bluuebunny/crossref_metadata_2025 huggingface dataset:
vCOMBAT: a novel tool to create and visualize a computational model of bacterial antibiotic target-binding
Authors: Tran Vi Ngoc-Nha , Shams Alireza , Ascioglu Sinan , Martinecz Antal , Liang Jingyi , Clarelli Fabrizio , Mostowy Rafal , Cohen Ted , Abel zur Wiesch Pia
Published: January 2022

Background

As antibiotic resistance creates a significant global health threat, we need not only to accelerate the development of novel antibiotics but also to develop better treatment strategies using existing drugs to improve their efficacy and prevent the selection of further resistance. We require new tools to rationally design dosing regimens from data collected in early phases of antibiotic and dosing development. Mathematical models such as mechanistic pharmacodynamic drug-target binding explain mechanistic details of how the given drug concentration affects its targeted bacteria. However, there are no available tools in the literature that allow non-quantitative scientists to develop computational models to simulate antibiotic-target binding and its effects on bacteria.

Results

In this work, we have devised an extension of a mechanistic binding-kinetic model to incorporate clinical drug concentration data. Based on the extended model, we develop a novel and interactive web-based tool that allows non-quantitative scientists to create and visualize their own computational models of bacterial antibiotic target-binding based on their considered drugs and bacteria. We also demonstrate how Rifampicin affects bacterial populations of Tuberculosis bacteria using our vCOMBAT tool.

Conclusions

The vCOMBAT online tool is publicly available at https://combat-bacteria.org/.
Divergence of X-linked trans regulatory proteins and the misexpression of gene targets in sterile Drosophila pseudoobscura hybrids
Authors: Go Alwyn C. , Civetta Alberto
Published: January 2022

Background

The genetic basis of hybrid incompatibilities is characterized by pervasive cases of gene interactions. Sex chromosomes play a major role in speciation and X-linked hybrid male sterility (HMS) genes have been identified. Interestingly, some of these genes code for proteins with DNA binding domains, suggesting a capability to act as trans-regulatory elements and disturb the expression of a large number of gene targets. To understand how interactions between trans- and cis-regulatory elements contribute to speciation, we aimed to map putative X-linked trans-regulatory elements and to identify gene targets with disrupted gene expression in sterile hybrids between the subspecies Drosophila pseudoobscura pseudoobscura and D. p. bogotana.

Results

We find six putative trans-regulatory proteins within previously mapped X chromosome HMS loci with sequence changes that differentiate the two subspecies. Among them, the previously characterized HMS gene Overdrive (Ovd) had the largest number of amino acid changes between subspecies, with some substitutions localized within the protein’s DNA binding domain. Using an introgression approach, we detected transcriptional responses associated with a sterility/fertility Ovd allele swap. We found a network of 52 targets of Ovd and identified cis-regulatory effects among target genes with disrupted expression in sterile hybrids. However, a combined analysis of polymorphism and divergence in non-coding sequences immediately upstream of target genes found no evidence of changes in candidate regulatory proximal cis-elements. Finally, peptidases were over-represented among target genes.

Conclusions

We provide evidence of divergence between subspecies within the DNA binding domain of the HMS protein Ovd and identify trans effects on the expression of 52 gene targets. Our results identify a network of trans-cis interactions with possible effects on HMS. This network provides molecular evidence of gene × gene incompatibilities as contributors to hybrid dysfunction.
Reduction of leakage from insertion site during continuous femoral nerve block with catheter-through-needle versus catheter-over-needle technique for postoperative analgesia after total knee arthroplasty: a randomized controlled trial
Authors: Hattammaru Yoshiyasu , Mio Yasushi , Hascilowicz Tomasz , Utsumi Isao , Murakami Yuichi , Omi Sachiko
Published: January 2022

Background

Continuous femoral nerve block (CFNB) is a common procedure used for postoperative analgesia in total knee arthroplasty. Continuous nerve block using a conventional needle (catheter-through-needle/CTN) is complicated by leakage of the anesthetic from the catheter insertion site. A different type of needle (catheter-over-needle/ CON) is now available, which is believed to reduce leakage as the diameter of the catheter is larger than that of the needle. The purpose of this study was to compare the incidence of leakage from the catheter insertion site during CFNB while using CTN and CON for postoperative analgesia after total knee arthroplasty (TKA).

Methods

This prospective, randomized, single-blinded controlled study included 60 patients who were scheduled for TKA at our facility between May 2016 and November 2017. Patients were randomly allocated to the CTN or CON groups. All patients in both groups received CFNB and sciatic nerve block for postoperative analgesia. The administration of 0.16% levobupivacaine mixed with 6 mg of indigo carmine (a dye added to easily identify leakage) was started at 6 ml/h at the end of surgery. The primary outcome was the incidence of leakage from the catheter insertion site. We further investigated the degree of leakage, the incidence of catheter migration, pain scores using the numerical rating scale at 48 h postoperatively, and the number of days until the operated knee could be flexed 120 degrees postoperatively in both groups.

Results

The CON group had a significantly lower incidence and degree of leakage from the catheter insertion site. There were no significant differences in other measurement outcomes.

Conclusions

Use of CON reduces the incidence of leakage from the catheter insertion site during CFNB in the use of postoperative analgesia for total knee arthroplasty. Future research is needed to determine additional benefits of using CON related to decreased leakage.

Trial registration

The study was registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN000021537), prospectively registered on 18 March 2016.
Predictors of preoperative cognitive dysfunction in adults with Moyamoya disease: a preliminary research
Authors: Sun Jian , Shi Zhiyong , Yu Lebao , Wen Yujie , Zhang Dong
Published: January 2022

Objective

To explore potential risk factors of preoperative cognitive dysfunction in adult patients with moyamoya disease (MMD) and discuss significance of moyamoya vessels.

Methods

The author reviewed adult MMD patients harboring no parenchymal infarction or hemorrhage underwent a standardized neuropsychological assessment test battery from December 2018 to May 2019. The authors defined patients with cognitive dysfunction as cognitive impairment shown on 3 or more neuropsychological tests. According to the presence of cerebral angiography, arterial stenosis, moyamoya vessels, and compensatory arteries were conducted. Univariate and multivariate analyses were performed to identify predictors for cognitive dysfunction before surgery. Subgroup analyses by onset type and Suzuki stage were carried out to identify specific predictors for preoperative cognitive dysfunction.

Results

In total, 29 of 92 (31.52%) patients had cognitive dysfunction. Multivariate analysis showed that moyamoya vessels generating from left hemisphere was recognized as independent predictor for cognitive dysfunction (P = 0.025, OR [95%CI], 0.085 [0.012–0.874]). For patients in left ICA-moyamoya subgroup, 19 of 45 (42.22%) cases with sparse moyamoya vessels had cognitive dysfunction (P = 0.031), while 22 (91.67%) of patients with dense moyamoya vessels had normal cognition (P = 0.004). Moyamoya vessels arising from ophthalmic artery had no significant association with cognitive dysfunction (P = 0.111). Multivariate analysis found that moyamoya vessels originating from left ICA was recognized as independent predictors for preoperative cognitive dysfunction (P = 0.048, OR [95%CI], 0.394 [0.132–0.926]).

Conclusions

Moyamoya vessels arising from left hemisphere was a risk factor for the preoperative cognitive dysfunction in adult patients with MMD, with the denser moyamoya vessels, the less cognitive dysfunction. The current study offers a new perspective of moyamoya vessels and supporting data for choosing MMD candidates on cerebral revascularization.
Comparison of pregnancy outcomes and placental characteristics between selective fetal growth restriction with and without thick arterio-arterial anastomosis in monochorionic diamniotic twins
Authors: Wang Xueju , Li Luyao , Yuan Pengbo , Zhao Yangyu , Wei Yuan
Published: January 2022

Background

Unequal placental territory in monochorionic diamniotic twins is a primary cause of selective fetal growth restriction (sFGR), and vascular anastomoses play important role in determining sFGR prognosis. This study investigated differences in placental characteristics and pregnancy outcomes in cases of sFGR with and without thick arterio-arterial anastomosis (AAA).

Methods

A total of 253 patients diagnosed with sFGR between April 2013 and April 2020 were retrospectively analyzed. An AAA greater than 2 mm in diameter was defined as a thick AAA. We compared placental characteristics and pregnancy outcomes between cases of sFGR with and without thick AAA.

Results

Prevalence of AAA, thick arterio-venous anastomosis (AVA), veno-venous anastomosis (VVA), and thick VVA were significantly higher in the thick AAA group relative to the non-thick AAA group (100.0 vs. 78.5%, P < 0.001; 44.3 vs. 15.4%, P < 0.001; 27.1 vs. 10.8%, P = 0.017, and 24.3 vs. 6.2%, P = 0.004, respectively). The total numbers of AVA and total anastomoses were significantly higher in thick AAA group relative to the non-thick AAA group (5 [1, 14] vs. 3 [1, 15, P = 0.016; and 6 [1, 15] vs. 5 [1, 16], P = 0.022, respectively). The total diameter of AAA, AVA, VVA, and all anastomoses in the thick AAA group was larger than in the non-thick AAA group (3.4 [2.0,7.1] vs. 1.4 [0.0, 3.3], P < 0.001; 6.3 [0.3, 12.0] vs. 2.5 [0.3, 17.8], P < 0.001; 4.2±1.8 vs. 1.9±1.2, P =0.004; and 10.7 [3.2,22.4] vs. 4.4 [0.5, 19.3], P < 0.001, respectively). Growth-restricted fetuses in the thick AAA group exhibited significantly increased birthweight relative to those in thenon-thick AAA group (1570 (530, 2460)g vs. 1230 (610, 2480)g, p = 0.002).

Conclusions

In the placentas associated with sFGR, thick AAA can co-occur with thick AVA and VVA, and placental angiogenesis may differ significantly based upon whether or not thick AAA is present. The birth weights of growth-restricted fetuses in cases of sFGR with thick AAA are larger than in cases without thick AAA.
Stabilization of refractive error and associated factors following small incision phacoemulsification cataract surgery
Authors: Khan Ammar M , Waldner Derek M. , Luong Micah , Sanders Emi , Crichton Andrew C. S. , Ford Bryce A.
Published: January 2022

Background

Accumulating evidence suggests that refractive stabilization occurs rapidly following small incision cataract surgery. Nonetheless, many guidelines still suggest waiting four to 6 weeks before prescribing corrective lenses. This study was undertaken to supplement the existing literature regarding refractive stabilization, and evaluate multiple contributing factors that could dissuade clinicians from confidently correcting refractive error in the early post-operative course following routine cataract surgeries.

Methods

Adult patients undergoing phacoemulsification cataract surgery with uncomplicated surgeries and post-surgical courses at the Calgary Ophthalmology Centre (Calgary, Alberta, Canada) were included in this prospective observational case series. Exclusion criteria included known corneal dystrophies, infectious keratitis, complicated surgery or toric/multifocal IOLs. Data was collected at weekly intervals for a total of 6 weeks. Collected data included autorefraction, visual acuity, corneal pachymetry, and effective lens position.

Results

One hundred six eyes of 104 patients were included in this study. Post-operative sphere, cylinder and spherical equivalent were not significantly different at any post-operative week compared with week six, and 80–86% of patients were within 0.5D of last follow-up spherical equivalent at any week. The secondary outcomes of central corneal thickness, effective lens position and visual acuity did, however, exhibit significant differences between early post-operative weeks and last follow-up values.

Conclusions

These data suggest that refractive error can be effectively measured and corrected as early as one-week post-operatively in the majority of patients, though other measures of post-operative stability including central corneal thickness, effective lens position and visual acuity can require up to 4 weeks to stabilize. Thus a conservative and pragmatic approach may be to wait until 4 weeks post-operatively prior to obtaining refractive correction following uncomplicated phacoemulsification cataract surgery.
The Gutenberg health study: a five-year prospective analysis of psychosocial working conditions using COPSOQ (Copenhagen psychosocial questionnaire) and ERI (effort-reward imbalance)
Authors: Nuebling Matthias , Hegewald Janice , Starke Karla Romero , Lincke Hans-Joachim , Jankowiak Sylvia , Liebers Falk , Latza Ute , Letzel Stephan , Riechmann-Wolf Merle , Gianicolo Emilio , Beutel Manfred , Pfeiffer Norbert , Lackner Klaus , Münzel Thomas , Wild Philipp S. , Seidler Andreas
Published: January 2022

Background

Psychosocial working conditions were previously analyzed using the first recruitment wave of the Gutenberg Health Study (GHS) cohort (n = 5000). We aimed to confirm the initial analysis using the entire GHS population at baseline (N = 15,010) and at the five-year follow-up. We also aimed to determine the effects of psychosocial working conditions at baseline on self-rated outcomes measured at follow-up.

Methods

At baseline, working GHS participants were assessed with either the Effort-Reward-Imbalance questionnaire (ERI) (n = 4358) or with the Copenhagen Psychosocial Questionnaire (COPSOQ) (n = 4322); participants still working after five years received the same questionnaire again (ERI n = 3142; COPSOQ n = 3091). We analyzed the association between working conditions and the outcomes job satisfaction, general health, burnout, and satisfaction with life at baseline, at follow-up and also prospectively from baseline to follow-up using linear regression models. We examined the outcome variance explained by the models (R2) to estimate the predictive performance of the questionnaires.

Results

The models’ R2 was comparable to the original baseline analyses at both t0 and t1 (R2 range: ERI 0.10–0.43; COPSOQ 0.10–0.56). However, selected scales of the regression models sometimes changed between assessment times. The prospective analysis showed weaker associations between baseline working conditions and outcomes after five years (R2 range: ERI 0.07–0.19; COPSOQ 0.07–0.24). This was particularly true for job satisfaction. After adjusting for the baseline levels of the outcomes, fewer scales still explained some of the variance in the distribution of the outcome variables at follow-up. The models using only data from t0 or t1 confirmed the previous baseline analysis. We observed a loss of explained variance in the prospective analysis models. This loss was greatest for job satisfaction, suggesting that this outcome is most influenced by short-term working conditions.

Conclusions

Both the COPSOQ and ERI instruments show good criterion validity and adequately predict contemporaneously measured self-reported measurements of health and (occupational) well-being. However, the COPSOQ provides a more detailed picture of working conditions and might be preferable for improvment strategies in workplaces. Additional prospective research with shorter follow-up times would be beneficial for estimating dose-response relationships.
The cost of community outreach HIV interventions: a case study in Thailand
Authors: Soe Kyaw Min , Hauck Katharina , Jiamton Sukhum , Kongsin Sukhontha
Published: January 2022

Background

There was an estimated 440,000 people living with HIV in Thailand in 2018. New cases are declining rapidly thanks to successful prevention programs and scaling up of anti-retroviral therapy (ART). Thailand aims to achieve its commitment to end the HIV epidemic by 2030 and implemented a cascade of HIV interventions through the Reach-Recruit-Test-Treat-Retain (RRTTR) program.

Methods

This study focused on community outreach HIV interventions implemented by Non-Governmental Organizations (NGOs) under the RRTTR program in 27 provinces. We calculated unit cost per person reached for HIV interventions targeted at key-affected populations (KAPs) including men who have sex with men/ transgender (MSM/TG), male sex workers (MSW), female sex workers (FSW), people who inject drugs (PWID) and migrants (MW). We studied program key outputs, costs, and unit costs in variations across different HIV interventions and geographic locations in Thailand. We used these estimates to determine costs of HIV interventions and evaluate economies of scale.

Results

The interventions for migrants in Samut Sakhon was the least costly with a unit cost of 21.6 USD per person to receive services, followed by interventions for migrants in Samut Prakan 23.2 USD per person reached, MSM/TG in Pratum Thani 26.5USD per person reached, MSM/TG in Nonthaburi 26.6 USD per person reached and, MSM/TG in Chon Buri with 26.7 USD per person. The interventions yielded higher efficiency in large metropolitan and surrounding provinces. Harm reduction programs were the costliest compare with other interventions. There was association between unit cost and scale of among interventions indicating the presence of economies scale. Implementing HIV and TB interventions jointly increased efficiency for both cases.

Conclusion

This study suggested that unit cost of community outreach HIV and TB interventions led by CSOs will decrease as they are scaled up. Further studies are suggested to follow up with these ongoing interventions for identifying potential contextual factors to improve efficiency of HIV prevention services in Thailand.
Primary care clinicians’ opinions before and after implementation of cancer screening and prevention clinical decision support in a clinic cluster-randomized control trial: a survey research study
Authors: Harry Melissa L. , Chrenka Ella A. , Freitag Laura A. , Saman Daniel M. , Allen Clayton I. , Asche Stephen E. , Truitt Anjali R. , Ekstrom Heidi L. , O’Connor Patrick J. , Sperl-Hillen Jo Ann M. , Ziegenfuss Jeanette Y. , Elliott Thomas E.
Published: January 2022

Background

Electronic health record (EHR)-linked clinical decision support (CDS) may impact primary care clinicians’ (PCCs’) clinical care opinions. As part of a clinic cluster-randomized control trial (RCT) testing a cancer prevention and screening CDS system with patient and PCC printouts (with or without shared decision-making tools [SDMT]) for patients due for breast, cervical, colorectal, and lung cancer screening and/or human papillomavirus (HPV) vaccination compared to usual care (UC), we surveyed PCCs at study clinics pre- and post-CDS implementation. Our primary aim was to learn if PCCs' opinions changed over time within study arms. Secondary aims including examining whether PCCs' opinions in study arms differed both pre- and post-implementation, and gauging PCCs’ opinions on the CDS in the two intervention arms.

Methods

This study was conducted within a healthcare system serving an upper Midwestern population. We administered pre-implementation (11/2/2017–1/24/2018) and post-implementation (2/2/2020–4/9/2020) cross-sectional electronic surveys to PCCs practicing within a RCT arm: UC; CDS; or CDS + SDMT. Bivariate analyses compared responses between study arms at both time periods and longitudinally within study arms.

Results

Pre-implementation (53%, n = 166) and post-implementation (57%, n = 172) response rates were similar. No significant differences in PCC responses were seen between study arms on cancer prevention and screening questions pre-implementation, with few significant differences found between study arms post-implementation. However, significantly fewer intervention arm clinic PCCs reported being very comfortable with discussing breast cancer screening options with patients compared to UC post-implementation, as well as compared to the same intervention arms pre-implementation. Other significant differences were noted within arms longitudinally. For intervention arms, these differences related to CDS areas like EHR alerts, risk calculators, and ordering screening. Most intervention arm PCCs noted the CDS provided overdue screening alerts to which they were unaware. Few PCCs reported using the CDS, but most would recommend it to colleagues, expressed high CDS satisfaction rates, and thought patients liked the CDS’s information and utility.

Conclusions

While appreciated by PCCs with high satisfaction rates, the CDS may lower PCCs’ confidence regarding discussing patients’ breast cancer screening options and may be used irregularly. Future research will evaluate the impact of the CDS on cancer prevention and screening rates.

Trial registration

clinicaltrials.gov, NCT02986230, December 6, 2016.
Contacts with general practitioners, dentists, and medical specialists among nursing home residents: a cross-sectional study in 44 German nursing homes
Authors: Czwikla Jonas , Schmidt Annika , Schulz Maike , Gerhardus Ansgar , Schmiemann Guido , Wolf-Ostermann Karin , Gand Daniel , Friedrich Anna-Carina , Hoffmann Falk , Rothgang Heinz
Published: January 2022

Background

Nursing home residents have high medical care needs. Their medical care utilization is, however, lower compared to community-dwelling elderly and varies widely among nursing homes. This study quantified the utilization of general practitioners (GPs), dentists, and medical specialists among nursing homes and residents, and investigated whether dentist utilization is associated with individual and nursing home characteristics.

Methods

Forty-four nursing homes invited 2124 residents to participate in a cross-sectional study. For 10 medical specialties, data on contacts in nursing homes, practices, and by telephone in the last 12 months were assessed at individual and nursing home level. The proportion of nursing homes and residents with any form of contact, and the median number and interquartile range (IQR) of contacts among individuals with contact were determined. Using multilevel logistic regression, associations between the probability of individual dental care utilization and sex, age, LTC grade, years of residence, sponsorship, number of nursing home beds, and transport and medical escort services for consultations at a practice were investigated.

Results

The proportion of nursing homes with any form of contact with physicians ranged from 100% for GPs, dentists, and urologists to 76.7% for gynecologists and orthopedists. Among the nursing homes, 442 residents participated (20.8% response). The proportion of residents with any contact varied from 97.8% for GPs, 38.5% for neurologists/psychiatrists, and 32.3% for dentists to 3.0% for gynecologists. Only for GPs, neurologists/psychiatrists, dentists, otorhinolaryngologists, urologists, and dermatologists, the proportion was higher for nursing home contacts than for practice and telephone contacts. Among residents with any contact, the median number of contacts was highest for GPs (11.0 [IQR 7.0-16.0]), urologists (4.0 [IQR 2.0-7.0]), and neurologists/psychiatrists (3.0 [IQR 2.0-5.0]). Dentist utilization varied widely among nursing homes (median odds ratio 2.5) and was associated with higher age.

Conclusions

Almost all residents had regular contact to GPs, but only one third had contact with dentists. Lower proportions with contact were found for medical specialists, except for neurologists/psychiatrists. Reasons for the large variations in dental care utilization among nursing homes should be identified.

Trial registration

DRKS00012383 [2017/12/06].
Facilitating drug delivery in the central nervous system by opening the blood-cerebrospinal fluid barrier with a single low energy shockwave pulse
Authors: Kung Yi , Chen Kuan-Yu , Liao Wei-Hao , Hsu Yi-Hua , Wu Chueh-Hung , Hsiao Ming-Yen , Huang Abel P.-H. , Chen Wen-Shiang
Published: January 2022

Background

The blood-cerebrospinal fluid (CSF) barrier (BCSFB) is critically important to the pathophysiology of the central nervous system (CNS). However, this barrier prevents the safe transmission of beneficial drugs from the blood to the CSF and thus the spinal cord and brain, limiting their effectiveness in treating a variety of CNS diseases.

Methods

This study demonstrates a method on SD rats for reversible and site-specific opening of the BCSFB via a noninvasive, low-energy focused shockwave (FSW) pulse (energy flux density 0.03 mJ/mm2) with SonoVue microbubbles (2 × 106 MBs/kg), posing a low risk of injury.

Results

By opening the BCSFB, the concentrations of certain CNS-impermeable indicators (70 kDa Evans blue and 500 kDa FITC-dextran) and drugs (penicillin G, doxorubicin, and bevacizumab) could be significantly elevated in the CSF around both the brain and the spinal cord. Moreover, glioblastoma model rats treated by doxorubicin with this FSW-induced BCSFB (FSW-BCSFB) opening technique also survived significantly longer than untreated controls.

Conclusion

This is the first study to demonstrate and validate a method for noninvasively and selectively opening the BCSFB to enhance drug delivery into CSF circulation. Potential applications may include treatments for neurodegenerative diseases, CNS infections, brain tumors, and leptomeningeal carcinomatosis.
LncRNA NORAD facilitates oral squamous cell carcinoma progression by sponging miR-577 to enhance TPM4
Authors: Qi Change , Liu Jianwei , Guo Pengnv , Xu Yali , Hu Jing , Han Xiaomei
Published: January 2022

Background

Long non-coding RNAs (lncRNAs) have been reported to be vital factors to affect the expression of genes and proteins. Also, it has been proved that the abnormal expression or mutation of lncRNAs stands as a signal of metastasis and proliferation of cancer. Nevertheless, the majority of lncRNAs still need to be explored in abundant cancers especially in oral squamous cell carcinoma (OSCC).

Methods

RT-qPCR assays were applied to test the expression of RNAs. Mechanism assays were performed to verify the combination among NORAD, TPM4 and miR-577. Also, functional assays were conducted to verify the function of RNAs on OSCC cells.

Results

LncRNA NORAD was highly expressed in OSCC tissues and cells. NORAD silencing repressed the biological behaviors of OSCC cells. MiR-577 was found in OSCC with low expression, and RIP assays illustrated that NORAD, miR-577 and TPM4 coexisted in RNA-induced silencing complexes. Rescue assays proved that the overexpression of TPM4 could recover the effect of NORAD silencing on OSCC progression.

Conclusions

It was revealed that NORAD functioned as a tumor promoter to sponge miR-577 thus elevating TPM4 in OSCC, which indicated that NORAD was worthy to be studied as a target for the treatment of OSCC.
Association analysis of SOCS3, JAK2 and STAT3 gene polymorphisms and genetic susceptibility to type 2 diabetes mellitus in Chinese population
Authors: Zhang Yang , Lin Chunwen , Chen Rong , Luo Ling , Huang Jialu , Liu Hao , Chen Weiying , Xu Jian , Yu Haibing , Ding Yuanlin
Published: January 2022

Aim

The association of polymorphisms in the three genes of SOCS3, JAK2 and STAT3 with genetic susceptibility to type 2 diabetes mellitus (T2DM) was explored, and its interaction with environmental factors such as hypertension and triglycerides was analyzed.

Methods

The Hardy–Weinberg balance test was used to analyze the random balance of genes in the population. The analysis of the association of SNPs with T2DM was performed using Pearson’s chi-square test. Haplotype frequency distribution, SNPs-SNPs interaction and environmental factors were analyzed by chi-square test and logistic regression.

Results

The genotype distribution of SNPs rs2280148 of the SOCS3 gene was statistically significant. The allele frequency distribution of SNPs (rs4969168/rs2280148) was statistically different. After covariate correction, the SOCS3 gene locus (rs4969168) showed an association with T2DM in additive model, while the rs2280148 locus showed an association with T2DM in all three models. The locus (rs10974914/rs10815157) allele and genotype frequency distribution of JAK2 were statistically significant. After covariate correction, two SNPs in the gene showed association with T2DM in both additive and recessive models. The distribution of genotype frequencies of SNPs rs1053005 locus in gene STAT3 was statistically significant between the two groups. In recessive genetic models, rs1053005 locus polymorphisms was associated with T2DM. Haplotype S3 (G G)/S 4 (G T) of the SOCS3 gene as well as haplotype J2 (A G)/J 3 (G C) of the JAK2 gene were closely associated with T2DM. There was an interaction between SNPs rs4969168 and SNPs rs2280148 in the SOCS3 gene. There was an interaction between the SOCS3, JAK2 and STAT3 genes and hypertension/triglycerides.

Conclusion

The SOCS3 and JAK2 genes may be associated with T2DM in the Chinese population, in which SNPs carrying the A allele (rs4969168)/G allele (rs2280148)/C allele (rs10815157) have a reduced risk of T2DM. Haplotype S3 (G G)/S 4 (G T) of the SOCS3 gene and haplotype J2 (A G)/J 3 (G C) of the JAK2 gene may be influencing factor for T2DM. The interaction between SNPs rs4969168 and SNPs rs2280148 increases the risk of T2DM. Hypertension and triglycerides may interact with SNPs of T2DM susceptibility genes.
Myxopyronin B inhibits growth of a Fidaxomicin-resistant Clostridioides difficile isolate and interferes with toxin synthesis
Authors: Brauer Madita , Herrmann Jennifer , Zühlke Daniela , Müller Rolf , Riedel Katharina , Sievers Susanne
Published: January 2022

The anaerobic, gastrointestinal pathogenClostridioides difficilecan cause severe forms of enterocolitis which is mainly mediated by the toxins it produces. The RNA polymerase inhibitor Fidaxomicin is the current gold standard for the therapy ofC. difficile infections due to several beneficial features including its ability to suppress toxin synthesis inC. difficile. In contrast to the Rifamycins, Fidaxomicin binds to the RNA polymerase switch region, which is also the binding site for Myxopyronin B. Here, serial broth dilution assays were performed to test the susceptibility ofC. difficileand other anaerobes to Myxopyronin B, proving that the natural product is considerably active againstC. difficileand that there is no cross-resistance between Fidaxomicin and Myxopyronin B in a Fidaxomicin-resistantC. difficilestrain. Moreover, mass spectrometry analysis indicated that Myxopyronin B is able to suppress early phase toxin synthesis inC. difficileto the same degree as Fidaxomicin. Conclusively, Myxopyronin B is proposed as a new lead structure for the design of novel antibiotics for the therapy ofC. difficileinfections.
The effect of exercise on cytokines: implications for musculoskeletal health: a narrative review
Authors: Docherty Sophie , Harley Rachael , McAuley Joseph J. , Crowe Lindsay A. N. , Pedret Carles , Kirwan Paul D. , Siebert Stefan , Millar Neal L.
Published: January 2022

The physiological effects of physical exercise are ubiquitously reported as beneficial to the cardiovascular and musculoskeletal systems. Exercise is widely promoted by medical professionals to aid both physical and emotional wellbeing; however, mechanisms through which this is achieved are less well understood. Despite numerous beneficial attributes, certain types of exercise can inflict significant significant physiological stress. Several studies document a key relationship between exercise and immune activation. Activation of the innate immune system occurs in response to exercise and it is proposed this is largely mediated by cytokine signalling. Cytokines are typically classified according to their inflammatory properties and evidence has shown that cytokines expressed in response to exercise are diverse and may act to propagate, modulate or mitigate inflammation in musculoskeletal health. The review summarizes the existing literature on the relationship between exercise and the immune system with emphasis on how exercise-induced cytokine expression modulates inflammation and the immune response.
Quality of life and cost consequence of delays in endovascular treatment for acute ischemic stroke in China
Authors: Ni Weiyi , Kunz Wolfgang G. , Goyal Mayank , Chen Lijin , Jiang Yawen
Published: January 2022

Background

Although endovascular therapy (EVT) improves clinical outcomes in patients with acute ischemic stroke, the time of EVT initiation significantly influences clinical outcomes and healthcare costs. This study evaluated the impact of EVT treatment delay on cost-effectiveness in China.

Methods

A model combining a short-term decision tree and long-term Markov health state transition matrix was constructed. For each time window of symptom onset to EVT, the probability of receiving EVT or non-EVT treatment was varied, thereby varying clinical outcomes and healthcare costs. Clinical outcomes and cost data were derived from clinical trials and literature. Incremental cost-effectiveness ratio and incremental net monetary benefits were simulated. Deterministic and probabilistic sensitivity analyses were performed to assess the robustness of the model. The willingness-to-pay threshold per quality-adjusted life-year (QALY) was set to ¥71,000 ($10,281).

Results

EVT performed between 61 and 120 min after the stroke onset was most cost-effective comparing to other time windows to perform EVT among AIS patients in China, with an ICER of ¥16,409/QALY ($2376) for performing EVT at 61–120 min versus the time window of 301–360 min. Each hour delay in EVT resulted in an average loss of 0.45 QALYs and 165.02 healthy days, with an average net monetary loss of ¥15,105 ($2187).

Conclusions

Earlier treatment of acute ischemic stroke patients with EVT in China increases lifetime QALYs and the economic value of care without any net increase in lifetime costs. Thus, healthcare policies should aim to improve efficiency of pre-hospital and in-hospital workflow processes to reduce the onset-to-puncture duration in China.
φYeO3-12 phage tail fiber Gp17 as a promising high specific tool for recognition of Yersinia enterocolitica pathogenic serotype O:3
Authors: Filik Karolina , Szermer-Olearnik Bożena , Niedziółka-Jönson Joanna , Roźniecka Ewa , Ciekot Jarosław , Pyra Anna , Matyjaszczyk Irwin , Skurnik Mikael , Brzozowska Ewa
Published: January 2022

Yersiniosis is an infectious zoonotic disease caused by two enteropathogenic species of Gram-negative genus Yersinia: Yersinia enterocolitica and Yersinia pseudotuberculosis. Pigs and other wild and domestic animals are reservoirs for these bacteria. Infection is usually spread to humans by ingestion of contaminated food. Yersiniosis is considered a rare disease, but recent studies indicate that it is overlooked in the diagnostic process therefore the infections with this bacterium are not often identified. Reliable diagnosis of Yersiniosis by culturing is difficult due to the slow growth of the bacteria easily overgrown by other more rapidly growing microbes unless selective growth media is used. Phage adhesins recognizing bacteria in a specific manner can be an excellent diagnostic tool, especially in the diagnosis of pathogens difficult for culturing. In this study, it was shown that Gp17, the tail fiber protein (TFP) of phage φYeO3-12, specifically recognizes only the pathogenic Yersinia enterocolitica serotype O:3 (YeO:3) bacteria. The ELISA test used in this work confirmed the specific interaction of this protein with YeO:3 and demonstrated a promising tool for developing the pathogen recognition method based on phage adhesins.
Reducing infantile anemia: insight on patterns of process and outcome indicators by ethnicity and socioeconomic class during a 10-year intervention program and 5 years after
Authors: Meyerovitch Joseph , Carmi Doron , Aviner Shraga , Sherf Michael , Comaneshter Doron , Laks Yoseph , Key Calanit , Gabbay Uri , Cohen Arnon D.
Published: January 2022

Background

In 2005, Clalit Health Services (CHS), the largest health maintenance organization in Israel, initiated an intervention program aimed at reducing the prevalence rate of infantile anemia (IA). This study evaluated the progress made during the intervention (2005–2014) and its yield 5 years after it ended (2019).

Methods

The CHS database was retrospectively reviewed twice yearly from 2005 to 2014 for repetitive samples of children aged 9 to 18 months regarding the previous half-year interval, and a single sample in 2019. Data were collected on gender, ethnicity (Jewish/non-Jewish), socioeconomic class (SEC; low/intermediate/high), hemoglobin testing (yes/no), and hemoglobin level (if tested). Excluded were infants with documented or suspected hemoglobinopathy.

Results

At study initiation, the rate of performance of hemoglobin testing was 54.7%, and the IA prevalence rate was 7.8%. The performance rate was lower in the Jewish than the non-Jewish subpopulation. The low-SEC subpopulation had a similar hemoglobin testing rate to the high-SEC subpopulation but double the IA prevalence rate. Overall, by the end of the intervention (2014), the performance rate increased to 87.5%, and the AI prevalence rate decreased to 3.4%. In 2019, there was little change in the performance rate from the end of the intervention (88%) and the IA prevalence was further reduced to 2.7%. The non-Jewish and low-SEC subpopulations showed the most improvement which was maintained and even bettered 5 years after the intervention ended.

Conclusions

The 10-year IA intervention program introduced by CHS in 2005 led to a reduction in IA prevalence rate to about 3.5% in all sub-populations evaluated. By program end, the results in the weaker subpopulations, which had the highest prevalence of IA at baseline, were not inferior to those in the stronger subpopulations. We recommended to the Israel Ministry of Health to adopt the intervention countrywide, and we challenge other countries to consider similar interventions.
Hepatocyte generation in liver homeostasis, repair, and regeneration
Authors: Pu Wenjuan , Zhou Bin
Published: January 2022

The liver has remarkable capability to regenerate, employing mechanism to ensure the stable liver-to-bodyweight ratio for body homeostasis. The source of this regenerative capacity has received great attention over the past decade yet still remained controversial currently. Deciphering the sources for hepatocytes provides the basis for understanding tissue regeneration and repair, and also illustrates new potential therapeutic targets for treating liver diseases. In this review, we describe recent advances in genetic lineage tracing studies over liver stem cells, hepatocyte proliferation, and cell lineage conversions or cellular reprogramming. This review will also evaluate the technical strengths and limitations of methods used for studies on hepatocyte generation and cell fate plasticity in liver homeostasis, repair and regeneration.
Personal identification with artificial intelligence under COVID-19 crisis: a scoping review
Authors: Matsuda Shinpei , Yoshimura Hitoshi
Published: January 2022

Background

Artificial intelligence is useful for building objective and rapid personal identification systems. It is important to research and develop personal identification methods as social and institutional infrastructure. A critical consideration during the coronavirus disease 2019 pandemic is that there is no contact between the subjects and personal identification systems. The aim of this study was to organize the recent 5-year development of contactless personal identification methods that use artificial intelligence.

Methods

This study used a scoping review approach to map the progression of contactless personal identification systems using artificial intelligence over the past 5 years. An electronic systematic literature search was conducted using the PubMed, Web of Science, Cochrane Library, CINAHL, and IEEE Xplore databases. Studies published between January 2016 and December 2020 were included in the study.

Results

By performing an electronic literature search, 83 articles were extracted. Based on the PRISMA flow diagram, 8 eligible articles were included in this study. These eligible articles were divided based on the analysis targets as follows: (1) face and/or body, (2) eye, and (3) forearm and/or hand. Artificial intelligence, including convolutional neural networks, contributed to the progress of research on contactless personal identification methods.

Conclusions

This study clarified that contactless personal identification methods using artificial intelligence have progressed and that they have used information obtained from the face and/or body, eyes, and forearm and/or hand.
Indicators for the optimization of sustainable urban energy systems based on energy system modeling
Authors: Klemm Christian , Wiese Frauke
Published: January 2022

Background

Urban energy systems are responsible for 75% of the world’s energy consumption and for 70% of the worldwide greenhouse gas emissions. Energy system models are used to optimize, benchmark and compare such energy systems with the help of energy sustainability indicators. We discuss several indicators for their basic suitability and their response to changing boundary conditions, system structures and reference values. The most suitable parameters are applied to four different supply scenarios of a real-world urban energy system.

Results

There is a number of energy sustainability indicators, but not all of them are suitable for the use in urban energy system optimization models. Shortcomings originate from the omission of upstream energy supply chains (secondary energy efficiency), from limited capabilities to compare small energy systems (energy productivity), from excessive accounting expense (regeneration rate), from unsuitable accounting methods (primary energy efficiency), from a questionable impact of some indicators on the overall system sustainability (self-sufficiency), from the lack of detailed information content (share of renewables), and more. On the other hand, indicators of absolute greenhouse gas emissions, energy costs, and final energy demand are well suitable for the use in optimization models. However, each of these indicators only represents partial aspects of energy sustainability; the use of only one indicator in the optimization process increases the risk that other important aspects will deteriorate significantly, eventually leading to suboptimal or even unrealistic scenarios in practice. Therefore, multi-criteria approaches should be used to enable a more holistic optimization and planning of sustainable urban energy systems.

Conclusion

We recommend multi-criteria optimization approaches using the indicators of absolute greenhouse gas emissions, absolute energy costs, and absolute energy demand. For benchmarking and comparison purposes, specific indicators should be used and therefore related to the final energy demand, respectively, the number of inhabitants. Our example scenarios demonstrate modeling strategies to optimize sustainability of urban energy systems.
Spatial distribution of above ground carbon density in Harana Forest, Ethiopia
Authors: Bedane Girma Ayele , Feyisa Gudina Legese , Senbeta Feyera
Published: January 2022

Background

The need for understanding spatial distribution of forest aboveground carbon density (ACD) has increased to improve management practices of forest ecosystems. This study examined spatial distribution of the ACD in the Harana Forest. A grid sampling technique was employed and three nested circular plots were established at each point where grids intersected. Forest-related data were collected from 1122 plots while the ACD of each plot was estimated using the established allometric equation. Environmental variables in raster format were downloaded from open sources and resampled into a spatial resolution of 30 m. Descriptive statistics were computed to summarize the ACD. A Random Forest classification model in the R-software package was used to select strong predictors, and to predict the spatial distribution of ACD.

Results

The mean ACD was estimated at 131.505 ton per ha in this study area. The spatial prediction showed that the high class of the ACD was confined to eastern and southwest parts of the Harana Forest. The Moran’s statistics depicted similar observations showing the higher clustering of ACD in the eastern and southern parts of the study area. The higher ACD clustering was linked with the higher species richness, species diversity, tree density, tree height, clay content, and SOC. Conversely, the lower ACD clustering in the Harana Forest was associated with higher soil cation exchange capacity, silt content, and precipitation.

Conclusions

The spatial distribution of ACD in this study area was mainly influenced by attributes of the forest stand and edaphic factors in comparison to topographic and climatic factors. Our findings could provide basis for better management and conservation of aboveground carbon storage in the Harana Forest, which may contribute to Ethiopia’s strategy of reducing carbon emission.
Prevalence of marijuana use in pregnant women with concurrent opioid use disorder or alcohol use in pregnancy
Authors: Page Kimberly , Murray-Krezan Cristina , Leeman Lawrence , Carmody Mary , Stephen Julia M. , Bakhireva Ludmila N.
Published: January 2022

Background

A quarter of pregnant women use alcohol, 6.5/1000 deliveries are affected by opioid use disorder (OUD), and the prevalence of cannabis use in pregnant women is increasing. However, marijuana co-exposure in polysubstance-using women is not well described.

Methods

The well-characterized ENRICH-1 cohort (n = 251), which focused on the effects of two primary exposures of interest—opioids and alcohol, was used to (1) estimate the prevalence/frequency of marijuana use in those with OUD and/or alcohol use, and (2) examined correlates of marijuana use. Participants were classified into an OUD group (n = 125), Alcohol group (n = 69), and concurrent OUD and Alcohol (OUD + Alcohol) group (n = 57). Self-report and biomarkers ascertained substance use. Multivariable logistic regression identified correlates of marijuana use.

Results

The prevalence of any marijuana use in pregnancy was 43.2%, 52.6%, and 46.4% in the OUD, OUD + Alcohol, and Alcohol groups, respectively. Correspondingly, weekly or daily use was reported by 19.4%, 21.0%, and 24.6% of participants. In the OUD and OUD + Alcohol groups, the proportion of women using marijuana was significantly higher in those taking buprenorphine (45.8% and 58.3%, respectively) compared to women using methadone (37.5% and 42.9%, respectively). Mean maternal age was lower in women who used marijuana in all three groups compared to non-marijuana users. Independent correlates of marijuana use (controlling for group, race/ethnicity, education, and smoking) were maternal age (adjusted Odds Ratio (aOR) per 5-year increment 0.61; (95% CI 0.47, 0.79)), and polysubstance use (aOR 2.02; 95% CI 1.11, 3.67). There was a significant interaction between partnership status and group: among women who were not in a partnership, those in the OUD and OUD + Alcohol groups had lower odds of marijuana use relative to the Alcohol group. For women in the Alcohol group, partnered women had lower odds of marijuana use than un-partnered women (aOR 0.12; 95% CI: 0.02, 0.68).

Conclusions

Results indicate a relatively high prevalence and frequency of marijuana use in pregnant women being treated for OUD and/or women consuming alcohol while pregnant. These results highlight the need for ongoing risk reduction strategies addressing marijuana use for pregnant women receiving OUD treatment and those with alcohol exposure.