bluuebunny/crossref_metadata_2025 huggingface dataset:
NEUROCUTANEOUS SYNDROMES: EVALUATION OF CLINICAL AND NEURORADIOLOGICAL FINDINGS
Authors: Çavuşoğlu Dilek , Özer Gökaslan Çiğdem
Published: January 2021

OBJECTIVE: Neurofibromatosis type I (NF1), Tuberous sclerosis complex (TSC) and Sturge-Weber syndrome (SWS) are the most common neurocutaneous syndromes. The purpose of this study is to evaluate the clinical and neuroradiological manifestations of patients diagnosed with NF1, TSC, and SWS.MATERIAL AND METHODS: In our clinic, records of 15 patients with NF1, TSC, and SWS were retrospectively reviewed between December 2017 and May 2019. Clinical and neuroradiological manifestations of patients were detailed.RESULTS: 15 patients consisting of 9 NF1, 5 TSC, and 1 SWS were determined between the ages of 9 days and 13,83 years (5 females and 10 males). All NF1 patients had café-au-lait spots. One (11.1%) with lisch nodules, one (11.1%) with optic glioma, one (11.1%) with epilepsy, two (22.2%) with macrocephaly, two (22.2%) with hydrocephalus, one (11.1%) with optic glioma and seven (77.7%) with family history were established. All TSC patients had hypomelanotic macules and epilepsy. It was indicated cardiac rhabdomyoma in 3 (60%) patients, angiomyolipoma in one (20%) patient and polycystic kidney in one (20%) patient. The patient with SWS was showed available of facial angioma, glaucoma, and epilepsy. It was pointed UBOs (unknown bright objects) with 6 (66.6%) patients, 2 (22.2%) patients with hydrocephalus, one (11.1%) patient with subependymal nodule and one (11.1%) patient with optic glioma in NF1 patients. Brain magnetic resonance imaging of all TSC patients showed cortical/subcortical tubers and two patients with subependymal nodules. Cortical and parenchymal atrophy and calcification were presented in cranial computed tomography of the patient with SWS.CONCLUSIONS: Clinical and neuroradiological manifestations of neurocutaneous syndrome are guidance for diagnosis so that detailed examination and neuroradiological perspective on neurocutaneous diseases will provide convenience in diagnosis and follow-up.
Wirusy onkogenne a nowotwory
Authors: Warowicka Alicja , Nawrot Robert , Broniarczyk Justyna , Węglewska Martyna , Goździcka-Józefiak Anna
Published: January 2021

Wirusy onkogenne (onkowirusy) są zaangażowane w powstawanie około 12% nowotworów u ludzi. Obecnie wirusy, o których wiadomo, że powodują raka, to wirusy zapalenia wątroby typu C i B (HCV i HBV), wirusy brodawczaka ludzkiego (HPV), wirus polyoma komórek Merkla (MCV), ludzki herpeswirus-8 (HHV-8) i ludzki wirus limfotropowy komórek T (HTLV-1). Wirusy nie są jednak pełnymi kancerogenami i w procesie transformacji nowotworowej odgrywają różną rolę. Onkowirusy mogą bezpośrednio zakłócać funkcjonowanie genów kodujących komórkowe białka regulatorowe w wyniku insercji własnego genomu do genomu komórkowego. Mają także własne geny kodujące białka, które zaburzają regulację procesów komórkowych lub zawierają onkogeny wirusowe v-onc, które mogą brać udział bezpośrednio w rozwoju procesu nowotworowego.
GREEN MARKETING TOOLS EFFECT ON CONSUMER BUYING DECISION IN THE BOTTLED WATER INDUSTRY
Authors: Prihandono Dorojatun , Wijaya Angga Pandu , Rizqiana Ina , Yahya Wan Kalthom , Prabumenang Agung Kresnamurti Rivai
Published: January 2021

Purpose of the study: This study aims to examine green marketing tools, eco-friendly labels, and green advertising influence on consumer purchase behavior in mineral water. This research elaborates on the Ades brand, which promotes eco-friendly image in Indonesia. Green marketing has become a trending issue in all consumer package goods industries in the past decades. The bottled water industry faces enormous challenges to produce an idiosyncratic product to win a highly competitive market.

Methodology: This study applies the partial least square analysis to examine the variable relationships. 115 respondents were involved in this study. Data collected using a questionnaire and processed by SmartPLS 3.0.

Main Findings: The analysis results show that eco-friendly Label and green advertising have a positive and significant relationship on the consumer purchase decision.

Applications of this study: The results provide valuable inputs for bottled water manufacturers to commence a green marketing campaign that fits regional and global markets to improve sales performance and overcome challenges.

Novelty/Originality of this study: Previous studies are rarely concern on consumer behavior in purchasing bottled water, therefore this research attempt to elaborate better understanding using the theory of planned behavior.
Die Routiniertheit des Sprachgebrauchs am Beispiel kollokativer Verbindungen
Authors: Księżyk Felicja
Published: January 2021

Die sprachliche Kommunikation beruht stärker als bisher angenommen auf einem routinemäßigen Sprachgebrauch. Als typisches Beispiel für wiederkehrende Formulierungen lassen sich Kollokationen anführen. Einerseits handelt es sich hierbei um Wortkombinationen, die durch die außersprachliche Realität bedingt sind, die andererseits aber auch einzelsprachspezifisch, konventionell sein können und Erscheinungen der Sprachnorm darstellen. Im vorliegenden Beitrag werden die wesentlichen Merkmale von Kollokationen diskutiert, und zwar in Bezug auf das Sprachenpaar Deutsch-Polnisch.
LEGAL REGULATIONS FOR THE GENERAL ELECTION SYSTEM IN INDONESIA FROM THE 1955 ELECTION TO THE CONCURRENT ELECTION OF 2019
Authors: Rannie Mahesa
Published: January 2021

Throughout its history, Indonesia has held general elections many times from 1955 to 2019. During that long period of time, Indonesia implemented a different electoral system at each election. The arrangement of the electoral system in Indonesia always changes from time to time in each election administration. In the process of changing the laws and the regulations for every election, there has always been legal political dynamics. After the 2014 elections, there have been changes regarding the conduct of elections in Indonesia. The Constitutional Court (MK) granted the petition for a judicial review of Law Number 42 of 2008 concerning the Election of President and Vice President in 2014, so that the implementation of elections in Indonesia entered a new phase in 2019 and beyond. In 2019, for the first time Indonesia held simultaneous elections. The methodology used in this study is normative. The approaches used in this study are the historical approach, the statute approach, the legal analysis approach, and the conceptual approach. Legal arrangements regarding the conduct of elections always change, starting from the highest level of legislative regulations to the lowest (from the laws to the General Election Commission regulations, presidential decrees, ministerial regulations, or other regulations). The changes in the regulations regarding the implementation of elections in Indonesia have been present since the time of the 1955 elections until the 2019 elections. Since the implementation of the 1955 elections, Indonesia has always practiced a proportional electoral system, the electoral system that is considered suitable to be applied in Indonesia. This proportional electoral system is practiced with various modifications (both the open proportional electoral system and the closed proportional system). There are even district elements in the proportional electoral system in Indonesia, for example there are electoral districts that can be equated with districts in the district electoral system. The practice of the electoral system to be used in the elections in Indonesia is almost always subject to debate, both among constitutional law intellectuals and politics.
On Some Damped 2 Body Problems
Authors: Haraux Alain
Published: January 2021

The usual equation for both motions of a single planet around the sun and electrons in the deterministic Rutherford-Bohr atomic model is conservative with a singular potential at the origin. When a dissipation is added, new phenomena appear which were investigated thoroughly by R. Ortega and his co-authors between 2014 and 2017, in particular all solutions are bounded and tend to $0$ for $t$ large, some of them with asymptotically spiraling exponentially fast convergence to the center. We provide explicit estimates for the bounds in the general case that we refine under specific restrictions on the initial state, and we give a formal calculation which could be used to determine practically some special asymptotically spiraling orbits. Besides, a related model with exponentially damped central charge or mass gives some explicit exponentially decaying solutions which might help future investigations. An atomic contraction hypothesis related to the asymptotic dying off of solutions proven for the dissipative model might give a solution to some intriguing phenomena observed in paleontology, familiar electrical devices and high scale cosmology
Online Pressrooms: Journalists’ Expectations from Public Relations Practitioners Concerning Online Media Relations
Authors: Atabek Umit , Alikilic Ozlem Asman
Published: January 2021

Online pressrooms are important for public relations practitioners when improving their media relations in a rapidly developing new media ecosystem. This paper aims to provide an insight into the journalists’ preferences when retrieving information from online pressrooms. In a mixed design, qualitative and quantitative data were collected from Turkish journalists. As the first step of the study, a focus group with 11 journalists was conducted to understand what the expectations of journalists of online pressrooms are, and how they verbally express these demands. These qualitative data were then used for the structuring of a survey questionnaire that was applied to a sample of 155 journalists. Results indicate that journalists were frustrated by the current state of online pressrooms. Journalists asserted that information-rich and skilfully designed pressrooms help increase the corporations’ credibility. Journalists designated visuals and news archives as the most important contents for an online pressroom. It is also found that journalists trust more an organization if they receive fast answers from an authorized media relations person. Furthermore, our cluster analysis revealed that junior journalists with more new media practice have more trust in organizations with successful online media relations.
Book review of Demența digitală. Cum ne tulburã mintea noile tehnologii [Digitale Demenz. Wie wir uns und unsere Kinder um den Verstand bringen]
Authors: Răducu Roberta
Published: January 2021

Every technological advancement that facilitates communication and the spread of information (motion pictures, radio, television, computers, smartphones and Internet) has been greeted by the public as the new way to improve diverse fields, including the educational system. Manfred Spitzer, neurosciences expert, specialized on studying the learning processes points out in the book Digital Dementia that a fashionable information and communication technological discovery is not necessarily compatible with educating the minds of the youngest.
Relação da intensidade e direção do vento com a maré meteorológica
Authors: Vedana Jaísa , Paiotti do Canto Marina , Schvambach Amabilly
Published: January 2021

O cotidiano da população é influenciado por diversos fenômenos, um deles, chamado maré, que consiste na variação do nível das massas de água que circundam os continentes. Define-se como maré meteorológica a diferença entre a maré observada e a maré astronômica são provocadas por duas causas: variação de pressão atmosférica e troca de momentum ar-mar. Durante este fenômeno ocorre o empilhamento da massa d’água junto à costa, podendo ultrapassar o seu limite natural, alcançando áreas ocupadas e edificadas causando impactos negativos. Deste modo, a identificação de um padrão de associação de direção e intensidade de ventos, associado a eventos de maré meteorológica, auxilia à tomada de decisão do poder público, no que se refere à gestão costeira, focada na precaução. A presente pesquisa teve como objetivo determinar os valores da maré meteorológica e a relação desta com a intensidade e direção dos ventos incidentes no período de 2014 a 2019 no município de Itapoá/SC. Puderam-se observar ventos de maiores intensidades entre os meses de janeiro a março e em agosto e setembro, menores intensidades entre os meses de abril a julho. Os dados mostraram que existe baixa correlação positiva entre a maré meteorológica e as componentes meridional e zonal do vento, porém a mais significativa é a componente meridional. A análise dos dados e a revisão bibliográfica indicam que há alguma relação entre as forçantes atmosféricas (intensidade e direção do vento) e os eventos de maré meteorológica.
Does Computed Tomography of Kidney, Ureter and Bladder (CTKUB) Affect The Management of Patients with Suspected Renal Colic in Emergency Department?
Authors: Chaudhry Mehmood , Buhumaid Rasha , Banimatar Khulood A Al Haj , Zaabi Ruqya Al , Ramahi Ismail Al , Chaudhry Rayhan
Published: January 2021

Introduction CTKUB use in patients presenting to Emergency Department (ED) with suspected renal colic has increased by 10-fold over last few years. However, its impact on the urological intervention is not fully known.Methods We performed a retrospective study of adult patients, presenting consecutively to ED with suspected renal colic who underwent CTKUB from January to June 2014. We calculated descriptive summary statistics for analysis to determine the association of predefined radiological and patients’ characteristics on the urological intervention.Results Of the 282 patients enrolled in the study, 38% had stones. Commonest locations of stone were ureter (15%), uretero-vesical junction (12.4%). Of the study participants, 2% of the patients underwent urological intervention. Chi Square analysis did not find any significant associations between radiological or patients related characteristics and urological interventionConclusion There was no significant correlation between CTKUB findings or patients’ characteristics and urological intervention in this study cohort.
Infrared Small Target Tracking Based on Target Spatial Distribution With Improved Kernelized Correlation Filtering
Authors: Kou ZhiQiang , Hamdulla Askar
Published: January 2021

The application of correlation filtering in infrared small target tracking has been a mature research field. Traditionalcorrelation filtering is to describe the target features by using a single feature, which can not solve the problem of target occlusion. Because of the fast moving speed and lack of re-detection mechanism, the target tracking will produce offset, which leads to the performance of the tracker to decline. In view of the above problems, a new multi feature re detection framework is proposed for long-term tracking of small targets. The feature selects multi feature weighting function, considers the importance of intensity feature to infrared target and different regions, calculates the gray distribution weighting function of the target, and combines the weighting function into the correlation filter. Before updating the template, to verify the reliability of target detection, the average peak correlation energy is used as the confidence of candidate region. When the target is completely occluded, the prediction result of Kalman filter is used as the optimal estimation of target position in the next frame. A large number of experimental results on different video sequences show that the tracking accuracy of this method is greatly improved compared with the baseline method.
Changes over time in HIV testing and counselling uptake and associated factors among youth in Zambia: A cross-sectional analysis of Demographic and Health Surveys from 2007 to 2018
Authors: Heri Aimé , Cavallaro Francesca , Ahmed Nurilign , Musheke Maurice , Matsui Mitsuaki
Published: January 2021

IntroductionZambia is among the countries with the highest HIV burden and where youth remain disproportionally affected. Access to HIV testing and counselling (HTC) is a crucial step to ensure the reduction of HIV transmission. This study examines the changes that occurred between 2007 and 2018 in access to HTC, inequities in testing uptake, and determinants of HTC uptake among youth.MethodsWe carried out repeated cross-sectional analyses using three Zambian Demographic and Health Surveys (2007, 2013-14, and 2018). We calculated the percentage of women and men ages 15-24 years old who were tested for HIV in the last 12 months. We analysed inequity in HTC coverage using indicators of absolute inequality. We performed bivariate and multivariate logistic regression analyses to identify predictors of HTC uptake in the last 12 months.ResultsHIV testing uptake increased between 2007 and 2018, from 45% to 92% among pregnant women, 10% to 58% among non-pregnant women, and from 10% to 49% among men. By 2018 roughly 60% of youth tested in the past 12 months used a government health centre. Mobile clinics were the second most common source reaching up to 32% among adolescent boys by 2018. Multivariate analysis conducted among men and non-pregnant women showed higher odds of testing among 20-24 year-olds than adolescents (aOR=1.55, [95%CI:1.30-1.84], among men; and aOR=1.74, [1.40-2.15] among women). Among men, being circumcised (aOR=1.57, [1.32-1.88]) and in a union (aOR=2.44, [1.83-3.25]) were associated with increased odds of testing. For women greater odds of testing were associated with higher levels of education (aOR=6.97, [2.82-17.19]) and not reporting HIV-related stigma. Education-based inequity was considerably widened among women than men by 2018.ConclusionHTC uptake among Zambian youth improved considerably by 2018 and reached 65% and 49% tested in the last 12 months for women and men, respectively. However, achieving the goal of 90% envisioned by 2020 will require sustaining the success gained through government health centres, and scaling up community-led approaches proven acceptable and effective in reaching young men and adolescent girls who are less easy to reach through the government facilities.
Safety and Efficacy of Secondary Mandibular Reconstruction Using a Free Osteo-cutaneous Fibula Flap after Segmental Mandibular Resection: A Retrospective Case Control Study
Authors: Yamakawa Sho , Hayashida Kenji
Published: January 2021

Background: Free osteocutaneous fibula flap (FFF) is currently considered the best option for segmental mandibular reconstruction; however, there are no reports comparing secondary with primary reconstructions using FFF. This study aimed to evaluate the safety and efficacy of secondary mandibular reconstruction using FFF when compared with primary mandibular reconstruction. Methods: From October 2018 to February 2020, patients who underwent mandibular reconstruction using FFF after segmental mandibulectomy were retrospectively reviewed. The size and location of the mandibular defect, the segment length and number of osteotomies in the fibula, types of the mandibular plating system, and laterality of the recipient vessels were recorded from the surgical notes. Flap survival, duration of nasogastric tube use, and implant installation after reconstruction were recorded as indices of postoperative evaluation. Results: Twelve patients underwent mandibular reconstruction using FFF during the study period. There were no significant differences in demographic characteristics other than body mass index between the primary (n=8) and secondary (n=4) reconstruction groups. No significant differences were observed in the size and location of defects, the segment length and number of osteotomies in the fibula, and the types of mandibular plating system. The laterality of recipient vessels was ipsilateral in all cases of primary reconstructions and contralateral in all cases of secondary reconstructions. Three out of eight patients with primary FFF reconstruction developed partial flap necrosis. Four patients in the secondary FFF reconstruction group achieved complete flap survival. The duration of use of the nasogastric tube and implant installation after reconstruction was comparable between the two groups. Conclusion: This clinical case study demonstrates the safety and efficacy of secondary mandibular reconstructions using FFF.
Hydrologic soil group based curve number matrix modeling for Enset-Based land use system in Meki River Watershed, Western Lake Ziway Sub-Basin, Central Rift Valley of Ethiopia
Authors: Woldesenbet Alemu Beyene , Wudmatas Sebsebe Demisew , Denboba Mekuria Argaw , Gebremariam Azage Gebreyohannes
Published: January 2021

Background Enset-Based land use system (EBLUS) exhibits good carbon stock and infiltration rate equivalent to forest covered areas, which enhances infiltration and water holding capacity and it can reduce the curve number (CN) of the watersheds but it was not considered in former studies. Therefore, this study is planned to model the hydrologic soil group (HSG) based CN matrix of EBLUS relative to other LUSs with established hydrological characteristics in the Meki river watershed. The soil data is used to determine the HSG of the watershed collected from Ministry of Water, Irrigation and Energy (MOWIE) and verified by Harmonized World Soil Database (HWSD). A Model is developed for CN of EBLUS relative to other LUSs (Alemu’s formula). The model considers both infiltration rate measured using Amozi-meter and carbon stoke of soil weighed as 85% and 15% respectively. HEC-GEO-HMS model is used to consider the CN of EBLUS as a separate LUS to verify the developed CN matrix model to generate CN of the sub-watersheds. Result The field measurement results show that an infiltration rate of 12.9675,11.1875,10.375,7.065 and 12.8125mm hr -1 for Natural Forest, Grassland and plantation, cultivated, built-up and EBLUS respectively. The model is: and the resulting CN matrix of EBLUS is 39,51.5,58.3 and 61.6 for HSG of A,B,C and D respectively. Conclusion Significant reduction in mean CN of the watershed that shows the role of EBLUS in managing the water resources and flood is high. Therefore, escalating EBLUS will reduce the CN of the watershed which reduces runoff volume in the watershed and it ensures the sustainability of Lake Ziway by reducing sedimentation.
Effects of Co-exposure to Lead and Manganese on Learning and Memory Deficits
Authors: Guan Rui-Li , Wang Tao , Dong Xiao-Ru , Du Ke-Jun , Li Juan , Zhao Fang , Xu Jie , Li Bin , Zheng Gang , Shen Xue-Feng , Cao Bao-Hua , Wang Jing , Aschner Michael , Liu Ming Chao , Chen Rui
Published: January 2021

Background: Lead and manganese are common neurotoxins. However, individuals are subject to co-exposures in real life, and it is therefore important to study these metals in combination. Methods: Weaning Sprague-Dawley rats were given ad libitum access to drinking water solutions containing lead (100 ppm), manganese (2.5 mg/mL) or a mixture, and each treatment has its own minocycline (50 mg/Kg.d) supplement group. Results: The results showed a significant difference in spatial memory and the induction levels of hippocampal long-term potentiation (LTP) in all exposure groups when compared with controls. The combined exposure group exhibited the most pronounced effect when compared with each of the single metal exposure groups. Microglia displayed activation at day 3 after exposure alone or in combination, while astrocytes showed activation at day 5, accompanied by decreased expression levels of glutamate/aspartate transporter (GLAST), glutamate transporter-1 (GLT-1), and glutamine synthetase (GS). Furthermore, the levels of the glutamate in the synaptic cleft increased significantly. When microglial activation was inhibited by minocycline, the activation of astrocytes, and the expression of GLAST, GLT-1, and GS were both reversed. In addition, upon minocycline treatment, the hippocampal LTP impairment and the cognitive injury were significantly alleviated in each of the exposure groups. Conclusions: These results suggest that combined exposure to lead and manganese can cause greater effects on cognition and synaptic plasticity when compared to single metal exposure groups. And the reason may involve in microglia abnormal activation leading to an excessive regulation of astrocytes, resulting in glutamate reuptake dysfunction in astrocytes and lead to perturbed cognition and synaptic plasticity.
A Multicentre Observational Psoriatic Arthritis Cohort Study Addressing Real-life Outcomes of a Treat to Target Approach in Routine Clinical Practice.
Authors: Coates Laura , Tillett William , Jadon Deepak , Rombach Ines , Tucker Laura , Watson Marion , Francis Anne , Sinomati Yvonne , Eldridge Lucy , Dritsaki Melina , Dutton Susan , Al-Mossawi Hussein , Gullick Nicola , Thompson Ben
Published: January 2021

BackgroundThe Tight Control of psoriatic arthritis (TICOPA) trial confirmed improved clinical outcomes with a treat to target (T2T) strategy in PsA. This consisted of 4-weekly review and escalation of ‘step up’ therapy (single disease modifying therapy (DMARD), combination DMARDs and then biologics) based on remission criteria. Based on this, a T2T approach is supported by European PsA treatment recommendations. However, it is not commonly implemented in routine care primarily due to feasibility and cost concerns. In the TICOPA trial, the same treatment regime was used for all participants regardless of their disease profile. Despite the recognition of PsA as a highly heterogenous condition no studies have tailored which drugs are used depending on disease severity. The cohort will establish real world outcomes for the T2T approach in PsA and also form the basis of a trials within cohorts (TWiCs) design to test alternative therapeutic approaches within embedded clinical trials providing an evidence base for treatment strategy in PsA.MethodsThe Multicentre Observational Initiative in Treat to target Outcomes in Psoriatic Arthritis (MONITOR-PsA) cohort will apply a T2T approach within routine care. It will recruit newly diagnosed adult patients with PsA starting systemic therapies. The cohort is observational allowing routine therapeutic care within NHS clinics but a T2T approach will be supported when monitoring treatment within the cohort. Eligible participants will be adults (≥18 years) with active PsA with ≥1 tender or swollen joints or enthesis who have not previously had treatment with DMARDs for articular disease.DiscussionThis study is the first TWiC designed to support a fully powered randomized drug trial. The results from the observational cohort will be compared with those observed in the TICOPA trial investigating the clinical effectiveness and health care costs of the pragmatic T2T approach. Nested trials will provide definitive RCT evidence establishing the optimal management of PsA within the T2T approach. The TWiCs design allows robust generalizability to routine healthcare, avoids disappointment bias, aids recruitment and in future will allow assessment of longer term outcomes.Trial registrationNCT03531073, retrospectively registered 21 May 2018
A Randomized, Controlled Study on the Safety and Efficacy of Maraviroc and/or Favipiravir Vs Currently Used Therapy in Severe COVID-19 Adults. (COMVIVIR, clinicaltrials.gov NCT04475991)
Authors: Perez-Garcia Adolfo , Villalobos-Osnaya Alma , Hernández-Medel María Luisa , Pérez-Navarro Lucía Monserrat , Medina-Hernández Elba O. , Cabrera-Orejuela Diana Sofía , Espinosa-García Ana María , Solleiro-Villavicencio Elena , León-Hernández Mireya , Mayor Arianna Rodríguez-Cal y , Servín-Murillo Manli M. , Reyes-Terán Gustavo , Sierra-Madero Juan , Oca Gonzalo Salgado-Montes de , Ávila-Ríos Santiango , López-Alvarenga Juan Carlos , Serrano-Loyola Raúl , Guerrero-Avendaño Guadalupe Mercedes Lucía , Hernández-Ruiz Joselín
Published: January 2021

Background: Multiple studies have now established that hyperinflammatory response induced by SARS CoV-2 is a main cause of complications and death in infected subjects. Such dysfunctional immune response has been described as a dysregulated and exacerbated production of cytokines and chemokines that attracts and activates inflammatory cells, which start and sustain pulmonary and systemic damage, thus causing complications that lead to multi organ failure and death. Therefore, we suggest that blocking key inflammation receptors could help to reduce migration and activation of Th17, monocytes/macrophages and neutrophils, thus mitigating the cytokine storm and averting severe complications and death. Importantly, the optimum treatment for COVID-19 severe patients could combine a modulator of the immune response with a direct antiviral drug against SARS-CoV-2, in order to address both the viral load and the hyperinflammatory effects of the immune dysregulation.Methods: Maraviroc (MVC), a CCR5 antagonist, and Favipiravir (FPV), an antiviral, will be evaluated single and combined, added to the treatment currently used at the Hospital General de México for severe non-critical COVID-19 patients. One hundred patients will be allocated in four arms [Current treatment only (CT), CT+MVC, CT+FPV, CT+MVC+FPV]. Percentage of patients free of mechanical ventilation or death at day 28, immunophenotyping and viral load will be compared between groupsDiscussion: New immune focused therapies are targeting strong inflammation mediators such as IL-6 and IL1-B; nevertheless, to our best knowledge, controlling chemotaxis has not been explored. The use of a drug therapy that addresses both the regulation of the immune response and the inhibition of viral replication could at the same time, help to alleviate the hyperinflammatory condition and reduce the time of the viral clearance process, therefore improving treatment outcomesTrial registration: Clinical Trials (www.clinicaltrials.gov) NCT: 04475991.
Disorders of Sex Development in Wolf-Hirschhorn Syndrome: A Genotype-phenotype Correlation and MSX1 as Candidate Gene
Authors: Rjiba Khouloud , Ayech Hedia , Slimani Wafa , KRAIEM Olfa , Jelloul Afef , Hmida Imen Ben Hadj , Mahdhaoui Nabiha , Saad Ali , Mougou-Zerelli Soumaya
Published: January 2021

Background: Wolf-Hirschhorn (WHS) is a set of congenital physical anomalies and mental retardation associated with a partial deletion of the short arm of chromosome 4.To establish a genotype-phenotype correlation; we carried out a molecular cytogenetic analysis on two Tunisian WHS patients. Patient 1was a boy of one-year-old presented typical WHS phenotype while patient 2, is a boy of two days presented an hypospadias, a micropenis and cryptorchidie in addition to the typical WHS phenotype. Both the comparative genomic hybridization (CGH array) and Fluorescence in Situ Hybridization (FISH) techniques were used.Results: Results of the analysis showed that patient 2 had a greater deletion size (4,8Mb) of chromosome 4 than patient 1 (3, 4 Mb). Here, we notice that the larger the deletion, the more genes are likely to be involved, and the more severe the phenotype is likely to be. If we analyze the uncommon deleted region between patient1 and patient 2 we found that the Muscle Segment Homeobox (MSX1) gene is included in this region. MSX1 is a critical transcriptional repressor factor, expressed in the ventral side of the developing anterior pituitary and implicated in gonadotrope differentiation. Msx acts as a negative regulatory pituitary development by repressing the gonadotropin releasing hormone (GnRH) genes during embryogenesis. We hypothesized that the deletion of MSX1 in our patient may deregulate the androgen synthesis. Conclusion: Based on the MSX1 gene function, its absence might be indirectly responsible for the hypospadias phenotype by contributing to the spatiotemporal regulation of GnRH transcription during development.
Whole-exome Sequencing Identified a Novel Heterozygous Mutation of SALL1 and a New Homozygous Mutation of PTPRQ in a Chinese Family With Townes-brocks Syndrome and Hearing Loss
Authors: Guangxian Yang , Yi Yin , Zhiping Tan , Jian Liu , Xicheng Deng , Yifeng Yang
Published: January 2021

Background: Previous studies have revealed that mutations of Spalt Like Transcription Factor 1 (SALL1) are responsible for Townes-Brocks syndrome (TBS), a rare genetic disorder that is characterized by an imperforate anus, dysplastic ears, thumb malformations and other abnormalities, such as hearing loss, foot malformations, renal impairment with or without renal malformations, genitourinary malformations, and congenital heart disease (CHD). In addition, the protein tyrosine phosphatase receptor type Q (PTPRQ) gene has been identified in nonsyndromic hearing loss patients with autosomal recessive or autosomal dominant inherited patterns.Methods: A Chinese family with TBS and hearing loss was enrolled in this study. The proband was a two-month-old girl who suffered from congenital anal atresia with rectal perineal fistula, ventricular septal defect, patent ductus arteriosus, pulmonary hypertension (PH), and finger deformities. The proband’s father also had external ear deformity with deafness, toe deformities and PH, although his anus was normal. Further investigation found that the proband’s mother presented nonsyndromic hearing loss, and the proband’s mother’s parents were consanguine married. Whole-exome sequencing and Sanger sequencing were applied to detect the genetic lesions of TBS and nonsyndromic hearing loss.Results: Via whole-exome sequencing and Sanger sequencing of the proband and her mother, we identified a novel heterozygous mutation (ENST00000251020: c.1428_1429insT, p. K478QfsX38) of SALL1 in the proband and her father who presented TBS phenotypes, and we also detected a new homozygous mutation (ENST00000266688: c.1057_1057delC, p. L353SfsX8)) of PTPRQ in the proband’s mother and uncle, who suffered from nonsyndromic hearing loss. Both mutations were located in the conserved sites of the respective protein and were predicted to be deleterious by informatics analysis.Conclusions: This study confirmed the diagnosis of TBS at the molecular level and expanded the spectrum of SALL1 mutations and PTPRQ mutations. Our study may contribute to the clinical management and genetic counselling of TBS and hearing loss.
Applications of Bayesian Shrinkage Prior Models in Clinical Research with Categorical Responses
Authors: Bhattacharyya Arinjita , Pal Subhadip , Mitra Riten , Rai Shesh
Published: January 2021

Background: Prediction and classiﬁcation algorithms are commonly used in clinical research for identifying patients susceptible to clinical conditions like diabetes, colon cancer, and Alzheimer’s disease. Developing accurate prediction and classiﬁcation methods have implications for personalized medicine. Building an excellent predictive model involves selecting features that are most signiﬁcantly associated with the response at hand. These features can include several biological and demographic characteristics, such as genomic biomarkers and health history. Such variable selection becomes challenging when the number of potential predictors is large. Bayesian shrinkage models have emerged as popular and ﬂexible methods of variable selection in regression settings. The article discusses variable selection with three shrinkage priors and illustrates its application to clinical data sets such as Pima Indians Diabetes, Colon cancer, ADNI, and OASIS Alzheimer’s data sets. Methods: We present a uniﬁed Bayesian hierarchical framework that implements and compares shrinkage priors in binary and multinomial logistic regression models. The key feature is the representation of the likelihood by a Polya-Gamma data augmentation, which admits a natural integration with a family of shrinkage priors. We speciﬁcally focus on the Horseshoe, Dirichlet Laplace, and Double Pareto priors. Extensive simulation studies are conducted to assess the performances under diﬀerent data dimensions and parameter settings. Measures of accuracy, AUC, brier score, L1 error, cross-entropy, ROC surface plots are used as evaluation criteria comparing the priors to frequentist methods like Lasso, Elastic-Net, and Ridge regression. Results: All three priors can be used for robust prediction with signiﬁcant metrics, irrespective of their categorical response model choices. Simulation study could achieve the mean prediction accuracy of 91% (95% CI: 90.7, 91.2) and 74% (95% CI: 73.8,74.1) for logistic regression and multinomial logistic models, respectively. The model can identify signiﬁcant variables for disease risk prediction and is computationally eﬃcient. Conclusions: The models are robust enough to conduct both variable selection and future prediction because of their high shrinkage property and applicability to a broad range of classiﬁcation problems.
Identification of Bacillus Anthracis, Brucella Spp., and Coxiella Burnetii DNA Signatures From Bushmeat
Authors: Katani Robab , Schilling Megan , Lyimo Beatus , Eblate Ernest , Martin Andimile , Tonui Triza , Cattadori Isabella , Francesconi Stephen , Estes Anna , Rentsch Dennis , Sriniva Sreenidhi , Lyimo Samson , Munuo Lidia , Tiambo Christian , Stomeo Francesca , Gwakisa Paul , Mosha Fausta , Hudson Peter , Buza Joram , Kapur Vivek
Published: January 2021

Meat from wildlife species (bushmeat) represents a major source of dietary protein in low- and middle-income countries where humans and wildlife live in close proximity. Despite the occurrence of zoonotic pathogens in wildlife, their prevalence in bushmeat remains unknown. To assess the risk of exposure to major pathogens in bushmeat, a total of 3,784 samples were collected from three major regions in Tanzania during both rainy and dry seasons, both fresh and processed and screened by real-time PCR for the presence of DNA signatures of Bacillus anthracis, Brucella spp and Coxiella burnetii (Coxiella). The analysis identified DNA signatures of B. anthracis (0.48%), Brucella (0.9%), and Coxiella (0.66%) in a total of 77 samples. Highest prevalence rates of B. anthracis, Brucella, and Coxiella were observed in wildebeest, dik-dik, and impala, respectively. Fresh samples, those collected during the rainy season, and samples from Selous or the Serengeti had a greater relative risk of being positive. Microbiome characterization identified Firmicutes and Proteobacteria as the most abundant phyla. The results highlight and define potential risks of exposure to endemic wildlife diseases from bushmeat and the need for future investigations to address the public health and emerging infectious disease risks associated with bushmeat harvesting, trade, and consumption.
Low-Light Image Enhancement Base on Brightness Attention Mechanism Generative Adversarial Networks
Authors: Wang Chunzhi , Ma Zeyu , Fu Jiarun , Gao Rong , Ling Hefei , Yan Lingyu
Published: January 2021

With the development of intelligent technology, the concept of smart city, which is used to optimize urban management and services and improve the quality of life of citizens, has gradually been integrated into human social life. However, dark lighting environments in reality, such as insufficient light at night, cause or block photographic images in low brightness, severe noise, and a large number of details are lost, resulting in a huge loss of image content and information, which hinders further analysis and use. Such problems not only exist in the development of smart cities, but also exist in traditional criminal investigation, scientific photography and other fields, such as the accuracy of low-light image. However, in the current research results, there is no perfect means to deal with the above problems. Therefore, the study of low-light image enhancement has important theoretical significance and practical application value for the development of smart cities. In order to improve the quality of low-light enhanced images, this paper tries to introduce the luminance attention mechanism to improve the enhancement efficiency. The main contents of this paper are summarized as follows: using the attention mechanism, a method of low-light image enhancement based on the brightness attention mechanism to generative adversarial networks is proposed. This method uses brightness attention mechanism to predict the illumination distribution of low-light image and guides the enhancement network to enhance the image adaptiveness in different luminance regions. At the same time, u-NET network is designed and constructed to improve the modeling process of low-light image. We verified the performance of the algorithm on the synthetic data set and compared it with traditional image enhancement methods (HE, SRIE) and deep learning methods (DSLR). The experimental results show that our proposed network model has relatively good enhancement quality for low-light images, and improves the overall robustness, which has practical significance for solving the problem of low-light image enhancement in smart cities.
Deubiquitination and Stabilization of PD-L1 by USP21
Authors: Yang Shuying , Wu Youqian , Yan Huanhuan , Shan Bing , Zhou Dongheng , Liu Xiaolan , Mao Xinli , Zhou Shenkang , Zhao Qingwei , Xia Hongguang
Published: January 2021

Background: The immunotherapy for different types of cancers that targeting programmed death protein-1 (PD-1) and programmed death ligand-1 (PD-L1) has highlighted the importance of suppressing specific T cell responses. Recently, several studies have shown that the expression level of PD-L1 in tumor cells is positively correlated with tumor metastasis as well as recurrence rate. The potent effects of post-translational modifications (PTMs) for PD-L1, such as ubiquitination, glycosylation, phosphorylation and palmitoylation, have been reported to be related to immunosuppression. However, the regulation of PD-L1 degradation in cancers is still not well understood. In this paper, we mainly investigate the deubiquitination regulation of PD-L1. Methods: The protein levels of PD-L1 and USP21 were detected by Immunoblotting and immunohistochemistry. The interaction between PD-L1 and USP21 was determined by co-immunoprecipitation. The deubiquitination of PD-L1 was determined by in vitro deubiquitination assay. The deubiquitination sites of PD-L1 were identified by mass spectrometry analysis. The expression of mRNA in target tissues was presented by bioinformatics analysis.Results: Overexpression of USP21 significantly increased PD-L1 abundance and knockdown of USP21 induced degradation of PD-L1. In vitro deubiquitination assay showed that USP21-WT reduced polyubiquitin chains from PD-L1 while USP21-C221A did not. Furthermore, five lysines in intracellular segment of PD-L1 are potential deubiquitin sites and cancer-derived mutations of PD-L1 in Asp276 have the ability to enhance the deubiquitination of PD-L1 mediated by USP21. Finally, we found that USP21 is the frequently amplified deubiquitinase in lung cancer, especially in lung squamous cell carcinoma, and its amplification co-occurs with the upregulation of PD-L1 levels. Moreover, IHC analysis showed stronger staining of PD-L1 and USP21 in lung cancer samples than adjacent tissues. Conclusion: We identified USP21 as a novel deubiquitinase of PD-L1. Hopefully, targeting PD-L1 by inhibiting USP21 might be a potentially novel strategy for the treatment of lung cancer.
Circulating Mature Granzyme B+ T Cells Distinguish Crohn’s Disease Associated Axial Spondyloarthritis from Axial Spondyloarthritis and Crohn’s Disease
Authors: Lefferts Adam R. , Regner Emilie H. , Stahly Andrew , O'Rourke Becky , Gerich Mark E. , Fennimore Blair P. , Scott Frank I. , Freeman Alison E. , Jones Ken , Kuhn Kristine
Published: January 2021

Background: Axial spondyloarthritis (axSpA) has strong connections with intestinal inflammation as occurs in Crohn’s disease (CD). However, the immunologic mechanisms that distinguish axSpA, CD, and those with features of both diseases (CD-axSpA) are unknown. This study aimed to address this question by initial unbiased single cell RNA-sequencing (scRNAseq) on a pilot cohort followed by validating findings using flow cytometry and ELISA in a larger cohort. Methods: Two individuals each with CD, axSpA, CD-axSpA, and healthy controls (HC) were recruited for a pilot discovery scRNAseq cohort, and the validation cohort consisted of 18 axSpA, 24 CD, 13 CD-axSpA, and 17 HC that was evaluated by flow cytometry on PBMCs and ELISAs for plasma cytokines. Results: Uniquely, PBMCs from subjects with CD-axSpA demonstrated a significant increase in granzyme B+ T cells of both CD4+ and CD8+ lineages by both scRNAseq and flow cytometry. T cell maturation was also greater in those with CD-axSpA, particularly the CD4+ granzyme B+ population. Pathway analysis suggested increased interferon response genes in all immune cell populations within CD-axSpA. Although IFN-g was elevated in the plasma of a subset of subjects with CD-axSpA, IL-6 was also significantly elevated. Conclusions: Our findings support the presence of a chronic interferonopathy in subjects with CD-axSpA characterized by interferon signaling by pathway analysis and an expansion of mature, cytotoxic T cells. These data indicate fundamental immunological differences between CD-axSpA and both of the putative “parent” conditions, suggesting that it is a distinct disease with unique natural history and treatment needs.
Application value of contrast-enhanced ultrasound in the diagnosis of intermediate trophoblastic tumours
Authors: Zhu XiaoDan , Hu Yin , Zhou Linyu , Jiang Tian'an
Published: January 2021

Background
Through the research and analysis of colour Doppler ultrasound images (CDFIs) and contrast-enhanced ultrasonography (CEUS) images of intermediate trophoblastic tumours (ITTs), the ultrasound characteristics and CEUS perfusion characteristics are summarized, and these findings can provide a reference for the correct diagnosis of ITTs.
Methods
Seven ITT patients were diagnosed and treated in our institution from January 2016 to August 2020, and their clinical characteristics and ultrasound image characteristics were studied.
Results
The most common clinical symptoms of an ITT are vaginal bleeding and menopause. In the study, 6 patients had a history of menopause, 5 patients had irregular vaginal bleeding, and 1 patient was asymptomatic. The serum ß-human chorionic gonadotropin (ß-hCG) level was mainly a low-grade increase, and the average level was approximately 8167 IU/L. However, the ß-hCG level in one patient with lung metastasis was not high (53.2 IU/L), and the ß-hCG level in the other patient with ovarian and bladder metastases was high (55422.2 IU/L). In grey-scale ultrasound, ITTs can be divided into 3 types: type I, where most of the lesions protrude into the uterine cavity (2 patients); type II, where the lesions are partly located in the uterine cavity and partly in the muscle layer (3 patients); and type III, where the lesions are limited to the myometrium (2 patients). The internal echo of the lesion can be divided into solid and cystic-solid echo. CDFI shows that blood flow signals from minimal to abundant. The enhancement mode of CEUS is mainly regional enhancement (5 patients), the arterial phase is mainly slow and equal-slightly high enhancement (6 patients), and the enhancement boundary is not clear (6 patients).
Conclusions
Certain characteristic changes in CEUS of ITTs, combined with clinical features, can provide help for the accurate diagnosis of ITT.