bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Mitogenome Analysis of Two Native Apple Snail Species (Ampullariidae, Pomacea) from Peruvian Amazon
Authors: Mendivil Alejandro , Ramírez Rina , Morin Jaime , Ramirez Jorge L. , Siccha-Ramirez Raquel , Britzke Ricardo , Rivera Fátima , Ampuero Andre , Oliveros Nilda , Congrains Carlos
Published: September 2023

Apple snails of the genus Pomacea Perry, 1810 (Mollusca: Caenogastropoda: Ampullariidae) are native to the Neotropics and exhibit high species diversity, holding cultural and ecological significance as an important protein source in Peru. However, most genetic studies in Pomacea have focused mostly on invasive species, especially in Southeast Asia, where they are considered important pests. In this study, we assembled and annotated the mitochondrial genomes of two Pomacea species native to the Peruvian Amazon: Pomacea reevei Ampuero & Ramírez, 2023 and Pomacea aulanieri (Deville & Hupé, 1850). The mitogenomes of P. reevei and P. aulanieri comprise 15,660 and 16,096 bp, respectively, and contain the typical 37 genes of the animal mitochondria with a large control region of 292 bp in P. reevei and 524 bp in P. aulanieri—which fall within the range of what is currently known in Pomacea. Comparisons with previously published mitogenomes in Pomacea revealed differences in the overlapping of adjacent genes, the size of certain protein-coding genes (PCGs) and the secondary structure of some tRNAs that are consistent with the phylogenetic relationships between these species. These findings provide valuable insights into the systematics and genomics of the genus Pomacea.
Using High-Throughput Phenotyping Analysis to Decipher the Phenotypic Components and Genetic Architecture of Maize Seedling Salt Tolerance
Authors: Guo Shangjing , Lv Lujia , Zhao Yanxin , Wang Jinglu , Lu Xianju , Zhang Minggang , Wang Ronghuan , Zhang Ying , Guo Xinyu
Published: September 2023

Soil salinization is a worldwide problem that limits agricultural production. It is important to understand the salt stress tolerance ability of maize seedlings and explore the underlying related genetic resources. In this study, we used a high-throughput phenotyping platform with a 3D laser sensor (Planteye F500) to identify the digital biomass, plant height and normalized vegetation index under normal and saline conditions at multiple time points. The result revealed that a three-leaf period (T3) was identified as the key period for the phenotypic variation in maize seedlings under salt stress. Moreover, we mapped the salt-stress-related SNPs and identified candidate genes in the natural population via a genome-wide association study. A total of 44 candidate genes were annotated, including 26 candidate genes under normal conditions and 18 candidate genes under salt-stressed conditions. This study demonstrates the feasibility of using a high-throughput phenotyping platform to accurately, continuously quantify morphological traits of maize seedlings in different growing environments. And the phenotype and genetic information of this study provided a theoretical basis for the breeding of salt-resistant maize varieties and the study of salt-resistant genes.
The Perpetual Pivot: Understanding Care Partner Experiences in Ontario Long-Term Care Homes during the COVID-19 Pandemic
Authors: Kortes-Miller Katherine , Natale Maïa , Wilson Kimberley , Stinchcombe Arne
Published: September 2023

Long-term care homes (LTCHs) were impacted during the COVID-19 pandemic. With their ever-changing conditions and restrictions, care partners’ roles in LTCHs changed drastically. In this cross-sectional study, an electronic survey was used to examine the experiences of care part-ners who were caring for one or more adults in an Ontario LTCH during the pandemic. The survey was circulated through social media (convenience sample) which produced a convenience sample of 81 caregiver participants. Visit characteristics and a comparison in the quality of care in LTCHs was analyzed before the pandemic as well as during the most restrictive times. Visitation lengths and frequencies, other sources of communication such as phone and video calls, and various types of care provided by caregivers such as personal grooming and personal care all decreased significantly during the pandemic. Care partners also reported that the health of their care recipients decreased significantly during restrictive visitation times. Through thematic analysis, we identified three themes: restrictions and changing LTCH conditions created (1) social isolation and an erosion of connection, (2) a communication breakdown, and (3) a lack of person-centered care. Findings from this research can promote the health and wellbeing of residents and care partners within LTCHs.
Exploring Internal Conflicts and Collaboration of a Hospital Home Healthcare Team: A Grounded Theory Approach
Authors: Tai Pei-Chun , Chang Shofang
Published: September 2023

An aging society is on the rise, leading to a variety of caregiving issues. The Taiwanese government has been implementing a home healthcare integration plan since 2015, aimed at integrating and forming interdisciplinary care teams with medical institutions. This study explores the internal conflict factors among hospital home healthcare team members at a district teaching hospital in Taichung, Taiwan, and it seeks a better collaboration model between them. Semi-structured in-depth interviews were conducted with seven hospital home healthcare team members. Data analysis was based on grounded theory, with research quality relying on the triangulation and consistency analysis methods. The results show that “work overload”, “resource overuse”, “inconsistent assessment”, “limited resources”, “communication cost”, and “lack of incentives” are the major conflicts among the team. This study proposed the following collaboration model, including “identifying the internal stakeholders of a home healthcare team” and “the key stakeholders as referral coordinators”, “patient-centered resource allocation”, and “teamwork orientation”. The study recommends that within a teamwork-oriented home healthcare team, its members should proactively demonstrate their role responsibilities and actively provide support to one another. Only through patient-centered resource allocation and mutual respect can the goal of seamless home healthcare be achieved. The content of the research and samples were approved by the hospital ethics committee (REC108-18).
A Comparative Analysis of Patient Profiles and Health Service Utilization between Patent Medicine Vendors and Community Pharmacists in Nigeria
Authors: Adepoju Victor Abiola , Oladimeji Olanrewaju
Published: September 2023

Background: This study examined Nigeria’s socio-demographic profiles and health service utilization patterns of Patent Medicine Vendors (PMVs) and Community Pharmacists (CPs). Method: A cross-sectional study using a structured self-administered questionnaire among 405 retail outlets (322 PMVs and 83 CPs) across 16 Lagos and Kebbi Local Government Areas (LGAs) between June 2020 and December 2020. Results: Results showed that 60.4% were male, 76.3% from Lagos, 58.3% had tertiary education, and 74.1% had medical training. Cough and fever were common symptoms. Significant differences were found in the utilization of STD services (PMVs: 9.2%, CPs: 12.3%, p = 0.03), services by age <15 (PMVs: 54.3, CPs: 61.2, p < 0.001), and utilization by males (PMVs: 50.8, CPs: 47.1, p = 0.013). The study revealed that men visited PMVs more, while CPs used more STI services and childhood visits. Conclusions: The findings suggest that expanding health services among PMVs could target male-dominant diseases, and capacity building of CPs on syndromic STI management could reduce the STI burden.
Barriers Faced by Australian and New Zealand Women When Sharing Experiences of Family Violence with Primary Healthcare Providers: A Scoping Review
Authors: Rathnayake Jayamini Chathurika , Mat Pozian Nadirah , Carroll Julie-Anne , King Julie
Published: September 2023

Despite the Australian Government’s attempts to reduce domestic violence (DV) incidences, impediments within the social and health systems and current interventions designed to identify DV victims may be contributing to female victims’ reluctance to disclose DV experiences to their primary healthcare providers. This scoping review aimed to provide the state of evidence regarding reluctance to disclose DV incidents, symptoms and comorbidities that patients present to healthcare providers, current detection systems and interventions in clinical settings, and recommendations to generate more effective responses to DV. Findings revealed that female victims are reluctant to disclose DV because they do not trust or believe that general practitioners can help them to solve their issues, and they do not acknowledge that they are in an abusive relationship, and are unaware that they are in one, or have been victims of DV. The most common symptoms and comorbidities victims present with are sleep difficulties, substance use and anxiety. Not all GPs are equipped with knowledge about comorbidities signalling cases of DV. These DV screening programs are the most prominent intervention types within Australian primary health services and are currently not sufficiently nuanced nor sensitive to screen with accuracy. Finally, this scoping review provides formative evidence that in order for more accurate and reliable data regarding disclosure in healthcare settings to be collected, gender power imbalances in the health workforce should be redressed, and advocacy of gender equality and the change of social structures in both Australia and New Zealand remain the focus for reducing DV in these countries.
How to Use Lean Thinking for the Optimization of Clinical Pathways: A Systematic Review and a Proposed Framework to Analyze Pathways on a System Level
Authors: Vijverberg Joanna R. G. , Rouppe van der Voort Marc B. V. , van der Nat Paul B. , Mosselman Machteld J. , Rigter Sander , Biesma Douwe H. , van Merode Frits
Published: September 2023

Lean Thinking and clinical pathways are commonly used concepts to improve healthcare. However, little is known on how to use Lean Thinking for the optimization of pathways or the quantification of both concepts. This study aims to create a framework to analyze pathways with Lean Thinking on a system level, by quantifying the seven wastes, flow and pull. A systematic literature review was performed. Inclusion criteria were the focus of the article on a well-defined group of patients and studied a pathway optimization with Lean Thinking. Data were extracted on measured outcomes, type of intervention and type of researched pathway. Thirty-six articles were included. No articles described the implementation of the Lean Thinking philosophy or studied the development of their people and partners (“4 P” model). Most articles used process optimization tools or problem-solving tools. The majority of the studies focused on process measures. The measures found in the review were used as input for our suggested framework to identify and quantify wastes, flow, and pull in a clinical pathway. The proposed framework can be used to create an overview of the improvement potential of a pathway or to analyze the level of improvement after an enhancement is introduced to a pathway. Further research is needed to study the use of the suggested quantifications.
Navigating the Impacts of Dementia: The Experience of Male Spousal Carers
Authors: Tolhurst Edward , Weicht Bernhard
Published: September 2023

This article investigates the experience of male spousal carers for women living with dementia. While cultural discourses on care are highly gendered, social scientific research often addresses care relationships in gender-neutral terms. Setting out to address this matter, this qualitative research study incorporated semi-structured joint interviews with 10 couples in which a male spouse cared for a woman with dementia. The aim was to explore how couples negotiate relationships and care following a diagnosis of dementia. The focus of this paper is on the perspectives expressed in these joint interviews by the male carers. A thematic analysis was undertaken to establish the key content of the men’s accounts. Three principal themes were identified: making sense of the condition; treating dementia as a problem to be solved; and engaging with professionals and support. The gendered basis of experience for male carers is explored within these themes, demonstrating how societal norms of masculinity intersect with caring roles. The paper concludes that a nuanced research approach to dementia care must continue to be developed, accounting for how gender shapes personal responses to the navigation of care relationships. Practitioners and policymakers must also consider how gendered experience shapes the identities and strategies of male carers.
Mediation of Self-Compassion on Pathways from Stress and Anxiety to Depression among Portuguese Higher Education Students
Authors: Serrão Carla , Valquaresma Andreia , Rodrigues Ana Rita , Duarte Ivone
Published: September 2023

Higher education is a context that requires students to develop academic, social and institutional tasks. As a result of this complex and multidimensional process, students tend to experience greater stress, anxiety and depression, making it crucial for students to mobilize a set of essential personal, social and instrumental resources, for a more positive adaptation to the academic context. Self-compassion is an adaptative emotion-regulation strategy and may help students to better adjust to academic issues. The purpose of this study was to investigate the role of self-compassion as a mediator in the relationship between anxiety and depression, as well as stress and depression. Methods: A cross-sectional study was conducted using an online questionnaire distributed through social media. Stress and anxiety were found to be positively related to depression scores and negatively related to self-compassion. A bootstrapped mediation model confirmed the existence of a significant positive partial mediation effect exerted by self-compassion on the relationship between stress and depression (b = 0.12, 95% CI [0.05, 0.18]). The analysis also showed a significant positive partial mediation effect exerted by self-compassion in the relationship between anxiety and depression (b = 0.13, 95% CI [0.08, 0.18]). Conclusions: Self-compassion might partially mediate the relationship between stress and depression and between anxiety and depression. Findings underscore self-compassion as a potentially protective factor against negative psychological symptoms.
Prevalence and Characteristics of Sexual Victimization among Gay and Bisexual Men: A Preliminary Study in Spain
Authors: Calvet Xavier , Cantera Leonor M.
Published: September 2023

Sexual violence is an understudied issue in the population of gay and bisexual men, although the existing articles to date demonstrate that it is a problem that merits public attention. This study aims to approach the problem of invisibility around the matter, as well as presenting a number of variables that have been usually overlooked in Spanish research or have not been assessed at all. Lifetime sexual victimization, sociodemographic characteristics, situational characteristics and social support were examined among 550 gay and bisexual males living in Spain using a self-administrated questionnaire. Results analysis show that 90.00% (87.18–92.38%) of participants reported at least one experience of unwanted insinuation, 87.27% (84.19–89.94%) reported at least one experience of sexual coercion, 64.00% (59.83–68.02%) reported at least one experience of sexual assault, and specifically 19.82% (16.57–23.40%) reported being raped during their lifetime. Significant differences have been found between some categories regarding gender identity, sexual orientation, age, race/ethnicity and educational level. Overall, these results showcase sexual violence as a pervasive problem in the Spanish gay and bisexual community.
The Genome-Wide Identification of Stable Internal Reference Genes Related to Delayed Spoilage for Accurate qRT-PCR Normalization in Ethephon-Treated Pueraria thomsonii Benth.
Authors: Liu Yujia , Li Ya , He Binrong , Yu Baiyin , Liu Boting , Ma Chongjian , Chen Jie , Zhang Tianhua , Zhang Hongrui , Liu Yuanlong , Li Xiang
Published: September 2023

Pueraria thomsonii Benth. is a perennial leguminous vine with medicinal and nutritional value. However, rapid postharvest physiological deterioration (PPD) reduces its quality and market value. To detect gene expression levels, the quantitative reverse transcription polymerase chain reaction (qRT-PCR) technique requires stable internal reference genes (IRGs). Our findings indicated that an ethephon (C2H6ClO3P) treatment delayed PPD in P. thomsonii tuberous roots and an RNA-seq analysis revealed a significant number of differentially expressed genes (DEGs). To find stable IRGs for the further identification of the genes associated with delayed PPD in P. thomsonii, eight candidate IRGs of the tuberous roots were screened and assessed using qRT-PCR. The expression stability of these genes was determined and ranked using five different algorithms, including NormFinder, BestKeeper, ΔCt, GeNorm, and ReFinder. Consequently, we identified two genes, PtUBC10 and PtACT7, as the best candidate IRGs for qRT-PCR normalization in P. thomsonii, both exposed to ethephon treatment and in different tissues. Moreover, PtUBC10 was found to be the most stably expressed IRG of P. thomsonii during the ethephon treatment. The findings of this investigation furnish significant insights for future gene expression analyses concerning the delay of PPD via ethephon administration, which could also be used in other tuberous plants.
Factors Associated with the Usefulness of Public Health Communication in the Context of COVID-19: Lessons Learned from the African, Caribbean, and Black Communities in Ottawa, Ontario
Authors: Etowa Josephine , Ghose Bishwajit , Etowa Egbe , Dabone Charles , Luc Malemo , Jacques Amoy , Roelofs Susan , Unachukwu Ubabuko , Brown-Shreves Danielle , Osandatuwa Glory , Inoua Haoua
Published: September 2023

Public health communication is critical for promoting behaviours that can prevent the transmission of COVID-19. However, there are concerns about the effectiveness of public health communication within Canada’s African, Caribbean, and Black (ACB) communities. In the community sample of ACB people in Ottawa, Ontario, we asked community members if they perceive public health message related to COVID-19 to be effective. Using this question, the current study aimed to explore factors associated with the perceived usefulness of public health messages related to COVID-19. Results from the multivariate analysis have shown that ACB people with lower levels of risk perception for COVID-19 were less likely to perceive that public health messages were useful (OR = 0.405, p < 0.01). In addition, mistrust in government COVID-19 information was also negatively associated with their perception that health messages are useful (OR = 0.169, p < 0.01). For socioeconomic status, ACB people with no high school diploma (OR = 0.362, p < 0.05) and income dissatisfaction (OR = 0.431, p < 0.05) were less likely to report the perceived usefulness compared to those with a bachelor’s degree and income satisfaction. Based on these findings, we discussed implications for policymakers and directions for future research.
Analysis of COVID-19 Case Demographics and Disease Outcomes in Gary, Indiana
Authors: Sabir Maryam , Al-Tarshan Yazan , Snapp Cameron , Brown Martin , Walker Roland , Han Amy , Kostrominova Tatiana
Published: September 2023

Background: The COVID-19 pandemic further exposed the prevalence of existing health disparities in Black communities in the U.S. The current study evaluates COVID-19 data collected in Gary, Indiana, from June 2020 to June 2021. We hypothesized that the number of COVID-19 cases, hospitalizations, and deaths were influenced by race and income. Methods: In collaboration with the Gary Health Department (GHD), we analyzed demographic data on COVID-19-positive cases. Results: Compared to Gary’s non-Black population, age- and population-adjusted rates of hospitalizations and deaths in the Black population were 3-fold (p < 0.0001) and 2-fold (p < 0.05) higher, respectively. This is despite a higher infection rate (p < 0.0001) in the non-Black population. The median household income of a zip code was negatively correlated with COVID-19 hospitalizations (R2 = 0.6345, p = 0.03), but did not correlate with infections and deaths. Conclusions: The current study demonstrates clear health disparities of income and race in the context of COVID-19-related infections and outcomes in the city of Gary. Indiana University School of Medicine Northwest and GHD officials can collaborate to utilize these data for the reallocation of resources and health education efforts in Gary’s highly populated, low-income, and predominantly Black neighborhoods. It should also prompt further investigation into national health resource allocation.
Physical Activity and Exercise Experience in Spanish and US Men with Fibromyalgia: A Qualitative Cross-Cultural Study
Authors: Montesó-Curto Pilar , Toussaint Loren , Kueny Angela , Ruschak Ilga , Lunn Shannon , Rosselló Lluís , Campoy Carme , Clark Stephanie , Luedtke Connie , Gonçalves Alessandra Queiroga , Martín Carina Aguilar , Vincent Ann , Mohabbat Arya B.
Published: September 2023

Physical exercise is an indispensable element in the multidisciplinary treatment of fibromyalgia syndrome (FMS). The present study examined if men diagnosed with FMS engaged in any type of physical activity or exercise, the perceived effects from exercise, and who specifically recommended exercise. A qualitative cross-cultural study was performed in fibromyalgia clinical units in Spain and the United States. A total of 17 participants, 10 men from Spain and 7 men from the US, were included. In Spain, a focus group was completed in two parts, one month apart in 2018. In the US, five individual interviews and one joint interview with two men were completed in 2018. Three central themes appeared in the qualitative data: (1) Understanding what constitutes physical activity or exercise, (2) Facilitating or discouraging the performance of physical exercise, and (3) Effects of physical activity or exercise on psychological and social symptoms. The actual practice of exercise by patients with FMS is often perceived as leading to pain and fatigue, rather than a treatment facilitator. Physical activity and exercise can provide benefits, including relaxation, socialization, and increased muscle tone. However, minor opioids limit physical activity as they cause addiction, drowsiness, and decrease physical activity in Spanish men. Recommendations in a clinical setting should incorporate exercise as well as physical activity via daily life activities.
Geospatial Analysis in Web Browsers—Comparison Study on WebGIS Process-Based Applications
Authors: Netek Rostislav , Pohankova Tereza , Bittner Oldrich , Urban Daniel
Published: September 2023

With the rapid development of internet technologies in recent years, the shift from the desktop to the web platform can be seen within geospatial analysis. While analytical tools, such as buffer or clip, are routinely used in desktop environments, WebGIS deals with geographic information, including geospatial analysis, within the online environment. The main aim of this paper is to perform a comparison and evaluation of vector-oriented online geoprocessing tools in a WebGIS environment, supported by the development of a custom solution for geospatial analysis. The application called GeOnline is developed and tested as a case study to demonstrate the availability of spatial analysis tools within the web browser. It implements the specialized geospatial library Turf.js, which allows using non-trivial geospatial analysis, such as intersect, clip or calculate centroids. It handles client-side processes. Both a functionality comparison and performance testing are carried out, while the paper primarily focuses on data-driven (data-based) analysis and not only on visual-driven (visual-based) analysis. The comparative study evaluates five geospatial tools (ArcGIS Online, GISCloud, CARTO, FOURSQUARE, GeOnline) and summarizes the solutions from different aspects, including the number of supported operations. Finally, performance tests on GeOnline separately and among alternative solutions are performed. While ArcGIS Online is considered the most comprehensive solution on the market, GeOnline performs well compared to alternative solutions.
Administration of Recombinant TAPBPL Protein Ameliorates Collagen-Induced Arthritis in Mice
Authors: Zhang Zhenzhen , Zhao Jin , Lai Kuan Chen , Lai Laijun
Published: September 2023

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease distinguished by synovial hyperplasia and a progressive destruction of joints. T cells are critical players in the pathogenesis of RA. We have previously identified a novel immune checkpoint molecule, TAPBPL, that inhibits T cell functions in vitro. As a model for human RA, we investigated the ability of the TAPBPL protein to ameliorate collagen type II (CII)-induced arthritis (CIA) in mice that were injected with recombinant TAPBPL or a control protein. The mice were analyzed for CIA development, immune cells, and their responses. We found that TAPBPL protein significantly decreased CIA incidence and reduced clinical and pathological arthritis scores, which were related to a lower number of activated CD4 T cells but a greater number of regulatory T cells (Tregs) in the spleen, and a reduction of Th1/Th17 inflammatory cytokines in the joints and serum. Importantly, TAPBPL protein inhibited CII-specific T cell growth and Th1 and Th17 cytokine expression and reduced the production of CII autoantibodies in the serum. Our results suggest that TAPBPL protein can ameliorate CIA in mice and has the potential to be used in the treatment of patients with RA.
Phase-Controlled Multi-Dimensional-Structure SnS/SnS2/CdS Nanocomposite for Development of Solar-Driven Hydrogen Evolution Photocatalyst
Authors: Jeong Rak Hyun , Lee Jae Hyeong , Boo Jin-Hyo
Published: September 2023

The quest for water-splitting photocatalysts to generate hydrogen as a clean energy source from two-dimensional (2D) materials has enormous implications for sustainable energy solutions. Photocatalytic water splitting, a major field of interest, is focused on the efficient production of hydrogen from renewable resources such as water using 2D materials. Tin sulfide and tin disulfide, collectively known as SnS and SnS2, respectively, are metal sulfide compounds that have gained attention for their photocatalytic properties. Their unique electronic structures and morphological characteristics make them promising candidates for harnessing solar energy for environmental and energy-related purposes. CdS/SnS/SnS2 photocatalysts with two Sn phases (II and IV) were synthesized using a solvothermal method in this study. CdS was successfully placed on a broad SnS/SnS2 plane after a series of characterizations. We found that it is composited in the same way as a core-shell shape. When the SnS/SnS2 phase ratio was dominated by SnS and the structure was composited with CdS, the degradation efficiency was optimal. This material demonstrated high photocatalytic hydrogenation efficiency as well as efficient photocatalytic removal of Cr(VI) over 120 min. Because of the broad light absorption of CdS, the specific surface area, which is the reaction site, became very large. Second, it served as a transport medium for electron transfer from the conduction band (CB) of the SnS to the CB of the SnS2. Because of the composite, these electrons flowed into the CB of CdS, improving the separation efficiency of the photogenerated carriers even further. This material, which was easily composited, also effectively prevented mineral corrosion, which is a major issue with CdS.
Cell Metabolism Therapy by Small Natural Compounds
Authors: Nesci Salvatore , Spagnoletta Anna , Oppedisano Francesca
Published: September 2023

Cellular metabolism therapy counteracting metabolic dysfunction performs a preeminent role in the pathophysiology of different diseases, such as cancer, diabetes, metabolic syndrome, and cardiovascular and neurodegenerative diseases [...]
USP7 Inhibition Suppresses Neuroblastoma Growth via Induction of p53-Mediated Apoptosis and EZH2 and N-Myc Downregulation
Authors: Le Clorennec Christophe , Lee Karen , Huo Yuchen , Zage Peter E.
Published: September 2023

Neuroblastoma (NB) is a pediatric malignancy originating from neural crest cells of the sympathetic nervous system that accounts for 15% of all pediatric cancer deaths. Despite advances in treatment, high-risk NB remains difficult to cure, highlighting the need for novel therapeutic approaches. Ubiquitin-specific protease 7 (USP7) is a deubiquitinase that plays a critical role in tumor suppression and DNA repair, and USP7 overexpression has been associated with tumor aggressiveness in a variety of tumors, including NB. Therefore, USP7 is a potential therapeutic target for NB. The tumor suppressor p53 is a known target of USP7, and therefore reactivation of the p53 pathway may be an effective therapeutic strategy for NB treatment. We hypothesized that inhibition of USP7 would be effective against NB tumor growth. Using a novel USP7 inhibitor, Almac4, we have demonstrated significant antitumor activity, with significant decreases in both cell proliferation and cell viability in TP53 wild-type NB cell lines. USP7 inhibition in NB cells activated the p53 pathway via USP7 and MDM2 degradation, leading to reduced p53 ubiquitination and increased p53 expression in all sensitive NB cells. In addition, USP7 inhibition led to decreased N-myc protein levels in both MYCN-amplified and -nonamplified NB cell lines, but no correlation was observed between MYCN amplification and treatment response. USP7 inhibition induced apoptosis in all TP53 wild-type NB cell lines. USP7 inhibition also induced EZH2 ubiquitination and degradation. Lastly, the combination of USP7 and MDM2 inhibition showed enhanced efficacy. Our data suggests that USP7 inhibition may be a promising therapeutic strategy for children with high-risk and relapsed NB.
Mitochondrial Dynamics and Insulin Secretion
Authors: Kabra Uma D. , Jastroch Martin
Published: September 2023

Mitochondria are involved in the regulation of cellular energy metabolism, calcium homeostasis, and apoptosis. For mitochondrial quality control, dynamic processes, such as mitochondrial fission and fusion, are necessary to maintain shape and function. Disturbances of mitochondrial dynamics lead to dysfunctional mitochondria, which contribute to the development and progression of numerous diseases, including Type 2 Diabetes (T2D). Compelling evidence has been put forward that mitochondrial dynamics play a significant role in the metabolism-secretion coupling of pancreatic β cells. The disruption of mitochondrial dynamics is linked to defects in energy production and increased apoptosis, ultimately impairing insulin secretion and β cell death. This review provides an overview of molecular mechanisms controlling mitochondrial dynamics, their dysfunction in pancreatic β cells, and pharmaceutical agents targeting mitochondrial dynamic proteins, such as mitochondrial division inhibitor-1 (mdivi-1), dynasore, P110, and 15-oxospiramilactone (S3).
Probiotics Modulate Host Immune Response and Interact with the Gut Microbiota: Shaping Their Composition and Mediating Antibiotic Resistance
Authors: Mousa Walaa K. , Mousa Sara , Ghemrawi Rose , Obaid Dana , Sarfraz Muhammad , Chehadeh Fadia , Husband Shannon
Published: September 2023

The consortium of microbes inhabiting the human body, together with their encoded genes and secreted metabolites, is referred to as the “human microbiome.” Several studies have established a link between the composition of the microbiome and its impact on human health. This impact spans local gastrointestinal inflammation to systemic autoimmune disorders and neurodegenerative diseases such as Alzheimer’s and Autism. Some of these links have been validated by rigorous experiments that identify specific strains as mediators or drivers of a particular condition. Consequently, the development of probiotics to compensate for a missing beneficial microbe(s) has advanced and become popular, especially in the treatment of irritable bowel diseases and to restore disrupted gut flora after antibiotic administration. The widespread use of probiotics is often advocated as a natural ecological therapy. However, this perception is not always accurate, as there is a potential for unexpected interactions when administering live microbial cultures. Here, we designed this research to explore the intricate interactions among probiotics, the host, and microbes through a series of experiments. Our objectives included assessing their immunomodulatory effects, response to oral medications, impact on microbial population dynamics, and mediation of antibiotic resistance. To achieve these goals, we employed diverse experimental protocols, including cell-based enzyme -linked immunosorbent assay (ELISA), antibiotic susceptibility testing, antimicrobial activity assays, computational prediction of probiotic genes responsible for antibiotic resistance, polymerase chain reaction (PCR)-based validation of predicted genes, and survival assays of probiotics in the presence of selected oral medications. Our findings highlight that more than half of the tested probiotics trigger an inflammatory response in the Caco-2 cell line, are influenced by oral medications, exhibit antibacterial activity, and possess genes encoding antimicrobial resistance. These results underscore the necessity for a reevaluation of probiotic usage and emphasize the importance of establishing regulations to govern probiotic testing, approval, and administration.
Effects of Clostridium butyricum on Intestinal Microflora and Metabolism of Eriocheir sinensis
Authors: Gao Xiaoning , Liu Xueting , Wang Yali , Wang Tianwei , Fang Di , Hu Kun
Published: September 2023

Clostridium butyricum, a new probiotic in recent years, can produce butyric acid and short-chain fatty acids. It has the characteristics of strong acid and alkali resistance, high temperature resistance, and strong resistance to most antibiotics, and has more advantages than other probiotics. However, the action mechanism of C. butyricum on Eriocheir sinensis is still unclear and needs further study. In this study, when C. butyricum was added to the basic diet, the number of living bacteria was 0, 1 × 106 and 1 × 108 CFU/g, respectively. The E. sinensis were randomly divided into three groups: (blank control group, experimental group 1 (1 × 106 CFU/g) and experimental group 2 (1 × 108 CFU/g)). They were fed an experimental diet for 28 days. The effects of C. butyricum on E. sinensis were studied by detecting the differences in non-specific immune indexes, intestinal microflora, and metabolites between serum and hepatopancreas. The results showed that C. butyricum could improve the antioxidant ability of E. sinensis serum and hepatopancreas, protect intestinal tissues, and promote the absorption of nutrients. At the same time, it can enhance the microbial diversity and richness of the E. sinensis gut flora. LC-MS metabolomics was used to detect the metabolism of intestinal flora. It was found that C. butyricum could up-regulate lysophosphatidylcholine in the intestine. Through the KEGG enrichment pathway, it was found that significantly different metabolites were mainly concentrated in six metabolic pathways. The purine metabolism and alanine, aspartate, and glutamate metabolism pathways showed a downward trend, indicating that the addition of C. butyricum to feed could reduce purine metabolism, promote the water-salt balance of the organism’s cells, and reduce inflammation. In this study, it was found that the addition of certain concentrations of C. butyricum to feed could improve the antioxidant ability of E. sinensis, improve the intestinal flora environment, and promote the growth of beneficial bacteria in the gut. This can promote the body’s metabolism, which is more conducive to its growth.
rs71327024 Associated with COVID-19 Hospitalization Reduces CXCR6 Promoter Activity in Human CD4+ T Cells via Disruption of c-Myb Binding
Authors: Uvarova Aksinya N. , Stasevich Ekaterina M. , Ustiugova Alina S. , Mitkin Nikita A. , Zheremyan Elina A. , Sheetikov Savely A. , Zornikova Ksenia V. , Bogolyubova Apollinariya V. , Rubtsov Mikhail A. , Kulakovskiy Ivan V. , Kuprash Dmitry V. , Korneev Kirill V. , Schwartz Anton M.
Published: September 2023

Single-nucleotide polymorphism rs71327024 located in the human 3p21.31 locus has been associated with an elevated risk of hospitalization upon SARS-CoV-2 infection. The 3p21.31 locus contains several genes encoding chemokine receptors potentially relevant to severe COVID-19. In particular, CXCR6, which is prominently expressed in T lymphocytes, NK, and NKT cells, has been shown to be involved in the recruitment of immune cells to non-lymphoid organs in chronic inflammatory and respiratory diseases. In COVID-19, CXCR6 expression is reduced in lung resident memory T cells from patients with severe disease as compared to the control cohort with moderate symptoms. We demonstrate here that rs71327024 is located within an active enhancer that augments the activity of the CXCR6 promoter in human CD4+ T lymphocytes. The common rs71327024(G) variant makes a functional binding site for the c-Myb transcription factor, while the risk rs71327024(T) variant disrupts c-Myb binding and reduces the enhancer activity. Concordantly, c-Myb knockdown in PMA-treated Jurkat cells negates rs71327024’s allele-specific effect on CXCR6 promoter activity. We conclude that a disrupted c-Myb binding site may decrease CXCR6 expression in T helper cells of individuals carrying the minor rs71327024(T) allele and thus may promote the progression of severe COVID-19 and other inflammatory pathologies.
The Effect of Orally Administered Δ9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD) on Obesity Parameters in Mice
Authors: Eitan Adi , Gover Ofer , Sulimani Liron , Meiri David , Schwartz Betty
Published: September 2023

Prolonged cannabis users show a lower prevalence of obesity and associated comorbidities. In rodent models, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) from the plant Cannabis sativa L. have shown anti-obesity properties, suggesting a link between the endocannabinoid system (ECS) and obesity. However, the oral administration route has rarely been studied in this context. The aim of this study was to investigate the effect of prolonged oral administration of pure THC and CBD on obesity-related parameters and peripheral endocannabinoids. C57BL/6 male mice were fed with either a high-fat or standard diet and then received oral treatment in ramping doses, namely 10 mg/kg of THC or CBD for 5 weeks followed by 30 mg/kg for an additional 5 weeks. Mice treated with THC had attenuated weight gain and improved glucose tolerance, followed by improvement in steatosis markers and decreased hypertrophic cells in adipose epididymal tissue. Mice treated with CBD had improved glucose tolerance and increased markers of lipid metabolism in adipose and liver tissues, but in contrast to THC, CBD had no effect on weight gain and steatosis markers. CBD exclusively decreased the level of the endocannabinoid 2-arachidonoylglycerol in the liver. These data suggest that the prolonged oral consumption of THC, but not of CBD, ameliorates diet-induced obesity and metabolic parameters, possibly through a mechanism of adipose tissue adaptation.
Genetic Landscape of Chronic Myeloid Leukemia and a Novel Targeted Drug for Overcoming Resistance
Authors: Yoshimaru Ryo , Minami Yosuke
Published: September 2023

Tyrosine kinase inhibitors (TKIs) exemplify the success of molecular targeted therapy for chronic myeloid leukemia (CML). However, some patients do not respond to TKI therapy. Mutations in the kinase domain of BCR::ABL1 are the most extensively studied mechanism of TKI resistance in CML, but BCR::ABL1-independent mechanisms are involved in some cases. There are two known types of mechanisms that contribute to resistance: mutations in known cancer-related genes; and Philadelphia-associated rearrangements, a novel mechanism of genomic heterogeneity that occurs at the time of the Philadelphia chromosome formation. Most chronic-phase and accelerated-phase CML patients who were treated with the third-generation TKI for drug resistance harbored one or more cancer gene mutations. Cancer gene mutations and additional chromosomal abnormalities were found to be independently associated with progression-free survival. The novel agent asciminib specifically inhibits the ABL myristoyl pocket (STAMP) and shows better efficacy and less toxicity than other TKIs due to its high target specificity. In the future, pooled analyses of various studies should address whether additional genetic analyses could guide risk-adapted therapy and lead to a final cure for CML.
Whole-Exome Sequencing in a Family with an Unexplained Tendency for Venous Thromboembolism: Multicomponent Prediction of Low-Frequency Variant Deleteriousness and of Individual Protein Interaction
Authors: Lunghi Barbara , Ziliotto Nicole , Balestra Dario , Rossi Lucrezia , Della Valle Patrizia , Pignatelli Pasquale , Pinotti Mirko , D’Angelo Armando , Marchetti Giovanna , Bernardi Francesco
Published: September 2023

Whole-exome sequencing (WES) in families with an unexplained tendency for venous thromboembolism (VTE) may favor detection of low-frequency variants in genes with known contribution to hemostasis or associated with VTE-related phenotypes. WES analysis in six family members, three of whom affected by documented VTE, filtered for MAF < 0.04 in 192 candidate genes, revealed 22 heterozygous (16 missense and six synonymous) variants in patients. Functional prediction by multi-component bioinformatics tools, implemented by a database/literature search, including ClinVar annotation and QTL analysis, prioritized 12 missense variants, three of which (CRP Leu61Pro, F2 Asn514Lys and NQO1 Arg139Trp) were present in all patients, and the frequent functional variants FGB Arg478Lys and IL1A Ala114Ser. Combinations of prioritized variants in each patient were used to infer functional protein interactions. Different interaction patterns, supported by high-quality evidence, included eight proteins intertwined in the “acute phase” (CRP, F2, SERPINA1 and IL1A) and/or in the “fibrinogen complex” (CRP, F2, PLAT, THBS1, VWF and FGB) significantly enriched terms. In a wide group of candidate genes, this approach highlighted six low-frequency variants (CRP Leu61Pro, F2 Asn514Lys, SERPINA1 Arg63Cys, THBS1 Asp901Glu, VWF Arg1399His and PLAT Arg164Trp), five of which were top ranked for predicted deleteriousness, which in different combinations may contribute to disease susceptibility in members of this family.
Correlates of Functional Impairment in Patients with the Behavioral Variant of Frontotemporal Dementia: A PRISMA-Compliant Systematic Review
Authors: Chatzidimitriou Electra , Ioannidis Panagiotis , Aretouli Eleni , Papaliagkas Vasileios , Moraitou Despina
Published: September 2023

The behavioral variant of frontotemporal dementia (bvFTD) has a devastating effect on multiple domains of daily living. The purpose of this PRISMA-compliant systematic review is to summarize the most important factors associated with functional impairment in this clinical group by critically analyzing the existing literature spanning the period from 2000 to 2023. To be included in the review, a study had to investigate any kind of correlates of functional status in bvFTD patients, using a previously validated instrument of functional assessment. Out of 40 articles assessed for eligibility, 18 met the inclusion criteria. The anatomical pattern of cerebral atrophy at baseline appeared to be the strongest predictor of the rate of functional decline over time, with the frontal-dominant anatomical subtype being associated with a faster rate of functional impairment. Additionally, executive dysfunction as well as apathy appeared to contribute significantly to functional disability in bvFTD patients. A comparative examination of bvFTD in relation to other clinical subtypes of FTD and other types of dementia in general suggests that it is the predominant atrophy of the frontal lobes along with the subsequent unique combination of cognitive and neuropsychiatric manifestations that account for the pronounced functional limitations observed in these individuals, even from the early stages of the disease.
New Formulation of Platelet-Rich Plasma Enriched in Platelet and Extraplatelet Biomolecules Using Hydrogels
Authors: Mercader Ruiz Jon , Beitia Maider , Delgado Diego , Sánchez Pello , Arnaiz María Jesús , López de Dicastillo Leonor , Benito-Lopez Fernando , Basabe-Desmonts Lourdes , Sánchez Mikel
Published: September 2023

Platelet-rich plasma (PRP) is an autologous biologic product used in several fields of medicine for tissue repair due to the regenerative capacity of the biomolecules of its formulation. PRP consists of a plasma with a platelet concentration higher than basal levels but with basal levels of any biomolecules present out of the platelets. Plasma contains extraplatelet biomolecules known to enhance its regenerative properties. Therefore, a PRP containing not only a higher concentration of platelets but also a higher concentration of extraplatelet biomolecules that could have a stronger regenerative performance than a standard PRP. Considering this, the aim of this work is to develop a new method to obtain PRP enriched in both platelet and extraplatelet molecules. The method is based on the absorption of the water of the plasma using hydroxyethyl acrylamide (HEAA)-based hydrogels. A plasma fraction obtained from blood, containing the basal levels of platelets and proteins, was placed in contact with the HEAA hydrogel powder to absorb half the volume of the water. The resulting plasma was characterized, and its bioactivity was analyzed in vitro. The novel PRP (nPRP) showed a platelet concentration and platelet derived growth factor (PDGF) levels similar to the standard PRP (sPRP), but the concentration of the extraplatelet growth factors IGF-1 (p < 0.0001) and HGF (p < 0.001) were significantly increased. Additionally, the cells exposed to the nPRP showed increased cell viability than those exposed to a sPRP in human dermal fibroblasts (p < 0.001) and primary chondrocytes (p < 0.01). In conclusion, this novel absorption-based method produces a PRP with novel characteristics compared to the standard PRPs, with promising in vitro results that could potentially trigger improved tissue regeneration capacity.
Revisiting Assessment of Computational Methods for Hi-C Data Analysis
Authors: Yang Jing , Zhu Xingxing , Wang Rui , Li Mingzhou , Tang Qianzi
Published: September 2023

The performances of algorithms for Hi-C data preprocessing, the identification of topologically associating domains, and the detection of chromatin interactions and promoter–enhancer interactions have been mostly evaluated using semi-quantitative or synthetic data approaches, without utilizing the most recent methods, since 2017. In this study, we comprehensively evaluated 24 popular state-of-the-art methods for the complete end-to-end pipeline of Hi-C data analysis, using manually curated or experimentally validated benchmark datasets, including a CRISPR dataset for promoter–enhancer interaction validation. Our results indicate that, although no single method exhibited superior performance in all situations, HiC-Pro, DomainCaller, and Fit-Hi-C2 showed relatively balanced performances of most evaluation metrics for preprocessing, topologically associating domain identification, and chromatin interaction/promoter–enhancer interaction detection, respectively. The comprehensive comparison presented in this manuscript provides a reference for researchers to choose Hi-C analysis tools that best suit their needs.