tbuckley/cabot-search huggingface dataset:
Biomaterial Scaffolds Made of Chemically Cross‐Linked Gelatin Microsphere Aggregates (C‐GMSs) Promote Vascularized Bone Regeneration
Authors: Peiyan Wang, Xinyue Meng, Runze Wang, Wei Yang, Lanting Yang, Jianxun Wang, Dong‐An Wang, Changjiang Fan
Journal: Advanced Healthcare Materials (2022)

Various scaffolding systems have been attempted to facilitate vascularization in tissue engineering by optimizing biophysical properties (e.g., vascular-like structures, porous architectures, surface topographies) or loading biochemical factors (e.g., growth factors, hormones). However, vascularization during ossification remains an unmet challenge that hampers the repair of large bone defects. In this study, reconstructing vascularized bones in situ against critical-sized bone defects is endeavored using newly developed scaffolds made of chemically cross-linked gelatin microsphere aggregates (C-GMSs). The rationale of this design lies in the creation and optimization of cell-material interfaces to enhance focal adhesion, proliferation, and function of anchorage-dependent functional cells. In vitro trials are carried out by coculturing human aortic endothelial cells (HAECs) and murine osteoblast precursor cells (MC3T3-E1) within C-GMS scaffolds, in which endothelialized bone-like constructs are yielded. Angiogenesis and osteogenesis induced by C-GMSs scaffold are further confirmed via subcutaneous-embedding trials in nude mice. In situ trials for the repair of critical-sized femoral defects are subsequently performed in rats. The acellular C-GMSs with interconnected macropores, exhibit the capability to recruit the endogenous cells (e.g., bone-forming cells, vascular forming cells, immunocytes) and then promote vascularized bone regeneration as well as integration with host bone.
Treatment outcome of atypical EGFR mutations in the German National Network Genomic Medicine Lung Cancer (nNGM)
Authors: M. Janning, J. Süptitz, C. Albers-Leischner, P. Delpy, A. Tufman, J.-L. Velthaus-Rusik, M. Reck, A. Jung, D. Kauffmann-Guerrero, I. Bonzheim, S. Brändlein, H.-D. Hummel, M. Wiesweg, H.-U. Schildhaus, J.A. Stratmann, M. Sebastian, J. Alt, J. Buth, I. Esposito, J. Berger, L. Tögel, F.C. Saalfeld, M. Wermke, S. Merkelbach-Bruse, A.M. Hillmer, F. Klauschen, C. Bokemeyer, R. Buettner, J. Wolf, S. Loges, Ronald Simon, Guido Sauter, Alexander Volk, Jens Neumann, Frederick Klauschen, Wilko Weichert, Naser Kalhori, Reinhard Lüthen, Robert Stöhr, Chistoph Schubart, Heidemarie Wacker, Florian Fuchs, Nils Hartmann, Stefanie Graf, Christian Brandts, Peter Wild, Melanie Demes, Henning Reis, Gernot Rohde
Journal: Annals of Oncology (2022)

Atypical EGFR mutations occur in 10%-30% of non-small-cell lung cancer (NSCLC) patients with EGFR mutations and their sensitivity to classical epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI) is highly heterogeneous. Patients harboring one group of uncommon, recurrent EGFR mutations (G719X, S768I, L861Q) respond to EGFR-TKI. Exon 20 insertions are mostly insensitive to EGFR-TKI but display sensitivity to exon 20 inhibitors. Clinical outcome data of patients with very rare point and compound mutations upon systemic treatments are still sparse to date.In this retrospective, multicenter study of the national Network Genomic Medicine (nNGM) in Germany, 856 NSCLC cases with atypical EGFR mutations including co-occurring mutations were reported from 12 centers. Clinical follow-up data after treatment with different EGFR-TKIs, chemotherapy and immune checkpoint inhibitors were available from 260 patients. Response to treatment was analyzed in three major groups: (i) uncommon mutations (G719X, S7681, L861Q and combinations), (ii) exon 20 insertions and (iii) very rare EGFR mutations (very rare single point mutations, compound mutations, exon 18 deletions, exon 19 insertions).Our study comprises the largest thus far reported real-world cohort of very rare EGFR single point and compound mutations treated with different systemic treatments. We validated higher efficacy of EGFR-TKI in comparison to chemotherapy in group 1 (uncommon), while most exon 20 insertions (group 2) were not EGFR-TKI responsive. In addition, we found TKI sensitivity of very rare point mutations (group 3) and of complex EGFR mutations containing exon 19 deletions or L858R mutations independent of the combination partner. Notably, treatment responses in group 3 (very rare) were highly heterogeneous. Co-occurring TP53 mutations exerted a non-significant trend for a detrimental effect on outcome in EGFR-TKI-treated patients in groups 2 and 3 but not in group 1.Based on our findings, we propose a novel nNGM classification of atypical EGFR mutations.
Redo-endoscopic ultrasound-guided gastroenterostomy for the management of distal flange misdeployment: trust your orojejunal catheter
Authors: Giuseppe Vanella, Giuseppe Dell’Anna, Michiel Bronswijk, Maria Chiara Petrone, Schalk van der Merwe, Paolo Giorgio Arcidiacono
Journal: Endoscopy (2022)

A 60-year-old woman developed gastric outlet obstruction (GOO) due to metastatic pancreatic adenocarcinoma. Endoscopic ultrasound (EUS)-guided gastroenterostomy (EUS-GE) was planned using the Wireless Simplified Technique (WEST) [1]. Orojejunal tube (OJT) placement and jejunal instillation of saline and indigo carmine were followed by freehand placement of a 20 × 10-mm electrocautery-enhanced lumen-apposing metal stent (LAMS; Hot Axios, Boston Scientific). Despite jejunal fluid perturbation ([Fig. 1]), suggesting successful jejunal access, we observed the following: (i) no endosonographic confirmation of endojejunal placement of the distal flange after retraction; (ii) no backflow of blue dye after LAMS release; (iii) failed through-the-LAMS aspiration of contrast injected through the OJT; (iv) peritoneum visible through the stent ([Fig. 2 a–d]). Contrast injection through the OJT showed no jejunal leakage, suggesting either a type I or II misdeployment [2].
Prognostic Factors for Polyp Recurrence in Chronic Rhinosinusitis with Nasal Polyps
Authors: Junqin Bai, Julia Huang, Caroline Price, Samuel Rodeghiero, Lydia Suh, David Conley, Kevin Welch, Robert Kern, Stephanie Smith, Whitney Stevens, Atsushi Kato, Robert Schleimer, Bruce Tan
Journal: Journal of Allergy and Clinical Immunology (2022)
NANOSECOND PULSED ELECTRIC FIELD DELIVERY TO VENTRICULAR MID-MYOCARDIUM USING ACTIVE FIXATION LEADS: A PROOF-OF-CONCEPT PRECLINICAL STUDY
Authors: Nicholas Tan, Thomas Ladas, Georgios Christopoulos, Fahad Lodhi, Alan Sugrue, Jason Tri, Zhi Jiang, Kolade Agboola, Fatima Ezzeddine, Tiffany Ying Hu, Martin van Zyl, Adetola Ladejobi, Richard Connolly, Christopher DeSimone, Ammar M. Killu, Samuel J. Asirvatham, Freddy Del-Carpio Munoz
Journal: Journal of the American College of Cardiology (2022)
Curing Hepatitis C—Requires More Than a Prescription
Authors: Asha Choudhury, Mitchell H. Katz
Journal: JAMA Internal Medicine (2022)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications 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 2023 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 Internal Medicine journal
SYSTOLIC BLOOD PRESSURE ≤110 MMHG IS ASSOCIATED WITH HIGHER RISK FOR VENTRICULAR ARRHYTHMIAS IN HYPERTROPHIC CARDIOMYOPATHY
Authors: Dai-Yin Lu, Fatih Yalcin, Stefan Loy Zimmerman, Thomas H. Schindler, Theodore P. Abraham, Maria Roselle Abraham
Journal: Journal of the American College of Cardiology (2022)
Misdiagnosis rate among negative COVID-19 patients in real-life with Panbio COVID-19 antigen rapid test during 2021
Authors: Pablo Ryan, Felipe Pérez-García, Juan Torres-Macho, Carlos Bibiano, Juan Ignacio Lazo, Guillermo Castaño-Ochoa, Erick Joan Vidal-Alcántara, María José Muñoz-Gómez, Isidoro Martínez, Salvador Resino
Journal: Journal of Infection (2022)
Abstract P2-10-09: Oxysterol profiling in breast adipose tissue identifies brassicasterol and 24-hydroxycholesterol as breast cancer risk predictors
Authors: I-Chun Chen, Wen-Hung Kuo, Fu-Chang Hu, Ming-Yang Wang, Yen-Shen Lu, Dieter Lütjohann, Ching-Hung Lin
Journal: Cancer Research (2022)

Abstract Background: Hyperlipidemia and serum oxysterol levels are known to be associated with breast cancer risk. In murine model, altered oxysterol levels in adipose tissue were identified in obese mice. However, the significance of oxysterol levels in human adipose tissue and their association with breast cancer risk were largely unknown. In this study, we aimed to quantify the levels of different oxysterols in adipose tissue and to establish their association with breast cancer risk. Methods: The breast adipose tissue was collected from patients who underwent surgery at a tertiary medical center for benign breast disease or breast cancer. We have profiled oxysterol levels by liquid chromatography-mass spectrometry. Multivariate analysis was used to analyze the relationship of adipose tissue oxysterol levels and breast cancer risk. Result: Breast adipose tissue from 279 subjects (benign low risk, n=58; benign high risk, n=33, and breast cancer, n=188) collected between March 2009 and November 2014 were included in this analysis. Parity is a protective factor both for breast cancer in premenopausal and postmenopausal groups. Brassicasterol ≤0.28 ng/mg (OR=6.739, 95% C.I.=2.092-21.707, p=0.001) and age &amp;gt;40.06 years old (OR=3.774, 95% C.I.=1.328-10.722, p=0.013) in premenopausal patients; high log (7α-. hydroxycholesterol) levels (OR=6.690, 95% C.I.=1.915-23.369, p=0.003) and 24-hydroxycholesterol &amp;gt;0.92ng/mg (OR=4.539, 95% C.I.=1.153-17.866, p=0.030) in postmenopausal patients were associated with increased BC risk. Sitosterol ≤3.03ng/mg (OR=0.057, 95% C.I.= 0.016-0.205, p &amp;lt;0.0001) and brassicasterol level (OR=0.011, 95% C.I.= 0.001-0.222, p=0.003) were most important protective factors for BC in premenopausal and postmenopausal patients, respectively. Conclusion: Taken together, our study is the first cohort to prospectively profile oxysterol levels in breast adipose tissue. Brassicasterol and 24-hydroxycholesterol levels in adipose tissue predict breast cancer risk both in premenopausal and postmenopausal patients. Citation Format: I-Chun Chen, Wen-Hung Kuo, Fu-Chang Hu, Ming-Yang Wang, Yen-Shen Lu, Dieter Lütjohann, Ching-Hung Lin. Oxysterol profiling in breast adipose tissue identifies brassicasterol and 24-hydroxycholesterol as breast cancer risk predictors [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-10-09.
Differential Gain-of-Function Activity of Three p53 Hotspot Mutants <i>In Vivo</i>
Authors: Shunbin Xiong, Dhruv Chachad, Yun Zhang, Jovanka Gencel-Augusto, Mario Sirito, Vinod Pant, Peirong Yang, Chang Sun, Gilda Chau, Yuan Qi, Xiaoping Su, Elizabeth M. Whitley, Adel K. El-Naggar, Guillermina Lozano
Journal: Cancer Research (2022)

Abstract The majority of TP53 missense mutations identified in cancer patients are in the DNA-binding domain and are characterized as either structural or contact mutations. These missense mutations exhibit inhibitory effects on wild-type p53 activity. More importantly, these mutations also demonstrate gain-of-function (GOF) activities characterized by increased metastasis, poor prognosis, and drug resistance. To better understand the activities by which TP53 mutations, identified in Li–Fraumeni syndrome, contribute to tumorigenesis, we generated mice harboring a novel germline Trp53R245W allele (contact mutation) and compared them with existing models with Trp53R172H (structural mutation) and Trp53R270H (contact mutation) alleles. Thymocytes from heterozygous mice showed that all three hotspot mutations exhibited similar inhibitory effects on wild-type p53 transcription in vivo, and tumors from these mice had similar levels of loss of heterozygosity. However, the overall survival of Trp53R245W/+ and Trp53R270H/+ mice, but not Trp53R172H/+ mice, was significantly shorter than that of Trp53+/− mice, providing strong evidence for p53-mutant–specific GOF contributions to tumor development. Furthermore, Trp53R245W/+ and Trp53R270H/+ mice had more osteosarcoma metastases than Trp53R172H/+ mice, suggesting that these two contact mutants have stronger GOF in driving osteosarcoma metastasis. Transcriptomic analyses using RNA sequencing data from Trp53R172H/+, Trp53R245W/+, and Trp53R270H/+ primary osteosarcomas in comparison with Trp53+/– indicated that GOF of the three mutants was mediated by distinct pathways. Thus, both the inhibitory effect of mutant over wild-type p53 and GOF activities of mutant p53 contributed to tumorigenesis in vivo. Targeting p53 mutant–specific pathways may be important for therapeutic outcomes in osteosarcoma. Significance: p53 hotspot mutants inhibit wild-type p53 similarly but differ in their GOF activities, with stronger tumor-promoting activity in contact mutants and distinct protein partners of each mutant driving tumorigenesis and metastasis.
Structural and functional roles of non-bilayer lipid phases of chloroplast thylakoid membranes and mitochondrial inner membranes
Authors: Győző Garab, Lev S. Yaguzhinsky, Ondřej Dlouhý, Semen V. Nesterov, Vladimír Špunda, Edward S. Gasanoff
Journal: Progress in Lipid Research (2022)

The 'standard' fluid-mosaic membrane model can provide a framework for the operation of the photosynthetic and respiratory electron transport systems, the generation of the proton motive force (pmf) and its utilization for ATP synthesis according to the chemiosmotic theory. However, this model, with the bilayer organization of all lipid molecules, assigns no function to non-bilayer lipids - while in recent years it became clear that the two fundamental energy transducing membranes of the biosphere, chloroplast thylakoid membranes (TMs) and inner mitochondrial membranes (IMMs), contain large amounts of non-bilayer (non-lamellar) lipid phases. In this review, we summarize our understanding on the role of non-lamellar phases in TMs and IMMs: (i) We propose that for these membrane vesicles the dynamic exchange model (DEM) provides a more suitable framework than the 'standard' model; DEM complements the 'standard' model by assuming the co-existence of bilayer and non-bilayer phases and their interactions, which contribute to the structural dynamics of the membrane systems and safe-guard the membranes' high protein:lipid ratios. (ii) Non-bilayer phases play pivotal roles in membrane fusion and intermembrane lipid exchanges - essential processes in the self-assembly of these highly folded intricate membranes. (iii) The photoprotective, lipocalin-like lumenal enzyme, violaxanthin de-epoxidase, in its active state requires the presence of non-bilayer lipid phase. (iv) Cardiotoxins, water-soluble polypeptides, induce non-bilayer phases in mitochondria. (v) ATP synthesis, in mammalian heart IMMs, is positively correlated with the amount of non-bilayer packed lipids with restricted mobility. (vi) The hypothesized sub-compartments, due to non-lamellar phases, are proposed to enhance the utilization of pmf and might contribute to the recently documented functional independence of individual cristae within the same mitochondrion. Further research is needed to identify and characterize the structural entities associated with the observed non-bilayer phases; and albeit fundamental questions remain to be elucidated, non-lamellar lipid phases should be considered on a par with the bilayer phase, with which they co-exist in functional TMs and IMMs.
VP1-2022: Pre-specified event driven analysis of Overall Survival (OS) in the OlympiA phase III trial of adjuvant olaparib (OL) in germline BRCA1/2 mutation (gBRCAm) associated breast cancer
Authors: A.N.J. Tutt, J. Garber, R.D. Gelber, K-A. Phillips, A. Eisen, O.T. Johannsson, P. Rastogi, K.Y. Cui, S-A. Im, R. Yerushalmi, A.M. Brufsky, M. Taboada, G. Rossi, G. Yothers, C. Singer, L.E. Fein, N. Loman, D. Cameron, C. Campbell, C.E. Geyer
Journal: Annals of Oncology (2022)
PROLAPSE OF PERCUTANEOUSLY IMPLANTED INTRA-AORTIC AXILLARY BALLOON PUMP: A SINGLE CENTER EXPERIENCE OF AN UNDER-RECOGNIZED ANATOMICAL PROBLEM
Authors: Harsh Doshi, Gregary Marhefka, Indranee Rajapreyar, Mahek Shah, Jesus Eduardo Rame, Yevgeniy Brailovsky, Rene J. Alvarez, Nicholas J. Ruggiero, Michael P. Savage, David L. Fischman, Alec Vishnevsky
Journal: Journal of the American College of Cardiology (2022)
MASSIVE CORONARY THROMBOSIS IN A YOUNG PATIENT WITH COVID-19 INFECTION. A CASE REPORT.
Authors: Hiram Jonathan Zaldivar, Jorge Leal-Cavazos, Carlos Carrillo-Fernandez, Eduardo Pamplona-Avila, Victor Abraham Navarro-Lopez, Llamas-Esperón Guillermo
Journal: Journal of the American College of Cardiology (2022)
Phase 2 randomized, dose-ranging trial of CTP-543, a selective Janus Kinase inhibitor, in moderate-to-severe alopecia areata
Authors: Brett King, Natasha Mesinkovska, Paradi Mirmirani, Suzanne Bruce, Steve Kempers, Emma Guttman-Yassky, Janet L. Roberts, Amy McMichael, Maria Colavincenzo, Colleen Hamilton, Virginia Braman, James V. Cassella
Journal: Journal of the American Academy of Dermatology (2022)

BackgroundJanus kinase (JAK) activation is suggested to have a pathological role in alopecia areata (AA). CTP-543, a deuterated compound that selectively inhibits JAK1 and JAK2, is being developed as an oral treatment for AA.ObjectiveTo assess the safety and efficacy of a 24-week regimen of CTP-543 in patients with chronic, moderate-to-severe AA.MethodsIn this phase 2, randomized, double-blind, placebo-controlled, sequential-design trial, patients were randomized to receive CTP-543 (4 mg, 8 mg, or 12 mg) or placebo every 12 hours for 24 weeks.ResultsA dose-related increase was observed in the percentage of patients with ≥50% relative reduction in Severity of Alopecia Tool scores from baseline at week 24 (9% placebo, 21% 4 mg twice daily, 47% 8 mg twice daily, and 58% 12 mg twice daily), with statistical significance versus placebo (P < .001) observed for the 8-mg twice daily and 12-mg twice daily groups, with differences from placebo noted as early as 12 weeks after the initiation of treatment. Safety results were consistent with the known safety profiles of JAK inhibitors.LimitationsThese initial findings are from a relatively small controlled trial, and additional studies are needed to fully characterize the safety and efficacy of CTP-543 in adult patients with AA.ConclusionsPatients treated with CTP-543 (8 or 12 mg, twice daily) had a significant reduction in the severity of AA. Janus kinase (JAK) activation is suggested to have a pathological role in alopecia areata (AA). CTP-543, a deuterated compound that selectively inhibits JAK1 and JAK2, is being developed as an oral treatment for AA. To assess the safety and efficacy of a 24-week regimen of CTP-543 in patients with chronic, moderate-to-severe AA. In this phase 2, randomized, double-blind, placebo-controlled, sequential-design trial, patients were randomized to receive CTP-543 (4 mg, 8 mg, or 12 mg) or placebo every 12 hours for 24 weeks. A dose-related increase was observed in the percentage of patients with ≥50% relative reduction in Severity of Alopecia Tool scores from baseline at week 24 (9% placebo, 21% 4 mg twice daily, 47% 8 mg twice daily, and 58% 12 mg twice daily), with statistical significance versus placebo (P < .001) observed for the 8-mg twice daily and 12-mg twice daily groups, with differences from placebo noted as early as 12 weeks after the initiation of treatment. Safety results were consistent with the known safety profiles of JAK inhibitors. These initial findings are from a relatively small controlled trial, and additional studies are needed to fully characterize the safety and efficacy of CTP-543 in adult patients with AA. Patients treated with CTP-543 (8 or 12 mg, twice daily) had a significant reduction in the severity of AA.
Risk of Mental Health Problems in Children and Youths Following Concussion
Authors: Andrée-Anne Ledoux, Richard J. Webster, Anna E. Clarke, Deshayne B. Fell, Braden D. Knight, William Gardner, Paula Cloutier, Clare Gray, Meltem Tuna, Roger Zemek
Journal: JAMA Network Open (2022)

Concussion may exacerbate existing mental health issues. Little evidence exists on whether concussion is associated with the onset of new psychopathologies or long-term mental health problems.To investigate associations between concussion and risk of subsequent mental health issues, psychiatric hospitalizations, self-harm, or suicides.This population-based retrospective cohort study including children and youths aged 5 to 18 years with a concussion or orthopedic injury incurred between April 1, 2010, and March 31, 2020, in Ontario, Canada. Participants had no previous mental health visit in the year before the index event for cohort entry and no prior concussion or traumatic brain injury 5 years before the index visit. Data were collected from provincewide health administrative databases. Participants with concussion were included in the exposed cohort, and those with an orthopedic injury were included in the comparison cohort; these groups were matched 1:2, respectively, on age and sex.Concussion or orthopedic injury.The primary outcome was mental health problems, such as psychopathologies and psychiatric disorders, identified from health care visits in emergency departments, hospitalizations, or primary care settings. Secondary outcomes were psychiatric hospitalizations, self-harm health care visits, and death by suicide (identified in health care or vital statistics databases).A total of 152 321 children and youths with concussion (median [IQR] age, 13 [10-16] years; 86 423 [56.7%] male) and 296 482 children and youths with orthopedic injury (median [IQR] age, 13 [10-16] years; 171 563 [57.9%] male) were matched by age and sex. The incidence rates of any mental health problem were 11 141 per 100 000 person-years (exposed group) and 7960 per 100 000 person-years (unexposed group); with a difference of 3181 (95% CI, 3073-3291) per 100 000 person-years. The exposed group had an increased risk of developing a mental health issue (adjusted hazard ratio [aHR], 1.39; 95% CI, 1.37-1.40), self-harm (aHR, 1.49; 95% CI, 1.42-1.56), and psychiatric hospitalization (aHR, 1.47; 95% CI, 1.41-1.53) after a concussion. There was no statistically significant difference in death by suicide between exposed and unexposed groups (HR, 1.54; 95% CI, 0.90-2.61).Among children and youths aged 5 to 18 years, concussion was associated with an increased risk of mental health issues, psychiatric hospitalization, and self-harm compared with children and youths with an orthopedic injury.