bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pre-exposure prophylaxis adherence with real-time adherence feedback and partner HIV self-testing: A pilot trial among postpartum women
Authors: Davey Dvora Leah Joseph , Dovel Kathryn , Mvududu Rufaro , Nyemba Dorothy , Mashele Nyiko , Bekker Linda-Gail , Gorbach Pamina M. , Coates Thomas J. , Myer Landon 
Published: July 2021

AbstractBackgroundPre-exposure prophylaxis (PrEP) is safe and effective in postpartum women. HIV self-testing (HIVST) for partners combined with biofeedback counselling through real-time adherence measures may improve daily PrEP use among postpartum women.MethodsBetween August 2020 and April 2021 we conducted a pilot study in one primary care clinic in Cape Town, South Africa. We randomized postpartum women who initiated PrEP in pregnancy 1:1 to the intervention group (HIVST + biofeedback counselling following urine tenofovir test) or to standard of care (facility-based HIV tests and routine counselling without biofeedback). The outcomes of interest were PrEP adherence in the past 48-72hours via urine tenofovir tests and partner HIV testing, measured 1-month after randomisation. Secondary outcomes included proportion of partners who tested for HIV and discrepancy between self-reported PrEP adherence and urine tenofovir result.FindingsWe enrolled 106 women (median age=26 years; median months postpartum=2). Almost half of women reported having sex since giving birth (48%); 76% of those reported condomless sex at last sex. At enrolment most women (72%) reported missing <2 doses in the past 7-days; 36% of women had tenofovir present in her urine (no significant differences by arm). One month after enrolment, 62% (n=33) of women in the intervention arm had tenofovir present in their urine compared to 34% (n=18) in the standard of care arm (RR=1.83; 95% CI=1.19, 2.82). Two-thirds of women in the intervention arm reported that her partner tested for HIV (66%; n=35); compared to 17% (n=9) in the standard of care arm (RR=3.89; 95% CI=2.08, 7.27). The proportion of women with a discrepant adherence result (self-reported good recent adherence with no tenofovir in urine test) was significantly lower in the intervention group (n=8; 17%) compared to the standard of care group (n=24; 46%) (RR=0.33; 95% CI=0.17, 0.67). No social or clinical adverse events were reported in the intervention arm.InterpretationIn this pilot study, HIVST for partners and biofeedback counseling increased levels of recent PrEP adherence, pointing to the importance of these interventions to support PrEP use in this population.FundingOur study is funded by Fogarty International Center (K01TW011187) with additional support from NIMH (R01MH116771). Trial registration:Clinicaltrials.gov(NCT04897737). Funders had no role in data collection or analysis.
GLIS1 regulates trabecular meshwork function and intraocular pressure and is associated with glaucoma in humans
Authors: Saidas Nair K. , Srivastava Chitrangda , Brown Robert V. , Koli Swanand , Choquet Hélène , Kang Hong Soon , Kuo Yien-Ming , Grimm Sara A. , Sutherland Caleb , Badea Alexandra , Allan Johnson G. , Zhao Yin , Yin Jie , Okamoto Kyoko , Clark Graham , Borras Teresa , Zode Gulab , Kizhatil Krishnakumar , Chakrabarti Subhabrata , John Simon W.M. , Jorgenson Eric , Jetten Anton M. 
Published: July 2021

AbstractChronically elevated intraocular pressure (IOP) is the major risk factor of primary open- angle glaucoma, a leading cause of blindness. Dysfunction of the trabecular meshwork (TM), which controls the outflow of aqueous humor (AqH) from the anterior chamber, is the major cause of elevated IOP. Here, we demonstrate that mice deficient in the Krüppel- like zinc finger transcriptional factor GLI-similar-1 (GLIS1) develop chronically elevated IOP. Magnetic resonance imaging and histopathological analysis reveal that deficiency in GLIS1 expression induces progressive degeneration of the TM, leading to inefficient AqH drainage from the anterior chamber and elevated IOP. Transcriptome and cistrome analyses identified several glaucoma- and extracellular matrix-associated genes as direct transcriptional targets of GLIS1. We also identified a significant association between GLIS1 variant rs941125 and glaucoma in humans (P=4.73x10-6), further supporting a role for GLIS1 into glaucoma etiology. Our study identifies GLIS1 as a critical regulator of TM function and maintenance, AqH dynamics, and IOP.
Gene drive that results in addiction to a temperature sensitive version of an essential gene triggers population collapse in Drosophila
Authors: Oberhofer Georg , Ivy Tobin , Hay Bruce A. 
Published: July 2021

ABSTRACTOne strategy for population suppression seeks to use gene drive to spread genes that confer conditional lethality or sterility, providing a way of combining population modification with suppression. Stimuli of potential interest could be introduced by humans, such as an otherwise benign virus or chemical, or occur naturally on a seasonal basis, such as a change in temperature. Cleave and Rescue (ClvR) selfish genetic elements use Cas9 and gRNAs to disrupt endogenous versions of an essential gene, while also including a Rescue version of the essential gene resistant to disruption. ClvR spreads by creating loss-of-function alleles of the essential gene that select against those lacking it, resulting in populations in which the Rescue provides the only source of essential gene function. In consequence, if function of the Rescue, a kind of Trojan horse now omnipresent in a population, is condition-dependent, so too will be the survival of that population. To test this idea we created a ClvR in Drosophila in which Rescue activity of an essential gene, dribble, requires splicing of a temperature-sensitive intein (TS-ClvRdbe). This element spreads to transgene fixation at 23°C, but when populations now dependent on Ts-ClvRdbe are shifted to 29°C death and sterility result in a rapid population crash. These results show that conditional population elimination can be achieved. A similar logic, in which Rescue activity is conditional, could also be used in HEG-based drive, and to bring about suppression and/or killing of specific individuals in response to other stimuli..SIGNIFICANCE STATEMENTGene drive can be used to spread traits of interest through wild populations. In some contexts the goal is to suppress or eliminate the population. In principle, one way to achieve this goal is if the trait being spread confers on carriers conditional lethality in response to an environmental stimulus that is either introduced by humans into the target area at a specific time (a virus, otherwise benign chemical; a kind of species-specific insecticide), or that occurs naturally on a seasonal basis, such as a change in temperature. Here we show that ClvR selfish elements can be used to spread a gene that confers lethality and sterility in response to increased temperature, demonstrating that conditional population elimination can be achieved.
Enzymatic and structural characterization of HAD5, an essential phosphomannomutase of malaria parasites
Authors: Frasse Philip M , Miller Justin J , Soleimani Ebrahim , Zhu Jian-She , Jakeman David L , Jez Joseph M , Goldberg Daniel E , Odom John Audrey R 
Published: July 2021

ABSTRACTThe malaria parasite Plasmodium falciparum is responsible for over 200 million infections and 400,000 deaths per year. At multiple stages during its complex life cycle, P. falciparum expresses several essential proteins tethered to its surface by glycosylphosphatidylinositol (GPI) anchors, which are critical for biological processes such as parasite egress and reinvasion of host red blood cells. Targeting this pathway therapeutically has the potential to broadly impact parasite development across several life stages. Here, we characterize an upstream component of GPI anchor biosynthesis, the putative phosphomannomutase (EC 5.4.2.8) of the parasites, HAD5 (PF3D7_1017400). We confirm the phosphomannomutase and phosphoglucomutase activity of purified recombinant HAD5. By regulating expression of HAD5 in transgenic parasites, we demonstrate that HAD5 is required for malaria parasite egress and erythrocyte reinvasion. Finally, we determine the three-dimensional crystal structure of HAD5 and identify a substrate analog that specifically inhibits HAD5, compared to orthologous human phosphomannomutases. These findings demonstrate that the GPI anchor biosynthesis pathway is exceptionally sensitive to inhibition, and that HAD5 has potential as a multi-stage antimalarial target.
Accelerating leaf area measurement using a volumetric approach
Authors: Haghshenas Abbas , Emam Yahya 
Published: July 2021

AbstractDespite the advances in the techniques of indirect estimation of leaf area, the destructive measurement approaches have still remained as the reference and the most accurate methods. However, even utilizing the modern sensors and applications usually requires the laborious and time-consuming practice of unfolding and analyzing the single leaves, separately. In the present study, a volumetric approach was tested to determine the pile leaf area based on the ratio of leaf volume divided by thickness. For this purpose, the suspension technique was used for volumetry, which is based on the simple practice and calculations of the Archimedes’ principle. The results indicated that the wheat volumetric leaf area (VLA), had an approximately 1:1 correlation with the conventionally measured optical leaf area (OLA). Exclusion of the midrib volume from calculations, did not affect the estimation error (i.e. NRMSE less than 2.61%); however, improved the slope of the linear model by about 6%. The error of sampling for determining the mean leaf thickness of the pile, was also less than 2% throughout the season. Besides, a more practical and facilitated version of the pile volumetry was tested using a Specific Gravity Bench (SGB), which is currently available as a laboratory equipment. As an important observation, which was also expectable according to the 3D shape of the leaf (i.e. expansion in a 2D plane), it was evidenced that the variations in the OLA exactly follows the pattern of the changes in the leaf volume. Accordingly, it was suggested that the relative leaf areas of various experimental treatments may be compared directly based on the volume, and independently of leaf thickness. Furthermore, no considerable difference was observed among the OLAs measured using various image resolutions (NRMSE < 0.212%); which indicates that even the current superfast scanners with low resolutions as 200 dpi may be used for a precision optical measurement of leaf area. It is expected that utilizing the reliable and simple concept of volumetric leaf area, based on which the measurement time may be independent of the sample size, facilitate the laborious practice of leaf area measurement; and consequently, improve the precision of the field experiments.
Circulating metabolic biomarkers are consistently associated with incident type 2 diabetes in Asian and European populations – a metabolomics analysis in five prospective cohorts
Authors: Seah Jowy Yi Hoong , Hong Yueheng , Cichońska Anna , Sabanayagam Charumathi , Nusinovici Simon , Wong Tien Yin , Cheng Ching-Yu , Jousilahti Pekka , Lundqvist Annamari , Perola Markus , Salomaa Veikko , Tai E. Shyong , Würtz Peter , van Dam Rob M. , Sim Xueling 
Published: July 2021

AbstractBackgroundWhile Asians have a higher risk of type 2 diabetes (T2D) than Europeans for a given BMI, it remains unclear whether the same markers of metabolic pathways are associated with diabetes.ObjectivesWe evaluated associations between metabolic biomarkers and incident T2D in three major Asian ethnic groups (Chinese, Malay, and Indian) and a European population.MethodsWe analyzed data from adult males and females of two cohorts from Singapore (n = 6,393) consisting of Chinese, Malays and Indians, and three cohorts of European-origin participants from Finland (n = 14,558). We used nuclear magnetic resonance to quantify 154 circulating metabolic biomarkers at baseline and performed logistic regression to assess associations with T2D risk adjusted for age, sex, BMI and glycaemic markers.ResultsOf the 154 metabolic biomarkers, 59 were associated with higher risk of T2D in both Asians and Europeans (P < 0.0003; Bonferroni-corrected). These included branched-chain and aromatic amino acids, the inflammatory marker glycoprotein acetyls, total fatty acids, monounsaturated fatty acids, apolipoprotein B, larger very low-density lipoprotein particle sizes, and triglycerides. In addition, 13 metabolites were associated with a lower T2D risk in both populations including omega-6 polyunsaturated fatty acids and larger high-density lipoprotein particle sizes. Associations were consistent within the Asian ethnic groups (all Phet ≥ 0.05) and largely consistent for the Asian and European populations (Phet ≥ 0.05 for 128 of 154 metabolic biomarkers).ConclusionMetabolic biomarkers across several biological pathways were consistently associated with T2D risk in Asians and Europeans.
Late surges in COVID-19 cases and varying transmission potential partially due to public health policy changes in 5 Western states, March 10, 2020-January 10, 2021
Authors: Hua Xinyi , Kehoe Aubrey R. D. , Tome Joana , Motaghi Mina , Ofori Sylvia K. , Lai Po-Ying , Ali Sheikh Taslim , Chowell Gerardo , Spaulding Anne C. , Fung Isaac Chun-Hai 
Published: July 2021

AbstractObjectiveThis study investigates how the SARS-CoV-2 transmission potential varied in North Dakota, South Dakota, Montana, Wyoming, and Idaho from March 2020 through January 2021.MethodsTime-varying reproduction numbers,Rt, of a 7-day-sliding-window and of non-overlapping-windows between policy changes were estimated utilizing the instantaneous reproduction number method. Linear regression was performed to evaluate if per-capita cumulative case-count varied across counties with different population size.ResultsThe median 7-day-sliding-windowRtestimates across the studied region varied between 1 and 1.25 during September through November 2020. Between November 13 and 18,Rtwas reduced by 14.71% (95% credible interval, CrI, [14.41%, 14.99%]) in North Dakota following a mask mandate; Idaho saw a 1.93% (95% CrI [1.87%, 1.99%]) reduction and Montana saw a 9.63% (95% CrI [9.26%, 9.98%]) reduction following the tightening of restrictions. High-population counties had higher per-capita cumulative case-count in North Dakota at four time points (June 30, August 31, October 31, and December 31, 2020). In Idaho, North Dakota, and South Dakota, there was a positive correlation between population size and per-capita weekly incident case-count, adjusted for calendar time and social vulnerability index variables.ConclusionsRtdecreased after mask mandate during the region’s case-count spike suggested reduction in SARS-CoV-2 transmission.
Primary cilia drive postnatal tidemark patterning in articular cartilage by coordinating responses to Indian Hedgehog and mechanical load
Authors: Rux Danielle , Helbig Kimberly , Han Biao , Cortese Courtney , Koyama Eiki , Han Lin , Pacifici Maurizio 
Published: July 2021

ABSTRACTArticular cartilage (AC) is essential for body movement, but is highly susceptible to degenerative diseases and has poor self-repair capacity. To improve current subpar regenerative treatment, developmental mechanisms of AC should be clarified and, specifically, how postnatal multi-zone organization is acquired. Primary cilia are cell surface organelles crucial for mammalian tissue morphogenesis and while the importance of chondrocyte primary cilia is well appreciated their specific roles in postnatal AC morphogenesis remain unclear. To explore these mechanisms, we used a murine conditional loss-of-function approach (Ift88-flox) targeting joint-lineage progenitors (Gdf5Cre) and monitored postnatal knee AC development. Joint formation and growth up to juvenile stages were largely unaffected, however mature AC (aged 2 months) exhibited disorganized extracellular matrix, decreased aggrecan and collagen II due to reduced gene expression (not increased catabolism), and marked reduction of AC modulus by 30-50%. In addition, we discovered the surprising findings that tidemark patterning was severely disrupted and accompanied alterations in hedgehog signaling that were also dependent on regional load-bearing functions of AC. Interestingly, Prg4 expression was also increased in those loaded sites. Together, our data provide evidence that primary cilia orchestrate postnatal AC morphogenesis, dictating tidemark topography, zonal matrix composition and mechanical load responses.
Severe neural tube defects due to failure of closure initiation can arise without abnormality of neuroepithelial convergent extension
Authors: Nychyk Oleksandr , Galea Gabriel L. , Molè Matteo , Savery Dawn , Greene Nicholas D.E. , Stanier Philip , Copp Andrew J. 
Published: July 2021

ABSTRACTPlanar cell polarity (PCP) signalling is vital for initiation of neural tube closure in mice, with diminished convergent extension (CE) cell movements leading to a severe form of neural tube defect (NTD), termed craniorachischisis (CRN). Some human NTDs are also associated with PCP gene mutations, but affected individuals are generally heterozygous, whereas PCP homozygosity or compound heterozygosity is needed to produce CRN in mice. This suggests human NTDs may involve other genetic or environmental factors, that interact with partial loss of PCP function. We found that reduced sulfation OF glycosaminoglycans (GAGs) interacts with heterozygosity for the Lp allele of Vangl2 (a core PCP gene), to cause CRN in mice. Here, we hypothesised that this GAG-PCP interaction may regulate convergent extension movements, and hence lead to severe NTDs in the context of only partial loss of PCP function. Both Lp and null alleles of Vangl2 gave similar findings. Culture of E8.5 embryos in the presence of chlorate (a GAG sulfation inhibitor), or enzymatic cleavage of GAG chains, led to failure of NT closure initiation in the majority of Lp/+ embryos, whereas few +/+ littermates exhibited CRN. The chlorate effect was rescued by exogenous sulphate. Surprisingly, DiO labeling of the embryonic node demonstrated no abnormality of midline axial extension in chlorate-treated Lp/+ embryos that developed CRN. In contrast, positive control Lp/Lp embryos displayed severe convergent extension defects in this assay. Morphometric analysis of the closure initiation site revealed abnormalities in the size and shape of somites that flank the closing neural tube in chlorate-treated Lp/+ embryos. We conclude that severe NTDs involving failure of closure initiation can arise by a mechanism other than faulty neuroepithelial convergent extension. Matrix-mediated expansion of somites, flanking the closing neural tube, may be required for closure initiation.
Towards a Neurometric-based Construct Validity of Trust
Authors: Chen Pin-Hao A. , Fareri Dominic , Güroğlu Berna , Delgado Mauricio R. , Chang Luke J. 
Published: July 2021

AbstractTrust is a nebulous construct central to successful cooperative exchanges and interpersonal relationships. In this study, we introduce a new approach to establishing construct validity of trust using “neurometrics”. We develop a whole-brain multivariate pattern capable of classifying whether new participants will trust a relationship partner in the context of a cooperative interpersonal investment game (n=40) with 90% accuracy and find that it also generalizes to a variant of the same task collected in a different country with 82% accuracy (n=17). Moreover, we establish the convergent and discriminant validity by testing the pattern on thirteen separate datasets (n=1,427) and find that trust is reliably related to beliefs of safety, inversely related to negative affect, but unrelated to reward, cognitive control, social perception, theory of mind, and self-referential processing. Together these results provide support for the notion that the psychological experience of trust contains elements of beliefs of reciprocation and fear of betrayal aversion. Contrary to our predictions, we found no evidence that trust is related to anticipated reward. This work demonstrates how “neurometrics” can be used to characterize the psychological processes associated with brain-based multivariate representations.
Determinants of primaquine and carboxyprimaquine exposures in children and adults withPlasmodium vivaxmalaria
Authors: Chu Cindy S , Watson James A , Phyo Aung Pyae , Win Htun Htun , Yotyingaphiram Widi , Thinraow Suradet , Soe Nay Lin , Aung Aye Aye , Wilaisrisak Pornpimon , Puaprasert Kanokpich , Imwong Mallika , Hanpithakpong Warunee , Blessborn Daniel , Tarning Joel , Proux Stéphane , Ling Clare , Nosten François H , White Nicholas J 
Published: July 2021

AbstractBackgroundPrimaquine is the only widely available drug for radical cure ofPlasmodium vivaxmalaria. There is uncertainty whether the pharmacokinetic properties of primaquine are altered significantly in childhood or not.MethodsGlucose-6-phosphate dehydrogenase normal patients with uncomplicatedP. vivaxmalaria were randomized to receive either chloroquine (25mg base/kg) or dihydroartemisinin-piperaquine (dihydroartemisinin 7mg/kg and piperaquine 55mg/kg) plus primaquine; given either as 0.5 mg base/kg/day for 14 days or 1 mg/kg/day for 7 days. Pre-dose day 7 venous plasma concentrations of chloroquine, desethylchloroquine, piperaquine, primaquine and carboxyprimaquine were measured. Methemoglobin levels were measured either daily or on days 1, 3, 6 and 13, and additionally on day 10 in the primaquine 14-day groups.ResultsDay 7 primaquine and carboxyprimaquine concentrations were available for 641 patients. After adjustment for the primaquine mg/kg daily dose, day of sampling, partner drug, and fever clearance, there was a significant non-linear relationship between age and trough primaquine and carboxyprimaquine concentrations, and day methemoglobin levels. Compared to adults 30 years of age, children 5 years of age had trough primaquine concentrations 0.53 (95% CI: 0.39-0.73) fold lower, trough carboxyprimaquine concentrations 0.45 (95% CI: 0.35-0.55) fold lower, and day 7 methemoglobin levels 0.87 (95% CI: 0.58-1.27) fold lower. Increasing concentrations of piperaquine and chloroquine and poor metabolizerCYP 2D6alleles were associated with higher day 7 primaquine and carboxyprimaquine concentrations. Higher blood methemoglobin concentrations were associated with a lower risk of recurrence.ConclusionYoung children have lower primaquine and carboxyprimaquine exposures, and lower levels of methemoglobinemia, than adults. Young children may need higher weight adjusted primaquine doses than adults.
Gender Affirming Hormone Therapy induces specific DNA methylation changes in blood
Authors: Shepherd Rebecca , Bretherton Ingrid , Pang Ken , Czajko Anna , Kim Bowon , Vlahos Amanda , Zajac Jeffrey D. , Saffery Richard , Cheung Ada , Novakovic Boris 
Published: July 2021

AbstractDNA methylation is an epigenetic mark that is influenced by underlying genetic profile, environment, and aging. It also plays a key role in female-specific X-chromosome silencing in mammals. In addition to X-linked DNA methylation, sex-specific methylation patterns are widespread across autosomal chromosomes and can be present from birth or arise over time. In individuals where gender identity and sex assigned at birth are markedly and consistently incongruent, as in the case of transgender people, feminization or masculinization may be sought through gender affirming hormone therapy (GAHT). In this study we profiled genome-wide DNA methylation in blood of transgender women and transgender men, before and during GAHT (6 months and 12 months into hormone treatment). We identified several thousand differentially methylated CpG sites (DMPs) in both people undergoing feminizing and masculinizing hormone therapy, the vast majority of which were progressive changes over time. Sex-specific DNA methylation patterns established in early development are largely refractory to change in association with GAHT. The small number of sex-DMPs that were affected by GAHT were those that become sex-specific during the lifetime, known as sex-and-age DMPs.