bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of long-term effects of metformin on longevity between people with type 2 diabetes and matched non-diabetic controls
Authors: Stevenson-Hoare Joshua , Leonenko Ganna , Escott-Price Valentina
Published: May 2023

Background

Metformin, a medication for type 2 diabetes, has been linked to many non-diabetes health benefits including increasing healthy lifespan. Previous work has only examined the benefits of metformin over periods of less than ten years, which may not be long enough to capture the true effect of this medication on longevity.

Methods

We searched medical records for Wales, UK, using the Secure Anonymised Information Linkage dataset for type 2 diabetes patients treated with metformin (N = 129,140) and sulphonylurea (N = 68,563). Non-diabetic controls were matched on sex, age, smoking, and history of cancer and cardiovascular disease. Survival analysis was performed to examine survival time after first treatment, using a range of simulated study periods.

Findings

Using the full twenty-year period, we found that type 2 diabetes patients treated with metformin had shorter survival time than matched controls, as did sulphonylurea patients. Metformin patients had better survival than sulphonylurea patients, controlling for age. Within the first three years, metformin therapy showed a benefit over matched controls, but this reversed after five years of treatment.

Interpretation

While metformin does appear to confer benefits to longevity in the short term, these initial benefits are outweighed by the effects of type 2 diabetes when patients are observed over a period of up to twenty years. Longer study periods are therefore recommended for studying longevity and healthy lifespan.

Evidence before this study

Work examining the non-diabetes outcomes of metformin therapy has suggested that there metformin has a beneficial effect on longevity and healthy lifespan. Both clinical trials and observational studies broadly support this hypothesis, but tend to be limited in the length of time over which they can study patients or participants.

Added value of this study

By using medical records we are able to study individuals with Type 2 diabetes over a period of two decades. We are also able to account for the effects of cancer, cardiovascular disease, hypertension, deprivation, and smoking on longevity and survival time following treatment.

Implications of all the available evidence

We confirm that there is an initial benefit to longevity of metformin therapy, but this benefit does not outweigh the negative effect on longevity of diabetes. Therefore, we suggest that longer study periods are required for inference to be made about longevity in future research.
Prevalence and factors associated with sexual and reproductive health services use among reproductive age women with disabilities: a community based cross-sectional study
Authors: Rade Bayew Kelkay , Tamiru Animut Tagele , Aynalem Getie Lake , Taye Eden Bishaw , Melkie Mamaru , Abera Alamirew , Cherkos Endeshaw Admassu , Asaye Mengstu Melkamu
Published: May 2023

Background

According to International Convention on the Right of Person with Disabilities (CRPD), all nations should discern Sexual and Reproductive Health (SRH) as human rights and needs of all people living with disabilities. Women and girls with disabilities are highly vulnerable to SRH disparities including unintended pregnancy, acquiring sexual transmitted infections and unsafe abortion. Little has known about SRH service uptake and influencing factors among reproductive aged women living with disabilities.

Methods

A community-based cross-sectional study was conducted from January 1–30, 2021, the central Gondar zone selected districts. A total of 535 reproductive-age (18–49 years) women with disabilities had been interviewed through face-to-face using structured questionnaire. Multistage cluster sampling method was applied. A binary logistic regression model was computed to look the relationship between independent variables and uptake of SRH, and p-value < 0.05 was a cut-off point to declare statistical significance.

Results

A total of 33.27% (178/535) women with disabilities used at least one SRH service in the last twelve months preceding the survey. Those who had three or more children [AOR = 4.85; 95% CI (1.24–9.71)], autonomy to visit health care facilities [AOR = 3.30; 95% CI (1.45–6.92)], lived with sexual partner [AOR = 9.2; 95% CI (2.84–13.60)], subjected to radio/television in daily bases [AOR = 5.9; 95% CI (1.26–13.04)], autonomy to visit friends and relatives [AOR = 3.95; 95% CI (1.28–12.17)], had a discussion with family members about sexual and reproductive health [AOR = 9.36; 95% CI (3.44–17.47)], and engaged in sexual activity after the age of 18 years [AOR = 7.2; 95% CI (2.51–14.45)] were important predictors for service uptake.

Conclusions

Only one in three reproductive age women with disabilities used at least one SRH service. These findings suggest that accessing information through mainstream media exposure, having full autonomous to visit friends and families, open discussion with family members, live with sexual partner, having optimal family size and starting sexual act at the recommended age improve the uptake of SRH services. Therefore, the stakeholders (both governmental and non-governmental) need to make efforts to increase the uptake of SRH services.
Effective formative assessment for pharmacy students in Thailand: lesson learns from a school of pharmacy in Thailand
Authors: Sottiyotin Tida , Uitrakul Suriyon , Sakdiset Pajaree , Sukkarn Bhudsaban , Sangfai Thanachaporn , Chuaboon Litavadee , Palee Patsamon
Published: May 2023

Introduction

: Formative assessment (FA) is an assessment concept that is of interest in education. The Doctor of Pharmacy program is one of the programs in which FA is usually implemented. This study aimed to describe the correlation between FA scores and summative assessment (SA) scores and to suggest possible key success factors that affect the effectiveness of FA.

Methods

This study employed a retrospective design using mixed methods for data collection. Data in the semesters 1/2020 and 2/2020 of the Doctor of Pharmacy curriculum in a Thailand pharmacy school were used. Three sets of data were gathered, including the course information (e.g. FA methods, FA scores, and SA scores) from 38 records, self-reports from 326 students and 27 teachers, and 5 focus group discussions. The quantitative data were statistically analyzed using descriptive statistics and Pearson correlation, while the qualitative data were analyzed using a content analysis framework.

Results

The analysis revealed five main methods that were used for FA, including individual quizzes, individual reports, individual skill assessments, group presentations, and group reports. Of all 38 courses, 29 (76.32%) had significant correlations between FA and SA scores at p-values < 0.05. The individual FA score was related to the correlation coefficient of the courses (p-value = 0.007), but the group FA score was not related (p-value = 0.081). In addition, only the frequency of individual quiz had a significant effect on the correlation coefficient. Moreover, the key success factors which affected the effectiveness of FA were divided into six themes, including the appropriate method, an effective reflection, frequency of assessment, the appropriate score, the adequate support system, and teacher knowledge management.

Conclusion

The subjects that used individual FA methods provided a significant correlation between FA and SA, while those who used group FA methods did not show a significant correlation. Additionally, the key success factors in this study were appropriate assessment methods, frequency of assessment, effective feedback, appropriate scoring, and a proper support system.
Assessing cultural safety in general practice consultations for Indigenous patients: protocol for a mixed methods sequential embedded design study
Authors: Brumpton Kay , Ward Raelene , Evans Rebecca , Neill Henry , Woodall Hannah , McArthur Lawrie , Sen Gupta Tarun
Published: May 2023

Background

Assessment of cultural safety in general practice consultations for Indigenous patients is a complex notion. Design and development of any assessment tool needs to be cognizant that cultural safety is determined by Indigenous peoples and incorporates defined components of cultural safety and current educational theory. Consideration of how social, historical, and political determinants of health and well-being impact upon the cultural safety of a consultation is also important. Given this complexity, we assume that no single method of assessment will be adequate to determine if general practice (GP) registrars are demonstrating or delivering culturally safe care. As such, we propose that development and assessment of cultural safety can be conceptualised using a model that considers these variables. From this, we aim to develop a tool to assess whether GP registrars are conducting a culturally safe consultation, where cultural safety is determined by Aboriginal and Torres Strait Islander peoples.

Methods

This protocol will be situated in a pragmatic philosophical position to explore cultural safety primarily from the Australian Aboriginal and Torres Strait Islander patients’ perspective with triangulation and validation of findings with the GP and GP registrar perspective, the Aboriginal and Torres Strait Islander community, and the medical education community. The study will integrate both quantitative and qualitative data through three sequential phases. Data collection will be through survey, semi-structured interviews, an adapted nominal group technique, and a Delphi questionnaire. We aim to recruit approximately 40 patient and 20 GP participants for interviews, conduct one to five nominal groups (seven to 35 participants) and recruit fifteen participants for the Delphi process. Data will be analysed through a content analysis approach to identify components of an assessment of cultural safety for GP registrars.

Discussion

This study will be one of the first to explore how cultural safety, as determined by Indigenous peoples, can be assessed in general practice consultations. This protocol is shared to stimulate awareness and discussion around this significant issue and prompt other studies in this area.
The reliability and validity of the training elements scale for clinicians in the new era——based on the perspective of Chinese doctors’ job demands
Authors: Jin Weiqiong , Fang Yinghui , Zhang Yuchen , Lv Yijun
Published: May 2023

Objective

The purpose of this study was to develop a scale of clinician training elements in the new period and test its reliability and validity.

Methods

Our approach was based on interdisciplinary theory, systematology, collaborative innovation theory, and whole person education theory combined with the existing post competency model of Chinese doctors and the responsibilities and requirements endowed clinicians in the new historical period. The scale elements were extracted by referring to the relevant literature, and the training elements scale for clinicians in the new period were preliminarily formed. From July to August 2022, 1,086 clinicians from tertiary medical institutions in eastern, central, and western China were sampled and investigated. The questionnaire was revised via the critical ratio method and homogeneity test method, and the reliability and validity of the scale were also tested.

Results

The training elements scale for clinicians in the new period included the following eight dimensions: basic clinical knowledge, interdisciplinary knowledge, clinical skill operation, public health knowledge, technological innovation capability, lifelong learning needs, medical humanistic literacy, and international exchange vision, as well as 51 other items. The Cronbach’s α coefficient of the scale was 0.981, the half-reliability was 0.903, and the average variance extraction of each dimension was greater than 0.5. An exploratory factor analysis extracted eight main factors, and the cumulative variance contribution rate was 78.524%. Confirmatory factor analysis showed that the model fit was ideal and the factor structure was stable.

Conclusion

The clinician training factor scale in the new era can fully meet the current training needs of r clinicians, and has good reliability and validity. It can be widely used in medical colleges and universities as a reference to reform the content of medical training and education, and can also be used in the continuing education of clinicians after graduation to compensate for gaps in knowledge during clinical work.
Style and influencing factors of tutors-postgraduates’ interactions in Chinese medical colleges: a cross-sectional survey in Heilongjiang Province
Authors: Wang Mingsi , Wang Yanping , Fang Ming , Zhang Shue , Li Yilan , Cao Depin , Jin Yan
Published: May 2023

Objectives

This study assesses the style of tutor-postgraduate interactions in Chinese medical colleges and explores the association between postgraduates’ demographic factors and tutors’ demographic characteristics.

Methods

With the stratified sampling method, a cross-sectional online survey was used. A total of 813 medical postgraduates were recruited as participants, with an effective response rate of 85.49%. The two dimensions of “Professional Ability Interaction” and “Comprehensive Cultivation Interaction” in the self-developed “Instructor-Graduate Interaction Scale for Medical Colleges” were used as dependent variables. And tutors’ demographic characteristics and postgraduates’ demographic characteristics were taken as independent variables. Logistic regression analysis was used to explore the influencing factors of Tutor-Postgraduates Interactions in medical colleges.

Results

The Tutor-Postgraduates Interaction scale consists of 14 items from the two dimensions of “Professional Ability Interaction” and “Comprehensive Cultivation Interaction”. The results of the logistic regression analysis show the reasons for selecting the mentor students (industry recognition, the tutor’s research direction, charm in attracting mentors, and recommendations for mentor selection); student to mentor satisfaction; student to study life satisfaction; and regular academic seminars. Indirect guidance and a high postgraduate grade high are the protective factors of interaction between tutors and postgraduates of medical colleges and universities postgraduates. Older mentors and more graduate tutors are the risk factors for Tutor-Postgraduates Interaction in medical colleges (P < 0.05).

Conclusion

The current study proposes that managers should pay more attention to the double-track promotion of “Professional Ability Interaction” and “Comprehensive Cultivation Interaction”. We should not only pay attention to the cultivation of postgraduates’ professional ability but also pay more attention to the comprehensive cultivation including postgraduates’ mental and psychological aspects. The interaction between tutors and postgraduates in medical colleges is generally good, but much attention should be given to the dual-track promotion mentioned above. Regular academic seminars play an important role in the process of postgraduate training. The research findings, including the influencing factors regarding tutor-postgraduate interactions, the Professional Ability Interaction and Comprehensive Cultivation Interaction, are very informative and can contribute to strategies for postgraduate management systems that enhance this relationship.
Defining ready for discharge from sub-acute care: a qualitative exploration from multiple stakeholder perspectives
Authors: Gledhill Kate , Bucknall Tracey K , Lannin Natasha A , Hanna Lisa
Published: May 2023

Background

Planning discharges from subacute care facilities is becoming increasingly complex due to an ageing population and a high demand on services. The use of non-standardised assessments to determine a patient’s readiness for discharge places a heavy reliance on a clinician’s judgement which can be influenced by system pressures, past experiences and team dynamics. The current literature focusses heavily on discharge-readiness from clinicians’ perspectives and in the acute care setting. This paper aimed to explore the perceptions of discharge-readiness from the perspectives of key stakeholders in subacute care: inpatients, family members, clinicians and managers.

Methods

A qualitative descriptive study was conducted, exploring the views of inpatients (n = 16), family members (n = 16), clinicians (n = 17) and managers (n = 12). Participants with cognitive deficits and those who did not speak English were excluded from this study. Semi-structured interviews and focus groups were conducted and audio-recorded. Following transcription, inductive thematic analysis was completed.

Results

Participants identified that there are both patient-related and environmental factors that influence discharge-readiness. Patient-related factors discussed included continence, functional mobility, cognition, pain and medication management skills. Environmental factors centred around the discharge (home) environment, and were suggested to include a safe physical environment alongside a robust social environment which was suggested to assist to fill any gaps in functional capabilities (i.e. patient-related factors).

Conclusions

These findings make a unique contribution to the literature by providing a thorough exploration of determining discharge-readiness as a combined narrative from the perspectives from key stakeholders. Findings from this qualitative study identified key personal and environmental factors influencing patients’ discharge-readiness, which may allow health services to streamline the determination of discharge-readiness from subacute care. Understanding how these factors might be assessed within a discharge pathway warrants further attention.
Low agreement among patients and clinicians about urgency and safety to wait for assessment in primary care after hours medical care: results of cross-sectional matched surveys
Authors: Barnes Katelyn , Arpel Caitlin , Douglas Kirsty
Published: May 2023

Background

Discordance between patient and clinician perceived urgency may drive “inappropriate” presentations to after-hours medical services. This paper investigates the level of agreement between patient and clinicians’ perceptions of urgency and safety to wait for an assessment at after-hours primary care services in the ACT.

Methods

Cross-sectional survey voluntarily completed by patients and then clinicians at after-hours medical services in May/June, 2019. Agreement between patients and clinicians is measured by Fleiss kappa. Agreement is presented overall, within specific categories of urgency and safety to wait, and by after-hours service type.

Results

888 matched records were available from the dataset. Overall inter-observer agreement between patients and clinicians on the urgency of presentations was slight (Fleiss kappa = 0.166; 95% CI 0.117–0.215, p < 0.001). Agreement within specific ratings of urgency ranged from very poor to fair. Overall inter-rater agreement on how long it would be safe to wait for assessment was fair (Fleiss kappa = 0.209; 95% CI 0.165–0.253, p < 0.001). Agreement within specific ratings ranged from poor to fair. By site type, agreement between patients and clinicians on urgency ranged from not significant to fair and agreement for safety to wait ranged from very poor to slight. Agreement on urgency of issue was more often reported among patients attending their usual health service or seeing their usual clinician compared to patients attending an unfamiliar health service or clinician (χ2(1) = 7.283, p = 0.007 and χ2(1) = 16.268, p < 0.001, respectively).

Conclusions

Low levels of agreement between patients and clinicians on perceived urgency and safety to wait for issues to be assessed indicate potential inefficiency in primary care use after-hours. Agreement on urgency of issues was more common among patients attending a familiar health service or familiar clinician. Improving health literacy, particularly health system literacy, and supporting continuity of care may help to support patients to engage with the most appropriate level of care at the most appropriate time.
Molecular mechanism of engineered Zymomonas mobilis to furfural and acetic acid stress
Authors: Shabbir Samina , Wang Weiting , Nawaz Mohsin , Boruah Prerona , Kulyar Muhammad Fakhar-e-Alam , Chen Mao , Wu Bo , Liu Panting , Dai Yonghua , Sun Lingling , Gou Qiyu , Liu Renbin , Hu Guoquan , Younis Tahira , He Mingxiong
Published: May 2023

Acetic acid and furfural (AF) are two major inhibitors of microorganisms during lignocellulosic ethanol production. In our previous study, we successfully engineered Zymomonas mobilis 532 (ZM532) strain by genome shuffling, but the molecular mechanisms of tolerance to inhibitors were still unknown. Therefore, this study investigated the responses of ZM532 and its wild-type Z. mobilis (ZM4) to AF using multi-omics approaches (transcriptomics, genomics, and label free quantitative proteomics). Based on RNA-Seq data, two differentially expressed genes, ZMO_RS02740 (up-regulated) and ZMO_RS06525 (down-regulated) were knocked out and over-expressed through CRISPR-Cas technology to investigate their roles in AF tolerance. Overall, we identified 1865 and 14 novel DEGs in ZM532 and wild-type ZM4. In contrast, 1532 proteins were identified in ZM532 and wild-type ZM4. Among these, we found 96 important genes in ZM532 involving acid resistance mechanisms and survival rates against stressors. Furthermore, our knockout results demonstrated that growth activity and glucose consumption of mutant strains ZM532∆ZMO_RS02740 and ZM4∆ZMO_RS02740 decreased with increased fermentation time from 42 to 55 h and ethanol production up to 58% in ZM532 than that in ZM532∆ZMO_RS02740. Hence, these findings suggest ZMO_RS02740 as a protective strategy for ZM ethanol production under stressful conditions.
Coverage of intermittent preventive treatment of malaria in infants after four years of implementation in Sierra Leone
Authors: Fombah Augustin E. , Chen Haily , Owusu-Kyei Kwabena , Quinto Llorenç , Gonzalez Raquel , Williams Julian , Berne Mireia LLach , Wassenaar Myrte , Jalloh Abubakarr , Sunders Joe-Henry C. , Ramirez Maximo , Bertran-Cobo Cesc , Saute Francisco , Ekouevi Didier K. , Briand Valérie , Kamara Anitta R. Y. , Sesay Tom , Samai Mohamed , Menendez Clara
Published: May 2023

Background

Intermittent Preventive Treatment of malaria in infants (IPTi) is a malaria control strategy consisting of the administration of an anti-malarial drug alongside routine immunizations. So far, this is being implemented nationwide in Sierra Leone only. IPTi has been renamed as Perennial Malaria Chemoprevention -PMC-, accounting for its recently recommended expansion into the second year of life. Before starting a pilot implementation on PMC, the currently implemented strategy and malaria prevalence were assessed in young children in selected areas of Sierra Leone.

Methods

A cross-sectional, community-based, multi-stage cluster household survey was conducted from November to December 2021 in selected districts of the Northern and northwestern provinces of Sierra Leone among 10–23 months old children, whose caretakers gave written informed consent to participate in the survey. Coverage of IPTi and malaria prevalence—assessed with rapid diagnostic tests—were calculated using percentages and 95% confidence intervals weighted for the sampling design and adjusted for non-response within clusters. Factors associated with RDT + and iPTi coverage were also assessed.

Results

A total of 720 children were recruited. Coverage of three IPTi doses was 50.57% (368/707; 95% CI 45.38–55.75), while prevalence of malaria infection was 28.19% (95% CI 24.81–31.84). Most children had received IPTi1 (80.26%, 574/707; 95% CI 75.30–84.44), and IPTi2 (80.09%, 577/707; 95% CI 76.30–83.40) and over half of the children also received IPTi3 (57.72%, 420/707; 95% CI 53.20–62.11). The uptake of each IPTi dose was lower than that of the vaccines administered at the same timepoint at all contacts.

Conclusion

In Sierra Leone, half of the children received the three recommended doses of IPTi indicating an increase in its uptake compared to previous data of just a third of children receiving the intervention. However, efforts need to be made in improving IPTi coverage, especially in the planned expansion of the strategy into the second year of life following recent WHO guidelines.
Water bath is more efficient than hot air oven at thermal inactivation of coronavirus
Authors: Gu Xinxia , Cao Ting , Mou Jun , Liu Jie
Published: May 2023

Background

Thermal inactivation is a conventional and effective method of eliminating the infectivity of pathogens from specimens in clinical and biological laboratories, and reducing the risk of occupational exposure and environmental contamination. During the COVID-19 pandemic, specimens from patients and potentially infected individuals were heat treated and processed under BSL-2 conditions in a safe, cost-effective, and timely manner. The temperature and duration of heat treatment are optimized and standardized in the protocol according to the susceptibility of the pathogen and the impact on the integrity of the specimens, but the heating device is often undefined. Devices and medium transferring the thermal energy vary in heating rate, specific heat capacity, and conductivity, resulting in variations in efficiency and inactivation outcome that may compromise biosafety and downstream biological assays.

Methods

We evaluated the water bath and hot air oven in terms of pathogen inactivation efficiency, which are the most commonly used inactivation devices in hospitals and biological laboratories. By evaluating the temperature equilibrium and viral titer elimination under various conditions, we studied the devices and their inactivation outcomes under identical treatment protocol, and to analyzed the factors, such as energy conductivity, specific heat capacity, and heating rate, underlying the inactivation efficiencies.

Results

We compared thermal inactivation of coronavirus using different devices, and have found that the water bath was more efficient at reducing infectivity, with higher heat transfer and thermal equilibration than a forced hot air oven. In addition to the efficiency, the water bath showed relative consistency in temperature equilibration of samples of different volumes, reduced the need for prolonged heating, and eliminated the risk of pathogen spread by forced airflow.

Conclusions

Our data support the proposal to define the heating device in the thermal inactivation protocol and in the specimen management policy.
Location and condition based reconstruction of colon cancer microbiome from human RNA sequencing data
Authors: Sambruni Gaia , Macandog Angeli D. , Wirbel Jakob , Cagnina Danilo , Catozzi Carlotta , Dallavilla Tiziano , Borgo Francesca , Fazio Nicola , Fumagalli-Romario Uberto , Petz Wanda L. , Manzo Teresa , Ravenda Simona P. , Zeller Georg , Nezi Luigi , Schaefer Martin H.
Published: May 2023

Background

The association between microbes and cancer has been reported repeatedly; however, it is not clear if molecular tumour properties are connected to specific microbial colonisation patterns. This is due mainly to the current technical and analytical strategy limitations to characterise tumour-associated bacteria.

Methods

Here, we propose an approach to detect bacterial signals in human RNA sequencing data and associate them with the clinical and molecular properties of the tumours. The method was tested on public datasets from The Cancer Genome Atlas, and its accuracy was assessed on a new cohort of colorectal cancer patients.

Results

Our analysis shows that intratumoural microbiome composition is correlated with survival, anatomic location, microsatellite instability, consensus molecular subtype and immune cell infiltration in colon tumours. In particular, we findFaecalibacterium prausnitzii,Coprococcus comes,Bacteroidesspp.,Fusobacteriumspp. andClostridiumspp. to be strongly associated with tumour properties.

Conclusions

We implemented an approach to concurrently analyse clinical and molecular properties of the tumour as well as the composition of the associated microbiome. Our results may improve patient stratification and pave the path for mechanistic studies on microbiota-tumour crosstalk.
Genomic and transcriptomic features between primary and paired metastatic fumarate hydratase–deficient renal cell carcinoma
Authors: Liang Jiayu , Sun Guangxi , Pan Xiuyi , Zhang Mengni , Shen Pengfei , Zhu Sha , Zhao Jinge , Zheng Linmao , Zhao Junjie , Chen Yuntian , Yin Xiaoxue , Chen Junru , Hu Xu , Zeng Yuhao , Chen Jianhui , Wang Yongquan , Liu Zhihong , Yao Jin , Su Minggang , Huang Rui , Liao Banghua , Wei Qiang , Li Xiang , Zhou Qiao , Liu Jiyan , Shen Yali , Liu Zhenhua , Chen Ni , Zeng Hao , Zhang Xingming
Published: May 2023

Background

Fumarate hydratase–deficient renal cell carcinoma (FH-RCC) is a rare highly aggressive subtype of kidney cancer for which the distinct genomic, transcriptomic, and evolutionary relationships between metastatic and primary lesions are still unclear.

Methods

In this study, whole-exome, RNA-seq, and DNA methylation sequencing were performed on primary-metastatic paired specimens from 19 FH-RCC cases, including 23 primary and 35 matched metastatic lesions. Phylogenetic and clonal evolutionary analyses were used to investigate the evolutionary characteristics of FH-RCC. Transcriptomic analyses, immunohistochemistry, and multiple immunofluorescence experiments were performed to identify the tumor microenvironmental features of metastatic lesions.

Results

Paired primary and metastatic lesions generally showed similar characteristics of tumor mutation burden, tumor neoantigen burden, microsatellite instability score, CNV burden, and genome instability index. Notably, we identified an FH-mutated founding MRCA (the most recent common ancestor) clone that dominated the early evolutionary trajectories in FH-RCC. Although both primary and metastatic lesions manifested high immunogenicity, metastatic lesions exhibited higher enrichment of T effector cells and immune-related chemokines, together with upregulation of PD-L1, TIGIT, and BTLA. In addition, we found that concurrentNF2mutation may be associated with bone metastasis and upregulation of cell cycle signature in metastatic lesions. Furthermore, although in FH-RCC metastatic lesions in general shared similar CpG island methylator phenotype with primary lesions, we found metastatic lesions displaying hypomethylated chemokine and immune checkpoints related genomic loci.

Conclusions

Overall, our study demonstrated the genomic, epigenomic, and transcriptomic features of metastatic lesions in FH-RCC and revealed their early evolutionary trajectory. These results provided multi-omics evidence portraying the progression of FH-RCC.
Primary hepatic Epstein–Barr virus-positive diffuse large B-cell lymphoma associated with azathioprine immunosuppression: a case report
Authors: Marell Paulina S. , Shi Min , Wingo Majken T.
Published: May 2023

Background

Hepatic masses are relatively common findings, and the diagnostic approach often begins by identifying patient and mass characteristics that are risk factors for malignancy. Chronic immunosuppression is a known risk factor for various malignancies, and azathioprine in particular has been reported in association with solid and hematologic malignancies, including diffuse large B-cell lymphoma.

Case presentation

A 46-year-old white woman presented to clinic with several weeks of gastrointestinal symptoms and was found to have a hepatic mass on imaging. Her history was notable for neuromyelitis optica spectrum disorder on chronic immunosuppression with azathioprine. It was initially thought to be an inflammatory adenoma. On 6-month follow-up imaging, the mass had grown rapidly in size and was surgically resected. Further workup determined the mass to be an iatrogenic immunodeficiency-associated Epstein–Barr virus-positive diffuse large B-cell lymphoma confined to the liver. Azathioprine was discontinued and the patient underwent treatment with rituximab with no evidence of recurrence 2 years after the initiation of treatment.

Conclusions

This case report describes the first time hepatic Epstein–Barr virus-positive diffuse large B-cell lymphoma has been reported with azathioprine, which highlights the unique sequelae of chronic immunosuppression, including atypical hematologic malignancies, and the importance of considering chronic immunosuppression in the diagnostic evaluation of a hepatic mass.
Perspective: lessons learned from the COVID-19 pandemic concerning the resilience of the population
Authors: Adini Bruria , Kimhi Shaul
Published: May 2023

Background

A vital stakeholder in the successful management of the COVID-19 pandemic is the public. The degree of involvement of the population in managing the pandemic, and the leadership perception of the public, had a direct impact on the resilience of the population and level of adherence to the issued protective measures.

Main body

Resilience refers to the ability to ‘bounce back’ or ‘bounce forward’ following adversity. Resilience facilitates community engagement which is a crucial component of combating the COVID-19 pandemic. The article highlights six insights recognized in studies conducted in Israel during and following the pandemic concerning the resilience of the country’s population. (1) Contrary to varied adversities in which the community serves as an important support system to the individuals, this type of support was substantially impaired during the COVID-19 pandemic, due to the need to maintain isolation, social distancing, and lockdowns. (2) Policy-making during the pandemic should be based on evidence-based data, rather than on assumptions made by decision-makers. This gap led the authorities during the pandemic to adopt measures that were ineffective, such as risk communication based on ‘scare tactics’ concerning the virus, when the highest risk perceived by the public was political instability. (3) Societal resilience is associated with the public’s behavior, such as with vaccine hesitancy and uptake. (4) Factors that affect the levels of resilience include, among others, self-efficacy (impacts individual resilience); social, institutional, and economic aspects as well as well-being (impact community resilience); and hope and trust in the leadership (impact societal resilience). (5) The public should be perceived as an asset in managing the pandemic, thus becoming a vital part of the ‘solution’. This will lead to a better understanding of the needs and expectations of the population and an applicable ‘tailoring’ of the messages that address the public. (6) The gap between science and policymaking must be bridged, to achieve optimal management of the pandemic.

Conclusions

Improving preparedness for future pandemics should be based on a holistic view of all stakeholders, including the public as a valued partner, connectivity between policymakers and scientists, and strengthening the public’s resilience, by enhancing trust in authorities.
Breastfeeding support provided by lactation consultants in high-income countries for improved breastfeeding rates, self-efficacy, and infant growth: a systematic review and meta-analysis protocol
Authors: D’Hollander Curtis J. , McCredie Victoria A. , Uleryk Elizabeth M. , Keown-Stoneman Charles D. G. , Birken Catherine S. , O’Connor Deborah L. , Maguire Jonathon L.
Published: May 2023

Background

It is well established that breast milk offers numerous health benefits for mother and child. Mothers are recommended to exclusively breastfeed their child until 6 months of age, with continued breastfeeding up to 1–2 years of age or beyond. Yet, these recommendations are met less than half of the time in high-income countries. Lactation consultants specialize in supporting mothers with breastfeeding and are a promising approach to improving breastfeeding rates. For lactation consultant interventions to be implemented widely as part of public health policy, a better understanding of their effect on breastfeeding rates and important health outcomes is needed.

Methods

The overall aim of this systematic review is to evaluate the effect of lactation consultant interventions provided to women, compared to usual care, on breastfeeding rates (primary outcome), maternal breastfeeding self-efficacy, and infant growth. A search strategy has been developed to identify randomized controlled trials published in any language between 1985 and April 2023 in CENTRAL, MEDLINE, EMBASE, CINAHL, Scopus, and Web of Science. We will also perform a search of the grey literature and reference lists of relevant studies and reviews. Two reviewers will independently extract data on study design, baseline characteristics, details of the interventions employed, and primary and secondary outcomes using a pre-piloted standardized data extraction form. Risk of bias and quality of evidence assessment will be done independently and in duplicate using the Cochrane Risk of Bias tool and GRADE approach, respectively. Where possible, meta-analysis using random-effects models will be performed, otherwise a qualitative summary will be provided. We will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Discussion

This review will fill an important gap in the lactation support literature. The findings will be of importance to policymakers who seek to implement interventions to improve breastfeeding rates.

Trial registration

This review has been registered in the PROSPERO database (ID: CRD42022326597).
Controlled g-frames and dual g-frames in Hilbert spaces
Authors: Liu Hui-Min , Fu Yan-Ling , Tian Yu
Published: May 2023

As generalizations of g-frames and controlled frames, the theory of controlled g-frames has been deeply studied. This paper addresses the controlled g-frames and dual g-frames in Hilbert spaces. We first present some equivalent characterizations of controlled g-frames. Then, we introduce the concepts of controlled dual g-frames and controlled dual g-frames operator, get some properties of them. Finally, we obtain some characterizations of the controlled dual g-frames for a given controlled g-frame by the method of operator theory.
Persistence properties and blow-up phenomena for a generalized Camassa–Holm equation
Authors: Wang Ying , Guo Yunxi
Published: May 2023

In this paper, we investigate a generalized Camassa–Holm equation. Firstly, we establish the persistence properties of strong solutions for the equation in weighted spaces $L^{p}_{\phi}=L^{p}(\mathbb{R},\phi ^{p}\,dx)$

L
ϕ
p

=

L
p

(
R
,

ϕ
p

d
x
)
. Then we present some sufficient conditions of blow-up solutions assuming that the initial data satisfy certain conditions, which are more precise than those in the previous work.
NOTCH2NLC GGC repeat expansion causes retinal pathology with intranuclear inclusions throughout the retina and causes visual impairment
Authors: Sone Jun , Ueno Shinji , Akagi Akio , Miyahara Hiroaki , Tamai Chisato , Riku Yuichi , Yabata Hiroyuki , Koizumi Ryuichi , Hattori Tomohiro , Hirose Hiroshi , Koyanagi Yoshito , Kobayashi Rei , Okada Hisashi , Kishimoto Yoshiyuki , Hashizume Yoshio , Sobue Gen , Yoshida Mari , Iwasaki Yasushi
Published: May 2023

The retinal pathology of genetically confirmed neuronal intranuclear inclusion disease (NIID) is yet unknown. We report the ocular findings in four NIID patients with NOTCH2NLC GGC repeat expansion to investigate the pathology of retinopathy. All four NIID patients were diagnosed by skin biopsy and NOTCH2NLC GGC repeat analysis. Ocular findings in patients with NIID were studied using fundus photographs, optical coherence tomographic images (OCT), and full-field electroretinograms (ERGs). The histopathology of the retina was studied on autopsy samples from two cases with immunohistochemistry. All patients had an expansion of the GGC repeat (87–134 repeats) in the NOTCH2NLC. Two patients were legally blind and had been diagnosed with retinitis pigmentosa prior to the diagnosis of NIID and assessed with whole exome sequencing to rule out comorbidity with other retinal diseases. Fundus photographs around the posterior pole showed chorioretinal atrophy in the peripapillary regions. OCT showed thinning of the retina. ERGs showed various abnormalities in cases. The histopathology of autopsy samples showed diffusely scattered intranuclear inclusions throughout the retina from the retinal pigment epithelium to the ganglion cell layer, and optic nerve glial cells. And severe gliosis was observed in retina and optic nerve. The NOTCH2NLC GGC repeat expansion causes numerous intranuclear inclusions in the retina and optic nerve cells and gliosis. Visual dysfunction could be the first sign of NIID. We should consider NIID as one of the causes of retinal dystrophy and investigate the GGC repeat expansion in NOTCH2NLC.
Blockchain-oriented approach for detecting cyber-attack transactions
Authors: Feng Zhiqi , Li Yongli , Ma Xiaochen
Published: May 2023

With the high-speed development of decentralized applications, account-based blockchain platforms have become a hotbed of various financial scams and hacks due to their anonymity and high financial value. Financial security has become a top priority with the sustainable development of blockchain-based platforms because of an increasing number of cyber attacks, which have resulted in a huge loss of crypto assets in recent years. Therefore, it is imperative to study the real-time detection of cyber attacks to facilitate effective supervision and regulation. To this end, this paper proposes the weighted and extended isolation forest algorithms and designs a novel framework for the real-time detection of cyber-attack transactions by thoroughly studying and summarizing real-world examples. Furthermore, this study develops a new detection approach for locating the compromised address of a cyber attack to resolve the data scarcity of hack addresses and reduce time consumption. Moreover, three experiments are carried out not only to apply on different types of cyber attacks but also to compare the proposed approach with the widely used existing methods. The results demonstrate the high efficiency and generality of the proposed approach. Finally, the lower time consumption and robustness of our method were validated through additional experiments. In conclusion, the proposed blockchain-oriented approach in this study can handle real-time detection of cyber attacks and has significant scope for applications.
Social–financial approach for analyzing financial transitions
Authors: Wu Xifeng , Shen Yue , Chen Jin , Chen Yu
Published: May 2023

This study proposes a social-financial approach (SFA) to fill the methodological research gap in strategic policy design for managing financial transitions during social changes. The SFA seeks to characterize inclusive transitions in response to innovation and analyze financial management in social changes. Using a multilevel perspective, we combine evolutionary finance and inclusive growth analytics into this framework. We contend that the interaction between the different levels can be summarized as spontaneous adjustments and the alignment of financial elements with the indicators. Actors who attempt to achieve their goals based on past performance evaluations and other forms of bounded rationality strive to cope with adjustments and further trigger a reorientation of the existing regime. We also developed a new configuration tool called the three-axis description to describe the evolution of financial transitions at different stages. These methods allow us to analyze the evolution of financial transition and efficiency, and we argue that market efficiency evolves in stages with the financial transition. Finally, to demonstrate the capability of SFA to identify diverse financial transition pathways, we examined an example case: the establishment of the Bretton Woods System.
The role of English and the sociocultural structure of Bahasa: a study of Brunei Darussalam
Authors: Morve Roshan K. , Wen Xu , Mansour Nasser
Published: May 2023

This paper looks at the role of English in Brunei and the sociocultural structure of Bahasa/language in Brunei Darussalam. The aim of this research is to critically analyse sociocultural theory from Vygotsky’s “peak psychology” approach and understand depth-knowledge of sociocultural theory from other scholars’ perspectives. The scholars’ views on education, language and sociocultural importance-related topics have been analysed by Barry, Goode, Jones, Haji-Othman, Sharbawi and Gardiner. These scholars’ ideas give a better understanding of the sociocultural importance of Bruneian’s individual development. For this research, a qualitative method applies and collected data is critically analysed in detail. This research has the potential to discuss the link between language evolution and Bruneian sociocultural development. The “Citizenship Acts 1961” is relevant to discuss the theoretical concepts like, ‘nationality’ and ‘ethnic identification’ from the Bruneian context. To put it in a nutshell, the ratification of “Melayu Islam Beraja” or “Malay Islamic Monarchy” and the impact of linguistic diversity in Brunei consist of a Bruneian identity. In bilingual education policy, Bahasa Melayu and English have a major role in the child development. Although a balance of regional languages and English is essential to maintain the “Bruneian” identity. Brunei is a small country but it is diverse, multilingual and multicultural.
Beyond ‘race’?: a rejoinder
Authors: Scharrer Tabea , Saharso Sawitri
Published: May 2023

In this rejoinder we argue, based on the papers of this commentary series, that ‘race’ is such a tricky notion because it can be used in (at least) two very different and contradictory ways—as a concept to disentangle racism and racialisation (what M’charek calls the ‘work race actually does’) and as a way of categorization and social classification, in which case it might create the very essentialised hierarchies ‘race’ as a critical concept tries to disentangle. We wonder if it is indeed possible to use ‘race’ as a concept without evoking ‘race’ as a social classification. At first, we give a short summary of the four discussion papers and then delve into two aspects the papers share, namely the need for spatial and temporal contextualization and comparison, as well as their choice not to take up our invitation to compare race as a category with gender. In a second step we will discuss two points arising from the papers, (1) ‘race’ as category, not as lens, often resulting in essentialism and (2) ‘race’ as potentially obscuring racism and racialisation. We conclude by proposing to give more space to complexity.