bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defining the optimal cut-point of self-reported ART adherence to achieve viral suppression in the era of contemporary HIV therapy: a cross-sectional study
Authors: O’Halloran Leach Emma , Lu Huiyin , Caballero Joshua , Thomas Jennifer E. , Spencer Emma C. , Cook Robert L. 
Published: June 2021

Abstract
Background
When considering adherence to antiretroviral therapy (ART) for HIV, many different cut-points are used. The primary goals of this study were to identify a level of self-reported medication adherence that best distinguished HIV viral suppression from non-suppression, and to compare the ability of a single-item and a 3-item adherence questionnaire to predict HIV viral suppression.

Methods
This cross-sectional analysis included 380 persons with HIV (PWH) from the Florida Cohort study who completed a self-reported ART adherence measure within 30-days of having an HIV viral load test. We used Receiver Operating Characteristic (ROC) curve analyses and ROCContrast to compare the ability of a single-item and a 3-item self-reported adherence measure to predict HIV viral suppression (defined as ≤ 200 copies/mL). We used the Youden index and chi square statistics to assess specific cut-points, and repeated the analysis with a different definition of HIV viral suppression (≤ 1000 copies/mL).

Results
The mean percent adherence was 92.4% using the single-item score and 90.4% using the 3-item score; 81.6% had viral suppression. The areas under the curve for the single-item and 3-item adherence measures were generally poor overall and not significantly different from each other (0.589 and 0.580, p = 0.67). The Youden index identified cut-points of 93% and 89% as maximizing the sensitivity and specificity for the single-item and 3-item measures, respectively, whereas a cut-point of 80% on the single-item measure was best able to discriminate those with viral suppression (58% vs. 84%, p < 0.001). Results were similar with viral suppression defined as ≤ 1000 copies/mL.

Conclusions
In this sample of PWH, a single question on medication adherence was as good as a 3-item questionnaire in predicting HIV viral suppression, although neither had good discriminatory ability. A cut-point close to 90% adherence maximized sensitivity and specificity, although viral suppression was very similar for nearly all measures above 80%.
The effect of high-definition transcranial direct current stimulation intensity on motor performance in healthy adults: a randomized controlled trial
Authors: Lerner Ohad , Friedman Jason , Frenkel-Toledo Silvi 
Published: June 2021

Abstract
Background
The results of transcranial direct current stimulation (tDCS) studies that seek to improve motor performance for people with neurological disorders, by targeting the primary motor cortex, have been inconsistent. One possible reason, among others, for this inconsistency, is that very little is known about the optimal protocols for enhancing motor performance in healthy individuals. The best way to optimize stimulation protocols for enhancing tDCS effects on motor performance by means of current intensity modulation has not yet been determined. We aimed to determine the effect of current intensity on motor performance using–for the first time–a montage optimized for maximal focal stimulation via anodal high-definition tDCS (HD-tDCS) on the right primary motor cortex in healthy subjects.

Methods
Sixty participants randomly received 20-min HD-tDCS at 1.5, 2 mA, or sham stimulation. Participants’ reaching performance with the left hand on a tablet was tested before, during, and immediately following stimulation, and retested after 24 h.

Results
In the current montage of HD-tDCS, movement time did not differ between groups in each timepoint. However, only after HD-tDCS at 1.5 mA did movement time improve at posttest as compared to pretest. This reduction in movement time from pretest to posttest was significantly greater compared to HD-tDCS 2 mA. Following HD-tDCS at 1.5 mA and sham HD-tDCS, but not 2 mA, movement time improved at retest compared to pretest, and at posttest and retest compared to the movement time during stimulation. In HD-tDCS at 2 mA, the negligible reduction in movement time from the course of stimulation to posttest was significantly lower compared to sham HD-tDCS. Across all groups, reaction time improved in retest compared to pretest and to the reaction time during stimulation, and did not differ between groups in each timepoint.

Conclusions
It appears that 2 mA in this particular experimental setup inhibited the learning effects. These results suggest that excitatory effects induced by anodal stimulation do not hold for every stimulation intensity, information that should be taken into consideration when translating tDCS use from the realm of research into more optimal neurorehabilitation.
Trial registration: Clinical Trials Gov, NCT04577768. Registered 6 October 2019 -Retrospectively registered, https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000A9B3&selectaction=Edit&uid=U0005AKF&ts=8&cx=buucf0.
The impact of PSTD on service access among people who use drugs in Vancouver, Canada
Authors: Goytan Annemarie , Lee William , Dong Huiru , Hayashi Kanna , Milloy M. J. , Kerr Thomas 
Published: June 2021

Abstract
Background
Settings throughout the United States and Canada are contending with high rates of drug-related overdose. This in turn has prompted efforts to more effectively engage people who use drugs (PWUD) in treatment and care. However, while co-morbid mental disorders are prevalent among PWUD and can undermine access to services, the impact of post-traumatic stress disorder (PTSD) on service access is not known. Therefore, we sought to assess whether PTSD is associated with difficulties accessing health and social services among PWUD in Vancouver, Canada.

Methods
Survey data was derived from two prospective cohorts of PWUD in Vancouver, Canada for the period of April 2017 to November 2018. PTSD was assessed using the PTSD Checklist for the DSM-V (PCL-5). Generalized estimating equations (GEE) was used to estimate the relationship between PTSD and self-reported inability to access health and social services, after adjustment for confounders.

Results
Among 810 participants included in our analysis, 316 (39.0%) participants qualified for a provisional PSTD diagnosis, and 117 (14.4%) reported difficulties accessing services. In a multivariable GEE analysis, a PTSD diagnosis (adjusted odds ratio = 1.69, 95% confidence interval: 1.12–2.55) was independently associated with difficulties accessing services.

Conclusions
We found high rates of PTSD and self-reported difficulties accessing services among PWUD in Vancouver, as well as a positive association between PTSD and difficulties with service access. These findings highlight the need for trauma-informed approaches to service delivery for PWUD, as well as enhanced provider training specific to PTSD.
Perspectives of illicit marijuana growers and traders on commercial legalisation of marijuana in South Africa: considerations for policy formulation
Authors: Manu Emmanuel , Douglas Mbuyiselo , Ntsaba Mohlomi Jafta , Tarkang Elvis Enowbeyang 
Published: June 2021

AbstractBackgroundOver the years, there has been a clarion call for legalising marijuana cultivation and trading for commercial purposes in South Africa. Proponents of the call argue that the criminalisation of commercial marijuana cultivation and trading has failed to halt illicit marijuana cultivation and trading. However, the views of those who economically benefit from the illicit marijuana trade on its legalisation remain empirically unsolicited.ObjectiveThis study aimed to solicit the views of illegal marijuana growers and traders from two selected communities in the Eastern Cape Province of South Africa regarding the commercial legalisation of marijuana cultivation and trading to inform policy on the debate.MethodsIn-depth key informant interview approach was used to interview 18 purposively sampled participants that were selected through the snowball sampling technique. The data were analysed using the thematic content analysis approach.ResultsParticipants had both positive and negative perceptions of the possible legalisation of marijuana cultivation and trading. On the positive side, participants indicated freedom from police, the opportunity to grow marijuana on a larger scale, capital acquisition for commercial marijuana cultivation and trading, and regulation of marijuana prices through unionisation as some of the benefits they would derive from the commercial legalisation of marijuana cultivation and trading. On the negative side, loss of their source of livelihood, fall in the price of marijuana and perceived increase in school drop-out rates were the concerns raised.ConclusionWhile participants relished improvement in their economic fortunes upon commercial legalisation of marijuana cultivation and trading, they were also apprehensive about this policy due to the perceived consequences it may have on their livelihoods and communities. We, therefore, recommend that future discussions of the commercial legalisation of marijuana cultivation and trading in South Africa should be done in consultation with illicit marijuana growers and traders to ensure that their interests are safeguarded by such a policy.
Clinical utility of Gafchromic film in an MRI-guided linear accelerator
Authors: Xhaferllari Ilma , Kim Joshua P. , Liyanage Ruchira , Liu Chang , Du Dongsu , Doemer Anthony , Chetty Indrin J. , Wen Ning 
Published: June 2021

Abstract
Background
The purpose of this study is to comprehensively evaluate the suitability of Gafchromic EBT3 and EBT-XD film for dosimetric quality assurance in 0.35 T MR-guided radiotherapy.

Methods
A 0.35 T magnetic field strength was utilized to evaluate magnetic field effects on EBT3 and EBT-XD Gafchromic films by studying the effect of film exposure time within the magnetic field using two timing sequences and film not exposed to MR, the effect of magnetic field exposure on the crystalline structure of the film, and the effect of orientation of the film with respect to the bore within the magnetic field. The orientation of the monomer crystal was qualitatively evaluated using scanning electron microscopy (SEM) compared to unirradiated film. Additionally, dosimetric impact was evaluated through measurements of a series of open field irradiations (0.83 × 0.83-cm2 to 19.92 × 19.92-cm2) and patient specific quality assurance measurements. Open fields were compared to planned dose and an independent dosimeter. Film dosimetry was applied to twenty conventional and twenty stereotactic body radiotherapy (SBRT) patient specific quality assurance cases.

Results
No visual changes in crystal orientation were observed in any evaluated SEM images nor were any optical density differences observed between films irradiated inside or outside the magnetic field for both EBT3 and EBT-XD film. At small field sizes, the average difference along dose profiles measured in film compared to the same points measured using an independent dosimeter and to predicted treatment planning system values was 1.23% and 1.56%, respectively. For large field sizes, the average differences were 1.91% and 1.21%, respectively. In open field tests, the average gamma pass rates were 99.8% and 97.2%, for 3%/3 mm and 3%/1 mm, respectively. The median (interquartile range) 3%/3 mm gamma pass rates in conventional QA cases were 98.4% (96.3 to 99.2%), and 3%/1 mm in SBRT QA cases were 95.8% (95.0 to 97.3%).

Conclusions
MR exposure at 0.35 T had negligible effects on EBT3 and EBT-XD Gafchromic film. Dosimetric film results were comparable to planned dose, ion chamber and diode measurements.
Freestyle aortic root prosthesis in combination with aortic replacement and open anastomosis: a retrospective analysis
Authors: Zientara Alicja , Rosselet-Droux Kim , Bruijnen Hans , Odavic Dragan , Genoni Michele , Dzemali Omer 
Published: June 2021

Abstract
Background
The Freestyle® bioprosthesis is used for pathologies of the aortic root. Additional resection of the ascending aorta and the proximal arch in dissections or aneurysms might be indicated. The aim was to assess mid-term outcome regarding prosthetic performance, stroke, reoperations, and survival in various pathologies comparing patients with and without additional procedures on the ascending aorta and proximal arch focusing on the standardised technique of unilateral antegrade cerebral perfusion under moderate hypothermia.

Methods
Retrospective data analysis of 278 consecutive patients after Freestyle® root replacement between September 2007 and March 2017. Patients were divided in three categories due to the pathology of the aortic root (re-operation vs endocarditis vs dissection). Two groups based on the aortic anastomosis technique (open arch anastomosis (OA) versus non-open arch anastomosis (non-OA) were compared (119 OA vs 159 non-OA). Cardiovascular risk, previous cardiac events, intra- and postoperative data were evaluated. Inferential statistics were performed with Mann-Whitney U-test. Nominal and categorical variables were tested with Fisher-Freeman-Halton exact test. Kaplan-Meier estimate was used to assess survival.

Results
The follow-up rate was 90% (median follow-up: 39.5 months). There were differences in the indication (endocarditis: OA 5 (4.2%) vs non-OA 36 (24%), p < 0.0001; dissection: OA 13 (10.9%) vs non-OA 2 (1.3%); p = 0.0007). OA patients had less perioperative stroke (1 (1%) vs 15 (10%), p = 0.001) and shorter hospital stay (9 vs 12 days, p = 0.0004). There were no differences in the mortality (in-hospital: OA 8 (7%) vs non-OA 8 (5%); p = 0.6; death at follow-up: OA 5 (5%) vs non-OA 15 (11%); p = 0.1). Overall valve performance showed a well-functioning valve in 97.3% at follow-up.

Conclusion
The valve performance showed excellent results regardless of the initial indication. The incidence of stroke was lower in patients receiving an open arch anastomosis using unilateral antegrade cerebral perfusion without elevated mortality or prolonged hospital stay.
Factor VIII replacement prophylaxis in patients with hemophilia A transitioning to adults: a systematic literature review
Authors: Sun Jing , Zhou Xuan , Hu Nan 
Published: June 2021

Abstract
Background
Despite the advantages of prophylactic treatment for hemophilia, patients tend to discontinue or not adhere to it because of several challenges such as long-term use, high cost, young patients transitioning to adolescents, and switch to self-infusion or self-care. The goal of this systematic literature review is to emphasize adherence to and efficiency of prophylactic treatment in adults.

Methods
A literature review was conducted in PubMed, Embase, and Cochrane databases until April 2021 according to PRISMA guidelines, and the protocol was registered with PROSPERO (CRD42020220085). Studies evaluating the efficacy of prophylaxis in enhancing the quality of life were included.

Results
A total of 31 articles involving 2379 patients with hemophilia were included in this systematic review. Of these, 26 studies were observational, questionnaire-based studies, and 5 were randomized controlled trials. The majority of studies reported lower annualized bleeding rates in patients receiving prophylaxis compared with those receiving on-demand treatment or those who discontinued prophylaxis. Standard-dose prophylaxis was reported to be effective in most of the studies. In developing countries like China, data suggest that low doses were administered because of limited available resources. However, standard dose or individualized prophylaxis should be provided to prevent joint damage in the long term. Compared with adults, greater adherence to treatment was observed in patients aged < 16 years.

Conclusion
This systematic review emphasizes the importance of adherence to prophylaxis among young adults transitioning from childhood. In countries like China, low-dose prophylaxis can help in preventing joint bleeds in the short term, but in the long term, standard-dose therapy has shown high adherence among young adults and better joint health, in turn improving the quality of life.
Reductions in midbrain GABAergic and dopamine neuron markers are linked in schizophrenia
Authors: Purves-Tyson Tertia D. , Brown Amelia M. , Weissleder Christin , Rothmond Debora A. , Shannon Weickert Cynthia 
Published: June 2021

AbstractReductions in the GABAergic neurotransmitter system exist across multiple brain regions in schizophrenia and encompass both pre- and postsynaptic components. While reduced midbrain GABAergic inhibitory neurotransmission may contribute to the hyperdopaminergia thought to underpin psychosis in schizophrenia, molecular changes consistent with this have not been reported. We hypothesised that reduced GABA-related molecular markers would be found in the midbrain of people with schizophrenia and that these would correlate with dopaminergic molecular changes. We hypothesised that downregulation of inhibitory neuron markers would be exacerbated in schizophrenia cases with high levels of neuroinflammation. Eight GABAergic-related transcripts were measured with quantitative PCR, and glutamate decarboxylase (GAD) 65/67 and GABAA alpha 3 (α3) (GABRA3) protein were measured with immunoblotting, in post-mortem midbrain (28/28 and 28/26 control/schizophrenia cases for mRNA and protein, respectively), and analysed by both diagnosis and inflammatory subgroups (as previously defined by higher levels of four pro-inflammatory cytokine transcripts). We found reductions (21 – 44%) in mRNA encoding both presynaptic and postsynaptic proteins, vesicular GABA transporter (VGAT), GAD1, and parvalbumin (PV) mRNAs and four alpha subunits (α1, α2, α3, α5) of the GABAA receptor in people with schizophrenia compared to controls (p < 0.05). Gene expression of somatostatin (SST) was unchanged (p = 0.485). We confirmed the reduction in GAD at the protein level (34%, p < 0.05). When stratifying by inflammation, only GABRA3 mRNA exhibited more pronounced changes in high compared to low inflammatory subgroups in schizophrenia. GABRA3 protein was expressed by 98% of tyrosine hydroxylase-positive neurons and was 23% lower in schizophrenia, though this did not reach statistical significance (p > 0.05). Expression of transcripts for GABAA receptor alpha subunits 2 and 3 (GABRA2, GABRA3) were positively correlated with tyrosine hydroxylase (TH) and dopamine transporter (DAT) transcripts in schizophrenia cases (GABRA2; r > 0.630, GABRA3; r > 0.762, all p < 0.001) but not controls (GABRA2; r < − 0.200, GABRA3; r < 0.310, all p > 0.05). Taken together, our results support a profound disruption to inhibitory neurotransmission in the substantia nigra regardless of inflammatory status, which provides a potential mechanism for disinhibition of nigrostriatal dopamine neurotransmission.
Novel epigenetic clock for fetal brain development predicts prenatal age for cellular stem cell models and derived neurons
Authors: Steg Leonard C. , Shireby Gemma L. , Imm Jennifer , Davies Jonathan P. , Franklin Alice , Flynn Robert , Namboori Seema C. , Bhinge Akshay , Jeffries Aaron R. , Burrage Joe , Neilson Grant W. A. , Walker Emma M. , Perfect Leo W. , Price Jack , McAlonan Grainne , Srivastava Deepak P. , Bray Nicholas J. , Cope Emma L. , Jones Kimberley M. , Allen Nicholas D. , Pishva Ehsan , Dempster Emma L. , Lunnon Katie , Mill Jonathan , Hannon Eilis 
Published: June 2021

AbstractInduced pluripotent stem cells (iPSCs) and their differentiated neurons (iPSC-neurons) are a widely used cellular model in the research of the central nervous system. However, it is unknown how well they capture age-associated processes, particularly given that pluripotent cells are only present during the earliest stages of mammalian development. Epigenetic clocks utilize coordinated age-associated changes in DNA methylation to make predictions that correlate strongly with chronological age. It has been shown that the induction of pluripotency rejuvenates predicted epigenetic age. As existing clocks are not optimized for the study of brain development, we developed the fetal brain clock (FBC), a bespoke epigenetic clock trained in human prenatal brain samples in order to investigate more precisely the epigenetic age of iPSCs and iPSC-neurons. The FBC was tested in two independent validation cohorts across a total of 194 samples, confirming that the FBC outperforms other established epigenetic clocks in fetal brain cohorts. We applied the FBC to DNA methylation data from iPSCs and embryonic stem cells and their derived neuronal precursor cells and neurons, finding that these cell types are epigenetically characterized as having an early fetal age. Furthermore, while differentiation from iPSCs to neurons significantly increases epigenetic age, iPSC-neurons are still predicted as being fetal. Together our findings reiterate the need to better understand the limitations of existing epigenetic clocks for answering biological research questions and highlight a limitation of iPSC-neurons as a cellular model of age-related diseases.
3,3′,5-Triiodothyroacetic acid (TRIAC) induces embryonic ζ-globin expression via thyroid hormone receptor α
Authors: Chen Huiqiao , Wang Zixuan , Yu Shanhe , Han Xiao , Deng Yun , Wang Fuhui , Chen Yi , Liu Xiaohui , Zhou Jun , Zhu Jun , Yuan Hao 
Published: June 2021

AbstractThe human ζ-globin gene (HBZ) is transcribed in primitive erythroid cells only during the embryonic stages of development. Reactivation of this embryonic globin synthesis would likely alleviate symptoms both in α-thalassemia and sickle-cell disease. However, the molecular mechanisms controlling ζ-globin expression have remained largely undefined. Moreover, the pharmacologic agent capable of inducing ζ-globin production is currently unavailable. Here, we show that TRIAC, a bioactive thyroid hormone metabolite, significantly induced ζ-globin gene expression during zebrafish embryogenesis. The induction of ζ-globin expression by TRIAC was also observed in human K562 erythroleukemia cell line and primary erythroid cells. Thyroid hormone receptor α (THRA) deficiency abolished the ζ-globin-inducing effect of TRIAC. Furthermore, THRA could directly bind to the distal enhancer regulatory element to regulate ζ-globin expression. Our study provides the first evidence that TRIAC acts as a potent inducer of ζ-globin expression, which might serve as a new potential therapeutic option for patients with severe α-thalassemia or sickle-cell disease.