bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between type of drinking water and upper gastrointestinal cancer incidence in the Linxian General Population
Authors: Yang Huan , Wang Jian-bing , Wang Xiao-kun , Fan Jin-hu , Qiao You-lin
Published: May 2023

Background

This study aimed to explore the association between drinking water source and risk of upper gastrointestinal (UGI) cancer, including esophageal cancer (EC) and gastric cancer (GC), in the Linxian General Population Nutrition Intervention Trial (NIT) cohort.

Methods

In this study, we used data from the Linxian NIT cohort, which included 29,584 healthy adults aged 40 to 69 years. Subjects were enrolled in April 1986 and followed up until March 2016. Tap water drinking status and demographic characteristics were collected at baseline. Subjects who drank tap water were treated as the exposed group. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated using the Cox proportional hazard model.

Results

A total of 5,463 cases of UGI cancer were identified during the 30-year follow-up period. After adjusting for multiple factors, the incidence rate of UGI cancer in participants who drank tap water was significantly lower compared with individuals in the control (HR = 0.91, 95% CI: 0.86–0.97). A similar association was observed between tap water drinking and EC incidence (HR = 0.89, 95% CI: 0.82–0.97). The association between drinking tap water and risk of UGI cancer and EC incidence did not vary across the subgroup by age and gender (All Pinteraction > 0.05). For EC incidence, an interaction effect was observed for riboflavin/niacin supplements and drinking water source (Pinteraction = 0.03). No association was observed between drinking water source and GC incidence.

Conclusions

In this prospective cohort study in Linxian, participants who drank tap water had a lower risk of EC incidence. As a source of drinking water, use of tap water may reduce the risk of EC by avoiding exposure to nitrate/nitrite. Measures should be taken to improve the quality of drinking water in high-incidence areas of EC.

Trial registration

The trial is registered with ClinicalTrials.gov (NCT00342654, 21/06/2006), and the trial name is Nutrition Intervention Trials in Linxian Follow-up Study.
Acupuncture for post-stroke depression: a systematic review and network meta-analysis
Authors: Lam Ching Wai , Li Hui Juan , Guo Jianwen , Yao Liang , Chau Janita , Lo Suzanne , Yuen Chun Sum , Ng Bacon Fung Leung , Chau-Leung Yu Edwin , Bian Zhaoxiang , Lau Alexander Y , Zhong Linda LD
Published: May 2023

Background

Patients with post-stroke depression (PSD) usually experience anxiety, hopelessness, and insomnia, which have a negative impact on their daily activities and post-stroke rehabilitation. Acupuncture (AC), as a minimally invasive technique, has become a popular choice for improving depression symptoms. However, it is still unclear which therapy is associated with the best outcomes for PSD. In this review, we aimed to explore the impact of AC in alleviating symptoms of PSD and to evaluate the difference in effectiveness between AC combined with pharmacotherapies and various non-pharmacotherapies.

Methods

Six databases and three clinical trials registration platforms were searched from inception to March 2023. Randomized clinical trial comparing needle-based AC with pharmacotherapy, and other non-pharmacotherapy or invalid group were included. Two independent reviewers identified eligible studies, and collected data using a pre-made form. A Bayesian network meta-analysis was conducted to assess and compare different techniques using RStudio 3.6.0 with the package ‘GEMTC’ V.0.8.1. The primary outcome was the efficacy for PSD assessed by scales measuring depressive symptoms. The secondary outcomes were effectiveness for neurological function and the quality of life. The ranking probabilities for all treatment interventions was performed using the Surface Under the Cumulative Ranking curve (SUCRA). The risk of bias was assessed by using the Revised Cochrane Risk of Bias tool 2.

Results

Sixty-two studies, involving 5308 participants published from 2003 to 2022, were included. The results showed that compared with western medicine (WM) (defined as pharmacotherapy for PSD), AC alone or with repetitive transcranial magnetic stimulation (RTMS), Traditional Chinese medicine (TCM) alone or with WM, were superior for alleviating depression symptoms. Compared to Usual Care, AC alone or plus other therapies could significantly decrease scores on the Hamilton Depression Rating scale. According to result of SUCRA, AC plus RTMS had the highest probability of improving depressive symptoms with a probability of 49.43%.

Conclusions

The results of this study indicate that AC alone or combined with other therapies appears to be effective in improving depression symptoms of stroke survivors. Moreover, in comparison to WM, AC alone or plus RTMS, TCM, TCM with WM, or WM, were more effective in improving depression symptoms of PSD. Also, AC with RTMS seems to be the most effective with the highest probability.

Registration

This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database in November 2020 and updated in July 2021. The registration number is CRD42020218752.
Machine learning-based prediction model for postoperative delirium in non-cardiac surgery
Authors: Lee Dong Yun , Oh Ah Ran , Park Jungchan , Lee Seung-Hwa , Choi Byungjin , Yang Kwangmo , Kim Ha Yeon , Park Rae Woong
Published: May 2023

Background

Postoperative delirium is a common complication that is distressing. This study aimed to demonstrate a prediction model for delirium.

Methods

Among 203,374undergoing non-cardiac surgery between January 2011 and June 2019 at Samsung Medical Center, 2,865 (1.4%) were diagnosed with postoperative delirium. After comparing performances of machine learning algorithms, we chose variables for a prediction model based on an extreme gradient boosting algorithm. Using the top five variables, we generated a prediction model for delirium and conducted an external validation. The Kaplan–Meier and Cox survival analyses were used to analyse the difference of delirium occurrence in patients classified as a prediction model.

Results

The top five variables selected for the postoperative delirium prediction model were age, operation duration, physical status classification, male sex, and surgical risk. An optimal probability threshold in this model was estimated to be 0.02. The area under the receiver operating characteristic (AUROC) curve was 0.870 with a 95% confidence interval of 0.855–0.885, and the sensitivity and specificity of the model were 0.76 and 0.84, respectively. In an external validation, the AUROC was 0.867 (0.845–0.877). In the survival analysis, delirium occurred more frequently in the group of patients predicted as delirium using an internal validation dataset (p < 0.001).

Conclusion

Based on machine learning techniques, we analyzed a prediction model of delirium in patients who underwent non-cardiac surgery. Screening for delirium based on the prediction model could improve postoperative care. The working model is provided online and is available for further verification among other populations.

Trial registration

KCT 0006363.
Cost-effectiveness analysis of sarcopenia management interventions in Iran
Authors: Darvishi Ali , Shafiee Gita , Balajam Narges Zargar , Hemami Mohsen Rezaei , Ostovar Navid , Heshmat Ramin
Published: May 2023

Objectives

Identification the optimal management intervention of sarcopenia is a concern of health systems. We aimed to analyze the cost-effectiveness of sarcopenia management strategies in Iran.

Methods

We constructed a lifetime Markov model based on natural history. The strategies comparedincluded exercise training, nutritional supplements, whole body vibration (WBV), and various exercise interventions and nutritional supplement combinations. A total of 7 strategies was evaluated in addition to the non-intervention strategy. Parameter values were extracted from primary data and the literature, and the costs and Quality-adjusted life years (QALYs) were calculated for each strategy. Deterministic and probabilistic sensitivity analysis, including the expected value of perfect information (EVPI), was also performed to determine the robustness of the model. Analyses were performed using the 2020 version of TreeAge Pro software.

Results

All seven strategies increased lifetime effectiveness (QALYs). The protein and Vitamin D3 (P + D) strategy had the highest effectiveness values among all strategies. After removing the dominated strategies, the estimated ICER for the P + D compared to Vitamin D3 alone (D) strategy was calculated as $131,229. Considering the cost-effectiveness threshold ($25,249), base-case results indicated that the D strategy was the most cost-effective strategy in this evaluation. Sensitivity analysis of model parameters also demonstrated the robustness of results. Also, EVPI was estimated at $273.

Conclusions

Study results, as the first economic evaluation of sarcopenia management interventions, showed that despite the higher effectiveness of D + P, the D strategy was the most cost-effective. Completing clinical evidence of various intervention options can lead to more accurate results in the future.
Dual A1 and A2A adenosine receptor antagonists, methoxy substituted 2-benzylidene-1-indanone, suppresses intestinal postprandial glucose and attenuates hyperglycaemia in fructose-streptozotocin diabetic rats
Authors: Sanni Olakunle , Terre’Blanche Gisella
Published: May 2023

Background/Aim

Recent research suggests that adenosine receptors (ARs) influence many of the metabolic abnormalities associated with diabetes. A non-xanthine benzylidene indanone derivative 2-(3,4-dihydroxybenzylidene)-4-methoxy-2,3-dihydro-1 H-inden-1-one (2-BI), has shown to exhibit higher affinity at A1/A2A ARs compared to caffeine. Due to its structural similarity to caffeine, and the established antidiabetic effects of caffeine, the current study was initiated to explore the possible antidiabetic effect of 2-BI.

Methods

The study was designed to assess the antidiabetic effects of several A1 and/or A2A AR antagonists, via intestinal glucose absorption and glucose-lowering effects in fructose-streptozotocin (STZ) induced diabetic rats. Six-week-old male Sprague-Dawley rats were induced with diabetes via fructose and streptozotocin. Rats were treated for 4 weeks with AR antagonists, metformin and pioglitazone, respectively. Non-fasting blood glucose (NFBG) was determined weekly and the oral glucose tolerance test (OGTT) was conducted at the end of the intervention period.

Results

Dual A1/A2A AR antagonists (caffeine and 2-BI) decreased glucose absorption in the intestinal membrane significantly (p < 0.01), while the selective A2A AR antagonist (Istradefylline), showed the highest significant (p < 0.001) reduction in intestinal glucose absorption. The selective A1 antagonist (DPCPX) had the least significant (p < 0.05) reduction in glucose absorption. Similarly, dual A1/A2A AR antagonists and selective A2A AR antagonists significantly reduced non-fast blood glucose and improved glucose tolerance in diabetic rats from the first week of the treatment. Conversely, the selective A1 AR antagonist did not reduce non-fast blood glucose significantly until the 4th week of treatment. 2-BI, caffeine and istradefylline compared well with standard antidiabetic treatments, metformin and pioglitazone, and in some cases performed even better.

Conclusion

2-BI exhibited good antidiabetic activity by reducing intestinal postprandial glucose absorption and improving glucose tolerance in a diabetic animal model. The dual antagonism of A1/A2A ARs presents a positive synergism that could provide a new possibility for the treatment of diabetes.
In vitro antioxidant and free-radical scavenging activities of polar leaf extracts of Vernonia amygdalina
Authors: Hussen Endris Muhie , Endalew Sisay Awoke
Published: May 2023

Background

Plants are able to deliver a huge number of differing bioactive compounds which may supplement the requirements of the human body by acting as natural antioxidants. Antioxidants are mindful for the defense component of the life form against the pathologies related to the assault of free radicals. The main purpose of this study was to investigate the qualitative phytochemical composition of Vernonia amygdalina leaf extract and its antioxidant activity.

Method

The powdered plant sample was successively extracted with aqueous, methanol and ethanol solvents using Soxhlet apparatus. The antioxidant activities of the crude leaf extract were determined using 1, 1- diphenyl-2-picryl hydrazyl (DPPH) radical, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical, phosphomolybdate (PM) and hydrogen peroxide (H2O2) scavenging assay. All the examinations were drained triplicates and average values of each test were taken.

Results

Phytochemical investigation of the plant revealed that the three solvent extracts contained numerous bioactive compounds namely alkaloids, tannins, saponins, phenols, terpenoids, steroids, glycosides and sugars. The result showed that, the leaf extracts of V. amygdalina obtained from methanol extract exhibit the maximum antioxidant activity compared ethanol and aqueous extracts. The IC50 values of DPPH assay for the H2O, MeOH and EtOH extracts were 111.4, 94.92 and 94.83 μg/ml; of ABTS assay were 334.3, 179.8 and 256.9 μg/ml; of H2O2 assay were 141.6, 156 and 180.6 μg/ml, respectively. The maximum radical scavenging activity was obtained in DPPH assay while the lowest scavenging activity was obtained in ABTS assay method. The data obtained in the in vitro models clearly suggest that methanol extract has higher antioxidant activity due to a higher presence of phenolic constituents in the extract.

Conclusion

This study revealed that V. amygdalina leaf has a noteworthy antioxidant and free radical scavenging activity mitigating the traditional use of the plant for different aliments.
Study on the absolute configuration and biological activity of rotenoids from the leaves and twigs of Millettia pyrrhocarpa Mattapha, Forest & Hawkins, sp. Nov
Authors: Sananboonudom Suda , Kaewnoi Atchara , Pompimon Wilart , Narakaew Samroeng , Jiajaroen Suwadee , Chainok Kittipong , nuntasaen Narong , Suksen Kanoknetr , Chairoungdua Arthit , Limthongkul Jitra , Naparswad Chanita , Pikulthong Suttiporn , Meepowpan Puttinan , Wingwon Boonthawan , Charoenphakinrattana Nichapa , Udomputtimekakul Phansuang
Published: May 2023

Background

M. pyrrhocarpa is a new plant in the Fabaceae: Faboideae family that is found in Thailand. A literature search revealed that the Milletia genus is rich in bioactive compounds possessing a wide range of biological activities. In this study, we aimed to isolate novel bioactive compounds and to study their bioactivities.

Methods

The hexane, ethyl acetate, and methanol extracts from the leaves and twigs of M. pyrrhocarpa were isolated and purified using chromatography techniques. These extracts and pure compounds were tested in vitro for their inhibitory activities against nine strains of bacteria, as well as their anti-HIV-1 virus activity and cytotoxicity against eight cancer cell lines.

Results

Three rotenoids, named 6aS, 12aS, 12S-elliptinol (1), 6aS, 12aS, 12S-munduserol (2), dehydromunduserone (3), and crude extracts were evaluated for antibacterial, anti-HIV, and cytotoxic activities. It was found that compounds 1–3 inhibited the growth of nine strains of bacteria, and the best MIC/MBC values were obtained at 3/ > 3 mg/mL. The hexane extract showed anti-HIV-1 RT with the highest %inhibition at 81.27 at 200 mg/mL, while 6aS, 12aS, 12S-elliptinol (1) reduced syncytium formation in 1A2 cells with a maximum EC50 value of 4.48 μM. Furthermore, 6aS, 12aS, 12S-elliptinol (1) showed cytotoxicity against A549 and Hep G2 cells with maximum ED50 values of 2.27 and 3.94 μg/mL.

Conclusion

This study led to the isolation of constituents with potential for medicinal application, providing compounds (1–3) as lead compounds against nine strains of bacteria. The hexane extract showed the highest %inhibition of HIV-1 virus, Compound 1 showed the best EC50 in reducing syncytium formation in 1A2 cells, and it also showed the best ED50 against human lung adenocarcinoma (A549) and human hepatocellular carcinoma (Hep G2). The isolated compounds from M. pyrrhocarpa offered significant potential for future medicinal application studies.
Iranian researchers’ perspective about concept and effect of open science on research publication
Authors: Zarghani Maryam , Nemati-Anaraki Leila , Sedghi Shahram , Chakoli Abdolreza Noroozi , Rowhani-Farid Anisa
Published: May 2023

Background

Sharing research outputs with open science methods for different stakeholders causes better access to different studies to solve problems in diverse fields, which leads to equal access conditions to research resources, as well as greater scientific productivity. Therefore, the aim of this study was to perceive the concept of openness in research among Iranian health researchers.

Methods

From the beginning of August to the middle of November 2021, twenty semi-structured interviews were held with Iranian health researchers from different fields using purposeful, snowball, and convenience sampling. The interviews continued until data saturation. Data analysis was performed with thematic analysis using MAXQDA 20. Finally, seven main issues related to open science were identified.

Results

Through analysis of the interviews, 235 primary codes and 173 main codes were extracted in 22 subclasses. After careful evaluation and integration of subclasses and classes, they were finally classified into nine categories and three main themes. Analysis showed that openness in research was related to three main themes: researchers’ understanding of open science, the impact of open science on publication and sharing of research, concerns and reluctance to open research.

Conclusion

The conditions of access to research output should be specified given the diversity of studies conducted in the field of health; issues like privacy as an important topic of access to data and information in the health system should also be specified. Our analysis indicated that the conditions of publication and sharing of research processes should be stated according to different scopes of health fields. The concept of open science was related to access to findings and other research items regardless of cost, political, social, or racial barriers, which could create collective wisdom in the development of knowledge. The process of publication and sharing of research related to open access applies to all types of outputs, conditions of access, increasing trust in research, creation of diverse publication paths, and broader participation of citizens in research. Open science practices should be promoted to increase the circulation and exploitation rates of knowledge while adjusting and respecting the limits of privacy, intellectual property and national security rights of countries.
aristaless1 has a dual role in appendage formation and wing color specification during butterfly development
Authors: Bayala Erick X. , VanKuren Nicholas , Massardo Darli , Kronforst Marcus R.
Published: May 2023

Background

Highly diverse butterfly wing patterns have emerged as a powerful system for understanding the genetic basis of phenotypic variation. While the genetic basis of this pattern variation is being clarified, the precise developmental pathways linking genotype to phenotype are not well understood. The gene aristaless, which plays a role in appendage patterning and extension, has been duplicated in Lepidoptera. One copy, aristaless1, has been shown to control a white/yellow color switch in the butterfly Heliconius cydno, suggesting a novel function associated with color patterning and pigmentation. Here we investigate the developmental basis of al1 in embryos, larvae, and pupae using new antibodies, CRISPR/Cas9, RNAi, qPCR assays of downstream targets, and pharmacological manipulation of an upstream activator.

Results

We find that Al1 is expressed at the distal tips of developing embryonic appendages consistent with its ancestral role. In developing wings, we observe Al1 accumulation within developing scale cells of white H. cydno during early pupation while yellow scale cells exhibit little Al1 at this time point. Reduced Al1 expression is also associated with yellow scale development in al1 knockouts and knockdowns. We propose that Al1 expression in future white scales might be related to an observed downregulation of the enzyme Cinnabar and other genes that synthesize and transport the yellow pigment, 3–hydroxykynurenine (3-OHK). Finally, we provide evidence that Al1 activation is under the control of Wnt signaling.

Conclusions

We propose a model in which high levels of Al1 during early pupation, which are mediated by Wnt, are important for melanic pigmentation and specifying white portions of the wing while reduced levels of Al1 during early pupation promote upregulation of proteins needed to move and synthesize 3-OHK, promoting yellow pigmentation. In addition, we discuss how the ancestral role of aristaless in appendage extension may be relevant in understanding the cellular mechanism behind color patterning in the context of the heterochrony hypothesis.
Detection of motor imagery based on short-term entropy of time–frequency representations
Authors: Batistić Luka , Lerga Jonatan , Stanković Isidora
Published: May 2023

Background

Motor imagery is a cognitive process of imagining a performance of a motor task without employing the actual movement of muscles. It is often used in rehabilitation and utilized in assistive technologies to control a brain–computer interface (BCI). This paper provides a comparison of different time–frequency representations (TFR) and their Rényi and Shannon entropies for sensorimotor rhythm (SMR) based motor imagery control signals in electroencephalographic (EEG) data. The motor imagery task was guided by visual guidance, visual and vibrotactile (somatosensory) guidance or visual cue only.

Results

When using TFR-based entropy features as an input for classification of different interaction intentions, higher accuracies were achieved (up to 99.87%) in comparison to regular time-series amplitude features (for which accuracy was up to 85.91%), which is an increase when compared to existing methods. In particular, the highest accuracy was achieved for the classification of the motor imagery versus the baseline (rest state) when using Shannon entropy with Reassigned Pseudo Wigner–Ville time–frequency representation.

Conclusions

Our findings suggest that the quantity of useful classifiable motor imagery information (entropy output) changes during the period of motor imagery in comparison to baseline period; as a result, there is an increase in the accuracy and F1 score of classification when using entropy features in comparison to the accuracy and the F1 of classification when using amplitude features, hence, it is manifested as an improvement of the ability to detect motor imagery.
Is there equity of patient health outcomes across models of general practice in Aotearoa New Zealand? A national cross-sectional study
Authors: Sheridan Nicolette , Love Tom , Kenealy Timothy ,   The Primary Care Models Study Group, Aguirre-Duarte Nelson , Arroll Bruce , Atmore Carol , Carryer Jenny , Crampton Peter , Dowell Anthony , Fishman Tana , Gauld Robin , Harwood Matire , Hoare Karen , Jackson Gary , Jansen Rawiri McKree , Kerse Ngaire , Lampshire Debra , McBain Lynn , MacRae Jayden , Mills Jane , Øvretveit John , Percival Teuila , Perera Roshan , Roland Martin , Ryan Debbie , Schmidt-Busby Jacqueline , Stokes Tim , Stubbe Maria , Hewitt Sarah , Watt Daniel , Peck Chris
Published: May 2023

Background

Primary care in Aotearoa New Zealand is largely delivered by general practices, heavily subsidised by government. Te Tiriti o Waitangi (1840) guarantees equal health outcomes for Māori and non-Māori, but differences are stark and longstanding. Seven models of primary care have evolved. We hypothesised that patient health outcomes would differ between models of care; and that Māori, Pacific peoples and those living in material deprivation would have poorer outcomes from primary care.

Methods

We conducted a cross-sectional study of patient-level data from national datasets and practices, at 30 September 2018, using multilevel mixed effects regression analyses (patients clustered within practices). Primary outcomes, considered to be measures of unmet need for primary care, were polypharmacy (≥ 65 years), HbA1c testing in adults with diabetes, childhood immunisations (6 months), ambulatory sensitive hospitalisations (0–14, 45–64 years) and emergency department attendances.

Explanatory variables adjusted for patient and practice characteristics. Equity, by model of care, ethnicity and deprivation, was assumed if they showed no significant association with patient outcomes.

Patient characteristics included: age, ethnicity, deprivation, multi-morbidity, first specialist assessments and practice continuity. Practice characteristics included: size, funding and doctor continuity. Clinical input (consultations and time with nurses and doctors) was considered a measure of practice response.

Results

The study included 924 general practices with 4,491,964 enrolled patients. Traditional practices enrolled 73% of the population, but, on average, the proportion of Māori, Pacific and people living with material deprivation was low in any one Traditional practice. Patients with high health needs disproportionately enrolled in Māori, Pacific and Trust/NGO practices.

There were multiple associations between models of care and patient health outcomes in fully adjusted regressions. No one model of care out-performed others across all outcomes. Patients with higher health need received more clinical input but this was insufficient to achieve equity in all outcomes. Being a Māori or Pacific patient, or living in material deprivation, across models of care, remained associated with poorer outcomes.

Conclusions

Model-level associations with poor patient outcomes suggest inequity in measures that might be used to target investment in primary care.
Systemic structural gender discrimination and inequality in the health workforce: theoretical lenses for gender analysis, multi-country evidence and implications for implementation and HRH policy
Authors: Newman Constance , Nayebare Alice , Gacko Ndeye Mingue Ndiate Ndiaye , Okello Patrick , Gueye Abdou , Bijou Sujata , Ba Selly , Gaye Sokhna , Coumba N’deye , Gueye Babacar , Dial Yankouba , N’doye Maimouna
Published: May 2023

This commentary brings together theory, evidence and lessons from 15 years of gender and HRH analyses conducted in health systems in six WHO regions to address selected data-related aspects of WHO’s 2016 Global HRH Strategy and 2022 Working for Health Action Plan. It considers useful theoretical lenses, multi-country evidence and implications for implementation and HRH policy. Systemic, structural gender discrimination and inequality encompass widespread but often masked or invisible patterns of gendered practices, interactions, relations and the social, economic or cultural background conditions that are entrenched in the processes and structures of health systems (such as health education and employment institutions) that can create or perpetuate disadvantage for some members of a marginalized group relative to other groups in society or organizations. Context-specific sex- and age-disaggregated and gender-descriptive data on HRH systems’ dysfunctions are needed to enable HRH policy planners and managers to anticipate bottlenecks to health workforce entry, flows and exit or retention. Multi-method approaches using ethnographic techniques reveal rich contextual detail. Accountability requires that gender and HRH analyses measure SDGs 3, 4, 5 and 8 targets and indicators. To achieve gender equality in paid work, women also need to achieve equality in unpaid work, underscoring the importance of SDG target 5.4. HRH policies based on principles of substantive equality and nondiscrimination are effective in countering gender discrimination and inequality. HRH leaders and managers can make the use of gender and HRH evidence a priority in developing transformational policy that changes the actual conditions and terms of health workers’ lives and work for the better. Knowledge translation and intersectoral coalition-building are also critical to effectiveness and accountability. These will contribute to social progress, equity and the realization of human rights, and expand the health care workforce. Global HRH strategy objectives and UHC and SDG goals will more likely be realized.
Disability weight measurement for the severity of different diseases in Wuhan, China
Authors: Liu Xiaoxue , Guo Yan , Wang Fang , Yu Yong , Yan Yaqiong , Wen Haoyu , Shi Fang , Wang Yafeng , Wang Xuyan , Shen Hui , Li Shiyang , Gong Yanyun , Ke Sisi , Zhang Wei , Jin Qiman , Zhang Gang , Wu Yu , Zhou Maigeng , Yu Chuanhua
Published: May 2023

Background

Measurement of the Chinese burden of disease with disability-adjusted life-years (DALYs) requires disability weight (DW) that quantify health losses for all non-fatal consequences of disease and injury. The Global Burden of Disease (GBD) 2013 DW study indicates that it is limited by lack of geographic variation in DW data and by the current measurement methodology. We aim to estimate DW for a set of health states from major diseases in the Wuhan population.

Methods

We conducted the DW measurement study for 206 health states through a household survey with computer-assisted face-to-face interviews and a web-based survey. Based on GBD 2013 DW study, paired comparison (PC) and Population health equivalence (PHE) method was used and different PC/PHE questions were randomly assigned to each respondent. In statistical analysis, the PC data was analyzed by probit regression. The probit regression results will be anchored by results from the PHE data analyzed by interval regression on the DW scale units between 0 (no loss of health) and 1 (loss equivalent to death).

Results

A total of 2610 and 3140 individuals were included in the household and web-based survey, respectively. The results from the total pooled data showed health state “mild anemia” (DW = 0.005, 95% UI 0.000–0.027) or “allergic rhinitis (hay fever)” (0.005, 95% UI 0.000–0.029) had the lowest DW and “heroin and other opioid dependence, severe” had the highest DW (0.699, 95% UI 0.579–0.827). A high correlation coefficient (Pearson’s r = 0.876; P < 0.001) for DWs of same health states was observed between Wuhan’s survey and GBD 2013 DW survey. Health states referred to mental symptom, fatigue, and the residual category of other physical symptoms were statistically significantly associated with a lower Wuhan’s DWs than the GBD’s DWs. Health states with disfigurement and substance use symptom had a higher DW in Wuhan population than the GBD 2013 study.

Conclusions

This set of DWs could be used to calculate local diseases burden for health policy-decision in Wuhan population. The DW differences between the GBD’s survey and Wuhan’s survey suggest that there might be some contextual or culture factors influencing assessment on the severity of diseases.
mTOR-dependent TFEB activation and TFEB overexpression enhance autophagy-lysosome pathway and ameliorate Alzheimer's disease-like pathology in diabetic encephalopathy
Authors: Cheng Lizhen , Chen Yixin , Guo Donghao , Zhong Yuan , Li Wei , Lin Yijia , Miao Ya
Published: May 2023

Background

Diabetic encephalopathy (DE) is a complication of type 2 diabetes mellitus (T2DM) that features Alzheimer's disease (AD)-like pathology, which can be degraded by the autophagy-lysosome pathway (ALP). Since transcription factor EB (TFEB) is a master regulator of ALP, TFEB-mediated ALP activation might have a therapeutic effect on DE, but this has yet to be investigated.

Methods

We established T2DM mouse models and cultured HT22 cells under high-glucose (HG) conditions to confirm the role of ALP in DE. To further investigate this, both mice and HT22 cells were treated with 3-methyladenine (3-MA). We also analyzed the content of TFEB in the nucleus and cytoplasm to evaluate its role in ALP. To confirm the effect of TFEB activation at the post-translational level in DE, we used rapamycin to inhibit the mechanistic target of rapamycin (mTOR). We transduced both mice and cells with TFEB vector to evaluate the therapeutic effect of TFEB overexpression on DE. Conversely, we conducted TFEB knockdown to verify its role in DE in another direction.

Results

We found that T2DM mice experienced compromised cognitive function, while HG-cultured HT22 cells exhibited increased cell apoptosis. Additionally, both T2DM mice and HG-cultured HT22 cells showed impaired ALP and heavier AD-like pathology. This pathology worsened after treatment with 3-MA. We also observed decreased TFEB nuclear translocation in both T2DM mice and HG-cultured HT22 cells. However, inhibiting mTOR with rapamycin or overexpressing TFEB increased TFEB nuclear translocation, enhancing the clearance of ALP-targeted AD-like pathology. This contributed to protection against neuronal apoptosis and alleviation of cognitive impairment. Conversely, TFEB knockdown lessened ALP-targeted AD-like pathology clearance and had a negative impact on DE.

Conclusion

Our findings suggest that impaired ALP is responsible for the aggravation of AD-like pathology in T2DM. We propose that mTOR-dependent TFEB activation and TFEB overexpression are promising therapeutic strategies for DE, as they enhance the clearance of ALP-targeted AD-like pathology and alleviate neuronal apoptosis. Our study provides insight into the underlying mechanisms of DE and offers potential avenues for the development of new treatments for this debilitating complication of T2DM.

Graphic Abstract
Change in cytokine profiles released by mast cells mediated by lung cancer-derived exosome activation may contribute to cancer-associated coagulation disorders
Authors: Ben Suqin , Huang Xiulin , Shi Yongxin , Xu Ziheng , Xiao Hui
Published: May 2023

Background

Coagulation disorders are a significant cause of lung cancer mortality. Although mast cells are known to play a role in coagulation abnormalities, their specific role in this process has not yet been elucidated.

Method

We detected mast cells in the tumor microenvironment using single-cell sequencing data and examined their correlation with thrombosis-related genes, neutrophil-related genes, neutrophil extracellular trap-related signature genes, and immune infiltration levels in lung cancer patients through bioinformatics analysis. Bone marrow mast cell uptake of exosomes isolated from the lung adenocarcinoma cell line A549, which were labeled using PKH67, was observed using confocal microscopy. Mast cell degranulation was detected by measuring the β-hexosaminidase release rate. Additionally, cytokine array analysis was performed to identify altered mediators released by bone marrow mast cells after uptake of the exosomes.

Results

In our study, we found a close correlation between the proportion of mast cells in lung cancer patients and the expression levels of thrombosis-related genes and neutrophil extracellular trap signature genes, both of which play a key role in thrombophilic disorder. Moreover, we discovered that lung cancer cell-derived exosomes can be taken up by mast cells, which in turn become activated to release procoagulant mediators.

Conclusion

Our study shows that exosomes derived from lung cancer cells can activate mast cells to release procoagulants that may contribute to abnormal blood clotting in lung cancer patients.
Phase separation propensity of the intrinsically disordered AB region of human RXRβ
Authors: Sołtys Katarzyna , Ożyhar Andrzej
Published: May 2023

RXRβ is one of three subtypes of human retinoid X receptor (RXR), a transcription factor that belongs to the nuclear receptor superfamily. Its expression can be detected in almost all tissues. In contrast to other subtypes – RXRα and RXRγ – RXRβ has the longest and unique N-terminal sequence called the AB region, which harbors a ligand-independent activation function. In contrast to the functional properties of this sequence, the molecular properties of the AB region of human RXRβ (AB_hRXRB) have not yet been characterized. Here, we present a systematic biochemical and biophysical analysis of recombinant AB_hRXRB, along with in silico examinations, which demonstrate that AB_hRXRB exhibits properties of a coil-like intrinsically disordered region. AB_hRXRB possesses a flexible structure that is able to adopt a more ordered conformation under the influence of different environmental factors. Interestingly, AB_hRXRB promotes the formation of liquid–liquid phase separation (LLPS), a phenomenon previously observed for the AB region of another human subtype of RXR – RXRγ (AB_hRXRG). Although both AB regions seem to be similar in terms of their ability to induce phase separation, they clearly differ in the sensitivity to factors driving and regulating LLPS. This distinct LLPS response to environmental factors driven by the unique amino acid compositions of AB_hRXRB and AB_hRXRG can be significant for the specific modulation of the transcriptional activation of target genes by different subtypes of RXR.
What is new in cancer-associated fibroblast biomarkers?
Authors: Zhao Zehua , Li Tianming , Yuan Yuan , Zhu Yanmei
Published: May 2023

The tumor microenvironment is one of the important drivers of tumor development. Cancer-associated fibroblasts (CAFs) are a major component of the tumor stroma and actively participate in tumor development, invasion, metastasis, drug resistance, and other biological behaviors. CAFs are a highly heterogeneous group of cells, a reflection of the diversity of their origin, biomarkers, and functions. The diversity of CAF origin determines the complexity of CAF biomarkers, and CAF subpopulations expressing different biomarkers may play contrasting roles in tumor progression. In this review, we provide an overview of these emerging CAF biomarkers and the biological functions that they suggest, which may give a better understanding of the relationship between CAFs and tumor cells and be of great significance for breakthroughs in precision targeted therapy for tumors.
Assessing temporal differences in the predictive power of baseline TyG-related parameters for future diabetes: an analysis using time-dependent receiver operating characteristics
Authors: Kuang Maobin , Yang Ruijuan , Huang Xin , Wang Chao , Sheng Guotai , Xie Guobo , Zou Yang
Published: May 2023

Background

It is known that measuring the triglyceride glucose (TyG) index and TyG-related parameters [triglyceride glucose-body mass index (TyG-BMI), triglyceride glucose-waist circumference (TyG-WC), and triglyceride glucose-waist to height ratio (TyG-WHtR)] can predict diabetes; this study aimed to compare the predictive value of the baseline TyG index and TyG-related parameters for the onset of diabetes at different future periods.

Methods

We conducted a longitudinal cohort study involving 15,464 Japanese people who had undergone health physical examinations. The subject’s TyG index and TyG-related parameters were measured at the first physical examination, and diabetes was defined according to the American Diabetes Association criteria. Multivariate Cox regression models and time-dependent receiver operating characteristic (ROC) curves were constructed to examine and compare the risk assessment/predictive value of the TyG index and TyG-related parameters for the onset of diabetes in different future periods.

Results

The mean follow-up period of the current study cohort was 6.13 years, with a maximum of 13 years, and the incidence density of diabetes was 39.88/10,000 person-years. In multivariate Cox regression models with standardized hazard ratios (HRs), we found that both the TyG index and TyG-related parameters were significantly and positively associated with diabetes risk and that the TyG-related parameters were stronger in assessing diabetes risk than the TyG index, with TyG-WC being the best parameter (HR per SD increase: 1.70, 95% CI 1.46, 1.97). In addition, TyG-WC also showed the highest predictive accuracy in time-dependent ROC analysis for diabetes occurring in the short-term (2–6 years), while TyG-WHtR had the highest predictive accuracy and the most stable predictive threshold for predicting the onset of diabetes in the medium- to long-term (6–12 years).

Conclusions

These results suggest that the TyG index combined with BMI, WC, and WHtR can further improve its ability to assess/predict the risk of diabetes in different future periods, where TyG-WC was not only the best parameter for assessing diabetes risk but also the best risk marker for predicting future diabetes in the short-term, while TyG-WHtR may be more suitable for predicting future diabetes in the medium- to long-term.
Pathogenic mechanisms and regulatory factors involved in alcoholic liver disease
Authors: Yan Chuyun , Hu Wanting , Tu Jinqi , Li Jinyao , Liang Qionglin , Han Shuxin
Published: May 2023

Alcoholism is a widespread and damaging behaviour of people throughout the world. Long-term alcohol consumption has resulted in alcoholic liver disease (ALD) being the leading cause of chronic liver disease. Many metabolic enzymes, including alcohol dehydrogenases such as ADH, CYP2E1, and CATacetaldehyde dehydrogenases ALDHsand nonoxidative metabolizing enzymes such as SULT, UGT, and FAEES, are involved in the metabolism of ethanol, the main component in alcoholic beverages. Ethanol consumption changes the functional or expression profiles of various regulatory factors, such as kinases, transcription factors, and microRNAs. Therefore, the underlying mechanisms of ALD are complex, involving inflammation, mitochondrial damage, endoplasmic reticulum stress, nitrification, and oxidative stress. Moreover, recent evidence has demonstrated that the gut-liver axis plays a critical role in ALD pathogenesis. For example, ethanol damages the intestinal barrier, resulting in the release of endotoxins and alterations in intestinal flora content and bile acid metabolism. However, ALD therapies show low effectiveness. Therefore, this review summarizes ethanol metabolism pathways and highly influential pathogenic mechanisms and regulatory factors involved in ALD pathology with the aim of new therapeutic insights.
Admission control policy and key agreement based on anonymous identity in cloud computing
Authors: Paulraj D. , Neelakandan S. , Prakash M. , Baburaj E.
Published: May 2023

Cloud computing has completely revolutionized the concept of computing by providing users with always-accessible resources. In terms of computational, storage, bandwidth, and transmission costs, cloud technology offers its users an entirely new set of advantages and cost savings. Cross-cloud data migration, required whenever a user switches providers, is one of the most common issues the users encounter. Due to smartphones’ limited local storage and computational power, it is often difficult for users to back up all data from the original cloud servers to their mobile phones to upload and download the data to the new cloud provider. Additionally, the user must remember numerous tokens and passwords for different applications. In many instances, the anonymity of users who access any or all services provided by this architecture must be ensured. Outsourcing IT resources carries risks, particularly regarding security and privacy, because cloud service providers manage and control all data and resources stored in the cloud. However, cloud users would prefer that cloud service providers not know the services they employ or the frequency of their use. Consequently, developing privacy protections takes a lot of work. We devised a system of binding agreements and anonymous identities to address this problem. Based on a binding contract and admission control policy (ACP), the proposed model facilitates cross-cloud data migration by fostering cloud provider trust. Finally, Multi-Agent Reinforcement Learning Algorithm (MARL) is applied to identify and classify anonymity in the cloud by conducting various pre-processing techniques, feature selection, and dimensionality reduction.
Excellent clinical outcomes of renal transplant from pediatric deceased donors with acute kidney injury
Authors: Liu Qiuhao , Zhang Hedong , Zhong Mingda , Tan Liang , Hu Shanbiao , Peng Longkai , Xie Xubiao , Lan Gongbin
Published: May 2023

Background

The use of kidneys from deceased donors with acute kidney injury (AKI) to expand the donor pool is an ongoing trend. Prior research on the utilization of AKI donor kidneys, especially from pediatric AKI donors, was limited and has been subject to small sample sizes. In this study, we aimed to evaluate the safety and effectiveness of early post-transplantation outcomes in pediatric deceased donors with AKI.

Methods

This retrospective study compared the clinical results (including delayed graft function [DGF], acute rejection, patient and death-censored graft survival rates and renal function post-transplant) of kidney transplantation from deceased donors who were categorized as pediatric donors and adult donors with or without AKI, as defined by the Kidney Disease: Improving Global Outcomes (KIDGO) criteria, at our center between January 2018 and December 2020.

Results

Of the 740 patients, 154 received kidneys from pediatric donors (with AKI group [n = 41]; without AKI group [n = 113]), and 586 received kidneys from adult donors (with AKI group [n = 218]; without AKI group [n = 368]). The baseline characteristics were similar in both cohorts. No significant difference was observed in 1-year patient survival, death-censored graft survival, or acute rejection between the AKI and non-AKI groups in both the pediatric and adult cohorts. However, compared with those transplanted with adult AKI kidneys, those transplanted with pediatric AKI kidneys showed a superior recovery of allograft function. In pediatric cohorts, no significant difference was found in serum creatinine/estimated glomerular filtration rate (SCr/eGFR) between the AKI and non-AKI groups, even in the first week post-transplant. In contrast, the post-transplant SCr/eGFR level of the AKI group recipients in adult cohorts did not recover to a level statistically similar to that of non-AKI recipients, even at 6-months post-transplant. Nonetheless, AKI kidney recipients were at an increased risk of DGF in both pediatric (34.1% vs. 16.8%) and adult (38.5% vs. 17.4%) cohorts.

Conclusions

Kidney transplantation from deceased donors with AKI has short-term clinical outcomes comparable to those of non-AKI kidney transplantation. Pediatric AKI kidneys have a superior recovery of allograft function. The transplant community should utilize this donor pool to minimize waiting-list-related mortalities.