bluuebunny/crossref_metadata_2025_split huggingface dataset:
EXACT Trial: Results of the Phase 1 Dose-Escalation Study
Authors: Povsic Thomas J. , Henry Timothy D. , Traverse Jay H. , Anderson R. David , Answini Geoffrey A. , Sun Benjamin C. , Arnaoutakis George J. , Boudoulas Konstantinos D. , Williams Adam R. , Dittrich Howard C. , Tarka Elizabeth A. , Latter David A. , Ohman E. Magnus , Peterson Mark W. , Byrnes Dawn , Pepine Carl J. , DiCarli Marcelo F. , Crystal Ronald G. , Rosengart Todd K. , Mokadam Nahush A. 
Published: July 2023

BACKGROUND:
New therapies are needed for patients with refractory angina. Encoberminogene rezmadenovec (XC001), a novel adenoviral-5 vector coding for all 3 major isoforms of VEGF (vascular endothelial growth factor), demonstrated enhanced local angiogenesis in preclinical models; however, the maximal tolerated dose and safety of direct epicardial administration remain unknown.

METHODS:

In the phase 1 portion of this multicenter, open-label, single-arm, dose-escalation study, patients with refractory angina received increasing doses of encoberminogene rezmadenovec (1×10
9
, 1×10
10
, 4×10
10
, and 1×10
11
viral particles) to evaluate its safety, tolerability, and preliminary efficacy. Patients had class II to IV angina on maximally tolerated medical therapy, demonstrable ischemia on stress testing, and were angina-limited on exercise treadmill testing. Patients underwent minithoracotomy with epicardial delivery of 15 0.1-mL injections of encoberminogene rezmadenovec. The primary outcome was safety via adverse event monitoring over 6 months. Efficacy assessments included difference from baseline to months 3, 6 (primary), and 12 in total exercise duration, myocardial perfusion deficit using positron emission tomography, angina class, angina frequency, and quality of life.

RESULTS:

From June 2, 2020 to June 25, 2021, 12 patients were enrolled into 4 dosing cohorts with 1×10
11
viral particle as the highest planned dose. Seventeen serious adverse events were reported in 7 patients; none were related to study drug. Six serious adverse events in 4 patients were related to the thoracotomy, 3 non–serious adverse events were possibly related to study drug. The 2 lowest doses did not demonstrate improvements in total exercise duration, myocardial perfusion deficit, or angina frequency; however, there appeared to be improvements in all parameters with the 2 higher doses.

CONCLUSIONS:

Epicardial delivery of encoberminogene rezmadenovec via minithoracotomy is feasible, and up to 1×10
11
viral particle appears well tolerated. A dose response was observed across 4 dosing cohorts in total exercise duration, myocardial perfusion deficit, and angina class. The highest dose (1×10
11
viral particle) was carried forward into phase 2.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT04125732.
Evaluation of Reanalysis Estimates of Precipitation, Radiation, and Temperature over Benin (West Africa)
Authors: Bodjrenou René , Cohard Jean-Martial , Hector Basile , Lawin Emmanuel Agnidé , Chagnaud Guillaume , Danso Derrick Kwadwo , N’tcha M’po Yekambessoun , Badou Félicien , Ahamide Bernard 
Published: July 2023

Abstract
In West Africa, climatic data issues, especially availability and quality, remain a significant constraint to the development and application of distributed hydrological modeling. As alternatives to ground-based observations, reanalysis products have received increasing attention in recent years. This study aims to evaluate three reanalysis products, namely, ERA5, Water and Global Change (WATCH) Forcing Data (WFD) ERA5 (WFDE5), and MERRA-2, from 1981 to 2019 to determine their ability to represent four hydrological climates variables over a range of space and time scales in Benin. The variables from the reanalysis products are compared with point station databased metrics Kling–Gupta efficiency (KGE), mean absolute error (MAE), correlation, and relative error in precipitation annual (REPA). The results show that ERA5 presents a better correlation for annual mean temperature (between 0.74 and 0.90) than do WFDE5 (0.63–0.78) and MERRA-2 (0.25–0.65). Both ERA5 and WFDE5 are able to reproduce the observed upward trend of temperature (0.2°C decade−1) in the region. We noted a systematic cold bias of ∼1.3°C in all reanalyses except WFDE5 (∼0.1°C). On the monthly time scale, the temperature of the region is better reproduced by ERA5 and WFDE5 (KGE ≥ 0.80) than by MERRA-2 (KGE < 0.5). At all time scales, WFDE5 produces the best MAE scores for longwave (LW) and shortwave (SW) radiation, followed by ERA5. WFDE5 also provides the best estimates for the annual precipitation (REPA ∈ ]−25, 25[ and KGE ≥ 50% at most stations). ERA5 produces similar results, but MERRA-2 performs poorly in all the metrics. In addition, ERA5 and WFDE5 reproduce the bimodal rainfall regime in southern Benin, unlike MERRA-2, but all products have too many small rainfall events.
Body mass index is not associated with time on veno-venous extracorporeal membrane oxygenation or in-hospital mortality
Authors: Roden-Foreman Jordin S. , Foreman Michael L. , Monday Kara , Lingle Kaitlyn , Blough Britton , Safa Mohamad M. , Schwartz Gary 
Published: July 2023

Morbid obesity, as characterized by BMI, is often utilized as an exclusion criterion for VV-ECMO because of presumed poor prognosis and technically complex cannulation. However, the “obesity paradox” suggests obesity may be protective during critical illness, and BMI does not capture variations in body type, adiposity, or fluid balance. This study examines relationships between BMI and patient outcomes. Adult VV-ECMO patients with BMI ≥ 35 kg/m2 admitted January 2012 to June 2021 were identified from an institutional registry. BMI and outcomes were analyzed with Mann-Whitney U tests and Pearson correlations with Bayesian post-hoc analyses. 116 of 960 ECMO patients met inclusion criteria. Median (Q1, Q3) BMI was 42.3 (37.3, 50.8) and min, max of 35.0, 87.8 with 9.0 (5.0, 15.5) ECMO days. BMI was not significantly correlated with ECMO days (r = −0.102; p = .279). Bayesian analyses showed moderate evidence against BMI correlating with ECMO days. In-hospital mortality (27%) was significantly associated with ECMO days ( p = .014) but not BMI ( p = .485). In this cohort of high-BMI patients, BMI was not associated with survival or time on ECMO. BMI itself should not be used as an exclusion criterion for VV-ECMO.
Penehyclidine hydrochloride protects against lipopolysaccharide-induced acute lung injury by promoting the PI3K/Akt pathway
Authors: Weng Junting , Liu Danjuan , Shi Bingbing , Chen Min , Weng Shuoyun , Guo Rongjie , Fu Chunjin 
Published: July 2023

Introduction Acute lung injury (ALI) attracted attention among physicians because of its high mortality. We aimed to determine whether the phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt) pathway is involved in the protective effects of penehyclidine hydrochloride (PHC) against lipopolysaccharide (LPS)-induced ALI. Methods H&E staining was used to observed pathological changes in the lung tissues. ELISA was used to evaluate the concentration of inflammatory mediators in the bronchoalveolar lavage fluid (BALF). White-light microscopy was performed to observe the TUNEL-positive nuclei. The viability of NR8383 alveolar macrophages was determined by using CCK-8. The levels of MPO, MDA, SOD, and GSH-Px were analyzed using ELISA kits. Western blotting was used to evaluate the ERS-associated protein levels and the phosphorylation of PI3K and Akt. Results PHC administration defended against LPS-induced histopathological deterioration and increased pulmonary edema and lung injury scores, while all of these beneficial effects were inhibited by LY. In addition, PHC administration mitigated oxidative stress as indicated by decreases in lung myeloperoxidase (MPO) and malondialdehyde (MDA) concentrations, and increases in glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) concentrations. It also alleviated LPS-induced inflammation. PHC administration attenuated apoptosis-associated protein levels, improved cell viability, and decreased the number of TdT-mediated dUTP Nick-End Labeling (TUNEL)-positive cells. Furthermore, PHC inhibited ERS-associated protein levels. Meanwhile, the protection of PHC against inflammation, oxidative stress, apoptosis, and ERS was inhibited by LY. Moreover, PHC administration increased PI3K and Akt phosphorylation, indicating that the upregulation of the PI3K/Akt pathway, while this pathway was inhibited by LY. Conclusion PHC significantly activates the PI3K/Akt pathway to ameliorate the extent of damage to pulmonary tissue, inflammation, oxidative stress, apoptosis, and ERS in LPS-induced ALI.
Ocular surface in posterior segment surgery
Authors: Coassin Marco , Arrigo Alessandro , Ricci Federico , Rosa Raffaella , Gattegna Roberto , Pupino Alessandro , Del Castillo Josè Manuel Benitez , Bonini Stefano 
Published: July 2023

Nowadays, the technological breakthroughs of mini-invasive vitreo-retinal surgery improved the perioperative management and the outcomes of millions of patients. The most common procedures include pars plana vitrectomy, episcleral surgery, intravitreal injections, and laser photocoagulation. Potential sight and non-sight-threatening side effects have been reported during the follow-up period. Ocular surface disbalance can be induced by the aforementioned procedures, resulting in mild to severe ocular discomfort symptoms. This condition may recognize different causes such as pre-existing or concomitant diseases of the external eye, the surgical procedure damage of the anatomical or physiological structures of the ocular surface, the prolonged side effects induced by the chronic topical treatment that may be toxic to the external eye. In addition to the most frequent dry eye-related signs and symptoms, subconjunctival haemorrhages, corneal epithelium damage, partial loss of corneal sensitivity or changes in corneal nerve density could postoperatively affect our patients. In conclusion, any surgical trauma directed to the posterior segment of the eye may cause the loss of the ocular surface homeostasis. Ophthalmologists should not only recognise and treat, but possibly prevent, all patients’ symptoms that could manifest in the postoperative time.
The Potential Impact of ChatGPT on Education: Using History as a Rearview Mirror
Authors: Wang (王梦倩) Mengqian , Guo (郭文革) Wenge 
Published: July 2023

Highlights This review compares generative artificial intelligence with five representative educational technologies in history and concludes that AI technology can become a knowledge producer and thus can be utilized as educative AI to enhance teaching and learning outcomes. From a historical perspective, each technological breakthrough has affected education by changing how symbols are represented and how knowledge is carried. The emergence of new educational technology is always accompanied by doubt, vigilance, and rejection from the traditional community. The new educational technology, generative artificial intelligence, interacts with the old, creating an increasingly complex ecology of educational technology. Three suggestions are proposed for adjusting the education system: first, promoting small-scale, individualized, and conversational teaching in schools; second, developing teachers’ and students’ digital literacy in a multi-curricula system; and third, conducting research on grading and classification standards for the application of AI in education.
Effect of Autologous Conditioned Plasma Injections in Patients With Knee Osteoarthritis
Authors: Korpershoek Jasmijn V. , Vonk Lucienne A. , Filardo Giuseppe , Kester Esmee C. , van Egmond Nienke , Saris Daniël B.F. , Custers Roel J.H. 
Published: July 2023

Background: Autologous conditioned plasma (ACP) is a commercially available platelet concentrate with promising results from clinical trials. Purpose: To evaluate the clinical outcome after 3 consecutive injections of ACP in patients with knee osteoarthritis (OA) and study the influence of ACP composition and different patient factors as predictors of treatment effect. Study Design: Case series; Level of evidence, 4. Methods: This prospective case series included 260 patients (307 knees) who received ACP treatment for knee OA. The mean patient age was 51 ± 10 years. Improvement up to 12 months’ follow-up was measured using the Knee injury and Osteoarthritis Outcome Score (KOOS). ACP composition was analyzed in 100 patients. The predictive value of age, sex, history of knee trauma, Kellgren-Lawrence OA grade, body mass index, and ACP composition was evaluated using generalized estimating equations. Results: The mean overall KOOS improved from 38 ± 14 at baseline to 45 ± 18 at 3 months, 45 ± 18 at 6 months, and 43 ± 18 at 12 months (all P < .05); 40% of patients achieved an improvement above the minimal clinically important difference (MCID) of 8 after 6 months and 33% after 12 months. The variation in ACP composition did not correlate with KOOS ( P > .05). Older age led to a greater clinical benefit (β = 0.27; P = .05), whereas bilateral treatment predicted worse outcomes (β = –5.6; P < .05). Conclusion: The improvement in KOOS after treatment with ACP did not reach the MCID in most study patients. Older age was a predictor for better outcomes. The composition of ACP varied between patients but did not predict outcomes within the evaluated range. The study findings show the limited benefit of ACP treatment for knee OA and call for caution with routine use in clinical practice.
Knowledge and Compliance With Standard Precautions Among Nurses
Authors: Ghabayen Fares , ALBashtawy Mohammed , Abdelkader Raghad Hussein , Jarrah Samiha , Eshah Nidal , Abdalrahim Asem , Saifan Ahmad , Alkhawaldeh Abdullah , Rayan Ahmad , Ayed Ahmad , Al-Amer Rasmieh , Mohammad Khitam Ibrahem , Al-Dwaikat Tariq , Omari Omar Al , ALBashtawy Sa'd , ALBashtawy Bayan , Dameery Khloud Al 
Published: July 2023

Introduction The spread of microorganisms is caused by direct or indirect contact, respiratory droplets, and airborne transmission. Knowledge and compliance with standard precautions are crucial in preventing infection in the hospital. Objectives To assess the level of knowledge and compliance with standard precautions among registered nurses who work in military hospitals and the factors affecting compliance with standard precautions. Methods A descriptive cross-sectional study was conducted. Four hundred and eight registered nurses at three Jordanian Royal Medical Services hospitals completed an online self-report questionnaire using a convenience sampling technique. The statistical package for social sciences (SPSS) version 25 was used to analyze the data. Results The level of knowledge of standard precautions among nurses was excellent, with an overall mean score of 15.59 ± 2.22 out of 20; around half (54%) of them had an excellent level. Nurses’ compliance with standard precautions was intermediate, with an overall mean score of 59.65 ± 14.57 out of 80. Forty-seven percent of nurses had a high degree of compliance. Compliance with standard precautions was correlated positively with age, working experience in years, total knowledge score, training in standard precautions, and availability of personal protective equipment, and negatively with exposure to sharp injuries. Conclusion Nurses play a key role in preventing and managing hospital infections through their responsibility for a large proportion of patient treatment and care. Therefore, efforts should be made to improve nurses’ perceptions of the basic elements of standard precautions. Even so, results showed that compliance with standard precautions was intermediate. This highlights the need to take the necessary measures to raise the level of compliance. Even so, results showed that compliance with standard precautions was intermediate. This highlights the need to take the necessary measures to raise the level of compliance.
Advancing research on teams and team effectiveness in implementation science: An application of the Exploration, Preparation, Implementation, Sustainment (EPIS) framework
Authors: McGuier Elizabeth A. , Kolko David J. , Stadnick Nicole A. , Brookman-Frazee Lauren , Wolk Courtney Benjamin , Yuan Christina T. , Burke C. Shawn , Aarons Gregory A. 
Published: July 2023

Background Effective teams are essential to high-quality healthcare. However, teams, team-level constructs, and team effectiveness strategies are poorly delineated in implementation science theories, models, and frameworks (TMFs), hindering our understanding of how teams may influence implementation. The Exploration, Preparation, Implementation, Sustainment (EPIS) framework is a flexible and accommodating framework that can facilitate the application of team effectiveness approaches in implementation science. Main Text We define teams and provide an overview of key constructs in team effectiveness research. We describe ways to conceptualize different types of teams and team constructs relevant to implementation within the EPIS framework. Three case examples illustrate the application of EPIS to implementation studies involving teams. Within each study, we describe the structure of the team and how team constructs influenced implementation processes and outcomes. Conclusions Integrating teams and team constructs into the EPIS framework demonstrates how TMFs can be applied to advance our understanding of teams and implementation. Implementation strategies that target team effectiveness may improve implementation outcomes in team-based settings. Incorporation of teams into implementation TMFs is necessary to facilitate application of team effectiveness research in implementation science.
A frog peptide provides new strategies for the intervention against skin wound healing
Authors: Li Chao , Fu Zhe , Jin Tao , Liu Yixiang , Liu Naixin , Yin Saige , Wang Zhuo , Huang Yubing , Wang Yinglei , Zhang Yingxuan , Li Jiayi , Wu Yutong , He Li , Tang Jing , Wang Ying , Yang Xinwang 
Published: July 2023

Abstract
Background
Amphibian derived pro-healing peptides as molecular probes might provide a promising strategy for development of drug candidates and elucidation of cellular and molecular mechanisms of skin wound healing. A novel skin amphibian peptide, OA-RD17, was tested for modulation of cellular and molecular mechanisms associated with skin wound healing.

Methods
Cell scratch, cell proliferation, trans-well, and colony formation assays were used to explore the pro-healing ability of peptide OA-RD17 and microRNA-632 (miR-632). Then, the therapeutic effects of OA-RD17 and miR-632 were assessed in mice, diabetic patient ex vivo skin wounds and SD rats. Moreover, hematoxylin and eosin (H&E), enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, and immunofluorescence staining were performed to detect skin wound tissue regeneration, inflammatory factors expression, and macrophage polarization. Finally, RNA sequencing, molecular docking, co-localization, dual luciferase reporter, real-time quantitative reverse transcription PCR (RT-qPCR), and Western blotting were used to explore the mechanism of OA-RD17 and miR-632 on facilitating skin wound healing.

Results
The non-toxic peptide (OA-RD17) promoted macrophage proliferation and migration by activating MAPK and suppressed inflammation by inhibiting NF-κB. In keratinocytes, OA-RD17 inhibited excessive inflammation, and activated MAPK via the Toll-like receptor 4 (TLR4) to promote proliferation and migration, as well as up-regulate the expression of miR-632, which targeted GSK3β to activate Wnt/β-catenin to boost proliferation and migration in a positive feedback manner. Notably, OA-RD17 promoted transition from the inflammatory to proliferative stage, accelerated epidermal and granulation regeneration, and exhibited therapeutic effects on mouse and diabetic patient ex vivo skin wounds. MiR-632 activated Wnt/β-catenin to promote full-thickness skin wound healing in rats.

Conclusions
OA-RD17 exhibited promising therapeutic effects on mice (full-thickness, deep second-degree burns), and ex vivo skin wounds in diabetic patients by regulating macrophages proliferation, migration, and polarization (MAPK, NF-κB), and keratinocytes proliferation and migration (TLR4/MAPK/miR-632/Wnt/β-catenin molecular axis). Moreover, miR-632 also activated Wnt/β-catenin to promote full-thickness skin wound healing in rats. Notably, our results indicate that OA-RD17 and miR-632 are promising pro-healing drug candidates.

Graphical Abstract
A case report: anteroseptal ST elevation due to acute isolated right ventricular infarction
Authors: Sukmawati Indah , Goh Fang Qin , Yip Alfred , Loh Poay Huan , Chan Koo Hui 
Published: July 2023

Abstract
Background
Electrocardiogram (ECG) is the first diagnostic tool physicians use in diagnosing acute myocardial infarction (MI). In this case report, we present a case where the initial ECG diagnosis was that of an acute anteroseptal MI but emergency coronary angiography showed that the infarct-related artery was a small non-dominant right coronary artery (RCA) instead of the anticipated left anterior descending artery (LAD). Isolated right ventricular (RV) infarction from a non-dominant RCA is rarely seen in clinical practice, and it may exhibit ECG changes that can be confused with an acute anteroseptal MI. It is important to appreciate the subtle differences in the ECG changes that occur in either of these two types of MI for appropriate diagnosis and treatment.

Case presentation
A 49-year-old non-smoking male with prior coronary stent implantation in LAD presented with acute chest pain and his pre-hospital ECG indicated an anteroseptal STEMI possibly due to stent thrombosis, but an emergency angiogram showed patent LAD and Circumflex arteries. There was however thrombotic occlusion of the right, non-dominant coronary artery, which was revascularized with a drug-eluting stent. The patient’s chest pain and ST elevations resolved, and subsequent echo showed moderate RV systolic dysfunction in keeping with RV myocardial infarction.

Discussion
RV myocardial infarction is usually due to an occlusion of the dominant RCA proximal to the origin of its RV wall branch, which often results in inferior ST elevation with reciprocal anterior ST depression. The ST elevation over V1 which would accompany RV infarction is often masked due to the more dominant electrical forces of inferior and posterior LV wall infarction. Our case demonstrates that in isolated RV infarction due to non-dominant proximal RCA occlusion, anterior ST elevation can be seen over V1-3, being most prominent in V1, which overlies the right ventricle, and resolved after restoring flow to the RCA. Spatial vector analysis of the ECG or right-sided ECG leads would be helpful to aid the diagnosis of RV infarction when clinical suspicion is present, for example when there is significant hypotension, raised jugular venous pressure but clear lung fields or deterioration after nitrate administration.