bluuebunny/crossref_metadata_2025 huggingface dataset:
Establishment and validation of serum lipid-based nomogram for predicting the risk of prostate cancer
Authors: Feng Fu , Zhong Yu-Xiang , Chen Yang , Lin Fu-Xiang , Huang Jian-Hua , Mai Yuan , Zhao Peng-Peng , Wei Wei , Zhu Hua-Cai , Xu Zhan-Ping
Published: July 2023

Background

This study aimed to explore the value of combined serum lipids with clinical symptoms to diagnose prostate cancer (PCa), and to develop and validate a Nomogram and prediction model to better select patients at risk of PCa for prostate biopsy.

Methods

Retrospective analysis of 548 patients who underwent prostate biopsies as a result of high serum prostate-specific antigen (PSA) levels or irregular digital rectal examinations (DRE) was conducted. The enrolled patients were randomly assigned to the training groups (n = 384, 70%) and validation groups (n = 164, 30%). To identify independent variables for PCa, serum lipids (TC, TG, HDL, LDL, apoA-1, and apoB) were taken into account in the multivariable logistic regression analyses of the training group, and established predictive models. After that, we evaluated prediction models with clinical markers using decision curves and the area under the curve (AUC). Based on training group data, a Nomogram was developed to predict PCa.

Results

210 (54.70%) of the patients in the training group were diagnosed with PCa. Multivariate regression analysis showed that total PSA, f/tPSA, PSA density (PSAD), TG, LDL, DRE, and TRUS were independent risk predictors of PCa. A prediction model utilizing a Nomogram was constructed with a cut-off value of 0.502. The training and validation groups achieved area under the curve (AUC) values of 0.846 and 0.814 respectively. According to the decision curve analysis (DCA), the prediction model yielded optimal overall net benefits in both the training and validation groups, which is better than the optimal net benefit of PSA alone. After comparing our developed prediction model with two domestic models and PCPT-RC, we found that our prediction model exhibited significantly superior predictive performance. Furthermore, in comparison with clinical indicators, our Nomogram’s ability to predict prostate cancer showed good estimation, suggesting its potential as a reliable tool for prognostication.

Conclusions

The prediction model and Nomogram, which utilize both blood lipid levels and clinical signs, demonstrated improved accuracy in predicting the risk of prostate cancer, and consequently can guide the selection of appropriate diagnostic strategies for each patient in a more personalized manner.
Improving the regeneration rate of deep lethal mutant protoplasts by fusion to promote efficient L-lysine fermentation
Authors: Li Nan , Lu Jie , Wang Zirui , Du Peng , Li Piwu , Su Jing , Xiao Jing , Wang Min , Wang Junqing , Wang Ruiming
Published: July 2023

Background

L-lysine is widely used for feed and special diet products. The transformation of fermentation strains plays a decisive role in the development of these industries. Based on the mutation breeding theory and metabolic engineering methods, this study aimed to improve the regeneration rate of high-lethality protoplasts by combining multiple mutagenesis and homologous cell fusion techniques to efficiently concentrate multiple dominant mutations and optimize the L-lysine production strain Escherichia coli QDW.

Results

In order to obtain the best protoplasts, the optimal enzymolysis time was selected as 4 h. The optimal lysozyme concentration was estimated at 0.8 mg/mL, because the protoplast formation rate and regeneration rate reached 90% and 30%, respectively, and their product reached the maximum. In this study, it was necessary that UV mutagenesis be excessive to obtain an expanded mutation library. For high lethality protoplasts, under the premise of minimal influence on its recovery, the optimal time for UV mutagenesis of protoplasts was 7 min, and the optimal time for thermal inactivation of protoplasts at 85 ℃ was 30 min. After homologous fusion, four fusion strains of E. coli were obtained, and their stability was analyzed by flow cytometry. The L-lysine yield of QDW-UH3 increased by 7.2% compared with that of QDW in a fermentation experiment, which promoted the expression of key enzymes in L-lysine synthesis, indicating that the combination of ultraviolet mutagenic breeding and protoplast fusion technology improved the acid-production level of the fusion strain.

Conclusion

This method provides a novel approach for the targeted construction of microbial cell factories.
Vitamin D deficiency increases with age and adiposity in Emirati children and adolescents irrespective of type 1 diabetes mellitus: a case control study
Authors: Majeed Maria , Siddiqui Mohsin , Lessan Nader
Published: July 2023

Background

Association of vitamin D (25(OH)D) deficiency with obesity and diabetes has been well-established in paediatric and adult populations. This study aims to report the association of 25(OH)D deficiency with body composition and prevalence of 25(OH)D deficiency in Emirati children and adolescents, who attended a diabetes centre in the United Arab Emirates.

Methods

Using Abu Dhabi Diabetes and Obesity Study cohort, type 1 diabetes (T1D) and normoglycaemic (NG) participants between 4–19 years of age were selected. WHO criteria were used to define 25(OH)D cut-offs: deficient (< 30 nmol/L), insufficient (30-50 nmol/L) and sufficient (> 50 nmol/L). Based on CDC recommendations, BMI percentile was categorised as underweight, normal weight, overweight and obesity.

Results

After age and sex matching, 148 T1D cases and 296 NG controls were identified. 25(OH)D deficiency was observed in 22.3% (n = 33) T1D and 40.5% (n = 120) NG participants. 25(OH)D levels were lower in adolescents (15 – 19 years) than children (4 – 7 years) in both T1D and NG groups (p = 0.018 vs p < 0.001). Females were more likely to be 25(OH)D deficient in both groups. Children and adolescents with BMI ≥ 95th percentile were more likely to be 25(OH)D deficient than those with normal weight (OR: 2.69; 95% CI: 1.56, 4.64). Adiposity measures and 25(OH)D levels correlated negatively in both groups (T1D p < 0.01, NG p < 0.001).

Conclusion

Vitamin D 25(OH)D deficiency is notably prevalent in Emirati children and adolescents despite adequate sunlight throughout the year. The prevalence was lower in those with T1D which may be indicative of treatment compliance in this population. This study also confirms important negative association of serum 25(OH)D levels with body mass and obesity in this population.
Prognostic model based on telomere-related genes predicts the risk of oral squamous cell carcinoma
Authors: Yue Kun , Yao Xue
Published: July 2023

Background

This study investigated a potential prognostic model based on telomere-related genes (TRGs) for the clinical prediction of oral squamous cell carcinoma (OSCC).

Methods

Gene expression data and associated clinical phenotypes were obtained from online databases. Differentially expressed (DE)-TRGs were identified between OSCC and normal samples, followed by protein-protein interaction and enrichment analyses. Subsequently, the prognostic genes explored based on the DE-TRGs and survival data were applied in the establishment of the current prognostic model, and an integrated analysis was performed between high- and low-risk groups using a prognostic model. The expression of certain prognostic genes identified in the present study was validated using qPCR analysis and/or western blot in OSCC cell lines and clinical samples.

Results

169 DE-TRGs were identified between the OSCC samples and controls. DE-TRGs are mainly involved in functions such as hypoxia response and pathways such as the cell cycle. Eight TRGs (CCNB1, PDK4, PLOD2, RACGAP1, MET, PLK1, KPNA2, and CCNA2) associated with OSCC survival and prognosis were used to construct a prognostic model. qPCR analysis and western blot showed that most of the eight prognostic genes were consistent with the current bioinformatics results. Analysis of the high- and low-risk groups for OSCC determined by the prognostic model showed that the current prognostic model was reliable.

Conclusions

A novel prognostic model for OSCC was constructed by TRGs. PLOD2 and APLK1 may participate in the progression of OSCC via responses to hypoxia and cell cycle pathways, respectively. TRGs, including KPNA2 and CCNA2, may serve as novel prognostic biomarkers for OSCC.
The efficacy of concentrated growth factor and platelet-rich fibrin as scaffolds in regenerative endodontic treatment applied to immature permanent teeth: a retrospective study
Authors: Li Jiahua , Zheng Leilei , Daraqel Baraa , Liu Jing , Hu Yun
Published: July 2023

Background

The aim of this retrospective study was to compare the efficacy of concentrated growth factor (CGF) and platelet-rich fibrin (PRF) as scaffolds in regenerative endodontic therapy (RET).

Methods

Necrotic immature permanent teeth treated with regenerative endodontic therapy during January 2018 to August 2022 were divided into the CGF and PRF groups according to the scaffold. The CGF and PRF groups included 7 and 6 teeth, respectively. The efficacy of regenerative endodontic therapy was analyzed based on the clinical and radiological outcomes at three different follow up periods: T1 (3–6 months), T2 (6–12 months) and T3 (12–24 months). Statistical analysis was performed using the independent T test, Mann-Whitney test and Fisher’s exact test at a significance level of 0.05.

Results

The success rate of each stage in both groups was 100%. Through quantitative comparison of radiographic outcomes, there was no statistically significant difference between the two groups in terms of root development and periapical lesion healing at each stage, except that the increase rate of radiographic root area in PRF group in the T3 stage was above one in CGF group with statistically significance.

Conclusions

Both CGF and PRF had a similar clinical performance regarding resolution of clinical signs and symptoms, periapical lesion healing, and continued root development as scaffolds in RET. Further prospective studies with large samples for longer follow-up periods are needed.
“It’s a proactive intervention instead of a reactive one”: measuring facilitators and barriers regarding readiness to implement a treatment program for infants with neonatal opioid withdrawal syndrome
Authors: Holcomb Leah , Koob Caitlin , Mayo Rachel , Charron Elizabeth , Dickes Lori , Sherrill Windsor , Hudson Jennifer
Published: July 2023

Background

Managing Abstinence in Newborns (MAiN) is an evidence-based, cost-saving approach to caring for infants at risk of developing neonatal opioid withdrawal syndrome (NOWS). MAiN provides medication management in combination with education and is being implemented in hospitals across South Carolina (SC). This expansion of MAiN throughout the state includes educational training for providers on managing NOWS symptomology and evaluation support for data collection and analysis. This evaluation assessed the readiness of hospitals to implement MAiN by identifying potential barriers and facilitators to early program adoption.

Methods

We used the Consolidated Framework for Implementation Framework (CFIR) to guide the evaluation. As part of the ongoing evaluation of MAiN implementation, brief, structured interviews were conducted with healthcare providers (n = 82) at seven hospitals between 2019 and 2022 to learn more about perceived barriers and facilitators to implementation readiness. Two coders independently reviewed all transcripts and used deductive thematic analysis to code qualitative data using Atlas.ti Web using the established CFIR codebook.

Results

We identified barriers and facilitators to implementing MAiN in all five CFIR domains. Providers identified MAiN as an evidence-based, patient-centered model with the flexibility to adapt to patients’ complex needs. Specific champions, external support, alignment with providers’ personal motivation, and an adaptable implementation climate were identified as facilitators for implementation readiness. Barriers included a lack of consistent communication among hospital providers, minimal community resources to support patients and families after discharge, and a lack of provider buy-in early in implementation.

Conclusions

Key barriers and facilitators of MAiN implementation readiness were identified at seven participating hospitals throughout SC. Communication, staff and hospital culture and climate, and internal and external resource were all reported as essential to implementation. These findings could inform the MAiN program expansion in hospitals across SC.
Reduced Vrk2 expression is associated with higher risk of depression in humans and mediates depressive-like behaviors in mice
Authors: Yin Mei-Yu , Guo Lei , Zhao Li-Juan , Zhang Chen , Liu Wei-Peng , Zhang Chu-Yi , Huo Jin-Hua , Wang Lu , Li Shi-Wu , Zheng Chang-Bo , Xiao Xiao , Li Ming , Wang Chuang , Chang Hong
Published: July 2023

Background

Genome-wide association studies (GWAS) have reported single-nucleotide polymorphisms (SNPs) in the VRK serine/threonine kinase 2 gene (VRK2) showing genome-wide significant associations with major depression, but the regulation effect of the risk SNPs onVRK2as well as their roles in the illness are yet to be elucidated.

Methods

Based on the summary statistics of major depression GWAS, we conducted population genetic analyses, epigenome bioinformatics analyses, dual luciferase reporter assays, and expression quantitative trait loci (eQTL) analyses to identify the functional SNPs regulatingVRK2; we also carried out behavioral assessments, dendritic spine morphological analyses, and phosphorylated 4D-label-free quantitative proteomics analyses in mice withVrk2repression.

Results

We identified a SNP rs2678907 located in the 5’ upstream ofVRK2gene exhibiting large spatial overlap with enhancer regulatory marks in human neural cells and brain tissues. Using luciferase reporter gene assays and eQTL analyses, the depression risk allele of rs2678907 decreased enhancer activities and predicted lowerVRK2mRNA expression, which is consistent with the observations of reducedVRK2level in the patients with major depression compared with controls. Notably,Vrk2−/−mice exhibited depressive-like behaviors compared toVrk2+/+mice and specifically repressingVrk2in the ventral hippocampus using adeno-associated virus (AAV) lead to consistent and even stronger depressive-like behaviors in mice. Compared withVrk2+/+mice, the density of mushroom and thin spines in the ventral hippocampus was significantly altered inVrk2−/−mice, which is in line with the phosphoproteomic analyses showing dysregulated synapse-associated proteins and pathways inVrk2−/−mice.

Conclusions

Vrk2deficiency mice showed behavioral abnormalities that mimic human depressive phenotypes, which may serve as a useful murine model for studying the pathophysiology of depression.
Individualized dynamic methylation-based analysis of cell-free DNA in postoperative monitoring of lung cancer
Authors: Chen Kezhong , Kang Guannan , Zhang Zhihong , Lizaso Analyn , Beck Stephan , Lyskjær Iben , Chervova Olga , Li Bingsi , Shen Haifeng , Wang Chenyang , Li Bing , Zhao Heng , Li Xi , Yang Fan , Kanu Nnennaya , Wang Jun
Published: July 2023

Background

The feasibility of DNA methylation-based assays in detecting minimal residual disease (MRD) and postoperative monitoring remains unestablished. We aim to investigate the dynamic characteristics of cancer-related methylation signals and the feasibility of methylation-based MRD detection in surgical lung cancer patients.

Methods

Matched tumor, tumor-adjacent tissues, and longitudinal blood samples from a cohort (MEDAL) were analyzed by ultra-deep targeted sequencing and bisulfite sequencing. A tumor-informed methylation-based MRD (timMRD) was employed to evaluate the methylation status of each blood sample. Survival analysis was performed in the MEDAL cohort (n = 195) and validated in an independent cohort (DYNAMIC, n = 36).

Results

Tumor-informed methylation status enabled an accurate recurrence risk assessment better than the tumor-naïve methylation approach. Baseline timMRD-scores were positively correlated with tumor burden, invasiveness, and the existence and abundance of somatic mutations. Patients with higher timMRD-scores at postoperative time-points demonstrated significantly shorter disease-free survival in the MEDAL cohort (HR: 3.08, 95% CI: 1.48–6.42; P = 0.002) and the independent DYNAMIC cohort (HR: 2.80, 95% CI: 0.96–8.20; P = 0.041). Multivariable regression analysis identified postoperative timMRD-score as an independent prognostic factor for lung cancer. Compared to tumor-informed somatic mutation status, timMRD-scores yielded better performance in identifying the relapsed patients during postoperative follow-up, including subgroups with lower tumor burden like stage I, and was more accurate among relapsed patients with baseline ctDNA-negative status. Comparing to the average lead time of ctDNA mutation, timMRD-score yielded a negative predictive value of 97.2% at 120 days prior to relapse.

Conclusions

The dynamic methylation-based analysis of peripheral blood provides a promising strategy for postoperative cancer surveillance.

Trial registration

This study (MEDAL, MEthylation based Dynamic Analysis for Lung cancer) was registered on ClinicalTrials.gov on 08/05/2018 (NCT03634826). https://clinicaltrials.gov/ct2/show/NCT03634826.
Epidemiology of the first-ever cardiovascular event in people with type 1 diabetes: a retrospective cohort population-based study in Catalonia
Authors: Giménez-Pérez Gabriel , Viñals Clara , Mata-Cases Manel , Vlacho Bogdan , Real Jordi , Franch-Nadal Josep , Ortega Emilio , Mauricio Dídac
Published: July 2023

Background

Knowledge of the characteristics of first-ever cardiovascular events in type 1 diabetes may impact primary prevention strategies. This study describes the first-ever manifestation of cardiovascular disease (CVD) in patients with type 1 diabetes (T1D) in Catalonia (Spain) and evaluates differences according to age and sex.

Methods

Retrospective cohort study of patients with T1D > 30 years without CVD before 2010 registered in the SIDIAP database. The occurrence of a first cardiovascular event up to the end of 2016, the type of CV event and associations with baseline characteristics were analysed.

Results

Of 8412 patients, 884 suffered a first CV event (incidence rate 1.62 per 100 persons-years). Overall, peripheral vascular disease (39.5%) was the most frequent event. We observed a higher proportion of heart failure in women (21.7%) than in men (10.1%). In women, heart failure was the most frequent event in those > 65 years (40.5%). Decreased glomerular filtration rate (hazard ratio [HR] 5.42 [95% CI 4.32;6.80]), elevated albumin/creatinine ratio (HR 3.39 [95% CI [2.47;4.66], microvascular complications (HR 3.27 [95% CI 2.85;3.75]), and hypertension (HR 3.21 [95% CI [2.80;3.67]) were most strongly associated with a first CV event. HbA1c > 7.0% was associated with incident CVD only in patients aged < 55/60 years.

Conclusions

Peripheral artery disease in the whole cohort, and heart failure in elder subjects are the most frequent first-ever CVD events in T1D in our region. These findings deserve to be taken into account when considering primary prevention measures and when estimating CV risk in people with T1D.
From frozen cell bank to product assay: high-throughput strain characterisation for autonomous Design-Build-Test-Learn cycles
Authors: Helleckes Laura M. , Puchta Debora , Czech Hannah , Morschett Holger , Geinitz Bertram , Wiechert Wolfgang , Oldiges Marco
Published: July 2023

Background

Modern genome editing enables rapid construction of genetic variants, which are further developed in Design-Build-Test-Learn cycles. To operate such cycles in high throughput, fully automated screening, including cultivation and analytics, is crucial in the Test phase. Here, we present the required steps to meet these demands, resulting in an automated microbioreactor platform that facilitates autonomous phenotyping from cryo culture to product assay.

Results

First, an automated deep freezer was integrated into the robotic platform to provide working cell banks at all times. A mobile cart allows flexible docking of the freezer to multiple platforms. Next, precultures were integrated within the microtiter plate for cultivation, resulting in highly reproducible main cultures as demonstrated for Corynebacterium glutamicum. To avoid manual exchange of microtiter plates after cultivation, two clean-in-place strategies were established and validated, resulting in restored sterile conditions within two hours. Combined with the previous steps, these changes enable a flexible start of experiments and greatly increase the walk-away time.

Conclusions

Overall, this work demonstrates the capability of our microbioreactor platform to perform autonomous, consecutive cultivation and phenotyping experiments. As highlighted in a case study of cutinase-secreting strains of C. glutamicum, the new procedure allows for flexible experimentation without human interaction while maintaining high reproducibility in early-stage screening processes.
Health insurance coverage among women of reproductive age in rural Ghana: policy and equity implications
Authors: Ayanore Martin , Afaya Agani , Kumbeni Maxwell Tii , Laari Timothy Tienbia , Ahinkorah Bright Opoku , Salia Solomon Mohammed , Bam Victoria , Yakong Vida Nyagre , Afaya Richard Adongo , Alhassan Robert Kaba , Seidu Abdul-Aziz
Published: July 2023

Background

Globally, health insurance has been identified as a key component of healthcare financing. The implementation of health insurance policies in low and middle-income countries has led to a significant increase in access to healthcare services in these countries. This study assessed health insurance coverage and its associated factors among women of reproductive age living in rural Ghana.

Methods

This study used a nationally representative data from the 2017/2018 Ghana Multiple Indicator Cluster Survey (GMICS) and included 7340 rural women aged 15–49 years. Bivariate and multivariable logistic regression models were developed to assess the association between the explanatory and the outcome variable. Statistical significance was considered at p = 0.05.

Results

The overall prevalence of health insurance coverage among rural women in Ghana was 51.9%. Women with secondary (aOR = 1.72, 95% CI: 1.38–2.14) and higher education (aOR = 4.57, 95% CI: 2.66–7.84) were more likely to have health insurance coverage than those who had no formal education. Women who frequently listened to radio (aOR = 1.146, 95% CI: 1.01–1.30) were more likely to have health insurance coverage than those who did not. Women who had a child (aOR = 1.81, 95% CI: 1.50–2.17), two children (aOR = 1.59, 95% CI: 1.27–1.98), three children (aOR = 1.41, 95% CI: 1.10–1.80), and five children (aOR = 1.36, 95% CI: 1.03–1.79) were more likely to have health insurance coverage than those who had not given birth. Women who were pregnant (aOR = 3.52, 95% CI: 2.83–4.38) at the time of the survey, and women within the richest households (aOR = 3.89, 95% CI: 2.97–5.10) were more likely to have health insurance coverage compared to their other counterparts. Women in the Volta region (aOR = 1.36, 95% CI: 1.02–1.81), Brong Ahafo region (aOR = 2.82, 95% CI: 2.20–3.60), Northern region (aOR = 1.32, 95% CI: 1.02–1.70), Upper East region (aOR = 2.13, 95% CI: 1.63–2.80) and Upper West region (aOR = 1.56, 95% CI: 1.20–2.03) were more likely to have health insurance coverage than those in the Western region.

Conclusion

Although more than half of women were covered by health insurance, a significant percentage of them were uninsured, highlighting the need for prompt policy actions to improve coverage levels for insurance. It was found that educational level, listening to radio, parity, pregnancy status, wealth quintile, and region of residence were factors associated with health insurance coverage. We recommend better targeting and prioritization of vulnerability in rural areas and initiate policies that improve literacy and community participation for insurance programs. Further studies to establish health policy measures and context specific barriers using experimental designs for health insurance enrolments are required.
Integrated knowledge translation guidelines for trainees in health research: an environmental scan
Authors: Gallant Sarah Madeline , Cassidy Christine , Al-Rassi Joyce , Moody Elaine , Shin Hwayeon Danielle , Best Shauna , Steenbeek Audrey
Published: July 2023

Background

Collaborative health research, such as integrated knowledge translation (IKT), requires researchers to have specific knowledge and skills in working in partnership with knowledge users. Graduate students are often not provided with the opportunity to learn skills in how to establish collaborative relationships with knowledge users in the health system or communities, despite its importance in research. The objective of this environmental scan is to identify available guidelines for graduate trainees to use an IKT approach in their research.

Methods

We conducted an environmental scan with three separate systematic searches to identify guidelines available to support graduate students in engaging in an IKT approach to research: (i) a customized Google search; (ii) a targeted Canadian university website search; and (iii) emails to administrators of graduate studies programmes asking for available guidelines and documents designed for graduate students. Data were extracted using a standardized data extraction tool and analysed using a directed content analysis approach. Due to the minimal results included based on the a priori eligibility criteria, we returned to the excluded records to further review the current state of the environment on trainee support for IKT research.

Results

Our search strategy yielded 22 900 items, and after a two-step screening process with strict inclusion criteria three documents met the eligibility criteria. All three documents highlighted the need for an IKT plan for knowledge user involvement throughout the research process. Furthermore, documents emphasized the need for tangible steps to guide graduate students to engage in effective communication with knowledge users. Due to the lack of documents retrieved, we conducted a post hoc content analysis of relevant IKT documents excluded and identified five themes demonstrating increased education and engagement in an IKT approach at an interpersonal and organizational level.

Conclusion

We identified three documents providing guidance to trainees using a collaborative approach in their health research. This scan highlighted two key findings including the importance of supporting trainees to engage knowledge users in research and preparing an IKT plan alongside a research plan. Further research is needed to co-design guidelines to support graduate students and trainees in engaging in an IKT approach.
Comparison of two different intravitreal treatment regimens combined with systemic antiviral therapy for cytomegalovirus retinitis in patients with AIDS
Authors: Liang Xuemei , An Hongmei , He Huawei , Shen Baiyun , Ou Zuguo , Li Li
Published: July 2023

Purpose

To compare the efficacy and injection frequency of intravitreal low-dose vs. intermediate-dose ganciclovir therapy in acquired immune deficiency syndrome (AIDS) patients exhibiting cytomegalovirus retinitis (CMVR).

Methods

A prospective, single-centre, double-blinded, randomized controlled interventional study was conducted. Fifty patients with a total of 67 included eyes were randomly divided into low-dose (0.4 mg ganciclovir per week) and intermediate-dose (1.0 mg ganciclovir per week) groups. The primary clinical outcomes were the changes in best corrected visual acuity (BCVA) from baseline to the end of treatment and the 12-month follow-up visit as well as the number of intravitreal injections.

Results

In both groups, the median BCVA, expressed as the logarithm of the minimum angle of resolution (logMAR), improved significantly from baseline to the end of treatment (both p < 0.001), while vision loss from CMVR continued to occur at the 12-month visit. The mean number of injections was 5.8 in the low-dose group and 5.4 in the intermediate-dose group. No significant differences were detected between the two groups (p > 0.05). Regarding the location of CMVR, we found that Zone I lesions led to a worse visual outcome, more injections and a higher occurrence rate of complications than lesions in other zones (p < 0.05).

Conclusions

The efficacy and frequency of injections to treat CMVR in AIDS patients were not significantly different between low and intermediate doses. Zone I lesions were associated with a worse visual outcome, more injections and a higher occurrence rate of CMVR-related complications than lesions in other zones.
What are the determinants of antiretroviral therapy adherence among stable people living with HIV? A cross-sectional study in Cambodia
Authors: Tuot Sovannary , Sim Jian Wei , Nagashima-Hayashi Michiko , Chhoun Pheak , Teo Alvin Kuo Jing , Prem Kiesha , Yi Siyan
Published: July 2023

Background

Understanding context-specific determinants of antiretroviral therapy (ART) adherence is crucial for developing tailored interventions for improving health outcomes and achieving the UNAIDS’ third 95% target. This cross-sectional study explores factors associated with ART adherence among stable people living with HIV on ART in Cambodia.

Methods

We used baseline survey data from a quasi-experimental study conducted in 2021. The participants were recruited from 20 ART clinics in nine provinces for face-to-face interviews. A structured questionnaire collected information on sociodemographic characteristics, ART adherence, perceived ART self-efficacy, mental health, quality of life, stigma, and discrimination. We conducted bivariate and multiple logistic regression analyses to identify factors associated with ART adherence.

Results

Out of the 4101 participants, 86.5% reported adhering to ART in the past two months. The adjusted odds of ART adherence were significantly higher among participants in older age groups than those aged 15–29, participants with elevated cholesterol than those without it, participants who exhibited strong self-efficacy in health responsibility to maintain life than those with poor self-efficacy in health responsibility, participants who scored < 3 on the stigma and discrimination scale than those who scored ≥ 3, participants who scored ≥ 42 on the mental component of the quality-of-life scale than those who scored < 42. The adjusted odds of ART adherence were significantly lower in participants who earned > 301 USD per month than those who earned ≤ 100 USD per month.

Conclusion

The ART adherence rate among stable people living with HIV in this study was comparable to that of the general people living with HIV in Cambodia. The results suggest the need for innovative interventions to further reduce stigma and discrimination and strategies to improve the self-efficacy and mental health of people living with HIV to improve ART adherence.
Delineation of the phenotypes and genotypes of facial infiltrating lipomatosis associated with PIK3CA mutations
Authors: Chen Hongrui , Sun Bin , Gao Wei , Qiu Yajing , Hua Chen , Lin Xiaoxi
Published: July 2023

Background

Facial infiltrating lipomatosis (FIL) is a rare congenital disorder characterized by unilateral facial swelling, for which surgery is the prevailing therapeutic option. Several studies have shown that the development of FIL is closely associated with PIK3CA mutations. This study aimed to further identify rare clinical features and underlying molecular variants in patients with FIL.

Results

Eighteen patients were included in this study, and all patients presented with infiltrating adipose tissues confirmed by magnetic resonance imaging. Macrodactyly, polydactyly, hemimegalencephaly and hemihyperplasia were also observed in patients with FIL. In total, eight different PIK3CA mutations were detected in tissues obtained from sixteen patients, including the missense mutations p.His1047Arg (n = 4), p.Cys420Arg (n = 2), p.Glu453Lys (n = 2), p.Glu542Lys (n = 2), p.Glu418Lys (n = 1), p.Glu545Lys (n = 1), and p.His1047Tyr (n = 1) and the deletion mutation p.Glu110del (n = 3). Furthermore, the GNAQ mutation p.Arg183Gln was detected in the epidermal nevus tissue of one patient. Imaging revealed that several patients carrying hotspot mutations had more severe adipose infiltration and skeletal deformities.

Conclusions

The abundant clinical presentations and genetic profiles of FIL make it difficult to treat. PIK3CA mutations drive the pathogenesis of FIL, and PIK3CA hotspot mutations may lead to more extensive infiltration of lipomatosis. Understanding the molecular variant profile of FIL will facilitate the application of novel PI3K-targeted inhibitors.
Two cases of placental trisomy 21 mosaicism causing false-negative NIPT results
Authors: Zhao Qinfei , Chen Jing , Ren Ling , Zhang Huijuan , Liu Dedong , Xi Xuxiang , Wu Xiangsheng , Fang Chunyun , Ye Ping , Zeng Shaoying , Zhong Tianyu
Published: July 2023

Background

Non-invasive prenatal testing (NIPT) using cell-free DNA has been widely used for prenatal screening to detect the common fetal aneuploidies (such as trisomy 21, 18, and 13). NIPT has been shown to be highly sensitive and specific in previous studies, but false positives (FPs) and false negatives (FNs) occur. Although the prevalence of FN NIPT results for Down syndrome is rare, the impact on families and society is significant.

Case presentation

This article described two cases of foetuses that tested “negative” for trisomy 21 by NIPT technology using the semiconductor sequencing platform. However, the fetal karyotypes of amniotic fluid were 46,XY, + 21 der(21;21)(q10;q10) and 47,XY, + 21 karyotypes, respectively. Placental biopsies confirmed that, in the first case, the chromosome 21 placenta chimerism ratio ranged from 13 to 88% with the 46,XX, + 21,der(21;21)(q10;q10)[86]/46,XX[14] karyotype of placental chorionic cells (middle of fetal-side placental tissue). However, in the second case, of all the placental biopsies, percentage of total chimerism was less than 30%; and placental biopsies taken at the middle of maternal side and middle of fetal side, also had variable trisomy 2 mosaicism levels of 10% and 8%, respectively. Ultimately, the pregnancies were interrupted at 30 gestational age (GA) and 27GA, respectively.

Conclusions

In this study, we present two cases of FN NIPT results that might have been caused by biological mechanisms, as opposed to poor quality, technical errors, or negligence. Clinical geneticists and their patients must understand that NIPT is a screening procedure.
GeneXpert MTB/RIF Ultra performance to detect uncommon rpoB mutations in Mycobacterium tuberculosis
Authors: Rigouts Leen , Keysers Jelle , Rabab Reenaers , Fissette Kristina , van Deun Armand , de Jong Bouke Catherine
Published: July 2023

Objective

To investigate the performance of GeneXpert MTB/RIF Ultra to accurately detect rifampicin resistance for less common rpoB mutations that potentially confer phenotypic resistance, we tested 28 such Mycobacterium tuberculosis cultures with Xpert Ultra.

Results

They represented 22 different (combinations of) rpoB mutations. Of 28 isolates tested, one was reported by Xpert Ultra as “No rifampicin resistance detected”, 8 yielded a “Rifampicin indeterminate” result, and 19 were identified as rifampicin resistant. Overall, our results corroborate previous observations on the “Indeterminate” results for mutations at codon 432, while we add Lys446Gln as additional “Indeterminate” result and Pro439Leu as a false rifampicin-susceptible result. Furthermore, we document other uncommon point mutations and indels across the rpoB gene that are mostly correctly identified as rifampicin resistant by Xpert ultra (V3). Taken together, “Indeterminate” results in Xpert Ultra may indicate underlying rpoB mutations within the rifampicin-resistance determining region and thus increase the post-test probability of rifampicin resistance, albeit to an unknown extent.
Inactivation of poly(3-hydroxybutyrate) (PHB) biosynthesis in ‘Knallgas’ bacterium Xanthobacter sp. SoF1
Authors: Jämsä Tytti , Tervasmäki Petri , Pitkänen Juha-Pekka , Salusjärvi Laura
Published: July 2023

Aerobic hydrogen-oxidizing ‘Knallgas’ bacteria are promising candidates for microbial cell factories due to their ability to use hydrogen and carbon dioxide as the sole energy and carbon sources, respectively. These bacteria can convert atmospheric CO2 to chemicals which could help to mitigate climate change by replacing fossil fuel-based chemicals. A known method to enhance the product yield is to disrupt competing metabolic pathways in the host organism. One such pathway in many ‘Knallgas’ bacteria is polyhydroxybutyrate (PHB) biosynthesis. In this study, the PHB biosynthesis genes of a non-model ‘Knallgas’ bacterium Xanthobacter sp. SoF1 were identified. Consequently, the phaA, phaB and phaC genes were individually deleted and the resulting knockouts were evaluated for their ability to produce PHB in autotrophic shake flask and small-scale bioreactor cultivations. The results demonstrate that PHB production was inactivated in the phaC1 knockout strain, which advances the development of Xanthobacter sp. SoF1 as a production host.

Graphical Abstract
Impact of iron supplementation on patient outcomes for women with abnormal uterine bleeding: a protocol for a systematic review and meta-analysis
Authors: Nazaryan Hasmik , Watson Megan , Ellingham Dana , Thakar Swarni , Wang Andrea , Pai Menaka , Liu Yang , Rochwerg Bram , Gabarin Nadia , Arnold Donald , Sirotich Emily , Zeller Michelle P.
Published: July 2023

Background

Abnormal uterine bleeding (AUB), which includes heavy menstrual bleeding (HMB), is a common condition placing women at increased risk for developing iron deficiency and iron deficiency anemia (IDA). Depletion of iron stores has negative implications on physical, social, and emotional health, as well as quality of life. Iron supplements are safe, effective, and readily available, while red blood cell (RBC) transfusions have inherent risks including infectious and immune reactions. Despite high prevalence of IDA among women with AUB, there are limited studies on the impact of iron therapies on patient outcomes. This systematic review and meta-analysis will evaluate the impact of iron supplementation on patient outcomes for women with AUB, when compared to combination therapy, no intervention, placebo, or standard of care.

Methods

We will conduct a systematic review and meta-analysis of randomized controlled trials and observational studies evaluating the impact of iron interventions on patient outcomes for women with AUB. Systematic literature searches will be conducted in major databases including MEDLINE, EMBASE, CENTRAL, CINAHL, and Web of Science. Studies assessing the impact of iron interventions on patient outcomes in women experiencing AUB, in comparison to combination therapy, no intervention, placebo, or standard of care, will be included in the review. Independent reviewers will screen for eligibility, assess risk of bias, and abstract data. Overall certainty of evidence for each outcome will be assessed using the GRADE approach. We will meta-analyze outcomes which are sufficiently homogeneous to summarize intervention effects and narratively synthesize nonhomogeneous outcomes. The main outcomes of interest are hemoglobin levels immediately prior to surgery and post-operatively, number of RBC transfusions, and adverse effects. Secondary outcomes will include length of hospital stay, intraoperative blood loss, adverse and side effects, quality of life, and iron indices.

Discussion

This review will evaluate the impact of iron interventions on patient outcomes in women with IDA secondary to AUB with focus on changes in hematological and iron indices, red blood cell utilization, quality of life, cost of treatment, and adverse events. The results will inform evidence-based clinical practice for the management of iron deficiency and IDA secondary to AUB.

Systematic review registration

PROSPERO CRD42019137282.
Assessing consciousness in patients with disorders of consciousness using soft-clustering
Authors: Adama Sophie , Bogdan Martin
Published: July 2023

Consciousness is something we experience in our everyday life, more especially between the time we wake up in the morning and go to sleep at night, but also during the rapid eye movement (REM) sleep stage. Disorders of consciousness (DoC) are states in which a person’s consciousness is damaged, possibly after a traumatic brain injury. Completely locked-in syndrome (CLIS) patients, on the other hand, display covert states of consciousness. Although they appear unconscious, their cognitive functions are mostly intact. Only, they cannot externally display it due to their quadriplegia and inability to speak. Determining these patients’ states constitutes a challenging task. The ultimate goal of the approach presented in this paper is to assess these CLIS patients consciousness states. EEG data from DoC patients are used here first, under the assumption that if the proposed approach is able to accurately assess their consciousness states, it will assuredly do so on CLIS patients too. This method combines different sets of features consisting of spectral, complexity and connectivity measures in order to increase the probability of correctly estimating their consciousness levels. The obtained results showed that the proposed approach was able to correctly estimate several DoC patients’ consciousness levels. This estimation is intended as a step prior attempting to communicate with them, in order to maximise the efficiency of brain–computer interfaces (BCI)-based communication systems.
Short-term effect of plant-based Nordic diet versus carbohydrate-restricted diet on glucose levels in gestational diabetes – the eMOM pilot study
Authors: Markussen Lisa Torsdatter , Kivelä Jemina , Lindström Jaana , Ashrafi Reza A. , Heinonen Seppo , Koivusalo Saila , Meinilä Jelena
Published: July 2023

Background

The optimal nutritional treatment for gestational diabetes (GDM) is still a matter of debate. With increasing rates of GDM and potential negative consequences for the health of mother and child, the best treatment should be established. The Nordic diet with emphasis on plant-based protein show promising health outcomes in other populations but has yet to be investigated in GDM population. The aim of this study, which is part of the “Effect of plant-based Nordic diet versus carbohydrate-restricted diet on glucose levels in gestational diabetes” (eMOM) pilot study was to compare the short-term effects of healthy Nordic diet (HND) and the currently recommended moderate restriction of carbohydrates diet (MCRD) on glucose and lipid metabolism in women with GDM.

Methods

This was a randomized crossover where each of the diet interventions (HND and MCRD) were consumed for 3 days with a 3-day wash-out period in between. In total, 42 pregnant women diagnosed with GDM (< 29 + 0 gestational week) were randomized. Glucose data was collected by continuous glucose monitors (CGM, Freestyle Libre®, Abbott, USA) worn for 14 days, and participants gave blood samples before and after diet interventions. The primary outcome was time spent in glucose target range (TIR, < 7.8 mmol/L). TIR, 3-day mean tissue glucose as well as changes in fasting glucose, homeostatic model of insulin resistance (HOMA-IR) and blood lipids were analyzed with paired samples statistical analyses.

Results

Thirty-six women with complete 14 days CGM data were analyzed. Both diet interventions produced a high degree of TIR (99% SD 1.8), without a difference between the diets (p = 0.727). The 3-day mean glucose was significantly lower in HND than in MCRD (p = 0,049). Fasting insulin (p = 0,034), insulin resistance (p = 0,030), total and LDL cholesterol (p = 0,023 and 0,008) reduced more in the MCRD diet than the HND. NS differences in any other measure of CGM or blood tests.

Conclusions

HND and MCRD did not differ in terms of their short-term effect on TIR. A larger study with sufficient power is needed to confirm the differences in short-term mean glucose, insulin resistance and lipid metabolism.

Trial registration

Registered in clinicaltrials.gov (21/09/2018, NCT03681054).
A single, episodic event of unilateral/bilateral scrotal swelling in a group of adult boars at an Austrian boar stud
Authors: Schwarz Lukas , Dürlinger Sophie , Martin Vera , Weißenböck Herbert , Brunthaler Rene , Rümenapf Till , Auer Angelika , Loncaric Igor , Zimpernik Irene , Reisinger Nicole , Behler-Wöchtl Bettina , Scarlet Dragos , Althouse Gary , Kuster Chris , Kauffold Johannes , Segales Joaquim , Laitat Martine , Thilmant Pierre , Grahofer Alexander , Ladinig Andrea
Published: July 2023

Background

Scrotal swelling is a clinical situation which can be caused by different aetiologies. In this case report, we describe a multi-week episode of unilateral and bilateral scrotal swelling in boars at an Austrian boar stud and its diagnostic work-up.

Case presentation

In the summer of 2020, the herd veterinarian of an Austrian boar stud reported that over a period of six weeks, five out of 70 boars presented with unilateral severe swelling of the left scrotum and three out of 70 boars with bilateral severe swelling of the left and moderate swelling of the right scrotum, respectively. A complete history was obtained and an on-site evaluation of the facility was done. Five boars were necropsied, and a variety of samples harvested for further diagnostic investigations. Infectious differential diagnoses associated with unilateral swelling of the scrotum or the testis were excluded through serological and tissue testing. In three of the five boars, histopathology revealed complete acute haemorrhagic necrosis of the left testis concurrent with strongly congested blood vessels. Review of the collected information with a group of experts in the field of boar stud management resulted with consensus that, most likely, trauma was the etiologic event causing the clinical signs and pathology. Coincident with discussion of implementing video recording cameras in the boar housing area, no further clinical cases followed. As this case occurred during the first lockdown of the COVID-19 pandemic, we propose that the distress and travelling restrictions may have contributed to frustration among boar stud workers, which was consequently expressed as misbehaviour against boars.

Conclusions

Once all known infectious causes of unilateral swelling of the scrotum were excluded, a critical diagnostic work-up focused on non-infectious causes. Non-infectious causes, such as trauma, need to be carefully evaluated, as it may also include human misbehaviour against boars. Summarizing all findings of this case report, the authors hypothesize that a blunt trauma was the reason for the series of mainly unilateral swelling of the scrota of boars.