bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blue light attenuates TGF-β2-induced epithelial-mesenchymal transition in human lens epithelial cells via autophagy impairment
Authors: Zhang Dongyan , Zhu Hong , Yu Xin , Wang Liyin , Wen Yingying , Zhang Liyue , Tong Jianping , Shen Ye 
Published: July 2022

Abstract
Background: Pathogenesis of posterior capsular opacification (PCO) was related to pathological epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs). It has been reported that blue light could have an effect on EMT. This study aims to elucidate the role and potential mechanism of autophagy in EMT after blue light exposure in LECs.Methods: HLE-B3 cells were treated with TGF-β2 with different concentration and time to induce EMT as a model of PCO in vitro. Cells were exposed to blue light with or without TGF-β2. The expression levels of EMT-associated markers were analyzed by qRT-PCR, western blotting and cell migration ability was determined by transwell migration assay and wound healing assay. The expressions of autophagy-related proteins were analyzed by western blotting, immunofluorescence and transmission electron microscopy. Rapamycin and chloroquine were utilized in cells for autophagy activation and inhibition.Results: TGF-β2 induced autophagy activation during EMT progression in HLE-B3 cells in a dose- and time-dependent manner. Blue light exposure inhibited TGF-β2-induced EMT characterized by inhibited expression of EMT related markers and reduced migration. Meanwhile, blue light exposure impaired autophagy activated by TGF-β2. Furthermore, Autophagy activation with rapamycin rescued EMT attenuated by blue light. Autophagy inhibition with chloroquine reduced TGF-β2-induced EMT in HLE-B3 cells.Conclusion: Blue light exposure had inhibited effects on TGF-β2-induced EMT in LECs through autophagy impairment, which provides a new insight on prevention and treatment of PCO.
How to define a Puumala hantavirus outbreak?
Authors: Kazasidis Orestis , Jacob Jens 
Published: July 2022

Abstract
Human Puumala virus (PUUV) infections in Germany fluctuate multi-annually, following fluctuations of the bank vole population size. We applied a transformation to the annual incidence values and established a heuristic method to develop a straightforward robust model for the binary human infection risk at the district level. The classification model was powered by a machine-learning algorithm and achieved 85% sensitivity and 71% precision, despite using only three weather parameters from the previous years as inputs, namely the soil temperature in April of two years before and in September of the previous year, and the sunshine duration in September of two years before. Moreover, we introduced the PUUV Outbreak Index that quantifies the spatial synchrony of local PUUV-outbreaks, and applied it to the seven reported outbreaks in the period 2006–2021. Finally, we used the classification model to estimate the PUUV Outbreak Index, achieving 20% maximum uncertainty.
An in-silica computation of alpha oscillations from apparently unrelated psychophysics data
Authors: Ghosh Kuntal , Chandran Keerthi S 
Published: July 2022

Abstract
The ten hertz alpha oscillations are the strongest rhythmic encodings from human brain. They arise from occipital lobes and are connected with visual perception and visual cognition. A flicker stimulus can also evoke oscillations in human EEG that are of the same frequency as the flicker stimulus. The oscillations are evoked even when there is no conscious perception of the flicker stimulus. The oscillations so evoked show resonances at 10, 20, 40 and 80 hertz. When a subject is not able to perceive the flicker and the source appears as a steady source of light, flicker fusion is said to have occurred. Psychophysics experiments on flicker fusion involves presenting a human subject with a flicker stimulus, and the subject classifying the stimulus as either flickering or fused. The physical parameters associated with the stimulus that determines whether the stimulus is classified as flickering or fused by the subject, are varied in psychophysics experiments. Deep neural networks, on the other hand, have been proposed as a model for cognition and perception that can make falsifiable predictions. In this work, motivated by the feedforward and feedback visual pathways, we propose a deep convolutional recurrent neural network model that may be trained using psychophysics data. The neural network takes the time series representation of the flicker stimulus as input, and the binary classification made by the subject on whether stimulus appears flickering or fused, is set as the output. We show that an intermediate convolution layer of such a recurrent neural network trained on psychophysics data can give sinusoidal output on the input of a representation of ten hertz stimulus, signifying that an in-silica computation of alpha oscillations is possible through such a network.
A gated group sequential design for seamless Phase II/III trial with subpopulation selection
Authors: Miao Guanhong , Liao Jason J.Z. , Yang Jing , Anderson Keaven 
Published: July 2022

Abstract
Background: Due to the high cost and high failure rate of Phase III trials, seamless Phase II/III designs are more and more popular to trial efficiency. A potential attraction of Phase II/III design is to allow a randomized proof-of-concept stage prior to committing to the full cost of the Phase III trial. Population selection during the trial allows a trial to adapt and focus investment where it is most likely to provide patient beneﬁt. Methods: Motivated by a clinical trial to ﬁnd the population that potential beneﬁts with dual-primary endpoints progression free survival (PFS) and overall survival (OS), we propose a gated group sequential design for a seamless Phase II/III trial design with population selection. Results: The investigated design controls the familywise error rate and allows multiple interim analyses to enable early stopping for efficacy or futility. Simulations and an illustrative example suggest that the proposed gated group sequential design can have more power than the commonly used classical group sequential design, and reduces the patient’s exposure to less effective treatment if the complementary sub-group has less significant treatment effect. Conclusions: The proposed gated group sequential design controls the familywise error rate and allows multiple interim analyses to enable early stopping for efficacy or futility. It has the potential to save drug development cost and more quickly fulfill unmet medical needs.
User Engagement Metrics and Patterns in Phendo, an Endometriosis Research Mobile App
Authors: Elhadad Noemie , Urteaga Iñigo , Lipsky-Gorman Sharon , McKillop Mollie 
Published: July 2022

Abstract
We characterize short-term and long-term user engagement patterns in a self-tracking, mobile health app. We introduce and define engagement metrics to capture the quantity, duration, and density of participant engagement according to different domains of self-tracking. We focus our study on Phendo, a research app designed for participants to self-track their experiences of endometriosis ---a chronic disease in women of reproductive age.

Given a cohort of Phendo participants with at least one initial week of use, we analyze their engagement patterns based on amount and timing of daily app usage and stratify them according to their short-term engagement patterns, i.e., within their first 12 weeks of app-use. Given the overall cohort and its stratified short-term participant engagement groups, we then assess overall longitudinal engagement patterns with the app beyond the first 12 weeks, as well as with disease-specific self-tracking domain types.

We identify four groups of participants in the Phendo cohort (n=4,993) according to their short-term engagement: Regulars, Usuals, Occasionals, and Seldoms. Participants across the groups do not differ in disease status or demographics, except for age and education. We find that, while the stratification is based on a short-term period, the groups continue to exhibit distinct longitudinal engagement patterns in the long-term (up to 4 years). We also find that Regulars are more likely to engage with self-tracking related to disease self-management than the other groups.

These findings have implications for the design of research mobile apps, as certain functionalities like tracking of self-management, might yield longer and richer engagement with certain types of participants, even if self-management is not part of the original intent of the research app. More broadly, our proposed engagement metrics and analyses provide a roadmap for exploring participant engagement patterns in mobile research apps.
Methodology to incorporate seismic damage and debris to evaluate strategies to reduce life safety risk for multi-hazard earthquake and tsunami
Authors: Amini Mehrshad , Sanderson Dylan R. , Cox Daniel. T. , Barbosa Andre R. , Rosenheim Nathanael 
Published: July 2022

Abstract
This paper presents a methodology to evaluate life safety risk of coastal communities vulnerable to seismic and tsunami hazards. The work explicitly incorporates two important aspects in tsunami evacuation modeling: (1) the effect of earthquake-induced damage to buildings on building egress time, (2) the effect of earthquake-induced debris on horizontal evacuation time. The city of Seaside, Oregon, is selected as a testbed community. The hazard is based on a megathrust earthquake and tsunami from the Cascadia Subduction Zone that was defined in a previous study. The built environment consists of buildings and the transportation network for the city. Fragility analysis is used to estimate the seismic damage to buildings and resulting debris that covers portions of the road network. The horizontal evacuation time is determined based on the shortest path to shelters, including the increased travel time due to the earthquake-generated debris. The effects of different mitigation strategies are quantified. Results indicate the fatality and life safety risk of a near-field tsunami increases by 4.2 to 8.3 times when the effects of building egress and earthquake-induced debris are considered. The choice of population layer affects the life safety risk and thus the maximum risk is obtained when daytime populations are considered. Use of mitigation strategies result in a significant decrease in the number of fatalities. For hazards with recurrence intervals larger than 500-years, the vertical evacuation is the most effective strategy in reducing fatalities and associated risks. Implementing all mitigation strategies reduces the life safety risk by 90%.
Can Dysphagia Aspiration Related Structures (DARS) Be Spared In Patients With Oropharyngeal Cancers? Dosimetric Evaluation In A Prospective Study Of DARS Optimized Intensity Modulated Radiation Therapy
Authors: Calcuttawala Adnan , Shinghal Abhishek , Budrukkar Ashwini , Swain Monali , Murthy Vedang , Laskar Sarbani Ghosh , Gupta Tejpal , Upereti Rituraj , Kale Shrikant , Agarwal Jai Prakash 
Published: July 2022

Abstract
Background: The dysphagia-aspiration related structures (DARS) play an integral role in the normal swallowing mechanism. This study was done with the purpose of evaluating the feasibility of sparing DARS in various head and neck cancer sites treated with definitive DARS optimized intensity modulated radiation therapy (IMRT) and concurrent chemotherapy.Methods: Target volumes, organs at risk and in addition individual DARS were delineated including the superior, middle, and inferior pharyngeal constrictor muscles, supraglottic and glottic larynx, base of tongue, esophageal inlet muscles and cervical esophagus in 35 patients with head and neck squamous cell carcinoma. Volume based dose constraints were applied to the DARS outside the planning target volume (PTV). IMRT plan was then generated to limit doses to DARS without compromising PTV dose coverage. Results: Twelve (34.3%) patients had an oropharyngeal primary (OPX),18 (51.4%) had a laryngeal and 5 (14.3%) patients had hypophyaryngeal primary. The mean dose to the DARS was 47.93Gy for the entire group while it was 54.6Gy in oropharyngeal primaries and 44.4Gy in laryngopharyngeal primaries. DARS mean dose of ≤45Gy could be achieved in a significantly lesser number of patients with oropharyngeal primaries (p<0.02). Similarly, DARS mean dose was 42.25Gy in patients with N0 disease, 49.6Gy with ipsilateral involved nodes, and 55Gy with bilateral disease. Sparing of DARS was feasible when the volume of PTV was ≤150cc (p<0.025).Conclusion: Sparing of DARS structures appears to be challenging in patients with oropharyngeal cancers without compromising the dose to the PTVs while it is feasible in laryngeal and hypopharyngeal cancers. DARS sparing is feasible when the PTV volume is ≤150cc and in patients with negative or unilateral nodal disease.Trial Registration: This study was registered retrospectively with the Clinical Trials Registry of India on 9th November 2017. The registration number is CTRI/2017/11/010442.
A Novel Loss of Function Variant of SLC19A1 Presented with Immunodeficiency and Benefited from Folinic Acid Treatment
Authors: Gök Veysel , Erdem Şerife , Haliloğlu Yeşim , Bişgin Atil , Belkaya Serkan , Başaran Kemal Erdem , Özcan Alper , Yılmaz Ebru , Acıpayam Can , Karakükcü Musa , Canatan Halit , Per Hüseyin , Patıroğlu Türkan , Eken Ahmet , Ünal Ekrem 
Published: July 2022

Abstract
Insufficient dietary folate intake, hereditary malabsorption, or defects in folate metabolism may lead to combined immunodeficiency (CID). Although loss of function mutations in the major intestinal folate transporter PCFT/SLC46A1 was shown to be associated with CID, the evidence for pathogenic variants of RFC/SLC19A1 resulting in immunodeficiency was lacking. In this study, we report two cousins carrying a homozygous pathogenic variant c.1042G>A, resulting in p.G348R substitution who showed clinical symptoms of immunodeficiency associated with defects of folate metabolism. The mutation was identified by whole-exome sequencing. SLC19A1 expression by peripheral blood mononuclear cells (PBMC) was quantified by real-time qPCR and immunostaining. T cell proliferation, methotrexate resistance, NK cell cytotoxicity, Treg cells and cytokine production by T cells were examined by flow cytometric assays. Both patients were treated with and clinically benefited from folinic acid (FA). Functional studies revealed normal NK cell cytotoxicity, Treg cell counts, and naive-memory T cell percentages. Although SLC19A1 mRNA and protein expression were unaltered, remarkably, mitogen induced-T cell proliferation was significantly reduced at sub- and supraoptimal folic acid concentrations. In addition, both patients’ PBMCs were resistant to methotrexate-induced apoptosis supporting a functionally defective SLC19A1 variant. This study, to our knowledge, presents the second pathogenic SLC19A1 variant in the literature, providing the first experimental evidence that loss of function mutations in SLC19A1 may present with symptoms of immunodeficiency, and that those defects could benefit from FA supplementation.
Effects of sodium para-aminosalicylic acid on chelation treatment in Pb-exposed mice
Authors: Li Yan , Liang Yuan , Fang Yuan-yuan , Chen Jing , Zheng Xiao-wei , Zhou Wu-wang , Lu Li-li , Aschner Michael , Ou Shi-yan , Jiang Yue-ming 
Published: July 2022

Abstract
Lead (Pb) is a corrosion-resistant, heavy, non-ferrous metal with widespread environmental pollution. Several metal chelators have been used in the treatment of Pb poisoning. However, the effect of sodium para-aminosalicylic acid（PAS-Na）on Pb excretion has yet to be reported. To investigate the effects of PAS-Na on Pb excretion, a mouse model of acute lead exposure was established. Healthy mice (90) received abdominal injection (i.p.) of 120 mg/kg Pb acetate, and 4 h later 80, 160, 240 mg/kg PAS-Na, or 240 mg/kg edetate calcium disodium (CaNa2EDTA) were injected subcutaneously (s.c.) once per day for 6 days into the corresponding groups, respectively. The Control, Pb-exposed, PAS-Na and CaNa2EDTA groups were evaluated simultaneously. After collecting 24 h urine samples, the animals were sacrificed in batches on the 2nd, 4th, 6th day. Levels of Pb and other metal elements [including manganese (Mn) and copper (Cu)] in the urine, whole blood and brain tissues were analyzed by graphite furnace atomic absorption spectrometry (AAS). The results showed that lead exposure increased Pb levels in urine and blood of mice, and PAS-Na treatment afforded antagonistic effect against Pb-induced toxicity. While additional studies will be needed, these novel results establish PAS-Na as a potential efficacious treatment for mitigating Pb-induced toxicity.
Topography Optimization of Cylindrical Shells With Cutouts for Maximum Buckling Strength
Authors: Gokyer Yusuf , Sonmez Fazil O. 
Published: July 2022

Abstract
In the presence of cutouts, the buckling strength of shell structures under compression significantly decreases. In order to compensate this, these structures are reinforced with stiffeners. In this study, the objective is to optimize the stiffener geometry and pattern on a cylindrical shell with two square holes to maximize the buckling load capacity without increase in its weight. A finite element model is developed to evaluate the buckling load of the structure. A good correlation is observed between the nonlinear analysis results of the model and the numerical and experimental results reported in the literature. Optimization is achieved in two levels. In the first level, topography optimization is performed to obtain the optimal stiffener pattern over the shell surface based on linear eigenvalue buckling analysis. In the second level, the stiffener heights and the shell thickness are optimized using a local search algorithm, Nelder-Mead; the buckling load levels are obtained by carrying out nonlinear buckling analyses in ANSYS. A Python code is developed to implement the optimization method and conduct analyses in ANSYS. The results show that stiffeners need to be introduced around the cutouts and the regions near the top and bottom edges for maximum buckling load capacity. The results also reveal that stiffeners on the mid lateral surfaces of the cylinder do not make significant contribution to the buckling strength. The bucking load of the optimized stiffened geometry is 22% higher than that of the unreinforced geometry having the same weight.
Discovery of Two-Dimensional Binary Nanoparticle Superlattices Using Global Monte Carlo Optimization
Authors: Zhou Yilong , Arya Gaurav 
Published: July 2022

Abstract
Binary nanoparticle (NP) superlattices exhibit distinct collective plasmonic, magnetic, optical, and electronic properties. Here, we demonstrate how fluid-fluid interfaces could be used to self- assemble binary systems of NPs into 2D superlattices when the NP species exhibit different miscibility with the fluids forming the interface. We develop a basin-hopping Monte Carlo algorithm tailored for interface-trapped structures to rapidly determine the ground-state configuration of NPs, allowing us to explore the repertoire of binary NP architectures formed at the interface. By varying the NP size ratio, interparticle interaction strength, and difference in NP miscibility with the two fluids, we demonstrate the assembly of an array of exquisite 2D periodic architectures, including AB-, AB2-, and AB3-type monolayer superlattices as well as AB-, A3B5-, and A4B6-type bilayer superlattices. Our results suggest that the interfacial assembly approach could be a versatile platform for fabricating 2D colloidal superlattices with tunable structure and properties.
Scientific strategies associated with mitigating the challenges in predicting track and intensity of cyclones across the world basins
Authors: Singh Vivek 
Published: July 2022

Abstract
The present study analyses the scientific strategies associated with mitigating the challenges in predicting track and intensity of cyclones across the world basins. The relevant ‘51’ original publications on predicting track and intensity of cyclones across the world basins utilising numerical weather prediction (NWP) models, machine learning and satellite based approach were chosen using a focused orderly search and were used to develop the selection benchmarks for the systematic literature review. According to our review, out of selected ‘51’ studies, a total of ‘19’(37.25%) and ‘12’ (23.52%) and ‘9’ (17.64%) studies were focused on Pacific (including south China sea) Atlantic and North Indian Ocean (NIO) basins respectively. Three studies were conducted over both the Pacific and Atlantic Basins. However, the remaining ‘8’ studies were not over any specific basin. After 2015, the widespread use of machine based algorithm and analysis began, with a focus on the improvement in intensity prediction of TCs. Satellite based approach was employed in nearly all of the studies, and data assimilation techniques were in nascent stage during 2006-2013. To create detailed cyclone prediction track and intensity of cyclones across the world basins, a balance among data assimilation systems, modelling systems, and machine learning to uncover predictability drivers is necessary. Globally, predicting track and intensity of cyclones should take into account future climate change scenarios in the world basins. In order to gain improvement in this direction, further research is needed to fill in the knowledge gaps that have been identified.
REDE DE ATENÇÃO DO SUS À SAÚDE DA PESSOA COM DEFICIÊNCIA E A COVID — 19
Authors: Joheny Clara 
Published: July 2022

RESUMO

Este trabalho tem o intuito de estudar as leis, diretrizes e bases da rede de atenção à saúde da pessoa com deficiência no âmbito do sistema único de saúde – SUS e os desafios enfrentados pelas pessoas com deficiência em meio a pandemia Corona — vírus nos atuais anos de 2020 e 2021. Trata-se de um estudo bibliográfico descritivo iniciado e realizado no período da pandemia com base em livros, artigos, site oficial do Ministério da Saúde, Organização Mundial de Saúde — OMS e revistas que acompanham e publicam sobre a temática no território brasileiro. diante disso, por entender que a maioria da população não tem acesso a todos serviços de atendimento saúde, por conta da precariedade, nos atendimentos. Este trabalho tornou-se fundamental para esclarecer possíveis duvidas pendentes acerca do assunto, ainda mais que se conclui com a temática mais vivida por todos e pelo mundo no ano 2020, a pandemia do (Covid-19). A análise visa de orientar os usuários deficientes do SUS, sobre seus direitos, deveres, e as políticas existentes capazes de gerar seu bem-estar na sociedade, vivendo como cidadãos com direito igualitário aos demais.

Descritores de Saúde: Saúde Pública; Rede de Atenção do SUS; Politicas, Planejamento e Administração em Saúde; Pessoas com Deficiência; Covid-19.
GESTÃO DE ESTOQUE EM TEMPOS DE PANDEMIA DA COVID-19
Authors: Oliveira Silva Matheus , Moura Santos Robson , Da Silva Anjo José Edemir 
Published: July 2022

O presente trabalho centra em discussões, a respeito da gestão de estoque no contexto pandêmico da covid-19, tendo como foco o setor farmacêutico. Diante desse cenário, surgiu o seguinte questionamento: como as farmácias se adaptaram quanto aos impactos impostos pela pandemia na sua gestão de estoque? A pesquisa teve como objetivo principal compreender e descrever as estratégias adotadas por uma farmácia localizada no município de Pio IX-PI. As informações apresentadas são decorrentes de dados empíricos, que foram analisadas por meio da abordagem de natureza qualitativa e análise interpretativa. Com a pandemia instaurada, o setor farmacêutico sofreu uma grande demanda de suprimentos essenciais para a contenção do vírus e com a falta de produtos no estoque. O estudo de caso ilustra como a farmácia IX se adaptou aos impactos impostos pela pandemia na sua gestão de estoque. O estudo destacou a relevância da gestão de estoque em tempos de crises econômica, social e sanitária.