bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design of the STRIVE-IPF trial- study of therapeutic plasma exchange, rituximab, and intravenous immunoglobulin for acute exacerbations of idiopathic pulmonary fibrosis
Authors: Kulkarni Tejaswini , Criner Gerard J. , Kass Daniel J. , Rosas Ivan O. , Scholand Mary Beth , Dilling Daniel F. , Summer Ross , Duncan Steven R. 
Published: March 2024

Abstract
Background
Acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) affect a significant proportion of patients with IPF. There are limited data to inform therapeutic strategies for AE-IPF, despite its high mortality. We discuss the rationale and design of STRIVE-IPF, a randomized, multi-center, open-label Phase IIb clinical trial to determine the efficacy of combined therapeutic plasma exchange (TPE), rituximab, and intravenous immunoglobulin (IVIG), in comparison to treatment as usual (TAU), among patients with acute IPF exacerbations.

Methods
The STRIVE-IPF trial will randomize 51 patients among five sites in the United States. The inclusion criteria have been designed to select a study population with AE-IPF, as defined by American Thoracic Society criteria, while excluding patients with an alternative cause for a respiratory decompensation. The primary endpoint of this trial is six-month survival. Secondary endpoints include supplement oxygen requirement and six-minute walk distance which will be assessed immediately prior to treatment and after completion of therapy on day 19, as well as at periodic subsequent visits.

Discussion
The experimental AE-IPF therapy proposed in this clinical trial was adapted from treatment regimens used in other antibody-mediated diseases. The regimen is initiated with TPE, which is expected to rapidly reduce circulating autoantibodies, followed by rituximab to reduce B-cells and finally IVIG, which likely has multiple effects, including affecting feedback inhibition of residual B-cells by Fc receptor occupancy. We have reported potential benefits of this experimental therapy for AE-IPF in previous anecdotal reports. This clinical trial has the potential to profoundly affect current paradigms and treatment approaches to patients with AE-IPF.

Trial registration
ClinicalTrials.gov identifier: NCT03286556.
Artesunate-loaded thermosensitive chitosan hydrogel promotes osteogenesis of maxillary tooth extraction through regulating T lymphocytes in type 2 diabetic rats
Authors: Luo Jinghong , Liang Chen , Chen Kun , Zeng Kai , Bai Rui , Tang Chan , Li Jiaquan , Nong Xiaolin 
Published: March 2024

Abstract
Background
Type 2 diabetes mellitus (T2DM) causes severe bone loss after tooth extraction as a hyperglycemic environment causes aberrant bone homeostasis. Artesunate (ART) is known to possess anti-inflammation and osteogenic properties. However, its osteogenesis property in alveolar bone remains unclear. This study aimed to explore the osteogenic and immunoregulatory effects of artesunate-loaded thermosensitive chitosan hydrogel (ART-loaded TCH) on maxilla tooth extraction in T2DM rats.

Methods
T2DM rats were induced by a high-fat diet and streptozotocin. Different concentrations of ART-loaded TCH were applied in tooth extraction sockets. Bone loss and the expression of osteogenic regulatory factors (OPG, ALP, RANK) were evaluated. The immunoregulatory effects of ART-loaded TCH were observed through detecting the infiltration of T lymphocytes and their cytokines. The underlying mechanisms were explored.

Results
Results showed that the 150 mg/ml ART-loaded TCH group significantly ameliorated maxilla bone height and bone mineral density when compared with the T2DM group (p < 0.05). It also improved the expression of OPG, ALP, and RANK. Although the alteration of CD4+ T, CD8+ T, and CD4+:CD8+ T ratio has no significant difference among groups, the release of Th1 and Th2 in the 150 mg/ml ART-loaded TCH group has been significantly regulated than in the T2DM group (p < 0.05). Besides, ART-loaded TCH treatment inhibited the expression of p38 MAPK and ERK1 in T2DM maxilla.

Conclusions
Therefore, the results indicated that 150 mg/ml ART-loaded TCH could be an effective method to prevent bone loss in T2DM tooth extraction rats by modulating the immunoregulation of Th1 and Th2 and the MAPK signaling pathway.
Evaluation of enamel surface integrity after orthodontic bracket debonding: comparison of three different system
Authors: Ghaleb Labib , Al-Worafi Naseem Ali , Thawaba Ahmed , Abdulqader Abbas Ahmed , Alkamel Aqlan , Abdo Yaser , Yang Zhao , Noman Nashwan , Al-Aroomi Maged Ali , Yulou Tian 
Published: March 2024

Abstract
Objective
This study aimed to evaluate enamel surface integrity and time consumed during residual cement removal after bracket debonding using different adhesive removal burs with and without a dental loupe.

Material and Methods
Sixty human-extracted premolars were collected, cleaned, mounted, and prepared for orthodontic bracket bonding. Teeth were randomly divided into three main groups (n = 20) based on the adhesive removal method: tungsten carbide system (TC), sof-lex discs system (SD), and diamond system (DB) groups. Then, each group was subdivided into two subgroups (naked eye and magnifying loupe subgroups). The brackets were bonded and then debonded after 24 h, and the Adhesive Remnant Index (ARI) was assessed. The adhesive remnants were removed by different systems, and the final polishing was performed by Silicone OneGloss. The enamel surface roughness was evaluated before bracketing (T0), after residual cement removal (T1), and finally after polishing (T2) using surface Mitutoyo SJ-210 profilometry and Scanning Electron Microscopy (SEM) to determine the Enamel Damage Index (EDI) score. The time consumed for adhesive removal was recorded in seconds.

Results
The Kruskal Wallis test showed a statistically significant difference in roughness values at T1 compared to T2 between subgroups (p < 0.001). When comparing EDI at T1 and T2, the Kruskal–Wallis H-test showed statistically significant differences in all subgroups. The pairwise comparisons revealed that EDI scores showed a statistically significant difference at T1 and T2 between DB vs. TC and SD (p = 0.015) but not between TC vs. SD (p = 1.000), indicating the highest roughness value observed in the DB group. The time for cement removal was significantly shorter in the magnifying loupe group than in the naked eye group and was shortest with the TC group, whereas the time was the longest with the DB group (p < 0.05).

Conclusion
All three systems were clinically satisfactory for residual orthodontic adhesive removal. However, TC system produced the lowest enamel roughness, while the DB system created the greatest. The polishing step created smoother surfaces regardless of the systems used for resin removal.
Analysis of cybersickness in virtual nursing simulation: a German longitudinal study
Authors: Biniok Maria , Forbrig Theresa A. , Gellert Paul , Gräske Johannes 
Published: March 2024

Abstract
Background
Innovative educational approaches such as simulation-based nursing education using virtual reality (VR) technologies provide new opportunities for nursing education. However, there is a lack of information on side effects, especially health-related side effects, of head-mounted displays (HMDs) on the human body when using VR devices for nursing simulation. This study aims to validate the German version of the Virtual Reality Sickness Questionnaire (VRSQ) and to evaluate its associations with sex and age, as reflected in the VRSQG scores (total score, oculomotor, and disorientation) over time.

Methods
A longitudinal-sectional study was conducted. In addition to the VRSQG (pre-, post-, and 20 min post-intervention), participants (all nursing students) completed data on personal characteristics. Participants completed a VR simulation of a blood draw. Confirmatory factor analysis (CFA) was used to evaluate whether the measured construct was consistent with the original. In addition to the validity, internal consistency was analyzed and generalized linear models (GLMs) were used for data analysis.

Results
A total of 38 nursing students (mean age 26.8 years; SD = 7.1, 79.0% female) participated. The mean time spent in the VR simulation was 21 min. All participants completed the entire simulation. The CFA indicates (CFI = 0.981, SRMR = 0.040) VRSQG structure is given. Internal consistency showed low values for the subdomain Oculomotor (Cronbach alpha 0.670). For Disorientation and the Total score values showed a sufficient internal consistency. GLMs showed significant between subject associations with age over time with VRSQG total score, oculomotor, and disorientation. Older nursing students start with higher VRSQG-Scores. Over time, an approximation occurs, so that all participants reach a similar level by the final measurement point. No associations were found between sex (male/female) and VRSQG scores.

Conclusions
The VRSQG is a reliable and valid self-assessment for measuring cybersickness in VR based nursing simulations, with cybersickness symptoms positively associated with age. However, in depth-evaluation regarding age-associations with cybersickness should be done. As well as studies to explore additional associations and emphasizes the importance of establishing cut-off values to assess the clinical relevance of the scores.
Inverse association between plasma chlordecone concentrations and progression of alcoholic liver fibrosis: the role of liver metabolism
Authors: Gelu-Simeon Moana , Lafrance Marie-Josée , Michineau Leah , Saillard Eric , Thomé Jean Pierre , Emond Claude , Samson Michel , Multigner Luc 
Published: March 2024

Abstract
Background and Aims
Chlordecone is a persistent organochlorinated insecticide, extensively used in the French West Indies and has been contaminating the population for more than thirty years. Its potentiation effect on hepatotoxic agents has been demonstrated in animal models. We investigated the relationship between environmental exposure to chlordecone and the progression of liver fibrosis.

Methods
This study included 182 consecutive patients with chronic alcoholic hepatitis whose liver fibrosis was assessed using non-invasive methods. Measured plasma chlordecone concentrations at inclusion were used as surrogate of long-term exposure under steady-state conditions. As the pharmacokinetic processing of chlordecone is largely determined by the liver, we used a human physiologically based pharmacokinetic model to predict plausible changes in the steady-state blood chlordecone concentrations induced by liver fibrosis.

Results
With a median follow-up of 27.1 years after the onset of alcohol consumption, we found a significant decrease in the risk of advanced liver fibrosis with increasing plasma chlordecone concentration (adjusted hazard ratio = 0.56; 95% confidence interval: 0.34–0.95 for the highest vs. lowest tertile, p = 0.04). Changes induced by liver fibrosis influenced the pharmacokinetic processing of chlordecone, resulting in substantial modifications in its steady-state blood concentrations.

Conclusion
According to this human model of coexposure to alcohol, reverse causality is the most plausible explanation of this inverse association between plasma chlordecone concentrations and progression of liver fibrosis. This study underlines the importance of considering the pharmacokinetic of environmental contaminants in epidemiological studies when biomarkers of exposure are used to investigate their own impact on the liver.

Trial registration
ClinicalTrials.gov Identifier: NCT03373396.
PDGFRβ + cell HIF2α is dispensable for white adipose tissue metabolic remodeling and hepatic lipid accumulation in obese mice
Authors: Yao Tao , Wei Danni , Tian Xin , Zhao Lin , Wan Qiangyou , Zhang Xiaoli , Cai Juan , Li Siqi , Diao Bowen , Feng Suihan , Shan Bo , Shao Mengle , Wu Ying 
Published: March 2024

Abstract
Background
Obesity is associated with extensive white adipose tissue (WAT) expansion and remodeling. Healthy WAT expansion contributes to the maintenance of energy balance in the liver, thereby ameliorating obesity-related hepatic steatosis. Tissue-resident mesenchymal stromal cell populations, including PDGFRβ + perivascular cells, are increasingly recognized pivotal as determinants of the manner in which WAT expands. However, the full array of regulatory factors controlling WAT stromal cell functions remains to be fully elucidated. Hypoxia-inducible factors (HIFs) are critical regulators in WAT stromal cell populations such as adipocyte precursor cells (APCs). It is revealed that HIF1α activation within PDGFRβ + stromal cells results in the suppression of de novo adipogenesis and the promotion of a pro-fibrogenic cellular program in obese animals. However, the role of HIF2α in PDGFRβ + cells remains undetermined in vivo.

Methods
New genetic models were employed in which HIF1α (encoded by the Hif1a gene) and HIF2α (encoded by the Epas1 gene) are selectively inactivated in PDGFRβ + cells in an inducible manner using tamoxifen (TAM). With these models, both in vitro and in vivo functional analysis of PDGFRβ + cells lacking HIF proteins were performed. Additionally, comprehensive metabolic phenotyping in diet-induced mouse models were performed to investigate the roles of PDGFRβ + cell HIF proteins in WAT remodeling, liver energy balance and systemic metabolism.

Results
Unlike HIF1α inactivation, the new findings in this study suggest that inducible ablation of HIF2α in PDGFRβ + cells does not cause apparent effects on WAT expansion induced by obesogenic diet. The adipogenic ability of PDGFRβ + APCs is not significantly altered by genetic HIF2α ablation. Moreover, no difference of key parameters associated with healthy WAT remodeling such as improvements of WAT insulin sensitivity, reduction in metabolic inflammation, as well as changes in liver fat accumulation or systemic glucose metabolism, is detected in PDGFRβ + cell Epas1-deficient mice.

Conclusion
The new findings in this study support that, in contrast to HIF1α, PDGFRβ + cell HIF2α appears dispensable for WAT metabolic remodeling and the resulting effects on liver metabolic homeostasis in diet-induced obesity, underscoring the isoform-specific roles of HIFα proteins in the regulation of adipose tissue biology.
Asiatic acid cyclodextrin inclusion micro-cocrystal for insoluble drug delivery and acute lung injury therapy enhancement
Authors: Shen Huan , Pan Li , Ning Keke , Fang Yuefei , Muhitdinov Bahtiyor , Liu Ergang , Huang Yongzhuo 
Published: March 2024

Abstract
Background
Acute lung injury (ALI) is a fatal respiratory disease caused by overreactive immune reactions (e.g., SARS-CoV-2 infection), with a high mortality rate. Its treatment is often compromised by inefficient drug delivery barriers and insufficient potency of the currently used drugs. Therefore, developing a highly effective lung-targeted drug delivery strategy is a pressing clinical need.

Results
In this study, the micro-sized inclusion cocrystal of asiatic acid/γ-cyclodextrin (AA/γCD, with a stoichiometry molar ratio of 2:3 and a mean size of 1.8 μm) was prepared for ALI treatment. The dissolution behavior of the AA/γCD inclusion cocrystals followed a “spring-and-hover” model, which meaned that AA/γCD could dissolve from the cocrystal in an inclusion complex form, thereby promoting a significantly improved water solubility (nine times higher than free AA). This made the cyclodextrin-based inclusion cocrystals an effective solid form for enhanced drug absorption and delivery efficiency. The biodistribution experiments demonstrated AA/γCD accumulated predominantly in the lung (Cmax = 50 µg/g) after systemic administration due to the micron size-mediated passive targeting effect. The AA/γCD group showed an enhanced anti-inflammatory therapeutic effect, as evidenced by reduced levels of pro-inflammatory cytokines in the lung and bronchoalveolar lavage fluids (BALF). Histological examination confirmed that AA/γCD effectively inhibited inflammation reactions.

Conclusion
The micro-sized inclusion cocrystals AA/γCD were successfully delivered into the lungs by pulmonary administration and had a significant therapeutic effect on ALI.

Graphic abstract
Long-term outcomes of robot-assisted versus minimally invasive esophagectomy in patients with thoracic esophageal cancer: a propensity score-matched study
Authors: Sakurai Toru , Hoshino Akihiro , Miyoshi Kenta , Yamada Erika , Enomoto Masaya , Mazaki Junichi , Kuwabara Hiroshi , Iwasaki Kenichi , Ota Yoshihiro , Tachibana Shingo , Hayashi Yutaka , Ishizaki Tetsuo , Nagakawa Yuichi 
Published: March 2024

Abstract

Background
Recently, robot-assisted minimally invasive esophagectomy (RAMIE) has gained popularity worldwide. Some studies have compared the long-term results of RAMIE and minimally invasive esophagectomy (MIE). However, there are no reports on the long-term outcomes of RAMIE in Japan. This study compared the long-term outcomes of RAMIE and MIE.

Methods
This retrospective study included 86 patients with thoracic esophageal cancer who underwent RAMIE or MIE at our hospital from June 2010 to December 2016. Propensity score matching (PSM) was employed, incorporating co-variables such as confounders or risk factors derived from the literature and clinical practice. These variables included age, sex, body mass index, alcohol consumption, smoking history, American Society of Anesthesiologists stage, comorbidities, tumor location, histology, clinical TNM stage, and preoperative therapy. The primary endpoint was 5-year overall survival (OS), and the secondary endpoints were 5-year disease-free survival (DFS) and recurrence rates.

Results
Before PSM, the RAMIE group had a longer operation time (min) than the MIE group (P = 0.019). RAMIE also exhibited significantly lower blood loss volume (mL) (P < 0.001) and fewer three-field lymph node dissections (P = 0.028). Postoperative complications (Clavien–Dindo: CD ≥ 2) were significantly lower in the RAMIE group (P = 0.04), and postoperative hospital stay was significantly shorter than the MIE group (P < 0.001). After PSM, the RAMIE and MIE groups consisted of 26 patients each. Blood loss volume was significantly smaller (P = 0.012), postoperative complications (Clavien–Dindo ≥ 2) were significantly lower (P = 0.021), and postoperative hospital stay was significantly shorter (P < 0.001) in the RAMIE group than those in the MIE group. The median observation period was 63 months. The 5-year OS rates were 73.1% and 80.8% in the RAMIE and MIE groups, respectively (P = 0.360); the 5-year DFS rates were 76.9% and 76.9% in the RAMIE and MIE groups, respectively (P = 0.749). Six of 26 patients (23.1%) in each group experienced recurrence, with a median recurrence period of 41.5 months in the RAMIE group and 22.5 months in the MIE group.

Conclusions
Compared with MIE, RAMIE led to no differences in long-term results, suggesting that RAMIE is a comparable technique.
Development and validation of predictive models for myopia onset and progression using extensive 15-year refractive data in children and adolescents
Authors: Zhao Jing , Yu Yanze , Li Yiming , Li Feng , Zhang Zhe , Jian Weijun , Chen Zhi , Shen Yang , Wang Xiaoying , Ye Zhengqiang , Huang Chencui , Zhou Xingtao 
Published: March 2024

Abstract
Background
Global myopia prevalence poses a substantial public health burden with vision-threatening complications, necessitating effective prevention and control strategies. Precise prediction of spherical equivalent (SE), myopia, and high myopia onset is vital for proactive clinical interventions.

Methods
We reviewed electronic medical records of pediatric and adolescent patients who underwent cycloplegic refraction measurements at the Eye & Ear, Nose, and Throat Hospital of Fudan University between January 2005 and December 2019. Patients aged 3–18 years who met the inclusion criteria were enrolled in this study. To predict the SE and onset of myopia and high myopia in a specific year, two distinct models, random forest (RF) and the gradient boosted tree algorithm (XGBoost), were trained and validated based on variables such as age at baseline, and SE at various intervals. Outputs included SE, the onset of myopia, and high myopia up to 15 years post-initial examination. Age-stratified analyses and feature importance assessments were conducted to augment the clinical significance of the models.

Results
The study enrolled 88,250 individuals with 408,255 refraction records. The XGBoost-based SE prediction model consistently demonstrated robust and better performance than RF over 15 years, maintaining an R2 exceeding 0.729, and a Mean Absolute Error ranging from 0.078 to 1.802 in the test set. Myopia onset prediction exhibited strong area under the curve (AUC) values between 0.845 and 0.953 over 15 years, and high myopia onset prediction showed robust AUC values (0.807–0.997 over 13 years, with the 14th year at 0.765), emphasizing the models' effectiveness across age groups and temporal dimensions on the test set. Additionally, our classification models exhibited excellent calibration, as evidenced by consistently low brier score values, all falling below 0.25. Moreover, our findings underscore the importance of commencing regular examinations at an early age to predict high myopia.

Conclusions
The XGBoost predictive models exhibited high accuracy in predicting SE, onset of myopia, and high myopia among children and adolescents aged 3–18 years. Our findings emphasize the importance of early and regular examinations at a young age for predicting high myopia, thereby providing valuable insights for clinical practice.
The implications of the Sudan war on healthcare workers and facilities: a health system tragedy
Authors: Badri Rawa , Dawood Iyas 
Published: March 2024

AbstractIn light of a collapsing healthcare system in Sudan, attacks on healthcare institutions and staff have markedly increased since the eruption of war on the 15th of April, costing many precious lives and valuable hospitals. Around 60 attacks on health facilities have been reported so far, many occupied by one or the other sides of the conflict, and the rest exhibit medication shortages and safety issues; hence, two-thirds of the medical centers are nonfunctioning. More than 200 violations against medical staff were recorded all over the country, which led to the death of 38 healthcare workers. Killing, kidnapping, and assaulting doctors, consequently led to a huge shortage in staff in the few barely working facilities, as the remaining health workers were concerned regarding their safety. Recommendations consisted of ceasing fire, restoring and resuming healthcare services, and insurance of a safe working environment. International collaboration and sufficient financial support are crucial to restore the healthcare system in Sudan.