bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural Modeling of Drosophila melanogaster Gut Cytochrome P450s and Docking
Comparison of Fruit Fly Gut and Human Cytochrome P450s
Authors: Nirusimhan Vijay , Andrew Gideon Daniel , Parashar Abhinav , Jeyachandran Sangavi , Jeyaraman Jeyakanthan , Subbaraj Gowthamkumar , Kulanthaivel Langeswaran 
Published: May 2022

Abstract:
Drosophila melanogaster is a prominent organism in developmental biology research and in studies related
to pathophysiological conditions like cancer and Alzheimer’s disease. The fruit fly gut contains several cytochrome
P450s (CYP450s), which have central roles in Drosophila development and in the normal physiology of the
gut. Since the crystal structures of these proteins have not been deciphered yet, we modeled the structure of 29 different
D. melanogaster gut CYP450s using Prime (Schrödinger). The sequences of chosen D. melanogaster gut
CYP450s were compared with that of their human counterparts. The common gut (and liver) microsomal CYP450s
in humans were chosen for structural comparison to find the homology and identity % of D. melanogaster CYPs
with that of their human counterparts. The modeled structures were validated using PROCHECK and the best fit
models were used for docking several known human pharmacological agents/drugs to the modeled D. melanogaster
gut CYP450s. Based on the binding affinities (ΔG values) of the selected drug molecules with the modeled fly gut
CYPs, the plausible differences in metabolism of the prominent drugs in humans and flies were projected. The gut is
involved in the absorption of oral drugs/pharmacological agents, and hence, upregulation of intestinal CYP450 and
their reactions with endobiotics and xenobiotics is envisaged. The insights gleaned from this work can validate D.
melanogaster as a model organism for studying intestinal drug metabolism, particularly in the context of a) toxicology
of pharmacological agents to the gut cells and b) how gut P450 metabolites/products can influence gut homeostasis.
This work can help establish a platform for further in vitro investigations on how intestinal CYP450 metabolism
can influence gut health. The data from this work can be used for further in silico studies and this work can serve as a
platform for future in vitro investigations on intestinal CYP450-mediated metabolism of endo- and xeno-biotics in D.
melanogaster.
An Updated and Focused Review on Heterocyclic Inhibitors for SARSCoV and SARS-CoV-2 3CLpro
Authors: Alam Ozair , Manaithiya Ajay , Mittal Shruti , Naim Mohd. Javed , Imran Mohd. , Alshrari Ahmed Subeh , Sheikh Aadil A. , Khan Imran A. 
Published: May 2022

Background:SARS-CoV and SARS-CoV-2 are exceedingly contagious and typically result in major respiratory illnesses (acute respiratory syndrome). The public health is facing enormous challenges across all the nations due to these newly emerging pathogens. Reliable and systematic examination of SARS-CoV and COVID-19 will assist in identifying infectious persons accurately. Based on the biological, chemical, and genetic link of SARS CoV-2 towards SARS-CoV, the recurrence of different anti-SARS-CoV natural drug molecules may be beneficial in the advancement of anti-COVID-19 herbal drug molecules. Here in this review, we evaluated SAR research that has recently been published as well as molecular docking analysis of previously synthesised compounds that have been targeted against SARS-CoV and SARS-CoV-2, respectively. This investigation might assist scientists in creating novel and revolutionary molecules that could target SAR-CoV-2.Objectives:The review highlights the heterocyclic inhibitors' ability to successfully inhibit SARSCoV and SARS-CoV-2. The meticulously described structure-activity relationship of potential SARS-CoV and SARS-CoV-2 inhibiting compounds has been addressed in this review.Evidence acquisition:We conducted a thorough literature assessment employing electronic databases for scientific articles highlighting potential heterocyclic inhibitors for SARS-CoVand SARSCoV- 2, published from 2010 to 2021. We recovered 415 articles, but only 220 were involved and conversed in this manuscript. The article apprehended appropriate research considering three areas: 1) SAR activity, 2) Molecular docking, and 3) Biological activity and future prospects on SARS-CoV-2.Methods:The potential compounds with decent inhibitory activity have been discussed and reviewed along with their inhibition potential, expressed in terms of IC50 value.Results:Heterocyclic scaffolds reflect an extensive spectrum of therapeutic activity and might function as an initiating concept for the designing and discovery of potential inhibitors for SARS-CoV and SARS-CoV-2 treatment.Conclusion:The points highlighted here may prove to be a vital tool for medicinal chemists working/ investigating more potent and efficacious scaffolds in treating SARS-CoV and SARS-CoV-2.
Synthetic Approaches and Pharmacological Attributes of Benzosuberone
Skeleton
Authors: Bukhari Syed Nasir Abbas 
Published: May 2022

Background:
Benzocycloheptanone is the main structural feature of numerous famous
natural pharmacophores such as Colchicine and Theaflavins. It has gained popularity in the field
of medicinal chemistry, attributing to its broad-spectrum effect.

Objective:
Numerous research publications addressing the derivatization of the benzosuberone
molecule have been published, and their biological and pharmacological features have been extensively
addressed. Numerous derivatives have been discovered as lead compounds for the development
of novel medications. Thus, the goal of this article is to summarize and analyze all
published findings on the synthesis and biological assessment of the benzosuberone skeleton.

Methods:
All main databases including SciFinder, PubMed and google scholar were used with
appropriate keywords to select related reported literature, and further bibliography in related literature
was also used to find linked reports.

Results:
Synthetic routes to benzosuberone-based ring systems were identified from the literature
and explained stepwise and after this, pharmacological activities of all benzosuberone derivatives
are listed target-wise and a detailed structure-activity relationship is developed.

Conclusion:
The current review discusses numerous synthetic approaches for the synthesis of
benzosuberone skeleton and its applications in many domains of medical chemistry. Compounds
possessing the benzosuberone skeleton play an important role in the drug development process
due to their wide range of biological actions such as anti-cancer, antibacterial, antifungal, antiinflammatory,
and so on. The results of antibacterial screening and Structure-Activity Relationship
(SAR) revealed that the compounds containing this skeleton with the piperazine and morpholine
rings have antimicrobial potential when compared to the commercial antibiotic Norfloxacin.
Despite extensive study to date, there is still room for the development of novel and efficient
pharmacophores using the structure-based drug design technique.
Current Views on Oncolytic Adenoviruses for Cancer Therapy
Authors: Bhattacharya Sankha 
Published: May 2022

Abstract:
Oncolytic viruses replicate and spread in tumors at the same time, resulting in increased cytotoxicity and the reversal of tumor immune suppression. Among other viruses, recombinant adenoviruses that replicated in tumor cells were clinically tested via intratumoral or systemic administration. Although oncolytic virus replication kills tumor cells on its own, it may also activate the immune system, which can aid in tumor control. Viruses can be modified to improve their selectivity and effectiveness. Adenovirus genomes can be easily designed to incorporate various tumor-targeting pathways and therapeutic transgenes to improve antitumor properties. Poor tumor targeting, intratumoral expansion, and virocentric immune responses are all linked to low efficacy. As a result, more effective oncolytic adenoviruses that can be used alone or in combination with chemotherapy or immunotherapy are needed. Oncolytic Adenovirus (OAds) has long been considered a potential biotherapeutic agent against various cancers due to its ability to replicate cancer cells while remaining dormant in healthy cells selectively. Several preclinical studies using genetic engineering technology have increased antitumor OAds in various cancers in recent years. Systemic OAds administration is hampered by poor targeting tropism to healthy tissues, low-level ad receptors on tumor cells, and pre-existing neutralizing antibodies. Various discoveries have been made to overcome these barriers, including stem cells, nanoparticles, polymer shielding, extracellular vesicles, hydrogels, and microparticles (MPs). These carriers may improve Oncolytic viruses’ therapeutic efficacy by improving transfection, circulatory survival, cellular interactions, specific targeting, and immune response. The structure and biology of adenoviruses, the different types of OAds, and the efficacy of different carriers in the systemic administration of OAds were all examined in this review.
Low-Carbohydrate Ketogenic Diet for Improvement of Glycemic Control:
Mechanism of Action of Ketosis and Beneficial Effects
Authors: Das Srijit , Sakr Hussein F. , Sirasanagandla Srinivasa R. , Bima Abdulhadi I. , Elsamanoudy Ayman Z. 
Published: May 2022

Abstract:
The incidence of metabolic syndrome and diabetes mellitus is increasing globally. A diet
rich in carbohydrates increases the hyperglycemic state. While considering the lifestyle changes
to combat life-threatening diseases, there is an effort to decrease the daily intake of carbohydrates.
A low-carbohydrate diet also makes the body rely more on fat for energy, so there is less fat accumulation.
A diet is considered to be low-carbohydrate ketogenic if the intake is ≤ 50 g per day. The
‘low -carbohydrate ketogenic diet’ (LCKD) produces ketosis. LCKD contains high-fat, moderateprotein,
and low-carbohydrate components. The main objectives of the present review are to discuss
insulin resistance in different viscera of the body, describe the role of adipokines in insulin resistance,
understand the mechanism of ketogenesis, and determine the impact of LCKD in overcoming
insulin resistance in the body. In the present review, we also highlight the beneficial effects
of LCKD in metabolic, neurodegenerative, cardiovascular, and lipid disorders and discuss the effect
on longevity and aging. LCKD may help in combating the morbidity and mortality arising
from the above-mentioned diseases and also help in leading a better quality of life.
Radiologic and Pathologic Findings of Axillary Intraductal Papilloma
Arising in Accessory Breast Tissue: A Case Report and Literature Review
Authors: Eun Yang Go , Bae Seong Jae 
Published: May 2022

Introduction:
This is a rare case report of axillary intraductal papilloma arising in accessory breast tissue.

Case presentation:
A 49-year-old woman presented to our clinic with a palpable right axillary mass that had first appeared 6 months earlier. Mammography and ultrasonography of right axilla revealed ovoid mass surrounding accessory breast tissue. Ultrasound-guided 14-G core-needle biopsy was performed, and pathologically revealed intraductal papilloma without atypia.

Conclusion:
If radiological finding reveal suspicious lesions in axillary breast tissue, core-needle biopsy can be performed for diagnosis because ectopic breast tissue is same spectrum of pathologic processes that occur in normal breast tissue.
Elucidating the Role of Trauma and Significant Life Stress in the Disease
of Addiction may Provide New Targets for Medication Development
Authors: Sagrera Caroline E. , Alderman Laura , Vest M. Frances , Goeders Nicholas E. , Murnane Kevin S. 
Published: May 2022

Abstract:
The role of previous life stress and trauma in addiction has been understudied and underappreciated.
To date, much previous research has emphasized other aspects of the disease of addiction,
including the reward-based neural circuitry. While previous research has offered tremendous value and
shaped human understanding of addiction, an increased emphasis on the role of stress and trauma in
addiction may provide new targets for therapeutic development. Here, we review both clinical and preclinical
literature in support of the hypothesis that addiction is largely initiated and driven by significant
previous life stressors and traumas. We describe some of the available quantitative molecular in
vitro studies, systematic literature reviews, case-control studies, and cross-sectional studies to summarize
the neurobiology of the reward pathway, the influence of stress-related hormones on the brain, and
the role of childhood trauma in the development of substance abuse. The current perspective highlights
the importance of early intervention during stressful life events for the prevention of future addiction
behavior and suggests that elucidating the neurobiology of these systems may provide new targets for
medication development for addiction.
Aging: Change in SIRT1 and Enzymatic Profile Promotes a Decrease in
the Antioxidant Capacity of Resveratrol in Human Leukocytes In Vitro
Authors: Chaves Miriam Martins , Franco Filipe Nogueira , de Cassia Cardoso Luciana , Moura Silva Bárbara Néllita , Rodrigues de Araújo Glaucy 
Published: May 2022

Background:
One of the most studied theories about aging comes from the accumulation
of free radical generation, leading to oxidative stress. Resveratrol (RSV) is a polyphenolic
compound that has been shown to act as an antioxidant in medical practice.

Objective:
To verify the antioxidant action of resveratrol (and its correlation with aging) in leukocytes
from donors of different ages, mainly through the analysis of the three main enzymes of the
antioxidant complex and the analysis of the SIRT1 signaling pathway.

Methods:
Luminol-dependent chemiluminescence assay was used to evaluate ROS and SIRT1.
Antioxidant enzymes were evaluated by commercial kits. *p<0.05.

Results:
In all age groups, there was a reduction in reactive oxygen species (ROS) in cells stimulated
with RSV. There was a positive correlation between its antioxidant effect and donor age. In
younger individuals (20-39 years old), there was an increase in catalase activity in cells exposed to
RSV. In the older groups (40-59 years old and 60-80 years old), RSV was able to increase the activity
of the enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx). Through the
analysis of SIRT1 it was possible to observe a silencing of the pathway in leukocytes treated with
RSV during aging.

Conclusion:
RSV showed antioxidant activity in all age groups, although more pronounced in
younger individuals. One of the mechanisms of action of the RSV is due to the increase in the activity
of antioxidant enzymes, which varies according to the individual's age, especially through the
modulation of important antioxidant pathways.
Factors Influencing Clinician Trust in Predictive Clinical Decision Support Systems for In-Hospital Deterioration: Qualitative Descriptive Study
Authors: Schwartz Jessica M , George Maureen , Rossetti Sarah Collins , Dykes Patricia C , Minshall Simon R , Lucas Eugene , Cato Kenrick D 
Published: May 2022

Background
Clinician trust in machine learning–based clinical decision support systems (CDSSs) for predicting in-hospital deterioration (a type of predictive CDSS) is essential for adoption. Evidence shows that clinician trust in predictive CDSSs is influenced by perceived understandability and perceived accuracy.

Objective
The aim of this study was to explore the phenomenon of clinician trust in predictive CDSSs for in-hospital deterioration by confirming and characterizing factors known to influence trust (understandability and accuracy), uncovering and describing other influencing factors, and comparing nurses’ and prescribing providers’ trust in predictive CDSSs.

Methods
We followed a qualitative descriptive methodology conducting directed deductive and inductive content analysis of interview data. Directed deductive analyses were guided by the human-computer trust conceptual framework. Semistructured interviews were conducted with nurses and prescribing providers (physicians, physician assistants, or nurse practitioners) working with a predictive CDSS at 2 hospitals in Mass General Brigham.

Results
A total of 17 clinicians were interviewed. Concepts from the human-computer trust conceptual framework—perceived understandability and perceived technical competence (ie, perceived accuracy)—were found to influence clinician trust in predictive CDSSs for in-hospital deterioration. The concordance between clinicians’ impressions of patients’ clinical status and system predictions influenced clinicians’ perceptions of system accuracy. Understandability was influenced by system explanations, both global and local, as well as training. In total, 3 additional themes emerged from the inductive analysis. The first, perceived actionability, captured the variation in clinicians’ desires for predictive CDSSs to recommend a discrete action. The second, evidence, described the importance of both macro- (scientific) and micro- (anecdotal) evidence for fostering trust. The final theme, equitability, described fairness in system predictions. The findings were largely similar between nurses and prescribing providers.

Conclusions
Although there is a perceived trade-off between machine learning–based CDSS accuracy and understandability, our findings confirm that both are important for fostering clinician trust in predictive CDSSs for in-hospital deterioration. We found that reliance on the predictive CDSS in the clinical workflow may influence clinicians’ requirements for trust. Future research should explore the impact of reliance, the optimal explanation design for enhancing understandability, and the role of perceived actionability in driving trust.
Indoor Temperatures in the 2018 Heat Wave in Quebec, Canada: Exploratory Study Using Ecobee Smart Thermostats
Authors: Oetomo Arlene , Jalali Niloofar , Costa Paula Dornhofer Paro , Morita Plinio Pelegrini 
Published: May 2022

Background
Climate change, driven by human activity, is rapidly changing our environment and posing an increased risk to human health. Local governments must adapt their cities and prepare for increased periods of extreme heat and ensure that marginalized populations do not suffer detrimental health outcomes. Heat warnings traditionally rely on outdoor temperature data which may not reflect indoor temperatures experienced by individuals. Smart thermostats could be a novel and highly scalable data source for heat wave monitoring.

Objective
The objective of this study was to explore whether smart thermostats can be used to measure indoor temperature during a heat wave and identify houses experiencing indoor temperatures above 26°C.

Methods
We used secondary data—indoor temperature data recorded by ecobee smart thermostats during the Quebec heat waves of 2018 that claimed 66 lives, outdoor temperature data from Environment Canada weather stations, and indoor temperature data from 768 Quebec households. We performed descriptive statistical analyses to compare indoor temperatures differences between air conditioned and non–air conditioned houses in Montreal, Gatineau, and surrounding areas from June 1 to August 31, 2018.

Results
There were significant differences in indoor temperature between houses with and without air conditioning on both heat wave and non–heat wave days (P<.001). Households without air conditioning consistently recorded daily temperatures above common indoor temperature standards. High indoor temperatures persisted for an average of 4 hours per day in non–air conditioned houses.

Conclusions
Our findings were consistent with current literature on building warming and heat retention during heat waves, which contribute to increased risk of heat-related illnesses. Indoor temperatures can be captured continuously using smart thermostats across a large population. When integrated with local heat health action plans, these data could be used to strengthen existing heat alert response systems and enhance emergency medical service responses.
Indirect treatment comparison of anifrolumab efficacy versus belimumab in adults with systemic lupus erythematosus
Authors: Bruce Ian N , Golam Sarowar , Steenkamp Jason , Wang Pearl , Worthington Evelyn , Desta Barnabas , Psachoulia Konstantina , Erhardt Wilma , Tummala Raj 
Published: May 2022

Aim:
Assess the comparative efficacy of anifrolumab 300 mg versus belimumab 10 mg/kg in adults with moderate-to-severe systemic lupus erythematosus (SLE) receiving standard therapy.
Patients and methods:
Population-adjusted simulated treatment comparisons (primary analyses) and matching-adjusted indirect comparisons (supporting analyses) were conducted using individual patient data from TULIP-1/TULIP-2 and summary-level data from BLISS-52/BLISS-76.
Results:
Compared with belimumab-treated patients, anifrolumab-treated patients were more than twice as likely to achieve a reduction of four or more points in SLE Disease Activity Index 2000 score (simulated treatment comparison odds ratio: 2.47; 95% CI: 1.16–5.25) and SLE Responder Index-4 response (odds ratio: 2.61; 95% CI: 1.22–5.58) at 52 weeks.
Conclusion:
Patients with moderate-to-severe SLE are more likely to achieve an improvement in disease activity with anifrolumab than with belimumab.
Party System Change in Québec: Evidence from Recent Elections
Authors: Allan James P. , Vengroff Richard 
Published: May 2022

Since the 1990s, provincial elections in Québec have signaled an incremental change in Québec’s party system. These changes are manifested in increasing voter dealignment and volatility in party support. In this article we find that these trends largely continued in both the election of 2012, which produced a minority government and in the 2014 election that resulted in a majority government. Taking a longer--‐term perspective, we examine changes in public opinion, party identification, electoral volatility, and voting behavior in Québec Provincial elections since 1998. The implications for future government formation and the potential impact on policy are examined.
Analytical representations of the Residence Time Distribution associated with hyporheic exchange beneath dune-like bedforms for different normalized sediment bed depths and groundwater underflow velocities.
Authors: Monofy Ahmed , Boano Fulvio , Grant Stanley 
Published: May 2022

The hyporheic exchange below dune-shaped bedforms has a great impact on
the stream environment. One of the most important properties of the
hyporheic zone is the residence time distribution (RTD) of flow paths in
the sediment domain. Here, we evaluate the influence of dimensionless
sediment depths d b * = 2 π d b / λ where λ is the dune wavelength and
different values of dimensionless groundwater underflow values u b *
(similar to dune migration celerity), on the shape of the hyporheic
exchange RTD. Empirical RTDs were generated, over a range of
combinations between d b * and u b * values, from numerical
particle tracking experiments in which 10000 particles were released
over a flat domain. These empirical RTDs are represented by different
distributions over the range of d b * and u b * . A Fréchet RTD is
the best fit for deep beds ( d b * >3.2) and negligible
underglow ( u b * <0.1). A LogNormal RTD is often the best
representation for u b * ≤ 0 . 8 , while a Gamma RTD performs better for
larger values of u b * . In general, a LogNormal RTD provides a good
representation of the empirical RTDs in all cases, as it is identified
as either the best or the second-best fitting distribution according to
the Anderson-Darling test. The parameters of these analytical
distributions vary with d b * and u b * , and this dependence is
graphically represented in this work. These results contribute to our
understanding of the physical and mixing processes underpinning
hyporheic exchange in streams and paves the way for a quick evaluation
of its potential impact on nutrient and contaminant processing (e.g.,
based on the magnitude of the Damköhler number).