bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of dropout rates in the preclinical years and contributing factors: a study on one Thai medical school
Authors: Wainipitapong Sorawit , Chiddaycha Mayteewat
Published: June 2022

Background

The highest dropout rate for medical students is during the preclinical years of education. Several studies have reported possible contributing factors, however, studies regarding the dropout rate from medical education among Thai medical students and its associated factors are still lacking. This study aimed to identify the prevalence of dropout from medical education within the preclinical period and its associated factors among Thai medical students.

Methods

We collected data from preclinical medical students who entered one medical school in Bangkok, Thailand, between 2017–2019. Demographic data, admission program, pre-admission mental health status assessed by the Thai Mental Health Indicator 66, mental health records from the faculty-based counseling services, and academic achievement were extracted. Data were reported in a descriptive fashion. We analyzed the association between dropout and these factors by robust Poisson regression.

Results

In total, 914 students were recruited. Dropout was only 1.5%, which was lower than the previous studies. Regression analysis showed a significant association between dropout and mental health problems [Prevalence ratio (PR) 58.20, 95%CI 13.72- 246.95] but not admission program [PR 0.32, 95%CI 0.09 – 1.16] or failing examinations [PR 0.59, 95%CI 0.18 – 1.90]. However, other contributing factors such as financial status, family problems, medical illness, and students’ motivation, were not evaluated in this study.

Conclusions

Mental health problems during medical education were associated with dropout after adjusting for other confounding variables. Further longitudinal studies are needed to identify the impacts of academic failure on dropout in higher clinical years.
Mining comorbidities of opioid use disorder from FDA adverse event reporting system and patient electronic health records
Authors: Pan Yiheng , Xu Rong
Published: June 2022

Background

Opioid use disorder (OUD) has become an urgent health problem. People with OUD often experience comorbid medical conditions. Systematical approaches to identifying co-occurring conditions of OUD can facilitate a deeper understanding of OUD mechanisms and drug discovery. This study presents an integrated approach combining data mining, network construction and ranking, and hypothesis-driven case–control studies using patient electronic health records (EHRs).

Methods

First, we mined comorbidities from the US Food and Drug Administration Adverse Event Reporting System (FAERS) of 12 million unique case reports using frequent pattern-growth algorithm. The performance of OUD comorbidity mining was measured by precision and recall using manually curated known OUD comorbidities. We then constructed a disease comorbidity network using mined association rules and further prioritized OUD comorbidities. Last, novel OUD comorbidities were independently tested using EHRs of 75 million unique patients.

Results

The OUD comorbidities from association rules mining achieves a precision of 38.7% and a recall of 78.2 Based on the mined rules, the global DCN was constructed with 1916 nodes and 32,175 edges. The network-based OUD ranking result shows that 43 of 55 known OUD comorbidities were in the first decile with a precision of 78.2%. Hypothyroidism and type 2 diabetes were two top-ranked novel OUD comorbidities identified by data mining and network ranking algorithms. Based on EHR-based case–control studies, we showed that patients with OUD had significantly increased risk for hyperthyroidism (AOR = 1.46, 95% CI 1.43–1.49,pvalue < 0.001), hypothyroidism (AOR = 1.45, 95% CI 1.42–1.48,pvalue < 0.001), type 2-diabetes (AOR = 1.28, 95% CI 1.26–1.29,pvalue < 0.001), compared with individuals without OUD.

Conclusion

Our study developed an integrated approach for identifying and validating novel OUD comorbidities from health records of 87 million unique patients (12 million for discovery and 75 million for validation), which can offer new opportunities for OUD mechanism understanding, drug discovery, and multi-component service delivery for co-occurring medical conditions among patients with OUD.
Nursing students’ experiences of educational discrimination: a qualitative study
Authors: Hadian Jazi Zahra , Gheybi Kazzem , Zare Zahra , Shahsavari Hooman
Published: June 2022

Background

Although the need for justice and the elimination of injustice (or discrimination) is now a universally accepted principle, discrimination is still an unpleasant experience for many nursing students. This study aimed to explain the experiences of nursing students of educational discrimination and find out the main factors that cause this feeling.

Methods

This is a qualitative study conducted in the nursing faculty of Shahr-e-Kord and the Iran university of medical science (IUMS) in Iran. Twelve nursing students were selected by purposeful sampling method and data were collected through face-to-face and in-depth interviews with semi-structured questions. All interviews were analyzed according to the content analysis method.

Results

Three main themes and ten subcategories appeared. Extracted themes include: "inappropriate behavior of nursing professors (or instructors) " with 3 subcategories (1- discriminatory behavior by nursing professors (or instructors), 2- lack of sufficient self-confidence in nursing professors and transferring it to the student, and 3- the educator role in motivating or eliminating motivation); "Strict rules" with 3 subcategories (1- inequality in implementation of rights and rules among students of different disciplines, 2- differences in compliance with laws and regulations, and 3- nurses are being strictly monitored), and " Lack of nursing professional independence " with 4 subcategories (1- lack of authority, 2- lack of supportive organizations for nurses, 3- lack of proper social status of nursing in society, and 4- the high authority and power of physicians over other disciplines).

Conclusions

In our study, it was shown that nursing students feel the most discrimination in front of medical students. Feelings of discrimination reduce self-confidence in nursing students. Therefore, nursing educators and professors must think of a solution, or at least they should not cause this feeling in them through inappropriate behavior and discriminatory speech and words.
Anillin governs mitotic rounding during early epidermal development
Authors: Mahly Adnan , Padmanabhan Krishnanand , Soffer Arad , Cohen Jonathan , Omar Jana , Sagi-Eisenberg Ronit , Luxenburg Chen
Published: June 2022

Background

The establishment of tissue architecture requires coordination between distinct processes including basement membrane assembly, cell adhesion, and polarity; however, the underlying mechanisms remain poorly understood. The actin cytoskeleton is ideally situated to orchestrate tissue morphogenesis due to its roles in mechanical, structural, and regulatory processes. However, the function of many pivotal actin-binding proteins in mammalian development is poorly understood.

Results

Here, we identify a crucial role for anillin (ANLN), an actin-binding protein, in orchestrating epidermal morphogenesis. In utero RNAi-mediated silencing ofAnlnin mouse embryos disrupted epidermal architecture marked by adhesion, polarity, and basement membrane defects. Unexpectedly, these defects cannot explain the profoundly perturbed epidermis ofAnln-depleted embryos. Indeed, even before these defects emerge,Anln-depleted epidermis exhibits abnormalities in mitotic rounding and its associated processes: chromosome segregation, spindle orientation, and mitotic progression, though not in cytokinesis that was disrupted only inAnln-depleted cultured keratinocytes. We further show that ANLN localizes to the cell cortex during mitotic rounding, where it regulates the distribution of active RhoA and the levels, activity, and structural organization of the cortical actomyosin proteins.

Conclusions

Our results demonstrate that ANLN is a major regulator of epidermal morphogenesis and identify a novel role for ANLN in mitotic rounding, a near-universal process that governs cell shape, fate, and tissue morphogenesis.
To kill or to be killed: pangenome analysis of Escherichia coli strains reveals a tailocin specific for pandemic ST131
Authors: Tantoso Erwin , Eisenhaber Birgit , Kirsch Miles , Shitov Vladimir , Zhao Zhiya , Eisenhaber Frank
Published: June 2022

Background

Escherichia coli(E. coli) has been one of the most studied model organisms in the history of life sciences. Initially thought just to be commensal bacteria,E. colihas shown wide phenotypic diversity including pathogenic isolates with great relevance to public health. Though pangenome analysis has been attempted several times, there is no systematic functional characterization of theE. colisubgroups according to the gene profile.

Results

Systematically scanning for optimal parametrization, we have built theE. colipangenome from 1324 complete genomes. The pangenome size is estimated to be ~25,000 gene families (GFs). Whereas the core genome diminishes as more genomes are added, the softcore genome (≥95% of strains) is stable with ~3000 GFs regardless of the total number of genomes. Apparently, the softcore genome (with a 92% or 95% generation threshold) can define the genome of a bacterial species listing the critically relevant, evolutionarily most conserved or important classes of GFs. Unsupervised clustering of commonE. colisequence types using the presence/absence GF matrix reveals distinct characteristics ofE. coliphylogroups B1, B2, and E. We highlight the bi-lineage nature of B1, the variation of the secretion and of the iron acquisition systems in ST11 (E), and the incorporation of a highly conserved prophage into the genome of ST131 (B2). The tail structure of the prophage is evolutionarily related to R2-pyocin (a tailocin) fromPseudomonas aeruginosaPAO1. We hypothesize that this molecular machinery is highly likely to play an important role in protecting its own colonies; thus, contributing towards the rapid rise of pandemicE. coliST131.

Conclusions

This study has explored the optimized pangenome development inE. coli. We provide complete GF lists and the pangenome matrix as supplementary data for further studies. We identified biological characteristics of differentE. colisubtypes, specifically for phylogroups B1, B2, and E. We found an operon-like genome region coding for a tailocin specific for ST131 strains. The latter is a potential killer weapon providing pandemicE. coliST131 with an advantage in inter-bacterial competition and, suggestively, explains their dominance as human pathogen amongE. colistrains.
Projecting vaccine demand and impact for emerging zoonotic pathogens
Authors: Lerch Anita , ten Bosch Quirine A. , L’Azou Jackson Maïna , Bettis Alison A. , Bernuzzi Mauro , Murphy Georgina A. V. , Tran Quan M. , Huber John H. , Siraj Amir S. , Bron Gebbiena M. , Elliott Margaret , Hartlage Carson S. , Koh Sojung , Strimbu Kathyrn , Walters Magdalene , Perkins T. Alex , Moore Sean M.
Published: June 2022

Background

Despite large outbreaks in humans seeming improbable for a number of zoonotic pathogens, several pose a concern due to their epidemiological characteristics and evolutionary potential. To enable effective responses to these pathogens in the event that they undergo future emergence, the Coalition for Epidemic Preparedness Innovations is advancing the development of vaccines for several pathogens prioritized by the World Health Organization. A major challenge in this pursuit is anticipating demand for a vaccine stockpile to support outbreak response.

Methods

We developed a modeling framework for outbreak response for emerging zoonoses under three reactive vaccination strategies to assess sustainable vaccine manufacturing needs, vaccine stockpile requirements, and the potential impact of the outbreak response. This framework incorporates geographically variable zoonotic spillover rates, human-to-human transmission, and the implementation of reactive vaccination campaigns in response to disease outbreaks. As proof of concept, we applied the framework to four priority pathogens: Lassa virus, Nipah virus, MERS coronavirus, and Rift Valley virus.

Results

Annual vaccine regimen requirements for a population-wide strategy ranged from > 670,000 (95% prediction interval 0–3,630,000) regimens for Lassa virus to 1,190,000 (95% PrI 0–8,480,000) regimens for Rift Valley fever virus, while the regimens required for ring vaccination or targeting healthcare workers (HCWs) were several orders of magnitude lower (between 1/25 and 1/700) than those required by a population-wide strategy. For each pathogen and vaccination strategy, reactive vaccination typically prevented fewer than 10% of cases, because of their presently low R0 values. Targeting HCWs had a higher per-regimen impact than population-wide vaccination.

Conclusions

Our framework provides a flexible methodology for estimating vaccine stockpile needs and the geographic distribution of demand under a range of outbreak response scenarios. Uncertainties in our model estimates highlight several knowledge gaps that need to be addressed to target vulnerable populations more accurately. These include surveillance gaps that mask the true geographic distribution of each pathogen, details of key routes of spillover from animal reservoirs to humans, and the role of human-to-human transmission outside of healthcare settings. In addition, our estimates are based on the current epidemiology of each pathogen, but pathogen evolution could alter vaccine stockpile requirements.
Autofluorescence detection and co-axial projection for intraoperative localization of parathyroid gland
Authors: Chen Wei , Ma Xiaopeng , Shao Pengfei , Liu Peng , Xu Ronald X.
Published: June 2022

Background

Near-infrared (NIR) autofluorescence detection is an effective method for identifying parathyroid glands (PGs) in thyroidectomy or parathyroidectomy. Fiber optical probes provide quantitative autofluorescence measurements for PG detection owing to its high sensitivity and high excitation light cut-off efficiency at a fixed detection distance. However, an optical fiber probe lacks the imaging capability and cannot map the autofluorescence distribution on top of normal tissue background. Therefore, there is a need for intraoperative mapping of PGs with high sensitivity and imaging resolution.

Methods

We have developed a fluorescence scanning and projection (FSP) system that combines a scanning probe and a co-axial projector for intraoperative localization and in situ display of PGs. Some of the key performance characteristics, including spatial resolution and sensitivity for detection, spatial resolution for imaging, dynamic time latency, and PG localization capability, are characterized and verified by benchtop experiments. Clinical utility of the system is simulated by a fluorescence-guided PG localization surgery on a tissue-simulating phantom and validated in an ex vivo experiment.

Results

The system is able to detect indocyanine green (ICG) solution of 5 pM at a high signal-to-noise ratio (SNR). Additionally, it has a maximal projection error of 0.92 mm, an averaged projection error of 0.5 ± 0.23 mm, and an imaging resolution of 748 μm at a working distance ranging from 35 to 55 cm. The dynamic testing yields a short latency of 153 ± 54 ms, allowing for intraoperative scanning on target tissue during a surgical intervention. The simulated fluorescence-guided PG localization surgery has validated the system’s capability to locate PG phantom with operating room ambient light interference. The simulation experiment on the PG phantom yields a position detection bias of 0.36 ± 0.17 mm, and an area intersection over unit (IoU) of 76.6% ± 6.4%. Fluorescence intensity attenuates exponentially with the thickness of covered tissue over the PG phantom, indicating the need to remove surrounding tissue in order to reveal the weak autofluorescence signal from PGs. The ex vivo experiment demonstrates the technical feasibility of the FSP system for intraoperative PG localization with accuracy.

Conclusion

We have developed a novel probe-based imaging and navigation system with high sensitivity for fluorescence detection, capability for fluorescence image reconstruction, multimodal image fusion and in situ PG display function. Our studies have demonstrated its clinical potential for intraoperative localization and in situ display of PGs in thyroidectomy or parathyroidectomy.
Cavitation assisted endoplasmic reticulum targeted sonodynamic droplets to enhanced anti-PD-L1 immunotherapy in pancreatic cancer
Authors: Chen Jifan , Feng Liting , Jin Peile , Shen Jiaxin , Lu Jiayue , Song Yue , Wang Guowei , Chen Qin , Huang Deyi , Zhang Ying , Zhang Chao , Xu Youfeng , Huang Pintong
Published: June 2022

Background

Sonodynamic therapy (SDT) induces immunogenic cell death (ICD) in tumors and promises to play an assistive role in immunotherapy in pancreatic cancer. However, the short half-life and limited diffusion distance of reactive oxygen species (ROS) impair ICD induction, especially in tumors with relatively poor blood perfusion and dense stroma.

Results

To address this problem, we fabricated cavitation-assisted endoplasmic reticulum (ER) targeted sonodynamic nanodroplets (PMPS NDs, 329 nm). The good sonodynamic effect and precise endoplasmic reticulum target effect was verified. After intravenous injection, the cRGD peptide modified nanodroplets initially aggregated around the tumor vascular endothelial cells. Stimulated by ultrasound, the liquid-to-gas bubbles began to oscillate and cavitate. This acoustic droplet evaporation strategy facilitated transport of the nanoparticle across the vessel, with deep penetration. This loosened the tumor stroma and facilitated accumulation and penetration of loaded sonosensitizer after 6 h. The modified sonosensitizer can selectively accumulate in the ER to generate a large amount of ROS in situ, inducing potent ER stress, amplified ICD and dendritic cell maturation in vitro and in vivo. Furthermore, the elevated antitumor effect of SDT plus anti-PD-L1 immunotherapy was verified using an orthotopic tumor model.

Conclusions

This study reports a cavitation assisted ER targeted sonodynamic therapy that can enhance the effect of anti-PD-L1 immunotherapy effectively in orthotopic and distant pancreatic cancer.

Graphical Abstract
Comparison of the measurement properties of SF-6Dv2 and EQ-5D-5L in a Chinese population health survey
Authors: Xie Shitong , Wang Dingyao , Wu Jing , Liu Chunyu , Jiang Wenchen
Published: June 2022

Background

SF-6Dv2, the latest version of SF-6D, has been developed recently, and its measurement properties remain to be evaluated and compared with the EQ-5D-5L. The aim of this study was to assess and compare the measurement properties of the SF-6Dv2 and the EQ-5D-5L in a large-sample health survey among the Chinese population.

Methods

Data were obtained from the 2020 Health Service Survey in Tianjin, China. Respondents were randomly selected and invited to complete both the EQ-5D-5L and SF-6Dv2 through face-to-face interviews or self-administration. Health utility values were calculated by the Chinese value sets for the two measures. Ceiling and floor effects were firstly evaluated. Convergent validity and discriminate validity were examined using Spearman’s rank correlation and effect sizes, respectively. The agreement was assessed using intraclass correlation coefficients (ICC). Sensitivity was compared using relative efficiency and receiver operating characteristic.

Results

Among 19,177 respondents (49.3% male, mean age 55.2 years, ranged 18–102 years) included in this study, the mean utility was 0.939 (0.168) for EQ-5D-5L and 0.872 (0.184) for SF-6Dv2. A higher ceiling effect was observed in EQ-5D-5L than in SF-6Dv2 (72.8% vs. 36.1%). The Spearman’s rank correlation (range: 0.30–0.69) indicated an acceptable convergent validity between the dimensions of EQ-5D-5L and SF-6Dv2. The SF-6Dv2 showed slightly better discriminative capacities than the EQ-5D-5L (ES: 0.126–2.675 vs. 0.061–2.256). The ICC between the EQ-5D-5L and SF-6Dv2 utility values of the total sample was 0.780 (p < 0.05). The SF-6Dv2 had 29.0–179.2% higher efficiency than the EQ-5D-5L at distinguishing between respondents with different external health indicators, while the EQ-5D-5L was found to be 8.2% more efficient at detecting differences in self-reported health status than the SF-6Dv2.

Conclusions

Both the SF-6Dv2 and EQ-5D-5L have been demonstrated to be comparably valid and sensitive when used in Chinese population health surveys. The two measures may not be interchangeable given the moderate ICC and the systematic difference in utility values between the SF-6Dv2 and EQ-5D-5L. Further research is warranted to compare the test–retest reliability and responsiveness.
Evaluate the diagnostic and prognostic value of NUSAP1 in papillary thyroid carcinoma and identify the relationship with genes, proteins, and immune factors
Authors: Gao Tiantian , Zhao Lei , Zhang Fan , Cao Conghui , Fan Shuting , Shi Xiaoguang
Published: June 2022

Background

Nucleolar spindle-associated protein 1 (NUSAP1) is reported to be a useful diagnostic and prognostic marker for a variety of cancers, but relevant studies are lacking in papillary thyroid carcinoma (PTC).

Methods

The relationship between NUSAP1 expression and the overall survival (OS) of pan-cancer was examined by GEPIA and KMplot. We explored the relationship between NUSAP1 and clinical PTC data based on the THCA dataset of TCGA and the GEO dataset of NCBI; GO, KEGG analysis, and ceRNA networks were performed on co-expressed genes through LinkedOmics and Starbase. We assessed the relevance between NUSAP1 and the tumor microenvironment using ESTIMATE, correlations between NUSAP1 and immune cells with TIMER, the relationship between NUSAP1 and immunotherapy by TCIA, and small-molecule drugs targeting NUSAP1 that can be discovered using the CMap database.

Results

Higher expression of NUSAP1 in pan-cancer tissues was correlated with shorter OS. NUSAP1 was also significantly expressed in PTC tissues and was an independent prognostic risk factor. Compared to the NUSAP1 low expression group, the NUSAP1 high expression group was more likely to also have lymph node metastasis, pathological PTC type, shorter progression-free survival (PFS), and higher scores for immune checkpoint inhibitor treatment. The genes associated with NUSAP1 were mostly involved in the cell cycle, immune-related pathways, and AITD. Ten lncRNAs (GAS5, SNHG7, UCA1, SNHG1, HCP5, DLEU2, HOTAIR, TP53TG1, SNHG12, C9orf106), eleven miRNAs (hsa-miR-10a-5p, hsa-miR-10b-5p, hsa-miR-18a-5p, hsa-miR-18b-5p, hsa-miR-128-3p, hsa-miR-214-3p, hsa-miR-219a-2-3p, hsa-miR-339-5p, hsa-miR-494-3p, hsa-miR-545-3p, hsa-miR-769-5p), and one mRNA (NUSAP1) were constructed. NUSAP1 participated in the formation of the tumor microenvironment. CMap predicted the 10 most important small molecules about NUSAP1.

Conclusions

In PTC, NUSAP1 shows good diagnostic value and prognostic value; NUSAP1 impacts the cell cycle, immune-related pathways, and AITD and has a complex effect on the tumor microenvironment in PTC.
Study on the expression of c-Met in gastric cancer and its correlation with preoperative serum tumor markers and prognosis
Authors: Zhang Zhengchao , Miao Lele , Wang Song , Zhao Yang , Xie Yongqiang , Yun Heng , Ren Zhijian , Wang Guan , Teng Muzhou , Li Yumin
Published: June 2022

Background

Studies have found that c-Met plays a critical role in the progression of solid tumors. This study aimed to investigate the expression of c-Met in gastric cancer (GC) and its correlation with preoperative serum tumor markers and prognosis, in order to provide a more theoretical basis for targeting c-Met in the treatment of GC.

Methods

Ninety-seven patients who underwent curative gastrectomy in our hospital from December 2013 to September 2015 were included in this study. The tissue microarray was constructed by paraffin-embedded tumor tissue of enrolled patients, including 97 GC points and 83 paracancerous points. Then, it was used for c-Met immunohistochemical staining, followed by an immunological H-score. The clinical baseline data and 5-year survival of patients with low and high c-Met expression were compared. Besides, the correlation between the expression of c-Met in tumor tissues and preoperative serum tumor markers was investigated. Finally, multivariate Cox regression analysis was used to explore the survival risk factors of patients.

Results

c-Met has a high expression rate in GC tissues 64.95% (63/97). The expression of c-Met was significantly different in different clinicopathological stages (p < 0.05); the high expression group also had a higher M stage and clinicopathological stage of GC. The correlation test between the c-Met H-score and CA125 was statistically significant (p = 0.004), indicating a positive correlation. Furthermore, high c-Met expression correlated with poor overall survival (OS) for 5 years (p = 0.005). It was also found that the high expression of c-Met in stage I–II patients was correlative with poor OS for 5 years (p = 0.026), while stage III–IV patients had no statistical significance (p > 0.05). Multivariate Cox regression analysis showed that c-Met might be an independent risk factor for survival 5 years after surgery.

Conclusion

This study found that the high expression of c-Met in GC tissues was associated with poor 5-year OS in GC patients and was an independent risk factor for 5-year survival after curative gastrectomy. The expression of c-Met in GC tissues was also positively correlated with preoperative serum CA125.
miR-188-3p-targeted regulation of ATG7 affects cell autophagy in patients with nonobstructive azoospermia
Authors: Wang Yuan , Tian Cheng-Cheng , Jiao Yun-Yun , Liu Min-Rui , Ma Xue-Shan , Jin Hai-Xia , Su Ying-Chun , Zhang Xiang-Yang , Niu Wen-Bin , Yao Gui-Don , Song Wen-Yan
Published: June 2022

Background

Nonobstructive azoospermia (NOA) is one of the most difficult forms of male infertility to treat, and its pathogenesis is still unclear. miRNAs can regulate autophagy by affecting their target gene expression. Our previous study found that miR-188-3p expression in NOA patients was low. There are potential binding sites between the autophagy gene ATG7 and miR-188-3p. This study aimed to verify the binding site between miR-188-3p and ATG7 and whether miR-188-3p affects autophagy and participates in NOA by regulating ATG7 to influence the autophagy marker genes LC3 and Beclin-1.

Methods

Testicular tissue from 16 NOA patients and 16 patients with normal spermatogenesis and 5 cases in each group of pathological sections were collected. High-throughput sequencing was performed to detect mRNA expression differences. Quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, immunohistochemical staining and immunofluorescence were used to detect protein localization and expression. Autophagosome changes were detected by electron microscopy. The targeting relationship between miR-188-3p and ATG7 was confirmed by a luciferase assay.

Results

ATG7 protein was localized in the cytoplasm of spermatogenic cells at all levels, and the ATG7 gene (p = 0.019) and protein (p = 0.000) were more highly expressed in the NOA group. ATG7 expression after overexpression/inhibition of miR-188-3p was significantly lower (p = 0.029)/higher (p = 0.021) than in the control group. After overexpression of miR-188-3p, the ATG7 3'UTR-WT luciferase activity was impeded (p = 0.004), while the ATG7 3'UTR-MUT luciferase activity showed no significant difference (p = 0.46). LC3 (p = 0.023) and Beclin-1 (p = 0.041) expression in the NOA group was significantly higher. LC3 and Beclin-1 gene expression after miR-188-3p overexpression/inhibition was significantly lower (p = 0.010 and 0.024, respectively) and higher (p = 0.024 and 0.049, respectively). LC3 punctate aggregation in the cytoplasm decreased after overexpression of miR-188-3p, while the LC3 punctate aggregation in the miR-188-3p inhibitor group was higher. The number of autophagosomes in the miR-188-3p mimic group was lower than the number of autophagosomes in the mimic NC group.

Conclusions

LC3 and Beclin-1 were more highly expressed in NOA testes and negatively correlated with the expression of miR-188-3p, suggesting that miR-188-3p may be involved in the process of autophagy in NOA. miR-188-3p may regulate its target gene ATG7 to participate in autophagy anDual luciferase experiment

d affect the development of NOA.
Impact of social environment on sexual behaviors of adolescent girls in 12 sub-Saharan African countries: a cross-sectional study
Authors: Darfour-Oduro Sandra A. , Grigsby-Toussaint Diana S.
Published: June 2022

Background

Early sexual debut among adolescent girls may result in teenage pregnancy and sexually transmitted diseases. In sub-Saharan Africa (SSA), pregnancy among adolescent girls may adversely impact the continuation of their education, general health status, and birth outcomes. However, few cross-national studies have examined the role that the social environment plays in adolescent girls' sexual behaviors in SSA. In this study, we explored adolescent girls' social environment and the impact on their sexual behaviors..

Methods

The country selection was based on availability of Global School-Based Student Health Survey (GSHS) national data (2003–2015). The total analytic sample was 22,067 adolescent girls from 12 countries in SSA. Descriptive statistics were generated to determine the characteristics of adolescent girls and independent samples t-test analysis were performed to determine whether there were differences between the social environment and age of sexual debut and sexual partners. Logistic regression models were used to determine the association between adolescent girls’ social environment and sexual debut.

Results

The study results showed variations across the 12 countries. Almost one in five (19.9%) adolescent girls reported to have ever engaged in sexual intercourse. Their mean age of sexual debut was 13.21 (13.04–13.37) years and mean number of sexual partners was 2.19 (2.08–2.29). We found that adolescent girls who reported not being connected with their parents were more likely to debut sex (aOR = 1.32, 95% CI, 1.14–1.53, p < 0.000). Parental monitoring was significantly associated with sexual debut but after controlling for the confounding variables (age, class grade and drug use), the association was no longer significantly positively associated. Adolescent girls who felt supported by their peers had a significantly higher number of sexual partners than those who did not feel supported by their peers.

Conclusion

The social environment of adolescent girls plays a very important role in sexual debut, age of sexual debut, and the number of sexual partners. Sexual health policies targeting adolescent girls are likely to achieve positive impacts if they focus on improving parental connectedness and peer support.
The health-related quality of life, mental health and mental illnesses of patients with inclusion body myositis (IBM): results of a mixed methods systematic review
Authors: Senn Katja C. , Gumbert Laura , Thiele Simone , Krause Sabine , Walter Maggie C. , Nagels Klaus H.
Published: June 2022

Background

Inclusion body myositis (IBM) is a rare neuromuscular disease (NMD) and effective therapies are not available. Thus, it is relevant to determine the health-related quality of life (HRQoL) in IBM patients including aspects of mental health and illnesses.

Objectives

To identify and summarize the assessment of HRQoL, mental health and illnesses in IBM, the major factors that determine and influence them as well as the respective influence of IBM in general and compared to other NMD as a systematic review.

Methods

We performed a mixed methods systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search was conducted within the databases PubMed, PsycINFO, LIVIVO and the Cochrane Database. Data were narratively summarized and categorized in the physical, psychological and social HRQoL dimensions.

Results

The systematic screening totalled 896 articles. Six studies were finally identified, comprising of 586 IBM patients. The applied patient reported outcome measures (PROMs) varied. Quantitatively, the main physical impairments (e.g. weakness, functioning, role perception) were assessed using the general population or other NMD as comparators. Results on social and psychological HRQoL were frequently inconsistent. Qualitatively, psychological and social limitations accompanied IBM related physical deteriorations.

Conclusions

A research gap exists regarding rigour determinants of HRQoL and mental illness in IBM. In-depth qualitative studies could help to prepare the ground for the assessment of long-term HRQoL data combined with appropriately focussed psychological PROMs advancing the understanding of the HRQoL in IBM throughout the course of the disease from a patient perspective.
Association between maternal breastfeeding and risk of systemic neoplasms of offspring
Authors: Gong Qin-Qin , Quan Dan-Dan , Guo Chong , Zhang Chao , Zhang Zhi-Jun
Published: June 2022

Background

Breastfeeding might prevent childhood cancer by stimulating the immune system.

Methods

The following databases, including PubMed, Embase, and Cochrane Library, were searched from inception to January 10, 2021.

Results

In dose-dependent manner, there was a statistically significant inverse association between any breastfeeding and the incidence of childhood cancer. There was no evidence that breastfeeding was inversely related to childhood cancer of the skeletal, reproductive, or sensory systems. However, breastfeeding was inversely associated with the incidence of hematological malignancies and cancers of the nervous and urinary systems. Among hematological malignancies, the relationship was significant for acute lymphocytic leukemia (ALL) and acute myeloid leukemia (AML), but not for acute non-lymphocytic leukemia (ANLL), Hodgkin’s lymphoma (HL), or non-HL.

Conclusions

The evidences demonstrated that breastfeeding have a potential protective role in preventing selective childhood cancer growth, especially for ALL, AML, cancer of nervous and urinary systems. This study recommended that breastfeeding be extended for as long as possible or maintained for at least 6 months to prevent selective childhood cancer growth.
Multiple brain abscesses in an extremely preterm infant and a 12-year follow up: a case report
Authors: Pan Shulin , Lin Su , Lin Jing , Chen Shangqin , Lin Zhenlang
Published: June 2022

Background

Brain abscesses are uncommon but life-threatening in extremely preterm (EP, Gestational Age < 28 weeks) infants. The information of long-time follow-up is rare, but very few cases presented almost intact neural function after injury.

Case presentation

We report the clinical course and the outcome of a 27-week preterm infant with multiple brain abscesses. The brain abscesses were detected by cranial magnetic resonance imaging (MRI) and were treated with surgical aspiration twice and a 7-week course of intravenous antibiotics. The patient had two episodes of seizure like activities at 8 and 11 years old respectively, whereas she had normal results of electroencephalogram (EEG). MRI showed encephalomalacia and periventricular leukomalacia. Otherwise, she had no obvious neurological deficits based on multiple physical examination and her intellectual quotient (IQ) was in normal range in the long-time follow-up.

Conclusions

Early diagnosis of brain abscesses and appropriate therapy can improve the prognosis. Furthermore, this case report provides an example of the possible neuroplasticity of brain in EP infants.
Reducing household air pollution exposure to improve early child growth and development; a randomized control trial protocol for the “Poriborton-Extension: The CHANge trial”
Authors: Raynes-Greenow Camille , Billah Sk Masum , Islam Sajia , Rokonuzzaman S. M. , Tofail Fahmida , Kirkwood Elizabeth K. , Alam Ashraful , Chartier Ryan , Ferdous Tarana E. , El Arifeen Shams , Dibley Michael J. , Homaira Nusrat , Hayes Alison , Thornburg Jonathan , Kelly Patrick
Published: June 2022

Background

Globally, household air pollution (HAP) is a leading environmental cause of morbidity and mortality. Our trial aims to assess the impact of liquefied petroleum gas (LPG) for cooking to reduce household air pollution exposure on child health outcomes, compared to usual cooking practices in Bangladesh. The primary aim is to evaluate if reduced exposure to HAP through the provision of LPG for cooking from early gestation through to age 2 improves child anthropometry, health, and neuro-cognitive developmental outcomes, compared to children exposed to emissions from usual practice.

Methods

Two-arm parallel cluster randomized controlled trial (cCRT). We will extend the intervention and follow-up of our existing “Poriborton” trial. In a subset of the original surviving participants, we will supply LPG cylinders and LPG stoves (intervention) compared to usual cooking practices and extend the follow-up to 24 months of age. The expected final sample size, for both (intervention and control) is 1854 children with follow-up to 2 years of age available for analysis.

Discussion

This trial will answer important research gaps related to HAP and child health and neuro-cognitive developmental outcomes. This evidence will help to understand the impact of a HAP intervention on child health to inform policies for the adoption of clean fuel in Bangladesh and other similar settings.

Trial registration

The Poriborton: Change trial: Household Air Pollution and Perinatal and early Neonatal mortality is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12618001214224, original trial registered on 19th July 2018, extension approved on 23rd June 2021. www.anzctr.org.au.
Reanalysis of exome negative patients with rare disease: a pragmatic workflow for diagnostic applications
Authors: Schobers Gaby , Schieving Jolanda H. , Yntema Helger G. , Pennings Maartje , Pfundt Rolph , Derks Ronny , Hofste Tom , de Wijs Ilse , Wieskamp Nienke , van den Heuvel Simone , Galbany Jordi Corominas , Gilissen Christian , Nelen Marcel , Brunner Han G. , Kleefstra Tjitske , Kamsteeg Erik-Jan , Willemsen Michèl A. A. P. , Vissers Lisenka E. L. M.
Published: June 2022

Background

Approximately two third of patients with a rare genetic disease remain undiagnosed after exome sequencing (ES). As part of our post-test counseling procedures, patients without a conclusive diagnosis are advised to recontact their referring clinician to discuss new diagnostic opportunities in due time. We performed a systematic study of genetically undiagnosed patients 5 years after their initial negative ES report to determine the efficiency of diverse reanalysis strategies.

Methods

We revisited a cohort of 150 pediatric neurology patients originally enrolled at Radboud University Medical Center, of whom 103 initially remained genetically undiagnosed. We monitored uptake of physician-initiated routine clinical and/or genetic re-evaluation (ad hoc re-evaluation) and performed systematic reanalysis, including ES-based resequencing, of all genetically undiagnosed patients (systematic re-evaluation).

Results

Ad hoc re-evaluation was initiated for 45 of 103 patients and yielded 18 diagnoses (including 1 non-genetic). Subsequent systematic re-evaluation identified another 14 diagnoses, increasing the diagnostic yield in our cohort from 31% (47/150) to 53% (79/150). New genetic diagnoses were established by reclassification of previously identified variants (10%, 3/31), reanalysis with enhanced bioinformatic pipelines (19%, 6/31), improved coverage after resequencing (29%, 9/31), and new disease-gene associations (42%, 13/31). Crucially, our systematic study also showed that 11 of the 14 further conclusive genetic diagnoses were made in patients without a genetic diagnosis that did not recontact their referring clinician.

Conclusions

We find that upon re-evaluation of undiagnosed patients, both reanalysis of existing ES data as well as resequencing strategies are needed to identify additional genetic diagnoses. Importantly, not all patients are routinely re-evaluated in clinical care, prolonging their diagnostic trajectory, unless systematic reanalysis is facilitated. We have translated our observations into considerations for systematic and ad hoc reanalysis in routine genetic care.
A proposed framework for point of care lung ultrasound by respiratory physiotherapists: scope of practice, education and governance
Authors: Smith Mike , Hayward Simon , Innes Sue
Published: June 2022

Background

Point of care ultrasound (PoCUS) has the potential to provide a step change in the management of patients across a range of healthcare settings. Increasingly, healthcare practitioners who are not medical doctors are incorporating PoCUS into their clinical practice. However, the professional, educational and regulatory environment in which this occurs is poorly developed, leaving clinicians, managers and patients at risk.

Main body

Drawing upon existing medical and non-medical literature, the authors present a proposed framework for the use of PoCUS. Throughout, mechanisms for applying the principles to other professionals and healthcare settings are signposted. Application of the framework is illustrated via one such group of healthcare practitioners and in a particular healthcare setting: respiratory physiotherapists in the UK.

In defining the point of care LUS scope of practice we detail what structures are imaged, differentials reported upon and clinical decisions informed by their imaging. This is used to outline the educational and competency requirements for respiratory physiotherapists to safely and effectively use the modality. Together, these are aligned with the regulatory (professional, legal and insurance) arrangements for this professional group in the UK.

In so doing, a comprehensive approach for respiratory physiotherapists to consolidate and expand their use of point of care LUS is presented. This provides clarity for clinicians as to the boundaries of their practice and how to train in the modality; it supports educators with the design of courses and alignment of competency assessments; it supports managers with the staffing of existing and new care pathways. Ultimately it provides greater accessibility for patients to safe and effective point of care lung ultrasound.

For clinicians who are not respiratory physiotherapists and/or are not based in the UK, the framework can be adapted to other professional groups using point of care LUS as well as other point of care ultrasound (PoCUS) applications, thereby providing a comprehensive and sustainable foundation for PoCUS consolidation and expansion.

Conclusion

This paper presents a comprehensive framework to support the use of point of care LUS by respiratory physiotherapists in the UK. Mechanisms to adapt the model to support a wide range of other PoCUS users are outlined.
Effectiveness of isometric exercises on disability and pain of cervical spondylosis: a randomized controlled trial
Authors: Sadeghi Alireza , Rostami Mina , Ameri Sahand , Karimi Moghaddam Arezoo , Karimi Moghaddam Zhaleh , Zeraatchi Alireza
Published: June 2022

Background

Neck pain and disability is a significant public health problem with only very few evidence-based treatment option. The aim of this study was to evaluate the effect of isometric exercise on pain and disability of cervical spondylosis.

Methods

Twenty four patients with cervical osteoarthritis and neck pain (22 females and 2 males; mean age, 46.70 ± 13.71 years) were recruited and randomly allocated into 2 arms: neck isometric exercises (n = 12) and conservative management without exercise (n = 12). The Neck Disability Index (NDI) and Neck Pain and Disability Scale (NPAD) were used to assess participants at baseline and after 4 weeks.

Results

Basic characteristics, NDI score and NPAD score were not significantly different between groups at baseline. The exercise arm demonstrated significantly lower scores regarding NDI (mean, 17.41 vs. 25.58; P-value = 0.035) and NPAD (mean, 25.33 vs. 66.67; P < 0.001), compared to the control arm after 4 weeks. The exercise arm also showed significant within group reduction considering NDI and NPAD scores after 4 weeks (Both, P < 0.001).

Conclusion

Our findings suggested that isometric exercises might be a beneficial treatment for improving pain and disability caused by cervical spondylosis.

Trial registration This study was registered at irct.ir (Iranian Registry of Clinical Trials) with the code IRCT20220206053950N1, 07.05.2022, retrospectively registered.
Associations between parental bonding, social isolation and loneliness: do associations persist in later life and is isolation a mediator between parental bonding and loneliness?
Authors: Burns Annette , Leavey Gerard , O’Sullivan Roger
Published: June 2022

Background

Poor parental bonding in childhood has been associated with loneliness in younger populations. Whether these associations persists into middle and older adulthood is unclear. Additionally, given the overlapping relationship between loneliness and social isolation we sought to explore the role of social isolation in any associations present i.e. are those reporting worse parental bonding lonely due to less connections or are they more likely to be lonely regardless of isolation.

Methods

Analysis of a nationally representative longitudinal sample of adults aged 50 and over from the English Longitudinal Study of Ageing was undertaken. The current analysis was based on data for core participants across waves 3[2006/7] to 8[2016/17] with missing data across waves leading to analytical samples ranging from 4384 to 5173. Multivariate adjusted multinomial regression models were used to assess associations between parental bonding [PBI], isolation [score derived from data on living alone, frequency of contact with friends, family and children, and whether or not participate in social organisations] and loneliness [R-UCLA].

Results

Parental bonding scores were associated with later life loneliness according to overall PBI score [RRR .93 95%CI .92-.95], care [RRR .90 95%CI .88-.92] and overprotection [RRR 1.11 95%CI 1.08–1.14] subscale scores as well as when separated into maternal and paternal scores, with effects larger in relation to chronic loneliness. Parental bonding scores were also associated with isolation in later life, with the exception of maternal overprotection which was non-significant. The addition of isolation to the loneliness models however had no impact on associations indicating that isolation is not a mediator of the association between parental bonding and later life loneliness.

Conclusions

Associations between parental bonding and loneliness do persist into middle and older adulthood and were in line with hypothesis stronger for more chronic loneliness. Isolation did not explain these associations and those reporting more negative parental bonds were more likely to be lonely regardless of isolation.