bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeted Immuno-Antiretroviral HIV Therapeutic Approach to Provide Dual Protection and Boosts Cellular Immunity: A Proof-of-Concept Study
Authors: Mandal Subhra , Sunagawa Shawnalyn , Prathipati Pavan Kumar , Belshan Michael , Shibata Annemarie , Destache Christopher 
Published: November 2020

Abstract
Background: Human immunodeficiency virus (HIV)-infected active and latent C-C motif chemokine receptor-5 (CCR5) expressing long-lived T-cells are the primary barrier to HIV/AIDS eradication. Broadly neutralizing antibodies and latency-reversing agents are the two most promising strategies emerging to achieve ‘functional cure’ against HIV infection. Antiretrovirals (ARVs) have shown to suppress plasma viral loads to non- detectable levels and other strategies have demonstrated a ‘functional cure’ against HIV infection is achievable. Strategies are effective at inducing direct or immune-mediated cell death of latent HIV+ T-cells but have shown respective limitations. We designed a novel targeted ARVs-loaded nanoformulation that combines a CCR5 monoclonal antibody and antiretroviral drugs (ARV) as a dual protection strategy to promote HIV ‘functional cure’. The modified CCR5 monoclonal antibody (xfR5 mAb) surface-coated dolutegravir (DTG) and tenofovir alafenamide (TAF) loaded nanoformulation (xfR5-D+T NPs)Results: The nanoformulation was uniformly sized <250 nm, with 6.5 times enhanced antigen-binding affinity compared to naïve xfR5 mAb, and provided prolonged DTG and TAF intracellular retention. The multivalent and sustained drug release properties of xfR5-D+T NPs enhance the protective efficiency against HIV by approximately 12, 3, and 5 times compared to naïve xfR5 mAb, D+T NP alone, and xfR5 NPs, respectively. Further, the nanoformulation demonstrated high binding-affinity to CCR5 expressing CD4+ cells, monocytes, and other HIV prone/latent T-cells by 25, 2, and 2 times, respectively. Finally, during short-term pre-exposure prophylaxis, the xfR5-D+T NPs induced a protective immunophenotype, with boosted T-helper (Th), temporary memory (TM), and effector (E) sub-population. Treatment with xfR5-D+T NPs to HIV-infected T-cells induced a defensive/activated immunophenotype with boosted naïve, Th, central memory, TM, EM, E, and activated cytotoxic T-cells population.Conclusion: This dual-action targeted nanoformulation could potentially become a multifactorial solution to achieve a “functional cure.”
A Pre-Training Technique to Localize Medical BERT and to Enhance Biomedical BERT
Authors: Wada Shoya , Takeda Toshihiro , Manabe Shiro , Konishi Shozo , Kamohara Jun , Matsumura Yasushi 
Published: November 2020

Abstract
Background: Pre-training large-scale neural language models on raw texts has been shown to make a significant contribution to a strategy for transfer learning in natural language processing (NLP). With the introduction of transformer-based language models, such as Bidirectional Encoder Representations from Transformers (BERT), the performance of information extraction from free text by NLP has significantly improved for both the general domain and the medical domain; however, it is difficult for languages in which there are few publicly available medical databases with a high quality and a large size to train medical BERT models that perform well.Method: We introduce a method to train a BERT model using a small medical corpus both in English and in Japanese. Our proposed method consists of two interventions: simultaneous pre-training, which is intended to encourage masked language modeling and next-sentence prediction on the small medical corpus, and amplified vocabulary, which helps with suiting the small corpus when building the customized corpus by byte-pair encoding. Moreover, we used whole PubMed abstracts and developed a high-performance BERT model, Bidirectional Encoder Representations from Transformers for Biomedical Text Mining by Osaka University (ouBioBERT), in English via our method. We then evaluated the performance of our BERT models and publicly available baselines and compared them.Results: We confirmed that our Japanese medical BERT outperforms conventional baselines and the other BERT models in terms of the medical-document classification task and that our English BERT pre-trained using both the general and medical domain corpora performs sufficiently for practical use in terms of the biomedical language understanding evaluation (BLUE) benchmark. Moreover, ouBioBERT shows that the total score of the BLUE benchmark is 1.1 points above that of BioBERT and 0.3 points above that of the ablation model trained without our proposed method.Conclusions: Our proposed method makes it feasible to construct a practical medical BERT model in both Japanese and English, and it has a potential to produce higher performing models for biomedical shared tasks.
m6a Methylation Inhibition by Cycloleucine Impaired Porcine Oocyte Meiosis and Early Embryonic Development via Remodeling Histone Modifications and Altering Metabolism Related Gene Expression in Blastocysts
Authors: Zhang Meng , Zhang Sheng , Zhai Yanhui , Han Yu , Huang Rong , An Xinglan , Dai Xiangpeng , Li Ziyi 
Published: November 2020

Abstract
BackgroundOocytes maturation and early embryo development were regulated precisely by a series of factors at transcriptional and posttranslational levels. N6-methyladenosine (m6A) is the most prevalent modification in mRNA as a crucial regulator in RNA metabolism and gene regulation. However, the role of m6A on porcine oocyte maturation and early embryogenesis is largely unknown. ResultsHere, we found that oocytes treated with cycloleucine (CL), an inhibitor of m6A, could impair cumulus expansion, elevate mitochondrial reactive oxygen species (ROS) concentration and decreased oocytes maturation which partially caused by disturbed spindle organization and chromosomes alignment. Moreover, our results indicated that the CL treated parthenogenetic embryos arrested at 4-cell stage and showed worse blastocyst quality. CL treatment not only decreased the methylation levels of nucleic acid, H3K4me3 and H3K9me3, while increased the acetylation level of H4K16 during parthenogenetic embryos development in pigs. Furthermore, single cell RNA-seq (scRNA-seq) analysis indicated that CL treatment dramatically elevated the expression of metabolism-related (SLC16A1 and MAIG3 etc.) and maternal related (BTG4, WEE2 and BMP15 etc.) genes at blastocyst stage. ConclusionsTaken together, we found that m6A methylation inhibition by CL impaired porcine oocyte meiosis and early embryonic development via remodeling histone modifications and altering metabolism related gene expression in blastocysts.
Identification of the Role of SOX2 During Early Embryogenesis in Pigs
Authors: Lee Mingyun , Oh Jong-Nam , Kim Seung-Hun , Choi Kwang-Hwan , Lee Dong-Kyung , Choe Gyung Cheol , Jeong Jinsol , Lee Chang-Kyu 
Published: November 2020

Abstract
BackgroundThe lineage specification of mammalian embryos during preimplantation development has been studied for a long time but is still unclear. To understand the developmental process, many studies have examined lineage markers and mechanisms focusing on mouse embryos, but there are differences from human embryos. Pigs have been studied extensively in the field of disease model animals and xenotransplantation because of their physiological similarity with humans. Therefore, it is necessary to analyze gene expression patterns and lineage specification markers during early embryogenesis in pigs, a model animal similar to humans.ResultsAnalysis of the expression pattern of the core pluripotent factors (OCT4, SOX2 and NANOG) of preimplantation porcine embryos showed that SOX2 was only expressed in some cells from the early stage, so SOX2 was selected as an ICM inducible factor candidate. Next, transcript and protein expression patterns were estimated at the early stage (Day 5) and late stage (Day 7) of blastocysts injected with the CRISPR Cas9 system selected through gRNA validation. An ICC assay revealed that the expression of ICM-related genes (SOX2, NANOG and SOX17), except OCT4, was suppressed, and the total cell number was also decreased. Likewise, according to real-time PCR analysis, pluripotency-related genes (NANOG, SOX17 and SMAD7), excluding OCT4, and proliferation-related genes (KDM8 and DDB1) were decreased in SOX2-targeted blastocysts, which showed more differences in late-stage blastocyst than in early-stage blastocyst. Last, in SOX2-overexpressing embryos, the total blastocyst cell number was greatly increased, but the ICM/TE ratio decreased.Conclusions﻿Taken together, our results demonstrated SOX2 is essential for ICM formation and cell proliferation in porcine early stage embryogenesis. These findings will help to elucidate gene regulation related to lineage specification during porcine early development.
Boswellic acid and myrrh sesquiterpene alleviate hypoxic-ischemic brain injury via regulating TLR4/NF-κB and Ang Ⅰ/Ang Ⅱ/Tie signaling pathway on MCAO rats
Authors: Miao Xiaodong , Zhao Zizhang , Xu Zhuo , Su Shulan , Jiang Baoping , Shang Er-xin , Li Jiashang , Zhu Yue , Guo Jianming , Yu Li , Qian Dawei , Duan Jin-ao 
Published: November 2020

Abstract
Background: The frankincense and myrrh can be used in traditional Chinese medicine (TCM) clinic with the treatment of stroke, while its mechanism is still unclear. The aim of this study was to investigate the effects of boswellic acid (BA) and myrrh sesquiterpene (MS) compositions on ischemic stroke in rats. Methods: The ischemic stroke rat model induced by ischemia-reperfusion (I/R) after transient middle cerebral artery occlusion (MCAO) was adopted and treated with boswellic acid and myrrh sesquiterpenes with proportions compatibility (BA-MS) of 10:1, 5:1 and 20:1. Biochemical indexes, histopathological analysis, metabolomics analysis of plasma and urine, as well as 16S rDNA sequencing of gut microbiota and short chain fatty acids were investigated. Results: BA and MS could obviously significantly ameliorated neurological deficits scores, reduced cerebral infarction area in I/R, and improve the damage of brains and lungs of MCAO rats. Additionally, it could significantly reduce the expression of neuroinflammatory factors (IL-1β, nNOS, BDNF, NGF) and angiogenic growth factors (ET-1, PAI-1, PDGF, VEGF, VWF), and significantly increase the expression of nerve indicators (TDP-43, NeuN) and angiogenic growth factors (Ang Ⅱ, TGF-β1, bFGF). After the administration of BA-MS, the metabolites of ischemic stroke in plasma and urine of ischemic stroke of rats were reversed, mainly correlated with the metabolic pathway of linoleic acid metabolism (impact value =1), and the gut microbiota and SCFAs metabolism of cecal contents were also improved. Conclusions: BA-MS can improve brain injury of MCAO rats via Ang/Tie and TLR4 signaling pathway, improve metabolism disorder by regulating linoleic acid metabolism pathway, and ameliorate gut microbes and their metabolic disorders.
A Qualitative Study on The Role of Community Health Workers In Influencing Social Connectedness Using The Household Model: A Case Study of Neno District, Malawi
Authors: Ndambo Myness Stella Kasanda , Munyaneza Fabien , Aron Moses , Makungwa Henry , Michaelis Annie , Nhlema Basimenye , Connolly Emilia 
Published: November 2020

Abstract
Background: There is growing global recognition that community health workers (CHWs) play a key role in facilitating social connectedness. Through direct interactions and relationship building, CHWs link people to key services such as healthcare and social support. Several models aim to understand how CHWs facilitate these interactions, but the theory of change is not yet fully understood. In Neno District, Malawi, CHWs recently transitioned from a disease-focused model to what we call the “household model.” Under the household model, each CHW is assigned to several households to provide screening and linkage to care, as well as psychosocial and chronic disease support. We theorise that this public health approach facilitates social connectedness in the households and rural communities served by CHWs. We aim to understand drivers of influence on social connections from the CHW-, healthcare worker-, and patient perspectives. Methods: This was a cross-sectional qualitative study utilising focus group discussions (FGDs) and in-depth semi-structured interviews with purposively sampled community stakeholders, CHWs, health service providers, and patients (total N=180) from October 2018 through March 2020. Results: Participants reported improved social interactions and connectedness and increased access to health care in their communities following the transition to the household model. This was driven by factors including reduced stigma and discrimination, empowerment of households and community members, and fostering both social cohesiveness and individual agency in accessing health services. The main themes that emanated from this study are; expansion of care by CHWs, trust in CHW’s provision of care, and equal treatment of community members by CHWs. Conclusion: Our study demonstrates that through the polyvalent household model, CHWs foster high levels of social connectedness in the communities, evidenced by a reported reduction in stigma and discrimination and an increase in individual agency in accessing health services.
From time dependent incorporation of molecular building blocks to application properties for inorganic and organic three-dimensional network polymers
Authors: Keer Lies De , Kilic Karsu , Steenberge Paul Van , Daelemans Lode , Kodura Daniel , Frisch Hendrik , Clerck Karen De , Reyniers Marie-Françoise , Barner-Kowollik Christopher , Dauskardt Reinhold , D'hooge Dagmar 
Published: November 2020

Abstract
The three-dimensional configurational arrangement of natural and synthetic network materials determines their application range. Control of the real time incorporation of each building block, hence, all functional groups is desired so that we can regulate macroscopic properties from the molecular level onwards. Here we interconnect kinetic Monte Carlo simulations from the field of chemical kinetics and molecular dynamic simulations from the field of physics. We visualize for (in)organic network material synthesis how the initial building blocks interact timewise and spatially, accounting for variations in inter- and intramolecular chemical reactivity, diffusivity, segmental compositions, branch/network point locations, and defects. We use the kinetic and three-dimensional structural information to construct structure-property relationships based on molecular descriptors such as the molecular pore size or dangling chain distribution, differentiating between ideal and non-ideal structural elements. The generic nature is illustrated by constructing such relationships for the synthesis of organosilica, epoxy-amine and Diels-Alder based networks.
Temperatura e tempo de frio para a superação da dormência de gemas de videiras ‘Chardonnay’, ‘Merlot’ e ‘Cabernet Sauvignon’
Authors: Anzanello Rafael , Christo Mariane Castanho de 
Published: November 2020

A videira apresenta um período de dormência no outono/inverno, superado pelo acúmulo de horas de frio (HF) ≤7,2ºC, temperatura genérica para frutíferas temperadas. Este trabalho objetivou avaliar a eficiência de diferentes temperaturas e tempos de frio para a superação da dormência de gemas de videiras. Estacas de videiras ‘Chardonnay’, ‘Merlot’ e ‘Cabernet Sauvignon’ foram coletadas em vinhedos localizados em Veranópolis-RS, em junho/2016, após 300 horas de frio (HF≤7,2°C) a campo. Os ramos, processados em estacas de nós-isolados, foram submetidos em câmaras incubadoras a três intensidades de frio (7,2, 10 e 13°C) e seis tempos de exposição (300, 396, 492, 588, 684 e 780 HF - considerando o somatório do frio acumulado a campo e o frio imposto em condições controladas). Ao final de cada tempo de frio, uma parcela das estacas foi transferida para 25ºC para indução e avaliação da brotação das gemas. Os dados de brotação foram analisados quanto aos parâmetros de brotação máxima, precocidade e uniformidade. As cultivares apresentaram diferenças na necessidade de frio e na efetividade das temperaturas de frio para a superação da dormência. A ‘Chardonnay’ necessitou até 300 HF para a superação da dormência, independente da temperatura testada; a ‘Merlot’ necessitou até 396 HF a 7,2ºC e a 10ºC e até 492 HF a 13ºC; e o ‘Cabernet Sauvignon’ necessitou até 492 HF a 7,2ºC, até 588 HF a 10ºC e até 684 HF a 13ºC. A precocidade e uniformidade de brotação das gemas foi maior após suprido o frio na dormência para cada cultivar.
Computational Evidences of Phytochemical Mediated Disruption of PLpro Driven Replication of SARS-CoV-2: A Therapeutic Approach against COVID-19
Authors: Balkrishna Acharya , Mittal Rashmi , Arya Vedpriya 
Published: November 2020

Background:
COVID-19 caused by SARS-CoV-2 has been declared as a global pandemic
by WHO. Comprehensive analysis of this unprecedented outbreak may help to fight against the disease
and may play a pivotal role in decreasing the mortality rate linked with it. Papain-like protease
(PLpro), a multifunctional polyprotein, facilitates the replication of SARS-CoV-2 and evades it from
the host immunological response by antagonizing cytokines, interferons and may be considered as a
potential drug target to combat the current pandemic.

Methods:
Natural moieties obtained from medicinal plants were analysed for their potency to target
PLpro of SARS-CoV-2 by molecular docking study and were compared with synthetic analogs named
as remdesivir, chloroquine and favipiravir. The stability of complexes of top hits was analysed by MD
Simulation, and interaction energy was calculated. Furthermore, average RMSD values were computed
and deepsite ligand-binding pockets were predicted using Play Molecule. Drug-like-abilities of these
moieties were determined using ADMET and bond distance between the ligand and active site was assessed
to predict the strength of the interaction.

Results:
Nimbocinol (-7.6 Kcal/mol) and sage (-7.3 Kcal/mol) exhibited maximum BA against PLpro
SARS-CoV-2 as evident from molecular docking study, which was found to be even better than
remdesivir (-6.1 Kcal/mol), chloroquine (-5.3 Kcal/mol) and favipiravir (-5.7 Kcal/mol). Both nimbocinol-
PLpro and sage-PLpro SARS-CoV-2 complex exhibited stable conformation during MD Simulation
of 101ns at 310 K, and potential, kinetic and electrostatic interaction energies were computed,
which was observed to be concordant with results of molecular docking study. RMSD average values
were found to be 0.496 ± 0.015 Å and 0.598 ± 0.023 Å for nimbocinol and sage, respectively, thus revealing
that both the deviation and fluctuations during MD Simulation were observed to be least.
Deepsite prediction disclosed that both compounds occupied cryptic pockets in receptor and non-bond
distance analysis revealed the formation of hydrogen bonds during ligand-receptor interaction. ADMET
exploration further validated the drug-like properties of these compounds.

Conclusion:
Present study revealed that active constituents of Azadirachta indica and Salvia officinalis
can be potentially used to target SARS-CoV-2 by hindering its replication process.
Standardizing the Effective Correlated Dosage of Olanzapine and Empagliflozin in Female Wistar Rats
Authors: Ashraf Ghulam Md. , Alghamdi Badrah S. , Alshehri Fahad S. , Alam Mohammad Z. , Tayeb Haythum O. , Tarazi Frank I. 
Published: November 2020

Aim:
The primary aim of this study was to standardize the correlated effective dosage of
the antidiabetic drug empagliflozin (EMPA) and the antipsychotic drug olanzapine (Ola).

Background:
Atypical antipsychotics are associated with BWG and metabolic disturbances for which
many approaches have been used to minimize these issues, including antidiabetic drugs. The antidiabetic
drugs have been quite effective in reversing BWG induced by the administration of antipsychotic
drugs in patients who have psychosis, schizophrenia and bipolar disorder.

Objective:
The objective of this study was to standardize the correlated effective dosage of EMPA and
Ola.

Methods:
The study was carried out for 28 days to represent the chronic effect of Ola on female
Wistar rats. Rats were divided into three groups based on the dose they received: control (vehicle),
Ola-4 and Ola-8 (4 and 8 mg/kg/OD, respectively), and EMPA-10 and EMPA-20 (10 and 20
mg/kg/OD, respectively).

Results:
Both doses of Ola produced a significant increase in the percentage of BWG, however, Ola-4
produced a higher BWG. Also, both the doses of EMPA were able to reverse the effect of Ola-induced
BWG; however, EMPA-20 produced a higher reversal in BWG and normalized the rat's body weight.

Conclusion:
We conclude that Ola-4 and EMPA-20 were the most effective dosage for experimental
purposes in female Wistar rats. The findings of this study standardized the effective correlated dosage
of olanzapine and empagliflozin in female Wistar rats that will help understand the underlying molecular
and behavioral mechanisms.
Dipeptidyl Peptidase IV Inhibitors for Nonalcoholic Fatty Liver Disease - Systematic Review and Metanalysis
Authors: dos Santos Lucas Ribeiro , Duarte Marcio Luis , Peccin Maria Stella , Gagliardi Antônio Ricardo de Toledo , Melnik Tamara 
Published: November 2020

Introduction:
Hepatic steatosis is a frequent condition, that afflicts, especially, obese and insulin resistant
patients; diagnosis is made, usually, through imaging tests. Despite the high prevalence and risk of complications, there is
no specific treatment approved, though a vast number of medications have been tested.

Objective:
To determine the efficacy of dipeptidyl peptidase IV inhibitors (i DPP-IV) in the treatment of NAFLD.

Methods:
We searched the electronic databases of the Cochrane Library, MEDLINE, EMBASE and LILACS, as well as
reference lists of the included studies and grey literature; 9 studies were selected for inclusion.

Results:
7 studies were used for metanalysis, for 3 outcomes. i DPP-IV showed an ALT-reducing power of MD -10.83
[95% CI 35.23 to 13.57] at 3 months and MD -9.27 [95% CI 10.92 to -7.62] at 6 months of intervention, as well as
reduction of hepatic steatosis via MRI of SMD 0.10 [95% CI 0.31 to 0.50]; the overall incidence of adverse events was
very low. The studies were considered of low and very low quality by the GRADE evaluation.

Conclusion:
Because of the poor overall quality of the studies and heterogeneity of the population analyzed, i DPP-IV did
not show efficacy on inflammatory markers or fibrosis in patients with NAFLD.
Common Issues Among Asthma, Epilepsy, and Schizophrenia: From Inflammation to Ca2+/cAMP Signalling
Authors: Bergantin Leandro Bueno 
Published: November 2020

Background:
A large amount of evidence has described that asthma may be associated
with a high epilepsy risk, and epilepsy may be linked with high asthma risk, especially among children
and individuals in their 30s. Curiously, asthma has also been associated with an increased risk
for schizophrenia. Most interestingly, a bidirectional link between schizophrenia and epilepsy has
also been established and has been of interest for many years.

Objective:
Bearing in mind the experience of our group in the field of Ca2+/cAMP signalling pathways,
this article discussed, beyond inflammation, the role of these signalling pathways in this link
among epilepsy, asthma, and schizophrenia.

Methods:
Publications involving these signalling pathways, asthma, epilepsy, and schizophrenia
(alone or combined) were collected by searching PubMed and EMBASE.

Results and Conclusion:
There is a clear relationship between Ca2+ signalling, e.g. increased Ca2+
signals and inflammatory responses. In addition to Ca2+, cAMP regulates pro- and anti-inflammatory
responses. Then, beyond inflammation, the comprehension of the link among epilepsy, asthma,
and schizophrenia could improve the drug therapy.