bluuebunny/crossref_metadata_2025_split huggingface dataset:
HDAC Inhibitor and BCL2 Selective Inhibitor Synergistically Exert Cytotoxicity on Human Myeloma Cells by Upregulating BIM Expression
Authors: Cao Liqin , Chen Haoguang , Chen Qingxiao , Gu Huiyao , Li Yi , Cao Wen , Liu Yang , Qu Jianwei , Hou Yifan , Chen Jing , Zhang Enfan , He Jingsong , Cai Zhen 
Published: March 2022

Abstract
Background
Multiple myeloma (MM) is the second most common hematologic malignancy with almost all patients eventually having relapse or refractory MM (RRMM), thus novel drugs or combination therapies are needed for improved prognosis. Chidamide and venetoclax, which target histone deacetylase and BCL2, respectively, are two promising agents for the treatment of RRMM.
Results
Herein, we found that chidamide and venetoclax synergistically exert an anti-myeloma effect in vitro in human myeloma cell lines (HMCLs) with a combination index (CI) < 1. Moreover, the synergistic anti-myeloma effect of these two drugs was demonstrated in primary MM cells and MM xenograft mice. Mechanistically, co-exposure to chidamide and venetoclax led to cell cycle arrest at G0/G1 and a sharp increase in DNA double-strand breaks (DSB). In addition, the combination of chidamide and venetoclax resulted in BCL-XL downregulation and BIM upregulation, and the latter protein was proved to play a critical role in sensitizing HMCLs to co-treatment.
Conclusion
In conclusion, these results proved the high therapeutic potential of venetoclax and chidamide combination in curing MM, representing a potent and alternative salvage therapy for the treatment of RRMM.
Portuguese Physical Literacy Assessment Questionnaire (PPLA-Q) for adolescents (15-18 years) from grades 10-12: item response theory analysis of the content knowledge questionnaire
Authors: Mota João , Martins João , Onofre Marcos 
Published: March 2022

Abstract

Background
Aims of this study were to assess construct validity (dimensionality and measurement invariance) and reliability of the previously developed Cognitive module of the Portuguese Physical Literacy Assessment – Questionnaire (PPLA-Q). Secondary aims were to assess whether using distractor information was useful for higher precision, and whether a total sum-score has enough precision for applied PE settings.
Methods
Parametric Item Response Theory (IRT) models were estimated using a final sample of 508 Portuguese adolescents (Mage= 16, SD = 1 years) studying in public schools in Lisbon. A retest subsample of 73 students, collected 15 days after baseline, was used to calculate Intraclass Correlation Coefficient (ICC) and Svenson’s ordinal paired agreement.
Results
A mixed 2-parameter nested logit + graded response model provided the best fit to the data, C2 (21) = 23.92, p = .21; CFI = .98; RMSEAC2= .017 [0,.043] with no misfitting items. Modelling distractor information provided an increase in available information and thus, reliability. There was evidence of differential item functioning in one item in favor of male students, however it did not translate in statistically significant differences at test level (sDTF = -0.06; sDTF% = -0.14). Average score reliability was low (marginal reliability = .60); while adequate reliability was attained in the − 2 to -1 θ range. ICC results suggest poor to moderate test-retest reliability (ICC = .56, [.38, .70]); while Svenson’s method resulted in 6 out of 10 items with acceptable agreement (> .70), and 4 remaining items revealing a small individual variability across time points. We found a high correlation (r = .91 [.90,.93]) among sum-score and scores derived from calibrated mixed model.
Conclusions
Evidence supports the construct validity of the cognitive module of the PPLA-Q to assess Content Knowledge in the Portuguese PE context for grade 10–12 (15–18 years) adolescents. This test attainted acceptable reliability for distinguishing student with transitional knowledge (between Foundation and Mastery), with further revisions needed to target full spectrum of θ. Its sum-score might be used in applied settings to get a quick overview of student’s knowledge; for precision IRT score is recommended. Further scrutiny of test-retest reliability is warranted in future research, along with the use of 3-parameter logistic models.
Tile-Based Microscopic Image Processing For Malaria Screening Using Deep Learning Approach
Authors: Abdurahman Fetulhak , Fante Kinde Anlay 
Published: March 2022

Abstract
Background: Manual microscopic examination remains the golden standard for malaria diagnosis. However, it is cumbersome and requires the experience of pathologists for accurate diagnosis. The shear workload and challenges involved in manual microscopy drives for alternative computer-aided diagnosis techniques. While the importance of computer-aided diagnosis is increasing at an enormous pace fostered by the advancement of deep learning algorithms, there are still challenges. Existing state-of-the-art (SOTA) deep learning-based object detection models suffer from effectively detecting small objects which are less represented on benchmark datasets and are affected by the loss of detailed spatial information due to in-network feature map downscaling. The problem even becomes harder when the input image is high resolution. This is due to the fact that existing SOTA models will not directly process high-resolution images limited by their low-resolution network input size. ﻿Methods: In this study, an effective and robust tile-based image processing approach was proposed to enhance malaria parasite detection performance of SOTA object detection models. Three YOLOV4 based object detectors were adopted considering their detection speed and accuracy. The proposed detection models were developed by using tiles generated from 1,780 high-resolution P. falciparum-infected thick smear microscopic images. External validation was performed to verify the detection accuracy and generalization ability of the proposed models on three datasets acquired from a different domain.Results: The best-performing model leveraging the proposed tile-based approach significantly outperforms its baseline method (Recall, [95.3%] vs [57%] and Average Precision, [87.1%] vs [76%]). In addition, the proposed method achieved state-of-the-art performance compared with previous research works which use different machine learning techniques on similar datasets.Conclusions: The obtained qualitative and empirical results show that the proposed method reveals a fundamental performance improvement for the detection of P. falciparum from thick smear microscopic images while maintaining real-time speed. Furthermore, the proposed method could have the potential to assist and reduce the workload of laboratory technicians in malaria-endemic remote areas in developing countries where there is a critical skill gap and shortage of experts.
Gender-Related Differences in the association of serum levels of vitamin D with body mass index in northern Iranian population: The PERSIAN Guilan Cohort Study (PGCS)
Authors: Joukar Farahnaz , Asgharnezhad Mehrnaz , Naghipour Mohammadreza , Mojtahedi Kourosh , Salari Arsalan , Mansour-Ghanaei Alireza , Mansour-Ghanaei Fariborz 
Published: March 2022

Abstract
Background
Vitamin D insufficiency has now become a global problem throughout the world. The association between increasing body mass index (BMI) and vitamin D insufficiency has attracted great attention in recent researches. The aim was to study if BMI was independently associated with serum 25-hydroxyvitamin D in a large population-based study, specify by gender.
Methods
Data on 9520 adults 35 years and older participating in PERSIAN Guilan Cohort Study (PGCS) were used. Serum levels of 25-hydroxy vitamin D less than 20 ng/mL (50 nmol/L) was used as a measure of vitamin D inadequacy. Multiple logistic and linear regression analyses were used to estimate the strength of the association between vitamin D and BMI before and after adjusting for demographic factors and lifestyle variables.
Results
After adjustment in male population, overweight (adjusted OR= 1.2, P = 0.03) and obese (adjusted OR= 1.4, P = 0.001) individuals were more likely to have vitamin D inadequacy than normal weight counterparts. Moreover, there was a weak inverse linear association between BMI and serum 25 OHD levels in males (β = -0.14, P value= 0.001). In contrast, no significant associations between BMI and serum 25 OHD levels were observed in females. In male population, higher BMI were associated with lower serum vitamin 25 (OH) D levels.
Conclusion
However, this association was not observed in female population. The suggestion of current study for public health was special consideration to serum vitamin D levels in over weight and obese males.
Violência obstétrica e humanização no parto. Percepção de alunos de graduação em Medicina e Enfermagem
Authors: Alves Costa Juliana , de Almeida Silveira Juliana , Da Cunha Gonçalves Sebastião Jorge , Almeida de Souza Maria Cristina 
Published: March 2022

A violência obstétrica encontra-se em diversas expressões e omissões direcionadas a mulher durante o pré-natal, parto e/ou puerpério, causando dor e sofrimento desnecessários, desrespeitando sua autonomia e integridade física e mental. A humanização, por sua vez, vem destacando-se na assistência ao parto ao defender o protagonismo feminino da mulher ao parir. Diante isso, a humanização deve ser amplamente inserida na formação acadêmica para que os futuros profissionais atuem de forma a acolher a paciente, respeitando suas vontades e desejos. Teve por objetivo verificar a percepção dos estudantes do internato do Curso de Medicina e do estágio supervisionado do Curso de Enfermagem da Universidade de Vassouras sobre a violência obstétrica e a humanização na assistência ao parto. Foi realizada uma pesquisa transversal, de natureza quantitativa, cujos dados foram coletados, via google forms, utilizando-se um questionário estruturado com 10 perguntas. A amostra, por conveniência, não probabilística, foi constituída por 102 estudantes, sendo 72 do curso de medicina e 30 do curso de enfermagem. Dentre as respostas, entre as com maior taxa de divergência estão a realização da manobra de Kristeller e o incentivo ao uso de fórmulas em detrimento ao aleitamento materno exclusivo sem a devida indicação. Já as com maior número de concordância estão: o incentivo o desmame precoce e induzir a cesariana sem indicação. Conclui-se que os estudantes, apesar de conhecerem os conceitos de VO, divergiram em suas percepções, sendo os do curso de enfermagem aqueles que alcançaram maior percentual de respostas corretas.
Palavras-chave: Parto Humanizado; Violência Obstétrica; Humanização da Assistência.
Fullerenes For Anticancer Drug Targeting: Teaching An Old Dog A New
Trick
Authors: Sharma Manu , Dhiman Shikha , Kaur Amardeep 
Published: March 2022

Abstract:
Fullerenes are the allotropic form of carbon consisting of a cage-like structure due to which
they have attained special attention from researchers since their discovery in 1985. The unique chemical
and physical properties of fullerene have attracted researchers to develop a variety of its biomedical
applications. The closed cage structure of fullerenes can be used for various drug delivery applications
and can also act as a medium for controlled release formulations. The development of targeted
anticancer drug and drug delivery systems is one of the most challenging fields, which is widely studied
and researched. In this review, we aim to provide a comprehensive review on the most recent advances
in fullerenes as targeted anticancer drug delivery systems along with their therapeutic applications
and challenges, thus serving the pharmaceutical and biotechnology community.
Synthesis and Evaluation of Polyethylene Glycol-4000-Co-Poly (AMPS)
Based Hydrogel Membranes for Controlled Release of Mupirocin for
Efficient Wound Healing
Authors: Minhas Muhammad Usman , Ahmad Sarfaraz , Khan Kifayat Ullah , Sohail Muhammad , Abdullah Orva , Khalid Ikrima , Malik Nadia Shamshad 
Published: March 2022

Background:
Chronic wound healing is a major challenge for the health care system around
the globe. The current study was conducted to develop and characterize chemically cross-linked polyethylene
glycol-co-poly (AMPS) hydrogel membranes to enhance the wound healing efficiency of antibiotic
mupirocin (MP).

Methods:
Free radical polymerization technique was used to develop hydrogel membranes. In an aqueous
medium, polymer PEG-4000 was cross-linked with the monomer 2-acrylamido-2-methylpropane
sulfonic acid (AMPS) in the presence of initiators ammonium peroxide sulfate (APS) and sodium hydrogen
sulfite (SHS). N, N-Methylene-bis-acrylamide (MBA) was used as a cross-linker in preparing
hydrogel membranes. Developed membranes were spherical, transparent, and had elasticity. FTIR,
TGA/DSC, and SEM were used to characterize the polymeric system. Swelling behavior, drug loading,
and release pattern at pH of 5.5 and 7.4, irritation study, ex vivo drug permeation, and deposition study
were also evaluated.

Results:
Formed membranes were spherical, transparent, and had elasticity. The formation of a stable
polymeric network was confirmed by structural and thermal analysis. Evaluation of the drug permeability
in the skin showed good permeation and retention capabilities. No irritancy to the skin was observed.

Conclusion:
Based on the results obtained, the present study concluded that the formulated stable network
might be an ideal network for the delivery of mupirocin in skin infections.
The Antibacterial Potential of Ciprofloxacin Hybrids against Staphylococcus
aureus
Authors: Zang Wenhua , Li Danxia , Gao Li , Gao Shuang , Hao Pengfei , Bian Hua 
Published: March 2022

Abstract:
Staphylococcus aureus (S. aureus), an important pathogen of both humans and animals, can cause a variety of infections at any site of the body. The evolution of S. aureus resistance is no-torious, and the widespread of drug-resistant S. aureus, especially methicillin-resistant S. aureus (MRSA), has made the treatment difficult in recent decades. Nowadays, S. aureus is among the leading causes of bacterial infections, creating an urgent need for the development of novel antibac-terial agents. Ciprofloxacin, characterized by high clinical efficacy, is a broad-spectrum antibacteri-al agent with frequency of prescription for various Gram-positive and Gram-negative pathogens, many of which are resistant to a wide range of antibiotics. However, the long-term and widespread use of this antibiotic has led to the emergence of ciprofloxacin-resistant pathogens, and ciprofloxa-cin-resistant S. aureus has been noted in clinical practice. Ciprofloxacin hybrids have been recog-nized as advanced chemical entities to simultaneously modulate multiple drug targets in bacteria, so ciprofloxacin hybrids have the potential to overcome drug resistance. The present review provides an overview of ciprofloxacin hybrids with anti-S. aureus potential that has been reported in the last decade with an emphasis on their structure-activity relationships and mechanisms of action.
Does Methylene Blue Satisfy an Option in COVID-19 ARDS
Authors: Yella Sri Hari Tanguturi , Yella Sree Sudha Tanguturi , Sasanka Kota Sesha Brahma Shree Krishna , Thangaraju Pugazhenthan 
Published: March 2022

Background:
In COVID-19, the respiratory tract is usually affected by SARS-CoV-2 infection.
Due to viral transmission in the blood and an overwhelming inflammatory response, including
cytokine storm, the condition can progress to acute respiratory distress syndrome and failure. Methylene
blue is the only medicine that has been shown to reduce the excessive generation of reactive
species and cytokines.

Case Presentation:
A 51-year-old male patient came to the hospital with shortness of breath. At room
air, the patient was having 70% Spo2. The patient was treated with a noninvasive ventilator (NIV) and
Standard of care (SOC). Due to prolonged hypoxia and respiratory distress, the patient was treated with
NIV and the methylene blue (MB) was given in a humidifier for 5 days.

Result:
Methylene blue resulted in a significant decrease in respiratory distress and a steep rise in Spo2.

Conclusion:
We suggest trying methylene blue as an additional intervention in COVID-related acute
respiratory distress to avoid the disease's devastating consequences.
Synthesis, In vitro Antibacterial and Antimycobacterial Activity and Docking
Study of Thieno(3,2-e)(1,2,4)triazolo(1,5-c)pyrimidines
Authors: Malothu Narender , Jojula Malathi , Kaki Venkat Rao , Adidala Raghuram Reddy , Akkinepally Raghuram Rao 
Published: March 2022

Background:
Emergence of drug resistance and severe side effects with current an-titubercular drugs urges the development of more efficacious and safer new agents. The present study focused on this direction to develop new hetero-fused pyrimidines as potential antitubercu-lar agents.

Objective:
The objective of the study was to synthesize and assess the antibacterial and antimy-cobacterial activity of novel 1,2,4-triazole ring bearing hetero-fused thienopyrimidines (6a-j & 7a-j). Also to evaluate the binding pattern of synthesized molecules at the target site and study their ADME properties by in silico tools.

Methods:
Two series of hetero fused thienopyrimidines (6a-j & 7a-j) were synthesized and tested for their antibacterial potentiality against B. subtilis, S. aureus, E. coli, and K. pneumonia. Com-pounds with potential antibacterial activity were further tested for their antitubercular activity against Mycobacterium tuberculosis (MTB) H37Rv and an isoniazid (INH)-resistant clinical sam-ple of MTB using broth microdilution method. The binding efficacy at the enzyme site was eval-uated by the molecular docking study using pantothenate synthetase (MTB-PS) (PDB: 3IVX) as the target protein. Further, in silico ADME properties of title compounds were explored by Swiss ADME online tools.

Results:
In this study, few compounds were found promising in exhibiting potent inhibitory ac-tivity against E. coli and MTB. Among these compounds, 6h (MTB: MIC-17.13±0.88 μM) and 6i (MTB: MIC-17.55±0.72 μM) displayed significant antimycobacterial activity. The molecular docking results suggested the efficient binding of biologically potential molecules.

Conclusion:
Compounds bearing N-benzyl moiety at the core nucleus with a p-nitro aryl side chain (6h) exhibited significant antitubercular activity. In silico studies showed effective binding at the target site and also indicated good compatibility in ADME properties.
Sodium-Glucose Cotransporter-2 Inhibitor and Glucagon-Like Peptide-1 Receptor Agonist Combination Therapy in Type 2 Diabetes: Protocol for a Kidney End Points Real-world Study (COMBi-KID Study)
Authors: Feher Michael , Hinton William , Forbes Anna , Munro Neil , Joy Mark , Wheeler David , de Lusignan Simon 
Published: March 2022

Background
Sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) are both considered to be part of standard care in the management of glycemia in type 2 diabetes. Recent trial evidence has indicated benefits on primary kidney end points for individual drugs within each medication class. Despite the potential benefits of combining SGLT2is and GLP-1RAs for glycemia management, according to national and international guideline recommendations, there is currently limited data on kidney end points for this drug combination.

Objective
The aims of the study are to assess the real-world effects of combination SGLT2i and GLP-1RA therapies for diabetes management on kidney end points, glycemic control, and weight in people with type 2 diabetes who are being treated with renin-angiotensin system blockade medication.

Methods
This retrospective cohort study will use the electronic health records of people with type 2 diabetes that are registered with general practices covering over 15 million people in England and Wales and are included in the Oxford-Royal College of General Practitioners Research and Surveillance Centre network. A propensity score–matched cohort of prevalent new users of SGLT2is and GLP-1RAs and those who have been prescribed SGLT2is and GLP-1RAs in combination will be identified. They will be matched based on drug histories, comorbidities, and demographics. A repeated-measures, multilevel, linear regression analysis will be performed to compare the mean change (from baseline) in estimated glomerular filtration rate at 12 and 24 months between those who switched to combined therapy and those continuing monotherapy with an SGLT2i or GLP-1RA. The secondary end points will be albuminuria, serum creatinine level, glycated hemoglobin level, and BMI. These will also be assessed for change at the 12- and 24-month follow-ups.

Results
The study is due to commence in March 2022 and is expected to be complete by September 2022.

Conclusions
Our study will be the first to assess the impact of combination SGLT2i and GLP-1RA therapy in type 2 diabetes on primary kidney end points from a real-world perspective.

International Registered Report Identifier (IRRID)
PRR1-10.2196/34206
Puntos de partida, metas y rutas de prospección en investigaciones etnomusicológicas y etnolingüísticas
Authors: Nava L. E. Fernando 
Published: March 2022

Son mencionados aquí algunos de los temas de interés, estudios, publicaciones y motivos de investigación del autor de este texto, correspondientes a los ámbitos de la Etnomusicología y la Etnolingüística. Los tópicos principalmente referidos son: la música y la literatura tradicionales de México, considerando tanto formas arraigadas entre la población hispanohablante, como otras que respectivamente se encuentran presentes entre algunos pueblos indígenas; ciertas expresiones musicales de los pueblos purépecha, seri y zapoteco, principalmente; algunas expresiones verbales estetizadas, en determinadas lenguas indígenas; así como aspectos de la relación lengua-cultura. Se hace referencia a los factores que estimularon los estudios, a algunas de las decisiones que median entre los resultados de la investigación y la selección-preparación de los datos preparados para las publicaciones, así como a varias preguntas abiertas o sin resolver. Algunos de los casos se presentan con reflexiones teórico-metodológicas que pretenden ser de utilidad en el estudio de los temas aquí mencionados.
Tenazitzimitl y otros relatos de la huasteca veracruzana
Authors: Granados Vázquez Berenice Araceli 
Published: March 2022

Entrevista a Darina Melisa Hernández Martínez, en Xochimilco, Ixhuatlán de Madero, Veracruz de Ignacio de la Llave
La entrevista que aquí se presenta tuvo lugar en octubre del 2014, en el pueblo de Xochimilco, municpio de Ixhuatlán de Madero, Veracruz de Ignacio de la Llave, una comunidad nahua ubicada en el corazón de la Huasteca veracruzana. Esta documentación forma parte del proyecto de investigación “Entidades femeninas acuáticas” (2009) de la Dra. Berenice Araceli Granados Vázquez.