tbuckley/cabot-search huggingface dataset:
The GenderCOS project: study protocol for the development of two international Core Outcome Sets for genital gender affirming surgery
Authors: Philippine J. Roijer, Marleen S. Vallinga, Thomas E. Pidgeon, Aline Ceulemans, Alex Bakker, Brenda Carrière, Tina Rashid, James Bellringer, Javier Belinky, Marlon Buncamper, Shane D. Morrison, Walter P. Bouman, Mark-Bram Bouman, Margriet G. Mullender
Journal: International Journal of Transgender Health (2023)

Background: Worldwide an increasing number of transgender and gender diverse individuals are requesting genital Gender Affirming Surgery (gGAS). For both masculinizing and feminizing gGAS various procedures and techniques are employed. Current literature on gGAS reports heterogeneous, non-standardized and often ill-defined outcomes. Presently, no consensus exists on what outcomes should be evaluated in order to assess the clinical results and the effectiveness of these procedures, which precludes development of evidence-based treatment guidelines. Aims: This international consensus study aims to develop Core Outcome Sets (COS) for both masculinizing and feminizing gGAS. These represent the minimum sets of outcomes recommended to be measured and reported in all clinical trials pertaining to gGAS. Methods: Two Core Outcome Sets for masculinizing and feminizing gGAS will be developed in parallel by following the Core Outcome Measures in Effectiveness Trials (COMET) guidelines. The stages of development for each set are: i) Identify outcomes measured and reported in previous research through a systematic review of the literature; ii) Identify outcomes suggested by transgender and gender diverse individuals during focus groups and interviews; iii) Combine and structure the outcomes into a preliminary outcome list; iv) Conduct e-Delphi surveys among stakeholders (i.e. professionals in transgender healthcare and transgender individuals) in which all potential outcomes will be rated on level of importance; and v) Decide on the final COS during an online consensus meeting. Discussion: This study will produce minimum, core sets of relevant outcomes for gGAS, through reaching international consensus with key stakeholders, including transgender individuals. Development of these COS will enable the measurement and reporting of relevant and standardized outcomes, facilitating continued scientific advancement of this field.
A sociotechnical framework to assess patient-facing eHealth tools: results of a modified Delphi process
Authors: Christine Jacob, Johan Lindeque, Roman Müller, Alexander Klein, Thomas Metcalfe, Samantha L. Connolly, Florian Koerber, Roma Maguire, Fabrice Denis, Sabina C. Heuss, Marc K. Peter
Journal: npj Digital Medicine (2023)

Among the thousands of eHealth tools available, the vast majority do not get past pilot phases because they cannot prove value, and only a few have been systematically assessed. Although multiple eHealth assessment frameworks have been developed, these efforts face multiple challenges. This study aimed to address some of these challenges by validating and refining an initial list of 55 assessment criteria based on previous frameworks through a two-round modified Delphi process with in-between rounds of interviews. The expert panel (n = 57) included participants from 18 countries and 9 concerned parties. A consensus was reached on 46 criteria that were classified into foundational and contextual criteria. The 36 foundational criteria focus on evaluating the eHealth tool itself and were grouped into nine clusters: technical aspects, clinical utility and safety, usability and human centricity, functionality, content, data management, endorsement, maintenance, and developer. The 10 contextual criteria focus on evaluating the factors that vary depending on the context the tool is being evaluated for and were grouped into seven clusters: data-protection compliance, safety regulatory compliance, interoperability and data integration, cultural requirements, affordability, cost-benefit, and implementability. The classification of criteria into foundational and contextual helps us assess not only the quality of an isolated tool, but also its potential fit in a specific setting. Criteria subscales may be particularly relevant when determining the strengths and weaknesses of the tool being evaluated. This granularity enables different concerned parties to make informed decisions about which tools to consider according to their specific needs and priorities.
Pituitary stem cells: past, present and future perspectives
Authors: María Inés Pérez Millán, Leonard Y. M. Cheung, Florencia Mercogliano, Maria Andrea Camilletti, Gonzalo T. Chirino Felker, Lucia N. Moro, Santiago Miriuka, Michelle L. Brinkmeier, Sally A. Camper
Journal: Nature Reviews Endocrinology (2023)
The infant gut virome is associated with preschool asthma risk independently of bacteria
Authors: Cristina Leal Rodríguez, Shiraz A. Shah, Morten Arendt Rasmussen, Jonathan Thorsen, Ulrika Boulund, Casper-Emil Tingskov Pedersen, Josué L. Castro-Mejía, Christina Egeø Poulsen, Casper Sahl Poulsen, Ling Deng, Frej Andreas Nøhr Larsen, Michael Widdowson, Yichang Zhang, Søren J. Sørensen, Sylvain Moineau, Marie-Agnès Petit, Bo Chawes, Klaus Bønnelykke, Dennis S. Nielsen, Jakob Stokholm
Journal: Nature Medicine (2023)
Skin manifestations after immunisation with an adjuvanted recombinant zoster vaccine, Germany, 2020
Authors: Stefano Orru', Sibylle Bierbaum, Alexander Enk, Hartmut Hengel, Marcus Hoffelner, Daniela Huzly, Brigitte Keller-Stanislawski, Vera Mahler, Maja Mockenhaupt, Doris Oberle
Journal: Eurosurveillance (2023)

Background Shortly after the launch of a novel adjuvanted recombinant zoster vaccine (RZV), Shingrix, cases of suspected herpes zoster (HZ) or zoster-like skin reactions following immunisation were reported. Aim We aimed to investigate if these skin manifestations after administration of RZV could be HZ. Methods Between April and October 2020, general practitioners (GP) reporting a suspected case of HZ or zoster-like skin manifestation after RZV vaccination to the Paul-Ehrlich-Institut, the German national competent authority, were invited to participate in the study. The GP took a sample of the skin manifestation, photographed it and collected patient information on RZV vaccination and the suspected adverse event. We analysed all samples by PCR for varicella-zoster virus (VZV) and herpes-simplex virus (HSV) and genotyped VZV-positive samples. In addition, cases were independently assessed by two dermatologists. Results Eighty eligible cases were enrolled and 72 could be included in the analysis. Of the 72 cases, 45 were female, 33 were 60–69 years old, 32 had skin symptoms in the thoracic and 27 in the cervical dermatomes. Twenty-seven samples tested PCR positive for VZV (all genotyped as wild-type, WT), three for HSV-1 and five for HSV-2. Conclusion It may be difficult to distinguish HZ, without a PCR result, from other zoster-like manifestations. In this study, VZV-PCR positive dermatomal eruptions occurring in the first weeks after immunisation with RZV were due to WT VZV, which is not unexpected as HZ is a common disease against which the vaccine is unlikely to provide full protection at this time.
Prospective 25-year surveillance of prion diseases in France, 1992 to 2016: a slow waning of epidemics and an increase in observed sporadic forms
Authors: Angéline Denouel, Jean-Philippe Brandel, Laurène Peckeu-Abboud, Danielle Seilhean, Elodie Bouaziz-Amar, Isabelle Quadrio, Jean-Baptiste Oudart, Sylvain Lehmann, Pantxika Bellecave, Jean-Louis Laplanche, Stéphane Haik
Journal: Eurosurveillance (2023)

Background Prion diseases are rare, fatal disorders that have repeatedly raised public health concerns since the early 1990s. An active prion disease surveillance network providing national level data was implemented in France in 1992. Aim We aimed to describe the epidemiology of sporadic, genetic and infectious forms of prion diseases in France since surveillance implementation. Methods We included all suspected cases notified from January 1992 to December 2016, and cases who died during the period with a definite or probable prion disease diagnosis according to EuroCJD criteria. Demographic, clinical, genetic, neuropathological and biochemical data were collected. Results In total, 25,676 suspected cases were notified and 2,907 were diagnosed as prion diseases, including 2,510 (86%) with sporadic Creutzfeldt–Jakob disease (sCJD), 240 (8%) genetic and 157 (6%) with infectious prion disease. Suspected cases and sCJD cases increased over time. Younger sCJD patients (≤ 50 years) showed phenotypes related to a distinct molecular subtype distribution vs those above 50 years. Compared to other European countries, France has had a higher number of cases with iatrogenic CJD after growth hormone treatment and variant CJD (vCJD) linked to bovine spongiform encephalopathy (second after the United Kingdom), but numbers slowly decreased over time. Conclusion We observed a decrease of CJD infectious forms, demonstrating the effectiveness of measures to limit human exposure to exogenous prions. However, active surveillance is needed regarding uncertainties about future occurrences of vCJD, possible zoonotic potential of chronic wasting diseases in cervids and increasing trends of sCJD observed in France and other countries.
Beyond the exome: utility of long-read whole genome sequencing in exome-negative autosomal recessive diseases
Authors: Lama AlAbdi, Hanan E. Shamseldin, Ebtissal Khouj, Rana Helaby, Bayan Aljamal, Mashael Alqahtani, Aisha Almulhim, Halima Hamid, Mais O. Hashem, Firdous Abdulwahab, Omar Abouyousef, Amal Jaafar, Tarfa Alshidi, Mohammed Al-Owain, Amal Alhashem, Saeed Al Tala, Arif O. Khan, Elham Mardawi, Hisham Alkuraya, Eissa Faqeih, Manal Afqi, Salwa Alkhalifi, Zuhair Rahbeeni, Samya T. Hagos, Wijdan Al-Ahmadi, Seba Nadeef, Sateesh Maddirevula, Khalid S. A. Khabar, Alexander Putra, Angel Angelov, Changsook Park, Ana M. Reyes-Ramos, Husen Umer, Ikram Ullah, Patrick Driguez, Yoshinori Fukasawa, Ming Sin Cheung, Imed Eddine Gallouzi, Fowzan S. Alkuraya
Journal: Genome Medicine (2023)

Abstract Background Long-read whole genome sequencing (lrWGS) has the potential to address the technical limitations of exome sequencing in ways not possible by short-read WGS. However, its utility in autosomal recessive Mendelian diseases is largely unknown. Methods In a cohort of 34 families in which the suspected autosomal recessive diseases remained undiagnosed by exome sequencing, lrWGS was performed on the Pacific Bioscience Sequel IIe platform. Results Likely causal variants were identified in 13 (38%) of the cohort. These include (1) a homozygous splicing SV in TYMS as a novel candidate gene for lethal neonatal lactic acidosis, (2) a homozygous non-coding SV that we propose impacts STK25 expression and causes a novel neurodevelopmental disorder, (3) a compound heterozygous SV in RP1L1 with complex inheritance pattern in a family with inherited retinal disease, (4) homozygous deep intronic variants in LEMD2 and SNAP91 as novel candidate genes for neurodevelopmental disorders in two families, and (5) a promoter SNV in SLC4A4 causing non-syndromic band keratopathy. Surprisingly, we also encountered causal variants that could have been identified by short-read exome sequencing in 7 families. The latter highlight scenarios that are especially challenging at the interpretation level. Conclusions Our data highlight the continued need to address the interpretation challenges in parallel with efforts to improve the sequencing technology itself. We propose a path forward for the implementation of lrWGS sequencing in the setting of autosomal recessive diseases in a way that maximizes its utility.
LILRB3 Modulates Acute Myeloid Leukemia Progression and Acts as an Effective Target for CAR T-cell Therapy
Authors: Sunny Mai, Alan Hodges, Hui-Ming Chen, Jilu Zhang, Yi-Ling Wang, Yongbin Liu, Fumiko Nakatsu, Xiaoxuan Wang, Jing Fang, Yitian Xu, Vitaliy Davidov, Kyeongah Kang, Sai Ravi Pingali, Siddhartha Ganguly, Masataka Suzuki, Marina Konopleva, Brooke Prinzing, Youli Zu, Stephen Gottschalk, Yong Lu, Shu-Hsia Chen, Ping-Ying Pan
Journal: Cancer Research (2023)

Abstract Identifying novel cell surface receptors that regulate leukemia cell differentiation and can be targeted to inhibit cellular proliferation is crucial to improve current treatment modalities in acute myeloid leukemia (AML), especially for relapsed or chemotherapy-refractory leukemia. Leukocyte immunoglobulin-like receptor type B (LILRB) is an immunomodulatory receptor originally found to be expressed in myeloid cells. In this study, we found that LILRB receptors can be induced under inflammatory stimuli and chemotherapy treatment conditions. Blockade of LILRB3 inhibited leukemia cell proliferation and leukemia progression. In addition, treatment with LILRB3 blocking antibodies upregulated myeloid lineage differentiation transcription factors, including PU.1, C/EBP family, and IRF, whereas phosphorylation of proliferation regulators, for example, AKT, cyclin D1, and retinoblastoma protein, was decreased. Conversely, transcriptomic analysis showed LILRB3 activation by agonist antibodies may enhance leukemia survival through upregulation of cholesterol metabolism, which has been shown to promote leukemia cell survival. Moreover, LILRB3-targeted CAR T cells exhibited potent antitumor effects both in vitro and in vivo. Taken together, our results suggest that LILRB3 is a potentially potent target for multiple treatment modalities in AML. Significance: LILRB3 regulates differentiation and proliferation in acute myeloid leukemia and can be targeted with monoclonal antibodies and CAR T cells to suppress leukemia growth.
Citron Kinase Is a Druggable Target in Treatment-Resistant Prostate Cancer
Authors: Rashmi Mishra, Steven Blinka, Andrew C. Hsieh
Journal: Cancer Research (2023)

Abstract Prolonged treatment with androgen deprivation therapy (ADT) inevitably leads to castration-resistant prostate cancer (CRPC). Development of novel androgen-targeting agents and chemo/radiotherapies has resulted in improved survival. However, metastatic CRPC remains incurable. New therapeutics are greatly needed, and exploration of novel pathways such as the mechanisms underlying prostate cancer cell proliferation could potentially augment the natural course of CRPC. In the latest issue of Cancer Research, Rawat and colleagues delved deeply into the mechanistic role of citron kinase (CIT) in orchestrating prostate cancer proliferation and revealed its catalytic activity as a druggable target for treatment-resistant prostate cancer. The researchers utilized in vitro and in vivo methodologies to elucidate the function of CIT in mediating uncontrolled interphase progression and prostate cancer growth. Furthermore, the authors employed both androgen receptor–dependent and independent models to validate the significance of CIT kinase activity as a crucial factor in driving treatment-resistant prostate cancer growth. At a mechanistic level they determined that the E2F2-Skp2-p27 axis regulates CIT expression. Finally, they defined the landscape of CIT substrates in prostate cancer that encompasses a spectrum of cellular functions that spans key proliferation regulators to alternative splicing events. This comprehensive work provides insights into CIT as a potential biomarker for prostate cancer treatment resistance and disease progression and establishes the CIT kinase domain as a druggable target in CRPC. See related article by Rawat et al., p. 4142
Battle of the biopsies: Role of tissue and liquid biopsy in hepatocellular carcinoma
Authors: Brandon M. Lehrich, Josephine Zhang, Satdarshan P. Monga, Renumathy Dhanasekaran
Journal: Journal of Hepatology (2023)

The diagnosis and management of hepatocellular carcinoma (HCC) have improved significantly in recent years. With the introduction of immunotherapy-based combination therapy, there has been a notable expansion in treatment options for patients with unresectable HCC. Simultaneously, innovative molecular tests for early detection and management of HCC are emerging. This progress prompts a key question: as liquid biopsy techniques rise in prominence, will they replace traditional tissue biopsies, or will both techniques remain relevant? Given the ongoing challenges of early HCC detection, including issues with ultrasound sensitivity, accessibility, and patient adherence to surveillance, the evolution of diagnostic techniques is more relevant than ever. Furthermore, the accurate stratification of HCC is limited by the absence of reliable biomarkers which can predict response to therapies. While the advantages of molecular diagnostics are evident, their potential has not yet been fully harnessed, largely because tissue biopsies are not routinely performed for HCC. Liquid biopsies, analysing components such as circulating tumour cells, DNA, and extracellular vesicles, provide a promising alternative, though they are still associated with challenges related to sensitivity, cost, and accessibility. The early results from multi-analyte liquid biopsy panels are promising and suggest they could play a transformative role in HCC detection and management; however, comprehensive clinical validation is still ongoing. In this review, we explore the challenges and potential of both tissue and liquid biopsy, highlighting that these diagnostic methods, while distinct in their approaches, are set to jointly reshape the future of HCC management.
Mitochondrial ribosomal protein L12 potentiates hepatocellular carcinoma by regulating mitochondrial biogenesis and metabolic reprogramming
Authors: Xingzhao Ji, Zhen Yang, Chensheng Li, Suwei Zhu, Yu Zhang, Fuyuan Xue, Shengnan Sun, Tingting Fu, Can Ding, Yi Liu, Qiang Wan
Journal: Metabolism (2023)
The impact of thrombosis on probabilities of death and disease progression in polycythemia vera: a multistate transition analysis of 1,545 patients
Authors: Tiziano Barbui, Alessandra Carobbio, Juergen Thiele, Naseema Gangat, Elisa Rumi, Alessandro Rambaldi, Alessandro M. Vannucchi, Ayalew Tefferi, Georg Jeryczynski, Leonhard Müllauer, Rakhee Vaidya, Nanna H. Sulai, Animesh Pardanani, Dirk R. Larson, Mario Cazzola, Ilaria Casetti, Guido Finazzi, Lisa Pieri, Heinz Gisslinger, Bettina Gisslinger, Francesco Rodeghiero, Marco Ruggeri, Maria Luigia Randi, Irene Bertozzi, Francesco Passamonti
Journal: Blood Cancer Journal (2023)

We applied a parametric Markov five-state model, on a well-characterized international cohort of 1,545 patients with polycythemia vera (PV; median age 61 years; females 51%), in order to examine the impact of incident thrombosis on the trajectory of death or disease progression. At a median follow-up of 6.9 years, 347 (23%) deaths, 50 (3%) blast phase (BP), and 138 (9%) fibrotic (post-PV MF) transformations were recorded. Incident thrombosis occurred at a rate of 2.62% pt/yr (arterial 1.59% and venous 1.05%). The probability of death, in the first 10 years, for 280 (18%) patients who developed thrombosis during follow-up was 40%, which was two-fold higher than that seen in the absence of thrombosis or any other transition state (20%; p < 0.01); the adverse impact from thrombosis was more apparent for arterial (HR 1.74; p < 0.01) vs venous thrombosis (p=NS) and was independent of other fixed (i.e., age, prior venous thrombosis, leukocytosis) or time-dependent (i.e., progression to BP or MF) risk variables. The transition probability to post-PV MF increased over time, in a linear fashion, with a rate of 5% capped at 5 and 10 years, in patients with or without incident thrombosis, respectively. The impact of thrombosis on transition probability to death or post-PV MF tapered off beyond 10 years and appeared to reverse direction of impact on MF evolution at the 12-year time point. These observations suggest thrombosis in PV to be a marker of aggressive disease biology or a disease-associated inflammatory state that is consequential to both thrombosis and disease progression.
Retraction: Loss of Metallothionein Predisposes Mice to Diethylnitrosamine-Induced Hepatocarcinogenesis by Activating NF-κB Target Genes
Authors: Sarmila Majumder, Satavisha Roy, Thomas Kaffenberger, Bo Wang, Stefan Costinean, Wendy Frankel, Anna Bratasz, Periannan Kuppusamy, Tsonwin Hai, Kalpana Ghoshal, Samson T. Jacob
Journal: Cancer Research (2023)

This article (1) has been retracted at the request of the editors. Following an internal review, it was determined that:In Fig. 4A, there appears to be splicing between the final two lanes (WT/CON − WT oligo and WT/Con + WT oligo).In Fig. 5A, 11 GAPDH bands are shown while only 10 PAI-1 bands are shown.The same image was used to represent GAPDH Western blot bands in Fig. 5E and the upper Total MAPK Western blot bands in Fig. 6C.In Supplementary Fig. S4, the same image was used to represent the Ku-70 Western blot band in lane 10 and lane 14.A copy of this Retraction Notice was sent to the last known email addresses for 11 of the 11 authors. One author (Wendy Frankel) agreed to the retraction; 2 authors (Sarmila Majumder, Samson T. Jacob) did not agree to the retraction; 8 authors (Satavisha Roy, Thomas Kaffenberger, Bo Wang, Stefan Costinean, Anna Bratasz, Periannan Kuppusamy, Tsonwin Hai, Kalpana Ghoshal) did not respond. Samson T. Jacob did not agree to the retraction and stands by the reproducibility of the experimental data and the conclusions of the paper.
Retraction: Methylation Mediated Silencing of MicroRNA-1 Gene and Its Role in Hepatocellular Carcinogenesis
Authors: Jharna Datta, Huban Kutay, Mohd W. Nasser, Gerard J. Nuovo, Bo Wang, Sarmila Majumder, Chang-Gong Liu, Stefano Volinia, Carlo M. Croce, Thomas D. Schmittgen, Kalpana Ghoshal, Samson T. Jacob
Journal: Cancer Research (2023)

In Fig. 5A, the Western blot bands showing FOXP1 and GAPDH expression in SK-Hep1 cells were also used to show FOXP1 and GAPDH expression in SNU-449 cells.
Retraction: Physical and Functional Interaction of DNA Methyltransferase 3A with Mbd3 and Brg1 in Mouse Lymphosarcoma Cells
Authors: Jhrana Datta, Sarmila Majumder, Shoumei Bai, Kalpana Ghoshal, Huban Kutay, David Spencer Smith, John W. Crabb, Samson T. Jacob
Journal: Cancer Research (2023)

This article (1) has been retracted at the request of the editors. Following an institutional review by The Ohio State University (Columbus, OH), the primary affiliation for several of the authors, it was determined that in Fig. 1C, the same bands were used to show HDAC1 expression in lanes 2 to 4 as well as in lanes 7 to 9. In addition, the editors determined that the bands shown in Fig. 3C appear to have been altered by stretching or resizing and reused within the figure. As a result of these findings, the institution recommended retraction and, upon internal review, the editors agreed with this recommendation.A copy of this Retraction Notice was sent to the last known e-mail addresses for 7 of the 8 authors. Two authors (Sarmila Majumder and Samson T. Jacob) did not agree to the retraction; 5 authors (Jhrana Datta, Shoumei Bai, Kalpana Ghoshal, Huban Kutay, and John W. Crabb) did not respond; the 1 remaining author (David Spencer Smith) could not be located. Samson T. Jacob did not agree to the retraction and stands by the reproducibility of the experimental data and the conclusions of the article.