tbuckley/cabot-search huggingface dataset:
Diversity and molecular evolution of non-visual opsin genes across environmental, developmental, and morphological adaptations in frogs
Authors: John L Boyette, Rayna C Bell, Matthew K Fujita, Kate N Thomas, Jeffrey W Streicher, David J Gower, Ryan K Schott
Journal: Molecular Biology and Evolution (2024)

Nonvisual opsins are transmembrane proteins expressed in the eyes and other tissues of many animals. When paired with a light-sensitive chromophore, nonvisual opsins form photopigments involved in various nonvisual, light-detection functions including circadian rhythm regulation, light-seeking behaviors, and seasonal responses. Here, we investigate the molecular evolution of nonvisual opsin genes in anuran amphibians (frogs and toads). We test several evolutionary hypotheses including the predicted loss of nonvisual opsins due to nocturnal ancestry and potential functional differences in nonvisual opsins resulting from environmental light variation across diverse anuran ecologies. Using whole-eye transcriptomes of 81 species, combined with genomes, multitissue transcriptomes, and independently annotated genes from an additional 21 species, we identify which nonvisual opsins are present in anuran genomes and those that are also expressed in the eyes, compare selective constraint among genes, and test for potential adaptive evolution by comparing selection between discrete ecological classes. At the genomic level, we recovered all 18 ancestral vertebrate nonvisual opsins, indicating that anurans demonstrate the lowest documented amount of opsin gene loss among ancestrally nocturnal tetrapods. We consistently found expression of 14 nonvisual opsins in anuran eyes and detected positive selection in a subset of these genes. We also found shifts in selective constraint acting on nonvisual opsins in frogs with differing activity periods, habitats, distributions, life histories, and pupil shapes, which may reflect functional adaptation. Although many nonvisual opsins remain poorly understood, these findings provide insight into the diversity and evolution of these genes across anurans, filling an important gap in our understanding of vertebrate opsins and setting the stage for future research on their functional evolution across taxa.
MiTES: itch or pain?
Authors: Cristina Has
Journal: British Journal of Dermatology (2024)

Journal Article Accepted manuscript MiTES: itch or pain Get access Cristina Has Cristina Has Department of Dermatology, Medical Center University of Freiburg, Germany Corresponding Author: Email:cristina.has@uniklinik-freiburg.de https://orcid.org/0000-0001-6066-507X Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljae198, https://doi.org/10.1093/bjd/ljae198 Published: 13 May 2024 Article history Received: 28 April 2024 Accepted: 09 May 2024 Published: 13 May 2024
Diagnostic accuracy of autofluorescence-Raman microspectroscopy for surgical margin assessment during Mohs micrographic surgery of basal cell carcinoma
Authors: Radu A Boitor, Sandeep Varma, Ashish Sharma, Sunita Odedra, Somaia Elsheikh, Karim Eldib, Anand Patel, Alexey Koloydenko, Sonia Gran, Koen De Winne, Senada Koljenovic, Hywel C Williams, Ioan Notingher
Journal: British Journal of Dermatology (2024)

Abstract Background Autofluorescence (AF)–Raman microspectroscopy is a technology that can detect residual basal cell carcinoma (BCC) on the resection margin of fresh, surgically excised tissue specimens. The technology does not require tissue fixation, staining, labelling or sectioning, and provides quantitative diagnosis maps of the surgical margins in 30 min. Objectives To determine the accuracy of the AF–Raman instrument in detecting incomplete BCC excisions during Mohs micrographic surgery (MMS), using histology as the reference standard. Methods Skin layers from 130 patients undergoing MMS at the Nottingham University Hospitals NHS Trust (September 2022–July 2023) were investigated with the AF–Raman instrument. The layers were measured when fresh, immediately after excision. The AF–Raman results and the intraoperative assessment by Mohs surgeons were compared with a postoperative consensus-derived reference produced by three dermatopathologists. The sensitivity, specificity, and positive and negative predictive values were calculated. The study was registered with ClinicalTrials.gov (NCT03482622). Results AF–Raman analysis was successfully completed for 125 of 130 layers and, on average, covered 91% of the specimen surface area, with the lowest surface area covered being 87% for the eyelid and the highest being 94% for forehead specimens. The AF–Raman instrument identified positive margins in 24 of 36 BCC-positive cases [67% sensitivity, 95% confidence interval (CI) 49–82] and negative margins in 65 of 89 BCC-negative cases (73% specificity, 95% CI 63–82). Only one of 12 false-negative cases was caused by misclassification by the AF–Raman algorithm. The other 11 false-negatives cases were a result of no valid Raman signal being recorded at the location of the residual BCC due to either occlusion by blood or poor contact between tissue and the cassette window. The intraoperative diagnosis by Mohs surgeons identified positive margins in 31 of 36 BCC-positive cases (86% sensitivity, 95% CI 70–95) and negative margins in 79 of 89 BCC-negative cases (89% specificity, 95% CI 81–95). Conclusions The AF–Raman instrument has the potential to provide intraoperative microscopic assessment of surgical margins in BCC surgery. Further improvements are required for tissue processing, to ensure complete coverage of the surgical specimens.
Sixty Years of Hemodynamic Pharmacology in Obstructive Hypertrophic Cardiomyopathy
Authors: Steve R Ommen
Journal: New England Journal of Medicine (2024)

In April 1964, leading cardiologists, cardiovascular surgeons, and pathologists convened in London for a 2-day symposium to discuss a relatively new disease entity that we now know as obstructive hypertrophic cardiomyopathy (HCM).1 The proceedings kicked off with a comment by the group's chairman: "I have never before taken part in a discussion in which we start with so few fixed or preconceived ideas. We are in fact launching into poorly charted seas and perhaps we shall end the discussions with a slightly better map."2 Notable discussions included the results from invasive hemodynamic studies that had been carried out between 1960 . . .
Blood RNA-sequencing across the continuum of ANA-positive autoimmunity reveals insights into initiating immunopathology
Authors: Lucy Marie Carter, Md Yuzaiful Md Yusof, Zoe Wigston, Darren Plant, Stephanie Wenlock, Adewonuola Alase, Antonios Psarras, Edward M Vital
Journal: Annals of the Rheumatic Diseases (2024)

Mechanisms underpinning clinical evolution to systemic lupus erythematosus (SLE) from preceding antinuclear antibodies (ANA) positivity are poorly understood. This study aimed to understand blood immune cell transcriptional signatures associated with subclinical ANA positivity, and progression or non-progression to SLE.
Staged Bilateral MRI-Guided Focused Ultrasound Subthalamotomy for Parkinson Disease
Authors: Raúl Martínez-Fernández, Elena Natera-Villalba, Rafael Rodríguez-Rojas, Marta del Álamo, Jose A. Pineda-Pardo, Ignacio Obeso, Pasqualina Guida, Tamara Jiménez-Castellanos, Diana Pérez-Bueno, Alicia Duque, Jorge U. Mañez-Miró, Carmen Gasca-Salas, Michele Matarazzo, Fernando Alonso-Frech, Jose A. Obeso
Journal: JAMA Neurology (2024)

Unilateral magnetic resonance imaging (MRI)-guided focused ultrasound subthalamotomy (FUS-STN) improves cardinal motor features among patients with asymmetrical Parkinson disease (PD). The feasibility of bilateral FUS-STN is as yet unexplored.
The determinants of proxy treadmilling in evolutionary models of reliable signals
Authors: Keith D. Harris
Journal: Behavioral and Brain Sciences (2024)

Abstract Identifying the conditions of proxy treadmilling is crucial for determining whether reliable signals can persist over time. I present a framework that maps evolutionary models of reliable signals according to their assumptions regarding the effects of Goodhart's law. This framework can explain the contrasting outcomes of different modelling approaches, and identify in which models proxy treadmilling is expected to occur.
Proxy failure in academia: More than just another example
Authors: Milind Watve
Journal: Behavioral and Brain Sciences (2024)

Abstract Proxy failure in academia has progressed much ahead of what John et al. describe. We see advanced phenomena such as proxy complimentarity in which different players push each others' proxy failures; proxy exploitation in which external agents exploit players' proxies and predatory proxies that devour the goal itself. Academics need to avoid proxy failures by designing behaviorally sound systems.
Subjective and objective corruption of intuition and rational choice
Authors: David Haig
Journal: Behavioral and Brain Sciences (2024)

Abstract A societal shift has occurred toward making impactful decisions on the basis of objective metrics rather than subjective impressions. This shift is commonly justified by claims that we should not trust subjective intuitions. These are often unjust and thereby corrupt. However, the proxies used to make objective decisions are subject to a different form of corruption, characterized as proxy failure.
Reductionism and proxy failure: From neuroscience to target-based drug discovery
Authors: Arash Sadri, Sepideh Paknezhad
Journal: Behavioral and Brain Sciences (2024)

Abstract Reductionist methodologies reduce phenomena to some of their lower-level components. Researchers gradually shift their focus away from observing the actual object of study toward investigating and optimizing such lower-level proxies. Following reductionism, these proxies progressively diverge further from the original object of study. We vividly illustrate this in the evolution of target-based drug discovery from rational and phenotypic drug discovery.
Gold core@CeO2 halfshell Janus nanocomposites catalyze targeted sulfate radical for periodontitis therapy
Authors: Sijia Li, Qihang Ding, Lingling Zhang, Fangyu Shi, Chengyu Liu, Tingxuan Li, Yujia Shi, Manlin Qi, Lin Wang, Biao Dong, Shuyan Song, Jiao Sun, Jong Seung Kim, Chunyan Li
Journal: Journal of Controlled Release (2024)
Primary Care’s Role in Prescribing Mail-Order Mifepristone
Authors: Emily M. Godfrey, Ying Zhang, Debra B. Stulberg
Journal: JAMA Internal Medicine (2024)

This Viewpoint discusses the controversy over mail-order mifepristone prescribed by primary care clinicians for first-trimester abortion as it relates to the history of initial approval, the Supreme Court case Alliance for Hippocratic Medicine v US Food and Drug Administration, and available clinical research.
Hollow microneedles for ocular drug delivery
Authors: Shilpkala Gade, Katie Glover, Deepakkumar Mishra, Sanjiv Sharma, Owen Guy, Ryan F. Donnelly, Lalitkumar K. Vora, Raghu Raj Singh Thakur
Journal: Journal of Controlled Release (2024)

Microneedles (MNs) are micron-sized needles, typically <2 mm in length, arranged either as an array or as single needle. These MNs offer a minimally invasive approach to ocular drug delivery due to their micron size (reducing tissue damage compared to that of hypodermic needles) and overcoming significant barriers in drug administration. While various types of MNs have been extensively researched, significant progress has been made in the use of hollow MNs (HMNs) for ocular drug delivery, specifically through suprachoroidal injections. The suprachoroidal space, situated between the sclera and choroid, has been targeted using optical coherence tomography-guided injections of HMNs for the treatment of uveitis. Unlike other MNs, HMNs can deliver larger volumes of formulations to the eye. This review primarily focuses on the use of HMNs in ocular drug delivery and explores their ocular anatomy and the distribution of formulations following potential HMN administration routes. Additionally, this review focuses on the influence of formulation characteristics (e.g., solution viscosity, particle size), HMN properties (e.g., bore or lumen diameter, MN length), and routes of administration (e.g., periocular transscleral, suprachoroidal, intravitreal) on the ocular distribution of drugs. Overall, this paper highlights the distinctive properties of HMNs, which make them a promising technology for improving drug delivery efficiency, precision, and patient outcomes in the treatment of ocular diseases.
On abstract goals’ perverse effects on proxies: The dynamics of unattainability
Authors: José-Miguel Fernández-Dols
Journal: Behavioral and Brain Sciences (2024)

Abstract Proxies should not be classified as failures or successes because, in most cases, they are impossible translations of abstract, polysemous goals to supposedly univocal concrete measures. The “success” or “failure” of a proxy does not depend on its actual accuracy as a valid indicator of goal attainment, but on a social system's willingness to maintain an illusion of its accomplishment.
Proxy failures in practice: Examples from the sociology of science
Authors: Jakob Kapeller, Stephan Pühringer, Johanna Rath, Matthias Aistleitner
Journal: Behavioral and Brain Sciences (2024)

Abstract Following John et al., we provide examples of failing proxies that might help to contextualize the role of proxy failures in applied research. We focus on examples from the sociology of science and illustrate how the notion of proxy failure can sharpen applied analysis, if used in a way that does not obscure other dysfunctional effects of proxies.
Corrigendum to “Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of ANCA–Associated Vasculitis.” Kidney International 2024;105(3):447–449
Authors: Jürgen Floege, David R.W. Jayne, Jan-Stephan F. Sanders, Vladimír Tesar, Ethan M. Balk, Craig E. Gordon, Gaelen Adam, Marcello A. Tonelli, Michael Cheung, Amy Earley, Brad H. Rovin
Journal: Kidney International (2024)
“You’re free from just a girl or a boy”: Nonbinary children’s understanding of their gender
Authors: Fernando Salinas-Quiroz, Tuğçe Aral, Jessie Hillekens, Sophie Hölscher, Jocelyn Demos
Journal: International Journal of Transgender Health (2024)

Background In recent years, research on gender diversity in early childhood has increased significantly. However, much of the published literature still focuses on children whose experiences align with binary gender norms, inadvertently excluding nonbinary experiences from analysis.
Semaglutide and NT-proBNP in Obesity-Related HFpEF
Authors: Mark C. Petrie, Barry A. Borlaug, Javed Butler, Melanie J. Davies, Dalane W. Kitzman, Sanjiv J. Shah, Subodh Verma, Thomas Jon Jensen, Mette Nygaard Einfeldt, Karoline Liisberg, Eduardo Perna, Kavita Sharma, Justin A. Ezekowitz, Michael Fu, Vojtěch Melenovský, Hiroshi Ito, Małgorzata Lelonek, Mikhail N. Kosiborod
Journal: Journal of the American College of Cardiology (2024)

The glucagon-like peptide-1 receptor agonist, semaglutide, improved health status and reduced body weight in patients with obesity-related heart failure (HF) with preserved ejection fraction (HFpEF) in the STEP-HFpEF Program. Whether benefits were due to mechanical unloading or effects on HF pathobiology is uncertain. Determine if semaglutide 2.4 mg reduced N-terminal pro-brain natriuretic peptide (NTproBNP) in patients with obesity-related HFpEF and compare treatment responses by baseline NTproBNP. Prespecified secondary analysis of pooled data from two double-blind, placebo-controlled, randomized trials (STEP-HFpEF and STEP-HFpEF DM) testing effects of semaglutide in patients with obesity-related HFpEF. The main outcomes were change in NTproBNP at 52 weeks and change in the dual primary endpoints of KCCQ-CSS and body weight by baseline NTproBNP. 1145 patients were randomized. Semaglutide, compared with placebo, reduced NTproBNP at 52 weeks (estimated treatment ratio 0.82 [95% CI: 0.74-; 0.91]; P = 0.0002). Improvements in health status were more pronounced in those with higher vs lower baseline NTproBNP (estimated difference: tertile 1: 4.5 points [95% CI: 0.8–8.2], tertile 2: 6.2 points [95% CI: 2.4–10.0], tertile 3: 11.9 points [95% CI: 8.1–15.7]; interaction P = 0.02; baseline NTproBNP as a continuous variable: interaction P = 0.004). Reductions in body weight were consistent across baseline NTproBNP levels (interaction P = 0.21). In patients with obesity-related HFpEF, semaglutide reduced NTproBNP. Participants with higher baseline NTproBNP had a similar degree of weight loss but experienced larger reductions in HF-related symptoms and physical limitations with semaglutide than those with lower NTproBNP.
IL-7-primed bystander CD8 tumor-infiltrating lymphocytes optimize the antitumor efficacy of T cell engager immunotherapy
Authors: Kun-Joo Lee, Donghoon Choi, Nara Tae, Ha Won Song, Yeon-Woo Kang, Minji Lee, Dain Moon, Youngsik Oh, Sujeong Park, Ji-Hae Kim, Siheon Jeong, Jaehyuk Yang, Uni Park, Da Hee Hong, Mi-Sun Byun, Su-Hyung Park, Joohyuk Sohn, Yunji Park, Sun-Kyoung Im, Sun Shim Choi, Dae Hee Kim, Seung-Woo Lee
Journal: Cell Reports Medicine (2024)

Bispecific T cell engagers (TCEs) show promising clinical efficacy in blood tumors, but their application to solid tumors remains challenging. Here, we show that Fc-fused IL-7 (rhIL-7-hyFc) changes the intratumoral CD8 T cell landscape, enhancing the efficacy of TCE immunotherapy. rhIL-7-hyFc induces a dramatic increase in CD8 tumor-infiltrating lymphocytes (TILs) in various solid tumors, but the majority of these cells are PD-1-negative tumor non-responsive bystander T cells. However, they are non-exhausted and central memory-phenotype CD8 T cells with high T cell receptor (TCR)-recall capacity that can be triggered by tumor antigen-specific TCEs to acquire tumoricidal activity. Single-cell transcriptome analysis reveals that rhIL-7-hyFc-induced bystander CD8 TILs transform into cycling transitional T cells by TCE redirection with decreased memory markers and increased cytotoxic molecules. Notably, TCE treatment has no major effect on tumor-reactive CD8 TILs. Our results suggest that rhIL-7-hyFc treatment promotes the antitumor efficacy of TCE immunotherapy by increasing TCE-sensitive bystander CD8 TILs in solid tumors.
Comprehensive peripheral blood immunoprofiling reveals five immunotypes with immunotherapy response characteristics in patients with cancer
Authors: Daniiar Dyikanov, Aleksandr Zaitsev, Tatiana Vasileva, Iris Wang, Arseniy A. Sokolov, Evgenii S. Bolshakov, Alena Frank, Polina Turova, Olga Golubeva, Anna Gantseva, Anna Kamysheva, Polina Shpudeiko, Ilya Krauz, Mary Abdou, Madison Chasse, Tori Conroy, Nicholas R. Merriam, Julia E. Alesse, Noel English, Boris Shpak, Anna Shchetsova, Evgenii Tikhonov, Ivan Filatov, Anastasia Radko, Anastasiia Bolshakova, Anastasia Kachalova, Nika Lugovykh, Andrey Bulahov, Anastasiia Kilina, Syimyk Asanbekov, Irina Zheleznyak, Pavel Skoptsov, Evgenia Alekseeva, Jennifer M. Johnson, Joseph M. Curry, Alban J. Linnenbach, Andrew P. South, EnJun Yang, Kirill Morozov, Anastasiya Terenteva, Lira Nigmatullina, Dmitry Fastovetz, Anatoly Bobe, Linda Balabanian, Krystle Nomie, Sheila T. Yong, Christopher J.H. Davitt, Alexander Ryabykh, Olga Kudryashova, Cagdas Tazearslan, Alexander Bagaev, Nathan Fowler, Adam J. Luginbuhl, Ravshan I. Ataullakhanov, Michael F. Goldberg
Journal: Cancer Cell (2024)

The lack of comprehensive diagnostics and consensus analytical models for evaluating the status of a patient's immune system has hindered a wider adoption of immunoprofiling for treatment monitoring and response prediction in cancer patients. To address this unmet need, we developed an immunoprofiling platform that uses multiparameter flow cytometry to characterize immune cell heterogeneity in the peripheral blood of healthy donors and patients with advanced cancers. Using unsupervised clustering, we identified five immunotypes with unique distributions of different cell types and gene expression profiles. An independent analysis of 17,800 open-source transcriptomes with the same approach corroborated these findings. Continuous immunotype-based signature scores were developed to correlate systemic immunity with patient responses to different cancer treatments, including immunotherapy, prognostically and predictively. Our approach and findings illustrate the potential utility of a simple blood test as a flexible tool for stratifying cancer patients into therapy response groups based on systemic immunoprofiling.
Correction: Targeting SNORA38B attenuates tumorigenesis and sensitizes immune checkpoint blockade in non-small cell lung cancer by remodeling the tumor microenvironment via regulation of GAB2/AKT/mTOR signaling pathway
Journal: Journal for ImmunoTherapy of Cancer (2024)

Correction: Targeting SNORA38B attenuates tumorigenesis and sensitizes immune checkpoint blockade in non-small cell lung cancer
Tracking in situ checkpoint inhibitor-bound target T cells in patients with checkpoint-induced colitis
Authors: Tarun Gupta, Agne Antanaviciute, Chloe Hyun-Jung Lee, Rosana Ottakandathil Babu, Anna Aulicino, Zoe Christoforidou, Paulina Siejka-Zielinska, Caitlin O’Brien-Ball, Hannah Chen, David Fawkner-Corbett, Ana Sousa Geros, Esther Bridges, Colleen McGregor, Nicole Cianci, Eve Fryer, Nasullah Khalid Alham, Marta Jagielowicz, Ana Mafalda Santos, Martin Fellermeyer, Simon J. Davis, Kaushal Parikh, Vincent Cheung, Lulia Al-Hillawi, Sarah Sasson, Stephanie Slevin, Oliver Brain, Elizabeth Bird-Lieberman, Simona Fourie, Richard Johnston, Heman Joshi, Debabrata Mujamdar, Simon Panter, Nishant Patodi, Sebastian Shaji, Jude Tidbury, Ajay Verma, Ricardo A. Fernandes, Hashem Koohy, Alison Simmons
Journal: Cancer Cell (2024)

The success of checkpoint inhibitors (CPIs) for cancer has been tempered by immune-related adverse effects including colitis. CPI-induced colitis is hallmarked by expansion of resident mucosal IFNγ cytotoxic CD8+ T cells, but how these arise is unclear. Here, we track CPI-bound T cells in intestinal tissue using multimodal single-cell and subcellular spatial transcriptomics (ST). Target occupancy was increased in inflamed tissue, with drug-bound T cells located in distinct microdomains distinguished by specific intercellular signaling and transcriptional gradients. CPI-bound cells were largely CD4+ T cells, including enrichment in CPI-bound peripheral helper, follicular helper, and regulatory T cells. IFNγ CD8+ T cells emerged from both tissue-resident memory (TRM) and peripheral populations, displayed more restricted target occupancy profiles, and co-localized with damaged epithelial microdomains lacking effective regulatory cues. Our multimodal analysis identifies causal pathways and constitutes a resource to inform novel preventive strategies.
Hormesis as an adaptive response to infection
Authors: Michael Bauer, Maria Ermolaeva, Mervyn Singer, Reinhard Wetzker, Miguel P. Soares
Journal: Trends in Molecular Medicine (2024)

Hormesis is a phenomenon whereby low-level stress can improve cellular, organ, or organismal fitness in response to a subsequent similar or other stress insult. Whereas hormesis is thought to contribute to the fitness benefits arising from symbiotic host-microbe interactions, the putative benefits of hormesis in host-pathogen interactions have yet to be explored. Hormetic responses have nonetheless been reported in experimental models of infection, a common feature of which is regulation of host mitochondrial function. We propose that these mitohormetic responses could be harnessed therapeutically to limit the severity of infectious diseases.
Pesticide reduction: clustering organic croplands
Authors: Muhammad Waqas, Chen Yaning, Nicolas Desneux
Journal: Trends in Ecology & Evolution (2024)

Organic and conventional farms often coexist, yet their proximity does not ensure compatibility. Larsen et al. reveal that being surrounded by organic fields reduces pesticide usage in organic fields but increases it in conventional fields. We discuss these findings, emphasizing the need to cluster organic croplands for reduced pesticide use.