bluuebunny/crossref_metadata_2025_split huggingface dataset:
4-Aminocoumarin Derivatives as Multifaceted Building Blocks for the Development
of Various Bioactive Fused Coumarin Heterocycles: A Brief Review
Authors: Patra Prasanta , Patra Susanta 
Published: December 2022

Abstract:
Aminocoumarins are found to be present in many natural products, pharmaceuticals,
and organic materials. These derivatives demonstrate numerous biological activities including
DNA gyrase, anti-proliferative and anti-breast cancer activities. Among the allaminocoumarin
derivatives, 4-aminocoumarin derivatives have been reported to exhibit anticancer
and anti-fungal properties. 4-Aminocoumarins and their derivatives are important precursors
for the synthesis of coumarin fused N-heterocycles. Due to the presence of an amino
group as well as enamine carbon, it is very reactive towards electrophiles and in most of the
cases, it has a higher tendency to cyclize immediately by the various reaction path ways and
provides the heterocyclic products. Unlike other aromatic amines, it did not give any Schiff
base on reaction with aldehydes or ketones. Lamellarins, ningalin A, ningalin B, schumanniophytin,
santiagonamine, goniothaline, and polyneomarline C are important natural coumarin fused N-heterocycles
and show excellent biological activities, including antitumor, reversal of multidrug resistance, anti-HIV, wound
healing, anti-malarial, anti-hepatitis, and anti-syphilis activities. The synthesized coumarin fused N-heterocycles
have been reported to display Topoisomerases I inhibitory, DYRK1A inhibitory, and anti-cancer activities. Most of
the syntheses of pyrrolo/imidazolo/indolo[3,2-c]coumarin, pyrido/quinolino[3,2-c]coumarins, pyrimidino[
c]coumarin and oxazino[c]coumarin have been synthesized easily from 4-aminocoumarin. This paper reviews
the research data in the literature on the synthesis of bioactive coumarin fused heterocycles using 4-aminocoumarin
derivatives over the period of 2-3 decades. It covers the synthetic applicability of 4-aminocoumarin for the development
of coumarin fused 5-, 6-, and 8-membered ring derivatives via classical reaction protocols, microwavemediated
reactions, organo-catalyzed reactions, transition metal-catalyzed reactions, and green reaction protocols.
Human Orphan Cytochromes P450: An Update
Authors: Molina-Ortiz Dora , Torres-Zárate Carmen , Santes-Palacios Rebeca 
Published: December 2022

Abstract:
Orphan cytochromes P450 (CYP) are enzymes whose biological functions and substrates are unknown.
However, the use of new experimental strategies has allowed obtaining more information about their relevance in the
metabolism of endogenous and exogenous compounds. Likewise, the modulation of their expression and activity has
been associated with pathogenesis and prognosis in different diseases. In this work, we review the regulatory pathways
and the possible role of orphan CYP to provide evidence that allow us to stop considering some of them as
orphan enzymes and to propose them as possible therapeutic targets in the design of new strategies for the treatment
of diseases associated with CYP-mediated metabolism.
Phage Therapy as a Protective Tool Against Pathogenic Bacteria: How Far
We Are?
Authors: Chakrabarti Alok Kumar , Singh Kushagri , Biswas Asim , Dutta Shanta 
Published: December 2022

Abstract:
Bacterial infections continue to jeopardize human and animal health, impacting millions
of lives by causing significant deaths every year. The use of antibiotics remains the primary choice
of therapy and has only been partly successful in reducing the disease burden due to the evolving
nature of resistant microbes. Widespread and inappropriate use of antibiotics resulted in the development
of antibiotic-resistant microbial species provoking substantial economic burdens. The most
promising way to resolve the issue of antibiotic resistance is the use of bacterial viruses called bacteriophages
to treat microbial infections. Earlier reports on experimental bacteriophage therapy
showed successful patient outcomes, and many clinical trials of such clinical bacteriophages have
already been investigated in many western countries. In this review, we are focusing on the advantages
as well as drawbacks of bacteriophage therapy to use it as an alternative to antibiotics for microbial
infections, together with its current success status. There is also a need to extensively study
the past, present, and future outlook of phage therapy in comparison to presently available antimicrobial
agents and especially immunological response by the host after phage administration. Our
aim is to highlight the fast-promoting field of bacteriophage therapy and provocations that lie ahead
as the world is gradually moving aside from complete dependence on antimicrobial agents.
Montelukast Inhibits Lung Cancer Cell Migration by Suppressing
Cysteinyl Leukotriene Receptor 1 Expression In vitro
Authors: Wei Shuo , Chen Yisheng , Zhang Jinye 
Published: December 2022

Background:
Lung cancer is a major threat to public health and remains difficult to treat. Repositioning of existing drugs has emerged as a therapeutic strategy in lung cancer. Clinically, low-dose montelukast has been used to treat asthma.

Objective:
We evaluated the potential of using montelukast to treat lung cancer.

Methods:
Migration was detected using wound-healing and Transwell assays, the expression of CysLT1 using western blotting, and subcellular localization of CysLT1 using immunofluorescence. CRISPR/Cas9 technology was used to further investigate the function of CysLT1.

Results:
Subcellular localization staining showed that the CysLT1 distribution varied in murine and human lung cancer cell lines. Furthermore, montelukast suppressed CysLT1 expression in lung cancer cells. The treated cells also showed weaker migration ability compared with control cells. Knockout of CysLT1 using CRISPR/Cas9 editing in A549 cells further impaired the cell migration ability

Conclusion:
Montelukast inhibits the migration of lung cancer cells by suppressing CysLT1 expression, demonstrating the potential of using CysLT1 as a therapeutic target in lung cancer.
KCa-Related Neurological Disorders: Phenotypic Spectrum and Therapeutic
Indications
Authors: Zahra Aqeela , Liu Ru , Han Wenzhe , Meng Hui , Wang Qun , Wang YunFu , Campbell Susan L. , Wu Jianping 
Published: December 2022

Abstract:
Although potassium channelopathies have been linked to a wide range of neurological con-
ditions, the underlying pathogenic mechanism is not always clear, and a systematic summary of clini-
cal manifestation is absent. Several neurological disorders have been associated with alterations of
calcium-activated potassium channels (KCa channels), such as loss- or gain-of-function mutations,
post-transcriptional modification, etc. Here, we outlined the current understanding of the molecular
and cellular properties of three subtypes of KCa channels, including big conductance KCa channels
(BK), small conductance KCa channels (SK), and the intermediate conductance KCa channels (IK).
Next, we comprehensively reviewed the loss- or gain-of-function mutations of each KCa channel and
described the corresponding mutation sites in specific diseases to broaden the phenotypic-genotypic
spectrum of KCa-related neurological disorders. Moreover, we reviewed the current pharmaceutical
strategies targeting KCa channels in KCa-related neurological disorders to provide new directions for
drug discovery in anti-seizure medication.
Immunotherapy-Associated Hypophysitis under Anti-PD1: Two Case
Reports
Authors: Ma Jing , Shen Xinyu , Yang Minglan , Xu Hua , Zhou Huan , Wang Liwei 
Published: December 2022

Background:
Immunotherapy-associated hypophysitis is an uncommon adverse event.
However, if not handled properly, it could lead to fatal sequelae.

Case Presentations:
Case 1. A 66-year-old man presented to our hospital with hyponatremia. He
had low plasma levels of adrenocorticotropin and cortisol. The patient had a history of non-small
cell lung cancer and had undergone 16 cycles of immunotherapy with sintilimab, a monoclonal
antibody against programmed cell death protein 1 (PD1). He was diagnosed with adrenal insufficiency
secondary to immunotherapy-associated hypophysitis and received a physiological dose of
glucocorticoids. Upon discharge, he has prescribed a continued course of hormone replacement
therapy combined with immunotherapy. Case 2. The second case profiled here involved a 58-
year-old patient diagnosed with gastric antrum cancer. After ten months of immunotherapy with
carrelizumab, a human high-affinity immunoglobulin G4 (IgG4) anti-PD-1 monoclonal antibody
drug, the patient was referred to the Endocrinology Department at our medical centre for adrenal
nodules and intolerance of anorexia. He also suffered from hypophysitis and was prescribed hormone
replacement therapy combined with immunotherapy.

Conclusions:
This article discusses the clinical characteristics, diagnosis, treatment, and subsequent
follow-up for immunotherapy-associated hypophysitis in the context of two case reports.
Based on our findings and observations, we conclude that patients with immunotherapy should
regularly be referred to endocrine-related follow-up during tumour treatment.
Pharmacological Activity and Mechanisms of Action of Terpenoids from
Laurus nobilis L.
Authors: Kamdem Boniface Pone , Le Doux Kamto Eutrophe , Soh Désiré , Pegnyemb Dieudonné Emmanuel , Zingue Stéphane , Paumo Hugues Kamdem , Katata-Seru Lebogang Maureen , Abou Aboubakar , Rosinah Montsho Maiyane , Mbah James Ajeck , Boyom Fabrice Fekam 
Published: December 2022

Abstract:
Native to the Southern Mediterranean region, Laurus nobilis L. (Family Lauraceae) is an
evergreen shrub or tree found in warm climate regions with high rainfall. The leaves and essential
oil of this plant have been widely used as condiments, spices, and flavoring agents in the culinary
and food industries. The whole plant is also used for the traditional treatment of various diseases,
including cough, asthma, hemorrhoids, rheumatic pain, diarrhea, intestinal, and cardiac diseases.
Previous phytochemical investigation of this plant demonstrated the presence of a variety of secondary
metabolites, especially terpenoids. The present study aims to critically analyze comprehensive
literature on the pharmacological activity and mechanisms of action of terpenoids from Laurus nobilis
L. The available information on the pharmacological activity of terpenoids from L. nobilis L. was
obtained from textbooks, theses, as well as published articles through a variety of libraries and electronic
databases. The present study demonstrated that L. nobilis is rich in terpenoids, with more than
200 entities identified in reported studies. Terpenoids from L. nobilis have shown a wide range of
pharmacological activities, including anti-inflammatory, antidiabetic, antifungal, antibacterial, immunomodulatory,
anticonvulsant, antioxidant and cytotoxic activities. The mechanisms of action of
most of these terpenoids included the imbalance of the ionic permeability of the cell membrane (anti-
inflammatory and antimicrobial activities), modulation of the effects of gamma-aminobutyric acid
(GABA) nergic neurotransmission (anticonvulsant activity), and the inhibition of inflammatory
responses, prevention of metastasis, and induction of apoptosis (cytotoxic effect), among others.
Referring to in vitro studies, terpenoids of L. nobilis L. have shown a variety of biological activities.
However, more cytotoxic and in vivo studies and detailed mechanisms of action of the bioactive
terpenoids are recommended.
Association of sodium-glucose cotransporter-2 inhibitors with time to dementia: a population-based cohort study
Authors: Wu Che-Yuan , Iskander Carina , Wang Christa , Xiong Lisa Y. , Shah Baiju R. , Edwards Jodi D. , Kapral Moira K. , Herrmann Nathan , Lanctôt Krista L. , Masellis Mario , Swartz Richard H. , Cogo-Moreira Hugo , MacIntosh Bradley J. , Rabin Jennifer S. , Black Sandra E. , Saskin Refik , Swardfager Walter 
Published: December 2022

<p> </p>
<p><strong>Objective</strong></p>
<p>Type 2 diabetes increases dementia risk, but clear evidence to recommend interventions that can mitigate that risk remains lacking. This population-based retrospective cohort study aimed to determine whether new use of sodium-glucose cotransporter-2 (SGLT2) inhibitors compared to dipeptidyl peptidase-4 (DPP4) inhibitors was associated with lower dementia risk.</p>
<p><strong>Research Design and Methods </strong></p>
<p>Ontario residents aged ≥66 years who were new users of an SGLT2 inhibitor or a DPP4 inhibitor from July 1st, 2016 to March 31st, 2021 entered the cohort. Incident dementia was identified using a validated algorithm for Alzheimer’s disease and related dementias. Propensity-score weighted Cox proportional hazards models were used to obtain adjusted hazard ratios (aHR) and confidence intervals (CI) for time to incident dementia. To address reverse causality and disease latency, the observation window started at 1-year lag-time from cohort entry. The primary analysis followed intention-to-treat exposure definition, and a secondary as-treated analysis was performed.</p>
<p><strong>Results </strong></p>
<p>Among 106,903 individuals, SGLT2 inhibitors compared with DPP4 inhibitors were associated with lower risk of dementia (14.2/1000 person-years; aHR [95% CI]=0.80 [0.71-0.89]) over a mean follow-up of 2.80 years from cohort entry. When stratified by different SGLT2 inhibitors, dapagliflozin exhibited the lowest risk (aHR [95% CI]=0.67 [0.53-0.84]), followed by empagliflozin (aHR [95% CI]=0.78 [0.69-0.89]), whereas canagliflozin showed no association (aHR [95% CI]=0.96 [0.80-1.16]). The as-treated analysis observed a larger association (aHR [95% CI]=0.66 [0.57-0.76]) than the intention-to-treat analysis.</p>
<p><strong>Conclusions</strong> </p>
<p>SGLT2 inhibitors showed an association with lower dementia risk in older people with type 2 diabetes. Randomized controlled trials are warranted. </p>
Sustained utilisation of skill set: assessing ex-agripreneurial trainees of agricultural school programme in Osun State, Nigeria
Authors: Oyebode Lukman Abiodun , Adeloye Kolawole Adelekan , Longe Peace Obehi 
Published: December 2022

Abstract
Charitable organisations complement government efforts in training young Nigerians in sustainable agricultural practices. A potent means of assessing the effectiveness of this training outlet/effort is the assessment of the sustained utilisation of the skill set acquired by its ex-agripreneurial trainees. A multistage sampling procedure was used to capture sample subjects. The last five sets of ex-trainees were purposively and proportionately sampled, this gave a sample size of 97. Both quantitative and qualitative data were elicited from the sample subjects. The majority (74.2 %) of the ex-trainees were male, middle-aged (38 years), made a net average monthly income of ₦ 46,618, and had an appreciable length of experience (11 years) as agripreneurs. The results of this study were as follows: training on the skill set received by the ex-agripreneural trainees was effective (75.3 %). Inadequate finance (x̅= 3.0), economic instability (x̅= 2.40) and poor state of infrastructure (x̅ = 2.23) were prominent among constraints associated with sustained utilisation of the skill set acquired. Enthusiasm about my enterprise (x̅= 1.72) was the attribute of an agripreneur possessed most. Sustained utilisation of skill set was high (61.9 %). A significant relationship was established between household size (r = 0,456), net average monthly income (r = 0.537), years of experience as an agripreneur (r = 0.509), perceived effectiveness of training received (r = 0.380), attributes of an entrepreneur possessed (r = 0.380), and sustained utilisation of skill set acquired. The study recommends that the training modules/templates are sustained and adapted by other training outlets/efforts owing to their effectiveness and the sustainability potentials it confers.
Semen characteristics and fertility response of crosses between white and black plumage indigenous turkeys under artificial insemination
Authors: Olubisi Ewuola Emmanuel , Isiaq Olarinre , Okiki Adagba , Tope Abioye , Oluwaseun Adeyemi , Samson Fabule 
Published: December 2022

Abstract
Semen quality and fertility in crossbreeding between white plumage and black plumage indigenous turkey hens using artificial insemination were investigated. Eighty-two healthy indigenous turkeys, comprising 72 hens (Thirty-two black and forty white) and 10 toms (five black and five white) were used. The turkeys were grouped into four treatments based on the breeding plans: T1 (White toms X White hens), T2 (Black toms X Black hens), T3 (White toms X black hens) and T4 (Black toms X White hens). Semen was harvested from white toms, pooled, and inseminated at 0.02ml into hens in T1 and T3. Semen harvested from black toms were also pooled and inseminated at same dose into hens in T2 and T4. White tom semen quality parameters were 97%, 91%, 96%, and 532×106 cells/mL for mass activity, motility, livability, and sperm concentration, respectively. Black tom semen quality parameters were 91%, 93%, 95%, and 293×106 cells/mL for mass activity, motility, livability, and sperm concentration, respectively. Egg fertility were 99.63% in T1, 99.81% (T2), 99.84%(T3), and 99.27% (T4). Hatchability in T1, T2, T3, and T4 were 57.67%, 72.54%, 67.65%, and 64.82%, respectively. Besides sperm concentration, semen quality parameters and fertility in indigenous turkey were not affected by plumage colour
The effects of minor oilseeds cakes on rumen metabolism and productive performances of ruminants
Authors: Oancea Alexandra-Gabriela , Dragomir Cătălin , Cișmileanu Ana 
Published: December 2022

Abstract
The article focuses on the chemical composition, nutritional value and the effects of four minor oilseeds’ cakes when used in ruminants’ nutrition. Although less abundant than the well-known major oilseeds, mechanical extraction of oils from the minor oilseeds retrieves important quantities of cakes which, beside a high content of crude protein have variable, yet important proportions of residual fat, upon the efficiency of the extraction processes and retains some nutritional properties of the seeds, including the content in bioactive substances.
The browse of the literature on minor oilseeds cakes retrieved scattered and contradictory data, implying a need for systematic comparison, among them and against a reference feed. Although specific literature is scarce, a number of articles reported the chemical composition of the four cakes, allowing their hierarchization and their comparison with the rapeseed cake, considered as reference feed.
On the other hand, the review identified numerous knowledge gaps, concerning the effects of the four cakes on rumen metabolism and their effects on animals’ productive performances. However, the literature review confirmed that the four cakes can be good substitutes of rapeseed cakes or similar feeds in ruminants’ nutrition, as long as the potential effects of bioactive substances taken into consideration.
Microsoft excel expert certification MO-201: results, analysis and key tips to succeed
Authors: Ali Shahid I. , Fitzpatrick Brian D. 
Published: December 2022

Abstract
Microsoft Excel skills are imperative in today’s competitive market and the skill is highly demanded by businesses. The MOS Excel Expert Certification (MO-201) validates the competency that one should build to meet employers’ expectations. The paper addresses the statistical mean rank difference in four skill groups of the certification test. Results of the four groups of the test were compared, using the Kruskal-Wallis’s test. The null hypothesis of the equality of the means for different groups was rejected at the 5% level of significance. Because the null hypothesis was rejected, the Conover post hoc test was applied for multiple pairwise comparisons, to discern which of the sample pair combinations were significantly different. The paper examines some of the concepts of groups 2 and 3 questions where students struggled the most and rendered insights to overcome those hurdles.
Rethinking Group Dynamics in Public Organizations: Starting Point for Behavioral Public Strategy Research
Authors: Horák Martin , Danko Lukáš , Kučera Filip 
Published: December 2022

Abstract

Purpose: The paper aims to explore group dynamics in the management and administration of the selected public organization. Specific interest is given to two fundamental domains of group dynamics: 1) communication processes and interaction patterns; 2) group cohesion and climate.

Methods: The approach is based on in-depth interviews with public employees representing various departments of a public organization. A total of 34 subjects participated in this study and provided primary data for coding and finding patterns. Both investigator and data triangulation are used to conceptualize group dynamics in the public organization.

Results: Public organizations’ employees face hardships in knowledge sharing and tend to misunderstand the agenda between various departments and citizens. The participation of citizens in decision making could be seen as a ‘double edged sword’ that contributes to the implementation of public projects, but often derails efficient organizational processes. Public organizations struggle with employee turnover, insufficient treatment of employee wellbeing, and unwillingness to pursue personal development.

Conclusion: Understanding and further defining the level of group dynamics among public employees is the first step towards adopting innovation approaches. The paper highlights the implications for public organizations with an overview of the behaviors needed for a smooth strategy process in development planning based on organizational forces that leads to a better understanding of group dynamics.
Cancer immunotherapy with CAR T cells: well-trodden paths and journey along lesser-known routes
Authors: Smole Anze 
Published: December 2022

Abstract

Background
Chimeric antigen receptor (CAR) T cell therapy is a clinically approved cancer immunotherapy approach using genetically engineered T cells. The success of CAR T cells has been met with challenges regarding efficacy and safety. Although a broad spectrum of CAR T cell variants and applications is emerging, this review focuses on CAR T cells for the treatment of cancer. In the first part, the general principles of adoptive cell transfer, the architecture of the CAR molecule, and the effects of design on function are presented. The second part describes five conceptual challenges that hinder the success of CAR T cells; immunosuppressive tumour microenvironment, T cell intrinsic properties, tumour targeting, manufacturing cellular product, and immune-related adverse events. Throughout the review, selected current approaches to address these issues are presented.

Conclusions
Cancer immunotherapy with CAR T cells represents a paradigm shift in the treatment of certain blood cancers that do not respond to other available treatment options. Well-trodden paths taken by pioneers led to the first clinical approval, and now the journey continues down lesser-known paths to treat a variety of cancers and other serious diseases with CAR T cells.
Representations of Real Numbers Induced by Probability Distributions on ℕ
Authors: Neunhäuserer Jörg 
Published: December 2022

Abstract
We observe that a probability distribution supported by ℕ, induces a representation of real numbers in [0, 1) with digits in ℕ. We first study the Hausdorff dimension of sets with prescribed digits with respect to these representations. Then, we determine the prevalent frequency of digits and the Hausdorff dimension of sets with prescribed frequencies of digits. As examples, we consider the geometric distribution, the Poisson distribution and the zeta distribution.