bluuebunny/crossref_metadata_2025 huggingface dataset:
Core and conditionally rare taxa as indicators of agricultural drainage ditch and stream health and function
Authors: Shi Yichao , Khan Izhar U. H. , Radford Devon , Guo Galen , Sunohara Mark , Craiovan Emilia , Lapen David R. , Pham Phillip , Chen Wen
Published: March 2023

Background

The freshwater microbiome regulates aquatic ecological functionality, nutrient cycling, pathogenicity, and has the capacity to dissipate and regulate pollutants. Agricultural drainage ditches are ubiquitous in regions where field drainage is necessary for crop productivity, and as such, are first-line receptors of agricultural drainage and runoff. How bacterial communities in these systems respond to environmental and anthropogenic stressors are not well understood. In this study, we carried out a three year study in an agriculturally dominated river basin in eastern Ontario, Canada to explore the spatial and temporal dynamics of the core and conditionally rare taxa (CRT) of the instream bacterial communities using a 16S rRNA gene amplicon sequencing approach. Water samples were collected from nine stream and drainage ditch sites that represented the influence of a range of upstream land uses.

Results

The cross-site core and CRT accounted for 5.6% of the total number of amplicon sequence variants (ASVs), yet represented, on average, over 60% of the heterogeneity of the overall bacterial community; hence, well reflected the spatial and temporal microbial dynamics in the water courses. The contribution of core microbiome to the overall community heterogeneity represented the community stability across all sampling sites. CRT was primarily composed of functional taxa involved in nitrogen (N) cycling and was linked to nutrient loading, water levels, and flow, particularly in the smaller agricultural drainage ditches. Both the core and the CRT were sensitive responders to changes in hydrological conditions.

Conclusions

We demonstrate that core and CRT can be considered as holistic tools to explore the temporal and spatial variations of the aquatic microbial community and can be used as sensitive indicators of the health and function of agriculturally dominated water courses. This approach also reduces computational complexity in relation to analyzing the entire microbial community for such purposes.
Rapid, sensitive, and specific detection of SARS-CoV-2 in nasopharyngeal swab samples of suspected patients using a novel one-step loop-mediated isothermal amplification (one-step LAMP) technique
Authors: Khanizadeh Sayyad , Malekshahi Asra , Hanifehpour Hooman , Birjandi Mehdi , Fallahi Shirzad
Published: March 2023

Background

In the absence of effective antiviral drugs or vaccines, early and accurate detection of SARS-CoV-2 infection is essential to the COVID-19 pandemic. This study developed and evaluated a novel rapid One-Step LAMP assay to directly detect the SARS-CoV-2 RNA from nasopharyngeal (NP) swab samples of patients with suspected SARS-CoV-2 infection living in deprived areas in comparison to One-Step Real-time PCR.

Methods

Two hundred fifty-four NP swab samples from patients suspected of COVID-19 infection living in deprived western areas of Iran were tested by TaqMan One-Step RT-qPCR and fast One-Step LAMP assays. Tenfold serial dilutions of SARS-CoV-2 RNA standard strain where the viral copy number in each dilution was previously determined using the qPCR and various templates were used to investigate the analytical sensitivity and specificity of the One-Step LAMP assay in triplicate. Also, the efficacy and reliability of the method compared to TaqMan One-Step RT-qPCR were evaluated using SARS-CoV-2 positive and negative clinical samples.

Results

The results of the One-Step RT-qPCR and One-Step LAMP tests were positive in 131 (51.6%) and 127 (50%) participants, respectively. Based on Cohen’s kappa coefficient (κ), the agreement between the two tests was 97%, which was statistically significant (P < 0.001). The detection limit for the One-Step LAMP assay was 1 × 101 copies of standard SARS-CoV-2 RNA per reaction in less than an hour in triplicates. Negative results in all samples with non-SARS-CoV-2 templates represent 100% specificity.

Conclusions

The results showed that the One-Step LAMP assay is an efficient consistent technique for detecting SARS-CoV-2 among suspected individuals due to its simplicity, speed, low cost, sensitivity, and specificity. Therefore, it has great potential as a useful diagnostic tool for disease epidemic control, timely treatment, and public health protection, especially in poor and underdeveloped countries.
Lateral metabolome study reveals the molecular mechanism of cytoplasmic male sterility (CMS) in Chinese cabbage
Authors: Yang Huiju , Chen Mingwei , Hu Jingfeng , Lan Mei , He Jiangming
Published: March 2023

Background

Chinese cabbage is one of the most widely grown leafy vegetables in China. Cytoplasmic male sterility (CMS) is a maternally inherited trait that produces abnormal pollen during anther development, which is commonly seen in cruciferous vegetables. However, the molecular mechanism of Chinese cabbage CMS is not clear. In this study, the metabolome and hormone profiles of Chinese cabbage male sterile line (CCR20000) and sterile maintainer line (CCR20001) were analyzed in flower buds during normal stamen development and abnormal stamen development, respectively.

Results

A total of 556 metabolites were detected based on UPLC-MS/MS detection platform and database search, and the changes of hormones such as auxin, cytokinins, abscisic acid, jasmonates, salicylic acid, gibberellin acid and ethylene were analyzed. The results showed that compared with the male fertile line (MF), the male sterile line (MS) significantly decreased the content of flavonoids and phenolamides metabolites in the stamen dysplasia stage, accompanied by a large accumulation of glucosinolate metabolites. Meanwhile, the contents of GA9, GA20, IBA, tZ and other hormones in MS were significantly lower than those in MF strains. Further, by comparing the metabolome changes of MF and MS during stamen dysplasia, it was found that flavonoid metabolites and amino acid metabolites were distinctly different.

Conclusions

These results suggest that flavonoids, phenolamides and glucosinolate metabolites may be closely related to the sterility of MS strains. This study provides an effective basis for further research on the molecular mechanism of CMS in Chinese cabbage.
The burden of CDI in the United States: a multifactorial challenge
Authors: Feuerstadt Paul , Theriault Nicolette , Tillotson Glenn
Published: March 2023

Clostridioides difficile infection (CDI) affects approximately 500,000 patients annually in the United States, of these around 30,000 will die. CDI carries significant burdens including clinical, social and economic. While healthcare-associated CDI has declined in recent years, community-associated CDI is on the rise. Many patients are also impacted by recurrent C. difficile infections (rCDI); up to 35% of index CDI will recur and of these up to 60% will further recur with multiple recurrences observed. The range of outcomes adversely affected by rCDI is significant and current standard of care does not alter these recurrence rates due to the damaged gut microbiome and subsequent dysbiosis. The clinical landscape of CDI is changing, we discuss the impact of CDI, rCDI, and the wide range of financial, social, and clinical outcomes by which treatments should be evaluated.
Evaluation of under-testing and under-diagnosis of tick-borne encephalitis in Germany
Authors: Schley Katharina , Friedrich Josephine , Pilz Andreas , Huang Liping , Balkaran Bridget L. , Maculaitis Martine C. , Malerczyk Claudius
Published: March 2023

Background

Tick-borne encephalitis (TBE), a viral infectious disease affecting the central nervous system, potentially resulting in prolonged neurological symptoms and other long-term sequelae. Case identification can be challenging as TBE can be associated with non-specific symptoms, and even in cases consistent with typical TBE symptoms, the rate of laboratory testing to confirm cases is unknown. This study assessed real-world TBE laboratory testing rates across Germany.

Methods

In this retrospective cross-sectional study, physicians provided data on TBE decision-making, laboratory testing (serological), and diagnostics behavior via in-depth qualitative interviews (N = 12) or a web-based quantitative survey of their patient medical records (N = 166). Hospital-based physicians who specialized in infectious disease, intensive care unit, emergency room, neurology, or pediatrics with experience managing and ordering testing for patients with meningitis, encephalitis, or non-specific central nervous system symptoms in the past 12 months were included. Data were summarized via descriptive statistics. TBE testing and positivity rates were assessed for the aggregate sample of 1400 patient charts and reported by presenting symptoms, region, and tick bite exposure.

Results

TBE testing rates ranged from 54.0% (non-specific neurological symptoms only) to 65.6% (encephalitis symptoms only); the percentage of TBE positive results ranged from 5.3% (non-specific neurological symptoms only) to 36.9% (meningitis symptoms only). TBE testing rates were higher among those with a tick bite history and/or who presented with headache, high fever, or flu-like symptoms.

Conclusions

The findings of this study suggest that patients with typical TBE symptoms are likely under-tested, thus likely leading to under-diagnosis in Germany. To ensure appropriate case identification, TBE testing should be consistently integrated into routine practice for all patients who present with relevant symptoms or exposure to common risk factors.
Limitations on knowledge of autoimmune encephalitis and barriers to its treatment among neurologists: a survey from western China
Authors: Li Aiqing , Guo Kundian , Liu Xu , Gong Xue , Li Xingjie , Zhou Dong , Hong Zhen
Published: March 2023

Background

Autoimmune encephalitis (AE) is a group of severe antibody-mediated brain diseases. The understanding of clinical management of AE has developed rapidly. However, the knowledge level of AE and barriers to effective treatment among neurologists remains unstudied.

Methods

We conducted a questionnaire survey among neurologist in western China on knowledge of AE, treatment practices, and perspectives on barriers to treatment.

Results

A total of 1113 neurologists were invited and 690 neurologists from 103 hospitals completed the questionnaire with a response rate of 61.9%. Respondents correctly answered 68.3% of medical questions about AE. Some respondents (12.4%) never assayed for diagnostic antibodies if patients had suspected AE. Half (52.3%) never prescribed immunosuppressants for AE patients, while another 7.6% did not know whether they should do so. Neurologists who never prescribed immunosuppressants were more likely to have less education, a less senior job title, and to practice in a smaller setting. Neurologists who did not know whether to prescribe immunosuppressants were associated with less AE knowledge. The most frequent barrier to treatment, according to respondents, was financial cost. Other barriers to treatment included patient refusal, insufficient AE knowledge, lack of access to AE guidelines, drugs or diagnostic test, etc.

Conclusion

Neurologists in western China lack AE knowledge. Medical education around AE is urgent needed and should be more targeted to individuals with less educated level or working in non-academic hospitals. Policies should be developed to increase the availability of AE related antibody testing or drugs and reduce the economic burden of disease.
Prevalence and factors associated with insomnia among medical students in China during the COVID-19 pandemic: characterization and associated factors
Authors: Zhang Ming , Qin Li , Zhang Dongmei , Tao Mingfen , Han Kangrong , Chi Chenru , Zhang Zhongying , Tao Xiubin , Liu Huan
Published: March 2023

Background

Insomnia has become an important issue in recent years. Insomnia is affected by many factors. Previous research has shown that during the COVID-19 pandemic, there would be a long-term negative effect on the mental health of medical college students. The state of medical college students’ insomnia directly determines the results of medical education and the career development prospects of the medical students themselves. Therefore, it is very important to understand the insomnia situation of medical students in the post-epidemic era.

Methods

This study was conducted 2 years after the global COVID-19 pandemic (April 1-April 23, 2022). The study used an online questionnaire, administered through a web-based survey platform. The Athens Insomnia Scale (AIS), Fear of COVID‐19 Scale (FCV-19S), GAD-2, PHQ-2, and socio-demographic information were surveyed by the Questionnaire Star platform.

Results

The prevalence of insomnia was 27.80% (636/2289). Grade(P < 0.05), age(P < 0.001),

loneliness(P < 0.001), depression(P < 0.001), anxiety(P < 0.001), fear of COVID-19 was highly correlated with insomnia (P < 0.001). Adapting to online class(P < 0.001) was a protective factor of smartphone addiction.

Conclusions

This survey shows that Insomnia was highly prevalent among the Chinese medical college students during the COVID-19 pandemic. Governments and schools should through psychological interventions to address the current situation of insomnia among medical students, and formulate targeted programs and strategies to reduce their psychological problems.
The Arabic Questionnaire for Psychotic Experiences in patients with psychotic disorders: a clinical validation
Authors: Yehya Arij , Khaled Salma M. , Sommer Iris E. C. , Elhag Saba F. , Hassan Mohamed H. M. O. , Woodruff Peter , Alabdalla Majid
Published: March 2023

Background

Psychotic experiences are reported in the general population. The Questionnaire for Psychotic Experiences (QPE) was created to test the phenomenological features of these experiences and compare them with those reported in patients with psychiatric and other medical conditions. The aim of this study was to test the psychometric properties of the Arabic version of the QPE.

Methods

We recruited 50 patients with psychotic disorders from the Hamad Medical Hospital in Doha, Qatar. Patients underwent assessment over three sessions with trained interviewees using the Arabic versions of QPE, Positive and Negative Syndrome Scale (PANSS), Beck Depression Inventory (BDI), and the Global Assessment of Functioning Scale (GAF). Patients were also reassessed using the QPE and GAF after 14-days from the initial assessment in order to test for the stability of the scale. In this respect, this is the first study that assesses the test–retest reliability of the QPE. The psychometric properties including convergent validity, stability, and internal consistency met the benchmarked criteria.

Results

Results confirmed that the Arabic version of QPE accurately measured the experiences of patients that were also reported using the PANSS, an internationally accepted, well-established scale for measuring psychotic symptom severity.

Conclusion

We propose the use of the QPE to describe the phenomenology of PEs across modalities in Arabic speaking communities.
Community-based approaches to infant safe sleep and breastfeeding promotion: a qualitative study
Authors: Menon Meera , Huber Rebecca , West Dana D. , Scott Stacy , Russell Rebecca B. , Berns Scott D.
Published: March 2023

Background

In the U.S., sudden unexpected infant deaths (SUID) due to accidental suffocation and strangulation in bed (ASSB) are increasing, with disparities by race/ethnicity. While breastfeeding is a protective factor against infant mortality, racial/ethnic disparities are present in its uptake, and motivations to breastfeed are also often coupled with non-recommended infant sleep practices that are associated with infant sleep deaths. Combining infant safe sleep (ISS) and breastfeeding promotion on the community level presents opportunities to address racial/ethnic disparities and associated socioeconomic, cultural, and psychosocial influences.

Methods

We completed a descriptive qualitative hermeneutical phenomenology using thematic analysis of focus group data. We examined the phenomenon of community-level providers promoting ISS and breastfeeding in communities vulnerable to ISS and breastfeeding disparities. We asked eighteen informants participating in a national quality improvement collaborative about i.) areas requiring additional support to meet community needs around ISS and breastfeeding, and ii.) recommendations on tools to improve their work promoting ISS and breastfeeding.

Results

We identified four themes: i.) education and dissemination, ii.) relationship building and social support, iii.) working with clients’ personal circumstances and considerations, and iv.) tools and systems.

Conclusions

Our findings support embedding risk-mitigation approaches in ISS education; relationship building between providers, clients, and peers; and the provision of ISS and breastfeeding supportive material resources with educational opportunities. These findings may be used to inform community-level provider approaches to ISS and breastfeeding promotion.
HLA typing of patients who developed subacute thyroiditis and Graves’ disease after SARS-CoV-2 vaccination: a case report
Authors: Yasuda Shigemitsu , Suzuki Seiya , Yanagisawa Shinnosuke , Morita Hideo , Haisa Akifumi , Satomura Atsushi , Nakajima Ritsuko , Oikawa Yoichi , Inoue Ikuo , Shimada Akira
Published: March 2023

Background

Cases of subacute thyroiditis (SAT) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination have been reported. A human leukocyte antigen (HLA) allele, HLA-B*35, appears to be involved in the pathogenesis of SAT.

Case presentation

We conducted HLA typing of one patient with SAT and another with both SAT and Graves’ disease (GD), which developed after SARS-CoV-2 vaccination. Patient 1, a 58-year-old Japanese man, was inoculated with a SARS-CoV-2 vaccine (BNT162b2; Pfizer, New York, NY, USA). He developed fever (38 °C), cervical pain, palpitations, and fatigue on day 10 after vaccination. Blood chemistry tests revealed thyrotoxicosis and elevated serum C-reactive protein (CRP) and slightly increased serum antithyroid-stimulating antibody (TSAb) levels. Thyroid ultrasonography revealed the characteristic findings of SAT. Patient 2, a 36-year-old Japanese woman, was inoculated twice with a SARS-CoV-2 vaccine (mRNA-1273; Moderna, Cambridge, MA, USA). She developed fever (37.8 °C) and thyroid gland pain on day 3 after the second vaccination. Blood chemistry tests revealed thyrotoxicosis and elevated serum CRP, TSAb, and antithyroid-stimulating hormone receptor antibody levels. Fever and thyroid gland pain persisted. Thyroid ultrasonography revealed the characteristic findings of SAT (i.e., slight swelling and a focal hypoechoic area with decreased blood flow). Prednisolone treatment was effective for SAT. However, thyrotoxicosis causing palpitations relapsed thereafter, for which thyroid scintigraphy with 99mtechnetium pertechnetate was conducted, and the patient was diagnosed with GD. Thiamazole treatment was then initiated, which led to improvement in symptoms.

Conclusion

HLA typing revealed that both patients had the HLA-B*35:01, -C*04:01, and -DPB1*05:01 alleles. Only patient 2 had the HLA-DRB1*11:01 and HLA-DQB1*03:01 alleles. The HLA-B*35:01 and HLA-C*04:01 alleles appeared to be involved in the pathogenesis of SAT after SARS-CoV-2 vaccination, and the HLA-DRB1*11:01 and HLA-DQB1*03:01 alleles were speculated to be involved in the postvaccination pathogenesis of GD.
Subacute thyroiditis presenting as simple acute headache was misdiagnosed as meningitis: case report and literature review
Authors: Huang Cao , Shen Shuang , Yao Jianping
Published: March 2023

Background

The relationship between headache and thyrotoxicosis has been occasionally mentioned in case reports, but there are few related reports. Thus, the relationship cannot be determined. Few cases of subacute thyroiditis (SAT) presenting as simple headache have been reported.

Case presentation

This case report describes a middle-aged male patient who came to our hospital with acute headache for 10 days. He was initially misdiagnosed as meningitis due to headache, fever, and increased C-reactive protein. Routine antibacterial and antiviral therapy did not improve his symptoms. Blood test suggested thyrotoxicosis, and color ultrasound suggested SAT sonography. He was diagnosed with SAT. With the treatment of SAT, the headache was relieved after the thyrotoxicosis improved.

Conclusion

This patient is the first detailed report of SAT presenting with simple headache, which is helpful for clinicians to differentiate and diagnose atypical SAT.
The relationship between diet quality indices and odds of breast cancer in women: a case–control study
Authors: Sohouli Mohammad Hassan , Buckland Genevieve , Clark Cain C. T. , Santos Heitor O. , Athayde Felipe L. , Sanati Vahid , Janani Leila , Sajadian Akram Sadat , Zarrati Mitra
Published: March 2023

Dietary quality is an important factor in the etiology of breast cancer (BrCa), but further studies are required to better elucidate this relationship. Accordingly, we sought to analyze if diet quality, assessed using the Diet Quality Index-International (DQI-I), Mean Adequacy Ratio (MAR), and Dietary Energy Density (DED), was related to BrCa. In this Hospital-based case–control study, 253 patients with BrCa and 267 non BrCa controls were enrolled. Individual food consumption data from a food frequency questionnaire was used to calculate the Diet Quality Indices (DQI). Employing a case–control design, odds ratios (ORs) and 95% confidence intervals (CIs) were obtained, and a dose–response analysis investigated. After adjusting for potential confounders, those in the highest quartile of the MAR index had significantly lower odds of BrCa than those in the lowest (OR = 0.42, 95% CI 0.23–0.78; P for trend = 0.007). Although there was no association between individual quartiles of the DQI-I and BrCa, there was evidence of a significant trend across all the quartile categories (P for trend = 0.030).There was no significant association was found between DED index and the odds of BrCa in the crude and fully adjusted models. We found that higher MAR indices were associated with decreased odds of BrCa, Therefore, the dietary patterns reflected by these scores may serve as a possible guide to preventing BrCa in Iranian women.
Can a novel constructivist theory-informed feedback intervention reduce prescribing errors ? A pre-post study
Authors: Coombes Ian , Donovan Peter , Bullock Brooke , Mitchell Charles , Noble Christy
Published: March 2023

Context

Medical interns (interns) find prescribing challenging and many report lacking readiness when commencing work. Errors in prescribing puts patients’ safety at risk. Yet error rates remain high, despite education, supervision and pharmacists’ contributions. Feedback on prescribing may improve performance. Yet, work-based prescribing feedback practices focus on rectifying errors. We aimed to explore if prescribing can be improved using a theory-informed feedback intervention.

Methods

In this pre-post study, we designed and implemented a constructivist-theory informed prescribing feedback intervention, informed by Feedback-Mark 2 Theory. Interns commencing internal medicine terms in two Australian teaching hospitals were invited to engage in the feedback intervention. Their prescribing was evaluated by comparing errors per medication order of at least 30 orders per intern. Pre/baseline (weeks 1–3) were compared with post intervention (weeks 8–9). Interns’ baseline prescribing audit findings were analysed and discussed at individualised feedback sessions. These sessions were with a clinical pharmacologist (Site 1) and a pharmacist educator (Site 2).

Results

Eighty eight intern’s prescribing over five 10-week terms was analysed from two hospitals. The frequency of prescribing errors significantly reduced at both sites after the intervention, across all five terms (p < 0.001).There were initially 1598 errors in 2750 orders (median [IQR] 0.48 [0.35–0.67] errors per order) and after the intervention 1113 errors in 2694 orders (median [IQR] 0.30 [0.17–0.50] errors per order).

Conclusion

Our findings suggest interns’ prescribing practices may improve as a result of constructivist -theory learner centred, informed feedback with an agreed plan. This novel intervention, contributed, to a reduction in interns’ prescribing errors. This study suggests new strategies for improving prescribing safety should include the design and implementation of theory-informed feedback interventions.
Exploration of how primary care models influence job satisfaction among primary care providers during the COVID-19 pandemic in New Brunswick: a descriptive and comparative study
Authors: Johnson Claire , Bourgoin Dominique , Dupuis Jérémie B. , Félix Jenny Manuèle , LeBlanc Véronique , McLennan Danielle , St-Louis Luveberthe
Published: March 2023

Background

The COVID-19 pandemic has highlighted human resource gaps and physician shortages in healthcare systems in New Brunswick (NB), as evidenced by multiple healthcare service interruptions. In addition, the New Brunswick Health Council gathered data from citizens on the type of primary care models (i.e. physicians in solo practice, physicians in collaborative practice, and collaborative practice with physicians and nurse practitioners) they use as their usual place of care. To add to their survey’s findings, our study aims to see how these different primary care models were associated with job satisfaction as reported by primary care providers.

Methods

In total, 120 primary care providers responded to an online survey about their primary care models and job satisfaction levels. We used IBM’s “SPSS Statistics” software to run Chi-square and Fisher’s exact tests to compare job satisfaction levels between variable groups to determine if there were statistically significant variations.

Results

Overall, 77% of participants declared being satisfied at work. The reported job satisfaction levels did not appear to be influenced by the primary care model. Participants reported similar job satisfaction levels regardless of if they practiced alone or in collaboration. Although 50% of primary care providers reported having symptoms of burnout and experienced a decline in job satisfaction during the COVID-19 pandemic, the primary care model was not associated with these experiences. Therefore, participants who reported burnout or a decline in job satisfaction were similar in all primary care models. Our study’s results suggest that the autonomy to choose a preferred model was important, since 45.8% of participants reported choosing their primary care models, based on preference. Proximity to family and friends and balancing work and family emerged as critical factors that influence choosing a job and staying in that job.

Conclusion

Primary care providers’ staffing recruitment and retention strategies should include the factors reported as determinants in our study. Primary care models do not appear to influence job satisfaction levels, although having the autonomy to choose a preferred model was reported as highly important. Consequently, it may be counterproductive to impose specific primary care models if one aims to prioritize primary care providers’ job satisfaction and wellness.
Germans’ awareness of refugees’ information barriers regarding health care access: a cross-sectional study
Authors: Schubert Saskia , Kluge Ulrike , Klapprott Felix , Ringeisen Tobias
Published: March 2023

Background

In light of their experiences on the refuge and upon their arrival in the receiving society, refugees may have differentiated needs regarding health care. However, negative attitudes of the members of the receiving society and a lack of information pose as barriers for refugees when trying to access health care services. In that sense, it is largely unknown, which antecedents positively affect Germans’ perception of information barriers that refugees face. Based on an extended version of the Empathy-Attitude-Action model, this study examined selected predictors of problem awareness in the form of perceived information barriers that refugees face, emphasizing the role of positive intercultural contact experiences.

Methods

A sample of members of the receiving society, here: Germans (N = 910) completed a cross-sectional online survey with validated self-report measures. From the perspective of Germans, assessments covered positive intercultural contact, attitudes on refugees’ rights, the recognition of refugees’ socio-emotional support needs as a form of cognitive empathy, and the perception of refugees’ information barriers when accessing health care. We conducted structural equation modeling to examine hypothesized latent associations and specified three different models with unidirectional paths between the study variables, each allowing another direct path from intercultural contact to the variables. We determined the best model using the chi-square-difference test and tested for indirect effects along the paths through bias-corrected bootstrapping.

Results

Our results show consistency with the Empathy-Attitude-Action model. We found Germans’ cognitive empathy toward refugees to be associated with more positive attitudes and a greater awareness of refugees’ information barriers. We further found more positive intercultural contact to be associated with greater cognitive empathy toward refugees and with more positive attitudes. While these contact experiences showed a slightly direct negative effect on Germans’ perception of refugees’ information barriers to accessing health care, the indirect effects via cognitive empathy and positive attitudes were positive.

Conclusion

Previous positive intercultural contact may be directly and indirectly linked to greater awareness for refugees, helping Germans as the receiving community (1) to become more empathetic toward refugees, (2) to improve their attitudes toward refugees’ rights and to (3) raise consciousness for information barriers that refugees face when trying to access health care services.
Association of gastric inhibitory polypeptide receptor (GIPR) gene polymorphism with type 2 diabetes mellitus in iranian patients
Authors: Erfanian Saiedeh , Mir Hamed , Abdoli Amir , Roustazadeh Abazar
Published: March 2023

Introduction

Gastric inhibitory polypeptide receptor (GIPR) encodes a G-protein coupled receptor for gastric inhibitory polypeptide (GIP), which was demonstrated to stimulate insulin secretion. Relation of GIPR gene variation to impaired insulin response has been suggested in previous studies. However, little information is available regarding GIPR polymorphisms and type 2 diabetes mellitus (T2DM). Hence, the aim of the study was to investigate single nucleotide polymorphisms (SNPs) in the promoter and coding regions of GIPR in Iranian T2DM patients.

Materials and methods

Two hundred subjects including 100 healthy and 100 T2DM patients were recruited in the study. Genotypes and allele frequency of rs34125392, rs4380143 and rs1800437 in the promoter, 5ʹ UTR and coding region of GIPR were investigated by RFLP-PCR and Nested-PCR.

Results

Our finding indicated that rs34125392 genotype distribution was statistically different between T2DM and healthy groups (P = 0.043). In addition, distribution of T/- + -/- versus TT was significantly different between the both groups (P = 0.021). Moreover, rs34125392 T/- genotype increased the risk of T2DM (OR = 2.68, 95%CI = 1.203–5.653, P = 0.015). However, allele frequency and genotype distributions of rs4380143 and rs1800437 were not statistically different between the groups (P > 0.05). Multivariate analysis showed that the tested polymorphisms had no effect on biochemical variables.

Conclusion

We concluded that GIPR gene polymorphism is associated with T2DM. In addition; rs34125392 heterozygote genotype may increase the risk of T2DM. More studies with large sample size in other populations are recommended to show the ethnical relation of these polymorphisms to T2DM.
Exercise activates Sirt1-mediated Drp1 acetylation and inhibits hepatocyte apoptosis to improve nonalcoholic fatty liver disease
Authors: Hu Zongqiang , Zhang Hongyu , Wang Yiting , Li Boyi , Liu Kaiyu , Ran Jianghua , Li Li
Published: March 2023

Purpose

Aerobic exercise has shown beneficial effects in the prevention and treatment of non-alcoholic fatty liver disease (NAFLD). Nevertheless, the regulatory mechanism is not turely clear. Therefore, we aim to clarify the possible mechanism by investigating the effects of aerobic exercise on NAFLD and its mitochondrial dysfunction.

Methods

NAFLD rat model was established by feeding high fat diet. and used oleic acid (OA) to treat HepG2 cells. Changes in histopathology, lipid accumulation, apoptosis, body weight, and biochemical parameters were assessed. In addition, antioxidants, mitochondrial biogenesis and mitochondrial fusion and division were assessed.

Results

The obtained in vivo results showed that aerobic exercise significantly improved lipid accumulation and mitochondrial dysfunction induced by HFD, activated the level of Sirtuins1 (Srit1), and weakened the acetylation and activity of dynamic-related protein 1 (Drp1). In vitro results showed that activation of Srit1 inhibited OA-induced apoptosis in HepG2 cells and alleviated OA-induced mitochondrial dysfunction by inhibiting Drp1 acetylation and reducing Drp1 expression.

Conclusion

Aerobic exercise alleviates NAFLD and its mitochondrial dysfunction by activating Srit1 to regulate Drp1 acetylation. Our study clarifies the mechanism of aerobic exercise in alleviating NAFLD and its mitochondrial dysfunction and provides a new method for adjuvant treatment of NAFLD.
Uterine luminal-derived extracellular vesicles: potential nanomaterials to improve embryo implantation
Authors: Hong Linjun , Zang Xupeng , Hu Qun , He Yanjuan , Xu Zhiqian , Xie Yanshe , Gu Ting , Yang Huaqiang , Yang Jie , Shi Junsong , Zheng Enqin , Huang Sixiu , Xu Zheng , Liu Dewu , Cai Gengyuan , Li Zicong , Wu Zhenfang
Published: March 2023

Most pregnancy losses worldwide are caused by implantation failure for which there is a lack of effective therapeutics. Extracellular vesicles are considered potential endogenous nanomedicines because of their unique biological functions. However, the limited supply of ULF-EVs prevents their development and application in infertility diseases such as implantation failure. In this study, pigs were used as a human biomedical model, and ULF-EVs were isolated from the uterine luminal. We comprehensively characterized the proteins enriched in ULF-EVs and revealed their biological functions in promoting embryo implantation. By exogenously supplying ULF-EVs, we demonstrated that ULF-EVs improve embryo implantation, suggesting that ULF-EVs are a potential nanomaterial to treat implantation failure. Furthermore, we identified that MEP1B is important in improving embryo implantation by promoting trophoblast cell proliferation and migration. These results indicated that ULF-EVs can be a potential nanomaterial to improve embryo implantation.
Developing a predictive model for clinically significant prostate cancer by combining age, PSA density, and mpMRI
Authors: Ma Zengni , Wang Xinchao , Zhang Wanchun , Gao Kaisheng , Wang Le , Qian Lixia , Mu Jingjun , Zheng Zhongyi , Cao Xiaoming
Published: March 2023

Purpose

The study aimed to construct a predictive model for clinically significant prostate cancer (csPCa) and investigate its clinical efficacy to reduce unnecessary prostate biopsies.

Methods

A total of 847 patients from institute 1 were included in cohort 1 for model development. Cohort 2 included a total of 208 patients from institute 2 for external validation of the model. The data obtained were used for retrospective analysis. The results of magnetic resonance imaging were obtained using Prostate Imaging Reporting and Data System version 2.1 (PI-RADS v2.1). Univariate and multivariate analyses were performed to determine significant predictors of csPCa. The diagnostic performances were compared using the receiver operating characteristic (ROC) curve and decision curve analyses.

Results

Age, prostate-specific antigen density (PSAD), and PI-RADS v2.1 scores were used as predictors of the model. In the development cohort, the areas under the ROC curve (AUC) for csPCa about age, PSAD, PI-RADS v2.1 scores, and the model were 0.675, 0.823, 0.875, and 0.938, respectively. In the external validation cohort, the AUC values predicted by the four were 0.619, 0.811, 0.863, and 0.914, respectively. Decision curve analysis revealed that the clear net benefit of the model was higher than PI-RADS v2.1 scores and PSAD. The model significantly reduced unnecessary prostate biopsies within the risk threshold of > 10%.

Conclusions

In both internal and external validation, the model constructed by combining age, PSAD, and PI-RADS v2.1 scores exhibited excellent clinical efficacy and can be utilized to reduce unnecessary prostate biopsies.
Platelet-derived microparticles stimulate the invasiveness of colorectal cancer cells via the p38MAPK-MMP-2/MMP-9 axis
Authors: Kassassir Hassan , Papiewska-Pająk Izabela , Kryczka Jakub , Boncela Joanna , Kowalska M. Anna
Published: March 2023

Background

Metastasis is the main cause of death in patients with colorectal cancer (CRC). Apart from platelets, platelet-derived microparticles (PMPs) are also considered important factors that can modify the activity of cancer cells. PMPs are incorporated by cancer cells and can also serve as intracellular signalling vesicles. PMPs are believed to affect cancer cells by upregulating their invasiveness. To date, there is no evidence that such a mechanism occurs in colorectal cancer. It has been shown that platelets can stimulate metalloproteases (MMPs) expression and activity via the p38MAPK pathway in CRC cells, leading to their elevated migratory potential. This study aimed to investigate the impact of PMPs on the invasive potential of CRC cells of various phenotypes via the MMP-2, MMP-9 and p38MAPK axis.

Methods

We used various CRC cell lines, including the epithelial-like HT29 and the mesenchymal-like SW480 and SW620. Confocal imaging was applied to study PMP incorporation into CRC cells. The presence of surface receptors on CRC cells after PMP uptake was evaluated by flow cytometry. Transwell and scratch wound-healing assays were used to evaluate cell migration. The level of C-X-C chemokine receptor type 4 (CXCR4), MMP-2, and MMP-9 and the phosphorylation of ERK1/2 and p38MAPK were measured by western blot. MMP activity was determined using gelatine-degradation assays, while MMP release was evaluated by ELISA.

Results

We found that CRC cells could incorporate PMPs in a time-dependent manner. Moreover, PMPs could transfer platelet-specific integrins and stimulate the expression of integrins already present on tested cell lines. While mesenchymal-like cells expressed less CXCR4 than epithelial-like CRC cells, PMP uptake did not increase its intensity. No significant changes in CXCR4 level either on the surface or inside CRC cells were noticed. Levels of cellular and released MMP-2 and MMP-9 were elevated in all tested CRC cell lines after PMP uptake. PMPs increased the phosphorylation of p38MAPK but not that of ERK1/2. Inhibition of p38MAPK phosphorylation reduced the PMP-induced elevated level and release of MMP-2 and MMP-9 as well as MMP-dependent cell migration in all cell lines.

Conclusions

We conclude that PMPs can fuse into both epithelial-like and mesenchymal-like CRC cells and increase their invasive potential by inducing the expression and release of MMP-2 and MMP-9 via the p38MAPK pathway, whereas CXCR4-related cell motility or the ERK1/2 pathway appears to not be affected by PMPs.
Microglia specific deletion of miR-155 in Alzheimer’s disease mouse models reduces amyloid-β pathology but causes hyperexcitability and seizures
Authors: Aloi Macarena S. , Prater Katherine E. , Sánchez Raymond E. A. , Beck Asad , Pathan Jasmine L. , Davidson Stephanie , Wilson Angela , Keene C. Dirk , de la Iglesia Horacio , Jayadev Suman , Garden Gwenn A.
Published: March 2023

Alzheimer’s Disease (AD) is characterized by the accumulation of extracellular amyloid-β (Aβ) as well as CNS and systemic inflammation. Microglia, the myeloid cells resident in the CNS, use microRNAs to rapidly respond to inflammatory signals. MicroRNAs (miRNAs) modulate inflammatory responses in microglia, and miRNA profiles are altered in Alzheimer’s disease (AD) patients. Expression of the pro-inflammatory miRNA, miR-155, is increased in the AD brain. However, the role of miR-155 in AD pathogenesis is not well-understood. We hypothesized that miR-155 participates in AD pathophysiology by regulating microglia internalization and degradation of Aβ. We used CX3CR1CreER/+ to drive-inducible, microglia-specific deletion of floxed miR-155 alleles in two AD mouse models. Microglia-specific inducible deletion of miR-155 in microglia increased anti-inflammatory gene expression while reducing insoluble Aβ1-42 and plaque area. Yet, microglia-specific miR-155 deletion led to early-onset hyperexcitability, recurring spontaneous seizures, and seizure-related mortality. The mechanism behind hyperexcitability involved microglia-mediated synaptic pruning as miR-155 deletion altered microglia internalization of synaptic material. These data identify miR-155 as a novel modulator of microglia Aβ internalization and synaptic pruning, influencing synaptic homeostasis in the setting of AD pathology.
Assessing the value of bypassing agent therapy used prophylactic versus on-demand, during immune tolerance induction for treatment of inhibitors: a retrospective chart review
Authors: Morgan George , Back Emily , Rosa Doug , O’Hara Jamie , Finnegan Alan
Published: March 2023

Background

Haemophilia A is a bleeding disorder caused by deficiency of coagulation factor VIII (FVIII) which leads to severe and repeated bleedings. There is a need to understand the optimal treatment pathway for FVIII inhibitors with the use of immune tolerance induction (ITI) and the role of haemostatic ‘bypassing’ agents (BPA) on-demand (OD) or prophylactically (Px). The aim of this study was to gain a better understanding of the real-world use of BPA therapy administered prophylactically or on-demand concomitant with ITI, for the treatment of an inhibitor to FVIII replacement therapy in patients with severe haemophilia A.

Methods

Retrospective observational data were used to capture disease management information for patients who were aged 16 or under and had received ITI and BPA treatment for their most recent inhibitor from Jan-2015 to Jan-2019, for 47 patients in the UK and Germany. Descriptive comparisons of the clinical effectiveness and resource utilisation of Px and OD BPA therapy during ITI were conducted.

Results

During ITI and BPA treatment, for an inhibitor, bleeding events averaged 1.5 and 1.2 for Px and OD treatment respectively. Compared to only BPA therapy we see 3.4 and 1.4 bleeding events for Px and OD respectively during an inhibitor.

Conclusion

Baseline disease characteristics differed between BPA therapy cohorts and this resulted in higher clinical effectiveness of ITI treatment alongside BPA Px than BPA OD during an inhibitor.
Properties of Nav1.8ChR2-positive and Nav1.8ChR2-negative afferent mechanoreceptors in the hindpaw glabrous skin of mice
Authors: Yamada Akihiro , Yamada Ayaka I. , Ling Jennifer , Furue Hidemasa , Luo Wenqin , Gu Jianguo G.
Published: March 2023

Nav1.8-positive afferent fibers are mostly nociceptors playing a role in mediating thermal and mechanical pain, but mechanoreceptors within these afferents have not been fully investigated. In this study, we generated mice expressing channel rhodopsin 2 (ChR2) in Nav1.8-positive afferents (Nav1.8ChR2), which showed avoidance responses to mechanical stimulation and nocifensive responses to blue light stimulation applied to hindpaws. Using ex vivo hindpaw skin-tibial nerve preparations made from these mice, we characterized properties of mechanoreceptors on Nav1.8ChR2-positive and Nav1.8ChR2-negative afferent fibers that innervate the hindpaw glabrous skin. Of all Aβ-fiber mechanoreceptors, small portion was Nav1.8ChR2-positive. Of all Aδ-fiber mechanoreceptors, more than half was Nav1.8ChR2-positive. Of all C-fiber mechanoreceptors, almost all were Nav1.8ChR2-positive. Most Nav1.8ChR2-positive Aβ-, Aδ-, and C-fiber mechanoreceptors displayed slowly adapting (SA) impulses in response to sustained mechanical stimulation, and their mechanical thresholds were high in the range of high threshold mechanoreceptors (HTMRs). In contrast, sustained mechanical stimulation applied to Nav1.8ChR2-negative Aβ- and Aδ-fiber mechanoreceptors evoked both SA and rapidly adapting (RA) impulses, and their mechanical thresholds were in the range of low threshold mechanoreceptors (LTMRs). Our results provide direct evidence that in the mouse glabrous skin, most Nav1.8ChR2-negative Aβ-, Aδ-fiber mechanoreceptors are LTMRs involving in the sense of touch, whereas Nav1.8ChR2-positive Aβ-, Aδ-, and C-fiber mechanoreceptors are mainly HTMRs involving in mechanical pain.
Prolactin levels and breast cancer risk by tumor expression of prolactin-related markers
Authors: Hathaway Cassandra A. , Rice Megan S. , Collins Laura C. , Chen Dilys , Frank David A. , Walker Sarah , Clevenger Charles V. , Tamimi Rulla M. , Tworoger Shelley S. , Hankinson Susan E.
Published: March 2023

Background

Higher circulating prolactin has been associated with increased breast cancer risk. Prolactin binding to the prolactin receptor (PRLR) can activate the transcription factor STAT5, thus, we examined the association between plasma prolactin and breast cancer risk by tumor expression of PRLR, STAT5, and the upstream kinase JAK2.

Methods

Using data from 745 cases and 2454 matched controls in the Nurses’ Health Study, we conducted polytomous logistic regression to examine the association between prolactin (> 11 ng/mL vs. ≤ 11 ng/mL) measured within 10 years of diagnosis and breast cancer risk by PRLR (nuclear [N], cytoplasmic [C]), phosphorylated STAT5 (pSTAT5; N, C), and phosphorylated JAK2 (pJAK2; C) tumor expression. Analyses were conducted separately in premenopausal (n = 168 cases, 765 controls) and postmenopausal women (n = 577 cases, 1689 controls).

Results

In premenopausal women, prolactin levels > 11 ng/mL were positively associated with risk of tumors positive for pSTAT5-N (OR 2.30, 95% CI 1.02–5.22) and pSTAT5-C (OR 1.64, 95% CI 1.01–2.65), but not tumors that were negative for these markers (OR 0.98, 95% CI 0.65–1.46 and OR 0.73, 95% CI 0.43–1.25; p-heterogeneity = 0.06 and 0.02, respectively). This was stronger when tumors were positive for both pSTAT5-N and pSTAT5-C (OR 2.88, 95% CI 1.14–7.25). No association was observed for PRLR or pJAK2 (positive or negative) and breast cancer risk among premenopausal women. Among postmenopausal women, plasma prolactin levels were positively associated with breast cancer risk irrespective of PRLR, pSTAT5, or pJAK2 expression (all p-heterogeneity ≥ 0.21).

Conclusion

We did not observe clear differences in the association between plasma prolactin and breast cancer risk by tumor expression of PRLR or pJAK2, although associations for premenopausal women were observed for pSTAT5 positive tumors only. While additional studies are needed, this suggests that prolactin may act on human breast tumor development through alternative pathways.