bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of spousal migration on perinatal healthcare utilization
Authors: Khan Angubeen Gul , West Heidi , Razzaque Abdur , Kuhn Randall
Published: June 2023

Over the last three decades, out-migration has become a stable source of income for more than 12 million Bangladeshis. Of those migrants, 90% are men. Due to patriarchal cultural norms in Bangladeshi society, the migration of a male spouse may have significant consequences for the social well-being and health of left-behind women. In this study, we examine the impact of external (out of country) and internal (rural to urban) spousal migration on the perinatal healthcare utilization of left-behind women. We used data from the 2012 Matlab Health and Socioeconomic Survey (MHSS2) to examine use of antenatal care, presence of a medically qualified attendant at birth, and delivery at a healthcare facility for live births that occurred between 2007 and 2014 for currently married women aged 15-45 (N = 1,458 births among 1,180 women). Adjusted regression models indicated that for births occurring to women with a migrant spouse, odds of receiving antenatal care were significantly higher (OR: 4.1 for births to women with a domestic urban migrant spouse and 4.6 for births to women with an international migrant spouse, p < 0.01). Spousal migration was not linked to having a medically qualified attendant at birth or delivery at a clinic or hospital. Results suggest that spousal migration may be beneficial for receiving health care during a pregnancy, but not for the type of attendant or place of delivery at birth.
Clinical outcomes of intraluminal Iodine-125 seed strand brachytherapy and percutaneous nephrostomy in patients with ureteral carcinoma
Authors: Bi Yonghua , Jiao Dechao , Zhang Jianhao , Wang Yang , Su Mengdan , Ren Jianzhuang , Han Xinwei
Published: June 2023

Background

We aimed to evaluate the safety and efficacy of intraluminal iodine-125 seed strand brachytherapy and percutaneous nephrostomy in patients with ureteral carcinoma.

Methods

From January 2014 to January 2023, 48 patients with ureteral cancer not suitable for surgical resection were enrolled. Iodine-125 seed strand was inserted in 26 patients under c-arm CT and fluoroscopic guidance (Group A), and 22 patients underwent percutaneous nephrostomy without seed strand (Group B). The clinical outcomes (technical success rate, tumor sizes, hydronephrosis Girignon grade, complications, objective response rate (ORR), disease control rate (DCR), and survival time) were evaluated and compared.

Results

A total of 53 seed strands were successfully inserted and replaced in Group A, with a technical success rate of 100%. No procedure-related death or severe complications occurred in both group. Migration of seed strand or drainage tube was the most common complication. The Girignon grade of hydronephrosis was significantly improved 1, 3 and 6 months after procedure in both groups. DCR in Group A were 96.2%, 80.0%, and 70.0% at 1-, 3-, and 6-month follow up, respectively. At 1 and 6 months later, ORR in Group A were significantly higher than those in Group B (p < 0.05). The median overall survival were 30.0 months in Group A and 16.1 months in Group B, respectively (p = 0.04). The median progression-free survival were 11.1 months in Group A and 6.9 months in Group B, respectively (p = 0.09).

Conclusion

Intraluminal Iodine-125 seed strand brachytherapy and percutaneous nephrostomy is safe and effective in patients with ureteral carcinoma, with higher ORR and median overall survival than patients underwent percutaneous nephrostomy without seed strand.
Patterns of global burden of 13 diseases attributable to lead exposure, 1990–2019
Authors: Xu Tongtong , Lin Kangqian , Cao Miao , Miao Xinlu , Guo Heng , Rui Dongsheng , Hu Yunhua , Yan Yizhong
Published: June 2023

Objectives

Understanding the spatio-temporal patterns of the global burden of various diseases resulting from lead exposure is critical for controlling lead pollution and disease prevention.

Methods

Based on the 2019 Global Burden of Disease (GBD) framework and methodology, the global, regional, and national burden of 13 level-three diseases attributable to lead exposure were analyzed by disease type, patient age and sex, and year of occurrence. Population attributable fraction (PAF), deaths and disability-adjusted life years (DALYs), age-standardized mortality rate (ASMR) and age-standardized DALYs rate (ASDR) obtained from the GBD 2019 database were used as descriptive indicators, and the average annual percentage change (AAPC) was estimated by a log-linear regression model to reflect the time trend.

Results and conclusions

From 1990 to 2019, the number of deaths and DALYs resulting from lead exposure increased by 70.19% and 35.26%, respectively; however, the ASMR and ASDR decreased by 20.66% and 29.23%, respectively. Ischemic heart disease (IHD), stroke, and hypertensive heart disease (HHD) showed the highest increases in deaths; IHD, stroke, and diabetes and kidney disease (DKD) had the fastest-growing DALYs. The fastest decline in ASMR and ASDR was seen in stroke, with AAPCs of -1.25 (95% CI [95% confidence interval]: -1.36, -1.14) and -1.66 (95% CI: -1.76, -1.57), respectively. High PAFs occurred mainly in South Asia, East Asia, the Middle East, and North Africa. Age-specific PAFs of DKD resulting from lead exposure were positively correlated with age, whereas the opposite was true for mental disorders (MD), with the burden of lead-induced MD concentrated in children aged 0–6 years. The AAPCs of ASMR and ASDR showed a strong negative correlation with the socio-demographic index. Our findings showed that the global impact of lead exposure and its burden increased from 1990 to 2019 and varied significantly according to age, sex, region, and resulting disease. Effective public health measures and policies should be adopted to prevent and control lead exposure.
Soft tissue dimensional change using customized titanium healing abutment in immediate implant placement in posterior teeth
Authors: Lertwongpaisan Tanporn , Amornsettachai Parinya , Panyayong Woraphong , Suphangul Suphachai
Published: June 2023

Background

The morphologic and dimensional alveolar bone is significant for resorption in the first 3 months after tooth removal because they restrict treatment outcomes with respect to function and esthetic. Following teeth extraction, the width and height of the alveolar ridge contour are reduced in both the horizontal and vertical dimensions. Following implant placement, the gingival morphology should be changed minimally compared to pre-extraction. Surrounding natural-like tissue is also an ultimate goal of the dental implant treatment, which is correlated with the cervical third contour on the anatomical tooth, for comfortable cleansing, food impaction avoidance, and esthetics.

Purpose

To evaluate the peri-implant soft tissue changes after immediate implant placement (IIP) with the use of a customized titanium healing abutment in the posterior teeth.

Method

Digital impressions using the intraoral scanner (MEDIT i500) were taken from 30 patients. Customized titanium healing abutments were designed and milled before extraction. Flapless extractions were done using surgical guides, 32 immediate implants placement were done in posterior areas, and healing abutments were placed. Soft tissues were scanned during pre-operation, and post-surgery during the 1st, 3rd, and 6th months. A 3D analysis program (Final Surface) evaluated the gingival margin distance, height, contour width, and volume in each period. SPSS was used to analyze the data with a p-value = 0.05. The between-time interval comparisons were done and the analysis was done using a Multivariate test.

Results

Customized titanium healing abutments used in immediate implantation maintained optimal peri-implant mucosa. In intermittent periods, there was no significant reduction in all aspects of the margin distances and heights. During the entire period, the margin height reduction on the buccal, lingual, mesial, and distal was 0.63 mm, 0.93 mm, 0.08 mm, and 0.24 mm, respectively, and contour width reduction on the buccal, lingual, and buccolingual was 0.59 mm, 0.43 mm, and 1.03 mm, respectively. There was a significant reduction in the total buccolingual contour width in the 1st month and total volume in the 3rd to 6th months.

Conclusions

Immediate implant placement with customized titanium healing abutment can achieve the optimal peri-implant mucosa and this protocol is an alternative for soft tissue management.
Systematic review and network meta-analysis of the accuracy of the orthodontic mini-implants placed in the inter-radicular space by image-guided-based techniques
Authors: Mihit Mihit Fatima Zahrae , Zubizarreta-Macho Álvaro , Montiel-Company José María , Albaladejo Martínez Alberto
Published: June 2023

Objective

The aim of the present systematic review and network meta-analysis (NMA) is to analyze the accuracy of image-guided-based orthodontic mini-implants placement techniques in the inter-radicular space.

Methods

The study was conducted under the PRISMA recommendations. Three databases were searched up to July 2022. In vitro randomized experimental trials (RETs) including static computer-aided implant surgery (s-CAIS), mixed reality (MR), soft tissue static computer-aided implant surgery (ST s-CAIS) and conventional free-hand technique (FHT) for the orthodontic mini-implants placement in the inter-radicular space were selected. The risk of bias was assessed using the Current Research Information System scale. A random effects model was used in the NMA. Direct comparisons were combined with a random effects model in a frequentist NMA to estimate indirect comparisons, and the estimated effect size of the comparisons between techniques were analyzed by difference of means. Inconsistency was assessed with the Q test, with a significance level of p < 0.05, and a net heat plot.

Results

A total of 92 articles was identified, and 8 RETs (8 direct comparisons of 4 techniques) were included in the NMA, which examined 4 orthodontic mini-implants placement techniques: s-CAIS, MR, ST s-CAIS, and FHT. Taking FHT as reference, s-CAIS and ST s-CAIS showed statistically significant coronal and apical deviation. In addition, s-CAIS showed statistically significant angular deviation. However, MR did not show statistically significant differences with respect to FHT, which presented the highest p-score. At the coronal deviation, ST s-CAIS presented the highest P-score (0.862), followed by s-CAIS (0.721). At the apical deviation, s-CAIS presented the highest P-score (0.844), followed by ST s-CAIS (0.791). Finally, at the angular deviation s-CAIS presented again the highest P-score (0.851).

Conclusions

Within the limitations of this study, it was found that the image-guided-based orthodontic mini-implants placement techniques showed more accuracy than the free-hand conventional placement technique; specially the computer-aided static navigation techniques for the orthodontic mini-implants placed in the inter-radicular space.
Tutorless board game as an alternative to tabletop exercise for disaster response training: perception of interaction engagement and behavioral intention
Authors: Chew Keng Sheng , Wong Shirly Siew-Ling , Tarazi Izzah Safiah binti , Koh Janet Weilly , Ridzuan Nor Azeriyatul ‘Ain binti , Wan Allam Syed Azrai Shah bin
Published: June 2023

Background

Although tabletop exercise is a commonly used method for disaster response training, it is labor-intensive, requires a tutor for facilitation and may not be ideal in a pandemic situation. Board game is a low-cost and portable alternative that can be utilized for this purpose. The purpose of this study was to compare the perception of interaction engagement and behavioral intention to use a newly developed board game with tabletop exercise for disaster training.

Methods

Using the Mechanics-Dynamics-Aesthetics’ (MDA) framework, a new, tutorless educational board game known as the Simulated Disaster Management And Response Triage training (“SMARTriage”) was first developed for disaster response training. Subsequently, the perceptions of 113 final year medical students on the “SMARTriage” board game was compared with that of tabletop exercise using a crossover design.

Results

Using Wilcoxon signed rank test, it was that found that tabletop exercise was generally rated significantly higher (with p < 0.05) in terms of perceived usefulness, perceived ease of use and behavioral intention compared to tutorless “SMARTriage” board game. However, in terms of attitude and interaction engagement, there was no significant difference between these two learning methods for most of the items.

Conclusion

Although a clear preference for tutorless board game was not demonstrated, this study suggests that board game was not inferior to tabletop exercise in fostering interaction engagement suggesting that “SMARTriage” board game could potentially be used as an adjunct for teaching and learning activities.
Nursing interventions in preventing pressure injuries in acute inpatient care: a cross-sectional national study
Authors: Tervo-Heikkinen Tarja , Heikkilä Anniina , Koivunen Marita , Kortteisto Tiina , Peltokoski Jaana , Salmela Susanne , Sankelo Merja , Ylitörmänen Tuija , Junttila Kristiina
Published: June 2023

Background

Several nursing interventions for pressure injury prevention have been identified, including risk and skin status assessment. The aim of this study was to explore prevention of pressure injuries in Finnish acute inpatient care. The data were collected on pressure injury risk and skin status assessments, repositioning, the use of support surfaces, preventive skin care, malnutrition risk assessment, and nutritional care.

Methods

This multicentre, cross-sectional study was conducted in 16 acute care hospitals, excluding psychiatric care. Adult patients from inpatient care were recruited on the annual international Stop Pressure Ulcers Day in 2018 and 2019. Enrolment covered 6,160 participants in 503 units. Descriptive statistics were used to describe pressure injuries, risk assessments, and preventive nursing interventions. Cross tabulation, Pearson’s chi-square and Fisher’s exact tests were also used. Reporting follows the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines.

Results

In all, 30% of the participants had their pressure injury risk assessed during the care, and for 19% within 8 h after admission. The same time limit in risk assessment was fulfilled for 16% of the participants with a pressure injury, and 22% of the participants using a wheelchair or being bedridden. A skin status assessment within 8 h after admission was conducted for 30% of all participants, and for 29% of the participants with a pre-existing pressure injury, and for 38% of the participants using a wheelchair or being bedridden. The risk of malnutrition was screened in 20% of the participants. Preventive interventions were targeted to participants with a pressure injury instead of patients with a high-pressure injury risk.

Conclusion

This study adds evidence about pressure injury risk assessments and the implementation of preventive nursing interventions in Finnish acute care. Skin status and pressure injury risk assessments were irregularly conducted, and the outcome was not used by nurses to guide the implementation of preventive interventions. The results reveal the gaps in evidence-based nursing practice, which require further efforts to prevent pressure injuries. Improving the national focus on pressure injury prevention practice is critical for improving healthcare for our patients.
Krüppel-like factor 10 modulates stem cell phenotypes of pancreatic adenocarcinoma by transcriptionally regulating notch receptors
Authors: Tsai Yi-Chih , Cheng Kung Hung , Jiang Shih Sheng , Hawse John R. , Chuang Shun En , Chen Su Liang , Huang Tze-Sing , Ch’ang Hui-Ju
Published: June 2023

Background

Pancreatic adenocarcinoma (PDAC) is well known for its rapid distant metastasis and local destructive behavior. Loss of Krüppel-like factor 10 (KLF10) contributes to distant migration of PDAC. The role of KLF10 in modulating tumorigenesis and stem cell phenotypes of PDAC is unclear.

Methods

Additional depletion of KLF10 in KC (LSL: KrasG12D; Pdx1-Cre) mice, a spontaneous murine PDAC model, was established to evaluate tumorigenesis. Tumor specimens of PDAC patients were immune-stained of KLF10 to correlate with local recurrence after curative resection. Conditional overexpressing KLF10 in MiaPaCa and stably depleting KLF10 in Panc-1 (Panc-1-pLKO-shKLF10) cells were established for evaluating sphere formation, stem cell markers expression and tumor growth. The signal pathways modulated by KLF10 for PDAC stem cell phenotypes were disclosed by microarray analysis and validated by western blot, qRT-PCR, luciferase reporter assay. Candidate targets to reverse PDAC tumor growth were demonstrated in murine model.

Results

KLF10, deficient in two-thirds of 105 patients with resected pancreatic PDAC, was associated with rapid local recurrence and large tumor size. Additional KLF10 depletion in KC mice accelerated progression from pancreatic intraepithelial neoplasia to PDAC. Increased sphere formation, expression of stem cell markers, and tumor growth were observed in Panc-1-pLKO-shKLF10 compared with vector control. Genetically or pharmacologically overexpression of KLF10 reversed the stem cell phenotypes induced by KLF10 depletion. Ingenuity pathway analysis and gene set enrichment analysis showed that Notch signaling molecules, including Notch receptors 3 and 4, were over-expressed in Panc-1-pLKO-shKLF10. KLF10 transcriptionally suppressed Notch-3 and -4 by competing with E74-like ETS transcription factor 3, a positive regulator, for promoter binding. Downregulation of Notch signaling, either genetically or pharmacologically, ameliorated the stem cell phenotypes of Panc-1-pLKO-shKLF10. The combination of metformin, which upregulated KLF10 expression via phosphorylating AMPK, and evodiamine, a non-toxic Notch-3 methylation stimulator, delayed tumor growth of PDAC with KLF10 deficiency in mice without prominent toxicity.

Conclusions

These results demonstrated a novel signaling pathway by which KLF10 modulates stem cell phenotypes in PDAC through transcriptionally regulating Notch signaling pathway. The elevation of KLF10 and suppression of Notch signaling may jointly reduce PDAC tumorigenesis and malignant progression.
Establishment of CRISPR-Cas9 system in Bifidobacteria animalis AR668
Authors: Li Jiao , Song Xin , Xiong Zhiqiang , Wang Guangqiang , Xia Yongjun , Yang Yijin , Ai Lianzhong
Published: June 2023

Bifidobacteria are representative intestinal probiotics that have extremely high application value in the food and medical fields. However, the lack of molecular biology tools limits the research on functional genes and mechanisms of bifidobacteria. The application of an accurate and efficient CRISPR system to genome engineering can fill the gap in efficient genetic tools for bifidobacteria. In this study, CRISPR system of B. animalis AR668 was established, which successfully knocked out gene 0348 and gene 0208. The influence of different homology arms and fragments on the knockout effect of the system was explored. In addition, the inducible plasmid curing system of bifidobacteria was innovatively established. This study contributes to the genetic modification and functional mechanism analysis of bifidobacteria.
Exosomal miR-125b-5p derived from adipose-derived mesenchymal stem cells enhance diabetic hindlimb ischemia repair via targeting alkaline ceramidase 2
Authors: Guo Jiahe , Yang Xiaofan , Chen Jing , Wang Cheng , Sun Yue , Yan Chengqi , Ren Sen , Xiong Hewei , Xiang Kaituo , Zhang Maojie , Li Chengcheng , Jiang Guoyong , Xiang Xuejiao , Wan Gui , Jiang Tao , Kang Yu , Xu Xiang , Chen Zhenbing , Li Wenqing
Published: June 2023

Introduction

Ischemic diseases caused by diabetes continue to pose a major health challenge and effective treatments are in high demand. Mesenchymal stem cells (MSCs) derived exosomes have aroused broad attention as a cell-free treatment for ischemic diseases. However, the efficacy of exosomes from adipose-derived mesenchymal stem cells (ADSC-Exos) in treating diabetic lower limb ischemic injury remains unclear.

Methods

Exosomes were isolated from ADSCs culture supernatants by differential ultracentrifugation and their effect on C2C12 cells and HUVECs was assessed by EdU, Transwell, and in vitro tube formation assays separately. The recovery of limb function after ADSC-Exos treatment was evaluated by Laser-Doppler perfusion imaging, limb function score, and histological analysis. Subsequently, miRNA sequencing and rescue experiments were performed to figure out the responsible miRNA for the protective role of ADSC-Exos on diabetic hindlimb ischemic injury. Finally, the direct target of miRNA in C2C12 cells was confirmed by bioinformatic analysis and dual-luciferase report gene assay.

Results

ADSC-Exos have the potential to promote proliferation and migration of C2C12 cells and to promote HUVECs angiogenesis. In vivo experiments have shown that ADSC-Exos can protect ischemic skeletal muscle, promote the repair of muscle injury, and accelerate vascular regeneration. Combined with bioinformatics analysis, miR-125b-5p may be a key molecule in this process. Transfer of miR-125b-5p into C2C12 cells was able to promote cell proliferation and migration by suppressing ACER2 overexpression.

Conclusion

The findings revealed that miR-125b-5p derived from ADSC-Exos may play a critical role in ischemic muscle reparation by targeting ACER2. In conclusion, our study may provide new insights into the potential of ADSC-Exos as a treatment option for diabetic lower limb ischemia.
Safety outcomes in patients with rheumatoid arthritis treated with abatacept: results from a multinational surveillance study across seven European registries
Authors: Dominique Alyssa , Hetland Merete Lund , Finckh Axel , Gottenberg Jacques-Eric , Iannone Florenzo , Caporali Roberto , Kou Tzuyung Douglas , Nordstrom Dan , Hernandez Maria Victoria , Sánchez-Piedra Carlos , Sánchez-Alonso Fernando , Pavelka Karel , Bond T. Christopher , Simon Teresa A.
Published: June 2023

Background

Patients with rheumatoid arthritis (RA) have an increased risk of infection and malignancy compared with the general population. Infection risk is increased further with the use of disease-modifying antirheumatic drugs (DMARDs), whereas evidence on whether the use of biologic DMARDs increases cancer risk remains equivocal. This single-arm, post-marketing study estimated the incidence of prespecified infection and malignancy outcomes in patients with RA treated with intravenous or subcutaneous abatacept.

Methods

Data were included from seven European RA quality registries: ATTRA (Anti-TNF Therapy in Rheumatoid Arthritis [Czech Republic]), DANBIO (Danish Rheumatologic Database), ROB-FIN (National Registry of Antirheumatic and Biological Treatment in Finland), ORA (Orencia and Rheumatoid Arthritis [France]), GISEA (Italian Group for the Study of Early Arthritis), BIOBADASER (Spanish Register of Adverse Events of Biological Therapies in Rheumatic Diseases), and the SCQM (Swiss Clinical Quality Management) system. Each registry is unique with respect to design, data collection, definition of the study cohort, reporting, and validation of outcomes. In general, registries defined the index date as the first day of abatacept treatment and reported data for infections requiring hospitalization and overall malignancies; data for other infection and malignancy outcomes were not available for every cohort. Abatacept exposure was measured in patient-years (p-y). Incidence rates (IRs) were calculated as the number of events per 1000 p-y of follow-up with 95% confidence intervals.

Results

Over 5000 patients with RA treated with abatacept were included. Most patients (78–85%) were female, and the mean age range was 52–58 years. Baseline characteristics were largely consistent across registries. Among patients treated with abatacept, IRs for infections requiring hospitalization across the registries ranged from 4 to 100 events per 1000 p-y, while IRs for overall malignancy ranged from 3 to 19 per 1000 p-y.

Conclusions

Despite heterogeneity between registries in terms of design, data collection, and ascertainment of safety outcomes, as well as the possibility of under-reporting of adverse events in observational studies, the safety profile of abatacept reported here was largely consistent with previous findings in patients with RA treated with abatacept, with no new or increased risks of infection or malignancy.
Pharmacological inhibition of human EZH2 can influence a regenerative β-like cell capacity with in vitro insulin release in pancreatic ductal cells
Authors: Naina Marikar Safiya , Al-Hasani Keith , Khurana Ishant , Kaipananickal Harikrishnan , Okabe Jun , Maxwell Scott , El-Osta Assam
Published: June 2023

Background

Therapeutic replacement of pancreatic endocrine β-cells is key to improving hyperglycaemia caused by insulin-dependent diabetes . Whilst the pool of ductal progenitors, which give rise to the endocrine cells, are active during development, neogenesis of islets is repressed in the human adult. Recent human donor studies have demonstrated the role of EZH2 inhibition in surgically isolated exocrine cells showing reactivation of insulin expression and the influence on the H3K27me3 barrier to β-cell regeneration. However, those studies fall short on defining the cell type active in transcriptional reactivation events. This study examines the role of the regenerative capacity of human pancreatic ductal cells when stimulated with pharmacological inhibitors of the EZH2 methyltransferase.

Results

Human pancreatic ductal epithelial cells were stimulated with the EZH2 inhibitors GSK-126, EPZ6438, and triptolide using a 2- and 7-day protocol to determine their influence on the expression of core endocrine development marker NGN3, as well as β-cell markers insulin, MAFA, and PDX1. Chromatin immunoprecipitation studies show a close correspondence of pharmacological EZH2 inhibition with reduced H3K27me3 content of the core genes, NGN3, MAFA and PDX1. Consistent with the reduction of H3K27me3 by pharmacological inhibition of EZH2, we observe measurable immunofluorescence staining of insulin protein and glucose-sensitive insulin response.

Conclusion

The results of this study serve as a proof of concept for a probable source of β-cell induction from pancreatic ductal cells that are capable of influencing insulin expression. Whilst pharmacological inhibition of EZH2 can stimulate secretion of detectable insulin from ductal progenitor cells, further studies are required to address mechanism and the identity of ductal progenitor cell targets to improve likely methods designed to reduce the burden of insulin-dependent diabetes.
Buffy coat signatures of breast cancer risk in a prospective cohort study
Authors: Chung Felicia Fei-Lei , Maldonado Sandra González , Nemc Amelie , Bouaoun Liacine , Cahais Vincent , Cuenin Cyrille , Salle Aurelie , Johnson Theron , Ergüner Bekir , Laplana Marina , Datlinger Paul , Jeschke Jana , Weiderpass Elisabete , Kristensen Vessela , Delaloge Suzette , Fuks François , Risch Angela , Ghantous Akram , Plass Christoph , Bock Christoph , Kaaks Rudolf , Herceg Zdenko
Published: June 2023

Background

Epigenetic alterations are a near-universal feature of human malignancy and have been detected in malignant cells as well as in easily accessible specimens such as blood and urine. These findings offer promising applications in cancer detection, subtyping, and treatment monitoring. However, much of the current evidence is based on findings in retrospective studies and may reflect epigenetic patterns that have already been influenced by the onset of the disease.

Methods

Studying breast cancer, we established genome-scale DNA methylation profiles of prospectively collected buffy coat samples (n = 702) from a case–control study nested within the EPIC-Heidelberg cohort using reduced representation bisulphite sequencing (RRBS).

Results

We observed cancer-specific DNA methylation events in buffy coat samples. Increased DNA methylation in genomic regions associated with SURF6 and REXO1/CTB31O20.3 was linked to the length of time to diagnosis in the prospectively collected buffy coat DNA from individuals who subsequently developed breast cancer. Using machine learning methods, we piloted a DNA methylation-based classifier that predicted case–control status in a held-out validation set with 76.5% accuracy, in some cases up to 15 years before clinical diagnosis of the disease.

Conclusions

Taken together, our findings suggest a model of gradual accumulation of cancer-associated DNA methylation patterns in peripheral blood, which may be detected long before clinical manifestation of cancer. Such changes may provide useful markers for risk stratification and, ultimately, personalized cancer prevention.
A novel live attenuated duck Tembusu virus vaccine targeting N7 methyltransferase protects ducklings against pathogenic strains
Authors: Wu Xuedong , Huang Shanzhi , Wang Mingshu , Chen Shun , Liu Mafeng , Zhu Dekang , Zhao Xinxin , Wu Ying , Yang Qiao , Zhang Shaqiu , Huang Juan , Ou Xumin , Zhang Ling , Liu Yunya , Yu Yanling , Gao Qun , Mao Sai , Sun Di , Tian Bin , Yin Zhongqiong , Jing Bo , Cheng Anchun , Jia Renyong
Published: June 2023

Duck Tembusu virus (DTMUV), an emerging pathogenic flavivirus, causes markedly decreased egg production in laying duck and neurological dysfunction and death in ducklings. Vaccination is currently the most effective means for prevention and control of DTMUV. In previous study, we have found that methyltransferase (MTase) defective DTMUV is attenuated and induces a higher innate immunity. However, it is not clear whether MTase-deficient DTMUV can be used as a live attenuated vaccine (LAV). In this study, we investigated the immunogenicity and immunoprotection of N7-MTase defective recombinant DTMUV K61A, K182A and E218A in ducklings. These three mutants were highly attenuated in both virulence and proliferation in ducklings but still immunogenic. Furthermore, a single-dose immunization with K61A, K182A or E218A could induce robust T cell responses and humoral immune responses, which could protect ducks from the challenge of a lethal-dose of DTMUV-CQW1. Together, this study provides an ideal strategy to design LAVs for DTMUV by targeting N7-MTase without changing the antigen composition. This attenuated strategy targeting N7-MTase may apply to other flaviviruses.
Roles of bile acids signaling in neuromodulation under physiological and pathological conditions
Authors: Xing Chen , Huang Xin , Wang Dongxue , Yu Dengjun , Hou Shaojun , Cui Haoran , Song Lung
Published: June 2023

Bile acids (BA) are important physiological molecules not only mediating nutrients absorption and metabolism in peripheral tissues, but exerting neuromodulation effect in the central nerve system (CNS). The catabolism of cholesterol to BA occurs predominantly in the liver by the classical and alternative pathways, or in the brain initiated by the neuronal-specific enzyme CYP46A1 mediated pathway. Circulating BA could cross the blood brain barrier (BBB) and reach the CNS through passive diffusion or BA transporters. Brain BA might trigger direct signal through activating membrane and nucleus receptors or affecting activation of neurotransmitter receptors. Peripheral BA may also provide the indirect signal to the CNS via farnesoid X receptor (FXR) dependent fibroblast growth factor 15/19 (FGF15/19) pathway or takeda G protein coupled receptor 5 (TGR5) dependent glucagon-like peptide-1 (GLP-1) pathway. Under pathological conditions, alterations in BA metabolites have been discovered as potential pathogenic contributors in multiple neurological disorders. Attractively, hydrophilic ursodeoxycholic acid (UDCA), especially tauroursodeoxycholic acid (TUDCA) can exert neuroprotective roles by attenuating neuroinflammation, apoptosis, oxidative or endoplasmic reticulum stress, which provides promising therapeutic effects for treatment of neurological diseases. This review summarizes recent findings highlighting the metabolism, crosstalk between brain and periphery, and neurological functions of BA to elucidate the important role of BA signaling in the brain under both physiological and pathological conditions.
Two steps forward, one step back? Party competition, cooperative federalism, and transport policy reforms in Germany
Authors: Souris Antonios , Stecker Christian , Jungjohann Arne
Published: June 2023

Background

Transport policy has regained political relevance in Germany. The successful realization of the Verkehrswende,—the extensive transition toward sustainable transport and mobility—is central to reaching climate neutrality. In 2020, the Federal Government proposed the reform of two key ordinances that have regulated road traffic so far. The amendment was aimed at implementing several provisions at the expense of car drivers and, at the same time, in favor of cyclists and pedestrians. Due to cooperative federalism, the governments of the 16 constituent units (Länder) had to adopt the amendment in the Bundesrat, Germany’s second chamber. In the legislative process, however, the reform ultimately failed in its original scope. Using it as a particularly instructive case study, we show how and why party competition and cooperative federalism hamper comprehensive transport policy reforms in Germany.

Results

In the German political system, political interests interact within a complex web of cooperative federalism. To understand partisan encroachment on the federal decision-making processes, this paper uses a process-tracing approach. To investigate decision-making in the Bundesrat and its outcomes, the empirical analysis combines qualitative analyses of several publicly available sources. We can empirically demonstrate that political parties influenced legislative procedures. The reform failed in its original scope because the three political parties with veto power in the Bundesrat insisted on their positions and were not willing to agree on a compromise.

Conclusions

For the implementation of the Verkehrswende, the German federal system proves to be both a blessing and a curse. On one hand, the institutional design of the Bundesrat constrains extreme positions and helps promote decisions most citizens may agree with. The Länder governments and administrations can also contribute their expertise and local experience to federal legislation via the Bundesrat. On the other hand, veto powers are ubiquitous in the German system of cooperative federalism. Therefore, it is prone to blockades. The actions of the political parties in the Bundesrat have hampered the comprehensive reform of road traffic regulations that was originally envisaged. Policymaking took two steps forward toward implementing the Verkehrswende, only to immediately take one step back again.
Photodistributed Stevens–Johnson syndrome and toxic epidermal necrolysis: a systematic review and proposal for a new diagnostic classification
Authors: McKinley Blake Jeffrey , Allen Mitchell Edger , Michels Nicole
Published: June 2023

Background

Ultraviolet radiation (UVR) exposure is commonly reported as a risk factor for Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). However, minimal evaluation of photo-induced SJS/TEN has been conducted. Thus, this review identifies all cases of SJS/TEN that are linked to an acute exposure of UVR and outlines the unifying characteristics of these cases. Furthermore, the theoretical pathogenesis, differential diagnoses, and proposed diagnostic criteria are defined.

Methods

PubMed, Google Scholar, and other databases and websites were searched from inception to September 2021 to identify studies that met inclusion criteria. The following keywords were utilized: “Stevens-Johnson syndrome” and “toxic epidermal necrolysis” with “ultraviolet,” “photodistributed,” “photo-induced,” “photosensitivity,” and “photo.” One reviewer assessed study characteristics, with confirmation by a second. The risk of bias was assessed independently by another.

Results

Thirteen patient cases were identified, all reporting ultraviolet radiation prior to rash onset and an underlying causal drug. Case classifications included 7/13 SJS and 6/13 TEN. All cases described the rash as photodistributed with UVR exposure prior to rash onset (delay of 1–3 days) and a causal drug. 10 cases provided evidence that the photodistributed rash lacked linear demarcation (as in a sunburn) with satellite target-like lesions. No cases described a flu-like prodrome.

Discussion

Mucositis, palmar and plantar rash, a positive Nikolsky sign, and a prolonged disease course can help distinguish from photosensitive reactions, while a negative direct immunofluorescence test is important to distinguish from other photo-induced disorders.

Conclusion

Physicians should be aware that UVR may precipitate SJS/TEN in patients taking susceptible drugs. After a 24-h delay from UVR exposure, a non-distinct, photodistributed rash appears with no flu-like prodrome and progresses for at least 48 h to include vesiculobullous eruptions and mucous membrane involvement. Photodistributed SJS/TEN appears to be photo-drug-induced with a unique onset and rash presentation that should be recognized as a distinct diagnosis.
Comparison of the lower limit of normal to the fixed ratio method for the diagnosis of airflow obstruction at high altitudes: a large cross-sectional survey of subjects living between 3000–4700 m above sea level
Authors: Huang Yilin , Xing Zhenzhen , Janssens Jean-Paul , Chai Di , Liu Weiming , Wang Yuxia , Ma Yali , Tong Yaqi , Guo Yanfei
Published: June 2023

Background

There is no general agreement on the preferential use of a fixed ratio (FR) of forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) < 0.7 vs. the lower limit of normal (LLN) of FEV1/FVC to define airflow obstruction. Determining the impact of these different cut-off levels in people living at high altitudes has not been studied. We assessed the prevalence of airflow obstruction and its clinical characteristics in residents living at high altitude using a fixed ratio and the LLN of FEV1/FVC according to Global Lung Initiative 2012 (GLI) reference values.

Methods

Using a multistage stratified sampling method, 3702 participants (aged ≥ 15 years) living at an altitude of 3000–4700 m in Tibet were included.

Results

11.4% and 7.7% of participants had airflow obstruction according to GLI-LLN and a fixed FEV1/FVC cut-off value, respectively. The participants in the FR−/LLN+ group were younger, predominantly female, more frequently exposed to household air pollution, and had a higher proportion of chronic obstructive pulmonary disease assessment test scores ≥ 10 than those in the FR−/LLN− group. They also had a significantly lower FEV1 and a higher frequency of small airway dysfunction. Compared with the participants of the FR+/LLN+ group, those in the FR−/LLN+ group showed no significant difference in the risk factors for airflow obstruction and respiratory symptoms, but had a lower prevalence of small airway dysfunction.

Conclusions

Defining airflow obstruction according to LLN, instead of using an FR, identified younger individuals with more frequent clinical symptoms of airflow obstruction and small airway dysfunction.
Dentofacial effects of miniscrew-anchored maxillary protraction on prepubertal children with maxillary deficiency: a randomized controlled trial
Authors: Kamel Ahmed Mohamed , Tarraf Nour Eldin , Fouda Ahmed Maher , Hafez Ahmad Mohammed , El-Bialy Ahmed , Wilmes Benedict
Published: June 2023

Background

The introduction of bone-anchored maxillary protraction eliminated the side effects of facemask in the early treatment of patients with maxillary retrusion. This study aimed to evaluate the effects of miniscrew-anchored maxillary protraction (MAMP) and compare them with the growth changes in an untreated control group in growing patients with Class III malocclusion.

Methods

Forty growing patients with Class III malocclusion and retrognathic maxilla were randomly allocated into two groups: treated and control groups. In the treated group, patients were treated with full-time intermaxillary Class III elastics (C3E) anchored by a hybrid hyrax (HH) in the maxilla and a bone-supported bar in the mandible. Protraction was stopped after obtaining a positive overjet. Cephalometric radiographs were acquired before and after the treatment. Data were statistically analyzed on an intention-to-treat basis. Intergroup comparisons were also made using analysis of covariance with the readings at T0 as a covariate.

Results

Forty patients agreed to participate, and 30 of them completed the study (treated group, n = 17; control group, n = 13). The average treatment duration was 11.9 months. MAMP resulted in a significant maxillary advancement (A-VR, 4.34 mm) with significant control over the mandibular growth. No significant increase in the mandibular plane angle was found in the treated group compared with the control group. The upper and lower incisors showed significant protrusion in the treated group.

Conclusions

Within the limitations of this study and high attrition rate, the MAMP protocol can effectively increase maxillary forward growth with good control over the growth of the mandible antero-posteriorly and vertically.
Effects of bagasse biochar application on soil organic carbon fixation in manganese-contaminated sugarcane fields
Authors: Hu Lening , Yang Yu , Liu Xue Hui , Li SHuangli , Li Ke , Deng Hua
Published: June 2023

Background

In recent years, there have been several studies on the remediation of heavy metal pollution in soil by the application of biochar. However, little attention has been paid to understanding the effects and underlying mechanisms of biochar on soil carbon sequestration in manganese-contaminated farmlands. Therefore, in this study, bagasse biochar was applied to the soil in different proportions (0%, 0.5%, 2%, and 5%) and the test was conducted indoors for 100 days at a constant temperature. Soil physical and chemical properties, organic carbon mineralization, organic carbon components, and enzyme activities were analyzed in this study.

Results

In this study, when compared with the control, the application of 0.5%, 2%, and 5% bagasse biochar to the manganese-contaminated sugarcane field soil effectively reduced the cumulative CO2 emissions, i.e., decreased by 123.18 mg·kg−1, 208.28 mg·kg−1, and 287.79 mg·kg−1, respectively. Among the different treatment groups, the highest decrease in cumulative CO2 emissions was observed in the 5% bagasse biochar-treated soil when compared with the control. The application of bagasse biochar increased the soil microbial biomass carbon content by 12.72 mg·kg−1, 13.71 mg·kg−1, and 15.10 mg·kg−1, respectively when compared with the control. The soil nutrients and enzyme activities significantly increased with the increase in biochar application amount.

Conclusions

The application of bagasse biochar to manganese-contaminated sugarcane soil field effectively inhibited the mineralization of soil organic carbon, improved the carbon sequestration potential of manganese-contaminated sugarcane field soil, and provided a theoretical basis for the carbon sequestration mechanism in manganese-contaminated farmland soil.

Graphical Abstract
Recent progress of eco-friendly manufacturing process of efficient perovskite solar cells
Authors: Kwon Nayoon , Lee Jaehee , Ko Min Jae , Kim Young Yun , Seo Jangwon
Published: June 2023

Perovskite solar cells (PSCs) have the potential to produce solar energy at a low cost, with flexibility, and high power conversion efficiency (PCE). However, there are still challenges to be addressed before mass production of PSCs, such as prevention from degradation under external stresses and the uniform, large-area formation of all layers. Among them, the most challenging aspect of mass production of PSCs is creating a high-quality perovskite layer using environmentally sustainable processes that are compatible with industry standards. In this review, we briefly introduce the recent progresses upon eco-friendly perovskite solutions/antisolvents and film formation processes. The eco-friendly production methods are categorized into two: (1) employing environmentally friendly solvents for perovskite precursor ink/solution, and (2) replacing harmful, volatile antisolvents or even limiting their use during the perovskite film formation process. General considerations and criteria for each category are provided, and detailed examples are presented, specifically focused on the works have done since 2021. In addition, the importance of controlling the crystallization behavior of the perovskite layer is highlighted to develop antisolvent-free perovskite formation methods.

Graphical Abstract
Incidence and risk factors of cardiovascular disease among population aged 40–70 years: a population-based cohort study in the South of Iran
Authors: Rezaianzadeh Abbas , Moftakhar Leila , Seif Mozhgan , Johari Masoumeh Ghoddusi , Hosseini Seyed Vahid , Dehghani Seyed Sina
Published: June 2023

Background

Cardiovascular diseases are the main cause of mortality in the world. This study aimed to estimate the incidence and identify the risk factors of these diseases.

Methods

This prospective cohort study was performed on 9442 individuals aged 40–70 years in Kharameh, a city in the South of Iran, in 2015–2022. The subjects were followed up for 4 years. The demographic information, behavioral habits, biological parameters, and history of some diseases were examined. The density incidence of cardiovascular disease was calculated. The log-rank test was calculated to assess the cardiovascular incidence difference between men and women. Simple and multiple Cox regression with Firth's bias reduction method were used to identify the predictors of cardiovascular disease.

Results

The mean ± SD age of the participants was 51.4 ± 8.04 years, and the density incidence was estimated at 1.9 cases per 100,000 person-day. The log-rank test showed that men had a higher risk of cardiovascular disease than women. The Fisher's exact test showed a statistically significant difference between the incidence of cardiovascular diseases in different age groups, education levels, diabetes, and hypertension in men and women. The results of multiple Cox regression revealed that with increasing age, the risk of developing CVDs increased. In addition, the risk of cardiovascular disease is higher in people with kidney disease (HRadj = 3.4, 95% CI 1.3 to 8.7), men (HRadj = 2.3, 95% CI 1.7 to 3.2), individuals with hypertension (HRadj = 1.6, 95% CI 1.3 to 2.1), diabetics (HRadj = 2.3, 95%c CI 1.8 to 2.9), and alcohol consumption (HRadj = 1.5, 95% CI 1.09 to 2.2).

Conclusions

In the present study, diabetes, hypertension, age, male gender, and alcohol consumption were identified as the risk factors for cardiovascular diseases; three variables of diabetes, hypertension and alcohol consumption were among the modifiable risk factors, so if they were removed, the incidence of cardiovascular disease could greatly reduce. Therefore, it is necessary to develop strategies for appropriate interventions to remove these risk factors.