bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of H3K9me3 and DNA methylation co-marked CpG-rich regions during mouse development
Authors: Yang Hui , Wang Yiman , Zhang Yong 
Published: November 2023

Abstract
Background
H3K9me3 and DNA methylation co-marked CpG-rich regions (CHMs) are functionally important in mouse pre-implantation embryos, but their characteristics in other biological processes are still largely unknown.

Results
In this study, we performed a comprehensive analysis to characterize CHMs during 6 mouse developmental processes, identifying over 2,600 CHMs exhibiting stable co-mark of H3K9me3 and DNA methylation patterns at CpG-rich regions. We revealed the distinctive features of CHMs, including elevated H3K9me3 signals and a significant presence in euchromatin and the potential role in silencing younger long terminal repeats (LTRs), especially in some ERVK subfamilies. The results highlight the distinct nature of universal CHMs compared to CpG-rich nonCHMs in terms of location, LTR enrichment, and DNA sequence features, enhancing our understanding of CpG-rich regions' regulatory roles.

Conclusions
This study characterizes the features of CHMs in multiple developmental processes and broadens our understanding of the regulatory roles of CpG-rich regions.
Enhancing powdery mildew resistance in soybean by targeted mutation of MLO genes using the CRISPR/Cas9 system
Authors: Bui Thao Phuong , Le Huy , Ta Dong Thi , Nguyen Cuong Xuan , Le Ngoc Thu , Tran Truong Thi , Van Nguyen Phuong , Stacey Gary , Stacey Minviluz G. , Pham Ngoc Bich , Chu Ha Hoang , Do Phat Tien 
Published: November 2023

Abstract
Background
Powdery mildew is a major disease that causes great losses in soybean yield and seed quality. Disease-resistant varieties, which are generated by reducing the impact of susceptibility genes through mutation in host plants, would be an effective approach to protect crops from this disease. The Mildew Locus O (MLO) genes are well-known susceptibility genes for powdery mildew in plant. In this study, we utilized the CRISPR/Cas9 system to induce targeted mutations in the soybean GmMLO genes to improve powdery mildew resistance.

Results
A dual-sgRNA CRISPR/Cas9 construct was designed and successfully transferred into the Vietnamese soybean cultivar DT26 through Agrobacterium tumefaciens-mediated transformation. Various mutant forms of the GmMLO genes including biallelic, chimeric and homozygous were found at the T0 generation. The inheritance and segregation of CRISPR/Cas9-induced mutations were confirmed and validated at the T1 and T2 generations. Out of six GmMLO genes in the soybean genome, we obtained the Gmmlo02/Gmmlo19/Gmmlo23 triple and Gmmlo02/Gmmlo19/Gmmlo20/Gmmlo23 quadruple knockout mutants at the T2 generation. When challenged with Erysiphe diffusa, a fungus that causes soybean powdery mildew, all mutant plants showed enhanced resistance to the pathogen, especially the quadruple mutant. The powdery mildew severity in the mutant soybeans was reduced by up to 36.4% compared to wild-type plants. In addition, no pleiotropic effect on soybean growth and development under net-house conditions was observed in the CRISPR/Cas9 mutants.

Conclusions
Our results indicate the involvement of GmMLO02, GmMLO19, GmMLO20 and GmMLO23 genes in powdery mildew susceptibility in soybean. Further research should be conducted to investigate the roles of individual tested genes and the involvement of other GmMLO genes in this disease infection mechanism. Importantly, utilizing the CRISPR/Cas9 system successfully created the Gmmlo transgene-free homozygous mutant lines with enhanced resistance to powdery mildew, which could be potential materials for soybean breeding programs.
Gaps in vaccine management practices during vaccination outreach sessions in rural settings in southwestern Uganda
Authors: Flavia Atwiine , Fred Bagenda , Eleanor Turyakira 
Published: November 2023

Abstract
Background
Outreach efforts were developed to bolster people’s access to and use of immunization services in underserved populations. However, there have been multiple outbreaks of diseases like measles in Uganda, prompting policy makers and stakeholders to ask many unanswered questions. This research study was created to uncover the discrepancies between vaccine management practices at immunization outreach sessions in rural South Western Uganda compared with existing standards.

Methods
The observational qualitative study, was done in 16 public health facilities across four districts of Uganda. Data were collected using in-depth interviews, facility record reviews, and observation. We assessed the vaccine management procedures before immunization session, transportation used, set up at the outreach site, management practices during the outreach session and packing of vaccines - according to World Health Organization immunization practice recommendations. The data were transcribed, coded and categories were formed and triangulated. Themes were generated based on a socio-ecologic framework to gain a better understanding of healthcare provider practices during immunization sessions.

Results
Fifty-one individuals were interviewed; four Assistant District Health Officers, four cold chain technicians, 15 focal persons for the Expanded Program on Immunization, and 28 health care providers. The respondents’ mean age was 35, 43 (84.3%) were females and 24 (47.1%) had a diploma. 11 (69%) outreaches were conducted at a distance of 5-12 km from the health facility and 7 (44%) were conducted in a building. For 8 outreaches (50%) health facility staff did not check the vaccine vial monitor status before the outreach while 12(75%) did not keep the vaccine hard lid cover closed during the sessions. The main areas of concern were insufficient vaccine integrity monitoring, improper handling and storage practices, deficient documentation, and inadequate vaccine transportation. These were similar across immunization outreach sites regardless of vaccine preventable disease outbreaks occurrences. The majority of these gaps were located at the individual level but were enabled by policy/environmental factors.

Conclusions
There are poor vaccine management procedures during outreach sessions contrary to established guidelines. Specific tactics to tackle knowledge deficiencies, health worker attitude, and fewer equipment shortages could improve compliance to guidelines.
Long-term efficacy and stability of miniscrew-assisted rapid palatal expansion in mid to late adolescents and adults: a systematic review and meta-analysis
Authors: Zeng Weiqian , Yan Shuyun , Yi Yating , Chen Hao , Sun Tongke , Zhang Yimeng , Zhang Jun 
Published: November 2023

Abstract
Background
The purpose of this study is to investigate the long-term efficacy and stability of Miniscrew-assisted Rapid Palatal Expansion (MARPE), including its primary outcomes, namely the nasomaxillary complex transverse skeletal and dental expansion, and related secondary outcomes.

Methods
Electronic databases and manual literature searches, up to October 31, 2022, were performed. The eligibility criteria were the following: studies on patients with transverse maxillary deficiency treated with MARPE in adults and adolescents over 13.5 years of age.

Results
Ultimately, twelve articles were included in the analysis, one prospective and eleven retrospective observational studies. Five studies showed a moderate risk of bias, while the remaining seven studies were at a serious risk of bias. The GRADE quality of evidence was very low. MARPE is an effective treatment modality for transverse maxillary deficiency (mean success rate: 93.87%). Patients showed increased mean in the skeletal and dental transverse expansion. The basal bone composition, mean alveolar bone and mean dental expansion accounted for 48.85, 7.52, and 43.63% of the total expansion, respectively. There was a certain degree of skeletal and dental relapse over time. MARPE could also cause dental, alveolar, and periodontal side effects, and have an impact on other craniofacial bones, upper airway, and facial soft tissue.

Conclusions
MARPE is an effective treatment for transverse maxillary deficiency, with a high success rate and a certain degree of skeletal and dental relapse over time.
Identifying the predictors of turnover intention based on nurse managers’ toxic leadership behaviors among nurses in Iran: a cross-sectional correlational study
Authors: Nonehkaran Elham Ahangari , Mozaffari Naser , Iranpour Sohrab , Soola Aghil Habibi 
Published: November 2023

Abstract
Background
Unfavorable leadership practices are a growing concern in the field of healthcare and nursing that have adverse consequences on nurses’ career outcomes. One of the undesirable leadership styles is the toxic leadership style. Considering the importance of nursing managers’ leadership style and its impact on nurses’ performance and the scarcity of studies in this field, the present study was conducted to determine toxic leadership behaviors in nursing managers and their relationship with the turnover intention among nurses.

Methods
A multicenter cross-sectional correlational study. This study involved 551 nurses from 5 educational-medical centers in Ardabil province, north-western Iran. Three self-report scales, including The demographic and occupational information form, the Toxic Leadership Behaviors of Nurse Managers Scale (ToxBH-NM), and the turnover intention questionnaire were adopted for assessment purposes in this study. Data were analyzed using SPSS (Version 22) software using descriptive statistics, Pearson correlation coefficient test, t-test, ANOVA test, and multiple linear regression analysis.

Results
Overall, 551 nurses participated in this research. There was a significantly positive relationship between Turnover intention and Toxic leadership behavior Subscales (r = 0.475, p < 0.001). Furthermore, multiple linear regression analysis showed Toxic leadership behavior Subscales (Intemperate behavior, Narcissistic behavior, Self-promoting behavior, and Humiliating behavior), Hospital, unit, Age, and Marital status predict Turnover intention when other variables are controlled.

Conclusion
A leader who directly and indirectly adopts toxic behavior toward their employees destructively affects both individuals and organizations. Nurses who work for a manager exhibiting toxic leadership behaviors demonstrated higher turnover intention.
Does the second opinion directive in Germany reach the patient? A parallel-convergent mixed-methods study
Authors: May Susann , Könsgen Nadja , Glatt Angelina , Bruch Dunja , Muehlensiepen Felix , Mählmann Sonja , von Peter Sebastian , Pieper Dawid , Neugebauer Edmund , Prediger Barbara 
Published: November 2023

Abstract
Background
A Second Opinion Directive (SOD) was introduced in Germany in December 2018 for elective surgeries such as hysterectomy, tonsillotomy, tonsillectomy, and shoulder arthroscopy. The aim of the SOD is to avoid surgeries which are not medically induced and to support patients in their decision-making process. A physician who indicates an SOD-relevant procedure must inform the patient about the SOD and its specifications. At this time, it is not clear whether physicians provide information about the SOD to patients and whether and how the SOD is implemented in daily practice. Furthermore, nothing is known about how patients react when they are told that they have the right to seek a second opinion according to the SOD.

Methods
To assess this, we undertook a parallel-convergent mixed-methods study with a qualitative and quantitative phase. Qualitative data were analysed by structured qualitative content analysis and survey data were analysed descriptively.

Results
26 interviews were conducted with patients for whom one of the above-mentioned surgeries was indicated. In parallel, a questionnaire survey with 102 patients was conducted. The results show that the SOD is not implemented in Germany for the selected indications because patients were not informed as intended. At the same time, when the right to obtain a second opinion was explained, it seemed to have a positive effect on the physician-patient relationship from patients` perspective.

Conclusions
It is possible that there is a lack of information for physicians, which in turn leads to an information deficit for patients. Better information for physicians might be part of the solution, but a negative attitude towards the SOD might also result in the low education rate. Therefore, in addition, potential patients or even the general population should be better informed about the possibility of obtaining a second opinion.
A randomized trial evaluating the association between related gene polymorphism and nausea and vomiting induced by cisplatin multi-day chemotherapy
Authors: Jin Yilan , Chen Feng , Zhao Juan , Jiang Ying , Jin Gaowa , Zhang Zewei , Li Quanfu 
Published: November 2023

Abstract
Purpose
We aim to investigate the correlation between gene polymorphisms and cisplatin chemotherapy-induced nausea and vomiting (CINV), which was prevented by olanzapine or aprepitant triple antiemetic regimen.

Methods
Before chemotherapy, the blood samples of 89 malignant tumor patients who received multi-day chemotherapy with cisplatin were collected for sequencing and typing. As there were duplicate patients enrolled in different chemotherapy cycles, there were a total of 190 cases. The patients were divided into two groups randomly, who received the triple antiemetic regimen of olanzapine or aprepitant combined with 5-HT3RA and dexamethasone. The main evaluation indicators were the total protection (TP) rate in the acute phase (0–24 h), the delayed phase (25–120 h) and the overall phase (0-120 h).

Results
Univariate analysis was performed on genetic loci that reached H-W balance with TP. In the olanzapine group, increased TP in the acute phase was associated with HTR3A rs1176719 non-GG (P < 0.05) genotype etc. Increased TP in the delayed phase was associated with HTR3A rs1176719 non-GG (P < 0.05) genotype etc. In the aprepitant group, increased TP in the acute phase was associated with the MTHFR rs1801131 TT (P < 0.05) genotype etc. Increased TP in the delayed phase was associated with HTR3A rs1062613 CC (P < 0.05) genetype ect. Multivariate Logistic regression analysis showed that HTR3B rs7943062GG (P < 0.05) genotype etc. were correlated with increased TP in the delayed phase. MTHFR rs1801131TT genotype was associated with increased TP in the acute phase (P < 0.05) and delayed phase (P < 0.05).

Conclusion
This study found that gene polymorphisms, including HTR3B (rs1062613, rs1176719, rs2276303), HTR3B (rs45460698, rs7943062), HTR3C (rs6766410), ERCC1 (rs3212986), ERCC4 (rs744154) and MTHFR(rs1801131), may be independent prognostic factors for CINV.
Ipsilateral synchronous papillary renal neoplasm with reverse polarity and urothelial carcinoma in a renal transplant recipient: a rare case report with molecular analysis and literature review
Authors: Li Daosheng , Liu Fenfen , Chen Yiqian , Li Ping , Liu Yuyu , Pang Yu 
Published: November 2023

Abstract
Background
Renal transplant recipients (RTRs) have a 3- to 5-fold higher risk of developing malignant tumors than the general population, with new malignant tumors after transplantation considered to be the leading cause of death in RTRs. In pathological practice, it is rare for neoplasms with different histology to be located in the same organ. We report the first case of a synchronous papillary renal neoplasm with reverse polarity (PRNRP) and urothelial carcinoma (UC) in the ipsilateral kidney in an RTR. Molecular detection was conducted by next-generation sequencing.

Case presentation
A 68-year-old female suffered from uremia 19 years ago and underwent renal transplantation (RT) after receiving dialysis for 6 months. Hematuria occurred one month ago and an enhanced CT showed that there were two abnormal density foci in the middle and lower parts of the autologous left kidney. A laparoscopic left nephrectomy and ureterectomy were performed. Gross examination revealed a mass (I) in the left renal parenchyma, 2*1.8*1.5 cm in size, that protruded from the renal capsule, and a cauliflower-like mass (II), 5*2.5*2 cm in size, adjacent to the mass (I). Microscopic findings revealed these lesions were PRNRP and UC, respectively. PCR analysis revealed a KRAS gene mutation (G12D in exon 2) in the PRNRP, while NGS analysis revealed FGFR3 (S249C in exon 7) and KDM6A (Q271Ter in exon 10 and A782Lfs in exon 17) mutations in the UC.

Conclusions
We report here for the first time an extraordinarily rare case of synchronous renal tumors of a PRNRP and UC in the ipsilateral kidney of an RTR. We identified simultaneous KRAS, FGFR3, and KDM6A mutations in two different renal masses in the ipsilateral kidney. Pathologic assessment with comparative molecular analysis of mutational profiles facilitates tumor studies after RT and may be of great value in clinical management strategies.
Chronic pregabalin treatment protects against spreading depolarization and alters hippocampal synaptic characteristics in a model of familial hemiplegic migraine-type 1
Authors: Cain Stuart M. , Alles Sascha R. A. , Gopaul Ray , Bernier Louis-Philippe , Yung Andrew C. , Bauman Andrew , Yang Yi , Baker Glen B. , Kozlowski Piotr , MacVicar Brian A. , Snutch Terrance P. 
Published: November 2023

AbstractFamilial hemiplegic migraine type-1 (FHM-1) is a form of migraine with aura caused by mutations in the P/Q-type (Cav2.1) voltage-gated calcium channel. Pregabalin, used clinically in the treatment of chronic pain and epilepsy, inhibits P/Q-type calcium channel activity and recent studies suggest that it may have potential for the treatment of migraine. Spreading Depolarization (SD) is a neurophysiological phenomenon that can occur during migraine with aura by propagating a wave of silenced neuronal function through cortex and sometimes subcortical brain structures. Here, utilizing an optogenetic stimulation technique optimized to allow for non-invasive initiation of cortical SD, we demonstrate that chronic pregabalin administration [12 mg/kg/day (s.c.)] in vivo increased the threshold for cortical spreading depolarization in transgenic mice harboring the clinically-relevant Cav2.1S218L mutation (S218L). In addition, chronic pregabalin treatment limited subcortical propagation of recurrent spreading depolarization events to the striatum and hippocampus in both wild-type and S218L mice. To examine contributing underlying mechanisms of action of chronic pregabalin, we performed whole-cell patch-clamp electrophysiology in CA1 neurons in ex vivo brain slices from mice treated with chronic pregabalin vs vehicle. In WT mice, chronic pregabalin produced a decrease in spontaneous excitatory postsynaptic current (sEPSC) amplitude with no effect on frequency. In contrast, in S218L mice chronic pregabalin produced an increase in sEPSC amplitude and decreased frequency. These electrophysiological findings suggest that in FHM-1 mice chronic pregabalin acts through both pre- and post-synaptic mechanisms in CA1 hippocampal neurons to elicit FHM-1 genotype-specific inhibitory action. The results highlight the potential of chronic pregabalin to limit recurrent SD to subcortical brain structures during pathophysiological events in both the genetically-normal and FHM-1 brain. The work further provides insights into FHM-1 pathophysiology and the potential for chronic pregabalin treatment to prevent SD in migraineurs.
Rare variants in GPR3 in POI patients: a case series with review of literature
Authors: Ren Shuting , Zhang Feng , Shang Lingyue , Yang Xi , Pan Yuncheng , Zhang Xiaojin , Wu Yanhua 
Published: November 2023

Abstract
Background
Premature ovarian insufficiency (POI) is a highly heterogeneous disease, and up to 25% of the cases can be explained by genetic causes. G protein-coupled receptor 3 (GPR3) plays an important role in oocyte arrest, and Gpr3-deficient mice exhibited POI-like phenotypes.

Case presentation
We identified two heterozygous missense variants of GPR3: NM_005281: c.C973T (p.R325C) and c.G772A (p.A258T) in two sporadic Han Chinese POI cases through whole exome sequencing and genetic analysis. The two patients were diagnosed as POI in their late 20s, presenting elevated serum levels of follicle stimulating hormone and secondary amenorrhea. Both variants are very rare in the population databases of ExAC, gnomAD and PGG.Han. The affected amino acids are conserved across species and the mutated amino acids are predicted deleterious with bioinformatics prediction tools and the protein three-dimensional structure analysis.

Conclusions
It is the first report of rare GPR3 variants associated with POI women, providing an important piece of evidence for GPR3 as a candidate gene which should be screened in POI. This finding suggested the necessity of including GPR3 in etiology study and genetic counseling of POI patients.
Children and youth’s movement behaviours differed across phases and by geographic region throughout the COVID-19 pandemic in Nova Scotia, Canada: an explanatory sequential mixed-methods study
Authors: Campbell Julie E. , Stone Michelle R. , Mitra Raktim , Locke Maggie , MacDonald Cynthia , Preston Ashley , Feicht Rebecca A. , Rehman Laurene , Kirk Sara F. L. , Faulkner Guy , Tremblay Mark S. , Moore Sarah A. 
Published: November 2023

AbstractBackgroundLike many places globally, the health and well-being of children and youth living in Canada were significantly affected by the COVID-19 pandemic. Restricted access to the outdoors, schools, and public green spaces impacted children’s physical activity (PA), sedentary behaviour, and sleep. Restrictions changed throughout the pandemic, and children’s and youth’s movement behaviours may have been differentially affected based on time and place. This paper aimed to examine the impact of the COVID-19 pandemic on the movement behaviours of children and youth living in Nova Scotia (NS), Canada, over time and by geographic region using mixed methods.MethodsThis study employed an explanatory sequential mixed-methods design. Secondary data from three repeated cross-sectional surveys of parent-reported demographic, movement, and geographic data of 291 children and youth aged 5–17 years were analyzed. Spatial cluster analyses were applied to identify geographic concentrations of children and youth who were more or less likely to meet the moderate-vigorous PA (MVPA) guideline during the pandemic. Semi-structured interviews were conducted with 14 Nova Scotian parents to understand their perspectives on their child’s movement behaviours during the pandemic. Interviews were analyzed deductively based on quantitative results using reflexive thematic analysis.ResultsOur findings showed only 5.5% of children and youth were meeting all guidelines throughout the pandemic. Of the movement behaviours, screen time (ST) differed across the pandemic and by age and gender. Clusters of children and youth meeting the MVPA recommendation on fewer days were found in regions within NS’s three largest population centres (Truro, Sydney, and the Halifax Regional Municipality (HRM)), and clusters of those meeting the MVPA recommendation on more days were also identified in the HRM. From semi-structured interviews, themes indicated: (1) escaping screens during early parts of the COVID-19 pandemic and when weather was colder was hard; (2) having access to spaces to be active near the home helped facilitate children’s movement; and (3) higher socioeconomic status enabled more opportunities for movement.ConclusionOverall, fewer public health restrictions led to more favourable movement behaviours and spatial and sociodemographic factors may have been at play. Decision-makers should consider these factors when identifying strategies to keep children active during future health crises.