bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel compound heterozygous pathogenic variants in ASCC1 in a Chinese patient with spinal muscular atrophy with congenital bone fractures 2 : evidence supporting a "Definitive" gene-disease relationship
Authors: Lu Weiliang , Liang Mingxing , Su Jiasun , Wang Jin , Li Lingxiao , Zhang Shujie , Qin Zailong , Huang Limei , Lu Yingchi , Yi Shang , Yi Sheng , Xie BoBo , Zheng Haiyang , Luo Jingsi , Gao Xiaoyan , Shen Yiping 
Published: December 2019

Abstract
Background: A very limited spectrum of ASCC1 pathogenic variants had been reported in five (mostly consanguineous) families with spinal muscular atrophy with congenital bone fractures 2 [OMIM #616867] since 2016. Methods:A proband from a non-consanguineous Chinese family presented with neonatal severe hypotonia, respiratory distress, muscle weakness and atrophy, as well as congenital bone fractures was examined by exome sequencing. Results: A compound heterozygosity of a nonsense (c.932C>G ,p.Ser311Ter) and an exon 5 deletion in ASCC1 segregating with phenotypes was detected, both variants are novel and pathogenic. Since ASCC1 is a relative new disease gene, we performed the gene curation following ClinGen SOP. The existing evidence is sufficient to support a "Definitive" level of disease-gene relationship. Conclusion: This case report expended the mutation spectrum of ASCC1 and support the notion that this novel disease also occur in outbreed populations and this is a rare disease but may still be underdiagnosed due to its perinatal lethal outcomes. Keywords: spinal muscular atrophy with congenital bone fractures 2; ASCC1 ; compound heterozygous; gene curation; exome sequencing
Oxygenation derangements after subarachnoid hemorrhage: incidence and impact on the outcome. Data from a large multicenter, retrospective study.
Authors: Mazeraud Aurelien , Robba Chiara , Iaquaniello Carolina , Rebora Paola , Vargiolu Alessia , Rass Verena , Bogossian Elisa , Helbok Reimund , Taccone Fabio , Citerio Giuseppe 
Published: December 2019

Abstract
BackgroundHypoxemia and hyperoxemia are frequent after acute subarachnoid hemorrhage (aSAH) and are associated with an increase in morbidity and mortality. Among the pulmonary complications causing oxygen derangements, acute respiratory distress syndrome (ARDS) seems to be crucial, with a reported incidence ranging from 11 to 50%. MethodsWe designed a multicentric, retrospective cohort study in tree intensive care in Europe. We collected data between January 2009 and December 2017. We included adult patients (≥18 years) with a diagnosis of aSAH. Hypoxemia was defined as PaO2 <60mmHg, mild hyperoxemia as PaO2>120mmHg, and severe hyperoxemia as PaO2>200mmHg. The primary aim of this study was to assess the incidence of episodes of hypoxemia, hyperoxemia, and the oxygen variability values (calculated as the daily difference between the highest and the lowest arterial partial pressure of oxygen (PaO2)) during the first week after the intensive care unit (ICU) admission. Secondary aims included the evaluation of the incidence of ARDS according to the Berlin criteria, and the assessment of the effect of oxygen derangements on patients’ outcomes.Results855 patients fulfilled the inclusion criteria. 6.4% of the patients presented at least one episode of hypoxemia (PaO2 <60mmHg), 56.6% of mild hyperoxemia (PaO2 >120mmHg), and 16.8% of severe hyperoxemia (PaO2 >200mmHg). The cumulative incidence of ARDS resulted in 2.2% on the first day since ICU admission, 3.2% by three days, and 3.6% by seven days. A lower Glasgow Coma Scale score (GCS) at admission, longer duration of mechanical ventilation, higher PaO2 variability, hypoxemia, and ARDS occurrence were independently associated with poor outcome.ConclusionsHypoxemia and hyperoxemia episodes are frequent in the first 7-days of ICU stay after aSAH, whereas ARDS has a low incidence. The severity of aSAH but also ARDS occurrence, oxygenation parameters, and duration of MV are associated with patients’ outcomes
Impact of indoor residual spraying on malaria transmission in the Moïssala health district, Chad
Authors: Israël Demba Kodindo , Abel Diomba Dobar , Oumar Adoum Mahamat , Tchonfinet Moundai , Fadel Amen Nakebang , Elise Yangalbé-Kalnoné , Abba Brahim Adef , Belemel Djédion , Pallay Mallaye , Clément Kerah-Hinzoumbe 
Published: December 2019

Abstract
BackgroudMalaria is a major public health and development problem in Africa. In Chad in 2016, with 720 765 confirmed cases and 1 686 deaths, malaria is the main cause of consultations, hospitalizations and deaths in health facilities. A longitudinal entomological study was carried out from 07 to 24 December 2016 in the Moïssala health district. The objective of the study was to assess the impact of malaria transmission one year after two cycles of indoor residual spraying of 80% bendiocarb wettable powder (Ficam WP 80 W).MethodsTwo areas were defined for the study: the town of Dembo, located in the sprayed area, was chosen as the test town and Moïssala, located in the untreated area, was chosen as the control town. Two sampling methods were used: collection of resting endophilic fauna and direct capture of aggressive mosquitoes from human subjects. ResultsA total of 16 sessions of catches on human subjects totalling 32 man-nights were conducted and 160 rooms were sprayed per site. For 160 sprayed chambers per site, two anopheles were captured in Dembo compared to 547 in Moïssala. Three anophelian species have been morphologically identified. In Moïssala, An gambiae sl (An colluzzii : 96%, An gambiae : 4%), An funestus and An rufipes were captured at rest in the rooms and on human bait. In Dembo, the two anopheles, An colluzzii and An funestus were captured at rest in the rooms. On human bait as in endophilic fauna, An gambiae sp was the most common species in Moïssala. The aggressive anophelian density was zero in Dembo while it is 9 bites per man per night in Mosesala. Only Anopheles gambiae sp was found infected in aggressive wildlife. The sporozoite index of the aggressive fauna of An gambiae sp was 7.45%. Malaria transmission was estimated at 0.67 infected bites per man per night, or 244.55 infected bites per man per year. In endophilic fauna, An gambiae sp and An rufipes were the two species found infected in Moïssala with sporozoite indices of 6.70% (23/343) and 20% (2/10) respectively. However, in Dembo, neither of the two captured individuals was found infected.ConclusionsThe indoor residual spraying campaign in the eastern zone of the Moïssala health district has led to the collapse of the density and aggressiveness of malaria vectors. However, its evaluation over a short period of time is not sufficient to assess the impact of malaria transmission in this stable and highly endemic malaria zone.
Evolution of Plasmodium vivax populations in border areas of the Greater Mekong Subregion during malaria elimination
Authors: Li Yuling , Hu Yubing , Zhao Yan , Wang Qinghui , Mbenda Huguette Gaelle Ngassa , Kittichai Veerayuth , Lawpoolsri Saranath , Sattabongkot Jetsumon , Menezes Lynette , Liu Xiaoming , Cui Liwang , Cao Yaming 
Published: December 2019

Abstract
BackgroundCountries within the Greater Mekong Subregion (GMS) of Southeast Asia have committed to eliminating malaria by 2030. Although malaria situation has greatly improved, Plasmodium vivax remains at international border regions. Therefore, to gain a better understanding of transmission dynamics, knowledge on the evolution of P. vivax populations after the scale-up of control interventions will guide more effective targeted control efforts. MethodsWe investigated genetic diversity and population structures in 206 longitudinally collected P. vivax clinical samples in two international border areas at the China-Myanmar border (CMB, n=50 in 2004 and n=52 in 2016) and western Thailand border (n=50 in 2012 and n=54 in 2015). Parasites were genotyped using 10 microsatellite markers. ResultsDespite intensified control efforts, genetic diversity in the four populations remained high (HE = 0.66-0.86). The proportions of polyclonal infections showed substantial decreases to 23.7 and 30.7% in the CMB and western Thailand, respectively, with corresponding decreases in the multiplicity of infection. Consistent with the shrinking map of malaria transmission in the GMS over time, there were also increases in multilocus linkage disequilibrium, suggesting of more fragmented and increasingly inbred parasite populations. There were considerable genetic differentiation and subdivision with the four tested populations. Various degrees of clustering were evident between the older parasite samples collected in 2004 at the CMB with the 2016 CMB and 2012 Thailand populations, suggesting some of these parasites had shared ancestry. In contrast, the 2015 Thailand population was genetically distinctive, which may reflect a process of population replacement. The moderately large effective population sizes and proportions of polyclonal infections highlight the necessity of further coordinated and integrated control efforts on both sides of the borders in the pursuit of malaria elimination. ConclusionsWith enhanced control efforts on malaria elimination, P. vivax population in the GMS has fragmented into a limited number of clustered foci, but the presence of large P. vivax reservoirs still sustains genetic diversity and transmission. These findings provide new insights into P. vivax transmission dynamics and population structure in this area.
Correlation of tumor necrosis factor-α -308G&gt;A polymorphism with susceptibility, clinical manifestations and severity in Behçet syndrome: evidences from an Italian genetic case-control study
Authors: Padula Maria Carmela , Leccese Pietro , Lascaro Nancy , Radice Rosa Paola , Limongi Antonina Rita , Sorrento Giusi Gaia , Carbone Teresa , Padula Angela Anna , Martelli Giuseppe , D’Angelo Salvatore 
Published: December 2019

Abstract
Background The tumor necrosis factor (TNF)α is a multifunctional proinflammatory cytokine, implicated in a variety of diseases, including Behçet syndrome (BS), a rare vasculitis with a wide spectrum of clinical manifestations. The aim of the present study was to investigate the association between a functional drug-response TNFα gene polymorphism (at the positions of -308; rs1800629) and both disease susceptibility and clinical manifestations in a cohort of Italian BS patients compared with healthy controls (HC).Methods We recruited 130 Italian patients with BS consecutively seen at Rheumatology Institute of Lucania (Italy) and 100 ethnically, age and gender matched HC. Demographic and clinical features were retrieved by medical records. Specific primer pairs were designed for TNFα coverage. Genomic DNA isolation, primer-specific PCR amplification and direct sequencing were performed for genotyping our group of patients and controls. In silico analysis was downstream performed using Mutation Surveyor software (SoftGenetics, USA) and NCBI-BlastN on line tool for the query-subject similarity analysis.Results The genotype distribution of BS patients and HC underlined a higher percentage of wild-type GG genotype in BS patients group vs HC (106/130 patients, 81.5% vs 91/100 HC, 91%; p<0.05), while the heterozygous genotype (GA) was identified in 24/130 patients (18.5%) vs 9/100 HC (9%) (p<0.05). GA genotype was significantly associated with the disease (OR=2.29, 95% CI 1.01-5.18). No significant association was recognized between the SNP and the BS clinical manifestations, as well as with disease severity (Krause's index).Conclusions We found statistically significant higher frequency of TNFα rs1800629 GA genotype in patients than in controls. No significant association was recognized between the polymorphism and the clinical parameters, as well as between the SNP and the disease severity. Our data need to be confirmed in larger cohort of patients and matched controls.
Tussilagone Inhibits Osteoclastogenesis and Periprosthetic Osteolysis by Suppressing the NF-κb and p38 MAPK Signaling Pathways
Authors: Hu Xuantao , Ouyang Zhengxiao , Peng Dan , Yin Ziqing , Chen Xia , Jiang Guangyao , Yang Daishui , Cao Ziqin , Li Shuai , Liu Zicheng 
Published: December 2019

Abstract
Backgroud: Aseptic prosthetic loosening is one of main factor producing poor prognosis of limb function after joint replacement and requiring troublesome revision surgery. It is featured by wear particle–induced periprosthetic osteolysis mediated by excessive osteoclasts activated in inflammatory cell context. In our previous study, some natural compounds showing anti-osteoclast trait with high cost-efficiency and few side effects. Tussilagone (TUS), as the main functional extract from Tussilago Farfara precedently used for relieving cough, asthma and eliminating phlegm in traditional medicine, has been proved to appease several RAW264.7-mediated inflammatory diseases via suppressing osteoclast-related signaling cascades. However, whether and how TUS can improve aseptic prosthetic loosening via modulating osteoclast-mediated bone resorption still need to be answered. Methods: We established a murine calvarial osteolysis model to detect the preventative effect of TUS on osteolysis in vivo. Micro-CT scanning and histomorphometric analysis were used to determine the variation of bone resorption and osteoclastogenesis in samples. The anti-osteoclast-differentiation and anti-bone-resorption bioactivities of TUS in vitro were investigated using bone slice resorption pit evaluation and interference caused by cytotoxicity of TUS was excluded according to CCK-8 assay. Quantitative PCR analysis was applied to prove the decreased expression of osteoclast-specific genes after TUS treatment. The inhibition effect of TUS on NF-κb and p38 MAPK signaling pathways was testified by western blotting and NF-κB-linked luciferase reporter gene assay.Results: TUS demonstrated bone protective effect against osteolysis in murine calvarial osteolysis model with reduced osteoclasts compared to the control group. Following studies in vitro witnessed that TUS exert anti-osteoclastogenesis and anti-bone-resorption effects in both BMMs and RAW264.7 cells, as evidenced by the decline of osteoclast specific genes according to quantative PCR. Western blotting revealed that TUS-treated demonstrated inhibited IκBα degradation and p38 phosphorylation.Conclusions: Collectively, for the first time our studies prove that TUS inhibits osteoclastogenesis by suppressing the NF-κb and p38 MAPK signaling pathways, therefore serving as a potential natural compound to treat periprosthetic osteolysis-induced aseptic prosthetic loosening.
Characterization of Ethanol Producing Yeasts for Their Efficiency in Ethanol production, Salt Tolerance, and Utilization of Glucose and Xylose.
Authors: Joshi Jarina , Bhattarai Tribikram , Yadav Amar , Sreer Lakshmaiah 
Published: December 2019

Abstract
Yeast are the mainstay in ethanol production industry. Search for efficient yeast strains that are salt tolerant and utilize both hexoses (glucose) and pentoses (xylose and arabinose) is important in fermentation industry. In this regard,12 yeast strains, viz., CDBT1-12, were isolated from various sources and characterized. Molecular characterization of the yeast strains was done by sequencing 26S rRNA gene, D1D2 region. Out of 12 isolates, 10 were found to be Saccharomyces cerevisiae , CDBT7 was Wikerhamomyces anomalous , and CDBT8 was Cyberlindnera fabianii . The yeast isolates were characterized in terms of their ethanol production efficiency, salt tolerance and ability to utilize of glucose and xylose. All the strains were found to be good ethanol producers. Yeast strain CDBT2 was found to have tolerance for high salt (up to 15%) and ethanol (up to 16%) concentrations. Yeast strain CDBT7 was found to utilize both glucose and xylose without compromising on ethanol production efficiency. The CDBT7 strain was also salt tolerant (up to15%).Yeast strain CDBT2 when grown in an electrochemical cell with low levels of applied external voltage, alcohol dehydrogenase (ADH1) and pyruvate decarboxylase (PDC1) mRNA levels were increased by 2.78 ± 0.80 and 1.12 ± 0.37 fold, respectively. We believe, the latter observation is novel and it has not been reported previously. It also further supports our previous observation of increase in level of alcohol production by CDBT2 strain in the presence of applied electrical current.
Human disease-related pathways increasing with opportunistic pathogens bloom in intestinal microbiome after vancomycin exposure and restoration with fecal transplantation by simulator of the human intestinal microbial ecosystem (SHIME)
Authors: Liu Lei , Wang Qing , Qi Hongmei , Das Ranjit , Lin Huai , Shi Jingliang , Wang Siyi , Yang Jing , Xue Yingang , Mao Daqing , Luo Yi 
Published: December 2019

Abstract
Background: Antibiotics are growing reported to cause human intestinal microbial disorders with increasing abundances of opportunistic pathogens, and fecal microbiota transplantation (FMT) has been confirmed to restore the dysbiosis of gut flora in many kinds of intestinal disease. However, to date, few studies have focused on the bloomed opportunistic pathogens associated human disease-related pathways as well as antibiotic resistance genes (ARGs) after vancomycin exposure, and there is limited information on using FMT for restoration of intestinal microbiome affected by antibiotics. Methods: This study investigated effects of vancomycin on the opportunistic pathogens, human disease-related pathways as well as ARGs in human gut, and the restoration of intestinal microbiome by FMT. Using the simulator of the human intestinal microbial ecosystem (SHIME), two reactors (representing the ascending and descending colon, respectively) were inoculated with human intestinal microbiota from a healthy adult volunteer who did not suffer from gastrointestinal diseases or take any antibiotic in the previous six months. Samples were collected from the reactors at six-time points (before treatment, after seven days of individual 10 mg/L, 100 mg/L, 1000 mg/L vancomycin treatment, 14 days following the termination of vancomycin and 14 days following FMT). The intestinal microbiome composition and function were analyzed using 16S rRNA gene sequencing and High-throughput Quantitative PCR (HT-qPCR).Results: Vancomycin treatment substantially increased human disease-related pathways and decreased abundances of ARGs. Besides, the bloomed opportunistic pathogens including Achromobacter, Klebsiella, and Pseudomonas, caused by vancomycin exposure, were positively correlated with human disease-related pathways. The microbiota abundance and genes of human disease-related pathways and antibiotic resistance showed a remarkable return towards baseline after FMT, but not for natural recovery. Conclusions: These findings suggest that impacts of vancomycin on human gut are profound and FMT will be a promising strategy in clinical application that can restore the dysbiosis of gut microbiota, which may be valuable for directing future work.
TÜRK HUKUKUNDA YERİNE GETİRİLMİŞ BAĞIŞLAMANIN GERİ ALINMASI VE BGB. 313. ÇERÇEVESİNDE ALMAN FEDERAL YÜKSEK MAHKEME KARARININ DÜŞÜNDÜRDÜKLERİ
Authors: YILMAZ Çiğdem Mine 
Published: December 2019

Bağışlama sözleşmesinin, sözleşme
taraflarından sadece bağışlayana borç yükleyen bir sözleşme olması sebebiyle
6098 sayılı Türk Borçlar Kanunu’muzda, bağışlayanı ve onun malvarlığını
korumaya yönelik düzenlemeler öngörülmüştür . Bu sözleşme ile bağışlanan, yani
kendisine değer kazandırılan kişinin zenginleştirilmesi amacı güdülmektedir.
Çalışmada, Türk hukukunda yapılan bağışlamanın geri istenebilmesi için
bağışlamaya özgü sebepler ve bağışlama dışında hangi hukuki kurumlara
başvurulabileceği Alman Medeni Kanunu, Burgerliches Gesetzbuch’da (BGB) yer
alan “işlem münasebeti esası”nın felsefesine de değinilerek açıklanmaya ve
önerilerde bulunulmaya çalışılacaktır. Alman Federal Yüksek Mahkemesi,
Bundesgerichtshof’un, (BGH) yerleşik içtihat hukuku uyarınca, evliliğe ilişkin
bağışlama durumu, eşlerden birinin diğerine bir mal varlığını evlilikten dolayı
ve evlilikle hayat birliğinin gerçekleştirilmesi ve oluşturulması, muhafaza
edilmesi veya güvence altına alınması maksadıyla vermesi, bununla evlilik yaşam
birliğinin var olmasını ve bu birliktelik dâhilinde verdiği bu mal varlığından
ve onun getirilerinden istifade etmeye devam etme düşüncesi veya beklentisi
içinde olmasıyla mevcut olur. Bağışlamanın, münasebet esası burada yatmaktadır.
Ne var ki, eşlerin yasal mal rejimi çerçevesinde, evlilikten dolayı bağışlama
halleri durumu mevcutsa iade işlemlerinin - bir mal ayrılığı rejiminin mevcut
olmasından farklı olarak – BGB. Art. 313
uyarınca halledilmesi bir istisnadır. Federal Mahkemeye göre, kazanç
denkleştirmesi gerçekleştirilir ve yalnızca bunun uygun olmayan bir sonuca yol
açması durumunda BGB. Art. 313. uyarınca bir iade işlemi düşünülebilir.
Boundary condition identification of a clamped honeycomb sandwich panel based on thin-layer element
Authors: Xu Yu , Cao Zhifu , Jiang Dong 
Published: December 2019

The stiffness of boundary conditions in mechanical structures is difficult to represent. An approach on high fidelity modeling of the clamped boundary condition is proposed in this paper. Firstly, the normal and tangential stiffness of the contact surface of the clamped boundary condition is parameterized by using thin-layer element with isotropic material. Secondly, the material parameter is identified by minimizing the discrepancy between the calculated results and the experimental data, and parameter identification can be treated as an optimization problem. Experimental investigation is undertaken to verify the proposed method by employing an aluminum honeycomb panel, the numerical model of which is constructed by using the equivalent theory. Thin-layer elements with different properties are used to simulate the mechanical properties in different area of the boundary conditions, and the experimental modal data is adopted to identify the material parameters. Results show that the weighted matrix is a crucial option in the parameter identification procedure, and the width to thickness ratio of the thin layer element has a great influence on the identification results. After parameter identification, the error of the first three order of the modal frequencies is less than 2.7 %, the thin-layer element can accurately reflect the mechanical performance of clamped boundary condition.