bluuebunny/crossref_metadata_2025 huggingface dataset:
Resilience and problematic smartphone use: a moderated mediation model
Authors: Hao Zejun , Jin Liangyi , Huang Jinzi , Akram Hafiza Rabia , Cui Qian
Published: January 2023

Background

Problematic smartphone use (PSU) is adversely correlated with resilience. To completely comprehend the mechanism underlying this relationship, however, more investigation is required.

Methods

For this cross-sectional study, the method of stratified random cluster sampling was applied. 834 Chinese undergraduate students (aged 17 to 24) were recruited, and self-reported questionnaires were administered to measure their levels of resilience, perceived social support, the sense of school belonging, and habitual and problematic smartphone use.

Results

The findings showed that resilience both directly and indirectly predicted PSU through perceived social support and the sense of school belonging. Additionally, there were significant moderating effects of habitual smartphone use between resilience and perceived social support, the sense of school belonging, and PSU.

Conclusions

Our research identified the negative influence of resilience on PSU, and specifically, highlighted the mediation effects of perceived social support and the sense of school belonging. Of significance, we also found the moderation effect of habitual smartphone use in the development of PSU.
Behavioural Change Techniques in Health Coaching-Based Interventions for Type 2 Diabetes: A Systematic Review and Meta-Analysis
Authors: Almulhim Abdullah N. , Hartley Hannah , Norman Paul , Caton Samantha J. , Doğru Onur Cem , Goyder Elizabeth
Published: January 2023

Background

Given the high rates globally of Type 2 Diabetes Mellitus (T2DM), there is a clear need to target health behaviours through person-centred interventions. Health coaching is one strategy that has been widely recognised as a tool to foster positive behaviour change. However, it has been used inconsistently and has produced mixed results. This systematic review sought to explore the use of behaviour change techniques (BCTs) in health coaching interventions and identify which BCTs are linked with increased effectiveness in relation to HbA1C reductions.

Methods

In line with the PICO framework, the review focused on people with T2DM, who received health coaching and were compared with a usual care or active control group on HbA1c levels. Studies were systematically identified through different databases including Medline, Web of science, and PsycINFO searches for relevant randomised controlled trials (RCTs) in papers published between January 1950 and April 2022. The Cochrane collaboration tool was used to evaluate the quality of the studies. Included papers were screened on the reported use of BCTs based on the BCT taxonomy. The effect sizes obtained in included interventions were assessed by using Cohen’s d and meta-analysis was used to estimate sample-weighted average effect sizes (Hedges’ g).

Results

Twenty RCTs with a total sample size of 3222 were identified. Random effects meta-analysis estimated a small-sized statistically significant effect of health coaching interventions on HbA1c reduction (g+ = 0.29, 95% CI: 0.18 to 0.40). A clinically significant HbA1c decrease of ≥5 mmol/mol was seen in eight studies. Twenty-three unique BCTs were identified in the reported interventions, with a mean of 4.5 (SD = 2.4) BCTs used in each study. Of these, Goal setting (behaviour) and Problem solving were the most frequently identified BCTs. The number of BCTs used was not related to intervention effectiveness. In addition, there was little evidence to link the use of specific BCTs to larger reductions in HbA1c across the studies included in the review; instead, the use of Credible source and Social reward in interventions were associated with smaller reductions in HbA1c.

Conclusion

A relatively small number of BCTs have been used in RCTs of health coaching interventions for T2DM. Inadequate, imprecise descriptions of interventions and the lack of theory were the main limitations of the studies included in this review. Moreover, other possible BCTs directly related to the theoretical underpinnings of health coaching were absent. It is recommended that key BCTs are identified at an early stage of intervention development, although further research is needed to examine the most effective BCTs to use in health coaching interventions.

Trial registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021228567.
Obesity at age 20 and weight gain during adulthood increase risk of total and premature all-cause mortality: findings from women attending breast screening in Manchester
Authors: Pegington Mary , Harvie Michelle , Harkness Elaine F. , Brentnall Adam , Malcomson Lee , Southworth Jake , Fox Jill , Howell Anthony , Cuzick Jack , Evans D. Gareth
Published: January 2023

Background

Obesity in early adulthood is associated with lower breast cancer rates in later life. This could be interpreted as a positive reinforcement of excess weight amongst younger women however, the wider implications of higher weights are less well known. This study examined the association between both obesity in early adulthood and body mass index (BMI) change through adulthood, and all-cause mortality.

Methods

The Predicting Risk of Cancer At Screening (PROCAS) study recruited 57,902 women aged 46–73 years (median age 57.2, IQR 51.8–63.7 years) from the Greater Manchester National Health Service breast screening programme in North West England between 2009 and 2015. It was used to assess associations between BMI at 20 years and cohort entry with all-cause mortality ascertained via deaths recorded on the National Breast Screening System to June 2020. Hazard ratios were estimated using proportional hazards (Cox) regression adjusted for factors at entry to the cohort: age, deprivation, bilateral oophorectomy, hormone-replacement therapy, menopausal status, ethnicity, alcohol intake, physical activity, and BMI.

Results

The prevalence of overweight (25–30 kg/m2) and obesity (> 30 kg/m2) were 10.4% and 2.5% respectively at 20 years, increasing to 35.2% and 25.9% respectively at cohort entry. After a mean 8.7 years follow-up we observed that overweight (HR = 1.27, 95%CI = 1.10–1.47) and obesity (HR = 2.11, 95%CI = 1.67–2.66) at 20 years had a higher mortality rate compared with healthy weight. Women who were underweight/healthy weight at 20 years and gained weight to obesity at entry had a slightly increased mortality rate compared with women who were underweight/healthy weight at both time points (HR 1.16, 95%CI = 1.02–1.32). Women with overweight (HR = 1.36, 95%CI = 1.06–1.75) or obesity (HR = 1.90, 95%CI = 1.45–2.48) at both 20 years and entry had a higher mortality rate than women who were underweight/healthy weight at both points.

Conclusions

Women who self-reported overweight and obesity at 20 years had a shorter life expectancy in this cohort of women attending breast cancer screening. Weight gain from 20 years was common in this group. Girls and women should be supported to maintain a healthy weight throughout the lifespan to help increase life expectancy.

Trial registration number NCT04359420, retrospectively registered 24/04/2020.
Cultural beliefs, attitudes and perceptions of lactating mothers on exclusive breastfeeding in The Gambia: an ethnographic study
Authors: Sosseh Sering A. L. , Barrow Amadou , Lu Zxyyann Jane
Published: January 2023

Background

WHO/UNICEF recommends that women in resource-poor developing countries- like the Gambia, should exclusively breastfeed their infants for the first six months of their lives because of its health benefits to both mother and infant. The study aimed to explore the cultural beliefs, attitudes, and perceptions of lactating mothers towards exclusive breastfeeding in The Gambia.

Methods

This was a qualitative ethnographic study of culture-sharing groups of mothers with infants 4 to 6 months old. The study was conducted from July to October 2014 and data collection was done through a face-to-face, in-depth interview and moderate participant observation. The study recruited 22 breastfeeding mothers attending government health facilities in the Kanifing Municipality. The collected data were transcribed verbatim and analyzed through a constant comparison method generating six cultural themes, each with sub-themes.

Results

Baby’s welfare is traditionally based on the types of food mother’s eat. To this end, mothers reportedly shunned eating green leafy vegetables, liquid and hot foods for their infants’ wellbeing. Encounters such as weight loss, nipple inflammation, and backache, which mothers associated with hyper latching and sitting for prolonged breastfeeding, respectively, were among major undesirable physical effects revealed by the participants. Furthermore, the necessity of giving water to infants for their survival was illustrated as a barricade to exclusive breastfeeding practices. Likewise, the entrenched practice of giving charm water to instill the Islamic faith and shielding infants against evil spirits was another factor influencing exclusive breastfeeding practices. Finally, the belief that breast milk adequacy is based on breast size and nurturing men’s physical strength by starting prelacteal feeds early in infancy also contributes to the meek exclusive breastfeeding rate among mothers.

Conclusion

This study could be a gazette piece for effective policy making and enhance nurses’ cultural sensitivity while caring for lactating mothers. Cultural meanings of health care behaviors in lactating mothers challenge universally applying guidelines of exclusive breastfeeding to all societies. The study findings could benefit healthcare providers in informing policies and designing culturally adaptive and acceptable community-based breastfeeding intervention programs in resource-limited settings.
Disruptions of sexually transmitted and blood borne infections testing services during the COVID-19 pandemic: accounts of service providers in Ontario, Canada
Authors: Ryu Heeho , Blaque Ezra , Stewart Mackenzie , Anand Praney , Gómez-Ramírez Oralia , MacKinnon Kinnon R. , Worthington Catherine , Gilbert Mark , Grace Daniel
Published: January 2023

Background

Since the onset of the COVID-19 pandemic in March 2020 in Canada, the availability of sexual health services including sexually transmitted and blood-borne infection (STBBI) testing has been negatively impacted in the province of Ontario due to their designation as “non-essential” health services. As a result, many individuals wanting to access sexual healthcare continued to have unmet sexual health needs throughout the pandemic. In response to this, sexual health service providers have adopted alternative models of testing, such as virtual interventions and self-sampling/testing. Our objective was to investigate service providers’ experiences of disruptions to STBBI testing during the COVID-19 pandemic in Ontario, Canada, and their acceptability of alternative testing services.

Methods

Between October 2020-February 2021, we conducted semi-structured virtual focus groups (3) and in-depth interviews (11) with a diverse group of sexual health service providers (n = 18) including frontline workers, public health workers, sexual health nurses, physicians, and sexual health educators across Ontario. As part of a larger community-based research study, data collection and analysis were led by three Peer Researchers and a Community Advisory Board was consulted throughout the research process. Transcripts were transcribed verbatim and analysed with NVivo software following grounded theory.

Results

Service providers identified the reallocation of public health resources and staff toward COVID-19 management, and closures, reduced hours, and lower in-person capacities at sexual health clinics as the causes for a sharp decline in access to sexual health testing services. Virtual and self-sampling interventions for STBBI testing were adopted to increase service capacity while reducing risks of COVID-19 transmission. Participants suggested that alternative models of testing were more convenient, accessible, safe, comfortable, cost-effective, and less onerous compared to traditional clinic-based models, and that they helped fill the gaps in testing caused by the pandemic.

Conclusions

Acceptability of virtual and self-sampling interventions for STBBI testing was high among service providers, and their lived experiences of implementing such services demonstrated their feasibility in the context of Ontario. There is a need to approach sexual health services as an essential part of healthcare and to sustain sexual health services that meet the needs of diverse individuals.
Recognising the importance of chronic lung disease: a consensus statement from the Global Alliance for Chronic Diseases (Lung Diseases group)
Authors: Gould Gillian Sandra , Hurst John R. , Trofor Antigona , Alison Jennifer A. , Fox Gregory , Kulkarni Muralidhar M. , Wheelock Craig E. , Clarke Marilyn , Kumar Ratika
Published: January 2023

Background

Chronic respiratory diseases are disorders of the airways and other structures of the lung, and include chronic obstructive pulmonary disease (COPD), lung cancer, asthma, bronchiectasis, interstitial lung diseases, occupational lung diseases and pulmonary hypertension. Through this article we take a broad view of chronic lung disease while highlighting (1) the complex interactions of lung diseases with environmental factors (e.g. climate change, smoking and vaping) and multimorbidity and (2) proposed areas to strengthen for better global patient outcomes.

Conclusion

We suggest new directions for the research agenda in high-priority populations and those experiencing health disparities. We call for lung disease to be made a research priority with greater funding allocation globally.
Independent effects of the triglyceride-glucose index on all-cause mortality in critically ill patients with coronary heart disease: analysis of the MIMIC-III database
Authors: Zhang Rongting , Shi Shanshan , Chen Weihua , Wang Yani , Lin Xueqin , Zhao Yukun , Liao Lihua , Guo Qian , Zhang Xiaoying , Li Weiguo , Zhang Kaijun , Liao Ying , Fang Yong
Published: January 2023

Background

The triglyceride-glucose (TyG) index is a reliable alternative biomarker of insulin resistance (IR). However, whether the TyG index has prognostic value in critically ill patients with coronary heart disease (CHD) remains unclear.

Methods

Participants from the Medical Information Mart for Intensive Care III (MIMIC-III) were grouped into quartiles according to the TyG index. The primary outcome was in-hospital all-cause mortality. Cox proportional hazards models were constructed to examine the association between TyG index and all-cause mortality in critically ill patients with CHD. A restricted cubic splines model was used to examine the associations between the TyG index and outcomes.

Results

A total of 1,618 patients (65.14% men) were included. The hospital mortality and intensive care unit (ICU) mortality rate were 9.64% and 7.60%, respectively. Multivariable Cox proportional hazards analyses indicated that the TyG index was independently associated with an elevated risk of hospital mortality (HR, 1.71 [95% CI 1.25–2.33] P = 0.001) and ICU mortality (HR, 1.50 [95% CI 1.07–2.10] P = 0.019). The restricted cubic splines regression model revealed that the risk of hospital mortality and ICU mortality increased linearly with increasing TyG index (P for non-linearity = 0.467 and P for non-linearity = 0.764).

Conclusions

The TyG index was a strong independent predictor of greater mortality in critically ill patients with CHD. Larger prospective studies are required to confirm these findings.
Heat shock protein 27 deficiency promotes ferrous ion absorption and enhances acyl-Coenzyme A synthetase long-chain family member 4 stability to promote glioblastoma cell ferroptosis
Authors: Zhang Kai , Wu Yue , Chen Guangliang , Wang Hao , Liu Yongsheng , Zhou Youxin
Published: January 2023

Background

Glioblastoma is one of the malignant tumors of the central nervous system with high lethality, high disability and low survival rate. Effective induction of its death is one of the existing challenges. In recent studies, heat shock protein 27 (HSP27) has been shown to be associated with ferroptosis; therefore, targeting HSP27 may be a potential therapeutic approach for GBM.

Methods

Immunohistochemistry and western blot analysis were used to detect the expression of HSP27 in GBM tissues. CCK8, plate clone formation assay, EdU proliferation assay for cell proliferation ability, PI, LDH release assay for cell viability. Reactive oxygen, iron levels, and mitochondrial potential for HSP27 silencing were assayed for ferrotosis in vitro. Western blotting and IP were used to verify the relationship between HSP27 and ACSL4. The effect of knockdown of HSP27 on tumor growth capacity was assessed in an intracranial xenograft model.

Results

HSP27 was significantly highly expressed in GBM. In vitro experiments, knockdown of HSP27 significantly induced ferroptosis in GBM cells. IP and western blot demonstrated a sumo-ization link between HSP27 and ACSL4. In vivo experiments, HSP27 deficiency retarded tumor growth rate by promoting ferroptosis.

Conclusions

HSP27 deficiency promotes GBM ferroptosis. Targeting HSP27 may serve as a new direction for GBM treatment.
Challenges and recommendations to increasing the use of exome sequencing and whole genome sequencing for diagnosing rare diseases in Brazil: an expert perspective
Authors: Félix Têmis Maria , Fischinger Moura de Souza Carolina , Oliveira João Bosco , Rico-Restrepo Mariana , Zanoteli Edmar , Zatz Mayana , Giugliani Roberto
Published: January 2023

Early diagnosis of genetic rare diseases is an unmet need in Brazil, where an estimated 10–13 million people live with these conditions. Increased use of chromosome microarray assays, exome sequencing, and whole genome sequencing as first-tier testing techniques in suitable indications can shorten the diagnostic odyssey, eliminate unnecessary tests, procedures, and treatments, and lower healthcare expenditures. A selected panel of Brazilian experts in fields related to rare diseases was provided with a series of relevant questions to address before a multi-day conference. Within this conference, each narrative was discussed and edited through numerous rounds of discussion until agreement was achieved. The widespread adoption of exome sequencing and whole genome sequencing in Brazil is limited by various factors: cost and lack of funding, reimbursement, awareness and education, specialist shortages, and policy issues. To reduce the burden of rare diseases and increase early diagnosis, the Brazilian healthcare authorities/government must address the barriers to equitable access to early diagnostic methods for these conditions. Recommendations are provided, including broadening approved testing indications, increasing awareness and education efforts, increasing specialist training opportunities, and ensuring sufficient funding for genetic testing.
Temporal variation of the temperature-mortality association in Spain: a nationwide analysis
Authors: Ordanovich Dariya , Tobías Aurelio , Ramiro Diego
Published: January 2023

Background

Although adaptation to continuously rising ambient temperatures is an emerging topic and has been widely studied at a global scale, detailed analysis of the joint indicators for long-term adaptation in Spain are scarce. This study aims to explore temporal variations of the minimum mortality temperature and mortality burden from heat and cold between 1979 and 2018.

Methods

We collected individual all-cause mortality and climate reanalysis data for 4 decades at a daily time step. To estimate the temperature-mortality association for each decade, we fitted a quasi-Poisson time-series regression model using a distributed lag non-linear model with 21 days of lag, controlling for trends and day of the week. We also calculated attributable mortality fractions by age and sex for heat and cold, defined as temperatures above and below the optimum temperature, which corresponds to the minimum mortality in each period.

Results

We analysed over 14 million deaths registered in Spain between 1979 and 2018. The optimum temperature estimated at a nationwide scale declined from 21 °C in 1979–1988 to 16 °C in 1999–2008, and raised to 18 °C in 2009–2018. The mortality burden from moderate cold showed a 3-fold reduction down to 2.4% in 2009–2018. Since 1988–1999, the mortality risk attributable to moderate (extreme) heat reduced from 0.9% (0.8%) to 0.6% (0.5%). The mortality risk due to heat in women was almost 2 times larger than in men, and did not decrease over time.

Conclusion

Despite the progressively warmer temperatures in Spain, we observed a persistent flattening of the exposure-response curves, which marked an expansion of the uncertainty range of the optimal temperatures. Adaptation has been produced to some extent in a non-uniform manner with a substantial decrease in cold-related mortality, while for heat it became more apparent in the most recent decade only.
Identifying drivers of increasing opioid overdose deaths among black individuals: a qualitative model drawing on experience of peers and community health workers
Authors: Banks Devin E. , Duello Alex , Paschke Maria E. , Grigsby Sheila R. , Winograd Rachel P.
Published: January 2023

Background

Black individuals in the USA face disproportionate increases in rates of fatal opioid overdose despite federal efforts to mitigate the opioid crisis. The aim of this study was to examine what drives increases in opioid overdose death among Black Americans based on the experience of key stakeholders.

Methods

Focus groups were conducted with stakeholders providing substance use prevention services in Black communities in St. Louis, MO (n = 14). One focus group included peer advocates and volunteers conducting outreach-based services and one included active community health workers. Focus groups were held at community partner organizations familiar to participants. Data collection was facilitated by an interview guide with open-ended prompts. Focus groups were audio recorded and professionally transcribed. Transcripts were analyzed using grounded theory to abstract line-by-line codes into higher order themes and interpret their associations.

Results

A core theme was identified from participants’ narratives suggesting that opioid overdose death among Black individuals is driven by unmet needs for safety, security, stability, and survival (The 4Ss). A lack of The 4Ss was reflective of structural disinvestment and healthcare and social service barriers perpetuated by systemic racism. Participants unmet 4S needs are associated with health and social consequences that perpetuate overdose and detrimentally impact recovery efforts. Participants identified cultural and relationship-based strategies that may address The 4Ss and mitigate overdose in Black communities.

Conclusions

Key stakeholders working in local communities to address racial inequities in opioid overdose highlighted the importance of upstream interventions that promote basic socioeconomic needs. Local outreach efforts utilizing peer services can provide culturally congruent interventions and promote harm reduction in Black communities traditionally underserved by US health and social systems.
COVID-19 vaccination does not affect male sexual functions
Authors: Mehta Poonam , Chakraborty Arijit , Andrabi Syed Waseem , Sharma Bhawani , Kumar Rakesh , Bhaskar L. V. K. S. , Rajender Singh
Published: January 2023

Background

COVID-19 infection has been linked with erectile dysfunction, which has also raised apprehensions about the impact of COVID-19 vaccination on male sexual functions. The purpose of this study was to investigate the impact of COVID-19 vaccination on male sexual functions, such as erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction.

Methods

We used International Index of Erectile Function (IIEF) questionnaire for data collection. Mixed methods were adopted for this study, which consisted of Google online form distribution and the distribution of hard copies of the form to those who were not internet friendly. All data were entered in a spreadsheet and scores were assigned to each response according to the standard scores given in the IIEF questionnaire. Fifteen questions, one corresponding to each question in the IIEF questionnaire, were included to assess the impact of COVID-19 vaccination on each sexual function.

Results

In the first part of analysis, we calculated sexual function scores and men reporting low sexual function scores (~ 15%) were excluded, providing us with 465 individuals for further analysis. Regarding the impact of COVID-19 vaccination on male sexual functions, 71% individuals reported no impact, 3% reported a decline, 2.7% reported an improvement, and 23.3% could not assess the impact. We also performed analysis on the basis of age-groups of the participants and the duration after vaccination, finding that there was no impact irrespective of the age of subjects or the length of period after vaccination.

Conclusions

COVID-19 vaccination does not affect male sexual functions, including erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall sexual satisfaction.
Features of peritoneal dendritic cells in the development of endometriosis
Authors: Qiaomei Zheng , Ping Wu , Yanjing Zhao , Jinhua Wang , Shaozhan Chen , Lihong Chen
Published: January 2023

Background

Emerging evidence of immunological dysfunction have been described in endometriosis. Dendritic cells (DCs), one of the main antigen-presenting cells, are specialized in the initiation and modulation of the adaptive immune response. Emerging studies demonstrated both endometrial and circulating differences in DCs populations in women with endometriosis. However, the role and mechanism of peritoneal DCs in endometriosis is still unclear. The present study was undertaken to explore the features of peritoneal DCs in the pathogenesis of endometriosis. This study is beneficial to further clarify the cause of endometriosis and provide a new insight into the medical treatment for endometriosis.

Methods

The study included 12 women with endometriosis and 11 women without endometriosis. The C57BL6 mouse model of endometriosis was established by intraperitoneal injection of endometrial segments. The peritoneal DCs of endometriosis patients and mouse models were analyzed by fluorescence associated cell sorting (FACS) examination.

Results

Increased cell density of peritoneal DCs were observed in endometriosis patients. Moreover, the proportion of mature DCs (mDCs, CD80highCD1alow cells) in the peritoneal DCs was lower whereas the proportion of immature DCs (iDCs, CD80lowCD1ahigh cells) was increased in endometriosis patients. Similarly, the cell density of peritoneal DCs in murine models increased immediately after the injection of endometrial tissues and reached the highest level at 14 days. In addition, the proportion of mDCs (CD11chighCD80high cells) in the peritoneal DCs decreased immediately after the injection of endometrial tissues and then increased with the time until 42 days, but still lower than the control group. In contrast, the proportion of iDCs (CD11chighCD80low cells) in the peritoneal DCs showed the opposite dynamic changes. However, after treated with LPS, the mDCs proportion was significantly increased, leading to lower volume and weight of the endometriosis lesions.

Conclusions

Increased level of peritoneal DCs facilitated the pathogenesis of endometriosis lesions, especially in the early stage of the disease. Furthermore, peritoneal DCs maturation played an important role in the development of endometriosis.
Alamandine/MrgD axis prevents TGF-β1-mediated fibroblast activation via regulation of aerobic glycolysis and mitophagy
Authors: Wang Wei , Zhang Yue , Huang Wenhui , Yuan Yafei , Hong Qiaohui , Xie Zhanzhan , Li Lijuan , Chen Yixin , Li Xu , Meng Ying
Published: January 2023

Background

Idiopathic pulmonary fibrosis is a chronic progressive, lethal disease in which ectopic lung fibroblast (LF) activation plays a vital part. We have previously shown that alamandine (ALA) exerts anti-fibrosis effects via the MAS-related G-protein coupled receptor D (MrgD). Here, we further investigate how it moderates transforming growth factor β1 (TGF-β1)-induced LF activation by regulating glucose metabolism and mitochondria autophagy (mitophagy).

Methods

In vitro, we examined glycolysis-related protein hexokinase 2 (HK2), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), and lactic acid in cells treated with TGF-β1. The oxygen consumption rate and the extracellular acidification rate were detected using Seahorse assays. Then, mitophagy was evaluated using transmission electron microscopy, mt-Keima, and the co-localization of Parkin and COX IV with LC3 and LAMP1, respectively. The autophagic degradation of HK2 and PFKFB3 was detected by 3MA and bafilomycin A1 and assessed by their co-localization with LC3 and LAMP1, respectively. The effects of ALA on LF activation markers collagen I and α-SMA were detected. The effects of ALA on glucose metabolism, mitophagy, and the activation of LF were also investigated in vivo.

Results

We found that the ALA/MrgD axis improved TGF-β1-mediated LF activation by repressing glycolysis by downregulating HK2 and PFKFB3 expression. Lactic acid sustained positive feedback between glycolysis and LF activation by maintaining the expression of HK2 and PFKFB3. We also showed that glycolysis enhancement resulted from blocking the autophagic degradation of HK2 and PFKFB3 while upregulated mRNA levels by TGF-β1, while all of those improved by ALA adding. Importantly, we determined that moderation of Parkin/LC3-mediated mitophagy by TGF-β1 also promotes glycolysis but is reversed by ALA. Furthermore, we proved that ALA counteracts the effects of bleomycin on HK2, PFKFB3, LC3, Parkin, and LF activation in vivo.

Conclusion

In this study, we show that the ALA/MrgD axis prevents TGF-β1-mediated fibroblast activation via regulation of aerobic glycolysis and mitophagy.
Blocking interleukin-23 ameliorates neuromuscular and thymic defects in myasthenia gravis
Authors: Villegas José A. , Van Wassenhove Jérôme , Merrheim Judith , Matta Karen , Hamadache Samy , Flaugère Clémence , Pothin Pauline , Truffault Frédérique , Hascoët Sébastien , Santelmo Nicola , Alifano Marco , Berrih-Aknin Sonia , le Panse Rozen , Dragin Nadine
Published: January 2023

Acetylcholine receptor (AChR) myasthenia gravis (MG) is a chronic autoimmune disease characterized by muscle weakness. The AChR+ autoantibodies are produced by B-cells located in thymic ectopic germinal centers (eGC). No therapeutic approach is curative. The inflammatory IL-23/Th17 pathway is activated in the thymus as well as in the blood and the muscle, contributing to the MG pathogenic events. We aimed to study a potential new therapeutic approach that targets IL-23p19 (IL-23) in the two complementary preclinical MG models: the classical experimental MG mouse model (EAMG) based on active immunization and the humanized mouse model featuring human MG thymuses engrafted in NSG mice (NSG-MG). In both preclinical models, the anti-IL-23 treatment ameliorated MG clinical symptoms. In the EAMG, the treatment reduced IL-17 related inflammation, anti-AChR IgG2b antibody production, activated transduction pathway involved in muscle regeneration and ameliorated the signal transduction at the neuromuscular junction. In the NSG-MG model, the treatment reduced pathogenic Th17 cell population and expression of genes involved in eGC stabilization and B-cell development in human MG thymus biopsies. Altogether, these data suggest that a therapy targeting IL-23p19 may promote significant clinical ameliorations in AChR+ MG disease due to concomitant beneficial effects on the thymus and skeletal muscle defects.
HIV infection of non-classical cells in the brain
Authors: Wahl Angela , Al-Harthi Lena
Published: January 2023

HIV-associated neurological disorders (HAND) affect up to 50% of people living with HIV (PLWH), even in the era of combination antiretroviral therapy (cART). HIV-DNA can be detected in the cerebral spinal fluid (CSF) of approximately half of aviremic ART-suppressed PLWH and its presence is associated with poorer neurocognitive performance. HIV DNA + and HIV RNA + cells have also been observed in postmortem brain tissue of individuals with sustained cART suppression. In this review, we provide an overview of how HIV invades the brain and HIV infection of resident brain glial cells (astrocytes and microglia). We also discuss the role of resident glial cells in persistent neuroinflammation and HAND in PLWH and their potential contribution to the HIV reservoir. HIV eradication strategies that target persistently infected glia cells will likely be needed to achieve HIV cure.
Radiation-induced senescence: therapeutic opportunities
Authors: Kim Jae Ho , Brown Stephen L. , Gordon Marcia N.
Published: January 2023

The limitation of cancer radiotherapy does not derive from an inability to ablate tumor, but rather to do so without excessively damaging critical tissues and organs and adversely affecting patient’s quality of life. Although cellular senescence is a normal consequence of aging, there is increasing evidence showing that the radiation-induced senescence in both tumor and adjacent normal tissues contributes to tumor recurrence, metastasis, and resistance to therapy, while chronic senescent cells in the normal tissue and organ are a source of many late damaging effects. In this review, we discuss how to identify cellular senescence using various bio-markers and the role of the so-called senescence-associated secretory phenotype characteristics on the pathogenesis of the radiation-induced late effects. We also discuss therapeutic options to eliminate cellular senescence using either senolytics and/or senostatics. Finally, a discussion of cellular reprogramming is presented, another promising avenue to improve the therapeutic gain of radiotherapy.
The relationship between quality of life and health promotion behavior in patients with type B aortic dissection: a cross-sectional study
Authors: Tu Jianxin , Wang Fei , Yin Furong , Zhang Linxue , Zhao Benli , Zhou Jiamei
Published: January 2023

Background

To understand the current situation of health promotion behavior and quality of life among aortic dissection survivors and the correlation between them.

Methods

Sociodemographic characteristics were collected. T-test and variance analysis were applied for univariate analysis. Quality of life was measured using the SF-36 Questionnaire, and health-promoting behaviors were measured using the aortic dissection health promotion behavior questionnaire. The association between type B aortic dissection survivors’ health promotion behavior and health status questionnaire (SF-36) scores was determined through Pearson’s correlation coefficients. This association was analyzed through multivariable regression analysis.

Results

A total of 131 type B aortic dissection survivors were evaluated through the self-developed aortic dissection patient health promotion behavior scale and health status questionnaire (SF-36). Results showed that the health promotion behavior of Stanford B aortic dissection survivors (85.05 ± 11.28) correlated with their Mental Component Summary (MCS) (55.23 ± 30.72; r = 0.359, P < 0.01). The model showed 39.00% variance shared between behavior motivation and MCS (R2 = 0.390, F = 13.189, P < 0.01).

Conclusion

Type B aortic dissection survivors in Zunyi, China had a lower quality of life. Medical staff can formulate intervention measures from behavioral motivation to improve the quality of life of aortic dissection survivors.
Aldosterone inhibits Dot1l expression in guinea pig cochlea
Authors: Zhong Shixun , Zhang Biyun , Qin Li , Wang Qianying , Luo Xiaoli
Published: January 2023

Background

Aldosterone relieves transcriptional repression of epithelial sodium channel (ENaC) by inhibiting Dot1a and Af9 expression and their interaction with ENaC promoter in various tissues. Expressions of ENaC and Af9 in inner ear have been identified. However, it is not known how Dot1l is regulated by aldosterone in inner ear.

Methods

Twenty-eight adult guinea pigs were randomly divided into the control group and treatment group. Aldosterone 1 mg/kg/d was injected intraperitoneally in the treatment group and saline in the control group for 7 days. Animals were killed 1 month later following auditory brainstem response examination. Histomorphology of cochlea was detected with hematoxylin–eosin staining, and Dot1l expression was examined with immunohistochemistry and Western blot.

Results

There was no significant difference in ABR thresholds before and after injection of aldosterone or saline in either group. Endolymphatic hydrops was found in 75% of animals in the treatment group. Dot1l was found in both groups in the stria vascularis, Reissner’s membrane, spiral limbus, organ of Corti and spiral ligament. Dot1l expression in the treatment group was decreased by aldosterone.

Conclusions

Dot1l in guinea pig cochlea is inhibited by aldosterone with induction of endolymphatic hydrops. Dot1l may be closely related to endolymph regulation by aldosterone and to pathogenesis of Meniere’s disease.
Reversible flowering of CuO nanoclusters via conversion reaction for dual-ion Li metal batteries
Authors: Li Siying , Lee Jung-Hun , Hwang Soo Min , Kim Young-Jun
Published: January 2023

Dual-ion Li metal batteries based on non-flammable SO2-in-salt inorganic electrolytes ( Li–SO2 batteries) offer high safety and energy density. The use of cupric oxide (CuO) as a self-activating cathode material achieves a high specific capacity with cost-effective manufacturing in Li–SO2 batteries, but its cycle retention performance deteriorates owing to the significant morphological changes of the cathode active materials. Herein, we report the catalytic effect of carbonaceous materials used in the cathode material of Li–SO2 batteries, which act as templates to help recrystallize the active materials in the activation and conversion reactions. We found that the combination of oxidative-cyclized polyacrylonitrile (PAN) with N-doped carbonaceous materials and multi-yolk-shell CuO (MYS-CuO) nanoclusters as cathode active materials can significantly increase the specific capacity to 315.9 mAh g− 1 (93.8% of the theoretical value) at 0.2 C, which corresponds to an energy density of 1295 Wh kgCuO−1, with a capacity retention of 84.46% at the 200th cycle, and the cathode exhibited an atypical blossom-like morphological change.
Stable overexpression and targeted gene deletion of the causative agent of ash dieback Hymenoscyphus fraxineus
Authors: Lutz Tobias , Hadeler Birgit , Jaeckel Mareike , Schulz Barbara , Heinze Cornelia
Published: January 2023

Background

Due to the infection with the invasive ascomycete Hymenoscyphus fraxineus, which has been replacing the closely related and non-pathogenic native Hymenoscyphus albidus, the European ashes, Fraxinus excelsior (also known as the common ash), Fraxinus angustifolia (also known as narrow-leaved ash) and Fraxinus ornus (also known as the manna ash) are at risk. Hymenoscyphus fraxineus is the causative agent of ash dieback of the European ashes, but is non-pathogenic to the native Asian ash Fraxinus mandshurica (also known as the Manchurian ash). Even though the invasion of H. fraxineus is a great threat for ashes in Europe, the fungal biology is still poorly understood. By the use of live cell imaging and targeted gene knock-out, the fungal life cycle and host–pathogen interaction can be studied in more detail.

Results

Here, we developed a protocol for the preparation of protoplasts from mycelium of H. fraxineus, for their regeneration and for stable transformation with reporter genes and targeted gene knock-out by homologous recombination. We obtained mutants with various levels of reporter gene expression which did not correlate with the number of integrations. In an in vitro infection assay, we demonstrated the suitability of reporter gene overexpression for fungal detection in plant tissue after inoculation. As a proof of principle for targeted gene knock-out, the hygromycin resistance cassette of a reporter gene-expressing mutant was replaced with a geneticin resistance cassette.

Conclusions

The invasive fungal pathogen H. fraxineus is threatening the European ashes. To develop strategies for pest management, a better understanding of the fungal life cycle and its host interaction is crucial. Here, we provide a protocol for stable transformation of H. fraxineus to obtain fluorescence reporter strains and targeted gene knock-out mutants. This protocol will help future investigations on the biology of this pathogen.
Digital technologies, technological improvement rates, and innovations “Made in Switzerland”
Authors: Niggli Matthias , Rutzer Christian
Published: January 2023

Technologies evolve at different paces and their rate of improvement varies considerably. We demonstrate that the fastest technological progress currently occurs in the digital domain and empirically investigate the relationship between technologies’ improvement rates and breakthrough innovations as measured by forward citations of patents. Our empirical estimates suggest that patents from the digital sphere, as well as those related to fast-improving technologies, are associated with a higher probability to produce breakthrough innovations. We then investigate Swiss core industries’ specialization patterns toward these potential high-impact technologies and compare the state of cutting-edge innovation in Switzerland to other countries. Our findings imply that the Swiss innovation system is among the laggards regarding innovations in today’s fastest improving digital technologies.
Taste adaptations associated with host specialization in the specialistDrosophila sechellia
Authors: Reisenman Carolina E. , Wong Joshua , Vedagarbha Namrata , Livelo Catherine , Scott Kristin
Published: January 2023

Chemosensory-driven host plant specialization is a major force mediating insect ecological adaptation and speciation. Drosophila sechellia, a species endemic to the Seychelles islands, feeds and oviposits on Morinda citrifolia almost exclusively. This fruit is harmless to D. sechellia but toxic to other Drosophilidae, including the closely related generalists D. simulans and D. melanogaster, because of its high content of fatty acids. While several olfactory adaptations mediating D. sechellia’s preference for its host have been uncovered, the role of taste has been much less examined. We found that D. sechellia has reduced taste and feeding aversion to bitter compounds and host fatty acids that are aversive to D. melanogaster and D. simulans. The loss of aversion to canavanine, coumarin and fatty acids arose in the D. sechellia lineage, as its sister species D. simulans showed responses akin to those of D. melanogaster. Drosophila sechellia has increased taste and feeding responses towards M. citrifolia. These results are in line with D. sechellia’s loss of genes that encode bitter gustatory receptors (GRs) in D. melanogaster. We found that two GR genes which are lost in D. sechellia, GR39a.a and GR28b.a, influence the reduction of aversive responses to some bitter compounds. Also, D. sechellia has increased appetite for a prominent host fatty acid compound that is toxic to its relatives. Our results support the hypothesis that changes in the taste system, specifically a reduction of sensitivity to bitter compounds that deter generalist ancestors, contribute to the specialization of D. sechellia for its host.
Τροποποιητές Τ-πρωτεϊνοπαθητικών μηχανισμών
Authors: Βούρκου Εργίνα
Published: January 2023

Οι νευροεκφυλιστικές ασθένειες περιλαμβάνουν ένα σύνολο ασθενειών που σχετίζονται με τη προοδευτική απώλεια της δομής ή της λειτουργίας των νευρώνων (εκφύλιση) και οδηγούν στο θάνατο των νευρώνων και των ιστών και συνεπώς στην επικείμενη δυσλειτουργία του εγκεφάλου. Μια ιδιαίτερη κατηγορία των νευροεκφυλιστικών ασθενειών αποτελούν οι Τ-πρωτεϊνοπάθειες, δηλαδή οι ασθένειες που σχετίζονται με την πρωτεΐνη Τ (με κυριότερη τη νόσο του Alzheimer) και χαρακτηρίζονται από υπερ-φωσφορυλιωμένη πρωτεΐνη T ή από μεταλλάξεις στο γονίδιο τ. Τα τελευταία χρόνια έχει διεξαχθεί πληθώρα μελετών για την ανάδειξη των μοριακών μηχανισμών με τους οποίους η πρωτεΐνη Τ οδηγεί σε νευροεκφυλισμό. Στόχος της παρούσας εργασίας ήταν ο χαρακτηρισμός συγκεκριμένων θέσεων φωσφορυλίωσης της πρωτεΐνης Τ που καθορίζουν την τοξικότητά της καθώς και η μελέτη του ρόλου που διαδραματίζουν τα συσσωματώματα στις διεργασίες που απαιτούνται για την εξαρτώμενη από την πρωτεϊνοσύνθεση μνήμη. Η κατανόηση του προτύπου και του τρόπου ρύθμισης της φωσφορυλίωσης της ανθρώπινης πρωτεΐνης Τ είναι σημαντική για την παρακολούθηση και εξέλιξη διαφόρων Τ-πρωτεϊνοπαθειών. Η αναγνώριση συγκεκριμένων θέσεων φωσφορυλίωσης, οι οποίες δρουν ως «θυροφύλακες» για μια σειρά άλλων επικείμενων φωσφορυλιώσεων, μπορεί να αποτελέσει ένα χρήσιμο βιοδείκτη για την πρόγνωση των Τ-πρωτεϊνοπαθειών. Ενώ, η διερεύνηση του ρόλου των συσσωματωμάτων σε συγκεκριμένες γνωστικές λειτουργίες μπορεί να υποδείξει πιθανούς φαρμακευτικούς στόχους (π.χ φάρμακα που επάγουν ή αναστέλλουν τη συσσωμάτωση), ως καταλληλότερους για την θεραπεία των γνωστικών δυσλειτουργιών και στον άνθρωπο.
Ενδο-επαγγελματικές μεταβολές στην κοινωνική στρωμάτωση σε περιόδους κρίσης
Authors: Κούρας Γεώργιος
Published: January 2023

Η διατριβή εξετάζει τα μοτίβα και τις διαδικασίες ενδο-επαγγελματικής κοινωνικής στρωμάτωσης μεταξύ Ελλήνων και Αλβανών οικοδόμων και πως οι διαχωρισμοί και οι εργασιακές συνήθειες μεταβάλλονται σε περιόδους κρίσης. Πρόκειται για μια μελέτη περίπτωσης των εργαζόμενων στον κατασκευαστικό κλάδο στην Αθήνα από το 2020-2022, με βάση την επιτόπια έρευνα. Στην Ελλάδα, η εργασία των μεταναστών στον κατασκευαστικό κλάδο είναι ένα σταθερό χαρακτηριστικό και η απασχόληση στο επάγγελμα του οικοδόμου ήταν παραδοσιακά συνδεδεμένη με περιθωριακές ομάδες. Το ερώτημα ωστόσο είναι, ποιες είναι οι νέες γραμμές οριοθέτησης που αντικαθιστούν τις παλιές, ποιες διαδικασίες διαιωνίζουν τον εγκλωβισμό των εργατών και πως οι διαδικασίες από-ειδίκευσης τους επηρεάζουν. Κατά τη διάρκεια της κρίσης, τα υψηλά επίπεδα ανεργίας, σε συνδυασμό με τη μείωση των μισθών και της απασχόλησης, οδήγησαν σε αυξημένο ανταγωνισμό μεταξύ Ελλήνων και μεταναστών στον κατασκευαστικό κλάδο. Ο κοινωνικός αντίκτυπος των παραπάνω, είναι η θέσπιση νέων κριτηρίων στον καταμερισμό της εργασίας και ένα νέο σύνολο σχέσεων που δημιουργούνται στον ίδιο τύπο εργασίας. Έτσι, η συγκεκριμένη διατριβή πρόκειται να εξετάσει ποιες είναι οι νέες τακτικές που υιοθετούν οι εργαζόμενοι για να παραμείνουν ενεργοί στο επάγγελμα.Σε πολλές χώρες σε όλη την Ευρώπη, οι κανονισμοί για την απασχόληση, τη μετανάστευση και τις δεξιότητες, έχουν υποστεί μετασχηματισμούς που αναδιαμορφώνουν τη σύνθεση του μεταναστευτικού εργατικού δυναμικού στις αγορές εργασίας της οικοδομής. Επίσης, ο κατασκευαστικός κλάδος παρουσιάζει αύξηση των μορφών αυτό-απασχόλησης και μεταφερόμενου εργατικού δυναμικού, όπου και τα δυο εξυπηρετούν τη μείωση των μισθών, των παροχών και άλλων μορφών κοινωνικής ασφάλισης. Ως αποτέλεσμα, τα μοτίβα της απορρύθμισης της απασχόλησης, έχουν κενά στην οικοδόμηση της ασφάλειας των εργαζομένων, μέσω της αύξησης των μορφών ψευδο-απασχόλησης και των υψηλών ποσοστών υπεργολαβίας. Χρησιμοποιώντας αρχεία, ιστορικά δεδομένα και συλλέγοντας μαρτυρίες από τις αρχές της δεκαετίας του ’90 για Αλβανούς μετανάστες, η διατριβή στοχεύει να διαφωτίσει τις βασικές παραμέτρους που εμπλέκονται στη στρωμάτωση μεταναστών και γηγενών εργατών.