bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new homozygous CACNB2 mutation has functional relevance and supports a role for calcium channels in autism spectrum disorder
Authors: Graziano Claudio , Despang Patrick , Palombo Flavia , Severi Giulia , Posar Annio , Cassio Alessandra , Pippucci Tommaso , Isidori Federica , Matthes Jan , Bonora Elena 
Published: December 2019

Abstract
BackgroundDiagnostic yield in patients with autism spectrum disorder (ASD) has improved over the last years, thanks to the introduction of whole genome arrays and next generation sequencing, but etiology is still unknown for the majority of cases. Among distinct cellular pathways, evidence implicating dysregulation of cellular calcium homeostasis in ASD pathogenesis has been accumulating, and specific mutations in voltage-gated calcium channels found in patients with autism were shown to be functionally relevant.MethodsWhole exome sequencing and Sanger sequencing were performed to identify and confirm variants in a girl with ASD, global developmental delay and precocious puberty, born of first-degree cousins. Site-directed mutagenesis was used to generate a human CaVβ2d calcium channel subunit carrying a CACNB2 mutation. Whole-cell patch-clamp recordings were performed to reveal functional effects of mutant CaVβ2d on Ba2+-currents mediated by L-type (CaV1.2) calcium channels in transiently transfected HEK-293 cells.ResultsIn an ASD patient, we identified a rare homozygous variant (p.Arg70Cys) in the CACNB2 gene coding for the auxiliary CaVβ2subunit of voltage-gated calcium channels. In a recombinant system, the CaVβ2 variant, which was not previously associated to ASD, was found to alter CaV1.2 calcium channel function by significantly affecting activation and inactivation of whole-cell Ba2+-currents.LimitationsAlthough the evidence of CACNB2 involvement in ASD is slowly accumulating, the number of reported patients is very limited. Deep clinical phenotyping and functional studies in larger sets of subjects will be instrumental to fully understand the penetrance and outcome of CACNB2 variants.ConclusionsThe p.Arg70Cys variant in CACNB2 shows functional consequences similar to other ASD-associated CaVβ2 mutations. These results support the idea of CACNB2 variations contributing to the development of ASD and hint to a rare form of Mendelian recessive autism with possible specific comorbidities.
Falciparum malaria from coastal Tanzania and Zanzibar remains highly connected despite effective control efforts on the archipelago
Authors: Morgan Andrew , Brazeau Nicholas , Ngasala Billy , Mhamilawa Lwidiko , Denton Madeline , Msellem Mwinyi , Morris Ulrika , Filer Dayne , Aydemir Ozkan , Bailey Jeffrey , Parr Jonathan , Mårtensson Andreas , Bjorkman Anders , Juliano Jonathan 
Published: December 2019

Abstract
Background: Tanzania’s Zanzibar archipelago has made significant gains in malaria control over the last decade and is a target for malaria elimination. Despite consistent implementation of effective tools since 2002, elimination has not been achieved. Importation of parasites from outside of the archipelago is thought to be an important cause of malaria’s persistence, but this paradigm has not been studied using modern genetic tools.Methods: We used whole-genome sequencing (WGS) to investigate the impact of importation, employing population genetic analyses of Plasmodium falciparum isolates from both the archipelago and mainland Tanzania. We assessed ancestry, levels of genetic diversity and differentiation, patterns of relatedness, and patterns of selection between these two populations by leveraging recent advances in deconvolution of genomes from polyclonal malaria infections.Results: We identified significant decreases in the effective population sizes in both populations in the timeframe of decreasing malaria transmission in Tanzania. Identity by descent analysis showed that parasites in the two populations shared large sections of their genomes, on the order of 5 cM, suggesting shared ancestry within the last 10 generations. Even with limited sampling,, we demonstrate a pair of isolates between the mainland and Zanzibar that are related at the expected level of half-siblings, consistent with recent importation.Conclusions: These findings suggest that importation plays an increasing role for malaria incidence on Zanzibar and demonstrate the value of genomic approaches for identifying corridors of parasite movement to the island.
Stigma and Perceived Threat Regarding Peripartum Depression among Pregnant Women in a “Pregnancy Friendly” Community
Authors: Amarasinghe Gayani , Agampodi Suneth Buddhika , Agampodi Thilini 
Published: December 2019

Abstract
Background: Peripartum depression (PPD) is identified globally as a major maternal morbidity. Stigma and underlying perceptions such as perceived threat which includes perceived severity and perceived susceptibility regarding PPD can interfere with timely identification, help seeking and, treatment acceptance, hindering efforts to control maternal mortality and morbidity due to this disease.Methods: A cross sectional study was conducted among pregnant women with a period of gestation more than 12 weeks attending field antenatal clinics in Anuradhapura district, Sri Lanka. Multistage cluster sampling with probability proportionate to size was used for sampling. Self-completed questionnaire with a vignette describing a postpartum mother with symptoms of peripartum depression (part A) and accompanied suicidal ideation (part B) was given to participants. Based on the vignette, agreement on stigma and perception statements were marked in a five point likert scale. An exploratory factor analysis was conducted on stigma statements. Including the factor scores, agreement to perception statements and selected socio-demographic variables, a logistic regression model was run to explain the perceived susceptibility.Results: Out of the 624 participants, 60.7% (n-379) perceived that they are not susceptible to develop a mental health problem during antenatal or postnatal period of the pregnancy. Though 86.2 % (n-525) had heard about PPD, its symptoms and even suicidal ideation were normalized by 55.9% (n-260) and 49.5% (n-280) of participants respectively. About 79.1% (n-468) thought that symptoms would resolve without treatment. By exploratory factor analysis on stigma statements (c2 80.376, p<.001), a two factor solution was achieved. Factors were interpreted as judgmental and nonjudgmental stigma. Mainly nonjudgmental stigma was evident among participants. Direct logistic regression for predicting the perceiving personal susceptibility to a perinatal mental illness (2 =31.474, p= 0.017, N = 329) revealed that only factor score for nonjudgmental stigma became statistically significant in the model (OR -0.691 p=0.029).Conclusion: Perceived threat from symptoms of peripartum depression and even suicidal ideation is low in this community. Presence of nonjudgmental stigma in this community also shows the need for social interventions to address these issues related to PPD and related morbidities.
Co-regulation role of endogenous hormones and transcriptomics profiling under cold stress in Tetrastigma hemsleyanum
Authors: Peng Xin , Qiu Wenyu , Wu Hao , Chen Hongjiang , Zhang Zhongyi 
Published: December 2019

Abstract
Background: Tetrastigma hemsleyanum Diels et Gilg is a valuable medicinally herb, Chilling sensitivity is the dominant environmental factor limiting the artificial domestication of the plants. Hormone-related gene regulation and hormone signaling pathways in response to cold stress in T. hemsleyanum remain unknown.Results: Some key genes involved in hormones biosynthesis, such as ZEP and NCED genes of ABA biosynthesis, GA2ox, GA3ox, and GA20ox genes of GA biosynthesis, ACO genes of ET biosynthesis were screened to be crucial in cold response. Consistently, the response of ABA and ABA/GA1+3 to cold stress was prior to that of GA1+3, ZR, ABA/IAA, and ABA/ZR. The increasing changes in ABA/GA1+3 turned to a steep decline with the extension of stress time, which might be one factor contributing to cold-sensitivity of T. hemsleyanum under prolonged stress. The cold tolerance of T. hemsleyanum would be enhanced by endogenous ABA but repressed by GA3 when each phytohormone was applied alone. The ABA-mediated promotion and GA-mediated repression of cold tolerance could both be attenuated by the co-application of the two phytohormones within 6h. When the biosynthesis of endogenous ABA and GA were inhibited by FLU and PAC, respectively, the effects of GA and ABA treatment were reversed partially.Conclusions: In summary, we present the ﬁrst study of global expression patterns of hormone-regulated transcripts in T. hemsleyanum. This study suggested that GA and ABA work antagonistically to balance the responses to cold in T. hemsleyanum. PAC, a GA biogenesis inhibitor, as well as exogenous ABA, might be potential plant growth regulators that can promote cold tolerance of T. hemsleyanum. The study also provided valuable hints in revealing a new theoretical basis and potential candidate genes that govern cold tolerance of T. hemsleyanum.
An immunoinformatic approach driven by experimental proteomics: in silico design of a subunit candidate vaccine targeting secretory proteins of Leishmania donovani amastigotes
Authors: Khan Md Anik Ashfaq , Ami Jenifar Quaiyum , Faisal Khaledul , Chowdhury Rajashree , Ghosh Prakash , Hossain Faria , Wahed Ahmed Abd El , Mondal Dinesh 
Published: December 2019

Abstract
Background Visceral leishmaniasis (VL) caused by dimorphic Leishmania species is a parasitic fatal disease with high socio-economic burden in endemic areas worldwide. Sustaining control of VL in terms of proper and prevailing immunity development is a global necessity amid unavailability of a prophylactic vaccine. Screening of experimental proteome of human disease propagating form of L. donovani (amastigote) can be more pragmatic for in silico mining of novel vaccine candidates.Methods By using an immunoinformatic approach, CD4 and CD8 T-cell specific epitopes from experimentally reported L. donovani proteins having secretory potential and increased abundance in amastigotes were screened. A chimera linked with a toll-like receptor 4 (TLR4) peptide adjuvant was constructed and evaluated for physicochemical characteristics, binding interaction with TLR4 in simulated physiological condition and the trend of immune response following hypothetical immunization.Results Selected epitopes from physiologically important L. donovani proeins were found mostly conserved in L. infantum - covering theoretically more than 98% of global population. The multi-epitope chimeric vaccine was predicted as stable, antigenic and non-allergenic. Structural analysis of vaccine-TLR4 receptor docked complex and its molecular dynamics simulation suggest sufficiently stable binding interface along with prospect of non-canonical receptor activation. Simulation dynamics of immune response following hypothetical immunization indicate active and memory B- as well as CD4 T-cell generation potential, and likely chance of a more Th1 polarized response.Conclusions The methodological approach and results from this study could facilitate more informed screening and selection of candidate antigenic proteins for entry into vaccine production pipeline in future to control human VL.
Abnormal genome-wide DNA methylation induced by cisplatin may contribute to the chemo-resistance of human small cell lung cancer
Authors: Ji Fuyun , Yu Shilong , Wu Yi , Lv Jing , Zhang Peng , Li Xiaokang , Jiang Chaowen , Zhang Ruijie , Song Liyuan , Chen Yan , Guo Ruiling , Qian Guisheng , Li Xihua 
Published: December 2019

Abstract
Background: So far, the platinum-based chemotherapy (e.g. cisplatin-etoposide doublet) is still the backbone for SCLC management due to its high respond rate both in LS-SCLC and ES-SCLC. However, cisplatin treatment often results in the development of chemo-resistance, leading to therapeutic failure and becoming the main obstacle to improve the therapeutic efficacy. Currently, little has been known about the genome-wide abnormal methylation of SCLC induced by cisplatin, which might provide prospective layouts to discover the potential genes and the signal pathways related with chemo-resistance of SCLC.
Results: A total of 58,401 sites was identified to be differentially methylated (|Δβ| ≧ 0.20) in H446/DDP cells compared with that of H446 cells, of which 25,991 genes were found to be hypomethylated and 32,410 genes were shown to be hypermethylated. KEGG enrichment displayed that the differentially hypomethylated genes were mainly gathered in MAPK signaling pathway, ECM-receptor interaction, and Focal adhesion, while the differentially hypermethylated genes were clustered in Neuroactive ligand-receptor interaction, Type I diabetes mellitus, Focal adhesion, Allograft rejection, ECM-receptor interaction, CAMs, Graft-versus-host disease, Intestinal immune network for IgA production, ARVC, and Viral myocarditis (KEGG enrichment, qvalue < 0.05). Among the 152 genes which were selected as the MDR-related candidate genes for qRT-PCR to testify whether the abnormal methylation regulated the expression of related genes at the mRNA level, 69 hypomethylated genes were revealed to be significantly increased and the other 54 hypermethylated genes evidently decreased in H446/DDP cells compared with that of H446 cells. Moreover, the upregulated genes with the hypomethylated sites were found to be mainly clustered in Pathways in cancer, MAPK signaling pathway, Cytokine-cytokine receptor interaction, and Cell adhesion molecules (CAMs), while the downregulated genes with the hypermethylated sites were mainly clustered in MAPK signaling pathway, Pathways in cancer, Melanoma, Osteoclast differentiation, and Prostate cancer.
Conclusions: Cisplatin could induce a large-scale abnormal methylation in the whole genome of SCLC. Pathways in cancer, MAPK signaling pathway, Cytokine-cytokine receptor interaction, and Cell adhesion molecules (CAMs) were most likely to be affected by cisplatin via. methylation to contribute to the development of chemo-resistance and other malignant biological behavior of SCLC cells.
Determinants of anemia in children under five years in Angola, Malawi and Senegal: A comparative study
Authors: KHULU CHRIS , Ramroop Shuan 
Published: December 2019

Abstract
Background: Anemia is defined as a condition where there is an insufficient quantity of homoglobin, hematocrit or red cell in the human body [1, 2]. Unicef (2017) report urged all countries to reduce under ve years mortality by 2030, thereof there is a need of understanding and determining factors contributing to child mortality. The significance of this study underpins the improvement in collaboration among the three countries and recommend to government the area to invest in order to meet the SDG target.Method: The current study used demographic health survey data from Angola (2016), Malawi (2016) and Senegal (2016). Using World Health Organisation (WHO) classification guidelines of anemia, the ordinal dependent variable was developed. The three categories of anemia condition used in this study are Mild (10.0 - 10.9 g/dl), Moderate (7.0 - 9.9 g/dl) and severe (<7 g/dl). Results: Gamma measure and chi-square test of independence was conducted to explore the association between anemia status and factors. The score test and Brant test were used to test the proportional odds model assumption and it was satisfied.Results from ordinal survey logistic regression model found place of residence, age of the child, wealth index, mother level of education and nutritional status to be significant factors associated with anemic condition of under five year children in all three countries. Discussion: The health institutions of Angola, Malawi and Senegal need to monitor under five years children that are suffering from malnutrition condition. The study showed that there is a high chance for under five years children to suffer from both malnutrition and anemia condition. This finding is similar to the results of the study that was conducted in Bangladesh and Burma [27, 28].Conclusion: The study identifieed place of residence, age of the child, wealth index, mother level of education and nutritional status as common factors associated with anemia in Angola, Malawi and Senegal. This nding is in agreement with that of the studies conducted by [27, 26, 36]. The results showed the necessity of collaboration between Angola, Malawi and Senegal in order to achieve the SGD target.
Paradox of HIV stigma in an integrated chronic disease care in rural South Africa: viewpoints of users and providers
Authors: Ameh Soter , D'Ambruoso Lucia , GOMEZ-OLIVE Francesc , Kahn Kathleen , Tollman Stephen , Klipstein-Grobusch Kerstin 
Published: December 2019

Abstract
Background: An integrated chronic disease management (ICDM) model was introduced by the National Department of Health in South Africa to tackle the dual burden of HIV/AIDS and non-communicable diseases. One of the aims of the ICDM model is to reduce HIV-related stigma. There is a dearth of literature on reduction of HIV stigma attributable to the ICDM model. This paper describes the viewpoints of health care users and providers on HIV stigma in an ICDM model in rural South Africa.Methods: A qualitative case study of HIV stigmatisation in the context of the implementation of an ICDM model in seven primary health care (PHC) facilities and their catchment communities was conducted in 2013 in the rural Agincourt sub-district, South Africa. Eight Focus Group Discussions were used to obtain data from 61 purposively selected participants who were 18 years and above. Seven In-Depth Interviews were conducted with the nurses-in-charge of the facilities. The transcripts were thematically analysed using MAXQDA 2018 qualitative software. The emerging themes on HIV stigma and HIV-related concerns were inductively analysed. Results: Both service providers and users perceived implementation of the ICDM model may have led to reduced HIV stigma in the facilities. On the other hand, service users and providers thought HIV stigma increased in the communities because community members thought that home-based carers visited the homes of HIV-infected people. Service users thought that routine HIV testing, intended for pregnant women as stipulated in the World Health Organization guidelines, was associated with unwanted pregnancies among adolescents who wanted to use contraceptives but refused to take a HIV test as a precondition for receiving contraceptives. Caregivers of ill persons wanted full disclosures of the HIV status of their family members to enable them to protect their health and contribute to enhancing adherence to anti-retroviral therapy of HIV-infected family members.Conclusions: Although the ICDM model was perceived to have contributed to reducing HIV stigma in the health facilities, it was associated with stigma in the communities. Remodelling the community component of the ICDM model could contribute to HIV stigma reduction in the study setting and elsewhere in South Africa.
Cohort Profile: The Nigerian HIV Geriatric Cohort Study
Authors: Kayode Gbenga Ayodele , Dakum Patrick , Avong Yohanna Kambai , Odutola Michael Kolawole , Okuma James , Nta Iboro Ekpo , Ndembi Nicaise , Mensah Charles , Khamofu Hadiza , Okonkwo Prosper , Okpanachi John Oko , Ezeanolue Echezona 
Published: December 2019

Abstract
Background: An estimated 280,000 adults aged 50 years and above live with HIV in Nigeria, a population set to increase with ART efficacy and expanding coverage. To learn how elderly people living with HIV (EPLHIV) in Nigeria fare, despite not being prioritized by the national treatment program, and to deepen knowledge for their differentiated care and achieve better outcomes, the Nigerian HIV Geriatric Cohort (NHGC) was setup. Methods: Patient-level data spanning the period 2004 to 2018, obtained from comprehensive HIV treatment hospitals, that are supported by four major PEPFAR-implementing partners in Nigeria was used. These 4 entities collaborated as member organizations of the Nigeria Implementation Science Alliance. We defined geriatric/elderly as those aged 50 years and above. From de-identified treatment records, demographic and clinical data of EPLHIV ≥50-year-old at ART initiation during the review period was extracted, merged into a single REDcap® database, and described using STATA 13. Results: A total of 101,652 unique EPLHIV entries were analysed. This cohort’s data was of 53,608 (52.7%) women, 51,037 (71.4%) of EPLHIV identified as married and 33,446 (51.1%) unemployed. Mean age was 57.1 years (SD=6.9) with average duration on ART as 4.6 years (SD=3.5). ART profile showed that 88,792 (95.7%) were on 1st-line and 55,905 (64.9%) were on TDF-based regimens. Mean-body mass index (BMI) was 23.0 kg/m2 (SD=5.4 kg/m2) with 56,010(55.1%), 19,619(19.3%) and 8844 (8.7%) showing normal (18.5kg/m2–24.9kg/m2), overweight (BMI 25- <30kg/m2) and obese (BMI ≥30kg/m2) ranges respectively. Hypertensive readings (systolic-BP >140mmHg or diastolic-BP >90mmHg) was found in 21,550 (21.2%) ELHIV records. Mean CD4 count was 420cells/µL (SD=285cells/µL) and 83,660(82.3%) had a viral load result showing <1000copies/ml. As for treatment outcomes, available records showed that 54.1% were active-in-treatment, 28.4% were lost-to-follow-up and 6.8% died. Poor population death records and aversion to autopsies makes it almost impossible to estimate AIDS-related deaths. Conclusions: The study described the clinical and non-clinical profile of EPLHIV in Nigeria. This study provides vital information for stakeholders in HIV prevention, care and treatment to understand the characteristics of EPLHIV. Findings from further analysis of this cohort will be applied to improve the quality of health of EPLHIV.