bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and effectiveness of RBD-specific polyclonal equine F(ab′)2 fragments for the treatment of hospitalized patients with severe Covid-19 disease: a retrospective cohort study
Authors: Farizano Salazar Diego H. , Achinelli Fernando , Colonna Mariana , Perez Lucía , Giménez Analía A. , Ojeda Maria Alejandra , Miranda Puente Susana N. , Negrette Lía Sánchez , Cañete Florencia , Martelotte Ibarra Ornela I. , Sanguineti Santiago , Spatz Linus , Goldbaum Fernando A. , Massa Carolina , Rivas Marta , Pichel Mariana , Hiriart Yanina , Zylberman Vanesa , Gallego Sandra , Konigheim Brenda , Fernandez Francisco , Deprati Matías , Roubicek Ian , Giunta Diego H. , Nannini Esteban , Lopardo Gustavo , Belloso Waldo H. 
Published: April 2022

AbstractPassive immunotherapy has been evaluated as a therapeutic alternative for patients with COVID-19 disease. Equine polyclonal immunotherapy for COVID-19 (EPIC) showed adequate safety and potential efficacy in a clinical trial setting and obtained emergency use authorization in Argentina. We studied its utility in a real world setting with a larger population.MethodsWe conducted a retrospective cohort study at “Hospital de Campaña Escuela-Hogar” in Corrientes, Argentina, to assess safety and effectiveness of EPIC in hospitalized adults with severe COVID-19 pneumonia. Primary endpoints were 28-days all-cause mortality and safety. Mortality and improvement in modified WHO clinical scale at 14 and 21 days were secondary endpoints. Potential confounder adjustment was made by logistic regression weighted by the inverse of the probability of receiving the treatment (IPTW) and doubly robust approach.ResultsClinical records of 395 exposed (EPIC) and 446 non-exposed (Controls) patients admitted between November 2020 and April 2021 were analyzed. Median age was 58 years and 56.8% were males. Mortality at 28 days was 15.7% (EPIC) vs. 21.5% (Control). After IPTW adjustment the OR was 0.66 (95 % CI: 0.46 - 0.96), P= 0.03. The effect was more evident in the subgroup who received two EPIC doses (complete treatment, n=379), OR: 0.58 (95% CI 0.39 to 0.85), P=0.005. Overall and serious adverse events were not significantly different between groups.ImportanceIn this retrospective cohort study, EPIC showed adequate safety and effectiveness in the treatment of hospitalized patients with severe SARS-CoV-2 disease.
The effect of neoadjuvant therapy on PD-L1 expression and CD8 lymphocyte density in non-small cell lung cancer
Authors: Zens Philipp , Bello Corina , Scherz Amina , Gunten Michael von , Ochsenbein Adrian , Schmid Ralph A , Berezowska Sabina 
Published: April 2022

AbstractPD-L1 expression is the routine clinical biomarker for the selection of patients to receive immunotherapy in non-small cell lung cancer (NSCLC). However, the application and best timing of immunotherapy in the resectable setting is still under investigation. We aimed to study the effect of chemotherapy on PD-L1 expression and tumor infiltrating lymphocytes (TIL), which is to date still poorly understood. This retrospective, single-centre study cohort comprised 96 consecutive patients with NSCLC resected in 2000-2016 after neoadjuvant therapy, including paired chemo-naïve specimens in 57 cases. A biologically matched control cohort of 114 primary resected cases was included. PD-L1 expression, CD8+ TIL density and tertiary lymphoid structures were assessed on whole slides and correlated with clinico-pathological characteristics and survival.Seven/57 and 12/57 cases had lower respectively higher PD-L1 expressions after neoadjuvant therapy. Most cases (n = 38) had no changes in PD-L1 expression and the majority of these showed PD-L1 < 1% in both samples (23/38 [60.5%]). CD8+ TILs density was significantly higher after chemotherapy (p = 0.031) in paired resections. Neoadjuvant cases showed no difference in PD-L1 expression or CD8+ TILs density compared to the chemotherapy naïve control cohort. In univariable analyses, higher CD8+ TILs density, higher numbers of tertiary lymphoid structures but not PD-L1 expression were significantly associated with better survival. Increased PD-L1 expression after neoadjuvant chemotherapy was visually associated with worse 5-year survival, lacking statistical significance probably due to the low number of cases. PD-L1 expression is mostly unchanged after neoadjuvant chemotherapy. However, an increase of PD-L1 expression after neoadjuvant therapy could be associated with worse survival.
The cognitive phenotype of juvenile absence epilepsy and its heritability: An investigation of patients and unaffected siblings
Authors: Caciagli Lorenzo , Ratcliffe Corey , Xiao Fenglai , van Graan Louis A. , Trimmel Karin , Vollmar Christian , Centeno Maria , Duncan John S. , Thompson Pamela J. , Baxendale Sallie , Koepp Matthias J. , Wandschneider Britta 
Published: April 2022

ABSTRACTObjectiveThe cognitive profile of juvenile absence epilepsy (JAE) remains uncharacterized. This study aimed to: (i) elucidate the neuropsychological profile of JAE; (ii) identify familial cognitive traits, by investigating unaffected JAE siblings; (iii) determine whether cognitive traits across the idiopathic generalized epilepsy (IGE) spectrum are shared or syndrome-specific, by comparing JAE to JME; and (iv) identify associations between cognitive abilities and clinical characteristics.MethodsWe investigated 123 participants: 23 patients with JAE, 16 unaffected siblings of JAE patients, 45 healthy controls, and 39 patients with JME, who underwent a comprehensive neuropsychological test battery including measures within four cognitive domains: attention/psychomotor speed, language, learning, and executive function. We also correlated clinical measures with cognitive performance data to decode effects of age at onset and duration of epilepsy.ResultsPatients with JAE performed worse than controls across tests of psychomotor speed, language, learning and executive function. Patients and siblings were similarly impaired on language measures of verbal comprehension, phonemic fluency, and semantic fluency compared to controls. Receiver operating characteristic curves indicated successful discrimination of patients with JAE and siblings from controls via linguistic measures. Individuals with JME also presented with multidomain cognitive impairment and had worse response inhibition than those with JAE. Across all patients, those with older age at onset had better performance on psychomotor speed and executive function tests.SignificanceJAE is associated with wide-ranging cognitive difficulties that encompass domains reliant on frontal lobe processing, including language, attention, and executive function. JAE siblings demonstrate shared impairment with patients on linguistic measures, indicative of a familial trait. Executive function subdomains may be differentially affected across the IGE spectrum. Cognitive abilities are detrimentally modulated by an early age at seizure onset.KEY POINTSJAE presents with multidomain cognitive impairment involving language, attention/ psychomotor speed, executive function, and learning.Impaired language is common to people with JAE and their unaffected siblings, suggestive of a familial trait (endophenotype).Response inhibition is worse in JME than JAE, indicating distinct cognitive profiles across the IGE spectrum.Early age at epilepsy onset is associated with worse cognitive performance in JAE and JME.
Low knowledge about hepatitis B prevention among pregnant women in the Democratic Republic of the Congo
Authors: Thahir Sahal , Tulenko Samantha E. , Ngimbi Patrick , Ntambua Sarah , Matondo Jolie , Mwandagalirwa Kashamuka , Tabala Martine , Kaba Didine , Yotebieng Marcel , Parr Jonathan B. , Thompson Peyton 
Published: April 2022

AbstractInfants infected perinatally with hepatitis B (HBV) are at the highest risk of developing chronic hepatitis and associated sequelae. Prevention of mother-to-child transmission (PMTCT) of HBV requires improved screening and awareness of the disease. This study evaluated existing HBV knowledge among pregnant mothers (n = 280) enrolled in two HBV screening studies in two urban maternity centers in Kinshasa, Democratic Republic of the Congo. All mothers responded to three knowledge questions upon study enrollment. Baseline levels of knowledge related to HBV transmission, treatment, and symptoms were low across all participants; 60% of participants responded “I don’t know” to all questions. HBV-positive women who participated in both studies (n= 46) were asked the same questions during both studies and showed improved knowledge after screening and treatment, despite no formal educational component in either study. These findings highlight the need for intensified education initiatives in highly endemic areas to improve PMTCT efforts.
The PAF1 complex cell autonomously promotes oogenesis in Caenorhabditis elegans
Authors: Kubota Yukihiro , Ota Natsumi , Takatsuka Hisashi , Unno Takuma , Onami Shuichi , Sugimoto Asako , Ito Masahiro 
Published: April 2022

AbstractThe RNA polymerase II‐associated factor 1 complex (PAF1C) is a protein complex that consists of LEO1, RTF1, PAF1, CDC73, and CTR9, and has been shown to be involved in RNA polymerase II‐mediated transcriptional and chromatin regulation. Although it has been shown to regulate a variety of biological processes, the precise role of the PAF1C during germ line development has not been clarified. In this study, we found that reduction in the function of the PAF1C components, LEO‐1, RTFO‐1, PAFO‐1, CDC‐73, and CTR‐9, in Caenorhabditis elegans affects oogenesis. Defects in oogenesis were also confirmed using an oocyte maturation marker, OMA‐1::GFP. While four to five OMA‐1::GFP‐positive oocytes were observed in wild‐type animals, their numbers were significantly decreased in pafo‐1 mutant and leo‐1(RNAi), pafo‐1(RNAi), and cdc‐73(RNAi) animals. Expression of a functional PAFO‐1::mCherry transgene in the germline significantly rescued the oogenesis‐defective phenotype of the pafo‐1 mutants, suggesting that expression of the PAF1C in germ cells is required for oogenesis. Notably, overexpression of OMA‐1::GFP partially rescued the oogenesis defect in the pafo‐1 mutants. Based on our findings, we propose that the PAF1C promotes oogenesis in a cell‐autonomous manner by positively regulating the expression of genes involved in oocyte maturation.
Prognostic impact of worsening of esophageal varices after balloon‐occluded retrograde transvenous obliteration
Authors: Shinkai Kazuma , Sakamori Ryotaro , Yamada Ryoko , Tahata Yuki , Nozaki Yasutoshi , Matsumoto Kengo , Tawara Seiichi , Fukuda Kazuto , Yoshida Yuichi , Tanaka Satoshi , Ito Toshifumi , Doi Yoshinori , Iio Sadaharu , Sakakibara Mitsuru , Nakanishi Fumihiko , Kodama Takahiro , Hikita Hayato , Tatsumi Tomohide , Takehara Tetsuo 
Published: April 2022

AbstractBackground and AimBalloon‐occluded retrograde transvenous obliteration (BRTO) is widely performed for treating gastric varices (GVs). However, worsening of esophageal varices (EVs) can be observed after BRTO. This study aimed to investigate the impact of EV worsening on prognosis after BRTO.MethodsOverall, 258 patients who underwent initial BRTO for GV treatment between January 2004 and May 2019 at 12 institutions were retrospectively registered.ResultsTechnical success was achieved in 235 patients (91.1%). Based on the exclusion criteria, 37 patients were excluded, and 198 were evaluated. The cumulative worsening rates of EVs at 1, 2, and 3 years were 39.0%, 59.4%, and 68.4%, respectively. In the univariate Cox proportional hazards model, sex, EV size, history of EV treatment, left gastric vein dilatation, platelet count, aspartate transaminase (AST), alanine aminotransferase (ALT), total bilirubin, albumin, albumin–bilirubin score, prothrombin time‐international normalized ratio, fibrosis‐4 index, AST to platelet ratio index, and spleen width were significantly associated with worsening of EV after BRTO. Multivariate analysis showed that sex (adjusted hazard ratio [aHR] 1.72; 95% confidence interval [CI] 1.03–2.86; P = 0.04), left gastric vein dilatation (aHR 1.90; 95% CI 1.17–3.10; P = 0.01), ALT (aHR 1.01; 95% CI 1.00–1.03; P = 0.02), albumin (aHR 0.61; 95% CI 0.43–0.87; P < 0.01), and spleen width (aHR 1.02; 95% CI 1.01–1.03; P < 0.01) were independent risk factors for worsening of EV after BRTO. Patients with EV worsening within 1 year after BRTO had a significantly worse prognosis than the other patients (P = 0.007).ConclusionsEarly worsening of EV after BRTO was associated with poor prognosis after BRTO.
Gender differences in science, technology, engineering and maths uptake and attainment in post‐16 education
Authors: McDool Emily , Morris Damon 
Published: April 2022

AbstractThe underrepresentation of women in Science, Technology, Engineering and Maths (STEM) occupations is a world‐wide phenomenon. The UK is simultaneously encountering a shortage of STEM skills. While gender imbalances in STEM study in higher education and A‐level study are widely documented, gender imbalances are apparent in vocational post‐16 education, though the existence and causes of these imbalances have received little attention. This paper uses administrative data to explore the extent of gender imbalances in STEM qualifications attempted and achieved in vocational post‐16 education routes. Gender differentials in the uptake of vocational STEM qualifications are much starker than they are in A‐levels and the roles of ability, socio‐economic status and school characteristics in explaining gender differentials differ with the education route taken, though their power in explaining these gaps is limited.
When healing turns into killing – the pathophysiology of pancreatic and hepatic fibrosis
Authors: Ferdek Pawel E. , Krzysztofik Daria , Stopa Kinga B. , Kusiak Agnieszka A. , Paw Milena , Wnuk Dawid , Jakubowska Monika A. 
Published: April 2022

AbstractDisorders such as pancreatic or hepatic fibrosis are a cruel reminder that disruption of the delicate physiological balance could result in severe pathological consequences. Fibrosis is usually associated with chronic diseases and manifests itself as excessive deposition of the extracellular matrix, which gradually leads to the replacement of the cellular components by fibrotic lesions, significantly compromising normal tissue functions. The main cellular mediators of fibrosis are different populations of tissue fibroblasts, predominantly hepatic and pancreatic stellate cells in the liver and pancreas, respectively. These cells undergo a phenotypic switch in response to (bio)chemical or physical stimuli and acquire a myofibroblast‐like phenotype characterised by increased contractile and adhesive properties, elevated expression of certain cytoskeletal and membrane proteins, and prominent production of extracellular matrix components. In the past few decades, a substantial scientific effort has been undertaken to investigate the pathogenesis of fibrosis. Here, cellular mechanisms of hepatic and pancreatic fibrosis, their aetiological factors, associated diseases and prospective therapies are discussed. New therapies against fibrosis are likely to be focused on regulation of hepatic/pancreatic stellate cell physiology as well as normalisation of the organ mechanostasis.
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Chitosan nanoparticles containing fusion protein (Hspx–PPE44–EsxV) and resiquimod adjuvant (HPERC) as a novel booster vaccine for Mycobacterium tuberculosis
Authors: Hoseinpur Rasul , Hasani Alka , Baradaran Behzad , Abdolalizadeh Jalal , Amini Yousef , Salehi Roya , Samadi Kafil Hossein , Azizian Khalil , Memar Mohammad Yousef , Gholizadeh Pourya , Hasani Akbar 
Published: April 2022

This study attempted to explore the immunogenicity of chitosan nanoparticles containing fusion protein (Hspx–PPE44–EsxV; HPE) and resiquimod adjuvant (HPERC) in BALB/c mice. HPE was initially expressed in E. coli BL21 cells. HPE and resiquimod adjuvant were then encapsulated in chitosan nanoparticles (HPERC). One group of mice were subcutaneously vaccinated on days 0, 14, and 28 with HPERC, and the other group was primed with bacilli Calmette-Guérin (BCG) on day 0 and then boosted with HPERC on days 14 and 28. Two weeks after the last injection, IFN-γ, IL-4, and IL-17 in spleen cell culture supernatants, and IgG2a and IgG1 titers in sera were measured. HPERC size was 130.84 ± 12.08 nm ( n = 5). Zeta potential of HPERC was 29 ± 4 mv. The highest IFN-γ concentration was detected in BCG-primed mice that were boosted with HPERC. In addition, IL-17 production was significantly increased in all groups compared with that of control, except in those that received nanoparticle (NP), adjuvant (ADJ), NP/ADJ, and fusion protein (Hspx–PPE44–EsxV) (HPE). Comparison of IFN-γ and IL-4 concentration determined that Th1 was activated in BCG-primed and HPERC-boosted group in comparison to the other groups. No significant difference in concentration of IL-4 was observed between groups receiving HPERC and BCG-primed and HPERC-boosted group in comparison to group BCG. Concentrations of IgG2a and IgG1 also increased compared to the control group and the rate of IgG2a was higher compared to IgG1. Chitosan containing HPERC vaccine could induce a high level of specific cytokines in mice. The group of mice which first received BCG and then HPERC as booster vaccine could produce significant amounts of IFN-γ, IL-17, and IgG2a.
“We need to build a better bridge”: findings from a multi-site qualitative analysis of opportunities for improving opioid treatment services for youth
Authors: Marchand Kirsten , Fogarty Oonagh , Pellatt Katrina Marie , Vig Kayly , Melnychuk Jordan , Katan Christina , Khan Faria , Turuba Roxanne , Kongnetiman Linda , Tallon Corinne , Fairbank Jill , Mathias Steve , Barbic Skye 
Published: April 2022

Abstract
Background
Adolescence and young adulthood is an important period for substance use initiation and related harms. In the context of the ongoing opioid crisis, the risks for youth (ages 16–29) who use opioids are particularly heightened. Despite recommendations to adopt a developmentally appropriate and comprehensive approach to reduce opioid-related harms among youth, data continue to show that youth are not adequately engaged in opioid treatments and encounter many barriers. The aim of this study is to identify youth-centered opportunities for improving opioid treatment services.

Methods
This paper reports multi-site qualitative findings from youth participating in the ‘Improving Treatment Together’ project, a community-based participatory project being conducted in British Columbia and Alberta, two western Canadian provinces that have been dramatically impacted by the opioid crisis. Qualitative data were collected during three workshops with youth who used opioids and accessed opioid treatment services in the prior 12 months. These workshops were conducted in three communities following the core elements of human-centered co-design. A multi-site qualitative analysis was conducted to identify within- and between-site themes surrounding youths’ needs for improving opioid treatment service experiences and outcomes.

Results
Three overarching needs themes were identified from across the communities. The first reflected youths’ difficulties finding and staying connected to opioid treatment services, with the overarching need theme suggesting opportunities to reduce organizational and systems-related barriers to care, such as waiting times and wider information about service availability. The second area of need was rooted in youths’ feelings of judgment when accessing services. Consequently, opportunities to increase respectful and empathic interactions were the overarching need. The final theme was more nuanced across communities and reflected opportunities for an individualized approach to opioid treatment services that consider youths’ unique basic safety, social, and health needs.

Conclusions
This study identifies fundamental directions for the operationalization and implementation of youth-centered opioid treatment services. These directions are contextualized in youths’ lived experiences accessing services in their local communities, with overarching themes from across sites strengthening their transferability to other settings.
On the role of stablecoins in cryptoasset pricing dynamics
Authors: Kristoufek Ladislav 
Published: April 2022

AbstractWe examine the interactions between stablecoins, Bitcoin, and a basket of altcoins to uncover whether stablecoins represent the investors’ demand for trading and investing into cryptoassets or rather play a role as boosting mechanisms during cryptomarkets price rallies. Using a set of instruments covering the standard cointegration framework as well as quantile-specific and non-linear causality tests, we argue that stablecoins mostly reflect an increasing demand for investing in cryptoassets rather than serve as a boosting mechanism for periods of extreme appreciation. We further discuss some specificities of 2017, even though the dynamic patterns remain very similar to the general behavior. Overall, we do not find support for claims about stablecoins being bubble boosters in the cryptoassets ecosystem.
Characterization of Candida species isolated from vulvovaginal candidiasis by MALDI-TOF with in vitro antifungal susceptibility profiles
Authors: Aslani Narges , Kokabi Roya , Moradi Fatemeh , Abbasi Kiana , Vaseghi Narges , Afsarian Mohammad Hosein 
Published: April 2022

Background and Purpose: Vulvovaginal candidiasis (VVC) is an opportunistic infection due to Candida species, one of the most common genital tract diseases among reproductive-age women. The present study aimed to investigate the prevalence of VVC among non-pregnant women and identify the epidemiology of the involved Candida species with the evaluation of antifungal susceptibilities.
Materials and Methods: Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was performed to identify Candida species isolated from the genital tract of 350 non-pregnant women. Moreover, antifungal susceptibility testing was performed according to the Clinical and Laboratory Standards Institute broth microdilution method guidelines (M27-A3 and M27-S4).
Results: Vaginal swab cultures of 119 (34%) women yielded Candida species. Candida albicans was the most frequently isolated species (68%), followed by Candida glabrata (19.2%). Voriconazole was the most active drug against all tested isolates showing an MIC50/MIC90 corresponding to 0.016/0.25 µg/mL, followed by posaconazole (0.031/1 µg/mL). Overall, resistance rates to fluconazole, itraconazole, and voriconazole were2.4%, 4.8% and, 0.8% respectively. However, posaconazole showed potent in vitro activity against all tested isolates.
Conclusion: Results of the current study showed that for the effectual therapeutic outcome of candidiasis, accurate identification of species, appropriate source control, suitable antifungal regimens, and improved antifungal stewardship are highly recommended for the management and treatment of infection with Candida, like VVC.