bluuebunny/crossref_metadata_2025 huggingface dataset:
Temperature variability and common diseases of the elderly in China: a national cross-sectional study
Authors: Wen Bo , Su Bin Bin , Xue Jiahui , Xie Junqing , Wu Yao , Chen Li , Dong Yanhui , Wu Xiaolan , Wang Mengfan , Song Yi , Ma Jun , Zheng Xiaoying
Published: January 2023

Background

In the context of climate change, it has been well observed that short-term temperature variability (TV) could increase the overall and cause-specific mortality and morbidity. However, the association between long-term TV and a broader spectrum of diseases is not yet well understood, especially in the elderly.

Methods

Our study used data from the fourth Urban and Rural Elderly Population (UREP) study. Long-term TV was calculated from the standard deviation (SD) of daily minimum and maximum temperatures within the study periods (2010–2014, 2011–2014, 2012–2014, 2013–2014, and 2014). Ten self-reported diseases and conditions were collected by questionnaire, including cataract, hypertension, diabetes, cardio-cerebrovascular diseases, stomach diseases, arthritis, chronic lung disease, asthma, cancer, and reproductive diseases. The province-stratified logistic regression model was used to quantify the association between long-term TV and the prevalence of each disease.

Results

A total of 184,047 participants were included in our study. In general, there were significant associations between TV and the prevalence of most diseases at the national level. Cardio-cerebrovascular disease (OR: 1.16, 95% CI: 1.13, 1.20) generated the highest estimates, followed by stomach diseases (OR: 1.15, 95% CI: 1.10, 1.19), asthma (OR: 1.14, 95% CI: 1.06, 1.22), chronic lung diseases (OR: 1.08, 95% CI: 1.03, 1.13), arthritis (OR: 1.08, 95% CI: 1.05, 1.11), and cataract (OR: 1.06, 95% CI: 1.02, 1.10). Moreover, the associations varied by geographical regions and across subgroups stratified by sex, household income, physical activity, and education.

Conclusions

Our study showed that long-term exposure to TV was associated with the prevalence of main diseases in the elderly. More attention should be paid to the elderly and targeted strategies should be implemented, such as an early warning system.
Safety and feasibility of intranasal heroin-assisted treatment: 4-week preliminary findings from a Swiss multicentre observational study
Authors: Vogel Marc , Meyer Maximilian , Westenberg Jean N. , Kormann Adrian , Simon Olivier , Salim Hassan Fadlelseed Roba , Kurmann Markus , Bröer Rebecca , Devaud Nathalie , Sanwald Ulrike , Baumgartner Sophie , Binder Hannes , Strasser Johannes , Krausz R. Michael , Beck Thilo , Dürsteler Kenneth M. , Falcato Luis
Published: January 2023

Background

Heroin-assisted treatment (HAT) is effective for individuals with severe opioid use disorder (OUD) who do not respond sufficiently to other opioid agonist treatments. It is mostly offered with injectable diacetylmorphine (DAM) or DAM tablets creating a barrier for individuals who need the rapid onset of action but are either unable or unwilling to inject, or primarily snort opioids. To explore another route of administration, we evaluated the safety and feasibility of intranasal (IN) DAM.

Methods

This is a multicentre observational cohort study among patients in Swiss HAT. All patients planning to receive IN DAM within the treatment centres were eligible to participate. Participants were either completely switched to IN DAM or received IN DAM in addition to other DAM formulations or opioid agonists. Patients were followed up for four weeks. Sociodemographic characteristics, current HAT regimen, reasons for starting IN DAM, IN DAM doses, number of injection events in the sample, IN DAM continuation rate, and appearance of adverse events and nose-related problems were evaluated.

Results

Participants (n = 52) reported vein damage, preference for nasal route of administration, and desire of a stronger effect or for a less harmful route of administration as primary reasons for switching to IN DAM. After four weeks, 90.4% of participants (n = 47) still received IN DAM. Weekly average realised injection events decreased by 44.4% from the month before IN DAM initiation to the month following. No severe adverse events were reported.

Conclusions

After four weeks, IN DAM was a feasible and safe alternative to other routes of administration for patients with severe OUD in HAT. It addressed the needs of individuals with OUD and reduced injection behaviour. More long-term research efforts are needed to systematically assess efficacy of and patient satisfaction with IN DAM.
Aa-Z2 triggers ROS-induced apoptosis of osteosarcoma by targeting PDK-1
Authors: Liu Yixin , She Wenyan , Li Yi , Wang Miao , Liu Yin , Ning Biao , Xu Tianzi , Huang Tianhe , Wei Yongchang
Published: January 2023

Background

Osteosarcoma (OS) is the most frequent cancer derived from bone, and the prognosis of OS is poor. Metabolic alterations have been previously reported to contribute to the development of OS, and arsenic compounds have been suggested to exhibit strong anti-OS effects. However, few studies have described the therapeutic efficiency of arsenic compounds by targeting metabolism in OS.

Methods

Here, we presented a novel organo-arsenic compound, Aa-Z2, and its antitumour efficacy against OS both in vitro and in vivo.

Results

Aa-Z2 induced OS cell apoptosis, G2/M phase arrest, and autophagy through the accumulation of reactive oxygen species (ROS). Elevated ROS functioned by promoting the mitochondrial-dependent caspase cascade and attenuating the PI3K/Akt/mTOR signalling pathway. N-acetylcysteine (NAC), a kind of ROS scavenger, could reverse the effects of Aa-Z2 treatment on 143B and HOS cells. Specifically, by targeting pyruvate dehydrogenase kinase 1 (PDK-1), Aa-Z2 induced changes in mitochondrial membrane potential and alterations in glucose metabolism to accumulate ROS. Overexpression of PDK-1 could partially desensitize OS cells to Aa-Z2 treatment. Importantly, Aa-Z2 suppressed tumour growth in our xenograft osteosarcoma model.

Conclusion

The study provides new insights into the mechanism of Aa-Z2-related metabolic alterations in OS inhibition, as well as pharmacologic evidence supporting the development of metabolism-targeting therapeutics.
A proposal for systematic monitoring of the commercial determinants of health: a pilot study assessing the feasibility of monitoring lobbying and political donations in Australia
Authors: Lacy-Nichols Jennifer , Cullerton Katherine
Published: January 2023

Background

The commercial determinants of health include a range of practices to promote business interests, often at the expense of public health. Corporate political practices, such as lobbying and campaign donations, are used to influence policy makers and foster a political and regulatory environment conducive to business interests. Despite recognition of their public health importance, thus far there are relatively few efforts to systematically monitor commercial political practices.

Methods

A pilot study was conducted to explore the feasibility of systematically monitoring two political practices – lobbying and political contributions – for ‘harmful industries’ (alcohol, gambling, ultra-processed food and tobacco industries) in Australia. Potential data sources were reviewed to compare data availability and detail. Two publicly available datasets were selected for the pilot: ministerial diaries for New South Wales and annual donor filings from the Australian Electoral Commission. Google Data Studio was used to analyse and visualise findings. 

Results

The pilot study resulted in the creation of several interactive charts and dashboards that supported analysis and interrogation of the data. These charts helped to easily convey the volume of lobbying and political donations, as well as changes over time. For example, we found that between July 2014 and December 2020, NSW ministers had 20,607 meetings, of which 634 meetings were with harmful industries. And between 1998 and 2020, a total of $576,519,472 disclosed donations were made to political parties and other entities, of which $35,823,937 were from harmful industries.

Conclusions

Opportunities to develop a program to monitor commercial political practices face several challenges including access barriers arising from poor availability and detail of data, technical barriers arising from the format of data disclosures and coding challenges arising from the diverse nature of the commercial sector. Despite these challenges, our pilot study demonstrates the potential to implement a monitoring program and to expand its scope to other commercial determinants of health.
Safety and efficacy of two-port thoracoscopic aortic valve replacement
Authors: Tan Tong , Wei Peijian , Liu Yanjun , Huang Huanlei , Zhuang Jian , Chen Jimei , Liu Jian , Guo Huiming
Published: January 2023

Background

Pure aortic valve disease is common and has been treated with sternotomy aortic valve replacement for decades. Minimally invasive cardiac surgery has been widely used in atrioventricular valve lesions, but totally thoracoscopic aortic valve replacement has rarely been reported.

Method

The profiles of 9 patients who were diagnosed with severe aortic valve diseases and treated with two-port thoracoscopic aortic valve replacement between February 2021 and February 2022 were retrospectively reviewed. The clinical data, including baseline characteristics, operative data, postoperative complications, and short-term outcomes, were reported.

Results

All nine patients successfully underwent two-port thoracoscopic aortic valve replacement, with a cardiopulmonary bypass time of 137.56 ± 27.99 min and an aortic cross-clamp time of 95.33 ± 17.96 min. Seven (77.78%) patients underwent mechanical valve replacement, and two (22.22%) patients underwent bioprosthetic valve replacement. Two (22.22%) patients underwent a concomitant aortic root enlargement procedure. There were no intraoperative or postoperative deaths. The incidence of procedural complications was 0%, while the results of ventilation time, intensive care unit stay length, blood transfusion, chest tube drainage, and kidney function were satisfactory.

Conclusion

Two-port thoracoscopic aortic valve replacement is a safe and effective surgical treatment option for carefully selected patients with pure aortic valve diseases.
Genome-wide association study of brain biochemical phenotypes reveals distinct genetic architecture of Alzheimer’s disease related proteins
Authors: Oatman Stephanie R. , Reddy Joseph S. , Quicksall Zachary , Carrasquillo Minerva M. , Wang Xue , Liu Chia-Chen , Yamazaki Yu , Nguyen Thuy T. , Malphrus Kimberly , Heckman Michael , Biswas Kristi , Nho Kwangsik , Baker Matthew , Martens Yuka A. , Zhao Na , Kim Jun Pyo , Risacher Shannon L. , Rademakers Rosa , Saykin Andrew J. , DeTure Michael , Murray Melissa E. , Kanekiyo Takahisa ,   for the Alzheimer’s Disease Neuroimaging Initiative, Dickson Dennis W. , Bu Guojun , Allen Mariet , Ertekin-Taner Nilüfer
Published: January 2023

Background

Alzheimer’s disease (AD) is neuropathologically characterized by amyloid-beta (Aβ) plaques and neurofibrillary tangles. The main protein components of these hallmarks include Aβ40, Aβ42, tau, phosphor-tau, and APOE. We hypothesize that genetic variants influence the levels and solubility of these AD-related proteins in the brain; identifying these may provide key insights into disease pathogenesis.

Methods

Genome-wide genotypes were collected from 441 AD cases, imputed to the haplotype reference consortium (HRC) panel, and filtered for quality and frequency. Temporal cortex levels of five AD-related proteins from three fractions, buffer-soluble (TBS), detergent-soluble (Triton-X = TX), and insoluble (Formic acid = FA), were available for these same individuals. Variants were tested for association with each quantitative biochemical measure using linear regression, and GSA-SNP2 was used to identify enriched Gene Ontology (GO) terms. Implicated variants and genes were further assessed for association with other relevant variables.

Results

We identified genome-wide significant associations at seven novel loci and the APOE locus. Genes and variants at these loci also associate with multiple AD-related measures, regulate gene expression, have cell-type specific enrichment, and roles in brain health and other neuropsychiatric diseases. Pathway analysis identified significant enrichment of shared and distinct biological pathways.

Conclusions

Although all biochemical measures tested reflect proteins core to AD pathology, our results strongly suggest that each have unique genetic architecture and biological pathways that influence their specific biochemical states in the brain. Our novel approach of deep brain biochemical endophenotype GWAS has implications for pathophysiology of proteostasis in AD that can guide therapeutic discovery efforts focused on these proteins.
Evaluation of thiol disulfide balance in adolescents with vitamin B12 deficiency
Authors: Demirtas Mehmet Semih , Erdal Huseyin
Published: January 2023

Background

Vitamin B12 is an important vitamin for metabolism and affects many mechanisms in the body including neuronal migration, DNA synthesis, neurotransmitter synthesis, brain and cognitive development. Increased oxidative stress in the body leads to the damage of the child development, but also plays a crucial role in the pathogenesis of many diseases encountered in the childhood period. Our aim is to investigate whether or not B12 deficiency is associated with dynamic thiol/disulfide homeostasis in adolescent patients.

Methods

This is a case-controlled observational study consisting of 45 adolescent patients with vitamin b12 deficiency and a control group consisting of 45 healthy adolescent. Patients between 11 and 18 ages who applied to the outpatient clinic for the first time with one of the complaints of headache were selected due to their decreased school performance, dizziness, and fatigue. Hemogram, vitamin B12, homocysteine levels and oxidative stress parameters such as native and total thiol disulfide levels and ratios of disulfide/native thiol, disulfide/total thiol, and native thiol/total thiol were measured from the patients.

Results

Vitamin B12 level was found to be significantly lower in vitamin B12 deficiency group (p < 0.001). The serum disulfide level was found to be 27.5 ± 8.38 in the case group and 20.5 ± 8.36 in the control group (p < 0.001). In the multiple linear regression analysis, it was determined that the independent variables of native thiol, homocysteine and disulfide levels effected of vitamin B12 levels (p < 0.001, p < 0.001, p < 0.005 respectively; R2 = 0.62).

Conclusion

The results obtained in terms of the effect of vitamin B12 deficiency on oxidative stress in adolescents are remarkable. The increase in oxidative stress parameters in the patient group may also suggest that oxidative stress plays a vital role in vitamin B12 deficiency in adolescence.
Implementation of an evidence-based management algorithm for patients with chronic pancreatitis (COMBO trial): study protocol for a stepped-wedge cluster-randomized controlled trial
Authors: de Rijk Florence E. M. , van Veldhuisen Charlotte L. , Besselink Marc G. , van Hooft Jeanin E. , van Santvoort Hjalmar C. , van Geenen Erwin J. M. , van Werkhoven Cornelis H. , de Jonge Pieter Jan F. , Bruno Marco J. , Verdonk Robert C. ,   for the Dutch Pancreatitis Study Group
Published: January 2023

Background

Chronic pancreatitis (CP) is an inflammatory disease that may be complicated by abdominal pain, pancreatic dysfunction, nutritional deficiencies, and diminished bone density. Importantly, it is also associated with a substantially impaired quality of life and reduced life expectancy. This may partly be explained by suboptimal treatment, in particular the long-term management of this chronic condition, despite several national and international guidelines. Standardization of care through a structured implementation of guideline recommendations may improve the level of care and lower the complication rate of these patients. Therefore, the aim of the present study is to evaluate to what extent patient education and standardization of care, through the implementation of an evidence-based integrated management algorithm, improve quality of life and reduce pain severity in patients with CP.

Methods

The COMBO trial is a nationwide stepped-wedge cluster-randomized controlled trial. In a stepwise manner, 26 centers, clustered in 6 health regions, cross-over from current practice to care according to an evidence-based integrated management algorithm. During the current practice phase, study participants are recruited and followed longitudinally through questionnaires. Individual patients contribute data to both study periods. Co-primary study endpoints consist of quality of life (assessed by the PANQOLI score) and level of pain (assessed by the Izbicki questionnaire). Secondary outcomes include process measure outcomes, clinical outcomes (e.g., pancreatic function, nutritional status, bone health, interventions, medication use), utilization of healthcare resources, (in) direct costs, and the level of social participation. Standard follow-up is 35 months from the start of the trial.

Discussion

This is the first stepped-wedge cluster-randomized controlled trial to investigate whether an evidence-based integrated therapeutic approach improves quality of life and pain severity in patients with CP as compared with current practice.

Trial registration

ISRCTN, ISRCTN13042622. Registered on 5 September 2020.
TRansfusion strategies in Acute brain INjured patients (TRAIN): a prospective multicenter randomized interventional trial protocol
Authors: Taccone Fabio Silvio , Badenes Rafael , Rynkowski Carla Bittencourt , Bouzat Pierre , Caricato Anselmo , Kurtz Pedro , Moller Kirsten , Diaz Manuel Quintana , Van Der Jagt Mathieu , Videtta Walter , Vincent Jean-Louis
Published: January 2023

Background

Although blood transfusions can be lifesaving in severe hemorrhage, they can also have potential complications. As anemia has also been associated with poor outcomes in critically ill patients, determining an optimal transfusion trigger is a real challenge for clinicians. This is even more important in patients with acute brain injury who were not specifically evaluated in previous large randomized clinical trials. Neurological patients may be particularly sensitive to anemic brain hypoxia because of the exhausted cerebrovascular reserve, which adjusts cerebral blood flow to tissue oxygen demand.

Methods

We described herein the methodology of a prospective, multicenter, randomized, pragmatic trial comparing two different strategies for red blood cell transfusion in patients with acute brain injury: a “liberal” strategy in which the aim is to maintain hemoglobin (Hb) concentrations greater than 9 g/dL and a “restrictive” approach in which the aim is to maintain Hb concentrations greater than 7 g/dL. The target population is patients suffering from traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), or intracerebral hemorrhage (ICH). The primary outcome is the unfavorable neurological outcome, evaluated using the extended Glasgow Outcome Scale (eGOS) of 1–5 at 180 days after the initial injury. Secondary outcomes include, among others, 28-day survival, intensive care unit (ICU) and hospital lengths of stay, the occurrence of extra-cerebral organ dysfunction/failure, and the development of any infection or thromboembolic events. The estimated sample size is 794 patients to demonstrate a reduction in the primary outcome from 50 to 39% between groups (397 patients in each arm). The study was initiated in 2016 in several ICUs and will be completed in December 2022.

Discussion

This trial will assess the impact of a liberal versus conservative strategy of blood transfusion in a large cohort of critically ill patients with a primary acute brain injury. The results of this trial will help to improve blood product and transfusion use in this specific patient population and will provide additional data in some subgroups of patients at high risk of brain ischemia, such as those with intracranial hypertension or cerebral vasospasm.

Trial registration

ClinicalTrials.gov NCT02968654.
Integrative metabolomics of plasma and PBMCs identifies distinctive metabolic signatures in Behçet’s disease
Authors: Park Soo Jin , Park Mi Jin , Park Sun , Lee Eun-So , Lee Do Yup
Published: January 2023

Background

Behçet’s disease (BD) is a systemic inflammatory disease that involves various organs. The clinical manifestation-based diagnosis of BD is a time-consuming process, which makes it difficult to distinguish from patients with similar symptoms. Moreover, an authentic biomarker has not been developed for accurate diagnosis yet. Our current study investigated the unique metabolic signatures of BD and explored biomarkers for precise diagnosis based on an untargeted metabolomic approach.

Methods

Integrative metabolomic and lipidomic profiling was performed on plasma samples of BD patients (n = 40), healthy controls (HCs, n = 18), and disease controls (DCs, n = 17) using GC-TOF MS and LC-Orbitrap MS. Additionally, the lipid profiles of 66 peripheral blood mononuclear cells (PBMCs) were analyzed from 29 BD patients, 18 HCs, and 19 DCs.

Results

Plasma metabolic dysfunction in BD was determined in carbohydrate, hydroxy fatty acid, and polyunsaturated fatty acid metabolisms. A plasma biomarker panel with 13 compounds was constructed, which simultaneously distinguished BD from HC and DC (AUCs ranged from 0.810 to 0.966). Dysregulated PBMC metabolome was signatured by a significant elevation in lysophosphatidylcholines (LPCs) and ether-linked lysophosphatidylethanolamines (EtherLPEs). Ten PBMC-derived lipid composites showed good discrimination power (AUCs ranged from 0.900 to 0.973). Correlation analysis revealed a potential association between disease activity and the metabolites of plasma and PBMC, including sphingosine-1 phosphate and EtherLPE 18:2.

Conclusions

We identified metabolic biomarkers from plasma PBMC, which selectively discriminated BD from healthy control and patients with similar symptoms (recurrent mouth ulcers with/without genital ulcers). The strong correlation was determined between the BD activity and the lipid molecules. These findings may lead to the development for diagnostic and prognostic biomarkers based on a better understanding of the BD pathomechanism.
Sperm DNA methylome abnormalities occur both pre- and post-treatment in men with Hodgkin disease and testicular cancer
Authors: Chan Donovan , Oros Klein Kathleen , Riera-Escamilla Antoni , Krausz Csilla , O’Flaherty Cristian , Chan Peter , Robaire Bernard , Trasler Jacquetta M.
Published: January 2023

Background

Combination chemotherapy has contributed to increased survival from Hodgkin disease (HD) and testicular cancer (TC). However, questions concerning the quality of spermatozoa after treatment have arisen. While studies have shown evidence of DNA damage and aneuploidy in spermatozoa years following anticancer treatment, the sperm epigenome has received little attention. Our objectives here were to determine the impact of HD and TC, as well as their treatments, on sperm DNA methylation. Semen samples were collected from community controls (CC) and from men undergoing treatment for HD or TC, both before initiation of chemotherapy and at multiple times post-treatment. Sperm DNA methylation was assessed using genome-wide and locus-specific approaches.

Results

Imprinted gene methylation was not affected in the sperm of HD or TC men, before or after treatment. Prior to treatment, using Illumina HumanMethylation450 BeadChip (450 K) arrays, a subset of 500 probes was able to distinguish sperm samples from TC, HD and CC subjects; differences between groups persisted post-treatment. Comparing altered sperm methylation between HD or TC patients versus CC men, twice as many sites were affected in TC versus HD men; for both groups, the most affected CpGs were hypomethylated. For TC patients, the promoter region of GDF2 contained the largest region of differential methylation. To assess alterations in DNA methylation over time/post-chemotherapy, serial samples from individual patients were compared. With restriction landmark genome scanning and 450 K array analyses, some patients who underwent chemotherapy showed increased alterations in DNA methylation, up to 2 to 3 years post-treatment, when compared to the CC cohort. Similarly, a higher-resolution human sperm-specific assay that includes assessment of environmentally sensitive regions, or “dynamic sites,” also demonstrated persistently altered sperm DNA methylation in cancer patients post-treatment and suggested preferential susceptibility of “dynamic” CpG sites.

Conclusions

Distinct sperm DNA methylation signatures were present pre-treatment in men with HD and TC and may help explain increases in birth defects reported in recent clinical studies. Epigenetic defects in spermatozoa of some cancer survivors were evident even up to 2 years post-treatment. Abnormalities in the sperm epigenome both pre- and post-chemotherapy may contribute to detrimental effects on future reproductive health.
Genetic, DNA methylation, and immune profile discrepancies between early-stage single primary lung cancer and synchronous multiple primary lung cancer
Authors: Yu Fenglei , Huang Xiaojie , Zhou Danting , Zhao Zhenyu , Wu Fang , Qian Banglun , Wang Qiang , Chen Juan , Liang Qingchun , Jiang Yi , Ding Qi , He Qiongzhi , Tang Jingqun , Wang Xiang , Liu Wenliang , Chen Chen
Published: January 2023

Background

To explore the possible carcinogenesis and help better diagnose and treat patients with synchronous multiple primary lung cancers (sMPLC), we systematically investigated the genetic and DNA methylation profiles of early-stage sMPLC and single primary lung cancer (SPLC) and explored the immune profiles in the tumor microenvironment.

Methods

Hundred and ninety-one patients with 191 nodules in the SPLC group and 132 patients with 295 nodules in the sMPLC group were enrolled. All the samples were subjected to wide panel-genomic sequencing. Genome-wide DNA methylation was assessed using the Infinium Human Methylation 850 K BeadChip. RNA-seq and CIBERSORT analyses were performed to identify the immune characteristics in these two groups.

Results

Lesions from sMPLC patients had lower TMB levels than that from SPLC patients. sMPLC had a similar genetic mutational landscape with SPLC, despite some subgroup genetic discrepancies. Distinct DNA methylation patterns were identified between the two groups. The differentially methylated genes were related to immune response pathways. RNA-seq analyses revealed more immune-related DEGs in sMPLC. Accordingly, more immune-related biological processes and pathways were identified in sMPLC. Aberrant DNA methylation was associated with the abnormal expression of immune-related genes. CIBERSORT analysis revealed the infiltration of immune cells was different between the two groups.

Conclusion

Our study for the first time demonstrated genetic, epigenetic, and immune profile discrepancies between sMPLC and SPLC. Relative to the similar genetic mutational landscape, the DNA methylation patterns and related immune profiles were significantly different between sMPLC and SPLC, indicating their essential roles in the initiation and development of sMPLC.
Large-scale prediction of activity cliffs using machine and deep learning methods of increasing complexity
Authors: Tamura Shunsuke , Miyao Tomoyuki , Bajorath Jürgen
Published: January 2023

Activity cliffs (AC) are formed by pairs of structural analogues that are active against the same target but have a large difference in potency. While much of our knowledge about ACs has originated from the analysis and comparison of compounds and activity data, several studies have reported AC predictions over the past decade. Different from typical compound classification tasks, AC predictions must be carried out at the level of compound pairs representing ACs or nonACs. Most AC predictions reported so far have focused on individual methods or comparisons of two or three approaches and only investigated a few compound activity classes (from 2 to 10). Although promising prediction accuracy has been reported in most cases, different system set-ups, AC definitions, methods, and calculation conditions were used, precluding direct comparisons of these studies. Therefore, we have carried out a large-scale AC prediction campaign across 100 activity classes comparing machine learning methods of greatly varying complexity, ranging from pair-based nearest neighbor classifiers and decision tree or kernel methods to deep neural networks. The results of our systematic predictions revealed the level of accuracy that can be expected for AC predictions across many different compound classes. In addition, prediction accuracy did not scale with methodological complexity but was significantly influenced by memorization of compounds shared by different ACs or nonACs. In many instances, limited training data were sufficient for building accurate models using different methods and there was no detectable advantage of deep learning over simpler approaches for AC prediction. On a global scale, support vector machine models performed best, by only small margins compared to others including simple nearest neighbor classifiers.

Graphical Abstract
Bacterial diversity associated with volatile compound accumulation in pit mud of Chinese strong-flavor baijiu pit
Authors: Shoubao Yan , Yonglei Jia , Qi Zhang , Shunchang Pu , Cuie Shi
Published: January 2023

Pit mud quality is a key parameter that impacts the quality of Chinese strong-flavor Baijiu production.This study was developed to explore spatial bacterial community distributions and the relationships between these distributions and the volatile compound accumulation within the pit mud used in the production of Chinese strong-flavor Baijiu. The results revealed Lactobacillus pasteurii and Limnochorda pilosa were found to be the dominant bacteria present in the upper wall, middle wall, and bottom pit mud layers, whereas the Clostridium genus was detectable at high levels in the lower layer of the pit wall and played a role in contributing to the overall aroma and flavor compounds in produced Chinese strong-flavor Baijiu, with Clostridium abundance being strongly correlated with caproic acid, ethyl caproate, ethyl butyrate, and hexanol levels as well as moderately correlated with butyric acid levels. The abundance of the Lactobacillus genus was positively correlated with levels of ethyl lactate, 1-butanol, and 2,3-butanediol. Limnochorda pilosa was closely associated with ethyl acetate levels. Additionally, the correlations between bacterial communities and chemical properties also investigated, and the results demonstrated PO43−, total carbon, K+, humus, NH4+-N, and Mg2+ levels significantly affected the bacterial community structure of pit mud, and they were positively correlated with the relative abundance of Clostridium. Together, these findings can serve as a foundation for future studies exploring the mechanisms whereby volatile compounds accumulate in different pit mud layers, which facilitates the fermentation regulation and pit mud quality improvement of Chinese strong-flavor Baijiu.
LncRNA–mRNA expression profile and functional network of vascular dysfunction in septic rats
Authors: Han Ye-Chen , Shen Zhu-Jun , Wang Yi-Ning , Xiang Ruo-Lan , Xie Hong-Zhi
Published: January 2023

Background

We used microarrays to analyse the changes in long non-coding RNAs (lncRNAs) and mRNAs in aorta tissue in model rats with lipopolysaccharide-induced sepsis and determined the lncRNA–mRNA and lncRNA–miRNA–mRNA functional networks.

Methods

Wistar rats were intraperitoneally injected with lipopolysaccharide, and the lncRNA and mRNA expression profiles in the aorta were evaluated using microarrays. The functions of the differentially expressed mRNAs were analysed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. We then constructed coding/non-coding co-expression and competing endogenous RNA networks to study the mechanisms related to sepsis in rats.

Results

We identified 503 differentially expressed lncRNAs and 2479 differentially expressed mRNAs in the model rats with lipopolysaccharide-induced sepsis. Mitochondrial fission process 1 (MTFP1) was the most significantly down-regulated mRNA. Bioinformatics analysis showed that the significantly down-regulated mRNAs in the sepsis models were in pathways related to mitochondrial structure, function, and energy metabolism. Coding/non-coding co-expression and competing endogenous RNA analyses were conducted using 12 validated lncRNAs in combination with all mRNAs. The coding/non-coding co-expression analysis showed that the 12 validated lncRNAs were mainly regulatory factors for abnormal energy metabolism, including mitochondrial structure damage and aberrant mitochondrial dynamics. The competing endogenous RNA analysis revealed that the potential functions of these 12 lncRNAs might be related to the inflammatory response.

Conclusion

We determined the differentially expressed lncRNAs and mRNAs in the aorta of septic rats using microarrays. Further studies on these lncRNAs will help elucidate the mechanism of sepsis at the genetic level and may identify potential therapeutic targets.
A remarkably diverse and well-organized virus community in a filter-feeding oyster
Authors: Jiang Jing-Zhe , Fang Yi-Fei , Wei Hong-Ying , Zhu Peng , Liu Min , Yuan Wen-Guang , Yang Li-Ling , Guo Ying-Xiang , Jin Tao , Shi Mang , Yao Tuo , Lu Jie , Ye Ling-Tong , Shi Shao-Kun , Wang Meng , Duan Ming , Zhang Dian-Chang
Published: January 2023

Background

Viruses play critical roles in the marine environment because of their interactions with an extremely broad range of potential hosts. Many studies of viruses in seawater have been published, but viruses that inhabit marine animals have been largely neglected. Oysters are keystone species in coastal ecosystems, yet as filter-feeding bivalves with very large roosting numbers and species co-habitation, it is not clear what role they play in marine virus transmission and coastal microbiome regulation.

Results

Here, we report a Dataset of Oyster Virome (DOV) that contains 728,784 nonredundant viral operational taxonomic unit contigs (≥ 800 bp) and 3473 high-quality viral genomes, enabling the first comprehensive overview of both DNA and RNA viral communities in the oysterCrassostrea hongkongensis. We discovered tremendous diversity among novel viruses that inhabit this oyster using multiple approaches, including reads recruitment, viral operational taxonomic units, and high-quality virus genomes. Our results show that these viruses are very different from viruses in the oceans or other habitats. In particular, the high diversity of novel circoviruses that we found in the oysters indicates that oysters may be potential hotspots for circoviruses. Notably, the viruses that were enriched in oysters are not random but are well-organized communities that can respond to changes in the health state of the host and the external environment at both compositional and functional levels.

Conclusions

In this study, we generated a first “knowledge landscape” of the oyster virome, which has increased the number of known oyster-related viruses by tens of thousands. Our results suggest that oysters provide a unique habitat that is different from that of seawater, and highlight the importance of filter-feeding bivalves for marine virus exploration as well as their essential but still invisible roles in regulating marine ecosystems.
Circular RNA circEMB promotes osteosarcoma progression and metastasis by sponging miR-3184-5p and regulating EGFR expression
Authors: Tan Jianye , Yang Bingsheng , Zhong Haobo , Luo Mengliang , Su Zexin , Xie Chao , Shi Meiling , Sun Chunhan , Lin Lijun
Published: January 2023

Background

Osteosarcoma (OSA) is the most prevalent type of bone cancer with a high rate of metastasis. Circular RNAs (CircRNAs) play an essential role in multiple aspects of tumour biology. This study aimed to elucidate the role of circEMB in OSA.

Methods

circRNAs related to OSA invasion were identified via RNA sequencing and qRT-PCR. The relationship between circEMB levels and clinicopathological features of OSA was examined using the clinical specimens and data of 53 patients with OSA. Several in vivo and in vitro experiments, including intravital imaging, whole-transcriptome sequencing, transwell assay, flow cytometry, dual-luciferase reporter assay, RIP assay, RNA pull-down assay and RNA-FISH, were performed to examine the effects of circEMB on the malignant behaviour of OSA.

Results

A novel circRNA, named circEMB (hsa_circ_001310), was identified in this study. circEMB can promote the malignant behaviour of OSA. In vitro experiments revealed that circEMB knockdown decreased cell proliferation, inhibited tumour invasion and metastasis; increased apoptosis and resulted in G1/S phase arrest. In vivo experiments revealed that circEMB knockdown inhibited tumour growth and metastasis in xenograft-bearing mice. Mechanistically, circEMB affects the malignant behaviour of OSA by mediating EGFR as an miR-3184-5p sponge. In addition, the circEMB/miR-3184-5p/EGFR axis modulates methotrexate (MTX) resistance in OSA.

Conclusions

CircEMB plays a critical role in promoting cancer via the miR-3184-5p/EGFR pathway, indicating that circEMB may serve as a therapeutic target for OSA.
Mortality analysis among sepsis patients in and out of intensive care units using the Japanese nationwide medical claims database: a study by the Japan Sepsis Alliance study group
Authors: Oami Takehiko , Imaeda Taro , Nakada Taka‑aki , Abe Toshikazu , Takahashi Nozomi , Yamao Yasuo , Nakagawa Satoshi , Ogura Hiroshi , Shime Nobuaki , Umemura Yutaka , Matsushima Asako , Fushimi Kiyohide
Published: January 2023

Background

A substantial number of sepsis patients require specialized care, including multidisciplinary care, close monitoring, and artificial organ support in the intensive care unit (ICU). However, the efficacy of ICU management on clinical outcomes remains insufficiently researched. Therefore, we tested the hypothesis that ICU admission would increase the survival rate among sepsis patients.

Methods

We conducted a retrospective study using the nationwide medical claims database of sepsis patients in Japan from 2010 to 2017 with propensity score matching to adjust for baseline imbalances. Patients aged over 20 years, with a combined diagnosis of presumed serious infection and organ failure, were included in this study. The primary outcome studied was the in-hospital mortality among non-ICU and ICU patients. In addition to propensity score matching, we performed a multivariable logistic regression analysis for the primary outcome. As the treatment policy was not extracted from the database, we performed sensitivity analyses to determine mortality differences in adults (20 ≤ age ≤ 64), independent patients, patients without malignant tumors, based on the assumption that treatment intensity is likely to increase in those population.

Results

Among 1,167,901 sepsis patients (974,289 in non-ICU and 193,612 in ICU settings), the unadjusted in-hospital mortality was 22.5% among non-ICU patients and 26.2% among ICU patients (3.7% [95% CI 3.5–3.9]). After propensity score matching, the in-hospital mortality was 29.2% among non-ICU patients and 25.8% among ICU patients ($$-$$-3.4% [95% CI$$-$$-3.7 to$$-$$-3.1]). In-hospital mortality with a multivariable regression analysis ($$-$$-5.0% [95% CI$$-$$-5.2 to$$-$$-4.8]) was comparable with the results of the propensity score matching analysis. In the sensitivity analyses, the mortality differences between non-ICU and ICU in adults, independent patients, and patients without malignant tumors were$$-$$-2.7% [95% CI$$-$$-3.3 to$$-$$-2.2],$$-$$-5.8% [95% CI$$-$$-6.4 to$$-$$-5.2], and$$-$$-1.3% [95% CI$$-$$-1.7 to$$-$$-1.0], respectively.

Conclusions

Herein, using the nationwide medical claims database, we demonstrated that ICU admission was potentially associated with decreasing in-hospital mortality among sepsis patients. Further investigations are warranted to validate these results and elucidate the mechanisms favoring ICU management on clinical outcomes.
The Frail-LESS (LEss Sitting and Sarcopenia in Frail older adults) intervention to improve sarcopenia and maintain independent living via reductions in prolonged sitting: a randomised controlled feasibility trial protocol
Authors: Bailey Daniel P. , Kilbride Cherry , Harper Jamie H. , Victor Christina , Brierley Marsha L. , Hewson David J. , Chater Angel M.
Published: January 2023

Background

Sarcopenia is a progressive and generalised loss of muscle mass and function with advancing age and is a major contributor to frailty. These conditions lead to functional disability, loss of independence, and lower quality of life. Sedentary behaviour is adversely associated with sarcopenia and frailty. Reducing and breaking up sitting should thus be explored as an intervention target for their management. The primary aim of this study, therefore, is to examine the feasibility, safety, and acceptability of conducting a randomised controlled trial (RCT) that evaluates a remotely delivered intervention to improve sarcopenia and independent living via reducing and breaking up sitting in frail older adults.

Methods

This mixed-methods randomised controlled feasibility trial will recruit 60 community-dwelling older adults aged ≥ 65 years with very mild or mild frailty. After baseline measures, participants will be randomised to receive the Frail-LESS (LEss Sitting and Sarcopenia in Frail older adults) intervention or serve as controls (usual care) for 6 months. Frail-LESS is a remotely delivered intervention comprising of tailored feedback on sitting, information on the health risks of excess sitting, supported goal setting and action planning, a wearable device that tracks inactive time and provides alerts to move, health coaching, and peer support. Feasibility will be assessed in terms of recruitment, retention and data completion rates. A process evaluation will assess intervention acceptability, safety, and fidelity of the trial. The following measures will be taken at baseline, 3 months, and 6 months: sitting, standing, and stepping using a thigh-worn activPAL4 device, sarcopenia (via hand grip strength, muscle mass, and physical function), mood, wellbeing, and quality of life.

Discussion

This study will determine the feasibility, safety, and acceptability of evaluating a remote intervention to reduce and break up sitting to support improvements in sarcopenia and independent living in frail older adults. A future definitive RCT to determine intervention effectiveness will be informed by the study findings.

Trial registration

ISRCTN, ISRCTN17158017; Registered 6 August 2021,https://www.isrctn.com/ISRCTN17158017
A hybrid decision support system with golden cut and bipolar q-ROFSs for evaluating the risk-based strategic priorities of fintech lending for clean energy projects
Authors: Wan Qilong , Miao Xiaodong , Wang Chenguang , Dinçer Hasan , Yüksel Serhat
Published: January 2023

In the last decade, the risk evaluation and the investment decision are among the most prominent issues of efficient project management. Especially, the innovative financial sources could have some specific risk appetite due to the increasing return of investment. Hence, it is important to uncover the risk factors of fintech investments and investigate the possible impacts with an integrated approach to the strategic priorities of fintech lending. Accordingly, this study aims to analyze a unique risk set and the strategic priorities of fintech lending for clean energy projects. The most important contributions to the literature can be listed as to construct an impact-direction map of risk-based strategic priorities for fintech lending in clean energy projects and to measure the possible influences by using a hybrid decision making system with golden cut and bipolar q-rung orthopair fuzzy sets. The extension of multi stepwise weight assessment ratio analysis (M-SWARA) is applied for weighting the risk factors of fintech lending. The extension of elimination and choice translating reality (ELECTRE) is employed for constructing and ranking the risk-based strategic priorities for clean energy projects. In this process, data is obtained with the evaluation of three different decision makers. The main superiority of the proposed model by comparing with the previous models in the literature is that significant improvements are made to the classical SWARA method so that a new technique is created with the name of M-SWARA. Hence, the causality analysis between the criteria can also be performed in this proposed model. The findings demonstrate that security is the most critical risk factor for fintech lending system. Moreover, volume is found as the most critical risk-based strategy for fintech lending. In this context, fintech companies need to take some precautions to effectively manage the security risk. For this purpose, the main risks to information technologies need to be clearly identified. Next, control steps should be put for these risks to be managed properly. Furthermore, it has been determined that the most appropriate strategy to increase the success of the fintech lending system is to increase the number of financiers integrated into the system. Within this framework, the platform should be secure and profitable to persuade financiers.
Prescribing pattern of anti-psychotic medications in patients with dementia in Oman: a retrospective observational study
Authors: Al-Rashdi Zainab , Al-Mahrouqi Tamadhir , Al-Shamli Siham , Panchatcharam Sathiya , Al-Busaidi Fatema , Al-Afani Reem , Al-Balushi Naser , Al-Sinawi Hamed
Published: January 2023

Background

Aggression, agitation, psychosis, and sleep disturbances are common behavioral symptoms of people with dementia and they can be distressing for both individuals and their carers. Due to their potential side effects, antipsychotic medications are recommended only for severe behavioral and psychological symptoms of dementia (BPSD). This study explores the prevalence, patterns, and associated factors with antipsychotic drug use among patients with dementia attending geriatric psychiatry services at Sultan Qaboos University Hospital (SQUH). Using a retrospective cross-sectional design, this study examines antipsychotic use among elderly patients aged 60 years or older with dementia who attended geriatric psychiatry services from January 2020 to December 2021. The following information was solicited: socio-demographic factors, type and severity of dementia, presence of co-morbid medical or mental illness, the psychotropic medications prescribed, the anti-psychotic medication use, duration of use, and the indication of use were solicited as well. A multivariate logistic regression analysis was conducted.

Results

The total prevalence of anti-psychotic use among elderly patients with dementia was 56.6%, and among them, 59% were prescribed anti-psychotics for more than 2 years. Being female, having non-Alzheimer’s dementia, experiencing severe stages of dementia, and having other medical or mental co-morbid conditions were independent predictors of antipsychotic drug use (odds ratio [OR] =1.85, confidence interval [CI] =1.04–3.30; OR=2.77, C.I. 1.52–5.04; OR=4.47, C.I. 2.18–9.18; and OR=2.54, C.I. 1.11–5.78, respectively).

Conclusions

Antipsychotic medication use is prevalent among elderly patients with dementia in Oman. The results from this study will help the policymakers and psychiatrists in Oman to plan for the use of non-pharmacological strategies as the first line of management for BPSD.