tbuckley/cabot-search huggingface dataset:
The convergent evolution of hummingbird pollination results in repeated floral scent loss through gene downregulation
Authors: Kathy Darragh, Kathleen M Kay, Santiago R Ramírez
Journal: Molecular Biology and Evolution (2025)

Abstract The repeated evolution of the same trait in different lineages provides powerful natural experiments to study the phenotypic and genotypic predictability of trait gain and loss. A fascinating example is the repeated evolution of hummingbird pollination in plant lineages in the Americas, a widespread and often unidirectional phenomenon. The spiral gingers in the genus Costus are ancestrally bee-pollinated, and hummingbird pollination has evolved multiple times independently in the tropical Americas. These pollinator transitions are accompanied by predictable morphological and color changes, but the changes in floral scent have not been described. In this study, we describe the floral scent composition of 30 species of Costus sampled across the phylogeny to understand how floral scent has evolved across the genus with respect to pollinator transitions. We then combine transcriptomics and genomics to identify genetic expression differences and gene family evolution associated with pollinator transitions. We show that hummingbird-pollinated species have mostly lost their floral scent, whereas bee-pollinated species exhibit either floral scent maintenance or in some cases, gains of more diverse scent profiles. We find the floral scent loss appears to be due to gene downregulation rather than pseudogenization. The remarkable consistency of scent loss in hummingbird-pollinated species highlights the shared strong selection pressures experienced by these lineages. Even species with more recent transitions from bee to hummingbird pollination exhibit scent loss, highlighting the rapid breakdown of scent emission following pollinator transitions. This research highlights the capacity for rapid changes when selection pressures are strong through downregulation of floral scent genes.
Extracorporeal Blood Purification in European Pediatric Intensive Care Units
Authors: Gabriella Bottari, Emanuele Buccione, Benan Bayrakci, George Briassoulis, Michael J. Carter, Demet Demirkol, Stavroula Ilia, Luc Morin, Karl Reiter, Maria-Jose Santiago, Luregn J. Schlapbach, Maria Slocker-Barrio, Pierre Tissieres, Tomás Zaoral, Stefania Bianzina, Akash Deep
Journal: JAMA Network Open (2025)

Importance Important advances have been made in extracorporeal blood purification therapies (EBPTs) due to new technologies and biomaterials; however, the lack of established guidelines is a factor in great variability in clinical practice. This aspect is accentuated in pediatric intensive care given the small number of patients with diverse diagnoses treated with EBPT and the technical challenges in treating small children, potentiating the risk of adverse events. Objective To understand what experienced users of EBPT think about its relevant issues, insight that may have implications for the design of future studies, and the application of EBPTs in patient care. Evidence Review Literature search was conducted using the PubMed and Embase databases between January 1, 2020, and July 15, 2024, and a combination of key medical terms. A panel of experts was formed (composed of 15 authors and pediatric intensivists) to develop a consensus statement using a modified Delphi-based model between 2022 and 2024. The panel’s core team drafted the initial questionnaire, which explored EBPT use in pediatric intensive care units (PICUs), including clinical indications for initiating and discontinuing use and outcomes for assessing effectiveness and safety. SurveyMonkey was used in the distribution, completion, and revision of the questionnaire, and findings were analyzed. Panelists were asked to rank answer choices. Numerical value for each ranking was translated to a percentage defining the strength of consensus (&amp;amp;gt;90% agreement from panelists signifying strong consensus; &amp;amp;lt;49% signifying no consensus). Findings A total of 116 survey responses were received from panelists from 8 European countries. Strong consensus was achieved on 6 of 24 questions and consensus (75%-90% agreement) was reached on 18 of 24 questions. According to the panelists, the continuous renal replacement therapy standard or enhanced adsorption hemofilter and plasma exchange were of interest, representing the most applied EBPTs across various applications. While evidence on hemoadsorption is growing, it remains limited. Conclusions and Relevance This consensus statement on EBPTs in critically ill pediatric patients was developed by an international panel of experts in areas where clinical evidence is still limited. This consensus statement could support pediatric intensivists in bedside decision-making and guide future research on EBPTs in PICUs.
Individual and additive effects of vitamin D, omega-3 and exercise on DNA methylation clocks of biological aging in older adults from the DO-HEALTH trial
Authors: Heike A. Bischoff-Ferrari, Stephanie Gängler, Maud Wieczorek, Daniel W. Belsky, Joanne Ryan, Reto W. Kressig, Hannes B. Stähelin, Robert Theiler, Bess Dawson-Hughes, René Rizzoli, Bruno Vellas, Laure Rouch, Sophie Guyonnet, Andreas Egli, E. John Orav, Walter Willett, Steve Horvath
Journal: Nature Aging (2025)

Abstract While observational studies and small pilot trials suggest that vitamin D, omega-3 and exercise may slow biological aging, larger clinical trials testing these treatments individually or in combination are lacking. Here, we report the results of a post hoc analysis among 777 participants of the DO-HEALTH trial on the effect of vitamin D (2,000 IU per day) and/or omega-3 (1 g per day) and/or a home exercise program on four next-generation DNA methylation (DNAm) measures of biological aging (PhenoAge, GrimAge, GrimAge2 and DunedinPACE) over 3 years. Omega-3 alone slowed the DNAm clocks PhenoAge, GrimAge2 and DunedinPACE, and all three treatments had additive benefits on PhenoAge. Overall, from baseline to year 3, standardized effects ranged from 0.16 to 0.32 units (2.9–3.8 months). In summary, our trial indicates a small protective effect of omega-3 treatment on slowing biological aging over 3 years across several clocks, with an additive protective effect of omega-3, vitamin D and exercise based on PhenoAge.
Genotype-Based Molecular Mechanisms in Alport Syndrome
Authors: Emine Bilge Caparali, Vanessa De Gregorio, Moumita Barua
Journal: Journal of the American Society of Nephrology (2025)

Abstract Alport syndrome (AS) is an inherited disorder characterized by kidney disease, sensorineural hearing loss and ocular abnormalities. AS is caused by pathogenic variants in COL4A3 , COL4A4 or COL4A5 , which encode the α3, α4 and α5 chains of type IV collagen that forms a heterotrimer expressed in the glomerular basement membrane. Knowledge of its genetic basis has informed the development of different models in dogs, mice and rat that reflect its autosomal and X-linked inheritance patterns as well as different mutation types, including protein truncating and missense variants. A key difference between these two types is the synthesis of α3α4α5(IV), which is not made in autosomal AS (2 pathogenic variants in trans or biallelic) or males with X-linked Alport syndrome due to protein truncating variants. By contrast, α3α4α5(IV) is synthesized in AS due to missense variants. For missense variants, in vitro studies suggest that these cause impaired type IV collagen trafficking and ER stress. For protein truncating variants, knockout models suggest that persistence of an immature α1α1α2(IV) network is associated with biomechanical strain, which activates endothelin-A receptors leading to mesangial filopodia formation. Moreoever, studies suggest that activation of collagen receptors integrins and DDR1 play a role in disease propagation. In this review, we provide an overview of how these genotype-phenotype-mechanisms are key for a precision medicine-based approach in the future.
Availability, cost and affordability of essential medicines for smoking cessation in low-income and middle-income countries: a cross-sectional study
Authors: Catherine Plum, Marie Stolbrink, Obianuju Ozoh, Shamanthi Jayasooriya, Rebecca Nightingale, Kevin Mortimer, David Halpin
Journal: Thorax (2025)

Smoking cessation is more effective when supported by medicines. Data on the availability, cost and affordability of these treatments in low-income and middle-income countries (LMIC) are limited. Cross-sectional data for smoking cessation medications were collected from pharmacies, healthcare facilities and central medicine stores in 60 LMIC (2022-2023). Medications had varying availability, large price ranges and were essentially unaffordable. Enabling access to these medications is important in reducing tobacco consumption and associated disease. Strategies for integrating smoking cessation services into health systems are needed to reach Sustainable Development Goal targets.
Short-Term Metformin Protects Against Glucocorticoid-Induced Toxicity in Healthy Subjects: A Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Susanne Thierry, Caspar Joyce Peterson, Stéphanie Pfammatter, Patricia Arroyo Tardio, Christian Meier, Tarik Delko, Vasco Iten, Christine S. Zuern, Michael Kühne, Michael Epstein, Alaa Othman, Nicola Zamboni, Isabel Reinisch, Adhideb Ghosh, Christian Wolfrum, Eleonora Seelig
Journal: Diabetes Care (2025)

OBJECTIVE Glucocorticoids (GCs) are potent anti-inflammatory drugs, but strategies to prevent side effects are lacking. We investigated whether metformin could prevent GC-related toxicity and explored the underlying mechanisms. RESEARCH DESIGN AND METHODS This single-center, randomized, placebo-controlled, double-blind, crossover trial compared metformin with placebo during high-dose GC treatment in 18 lean, healthy, male study participants. The trial was conducted at the University Hospital Basel, Switzerland. Participants received prednisone 30 mg/d in combination with metformin or placebo for two 7-day periods (1:1 randomization). The primary outcome, change in insulin sensitivity, was assessed using a two-sided paired t test. Before and after each study period, we conducted a mixed-meal tolerance test, blood metabolomics, and RNA sequencing of subcutaneous adipose tissue biopsy specimens. RESULTS Metformin improved insulin sensitivity as assessed by the Matsuda index (n = 17; mean change: −2.73 ± 3.55 SD for placebo, 2.21 ± 3.95 for metformin; mean difference of change −4.94 [95% CI, −7.24, −2.65)]; P &amp;lt; 0.001). Metabolomic and transcriptomic analyses revealed that metformin altered fatty acid flux in the blood and downregulated genes involved in fatty acid synthesis in adipose tissue. Metformin reduced markers of protein breakdown and bone resorption. Furthermore, metformin downregulated genes responsible for AMPK inhibition and affected GLP1 and bile acid metabolism. CONCLUSIONS Metformin prevents GC-induced insulin resistance and reduces markers of dyslipidemia, myopathy, and, possibly, bone resorption through AMPK-dependent and -independent pathways.
The effect of prenatal balanced energy and protein supplementation on gestational weight gain: An individual participant data meta-analysis in low- and middle-income countries
Authors: Dongqing Wang, Uttara Partap, Enju Liu, Janaína Calu Costa, Ilana R. Cliffer, Molin Wang, Sudeer Kumar Nookala, Vishak Subramoney, Brittany Briggs, Imran Ahmed, Alemayehu Argaw, Shabina Ariff, Nita Bhandari, Ranadip Chowdhury, Daniel Erchick, Armando García-Guerra, Masoumah Ghaffarpour, Giles Hanley-Cook, Lieven Huybregts, Fyezah Jehan, Fatemeh Kaseb, Nancy F. Krebs, Carl Lachat, Tsering Pema Lama, Dharma S. Manandhar, Elizabeth M. McClure, Sophie E. Moore, Ameer Muhammad, Lynnette M. Neufeld, Andrew M. Prentice, Amado D. Quezada-Sánchez, Dominique Roberfroid, Naomi M. Saville, Yasir Shafiq, Bhim P. Shrestha, Bakary Sonko, Sajid Soofi, Sunita Taneja, James M. Tielsch, Laéticia Céline Toe, Naser Valaei, Wafaie W. Fawzi
Journal: PLoS Medicine (2025)

Understanding the effects of balanced energy and protein (BEP) supplements on gestational weight gain (GWG) and how the effects differ depending on maternal characteristics and the nutritional composition of the supplements will inform the implementation of prenatal BEP interventions. Individual participant data from 11 randomized controlled trials of prenatal BEP supplements (N = 12,549, with 5,693 in the BEP arm and 6,856 in the comparison arm) in low- and middle-income countries were used. The primary outcomes included GWG adequacy (%) and the estimated total GWG at delivery as continuous outcomes, and severely inadequate (<70% adequacy), inadequate GWG (<90% adequacy), and excessive GWG (>125% adequacy) as binary outcomes; all variables were calculated based on the Institute of Medicine recommendations. Linear and log-binomial models were used to estimate study-specific mean differences or risk ratios (RRs), respectively, with 95% confidence intervals (CIs) of the effects of prenatal BEP on the GWG outcomes. The study-specific estimates were pooled using meta-analyses. Subgroup analyses were conducted by individual characteristics. Subgroup analyses and meta-regression were conducted for study-level characteristics. Compared to the comparison group, prenatal BEP led to a 6% greater GWG percent adequacy (95% CI: 2.18, 9.56; p = 0.002), a 0.59 kg greater estimated total GWG at delivery (95% CI, 0.12, 1.05; p = 0.014), a 10% lower risk of severely inadequate GWG (RR: 0.90; 95% CI: 0.83, 0.99; p = 0.025), and a 7% lower risk of inadequate GWG (RR: 0.93; 95% CI: 0.89, 0.97; p = 0.001). The effects of prenatal BEP on GWG outcomes were stronger in studies with a targeted approach, where BEP supplements were provided to participants in the intervention arm under specific criteria such as low body mass index or low GWG, compared to studies with an untargeted approach, where BEP supplements were provided to all participants allocated to the intervention arm. Prenatal BEP supplements are effective in increasing GWG and reducing the risk of inadequate weight gain during pregnancy. BEP supplementation targeted toward pregnant women with undernutrition may be a promising approach to delivering the supplements.
Author Correction: Genetically adjusted PSA levels for prostate cancer screening
Authors: Linda Kachuri, Thomas J. Hoffmann, Yu Jiang, Sonja I. Berndt, John P. Shelley, Kerry R. Schaffer, Mitchell J. Machiela, Neal D. Freedman, Wen-Yi Huang, Shengchao A. Li, Ryder Easterlin, Phyllis J. Goodman, Cathee Till, Ian Thompson, Hans Lilja, Stephen K. Van Den Eeden, Stephen J. Chanock, Christopher A. Haiman, David V. Conti, Robert J. Klein, Jonathan D. Mosley, Rebecca E. Graff, John S. Witte
Journal: Nature Medicine (2025)
IL-10 from tumoral B cells modulates the diffuse large B-cell lymphoma microenvironment and response to immunotherapy
Authors: Marcos Garcia-Lacarte, Sara C Grijalba, Javier Melchor Sánchez, Marien Pascual, Enrique Goni, Inigo Clemente-Larramendi, Sandra Morales-Sanchez, Maria A Burrell, Oscar Blanco, Adrian Arnaiz-Leché, Blanca S Berrozpe, Maria Amann, Christian Klein, Pablo Umaña, Miguel Angel Canales, Jose Angel Martinez-Climent, Juan Jose Lasarte, Pablo Sarobe, Francisco J Novo, Sergio Roa
Journal: Blood (2025)
Deficiency of T follicular helper cell Tet3 DNA demethylation inhibits pathogenic IgG2c class switching and chronic GVHD
Authors: Michael C. Zaiken, Sujeong Jin, Cameron McDonald-Hyman, Christina Hartigan, Peter Sage, Keli L. Hippen, Brent H Koehn, Angela Panoskaltsis-Mortari, Megan J Riddle, Cindy Eide, Jakub Tolar, Geoffrey R Hill, Leo Luznik, Corey S. Cutler, Jerome Ritz, Leslie S Kean, Ageliki Tsagaratou, Anjana Rao, Bruce R Blazar
Journal: Blood (2025)
Prevention of Episodic Migraine Headache Using Pharmacologic Treatments in Outpatient Settings: A Clinical Guideline From the American College of Physicians
Authors: Amir Qaseem, Thomas G. Cooney, Itziar Etxeandia-Ikobaltzeta, Timothy J. Wilt, Curtis S. Harrod, Jeffrey A. Tice, Carolyn J. Crandall, Lauri A. Hicks, J. Thomas Cross, Nick Fitterman, Johanna Lewis, Amy M. Linsky, Michael Maroto, Matthew C. Miller, Adam J. Obley, Douglas K. Owens, Paul G. Shekelle, Tatyana Shamliyan, Jennifer Yost
Journal: Annals of Internal Medicine (2025)

The American College of Physicians (ACP) developed this clinical guideline for clinicians caring for adults with episodic migraine headache (defined as 1 to 14 headache days per month) in outpatient settings. ACP based these recommendations on systematic reviews of the comparative benefits and harms of pharmacologic treatments to prevent episodic migraine, patients' values and preferences, and economic evidence. ACP evaluated the comparative effectiveness of the following interventions: angiotensin-converting enzyme inhibitors (lisinopril), angiotensin II-receptor blockers (candesartan and telmisartan), antiseizure medications (valproate and topiramate), β-blockers (metoprolol and propranolol), calcitonin gene-related peptide (CGRP) antagonist-gepants (atogepant or rimegepant), CGRP monoclonal antibodies (eptinezumab, erenumab, fremanezumab, or galcanezumab), selective serotonin reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors (fluoxetine and venlafaxine), and a tricyclic antidepressant (amitriptyline). ACP used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to analyze the effects of pharmacologic treatment on the following outcomes: migraine frequency and duration, number of days medication was taken for acute treatment of migraine, frequency of migraine-related emergency department visits, migraine-related disability, quality of life and physical functioning, and discontinuations due to adverse events. In addition, adverse events were captured through U.S. Food and Drug Administration medication labels and eligible studies. In this guideline, ACP makes recommendations for clinicians to initiate monotherapy for episodic migraine prevention in nonpregnant adults in the outpatient setting as well as alternative approaches if initial treatments are not tolerated or result in an inadequate response. All 3 ACP recommendations have conditional strength and low-certainty evidence. Clinical considerations provide additional context for physicians and other clinicians.
Comparative Effectiveness of Pharmacologic Treatments for the Prevention of Episodic Migraine Headache: A Systematic Review and Network Meta-analysis for the American College of Physicians
Authors: Johanna A.A. Damen, Bada Yang, Demy L. Idema, Robin W.M. Vernooij, Linde Huis in ‘t Veld, Mike Kusters, Rene Spijker, Kim van der Braak, Pauline Heus, Kevin Jenniskens, Lotty Hooft
Journal: Annals of Internal Medicine (2025)

Various treatments for preventing episodic migraine are available. To evaluate the comparative effectiveness and harms of pharmacologic prevention of episodic migraine, focusing on treatments already determined to be superior to placebo. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from inception until April 2024. Randomized trials evaluating selected efficacious pharmacologic treatments in adults with episodic migraine. Selection was done independently by 2 reviewers. Data were extracted by 1 reviewer and checked by a second. Risk of bias and certainty of the evidence were assessed using the Cochrane Risk of Bias tool and the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach, respectively. Sixty-one studies (20 680 patients) evaluating 16 treatments were included. Nineteen studies had low risk of bias. All selected treatments were deemed efficacious against placebo on the basis of previous systematic reviews. In network meta-analyses, calcitonin gene-related peptide antagonist monoclonal antibodies (CGRP-mAbs) probably resulted in fewer discontinuations due to adverse events than topiramate (risk difference, -16.2% [95% CI, -18.4% to -12.8%]; moderate-certainty evidence), and CGRP-mAbs may result in less migraine-related disability and improved quality of life compared with gepants (mean differences, -4.12 [CI, -9.30 to 1.05] and 2.25 [CI, -0.85 to 5.34], respectively; low-certainty evidence). For other outcomes and comparisons, there was moderate- or low-certainty evidence of no clinically important differences, uncertain evidence, or no evidence. Limited literature was available to determine the minimal important differences. The number of head-to-head comparisons of treatments was limited. No high-certainty evidence favored one pharmacologic treatment for prevention of episodic migraine over another. Evidence was mostly insufficient or of low certainty. American College of Physicians. (PROSPERO: CRD42023414305).
Pharmacologic Treatment of Primary Osteoporosis or Low Bone Mass to Prevent Fractures in Adults: A Living Clinical Guideline From the American College of Physicians (Version 1: Update Alert 1: Surveillance Note 1)
Authors: Amir Qaseem, Thomas G. Cooney, Tatyana A. Shamliyan, Jennifer Yost, Lauri A. Hicks, Lauri A. Hicks, Ethan M. Balk, Ethan M. Balk, Thomas G. Cooney, J. Thomas Cross, J. Thomas Cross, Nick Fitterman, Nick Fitterman, Johanna Lewis, Johanna Lewis, Amy M. Linsky, Amy M. Linsky, Michael Maroto, Michael Maroto, Matthew C. Miller, Matthew C. Miller, Adam J. Obley, Adam J. Obley, Douglas K. Owens, Douglas K. Owens, Paul G. Shekelle, Paul G. Shekelle, Jeffrey. A. Tice, Jeffrey. A. Tice, Itziar Etxeandia-Ikobaltzeta, Itziar Etxeandia-Ikobaltzeta, Amir Qaseem, Tatyana A. Shamliyan, Jennifer Yost
Journal: Annals of Internal Medicine (2025)
In acute ischemic stroke with AF, early DOAC initiation was noninferior to delayed initiation for ischemic and hemorrhagic outcomes at 90 d
Authors: Mukul Sharma, Abhilekh Srivastava
Journal: Annals of Internal Medicine (2025)

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Emerging roles of extracellular vesicles in oral and maxillofacial areas
Authors: Qianting Wang, Jiayu Sun, Haci Jiang, Mengfei Yu
Journal: International Journal of Oral Science (2025)

Abstract The oral and maxillofacial region is a highly complex area composed of multiple tissue types and bears various critical functions of the human body. Diseases in this region pose significant diagnostic and management challenges; therefore, exploring new strategies for early diagnosis, targeted treatment, and tissue reconstruction is key to improving patient prognosis and quality of life. Extracellular vesicles are a group of heterogeneous lipid-bilayer membrane structures secreted by most cell types, including exosomes, microvesicles, and apoptotic bodies. Present in various body fluids and tissues, they act as messengers via the transfer of nucleic acids, proteins, and metabolites to recipient cells. To date, studies have revealed the different roles of extracellular vesicles in physiological or pathological processes, as well as applications in disease diagnosis, prognosis, and treatment. The importance and tissue specificity of the dental and maxillofacial tissues indicate that extracellular vesicles derived from this region are promising for further research. This paper reviews the published data on extracellular vesicles derived from cells, body fluids, and tissues in oral and maxillofacial regions, summarizes the latest advances in extracellular vesicles from extensive sources, and concludes with a focus on the current research progress and application prospects of engineered exosomes in oral science.