tbuckley/cabot-search huggingface dataset:
<i>UBA1</i> Variations in Neutrophilic Dermatosis Skin Lesions of Patients With VEXAS Syndrome
Authors: Eve Zakine, Bérénice Schell, Maxime Battistella, Marie-Dominique Vignon-Pennamen, François Chasset, Thibault Mahévas, Florence Cordoliani, Lionel Adès, Marie Sébert, Jérémie Delaleu, Marie Jachiet, Clémence Lepelletier, Pierre Lemaire, Clémentine Chauvel, Bedis Dhouaieb, Rathana Kim, Charles Cassius, Sophie Georgin-Lavialle, Arsène Mekinian, Martine Bagot, Thorsten Braun, Laurie Rousset, Edouard Begon, Adèle de Masson, Pierre Fenaux, Emmanuelle Clappier, Jean-David Bouaziz
Journal: JAMA Dermatology (2021)

<h3>Importance</h3> VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a recently described severe adult-onset autoinflammatory disease that is associated with myeloid lineage-restricted ubiquitin-activating enzyme 1 (<i>UBA1</i>) somatic variations that primarily affect the skin (Sweet syndrome), cartilage, and bone marrow. Skin symptoms have been poorly described. <h3>Objective</h3> To better describe clinical and pathological skin manifestations and their pathophysiology in VEXAS syndrome. <h3>Design, Setting, and Participants</h3> This multicenter retrospective case series study of clinical and histological features of 8 patients with VEXAS syndrome and skin involvement was conducted in France from December 2007 to March 2021, with molecular data obtained from March to April 2022. Any<i>UBA1</i>variations were detected by Sanger or next-generation sequencing that was performed on bone marrow and formalin-fixed paraffin-embedded tissue sections of skin lesion biopsies. <h3>Results</h3> All 8 patients were men, and the median age at symptom onset was 65.5 years (interquartile range, 54-76 years). All patients had neutrophilic dermatosis skin lesions, including tender red or violaceous papules, sometimes edematous, without fever, arthralgia, recurrence or pathergy, inflammatory edematous papules on the neck and trunk (sometimes umbilicated), and firm erythematous purpuric or pigmented infiltrated plaques and nodules. Three patients had livedo racemosa. The infiltrates were perivascular and consisted of mature neutrophils with leukocytoclasia, which were admixed with myeloperoxidase-positive CD163-positive myeloid cells with indented nuclei and lymphoid cells in all cases. A sequencing analysis of paired bone marrow samples and skin lesion biopsies identified the same loss-of-function<i>UBA1</i>variation in both samples for all patients. <h3>Conclusions and Relevance</h3> This case series study describes the different clinical presentations of skin lesions found in VEXAS syndrome, which is characterized histologically by neutrophilic dermatosis. The findings suggested that the dermal infiltrates seen in VEXAS skin lesions are derived from the pathological myeloid clone. This suggests that using therapies that target the pathological clone may be effective in the long-term management of the disease.
A mitochondrial membrane-bridging machinery mediates signal transduction of intramitochondrial oxidation
Authors: Li Li, Devon M. Conradson, Vinita Bharat, Min Joo Kim, Chung-Han Hsieh, Paras S. Minhas, Amanda M. Papakyrikos, Aarooran Sivakumaran Durairaj, Anthony Ludlam, Katrin I. Andreasson, Linda Partridge, Michael A. Cianfrocco, Xinnan Wang
Journal: Nature Metabolism (2021)
Preliminary evidence for the presence of multiple forms of cell death in diabetes cardiomyopathy
Authors: Jinjing Wei, Yongting Zhao, Haihai Liang, Weijie Du, Lihong Wang
Journal: Acta Pharmaceutica Sinica B (2021)

Diabetic mellitus (DM) is a common degenerative chronic metabolic disease often accompanied by severe cardiovascular complications (DCCs) as major causes of death in diabetic patients with diabetic cardiomyopathy (DCM) as the most common DCC. The metabolic disturbance in DCM generates the conditions/substrates and inducers/triggers and activates the signaling molecules and death executioners leading to cardiomyocyte death which accelerates the development of DCM and the degeneration of DCM to heart failure. Various forms of programmed active cell death including apoptosis, pyroptosis, autophagic cell death, autosis, necroptosis, ferroptosis and entosis have been identified and characterized in many types of cardiac disease. Evidence has also been obtained for the presence of multiple forms of cell death in DCM. Most importantly, published animal experiments have demonstrated that suppression of cardiomyocyte death of any forms yields tremendous protective effects on DCM. Herein, we provide the most updated data on the subject of cell death in DCM, critical analysis of published results focusing on the pathophysiological roles of cell death, and pertinent perspectives of future studies.
The oral microbiome: Role of key organisms and complex networks in oral health and disease
Authors: Lea Sedghi, Vincent DiMassa, Anthony Harrington, Susan V. Lynch, Yvonne L. Kapila
Journal: Periodontology 2000 (2021)

Abstract States of oral health and disease reflect the compositional and functional capacities of, as well as the interspecies interactions within, the oral microbiota. The oral cavity exists as a highly dynamic microbial environment that harbors many distinct substrata and microenvironments that house diverse microbial communities. Specific to the oral cavity, the nonshedding dental surfaces facilitate the development of highly complex polymicrobial biofilm communities, characterized not only by the distinct microbes comprising them, but cumulatively by their activities. Adding to this complexity, the oral cavity faces near‐constant environmental challenges, including those from host diet, salivary flow, masticatory forces, and introduction of exogenous microbes. The composition of the oral microbiome is shaped throughout life by factors including host genetics, maternal transmission, as well as environmental factors, such as dietary habits, oral hygiene practice, medications, and systemic factors. This dynamic ecosystem presents opportunities for oral microbial dysbiosis and the development of dental and periodontal diseases. The application of both in vitro and culture‐independent approaches has broadened the mechanistic understandings of complex polymicrobial communities within the oral cavity, as well as the environmental, local, and systemic underpinnings that influence the dynamics of the oral microbiome. Here, we review the present knowledge and current understanding of microbial communities within the oral cavity and the influences and challenges upon this system that encourage homeostasis or provoke microbiome perturbation, and thus contribute to states of oral health or disease.
Mortality risk in transgender people is twice as high as in cisgender people, data show
Authors: Jacqui Wise
Journal: BMJ (2021)

The mortality risk in transgender people using hormone treatment is twice as high as in cisgender people and has not decreased in the past five decades, a Dutch retrospective analysis has suggested.1

However, the researchers concluded that the increased mortality risk in transgender people did not seem to be a specific effect of gender affirming hormone treatment.

Transgender people often seek medical treatment to bring about physical changes that more closely match their gender identify, and this can include hormone treatment and surgery. For transgender women, gender affirming hormone treatment consists of oestrogen in combination with a testosterone lowering medication. For transgender men gender affirming hormone treatment consists of testosterone.

The study, published in the Lancet Diabetes & Endocrinology ,1 included 2927 transgender women and 1641 transgender men who visited the gender identity clinic of Amsterdam University Medical Centre …
P-228 Phase II multicentric randomized controlled trial to compare first-line treatment with FOLFOX6m + mAB alone or in combination with liver chemoembolization (Lifepearls-Irinotecan) in poor prognosis colorectal cancer with liver-limited disease
Authors: D. Paez, F. Gomez, J. Maurel, A. Virgili, V. Baños, H. Oliveres, E. Carrero, R. Guerrero, E. Pineda
Journal: Annals of Oncology (2021)
Case-mix adjustment to compare colonoscopy performance between endoscopy centers: a nationwide registry study
Authors: Karlijn J. Nass, Manon van der Vlugt, Arthur K. E. Elfrink, Crispijn L. van den Brand, Janneke A. Wilschut, Paul Fockens, Evelien Dekker, Michel W. J. M. Wouters
Journal: Endoscopy (2021)

BACKGROUND : Nonmodifiable patient and endoscopy characteristics might influence colonoscopy performance. Differences in these so-called case-mix factors are likely to exist between endoscopy centers. This study aimed to examine the importance of case-mix adjustment when comparing performance between endoscopy centers. METHODS : Prospectively collected data recorded in the Dutch national colonoscopy registry between 2016 and 2019 were retrospectively analyzed. Cecal intubation rate (CIR) and adequate bowel preparation rate (ABPR) were analyzed. Additionally, polyp detection rate (PDR) was studied in screening colonoscopies following a positive fecal immunochemical test (FIT). Variation in case-mix factors between endoscopy centers and expected outcomes for each performance measure were calculated per endoscopy center based on case-mix factors (sex, age, American Society of Anesthesiologist [ASA] score, indication) using multivariable logistic regression. RESULTS: 363 840 colonoscopies were included from 51 endoscopy centers. Mean percentages per endoscopy center were significantly different for age > 65 years, male patients, ASA ≥ III, and diagnostic colonoscopies (all P < 0.001). In the FIT-positive screening population, significant differences were observed between endoscopy centers for age > 65 years, male patients, and ASA ≥ III (all P ≤ 0.001). The expected CIR, ABPR, and PDR ranged from 95.0 % to 96.9 %, from 93.6 % to 96.4 %, and from 76.2 % to 79.1 %, respectively. Age, sex, ASA classification, and indication were significant case-mix factors for CIR and ABPR. In the FIT-positive screening population, age, sex, and ASA classification were significant case-mix factors for PDR. CONCLUSION: Our findings emphasize the importance of considering case-mix adjustment when comparing colonoscopy performance measures between endoscopy centers.
The 5-Year Paradigm in DCIS of the Breast: Unexpected Lessons From the NSABP B-43 Trial
Authors: Mieke R. Van Bockstal, Louis Libbrecht, Christine Galant
Journal: Journal of Clinical Oncology (2021)

Cobleigh et al 1 have reported on the phase III NSABP B-43 trial.This unique randomized cohort provides the first data on the effectiveness of a dual dose of trastuzumab when added to adjuvant whole-breast irradiation after lumpectomy for human epidermal growth factor receptor 2-positive ductal carcinoma in situ (DCIS). 1 As the number of ipsilateral breast tumor recurrences (IBTRs) in this extensive cohort was lower than originally estimated, the initially proposed 36% reduction in the IBTR hazard ratio was not achieved. 1lthough not statistically significant, adjuvant trastuzumab was nevertheless associated with a 19% reduction in IBTRs.Subgroup analysis showed that this was because of a marked reduction in in situ IBTRs, without effect on invasive IBTRs. 1 Although the authors mentioned two explanations, we would like to highlight another interpretation of this observation.
Multiomics: unraveling the panoramic landscapes of SARS-CoV-2 infection
Authors: Xin Wang, Gang Xu, Xiaoju Liu, Yang Liu, Shuye Zhang, Zheng Zhang
Journal: Cellular and Molecular Immunology (2021)

Abstract In response to emerging infectious diseases, such as the recent pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is critical to quickly identify and understand responsible pathogens, risk factors, host immune responses, and pathogenic mechanisms at both the molecular and cellular levels. The recent development of multiomic technologies, including genomics, proteomics, metabolomics, and single-cell transcriptomics, has enabled a fast and panoramic grasp of the pathogen and the disease. Here, we systematically reviewed the major advances in the virology, immunology, and pathogenic mechanisms of SARS-CoV-2 infection that have been achieved via multiomic technologies. Based on well-established cohorts, omics-based methods can greatly enhance the mechanistic understanding of diseases, contributing to the development of new diagnostics, drugs, and vaccines for emerging infectious diseases, such as COVID-19.
Challenges of Sarcoidosis and Its Management
Authors: Marjolein Drent, Elliott D. Crouser, Johan Grunewald
Journal: New England Journal of Medicine (2021)

Sarcoidosis is a lung disease of unknown cause characterized by noncaseating granulomas; the heart and nervous system may also be involved. It is often misdiagnosed; tissue biopsy is needed for a definitive diagnosis. Glucocorticoids are recommended as initial treatment, when needed, but not for long-term care.
Association of Bone Erosions and Osteophytes With Systemic Bone Involvement on <scp>High‐Resolution</scp> Peripheral Quantitative Computed Tomography in Premenopausal Women With Longstanding Rheumatoid Arthritis
Authors: Mariana O. Perez, Camille P. Figueiredo, Lucas P. Sales, Ana Cristina Medeiros‐Ribeiro, Liliam Takayama, Diogo S. Domiciano, Karina Bonfiglioli, Valeria F. Caparbo, Rosa M. R. Pereira
Journal: Arthritis & Rheumatology (2021)

To evaluate premenopausal women with longstanding rheumatoid arthritis (RA) for potential associations between parameters of localized bone involvement and parameters of systemic bone involvement in the affected joints.Eighty consecutively evaluated premenopausal women with RA were included in the study, along with 160 healthy female control subjects who were matched to the patients by age and body mass index. Volumetric bone mineral density (vBMD), bone microarchitecture, and finite elements of biomechanical bone strength (bone stiffness and estimated failure load) at the distal radius and distal tibia were analyzed by high-resolution peripheral quantitative computed tomography (HR-pQCT) in patients with RA compared to healthy controls. In addition, in patients with RA, localized bone involvement in the metacarpophalangeal and proximal interphalangeal joints was analyzed by HR-pQCT, to identify bone erosions and osteophytes.Among the 80 premenopausal women with longstanding RA, the mean ± SD age was 39.4 ± 6.7 years and mean ± SD disease duration was 9.8 ± 5.3 years. Trabecular and cortical bone parameters and bone strength at the distal radius and distal tibia were all impaired in patients with RA compared to healthy controls (each P < 0.05). In total, 75% of RA patients had evidence of bone erosions, and 41.3% of RA patients had detectable osteophytes on HR-pQCT. RA patients with bone erosions, as compared to RA patients without bone erosions, had lower cortical vBMD (at the distal radius, mean ± SD 980 ± 72 mg HA/cm3 versus 1,021 ± 47 mg HA/cm3 [P = 0.03]; at the distal tibia, 979 ± 47 mg HA/cm3 versus 1,003 ± 34 mg HA/cm3 [P = 0.04]) and higher cortical bone porosity (at the distal radius, mean ± SD 2.8 ± 2.5% versus 1.8 ± 1.6% [P = 0.04]; at the distal tibia, 3.7 ± 1.6% versus 2.7 ± 1.6% [P = 0.01]). In patients with RA, osteophyte volume at the distal radius was positively correlated with trabecular vBMD (r = 0.392, P = 0.02), trabecular number (r = 0.381, P = 0.03), and trabecular stiffness (r = 0.411, P = 0.02), and negatively correlated with trabecular separation (r = -0.364, P = 0.04), as determined by Pearson's or Spearman's correlation test.The findings show that premenopausal women with longstanding RA have systemic bone fragility at peripheral joint sites. Moreover, the presence of bone erosions is mainly associated with cortical bone fragility at the distal radius and tibia, and presence of osteophytes is associated with repair of trabecular bone at the distal radius.
National Evaluation of the Association Between Resident Labor Union Participation and Surgical Resident Well-being
Authors: Brian C. Brajcich, Jeanette W. Chung, Douglas E. Wood, Karen D. Horvath, Philip D. Tolley, Elizabeth F. Yates, Chandrakanath Are, Ryan J. Ellis, Yue-Yung Hu, Karl Y. Bilimoria
Journal: JAMA Network Open (2021)

Labor unions are purported to improve working conditions; however, little evidence exists regarding the effect of resident physician unions.
Racial and Ethnic Disparities in Comorbidities in Youth With Type 2 Diabetes in the Pediatric Diabetes Consortium (PDC)
Authors: Fida Bacha, Peiyao Cheng, Robin L. Gal, Lindsey C. Beaulieu, Craig Kollman, Anne Adolph, Ashley H. Shoemaker, Risa Wolf, Georgeanna J. Klingensmith, William V. Tamborlane
Journal: Diabetes Care (2021)

Type 2 diabetes in the U.S. is more prevalent in youth of minority racial-ethnic background, but disparities in health outcomes have not been examined in this population.
Inherited human c-Rel deficiency disrupts myeloid and lymphoid immunity to multiple infectious agents
Authors: Romain Lévy, David Langlais, Vivien Béziat, Franck Rapaport, Geetha Rao, Tomi Lazarov, Mathieu Bourgey, Yu J. Zhou, Coralie Briand, Kunihiko Moriya, Fatima Ailal, Danielle T. Avery, Janet Markle, Ai Ing Lim, Masato Ogishi, Rui Yang, Simon Pelham, Mehdi Emam, Mélanie Migaud, Caroline Deswarte, Tanwir Habib, Luis R. Saraiva, Eman A. Moussa, Andrea Guennoun, Bertrand Boisson, Serkan Belkaya, Ruben Martinez-Barricarte, Jérémie Rosain, Aziz Belkadi, Sylvain Breton, Kathryn Payne, Ibtihal Benhsaien, Alessandro Plebani, Vassilios Lougaris, James P. Di Santo, Bénédicte Neven, Laurent Abel, Cindy S. Ma, Ahmed Aziz Bousfiha, Nico Marr, Jacinta Bustamante, Kang Liu, Philippe Gros, Frédéric Geissmann, Stuart G. Tangye, Jean-Laurent Casanova, Anne Puel
Journal: Journal of Clinical Investigation (2021)

We studied a child with severe viral, bacterial, fungal, and parasitic diseases, who was homozygous for a loss-of-function mutation of REL, encoding c-Rel, which is selectively expressed in lymphoid and myeloid cells. The patient had low frequencies of NK, effector memory cells reexpressing CD45RA (Temra) CD8+ T cells, memory CD4+ T cells, including Th1 and Th1*, Tregs, and memory B cells, whereas the counts and proportions of other leukocyte subsets were normal. Functional deficits of myeloid cells included the abolition of IL-12 and IL-23 production by conventional DC1s (cDC1s) and monocytes, but not cDC2s. c-Rel was also required for induction of CD86 expression on, and thus antigen-presenting cell function of, cDCs. Functional deficits of lymphoid cells included reduced IL-2 production by naive T cells, correlating with low proliferation and survival rates and poor production of Th1, Th2, and Th17 cytokines by memory CD4+ T cells. In naive CD4+ T cells, c-Rel is dispensable for early IL2 induction but contributes to later phases of IL2 expression. The patient's naive B cells displayed impaired MYC and BCL2L1 induction, compromising B cell survival and proliferation and preventing their differentiation into Ig-secreting plasmablasts. Inherited c-Rel deficiency disrupts the development and function of multiple myeloid and lymphoid cells, compromising innate and adaptive immunity to multiple infectious agents.
Neoadjuvant Endocrine Therapy in Clinical Practice
Authors: Tal Sella, Anna Weiss, Elizabeth A. Mittendorf, Tari A. King, Melissa Pilewskie, Armando E. Giuliano, Otto Metzger-Filho
Journal: JAMA Oncology (2021)

<h3>Importance</h3> In clinical practice, neoadjuvant endocrine therapy (NET) is rarely used despite being an effective treatment modality able to downstage tumors and facilitate breast-conserving surgery. <h3>Observations</h3> Using data from studies conducted since 2000, we provide readers with a critical in-depth review on clinical aspects related to the application of NET in the treatment of hormone receptor (HR)-positive/ERBB2 (formerly HER2)–negative breast cancer. This includes an overview of patient-selection criteria, regimen choice, treatment duration, evaluation of response by imaging, interpretation of pathology after treatment, and surgical considerations. Areas of controversy include the use of gene-expression tests for patient selection, treatment of premenopausal women, surgical management of the axilla after NET, and adjuvant systemic therapy decision-making, including the use of chemotherapy. <h3>Conclusions and Relevance</h3> NET is an optimal treatment modality for a considerable proportion of postmenopausal women diagnosed with HR-positive tumors. The treatment landscape for HR-positive breast cancer is evolving, with novel agents and the growing use of gene expression profiling to define treatment selection. As such, it is likely that NET use will increase and the practical considerations outlined here will become more important.
Association of Surgical Experience With Risk of Complication in Total Hip Arthroplasty Among Patients With Severe Obesity
Authors: Alexander Charalambous, Daniel Pincus, Sasha High, Fok-Han Leung, Suriya Aktar, J. Michael Paterson, Donald A. Redelmeier, Bheeshma Ravi
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Severe obesity is a risk factor for major early complications after total hip arthroplasty (THA). <h3>Objective</h3> To determine the association between surgeon experience with THA in patients with severe obesity and risk of complications. <h3>Design, Setting, and Participants</h3> This retrospective population-based cohort study was performed in Ontario, Canada, from April 1, 2007, to March 31, 2017, with data analysis performed from March 2020 to January 2021. A cohort of patients who received a primary THA for osteoarthritis and who also had severe obesity (body mass index [calculated as weight in kilograms divided by height in meters squared] ≥40) at the time of surgery was defined. These patients were identified using the Canadian Institute for Health Information Discharge Abstract Database and physician claims from the Ontario Health Insurance Plan. Generalized estimating equations were used to determine the association between overall THA and severe obesity–specific THA surgeon volume and the occurrence of complications after controlling for potential confounders. The study hypothesized that surgeon experience specific to patients with severe obesity could further reduce the risk of complications. <h3>Exposures</h3> Primary THA. <h3>Main Outcomes and Measures</h3> Complications were considered as a composite outcome (revision, infection requiring surgery, or dislocation requiring reduction), within 1 year of surgery. This was defined before the study, as was the study hypothesis. <h3>Results</h3> A total of 4781 eligible patients was identified. The median age was 63 (interquartile range [IQR], 56-69) years, and 3050 patients (63.8%) were women. Overall, 186 patients (3.9%) experienced a surgical complication within 1 year of surgery. The median overall THA surgeon volume was 70 (IQR, 46-106) cases/y, whereas the median obesity-specific surgeon volume was 5 (IQR, 2-9) cases/y. After controlling for patient and hospital factors, greater obesity-specific THA surgeon volume (adjusted odds ratio per additional 10 cases, 0.65 [95% CI, 0.47-0.89];<i>P</i> = .007), but not greater overall THA surgeon volume (adjusted odds ratio per 10 additional cases, 0.97 [95% CI, 0.93-1.02];<i>P</i> = .24), was associated with a reduced risk of complication. <h3>Conclusions and Relevance</h3> Increased surgeon experience performing THA in patients with severe obesity was associated with fewer major surgical complications. These findings suggest that surgeon experience is required to mitigate the unique anatomical challenges posed by surgery in patients with severe obesity. Referral pathways for patients with severe obesity to surgeons with high obesity-specific THA volume should be considered.