bluuebunny/crossref_metadata_2025_split huggingface dataset:
Explaining the outcomes of the ‘Clean India’ campaign: institutional behaviour and sanitation transformation in India
Authors: Curtis Val 
Published: August 2019

AbstractIntroductionWhilst many less developed countries are struggling to provide universal access to safe sanitation, in the last five years India has almost reached its target of eliminating open defaecation. The object of this study was to understand how the Indian Government effected this sanitation transformation.MethodsThe study employed interviews with 17 actors in the Government’s ‘Clean India’ programme across the national capital and four states which were analysed using a theory of change grounded in Behaviour Centred Design.ResultsThe Swachh Bharat Mission (Gramin) claims to have improved the coverage of toilets in rural India from 39% to over 95% of households between 2014 and mid 2019. From interviews with relevant actors we constructed a theory of change for the programme in which high-level political support and disruptive leadership changed environments in districts, which led to psychological changes in district officials, which, in turn, led to changed behaviour concerning sanitation programming. The Prime Minister’s setting of the ambitious goal to eliminate open defecation by the 150th birthday of Mahatma Gandhi (October 2019) galvanised government bureaucracy, while early success in 100 flagship districts reduced the scepticism of government employees, a cadre of 500 young professionals placed in districts imparted new ideas and energy, social and mass media was used to engage and motivate the public and key players, and new norms of ethical behaviour were demonstrated by leaders. As a result, district officials engaged emotionally with the programme and felt pride at their achievements in ridding villages of open defecation.ConclusionsThough many challenges remain, Governments seeking to achieve the Sustainable Development Goal of universal access to safe sanitation can emulate the success of India’s Swachh Bharat Mission.SUMMARY BOXESWhat is already known?At least 47 countries are not on track to reach the Sustainable Development Goal of universal access to safe sanitation by 2030 and some 0.6 billion people are still defecating in the open.It is not clear how governments in low income countries can be galvanised to act to resolve this pressing public health problem.What are the new findings?The experience of the Clean India programme suggests that countries can almost eliminate open defecation.The success of the programme was due to factors including: the setting of ambitious targets; the use of modern communications strategies and monitoring technology; and the provision of visible reward and recognition for employees.What do the new findings imply?Disruptive leadership is needed to create working environments where sometimes jaded civil servants are given an opportunity to make a difference.Politicians who embrace the cause of sanitation may find that there are votes in toilets.
The Impact of Pre-exposure Prophylaxis for Human Immunodeficiency Virus on Gonorrhea Prevalence
Authors: Pharaon Joe , Bauch Chris T. 
Published: August 2019

AbstractPre-exposure prophylaxis (PrEP) has been shown to be highly effective in reducing the risk of HIV infection in gay and bisexual men who have sex with men (GbMSM). However, PrEP does not protect against other sexually transmitted infections (STIs). In some populations, PrEP has also led to riskier behaviour such as reduced condom usage, with the result that the prevalence of bacterial STIs like gonorrhea has increased. Here we develop a compartmental model of the transmission of HIV and gonorrhea, and the impacts of PrEP, condom usage, STI testing frequency and potential changes in sexual risk behaviour stemming from the introduction of PrEP in a population of GbMSM. We find that introducing PrEP causes an increase in gonorrhea prevalence for a wide range of parameter values, including at the current recommended frequency of STI testing once every 3 months for individuals on PrEP. Moreover, the model predicts that a higher STI testing frequency alone is not enough to prevent a rise in gonorrhea prevalence, unless the testing frequency is increased to impractical levels. However, testing every 2 months in combination with sufficiently high condom usage by individuals on PrEP would be successful in maintaining gonorrhea prevalence at pre-PrEP levels. The results emphasize that programs making PrEP more available should be accompanied by efforts to support condom usage and frequent STI testing, in order to avoid an increase in the prevalence of gonorrhea and other bacterial STIs.
Transmission Dynamics of and Insights from the 2018-2019 Measles Outbreak in New York City: A Modeling Study
Authors: Yang Wan 
Published: August 2019

AbstractIn 2018-2019, New York City experienced the largest measles outbreak in the US in nearly three decades. To identify key factors contributing to this outbreak to aid future public health interventions, here we developed a model-inference system to infer the transmission dynamics of measles in the affected community, based on incidence data. Our results indicate that delayed vaccination of young children aged 1-4 years enabled the initial spread of measles and that increased infectious contact among this age group, likely via gatherings intended to expose unvaccinated children (i.e. “measles parties”), further aggravated the outbreak and led to widespread of measles beyond this age group. We found that around half of infants were susceptible to measles by age 1 (the age-limit to receive the first vaccine dose in the US); as such, infants experienced a large number of infections during the outbreak. We showed that without the implemented vaccination campaigns, the outbreak severity including numbers of infections and hospitalizations would be 10 times higher and predominantly affect infants and children under 4. These results suggest that recommending the first vaccine dose before age 1 and the second dose before age 4 could allow pro-vaccine parents to vaccinate and protect infants and young children more effectively, should high level of vaccine hesitancy persist. In addition, enhanced public health education is needed to reduce activities that unnecessarily expose children to measles and other infections.
Adverse childhood experiences in families with multiple members diagnosed to have psychiatric illnesses
Authors: Someshwar Amala , Holla Bharath , Agarwal Preeti Pansari , Thomas Anza , Jose Anand , Joseph Bobin , Raju Birudu , Karle Hariprasad , Muthukumaran M , Kodancha Prabhath G , Kumar Pramod , Reddy Preethi V , Nadella Ravi Kumar , Naik Sanjay T , Mitra Sayantanava , Mallappagiri Sreenivasulu , Sreeraj Vanteemar S , Balachander Srinivas , Ganesh Suhas , Murthy Pratima , Benegal Vivek , Reddy Janardhan Y. C. , Jain Sanjeev , Mahadevan Jayant , Viswanath Biju 
Published: August 2019

AbstractObjectiveAdverse Childhood Experiences (ACEs) are linked to the development of a number of psychiatric illnesses in adulthood. Our study examined the pattern of ACEs and their relation to the age of onset (AAO) of major psychiatric conditions in individuals from families that had ≥ 2 first degree relatives with major psychiatric conditions (multiplex families) identified as part of an ongoing longitudinal study.MethodsOur sample consisted of 509 individuals from 215 families. Of these, 268 were affected i.e diagnosed with bipolar disorder (BPAD) (n=61), obsessive-compulsive disorder (OCD) (n=58), schizophrenia (n=52), substance dependence (SUD) (n=59), or co-occurring diagnoses (n=38); while 241 were at-risk first degree relatives (FDRs) who were either unaffected (n=210) or had other depressive or anxiety disorders (n=31). All individuals were evaluated using the Adverse Childhood Experiences – International Questionnaire (ACE-IQ) and ACE binary and frequency scores were calculated.ResultsIt was seen that affected males, as a group, had the greatest ACE scores in our sample. A cox mixed-effects model fit by gender revealed that higher ACE binary and frequency scores were associated with significantly increased risk for an earlier AAO of psychiatric diagnoses in males. A similar model that evaluated the effect of diagnosis revealed an earlier AAO in OCD and SUD, but not in schizophrenia and BPAD.ConclusionsOur study indicates that ACEs brought forward the onset of major psychiatric conditions in men and in individuals diagnosed with OCD and SUD. Ongoing longitudinal assessments in FDRs from these families are expected to identify mechanisms underlying this relationship.
Whatman FTA®cards versus plasma specimens for the quantitation of HIV-1 RNA using two Real-Time PCR assays
Authors: Yacouba Abdourahamane , Congo Malika , Dioma Gérard Komonsira , Somlaré Hermann , Coulidiaty David , Ouattara Kalifa , Sangare Lassana 
Published: August 2019

AbstractBackgroundSeveral studies have been conducted to compare the use DBS as alternative to plasma specimens, but mainly using Whatman 903®cards as filter paper. The aim of this study was to evaluate Whatman FTA®cards (FTA cards) specimens for HIV-1 viral load testing by comparing it to plasma specimens, using 2 real-Time PCR assays.MethodologyA cross-sectional study was conducted between April 2017 and September 2017, in HIV-1 patients admitted at Yalgado Ouédraogo teaching hospital. Paired FTA cards and plasma specimens were collected and analyzed using Abbott RealTime HIV-1 assay (Abbott) and COBAS®AmpliPrep/COBAS®TaqMan v2.0 (Roche), following manufacturers’ protocol.ResultsA total of 107 patients were included. No Statistical differences (p-value > 0.05) were observed between the mean viral loads obtained from FTA cards and plasma specimens with Roche and Abbott assays. Twenty-nine samples with Roche and 15 samples with Abbott assay showed discrepant results. At viral loads of ≤1000 copies/mL, the sensitivity and specificity of FTA cards were 78.6%, and 100% with Roche, and 92.3% and 95.9% with Abbott. Strong correlation was found between FTA cards and plasma specimens with both assays. With Roche, Bland-Altman analysis showed bias of −0.3 and 95% limits of agreement of −2.6 to 1.8 log10, with 97/99 cases (97.9%) within agreement limits. With Abbott, Bland-Altman analysis showed bias of −0.1 and 95% limits of agreement of −2.3 to 2.1 log10, with 96/99 cases (96.9%) within agreement limits.ConclusionOur study demonstrated the feasibility of using FTA cards filter paper for HIV-1 viral load testing. However, further studies are required for FTA cards filter paper validation in HIV-1 treatment monitoring.
Characterization of resistance to a potent D-peptide HIV entry inhibitor
Authors: Smith Amanda R. , Weinstock Matthew T. , Siglin Amanda E. , Whitby Frank G. , Nicholas Francis J. , Hill Christopher P. , Eckert Debra M. , Root Michael J. , Kay Michael S. 
Published: August 2019

AbstractBackgroundPIE12-trimer is a highly potent D-peptide HIV-1 entry inhibitor that broadly targets group M isolates. It specifically binds the three identical conserved hydrophobic pockets at the base of the gp41 N-trimer with sub-femtomolar affinity. This extremely high affinity for the transiently exposed gp41 trimer provides a reserve of binding energy (resistance capacitor) to combat resistance via stepwise accumulation of modest affinity-disrupting mutations. Viral passaging in the presence of escalating PIE12-trimer concentrations ultimately selected for PIE12-trimer resistant populations, but required an extremely extended timeframe (>1 year) in comparison to other entry inhibitors. Eventually, HIV developed resistance to PIE12-trimer by mutating Q577 in the gp41 pocket.ResultsUsing deep sequence analysis, we identified three mutations at Q577 (R, N and K) in our two PIE12-trimer resistant pools. Each point mutant is capable of conferring the majority of PIE12-trimer resistance seen in the polyclonal pools. Surface plasmon resonance studies demonstrated substantial affinity loss between PIE12-trimer and the Q577R-mutated gp41 pocket. A high-resolution x-ray crystal structure of PIE12 bound to the Q577R pocket revealed the loss of two hydrogen bonds, the repositioning of neighboring residues, and a small decrease in buried surface area. The Q577 mutations in an NL4-3 backbone decreased viral growth rates. Fitness was ultimately rescued in resistant viral pools by a suite of compensatory mutations in gp120 and gp41, of which we identified seven candidates from our sequencing data.ConclusionsThese data show that PIE12-trimer exhibits a high barrier to resistance, as extended passaging was required to develop resistant virus with normal growth rates. The primary resistance mutation, Q577R/N/K, found in the conserved gp41 pocket, substantially decreases inhibitor affinity but also damages viral fitness. Identified candidate compensatory mutations in gp160 will be the focus of future mechanistic studies.
Long distance retrograde degeneration of the retino-geniculo-cortical pathway in homonymous hemianopia
Authors: Rajanala Alekya P. , Shariati Mohammad A. , Liao Yaping Joyce 
Published: August 2019

AbstractLong-distance retrograde degeneration of the retino-geniculo-cortical pathway has been described in humans and animal models following injury to the brain. In this study, we used optical coherence tomography (OCT) to measure the severity and timing of retrograde degeneration after post-chiasmal visual pathway lesions in patients with homonymous hemianopia. We performed a retrospective study of 69 patients with homonymous hemianopia and analyzed high quality OCT macular ganglion cell complex (GCC) and retinal nerve fiber layer (RNFL). Patients with lesions involving the optic tract and thalamus were included in the anterior group, while patients with lesions of the occipital lobe were included in the posterior group. Statistical significance was determined using Mann-Whitney U test and Wilcoxon test. We found that in patients with homonymous hemianopia, those with anterior lesion exhibited earlier and more severe thinning compared with the posterior group. In fact, thinning can occur within 2 months after insult in the anterior group. Within 6 months of onset, the anterior group exhibited about 5 times more hemi-macular GCC thinning than those with acquired lesions of the posterior visual pathway (P = 0.0023). Although the severity of hemi-macular GCC thinning was different, the majority of hemi-macular thinning occurred within the first 6 months in both groups. Beyond 2 years, thinning in those with acquired anterior and posterior lesions was minimal, except in a small number of patients with multiple insults to the occipital lobe. In conclusion, using OCT, we measured the severity and rate of long-distance, retrograde degeneration in patients with homonymous hemianopia. Homonymous hemi-macular thinning after optic tract and thalamic injury was more severe and occurred earlier compared with thinning after occipital lobe insult via trans-synaptic degeneration. The presence of severe hemi-macular degeneration on OCT provides objective evidence that localizes the lesion to the post-chiasmal anterior visual pathway.
FMO1 catalyzes the production of taurine from hypotaurine
Authors: Veeravalli Sunil , Phillips Ian R. , Freire Rafael T. , Varshavi Dorsa , Everett Jeremy R. , Shephard Elizabeth A. 
Published: August 2019

ABSTRACTTaurine is one of the most abundant amino acids in mammalian tissues. It is obtained from the diet and byde novosynthesis, from cysteic acid or hypotaurine. Despite the discovery in 1954 that the oxygenation of hypotaurine produces taurine, the identification of an enzyme catalyzing this reaction has remained elusive. In large part this is due to the incorrect assignment, in 1962, of the enzyme as a NAD-dependent hypotaurine dehydrogenase. For more than 55 years the literature has continued to refer to this enzyme as such. Here we show, bothin vivoandin vitro, that the enzyme that oxygenates hypotaurine to produce taurine is flavin-containing monooxygenase 1 (FMO1). Metabolite analysis of the urine ofFmo1-null mice by1H NMR spectroscopy revealed a build-up of hypotaurine and a deficit of taurine in comparison with the concentrations of these compounds in the urine of wild-type mice.In vitroassays confirmed that FMO1 of human catalyzes the conversion of hypotaurine to taurine utilizing either NADPH or NADH as co-factor. FMO1 has a wide substrate range and is best known as a xenobiotic- or drug-metabolizing enzyme. The identification that the endogenous molecule hypotaurine is a substrate for the FMO1-catalyzed production of taurine resolves a long-standing mystery. This finding should help establish the role FMO1 plays in a range of biological processes in which taurine or its deficiency is implicated, including conjugation of bile acids, neurotransmitter, anti-oxidant and anti-inflammatory functions, the pathogenesis of obesity and skeletal muscle disorders.
Temperature dependent sex-biased gene expression in the gametophytes of the kelpSaccharina latissima
Authors: Monteiro Cátia , Heinrich Sandra , Bartsch Inka , Valentin Klaus Ulrich , Corre Erwan , Collén Jonas , Harms Lars , Glöckner Gernot , Bischof Kai 
Published: August 2019

AbstractSaccharina latissimais an economically and ecologically relevant kelp species in Europe and North America. In kelps, the sexuality is expressed during the haploid life stage and the microscopic gametophytes exhibit significant sexual dimorphism. To understand the sex-dependent impact of temperature on the gametophyte stage, we analyzed for the first time, gene expression profiles of male and female gametophytes at three different temperatures (4°C, 12°C and 20°C) characteristic for the species distribution range by using RNA-sequencing. We identified several differentially expressed genes between sexes; while female biased genes were enriched in general metabolism and energy production, male biased genes function within cell cycle and signaling. In our study, temperature modulated sex-biased gene expression, with only a small percentage of differentially expressed genes consistently male (7%) or female-biased (12%) at the three temperatures. Female gametophytes responded stronger to higher temperatures than males, suggesting that males are more heat tolerant. Differences betweenS. latissimaand other brown algal gender-dependent gene expression might mirror the different evolutionary and ecological contexts. Genomic information on kelp gametophyte is still scarce and thus this study adds to our knowledge on sex differences in abiotic stress responses in macroalgae at the transcriptomic level.HighlightThe transcriptomic basis for sexual dimorphism and associated metabolic needs are described for the kelpSaccharina latissima. Temperature modulates sex-biased gene expression resulting in a stronger stress response in females.
Neural circuit mechanism underlying the feeding controlled by insula-central amygdala pathway
Authors: Zhang-Molina Calvin , Schmit Matthew B , Cai Haijiang 
Published: August 2019

SummaryCentral nucleus of amygdala (CeA) contains distinct populations of neurons that play opposing roles in feeding. The circuit mechanism of how CeA neurons process information sent from their upstream inputs to regulate feeding is still unclear. Here we show that activation of the neural pathway projecting from insular cortex neurons to CeA suppresses food intake. Surprisingly, we find that the inputs from insular cortex form excitatory connections with similar strength to all types of CeA neurons. To reconcile this puzzling result, and previous findings, we developed a conductance-based dynamical systems model for the CeA neuronal network. Computer simulations showed that both the intrinsic electrophysiological properties of individual CeA neurons and the overall synaptic organization of the CeA circuit play a functionally significant role in shaping the CeA neural dynamics. We successfully identified a specific CeA circuit structure that reproduces the desired circuit output consistent with existing experimentally observed feeding behaviors.
Multilevel modelling, prevalence and predictors of hypertension in Ghana: Evidence from Wave 2 of the World Health Organization’s Study on Global AGEing and adult health
Authors: Aheto Justice Moses K. , Dagne Getachew A. 
Published: August 2019

AbstractBackgroundHypertension is a major public health issue, a critical risk factor for cardiovascular diseases and stroke, especially in developing countries where the rates remain unacceptably high. In Africa, hypertension is the leading driver of cardiovascular disease and stroke deaths. Identification of critical risk factors of hypertension can help formulate targeted public health programmes and policies aimed at reducing the prevalence and its associated morbidity, disability and mortality. This study attempts to develop multilevel regression, an in-depth statistical model to identify critical risk factors of hypertension.MethodsThis study used data on 4381 individuals aged ≥18 years from the nationally representative World Health Organization Study on global AGEing and adult health (SAGE) Ghana Wave 2. Multilevel regression modelling was employed to identify critical risk factors for hypertension based on systolic blood pressure (SBP) (i.e. SBP>140mmHg).ResultsThe data on 4381 individuals were analysed out of which 27.3% were hypertensive. Critical risk factors for hypertension identified were age, obesity, marital status, health state and difficulty with self-care. Strong unobserved household-level residual variations were found.ConclusionHypertension remains high in Ghana. Addressing the problem of obesity, targeting specific interventions to those aged over 50 years, and improvement in the general health of Ghanaians are paramount to reducing the prevalence and its associated morbidity, disability and mortality. Lifestyle modification in the form of dietary intake, knowledge provision supported with strong public health message and political will could be beneficial to the management and prevention of hypertension.
Function of Pumilio Genes in Human Embryonic Stem Cells and Their Effect in Stemness and Cardiomyogenesis
Authors: Silva Isabelle Leticia Zaboroski , Robert Anny Waloski , Cabo Guillermo Cabrera , Spangenberg Lucia , Stimamiglio Marco Augusto , Dallagiovanna Bruno , Gradia Daniela Fiori , Shigunov Patrícia 
Published: August 2019

AbstractPosttranscriptional regulation plays a fundamental role in the biology of embryonic stem cells (ESCs). Many studies have demonstrated that multiple mRNAs are coregulated by one or more RNA binding proteins (RBPs) that orchestrate the expression of these molecules. A family of RBPs, known as PUF (Pumilio-FBF), is highly conserved among species and has been associated with the undifferentiated and differentiated states of different cell lines. In humans, two homologs of the PUF family have been found: Pumilio 1 (PUM1) and Pumilio 2 (PUM2). To understand the role of these proteins in human ESCs (hESCs), we first demonstrated the influence of the silencing of PUM1 and PUM2 on pluripotency genes.OCT4andNANOGmRNA levels decreased significantly with the knockdown of Pumilio, suggesting that PUMILIO proteins play a role in the maintenance of pluripotency in hESCs. Furthermore, we observed that the hESCs silenced for PUM1 and 2 exhibited an improvement in efficiency ofin vitrocardiomyogenic differentiation. Usingin silicoanalysis, we identified mRNA targets of PUM1 and PUM2 expressed during cardiomyogenesis. With the reduction of PUM1 and 2, these target mRNAs would be active and could be involved in the progression of cardiomyogenesis.