tbuckley/cabot-search huggingface dataset:
Lack of gut microbiome recovery with spinal cord injury rehabilitation
Authors: Ayelet Gur Arie, Itamar Toren, Rotem Hadar, Tzipi Braun, Gilat Efroni, Efrat Glick Saar, Zecharia Madar, Amnon Amir, Gabriel Zeilig, Yael Haberman
Journal: Gut Microbes (2024)

Spinal cord injury (SCI) is a devastating event that significantly changes daily function and quality of life and is linked to bowel and bladder dysfunction and frequent antibiotic treatment. We aimed to study the composition of the gut microbiome in individuals with SCI during the initial sub-acute rehabilitation process and during the chronic phase of the injury. This study included 100 fecal samples from 63 participants (Median age 40 years, 94% males): 13 cases with SCI in the sub-acute phase with 50 longitudinal samples, 18 cases with chronic SCI, and 32 age and gender-matched controls. We show, using complementary methods, that the time from the injury was a dominant factor linked with gut microbiome composition. Surprisingly, we demonstrated a lack of gut microbial recovery during rehabilitation during the sub-acute phase, with further deviation from the non-SCI control group in the chronic ambulatory SCI group. To generalize the results, we were able to show significant similarity of the signal when comparing to a previous cohort with SCI, to subjects from the American Gut Project who reported low physical activity, and to subjects from another population-based cohort who reported less normal stool consistency. Restoration of the microbiome composition may be another desirable measure for SCI recovery in the future, but further research is needed to test whether such restoration is associated with improved neurological outcomes and quality of life.
Brain-derived autophagosome profiling reveals the engulfment of nucleoid-enriched mitochondrial fragments by basal autophagy in neurons
Authors: Juliet Goldsmith, Alban Ordureau, J. Wade Harper, Erika L.F. Holzbaur
Journal: Neuron (2024)

(Neuron 110, 967–976.e1–e8; March 16, 2022) In our published paper, we determined a median cargo score of 0.0331, as shown in Figures 1D, 2A, 2G, and 3A, and all analysis was performed using this median value. However, there is a typographical error in the first paragraph of the section entitled “Proteomics identify cargos of basal autophagy in the brain,” in which the median score was mistakenly written as 0.331, which should read 0.0331. Importantly, no results or conclusions are altered by this typographical correction. Brain-derived autophagosome profiling reveals the engulfment of nucleoid-enriched mitochondrial fragments by basal autophagy in neuronsGoldsmith et al.NeuronJanuary 19, 2022In BriefAutophagy is a conserved pathway for the degradation of aggregated proteins and dysfunctional organelles that is required for neuronal homeostasis. Goldsmith et al. perform proteomic profiling of cargos degraded by autophagy in brain and neurons under basal conditions, identifying the turnover of mitochondrial nucleoids as a primary function of neuronal autophagy. Full-Text PDF Open Archive
M2 macrophages secrete glutamate-containing extracellular vesicles to alleviate osteoporosis by reshaping osteoclast precursor fate
Authors: Xiaoyuan Huang, Yanhua Lan, Jiahui Shen, Xiaomin Zhao, Yanyan Zhou, Wenzhi Wu, Jiajie Mao, Yuzhu Wu, Zhijian Xie, Zhuo Chen
Journal: Molecular Therapy (2024)

Osteoclast precursors (OCPs) are thought to commit to osteoclast differentiation, which is accelerated by aging-related chronic inflammation, thereby leading to osteoporosis. However, whether the fate of OCPs can be reshaped to transition into other cell lineages is unknown. Here, we showed that M2 macrophage-derived extracellular vesicles (M2-EVs) could reprogram OCPs to downregulate osteoclast-specific gene expression and convert OCPs to M2 macrophage-like lineage cells, which reshaped the fate of OCPs by delivering the molecular metabolite glutamate. Upon delivery of glutamate, glutamine metabolism in OCPs was markedly enhanced, resulting in the increased production of α-ketoglutarate (αKG), which participates in Jmjd3-dependent epigenetic reprogramming, causing M2-like macrophage differentiation. Thus, we revealed a novel transformation of OCPs into M2-like macrophages via M2-EVs-initiated metabolic reprogramming and epigenetic modification. Our findings suggest that M2-EVs can reestablish the balance between osteoclasts and M2 macrophages, alleviate the symptoms of bone loss, and constitute a new approach for bone-targeted therapy to treat osteoporosis. Osteoclast precursors (OCPs) are thought to commit to osteoclast differentiation, which is accelerated by aging-related chronic inflammation, thereby leading to osteoporosis. However, whether the fate of OCPs can be reshaped to transition into other cell lineages is unknown. Here, we showed that M2 macrophage-derived extracellular vesicles (M2-EVs) could reprogram OCPs to downregulate osteoclast-specific gene expression and convert OCPs to M2 macrophage-like lineage cells, which reshaped the fate of OCPs by delivering the molecular metabolite glutamate. Upon delivery of glutamate, glutamine metabolism in OCPs was markedly enhanced, resulting in the increased production of α-ketoglutarate (αKG), which participates in Jmjd3-dependent epigenetic reprogramming, causing M2-like macrophage differentiation. Thus, we revealed a novel transformation of OCPs into M2-like macrophages via M2-EVs-initiated metabolic reprogramming and epigenetic modification. Our findings suggest that M2-EVs can reestablish the balance between osteoclasts and M2 macrophages, alleviate the symptoms of bone loss, and constitute a new approach for bone-targeted therapy to treat osteoporosis.
Thrombectomy in Medium to Large Ischemic Core
Authors: Umberto Pensato, Ronda Lun, Andrew Demchuk
Journal: JAMA (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 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
Major HBV splice variant encoding a novel protein important for infection
Authors: Chen-Yen Chung, Cheng-Pu Sun, Mi-Hua Tao, Hui-Lin Wu, Sheng-Han Wang, Shiou-Hwei Yeh, Qing-Bing Zheng, Quan Yuan, Ning-Shao Xia, Kenji Ogawa, Kenji Nakashima, Tetsuro Suzuki, Pei-Jer Chen
Journal: Journal of Hepatology (2024)
Trends in Obstetrics and Gynecology Residency Applications in the Year After Abortion Access Changes
Authors: Maya M. Hammoud, Helen K. Morgan, Karen George, Arthur T. Ollendorff, John L. Dalrymple, Dana Dunleavy, Min Zhu, Erika Banks, Bukky Ajagbe Akingbola, AnnaMarie Connolly
Journal: JAMA Network Open (2024)

Importance State-specific abortion restrictions currently affect the training of approximately 44% of obstetrics and gynecology (OBGYN) residents in the US. Examination of where future trainees apply for residency is important. Objective To assess changes in the percentage of applicants to OBGYN residency programs by state based on abortion restrictions in place after the Dobbs v Jackson Women’s Health Organization (hereafter, Dobbs v Jackson ) US Supreme Court decision and examine whether applicants’ preference for programs, as suggested by the distribution of application signals that express higher interest, was associated with abortion bans. Design, Setting, and Participants This serial cross-sectional study used anonymized data for all applicants to OBGYN residency programs in the US during September and October from 2019 to 2023. Data were obtained from the Association of American Medical Colleges Electronic Residency Application Service. Exposures Applications and program preference signals sent to OBGYN residency programs, analyzed by applicants’ self-reported demographics. Main Outcomes and Measures The primary outcome was differences in the percentage of unique applicants to OBGYN residency programs from 2019 to 2023, with programs categorized by state-based abortion restrictions after the Dobbs v Jackson decision. Secondary outcomes included the distribution of program signals by state abortion ban status. Results A total of 2463 applicants (2104 [85.4%] women) who applied to OBGYN programs for the 2023 residency match cycle were the focal sample of this study. While overall applicant numbers remained stable between 2019 and 2023, the number of applicants differed significantly by state abortion ban status in the 2022 ( F 2,1087 = 10.82; P &amp;amp;lt; .001) and the 2023 ( F 2,1087 = 14.31; P &amp;amp;lt; .001) match cycles. There were no differences in the number of signals received by programs in states with bans after controlling for known covariates such as number of applications received and program size, and there were no differences in the percentage of signals sent by out-of-state applicants to programs in states with different abortion laws than their home states ( F 2,268 = 2.41; P = .09). Conclusions and Relevance In this cross-sectional study, there was a small but statistically significant decrease in the number of applicants to OBGYN residency programs in states with abortion bans in 2023 compared with 2022. However, applicant signaling data did not vary by states’ abortion ban status. While OBGYN residency programs almost completely filled in 2023, continued monitoring for the potential consequences of state abortion bans for OBGYN training is needed.
Machine Learning Models for Predicting Disability and Pain Following Lumbar Disc Herniation Surgery
Authors: Bjørnar Berg, Martin A. Gorosito, Olaf Fjeld, Hårek Haugerud, Kjersti Storheim, Tore K. Solberg, Margreth Grotle
Journal: JAMA Network Open (2024)

Importance Lumber disc herniation surgery can reduce pain and disability. However, a sizable minority of individuals experience minimal benefit, necessitating the development of accurate prediction models. Objective To develop and validate prediction models for disability and pain 12 months after lumbar disc herniation surgery. Design, Setting, and Participants A prospective, multicenter, registry-based prognostic study was conducted on a cohort of individuals undergoing lumbar disc herniation surgery from January 1, 2007, to May 31, 2021. Patients in the Norwegian Registry for Spine Surgery from all public and private hospitals in Norway performing spine surgery were included. Data analysis was performed from January to June 2023. Exposures Microdiscectomy or open discectomy. Main Outcomes and Measures Treatment success at 12 months, defined as improvement in Oswestry Disability Index (ODI) of 22 points or more; Numeric Rating Scale (NRS) back pain improvement of 2 or more points, and NRS leg pain improvement of 4 or more points. Machine learning models were trained for model development and internal-external cross-validation applied over geographic regions to validate the models. Model performance was assessed through discrimination ( C statistic) and calibration (slope and intercept). Results Analysis included 22 707 surgical cases (21 161 patients) (ODI model) (mean [SD] age, 47.0 [14.0] years; 12 952 [57.0%] males). Treatment nonsuccess was experienced by 33% (ODI), 27% (NRS back pain), and 31% (NRS leg pain) of the patients. In internal-external cross-validation, the selected machine learning models showed consistent discrimination and calibration across all 5 regions. The C statistic ranged from 0.81 to 0.84 (pooled random-effects meta-analysis estimate, 0.82; 95% CI, 0.81-0.84) for the ODI model. Calibration slopes (point estimates, 0.94-1.03; pooled estimate, 0.99; 95% CI, 0.93-1.06) and calibration intercepts (point estimates, −0.05 to 0.11; pooled estimate, 0.01; 95% CI, −0.07 to 0.10) were also consistent across regions. For NRS back pain, the C statistic ranged from 0.75 to 0.80 (pooled estimate, 0.77; 95% CI, 0.75-0.79); for NRS leg pain, the C statistic ranged from 0.74 to 0.77 (pooled estimate, 0.75; 95% CI, 0.74-0.76). Only minor heterogeneity was found in calibration slopes and intercepts. Conclusion The findings of this study suggest that the models developed can inform patients and clinicians about individual prognosis and aid in surgical decision-making.
Anticoagulation for Atrial Cardiopathy in Cryptogenic Stroke
Authors: Gregory M. Marcus, Bruce Ovbiagele
Journal: JAMA (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 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
FDA Approval Summary: Lisocabtagene Maraleucel for Second-Line Treatment of Large B-Cell Lymphoma
Authors: Mona Elmacken, Helkha Peredo-Pinto, Cong Wang, Zhenzhen Xu, Million Tegenge, Adnan A. Jaigirdar, Marc R. Theoret, Tejashri Purohit-Sheth, Yvette L. Kasamon
Journal: Clinical Cancer Research (2024)

In June 2022, the FDA extended the indication for lisocabtagene maraleucel (liso-cel) to include adults with large B-cell lymphoma (LBCL) who have refractory disease or relapse within 12 months of first-line chemoimmunotherapy (CIT), as well as transplant-ineligible adults with refractory disease or relapse after first-line CIT. Two clinical trials evaluating a single infusion of liso-cel preceded by lymphodepleting chemotherapy supported the second-line indications. TRANSFORM is a randomized, phase 3, open-label trial comparing liso-cel with standard second-line therapy, including planned autologous hematopoietic stem cell transplantation (HSCT), in 184 transplant-eligible patients. On interim analysis, event-free survival (EFS) by independent review committee (IRC) assessment was statistically significantly improved for the liso-cel arm, with a stratified hazard ratio of 0.34 [95% confidence interval (CI), 0.22-0.51; P < 0.0001]; the estimated median EFS was 10.1 months in the liso-cel arm versus 2.3 months in the control arm. PILOT is a single-arm phase 2 trial of second-line liso-cel in patients who were transplant-ineligible due to age or comorbidities but had adequate organ function for chimeric antigen receptor (CAR) T-cell therapy. Among 61 patients who received liso-cel (median age, 74 years), the IRC-assessed complete response rate was 54% (95% CI, 41-67). Among patients achieving complete response, the estimated 1-year rate of continued response was 68% (95% CI, 45-83). Of the 268 patients combined who received liso-cel as second-line therapy for LBCL, cytokine release syndrome occurred in 45% (Grade 3, 1.3%) and CAR T-cell-associated neurologic toxicities occurred in 27% (Grade 3, 7%), warranting a continued risk evaluation and mitigation strategy.
Single versus multiple arterial coronary artery bypass grafting in men and women: Results from Polish National Registry of Cardiac Surgery Procedures
Authors: Sleiman Sebastian Aboul-Hassan, Grzegorz Hirnle, Bartlomiej Perek, Marek Jemielity, Tomasz Hirnle, Miroslaw Brykczynski, Marek Deja, Jan Rogowski, Marek Cisowski, Michal Krejca, Lech Anisimowicz, Kazimierz Widenka, Witold Gerber, Jerzy Pacholewicz, Pawel Bugajski, Piotr Stepinski, Bohdan J Maruszewski, Romuald Cichon, Tomasz Hrapkowicz
Journal: International Journal of Surgery (2024)

Background: The objective of this multicenter study aimed to investigate the impact of sex on long-term survival among patients with multivessel coronary artery disease undergoing coronary artery bypass grafting(CABG) using multiple arterial grafting (MAG) or a single artery with saphenous vein grafts (SAG). Materials and methods: Data were obtained from the Polish National Registry of Cardiac Surgery Procedures database. This study included 81,136 patients who underwent CABG for multivessel disease between January 2012 and December 2020 (22.9% were women and 77.1% were men). MAG was performed in 8.3% and 11.7% of female and male patients, respectively. A 1:1 propensity score (PS)-matching was performed. Long-term mortality was compared between matched groups of men and women. Subgroup analyses of patients aged &lt;70 and ≥70 years, with an ejection fraction (EF) &gt;40% and ≤40%, and with and without diabetes, obesity, peripheral artery disease (PAD), or chronic lung disease (CLD) were performed separately in women and men. Results: MAG was associated with lower long-term mortality than SAG in 1,528 PS-matched female pairs (hazard ratio [HR]: 0.74; 95% confidence interval [CI]: 0.59–0.92; P = 0.007) and 7,283 PS-matched male pairs (HR: 0.80; 95% CI: 0.72–0.88; P &lt;0.001). Subgroup analyses confirmed the results among female patients aged &lt;70 years, with diabetes and EF &gt;40%, and without PAD or CLD, and of male patients aged &lt;70 and ≥70 years; with EF &gt;40%; with or without diabetes, obesity, or PAD; and without CLD. Conclusions: In patients undergoing CABG, MAG was associated with significantly improved survival in both sexes. The long-term benefits of MAG observed across subgroups of men and women support the consideration of a multi-arterial revascularization strategy for a broader spectrum of patients.
β-Blocker Withdrawal and Functional Capacity Improvement in Patients With Heart Failure With Preserved Ejection Fraction
Authors: Patricia Palau, Rafael de la Espriella, Julia Seller, Enrique Santas, Eloy Domínguez, Vicent Bodí, Juan Sanchis, Eduardo Núñez, Antoni Bayés-Genís, Vicente Bertomeu-González, Markus Meyer, Julio Núñez
Journal: JAMA Cardiology (2024)

Increasing the patient's heart rate (HR) has emerged as a therapeutic option in patients with heart failure with preserved ejection fraction (HFpEF). However, the evidence is conflicting, and the profile of patients who benefit most from this strategy remains unclear.
PD‐L1 Immune Checkpoint Targeted Photoactivable Liposomes (iTPALs) Prime the Stroma of Pancreatic Tumors and Promote Self‐Delivery
Authors: Chanda Bhandari, Azophi Moffat, Nimit Shah, Adil Khan, Maxwell Quaye, John Fakhry, Siddharth Soma, Austin Nguyen, Menitte Eroy, Ashritha Malkoochi, Rolf Brekken, Tayyaba Hasan, Jacopo Ferruzzi, Girgis Obaid
Journal: Advanced Healthcare Materials (2024)

Desmoplasia in pancreatic ductal adenocarcinoma (PDAC) limits the penetration and efficacy of therapies. It has been previously shown that photodynamic priming (PDP) using EGFR targeted photoactivable multi-inhibitor liposomes remediates desmoplasia in PDAC and doubles overall survival. Here, bifunctional PD-L1 immune checkpoint targeted photoactivable liposomes (iTPALs) that mediate both PDP and PD-L1 blockade are presented. iTPALs also improve phototoxicity in PDAC cells and induce immunogenic cell death. PDP using iTPALs reduces collagen density, thereby promoting self-delivery by 5.4-fold in collagen hydrogels, and by 2.4-fold in syngeneic CT1BA5 murine PDAC tumors. PDP also reduces tumor fibroblast content by 39.4%. Importantly, iTPALs also block the PD-1/PD-L1 immune checkpoint more efficiently than free α-PD-L1 antibodies. Only a single sub-curative priming dose using iTPALs provides 54.1% tumor growth inhibition and prolongs overall survival in mice by 42.9%. Overall survival directly correlates with the extent of tumor iTPAL self-delivery following PDP (Pearson's r = 0.670, p = 0.034), while no relationship is found for sham non-specific IgG constructs activated with light. When applied over multiple cycles, as is typical for immune checkpoint therapy, PDP using iTPALs promises to offer durable tumor growth delay and significant survival benefit in PDAC patients, especially when used to promote self-delivery of integrated chemo-immunotherapy regimens.
IgE in allergy: It takes two
Authors: Anouk von Borstel, Robyn E. O’Hehir, Menno C. van Zelm
Journal: Science Translational Medicine (2024)

A type 2 memory B cell subset is poised to differentiate into IgE-producing plasma cells in individuals with allergies (Ota et al . and Koenig et al .).
Intra‐Articular Injectable Biomaterials for Cartilage Repair and Regeneration
Authors: Manivannan Sivaperuman Kalairaj, Ridhi Pradhan, Waqas Saleem, Morgan M. Smith, Akhilesh K. Gaharwar
Journal: Advanced Healthcare Materials (2024)

Abstract Osteoarthritis is a degenerative joint disease characterized by cartilage deterioration and subsequent inflammatory changes in the underlying bone. Injectable hydrogels have emerged as a promising approach for controlled drug delivery in cartilage therapies. This review focuses on the latest developments in utilizing injectable hydrogels as vehicles for targeted drug delivery to promote cartilage repair and regeneration. The pathogenesis of osteoarthritis is discussed to provide a comprehensive understanding of the disease progression. Subsequently, the various types of injectable hydrogels used for intra‐articular delivery are discussed. Specifically, physically and chemically crosslinked injectable hydrogels are critically analyzed, with an emphasis on their fabrication strategies and their capacity to encapsulate and release therapeutic agents in a controlled manner. Furthermore, the potential of incorporating growth factors, anti‐inflammatory drugs, and cells within these injectable hydrogels are discussed. Overall, this review offers a comprehensive guide to navigating the landscape of hydrogel‐based therapeutics in osteoarthritis.
Ocular Gene Therapy in a Patient with Dystrophic Epidermolysis Bullosa
Authors: Arianna Tovar Vetencourt, Ibrahim Sayed-Ahmed, Jennifer Gomez, Hubert Chen, Brittani Agostini, Kate Carroll, Trevor Parry, Suma Krishnan, Alfonso L Sabater
Journal: New England Journal of Medicine (2024)

Dystrophic epidermolysis bullosa is a rare genetic disease caused by damaging variants in