tbuckley/cabot-search huggingface dataset:
What Is the Influence of HIV Serostatus on HbA1c? A Prospective Analysis Using Continuous Glucose Monitoring
Authors: Harriet Daultrey, Nick S. Oliver, Juliet Wright, Tom J. Levett, Ali Jason Chakera
Journal: Diabetes Care (2024)

OBJECTIVE Type 2 diabetes (T2D) is reported to be more common in people living with HIV (PLWH). Clinical guidelines recommend screening for diabetes in PLWH, but there is no agreed method due to studies reporting HbA1c is falsely low in PLWH. These studies were performed in the early HIV era when participants were taking older preparations of antiretroviral therapy that are rarely used today. We aimed to investigate whether HIV serostatus influences HbA1c. RESEARCH DESIGNS AND METHODS We conducted a prospective cohort study of PLWH and age- and sex-matched HIV-negative participants who were purposely recruited from clinics in Brighton, U.K. Each participant wore a Dexcom G6 continuous glucose monitor (CGM) for up to 10 days, had glucose measured during an oral glucose tolerance test, and fructosamine and paired HbA1c were measured. We performed regression analysis to assess the influence of HIV on HbA1c and used a separate model for CGM glucose, venous glucose, and fructosamine. In addition, we included predictor variables used in previous studies that explored HbA1c discrepancy. RESULTS We recruited 60 PLWH (90% men, 50% with T2D, mean ± SD age 57 ± 10.7 years, 100% undetectable viral load) and 48 people without HIV (92% men, 30% with T2D, mean age 57.7 ± 8.9 years). We found that HIV serostatus did not have a significant influence on HbA1c within the regression models. CONCLUSIONS We performed a comprehensive assessment of glycemia to assess whether HIV serostatus influences HbA1c. We did not find any strong evidence that HIV serostatus influenced HbA1c. The results of our study support incorporating HbA1c into routine clinical blood work in PLWH.
Progesterone for Neurodevelopment in Fetuses With Congenital Heart Defects
Authors: J. William Gaynor, Julie S. Moldenhauer, Erin E. Zullo, Nancy B. Burnham, Marsha Gerdes, Judy C. Bernbaum, Jo Ann D’Agostino, Rebecca L. Linn, Brenna Klepczynski, Isabel Randazzo, Gabrielle Gionet, Grace H. Choi, Antoneta Karaj, William W. Russell, Elaine H. Zackai, Mark P. Johnson, Juliana S. Gebb, Shelly Soni, Suzanne E. DeBari, Anita L. Szwast, Rebecca C. Ahrens-Nicklas, Theodore G. Drivas, Marin Jacobwitz, Daniel J. Licht, Arastoo Vossough, Susan C. Nicolson, Thomas L. Spray, Jack Rychik, Mary E. Putt
Journal: JAMA Network Open (2024)

Importance Neurodevelopmental outcomes for children with congenital heart defects (CHD) have improved minimally over the past 20 years. Objectives To assess the feasibility and tolerability of maternal progesterone therapy as well as the magnitude of the effect on neurodevelopment for fetuses with CHD. Design, Setting, and Participants This double-blinded individually randomized parallel-group clinical trial of vaginal natural progesterone therapy vs placebo in participants carrying fetuses with CHD was conducted between July 2014 and November 2021 at a quaternary care children’s hospital. Participants included maternal-fetal dyads where the fetus had CHD identified before 28 weeks’ gestational age and was likely to need surgery with cardiopulmonary bypass in the neonatal period. Exclusion criteria included a major genetic or extracardiac anomaly other than 22q11 deletion syndrome and known contraindication to progesterone. Statistical analysis was performed June 2022 to April 2024. Intervention Participants were 1:1 block-randomized to vaginal progesterone or placebo by diagnosis: hypoplastic left heart syndrome (HLHS), transposition of the great arteries (TGA), and other CHD diagnoses. Treatment was administered twice daily between 28 and up to 39 weeks’ gestational age. Main Outcomes and Measures The primary outcome was the motor score of the Bayley Scales of Infant and Toddler Development-III; secondary outcomes included language and cognitive scales. Exploratory prespecified subgroups included cardiac diagnosis, fetal sex, genetic profile, and maternal fetal environment. Results The 102 enrolled fetuses primarily had HLHS (n = 52 [50.9%]) and TGA (n = 38 [37.3%]), were more frequently male (n = 67 [65.7%]), and without genetic anomalies (n = 61 [59.8%]). The mean motor score differed by 2.5 units (90% CI, −1.9 to 6.9 units; P = .34) for progesterone compared with placebo, a value not statistically different from 0. Exploratory subgroup analyses suggested treatment heterogeneity for the motor score for cardiac diagnosis ( P for interaction = .03) and fetal sex ( P for interaction = .04), but not genetic profile ( P for interaction = .16) or maternal-fetal environment ( P for interaction = .70). Conclusions and Relevance In this randomized clinical trial of maternal progesterone therapy, the overall effect was not statistically different from 0. Subgroup analyses suggest heterogeneity of the response to progesterone among CHD diagnosis and fetal sex. Trial Registration ClinicalTrials.gov Identifier: NCT02133573
Air and Noise Pollution Exposure in Early Life and Mental Health From Adolescence to Young Adulthood
Authors: Joanne B. Newbury, Jon Heron, James B. Kirkbride, Helen L. Fisher, Ioannis Bakolis, Andy Boyd, Richard Thomas, Stanley Zammit
Journal: JAMA Network Open (2024)

Importance Growing evidence associates air pollution exposure with various psychiatric disorders. However, the importance of early-life (eg, prenatal) air pollution exposure to mental health during youth is poorly understood, and few longitudinal studies have investigated the association of noise pollution with youth mental health. Objectives To examine the longitudinal associations of air and noise pollution exposure in pregnancy, childhood, and adolescence with psychotic experiences, depression, and anxiety in youths from ages 13 to 24 years. Design, Setting, and Participants This cohort study used data from the Avon Longitudinal Study of Parents and Children, an ongoing longitudinal birth cohort founded in 1991 through 1993 in Southwest England, United Kingdom. The cohort includes over 14 000 infants with due dates between April 1, 1991, and December 31, 1992, who were subsequently followed up into adulthood. Data were analyzed October 29, 2021, to March 11, 2024. Exposures A novel linkage (completed in 2020) was performed to link high-resolution (100 m 2 ) estimates of nitrogen dioxide (NO 2 ), fine particulate matter under 2.5 μm (PM 2.5 ), and noise pollution to home addresses from pregnancy to 12 years of age. Main outcomes and measures Psychotic experiences, depression, and anxiety were measured at ages 13, 18, and 24 years. Logistic regression models controlled for key individual-, family-, and area-level confounders. Results This cohort study included 9065 participants who had any mental health data, of whom (with sample size varying by parameter) 51.4% (4657 of 9051) were female, 19.5% (1544 of 7910) reported psychotic experiences, 11.4% (947 of 8344) reported depression, and 9.7% (811 of 8398) reported anxiety. Mean (SD) age at follow-up was 24.5 (0.8) years. After covariate adjustment, IQR increases (0.72 μg/m 3 ) in PM 2.5 levels during pregnancy (adjusted odds ratio [AOR], 1.11 [95% CI, 1.04-1.19]; P = .002) and during childhood (AOR, 1.09 [95% CI, 1.00-1.10]; P = .04) were associated with elevated odds for psychotic experiences. Pregnancy PM 2.5 exposure was also associated with depression (AOR, 1.10 [95% CI, 1.02-1.18]; P = .01). Higher noise pollution exposure in childhood (AOR, 1.19 [95% CI, 1.03-1.38]; P = .02) and adolescence (AOR, 1.22 [95% CI, 1.02-1.45]; P = .03) was associated with elevated odds for anxiety. Conclusions and Relevance In this longitudinal cohort study, early-life air and noise pollution exposure were prospectively associated with 3 common mental health problems from adolescence to young adulthood. There was a degree of specificity in terms of pollutant-timing-outcome associations. Interventions to reduce air and noise pollution exposure (eg, clean air zones) could potentially improve population mental health. Replication using quasi-experimental designs is now needed to shed further light on the underlying causes of these associations.
Reproductive isolation arises during laboratory adaptation to a novel hot environment
Authors: Sheng-Kai Hsu, Wei-Yun Lai, Johannes Novak, Felix Lehner, Ana Marija Jakšić, Elisabetta Versace, Christian Schlötterer
Journal: Genome biology (2024)

Abstract Background Reproductive isolation can result from adaptive processes (e.g., ecological speciation and mutation-order speciation) or stochastic processes such as “system drift” model. Ecological speciation predicts barriers to gene flow between populations from different environments, but not among replicate populations from the same environment. In contrast, reproductive isolation among populations independently adapted to the same/similar environment can arise from both mutation-order speciation or system drift. Results In experimentally evolved populations adapting to a hot environment for over 100 generations, we find evidence for pre- and postmating reproductive isolation. On one hand, an altered lipid metabolism and cuticular hydrocarbon composition pointed to possible premating barriers between the ancestral and replicate evolved populations. On the other hand, the pronounced gene expression differences in male reproductive genes may underlie the postmating isolation among replicate evolved populations adapting to the same environment with the same standing genetic variation. Conclusion Our study confirms that replicated evolution experiments provide valuable insights into the mechanisms of speciation. The rapid emergence of the premating reproductive isolation during temperature adaptation showcases incipient ecological speciation. The potential evidence of postmating reproductive isolation among replicates gave rise to two hypotheses: (1) mutation-order speciation through a common selection on early fecundity leading to an inherent inter-locus sexual conflict; (2) system drift with genetic drift along the neutral ridges.
TDR at 50: advancing a longstanding commitment to inclusion
Authors: John Reeder, Garry Aslanyan, Makiko Kitamura
Journal: BMJ (2024)

Fifty years after the formation of the Special Programme for Research and Training in Tropical Diseases, <b>John Reeder</b>, <b>Garry Aslanyan</b>, and <b>Makiko Kitamura</b> review their organisation's progress on advancing inclusive internationalism in health research
Spatiotemporal release of non-nucleotide STING agonist and AKT inhibitor from implantable 3D-printed scaffold for amplified cancer immunotherapy
Authors: Haixia Wang, Zheng Liu, Youqiang Fang, Xing Luo, Chunxiong Zheng, Yanteng Xu, Xiangfu Zhou, Qing Yuan, Shixian Lv, Limin Ma, Yeh-Hsing Lao, Yu Tao, Mingqiang Li
Journal: Biomaterials (2024)
The cardiac cycle modulates learning-related interoception
Authors: Miriam S. Nokia, Weiyong Xu, Jan Wikgren
Journal: Trends in Cognitive Sciences (2024)

Behavior is guided by the compatibility of expectations based on past experience and the outcome. In a recent study, Fouragnan and colleagues report that absolute prediction error (PE)-related heart-evoked potentials (HEPs) differ according to the cardiac cycle phase at outcome, and that the magnitude of this effect positively correlates with reward learning in healthy adults.
Toxicities associated with tyrosine kinase inhibitor maintenance following allogeneic hematopoietic cell transplantation in Philadelphia chromosome‐positive acute lymphoblastic leukemia
Authors: Tamer Othman, Paul Koller, Ni‐Chun Tsai, Dongyun Yang, Hoda Pourhassan, Vaibhav Agrawal, Dat Ngo, Jason Chen, Leonardo Farol, Ricardo Spielberger, Firoozeh Sahebi, Monzr M. Al Malki, Ji‐Lian Cai, Karamjeet S. Sandhu, Joshua Mansour, Amandeep Salhotra, Haris Ali, Ahmed Aribi, Shukaib Arslan, Guido Marcucci, Stephen J. Forman, Anthony S. Stein, Ryotaro Nakamura, Vinod Pullarkat, Ibrahim Aldoss, Matthew Mei
Journal: American Journal of Hematology (2024)

Abstract Allogeneic hematopoietic cell transplantation (HCT) offers a potential cure in Philadelphia chromosome‐positive (Ph+) acute lymphoblastic leukemia (ALL); nonetheless, relapses are common and the major cause of mortality. One strategy to prevent relapse is tyrosine kinase inhibitor (TKI) maintenance post‐HCT, but published clinical experience is primarily with the first‐generation TKI imatinib while data with newer generation TKIs are limited. We conducted a retrospective analysis of 185 Ph+ ALL patients who underwent HCT followed by TKI maintenance from 2003 to 2021 at City of Hope. Initially, 50 (27.0%) received imatinib, 118 (63.8%) received a second‐generation TKI (2G‐TKI), and 17 (9.2%) received ponatinib. A total of 77 patients (41.6%) required a dose reduction of their initial TKI due to toxicity. Sixty‐six patients (35.7%) did not complete maintenance due to toxicity; 69 patients (37.3%) discontinued 1 TKI, and 11 (5.9%) discontinued 2 TKIs due to toxicity. Initial imatinib versus 2G‐TKI versus ponatinib maintenance was discontinued in 19 (38.0%) versus 68 (57.6%) versus 3 (17.6%) patients due to toxicity ( p = .003), respectively. Patients on ponatinib as their initial TKI had a longer duration of TKI maintenance versus 2G‐TKI: 576.0 days (range, 72–921) versus 254.5 days (range, 3–2740; p = .02). The most common reasons for initial TKI discontinuation include gastrointestinal (GI) intolerance (15.1%), cytopenia (8.6%), and fluid retention (3.8%). The 5‐year overall survival and progression‐free survival for the total population were 78% and 71%, respectively. Our findings demonstrate the challenges of delivering post‐HCT TKI maintenance in a large real‐world cohort as toxicities leading to TKI interruptions, discontinuation, and dose reduction were common.
Utility of ultrasound in the diagnostic work-up of suspected pulmonary embolism: an open-label multicentre randomized controlled trial (the PRIME study)
Authors: Casper Falster, Mads Damgaard Mørkenborg, Mikkel Thrane, Jesper Clausen, Michael Arvig, Kristoffer Brockhattingen, Peter Biesenbach, Lasse Paludan, Rune Wiig Nielsen, Thi Anh Nhi Huynh, Mikael K. Poulsen, Mikkel Brabrand, Jacob E. Møller, Stefan Posth, Christian B. Laursen
Journal: The Lancet Regional Health - Europe (2024)

BackgroundPrevalence of pulmonary embolism (PE) in patients referred to diagnostic imaging is decreasing, indicating a need for improving patient selection. The aim of this study was to assess reduction in referral to diagnostic imaging by integrating a bespoke ultrasound protocol and describe associated failure rate and adverse events in patients with suspected PE.MethodsIn a randomized open-label multicentre trial spanning June 18, 2021, through Feb 1, 2023, adult patients with suspected PE and 1) a Wells score of 0–6 and elevated age-adjusted D-dimer or 2) Wells score >6 were randomly assigned 1:1 to direct diagnostic imaging (controls) or focused lung, cardiac, and deep venous ultrasound by unblinded investigators. Ultrasound could: 1) dismiss PE if no signs of PE and low clinical suspicion or an alternate diagnosis, 2) confirm PE in case of visible venous thrombus, ≥2 subpleural infarctions, McConnell's, or D-sign, or 3) refer to diagnostic imaging if neither category was fulfilled or a patient with confirmed PE by ultrasound required admission. Primary endpoint was proportion of patients referred to diagnostic imaging. Outcome assessors were not blinded to group assignment. All included participants were included in safety analyses. The trial was registered at clinicaltrials.gov (NCT04882579).FindingsA total of 150 patients were recruited, of whom 73 were randomized to ultrasound. Among 77 controls referred to diagnostic imaging, 26 patients had PE confirmed. In the ultrasound group, 40 patients were referred to diagnostic imaging of whom 20 had PE, reducing referral for diagnostic imaging by 45.2% (95% CI: 34.3–56.6, p < 0.0001). Three further PEs were diagnosed by presence of a DVT. During 3-month follow-up, the number of patients who did not receive anticoagulation but was diagnosed with PE was two (4%; 95% CI: 1.1–13.5) and none (0%; 95% CI: 0.0–7.0) in the ultrasound and control group, respectively.InterpretationUltrasound substantially reduced referral to diagnostic imaging in suspected PE. Albeit with an unacceptable failure rate.FundingUniversity of Southern Denmark, Odense University Hospital, Master Carpenter Sophus Jacobsen and wife's foundation, Engineer K. A. Rhode and wife foundation.
As needed ICS/formoterol: not all of Europe is equal
Authors: Andrew Bush, Winifried Randerath, Nicolas Roche
Journal: European Respiratory Journal (2024)

Inhaled corticosteroids (ICS) have revolutionised the treatment of those diseases characterised by eosinophilic airway inflammation, in particular asthma, but also eosinophilic phenotypes of COPD and bronchiectasis. These diseases affect large numbers of children and adults. However, persuading many patients to inhale ICS twice daily in an efficient manner has proved challenging. Typically, many if not most doses are omitted, and inhaler technique is poor, despite multiple teaching sessions. This means that for many people, asthma outcomes are suboptimal, and they are at risk of asthma attacks, which in some cases are fatal. Current licensing of single agent maintenance and reliever therapy ignores the evidence and has led to inequity across Europe <https://bit.ly/4d7j88U>
Plozasiran, an RNA Interference Agent Targeting APOC3, for Mixed Hyperlipidemia
Authors: Christie M. Ballantyne, Szilard Vasas, Masoud Azizad, Peter Clifton, Robert S. Rosenson, Ting Chang, Stacey Melquist, Rong Zhou, Ma’an Mushin, Nicholas J. Leeper, Jennifer Hellawell, Daniel Gaudet
Journal: New England Journal of Medicine (2024)

Persons with mixed hyperlipidemia are at risk for atherosclerotic cardiovascular disease due to an elevated non-high-density lipoprotein (HDL) cholesterol level, which is driven by remnant cholesterol in triglyceride-rich lipoproteins. The metabolism and clearance of triglyceride-rich lipoproteins are down-regulated through apolipoprotein C3 (APOC3)-mediated inhibition of lipoprotein lipase.
Circadian control of tumor immunosuppression affects efficacy of immune checkpoint blockade
Authors: Bridget M. Fortin, Shannon M. Pfeiffer, Jacob Insua-Rodríguez, Hamad Alshetaiwi, Alexander Moshensky, Wei A. Song, Alisa L. Mahieu, Sung Kook Chun, Amber N. Lewis, Alex Hsu, Isam Adam, Oliver S. Eng, Nicholas R. Pannunzio, Marcus M. Seldin, Ivan Marazzi, Francesco Marangoni, Devon A. Lawson, Kai Kessenbrock, Selma Masri
Journal: Nature Immunology (2024)
Cell-type-specific consequences of mosaic structural variants in hematopoietic stem and progenitor cells
Authors: Karen Grimes, Hyobin Jeong, Amanda Amoah, Nuo Xu, Julian Niemann, Benjamin Raeder, Patrick Hasenfeld, Catherine Stober, Tobias Rausch, Eva Benito, Johann-Christoph Jann, Daniel Nowak, Ramiz Emini, Markus Hoenicka, Andreas Liebold, Anthony Ho, Shimin Shuai, Hartmut Geiger, Ashley D. Sanders, Jan O. Korbel
Journal: Nature Genetics (2024)

The functional impact and cellular context of mosaic structural variants (mSVs) in normal tissues is understudied. Utilizing Strand-seq, we sequenced 1,133 single-cell genomes from 19 human donors of increasing age, and discovered the heterogeneous mSV landscapes of hematopoietic stem and progenitor cells. While mSVs are continuously acquired throughout life, expanded subclones in our cohort are confined to individuals >60. Cells already harboring mSVs are more likely to acquire additional somatic structural variants, including megabase-scale segmental aneuploidies. Capitalizing on comprehensive single-cell micrococcal nuclease digestion with sequencing reference data, we conducted high-resolution cell-typing for eight hematopoietic stem and progenitor cells. Clonally expanded mSVs disrupt normal cellular function by dysregulating diverse cellular pathways, and enriching for myeloid progenitors. Our findings underscore the contribution of mSVs to the cellular and molecular phenotypes associated with the aging hematopoietic system, and establish a foundation for deciphering the molecular links between mSVs, aging and disease susceptibility in normal tissues.
Noninvasive assessment of organ-specific and shared pathways in multi-organ fibrosis using T1 mapping
Authors: Victor Nauffal, Marcus D. R. Klarqvist, Matthew C. Hill, Danielle F. Pace, Paolo Di Achille, Seung Hoan Choi, Joel T. Rämö, James P. Pirruccello, Pulkit Singh, Shinwan Kany, Cody Hou, Kenney Ng, Anthony A. Philippakis, Puneet Batra, Steven A. Lubitz, Patrick T. Ellinor
Journal: Nature Medicine (2024)
Develop Targeted Protein Drug Carriers through a High‐Throughput Screening Platform and Rational Design
Authors: Xiaodan Li, Yanming Zuo, Xurong Lin, Binjie Guo, Haohan Jiang, Naiyu Guan, Hanyu Zheng, Yan Huang, Xiaosong Gu, Bin Yu, Xuhua Wang
Journal: Advanced Healthcare Materials (2024)

Protein-based drugs offer advantages, such as high specificity, low toxicity, and minimal side effects compared to small molecule drugs. However, delivery of proteins to target tissues or cells remains challenging due to the instability, diverse structures, charges, and molecular weights of proteins. Polymers have emerged as a leading choice for designing effective protein delivery systems, but identifying a suitable polymer for a given protein is complicated by the complexity of both proteins and polymers. To address this challenge, a fluorescence-based high-throughput screening platform called ProMatch to efficiently collect data on protein-polymer interactions, followed by in vivo and in vitro experiments with rational design is developed. Using this approach to streamline polymer selection for targeted protein delivery, candidate polymers from commercially available options are identified and a polyhexamethylene biguanide (PHMB)-based system for delivering proteins to white adipose tissue as a treatment for obesity is developed. A branched polyethylenimine (bPEI)-based system for neuron-specific protein delivery to stimulate optic nerve regeneration is also developed. The high-throughput screening methodology expedites identification of promising polymer candidates for tissue-specific protein delivery systems, thereby providing a platform to develop innovative protein-based therapeutics.