bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trends of antihypertensive, antidiabetic, and non-steroidal anti-inflammatory drugs use among the Health Workers Cohort Study, Mexico 2004 to 2018
Authors: Ortega-Montiel Janinne , Montoya Alejandra , Soria-Saucedo René , Gallegos-Carrillo Katia , Ramírez-Palacios Paula , Salmerón Jorge , Salazar-Martinez Eduardo 
Published: June 2022

Abstract
BackgroundHypertension and Type 2 Diabetes are the most prevalent non-communicable diseases in Mexico and worldwide. The principal management therapy for these diseases is daily oral medication according to international practice management guidelines. We aim to describe the trends of the utilization of antihypertensive, antidiabetic, and non-steroidal anti-inflammatories drugs among Mexican adult population from 2004-2018 through three waves. MethodsWe conducted a longitudinal analysis using data from the Health Workers Cohort Study (HWCS), males and females, aged > 18 years. The prevalence of chronic diseases and utilization for every kind of antihypertensive, antidiabetic, and NSAIDs (measured by self-reported utilization) available, were calculated in each of the three study waves, and trends were analyzed using Fisher’s exact test. ResultsHypertension prevalence increased from 19.8 to 30.3%, same as Diabetes prevalence from 7.0 to 12.8% through fourteen years of follow up. The proportion of patients using beta-blockers and ARB II increased, same as the self-reported of combined therapy. A complete change in initiating treatment for T2D was observed since the second wave with metformin prevalence utilization of 83.9%. The utilization of common NSAIDs, mainly for muscular pain, remained around 13 to 16%. ConclusionsOur findings showed markedly changing utilization drugs prevalence for hypertension and type 2 diabetes between 2004 and 2018, and consistent utilization of NSAIDs (acetaminophen mainly) in adult Mexican population.
Prediction of HIV-1 Protease Cleavage Site from Octapeptide Sequence Information using Selected Classifiers and Hybrid Descriptors
Authors: Onah Emmanuel , Uzor Philip F , Ugwoke Ikenna Calvin , Eze Jude Uche , Ugwuanyi Sunday Tochukwu , Chukwudi Ifeanyi Richard , Ibezim Akachukwu 
Published: June 2022

Abstract
Background: In most parts of the world, especially in underdeveloped countries, Acquired Immunodeficiency Syndrome (AIDS) still remains a major cause of death, disability and unfavorable economic outcomes. This has necessitated intensive research to develop effective therapeutic agents for the treatment of Human Immunodeficiency Virus (HIV) infection, which is responsible for AIDS. Peptide cleavage by HIV-1 protease is an essential step in the replication of HIV-1. Thus, correct and timely prediction of the cleavage site of HIV-1 protease can significantly speed up and optimize the drug discovery process of novel HIV-1 protease inhibitors. In this work, we built and compared the performance of selected machine learning models for the prediction of HIV-1 protease cleavage site utilizing a hybrid of octapeptide sequence information comprising bond composition, amino acid binary profile (AABP), and physicochemical properties as numerical descriptors serving as input variables for some selected machine learning algorithms. Our work differs from antecedent studies exploring the same subject in the combination of octapeptide descriptors and method used. Instead of using various subsets of the dataset for training and testing the models, we combined the dataset and thereafter used a "stratified" ten-fold cross-validation technique for training and testing of the models.Results: Findings from this study show that logistic regression (AUC 0.97, F1 score 0.934 and balanced accuracy 87.2 %), and multi-layer perceptron classifier (AUC 0.97, F1 score 0.907 and balanced accuracy 87.4 %) have close predictive performance to the state-of-the-art model, linear support vector machine (AUC 0.97, F1 score 0.915 and balanced accuracy 90.0 %). Linear discriminant analysis, gradient boosting classifier, and Naive Bayes classifier also have good predictive performances (AUC 0.95 - 0.96, F1 score 0.919 - 0.931 and balanced accuracy 82.0 % - 85.7 %).Conclusions: Logistic regression and multi-layer perceptron classifiers have comparable predictive performances to the state-of-the-art model when octapeptide sequence descriptors consisting of AABP, bond composition and standard physicochemical properties are used as input variables. In our future work, we hope to develop a standalone software for HIV-1 protease cleavage site prediction utilizing the linear regression algorithm and the aforementioned octapeptide sequence descriptors.
ERα K303R mutation reorganizes its binding to FoxA1 regions and induces chromatin opening.
Authors: Nakadai Tomoyoshi , Yang Liying , Kumegawa Kohei , Maruyama Reo 
Published: June 2022

Abstract
I. Background: Estrogen receptor alpha (ERα) is a frequently mutated gene in breast cancer (BC). While many studies have investigated molecular dysregulation by hotspot mutations at Y537 and D538, which exhibit an estrogen-independent constitutively active phenotype, the functional abnormalities of other mutations remain obscure. The K303R mutation in primary invasive BC has been implicated with endocrine resistance, tumor size, and lymph node positivity. However, the impact of the K303R mutation on the cell epigenome is yet unknown. II. Methods and Results: We introduced the K303R ERa mutant in ERa-negative MDA-MB-453 cells to monitor ERa-dependent transactivation and to perform epigenomic analyses. The combination of ATAC-seq and ChIP-seq analyses indicated that both wild-type (WT) and the K303R mutant associated with Fox motif region at similar rates, even without an ERa-binding sequence, but only the K303R mutant induced chromatin opening at those regions. Biochemical analyses demonstrated that the WT and the K303R mutant forms of ERa can be tethered by Fox indirectly, but only the Fox/K303R/DNA complex can induce associations with the nuclear receptor cofactor NCOA2. III. Conclusions: These findings suggest that the K303R mutant induces chromatin opening at the Fox binding region through associations with NCOA2 and then probably disrupts regulation of Fox-target genes, resulting in K303R-related BC events.
Mortality and its determinants after an outbreak of post COVID-19 associated Rhino - Orbito - Cerebral mucormycosis in India
Authors: Nagarkar Nitin M , Sahu Vijaya , Arora Ripudaman , Pathak Madhumallika , Shambharkar Martina S , Naveen Prithvi 
Published: June 2022

Abstract
AIM: To report cumulative mortality rates using survival analysis from an outbreak of 211 patients with post COVID-19 rhino-orbito-cerebral mucormycosis (ROCM) in central India.METHODS: Case files of eligible patients were evaluated and mucor was identified from deep nasal swabs using freshly prepared KOH mount. All patients underwent contrast enhanced MRI and disease staging was done based on the extent of anatomical involvement. All patients received intravenous Amphotericin B and sinus debridement was done when possible. Orbital exenteration was reserved for patients with advanced orbital disease.RESULTS: The mean age was 50.7+10.2 of which 147 (70%) were men. At presentation, ROCM was limited to sinuses in 72 (34%), orbital extension was seen in 102 (48%) and 31 (15%) had CNS extension. Sinus debridement was possible in 82% cases (n=173). Thirty-five (16.6%) patients died due to ROCM. The mean follow-up of patients who survived was 126.6+16.4 days. The cumulative mortality rate at day 10 was 4.8% (95%CI=2.6 – 8.8%) and increased 13.1% (95%CI=9.1 – 18.7%) at day 30 and to 18.4% (95%CI=13.6 – 24.8%) at day 60. Majority of deaths (n=26, 75%) occurred within 1-month of ROCM presentation. Multivariable hazards analysis showed that patients with CNS involvement had a 6.5 times higher risk of death (Hazard Ratio =6.71, 95% CI=2.9 – 15.5, p<0.001). CONCLUSION: We report significantly lower mortality rates compared to recent literature that varies from 30 to 80% at 1-month follow up. Timely sinus debridement and systemic Amphotericin B can help reduce mortality. Presence of CNS extension significantly increased the mortality risk with patients with ROCM.
The Future Scenario of an Iconic Tree From the Brazilian Cerrado: Perspectives on Eremanthus﻿ Less. (Asteraceae) Conservation
Authors: ALVES FÁBIO VITALINO SANTOS , LOEUILLE BENOIT FRANCIS PATRICE 
Published: June 2022

Abstract
Characterized as one of the largest biodiversity hotspots, the Cerrado ecoregion houses a wide variety of endemic species. Several threats, such as agricultural expansion and habitat fragmentation, put the species of the Cerrado ecosystems and biodiversity at risk. The genus Eremanthus is frequent in the Cerrado and suffers from intense anthropogenic pressure due to overexploitation mainly for the construction of fences and extraction of essential oil. Environmental suitability, of the Mid-Holocene, present and future (2070), were estimated for the genus in order to characterize the importance of the climate in the species distribution and to analyse the conservation status. The Species Distribution Modelling showed that most species of Eremanthus presented similarities between the environmental suitability of the present and the Mid-Holocene, enabling the identification of areas of environmental stability in OSL areas of campos rupestres. The species of the genus were classified as Endangered and Vulnerable according to IUCN criteria, presenting very reduced areas of environmental suitability projected in the future and a low percentage of species in Protected Areas, that may influence possible extinctions of species in the genus. The approaches in this study provide consistent subsidies to assist in conservation planning.
RNA profiling of circulating tumor cells systemically captured from diagnostic leukapheresis products in prostate cancer patients
Authors: Dong Liang , Du Xinxing , Lu Changxue , Zhang Zhongyuan , Huang Chung-Ying , Yang Lei , Warren Sarah , Kuczler Morgan D. , Reyes Diane K. , Luo Jun , Amend Sarah R. , Xue Wei , Pienta Kenneth J. 
Published: June 2022

Abstract
Background: The application of circulating tumor cells (CTCs) in both clinical practice and research has been continuously limited by the rare number of targets that can be found in a tube of peripheral blood. Methods: Diagnostic leukapheresis (DLA) was used to increase the sampling volume. AdnaTest was used to process the whole leukopak, and the RNAs of captured CTCs was then profiled by NanoString nCounter platform. Spike-in experiments and leukopaks from patients with metastatic prostate cancer were used to validate this new strategy. Results: The whole leukopak was further concentrated five times to reduce the total volume from 150 mL to 30 mL, which enabled it to be processed by 3 separate AdnaTest kits. The spike-in experiment demonstrated a reliable capture when there were more than 100 cancer cells/10 mL of concentrated leukopak. In 1 out of 5 real patient samples, CTCs were only detected in the leukopak, but not in peripheral blood. The RNA profiling of DLA CTCs indicated a more aggressive phenotype of CTCs occurred when the patient was experiencing a disease relapse, even when the serum prostate specific antigen (PSA) level was still relatively low and CTCs in peripheral blood were not detectable. Conclusion: We established a new protocol, integrating DLA, AdnaTest and NanoString nCounter technology, to profile RNAs from CTCs captured from a large blood screening volume. The new protocol can process the whole leukopak with sensitive CTC capture. The RNA profiling of CTCs can provide valuable information for disease monitoring.
Development of a TLR7/8 agonist adjuvant formulation to overcome early life hyporesponsiveness to DTaP vaccination
Authors: Dowling David , Barman Soumik , Smith Alyson J. , Borriello Francesco , Chaney Danielle , Brightman Spencer E. , Malhem Gandolina , Brook Byron , Menon Manisha , Soni Dheeraj , Schüller Simone , Siram Karthik , Nanishi Etsuro , Bazin Hélène G. , Burkhart David J. , Levy Ofer , Evans Jay T. 
Published: June 2022

Abstract
Infection is the most common cause of mortality early in life, yet the broad potential of immunization is not fully realized in this vulnerable population. Most vaccines are administered during infancy and childhood, but in some cases the full benefit of vaccination is not realized in-part. New adjuvants are cardinal to further optimize current immunization approaches for early life. However, only a few classes of adjuvants are presently incorporated in vaccines approved for human use. Recent advances in the discovery and delivery of Toll-like receptor (TLR) agonist adjuvants have provided a new toolbox for vaccinologists. Prominent among these candidate adjuvants are synthetic small molecule TLR7/8 agonists. The development of an effective infant Bordetella pertussis vaccine is urgently required because of the resurgence of pertussis in many countries, contemporaneous to the switch from whole cell to acellular vaccines. In this context, TLR7/8 adjuvant (TLR7/8A) based vaccine formulation strategies may be a promising tool to enhance and accelerate early life immunity by acellular B. pertussis vaccines. In the present study, we optimized a) the formulation delivery system, b) structure, and c) immunologic activity of novel small molecule imidazoquinoline TLR7/8As towards human infant leukocytes, including dendritic cells. Upon immunization of neonatal mice, this TLR7/8A overcame neonatal hyporesponsiveness to acellular pertussis vaccination by driving a T helper (Th)1/Th17 biased T cell- and IgG2c-skewed humoral response to a licensed acellular vaccine (DTaP). This potent immunization strategy may represent a new paradigm for effective immunization against pertussis and other pathogens in early life.
Sustenance of marginal and small farm households in an advanced agricultural economy: A case of Indian Punjab
Authors: Saini Rohit , Kaur Manjeet 
Published: June 2022

Abstract

The sustainability of marginal and small farm households is a pertinent question given that their number is on the rise in South-Asia. The study aims to assess their present socio-economic profile and the challenges faced in order to draw roadmap of development for the underprivileged households. The study pertains to Indian Punjab and data from Situation Assessment Survey of 70th Round of NSSO are used. The concepts of economic surplus, occupational diversity, farm productivity, vertical and horizontal inequalities are used to achieve the objectives. This study reveals that marginal farm households faced food insecurity as they failed to meet the consumption expenditure from the income earned. Even the small farm households are left with a small surplus after meeting consumption needs. Income is unevenly distributed among farm households, with the value of the Gini coefficient being 0.48. The majority of the marginal and small farm households fall in lower-income quintiles and are occupationally more diversified than their larger counterparts. Horizontal inequalities are lower between the farm-size categories (0.14) than within farm-size categories (0.27). The Gini coefficient within each farm-size category is the highest among marginal farm households (0.50), followed by small farm households (0.45), highlighting their economic stress and tug-of-war survival. Further, the farm households belonging to socially lower castes falls only in the marginal farm-size category and represent the lowest income. Development must be sustainable and inclusive, hence, policies to develop marginal farmers centric farming systems and high value crops such as potato, cotton, sugarcane and oilseeds; providing high yielding livestock breeds; value addition through farmer-producer organizations; non-farm employment through MGNREGA; provision of institutional credit at subsidised rate of interest and; quality health and education facilities in the public sector are recommended to uplift the affected households.
Risk and damage-based optimal design of storm sewer networks using rational and fully dynamic methods, a case study (Tehran region 2)
Authors: Sadeghi Sonia , Samani Jamal Mohammad Vali , Samani Hossein Mohammad Vali 
Published: June 2022

Abstract
In this study, the risk analysis is used to determine the return period in which the design cost plus the damage risk cost is minimum. The damage includes the roads and traffic, the lawn areas, and the residential and commercial buildings. The traffic damage is based on two factors, time of delay and social negative impacts. The nonlinear reservoir model is used to convert the rainfall into runoff and the dynamic wave model is utilized to perform the network hydraulic simulation in stormwater management model (SWMM) software. This model is defined as an appropriate model. This model was applied in the risk analysis of a region in Tehran to obtain the optimal return period design. The results indicated that the optimal return period is 10 years. The rational method was also applied to the same region and same return period, but the total design cost of the rational method was greater by 5%. The damage due to the traffic include financial damages due to delays and loss of fuel resources in addition to the dissatisfaction of people due to the psychological burden.
Exploring the Latent Mechanism of Huanglian Jiedu Decoction Formula
for Anti-atopic Dermatitis by Systems Pharmacology
Authors: Xia Zhelin , Chen Guirong , Xu Yubin , Liu Chang , Shu Sheng 
Published: June 2022

Background:
Atopic dermatitis (AD) is a chronic inflammatory skin disease, which
does not have a specific drug presently. Huanglian jiedu decoction (HJD) is one of the effective
traditional Chinese medicine prescriptions. The real material and mechanisms of HJD for AD are
not clear.

Objective:
Network pharmacology and in vivo experiments were used to explore the real material
and mechanisms of HJD for AD.

Methods:
A systems’ pharmacology approach that provides a comprehensive analysis of bioactive
compounds, targets, and pathway interactions was employed to elucidate the molecular pathogenesis
of HJD for AD. First, the compound databases were constructed for HJD, and compound targets
were predicted. Then, the hub targets of HJD were selected by degree centrality analysis and validated
using the molecular docking method. Finally, Compound-Target and Target-Pathway networks
were constructed to explore the latent mechanism of HJD for AD. Then, animal models of
AD were established, the pathology of the skin lesions was observed, and RT-PCR and ELISA
methods were used to verify the key targets in the serum of AD mice.

Results:
The results showed that 60 bioactive compounds (palmatine, wogonin, cavidine, etc.) of
HJD interacting with 169 related hub targets (PTGS2, HSP90AA1, etc.) were authenticated. HJD
potentially participates in response to stimuli, biological regulation, and reproduction through the
PI3K-Akt signaling pathway, MAPK signaling pathway, Ras signaling pathway, and Fc epsilon RI
signaling pathway, which are interrelated to the pathogenesis of AD. Compared with the control
group, the thickening of the epidermis in the model group was obvious with inflammatory cells infiltrating,
the levels of PI3K, AKT, JNK, ERK, IL-4 and TNF-α were up-regulated; and 6.4g/kg
and 12.8g/kg HJD could significantly reduce the thickening of the epidermis and infiltration of inflammatory
cells, down-regulate the levels of PI3K, AKT, JNK, ERK, IL-4 and TNF-α in the AD
mice. HJD might exert its anti-AD effects by downregulating key indicators (PI3K, AKT, JNK,
ERK, IL-4, and TNF-α) in the PI3K/AKT and MAPK pathways.

Conclusions:
Our study could help us understand the compound and mechanism of HJD for AD.
Moreover, it had a guidance function to change the traditional arrangement of formula for HJD.
Identification of Human Protein Subcellular Location with Multiple Networks
Authors: Chen Lei , Wang Rui 
Published: June 2022

Background:Protein function is closely related to its location within the cell. Determination of protein subcellular location is helpful in uncovering its functions. However, traditional biological experiments to determine the subcellular location are of high cost and low efficiency, which cannot meet today’s needs. In recent years, many computational models have been set up to identify the subcellular location of proteins. Most models use features derived from protein sequences. Recently, features extracted from the protein-protein interaction (PPI) network have become popular in studying various protein-related problems.Objective:A novel model with features derived from multiple PPI networks was proposed to predict protein subcellular location.Methods:Protein features were obtained by a newly designed network embedding algorithm, Mnode2vec, which is a generalized version of the classic Node2vec algorithm. Two classic classification algorithms: support vector machine and random forest, were employed to build the model.Results:Such model provided good performance and was superior to the model with features extracted by Node2vec. Also, this model outperformed some classic models. Furthermore, Mnode2vec was found to produce powerful features when the path length was small.Conclusion:The proposed model can be a powerful tool to determine protein subcellular location, and Mnode2vec can efficiently extract informative features from multiple networks.
Transition Metal-catalyzed Regioselective Direct C-H Arylations Using
Quinone Diazide as Arylating Agent: A Mini Review
Authors: Das Partha Pratim , Das Debapratim 
Published: June 2022

Abstract:
Quinone diazides are a class of diazo compounds, having a planar six-membered ring system with diazo, carbonyl and al-kene groups in conjugation. Earlier it was used in optical, electronic, polymer materials etc. In the last few years, various rearrangements reactions and insertion reactions were explored by these diazo compounds via the formation of metallo-carbenoids. Recently, it has been used to incorporate phenol moieties to hydrocarbons or arene/heteroarenes systems via transition metal-catalyzed C-H bond activation. The reactions proceed via C-H bond insertion or migratory insertion of metal-carbenes. In many cases, the site-selectivities were obtained by the guidance of various directing groups (remova-ble or non-removable). At the same time, several asymmetric approaches were also studied to incorporate phenol deriv-atives to arenes/heteroarenes furnishing compounds showing axial chirality with high stereoselectivity. In this review, we will mainly focus on directed regioselective arylation with quinone diazides under transition metal catalysis through C-H bond activation.