BACKGROUND Malabsorptive bariatric surgery,including Roux-en-Y gastric bypass and duodenal switch,are known to be more metabolically effective than restrictive surgery.However,the permanent alteration of gastrointesti...BACKGROUND Malabsorptive bariatric surgery,including Roux-en-Y gastric bypass and duodenal switch,are known to be more metabolically effective than restrictive surgery.However,the permanent alteration of gastrointestinal anatomy from these operations has been shown to alter the kinetics of drug absorption and may make subsequent surgeries more technically challenging.AIM To evaluate perioperative liver transplant outcomes and rates of acute cellular rejection in recipients with prior malabsorptive bariatric surgery.METHODS Patients who underwent liver transplantation at a single institution between 2005-2024 with a history of malabsorptive bariatric surgery were identified.Matched controls were selected based on age,sex,listing model for end-stage liver disease(MELD),and primary liver diagnosis.RESULTS A total of 12 liver transplant patients with prior malabsorptive surgery and 25 controls were included.The mean age in the malabsorptive group was 50.5 years at the time of transplant and 92%were female.The mean MELD at the time of transplant was 27.6 and mean body mass index was 28.There were no significant differences in length of stay,post operative complications,or 1 year survival between the controls and malabsorptive patients.However,the malabsorptive group was significantly more likely to experience biopsy-proven and clinically treated acute cellular rejection than the controls(24%vs 66.7%,P=0.012),more frequent rejection episodes(0.28±0.53 vs 1.0±0.91,P=0.006),and earlier time to first rejection episode(P=0.002).CONCLUSION Previous malabsorptive bariatric surgery in liver transplant recipients did not increase the risk of perioperative complications or mortality but significantly increased the rate and frequency of acute cellular rejection.展开更多
Advancements in machine learning have revolutionized preoperative risk assessment.In this article,we comment on the article by Huang et al,which presents a recent multicenter cohort study demonstrated that machine lea...Advancements in machine learning have revolutionized preoperative risk assessment.In this article,we comment on the article by Huang et al,which presents a recent multicenter cohort study demonstrated that machine learning algorithms effectively stratify recurrence-free survival,providing a robust predictive framework for maximizing surgical outcomes in intrahepatic cholangiocarcinoma.By leveraging interpretable models,the research enhances clinical decision-making,allowing for more precise patient selection and personalized surgical strategies.These findings highlight the growing role of artificial intelligence in optimizing surgical outcomes and improving prognostic accuracy in hepatobiliary oncology.展开更多
This letter discusses the study by Liu et al recently published in World Journal of Psychiatry,which examines the benefits of combining epirubicin(EPI)with mindfulness interventions for patients with urinary system tu...This letter discusses the study by Liu et al recently published in World Journal of Psychiatry,which examines the benefits of combining epirubicin(EPI)with mindfulness interventions for patients with urinary system tumors and depre-ssion.The study included 110 patients and compared an experimental group receiving EPI and a mindfulness intervention strategy with a control group treated with mitomycin and standard care.Results showed that the experimental group had significant improvements in immune function,tumor markers,depression severity,quality of life,cancer-related fatigue,and nursing satisfac-tion.Despite acknowledging the study limitations such as a relatively small sample size and a short duration,the study highlights the efficacy of integrating mindfulness interventions into cancer treatment strategies to enhance patient outcomes and address psychological distress.展开更多
The brood-parasitic brown-headed cowbird(Molothrus ater)has one of the shortest incubation periods of any bird.Brown-headed cowbird eggs,and those of other avian brood parasites,tend to be more spherical due to their ...The brood-parasitic brown-headed cowbird(Molothrus ater)has one of the shortest incubation periods of any bird.Brown-headed cowbird eggs,and those of other avian brood parasites,tend to be more spherical due to their greater relative width.The traditional explanation for this egg shape is that it,combined with the thicker eggshells,resists host puncture-ejection.However,very few North American hosts of the brownheaded cowbird actually engage in puncture-ejection and therefore wider eggs may instead provide greater contact with a host’s brood patch during incubation,especially in large host nests.We tested whether greater egg width increased mean temperature and reduced temperature variation in brown-headed cowbirds by inserting temperature probes into brown-headed cowbird and house sparrow(Passer domesticus)eggs and placing them into red-winged blackbird(Agelaius phoeniceus)nests.House sparrow eggs are similar in appearance and in length to cowbird eggs,but are not as wide.We found no signifcant relationship between brown-headed cowbird egg width and mean incubation temperature.However,brown-headed cowbird eggs experienced less temperature variation than house sparrow eggs,and within brown-headed cowbird eggs,more spherical eggs experienced less temperature variation when accounting for differences in width.These results suggest that brownheaded cowbirds may have short incubation periods in part because their eggs exhibit less temperature variation over the course of incubation.The brown-headed cowbird’s egg shape may contribute to its accelerated embryonic development rate relative to host eggs of similar size,which explains its ability to hatch in a variety of host nests.展开更多
Oats, frequently incorporated into skincare formulations for their anti-inflammatory, moisturizing, and barrier-repairing properties, may present an overlooked risk to individuals with celiac disease, particularly whe...Oats, frequently incorporated into skincare formulations for their anti-inflammatory, moisturizing, and barrier-repairing properties, may present an overlooked risk to individuals with celiac disease, particularly when applied to compromised skin. Although pure oats are inherently gluten-free, the widespread contamination with gluten-containing grains like wheat, barley, or rye during agricultural and processing stages introduces the potential for gluten exposure through topical application. This raises important questions about whether gluten proteins, when applied to damaged skin, might penetrate the epidermal barrier and contribute to immune responses in genetically predisposed celiac patients, given that even minute amounts of gluten can trigger systemic symptoms. Emerging evidence suggests that transdermal absorption of gluten peptides through impaired skin integrity might bypass the gastrointestinal route, yet the precise mechanisms and clinical significance of this pathway remain poorly understood. The role of compromised skin in facilitating gluten absorption and the possible activation of CD4+ T-cells, mimicking gastrointestinal pathways, warrants further investigation. Additionally, the ability of gluten peptides to reach deeper dermal layers and potentially enter the systemic circulation remains speculative, though theoretically possible in severely disrupted skin barriers. Without clinical and molecular studies to determine the risk of topical gluten exposure, particularly in celiac patients with skin injuries, there remains a potential for undetected immune activation and subsequent adverse health outcomes in this sensitive population.展开更多
Due to the high water content in warm frozen soil,the pore water pressure and pore ice pressure generated within the sample during loading significantlyinfluencethe deformation and strength of the soil skeleton.Theref...Due to the high water content in warm frozen soil,the pore water pressure and pore ice pressure generated within the sample during loading significantlyinfluencethe deformation and strength of the soil skeleton.Therefore,it is essential to develop a constitutive model for warm frozen soil that can capture the changes in ice pressure and water pressure.This study introduces a macro-meso constitutive model based on a binary-medium framework to describe the mechanical behavior of warm frozen soil.In this model,warm frozen soil is conceptualized as consisting of bonded and frictional elements from a meso perspective.The bonded elements are modeled using a macro-meso elastic constitutive approach based on poromechanics,while the frictional elements employ a macro-meso elastoplastic approach,also grounded in poromechanics.These two elements are then linked within the binarymedium model framework.By replicating the experimental curves of warm frozen soils,the theoretical results from the proposed model show excellent agreement with experimental data.This consistency indicates that the model effectively simulates the strain softening and volumetric expansion behaviors of warm frozen soil samples under various conditions.Additionally,the constitutive model predicts changes in unfrozen water pressure,frozen temperature,unfrozen water saturation,and porosity during the loading process of warm frozen soil samples.展开更多
Fires,including wildfires,harm air quality and essential public services like transportation,communication,and utilities.These fires can also influence atmospheric conditions,including temperature and aerosols,potenti...Fires,including wildfires,harm air quality and essential public services like transportation,communication,and utilities.These fires can also influence atmospheric conditions,including temperature and aerosols,potentially affecting severe convective storms.Here,we investigate the remote impacts of fires in the western United States(WUS)on the occurrence of large hail(size:≥2.54 cm)in the central US(CUS)over the 20-year period of 2001–20 using the machine learning(ML),Random Forest(RF),and Extreme Gradient Boosting(XGB)methods.The developed RF and XGB models demonstrate high accuracy(>90%)and F1 scores of up to 0.78 in predicting large hail occurrences when WUS fires and CUS hailstorms coincide,particularly in four states(Wyoming,South Dakota,Nebraska,and Kansas).The key contributing variables identified from both ML models include the meteorological variables in the fire region(temperature and moisture),the westerly wind over the plume transport path,and the fire features(i.e.,the maximum fire power and burned area).The results confirm a linkage between WUS fires and severe weather in the CUS,corroborating the findings of our previous modeling study conducted on case simulations with a detailed physics model.展开更多
Background The effect of microbial phytase on amino acid and energy digestibility is not consistent in pigs,which may be related to the phytase dosage or the adaptation length to the diet.Therefore,an experiment was c...Background The effect of microbial phytase on amino acid and energy digestibility is not consistent in pigs,which may be related to the phytase dosage or the adaptation length to the diet.Therefore,an experiment was conducted to test the hypotheses that increasing dietary phytase after an 18-day adaptation period:1)increases nutrient and energy digestibility;2)increases plasma P,plasma inositol,and bone ash of young pigs;and 3)demonstrates that maximum phytate degradation requires more phytase than maximum P digestibility.Results Data indicated that increasing inclusion of phytase[0,250,500,1,000,2,000,and 4,000 phytase units(FTU)/kg feed]in corn-soybean meal-based diets increased apparent ileal digestibility(AID)of Trp(quadratic;P<0.05),and of Lys and Thr(linear;P<0.05),and tended to increase AID of Met(linear;P<0.10).Increasing dietary phytase also increased AID and apparent total tract digestibility(ATTD)of Ca and P(quadratic;P<0.05)and increased ATTD of K and Na(linear;P<0.05),but phytase did not influence the ATTD of Mg or gross energy.Concentrations of plasma P and bone ash increased(quadratic;P<0.05),and plasma inositol also increased(linear;P<0.05)with increasing inclusion of phytase.Reduced concentrations of inositol phosphate(IP)6 and IP5(quadratic;P<0.05),reduced IP4 and IP3(linear;P<0.05),but increased inositol concentrations(linear;P<0.05)were observed in ileal digesta as dietary phytase increased.The ATTD of P was maximized if at least 1,200 FTU/kg were used,whereas more than 4,000 FTU/kg were needed to maximize inositol release.Conclusions Increasing dietary levels of phytase after an 18-day adaptation period increased phytate and IP ester degradation and inositol release in the small intestine.Consequently,increasing dietary phytase resulted in improved digestibility of Ca,P,K,Na,and the first 4 limiting amino acids,and in increased concentrations of bone ash and plasma P and inositol.In a corn-soybean meal diet,maximum inositol release requires approximately 3,200 FTU/kg more phytase than that required for maximum P digestibility.展开更多
Background Reduction of the particle size of corn increases energy digestibility and concentrations of digestible and metabolizable energy.Pelleting may also reduce particle size of grain,but it is not known if there ...Background Reduction of the particle size of corn increases energy digestibility and concentrations of digestible and metabolizable energy.Pelleting may also reduce particle size of grain,but it is not known if there are interactions between particle size reduction and pelleting.The objective of this experiment was to test the hypothesis that particle size reduction and pelleting,separately or in combination,increase N balance,apparent total tract digestibility(ATTD)of fiber and fat,and net energy(NE)in corn-soybean meal diets fed to group-housed pigs.Methods Six corn-soybean meal-based diets were used in a 3×2 factorial design with 3 particle sizes of corn(i.e.,700,500,or 300μm)and 2 diet forms(i.e.,meal or pelleted).Pigs were allowed ad libitum access to feed and water.Twenty-four castrated male pigs(initial weight:29.52 kg;standard diviation:1.40)were allotted to the 6 diets using a 6×6 Latin square design with 6 calorimeter chambers(i.e.,4 pigs/chamber)and 6 periods.Oxygen consumption and CO_(2)and CH_(4)productions were measured during fed and fasting states and fecal and urine samples were collected.Results Regardless of particle size of corn,the ATTD of gross energy(GE),N,and acid-hydrolyzed ether extract(AEE),and the concentration of NE were greater(P<0.05)in pelleted diets than in meal diets.Regardless of diet form,the ATTD of GE,N,and AEE,and the concentration of NE were increased(linear;P<0.05)by reducing the particle size of corn,but the increase was greater in meal diets than in pelleted diets(interaction;P<0.05).Conclusions Both pelleting and reduction of corn particle size increased nutrient digestibility and NE,but increases were greater in meal diets than in pelleted diets.展开更多
BACKGROUND Fecal incontinence(FI)is an involuntary passage of fecal matter which can have a significant impact on a patient’s quality of life.Many modalities of treatment exist for FI.Sacral nerve stimulation is a we...BACKGROUND Fecal incontinence(FI)is an involuntary passage of fecal matter which can have a significant impact on a patient’s quality of life.Many modalities of treatment exist for FI.Sacral nerve stimulation is a well-established treatment for FI.Given the increased need of magnetic resonance imaging(MRI)for diagnostics,the In-terStim which was previously used in sacral nerve stimulation was limited by MRI incompatibility.Medtronic MRI-compatible InterStim was approved by the United States Food and Drug Administration in August 2020 and has been widely used.AIM To evaluate the efficacy,outcomes and complications of the MRI-compatible InterStim.METHODS Data of patients who underwent MRI-compatible Medtronic InterStim placement at UPMC Williamsport,University of Minnesota,Advocate Lutheran General Hospital,and University of Wisconsin-Madison was pooled and analyzed.Patient demographics,clinical features,surgical techniques,complications,and outcomes were analyzed.Strengthening the Reporting of Observational studies in Epidemiology(STROBE)cross-sectional reporting guidelines were used.RESULTS Seventy-three patients had the InterStim implanted.The mean age was 63.29±12.2 years.Fifty-seven(78.1%)patients were females and forty-two(57.5%)patients had diabetes.In addition to incontinence,overlapping symptoms included diarrhea(23.3%),fecal urgency(58.9%),and urinary incontinence(28.8%).Fifteen(20.5%)patients underwent Peripheral Nerve Evaluation before proceeding to definite implant placement.Thirty-two(43.8%)patients underwent rechargeable InterStim placement.Three(4.1%)patients needed removal of the implant.Migration of the external lead connection was observed in 7(9.6%)patients after the stage I procedure.The explanation for one patient was due to infection.Seven(9.6%)patients had other complications like nerve pain,hematoma,infection,lead fracture,and bleeding.The mean follow-up was 6.62±3.5 mo.Sixty-eight(93.2%)patients reported significant improvement of symptoms on follow-up evaluation.CONCLUSION This study shows promising results with significant symptom improvement,good efficacy and good patient outcomes with low complication rates while using MRI compatible InterStim for FI.Further long-term follow-up and future studies with a larger patient population is recommended.展开更多
Arroyo Verde epithermal deposit,in the North Patagonia region of Argentina,is located within the Lower Chon Aike volcanism and is developed between 192.6±2.5 Ma(mineralization host rock)and 189.5±2.6 Ma(over...Arroyo Verde epithermal deposit,in the North Patagonia region of Argentina,is located within the Lower Chon Aike volcanism and is developed between 192.6±2.5 Ma(mineralization host rock)and 189.5±2.6 Ma(overlying lava).Marifil volcanic complex is the host rock for these veins,veinlets and breccias.This particular small deposit has developed low to intermediate sulphidation characteristics,with gangue mineral textures associated with several ore minerals.Electron probe microanalysis determines electrum,silver minerals such as acanthite,and tetrahedrite,related Ag-Cu minerals like jalpaite,mckinstryite,stromeyerite,and base metals like chalcopyrite,sphalerite,galena and pyrite.Fluid inclusions in quartz of two out of five events indicate that these Low Jurassic veins were formed due to subtle boiling and dilution mechanisms and by low-salinity(3.4 wt.%to 6.7 wt.%NaCl Eq)magmatic-hydrothermal fluid at 225 to 310℃.The fluid inclusion measurements that indicate boiling(Event 3)were plotted,and based on this data,we interpret that the Arroyo Verde deposit has been eroded between 550 and 700 m.This particular character has not been previously recorded for other sectors of the eastern north Patagonian region.展开更多
Diabetic foot(DF)is a major public health concern.As evident from numerous previous studies,supervision of DF ulcer(DFU)is crucial,and a specific quality check-up is needed.Patients should be educated about glycaemic ...Diabetic foot(DF)is a major public health concern.As evident from numerous previous studies,supervision of DF ulcer(DFU)is crucial,and a specific quality check-up is needed.Patients should be educated about glycaemic management,DFUs,foot lesions,proper care for injuries,diet,and surgery.Certain reasonably priced treatments,such as hyperbaric oxygen and vacuum-assisted closure therapy,are also available for DFUs,along with modern wound care products and techniques.Nonetheless,DF care(cleaning,applying antimicrobial cream when wounded,and foot reflexology),blood glucose monitoring to control diabetes,and monthly or quarterly examinations in individuals with diabetes are effective in managing DFUs.Between 50%and 80%of DF infections are preventable.Regardless of the intensity of the lesion,it needs to be treated carefully and checked daily during infection.Tissue regeneration can be aided by cleaning,dressing,and application of topical medicines.The choice of shoes is also important because it affects blood circulation and nerve impulses.In general,regular check-ups,monitoring of the patient’s condition,measuring blood glucose levels,and providing frequent guidance regarding DFU care are crucial.Finally,this important clinical problem requires involvement of multiple professionals to properly manage it.展开更多
Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understan...Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understanding the underlying disease-causing mechanisms and building solutions that have implications for a broad spectrum of patients. One potential solution is to develop personalized medicine approaches based on strategies that target the most prevalent cellular events that are perturbed in patients. Especially in patients with a known genetic mutation, it may be possible to understand how these mutations contribute to problems that lead to neurodegeneration. Protein–protein interaction analyses offer great advantages for revealing how proteins interact, which cellular events are primarily involved in these interactions, and how they become affected when key genes are mutated in patients. This line of investigation also suggests novel druggable targets for patients with different mutations. Here, we focus on alsin and spastin, two proteins that are identified as “causative” for amyotrophic lateral sclerosis and hereditary spastic paraplegia, respectively, when mutated. Our review analyzes the protein interactome for alsin and spastin, the canonical pathways that are primarily important for each protein domain, as well as compounds that are either Food and Drug Administration–approved or are in active clinical trials concerning the affected cellular pathways. This line of research begins to pave the way for personalized medicine approaches that are desperately needed for rare neurodegenerative diseases that are complex and heterogeneous.展开更多
Background:The prevalence,age of onset,and symptomatology of traumatic brain injury,stroke,and neurodegenerative diseases(such as Alzheimer’s disease(AD),Parkinson’s disease,amyotrophic lateral sclerosis,and Hunting...Background:The prevalence,age of onset,and symptomatology of traumatic brain injury,stroke,and neurodegenerative diseases(such as Alzheimer’s disease(AD),Parkinson’s disease,amyotrophic lateral sclerosis,and Huntington’s disease)differ substantially between males and females.The higher prevalence of these brain disorders has been attributed to females having a greater longevity compared with males.Since one of the greatest risk factors of acquired brain injury(such as stroke,traumatic brain injury caused by fall)and neurodegenerative disease is age.展开更多
Axonal degeneration underlies many debilitating diseases including hereditary spastic paraplegia(HSP),a genetically and clinically diverse group of disorders characterized by spasticity and weakness of the lower extre...Axonal degeneration underlies many debilitating diseases including hereditary spastic paraplegia(HSP),a genetically and clinically diverse group of disorders characterized by spasticity and weakness of the lower extremities.HSP is one significant cause of chronic neurodisability due to the lack of effective treatments and a wide range of onset ages from early childhood to 70 years.展开更多
Human spinal cord organoids(hSCOs)offer a promising platform to study neurotrauma by addressing many limitations of traditional research models.These organoids provide access to human-specific physiological and geneti...Human spinal cord organoids(hSCOs)offer a promising platform to study neurotrauma by addressing many limitations of traditional research models.These organoids provide access to human-specific physiological and genetic mechanisms and can be derived from an individual's somatic cells(e.g.,blood or skin).This enables patient-specific paradigms for precision neurotrauma research,pa rticula rly relevant to the over 300,000 people in the United States living with chronic effects of spinal cord injury(SCI).展开更多
Cardiovascular disease remains the leading global cause of mortality,projected to increase by 73.4%from 2025 to 2050 despite declining age-standardized rates.Contemporary interventions,such as percutaneous coronary in...Cardiovascular disease remains the leading global cause of mortality,projected to increase by 73.4%from 2025 to 2050 despite declining age-standardized rates.Contemporary interventions,such as percutaneous coronary intervention and statins,reduce major adverse cardiovascular events(MACE)by 25%-30%,yet a 20%five-year MACE risk persists in high-risk cohorts.These approaches,histor-ically focused on luminal stenosis,fail to address systemic atherogenesis drivers like endothelial dysfunction and inflammation.Specifically,dietary linoleic acid restriction(<5 g/day)reduces oxidized low-density lipoprotein by approximately 15%by limiting peroxidation-prone bisallylic bonds,mitigating arterial inflam-mation,a key atherogenic trigger.Enhanced external counterpulsation,through pulsatile shear stress,enhances nitric oxide-mediated coronary perfusion,alle-viating angina in approximately 70%of refractory cases unresponsive to revascu-larization.Nanoparticle-facilitated chelation targets atherosclerotic plaques with precision,reducing calcium content by up to 30%in preclinical models,offering a novel avenue for lesion reversal.These innovations collectively address residual risk by tackling root causes,oxidative stress,endothelial dysfunction,and plaque instability,potentially halving MACE rates with widespread adoption.Despite promising preliminary data,gaps remain in long-term safety and scalability.Robust clinical trials are needed to validate these approaches,which collectively aim to transform cardiovascular disease management by prioritizing prevention and vascular restoration,potentially reducing coronary events to a public health rarity.展开更多
BACKGROUND Pelvic squamous cell carcinoma of unknown primary(CUP)is extremely rare,accounting for less than one percent of all CUP cases,and its infrequency has lim-ited the development of standardized diagnostic and ...BACKGROUND Pelvic squamous cell carcinoma of unknown primary(CUP)is extremely rare,accounting for less than one percent of all CUP cases,and its infrequency has lim-ited the development of standardized diagnostic and treatment guidelines.CASE SUMMARY A 77-year-old female with a history of resected lung adenocarcinoma presented with worsening constipation.Imaging revealed a 2.5 cm mass adjacent to the right levator ani muscle.Biopsy confirmed poorly differentiated squamous cell carcinoma,positive for pancytokeratin and p40,and negative for p16,cytokeratin 7,cytokeratin 20,and neuroendocrine markers.No primary lesion was identified despite extensive evaluation.She underwent five cycles of 5-fluorouracil(1000 mg/m^(2) continuous infusion,days 1-4)and mitomycin-C(10 mg/m^(2) on day 1)with concurrent pelvic radiotherapy(50.4 Gy in 28 fractions).Follow-up imaging demonstrated complete remission sustained for 12 months.Electrocorticography performance status improved from 2 at diagnosis to 1 during follow-up.CONCLUSION This case highlights the potential role of chemoradiotherapy in managing pelvic squamous cell CUP,achieving durable remission in selected patients.展开更多
Protein aggregates,mitochondrial import stress and neurodegenerative disorders:A salient hallmark of several neurodegenerative diseases,including Parkinson’s disease,is the abundance of protein aggregates(Goiran et a...Protein aggregates,mitochondrial import stress and neurodegenerative disorders:A salient hallmark of several neurodegenerative diseases,including Parkinson’s disease,is the abundance of protein aggregates(Goiran et al.,2022).This molecular event is believed to lead to activation of stress pathways ultimately resulting in cellular dysfunction(Eldeeb et al.,2022).Accordingly,many lines of research investigations focused on dampening the formation of protein aggregates or augmenting the clearance of protein aggregates as a potential therapeutic strategy to counteract the progression of neurodegenerative diseases,albeit with little success(Costa-Mattioli and Walter,2020).Cell stress cues such as the accumulation of protein aggregates lead to the activation of stress response pathways that aid cells in responding to the damage.Despite the notion that the transient activation of these pathways helps cells cope with stressors,persistent activation can induce unwanted apoptosis of cells and reduce overall tissue strength as well as lead to an accumulation of aggregation-prone proteins(Hetz and Papa,2018).Mutations in proteins involved in stress signaling termination can cause conditions like ataxia and early-onset dementia(Conroy et al.,2014).Therefore,it is crucial for stress response signaling to be turned off once conditions have improved.Nevertheless,the mechanisms by which cells silence these signals are still elusive.展开更多
文摘BACKGROUND Malabsorptive bariatric surgery,including Roux-en-Y gastric bypass and duodenal switch,are known to be more metabolically effective than restrictive surgery.However,the permanent alteration of gastrointestinal anatomy from these operations has been shown to alter the kinetics of drug absorption and may make subsequent surgeries more technically challenging.AIM To evaluate perioperative liver transplant outcomes and rates of acute cellular rejection in recipients with prior malabsorptive bariatric surgery.METHODS Patients who underwent liver transplantation at a single institution between 2005-2024 with a history of malabsorptive bariatric surgery were identified.Matched controls were selected based on age,sex,listing model for end-stage liver disease(MELD),and primary liver diagnosis.RESULTS A total of 12 liver transplant patients with prior malabsorptive surgery and 25 controls were included.The mean age in the malabsorptive group was 50.5 years at the time of transplant and 92%were female.The mean MELD at the time of transplant was 27.6 and mean body mass index was 28.There were no significant differences in length of stay,post operative complications,or 1 year survival between the controls and malabsorptive patients.However,the malabsorptive group was significantly more likely to experience biopsy-proven and clinically treated acute cellular rejection than the controls(24%vs 66.7%,P=0.012),more frequent rejection episodes(0.28±0.53 vs 1.0±0.91,P=0.006),and earlier time to first rejection episode(P=0.002).CONCLUSION Previous malabsorptive bariatric surgery in liver transplant recipients did not increase the risk of perioperative complications or mortality but significantly increased the rate and frequency of acute cellular rejection.
文摘Advancements in machine learning have revolutionized preoperative risk assessment.In this article,we comment on the article by Huang et al,which presents a recent multicenter cohort study demonstrated that machine learning algorithms effectively stratify recurrence-free survival,providing a robust predictive framework for maximizing surgical outcomes in intrahepatic cholangiocarcinoma.By leveraging interpretable models,the research enhances clinical decision-making,allowing for more precise patient selection and personalized surgical strategies.These findings highlight the growing role of artificial intelligence in optimizing surgical outcomes and improving prognostic accuracy in hepatobiliary oncology.
文摘This letter discusses the study by Liu et al recently published in World Journal of Psychiatry,which examines the benefits of combining epirubicin(EPI)with mindfulness interventions for patients with urinary system tumors and depre-ssion.The study included 110 patients and compared an experimental group receiving EPI and a mindfulness intervention strategy with a control group treated with mitomycin and standard care.Results showed that the experimental group had significant improvements in immune function,tumor markers,depression severity,quality of life,cancer-related fatigue,and nursing satisfac-tion.Despite acknowledging the study limitations such as a relatively small sample size and a short duration,the study highlights the efficacy of integrating mindfulness interventions into cancer treatment strategies to enhance patient outcomes and address psychological distress.
文摘The brood-parasitic brown-headed cowbird(Molothrus ater)has one of the shortest incubation periods of any bird.Brown-headed cowbird eggs,and those of other avian brood parasites,tend to be more spherical due to their greater relative width.The traditional explanation for this egg shape is that it,combined with the thicker eggshells,resists host puncture-ejection.However,very few North American hosts of the brownheaded cowbird actually engage in puncture-ejection and therefore wider eggs may instead provide greater contact with a host’s brood patch during incubation,especially in large host nests.We tested whether greater egg width increased mean temperature and reduced temperature variation in brown-headed cowbirds by inserting temperature probes into brown-headed cowbird and house sparrow(Passer domesticus)eggs and placing them into red-winged blackbird(Agelaius phoeniceus)nests.House sparrow eggs are similar in appearance and in length to cowbird eggs,but are not as wide.We found no signifcant relationship between brown-headed cowbird egg width and mean incubation temperature.However,brown-headed cowbird eggs experienced less temperature variation than house sparrow eggs,and within brown-headed cowbird eggs,more spherical eggs experienced less temperature variation when accounting for differences in width.These results suggest that brownheaded cowbirds may have short incubation periods in part because their eggs exhibit less temperature variation over the course of incubation.The brown-headed cowbird’s egg shape may contribute to its accelerated embryonic development rate relative to host eggs of similar size,which explains its ability to hatch in a variety of host nests.
文摘Oats, frequently incorporated into skincare formulations for their anti-inflammatory, moisturizing, and barrier-repairing properties, may present an overlooked risk to individuals with celiac disease, particularly when applied to compromised skin. Although pure oats are inherently gluten-free, the widespread contamination with gluten-containing grains like wheat, barley, or rye during agricultural and processing stages introduces the potential for gluten exposure through topical application. This raises important questions about whether gluten proteins, when applied to damaged skin, might penetrate the epidermal barrier and contribute to immune responses in genetically predisposed celiac patients, given that even minute amounts of gluten can trigger systemic symptoms. Emerging evidence suggests that transdermal absorption of gluten peptides through impaired skin integrity might bypass the gastrointestinal route, yet the precise mechanisms and clinical significance of this pathway remain poorly understood. The role of compromised skin in facilitating gluten absorption and the possible activation of CD4+ T-cells, mimicking gastrointestinal pathways, warrants further investigation. Additionally, the ability of gluten peptides to reach deeper dermal layers and potentially enter the systemic circulation remains speculative, though theoretically possible in severely disrupted skin barriers. Without clinical and molecular studies to determine the risk of topical gluten exposure, particularly in celiac patients with skin injuries, there remains a potential for undetected immune activation and subsequent adverse health outcomes in this sensitive population.
基金the financial support from the funding of the National Natural Science Foundation of China(NSFC)(Grant Nos.42401160 and U22A20596)the Science and Technology Plan Project of Linzhi(Grant No.SYQ2024-13).
文摘Due to the high water content in warm frozen soil,the pore water pressure and pore ice pressure generated within the sample during loading significantlyinfluencethe deformation and strength of the soil skeleton.Therefore,it is essential to develop a constitutive model for warm frozen soil that can capture the changes in ice pressure and water pressure.This study introduces a macro-meso constitutive model based on a binary-medium framework to describe the mechanical behavior of warm frozen soil.In this model,warm frozen soil is conceptualized as consisting of bonded and frictional elements from a meso perspective.The bonded elements are modeled using a macro-meso elastic constitutive approach based on poromechanics,while the frictional elements employ a macro-meso elastoplastic approach,also grounded in poromechanics.These two elements are then linked within the binarymedium model framework.By replicating the experimental curves of warm frozen soils,the theoretical results from the proposed model show excellent agreement with experimental data.This consistency indicates that the model effectively simulates the strain softening and volumetric expansion behaviors of warm frozen soil samples under various conditions.Additionally,the constitutive model predicts changes in unfrozen water pressure,frozen temperature,unfrozen water saturation,and porosity during the loading process of warm frozen soil samples.
基金supported by the U.S.Department of Energy,Office of Science,Office of Biological and Environmental Research program as part of the Regional and Global Model Analysis and Multi-Sector Dynamics program areas(Award Number DE-SC0016605)Argonne National Laboratory is operated for the DOE by UChicago Argonne,LLC,under contract DE-AC02-06CH11357+1 种基金the National Energy Research Scientific Computing Center(NERSC)NERSC is a U.S.DOE Office of Science User Facility operated under Contract DE-AC02-05CH11231.
文摘Fires,including wildfires,harm air quality and essential public services like transportation,communication,and utilities.These fires can also influence atmospheric conditions,including temperature and aerosols,potentially affecting severe convective storms.Here,we investigate the remote impacts of fires in the western United States(WUS)on the occurrence of large hail(size:≥2.54 cm)in the central US(CUS)over the 20-year period of 2001–20 using the machine learning(ML),Random Forest(RF),and Extreme Gradient Boosting(XGB)methods.The developed RF and XGB models demonstrate high accuracy(>90%)and F1 scores of up to 0.78 in predicting large hail occurrences when WUS fires and CUS hailstorms coincide,particularly in four states(Wyoming,South Dakota,Nebraska,and Kansas).The key contributing variables identified from both ML models include the meteorological variables in the fire region(temperature and moisture),the westerly wind over the plume transport path,and the fire features(i.e.,the maximum fire power and burned area).The results confirm a linkage between WUS fires and severe weather in the CUS,corroborating the findings of our previous modeling study conducted on case simulations with a detailed physics model.
基金support for this research from AB Vista,Marlborough,UK,is greatly appreciated。
文摘Background The effect of microbial phytase on amino acid and energy digestibility is not consistent in pigs,which may be related to the phytase dosage or the adaptation length to the diet.Therefore,an experiment was conducted to test the hypotheses that increasing dietary phytase after an 18-day adaptation period:1)increases nutrient and energy digestibility;2)increases plasma P,plasma inositol,and bone ash of young pigs;and 3)demonstrates that maximum phytate degradation requires more phytase than maximum P digestibility.Results Data indicated that increasing inclusion of phytase[0,250,500,1,000,2,000,and 4,000 phytase units(FTU)/kg feed]in corn-soybean meal-based diets increased apparent ileal digestibility(AID)of Trp(quadratic;P<0.05),and of Lys and Thr(linear;P<0.05),and tended to increase AID of Met(linear;P<0.10).Increasing dietary phytase also increased AID and apparent total tract digestibility(ATTD)of Ca and P(quadratic;P<0.05)and increased ATTD of K and Na(linear;P<0.05),but phytase did not influence the ATTD of Mg or gross energy.Concentrations of plasma P and bone ash increased(quadratic;P<0.05),and plasma inositol also increased(linear;P<0.05)with increasing inclusion of phytase.Reduced concentrations of inositol phosphate(IP)6 and IP5(quadratic;P<0.05),reduced IP4 and IP3(linear;P<0.05),but increased inositol concentrations(linear;P<0.05)were observed in ileal digesta as dietary phytase increased.The ATTD of P was maximized if at least 1,200 FTU/kg were used,whereas more than 4,000 FTU/kg were needed to maximize inositol release.Conclusions Increasing dietary levels of phytase after an 18-day adaptation period increased phytate and IP ester degradation and inositol release in the small intestine.Consequently,increasing dietary phytase resulted in improved digestibility of Ca,P,K,Na,and the first 4 limiting amino acids,and in increased concentrations of bone ash and plasma P and inositol.In a corn-soybean meal diet,maximum inositol release requires approximately 3,200 FTU/kg more phytase than that required for maximum P digestibility.
基金The financial support from the National Pork Board,Des Moines,IA,USA,is greatly appreciated。
文摘Background Reduction of the particle size of corn increases energy digestibility and concentrations of digestible and metabolizable energy.Pelleting may also reduce particle size of grain,but it is not known if there are interactions between particle size reduction and pelleting.The objective of this experiment was to test the hypothesis that particle size reduction and pelleting,separately or in combination,increase N balance,apparent total tract digestibility(ATTD)of fiber and fat,and net energy(NE)in corn-soybean meal diets fed to group-housed pigs.Methods Six corn-soybean meal-based diets were used in a 3×2 factorial design with 3 particle sizes of corn(i.e.,700,500,or 300μm)and 2 diet forms(i.e.,meal or pelleted).Pigs were allowed ad libitum access to feed and water.Twenty-four castrated male pigs(initial weight:29.52 kg;standard diviation:1.40)were allotted to the 6 diets using a 6×6 Latin square design with 6 calorimeter chambers(i.e.,4 pigs/chamber)and 6 periods.Oxygen consumption and CO_(2)and CH_(4)productions were measured during fed and fasting states and fecal and urine samples were collected.Results Regardless of particle size of corn,the ATTD of gross energy(GE),N,and acid-hydrolyzed ether extract(AEE),and the concentration of NE were greater(P<0.05)in pelleted diets than in meal diets.Regardless of diet form,the ATTD of GE,N,and AEE,and the concentration of NE were increased(linear;P<0.05)by reducing the particle size of corn,but the increase was greater in meal diets than in pelleted diets(interaction;P<0.05).Conclusions Both pelleting and reduction of corn particle size increased nutrient digestibility and NE,but increases were greater in meal diets than in pelleted diets.
文摘BACKGROUND Fecal incontinence(FI)is an involuntary passage of fecal matter which can have a significant impact on a patient’s quality of life.Many modalities of treatment exist for FI.Sacral nerve stimulation is a well-established treatment for FI.Given the increased need of magnetic resonance imaging(MRI)for diagnostics,the In-terStim which was previously used in sacral nerve stimulation was limited by MRI incompatibility.Medtronic MRI-compatible InterStim was approved by the United States Food and Drug Administration in August 2020 and has been widely used.AIM To evaluate the efficacy,outcomes and complications of the MRI-compatible InterStim.METHODS Data of patients who underwent MRI-compatible Medtronic InterStim placement at UPMC Williamsport,University of Minnesota,Advocate Lutheran General Hospital,and University of Wisconsin-Madison was pooled and analyzed.Patient demographics,clinical features,surgical techniques,complications,and outcomes were analyzed.Strengthening the Reporting of Observational studies in Epidemiology(STROBE)cross-sectional reporting guidelines were used.RESULTS Seventy-three patients had the InterStim implanted.The mean age was 63.29±12.2 years.Fifty-seven(78.1%)patients were females and forty-two(57.5%)patients had diabetes.In addition to incontinence,overlapping symptoms included diarrhea(23.3%),fecal urgency(58.9%),and urinary incontinence(28.8%).Fifteen(20.5%)patients underwent Peripheral Nerve Evaluation before proceeding to definite implant placement.Thirty-two(43.8%)patients underwent rechargeable InterStim placement.Three(4.1%)patients needed removal of the implant.Migration of the external lead connection was observed in 7(9.6%)patients after the stage I procedure.The explanation for one patient was due to infection.Seven(9.6%)patients had other complications like nerve pain,hematoma,infection,lead fracture,and bleeding.The mean follow-up was 6.62±3.5 mo.Sixty-eight(93.2%)patients reported significant improvement of symptoms on follow-up evaluation.CONCLUSION This study shows promising results with significant symptom improvement,good efficacy and good patient outcomes with low complication rates while using MRI compatible InterStim for FI.Further long-term follow-up and future studies with a larger patient population is recommended.
文摘Arroyo Verde epithermal deposit,in the North Patagonia region of Argentina,is located within the Lower Chon Aike volcanism and is developed between 192.6±2.5 Ma(mineralization host rock)and 189.5±2.6 Ma(overlying lava).Marifil volcanic complex is the host rock for these veins,veinlets and breccias.This particular small deposit has developed low to intermediate sulphidation characteristics,with gangue mineral textures associated with several ore minerals.Electron probe microanalysis determines electrum,silver minerals such as acanthite,and tetrahedrite,related Ag-Cu minerals like jalpaite,mckinstryite,stromeyerite,and base metals like chalcopyrite,sphalerite,galena and pyrite.Fluid inclusions in quartz of two out of five events indicate that these Low Jurassic veins were formed due to subtle boiling and dilution mechanisms and by low-salinity(3.4 wt.%to 6.7 wt.%NaCl Eq)magmatic-hydrothermal fluid at 225 to 310℃.The fluid inclusion measurements that indicate boiling(Event 3)were plotted,and based on this data,we interpret that the Arroyo Verde deposit has been eroded between 550 and 700 m.This particular character has not been previously recorded for other sectors of the eastern north Patagonian region.
基金Supported by the King Salman Center for Disability Research,No.KSRG-2023-407.
文摘Diabetic foot(DF)is a major public health concern.As evident from numerous previous studies,supervision of DF ulcer(DFU)is crucial,and a specific quality check-up is needed.Patients should be educated about glycaemic management,DFUs,foot lesions,proper care for injuries,diet,and surgery.Certain reasonably priced treatments,such as hyperbaric oxygen and vacuum-assisted closure therapy,are also available for DFUs,along with modern wound care products and techniques.Nonetheless,DF care(cleaning,applying antimicrobial cream when wounded,and foot reflexology),blood glucose monitoring to control diabetes,and monthly or quarterly examinations in individuals with diabetes are effective in managing DFUs.Between 50%and 80%of DF infections are preventable.Regardless of the intensity of the lesion,it needs to be treated carefully and checked daily during infection.Tissue regeneration can be aided by cleaning,dressing,and application of topical medicines.The choice of shoes is also important because it affects blood circulation and nerve impulses.In general,regular check-ups,monitoring of the patient’s condition,measuring blood glucose levels,and providing frequent guidance regarding DFU care are crucial.Finally,this important clinical problem requires involvement of multiple professionals to properly manage it.
基金funded by NIH-NIA R01AG061708 (to PHO)Patrick Grange Memorial Foundation (to PHO)+1 种基金A Long Swim (to PHO)CureSPG4 Foundation (to PHO)。
文摘Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understanding the underlying disease-causing mechanisms and building solutions that have implications for a broad spectrum of patients. One potential solution is to develop personalized medicine approaches based on strategies that target the most prevalent cellular events that are perturbed in patients. Especially in patients with a known genetic mutation, it may be possible to understand how these mutations contribute to problems that lead to neurodegeneration. Protein–protein interaction analyses offer great advantages for revealing how proteins interact, which cellular events are primarily involved in these interactions, and how they become affected when key genes are mutated in patients. This line of investigation also suggests novel druggable targets for patients with different mutations. Here, we focus on alsin and spastin, two proteins that are identified as “causative” for amyotrophic lateral sclerosis and hereditary spastic paraplegia, respectively, when mutated. Our review analyzes the protein interactome for alsin and spastin, the canonical pathways that are primarily important for each protein domain, as well as compounds that are either Food and Drug Administration–approved or are in active clinical trials concerning the affected cellular pathways. This line of research begins to pave the way for personalized medicine approaches that are desperately needed for rare neurodegenerative diseases that are complex and heterogeneous.
基金supported by NIH/NICHD RO1HD109157supported by his American Heart AssociationAward Career Development Award (932980)National Science Foundation CAREER award (NSF2401215)
文摘Background:The prevalence,age of onset,and symptomatology of traumatic brain injury,stroke,and neurodegenerative diseases(such as Alzheimer’s disease(AD),Parkinson’s disease,amyotrophic lateral sclerosis,and Huntington’s disease)differ substantially between males and females.The higher prevalence of these brain disorders has been attributed to females having a greater longevity compared with males.Since one of the greatest risk factors of acquired brain injury(such as stroke,traumatic brain injury caused by fall)and neurodegenerative disease is age.
基金supported by the NIH grant(RO1 NS118066)the Blazer Foundation(to XJL)。
文摘Axonal degeneration underlies many debilitating diseases including hereditary spastic paraplegia(HSP),a genetically and clinically diverse group of disorders characterized by spasticity and weakness of the lower extremities.HSP is one significant cause of chronic neurodisability due to the lack of effective treatments and a wide range of onset ages from early childhood to 70 years.
基金supported by the Belle Carnell Regenerative Neurorehabilitation Fundthe National Institutes of Health(R01NS113935 to CKF)。
文摘Human spinal cord organoids(hSCOs)offer a promising platform to study neurotrauma by addressing many limitations of traditional research models.These organoids provide access to human-specific physiological and genetic mechanisms and can be derived from an individual's somatic cells(e.g.,blood or skin).This enables patient-specific paradigms for precision neurotrauma research,pa rticula rly relevant to the over 300,000 people in the United States living with chronic effects of spinal cord injury(SCI).
文摘Cardiovascular disease remains the leading global cause of mortality,projected to increase by 73.4%from 2025 to 2050 despite declining age-standardized rates.Contemporary interventions,such as percutaneous coronary intervention and statins,reduce major adverse cardiovascular events(MACE)by 25%-30%,yet a 20%five-year MACE risk persists in high-risk cohorts.These approaches,histor-ically focused on luminal stenosis,fail to address systemic atherogenesis drivers like endothelial dysfunction and inflammation.Specifically,dietary linoleic acid restriction(<5 g/day)reduces oxidized low-density lipoprotein by approximately 15%by limiting peroxidation-prone bisallylic bonds,mitigating arterial inflam-mation,a key atherogenic trigger.Enhanced external counterpulsation,through pulsatile shear stress,enhances nitric oxide-mediated coronary perfusion,alle-viating angina in approximately 70%of refractory cases unresponsive to revascu-larization.Nanoparticle-facilitated chelation targets atherosclerotic plaques with precision,reducing calcium content by up to 30%in preclinical models,offering a novel avenue for lesion reversal.These innovations collectively address residual risk by tackling root causes,oxidative stress,endothelial dysfunction,and plaque instability,potentially halving MACE rates with widespread adoption.Despite promising preliminary data,gaps remain in long-term safety and scalability.Robust clinical trials are needed to validate these approaches,which collectively aim to transform cardiovascular disease management by prioritizing prevention and vascular restoration,potentially reducing coronary events to a public health rarity.
文摘BACKGROUND Pelvic squamous cell carcinoma of unknown primary(CUP)is extremely rare,accounting for less than one percent of all CUP cases,and its infrequency has lim-ited the development of standardized diagnostic and treatment guidelines.CASE SUMMARY A 77-year-old female with a history of resected lung adenocarcinoma presented with worsening constipation.Imaging revealed a 2.5 cm mass adjacent to the right levator ani muscle.Biopsy confirmed poorly differentiated squamous cell carcinoma,positive for pancytokeratin and p40,and negative for p16,cytokeratin 7,cytokeratin 20,and neuroendocrine markers.No primary lesion was identified despite extensive evaluation.She underwent five cycles of 5-fluorouracil(1000 mg/m^(2) continuous infusion,days 1-4)and mitomycin-C(10 mg/m^(2) on day 1)with concurrent pelvic radiotherapy(50.4 Gy in 28 fractions).Follow-up imaging demonstrated complete remission sustained for 12 months.Electrocorticography performance status improved from 2 at diagnosis to 1 during follow-up.CONCLUSION This case highlights the potential role of chemoradiotherapy in managing pelvic squamous cell CUP,achieving durable remission in selected patients.
文摘Protein aggregates,mitochondrial import stress and neurodegenerative disorders:A salient hallmark of several neurodegenerative diseases,including Parkinson’s disease,is the abundance of protein aggregates(Goiran et al.,2022).This molecular event is believed to lead to activation of stress pathways ultimately resulting in cellular dysfunction(Eldeeb et al.,2022).Accordingly,many lines of research investigations focused on dampening the formation of protein aggregates or augmenting the clearance of protein aggregates as a potential therapeutic strategy to counteract the progression of neurodegenerative diseases,albeit with little success(Costa-Mattioli and Walter,2020).Cell stress cues such as the accumulation of protein aggregates lead to the activation of stress response pathways that aid cells in responding to the damage.Despite the notion that the transient activation of these pathways helps cells cope with stressors,persistent activation can induce unwanted apoptosis of cells and reduce overall tissue strength as well as lead to an accumulation of aggregation-prone proteins(Hetz and Papa,2018).Mutations in proteins involved in stress signaling termination can cause conditions like ataxia and early-onset dementia(Conroy et al.,2014).Therefore,it is crucial for stress response signaling to be turned off once conditions have improved.Nevertheless,the mechanisms by which cells silence these signals are still elusive.
