tbuckley/cabot-search huggingface dataset:
A new simplified risk assessment model enhances postoperative prophylaxis of venous thromboembolism in Chinese adult patients with inguinal hernia (CHAT-3): A prospective, multicenter, randomized controlled trial
Authors: Zhi-Chun Gu, Meng-Fei Dai, Meng Hu, Yi-Dan Yan, Hou-Wen Lin, Li Zhang, Zi-Chao Zhang, Chang Liu, Ning Ning, Hui Zhang, Nan Zhang, Yan Che, Jian-Wen Li, Ming-Gang Wang, Yu-Chen Liu
Journal: International Journal of Surgery (2024)

Background: Venous thromboembolism (VTE) significantly affects the prognosis of surgical patients with inguinal hernia. The complex Caprini score, commonly used for postoperative VTE risk assessment, poses practical challenges for surgeons in clinical settings. Methods: The CHAT-3 trial, a prospective, multicenter, randomized controlled trial, compared a simple three-factor model to assess VTE risk against routine practices in postinguinal hernia surgery (IHS) patients. The patients were randomly assigned (1:1) to the intervention or control arm. The intervention group used the three-factor model to identify patients at moderate or high risk of VTE for subsequent prophylaxis according to clinical guidelines. Both groups were followed for 4 weeks, with randomization implemented using computer-generated sequences. The primary outcome measured was the rate of VTE prophylaxis. Secondary outcomes included time spent on VTE risk assessment (surgeon self-reported), postoperative D-dimer trends, perioperative VTE occurrence, bleeding events, and the net clinical benefit. Results: Of the 1109 participants, 508 in the experimental group and 601 in the control group completed follow-up. The three-factor model showed higher VTE prophylaxis rates in all patients (pharmacologic prophylaxis: 26.2 vs. 6.00%, P &lt;0.001) and particularly in those at high risk (pharmacologic prophylaxis: 57.3 vs. 9.50%, P &lt;0.001). The experimental group significantly reduced VTE risk assessment time compared to the Caprini score (1.39±0.55 min vs. 5.73±1.35 min, P &lt;0.001). The experimental group had lower D-dimer levels (0.26±0.73 mg/l vs. 0.35±0.55 mg/l, P =0.028). In the experimental group, the patients did not experience an increased risk of VTE (0 vs. 1.66%, P =0.268) and bleeding (1.18 vs. 0.67%, P =0.558) compared to the controls. There was no significant difference in net clinical benefit, which combined VTE and bleeding events, between the experimental and control groups (1.18 vs. 0.83%, P =0.559). Conclusion: Applying the simple three-factor model in perioperative VTE management could quickly identify the patient with a high risk of VTE and improve the prophylaxis rate of perioperative VTE.
Optimizing clinico-genomic disease prediction across ancestries: a machine learning strategy with Pareto improvement
Authors: Yan Gao, Yan Cui
Journal: Genome Medicine (2024)

Accurate prediction of an individual's predisposition to diseases is vital for preventive medicine and early intervention. Various statistical and machine learning models have been developed for disease prediction using clinico-genomic data. However, the accuracy of clinico-genomic prediction of diseases may vary significantly across ancestry groups due to their unequal representation in clinical genomic datasets. We introduced a deep transfer learning approach to improve the performance of clinico-genomic prediction models for data-disadvantaged ancestry groups. We conducted machine learning experiments on multi-ancestral genomic datasets of lung cancer, prostate cancer, and Alzheimer's disease, as well as on synthetic datasets with built-in data inequality and distribution shifts across ancestry groups. Deep transfer learning significantly improved disease prediction accuracy for data-disadvantaged populations in our multi-ancestral machine learning experiments. In contrast, transfer learning based on linear frameworks did not achieve comparable improvements for these data-disadvantaged populations. This study shows that deep transfer learning can enhance fairness in multi-ancestral machine learning by improving prediction accuracy for data-disadvantaged populations without compromising prediction accuracy for other populations, thus providing a Pareto improvement towards equitable clinico-genomic prediction of diseases.
Pulmonary hypertension across the spectrum of left heart and lung disease
Authors: Barry A. Borlaug, Brett Larive, Robert P. Frantz, Paul Hassoun, Anna Hemnes, Evelyn Horn, Jane Leopold, Franz Rischard, Erika Berman‐Rosenzweig, Gerald Beck, Serpil Erzurum, Samar Farha, J. Emanuel Finet, Kristin B. Highland, Miriam Jacob, Christine Jellis, Reena Mehra, Rahul Renapurkar, Harsimran Singh, W.H. Wilson Tang, Rebecca Vanderpool, Jennifer Wilcox, Shilin Yu, Nicholas Hill
Journal: European Journal of Heart Failure (2024)
Diacylglycerol kinase delta overexpression improves glucose clearance and protects against the development of obesity
Authors: Maxence Jollet, Flavia Tramontana, Lake Q. Jiang, Melissa L. Borg, Mladen Savikj, Michael S. Kuefner, Julie Massart, Thais de Castro Barbosa, Louise Mannerås-Holm, Antonio Checa, Nicolas J. Pillon, Alexander V. Chibalin, Marie Björnholm, Juleen R. Zierath
Journal: Metabolism (2024)

Diacylglycerol kinase (DGK) isoforms catalyze an enzymatic reaction that removes diacylglycerol (DAG) and thereby terminates protein kinase C signaling by converting DAG to phosphatidic acid. DGKδ (type II isozyme) downregulation causes insulin resistance, metabolic inflexibility, and obesity. Here we determined whether DGKδ overexpression prevents these metabolic impairments.
PGC-1α-mediated imbalance of mitochondria-lipid droplet homeostasis in neomycin-induced ototoxicity and nephrotoxicity
Authors: Bin Chen, Cheng Cheng, Yunhao Wu, Siyu Li, Mo Han, Le Zhen, Ying Peng, Suhan Guo, Kaidi Shen, Xia Gao, Renjie Chai, Guangji Wang, Fang Zhou
Journal: Acta Pharmaceutica Sinica B (2024)

Ototoxicity and nephrotoxicity are the most prevalent side effects of aminoglycoside antibiotics (gentamicin, amikacin, neomycin) and platinum anti-tumor drugs (cisplatin, carboplatin). The inner ear and kidney share similarities in drug deposition and toxicity, but the underlying pathophysiological mechanisms remain unclear. Investigating the shared mechanisms and metabolic alterations in these distinct organs will provide valuable insights for clinical therapy. A strong correlation has been identified between the spatiotemporal accumulation patterns of neomycin and the specific occurrence of lipid metabolism disorders in these two organs. The primary allocation of neomycin to mitochondria results in a notable escalation in the accumulation of lipid droplets (LDs) and more interactions between mitochondria and LDs, leading to a sequence of disturbances in lipid metabolism, such as increased lipid ROS and the blocked transfer of fatty acids from LDs to mitochondria. PGC-1
Lansoprazole (LPZ) reverses multidrug resistance (MDR) in cancer through impeding ATP-binding cassette (ABC) transporter-mediated chemotherapeutic drug efflux and lysosomal sequestration.
Authors: Ning Ji, Hui Li, Yixuan Zhang, Yuelin Li, Peiyu Wang, Xin Chen, Yi-Nan Liu, Jing-Quan Wang, Yuqi Yang, Zhe-Sheng Chen, Yueguo Li, Ran Wang, Dexin Kong
Journal: Drug Resistance Updates (2024)
Gastroenteropancreatic neuroendocrine neoplasms: current development, challenges, and clinical perspectives
Authors: Xian-Bin Zhang, Yi-Bao Fan, Rui Jing, Mikiyas Amare Getu, Wan-Ying Chen, Wei Zhang, Hong-Xia Dong, Tikam Chand Dakal, Akhtar Hayat, Hua-Jun Cai, Milad Ashrafizadeh, A. M. Abd El-Aty, Ahmet Hacimuftuoglu, Peng Liu, Tian-Feng Li, Gautam Sethi, Kwang Seok Ahn, Yavuz Nuri Ertas, Min-Jiang Chen, Jian-Song Ji, Li Ma, Peng Gong
Journal: Military Medical Research (2024)

Abstract Neuroendocrine neoplasms (NENs) are highly heterogeneous and potentially malignant tumors arising from secretory cells of the neuroendocrine system. Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are the most common subtype of NENs. Historically, GEP-NENs have been regarded as infrequent and slow-growing malignancies; however, recent data have demonstrated that the worldwide prevalence and incidence of GEP-NENs have increased exponentially over the last three decades. In addition, an increasing number of studies have proven that GEP-NENs result in a limited life expectancy. These findings suggested that the natural biology of GEP-NENs is more aggressive than commonly assumed. Therefore, there is an urgent need for advanced researches focusing on the diagnosis and management of patients with GEP-NENs. In this review, we have summarized the limitations and recent advancements in our comprehension of the epidemiology, clinical presentations, pathology, molecular biology, diagnosis, and treatment of GEP-NETs to identify factors contributing to delays in diagnosis and timely treatment of these patients.
Cell shape sensing licenses dendritic cells for homeostatic migration to lymph nodes
Authors: Zahraa Alraies, Claudia A. Rivera, Maria-Graciela Delgado, Doriane Sanséau, Mathieu Maurin, Roberto Amadio, Giulia Maria Piperno, Garett Dunsmore, Aline Yatim, Livia Lacerda Mariano, Anna Kniazeva, Vincent Calmettes, Pablo J. Sáez, Alice Williart, Henri Popard, Matthieu Gratia, Olivier Lamiable, Aurélie Moreau, Zoé Fusilier, Lou Crestey, Benoit Albaud, Patricia Legoix, Anne S. Dejean, Anne-Louise Le Dorze, Hideki Nakano, Donald N. Cook, Toby Lawrence, Nicolas Manel, Federica Benvenuti, Florent Ginhoux, Hélène D. Moreau, Guilherme P. F. Nader, Matthieu Piel, Ana-Maria Lennon-Duménil
Journal: Nature Immunology (2024)

Immune cells experience large cell shape changes during environmental patrolling because of the physical constraints that they encounter while migrating through tissues. These cells can adapt to such deformation events using dedicated shape-sensing pathways. However, how shape sensing affects immune cell function is mostly unknown. Here, we identify a shape-sensing mechanism that increases the expression of the chemokine receptor CCR7 and guides dendritic cell migration from peripheral tissues to lymph nodes at steady state. This mechanism relies on the lipid metabolism enzyme cPLA
Gene × environment effects and mediation involving adverse childhood events, mood and anxiety disorders, and substance dependence
Authors: Henry R. Kranzler, Christal N. Davis, Richard Feinn, Zeal Jinwala, Yousef Khan, Ariadni Oikonomou, Damaris Silva-Lopez, Isabel Burton, Morgan Dixon, Jackson Milone, Sarah Ramirez, Naomi Shifman, Daniel Levey, Joel Gelernter, Emily E. Hartwell, Rachel L. Kember
Journal: Nature Human Behaviour (2024)
Identification of a longevity gene through evolutionary rate covariation of insect mito-nuclear genomes
Authors: Mei Tao, Jiani Chen, Chunlai Cui, Yandong Xu, Jingxiu Xu, Zheyi Shi, Jiaqi Yun, Junwei Zhang, Guo-Zheng Ou, Chao Liu, Yun Chen, Zeng-Rong Zhu, Ronghui Pan, Suhong Xu, Xue-xin Chen, Antonis Rokas, Yang Zhao, Sibao Wang, Jianhua Huang, Xing-Xing Shen
Journal: Nature Aging (2024)
CDC Clinical Guidelines on the Use of Doxycycline Postexposure Prophylaxis for Bacterial Sexually Transmitted Infection Prevention, United States, 2024
Authors: Laura H. Bachmann, Lindley A. Barbee, Philip Chan, Hilary Reno, Kimberly A. Workowski, Karen Hoover, Jonathan Mermin, Leandro Mena
Journal: MMWR Recommendations and Reports (2024)

No vaccines and few chemoprophylaxis options exist for the prevention of bacterial sexually transmitted infections (STIs) (specifically syphilis, chlamydia, and gonorrhea). These infections have increased in the United States and disproportionately affect gay, bisexual, and other men who have sex with men (MSM) and transgender women (TGW). In three large randomized controlled trials, 200 mg of doxycycline taken within 72 hours after sex has been shown to reduce syphilis and chlamydia infections by >70% and gonococcal infections by approximately 50%. This report outlines CDC's recommendation for the use of doxycycline postexposure prophylaxis (doxy PEP), a novel, ongoing, patient-managed biomedical STI prevention strategy for a selected population. CDC recommends that MSM and TGW who have had a bacterial STI (specifically syphilis, chlamydia, or gonorrhea) diagnosed in the past 12 months should receive counseling that doxy PEP can be used as postexposure prophylaxis to prevent these infections. Following shared decision-making with their provider, CDC recommends that providers offer persons in this group a prescription for doxy PEP to be self-administered within 72 hours after having oral, vaginal, or anal sex. The recommended dose of doxy PEP is 200 mg and should not exceed a maximum dose of 200 mg every 24 hours.Doxy PEP, when offered, should be implemented in the context of a comprehensive sexual health approach, including risk reduction counseling, STI screening and treatment, recommended vaccination and linkage to HIV PrEP, HIV care, or other services as appropriate. Persons who are prescribed doxy PEP should undergo bacterial STI testing at anatomic sites of exposure at baseline and every 3-6 months thereafter. Ongoing need for doxy PEP should be assessed every 3-6 months as well. HIV screening should be performed for HIV-negative MSM and TGW according to current recommendations.
Proteomic analysis of cardiorespiratory fitness for prediction of mortality and multisystem disease risks
Authors: Andrew S. Perry, Eric Farber-Eger, Tomas Gonzales, Toshiko Tanaka, Jeremy M. Robbins, Venkatesh L. Murthy, Lindsey K. Stolze, Shilin Zhao, Shi Huang, Laura A. Colangelo, Shuliang Deng, Lifang Hou, Donald M. Lloyd-Jones, Keenan A. Walker, Luigi Ferrucci, Eleanor L. Watts, Jacob L. Barber, Prashant Rao, Michael Y. Mi, Kelley Pettee Gabriel, Bjoern Hornikel, Stephen Sidney, Nicholas Houstis, Gregory D. Lewis, Gabrielle Y. Liu, Bharat Thyagarajan, Sadiya S. Khan, Bina Choi, George Washko, Ravi Kalhan, Nick Wareham, Claude Bouchard, Mark A. Sarzynski, Robert E. Gerszten, Soren Brage, Quinn S. Wells, Matthew Nayor, Ravi V. Shah
Journal: Nature Medicine (2024)

Abstract Despite the wide effects of cardiorespiratory fitness (CRF) on metabolic, cardiovascular, pulmonary and neurological health, challenges in the feasibility and reproducibility of CRF measurements have impeded its use for clinical decision-making. Here we link proteomic profiles to CRF in 14,145 individuals across four international cohorts with diverse CRF ascertainment methods to establish, validate and characterize a proteomic CRF score. In a cohort of around 22,000 individuals in the UK Biobank, a proteomic CRF score was associated with a reduced risk of all-cause mortality (unadjusted hazard ratio 0.50 (95% confidence interval 0.48–0.52) per 1 s.d. increase). The proteomic CRF score was also associated with multisystem disease risk and provided risk reclassification and discrimination beyond clinical risk factors, as well as modulating high polygenic risk of certain diseases. Finally, we observed dynamicity of the proteomic CRF score in individuals who undertook a 20-week exercise training program and an association of the score with the degree of the effect of training on CRF, suggesting potential use of the score for personalization of exercise recommendations. These results indicate that population-based proteomics provides biologically relevant molecular readouts of CRF that are additive to genetic risk, potentially modifiable and clinically translatable.
Cervical cancer screening using DNA methylation triage in a real-world population
Authors: Lena Schreiberhuber, James E. Barrett, Jiangrong Wang, Elisa Redl, Chiara Herzog, Charlotte D. Vavourakis, Karin Sundström, Joakim Dillner, Martin Widschwendter
Journal: Nature Medicine (2024)

Cervical cancer (CC) screening in women comprises human papillomavirus (HPV) testing followed by cytology triage of positive cases. Drawbacks, including cytology's low reproducibility and requirement for short screening intervals, raise the need for alternative triage methods. Here we used an innovative triage technique, the WID-qCIN test, to assess the DNA methylation of human genes DPP6, RALYL and GSX1 in a real-life cohort of 28,017 women aged ≥30 years who attended CC screening in Stockholm between January and March 2017. In the analysis of all 2,377 HPV-positive samples, a combination of WID-qCIN (with a predefined threshold) and HPV16 and/or HPV18 (HPV16/18) detected 93.4% of cervical intraepithelial neoplasia grade 3 and 100% of invasive CCs. The WID-qCIN/HPV16/18 combination predicted 69.4% of incident cervical intraepithelial neoplasia grade 2 or worse compared with 18.2% predicted by cytology. Cytology or WID-qCIN/HPV16/18 triage would require 4.1 and 2.4 colposcopy referrals to detect one cervical intraepithelial neoplasia grade 2 or worse, respectively, during the 6 year period. These findings support the use of WID-qCIN/HPV16/18 as an improved triage strategy for HPV-positive women.
Non-literacy biased, culturally fair cognitive detection tool in primary care patients with cognitive concerns: a randomized controlled trial
Authors: Joe Verghese, Rachel Chalmer, Marnina Stimmel, Erica Weiss, Jessica Zwerling, Rubina Malik, David Rasekh, Asif Ansari, Roderick A. Corriveau, Amy R. Ehrlich, Cuiling Wang, Emmeline Ayers
Journal: Nature Medicine (2024)

Dementia is often undiagnosed in primary care, and even when diagnosed, untreated. The 5-Cog paradigm, a brief, culturally adept, cognitive detection tool paired with a clinical decision support may reduce barriers to improving dementia diagnosis and care. We performed a randomized controlled trial in primary care patients experiencing health disparities (racial/ethnic minorities and socioeconomically disadvantaged). Older adults with cognitive concerns were assigned in a 1:1 ratio to the 5-Cog paradigm or control. Primary outcome was improved dementia care actions defined as any of the following endpoints within 90 days: new mild cognitive impairment syndrome or dementia diagnoses as well as investigations, medications or specialist referrals ordered for cognitive indications. Groups were compared using intention-to-treat principles with multivariable logistic regression. Overall, 1,201 patients (mean age 72.8 years, 72% women and 94% Black, Hispanic or Latino) were enrolled and 599 were assigned to 5-Cog and 602 to the control. The 5-Cog paradigm demonstrated threefold odds of improvement in dementia care actions over control (odds ratio 3.43, 95% confidence interval 2.32-5.07). No serious intervention-related adverse events were reported. The 5-Cog paradigm improved diagnosis and management in patients with cognitive concerns and provides evidence to promote practice change to improve dementia care actions in primary care.ClinicalTrials.gov: NCT03816644 .
Epigenetic and proteomic signatures associate with clonal hematopoiesis expansion rate
Authors: Taralynn M. Mack, Michael A. Raddatz, Yash Pershad, Daniel C. Nachun, Kent D. Taylor, Xiuqing Guo, Alan R. Shuldiner, Jeffrey R. O’Connell, Eimear E. Kenny, Ruth J. F. Loos, Susan Redline, Brian E. Cade, Bruce M. Psaty, Joshua C. Bis, Jennifer A. Brody, Edwin K. Silverman, Jeong H. Yun, Michael H. Cho, Dawn L. DeMeo, Daniel Levy, Andrew D. Johnson, Rasika A. Mathias, Lisa R. Yanek, Susan R. Heckbert, Nicholas L. Smith, Kerri L. Wiggins, Laura M. Raffield, April P. Carson, Jerome I. Rotter, Stephen S. Rich, Ani W. Manichaikul, C. Charles Gu, Yii-Der Ida Chen, Wen-Jane Lee, M. Benjamin Shoemaker, Dan M. Roden, Charles Kooperberg, Paul L. Auer, Pinkal Desai, Thomas W. Blackwell, Albert V. Smith, Alexander P. Reiner, Siddhartha Jaiswal, Joshua S. Weinstock, Alexander G. Bick
Journal: Nature Aging (2024)
Intravesical local administration of pembrolizumab for treatment of bladder cancer: A novel strategy to minimize toxicity.
Authors: Pradeep Tyagi, Anirban B. Ganguly, Jason Hafron, Jonathan Kaufman, Michael Chancellor
Journal: Journal of Clinical Oncology (2024)

e14687 Background: A major hallmark of bladder cancer (BCa) is a higher treatment success rate than prostate cancer following stimulation of innate anti-tumor immune response either by intravesical BCG or to FDA approved intravenous anti-PD1 checkpoint antibody (pembrolizumab) approved for BCG resistant BCa since 2021. However, injected pembrolizumab is characterized by a markedly higher incidence (66%) of serious adverse events than the median duration of complete response of ~40% for non-muscle invasive BCa (NMIBC) and 15-20% for invasive BCa. Since the toxicity (fatigue, Pneumonitis and diarrhea) of injected pembrolizumab is linked to systemic breakdown of T-cell mediated immune surveillance we enquired whether analogous to BCG, pembrolizumab can be administered intravesically to safely induce a localized anti-tumor response in mouse model of BCa. Methods: Six weeks old female mice of B6D2F1 strain (n=10) were ad libitum fed carcinogen, N-butyl-N-4-hydroxybutyl nitrosamine (BBN) in drinking water (0.05% w/v) for 12 weeks. The presence of BBN evoked tumor was ascertained by unenhanced T2 weighted MRI at week 11 prior to single intravesical dosing by 24G transurethral catheter under isoflurane anesthesia of 0.1mL vehicle (sterile water) with or without 0.3mg of Pembrolizumab (Lipella Pharmaceuticals). 6 weeks later, T2 weighted MRI was repeated together with T1 mapping by ICE-MRI prior to organ harvest. Results: BBN feeding evoked multiclonal tumors (red*) of comparable size on T2 weighted MRI at week 11 but repeat MRI 7 weeks after treatment revealed that tumor progression and perivesical invasion noted in vehicle group was arrested in pembrolizumab group. Longest dimension of BBN tumor in vehicle treated mice was ≥ 1mm longer (p&lt;0.05) than in pembrolizumab treated mice. T1 mapping revealed thickened bladder wall missed by T2 MRI. Conclusions: These findings on single intravesical dose of pembrolizumab (10mg/kg) in mice are consistent with human study on multiple intravesical dosing of BCG plus pembrolizumab (1-2mg/kg) in BCG resistant NMIBC patients. Intravesical pembrolizumab mirrors the limited systemic uptake of radiolabelled antibodies together with substantially higher ingress into tumor foci. The tumor selective ingress for BCa immunotherapy without any toxicity will be enhanced with Lipella Pharmaceutical’s liposomal delivery of Pembrolizumab.
Cognitive control training with domain-general response inhibition does not change children’s brains or behavior
Authors: Keertana Ganesan, Abigail Thompson, Claire R. Smid, Roser Cañigueral, Yongjing Li, Grace Revill, Vanessa Puetz, Boris C. Bernhardt, Nico U. F. Dosenbach, Rogier Kievit, Nikolaus Steinbeis
Journal: Nature Neuroscience (2024)

Abstract Cognitive control is required to organize thoughts and actions and is critical for the pursuit of long-term goals. Childhood cognitive control relates to other domains of cognitive functioning and predicts later-life success and well-being. In this study, we used a randomized controlled trial to test whether cognitive control can be improved through a pre-registered 8-week intervention in 235 children aged 6–13 years targeting response inhibition and whether this leads to changes in multiple behavioral and neural outcomes compared to a response speed training. We show long-lasting improvements of closely related measures of cognitive control at the 1-year follow-up; however, training had no impact on any behavioral outcomes (decision-making, academic achievement, mental health, fluid reasoning and creativity) or neural outcomes (task-dependent and intrinsic brain function and gray and white matter structure). Bayesian analyses provide strong evidence of absent training effects. We conclude that targeted training of response inhibition does little to change children’s brains or their behavior.