bluuebunny/crossref_metadata_2025_split huggingface dataset:
Self-injecting non-prescribed substances into vascular access devices: a case study of one health system’s ongoing journey from clinical concern to practice and policy response
Authors: Chase Jocelyn , Nicholson Melissa , Dogherty Elizabeth , Garrod Emma , Hill Jocelyn , Brar Rupinder , Weaver Victoria , Connors William J. 
Published: November 2022

Abstract
Background
Overdose-associated deaths and morbidity related to substance use is a global public health emergency with devastating social and economic costs. Complications of substance use are most pronounced among people who inject drugs (PWID), particularly infections, resulting in increased risk of hospitalization. PWID often require intravenous access for medical treatments such as antibiotics; however, vascular access may be limited due to the impacts of long-term self-venipuncture. While vascular access devices including peripherally inserted central catheters (PICCs) allow reliable and sustained routes of administration for indicated therapies, the use of PICCs among PWID presents unique challenges. The incidence and risks associated with self-injecting non-prescribed substances into vascular access devices (SIVAD) is one such concern for which there is limited evidence and absence of formal practice guidance.

Case presentation
We report the experience of a multidisciplinary team at a health organization in Vancouver, Canada, working to characterize the incidence, patient and healthcare provider perspectives, and overall impact of SIVAD. The case study of SIVAD begins with a patient’s perspective, including patient rationale for SIVAD, understanding of risks and the varying responses given by healthcare providers following disclosure of SIVAD. Using the limited literature available on the subject, we summarize the intersection of SIVAD and substance use and outline known and anticipated health risks. The case study is further contextualized by experience from a Vancouver in-hospital Overdose Prevention Site (OPS), where 37% of all individual visits involve SIVAD. The case study concludes by describing the systematic process by which local clinical guidance for SIVAD harm reduction was developed with stakeholder engagement, medical ethics consultation, expert consensus guideline development and implementation with staff education and planned research evaluation.

Conclusion
SIVAD is encountered with enough frequency in an urban healthcare setting in Vancouver, Canada, to warrant an organizational approach. This case study aims to enhance appreciation of SIVAD as a common and complex clinical issue with anticipated health risks. The authors conclude that using a harm reduction lens for SIVAD policy and research can provide benefit to clinicians and patients by offering a clear and a consistent healthcare response to this common issue.
Impact of antiretroviral therapy (ART) duration on ART adherence among men who have sex with men (MSM) living with HIV in Jinan of China
Authors: Jiao Kedi , Liao Meizhen , Liu Guangmei , Bi Yanmei , Zhao Xiuhong , Chen Qian , Ma Jing , Yan Yu , Cheng Chunxiao , Li Yijun , Jia Wenwen , Wang Lina , Cao Yanwen , Zhao Zhonghui , Yang Xuan , Meng Jing , Li Jianzhuo , Li Xinrui , Wang Chunmei , Kang Dianmin , Ma Wei 
Published: November 2022

Abstract
Background
Consistent and complete adherence is considered an essential requirement for patients on antiretroviral therapy (ART). This study aimed to evaluate the impact of ART duration on ART adherence, identify the trend of complete adherence, and compare the factors associated with ART adherence between short-term and long-term ART group among men who have sex with men (MSM) living with HIV in Jinan of China.

Methods
MSM living with HIV aged 18 or above and currently on ART were recruited from October to December 2020 using convenience sampling. Univariate and multivariable logistic regressions were used to evaluate the impact of ART duration on adherence and compare factors associated with ART adherence between subgroups. The Mann–Kendall test was used to identify the trend of complete adherence.

Results
A total of 585 participants were included in analysis, consisting of 352 on short-term ART (ART initiation ≤ 3 years) and 233 on long-term ART (ART initiation > 3 years). Significant difference of complete ART adherence between short-term and long-term ART group was detected (79.8% vs. 69.1%, P = 0.003). Multivariable analysis showed that men with longer ART duration were less likely to report complete ART adherence (AOR = 0.88, 95% CI 0.81–0.95). A descending trend of complete adherence was identified (Z = 1.787, P = 0.037). Alcohol use and lack of medication reminders were barriers to complete adherence for both of the subgroups.

Conclusions
Sustained efforts to encourage maintaining adherence for a lifetime are necessary, especially for those on long-term ART. Future interventions should be tailored to subgroups with different ART duration and individuals with specific characteristics.
Introducing new plan evaluation indices for prostate dose painting IMRT plans based on apparent diffusion coefficient images
Authors: Moradi Saman , Hashemi Bijan , Bakhshandeh Mohsen , Banaei Amin , Mofid Bahram 
Published: November 2022

Abstract
Background
Dose painting planning would be more complicated due to different levels of prescribed doses and more complex evaluation with conventional plan quality indices considering uniform dose prescription. Therefore, we tried to introduce new indices for evaluating the dose distribution conformity and homogeneity of treatment volumes based on the tumoral cell density and relative volumes of each lesion in prostate IMRT.

Methods
CT and MRI scans of 20 male patients having local prostate cancer were used for IMRT DP planning. Apparent diffusion coefficient (ADC) images were imported to a MATLAB program to identify lesion regions based on ADC values automatically. Regions with ADC values lower than 750 mm2/s and regions with ADC values higher than 750 and less than 1500 mm2/s were considered CTV70Gy (clinical tumor volume with 70 Gy prescribed dose), and CTV60Gy, respectively. Other regions of the prostate were considered as CTV53Gy. New plan evaluation indices based on evaluating the homogeneity (IOE(H)), and conformity (IOE(C)) were introduced, considering the relative volume of each lesion and cellular density obtained from ADC images. These indices were compared with conventional homogeneity and conformity indices and IOEs without considering cellular density. Furthermore, tumor control probability (TCP) was calculated for each patient, and the relationship of the assessed indices were evaluated with TCP values.

Results
IOE (H) and IOE (C) with considering cellular density had significantly lower values compared to conventional indices and IOEs without considering cellular density. (P < 0.05). TCP values had a stronger relationship with IOE(H) considering cell density (R2 = -0.415), and IOE(C) without considering cell density (R2 = 0.624).

Conclusion
IOE plan evaluation indices proposed in this study can be used for evaluating prostate IMRT dose painting plans. We suggested to consider cell densities in the IOE(H) calculation formula and it’s appropriate to calculate IOE(C) without considering cell density values.
Fluid balance and renal replacement therapy initiation strategy: a secondary analysis of the STARRT-AKI trial
Authors: Wald Ron , Kirkham Brian , daCosta Bruno R. , Ghamarian Ehsan , Adhikari Neill K. J. , Beaubien-Souligny William , Bellomo Rinaldo , Gallagher Martin P. , Goldstein Stuart , Hoste Eric A. J. , Liu Kathleen D. , Neyra Javier A. , Ostermann Marlies , Palevsky Paul M. , Schneider Antoine , Vaara Suvi T. , Bagshaw Sean M. 
Published: November 2022

Abstract
Background
Among critically ill patients with acute kidney injury (AKI), earlier initiation of renal replacement therapy (RRT) may mitigate fluid accumulation and confer better outcomes among individuals with greater fluid overload at randomization.

Methods
We conducted a pre-planned post hoc analysis of the STandard versus Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial. We evaluated the effect of accelerated RRT initiation on cumulative fluid balance over the course of 14 days following randomization using mixed models after censoring for death and ICU discharge. We assessed the modifying effect of baseline fluid balance on the impact of RRT initiation strategy on key clinical outcomes. Patients were categorized in quartiles of baseline fluid balance, and the effect of accelerated versus standard RRT initiation on clinical outcomes was assessed in each quartile using risk ratios (95% CI) for categorical variables and mean differences (95% CI) for continuous variables.

Results
Among 2927 patients in the modified intention-to-treat analysis, 2738 had available data on baseline fluid balance and 2716 (92.8%) had at least one day of fluid balance data following randomization. Over the subsequent 14 days, participants allocated to the accelerated strategy had a lower cumulative fluid balance compared to those in the standard strategy (4509 (− 728 to 11,698) versus 5646 (0 to 13,151) mL, p = 0.03). Accelerated RRT initiation did not confer greater 90-day survival in any of the baseline fluid balance quartiles (quartile 1: RR 1.11 (95% CI 0.92 to 1.34), quartile 2: RR 1.03 (0.87 to 1.21); quartile 3: RR 1.08 (95% CI 0.91 to 1.27) and quartile 4: RR 0.87 (95% CI 0.73 to 1.03), p value for trend 0.08).

Conclusions
Earlier RRT initiation in critically ill patients with AKI conferred a modest attenuation of cumulative fluid balance. Nonetheless, among patients with greater fluid accumulation at randomization, accelerated RRT initiation did not have an impact on all-cause mortality.
Trial registration: ClinicalTrials.gov number, https://clinicaltrials.gov/ct2/show/NCT02568722, registered October 6, 2015.
m6A RNA methylation impairs gene expression variability and reproductive thermotolerance in Arabidopsis
Authors: Wang Ling , Zhuang Haiyan , Fan Wenwen , Zhang Xia , Dong Haihong , Yang Hongxing , Cho Jungnam 
Published: November 2022

AbstractHeat-imposed crop failure is often attributed to reduced thermotolerance of floral tissues; however, the underlying mechanism remains unknown. Here, we demonstrate that m6A RNA methylation increases in Arabidopsis flowers and negatively regulates gene expression variability. Stochastic gene expression provides flexibility to cope with environmental stresses. We find that reduced transcriptional fluctuation is associated with compromised activation of heat-responsive genes. Moreover, disruption of an RNA demethylase AtALKBH10B leads to lower gene expression variability, suppression of heat-activated genes, and strong reduction of plant fertility. Our work proposes a novel role for RNA methylation in the bet-hedging strategy of heat stress response.
Illuminating links between cis-regulators and trans-acting variants in the human prefrontal cortex
Authors: Liu Shuang , Won Hyejung , Clarke Declan , Matoba Nana , Khullar Saniya , Mu Yudi , Wang Daifeng , Gerstein Mark 
Published: November 2022

AbstractBackgroundNeuropsychiatric disorders afflict a large portion of the global population and constitute a significant source of disability worldwide. Although Genome-wide Association Studies (GWAS) have identified many disorder-associated variants, the underlying regulatory mechanisms linking them to disorders remain elusive, especially those involving distant genomic elements. Expression quantitative trait loci (eQTLs) constitute a powerful means of providing this missing link. However, most eQTL studies in human brains have focused exclusively on cis-eQTLs, which link variants to nearby genes (i.e., those within 1 Mb of a variant). A complete understanding of disease etiology requires a clearer understanding of trans-regulatory mechanisms, which, in turn, entails a detailed analysis of the relationships between variants and expression changes in distant genes.MethodsBy leveraging large datasets from the PsychENCODE consortium, we conducted a genome-wide survey of trans-eQTLs in the human dorsolateral prefrontal cortex. We also performed colocalization and mediation analyses to identify mediators in trans-regulation and use trans-eQTLs to link GWAS loci to schizophrenia risk genes.ResultsWe identified ~80,000 candidate trans-eQTLs (at FDR<0.25) that influence the expression of ~10K target genes (i.e., “trans-eGenes”). We found that many variants associated with these candidate trans-eQTLs overlap with known cis-eQTLs. Moreover, for >60% of these variants (by colocalization), the cis-eQTL’s target gene acts as a mediator for the trans-eQTL SNP's effect on the trans-eGene, highlighting examples of cis-mediation as essential for trans-regulation. Furthermore, many of these colocalized variants fall into a discernable pattern wherein cis-eQTL’s target is a transcription factor or RNA-binding protein, which, in turn, targets the gene associated with the candidate trans-eQTL. Finally, we show that trans-regulatory mechanisms provide valuable insights into psychiatric disorders: beyond what had been possible using only cis-eQTLs, we link an additional 23 GWAS loci and 90 risk genes (using colocalization between candidate trans-eQTLs and schizophrenia GWAS loci).ConclusionsWe demonstrate that the transcriptional architecture of the human brain is orchestrated by both cis- and trans-regulatory variants and found that trans-eQTLs provide insights into brain-disease biology.
Whole-exome sequencing identifies novel protein-altering variants associated with serum apolipoprotein and lipid concentrations
Authors: Sandholm Niina , Hotakainen Ronja , Haukka Jani K. , Jansson Sigfrids Fanny , Dahlström Emma H. , Antikainen Anni A. , Valo Erkka , Syreeni Anna , Kilpeläinen Elina , Kytölä Anastasia , Palotie Aarno , Harjutsalo Valma , Forsblom Carol , Groop Per-Henrik ,   on behalf of the FinnDiane Study Group
Published: November 2022

Abstract
Background
Dyslipidemia is a major risk factor for cardiovascular disease, and diabetes impacts the lipid metabolism through multiple pathways. In addition to the standard lipid measurements, apolipoprotein concentrations provide added awareness of the burden of circulating lipoproteins. While common genetic variants modestly affect the serum lipid concentrations, rare genetic mutations can cause monogenic forms of hypercholesterolemia and other genetic disorders of lipid metabolism. We aimed to identify low-frequency protein-altering variants (PAVs) affecting lipoprotein and lipid traits.

Methods
We analyzed whole-exome (WES) and whole-genome sequencing (WGS) data of 481 and 474 individuals with type 1 diabetes, respectively. The phenotypic data consisted of 79 serum lipid and apolipoprotein phenotypes obtained with clinical laboratory measurements and nuclear magnetic resonance spectroscopy.

Results
The single-variant analysis identified an association between the LIPC p.Thr405Met (rs113298164) and serum apolipoprotein A1 concentrations (p=7.8×10−8). The burden of PAVs was significantly associated with lipid phenotypes in LIPC, RBM47, TRMT5, GTF3C5, MARCHF10, and RYR3 (p<2.9×10−6). The RBM47 gene is required for apolipoprotein B post-translational modifications, and in our data, the association between RBM47 and apolipoprotein C-III concentrations was due to a rare 21 base pair p.Ala496-Ala502 deletion; in replication, the burden of rare deleterious variants in RBM47 was associated with lower triglyceride concentrations in WES of >170,000 individuals from multiple ancestries (p=0.0013). Two PAVs in GTF3C5 were highly enriched in the Finnish population and associated with cardiovascular phenotypes in the general population. In the previously known APOB gene, we identified novel associations at two protein-truncating variants resulting in lower serum non-HDL cholesterol (p=4.8×10−4), apolipoprotein B (p=5.6×10−4), and LDL cholesterol (p=9.5×10−4) concentrations.

Conclusions
We identified lipid and apolipoprotein-associated variants in the previously known LIPC and APOB genes, as well as PAVs in GTF3C5 associated with LDLC, and in RBM47 associated with apolipoprotein C-III concentrations, implicated as an independent CVD risk factor. Identification of rare loss-of-function variants has previously revealed genes that can be targeted to prevent CVD, such as the LDL cholesterol-lowering loss-of-function variants in the PCSK9 gene. Thus, this study suggests novel putative therapeutic targets for the prevention of CVD.
Repeated cardiopulmonary performance measurements in young competitive handball players with and without SARS-CoV-2 infection
Authors: Lässing Johannes , Kwast S. , Bischoff C. , Hölldobler N. , Vondran M. , Falz R. , Busse M. 
Published: November 2022

Abstract
Background
The SARS-CoV-2 virus and its long-term consequences in adolescents have a global impact on upcoming medical issues. The aim of this study was to investigate the effects of a SARS-CoV-2 infection on cardiorespiratory parameters in young athletes.

Methods
In a cohort study involving repeated measurements during a six-month period, cardiorespiratory parameters were assessed in infected (SCoV) and non-infected (noSCoV) athletes. We evaluated handball players (17.2 ± 1.0 years) via performance diagnostics and a specific examination after a SARS-CoV-2 infection or without.

Results
We observed no significant differences between the two groups at the first visit. But between the first and second visit, the SCoV group’s maximum power output was significantly lower than the noSCoV group’s (− 48.3 ± 12.5; p ≤ 0.01 vs. − 15.0 ± 26.0 W; p = 0.09). At the second visit, lung diffusion capacity (DLCO/VA, %predicted) did not differ between groups (111.6 ± 11.5 vs. 116.1 ± 11.8%; p = 0.45). HR during comparative stress showed no group differences. The SCoV group’s mean oxygen uptake during incremental exercise was lower (Two-way-ANOVA: 1912 vs. 2106 ml; p ≤ 0.01; mean difference: − 194 ml; 95% CI − 317 to − 71); we also noted a significantly lower stroke volume course during exercise (Two-way-ANAOVA: 147.5 vs. 169.5 ml; mean difference: − 22 ml; p ≤ 0.01; 95% CI − 34.2 to − 9.9). The probability of premature ventricular complexes after a SARS-CoV-2 infection yielded an odds ratio of 1.6 (95% CI 0.24–10.81).

Conclusions
The physical performance of young athletes infected with SARS-CoV-2 was impaired. This decreased performance is probably due to cardiac and/or peripheral deconditioning. Studies with larger cohorts are needed to make more profound conclusions.
Daytime fluctuations of endurance performance in young soccer players: a randomized cross-over trial
Authors: Fiedler Janis , Altmann Stefan , Chtourou Hamdi , Engel Florian A. , Neumann Rainer , Woll Alexander 
Published: November 2022

AbstractObjectivesFluctuations of physical performance and biological responses during a repetitive daily 24-h cycle are known as circadian rhythms. These circadian rhythms can influence the optimal time of day for endurance performance and related parameters which can be crucial in a variety of sports disciplines. The current study aimed to evaluate the daytime variations in endurance running performance in a 3.000-m field run and endurance running performance, blood lactate levels, and heart rate in an incremental treadmill test in adolescent soccer players.ResultsIn this study, 15 adolescent male soccer players (age: 18.0 ± 0.6 years) performed a 3.000-m run and an incremental treadmill test at 7:00–8:00 a.m. and 7:00–8:00 p.m. in a randomized cross-over manner. No significant variations after a Bonferroni correction were evident in endurance running performance, perceived exertion, blood lactate levels, and heart rates between the morning and the evening. Here, the largest effect size was observed for maximal blood lactate concentration (9.15 ± 2.18 mmol/l vs. 10.64 ± 2.30 mmol/l,p = .110, ES = 0.67). Therefore, endurance running performance and physiological responses during a field-based 3.000-m run and a laboratory-based test in young male soccer players indicated no evidence for daytime variations.
Subclinical binge eating symptoms in early adolescence and its preceding and concurrent factors: a population-based study
Authors: Derks Ivonne P. M. , Harris Holly A. , Staats Soundry , Gaillard Romy , Dieleman Gwen C. , Llewellyn Clare H. , Swanson Sonja A. , Jansen Pauline W. 
Published: November 2022

AbstractObjectiveBinge eating, loss of control eating and overeating often develop during late childhood or early adolescence. Understanding the presentation of binge eating as early as symptoms manifest and its preceding and concurrent factors is essential to hamper the development of eating disorders. This study examined the prevalence, concurrent and preceding factors (e.g. compensatory behaviors, emotional and behavioral problems) of subclinical binge eating symptoms in early adolescence.MethodsData from the population-based Generation R Study were used (n = 3595). At 10 years and 14 years, preceding and concurrent factors including eating behaviors, body dissatisfaction, emotional and behavioral problems and body composition were assessed. At 14 years, 3595 adolescents self-reported on binge eating symptoms in the past 3 months and were categorized into four groups: no symptoms (n = 3143, 87.4%), overeating only (n = 121, 3.4%), loss of control (LOC) eating only (n = 252, 7.0%) or binge eating (i.e. both, n = 79, 2.2%).ResultsIn total, 452 (12.6%) young adolescents reported subclinical binge eating symptoms. Those who reported LOC eating and binge eating showed most compensatory behaviors (e.g. hide or throw away food, skipping meals). Concurrent emotional and behavioral problems, body dissatisfaction, more emotional-, restrained- and uncontrolled eating, and a higher BMI were associated with subclinical binge eating symptoms. Preceding self-reported emotional and behavioral problems, body dissatisfaction, more restrained eating and higher BMI (both fat mass and fat-free mass) at 10 years were associated with LOC eating and binge eating, but not with overeating.DiscussionAmong young adolescents, subclinical binge eating symptoms were common. Considering the high prevalence of LOC eating, and the overlapping preceding and concurrent factors of LOC eating and binge eating compared to overeating, LOC eating seems to be a key symptom of binge eating in early adolescence.
blf and the drl cluster synergistically regulate cell fate commitment during zebrafish primitive hematopoiesis
Authors: Zhang Xue , Yang Yuxi , Wei Yuxuan , Zhao Qingshun , Lou Xin 
Published: November 2022

ABSTRACT
Hematopoiesis is a highly coordinated process that generates all the body's blood cells, and perturbations in embryonic hematopoiesis may result in illnesses ranging from fetal anemia to various leukemias. Correct establishment of hematopoietic progenitor cell fate is essential for the development of adequate blood cell subpopulations, although regulators of cell fate commitment have not been fully defined. Here, we show that primary erythropoiesis and myelopoiesis in zebrafish embryos are synergistically regulated by blf and the drl cluster, as simultaneous depletion led to severe erythrocyte aplasia and excessive macrophage formation at the expense of neutrophil development. Integrative analysis of transcriptome- and genome-wide binding data revealed that blf and drl cluster genes are responsible for constraining the expression of vasculogenesis-promoting genes in the intermediate cell mass and monocytopoiesis-promoting genes in the rostral blood island. This indicates that blf and drl cluster genes act as determinants of the fate commitment of erythroid and myeloid progenitor cells. Furthermore, a rescue screen demonstrated that Zfp932 is a potential mammalian functional equivalent to zebrafish blf and drl cluster genes. Our data provide insight into conserved cell fate commitment mechanisms of primitive hematopoiesis.