bluuebunny/crossref_metadata_2025 huggingface dataset:
GenoMycAnalyzer: a web-based tool for species and drug resistance prediction for Mycobacterium genomes
Authors: Kim Doyoung , Shin Jeong-Ih , Yoo In Young , Jo Sungjin , Chu Jiyon , Cho Woo Young , Shin Seung-Hun , Chung Yeun-Jun , Park Yeon-Joon , Jung Seung-Hyun
Published: April 2024

Background

Drug-resistant tuberculosis (TB) is a major threat to global public health. Whole-genome sequencing (WGS) is a useful tool for species identification and drug resistance prediction, and many clinical laboratories are transitioning to WGS as a routine diagnostic tool. However, user-friendly and high-confidence automated bioinformatics tools are needed to rapidly identify M. tuberculosis complex (MTBC) and non-tuberculous mycobacteria (NTM), detect drug resistance, and further guide treatment options.

Results

We developed GenoMycAnalyzer, a web-based software that integrates functions for identifying MTBC and NTM species, lineage and spoligotype prediction, variant calling, annotation, drug-resistance determination, and data visualization. The accuracy of GenoMycAnalyzer for genotypic drug susceptibility testing (gDST) was evaluated using 5,473 MTBC isolates that underwent phenotypic DST (pDST). The GenoMycAnalyzer database was built to predict the gDST for 15 antituberculosis drugs using the World Health Organization mutational catalogue. Compared to pDST, the sensitivity of drug susceptibilities by the GenoMycAnalyzer for first-line drugs ranged from 95.9% for rifampicin (95% CI 94.8–96.7%) to 79.6% for pyrazinamide (95% CI 76.9–82.2%), whereas those for second-line drugs ranged from 98.2% for levofloxacin (95% CI 90.1–100.0%) to 74.9% for capreomycin (95% CI 69.3–80.0%). Notably, the integration of large deletions of the four resistance-conferring genes increased gDST sensitivity. The specificity of drug susceptibilities by the GenoMycAnalyzer ranged from 98.7% for amikacin (95% CI 97.8–99.3%) to 79.5% for ethionamide (95% CI 76.4–82.3%). The incorporated Kraken2 software identified 1,284 mycobacterial species with an accuracy of 98.8%. GenoMycAnalyzer also perfectly predicted lineages for 1,935 MTBC and spoligotypes for 54 MTBC.

Conclusions

GenoMycAnalyzer offers both web-based and graphical user interfaces, which can help biologists with limited access to high-performance computing systems or limited bioinformatics skills. By streamlining the interpretation of WGS data, the GenoMycAnalyzer has the potential to significantly impact TB management and contribute to global efforts to combat this infectious disease. GenoMycAnalyzer is available at http://www.mycochase.org.
Decoding the role of oxidative stress resistance and alternative carbon substrate assimilation in the mature biofilm growth mode of Candida glabrata
Authors: Raj Khem , Paul Dhiraj , Rishi Praveen , Shukla Geeta , Dhotre Dhiraj , YogeshSouche
Published: April 2024

Background

Biofilm formation is viewed as a vital mechanism in C. glabrata pathogenesis. Although, it plays a significant role in virulence but transcriptomic architecture and metabolic pathways governing the biofilm growth mode of C. glabrata remain elusive. The present study intended to investigate the genes implicated in biofilm growth phase of C. glabrata through global transcriptomic approach.

Results

Functional analysis of Differentially expressed genes (DEGs) using gene ontology and pathways analysis revealed that upregulated genes are involved in the glyoxylate cycle, carbon-carbon lyase activity, pre-autophagosomal structure membrane and vacuolar parts whereas, down- regulated genes appear to be associated with glycolysis, ribonucleoside biosynthetic process, ribosomal and translation process in the biofilm growth condition. The RNA-Seq expression of eight selected DEGs (CgICL1, CgMLS1, CgPEP1, and CgNTH1, CgERG9, CgERG11, CgTEF3, and CgCOF1) was performed with quantitative real-time PCR (RT-qPCR). The gene expression profile of selected DEGs with RT-qPCR displayed a similar pattern of expression as observed in RNA-Seq. Phenotype screening of mutant strains generated for genes CgPCK1 and CgPEP1, showed that Cgpck1∆ failed to grow on alternative carbon substrate (Glycerol, Ethanol, Oleic acid) and similarly, Cgpep1∆ unable to grow on YPD medium supplemented with hydrogen peroxide. Our results suggest that in the absence of glucose, C. glabrata assimilate glycerol, oleic acid and generate acetyl coenzyme-A (acetyl-CoA) which is a central and connecting metabolite between catabolic and anabolic pathways (glyoxylate and gluconeogenesis) to produce glucose and fulfil energy requirements.

Conclusions

The study was executed using various approaches (transcriptomics, functional genomics and gene deletion) and it revealed that metabolic plasticity of C. glabrata (NCCPF-100,037) in biofilm stage modulates its virulence and survival ability to counter the stress and may promote its transition from commensal to opportunistic pathogen. The observations deduced from the present study along with future work on characterization of the proteins involved in this intricate process may prove to be beneficial for designing novel antifungal strategies.
Association between triglyceride glucose and acute kidney injury in patients with acute myocardial infarction: a propensity score‑matched analysis
Authors: Cai Dabei , Xiao Tingting , Chen Qianwen , Gu Qingqing , Wang Yu , Ji Yuan , Sun Ling , Wei Jun , Wang Qingjie
Published: April 2024

Background

Acute kidney injury (AKI) in patients with acute myocardial infarction (AMI) often indicates a poor prognosis.

Objective

This study aimed to investigate the association between the TyG index and the risk of AKI in patients with AMI.

Methods

Data were taken from the Medical Information Mart for Intensive Care (MIMIC) database. A 1:3 propensity score (PS) was set to match patients in the AKI and non-AKI groups. Multivariate logistic regression analysis, restricted cubic spline (RCS) regression and subgroup analysis were performed to assess the association between TyG index and AKI.

Results

Totally, 1831 AMI patients were included, of which 302 (15.6%) had AKI. The TyG level was higher in AKI patients than in non-AKI patients (9.30 ± 0.71 mg/mL vs. 9.03 ± 0.73 mg/mL, P < 0.001). Compared to the lowest quartile of TyG levels, quartiles 3 or 4 had a higher risk of AKI, respectively (Odds Ratiomodel 4 = 2.139, 95% Confidence Interval: 1.382–3.310, for quartile 4 vs. quartile 1, Ptrend < 0.001). The risk of AKI increased by 34.4% when the TyG level increased by 1 S.D. (OR: 1.344, 95% CI: 1.150–1.570, P < 0.001). The TyG level was non-linearly associated with the risk of AKI in the population within a specified range. After 1:3 propensity score matching, the results were similar and the TyG level remained a risk factor for AKI in patients with AMI.

Conclusion

High levels of TyG increase the risk of AKI in AMI patients. The TyG level is a predictor of AKI risk in AMI patients, and can be used for clinical management.
Tailoring remote patient management in cardiovascular risk management for healthcare professionals using panel management: a qualitative study
Authors: Rakers Margot , van Hattem Nicoline , Simic Iris , Chavannes Niels , van Peet Petra , Bonten Tobias , Vos Rimke , van Os Hendrikus
Published: April 2024

Background

While remote patient management (RPM) has the potential to assist in achieving treatment targets for cardiovascular risk factors in primary care, its effectiveness may vary among different patient subgroups. Panel management, which involves proactive care for specific patient risk groups, could offer a promising approach to tailor RPM to these groups. This study aims to (i) assess the perception of healthcare professionals and other stakeholders regarding the adoption and (ii) identify the barriers and facilitators for successfully implementing such a panel management approach.

Methods

In total, nineteen semi-structured interviews and two focus groups were conducted in the Netherlands. Three authors reviewed the audited transcripts. The Consolidated Framework for Implementation Strategies (CFIR) domains were used for the thematic analysis.

Results

A total of 24 participants (GPs, nurses, health insurers, project managers, and IT consultants) participated. Overall, a panel management approach to RPM in primary care was considered valuable by various stakeholders. Implementation barriers encompassed concerns about missing necessary risk factors for patient stratification, additional clinical and technical tasks for nurses, and reimbursement agreements. Facilitators included tailoring consultation frequency and early detection of at-risk patients, an implementation manager accountable for supervising project procedures and establishing agreements on assessing implementation metrics, and ambassador roles.

Conclusion

Panel management could enhance proactive care and accurately identify which patients could benefit most from RPM to mitigate CVD risk. For successful implementation, we recommend having clear agreements on technical support, financial infrastructure and the criteria for measuring evaluation outcomes.
The role of clinic-based breastfeeding peer counseling on breastfeeding rates among low-income patients
Authors: Awosemusi Yetunde , Keenan-Devlin Lauren , Martinez Noelle Griffin , Yee Lynn M. , Borders Ann E. B.
Published: April 2024

Background

Despite the benefits of breastfeeding (BF), rates remain lower than public health targets, particularly among low-income Black populations. Community-based breastfeeding peer counselor (BPC) programs have been shown to increase BF. We sought to examine whether implementation of a BPC program in an obstetric clinical setting serving low-income patients was associated with improved BF initiation and exclusivity.

Methods

This is a quasi-experimental time series study of pregnant and postpartum patients receiving care before and after implementation of a BPC program in a teaching hospital affiliated prenatal clinic. The role of the BPC staff included BF classes, prenatal counseling and postnatal support, including in-hospital assistance and phone triage after discharge. Records were reviewed at each of 3 time points: immediately before the hire of the BPC staff (2008), 1-year post-implementation (2009), and 5 years post-implementation (2014). The primary outcomes were rates of breastfeeding initiation and exclusivity prior to hospital discharge, secondary outcomes included whether infants received all or mostly breastmilk during inpatient admission and by 6 weeks post-delivery. Bivariable and multivariable analyses were utilized as appropriate.

Results

Of 302 patients included, 52.3% identified as non-Hispanic Black and 99% had Medicaid-funded prenatal care. While there was no improvement in rates of BF initiation, exclusive BF during the postpartum hospitalization improved during the 3 distinct time points examined, increasing from 13.7% in 2008 to 32% in 2014 (2009 aOR 2.48, 95%CI 1.13–5.43; 2014 aOR 1.82, 95%CI 1.24–2.65). This finding was driven by improved exclusive BF for patients who identified as Black (9.4% in 2008, 22.9% in 2009, and 37.9% in 2014, p = 0.01).

Conclusion

Inpatient BF exclusivity significantly increased with the tenure of a BPC program in a low-income clinical setting. These findings demonstrate that a BPC program can be a particularly effective method to address BF disparities among low-income Black populations.
Association between body mass index and tic disorders in school-age children
Authors: Bai Lu , Wang Xia , Niu Ruijie , Zhao Mengchuan , Zhao Ziwei , Jia Pengyu , Sun Suzhen
Published: April 2024

Objective

To explore the relationship between body mass index (BMI ) and the severity of tic disorders (TDs) in children 6–14 years old.

Methods

A total of 86 children diagnosed with TDs in a hospital between Jan. 2023 and Sept. 2023 were collected by convenient sampling method, and the general data and TD-specific data were collected and analyzed.

Results

Univariate analysis showed that patients with different Yale Global Tic Severity Scale (YGTSS) grades had statistically significant differences in age, BMI, residence, snacking pattern, weekly physical exercise frequency, weekly physical exercise time, and proportion of cesarean birth. Multiple linear regression analysis showed that the YGTSS score grades were related to BMI, snacking pattern, and cesarean birth of the patients. Correlation analysis revealed a positive correlation between BMI grades and the YGTSS score grades, with a higher BMI indicating more severe TDs. Predictive value evaluation showed that BMI, snacking pattern, and cesarean birth had predictive values for TD severity, and the highest value was found in the combined prediction.

Conclusion

BMI, snacking pattern, and cesarean birth are of predictive values for the severity of TDs. In addition, BMI is positively correlated with the severity of TDs, and a higher BMI suggests more severe TDs.
Racial and ethnic disparities in access to community-based perinatal mental health programs: results from a cross-sectional survey
Authors: Rokicki Slawa , Patel Mitu , Suplee Patricia D. , D’Oria Robyn
Published: April 2024

Background

Perinatal mental health is a major public health problem that disproportionately affects people from racial and ethnic minority groups. Community-based perinatal mental health programs, such as peer support groups, are essential tools for the prevention and treatment of perinatal depression. Yet, little is known about racial and ethnic disparities in accessibility and utilization of community-based perinatal mental health programs.

Methods

We conducted a cross-sectional study using an online survey with program administrators representing perinatal mental health community-based services and support programs throughout New Jersey. Descriptive analysis and mapping software was used to analyze the data.

Results

Thirty-three program administrators completed the survey. Results showed substantial racial and ethnic disparities in availability and utilization of community-based programs. In the majority of programs, Black, Hispanic, and Asian individuals made up less than 10% of total annual participants and less than 10% of facilitators. There were also geographic disparities in program accessibility and language availability across counties. Program administrators identified mental health stigma, lack of support from family, fear of disclosure of mental health challenges, social determinants, lack of language-concordant options in programs, and limited awareness of programs in the community as significant barriers to participation of racial and ethnic minorities. Strategies to address barriers included adding language options, improving program outreach, and increasing diversity of facilitators.

Conclusions

This study provides new evidence on racial and ethnic disparities in access to community-based perinatal mental health programs. Efforts to build the resources and capacities of community-based programs to identify equity gaps, increase diversity of staff, and address barriers to participation is critical to reducing racial and ethnic inequities in perinatal mental health.
The role of colchicine in the management of COVID-19: a Meta-analysis
Authors: Elshiwy Kholoud , Amin Ghada Essam El-Din , Farres Mohamed Nazmy , Samir Rasha , Allam Mohamed Farouk
Published: April 2024

Background

The Coronavirus disease 2019 (COVID-19) pandemic has robustly affected the global healthcare and economic systems and it was caused by coronavirus-2 (SARS-CoV-2). The clinical presentation of the disease ranges from a flu-like illness to severe pneumonia and death. Till September 2022, the cumulative number of cases exceeded 600 million worldwide and deaths were more than 6 million. Colchicine is an alkaloid drug that is used in many autoinflammatory conditions e.g., gout, familial Mediterranean fever, and Behçet’s syndrome. Colchicine inhibits the production of superoxide and the release of interleukins that stimulate the inflammatory cascade. Colchicine decreases the differentiation of myofibroblast and the release of fibrotic mediators including transforming growth factor (TGF-β1) that are related to the fibrosis. Moreover, colchicine has been used to traet viral myocarditis caused by CMV or EBV, interstitial pneumonia, and pericarditis resulting from influenza B infection. Additionally, colchicine is considered safe and affordable with wide availability.

Objective

The aim of the current study was to assess the evidence of colchicine effectiveness in COVID-19 treatment.

Methods

A comprehensive review of the literature was done till May 2022 and yielded 814 articles after ranking the articles according to authors and year of publication. Only 8 clinical trials and cohort studies fulfilling the inclusion criteria were included for further steps of data collection, analysis, and reporting.

Results

This meta-analysis involved 16,488 patients; 8146 patients in the treatment group and 8342 patients in the control group. The results showed that colchicine resulted in a significant reduction in the mortality rate among patients received colchicine in comparison with placebo or standard care (RR 0.35, 95%CI: 0.15–0.79). Colchicine resulted in a significant decrease in the need for O2 therapy in patients with COVID-19 (RR 0.07, 95%CI 0.02–0.27, P = 0.000024). However, colchicine had no significant effect on the following outcomes among COVID-19 patients: the need for hospitalization, ICU admission, artificial ventilation, and hospital discharge rate. Among the PCR confirmed COVID-19 patients, colchicine decreased the hospitalization rate (RR 0.75, 95%CI 0.57–0.99, P = 0.042). However, colchicine had no effect on mortality and the need for mechanical ventilation among this subgroup.

Conclusion

Colchicine caused a significant clinical improvement among COVID-19 patients as compared with the standard care or placebo, in terms of the need for O2, and mortality. This beneficial effect could play a role in the management of COVID-19 especially severe cases to decrease need for oxygen and to decrease mortality among these patients.
Predictors of quality of life, functional status, depression and fatigue in early arthritis: comparison between clinically suspect arthralgia, unclassified arthritis and rheumatoid arthritis
Authors: Torlinska Barbara , Raza Karim , Filer Andrew , Jutley Gurpreet , Sahbudin Ilfita , Singh Ruchir , de Pablo Paola , Rankin Elizabeth , Rhodes Benjamin , Amft Nicole , Justice Elizabeth , McGrath Catherine , Baskar Sangeetha , Trickey Jeanette , Calvert Melanie , Falahee Marie
Published: April 2024

Background

Rheumatoid arthritis (RA) is often preceded by symptomatic phases during which classification criteria are not fulfilled. The health burden of these “at-risk” stages is not well described. This study assessed health-related quality of life (HRQoL), function, fatigue and depression in newly presenting patients with clinically suspect arthralgia (CSA), unclassified arthritis (UA) or RA.

Methods

Cross-sectional analysis of baseline Patient-Reported Outcome Measures (PROMs) was conducted in patients from the Birmingham Early Arthritis Cohort. HRQoL, function, depression and fatigue at presentation were assessed using EQ-5D, HAQ-DI, PHQ-9 and FACIT-F. PROMs were compared across CSA, UA and RA and with population averages from the HSE with descriptive statistics. Multivariate linear regression assessed associations between PROMs and clinical and sociodemographic variables.

Results

Of 838 patients included in the analysis, 484 had RA, 200 had CSA and 154 had UA. Patients with RA reported worse outcomes for all PROMs than those with CSA or UA. However, “mean EQ-5D utilities were 0.65 (95%CI: 0.61 to 0.69) in CSA, 0.61 (0.56 to 0.66) in UA and 0.47 (0.44 to 0.50) in RA, which was lower than in general and older (≥ 65 years) background populations.” In patients with CSA or UA, HRQoL was comparable to chronic conditions such as heart failure, severe COPD or mild angina. Higher BMI and older age (≥ 60 years) predicted worse depression (PHQ-9: -2.47 (-3.85 to -1.09), P < 0.001) and fatigue (FACIT-F: 5.05 (2.37 to 7.73), P < 0.001). Women were more likely to report worse function (HAQ-DI: 0.13 (0.03 to 0.21), P = 0.01) and fatigue (FACIT-F: -3.64 (-5.59 to -1.70), P < 0.001), and residents of more deprived areas experienced decreased function (HAQ-DI: 0.23 (0.10 to 0.36), P = 0.001), greater depression (PHQ-9: 1.89 (0.59 to 3.18), P = 0.004) and fatigue (FACIT-F: -2.60 (-5.11 to 0.09), P = 0.04). After adjustments for confounding factors, diagnostic category was not associated with PROMs, but disease activity and polypharmacy were associated with poorer performance across all PROMs.

Conclusions

Patient-reported outcomes were associated with disease activity and sociodemographic characteristics. Patients presenting with RA reported a higher health burden than those with CSA or UA, however HRQoL in the pre-RA groups was significantly lower than population averages.
Efficacy of a high-intensity home stretching device and traditional physical therapy in non-operative management of adhesive capsulitis - a prospective, randomized control trial
Authors: Teytelbaum David E. , Kumar Neil S. , Dent Craig S. , Neaville Spencer , Warren Deborah H. , Simon Peter , Baker Christopher E.
Published: April 2024

Background

Historically, in-person physical therapy serves as a foundational component of nonoperative treatment of adhesive capsulitis (AC). This study compares the effectiveness of an at-home high-intensity stretch (HIS) device to traditional physical therapy (PT) and to PT in combination with the HIS device. We hypothesize that the HIS device will be as effective as PT alone or as combination therapy in the first-line treatment of AC and use of the HIS device will exhibit improvement at higher rate.

Methods

Thirty-four patients with idiopathic adhesive capsulitis and a minimum of 12 months follow-up were included in this study. Patients were randomized into one of the three groups: HIS device, PT alone, or HIS device + PT. Passive range of motion (ROM), American Shoulder and Elbow Surgeons (ASES), and Simple Shoulder Test (SST) scores were measured. Additionally, patient satisfaction, compliance and complications were recorded. Paired t-test, ANOVA and Chi-squared tests were used in analysis.

Results

Final ROM in all planes improved for all groups compared to baseline (p < 0.001), with only HIS device group able to restore > 95% of contralateral ROM in all planes at final follow-up. Patients with PT alone were on average slowest to improve ROM from baseline, at 3 months, 6 months, and 1 year in all planes except internal rotation. ASES and SST scores improved for all groups when compared to baseline (p < 0.001). Use of HIS-device resulted in greater improvement in SST and ASES Total scores compared to PT alone (p = 0.045, and p = 0.048, respectively).

Conclusions

Use of an at-home high-intensity stretching device for conservative treatment of idiopathic adhesive capsulitis improves outcomes in ROM and in ASES and SST scores both when used as an adjunct to physical therapy and when used alone.

Trial registration

The study protocol was registered at www.clinicaltrials.gov (20/05/2022, NCT05384093).
Mendelian randomization study supports positive bidirectional causal relationships between genetically predicted insomnia symptom and liability to benign prostatic hyperplasia
Authors: Li Nannan , Yang Ke , Deng Liang , Zeng Youjie , Cao Si , Chen Dong
Published: April 2024

Background

Sleep quality may be related to benign prostatic hyperplasia (BPH), however causal associations have not been established. This study aimed to evaluate causal relationships between six sleep traits ([i] day time napping, [ii] daytime sleepiness, [iii] insomnia, [iv] long sleep duration, [v] short sleep duration, and [vi] sleep duration per hour) and BPH through a bidirectional Mendelian randomization (MR) study.

Methods

Genome-wide association summary statistics of sleep traits and BPH were downloaded from public databases. Inverse variance weighting (IVW) was used as the main approach for causal inference. For causal estimates identified by IVW, various sensitivity analyses were performed to assess the reliability of the results: (i) four additional MR methods to complement IVW; (ii) Cochran’s Q test to assess heterogeneity; (iii) MR-Egger intercept test and MR-PRESSO global test to assess horizontal pleiotropy; and (iv) leave-one-out method to assess stability.

Results

Forward MR analyses indicated that genetically predicted insomnia symptom significantly increased BPH risk (OR = 1.267, 95% CI: 1.003–1.601, P = 0.048), while reverse MR analyses identified that genetically predicted liability to BPH significantly increased the incidence of insomnia (OR = 1.026, 95% CI: 1.000-1.052, P = 0.048). In a replicate MR analysis based on summary statistics including exclusively male participants, the finding of increased risk of BPH due to genetically predicted insomnia symptom was further validated (OR = 1.488, 95% CI: 1.096–2.022, P = 0.011). No further causal links were identified. In addition, sensitivity tests demonstrated the reliability of the MR results.

Conclusion

This study identified that a higher prevalence of genetically predicted insomnia symptoms may significantly increase the risk of BPH, while genetically predicted liability to BPH may in turn increase the incidence of insomnia symptom. Therefore, improving sleep quality and reducing the risk of insomnia could be a crucial approach for the prevention of BPH.
Comparison of the different methods of width estimation in unerupted canine and premolars
Authors: Ghasemi Tania , Sabbaghzadeh Morteza , Mollaei Melika , Mirzaei Maysam
Published: April 2024

Background

There are different methods for determining the required space for unerupted teeth. However, the accuracy of these techniques varies depending on ethnic differences. Therefore, the current study was performed to compare the accuracy of four methods for estimating the mesiodistal width of unerupted canines and premolars in a population of northern Iran.

Methods

The present cross-sectional study was conducted on 50 pairs of dental casts of patients aged 12–24 years old. The mesiodistal width of the teeth was measured with a digital caliper by two observers (ICC < 0.9), and the mean value was recorded. The space required for eruption of canines and premolars was obtained by the Tanaka-Johnson formula and the Moyers tables and compared with the actual value by paired t test.

Results

The Tanaka-Johnson formula had overestimation in the maxilla and mandible, which was statistically significant (p < 0.001). The values obtained from the Moyers tables in different confidence levels were not accurate. However, the 65% level for the mandible had almost no difference from the actual value (P = 0.996 and r2 = 0.503). Furthermore, linear regression was obtained based on the total mesiodistal width of the maxillary first molar and mandibular central incisor (maxilla: Yx= 0.613X + 2.23 and mandible: Ym= 0.618X + 1.6) and the total mesiodistal width of the mandibular first molar and maxillary central incisor in each jaw (maxilla: Yx = 0.424X + 5.021 and mandible: Ym = 0.447X + 3.631).

Conclusion

The Tanaka-Johnson method was overestimated in the population of northern Iran. The 85% and 75% confidence levels of the Moyers table have the best clinical results for the maxilla and mandible, respectively. Regression based on maxillary first molars and mandibular central incisors has better results.
Pediatric upper lip myopericytoma: a case report and comprehensive review
Authors: Wei Bin , Liu Gui , Li Kun , Quan Hongzhi
Published: April 2024

Background

Myopericytoma is a rare spindle cell tumor of mesenchymal origin, typically benign, characterized by concentric proliferation of tumor cells around blood vessels within subcutaneous tissue. It primarily occurs in middle-aged adults and is often located in distal extremities, although cases have been reported in proximal extremities and head-neck regions. However, occurrences within the oral cavity are exceedingly rare. To date, literature reviews have identified only two cases in children under 10 years old and reported only five cases of myopericytoma occurring in the lip region. We provide a comprehensive review and analysis of all documented cases to better understand this condition.

Case presentation

A 7-year-old girl presented to oral and maxillofacial surgery with the discovery of a painless mass on the inner aspect of the upper lip. The diagnosis of myopericytoma was confirmed by histological examination (HE staining), alcian blue staining, and immunohistochemistry.

Conclusions

Following surgical excision, there were no signs of recurrence at a 3-month follow-up. The pathological diagnosis of myopericytoma is quite challenging, and immunohistochemical testing is necessary.
Oral mouthwashes for asymptomatic to mildly symptomatic adults with COVID-19 and salivary viral load: a randomized, placebo-controlled, open-label clinical trial
Authors: Onozuka Daisuke , Takatera Satoko , Matsuo Hiroo , Yoshida Hisao , Hamaguchi Shigeto , Yamamoto Shungo , Sada Ryuichi Minoda , Suzuki Koichiro , Konishi Keiji , Kutsuna Satoshi
Published: April 2024

Background

Recent randomized clinical trials suggest that the effect of using cetylpyridinium chloride (CPC) mouthwashes on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load in COVID-19 patients has been inconsistent. Additionally, no clinical study has investigated the effectiveness of on-demand aqueous chlorine dioxide mouthwash against COVID-19.

Methods

We performed a randomized, placebo-controlled, open-label clinical trial to assess for any effects of using mouthwash on the salivary SARS-CoV-2 viral load among asymptomatic to mildly symptomatic adult COVID-19-positive patients. Patients were randomized to receive either 20 mL of 0.05% CPC, 10 mL of 0.01% on-demand aqueous chlorine dioxide, or 20 mL of placebo mouthwash (purified water) in a 1:1:1 ratio. The primary endpoint was the cycle threshold (Ct) values employed for SARS-CoV-2 salivary viral load estimation. We used linear mixed-effects models to assess for any effect of the mouthwashes on SARS-CoV-2 salivary viral load.

Results

Of a total of 96 eligible participants enrolled from November 7, 2022, to January 19, 2023, 90 were accepted for the primary analysis. The use of 0.05% CPC mouthwash was not shown to be superior to placebo in change from baseline salivary Ct value at 30 min (difference vs. placebo, 0.640; 95% confidence interval [CI], -1.425 to 2.706; P = 0.543); 2 h (difference vs. placebo, 1.158; 95% CI, -0.797 to 3.112; P = 0.246); 4 h (difference vs. placebo, 1.283; 95% CI, -0.719 to 3.285; P = 0.209); 10 h (difference vs. placebo, 0.304; 95% CI, -1.777 to 2.385; P = 0.775); or 24 h (difference vs. placebo, 0.782; 95% CI, -1.195 to 2.759; P = 0.438). The use of 0.01% on-demand aqueous chlorine dioxide mouthwash was also not shown to be superior to placebo in change from baseline salivary Ct value at 30 min (difference vs. placebo, 0.905; 95% CI, -1.079 to 2.888; P = 0.371); 2 h (difference vs. placebo, 0.709; 95% CI, -1.275 to 2.693; P = 0.483); 4 h (difference vs. placebo, 0.220; 95% CI, -1.787 to 2.226; P = 0.830); 10 h (difference vs. placebo, 0.198; 95% CI, -1.901 to 2.296; P = 0.854); or 24 h (difference vs. placebo, 0.784; 95% CI, -1.236 to 2.804; P = 0.447).

Conclusions

In asymptomatic to mildly symptomatic adults with COVID-19, compared to placebo, the use of 0.05% CPC and 0.01% on-demand aqueous chlorine dioxide mouthwash did not lead to a significant reduction in SARS-CoV-2 salivary viral load. Future studies of the efficacy of CPC and on-demand aqueous chlorine dioxide mouthwash on the viral viability of SARS-CoV-2 should be conducted using different specimen types and in multiple populations and settings.
Prevalence of high-risk human papillomavirus infection among women with diabetes mellitus in Accra, Ghana
Authors: Atiase Yacoba , Effah Kofi , Mawusi Wormenor Comfort , Tekpor Ethel , Aku Catherine Morkli Esu , Boafo Eunice , Yorke Ernest , Aryee Robert , Essel Nana Owusu Mensah , Danyo Stephen , Kemawor Seyram , Akpalu Josephine
Published: April 2024

Background

There is increasing evidence of a higher risk and poorer prognosis of cervical cancer among women with diabetes mellitus (DM) compared to the general population. These are mediated by higher susceptibility to persistent high-risk human papillomavirus (hr-HPV) infection due to dysfunctional clearance in an immunocompromised state. We aimed to determine the prevalence of hr-HPV infection and cervical lesions in a cohort of women with DM in Ghana. We further disaggregated the prevalence according to DM type and explored factors associated with hr-HPV infection.

Methods

This retrospective descriptive cross-sectional study assessed 198 women with DM who underwent cervical screening via concurrent hr-HPV DNA testing and visual inspection with acetic acid in an outpatient department of the National Diabetes Management and Research Centre in Korle-Bu Teaching Hospital, Accra from March to May 2022. Univariate and multivariable binary logistic regression were used to explore factors associated with hr-HPV positivity.

Results

Among 198 women with DM (mean age, 60.2 ± 12.1 years), the overall hr-HPV prevalence rate was 21.7% (95% CI, 16.1–28.1), disaggregated as 1.5% (95% CI, 0.3–4.4) each for HPV16 and HPV18 and 20.7% (95% CI, 15.3–27.0) for other HPV genotype(s). Respective hr-HPV prevalence rates were 37.5% (95% CI, 15.2–64.6) for type 1 DM, 19.8% (95% CI, 13.9–26.7) for type 2 DM, and 25.0% (95% CI, 8.7–49.1) for unspecified/other DM types. Past use of the combined contraceptive pill independently increased the risk of hr-HPV infection by approximately three times (adjusted odds ratio [aOR] = 2.98; 95% CI, 1.03 − 8.64; p-value = 0.045), whereas each unit increase in FBG level increased the odds of hr-HPV infection by about 15% (aOR = 1.15; 95% CI, 1.02 − 1.30; p-value = 0.021).

Conclusion

Our study points to a high prevalence of hr-HPV among women with DM and highlights a need for glycemic control among them as this could contribute to lowering their odds of hr-HPV infection. The low overall rates of HPV vaccination and prior screening also indicate a need to build capacity and expand the scope of education and services offered to women with DM as regards cervical precancer screening.
Development and validation of the hospice professional coping scale among Chinese nurses
Authors: Zhang Yanting , Zheng Li , He Yanling , Han Min , Wang Yu , Xv Jinyu , Qiu Hui , Yang Liu
Published: April 2024

Background

Hospice care professionals often experience trauma patient deaths and multiple patient deaths in a short period of time (more so than other nurses). This repeated exposure to the death process and the death of patients leads to greater psychological pressure on hospice care professionals. But at present, people pay more attention to the feelings and care burden of the family members of dying patients but pay less attention to medical staff. Thus, this study aimed to develop a scale on the burden of care for hospice care providers and assess the coping capacity of hospice professionals. Raising awareness of the psychological burden of hospice professionals.

Methods

Through a literature review, research group discussion, Delphi method and a pre-survey of professional coping skills among nurses, 200 hospice professionals who had received training in hospice care from pilot institutions engaged in or providing hospice care were selected for investigation. Cronbach’s α coefficient and split-half reliability were used to test the internal consistency of the scale, and content validity and explore factor analysis (EFA) were used to test the construct validity of the scale.

Results

Two rounds of Delphi methods were carried out, and the effective recovery rate was 100%. The expert authority coefficients of the two rounds were 0.838 and 0.833, respectively. The Kendall’s W coefficient of experts in the first round was 0.121 ~ 0.200 (P < 0.05), and the Kendall’s W coefficient of the second round was 0.115–0.136 (P < 0.05), indicating a good level of expert coordination. The final survey scale for the care burden of hospice professionals included four dimensions—working environment (9 items), professional roles (8 items), clinical nursing (9 items) and psychological burden (7 items)—with a total of 33 items. The total Cronbach’s α coefficient of the scale was 0.963, and the Cronbach’s α coefficients of the working environment, professional roles, clinical nursing and psychological burden dimensions were 0.920, 0.889, 0.936 and 0.910, respectively. The total split-half reliability of the scale was 0.927, and the split-half reliability of each dimension was 0.846, 0.817, 0.891, and 0.832. The content validity of the scale items ranged from 0.90 to 1.00. Exploratory factor analysis revealed 5 common factors, with a total cumulative contribution rate of 68.878%. The common degree of each item in the scale was > 0.4, and the factor loading of each item was also > 0.4.

Conclusion

The scale is an open-access, short, easy-to-administer scale. And which for assessing hospice care burden among hospice professionals developed in this study demonstrated strong reliability and validity. This tool can serve as a dependable instrument for evaluating the burden of hospice care for terminally ill patients by professionals in the hospice setting.
Assessing the preparedness and future-readiness of Malaysian community pharmacists in Klang Valley regarding the use of medical marijuana
Authors: Kuang Fu Wai , Farrukh Muhammad Junaid
Published: April 2024

Background

This study investigated community pharmacists' level of knowledge and attitude towards medical marijuana and its association with sociodemographic characteristics.

Methods

A cross-sectional study was conducted from 21 February 2022 to 15 November 2022. Community pharmacists working in Klang Valley were given a self-administered questionnaire. This survey instrument facilitated the collection of information about their sociodemographic attributes, training background, and knowledge and attitude concerning medical marijuana. Through rigorous analysis of the accumulated data, discernible factors correlating with the levels of knowledge and attitudes surrounding medical marijuana were identified.

Results

The majority (n=149, 53.8%) of participants had low knowledge of medical marijuana. Participants with lower knowledge of medical marijuana tend to have a negative attitude toward medical marijuana. Besides that, male participants showed higher knowledge of medical marijuana than female participants. Furthermore, it was found that atheists had the most negative attitude among other religions toward medical marijuana.

Conclusion

Most community pharmacists in Malaysia lack sufficient knowledge about medical marijuana. This indicates that Malaysian pharmacists are not future-ready and need to equip themselves with adequate knowledge of the indications and adverse effects of medical marijuana if it is to be legalised one day. Thus, there is a need for improved training and education of pharmacists around cannabis-based medicines.
Periparturient blood T-lymphocyte PD-1 and CTLA-4 expression as potential predictors of new intramammary infections in dairy cows during early lactation (short communication)
Authors: Oliveira Ana Cláudia Dumont , de Souza Carolina Menezes Suassuna , Ramos-Sanchez Eduardo Milton , Diniz Soraia Araújo , de Souza Lima Ewerton , Blagitz Maiara Garcia , Veras Robson Cavalcante , Heinemann Marcos Bryan , Libera Alice Maria Melville Paiva Della , De Vliegher Sarne , de Carvalho Fernandes Artur Cezar , Souza Fernando Nogueira
Published: April 2024

Background

The periparturient period in dairy cows is marked by immunosuppression which increases the likelihood of infectious disorders, particularly also mastitis. An in-depth understanding of peripartum leukocyte biology is vital for the implementation of highly successful post-partum disease prevention measures. Immune checkpoint molecules, such as programmed death 1 (PD-1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4), are critical inhibitory receptors expressed on immune cells, particularly T cells, that drive immunosuppressive signaling pathways. However, the potential role of immune checkpoint molecules expression in T-cells on udder health has never been explored. Thus, the association between the occurrence of new postpartum intramammary infections (IMIs) and the expression of programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) on blood T-cells during the peripartum period was investigated.

Results

In this study, the incidence of IMIs by any pathogen in early lactation was not associated with a higher expression of PD-1 and CTLA-4 in the periparturient period. However, the incidence of IMIs by major pathogens throughout the first month of lactation was significantly associated with higher expression of PD-1 at 14 days before calving (P = 0.03) and CTLA-4 at parturition (P = 0.03) by blood T-cells. Also, the expression of CTLA-4 at D0 (P = 0.012) by T-cells was associated with the occurrence of persistent IMIs during the first month of lactation.

Conclusions

To our knowledge, this is the first report to investigate the expression of PD-1 and CTLA-4 by blood T-lymphocytes during the periparturient period in dairy cows and to explore their relationship with the incidence of new IMIs in the postpartum period. Thus, a comprehensive understanding of leukocyte biology during peripartum would appear to be a prerequisite for the identification of resilient dairy cows or targets innovative (immunological) non-antibiotic approaches in the transition period.
Milk miRNA expression in buffaloes as a potential biomarker for mastitis
Authors: Jadhav Abhishek B. , Ingole Shailesh D. , Bharucha Simin V. , Yoshitha Korsapati L. , Gaikwad Rajiv V. , Pharande Rajesh R. , Kharde Shambhudeo D.
Published: April 2024

Background

Buffaloes have the highest potential for production due to a promising gene pool that is being enhanced and upgraded. Mastitis is a significant health impediment that greatly diminishes milk yield and quality, affecting rural farmers’ livelihoods. The traditional gold standard used for diagnosing mastitis or subclinical mastitis is CMT, but it has the drawback of false positive or negative results. Subclinical mastitis, if not treated promptly, can lead to mammary tumors. To address the gap in early diagnosis of subclinical mastitis in CMT-negative milk of buffaloes, we performed a retrospective analysis and evaluated the milk miRNA expression profiles as potential biomarkers.

Results

Thirty buffalo milk samples based on clinical signs and CMT were divided into normal, subclinical, and clinical mastitis. SCC evaluation showed significant differences between the groups. The data analysis demonstrated that the elevation of miR-146a and miR-383 differed substantially between normal, subclinical, and clinical mastitis milk of buffaloes with 100% sensitivity and specificity. The relationship of SCC with miR-146a and miR-383 in normal/healthy and subclinical mastitis was positively correlated.

Conclusion

The overexpression of miR-146a and miR-383 is associated with inflammation. It can be a valuable prognostic and most sensitive biomarker for early mastitis detection in buffaloes with SCC below 2 lakhs and CMT-ve, enhancing the accuracy of subclinical mastitis diagnosis.
PySupercharge: a python algorithm for enabling ABC transporter bacterial secretion of all proteins through amino acid mutation
Authors: Kim Yerin , Kim Danny , Hieu Nguyen-Mihn , Byun Hyunjong , Ahn Jung Hoon
Published: April 2024

Background

The process of producing proteins in bacterial systems and secreting them through ATP-binding cassette (ABC) transporters is an area that has been actively researched and used due to its high protein production capacity and efficiency. However, some proteins are unable to pass through the ABC transporter after synthesis, a phenomenon we previously determined to be caused by an excessive positive charge in certain regions of their amino acid sequence. If such an excessive charge is removed, the secretion of any protein through ABC transporters becomes possible.

Results

In this study, we introduce ‘linear charge density’ as the criteria for possibility of protein secretion through ABC transporters and confirm that this criterion can be applied to various non-secretable proteins, such as SARS-CoV-2 spike proteins, botulinum toxin light chain, and human growth factors. Additionally, we develop a new algorithm, PySupercharge, that enables the secretion of proteins containing regions with high linear charge density. It selectively converts positively charged amino acids into negatively charged or neutral amino acids after linear charge density analysis to enable protein secretion through ABC transporters.

Conclusions

PySupercharge, which also minimizes functional/structural stability loss of the pre-mutation proteins through the use of sequence conservation data, is currently being operated on an accessible web server. We verified the efficacy of PySupercharge-driven protein supercharging by secreting various previously non-secretable proteins commonly used in research, and so suggest this tool for use in future research requiring effective protein production.
Scalable protein production by Komagataella phaffii enabled by ARS plasmids and carbon source-based selection
Authors: Weiss Florian , Requena-Moreno Guillermo , Pichler Carsten , Valero Francisco , Glieder Anton , Garcia-Ortega Xavier
Published: April 2024

Background

Most recombinant Komagataella phaffii (Pichia pastoris) strains for protein production are generated by genomic integration of expression cassettes. The clonal variability in gene copy numbers, integration loci and consequently product titers limit the aptitude for high throughput applications in drug discovery, enzyme engineering or most comparative analyses of genetic elements such as promoters or secretion signals. Circular episomal plasmids with an autonomously replicating sequence (ARS), an alternative which would alleviate some of these limitations, are inherently unstable in K. phaffii. Permanent selection pressure, mostly enabled by antibiotic resistance or auxotrophy markers, is crucial for plasmid maintenance and hardly scalable for production. The establishment and use of extrachromosomal ARS plasmids with key genes of the glycerol metabolism (glycerol kinase 1, GUT1, and triosephosphate isomerase 1, TPI1) as selection markers was investigated to obtain a system with high transformation rates that can be directly used for scalable production processes in lab scale bioreactors.

Results

In micro-scale deep-well plate experiments, ARS plasmids employing the Ashbya gossypii TEF1 (transcription elongation factor 1) promoter to regulate transcription of the marker gene were found to deliver high transformation efficiencies and the best performances with the reporter protein (CalB, lipase B of Candida antarctica) for both, the GUT1- and TPI1-based, marker systems. The GUT1 marker-bearing strain surpassed the reference strain with integrated expression cassette by 46% upon re-evaluation in shake flask cultures regarding CalB production, while the TPI1 system was slightly less productive compared to the control. In 5 L bioreactor methanol-free fed-batch cultivations, the episomal production system employing the GUT1 marker led to 100% increased CalB activity in the culture supernatant compared to integration construct.

Conclusions

For the first time, a scalable and methanol-independent expression system for recombinant protein production for K. phaffii using episomal expression vectors was demonstrated. Expression of the GUT1 selection marker gene of the new ARS plasmids was refined by employing the TEF1 promoter of A. gossypii. Additionally, the antibiotic-free marker toolbox for K. phaffii was expanded by the TPI1 marker system, which proved to be similarly suited for the use in episomal plasmids as well as integrative expression constructs for the purpose of recombinant protein production.