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Liver transplantation as an alternative for the treatment of intrahepatic cholangiocarcinoma: Past, present, and future directions

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Hepatobiliary & Pancreatic Diseases International 2024年第2期23卷 129-138页

作者： Sudha Kodali Ashton A Connor Souhail Thabet Elizabeth W Brombosz R Mark Ghobrial Sherrie and Alan Conover Center for Liver Disease and Transplantation Houston Methodist HospitalHoustonTX 77030USA JC Walter Jr Transplant Center Houston Methodist HospitalHoustonTX 77030USA department of Medicine Weill Cornell Medical CollegeNew YorkNYUSA department of Surgery Houston Methodist HospitalHoustonTX 77030USA department of Surgery Weill Cornell Medical CollegeNew YorkNYUSA School of Medicine New Giza UniversityGizaEgypt

Intrahepatic cholangiocarcinoma(iCCA)is a rare biliary tract cancer with high mortality *** resection of the iCCA lesion is the first choice of treatment,with good prognosis after margin-negative ***,only 12%-40% of patients are eligible for resection at presentation due to cirrhosis,portal hypertension,or large tumor *** transplantation(LT)offers margin-negative iCCA extirpation for patients with unresectable ***,iCCA was a contraindication for LT until size-based selection criteria were introduced to identify patients with satisfied post-LT *** studies have shown that tumor biology-based selection can yield high post-LT survival in patients with locally advanced *** selection criterion is the tumor response to neoadjuvant *** with response to neoadjuvant therapy have better outcomes after LT compared with those without tumor response to neoadjuvant *** index that helps predict the treatment outcome is the *** survival outcomes have also opened the door for living donor LT for *** undergoing LT for iCCA now have statistically similar survival rates as patients undergoing *** combination of surgery and locoregional and systemic therapies improves the prognosis of iCCA patients.

关键词： Liver transplantation Cholangiocarcinoma Hepatectomy Transplant oncology Liver neoplasm

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Genome and clonal hematopoiesis stability contrasts with immune,cfDNA,mitochondrial,and telomere length changes during short duration spaceflight

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Precision Clinical Medicine 2024年第1期7卷 1-13页

作者： J.Sebastian Garcia-Medina Karolina Sienkiewicz S.Anand Narayanan Eliah G.Overbey Kirill Grigorev Krista A.Ryon Marissa Burke Jacqueline Proszynski Braden Tierney Caleb M.Schmidt Nuria Mencia-Trinchant Remi Klotz Veronica Ortiz Jonathan Foox Christopher Chin Deena Najjar Irina Matei Irenaeus Chan Carlos Cruchaga Ashley Kleinman JangKeun Kim Alexander Lucaci Conor Loy Omary Mzava Iwijn De Vlaminck Anvita Singaraju Lynn E.Taylor Julian C.Schmidt Michael A.Schmidt Kelly Blease Juan Moreno Andrew Boddicker Junhua Zhao Bryan Lajoie Andrew Altomare Semyon Kruglyak Shawn Levy Min Yu Duane C.Hassane Susan M.Bailey Kelly Bolton Jaime Mateus Christopher E.Mason department of physiology and biophysics Weill Cornell MedicineCornell UniversityNew YorkNY 10021USA The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine Weill Cornell MedicineNew YorkNY 10021USA department of Immunology Weill Cornell MedicineCornell UniversityNew YorkNY 10021USA department of Stem Cell Biology and Regenerative Medicine Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90033USA Space Exploration Technologies Corporation HawthomeCA 90250USA Sovaris Aerospace BoulderCO 80302USA Advanced Pattern Analysis&Human Performance Group BoulderCO 80302USA Children's Cancer and Blood Foundation Laboratories Departments of Pediatrics and Cell and Developmental BiologyDrukier Institute for Children's HealthMeyer Cancer CenterWeill Cornell MedicineNew YorkNY 10021USA Meyer Cancer Center Weill Cornell MedicineNew YorkNY 10065USA department of Nutrition and Integrative physiology Florida State UniversityTallahasseeFL 32306USA department of Systems Engineering Colorado State UniversityFort CollinsCO 80523USA Element Biosciences San DiegoCA 10055USA department of Environmental and Radiological Health Sciences Colorado State UniversityFort CollinsCO 80523USA Cell and Molecular Biology Program Colorado State UniversityFort CollinsCO 80523USA BioAstra Inc New YorkNYUSA Washington university.St Louis Oncology Division St.LouisMO 63100USA Meinig School of Biomedical Engineering Cornell UniversityIthacaNY 14853USA The Feil Family Brain and Mind Research Institute Weill Cornell MedicineNY 10021USA WorldQuant Initiative for Quantitative Prediction Weill Cornell MedicineNew YorkNY 10021USA

Background The Inspiration4(I4)mission,the first all-civilian orbital flight mission,investigated the physiological effects of short-duration spaceflight through a multi-omic *** advances,there remains much to learn about human adaptation to spaceflight's unique challenges,including microgravity,immune system perturbations,and radiation *** To provide a detailed genetics analysis of the mission,we collected dried blood spots pre-,during,and post-flight for DNA *** length was measured by quantitative PCR,while whole genome and cfDNA sequencing provided insight into genomic stability and immune adaptations.A robust bioinformatic pipeline was used for data analysis,including variant calling to assess mutational *** Telomere elongation occurred during spaceflight and shortened after return to ***-free DNA analysis revealed increased immune cell signatures *** significant clonal hematopoiesis of indeterminate potential(CHIP)or whole-genome instability was *** long-term gene expression changes across immune cells suggested cellular adaptations to the space environment persisting months *** Our findings provide valuable insights into the physiological consequences of short-duration spaceflight,with telomere dynamics and immune cell gene expression adapting to spaceflight and persisting after return to *** sequencing data will serve as a reference point for studying the early development of CHIP in astronauts,an understudied phenomenon as previous studies have focused on career *** study will serve as a reference point for future commercial and non-commercial spaceflight,low Earth orbit(LEO)missions,and deep-space exploration.

关键词： genomes clonal hematopoiesis stability immune mitochondria ribosomes spaceflight

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Skin neuropathy and immunomodulation in diseases

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Fundamental Research 2024年第2期4卷 218-225页

作者： Manze Zhang Tingting Liu Jing Yang department of Biology Stanford UniversityStanfordCA 94305USA department of Biochemistry Weill Cornell Medical CollegeNew YorkNY 10065USA IDG/McGovern Institute for Brain Research Center for Life SciencesSchool of Life SciencesPeking UniversityBeijing 100871China Peking university.Third Hospital Cancer Center Beijing 100191China

Skin is a vital barrier tissue of the *** responses in the skin must be precisely controlled,which would otherwise cause severe disease conditions such as psoriasis,atopic dermatitis,or pathogenic *** evidence has increasingly demonstrated the essential roles of neural innervations,i.e.,sensory and sympathetic signals,in modulating skin ***,neuropathic changes of such neural structures have been observed in skin disease conditions,implicating their direct involvement in various pathological *** in-depth understanding of the mechanism underlying skin neuropathy and its immunomodulatory effects could help reveal novel entry points for therapeutic ***,we summarize the neuroimmune interactions between neuropathic events and skin immunity,highlighting the current knowledge and future perspectives of this emerging research frontier.

关键词： Skin Neuropathy Neuroimmune Psoriasis Atopic dermatitis Pathogenic infection

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Clinical and socioeconomic determinants of survival in biliary tract adenocarcinomas

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1374-1383页

作者： Laura Sahyoun Kay Chen Cynthia Tsay George Chen Petr Protiva department of Gastroenterology and Hepatology Weill Cornell MedicineNew YorkNY 10065United States Gastroenterology Section Jennifer Moreno VA San Diego Healthcare SystemSan DiegoCA 92161United States Division of Gastroenterology Department of MedicineUniversity of California San DiegoLa JollaCA 92093United States department of Gastroenterology and Hepatology John Hopkins HospitalBaltimoreMD 21287United States department of Digestive Diseases Yale New Haven HospitalNew HavenCT 06520United States department of Gastroenterology VA Connecticut Health Care SystemWest HavenCT 06516United States

BACKGROUND Despite advances in detection and treatments,biliary tract cancers continue to have poor survival ***,there is limited data investigating the significance of socioeconomic status,race/ethnicity,and environmental factors in biliary tract cancer *** from the Surveillance,Epidemiology,and End Results database for biliary and gallbladder adenocarcinomas were extracted from 1975 to ***-conomic data included smoking,poverty level,education,adjusted household income,and percentage of foreign-born persons and urban *** was calculated with Cox proportional hazards models for death in the 5-year period following *** Our study included 15883 gallbladder,11466 intrahepatic biliary,12869 extrahepatic biliary and 7268 ampulla of Vater adenocarcinoma *** analyzing county-specific demographics,patients from counties with higher incomes were associated with higher survival rates[hazard ratio(HR)=0.97,Pcollege level education and counties with a higher urban population had higher 5-year survival rates(HR=0.96,P=0.002 and HR=0.97,P=0.004,respectively).CONCLUSION Worse survival outcomes were observed in lower income counties while higher income and education level were associated with higher 5-year overall survival among gallbladder and biliary malignancies.

关键词： Biliary tract cancers Survival Outcomes research Socioeconomic factors Healthcare disparities

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Rescue from complications after pancreaticoduodenectomies at a low-volume Caribbean center:Value of tailored peri-pancreatectomy protocols

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World Journal of Gastrointestinal Surgery 2024年第3期16卷 681-688页

作者： Shamir O Cawich Elijah Dixon Parul J Shukla Shailesh V Shrikhande Rahul R Deshpande Fawwaz Mohammed Neil W Pearce Wesley Francis Shaneeta Johnson Johann Bujhawan department of Surgery University of the West IndiesSt Augustine 000000Trinidad and Tobago department of Surgery Faculty of MedicineUniversity of CalgaryCalgaryAlberta T2N2T9Canada department of Surgery Weill Cornell Medical CollegeNew YorkNY 10065United States department of Surgical Oncology Tata Memorial CenterHomi Bhabha National UniversityMumbai 400012India department of Surgery Manchester Royal InfirmaryManchester M139WLUnited Kingdom university.Surgical Unit Southampton General HospitalSouthampton SO166YDUnited Kingdom department of Surgery University of the West IndiesNassau N-1184Bahamas department of Surgery Morehouse School of MedicineAtlantaGA 30310United States department of Surgery General Hospital in Port of SpainPort of Spain 000000Trinidad and Tobago

BACKGROUND Pancreaticoduodenectomy(PD)is a technically complex operation,with a re-latively high risk for *** ability to rescue patients from post-PD complications is as a recognized quality *** protocols were instituted at our low volume facility in the year *** To document the rate of rescue from post-PD complications with tailored protocols in place as a measure of *** A retrospective audit was performed to collect data from patients who experienced major post-PD complications at a low volume pancreatic surgery unit in Trinidad and Tobago between January 1,2013 and June 30,***-dardized definitions from the International Study Group of Pancreatic Surgery were used to define post-PD complications,and the modified Clavien-Dindo classification was used to classify post-PD *** Over the study period,113 patients at a mean age of 57.5 years(standard deviation[SD]±9.23;range:30-90;median:56)underwent PDs at this *** complications were recorded in 33(29.2%)patients at a mean age of 53.8 years(SD:±7.9).Twenty-nine(87.9%)patients who experienced major morbidity were salvaged after aggre-ssive treatment of their ***(3.5%)died from bleeding pseudoaneurysm(1),septic shock secondary to a bile leak(1),anastomotic leak(1),and myocardial infarction(1).There was a significantly greater salvage rate in patients with American Society of Anesthesiologists scores≤2(93.3%vs 25%;P=0.0024).CONCLUSION This paper adds to the growing body of evidence that volume alone should not be used as a marker of quality for patients requiring *** low volumes at our facility,we demonstrated that 87.9%of patients were rescued from major *** attributed this to several factors including development of rescue protocols,the competence of the pancreatic surgery teams and continuous,and adaptive learning by the entire institution,cul-minating in the development of tailored peri-pancreatectomy protoc

关键词： Pancreas Complication Rescue Failure Morbidity Mortality Pancreaticoduodenectomy

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Application of Deep Learning on Single-cell RNA Sequencing Data Analysis:A Review

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Genomics, Proteomics & Bioinformatics 2022年第5期20卷 814-835页

作者： Matthew Brendel Chang Su Zilong Bai Hao Zhang Olivier Elemento Fei Wang department of Population Health Sciences Weill Cornell MedicineCornell UniversityNew YorkNY 10065USA Institute for Computational Biomedicine Caryl and Israel Englander Institute for Precision MedicineDepartment of Physiology and BiophysicsWeill Cornell MedicineCornell UniversityNew YorkNY 10065USA department of Health Service Administration and Policy Temple UniversityPhiladelphiaPA 19122USA

Single-cell RNA sequencing(scRNA-seq)has become a routinely used technique to quantify the gene expression profile of thousands of single cells *** of scRNA-seq data plays an important role in the study of cell states and phenotypes,and has helped elucidate biological processes,such as those occurring during the development of complex organisms,and improved our understanding of disease states,such as cancer,diabetes,and coronavirus disease 2019(COVID-19).Deep learning,a recent advance of artificial intelligence that has been used to address many.problems involving large datasets,has also emerged as a promising tool for scRNA-seq data analysis,as it has a capacity to extract informative and compact features from noisy,heterogeneous,and high-dimensional scRNA-seq data to improve downstream *** present review aims at surveying recently developed deep learning techniques in scRNA-seq data analysis,identifying key steps within the scRNA-seq data analysis pipeline that have been advanced by deep learning,and explaining the benefits of deep learning over more conventional analytic ***,we summarize the challenges in current deep learning approaches faced within scRNA-seq data and discuss potential directions for improvements in deep learning algorithms for scRNA-seq data analysis.

关键词： Single-cell RNA sequencing Single-cell sequencing Deep learning Deep neural network Artificial intelligence

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The RNA helicase DHX15 is a critical regulator of natural killer-cell homeostasis and functions

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Cellular & Molecular Immunology 2022年第6期19卷 687-701页

作者： Guangchuan Wang Xiang Xiao Yixuan Wang Xiufeng Chu Yaling Dou Laurie J.Minze Rafik M.Ghobrial Zhiqiang Zhang Xian C.Li Immunobiology and Transplant Science Center and department of Surgery Houston Methodist HospitalTexas Medical CenterHoustonTXUSA department of Surgery Weill Cornell Medical College of Cornell UniversityNew YorkNYUSA

The RNA helicase DHX15 is widely expressed in immune cells and traditionally thought to be an RNA splicing factor or a viral RNA ***,the role of DHX15 in NK-cell activities has not been studied thus ***,we generated Dhx15-floxed mice and found that conditional deletion of Dhx15 in NK cells(Ncr1CreDhx15fl/fl mice)resulted in a marked reduction in NK cells in the periphery and that the remaining Dhx15-deleted NK cells failed to acquire a mature *** a result,Dhx15-deleted NK cells exhibited profound defects in their cytolytic *** also found that deletion of Dhx15 in NK cells abrogated their responsiveness to IL-15,which was associated with inhibition of IL-2/IL-15Rβ(CD122)expression and IL-15R *** defects in Dhx15-deleted NK cells were rescued by ectopic expression of a constitutively active form of ***,DHX15 did not affect CD122 mRNA splicing and stability in NK cells but instead facilitated the surface expression of CD122,likely through interaction with its 3′UTR,which was dependent on the ATPase domain of DHX15 rather than its splicing ***,our data identify a key role for DHX15 in regulating NK-cell activities and provide novel mechanistic insights into how DHX15 regulates the IL-15 signaling pathway in NK cells.

关键词： DEAH-box helicase 15(DHX15) Innate immunity Natural killer(NK)cells Homeostasis IL-15 signaling pathway

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RANKL-responsive epigenetic mechanism reprograms macrophages into bone-resorbing osteoclasts

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Cellular & Molecular Immunology 2023年第1期20卷 94-109页

作者： Seyeon Bae Kibyeong Kim Keunsoo Kang Haemin Kim Minjoon Lee Brian Oh Kaichi Kaneko Sungkook Ma Jae Hoon Choi Hojoong Kwak Eun Young Lee Sung Ho Park Kyung-Hyun Park-Min Arthritis and Tissue Degeneration Program David Z.Rosensweig Genomics Research CenterHospital for Special SurgeryNew YorkNY10021USA department of Medicine Weill Cornell Medical CollegeNew YorkNY10065USA department of Biological Science Ulsan National Institute of Science&Technology(UNIST)Ulsan44919Republic of Korea department of Life Science College of Natural SciencesResearch Institute for Natural SciencesHanyang UniversitySeoulKorea department of Microbiology Dankook UniversityCheonan3116Republic of Korea department of Molecular Biology and Genetics Cornell UniversityIthacaUSA Division of Rheumatology Department of Internal MedicineSeoul National University College of MedicineSeoulKorea BCMB Allied Program Weill Cornell Graduate School of Medical SciencesNew YorkNY10021USA

Monocyte/macrophage lineage cells are highly plastic and can differentiate into various cells under different environmental stimuli. Bone-resorbing osteoclasts are derived from the monocyte/macrophage lineage in response to receptor activator of NF-κB ligand (RANKL). However, the epigenetic signature contributing to the fate commitment of monocyte/macrophage lineage differentiation into human osteoclasts is largely unknown. In this study, we identified RANKL-responsive human osteoclast-specific superenhancers (SEs) and SE-associated enhancer RNAs (SE-eRNAs) by integrating data obtained from ChIP-seq, ATAC-seq, nuclear RNA-seq and PRO-seq analyses. RANKL induced the formation of 200 SEs, which are large clusters of enhancers, while suppressing 148 SEs in macrophages. RANKL-responsive SEs were strongly correlated with genes in the osteoclastogenic program and were selectively increased in human osteoclasts but marginally presented in osteoblasts, CD4+ T cells, and CD34+ cells. In addition to the major transcription factors identified in osteoclasts, we found that BATF binding motifs were highly enriched in RANKL-responsive SEs. The depletion of BATF1/3 inhibited RANKL-induced osteoclast differentiation. Furthermore, we found increased chromatin accessibility in SE regions, where RNA polymerase II was significantly recruited to induce the extragenic transcription of SE-eRNAs, in human osteoclasts. Knocking down SE-eRNAs in the vicinity of the NFATc1 gene diminished the expression of NFATc1, a major regulator of osteoclasts, and osteoclast differentiation. Inhibiting BET proteins suppressed the formation of some RANKL-responsive SEs and NFATc1-associated SEs, and the expression of SE-eRNA:NFATc1. Moreover, SE-eRNA:NFATc1 was highly expressed in the synovial macrophages of rheumatoid arthritis patients exhibiting high-osteoclastogenic potential. Our genome-wide analysis revealed RANKL-inducible SEs and SE-eRNAs as osteoclast-specific signatures, which may contribute to t

关键词： Osteoclasts super-enhancers enhancer RNAs Rheumatoid arthritis

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COVID-19 Stay-At-Home Orders and Older Adults’ Cognitive Health — United States, June 2018–February 2022

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China CDC weekly 2022年第45期4卷 1002-1006,I0003页

作者： Nam Sun Choi Tianzi Li Jingxiang Pan Selena Yue Jing Li department of Population Health Sciences Weill Cornell Medical CollegeCornell UniversityNew YorkNYU.S. The Comparative Health Outcomes Policy and Economics(CHOICE)InstituteSchool of PharmacyUniversity of WashingtonSeattleWAU.S.

What is already known about this topic?Lack of social activities is known to negatively impact cognitive functioning and increase risk of cognitive impairment,including dementia,among older *** is added by this report?Coronavirus disease 2019(COVID-19)stay-at-home orders implemented in the *** during the pandemic were not found to negatively affect cognitive functioning of older *** are the implications for public health practice?There may have been no severe,unintended consequences of the COVID-19 stay-at-home orders in terms of their impact on cognitive functioning and risk of dementia among older adults,lending further support to use of such orders.

关键词： impairment consequences COV

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Dual role of lipids for genome stability and pluripotency facilitates full potency of mouse embryonic stem cells

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蛋白质与细胞:英文版 2023年第8期14卷 591-602页

作者： Liangwen Zhong Miriam Gordillo Xingyi Wang Yiren Qin Yuany.an Huang Alexey Soshnev Ritu Kumar Gouri Nanjangud Daylon James C.David Allis Todd Evans Bryce Carey Duancheng Wen department of Reproductive Medicine Ronald O.Perelman and Claudia Cohen Center for Reproductive MedicineWeill Cornell MedicineNew YorkNY 10065USA department of Surgery Weill Cornell Medical College1300 York AvenueNew YorkNY 10065USA Laboratory of Chromatin Biology and Epigenetics The Rockefeller UniversityNew YorkNY 10065USA Cold Spring Harbor Laboratory Cold Spring HarborNY 11724USA Molecular Cytogenetics Core.Memorial Sloan Kettering Cancer Center New YorkNY 10065USA department of Neuroscience Developmental and Regenerative BiologyUniversity of Texas at San AntonioOne UTSA CircleSan AntonioTX 78249USA Gladstone Institutes 1650 Owens StSan FranciscoCA94158USA

While Mek1/2 and Gsk3βinhibition("2i")supports the maintenance of murine embryonic stem cells(EsCs)in a homogenous naive state,prolonged culture in 2i results in aneuploidy and DNA hypomethylation that impairs developmental ***,2i fails to support derivation and culture of fully potent female *** we find that mouse ESCs cultured in 2i/LIF supplemented with lipid-rich albumin(AlbuMAx)undergo pluripotency transition yet maintain genomic stability and full potency over long-term ***,lipids in AlbuMAx impact intracellular metabolism including nucleotide biosynthesis,lipid biogenesis,and TCA cycle intermediates,with enhanced expression of DNMT3s that prevent DNA *** induce a formative-like pluripotent state through direct stimulation of Erk2 phosphorylation,which also alleviates X chromosome loss in female ***,both male and female"all-ESc"mice can be generated from de novo derived ESCs using AlbuMAXbased *** findings underscore the importance of lipids to pluripotency and link nutrient cues to genome integrity in early development.

关键词： mouse pluripotent stem cells lipids pluripotency transition genomic stability developmental potency nucleotide pool depletion 2i medium X chromosome loss femaleall-EsC mice

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