bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell-free DNA measurable residual disease as a predictor of postallogeneic hematopoietic cell transplant outcomes
Authors: Pasca Sergiu , Guo Matthew Z. , Wang Shiyu , Stokvis Kristin , Shedeck Audra , Pallavajjala Aparna , Shams Cynthia , Pallavajjala Roshni , DeZern Amy E. , Varadhan Ravi , Gocke Christopher D. , Jones Richard J. , Gondek Lukasz P. 
Published: June 2023

Abstract
The measurable residual disease (MRD) assessment provides an attractive predictor of allogeneic hematopoietic cell transplnat (alloHCT) outcomes. Cell-free DNA (cfDNA) has been applied to diagnosis, early detection, and disease burden monitoring in various tumors, but its utility as an MRD test in myeloid malignancies has not been systematically evaluated. We sought to determine the differential sensitivity between bone marrow (BM) and cfDNA MRD and to assess the effect of cfDNA MRD on alloHCT outcomes. The technical and clinical validation cohorts, including 82 patients participating in clinical trials (Bone Marrow Transplant Clinical Trials Network-0201 and 0402), were used. Ultradeep error-corrected targeted sequencing was performed on plasma and BM-derived DNA. We demonstrated that 94.6% (range, 93.9-95.3) of cfDNA was derived from hematopoietic tissue. The mutant allele fraction was congruent between BM and cfDNA (rho = 0.8; P &lt; .0001); however, cfDNA seemed to be more sensitive in detecting clones with a variant allele frequency (VAF) of &lt;0.26%. cfDNA-MRD clearance by day 90 after alloHCT (D90) was associated with improved relapse-free survival (RFS, median survival not reached vs 5.5 months; P &lt; .0001) and overall survival (OS, median survival not reached vs 7.3 months; P &lt; .0001) when compared with patients with persistent MRD. Irrespective of pre-alloHCT MRD, D90 cfDNA MRD was associated with inferior 2-year OS (16.7% vs 84.8%; P &lt; .0001) and RFS (16.7% vs 80.7%; P &lt; .0001). cfDNA seems to be an accurate, minimally invasive alternative to BM aspirates in MRD assessment and confers important prognostic implications in patients with myeloid malignancies undergoing alloHCT.
PACAP6-38 improves nitroglycerin-induced central sensitization by modulating synaptic plasticity at the trigeminal nucleus caudalis in a male rat model of chronic migraine
Authors: Zhang Lily , Zhou Yanjie , Yang Liu , Wang Yue , Xiao Zheman 
Published: June 2023

Abstract
Aims
Chronic migraine (CM) is a common neurological disorder with complex pathogenesis. Evidence suggests that pituitary adenylate cyclase-activating peptide (PACAP) induces migraine-like attacks and may be potential a new target for migraine treatment, but the therapeutic results of targeting PACAP and its receptors are not uniform. Therefore, the aim of this study was to investigate the regulatory effect of PACAP type I receptor (PAC1R) antagonist, PACAP6-38, on nitroglycerin (NTG)-induced central sensitization in a CM model.

Methods
Sprague–Dawley (SD) rats received repeated injections of NTG to construct a CM model. Mechanical and thermal thresholds were measured using Von Frey filaments and hot plate tests. C-Fos expression was measured by western blotting and immunofluorescence staining to assess the central sensitization. PACAP6-38 was intracerebrally injected into the trigeminal nucleus caudalis (TNC), and then the changes in c-Fos, the synaptic-associated proteins, phospho-ERK1/2 (p-ERK1/2), phosphorylation of cyclic adenosine monophosphate response element-binding protein (p-CREB) and brain-derived neurotrophic factor (BDNF) were detected. Transmission electron microscopy (TEM) and Golgi-Cox staining were used to observe the ultrastructure of synapses and dendritic structures of TNC neurons.

Results
The results showed that PACAP and PAC1R expression were significantly raised in the TNC after repeated NTG injections. Additionally, PACAP6-38 treatment alleviated nociceptive sensitization, inhibited NTG-induced overexpression of c-Fos and synaptic-associated proteins in the TNC of CM rat, restored aberrant synaptic structures. Furthermore, the expression of ERK/CREB/BDNF pathway was depressed by PACAP6-38.

Conclusions
Our results demonstrated that abnormal synaptic structure in the TNC of CM, which could be reversed by inhibition of PAC1R via down-regulating the ERK/CREB/BDNF signaling pathway. PACAP6-38 improves NTG-induced central sensitization by regulating synaptic plasticity in the TNC of CM rat, which may provide new insights into the treatments targeting PACAP/PAC1R in migraine.
The predictive value of CD4, CD8, and C—reactive protein in the prognosis of schistosomal and non-schistosomal colorectal cancer
Authors: Cheng Meihong , Jing Hongyan , Bu Dacheng , Liu Jing , Lu Kui , Liu Jican , Xu Yanchao , Zhu Ting , Hou Yingyong , Yao Junxia , Zhai Qilin , Wang Weixia 
Published: June 2023

Abstract
Background
Although schistosomiasis has been basically eliminated, it has not been completely extinction in China and occasional outbreaks occur in Europe in recent years. The relationship between inflammation caused by Schistosoma japonicum and colorectal cancer (CRC) is still obscure, and the inflammation based prognostic systems of schistosomal colorectal (SCRC) has rarely been reported.

Aim
To explore the different roles of tumor infiltrating lymphocytes (TILs) and C-reactive protein (CRP) in SCRC and in Non-schistosomal CRC (NSCRC), providing a possible predictive system to evaluate outcomes and to improve the risk stratification for CRC patients, especially for CRC patients with schistosomiasis.

Methods
Three hundred fifty-one CRC tumors were evaluated for density of CD4 + , CD8 + T cells and CRP in intratumoral and stromal compartments by immunohistochemical using tissue microarray.

Results
There were no association between TILs and CRP and schistosomiasis. Multivariate analysis identified stromal CD4 (sCD4) (p = 0.038), intratumoral CD8 (iCD8) (p = 0.003), schistosomiasis (p = 0.045) as independent prognostic factors for overall survival (OS) in the whole cohort; and sCD4 (p = 0.006) and iCD8 (p = 0.020) were independent prognostic factors for OS in the NSCRC and SCRC set, respectively. Besides, we found that there were no differences of TILs and CRP, which were distributed in different areas of tumor tissue, between CRC patients with and without schistosomiasis.

Conclusion
The results remind us that different subtypes of TILs have distinguished biological behavior and prognosis value in the immune microenvironment of NSCRC and SCRC patients. Meanwhile, the findings require us to stratify patients with schistosomiasis and this might facilitate patient counseling and management.
Determinants of physical, psychological, and social well-being in older adults: a cross-sectional study in senior care facilities of Pakistan (2019/20)
Authors: Tariq Jawad , Zakar Rubeena , Ali Mohammad Vaqas , Zakar Muhammad Zakria , Sajjad Amal , Fischer Florian 
Published: June 2023

Abstract
Background
Published research on senior care facilities in Pakistan is scarce and no large-scale study has been conducted to assess factors affecting well-being of older adults in these facilities. This study, therefore, investigated the effects of relocation autonomy, loneliness, and satisfaction with services along with socio-demographic characteristics on physical, psychological, and social well-being of older residents living in senior care facilities of Punjab, Pakistan.

Methods
This cross-sectional study collected data from 270 older residents living in 18 senior care facilities across 11 districts of Punjab, Pakistan from November 2019 to February 2020 using multistage random sampling. Existing reliable and valid scales were used to collect information from older adults related to relocation autonomy (Perceived Control Measure Scale), loneliness (de Jong-Gierveld Loneliness Scale), satisfaction with service quality (Service Quality Scale), physical and psychological well-being (General Well-Being Scale), and social well-being (Duke Social Support Index). A psychometric analysis of these scales was carried out followed by three separate multiple regression analyses to predict physical, psychological, and social well-being from socio-demographic variables and key independent variables (relocation autonomy, loneliness, and satisfaction with service quality).

Results
The results of multiple regression analyses showed that the models predicting physical (R2 = 0.579), psychological (R2 = 0.654), and social well-being (R2 = 0.615) were statistically significant (p < 0.001). Number of visitors was a significant predictor of physical (b = 0.82, p = 0.01), psychological (b = 0.80, p < 0.001), and social (b = 2.40, p < 0.001) well-being. Loneliness significantly predicted physical (b = -0.14, p = 0.005), psychological (b = -0.19, p < 0.001), and social (b = -0.36, p < 0.001) well-being. Control over relocation process significantly predicted physical (b = 0.56, p < 0.001) and psychological (b = 0.36, p < 0.001) well-being. Satisfaction with services significantly predicted physical (b = 0.07, p < 0.001) and social (b = 0.08, p < 0.001) well-being.

Conclusion
Pragmatic, equitable and cost-effective interventions are needed to improve the wellbeing of older residents living in senior care facilities. Friendly behavior of mobilizing staff and adjusted residents to facilitate new residents, therapeutic interventions such as relocation support programs, reminiscence therapy and intergenerational support, and increasing their exposure and connection to the outside world, can raise their physical, psychological, and social well-being.
Influence of the use of social media on patients changing dental practice: a web-based questionnaire study
Authors: Freire Yolanda , Sánchez Margarita Gómez , Suárez Ana , Joves Gerardo , Nowak Marlen , Díaz-Flores García Víctor 
Published: June 2023

Abstract
Background
Recent years have seen an increase in the use of social media, by the healthcare sector, including dentistry. Indeed, social media may now be important communication tools for dental practices and patients.
This work analyzes the influence of patient (male and female) use of dental practice social media on their decision to change practice. The results also provide insight into the factors patients considered important when choosing a dental practice.

Methods
This study was approved by the Ethics Committee of the Universidad Europea de Madrid (No. CIPI/22.022). Using a web-based questionnaire, a cross-sectional study was undertaken involving a Spanish population that made use of dental services. The questionnaire consisted of four parts covering provision of informed consent, the collection of sociodemographic data, patient use of dental practice social media, and the factors considered important when changing dental practice.

Results
All participants gave their informed consent regarding inclusion. No compensation was provided for participation. 588 people responded to the questionnaire, of whom 503 were eligible for inclusion. Most respondents were female (312/503; 62%). Most (151/503; 30%) last changed dental practice during the previous 2–5 years. 208/503 (41.4%) indicated that they had visited dental practice social media. 118/503 (23.5%) indicated that they had made use of such the last time they changed dental practice; 102 of these 118 (85.6%) reported their experience to have influenced their decision to change. Respondents who had changed practice in the last 5 years had interacted with dental practice social media more than those who changed over 11 years ago (p < .05), and those who changed practice in the present/past year were more influenced by these media (p < .05). The factor considered most important was 'Facilities and technology'. No gender-based differences were seen for any measured variable (p < .05).

Conclusions
Different factors affect the selection of a new dental practice, but respondents who changed practice in the last few years were more likely to have made use of dental practice social media, which, for some, influenced their final decision to change. Dental practices might do well to consider using social media as communication and marketing tools.
A qualitative study examining the critical differences in the experience of and response to formative feedback by undergraduate medical students in Japan and the UK
Authors: Kozato An , Shikino Kiyoshi , Matsuyama Yasushi , Hayashi Mikio , Kondo Satoshi , Uchida Shun , Stanyon Maham , Ito Shoichi 
Published: June 2023

Abstract
Background
Formative feedback plays a critical role in guiding learners to gain competence, serving as an opportunity for reflection and feedback on their learning progress and needs. Medical education in Japan has historically been dominated by a summative paradigm within assessment, as opposed to countries such as the UK where there are greater opportunities for formative feedback. How this difference affects students’ interaction with feedback has not been studied. We aim to explore the difference in students’ perception of feedback in Japan and the UK.

Methods
The study is designed and analysed with a constructivist grounded theory lens. Medical students in Japan and the UK were interviewed on the topic of formative assessment and feedback they received during clinical placements. We undertook purposeful sampling and concurrent data collection. Data analysis through open and axial coding with iterative discussion among research group members was conducted to develop a theoretical framework.

Results
Japanese students perceived feedback as a model answer provided by tutors which they should not critically question, which contrasted with the views of UK students. Japanese students viewed formative assessment as an opportunity to gauge whether they are achieving the pass mark, while UK students used the experience for reflective learning.

Conclusions
The Japanese student experience of formative assessment and feedback supports the view that medical education and examination systems in Japan are focused on summative assessment, which operates alongside culturally derived social pressures including the expectation to correct mistakes. These findings provide new insights in supporting students to learn from formative feedback in both Japanese and UK contexts.
Associations among leadership, resources, and nurses’ work engagement: findings from the fifth korean Working Conditions Survey
Authors: Kim Eunkyung , Lee Ji Yea , Lee Seung Eun 
Published: June 2023

Abstract
Background
Nurses’ work engagement has received extensive attention due to its positive impacts on individual and organizational outcomes, including patient safety and quality care in healthcare organizations. Although nurse managers’ leadership and a variety of resources have been identified as important factors of nurses’ work engagement, these relationships have not been well understood in Korean nursing contexts. The purpose of this study was to examine the associations among nurse managers’ leadership, resources, and work engagement among Korean nurses after controlling for nurses’ demographic and work-related characteristics.

Methods
This is a cross-sectional study using data from the fifth Korean Working Conditions Survey. Using a sample of 477 registered nurses, we employed hierarchical linear regression analyses. Nurse managers’ leadership, job resources (organizational justice and support from peers), professional resources (employee involvement), and personal resources (meaning of work) were examined as potential predictors of nurses’ work engagement.

Results
We found that nurse managers’ leadership (β = 0.26, 95% confidence interval [CI] = 0.17–0.41) was the strongest predictor of nurses’ work engagement, followed by meaning of work (β = 0.20, 95% CI = 0.07–0.18), organizational justice (β = 0.19, 95% CI = 0.10–0.32), and support from peers (β = 0.14, 95% CI = 0.04–0.23). Employee involvement was not a statistically significant predictor of nurses’ work engagement (β = -0.07, 95% CI = -0.11–0.01).

Conclusions
Our findings suggest that comprehensive approaches are required to promote nurses’ work engagement. Considering that nurse managers’ leadership was the strongest predictor of nurses’ work engagement, nurse managers should demonstrate supportive leadership behaviors such as acknowledging and praising their unit nurses’ work performance. Furthermore, both individual- and organizational-level strategies are necessary for nurses to be engaged at work.
Associations between long-term care-service use and service- or care-need level progression: a nationwide cohort study using the Japanese Long-Term Care Insurance Claims database
Authors: Hasegawa Kohei , Tsukahara Teruomi , Nomiyama Tetsuo 
Published: June 2023

Abstract
Background
The effectiveness of the long-term care service in Japan has been unclear, and most of the relevant studies of this service have been limited to a single region and relatively small samples, necessitating large-scale studies. We examined the associations between long-term care service use and the service/care-need level progression at the national scale in Japan.

Methods
We conducted a nationwide retrospective cohort study using data from the Japanese Long-Term Care Insurance Claims database. Individuals aged ≥ 65 years and newly certified as being at the support-need level 1 or 2 or the care-need level 1 between April 2012 and March 2013 were included. We first conducted 1:1 propensity score matching and then examined the associations between service use and the progression in support-need or care-need levels by using Kaplan–Meier survival curves and log-rank tests.

Results
The final sample consisted of 332,766 individuals. We observed that service use was associated with a faster decline in the support/care-need level, although the differences in the subjects' survival rate diminished; the log-rank test showed significance (p < 0.001). When stratified for urban–rural classifications or regions of Japan, the results were similar to the primary analysis in all of the stratified groups, and no clear regional variations were observed.

Conclusion
We did not observe a clear beneficial effect of receiving long-term care in Japan. Our results suggest that Japan's current long-term care service may not be effective for the recipients of these services. Considering that the system is becoming a financial burden, a re-examination of the service to provide more cost-effective care may be advisable.
Metabolomics analysis of the potential mechanism of Yi-Guan-Jian decoction to reverse bone loss in glucocorticoid-induced osteoporosis
Authors: Yin Mengxing , Zhou Dezhi , Jia Fu , Su Xiaosan , Li Xiufang , Sun Ruifen , Li Junmin 
Published: June 2023

Abstract
Background
Glucocorticoid-induced osteoporosis (GIOP) is a disease in which long-term use of glucocorticoid causes bone loss, deterioration of bone microstructure and fracture. Currently, clinical drugs targeting this disease have certain side effects. There is still a need to find effective drugs with fewer side effects. The theory of traditional Chinese medicine suggests that YGJ has therapeutic effect on GIOP, but it has not been explained. Therefore, this study aims to explore the protective effect of YGJ on GIOP mouse models and elucidate the underlying mechanism through LC–MS-based metabolomics analysis.

Methods
The general condition of 8 week age male C57BL/6J mice was recorded after 8 weeks of treatment with dexamethasone (DEX) and YGJ. Bone-related parameters and bone morphology were determined by Micro-CT. HE staining was used to observe the pathological changes of bone tissue. Serum levels of bone metabolism markers were detected by ELISA. Liver metabolomics analysis was conducted to search for the significant markers of anti-GIOP of YGJ and the metabolic pathway affecting it.

Results
After treatment, YGJ significantly reversed the weight loss caused by DEX; increase the number of bone trabecular in ROI region, significantly improve the bone-related parameters of GIOP mice, and increase the levels of alkaline phosphatase and osteocalcin. In the study of metabolic mechanism, YGJ reversed 24 potential markers in GIOP mice. These included cortisol, 3-hydroxybutyric acid, taurine, esculin and uric acid, which are closely associated with osteoporosis. Topological analysis results showed that YGJ had the most significant effect on taurine and hypotaurine metabolism, with − log10 (P) > 2.0 and Impact > 0.4.

Conclusions
Yi-Guan-Jian decoction can increase bone density and improve bone microstructure by regulating the levels of alkaline phosphatase and osteocalcin and reverse bone loss in GIOP mouse model. The underlying metabolic mechanism may be related to taurine and hypotaurine metabolic pathway.
Preimplantation genetic testing for Aicardi–Goutières syndrome induced by novel compound heterozygous mutations of TREX1: an unaffected live birth
Authors: Xu Huiling , Pu Jiajie , Lin Suiling , Hu Rui , Yao Jilong , Li Xuemei 
Published: June 2023

Abstract
Background
Aicardi–Goutières syndrome (AGS) is a rare, autosomal recessive, hereditary neurodegenerative disorder. It is characterized mainly by early onset progressive encephalopathy, concomitant with an increase in interferon-α levels in the cerebrospinal fluid. Preimplantation genetic testing (PGT) is a procedure that could be used to choose unaffected embryos for transfer after analysis of biopsied cells, which prevents at-risk couples from facing the risk of pregnancy termination.

Methods
Trio-based whole exome sequencing, karyotyping and chromosomal microarray analysis were used to determine the pathogenic mutations for the family. To block the inheritance of the disease, multiple annealing and looping-based amplification cycles was used for whole genome amplification of the biopsied trophectoderm cells. Sanger sequencing and next-generation sequencing (NGS)-based single nucleotide polymorphism (SNP) haplotyping were used to detect the state of the gene mutations. Copy number variation (CNV) analysis was also carried out to prevent embryonic chromosomal abnormalities. Prenatal diagnosis was preformed to verify the PGT outcomes.

Results
A novel compound heterozygous mutation in TREX1 gene was found in the proband causing AGS. A total of 3 blastocysts formed after intracytoplasmic sperm injection were biopsied. After genetic analyses, an embryo harbored a heterozygous mutation in TREX1 and without CNV was transferred. A healthy baby was born at 38th weeks and prenatal diagnosis results confirmed the accuracy of PGT.

Conclusions
In this study, we identified two novel pathogenic mutations in TREX1, which has not been previously reported. Our study extends the mutation spectrum of TREX1 gene and contributes to the molecular diagnosis as well as genetic counseling for AGS. Our results demonstrated that combining NGS-based SNP haplotyping for PGT-M with invasive prenatal diagnosis is an effective approach to block the transmission of AGS and could be applied to prevent other monogenic diseases.