tbuckley/cabot-search huggingface dataset:
<i>Clostridium innocuum</i> , an opportunistic gut pathogen, inactivates host gut progesterone and arrests ovarian follicular development
Authors: Mei-Jou Chen, Chia-Hung Chou, Tsun-Hsien Hsiao, Tien-Yu Wu, Chi-Ying Li, Yi-Lung Chen, Kuang-Han Chao, Tzong-Huei Lee, Ronnie G. Gicana, Chao-Jen Shih, Guo-Jie Brandon-Mong, Yi-Li Lai, Po-Ting Li, Yu-Lin Tseng, Po-Hsiang Wang, Yin-Ru Chiang
Journal: Gut Microbes (2024)

\Levels of progesterone, an endogenous female hormone, increase after ovulation; progesterone is crucial in the luteal phase to maintain successful pregnancy and prevent early miscarriage. Both endogenous and exogenous progesterone are recycled between the liver and gut; thus, the gut microbiota regulate host progesterone levels by inhibiting enterohepatic progesterone circulation. Our data indicated
PPARα exacerbates <i>Salmonella</i> Typhimurium infection by modulating the immunometabolism and macrophage polarization
Authors: Jessica R. Taddeo, Naomi Wilson, Anita Kowal, Joris Beld, Klein-Szanto Andres, Çagla Tükel, Vincent C. Tam
Journal: Gut Microbes (2024)

Typhimurium (STm) is a causative pathogen for robust inflammatory gastrointestinal disease and can lead to systemic infection. Eicosanoids, bioactive lipid mediators, play a crucial role in modulating both the induction and resolution of inflammatory responses during an infection. A subset of eicosanoids activates PPARs, nuclear receptor/transcription factors that regulate fatty acid metabolism, lipid body formation, and macrophage function. In this study, we determined that mice lacking PPARα exhibited reduced inflammatory hallmarks of STm infection, including lower inflammatory gene expression, cecal inflammation, and bacterial dissemination, along with a significant increase in cecal eicosanoid metabolism compared to wildtype C57BL/6 mice. In macrophages, STm favored M2b-polarized macrophages for intracellular infection, leading to reduced arachidonic acid and ceramide production. Inhibition of fatty acid oxidation via Etomoxir in STm-infected macrophages reduced bacterial burdens and promoted cell death. In Etomoxir-treated wildtype mice, STm infection increased ceramide production, decreased inflammatory gene expression in the cecum, and increased the number of STm-containing M1 macrophages in mesenteric lymph nodes. These findings revealed a novel role for the lipid-immune signaling axis in
The association of bearing surface materials with the risk of revision following primary total hip replacement: A cohort analysis of 1,026,481 hip replacements from the National Joint Registry
Authors: Michael R. Whitehouse, Rita Patel, Jonathan M. R. French, Andrew D. Beswick, Patricia Navvuga, Elsa M. R. Marques, Ashley W. Blom, Erik Lenguerrand
Journal: PLoS Medicine (2024)

The risk of re-operation, otherwise known as revision, following primary hip replacement depends in part on the prosthesis implant materials used. Current performance evidences are based on a broad categorisation grouping together different materials with potentially varying revision risks. We investigated the revision rate of primary total hip replacement (THR) reported in the National Joint Registry by specific types of bearing surfaces used.
Personal Protective Equipment Use by Dairy Farmworkers Exposed to Cows Infected with Highly Pathogenic Avian Influenza A(H5N1) Viruses — Colorado, 2024
Authors: Kristen E. Marshall, Cara C. Drehoff, Nisha Alden, Sophia Montoya, Ginger Stringer, Allison Kohnen, Alexandra Mellis, Sascha Ellington, Jordan Singleton, Carrie Reed, Rachel Herlihy, Rachel Alade, Marlee Barton, Cindy Camarillo, Lauren Duval, Rebecca Hermann, Frankie Lupercio, Leovi Madera, Pamela Pagano, Jeannette Rodriguez
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

The risk for transmission of highly pathogenic avian influenza A(H5N1) virus from dairy cows to humans is currently low; however, personal protective equipment (PPE) use during work activities on dairy farms has not been well described. PPE use can protect farmworkers when they are working with highly pathogenic avian influenza A(H5N1)-infected cows. The Colorado Department of Public Health and Environment (CDPHE) and the Colorado Department of Agriculture (CDA) offered PPE to all Colorado farms before or during an A(H5N1) outbreak in cows in 2024. CDPHE surveyed 83 dairy workers from three farms with a confirmed bovine A(H5N1) outbreak. Frequently reported farm worker activities included milking cows or working in the milking parlor (51%), cleaning cow manure (49%), and transporting cows (46%). Frequently reported PPE items available to workers before A(H5N1) outbreaks included gloves (88%), eye protection (e.g., safety glasses or goggles) (76%), rubber boots or boot covers (71%), and head covers (69%). N95 respirator use was low among workers who were exposed to ill cows after detection of A(H5N1) virus (26%). PPE use while working with ill cows increased a mean of 28% after detection of A(H5N1) virus on surveyed farms; use of eye protection while milking cows increased the most (40%). Public health PPE distribution, education, and collaboration with CDA might have increased PPE use on dairy farms with A(H5N1) virus-infected cows and mitigated risk for farmworkers acquiring A(H5N1) virus.
GraphPCA: a fast and interpretable dimension reduction algorithm for spatial transcriptomics data
Authors: Jiyuan Yang, Lu Wang, Lin Liu, Xiaoqi Zheng
Journal: Genome biology (2024)

The rapid advancement of spatial transcriptomics technologies has revolutionized our understanding of cell heterogeneity and intricate spatial structures within tissues and organs. However, the high dimensionality and noise in spatial transcriptomic data present significant challenges for downstream data analyses. Here, we develop GraphPCA, an interpretable and quasi-linear dimension reduction algorithm that leverages the strengths of graphical regularization and principal component analysis. Comprehensive evaluations on simulated and multi-resolution spatial transcriptomic datasets generated from various platforms demonstrate the capacity of GraphPCA to enhance downstream analysis tasks including spatial domain detection, denoising, and trajectory inference compared to other state-of-the-art methods.
Progress Toward Global Dracunculiasis (Guinea Worm Disease) Eradication, January 2023–June 2024
Authors: Donald R. Hopkins, Adam J. Weiss, Sarah Yerian, Yujing Zhao, Sarah G.H. Sapp, Vitaliano A. Cama
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

The effort to eradicate Dracunculus medinensis, the etiologic agent of dracunculiasis, or Guinea worm disease, began at CDC in 1980. In 1986, with an estimated 3.5 million global cases in 20 African and Asian countries, the World Health Assembly called for dracunculiasis elimination. The Guinea Worm Eradication Program (GWEP) was established to help countries with endemic dracunculiasis reach this goal. GWEP is led by The Carter Center and supported by partners, including the countries with endemic disease, CDC, UNICEF, and the World Health Organization. Since 2012, infections in dogs, cats, and baboons have posed a new challenge for GWEP, as have ongoing civil unrest and insecurity in some areas. As of June 2024, dracunculiasis remained endemic in five countries (Angola, Chad, Ethiopia, Mali, and South Sudan). Fourteen human cases and 886 animal infections occurred, including 407 dogs in Chad and 248 dogs in Cameroon, reported in 2023, and three human cases and 297 animal infections reported during January-June 2024. Animal infections, primarily in dogs in Cameroon and Chad, and impeded access due to civil unrest and insecurity in Mali, threaten the near-term possibility of global eradication. Nevertheless, countries appear poised to reach zero cases.
Serologic Evidence of Recent Infection with Highly Pathogenic Avian Influenza A(H5) Virus Among Dairy Workers — Michigan and Colorado, June–August 2024
Authors: Alexandra M. Mellis, Joseph Coyle, Kristen E. Marshall, Aaron M. Frutos, Jordan Singleton, Cara Drehoff, Angiezel Merced-Morales, H. Pamela Pagano, Rachel O. Alade, Elizabeth B. White, Emma K. Noble, Crystal Holiday, Feng Liu, Stacie Jefferson, Zhu-Nan Li, F. Liani Gross, Sonja J. Olsen, Vivien G. Dugan, Carrie Reed, Sascha Ellington, Sophia Montoya, Allison Kohnen, Ginger Stringer, Nisha Alden, Peter Blank, Derick Chia, Natasha Bagdasarian, Rachel Herlihy, Sarah Lyon-Callo, Min Z. Levine
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

Since April 2024, sporadic infections with highly pathogenic avian influenza (HPAI) A(H5) viruses have been detected among dairy farm workers in the United States. To date, infections have mostly been detected through worker monitoring, and have been mild despite the possibility of more severe illness. During June-August 2024, CDC collaborated with the Michigan Department of Health and Human Services and the Colorado Department of Public Health and Environment to implement cross-sectional serologic surveys to ascertain the prevalence of recent infection with HPAI A(H5) virus among dairy workers. In both states, a convenience sample of persons who work in dairies was interviewed, and blood specimens were collected. Among 115 persons, eight (7%; 95% CI = 3.6%-13.1%) had serologic evidence of recent infection with A(H5) virus; all reported milking cows or cleaning the milking parlor. Among persons with serologic evidence of infection, four recalled being ill around the time cows were ill; symptoms began before or within a few days of A(H5) virus detections among cows. This finding supports the need to identify and implement strategies to prevent transmission among dairy cattle to reduce worker exposures and for education and outreach to dairy workers concerning prevention, symptoms, and where to seek medical care if the workers develop symptoms. Timely identification of infected herds can support rapid initiation of monitoring, testing, and treatment for human illness, including mild illness, among exposed dairy workers.
Hemophagocytic lymphohistiocytosis: current treatment advances, emerging targeted therapy and underlying mechanisms
Authors: Yijun Wu, Xu Sun, Kai Kang, Yuqi Yang, He Li, Ailin Zhao, Ting Niu
Journal: Journal of Hematology & Oncology (2024)

Hemophagocytic lymphohistiocytosis (HLH) is a rapidly progressing, life-threatening syndrome characterized by excessive immune activation, often presenting as a complex cytokine storm. This hyperactive immune response can lead to multi-organ failure and systemic damage, resulting in an extremely short survival period if left untreated. Over the past decades, although HLH has garnered increasing attention from researchers, there have been few advancements in its treatment. The cytokine storm plays a crucial role in the treatment of HLH. Investigating the detailed mechanisms behind cytokine storms offers insights into targeted therapeutic approaches, potentially aiding in early intervention and improving the clinical outcome of HLH patients. To date, there is only one targeted therapy, emapalumab targeting interferon-γ, that has gained approval for primary HLH. This review aims to summarize the current treatment advances, emerging targeted therapeutics and underlying mechanisms of HLH, highlighting its newly discovered targets potentially involved in cytokine storms, which are expected to drive the development of novel treatments and offer fresh perspectives for future studies. Besides, multi-targeted combination therapy may be essential for disease control, but further trials are required to determine the optimal treatment mode for HLH.
Collaboration between clinicians and vision–language models in radiology report generation
Authors: Ryutaro Tanno, David G. T. Barrett, Andrew Sellergren, Sumedh Ghaisas, Sumanth Dathathri, Abigail See, Johannes Welbl, Charles Lau, Tao Tu, Shekoofeh Azizi, Karan Singhal, Mike Schaekermann, Rhys May, Roy Lee, SiWai Man, Sara Mahdavi, Zahra Ahmed, Yossi Matias, Joelle Barral, S. M. Ali Eslami, Danielle Belgrave, Yun Liu, Sreenivasa Raju Kalidindi, Shravya Shetty, Vivek Natarajan, Pushmeet Kohli, Po-Sen Huang, Alan Karthikesalingam, Ira Ktena
Journal: Nature Medicine (2024)

Automated radiology report generation has the potential to improve patient care and reduce the workload of radiologists. However, the path toward real-world adoption has been stymied by the challenge of evaluating the clinical quality of artificial intelligence (AI)-generated reports. We build a state-of-the-art report generation system for chest radiographs, called Flamingo-CXR, and perform an expert evaluation of AI-generated reports by engaging a panel of board-certified radiologists. We observe a wide distribution of preferences across the panel and across clinical settings, with 56.1% of Flamingo-CXR intensive care reports evaluated to be preferable or equivalent to clinician reports, by half or more of the panel, rising to 77.7% for in/outpatient X-rays overall and to 94% for the subset of cases with no pertinent abnormal findings. Errors were observed in human-written reports and Flamingo-CXR reports, with 24.8% of in/outpatient cases containing clinically significant errors in both report types, 22.8% in Flamingo-CXR reports only and 14.0% in human reports only. For reports that contain errors we develop an assistive setting, a demonstration of clinician-AI collaboration for radiology report composition, indicating new possibilities for potential clinical utility.
Engineered Cardiac Tissues as a Platform for CRISPR‐Based Mitogen Discovery
Authors: Sophia DeLuca, Nicholas Strash, Yifan Chen, Marisa Patsy, Ashley Myers, Libertad Tejeda, Sarah Broders, Amber Miranda, Xixian Jiang, Nenad Bursac
Journal: Advanced Healthcare Materials (2024)

Improved understanding of cardiomyocyte (CM) cell cycle regulation may allow researchers to stimulate pro-regenerative effects in injured hearts or promote maturation of human stem cell-derived CMs. Gene therapies, in particular, hold promise to induce controlled proliferation of endogenous or transplanted CMs via transient activation of mitogenic processes. Methods to identify and characterize candidate cardiac mitogens in vitro can accelerate translational efforts and contribute to the understanding of the complex regulatory landscape of CM proliferation and postnatal maturation. In this study, A CRISPR knockout-based screening strategy using in vitro neonatal rat ventricular myocyte (NRVM) monolayers is established, followed by candidate mitogen validation in mature 3-D engineered cardiac tissues (ECTs). This screen identified knockout of the purine metabolism enzyme adenosine deaminase (ADA-KO) as an effective pro-mitogenic stimulus. RNA-sequencing of ECTs further reveals increased pentose phosphate pathway (PPP) activity as the primary driver of ADA-KO-induced CM cycling. Inhibition of the pathway's rate limiting enzyme, glucose-6-phosphate dehydrogenase (G6PD), prevented ADA-KO induced CM cycling, while increasing PPP activity via G6PD overexpression increased CM cycling. Together, this study demonstrates the development and application of a genetic/tissue engineering platform for in vitro discovery and validation of new candidate mitogens affecting regenerative or maturation states of cardiomyocytes.
Proteasome inhibitors related thrombotic microangiopathy: a systematic and comprehensive review
Authors: Can Chen, Yiwei Li, Pengfei Shi, Shenxian Qian
Journal: Blood Cancer Journal (2024)

Proteasome inhibitors (PIs) are crucial in treating multiple myeloma but carry a risk of thrombotic microangiopathy (TMA), especially with carfilzomib use. This systematic review includes 44 studies with 115 cases of PI-induced TMA, where carfilzomib was implicated in 101 cases. Treatment approaches varied: 28 patients received supportive care, 43 underwent therapeutic plasma exchange (TPE), 9 were treated exclusively with eculizumab (ECU), and 13 received both TPE and ECU. Notably, eculizumab significantly improved outcomes for patients unresponsive to initial TPE, achieving complete remission in seven cases. The need for dialysis emerged as a significant predictor of outcomes, often indicating a poor prognosis. For patients suspected of having PI-TMA, it is advisable to discontinue the offending medication promptly, even without definitive laboratory confirmation. In cases where diagnosis is challenging, kidney biopsy may assist if conditions permit. Comprehensive evaluation of the complement system, including genetic mutations, function, and associated complement inhibitory factor antibodies, should be included in the assessment of PI-TMA. Early administration of eculizumab may be beneficial in cases of suspected complement abnormalities or suboptimal response to initial treatments.
Large-scale exome sequencing identified 18 novel genes for neuroticism in 394,005 UK-based individuals
Authors: Xin-Rui Wu, Ze-Yu Li, Liu Yang, Ying Liu, Chen-Jie Fei, Yue-Ting Deng, Wei-Shi Liu, Bang-Sheng Wu, Qiang Dong, Jian-Feng Feng, Wei Cheng, Jin-Tai Yu
Journal: Nature Human Behaviour (2024)
Is CAR T a drug or a therapeutic pathway? Intention to treat versus per protocol analysis of real world studies of CAR-T cell therapy in relapsed refractory diffuse large B cell lymphoma
Authors: Rossana Di Staso, Beatrice Casadei, Frederick L. Locke, Michael Jain, Timothy J. Voorhees, Adam S. Kittai, Mariana Bastos-Oreiro, Antonio Gutiérrez, Alejandro Martin Garcia-Sancho, Maria Jose Terol, Monica Mead, Michael J. Maranzano, Gloria Iacoboni, Pere Barba, Mi Kwon, Rebeca Bailen, Juan Luis Reguera-Ortega, Agrima Mian, Brian Hill, Emmanuel Bachy, Franck Morschhauser, Roch Houot, Catherine Thieblemont, Steven Le Gouill, Riccardo Masetti, Davide Gori, Alessandro Broccoli, Pier Luigi Zinzani, Lisa Argnani
Journal: Blood Cancer Journal (2024)
Safety, clinical activity, pharmacodynamics, and pharmacokinetics of IMU-856, a SIRT6 modulator, in coeliac disease: a first-in-human, randomised, double-blind, placebo-controlled, phase 1 trial
Authors: A James M Daveson, Richard Stubbs, Thomas M Polasek, Jorma Isola, Robert Anderson, Jason A Tye-Din, Mark Schoeman, Claudette Lionnet, Swee Lin Chen Yi Mei, Jelena Mihajlović, Martina Wirth, Evelyn Peelen, Amelie Schreieck, Hella Kohlhof, Daniel Vitt, Andreas Muehler, Franziska Buriánek
Journal: The Lancet. Gastroenterology & hepatology (2024)
TB or not TB: does AI have an answer for children?
Authors: Jacob Creswell, Rachel L. Byrne, Tushar Garg
Journal: European Respiratory Journal (2024)

<title>Extract</title> In 2021, the World Health Organization (WHO) issued recommendations for the use of artificial intelligence (AI), affirming the technology could be used instead of human readers for the interpretation of chest radiograph (CXR) images for the screening and triage of tuberculosis (TB), marking a historic precedent for a guideline on AI in health [1]. The forward-looking guidance highlights the utility of CXR in TB, despite past reluctance from WHO to use it in TB programmes [2]. Employing CXR in a diagnostic algorithm can identify people with subclinical TB who are asymptomatic but have lung pathology suggestive of TB, and refer them for testing and diagnosis [3].
Decoding genetic susceptibility to<i>Pseudomonas aeruginosa</i>infections in cystic fibrosis
Authors: Anthony J. Fischer, Christina S. Thornton
Journal: European Respiratory Journal (2024)

<title>Extract</title> In cystic fibrosis (CF), <italic>Pseudomonas aeruginosa</italic> acquisition represents a turning point in disease progression. The presence of chronic <italic>P. aeruginosa</italic> infection is associated with worsening lung function and increased risk of earlier death, whereas treatment substantially improves lung function and survival [1, 2]. Efforts to diagnose and eradicate early <italic>P. aeruginosa</italic> provide lasting benefits for children with CF [3, 4]. However, the timing of infection varies considerably between individuals with CF, treatment centres [5, 6], and different birth cohorts of people with the disease [7, 8].
CPAP recall and cancer risk: should we be concerned?
Authors: Frédéric Gagnadoux, Sébastien Bailly, Richard J. Schwab
Journal: European Respiratory Journal (2024)

<title>Extract</title> There is an expanding literature on the association between obstructive sleep apnoea (OSA) and cancer risk [1, 2]. Evidence is growing from population- and clinic-based cohort studies that the severity of OSA and sleep-related hypoxaemia may adversely affect both overall cancer risk and incidence of certain cancers [3–7]. These clinical findings are supported by the identification of the intermediate mechanisms by which intermittent hypoxia and sleep fragmentation, the hallmark features of OSA, might promote oncogenesis, tumour growth and metastasis [8]. Although studies have shown a relationship between OSA and cancer, few have evaluated whether the risk of cancer development or progression in patients with OSA is modified by continuous positive airway pressure (CPAP) therapy (the primary treatment for OSA) [1, 2].
The treatment of latent tuberculosis infection in migrants in primary care<i>versus</i>secondary care
Authors: Srishti Chhabra, Matthew Chung Yi Koh, David Michael Allen
Journal: European Respiratory Journal (2024)

<title>Extract</title> With a disproportionate burden of tuberculosis (TB) amongst migrants in Europe [1], B<sc>urman</sc> <italic>et al.</italic> [2] have highlighted the pressing need for alternative approaches to make TB infection (TBI) screening comprehensive and accessible. Across high-income Organisation for Economic Co-operation and development countries, a median of 52% of TB cases occur in foreign-born individuals, who are at their highest risk of developing TB disease within the first 5 years of migration [3]. Molecular epidemiological studies indicate that the majority of these cases occur as a result of TBI reactivation, often acquired overseas [4]. Within the UK, overseas-born migrants have a 14-fold higher TB incidence than UK-born individuals [5]. The World Health Organization therefore recommends that migrants from countries with a high TB burden may be prioritised for TBI screening [6, 7].
Ensuring availability of respiratory medicines in times of European drug shortages
Authors: Job F.M. van Boven, Arzu Yorgancioglu, Nicolas Roche, Omar S. Usmani
Journal: European Respiratory Journal (2024)

<title>Extract</title> It is of utmost importance that medicines are available at all times for our patients. Historically, medication unavailability has typically, if not exclusively, affected low- and middle-income countries [1]. More recently however, drug shortages have also been reported in high-income European countries [2]. Drug shortages have negative health consequences for patients [3], and a profound economic impact, with the need to resort to more expensive alternatives and demands on healthcare professionals' time to find, prescribe and dispense alternatives [4].