tbuckley/cabot-search huggingface dataset:
Efficacy and safety of fumaric acid esters in young patients aged 10–17 years with moderate‐to‐severe plaque psoriasis: a randomized, double‐blinded, placebo‐controlled trial*
Authors: H. Hamm, D. Wilsmann‐Theis, A. Tsianakas, T. Gambichler, K. Taipale, J. Lauterbach, U. Freudensprung, C. Makepeace
Journal: British Journal of Dermatology (2020)

Apart from biologics, no systemic drugs are approved in Europe for children with moderate-to-severe psoriasis. Retrospective observational studies have shown promising results for fumaric acid esters (FAE) in this setting.To show superiority of FAE over placebo in terms of treatment response after 20 weeks in children and adolescents aged 10-17 years.In a multicentre, randomized, double-blind, placebo-controlled phase IIIb study, patients aged 10-17 years with moderate-to-severe plaque psoriasis requiring systemic therapy were randomized 2 : 1 to receive FAE (n = 91) or placebo (n = 43) over 20 weeks, followed by an open-label FAE treatment phase. The coprimary endpoints were ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) and Physician's Global Assessment (PGA) score of 0 or 1 (clear or almost clear) at week 20. The study was registered with EudraCT number 2012-000035-82.At week 20, 55% [95% confidence interval (CI) 0·44-0·65] of FAE-treated patients achieved a PASI 75 response vs. 19% (95% CI 0·08-0·33) in the placebo group (absolute difference 36%, 95% CI 0·20-0·53; P < 0·001). In total, 42% (95% CI 0·32-0·53) in the FAE group vs. 7% (95% CI 0·01-0·19) in the placebo group achieved a PGA score of 0 or 1 at week 20 (absolute difference 35%, 95% CI 0·21-0·49; P < 0·001). During the double-blind period, drug-related adverse events occurred more frequently in patients receiving FAE compared with placebo (76% vs. 47%). Gastrointestinal disorders were the most common adverse events.FAE administered over a period of 20 weeks demonstrated a better response than placebo; the difference was statistically significant and clinically meaningful. Application up to 40 weeks was generally well tolerated. However, further studies are required.
Biomaterials developed for facilitating healing outcome after anterior cruciate ligament reconstruction: Efficacy, surgical protocols, and assessments using preclinical animal models
Authors: Xuan He, Ye Li, Jiaxin Guo, Jiankun Xu, Haiyue Zu, Le Huang, Michael Tim-yun Ong, Patrick Shu-hang Yung, Ling Qin
Journal: Biomaterials (2020)
A peptide-based neoantigen vaccine for patients with advanced pancreatic cancer refractory to standard treatment.
Authors: Liu Yang, Shuqing Chen, Fan Mo, Zheling Chen, Jiahong Jiang, Shanshan Zhang, Ning Han, Yunyun Xu, Dongying Ma, Huimin Wang, Xiaojie Guo, Kai Luo, Min Qiu, Qinxue Huang, Liang Liu
Journal: Journal of Clinical Oncology (2021)

e14563 Background: Tumor-specific neoantigens are considered as personalized and potential ultimate targets for cancer immunotherapy. Recently, neoantigen cancer vaccines have been designed to train the patient's immune system to specifically target and kill tumor cells. However, the safety and efficacy of neoantigen vaccines in pancreatic cancer treatment remain poorly understood. Methods: Personalized peptide neoantigen cancer vaccines were successfully designed and manufactured for pancreatic cancers with low tumor mutation burden. Seven patients with advanced pancreatic cancer refractory to standard treatments were enrolled and treated with personalized peptide neoantigen vaccine, iNeo-Vac-P01. Besides the evaluation of the safety and clinical efficacy of iNeo-Vac- P01, pre- and post-vaccination peripheral blood samples were collected to analyze the vaccine’s immunogenicity. Results: For all 7 patients, none sever vaccine-related adverse effects was witnessed. The mean progression free survival, overall survival (OS) and OS associated with vaccine treatment were 3.1, 24.1 and 8.3 months, respectively. For Patient P01, who had a 21-month OS associated with vaccine treatment, the abundance of the TCR clone remarkably increased after vaccination, indicating the potential of iNeo-Vac-P01 to specifically induce a subset of T cells to kill tumor cells. This study also demonstrated that the quantity of IFN-γ in peripheral blood might be a potential biomarker for OS. Conclusions: We believed that it was the first tentative study focused in the application of peptide-based neoantigen cancer vaccine in advanced pancreatic cancer. Promisingly, personalized peptide neoantigen vaccine might provide a new strategy to improve the limited clinical efficacy for pancreatic cancer. Clinical trial information: NCT03645148.
Immunoglobulin A Targets a Unique Subset of the Microbiota in Inflammatory Bowel Disease
Authors: Jason M. Shapiro, Marcel R. de Zoete, Noah W. Palm, Yaro Laenen, Rene Bright, Meaghan Mallette, Kevin Bu, Agata A. Bielecka, Fang Xu, Andres Hurtado-Lorenzo, Samir A. Shah, Judy H. Cho, Neal S. LeLeiko, Bruce E. Sands, Richard A. Flavell, J.C. Clemente
Journal: Cell Host & Microbe (2021)
Venetoclax and dexamethasone synergize with inotuzumab ozogamicin–induced DNA damage signaling in B-lineage ALL
Authors: Hanna Kirchhoff, Uemran Karsli, Caroline Schoenherr, Karin Battmer, Sergej Erschow, Steven R. Talbot, Doris Steinemann, Michael Heuser, Olaf Heidenreich, Denise Hilfiker-Kleiner, Arnold Ganser, Matthias Eder, Michaela Scherr
Journal: Blood (2020)
Порівняльний аналіз якості життя хворих на хронічний біліарний панкреатит після холецистектомії
Authors: N.V. Nazarchuk, L.S. Babinets
Journal: GASTROENTEROLOGY (2020)

При порівняльній оцінці якості життя хворих на хронічний біліарний панкреатит за всіма шкалами SF-36 було доведено, що вірогідно найвищою вона була у групі пацієнтів після лапароскопічної, а найнижчою — після відкритої лапаротомної холецистекомії; р &lt; 0,05. При оцінці якості життя за шкалою болю встановили, що вираженість больового синдрому зменшувалась із тривалістю ХБП (r = 0,31), а загальний стан здоров’я погіршувався (r = –0,24); р &lt; 0,05. Зниження якості життя знаходиться в тісній кореляційній залежності з частотою загострень протягом року (r = 0,83); р &lt; 0,05.
Presentation on Admission and Outcomes in COVID Patients Admitted with AKI
Authors: Richard J. Durrance, Payal Ram, Paul Catella, Demetrios Papademetriou, George N. Coritsidis
Journal: Journal of the American Society of Nephrology (2020)

Background: COVID-19 infection secondary to the SARS-CoV2 virus was defined by the WHO as a global pandemic  While the disease initially affects the respiratory system, a multi-systemic organ dysfunction of varying degrees has been described  Renal failure has been recognized as a significant part of the pathophysiology  Elmhurst Hospital Center (EHC) was described as the 'epicenter of the epicenter' in New York City  Methods: A retrospective chart review was undertaken of COVID positive adult patients (polymerase chain reaction testing of a nasopharyngeal sample) admitted to EHC from 3/7/20 - 4/7/20  Demographics, clinical characteristics, biomarkers, and outcomes were examined  AKI was determined by the KDIGO definition  Exclusion criteria: <18 years old, pregnant, ESRD, patients expired within first 5 days Results: The average age was 59 years, 77 95% were Male;55% had hypertension (HTN), 40% had diabetes (DM)  Hispanics made up the most significant portion of the demographic with 62 05%, followed by Asians (24 1%)  AKI occurred in 44 1% of patients and was associated with HTN ((p=0 011) but not DM (p=0 289)  AKI was associated with an increased use of mechanical ventilation (p<0 001), and increased mortality (p<0 001)  Hypertension (p=0 007), older age (p=0 003), and DM (p=0 018) were significantly associated with mortality  Ethinicity was not associated with mortality (p=0 231)  Admission CPK did not have a significant association with AKI (0 065) or death (p=0 19)  Conclusions: Both HTN and DM are associated with increased mortality  AKI is significantly associated with increased respiratory failure requiring mechanical ventilation and mortality  Diabetes and admission CPK were not associated with AKI
Rampant False Detection of Adaptive Phenotypic Optimization by ParTI-Based Pareto Front Inference
Authors: Mengyi Sun, Jianzhi Zhang
Journal: Molecular Biology and Evolution (2020)

Abstract Organisms face tradeoffs in performing multiple tasks. Identifying the optimal phenotypes maximizing the organismal fitness (or Pareto front) and inferring the relevant tasks allow testing phenotypic adaptations and help delineate evolutionary constraints, tradeoffs, and critical fitness components, so are of broad interest. It has been proposed that Pareto fronts can be identified from high-dimensional phenotypic data, including molecular phenotypes such as gene expression levels, by fitting polytopes (lines, triangles, tetrahedrons, and so on), and a program named ParTI was recently introduced for this purpose. ParTI has identified Pareto fronts and inferred phenotypes best for individual tasks (or archetypes) from numerous data sets such as the beak morphologies of Darwin’s finches and mRNA concentrations in human tumors, implying evolutionary optimizations of the involved traits. Nevertheless, the reliabilities of these findings are unknown. Using real and simulated data that lack evolutionary optimization, we here report extremely high false-positive rates of ParTI. The errors arise from phylogenetic relationships or population structures of the organisms analyzed and the flexibility of data analysis in ParTI that is equivalent to p-hacking. Because these problems are virtually universal, our findings cast doubt on almost all ParTI-based results and suggest that reliably identifying Pareto fronts and archetypes from high-dimensional phenotypic data are currently generally difficult.
Abstract 13732: GCN2 Regulates Vascular Remodeling in the Pathogenesis of Pulmonary Arterial Hypertension
Authors: Maggie M Zhu, Zhiyu Dai, Jingbo Dai, Yi Peng, Youyang Zhao
Journal: Circulation (2019)

Background: Pulmonary arterial hypertension (PAH) is characterized by progressive increase of pulmonary vascular resistance and pulmonary vascular remodeling that result in right heart hypertrophy ...
Promoter-interacting expression quantitative trait loci are enriched for functional genetic variants
Authors: Vivek Chandra, Sourya Bhattacharyya, Benjamin J. Schmiedel, Ariel Madrigal, Cristian Gonzalez-Colin, Stephanie Fotsing, Austin Crinklaw, Gregory Seumois, Pejman Mohammadi, Mitchell Kronenberg, Bjoern Peters, Ferhat Ay, Pandurangan Vijayanand
Journal: Nature Genetics (2020)
Drowning in a tsunami of online resources? Time to take stock and re-invent
Authors: Benjamin Waller, Kati Pasanen
Journal: British Journal of Sports Medicine (2020)

Since lockdown and travel restrictions have been in force, there has been a tsunami of online courses, webinars, congresses and all other forms of learning platforms. The plethora of cancelled congresses led to a rush to put all the content online and deliver it through the computer. All great at saving time, but is trying to apply our old habits to the new norm useful? Let us be completely honest with ourselves, do we pay attention for 6 to 8â€‰hours in an online congress? NO and NO (not that we ever did at a congress either, but there were better distractions often in the form of constructive debate with colleagues). Online congresses cannot provide the same opportunities to meet people during coffee breaks and social activities. Networking, meeting new people and conversations are often more valuable than congress sessions. Ask any student now forced to study at home, do they watch a 1Â½-hour lecture fully while taking endless notes or do they just turn their video off and possibly listen while completing another assignment? Everyone seems busier than ever and trying to push through the COVID-19 challenges, which might be the wrong approach. Let us stop, take a breath and see where â€¦
Эффективность примененияпрепарата Колонзак у пациентов с различными клиническими вариантами синдрома раздраженного кишечника
Authors: D.T. Janelidze
Journal: GASTROENTEROLOGY (2020)

Актуальность. На сегодняшний день этиология симптомов синдрома раздраженного кишечника (СРК) полностью не установлена. Отсутствие четкого понимания патогенетических механизмов развития того или иного функционального заболевания кишечника, в том числе СРК, с учетом наличия разнообразных структурно-морфологических нарушений в стенке кишки диктует необходимость поиска новых препаратов, действие которых будет направлено на разные звенья патогенеза кишечных заболеваний. Цель исследования — изучить эффективность и безопасность применения препарата Колонзак у пациентов с различными клиническими вариантами синдрома раздраженного кишечника. Материалы и методы. Обследованы 42 пациента с верифицированным диагнозом СРК (14 — СРК тип 1; 14 — СРК тип 2; 9 — СРК тип 3; 5 — СРК тип 4) в возрасте от 25 до 45 лет (средний возраст 35,0 ± 1,7 года). У всех пациентов с СРК органическая кишечная патология была исключена при проведении колоноскопии. ­Диагноз СРК установлен в соответствии с Римскими критериями IV. Кроме модификации образа жизни и соблюдения правил питания в зависимости от типа СРК, все пациенты (независимо от варианта СРК) получали средство Колонзак по 1 капсуле 2 раза в день, утром и вечером перед едой 30 дней. Все пациенты заполняли опросник по оценке степени тяжести симптомов СРК до и после курса лечения. Полученные результаты были статистически обработаны при помощи программ Excel 2017 (Microsoft) и Statistica 13. Результаты. Проведенное исследование показало, что Колонзак, содержащий пробиотические штаммы бифидобактерий, пребиотик инулин и масляную кислоту, можно рассматривать как безопасное, хорошо переносимое и высокоэффективное средство для пациентов с разными вариантами СРК. У пациентов с СРК применение препарата Колонзак сопровождалось статистически значимым улучшением состояния. Выводы. Наше исследование подтвердило клиническую эффективность средства Колонзак как мультикомпонентного колонопротектора при СРК. Полученные результаты позволяют рекомендовать широкое применение препарата Колонзак у пациентов с разными вариантами СРК.
Implantable multifunctional black phosphorus nanoformulation-deposited biodegradable scaffold for combinational photothermal/ chemotherapy and wound healing
Authors: Chencheng Xue, Linawati Sutrisno, Menghuan Li, Wei Zhu, Yang Fei, Changhuang Liu, Xuan Wang, Kaiyong Cai, Yan Hu, Zhong Luo
Journal: Biomaterials (2020)
Cross sectional investigation of a COVID-19 outbreak at a London Army barracks: Neutralising antibodies and virus isolation
Authors: Hannah Taylor, William Wall, David Ross, Roshni Janarthanan, Liyang Wang, Felicity Aiano, Joanna Ellis, Robin Gopal, Nick Andrews, Monika Patel, Angie Lackenby, Richard Myers, Mary E Ramsay, J. Yimmy Chow, Maria Zambon, Shamez N Ladhani
Journal: The Lancet Regional Health - Europe (2020)
Intense Diffuse Uptake of 68Ga-FAPI-04 in the Breasts Found by PET/CT in a Patient With Advanced Nasopharyngeal Carcinoma
Authors: Li-juan Wang, Yin Zhang, Hu-bing Wu
Journal: Clinical Nuclear Medicine (2020)

The physiological uptake of 68Ga-FAPI-04 due to the change of the internal environment is little known. We report the case of a 45-year-old woman who was highly suspected to have advanced nasopharyngeal carcinoma. 18F-FDG and 68Ga-FAPI-04 PET/CT was performed for evaluating the disease. Both PET and CT with different tracers detected the primary nasopharyngeal carcinoma and metastases in right neck lymph nodes, liver, and bones. To our surprise, intense diffuse uptake of 68Ga-FAPI-04 was found in both breasts, which might be due to the hormone stimulation because the patient received 68Ga-FAPi-04 PET/CT just at the period of ovulation.
Commercial immunoglobulin products contain cross-reactive but not neutralizing antibodies against SARS-CoV-2
Authors: Terrie S. Ahn, Brandon Han, Paul Krogstad, Chantana Bun, Lisa A. Kohn, Maria I. Garcia-Lloret, Robert Damoiseaux, Manish J. Butte
Journal: Journal of Allergy and Clinical Immunology (2020)
JNK2, a Newly-Identified SERCA2 Enhancer, Augments an Arrhythmic [Ca <sup>2+</sup> ] <sub>SR</sub> Leak-Load Relationship
Authors: Jiajie Yan, Dan J. Bare, Jaime DeSantiago, Weiwei Zhao, Yiming Mei, Zhenhui Chen, Kenneth Ginsburg, R. John Solaro, Beata M. Wolska, Donald M. Bers, S.R. Wayne Chen, Xun Ai
Journal: Circulation Research (2020)

We recently discovered pivotal contributions of stress kinase JNK2 (c-Jun N-terminal kinase isoform 2) in increased risk of atrial fibrillation through enhanced diastolic sarcoplasmic reticulum (SR) calcium (Ca2+) leak via RyR2 (ryanodine receptor isoform 2). However, the role of JNK2 in the function of the SERCA2 (SR Ca2+-ATPase), essential in maintaining SR Ca2+ content cycling during each heartbeat, is completely unknown.To test the hypothesis that JNK2 increases SERCA2 activity SR Ca2+ content and exacerbates an arrhythmic SR Ca2+ content leak-load relationship.We used confocal Ca2+ imaging in myocytes and HEK-RyR2 (ryanodine receptor isoform 2-expressing human embryonic kidney 293 cells) cells, biochemistry, dual Ca2+/voltage optical mapping in intact hearts from alcohol-exposed or aged mice (where JNK2 is activated). We found that JNK2, but not JNK1 (c-Jun N-terminal kinase isoform 1), increased SERCA2 uptake and consequently elevated SR Ca2+ content load. JNK2 also associates with and phosphorylates SERCA2 proteins. JNK2 causally enhances SERCA2-ATPase activity via increased maximal rate, without altering Ca2+ affinity. Unlike the CaMKII (Ca2+/calmodulin-dependent kinase II)-dependent JNK2 action in SR Ca2+ leak, JNK2-driven SERCA2 function was CaMKII independent (not prevented by CaMKII inhibition). With CaMKII blocked, the JNK2-driven SR Ca2+ loading alone did not significantly raise leak. However, with JNK2-CaMKII-driven SR Ca2+ leak present, the JNK2-enhanced SR Ca2+ uptake limited leak-induced reduction in SR Ca2+, normalizing Ca2+ transient amplitude, but at a higher arrhythmogenic SR Ca2+ leak. JNK2-specific inhibition completely normalized SR Ca2+ handling, attenuated arrhythmic Ca2+ activities, and alleviated atrial fibrillation susceptibility in aged and alcohol-exposed myocytes and intact hearts.We have identified a novel JNK2-induced activation of SERCA2. The dual action of JNK2 in CaMKII-dependent arrhythmic SR Ca2+ leak and a CaMKII-independent uptake exacerbates atrial arrhythmogenicity, while helping to maintain normal levels of Ca2+ transients and heart function. JNK2 modulation may be a novel therapeutic target for atrial fibrillation prevention and treatment.
Emergence of a non vaccine-cognate enterovirus A71 genotype C1 in mainland China
Authors: Hanri Zeng, Lina Yi, Xiaoli Chen, Huiqiong Zhou, Huanying Zheng, Jing Lu, Fen Yang, Caixia Li, Ling Fang, Xin Zhang, Xu Jing, Jie Wu, Hui Li
Journal: Journal of Infection (2020)
Safety of immune checkpoint inhibitor rechallenge after discontinuation for grade ≥2 immune-related adverse events in patients with cancer
Authors: Marion Allouchery, Thomas Lombard, Mickael Martin, Franck Rouby, Marion Sassier, Celia Bertin, Marina Atzenhoffer, Ghada Miremont-Salame, Marie-Christine Perault-Pochat, Mathieu Puyade
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Safety of rechallenge of immune checkpoint inhibitor (ICI) after grade ≥2 immune-related adverse events (irAEs) leading to ICI discontinuation remains unclear. Methods All adverse drug reactions involving at least one ICI reported up to December 31, 2019 were extracted from the French pharmacovigilance database. Patients were included if they experienced at least one grade ≥2 irAE resulting in ICI discontinuation, with subsequent ICI rechallenge. The primary outcome was the recurrence of at least one grade ≥2 irAE in these patients after ICI rechallenge. Results We included 180 patients: 61.1% were men (median age of 66 years), 43.9% had melanoma and 78.9% were receiving anti-programmed cell death 1. First ICI discontinuation was related to 191 irAEs. After ICI rechallenge, 38.9% of the patients experienced at least one grade ≥2 irAE. Among them, 70.0% experienced the same irAE, 25.7% a distinct irAE, and 4.3% both the same and a distinct irAE. Lower recurrence rates of irAEs were associated with rechallenge with the same ICI treatment (p=0.02) or first endocrine irAEs (p=0.003). Gastrointestinal irAEs were more likely to recur (p=0.007). The median duration from ICI discontinuation to rechallenge and the severity of the initial irAE did not predict recurrent irAEs after ICI rechallenge (p=0.53 and p=0.40, respectively). Conclusions In this study, 61.1% of the patients who discontinued ICI treatment for grade ≥2 irAEs experienced no recurrent grade ≥2 irAEs after ICI rechallenge. Although ICI rechallenge appears to be safe under close monitoring, it should always be discussed balancing usefulness of rechallenge, patient comorbidities and risk of recurrence of first irAE(s). Due to inherent bias associated with pharmacovigilance studies, further prospective studies are needed to assess risk factors that may influence patient outcomes after ICI rechallenge.
Microplastic Contamination of Seafood Intended for Human Consumption: A Systematic Review and Meta-Analysis
Authors: Evangelos Danopoulos, Lauren C. Jenner, Maureen Twiddy, Jeanette M. Rotchell
Journal: Environmental Health Perspectives (2020)

BACKGROUND: Microplastics (MPs) have contaminated all compartments of the marine environment including biota such as seafood; ingestion from such sources is one of the two major uptake routes identified for human exposure.OBJECTIVES: The objectives were to conduct a systematic review and meta-analysis of the levels of MP contamination in seafood and to subsequently estimate the annual human uptake.METHODS: MEDLINE, EMBASE, and Web of Science were searched from launch (1947, 1974, and 1900, respectively) up to October 2020 for all studies reporting MP content in seafood species.Mean, standard deviations, and ranges of MPs found were collated.Studies were appraised systematically using a bespoke risk of bias (RoB) assessment tool.RESULTS: Fifty studies were included in the systematic review and 19 in the meta-analysis.Evidence was available on four phyla: mollusks, crustaceans, fish, and echinodermata.The majority of studies identified MP contamination in seafood and reported MP content <1 MP=g, with 26% of studies rated as having a high RoB, mainly due to analysis or reporting weaknesses.Mollusks collected off the coasts of Asia were the most heavily contaminated, coinciding with reported trends of MP contamination in the sea.According to the statistical summary, MP content was 0-10:5 MPs=g in mollusks, 0:1-8:6 MPs=g in crustaceans, 0-2:9 MPs=g in fish, and 1 MP=g in echinodermata.Maximum annual human MP uptake was estimated to be close to 55,000 MP particles.Statistical, sample, and methodological heterogeneity was high.DISCUSSION: This is the first systematic review, to our knowledge, to assess and quantify MP contamination of seafood and human uptake from its consumption, suggesting that action must be considered in order to reduce human exposure via such consumption.Further high-quality research using standardized methods is needed to cement the scientific evidence on MP contamination and human exposures.
Evolution of blood–brain barrier in brain diseases and related systemic nanoscale brain-targeting drug delivery strategies
Authors: Liang Han, Chen Jiang
Journal: Acta Pharmaceutica Sinica B (2020)

Blood-brain barrier (BBB) strictly controls matter exchange between blood and brain, and severely limits brain penetration of systemically administered drugs, resulting in ineffective drug therapy of brain diseases. However, during the onset and progression of brain diseases, BBB alterations evolve inevitably. In this review, we focus on nanoscale brain-targeting drug delivery strategies designed based on BBB evolutions and related applications in various brain diseases including Alzheimer's disease, Parkinson's disease, epilepsy, stroke, traumatic brain injury and brain tumor. The advances on optimization of small molecules for BBB crossing and non-systemic administration routes (e.g., intranasal treatment) for BBB bypassing are not included in this review.