bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

AbstractBackgroundUnderstanding 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.MethodsWe 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.ResultsOut 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.ConclusionThe 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

Abstract
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

Abstract
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

Abstract
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

AbstractAerobic 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

Abstract

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.