tbuckley/cabot-search huggingface dataset:
Effect of Bariatric Surgery on Risk of Complications After Total Knee Arthroplasty
Authors: Michelle M. Dowsey, Wendy A. Brown, Angela Cochrane, Paul R. Burton, Danny Liew, Peter F. Choong
Journal: JAMA Network Open (2022)

<h3>Importance</h3> People with severe obesity who undergo a total knee arthroplasty (TKA) for osteoarthritis (OA) are at higher risk of short-term and long-term complications compared with people with reference (&lt;30) body mass index (BMI; weight in kilograms divided by height in meters squared). It is not known whether weight loss before TKA modifies this risk. <h3>Objective</h3> To determine whether outcomes are improved by undergoing bariatric surgery before TKA in people with BMI greater than or equal to 35 and end-stage OA. <h3>Design, Setting, and Participants</h3> This parallel-group, assessor-blinded, randomized clinical trial was conducted between May 2012 and June 2020 with a minimum follow-up of 12 months after TKA. TKA was performed at a tertiary referral university-affiliated public hospital, and bariatric surgery was performed at a private hospital facility and a university-affiliated private practice. Data analysis was performed from February to July 2021. <h3>Interventions</h3> Bariatric surgery compared with usual weight management advice (treatment as usual [TAU]) in people scheduled for TKA. <h3>Main Outcomes and Measures</h3> The primary outcome was complications of TKA measured by a composite of death from any cause, perioperative or postoperative complications resulting in a discharge delay, unplanned procedure, or readmission for at least 12 months after TKA. Secondary outcomes included hospital bed day utilization, anthropomorphic measures, and patient-reported outcomes. <h3>Results</h3> Eighty-two patients waiting for TKA were randomized to undergo bariatric surgery (41 patients) or TAU (41 patients). Of the 82 participants, 66 (80.5%) were women, the mean (SD) age was 57.8 (4.9) years, and the mean (SD) BMI was 43.8 (5.5). Thirty-nine participants (95.1%) in the intervention group underwent laparoscopic adjustable gastric banding, and 29 (70.7%) subsequently underwent TKA. Thirty-nine patients (95.1%) in the TAU group underwent TKA. Six patients (14.6%) in the intervention group incurred the primary outcome (median follow-up, 24 months), compared with 15 (36.6%) in the TAU group (median follow-up, 27 months) (difference, 22.0%; 95% CI, 3.7% to 40.3%;<i>P</i> = .02). The between-group difference in BMI at 12 months was −6.32 (95% CI, −7.90 to −4.50;<i>P</i> &lt; .001) in favor of the intervention group. TKA was declined by 12 participants (29.3%) in the intervention group because of symptom improvement, whereas 2 participants (4.9%) in the TAU group declined TKA (difference, 24.4%; 95% CI, 9.0% to 39.8%;<i>P</i> = .003). <h3>Conclusions and Relevance</h3> Weight loss following bariatric surgery reduced the risk of complications of TKA in people with BMI greater than or equal to 35. Significantly fewer participants required TKA following weight loss, contributing to this finding. <h3>Trial Registration</h3> Australian New Zealand Clinical Trials Registry Number:ACTRN12611001178932
Dose- and Volume-Limiting Late Toxicity of FLASH Radiotherapy in Cats with Squamous Cell Carcinoma of the Nasal Planum and in Mini Pigs
Authors: Carla Rohrer Bley, Friederike Wolf, Patrik Gonçalves Jorge, Veljko Grilj, Ioannis Petridis, Benoit Petit, Till T. Böhlen, Raphael Moeckli, Charles Limoli, Jean Bourhis, Valeria Meier, Marie-Catherine Vozenin
Journal: Clinical Cancer Research (2022)

The FLASH effect is characterized by normal tissue sparing without compromising tumor control. Although demonstrated in various preclinical models, safe translation of FLASH-radiotherapy stands to benefit from larger vertebrate animal models. Based on prior results, we designed a randomized phase III trial to investigate the FLASH effect in cat patients with spontaneous tumors. In parallel, the sparing capacity of FLASH-radiotherapy was studied on mini pigs by using large field irradiation.
mbDenoise: microbiome data denoising using zero-inflated probabilistic principal components analysis
Authors: Yanyan Zeng, Jing Li, Chaochun Wei, Hongyu Zhao, Tao Wang
Journal: Genome biology (2022)

Abstract The analysis of microbiome data has several technical challenges. In particular, count matrices contain a large proportion of zeros, some of which are biological, whereas others are technical. Furthermore, the measurements suffer from unequal sequencing depth, overdispersion, and data redundancy. These nuisance factors introduce substantial noise. We propose an accurate and robust method, mbDenoise, for denoising microbiome data. Assuming a zero-inflated probabilistic PCA (ZIPPCA) model, mbDenoise uses variational approximation to learn the latent structure and recovers the true abundance levels using the posterior, borrowing information across samples and taxa. mbDenoise outperforms state-of-the-art methods to extract the signal for downstream analyses.
Mutant IDH Inhibits IFNγ–TET2 Signaling to Promote Immunoevasion and Tumor Maintenance in Cholangiocarcinoma
Authors: Meng-Ju Wu, Lei Shi, Juan Dubrot, Joshua Merritt, Vindhya Vijay, Ting-Yu Wei, Emily Kessler, Kira E. Olander, Ramzi Adil, Amaya Pankaj, Krishna Seshu Tummala, Vajira Weeresekara, Yuanli Zhen, Qibiao Wu, Meiqi Luo, William Shen, María García-Beccaria, Mirian Fernández-Vaquero, Christine Hudson, Sebastien Ronseaux, Yi Sun, Rodrigo Saad-Berreta, Russell W. Jenkins, Tong Wang, Mathias Heikenwälder, Cristina R. Ferrone, Lipika Goyal, Brandon Nicolay, Vikram Deshpande, Rahul M. Kohli, Hongwu Zheng, Robert T. Manguso, Nabeel Bardeesy
Journal: Cancer Discovery (2021)

Abstract Isocitrate dehydrogenase 1 mutations (mIDH1) are common in cholangiocarcinoma. (R)-2-hydroxyglutarate generated by the mIDH1 enzyme inhibits multiple α-ketoglutarate–dependent enzymes, altering epigenetics and metabolism. Here, by developing mIDH1-driven genetically engineered mouse models, we show that mIDH1 supports cholangiocarcinoma tumor maintenance through an immunoevasion program centered on dual (R)-2-hydroxyglutarate–mediated mechanisms: suppression of CD8+ T-cell activity and tumor cell–autonomous inactivation of TET2 DNA demethylase. Pharmacologic mIDH1 inhibition stimulates CD8+ T-cell recruitment and interferon γ (IFNγ) expression and promotes TET2-dependent induction of IFNγ response genes in tumor cells. CD8+ T-cell depletion or tumor cell–specific ablation of TET2 or IFNγ receptor 1 causes treatment resistance. Whereas immune-checkpoint activation limits mIDH1 inhibitor efficacy, CTLA4 blockade overcomes immunosuppression, providing therapeutic synergy. The findings in this mouse model of cholangiocarcinoma demonstrate that immune function and the IFNγ–TET2 axis are essential for response to mIDH1 inhibition and suggest a novel strategy for potentiating efficacy. Significance: Mutant IDH1 inhibition stimulates cytotoxic T-cell function and derepression of the DNA demethylating enzyme TET2, which is required for tumor cells to respond to IFNγ. The discovery of mechanisms of treatment efficacy and the identification of synergy by combined CTLA4 blockade provide the foundation for new therapeutic strategies. See related commentary by Zhu and Kwong, p. 604. This article is highlighted in the In This Issue feature, p. 587
Tisagenlecleucel in pediatric and young adult patients with Down syndrome-associated relapsed/refractory acute lymphoblastic leukemia
Authors: Theodore W. Laetsch, Shannon L. Maude, Adriana Balduzzi, Susana Rives, Henrique Bittencourt, Michael W. Boyer, Jochen Buechner, Barbara De Moerloose, Muna Qayed, Christine L. Phillips, Michael A. Pulsipher, Hidefumi Hiramatsu, Ranjan Tiwari, Stephan A. Grupp
Journal: Leukemia (2022)
Genome-wide risk prediction of common diseases across ancestries in one million people
Authors: Nina Mars, Sini Kerminen, Yen-Chen A. Feng, Masahiro Kanai, Kristi Läll, Laurent F. Thomas, Anne Heidi Skogholt, Pietro della Briotta Parolo, Benjamin M. Neale, Jordan W. Smoller, Maiken E. Gabrielsen, Kristian Hveem, Reedik Mägi, Koichi Matsuda, Yukinori Okada, Matti Pirinen, Aarno Palotie, Andrea Ganna, Alicia R. Martin, Samuli Ripatti
Journal: Cell Genomics (2022)

Polygenic risk scores (PRS) measure genetic disease susceptibility by combining risk effects across the genome. For coronary artery disease (CAD), type 2 diabetes (T2D), and breast and prostate cancer, we performed cross-ancestry evaluation of genome-wide PRSs in six biobanks in Europe, the United States, and Asia. We studied transferability of these highly polygenic, genome-wide PRSs across global ancestries, within European populations with different health-care systems, and local population substructures in a population isolate. All four PRSs had similar accuracy across European and Asian populations, with poorer transferability in the smaller group of individuals of African ancestry. The PRSs had highly similar effect sizes in different populations of European ancestry, and in early- and late-settlement regions with different recent population bottlenecks in Finland. Comparing genome-wide PRSs to PRSs containing a smaller number of variants, the highly polygenic, genome-wide PRSs generally displayed higher effect sizes and better transferability across global ancestries. Our findings indicate that in the populations investigated, the current genome-wide polygenic scores for common diseases have potential for clinical utility within different health-care settings for individuals of European ancestry, but that the utility in individuals of African ancestry is currently much lower.
Association of Treatment With Antipsychotics, Antidepressants, or Both With Movement Disorders and Seizures Among Children and Adolescents With Depression in Korea
Authors: Soo Min Jeon, Hae-Young Park, Susan Park, Un Sun Chung, Jin-Won Kwon
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Little evidence exists on neurological adverse events (movement disorders and seizures) that occur during adjuvant use of antipsychotics with antidepressants, especially in children and adolescents. <h3>Objective</h3> To assess the association between neurological adverse events (movement disorders, including parkinsonism, dystonia, extrapyramidal symptoms, chorea, and tic, and seizures) and the adjuvant use of antipsychotics in children and adolescents with depression. <h3>Design, Setting, and Participants</h3> A retrospective cohort study using the Health Insurance Review and Assessment claims database in Korea between 2008 and 2018. The study population was children and adolescents aged 2 to 18 years with depression who began treatment with antidepressants between January 1, 2010, and December 31, 2018. Data were analyzed between December 9, 2020, and December 10, 2021. <h3>Exposure</h3> Time-varying exposure to antidepressants, antipsychotics, and concomitant use of antidepressants and antipsychotics. Concomitant use was further subdivided according to the antipsychotic treatment status (dose and agent). <h3>Main Outcomes and Measures</h3> The extended Cox proportional hazards regression model, with adjustment for sex, age, health insurance type, psychiatric comorbidities, psychiatric hospitalization, and comedication with other psychotropic drugs, was used to estimate adjusted hazard ratios (aHRs) and 95% CIs for the associations of movement disorders and seizures with use of antidepressants and antipsychotics. <h3>Results</h3> A total of 9890 patients were included in the study: 9541 (mean [SD] age, 14.8 [2.8] years; 4956 [51.9%] female) and 7731 (mean [SD] age, 14.9 [2.7] years; 4150 [53.7%] female) met the inclusion criteria for movement disorders and seizures, respectively. For movement disorders, associations were found between concomitant use (aHR, 3.68; 95% CI, 3.06-4.44) and antipsychotic-only use (aHR, 3.84; 95% CI, 3.03-4.87) compared with antidepressant-only use, but their CIs overlapped. The associations with seizure were similar (concomitant use: aHR, 2.06; 95% CI, 1.66-2.55; antipsychotic-only use: aHR, 2.05; 95% CI, 1.53-2.75). With concomitant use, the aHRs gradually increased with increasing doses of antipsychotics. Haloperidol had the highest aHR, 7.15 (95% CI, 3.89-10.00) for movement disorders. The highest aHR for seizure was observed with quetiapine (aHR, 2.36; 95% CI, 1.55-3.59), followed by aripiprazole (aHR, 2.05; 95% CI, 1.52-2.77). <h3>Conclusions and Relevance</h3> In this cohort study, adjunctive antipsychotics with antidepressants were associated with movement disorders and seizures compared with antidepressant monotherapy in children and adolescents with depression. These results suggest that careful consideration of the risk-benefit profile of the antipsychotic use as adjuvant therapy in this population is needed.
Prognostic Value of Inflammatory Markers in Idiopathic Recurrent Pericarditis
Authors: Ashwin K. Kumar, Abdullah Yesilyaprak, Muhammad M. Furqan, Vardhmaan Jain, Bryce Montane, Massimo Imazio, Tom Kai Ming Wang, Christine L. Jellis, Paul C. Cremer, Allan L. Klein
Journal: Journal of the American College of Cardiology (2022)
Myoblast deactivation within engineered human skeletal muscle creates a transcriptionally heterogeneous population of quiescent satellite-like cells
Authors: Jason Wang, Torie Broer, Taylor Chavez, Chris J. Zhou, Sabrina Tran, Yu Xiang, Alastair Khodabukus, Yarui Diao, Nenad Bursac
Journal: Biomaterials (2022)
Can Breathing Pattern Assessment Predict the Need of Ventilatory Support in Treated Infants with Spinal Muscular Atrophy Type 1?
Authors: Antonella LoMauro, Chiara Mastella, Mariacristina Scoto, Francesco Muntoni, Elaine Chan, Lisa Edel, Andrea Aliverti, Giovanni Baranello
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

"Can Breathing Pattern Assessment Predict the Need of Ventilatory Support in Treated Infants with Spinal Muscular Atrophy Type 1?." American Journal of Respiratory and Critical Care Medicine, 206(1), pp. 118–120
Correction: Endoscopic resection of a large tongue-like esophageal mass: a rare case of esophageal striated muscle tumor
Authors: Zhenxiang Wang, Huihui Sun, Yu Zeng, Ying Chen, Jie Xiong, Ye Chen, Shuchang Xu
Journal: Endoscopy (2022)

Correction to: Endoscopic resection of a large tongue-like esophageal mass: a rare case of esophageal striated muscle tumorEndoscopy eFirstDOI: 10.1055/a-1730-4038
BNT162b2 mRNA COVID-19 vaccine and booster in patients with autoimmune rheumatic diseases: a national cohort study
Authors: Amir Bieber, Iftach Sagy, Lena Novack, Shay Brikman, Ran Abuhasira, Snait Ayalon, Irina Novofastovski, Mahmoud Abu-Shakra, Reuven Mader
Journal: Annals of the Rheumatic Diseases (2022)

Emerging evidence supports the immunogenic response to mRNA COVID-19 vaccine in patients with autoimmune rheumatic diseases (ARD). However, large-scale data about the association between vaccination, and COVID-19 outcomes in patients with ARD is limited.We used data from Clalit Health Services, which covers more than half of the population in Israel. Patients with ARD older than 18 were included between 20 December 2020 and 30 September 2021, when the BNT162b2 mRNA COVID-19 vaccine, and later a third booster dose, were available. The primary outcome was a documented positive SARS-CoV-2 PCR test. We used a Cox regression models with vaccination status as time-dependent covariate and calculated the HR for the study outcome.We included 127 928 patients with ARD, of whom, by the end of the study follow-up, there were 27 350 (21.3%) unvaccinated patients, 31 407 (24.5%) vaccinated patients and 69 171 (54.1%) patients who also received a third booster-dose. We identified 8470 (6.6%) patients with a positive SARS-CoV-2 PCR test during the study period. The HR for SARS-CoV-2 infection among the vaccination group was 0.143 (0.095 to 0.214, p<0.001), and among the booster group was 0.017 (0.009 to 0.035, p<0.001). Similar results were found regardless of the type of ARD group or antirheumatic therapy.Our results indicate that both the BNT162b2 mRNA COVID-19 vaccine and the booster are associated with better COVID-19 outcomes in patients with ARD.
Continuation of Bisphosphonate Therapy for Osteoporosis beyond 5 Years
Authors: Leslie L. Chang, Richard Eastell, Paul D. Miller
Journal: New England Journal of Medicine (2022)

This interactive feature about the use of bisphosphonates to treat osteoporosis offers a case vignette accompanied by two essays, one supporting continuation of bisphosphonate therapy beyond 5 years and the other supporting a “drug holiday.”
PD-L1–PD-1 interactions limit effector regulatory T cell populations at homeostasis and during infection
Authors: Joseph A. Perry, Lindsey Shallberg, Joseph T. Clark, Jodi A. Gullicksrud, Jonathan H. DeLong, Bonnie B. Douglas, Andrew P. Hart, Zachary Lanzar, Keenan O’Dea, Christoph Konradt, Jeongho Park, Juhi R. Kuchroo, Daniel Grubaugh, Arielle Glatman Zaretsky, Igor E. Brodsky, Rene de Waal Malefyt, David A. Christian, Arlene H. Sharpe, Christopher A. Hunter
Journal: Nature Immunology (2022)
Preclinical <i>In Vivo</i> Validation of the RAD51 Test for Identification of Homologous Recombination-Deficient Tumors and Patient Stratification
Authors: Benedetta Pellegrino, Andrea Herencia-Ropero, Alba Llop-Guevara, Flaminia Pedretti, Alejandro Moles-Fernández, Cristina Viaplana, Guillermo Villacampa, Marta Guzmán, Olga Rodríguez, Judit Grueso, Jose Jiménez, Enrique J. Arenas, Andrea Degasperi, João M.L. Dias, Josep V. Forment, Mark J. O'Connor, Olivier Déas, Stefano Cairo, Yinghui Zhou, Antonino Musolino, Carlos Caldas, Serena Nik-Zainal, Robert B. Clarke, Paolo Nuciforo, Orland Díez, Xavier Serres-Créixams, Vicente Peg, Martín Espinosa-Bravo, Teresa Macarulla, Ana Oaknin, Joaquin Mateo, Joaquín Arribas, Rodrigo Dienstmann, Meritxell Bellet, Mafalda Oliveira, Cristina Saura, Sara Gutiérrez-Enríquez, Judith Balmaña, Violeta Serra
Journal: Cancer Research (2022)

Abstract PARP inhibitors (PARPi) are approved drugs for platinum-sensitive, high-grade serous ovarian cancer (HGSOC) and for breast, prostate, and pancreatic cancers (PaC) harboring genetic alterations impairing homologous recombination repair (HRR). Detection of nuclear RAD51 foci in tumor cells is a marker of HRR functionality, and we previously established a test to detect RAD51 nuclear foci. Here, we aimed to validate the RAD51 score cut off and compare the performance of this test to other HRR deficiency (HRD) detection methods. Laboratory models from BRCA1/BRCA2-associated breast cancer, HGSOC, and PaC were developed and evaluated for their response to PARPi and cisplatin. HRD in these models and patient samples was evaluated by DNA sequencing of HRR genes, genomic HRD tests, and RAD51 foci detection. We established patient-derived xenograft models from breast cancer (n = 103), HGSOC (n = 4), and PaC (n = 2) that recapitulated patient HRD status and treatment response. The RAD51 test showed higher accuracy than HRR gene mutations and genomic HRD analysis for predicting PARPi response (95%, 67%, and 71%, respectively). RAD51 detection captured dynamic changes in HRR status upon acquisition of PARPi resistance. The accuracy of the RAD51 test was similar to HRR gene mutations for predicting platinum response. The predefined RAD51 score cut off was validated, and the high predictive value of the RAD51 test in preclinical models was confirmed. These results collectively support pursuing clinical assessment of the RAD51 test in patient samples from randomized trials testing PARPi or platinum-based therapies. Significance: This work demonstrates the high accuracy of a histopathology-based test based on the detection of RAD51 nuclear foci in predicting response to PARPi and cisplatin.
Deep Lipidomics in Human Plasma: Cardiometabolic Disease Risk and Effect of Dietary Fat Modulation
Authors: Fabian Eichelmann, Laury Sellem, Clemens Wittenbecher, Susanne Jäger, Olga Kuxhaus, Marcela Prada, Rafael Cuadrat, Kim G. Jackson, Julie A. Lovegrove, Matthias B. Schulze
Journal: Circulation (2022)

Background: In blood and tissues, dietary and endogenously generated fatty acids (FAs) occur in free form or as part of complex lipid molecules that collectively represent the lipidome of the respective tissue. We assessed associations of plasma lipids derived from high-resolution lipidomics with incident cardiometabolic diseases and subsequently tested if the identified risk-associated lipids were sensitive to dietary fat modification. Methods: The EPIC Potsdam cohort study (European Prospective Investigation into Cancer and Nutrition) comprises 27 548 participants recruited within an age range of 35 to 65 years from the general population around Potsdam, Germany. We generated 2 disease-specific case cohorts on the basis of a fixed random subsample (n=1262) and all respective cohort-wide identified incident primary cardiovascular disease (composite of fatal and nonfatal myocardial infarction and stroke; n=551) and type 2 diabetes (n=775) cases. We estimated the associations of baseline plasma concentrations of 282 class-specific FA abundances (calculated from 940 distinct molecular species across 15 lipid classes) with the outcomes in multivariable-adjusted Cox models. We tested the effect of an isoenergetic dietary fat modification on risk-associated lipids in the DIVAS randomized controlled trial (Dietary Intervention and Vascular Function; n=113). Participants consumed either a diet rich in saturated FAs (control), monounsaturated FAs, or a mixture of monounsaturated and n-6 polyunsaturated FAs for 16 weeks. Results: Sixty-nine lipids associated (false discovery rate&lt;0.05) with at least 1 outcome (both, 8; only cardiovascular disease, 49; only type 2 diabetes, 12). In brief, several monoacylglycerols and FA16:0 and FA18:0 in diacylglycerols were associated with both outcomes; cholesteryl esters, free fatty acids, and sphingolipids were largely cardiovascular disease specific; and several (glycero)phospholipids were type 2 diabetes specific. In addition, 19 risk-associated lipids were affected (false discovery rate&lt;0.05) by the diets rich in unsaturated dietary FAs compared with the saturated fat diet (17 in a direction consistent with a potential beneficial effect on long-term cardiometabolic risk). For example, the monounsaturated FA-rich diet decreased diacylglycerol(FA16:0) by 0.4 (95% CI, 0.5–0.3) SD units and increased triacylglycerol(FA22:1) by 0.5 (95% CI, 0.4–0.7) SD units. Conclusions: We identified several lipids associated with cardiometabolic disease risk. A subset was beneficially altered by a dietary fat intervention that supports the substitution of dietary saturated FAs with unsaturated FAs as a potential tool for primary disease prevention.
The gut environment regulates bacterial gene expression which modulates susceptibility to bacteriophage infection
Authors: Marta Lourenço, Lorenzo Chaffringeon, Quentin Lamy-Besnier, Marie Titécat, Thierry Pédron, Odile Sismeiro, Rachel Legendre, Hugo Varet, Jean-Yves Coppée, Marion Bérard, Luisa De Sordi, Laurent Debarbieux
Journal: Cell Host & Microbe (2022)
Thymidine starvation promotes c-di-AMP-dependent inflammation during pathogenic bacterial infection
Authors: Qing Tang, Mimi R. Precit, Maureen K. Thomason, Sophie F. Blanc, Fariha Ahmed-Qadri, Adelle P. McFarland, Daniel J. Wolter, Lucas R. Hoffman, Joshua J. Woodward
Journal: Cell Host & Microbe (2022)