bluuebunny/crossref_metadata_2025 huggingface dataset:
The Assessment of Long-Term Care Environments for Wayfinding Design
Authors: Davis Rebecca , Calkins Margaret , Cai Hui
Published: June 2023

Objectives:

The purpose of this article is to compare three different methods to assess the complexity of a long-term care (LTC) environment for wayfinding before and after an environmental design intervention. The methods include space syntax (SS), the Wayfinding Checklist (WC), and the Tool to Assess Wayfinding Complexity (TAWC).

Background:

Wayfinding is important to maintain older adults’ independent functioning. The design of environments can impact wayfinding ability by providing support; this can be via building structure or by environmental design features such as signage and landmarks. Few methods or tools have been scientifically validated to assess environments for wayfinding complexity. In order to compare environments in terms of complexity and to measure the impact of interventions, valid and reliable tools are necessary.

Methods:

This article discusses the results of the use of three wayfinding design assessment tools using three routes in one LTC environment. The results of the three tools are discussed.

Results:

SS analysis could quantitatively measure the complexity of routes using integration values, which indicates connectedness. The TAWC and the WC were able to measure differences in visual field scores pre- and postenvironmental intervention. There were limitations to each tool: the lack of psychometric properties for the TAWC and the WC, and the lack of ability to measure changes in design features within visual fields with SS.

Conclusions:

Multiple tools to assess environments for wayfinding design may be needed in studies that test environmental interventions. Future research is needed to provide psychometric testing for the tools.
Novel Posterior Shoulder Stretching With Rapid Eccentric Contraction and Static Stretching in Patients With Subacromial Pain Syndrome: A Randomized Trial
Authors: Türksan Halime Ezgi , Yeşilyaprak Sevgi Sevi , Erduran Mehmet , Özcan Cem
Published: June 2023

Background:

In subacromial pain syndrome (SPS), it is unknown whether posterior shoulder stretching exercises (PSSE) with rapid eccentric contraction, a muscle energy technique, improve clinical and ultrasonographic outcomes more than no stretching or static PSSE.

Hypothesis:

PSSE with rapid eccentric contraction is superior to no stretching and static PSSE in improving clinical and ultrasonographic outcomes in SPS.

Study Design:

Randomized controlled trial.

Level of Evidence:

Level 1.

Methods:

Seventy patients with SPS and glenohumeral internal rotation deficit were randomized into the modified cross-body stretching with rapid eccentric contraction group (EMCBS; n = 24), static MCBS group (SMCBS; n = 23), or control group (CG; n = 23). In addition to 4-week physical therapy, EMCBS received PSSE with rapid eccentric contraction, SMCBS static PSSE, and CG no PSSE. The primary outcome was internal rotation range of motion (ROM). Secondary outcomes were posterior shoulder tightness, external rotation ROM (ERROM), pain, modified Constant-Murley score, short form of the disabilities of the arm, shoulder, and hand questionnaire (QuickDASH), rotator cuff strength, acromiohumeral distance (AHD), supraspinatus tendon thickness, and supraspinatus tendon occupation ratio (STOR).

Results:

Shoulder mobility, pain, function and disability, strength, AHD, and STOR improved in all groups ( P < 0.05).

Conclusion:

In patients with SPS, PSSE with rapid eccentric contraction and static PSSE were superior to no stretching in improving clinical and ultrasonographic outcomes. Stretching with rapid eccentric contraction was not superior to static stretching, but improved ERROM compared with no stretching.

Clinical Relevance:

In SPS, both PSSE with rapid eccentric contraction and static PSSE included in physical therapy program are beneficial to improve posterior shoulder mobility and other clinical and ultrasonographic outcomes. In the case of ERROM deficiency, rapid eccentric contraction might be preferred.
Associations Between Parental Psychological Control and COVID-19 Pandemic-Related Negative Emotions: The Role of Resilience and Emotion Regulation
Authors: Ma Xiaole , Wang Xingchao , Gao Zhao
Published: June 2023

Studies focusing on risk factors for negative emotions related to the COVID-19 pandemic remain limited. We examined the underlying mechanism of resilience and emotion regulation on the association between parental psychological control and COVID-19 pandemic-related negative emotions. A total of 400 Chinese college students (207 males; Mage = 19.78 ± 1.72 years) completed a cross-sectional survey including Parental Psychological Control Scale, Profile of Mood States Scale, Brief Resilience Scale, and Emotion Regulation Questionnaire during the pandemic. Using PROCESS macro, results indicated that resilience partially mediated the association between parental psychological control and COVID-19 pandemic-related negative emotions. Expressive suppression, but not cognitive reappraisal, moderated the mediating path. Specifically, parental psychological control was a stronger predictor of resilience among those who rarely used expressive suppression. Correcting maladaptive parenting would be beneficial for college students' mental health during COVID-19 as well as for the improvement of coping capacity and adaptation outcomes to stress.
Hot topics and fresh look on old problems: A new vision of the Journal of Endometriosis and Pelvic Pain Disorders
Authors: Ciebiera Michał , Abramiuk Monika , Bartnik Paweł , Feduniw Stepan , Kacperczyk-Bartnik Joanna , Włodarczyk Marta , Żeber-Lubecka Natalia
Published: June 2023

We would like to announce a new vision of the Journal of Endometriosis and Pelvic Pain Disorders. Thanks to the contribution by former Editors-in-Chief, Associate Editors, and Editorial Board members, as well as all Readers we have a stable base and our journal is still growing. Today, it is safe to say that the journal has already matured and that it has a specific goal, specific groups of authors and readers—each of them is unique. The audience of our magazine mostly includes clinicians and scientists dealing with the subject of broadly understood gynecology with an emphasis on minimally-invasive gynecology, as well as the issues of pathophysiology, particularly comprising the topic of endometriosis, pelvic pain, reproduction, uterine fibroids, or some parts of endocrinology or gynecological oncology. Currently, our journal publishes a high quality peer-reviewed basic and clinical original research articles and critical reviews focusing specifically on the diagnosis, medical, and surgical treatment of endometriosis, adenomyosis, and associated disorders in all their multidimensional aspects. In our strategy for the forthcoming years, we will especially keep place for the most important current problems, controversial or unresolved topics in particular, which are not lacking in case of such a poorly understood pathology as endometriosis, pelvic pain, or uterine fibroids. To sum up, we believe that our journal will surely continue developing in all most important areas of clinical and scientific publishing—these mean standards, basic research, translational medicine, and clinical concept.
Poverty, Policy and the Poor
Authors: Pawar Manohar
Published: June 2023

This article and editorial aims to point out 193 governments’ unrealised pledge to eradicate extreme poverty and end hunger by 2030. The latest progress report shows that overall progress against the sustainable development goals 1 and 2 is not on track. It calls for renewed commitment by governments to allocate adequate resources and take practical steps to end poverty and hunger by engaging people at local levels at a global scale. It also introduces the special issue to critically analyse connections and disconnections among poverty, policy and the poor with a hope to engender further thought, research and action to end poverty and hunger.
Genome-wide identification of the PYL gene family of tea plants (Camellia sinensis) revealed its expression profiles under different stress and tissues
Authors: An Yanlin , Mi Xiaozeng , Xia Xiaobo , Qiao Dahe , Yu Shirui , Zheng Huayan , Jing Tingting , Zhang Feng
Published: June 2023

Background

PYL (Pyrabactin resistance 1-like) protein is a receptor of abscisic acid (ABA), which plays an important role in ABA signaling and influences plant growth and development and stress response. However, studies on PYL gene family in tea plants have not been reported.

Results

In this study, we identified 20 PYL genes from the reference genome of tea plant (‘Shuchazao’). Phylogeny analysis indicated that PYLs from tea and other plant species were clustered into seven groups. The promoter region of PYL genes contains a large number of cis-elements related to hormones and stresses. A large number of PYL genes responding to stress were found by analyzing the expression levels of abiotic stress and biotic stress transcriptome data. For example, CSS0047272.1 were up-regulated by drought stress, and CSS0027597.1 could respond to both anthracnose disease and geometrid feeding treatments. In addition, 10 PYL genes related to growth and development were verified by RT-qPCR and their tissue expression characteristics were revealed.

Conclusions

Our results provided a comprehensive characteristic of the PYL gene family in tea plants and provided an important clue for further exploring its functions in the growth and development, and resistance to stress of tea plants.
Can the current monkeypox affect the heart? A systematic review of case series and case report
Authors: Sayad Reem , Siddiq Abdelmonem , Hashim Ahmed , Elsaeidy Ahmed Saad
Published: June 2023

Background

Monkeypox is a zoonotic viral infection first reported in May 2022. Monkeypox cases present with prodromal symptoms, rash, and/or systemic complications. This study systematically reviews the monkeypox cases presented with any cardiac complications.

Methods

A systematic literature search was done to locate papers that discuss any cardiac complications associated with monkeypox; then, data were analyzed qualitatively.

Results

Nine articles, including the 13 cases that reported cardiac complications of the disease, were included in the review. Five cases previously had sex with men, and two cases had unprotected intercourse, which reveals the importance of the sexual route in disease transmission. All cases have a wide spectrum of cardiac complications, such as acute myocarditis, pericarditis, pericardial effusion, and myopericarditis.

Conclusion

This study clarifies the potential for cardiac complications in monkeypox cases and provides avenues for future research to determine the underlying mechanism. Also, we found that the cases with pericarditis were treated with colchicine, and those with myocarditis were treated with supportive care or cardioprotective treatment (Bisoprolol and Ramipril). Furthermore, Tecovirimat is used as an antiviral drug for 14 days.
Prediction of rehospitalization and mortality risks for skilled nursing facilities using a dimension reduction approach
Authors: David Gomez Juan Camilo , Cochran Amy , Smith Maureen , Zayas-Cabán Gabriel
Published: June 2023

Background

Hospitals are incentivized to reduce rehospitalization rates, creating an emphasis on skilled nursing facilities (SNFs) for post-hospital discharge. How rehospitalization rates vary depending on patient and SNF characteristics is not well understood, in part because these characteristics are high-dimensional. We sought to estimate rehospitalization and mortality risks by patient and skilled nursing facility (SNF) leveraging high-dimensional characteristics.

Methods

Using 1,060,337 discharges from 13,708 SNFs of Medicare patients residing or visiting a provider in Wisconsin, Iowa, and Illinois, factor analysis was performed to reduce the number of patient and SNF characteristics. K-means clustering was applied to SNF factors to categorize SNFs into groups. Rehospitalization and mortality risks within 60 days of discharge was estimated by SNF group for various values of patient factors.

Results

Patient and SNF characteristics (616 in total) were reduced to 12 patient factors and 4 SNF groups. Patient factors reflected broad conditions. SNF groups differed in beds and staff capacity, off-site services, and physical and occupational therapy capacity; and in mortality and rehospitalization rates for some patients. Patients with cardiac, orthopedic, and neuropsychiatric conditions are associated with better outcomes when assigned to SNFs with greater on-site capacity (i.e. beds, staff, physical and occupational therapy), whereas patients with conditions related to cancer or chronic renal failure are associated with better outcomes when assigned to SNFs with less on-site capacity.

Conclusions

Risks of rehospitalization and mortality appear to vary significantly by patient and SNF, with certain SNFs being better suited for some patient conditions over others.
Family caregiver’s concerns and anxiety about unaccompanied out-of-home activities of persons with cognitive impairment
Authors: Tsuda Shuji , Matsumoto Hiroshige , Takehara Shun , Yabuki Tomoyuki , Hotta Satoko
Published: June 2023

Background

Although people with cognitive impairment highly value social participation in out-of-home activities, their families typically perceive concerns and experience anxiety over such activities. This study aimed to elucidate the underlying concerns and factors associated with family caregivers’ anxiety over the individual’s unaccompanied out-of-home activities.

Methods

In December 2021, we conducted a cross-sectional e-survey of family caregivers of individuals with early-stage cognitive impairment. Caregivers’ concerns about ten common risks related to out-of-home activities were cross-tabulated by specific anxiety levels to examine trend associations. With the variables of caregivers and their individuals across the five domains, we ran logistic regression analyses to determine explanatory models for anxiety.

Results

The study participants were 1,322 family caregivers of people whose cognitive function varied from intact to possible mild dementia according to the Dementia Assessment Sheet for Community-based Integrated Care System 8-item. Significant associations were found between the prevalence of concerns and the degree of anxiety, even without actual experience with the issues of concern. Among the five domains, individual dementia characteristics and social behaviors were the predominant factors attributed to caregiver anxiety. Caregivers’ no anxiety state was significantly associated with: younger age (OR 4.43, 95% CI 1.81–10.81), no detectable cognitive decline (OR 3.34, 95% CI 1.97–5.64), free from long-term care (LTC) (OR 3.52, 95% CI 1.72–7.21), no manifestation of behavioral and psychological symptoms of dementia (BPSD) (OR 13.22, 95% CI 3.06–57.01), and not engaging in unaccompanied out-of-home activities (OR 3.15, 95% CI 1.87–5.31). Their severe anxiety was positively associated with being on LTC (OR 3.39, 95% CI 2.43–4.72) and minor BPSD (OR 1.43, 95% CI 1.05–1.95), and negatively associated with engagement in unaccompanied out-of-home activities (OR 0.31, 95% CI 0.23–0.43).

Conclusions

The study found that family caregivers’ anxiety was associated with concerns about behavioral issues, regardless of actual experiences. There were two significant associations in opposite directions between caregivers’ anxiety and the individual’s engagement in out-of-home activities. In the early phase of cognitive impairment, caregivers may intuitively interpret the individual’s behavior and feel anxious. Educational support may provide reassurance and enable caregivers to facilitate out-of-home activities.
Does coping with pain help the elderly with cardiovascular disease? The association of sense of coherence, spiritual well-being and self-compassion with quality of life through the mediating role of pain self-efficacy
Authors: Salehi Nahid , Afrashteh Majid Yousefi , Majzoobi Mohammad Reza , Ziapour Arash , Janjani Parisa , Karami Sahar
Published: June 2023

Background

Population ageing is considered one of the biggest challenges facing the world, and the status of the elderly in society and their quality of life (QOL) have proved to be a concern in professional and scientific research circles. As a result, the current study sought to investigate the role of pain self-efficacy (PSE) as a moderator in the relationship between sense of coherence (SOC), spiritual well-being, and self-compassion with QOL in Iranian elderly with cardiovascular disease (CVD).

Method

This was a correlational study of the path analysis type. The statistical population included all elderly people with CVD who were at least 60 years of age in Kermanshah Province, Iran, in 2022, of whom 298 (181 men and 117 women) were selected using convenience sampling and according to the inclusion and exclusion criteria. The participants answered questionnaires from the World Health Organization on QOL, Paloutzian and Ellison’s spiritual well-being, Nicholas’s PSE, Antonovsky’s SOC, and Raes et al.’s self-compassion.

Results

The results of path analysis demonstrated that the hypothesized model of this study has a good fit in the studied sample. There were significant paths between SOC (β = 0.39), spiritual well-being (β = 0.13) and self-compassion (β = 0.44) with PSE. Although there were significant paths between SOC (β = 0.16) and self-compassion (β = 0.31) with QOL, there was no significant path between spiritual well-being and QOL (β = 0.06). Besides, there was a significant path between PSE and QOL (β = 0.35). Finally, PSE was found to mediate the relationship of SOC, spiritual well-being and self-compassion with QOL.

Conclusion

The results may provide psychotherapists and counselors working in this field of inquiry with advantageous information to choose or create a useful therapeutic method to work with the elderly with CVD. Meanwhile, other researchers are suggested to examine other variables which may serve a mediating role in the mentioned model.
Social vulnerability indices: a scoping review
Authors: Mah Jasmine Cassy , Penwarden Jodie Lynn , Pott Henrique , Theou Olga , Andrew Melissa Kathryn
Published: June 2023

Background

Social vulnerability occurs when the disadvantage conveyed by poor social conditions determines the degree to which one’s life and livelihood are at risk from a particular and identifiable event in health, nature, or society. A common way to estimate social vulnerability is through an index aggregating social factors. This scoping review broadly aimed to map the literature on social vulnerability indices. Our main objectives were to characterize social vulnerability indices, understand the composition of social vulnerability indices, and describe how these indices are utilized in the literature.

Methods

A scoping review was conducted in six electronic databases to identify original research, published in English, French, Dutch, Spanish or Portuguese, and which addressed the development or use of a social vulnerability index (SVI). Titles, abstracts, and full texts were screened and assessed for eligibility. Data were extracted on the indices and simple descriptive statistics and counts were used to produce a narrative summary.

Results

In total, 292 studies were included, of which 126 studies came from environmental, climate change or disaster planning fields of study and 156 studies were from the fields of health or medicine. The mean number of items per index was 19 (SD 10.5) and the most common source of data was from censuses. There were 122 distinct items in the composition of these indices, categorized into 29 domains. The top three domains included in the SVIs were: at risk populations (e.g., % older adults, children or dependents), education, and socioeconomic status. SVIs were used to predict outcomes in 47.9% of studies, and rate of Covid-19 infection or mortality was the most common outcome measured.

Conclusions

We provide an overview of SVIs in the literature up to December 2021, providing a novel summary of commonly used variables for social vulnerability indices. We also demonstrate that SVIs are commonly used in several fields of research, especially since 2010. Whether in the field of disaster planning, environmental science or health sciences, the SVIs are composed of similar items and domains. SVIs can be used to predict diverse outcomes, with implications for future use as tools in interdisciplinary collaborations.
A potential cost of evolving epibatidine resistance in poison frogs
Authors: York Julia M. , Borghese Cecilia M. , George Andrew A. , Cannatella David C. , Zakon Harold H.
Published: June 2023

Background

Some dendrobatid poison frogs sequester the toxin epibatidine as a defense against predators. We previously identified an amino acid substitution (S108C) at a highly conserved site in a nicotinic acetylcholine receptor β2 subunit of dendrobatid frogs that decreases sensitivity to epibatidine in the brain-expressing α4β2 receptor. Introduction of S108C to the orthologous high-sensitivity human receptor similarly decreased sensitivity to epibatidine but also decreased sensitivity to acetylcholine, a potential cost if this were to occur in dendrobatids. This decrease in the acetylcholine sensitivity manifested as a biphasic acetylcholine concentration–response curve consistent with the addition of low-sensitivity receptors. Surprisingly, the addition of the β2 S108C into the α4β2 receptor of the dendrobatid Epipedobates anthonyi did not change acetylcholine sensitivity, appearing cost-free. We proposed that toxin-bearing dendrobatids may have additional amino acid substitutions protecting their receptors from alterations in acetylcholine sensitivity. To test this, in the current study, we compared the dendrobatid receptor to its homologs from two non-dendrobatid frogs.

Results

The introduction of S108C into the α4β2 receptors of two non-dendrobatid frogs also does not affect acetylcholine sensitivity suggesting no additional dendrobatid-specific substitutions. However, S108C decreased the magnitude of neurotransmitter-induced currents in Epipedobates and the non-dendrobatid frogs. We confirmed that decreased current resulted from fewer receptors in the plasma membrane in Epipedobates using radiolabeled antibodies against the receptors. To test whether S108C alteration of acetylcholine sensitivity in the human receptor was due to (1) adding low-sensitivity binding sites by changing stoichiometry or (2) converting existing high- to low-sensitivity binding sites with no stoichiometric alteration, we made concatenated α4β2 receptors in stoichiometry with only high-sensitivity sites. S108C substitutions decreased maximal current and number of immunolabeled receptors but no longer altered acetylcholine sensitivity.

Conclusions

The most parsimonious explanation of our current and previous work is that the S108C substitution renders the β2 subunit less efficient in assembling/trafficking, thereby decreasing the number of receptors in the plasma membrane. Thus, while β2 S108C protects dendrobatids against sequestered epibatidine, it incurs a potential physiological cost of disrupted α4β2 receptor function.
Targeting cGAS/STING signaling-mediated myeloid immune cell dysfunction in TIME
Authors: Kumar Vijay , Bauer Caitlin , Stewart John H.
Published: June 2023

Myeloid immune cells (MICs) are potent innate immune cells serving as first responders to invading pathogens and internal changes to cellular homeostasis. Cancer is a stage of altered cellular homeostasis that can originate in response to different pathogens, chemical carcinogens, and internal genetic/epigenetic changes. MICs express several pattern recognition receptors (PRRs) on their membranes, cytosol, and organelles, recognizing systemic, tissue, and organ-specific altered homeostasis. cGAS/STING signaling is a cytosolic PRR system for identifying cytosolic double-stranded DNA (dsDNA) in a sequence-independent but size-dependent manner. The longer the cytosolic dsDNA size, the stronger the cGAS/STING signaling activation with increased type 1 interferon (IFN) and NF-κB-dependent cytokines and chemokines’ generation. The present article discusses tumor-supportive changes occurring in the tumor microenvironment (TME) or tumor immune microenvironment (TIME) MICs, specifically emphasizing cGAS/STING signaling-dependent alteration. The article further discusses utilizing MIC-specific cGAS/STING signaling modulation as critical tumor immunotherapy to alter TIME.
Incremental effect of coronary obstruction on myocardial microvascular dysfunction in type 2 diabetes mellitus patients evaluated by first-pass perfusion CMR study
Authors: Wang Jin , Yang Zhi-Gang , Guo Ying-Kun , Jiang Yu , Yan Wei-Feng , Qian Wen-Lei , Fang Han , Min Chen-Yan , Li Yuan
Published: June 2023

Background

Type 2 diabetes mellitus (T2DM) frequently coexists with obstructive coronary artery disease (OCAD), which are at increased risk for cardiovascular morbidity and mortality. This study aimed to investigate the impact of coronary obstruction on myocardial microcirculation function in T2DM patients, and explore independent predictors of reduced coronary microvascular perfusion.

Methods

Cardiac magnetic resonance (CMR) scanning was performed on 297 T2DM patients {188 patients without OCAD [T2DM(OCAD −)] and 109 with [T2DM(OCAD +)]} and 89 control subjects. CMR-derived perfusion parameters, including upslope, max signal intensity (MaxSI), and time to maximum signal intensity (TTM) in global and segmental (basal, mid-ventricular, and apical slices) were measured and compared among observed groups. According to the median of Gensini score (64), T2DM(OCAD +) patients were subdivided into two groups. Univariable and multivariable linear regression analyses were performed to identify independent predictors of microcirculation dysfunction.

Results

T2DM(OCAD −) patients, when compared to control subjects, had reduced upslope and prolonged TTM in global and all of three slices (all P < 0.05). T2DM(OCAD +) patients showed a significantly more severe impairment of microvascular perfusion than T2DM(OCAD −) patients and control subjects with a more marked decline upslope and prolongation TTM in global and three slices (all P < 0.05). From control subjects, through T2DM(OCAD +) patients with Gensini score ≤ 64, to those patients with Gensini score > 64 group, the upslope declined and TTM prolonged progressively in global and mid-ventricular slice (all P < 0.05). The presence of OCAD was independently correlated with reduced global upslope (β =  − 0.104, P < 0.05) and global TTM (β = 0.105, P < 0.05) in patients with T2DM. Among T2DM(OCAD +) patients, Gensini score was associated with prolonged global TTM (r = 0.34, P < 0.001).

Conclusions

Coronary artery obstruction in the context of T2DM exacerbated myocardial microcirculation damage. The presence of OCAD and Gensini score were independent predictors of decreased microvascular function.

Trial registration: Retrospectively registered.
Better cardiac care – the patient experience – a qualitative study
Authors: Jennings Warren , Egert Sonya , Fisher Celestine , Renouf Sonia , Bryce Vivian , Grugan Sean , Wang William , Askew Deborah
Published: June 2023

Background

In 2015, a Brisbane tertiary hospital’s cardiac unit implemented a new model of multidisciplinary care (Better Cardiac Care (BCC)) for Aboriginal and Torres Strait Islander patients. Since then, clinical indicators for Aboriginal and Torres Strait Islander cardiac patients have improved, but the recipients’ voices have not been heard. This research aimed to determine the acceptability and appropriateness, features of value, and opportunities for improvements in this model of care, from the perspective of patients and their family members.

Methods

This descriptive qualitative study employed a narrative methodology. BCC Health Workers contacted prospective participants; with consent, interested individuals were then contacted by the Aboriginal Research Officer (RO) who arranged yarning sessions and consent. Family members were also invited to share their stories of their loved ones’ hospitalisation. Two researchers conducted the interviews, using a yarning approach. Inductive narrative analysis, informed by Aboriginal and Torres Strait Islander ways of Being, Knowing, and Doing, focused on enabling participants’ stories to be heard and understood from their perspectives.

Results

Relationality was at the heart of the BCC model of care, particularly between patients and Aboriginal and Torres Strait Islander staff. The relationality included a responsibility for holistic care, extending beyond hospital discharge, although support and handover for family members required improvement. The Aboriginal and Torres Strait Islander staff understood the contextual and structural challenges faced by participants, including the disempowerment and racism experienced in healthcare. This understanding was shared with the BCC team who, in turn, protected, advocated for, and holistically supported participants through their cardiac health journeys.

Conclusions

Empowering (and employing) Aboriginal and Torres Strait Islander staff, and relating to patients as people, enabled BCC to meet Aboriginal and Torres Strait Islander patient’s needs and improve outcomes. The wider health system and health academia could benefit from exploring and valuing Aboriginal and Torres Strait Islander discourses of relationality.
Impact of safer supply programs on injection practices: client and provider experiences in Ontario, Canada
Authors: Gagnon Marilou , Rudzinski Katherine , Guta Adrian , Schmidt Rose A. , Kryszajtys David T. , Kolla Gillian , Strike Carol
Published: June 2023

Objectives

Fentanyl has contributed to a sharp rise in the toxicity of the unregulated drug supply and fatal overdoses in Canada. It has also changed injection practices. Injection frequency has increased as a result and so has equipment sharing and health-related risks. The aim of this analysis was to explore the impact of safer supply programs on injection practices from the perspective of clients and providers in Ontario, Canada.

Methods

The data set included qualitative interviews with 52 clients and 21 providers that were conducted between February and October 2021 across four safer supply programs. Interview excerpts discussing injection practices were extracted, screened, coded and then grouped into themes.

Results

We identified three themes, each theme corresponding to a change in injection practices. The first change was a decrease in the amount of fentanyl used and a decrease in injection frequency. The second change involved switching to injecting hydromorphone tablets instead of fentanyl. Finally, the third change was stopping injecting altogether and taking safer supply medications orally.

Conclusion

Safer supply programs can contribute to reducing injection-related health risks in addition to overdose risks. More specifically, they have the potential to address disease prevention and health promotion gaps that stand-alone downstream harm reduction interventions cannot address, by working upstream and providing a safer alternative to fentanyl.
Intrahepatic macrophage reprogramming associated with lipid metabolism in hepatitis B virus-related acute-on-chronic liver failure
Authors: Peng Bo , Li Hao , Liu Kai , Zhang Pengpeng , Zhuang Quan , Li Junhui , Yang Min , Cheng Ke , Ming Yingzi
Published: June 2023

Background

Acute-on-chronic liver failure (ACLF) is a severe syndrome with high short-term mortality, but the pathophysiology still remains largely unknown. Immune dysregulation and metabolic disorders contribute to the progression of ACLF, but the crosstalk between immunity and metabolism during ACLF is less understood. This study aims to depict the immune microenvironment in the liver during ACLF, and explore the role of lipid metabolic disorder on immunity.

Methods

Single-cell RNA-sequencing (scRNA-seq) was performed using the liver non-parenchymal cells (NPCs) and peripheral blood mononuclear cells (PBMCs) from healthy controls, cirrhosis patients and ACLF patients. A series of inflammation-related cytokines and chemokines were detected using liver and plasma samples. The lipid metabolomics targeted free fatty acids (FFAs) in the liver was also detected.

Results

The scRNA-seq analysis of liver NPCs showed a significant increase of monocytes/macrophages (Mono/Mac) infiltration in ACLF livers, whereas the resident Kupffer cells (KCs) were exhausted. A characterized TREM2+ Mono/Mac subpopulation was identified in ACLF, and showed immunosuppressive function. Combined with the scRNA-seq data from PBMCs, the pseudotime analysis revealed that the TREM2+ Mono/Mac were differentiated from the peripheral monocytes and correlated with lipid metabolism-related genes including APOE, APOC1, FABP5 and TREM2. The targeted lipid metabolomics proved the accumulation of unsaturated FFAs associated with α-linolenic acid (α-LA) and α-LA metabolism and beta oxidation of very long chain fatty acids in the ACLF livers, indicating that unsaturated FFAs might promote the differentiation of TREM2+ Mono/Mac during ACLF.

Conclusions

The reprogramming of macrophages was found in the liver during ACLF. The immunosuppressive TREM2+ macrophages were enriched in the ACLF liver and contributed to the immunosuppressive hepatic microenvironment. The accumulation of unsaturated FFAs in the ACLF liver promoted the reprogramming of the macrophages. It might be a potential target to improve the immune deficiency of ACLF patients through regulating lipid metabolism.
Long term sequelae after SARS-CoV-2 infection in children: a household study
Authors: Sluiter-Post Judith G. C. , Fourie Elandri , Wildenbeest Joanne G. , van Lelyveld Steven F. L. , Bruijning-Verhagen Patricia C. J. L. , van Houten Marianne A.
Published: June 2023

Background

In children persistent symptoms after SARS-CoV-2 infection have been reported, however, duration and characteristics of symptoms in previously healthy children remain unclear. Therefore this study aimed to evaluate persisting symptoms in children at 6 and 12 months after a SARS-CoV-2 infection.

Methods

In this prospective cohort study households with a confirmed SARS-CoV-2 positive outbreak were matched 1:1 to household controls from SARS-CoV-2 negative outbreaks. These households completed questionnaires at 6 and 12 months on the presence and severity of SARS-CoV-2 related symptoms, general well-being/functioning, cognition, persisting symptoms and quality of life.

Findings

None of the children who had a SARS-CoV-2 infection during the study reported persistent symptoms at 6 and 12 months after infection, whereas almost 8% of the children with a negative RT-PCR test during the study reported symptoms such as coughing and mild fever, however, no significant differences were found. In addition, for all other outcomes, no differences were observed between the two groups.

Take home message

Post-acute sequelae of mild SARS-CoV-2 infections appears to be uncommon in previously healthy children.
Ethical challenges and dilemmas in the rationing of health commodities and provision of high-risk clinical services during COVID-19 pandemic in Ethiopia: the experiences of frontline health workers
Authors: Melaku Tsegaye , Zeynudin Ahmed , Suleman Sultan
Published: June 2023

Background

Ethical reasoning and sensitivity are always important in public health, but it is especially important in the sensitive and complex area of public health emergency preparedness. Here, we explored the ethical challenges, and dilemmas encountered by frontline health workers amid the coronavirus disease-19 (COVID-19) pandemic in Ethiopia.

Methods

A nationwide survey was conducted amongst the frontline health workers from nineteen public hospitals. Health workers were invited to respond to a self-administered questionnaire. Data were weighted and analyzed using descriptive statistics.

Results

Of the 285 frontline health workers to whom questionnaires were distributed, 217 of them gave their responses (response rate 76.1%). Respondents frequently reported encountering rationing dilemmas on health commodities directly used for the prevention and treatment of COVID-19. Most (83.9%) of the health workers agreed that they encountered ethical challenges very frequently or frequently. Almost all [215(99.1%)] claimed that the limitation of resources was directly used for the treatment and prevention of COVID-19. The frequency of difficulty in the provision of essential clinical services varied between 77% and 98.7% for different services. More than half of the study participants reported that they had encountered difficulty in the provision of clinical care on a daily or weekly basis. Regarding rationing strategies, isolating COVID-19 treatment units and limiting admission were the most frequent rationing strategies used by two-thirds of health workers on a daily or weekly basis.

Conclusion

Front-line health workers encountered numerous ethically challenging situations during COVID-19. More than half of health workers reported that they encountered ethical challenges in rationing the resources and delivery of different clinical services such as family planning services, maternal and childcare, immunization, and chronic care. With limited resources such as ventilators and hospital beds, healthcare providers have been faced with the difficult task of deciding who gets access to these resources and who doesn't. Overall, the COVID-19 pandemic has presented numerous ethical challenges for healthcare providers, highlighting the importance of ethical considerations in healthcare delivery. By being aware of these dilemmas and having policies in place to address them, healthcare providers can ensure that they are providing the best possible care to their patients while upholding ethical standards.
Epigenetic reprogramming-induced guanidinoacetic acid synthesis promotes pancreatic cancer metastasis and transcription-activating histone modifications
Authors: Yang Jinshou , Ren Bo , Ren Jie , Yang Gang , Fang Yuan , Wang Xing , Zhou Feihan , You Lei , Zhao Yupei
Published: June 2023

Background

Pancreatic ductal adenocarcinoma (PDAC) tends to undergo distant metastasis, especially liver metastasis, leading to a poor prognosis. Metabolic remodelling and epigenetic reprogramming are two important hallmarks of malignant tumours and participate in regulating PDAC tumorigenesis and metastasis. However, the interaction between these two processes during PDAC metastasis has not been fully elucidated.

Methods

We performed metabolomics analysis to identify the critical metabolites associated with PDAC liver metastasis and focused on guanidinoacetic acid (GAA). Intracellular GAA content was significantly increased in liver metastatic PDAC cells compared to primary cancer cells in mouse xenograft tumour models. The effects of GAA supplementation and glycine amidinotransferase (GATM) knockdown on PDAC metastasis were assessed by analysing cell migration, filopodia formation, epithelial-mesenchymal transition (EMT), and in vivo metastasis in different cell and animal models. Next, ChIP‒qPCR, 3C‒qPCR, and CRISPRi/dCas9-KRAB experiments were used to validate the “epigenome-metabolome" mechanism. Finally, the results of in vitro approaches, including RNA-seq, CUT&RUN, RT‒qPCR, and western blot analyses, as well as luciferase reporter gene assay and transwell assay, revealed the GAA-c-Myc-HMGA axis and transcription-activating histone modifications reprogramming.

Results

A high level of intracellular GAA was associated with PDAC liver metastasis. GAA could promote the migration, EMT, and liver metastasis of pancreatic cancer cells in vitro and in vivo. Next, we explored the role of GATM-mediated de novo GAA synthesis in pancreatic cancer metastasis. High expression of GATM was positively correlated with advanced N stage in PDAC. Knockdown of GATM significantly reduced the intracellular level of GAA, suppressed EMT, and inhibited PDAC liver metastasis, and these effects were attenuated by GAA supplementation. Mechanistically, we identified the active enhancers looped to the Gatm gene locus that promoted GATM expression and PDAC liver metastasis. Furthermore, we found that GAA promoted cell migration and EMT by regulating c-Myc-mediated high mobility group AT-hook protein expression. Moreover, GAA increased the H3K4me3 modification level by upregulating histone methyltransferases, which induced the transcription of metastasis-related genes, including Myc.

Conclusions

These findings revealed the critical role of the epigenome-metabolome interaction in regulating PDAC liver metastasis and suggested potential therapeutic strategies targeting GAA metabolism and epigenetic regulatory mechanisms.
The effects of metformin on anti-Müllerian hormone levels in patients with polycystic ovary syndrome: a systematic review and meta-analysis
Authors: Zhou Zhijiao , Chen Hongzhi , Chu Ling , Zou Qiong , Chen Qian , Yang Jun , Liu Yang , Ou Xiang
Published: June 2023

Objective

To analyze whether metformin treatment in patients with polycystic ovary syndrome (PCOS) results in a decrease of anti-Müllerian hormone (AMH) levels, we reviewed and analyzed PCOS studies which evaluated serum AMH levels before and after metformin treatment.

Methods

This is a systematic review and meta-analysis of self-controlled clinical trials. Databases including PubMed, Embase, and Web of Science library were searched to identify eligible studies published before February 2023. Random-effects models were applied to assess standardized mean differences (SMDs) with 95% confidence intervals (95% CI).

Results

The electronic-based search retrieved 167 articles of which 14 studies (12 publications) involving 257 women with PCOS were included. In general, AMH levels decreased significantly after metformin treatment [SMD (95% CI) of -0.70 (-1.13 to -0.28); P = 0.001]. Metformin exhibited a strong inhibitory effect on AMH levels for PCOS patients with age less than 28 [SMD − 1.24, 95% CI − 2.15 to − 0.32, P = 0.008]. Additionally, AMH levels significantly slid down in PCOS patients with no more than 6 months metformin treatment [SMD − 1.38, 95% CI − 2.18 to − 0.58, P = 0.0007], or with no more than a dose of 2000 mg/day [SMD -0.70, 95% CI -1.11 to -0.28; P = 0.001]. Notably, suppressive effects of metformin treatment were merely observed in patients with AMH levels at baseline higher than 4.7 ng/ml [SMD − 0.66, 95% CI − 1.02 to − 0.31, P = 0.0003].

Conclusion

This meta-analysis provided quantitative evidence demonstrating that metformin significantly decreased AMH levels, especially for young patients and those with AMH levels at baseline higher than 4.7 ng/ml.

Trial registration

PROSPERO CRD42020149182.
RAD21 is the core subunit of the cohesin complex involved in directing genome organization
Authors: Sun Yuao , Xu Xin , Zhao Wenxue , Zhang Yu , Chen Keyang , Li Yongzheng , Wang Xiaotian , Zhang Mengling , Xue Boxin , Yu Wanting , Hou Yingping , Wang Chaobin , Xie Wei , Li Cheng , Kong Daochun , Wang Shu , Sun Yujie
Published: June 2023

Background

The ring-shaped cohesin complex is an important factor for the formation of chromatin loops and topologically associating domains (TADs) by loop extrusion. However, the regulation of association between cohesin and chromatin is poorly understood. In this study, we use super-resolution imaging to reveal the unique role of cohesin subunit RAD21 in cohesin loading and chromatin structure regulation.

Results

We directly visualize that up-regulation of RAD21 leads to excessive chromatin loop extrusion into a vermicelli-like morphology with RAD21 clustered into foci and excessively loaded cohesin bow-tying a TAD to form a beads-on-a-string-type pattern. In contrast, up-regulation of the other four cohesin subunits results in even distributions. Mechanistically, we identify that the essential role of RAD21 is attributed to the RAD21-loader interaction, which facilitates the cohesin loading process rather than increasing the abundance of cohesin complex upon up-regulation of RAD21. Furthermore, Hi-C and genomic analysis reveal how RAD21 up-regulation affects genome-wide higher-order chromatin structure. Accumulated contacts are shown at TAD corners while inter-TAD interactions increase after vermicelli formation. Importantly, we find that in breast cancer cells, the expression of RAD21 is aberrantly high with poor patient survival and RAD21 forms beads in the nucleus. Up-regulated RAD21 in HeLa cells leads to compartment switching and up-regulation of cancer-related genes.

Conclusions

Our results provide key insights into the molecular mechanism by which RAD21 facilitates the cohesin loading process and provide an explanation to how cohesin and loader work cooperatively to promote chromatin extrusion, which has important implications in construction of three-dimensional genome organization.
Exploratory analysis of L1 retrotransposons expression in autism﻿
Authors: Spirito Giovanni , Filosi Michele , Domenici Enrico , Mangoni Damiano , Gustincich Stefano , Sanges Remo
Published: June 2023

Background

Autism spectrum disorder (ASD) is a set of highly heterogeneous neurodevelopmental diseases whose genetic etiology is not completely understood. Several investigations have relied on transcriptome analysis from peripheral tissues to dissect ASD into homogenous molecular phenotypes. Recently, analysis of changes in gene expression from postmortem brain tissues has identified sets of genes that are involved in pathways previously associated with ASD etiology. In addition to protein-coding transcripts, the human transcriptome is composed by a large set of non-coding RNAs and transposable elements (TEs). Advancements in sequencing technologies have proven that TEs can be transcribed in a regulated fashion, and their dysregulation might have a role in brain diseases.

Methods

We exploited published datasets comprising RNA-seq data from (1) postmortem brain of ASD subjects, (2) in vitro cell cultures where ten different ASD-relevant genes were knocked out and (3) blood of discordant siblings. We measured the expression levels of evolutionarily young full-length transposable L1 elements and characterized the genomic location of deregulated L1s assessing their potential impact on the transcription of ASD-relevant genes. We analyzed every sample independently, avoiding to pool together the disease subjects to unmask the heterogeneity of the molecular phenotypes.

Results

We detected a strong upregulation of intronic full-length L1s in a subset of postmortem brain samples and in in vitro differentiated neurons from iPSC knocked out for ATRX. L1 upregulation correlated with an high number of deregulated genes and retained introns. In the anterior cingulate cortex of one subject, a small number of significantly upregulated L1s overlapped with ASD-relevant genes that were significantly downregulated, suggesting the possible existence of a negative effect of L1 transcription on host transcripts.

Limitations

Our analyses must be considered exploratory and will need to be validated in bigger cohorts. The main limitation is given by the small sample size and by the lack of replicates for postmortem brain samples. Measuring the transcription of locus-specific TEs is complicated by the repetitive nature of their sequence, which reduces the accuracy in mapping sequencing reads to the correct genomic locus.

Conclusions

L1 upregulation in ASD appears to be limited to a subset of subjects that are also characterized by a general deregulation of the expression of canonical genes and an increase in intron retention. In some samples from the anterior cingulate cortex, L1s upregulation seems to directly impair the expression of some ASD-relevant genes by a still unknown mechanism. L1s upregulation may therefore identify a group of ASD subjects with common molecular features and helps stratifying individuals for novel strategies of therapeutic intervention.