tbuckley/cabot-search huggingface dataset:
Responsible development of clinical speech AI: Bridging the gap between clinical research and technology
Authors: Visar Berisha, Julie M. Liss
Journal: npj Digital Medicine (2024)

This perspective article explores the challenges and potential of using speech as a biomarker in clinical settings, particularly when constrained by the small clinical datasets typically available in such contexts. We contend that by integrating insights from speech science and clinical research, we can reduce sample complexity in clinical speech AI models with the potential to decrease timelines to translation. Most existing models are based on high-dimensional feature representations trained with limited sample sizes and often do not leverage insights from speech science and clinical research. This approach can lead to overfitting, where the models perform exceptionally well on training data but fail to generalize to new, unseen data. Additionally, without incorporating theoretical knowledge, these models may lack interpretability and robustness, making them challenging to troubleshoot or improve post-deployment. We propose a framework for organizing health conditions based on their impact on speech and promote the use of speech analytics in diverse clinical contexts beyond cross-sectional classification. For high-stakes clinical use cases, we advocate for a focus on explainable and individually-validated measures and stress the importance of rigorous validation frameworks and ethical considerations for responsible deployment. Bridging the gap between AI research and clinical speech research presents new opportunities for more efficient translation of speech-based AI tools and advancement of scientific discoveries in this interdisciplinary space, particularly if limited to small or retrospective datasets.
Benchmarking clustering, alignment, and integration methods for spatial transcriptomics
Authors: Yunfei Hu, Manfei Xie, Yikang Li, Mingxing Rao, Wenjun Shen, Can Luo, Haoran Qin, Jihoon Baek, Xin Maizie Zhou
Journal: Genome biology (2024)

Spatial transcriptomics (ST) is advancing our understanding of complex tissues and organisms. However, building a robust clustering algorithm to define spatially coherent regions in a single tissue slice and aligning or integrating multiple tissue slices originating from diverse sources for essential downstream analyses remains challenging. Numerous clustering, alignment, and integration methods have been specifically designed for ST data by leveraging its spatial information. The absence of comprehensive benchmark studies complicates the selection of methods and future method development.
Genomic Determinants of Outcome in Acute Lymphoblastic Leukemia
Authors: Ti-Cheng Chang, Wenan Chen, Chunxu Qu, Zhongshan Cheng, Dale Hedges, Abdelrahman Elsayed, Stanley B. Pounds, Mary Shago, Karen R. Rabin, Elizabeth A. Raetz, Meenakshi Devidas, Cheng Cheng, Anne Angiolillo, Pradyuamna Baviskar, Michael Borowitz, Michael J. Burke, Andrew Carroll, William L. Carroll, I-Ming Chen, Richard Harvey, Nyla Heerema, Ilaria Iacobucci, Jeremy R. Wang, Sima Jeha, Eric Larsen, Leonard Mattano, Kelly Maloney, Ching-Hon Pui, Nilsa C. Ramirez, Wanda Salzer, Cheryl Willman, Naomi Winick, Brent Wood, Stephen P. Hunger, Gang Wu, Charles G. Mullighan, Mignon L. Loh
Journal: Journal of Clinical Oncology (2024)

Although cure rates for childhood acute lymphoblastic leukemia (ALL) exceed 90%, ALL remains a leading cause of cancer death in children. Half of relapses arise in children initially classified with standard-risk (SR) disease.
Molecular and Clinicopathologic Impact of GNAS Variants Across Solid Tumors
Authors: Paul Johannet, Somer Abdelfattah, Callahan Wilde, Shrey Patel, Henry Walch, Benoit Rousseau, Guillem Argiles, Oliver Artz, Miteshkumar Patel, Andrea Arfe, Andrea Cercek, Rona Yaeger, Karuna Ganesh, Nikolaus Schultz, Luis A. Diaz, Michael B. Foote
Journal: Journal of Clinical Oncology (2024)

PURPOSE The molecular drivers underlying mucinous tumor pathogenicity are poorly understood. GNAS mutations predict metastatic burden and treatment resistance in mucinous appendiceal adenocarcinoma. We investigated the pan-cancer clinicopathologic relevance of GNAS variants. METHODS We assessed 58,043 patients with Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (IMPACT)–sequenced solid tumors to identify oncogenic variants, including GNAS , associated with mucinous tumor phenotype. We then performed comprehensive molecular analyses to compare GNAS- mutant (mut) and wild-type tumors across cancers. Gene expression patterns associated with GNAS- mut tumors were assessed in a The Cancer Genome Atlas cohort. Associations between GNAS variant status and peritoneal metastasis, first-line systemic therapy response, progression-free survival (PFS), and overall survival (OS) were determined using a propensity-matched subcohort of patients with metastatic disease. RESULTS Mucinous tumors were enriched for oncogenic GNAS variants. GNAS was mutated in &gt;1% of small bowel, cervical, colorectal, pancreatic, esophagogastric, hepatobiliary, and GI neuroendocrine cancers. Across these cancers, GNAS- mut tumors exhibited a generally conserved C-to-T mutation-high, aneuploidy-low molecular profile with co-occurring prevalent KRAS variants (65% of GNAS-mut tumors) and fewer TP53 alterations. GNAS- mut tumors exhibited recurrently comutated alternative tumor suppressors ( RBM10 , INPPL1 ) and upregulation of MAPK and cell surface modulators. GNAS- mut tumors demonstrate an increased prevalence of peritoneal metastases (odds ratio [OR], 1.7 [95% CI, 1.1 to 2.5]; P = .006), worse response to first-line systemic therapy (OR, 2.2 [95% CI, 1.3 to 3.8]; P = .003), and shorter PFS (median, 5.6 v 7.0 months; P = .047). In a multivariable analysis, GNAS mutated status was independently prognostic of worse OS (hazard ratio, 1.25 [95% CI, 1.01 to 1.56]; adjusted P = .04). CONCLUSION Across the assessed cancers, GNAS- mut tumors exhibit a conserved molecular and clinical phenotype defined by mucinous tumor status, increased peritoneal metastasis, poor response to first-line systemic therapy, and worse survival.
SGLT2 inhibitors: a novel therapy for cognitive impairment via multifaceted effects on the nervous system
Authors: Jiaqi Mei, Yi Li, Liyan Niu, Ruikai Liang, Mingyue Tang, Qi Cai, Jingdong Xu, Deju Zhang, Xiaoping Yin, Xiao Liu, Yunfeng Shen, Jianping Liu, Minxuan Xu, Panpan Xia, Jitao Ling, Yuting Wu, Jianqi Liang, Jing Zhang, Peng Yu
Journal: Translational Neurodegeneration (2024)

The rising prevalence of diabetes mellitus has casted a spotlight on one of its significant sequelae: cognitive impairment. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, originally developed for diabetes management, are increasingly studied for their cognitive benefits. These benefits may include reduction of oxidative stress and neuroinflammation, decrease of amyloid burdens, enhancement of neuronal plasticity, and improved cerebral glucose utilization. The multifaceted effects and the relatively favorable side-effect profile of SGLT2 inhibitors render them a promising therapeutic candidate for cognitive disorders. Nonetheless, the application of SGLT2 inhibitors for cognitive impairment is not without its limitations, necessitating more comprehensive research to fully determine their therapeutic potential for cognitive treatment. In this review, we discuss the role of SGLT2 in neural function, elucidate the diabetes-cognition nexus, and synthesize current knowledge on the cognitive effects of SGLT2 inhibitors based on animal studies and clinical evidence. Research gaps are proposed to spur further investigation.
Drug induced cholestatic liver diseases
Authors: Einar S. Bjornsson, Harshad C. Devarbhavi
Journal: Hepatology (2024)

Cholestatic DILI is an important and frequently challenging differential diagnosis in patients presenting with elevated liver tests with predominant elevation in alkaline phosphatase. A number of competing etiologies need to be ruled out, such as hepatobiliary malignancy, choledocholithiasis, cholestatic forms of viral hepatitis, cholestasis of sepsis, primary and secondary cholangitis, and right-sided cardiac failure to name a few. Important advances have occurred in the understanding and knowledge of the clinical phenotypes, new etiological agents, risk factors, pathophysiology, and genetic determinants of drug-induced cholestasis since the last review on drug-induced cholestasis was published in Hepatology in 2011. Secondary sclerosing cholangitis (SSC) due to drugs has been well documented for several different drugs. Checkpoint inhibitors are one of the types of drugs shown to lead to secondary sclerosing cholangitis. Several new herbal and dietary supplements have recently been shown to lead to cholestatic liver injury. A number of genetic risk factors for cholestasis due to drugs have been identified in the last decade, and the pathogenesis behind cholestatic injury is better defined. In this review, the focus is on diagnostic approach and description of new clinical phenotypes such as secondary sclerosing cholangitis and vanishing bile duct syndrome. Furthermore, the review provides an overview of the risk factors, genetic determinants, and the pathophysiology of hepatobiliary transporters leading to cholestasis. Management, areas of uncertainty, and future direction are also presented.
The human CD47 checkpoint is targeted by an immunosuppressive <i>Aedes aegypti</i> salivary factor to enhance arboviral skin infectivity
Authors: Alejandro Marin-Lopez, John D. Huck, Allen T. Esterly, Veronica Azcutia, Connor Rosen, Rolando Garcia-Milian, Esen Sefik, Gemma Vidal-Pedrola, Hamidah Raduwan, Tse-Yu Chen, Gunjan Arora, Stephanie Halene, Albert C. Shaw, Noah W. Palm, Richard A. Flavell, Charles A. Parkos, Saravanan Thangamani, Aaron M. Ring, Erol Fikrig
Journal: Science Immunology (2024)

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SARS-CoV-2 JN.1 variant evasion of IGHV3-53/3-66 B cell germlines
Authors: Ida Paciello, Giuseppe Maccari, Giulio Pierleoni, Federica Perrone, Giulia Realini, Marco Troisi, Gabriele Anichini, Maria Grazia Cusi, Rino Rappuoli, Emanuele Andreano
Journal: Science Immunology (2024)

The severe acute respiratory syndrome coronavirus 2 variant JN.1 recently emerged as the dominant variant despite having only one amino acid change on the spike (S) protein receptor binding domain (RBD) compared with the ancestral BA.2.86, which never represented more than 5% of global variants. To define at the molecular level the JN.1 ability to spread globally, we interrogated a panel of 899 neutralizing human monoclonal antibodies. Our data show that the single leucine-455-to-serine mutation in the JN.1 spike protein RBD unleashed the global spread of JN.1, likely occurring by elimination of more than 70% of the neutralizing antibodies mediated by IGHV3-53/3-66 germlines. However, the resilience of class 3 antibodies with low neutralization potency but strong Fc functions may explain the absence of JN.1 severe disease.
A case of response to combination treatment with TSA-DC-CTL immunotherapy and osimertinib in EGFR mutated advanced lung adenocarcinoma
Authors: Zhiyi Han, Tao Li, Heng Zhang, Kai Liang, Mingcong You, Mengdi Xu, Fan Bai, Tongmei Zhang
Journal: Molecular Cancer (2024)

This study details a case of a patient with advanced lung adenocarcinoma harboring an exon 19 deletion in the EGFR gene.
Ankle-GO score is associated with the probability of becoming coper after lateral ankle sprain: a 1-year prospective cohort study
Authors: Brice Picot, François Fourchet, Gauthier Rauline, Kinan Freiha, Erik Wikstrom, Ronny Lopes, Alexandre Hardy
Journal: British Journal of Sports Medicine (2024)

To analyse the association between Ankle-GO score during the return to sport process and the probability of becoming a coper 1 year after lateral ankle sprain (LAS). Copers were defined as patients returning to their preinjury sport without loss of function and reporting no episodes of reinjury or giving-way.
The road to a world-unified approach to the management of patients with gastric intestinal metaplasia: a review of current guidelines
Authors: Mario Dinis-Ribeiro, Shailja Shah, Hashem El-Serag, Matthew Banks, Noriya Uedo, Hisao Tajiri, Luiz Gonzaga Coelho, Diogo Libanio, Edith Lahner, Antonio Rollan, Jing-Yuan Fang, Leticia Moreira, Jan Bornschein, Peter Malfertheiner, Ernst J Kuipers, Emad M El-Omar
Journal: Gut (2024)

During the last decade, the management of gastric intestinal metaplasia (GIM) has been addressed by several distinct international evidence-based guidelines. In this review, we aimed to synthesise these guidelines and provide clinicians with a global perspective of the current recommendations for managing patients with GIM, as well as highlight evidence gaps that need to be addressed with future research.
Efficacy and safety of chiauranib in a combination therapy in platinum-resistant or refractory ovarian cancer: a multicenter, open-label, phase Ib and II study
Authors: Jin Li, Jihong Liu, Rutie Yin, Dongling Zou, Hong Zheng, Junning Cao, Zhendong Chen, Wei Sun, Yunong Gao, Songling Zhang, Linjuan Zeng, Ruifang An, Xianping Lu, Shuang Ye, Xiaohua Wu
Journal: Molecular Cancer (2024)

Platinum-resistant or refractory ovarian cancer is a highly lethal gynecologic disease with limited treatment options. Chiauranib is a novel small-molecule selective inhibitor, which could effectively target multiple pathways including Aurora B and CSF-1R to inhibit cell cycle process and improve anti-tumor immune function, as long as VEGF pathway for tumor extinction.
One in 5 Children Have Autism If Older Sibling Does Too
Authors: Samantha Anderer
Journal: JAMA (2024)

Roughly 20% of younger siblings of children with autism spectrum disorder (ASD) were later diagnosed themselves, a new study on familial recurrence of autism published in Pediatrics found. For infants with more than 1 older sibling with autism, the likelihood of ASD rose to about 37%.
Economic Costs Attributed to Diagnosed Diabetes in Each U.S. State and the District of Columbia: 2021
Authors: Olga A. Khavjou, Minglu Sun, Sophia R. D’Angelo, Simon J. Neuwahl, Thomas J. Hoerger, Pyone Cho, Kristopher Myers, Ping Zhang
Journal: Diabetes Care (2024)

To update state-specific estimates of diabetes-attributable costs in the U.S. and assess changes in spending from 2013 to 2021.
Identification of endothelial protein C receptor as a novel druggable agonistic target for reendothelialization promotion and thrombosis prevention of eluting stent
Authors: Jing Chen, Changyi Zhou, Weilun Fang, Jiasheng Yin, Jian Shi, Junbo Ge, Li Shen, Shi-Ming Liu, Shao-Jun Liu
Journal: Bioactive Materials (2024)

The commercially available drug-eluting stent with limus (rapamycin, everolimus, etc.) or paclitaxel inhibits smooth muscle cell (SMC), reducing the in-stent restenosis, whereas damages endothelial cell (EC) and delays stent reendothelialization, increasing the risk of stent thrombosis (ST) and sudden cardiac death. Here we present a new strategy for promoting stent reendothelialization and preventing ST by exploring the application of precise molecular targets with EC specificity. Proteomics was used to investigate the molecular mechanism of EC injury caused by rapamycin. Endothelial protein C receptor (EPCR) was screened out as a crucial EC-specific effector. Limus and paclitaxel repressed the EPCR expression, while overexpression of EPCR protected EC from coating (eluting) drug-induced injury. Furthermore, the ligand activated protein C (APC), polypeptide TR47, and compound parmodulin 2, which activated the target EPCR, promoted EC functions and inhibited platelet or neutrophil adhesion, and enhanced rapamycin stent reendothelialization in the simulated stent environment and in vitro. In vivo, the APC/rapamycin-coating promoted reendothelialization rapidly and prevented ST more effectively than rapamycin-coating alone, in both traditional metal stents and biodegradable stents. Additionally, overexpression or activation of the target EPCR did not affect the cellular behavior of SMC or the inhibitory effect of rapamycin on SMC. In conclusion, EPCR is a promising therapeutical agonistic target for pro-reendothelialization and anti-thrombosis of eluting stent. Activation of EPCR protects against coating drugs-induced EC injury, inflammatory cell, or platelet adhesion onto the stent. The novel application formula for APC/rapamycin-combined eluting promotes stent reendothelialization and prevents ST.
Universal Free School Meals and School and Student Outcomes
Authors: Maureen K. Spill, Rupal Trivedi, Rachel C. Thoerig, Arin A. Balalian, Marlene B. Schwartz, Craig Gundersen, Angela Odoms-Young, Elizabeth F. Racine, Margaret J. Foster, Julie S. Davis, Amanda J. MacFarlane
Journal: JAMA Network Open (2024)

Importance The White House National Strategy on Hunger, Nutrition, and Health included expanding free school meals to all students, regardless of income, which has sparked debate in the United States. Objective To assess the association between universal free school meals (UFSMs) and school and student outcomes in the United States. Evidence Review An expert panel–informed protocol was developed to evaluate intervention or cohort studies comparing UFSM programs, such as the Community Eligibility Provision (CEP), with non-UFSM programs in US schools from August 2012 (excluding 2020-2021 due to the COVID-19 pandemic) in peer-reviewed publications or government reports. Outcomes included meal participation rates, attendance, dietary intake and quality, food waste, economic impact, food insecurity, anthropometrics, disciplinary actions, stigma, and shaming. A search of Medline, Econlit, Business Source Ultimate, ERIC, Agricola, Cab Abstracts, and CINAHL was performed in April 2024. Two researchers screened articles for inclusion, extracted data, and assessed risk of bias, using the Risk of Bias in Nonrandomized Studies of Interventions tool, for each included study. Grading of Recommendations, Assessment, Development, and Evaluations was used to assess the certainty of evidence for each outcome. Findings The search identified 2784 records, with 6 studies included, representing more than 11 000 elementary, middle, and high schools. Nonrandomized intervention studies performed difference-in-difference or rate ratio analysis to investigate CEP participation rates, attendance, anthropometrics, and/or suspensions. CEP was associated with increased lunch (3 studies; moderate certainty) and breakfast (1 study; very low certainty) participation. School attendance was unchanged or improved in schools with CEP compared with schools without UFSM (2 studies; low certainty). CEP was associated with lower obesity prevalence (1 study; very low certainty) and fewer suspensions (1 study; very low certainty). Reasons for downgrading the certainty ratings included indirectness (data not fully representative of the United States) and inconsistency (small number of studies limiting ability to assess consistency). Despite the limitations, the evidence reflected well-designed longitudinal intervention studies appropriate for decision-making. Conclusions and Relevance In this systematic review, UFSMs were associated with increased meal participation, no or slight improvements in attendance, and decreased obesity prevalence and suspension rates; certainty of evidence was moderate for lunch participation and low or very low for other outcomes. Studies did not report several important outcomes, such as diet quality and food security, suggesting the need for more high-quality research encompassing policy-relevant indicators.
Psychological Factors, Physical Conditions, and Functioning Among US Veterans
Authors: Ian C. Fischer, Peter J. Na, David B. Feldman, Alex H. Krist, Harold S. Kudler, Dilip V. Jeste, Robert H. Pietrzak
Journal: JAMA Network Open (2024)

This cross-sectional study examines the association of protective psychological characteristics with mental, psychosocial, cognitive, and physical functioning in military veterans.
Less Screen Time Linked to Improved Sociability and Behavior in Children
Authors: Samantha Anderer
Journal: JAMA (2024)

Jesper Schmidt-Persson, PhD; Martin Gillies Banke Rasmussen, PhD; Sarah Overgaard Sørensen, MSc; Sofie Rath Mortensen, MSc; Line Grønholt Olesen, PhD; Søren Brage, PhD; Peter Lund Kristensen, PhD; Niels Bilenberg, PhD; Anders Grøntved, PhD
A Protocol for the Inclusion of Minoritized Persons in Alzheimer Disease Research From the ADNI3 Diversity Taskforce
Authors: Ozioma C. Okonkwo, Monica Rivera Mindt, Miriam T. Ashford, Catherine Conti, Joe Strong, Rema Raman, Michael C. Donohue, Rachel L. Nosheny, Derek Flenniken, Melanie J. Miller, Adam Diaz, Annabelle M. Soto, Beau M. Ances, Maryam R. Beigi, P. Murali Doraiswamy, Ranjan Duara, Martin R. Farlow, Hillel T. Grossman, Jacobo E. Mintzer, Christopher Reist, Emily J. Rogalski, Marwan N. Sabbagh, Stephen Salloway, Lon S. Schneider, Raj C. Shah, Ronald C. Petersen, Paul S. Aisen, Michael W. Weiner
Journal: JAMA Network Open (2024)

Black or African American (hereinafter, Black) and Hispanic or Latino/a/x (hereinafter, Latinx) adults are disproportionally affected by Alzheimer disease, but most research studies do not enroll adequate numbers of both of these populations. The Alzheimer's Disease Neuroimaging Initiative-3 (ADNI3) launched a diversity taskforce to pilot a multipronged effort to increase the study inclusion of Black and Latinx older adults. To describe and evaluate the culturally informed and community-engaged inclusion efforts to increase the screening and enrollment of Black and Latinx older adults in ADNI3. This cross-sectional study used baseline data from a longitudinal, multisite, observational study conducted from January 15, 2021, to July 12, 2022, with no follow-up. The study was conducted at 13 ADNI3 sites in the US. Participants included individuals aged 55 to 90 years without cognitive impairment and those with mild cognitive impairment or Alzheimer disease. Efforts included (1) launch of an external advisory board, (2) changes to the study protocol, (3) updates to the digital prescreener, (4) selection and deployment of 13 community-engaged research study sites, (5) development and deployment of local and centralized outreach efforts, and (6) development of a community-science partnership board. Screening and enrollment numbers from centralized and local outreach efforts, digital advertisement metrics, and digital prescreener completion. A total of 91 participants enrolled in the trial via centralized and local outreach efforts, of which 22 (24.2%) identified as Latinx and 55 (60.4%) identified as Black (median [IQR] age, 65.6 [IQR, 61.5-72.5] years; 62 women [68.1%]). This represented a 267.6% increase in the monthly rate of enrollment (before: 1.11 per month; during: 4.08 per month) of underrepresented populations. For the centralized effort, social media advertisements were run between June 1, 2021, and July 31, 2022, which resulted in 2079 completed digital prescreeners, of which 1289 met criteria for subsequent site-level screening. Local efforts were run between June 1, 2021, to July 31, 2022. A total of 151 participants underwent site-level screening (100 from local efforts, 41 from centralized efforts, 10 from other sources). In this cross-sectional study of pilot inclusion efforts, a culturally informed, community-engaged approach increased the inclusion of Black and Latinx participants in an Alzheimer disease cohort study.
The PACT Act—Expanding Coverage and Access for Veterans
Authors: Adam L. Beckman, Joshua Jacobs, Shereef M. Elnahal
Journal: JAMA (2024)

This Viewpoint examines the implementation of the Sergeant First Class Heath Robinson Honoring Our Promise to Address Comprehensive Toxics Act, known as the PACT Act, which expanded health care for millions of veterans from any era exposed to toxic hazards.