bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel compound heterozygous BEST1 gene mutation in two siblings causing autosomal recessive bestrophinopathy
Authors: Haque Obaid Imtiyazul , Chandrasekaran Anbukayalvizhi , Nabi Faisal , Ahmad Owais , Marques João Pedro , Ahmad Tanweer
Published: December 2022

Purpose

To describe the clinical features, imaging characteristics, and genetic test results associated with a novel compound heterozygous mutation of the BEST1 gene in two siblings with autosomal recessive bestrophinopathy.

Methods

Two siblings underwent a complete ophthalmic examination, including dilated fundus examination, fundus photography, fundus autofluorescence imaging, spectral-domain optical coherence tomography, fluorescein angiography, electroretinography, and electrooculography. A clinical diagnosis of autosomal recessive bestrophinopathy was established based on ocular examination and multimodal retinal imaging. Subsequently, clinical exome sequencing consisting of a panel of 6670 genes was carried out to confirm the diagnosis and assess genetic alterations in the protein-coding region of the genome of the patients. The identified mutations were tested in the two affected siblings and one of their parents.

Results

Two siblings (a 17-year-old female and a 15-year-old male) presented with reduced visual acuity and bilaterally symmetrical subretinal deposits of hyperautofluorescent materials in the posterior pole, which showed staining in the late phase of fluorescein angiogram. Spectral-domain optical coherence tomography demonstrated hyperreflective subretinal deposits and subretinal fluid accumulation. Both patients shared two mutations in the protein-coding region of the BEST1 gene, c.103G > A, p.(Glu35Lys) and c.313C > A, p.(Arg105Ser) (a novel disease-causing mutation). Sanger sequencing confirmed that the unaffected mother of the proband was carrying p.(Glu35Lys) variant in a heterozygous state.

Conclusions

We have identified and described the phenotype of a novel disease-causing mutation NM_004183.4:c.313C > A, p.(Arg105Ser) in a heterozygous state along with a previously reported mutation NM_004183.4:c.103G > A, p.(Glu35Lys) of the BEST1 gene in two related patients with autosomal recessive bestrophinopathy.
The choice of message and messenger to drive behavior change that averts the health impacts of wildfires: an online randomized controlled experiment
Authors: Aminpour Payam , Helgeson Jennifer F. , Ferraro Paul J.
Published: December 2022

Background

To reduce the negative health effects from wildfire smoke exposure, effective risk and health communication strategies are vital. We estimated the behavioral effects from changes in message framing and messenger in public health messages about wildfire smoke on Facebook.

Methods

During September and October 2021, we conducted a preregistered online randomized controlled experiment in Facebook. Adult Facebook users (n = 1,838,100), living in nine wildfire-prone Western U.S. states, were randomly assigned to see one of two ad versions (narrative frame vs. informational frame) from one of two messengers (government vs. academic). We estimated the effects of narrative framing, the messenger, and their interactions on ad click-through rates, a measure of recipient information-seeking behavior.

Results

Narrative frame increased click-through rates by 25.3% (95% CI = 22.2, 28.4%), with larger estimated effects among males, recipients in areas with less frequent exposure to heavy wildfire smoke, and in areas where predominant political party affiliation of registered voters was Republican (although not statistically different from predominantly-Democrat areas). The estimated effect from an academic messenger compared to a government messenger was small and statistically nonsignificant (2.2%; 95% CI = − 0.3, 4.7%). The estimated interaction effect between the narrative framing and the academic messenger was also small and statistically nonsignificant (3.9%; 95% CI = − 1.1, 9.1%).

Conclusions

Traditional public service announcements rely heavily on communicating facts (informational framing). Shifting from a fact-focused, informational framing to a story-focused, narrative framing could lead to more effective health communication in areas at risk of wildfires and in public health contexts more broadly.

Trial registration

Date registered: August 19, 2021; Registration DOI: https://doi.org/10.17605/OSF.IO/JMWUF
The use of condoms and other birth control methods among sexually active school-going adolescents in nine sub-Saharan African countries
Authors: James Peter Bai , Osborne Augustus , Babawo Lawrence Sao , Bah Abdulai Jawo , Margao Emmanuel Kamanda
Published: December 2022

Background

Adolescents in sub-Saharan Africa still face sexual and reproductive health challenges. Contraceptives have been used to address these challenges. Despite efforts at national and global levels, contraceptive uptake among young people in Africa remains a challenge due to personal, societal, and health systems-based barriers. We estimated the prevalence and correlates of condom use and other birth control methods among sexually active school-going adolescents in nine sub-Saharan African (SSA) countries.

Methods

We conducted a secondary analysis of the Global School-based Student Health Surveys (GSHS) datasets pooled from nine SSA countries. We included a sample of 27,504 school-going adolescents 11 years and younger and 18 years and older. We employed meta-analysis using a random-effects model to estimate the total prevalence of the use of condoms, other birth control methods other than a condom and any birth control method at last sexual intercourse. We conducted complex sample descriptive and logistic regression analyses to determine the characteristics and determinants of not using condoms and other birth control methods among sexually active school-going adolescents in nine sub-Saharan African countries, respectively.

Results

More than half [n = 4430, 53.8% (43.9–63.8)], two-fifth [n = 3242, 39.5% (33.2–45.9) and two-thirds of adolescents [n = 4838, 65.6% (57.5–73.7)] of sexually active in school adolescents across the nine sub-Saharan African countries used condom, other birth control methods and any form birth control method during their last sexual intercourse, respectively. The non-use of condoms at last sex was associated with being younger (less than 16 years) [AOR = 1.48;95%CI: 1.12–1.94], early sexual debut [AOR = 1.81(1.47–2.22)], having two or more sexual partners [AOR = 1.30(1.06–1.58)] and no/minimal parental support [AOR = 1.54(1.17–2.03)]. The non-use of other birth control methods at last sex was associated with being male [AOR = 1.37 (1.09–1.73)], early sexual debut [AOR = 1.83(1.48–2.27) and having no parental support [AOR = 1.64(1.34–2.00)].

Conclusion

Contraceptive need among sexually active school adolescents in the nine sub-Saharan African countries is high. Such a need calls for the development of country-specific and or the review of existing school-based sexual health education and youth-friendly sexual and reproductive health interventions that target risky adolescents and promote adolescent-parent effective communication, connectedness and support.
Minimum dietary diversity and associated factors among children under the age of five attending public health facilities in Wolaita Soddo town, Southern Ethiopia, 2021: a cross-sectional study
Authors: Moga Lencha Fikre , Jebero Zaza Zenebe , Ena Digesa Lankamo , Mulatu Ayana Tegegn
Published: December 2022

Background

Poor quality diets are the greatest obstacles to survival, growth, development, and learning in children. Dietary diversity is a major problem in developing countries including Ethiopia. For better feeding practices and focused interventions, it is essential to identify dietary diversity in children. In order to draw firm conclusions, previous studies in Ethiopia were unable to get a thorough picture of the dietary diversity among children under the age of five. Therefore, the purpose of this study was to identify minimum dietary diversity and associated factors among children under the age of five attending public health facilities in Wolaita Soddo town, Southern Ethiopia.

Methods

An institution-based cross-sectional study design was used from February to March, 2021. The sample size of the study was 406. A simple random sampling was used to select the study participants. The minimum dietary diversity of the children was assessed by a standardized dietary assessment tool. The information was gathered using a standardized questionnaire that was administered by an interviewer. The collected data were entered into Epi Data 4.6 then exported to SPSS 26 for analysis. A multivariable logistic regression model was used to identify the independent predictors of the study. The statistical significance level was set at P < 0.05, and the degree of the association was measured using an AOR with a 95% CI.

Results

A total of 399 participants were involved in this study. Nearly half (52.1%) of the study children met the minimum dietary diversity. The most popular foods were grains, roots, and tubers (79.2%), followed by dairy products (58.1%), vitamin A-rich fruits and vegetables, and grains, roots, and tubers (58.1%). Children whose mothers worked as daily workers had a lower likelihood of meeting the minimal dietary diversity requirement. However, children with separate eating plates from adults, households with food security, low monthly food expenditure, collaborative decision-making on household spending, birth intervals greater than 24 months, and health education on infant and young child feeding were more likely to achieve the minimal dietary diversity requirements.

Conclusion

The proportion of the minimum dietary diversity was higher than in previous studies from Ethiopia. The minimum dietary diversity was higher than in previous studies from Ethiopia. Family planning for birth spacing, nutritional counseling on infant and young child feeding, and parent communication in a child's feeding are critical to improve dietary diversity in a child's feeding.
Identification of serum MiRNAs as candidate biomarkers for non-small cell lung cancer diagnosis
Authors: Zhang Xintong , Tan Jinjing , Chen Yan , Ma Shang , Bai Wanqiu , Peng Yanjing , Shi Guangli
Published: December 2022

Background

Lung cancer is one of the most common solid tumors worldwide and the leading cause of cancer-associated death. Non-small cell lung cancer (NSCLC) is accounts for approximately 85% of all the lung cancers and lung squamous carcinoma (SCC) and adenocarcinoma (ADC) are the main subtypes of NSCLC. Early diagnose using serum biomarkers could improve the overall survival of patients. In this study, we aimed to identify miRNAs from serum with clinical utility in the diagnosis of NSCLC.

Methods

Ten patients with SCC, ten patients with ADC and five noncancerous individuals were enrolled in the screening cohort. miRNA expression levels in serum were measured by microarray analysis. Candidate miRNAs were validated by real-time quantitative polymerase chain reaction analysis in a validation cohort of 78 NSCLC patients and 44 noncancerous individuals. Receiver operating characteristic curves were used to assess the diagnostic performance of serum miRNAs for NSCLC. Logistic regression was used to evaluate the diagnostic value of the combination of markers.

Results

Six candidate miRNAs were differentially expressed between NSCLC patients and noncancerous individuals in the screening set (fold change > 2, p < 0.05). Among them, expression levels of miR-3149 and miR-4769.3p were confirmed to be significantly increased in tumor serum in the validation set. The area under the curve values of miR-3149 and miR-4769.3p in distinguishing NSCLC patients from noncancerous controls were 0.830 and 0.735, respectively. When combined with tumor markers CEA and Cyfra21-1, the joint diagnostic model increased the area under the curve to 0.898.

Conclusion

Serum miRNAs miR-3149 and miR-4769.3p were up-regulated in NSCLC and may be potential biomarkers for early diagnosis of lung cancer.
Three-dimensional printed customized uncemented unipolar prosthesis combined with ligament reconstruction for tumorous defect of the distal femur in children
Authors: Li Zhuangzhuang , Lu Minxun , Zhang Yuqi , You Qi , Wang Yitian , Li Longqing , Ye Qiang , Wang Yang , Luo Yi , Min Li , Zhou Yong , Tu Chongqi
Published: December 2022

Background

Hemiarthroplasty following tumor resection of the distal femur in children provides a chance to preserve the proximal tibial physis for limb elongation. Based on three-dimensional (3D) printing technology, the uncemented unipolar prosthesis with joint stability reinforced structures (JSRSs) was custom-designed for our cases. This study aimed to describe the design and assess the short-term outcomes of this refined prosthetic hemiarthroplasty.

Methods

Seven patients (four females and three males) received 3D-printed customized uncemented unipolar prosthesis for hemiarthroplasty after removal of the distal femur, from September 2019 to October 2020 at our Orthopedics department. The limb function, growth of the preserved proximal tibial physis, joint stability, and limb length discrepancy (LLD) were assessed. Complications were recorded.

Results

Six patients survived with no evidence of metastasis or local recurrence at the last follow-up, and one patient died of lung metastasis at 19 months postoperatively. Follow-up ranged from 19 to 32 months, with an average of 26 months. Elongation of the tibia was observed in all cases. At the last follow-up, four patients exhibited equal growth length compared with the healthy contralateral tibia. LLD ranged from 0.8 to 1.6 cm with a mean of 1.3 cm. The average knee range of motion was 95.3° of flexion and 4.5° of extension. All patients achieved satisfactory postoperative limb function with a mean MSTS score of 25.8. The results of the drawer, Lachman, and pivot shift tests were negative in all patients. During follow-up, painless joint space narrowing was observed in two patients. The screw for ligament fixation loosened in one of the seven patients at 17 months postoperatively. No subluxation of the joint, angular deformity, or breakage of the implant was detected in the remaining patients.

Conclusions

3D-printed customized uncemented unipolar prosthesis with JSRS would be a good choice for reconstructing tumorous defect in the distal femur in children.
Comparative retrospective study of triangular osteosynthesis with and without robotic assistance for unilateral unstable sacral fractures combined with lumbosacral junction injuries
Authors: Liu Zhao-Jie , Gu Ya , Jia Jian
Published: December 2022

Background

To compare the clinical efficacy of unilateral unstable sacral fractures (USFs) involving the lumbosacral region treated with and without robot-aided triangular osteosynthesis (TOS).

Methods

Patients of the unilateral USF combined with the ipsilateral lumbosacral junction injury (LSJI) treated with TOS were retrospectively analyzed and divided into two groups: the robot group (TOS with robotic assistance) and the conventional group (TOS with open procedure). Screw placement was assessed using the modified Gras criterion. Patients were followed up with routine visits for clinical and radiographic examinations. At the final follow-up, clinical outcomes were recorded and scored using the Majeed scoring system.

Results

Eleven patients in the robot group and seventeen patients in the conventional group were recruited into this study. Significant differences in surgical bleeding (P < 0.001) and fluoroscopy time (P = 0.002) were noted between the two groups. Operation time (P = 0.027) and fracture healing time (P = 0.041) was shorter in the robot group. There was no difference in postoperative residual displacement between the two groups (P = 0.971). According to the modified Gras criterion, the percentages of grade I for sacroiliac screws in the two groups were 90.9% (10/11) and 70.6% (12/17), and for pedicle screws were 100% (11/11) and 100% (17/17), respectively. The rate of incision-related complications was 0% (0/11) in the robot group and 11.8% (2/17) in the conventional group. Statistical differences were shown on the Majeed criterion (P = 0.039), with higher scores in the robot group.

Conclusion

TOS with robotic assistance for the treatment of unilateral USFs combined with ipsilateral LSJIs is safe and feasible, with the advantages of less radiation exposure and fewer incision-related complications.
Exploring the effects of health information seeking on e-satisfaction in online health communities: an empirical investigation
Authors: Wu Pei , Zhang Runtong
Published: December 2022

Background

Online health communities (OHCs) are becoming effective platforms for people to seek health information. Existing studies divide health information into general and specific information in OHCs. However, few studies discuss the effects of different types of information seeking in OHCs on users’ electronic satisfaction (e-satisfaction).

Objective

This study explores the effects of general and specific information seeking on users’ e-satisfaction with OHCs through the mediating roles of perceived benefits and costs drawing on the social information processing theory and the social exchange theory.

Methods

This study conducted an online survey to collected data from individuals who used OHCs to seek information. The structural equation model was used to analyze the collect data and the research model. Specifically, this study examined the common method bias and conducted a robustness check.

Results

Results show that general and specific information seeking affect e-satisfaction through the mediating roles of perceived benefits and costs. An interesting result is that general information seeking has a stronger effect on e-satisfaction than specific information seeking.

Conclusions

This study suggests that e-satisfaction should be further enhanced by information seeking as online healthcare practices evolve and change. Managers of OHCs should focus on increasing users’ perceived benefits, thereby increasing their e-satisfaction. Besides, this study discusses implications, limitations, and future research directions.
Association between competencies of biopsychosocial approach and job satisfaction of rehabilitation professionals in Ukraine
Authors: Klavina Aija , Ng Kwok , Lazarieva Olena , Mruga Marina , Tymruk-Skoropad Kateryna , Rokutov Serhii , Bazylchuk Oleh , Zakaliak Nataliia , Billiet Lorenzo , Tsizh Lubov , Popovych Dariya , Myndziv Kateryna , Yezhova Olha
Published: December 2022

Background

The Biopsychosocial (BPS) model is recognized and widely accepted in the field of health care, particularly in rehabilitation. However, in clinical practice the applicability of the BPS model is a challenge for many professionals.

Method

This study aimed to explore the factors that impact the perception of rehabilitation professionals about the BPS model in Ukraine. In addition, the job satisfaction assessment was done to measure whether rehabilitation specialists in Ukraine fulfil their professional roles according to their expectations and values. Participants were 346 rehabilitation specialists from Ukraine who completed the Bio-Psycho-Social Scale (BPS) for Use in Healthcare and the Global Job Satisfaction Scale (GJSS). The ANOVA was used to investigate the outcome differences between the two scales.

Results

The highest proportion of responders in this study represented state health services. The BPS subscale outcomes on “assessment and reporting” and “professional knowledge and skills” were significantly higher for specialists from a private sector. The global job satisfaction scale outcomes did not differ between responders from the private and state health sector. The perception of professionals networks was associated with greater job satisfaction.

Conclusions

The findings suggest that conception of the BPS approach in rehabilitation system of Ukraine varies across the private and state settings. The professional network plays important role in job satisfaction of rehabilitation professionals in Ukraine. Future research focusing on education strategies to effectively train professionals to apply biopsychosocial approach to practice is of critical importance to prepare rehabilitation specialists in Ukraine.
Evaluation and countermeasures of contracted services of Chinese family doctors from demanders’ point of view — a case study of a city
Authors: Liu Songyi , Meng Wenqi , Yu Qianqian , Peng Haibo , Jiang Xiaoli , Li Zixin , Yin Wenqiang , Chen Zhongming , Ma Dongping , Sun Kui
Published: December 2022

Background

The “gatekeepers” for residents’ health are their family doctors. The implementation of contracted services provided by family doctors is conducive to promoting hierarchical diagnosis and treatment and achieving the objective of providing residents comprehensive and full-cycle health services. Since its implementation in 2016, the contract service system for Chinese family doctors has yielded a number of results while also highlighting a number of issues that require further investigation. Consequently, the purpose of this study is to assess the impact of family doctors’ contracted services in a Chinese city from the perspective of demanders (i.e., contracted residents), identify the weak links, and then propose optimization strategies.

Methods

In this study, a city in Shandong Province, China was selected as the sample city. In January 2020, 1098 contracted residents (including 40.5% men and 59.5% women) from 18 primary medical institutions (including township health centers and community health centers) were selected for on-site investigation. Take the PCAT-AS(Adult Short) scale revised in Chinese as the research tool to understand the medical experience of contracted residents in primary medical institutions, and interview some family doctors and residents to obtain more in-depth information.

Results

Among the four core dimensions of PCAT-AS, the score of Continuous was the highest (3.44 ± 0.58); The score of Coordinated was the lowest (3.08 ± 0.66); Among the three derived dimensions, the score of Family-centeredness was the highest (3.33 ± 0.65); The score of Culturally-competent was the lowest (2.93 ± 0.77). The types of contracting institutions, residents’ age, marital status, occupation, and whether chronic diseases are confirmed are the influencing factors of PCAT scores.

Conclusion

The family doctors’ contracted services in the city has achieved certain results. At the same time, there are still some problems, such as difficult access to outpatient services during non-working hours, incomplete service items, an imperfect referral system, and inadequate utilization of traditional Chinese medicine services, it is recommended that the government continue to enhance and increase its investment in relevant policies and funds. Primary medical institutions should improve the compensation mechanism for family doctors and increase their work enthusiasm, improve and effectively implement the two-way referral system, gradually form an orderly hierarchical pattern of medical treatment, provide diversified health services in accordance with their own service capacity and the actual needs of residents, and improve the utilization rate of traditional Chinese medicine services in primary medical institutions.
Efficacy and safety of different options for liver regeneration of future liver remnant in patients with liver malignancies: a systematic review and network meta-analysis
Authors: Yi Fengming , Zhang Wei , Feng Long
Published: December 2022

Background

Several treatments induce liver hypertrophy for patients with liver malignancies but insufficient future liver remnant (FLR). Herein, the aim of this study is to compare the efficacy and safety of existing surgical techniques using network meta-analysis (NMA).

Methods

We searched PubMed, Web of Science, and Cochrane Library from databases for abstracts and full-text articles published from database inception through Feb 2022. The primary outcome was the efficacy of different procedures, including standardized FLR (sFLR) increase, time to hepatectomy, resection rate, and R0 resection margin. The secondary outcome was the safety of different treatments, including the rate of Clavien-Dindo≥3a and 90-day mortality.

Results

Twenty-seven studies, including three randomized controlled trials (RCTs), three prospective trials (PTs), and twenty-one retrospective trials (RTs), and a total number of 2075 patients were recruited in this study. NMA demonstrated that the Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) had much higher sFLR increase when compared to portal vein embolization (PVE) (55.25%, 95% CI 45.27–65.24%), or liver venous deprivation(LVD) (43.26%, 95% CI 22.05–64.47%), or two-stage hepatectomy (TSH) (30.53%, 95% CI 16.84–44.21%), or portal vein ligation (PVL) (58.42%, 95% CI 37.62–79.23%). ALPPS showed significantly shorter time to hepatectomy when compared to PVE (−32.79d, 95% CI −42.92–22.66), or LVD (−34.02d, 95% CI −47.85–20.20), or TSH (−22.85d, 95% CI −30.97–14.72), or PVL (−43.37d, 95% CI −64.11–22.62); ALPPS was considered as the highest resection rate when compared to TSH (OR=6.09; 95% CI 2.76–13.41), or PVL (OR =3.52; 95% CI 1.16–10.72), or PVE (OR =4.12; 95% CI 2.19–7.77). ALPPS had comparable resection rate with LVD (OR =2.20; 95% CI 0.83–5.86). There was no significant difference between them when considering the R0 marge rate. ALPPS had a higher Clavien-Dindo≥3a complication rate and 90-day mortality compared to other treatments, although there were no significant differences between different procedures.

Conclusions

ALPPS demonstrated a higher regeneration rate, shorter time to hepatectomy, and higher resection rate than PVL, PVE, or TSH. There was no significant difference between them when considering the R0 marge rate. However, ALPPS developed the trend of higher Clavien-Dindo≥3a complication rate and 90-day mortality compared to other treatments.
Decreased CD44v3 expression impairs endometrial stromal cell proliferation and decidualization in women with recurrent implantation failure
Authors: Zhou Xiaowei , Cao Yi , Zhou Mingjuan , Han Mi , Liu Mengyu , Hu Yanqin , Xu Bufang , Zhang Aijun
Published: December 2022

Background

The precise pathogenesis of poor endometrial receptivity in recurrent implantation failure (RIF) remains unclear. This study was aimed at exploring the effects of different CD44 isoforms in the mid-secretory phase endometrium on endometrial receptivity in women with RIF.

Methods

Mid-secretory phase endometrial tissue samples were obtained from the following two groups of women who had undergone IVF: (a) 24 patients with RIF and (b) 18 patients with infertility due to tubal obstruction, who had achieved a successful clinical pregnancy after the first embryo transfer in IVF (control group). Identification of differentially expressed CD44 isoforms in endometrial tissues was assessed using immunohistochemistry, qPCR, and western blotting. Effects of overexpression and knockdown of CD44v3 on proliferation and decidualization of immortalized human endometrial stromal cells (T-HESCs) and primary HESCs were investigated by qPCR and western blot analysis. A heterologous coculture system of embryo implantation was constructed to mimic the process of trophoblast invasion during implantation.

Results

The expression of CD44v3 was significantly higher in the mid-secretory phase of endometrial stromal cells than in the proliferation phase, but was notably lower in RIF patients. Knockdown of CD44v3 significantly downregulated cell proliferation both in T-HESCs and HESCs. The expression of decidualization markers, prolactin (PRL) and insulin like growth factor binding protein-1 (IGFBP1), was notably decreased following the knockdown of CD44v3, whereas the expression of both PRL and IGFBP1 increased after its overexpression in HESCs. Furthermore, the CD44v3-knockdown HESCs displayed significant deficiency in supporting trophoblast outgrowth in a coculture system of embryo implantation; however, overexpression of CD44v3 in HESCs promoted trophoblast outgrowth.

Conclusion

The reduced expression of CD44v3 suppresses the proliferation and decidualization of HESCs, which might play a pivotal role in poor endometrial receptivity in women with RIF.
Serum interleukin 1β and sP-selectin as biomarkers of inflammation and thrombosis, could they be predictors of disease severity in COVID 19 Egyptian patients? (a cross-sectional study)
Authors: Abd El-Ghani Sara El-Sayed , Hamed Reham Mohammad Raafat , Eid Ragaey Ahmad , Ibrahim Ahmed Yassin Mohammed , Abdel-Hamid Hoda M. , Abdelrahman Walaa , Ibrahim Raghda Ebaid , Abdel-Aziz Manar Mahmoud , Mohamed Marwa Salah
Published: December 2022

Background

Thromboembolism was a chief cause of mortality in 70% of patients with COVID-19. Our objective was to see if serum interleukins 1 beta (IL-1β) and soluble platelets selectin (sP-selectin) could serve as novel markers of thromboembolism in COVID-19 patients.

Methods

This cross sectional study involved 89 COVID-19 patients who were recruited from 1st of February to 1st of May 2021. Clinical and laboratory data were collected, and chest imaging was performed. The levels of IL-1β and sP-selectin were assessed in all cases through ELISA kits. Comparisons between groups were done using an unpaired t-test in normally distributed quantitative variables. In contrast, a non-parametric Mann-Whitney test was used for non-normally distributed quantitative variables.

Results

Severe COVID-19 infection was associated with higher serum levels of CRP, Ferritin, LDH, D dimer, IL-1β and sP-selectin (P <  0.001) with significant correlation between levels of IL-1β and sP-selectin (r 0.37, P <  0.001), D-dimer (r 0.29, P 0.006) and Ferritin (r 0.5, p <  0.001).

Likewise, a positive correlation was also found between levels of sP-selectin, D-dimer and Ferritin (r 0.52, P <  0.001) (r 0.59, P <  0.001). Imaging studies revealed that 9 (10.1%) patients developed venous and 14 (15.7%) developed arterial thrombosis despite receiving anticoagulant therapy. Patients with thrombotic events had significantly higher levels of IL-1β, sP-selectin and LDH serum levels. Meanwhile, there was no statistical significance between CRP, D-dimer or Ferritin levels and the development of thrombotic events.

Conclusion

IL-1β and sP-selectin levels can be promising predictors for severe COVID-19 infection and predictable thrombosis.
Comparison of the healthcare system of Chile and Brazil: strengths, inefficiencies, and expenditures
Authors: Cerda Arcadio A. , García Leidy Y. , Rivera-Arroyo Jennifer , Riquelme Andrés , Teixeira Joao Paulo , Jakovljevic Mihajlo
Published: December 2022

Background

Governments in Latin America are constantly facing the problem of managing scarce resources to satisfy alternative needs, such as housing, education, food, and healthcare security. Those needs, combined with increasing crime levels, require financial resources to be solved.

Objective

The objective of this review was to characterizar the health system and health expenditure of a large country (Brazil) and a small country (Chile) and identify some of the challenges these two countries face in improving the health services of their population.

Methods

A literature review was conducted by searching journals, databases, and other electronic resources to identify articles and research publications describing health systems in Brazil and Chile.

Results

The review showed that the economic restriction and the economic cycle have an impact on the funding of the public health system. This result was true for the Brazilian health system after 2016, despite the change to a unique health system one decade earlier. In the case of Chile, there are different positions about which one is the best health system: a dual public and private or just public one. As a result, a referendum on September 4, 2022, of a new constitution, which incorporated a unique health system, was rejected. At the same time, the Government ended the copayment in the public health system in September 2022, excluding illnesses referred to the private sector. Another issue detected was the fragility of the public and private sector coverage due to the lack of funding.

Conclusions

The health care system in Chile and Brazil has improved in the last decades. However, the public healthcare systems still need additional funding and efficiency improvement to respond to the growing health requirements needed from the population.
Stage-specific requirement for METTL3-dependent m6A modification during dental pulp stem cell differentiation
Authors: Luo Haiyun , Liu Wenjing , Zhou Yachuan , Zhang Yanli , Wu Junrong , Wang Ruolan , Shao Longquan
Published: December 2022

Background

N6-methyladenosine (m6A) is the most prevalent epigenetic modification in eukaryotic messenger RNAs and plays a critical role in cell fate transition. However, it remains to be elucidated how m6A marks functionally impact the transcriptional cascades that orchestrate stem cell differentiation. The present study focuses on the biological function and mechanism of m6A methylation in dental pulp stem cell (DPSC) differentiation.

Methods

m6A RNA immunoprecipitation sequencing was utilized to assess the m6A-mRNA landscape during DPSC differentiation. Ectopic transplantation of DPSCs in immunodeficient mice was conducted to verify the in vitro findings. RNA sequencing and m6A RNA immunoprecipitation sequencing were combined to identify the candidate targets. RNA immunoprecipitation and RNA/protein stability of Noggin (NOG) were evaluated. The alteration in poly(A) tail was measured by 3′-RACE and poly(A) tail length assays.

Results

We characterized a dynamic m6A-mRNA landscape during DPSC mineralization with increasing enrichment in the 3′ untranslated region (UTR). Methyltransferase-like 3 (METTL3) was identified as the key m6A player, and METTL3 knockdown disrupted functional DPSC differentiation. Moreover, METTL3 overexpression enhanced DPSC mineralization. Increasing m6A deposition in the 3′ UTR restricted NOG expression, which is required for DPSC mineralization. This stage-specific m6A methylation and destabilization of NOG was suppressed by METTL3 knockdown only in differentiated DPSCs. Furthermore, METTL3 promotes the degradation of m6A-tagged NOG by shortening the poly(A) tail length in the differentiated stage.

Conclusions

Our results address an essential role of dynamic m6A signaling in the temporal control of DPSC differentiation and provide new insight into epitranscriptomic mechanisms in stem cell-based therapy.
Uncovering the gene regulatory network of type 2 diabetes through multi-omic data integration
Authors: Liu Jiachen , Liu Shenghua , Yu Zhaomei , Qiu Xiaorui , Jiang Rundong , Li Weizheng
Published: December 2022

Background

Type 2 diabetes (T2D) onset is a complex, organized biological process with multilevel regulation, and its physiopathological mechanisms are yet to be elucidated. This study aims to find out the key drivers and pathways involved in the pathogenesis of T2D through multi-omics analysis.

Methods

The datasets used in the experiments comprise three groups: (1) genomic (2) transcriptomic, and (3) epigenomic categories. Then, a series of bioinformatics technologies including Marker set enrichment analysis (MSEA), weighted key driver analysis (wKDA) was performed to identify key drivers. The hub genes were further verified by the Receiver Operator Characteristic (ROC) Curve analysis, proteomic analysis, and Real-time quantitative polymerase chain reaction (RT-qPCR). The multi-omics network was applied to the Pharmomics pipeline in Mergeomics to identify drug candidates for T2D treatment. Then, we used the drug-gene interaction network to conduct network pharmacological analysis. Besides, molecular docking was performed using AutoDock/Vina, a computational docking program.

Results

Module-gene interaction network was constructed using MSEA, which revealed a significant enrichment of immune-related activities and glucose metabolism. Top 10 key drivers (PSMB9, COL1A1, COL4A1, HLA-DQB1, COL3A1, IRF7, COL5A1, CD74, HLA-DQA1, and HLA-DRB1) were selected by wKDA analysis. Among these, COL5A1, IRF7, CD74, and HLA-DRB1 were verified to have the capability to diagnose T2D, and expression levels of PSMB9 and CD74 had significantly higher in T2D patients. We further predict the co-expression network and transcription factor (TF) binding specificity of the key driver. Besides, based on module interaction networks and key driver networks, 17 compounds are considered to possess T2D-control potential, such as sunitinib.

Conclusions

We identified signature genes, biomolecular processes, and pathways using multi-omics networks. Moreover, our computational network analysis revealed potential novel strategies for pharmacologic interventions of T2D.
Bovine neutrophil chemotaxis to Listeria monocytogenes in neurolisteriosis depends on microglia-released rather than bacterial factors
Authors: Bagatella Stefano , Haghayegh Jahromi Neda , Monney Camille , Polidori Margherita , Gall Flavio Max , Marchionatti Emma , Serra Fabienne , Riedl Rainer , Engelhardt Britta , Oevermann Anna
Published: December 2022

Background

Listeria monocytogenes(Lm) is a bacterial pathogen of major concern for humans and ruminants due to its neuroinvasive potential and its ability to cause deadly encephalitis (neurolisteriosis). On one hand, polymorphonuclear neutrophils (PMN) are key players in the defense againstLm, but on the other hand intracerebral infiltration with PMN is associated with significant neural tissue damage.Lm-PMN interactions in neurolisteriosis are poorly investigated, and factors inducing PMN chemotaxis to infectious foci containingLmin the central nervous system (CNS) remain unidentified.

Methods

In this study, we assessed bovine PMN chemotaxis towardsLmand supernatants of infected endogenous brain cell populations in ex vivo chemotaxis assays, to identify chemotactic stimuli for PMN chemotaxis towardsLmin the brain. In addition, microglial secretion of IL-8 was assessed both ex vivo and in situ.

Results

Our data show that neitherLmcell wall components nor intact bacteria elicit chemotaxis of bovine PMN ex vivo. Moreover, astrocytes and neural cells fail to induce bovine PMN chemotaxis upon infection. In contrast, supernatant fromLminfected microglia readily induced chemotaxis of bovine PMN. Microglial expression and secretion of IL-8 was identified during earlyLminfection in vitro and in situ, although IL-8 blocking with a specific antibody could not abrogate PMN chemotaxis towardsLminfected microglial supernatant.

Conclusions

These data provide evidence that host-derived rather than bacterial factors trigger PMN chemotaxis to bacterial foci in the CNS, that microglia have a primary role as initiators of bovine PMN chemotaxis into the brain during neurolisteriosis and that blockade of these factors could be a therapeutic target to limit intrathecal PMN chemotaxis and PMN associated damage in neurolisteriosis.
Lung inflammation induced by silica particles triggers hippocampal inflammation, synapse damage and memory impairment in mice
Authors: Suman Patrick R. , Souza Lisiane S. , Kincheski Grasielle C. , Melo Helen M. , Machado Mariana N. , Carvalho Giovanna M. C. , De Felice Fernanda G. , Zin Walter A. , Ferreira Sergio T.
Published: December 2022

Background

Considerable evidence indicates that a signaling crosstalk between the brain and periphery plays important roles in neurological disorders, and that both acute and chronic peripheral inflammation can produce brain changes leading to cognitive impairments. Recent clinical and epidemiological studies have revealed an increased risk of cognitive impairment and dementia in individuals with impaired pulmonary function. However, the mechanistic underpinnings of this association remain unknown. Exposure to SiO2 (silica) particles triggers lung inflammation, including infiltration by peripheral immune cells and upregulation of pro-inflammatory cytokines. We here utilized a mouse model of lung silicosis to investigate the crosstalk between lung inflammation and memory.

Methods

Silicosis was induced by intratracheal administration of a single dose of 2.5 mg SiO2/kg in mice. Molecular and behavioral measurements were conducted 24 h and 15 days after silica administration. Lung and hippocampal inflammation were investigated by histological analysis and by determination of pro-inflammatory cytokines. Hippocampal synapse damage, amyloid-β (Aβ) peptide content and phosphorylation of Akt, a proxy of hippocampal insulin signaling, were investigated by Western blotting and ELISA. Memory was assessed using the open field and novel object recognition tests.

Results

Administration of silica induced alveolar collapse, lung infiltration by polymorphonuclear (PMN) cells, and increased lung pro-inflammatory cytokines. Lung inflammation was followed by upregulation of hippocampal pro-inflammatory cytokines, synapse damage, accumulation of the Aβ peptide, and memory impairment in mice.

Conclusion

The current study identified a crosstalk between lung and brain inflammatory responses leading to hippocampal synapse damage and memory impairment after exposure to a single low dose of silica in mice.
Angiotensin(1–7) attenuates visceral adipose tissue expansion and lipogenesis by suppression of endoplasmic reticulum stress via Mas receptor
Authors: Ma Chifa , Shi Tingting , Song Lini , Liu Jingyi , Yuan Mingxia
Published: December 2022

Background

White adipose tissue can be classified based on its location as subcutaneous and visceral fat, and the latter accumulation is reported to be more detrimental to metabolism. Endoplasmic reticulum (ER) stress has been demonstrated to regulate lipogenesis. The peptide angiotensin(1–7) [Ang(1–7)], which can be produced from angiotensin II (AngII) by angiotensin-converting enzyme 2 (ACE2), plays its role through Mas receptor, also participates in the regulation of lipid metabolism in adipose tissue, however, whether ER stress is involved in the mechanism remains unclear. Therefore, we aimed to explore the role of Ang(1–7) pathway in regulating visceral adipose tissue expansion and ER stress.

Methods

ACE2 knockout (KO), Mas KO and C57BL/6 J mice were fed with high fat diet. Db/db mice were treated with either normal saline, Ang(1–7) or Ang(1–7) combined with Mas receptor inhibitor A779 using mini osmotic pumps. Fat mass was weighted, fat distribution was evaluated by MRI, and lipid profile and adipokines in epididymal adipose tissue were measured by ELISA kits, and histology of epididymal adipose tissue was also analyzed in multiple animal models. Additionally, differentiated 3T3-L1 cells were pre-loaded with palmitic acid to induce ER stress, then treated with drugs as those administrated to db/db mice. ER stress and lipogenesis related proteins in mice adipose and differentiated 3T3L-1 cells were analyzed by Western blot.

Results

ACE2 or Mas KO mice exhibited increased visceral adipose tissue, adipocyte size and protein expression of lipogenesis and ER stress related markers in epididymal adipose tissue compared to wild-type mice. Db/db mice treated with Ang(1–7) displayed decreased visceral fat mass, adipocyte size and protein expression of lipogenesis and ER stress markers in epididymal adipose tissue compared to those treated with normal saline, while A779 partly attenuated these effects. Additionally, Ang(1–7) improved ER stress and lipogenesis markers in differentiated 3T3-L1 cells pre-loaded with palmitic acid.

Conclusions

Our findings indicated that Ang(1–7) attenuated visceral adipose tissue expansion and lipogenesis by suppression of ER stress via Mas receptor. The present study provides a potential perspective for Ang(1–7) for the therapeutics of obesity and related disorders.
Treatment persistence in patients with schizophrenia treated with lurasidone in Italian clinical practice
Authors: Fagiolini Andrea , Olivola Miriam , Lavatelli Lisa , Bellomo Antonello , Lobaccaro Caterina , Falsetto Nathalie , Micillo Marco , Cuomo Alessandro
Published: December 2022

Background and rationale

Treatment persistence combines clinician and patient judgment of efficacy, tolerability and safety into a comprehensive measure of effectiveness and is defined as the act of continuing a treatment over time. Studies have reported poor treatment persistence to antipsychotic medications in patients with schizophrenia. This study evaluated treatment persistence to lurasidone (LUR) in patients with schizophrenia in a real-world Italian setting.

Methods

This was a retrospective observational study of patients with schizophrenia who started treatment with LUR ≥ 6 months before inclusion. Following informed consent, data were collected starting from the index date (start of LUR treatment) at all visits occurring as per clinical practice. The primary endpoint was treatment persistence during the first 6 months, defined as the time between index date and all-cause discontinuation. Patients treated with LUR > 180 days were considered persistent. As secondary endpoint, treatment persistence was evaluated for a period of  ≥ 18 months.

Results

Forty-five patients were enrolled and 41 (91.11%) completed the study. Forty-one patients (91.11%) were included in the eligible population as they initiated LUR treatment  ≥ 6 months before data collection.

Patients were 43.0 ± 15.89 years old and 61% were female. Twenty-two patients (53.66%) started LUR treatment in a hospital setting and 19 (46.34%) in an outpatient setting. Based on Clinical Global Impression—Severity scale (CGI-S) at LUR initiation, 12 patients (29.27%) were severely ill, 17.07% markedly ill, 19.51% moderately ill, 2.44% mildly ill and 4.88% borderline mentally ill. Thirty-two patients (78.05%) were treatment persistent for  ≥ 180 days. Among the 19 patients observed for  ≥ 18 months, 11 (57.89%) were persistent for  ≥ 18 months. Among the 22 study patients observed for  < 18 months, 12 (54.54%) were persistent. An improvement in schizophrenia severity according to CGI-S was observed at inclusion (following LUR therapy) compared to the index date. Six patients (14.63%) experienced at least one adverse drug reaction: akathisia (7.32%), extrapyramidal disorder (4.88%), hyperprolactinemia (2.44%), restlessness (2.44%), and galactorrhea (2.44%). None were serious.

Conclusions

Persistence to LUR in patients with schizophrenia was relatively high: 78% and 58% of patients were still on LUR after 6 and 18 months of treatment, respectively. This may reflect LUR’s relatively favorable balance between efficacy and tolerability, as well as favorable patient satisfaction and acceptance.
Repair of exposure and fracture of the porous high-density polyethylene framework after ear reconstruction
Authors: Jiang Chenyan , Chen Bin , Lu Lixing , Yan Xiaojun , Yi Bin , Shi Runjie
Published: December 2022

Objective

To assess the repair method of exposure or fracture of the porous high-density polyethylene ear framework after total auricle reconstruction.

Study design

A prospective case study.

Methods

From April 2018 to October 2021, 11 patients with framework exposure or fracture after total auricle reconstruction were admitted to the hospital for repair. In these 11 patients, the repair was performed using (1) a temporal muscle flap combined with free skin graft in 5 patients, (2) a mastoid fascia flap combined with free skin graft in 2 patients, (3) a simple local skin flap in 1 patient, (4) combination of a temporalis muscle flap and a mastoid fascia flap together with free skin graft in 2 patients, and (5) a Su-Por helix material combined with a temporal muscle flap and free skin graft in 1 patient.

Results

After follow-up for 3–36 months, except for one patient in whom local exposure again occurred at the same site, the framework was in a good shape in the other patients, and all the skin graft survived.

Conclusion

The defect of the upper part of the auricle can be repaired using a temporal muscle flap combined with temporal muscle fascia and skin graft. The defect of the middle and lower part of the auricle can be repaired using a mastoid fascia flap combined with skin graft. For framework fracture, the damaged site can be first strengthened with another ear material and then combined with the adjacent fascia flap and free skin graft.