tbuckley/cabot-search huggingface dataset:
Autosomal recessive plantar keratoderma with ragged periungual hyperkeratosis caused by a homozygous missense variant in <i>KRT16</i>
Authors: Arti Nanda, Yi-Han Chang, Hui-Ching Cheng, I Tzu Lai, Atlal Al-Lafi, John A McGrath, Chao-Kai Hsu
Journal: British Journal of Dermatology (2024)

In the present study, we report a consanguineous Kuwaiti pedigree with pseudo-dominant inheritance of a recessive KRT16 variant in which homozygotes had focal nonepidermolytic palmoplantar keratoderma accompanied by ragged periungual hyperkeratosis. The key value of this submission is that we believe we have identified the first autosomal recessive inherited skin disorder resulting from pathogenic variants in the keratin 16 gene, KRT16. Our findings expand both the genetic basis and phenotypic expression of inherited KRT16-related disorders.
Single-cell transcriptome landscape of circulating CD4+ T cell populations in autoimmune diseases
Authors: Yoshiaki Yasumizu, Daiki Takeuchi, Reo Morimoto, Yusuke Takeshima, Tatsusada Okuno, Makoto Kinoshita, Takayoshi Morita, Yasuhiro Kato, Min Wang, Daisuke Motooka, Daisuke Okuzaki, Yamami Nakamura, Norihisa Mikami, Masaya Arai, Xuan Zhang, Atsushi Kumanogoh, Hideki Mochizuki, Naganari Ohkura, Shimon Sakaguchi
Journal: Cell Genomics (2024)

CD4+ T cells are key mediators of various autoimmune diseases; however, their role in disease progression remains unclear due to cellular heterogeneity. Here, we evaluated CD4+ T cell subpopulations using decomposition-based transcriptome characterization and canonical clustering strategies. This approach identified 12 independent gene programs governing whole CD4+ T cell heterogeneity, which can explain the ambiguity of canonical clustering. In addition, we performed a meta-analysis using public single-cell datasets of over 1.8 million peripheral CD4+ T cells from 953 individuals by projecting cells onto the reference and cataloging cell frequency and qualitative alterations of the populations in 20 diseases. The analyses revealed that the 12 transcriptional programs were useful in characterizing each autoimmune disease and predicting its clinical status. Moreover, genetic variants associated with autoimmune diseases showed disease-specific enrichment within the 12 gene programs. The results collectively provide a landscape of single-cell transcriptomes of CD4+ T cell subpopulations involved in autoimmune disease.
Sodium-Glucose Cotransport Protein 2 Inhibitors in Patients With Type 2 Diabetes and Acute Kidney Disease
Authors: Heng-Chih Pan, Jui-Yi Chen, Hsing-Yu Chen, Fang-Yu Yeh, Thomas Tao-Min Huang, Chiao-Yin Sun, Shiow-Ing Wang, James Cheng-Chung Wei, Vin-Cent Wu
Journal: JAMA Network Open (2024)

Importance Sodium-glucose cotransport protein 2 inhibitors (SGLT-2is) have demonstrated associations with positive kidney-related and cardiovascular outcomes in patients with type 2 diabetes. However, the association of SGLT-2is with outcomes among patients with type 2 diabetes and acute kidney disease (AKD) remains unclear. Objective To examine the long-term associations of SGLT-2is with mortality, major adverse kidney events (MAKEs), and major adverse cardiovascular events (MACEs) in patients with type 2 diabetes and AKD. Design, Setting, and Participants This cohort study used global health care data (the TriNetX database) spanning from September 30, 2002, to September 30, 2022. Propensity score matching was used to select a cohort of patients, and follow-up was conducted with a maximum duration of 5 years (completed on September 30, 2022) or until the occurrence of an outcome or death. Intervention The use of SGLT-2is. Main Outcomes and Measures The primary outcomes measured were mortality, MAKEs, and MACEs. Adjusted hazard ratios (AHR) with 95% CIs were calculated to compare the risks between SGLT-2i users and nonusers, representing the mean treatment effect among the treated patients. Results A total of 230 366 patients with AKD (mean [SD] age, 67.1 [16.4] years; 51.8% men and 48.2% women) were enrolled in the study, which had a median follow-up duration of 2.3 (IQR, 1.2-3.5) years. Among these, 5319 individuals (2.3%) were identified as SGLT-2i users. Among nonusers, the incidence of mortality was 18.7%, the incidence of MAKEs was 21.0%, and the incidence of MACEs was 25.8%. After propensity score matching, the absolute differences between SGLT-2i users and nonusers for incidence of mortality, MAKEs, and MACEs were 9.7%, 11.5%, and 12.3%, respectively. Based on the treated population, SGLT-2i use was associated with a significantly lower risk of mortality (AHR, 0.69 [95% CI, 0.62-0.77]), MAKEs (AHR, 0.62 [95% CI, 0.56-0.69]), and MACEs (AHR, 0.75 [95% CI, 0.65-0.88]) compared with nonuse. External validation using a multicenter cohort data set of 1233 patients with AKD patients who were SGLT-2i users confirmed the observed beneficial outcomes. Notably, the risk reduction associated with SGLT-2is remained significant even among patients without hypertension, those with advanced chronic kidney disease, and those not receiving other hypoglycemic agents. Conclusions and Relevance In this cohort study of patients with type 2 diabetes and AKD, administration of SGLT-2is was associated with a significant reduction in all-cause mortality, MAKEs, and MACEs when compared with nonuse, underscoring the importance of SGLT-2is in care after acute kidney injury. These findings emphasize the potential benefits of SGLT-2is in managing AKD and mitigating the risks of major cardiovascular and kidney diseases.
Improving the Integrity of Surgical Education Scholarship
Authors: Amalia Cochran, Dimitrios Stefanidis, Melina R. Kibbe
Journal: JAMA Surgery (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Lived Experience of Acne and Acne Treatment in Transgender Patients
Authors: Sarah Gold, Meron Siira, Sigal Willner, Crescent Alcid, Suephy C. Chen, Vin Tangpricha, Michael Goodman, Cam Escoffery, Ashli Owen-Smith, Howa Yeung
Journal: JAMA Dermatology (2024)

While acne is common in transgender and gender-diverse people and is associated with gender-affirming hormone therapy, little research has examined these factors and their impact in gender minority groups.
Lipid Management and Interactions with Immunosuppressants in Patients Undergoing Kidney Transplant: Opinions and Prospects
Authors: Yanqin Li, Fan Luo, Qi Gao, Licong Su
Journal: Journal of the American Society of Nephrology (2024)

We appreciate the work of Bae et al.,1 which we have diligently perused. The authors conducted a large, retrospective cohort study involving 58,264 recipients of kidney transplant (KT), followed for over 4 years. Their noteworthy findings indicate a significant association between statin use and reduced all-cause mortality risk against the backdrop of substantial influence of specific immunosuppression agents. Following are the comments on this noteworthy contribution. Primarily, the study maximally adjusted potential confounders to balance statin indications. However, several important factors should not be overlooked, including dynamic blood lipid levels during follow-up as well as antithrombotic, lipid-lowering, antidiabetic, and antihypertensive treatments. In addition, statin exposure (including any statin prescription after KT) might introduce an immortal time bias, granting a survival advantage to the exposed group. Given these uncertainties, we recommend using target trial emulation methods to enhance the robustness of the results.2 Furthermore, the study revealed a protective effect of statins on mortality among cyclosporine users, mammalian target of rapamycin inhibitors users, and mycophenolate mofetil (MMF) non-users. These findings may lead to a preference for mammalian target of rapamycin inhibitors combination therapy. However, the prevailing practice is triple immunosuppressive therapy after kidney transplantation (tacrolimus/cyclosporine plus MMF and corticosteroids).3 Thus, it is necessary to show the specific details of the drug combination. Relying solely on single-agent categorization potentially limits the understanding of why statins are more efficacious in users of non–calcineurin inhibitors or MMF. Insight into the practical immunosuppressive regimen could enhance the clinical significance of statin management in mitigating adverse outcomes. In addition, the adverse effects of statins on hard clinical outcomes among patients receiving KT were not observed in previous investigations. Meanwhile, the Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guidelines still recommend that all adult recipients of KT receive statin treatment.4 Therefore, future studies should focus on the effect of statins, especially the new lipid-lowering drugs, such as proprotein convertase subtilisin/kexin type 9 inhibitors, with different immunosuppressive therapies in patients receiving KT.
Authors' Reply: Lipid Management and Interactions with Immunosuppressants in Kidney Transplant Patients: Some Opinions and Prospects
Authors: Sunjae Bae, Mara A. McAdams-DeMarco
Journal: Journal of the American Society of Nephrology (2024)

We thank Dr. Li and colleagues for their feedback on our study.1 The authors suggested adjusting for lipid levels to lower the risk of confounding by indication. We fully agree with this assessment and have remarked the absence of such variables in our transplant-oriented dataset as a limitation of our study (Discussion, Paragraph 5).2 Despite this limitation, however, we believe our design is aligned with the Kidney Disease Improving Global Outcomes guidelines,3 which recommend statin therapy for all adult recipients of kidney transplant. Moreover, the potential confounding by indication would have channeled the high-risk recipients to the statin user group, leading to a conservatively biased estimate of the protective effect. We do not find the modest strength of the protective association itself to be a reason to revisit our statistical analysis. In addition, immortal time bias is likely not a concern because statin use was treated as a time-varying exposure; the person-time before statin initiation was assigned to the non-user group, and only that after statin initiation was assigned to the statin user group (Methods, "Statin Use" section). This is a common approach to avoid immortal time bias.4 We also agree with the authors that statins should ultimately be studied in conjunction with other cardiovascular medications (e.g., antihypertensives and antidiabetics) and with immunosuppressive regimens (versus individual agents). As noted in our study (Discussion, Paragraph 4), we view such a multidimensional approach as the clear next step for future research, rather than the objective of the current study. This approach necessitates a different analytical approach that can systematically account for the interactions between the medications, such as a factorial design or a machine learning algorithm with a robust interaction analysis. We would like to once again thank Dr. Li and colleagues for their insightful comments. We highly look forward to addressing these research questions with datasets with richer cardiovascular information and advanced analytic techniques that can examine multiple interventions and their interactions.
Pathogenic, Total Loss-of-Function <i>DYRK1B</i> Variants Cause Monogenic Obesity Associated With Type 2 Diabetes
Authors: Lise Folon, Morgane Baron, Victoria Scherrer, Bénédicte Toussaint, Emmanuel Vaillant, Hélène Loiselle, Aurélie Dechaume, Frédérique De Pooter, Raphaël Boutry, Mathilde Boissel, Aboubacar Diallo, Lijiao Ning, Beverley Balkau, Guillaume Charpentier, Sylvia Franc, Michel Marre, Mehdi Derhourhi, Philippe Froguel, Amélie Bonnefond
Journal: Diabetes Care (2024)

OBJECTIVE Rare variants in DYRK1B have been described in some patients with central obesity, type 2 diabetes, and early-onset coronary disease. Owing to the limited number of conducted studies, the broader impact of DYRK1B variants on a larger scale has yet to be investigated. RESEARCH DESIGN AND METHODS DYRK1B was sequenced in 9,353 participants from a case-control study for obesity and type 2 diabetes. Each DYRK1B variant was functionally assessed in vitro. Variant pathogenicity was determined using criteria from the American College of Medical Genetics and Genomics (ACMG). The effect of pathogenic or likely pathogenic (P/LP) variants on metabolic traits was assessed using adjusted mixed-effects score tests. RESULTS Sixty-five rare, heterozygous DYRK1B variants were identified and were not associated with obesity or type 2 diabetes. Following functional analyses, 20 P/LP variants were pinpointed, including 6 variants that exhibited a fully inhibitory effect (P/LP-null) on DYRK1B activity. P/LP and P/LP-null DYRK1B variants were associated with increased BMI and obesity risk; however, the impact was notably more pronounced for the P/LP-null variants (effect of 8.0 ± 3.2 and odds ratio of 7.9 [95% CI 1.2–155]). Furthermore, P/LP-null variants were associated with higher fasting glucose and type 2 diabetes risk (effect of 2.9 ± 1.0 and odds ratio of 4.8 [95% CI 0.85–37]), while P/LP variants had no effect on glucose homeostasis. CONCLUSIONS P/LP, total loss-of-function DYRK1B variants cause monogenic obesity associated with type 2 diabetes. This study underscores the significance of conducting functional assessments in order to accurately ascertain the tangible effects of P/LP DYRK1B variants.
Calcium Scoring Improves Clinical Management in Patients With Low Clinical Likelihood of Coronary Artery Disease
Authors: Gitte S. Brix, Laust D. Rasmussen, Palle D. Rohde, Samuel E. Schmidt, Mette Nyegaard, Pamela S. Douglas, David E. Newby, Michelle C. Williams, Borek Foldyna, Juhani Knuuti, Morten Bøttcher, Simon Winther
Journal: JACC. Cardiovascular imaging (2024)
Ultrasound Blood–Brain Barrier Opening and Aducanumab in Alzheimer’s Disease
Authors: Ali R. Rezai, Pierre-Francois D’Haese, Victor Finomore, Jeffrey Carpenter, Manish Ranjan, Kirk Wilhelmsen, Rashi I. Mehta, Peng Wang, Umer Najib, Camila Vieira Ligo Teixeira, Tasneem Arsiwala, Abdul Tarabishy, Padmashree Tirumalai, Daniel O. Claassen, Sally Hodder, Marc W. Haut
Journal: New England Journal of Medicine (2024)

Antiamyloid antibodies have been used to reduce cerebral amyloid-beta (Aβ) load in patients with Alzheimer's disease. We applied focused ultrasound with each of six monthly aducanumab infusions to temporarily open the blood-brain barrier with the goal of enhancing amyloid removal in selected brain regions in three participants over a period of 6 months. The reduction in the level of Aβ was numerically greater in regions treated with focused ultrasound than in the homologous regions in the contralateral hemisphere that were not treated with focused ultrasound, as measured by fluorine-18 florbetaben positron-emission tomography. Cognitive tests and safety evaluations were conducted over a period of 30 to 180 days after treatment. (Funded by the Harry T. Mangurian, Jr. Foundation and the West Virginia University Rockefeller Neuroscience Institute.).
APRIL — Springtime for New IgA Nephropathy Therapy?
Authors: Kevin V Lemley, Richard J Glassock
Journal: New England Journal of Medicine (2024)

IgA nephropathy is the most common primary glomerulonephritis in most of the world. It typically manifests in childhood or young adulthood. Although it has substantial clinical heterogeneity, it has been considered to be a slowly progressive disease1 among patients without risk indicators such as high-grade proteinuria, marked hypertension, and specific biopsy findings. After a risk assessment is performed on the basis of a kidney biopsy (with the use of the Oxford Classification MEST-C score, which is based on the presence of mesangial [M] and endocapillary [E] hypercellularity, segmental sclerosis [S], interstitial fibrosis or tubular atrophy [T], and crescents [C]) and . . .
Virological characteristics of the SARS-CoV-2 JN.1 variant
Authors: Yu Kaku, Kaho Okumura, Miguel Padilla-Blanco, Yusuke Kosugi, Keiya Uriu, Alfredo A Hinay, Luo Chen, Arnon Plianchaisuk, Kouji Kobiyama, Ken J Ishii, Jiri Zahradnik, Jumpei Ito, Kei Sato
Journal: The Lancet Infectious Diseases (2024)
Clarithromycin for early anti-inflammatory responses in community-acquired pneumonia in Greece (ACCESS): a randomised, double-blind, placebo-controlled trial
Authors: Evangelos J Giamarellos-Bourboulis, Athanasios Siampanos, Amalia Bolanou, Sarantia Doulou, Nikolaos Kakavoulis, Konstantinos Tsiakos, Sokratis Katopodis, Georgios Schinas, Lamprini Skorda, Zoi Alexiou, Konstantinos Armenis, Paraskevi Katsaounou, George Chrysos, Aikaterini Masgala, Garyphalia Poulakou, Nikolaos Antonakos, Asimina Safarika, Miltiades Kyprianou, Konstantina Dakou, Styliani Gerakari, Ilias C Papanikolaou, Haralampos Milionis, Markos Marangos, George N Dalekos, Vasiliki Tzavara, Karolina Akinosoglou, Eryfilli Hatziaggelaki, Styliani Sympardi, Theano Kontopoulou, Maria Mouktaroudi, Antonios Papadopoulos, Michael S Niederman
Journal: The Lancet Respiratory Medicine (2024)
Involving older people in the preparedness, response, and recovery phases in humanitarian emergencies: a theoretical framework on ageism, epistemic injustice, and participation
Authors: Elburg van Boetzelaer, Judith van de Kamp, Patrick Keating, Sunita Sharma, Umberto Pellecchia, Joyce L Browne, Julian Sheather, Oscar H Franco
Journal: The Lancet Healthy Longevity (2024)

Humanitarian emergencies disproportionally affect older people. Although defining an older person by an age range can help alert us to emerging or changing needs and potential vulnerabilities during humanitarian emergencies, ageing is not necessarily synonymous with increasing vulnerability, and individual variations exist due to the heterogeneity of older people. In general, reduced access to safety, health services, clean water, and appropriate food puts older people at increased risk of poor health outcomes during humanitarian emergencies, including disability, injury, malnutrition, and mental health issues. The theoretical framework presented in this Personal View explains how ageism, further compounded by intersecting oppression, leads to the exclusion of older people from the preparedness, response, and recovery phases of humanitarian emergencies. The exclusion of older people is discriminatory, violates core humanitarian and bioethical principles, and leads to an epistemic injustice. We suggest that humanitarian actors implement participatory approaches with older people in humanitarian contexts. Through these approaches, solutions will be identified by and together with older people, leading to community-driven and context-appropriate ways to include the needs and strengths of older people in the preparedness, response, and recovery phases of humanitarian emergencies.
Association between hearing aid use and mortality in adults with hearing loss in the USA: a mortality follow-up study of a cross-sectional cohort
Authors: Janet S Choi, Meredith E Adams, Eileen M Crimmins, Frank R Lin, Jennifer A Ailshire
Journal: The Lancet Healthy Longevity (2024)

BackgroundHearing loss has been identified as an independent risk factor for negative health outcomes and mortality. However, whether rehabilitation with hearing aid use is associated with lower mortality is currently unknown. This study aimed to examine the associations of hearing loss, hearing aid use, and mortality in the USA.MethodsIn this cross-sectional, follow-up study, we assessed 9885 adults (age 20 years and older) who participated in the National Health and Nutrition Examination Survey between 1999 and 2012 and completed audiometry and hearing aid use questionnaires (1863 adults with hearing loss). Main measures included hearing loss (speech-frequency pure-tone average) and hearing aid use (never users, non-regular users, and regular users). Mortality status of the cohort was linked to the National Death Index up to Dec 31, 2019. Cox proportional regression models were used to examine the association between hearing loss, hearing aid use, and mortality while adjusting for demographics and medical history.FindingsThe cohort consisted of 9885 participants, of which 5037 (51·0%) were female and 4848 (49·0%) were male with a mean age of 48·6 years (SD 18·1) at baseline. The weighted prevalence of audiometry-measured hearing loss was 14·7% (95% CI 13·3–16·3%) and the all-cause mortality rate was 13·2% (12·1–14·4) at a median 10·4 years of follow-up (range 0·1–20·8). The rate of regular hearing aid use among adults with hearing loss was 12·7% (95% CI 10·6–15·1). Hearing loss was an independent risk factor associated with higher mortality (adjusted hazard ratio [HR] 1·40 [95% CI 1·21–1·62]). Among individuals with hearing loss, the adjusted mortality risk was lower among regular hearing aid users in comparison with never users (adjusted HR 0·76 [0·60–0·95]) accounting for demographics, hearing levels, and medical history. There was no difference in adjusted mortality between non-regular hearing aid users and never users (adjusted HR 0·93 [0·70–1·24]).InterpretationRegular hearing aid use was associated with lower risks of mortality than in never users in US adults with hearing loss when accounting for age, hearing loss, and other potential confounders. Future research is needed to investigate the potential protective role of hearing aid use against mortality for adults with hearing loss.FundingNone
Segmentectomy versus lobectomy in small-sized peripheral non-small-cell lung cancer with radiologically pure-solid appearance in Japan (JCOG0802/WJOG4607L): a post-hoc supplemental analysis of a multicentre, open-label, phase 3 trial
Authors: Aritoshi Hattori, Kenji Suzuki, Kazuya Takamochi, Masashi Wakabayashi, Yuta Sekino, Yasuhiro Tsutani, Ryu Nakajima, Keiju Aokage, Hisashi Saji, Masahiro Tsuboi, Morihito Okada, Hisao Asamura, Kenichi Nakamura, Haruhiko Fukuda, Shun-ichi Watanabe, Jiro Okami, Hiroyuki Ito, Kazuo Nakagawa, Hiroshige Yoshioka, Makoto Endo, Mitsuhiro Isaka, Takahiro Mimae, Tomohiro Miyoshi
Journal: The Lancet Respiratory Medicine (2024)
Optimising the vaccine strategy of BCG, ChAdOx1 85A, and MVA85A for tuberculosis control
Authors: Anne Wajja, Beatrice Nassanga, Agnes Natukunda, Joel Serubanja, Josephine Tumusiime, Helen Akurut, Gloria Oduru, Jacent Nassuuna, Joyce Kabagenyi, Hazel Morrison, Hannah Scott, Rebecca Powell Doherty, Julia L Marshall, Ingrid Cabrera Puig, Stephen Cose, Pontiano Kaleebu, Emily L Webb, Iman Satti, Helen McShane, Alison M Elliott
Journal: The Lancet Infectious Diseases (2024)