tbuckley/cabot-search huggingface dataset:
Coaxial Electrospun Nanofibrous Membranes as Dual‐Functional Biomimetic Tendon Sheath for Tendon Repair and Anti‐Peritendinous Adhesion
Authors: Qiao Yang, Jianfeng Li, Hongfang Meng, Yongdi Wang, Lanlan Hu, Weiwei Su, Jie Xu, Juedong Hou, Rui Zhao, Zihan Wang, Kairui Zhang, Yaobin Wu, Ling Wang
Journal: Advanced Healthcare Materials (2024)

Abstract Tendon injuries often exhibit limited healing capacity, frequently complicated by peritendinous adhesion, posing a substantial challenge in clinical tendon repair. Although present biomaterial‐based membranes offer a promising strategy for tendon treatment, their clinical application is hindered by inflammation‐induced adhesion. Herein, this study presents a dual‐functional biomimetic tendon sheath based on a coaxial electrospun nanofibrous membrane for enhancing tendon repair and simultaneously preventing peritendinous adhesion. This nanofibrous membrane is fabricated using a coaxial electrospinning method, encapsulating celecoxib‐loaded polycaprolactone (PCL) within gelatin methacryloyl (GelMA) shell. Both in vitro and in vivo analysis results demonstrated that such coaxial biomimetic tendon sheath enhanced tenogenic differentiation of tendon stem/progenitor cells (TSPCs) due to nanofibrous GelMA shell providing a suitable microenvironment surface. Simultaneously, the sustained release of celecoxib (CEL) from the core is able to significantly decrease the expression of inflammatory cytokines. Notably, in vivo assessments in animal models with patellar tendon defects revealed significant reductions in peritendinous adhesion, leading to further enhancement in tendon repair. These results underscore the potential of the coaxial nanofibrous membrane as a dual‐functional biomimetic tendon sheath, offering a promising avenue for the long‐term management of tendon injuries.
Novel insights into the dynamic function of PRC2 in innate immunity
Authors: Rosalie W M Kempkes, Rab K Prinjha, Menno P J de Winther, Annette E Neele
Journal: Trends in Immunology (2024)

The polycomb repressive complex 2 (PRC2) is an established therapeutic target in cancer. PRC2 catalyzes methylation of histone H3 at lysine 27 (H3K27me3) and is known for maintaining eukaryote cell identity. Recent discoveries show that modulation of PRC2 not only impacts cell differentiation and tumor growth but also has immunomodulatory properties. Here, we integrate multiple immunological fields to understand PRC2 and its subunits in epigenetic canonical regulation and non-canonical mechanisms within innate immunity. We discuss how PRC2 regulates hematopoietic stem cell proliferation, myeloid cell differentiation, and shapes innate immune responses. The PRC2 catalytic domain EZH2 is upregulated in various human inflammatory diseases and its deletion or inhibition in experimental mouse models can reduce disease severity, emphasizing its importance in regulating inflammation.
Barrett’s early cancer. Should we abandon piecemeal resections?
Authors: Arjun D. Koch
Journal: Endoscopy (2024)

It is not so long ago that the debate regarding the optimal treatment of Barrett's high grade dysplasia and mucosal cancer was between surgeons advocating esophagectomy and interventional endoscopists demonstrating their results with endoscopic (piecemeal) mucosal resection (EMR) [1]. There is strong evidence to support the idea that piecemeal EMR has the same cancer-related outcomes as esophagectomy with its perfect histology specimen [1]. As such, endoscopic resection has become the first-choice treatment for high grade dysplasia and early cancer in Barrett's esophagus, including in cases with submucosal invasion down to 500 µm (sm1) in the absence of high-risk features such as lymphovascular invasion or poor tumor differentiation.
Safety and efficacy of lumen-apposing metal stents for endoscopic ultrasound-guided drainage of pancreatic fluid collections: a systematic review and meta-analysis
Authors: Vishnu Charan Suresh Kumar, Sahib Singh, Vishali Moond, Babu P. Mohan, Ganesh Aswath, Hafiz M. A. Khan, Bishnu Sapkota, Douglas G. Adler
Journal: Endoscopy (2024)

Abstract Introduction Endoscopic ultrasound (EUS)-guided drainage of pancreatic fluid collections (PFCs) has variable outcomes according to the type of lumen-apposing metal stent (LAMS) used. We aimed to perform a systematic review and meta-analysis of the available data. Methods Online databases, including EMBASE, PubMed, and SCOPUS, were searched from inception to 30 January 2024. The outcomes of interest were technical success, clinical success, adverse events (AEs), and the need for endoscopic necrosectomy. Pooled estimates stratified by the type of stent (Axios, Nagi, or Spaxus), severity of bleeding, and type of PFC were calculated using a random-effects model. Heterogeneity was assessed by I 2 values. Results 37 studies were included in the final analysis. The pooled outcomes (95%CIs) for PFC drainage using the Axios, Nagi, and Spaxus stents, respectively, were: technical success 97.7% (96.4%–98.8%), 96.9% (94.6%–98.5%), 98.2% (94.4%–99.9%); clinical success 90.9% (88.7%–92.8%), 88.5% (79.9%–95.0%), 93.5% (91.0%–95.6%); total AEs 20.4% (16.6%–24.6%), 17.1% (8.3%–28.3%), 7.6% (3.6%–13.0); migration 4.2% (2.9%–5.7%), 7.8% (4.1%–12.4%), 0.9% (0.1%–2.8%); overall bleeding 7.0% (4.9%–9.5%), 4.4% (2.2%–7.4%), 1.8% (0.8%–3.3%); and endoscopic necrosectomy 54.5% (38.9%–69.7%), 16.0% (11.4%–21.3%), 19.9% (6.6%–38.1%). In terms of severity, moderate–severe bleeding was most common with all three stents. AEs were higher in patients with walled-off necrosis compared with pseudocysts. Substantial-to-considerable heterogeneity (I 2 &gt;60%) was present for total AEs for all of the stents. Conclusion Our study shows good technical and clinical success rates with all three LAMSs for EUS-guided PFC drainage. Total AEs and bleeding were highest with the Axios stent and lowest with the Spaxus. Stent migration was highest with the Nagi stent and lowest with the Spaxus.
An active shrinkage and antioxidative hydrogel with biomimetic mechanics functions modulates inflammation and fibrosis to promote skin regeneration
Authors: Tao Zhang, Xin-Cao Zhong, Zi-Xuan Feng, Xiao-Ying Lin, Chun-Ye Chen, Xiao-Wei Wang, Kai Guo, Yi Wang, Jun Chen, Yong-Zhong Du, Ze-Ming Zhuang, Yong Wang, Wei-Qiang Tan
Journal: Bioactive Materials (2024)
To genetic rescue or not?
Authors: Karin Norén, Malin Hasselgren
Journal: Trends in Genetics (2024)

Inbreeding depression and genetic rescue are central themes in conservation biology. Translocation is a tool to assist genetic rescue but is connected to risks. A new study by Quinn et al. used genomic data to evaluate translocations as a potential action in montane red fox, bringing important implications also for other threatened species.
Imprinting of the paternal marsupial X chromosome by DNA methylation
Authors: Jennifer A M Graves
Journal: Trends in Genetics (2024)

Why is it that the X chromosome that comes from the male parent is inactivated in female marsupials, female mice, and even female mealy bugs, or the whole paternal chromosome complement in some weird flies? A new paper by Milton et al. now reveals DNA methylation patterns established in the male germline before meiosis in wallabies that may constitute the elusive paternal imprint.
Air Pollution, Genetic Susceptibility, and Risk of Incident Systemic Lupus Erythematosus: A Prospective Cohort Study: Comment on the Article by Xing et al
Authors: Na Wang, Hu Chen, Shugang Liu
Journal: Arthritis & Rheumatology (2024)

Disclosure Form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Relevance of residual tricuspid regurgitation for right ventricular reverse remodelling after tricuspid valve intervention in patients with severe tricuspid regurgitation and right‐sided heart failure
Authors: Ludwig T. Weckbach, Lukas Stolz, Philipp M. Doldi, Hannah Glaser, Cecilia Ennin, Michael Kothieringer, Thomas J. Stocker, Michael Näbauer, Mohammad Kassar, Sara Bombace, Karl‐Patrik Kresoja, Philipp Lurz, Fabien Praz, Holger Thiele, Volker Rudolph, Steffen Massberg, Jörg Hausleiter
Journal: European Journal of Heart Failure (2024)

Abstract Aims Right ventricular reverse remodelling (RVRR) is linked to improved survival in patients with severe tricuspid regurgitation (TR) and right‐sided heart failure who underwent interventional treatment. However, the role of residual TR on RVRR remains unclear. In this analysis the impact of residual TR on RVRR after interventional TR treatment, which was validated by two independent cohorts at four sites using echocardiography or cardiac magnetic resonance (CMR) imaging, was investigated. Methods and results Overall, 253 patients who were treated for severe TR and right‐sided heart failure using different treatment modalities (tricuspid transcatheter edge‐to‐edge repair [T‐TEER], transcatheter tricuspid valve annuloplasty, orthotopic transcatheter TV replacement [TTVR], heterotopic TTVR) were included. Three‐dimensional echocardiographic and CMR‐based assessment of RVRR and clinical evaluation of decongestion or exercise capacity were performed at baseline and 30 days after the procedure. Mortality was analysed at 1 year after transcatheter tricuspid valve intervention (TTVI). In patients with residual TR ≤1+ pronounced reduction of right ventricular end‐diastolic and end‐systolic volumes was observed. In patients with residual TR ≥2+ the effect of RVRR gradually decreased with higher residual TR reinforcing the relevance of optimal procedural results for RVRR. These findings were validated in two independent cohorts. In contrast to RVRR, residual TR ≤1+ and 2+ were associated with similar 1‐year survival. RVRR was only observed after T‐TEER or orthotopic TTVR, but not after heterotopic TTVR as expected. However, all three treatment modalities were accompanied by significant decongestion and functional improvement at 30‐day follow‐up. Conclusion In patients with severe TR and right‐sided heart failure undergoing TTVI, superior procedural results were associated with more pronounced RVRR.
Discontinuation and reinitiation of mineralocorticoid receptor antagonists in patients with heart failure and reduced ejection fraction
Authors: Laura Landucci, Ulrika Ljung Faxén, Lina Benson, Ulf Dahlström, Juan J. Carrero, Gianluigi Savarese, Lars H. Lund
Journal: European Journal of Heart Failure (2024)

Abstract Aims Mineralocorticoid receptor antagonists (MRA) improve outcomes in heart failure with reduced ejection fraction (HFrEF) but are underused. Point prevalent use has been described, but the kinetics of discontinuation and the extent of reinitiation have not been studied. Methods and results Patients with HFrEF enrolled in the Swedish Heart Failure Registry between 2006 and 2021 were linked to the Prescribed Drug Register. The rate of discontinuation during the first year of treatment and reinitiation the year after discontinuation were estimated using the Kaplan–Meier method. Multivariable Cox proportional hazards models were used to assess the predictors of discontinuation. Of 11 474 MRA new users, 71% remained on therapy at 1 year. Baseline characteristics independently associated with discontinuation were: estimated glomerular filtration rate (eGFR) &lt;30 ml/min/1.73 m 2 (hazard ratio [HR] 1.75, 95% confidence interval [CI] 1.34–2.27), hyperkalaemia (HR 1.73, 95% CI 1.25–2.40), eGFR 30–60 ml/min/1.73 m 2 (HR 1.51, 95% CI 1.37–1.66), age ≥80 years (HR 1.26, 95% CI 1.10–1.43), enrolment as inpatient (HR 1.25, 95% CI 1.14–1.38), a diagnosis of atrial fibrillation (HR 1.24, 95% CI 1.10–1.39), living alone (HR 1.23, 95% CI 1.13–1.34), ischaemic heart disease (HR 1.20, 95% CI 1.09–1.31), anaemia (HR 1.17, 95% CI 1.07–1.29), diabetes mellitus (HR 1.15, 95% CI 1.04–1.27) and New York Heart Association class III–IV (HR 1.13, 95% CI 1.02–1.24). Reinitiation within a year occurred in 46% of cases, mostly within 3 months after discontinuation. Conclusion Among patients with HFrEF initiated on MRA, 71% remained on therapy at 1 year. Discontinuation occurred early and was more common in patients with advanced kidney disease, hyperkalaemia, lack of follow‐up in specialty care, more severe heart failure, comorbidities, and markers of sociodemographic frailty. Among those who discontinued, almost half reinitiated treatment the year following discontinuation.
Mesenchymal precursor cells reduce mortality and major morbidity in ischaemic heart failure with inflammation: <scp>DREAM</scp>‐<scp>HF</scp>
Authors: Emerson C. Perin, Kenneth M. Borow, Timothy D. Henry, Margaret Jenkins, Olga Rutman, Jack Hayes, Christopher W. James, Eric Rose, Hicham Skali, Silviu Itescu, Barry Greenberg
Journal: European Journal of Heart Failure (2024)
Case 37-2024: A 41-Year-Old Man with Seizures and Agitation
Authors: Sheldon Benjamin, Lara Basovic, Javier M Romero, Alice D Lam, Caitlin Adams
Journal: New England Journal of Medicine (2024)

A 41-year-old man with epilepsy presented with increased seizure activity. In the hospital, the patient struck a staff member and said, "I thought they were trying to kill me." A diagnosis was made.
Effect of a Reduced PCV10 Dose Schedule on Pneumococcal Carriage in Vietnam
Authors: Lay-Myint Yoshida, Michiko Toizumi, Hien Anh Thi Nguyen, Billy J Quilty, Le Thuy Lien, Le Huy Hoang, Chihiro Iwasaki, Mizuki Takegata, Noriko Kitamura, Monica L Nation, Jason Hinds, Kevin van Zandvoort, Belinda D Ortika, Eileen M Dunne, Catherine Satzke, Hung Thai Do, Kim Mulholland, Stefan Flasche, Duc-Anh Dang
Journal: New England Journal of Medicine (2024)

BackgroundAfter pneumococcal disease and colonization have been controlled through vaccination campaigns, a reduced pneumococcal conjugate vaccine (PCV) schedule may be sufficient to sustain that control at reduced costs.MethodsWe investigated whether a single primary dose and booster dose (1p+1) of the 10-valent PCV (PCV10) would be noninferior to alternative dose schedules in sustaining control of carriage of pneumococcal serotypes included in the vaccine. In Nha Trang, Vietnam, an area in which PCV had not been used previously, a PCV10 catch-up campaign was conducted in which the vaccine was offered to children younger than 3 years of age, after which a cluster-randomized trial was conducted in which children received PCV10 at 2, 3, and 4 months of age (3p+0 group); at 2, 4, and 12 months of age (2p+1 group); at 2 and 12 months of age (1p+1 group); or at 12 months of age (0p+1 group). Annual carriage surveys in infants (4 to 11 months of age) and toddlers (14 to 24 months of age) were conducted from 2016 through 2020. The primary end point was protection against carriage of vaccine serotypes, evaluated in a noninferiority analysis in the 1p+1 group as compared with the 2p+1 and 3p+0 groups, 3.5 years after vaccine introduction (noninferiority margin, 5 percentage points). Noninferiority of the 0p+1 schedule was also evaluated.ResultsIn 2016, before the introduction of PCV10, vaccine-serotype carriage was found in 160 of 1363 infants (11.7%); in 2020, vaccine-serotype carriage was found in 6 of 333 (1.8%), 5 of 340 (1.5%), and 4 of 313 (1.3%) infants in the 1p+1, 2p+1, and 3p+0 groups, respectively, indicating noninferiority of 1p+1 to 2p+1 (difference, 0.3 percentage points; 95% confidence interval [CI], −1.6 to 2.2) and to 3p+0 (difference, 0.5 percentage points; 95% CI, −1.4 to 2.4). Similarly, 1p+1 was noninferior to 2p+1 and 3p+0 for protection against vaccine-serotype carriage among toddlers. In 2016, carriage of serotype 6A was found in 99 of 1363 infants (7.3%); in 2020, it was found in 12 of 333 (3.6%), 10 of 340 (2.9%), and 3 of 313 (1.0%) infants in the 1p+1, 2p+1, and 3p+0 groups, respectively. The 0p+1 schedule was also noninferior to the other three dose schedules among infants and toddlers, although cross-protection against serotype 6A was less common than with the other vaccination schedules. No PCV10-associated severe adverse effects were observed.ConclusionsA reduced vaccination schedule involving a single primary dose and booster dose of PCV10 was noninferior to alternative schedules in protecting against vaccine-serotype carriage in infants and toddlers. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT02961231.)
Reducing the Cost of Saving Children’s Lives
Authors: Elizabeth Miller
Journal: New England Journal of Medicine (2024)

The use of pneumococcal conjugate vaccines has been associated with a major reduction in mortality and morbidity from pneumococcal disease among young children worldwide, but these vaccines are costly. With the support of Gavi, the Vaccine Alliance, most low-income countries have introduced pneumococcal conjugate vaccines,1 but sustaining the vaccination program in countries that are no longer eligible for Gavi support is challenging, and some middle-income countries have yet to introduce pneumococcal conjugate vaccines because of cost. In this issue of the Journal, two approaches to reducing the cost of an infant pneumococcal conjugate vaccine program are described by Gallagher et . . .
Twice-Yearly Lenacapavir for HIV Prevention in Men and Gender-Diverse Persons
Authors: Colleen F Kelley, Maribel Acevedo-Quiñones, Allison L Agwu, Anchalee Avihingsanon, Paul Benson, Jill Blumenthal, Cynthia Brinson, Carlos Brites, Pedro Cahn, Valeria D Cantos, Jesse Clark, Meredith Clement, Cathy Creticos, Gordon Crofoot, Ricardo S Diaz, Susanne Doblecki-Lewis, Jorge A Gallardo-Cartagena, Aditya Gaur, Beatriz Grinsztejn, Shawn Hassler, Juan Carlos Hinojosa, Theo Hodge, Richard Kaplan, Marcus Lacerda, Anthony LaMarca, Marcelo H Losso, José Valdez Madruga, Kenneth H Mayer, Anthony Mills, Karam Mounzer, Nkosiphile Ndlovu, Richard M Novak, Alma Perez Rios, Nittaya Phanuphak, Moti Ramgopal, Peter J Ruane, Jorge Sánchez, Breno Santos, Patric Schine, Tanya Schreibman, LaShonda Y Spencer, Olivia T Van Gerwen, Ricardo Vasconcelos, Jose Gabriel Vasquez, Zwelethu Zwane, Stephanie Cox, Chris Deaton, Ramin Ebrahimi, Pamela Wong, Renu Singh, Lillian B Brown, Christoph C Carter, Moupali Das, Jared M Baeten, Onyema Ogbuagu
Journal: New England Journal of Medicine (2024)

BackgroundTwice-yearly subcutaneous lenacapavir has been shown to be efficacious for prevention of HIV infection in cisgender women. The efficacy of lenacapavir for preexposure prophylaxis (PrEP) in cisgender men, transgender women, transgender men, and gender-nonbinary persons is unclear.MethodsIn this phase 3, double-blind, randomized, active-controlled trial, we randomly assigned participants in a 2:1 ratio to receive subcutaneous lenacapavir every 26 weeks or daily oral emtricitabine–tenofovir disoproxil fumarate (F/TDF). The primary efficacy analysis compared the incidence of HIV infection in the lenacapavir group with the background HIV incidence in the screened population. The secondary efficacy analysis compared the incidence of HIV infection in the lenacapavir group with that in the F/TDF group.ResultsAmong 3265 participants who were included in the modified intention-to-treat analysis, HIV infections occurred in 2 participants in the lenacapavir group (0.10 per 100 person-years; 95% confidence interval [CI], 0.01 to 0.37) and in 9 participants in the F/TDF group (0.93 per 100 person-years; 95% CI, 0.43 to 1.77). The background HIV incidence in the screened population (4634 participants) was 2.37 per 100 person-years (95% CI, 1.65 to 3.42). The incidence of HIV infection in the lenacapavir group was significantly lower than both the background incidence (incidence rate ratio, 0.04; 95% CI, 0.01 to 0.18; P<0.001) and the incidence in the F/TDF group (incidence rate ratio, 0.11; 95% CI, 0.02 to 0.51; P=0.002). No safety concerns were identified. A total of 26 of 2183 participants (1.2%) in the lenacapavir group and 3 of 1088 (0.3%) in the F/TDF group discontinued the trial regimen because of injection-site reactions.ConclusionsThe HIV incidence with twice-yearly lenacapavir was significantly lower than the background incidence and the incidence with F/TDF. (Funded by Gilead Sciences; PURPOSE 2 ClinicalTrials.gov number, NCT04925752.)
Immunotherapy for Early-Stage Triple-Negative Breast Cancer
Authors: Harold J Burstein
Journal: New England Journal of Medicine (2024)

Early-stage triple-negative breast cancers, which lack expression of three proteins (estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2), have long been defined by what they are not. Now they have found a new identity and treatment approach: they are breast cancers that benefit from immune checkpoint inhibitor therapy. Triple-negative breast cancer is characterized by higher tumor expression of the immunomodulatory protein programmed death ligand 1 (PD-L1), greater tumor mutational burden, and more extensive tumor-infiltrating lymphocytes than other breast cancer subtypes — all of which suggested potential benefit from immunotherapy. The survival data from the KEYNOTE-522 trial that . . .
Obecabtagene Autoleucel in Adults with B-Cell Acute Lymphoblastic Leukemia
Authors: Claire Roddie, Karamjeet S. Sandhu, Eleni Tholouli, Aaron C. Logan, Paul Shaughnessy, Pere Barba, Armin Ghobadi, Manuel Guerreiro, Deborah Yallop, Mehrdad Abedi, Jeremy M. Pantin, Jean A. Yared, Amer M. Beitinjaneh, Sridhar Chaganti, Katharine Hodby, Tobias Menne, Martha L. Arellano, Ram Malladi, Bijal D. Shah, Luke Mountjoy, Kristen M. O’Dwyer, Karl S. Peggs, Pierre Lao-Sirieix, Yiyun Zhang, Wolfram Brugger, Edgar Braendle, Martin Pule, Michael R. Bishop, Daniel J. DeAngelo, Jae H. Park, Elias Jabbour
Journal: New England Journal of Medicine (2024)

Obecabtagene autoleucel (obe-cel) is an autologous 41BB-ζ anti-CD19 chimeric antigen receptor (CAR) T-cell therapy which uses an intermediate-affinity CAR to reduce toxic effects and improve persistence. We conducted a phase 1b-2 multicenter study of obe-cel in adults (≥18 years of age) with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). The main cohort, cohort 2A, included patients with morphologic disease; patients in cohort 2B had measurable residual disease. The primary end point was overall remission (complete remission or complete remission with incomplete hematologic recovery) in cohort 2A. Secondary end points included event-free survival, overall survival, and safety. Of the 153 enrolled patients, 127 (83.0%) received at least one infusion of obe-cel and were evaluable. In cohort 2A (94 patients; median follow-up, 20.3 months), overall remission occurred in 77% (95% confidence interval [CI], 67 to 85), with complete remission in 55% (95% CI, 45 to 66) and complete remission with incomplete hematologic recovery in 21% (95% CI, 14 to 31). The prespecified null hypotheses of overall remission (≤40%) and complete remission (≤20%) were rejected (P<0.001). In the 127 patients who received at least one obe-cel infusion (median follow-up, 21.5 months), the median event-free survival was 11.9 months (95% CI, 8.0 to 22.1); estimated 6- and 12-month event-free survival was 65.4% and 49.5%, respectively. The median overall survival was 15.6 months (95% CI, 12.9 to not evaluable); estimated 6- and 12-month overall survival was 80.3% and 61.1%, respectively. Grade 3 or higher cytokine release syndrome developed in 2.4% of the patients, and grade 3 or higher immune effector cell-associated neurotoxicity syndrome developed in 7.1% of the patients. Obe-cel resulted in a high incidence of durable response among adults with relapsed or refractory B-cell ALL, with a low incidence of grade 3 or higher immune-related toxic effects. (Funded by Autolus Therapeutics; FELIX ClinicalTrials.gov number, NCT04404660.).