tbuckley/cabot-search huggingface dataset:
Baseline viral load and on-treatment hepatocellular carcinoma risk in chronic hepatitis B: A multinational cohort study
Authors: Won-Mook Choi, Terry Cheuk-Fung Yip, Grace Lai-Hung Wong, W. Ray Kim, Leland J. Yee, Craig Brooks-Rooney, Tristan Curteis, Laura J. Clark, Zarena Jafry, Chien-Hung Chen, Chi-Yi Chen, Yi-Hsiang Huang, Young-Joo Jin, Dae Won Jun, Jin-Wook Kim, Neung Hwa Park, Cheng-Yuan Peng, Hyun Phil Shin, Jung Woo Shin, Yao-Hsu Yang, Young-Suk Lim
Journal: Clinical Gastroenterology and Hepatology (2024)

Background & AimsHepatocellular carcinoma (HCC) risk persists in patients with chronic hepatitis B (CHB) despite antiviral therapy. The relationship between pre-treatment baseline hepatitis B virus (HBV) viral load and HCC risk during antiviral treatment remains uncertain.MethodsThis multinational cohort study aimed to investigate the association between baseline HBV viral load and on-treatment HCC risk in 20,826 noncirrhotic, hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients with baseline HBV DNA levels ≥2000 IU/mL (3.30 log10 IU/mL) who initiated entecavir or tenofovir treatment. The primary outcome was on-treatment HCC incidence, stratified by baseline HBV viral load as a categorical variable.ResultsIn total, 663 patients developed HCC over a median follow-up of 4.1 years, with an incidence rate of 0.81 per 100 person-years (95% confidence interval [CI], 0.75–0.87). Baseline HBV viral load was significantly associated with HCC risk in a non-linear parabolic pattern, independent of other factors. Patients with baseline viral load between 6.00 and 7.00 log10 IU/mL had the highest on-treatment HCC risk (adjusted hazard ratio, 4.28; 95% CI, 2.15–8.52; P < .0001) compared with those with baseline viral load ≥8.00 log10 IU/mL, who exhibited the lowest HCC risk.ConclusionBaseline viral load showed a significant, non-linear, parabolic association with HCC risk during antiviral treatment in noncirrhotic patients with CHB. Early initiation of antiviral treatment based on HBV viral load may help prevent irreversible HCC risk accumulation in patients with CHB.Graphical abstract
Travel Time to Treating Center is Associated with Diagnostic Delay in Pediatric Inflammatory Bowel Disease
Authors: Joi F. McLaughlin, Tiffany Linville, Traci W. Jester, Tuvia A. Marciano, Farrah Lazare, Jennifer L. Dotson, Charles Samson, Barbara Niklinska-Schirtz, Jose Cabrera, Ian Leibowtiz, Suruchi Batra, Rana Ammoury, Jennifer A. Strople, Shehzad Saeed, Kelly C. Sandberg, Jeanne Tung, Sofia G. Verstraete, Ryan F. Cox, Sera Na, Steven J. Steiner, Sabina A. Ali, Esther J. Israel, Jill Dorsey, Jeremy Adler, Yuliya Rekhtman, Matthew D. Egberg, Emmala Ryan Waduge, Jen Savas, Colleen M. Brensinger, James D. Lewis, Michael D. Kappelman
Journal: Clinical Gastroenterology and Hepatology (2024)
Safety and efficacy of blinatumomab as bridge-to-transplant for B-cell acute lymphoblastic leukemia in first complete remission with no detectable minimal residual disease
Authors: Jialing Lu, Xiebing Bao, Jihao Zhou, Xiaoli Li, Zhewei He, Yujie Ji, Shengli Xue, Suning Chen, Depei Wu, Qi Hu, Peng Ke, Xiao Ma
Journal: Blood Cancer Journal (2024)

Safety and efficacy of blinatumomab as bridge-to-transplant for B-cell
Venetoclax with hypomethylating agents versus intensive chemotherapy in newly diagnosed acute myeloid leukemia with myelodysplasia related changes: A propensity score-matched analysis based on International Consensus Classification
Authors: Chao-Ling Wan, Yu-Qing Liu, Fang-Tong Liu, Yuan-Hong Huang, Han-Yu Cao, Si-Man Huang, Kai-Wen Tan, Shuai-Shuai Ge, Miao Wang, Mei-Jing Liu, Zi-Hao Wang, Zheng Li, Sheng-Li Xue, Hai-Ping Dai
Journal: Blood Cancer Journal (2024)
FAT1 is a target antigen in a subset of de novo allograft membranous nephropathy associated with antibody mediated rejection
Authors: Sanjeev Sethi, Benjamin Madden, Marta Casal Moura, Samih H Nasr, Mariam P Alexander, Hanna Debiec, Nate Torrel, LouAnn Gross, Vivian Negron, Ulrich Specks, Fernando C Fervenza, Mark Haas, Pierre Ronco, Ibrahim Batal
Journal: Kidney International (2024)
Differing sensitivities to angiotensin converting enzyme inhibition of kidney disease mediated by APOL1 high-risk variants G1 and G2
Authors: Esilida Sula Karreci, Sonako Jacas, Olivia Donovan, Diana Pintye, Nicholas Wiley, Zsuzsanna K. Zsengeller, Johannes Schlondorff, Seth L. Alper, David J. Friedman, Martin R. Pollak
Journal: Kidney International (2024)
Global Temporal Trends And Projections of Acute Hepatitis E Incidence Among Women of Childbearing Age: Age-Period-Cohort Analysis 2021
Authors: Deliang Huang, Huiyi Lai, Xia Shi, Jinyan Jiang, Zhibin Zhu, Jinghan Peng, Siyu Zhang, Yuanyuan Chen, Hong Yu, Qi Zhao, Yanping Chen, Jun Chen
Journal: Journal of Infection (2024)

Acute hepatitis E (AHE) poses a significant threat to global public health, particularly among women of childbearing age (WCBA), who are at heightened risk for severe pregnancy-related complications. This study aimed to delineate the temporal trends and project future incidence of AHE in WCBA, providing insights crucial for targeted prevention and control strategies.
Arginine-solubilized lipoic acid-induced β-sheets of silk fibroin-strengthened hydrogel for postoperative rehabilitation of breast cancer
Authors: Zhuodan Zhang, Yi Xia, Xinyi Li, Qian Zhang, Yuanhao Wu, Chunyan Cui, Jianfeng Liu, Wenguang Liu
Journal: Bioactive Materials (2024)

Breast cancer is the most common cancer among women worldwide, and adjuvant radiotherapy (RT) following tumor removal is one of the most commonly used treatments for breast cancer. However, the high risk of tumor recurrence and inevitable radiation skin injury after RT remain fatal problems, seriously challenging the patient's postoperative rehabilitation. Herein, a multifunctional poly (lipoic acid)-based hydrogel is constructed through one-step heating the mixture of α-lipoic acid (LA)/arginine (Arg)/silk fibroin (SF), without introducing any non-natural molecules. The multiple synergistic interactions among LA, Arg, and SF not only enhance the solubilization of LA in aqueous systems but also stabilize poly(lipoic acid) through strong salt bridge hydrogen bonds and ionic hydrogen bonds. Intriguingly, the LA-based surfactant induced β-sheet transformation of SF can further modulate the bulk strength of the hydrogel. Regulating the content of LA in hydrogels not only allows efficient control of hydrogel bioactivity but also enables the evolution of hydrogels from injectable forms to adhesive patches. Based on the different biological activities and forms of hydrogels, they can be implanted internally or applied externally on the mice's skin, achieving simultaneous prevention of tumor recurrence post-surgery and assistance in treating radiation-induced skin damage after radiotherapy.
Surgical face masks to prevent respiratory symptoms
Authors: Rachel L Amdur, Jeffrey A Linder
Journal: BMJ (2024)

Early in the covid-19 pandemic, face masks were promoted as an important non-pharmaceutical intervention. 1Masking makes intuitive sense.Most cultures teach children to "catch your cough" and "cover your mouth when you sneeze."In many Asian countries it was a prepandemic cultural norm for people to wear masks.However, many commentators have reasonably asked, "do masks work, and should they be recommended?"These seemingly simple questions have proved challenging to answer, and, in some places, policies on masking-especially mask mandates-are controversial and politicized. 2 The weight of randomized and observational evidence to date suggests that masks probably reduce the risk of covid-19 infection. 3 Now, in the linked paper, Solberg and colleagues (doi:10.1136/bmj
Social Genomic Determinants of Health: Understanding the Molecular Pathways by Which Neighborhood Disadvantage Affects Cancer Outcomes
Authors: Neha Goel, Alexandra Hernandez, Steven W. Cole
Journal: Journal of Clinical Oncology (2024)

PURPOSE Neighborhoods represent complex environments with unique social, cultural, physical, and economic attributes that have major impacts on disparities in health, disease, and survival. Neighborhood disadvantage is associated with shorter breast cancer recurrence-free survival (RFS) independent of individual-level (race, ethnicity, socioeconomic status, insurance, tumor characteristics) and health system-level determinants of health (receipt of guideline-concordant treatment). This persistent disparity in RFS suggests unaccounted mechanisms such as more aggressive tumor biology among women living in disadvantaged neighborhoods compared with advantaged neighborhoods. The objective of this article was to provide a clear framework and biological mechanistic explanation for how neighborhood disadvantage affects cancer survival. METHODS Development of a translational epidemiological framework that takes a translational disparities approach to study cancer outcome disparities through the lens of social genomics and social epigenomics. RESULTS The social genomic determinants of health, defined as the physiological gene regulatory pathways (ie, neural/endocrine control of gene expression and epigenetic processes) through which contextual factors, particularly one's neighborhood, can affect activity of the cancer genome and the surrounding tumor microenvironment to alter disease progression and treatment outcomes. CONCLUSION We propose a novel, multilevel determinants of health model that takes a translational epidemiological approach to evaluate the interplay between political, health system, social, psychosocial, individual, and social genomic determinants of health to understand social disparities in oncologic outcomes. In doing so, we provide a concrete biological pathway through which the effects of social processes and social epidemiology come to affect the basic biology of cancer and ultimately clinical outcomes and survival.
Menin inhibitors in pediatric acute leukemia: a comprehensive review and recommendations to accelerate progress in collaboration with adult leukemia and the international community
Authors: Branko Cuglievan, Hagop Kantarjian, Jeffrey E. Rubnitz, Todd M. Cooper, C. Michel Zwaan, Jessica A. Pollard, Courtney D. DiNardo, Tapan M. Kadia, Erin Guest, Nicholas J. Short, David McCall, Naval Daver, Cesar Nunez, Fadi G. Haddad, Miriam Garcia, Kapil N. Bhalla, Abhishek Maiti, Samanta Catueno, Warren Fiskus, Bing Z. Carter, Amber Gibson, Michael Roth, Sajad Khazal, Priti Tewari, Hussein A. Abbas, Wallace Bourgeois, Michael Andreeff, Neerav N. Shukla, Danh D. Truong, Jeremy Connors, Joseph A. Ludwig, Janine Stutterheim, Elisabeth Salzer, Kristian L. Juul-Dam, Koji Sasaki, Kris M. Mahadeo, Sarah K. Tasian, Gautam Borthakur, Samantha Dickson, Nitin Jain, Elias Jabbour, Soheil Meshinchi, Guillermo Garcia-Manero, Farhad Ravandi, Eytan M. Stein, E. Anders Kolb, Ghayas C. Issa
Journal: Leukemia (2024)

Abstract Aberrant expression of HOX and MEIS1 family genes, as seen in KMT2A-rearranged, NUP98-rearranged, or NPM1-mutated leukemias leads to arrested differentiation and leukemia development. HOX family genes are essential gatekeepers of physiologic hematopoiesis, and their expression is regulated by the interaction between KMT2A and menin. Menin inhibitors block this interaction, downregulate the abnormal expression of MEIS1 and other transcription factors and thereby release the differentiation block. Menin inhibitors show significant clinical efficacy against KMT2A-rearranged and NPM1-mutated acute leukemias, with promising potential to address unmet needs in various pediatric leukemia subtypes. In this collaborative initiative, pediatric and adult hematologists/oncologists, and stem cell transplant physicians have united their expertise to explore the potential of menin inhibitors in pediatric leukemia treatment internationally. Our efforts aim to provide a comprehensive clinical overview of menin inhibitors, integrating preclinical evidence and insights from ongoing global clinical trials. Additionally, we propose future international, inclusive, and efficient clinical trial designs, integrating pediatric populations in adult trials, to ensure broad access to this promising therapy for all children and adolescents with menin-dependent leukemias.
COVID-19 and multiple sclerosis: challenges and lessons for patient care
Authors: Luca Prosperini, Georgina Arrambide, Elisabeth G Celius, Delia Goletti, Joep Killestein, Daphne Kos, Luigi Lavorgna, Celine Louapre, Maria Pia Sormani, Dominika Stastna, Tjalf Ziemssen, Massimiliano Di Filippo
Journal: The Lancet Regional Health - Europe (2024)

During the COVID-19 pandemic, people with multiple sclerosis (MS) and their healthcare providers have faced unique challenges related to the interaction between SARS-CoV-2, underlying neurological disease and the use of disease-modifying treatments (DMTs). Key concerns arose, primarily related to the possibility that SARS-CoV-2 infection could trigger the initial demyelinating event or exacerbate disease activity. Another major concern was the safety and efficacy of the COVID-19 vaccines, especially for patients undergoing specific treatments that could weaken their antibody responses. In the post-infection phase, identifying long COVID in patients with MS has been complicated due to the large overlap between post-infection sequelae and MS symptoms. In addition, disruptions in health and rehabilitation services have made it difficult for MS patients to access care. This Series article explores current evidence on the interaction between MS and SARS-CoV-2, identifies the challenges posed by the COVID-19 pandemic in the care of patients with MS, and discusses the significant adoption of digital health solutions, including telemedicine and new technology-based rehabilitation approaches. Based on lessons learned, recommendations and future directions are offered for managing patients with MS, rethinking healthcare systems and improving health outcomes in the post-COVID-19 pandemic era.
The Cortisol Awakening Response: Regulation and Functional Significance
Authors: Tobias Stalder, Henrik Oster, James L Abelson, Katharina Huthsteiner, Tim Klucken, Angela Clow
Journal: Endocrine Reviews (2024)

In healthy individuals, the majority of cortisol secretion occurs within several hours surrounding morning awakening. A highly studied component of this secretory period is the cortisol awakening response (CAR), the rapid increase in cortisol levels across the first 30-45 min after morning awakening. This strong cortisol burst at the start of the active phase has been proposed to be functional in preparing the organism for the challenges of the upcoming day. Here, we review evidence on key regulatory and functional processes of the CAR and develop an integrative model of its functional role. Specifically, we propose that, in healthy individuals, the CAR is closely regulated by an intricate dual-control system, which draws upon key circadian, environmental and neurocognitive processes to best predict the daily need for cortisol-related action. Fine-tuned CAR expression, in turn, is then assumed to induce potent glucocorticoid action via rapid non-genomic and slower genomic pathways (e.g., affecting circadian clock gene expression) to support and modulate daily activity through relevant metabolic, immunological and neurocognitive systems. We propose that this concerted action is adaptive in mediating two main functions: a primary process to mobilize resources to meet activity-related demands and a secondary process to help the organism counterregulate adverse prior-day emotional experiences.
Salmonella re-engineers the intestinal environment to break colonization resistance in the presence of a compositionally intact microbiota
Authors: Andrew W L Rogers, Lauren C Radlinski, Henry Nguyen, Connor R Tiffany, Thaynara Parente Carvalho, Hugo L P Masson, Michael L Goodson, Lalita Bechtold, Kohei Yamazaki, Megan J Liou, Brittany M Miller, Scott P Mahan, Briana M Young, Aurore M Demars, Sophie R Gretler, Anaïs B Larabi, Jee-Yon Lee, Derek J Bays, Renee M Tsolis, Andreas J Bäumler
Journal: Cell Host & Microbe (2024)

The gut microbiota prevents harmful microbes from entering the body, a function known as colonization resistance. The enteric pathogen Salmonella enterica serovar (S.) Typhimurium uses its virulence factors to break colonization resistance through unknown mechanisms. Using metabolite profiling and genetic analysis, we show that the initial rise in luminal pathogen abundance was powered by a combination of aerobic respiration and mixed acid fermentation of simple sugars, such as glucose, which resulted in their depletion from the metabolome. The initial rise in the abundance of the pathogen in the feces coincided with a reduction in the cecal concentrations of acetate and butyrate and an increase in epithelial oxygenation. Notably, these changes in the host environment preceded changes in the microbiota composition. We conclude that changes in the host environment can weaken colonization resistance even in the absence of overt compositional changes in the gut microbiota.
Current and future role of MRI in the diagnosis and prognosis of multiple sclerosis
Authors: Maria A Rocca, Paolo Preziosa, Frederik Barkhof, Wallace Brownlee, Massimiliano Calabrese, Nicola De Stefano, Cristina Granziera, Stefan Ropele, Ahmed T Toosy, Àngela Vidal-Jordana, Massimiliano Di Filippo, Massimo Filippi
Journal: The Lancet Regional Health - Europe (2024)

In the majority of cases, multiple sclerosis (MS) is characterized by reversible episodes of neurological dysfunction, often followed by irreversible clinical disability. Accurate diagnostic criteria and prognostic markers are critical to enable early diagnosis and correctly identify patients with MS at increased risk of disease progression. The 2017 McDonald diagnostic criteria, which include magnetic resonance imaging (MRI) as a fundamental paraclinical tool, show high sensitivity and accuracy for the diagnosis of MS allowing early diagnosis and treatment. However, their inappropriate application, especially in the context of atypical clinical presentations, may increase the risk of misdiagnosis. To further improve the diagnostic process, novel imaging markers are emerging, but rigorous validation and standardization is still needed before they can be incorporated into clinical practice. This Series article discusses the current role of MRI in the diagnosis and prognosis of MS, while examining promising MRI markers, which could serve as reliable predictors of subsequent disease progression, helping to optimize the management of individual patients with MS. We also explore the potential of new technologies, such as artificial intelligence and automated quantification tools, to support clinicians in the management of patients. Yet, to ensure consistency and improvement in the use of MRI in MS diagnosis and patient follow-up, it is essential that standardized brain and spinal cord MRI protocols are applied, and that interpretation of results is performed by qualified (neuro)radiologists in all countries.
Identification and evolution of predictors of Sjögren's disease-associated mucosa-associated lymphoid tissue lymphoma development over time: a case-control study
Authors: Andreas V Goules, Loukas Chatzis, Vasilis C Pezoulas, Markos Patsouras, Clio Mavragani, Luca Quartuccio, Chiara Baldini, Salvatore De Vita, Dimitrios I Fotiadis, Athanasios G Tzioufas
Journal: The Lancet Rheumatology (2024)
Data-driven subclassification of ANCA-associated vasculitis: model-based clustering of a federated international cohort
Authors: Karl Gisslander, Arthur White, Louis Aslett, Zdenka Hrušková, Peter Lamprecht, Jacek Musiał, Jamsheela Nazeer, James Ng, Declan O'Sullivan, Xavier Puéchal, Matthew Rutherford, Mårten Segelmark, Benjamin Terrier, Vladimir Tesař, Michelangelo Tesi, Augusto Vaglio, Krzysztof Wójcik, Mark A Little, Aladdin J Mohammad
Journal: The Lancet Rheumatology (2024)
Disruption of nuclear speckle integrity dysregulates RNA splicing in C9ORF72-FTD/ALS
Authors: Rong Wu, Yingzhi Ye, Daoyuan Dong, Zhe Zhang, Shaopeng Wang, Yini Li, Noelle Wright, Javier Redding-Ochoa, Koping Chang, Shaohai Xu, Xueting Tu, Chengzhang Zhu, Lyle W Ostrow, Xavier Roca, Juan C Troncoso, Bin Wu, Shuying Sun
Journal: Neuron (2024)
Fluid biomarkers in multiple sclerosis: from current to future applications
Authors: Massimiliano Di Filippo, Lorenzo Gaetani, Diego Centonze, Harald Hegen, Jens Kuhle, Charlotte E Teunissen, Mar Tintoré, Luisa M Villar, Eline A J Willemse, Henrik Zetterberg, Lucilla Parnetti
Journal: The Lancet Regional Health - Europe (2024)

Multiple sclerosis (MS) is an immune-mediated inflammatory and degenerative disorder of the central nervous system (CNS) with heterogeneous clinical manifestations. In the last decade, the landscape of cerebrospinal fluid (CSF) and blood biomarkers as potential key tools for MS diagnosis, prognosis and treatment monitoring has evolved considerably, alongside magnetic resonance imaging (MRI). CSF analysis has the potential not only to provide information on the underlying immunopathology of the disease and exclude differential diagnoses, but also to predict the risk of future relapses and disability accrual, guide therapeutic decisions and thus improve patient outcomes. This Series article overviews the biological framework and current applicability of fluid biomarkers for MS, exploring their potential role in the molecular characterisation of the disease. We discuss recent advances in the field of neurochemistry that enabled the detection of brain-derived proteins in blood, opening the door to much more efficient longitudinal disease monitoring. Furthermore, we identify the current challenges in the application of fluid biomarkers for MS in a real-world setting, while offering recommendations for harnessing their full potential as key paraclinical tools to improve patient management and personalise treatment.
Less Deformable Erythrocyte Subpopulations Biomechanically Induce Endothelial Inflammation in Sickle Cell Disease
Authors: Christina Caruso, Xiaopo Cheng, Marina E Michaud, Hannah M Szafraniec, Beena E Thomas, Meredith Fay, Robert G Mannino, Xiao Zhang, Yumiko Sakurai, Wei Li, David Richard Myers, Clinton H. Joiner, David K Wood, Manoj Bhasin, Michael D Graham, Wilbur A Lam
Journal: Blood (2024)

Sickle cell disease (SCD) is canonically characterized by reduced red blood cell (RBC) deformability, leading to microvascular obstruction and inflammation. Although the biophysical properties of sickle RBCs are known to influence SCD vasculopathy, the contribution of poor RBC deformability to endothelial dysfunction has yet to be fully explored. Leveraging interrelated in vitro and in silico approaches, we introduce a new paradigm of SCD vasculopathy in which poorly deformable sickle RBCs directly cause endothelial dysfunction via mechanotransduction, during which endothelial cells sense and pathophysiologically respond to aberrant physical forces independently of microvascular obstruction, adhesion, or hemolysis. We demonstrate that perfusion of sickle RBCs or pharmacologically-dehydrated healthy RBCs into small venule-sized "endothelialized" microfluidics leads to pathologic physical interactions with endothelial cells that directly induce inflammatory pathways. Using a combination of computational simulations and large venule-sized endothelialized microfluidics, we observed that perfusion of heterogeneous sickle RBC subpopulations with varying deformability, as well as suspensions of dehydrated normal RBCs admixed with normal RBCs, leads to aberrant margination of the less-deformable RBC subpopulations toward the vessel walls, causing localized, increased shear stress. Increased wall stress is dependent on the degree of subpopulation heterogeneity and oxygen tension and leads to inflammatory endothelial gene expression via mechanotransductive pathways. Our multifaceted approach demonstrates that the presence of sickle RBCs with reduced deformability leads directly to pathological physical (ie, direct collisions and/or compressive forces) and shear-mediated interactions with endothelial cells and induces an inflammatory response, thereby elucidating the ubiquity of vascular dysfunction in SCD.