tbuckley/cabot-search huggingface dataset:
First-in-human study of SBRT and adenosine pathway blockade to potentiate the benefit of immunochemotherapy in early-stage luminal B breast cancer: results of the safety run-in phase of the Neo-CheckRay trial
Authors: Alex De Caluwe, Emanuela Romano, Philip Poortmans, Andrea Gombos, Elisa Agostinetto, Guilherme Nader Marta, Zoe Denis, Stylianos Drisis, Christophe Vandekerkhove, Antoine Desmet, Catherine Philippson, Ligia Craciun, Isabelle Veys, Denis Larsimont, Marianne Paesmans, Dirk Van Gestel, Roberto Salgado, Christos Sotiriou, Martine Piccart-Gebhart, Michail Ignatiadis, Laurence Buisseret
Journal: Journal for ImmunoTherapy of Cancer (2023)

Luminal B breast cancer (BC) presents a worse prognosis when compared with luminal A BC and exhibits a lower sensitivity to chemotherapy and a lower immunogenicity in contrast to non-luminal BC subtypes. The Neo-CheckRay clinical trial investigates the use of stereotactic body radiation therapy (SBRT) directed to the primary tumor in combination with the adenosine pathway inhibitor oleclumab to improve the response to neo-adjuvant immuno-chemotherapy in luminal B BC. The trial consists of a safety run-in followed by a randomized phase II trial. Here, we present the results of the first-in-human safety run-in. The safety run-in was an open-label, single-arm trial in which six patients with early-stage luminal B BC received the following neo-adjuvant regimen: paclitaxel q1w×12 → doxorubicin/cyclophosphamide q2w×4; durvalumab (anti-programmed cell death receptor ligand 1 (PD-L1)) q4w×5; oleclumab (anti-CD73) q2w×4 → q4w×3 and 3×8 Gy SBRT to the primary tumor at week 5. Surgery must be performed 2-6 weeks after primary systemic treatment and adjuvant therapy was given per local guidelines, RT boost to the tumor bed was not allowed. Key inclusion criteria were: luminal BC, Ki67≥15% or histological grade 3, MammaPrint high risk, tumor size≥1.5 cm. Primary tumor tissue samples were collected at three timepoints: baseline, 1 week after SBRT and at surgery. Tumor-infiltrating lymphocytes, PD-L1 and CD73 were evaluated at each timepoint, and residual cancer burden (RCB) was calculated at surgery. Six patients were included between November 2019 and March 2020. Median age was 53 years, range 37-69. All patients received SBRT and underwent surgery 2-4 weeks after the last treatment. After a median follow-up time of 2 years after surgery, one grade 3 adverse event (AE) was reported: pericarditis with rapid resolution under corticosteroids. No grade 4-5 AE were documented. Overall cosmetical breast evaluation after surgery was 'excellent' in four patients and 'good' in two patients. RCB results were 2/6 RCB 0; 2/6 RCB 1; 1/6 RCB 2 and 1/6 RCB 3. This novel treatment combination was considered safe and is worth further investigation in a randomized phase II trial. NCT03875573.
A reproducible signature of cytoskeletal and ALS-related genes in human motoneurons
Authors: Archana Yadav, Kaya J.E. Matson, Dylan Lee, Mor R. Alkaslasi, R. Brian Roome, Michael E. Ward, Hemali Phatnani, Claire E. Le Pichon, Vilas Menon, Ariel J. Levine
Journal: Neuron (2023)
Physical activity behaviors in trans and gender diverse adults: a scoping review
Authors: Kai Schweizer, Felicity Austin, Kemi E. Wright, Ashleigh Lin, Xander Bickendorf, Ben Jackson, Penelope Strauss, Hunter Gurevich, Christine Granger, Jessica Luke, Bonnie J. Furzer
Journal: International Journal of Transgender Health (2023)

Background : There is currently limited data regarding the physical activity behaviors of trans and gender diverse people (including binary and non-binary identities; henceforth trans). The aim of this review was to synthesize the existing literature in this area, with a focus on physical activity behaviors as they relate to health (e.g. health benefits, risks of adverse health outcomes). Methods : A scoping review protocol was used to search Medline, Scopus, ProQuest, and CINAHL in order to identify qualitative and quantitative articles, published as of September 2023, that reported physical activity behaviors in trans adults. Quality assessments were conducted based on standard criteria. Results : Twenty-four articles were included in the final analysis, with methodological quality ranging from 0.45 to 0.95 on a scale ranging from 0.0 (low quality) to 1.0 (high quality). Five articles reported low levels of physical activity compared to global health recommendations and one article reported physical activity exceeding the minimum recommendation. Nine articles reported lower levels of physical activity in trans people compared to cisgender people, whereas two reported similar levels of physical activity and one reported higher levels in trans people. A total of 12 different measures were used to assess physical activity levels, of which only seven were validated measures. Seven articles reported compulsive exercise in trans people and five articles reported physical health risks in a sample of trans people with low physical activity levels. Five articles reported physical activity levels influenced by gender congruence or body satisfaction. Six articles reported physical activity influenced by minority stress, experienced discrimination, or anticipated discrimination. Discussion : This review highlights the need for further research regarding the physical activity behaviors of trans individuals, especially with regard to the impact on health (e.g. excessive, or insufficient levels of activity) and consideration of consistency of physical activity measures and reporting. The findings suggest a need to consider the unique influences on physical activity participation in this population when providing services and/or promoting physical activity in support of health.
Global Streptococcus pyogenes strain diversity, disease associations, and implications for vaccine development: a systematic review
Authors: Pierre R Smeesters, Gabrielle de Crombrugghe, Shu Ki Tsoi, Céline Leclercq, Ciara Baker, Joshua Osowicki, Caroline Verhoeven, Anne Botteaux, Andrew C Steer
Journal: The Lancet Microbe (2023)

The high strain diversity of Streptococcus pyogenes serves as a major obstacle to vaccine development against this leading global pathogen. We did a systematic review of studies in PubMed, MEDLINE, and Embase that reported the global distribution of S pyogenes emm-types and emm-clusters from Jan 1, 1990, to Feb 23, 2023. 212 datasets were included from 55 countries, encompassing 74 468 bacterial isolates belonging to 211 emm-types. Globally, an inverse correlation was observed between strain diversity and the UNDP Human Development Index (HDI; r=−0·72; p<0·0001), which remained consistent upon subanalysis by global region and site of infection. Greater strain diversity was associated with a lower HDI, suggesting the role of social determinants in diseases caused by S pyogenes. We used a population-weighted analysis to adjust for the disproportionate number of epidemiological studies from high-income countries and identified 15 key representative isolates as vaccine targets. Strong strain type associations were observed between the site of infection (invasive, skin, and throat) and several streptococcal lineages. In conclusion, the development of a truly global vaccine to reduce the immense burden of diseases caused by S pyogenes should consider the multidimensional diversity of the pathogen, including its social and environmental context, and not merely its geographical distribution.
Maternal morbidity: the lifelong experience of survivors
Authors: Sayeba Akhter
Journal: The Lancet Global Health (2023)

The Series on maternal health in the perinatal period and beyond explores the effects of traumatic childbirth on women's health and wellbeing, with particular attention to its medium-term and long-term consequences. I found some of the concepts very interesting and thought-provoking. Efforts to reduce maternal mortality consume all resources, so morbidity issues never gain priority. From my experience, I agree that the conventional assignment of the first 6 weeks of the postnatal period as the puerperium narrows the clinical focus to the immediate consequences of childbirth, and the delayed effects are often neglected.
Maternal health in a dramatically different world: tailoring actions to achieve targets for 2030 and beyond
Authors: Olufemi T Oladapo, Åsa Nihlén
Journal: The Lancet Global Health (2023)

The global community failed to fulfil its promise to attain the millennium development goal (MDG) target for maternal mortality and is currently not on track to achieve the sustainable development goal (SDG) target by 2030. The latest maternal mortality estimates, covering 2000 to 2020, show little or no meaningful progress in maternal mortality reduction during the last decade of the report.1 This unusally slow progress might be related to the use of the same strategies applied during the MDG era to address maternal health problems in a world that has drastically and fundamentally changed since the adoption of the 2030 sustainable development agenda.
A core outcome set for bronchiectasis in children and adolescents for use in clinical research: an international consensus study
Authors: Anne B Chang, Jeanette Boyd, Andrew Bush, Adam T Hill, Zena Powell, Angela Zacharasiewicz, Efthymia Alexopoulou, Andrew J Collaro, James D Chalmers, Carolina Constant, Konstantinos Douros, Rebecca Fortescue, Matthias Griese, Jonathan Grigg, Andreas Hector, Bulent Karadag, Oleksandr Mazulov, Fabio Midulla, Alexander Moeller, Marijke Proesmans, Christine Wilson, Stephanie T Yerkovich, Ahmad Kantar, Keith Grimwood
Journal: The Lancet Respiratory Medicine (2023)
MYSM1 attenuates DNA damage signals triggered by physiologic and genotoxic DNA breaks
Authors: Brendan Mathias, David O’Leary, Nermina Saucier, Faiz Ahmad, Lynn S. White, Le’Mark Russell, Marwan Shinawi, Matthew J. Smith, Roshini S. Abraham, Megan A. Cooper, Maleewan Kitcharoensakkul, Abby M. Green, Jeffrey J. Bednarski
Journal: Journal of Allergy and Clinical Immunology (2023)

Patients with deleterious variants in MYSM1 have an immune deficiency characterized by B-cell lymphopenia, hypogammaglobulinemia, and increased radiosensitivity. MYSM1 is a histone deubiquitinase with established activity in regulating gene expression. MYSM1 also localizes to sites of DNA injury but its function in cellular responses to DNA breaks has not been elucidated.
Overcoming Resistance in Chronic Lymphocytic Leukemia—Maybe Less Is More?
Authors: Othman Al-Sawaf, Matthew S. Davids
Journal: Clinical Cancer Research (2023)

Abstract Acquired mutations in BTK, PLCG2, and BCL2 are associated with resistance to continuous targeted agent therapy in chronic lymphocytic leukemia (CLL). Here, we discuss new evidence that limiting the duration of CLL therapy may prevent the evolution of such resistance mutations, potentially facilitating effective retreatment strategies. See related article by Jain et al., p. 498
Baricitinib and β-Cell Function in Patients with New-Onset Type 1 Diabetes
Authors: Michaela Waibel, John M. Wentworth, Michelle So, Jennifer J. Couper, Fergus J. Cameron, Richard J. MacIsaac, Gabby Atlas, Alexandra Gorelik, Sara Litwak, Laura Sanz-Villanueva, Prerak Trivedi, Simi Ahmed, Francis J. Martin, Madeleine E. Doyle, Jessica E. Harbison, Candice Hall, Balasubramanian Krishnamurthy, Peter G. Colman, Leonard C. Harrison, Helen E. Thomas, Thomas W.H. Kay
Journal: New England Journal of Medicine (2023)

Janus kinase (JAK) inhibitors, including baricitinib, block cytokine signaling and are effective disease-modifying treatments for several autoimmune diseases. Whether baricitinib preserves β-cell function in type 1 diabetes is unclear.In this phase 2, double-blind, randomized, placebo-controlled trial, we assigned patients with type 1 diabetes diagnosed during the previous 100 days to receive baricitinib (4 mg once per day) or matched placebo orally for 48 weeks. The primary outcome was the mean C-peptide level, determined from the area under the concentration-time curve, during a 2-hour mixed-meal tolerance test at week 48. Secondary outcomes included the change from baseline in the glycated hemoglobin level, the daily insulin dose, and measures of glycemic control assessed with the use of continuous glucose monitoring.A total of 91 patients received baricitinib (60 patients) or placebo (31 patients). The median of the mixed-meal-stimulated mean C-peptide level at week 48 was 0.65 nmol per liter per minute (interquartile range, 0.31 to 0.82) in the baricitinib group and 0.43 nmol per liter per minute (interquartile range, 0.13 to 0.63) in the placebo group (P = 0.001). The mean daily insulin dose at 48 weeks was 0.41 U per kilogram of body weight per day (95% confidence interval [CI], 0.35 to 0.48) in the baricitinib group and 0.52 U per kilogram per day (95% CI, 0.44 to 0.60) in the placebo group. The levels of glycated hemoglobin were similar in the two trial groups. However, the mean coefficient of variation of the glucose level at 48 weeks, as measured by continuous glucose monitoring, was 29.6% (95% CI, 27.8 to 31.3) in the baricitinib group and 33.8% (95% CI, 31.5 to 36.2) in the placebo group. The frequency and severity of adverse events were similar in the two trial groups, and no serious adverse events were attributed to baricitinib or placebo.In patients with type 1 diabetes of recent onset, daily treatment with baricitinib over 48 weeks appeared to preserve β-cell function as estimated by the mixed-meal-stimulated mean C-peptide level. (Funded by JDRF International and others; BANDIT Australian New Zealand Clinical Trials Registry number, ACTRN12620000239965.).
Mirvetuximab Soravtansine in FRα-Positive, Platinum-Resistant Ovarian Cancer
Authors: Kathleen N. Moore, Antoine Angelergues, Gottfried E. Konecny, Yolanda García, Susana Banerjee, Domenica Lorusso, Jung-Yun Lee, John W. Moroney, Nicoletta Colombo, Andrzej Roszak, Jacqueline Tromp, Tashanna Myers, Jeong-Won Lee, Mario Beiner, Casey M. Cosgrove, David Cibula, Lainie P. Martin, Renaud Sabatier, Joseph Buscema, Purificación Estévez-García, Lan Coffman, Shibani Nicum, Linda R. Duska, Sandro Pignata, Fernando Gálvez, Yuemei Wang, Michael Method, Anna Berkenblit, Diana Bello Roufai, Toon Van Gorp
Journal: New England Journal of Medicine (2023)

Mirvetuximab soravtansine-gynx (MIRV), a first-in-class antibody-drug conjugate targeting folate receptor α (FRα), is approved for the treatment of platinum-resistant ovarian cancer in the United States.We conducted a phase 3, global, confirmatory, open-label, randomized, controlled trial to compare the efficacy and safety of MIRV with the investigator's choice of chemotherapy in the treatment of platinum-resistant, high-grade serous ovarian cancer. Participants who had previously received one to three lines of therapy and had high FRα tumor expression (≥75% of cells with ≥2+ staining intensity) were randomly assigned in a 1:1 ratio to receive MIRV (6 mg per kilogram of adjusted ideal body weight every 3 weeks) or chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan). The primary end point was investigator-assessed progression-free survival; key secondary analytic end points included objective response, overall survival, and participant-reported outcomes.A total of 453 participants underwent randomization; 227 were assigned to the MIRV group and 226 to the chemotherapy group. The median progression-free survival was 5.62 months (95% confidence interval [CI], 4.34 to 5.95) with MIRV and 3.98 months (95% CI, 2.86 to 4.47) with chemotherapy (P<0.001). An objective response occurred in 42.3% of the participants in the MIRV group and in 15.9% of those in the chemotherapy group (odds ratio, 3.81; 95% CI, 2.44 to 5.94; P<0.001). Overall survival was significantly longer with MIRV than with chemotherapy (median, 16.46 months vs. 12.75 months; hazard ratio for death, 0.67; 95% CI, 0.50 to 0.89; P = 0.005). During the treatment period, fewer adverse events of grade 3 or higher occurred with MIRV than with chemotherapy (41.7% vs. 54.1%), as did serious adverse events of any grade (23.9% vs. 32.9%) and events leading to discontinuation (9.2% vs. 15.9%).Among participants with platinum-resistant, FRα-positive ovarian cancer, treatment with MIRV showed a significant benefit over chemotherapy with respect to progression-free and overall survival and objective response. (Funded by ImmunoGen; MIRASOL ClinicalTrials.gov number, NCT04209855.).
Immune Interventions at Onset of Type 1 Diabetes — Finally, a Bit of Hope
Authors: Johnny Ludvigsson
Journal: New England Journal of Medicine (2023)

Huge improvements in the treatment of many serious diseases have been made in the past half century, during which I have had the privilege of working first as a pediatric oncologist and later as a diabetologist. In the field of pediatric oncology, scientific progress has dramatically changed the prognosis for many forms of cancer from very high mortality to a cure for most children who are affected. Furthermore, effective therapy for other disabling diseases such as juvenile idiopathic arthritis now exists, and severe symptoms of childhood asthma are rare, owing to advances in care. The list goes on. In contrast, . . .
Small Airway Disease in Pre-Chronic Obstructive Pulmonary Disease with Emphysema: A Cross-Sectional Study
Authors: Stijn E. Verleden, Jeroen M. H. Hendriks, Annemiek Snoeckx, Cindy Mai, Yves Mentens, Wim Callebaut, Bruno De Belie, Paul E. Van Schil, Veronique Verplancke, Annelies Janssens, Joseph Jacob, Ashkan Pakzad, Thomas M. Conlon, Guney Guvenc, Ali Önder Yildirim, Patrick Pauwels, Senada Koljenovic, Johanna M. Kwakkel-Van Erp, Thérèse S. Lapperre
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Small airway disease is an important pathophysiological feature of chronic obstructive pulmonary disease (COPD). Recently, "pre-COPD" has been put forward as a potential precursor stage of COPD that is defined by abnormal spirometry findings or significant emphysema on computed tomography (CT) in the absence of airflow obstruction.
A Look at Surgical Care in a State Correctional System—Unique and Informative but Incomplete
Authors: Michaela A. West
Journal: JAMA Surgery (2023)

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
Even Mild Lack of Sleep Might Raise Women’s Diabetes Risk
Authors: Emily Harris
Journal: JAMA (2023)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Measuring Outcomes in the Treatment of Obesity
Authors: Megan Jenkins, Marina Kurian, Rachel Moore
Journal: JAMA Surgery (2023)

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