bluuebunny/crossref_metadata_2025 huggingface dataset:
Uneven regional distribution earthquake danger zones and of cell towers and cells in Türkiye
Authors: Erdem Umut
Published: February 2024

Zoning potential danger derived from earthquakes is crucial for the development of policies dealing with the future of the cities. Determination of the potential danger zones regarding earthquakes with the telecommunication infrastructure is crucial for the development of policies dealing with the future of the cities. By utilizing the cartogram mapping technique, this paper aims to display potential earthquake danger zones with the uneven distribution of the cell towers and cells on a population cartogram for Türkiye. This is crucial for the cities regarding the future potential communication crises after disasters. Policymakers should provide and develop well-functioning communication networks (GSM networks) for the organization of aid and search and rescue operations since the collapse of the communication infrastructure renders all post-disaster processes insoluble and dysfunctional.
The Pigeon as a Model of Complex Visual Processing and Category Learning
Authors: Wasserman Edward A , Turner Brandon M , Güntürkün Onur
Published: February 2024

Over the past 30 years, behavioral, computational, and neuroscientific investigations have yielded fresh insights into how pigeons adapt to the diverse complexities of their visual world. A prime area of interest has been how pigeons categorize the innumerable individual stimuli they encounter. Most studies involve either photorealistic representations of actual objects thus affording the virtue of being naturalistic, or highly artificial stimuli thus affording the virtue of being experimentally manipulable. Together those studies have revealed the pigeon to be a prodigious classifier of both naturalistic and artificial visual stimuli. In each case, new computational models suggest that elementary associative learning lies at the root of the pigeon’s category learning and generalization. In addition, ongoing computational and neuroscientific investigations suggest how naturalistic and artificial stimuli may be processed along the pigeon’s visual pathway. Given the pigeon’s availability and affordability, there are compelling reasons for this animal model to gain increasing prominence in contemporary neuroscientific research.
Interactive Word Walls in Music Classrooms
Authors: Hatch Emily
Published: February 2024

Word walls are an important element in teaching students how to describe music and use academic vocabulary in authentic ways. This article will explore what word walls are; different forms that word walls can take in the classroom; and ways to increase the interactivity of word walls to promote student learning.
Preclinical models of maternal asthma and progeny outcomes: a scoping review
Authors: Robinson Joshua L. , Gatford Kathryn L. , Bailey Danielle N. , Roff Andrea J. , Clifton Vicki L. , Morrison Janna L. , Stark Michael J.
Published: February 2024

There is an increased risk of adverse perinatal outcomes in the ∼17% of women with asthma during pregnancy. The mechanisms linking maternal asthma and adverse outcomes are largely unknown, but reflect joint effects of genetics and prenatal exposure to maternal asthma. Animal models are essential to understand the underlying mechanisms independent of genetics and comorbidities, and enable safe testing of interventions. This scoping review aimed to explore the methodology, phenotype, characteristics, outcomes and quality of published studies using preclinical maternal asthma models. MEDLINE (PubMed), Embase (Elsevier) and Web of Science were systematically searched using previously validated search strings for maternal asthma and for animal models. Two reviewers independently screened titles and abstracts, full texts, and then extracted and assessed the quality of each study using the Animal Research: Reporting ofIn VivoExperiments (ARRIVE) 2.0 guidelines. Out of 3618 studies identified, 39 were eligible for extraction. Most studies were in rodents (86%) and all were models of allergic asthma. Maternal and progeny outcomes included airway hyperresponsiveness, airway resistance, inflammation, lung immune cells, lung structure and serum immunoglobulins and cytokines. Experimental design (100%), procedural details (97%) and rationale (100%) were most often reported. Conversely, data exclusion (21%), blinding (18%) and adverse events (8%) were reported in a minority of studies. Species differences in physiology and timing of development, the use of allergens not relevant to humans and a lack of comparable outcome measures may impede clinical translation. Future studies exploring models of maternal asthma should adhere to the minimum core outcomes set presented in this review.
Reverse shoulder arthroplasty with a 155° neck-shaft angle inlay implant design without reattachment of the subscapularis tendon results in satisfactory functional internal rotation and no instability: a cohort study
Authors: Macken Arno A. , van der Poel Wouter J. , Buijze Geert A. , Beckers Joris J. , Eygendaal Denise , Lafosse Laurent , Lafosse Thibault
Published: February 2024

Background

The aim of this study was to use the Activities of Daily Living which require Internal Rotation (ADLIR) questionnaire to assess the functional internal rotation in patients who had undergone reverse shoulder arthroplasty (RSA) without reattachment of the subscapularis (SSc) tendon at a minimum follow-up of 2 years. The secondary aim was to report the objective range of motion (ROM) and the rate of postoperative instability.

Materials and methods

All consecutive primary RSA procedures without reattachment of the SSc tendon that were performed using a Delta Xtend prosthesis (an inlay system with a 155° neck-shaft angle) between January 2015 and December 2020 were identified to ensure a minimum follow-up of 2 years. Patients were contacted and requested to fill in several questionnaires, including the ADLIR and Auto-Constant scores.

Results

In total, 210 patients met the inclusion criteria; among those patients, 187 could be contacted and 151 completed questionnaires (response rate: 81%). The SSc tendon was fully detached without repair in all cases, and a superolateral approach was used in 130 (86%) cases. The median follow-up was 4.5 years (range: 2.0–7.6). At final follow-up, the mean ADLIR score was 88/100 (interquartile range (IQR): 81–96). The median level reached in internal rotation was the 3rd lumbar vertebra (IQR: lumbosacral region—12th thoracic vertebra). Of the 210 eligible patients, one required a revision for a dislocation within the first month after primary surgery. With regards to regression analysis with ADLIR score as the outcome, none of the factors were associated with the ADLIR score, although age and smoking approached significance (0.0677 and 0.0594, respectively). None of the explanatory variables were associated with ROM in internal rotation (p > 0.05).

Conclusions

This study demonstrates that satisfactory ADLIR scores and internal rotation ROM were obtained at mid-term follow-up after RSA leaving the SSc detached. Leaving the SSc detached also did not lead to high instability rates; only one out of 210 prostheses was revised for dislocation within the first month after primary surgery.

Level of evidence III.
The structure and diversity of bacteria and fungi in the roots and rhizosphere soil of three different species of Geodorum
Authors: Liu Jianxiu , Zeng Danjuan , Huang Yang , Zhong Lisha , Liao Jialin , Shi Yuxing , Jiang Haidu , Luo Yajin , Liang Yu , Chai Shengfeng
Published: February 2024

Shepherd's crook (Geodorum) is a genus of protected orchids that are valuable both medicinally and ornamentally. Geodorum eulophioides (GE) is an endangered and narrowly distributed species, and Geodorum densiflorum (GD) and Geodorum attenuatum (GA) are widespread species. The growth of orchids depend on microorganisms. However, there are few studies on the microbial structure in Geodorum, and little is known about the roles of microorganisms in the endangered mechanism of G. eulophioides. This study analyzed the structure and composition of bacterial and fungal communities in the roots and rhizosphere soil of GE, GD, and GA. The results showed that Delftia, Bordetella and norank_f_Xanthobacteraceae were the dominant bacteria in the roots of Geodorum, while norank_f_Xanthobacteraceae, Gaiella and norank_f_norank_o_Gaiellales were the dominant bacteria in the rhizosphere soil of Geodorum. In the roots, the proportion of Mycobacterium in GD_roadside was higher than that in GD_understory, on the contrary, the proportion of Fusarium, Delftia and Bordetella in GD_roadside was lower than that in GD_understory. Compared with the GD_understory, the roots of GD_roadside had lower microbial diversity. In the endangered species GE, Russula was the primary fungus in the roots and rhizosphere soil, with fungal diversity lower than in the more widespread species. Among the widespread species, the dominant fungal genera in the roots and rhizosphere soil were Neocosmospora, Fusarium and Coprinopsis. This study enhances our understanding of microbial composition and diversity, providing fundamental information for future research on microbial contributions to plant growth and ecosystem function in Geodorum.
Development of non-alcoholic steatohepatitis is associated with gut microbiota but not with oxysterol enzymes CH25H, EBI2, or CYP7B1 in mice
Authors: Wyss Jacqueline , Raselli Tina , Wyss Annika , Telzerow Anja , Rogler Gerhard , Krupka Niklas , Yilmaz Bahtiyar , Schmidt Thomas S. B. , Misselwitz Benjamin
Published: February 2024

Liver steatosis is the most frequent liver disorder and its advanced stage, non-alcoholic steatohepatitis (NASH), will soon become the main reason for liver fibrosis and cirrhosis. The “multiple hits hypothesis” suggests that progression from simple steatosis to NASH is triggered by multiple factors including the gut microbiota composition. The Epstein Barr virus induced gene 2 (EBI2) is a receptor for the oxysterol 7a, 25-dihydroxycholesterol synthesized by the enzymes CH25H and CYP7B1. EBI2 and its ligand control activation of immune cells in secondary lymphoid organs and the gut. Here we show a concurrent study of the microbial dysregulation and perturbation of the EBI2 axis in a mice model of NASH.

We used mice with wildtype, or littermates with CH25H−/−, EBI2−/−, or CYP7B1−/− genotypes fed with a high-fat diet (HFD) containing high amounts of fat, cholesterol, and fructose for 20 weeks to induce liver steatosis and NASH. Fecal and small intestinal microbiota samples were collected, and microbiota signatures were compared according to genotype and NASH disease state.

We found pronounced differences in microbiota composition of mice with HFD developing NASH compared to mice did not developing NASH. In mice with NASH, we identified significantly increased 33 taxa mainly belonging to the Clostridiales order and/ or the family, and significantly decreased 17 taxa. Using an Elastic Net algorithm, we suggest a microbiota signature that predicts NASH in animals with a HFD from the microbiota composition with moderate accuracy (area under the receiver operator characteristics curve = 0.64). In contrast, no microbiota differences regarding the studied genotypes (wildtype vs knock-out CH25H−/−, EBI2−/−, or CYP7B1−/−) were observed.

In conclusion, our data confirm previous studies identifying the intestinal microbiota composition as a relevant marker for NASH pathogenesis. Further, no link of the EBI2 – oxysterol axis to the intestinal microbiota was detectable in the current study.
Vermicompost as an alternative substrate to peat moss for strawberry (Fragaria ananassa) in soilles culture
Authors: Azizi Yeganeh Mahsa , Shahabi Ali Asghar , Ebadi Ali , Abdossi Vahid
Published: February 2024

Background

Consecutive droughts and quantitative and qualitative reduction of surface and underground water resources have caused an increase in greenhouse and hydroponic cultivation for most garden crops, including strawberries, in Iran. On the other hand, most of the inputs of greenhouse crops in Iran are imported. To possibility of replacing vermicompost with peat moss under hydroponic cultivation, an experiment was done in a split plot based on randomized complete blocks design in three replications in Isfahan (Iran) Agricultural and Natural Resources Research Center in 2019. The main treatment was substrate at four levels included different levels of vermicompost (30 and 50%) and peat moss (30 and 50%) in combination with perlite and sub-treatment were Selva and Camarosa cultivars.

Results

The results showed that Camarosa cultivar and Selva cultivar in (perlite/ peat moss 50:50) and Selva cultivar in (perlite / vermicompost 70:30) had maximum yield.

Leaf number and chlorophyll index were maximum in Camarosa cultivar in peat moss substrates. Strawberry cultivars had the highest root fresh weight, the content of vitamin C and total soluble solids (TSS) in substrates containing vermicompost. Camarosa cultivar in (perlite / peat moss50:50) and Selva cultivar in (perlite /vermicompost 50:50) had maximum root dry weight. Also, the highest number of inflorescences was related to substrates containing peat moss and (perlite /vermicompost 70:30). Maximum amount of fresh and dry weight of shoots were observed in (perlite/ peat moss70:30). Selva cultivar had more inflorescences (16.5%) than Camarosa cultivar and Camarosa cultivar produced more fresh and dry weight of shoots (16.5%, 23.01%) than Selva cultivar.

Conclusion

Expriment results highlighted the importance of considering both main and sub-treatments in agricultural research, as they interacted to influence various growth and yield parameters. 50% vermicompost treatment combined with perlite had a positive impact on plant growth and in quality index such as vitamin C content and TSS was highest. while the choice of cultivar affected different aspects of plant development. Selva cultivar was known to be more tolerant to salinity caused by vermicompost. Vermicompost is local and more economical, also salt resistant cultivars are recommended in a controlled (30%) amount of vermicompost.
Transcription factor encoding gene OsC1 regulates leaf sheath color through anthocyanidin metabolism in Oryza rufipogon and Oryza sativa
Authors: Jiang Liqun , Lyu Shuwei , Yu Hang , Zhang Jing , Sun Bingrui , Liu Qing , Mao Xingxue , Chen Pingli , Pan Dajian , Chen Wenfeng , Fan Zhilan , Li Chen
Published: February 2024

Carbohydrates, proteins, lipids, minerals and vitamins are nutrient substances commonly seen in rice grains, but anthocyanidin, with benefit for plant growth and animal health, exists mainly in the common wild rice but hardly in the cultivated rice. To screen the rice germplasm with high intensity of anthocyanidins and identify the variations, we used metabolomics technique and detected significant different accumulation of anthocyanidins in common wild rice (Oryza rufipogon, with purple leaf sheath) and cultivated rice (Oryza sativa, with green leaf sheath). In this study, we identified and characterized a well-known MYB transcription factor, OsC1, through phenotypic (leaf sheath color) and metabolic (metabolite profiling) genome-wide association studies (pGWAS and mGWAS) in 160 common wild rice (O. rufipogon) and 151 cultivated (O. sativa) rice varieties. Transgenic experiments demonstrated that biosynthesis and accumulation of cyanidin-3-Galc, cyanidin 3-O-rutinoside and cyanidin O-syringic acid, as well as purple pigmentation in leaf sheath were regulated by OsC1. A total of 25 sequence variations of OsC1 constructed 16 functional haplotypes (higher accumulation of the three anthocyanidin types within purple leaf sheath) and 9 non-functional haplotypes (less accumulation of anthocyanidins within green leaf sheath). Three haplotypes of OsC1 were newly identified in our germplasm, which have potential values in functional genomics and molecular breeding of rice. Gene-to-metabolite analysis by mGWAS and pGWAS provides a useful and efficient tool for functional gene identification and omics-based crop genetic improvement.
Physical work environment and burnout among primary care physicians in Israel: a cross-sectional study
Authors: Bentulila Yaara , Lev Shalem Liat , Cohen Bar , Adler Limor
Published: February 2024

Background

Physician burnout remains a prevalent issue globally, negatively affecting work satisfaction and patient care. However, exploration of the physical work environments of physicians, a potential influencing factor for burnout, remains scarce. The physical work environment is everything that surrounds the physician, including the doctor’s office, the clinic, the clinic’s building, the waiting, and staff rooms. The aims of this study were to describe aspects of the physical work environment of primary care physicians (PCPs) and to explore the association between the physical work environment and burnout.

Methods

In this cross-sectional study, we emailed questionnaires to an online community of PCPs in Israel in October 2021. We asked physicians about their satisfaction with their physical work environment, evaluated elements of the work environment, and assessed burnout status (with the Shirom-Melamed Burnout Measure, SMBM). We used the Chi-square and Mann-Witney tests to compare categorical and continuous variables and used logistic regression for the final model.

Results

Two hundred twenty-one PCPs answered the questionnaire (27.6% response rate). Over a third (35.7%) of respondents reported high burnout. PCPs who were satisfied with their general physical environment had lower burnout rates than those who were unsatisfied (28.1% vs. 47.8%, p-value < 0.001). We found positive correlations between general satisfaction with the physical work environment and the scores achieved for the doctor’s office, the clinic, the clinic’s building, and the waiting room. In the multivariate analysis, high satisfaction with the general physical work environment was associated with decreased odds for burnout (OR-0.50, 95% CI 0.25–0.99, p-value-0.048).

Conclusion

The doctor’s office, the clinic, the clinic’s building, and the waiting room affected general satisfaction from the physical work environment. High satisfaction with the physical work environment reduced burnout rates. Future studies are needed to determine whether PCPs and managers should invest in the physical work environment to decrease burnout and increase satisfaction.
Improving adolescents’ dietary behavior through teacher-delivered cancer prevention education: a school-based cluster randomized intervention trial in urban Rajasthan
Authors: Mittal Ankit , Rustagi Neeti , Thirunavukkarasu Prasanna , Ghosh Santu , Raghav Pankaja
Published: February 2024

Background

Dietary practices are one of the most common modifiable risk factors for cancers. Foods rich in dietary fibers are considered protective, meanwhile fast & junk foods are risk for common cancers. Adolescence period is marked by habit formation and is thus suited for delivering behavioral intervention. Schools offer an optimal setting for planning and executing these interventions to a large number of adolescents.

Objective

To assess the effectiveness of a teacher-delivered cancer-prevention education in changing dietary behaviors of school going adolescents.

Methods

A cluster randomized trial was conducted in government secondary and senior secondary schools with schools as clusters. A minimum required sample of 1032 students was estimated from 16 schools with 1:1 allocation in intervention and non-intervention groups. Dietary behaviors were recorded as dichotomous variable. The determinants were recorded as per theory of planned behavior framework using Likert-scale. Two teachers from each intervention school were trained to deliver cancer prevention education with focus on role of dietary behavior. Pre-post training assessment of teachers’ knowledge towards common cancers was done using a self-administered questionnaire. Gender adjusted difference-in-difference analysis was done to assess intervention effect on both healthy and unhealthy behaviors.

Results

In selected schools all students from classes 8 to 10 were approached and a total of 1224 students were enrolled, of whom 1096 completed the study. The study recorded significant improvement in scores of students from intervention group compared to non-intervention group for their attitude, subjective norms, perceived behavioral control and intention towards consuming healthy and avoiding unhealthy foods. The intervention was effective in significantly improving the proportion of students limiting fried/fast/packed food & sugar sweetened beverages (OR:1.51, 95%CI:1.08,2.12,p:0.017), and consuming fruits & vegetables daily (OR:1.55, 95%CI:1.08,2.22, p:0.017) while adjusting effect of gender.

Conclusion

Classroom-based cancer prevention education delivered through teachers during regular working hours is effective in improving dietary behaviors and its determinants among adolescent students. Thus, we recommend integrating a section focusing on the role of diet in cancer prevention and other lifestyle diseases in the existing school curriculum.

Trial Registration

The trial was registered under Clinical Trial Registry-India with registration number CTRI/2018/12/016586, dated-10/12/2018.
Global, regional, and national burdens of facial fractures: a systematic analysis of the global burden of Disease 2019
Authors: Zhang Ze-Xing , Xie Long , Li Zhi
Published: February 2024

Background

The incidence of facial fractures has undergone tremendous changes in recent years as a result of socio-economic development and aging populations. Currently, there is a lack of updated and comprehensive analyses of global trends and causes of facial fractures. The Global Burden of Disease (GBD) database is a product of a global research organization used to quantify the global impact of hundreds of diseases, injuries, and risk factors. The aim of this study was to update global burden of facial fractures from 1990 to 2019 by using the GBD2019.

Materials and methods

The present study extracted the global incidence, prevalence, and years lived with disability (YLDs) for facial fractures, as well as the age-standardized rates (ASRs) of these variables using the Global Burden of Disease (GBD) 2019 database. The estimated annual percentage change (EAPC) was used to assess the trends of ASRs.

Results

Between 1990 and 2019, the incidence of facial fractures increased from 8,943,707 to 10,676,340, but the age-standardized incidence rate (ASIR) decreased from 161.5 to 138.8 per 100,000. Prevalence and YLDs exhibited the same trend as incidence. Over the 30 years, the incidence of facial fractures was consistently greater in males than in females. However, females aged ˃ 75 years had higher fracture incidence rates than males aged ˃ 75 years in 2019. The leading cause of facial fractures was falls, and both the age-standardized prevalence rate (ASPR) and age-standardized years lived with disability rate (ASYR) of falls increased with age.

Conclusion

Facial fractures still represent a significant burden to the world. Incidence, prevalence and YLDs all showed increasing trends, while ASRs decreased gradually from 1990 to 2019. Enhancing the quality of facial fractures data is helpful for monitoring the burden of facial fractures.
Feasibility of a physical exercise intervention for patients on a palliative care unit: a critical analysis
Authors: Schwonke Inken , Freitag Nils , Aschendorf Paula , Wucharz Kerstin , Thieme Johanna , Appelmann Iris , Schumann Moritz , Elsner Frank
Published: February 2024

Background

Recent exercise intervention studies have shown promising results in improving quality of life (QoL) and physical function (PF) in diverse chronic disease and advanced cancer patients. However, the effects of structured exercise in palliative care patients, having different therapeutic needs, lower life expectancies and PFs remain unknown. This study primarily aimed to assess the feasibility of an exercise intervention with follow-up by analysing recruitment numbers, screening procedures, acceptability, preferences, and safety of the exercise intervention as well as retention in follow-up. Our secondary aims related to changes in QoL and PF.

Methods

This study comprised of a one-arm design without a control group. Over 6 months, every in-hospital palliative care unit (PCU) patient was screened for eligibility. Eligible patients were asked to participate in a 2-week exercise intervention consisting of resistance training and/or endurance training with moderate or high intensity based on personal preferences and a 4-week follow-up. Before and after the exercise intervention, QoL and PF were assessed and a qualitative interview after the intervention addressed expectations and experiences of the exercise intervention. For follow-up, patients were provided with information on independent training and after 1 and 4 weeks a QoL assessment and qualitative interview were conducted.

Results

Of 124 patients screened, 10 completed the intervention with an adherence rate of (80 ± 25%), of which 6 patients completed follow-up. Endurance training was the most performed training type and only a few minor adverse events occurred in certain or likely connection to the exercise intervention. While physical QoL and PF measured by arm curl strength and time up and go performance improved, mental QoL and the other PF tests remained unchanged.

Conclusion

Despite the challenges that were faced in our screening and testing process, that are specific to the palliative patient population with their unique therapeutic requirements and varying mental-/ physical capabilities, we discovered the 2-week exercise intervention to be feasible, safe, and well tolerated by palliative care patients. Moreover, it seems that short-term improvements in QoL and PF are possible. Further full scale studies are required to confirm our findings.

Trial registration

The study was retrospectively registered on 25.01.2022 in the German Clinical Trials Register (DRKS00027861)
Nurse anaesthetists’ experiences of student nurse anaesthetist learning during clinical practice: a qualitative interview study
Authors: Hedlund Jakob , Blomberg Karin , Hjelmqvist Hans , Jaensson Maria
Published: February 2024

Background

The professional role of a nurse anaesthetist involves taking a pedagogical approach towards students, including supervision during clinical practice. Although supervisors are facilitators of student learning, they are offered little training in adult learning principles. The aim of this study was to describe supervisors’ experience of student nurse anaesthetist learning during clinical practice in the operating room.

Method

In this qualitative interview study, 12 semi-structured individual interviews were carried out with clinical supervising nurse anaesthetists. The data were analysed inductively using thematic analysis.

Results

The results are illustrated with one theme and five sub-themes. The clinical learning situation of student nurse anaesthetists is described as a reflection of different cultures coming together. The operating room environment is a new context to students, and students enter with different clinical background and experiences. There is tension in facilitating student learning due to demands for productivity; supervisors suggest the use of separate operating rooms with a special focus on learning in the future.

Conclusion

Clinical practice facilitates student learning and is a parallel process to routine care. Thus, it requires the cultures of higher education and healthcare organizations to co-exist. This is illustrated with the theme “Contributing to students’ future professional roles by bridging the hospital and university cultures”. In the operating room, student learning is challenged by a new context and time pressure as shown by subthemes. To overcome challenges and support student learning in the operating room from a supervisors’ perspective, interprofessional student teams are suggested as a future approach and need to be further investigated.
An integrated primary care service to reduce cardiovascular disease risk in people with severe mental illness: Primrose-A - thematic analysis of its acceptability, feasibility, and implementation
Authors: Shaw Philippa , Mifsud Annabel , Osborn David , Nahata Nitisha , Hall Cerdic , Prenelle Ian , Lamb Danielle
Published: February 2024

Background

Cardiovascular disease among patients with severe mental illness in England is a major preventable contributor to premature mortality. To address this, a nurse and peer-coach delivered service (Primrose-A) was implemented in three London general practices from 2019 (implementation continued during COVID-19). This study aimed to conduct interviews with patient and staff to determine the acceptability of, and experiences with, Primrose-A.

Methods

Semi-structured audio-recorded interviews with eight patients who had received Primrose-A, and 3 nurses, 1 GP, and 1 peer-coach who had delivered Primrose-A in three London-based GP surgeries were conducted. Reflexive thematic analysis was used to identify themes from the transcribed interviews.

Findings

Overall, Primrose-A was viewed positively by patients and staff, with participants describing success in improving patients’ mental health, isolation, motivation, and physical health. Therapeutic relationships between staff and patients, and long regular appointments were important facilitators of patient engagement and acceptance of the intervention. Several barriers to the implementation of Primrose-A were identified, including training, administrative and communication issues, burden of time and resources, and COVID-19.

Conclusions

Intervention acceptability could be enhanced by providing longer-term continuity of care paired with more peer-coaching sessions to build positive relationships and facilitate sustained health behaviour change. Future implementation of Primrose-A or similar interventions should consider: (1) training sufficiency (covering physical and mental health, including addiction), (2) adequate staffing to deliver the intervention, (3) facilitation of clear communication pathways between staff, and (4) supporting administrative processes.
Digitally-mediated coordination in healthcare: the effects of teleconsultation on doctor-to-doctor relational coordination
Authors: Olive Mattia Vincenzo , Gastaldi Luca , Corso Mariano
Published: February 2024

Background

Digitalization transforms the way in which interdependent work is coordinated, especially in healthcare settings. This work deepens the effect of teleconsultation use on health professionals’ coordination. For this aim, we rely on Relational Coordination Theory (RCT), which explores coordination as an interactive process among group participants within the context of task interdependency.

Methods

We collected data through an online survey administered to Italian specialist doctors between March and April 2023. 489 complete answers were gathered. Hypotheses have been tested through Structural Equation Modelling.

Results

We found that teleconsultation frequency of use has a positive and significant effect on both components of relational coordination, confirming our hypotheses.

Conclusions

Theoretically, this research contributes to our understanding of the effect of digitally mediated coordination mechanisms on relational coordination. In practice, we shed light on the organizational implications of telemedicine under a novel perspective, focusing on the role of professional interactions in digitally mediated work and providing useful elements for the organizational design of telemedicine.
Association between different insulin resistance surrogates and all-cause mortality in patients with coronary heart disease and hypertension: NHANES longitudinal cohort study
Authors: Hou Xin-Zheng , Lv Yan-Fei , Li Yu-Shan , Wu Qian , Lv Qian-Yu , Yang Ying-Tian , Li Lan-Lan , Ye Xue-Jiao , Yang Chen-Yan , Wang Man-Shi , Cao Lin-Lin , Wang Shi-Han
Published: February 2024

Background

Studies on the relationship between insulin resistance (IR) surrogates and long-term all-cause mortality in patients with coronary heart disease (CHD) and hypertension are lacking. This study aimed to explore the relationship between different IR surrogates and all-cause mortality and identify valuable predictors of survival status in this population.

Methods

The data came from the National Health and Nutrition Examination Survey (NHANES 2001–2018) and National Death Index (NDI). Multivariate Cox regression and restricted cubic splines (RCS) were performed to evaluate the relationship between homeostatic model assessment of IR (HOMA-IR), triglyceride glucose index (TyG index), triglyceride glucose-body mass index (TyG-BMI index) and all-cause mortality. The recursive algorithm was conducted to calculate inflection points when segmenting effects were found. Then, segmented Kaplan–Meier analysis, LogRank tests, and multivariable Cox regression were carried out. Receiver operating characteristic (ROC) and calibration curves were drawn to evaluate the differentiation and accuracy of IR surrogates in predicting the all-cause mortality. Stratified analysis and interaction tests were conducted according to age, gender, diabetes, cancer, hypoglycemic and lipid-lowering drug use.

Results

1126 participants were included in the study. During the median follow-up of 76 months, 455 participants died. RCS showed that HOMA-IR had a segmented effect on all-cause mortality. 3.59 was a statistically significant inflection point. When the HOMA-IR was less than 3.59, it was negatively associated with all-cause mortality [HR = 0.87,95%CI (0.78, 0.97)]. Conversely, when the HOMA-IR was greater than 3.59, it was positively associated with all-cause mortality [HR = 1.03,95%CI (1.00, 1.05)]. ROC and calibration curves indicated that HOMA-IR was a reliable predictor of survival status (area under curve = 0,812). No interactions between HOMA-IR and stratified variables were found.

Conclusion

The relationship between HOMA-IR and all-cause mortality was U-shaped in patients with CHD and hypertension. HOMA-IR was a reliable predictor of all-cause mortality in this population.
Mucosal-associated invariant T cells in infectious diseases of respiratory system: recent advancements and applications
Authors: Lin Xue , Wang Ye , He Yanqi
Published: February 2024

Mucosal-associated invariant T (MAIT) cells are an atypical subset of T lymphocytes, which have a highly conserved semi-constant αβ chain of T-cell receptor (TCR) and recognize microbe-derived vitamin B metabolites via major histocompatibility complex class I related-1 molecule (MR1). MAIT cells get activated mainly through unique TCR-dependent and TCR-independent pathways, and express multiple functional and phenotypic traits, including innate-like functionality, T helper (Th) 1 cell immunity, Th 17 cell immunity, and tissue homing. Given the functions, MAIT cells are extensively reported to play a key role in mucosal homeostasis and infectious diseases. In the current work, we review the basic characteristics of MAIT cells and their roles in mucosal homeostasis and development of respiratory infectious diseases as well as their potential therapeutic targets.
Exosome proteomes reveal glycolysis-related enzyme enrichment in primary canine mammary gland tumor compared to metastases
Authors: Kim Hui-Su , Cho Je-Yoel
Published: February 2024

Objective

Numerous evidence has highlighted the differences between primary tumors and metastases. Nonetheless, the differences in exosomal proteins derived from primary tumor and metastases remain elusive. Here, we aimed to identify differentially expressed exosomal proteins from primary canine mammary gland tumor and metastases to understand how they shape their own tumor microenvironment.

Methods

We clearly distinguished primary canine mammary gland tumors (CHMp) from metastases (CHMm) and profiled the proteins within their secreted exosomes using LC–MS/MS. Moreover, the abundance of glycolysis enzymes (GPI, LDHA) in CHMp exosome was verified with Western blotting, To broaden the scope, we extended to human colorectal cancer-derived exosomes (SW480 vs. SW620) for comparison.

Results

We identified significant differences in 87 and 65 proteins derived from CHMp and CHMm, respectively. Notably, glycolysis enzymes (GPI, LDHA, LDHB, TPI1, and ALDOA) showed specific enrichment in exosomes from the primary tumor.

Conclusion

We observed significant differences in the cellular proteome between primary tumors and metastases, and intriguingly, we identified a parallel heterogeneity the protein composition of exosomes. Specifically, we reported that glycolysis enzymes were significantly enriched in CHMp exosomes compared to CHMm exosomes. We further demonstrated that this quantitative difference in glycolysis enzymes persisted across primary and metastases, extending to human colorectal cancer-derived exosomes (SW480 vs. SW620). Our findings of the specific enrichment of glycolysis enzymes in primary tumor-derived exosomes contribute to a better understanding of tumor microenvironment modulation and heterogeneity between primary tumors and metastases.
Phosphorylation of PP2Ac by PKC is a key regulatory step in the PP2A-switch-dependent AKT dephosphorylation that leads to apoptosis
Authors: Nadel Guy , Yao Zhong , Hacohen-Lev-Ran Avital , Wainstein Ehud , Maik-Rachline Galia , Ziv Tamar , Naor Zvi , Admon Arie , Seger Rony
Published: February 2024

Background

Although GqPCR activation often leads to cell survival by activating the PI3K/AKT pathway, it was previously shown that in several cell types AKT activity is reduced and leads to JNK activation and apoptosis. The mechanism of AKT inactivation in these cells involves an IGBP1-coupled PP2Ac switch that induces the dephosphorylation and inactivation of both PI3K and AKT. However, the machinery involved in the initiation of PP2A switch is not known.

Methods

We used phospho-mass spectrometry to identify the phosphorylation site of PP2Ac, and raised specific antibodies to follow the regulation of this phosphorylation. Other phosphorylations were monitored by commercial antibodies. In addition, we used coimmunoprecipitation and proximity ligation assays to follow protein–protein interactions. Apoptosis was detected by a TUNEL assay as well as PARP1 cleavage using SDS-PAGE and Western blotting.

Results

We identified Ser24 as a phosphorylation site in PP2Ac. The phosphorylation is mediated mainly by classical PKCs (PKCα and PKCβ) but not by novel PKCs (PKCδ and PKCε). By replacing the phosphorylated residue with either unphosphorylatable or phosphomimetic residues (S24A and S24E), we found that this phosphorylation event is necessary and sufficient to mediate the PP2A switch, which ultimately induces AKT inactivation, and a robust JNK-dependent apoptosis.

Conclusion

Our results show that the PP2A switch is induced by PKC-mediated phosphorylation of Ser24-PP2Ac and that this phosphorylation leads to apoptosis upon GqPCR induction of various cells. We propose that this mechanism may provide an unexpected way to treat some cancer types or problems in the endocrine machinery.
Elevated SLC7A2 expression is associated with an abnormal neuroinflammatory response and nitrosative stress in Huntington’s disease
Authors: Gaudet Ian D. , Xu Hongyuan , Gordon Emily , Cannestro Gianna A. , Lu Michael L. , Wei Jianning
Published: February 2024

We previously identified solute carrier family 7 member 2 (SLC7A2) as one of the top upregulated genes when normal Huntingtin was deleted. SLC7A2 has a high affinity for l-arginine. Arginine is implicated in inflammatory responses, and SLC7A2 is an important regulator of innate and adaptive immunity in macrophages. Although neuroinflammation is clearly demonstrated in animal models and patients with Huntington’s disease (HD), the question of whether neuroinflammation actively participates in HD pathogenesis is a topic of ongoing research and debate. Here, we studied the role of SLC7A2 in mediating the neuroinflammatory stress response in HD cells. RNA sequencing (RNA-seq), quantitative RT-PCR and data mining of publicly available RNA-seq datasets of human patients were performed to assess the levels of SLC7A2 mRNA in different HD cellular models and patients. Biochemical studies were then conducted on cell lines and primary mouse astrocytes to investigate arginine metabolism and nitrosative stress in response to neuroinflammation. The CRISPR–Cas9 system was used to knock out SLC7A2 in STHdhQ7 and Q111 cells to investigate its role in mediating the neuroinflammatory response. Live-cell imaging was used to measure mitochondrial dynamics. Finally, exploratory studies were performed using the Enroll-HD periodic human patient dataset to analyze the effect of arginine supplements on HD progression. We found that SLC7A2 is selectively upregulated in HD cellular models and patients. HD cells exhibit an overactive response to neuroinflammatory challenges, as demonstrated by abnormally high iNOS induction and NO production, leading to increased protein nitrosylation. Depleting extracellular Arg or knocking out SLC7A2 blocked iNOS induction and NO production in STHdhQ111 cells. We further examined the functional impact of protein nitrosylation on a well-documented protein target, DRP-1, and found that more mitochondria were fragmented in challenged STHdhQ111 cells. Last, analysis of Enroll-HD datasets suggested that HD patients taking arginine supplements progressed more rapidly than others. Our data suggest a novel pathway that links arginine uptake to nitrosative stress via upregulation of SLC7A2 in the pathogenesis and progression of HD. This further implies that arginine supplements may potentially pose a greater risk to HD patients.
IL-6 from cerebrospinal fluid causes widespread pain via STAT3-mediated astrocytosis in chronic constriction injury of the infraorbital nerve
Authors: Yu Ning , Cui Huan , Jin Sixuan , Liu Penghao , Fang Yehong , Sun Fengrun , Cao Yan , Yuan Bo , Xie Yikuan , Duan Wanru , Ma Chao
Published: February 2024

Background

The spinal inflammatory signal often spreads to distant segments, accompanied by widespread pain symptom under neuropathological conditions. Multiple cytokines are released into the cerebrospinal fluid (CSF), potentially inducing the activation of an inflammatory cascade at remote segments through CSF flow. However, the detailed alteration of CSF in neuropathic pain and its specific role in widespread pain remain obscure.

Methods

A chronic constriction injury of the infraorbital nerve (CCI-ION) model was constructed, and pain-related behavior was observed on the 7th, 14th, 21st, and 28th days post surgery, in both vibrissa pads and hind paws. CSF from CCI-ION rats was transplanted to naïve rats through intracisternal injection, and thermal and mechanical allodynia were measured in hind paws. The alteration of inflammatory cytokines in CCI-ION’s CSF was detected using an antibody array and bioinformatic analysis. Pharmacological intervention targeting the changed cytokine in the CSF and downstream signaling was performed to evaluate its role in widespread pain.

Results

CCI-ION induced local pain in vibrissa pads together with widespread pain in hind paws. CCI-ION’s CSF transplantation, compared with sham CSF, contributed to vibrissa pad pain and hind paw pain in recipient rats. Among the measured cytokines, interleukin-6 (IL-6) and leptin were increased in CCI-ION’s CSF, while interleukin-13 (IL-13) was significantly reduced. Furthermore, the concentration of CSF IL-6 was correlated with nerve injury extent, which gated the occurrence of widespread pain. Both astrocytes and microglia were increased in remote segments of the CCI-ION model, while the inhibition of astrocytes in remote segments, but not microglia, significantly alleviated widespread pain. Mechanically, astroglial signal transducer and activator of transcription 3 (STAT3) in remote segments were activated by CSF IL-6, the inhibition of which significantly mitigated widespread pain in CCI-ION.

Conclusion

IL-6 was induced in the CSF of the CCI-ION model, triggering widespread pain via activating astrocyte STAT3 signal in remote segments. Therapies targeting IL-6/STAT3 signaling might serve as a promising strategy for the widespread pain symptom under neuropathological conditions.

Graphical abstract
Inhibition of MMP8 effectively alleviates manic-like behavior and reduces neuroinflammation by modulating astrocytic CEBPD
Authors: Wang Tzu-Yun , Weng Eddie Feng-Ju , Hsu Yun-Chen , Shiu Lu-Ping , Huang Teng-Wei , Wu Hsuan-Cheng , Hong Jau-Shyong , Wang Shao-Ming
Published: February 2024

There is an intrinsic relationship between psychiatric disorders and neuroinflammation, including bipolar disorder. Ouabain, an inhibitor of Na+/K+-ATPase, has been implicated in the mouse model with manic-like behavior. However, the molecular mechanisms linking neuroinflammation and manic-like behavior require further investigation. CCAAT/Enhancer-Binding Protein Delta (CEBPD) is an inflammatory transcription factor that contributes to neurological disease progression. In this study, we demonstrated that the expression of CEBPD in astrocytes was increased in ouabain-treated mice. Furthermore, we observed an increase in the expression and transcript levels of CEBPD in human primary astrocytes following ouabain treatment. Transcriptome analysis revealed high MMP8 expression in human primary astrocytes following CEBPD overexpression and ouabain treatment. We confirmed that MMP8 is a CEBPD-regulated gene that mediates ouabain-induced neuroinflammation. In our animal model, treatment of ouabain-injected mice with M8I (an inhibitor of MMP8) resulted in the inhibition of manic-like behavior compared to ouabain-injected mice that were not treated with M8I. Additionally, the reduction in the activation of astrocytes and microglia was observed, particularly in the hippocampal CA1 region. Excessive reactive oxygen species formation was observed in ouabain-injected mice, and treating these mice with M8I resulted in the reduction of oxidative stress, as indicated by nitrotyrosine staining. These findings suggest that MMP8 inhibitors may serve as therapeutic agents in mitigating manic symptoms in bipolar disorder.
An integrated theory based-educational intervention to change intention to have a child: study protocol of a cluster randomized controlled trial
Authors: Moridi Maryam , Damghanian Maryam , Keshaverz Sedigheh
Published: February 2024

Background

In high- and low-income countries, declining birth rates have become a global concern. Couples do not have enough information about the complications of delaying and reducing childbearing and this leads them to make inappropriate decisions. Therefore, this study aims to evaluate whether an educational program based on integrating the Theory of Planned Behavior (TPB) and the Trans-Theoretical Model (TTM) affects child-free couples’ intention to have children and minimizes the consequences of this decline.

Methods

Thirty couples (intervention, n = 15; control, n = 15) will be enrolled in this cluster randomized controlled trial. After collecting baseline data and separating participants in the pre-contemplation and contemplation stages based on the TTM, the samples were randomly assigned to the intervention and control groups. The intervention group will receive 60-min training based on TPB components for 4 weeks. The first follow-up assessment was performed immediately after the intervention and the final assessment 6 months later. For all 3 time assessments, three questionnaires will be used: The knowledge questionnaire, the TTM, and the TPB questionnaire. The most important consequences are changes in knowledge, attitudes, subjective norms, perceived behavioral control, and stages of intentions to have children.

Discussion

Decision-makers will use the results of this study as a basis to design appropriate, transparent, and useful policies and interventions to improve or stop the decline of the fertility rate at the national level. Also, this study will help young couples who wish to have a child in their lifetime by providing relevant information so that they do not miss this opportunity and face the consequences of delaying having a child.

Trial registrationThis study was approved by the Iranian Registry of Clinical Trials (IRCT), Number: IRCT20220618055210N2, Date of registration: 2023-10-03