bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of CPY3A5 Genetic Polymorphisms on the Pharmacokinetics of Extendedrelease and Immediate-release Tacrolimus Formulations in Renal Transplant Recipients: A Systematic Review and Meta-analysis
Authors: Xie Qiufen , Xiang Qian , Liu Zhiyan , Mu Guangyan , Zhou Shuang , Zhang Zhuo , Ma Lingyue , Cui Yimin 
Published: September 2021

Background :
Although the pharmacokinetic variability of Tacrolimus (Tac) metabolism is primarily influenced
by CYP3A5 genotypes, the potential effect according to CYP3A5 polymorphisms in Tac extended-release
(Tac-ER) and immediate-release (Tac-IR) and between these formulations’ conversion needs further investigation.
The purpose of this study was to clarify the association of CYP3A5 genotypes and pharmacokinetics of different Tac
formulations in renal transplant recipients.

Methods :
PubMed, EMBASE, and Cochrane Library databases were searched for eligible studies (protocol registration
No. CRD 42019133790 in PROSPERO network). The summary weighted mean difference with 95% confidence
intervals was calculated for pharmacokinetic parameters using the random-effects model according to posttransplantation
periods, genotypes and formulations. Sensitivity analysis, publication bias, and subgroup analyses
were conducted.

Results :
A total of 27 studies involving 2,713 renal transplant recipients were adopted. Whether patients treated with
Tac-ER or Tac-IR, CYP3A5 non-expressors (*3/*3) had a decreased daily dose and CL/F, an increased Ctrough,
Ctrough/D, AUC0-24h/D and Cmax/D than expressors (*1/*1 or *1/*3) at most post-transplantation periods. Furthermore,
when 1:1 dose conversion from Tac-IR to Tac-ER (all at ≥12 months post-transplantation), Ctrough and Cmax were
decreased in both CYP3A5 non-expressors and expressors, while daily dose was only decreased in CYP3A5 nonexpressors
and AUC0-24h was only decreased in CYP3A5 expressors. Finally, subgroup analyses indicated that ethnicity,
mean age, and male percentage influenced daily dose and Ctrough of Tac, especially for Tac-IR.

Conclusion:
The results indicated that CYP3A5 genotypes affect the pharmacokinetics of Tac in renal transplant
recipients in both formulations and between formulations’ conversion. Future studies should be exploring more other
associations of CYP3A5 genotypes and the pharmacodynamics of Tac.
Some Scaffolds as Anti-leishmanial Agents: A Review
Authors: Mahender Thatikayala , Pankaj Wadhwa , Kumar Singh Pankaj , Ankur Vaidya , Kumar Sahu Sanjeev 
Published: September 2021

Abstract:
Leishmaniasis is a parasitic infectious neglected tropical disease transmitted to humans by
the parasites of Leishmania species. Mainly, three types of leishmaniases are usually observed: visceral
(VL), cutaneous (CL), and mucocutaneous leishmaniasis. In many western countries, almost
700,000 to 1 million people suffer from leishmaniasis, and it is estimated that around 26000 to 65000
deaths occur from leishmaniasis. Few drugs are available for its treatment; however, none of them are
ideal for leishmaniasis due to long treatment, discomfort mode of administration, risk of high-level
toxicity, high resistance, etc. Hence, so many patients are unable to take complete treatment due to the
high drug resistance. The present review will focus on antileishmanial activity of reported derivatives
of betacarboline, chalcone, azole, quinoline, quinazoline, benzimidazole, benzadiazapine, thiaazoles,
semicarbazone, and hydontoin analogues. We believe that this present study will be helpful for researchers
to design new antileishmanial agents.
Current Challenges in Targeting Tumor Desmoplasia to Improve the Efficacy of Immunotherapy
Authors: Kasperska Anna , Borowczak Jędrzej , Szczerbowski Krzysztof , Stec Ewa , Ahmadi Navid , Szylber Łukasz 
Published: September 2021

:
Desmoplasia is crucial for the development, progression and treatment of immune-resistant
malignancies. Targeting desmoplasia-related metabolic pathways appears to be an interesting
approach to expand our stock of disposable anti-tumor agents. CXCL12/CXCR4 axis inhibition reduces
fibrosis, alleviates immunosuppression and significantly enhances the efficacy of PD-1 immunotherapy.
CD40L substitute therapy may increase the activity of T-cells, downregulate
CD40+, prolong patients’ survival and prevent cancer progression. Although FAPα antagonists
used in preclinical models did not lead to permanent cure, an alleviation of immune-resistance,
modification of desmoplasia and a decrease in angiogenesis were observed. Targeting DDR2 may
enhance the effect of anti-PD-1 treatment in multiple neoplasm cell lines and has the ability to overcome
the adaptation to BRAF-targeted therapy in melanoma. Reprogramming desmoplasia could
potentially cooperate not only with present treatment, but also other potential therapeutic targets.
We present the most promising metabolic pathways related to desmoplasia and discuss the emerging
strategies to improve the efficacy of immunotherapy.
Neuroinflammatory Signaling in the Pathogenesis of Alzheimer’s Disease
Authors: Uddin Md. Sahab , Kabir Md. Tanvir , Jalouli Maroua , Rahman Md. Ataur , Jeandet Philippe , Behl Tapan , Alexiou Athanasios , Albadrani Ghadeer M. , Abdel-Daim Mohamed M. , Perveen Asma , Ashraf Ghulam Md 
Published: September 2021

:Alzheimer’s disease (AD) is a chronic neurodegenerative disease characterized by the formation of intracellular neurofibrillary tangles (NFTs) and extracellular amyloid plaques. Growing evidence has suggested that AD pathogenesis is not only limited to the neuronal compartment but also strongly interacts with immunological processes in the brain. On the other hand, aggregated and misfolded proteins can bind with pattern recognition receptors located on astroglia and microglia and can in turn induce an innate immune response, characterized by the release of inflammatory mediators, ultimately playing a role in both the severity and the progression of the disease. It has been reported by genome-wide analysis that several genes which elevate the risk for sporadic AD encode for factors controlling the inflammatory response and glial clearance of misfolded proteins. Obesity and systemic inflammation are examples of external factors which may interfere with the immunological mechanisms of the brain and can induce disease progression. In this review, we discussed the mechanisms and essential role of inflammatory signaling pathways in AD pathogenesis. Indeed, interfering with immune processes and modulation of risk factors may lead to future therapeutic or preventive AD approaches.
The Comprehensive Neural Mechanism of Oxytocin in Analgesia
Authors: Yang Liu-Nan , Chen Kai , Yin Xiao-Ping , Liu Dan , Zhu Ling-Qiang 
Published: September 2021

:
Oxytocin (OXT) is a nine amino acid neuropeptide hormone that has become one of the
most intensively studied molecules in the past few decades. The vast majority of OXT is
synthesized in the periventricular nucleus and supraoptic nucleus of the hypothalamus, and a
few are synthesized in some peripheral organs (such as the uterus, ovaries, adrenal glands,
thymus, pancreas, etc.) OXT modulates a series of physiological processes, including
lactation, parturition, as well as some social behaviors. In addition, more and more attention
has recently been focused on the analgesic effects of oxytocin. It has been reported that OXT
can relieve tension and pain without other adverse effects. However, the critical role and
detailed mechanism of OXT in analgesia remain unclear. Here, this review aims to summarize
the mechanism of OXT in analgesia and some ideas about the mechanism.
7,8-Dihydroxyflavone and Neuropsychiatric Disorders: A Translational
Perspective from the Mechanism to Drug Development
Authors: Zhu Guoqi , Yang Shaojie 
Published: September 2021

:
7,8-Dihydroxyflavone (7,8-DHF) is a kind of natural flavonoids, with the potential to cross the blood-brain barrier. 7,8-DHF effectively mimics the effect of brain-derived neurotrophic factor (BDNF) in the brain to selectively activate tyrosine kinase receptor B (TrkB) and downstream signaling pathways, thus playing a neuroprotective role. The preclinical effects of 7,8-DHF have been widely investigated in the neuropsychiatric disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), depression and memory impairment. Besides the effect on TrkB, 7,8-DHF could also function through fighting against oxidative stress, cooperating with estrogen receptors or regulating intestinal flora. This review focuses on the recent experimental studies on depression, neurodegenerative diseases and learning and memory function. Additionally, the structural modification and preparation of 7,8-DHF were also concluded and proposed, hoping to provide reference for the follow-up research and clinical drug development of 7,8-DHF in the field of neuropsychiatric disorders.
Identification of Disease-specific Single Amino Acid Polymorphisms Using a Simple Random Forest at Protein-level
Authors: He Jian , Yuan Rongao , Xu Lei , Guo Yanzhi , Li Menglong 
Published: September 2021

Background:
The number of human genetic variants deposited into publicly available databases
has been increasing exponentially. Among these variants, non-synonymous single nucleotide
polymorphisms (nsSNPs), also known as single Amino Acid Polymorphisms (SAPs), have been
demonstrated to be strongly correlated with phenotypic variations of traits/diseases.

Objective:
However, the detailed mechanisms governing the disease association of SAPs remain unclear.
Thus, further investigation of new attributes and improvement of the prediction becomes more
and more urgent since amount of unknown disease-related SAPs need to be investigated.

Methods:
Based on the principle of Random Forest (RF), we firstly constructed a new effective prediction
model for SAPs associated with a particular disease from protein sequences. Four usual sequence
signature extractions were separately performed to select the optimal features. Then SAP peptide
lengths from 12 to 202 were also optimized.

Results:
The optimal models achieve higher than 90% accuracy and Area Under the Curve (AUC) of
over 0.9 on all 11 external testing datasets. Finally, the good performance on an independent test set
with an accuracy higher than 95% proves the superiority of our method.

Conclusion:
In this paper, based on Random Forest (RF), we constructed 11 disease-association prediction
models for SAPs from the protein sequence level. All models yield prediction accuracy higher
than 90% and Area Under the Curve (AUC) more than 0.9. Our method only using the information of
protein sequences are more universal than those that depend on some additional information or predictions
about the proteins.
The Effect of Dialectical Behavioral Therapy on Emotion Dysregulation in Couples
Authors: Rady Ahmed , Molokhia Tarek , Elkholy Nehal , Abdelkarim Ahmed 
Published: September 2021

Background:
Divorce rates have increased during the last decade, leading to a greater focus of marital scholars on the importance of understanding couple-maintaining strategies within marital life. Distresses in couples are attributable to difficulties controlling felt, experienced, and expressed emotions; thus, emotion dysregulation is a core stressor in couples with maladaptive responses.

Objective:
The aim of the study was to evaluate the effect of Dialectical Behaviour Therapy (DBT) on outpatient couples to treat emotion dysregulation.

Methods:
We recruited 20 couples with marital distress in which partners presented emotion dysregulation. We offered the couples the opportunity to join a couple DBT group at their convenience and based on the immediate availability of treatment slots. We measured the treatment efficacy using psychometric tools (the Difficulties in Emotion Regulation Scale (DERS) and the Dyadic Adjustment Ccale (DAS) at baseline and after DBT therapy.

Results:
Both male and female partners presented significant improvements in marital adjustment DAS and emotion regulation scores. Female partners showed significantly greater amplitude changes in both scales. Female partners showed significant improvement in most DERS subscales (except the GOALS subscale); on the other hand, male partners showed significant improvements in impulse, awareness, strategies, and clarity subscales. We found significant improvements in most DAS subscales in both sexes; only affectional expression remained unchanged before and after therapy.

Conclusion:
DBT for couples is an effective approach to treat emotion dysregulation.
Complete Healing and Short-term Treatment by Argania Honey Dressing
in a Venous Leg Ulcer: A Case Report
Authors: Khattabi Leila , Raghay Kawtar , Dakkach Mohamed , Allouch Mohamed 
Published: September 2021

Background:
Recent advances in care show that inadequate management of the healing
process in wounds and the development of bacterial infections lead to increased morbidity. Health
professionals have progressively recognized the value of choosing suitable dressings to manage
wounds, particularly in developing countries. Honey has been used for thousands of years as a
wound dressing and is considered a biologic treatment due to its multiple bioactivities related to
the healing process.

Objective:
The aim of this case report is to demonstrate that Argania Honey dressing improves the
healing process in a venous leg ulcer.

Method:
Pure raw Argania honey (Argania spinosa, endemic tree in Southwestern Morocco) with
no additives, pasteurization or manipulation was used, which was provided by local beekeepers. A
mechanical debridement process was achieved previously to the application of honey dressings to a
venous leg ulcer of a 67-year-old woman affected by type II diabetes for 11 years.

Results:
The Argania honey dressing accompanied by mechanical debridement process demonstrated
a rapid recovery and complete healing of the wound for 12 weeks approximately (79 days).

Conclusion:
This Moroccan honey (Argania) experienced for the first time in venous leg ulcer management
may represent a good alternative to treat other types of wounds. Further investigations
by using Argania honey dressing are required to explain its effect and the mechanisms involved in
the improvement of the healing process.
A Brief Overview on the Contribution of Machine Learning in Systems Neuroscience
Authors: Orrù Graziella , Conversano Ciro , Ciacchini Rebecca , Gemignani Angelo 
Published: September 2021

Background:
The use of Machine Learning (ML) is witnessing exponential
growth in the field of artificial intelligence (AI) and neuroscience, in particular in subdisciplines
such as Systems Neuroscience (SN), as a viable alternative to the use of classical statistical
techniques. The combination of this interconnection allows a more detailed study of
algorithms and neural circuits that emulate core cognitive processes. ML toolbox includes
algorithms that are suited to solving problems of classification, regression, clustering, and
anomaly detection.

Objective:
The aim of the present opinion was to exemplify the contribution of ML in the
field of SN in three different fields: 1) cognitive modelling; 2) neuroimaging; 3) analysis of
clinical datasets.

Method:
We gathered evidence from the relevant literature related to the interaction between
neuroscience and AI and the impact of ML in SN.

Results :
ML is specifically suited to the analysis of large clinical neuroscience datasets. Experimental
results in neuroscience are hard to replicate for a number of reasons, and ML may
contribute to attenuating these replicability issues via the ubiquitous use of cross-validation
procedures. While ML modelling is primarily focused on prediction accuracy, one of the
drawbacks in ML is the opacity of various algorithms that resist intuitive understanding.

Conclusions:
Future avenues of research have already been traced and include increased interpretability
of currently opaque ML models functioning and causal analysis. Causal analysis
is intended to distinguish between spurious associations and cause-effect relationships and
is a primary interest in both clinical medicine and basic neuroscience.
N-Acetyl Cysteine in Rodenticide Poisoning: A Systematic Review and
Meta-Analysis
Authors: Thunga Girish , Rashid Muhammed , Chandran Viji Pulikkel , Nair Sreedharan , Muthu Deepa Sudalai , Pappuraj Jemima , Jacob Krupa Ann , Sridhar Balaji , Mark Karen , Hyder Shabnam , Khan Sohil 
Published: September 2021

Background:
Treatment with N-Acetyl Cysteine (NAC) in rodenticide poisoning has not
been well established due to mixed study results and insufficient evidence. This review aimed to
summarize the clinical benefits of NAC in the management of rodenticide poisoning.

Method:
This review follows the PICOS framework and the PRISMA guidelines. Pub-
Med/MEDLINE, Scopus, and the Cochrane library were searched to identify the published literature
from inception to September 2020, and a reference search was performed for additional relevant studies.
The English language studies addressing the use of NAC in rodenticide poisoning were considered
for the review. We considered all experimental and observational studies due to the insufficient number
of interventional studies.

Results:
Ten studies (two RCTs, four observational, and four descriptive) out of 2,178 studies with
492 participants were considered for the review. Only six studies (two RCTs, one prospective, and
three retrospective studies) reported recovery and mortality. Pooled results of RCTs (n=2) showed a
significant recovery rate (Odds Ratio [OR]: 3.97; 95% Confidence Interval [CI]:1.69-9.30), whereas
summary estimates of prospective and retrospective studies recorded a non-significant effect. Metaanalysis
of RCTs (OR: 0.25; 95% CI: 0.11-0.59; n=2) and retrospective studies (OR: 0.34; 95% CI:
0.15-0.78; n=3) showed a significant reduction in mortality, whereas pooled analysis of prospective
studies recorded a non-significant effect. A significant reduction in intubation or ventilation (OR:
0.25; 95% CI: 0.11-0.60; 2 RCTs) and a non-significant (P=0.41) difference in duration of hospitalization
was observed with NAC when compared to the non-NAC treated group. The quality of the included
studies appeared to be moderate to high.

Conclusion:
Our findings indicate that NAC showed better survival and lower mortality rate when
compared to non-NAC treated group; hence NAC can be considered for the management of rodenticide
poisoning.

PROSPERO registration number:
CRD42020154376.
Public Perceptions of Diabetes, Healthy Living, and Conversational Agents in Singapore: Needs Assessment
Authors: Dhinagaran Dhakshenya Ardhithy , Sathish Thirunavukkarasu , Kowatsch Tobias , Griva Konstadina , Best James Donovan , Tudor Car Lorainne 
Published: September 2021

BackgroundThe incidence of chronic diseases such as type 2 diabetes is increasing in countries worldwide, including Singapore. Health professional–delivered healthy lifestyle interventions have been shown to prevent type 2 diabetes. However, ongoing personalized guidance from health professionals is not feasible or affordable at the population level. Novel digital interventions delivered using mobile technology, such as conversational agents, are a potential alternative for the delivery of healthy lifestyle change behavioral interventions to the public.ObjectiveWe explored perceptions and experiences of Singaporeans on healthy living, diabetes, and mobile health (mHealth) interventions (apps and conversational agents). This study was conducted to help inform the design and development of a conversational agent focusing on healthy lifestyle changes.MethodsThis qualitative study was conducted in August and September 2019. A total of 20 participants were recruited from relevant healthy living Facebook pages and groups. Semistructured interviews were conducted in person or over the telephone using an interview guide. Interviews were transcribed and analyzed in parallel by 2 researchers using Burnard’s method, a structured approach for thematic content analysis.ResultsThe collected data were organized into 4 main themes: use of conversational agents, ubiquity of smartphone apps, understanding of diabetes, and barriers and facilitators to a healthy living in Singapore. Most participants used health-related mobile apps as well as conversational agents unrelated to health care. They provided diverse suggestions for future conversational agent-delivered interventions. Participants also highlighted several knowledge gaps in relation to diabetes and healthy living. Regarding barriers to healthy living, participants mentioned frequent dining out, high stress levels, lack of work-life balance, and lack of free time to engage in physical activity. In contrast, discipline, preplanning, and sticking to a routine were important for enabling a healthy lifestyle.ConclusionsParticipants in this study commonly used mHealth interventions and provided important insights into their knowledge gaps and needs in relation to changes in healthy lifestyle behaviors. Future digital interventions such as conversational agents focusing on healthy lifestyle and diabetes prevention should aim to address the barriers highlighted in our study and motivate individuals to adopt healthy lifestyle behavior.
El ocaso de los dioses de la prosperidad después del TLC y en pleno bicentenario. Neoliberalismo, desigualdad y el ascenso de los populismos en Costa Rica
Authors: Cabezas-Barrientos Gustavo 
Published: September 2021

A las puertas del bicentenario de la independencia, el modelo económico que se ha asumido como nación, no parece cumplir las promesas que ha hecho al menos no para la mayoría, sino para un pequeño grupo. A pesar de las múltiples pruebas de la necesidad de un Estado que reactive la economía, ya que el mercado carece del interés, y la necesidad de hacer un mejor reparto de la riqueza; la población no tiene claro en qué consistieron las reformas neoliberales en la década de 1980 y su responsabilidad en el actual Estado social.
Estas reformas han generado varias crisis: económica, institucional, migratoria y de representación política, que han erosionado la institucionalidad y representan el ascenso de grupos que se inclinan a los populismos, en el caso de Costa Rica, en grupos conservadores; donde paradójicamente se añora el Estado de bienestar y se vota por aquellos partidos que prometen su recuperación mediante elementos antidemocráticos y violentando derechos humanos. Este ensayo desarrolla el tema descrito.
Stents metálicos autoexpandibles para el manejo endoscópico de las fístulas esofágicas
Authors: Vargas Rubio Rómulo Darío , Costa Barney Valeria Atenea , Ovalle Hernández Alan Felipe 
Published: September 2021

Objetivos: mostrar la eficacia y seguridad de los stents metálicos autoexpandibles para el manejo endoscópico de las fístulas esofágicas.
Materiales y métodos: se evalúo una serie de casos de manera retrospectiva entre el 2007 y el 2017, en los que se manejaron a 11 pacientes con un stent metálico autoexpandible para el manejo de fístula esofágica, en quienes se realizó el diagnóstico por clínica, endoscopia digestiva alta o estudios radiológicos en la unidad de gastroenterología del Hospital Universitario San Ignacio (HUSI) de Bogotá D. C., Colombia.
Resultados: el principal síntoma inicial fue la disnea en 27,3 % de los casos, seguido por tos en un 18,2 %. El hallazgo más frecuentemente encontrado durante el seguimiento fue el derrame pleural en el 36,4 %, se realizó el diagnóstico de fístula en el 45,5 % con esofagograma y el tipo de lesión más reportada fue la fuga en la anastomosis esofagoentérica, con un 45,5 %, seguida de la esofagopleural, con un 36,4 %; y estos pacientes fueron manejados con un stent metálico autoexpandible. En el 100 % hubo éxito técnico y la resolución del defecto se evidenció en el 72,7 % de los casos. La única complicación reportada fue el desplazamiento del stent en el 27,3 %, y en un paciente se requirió el cambio del stent en 3 oportunidades. El promedio de estancia hospitalaria fue de 41,5 días.
Conclusiones: el manejo endoscópico de las fístulas esofagogástricas con stents metálicos autoexpandibles es efectivo y seguro, con una baja tasa de complicaciones.