bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using empirical biological knowledge to infer regulatory networks from multi-omics data
Authors: Pačínková Anna , Popovici Vlad 
Published: August 2022

Abstract
Background
Integration of multi-omics data can provide a more complex view of the biological system consisting of different interconnected molecular components, the crucial aspect for developing novel personalised therapeutic strategies for complex diseases. Various tools have been developed to integrate multi-omics data. However, an efficient multi-omics framework for regulatory network inference at the genome level that incorporates prior knowledge is still to emerge.

Results
We present IntOMICS, an efficient integrative framework based on Bayesian networks. IntOMICS systematically analyses gene expression, DNA methylation, copy number variation and biological prior knowledge to infer regulatory networks. IntOMICS complements the missing biological prior knowledge by so-called empirical biological knowledge, estimated from the available experimental data. Regulatory networks derived from IntOMICS provide deeper insights into the complex flow of genetic information on top of the increasing accuracy trend compared to a published algorithm designed exclusively for gene expression data. The ability to capture relevant crosstalks between multi-omics modalities is verified using known associations in microsatellite stable/instable colon cancer samples. Additionally, IntOMICS performance is compared with two algorithms for multi-omics regulatory network inference that can also incorporate prior knowledge in the inference framework. IntOMICS is also applied to detect potential predictive biomarkers in microsatellite stable stage III colon cancer samples.

Conclusions
We provide IntOMICS, a framework for multi-omics data integration using a novel approach to biological knowledge discovery. IntOMICS is a powerful resource for exploratory systems biology and can provide valuable insights into the complex mechanisms of biological processes that have a vital role in personalised medicine.
Whole-genome sequencing and analysis of Streptomyces strains producing multiple antinematode drugs
Authors: Yi Jeong Sang , Kim Jung Min , Kang Min-Kyoung , Kim Jong Hoon , Cho Hang Su , Ban Yeon Hee , Song Myoung Chong , Son Kwang-Hee , Yoon Yeo Joon 
Published: August 2022

Abstract
Background
Nematodes are parasitic animals that cause over 100 billion US dollars loss in agricultural business. The whole-genomes of two Streptomyces strains, Streptomyces spectabilis KCTC9218T and Streptomyces sp. AN091965, were sequenced. Both strains produce spectinabilin, an antinematode drug. Its secondary metabolism was examined to aid the development of an efficient nematicidal drug-producing host strain.

Results
The whole-genome sequences of S. spectabilis KCTC9218T and Streptomyces sp. AN091965 were analyzed using PacBio and Illumina sequencing platforms, and assembled using hybrid methodology. The total contig lengths for KCTC9218T and AN091965 were 9.97 Mb and 9.84 Mb, respectively. A total of 8,374 and 8,054 protein-coding genes, as well as 39 and 45 secondary metabolite biosynthetic gene clusters were identified in KCTC9218T and AN091965, respectively. 18.4 ± 6.45 mg/L and 213.89 ± 21.30 mg/L of spectinabilin were produced by S. spectabilis KCTC9218T and Streptomyces sp. AN091965, respectively. Pine wilt disease caused by nematode was successfully prevented by lower concentration of spectinabilin injection than that of abamectin recommended by its manufacturer. Production of multiple antinematode drugs, including spectinabilin, streptorubin B, and undecylprodigiosin was observed in both strains using high-resolution liquid chromatography mass spectrometry (LC–MS) analysis.

Conclusions
Whole-genome sequencing of spectinabilin-producing strains, coupled with bioinformatics and mass spectrometry analyses, revealed the production of multiple nematicidal drugs in the KCTC9218T and AN091965 strains. Especially, Streptomyces sp. AN091965 showed high production level of spectinabilin, and this study provides crucial information for the development of potential nematicidal drug producers.
The effect of neostigmine on postoperative delirium after colon carcinoma surgery: a randomized, double-blind, controlled trial
Authors: Liu Fanghao , Lin Xu , Lin Yanan , Deng Xiyuan , Guo Yuwei , Wang Bin , Dong Rui , Bi Yanlin 
Published: August 2022

Abstract
Background
Postoperative delirium (POD) is a critical complication in patients accepting colon carcinoma surgery. Neostigmine, as a cholinesterase inhibitor, can enhance the transmission of cholinergic transmitters in synaptic space, and play an important role in maintaining the normal level of cognition, attention and consciousness. The objective of this study was to investigate the effect of neostigmine on POD and clinical prognosis.

Methods
A randomized, double-blind controlled trial was implemented in Qingdao Municipal Hospital Affiliated to Qingdao University. A total of 454 patients aged 40 to 90 years old accepted colon carcinoma surgery were enrolled between June 7, 2020, and June 7, 2021, with final follow-up on December 8, 2021. Patients were randomly assigned to two groups: the neostigmine group (group N) and the placebo group (group P), the patients in group N were injected with 0.04 mg/kg neostigmine and 0.02 mg/kg atropine intravenously. The primary endpoint was the incidence of POD, researchers evaluated the occurrence of POD by the Confusion Assessment Method (CAM) twice daily (at 10 a.m. and 2 p.m.) during the first 7 postoperative days, POD severity was assessed by the Memorial Delirium Assessment Scale (MDAS). The secondary endpoints were the extubating time, postanesthesia care unit (PACU) time, the incidence of various postoperative complications, length of hospital stays, and 6 months postoperative mortality.

Results
The incidence of POD was 20.20% (81/401), including 19.39% (38/196) in group N and 20.98% (43/205) in group P. There was no significant statistical significance in the incidence of POD between group N and group P (P > 0.05); Compared to group P, the extubating time and PACU time in group N were significantly reduced (P < 0.001), the incidence of postoperative pulmonary complications (POPCs) decreased significantly in group N (P < 0.05), while no significant differences were observed in postoperative hospital stay and mortality in 6 months between the two groups (P > 0.05).

Conclusion
For patients accepted colon carcinoma surgery, neostigmine did not significantly reduce the incidence of POD, postoperative mortality and postoperative hospital stay, while it indeed reduced the extubating time, PACU time and the incidence of POPCs.

Trial registration
The randomized, double-blind, controlled trial was registered retrospectively at www.chictr.org.cn on 07/06/2020 (ChiCTR2000033639).
Control and complications of diabetes in urban primary care units in Thailand: a cross-sectional study
Authors: Puangpet Thanapat , Pongkunakorn Tanyaporn , Chulkarat Nahathai , Bunlangjit Chutikan , Surawit Apinya , Pinsawas Bonggochpass , Mongkolsucharitkul Pichanun , Mayurasakorn Korapat 
Published: August 2022

Abstract
Background
Primary health care system plays a central role in caring for persons with diabetes. Thai National Health Examination Survey (NHES) reports that only 40% of patients with type 2 diabetes mellitus (T2DM) achieve optimal glycemic control. We sought to evaluate the quality of diabetic care (QOC), prevalence of microvascular complications, and associated risk factors among T2DM patients treated at primary care units in urban areas in Thailand.

Methods
A population-based, cross-sectional study of 488 T2DM patients aged over 35 years from 25 primary care units in Samutsakhon, Thailand was conducted during February 2018 to March 2019. Clinical targets of care (TOC) and processes of care (POC) were measured to evaluate QOC. Multivariate logistic regression models were applied to explore the association between risk factors and glycemic control.

Results
41.2% of women and 44.4% of men achieved hemoglobin A1C (A1C) < 53 mmol/mol, while 31.3% of women and 29.7% of men had poor glycemic control (A1C > 63 mmol/mol). 39 participants (8%) achieved all TOC and 318 participants (65.2%) achieved all POC. Significant risk factors for poor glycemic control included diabetes duration > 6 years (AOR = 1.83, 95% CI = 1.20–2.79), being overweight (AOR = 2.54, 95% CI = 1.58–4.08), obesity (AOR = 1.71, 95% CI = 1.05–2.89), triglycerides > 1.7 mmol/l (AOR = 1.81, 95% CI = 1.25–2.78), low density lipoprotein-cholesterol (LDL-C) ≥ 2.6 mmol/l (AOR = 1.55, 95% CI = 1.04–2.28). On the other hand, participants aged > 65 years (AOR = 0.25, 95% CI = 0.14–0.55) or achieved TOC indicators (AOR = 0.69, 95% CI = 0.43–0.89) were significantly associated with glycemic control. Diabetic retinopathy was significantly related to obesity (AOR = 2.21, 95% CI = 1.00–4.86), over waist circumference (AOR = 2.23, 95% CI = 0.77–2.31), and diastolic blood pressure > 90 mmHg (AOR = 1.81, 95% CI = 1.48–1.96).

Conclusion
Access to essential diabetic screening in primary care units is crucial to determine status of disease control and guide disease management. Duration of T2DM, high body mass index, triglyceride and LDL-C were independently associated with poor glycemic control. Obesity was highly associated with diabetes retinopathy. Effort should be taken seriously toward monitoring these factors and providing effective care.
Urine D-ribose levels correlate with cognitive function in community-dwelling older adults
Authors: Zhu Xinyi , Wei Yan , He Yingge , He Rongqiao , Li Juan 
Published: August 2022

Abstract
Background
D-ribose is involved in the pathogenesis of Alzheimer’s Disease. The study aimed to determine the association between D-ribose and cognitive function in a sample of community-dwelling older adults.

Methods
A cross-sectional study was conducted in Chaoyang District, Beijing in 2019–2020. Eligible participants were community-based older adults aged 60 years and above. D-ribose was analyzed from the morning urine. Cognitive function, subjective cognitive decline, and depressive symptoms were measured by a battery of neuropsychological tests. Linear regressions were performed to determine the relationship between the urine D-ribose levels and cognitive performance.

Results
A sample of 1725 participants (67.1% female) aged 60 to 85 years (69.40 ± 5.87 years, mean ± SD) was enrolled in the analysis. The urine D-ribose concentrations ranged from 1.53 to 208.89 μmol/L (median 38.10 μmol/L; interquartile range 22.52—64.96 μmol/L). Higher levels of D-ribose were associated with worse performance on Mini-Mental State Examination and verbal fluency when age, gender, education, depressive symptoms, and cardiovascular risk factors were included as covariates.

Conclusions
The urine D-ribose was negatively correlated with cognitive function in community-dwelling older adults. The findings suggest that the dysmetabolism of D-ribose may play a role at the early stage of cognitive impairment.
Effects of cognitive ageing trajectories on multiple adverse outcomes among Chinese community-dwelling elderly population
Authors: Han Chao , An Jing , Chan Piu 
Published: August 2022

Abstract
Background
Whether cognitive ageing trajectory is related to common functional deficits independent of initial cognitive function remains inconclusive. We aimed to explore the adverse health effect and potential predictive factors of distinct cognitive trajectories among Chinese older adults.

Methods
Three thousand five hundred eighty-one community-dwelling older adults who completed three consecutive cognitive function examinations with the Mini-Mental State Examination (MMSE) over 5 years and were without cognitive impairment at enrollment were included. A group-based trajectory model was used to estimate cognitive ageing trajectories. Multivariable-adjusted odds ratio (OR) and 95% confidence intervals (CI) were computed with logistic regression models to identify potential baseline determinants and health effect of cognitive trajectories on various adverse outcomes.

Results
Two distinct cognitive ageing trajectories were identified with about 5.3% of the study participants ascribed to the rapidly decreasing group. Subjects with rapidly decreasing cognition showed significantly higher odds (OR, 95%CI) of experiencing frailty (4.04, 2.77–5.86), falls (2.01, 1.05–3.70), balance impairment (4.20, 2.75–6.38), high fall risk (5.66, 2.67–11.77) based on the Tinetti total score, disability in activities of daily living (1.76, 1.19–2.56), disability in instrumental activities of daily living (1.52, 1.05–2.19), and motor cognitive risk syndrome (2.24, 1.23–3.98) compared with their steadily decreasing counterparts. Individuals with older age, low education level, no marriage, high score of rapid eye movement behavior disorders, poor physical and cognitive function at baseline were more predisposed to an accelerated cognitive decline.

Conclusions
Faster cognitive decline was independently associated with higher risk of multiple adverse events. Our findings put more emphasis on a routine and constant surveillance of cognitive function among community-dwelling older adults.
The impact of variants and vaccination on the mortality and resource utilization of hospitalized patients with COVID-19
Authors: Stepanova Maria , Lam Brian , Younossi Elena , Felix Sean , Ziayee Mariam , Price Jillian , Pham Huong , de Avila Leyla , Terra Kathy , Austin Patrick , Jeffers Thomas , Escheik Carey , Golabi Pegah , Cable Rebecca , Srishord Manirath , Venkatesan Chapy , Henry Linda , Gerber Lynn , Younossi Zobair M. 
Published: August 2022

Abstract
Background
COVID-19 outcomes among hospitalized patients may have changed due to new variants, therapies and vaccine availability. We assessed outcomes of adults hospitalized with COVID-19 from March 2020–February 2022.

Methods
Data were retrieved from electronic health medical records of adult COVID-19 patients hospitalized in a large community health system. Duration was split into March 2020–June 2021 (pre-Delta period), July–November 2021 (Delta period), and December 2021–February 2022 (Omicron period).

Results
Of included patients (n = 9582), 75% were admitted during pre-Delta, 9% during Delta, 16% during Omicron period. The COVID-positive inpatients were oldest during Omicron period but had lowest rates of COVID pneumonia and resource utilization (p < 0.0001); 46% were vaccinated during Delta and 61% during Omicron period (p < 0.0001). After adjustment for demographics and comorbidities, vaccination was associated with lower inpatient mortality (OR = 0.47 (0.34–0.65), p < 0.0001). The Omicron period was independently associated with lower risk of inpatient mortality (OR = 0.61 (0.45–0.82), p = 0.0010). Vaccination and Omicron period admission were also independently associated with lower healthcare resource utilization (p < 0.05). Magnitudes of associations varied between age groups with strongest protective effects seen in younger patients.

Conclusion
Outcomes of COVID-19 inpatients were evolving throughout the pandemic and were affected by changing demographics, virus variants, and vaccination.

Key point
In this observational study of almost 10,000 patients hospitalized from March 2020–February 2022 with COVID-19, age and having multiple comorbidities remained consistent risk factors for mortality regardless of the variant. Vaccination was high in our hospitalized patients. Vaccination conveyed less severe illness and was associated with lower inpatient mortality.
Determinants of COVID-19 vaccine acceptance in healthcare workers in Iran: National Survey
Authors: Kamali Koorosh , Hoseinzade Zarrintaj , Hajimiri Khadijeh , Hoveidamanesh Soodabeh , Zahraei Seyed Mohsen , Gouya Mohammad Mehdi , Bavandpouri Sousan Mahmoudi , Mohamadi Tahereh , Mohamadi Soraya , Bigdeli Zohre , Maleki Azam , Shirzad Mahboubeh , Heidari Zahra , Farsadegi Mahya , Shoghli Alireza 
Published: August 2022

Abstract
Background and aim
It seems that acceptance of COVID-19 vaccination is the most effective way to tackle the COVID-19 pandemic now. Health care workers (HCWs) are one of the most important groups who are at risk for COVID-19 infection. This study aimed to assess the COVID‐19 vaccine acceptance among HCWs in Iran and its determinants.

Methods
A cross‐sectional survey was carried out among 3600 HCWs in Iran. Data were collected through a self-administered questionnaire by a trained team from February to March 2021. Multi-stage cluster sampling method was used for selecting respondents of the study. Multivariate logistic regression analysis was used to determine the key factors of COVID-19 vaccine acceptance among participants. P-value < 0.05 was considered statistically significant.

Results
Out of the 3536 respondents, 2191 (62.1%) intended to uptake the COVID-19 vaccine. Only about 10 percent of respondents said they did not trust any vaccine (domestic or foreign). Willing to accept a COVID-19 vaccine was relatively high among males, doctors, and those who had a history of hospitalization due to COVID-19 infection. The multivariate regression analysis showed respondents who were 40–50 years (aOR: 1.56; 95% CI: 1.47–1.66), had a history of COVID-19 infection (aOR: 0.85; 95% CI: 0.83–0.88), and hospitalized due to COVID-19 infection (aOR: 2.18; 95% CI: 1.97–2.39), were significantly associated with vaccine acceptance (p < 0.05).

Conclusion
Our study showed moderate acceptance of COVID-19 vaccination in the HCWs in the Islamic Republic of Iran. The most important factor in the acceptance of the COVID-19 vaccine by the health staff is having a history of hospitalization. Further training and justification of health personnel is needed to increase the acceptance of COVID 19 vaccine.
Effectiveness of robot-assisted virtual reality mirror therapy for upper limb motor dysfunction after stroke: study protocol for a single-center randomized controlled clinical trial
Authors: Wei Dong , Hua Xu-Yun , Zheng Mou-Xiong , Wu Jia-Jia , Xu Jian-Guang 
Published: August 2022

AbstractBackgroundUpper limb motor dysfunction is a common sequela of stroke, and its clinical efficacy needs to be improved. This protocol describes a trial to verify the clinical efficacy of robot-assisted virtual reality mirror therapy (RAVRMT) in improving upper limb motor dysfunction in stroke patients, and to explore the central mechanism by using functional magnetic resonance imaging (fMRI).MethodsThis trial will be a single-center, assessor-blinded, randomized controlled clinical study. Thirty-two eligible patients will be randomly divided into 2 groups according to the ratio of 1:1, namely virtual reality mirror therapy (VRMT) group and robot-assisted virtual reality mirror therapy (RAVRMT) group. The interventions will be performed once a day for 4 weeks. Primary outcome is Fugl–Meyer motor function assessment-Upper Extremity (FMA-UE), secondary outcomes are the Montreal Cognitive Assessment (MoCA), activities of daily living (ADL), quality of life (QOL), the pain visual analogue scale (VAS-pain) and fMRI. Adverse events will be recorded, and severe adverse events will be used as criteria to discontinue the intervention.DiscussionCombined application of robot-assisted therapy and virtual reality mirror therapy could theoretically activate mirror neuron system and reward circuits to a greater extent, but further high-quality research is needed. The results of this trial will determine whether RAVRMT could better improve upper limb motor dysfunction after stroke and explore its central mechanism using fMRI.Trial registrationThis trial was prospectively registered at ClinicalTrials.gov (ChiCTR2200061721; 01 July 2022).
A case of Miller Fisher syndrome with delayed onset peripheral facial nerve palsy after COVID-19 vaccination: a case report
Authors: Nanatsue Kentaro , Takahashi Makoto , Itaya Sakiko , Abe Keisuke , Inaba Akira 
Published: August 2022

Abstract
Background
To prevent the spread of the novel coronavirus disease 2019 (COVID-19) infection, various vaccines have been developed and used in a large number of people worldwide. One of the most commonly used vaccines is the mRNA vaccine developed by Moderna. Although several studies have shown this vaccine to be safe, the full extent of its side effects has not yet been known. Miller-Fisher syndrome (MFS) is a rare condition that manifests ophthalmoplegia, ataxia, and loss of tendon reflexes. It is a subtype of Guillain–Barré syndrome and an immune-mediated disease related to serum IgG anti-GQ1b antibodies. Several vaccines including those for COVID-19 have been reported to induce MFS. However, there have been no reports of MFS following Moderna COVID-19 vaccine administration.

Case presentation
A 70-year-old man was referred to our hospital due to diplopia that manifested 1 week after receiving the second Moderna vaccine dose. The patient presented with restricted abduction of both eyes, mild ataxia, and loss of tendon reflexes. He was diagnosed with MFS based on his neurological findings and detection of serum anti-GQ1b antibodies. The patient was administered intravenous immunoglobulin, and his symptoms gradually improved. Five days after admission, the patient showed peripheral facial paralysis on the right side. This symptom was suggested to be a delayed onset of peripheral facial nerve palsy following MFS that gradually improved by administration of steroids and antiviral drugs.

Conclusion
There have been no previous reports of MFS after Moderna COVID-19 vaccination. This case may provide new information about the possible neurological side effects of COVID-19 vaccines.
Time-dependent affective disturbances in abstinent patients with methylphenidate use disorder
Authors: Xu Jie , Zhang Yi , Wang Nan , Sun Pei , Mao Fuqiang , Yuan Ti-Fei 
Published: August 2022

Abstract
Background
Methylphenidate (MPH), also called Ritalin, is used to treat attention-deficit hyperactivity disorder (ADHD) patients. With occasional reports of subjects suffering from Methylphenidate use disorder (MPHUD), few studies analyzed the neuropsychological changes in this population.

Purpose
This study aims to evaluate the clinical outcomes of individuals with MPHUD.

Methods
We retrospectively analyzed 61 MPH patients (aged 16–27 years) admitted to the Beijing Gaoxin Hospital drug rehabilitation program from Jan 2017 to Mar 2019. The drug use history and drug abuse motivation scale were collected at admission. Clinicians rated the Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, and DSM-5 Stimulant use disorder criteria each week during the 4 weeks rehabilitation program. Correlation analyses were conducted between drug use history and affective disturbances.

Results
The results showed that the adolescent period is the peak for MPH exposure, and 1/3 of patients got their first exposure to MPH from their parents. MPH abstinence accompanies severe anxiety and depression symptoms, significantly alleviating after four weeks of treatment.

Conclusions
MPHUD is associated with substantial affective disturbances, which warrants a more considerable sample investigation.