bluuebunny/crossref_metadata_2025_split huggingface dataset:
Current and future therapeutic strategies for high-grade gliomas leveraging the interplay between epigenetic regulators and kinase signaling networks
Authors: Stitzlein Lea M. , Adams Jack T. , Stitzlein Erin N. , Dudley Richard W. , Chandra Joya 
Published: January 2024

AbstractTargeted therapies, including small molecule inhibitors directed against aberrant kinase signaling and chromatin regulators, are emerging treatment options for high-grade gliomas (HGG). However, when translating these inhibitors into the clinic, their efficacy is generally limited to partial and transient responses. Recent studies in models of high-grade gliomas reveal a convergence of epigenetic regulators and kinase signaling networks that often cooperate to promote malignant properties and drug resistance. This review examines the interplay between five well-characterized groups of chromatin regulators, including the histone deacetylase (HDAC) family, bromodomain and extraterminal (BET)-containing proteins, protein arginine methyltransferase (PRMT) family, Enhancer of zeste homolog 2 (EZH2), and lysine-specific demethylase 1 (LSD1), and various signaling pathways essential for cancer cell growth and progression. These specific epigenetic regulators were chosen for review due to their targetability via pharmacological intervention and clinical relevance. Several studies have demonstrated improved efficacy from the dual inhibition of the epigenetic regulators and signaling kinases. Overall, the interactions between epigenetic regulators and kinase signaling pathways are likely influenced by several factors, including individual glioma subtypes, preexisting mutations, and overlapping/interdependent functions of the chromatin regulators. The insights gained by understanding how the genome and epigenome cooperate in high-grade gliomas will guide the design of future therapeutic strategies that utilize dual inhibition with improved efficacy and overall survival.
Improving access to family planning for women with disabilities in Kaduna city, Nigeria: study protocol for a pragmatic cluster-randomized controlled trial with integrated process evaluation
Authors: Marks Sarah , Arogundade Ekundayo , Carew Mark T. , Chen Shanquan , Banks Lena Morgon , Kuper Hannah , Adegoke Femi , Davey Calum 
Published: January 2024

Abstract
Background
Globally, women with disabilities are less likely to have access to family planning services compared to their peers without disabilities. However, evidence of effective interventions for promoting their sexual and reproductive health and rights remains limited, particularly in low- and middle-income settings. To help address disparities, an inclusive sexual and reproductive health project was developed to increase access to modern contraceptive methods and reduce unmet need for family planning for women of reproductive age with disabilities in Kaduna city, Nigeria. The project uses demand-side, supply-side and contextual interventions, with an adaptive management approach. This protocol presents a study to evaluate the project’s impact.

Methods
A pragmatic cluster-randomized controlled trial design with surveys at baseline and endline will be used to evaluate interventions delivered for at least 1 year at health facility and community levels in comparison to ‘standard’ state provision of family planning services, in the context of state-wide and national broadcast media and advocacy. Randomization will be conducted based on the health facility catchment area, with 19 clusters in the intervention arm and 18 in the control arm. The primary outcome measure will be access to family planning. It was calculated that at least 950 women aged 18 to 49 years with disabilities (475 in each arm) will be recruited to detect a 50% increase in access compared to the control arm. For each woman with disabilities enrolled, a neighbouring woman without disabilities in the same cluster and age group will be recruited to assess whether the intervention has a specific effect amongst women with disabilities. The trial will be complemented by an integrated process evaluation. Ethical approval for the study has been given by the National Health Research Ethics Committee of Nigeria and London School of Hygiene & Tropical Medicine.

Discussion
Defining access to services is complex, as it is not a single variable that can be measured directly and need for family planning is subjectively defined. Consequently, we have conceptualized ‘access to family planning’ based on a composite of beliefs about using services if needed.

Trial registration
ISRCTN registry ISRCTN12671153. Retrospectively registered on 17/04/2023.
Disentangling detrimental sand fly-mite interactions in a closed laboratory sand fly colony: implications for vector-borne disease studies and guidelines for overcoming severe mite infestations
Authors: Nzelu Chukwunonso O. , Meneses Claudio , Bowhay Christina , Coutinho-Abreu Iliano V. , Bennett Emily , Bahrami Somayeh , Bonilla Brian , Kamhawi Shaden , Valenzuela Jesus G. , Peters Nathan C. 
Published: January 2024

Abstract
Background
Vector sand fly colonies are a critical component of studies aimed at improving the understanding of the neglected tropical disease leishmaniasis and alleviating its global impact. However, among laboratory-colonized arthropod vectors of infectious diseases, the labor-intensive nature of sand fly rearing coupled with the low number of colonies worldwide has generally discouraged the widespread use of sand flies in laboratory settings. Among the different factors associated with the low productivity of sand fly colonies, mite infestations are a significant factor. Sand fly colonies are prone to infestation by mites, and the physical interactions between sand flies and mites and metabolites have a negative impact on sand fly larval development.

Methods
Mites were collected from sand fly larval rearing pots and morphologically identified using taxonomic keys. Upon identification, they were photographed with a scanning electron microscope. Several mite control measures were adopted in two different laboratories, one at the Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases-National Institutes of Health (Rockville, MD, USA), and the other at the University of Calgary (Calgary, AB, Canada).

Results
The mite species associated with sand fly colonies in the two laboratories were morphologically identified as Tyrophagus sp. and Stratiolaelaps scimitus. While complete eradication of mites in sand fly colonies is considered unrealistic, drastically reducing their population has been associated with higher sand fly productivity.

Conclusions
We report a case of detrimental interaction between sand flies and Tyrophagus sp. and S. scimitus in a closed laboratory sand fly colony, discuss their impact on sand fly production and provide guidelines for limiting the mite population size in a closed laboratory colony leading to improved sand fly yields.

Graphical abstract
Unveiling a classical mutant in the context of the GH3 β-glucosidase family in Neurospora crassa
Authors: Zhang Yuxin , Nada Basant , Baker Scott E. , Evans James E. , Tian Chaoguang , Benz J. Philipp , Tamayo Elisabeth 
Published: January 2024

AbstractClassical fungal mutant strains obtained by mutagenesis have helped to elucidate fundamental metabolic pathways in the past. In the filamentous fungus Neurospora crassa, the gluc-1 strain was isolated long ago and characterized by its low level of β-glucosidase activity, which is essential for the degradation of cellulose, the most abundant biopolymer on Earth and the main polymeric component of the plant cell wall. Based on genomic resequencing, we hypothesized that the causative mutation resides in the β-glucosidase gene gh3-3 (bgl6, NCU08755). In this work, growth patterns, enzymatic activities and sugar utilization rates were analyzed in several mutant and overexpression strains related to gluc-1 and gh3-3. In addition, different mutants affected in the degradation and transport of cellobiose were analyzed. While overexpression of gh3-3 led to the recovery of β-glucosidase activity in the gluc-1 mutant, as well as normal utilization of cellobiose, the full gene deletion strain Δgh3-3 was found to behave differently than gluc-1 with lower secreted β-glucosidase activity, indicating a dominant role of the amino acid substitution in the point mutated gh3-3 gene of gluc-1. Our results furthermore confirm that GH3-3 is the major extracellular β-glucosidase in N. crassa and demonstrate that the two cellodextrin transporters CDT-1 and CDT-2 are essential for growth on cellobiose when the three main N. crassa β-glucosidases are absent. Overall, these findings provide valuable insight into the mechanisms of cellulose utilization in filamentous fungi, being an essential step in the efficient production of biorefinable sugars from agricultural and forestry plant biomass.
Screening for hypertension in adults: protocol for evidence reviews to inform a Canadian Task Force on Preventive Health Care guideline update
Authors: Shaver Nicole , Beck Andrew , Bennett Alexandria , Wilson Brenda J. , Garritty Chantelle , Subnath Melissa , Grad Roland , Persaud Navindra , Thériault Guylène , Flemming Jennifer , Thombs Brett D. , LeBlanc John , Kaczorowski Janusz , Liu Peter , Clark Christopher E. , Traversy Gregory , Graham Eva , Feber Janusz , Leenen Frans H. H. , Premji Kamila , Pap Robert , Skidmore Becky , Brouwers Melissa , Moher David , Little Julian 
Published: January 2024

Abstract
Purpose
To inform updated recommendations by the Canadian Task Force on Preventive Health Care on screening in a primary care setting for hypertension in adults aged 18 years and older. This protocol outlines the scope and methods for a series of systematic reviews and one overview of reviews.

Methods
To evaluate the benefits and harms of screening for hypertension, the Task Force will rely on the relevant key questions from the 2021 United States Preventive Services Task Force systematic review. In addition, a series of reviews will be conducted to identify, appraise, and synthesize the evidence on (1) the association of blood pressure measurement methods and future cardiovascular (CVD)-related outcomes, (2) thresholds for discussions of treatment initiation, and (3) patient acceptability of hypertension screening methods. For the review of blood pressure measurement methods and future CVD-related outcomes, we will perform a de novo review and search MEDLINE, Embase, CENTRAL, and APA PsycInfo for randomized controlled trials, prospective or retrospective cohort studies, nested case–control studies, and within-arm analyses of intervention studies. For the thresholds for discussions of treatment initiation review, we will perform an overview of reviews and update results from a relevant 2019 UK NICE review. We will search MEDLINE, Embase, APA PsycInfo, and Epistemonikos for systematic reviews. For the acceptability review, we will perform a de novo systematic review and search MEDLINE, Embase, and APA PsycInfo for randomized controlled trials, controlled clinical trials, and observational studies with comparison groups. Websites of relevant organizations, gray literature sources, and the reference lists of included studies and reviews will be hand-searched. Title and abstract screening will be completed by two independent reviewers. Full-text screening, data extraction, risk-of-bias assessment, and GRADE (Grading of Recommendations Assessment, Development and Evaluation) will be completed independently by two reviewers. Results from included studies will be synthesized narratively and pooled via meta-analysis when appropriate. The GRADE approach will be used to assess the certainty of evidence for outcomes.

Discussion
The results of the evidence reviews will be used to inform Canadian recommendations on screening for hypertension in adults aged 18 years and older.

Systematic review registration
This protocol is registered on PROSPERO and is available on the Open Science Framework (osf.io/8w4tz).
The efficacy of tixagevimab/cilgavimab (Evusheld) in prophylaxis and treatment of COVID-19 in immunocompromised patients: a systematic review and meta-analysis
Authors: Glhoom Shaymaa , Fergany Aya , El-Araby Dina , Abdelkhalek Asmaa A. , Gomaa Asmaa , Zayed Eman O. , Abd-ElGwad Mohamed 
Published: January 2024

Abstract
Background
During the COVID-19 pandemic, some populations, including immunocompromised patients, could not tolerate COVID-19 vaccination or had low responses. Evusheld is a combined neutralizing monoclonal antibody containing tixagevimab and cilgavimab. The World Health Organization (WHO) has approved this combination as pre-exposure prophylaxis (PrEP) and treatment for immunocompromised patients. With the new variant, the (WHO) recommended an increase in dose from 300 to 600 mg with a booster dose after 6 months. The target of this review was to compare the efficacy of the two doses, 300 mg and 600 mg of tixagevimab/cilgavimab (Evusheld) as prophylaxis for higher-risk individuals to reveal if there is a significant difference in efficacy between those two doses of the drug.

Methods
In this study, electronic databases (PubMed, Web of Science core collection, Scopus, and Cochran) were investigated for articles up to 31/12/2022 in English using a well-established search strategy. We included studies conducted in immunocompromised patients (aged ≥ 12 years) (WHO) received Evusheld as prophylaxis or treatment for COVID-19. After excluding studies inconsistent with the selection criteria, 24 were involved, 22 of which were included in the meta-analysis. We analyzed the data by using RevMan 5.4 program software.

Results
In the double-arm subgroup analysis, Evusheld 600 mg, administered as prophylaxis, showed no significant difference in the COVID-19 infection rate, mortality rate, or needed hospitalization rate compared with the dose of 300 mg (p = 0.13, p = 0.29, and p = 0.25, respectively). In the single-arm subgroup analysis, Evusheld 600 mg, administered as prophylaxis, showed a significant decrease in the COVID-19 infection rate and the hospitalization rate compared with the dose of 300 mg (p = 0.0001, p = 0.007, respectively). As a treatment, Evusheld showed a significant decrease in the mortality rate over the placebo group (p = 0.01) in COVID-19 patients.

Conclusion
This result indicated that Evusheld was an effective prophylactic and therapeutic drug for COVID-19 infection, especially for immunocompromised patients, but there was no considerable variation between the high and low doses. Further prospective and randomized controlled trials (RCTs) with increased population sizes are necessary to show the valuable benefit of the high dose of Evusheld in COVID-19 prevention and treatment and to compare the difference between the two doses within adverse events.
Cognitive behavioural therapy for social anxiety disorder in people with bipolar disorder: a case series
Authors: Pavlova Barbara , Warnock-Parkes Emma , Alda Martin , Uher Rudolf , Clark David M. 
Published: January 2024

Abstract
Background
Social anxiety disorder increases the likelihood of unfavourable outcomes in people with bipolar disorder. Cognitive behavioural therapy (CBT) is the first-line treatment for social anxiety disorder. However, people with bipolar disorder have been excluded from the studies that this recommendation is based on.

Method
We completed a case series to obtain initial data on whether CBT is an acceptable, safe, and effective treatment for social anxiety disorder in people with bipolar disorder.

Results
Eleven euthymic participants with bipolar disorder attended up to sixteen treatment and three follow-up sessions of CBT for social anxiety disorder. Participants attended on average 95% of the offered CBT sessions. No adverse events were reported. Participants’ mean score on the Social Phobia Inventory decreased from 46.5 (SD 6.6) before the treatment to 19.8 (SD 11.9) at the end of the sixteen-session intervention and further to 15.8 (SD 10.3) by the end of the 3-month follow-up. This degree of improvement is equivalent to the effect observed in studies of CBT for social anxiety disorder in people without severe mental illness.

Conclusions
This case series provides preliminary evidence that CBT is acceptable, safe, and effective for treating social anxiety disorder in people with bipolar disorder during euthymia. A randomized controlled trial is needed to confirm these findings, and to establish whether treatment for social anxiety disorder improves the course of bipolar disorder.
Gender differences in prevalence and clinical risk factors of suicide attempts in young adults with first-episode drug-naive major depressive disorder
Authors: Zhu Quanfeng , Lang Xiaoe , Zhang Xiang-Yang 
Published: January 2024

Background
Suicide rates in adolescents with major depressive disorder (MDD) change with age and gender. Early adulthood is an important transitional stage between late adolescence and adulthood, in which an individual's mind gradually matures. However, there are fewer studies on prevalence and variables linked to the suicide attempts of young adults with MDD.

Aims
To explore gender differences in the prevalence and risk factors associated with suicide attempts in young adults with first-episode drug-naive MDD.

Method
The Hamilton Rating Scale for Depression (HRSD), Hamilton Rating Scale for Anxiety (HRSA) and Positive Subscale of the Positive and Negative Syndrome Scale (PANSS) were used to assess depression, anxiety and psychotic symptoms respectively and various biochemical indicators were assessed.

Results
Among 293 young adults with first-episode drug-naive MDD, the prevalence of suicide attempts was 15.45% (19/123) for males and 14.12% (24/170) for females. Males with suicide attempts had higher levels of thyroid-stimulating hormone (TSH) and higher PANSS Positive Subscale scores, whereas females with suicide attempts had higher TSH, serum total cholesterol, fasting blood glucose and diastolic blood pressure levels and higher scores on the HRSD, HRSA, PANSS Positive Subscale (all Bonferroni corrected P < 0.05). In males, PANSS Positive Subscale score (B = 0.17, P = 0.03, OR = 1.19, 95% CI 1.02–1.38) was a risk factor for suicide attempts.

Conclusions
There were significant gender differences in the risk factors for suicide attempts in young adults with first-episode drug-naive MDD.
Cancer Radiomic and Perfusion Imaging Automated Framework: Validation on Musculoskeletal Tumors
Authors: Sierra Elvis Duran , Valenzuela Raul , Canjirathinkal Mathew A. , Costelloe Colleen M. , Moradi Heerod , Madewell John E. , Murphy William A. , Amini Behrang 
Published: January 2024

PURPOSE Limitations from commercial software applications prevent the implementation of a robust and cost-efficient high-throughput cancer imaging radiomic feature extraction and perfusion analysis workflow. This study aimed to develop and validate a cancer research computational solution using open-source software for vendor- and sequence-neutral high-throughput image processing and feature extraction. METHODS The Cancer Radiomic and Perfusion Imaging (CARPI) automated framework is a Python-based software application that is vendor- and sequence-neutral. CARPI uses contour files generated using an application of the user's choice and performs automated radiomic feature extraction and perfusion analysis. This workflow solution was validated using two clinical data sets, one consisted of 40 pelvic chondrosarcomas and 42 sacral chordomas with a total of 82 patients, and a second data set consisted of 26 patients with undifferentiated pleomorphic sarcoma (UPS) imaged at multiple points during presurgical treatment. RESULTS Three hundred sixteen volumetric contour files were processed using CARPI. The application automatically extracted 107 radiomic features from multiple magnetic resonance imaging sequences and seven semiquantitative perfusion parameters from time-intensity curves. Statistically significant differences ( P < .00047) were found in 18 of 107 radiomic features in chordoma versus chondrosarcoma, including six first-order and 12 high-order features. In UPS postradiation, the apparent diffusion coefficient mean increased 41% in good responders ( P = .0017), while firstorder_10Percentile ( P = .0312) was statistically significant between good and partial/nonresponders. CONCLUSION The CARPI processing of two clinical validation data sets confirmed the software application's ability to differentiate between different types of tumors and help predict patient response to treatment on the basis of radiomic features. Benchmark comparison with five similar open-source solutions demonstrated the advantages of CARPI in the automated perfusion feature extraction, relational database generation, and graphic report export features, although lacking a user-friendly graphical user interface and predictive model building.
Outcome of Hypofractionated Palliative Radiotherapy Regimens for Patients With Advanced Head and Neck Cancer in Tikur Anbessa Hospital, Ethiopia: A Prospective Cohort Study
Authors: Zingeta Girum Tessema , Worku Yohannes Tesfaye , Awol Munir , Woldetsadik Edom Seife , Assefa Mathewos , Chama Tsion Zebdios , Feyisa Jilcha Diribi , Bedada Hawi Furgassa , Adem Mohammed Ibrahim , Mengesha Tariku , Wong Rebecca 
Published: January 2024

PURPOSE Head and neck cancers (HNCs) are the third most commonly treated cancer with radiation in Ethiopia. Most patients present with advanced stage and are not candidates for curative treatment. The objective of our study is to assess the outcome of hypofractionated palliative radiotherapy (RT) for advanced HNCs in a resource-limited setting. MATERIALS AND METHODS Patients with histology-proven advanced HNC candidates for hypofractionated palliative RT were enrolled. Three regimens were allowed: 44.4 Gy in 12 fractions, 30 Gy in 10 fractions, and 20 Gy in five fractions. Response to treatment was assessed at baseline and at 4 weeks after treatment completion. The Kaplan-Meier curve was used to measure the survival. RESULTS Between January 2022 and January 2023, 52 patients were enrolled and 25 patients were eligible for outcome assessment. Index symptoms include pain, bleeding, dysphagia, respiratory distress, and others in 25, 13, 10, 6, and 17 patients, respectively. Complete relief of the top three symptoms include pain in 52% of patients, hemostasis in 84% of patients, and dysphagia in 30% of patients. Objectively, 64% of patients attained partial response. For 48% of patients, their quality of life (QoL) improved in one parameter of the physical scores. Moreover, 64% of patients showed improvement in three parameters. The global functional score improved in 80% of patients. One patient had grade 3 xerostomia. At the end of the study period, 44% of patients died. The median survival after radiation was 9 months (95% CI, 7.2 to 10.8) CONCLUSION All palliative hypofractionated regimens used were effective in terms of symptom control, tumor response rate, and QoL, and were well tolerated. This makes it appropriate for our setup because the majority of patients require palliation.