bluuebunny/crossref_metadata_2025 huggingface dataset:
The Pleiotropic Intricacies of Hedgehog Signaling: From Craniofacial Patterning to Carcinogenesis
Authors: Pakvasa Mikhail , Tucker Andrew B. , Shen Timothy , He Tong-Chuan , Reid Russell R.
Published: June 2021

Hedgehog signaling was discovered more than 40 years ago in experiments demonstrating that it is a fundamental mediator of limb development. Since that time, it has been shown to be important in development, homeostasis, and disease. The hedgehog pathway proceeds through a pathway highly conserved throughout animals beginning with the extracellular diffusion of hedgehog ligands, proceeding through an intracellular signaling cascade, and ending with the activation of specific target genes. A vast amount of research has been done elucidating hedgehog signaling mechanisms and regulation. This research has found a complex system of genetics and signaling that helps determine how organisms develop and function. This review provides an overview of what is known about hedgehog genetics and signaling, followed by an in-depth discussion of the role of hedgehog signaling in craniofacial development and carcinogenesis.
MiR-206 regulates the Th17/Treg ratio during osteoarthritis
Authors: Ye Xiguang , Lu Qilin , Yang Aofei , Rao Jun , Xie Wei , He Chengjian , Wang Weijun , Li Hao , Zhang Zhiwen
Published: June 2021

Background

The present study aimed to determine the functional role of miR-206 in T helper 17 (Th17)/regulatory T (Treg) cell differentiation during the development of osteoarthritis (OA).

Methods

Patients with OA and healthy controls were recruited for investigating the association between miR-206 and Th17/Treg ratio. Transfection experiments were conducted in CD4+ T cells to verify the mechanism of miR-206 on the balance of Treg/Th17. OA model was constructed to detect the clinical score, histopathological changes and Treg/Th17 ratio. OA model was induced in rats to verify the effect of miR-206 inhibition on Th17/Treg immunoregulation.

Results

High expression of miR-206 was positively correlated with peripheral Th17/Treg imbalance in patients with OA. The interactions between miR-206 and the 3′ untranslated regions (3'-UTR) of suppressor of cytokine signaling-3 (SOCS3) and fork head transcriptional factor 3 (Foxp3) were confirmed by luciferase reporter assays. MiR-206 disturbed the Th17/Treg balance by targeting SOCS3 and Foxp3. In vivo assay demonstrated that antagomiR directed against miR-206 restored Th17/Treg balance during the development of OA.

Conclusion

MiR-206 contributed to the progression of OA by modulating Th17/Treg imbalance, suggesting that miR-206 inhibition might be a promising therapeutic strategy for the treatment of OA.
Thalamo-cortical networks in subtypes of migraine with aura patients
Authors: Coppola Gianluca , Di Renzo Antonio , Tinelli Emanuele , Petolicchio Barbara , Parisi Vincenzo , Serrao Mariano , Porcaro Camillo , Fiorelli Marco , Caramia Francesca , Schoenen Jean , Di Piero Vittorio , Pierelli Francesco
Published: June 2021

Background

We searched for differences in resting-state functional connectivity (FC) between brain networks and its relationship with the microstructure of the thalamus between migraine with pure visual auras (MA), and migraine with complex neurological auras (MA+), i.e. with the addition of at least one of sensory or language symptom.

Methods

3T MRI data were obtained from 20 patients with MA and 15 with MA + and compared with those from 19 healthy controls (HCs). We collected resting state data among independent component networks. Diffusivity metrics of bilateral thalami were calculated and correlated with resting state ICs-Z-scores.

Results

As compared to HCs, both patients with MA and MA + disclosed disrupted FC between the default mode network (DMN) and the right dorsal attention system (DAS). The MA + subgroup had lower microstructural metrics than both HCs and the MA subgroup, which correlated negatively with the strength of DMN connectivity. Although the microstructural metrics of MA patients did not differ from those of HCs, these patients lacked the correlation with the strength of DAS connectivity found in HCs.

Conclusions

The present findings suggest that, as far as MRI profiles are concerned, the two clinical phenotypes of migraine with aura have both common and distinct morpho-functional features of nodes in the thalamo-cortical network.
The effect of cold waves on mortality in urban and rural areas of Madrid
Authors: López-Bueno José Antonio , Navas-Martín Miguel Ángel , Díaz Julio , Mirón Isidro Juan , Luna María Yolanda , Sánchez-Martínez Gerardo , Culqui Dante , Linares Cristina
Published: June 2021

Background

While many studies analyze the effect of extreme thermal events on health, little has been written about the effects of extreme cold on mortality. This scarcity of papers is particularly relevant when we search studies about extreme cold on the health of rural population. Therefore, we tried to analyze the effect of cold waves on urban areas and rural areas from Madrid and to test whether differentiated effects exist between both population classes. For this purpose, we analyzed data from the municipalities with over 10,000 inhabitants for the period from January 1, 2000 through December 31, 2013. Municipalities were classified as urban or rural (Eurostat), and they were grouped into similar climatological zones: Urban Metropolitan Centre (UMC), Rural Northern Mountains (RNM), Rural Centre (RC) and Southern Rural (SR). The dependent variable was the daily mortality rate due to natural causes per million inhabitants (CIE-X: A00-R99) that occurred between the months of November and March for the period. The independent variable was minimum daily temperature (ºC) (Tmin). Social and demographic contextual variables were used, including: population > age 64 (%), deprivation index and housing indicators. The analysis was carried out in three phases: (1) determination of the threshold temperature (Tthreshold) which defines the cold waves; (2) determination of the relative risk (RR) for cold waves using Poisson linear regression (GLM); and (3) using GLM of the binomial family, Odds Ratios (OR) were calculated to analyze the relationship between the frequency of the appearance of cold waves and the socioeconomic variables.

Results

The UMC zone experienced 585 extreme cold events related to attributable increases in the mortality rate. The average number of cold waves in the rural zones was 319. The primary risk factor was the percentage of population over age 64, and the primary protective factor was housing rehabilitation. As a whole, the period experienced more cold waves (1542) than heat waves (1130).

Conclusion

The UMC was more vulnerable than the rural areas. Furthermore, the results support the development of prevention policies, especially considering the fact that cold wave events were more frequent than heat waves.
SVNN: an efficient PacBio-specific pipeline for structural variations calling using neural networks
Authors: Akbarinejad Shaya , Hadadian Nejad Yousefi Mostafa , Goudarzi Maziar
Published: June 2021

Background

Once aligned, long-reads can be a useful source of information to identify the type and position of structural variations. However, due to the high sequencing error of long reads, long-read structural variation detection methods are far from precise in low-coverage cases. To be accurate, they need to use high-coverage data, which in turn, results in an extremely time-consuming pipeline, especially in the alignment phase. Therefore, it is of utmost importance to have a structural variation calling pipeline which is both fast and precise for low-coverage data.

Results

In this paper, we present SVNN, a fast yet accurate, structural variation calling pipeline for PacBio long-reads that takes raw reads as the input and detects structural variants of size larger than 50 bp. Our pipeline utilizes state-of-the-art long-read aligners, namely NGMLR and Minimap2, and structural variation callers, videlicet Sniffle and SVIM. We found that by using a neural network, we can extract features from Minimap2 output to detect a subset of reads that provide useful information for structural variation detection. By only mapping this subset with NGMLR, which is far slower than Minimap2 but better serves downstream structural variation detection, we can increase the sensitivity in an efficient way. As a result of using multiple tools intelligently, SVNN achieves up to 20 percentage points of sensitivity improvement in comparison with state-of-the-art methods and is three times faster than a naive combination of state-of-the-art tools to achieve almost the same accuracy.

Conclusion

Since prohibitive costs of using high-coverage data have impeded long-read applications, with SVNN, we provide the users with a much faster structural variation detection platform for PacBio reads with high precision and sensitivity in low-coverage scenarios.
Chromatin accessibility profiling in Neurospora crassa reveals molecular features associated with accessible and inaccessible chromatin
Authors: Ferraro Aileen R. , Ameri Abigail J. , Lu Zefu , Kamei Masayuki , Schmitz Robert J. , Lewis Zachary A.
Published: June 2021

Background

Regulation of chromatin accessibility and transcription are tightly coordinated processes. Studies in yeast and higher eukaryotes have described accessible chromatin regions, but little work has been done in filamentous fungi.

Results

Here we present a genome-scale characterization of accessible chromatin regions in Neurospora crassa, which revealed characteristic molecular features of accessible and inaccessible chromatin. We present experimental evidence of inaccessibility within heterochromatin regions in Neurospora, and we examine features of both accessible and inaccessible chromatin, including the presence of histone modifications, types of transcription, transcription factor binding, and relative nucleosome turnover rates. Chromatin accessibility is not strictly correlated with expression level. Accessible chromatin regions in the model filamentous fungus Neurospora are characterized the presence of H3K27 acetylation and commonly associated with pervasive non-coding transcription. Conversely, methylation of H3 lysine-36 catalyzed by ASH1 is correlated with inaccessible chromatin within promoter regions. Conclusions: In N. crassa, H3K27 acetylation is the most predictive histone modification for open chromatin. Conversely, our data show that H3K36 methylation is a key marker of inaccessible chromatin in gene-rich regions of the genome. Our data are consistent with an expanded role for H3K36 methylation in intergenic regions of filamentous fungi compared to the model yeasts, S. cerevisiae and S. pombe, which lack homologs of the ASH1 methyltransferase.
Prevalence and molecular characteristics of drug-resistant Mycobacterium tuberculosis in Hainan, China: from 2014 to 2019
Authors: Liu Lin , Zhao Xiujuan , Wu Xingyong , Li Sijing , Liu Biao , Rajaofera Mamy Jayne Nelly , Zeng Yingfei , Dong Sufang , Bei Zheng , Pei Hua , Xia Qianfeng
Published: June 2021

Background

The emergence of antimicrobial resistance against Mycobacterium tuberculosis (M. tuberculosis) has become the major concern in global tuberculosis control due to its limited therapy options and high mortality. However, the clinical and molecular characteristics of drug-resistant strains vary in different geographical areas. Hainan Island located in southern China, is a high drug-resistant tuberculosis burden area. This study aimed to determine the dynamic changes of drug-resistance patterns and drug-related gene mutation types of M. tuberculosis in Hainan from 2014 to 2019.

Results

A total of 1484 culture-confirmed M. tuberculosis were included in this study. It was found that the proportions of drug resistance to isoniazid and rifampin were 31.3 and 31.1% respectively. Overall the proportion of multidrug resistant M. tuberculosis was 24.9%. Multivariate logistic regression analysis showed that age and the treatment history were independent influencing factors of drug resistant tuberculosis. The proportions of drug-resistant tuberculosis in retreatment patients were considerably higher than those in new patients. The most common mutation types of isoniazid were Ser315 → Thr (66.3%), and the most common mutation types of rifampin were Ser531 → Leu (41.5%).

Conclusions

Our data suggests that the prevalence of drug resistant TB remains high in Hainan, and the risks for developing drug resistance with diversified mutation types increased significantly in retreatment patients. These results contribute to the knowledge of the prevalence of drug resistance in Hainan Province and expand the molecular characteristics of drug resistance in China simultaneously.
Expressional diversity of grapevine 3-Hydroxy-3-methylglutaryl-CoA reductase (VvHMGR) in different grapes genotypes
Authors: Zheng Ting , Guan Lubin , Yu Kun , Haider Muhammad Salman , Nasim Maazullah , Liu Zhongjie , Li Teng , Zhang Kekun , Jiu Songtao , Jia Haifeng , Fang Jinggui
Published: June 2021

Background

3-Hydroxy-3-methylglutaryl-CoA reductase (HMGR) is a key enzyme in the mevalonate (MVA) pathway, which regulates the metabolism of terpenoids in the cytoplasm and determines the type and content of downstream terpenoid metabolites.

Results

Results showed that grapevine HMGR family has three members, such asVvHMGR1,VvHMGR2, andVvHMGR3. The expression ofVvHMGRsin 'Kyoho' has tissue specificity, for example,VvHMGR1keeps a higher expression,VvHMGR2is the lowest, andVvHMGR3gradually decreases as the fruit development.VvHMGR3is closely related toCsHMGR1andGmHMGR9and has collinearity withCsHMGR2andGmHMGR4. By the prediction of interaction protein, it can interact with HMG-CoA synthase, MVA kinase, FPP/GGPP synthase, diphosphate mevalonate decarboxylase, and participates in the synthesis and metabolism of terpenoids.VvHMGR3have similar trends in expression with some of the genes of carotenoid biosynthesis and MEP pathways.VvHMGR3responds to various environmental and phytohormone stimuli, especially salt stress and ultraviolet (UV) treatment. The expression level ofVvHMGRsis diverse in grapes of different colors and aroma.VvHMGRsare significantly higher in yellow varieties than that in red varieties, whereas rose-scented varieties showed significantly higher expression than that of strawberry aroma. The expression level is highest in yellow rose-scented varieties, and the lowest in red strawberry scent varieties, especially ‘Summer Black’ and ‘Fujiminori’.

Conclusion

This study confirms the important role ofVvHMGR3in the process of grape fruit coloring and aroma formation, and provided a new idea to explain the loss of grape aroma and poor coloring during production. There may be an additive effect between color and aroma in the HMGR expression aspect.
Multimorbidity patterns in old adults and their associated multi-layered factors: a cross-sectional study
Authors: Lu Jiao , Wang Yuan , Hou Lihong , Zuo Zhenxing , Zhang Na , Wei Anle
Published: June 2021

Background

Influenced by various factors such as socio-demographic characteristics, behavioral lifestyles and socio-cultural environment, the multimorbidity patterns in old adults remain complex. This study aims to identify their characteristics and associated multi-layered factors based on health ecological model.

Methods

In 2019, we surveyed a total of 7480 participants aged 60+ by using a multi-stage random cluster sampling method in Shanxi province, China. Latent class analysis was used to discriminate the multimorbidity patterns in old adults, and hierarchical regression was performed to determine the multi-layered factors associated with their various multimorbidity patterns.

Results

The prevalence of multimorbidity was 34.70% among the old patients with chronic disease. Over half (60.59%) of the patients with multimorbidity had two co-existing chronic diseases. “Degenerative/digestive diseases”, “metabolic diseases” and “cardiovascular diseases” were three specific multimorbidity patterns. Behavioral lifestyles-layered factors had the most explanatory power for the three patterns, whose proportions of explanatory power were 54.00, 43.90 and 48.15% individually. But the contributions of other multi-layered factors were different in different patterns; balanced diet, medication adherence, the size of family and friendship network, and different types of basic medical insurance might have the opposite effect on the three multimorbidity patterns (p < 0.05).

Conclusions

In management of old patients with multimorbidity, we should prioritize both the “lifestyle change”-centered systematic management strategy and group-customized intervention programs.
Evaluation of expression of VDR-associated lncRNAs in COVID-19 patients
Authors: Taheri Mohammad , Rad Lina Moallemi , Hussen Bashdar Mahmud , Nicknafs Fwad , Sayad Arezou , Ghafouri-Fard Soudeh
Published: June 2021

Background

Coronavirus disease 2019 (COVID-19) has been shown to cause serious health problems among them is the Acute Respiratory Distress syndrome (ARDS). Vitamin D receptor (VDR) signaling possibly partakes in the pathophysiology of this devastating complication.

Methods

In the current project, we have appraised expression levels of VDR, CYP27B1 and a number of associated lncRNAs in the circulation of COVID-19 patients versus healthy subjects using real-time PCR method.

Results

Expression of SNHG6 was considerably lower in COVID-19 patients compared with control subjects (Ratio of mean expression (RME) = 0.22, P value = 7.04E-05) and in both female and male COVID-19 patients compared with sex-matched unaffected individuals (RME = 0.32, P value = 0.04 and RME = 0.16, P value = 0.000679683, respectively). However, its expression was similar among ICU-hospitalized and non-ICU patients. Similarly, expression of SNHG16 was lower in in COVID-19 patients compared with controls (RME = 0.20, P value = 5.94E-05) and in both female and male patients compared with sex-matched controls (RME = 0.32, P value = 0.04 and RME = 0.14, P value = 0.000496435, respectively) with no significant difference among ICU-hospitalized and non-ICU hospitalized patients. Expression of VDR was lower in COVID-19 patients compared with controls (RME = 0.42, P value = 0.04) and in male patients compared with male controls (RME = 0.27, P value = 0.02). Yet, expression of VDR was statistically similar between female subgroups and between ICU-hospitalized and non-ICU hospitalized patients. Expression levels CYP27B, Linc00511 and Linc00346 were similar among COVID-19 patients and healthy subjects or between their subgroups. Significant correlations have been detected between expression levels of VDR, CYP27B and SNHG6, SNHG16, Linc00511 and Linc00346 lncRNAs both among COVID-19 patients and among healthy controls with the most significant ones being SNHG6 and SNHG16 (r = 0.74, P value = 3.26e-17 and r = 0.81, P = 1.54e-22, respectively).

Conclusion

Combination of transcript levels of VDR, CYP27B and SNHG6, SNHG16, Linc00511 and Linc00346 could differentiate patients from controls with AUC = 0.76, sensitivity = 0.62 and specificity = 0.81. The current data potentiate SNHG6, SNHG16 and VDR as possible contributors in COVID-19 infection but not in the severity of ARDS.
Positive renal familial history in IgA nephropathy is associated with worse renal outcomes: a single-center longitudinal study
Authors: Sato Yoshinori , Tsukaguchi Hiroyasu , Higasa Koichiro , Kawata Naoto , Inui Kiyoko , Linh Tran Nguyen Truc , Quynh Tran Thuy Huong , Yoshihiko Inoue , Koiwa Fumihiko , Yoshimura Ashio
Published: June 2021

Background

IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Although most IgAN cases are sporadic, few show a familial aggregation. However, the prevalence and prognosis of IgAN individuals with positive familial history (FH) of renal disorders remains uncertain. To address these issues, we conducted a longitudinal observational study on a single-institution cohort of patients with biopsy-proven IgAN.

Methods

A total of 467 IgAN patients who underwent renal biopsy during 1994 to 2019 were ascertained to have positive- or negative-FH by history taking and were followed for an average of 8.9 years. We compared the clinical and pathological features of the two subgroups. The primary outcome, a composite of a hard endpoint (end-stage renal disease [ESRD]) and surrogate endpoint (a 50% or more reduction in the estimated glomerular filtration rate [eGFR] from baseline), was evaluated. To estimate the risk for progression to ESRD, a Cox proportional hazards analysis was performed for a subset of patients who underwent follow-up for > 2 years and had an eGFR > 30 mL/min/1.73 m2 at baseline (n = 389; observation, 8.7 years).

Results

Positive-FH subtype accounted for 11.6% (n = 54) of all IgAN patients. At baseline, there were no significant differences between the positive- and negative-FH subgroups regarding age, sex, comorbid disease, MEST-C score, observation period, and therapeutic interventions. However, the eGFR value at baselines was significantly lower in the positive-FH subgroup than in the negative-FH subgroup (P < 0.01). On multivariate analysis, positive-FH emerged an independent determinant of poorer renal outcomes (odds ratio, 2.31; 95% confidence interval, 1.10–4.85; P = 0.03), after adjusting for confounding factors. eGFR at follow-up was significantly lower in the positive-FH subgroup than in the negative-FH subgroup after adjustment for age and observation period.

Conclusions

Positive-FH was found in 11.6% of all IgAN patients, consistent with the incidence seen in previous literature. A significantly lower eGFR at baseline and last follow-up and unfavorable renal outcomes in the positive-FH subgroup suggest that certain genetic risk factors predisposing to renal failure may exist in a fraction of our IgAN cohort. (331 words).
The mechanisms of colorectal cancer cell mesenchymal-epithelial transition induced by hepatocyte exosome-derived miR-203a-3p
Authors: Xu Heyang , Lan Qiusheng , Huang Yongliang , Zhang Yang , Zeng Yujie , Su Pengwei , Chu Ziqiang , Lai Wei , Chu Zhonghua
Published: June 2021

Background

Liver metastasis is the most common cause of death in patients with colorectal cancer (CRC). Phosphatase of regenerating liver-3 induces CRC metastasis by epithelial-to-mesenchymal transition, which promotes CRC cell liver metastasis. Mesenchymal-to-epithelial transition (MET), the opposite of epithelial-to-mesenchymal transition, has been proposed as a mechanism for the establishment of metastatic neoplasms. However, the molecular mechanism of MET remains unclear.

Methods

Using Immunohistochemistry, western blotting, invasion assays, real-time quantitative PCR, chromatin immunoprecipitation, luciferase reporter assays, human miRNA arrays, and xenograft mouse model, we determined the role of hepatocyte exosome-derived miR-203a-3p in CRC MET.

Results

In our study, we found that miR-203a-3p derived from hepatocyte exosomes increased colorectal cancer cells E-cadherin expression, inhibited Src expression, and reduced activity. In this way miR-203a-3p induced the decreased invasion rate of CRC cells.

Coclusion

MiR-203a-3p derived from hepatocyte exosomes plays an important role of CRC cells to colonize in liver.
Prevalence and risk factors of refractive error in Qinghai, China: a cross-sectional study in Han and Tibetan adults in Xining and surrounding areas
Authors: Wang Meng , Gan Linyang , Cui Jiantao , Shan Guangliang , Chen Ting , Wang Xianghua , Wang Yuhan , Pan Li , Li Zhanquan , Cui Sen , Yang Airong , Li Wenfang , Jia Guoqiang , Han Ximing , He Huijing , Zhong Yong , Ma Jin
Published: June 2021

Background

Our study aimed to explore the prevalence and risk factors of refractive error (RE) in Han and Tibetan population aged 50–79 years in Xining and surrounding areas in Qinghai Province on Qinghai-Tibet Plateau.

Methods

As part of the China National Health Survey, our cross-sectional study compared the age-adjusted prevalence of RE in Han and Tibetan older adults aged 50–79 years in Xining and surrounding areas. A multivariate logistic regression model was used to identify risk factors for myopia and hyperopia.

Results

Among 769 Han participants and 476 Tibetan participants, the age-adjusted prevalence of myopia (spherical equivalent (SE) < − 0.5D), hyperopia (SE > + 0.5D), high myopia (SE < -6.0D) and astigmatism (cylindrical equivalent > = 0.5D) is 28.56, 22.82, 2.80, and 69.38%. Han participants have higher age-adjusted prevalence of myopia (32.93% vs 21.64%, p < 0.001), high myopia (3.93% vs 1.02%, p = 0.001) and astigmatism (72.14% vs 64.94%, p = 0.021) compared to Tibetan participants. Being Tibetan is the protective factor of myopia compared to being Han (OR 0.58, 95%CI 0.42–0.79, p < 0.001). Older age (p = 0.032), longer time length in rural area (p = 0.048), undergraduate/graduate education level (p = 0.031), lighter active level (p = 0.007) and lower BMI (p = 0.015) are risk factors for myopia. Older age (all p < 0.001) and pterygium status of the same eye (p = 0.013) also increase the hyperopia risk.

Conclusions

Our study found an overall prevalence of myopia of 28.56% in Xining and surrounding areas in adults older than 50 years. Han population has higher myopia risk than Tibetan population. More medical and social resources should be allocated to improve the vision and life quality of older adults.
Patent ductus arteriosus, systemic NT-proBNP concentrations and development of bronchopulmonary dysplasia in very preterm infants: retrospective data analysis from a randomized controlled trial
Authors: Potsiurko Solomiia , Dobryanskyy Dmytro , Sekretar Lesya
Published: June 2021

Background

Patent ductus arteriosus (PDA) is a common complication in very preterm infants. It is known that there is an association between PDA and development of bronchopulmonary dysplasia (BPD) or death before the postmenstrual age (PMA) of 36 weeks, but this association remains one of the most controversial aspects of the problem. The study aimed to evaluate the relationship between PDA, serum NT-proBNP levels at 2–3 and 8–9 days of life, and BPD/death in very preterm infants.

Methods

Data of 52 preterm infants with a gestational age < 32 weeks, chronological age < 72 h, and PDA diameter > 1.5 mm, enrolled in a randomized controlled trial, were used for the retrospective analysis. All patients underwent daily echocardiographic and two serum NT-proBNP measurements within the first 10 days after birth. Two groups of infants were formed retrospectively at PMA of 36 weeks depending on the outcome, BPD (n = 18)/death (n = 7) or survival without BPD (n = 27). Receiver operator characteristic (ROC) curve was used to evaluate the predictive performance of serum NT-proBNP levels for BPD/death occurrence.

Results

The percentage of infants who received pharmacological treatment for PDA did not differ between the groups. Based on the area under the ROC curve, serum NT-proBNP levels on the 2–3 day of life (AUC = 0.71; 95% confidence interval (CI): 0.56–0.9; p = 0.014)) and on the 8–9 day of life (AUC = 0.76; 95% CI: 0.6–0.9; p = 0.002) could reliably predict BPD/death in very preterm infants who had PDA diameter > 1.5 mm in the first 72 h of life. Hemodynamically significant PDA (hsPDA) was significantly more often detected in newborns with BPD/death, however, treatment of infants with hsPDA did not reduce the incidence of BPD/death.

Conclusions

In very preterm infants with PDA > 1.5 mm at the age of 24–48 h, serum NT-proBNP concentration could reliably predict the development of BPD or death, regardless of the persistence of PDA, with the highest diagnostic value at 8–9 days.

Trial registration

This study is registered in ClinicalTrials.gov - NCT03860428 on March 4, 2019.
Multi-purpose cash transfers and health among vulnerable Syrian refugees in Lebanon: a prospective cohort study
Authors: Lyles Emily , Arhem Jakob , El Khoury Ghada , Trujillo Antonio , Spiegel Paul , Burton Ann , Doocy Shannon
Published: June 2021

Background

Multipurpose cash transfers (MPCs) are used on a widespread basis in the Syrian refugee response; however, there is little to no evidence as to how they affect health in humanitarian crises.

Methods

A prospective cohort study was conducted from May 2018 through July 2019 to evaluate the impact of MPCs on health care-seeking and expenditures for child, adult acute, and adult chronic illness by Syrian refugees in Lebanon. Households receiving MPCs from UNHCR were compared to control households not receiving UNHCR MPCs.

Results

Care-seeking for childhood illness was consistently high in both MPC and non-MPC households. An increased proportion of households did not receive all recommended care due to cost; this increase was 19.3% greater among MPC recipients than controls (P = 0.002). Increases in child hospitalizations were significantly smaller among MPC recipients than controls (DiD -6.1%; P = 0.037).

For adult acute illnesses, care-seeking increased among MPC recipients but decreased in controls (adjusted DiD 11.3%; P = 0.057); differences in change for other utilization outcomes were not significant. The adjusted difference in change in the proportion of MPC households not receiving recommended chronic illness care due to cost compared to controls was − 28.2% (P = 0.073). Access to medication for adult chronic illness also marginally significantly improved for MPC households relative to controls. The proportion of MPC recipients reporting expenses for the most recent child and adult acute illness increased significantly, as did the [log] total visit cost.

Both MPC and control households reported significant increases in borrowing to pay for health expenses over the year study period, but differences in change in borrowing or asset sales were not significant, indicating that MPC was not protective against for household financial risks associated with health.

Conclusions

While MPC may have shown some positive effects, findings were mixed and MPC appears insufficient on its own to address health utilization and expenditures. A broader strategy addressing Syrian refugee health in Lebanon is needed of which MPC should be incorporated, with additional support such as additional conditional cash transfers for health.
Caregivers’ perception of the caring challenges in coronavirus crisis (COVID-19): a qualitative study
Authors: Mohammadi Fateme , Farjam Mojtaba , Gholampour Yousef , Sohrabpour Mojtaba , Oshvandi Khodayar , Bijani Mostafa
Published: June 2021

Background

The nurses act as the guardians of people’s health by preventing, controlling, and curing emerging diseases, including coronavirus, a highly infectious and contagious disease which has presented the caregivers in the Iranian healthcare system with many clinical challenges. In view of lack of research on the clinical challenges which arise during health crises, emerging diseases included, there is need for further investigation of those clinical challenges and dilemmas. The aim in present study was to describe the caregivers’ experiences of the caring challenges in patients with coronavirus (COVID-19).

Methods

The present study is a qualitative work with a phenomenological-descriptive design. Data were collected via semi-structured, in-depth, individual interviews. The collected data were analyzed according to Colaizzi’s method. The participants were 23 members of the medical staff responsible for coronavirus patients in Iran who met the inclusion criteria. The participants were selected via purposeful sampling which was continued to the point of data saturation.

Results

The results yielded 3 main themes “psychological tension”, “inefficient management”, and “contextual factors” with 11 categories.

Conclusion

In dealing with coronavirus patients and providing quality care to them, nurses face various clinical challenges which affect their performance. Administrators must, alongside giving instructions to people on how to prevent the coronavirus disease and taking effective safety measures, make sure that clinical centers are managed efficiently in order for nurses to fulfill their caring objectives satisfactorily.
Utilization of eye health services and diabetic retinopathy: a cross-sectional study among persons living with diabetes visiting a tertiary eye care facility in Ghana
Authors: Akrofi Bridgid , Tetteh John , Amissah-Arthur Kwesi N. , Buxton Eileen N.A. , Yawson Alfred
Published: June 2021

Background

There have been a major advance made in screening, early diagnosis, and prompt treatment of Diabetic Retinopathy among Person living with diabetes (PLWD). However, screening services remain a challenge in Low-Middle-Income-Countries where access to eye care professionals is inadequate. This study assesses the utilization of Eye Health Service prevalence (UEHS) among PLWD and associated factors and further quantifies its association with Non-Proliferative Diabetic Retinopathy (NPDR).

Methods

A cross-sectional study design with a random sample of 360 PLWD was conducted at Korle-Bu Teaching Hospital, a National Referral Centre in Ghana from May to July 2019. UEHS and DR were the study outcomes. We adopted Poisson and Probit regression analysis to assess factors associated with UEHS over the past year. We employed pairwise and phi correlation (fourfold correlational analysis) to assess the relationship between UEHS and DR (ordinal and binary respectively). Ordered Logistic and Poisson regression were applied to assess the association between the UEHS and DR. Stata 16.1 was used to perform the analyses and a p-value ≤ 0.05 was deemed significant.

Results

The prevalence of UEHS over the past year and DR was 21.7 %(95 %CI = 17.7–26.2) and 65.0 %(95 %CI = 59.9–69.8 respectively. The prevalence of severe NPDR with Clinically Significant Macular Edema (CSME) was 23.9 %(19.8–28.6). Type of diabetes, increasing age, educational level, mode of payment for healthcare services, marital status, years since diagnosis, and current blood glucose significantly influenced UEHS. There was a negative relationship between DR and UEHS (Pairwise and φ correlation were − 20 and − 15 respectively; p < 0.001). Non-UEHS among PLWD doubles the likelihood of experiencing severe NPDR with CSME compared with UEHS among PLWD [aOR(95 %CI) = 2.05(1.03–4.08)]. Meanwhile, the prevalence of DR among patients per non-UEHS was insignificantly higher [12 %; aPR(95 %CI) = 0.89–1.41)] compared with patients who utilized eye care health service.

Conclusions

Most of the PLWD did not utilize the eye health service even once in a year and that was highly influenced by type of diabetes and increasing age. Type 2 diabetes patients and middle age decreased the likelihood of UEHS. There was a negative relationship between DR and UEHS among PLWD and this doubled the likelihood of experiencing severe NPDR with CSME. Structured health education and screening interventions are key to improving UEHS.
Screening the genome for HCC-specific CpG methylation signatures as biomarkers for diagnosis and prognosis evaluation
Authors: Zhang Rui-kun , Liu Jia-lin
Published: June 2021

Background

Hepatocellular carcinoma (HCC) is one of the most common and invasive malignant tumors in the world. The change in DNA methylation is a key event in HCC.

Methods

Methylation datasets for HCC and 17 other types of cancer were downloaded from The Cancer Genome Atlas (TCGA). The CpG sites with large differences in methylation between tumor tissues and paracancerous tissues were identified. We used the HCC methylation dataset downloaded from the TCGA as the training set and removed the overlapping sites among all cancer datasets to ensure that only CpG sites specific to HCC remained. Logistic regression analysis was performed to select specific biomarkers that can be used to diagnose HCC, and two datasets—GSE157341 and GSE54503—downloaded from GEO as validation sets were used to validate our model. We also used a Cox regression model to select CpG sites related to patient prognosis.

Results

We identified 6 HCC-specific methylated CpG sites as biomarkers for HCC diagnosis. In the training set, the area under the receiver operating characteristic (ROC) curve (AUC) for the model containing all these sites was 0.971. The AUCs were 0.8802 and 0.9711 for the two validation sets from the GEO database. In addition, 3 other CpG sites were analyzed and used to create a risk scoring model for patient prognosis and survival prediction.

Conclusions

Through the analysis of HCC methylation datasets from the TCGA and Gene Expression Omnibus (GEO) databases, potential biomarkers for HCC diagnosis and prognosis evaluation were ascertained.
RSF1 in cancer: interactions and functions
Authors: Cai Guiyang , Yang Qing , Sun Wei
Published: June 2021

RSF1, remodelling and spacing factor 1, is an important interphase centromere protein and is overexpressed in many types of cancers and correlated with poor overall survival. RSF1 has functions mainly in maintaining chromosome stability, facilitating DNA repair, maintaining the protein homeostasis of RSF1 and suppressing the transcription of some oncogenes when RSF1 protein is expressed at an optimal level; however, RSF1 overexpression facilitates drug resistance and cell cycle checkpoint inhibition to prompt cancer proliferation and survival. The RSF1 expression level and gene background are crucial for RSF1 functions, which may explain why RSF1 has different functions in different cancer types. This review summarizes the functional domains of RSF1, the overexpression status of RSF1 and SNF2H in cancer based on the TCGA and GTEX databases, the cancer-related functions of RSF1 in interacting with H2Aub, HDAC1, CENP-A, PLK1, ATM, CENP-S, SNF2H, HBX, BubR1, cyclin E1, CBP and NF-κB and the potential clinical value of RSF1, which will lay a theoretical foundation for the structural biology study of RSF1 and application of RSF1 inhibitors, truncated RSF1 proteins and SNF2H inhibitors in the treatment of RSF1-overexpressing tumours.
Inequities in the delivery of mental health care: a grounded theory study of the policy context of primary care
Authors: Ashcroft Rachelle , Menear Matthew , Silveira Jose , Dahrouge Simone , Emode Monica , Booton Jocelyn , McKenzie Kwame
Published: June 2021

Background

Strengthening capacity for mental health in primary care improves health outcomes by providing timely access to coordinated and integrated mental health care. The successful integration of mental health in primary care is highly dependent on the foundation of the surrounding policy context. In Ontario, Canada, policy reforms in the early 2000’s led to the implementation of a new interprofessional team-model of primary care called Family Health Teams. It is unclear the extent to which the policy context in Ontario influenced the integration of mental health care in Family Health Teams emerging from this period of policy reform. The research question guiding this study was: what were key features of Ontario’s policy context that influenced FHTs capacity to provide mental health services for mood and anxiety disorders?

Methods

A qualitative study informed by constructivist grounded theory. Individual interviews were conducted with executive directors, family physicians, nurse practitioners, nurses, and the range of professionals who provide mental health services in interprofessional primary care teams; community mental health providers; and provincial policy and decision makers. We used an inductive approach to data analysis. The electronic data management programme NVivo11 helped organise the data analysis process.

Results

We conducted 96 interviews with 82 participants. With respect to the contextual factors considered to be important features of Ontario’s policy context that influenced primary care teams’ capacity to provide mental health services, we identified four key themes: i) lack of strategic direction for mental health, ii) inadequate resourcing for mental health care, iii) rivalry and envy, and, iv) variations across primary care models.

Conclusions

As the first point of contact for individuals experiencing mental health difficulties, primary care plays an important role in addressing population mental health care needs. In Ontario, the successful integration of mental health in primary care has been hindered by the lack of strategic direction, and inconsistent resourcing for mental health care. Achieving health equity may be stunted by the structural variations for mental health care across Family Health Teams and across primary care models in Ontario.
Evaluating the impact of social deprivation on Press Ganey® Outpatient Medical Practice Survey Scores
Authors: Stephens Andrew R. , Potter Jared W. , Tyser Andrew R. , Kazmers Nikolas H.
Published: June 2021

Background

Social deprivation has been shown to affect access to health care services, and influences outcomes for a variety of physical and psychological conditions. However, the impact on patient satisfaction remains less clear. The objective of this study was to determine if social deprivation is an independent predictor of patient satisfaction, as measured by the Press Ganey® Outpatient Medical Practice Survey (PGOMPS).

Methods

We retrospectively reviewed unique new adult patient (≥ 18 years of age) seen at a tertiary academic hospital and rural/urban outreach hospitals/clinics between January 2014 and December 2017. Satisfaction was defined a priori as achieving a score above the 33rd percentile. The 2015 Area Deprivation Index (ADI) was used to determine social deprivation (lower score signifies less social deprivation). Univariate and multivariable binary logistic regression were used to determine the impact of ADI on PGOMPS total and provider sub-scores while controlling for variables previously shown to impact scores (wait time, patient age, sex, race, specialty type, provider type, and insurance status).

Results

Univariate analysis of PGOMPS total scores revealed a 4% decrease in odds of patient satisfaction per decile increase in ADI (p < 0.001). Patients within the most deprived quartile were significantly less likely to report satisfaction compared to the least deprived quartile (OR 0.79, p < 0.001). Multivariable analysis revealed that the odds of achieving satisfaction decreased 2% for each decile increase in ADI on the Total Score (p < 0.001), independent of other variables previously shown to impact scores. For PGOMPS Provider Sub-Score, univariate analysis showed that patients in the lowest ADI quartile were significantly less likely be satisfied, as compared to the least deprived quartile (OR 0.77; 95% CI 0.70–0.86; p < 0.001). A 5% decrease in a patient being satisfied was observed for each decile increase in ADI (OR 0.95; 95% CI 0.94–0.96; p < 0.001).

Conclusions

Social deprivation was an independent predictor of outpatient visit dissatisfaction, as measured by the Press Ganey® Outpatient Medical Practice Survey. These results necessitate consideration when developing health care delivery policies that serve to minimize inequalities between patients of differing socioeconomic groups.
Clinicians’ perspectives on quality: do they match accreditation standards?
Authors: Akdemir Nesibe , Malik Romana , Walters Theanne , Hamstra Stanley , Scheele Fedde
Published: June 2021

Background

Quality of training is determined through programs’ compliance with accreditation standards, often set for a number of years. However, perspectives on quality of training within these standards may differ from the clinicians’ perspectives on quality of training. Knowledge on how standards relate to clinicians’ perspectives on quality of training is currently lacking yet is expected to lead to improved accreditation design.

Methods

This qualitative study design was based on a case-study research approach. We analyzed accreditation standards and conducted 29 interviews with accreditors, clinical supervisors and trainees across Australia and the Netherlands about the quality and accreditation of specialist medical training programs. The perspectives were coded and either if applicable compared to national accreditation standards of both jurisdictions, or thematized to the way stakeholders encounter accreditation standards in practice.

Results

There were two evident matches and four mismatches between the perspectives of clinicians and the accreditation standards. The matches are: (1) accreditation is necessary (2) trainees are the best source for quality measures. The mismatches are: (3) fundamental training aspects that accreditation standards do not capture: the balance between training and service provision, and trainee empowerment (4) using standards lack dynamism and (5) quality improvement; driven by standards or intrinsic motivation of healthcare professionals.

Conclusion

In our Australian and Dutch health education cases accreditation is an accepted phenomenon which may be improved by trainee empowerment, a dynamic updating process of standards and by flexibility in its use.
Understanding the complexity of population health interventions: assessing intervention system theory (ISyT)
Authors: Cambon Linda , Alla François
Published: June 2021

Given their inherent complexity, we need a better understanding of what is happening inside the “black box” of population health interventions. The theory-driven intervention/evaluation paradigm is one approach to addressing this question. However, barriers related to semantic or practical issues stand in the way of its complete integration into evaluation designs. In this paper, we attempt to clarify how various theories, models and frameworks can contribute to developing a context-dependent theory, helping us to understand the black box of population health interventions and to acknowledge their complexity. To achieve this goal, we clarify what could be referred to as “theory” in the theory-driven evaluation of the interventional system, distinguishing it from other models, frameworks and classical theories. In order to evaluate the interventional system with a theory-driven paradigm, we put forward the concept of interventional system theory (ISyT), which combines a causal theory and an action model. We suggest that an ISyT could guide evaluation processes, whatever evaluation design is applied, and illustrate this alternative method through different examples of studies. We believe that such a clarification can help to promote the use of theories in complex intervention evaluations, and to identify ways of considering the transferability and scalability of interventions.
Brain endothelial LRP1 maintains blood–brain barrier integrity
Authors: Storck Steffen E. , Kurtyka Magdalena , Pietrzik Claus U.
Published: June 2021

The entry of blood-borne molecules into the brain is restricted by the blood–brain barrier (BBB). Various physical, transport and immune properties tightly regulate molecule movement between the blood and the brain to maintain brain homeostasis. A recent study utilizing a pan-endothelial, constitutive Tie2-Cre showed that paracellular passage of blood proteins into the brain is governed by endocytic and cell signaling protein low-density lipoprotein receptor–related protein 1 (LRP1). Taking advantage of conditional Slco1c1-CreERT2 specific to CNS endothelial cells and choroid plexus epithelial cells we now supplement previous results and show that brain endothelial Lrp1 ablation results in protease-mediated tight junction degradation, P-glycoprotein (P-gp) reduction and a loss of BBB integrity.