bluuebunny/crossref_metadata_2025 huggingface dataset:
Methodology for determination of seismic force modification factors in Canada: Performance-based unified procedure
Authors: Fazileh Farrokh , Fathi-Fazl Reza , Dolati Abouzar , Ventura Carlos E , Saatcioglu Murat , Lau David , Yang TY , Sadeghian Vahid , Erochko Jeffrey
Published: January 2023

The National Building Code of Canada (NBC) employs seismic force modification factors (i.e. ductility-related factor, Rd, and an overstrength-related factor, Ro) for different Seismic Force Resisting Systems (SFRSs), which, since 2005, are largely based on engineering judgment and qualitative comparisons of seismic response characteristics of different SFRSs. Currently, there is no unified procedure in Canada for systematically quantifying these values, which has potentially led to perceived inconsistent levels of performance between buildings built with different SFRSs. While some research has been carried out in Canada to quantitatively evaluate the seismic response of different SFRSs using the FEMA P695 methodology with some modifications, inconsistencies exist among different research works. Moreover, the number of archetypes developed in these studies was limited, due to the computationally laborious incremental dynamic analysis (IDA) step in FEMA P695. Therefore, there is a need for a consistent and efficient methodology for structural performance assessment of different SFRSs in Canada. The proposed performance-based unified (PBU) procedure is to systematically quantify Rd and Ro factors for different SFRSs in the NBC. The PBU procedure is designed to be a performance-based approach (vs the risk-based approach of FEMA P695). In addition, our procedure is devised to optimize the number of archetypes through a two-level screening procedure using a nonlinear pushover and time history analyses before running the IDA. To validate the PBU procedure, we developed 21 different concrete moment frame archetypes covering various key parameters. The results verify the efficiency of the screening feature of the PBU procedure by a significant reduction in the number of archetypes requiring IDA.
A rheology and processing study on controlling material and process defects in polymer melt extrusion film casting using polymer blends
Authors: Rokade Dhammaraj , Patil Prashant , Nandimath Sheetal , Pol Harshawardhan
Published: January 2023

The primary objective of this research paper is to control the material and process defects in polymer melt extrusion film casting (EFC) process for linear chain architecture polyethylene (PE) resins through polymer blending methodology. Extrusion film casting is a well-known industrially important manufacturing process that is used to manufacture thousands of tons of polymer/plastic films/sheets and coated products. In this research, the necking defect in an EFC process has been studied experimentally for a linear low density polyethylene (LLDPE) resin and attempts have been made to control its necking by blending in a long chain branched (LCB) low density polyethylene (LDPE) resin. The blending methodology is based on the understanding that a LDPE resin displays enhanced resistance to necking as compared to the LLDPE resin. It is found that added LDPE resin enhances necking resistance for the primary LLDPE resin. Further, as the LDPE concentration increases in the blend formulation, the necking is further reduced as compared to pure LLDPE. Analogous to past studies on EFC of linear and long chain branched architecture containing PEs, it is observed that as the LDPE is increased in the blend formulations, the formulations displayed enhanced melt elasticity and extensional strain hardening in rheological studies. It is concluded from this study that polyethylene resins having linear chain architecture can be made amenable to enhanced resistance to necking using appropriate amount of a long chain branched resins. Finally, process defects such as the draw resonance onset could be shifted to higher draw ratios as the LDPE level is increased in the LLDPE-LDPE blend formulation.
Hereditary platelet disorders associated with germ line variants in RUNX1, ETV6, and ANKRD26
Authors: Homan Claire C. , Scott Hamish S. , Brown Anna L.
Published: January 2023

Hereditary platelet disorders (HPDs) are a group of blood disorders with variable severity and clinical impact. Although phenotypically there is much overlap, known genetic causes are many, prompting the curation of multigene panels for clinical use, which are being deployed in increasingly large-scale populations to uncover missing heritability more efficiently. For some of these disorders, in particular RUNX1, ETV6, and ANKRD26, pathogenic germ line variants in these genes also come with a risk of developing hematological malignancy (HM). Although they may initially present as similarly mild-moderate thrombocytopenia, each of these 3 disorders have distinct penetrance of HM and a different range of somatic alterations associated with malignancy development. As our ability to diagnose HPDs has improved, we are now faced with the challenges of integrating these advances into routine clinical practice for patients and how to optimize management and surveillance of patients and carriers who have not developed malignancy. The volume of genetic information now being generated has created new challenges in how to accurately assess and report identified variants. The answers to all these questions involve international initiatives on rare diseases to better understand the biology of these disorders and design appropriate models and therapies for preclinical testing and clinical trials. Partnered with this are continued technological developments, including the rapid sharing of genetic variant information and automated integration with variant classification relevant data, such as high-throughput functional data. Collective progress in this area will drive timely diagnosis and, in time, leukemia preventive therapeutic interventions.
Pulmonary renal syndrome: a clinical review
Authors: Boyle Niamh , O'Callaghan Marissa , Ataya Ali , Gupta Nishant , Keane Michael P. , Murphy David J. , McCarthy Cormac
Published: January 2023

The term “pulmonary renal syndrome” describes a clinical syndrome which is characterised by the presence of both diffuse alveolar haemorrhage and glomerulonephritis. It encompasses a group of diseases with distinctive clinical and radiological manifestations, as well as different pathophysiological processes. The most common diseases implicated are anti-neutrophil cytoplasm antibodies (ANCA)-positive small vessel vasculitis and anti-glomerular basement membrane (anti-GBM) disease. Prompt recognition is required as respiratory failure and end-stage renal failure can rapidly occur. Treatment includes a combination of glucocorticoids, immunosuppression, plasmapheresis and supportive measures. The use of targeted treatments has significantly reduced mortality. Thus, an understanding of pulmonary renal syndrome is essential for the respiratory physician.
Migraine attacks are of peripheral origin: the debate goes on
Authors: Do Thien Phu , Hougaard Anders , Dussor Greg , Brennan K. C. , Amin Faisal Mohammad
Published: January 2023

Background

Despite the pervasiveness of migraine, the underlying pathophysiological mechanisms initiating migraine attacks are far from well understood and are matter of scientific debate.

Objective

In this narrative review, we discuss key evidence for that suggest a peripheral origin or central origin and provide directions for future studies that may provide further clarification.

Discussion

Migraine pathogenesis is considered to involve the trigeminovascular system, a term that encompasses the trigeminal nerve and its axonal projections to the intracranial blood vessels. Beyond any doubt both peripheral and central mechanisms are involved in migraine pathogenesis, but an unresolved question is the how the initial activation occurs in a migraine attack. Evidence favoring a peripheral origin of migraine attacks, i.e., initial events occur outside of the blood–brain barrier, include the importance of sensitization of perivascular sensory afferents early on in a migraine attack. Evidence favoring a central origin include the occurrence of prodromal symptoms, migraine aura, and activation of structures within the central nervous system early in and during a migraine attack.

Conclusions

Both peripheral and central mechanisms are likely involved in a migraine attack, e.g., peripheral nociceptive input is necessary for pain transmission and cortical activity is necessary for pain perception. Yet, the debate of whether migraine attacks are initiated a peripheral or central site remains unresolved. The increased focus on prodromal symptoms and on the development of a human model of migraine aura will possibly provide key arguments needed to answer this question in the near future. Until then, we cannot draw firm conclusions and the debate goes on.

Video link

Video recording of the debate held at the 1st International Conference on Advances in Migraine Sciences (ICAMS 2022, Copenhagen, Denmark) is available at: https://www.youtube.com/watch?v=NC0nlcKohz0.

Graphical Abstract
ROX index versus HACOR scale in predicting success and failure of high-flow nasal cannula in the emergency department for patients with acute hypoxemic respiratory failure: a prospective observational study
Authors: Praphruetkit Nattakarn , Boonchana Natyada , Monsomboon Apichaya , Ruangsomboon Onlak
Published: January 2023

Background

High-flow nasal cannula has been a promising initial respiratory support measure for patients with acute hypoxemic respiratory failure (AHRF) in the emergency department (ED). However, delayed detection of HFNC failure is associated with increased mortality. The ROX index is a tool that can help predict HFNC success. Nonetheless, its utility in ED patients is limited, and no studies have compared it with the HACOR scale, another tool that may be as accurate in predicting HFNC failure. Therefore, we aimed to compare the prognostic utility of the ROX index and the HACOR scale in emergency AHRF patients.

Methods

This prospective observational study was conducted at the ED of Siriraj Hospital, Thailand, between August 2018 and February 2020. Adult patients with AHRF requiring HFNC in the ED were included. The ROX index and the HACOR scale were measured at 1, 2, and 6 h after HFNC initiation. The primary outcome was HFNC success, defined as no intolerance or escalation towards mechanical ventilation or non-invasive ventilation within 48 h.

Results

A total of 75 patients were enrolled; 52 (69.3%) had a successful treatment. The ROX index was higher in the success group, while the HACOR scale was lower at all timepoints. The ROX index yielded generally higher discrimination capacity based on the area under the receiver operating characteristic curve (AUROC) than the HACOR scale [AUROC at 1, 2, and 6 h = 0.815, 0.784, 0.853 for ROX in predicting HFNC success and 0.733, 0.690, and 0.764 for HACOR in predicting HFNC failure]. The ROX index measured at 6 h at the cut-point of 4.88 had 92.98% sensitivity, 61.11% specificity, 88.33% positive predictive value, and 73.33% negative predictive value with a diagnostic accuracy of 85.33%.

Conclusion

The ROX index had superior prognostic utility in predicting HFNC outcome (success/failure) compared to the HACOR scale in patients with AHRF in the ED setting. Moreover, it is less complex and more efficient to be employed at bedside. Therefore, the ROX index is a more appropriate tool to guide further management and potential escalation therapy for AHRF patients with HFNC therapy initiated in the ED.
Melamine in the environment: a critical review of available information
Authors: Lütjens Laura H. , Pawlowski Sascha , Silvani Maurizio , Blumenstein Uwe , Richter Ingo
Published: January 2023

Large numbers of chemicals and products thereof are used in our daily routine to ensure a good quality of life. Substances may even serve as raw materials to produce daily life articles including electronic hardware, green houses, cars etc. Melamine is used for a great variety of products, such as wood panels, paints, coatings, foam seating’s and mattresses (as flame retardant), automotive brake tubes and hose. Based on the latest discussions, melamine has been concluded in the European Union to be classified as “carcinogenic to humans” (Carc. 2, H351) and “may cause damage to organs (urinary tract) through prolonged or repeated exposure” (STOT RE 2, H737). In addition, there is a self-classification of the European industry as suspect Repr. CAT2. Furthermore, the substance is considered a potential groundwater contaminant, due to a low log octanol carbon coefficient (Koc). However, the underlying data require further evaluation. Therefore, a review of available information related to the presence of melamine (M) and cyromazine (CM, of which M is a transformation product) in surface, ground and drinking water was conducted and the data were critically analysed for plausibility. Available monitoring data are scarce and investigated for the Netherlands and Germany mainly. Measurements in the catchment area of the river Rhine and Maas revealed, that both substances (M, CM) were not ubiquitously found in surface, ground and drinking water in these countries. All in all, it can be concluded that the available monitoring data are considered as conclusive, and thus requiring further investigation before a clear relationship between emission and occurrence of melamine in the environment can be drawn.
Evaluation and limitations of different approaches among COVID-19 fatal cases using whole-exome sequencing data
Authors: Forgacova Natalia , Holesova Zuzana , Hekel Rastislav , Sedlackova Tatiana , Pos Zuzana , Krivosikova Lucia , Janega Pavol , Kuracinova Kristina Mikus , Babal Pavel , Radvak Peter , Radvanszky Jan , Gazdarica Juraj , Budis Jaroslav , Szemes Tomas
Published: January 2023

Background

COVID-19 caused by the SARS-CoV-2 infection may result in various disease symptoms and severity, ranging from asymptomatic, through mildly symptomatic, up to very severe and even fatal cases. Although environmental, clinical, and social factors play important roles in both susceptibility to the SARS-CoV-2 infection and progress of COVID-19 disease, it is becoming evident that both pathogen and host genetic factors are important too. In this study, we report findings from whole-exome sequencing (WES) of 27 individuals who died due to COVID-19, especially focusing on frequencies of DNA variants in genes previously associated with the SARS-CoV-2 infection and the severity of COVID-19.

Results

We selected the risk DNA variants/alleles or target genes using four different approaches: 1) aggregated GWAS results from the GWAS Catalog; 2) selected publications from PubMed; 3) the aggregated results of the Host Genetics Initiative database; and 4) a commercial DNA variant annotation/interpretation tool providing its own knowledgebase. We divided these variants/genes into those reported to influence the susceptibility to the SARS-CoV-2 infection and those influencing the severity of COVID-19. Based on the above, we compared the frequencies of alleles found in the fatal COVID-19 cases to the frequencies identified in two population control datasets (non-Finnish European population from the gnomAD database and genomic frequencies specific for the Slovak population from our own database). When compared to both control population datasets, our analyses indicated a trend of higher frequencies of severe COVID-19 associated risk alleles among fatal COVID-19 cases. This trend reached statistical significance specifically when using the HGI-derived variant list. We also analysed other approaches to WES data evaluation, demonstrating its utility as well as limitations.

Conclusions

Although our results proved the likely involvement of host genetic factors pointed out by previous studies looking into severity of COVID-19 disease, careful considerations of the molecular-testing strategies and the evaluated genomic positions may have a strong impact on the utility of genomic testing.
Mobile APP-assisted family physician program for improving blood pressure outcome in hypertensive patients
Authors: Xing Fang , Guo Yijia , Xia Nan , Zhang Suolei , Yin Jinfeng , Qin Liyi , Zhu Chendi , Gao Qing , Jia Junnan , Zhao Yuesong , Qi Yousheng , Li Weimin
Published: January 2023

Background

This study was aimed to examine the effectiveness of App-assisted self-care in a Beijing community based on intelligent family physician-optimised collaborative model (IFOCM) program. 

Methods

We conducted a survey of 12,050 hypertensive patients between Jan 2014 and Dec 2021. Generalized linear model was used to analyze the covariates that associated with blood pressure (BP) control. Decision tree and random forest algorithm was used to extract the important factors of BP outcome.

Results

The study included 5937 patients, mean age 66.2 ± 10.8, with hypertension in the baseline; 3108(52.4) were female. The community management resulted in mean systolic BP and diastolic BP reductions of 4.6 mmHg and 3.8 mmHg at follow-up. There were 3661 (61.6%) hypertension patients with BP control, increasing from 55.0% in 2014 to 75.0% in 2021. After adjusted for covariates, antihypertensive medication adherence, diabetes, and APP-assisted self-care were common predictors associated with BP control in GLM model and machine learning algorithm.

Conclusion

Community management based on IFOCM program significantly improved BP control in hypertensive patients. APP-assisted self-care would be beneficial for the management of chronic disease.
Peripheral blood lymphocyte subsets in children with nephrotic syndrome: a retrospective analysis
Authors: Deng Yan , Ou Ying-ying , Mo Cui-Ju , Huang Li , Qin Xue , Li Shan
Published: January 2023

Background

Nephrotic syndrome (NS) in children is widely believed to be associated with severe changes in the immune system. Based on lymphocyte subset analysis, we examined the pathogenesis of immune deficiencies in children with NS with varying steroid sensitivity.

Methods

Our study utilized flow cytometry to retrospectively analyze the ratios of lymphocyte subsets in 204 children with nephrotic syndrome and 19 healthy children.

Results

Compared with healthy children, the ratio of CD4 + /CD8 + in onset and remission was decreased in SRNS group (p < 0.05), and CD19 + B lymphocytes were increased in onset (p < 0.05). Compared with onset, the proportion of CD19 + B lymphocytes decreased in SRNS, while the proportion of CD19 + B lymphocytes increased in SDNS, p < (0.01). The ratio of CD8 + T/CD19 + B in onset in SDNS group was significantly higher than that in SSNS and SRNS groups (p < 0.01) and healthy control group (p < 0.05). Compared with onset, the ratio of CD8 + T/CD19 + B in SDNS group decreased significantly (p < 0.01), while the ratio of CD8 + T/CD19 + B in SRNS group increased significantly (p < 0.01). The proportion of CD56 + CD16 + NK cells was significantly reduced in children with INS (p < 0.01).

Conclusion

CD8 + T lymphocytes may be involved in the mechanism of lymphocyte subsets disorder during onset of SDNS, while CD19 + B lymphocytes may be involved in the mechanism of lymphocyte subsets disorder during relapse of SDNS. The CD8 + T/CD19 + B ratio may predict the degree of frequent recurrence. There is a certain degree of lymphoid subsets disorder in children with NS.
Awareness and knowledge of glaucoma among visitors of main public hospitals in Damascus, Syria: a cross-sectional study
Authors: Soqia Jameel , Ataya Jamal , Alhalabi Rawan , Alhomsi Rawan , Hamwy Romeo , Mardini Khaled , Hamzeh Ammar
Published: January 2023

Background

The main way to prevent blindness from Glaucoma is by early detection and diagnosis; and to do so the awareness must be raised among people where Glaucoma is defined as an acquired chronic optic neuropathy characterized by optic disk cupping and visual field loss. Lack of knowledge about this disease is one of the most important reasons that made it develop to advanced stages. Based on that, we conducted scientific research to assess peoples’ awareness and knowledge about Glaucoma.

After reviewing the literature, it was found that this study is the first in Syria.

Methods

We conducted a cross-sectional study in May 2022. The study included participants, who are above 20 years old, from visitors of Al-Mouwasat University Hospital in Damascus, Syria. During one week, Data was gathered according to the questionnaire, which was presented through face-to-face interviews with participants. We have allocated one point (1) to each question. Three levels of knowledge were adopted, namely; weak level from (0) to (3), average level from (4) to (7) and good level from (8) to (11). Associations between participants' demographic and other details were tested using Chi-square test and other tests, and a p-value of < 0.05 was considered significant.

Results

A total of 500 participants were interviewed. For awareness of Glaucoma, 33.6% of the participants (n = 168) had heard of Glaucoma, and 66.4% hadn’t (n = 332). Mean test results for the knowledge of Glaucoma was 1.62 out of 11, and only 8% of participants (n = 40) had a good knowledge of Glaucoma. Education Level, governorate, and department of hospital that the patient came for significantly affected the knowledge of Glaucoma. Moreover, hospital, Ophthalmologists' Clinics, and health staff (M = 5.45) were the better Resource for information than family, relatives, and friends (M = 3.16). Finally, social media and the Internet group had the lowest mean test results (M = 1.23). These test results were significant, with a p-value < 0.001.

Conclusion

The percentage of knowledge and awareness was significantly low. Organized community awareness methods must disseminate more ability to increase the general public's understanding to avoid injury and late diagnosis of Glaucoma.
Population health trends and disease profile in Somalia 1990–2019, and projection to 2030: will the country achieve sustainable development goals 2 and 3?
Authors: Morrison Joana , Malik Sk Md Mamunur Rahman
Published: January 2023

Objectives

This study aims to evaluate whether Somalia will reach Sustainable Development Goals 2 and 3 by 2030 and what the country requires to advance closer to these objectives.

Setting: Somalia.

Participants

We carried out analyses of secondary data obtained from the following open-access databases: Global Burden of Disease 2019 study; United Nations (UN) Department of Economic and Social Affairs Population Division; World Bank World Development Indicators; United Nations Children’s Fund (UNICEF); UNICEF/World Health Organisation (WHO)/World Bank Joint Child Malnutrition Estimates; and UN Interagency Group for Child Mortality Estimation (UN IGME), disaggregated by sex.

Primary outcome measures: stillbirth, neonatal, infant, under-five, maternal and child mortality; under-five malnutrition; life expectancy; health-adjusted life expectancy; age-standardised all-cause mortality; age-standardised cause-specific mortality for the leading causes of death; disability-adjusted life years. Secondary outcome measures: vitamin A coverage; stunting, overweight in children under 5; top risk factors contributing to cause-specific mortality.

Results

life expectancy in Somalia will increase to 65.42 years (95% UI 62.30–68.54) for females and 58.54 years (95% UI 54.89–62.19) for males in 2030. Stunting will continue to decline to 25.2% (90% UI 13.9–39.5%), and the under-five mortality rate will drop to 85.9 per 1000 live births (90% UI 22.0–228.1 per 1000 live births) for females and 96.4 per 1000 live births (90% UI 24.8–255.3 per 1000 live births) for males in 2030. This study’s analyses predict that the maternal mortality ratio in Somalia will decline to 696.42 deaths per 100,000 live births in 2030.

Conclusions

there has been progress towards SDG targets in Somalia since 1990. To achieve these, Somalia requires greater health improvements than observed between 1990 and 2019.
Self- and surrogate-seeking of information about mental health and illness in Germany
Authors: Freytag Anna , Baumann Eva , Angermeyer Matthias , Schomerus Georg
Published: January 2023

Background

Seeking information on mental health issues – both for oneself and on behalf of others (so-called surrogate-seeking) – is a critical early step in dealing with mental illness and known to impede stigmatizing attitudes and foster help-seeking. Yet, knowledge about mental health tends to be insufficient worldwide. Therefore, it is necessary to better understand the search for mental health information and examine the factors that are positively associated with information-seeking.

Method

In a face-to-face survey in Germany (N = 1,522), we investigated the factors related to mental health information-seeking. The data was analyzed by means of a logistic regression model, in which we distinguished those searching information for themselves from so-called surrogate seekers, i.e., people who seek information on behalf of someone else.

Results

Twenty-six percent of German adults in our sample have already searched for information on mental health, with the majority already having searched for information for others (73% of all seekers). Our findings indicate that individuals’ proximity to people with mental health issues, including their own mental health treatment experience (Cramer’s V = .429, p < .001), education (Cramer’s V = .184, p < .001), and desire for social distance from the affected people (F [1, 1516] = 73.580, p < .001, η2 = .046), play an important role in mental health information-seeking. The patterns of sociodemographic and proximity factors hereby differ between self-seekers and surrogate-seekers.

Conclusions

Our study provides insights into the public’s mental health information orientation. The findings may particularly guide strategies to improve mental health awareness and fill knowledge gaps in supporting informed decision-making and reducing stigma. Surrogate seekers appear to be an important and distinctive target group for mental health information provision. Depending on whether one wants to promote surrogate- or self-seeking seekers, different target groups and determinants should be addressed.
The association of meal-specific food-based dietary inflammatory index with cardiovascular risk factors and inflammation in a sample of Iranian adults
Authors: Mirrafiei Amin , Ansari Shakila , Jayedi Ahmad , Lesani Azadeh , Djafarian Kurosh , Shab-Bidar Sakineh
Published: January 2023

Background

This study aimed to evaluate the association of meals-specific food-based dietary inflammatory index (FDII), with cardiovascular (CVD) risk factors and inflammation among Iranian adults.

Methods

In this cross-sectional study, we recruited 816 participants living in Tehran via two-staged cluster sampling. Three non-consecutive 24-h dietary recalls (two working days and one day off) were obtained from individuals to specify the main meals and meal-specific FDIIs. Anthropometric measures were done. Insulin and high-sensitivity c-reactive protein (hs-CRP) were measured. Multiple linear regressions were used to investigate the association of FDII with Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), hs-CRP, Triglyceride Glucose Index (TyG), and Lipid Accumulation Product Index (LAP).

Results

The range of FDIIs for breakfast, lunch, and dinner were (-2.47,1.98), (-2.66,3.23) and (-4.09,3.13) in order, and the mean age was 42.2 ± 10.5 years. We found that there was no significant association between FDII and hs-CRP level in the three meals (β = -0.003; 95% CI: -0.030, 0.025 for breakfast,β = -0.020; 95% CI: -0.041, 0.001 for lunch, and β = 0.006; 95% CI: -0.016, 0.028 for dinner) after adjusting for age, sex, education, occupation, maritage, physical activity, smoking, morningness-eveningness score, energy, body mass index, and other FDIIs. Also, we found no significant association between breakfast, lunch, and dinner-specific FDII and HOMA-IR (β = -0.368, -0.223, 0.122), TyG index (β = -0.009, 0.060, -0.057) and LAP (β = 2.320, -0.278, -0.297).

Conclusions

We found no associations between meal-based FDII scores and CVD and inflammation. Further research of prospective nature is needed to confirm these findings.
α-NETA down-regulates CMKLR1 mRNA expression in ileum and prevents body weight gains collaborating with ERK inhibitor PD98059 in turn to alleviate hepatic steatosis in HFD-induced obese mice but no impact on ileal mucosal integrity and steatohepatitis progression
Authors: Zheng Canbin , Zheng Yongping , Chen Xi , Zhong Xianyang , Zheng Xiaobin , Yang Shuhui , Zheng Zihui
Published: January 2023

Background

Studies on chemerin/chemokine-like receptor-1 have mainly focused on adipose and liver with the intestinal tissues largely overlooked. In this study conducted on obese mice, we have explored: 1) CMKLR1 expression in the ileums; 2) CMKLR1 inhibitor α-NETA on body weight and intestinal mucosa integrity hence the impact on hepatic steatosis and pathway involved.

Methods

Nineteen male C57BL/6 mice were randomly divided into five groups: normal diet group (ND), high-fat diet group (HFD), HFD + α-NETA group (NETA), HFD + PD98059 group (PD) and HFD + α-NETA + PD98059 group (NETA + PD). Mice were fed either with a chow diet or HFD for 12 weeks. At 12th week, mice of ND were put on the diet as before; mice of NETA received daily treatments of α-NETA (30 mg/kg) via gavage; mice of PD received daily treatment of PD98059 via tail vein injection; mice of NETA + PD received daily treatment of α-NETA + PD98059, all for another 4 weeks. At the time intervention ended, mice were sacrificed. The body weight, the liver pathologies were assessed. Ileal CMKLR1 mRNA was evaluated by rtPCR; ZO-1, ERK1/2 protein expression of ileal tissues by western blotting; liver TNF-α and serum endotoxin by Elisa.

Results

More weight gains in mice of HFD than ND (37.90 ± 3.00 g) vs (24.47 ± 0.50 g), P = 0.002; α-NETA reduced the body weight (33.22 ± 1.90 g) vs (37.90 ± 3.00 g), P = 0.033; and further reduced by NETA + PD98059: (31.20 ± 1.74 g) vs (37.30 ± 4.05 g), P = 0.032. CMKLR1 mRNA expression was up-regulated in ileum in group HFD compared with ND and down-regulated by α-NETA. Steatosis was only alleviated in group PD + NETA with less weight gain. No impact of α-NETA on ileal ZO-1 or pERK with western blotting, and no endotoxin level changes were detected. TNF-α was higher in group HFD than in group ND, while no significant difference between other groups.

Conclusions

CMKLR1 mRNA was up-regulated in the ileum of obese mice and down-regulated by α-NETA along with a body weight control collaborating with ERK inhibitor PD98059. Steatosis was alleviated in a weight dependent way. α-NETA has no influence on intestinal mucosal integrity and no impact on steatohepatitis progression.
How do medical students learn in an online community diagnostics program?
Authors: Haruta Junji , Ando Takayuki , Fujishima Seitaro
Published: January 2023

Background

The need to engage medical students in understanding the social and environmental determinants of health in disparate communities is increasing. However, previous reviews have noted the limited community diagnosis programs and program evaluation. Given the feasibility of the programs, it is expected to be widely available online. Therefore, this study used a realist approach to identify learning patterns through an online community diagnosis program, namely context (C), mechanism (M), and outcomes (O) patterns.

Methods

A 2-week general medicine clinical practice program was conducted for 4th- and 5th-year medical students at a medical university in Japan. The program included a one-hour zoom-based lecture, feedback for students on their presentations on community diagnosis, and a structural report on community diagnosis. We developed the program based on variation theory, which views discernment and variation in situations having time, space, and social dimensions as core learning. The students' reflections on their learning through the program were thematically analyzed through CMO perspectives. The realist approach used in the online diagnosis program evaluation allows us to explore, test, and refine what mechanisms work under what conditions (context) and with what interventions (including opportunities and resources), from which we can describe iteratively explainable results.

Results

First, the medical students, who spent most of their time in the limited residential areas they lived in, discovered the characteristics of their own community by discovery learning and comparison among peers. Second, they increased their intrinsic interest in the community by discerning specific issues in their familiar community through community diagnosis. Third, they valued community diagnosis by identifying relationships between local data on health issues under their learning responsibility. Fourth, they become more flexible in their thinking and created new knowledge that would fit the local community, and their reflection on themselves was encouraged.

Conclusion

In this online community diagnosis program, medical students learned about the community through four types of learning patterns. Medical students may develop an understanding of community with interest using variation theory as a program development perspective and cognitive flexibility theory surrounding the essential ambiguity and abstraction of community.
Still in the shadows: a national study of acute mental health unit location across New Zealand hospitals
Authors: Lian Anne , Carr Gawen , Peterson Debbie , Jenkin Gabrielle , Lockett Helen , Every-Palmer Susanna , Cunningham Ruth
Published: January 2023

Background

This study aimed to explore the location of acute mental health inpatient units in general hospitals by mapping their location relative to hospital facilities and community facilities and to compare their proximity to hospital facilities with that of general medical acute units.

Methods

We obtained Google maps and hospital site maps for all New Zealand public hospitals. Geographic data were analysed and mental health units’ locations in relation to hospital facilities and public amenities were mapped. Radar plots were constructed comparing acute medical and mental health units’ locations in relation to hospital facilities.

Results

Twenty-two mental health units were identified. They were located predominantly at the periphery of hospital campuses, but also at a distance from community facilities. Compared to acute medical units, mental health units were almost universally located further from shared hospital facilities – with distances approximately three times further to reach the main hospital entrance (2.7 times distance), the nearest public café (3.4 times), the emergency department (2.4 times), and medical imaging (3.3 times).

Conclusion

Despite the reforms of the 20th Century, mental health units still appear to occupy a liminal space; neither fully integrated into the hospital, nor part of the community. The findings warrant further investigation to understand the impact of these structural factors on parity of health care provision between mental and physical health care and the ability of mental health care services to support recovery.
Nitrate containing vegetables and dietary nitrate and nonalcoholic fatty liver disease: a case control study
Authors: Mirmiran Parvin , Teymoori Farshad , Farhadnejad Hossein , Mokhtari Ebrahim , Salehi-Sahlabadi Ammar
Published: January 2023

Background

Vegetables is the main sources of dietary nitrate. Studies suggested the potential link between nitrate content of vegetables and reduce the risk of chronic diseases. We aimed to assess the association between nitrate-containing vegetables (NCVs) with odds of nonalcoholic fatty liver diseases (NAFLD) in Iranian adults.

Method

This case-control study was performed on a total of 225 newly diagnosed NAFLD cases and 450 controls aged 20–60 years. Individuals’ dietary intakes were determined using a valid and reliable food frequency questionnaire.

Results

The mean ± SD age and BMI of participants were 38.1 ± 8.8 years and 26.8 ± 4.3 kg/m2, respectively. In the fully adjusted model, the odds of NAFLD were decreased across tertiles of total NCVs [(adjusted OR: 0.20, 95%CI: 0.10–0.40), (Ptrend <  0.001)] and low-nitrate vegetables [(adjusted OR: 0.22, 95%CI: 0.11–0.48), (Ptrend <  0.001)]. Our results showed that each one SD increments in nitrate content of vegetables (adjusted OR: 0.73, 95%CI: 0.55–0.97) and nitrate content of fruits (adjusted OR: 0.59, 95%CI: 0.36–0.97) was associated with reduced odds of NAFLD (P <  0.05). However, there was a positive association between each one SD increments in nitrate content of dairy products and meats and processed meats with odds of NAFLD (adjusted OR: 1.34, 95%CI: 1.03–1.74), (P <  0.05).

Conclusion

Our finding suggested that a higher intake of vegetable nitrate may be related to a decrease the odds of NAFLD.
The effect of recombinant versus plasma-derived von Willebrand factor on prolonged PFA closure times in ECMO patients with acquired von Willebrand syndrome – an observational study
Authors: Büchsel Martin , Geisen Ulrich , Beckenkamp Clara , Wengenmayer Tobias , Zieger Barbara , Westermann Dirk , Siegel Patrick M.
Published: January 2023

Background

Extracorporeal membrane oxygenation (ECMO) is applied in patients with respiratory or cardiopulmonary failure, but bleeding is a frequent complication contributing to the high mortality rates in this patient collective. A major factor predisposing patients to bleeding events is an acquired von Willebrand syndrome (aVWS). So far, specific treatment options for this phenomenon are lacking. In hereditary von Willebrand disease (VWD), treatment with recombinant or plasma-derived von Willebrand factor (rVWF or pVWF) is common practice. Closure time measured by the Platelet Function Analyser-200 (PFA-200) is an established assay to detect defects in primary hemostasis and the method is useful to monitor the effect of hemostatic therapy. The aim of this study was to assess the effect of recombinant (rVWF) vs. plasma-derived von Willebrand factor (pVWF) on closure times measured by PFA in blood obtained from ECMO patients with aVWS.

Methods

Blood was sampled from thirteen patients receiving extracorporeal membrane oxygenation and three patients with hereditary VWD. Diagnosis of aVWS was made by conventional coagulation parameters and by multimeric structure analysis. PFA analysis of blood spiked with rVWF or pVWF was performed.

Results

Thirteen patients receiving ECMO were recruited. Ten patients survived and three patients suffered major bleeding complications. PFA closure times in ECMO patients with aVWS spiked with rVWF were significantly shorter at all concentrations than with pVWF (e.g., rVWF vs. pVWF: 1 U/ml: 150.4 ± 21.7 s vs. 263.8 ± 11.7 s; 4 U/ml: 97.8 ± 9.8 s vs. 195.8 ± 15.4 s, p<0.001). PFA closure times were also significantly shorter in three patients with hereditary VWD treated with rVWF compared to pVWF (e.g., 1 U/ml rVWF vs. pVWF: 73.7±1.33 s vs. 231.3±43.4 s, p<0.01)

Conclusion

In summary, this study shows that rVWF compared to pVWF more effectively reduced PFA closures times in blood samples of ECMO patients with aVWS. Higher doses of VWF are needed to normalize PFA closure time in blood samples of patients with ECMO-induced aVWS compared to hereditary VWD. These data support the use of PFA-200 to monitor hemostatic effects in a future clinical trial involving ECMO patients with aVWS.
Multi-omics characterization of a scoring system to quantify hypoxia patterns in patients with head and neck squamous cell carcinoma
Authors: Peng Cong , Ye Huiping , li Zhengyang , Duan Xiaofeng , Yang Wen , Yi Zhuguang
Published: January 2023

Background

The 5-year survival rate of patients with head and neck squamous cell carcinoma (HNSCC) remains  < 50%. Hypoxia patterns are a hallmark of HNSCC that are associated with its occurrence and progression. However, the precise role of hypoxia during HNSCC, such as the relationship between hypoxia, tumor immune landscape and cell communication orchestration remains largely unknown. The current study integrated data from bulk and single-cell RNA sequencing analyses to define the relationship between hypoxia and HNSCC.

Methods

A scoring system named the hypoxia score (HS) was constructed based on hypoxia-related genes (HRGs) expression. The predictive value of HS response for patient outcomes and different treatments was evaluated. Single-cell datasets and cell communication were utilized to rule out cell populations which hypoxia targeted on.

Results

The survival outcomes, immune/Estimate scores, responses to targeted inhibitors, and chemotherapeutic, and immunotherapy responses were distinct between a high HS group and a low HS group (all P < 0.05). Single-cell datasets showed different distributions of HS in immune cell populations (P < 0.05). Furthermore, HLA-DPA1/CD4 axis was identified as a unique interaction between CD4 + T Conv and pDC cells.

Conclusions

Altogether, the quantification for hypoxia patterns is a potential biomarker for prognosis, individualized chemotherapeutic and immunotherapy strategies. The portrait of cell communication characteristics over the HNSCC ecosystem enhances the understanding of hypoxia patterns in HNSCC.
GSDMD-mediated pyroptosis dominantly promotes left ventricular remodeling and dysfunction in post-myocardial infarction: a comparison across modes of programmed cell death and mitochondrial involvement
Authors: Piamsiri Chanon , Maneechote Chayodom , Jinawong Kewarin , Arunsak Busarin , Chunchai Titikorn , Nawara Wichwara , Chattipakorn Siriporn C , Chattipakorn Nipon
Published: January 2023

Background

Myocardial infarction (MI) has recently accounted for more than one-third of global mortality. Multiple molecular pathological pathways, such as oxidative stress, inflammation, and mitochondrial dysfunction, have been recognized as possible mechanisms in the development of MI. Furthermore, different phases of ischemic injury following the progression of MI were also associated with multiple types of programmed cell death (PCDs), including apoptosis, necroptosis, ferroptosis, and pyroptosis. However, it remains unknown whether which types of PCDs play the most dominant role in post-myocardial infarction (post-MI).

Method

In this study, we used a preclinical rat model of MI induced by permanent left anterior descending coronary artery (LAD) ligation (n = 6) or a sham operated rat model (n = 6). After a 5-week experiment, cardiac function and morphology, mitochondrial studies, and molecular signaling analysis of PCDs were determined.

Results

Herein, we demonstrated that post-MI rats had considerably impaired cardiac geometry, increased oxidative stress, myocardial injuries, and subsequently contractile dysfunction. They also exhibited worsened cardiac mitochondrial function and dynamic imbalance. More importantly, we found that post-MI mediated abundant myocardial cell death through multiple PCDs, including apoptosis, necroptosis, and pyroptosis, but not ferroptosis.

Conclusion

In this study, we provide the first insights into the mechanism of PCDs by pyroptosis, which is leveraged as the most dominant mode of cell death after MI.
The SARS-CoV-2 nucleocapsid protein: its role in the viral life cycle, structure and functions, and use as a potential target in the development of vaccines and diagnostics
Authors: Wu Wenbing , Cheng Ying , Zhou Hong , Sun Changzhen , Zhang Shujun
Published: January 2023

Coronavirus disease 2019 (COVID-19) continues to take a heavy toll on personal health, healthcare systems, and economies around the globe. Scientists are expending tremendous effort to develop diagnostic technologies for detecting positive infections within the shortest possible time, and vaccines and drugs specifically for the prevention and treatment of COVID-19 disease. At the same time, emerging novel variants have raised serious concerns about vaccine efficacy. The SARS-CoV-2 nucleocapsid (N) protein plays an important role in the coronavirus life cycle, and participates in various vital activities after virus invasion. It has attracted a large amount of attention for vaccine and drug development. Here, we summarize the latest research of the N protein, including its role in the SARS-CoV-2 life cycle, structure and function, and post-translational modifications in addition to its involvement in liquid–liquid phase separation (LLPS) and use as a basis for the development of vaccines and diagnostic techniques.
Dosimetric quality of HyperArc in boost radiotherapy for single glioblastoma: comparison with CyberKnife and manual VMAT
Authors: Pan Mingyuan , Xu Wenqian , Sun Lei , Wang Chaozhuang , Dong Shengnan , Guan Yun , Yang Jun , Wang Enmin
Published: January 2023

Background

Stereotactic radiotherapy (SRT) and hypo-fractionated radiotherapy are feasible treatment options for single glioblastoma multiforme when combined with conventional radiotherapy or delivered alone. HyperArc (HA), a novel linac-based method with 4 noncoplanar arcs, has been introduced into stereotactic radiosurgery (SRS) for single and multiple metastases. In this study, we compared the dosimetric quality of HyperArc with the well-established CyberKnife (CK) and conventional VMAT methods of SRT for a single, large target.

Methods

Sixteen patients treated in our center with their clinical CK plans were enrolled, and the linac-based plans were designed in silico. From the aspect of normal tissue protection and treatment efficacy, we compared the conformity index (CI), gradient index (GI), homogeneity index (HI), dose distribution in planning target volume, dose in the normal brain tissue, and mean dose of several organs at risk (OARs). All of the data were evaluated with nonparametric Kruskal‒Wallis tests. We further investigated the relationship of the dose distribution with the tumor volume and its location.

Results

The results showed that with a higher CI (0.94 ± 0.03) and lower GI (2.57 ± 0.53), the HA plans generated a lower dose to the OARs and the normal tissue. Meanwhile, the CK plans achieved a higher HI (0.35 ± 0.10) and generated a higher dose inside the tumor. Although manual VMAT showed slight improvement in dose quality and less monitoring units (2083 ± 225), HA can save half of the delivery time of CK (37 minutes) on average.

Conclusion

HA plans have higher conformity and spare OARs with lower normal tissue irradiation, while CK plans achieve a higher mean dose in tumors. HA with 4 arcs is sufficient in dosimetric quality for a single tumor with great convenience in planning and treatment processes compared with conventional VMAT. The tumor size and location are factors to be considered when selecting treatment equipment.