bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification on surrogating overall survival with progression-free survival of first-line immunochemotherapy in advanced esophageal squamous cell carcinoma—an exploration of surrogate endpoint
Authors: Zhang Zewei , Xie Chunxia , Gao Tiantian , Yang Yuxian , Yang Yong , Zhao Lei
Published: February 2023

Background

Overall survival (OS) is the gold standard to assess novel therapeutics to treat cancer. However, to identify early efficacy and speed up drug approval, trials have used progression-free survival (PFS) as a surrogate endpoint (SE). Herein, we aimed to examine if PFS could function as an OS surrogate in advanced Esophageal Squamous Cell Carcinoma (ESCC) treated with first-line immunochemotherapy.

Methods

Two hundred ninety-two advanced ESCC patients treated using inhibitors of PD-1/PD-L1 + chemotherapy or chemotherapy alone were collected. In addition, six phase III randomized clinical trials were eligible for inclusion. Bayesian normal-induced-copula-estimation model in retrospective patient data and regression analysis in the published trial data were used to determine the PFS-OS correlation.

Results

PFS correlated moderately with OS in the retrospective cohort (Kendall’s Tau = 0.684, τ = 0.436). In trial-level, treatments effects for PFS correlated weakly with those for OS in intention-to-treat population (R2 = 0.436, adj.R2 = 0.249, P > 0.05) and in PD-L1-enriched population (R2 = 0.072). In arm-level, median PFS also correlated weakly with median OS. Moreover, analysis of the retrospective cohort demonstrated that the annual death risk after progression in the continued immunotherapy group was considerably lower than that in the discontinued group.

Conclusion

In trials of anti-PD-1 agents to treat advanced ESCC, the current results provide only weak support for PFS as an OS surrogate; OS cannot be substituted completely by PFS in these cases. The results also suggest that qualified patients with advanced ESCC might benefit from continuous immunotherapy beyond progression to achieve a decreased risk of death.
Hypo vs. hyperthyroid eye disease: is there any difference?
Authors: Eshraghi Bahram , Pourazizi Mohsen , Abbasi Maryam , Mohammadbeigy Iman
Published: February 2023

Background

Thyroid-eye disease (TED) is the most common extra-thyroidal presentation of graves’ disease. We performed this study to compare clinical characteristics of TED in hypothyroid vs. hyperthyroid patients.

Methods

This was a retrospective analytical cross-sectional study in which we compared demographics, severity (EUGOGO classification) and activity (clinical activity score) of TED, thyroid disease duration, TED duration and clinical signs between hypothyroid eye disease (Ho-TED) and hyperthyroid eye disease (Hr-TED). To minimize the effect of selection bias and potential confounders, 1:1 propensity score matching (PSM) was also performed.

Results

Three hundred and seventy-four patients (341 Hr-TED and 33 Ho-TED) with a female to male ratio of 1.4:1 were identified in our study. Female to male ratio was 1.3:1 in hyperthyroid and 4.5:1 in hypothyroid group (P = 0.005). The duration of thyroid disease was longer in Ho-TED (P = 0.002) while the duration of eye disease was not significantly different between the Hr-TED (mean = 24.33 ± 41.69, median = 8) and Ho-TED (mean = 19.06 ± 33.60, median = 12) (P = 0.923). Most of the patients in hypothyroid group developed eye involvement after thyroid disease (80.0% in hypo vs. 48.1% in hyper, P = 0.003). Severity (P = 0.13) and activity (P = 0.11) was not different between Hr-TED and Ho-TED patients. After PSM analysis, no clinical characteristics were significantly different between the two groups (P > 0.05).

Conclusion

The results of our study showed several differences between the Hr/Ho TED patients including sex, duration of thyroid disease and pattern of eye involvement. After matching the two groups with statistical methods, no clinical characteristics were different between Hr-TED and Ho-TED patients.
Iranian school-aged twin registry: preliminary reports and project progress
Authors: Abtahi Hamidreza , Gholamzadeh Marsa , Baharii Roza
Published: February 2023

Background

National Persian school-aged twin registry was established to provide a platform for twin studies. In this report, we describe defining registry characteristics, database design, and preliminary results regarding gathered data in the first phase of the registry program.

Method

Through focus group discussions, the required data elements to design the database and data collection process were defined. First, a list of twins in school-aged groups was retrieved from the electronic database of the Ministry of Education. Tehran schools were selected for the first phase of our registry. Standard “Pea-in-Pods” questionnaire and twins’ similarity questionnaires were filled out by the parents themselves in addition to demographic information. Data were analyzed using SPSS v.22.

Results

The first national school-aged twin registry was established in 2018. Firstly, the required data sets and data collection process were defined using focus group discussions. At the country level, the initial information on 189,738 students was retrieved from the national database of the Ministry of Education. They were born between 2003 and 2017, of which 94,997 are boys (50.1%) and 94,741 are girls (49.9%). Of them, a total of 5,642 pairs of school-aged twins participated in the first phase of our program. Our sample size comprised 9772 twins, 906 triples, and 92 quadruplets. The analysis of the zygosity questionnaire showed that 14% of twin pairs were identified as monozygotic twins.

Conclusion

Recruiting school-aged twins through school health assistants leads to high enrollment and decreasing costs for the twin registry. The study showed a high rate of dizygotic twins that need to be verified by twin bio-sample in the next phase of studies.
Cohort Profile: Real-Time Insights of COVID-19 in India (RTI COVID-India)
Authors: Banerjee Joyita , Petrosyan Sarah , Rao Abhijith R. , Jacob Steffi , Khobragade Pranali Yogiraj , Weerman Bas , Chien Sandy , Angrisani Marco , Agarwal Arunika , Madan Nirupam , Sethi Tanya , Dey Sharmistha , Schaner Simone , Bloom David E. , Lee Jinkook , Dey A. B.
Published: February 2023

Background

The coronavirus disease (COVID) pandemic caused disruption globally and was particularly distressing in low- and middle-income countries such as India. This study aimed to provide population representative estimates of COVID-related outcomes in India over time and characterize how COVID-related changes and impacts differ by key socioeconomic groups across the life course.

Methods

The sample was leveraged from an existing nationally representative study on cognition and dementia in India: Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD). The wave-1 of LASI-DAD enrolled 4096 older adults aged 60 years and older in 3316 households from 18 states and union territories of India. Out of the 3316 LASI-DAD households, 2704 with valid phone numbers were contacted and invited to participate in the Real-Time Insights COVID-19 in India (RTI COVID-India) study. RTI COVID-India was a bi-monthly phone survey that provided insight into the individual’s knowledge, attitudes, and behaviour towards COVID-19 and changes in the household’s economic and health conditions throughout the pandemic. The survey was started in May 2020 and 9 rounds of data have been collected.

Findings till date

Out of the 2704 LASI-DAD households with valid phone numbers, 1766 households participated in the RTI COVID-India survey at least once. Participants were in the age range of 18–102 years, 49% were female, 66% resided in rural area. Across all rounds, there was a higher report of infection among respondents aged 60–69 years. There was a greater prevalence of COVID-19 diagnosis reported in urban (23.0%) compared to rural areas (9.8%). Respondents with higher education had a greater prevalence of COVID-19 diagnosis compared to those with lower or no formal education. Highest prevalence of COVID-19 diagnosis was reported from high economic status compared to middle and low economic status households. Comparing education gradients in experiencing COVID-19 symptoms and being diagnosed, we observe an opposite pattern: respondents with no formal schooling reported the highest level of experiencing COVID-19 symptoms, whereas the greatest proportion of the respondents with secondary school or higher education reported being diagnosed with COVID-19.

Future plans

The study group will analyse the data collected showing the real-time changes throughout the pandemic and will make the data widely available for researchers to conduct further studies.
Environmental health aspects and microbial infections of the recreational water
Authors: Hassanein Faika , Masoud Inas M. , Fekry Marwa M. , Abdel-Latif Mohamed S. , Abdel-Salam Hussein , Salem Mohamed , Shehata Amany I
Published: February 2023

Background

Swimming pools are places for practicing sports, recreation, relaxation, and socialization. However, swimming pools can expose swimmers to physicochemical and microbiological risks. Accordingly, we studied the environmental health aspects and microbial infections for such recreational water aiming to disclose the possible risks they pose on swimmers.

Methods

26 pools in Alexandria, Egypt were checked for water quality; 13 pools were checked in winter then summer, and other 13 pools were checked in summer only. Water was collected from both the top and the bottom of each pool; a total of 78 samples were collected in sterile containers. Each sample was divided into three parts; the first part was used for assessing the bacteriological quality of water. They were tested for total colony count (TCC), total coliform (TC), fecal coliform, and E. coli. The second part was used for chemical analysis. The third part was checked for parasitological study.

Results

Obtained data showed that only 7.7%, 78.2%, and 100% of the examined water samples have been found to fulfill the Egyptian standards for TCC, TC, and E. coli, respectively. Moreover, parasitic infection (PI) was noticed in 73.1% of the collected water samples; mainly Cyclospra and Isospora (37.2% each), followed by Cryptosporidium spp., Giradia lamblia, Microsporidia spp., and Blastocystis spp. (34.6%, 21.8%, 15.4%, and 14.1%, respectively). Acanthameba spp. was detected but at a lower rate (5.1%). The frequency of cleaning the swimming pools, flow rate, Cl2, and total dissolved solids are significantly affected PI, independently.

Conclusion

The tested water samples don’t meet Egyptian bacteriological criteria. High parasitic contamination despite high residual chlorine level mainly intestinal coccidia, G. lamblia, microsporidia, and Blastocystis spp. Thus, monitoring pool’s water quality and improving the disinfection system are mandatory. Consequently, Health education regarding hygienic behaviors before and during swimming should be included in governmental programs.
Trends of completed suicide rates among Malaysian elderly between 1995 and 2020
Authors: Abu Bakar Nurul Salwana , Zainuddin Nur Azmiah , Seman Zamtira , Khamal Noor Raihan , Ismail Masrol Hafizal
Published: February 2023

Background

Suicide among the elderly has become a global public health concern. This study was carried out to determine the trend of completed suicide rates according to age, sex, and ethnicity and the suicidal methods among the elderly in Malaysia.

Methods

All suicide-related deaths in elderly aged 60 years and above from the Year 1995 to 2020 reported to the National Registration Department (NRD) were analyzed. Causes of death for suicide were coded based on the International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10). The completed suicide rate was calculated by dividing the completed suicide number by the total elderly population for the respective year.

Results

Overall, the analysis of 1,600 suicide-related deaths was investigated over 26 years. Male was seen to be correlated with higher suicidal risk, with a male–female relative risk (RR) = 1.89 (95%CI:1.46,2.45). The risk of suicide was also found to be significantly higher for those aged 60 to 74 years old and Chinese, with RR = 4.26 (95%CI:2.94, 6.18) and RR = 5.81 (95%CI: 3.70, 9.12), respectively. Hanging was found to be a statistically significant suicide method (IRR:4.76, 95%CI:2.34,9.65) as compared to pesticide poisoning. The completed suicide rate was fluctuating over the years.

Conclusions

In conclusion, it is believed that Malaysia's elderly suicide rate has reached an alarmingly high incidence. By identifying the crucial criteria of sociodemographic factors, the government and responsible agencies have the essential and additional information to put together a more effective strategy and approach to overcome the issue in the future.
Construct validity and internal consistency of the Home and Family Work Roles Questionnaires: a cross-sectional study with exploratory factor analysis
Authors: Dabbagh A. , Seens H. , Fraser J. , MacDermid J. C.
Published: February 2023

Introduction

Exploratory Factor Analysis (EFA) measures the underlying relationships between questionnaire items and the factors (“constructs”) measured by a questionnaire. The Home and Family Work Roles Questionnaire has not been assessed using EFA; therefore, our objective was to identify the factors measured by this questionnaire.

Methods

We recruited 314 persons to complete the questionnaire and to answer several demographic questions. We determined if the data was factorable by performing Bartlett’s test of sphericity and the Kaiser–Meyer–Olkin measure of sampling adequacy. We used the Factor package in Jamovi statistical software to perform EFA. We employed an Oblimin rotation and a Principal Axis extraction method. We also calculated the internal consistency of the questionnaire as a whole as well as each individual question.

Results

Our sample consisted of 265 (85%) women, 45 (14%) men, and 3 (1%) non-binary or other genders. The mean age of our participants was 34.65 (SD = 11.57, range = 18–65) years. EFA suggested a three-factor model. Questions 11, 13, 14, 15, and 16 measured one factor (we interpreted this as “Caregiving Roles”), questions 1, 3, 4, 8, 9, 10, 18, and 19 measured a different factor (“Traditionally Feminine Roles”), and questions 2, 5, 6, and 12 measured the “Traditionally Masculine Roles”. The questionnaire and each individual question demonstrated excellent internal consistency (Cronbach's α > 0.90).

Conclusion

The Home and Family Work Roles Questionnaire may measure three distinct factors, which we have named Caregiving, Traditionally Feminine, and Traditionally Masculine Roles. This aligns with the theory used in developing the questionnaire. Separation of the Home and Family Work Roles Questionnaire into three sub-scales with distinct scores is recommended to measure each of the recommended constructs.
Maximizing the cost-effectiveness of cervical screening in the context of routine HPV vaccination by optimizing screening strategies with respect to vaccine uptake: a modeling analysis
Authors: Choi Horace C. W. , Leung Kathy , Chan Karen K. L. , Bai Yuan , Jit Mark , Wu Joseph T.
Published: February 2023

Background

Regarding primary and secondary cervical cancer prevention, the World Health Organization proposed the cervical cancer elimination strategy that requires countries to achieve 90% uptake of human papillomavirus (HPV) vaccines and 70% screening uptake. The optimal cervical screening strategy is likely different for unvaccinated and vaccinated cohorts upon national HPV immunization. However, health authorities typically only provide a one-size-fits-all recommendation for the general population. We aimed to evaluate the cost-effectiveness for determining the optimal screening strategies for vaccinated and unvaccinated cohorts.

Methods

We considered the women population in Hong Kong which has a unique HPV infection and cervical cancer epidemiology compared to other regions in China and Asia. We used mathematical models which comprise a deterministic age-structured compartmental dynamic component and a stochastic individual-based cohort component to evaluate the cost-effectiveness of screening strategies for cervical screening. Following the recommendations in local guidelines in Hong Kong, we considered strategies that involved cytology, HPV testing, or co-testing as primary cervical screening. We also explored the impacts of adopting alternative de-intensified strategies for vaccinated cohorts. The 3-year cytology screening was used as the base comparator while no screening was also considered for vaccinated cohorts. Women’s lifetime life years, quality-adjusted life years, and costs of screening and treatment were estimated from the societal perspective based on the year 2022 and were discounted by 3% annually. Incremental cost-effectiveness ratios (ICERs) were compared to a willingness to pay (WTP) threshold of one gross domestic product per capita (US $47,792). Probabilistic and one-way sensitivity analyses were conducted.

Results

Among unvaccinated cohorts, the strategy that adds reflex HPV to triage mild cytology abnormality generated more life years saved than cytology-only screening and could be a cost-effective alternative. Among vaccinated cohorts, when vaccine uptake was 85% (based on the uptake in 2022), all guideline-based strategies (including the cytology-only screening) had ICERs above the WTP threshold when compared with no screening if the vaccine-induced protection duration was 20 years or longer. Under the same conditions, HPV testing with genotyping triage had ICERs (compared with no screening) below the WTP threshold if the routine screening interval was lengthened to 10 and 15 years or screening was initiated at ages 30 and 35 years.

Conclusions

HPV testing is a cost-effective alternative to cytology for vaccinated cohorts, and the associated optimal screening frequency depends on vaccine uptake. Health authorities should optimize screening recommendations by accounting for population vaccine uptake.
Higher white-nose syndrome fungal isolate yields from UV-guided wing biopsies compared with skin swabs and optimal culture media
Authors: Seidlova Veronika , Pikula Jiri , Kolarik Miroslav , Nováková Alena , Cmokova Adela , Ghazaryan Astghik , Nemcova Monika , Bednarikova Sarka , Patra Sneha , Kokurewicz Tomasz , Piacek Vladimir , Zukal Jan
Published: February 2023

Background

North American bat populations have suffered severe declines over the last decade due to the Pseudogymnoascus destructans fungus infection. The skin disease associated with this causative agent, known as white-nose syndrome (WNS), is specific to bats hibernating in temperate regions. As cultured fungal isolates are required for epidemiological and phylogeographical studies, the purpose of the present work was to compare the efficacy and reliability of different culture approaches based on either skin swabs or wing membrane tissue biopsies for obtaining viable fungal isolates of P. destructans.

Results

In total, we collected and analysed 69 fungal and 65 bacterial skin swabs and 51 wing membrane tissue biopsies from three bat species in the Czech Republic, Poland and the Republic of Armenia. From these, we obtained 12 viable P. destructans culture isolates.

Conclusions

Our results indicated that the efficacy of cultures based on wing membrane biopsies were significantly higher. Cultivable samples tended to be based on collections from bats with lower body surface temperature and higher counts of UV-visualised lesions. While cultures based on both skin swabs and wing membrane tissue biopsies can be utilised for monitoring and surveillance of P. destructans in bat populations, wing membrane biopsies guided by UV light for skin lesions proved higher efficacy. Interactions between bacteria on the host's skin also appear to play an important role.
Revealing novel pyroptosis-related therapeutic targets for sepsis based on machine learning
Authors: Chen Ying , Wang Xingkai , Wang Jiaxin , Zong Junwei , Wan Xianyao
Published: February 2023

Background

Sepsis is one of the most lethal diseases worldwide. Pyroptosis is a unique form of cell death, and the mechanism of interaction with sepsis is not yet clear. The aim of this study was to uncover pyroptosis genes associated with sepsis and to provide early therapeutic targets for the treatment of sepsis.

Methods

Based on the GSE134347 dataset, sepsis-related genes were mined by differential expression analysis and weighted gene coexpression network analysis (WGCNA). Subsequently, the sepsis-related genes were analysed for enrichment, and a protein‒protein interaction (PPI) network was constructed. We performed unsupervised consensus clustering of sepsis patients based on 33 pyroptosis-related genes (PRGs) provided by prior reviews. We finally obtained the PRGs mostly associated with sepsis by machine learning prediction models combined with prior reviews. The GSE32707 dataset served as an external validation dataset to validate the model and PRGs via receiver operating characteristic (ROC) curves. The NetworkAnalyst online tool was utilized to create a ceRNA network of lncRNAs and miRNAs around PRGs mostly associated with sepsis.

Results

A total of 170 genes associated with sepsis and 13 hub genes were acquired by WGCNA and PPI network analysis. The results of the enrichment analysis implied that these genes were mainly involved in the regulation of the inflammatory response and the positive regulation of bacterial and fungal defence responses. The prolactin signalling pathway and IL-17 signalling pathway were the primary enrichment pathways. Thirty-three PRGs can effectively classify septic patients into two subtypes, implying that there is a reciprocal relationship between sepsis and pyroptosis. Eventually, NLRC4 was considered the PRG most strongly associated with sepsis. The validation results of the prediction model and NLRC4 based on ROC curves were 0.74 and 0.67, respectively, both of which showed better predictive values. Meanwhile, the ceRNA network consisting of 6 lncRNAs and 2 miRNAs was constructed around NLRC4.

Conclusion

NLRC4, as the PRG mostly associated with sepsis, could be considered a potential target for treatment. The 6 lncRNAs and 2 miRNAs centred on NLRC4 could serve as a further research direction to uncover the deeper pathogenesis of sepsis.
Malaria patient spectrum representation in therapeutic clinical trials of uncomplicated malaria: a scoping review of the literature
Authors: Arena Lorenzo , Zanamwe Mazvita , Halleux Christine M. , Carrara Verena , Angus Brian J. , Ariana Proochista , Humphreys Georgina S. , Richmond Caitlin , Stepniewska Kasia , Guérin Philippe J. , Olliaro Piero L.
Published: February 2023

Background

For the results of clinical trials to have external validity, the patients included in the study must be representative of the population presenting in the general clinical settings. A scoping literature review was performed to evaluate how the eligibility criteria used in anti-malarial efficacy and safety trials translate into patient selection.

Methods

A search of the WorldWide Antimalarial Resistance Network (WWARN) Clinical Trials Publication Library, MEDLINE, The Cochrane Library, and clinicaltrials.gov was conducted to identify trials investigating anti-malarial efficacy and safety, published between 14th April 2001 and 31st December 2017. An updated search using the WWARN Clinical Trial Publication Library was undertaken to identify eligible publications from 1st January 2018 to 31st July 2021. The review included studies in patients of any age with uncomplicated malaria and any pharmaceutical therapeutic intervention administered. The proportion of trials with malaria-positive patients excluded was calculated and linked to the reported reason for exclusion. A subgroup analysis on eligibility criteria and trial baseline demographics was conducted to assess whether criteria are complied with when recruiting patients.

Results

Out of 847 studies, 176 (21%) trials were included in the final synthesis, screening a total of 157,516 malaria-positive patients, of whom 56,293 (36%) were enrolled and treated. Across the 176 studies included, 84 different inclusion and exclusion criteria were identified. The reason for exclusion of patients who tested positive for malaria was reported in 144 (82%) studies. Three criteria account for about 70% of malaria-positive patients excluded: mixed-species malaria infections or other specific Plasmodium species, parasite counts outside the set study ranges, and refusal of consent.

Conclusions

Nearly two-thirds of the malaria-positive subjects who present to health facilities are systematically excluded from anti-malarial treatment trials. Reasons for exclusions are largely under-reported. Anti-malarial treatment in the general population is informed by studies on a narrow selection of patients who do not fully represent the totality of those seeking antimalarial treatment in routine practice. While entry criteria ensure consistency across trials, pragmatic trials are also necessary to supplement the information currently available and improve the external validity of the findings of malaria clinical trials.
Notification of malaria cases in the Brazilian Amazon Basin from 2010 to 2020: an analysis of the reporting times
Authors: Ayala Mario J. C. , Valiati Naiara C. M. , Bastos Leonardo S. , Villela Daniel A. M.
Published: February 2023

Background

As controlling malaria transmission remains a public-health challenge in the Brazilian Amazon basin, the National Surveillance System for Malaria (SIVEP-MALARIA) has registered malaria notifications for over fifteen years helping in the decision-making on control and elimination. As a surveillance database, the system is prone to reporting delays, and knowledge about reporting patterns is essential in decisions.

Methods

This study contains an analysis of temporal and state trends of reporting times in a total of 1,580,617 individual malaria reports from January 2010 to December 2020, applying procedures for statistical distribution fitting. A nowcasting technique was applied to show an estimation of number of cases using a statistical model of reporting delays.

Results

Reporting delays increased over time for the states of Amazonas, Rondônia, Roraima, and Pará. Amapá has maintained a similar reporting delay pattern, while Acre decreased reporting delay between 2010 and 2020. Predictions were more accurate in states with lower reporting delays. The temporal evolution of reporting delays only showed a decrease in malaria reports in Acre from 2010 to 2020.

Conclusion

Malaria notifications may take days or weeks to enter the national surveillance database. The reporting times are likely to impact incidence estimation over periods when data is incomplete, whilst the impact of delays becomes smaller for retrospective analysis. Short-term assessments for the estimation of malaria incidence from the malaria control programme must deal with reporting delays.
Effect of omega-3 supplementation on lipid profile in children and adolescents: a systematic review and meta-analysis of randomized clinical trials
Authors: Khorshidi Masoud , Hazaveh Zohreh Sajadi , Alimohammadi-kamalabadi Malek , Jamshidi Sanaz , Moghaddam Omid Moradi , Olang Beheshteh , Hatefi Sayeh , Hosseini Amirhossein , Jamilian Parsa , Zarezadeh Meysam , Kohansal Parichehr , Heshmati Javad , Jamilian Parmida , Sayyari Aliakbar
Published: February 2023

Purpose

Dyslipidemia is considered as a known risk factor for cardiovascular disease. Yet various trials with wide ranges of doses and durations have reported contradictory results. We undertook this meta-analysis of randomized controlled trials (RCTs) to determine whether omega-3 supplementation can affect lipid profile in children and adolescents.

Methods

Cochrane Library, Embase, PubMed, and Scopus databases were searched up to March 2021. Meta-analysis was performed using random-effect method. Effect size was expressed as weighted mean difference (WMD) and 95% confidence interval (CI). Heterogeneity was assessed using the I2index. In order to identification of potential sources of heterogeneity, predefined subgroup and meta-regression analysis was conducted.

Results

A total of 14 RCTs with 15 data sets were included. Based on the combination of effect sizes, there was a significant reduction in TG levels (WMD: -15.71 mg/dl, 95% CI: -25.76 to -5.65,P=0.002), with remarkable heterogeneity (I2=88.3%,P<0.001). However, subgroup analysis revealed that omega-3 supplementation significantly decreased TG only in studies conducted on participants ≤13 years old (WMD=-25.09, 95% CI: -43.29 to -6.90,P=0.007), (I2=84.6%,P<0.001) and those with hypertriglyceridemia (WMD=-28.26, 95% CI: -39.12 to -17.41,P<0.001), (I2=0.0%,P=0.934). Omega-3 supplementation had no significant effect on total cholesterol, HDL, and LDL levels. Also, results of nonlinear analysis showed significant effect of treatment duration on HDL status (Pnon-linearity=0.047).

Conclusion

Omega-3 supplementation may significantly reduce TG levels in younger children and those with hypertriglyceridemia. Also, based on the HDL-related results, clinical trials with longer duration of intervention are recommended in this population.
Cyclists’ exposure to air pollution, noise, and greenery: a population-level spatial analysis approach
Authors: Willberg Elias , Poom Age , Helle Joose , Toivonen Tuuli
Published: February 2023

Urban travel exposes people to a range of environmental qualities with significant health and wellbeing impacts. Nevertheless, the understanding of travel-related environmental exposure has remained limited. Here, we present a novel approach for population-level assessment of multiple environmental exposure for active travel. It enables analyses of (1) urban scale exposure variation, (2) alternative routes’ potential to improve exposure levels per exposure type, and (3) by combining multiple exposures. We demonstrate the approach’s feasibility by analysing cyclists’ air pollution, noise, and greenery exposure in Helsinki, Finland. We apply an in-house developed route-planning and exposure assessment software and integrate to the analysis 3.1 million cycling trips from the local bike-sharing system. We show that especially noise exposure from cycling exceeds healthy thresholds, but that cyclists can influence their exposure by route choice. The proposed approach enables planners and individual citizens to identify (un)healthy travel environments from the exposure perspective, and to compare areas in respect to how well their environmental quality supports active travel. Transferable open tools and data further support the implementation of the approach in other cities.
Cell–cell communications shape tumor microenvironment and predict clinical outcomes in clear cell renal carcinoma
Authors: Chen Liu-xun , Zeng Shen-jie , Liu Xv-dong , Tang Hai-bin , Wang Jia-wu , Jiang Qing
Published: February 2023

Background

Cell–cell communications of various cell populations within tumor microenvironment play an essential role in primary tumor growth, metastasis evolution, and immune escape. Nevertheless, comprehensive investigation of cell–cell communications in the ccRCC (Clear cell renal carcinoma) microenvironment and how this interplay affects prognosis still remains limited.

Methods

Intercellular communications were characterized by single-cell data. Firstly, we employed “CellChat” package to characterize intercellular communications across all types of cells in microenvironment in VHL mutated and non-mutated samples from 8 patients, respectively. And pseudotime trajectory analyses were performed with monocle analyses. Finally clinical prognosis and immunotherapy efficacy with different landscapes of intercellular interplay are evaluated by TCGA-KIRC and immunotherapy cohort.

Results

Firstly, the VHL phenotype may be related to the intercellular communication landscape. And trajectory analysis reveals the potential relationship of cell–cell communication molecules with T cells and Myeloid cells differentiation. Furthermore, those molecules also correlate with the infiltration of T cells and Myeloid cells. A tumor cluster with highly expressed ligands was defined by quantitative analysis and transcription factor enrichment analysis, which was identified to be pivotal for intercellular communications in tumor microenvironment. Finally, bulk data indicates bulk that different clusters with different intercellular communications have significant predictive value for prognosis and distinguished immunotherapy efficiency.

Conclusions

The intercellular communication landscapes of VHL wild and VHL mutant ccRCC vary. Intercellular communications within the tumor microenvironment also influence T cell and myeloid cell development and infiltration, as well as predict clinical prognosis and immunotherapy efficacy in ccRCC.
Bone density of the axis (C2) measured using Hounsfield units of computed tomography
Authors: Simion George , Eckardt Niklas , Senft Christian , Schwarz Falko
Published: February 2023

Introduction

The assessment of bone density is of great importance nowadays due to the increasing age of patients. Especially in regard to the surgical stabilization of the spine, the assessment of bone density is important for therapeutic decision making. The aim of this work was to record trabecular bone density values using Hounsfield units of the second cervical vertebra.

Material and methods

The study is a monocentric retrospective data analysis of 198 patients who received contrast-enhanced polytrauma computed tomography in a period of two years at a maximum care hospital. Hounsfield units were measured in three different regions within the C2: dens, transition area between dens and vertebral body and vertebral body. The measured Hounsfield units were converted into bone density values using a validated formula.

Results

A total of 198 patients were included. The median bone density varied in different regions of all measured C2 vertebrae: in the dens axis, C2 transition area between dens and vertebral body, and in the vertebral body bone densities were 302.79 mg/cm3, 160.08 mg/cm3, and 240.31 mg/cm3, respectively. The transition area from dens axis to corpus had statistically significant lower bone density values compared to the other regions (p < 0.001). There was a decrease in bone density values after age 50 years in both men and women (p < 0.001).

Conclusions

The transitional area from dens axis to corpus showed statistically significant lower bone density values compared to the adjacent regions (p < 0.001). This area seems to be a predilection site for fractures of the 2nd cervical vertebra, which is why special attention should be paid here in radiological diagnostics after a trauma.
Prevalence and clustering of cardiovascular risk factors among resident of coastal areas in Qinzhou, Guangxi, China
Authors: He Fang , Liao Zhennan , Li Yu-Mei , Luo Yuanling , Wu Lili , Lin Liping , Chen Ying , Deng Weihong , Huang Junzhang
Published: February 2023

Objective

We aimed to estimate the prevalence of CRFs and investigate its associated social-economic factors among adults in coastal areas of Qinzhou, Guangxi.

Methods

A representative sample of 1836 participants aged 20 to 70 years was included in Qinzhou, Guangxi in 2020. Data were collected by the questionnaire, anthropometric and laboratory measurements. The prevalence of CRFs, including hypertension, dyslipidemia, diabetes, overweight or obesity, alcohol consumption, and smoking were calculated by standardization. The multivariate logistic regression analysis was performed to explore the independent factors associated with the presence of CRFs.

Results

The age-standardized prevalence of hypertension, dyslipidemia, diabetes, overweight or obesity alcohol consumption, and smoking was 42.7%, 39.5%, 0.9%, 38.5%, 18.4% and 15.7%, respectively. The prevalence of clustering of at least one and at least two cardiovascular disease risk factors were 82.2% and 45.3% in total. There were differences in the aggregation of cardiovascular risk factors among different age, education, and income levels. There appeared higher clustering of at least one and at least two CRFs among adults with lower education level, higher income level and those elderly.

Conclusions

Compared with other regions in China, a higher prevalence of CRFs exists among adults in Guangxi and several social-economic factors were associated with the presence of CRFs. These findings suggest that we should implement effective measures to control the CRFs, to reduce the risk of cardiovascular disease in adults.
METTL3 depletion contributes to tumour progression and drug resistance via N6 methyladenosine-dependent mechanism in HR+HER2—breast cancer
Authors: Ouyang Dengjie , Hong Tao , Fu Mengdie , Li Yitong , Zeng Liyun , Chen Qitong , He Hongye , Wen Ying , Cheng Yan , Zhou Meirong , Zou Qiongyan , Yi Wenjun
Published: February 2023

Background

Chemotherapy is an important strategy for the treatment of hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+HER2−) breast cancer (BC), but this subtype has a low response rate to chemotherapy. Growing evidence indicates that N6-methyladenosine (m6A) is the most common RNA modification in eukaryotic cells and that methyltransferase-like 3 (METTL3) participates in tumour progression in several cancer types. Therefore, exploring the function of METTL3 in HR+HER2− BC initiation and development is still important.

Methods

mRNA and protein expression levels were analysed by quantitative real-time polymerase chain reaction and western blotting, respectively. Cell proliferation was detected by CCK-8 and colony formation assays. Cell cycle progression was assessed by flow cytometry. Cell migration and invasion were analysed by wound healing assays and transwell assays, respectively, and apoptosis was analysed by TUNEL assays. Finally, m6A modification was analysed by methylated RNA immunoprecipitation.

Results

Chemotherapy-induced downregulation of the m6A modification is regulated by METTL3 depletion in HR+HER2− BC. METTL3 knockdown in MCF-7/T47D cells decreased the drug sensitivity of HR+HER2− BC cells by promoting tumour proliferation and migration and inhibiting apoptosis. Mechanistically, CDKN1A is a downstream target of METTL3 that activates the AKT pathway and promotes epithelial-mesenchymal transformation (EMT). Moreover, a decrease in BAX expression was observed when m6A modification was inhibited with METTL3 knockdown, and apoptosis was inhibited by the reduction of caspase-3/-9/-8.

Conclusion

METTL3 depletion promotes the proliferation and migration and decreases the drug sensitivity of HR+HER2− BC via regulation of the CDKN1A/EMT and m6A-BAX/caspase-9/-3/-8 signalling pathways, which suggests METTL3 played a tumour-suppressor role and it could be a potential biomarker for predicting the prognosis of patients with HR+HER2− BC.
Risks of second non-breast primaries following breast cancer in women: a systematic review and meta-analysis
Authors: Allen Isaac , Hassan Hend , Sofianopoulou Eleni , Eccles Diana , Turnbull Clare , Tischkowitz Marc , Pharoah Paul , Antoniou Antonis C.
Published: February 2023

Background

Second primary cancer incidence is rising among breast cancer survivors. We examined the risks of non-breast second primaries, in combination and at specific cancer sites, through a systematic review and meta-analysis.

Methods

We conducted a systematic search of PubMed, Embase, and Web of Science, seeking studies published by March 2022. We included studies that reported standardized incidence ratios (SIRs), with associated standard errors, assessing the combined risk of second non-breast primaries following breast cancer. We performed meta-analyses of combined second primary risks, stratifying by age, follow-up duration, and geographic region. We also assessed second primary risks at several specific sites, stratifying by age. The inverse variance method with DerSimonian–Laird estimators was used in all meta-analyses, assuming a random-effects model. Associated biases and study quality were evaluated using the Newcastle–Ottawa scale.

Results

One prospective and twenty-seven retrospective cohort studies were identified. SIRs for second non-breast primaries combined ranged from 0.84 to 1.84. The summary SIR estimate was 1.24 (95% CI 1.14–1.36,I2: 99%). This varied by age: the estimate was 1.59 (95% CI 1.36–1.85) when breast cancer was diagnosed before age 50, which was significantly higher than in women first diagnosed at 50 or over (SIR: 1.13, 95% CI 1.01–1.36,pfor difference: < 0.001). SPC risks were also significantly higher when based on Asian, rather than European, registries (Asia—SIR: 1.47, 95% CI 1.29–1.67. Europe—SIR: 1.16, 95% CI 1.04–1.28). There were significantly increased risks of second thyroid (SIR: 1.89, 95% CI 1.49–2.38), corpus uteri (SIR: 1.84, 95% CI 1.53–2.23), ovary (SIR: 1.53, 95% CI 1.35–1.73), kidney (SIR: 1.43, 95% CI 1.17–1.73), oesophagus (SIR: 1.39, 95% CI 1.26–1.55), skin (melanoma) (SIR: 1.34, 95% CI 1.18–1.52), blood (leukaemia) (SIR: 1.30, 95% CI 1.17–1.45), lung (SIR: 1.25, 95% CI 1.03–1.51), stomach (SIR: 1.23, 95% CI 1.12–1.36) and bladder (SIR: 1.15, 95% CI 1.05–1.26) primaries.

Conclusions

Breast cancer survivors are at significantly increased risk of second primaries at many sites. Risks are higher for those diagnosed with breast cancer before age 50 and in Asian breast cancer survivors compared to European breast cancer survivors. This study is limited by a lack of data on potentially confounding variables. The conclusions may inform clinical management decisions following breast cancer, although specific clinical recommendations lie outside the scope of this review.
Intraoperative hypovolemia as a possible precipitating factor for pituitary apoplexy: a case report
Authors: Abo Kristine M. , Kane Joseph , Druckenbrod Rachel C. , Mooney Michael A. , Rachlin Jacob
Published: February 2023

Background

Pituitary apoplexy is acute infarction with or without hemorrhage of the pituitary gland. It is a rare but potentially life-threatening emergency that most commonly occurs in the setting of pituitary adenoma. The mechanisms underlying pituitary apoplexy are not well understood, but are proposed to include factors of both hemodynamic supply and adenoma demand. In the case of patients with known pituitary macroadenomas undergoing major surgery for other indications, there is a theoretically increased risk of apoplexy in the setting of “surgical stress.” However, risk stratification of patients with nonfunctioning pituitary adenomas prior to major surgery is challenging because the precipitating factors for pituitary apoplexy are not completely understood. Here we present a case in which intraoperative hypovolemia is a possible mechanistic precipitating factor for pituitary apoplexy.

Case presentation

A 76-year-old patient with a known hypofunctioning pituitary macroadenoma underwent nephrectomy for renal cell carcinoma, during which there was significant intraoperative blood loss. He became symptomatic with ophthalmoplegia on the second postoperative day, and was diagnosed with pituitary apoplexy. He was managed conservatively with cortisol replacement therapy, and underwent therapeutic anticoagulation 2 months after pituitary apoplexy for deep vein thrombosis. His ophthalmoplegia slowly resolved over months of follow-up. Pituitary apoplexy did not recur with therapeutic anticoagulation.

Conclusions

When considering the risk of surgery in patients with a known pituitary macroadenoma, an operation with possible high-volume intraoperative blood loss may have increased risk of pituitary apoplexy because intraoperative hypovolemia may precipitate ischemia, infarction, and subsequent hemorrhage. This may be particularly relevant in the cases of elective surgery. Additionally, we found that we were able to therapeutically anticoagulate a patient 2 months after pituitary apoplexy for the management of deep vein thrombosis without recurrence of pituitary apoplexy.
The hen and the egg question in atopic dermatitis: allergy or eczema comes first
Authors: Allenova Anastasiia , Darlenski Razvigor
Published: February 2023

Atopic dermatitis (AD) as a chronic inflammatory systemic condition is far more than skin deep. Co-morbidities such as asthma and allergic rhinitis as well as the psychological impact influence seriously the quality of life of the patients. Recent studies have shown that only 10% of atopic patients undergo full manifestation of the atopic march, while 40% demonstrate concomitant food allergy. Exposure to food allergens in the environment causes sensitization and food allergy through the disruption of the skin barrier, as in AD. Food allergy and AD are closely related. While not all AD patients have a food allergy, 20–40% of children with moderate to severe AD will have an IgE-mediated food allergy. It is known that they may coexist but it is unclear if food allergy worsens the course of AD. Experimental, clinical, and epidemiological studies have provided evidence of the primary role of an epidermal barrier defect in the development of sensitization to environmental allergens and that this process occurs in the damaged skin barrier rather than the gastrointestinal or respiratory tract. There is strong evidence for a connection between early AD onset and the development of other allergic diseases later in life.
Results of interventional treatment of peripheral slow-flow malformations
Authors: Altenbernd Jens , Kutta Felix , Forsting Michael , Theysohn Jens , Rohde Stefan
Published: February 2023

Background

In recent years sclerotherapy has increasingly become the treatment of choice for peripheral slow-flow malformations. However, the long-term effectiveness of sclerotherapy is still a matter of debate, especially when it comes to new sclerosing agents like polidocanol. This study aims at gathering further information concerning its long-term effectiveness and safety.

Results

Most patients reported a reduction of symptoms which include pain (57,7%), swelling (65,4%) and functional impairment (60%). Cosmetic complaints were less likely to be reduced by sclerotherapy (44,4%). In most cases a relief of symptoms was stable for many years, especially after several consecutive treatment sessions. Complication rates were comparably low, with only 2 patients requiring additional treatment at hospital and no lasting damages. (…) (7) Most patients (70,9%) were at least partially satisfied with the treatment. Satisfaction was closely linked to a partial or complete relief of symptoms (p = 0.001).

Conclusion

Sclerotherapy is a promising way of treating slow-flow-malformations. Polidocanol has proved to be a save sclerosing agent. The reduction of major symptoms was substantial in most cases and lasted for many years.