bluuebunny/crossref_metadata_2025 huggingface dataset:
Training-of-trainers program for community health workers involved in an innovative and community-based intervention against malaria among goldminers in the Guiana shield: a quality and effectiveness evaluation
Authors: Carboni Carlotta , Maroto Irene Jimeno , Galindo Muriel , Plessis Lorraine , Lambert Yann , Bardon Teddy , Vreden Stephen , Suárez-Mutis Martha , Bordalo Jane Miller , Douine Maylis , Sanna Alice
Published: January 2024

Introduction

An innovative and community-based intervention is implemented in the Guiana Shield to eliminate malaria among people involved in artisanal and small-scale gold mining. The intervention consists of the distribution of malaria self-management kits to goldminers and the presumptive treatment for individuals at risk of carrying Plasmodium vivax hypnozoites. The intervention is possible owing to community health workers (CHWs) who are previously trained to master all intervention procedures, including health education activities and goldmining training. This study aimed to evaluate the training program provided to CHWs in terms of quality and effectiveness.

Methods

A training-of-trainers program for CHWs has been developed based on the CDC framework. A mixed-method case study was implemented in two steps between February and March 2023. The evaluation was based on a knowledge survey, satisfaction test, observations, and semi-structured interviews. Quantitative and qualitative data were analyzed and triangulated.

Results

A total of 20 CHWs participated in the training and the first-step evaluation. For the second step, four semi-structured interviews were conducted. The Qualitative data showed that group dynamics and adaptations were central elements of a high-quality training program. Quantitative analysis found that CHWs’ satisfaction was elevated (> 4/5 overall), especially regarding format and learning results. Improvements in knowledge level demonstrated good effectiveness (pre-training vs. post-training, p < 0.05). Nevertheless, some difficulties persisted regarding tasks of the intervention procedure, such as informed consent and smartphone application procedures (with an inaccuracy rate of 29.2% and 16.7%, respectively). Further on-the-job training permitted to address these issues. The project team’s previous experience and the Guiana Shield countries’ commitment to the WHO-E-2025-initiative were identified as levers for the quality of the training, while the complexity of the project context was a challenge.

Discussion

High-quality, effective, and appropriate training programs are required for effective and sustainable interventions involving CHW profiles. Training design is a crucial point to address to accomplish quality and effectiveness. The training-of-trainers model has been shown to allow a high level of satisfaction, good learning results, and satisfactory implementation in the field. Initial and continuing training is an indispensable continuum to sustain good practices in the field and CHWs’ motivation. Training evaluation permits standardizing methods and facilitates transferability.
A machine learning model to predict the risk of depression in US adults with obstructive sleep apnea hypopnea syndrome: a cross-sectional study
Authors: Li Enguang , Ai Fangzhu , Liang Chunguang
Published: January 2024

Objective

Depression is very common and harmful in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). It is necessary to screen OSAHS patients for depression early. However, there are no validated tools to assess the likelihood of depression in patients with OSAHS. This study used data from the National Health and Nutrition Examination Survey (NHANES) database and machine learning (ML) methods to construct a risk prediction model for depression, aiming to predict the probability of depression in the OSAHS population. Relevant features were analyzed and a nomogram was drawn to visually predict and easily estimate the risk of depression according to the best performing model.

Study design

This is a cross-sectional study.

Methods

Data from three cycles (2005–2006, 2007–2008, and 2015–2016) were selected from the NHANES database, and 16 influencing factors were screened and included. Three prediction models were established by the logistic regression algorithm, least absolute shrinkage and selection operator (LASSO) algorithm, and random forest algorithm, respectively. The receiver operating characteristic (ROC) area under the curve (AUC), specificity, sensitivity, and decision curve analysis (DCA) were used to assess evaluate and compare the different ML models.

Results

The logistic regression model had lower sensitivity than the lasso model, while the specificity and AUC area were higher than the random forest and lasso models. Moreover, when the threshold probability range was 0.19–0.25 and 0.45–0.82, the net benefit of the logistic regression model was the largest. The logistic regression model clarified the factors contributing to depression, including gender, general health condition, body mass index (BMI), smoking, OSAHS severity, age, education level, ratio of family income to poverty (PIR), and asthma.

Conclusion

This study developed three machine learning (ML) models (logistic regression model, lasso model, and random forest model) using the NHANES database to predict depression and identify influencing factors among OSAHS patients. Among them, the logistic regression model was superior to the lasso and random forest models in overall prediction performance. By drawing the nomogram and applying it to the sleep testing center or sleep clinic, sleep technicians and medical staff can quickly and easily identify whether OSAHS patients have depression to carry out the necessary referral and psychological treatment.
Racial and ethnic disparities in preterm birth: a mediation analysis incorporating mixtures of polybrominated diphenyl ethers
Authors: Wang Zifan , Zhang Cuilin , Williams Paige L. , Bellavia Andrea , Wylie Blair J. , Kannan Kurunthachalam , Bloom Michael S. , Hunt Kelly J. , James-Todd Tamarra
Published: January 2024

Background

Racial and ethnic disparities persist in preterm birth (PTB) and gestational age (GA) at delivery in the United States. It remains unclear whether exposure to environmental chemicals contributes to these disparities.

Objectives

We applied recent methodologies incorporating environmental mixtures as mediators in causal mediation analysis to examine whether racial and ethnic disparities in GA at delivery and PTB may be partially explained by exposures to polybrominated diphenyl ethers (PBDEs), a class of chemicals used as flame retardants in the United States.

Methods

Data from a multiracial/ethnic US cohort of 2008 individuals with low-risk singleton pregnancies were utilized, with plasma PBDE concentrations measured during early pregnancy. We performed mediation analyses incorporating three forms of mediators: (1) reducing all PBDEs to a weighted index, (2) selecting a PBDE congener, or (3) including all congeners simultaneously as multiple mediators, to evaluate whether PBDEs may contribute to the racial and ethnic disparities in PTB and GA at delivery, adjusted for potential confounders.

Results

Among the 2008 participants, 552 self-identified as non-Hispanic White, 504 self-identified as non-Hispanic Black, 568 self-identified as Hispanic, and 384 self-identified as Asian/Pacific Islander. The non-Hispanic Black individuals had the highest mean ∑PBDEs, the shortest mean GA at delivery, and the highest rate of PTB. Overall, the difference in GA at delivery comparing non-Hispanic Black to non-Hispanic White women was −0.30 (95% CI: −0.54, −0.05) weeks. This disparity reduced to −0.23 (95% CI: −0.49, 0.02) and −0.18 (95% CI: −0.46, 0.10) weeks if fixing everyone's weighted index of PBDEs to the median and the 25th percentile levels, respectively. The proportion of disparity mediated by the weighted index of PBDEs was 11.8%. No statistically significant mediation was found for PTB, other forms of mediator(s), or other racial and ethnic groups.

Conclusion

PBDE mixtures may partially mediate the Black vs. White disparity in GA at delivery. While further validations are needed, lowering the PBDEs at the population level might help reduce this disparity.
A first look at childhood abuse in women with obstructive sleep apnea
Authors: Pal Amrita , Martinez Fernando , Wagman Jennifer , Aysola Ravi S. , Shechter Ari , Mysliwiec Vincent , Martin Jennifer L. , Macey Paul M.
Published: January 2024

Study objectives

Women who experienced childhood sexual abuse have higher rates of obesity, a risk factor for obstructive sleep apnea (OSA). We assessed if prior childhood sexual abuse was more common in women with OSA vs. those in the control group, with possible mediation by obesity.

Methods

In a secondary analysis of a larger project, we studied 21 women with OSA (age mean ± SD 59 ± 12 years, body mass index [BMI] 33 ± 8 kg/m2, respiratory event index [REI] 25 ± 16 events/hour, and Epworth Sleepiness Scale [ESS] score 8 ± 5) and 21 women without OSA (age 53 ± 9 years, BMI 25 ± 5 kg/m2, REI [in 7/21 women] 1 ± 1 events/hour, and ESS score, 5 ± 3). We evaluated four categories of trauma (general, physical, emotional, and sexual abuse) with the Early Trauma Inventory Self-Report–Short Form (ETISR-SF). We assessed group differences in trauma scores with independent samples t-tests and multiple regressions. Parametric Sobel tests were used to model BMI as a mediator for individual trauma scores predicting OSA in women.

Results

Early childhood sexual abuse reported on the ETISR-SF was 2.4 times more common in women with vs. without OSA (p = 0.02 for group difference). Other trauma scores were not significantly different between women with and without OSA. However, BMI was a significant mediator (p = 0.02) in predicting OSA in women who experienced childhood physical abuse.

Conclusion

Childhood sexual abuse was more common in women with vs. without OSA. BMI was a mediator for OSA of childhood physical but not sexual abuse. This preliminary hypothesis-generating study suggests that there may be physiological impacts of childhood trauma in women that predispose them to OSA.
The High Energy X-ray Probe (HEX-P): probing accretion onto stellar mass black holes
Authors: Connors Riley M. T. , Tomsick John A. , Draghis Paul , Coughenour Benjamin , Shaw Aarran W. , García Javier A. , Walton Dominic , Madsen Kristin , Stern Daniel , Rodriguez Nicole Cavero , Dauser Thomas , Del Santo Melania , Jiang Jiachen , Krawczynski Henric , Liu Honghui , Neilsen Joseph , Nowak Michael , Pike Sean , Santangelo Andrea , Sridhar Navin , West Andrew , Wilms Jörn
Published: January 2024

Accretion is a universal astrophysical process that plays a key role in cosmic history, from the epoch of reionization to galaxy and stellar formation and evolution. Accreting stellar-mass black holes in X-ray binaries are one of the best laboratories to study the accretion process and probe strong gravity—and most importantly, to measure the angular momentum, or spin, of black holes, and its role as a powering mechanism for relativistic astrophysical phenomena. Comprehensive characterization of the disk-corona system of accreting black holes, and their co-evolution, is fundamental to measurements of black hole spin. Here, we use simulated data to demonstrate how key unanswered questions in the study of accreting stellar-mass black holes will be addressed by the High Energy X-ray Probe (HEX-P). HEX-P is a probe-class mission concept that will combine high spatial resolution X-ray imaging and broad spectral coverage (0.2–80 keV) with a sensitivity superior to current facilities (including XMM-Newton and NuSTAR) to enable revolutionary new insights into a variety of important astrophysical problems. We illustrate the capability of HEX-P to: 1) measure the evolving structures of black hole binary accretion flows down to low (≲ 0.1%) Eddington-scaled luminosities via detailed X-ray reflection spectroscopy; 2) provide unprecedented spectral observations of the coronal plasma, probing its elusive geometry and energetics; 3) perform detailed broadband studies of stellar mass black holes in nearby galaxies, thus expanding the repertoire of sources we can use to study accretion physics and determine the fundamental nature of black holes; and 4) act as a complementary observatory to a range of future ground and space-based astronomical observatories, thus providing key spectral measurements of the multi-component emission from the inner accretion flows of black hole X-ray binaries.
“This is fine”: the impact of blowouts on subsequent game performance in the National Hockey League (NHL)
Authors: Chachad Ravi , Pradhan Sean , Medina Arman P.
Published: January 2024

Blowouts in sports involve large margins of victory or loss between teams and have long been perceived as influencing subsequent performances by athletes, coaches, fans, and other stakeholders. Under the backdrop of the hot hand ph enomenon, the current study explores the impact of blowouts on subsequent game performance in the National Hockey League (NHL). Specifically, we examine the potential carryover of a “hot (or cold) hand” on the subsequent game following a large win or loss. In our study, we defined blowouts as outlying goal differentials for regular season games (i.e., a difference of approximately 6 goals between teams in a single game based on 3 standard deviations from the mean goal differential during the sampled period). Using this criterion, data from 285 games over the 2005–06 to 2018–19 NHL regular seasons were gathered for analysis. We performed a series of multiple regressions using blowout goal differential as the main predictor, adjusting for location of the subsequent game, number of time zones from the home base city, whether the subsequent game was a back-to-back, and winning percentages of the team and opponent. Our results revealed no significant over or under performance by teams that either won through a blowout or those that lost by a blowout. Our findings are consistent with previous work in other and similar sports contexts. Practical applications and future directions for research are discussed.
Healthy people, soils, and ecosystems: uncovering primary drivers in the adoption of regenerative agriculture by US farmers and ranchers
Authors: Frankel-Goldwater Lee , Wojtynia Niko , Dueñas-Ocampo Sebastián
Published: January 2024

As regenerative agriculture grows in popularity, policy and decision-makers have become interested in its practices. Yet, little is known about those factors driving its adoption among farmers and ranchers. To better understand these drivers, we conducted semi-structured interviews with 31 farmers and ranchers across the United States (US) who self-identified as practitioners of regenerative agriculture. In doing so, we asked about relational values, which reflect one’s perspectives around the links between humans and nature. We also asked about economic and environmental drivers for adoption. In the analysis, we used qualitative coding to identify the range of values and factors driving adoption across our sample. We found that 1) improving the health of people, soils, and ecosystems - through farming practices and related social configurations - was a primary driver for adoption, 2) that relative economic privilege, particularly across two extremes - privileged idealism and less privileged necessity - correlated with most drivers for adoption, 3) that a shift away from industrial agriculture was at once a moral, economic, and environmental imperative for many practitioners, and 4) a systems view of social-ecological relationships was seen as a key to adoption and societal transitions. While our sample represents only a narrow segment of the regenerative agriculture movement in the US, our findings can serve as a useful starting point for understanding the drivers for its adoption. Our findings may also inform conversations on regenerative agriculture’s potential to support food-related sustainability transitions. The discussion situates our work amidst sustainable agriculture and social movement studies, questions of equity in food systems transitions, and the benefits of studying values in developing policy-relevant solutions.
Realizing the value of grassland ecosystem services: global practice and its inspiration for the karst desertification control area
Authors: Li Yongyao , Xiong Kangning , Song Shuzhen , Zhang Wenfang
Published: January 2024

The conflict between grassland ecosystem conservation and economic development is an important but challenging question. Realizing the value of ecosystem services (ES) is considered to be a solution for the dual sustainability of ecology and economy. However, there is a lack of systematic understanding of value realization of grassland ES, especially in the karst desertification (KDC) area, which is still at an exploratory stage. We obtained 527 studies from 48 countries in the past 20 years through the Scopus database, and systematically reviewed the current understandings and practices by the content analysis method, and enlightened the inspiration for the grassland in the KDC area. Results showed that: (i) Over the past 20 years, the literature number showed a fluctuating growth trend, and the study areas are mainly concentrated in economically developed countries with rich grassland resources; (ii) Pathways such as grassland management and payment for ecosystem services (PES) are widely used to improve grassland ES and human well-being, and most studies have shown positive effects; (iii) Their performance is significantly impacted by stakeholders, governments, as well as the attributes of ES, and a path of government-led, stakeholder participation and market-oriented operation should be explored; and (iv) There are still some knowledge gaps, such as, uneven distribution of study areas, few effective pathways for realizing the public grassland ES value, and deficient linkage mechanisms of “grassland ES-industry development-economic system feedback-ecosystem protection,” and so on. Based on our findings, we not only make recommendations for the current dilemma of realizing the value of grassland ES, but also put forward the enlightenments to the grassland in the KDC area based on experiences and lessons learned from global practices. The results can provide theoretical guidance for the ecological protection and sustainable development of grasslands in fragile areas.
How does supplementary green light and UV-radiation affect biomass and rutin content in Levisticum officinale?
Authors: Thoma Felix , Schlehuber Dennis , Somborn Annette , Keuter Volkmar
Published: January 2024

Due to several benefits regarding human health, the flavonoid rutin gains interest in nutrition and pharmaceutical industry. In order to satisfy high quality standards during cultivation and the final product, plants are grown increasingly in controlled environments with LED-technology as artificial light source. In this study the effect of various light settings on rutin content and biomass of Levisticum officinale was investigated. For continuous tracking of the biomass during cultivation, RGB-Images were taken. The actual biomass after harvest showed a strong positive correlation with the number of leaf-pixels detected via image processing (R2 = 0.937). Concerning the effect of UV-B radiation on rutin synthesis, time of synthesis was investigated. Two days after UV-B treatment a significant increase in rutin was observed. A short exposure time in combination with a high irradiance of 1 W m2 also showed positive effects on the rutin content in lovage. No significant effect of UV-B light on fresh weight was shown, but the combination of supplementary green light and high total photosynthetic photon flux density (PPFD) resulted in an increase of biomass.
Outcome of eight working dogs with fibrotic myopathy following extracorporeal shockwave and rehabilitation therapy: a case series
Authors: Tsai Frank C. , Alvarez Leilani X.
Published: January 2024

Introduction

Fibrotic myopathy of the gracilis, semitendinosus, and semimembranosus is described primarily in working German Shepherd dogs. The purpose of this case series is to describe the rehabilitation modalities and treatments utilized in working dogs with fibrotic myopathy and the time frame they were able to continue working.

Methods

Medical records of patients with hindlimb lameness that were presented to the Schwarzman Animal Medical Center in New York City from 2012 to 2023 were retrospectively searched. Signalment, history, clinical evaluation, gait analysis, goniometry of stifles, and follow-up evaluation were compared among patients. Ten male working dogs met inclusion criteria. Extracorporeal Shockwave Therapy (ECSWT) was administered under sedation or general anesthesia. Rehabilitation therapy (RT), including massage, hamstring stretch, photobiomodulation, pulsed electromagnetic field therapy, warm compress, therapeutic ultrasound, underwater treadmill, and therapeutic exercises, were performed once every one to 3 weeks with varying protocols according to patient assessments. Follow-up phone calls and emails were conducted to determine long-term outcome.

Results

On average, dogs were able to work full-time for 32.1 months (range 6–82; SD 23.6) from the time of diagnosis. No activity limitation was reported by the owners/handlers.

Discussion

This report is the first to describe non-invasive medical treatments that may extend the working ability of dogs diagnosed with fibrotic myopathy. Further prospective randomized controlled studies are needed to demonstrate the efficacy of ECSWT and RT for treating fibrotic myopathy.

Conclusion

The results of this retrospective study suggest that the combination of ECSWT and RT may allow working dogs with fibrotic myopathy to continue their working capacity for an extended period of time.
Single institution study of the immune landscape for canine oral melanoma based on transcriptome analysis of the primary tumor
Authors: Vanhaezebrouck Isabelle F. , Bakhle Kimaya M. , Mendez-Valenzuela Carlos R. , Lyle L. Tiffany , Konradt Kristoph , Scarpelli Matthew L.
Published: January 2024

Introduction

Understanding a tumor’s immune context is paramount in the fight against cancer. Oral melanoma in dogs serves as an excellent translational model for human immunotherapy. However, additional study is necessary to comprehend the immune landscape of dog oral melanomas, including their similarity to human melanomas in this context.

Methods

This retrospective study utilizes formalin-fixed paraffin-embedded (FFPE) tissue samples to analyze RNA sequences associated with oral melanoma in dogs. Nanostring Technologies was used for conducting RNA sequencing. The focus is on understanding the differences between melanoma tumors restricted to the oral cavity (OL) and the same primary oral tumors with a history of metastasis to the lymph nodes or other organs (OM). Normal buccal mucosa samples are also included as a normal tissue reference.

Results

In the OM patient group, gene signatures exhibit significant changes relative to the OL patient group, including significantly decreased expression of S100, BRAF, CEACAM1, BCL2, ANXA1, and tumor suppressor genes (TP63). Relative to the OL tumors, the OM tumors had significantly increased expression of hypoxia-related genes (VEGFA expression), cell mobility genes (MCAM), and PTGS2 (COX2). The analysis of the immune landscape in the OM group indicates a shift from a possible “hot” tumor suppressed by immune checkpoints (PDL1) to significantly heightened expression not only of those checkpoints but also the inclusion of other immune blockades such as PD1 and IDO2. In addition, the OM group had significantly reduced expression of Toll-like receptors (TLR4) and IL-18 relative to the OL group, contributing to the tumor’s immune escape. Additionally, signs of immune cell exhaustion are evident in both the OM and OL groups through significantly increased expression of TIGIT relative to normal tissue. Both the OM and OL groups had significantly increased expression of the immune cell marker CD4 expression relative to normal tissue. Further, CD4 expression significantly decreased in OM relative to OL; however, this study cannot determine the specific cell types expressing CD4 in OM and OL tumors.

Discussion

This preliminary study reports significant changes in gene expression for oral melanoma between canine patients with localized disease relative to those with metastatic disease. In the future, a more in-depth investigation involving immunohistochemistry analysis and single-cell RNA expression is necessary to confirm our findings.
Increasing Gene Editing Efficiency via CRISPR/Cas9- or Cas12a-Mediated Knock-In in Primary Human T Cells
Authors: Kruglova Natalia , Shepelev Mikhail
Published: January 2024

T lymphocytes represent a promising target for genome editing. They are primarily modified to recognize and kill tumor cells or to withstand HIV infection. In most studies, T cell genome editing is performed using the CRISPR/Cas technology. Although this technology is easily programmable and widely accessible, its efficiency of T cell genome editing was initially low. Several crucial improvements were made in the components of the CRISPR/Cas technology and their delivery methods, as well as in the culturing conditions of T cells, before a reasonable editing level suitable for clinical applications was achieved. In this review, we summarize and describe the aforementioned parameters that affect human T cell editing efficiency using the CRISPR/Cas technology, with a special focus on gene knock-in.
Design and Force/Angle Independent Control of a Bionic Mechanical Ankle Based on an Artificial Muscle Matrix
Authors: Jia Zhikun , Han Guangming , Jin Hu , Xu Min , Dong Erbao
Published: January 2024

Inspired by the natural skeletal muscles, this paper presents a novel shape memory alloy-based artificial muscle matrix (AMM) with advantages of a large output force and displacement, flexibility, and compactness. According to the composition of the AMM, we propose a matrix control strategy to achieve independent control of the output force and displacement of the AMM. Based on the kinematics simulation and experiments, we obtained the output displacement and bearing capacity of the smart digital structure (SDS) and confirmed the effectiveness of the matrix control strategy to achieve force and displacement output independently and controllably. A bionic mechanical ankle actuated by AMM was proposed to demonstrate the actuating capability of the AMM. Experimental results show that the angle and force of the bionic mechanical ankle are output independently and have a significant gradient. In addition, by using a self-sensing method (resistance self-feedback) and PD control strategy, the output angle and force of the bionic mechanical ankle can be maintained for a long time without overheating of the AMM.
Oxidation of Allura Red AC Using the NaHCO3-activated H2O2 System Catalyzed with Cobalt Supported on Al-PILC
Authors: Marín-González Natalia , Giraldo-Loaiza Camila , Macías-Quiroga Iván F. , Rivera-Giraldo Juan D. , Cardona-Castaño Julio A. , Sanabria-González Nancy R.
Published: January 2024

The oxidation of aqueous solutions containing Allura Red AC (AR–AC) using bicarbonate-activated peroxide (BAP) and cobalt-impregnated pillared clay (Co/Al–PILC) as the catalyst was investigated. Using the CCD-RMS approach (central composite design–response surface methodology), the effects of dye, H2O2, and NaHCO3 concentrations on AR–AC degradation were studied. The decolorization, total nitrogen (TN), and total carbon (TC) removals were the analyzed responses, and the experimental data were fitted to empirical quadratic equations for these responses, obtaining coefficients of determination R2 and adjusted-R2 higher than 0.9528. The multi-objective optimization conditions were [dye] = 21.25 mg/L, [H2O2] = 2.59 mM, [NaHCO3] = 1.25 mM, and a catalyst loading of 2 g/L. Under these conditions, a decolorization greater than 99.43% was obtained, as well as TN and TC removals of 72.82 and 18.74%, respectively, with the added advantage of showing cobalt leaching below 0.01 mg/L. Chromatographic analyses (GC–MS and HPLC) were used to identify some reaction intermediates and by-products. This research showed that wastewater containing azo dyes may be treated using the cobalt-catalyzed BAP system in heterogeneous media.
A Typology of Multiple School Leadership
Authors: Cheng Yin-Cheong
Published: January 2024

In facing the challenges of huge transformations in different areas of society, many educators, policy makers, social leaders, researchers and other stakeholders may doubt how schools and their leadership and management remain relevant to and effective for the future of education. Given that multiple school functions are needed to serve society at different levels, the required roles in school leadership are inevitably multiple, diverse and demanding. In past decades, many studies have been conducted with a focus on some aspects of leadership functions and processes. Unfortunately, there is a lack of a typology of school leadership to map out comprehensive leadership profiles and understand their multiple characteristics for leading school development and effectiveness in a fast-changing environment. Based on the framework of multiple school effectiveness, this paper aims to propose a typology of multiple school leadership that can provide a new, comprehensive way to re-conceptualize the multiple nature and characteristics of school leadership in a complicated context. Depending on the rationalities, concerns, actions, outcomes and contexts of leadership in practice, the typology of multiple school leadership may include six models: technological leadership, economic leadership, social leadership, political leadership, cultural leadership, and learning leadership. Within this typology, new possibilities and approaches to school leadership can be drawn for research, practice and development towards the future.
Fractional View Analysis System of Korteweg–de Vries Equations Using an Analytical Method
Authors: Jawarneh Yousef , Alsheekhhussain Zainab , Al-Sawalha M. Mossa
Published: January 2024

This study introduces two innovative methods, the new transform iteration method and the residual power series transform method, to solve fractional nonlinear system Korteweg–de Vries (KdV) equations. These equations, fundamental in describing nonlinear wave phenomena, present complexities due to the involvement of fractional derivatives. In demonstrating the application of the new transform iteration method and the residual power series transform method, computational analyses showcase their efficiency and accuracy in computing solutions for fractional nonlinear system KdV equations. Tables and figures accompanying this research present the obtained solutions, highlighting the superior performance of the new transform iteration method and the residual power series transform method compared to existing methods. The results underscore the efficacy of these novel methods in handling complex nonlinear equations involving fractional derivatives, suggesting their potential for broader applicability in similar mathematical problems.
Effect of Exercise Programs on Physical Performance in Community-Dwelling Older Adults with and without Frailty: Systematic Review and Meta-Analysis
Authors: Flores-Bello Cristina , Correa-Muñoz Elsa , Sánchez-Rodríguez Martha A. , Mendoza-Núñez Víctor Manuel
Published: January 2024

Background: The measurement of physical performance constitutes an indicator of the physical functional capacity of older adults with and without frailty. Aim: To present a synthesis of knowledge on the effect of exercise programs on physical performance in older adults with and without frailty in the community. Method: A systematic review was carried out in accordance with the PRISMA-2020 criteria. The search for articles was made until 4 May 2023 in PubMed, Scopus, Web of Science, Cochrane Library, SciELO and LILACS. The outcome variable was physical performance, measured through the SPPB (Short Physical Performance Battery). The mean difference (MD) was estimated to evaluate the effect. Result: We found 2483 studies, of which 12 met the eligibility criteria for the systematic review and 9 for the meta-analysis. The effect of exercise on SPPB scores was significantly higher in the exercise group compared to control in non-frail older adults with MD = 0.51 [95% CI, 0.05 to 0.96, p < 0.05]. Likewise, in older adults with frailty, the effect of exercise on the global SPPB score was significantly higher in the exercise group compared to the control with MD = 0.66 [95% CI, 0.09 to 1.24, p < 0.05]. Conclusion: Our findings suggest that exercise programs are effective in increasing and/or maintaining physical performance in older adults with and without frailty, whose effect is more evident in older adults with frailty, probably due to the greater margin of recovery of intrinsic capacity. This systematic review shows the differentiated effect of exercise training on physical performance in older adults with and without frailty. Scientific evidence reinforces the importance of implementing physical exercise programs in all older adults, including those who are frail. However, it is necessary to specify the types and doses (duration, frequency and intensity), for individualized groups, previously grouped according to the SPPB score.
Biology and Development of DNA-Targeted Drugs, Focusing on Synthetic Lethality, DNA Repair, and Epigenetic Modifications for Cancer: A Review
Authors: Watanabe Kiyotaka , Seki Nobuhiko
Published: January 2024

DNA-targeted drugs constitute a specialized category of pharmaceuticals developed for cancer treatment, directly influencing various cellular processes involving DNA. These drugs aim to enhance treatment efficacy and minimize side effects by specifically targeting molecules or pathways crucial to cancer growth. Unlike conventional chemotherapeutic drugs, recent discoveries have yielded DNA-targeted agents with improved effectiveness, and a new generation is anticipated to be even more specific and potent. The sequencing of the human genome in 2001 marked a transformative milestone, contributing significantly to the advancement of targeted therapy and precision medicine. Anticipated progress in precision medicine is closely tied to the continuous development in the exploration of synthetic lethality, DNA repair, and expression regulatory mechanisms, including epigenetic modifications. The integration of technologies like circulating tumor DNA (ctDNA) analysis further enhances our ability to elucidate crucial regulatory factors, promising a more effective era of precision medicine. The combination of genomic knowledge and technological progress has led to a surge in clinical trials focusing on precision medicine. These trials utilize biomarkers for identifying genetic alterations, molecular profiling for potential therapeutic targets, and tailored cancer treatments addressing multiple genetic changes. The evolving landscape of genomics has prompted a paradigm shift from tumor-centric to individualized, genome-directed treatments based on biomarker analysis for each patient. The current treatment strategy involves identifying target genes or pathways, exploring drugs affecting these targets, and predicting adverse events. This review highlights strategies incorporating DNA-targeted drugs, such as PARP inhibitors, SLFN11, methylguanine methyltransferase (MGMT), and ATR kinase.
Splicing Modulation via Antisense Oligonucleotides in Recessive Dystrophic Epidermolysis Bullosa
Authors: Hainzl Stefan , Trattner Lisa , Liemberger Bernadette , Bischof Johannes , Kocher Thomas , Ablinger Michael , Nyström Alexander , Obermayer Astrid , Klausegger Alfred , Guttmann-Gruber Christina , Wally Verena , Bauer Johann W. , Hofbauer Josefina Piñón , Koller Ulrich
Published: January 2024

Antisense oligonucleotides (ASOs) represent an emerging therapeutic platform for targeting genetic diseases by influencing various aspects of (pre-)mRNA biology, such as splicing, stability, and translation. In this study, we investigated the potential of modulating the splicing pattern in recessive dystrophic epidermolysis bullosa (RDEB) patient cells carrying a frequent genomic variant (c.425A > G) that disrupts splicing in the COL7A1 gene by using short 2′-O-(2-Methoxyethyl) oligoribo-nucleotides (2′-MOE ASOs). COL7A1-encoded type VII collagen (C7) forms the anchoring fibrils within the skin that are essential for the attachment of the epidermis to the underlying dermis. As such, gene variants of COL7A1 leading to functionally impaired or absent C7 manifest in the form of extensive blistering and wounding. The severity of the disease pattern warrants the development of novel therapies for patients. The c.425A > G variant at the COL7A1 exon 3/intron 3 junction lowers the efficiency of splicing at this junction, resulting in non-functional C7 transcripts. However, we found that correct splicing still occurs, albeit at a very low level, highlighting an opportunity for intervention by modulating the splicing reaction. We therefore screened 2′-MOE ASOs that bind along the COL7A1 target region ranging from exon 3 to the intron 3/exon 4 junction for their ability to modulate splicing. We identified ASOs capable of increasing the relative levels of correctly spliced COL7A1 transcripts by RT-PCR, sqRT-PCR, and ddPCR. Furthermore, RDEB-derived skin equivalents treated with one of the most promising ASOs exhibited an increase in full-length C7 expression and its accurate deposition along the basement membrane zone (BMZ).
Unraveling the Role of RNA-Binding Proteins, with a Focus on RPS5, in the Malignant Progression of Hepatocellular Carcinoma
Authors: Zhou Chongyang , Wu Qiumin , Zhao Haibei , Xie Ruixi , He Xin , Gu Huiying
Published: January 2024

Hepatocellular carcinoma (HCC) represents a major global health concern, demanding a thorough understanding of its molecular mechanisms for effective therapeutic strategies. RNA-binding proteins (RBPs) play critical roles in post-transcriptional gene regulation, with their dysregulation increasingly recognized as a hallmark of various cancers. However, the specific contributions of RBPs to HCC pathogenesis and prevention remain incompletely understood. In this study, we systematically conducted an examination of the expression profiles and clinical relevance of RBPs in 556 clinical samples from well-established cohorts. Through comprehensive analyses, a subset of RBPs exhibiting significant overexpression in HCC was identified, establishing a noteworthy correlation between their aberrant expression and HCC progression. Furthermore, 40S ribosomal protein S5 (RPS5), a ribosomal protein, emerged as a potential key contributor in HCC progression. Rigorous analyses established a correlation between elevated RPS5 expression and advanced clinicopathological features, suggesting its potential as a prognostic biomarker. Experiments further confirmed the impact of RPS5 on pivotal cellular processes implicated in cancer progression, including cell proliferation and metastasis. Further mechanistic studies unveiled the potential of RPS5 to activate the cell cycle by binding to key molecules involved in the pathway, thereby promoting the malignant progression of HCC. Additionally, our analysis of the etiology behind RPS5 overexpression in HCC posited it as an outcome of transcriptional regulation by the transcription factors Nuclear Respiratory Factor 1 (NRF1) and MYC-associated zinc finger protein (MAZ). In conclusion, our study contributes to the growing evidence elucidating the intricate involvement of RBPs, exemplified by RPS5, in the malignant progression of HCC. The integration of genomic, transcriptomic, and functional analyses provides a comprehensive understanding of the regulatory mechanisms associated with RPS5 in HCC. This comprehensive analysis not only advances our knowledge of the molecular drivers behind HCC but also highlights the potential therapeutic relevance of targeting RBPs and their regulatory network for the development of more effective treatment strategies.
Potential Role of Macrophage Polarization in the Progression of Hunner-Type Interstitial Cystitis
Authors: Ko Kwang Jin , Kim Gahyun , Sung Hyun Hwan , Park Woong-Yang , Lee Kyu-Sung
Published: January 2024

Background: Hunner-type interstitial cystitis (HIC) is a chronic inflammatory condition of the bladder. However, it remains unclear whether there is a causal relationship between the presence of Hunner lesions and seemingly normal-appearing areas in the bladder (non-Hunner lesions). This study aimed to investigate the fundamental aspects of HIC by examining potential genetic differences between Hunner and non-Hunner lesions and elucidate their role as potential markers in the progression and suppression of the disease. Methods: This cross-sectional study enrolled patients with HIC (n = 10) who underwent supratrigonal cystectomy along with augmentation cystoplasty. Full-thickness bladder tissue was collected from Hunner and non-Hunner lesions in the same patient. Normal bladder tissue biopsies were also obtained as controls. Whole transcriptome analysis was performed to analyze the gene expression patterns and immune cell populations. Results: The mucosal layers of patients exhibited similar pathway dysregulation across Hunner and non-Hunner lesions, with immunerelated pathways being prominently affected. In the mucosal layer, genes related to anti-inflammatory and immune suppression were downregulated in Hunner lesions compared to non-Hunner lesions. Moreover, in Hunner lesions, genes related to macrophage differentiation and polarization, such as VSIG4, CD68, MAFB, and LIRB4, were downregulated. The cell fraction of M2 macrophages was found to decrease in Hunner lesions. Immunohistochemical staining revealed an elevated fraction of M1 macrophages and a reduced fraction of M2 macrophages in Hunner lesions compared to those in non-Hunner lesions. In the muscular layer, transcriptomic evidence of muscle thickness was observed in both Hunner and non-Hunner lesions; however, the difference was not significant. Conclusion: Hunner lesions showed a reduced expression of anti-inflammatory and immunosuppressive factors compared to non-Hunner lesions, along with alterations in immune cell populations. This study suggests the possibility that macrophage polarization is related to the progression from non-Hunner lesions to Hunner lesions, suggesting its relevance to the characteristics of autoimmune diseases.
Study of the Antibacterial Activity of Superhydrophilic and Superhydrophobic Copper Substrates against Multi-Drug-Resistant Hospital-Acquired Pseudomonas aeruginosa Isolates
Authors: Bondareva Natalia E. , Sheremet Anna B. , Morgunova Elena Y. , Khisaeva Irina R. , Parfenova Alisa S. , Chernukha Marina Y. , Omran Fadi S. , Emelyanenko Alexandre M. , Boinovich Ludmila B.
Published: January 2024

The global spread of multidrug-resistant (MDR) hospital-acquired pathogens is a serious problem for healthcare units. The challenge of the spreading of nosocomial infections, also known as hospital-acquired pathogens, including Pseudomonas aeruginosa, must be addressed not only by developing effective drugs, but also by improving preventive measures in hospitals, such as passive bactericidal coatings deposited onto the touch surfaces. In this paper, we studied the antibacterial activity of superhydrophilic and superhydrophobic copper surfaces against the P. aeruginosa strain PA103 and its four different polyresistant clinical isolates with MDR. To fabricate superhydrophilic and superhydrophobic coatings, we subjected the copper surfaces to laser processing with further chemosorption of fluorooxysilane to get a superhydrophobic substrate. The antibacterial activity of superhydrophilic and superhydrophobic copper surfaces was shown, with respect to both the collection strain PA103 and polyresistant clinical isolates of P. aeruginosa, and the evolution of the decontamination of a bacterial suspension is presented and discussed. The presented results indicate the promising potential of the exploitation of superhydrophilic coatings in the manufacture of contact surfaces for healthcare units, where the risk of infection spread and contamination by hospital-acquired pathogens is extremely high.
Mimicking Protein Kinase C Phosphorylation Inhibits Arc/Arg3.1 Palmitoylation and Its Interaction with Nucleic Acids
Authors: Barylko Barbara , Taylor Clinton A. , Wang Jason , Earnest Svetlana , Stippec Steve , Binns Derk D. , Brautigam Chad A. , Jameson David M. , DeMartino George N. , Cobb Melanie H. , Albanesi Joseph P.
Published: January 2024

Activity-regulated cytoskeleton-associated protein (Arc) plays essential roles in diverse forms of synaptic plasticity, including long-term potentiation (LTP), long-term depression (LTD), and homeostatic plasticity. In addition, it assembles into virus-like particles that may deliver mRNAs and/or other cargo between neurons and neighboring cells. Considering this broad range of activities, it is not surprising that Arc is subject to regulation by multiple types of post-translational modification, including phosphorylation, palmitoylation, SUMOylation, ubiquitylation, and acetylation. Here we explore the potential regulatory role of Arc phosphorylation by protein kinase C (PKC), which occurs on serines 84 and 90 within an α-helical segment in the N-terminal domain. To mimic the effect of PKC phosphorylation, we mutated the two serines to negatively charged glutamic acid. A consequence of introducing these phosphomimetic mutations is the almost complete inhibition of Arc palmitoylation, which occurs on nearby cysteines and contributes to synaptic weakening. The mutations also inhibit the binding of nucleic acids and destabilize high-order Arc oligomers. Thus, PKC phosphorylation of Arc may limit the full expression of LTD and may suppress the interneuronal transport of mRNAs.
Advanced Drug Carriers: A Review of Selected Protein, Polysaccharide, and Lipid Drug Delivery Platforms
Authors: Jamroży Mateusz , Kudłacik-Kramarczyk Sonia , Drabczyk Anna , Krzan Marcel
Published: January 2024

Studies on bionanocomposite drug carriers are a key area in the field of active substance delivery, introducing innovative approaches to improve drug therapy. Such drug carriers play a crucial role in enhancing the bioavailability of active substances, affecting therapy efficiency and precision. The targeted delivery of drugs to the targeted sites of action and minimization of toxicity to the body is becoming possible through the use of these advanced carriers. Recent research has focused on bionanocomposite structures based on biopolymers, including lipids, polysaccharides, and proteins. This review paper is focused on the description of lipid-containing nanocomposite carriers (including liposomes, lipid emulsions, lipid nanoparticles, solid lipid nanoparticles, and nanostructured lipid carriers), polysaccharide-containing nanocomposite carriers (including alginate and cellulose), and protein-containing nanocomposite carriers (e.g., gelatin and albumin). It was demonstrated in many investigations that such carriers show the ability to load therapeutic substances efficiently and precisely control drug release. They also demonstrated desirable biocompatibility, which is a promising sign for their potential application in drug therapy. The development of bionanocomposite drug carriers indicates a novel approach to improving drug delivery processes, which has the potential to contribute to significant advances in the field of pharmacology, improving therapeutic efficacy while minimizing side effects.