bluuebunny/crossref_metadata_2025_split huggingface dataset:
Traditional Chinese medicine based on Tongjiang methodology combined with proton pump inhibitor (PPI) step-down in treating non-erosive reflux disease: a study protocol for a multicentered, randomized controlled clinical trial
Authors: Li Xia , Wu Haomeng , Zhang Beihua , Chen Ting , Shi Xiaoshuang , Ma Jinxin , Zhang Jiaqi , Tang Xudong , Wang Fengyun 
Published: October 2022

Abstract
Background
Non-erosive reflux disease (NERD) is characterized by typical gastroesophageal reflux symptoms, such as heartburn and regurgitation but an absence of esophageal mucosal damage during upper gastrointestinal endoscopy. Although proton pump inhibitors (PPIs) are the first line therapy, almost 50% of patients with NERD fail to respond to this treatment. Traditional Chinese medicine (TCM) can better relieve the symptoms of NERD. Therefore, a randomized controlled trial (RCT) was designed to investigate the efficiency of TCM granules based on Tongjiang (TJ) methodology combined with PPI step-down therapy for NERD patients who did not respond to PPIs alone.

Method
This multicentered, double-blinded, RCT with two parallel groups will recruit 174 participants who will be randomized into the TCM granules combined with PPI step-down group (n = 87) and the TCM granules placebo combined with PPI step-down group (n = 87). Both groups of participants will receive 6 weeks of treatment and 4 weeks of follow-up, and all participants will be assessed for related symptoms, mental health status, and quality of life at each visit. The primary outcome measurements include visual analog scale (VAS) for heartburn and regurgitation and the major symptoms scale. The secondary outcome measurements include PPI withdrawal rate, symptom recurrence rate, minor symptoms scale, SF-36, PRO, SAS, SDS, GERD–HRQL, and TCM syndromes scales.

Discussion
Previous research has shown that TCM is capable to alleviate NERD symptoms. This trial will help to provide a better understanding of the synergistic efficiency of the combination of TCM and PPIs, to explore whether the dosage of PPIs can be reduced after the supplement of TCM granules and to provide a feasible plan to reduce dependencies or withdraw NERD patients from PPIs. The outcome of this trial is expected to reduce the symptom recurrence rates, lessen patients’ physical and psychological burdens, and achieve good social benefits.

Trial registration
Clinicaltrials.gov NCT04340297. Registered on April 9, 2020
FORWARDS-1: an adaptive, single-blind, placebo-controlled ascending dose study of acute baclofen on safety parameters in opioid dependence during methadone-maintenance treatment—a pharmacokinetic-pharmacodynamic study
Authors: Paterson L. M. , Barker D. , Cro S. , Mozgunov P. , Phillips R. , Smith C. , Nahar L. , Paterson S. , Lingford-Hughes A. R. 
Published: October 2022

Abstract
Background
Treatment of opiate addiction with opiate substitution treatment (e.g. methadone) is beneficial. However, some individuals desire or would benefit from abstinence but there are limited options to attenuate problems with opiate withdrawal. Preclinical and preliminary clinical evidence suggests that the GABA-B agonist, baclofen, has the desired properties to facilitate opiate detoxification and prevent relapse. This study aims to understand whether there are any safety issues in administering baclofen to opioid-dependent individuals receiving methadone.

Methods
Opiate-dependent individuals (DSM-5 severe opioid use disorder) maintained on methadone will be recruited from addiction services in northwest London (NHS and third sector providers). Participants will be medically healthy with no severe chronic obstructive pulmonary disease or type 2 respiratory failure, no current dependence on other substances (excluding nicotine), no current severe DSM-5 psychiatric disorders, and no contraindications for baclofen or 4800 IU vitamin D (placebo). Eligible participants will be randomised in a 3:1 ratio to receive baclofen or placebo in an adaptive, single-blind, ascending dose design. A Bayesian dose-escalation model will inform the baclofen dose (10, 30, 60, or 90 mg) based on the incidence of ‘dose-limiting toxicity’ (DLT) events and participant-specific methadone dose. A range of respiratory, cardiovascular, and sedative measures including the National Early Warning Score (NEWS2) and Glasgow Coma Scale will determine DLT. On the experimental day, participants will consume their usual daily dose of methadone followed by an acute dose of baclofen or placebo (vitamin D3) ~ 1 h later. Measures including oxygen saturation, transcutaneous CO2, respiratory rate, QTc interval, subjective effects (sedation, drug liking, craving), plasma levels (baclofen, methadone), and adverse events will be obtained using validated questionnaires and examinations periodically for 5 h after dosing.

Discussion
Study outcomes will determine what dose of baclofen is safe to prescribe to those receiving methadone, to inform a subsequent proof-of-concept trial of the efficacy baclofen to facilitate opiate detoxification. To proceed, the minimum acceptable dose is 30 mg of baclofen in patients receiving ≤ 60 mg/day methadone based on the clinical experience of baclofen’s use in alcoholism and guidelines for the management of opiate dependence.

Trial registration
Clinicaltrials.gov NCT05161351. Registered on 16 December 2021.
Experiences of the Data Monitoring Committee for the RECOVERY trial, a large-scale adaptive platform randomised trial of treatments for patients hospitalised with COVID-19
Authors: Sandercock Peter A. G. , Darbyshire Janet , DeMets David , Fowler Robert , Lalloo David G. , Munavvar Mohammed , Staplin Natalie , Warris Adilia , Wittes Janet , Emberson Jonathan R. 
Published: October 2022

Abstract
Aim
To inform the oversight of future clinical trials during a pandemic, we summarise the experiences of the Data Monitoring Committee (DMC) for the Randomised Evaluation of COVID therapy trial (RECOVERY), a large-scale randomised adaptive platform clinical trial of treatments for hospitalised patients with COVID-19.

Methods and findings
During the first 24 months of the trial (March 2020 to February 2022), the DMC oversaw accumulating data for 14 treatments in adults (plus 10 in children) involving > 45,000 randomised patients. Five trial aspects key for the DMC in performing its role were: a large committee of members, including some with extensive DMC experience and others who had broad clinical expertise; clear strategic planning, communication, and responsiveness by the trial principal investigators; data collection and analysis systems able to cope with phases of very rapid recruitment and link to electronic health records; an ability to work constructively with regulators (and other DMCs) to address emerging concerns without the need to release unblinded mortality results; and the use of videoconferencing systems that enabled national and international members to meet at short notice and from home during the pandemic when physical meetings were impossible. Challenges included that the first four treatments introduced were effectively ‘competing’ for patients (increasing pressure to make rapid decisions on each one); balancing the global health imperative to report on findings with the need to maintain confidentiality until the results were sufficiently certain to appropriately inform treatment decisions; and reliably assessing safety, especially for newer agents introduced after the initial wave and in the small numbers of pregnant women and children included. We present a series of case vignettes to illustrate some of the issues and the DMC decision-making related to hydroxychloroquine, dexamethasone, casirivimab + imdevimab, and tocilizumab.

Conclusions
RECOVERY’s streamlined adaptive platform design, linked to hospital-level and population-level health data, enabled the rapid and reliable assessment of multiple treatments for hospitalised patients with COVID-19. The later introduction of factorial assessments increased the trial’s efficiency, without compromising the DMC’s ability to assess safety and efficacy. Requests for the release of unblinded primary outcome data to regulators at points when data were not mature required significant efforts in communication with the regulators by the DMC to avoid inappropriate early trial termination.
Males of Aedes aegypti show different clock gene expression profiles in the presence of conspecific females
Authors: Bezerra Jéssica Rodrigues Assunção , Bruno Rafaela Vieira , Araripe Luciana Ordunha 
Published: October 2022

AbstractBackgroundThe study of behavioral and physiological traits in mosquitoes has been mainly focused on females since males are not hematophagous and thus do not transfer the parasites that cause diseases in human populations. However, the performance of male mosquitoes is key for the expansion of populations and the perpetuation of mosquito species. Pre-copulatory communication between males and females is the initial and essential step for the success of copulation and studying the male facet of this interaction provides fertile ground for the improvement of vector control strategies. Like in most animals, reproduction, feeding, and oviposition are closely associated with locomotor activity in mosquitoes. Rhythmic cycles of locomotor activity have been previously described inAedes aegypti, and in females, they are known to be altered by blood-feeding and arbovirus infection. In previous work, we found that males in the presence of females significantly change their locomotor activity profiles, with a shift in the phase of the activity peak. Here, we investigated whether this shift is associated with changes in the expression level of three central circadian clock genes.MethodsReal-time PCR reactions were performed for the geneperiod,cycle, andcryptochrome 2in samples of heads, antennae, and abdominal tips of solitary males and males in the presence of females. Assays with antennae-ablated males were also performed, asking whether this is an essential organ mediating the communication and the variation in activity profiles.ResultsThe geneperiodshowed a conserved expression pattern in all tissues and conditions, while the other two genes varied according to the male condition. A remarking pattern was observed incry2, where the difference between the amplitude of expression at the beginning of photophase and the expression peak in the scotophase was greater when males were in the presence of females. Antennae ablation in males did not have a significant effect on the expression profiles, suggesting that female recognition may involve other senses besides hearing and olfaction.ConclusionOur results suggest that the expression of genecryptochrome 2varies in association with the interaction between males and females.Graphical abstract
Long-term maintenance of human endometrial epithelial stem cells and their therapeutic effects on intrauterine adhesion
Authors: He Wen , Zhu Xuejing , Xin Aijie , Zhang Hongdan , Sun Yiming , Xu Hua , Li He , Yang Tianying , Zhou Dan , Yan Hexin , Sun Xiaoxi 
Published: October 2022

Abstract
Background
The human endometrium is a highly regenerative tissue that is believed to have two main types of stem cells: endometrial mesenchymal/stromal stem cells (eMSCs) and endometrial epithelial stem cells (eESCs). So far, eMSCs have been extensively studied, whereas the studies of eESCs are constrained by the inability to culture and expand them in vitro. The aim of this study is to establish an efficient method for the production of eESCs from human endometrium for potential clinical application in intrauterine adhesion (IUA).

Results
Here we developed a culture condition with a combination of some small molecules for in vitro culturing and expansion of human SSEA-1+ cells. The SSEA-1+ cells exhibited stem/progenitor cell activity in vitro, including clonogenicity and differentiation capacity into endometrial epithelial cell-like cells. In addition, the SSEA-1+ cells, embedded in extracellular matrix, swiftly self-organized into organoid structures with long-term expansion capacity and histological phenotype of the human endometrial epithelium. Specifically, we found that the SSEA-1+ cells showed stronger therapeutic potential than eMSCs for IUA in vitro. In a rat model of IUA, in situ injection of the SSEA-1+ cells-laden chitosan could efficiently reduce fibrosis and facilitate endometrial regeneration.

Conclusions
Our work demonstrates an approach for isolation and expansion of human eESCs in vitro, and an appropriate marker, SSEA-1, to identify eESCs. Furthermore, the SSEA-1+ cells-laden chitosan might provide a novel cell-based approach for IUA treatment. These findings will advance the understanding of pathophysiology during endometrial restoration which may ultimately lead to more rational clinical practice.

Graphical Abstract
DLC1 deficiency at diagnosis predicts poor prognosis in acute myeloid leukemia
Authors: Li Xueqian , Qi Jiaqian , Song Xiaofei , Xu Xiaoyan , Pan Tingting , Wang Hong , Yang Jingyi , Han Yue 
Published: October 2022

AbstractAcute myeloid leukemia (AML) is a complex, heterogeneous malignant hematologic disease. Although multiple prognostic-related genes gave been explored in previous studies, there are still many genes whose prognostic value remains unclear. In this study, a total of 1532 AML patients from three GEO databases were included, five genes with potential prognostic value (DLC1, NF1B, DENND5B, TANC2 and ELAVL4) were screened by weighted gene co-expression network analysis (WGCNA), least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE). Based on this, we conducted survival analysis of the above five genes through the TCGA database and found that low level of DLC1 was detrimental to the long-term prognosis of AML patients. We also performed external validation in 48 AML patients from our medical center to analyze the impact of DLC1 level on prognosis. In conclusion, DLC1 may be a potential marker affecting the prognosis of AML, and its deficiency is associated with poor prognosis.
Co-occurring psychotic and eating disorders in England: findings from the 2014 Adult Psychiatric Morbidity Survey
Authors: Rodgers Ellen , Marwaha Steven , Humpston Clara 
Published: October 2022

Abstract
Background
Psychotic disorders and eating disorders are complex mental illnesses associated with increased mortality and functional impairment. This study aimed to investigate the co-occurrence and relationships between eating disorders and psychotic disorders and assess the mediation effect of mood instability.

Methods
This study used data from the Adult Psychiatric Morbidity Survey (APMS) 2014, a general population-based survey in England. Participants (total N = 7546, female N = 4488, male N = 3058, mean age = 52.3 years) were categorised based on psychotic disorder status into the groups of probable psychosis, diagnosed psychosis, and healthy controls without psychosis. The dependent variable of this study was the presence or absence of an eating disorder, with mood instability as the mediator. Logistic regression and mediation analyses were conducted to assess the relationships between these variables.

Results
Both probable and diagnosed psychoses were significantly related to the presence of an eating disorder, and mood instability was found to be a mediating variable with moderate effect.

Conclusion
The present study demonstrates a significant relationship between eating disorders and psychotic disorders in the English general population, indicating higher levels of co-occurrence between these two groups of disorders than when compared with healthy controls. The findings also suggest the relationship between eating and psychotic disorders is mediated, to an extent, by the presence of mood instability traits. Future research could extend the present study’s findings through assessing whether specific eating disorders are more significantly related to psychotic disorders than others.
Exploring the role of language knowledge and background knowledge in reading comprehension of specific-purpose tests in higher education
Authors: Tarlani-Aliabadi Hasan , Tazik Khalil , Azizi Zeinab 
Published: October 2022

AbstractThough the empirical findings of the past studies in the literature have offered strong support to the significant role of language knowledge and background knowledge in reading comprehension, this issue has not been explored with regard to specific purposes tests in the Iranian higher education context. Therefore, this study aimed at exploring the interaction effects between language knowledge and background knowledge among Iranian university students majoring in economics. For this purpose, a total of 90 students including male students (n = 35) and female students (n = 55) majoring in economics were selected through a convenience sampling method. Having been divided into three proficiency levels, they took three high-stakes reading tests constructed by the National Organization of Educational Testing in Iran for Economics candidates. Based on three criteria, including sentences with passive, Flesch Readability Index, and sentences with participles as attributes, the three texts were ranked in order of easy to difficult (text 1, text 2, and text 3). Afterward, 15 participants participated in semi-structured interviews to express their experiences with the reading tests. The results indicated that background knowledge had marked effects on the performances of the participants across the three reading texts. However, in the more specific reading text (text 3), neither general language knowledge nor general background knowledge were strong indicators. Additionally, the results of the semi-structured interviews with the participants revealed they lacked the required language and content knowledge to perform well on the reading text 3. In light of the findings, a range of implications is proposed for pertinent stakeholders.
Virtual reconstruction of the painting process and original colors of a color-changed Northern Wei Dynasty mural in Cave 254 of the Mogao Grottoes
Authors: Bolong Chai , Zongren Yu , Manli Sun , Zhongwei Shan , Jinli Zhao , Biwen Shui , Zhuo Wang , Yaopeng Yin , Bomin Su 
Published: October 2022

Abstract
The Northern Wei Dynasty (386–534 CE) murals of Cave 254 in the Mogao Grottoes, China, have been extensively affected by pigment color changes and fading. These issues severely hinder efforts to correctly understand the value and painting process of murals from this historic period. The virtual reconstruction of the faded murals reflects the analysis results of the pigments applied during the painting process and provides a new direction for conservation and art research. However, simple virtual reconstructions may not be accurate owing to deficiencies in our understanding of the color-changed pigments and fading of image lines. In this study, multi-band imaging (MSI) was performed to obtain infrared-reflected false color, ultraviolet-reflected false color, and ultraviolet luminescence images of the mural. A portable X-ray fluorescence spectrometer, portable digital microscope, scanning electron microscope, energy dispersive X-ray spectrometer, liquid chromatography–mass spectrometer, and confocal Raman microscope were used. Non-invasive and minimally invasive analyses of local portions of different color areas were performed to identify their pigments and map the strata, and a hue–saturation–brightness palette was constructed for these pigments. Finally, the pigment analysis results were combined with the multi-band image features to determine the pigment distribution of the mural, which was then used to virtually reconstruct the original color and appearance of the faded mural under ideal conditions. This study is the first to use a virtual reconstruction based on objective analyses to simulate the original color, painting processes, and pigment stratigraphy of a mural from the Northern Wei Dynasty. A preliminary discussion of the relationship between the painting processes of the mural and color changes in its pigments was also performed. The findings of this study will provide new perspectives on the study of Northern Wei Dynasty murals.
High-resolution metabolomics-based biomarker discovery using exhaled breath condensate from patients with lung cancer
Authors: Bang Geul , Park Ji Hyun , Park Changyoung , Kim Kwan-joong , Kim Jae Kwan , Lee Sung Yong , Kim Jin Young , Park Youngja Hwang 
Published: October 2022

AbstractEarly diagnosis and treatment are critical for improving the survival of patients with lung cancer, which is the leading cause of cancer-related deaths worldwide. In this study, we investigated whether the metabolomics analysis of exhaled breath condensate (EBC) from patients with lung cancer can provide biomarkers that can be used for noninvasive screening for lung cancer diagnosis. EBC samples obtained from patients with lung cancer (n = 20) and healthy individuals (n = 5) were subjected to high-resolution metabolomics (HRM) using liquid chromatography–mass spectrometry (LC–MS). Univariate analysis, with a false discovery rate (FDR), q = 0.05, and hierarchical clustering analysis were performed to discover significantly different metabolites between the healthy controls and patients with lung cancer. This was followed by the identification of the metabolites using the METLIN database. Pathway analysis based on the identified metabolites revealed that arachidonic acid (AA) metabolism was the most significantly affected pathway. Finally, 5-hydroxyicosatetraenoic acid (HETE) (m/z 343.2233, [M + Na]+), a metabolite involved in AA metabolism, was found to be significantly higher in patients with lung cancer than in healthy counterparts. Our finding suggested that the HRM of EBC samples is a useful approach for identifying biomarkers for noninvasive screening for lung cancer diagnosis.
Present status of renal replacement therapy in lower-middle-income Asian countries: Cambodia, Myanmar, Laos, Vietnam, Mongolia, and Bhutan as of June 2019 (before COVID-19), from the interviews of leading doctors in every country: (duplicated English publication from “the special Japanese edition of educational lectures in the 64th annual meeting of the Japanese Society for Dialysis Therapy”)
Authors: Hyodo Toru , Yamashita Akihiro C. , Hirawa Nobuhito , Isaka Yoshitaka , Nakamoto Hidetomo , Shigematsu Takashi 
Published: October 2022

AbstractThe present status of Cambodia, Myanmar, Laos, Vietnam, Mongolia, and Bhutan as of June 2019 was reviewed from the interviews of leading doctors in every country. The timing was until just 6 months before the COVID-19 pandemic broke out. The cost per hemodialysis session was 25–70 US dollar and expensive if it is compared with average monthly income of every country. In Cambodia and Laos, patients must cover 100% of expenses for maintenance hemodialysis, in Myanmar, the government covers the cost of once-weekly dialysis sessions, in Vietnam, the government covers 80% of the cost, and in Mongolia and Bhutan, the cost is fully covered by the government. Continuous ambulatory peritoneal dialysis was widely available in Vietnam and Mongolia, which have achieved a relative standard of social infrastructure, but is far from common in any of the other countries. The number of patients on dialysis is increasing with economic development in all countries. Diabetic nephropathy is a common primary reason for dialysis. None of the countries discussed in this article had clinical engineers who could maintain hemodialysis equipment and carry out clinical tasks in dialysis centers. Hospitals were not maintaining their equipment, and damaged units were kept in storage to be used for spare parts. None of the countries had dieticians to provide patients with dietary guidance. Establishment and training of both clinical engineers and registered dietitians are major projects that must be undertaken.