bluuebunny/crossref_metadata_2025 huggingface dataset:
Key Features of a Multi-Disciplinary Hospital-Based Rehabilitation Program for Children and Adolescents with Moderate to Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome ME/CFS
Authors: Hiremath Sonya , Doukrou Montserrat , Flannery Halina , Carey Catherine , Gregorowski Anna , Ward Joseph , Hargreaves Dougal , Segal Terry Yvonne
Published: October 2022

Purpose of the study: There is limited published data on treatment or outcomes of children and young people (CYP) with moderate or severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Here, we describe outcomes of moderate and severe ME/CFS in CYP treated in a tertiary adolescent service. This information is useful when planning services for CYP and families affected by moderate/severe ME/CFS and to guide future management trials and commissioning decisions. Study Design: A retrospective review was conducted of medical records of the 27 CYP who received ward-based treatment in 2015. Notes were retrospectively reviewed to assess progress in four markers of wellbeing over the period of treatment: (i) mobility, (ii) education, (iii) sleep and (iv) involvement in social/recreational activities. Results: A total of 23/27 (85%) showed improvement in one or more domains over their period of ward-based therapy. 19/27 (70%) of patients showed improvement in physical ability. In 15/23 patients (65%), there was an improvement in ability to access education, in 12/24 (50%) sleep improved, and 16/27 (59%) demonstrated an improvement in socialising/ability perform recreational activities. Conclusion/Implications: A multidisciplinary hospital-based rehabilitation programme for moderate and severe ME/CFS was associated with improvement in at least one area of wellbeing in 85% of the CYP we reviewed. These data may be used as a baseline to evaluate the impact of other models of delivering care for this patient group. It may be useful when considering other groups such as those affected by Post-COVID Syndrome.
Therapeutic Community Gardening as a Green Social Prescription for Mental Ill-Health: Impact, Barriers, and Facilitators from the Perspective of Multiple Stakeholders
Authors: Wood Carly J. , Polley Marie , Barton Jo L. , Wicks Claire L.
Published: October 2022

The UK government has invested £5.77 million in green social prescribing to prevent and tackle mental ill-health. Therapeutic community gardening, one type of green social prescription, provides a range of health outcomes. However, for increased accessibility, a greater understanding of how it impacts mental health and the facilitators and barriers to referral, uptake, and attendance by individuals with mental health problems is required. We conducted and thematically analysed interviews with thirteen stakeholders including social prescribing link workers and garden staff; and focus groups with twenty garden members. The mechanisms by which therapeutic community gardening were suggested to impact mental health were by engaging members with nature and the outdoors, providing hope for the future and facilitating social support and relationships. Factors facilitating referral, uptake, and attendance included a holistic and person-centred approach, which is flexible around health needs. Barriers included awareness of the full offering of therapeutic community gardens and accessibility, in terms of physical location and waiting lists. Given that nature-based interventions have the potential to protect and enhance population health and offer cost savings through reduced reliance on other health services; overcoming these barriers is key to ensuring that therapeutic community gardening is more widely available as an additional mental health treatment.
Association between Handgrip Strength and the Systemic Immune-Inflammation Index: A Nationwide Study, NHANES 2011–2014
Authors: Wu Dongzhe , Gao Xiaolin , Shi Yongjin , Wang Hao , Wang Wendi , Li Yanbin , Zheng Zicheng
Published: October 2022

(1) Background: The Systemic immune-inflammatory index (SII) has been proven to be an effective biomarker of human immune and inflammatory levels and has prognostic significance for most diseases. Handgrip strength (HGS) is a simple and low-cost strength measurement method, which is not only highly correlated with overall muscle strength but also accurately and reliably predicts the risk of multiple chronic diseases and mortality; (2) Purpose: Association between HGS and the SII is unclear. The purpose of this study was to investigate the association between HGS and the SII in American adults; (3) Methods: We used the data from the 2011–2012 and 2013–2014 cycles of the National Health and Nutrition Examination Survey (NHANES), involving a total of 8232 American adults (aged 18–80 years). The SII was calculated as the Platelet count × Neutrophil count/Lymphocyte count; HGS was recorded as the ratio of the sum of the highest grip-strength values of each hand to body mass index taken as the relative grip strength. A weighted generalized linear regression model and analysis of restricted cubic spline regression, adjusted for confounding factors, were used in this study to assess associations between HGS and the SII in American adults; (4) Results: There was a negative correlation between the HGS and the SII of different sexes (p < 0.05), and there was a significant negative nonlinear relationship between the HGS and the SII in males (p for nonlinear = 0.0035), and the SII showed a downward trend with the increase in the HGS in males (Q2: β = −61.03, p = 0.01; Q3: β = −61.28, p = 0.04, Q4: β = −64.36, p = 0.03, p for trend = 0.04), when the HGS exceeds 3.16, with the HGS increasing, the downward trend of increasing the SII slowed down. The nonlinear relationship between the HGS and the SII in females was not significant (p for nonlinear = 0.1011), and the SII showed a linear downward trend with the increase in the HGS (Q2: β = −24.91, p = 0.25; Q3: β = −62.01, p = 0.03, Q4: β = −74.94, p = 0.03, p for trend = 0.01); (5) Conclusions: HGS is inversely and independently associated with SII levels, and although the limited cubic spline regression analysis showed gender differences, the overall trend of the HGS and the SII in different genders was consistent, with both showing that the SII decreased with increasing the HGS. In addition, HGS has high general applicability based on its ease of measurement; it is possible to understand one’s own grip-strength level through routine grip-strength tests, and to make preliminary predictions on the current level of immunity and inflammation in the body.
Does Environmental Credit Rating Promote Green Innovation in Enterprises? Evidence from Heavy Polluting Listed Companies in China
Authors: Zuo Minxin , Wu Tao
Published: October 2022

Environmental credit rating (ECR) is a novel environmental governance tool proposed by China, but its implementation effect is still unknown. This study analyzed whether it achieves the goal of encouraging green innovation in enterprises. Based on the green patent data of listed companies in heavy polluting industries in China from 2010 to 2018, we constructed a heterogeneous timing difference-in-differences model to empirically study the impact of the ECR policy on green innovation. We find that the policy has significantly promoted heavy polluting enterprises’ green innovation. Moreover, the results passed a series of robustness tests. Importantly, we find that the policy has a positive effect on enterprises’ green innovation through the reputation mechanism and financing mechanism. Furthermore, the incentive effect of the policy varies with enterprise characteristics and regional characteristics: the green innovation effect of the policy is more obvious in large-sized and state-owned companies and companies in regions with low fiscal pressure and a high level of financial development are more likely to induce firms’ green innovation. Our research will be of practical value to China’s environmental management, as well as global value to other countries.
Self-Reported Alcohol Abuse and the Desire to Receive Mental Health Counselling Predict Suicidal Thoughts/Thoughts of Self-Harm among Female Residents of Fort McMurray
Authors: Agyapong Belinda , Shalaby Reham , Eboreime Ejemai , Wei Yifeng , Agyapong Vincent I. O.
Published: October 2022

Suicidal ideation and thoughts of self-harm continue to be challenging public health problems. It is presently unknown what the prevalence and correlates of suicidal thoughts and self-harm are in female residents of Fort McMurray, a city that has endured wildfires, flooding, and the COVID-19 pandemic in the last five years. This study aimed to determine the prevalence and correlates of suicidal ideation and thoughts of self-harm among female residents of Fort McMurray. A cross-sectional study using an online survey questionnaire was used to collect sociodemographic and clinical information from the residents of Fort McMurray between 24 April and 2 June 2021. Suicidal ideation and thoughts of self-harm among females were assessed using the ninth question of the Patient Health Questionnaire-9, a validated screening tool used to assess depression symptoms. Likely generalized anxiety disorder (GAD), major depressive disorder (MDD), post-traumatic stress disorder (PTSD) and low resilience were measured using standardized rating scales. Data were analyzed with SPSS version 25 using chi-squared tests and multivariate logistic regression analysis. Among Fort McMurray residents, 249 accessed the online survey, while 186 ultimately completed it, yielding a survey completion rate of 74.7%. Of these, 159 (85%) were females. After controlling for other variables in the regression model, respondents who expressed a desire to receive mental health counselling were more than seven times more likely to report suicidal ideation and thoughts of self-harm compared to the respondents who did not desire to receive mental health counselling (OR: 7.29; 95% CI: 1.19–44.58). Similarly, respondents who reported having abused alcohol in the past year were nearly four times more likely to report suicidal ideation or thoughts of self-harm compared to the respondents who said they had not abused alcohol in the past year (OR: 3.91; 95% CI: 1.05–14.57). A high prevalence of suicidal thoughts and thoughts of self-harm were reported among female residents of Fort McMurray. Timely access to adequate mental health support should be offered to female residents of communities impacted by multiple natural disasters, particularly residents who self-report alcohol abuse or desire to receive mental health counselling.
Patterns of Socioeconomic Inequities in SDGs Relating to Children’s Well-Being in Thailand and Policy Implications
Authors: Waleewong Orratai , Yueayai Khanuengnij
Published: October 2022

Thailand faces many wealth inequities and child health-related problems. This study aimed to describe Thai child health and determine socioeconomic inequities following the child flourishing index, a tool used to measure children’s wellbeing based on the key relevant Sustainable Development Goals. The data from Thailand Multiple Indicator Cluster Survey 2019 were used to examine five indicators where Thailand had not yet achieved good results. The association of socioeconomic status with the five outcomes was explored using logistic regressions, comparing pseudo R-squared, and population attributable fraction analyses. Household wealth, urbanization, education, and primary language were significantly associated with Thai child health. Over 10% of children under 5 years were stunted and had a low birth weight. Fourteen percent of teenage girls had already become mothers. Living in poor households and rural areas, having a head-of-household who was non-Thai speaking, non-Buddhist, and had a low education were identified as risk factors for children with undernutrition status and low birth weight. However, having a head-of-household who spoke a non-Thai language was a protective factor against teenage mothers and having early marriages. Households with better economic status and education provided significant benefits for children and women’s health. The result of this study calls for public policies and multisectoral actions in the wider social and economic spheres that address the social determinants that span across lives and generations. Furthermore, specific social protection programs should be designed to be accessible by these most vulnerable and disadvantaged people.
Job Insecurity and Intention to Quit: The Role of Psychological Distress and Resistance to Change in the UAE Hotel Industry
Authors: Baquero Asier
Published: October 2022

Hotel organizations today are in a state of constant change due to high competition, the emergence of pandemics, and cyclical economic crises. Hospitality employees are currently affected by job insecurity. The purpose of this research was to investigate the effect of job insecurity on intention to quit among hospitality workers, integrating the mediating effect of psychological distress and resistance to change and their mutual relationship. A total of 312 surveys were completed in four four- and five-star hotels in the UAE (Dubai and Sharjah). The SmartPLS 4 software was used to test the hypotheses in a mediation model with the bootstrapping method. The results showed that all of the direct links were positive and significant, and mediating relationships were confirmed. This study found that job insecurity predicts intention to quit through psychological distress and resistance to change acting as mediators, and these factors themselves also impact significantly on intention to quit. Resistance to change is impacted significantly by job insecurity and psychological distress, which suggests that a deeper approach to employees’ resistance to change should be taken, especially when conducting performance appraisals in the hotel industry, by searching for its roots and aiming to minimize employees’ intention to quit.
Optimizing the Use of Cultivated Land in China’s Main Grain-Producing Areas from the Dual Perspective of Ecological Security and Leading-Function Zoning
Authors: Li Chengxiu , Wang Xiuli , Ji Zhengxin , Li Ling , Guan Xiaoke
Published: October 2022

In order to achieve the coordinated development of ecological protection and cultivated land use, ecological security and cultivated land use functions (CLUFs) in the study area were evaluated by constructing a comprehensive evaluation index system. The leading CLUFs were measured, and it was determined to use the normalized revealed comparative advantage (NRCA) index. The spatial superposition analysis of the ecological security level and the leading CLUFs was carried out to obtain the zoning of the coordinated development of ecological security and cultivated land use, and differentiated utilization strategies were proposed for different zones. The results of this study showed the following: (1) The ecological security level of cultivated land in Yuanyang County can be divided into high, medium, and low security levels, accounting for 30.68%, 43.42%, and 25.9% of the total cultivated land area, respectively. The overall ecological security level is high. (2) The current cultivated land use mainly has a production function, accounting for 38.39% of the total cultivated land area, the leading CLUFs that are 34.16% of the cultivated land are the ecological function, and 27.45% of the cultivated land is the living function. (3) The spatial superposition analysis of the ecological security level and leading CLUFs yielded four zones of cultivated land use enhancement, including a production core zone, and different control strategies were proposed for the different zones. These strategies may help to fully realize the multifunctionality of the cultivated land without compromising ecological protection. Implementing differentiated protection for cultivated land in different use zones can achieve the coordinated development of ecological protection and cultivated land use, thus promoting the sustainable use of cultivated land resources.
Past—Present—Future: Urban Spatial Succession and Transition of Rail Transit Station Zones in Japan
Authors: Zhuang Xinyu , Zhang Li , Lu Jie
Published: October 2022

In today’s environmentally conscious society, advocated by a global point of view, land and building use around rail transit stations have changed in the urbanization process. Promoting urban construction and development centered on rail transit stations not only meets the actual needs of urban sustainable development but is also an important means to guide the development of innovative cities. Therefore, it is meaningful to study the characteristics of urban spatial succession, development rules, and future trends based on this new perspective. We analyzed the relationship between rail transit networks and urban form in Japan using GIS by investigating changes in land and building use around rail transit stations over 30 years in the 1980s, 1990s and 2000s (from 1985–2010) using factor analysis and cluster analysis, and we discussed the impact of land consolidation planning and the setting and site selection of new stations based on urban development to understand the development trends inside and outside station zones and urban spatial succession. The results showed the following: (1) There are certain relationships between the development of urban form and traffic demand, and the rail transit network in Japan has the characteristics of high accessibility and aggregation of a small network; (2) Commercial development with a high plot ratio is dispersed and diverted by high-density rail transit stations in the commercial center of Japan; and (3) Commercial sub-centers form complexes by integrating multi-line transfers and form regional linkages through clustered commercial development. Regional business centers realize the agglomeration and radiation of functions through the compound development of station zones. This case study on rail transit zones and urban spatial succession in Japan has important enlightenment significance for urban construction toward optimizing the location and development of suburban rail transit lines, promoting the compact development of cities, exploring new ways to build more reasonable transport, planning city design and layout for rail transit station zones, and providing decision-making references for urban regeneration and sustainable development.
Pre-Diagnosis Health Seeking Behaviors and Experiences Post-Diagnosis, among Men Diagnosed with Tuberculosis in a District of Gauteng Metropolitan City, South Africa: In-Depth Interviews
Authors: Makgopa Sewele , Cele Lindiwe P. , Mokgatle Mathildah M.
Published: October 2022

Background: Tuberculosis remains the number one killer among infectious diseases in South Africa. The TB disease burden is said to be higher among males, 1.6 times more than females in 2018. Moreover, men are reported to have poor healthcare-seeking behaviors. Loss in social and physical functioning, including reduced sexual desires and changes in family life, have been reported following a TB diagnosis. This study explored the meaning that male TB patients attach to their TB diagnosis and impact of TB infection in their lives and those of the people living with them. Methods: This exploratory qualitative study was conducted among 25 participants recruited among male patients seeking TB care from two clinics in informal settlements of the city of Johannesburg. In-depth interviews with open-ended questions were conducted using an audio recorder for the collection of data. Data analysis was conducted on the NVivo version 12 software following an inductive thematic approach. Results: The ages of the participants ranged between 18 and 61 years. Most were unemployed, and only a few were married or in steady relationships. From the two emerging themes, pre-TB diagnosis health-seeking behaviors and post TB-diagnosis experiences, several subthemes were identified. For the former theme, the subthemes include, seeking help from community-based healers and self-medicating, waiting for some period to see if the alternative medicine or treatment worked, taking time to visit a healthcare facility, triggers to seek healthcare, and symptoms reported on presentation to the healthcare facility. The post-TB diagnosis subthemes include making sense of the TB diagnosis, context of disclosing the TB status, fear of social exclusion and experiences of stigma, support received during illness, life changes after TB infection and diagnosis, and lessons learned from the TB experience and future healthcare-seeking behavior. Conclusion: Secrecy about the TB diagnosis indicates fear of social exclusion, and this could be due to the highly stigmatized nature of TB. Waiting to see if alternative medication worked, delayed the TB diagnosis, with consequent late initiation of the anti-TB treatment. The life changes experienced post-TB diagnosis affect the quality of life of the participants and their families. The study recommends that these issues be addressed as a priority.
Psychophysiological Stress Status of Soldiers Prior to an Operative Deployment
Authors: Curiel-Regueros Agustín , Fernández-Lucas Jesús , Clemente-Suárez Vicente Javier
Published: October 2022

An anticipatory stress response develops before an internal or external stimulus, which initiates a homeostasis process through a chain of responses that enable human organisms to face different threats, thus allowing them to adapt to a continuous and eliciting environment. In the current research, we analyzed the psychophysiological anticipatory anxiety response of professional soldiers prior to a real mission in an actual theater of operation. Autonomic modulation through the heart rate variability values, muscular strength manifestation, and psychological stress of 53 military personnel of Army Airmobile Forces (age: M = 35.4 years, SD = 5.88 years; height: M = 1.75 m, SD = 6.87 cm; body mass: M = 77.33 kg, SD = 11.95 kg; military duty = 14.44 years, SD = 6.43; military operation experience = 4 months, SD = 4.25 months) and a control group of 33 civil participants were analyzed. The military personnel presented significant differences in some HRV values related to the activation of sympathetic systems. We found that the military personnel presented an anticipatory anxiety response only at an autonomic level, showing an increased sympathetic modulation, but not at a psychological level, since their anxiety levels were not significantly different than those of the control civilians. In addition, this anticipatory anxiety response did not affect muscular strength manifestation, as it presented no significant differences between the military personnel and the control group.
The Influence of Childhood Trauma and Family Functioning on Internet Addiction in Adolescents: A Chain-Mediated Model Analysis
Authors: Hu Manji , Xu Lin , Zhu Wei , Zhang Tingting , Wang Qiang , Ai Zisheng , Zhao Xudong
Published: October 2022

Objective: This study aimed to examine the prevalence of Internet addiction in adolescents, analyze the associations of childhood trauma, systematic family dynamics, and family functioning with Internet addiction, and investigate the mediating chain role of anxiety and depression in the relationship of childhood trauma and family functioning with adolescent Internet addiction. Methods: This was a cross-sectional study in which general sociodemographic data were obtained from 3357 adolescents in grades 6–12 who were assessed using psychometric instruments such as the Childhood Trauma Questionnaire, Young Internet Addiction Test, Systematic Family Dynamics Self-Rating Scale (SSFD), Family Functioning Assessment (FAD), Self-Rating Depression Scale (SDS), and Self-Rating Anxiety Scale (SAS). Results: (1) The prevalence of Internet addiction among adolescents was 26.09% (876/3357). The prevalence of childhood trauma was 54.96% (1845/3357), and the prevalence of Internet addiction was significantly different between adolescents who suffered childhood trauma and those who did not (χ2 = 96.801, ν = 1, p = 0.000). (2) Childhood trauma and various dimensions of systematic family dynamics had a significant negative and positive relationship with poor family functioning and anxiety or depression, respectively. (3) Childhood trauma was a positive predictor of Internet addiction through the chain-mediated effect of anxiety and depression, but there were no direct effects. Poor family functioning was a positive predictor of adolescent Internet addiction, and this positive prediction was augmented by the chain-mediated effect of anxiety and depression. Conclusions: Childhood trauma and poor family functioning or support predicted Internet addiction in adolescents, with anxiety and depression as mediators.
How to Design Greenway on Urban Land Utilization: Linking Place Preference, Perceived Health Benefit, and Environmental Perception
Authors: Shan Weiting , Xiu Chunliang , Meng Yining
Published: October 2022

The rapid urbanization and over-crowded urban environment have caused a serious public health crisis. Numerous studies have found that public green spaces can benefit human health and well-being. Therefore, a short supply or an inappropriate planning of public green spaces would exaggerate the health crisis. For all these reasons, how to create health-promoting greenways in urban areas becomes a critical and pressing challenge for urban sustainability. To address this challenge, we conducted a photograph-survey study of a greenway to examine the relationship between place preference, perceived health benefit, and environmental perception. Through a set of linear regression analysis, we found that: place preference is significantly and positively associated with six specific perceptions, including relaxation when walking alone, cheering of one’s mood, being away from daily life, traffic safety, recovery from stress, and mental fascination. Furthermore, we identified the important environmental perception elements that have significant positive or negative associations with each identified perception; these were carefully planned. This study is an initial effort to examine a critical urban land-use issue: appropriate planning of greenways in the city to promote public health and well-being. The research findings provide strong and clear guidance on planning strategies for urban greenways and shed light on future studies.
Expanding the Mind–Body–Environment Connection to Enhance the Development of Cultural Humility
Authors: Soulé Isabelle , Littzen-Brown Chloé , Vermeesch Amber L. , Garrigues Layla
Published: October 2022

The unique health care needs of diverse individuals and communities are complex. To meet these needs, healthcare professionals are being called upon to alter traditional ways of thinking, perceiving, and acting in order to create more inclusive environments. Research shows that using mindsight, a process that increases both insight and empathy, can enhance an individual’s mind–body-environment connection, increase self-awareness, and promote the development of cultural humility. This paper will discuss the current perspectives on the mind/body/environment connection from a Western lens that may impact the enactment of cultural humility for healthcare providers. Two evidence-based approaches, yoga and forest therapy, are recommended as effective intervention tools in fostering mindsight and cultural humility. Blending traditional cognitive learning with techniques anchored in the physical body may hold promise in supporting the development of mindsight and cultural humility in healthcare education and practice.
Spatio-Temporal Variability of the Impact of Population Mobility on Local Business Sales in Response to COVID-19 in Seoul, Korea
Authors: Koo Hyeongmo , Lee Soyoung , Lee Jiyeong , Cho Daeheon
Published: October 2022

Social distancing is an effective method for controlling the COVID-19 pandemic by decreasing population mobility, but it has also negatively affected local business sales. This paper explores the spatio-temporal impact of population mobility on local business sales in response to COVID-19 in Seoul, South Korea. First, this study examined the temporal variability by analyzing statistical interaction terms in linear regression models. Second, the spatio-temporal variability was captured using Moran eigenvector spatial filtering (MESF)-based spatially varying coefficients (SVC) models with additional statistical interaction terms. Population mobility and local business sales were estimated from public transportation ridership and restaurant sales, respectively, which were both obtained from spatial big datasets. The analysis results show the existence of various relationships between changes in the population mobility and local business sales according to the corresponding period and region. This study confirms the usability of spatial big datasets and spatio-temporal varying coefficients models for COVID-19 studies and provides support for policy-makers in response to infectious disease.
Downregulation of P300/CBP-Associated Factor Protects from Vascular Aging via Nrf2 Signal Pathway Activation
Authors: Qiu Liqiang , Liu Xiaoxiong , Xia Hao , Xu Changwu
Published: October 2022

Increasing evidence has shown that vascular aging has a key role in the pathogenesis of vascular diseases. P300/CBP-associated factor (PCAF) is involved in many vascular pathological processes, but the role of PCAF in vascular aging is unknown. This study aims to explore the role and underlying mechanism of PCAF in vascular aging. The results demonstrated that the expression of PCAF was associated with age and aging, and remarkably increased expression of PCAF was present in human atherosclerotic coronary artery. Downregulation of PCAF could reduce angiotensin II (AngII)-induced senescence of rat aortic endothelial cells (ECs) in vitro. In addition, inhibition of PCAF with garcinol alleviated AngII-induced vascular senescence phenotype in mice. Downregulation of PCAF could alleviate AngII-induced oxidative stress injury in ECs and vascular tissue. Moreover, PCAF and nuclear factor erythroid-2-related factor 2 (Nrf2) could interact directly, and downregulation of PCAF alleviated vascular aging by promoting the activation of Nrf2 and enhancing the expression of its downstream anti-aging factors. The silencing of Nrf2 with small interfering RNA attenuated the protective effect of PCAF downregulation from vascular aging. These findings indicate that downregulation of PCAF alleviates oxidative stress by activating the Nrf2 signaling pathway and ultimately inhibits vascular aging. Thus, PCAF may be a promising target for aging-related cardiovascular disease.
The Contribution of JAK2 46/1 Haplotype in the Predisposition to Myeloproliferative Neoplasms
Authors: Paes Jhemerson , Silva George A. V. , Tarragô Andréa M. , Mourão Lucivana P. de Souza
Published: October 2022

Haplotype 46/1 (GGCC) consists of a set of genetic variations distributed along chromosome 9p.24.1, which extend from the Janus Kinase 2 gene to Insulin like 4. Marked by four jointly inherited variants (rs3780367, rs10974944, rs12343867, and rs1159782), this haplotype has a strong association with the development of BCR-ABL1-negative myeloproliferative neoplasms (MPNs) because it precedes the acquisition of the JAK2V617F variant, a common genetic alteration in individuals with these hematological malignancies. It is also described as one of the factors that increases the risk of familial MPNs by more than five times, 46/1 is associated with events related to inflammatory dysregulation, splenomegaly, splanchnic vein thrombosis, Budd–Chiari syndrome, increases in RBC count, platelets, leukocytes, hematocrit, and hemoglobin, which are characteristic of MPNs, as well as other findings that are still being elucidated and which are of great interest for the etiopathological understanding of these hematological neoplasms. Considering these factors, the present review aims to describe the main findings and discussions involving the 46/1 haplotype, and highlights the molecular and immunological aspects and their relevance as a tool for clinical practice and investigation of familial cases.
Importance of Micromilieu for Pathophysiologic Mineralocorticoid Receptor Activity—When the Mineralocorticoid Receptor Resides in the Wrong Neighborhood
Authors: Griesler Bruno , Schuelke Christin , Uhlig Christian , Gadasheva Yekaterina , Grossmann Claudia
Published: October 2022

The mineralocorticoid receptor (MR) is a member of the steroid receptor family and acts as a ligand-dependent transcription factor. In addition to its classical effects on water and electrolyte balance, its involvement in the pathogenesis of cardiovascular and renal diseases has been the subject of research for several years. The molecular basis of the latter has not been fully elucidated, but an isolated increase in the concentration of the MR ligand aldosterone or MR expression does not suffice to explain long-term pathologic actions of the receptor. Several studies suggest that MR activity and signal transduction are modulated by the surrounding microenvironment, which therefore plays an important role in MR pathophysiological effects. Local changes in micromilieu, including hypoxia, ischemia/reperfusion, inflammation, radical stress, and aberrant salt or glucose concentrations affect MR activation and therefore may influence the probability of unphysiological MR actions. The surrounding micromilieu may modulate genomic MR activity either by causing changes in MR expression or MR activity; for example, by inducing posttranslational modifications of the MR or novel interaction with coregulators, DNA-binding sites, or non-classical pathways. This should be considered when developing treatment options and strategies for prevention of MR-associated diseases.
Single-Cell DNA Methylation Analysis of Chicken Lampbrush Chromosomes
Authors: Nurislamov Artem , Lagunov Timofey , Gridina Maria , Krasikova Alla , Fishman Veniamin
Published: October 2022

DNA methylation is an essential epigenetic regulation mechanism implicated in transcription and replication control, developmental reprogramming, retroelements silencing and other genomic processes. During mammalian development, a specific DNA methylation pattern should be established in germ cells to allow embryonic development. Less is known about germ cell DNA methylation in other species. To close this gap, we performed a single-cell methylome analysis of chicken diplotene oocytes. We comprehensively characterized methylation patterns in these cells, obtained methylation-based chicken genome segmentation and identified oocyte-specific methylated gene promoters. Our data show that despite the formation of specific transcriptionally hyperactive genome architecture in chicken diplotene oocytes, methylation patterns in these cells closely resemble genomic distribution observed in somatic tissues.
TLR4-Pathway-Associated Biomarkers in Subarachnoid Hemorrhage (SAH): Potential Targets for Future Anti-Inflammatory Therapies
Authors: Heinz Rebecca , Schneider Ulf C.
Published: October 2022

Subarachnoid hemorrhage is associated with severe neurological deficits for survivors. Among survivors of the initial bleeding, secondary brain injury leads to additional brain damage. Apart from cerebral vasospasm, secondary brain injury mainly results from cerebral inflammation taking place in the brain parenchyma after bleeding. The brain’s innate immune system is activated, which leads to disturbances in brain homeostasis, cleavage of inflammatory cytokines and, subsequently, neuronal cell death. The toll-like receptor (TLR)4 signaling pathway has been found to play an essential role in the pathophysiology of acute brain injuries such as subarachnoid hemorrhage (SAH). TLR4 is expressed on the cell surface of microglia, which are key players in the cellular immune responses of the brain. The participants in the signaling pathway, such as TLR4-pathway-like ligands, the receptor itself, and inflammatory cytokines, can act as biomarkers, serving as clues regarding the inflammatory status after SAH. Moreover, protein complexes such as the NLRP3 inflammasome or receptors such as TREM1 frame the TLR4 pathway and are indicative of inflammation. In this review, we focus on the activity of the TLR4 pathway and its contributors, which can act as biomarkers of neuroinflammation or even offer potential new treatment targets for secondary neuronal cell death after SAH.
Matrix Metalloproteinase Gene Polymorphisms Are Associated with Breast Cancer in the Caucasian Women of Russia
Authors: Pavlova Nadezhda , Demin Sergey , Churnosov Mikhail , Reshetnikov Evgeny , Aristova Inna , Churnosova Maria , Ponomarenko Irina
Published: October 2022

We conducted this study to explore the association between matrix metalloproteinase (MMP) gene polymorphisms and breast cancer (BC) risk in the Caucasian women of Russia. In total, 358 affected (BC) and 746 unaffected (cancer-free) women were included in this case-control retrospective study. From BC-related genes in previous studies, ten single nucleotide polymorphisms (SNPs) in five MMP genes (MMP1, 2, 3, 8, 9) were genotyped. The BC risk was calculated by logistic regression (to evaluate the SNPs’ independent effects) and model-based multifactor dimensionality reduction (MB-MDR) (to identify SNP–SNP interactions) methods. The allelic variants’ distribution of c.836 A > G (rs17576) and c. 1721 C > G (rs2250889) MMP9 was significantly different between BC and cancer-free women: for G minor alleles, these SNPs manifested disorder protective effects (OR 0.82 and OR 0.67–0.71, respectively, pperm ≤ 0.035). Eleven haplotypes of six SNPs MMP9 were involved in BC risk (nine haplotypes) and protective (two haplotypes) effects. All 10 SNPs of the MMP genes examined were associated with BC within the 13 SNP–SNP interaction simulated models, with a pivotal role of the two-locus (rs17577 × rs3918242) MMP9 epistatic interaction (defined as 1.81% BC entropy within more than 60% of the genetic models). Under in silico bioinformatics, BC susceptibility MMP polymorphic loci are located in functionally active genome regions and impact genes expression and splicing “regulators” in the mammary gland. The biological pathways of BC MMP candidate genes are mainly realized due to metalloendopeptidase activity and extracellular matrix organization (structure, disassembly, metabolic process, etc.). In conclusion, our data show that MMP gene polymorphisms are related to BC susceptibility in the Caucasian women of Russia.
Vitrification of Lepidopteran Embryos—A Simple Protocol to Cryopreserve the Embryos of the Sunflower Moth, Homoeosoma electellum
Authors: Rajamohan Arun , Prasifka Jarrad R. , Rinehart Joseph P.
Published: October 2022

Embryos of the sunflower moth, Homoeosoma electellum (Hulst), were cryopreserved after modification to the method that was previously described for Pectinophora gossipiella. The workflow to develop the protocol consisted of methods to weaken the embryonic chorion followed by the application of various methods to disrupt the sub-chorionic wax layer. These steps were necessary to render the embryos permeable to water and cryoprotectants. Initially, the embryos were incubated at 21° and 24 °C, and the development of the double pigment spots/eyespot and eclosion were tracked every two hours. The embryos at 24 °C showed eyespots as early as 30 h, while in the case of the embryos that were incubated at 21 °C, there was a developmental delay of approximately 20 h. The embryos at 24 °C showed peak eclosion between 55 and 70 h, and the embryos at 21 °C eclosed between 80 and 100 h of development. Estimating this range is crucial for the purposes of stage selection and treatment initiation for cryopreservation protocol development for the embryos. The control hatch percentage at either developmental temperature was >90%, and the sodium hypochloride, 2-propanol and alkane-based treatments reduced the embryo hatchability to <10%. Hence, a modified surfactant—hypochlorite mixture—was used to destabilize the chorion and solubilize the hydrophobic lipid layers. Water permeability assessments using the dye-uptake method show that polysorbate 80 in combination with sodium hypochlorite alone is capable of permeabilizing the embryo as efficiently as sequential hypochlorite—alkane treatments, but with significantly higher hatch rates. A vitrification medium consisting of ethane diol and trehalose was used to dehydrate and load the embryos with the cryoprotective agent. The median hatch rates after vitrification were 10%, and maximum was 23%.
Survival Rate of the Neotropical Stingless Bees Nannotrigona perilampoides and Frieseomelitta nigra after Exposure to Five Selected Insecticides, under Controlled Conditions
Authors: Góngora-Gamboa Cristian , Ruiz-Sánchez Esaú , Ballina-Gómez Horacio S. , González-Moreno Alejandra , Zamora-Bustillos Roberto
Published: October 2022

Insecticides used in agricultural pest management pose survival risks to the stingless bees that forage on crops in tropical and subtropical regions. In the present study, we evaluated, under laboratory conditions, the acute oral toxicity of five selected insecticides (dinotefuran, imidacloprid, flupyradifurone, spirotetramat, and cyantraniliprole) to two species of neotropical stingless bees: Nannotrigona perilampoides and Frieseomelitta nigra. At field recommended doses, dinotefuran, imidacloprid, and flupyradifurone caused the highest mortality in both bee species. These insecticides also caused the largest decrease in the survival rate when exposed to a 10-fold dilution of the field recommended doses. Notably, dinotefuran exerted a high effect even at 100-fold dilution (100% mortality). In contrast, cyantraniliprole had a low effect and spirotetramat was virtually nontoxic. These results suggest that some insecticides used to control sap-sucking insects may have a significant negative impact on the communities of stingless bees.
Mu2e Crystal Calorimeter Readout Electronics: Design and Characterisation
Authors: Atanov Nikolay , Baranov Vladimir , Borrel Leo , Bloise Caterina , Budagov Julian , Ceravolo Sergio , Cervelli Franco , Colao Francesco , Cordelli Marco , Corradi Giovanni , Davydov Yuri , Di Falco Stefano , Diociaiuti Eleonora , Donati Simone , Echenard Bertrand , Ferrari Carlo , Gioiosa Antonio , Giovannella Simona , Giusti Valerio , Glagolev Vladimir , Grancagnolo Francesco , Hampai Dariush , Happacher Fabio , Hitlin David , Martini Matteo , Middleton Sophie , Miscetti Stefano , Morescalchi Luca , Paesani Daniele , Pasciuto Daniele , Pedreschi Elena , Porter Frank , Raffaelli Fabrizio , Saputi Alessandro , Sarra Ivano , Spinella Franco , Taffara Alessandra , Zanetti Anna Maria , Zhu Ren-Yuan
Published: October 2022

The Mu2e experiment at Fermi National Accelerator Laboratory will search for the charged-lepton flavour-violating neutrinoless conversion of negative muons into electrons in the Coulomb field of an Al nucleus. The conversion electron with a monoenergetic 104.967 MeV signature will be identified by a complementary measurement carried out by a high-resolution tracker and an electromagnetic calorimeter, improving by four orders of magnitude the current single-event sensitivity. The calorimeter—composed of 1348 pure CsI crystals arranged in two annular disks—has a high granularity, 10% energy resolution and 500 ps timing resolution for 100 MeV electrons. The readout, based on large-area UV-extended SiPMs, features a fully custom readout chain, from the analogue front-end electronics to the digitisation boards. The readout electronics design was validated for operation in vacuum and under magnetic fields. An extensive radiation hardness certification campaign certified the FEE design for doses up to 100 krad and 1012 n1MeVeq/cm2 and for single-event effects. A final vertical slice test on the final readout chain was carried out with cosmic rays on a large-scale calorimeter prototype.
Treatment of Medication-Related Osteonecrosis of the Jaw (MRONJ) with Er:YaG Laser and Ozone Therapy: A Case Series
Authors: Porcaro Gianluca , Caccianiga Paolo , Bader Ayt Alla , Caccianiga Gianluigi
Published: October 2022

The purpose of this study is to evaluate the efficacy of the combination of ozone gel and Er:YAG laser treatment in respect of medication-related osteonecrosis of the jaw (MRONJ) for normal procedures. Consequently, the following techniques are compared in the study: medical therapy (MT); MT + conservative surgery with rotary/piezoelectric instruments; MT + ozone therapy; MT + surgical treatment + laser Er:YAG; and MT + ozone therapy + surgical treatment + laser Er:YAG. Fifty-seven patients with MRONJ stages I, II, and III were treated. The protocol was different for each group of patients and included MT, the application of an ozone gel, an Er:YAG laser surgery session, conservative surgery with rotary/piezoelectric instruments, or surgical treatment, and then the monitoring of healing for at least 12 months. The protocols were performed once a week until complete recovery. Patients were reassessed weekly for the first month after treatment, monthly for the following quarter, and then every 3 months until the end of one year. The radiographic surveys were carried out 6 and 12 months after the last treatment. All of the patients in Group 4 (treated with medical therapy + ozone therapy + surgical treatment + laser Er:YAG) achieved complete clinical and radiographic recovery (100%) with complete remission of osteonecrosis. The proposed combined treatment of ozone therapy using laser Er:YAG and the MT + surgical treatment allowed us to obtain excellent results in the resolution of MRONJ. This success was explained by a series of characteristics specific to laser technology; in fact, thanks to its photoacoustic, photochemical, photothermal, and photomechanical properties, the laser made it possible to reduce the bacterial load at the intervention site.
Ion Shift Index at the Immediate Post-Cardiac Arrest Period as an Early Prognostic Marker in Out-of-Hospital Cardiac Arrest Survivors
Authors: Kim Boram , Kwon Hyojeong , Kim Sang-Min , Kim June-Sung , Ryoo Seung , Kim Youn-Jung , Kim Won
Published: October 2022

The ion shift index (ISI) is a suggested marker to reflect the magnitude of ischemic damage. This study aimed to investigate the prognostic value of the ISI for predicting poor neurological outcomes at 6 months in comatose out-of-hospital cardiac arrest (OHCA) survivors by comparing it with the OHCA and Cardiac Arrest Hospital Prognosis (CAHP) scores. This observational registry-based cohort study included adult comatose OHCA survivors admitted to a tertiary care hospital in Korea between 2015 and 2021. The ISI was calculated using the serum electrolyte levels obtained within one hour of resuscitation. The primary outcome was poor neurological function (Cerebral Performance Category score of 3–5) at 6 months. Of the 250 OHCA survivors, 164 (65.6%) had poor neurological outcomes. These patients had a higher median ISI than those with good neurological outcomes (4.95 vs. 3.26, p < 0.001). ISI (adjusted odds ratio, 2.107; 95% confidence interval, 1.350–3.288, p = 0.001) was associated with poor neurological outcomes. The prognostic performance of ISI (area under the curve [AUC], 0.859) was similar to that of the OHCA score (AUC, 0.858; p = 0.968) and the CAHP score (AUC, 0.894; p = 0.183). ISI would be a prognostic biomarker for comatose OHCA survivors that is available during the immediate post-cardiac arrest period.