bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disulfiram inhibits liver fibrosis in rats by suppressing hepatic stellate cell activation and viability
Authors: Yang Xiao-Mei , Wu Zheng , Wang Xiaoqi , Zhou Yaoqi , Zhu Lei , Li Dongxue , Nie Hui-Zhen , Wang Ya-Hui , Li Jun , Ma Xueyun 
Published: July 2022

Abstract
Background
Liver fibrosis is a wound-healing response to chronic injury, featuring with excess accumulation of extracellular matrix secreted by the activated hepatic stellate cells (HSC). Disulfiram (DSF), also known as Antabuse, has been used for the treatment of alcohol addiction and substance abuse. Recently, overwhelming studies had revealed anti-cancer effects of DSF in multiple cancers, including liver cancer. But the actual effects of DSF on liver fibrosis and liver function remain unknown.

Methods
In this study, we evaluated the effects of low-dose DSF in CCl4- and Bile Duct Ligation (BDL)—induced hepatic fibrosis rat models. Cell proliferation was detected by using the Cell-Light™ EdU Apollo®567 Cell Tracking Kit. Cell apoptosis was analyzed using a TdT-mediated dUTP nick end labeling (TUNEL) kit, viability was measured with Cell Counting Kit-8(CCK8). Relative mRNA expression of pro-fibrogenic was assessed using quantitative RT-PCR. The degree of liver fibrosis, activated HSCs, were separately evaluated through Sirius Red-staining, immunohistochemistry and immunofluorescence. Serum alanine aminotransferase (ALT) and asparagine aminotransferase (AST) activities were detected with ALT and AST detecting kits using an automated analyzer.

Results
Liver fibrosis was distinctly attenuated while liver functions were moderately ameliorated in the DSF-treated group. Activation and proliferation of primary rat HSCs isolated from rat livers were significantly suppressed by low-dose DSF. DSF also inhibited the viability of in vitro cultured rat or human HSC cells dose-dependently but had no repressive role on human immortalized hepatocyte THLE-2 cells. Interestingly, upon DSF treatment, the viability of LX-2 cells co-cultured with THLE-2 was significantly inhibited, while that of THLE-2 co-cultured with LX-2 was increased. Further study indicated that HSCs apoptosis was increased in DSF/CCl4-treated liver samples. These data indicated that DSF has potent anti-fibrosis effects and protective effects toward hepatocytes and could possibly be repurposed as an anti-fibrosis drug in the clinic.

Conclusions
DSF attenuated ECM remodeling through suppressing the transformation of quiet HSCs into proliferative, fibrogenic myofibroblasts in hepatic fibrosis rat models. DSF provides a novel approach for the treatment of liver fibrosis.
Measuring learning that is hard to measure: using the PECSL model to evaluate implicit smart learning
Authors: Lister Pen 
Published: July 2022

AbstractThis paper explores potential ways of evaluating the implicit learning that may be present in autonomous smart learning activities and environments, reflecting on prior phenomenographic research into smart learning activities positioned as local journeys in urban connected public spaces. Implicit learning is considered as intrinsic motivation, value and richer engagement by participants, demonstrating levels of experience complexity, interpreted as levels of implicit learning. The paper reflects on ideas for evaluating implicit smart learning through planning for experience complexity in the context of a pedagogical model, the Pedagogy of Experience Complexity for Smart Learning (PECSL), developed from the research. By supplementing this model with further conceptual mechanisms to describe experience complexity as surface to deep learning alongside cognitive domain taxonomy equivalences, implicit smart learning might be evaluated in broad flexible ways to support the design of more effective and engaging activities. Examples are outlined placing emphasis on learner generated content, learner-directed creative learning and supporting dialogue and reflection, attempting to illustrate how implicit learning might manifest and be evaluated.
Rational coordination regulation in carbon-based single-metal-atom catalysts for electrocatalytic oxygen reduction reaction
Authors: Cui Xun , Gao Likun , Lu Cheng-Hsin , Ma Rui , Yang Yingkui , Lin Zhiqun 
Published: July 2022

AbstractSingle-metal-atom catalysts (SMACs) have garnered extensive attention for various electrocatalytic applications, owing to their maximum atom-utilization efficiency, tunable electronic structure, and remarkable catalytic performance. In particular, carbon-based SMACs exhibit optimal electrocatalytic activity for the oxygen reduction reaction (ORR) which is of paramount importance for several sustainable energy conversion and generation technologies, such as fuel cells and metal-air batteries. Despite continuous endeavors in developing various advanced carbon-based SMACs for electrocatalytic ORR, the rational regulation of coordination structure and thus the electronic structure of carbon-based SMACs remains challenging. In this review, we critically examine the role of coordination structure, including local coordination structure (i.e., metal atomic centers and the first coordination shell) and extended local coordination structure (i.e., the second and higher coordination shells), on the rational design of carbon-based SMACs for high-efficiency electrocatalytic ORR. Insights into the relevance between coordination structures and their intrinsic ORR activities are emphatically exemplified and discussed. Finally, we also propose the major challenges and future perspectives in the rational design of advanced carbon-based SMACs for electrocatalytic ORR. This review aims to emphasize the significance of coordination structure and deepen the insightful understanding of structure-performance relationships.
Solar and geomagnetic activity dependence of 150-km echoes observed by the Equatorial Atmosphere Radar in Indonesia
Authors: Yokoyama Tatsuhiro , Takagi Rieko , Yamamoto Mamoru 
Published: July 2022

AbstractThe occurrence characteristics of 150-km echoes in low-latitude regions are studied using the Equatorial Atmosphere Radar (EAR) in Indonesia. The long-term observation of the 150-km echoes by the EAR enables us to study the occurrence characteristics of 150-km echoes statistically. It is shown that the occurrence rate of the 150-km echoes observed by the EAR shows a semiannual variation with two peaks in solstices and a negative correlation with both the EUV flux and $$\Sigma$$
Σ
Kp index, that is, the solar and the geomagnetic activity. Geomagnetic activity correlates with the occurrence rate of 150-km echoes observed one day after when the $$\Sigma$$
Σ
Kp was measured. However, the occurrence rate is always low during the high solar activity period regardless of the geomagnetic activity. While the seasonal variation and the solar activity dependence of the occurrence of 150-km echoes are consistent with previous studies, this is the first time a negative correlation with geomagnetic activity is reported.
Graphical Abstract
Long head of the biceps intra-articular tenotomy using needle arthroscopy under local anesthesia: preliminary results and technical note
Authors: Rosso Claudio , Grezda Kushtrim , Heuberer Philipp R. 
Published: July 2022

Abstract
Purpose
Arthroscopic isolated biceps tenotomy is a procedure successfully performed in patients with degenerative rotator cuff tears which offers good clinical results. With this article, we describe the technique of biceps tenotomy with needle arthroscopy in local anesthesia and the results of first patients treated from 2018.

Methods
Thirteen patients with irreparable rotator cuff tear treated with arthroscopic needle biceps tenotomy under local anesthesia were included. Constant score and active/passive flexion were recorded preoperatively and at 3 months postoperatively.

Results
The average age of the patients was 71 ± 7 year old. All the patients were available for the follow-up. The Constant score significantly improved from pre- to postoperatively (44 ± 8.9 to 63.1 ± 14.2, p < 0.05). Active flexion improved from preoperatively 115 ± 24° to 145 ± 31° postoperatively (p < 0.05), while passive flexion did not significantly improve.

Conclusion
This technique can be safely performed in the elderly patient with irreparable rotator cuff tears and pain refractory to conservative measures.
Clinical and radiographic outcomes following transcrestal maxillary sinus floor elevation with injectable xenogenous bone substitute in gel form: a prospective multicenter study
Authors: Lombardi Teresa , Lamazza Luca , Bernardello Fabio , Ziętek Grzegorz , Stacchi Claudio , Troiano Giuseppe 
Published: July 2022

Abstract
Purpose
To investigate clinical and radiographic outcomes of transcrestal maxillary sinus floor elevation performed with an injectable xenograft in gel form, analyzing general, local and surgical variables possibly influencing the results.

Methods
Patients with residual crestal height < 5 mm underwent transcrestal sinus floor elevation with xenograft in gel form to allow the placement of a single implant. Simultaneous implant placement was performed when primary stability was ≥ 15 Ncm. Graft height was measured immediately after surgery (T0) and after 6 months of healing (T1). Univariate and multivariate regression models were built to assess associations between clinical variables with implant survival and graft height at T1.

Results
71 patients underwent transcrestal sinus floor elevation and 54 implants were simultaneously placed. Delayed implant placement (at T1) was possible in 5 cases out of 17 (29.4%), whereas in 12 patients (70.6%) implant insertion was not possible or required additional sinus grafting. Implant survival rate, with a follow-up varying from 12 to 32 months after loading, was 100%. Mean pre-operative bone height was 3.8 ± 1.0 mm, at T0 was 13.9 ± 2.2 mm and at T1 was 9.9 ± 2.8 mm. Bone height at T1 was negatively influenced by membrane perforation at surgery (p = 0.004) and positively influenced by immediate implant insertion (p < 0.001).

Conclusions
Transcrestal sinus floor elevation performed with injectable xenograft gel resulted in 100% implant survival rate. However, immediate implant insertion seems a crucial factor to preserve vertical bone gain: one-stage technique seems to be the most predictable approach to optimize clinical outcomes with this approach.
Trial registration clinicaltrials.gov, NCT05305521. Registered 31 March 2022—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT05305521.
Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as risk factors for mortality in Peruvian adults with chronic kidney disease
Authors: Umeres-Francia Gianfranco Eddú , Rojas-Fernández María Valentina , Herrera-Añazco Percy , Benites-Zapata Vicente Aleixandre 
Published: July 2022

Abstract
Objective
To assess the association between the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) with all-cause mortality in Peruvian patients with chronic kidney disease (CKD) attending a tertiary hospital.

Methods
We conducted a retrospective cohort study in adults with CKD in stages 1–5. The outcome variable was mortality and as variables of exposure to NLR and PLR. Both ratios were categorized as high with a cutoff point of 3.5 and 232.5, respectively. We carried out a Cox regression model and calculated crude and adjusted hazard ratios (HR) with their 95% confidence interval (95% CI).

Results
We analyzed 343 participants with a mean age of 78.3 (± 11.9) years and 62.9% (n = 216) men. The median follow-up time was 2.45 years (2.08–3.08), and the frequency of deaths was 17.5% (n = 60). The mortality of patients with high NLR was 28% compared to 15.7% of the group with normal NLR, and the mortality was 35.7% in those with high PLR and 15.6% in those with normal PLR. In the crude analysis, the high NLR and PLR were significantly associated with all-cause mortality (HR = 2.01; 95% CI 1.11–3.66) and (HR = 2.58; 95% CI 1.31–5.20). In the multivariate model, after adjusting for age, sex, serum creatinine, albumin and hemoglobin, the high NLR and PLR remained as independent risk factors for all-cause mortality (aHR = 1.97; 95% CI 1.05–3.69) and (aHR = 2.62; 95% CI 1.25–5.51), respectively.

Conclusion
Our study suggests the relationship between high NLR and PLR with all-cause mortality in patients with CKD.
Cannabis-only use in the USA: prevalence, demographics, use patterns, and health indicators
Authors: Carlini Beatriz H. , Schauer Gillian L. 
Published: July 2022

Abstract
Background
The prevalence of adults who consume cannabis while abstaining from other substances is not known in the USA. This study used nationally representative data to estimate the prevalence and explore the demographic characteristics, cannabis use behaviors, and self-reported health of US adults with past 30-day cannabis-only use, as compared with adults who used cannabis as well as other substances.

Methods
Data came from adults 18 years and older who responded to the 2017 or 2018 National Survey on Drug Use and Health and reported past 30-day cannabis use (n = 12,143). Cannabis-only use was defined as past 30-day cannabis use with no past 30-day use of other substances (alcohol, tobacco, other illicit substances, non-prescribed controlled medications). Weighted frequencies and 95% confidence intervals (CI) were computed for all sociodemographic and cannabis-related variables, overall, and across the two categories of cannabis consumers, stratified by age.

Results
The prevalence of past 30-day cannabis-only use among US adults was 0.9% (95% CI: 0.8, 1.0) and varied by age (2.0% of 18–25 years old; 0.7% of 26–49 year olds, and 0.6% of those ≥ 50 years). Among adults with any past 30-day cannabis use, 8.4% (95% CI: 7.6, 9.2; n = 980) reported cannabis-only use. Age was significantly associated with past 30-day cannabis-only use, with adults 18–25 years and 26–49 years having higher odds of cannabis-only use compared with older adults. Past year cannabis dependence was lowest among cannabis-only consumers aged ≥ 50 years (0.2%; 95% CI: 0.1, 0.5) and highest among young adult cannabis and other substance consumers (16.7%; 95% CI: 15.3, 18.2). Past year prevalence of any mental illness was generally similar across cannabis use groups and by age.

Conclusions
The prevalence of adult cannabis-only use in the US is low — most cannabis consumers report using other substances in the past 30 days as well. While cannabis-only use among older adults is rare, it does not appear to be accompanied by a high prevalence of dependence. These findings should guide future research and policymaking.
Ventilator-induced lung injury results in oxidative stress response and mitochondrial swelling in a mouse model
Authors: Joelsson Jon Petur , Asbjarnarson Arni , Sigurdsson Snaevar , Kricker Jennifer , Valdimarsdottir Bryndis , Thorarinsdottir Holmfridur , Starradottir Eir , Gudjonsson Thorarinn , Ingthorsson Saevar , Karason Sigurbergur 
Published: July 2022

Abstract
Background
Mechanical ventilation is a life-saving therapy for critically ill patients, providing rest to the respiratory muscles and facilitating gas exchange in the lungs. Ventilator-induced lung injury (VILI) is an unfortunate side effect of mechanical ventilation that may lead to serious consequences for the patient and increase mortality. The four main injury mechanisms associated with VILI are: baro/volutrauma caused by overstretching the lung tissues; atelectrauma, caused by repeated opening and closing of the alveoli resulting in shear stress; oxygen toxicity due to use of high ratio of oxygen in inspired air, causing formation of free radicals; and biotrauma, the resulting biological response to tissue injury, that leads to a cascade of events due to excessive inflammatory reactions and may cause multi-organ failure. An often-overlooked part of the inflammatory reaction is oxidative stress. In this research, a mouse model of VILI was set up with three tidal volume settings (10, 20 and 30 mL/kg) at atmospheric oxygen level. Airway pressures and heart rate were monitored and bronchoalveolar lavage fluid (BALF) and lung tissue samples were taken.

Results
We show a correlation between increased inflammation and barrier failure, and higher tidal volumes, evidenced by increased IL-6 expression, high concentration of proteins in BALF along with changes in expression of adhesion molecules. Furthermore, swelling of mitochondria in alveolar type II cells was seen indicating their dysfunction and senescence-like state. RNA sequencing data present clear increases in inflammation, mitochondrial biogenesis and oxidative stress as tidal volume is increased, supported by degradation of Keap1, a redox-regulated substrate adaptor protein.

Conclusions
Oxidative stress seems to be a more prominent mechanism of VILI than previously considered, indicating that possible treatment methods against VILI might be identified by impeding oxidative pathways.
The consequence of the credit risk on the financial performance in light of COVID-19: Evidence from Islamic versus conventional banks across MEA region
Authors: Ahmed Hussien Mohsen , El-Halaby Sherif Ismail , Soliman Hebatallah Ahmed 
Published: July 2022

Abstract
Purpose
The increased number of nonperforming loans (NPLs) during COVID-19 pandemic has interrogated the robustness of banks and stability of the whole banking segment. We examine the impact of credit risk (CR) on financial performance (FP) by comparing Islamic banks (IBs) to conventional banks (CBs). We also investigate the influence of COVID-19 on this association.

Design/methodology/approach
Our sample includes the largest 200 banks across 15 countries from the Middle East and the Africa (MEA) region over a four-year period (2018–2021). Panel ordinary least squares (OLS) with fixed and random effects were used.

Findings
We find a negative association between NPLs and FP for IBs and CBs. We reveal that COVID-19 is partially mediated the association between NPLs and FP in case of the whole sample and separated sample of CBs while not in case of IBs.

Originality
The evidence of CR and FP on samples of financial sector across MEA region has not been studied in the era of COVID-19 as far as we know.

Research limitations/implications
This study contributes to the knowledge of the risk and financial performance during the crisis nexus and provides information that is valued to bankers, academics, managers and regulators for policy formulation.
Modification of the Association Between Frequent Aspirin Use and Ovarian Cancer Risk: A Meta-Analysis Using Individual-Level Data From Two Ovarian Cancer Consortia
Authors: Hurwitz Lauren M. , Townsend Mary K. , Jordan Susan J. , Patel Alpa V. , Teras Lauren R. , Lacey James V. , Doherty Jennifer A. , Harris Holly R. , Goodman Marc T. , Shvetsov Yurii B. , Modugno Francesmary , Moysich Kirsten B. , Robien Kim , Prizment Anna , Schildkraut Joellen M. , Berchuck Andrew , Fortner Renée T. , Chan Andrew T. , Wentzensen Nicolas , Hartge Patricia , Sandler Dale P. , O'Brien Katie M. , Anton-Culver Hoda , Ziogas Argyrios , Menon Usha , Ramus Susan J. , Pearce Celeste Leigh , Wu Anna H. , White Emily , Peters Ulrike , Webb Penelope M. , Tworoger Shelley S. , Trabert Britton 
Published: July 2022

PURPOSE Frequent aspirin use has been associated with reduced ovarian cancer risk, but no study has comprehensively assessed for effect modification. We leveraged harmonized, individual-level data from 17 studies to examine the association between frequent aspirin use and ovarian cancer risk, overall and across subgroups of women with other ovarian cancer risk factors. METHODS Nine cohort studies from the Ovarian Cancer Cohort Consortium (n = 2,600 cases) and eight case-control studies from the Ovarian Cancer Association Consortium (n = 5,726 cases) were included. We used Cox regression and logistic regression to assess study-specific associations between frequent aspirin use (≥ 6 days/week) and ovarian cancer risk and combined study-specific estimates using random-effects meta-analysis. We conducted analyses within subgroups defined by individual ovarian cancer risk factors (endometriosis, obesity, family history of breast/ovarian cancer, nulliparity, oral contraceptive use, and tubal ligation) and by number of risk factors (0, 1, and ≥ 2). RESULTS Overall, frequent aspirin use was associated with a 13% reduction in ovarian cancer risk (95% CI, 6 to 20), with no significant heterogeneity by study design ( P = .48) or histotype ( P = .60). Although no association was observed among women with endometriosis, consistent risk reductions were observed among all other subgroups defined by ovarian cancer risk factors (relative risks ranging from 0.79 to 0.93, all P-heterogeneity > .05), including women with ≥ 2 risk factors (relative risk, 0.81; 95% CI, 0.73 to 0.90). CONCLUSION This study, the largest to-date on aspirin use and ovarian cancer, provides evidence that frequent aspirin use is associated with lower ovarian cancer risk regardless of the presence of most other ovarian cancer risk factors. Risk reductions were also observed among women with multiple risk factors, providing proof of principle that chemoprevention programs with frequent aspirin use could target higher-risk subgroups.
Trends in the Quality of Evidence Supporting FDA Drug Approvals: Results from a Literature Review
Authors: Brown Beatrice L. , Mitra-Majumdar Mayookha , Joyce Krysten , Ross Murray , Pham Catherine , Darrow Jonathan J. , Avorn Jerry , Kesselheim Aaron S. 
Published: July 2022

Abstract
Context: New drug approvals in the United States must be supported by substantial evidence from “adequate and well-controlled” trials. The Food and Drug Administration (FDA) has flexibility in how it applies this standard.
Methods: The authors conducted a systematic literature review of studies evaluating the design and outcomes of the key trials supporting new drug approvals in the United States. They extracted data on the trial characteristics, endpoint types, and expedited regulatory pathways.
Findings: Among 48 publications eligible for inclusion, 30 covered trial characteristics, 23 covered surrogate measures, and 30 covered regulatory pathways. Trends point toward less frequent randomization, double-blinding, and active controls, with variation by drug type and indication. Surrogate measures are becoming more common but are not consistently well correlated with clinical outcomes. Drugs approved through expedited regulatory pathways often have less rigorous trial design characteristics.
Conclusions: The characteristics of trials used to approve new drugs have evolved over the past two decades along with greater use of expedited regulatory pathways and changes in the nature of drugs being evaluated. While flexibility in regulatory standards is important, policy changes can emphasize high-quality data collection before or after FDA approval.
International Reference Pricing in the Context of US Drug Policy
Authors: Frank Richard , Conti Rena M. , Gruber Jonathan 
Published: July 2022

Abstract
International reference prices (IRP), also called external reference prices, are widely used across developed nations. IRP uses the prices paid in other countries to either inform negotiations with the pharmaceutical industry or as a cap on market prices. The authors review the application of IRP to cap the prices of negotiated outcomes in the context of US proposals for changing the way prescription drug prices are established for the Medicare program. They examine the economic, political, and administrative issues associated with the use of IRP, and they summarize the evidence on the impacts of IRP.