bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Lianhuaqingwen Capsules in adults with mild-to-moderate coronavirus disease 2019: an international, multicenter, double-blind, randomized controlled trial
Authors: Zheng Jin-ping , Ling Yun , Jiang Liang-shuang , Mootsikapun Piroon , Lu Hong-zhou , Chayakulkeeree Methee , Zhang Li-xiu , Arttawejkul Pureepat , Hu Feng-yu , Truong Thi Ngoc Lan , Perez Roxan A. , Gu Xing , Sun Hui-min , Jiang Jian-jie , Liu Ren-jie , Ding Zhen , Zhan Yang-qing , Yang Zi-feng , Guan Wei-jie , Zhong Nan-shan 
Published: November 2023

Abstract
Background
In a randomized trial, Lianhuaqingwen (LHQW) capsule was effective for accelerating symptom recovery among patients with coronavirus disease 2019 (COVID-19). However, the lack of blinding and limited sample sizes decreased the level of clinical evidence.

Objectives
To evaluate the efficacy and safety of LHQW capsule in adults with mild-to-moderate COVID-19.

Methods
We conducted a double-blind randomized controlled trial in adults with mild-to-moderate COVID-19 (17 sites from China, Thailand, Philippine and Vietnam). Patients received standard-of-care alone or plus LHQW capsules (4 capsules, thrice daily) for 14 days. The primary endpoint was the median time to sustained clinical improvement or resolution of nine major symptoms.

Results
The full-analysis set consisted of 410 patients in LHQW capsules and 405 in placebo group. LHQW significantly shortened the primary endpoint in the full-analysis set (4.0 vs. 6.7 days, hazards ratio: 1.63, 95% confidence interval: 1.39-1.90). LHQW capsules shortened the median time to sustained clinical improvement or resolution of stuffy or runny nose (2.8 vs. 3.7 days), sore throat (2.0 vs. 2.6 days), cough (3.2 vs. 4.9 days), feeling hot or feverish (1.0 vs. 1.3 days), low energy or tiredness (1.3 vs. 1.9 days), and myalgia (1.5 vs. 2.0 days). The duration to sustained clinical improvement or resolution of shortness of breath, headache, and chills or shivering did not differ significantly between the two groups. Safety was comparable between the two groups. No serious adverse events were reported.

Interpretation
LHQW capsules promote recovery of mild-to-moderate COVID-19 via accelerating symptom resolution and were well tolerated.
Trial registrationChiCTR2200056727.
Targeting PEG10 as a novel therapeutic approach to overcome CDK4/6 inhibitor resistance in breast cancer
Authors: Katuwal Nar Bahadur , Kang Min Sil , Ghosh Mithun , Hong Sa Deok , Jeong Yeong Gyu , Park Seong Min , Kim Seul-Gi , Sohn Joohyuk , Kim Tae Hoen , Moon Yong Wha 
Published: November 2023

Abstract
Background
Breast cancer is the global leading cancer burden in women and the hormone receptor-positive (HR+) subtype is a major part of breast cancer. Though cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are highly effective therapy for HR+ subtype, acquired resistance is inevitable in most cases. Herein, we investigated the paternally expressed gene 10 (PEG10)-associated mechanism of acquired resistance to CDK4/6 inhibitors.

Methods
Palbociclib-resistant cells were generated by exposing human HR+ breast cancer cell lines to palbociclib for 7–9 months. In vitro mechanistic study and in vivo xenograft assay were performed. For clinical relevance, public mRNA microarray data sets of early breast cancer were analyzed and PEG10 immunohistochemical staining was performed using pre-CDK4/6 inhibitor tumor samples.

Results
We observed that PEG10 was significantly upregulated in palbociclib-resistant cells. Ectopic overexpression of PEG10 in parental cells caused CDK4/6 inhibitor resistance and enhanced epithelial–mesenchymal transition (EMT). On the contrary, PEG10-targeting siRNA or antisense oligonucleotides (ASOs) combined with palbociclib synergistically inhibited proliferation of palbociclib-resistant cells and growth of palbociclib-resistant xenograft in mice and suppressed EMT as well. The mechanistic study confirmed that high PEG10 expression suppressed p21, a natural CDK inhibitor, and SIAH1, a post-translational degrader of ZEB1, augmenting CDK4/6 inhibitor resistance. Then PEG10 siRNA combined with palbociclib suppressed cell cycle progression and EMT via activating p21 and SIAH1, respectively. Consequently, combined PEG10 inhibition and palbociclib overcame CDK4/6 inhibitor resistance. Furthermore, high PEG10 expression was significantly associated with a shorter recurrence-free survival (RFS) based on public mRNA expression data. In pre-CDK4/6 inhibitor treatment tissues, PEG10 positivity by IHC also showed a trend toward a shorter progression-free survival (PFS) with CDK4/6 inhibitor. These results support clinical relevance of PEG10 as a therapeutic target.

Conclusions
We demonstrated a novel PEG10-associated mechanism of CDK4/6 inhibitor resistance. We propose PEG10 as a promising therapeutic target for overcoming PEG10-associated resistance to CDK4/6 inhibitors.
Foot biomechanics in patients with advanced subtalar‐ and mid‐tarsal joint osteoarthritis and poorly responding to conservative treatment
Authors: Deschamps Kevin , Mercken Karel , Verschuren Pieter , Eerdekens Maarten , Vanstraelen Eline , Wuite Sander , Matricali Giovanni A. 
Published: November 2023

AbstractBackgroundA comprehensive insight into the effects of subtalar‐ and mid‐tarsal joint osteoarthritis on lower limb's biomechanical characteristics during walking is lacking. Our goal was to assess joint kinematics and kinetics and compensatory mechanisms in patients with subtalar and mid‐tarsal joint osteoarthritis.MethodsPatients with symptomatic and radiographically confirmed osteoarthritis of the subtalar and mid‐tarsal (n = 10) and an asymptomatic control group (n = 10) were compared. Foot joint kinematics and kinetics during the stance phase of walking were quantified using a four‐segment foot model.ResultsDuring pre‐swing phase, the tibio‐talar range of motion in the sagittal plane of the patient group decreased significantly (P = 0.001), whereas the tarso‐metatarsal joint range of motion in the sagittal plane was greater in the pre‐swing phase (P = 0.003). The mid‐tarsal joint showed lower transverse plane range of motion in the patient group during the loading response and pre‐swing phase (P < 0.001 resp. P = 0.002). The patient group showed a lower Tibio‐talar joint peak plantarflexion moment (P = 0.004), peak plantarflexion velocity (P < 0.001) and peak power generation in the sagittal plane (P < 0.001), and a lower mid‐tarsal joint peak adduction and abduction velocity (P < 0.001 resp. P < 0.001) and peak power absorption (P < 0.001).ConclusionsThese findings suggest that patients with subtalar and mid‐tarsal joint osteoarthritis adopt a cautious walking strategy potentially dictated by pain, muscle weakness, kinesiophobia and stiffness. Since this poorly responding population faces surgical intervention on the short term, we recommend careful follow‐up after fusion surgery since biomechanical outcome measures associated to this post‐surgical stage is lacking.
Eco-friendly monitoring of triclosan as an emerging antimicrobial environmental contaminant utilizing electrochemical sensors modified with CNTs nanocomposite transducer layer
Authors: Safwat Nardine , Mahmoud Amr M. , Abdel-Ghany Maha F. , Ayad Miriam F. 
Published: November 2023

AbstractEnvironmental appearance of antimicrobials due to frequent use of personal care products as recommended by WHO can cause serious flare-up of antimicrobial resistance. In this work, three eco-friendly microfabricated copper solid-state sensors were developed for measuring triclosan in water. Multi-walled carbon nanotubes were incorporated in sensor 2 and 3 as hydrophobic conductive inner layer. Meanwhile, β-cyclodextrin was incorporated in sensor 3 as an ionophore for selective binding of TCS in presence of interfering compounds. The obtained linear responses of sensors 1, 2 and 3 were (1 × 10− 8–1 × 10− 3 M), (1 × 10− 9–1 × 10− 3 M) and (1 × 10− 10– 1 × 10− 3 M), respectively. Limit of detection was 9.87 × 10− 9 M, 9.62 × 10− 10 M, and 9.94 × 10− 11 M, respectively. The miniaturized sensors were utilized for monitoring of triclosan in water samples.
Long-term follow-up of children with chronic non-bacterial osteomyelitis—assessment of disease activity, risk factors, and outcome
Authors: Reiser Christiane , Klotsche Jens , Hospach Toni , Heubner Georg , Windschall Daniel , Trauzeddel Ralf , Groesch Nadine , Niewerth Martina , Minden Kirsten , Girschick Hermann 
Published: November 2023

Abstract
Introduction
Chronic non-bacterial osteomyelitis (CNO) is an autoinflammatory bone-disease of unknown origin. The National Pediatric Rheumatologic Database (NPRD) collects long-term data of children and adolescents with rheumatic diseases including CNO.

Objective
To assess characteristics, courses, and outcomes of CNO with onset in childhood and adolescence and to identify outcome predictors.

Methods
From 2015 to 2021 patients with a confirmed diagnosis of CNO, who were registered in the NPRD during their first year of disease and at least one follow-up visit, were included in this analysis and observed for up to 4 years.

Results
Four hundred patients with recent diagnosis of CNO were enrolled in the NRPD during the study period. After 4 years, patient data documentation was sufficient to be analyzed in 81 patients. A significant decline of clinical and radiological lesions is reported: at inclusion in the registry, the mean number of clinical lesions was 2.0 and 3.0 MRI lesions per patient. A significant decrease of manifestations during 4 years of follow-up (mean clinical lesions 0.5, p < 0.001; mean MRI lesions 0.9 (p < 0.001)) was documented. A significant improvement of physician global disease activity (PGDA), patient-reported overall well-being, and childhood health assessment questionnaire (C-HAQ) was documented. Therapeutically, an increase of disease-modifying anti-rheumatic drugs over the years can be stated, while bisphosphonates rather seem to be considered as a therapeutic DMARD option in the first years of disease. Only 5–7% of the patients had a severe disease course as defined by a PGDA >  = 4. Predictors associated with a severe disease course include the site of inflammation (pelvis, lower extremity, clavicle), increased erythrocyte sedimentation rate, and multifocal disease at first documentation. The previously published composite PedCNO disease activity score was analyzed revealing a PedCNO70 in 55% of the patients at 4YFU.

Conclusion
An improvement of physician global disease activity (PGDA), patient reported overall well-being and imaging-defined disease activity measures was documented, suggesting that inactivity of CNO disease can be reached. PedCNO score and especially PGDA, MRI-defined lesions and in a number of patients also the C-HAQ seem to be reliable parameters for describing disease activity. The identification of risk factors at the beginning of the disease might influence treatment decision in the future.
Longitudinal changes in youth baseball batting based on body rotation and separation
Authors: Tsutsui Toshiharu , Sakata Jun , Sakamaki Wataru , Maemichi Toshihiro , Torii Suguru 
Published: November 2023

Abstract
Background
Identifying the characteristics of batting mechanics, such as the proper angle and position of each body segment in youth baseball players, is important for proper instructions. This study aimed to identify the age-related changes in batting kinematics including rotational and separational movements of the head, upper trunk, pelvis, and arms, in youth baseball players.

Methods
Over the three seasons, we measured the batting motion of baseball players aged 6- to 12 years using three high-speed cameras. Participants were divided into six age categories according to the little league eligibility rules (players were classified according to their age as of July 31 of a given year). Toss batting was performed using an automatic tossing machine set obliquely in front of the batter. Additionally, we analyzed the rotation angles of the head, upper trunk, pelvis, and arm direction, and the separation angles—calculated using the difference of each rotational angle and the head movement distance and step width—at five points in batting phase: stance, load, foot contact, pre-swing, and ball contact. Finally, 17 players from under 8 (U8, i.e., approximately 7–8 years) to U10 and 13 from U11 to U13 were analyzed. A one-way repeated measures analysis of variance was performed to analyze age-related changes in batting kinematics.

Results
Several age-related changes in batting kinematics at various batting point were observed. The head-to-upper trunk separation angle increased with age from U8 to U10 during the foot contact (effect sizes [ES] = 0.658) and from U11 to U13 during the pre-swing (ES = 0.630). Additionally, the U13 showed a significantly increase in the upper and pelvis separation angles during load, foot contact, and pre–swing compared with U11 and U12 (ES = 0.131, 0.793, and 0.480).

Conclusion
Various changes in batting kinematics occurred among each age group. Notably, U12 and U13 had the greater upper trunk-to-pelvis separation angle at foot contact and pre-swing compared to U11. Therefore, it would be important for the instruction of younger baseball players to understand the underdevelopment of trunk separation when batting and encourage the acquisition of such separation movements.
N6-methyladenosine-modified circRIMS2 mediates synaptic and memory impairments by activating GluN2B ubiquitination in Alzheimer's disease
Authors: Wang Xiong , Xie Jiazhao , Tan Lu , Lu Yanjun , Shen Na , Li Jiaoyuan , Hu Hui , Li Huijun , Li Xiaoguang , Cheng Liming 
Published: November 2023

Abstract
Background
Synaptic degeneration occurs in the early stage of Alzheimer's disease (AD) before devastating symptoms, strongly correlated with cognitive decline. Circular RNAs (circRNAs) are abundantly enriched in neural tissues, and aberrant expression of circRNAs precedes AD symptoms, significantly correlated with clinical dementia severity. However, the direct relationship between circRNA dysregulation and synaptic impairment in the early stage of AD remains poorly understood.

Methods
Hippocampal whole-transcriptome sequencing was performed to identify dysregulated circRNAs and miRNAs in 4-month-old wild-type and APP/PS1 mice. RNA antisense purification and mass spectrometry were utilized to unveil interactions between circRIMS2 and methyltransferase 3, N6-adenosine-methyltransferase complex catalytic subunit (METTL3). The roles of circRIMS2/miR-3968 in synaptic targeting of UBE2K-mediated ubiquitination of GluN2B subunit of NMDA receptor were evaluated via numerous lentiviruses followed by morphological staining, co-immunoprecipitation and behavioral testing. Further, a membrane-permeable peptide was used to block the ubiquitination of K1082 on GluN2B in AD mice.

Results
circRIMS2 was significantly upregulated in 4-month-old APP/PS1 mice, which was mediated by METTL3-dependent N6-methyladenosine (m6A) modification. Overexpression of circRIMS2 led to synaptic and memory impairments in 4-month-old C57BL/6 mice. MiR-3968/UBE2K was validated as the downstream of circRIMS2. Elevated UBE2K induced synaptic dysfunction of AD through ubiquitinating K1082 on GluN2B. Silencing METTL3 or blocking the ubiquitination of K1082 on GluN2B with a short membrane-permeable peptide remarkably rescued synaptic dysfunction in AD mice.

Conclusions
In conclusion, our study demonstrated that m6A-modified circRIMS2 mediates the synaptic and memory impairments in AD by activating the UBE2K-dependent ubiquitination and degradation of GluN2B via sponging miR-3968, providing novel therapeutic strategies for AD.
In silico prediction of bioequivalence of atorvastatin tablets based on GastroPlus™ software
Authors: Wang Lu , Chen Jinliang , Chen Wenjun , Ruan Zourong , Lou Honggang , Yang Dandan , Jiang Bo 
Published: November 2023

AbstractThe prediction of intestinal absorption of various drugs based on computer simulations has been a reality. However, in vivo pharmacokinetic simulations and virtual bioequivalence evaluation based on GastroPlus™ have not been found. This study aimed to simulate plasma concentrations with different dissolution profiles and run population simulations to evaluate the bioequivalence of test and reference products of atorvastation using GastroPlus software. The dissolution profiles of the reference and test products of atorvastatin (20 mg tablets), and clinical plasma concentration-time data of the reference product were used for the simulations. The results showed that the simulated models were successfully established for atorvastatin tablets. Population simulation results indicated that the test formulation was bioequivalent to the reference formulation. The findings suggest that modelling is an essential tool to demonstrating the possibility of pharmacokinetic and bioequivalence for atorvastatin. It will contribute to understanding the potential risks during the development of generic products.
Association of dietary behaviour and depression among adolescents in Malaysia: a cross-sectional study
Authors: Sahril Norhafizah , Adnan Muhammad Azri Adam , Khalil Muhamad Khairul Nazrin , Chan Yee Mang , Yoga Ratnam Kishwen Kanna , Lai Wai Kent , Ahmad Noor Ani 
Published: November 2023

Abstract
Background
Depression is on the rise and has become a significant concern for public health. Limited research has explored the connection between dietary patterns and depression. This investigation aimed to examine how dietary behaviours relate to depression among adolescents attending school in Malaysia.

Methods
The study utilized data from the National School-Based Health Survey 2022, a nationwide survey involving school-going adolescents aged 13–17, with a total of 33,523 participants from 239 schools. To assess depression, the study employed the Patient Health Questionnaire (PHQ-9), considering a score of 10 or higher as indicative of depression. Dietary behaviours were assessed using a validated self-administered questionnaire adapted from the World Health Organization's Global School-based Student Health Survey. Descriptive analysis and complex sample logistic regression were carried out using SPSS version 26.0.

Results
The study revealed a 26.9% overall prevalence of depression, with higher risks among female adolescents (AOR 2.71, 95% CI 2.51, 2.92) and those in higher grades. Malays (AOR 1.71, 95% CI 1.41, 2.07), Other Bumiputeras (AOR 1.69, 95% CI 1.32, 2.17), and Others (AOR 1.63, 95% CI 1.16, 2.30) had elevated odds of depression compared to Indians. Healthy dietary habits, like consuming less than two servings of fruits daily, correlated with depression (AOR 1.44 95% CI 1.35, 1.54). Additionally, unhealthy dietary behaviours such as fast food consumption (AOR 1.73 [95% CI 1.55, 1.93]) and carbonated soft drink intake (AOR 1.59 [95% CI 1.48, 1.70]) were positively associated with depression.

Conclusions
One out of every four Malaysian adolescents was identified to experience depression. Depression was linked to several factors, such as being female, belonging to higher grade levels, identifying as Malays, Other Bumiputeras, or belonging to other ethnicities, and participating in the consumption of fast food, carbonated soft drinks, and fruits. To address these observations, it is crucial to formulate effective public health programmes that prioritize adolescent mental health and encourage the adoption of healthy eating habits.
The Prose of Our Land: Ban Kōkei, Translation, and National Language Consciousness in Eighteenth-Century Japan
Authors: Clements Rebekah 
Published: November 2023

Abstract
Today, Ban Kōkei 伴蒿蹊 (1733–1806) is mostly known as the author of a collection of biographies, which became one of the best-selling books of Japan's late eighteenth century. However, he also devoted much of his career to developing the expressive potential of Japanese prose writing. This article locates Kōkei's promotion of language reform within the context of contemporaneous developments in translation from classical into vernacular Japanese and explains the role of translation in Kōkei's attempts to develop Japanese prose writing nearly one hundred years before the better-known national language advocacy of the “Unification of the Spoken and Written Languages” (Genbun itchi 言文一致) movement of the Meiji period (1868–1912). Considered alongside canonical figures like Motoori Norinaga and Ogyū Sorai, Kōkei's lesser-known work is evidence of a nascent “national” language consciousness among Japanese intellectuals prior to the Meiji period.
Liver metastases from colorectal carcinoma: performance of pathological response scores
Authors: ben slama Sana , Mallek Ines , Ben Othman Nadia , Bouchabou Bochra , Nakhli Abdelwahab , Hajri Mohammed , Mestiri Hafedh , Lahmar Ahlem , Bacha Dhouha 
Published: November 2023

Background: Pathological response of liver metastases (LM) from colorectal carcinoma (CRC) to neoadjuvant therapy is one of the prognostic factors correlated with recurrence and survival. The aim of this study was to compare the performance of two prognostic scores in patients operated for colorectal cancer liver metastases (CRCLM). Methods: A study was performed of patients who underwent preoperative chemotherapy (CT), followed by resection of LM, from 2015-2021. Pathological response was evaluated according to Rubbia-Brandt tumor regression grade (TRG) and the Blazer scoring system. Then, we studied the performance of these two prognostic scores, based on homogeneity using the likelihood Ratio (LR+), monotonicity and discriminative ability using the area under the receiver operating characteristic (ROC) curve (AUC). Results: 70 cases were included in the study. Mean age was 56 years. The sex ratio was 2.2. Forty patients were stage IV (57%) with synchronous all CRCLMs. The overall survival, all stages combined, was 85.5% at 12 months, 41.7% at 24 months and 19.3% at 36 months. The mean survival was better in case of major response (TRG1/TRG2) evaluated at 40.1 and 41.1 months after diagnosis. In cases of partial response (TRG3), the mean survival was 32.1 months. In cases with no response (TRG4/TRG5), survival was estimated at 29.9 and 18.5 months. The Rubbia-Brandt TRG had the highest LR+ (10.95). The LR+ of the Rubbia-Brandt score was greater than 10, so it was a test with very strong contribution. The LR+ of the Blazer score was between 5 and 10, it was a test with strong contribution. The Rubbia-Brandt TRG had the highest linearity value (10.73). With a higher AUC of the ROC curve (0.8), the Rubbia-Brandt TRG was better at predicting survival than the Blazer score.
Factors affecting consumers’ perception and willingness to pay for Fairtrade bananas during a cost-of-living crisis
Authors: Jahae Timo , Tremma Ourania , Aguiar Luís Kluwe 
Published: November 2023

The study set out to investigate factors affecting consumers’ ethical perception and willingness to pay for Fairtrade bananas during the cost-of-living crisis in the UK. A survey was distributed via social media resulting in 357 valid responses which were analyzed using IBM-SPSS-28. The main influencing factors on consumers’ perception of Fairtrade are still strong ethical beliefs towards socio-economic benefits to farmers followed by cost, convenience and quality. No demographic factors significantly influenced purchase behaviour. A framework representing the factors influencing consumers was proposed.
During a cost-of-living crisis, despite some consumers’ price sensitivity, they are still willing to purchase and pay more for Fairtrade bananas. Ethical knowledge and personal values sustain the purchase of ethically produced bananas. However, consumption would remain strong provided the price premium paid is not substantially high. When targeting consumers, the focus on overall awareness of Fairtrade and its values should be the key features in promotion campaigns.