bluuebunny/crossref_metadata_2025_split huggingface dataset:
First confirmatory study on PTPRQ as an autosomal dominant non-syndromic hearing loss gene
Authors: Oziębło Dominika , Sarosiak Anna , Leja Marcin L. , Budde Birgit S. , Tacikowska Grażyna , Di Donato Nataliya , Bolz Hanno J. , Nürnberg Peter , Skarżyński Henryk , Ołdak Monika 
Published: October 2019

Abstract

Background
Biallelic PTPRQ pathogenic variants have been previously reported as causative for autosomal recessive non-syndromic hearing loss. In 2018 the first heterozygous PTPRQ variant has been implicated in the development of autosomal dominant non-syndromic hearing loss (ADNSHL) in a German family. The study presented the only, so far known, PTPRQ pathogenic variant (c.6881G>A) in ADNSHL. It is located in the last PTPRQ coding exon and introduces a premature stop codon (p.Trp2294*).

Methods
A five-generation Polish family with ADNSHL was recruited for the study (n = 14). Thorough audiological, neurotological and imaging studies were carried out to precisely define the phenotype. Genomic DNA was isolated from peripheral blood samples or buccal swabs of available family members. Clinical exome sequencing was conducted for the proband. Family segregation analysis of the identified variants was performed using Sanger sequencing. Single nucleotide polymorphism array on DNA samples from the Polish and the original German family was used for genome-wide linkage analysis.

Results
Combining clinical exome sequencing and family segregation analysis, we have identified the same (NM_001145026.2:c.6881G>A, NP_001138498.1:p.Trp2294*) PTPRQ alteration in the Polish ADNSHL family. Using genome-wide linkage analysis, we found that the studied family and the original German family derive from a common ancestor. Deep phenotyping of the affected individuals showed that in contrast to the recessive form, the PTPRQ-related ADNSHL is not associated with vestibular dysfunction. In both families ADNSHL was progressive, affected mainly high frequencies and had a variable age of onset.

Conclusion
Our data provide the first confirmation of PTPRQ involvement in ADNSHL. The finding strongly reinforces the inclusion of PTPRQ to the small set of genes leading to both autosomal recessive and dominant hearing loss.
Dasatinib regulates LPS-induced microglial and astrocytic neuroinflammatory responses by inhibiting AKT/STAT3 signaling
Authors: Ryu Ka-Young , Lee Hyun-ju , Woo Hanwoong , Kang Ri-Jin , Han Kyung-Min , Park HyunHee , Lee Sang Min , Lee Ju-Young , Jeong Yoo Joo , Nam Hyun-Wook , Nam Youngpyo , Hoe Hyang-Sook 
Published: October 2019

AbstractBackgroundThe FDA-approved small-molecule drug dasatinib is currently used as a treatment for chronic myeloid leukemia (CML). However, the effects of dasatinib on microglial and/or astrocytic neuroinflammatory responses and its mechanism of action have not been studied in detail.MethodsBV2 microglial cells, primary astrocytes, or primary microglial cells were treated with dasatinib (100 or 250 nM) or vehicle (1% DMSO) for 30 min or 2 h followed by lipopolysaccharide (LPS; 200 ng/ml or 1 μg/ml) or PBS for 5.5 h. RT-PCR, real-time PCR; immunocytochemistry; subcellular fractionation; and immunohistochemistry were subsequently conducted to determine the effects of dasatinib on LPS-induced neuroinflammation. In addition, wild-type mice were injected with dasatinib (20 mg/kg, intraperitoneally (i.p.) daily for 4 days or 20 mg/kg, orally administered (p.o.) daily for 4 days or 2 weeks) or vehicle (4% DMSO + 30% polyethylene glycol (PEG) + 5% Tween 80), followed by injection with LPS (10 mg/kg, i.p.) or PBS. Then, immunohistochemistry was performed, and plasma IL-6, IL-1β, and TNF-α levels were analyzed by ELISA.ResultsDasatinib regulates LPS-induced proinflammatory cytokine and anti-inflammatory cytokine levels in BV2 microglial cells, primary microglial cells, and primary astrocytes. In BV2 microglial cells, dasatinib regulates LPS-induced proinflammatory cytokine levels by regulating TLR4/AKT and/or TLR4/ERK signaling. In addition, intraperitoneal injection and oral administration of dasatinib suppress LPS-induced microglial/astrocyte activation, proinflammatory cytokine levels (including brain and plasma levels), and neutrophil rolling in the brains of wild-type mice.ConclusionsOur results suggest that dasatinib modulates LPS-induced microglial and astrocytic activation, proinflammatory cytokine levels, and neutrophil rolling in the brain.
CD147 as a key mediator of the spleen inflammatory response in mice after focal cerebral ischemia
Authors: Jin Rong , Zhong Wei , Liu Shan , Li Guohong 
Published: October 2019

AbstractBackgroundThe splenic inflammatory response after cerebral ischemia has been implicated in secondary brain injury. We have recently reported that CD147 plays an important role in driving brain inflammation after ischemic stroke. In this study, we hypothesized that CD147 may play a role in the splenic inflammatory response after cerebral ischemia.MethodsTransient (60 min) middle cerebral artery occlusion was induced in wild-type mice treated with an anti-CD147 antibody (αCD147) 1 h before ischemia onset. The splenic inflammatory response was evaluated at 4 and 24 h, representing the peak and early stage of splenic inflammatory activation in this model. Changes in mRNA and protein expression of CD147 and inflammatory markers were measured using RT-qPCR and western blot, respectively. Immune cells in the spleen and brain were measured using flow cytometry.ResultsCD147 expression was rapidly upregulated in the spleen at 4 and 24 h after ischemia onset. The splenic inflammatory response induced by cerebral ischemia was inhibited by αCD147 treatment as demonstrated by the reduced expression of cytokines (TNFα, IL-6, IL-1β) and monocyte chemoattractant protein-1 (MCP-1) in the spleen at 4 and 24 h after ischemia onset. Furthermore, reduced expression of Ly-6C and CCR2 coincided with a decrease in the number of Ly-6ChighMMs subset in the spleen at 4 h after ischemia onset. This suggests αCD147 treatment abrogates cerebral ischemia-induced inflammatory activation of splenic monocytes/macrophages (MMs). In addition, the experiment in splenectomized mice showed the spleen as the major source of infiltrated Ly-6ChighMMs subset in the ischemic brain and that brain infiltration of Ly-6ChighMMs was reduced by αCD147 treatment. These results reveal CD147 as a key mediator of the spleen’s inflammatory activation in response to cerebral ischemia.
Healthcare system indicators associated with modern contraceptive use in Ghana, Kenya, and Nigeria: evidence from the Performance Monitoring and Accountability 2020 data
Authors: Asaolu Ibitola , Nuño Velia Leybas , Ernst Kacey , Taren Douglas , Ehiri John 
Published: October 2019

Abstract

Background
Public health literature is replete with evidence on individual and interpersonal indicators of modern contraceptive use. There is, however, limited knowledge regarding healthcare system indicators of modern contraceptive use. This study assessed how the healthcare system influences use of modern contraceptive among women in Ghana, Kenya, and two large population states in Nigeria.

Methods
This study used data from Phase 1 of the Performance Monitoring and Accountability 2020. The analytical sample was limited to women with a need for contraception, defined as women of reproductive age (15 to 49 years) who wish to delay or limit childbirth. Therefore, this analysis consisted of 1066, 1285, and 1955 women from Nigeria, Ghana, and Kenya respectively. Indicators of healthcare assessed include user-fees, visit by health worker, type of health facility, multiple perinatal services, adolescent reproductive healthcare, density of healthcare workers, and regularity of contraceptive services. All analyses were conducted with SAS (9.4), with statistical significance set at p < 5%.

Results
The prevalence of modern contraceptive was 22.7, 33.2, and 68.9% in Nigeria, Ghana, and Kenya respectively. The odds of modern contraceptive use were higher among Nigerian women who lived within areas that provide adolescent reproductive healthcare (OR = 2.05; 95% C.I. = 1.05—3.99) and Kenyan women residing in locales with polyclinic or hospitals (OR = 1.91; 1.27—2.88). Also, the odds of contraceptive use were higher among Kenyan women who lived in areas with user-fee for contraceptive services (OR = 1.40; 1.07–1.85), but lower among Ghanaian women residing in such areas (OR = 0.46; 0.23—0.92). Lastly, the odds of modern contraceptive use were higher among women visited by a health-worker visit among women in Ghana (OR = 1.63; 1.11—2.42) and Nigeria (OR = 2.97; 1.56—5.67) than those without a visit.

Conclusion
This study found an association between country-specific indicators of healthcare and modern contraceptive use. Evidence from this study can inform policy makers, health workers, and healthcare organizations on specific healthcare factors to target in meeting the need for contraception in Ghana, Kenya, and Nigeria.
Vision does not always help stroke survivors compensate for impaired limb position sense
Authors: Herter Troy M. , Scott Stephen H. , Dukelow Sean P. 
Published: October 2019

Abstract

Background
Position sense is commonly impaired after stroke. Traditional rehabilitation methods instruct patients to visualize their limbs to compensate for impaired position sense.

Objective
Our goal was to evaluate how the use of vision influences impaired position sense.

Methods
We examined 177 stroke survivors, an average of 12.7 days (+/− 10 days (SD)) post-stroke, and 133 neurologically-intact controls with a robotic assessment of position sense. The robot positioned one limb (affected) and subjects attempted to mirror-match the position using the opposite limb (unaffected). Subjects completed the test without, then with vision of their limbs. We examined three measures of position sense: variability (Var), contraction/expansion (C/E) and systematic shift (Shift). We classified stroke survivors as having full compensation if they performed the robotic task abnormally without vision but corrected performance within the range of normal with vision. Stroke survivors were deemed to have partial compensation if they performed the task outside the range of normal without and with vision, but improved significantly with vision. Those with absent compensation performed the task abnormally in both conditions and did not improve with vision.

Results
Many stroke survivors demonstrated impaired position sense with vision occluded [Var: 116 (66%), C/E: 91 (51%), Shift: 52 (29%)]. Of those stroke survivors with impaired position sense, some exhibited full compensation with vision [Var: 23 (20%), C/E: 42 (46%), Shift: 32 (62%)], others showed partial compensation [Var: 37 (32%), C/E: 8 (9%), Shift: 3 (6%)] and many displayed absent compensation (Var: 56 (48%), C/E: 41 (45%), Shift: 17 (33%)]. Stroke survivors with an affected left arm, visuospatial neglect and/or visual field defects were less likely to compensate for impaired position sense using vision.

Conclusions
Our results indicate that vision does not help many stroke survivors compensate for impaired position sense, at least within the current paradigm. This contrasts with historical reports that vision helps compensate for proprioceptive loss following neurologic injuries.
Neural stimulation systems for the control of refractory epilepsy: a review
Authors: Bigelow Matthew D. , Kouzani Abbas Z. 
Published: October 2019

Abstract
Epilepsy affects nearly 1% of the world’s population. A third of epilepsy patients suffer from a kind of epilepsy that cannot be controlled by current medications. For those where surgery is not an option, neurostimulation may be the only alternative to bring relief, improve quality of life, and avoid secondary injury to these patients. Until recently, open loop neurostimulation was the only alternative for these patients. However, for those whose epilepsy is applicable, the medical approval of the responsive neural stimulation and the closed loop vagal nerve stimulation systems have been a step forward in the battle against uncontrolled epilepsy. Nonetheless, improvements can be made to the existing systems and alternative systems can be developed to further improve the quality of life of sufferers of the debilitating condition. In this paper, we first present a brief overview of epilepsy as a disease. Next, we look at the current state of biomarker research in respect to sensing and predicting epileptic seizures. Then, we present the current state of open loop neural stimulation systems. We follow this by investigating the currently approved, and some of the recent experimental, closed loop systems documented in the literature. Finally, we provide discussions on the current state of neural stimulation systems for controlling epilepsy, and directions for future studies.
An efficient and reproducible Agrobacterium-mediated transformation method for hexaploid wheat (Triticum aestivum L.)
Authors: Hayta Sadiye , Smedley Mark A. , Demir Selcen U. , Blundell Robert , Hinchliffe Alison , Atkinson Nicola , Harwood Wendy A. 
Published: October 2019

Abstract

Background
Despite wheat being a worldwide staple, it is still considered the most difficult to transform out of the main cereal crops. Therefore, for the wheat research community, a freely available and effective wheat transformation system is still greatly needed.

Results
We have developed and optimised a reproducible Agrobacterium-mediated transformation system for the spring wheat cv ‘Fielder’ that yields transformation efficiencies of up to 25%. We report on some of the important factors that influence transformation efficiencies. In particular, these include donor plant health, stage of the donor material, pre-treatment by centrifugation, vector type and selection cassette. Transgene copy number data for independent plants regenerated from the same original immature embryo suggests that multiple transgenic events arise from single immature embryos, therefore, actual efficiencies might be even higher than those reported.

Conclusion
We reported here a high-throughput, highly efficient and repeatable transformation system for wheat and this system has been used successfully to introduce genes of interest, for RNAi, over-expression and for CRISPR–Cas9 based genome editing.
Neutral lipid storage disease with myopathy in China: a large multicentric cohort study
Authors: Zhang Wei , Wen Bing , Lu Jun , Zhao Yawen , Hong Daojun , Zhao Zhe , Zhang Cheng , Luo Yuebei , Qi Xueliang , Zhang Yingshuang , Song Xueqin , Zhao Yuying , Zhao Chongbo , Hu Jing , Yang Huan , Wang Zhaoxia , Yan Chuanzhu , Yuan Yun 
Published: October 2019

Abstract

Background
Neutral lipid storage disease with myopathy (NLSDM) is a rare clinical heterogeneous disorder caused by mutations in the patatin-like phospholipase domain-containing 2 (PNPLA2) gene. NLSDM usually presents skeletal myopathy, cardiomyopathy and the multiple organs dysfunction. Around 50 cases of NLSDM have been described worldwide, whereas the comprehensive understanding of this disease are still limited. We therefore recruit NLSDM patients from 10 centers across China, summarize the clinical, muscle imaging, pathological and genetic features, and analyze the genotype-phenotype relationship.

Results
A total of 45 NLSDM patients (18 men and 27 women) were recruited from 40 unrelated families. Thirteen patients were born from consanguineous parents. The phenotypes were classified as asymptomatic hyperCKemia (2/45), pure skeletal myopathy (18/45), pure cardiomyopathy (4/45), and the combination of skeletal myopathy and cardiomyopathy (21/45). Right upper limb weakness was the early and prominent feature in 61.5% of patients. On muscle MRI, the long head of the biceps femoris, semimembranosus and adductor magnus on thighs, the soleus and medial head of the gastrocnemius on lower legs showed the most severe fatty infiltration. Thirty-three families were carrying homozygous mutations, while seven families were carrying compound heterozygous mutations. A total of 23 mutations were identified including 11 (47.8%) point mutations, eight (34.8%) deletions and four (17.4%) insertions. c.757 + 1G > T, c.245G > A and c.187 + 1G > A were the three most frequent mutations. Among four groups of phenotypes, significant differences were shown in disease onset (< 20 years versus ≥20 years old, p = 0.003) and muscle pathology (with rimmed vacuoles versus without rimmed vacuoles, p = 0.001). PNPLA2 mutational type or functional defects did not show great impact on phenotypes.

Conclusion
We outline the clinical and genetic spectrum in a large cohort of NLSDM patients. Selective muscle fatty infiltration on posterior compartment of legs are characteristic of NLSDM. Chinese patients present with distinctive and relative hotspot PNPLA2 mutations. The disease onset age and pathological appearance of rimmed vacuoles are proved to be related with the clinical manifestations. The phenotypes are not strongly influenced by genetic defects, suggesting the multiple environmental risk factors in the development of NLSDM.
A meta-analysis of the relationship between vaginal microecology, human papillomavirus infection and cervical intraepithelial neoplasia
Authors: Liang Yuejuan , Chen Mengjie , Qin Lu , Wan Bing , Wang He 
Published: October 2019

Abstract
Microecology is an emerging discipline in recent years. The female reproductive tract is an important microecological region, and its microecological environment can directly affect women’s cervical health. This meta-analysis aimed to analyze the effects of vaginal microecology on Human papillomavirus (HPV) infection and cervical intraepithelial neoplasia (CIN). PubMed and Web of Science were systematically searched for eligible publications from January 2000 to December 2017. Articles were selected on the basis of specific inclusion and exclusion criteria. The design and quality of all studies were evaluated using the Newcastle-Ottawa Scale (NOS). Odds ratios (ORs) with a 95% confidence interval (95% CI) were calculated. Thirteen eligible studies were selected to evaluate the association of vaginal microecology with HPV infection and CIN. The factors related to HPV infection were bacterial vaginosis (BV) (OR 2.57, 95% CI 1.78–3.71, P<0.05), Candida albicans (VVC) (OR 0.63, 95% CI 0.49–0.82, P < 0.05), Chlamydia trachomatis (CT) (OR 3.16, 95% CI 2.55–3.90, P < 0.05), and Ureaplasma urealyticum (UU) (OR 1.35, 95% CI 1.20–1.51, P < 0.05). BV was also related to CIN (OR 1.56, 95% CI 1.21–2.00, P < 0.05). This meta-analysis of available literature suggested an intimate association of vaginal microecology and HPV infection with CIN. BV, CT and UU were associated to increased HPV infection, VVC was associated to decreased HPV infection, Lactobacillus is not associated to increased HPV infection, BV was associated to increased CIN development risk. Further large-scale studies are needed to confirm our findings.
Prehospital administration of surfactant to a premature neonate in respiratory distress
Authors: Mize Charles Haviland , Dorji Lhab , Zafren Ken 
Published: October 2019

Abstract
The population of the Kingdom of Bhutan is scattered in small villages throughout the eastern Himalaya. Infants born prematurely in villages have no access to neonatal intensive care until they are transported to the national referral hospital, a process that once took hours, if not days. After the introduction of a helicopter critical-care retrieval team, we were able to send a trained team to a remote location that successfully administered surfactant and initiated critical care to a premature, extreme low birth weight infant in severe respiratory distress in the first hour of life. Although the infant was in shock and in a near-arrest state at the time the team arrived, he made an excellent recovery after resuscitation by the team.
Review of malaria situation in Cameroon: technical viewpoint on challenges and prospects for disease elimination
Authors: Antonio-Nkondjio Christophe , Ndo Cyrille , Njiokou Flobert , Bigoga Jude D. , Awono-Ambene Parfait , Etang Josiane , Ekobo Albert Same , Wondji Charles S. 
Published: October 2019

Abstract
Malaria still has a devastating impact on public health and welfare in Cameroon. Despite the increasing number of studies conducted on disease prevalence, transmission patterns or treatment, there are to date, not enough studies summarising findings from previous works in order to identify gaps in knowledge and areas of interest where further evidence is needed to drive malaria elimination efforts. The present study seeks to address these gaps by providing a review of studies conducted so far on malaria in Cameroon since the 1940s to date. Over 250 scientific publications were consulted for this purpose. Although there has been increased scale-up of vector control interventions which significantly reduced the morbidity and mortality to malaria across the country from a prevalence of 41% of the population reporting at least one malaria case episode in 2000 to a prevalence of 24% in 2017, the situation is not yet under control. There is a high variability in disease endemicity between epidemiological settings with prevalence of Plasmodium parasitaemia varying from 7 to 85% in children aged 6 months to 15 years after long-lasting insecticidal nets (LLINs) scale-up. Four species of Plasmodium have been recorded across the country: Plasmodium falciparum, P. malariae, P. ovale and P. vivax. Several primate-infecting Plasmodium spp. are also circulating in Cameroon. A decline of artemisinin-based combinations therapeutic efficacy from 97% in 2006 to 90% in 2016 have been reported. Several mutations in the P. falciparum chloroquine resistance (Pfcrt) and P. falciparum multidrug resistance 1 (Pfmdr1) genes conferring resistance to either 4-amino-quinoleine, mefloquine, halofanthrine and quinine have been documented. Mutations in the Pfdhfr and Pfdhps genes involved in sulfadoxine-pyrimethamine are also on the rise. No mutation associated with artemisinin resistance has been recorded. Sixteen anopheline species contribute to malaria parasite transmission with six recognized as major vectors: An. gambiae, An. coluzzii, An. arabiensis, An. funestus, An. nili and An. moucheti. Studies conducted so far, indicated rapid expansion of DDT, pyrethroid and carbamate resistance in An. gambiae, An. coluzzii, An. arabiensis and An. funestus threatening the performance of LLINs. This review highlights the complex situation of malaria in Cameroon and the need to urgently implement and reinforce integrated control strategies in different epidemiological settings, as part of the substantial efforts to consolidate gains and advance towards malaria elimination in the country.