bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of educational intervention based on the theory of planned behavior on improving physical and nutrition status of obese and overweight women
Authors: Khani Jeihooni Ali , Layeghiasl Mehdi , Yari Asiyeh , Rakhshani Tayebeh
Published: January 2022

Background

Regarding the high rate of obesity and overweight among women, develop a comprehensive and effective program it seems necessary to improve their nutritional behaviors and physical activity. This study aims to survey the effect of educational intervention based on the theory of planned behavior (TPB) on improving physical and nutritional activities of obese and overweight women.

Methods

This experimental study was performed on 400 obese and overweight women over the age of 20. The sampling method was A simple random sampling. The data collection was valid and reliable self-reports measure, questionnaires. This tools was including demographic information, questionnaire based on the constructs of the theory of planned behavior, physical activity performance questionnaire and nutritional performance questionnaire that individuals completed before and 6 months after the educational intervention. The training intervention for the experimental group consisted of 12 sessions of 50–55 min. Data analyzed by SPSS22 and by using chi-square test, independent t-test and paired t-test.

Results

Findings showed that before the educational intervention, was no significant difference between the experimental and control groups in terms of education, household monthly income, occupation, mean age, marital status, awareness, attitude, perceived behavioral control, subjective norms, physical activity and nutritional behavioral intentions, and physical activity and nutritional performance, weight and BMI. However, six months after the training intervention, there was a significant increase in each of the TPB contracts, weight and BMI in the experimental group, while no significant difference was observed in the control group. The meaningful level was considered 0.05.

Conclusion

Our findings partially support of applying theory of planned behavior in reducing the weight, BMI and improved nutritional performance and physical activity of the study subjects. TPB could be an important strategy for effective future educational interventions.
Elagolix treatment in women with heavy menstrual bleeding associated with uterine fibroid: a systematic review and meta-analysis
Authors: Muhammad Juliawati , Yusof Yusnita , Ahmad Imran , Norhayati Mohd Noor
Published: January 2022

Background

Elagolix is effective and safe for treating menorrhagia in women with uterine fibroid. However, it is reported to be associated with hypoestrogenism that can be alleviated by adding estradiol/norethindrone acetate. This systematic review and meta-analysis aimed to determine the effectiveness of elagolix treatment in women with heavy menstrual bleeding associated with uterine fibroid by comparing: elagolix versus placebo and elagolix versus estradiol/norethindrone acetate.

Methodology

The Cochrane Central Register of Controlled Trials (CENTRAL 2021, Issue 3 of 12), MEDLINE databases (1980 to December week 1, 2020), and trial registries for relevant randomized clinical trials were used. All randomized clinical trials were reviewed and evaluated. Random effects models were used to estimate the dichotomous outcomes and mean differences with 95% confidence intervals. Data for risk of bias, heterogeneity, sensitivity, reporting bias and quality of evidence were assessed.

Results

Four randomized controlled trials with 1949 premenopausal women from 323 locations were included. Elagolix improved menstrual blood loss of less than 80 ml (RR 4.81, 95% CI 2.45 to 9.45; four trials, 869 participants; moderate quality evidence) or more than 50% reduction from baseline (RR 4.87, 95% CI 2.55 to 9.31; four trials, 869 participants; moderate quality evidence) compared to placebo. There was no difference in menstrual blood loss of less than 80 ml (RR 1.08, 95% CI 1.00 to 1.16; five trials, 1365 participants; moderate quality evidence) or more than 50% reduction from baseline between the elagolix (RR 1.08, 95% CI 1.01 to 1.15; five trials, 1365 participants; high quality evidence) and elagolix with estradiol/norethindrone acetate. In both comparisons, elagolix has reduced the mean percentage change in uterine and fibroid volume, improved symptoms, and health-related quality of life. More patients had hot flush, and bone mineral density loss in the elagolix treatment compared to both placebo and elagolix with estradiol/norethindrone acetate.

Conclusions

Elagolix appeared to be effective in reducing heavy menstrual bleeding caused by uterine fibroid and combination with estradiol/norethindrone acetate was able to alleviate the hypoestrogenism side effects in premenopausal women.

Review registration

PROSPERO CDR 42021233898.
User testing of a Scottish Intercollegiate Guideline Network public guideline for the parents of children with autism
Authors: Fearns Naomi , Walker Laura , Graham Karen , Gibb Norman , Service Duncan
Published: January 2022

Background

The Scottish Intercollegiate Guidelines Network (SIGN) is the leading national clinical guideline producer in Scotland. Improved design and dissemination of guidelines produced for the public can empower people to take an active role in self-management and shared decision-making. The public version of the guideline examined covered getting assessed and diagnosed with autism, and approaches that can help. The aim of this study was to test a public version of a guideline for the parents of children and young people with autism, implement improvements, and identify what works in making it usable and accessible.

Methods

We recruited mothers from across Scotland. User testing involved formal ‘think aloud’ semi-structured interviews that guided users through the booklet. Interviews took place individually and were recorded and transcribed. Key findings were identified and themed using the honeycomb user experience model.

Results

Fourteen user-testing interviews were conducted. Facilitators for usability and desirability of the guideline included the chunking of text, consistent use of colour and boxes to highlight important information. Simple language, written in a tone of partnership, helped to engage mothers. Value arose from the guidelines ability to explain the process of diagnosis and make mothers feel empowered in their relationships with healthcare professionals. There was a lack of consensus on the usefulness of rating the strength of evidence and recommendations.

Conclusion

There was a marked similarity between what was important to the mothers and what has been found to be important to other groups. The involvement of service users and carers in the guidelines development was key to its credibility. One size does not fit all in presenting evidence-based recommendations to the public and it is a challenge to provide sufficient information while avoiding information overload. Recommendations and evidence levels are suitable for use in public versions, but these should be kept as simple as possible.
Comparison of outcomes between medical and surgical treatment in dogs with prostatic adenocarcinoma: a retrospective study
Authors: Iizuka Keigo , Ishigaki Kumiko , Seki Mamiko , Nagumo Takahiro , Tamura Kei , Sakurai Naoki , Terai Kazuyuki , Asano Kazushi
Published: January 2022

Background

Prostatic cancer is uncommon in dogs. Dogs with prostatic carcinoma have been reported to have a poor prognosis. Information regarding prognosis with various surgery options as well as prognosis with surgical vs. medical treatment is lacking. This retrospective study compares the outcomes of medical management to surgical treatment in dogs with prostatic adenocarcinoma and assesses the surgical outcomes of patients who underwent total prostatectomy (TP) and prostatocystectomy (TPC). The medical records of 41 dogs with prostatic adenocarcinoma, between February 2008 and June 2019, were reviewed for information on signalment, clinical signs in the initial evaluation, preoperative diagnostic imaging findings, treatment type (non-surgical or surgical), surgery type, postoperative complications, adjunctive medical therapy, and survival time. The dogs were divided into non-surgical (n = 12) or surgical (n = 29) groups. The surgical group was subdivided into the TP (n = 20) and TPC (n = 9) subgroups.

Results

Age was not significantly different between the surgical (median 13.1 years [8.4–15.4] years) and the non-surgical groups (median 10.8 [7.7–15.3] years). Body weight (BW) was also not significantly different between the surgical (median 6.8 kg [2.4–34.5 kg]) and non-surgical groups (median 6.4 kg [3.7–9.12 kg]). The overall median survival time (MST) from the initial evaluation was significantly longer in the surgical than in the non-surgical group (337 vs. 90.5 days). The postoperative MST was significantly longer in the TP group than in the TPC subgroup (510 vs. 83 days). As TPC was performed in cases of tumor progression, its postoperative complications were severe, resulting in a shorter MST. Ten (50%) and 6 patients (30%) in the TP subgroup postoperatively showed mild and severe urinary incontinence, respectively, whereas all patients in TPC subgroup did show severe incontinence.

Conclusion

Results of the study suggest that surgical treatment of prostatic carcinoma results in longer survival times over medical management alone. In particular, TP might be recommended for improving survival time and quality of life in canine prostatic adenocarcinoma that does not infiltrate the bladder. Early detection is key for a survival advantage with surgical treatment.
Effects of rumen-protected creatine pyruvate on blood biochemical parameters and rumen fluid characteristics in transported beef cattle
Authors: Mao Kang , Lu Guwei , Li Yanjiao , Zang Yitian , Zhao Xianghui , Qiu Qinghua , Qu Mingren , Ouyang Kehui
Published: January 2022

Background

The fasting and stress associated with road transportation contributes to a lack of energy and a decline in the immune system of beef cattle. Therefore, it is essential for beef cattle to enhance energy reserves before transportation. Creatine pyruvate (CrPyr) is a new multifunctional nutrient that can provide both pyruvate and creatine, which are two intermediate products of energy metabolism. To investigate the effects of transport and rumen-protected (RP)-CrPyr on the blood biochemical parameters and rumen fluid characteristics of beef cattle, twenty male Simmental crossbred cattle (659 ± 16 kg) aged 18 months were randomly allocated to four groups (n = 5) using a 2 × 2 factorial arrangement with two RP-CrPyr supplemental levels (0 or 140 g/d) and two transport treatments (5 min or 12 h): T_CrPyr140, T_CrPyr0, NT_CrPyr140, and NT_CrPyr0. After feeding for 30 days, three cattle per treatment were slaughtered.

Results

Compared with nontransport, transport decreased the total antioxidant capacity, catalase activity, contents of IgA, interferon γ, interleukin-1β (IL-1β), and IL-6 in serum, and the amounts of total volatile fatty acids (TVFA), acetate, and butyrate in rumen (P < 0.05); increased the serum lipopolysaccharide (LPS) level, contents of rumen LPS and ammonia nitrogen (P < 0.05). RP-CrPyr supplementation decreased the levels of cortisol and LPS in serum and the butyrate concentration in the rumen of beef cattle compared with those in the unsupplemented groups (P < 0.05). RP-CrPyr and transport interaction had a significant effect on the contents of serum tumour necrosis factor-α, IL-6, LPS, ruminal pH, acetate content, and acetate/propionate (P < 0.05). In terms of ruminal bacterial composition, group T_CrPyr0 increased the Prevotella genus abundance compared with group NT_CrPyr0 (P < 0.05), while group T_CrPyr140 increased Firmicutes phylum abundance and decreased Bacteroidetes phylum and genus Prevotella abundance compared with group T_CrPyr0 (P < 0.05). Moreover, Bacteroidetes was positively correlated with serum LPS.

Conclusions

These results indicated that dietary supplementation with RP-CrPyr might be beneficial to alleviate transport stress by decreasing serum cortisol and LPS levels and promoting the restoration of the rumen natural flora.
Relationship between gut microbiota and lung function decline in patients with chronic obstructive pulmonary disease: a 1-year follow-up study
Authors: Chiu Yu-Chi , Lee Shih-Wei , Liu Chi-Wei , Lan Tzuo-Yun , Wu Lawrence Shih-Hsin
Published: January 2022

Objective

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease characterized by a persistent limitation in airflow. Gut microbiota is closely correlated with lung inflammation. However, gut microbiota has not been studied in patients with declining lung function, due to chronic lung disease progression.

Subjects and methods

Stool samples were obtained from 55 patients with COPD that were in stable condition at enrolment (stage 1) and at a 1-year follow-up (stage 2). After extracting stool DNA, we performed next generation sequencing to analyse the distribution of gut microbiota.

Results

Patients were divided to control and declining lung function groups, based on whether the rate of forced expiratory volume in 1 s (FEV1) had declined over time. An alpha diversity analysis of initial and follow-up stool samples showed a significant difference in the community richness of microbiota in the declining function group, but not in the control group. At the phylum level, Bacteroidetes was more abundant in the control group and Firmicutes was more abundant in the declining function group. The Alloprevotella genus was more abundant in the control group than in the declining function group. At 1-year follow-up, the mean proportions of Acinetobacter and Stenotrophomonas significantly increased in the control and declining function groups, respectively.

Conclusion

Some community shifts in gut microbiota were associated with lung function decline in COPD patients under regular treatment. Future studies should investigate the mechanism underlying alterations in lung function, due to changes in gut bacterial communities, in COPD.
Escherichia coli coculture for de novo production of esters derived of methyl-branched alcohols and multi-methyl branched fatty acids
Authors: Bracalente Fernando , Sabatini Martín , Arabolaza Ana , Gramajo Hugo
Published: January 2022

Background

A broad diversity of natural and non-natural esters have now been made in bacteria, and in other microorganisms, as a result of original metabolic engineering approaches. However, the fact that the properties of these molecules, and therefore their applications, are largely defined by the structural features of the fatty acid and alcohol moieties, has driven a persistent interest in generating novel structures of these chemicals.

Results

In this research, we engineered Escherichia coli to synthesize de novo esters composed of multi-methyl-branched-chain fatty acids and short branched-chain alcohols (BCA), from glucose and propionate. A coculture engineering strategy was developed to avoid metabolic burden generated by the reconstitution of long heterologous biosynthetic pathways. The cocultures were composed of two independently optimized E. coli strains, one dedicated to efficiently achieve the biosynthesis and release of the BCA, and the other to synthesize the multi methyl-branched fatty acid and the corresponding multi-methyl-branched esters (MBE) as the final products. Response surface methodology, a cost-efficient multivariate statistical technique, was used to empirical model the BCA-derived MBE production landscape of the coculture and to optimize its productivity. Compared with the monoculture strategy, the utilization of the designed coculture improved the BCA-derived MBE production in 45%. Finally, the coculture was scaled up in a high-cell density fed-batch fermentation in a 2 L bioreactor by fine-tuning the inoculation ratio between the two engineered E. coli strains.

Conclusion

Previous work revealed that esters containing multiple methyl branches in their molecule present favorable physicochemical properties which are superior to those of linear esters. Here, we have successfully engineered an E. coli strain to broaden the diversity of these molecules by incorporating methyl branches also in the alcohol moiety. The limited production of these esters by a monoculture was considerable improved by a design of a coculture system and its optimization using response surface methodology. The possibility to scale-up this process was confirmed in high-cell density fed-batch fermentations.
Recombinant production of the lantibiotic nisin using Corynebacterium glutamicum in a two-step process
Authors: Weixler Dominik , Berghoff Max , Ovchinnikov Kirill V. , Reich Sebastian , Goldbeck Oliver , Seibold Gerd M. , Wittmann Christoph , Bar Nadav S. , Eikmanns Bernhard J. , Diep Dzung B. , Riedel Christian U.
Published: January 2022

Background

The bacteriocin nisin is naturally produced by Lactococcus lactis as an inactive prepeptide that is modified posttranslationally resulting in five (methyl-)lanthionine rings characteristic for class Ia bacteriocins. Export and proteolytic cleavage of the leader peptide results in release of active nisin. By targeting the universal peptidoglycan precursor lipid II, nisin has a broad target spectrum including important human pathogens such as Listeria monocytogenes and methicillin-resistant Staphylococcus aureus strains. Industrial nisin production is currently performed using natural producer strains resulting in rather low product purity and limiting its application to preservation of dairy food products.

Results

We established heterologous nisin production using the biotechnological workhorse organism Corynebacterium glutamicum in a two-step process. We demonstrate successful biosynthesis and export of fully modified prenisin and its activation to mature nisin by a purified, soluble variant of the nisin protease NisP (sNisP) produced in Escherichia coli. Active nisin was detected by a L. lactis sensor strain with strictly nisin-dependent expression of the fluorescent protein mCherry. Following activation by sNisP, supernatants of the recombinant C. glutamicum producer strain cultivated in standard batch fermentations contained at least 1.25 mg/l active nisin.

Conclusions

We demonstrate successful implementation of a two-step process for recombinant production of active nisin with C. glutamicum. This extends the spectrum of bioactive compounds that may be produced using C. glutamicum to a bacteriocin harboring complex posttranslational modifications. Our results provide a basis for further studies to optimize product yields, transfer production to sustainable substrates and purification of pharmaceutical grade nisin.
Application of artificial intelligence in a real-world research for predicting the risk of liver metastasis in T1 colorectal cancer
Authors: Han Tenghui , Zhu Jun , Chen Xiaoping , Chen Rujie , Jiang Yu , Wang Shuai , Xu Dong , Shen Gang , Zheng Jianyong , Xu Chunsheng
Published: January 2022

Background

Liver is the most common metastatic site of colorectal cancer (CRC) and liver metastasis (LM) determines subsequent treatment as well as prognosis of patients, especially in T1 patients. T1 CRC patients with LM are recommended to adopt surgery and systematic treatments rather than endoscopic therapy alone. Nevertheless, there is still no effective model to predict the risk of LM in T1 CRC patients. Hence, we aim to construct an accurate predictive model and an easy-to-use tool clinically.

Methods

We integrated two independent CRC cohorts from Surveillance Epidemiology and End Results database (SEER, training dataset) and Xijing hospital (testing dataset). Artificial intelligence (AI) and machine learning (ML) methods were adopted to establish the predictive model.

Results

A total of 16,785 and 326 T1 CRC patients from SEER database and Xijing hospital were incorporated respectively into the study. Every single ML model demonstrated great predictive capability, with an area under the curve (AUC) close to 0.95 and a stacking bagging model displaying the best performance (AUC = 0.9631). Expectedly, the stacking model exhibited a favorable discriminative ability and precisely screened out all eight LM cases from 326 T1 patients in the outer validation cohort. In the subgroup analysis, the stacking model also demonstrated a splendid predictive ability for patients with tumor size ranging from one to50mm (AUC = 0.956).

Conclusion

We successfully established an innovative and convenient AI model for predicting LM in T1 CRC patients, which was further verified in the external dataset. Ultimately, we designed a novel and easy-to-use decision tree, which only incorporated four fundamental parameters and could be successfully applied in clinical practice.
Development and validation of a novel 3-gene prognostic model for pancreatic adenocarcinoma based on ferroptosis-related genes
Authors: Yang Jihua , Wei XiaoHong , Hu Fang , Dong Wei , Sun Liao
Published: January 2022

Background

Molecular markers play an important role in predicting clinical outcomes in pancreatic adenocarcinoma (PAAD) patients. Analysis of the ferroptosis-related genes may provide novel potential targets for the prognosis and treatment of PAAD.

Methods

RNA-sequence and clinical data of PAAD was downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) public databases. The PAAD samples were clustered by a non-negative matrix factorization (NMF) algorithm. The differentially expressed genes (DEGs) between different subtypes were used by “limma_3.42.2” package. The R software package clusterProfiler was used for functional enrichment analysis. Then, a multivariate Cox proportional and LASSO regression were used to develop a ferroptosis-related gene signature for pancreatic adenocarcinoma. A nomogram and corrected curves were constructed. Finally, the expression and function of these signature genes were explored by qRT-PCR, immunohistochemistry (IHC) and proliferation, migration and invasion assays.

Results

The 173 samples were divided into 3 categories (C1, C2, and C3) and a 3-gene signature model (ALOX5, ALOX12, and CISD1) was constructed. The prognostic model showed good independent prognostic ability in PAAD. In the GSE62452 external validation set, the molecular model also showed good risk prediction. KM-curve analysis showed that there were significant differences between the high and low-risk groups, samples with a high-risk score had a worse prognosis. The predictive efficiency of the 3-gene signature-based nomogram was significantly better than that of traditional clinical features. For comparison with other models, that our model, with a reasonable number of genes, yields a more effective result. The results obtained with qPCR and IHC assays showed that ALOX5 was highly expressed, whether ALOX12 and CISD1 were expressed at low levels in tissue samples. Finally, function assays results suggested that ALOX5 may be an oncogene and ALOX12 and CISD1 may be tumor suppressor genes.

Conclusions

We present a novel prognostic molecular model for PAAD based on ferroptosis-related genes, which serves as a potentially effective tool for prognostic differentiation in pancreatic cancer patients.
Study on the expression of TOP2A in hepatocellular carcinoma and its relationship with patient prognosis
Authors: Meng Jiali , Wei Yuanchao , Deng Qing , Li Ling , Li Xiaolong
Published: January 2022

Background

Hepatocellular carcinoma (HCC) is a primary liver cancer with a high mortality rate. However, the molecular mechanism of HCC formation remains to be explored and studied.

Objective

To investigate the expression of TOP2A in hepatocellular carcinoma (HCC) and its prognosis.

Methods

The data set of hepatocellular carcinoma was downloaded from GEO database for differential gene analysis, and hub gene was identified by Cytoscape. GEPIA was used to verify the expression of HUB gene and evaluate its prognostic value. Then TOP2A was selected as the research object of this paper by combining literature and clinical sample results. Firstly, TIMER database was used to study TOP2A, and the differential expression of TOP2A gene between normal tissues and cancer tissues was analyzed, as well as the correlation between TOP2A gene expression and immune infiltration of HCC cells. Then, the expression of top2a-related antibodies was analyzed using the Human Protein Atlas database, and the differential expression of TOP2A was verified by immunohistochemistry. Then, SRTING database and Cytoscape were used to establish PPI network for TOP2A and protein–protein interaction analysis was performed. The Oncomine database and cBioPortal were used to express and identify TOP2A mutation-related analyses. The expression differences of TOP2A gene were identified by LinkedOmics, and the GO and KEGG pathways were analyzed in combination with related genes. Finally, Kaplan–Meier survival analysis was performed to analyze the clinical and prognosis of HCC patients.

Results

TOP2A may be a new biomarker and therapeutic target for hepatocellular carcinoma.
The functions and prognostic value of Krüppel‐like factors in breast cancer
Authors: Zhu Ke-Yun , Tian Yao , Li Ying-Xi , Meng Qing-Xiang , Ge Jie , Cao Xu-Chen , Zhang Ti , Yu Yue
Published: January 2022

Background

Krüppel‐like factors (KLFs) are zinc finger proteins which participate in transcriptional gene regulation. Although increasing evidence indicate that KLFs are involved in carcinogenesis and progression, its clinical significance and biological function in breast cancer are still limited.

Methods

We investigated all the expression of KLFs (KLF1-18) at transcriptional levels by using Oncomine and Gene Expression Profiling Interactive Analysis (GEPIA). The mRNA and protein expression levels of KLFs were also determined by using RT-qPCR and immunohistochemistry, respectively. CBioPortal, GeneMANIA and STRING were used to comprehensive analysis of the molecular characteristics of KLFs. The clinical value of prognostic prediction based on the expression of KLFs was determined by using the KM plotter. The relevant molecular pathways of KLFs were further analyzed by using Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database. Finally, we investigated the effect of KLF2 and KLF15 on biological behavior of breast cancer cells in vitro.

Results

The expression of KLF2/4/6/8/9/11/15 was significantly down-regulated in breast cancer. The patients with high KLF2, KLF4 or KLF15 expression had a better outcome, while patients with high KLF8 or KLF11 had a poor prognosis. Furthermore, our results showed that KLF2 or KLF15 can be used as a prognostic factor independent on the other KLFs in patients with breast cancer. Overexpression of KLF2 or KLF15 inhibited cell proliferation and migration, and blocked cell cycle at G0/G1 phase, resulting in cell apoptosis.

Conclusions

KLF2 and KLF15 function as tumor suppressors in breast cancer and are potential biomarkers for prognostic prediction in patients with breast cancer.
Immune-related lncRNA classification of head and neck squamous cell carcinoma
Authors: Cao Ruoyan , Cui Lin , Zhang Jiayu , Ren Xianyue , Cheng Bin , Xia Juan
Published: January 2022

Background

Long noncoding RNAs (lncRNAs) play a critical role in innate and adaptive immune responses. Thus, we aimed to identify ideal subtypes for head and neck squamous cell carcinoma (HNSCC) based on immune-related lncRNAs.

Methods

TCGA HNSCC cohort was divided into two datasets (training and validation dataset), and 960 previously characterized immune-related lncRNAs were extracted for non-negative matrix factorization analysis. We characterized our HNSCC subtypes based on biological behaviors, immune landscape and response to immunotherapy in both training and validation cohort. A lncRNA-signature was generated to predict our HNSCC subtypes, and essential lncRNAs involved in tumor microenvironment (TME) were identified.

Results

We developed and validated two HNSCC subtypes (C1 and C2) based on the 70 lncRNAs in the training and validation cohort. C2 subtype displayed good prognosis, high immune cell infiltration, immune-related genes expression and sensitivity to PD-1 blockade. C1 subtype was associated with high activity of mTORC1 signaling and glycolysis as well as high fraction of inactive immune cells. Finally, we generated a 31-lncRNA signature that could predict our above subtypes with high accurate. Additionally, TRG-AS1 was identified as the essential lncRNA involving TME formation. Knockdown of TRG-AS1 inhibited the expression of HLA-A, HLA-B, HLA-C, CXCL9, CXCL10 and CXCL11. High expression of TRG-AS1 indicated a favorable prognosis in HNSCC and anti-PD-L1 cohort (IMvigor210).

Conclusions

Our study establishes a novel HNSCC classification on the basis of 31-lncRNA, helping to identify beneficiaries for anti-PD-1 treatment. In addition, a critical lncRNA TRG-AS1 is identified as a new potential prognosis biomarker as well as therapeutic target.
Horizontal inequity in the utilisation of Continuum of Maternal Health care Services (CMHS) in India: an investigation of ten years of National Rural Health Mission (NRHM)
Authors: Gandhi Sumirtha , Dash Umakant , Suresh Babu M.
Published: January 2022

Background

Continuum of Maternal Health Care Services (CMHS) has garnered attention in recent times and reducing socio-economic disparity and geographical variations in its utilisation becomes crucial from an egalitarian perspective. In this study, we estimate inequity in the utilisation of CMHS in India between 2005 and 06 and 2015-16.

Methods

We used two rounds of National Family Health Survey (NFHS) - 2005-06 and 2015-16 encompassing a sample size of 34,560 and 178,857 pregnant women respectively. The magnitude of horizontal inequities (HI) in the utilisation of CMHS was captured by adopting the Erreygers Corrected Concentration indices method. Need-based standardisation was conducted to disentangle the variations in the utilisation of CMHS across different wealth quintiles and state groups.  Further, a decomposition analysis was undertaken to enumerate the contribution of legitimate and illegitimate factors towards health inequity.

Results

The study indicates that the pro-rich inequity in the utilisation of CMHS has increased by around 2 percentage points since the implementation of National Rural Health Mission (NRHM), where illegitimate factors are dominant. Decomposition analysis reveals that the contribution of access related barriers plummeted in the considered period of time. The results also indicate that mother’s education and access to media continue to remain major contributors of pro-rich inequity in India. Considering, regional variations, it is found that the percentage of pro-rich inequity in high focus group states increased by around 3% between 2005 and 06 and 2015-16. The performance of southern states of India is commendable.

Conclusions

Our study concludes that there exists a pro-rich inequity in the utilisation of CMHS with marked variations across state boundaries. The pro-rich inequity in India has increased between 2005 and 06 and high focus group states suffered predominantly. Decentralisation of healthcare policies and  granting greater power to the states might lead to equitable distribution of CMHS.
Prenatal and early childhood exposure to tetrachloroethylene (PCE)-contaminated drinking water and sleep quality in adulthood: a retrospective cohort study
Authors: Doran Charlotte R. , Aschengrau Ann
Published: January 2022

Background

Communities in Cape Cod, Massachusetts were exposed to tetrachloroethylene (PCE) through contaminated drinking water from 1969 to 1983. PCE exposure during adulthood has well-established neurotoxic effects; however, long-term impacts stemming from early life exposure, especially adverse effects on sleep quality, are not well understood.

Methods

The present analysis was based on data from the Cape Cod Health Study, a retrospective cohort study of the long-term neurotoxic impacts of early-life exposure to PCE-contaminated drinking water. Exposure to PCE-contaminated water was estimated using a validated leaching and transport model. Measures of sleep quality were obtained from self-administered questionnaires. Generalized estimating equations were used to generate risk ratios and 95% confidence intervals to estimate the association between early-life PCE exposure and sleep quality among 604 participants.

Results

Compared to unexposed participants, any PCE exposure during early life was associated with 1.57 times the risk of reporting breathing pauses during sleep (95% CI 0.92–2.68). Low-level exposure to PCE was associated with 1.50 times the risk of reporting sleep apnea or other sleep disorders (95% CI 0.78–2.89), while high levels of exposure had comparable risk compared to no exposure (RR = 0.94, 95% CI 0.50–1.79). Weak or no associations were observed for other sleep quality outcomes. In stratified analyses participants with mental illness and/or substance use disorder had increased risk ratios for short sleep duration associated with PCE exposure.

Conclusion

These findings suggest that early-life exposure to PCE may be associated with a moderate increase in the risk of reporting breathing pauses during sleep in adulthood and that a history of mental illness and/or substance use disorder may exacerbate the risk of short sleep duration.
Neighborhood greenspace exposure as a protective factor in dementia risk among U.S. adults 75 years or older: a cohort study
Authors: Slawsky Erik D. , Hajat Anjum , Rhew Isaac C. , Russette Helen , Semmens Erin O. , Kaufman Joel D. , Leary Cindy S. , Fitzpatrick Annette L.
Published: January 2022

Background

Research suggests that greenspace may confer neurocognitive benefits. This study examines whether residential greenspace is associated with risk of dementia among older adults.

Methods

Greenspace exposure was computed for 3047 participants aged 75 years and older enrolled in the Gingko Evaluation of Memory Study (GEMS) across four U.S. sites that prospectively evaluated dementia and its subtypes, Alzheimer’s disease (AD), vascular dementia (VaD), and mixed pathologies, using neuropsychiatric evaluations between 2000 and 2008. After geocoding participant residences at baseline, three greenspace metrics—Normalized Difference Vegetative Index, percent park overlap within a 2-km radius, and linear distance to nearest park—were combined to create a composite residential greenspace measure categorized into tertiles. Cox proportional hazards models estimated the associations between baseline greenspace and risk of incident all-cause dementia, AD, and Mixed/VaD.

Results

Compared to low residential greenspace, high residential greenspace was associated with a reduced risk of dementia (HR = 0.76 95% CI: 0.59,0.98) in models adjusted for multiple covariates. After additional adjustment for behavioral characteristics, Apolipoprotein E ɛ4 status, and other covariates, the association was slightly attenuated (HR = 0.82; 95% CI:0.63,1.06). Those exposed to medium levels of greenspace also had 28% lower risk (HR = 0.72; CI: 0.55, 0.95) of dementia compared to those with low greenspace in adjusted models. Subtype associations between high residential greenspace and AD were not statistically significant. Greenspace was not found to be significantly associated with mixed/vascular pathologies.

Conclusions

This study showed evidence for an association between residential greenspace and all-cause dementia among older adults. Future research with larger sample size, precise characterization of different dementia subtypes, and assessment of residential greenspace earlier in life may help clarify the role between exposure to greenspace and dementia risk.
A nuclear function for an oncogenic microRNA as a modulator of snRNA and splicing
Authors: El Fatimy Rachid , Zhang Yanhong , Deforzh Evgeny , Ramadas Mahalakshmi , Saravanan Harini , Wei Zhiyun , Rabinovsky Rosalia , Teplyuk Nadiya M. , Uhlmann Erik J. , Krichevsky Anna M.
Published: January 2022

Background

miRNAs are regulatory transcripts established as repressors of mRNA stability and translation that have been functionally implicated in carcinogenesis. miR-10b is one of the key onco-miRs associated with multiple forms of cancer. Malignant gliomas exhibit particularly striking dependence on miR-10b. However, despite the therapeutic potential of miR-10b targeting, this miRNA’s poorly investigated and largely unconventional properties hamper the clinical translation.

Methods

We utilized Covalent Ligation of Endogenous Argonaute-bound RNAs and their high-throughput RNA sequencing to identify miR-10b interactome and a combination of biochemical and imaging approaches for target validation. They included Crosslinking and RNA immunoprecipitation with spliceosomal proteins, a combination of miRNA FISH with protein immunofluorescence in glioma cells and patient-derived tumors, native Northern blotting, and the transcriptome-wide analysis of alternative splicing.

Results

We demonstrate that miR-10b binds to U6 snRNA, a core component of the spliceosomal machinery. We provide evidence of the direct binding between miR-10b and U6, in situ imaging of miR-10b and U6 co-localization in glioma cells and tumors, and biochemical co-isolation of miR-10b with the components of the spliceosome. We further demonstrate that miR-10b modulates U6 N-6-adenosine methylation and pseudouridylation, U6 binding to splicing factors SART3 and PRPF8, and regulates U6 stability, conformation, and levels. These effects on U6 result in global splicing alterations, exemplified by the altered ratio of the isoforms of a small GTPase CDC42, reduced overall CDC42 levels, and downstream CDC42 -mediated effects on cell viability.

Conclusions

We identified U6 snRNA, the key RNA component of the spliceosome, as the top miR-10b target in glioblastoma. We, therefore, present an unexpected intersection of the miRNA and splicing machineries and a new nuclear function for a major cancer-associated miRNA.
Augmented EPR effect post IRFA to enhance the therapeutic efficacy of arsenic loaded ZIF-8 nanoparticles on residual HCC progression
Authors: Chen Xuehua , Huang Yongquan , Chen Hui , Chen Ziman , Chen Jiaxin , Wang Hao , Li Dan , Su Zhongzhen
Published: January 2022

Background

Insufficient radiofrequency ablation (IRFA) can promote the local recurrence and distal metastasis of residual hepatocellular carcinoma (HCC), which makes clinical treatment extremely challenging. In this study, the malignant transition of residual tumors after IRFA was explored. Then, arsenic-loaded zeolitic imidazolate framework-8 nanoparticles (As@ZIF-8 NPs) were constructed, and their therapeutic effect on residual tumors was studied.

Results

Our data showed that IRFA can dramatically promote the proliferation, induce the metastasis, activate the epithelial–mesenchymal transition (EMT) and accelerate the angiogenesis of residual tumors. Interestingly, we found, for the first time, that extensive angiogenesis after IRFA can augment the enhanced permeability and retention (EPR) effect and enhance the enrichment of ZIF-8 nanocarriers in residual tumors. Encouraged by this unique finding, we successfully prepared As@ZIF-8 NPs with good biocompatibility and confirmed that they were more effective than free arsenic trioxide (ATO) in sublethal heat-induced cell proliferation suppression, apoptosis induction, cell migration and invasion inhibition, and EMT reversal in vitro. Furthermore, compared with free ATO, As@ZIF-8 NPs exhibited remarkably increased therapeutic effects by repressing residual tumor growth and metastasis in vivo.

Conclusions

This work provides a new paradigm for the treatment of residual HCC after IRFA.

Graphical Abstract
Health-related quality of life among Ebola survivors in Sierra Leone: the role of socio-demographic, health-related and psycho-social factors
Authors: James Peter Bai , Wardle Jon , Gyasi Razak M. , Steel Amie , Adams Jon , Kabba John Alimamy , Bah Abdulai Jawo , Lahai Michael , Conteh Eugene B.
Published: January 2022

Background

Evidence of how social factors affect the health-related quality of life (HRQoL) of Ebola virus disease (EVD) survivors is limited. Our study explores the association between socio-demographic, health-related and psycho-social (stigma) factors and EVD survivors' health-related quality of life (HRQoL) in Sierra Leone.

Methods

We conducted a nationwide cross-sectional study among 358 EVD survivors between January and August 2018. We used a multistage sampling method to recruit EVD survivors, and the RAND 36-Item Health Survey item was used to assess the HRQoL. Data were analysed using descriptive statistics and multiple linear regression.

Results

When comparing by each dimension in relation to their respective summary scores, role limitation physical [0.00 (50.00)] and role limitation emotional [0.00 (33.33)] were the most affected physical health and mental health domains among EVD survivors respectively. EVD survivors who were older (β = − 3.90, 95% CI − 6.47 to − 1.32, p = 0.003), had no formal education (β = − 2.80, 95% CI − 5.16 to − 0.43, p = 0.021), experienced a unit increase in the number of post-Ebola symptoms (β = − 1.08, 95% CI − 1.74 to − 0.43, p < 0.001) and experienced a unit increase in enacted stigma (β = − 2.61, 95% CI − 4.02 to − 1.20, p < 0.001) were more likely to report a decreased level of physical health. EVD survivors who experienced a unit increase in the time spent in the Ebola treatment centre (β = − 0.60, 95% CI − 0.103 to − 0.18, p = 0.006) and those who experienced a unit increase in enacted Stigma were more likely to report decreased levels of mental health (β = − 1.50, 95% CI − 2.67 to − 0.33, p = 0.012).

Conclusion

Sociodemographic, health-related, and psycho-social factors were significantly associated with decrease levels of HRQoL. Our findings improve our understanding of the factors that might influence the HRQoL and suggest the need for EVD survivors to be provided with a comprehensive healthcare package that caters for their physical and mental health needs.
Blood cholesterol-to-lymphocyte ratio as a novel prognostic marker to predict postoperative overall survival in patients with colorectal cancer
Authors: Zhou Siyu , He Qian , Sheng Nengquan , Gong Jianfeng , Ren Jiazi , Wang Zhigang
Published: January 2022

Background

Lipid disequilibrium and systemic inflammation are reported to correlate with tumorigenesis and development of colorectal cancer (CRC). We construct the novel biomarker cholesterol-to-lymphocyte ratio (CLR) to reflect the synergistic effect of cholesterol metabolism and inflammation on CRC outcomes. This study aims to investigate the clinical significance of CLR and establish a prognostic model for CRC.

Methods

Our study retrospectively enrolled 223 CRC patients who underwent curative surgical resection. The Kaplan-Meier method was employed to estimate the overall survival (OS) rates, and the association between serological biomarkers and survival was assessed with a log-rank test. Cox proportional hazard regression was applied in the univariate and multivariate analyses to identify independent prognostic factors, which were then used to develop a predictive nomogram model for OS in CRC. The nomogram was evaluated by theC-index, receiver operator characteristic curve (ROC) analysis, and calibration plot. All cases were grouped into three stratifications according to the total risk points calculated from the nomogram, and the difference in OS between them was assessed with the Kaplan-Meier method.

Results

At the end of the study, death occurred in 47 (21%) cases. Patients with low CLR (< 3.23) had significantly prolonged survival (P< 0.001). Multivariate analyses revealed that N stage (P< 0.001), harvested lymph nodes (P= 0.021), and CLR (P= 0.005) were independent prognostic factors for OS and a prognostic nomogram was established based on these variables. The nomogram showed good calibration and predictive performance with a superiorC-index than TNM stage (0.755 (0.719–0.791) vs. 0.663 (0.629–0.697),P= 0.001). Patients of different risk stratifications based on the total score of nomogram showed distinct survival (P< 0.001).

Conclusions

The nomogram based on CLR and other clinical features can be used as a potentially convenient and reliable tool in predicting survival in patients with CRC.
Conceptualizing and implementing a health workforce registry in Nigeria
Authors: Okoroafor Sunny C. , Oaiya Agbonkhese I. , Oviaesu David , Ahmat Adam , Osubor Martin , Nyoni Jennifer
Published: January 2022

Background

Nigeria’s health sector aims to ensure that the right number of health workers that are qualified, skilled, and distributed equitably, are available for quality health service provision at all levels. Achieving this requires accurate and timely health workforce information. This informed the development of the Nigeria Health Workforce Registry (NHWR) based on the global, regional, and national strategies for strengthening the HRH towards achieving universal health coverage. This case study describes the process of conceptualizing and establishing the NHWR, and discusses the strategies for developing sustainable and scalable health workforce registries.

Case presentation

In designing the NHWR, a review of existing national HRH policies and guidelines, as well as reports of previous endeavors was done to learn what had been done previously and obtain the views of stakeholders on how to develop a scalable and sustainable registry. The findings indicated the need to review the architecture of the registry to align with other health information systems, develop a standardized data set and guidance documents for the registry including a standard operating procedure to ensure that a holistic process is adopted in data collection, management and use nationally. Learning from the findings, a conceptual framework was developed, a registry managed centrally by the Federal Ministry of Health was developed and decentralized, a standardized tool based on a national minimum data was developed and adopted nationally, a registry prototype was developed using iHRIS Manage and the registry governance functions were integrated into the health information system governance structures. To sustain the functionality of the NHWR, the handbook of the NHWR that comprised of an implementation guide, the standard operating procedure, and the basic user training manual was developed and the capacity of government staff was built on the operations of the registry.

Conclusion

In establishing a functional and sustainable registry, learning from experiences is essential in shaping acceptable, sustainable, and scalable approaches. Instituting governance structures that include and involve policymakers, health managers and users is of great importance in the design, planning, implementation, and decentralization stages. In addition, developing standardized tools based on the health system's needs and instituting supportable mechanisms for data flow and use for policy, planning, development, and management is essential.