tbuckley/cabot-search huggingface dataset:
The detection of a PI-RADS 4-5 lesion at multiparametric MRI before confirmatory biopsy. Is the strongest predictor of disease progression among men with low-risk prostate cancer included in an active surveillance prospective protocol
Authors: L. Nocera, G. Gandaglia, R. Leni, E. Mazzone, C. Bravi, A. Martini, G. Rosiello, S. Scuderi, F. Barletta, D. Cannoletta, G. Cirulli, M. De Angelis, L. Sciacqua, E. Camisassa, A. Stabile, N. Fossati, F. Montorsi, A. Briganti
Journal: European Urology (2021)
P-190 A retrospective study of regorafenib versus trifluridine/tipiracil efficacy in chemorefractory metastatic colorectal cancer patients: Multi-institution real-life clinical data
Authors: P. Vitale, N. Zanaletti, P. Lombardi, M. Milanesio, V. De Falco, M. Terminiello, E. Giunta, P. Vitiello, V. Caputo, C. Borrelli, G. Arrichiello, L. Poliero, D. Ciardiello, S. Napolitano, G. Martini, E. Martinelli, V. Famiglietti, E. Fenocchio, S. Roselló Keränen, A. Cervantes, F. Ciardiello, T. Troiani
Journal: Annals of Oncology (2020)
Luminal primary muscle-invasive bladder cancer patients are less likely to benefit from platinum-based neoadjuvant chemotherapy
Authors: J.L. Boormans, J.J. De Jong, V.Y.T. Liu, T.A. Bismar, S.A. Boorjian, H-C. Huang, E. Davicioni, O.Y. Mian, J.L. Wright, A. Necchi, M. Dall’Era, H.Z. Kaimakliotis, P.C. Black, E.A. Gibb, Y. Lotan
Journal: European Urology (2021)
Performance of Noninvasive Tests of Fibrosis Among Asians, Hispanic, and non-Hispanic Whites in the STELLAR Trials
Authors: Vincent Wai-Sun Wong, Won Young Tak, George Boon Bee Goh, Pin-Nan Cheng, Eric J. Lawitz, Zobair M. Younossi, Raj Vuppalanchi, Ziad Younes, Naim Alkhouri, Lulu Wang, Jialuo Liu, Kathryn Kersey, Robert P. Myers, Stephen A. Harrison, Zachary Goodman, Michael Trauner, Manuel Romero-Gomez, Quentin M. Anstee, Mindie H. Nguyen, Takeshi Okanoue
Journal: Clinical Gastroenterology and Hepatology (2022)

The effect of race on routinely available noninvasive tests of fibrosis is incompletely understood. This study evaluated the performance of noninvasive tests among white and Asian patients in the STELLAR trials (NCT03053050 and NCT03053063), which evaluated selonsertib in patients with advanced (F3-F4) fibrosis due to nonalcoholic steatohepatitis (NASH).Baseline liver biopsies were centrally read using the NASH Clinical Research Network system, and 4 noninvasive tests (Nonalcoholic fatty liver disease fibrosis score [NFS], Fibrosis-4 index [FIB-4], Enhanced Liver Fibrosis test [ELF], and liver stiffness by vibration-controlled transient elastography) were measured. The performance of these tests to discriminate advanced fibrosis was evaluated using areas under the receiver operating characteristics curves with 5-fold cross-validation repeated 100 times.Among 3207 patients screened with evaluable liver histology, 2281 were whites and 762 were Asians. Seventy-two percent of whites and 67% of Asians had advanced fibrosis. The areas under the receiver operating characteristics curves of the noninvasive tests for advanced fibrosis were similar in whites and Asians: 0.73 and 0.75 for NFS, 0.78 and 0.80 for FIB-4, 0.79 and 0.81 for ELF, and 0.80 and 0.83 for liver stiffness, respectively. At the published cutoffs, the tests had similar sensitivities and specificities in the 2 groups. However, the sensitivities of NFS, FIB-4, and ELF were low in both white and Asian patients younger than 40 years.In the global phase III STELLAR trials, the diagnostic performance of routinely available noninvasive tests for the detection of advanced fibrosis due to NASH was acceptable and similar between white and Asian patients.
Impact of socioeconomic position on initiation of SGLT-2 inhibitors or GLP-1 receptor agonists in patients with type 2 diabetes – a Danish nationwide observational study
Authors: Alexander C. Falkentoft, Julie Andersen, Mariam Elmegaard Malik, Christian Selmer, Peter Haulund Gæde, Peter Bisgaard Staehr, Mark A. Hlatky, Emil Fosbøl, Lars Køber, Christian Torp-Pedersen, Gunnar H. Gislason, Thomas Alexander Gerds, Morten Schou, Niels E. Bruun, Anne-Christine Ruwald
Journal: The Lancet Regional Health - Europe (2022)

Low socioeconomic position may affect initiation of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucacon-like-peptide-1 receptor agonists (GLP-1RA) among patients with type 2 diabetes (T2D). We examined the association between socioeconomic position and initiation of SGLT-2i or GLP-1RA in patients with T2D at time of first intensification of antidiabetic treatment.Through nationwide registers, we identified all Danish patients on metformin who initiated second-line add-on therapy between December 10, 2012, and December 31, 2020. For each time period (2012-2014, 2015-2017, and 2018-2020), we used multivariable multinomial logistic regression to associate disposable income, as proxy for socioeconomic position, with the probability of initiating a specific second-line treatment at time of first intensification. We reported probabilities standardised to the distribution of demographics and comorbidities of patients included in the last period (2018-2020).We included 48915 patients (median age 62 years; 61·7% men). In each time period, high-income patients were more often men and had less comorbidities as compared with low income-patients. In each time period, the standardised probability of initiating a SGLT-2i or a GLP-1RA was significantly higher in the highest income group compared with the lowest: 11·4% vs. 9·5% (probability ratio [PR] 1·21, 95 % confidence interval [CI] 1·01-1·44) in 2012-2014; 22·6% vs. 19.6% (PR 1·15, CI 1·05-1·27) in 2015-2017; and 65·8% vs. 54·8% (PR 1·20, CI 1·16-1·24) in 2018-2020. The differences by income were consistent across multiple subgroups.Despite a universal healthcare system, low socioeconomic position was consistently associated with a lower probability of initiating a SGLT-2i or a GLP-1RA. These disparities may widen the future socioeconomic gap in cardiovascular outcomes.The work was funded by unrestricted grants from 'Region Sjaelland Den Sundhedsvidenskabelige Forskningsfond' and 'Murermester Lauritz Peter Christensen og hustru Kirsten Sigrid Christensens Fond'.
The Role of DNA Methylation in Genome Defense in Cnidaria and Other Invertebrates
Authors: Hua Ying, David C Hayward, Alexander Klimovich, Thomas C G Bosch, Laura Baldassarre, Teresa Neeman, Sylvain Forêt, Gavin Huttley, Adam M Reitzel, Sebastian Fraune, Eldon E Ball, David J Miller
Journal: Molecular Biology and Evolution (2022)

Considerable attention has recently been focused on the potential involvement of DNA methylation in regulating gene expression in cnidarians. Much of this work has been centered on corals, in the context of changes in methylation perhaps facilitating adaptation to higher seawater temperatures and other stressful conditions. Although first proposed more than 30 years ago, the possibility that DNA methylation systems function in protecting animal genomes against the harmful effects of transposon activity has largely been ignored since that time. Here, we show that transposons are specifically targeted by the DNA methylation system in cnidarians, and that the youngest transposons (i.e., those most likely to be active) are most highly methylated. Transposons in longer and highly active genes were preferentially methylated and, as transposons aged, methylation levels declined, reducing the potentially harmful side effects of CpG methylation. In Cnidaria and a range of other invertebrates, correlation between the overall extent of methylation and transposon content was strongly supported. Present transposon burden is the dominant factor in determining overall level of genomic methylation in a range of animals that diverged in or before the early Cambrian, suggesting that genome defense represents the ancestral role of CpG methylation.
Long-term safety and efficacy of lentiviral hematopoietic stem/progenitor cell gene therapy for Wiskott–Aldrich syndrome
Authors: A. Magnani, M. Semeraro, F. Adam, C. Booth, L. Dupré, E. C. Morris, A. Gabrion, C. Roudaut, D. Borgel, A. Toubert, E. Clave, C. Abdo, G. Gorochov, R. Petermann, M. Guiot, M. Miyara, D. Moshous, E. Magrin, A. Denis, F. Suarez, C. Lagresle, A. M. Roche, J. Everett, A. Trinquand, M. Guisset, J. Xu Bayford, S. Hacein-Bey-Abina, A. Kauskot, R. Elfeky, C. Rivat, S. Abbas, H. B. Gaspar, E. Macintyre, C. Picard, F. D. Bushman, A. Galy, A. Fischer, E. Six, A. J. Thrasher, M. Cavazzana
Journal: Nature Medicine (2022)

Abstract Patients with Wiskott–Aldrich syndrome (WAS) lacking a human leukocyte antigen-matched donor may benefit from gene therapy through the provision of gene-corrected, autologous hematopoietic stem/progenitor cells. Here, we present comprehensive, long-term follow-up results (median follow-up, 7.6 years) (phase I/II trial no. NCT02333760 ) for eight patients with WAS having undergone phase I/II lentiviral vector-based gene therapy trials (nos. NCT01347346 and NCT01347242 ), with a focus on thrombocytopenia and autoimmunity. Primary outcomes of the long-term study were to establish clinical and biological safety, efficacy and tolerability by evaluating the incidence and type of serious adverse events and clinical status and biological parameters including lentiviral genomic integration sites in different cell subpopulations from 3 years to 15 years after gene therapy. Secondary outcomes included monitoring the need for additional treatment and T cell repertoire diversity. An interim analysis shows that the study meets the primary outcome criteria tested given that the gene-corrected cells engrafted stably, and no serious treatment-associated adverse events occurred. Overall, severe infections and eczema resolved. Autoimmune disorders and bleeding episodes were significantly less frequent, despite only partial correction of the platelet compartment. The results suggest that lentiviral gene therapy provides sustained clinical benefits for patients with WAS.
Bortezomib Versus Non-Bortezomib Based Treatment for Transplant Ineligible Patients with Light Chain Amyloidosis
Authors: Surbhi Sidana, Nidhi Tandon, Angela Dispenzieri, Morie A. Gertz, Francis Buadi, Martha Q. Lacy, David Dingli, Amie Fonder, Suzanne R. Hayman, Miriam Hobbs, Wilson I Gonsalves, Yi L. Hwa, Prashant Kapoor, Robert A. Kyle, Nelson Leung, Ronald S. Go, John A Lust, Stephen J. Russell, Steven R. Zeldenrust, S. Vincent Rajkumar, Shaji Kumar
Journal: Blood (2016)
Positron Emission Tomography (PET) Guided Therapy of Aggressive Lymphomas - Interim PET-Based Outcome Prediction and Treatment Changes in Patients with B Cell Lymphomas Participating in the PETAL Trial
Authors: Ulrich Duehrsen, Stefan P Müller, Jan Rekowski, Bernd Hertenstein, Christiane Franzius, Rolf Mesters, Matthias Weckesser, Frank Kroschinsky, Jörg Kotzerke, Anke Franzke, Frank M Bengel, Paul La Rosée, Martin Freesmeyer, Heinz-Gert Hoeffkes, Andreas Hertel, Dirk Behringer, Gabriele Prange-Krex, Martin Griesshammer, Jens Holzinger, Stefan Wilop, Thomas Krohn, Aruna Raghavachar, Georg Maschmeyer, Ingo Brink, Roland Schroers, Tobias Gaska, Tu-Anh Dang, Aristoteles Giagounidis, Ariane Dienst, Hubertus Hautzel, Ralph Naumann, Alfred Klein, Dennis Hahn, Gabriele Pöpperl, Matthias Grube, Jörg Marienhagen, Andreas Schwarzer, Lars Kurch, Thomas Höhler, Heike Steiniger, Holger Nückel, Thomas Südhoff, Wolfgang Römer, Marcus Brinkmann, Claudia Ose, Dieter Hoelzer, Jan Dürig, Karl-Heinz Jöckel, Wolfram Klapper, Andreas Hüttmann
Journal: Blood (2016)
一项在抗 TNF 生物制剂治疗尚未成功的人群中进行的使用两种剂量苏金单抗治疗银屑病的研究
Journal: British Journal of Dermatology (2020)

这篇文章报告了一组英国和爱尔兰共和国的研究人员的研究,这些研究人员旨在确定苏金单抗(一种 IL-17A 抑 制剂)在 TNFa 抑制剂既往治疗无效的中度/重度慢性斑块型银屑病患者中是否安全和有效。 英国和爱尔兰共和国的 53 个皮肤病中心参加了研究。患者被随机分配接受苏金单抗,剂量为 300 mg 或 150 mg,皮下注射,每周一次,持续 4 周,然后每 4 周一次。 使用银屑病面积和严重程度指数 (PASI) 记录患者银屑病的发红程度、厚度和范围,并用于衡量疗效(PASI 分值 降低,即表示症状减轻)。如果患者的 PASI 得分为 75 分,表示其 PASI 分值比最初时下降了 75% 或以上。 总共分析了 233 名患者。300 mg 剂量组的 118 名患者中有 77 名 (65.3%),以及 150 mg 剂量组的 115 名患 者中有 51 名 (44.3%) 在第 16 周达到 PASI 75。 在 72 周治疗后,300 mg 组中 77.1% 在整个研究期间继续接受该治疗的患者达到 PASI 75。在第 16 周也观察 到患者生活质量的改善,并维持至第 72 周。 苏金单抗的安全性与之前的苏金单抗研究一致,尽管观察到一些不良事件(即不良副作用)的发生率更高(如念 珠菌感染,一种真菌感染)。 本研究证明了苏金单抗用于治疗既往 TNFa 抑制剂治疗无效的银屑病患者的疗效和安全性。
Central Role of Semaphorin 3B in a Serum‐Induced Arthritis Model and Reduced Levels in Patients With Rheumatoid Arthritis
Authors: Ana Igea, Tiago Carvalheiro, Beatriz Malvar‐Fernández, Sara Martinez‐Ramos, Carlos Rafael‐Vidal, Ellis Niemantsverdriet, Jezabel Varadé, Andrea Fernández‐Carrera, Norman Jimenez, Trudy McGarry, Angela Rodriguez‐Trillo, Douglas Veale, Ursula Fearon, Carmen Conde, Jose M. Pego‐Reigosa, África González‐Fernández, Kris A. Reedquist, Timothy R. D. J. Radstake, Annette van der Helm‐Van Mil, Samuel García
Journal: Arthritis & Rheumatology (2022)

Semaphorin 3B (Sema3B) decreases the migratory and invasive capacities of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA) and suppresses expression of matrix metalloproteinases. We undertook this study to examine the role of Sema3B in a mouse model of arthritis and its expression in RA patients.Clinical responses, histologic features, and FLS function were examined in wild-type (WT) and Sema3B-/- mice in a K/BxN serum transfer model of arthritis. Protein and messenger RNA expression of Sema3B in mouse joints and murine FLS, as well as in serum and synovial tissue from patients with arthralgia and patients with RA, was determined using enzyme-linked immunosorbent assay, immunoblotting, quantitative polymerase chain reaction, and RNA sequencing. FLS migration was determined using a wound closure assay.The clinical severity of serum-induced arthritis was significantly higher in Sema3B-/- mice compared to WT mice. This was associated with increased expression of inflammatory mediators and increased migratory capacity of murine FLS. Administration of recombinant mouse Sema3B reduced the clinical severity of serum-induced arthritis and the expression of inflammatory mediators. Sema3B expression was significantly lower in the synovial tissue and serum of patients with established RA compared to patients with arthralgia. Serum Sema3B levels were elevated in patients with arthralgia that later progressed to RA, but not in those who did not develop RA; however, these levels drastically decreased 1 and 2 years after RA development.Sema3B expression plays a protective role in a mouse model of arthritis. In RA patients, expression levels of Sema3B in the serum depend on the disease stage, suggesting different regulatory roles in disease onset and progression.
Management and outcomes of extreme preterm birth
Authors: Andrei S Morgan, Marina Mendonça, Nicole Thiele, Anna L David
Journal: BMJ (2022)

### What you need to know Extreme preterm birth, defined as birth before 28 weeks' gestational age (box 1),1 affects about two to five in every 1000 pregnancies, and varies slightly by country and by definitions used. Severe maternal morbidity, including sepsis and peripartum haemorrhage, affects around a quarter of mothers delivering at these gestations.2 For the babies, survival and morbidity rates vary, particularly by gestational age at delivery but also according to other risk factors (birth weight and sex, for example) and by country.34 In this update, we focus on high income countries and provide a broad overview of extreme preterm birth epidemiology, recent changes, and best practices in obstetric and neonatal management, including new treatments such as antenatal magnesium sulphate or changes in delivery management such as delayed cord clamping and placental transfusion. We cover short and long term medical, psychological, and experiential consequences for individuals born extremely preterm, their mothers and families, as well as preventive measures that may reduce the incidence of extreme preterm birth. Box 1 ### Key definitions #### World Health Organization definitions relating to preterm birth #### Preterm #### Moderate to late pretermRETURN TO TEXT
A revised electronic version of RUCAM for the diagnosis of DILI
Authors: Paul H. Hayashi, M. Isabel Lucena, Robert J. Fontana, Einar S. Bjornsson, Guruprasad P. Aithal, Huiman Barnhart, Andres Gonzalez‐Jimenez, Qinghong Yang, Jiezhun Gu, Raul J. Andrade, Jay H. Hoofnagle
Journal: Hepatology (2022)

Abstract Background and Aims Roussel Uclaf Causality Assessment Method (RUCAM) for DILI has been hindered by subjectivity and poor reliability. We sought to improve the RUCAM using data from the Drug‐Induced Liver Injury Network (DILIN) and the Spanish DILI Registry, published literature, and iterative computer modeling. Approach and Results RUCAM criteria were updated, clarified, and computerized. We removed criteria 3 (risk factors) for lack of added value and criteria 4 because we felt it more useful to assess each drug separately. Criteria 6 (drug‐specific risk) was anchored to LiverTox likelihood scores. Iterative testing in subsets of 50–100 single‐agent, nonherbal cases from both registries was done to optimize performance. We used classification tree analysis to establish diagnostic cutoffs for this revised electronic causality assessment method (RECAM) and compared RECAM with RUCAM for correlation with expert opinion diagnostic categories in 194 DILI cases (98 DILIN, 96 Spanish DILI). Area under receiver operator curves for identifying at least probable DILI were the same at 0.89 for RECAM and RUCAM. However, RECAM diagnostic categories have better observed overall agreement with expert opinion (0.62 vs. 0.56 weighted kappa, p = 0.14), and had better sensitivity to detect extreme diagnostic categories (73 vs. 54 for highly likely or high probable, p = 0.02; 65 vs. 48 for unlikely/excluded, p = 0.08) than RUCAM diagnostic categories. Conclusions RECAM is an evidence‐based update that is at least as capable as RUCAM in diagnosing DILI compared with expert opinion but is better than RUCAM at the diagnostic extremes. RECAM’s increased objectivity and clarity will improve precision, reliability, and standardization of DILI diagnosis, but further refinement and validation in other cohorts are needed.
Balancing maximal resection and functional preservation in surgery for low-grade glioma
Authors: Michael A Vogelbaum
Journal: Neuro-Oncology (2022)

The initial management of low-grade gliomas (LGG) has evolved over the past 3 decades. Early debates about the timing of surgical intervention, and in some cases, even whether a procedure to obtain tissue diagnosis should be performed for asymptomatic (incidental) lesions, have been replaced by questions relating to maximizing survival benefit from surgical resection of both symptomatic and incidental lesions suspicious for LGG. Yet, there is recognition that surgically induced impairment of basic neurological functions, such as speech, language, and motor activities should be avoided as they may diminish survival and quality of life (QOL). Fortunately, today’s neurosurgical oncologists can employ specialized tools to both maximize the extent of resection and minimize the consequences of surgical treatment. Publications from the 1990s illustrate the uncertainty that existed at that time regarding the utility of surgery, particularly for incidental lesions. Some neurosurgeons advocated surgery at the time of radiographic diagnosis of an LGG in order to obtain tissue to make a specific diagnosis and to evaluate for markers of biological aggressiveness.1 Others advocated for delaying surgery for patients who did not require surgical intervention to resolve mass effect-related, potentially reversible neurological deficits, noting that the literature to date was largely descriptive and observational only.2 Indeed, some studies that evaluated the timing of treatment after radiographic diagnosis appeared to demonstrate that the patients who had early or late surgery had similar outcomes.3,4
Extracellular matrix modulates T cell clearance of malignant cells in vitro
Authors: Claire Robertson, Aimy Sebastian, Aubree Hinckley, Naiomy D. Rios-Arce, William F. Hynes, Skye A. Edwards, Wei He, Nicholas R. Hum, Elizabeth K. Wheeler, Gabriela G. Loots, Matthew A. Coleman, Monica L. Moya
Journal: Biomaterials (2022)

Despite the success of T cell checkpoint therapies, breast cancers rarely express these immunotherapy markers and are believed to be largely "immune cold" with limited inflammation and immune activation. The reason for this limited immune activation remains poorly understood. We sought to determine whether extracellular matrix substrate could contribute to this limited immune activation. Specifically, we asked whether extracellular matrix could alter T cell cytotoxicity against malignant mammary gland carcinoma cells (MCC) in a setup designed to promote maximal T cell efficacy (i.e., rich media with abundant IL2, high ratio of T cells to MCC). We observed that T cell clearance of MCC varied from 0% in collagen 4 or 6 conditions to almost 100% in fibronectin or vitronectin. Transcriptomics revealed that T cell function was defective in MCC/T cell cocultures on collagen 4 (Col4), potentially corresponding to greater expression of cytokines MCC cultured in this environment. In contrast, transcriptomics revealed an effective, exhausted phenotype on vitronectin. The observation that Col4 induces T cell suppression suggests that targeting tumor-ECM interactions may permit new approaches for utilizing immunotherapy in tumors which do not provoke a strong immune response.
The key role of PSA doubling time in patients treated with salvage radiation therapy after radical prostatectomy: Implications for the extent of radiation and the concomitant use of hormonal therapy
Authors: N. Fossati, J.R. Karnes, S.A. Boorjian, G. Motterle, A. Bossi, T. Kumar, N. Di Muzio, C. Cozzarini, B. Noris Chiorda, E. Mazzone, D. Robesti, G. Gandaglia, D. Bartkowiak, S. Shariat, G. Goldner, S. Joniau, H. Van Poppel, C. Berghen, G. De Meerleer, F. Montorsi, T. Wiegel, A. Briganti
Journal: European Urology (2021)