tbuckley/cabot-search huggingface dataset:
The neglected members of the family: non-<i>BRCA</i>mutations in the Fanconi anemia/BRCA pathway and reproduction
Authors: Valeria Stella Vanni, Giovanni Campo, Raffaella Cioffi, Enrico Papaleo, Andrea Salonia, Paola Viganò, Matteo Lambertini, Massimo Candiani, Dror Meirow, Raoul Orvieto
Journal: Human Reproduction Update (2021)

BReast CAncer (BRCA) genes are extensively studied in the context of fertility and reproductive aging. BRCA proteins are part of the DNA repair Fanconi anemia (FA)/BRCA pathway, in which more than 20 proteins are implicated. According to which gene is mutated and which interactions are lost owing to the mutation, carriers and patients with monoallelic or biallelic FA/BRCA mutations exhibit very different phenotypes, from overt FA to cancer predisposition or no pathological implications. The effect of the so far neglected non-BRCA FA mutations on fertility also deserves consideration.As improved treatments allow a longer life expectancy in patients with biallelic FA mutations and overt FA, infertility is emerging as a predominant feature. We thus reviewed the mechanisms for such a manifestation, as well as whether they also occur in monoallelic carriers of FA non-BRCA mutations.Electronic databases PUBMED, EMBASE and CENTRAL were searched using the following term: 'fanconi' OR 'FANC' OR 'AND' 'fertility' OR 'pregnancy' OR 'ovarian reserve' OR 'spermatogenesis' OR 'hypogonadism'. All pertinent reports in the English-language literature were retrieved until May 2021 and the reference lists were systematically searched in order to identify any potential additional studies.Biallelic FA mutations causing overt FA disease are associated with premature ovarian insufficiency (POI) occurring in the fourth decade in women and with primary non-obstructive azoospermia (NOA) in men. Hypogonadism in FA patients seems mainly associated with a defect in primordial germ cell proliferation in fetal life. In recent small, exploratory whole-exome sequencing studies, biallelic clinically occult mutations in the FA complementation group A (Fanca) and M (Fancm) genes were found in otherwise healthy patients with isolated NOA or POI, and also monoallelic carrier status for a loss-of-function mutation in Fanca has been implicated as a possible cause for POI. In those patients with known monoallelic FA mutations undergoing pre-implantation genetic testing, poor assisted reproduction outcomes are reported. However, the mechanisms underlying the repeated failures and the high miscarriage rates observed are not fully known.The so far 'neglected' members of the FA/BRCA family will likely emerge as a relevant focus of investigation in the genetics of reproduction. Several (rather than a single) non-BRCA genes might be implicated. State-of-the-art methods, such as whole-genome/exome sequencing, and further exploratory studies are required to understand the prevalence and mechanisms for occult FA mutations in infertility and recurrent miscarriage.
Diagnosis and management of functional neurological disorder
Authors: Selma Aybek, David L Perez
Journal: BMJ (2022)

Functional neurological disorder (FND), previously regarded as a diagnosis of exclusion, is now a rule-in diagnosis with available treatments. This represents a major step toward destigmatizing the disorder, which was often doubted and deemed untreatable. FND is prevalent, generally affecting young and middle aged adults, and can cause severe disability in some individuals. An early diagnosis, with subsequent access to evidence based rehabilitative and/or psychological treatments, can promote recovery-albeit not all patients respond to currently available treatments. This review presents the latest advances in the use of validated rule-in examination signs to guide diagnosis, and the range of therapeutic approaches available to care for patients with FND. The article focuses on the two most frequently identified subtypes of FND: motor (weakness and/or movement disorders) and seizure type symptoms. Twenty two studies on motor and 27 studies on seizure type symptoms report high specificities of clinical signs (64-100%), and individual signs are reviewed. Rehabilitative interventions (physical and occupational therapy) are treatments of choice for functional motor symptoms, while psychotherapy is an emerging evidence based treatment across FND subtypes. The literature to date highlights heterogeneity in responses to treatment, underscoring that more research is needed to individualize treatments and develop novel interventions.
Efficacy and safety of enasidenib and azacitidine combination in patients with IDH2 mutated acute myeloid leukemia and not eligible for intensive chemotherapy
Authors: Sangeetha Venugopal, Koichi Takahashi, Naval Daver, Abhishek Maiti, Gautam Borthakur, Sanam Loghavi, Nicholas. J. Short, Maro Ohanian, Lucia Masarova, Ghayas Issa, Xuemei Wang, Bueso-Ramos Carlos, Musa Yilmaz, Tapan Kadia, Michael Andreeff, Farhad Ravandi, Marina Konopleva, Hagop M. Kantarjian, Courtney D. DiNardo
Journal: Blood Cancer Journal (2022)

Abstract Preclinically, enasidenib and azacitidine (ENA + AZA) synergistically enhance cell differentiation, and venetoclax (VEN), a small molecule Bcl2 inhibitor (i) is particularly effective in IDH 2 mutated acute myeloid leukemia ( IDH2 mut AML). This open label phase II trial enrolled patients (pts) with documented IDH2 mut AML. All patients received AZA 75 mg/m 2 /d x 7 d/cycle and ENA 100 mg QD continuously. Concomitant Bcl2i and FLT3i were allowed (NCT03683433).Twenty-six pts received ENA + AZA (median 68 years, range, 24–88); 7 newly diagnosed (ND) and 19 relapsed/refractory (R/R). In R/R AML patients, three had received prior ENA and none had received prior VEN. The composite complete remission rate (CRc) [complete remission (CR) or complete remission with incomplete hematologic recovery (CRi)] was 100% in ND AML, and 58% in R/R AML. Median OS was not reached in ND AML with median follow-up of 13.1 months (mo); Pts treated in first relapse had improved OS than those with ≥2 relapse (median OS not reached vs 5.2 mo; HR 0.24, 95% CI 0.07–0.79, p = 0.04). Two patients received ENA + AZA with a concomitant FLT3i, one responding ND AML patient and one nonresponding R/R AML patient. Seven R/R AML pts received ENA + AZA + VEN triplet, and with median follow up of 11.2 mo, median OS was not reached and 6-mo OS was 70%. The most frequent treatment-emergent adverse events include febrile neutropenia (23%). Adverse events of special interest included all-grade IDH differentiation syndrome (8%) and indirect hyperbilirubinemia (35%). ENA + AZA was a well-tolerated, and effective therapy for elderly pts with IDH2 mut ND AML as well as pts with R/R AML. The addition of VEN to ENA + AZA appears to improve outcomes in R/R IDH2 mut AML. Clinical trial registration information: https://clinicaltrials.gov/.NCT03683433
Reply to Bexultan Kazybay and Yingqiu Xie’s Letter to the Editor re: Herjan J.T. Coelingh Bennink, Jean-Michel Foidart, Frans M.J. Debruyne. Treatment of Serious COVID-19 with Testosterone Suppression and High-dose Estrogen Therapy. Eur Urol. In press. https://doi.org/10.1016/j.eururo.2021.06.024
Authors: Herjan J.T. Coelingh Bennink, Jean-Michel Foidart, Frans M.J. Debruyne
Journal: European Urology (2021)
Survival outcomes after radical cystectomy versus conservative management for clinical T1 high grade non-muscle invasive squamous bladder cancer: A multicenter collaboration by the European Association of Urology–Young Academic Urologists
Authors: C. Lonati, P. Baumeister, L. Afferi, A. Mari, A. Minervini, W. Krajewski, M. Borghesi, G.B. Schulz, M. Rink, F. Montorsi, F. Briganti, R. Hurle, S. Zamboni, C. Simeone, F. Soria, J.Y. Teoh, M. Roumiguié, M. Rouprêt, A. Masson-Lecomte, M.C. Mir, A. Antonelli, S.M.H. Einerhand, A. Mattei, M. Moschini
Journal: European Urology (2021)
382O Inhibition of WEE1 is effective in TP53 and RAS mutant metastatic colorectal cancer (mCRC): A randomised phase II trial (FOCUS4-C) comparing adavosertib (AZD1775) with active monitoring
Authors: J. Seligmann, D.J. Fisher, L.C. Brown, R. Adams, J. Graham, P. Quirke, S. Richman, R. Butler, E. Domingo, A. Blake, M. Braun, F. Collinson, R. Jones, E. Brown, E. De Winton, T. Humphies, R. Kaplan, R. Wilson, M. Seymour, T. Maughan
Journal: Annals of Oncology (2021)
Conditional immortalization of human atrial myocytes for the generation of in vitro models of atrial fibrillation
Authors: Niels Harlaar, Sven O. Dekker, Juan Zhang, Rebecca R. Snabel, Marieke W. Veldkamp, Arie O. Verkerk, Carla Cofiño Fabres, Verena Schwach, Lente J. S. Lerink, Mathilde R. Rivaud, Aat A. Mulder, Willem E. Corver, Marie José T. H. Goumans, Dobromir Dobrev, Robert J. M. Klautz, Martin J. Schalij, Gert Jan C. Veenstra, Robert Passier, Thomas J. van Brakel, Daniël A. Pijnappels, Antoine A. F. de Vries
Journal: Nature Biomedical Engineering (2022)
Pre-existing Castration-resistant Prostate Cancer–like Cells in Primary Prostate Cancer Promote Resistance to Hormonal Therapy
Authors: Qing Cheng, William Butler, Yinglu Zhou, Hong Zhang, Lu Tang, Kathryn Perkinson, Xufeng Chen, Xiaoyin Sara Jiang, Shannon J McCall, Brant A Inman, Jiaoti Huang
Journal: European Urology (2022)
TCT-663 Twelve months outcome in patients undergoing transfemoral aortic valve replacement (TAVR) with the repositionable and retrievable Boston Scientific Lotus valve compared with the balloon-expandable Edwards Sapien 3 device
Authors: Julia Seeger, Birgid Gonska, Christoph Rodewald, Wolfgang Rottbauer, Jochen Wöhrle
Journal: Journal of the American College of Cardiology (2016)
Blood-based biomarkers of inflammation in amyotrophic lateral sclerosis
Authors: Kim A. Staats, David R. Borchelt, Malú Gámez Tansey, James Wymer
Journal: Molecular Neurodegeneration (2022)

Abstract Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease in which many processes are detected including (neuro)inflammation. Many drugs have been tested for ALS in clinical trials but most have failed to reach their primary endpoints. The development and inclusion of different types of biomarkers in diagnosis and clinical trials can assist in determining target engagement of a drug, in distinguishing between ALS and other diseases, and in predicting disease progression rate, drug responsiveness, or an adverse event. Ideally, among other characteristics, a biomarker in ALS correlates highly with a disease process in the central nervous system or with disease progression and is conveniently obtained in a peripheral tissue. Here, we describe the state of biomarkers of inflammation in ALS by focusing on peripherally detectable and cellular responses from blood cells, and provide new (combinatorial) directions for exploration that are now feasible due to technological advancements.
Association of Longitudinal High-Sensitivity Troponin T With Mortality in Patients With Chronic Kidney Disease
Authors: Nicholas C. Chesnaye, Ehab Al-Sodany, Karolina Szummer, Peter Barany, Olof Heimbürger, Tora Almquist, Stefan Melander, Fredrik Uhlin, Friedo Dekker, Christoph Wanner, Kitty J. Jager, Marie Evans
Journal: Journal of the American College of Cardiology (2022)
Real time urethral and ureteral assessment during radical cystectomy using ex vivo optical imaging
Authors: F. Esperto, F. Prata, A. Civitella, P. Tuzzolo, L. Romei, V.G. Crimi, L. Cacciatore, C. Taffon, A. Crescenzi, R.M. Scarpa, R. Papalia
Journal: European Urology (2021)
Approximate Bayesian Computation Untangles Signatures of Contemporary and Historical Hybridization between Two Endangered Species
Authors: Hannes Dittberner, Aurelien Tellier, Juliette de Meaux
Journal: Molecular Biology and Evolution (2022)

Contemporary gene flow, when resumed after a period of isolation, can have crucial consequences for endangered species, as it can both increase the supply of adaptive alleles and erode local adaptation. Determining the history of gene flow and thus the importance of contemporary hybridization, however, is notoriously difficult. Here, we focus on two endangered plant species, Arabis nemorensis and A. sagittata, which hybridize naturally in a sympatric population located on the banks of the Rhine. Using reduced genome sequencing, we determined the phylogeography of the two taxa but report only a unique sympatric population. Molecular variation in chloroplast DNA indicated that A. sagittata is the principal receiver of gene flow. Applying classical D-statistics and its derivatives to whole-genome data of 35 accessions, we detect gene flow not only in the sympatric population but also among allopatric populations. Using an Approximate Bayesian computation approach, we identify the model that best describes the history of gene flow between these taxa. This model shows that low levels of gene flow have persisted long after speciation. Around 10 000 years ago, gene flow stopped and a period of complete isolation began. Eventually, a hotspot of contemporary hybridization was formed in the unique sympatric population. Occasional sympatry may have helped protect these lineages from extinction in spite of their extremely low diversity.
Getting to HBV cure: The promising paths forward
Authors: Scott Fung, Hannah S. J. Choi, Adam Gehring, Harry L. A. Janssen
Journal: Hepatology (2022)

Abstract Chronic HBV infection is a global public health burden estimated to impact nearly 300 million persons worldwide. Despite the advent of potent antiviral agents that effectively suppress viral replication, HBV cure remains difficult to achieve because of the persistence of covalently closed circular DNA (cccDNA), HBV‐DNA integration into the host genome, and impaired immune response. Indefinite treatment is necessary for most patients to maintain level of viral suppression. The success of direct‐acting antivirals (DAAs) for hepatitis C treatment has rejuvenated the search for a cure for chronic hepatitis B (CHB), though an HBV cure likely requires an additional layer: immunomodulators for restoration of robust immune responses. DAAs such as entry inhibitors, capsid assembly modulators, inhibitors of subviral particle release, cccDNA silencers, and RNA interference molecules have reached clinical development. Immunomodulators, namely innate immunomodulators (Toll‐like receptor agonists), therapeutic vaccines, checkpoint inhibitors, and monoclonal antibodies, are also progressing toward clinical development. The future of the HBV cure possibly lies in triple combination therapies with concerted action on replication inhibition, antigen reduction, and immune stimulation. Many obstacles remain, such as overcoming translational failures, choosing the right endpoint using the right biomarkers, and leveraging current treatments in combination regimens to enhance response rates. This review gives an overview of the current therapies for CHB, HBV biomarkers used to evaluate treatment response, and development of DAAs and immune‐targeting drugs and discusses the limitations and unanswered questions on the journey to an HBV cure.
Device center regulates 'tools of the trade'
Authors: K. Simmons
Journal: JAMA (1985)

Last March, a young man in Tucson underwent the second of three operations in a two-day marathon of ultimately unsuccessful attempts to save his life. The patient's immune system had acutely rejected a human heart transplanted just hours before, and now his surgeons needed to borrow time until another human heart could be found. They chose to implant an artificial heart. But the device wasn't the federally sanctioned Jarvik-7 artificial heart. Nor had this "Phoenix heart," named for the city in which it was developed, been tested before in humans. In fact, it had only been tested in calves for up to 12 hours. But not filing for government approval for the heart, as stipulated by the 1976 medical device amendments to the Food, Drug, and Cosmetic Act of 1938, the surgeons had apparently defied the FDA. Or had they? According to John C. Villforth, MS, director of the FDA's
150P Dysregulation of immune checkpoint proteins in newly-diagnosed early breast cancer patients
Authors: B.L. Rapoport, H. Steel, C-A. Benn, S. Nayler, T. Smit, L. Heyman, A. Theron, N. Hlatswayo, L. Kwofie, P. Meyer, R. Anderson
Journal: Annals of Oncology (2021)
Cutoff time for surgery in spermatic cord torsion: Results of a multicentric retrospective study of 2986 patients over 15 years
Authors: E. Seizilles de Mazancourt, X.M Matillon, U. Pinar, I. Duquesne, C. Plassais, V. Thi Dang, N. Ali Benali, W. Berchiche, C. Gaillard, A. Mauger De Varennes, G. Margue, F. Bardet, M. Hulin, A. Manuguerra, W. Wandoren, M. Chabenes, M. Sbizzera, V. Gaillard, F. Lannes, I. Dominique, K. Kaulanjan, L. Freton, Z-E. Khene, B. Pradère
Journal: European Urology (2021)
Teriflunomide Reduced Lesions in Pediatric Multiple Sclerosis
Authors: Anita Slomski
Journal: JAMA (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 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 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 journal
Transient Cell Cycle Induction in Cardiomyocytes to Treat Subacute Ischemic Heart Failure
Authors: Riham R.E. Abouleisa, Abou Bakr M. Salama, Qinghui Ou, Xian-Liang Tang, Mitesh Solanki, Yiru Guo, Yibing Nong, Lindsey McNally, Pawel K. Lorkiewicz, Kamal M. Kassem, Brooke M. Ahern, Krishna Choudhary, Reuben Thomas, Yu Huang, Hamzah R. Juhardeen, Aisha Siddique, Zainab Ifthikar, Sally K. Hammad, Ayman S. Elbaz, Kathryn N. Ivey, Daniel J. Conklin, Jonathan Satin, Bradford G. Hill, Deepak Srivastava, Roberto Bolli, Tamer M.A. Mohamed
Journal: Circulation (2022)

The regenerative capacity of the heart after myocardial infarction is limited. Our previous study showed that ectopic introduction of 4 cell cycle factors (4F; CDK1 [cyclin-dependent kinase 1], CDK4 [cyclin-dependent kinase 4], CCNB [cyclin B1], and CCND [cyclin D1]) promotes cardiomyocyte proliferation in 15% to 20% of infected cardiomyocytes in vitro and in vivo and improves cardiac function after myocardial infarction in mice.
CaP-based anti-inflammatory HIF-1α siRNA-encapsulating nanoparticle for rheumatoid arthritis therapy
Authors: Xuesong Liu, Ruru Guo, Shicheng Huo, Huan Chen, Qingxiang Song, Gan Jiang, Ye Yu, Jialin Huang, Shaowei Xie, Xiaoling Gao, Liangjing Lu
Journal: Journal of Controlled Release (2022)
Validity and utility of Hierarchical Taxonomy of Psychopathology (<scp>HiTOP</scp>): <scp>III</scp>. Emotional dysfunction superspectrum
Authors: David Watson, Holly F. Levin‐Aspenson, Monika A. Waszczuk, Christopher C. Conway, Tim Dalgleish, Michael N. Dretsch, Nicholas R. Eaton, Miriam K. Forbes, Kelsie T. Forbush, Kelsey A. Hobbs, Giorgia Michelini, Brady D. Nelson, Martin Sellbom, Tim Slade, Susan C. South, Matthew Sunderland, Irwin Waldman, Michael Witthöft, Aidan G.C. Wright, Roman Kotov, Robert F. Krueger
Journal: World Psychiatry (2022)

The Hierarchical Taxonomy of Psychopathology (HiTOP) is a quantitative nosological system that addresses shortcomings of traditional mental disorder diagnoses, including arbitrary boundaries between psychopathology and normality, frequent disorder co‐occurrence, substantial heterogeneity within disorders, and diagnostic unreliability over time and across clinicians. This paper reviews evidence on the validity and utility of the internalizing and somatoform spectra of HiTOP, which together provide support for an emotional dysfunction superspectrum. These spectra are composed of homogeneous symptom and maladaptive trait dimensions currently subsumed within multiple diagnostic classes, including depressive, anxiety, trauma‐related, eating, bipolar, and somatic symptom disorders, as well as sexual dysfunction and aspects of personality disorders. Dimensions falling within the emotional dysfunction superspectrum are broadly linked to individual differences in negative affect/neuroticism. Extensive evidence establishes that dimensions falling within the superspectrum share genetic diatheses, environmental risk factors, cognitive and affective difficulties, neural substrates and biomarkers, childhood temperamental antecedents, and treatment response. The structure of these validators mirrors the quantitative structure of the superspectrum, with some correlates more specific to internalizing or somatoform conditions, and others common to both, thereby underlining the hierarchical structure of the domain. Compared to traditional diagnoses, the internalizing and somatoform spectra demonstrated substantially improved utility: greater reliability, larger explanatory and predictive power, and greater clinical applicability. Validated measures are currently available to implement the HiTOP system in practice, which can make diagnostic classification more useful, both in research and in the clinic.
Comparing Addition of Radiotherapy in EGFR- and ALK-Positive NSCLC With Brain Metastases: Are We Evaluating the Optimal End Point?
Authors: Valerio Nardone, Pierpaolo Correale, Luciano Mutti, Isacco Desideri, Caterina Romeo, Pierpaolo Pastina, Pierosandro Tagliaferri, Michele Caraglia, Alfonso Reginelli, Luigi Pirtoli, Salvatore Cappabianca
Journal: Journal of Thoracic Oncology (2022)
Oncological long-term outcomes of patients under active surveillance for low-grade bladder tumors: An update from the Bladder Cancer Italian Active Surveillance (BIAS) project
Authors: R. Contieri, N. Frego, N.M. Buffi, G. Lughezzani, P. Casale, A. Saita, M. Lazzeri, P. Diana, M. Paciotti, D. Maffei, V. Fasulo, P.P. Avolio, A. Uleri, G. Guazzoni, R. Hurle
Journal: European Urology (2021)
Table of Contents
Authors: Barbara Murphy, Samira Farouk, John He, Michael Ross, Susan Ott, Hartmut Malluche, Vanda Jorgetti, Grahame Elder, Allison Fisher, Jodie Babitt, Albert Ong, Ron Gansevoort, Norbert Lameire, Adeera Levin, John Kellum, Michael Cheung, Michel Jadoul, Wolfgang Winkelmayer, Paul Stevens, Joana Martins, Dominik Haenni, Milica Bugarski, Marcello Polesel, Claus Schuh, Andrew Hall
Journal: Kidney International (2021)
Impacts of an Opioid Safety Initiative on US Veterans Undergoing Cancer Treatment
Authors: Lucas K Vitzthum, Vinit Nalawade, Paul Riviere, Mallika Marar, Timothy Furnish, Lewei A Lin, Reid Thompson, James D Murphy
Journal: JNCI Journal of the National Cancer Institute (2022)

There is limited research on how the opioid epidemic and consequent risk reduction policies have affected pain management among cancer patients. The purpose of this study was to analyze how the Opioid Safety Initiative (OSI) implemented at the Veterans Health Administration affected opioid prescribing patterns and opioid-related toxicity.
Assessment of Antibiotic Prescriptions for Lyme Disease After Modification of Reporting Language for Positive Screening Test Results
Authors: Sarah J. Willis, Noelle M. Cocoros, Myfanwy Callahan, Brian Herrick, Catherine M. Brown, Benjamin A. Kruskal, Michael Klompas
Journal: JAMA Network Open (2022)

This quality improvement study assesses whether revision of positive Lyme disease test result text was associated with decreases in the frequency of antibiotic prescriptions for patients without confirmatory results.