bluuebunny/crossref_metadata_2025_split huggingface dataset:
Morbidities & outcomes of a neonatal intensive care unit in a complex humanitarian conflict setting, Hajjah Yemen: 2017-2018
Authors: Eze Paul , Al-Maktari Fatoum , Alshehari Ahmed Hamood , Lawani Lucky Osaheni 
Published: July 2020

Abstract
Background
The protracted conflict in Yemen has taken a massive toll on the health system, negatively impacting the health of children, especially the most vulnerable age group; the newborns.

Methods
A 2-year retrospective study of admissions into the Neonatal Intensive Care Unit (NICU) in Al-Gomhoury Hospital Hajjah, Northwest Yemen was conducted. Data was analyzed with IBM SPSS® version 25.0 statistical software using descriptive/inferential statistics.

Results
A total of 976 newborns were eligible and included in this study; 506 preterm newborns (51.8%) and 470 term newborns (48.2%). Over half, 549 (56.3%) newborns were admitted within 24 h after birth and 681 (69.8%) newborns travelled for over 60 min to arrive at the NICU. The most common admission diagnoses were complications of prematurity (341; 34.9%), perinatal asphyxia (336; 34.4%), neonatal jaundice (187; 18.8%), and neonatal sepsis (157, 16.1%). The median length of stay in the NICU was 4 days. There were 213 neonatal deaths (Facility neonatal mortality rate was 218 neonatal deaths per 1000 livebirths); 192 (90.1%) were preterm newborns, while 177 (83.1%) were amongst newborns that travelled for more 60 min to reach the NICU. Significant predictors of neonatal deaths are preterm birth (aOR = 3.09, 95% CI: 1.26–7.59, p = 0.014 for moderate preterm neonates; aOR = 6.18, 95% CI: 2.12–18.01, p = 0.001 for very preterm neonates; and aOR = 44.59, 95% CI: 9.18–216.61, p <  0.001 for extreme preterm neonates); low birth weight (aOR = 3.67, 95% CI: 1.16–12.07, p = 0.032 for very low birth weight neonates; and aOR = 17.42, 95% CI: 2.97–102.08, p = 0.002 for extreme low birth weight neonates); and traveling for more than 60 min to arrive at the NICU (aOR = 2.32, 95% CI: 1.07–5.04, p = 0.033). Neonates delivered by Caesarean section had lower odds of death (aOR = 0.38, 95% CI 0.20–0.73, p = 0.004) than those delivered by vaginal birth.

Conclusions
Preterm newborns bear disproportionate burden of neonatal morbidity and mortality in this setting which is aggravated by difficulties in accessing early neonatal care. Community-based model of providing basic obstetric and neonatal care could augment existing health system to improve neonatal survival in Yemen.
Development of mental healthcare in Cambodia: barriers and opportunities
Authors: Parry Sarah J. , Ean Nil , Sinclair Shirley P. , Wilkinson Ewan 
Published: July 2020

Abstract
Background
Despite the increasing recognition globally of the importance of mental health for sustainable development, significant barriers remain to developing mental health services in low- and middle-income countries. This study explored the particular barriers and opportunities for developing mental health services in Cambodia and how these compared with those described in other low- and middle-income countries.

Methods
For this qualitative study, 18 experienced mental health professionals from different disciplines were selected using purposive sampling. Semi-structured interviews were carried out in Phnom Penh and thematic analysis of the data was completed.

Results
Five key themes were identified: (1) Prioritising mental health in Cambodia, (2) Strengthening collaborations between mental health stakeholders, (3) Developing a mental healthcare model appropriate for the Cambodian culture and context, (4) Increasing the quantity and (5) Improving the quality of mental healthcare. All five themes were referred to by all 18 participants and the two most repeated themes were (2) Strengthening collaborations and (5) Improving the quality of mental healthcare.

Conclusions
The themes identified in this study both corroborate previous barriers identified to developing mental health services in low- and middle-income countries and shed new light on opportunities of particular importance in Cambodia. Strengthening collaborations between key stakeholders in mental health and prioritising the quality of mental health education, training and service provision were both cited as being significant opportunities for enhancing the development of mental health services in Cambodia. These have not been widely described before as being important factors.
Roadmap to strengthen global mental health systems to tackle the impact of the COVID-19 pandemic
Authors: Maulik Pallab K. , Thornicroft Graham , Saxena Shekhar 
Published: July 2020

Abstract
Background
The COVID pandemic has been devastating for not only its direct impact on lives, physical health, socio-economic status of individuals, but also for its impact on mental health. Some individuals are affected psychologically more severely and will need additional care. However, the current health system is so fragmented and focused on caring for those infected that management of mental illness has been neglected. An integrated approach is needed to strengthen the health system, service providers and research to not only manage the current mental health problems related to COVID but develop robust strategies to overcome more long-term impact of the pandemic. A series of recommendations are outlined in this paper to help policy makers, service providers and other stakeholders, and research and research funders to strengthen existing mental health systems, develop new ones, and at the same time advance research to mitigate the mental health impact of COVID19. The recommendations refer to low, middle and high resource settings as capabilities vary greatly between countries and within countries.

Discussion
The recommendations for policy makers are focused on strengthening leadership and governance, finance mechanisms, and developing programme and policies that especially include the most vulnerable populations. Service provision should focus on accessible and equitable evidence-based community care models commensurate with the existing mental health capacity to deliver care, train existing primary care staff to cater to increased mental health needs, implement prevention and promotion programmes tailored to local needs, and support civil societies and employers to address the increased burden of mental illness. Researchers and research funders should focus on research to develop robust information systems that can be enhanced further by linking with other data sources to run predictive models using artificial intelligence, understand neurobiological mechanisms and community-based interventions to address the pandemic driven mental health problems in an integrated manner and use innovative digital solutions.

Conclusion
Urgent action is needed to strengthen mental health system in all settings. The recommendations outlined can be used as a guide to develop these further or identify new ones in relation to local needs.
Symptoms and level of functioning related to comorbidity in children and adolescents with ADHD: a cross-sectional registry study
Authors: Elwin Marie , Elvin Tove , Larsson Jan-Olov 
Published: July 2020

Abstract
Background
It is well known that a wide range of psychiatric disorders co-occur with attention deficit hyperactivity disorder. In this study we aimed to examine the associations of psychiatric comorbidity in ADHD with symptom severity and level of functioning.

Methods
We used data from the Swedish National Quality Registry for ADHD Treatment Follow-up and identified comorbid diagnoses in a sample of 3246 Swedish children and adolescents with ADHD. We investigated the association of comorbidity with symptom severity and level of function by multiple linear regressions.

Results
Autism spectrum disorder, anxiety and affective disorders, oppositional defiant disorder or conduct disorder, learning disorders, and multiple comorbid disorders associate to lower levels of functioning compared to ADHD only. Multiple comorbidity, autism spectrum disorder, oppositional defiant or conduct disorders and tic disorders relate to ADHD symptom severity.

Conclusions
Comorbidity subgroups with ADHD differ in functional impairment and ADHD symptoms severity. Information on comorbidity profiles could be used for treatment planning more adapted to the individual. Especially those who have autism spectrum disorders and multiple comorbid disorders are at risk of severe ADHD symptoms and low level of functioning.
PiggyBac mutagenesis and exome sequencing identify genetic driver landscapes and potential therapeutic targets of EGFR-mutant gliomas
Authors: Noorani Imran , de la Rosa Jorge , Choi Yoon Ha , Strong Alexander , Ponstingl Hannes , Vijayabaskar M. S. , Lee Jusung , Lee Eunmin , Richard-Londt Angela , Friedrich Mathias , Furlanetto Federica , Fuente Rocio , Banerjee Ruby , Yang Fengtang , Law Frances , Watts Colin , Rad Roland , Vassiliou George , Kim Jong Kyoung , Santarius Thomas , Brandner Sebastian , Bradley Allan 
Published: July 2020

Abstract
Background
Glioma is the most common intrinsic brain tumor and also occurs in the spinal cord. Activating EGFR mutations are common in IDH1 wild-type gliomas. However, the cooperative partners of EGFR driving gliomagenesis remain poorly understood.

Results
We explore EGFR-mutant glioma evolution in conditional mutant mice by whole-exome sequencing, transposon mutagenesis forward genetic screening, and transcriptomics. We show mutant EGFR is sufficient to initiate gliomagenesis in vivo, both in the brain and spinal cord. We identify significantly recurrent somatic alterations in these gliomas including mutant EGFR amplifications and Sub1, Trp53, and Tead2 loss-of-function mutations. Comprehensive functional characterization of 96 gliomas by genome-wide piggyBac insertional mutagenesis in vivo identifies 281 known and novel EGFR-cooperating driver genes, including Cdkn2a, Nf1, Spred1, and Nav3. Transcriptomics confirms transposon-mediated effects on expression of these genes. We validate the clinical relevance of new putative tumor suppressors by showing these are frequently altered in patients’ gliomas, with prognostic implications. We discover shared and distinct driver mutations in brain and spinal gliomas and confirm in vivo differential tumor suppressive effects of Pten between these tumors. Functional validation with CRISPR-Cas9-induced mutations in novel genes Tead2, Spred1, and Nav3 demonstrates heightened EGFRvIII-glioma cell proliferation. Chemogenomic analysis of mutated glioma genes reveals potential drug targets, with several investigational drugs showing efficacy in vitro.

Conclusion
Our work elucidates functional driver landscapes of EGFR-mutant gliomas, uncovering potential therapeutic strategies, and provides new tools for functional interrogation of gliomagenesis.
Sanfu herbal patch applied at acupoints in patients with bronchial asthma: study protocol for a randomized controlled trial
Authors: Xie Xiaoyan , Xu Danghan , Zhuang Lixing , Liu Hui , Tan Sui , Lu Yanqing , Su Meiyi , Chen Jie , Pan Haihua , Lu Lu , Xu Yiming , Liao Muxi , Xu Zhanqiong , He Jun 
Published: July 2020

Abstract
Background
Bronchial asthma is one of the most common inflammatory airway disorders. As one of the main non-drug therapies, the Sanfu herbal patch (SHP) has been widely used to treat bronchial asthma, although the evidence for its efficacy and associated mechanism are inconclusive. The objective of this trial is to clarify the clinical efficacy and safety of the SHP in the treatment of bronchial asthma in the chronic persistent or clinical remission stage and to provide high-quality data for further research.

Methods
We propose a multicentre, double-blinded, parallel, randomized, placebo-controlled clinical trial involving 4 study hospitals in China. A total of 72 eligible participants will be randomized into an SHP group and a placebo group. They will receive an SHP for 3 treatment sessions. The primary outcome will be changes in forced expiratory volume in 1 s after 3 treatment sessions. Secondary outcomes will include the following: (1) the Asthma Quality of Life Questionnaire, Asthma Control Test, and Asthma Long-term Follow-up Scale; (2) levels of Metallothionein-2 and Transgelin-2 in blood and urine; and (3) levels of IL-5, IL-13, IL-23, IL-25, and thymic stromal lymphopoietin in blood. Analysis of the data will be performed at baseline, at the end of the 2nd and 3rd treatment sessions, and at the 24-week follow-up. The safety of the SHP will be evaluated at each treatment session.

Discussion
The aims of this trial are to determine whether the SHP is more effective than placebo in the treatment of patients with bronchial asthma, as well as whether the SHP works by reducing airway inflammation and reversing bronchoconstriction.

Trial registration
Chinese Clinical Trial Registry (http://www.chictr.org.cn), ChiCTR1900024616. Registered on 19 July 2019.
High production of triterpenoids in Yarrowia lipolytica through manipulation of lipid components
Authors: Zhang Jin-Lai , Bai Qiu-Yan , Peng Yang-Zi , Fan Jie , Jin Cong-Cong , Cao Ying-Xiu , Yuan Ying-Jin 
Published: July 2020

Abstract
Background
Lupeol exhibits novel physiological and pharmacological activities, such as anticancer and immunity-enhancing activities. However, cytotoxicity remains a challenge for triterpenoid overproduction in microbial cell factories. As lipophilic and relatively small molecular compounds, triterpenes are generally secreted into the extracellular space. The effect of increasing triterpene efflux on the synthesis capacity remains unknown.

Results
In this study, we developed a strategy to enhance triterpene efflux through manipulation of lipid components in Y. lipolytica by overexpressing the enzyme Δ9-fatty acid desaturase (OLE1) and disturbing phosphatidic acid phosphatase (PAH1) and diacylglycerol kinase (DGK1). By this strategy combined with two-phase fermentation, the highest lupeol production reported to date was achieved, where the titer in the organic phase reached 381.67 mg/L and the total production was 411.72 mg/L in shake flasks, exhibiting a 33.20-fold improvement over the initial strain. Lipid manipulation led to a twofold increase in the unsaturated fatty acid (UFA) content, up to 61–73%, and an exceptionally elongated cell morphology, which might have been caused by enhanced membrane phospholipid biosynthesis flux. Both phenotypes accelerated the export of toxic products to the extracellular space and ultimately stimulated the capacity for triterpenoid synthesis, which was proven by the 5.11-fold higher ratio of extra/intracellular lupeol concentrations, 2.79-fold higher biomass accumulation and 2.56-fold higher lupeol productivity per unit OD in the modified strains. This strategy was also highly efficient for the biosynthesis of other triterpenes and sesquiterpenes, including α-amyrin, β-amyrin, longifolene, longipinene and longicyclene.

Conclusions
In conclusion, we successfully created a high-yield lupeol-producing strain via lipid manipulation. We demonstrated that the enhancement of lupeol efflux and synthesis capacity was induced by the increased UFA content and elongated cell morphology. Our study provides a novel strategy to promote the biosynthesis of valuable but toxic products in microbial cell factories.
Insights into the phylogenetic relationships and drug targets of Babesia isolates infective to small ruminants from the mitochondrial genomes
Authors: Wang Xiaoxing , Wang Jinming , Liu Junlong , Liu Aihong , He Xin , Xiang Quanjia , Li Youquan , Yin Hong , Luo Jianxun , Guan Guiquan 
Published: July 2020

Abstract
Background
Babesiosis, a tick-borne disease caused by protozoans of the genus Babesia, is widespread in subtropical and tropical countries. Mitochondria are essential organelles that are responsible for energy transduction and metabolism, calcium homeostasis and cell signaling. Mitochondrial genomes could provide new insights to help elucidate and investigate the biological features, genetic evolution and classification of the protozoans. Nevertheless, there are limited data on the mitochondrial genomes of ovine Babesia spp. in China.

Methods
Herein, we sequenced, assembled and annotated the mitochondrial genomes of six ovine Babesia isolates; analyzed the genome size, gene content, genome structure and cytochrome b (cytb) amino acid sequences and performed comparative mitochondrial genomics and phylogenomic analyses among apicomplexan parasites.

Results
The mitochondrial genomes range from 5767 to 5946 bp in length with a linear form and contain three protein-encoding genes, cytochrome c oxidase subunit 1 (cox1), cytochrome c oxidase subunit 3 (cox3) and cytb, six large subunit rRNA genes (LSU) and two terminal inverted repeats (TIR) on both ends. The cytb gene sequence analysis indicated the binding site of anti-Babesia drugs that targeted the cytochrome bc1 complex. Babesia microti and Babesia rodhaini have a dual flip-flop inversion of 184–1082 bp, whereas other Babesia spp. and Theileria spp. have one pair of TIRs, 25–1563 bp. Phylogenetic analysis indicated that the six ovine Babesia isolates were divided into two clades, Babesia sp. and Babesia motasi. Babesia motasi isolates were further separated into two small clades (B. motasi Hebei/Ningxian and B. motasi Tianzhu/Lintan).

Conclusions
The data provided new insights into the taxonomic relationships and drug targets of apicomplexan parasites.
Molecular analysis reveals a high diversity of Anopheles species in Karama, West Sulawesi, Indonesia
Authors: Davidson Jenna R. , Wahid Isra , Sudirman Rusdiyah , Small Scott T. , Hendershot Allison L. , Baskin Robert N. , Burton Timothy A. , Makuru Victoria , Xiao Honglin , Yu Xiaoyu , Troth Emma V. , Olivieri Daniel , Lizarraga Stephanny , Hasan Hajar , Arfah Andi , Yusuf Muhammad , Nur Nirwana , Syafruddin Din , Asih Puji , Lobo Neil F. 
Published: July 2020

Abstract
Background
Understanding local Anopheles species compositions and bionomic traits are vital for an effective malaria vector intervention strategy. Though eight malaria vectors, including species complexes, have been documented across the island of Sulawesi, Indonesia, a comprehensive survey linking morphological and molecular species identification has not been conducted in this global hotspot of biodiversity.

Results
Eighteen distinct species of Anopheles were molecularly identified in a 1 km2 area in Karama village, West Mamuju Province, Sulawesi. Known species included An. aconitus, An. karwari, An. peditaeniatus, An. vagus, An. barbirostris, An. tessellatus, An. nigerrimus, An. crawfordi, An. maculatus, An. flavirostris and An. kochi. Of the 18 distinct sequence groups identified through both ribosomal DNA internal transcribed spacer region 2, and mitochondrial DNA cytochrome c oxidase subunit 1 loci, 8 could not be identified to species through comparison to published sequences. The comparison of morphological and molecular identities determined that interpretations of local species compositions for primary and expected species in Karama (An. barbirostris and An. vagus) had the highest rate of accuracy (92.1% and 87.6%, respectively) when compared to molecular analysis. However, the remaining distinct sequences molecularly identified to species were identified correctly by morphological methods less frequently, from 0 to 83%.

Conclusions
Karama, Indonesia has a high diversity of Anopheles spp. The unexpected high number of Anopheles species in a small area points to possible complex transmission dynamics and limitations with vector control based on possible varying behaviors and interactions with both humans and interventions. Morphological identification of Anopheles spp. in this study was more accurate for primary and expected species than secondary or unexpected species. Finally, the inability to identify seven sequence groups to species with consensus sequences implies that future studies employing sequencing are required to clarify species compositions in the Nigerrimus Subgroup, among others, as well as their distribution and vector status. Use of molecular methods in conjunction with morphological investigations for analysis of species composition, population dynamics and bionomic characteristics is directly implicated in understanding drivers of malaria transmission, intervention effectiveness, and the pursuit of malaria elimination.
Identification and validation of a commercial cryopreservation medium for the practical preservation of Dirofilaria immitis microfilaria
Authors: Shirozu Takahiro , Soga Akira , Fukumoto Shinya 
Published: July 2020

Abstract
Background
Dirofilaria immitis is a parasitic nematode transmitted by mosquitoes and the cause of heartworm disease in dogs and dirofilariasis in humans and other mammals. The parasite is endemic worldwide. Vector stage research requires a reliable supply of D. immitis microfilariae (mf). It is believed that cryopreserved mf would retain viability and provide a powerful tool for vector stage research. However, reports on cryopreservation of D. immitis mf are limited. Therefore, this study aimed to validate commercial cryopreservation media to establish a practical, convenient and reproducible storage procedure for D. immitis mf.

Methods
Six different commercially available cryopreservation media were compared with the traditional polyvinylpyrrolidone-dimethyl sulfoxide (PVP-DMSO) preservation solution. In vitro viability of purified D. immitis mf and mf-infected total blood was analyzed using a motility assay and propidium iodide staining. In vivo infectivity of Aedes aegypti mosquitoes with cryopreserved mf was assessed using a mosquito survival test and quantifying the number of third-stage larvae (L3) after 13 days post-infection.

Results
Purified mf cryopreserved in CultureSure showed the best viability when compared to mf cryopreserved in the remaining five commercially available media and PVP-DMSO. Viability of mf in mf-infected total blood cryopreserved in CultureSure varied with the ratio of infected blood to CultureSure. Optimum results were obtained with 200 µl mf-infected blood:800 µl CultureSure. CultureSure was also the optimum medium for cryopreserving mf prior to infectivity of A. aegypti. The number of L3 was approximately the same for CultureSure cryopreserved mf (3× concentrated solution) and non-cryopreserved fresh mf.

Conclusions
CultureSure is an optimal commercial cryopreservation solution for the storage of D. immitis purified mf, mf-infected total blood, and mf used for in vivo mosquito experiments. Furthermore, this study describes an easy preservation method for clinical D. immitis-infected blood samples facilitating vector stage studies, as well as the study of macrocyclic lactone resistance in heartworms and the education of veterinarians.