bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic options for pulmonary fungal diseases in Africa
Authors: Mushi Martha F. , Zaki Sherif M. , Penney Richard O.S. , Bamba Sanata , Ngouanom Kuate Marius Paulin , Kasamba Eric L. , Amona Fructueux M. , Werkneh Sara , Ceesay Buntung , Dibba Bakary , Ocansey Bright , Sy Ousmane , Yahaya Mohammed , Jiba Darlinda , Boyles Tom , Mkumbaye Sixbert I. , Kwizera Richard , Sibanda Elopy , Koffi David , Sissinto Savi De Tove Yolande , Orefuwa Emma , Denning David W.
Published: March 2023

Background

Fungal lung diseases are global in distribution and require specific tests for diagnosis. We report a survey of diagnostic service provision in Africa.

Methods

A written questionnaire was followed by a video conference call with each respondent(s) and external validation. To disseminate the questionnaire, a snowball sample was used.

Results

Data were successfully collected from 50 of 51 African countries with populations >1 million. The questionnaire was completed by respondents affiliated with 72 health facilities. Of these 72 respondents, 33 (45.8%) reported data for the whole country while others reported data for a specific region/province within their country. In the public sector, chest X-ray and computed tomography are performed often in 49 countries (98%) and occasionally in 37 countries (74%), and less often in the private sector. Bronchoscopy and spirometry were done often in 28 countries (56%) and occasionally in 18 countries (36%) in the tertiary health facilities of public sector. The most conducted laboratory diagnostic assay was fungal culture (often or occasionally) in 29 countries (58%). In collaboration with the Africa Centre for Disease Control and Prevention, regional webinars and individual country profiles provided further data validation.

Conclusion

This survey has found a huge disparity of diagnostic test capability across the African continent. Some good examples of good diagnostic provision and very high-quality care were seen, but this was unusual. The unavailability of essential testing such as spirometry was noted, which has a high impact in the diagnosis of lung diseases. It is important for countries to implement tests based on the World Health Organization Essential Diagnostics List.
Smartphone-based cough monitoring as a near real-time digital pneumonia biomarker
Authors: Boesch Maximilian , Rassouli Frank , Baty Florent , Schwärzler Anja , Widmer Sandra , Tinschert Peter , Shih Iris , Cleres David , Barata Filipe , Fleisch Elgar , Brutsche Martin H.
Published: March 2023

Background

Cough represents a cardinal symptom of acute respiratory tract infections. Generally associated with disease activity, cough holds biomarker potential and might be harnessed for prognosis and personalised treatment decisions. Here, we tested the suitability of cough as a digital biomarker for disease activity in coronavirus disease 2019 (COVID-19) and other lower respiratory tract infections.

Methods

We conducted a single-centre, exploratory, observational cohort study on automated cough detection in patients hospitalised for COVID-19 (n=32) and non-COVID-19 pneumonia (n=14) between April and November 2020 at the Cantonal Hospital St Gallen, Switzerland. Cough detection was achieved using smartphone-based audio recordings coupled to an ensemble of convolutional neural networks. Cough levels were correlated to established markers of inflammation and oxygenation.

Measurements and main results

Cough frequency was highest upon hospital admission and declined steadily with recovery. There was a characteristic pattern of daily cough fluctuations, with little activity during the night and two coughing peaks during the day. Hourly cough counts were strongly correlated with clinical markers of disease activity and laboratory markers of inflammation, suggesting cough as a surrogate of disease in acute respiratory tract infections. No apparent differences in cough evolution were observed between COVID-19 and non-COVID-19 pneumonia.

Conclusions

Automated, quantitative, smartphone-based detection of cough is feasible in hospitalised patients and correlates with disease activity in lower respiratory tract infections. Our approach allows for near real-time telemonitoring of individuals in aerosol isolation. Larger trials are warranted to decipher the use of cough as a digital biomarker for prognosis and tailored treatment in lower respiratory tract infections.
Short-acting β2-agonists and exacerbations in children with asthma in England: SABINA Junior
Authors: Morgan Ann , Maslova Ekaterina , Kallis Constantinos , Sinha Ian , Roberts Graham , Tran Trung N. , van der Valk Ralf J.P. , Quint Jennifer K.
Published: March 2023

Background

Prescription of three or more short-acting β2-agonist (SABA) canisters per year in adult and adolescent asthma populations is associated with a risk of severe exacerbations; however, evidence in children aged <12 years is limited.

Methods

This study analysed data on children and adolescents with asthma in three age cohorts: 1‒5 years, 6‒11 years and 12‒17 years from the Clinical Practice Research Datalink Aurum database for the period 1 January 2007 to 31 December 2019. Associations between SABA prescriptions (three or moreversusfewer than three canisters per year) at baseline, defined as 6 months after an asthma diagnosis as a binary exposure variable, and the rate of future asthma exacerbations, defined as oral corticosteroid burst therapy, an emergency department visit or hospital admission, were assessed by multilevel negative binomial regression, adjusted for relevant demographic and clinical confounders.

Results

Overall 48 560, 110 091 and 111 891 paediatric patients with asthma were aged 1‒5, 6‒11 and 12‒17 years, respectively. During the baseline period, 22 423 (46.2%), 42 137 (38.3%) and 40 288 (36.0%) in these three age cohorts, respectively, were prescribed three or more SABA canisters per year. Across all age ranges, the rate of future asthma exacerbations in those prescribed three or moreversusfewer than three SABA canisters per year was at least two-fold higher. >30% of patients across all age cohorts were not prescribed inhaled corticosteroids (ICS), and the median proportion of days covered was only 33%, suggesting inadequate prescribing of ICS

Conclusion

In children, higher SABA prescriptions at baseline were associated with increased future exacerbation rates. These findings highlight the need for monitoring prescription of three or more SABA canisters per year to identify children with asthma at risk of exacerbations.
ERS International Congress 2022: highlights from the Thoracic Surgery and Lung Transplantation Assembly
Authors: Magouliotis Dimitrios E. , Bos Saskia , Esendagli Dorina , Nardini Marco , Migliore Marcello , Perch Michael , Cardillo Giuseppe , Meloni Federica , Ricciardi Sara , Hellemons Merel
Published: March 2023

The thoracic surgery and lung transplantation assembly (Assembly 8) of the European Respiratory Society (ERS) is delighted to present the highlights from the 2022 ERS International Congress that took place in a hybrid version in Barcelona, Spain. We have selected the four main sessions that discussed recent advances across a wide range of topics including the effects of coronavirus disease 2019 on thoracic surgery and the challenges regarding lung transplantation in connective tissue diseases and common variable immunodeficiency. The sessions are summarised by early career members in close collaboration with the assembly faculty. We aim to provide the reader with an update and enhanced insight into the highlights of the conference in the fields of thoracic surgery and lung transplantation.
Efficacy and tolerability of zinc acetate for treatment of chronic refractory cough: pilot randomised futility trial
Authors: Balasubramanian Aparna , Holbrook Janet T. , Canning Brendan J. , Que Loretta G. , Castro Mario , Make Barry J. , Rogers Linda , Busk Michael F. , Rea Alexis , McCook-Veal Ashley A. , He Jiaxian , McCormack Meredith C. , Wise Robert A.
Published: March 2023

Background:

Cough is the most reported symptom in the United States, with chronic refractory cough representing significant morbidity to patients. Zinc acetate may have beneficial effects in the cough reflex pathway. We sought to assess the safety and efficacy of zinc acetate in the management of chronic refractory cough.

Study design and methods:

This was a randomised, placebo-controlled, parallel-design pilot trial of individuals with chronic refractory cough. The effects of 6 weeks of zinc acetateversusplacebo on quality of life and symptoms as measured by the Cough Quality-of-Life Questionnaire (CQLQ), Leicester Cough Questionnaire (LCQ), cough visual analogue score (C-VAS) and Global Assessment of Change in Cough (GACC) scores were evaluated. A futility analysis plan with a one-sided 80% confidence interval was used to compare treatment effect to published minimum clinically important differences (MCID) for each outcome.

Results:

34 participants, 17 in each group, were enrolled and randomised. Participants were primarily white females with moderate–severe cough. Participants assigned to zinc acetate had a significant increase in serum zinc levels after 6 weeks, while those assigned to placebo did not. Both groups showed improvement in CQLQ, LCQ, C-VAS and GACC scores, but the treatment effects of zinc acetateversusplacebo were small with confidence intervals that did not include the MCIDs.

Interpretation:

We observed no benefit of zinc therapy over placebo on cough symptoms or quality of life and conclude that larger trials of zinc for chronic cough are not warranted.
Evaluation of real-world mepolizumab use in severe asthma across Europe: the SHARP experience with privacy-preserving federated analysis
Authors: Kroes Johannes A. , Alfonso-Cristancho Rafael , Bansal Aruna T. , Berret Emmanuelle , Bieksiene Kristina , Bourdin Arnaud , Brussino Luisa , Canhoto Diogo , Cardini Cristina , Celik Gulfem , Csoma Zsuzsanna , Dahlén Barbro , Damadoglu Ebru , Eger Katrien , Gauquelin Lisa , Gemicioglu Bilun , Goksel Ozlem , Graff Sophie , Heffler Enrico , Hofstee Hendrik B. , Howarth Peter , Jakes Rupert W. , Jaun Fabienne , Kalinauskaite-Zukauske Virginija , Kopač Peter , Kwon Namhee , Loureiro Claudia C. , Lozoya García Victor , Masoli Matthew , Rezelj Mariana Paula , Pérez De Llano Luis , Popović-Grle Sanja , Ramos-Barbón David , Sà Sousa Ana , Samitas Konstantinos , Schleich Florence , Sirena Concetta , Skrgat Sabina , Zervas Eleftherios , Zichnalis George , Bel Elisabeth H. , Sont Jacob K. , Hashimoto Simone , Ten Brinke Anneke
Published: March 2023

Background

An objective of the Severe Heterogeneous Asthma Registry, Patient-centered (SHARP) is to produce real-world evidence on a pan-European scale by linking nonstandardised, patient-level registry data. Mepolizumab has shown clinical efficacy in randomised controlled trials and prospective real-world studies and could therefore serve as a proof of principle for this novel approach. The aim of the present study was to harmonise data from 10 national severe asthma registries and characterise patients receiving mepolizumab, assess its effectiveness on annual exacerbations and maintenance oral glucocorticoid (OCS) use, and evaluate treatment patterns.

Methods

In this observational cohort study, registry data (5871 patients) were extracted for harmonisation. Where harmonisation was possible, patients who initiated mepolizumab between 1 January 2016 and 31 December 2021 were examined. Changes of a 12-month (range 11–18 months) period in frequent (two or more) exacerbations, maintenance OCS use and dose were analysed in a privacy-preserving manner using meta-analysis of generalised estimating equation parameters. Periods before and during the coronavirus disease 2019 pandemic were analysed separately.

Results

In 912 patients who fulfilled selection criteria, mepolizumab significantly reduced frequent exacerbations (OR 0.18, 95% CI 0.13–0.25), maintenance OCS use (OR 0.75, 95% CI 0.61–0.92) and dose (mean −3.93 mg·day
−1
, 95% CI −5.24–2.62 mg·day
−1
) in the pre-pandemic group, with similar trends in the pandemic group. Marked heterogeneity was observed between registries in patient characteristics and mepolizumab treatment patterns.

Conclusions

By harmonising patient-level registry data and applying federated analysis, SHARP demonstrated the real-world effectiveness of mepolizumab on asthma exacerbations and maintenance OCS use in severe asthma patients across Europe, consistent with previous evidence. This paves the way for future pan-European real-world severe asthma studies using patient-level data in a privacy-proof manner.
Device-measured movement behaviors and cardiac biomarkers in older adults without major cardiovascular disease: the Seniors-ENRICA-2 study
Authors: Fabre-Estremera Blanca , Buño-Soto Antonio , García-Esquinas Esther , Cabanas-Sánchez Verónica , Martínez-Gómez David , Rodríguez-Artalejo Fernando , Ortolá Rosario
Published: March 2023

Background

High-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are biomarkers of myocardial infarction and heart failure, respectively, and indicate cardiovascular risk. Since low physical activity (PA) and sedentary behavior (SB) are also associated with higher cardiovascular risk, and this association could be a consequence of higher levels of cardiac biomarkers, we examined the association of device-measured movement behaviors with hs-cTnT and NT-proBNP in older men and women without major cardiovascular disease (CVD).

Methods

We used data from 1939 older adults from the Seniors-ENRICA-2 study. Accelerometers were used to assess time spent in sleep, SB, light PA (LPA), and moderate-to-vigorous PA (MVPA). Linear regression models were fitted separately in eight strata defined by sex, by median total PA time, and by the presence of subclinical cardiac damage according to cardiac biomarkers levels.

Results

In the less active men with subclinical cardiac damage, spending 30 min/day more of MVPA was associated with a mean percentage difference (MPD) (95% confidence interval) in hs-cTnT of − 13.1 (− 18.3, − 7.5); MPDs in NT-proBNP per 30 min/day increment were 5.8 (2.7, 8.9) for SB, − 19.3 (− 25.4, − 12.7) for LPA and − 23.1 (− 30.7, − 14.6) for MVPA. In women with subclinical cardiac damage who were less physically active, 30 min/day more of SB, LPA and MVPA were associated with MPDs in hs-cTnT of 2.1 (0.7, 3.6), − 5.1 (− 8.3, − 1.7) and − 17.5 (− 22.9, − 11.7), respectively, whereas in those more active, LPA and MVPA were associated with MPDs of 4.1 (1.2, 7.2) and − 5.4 (− 8.7, − 2.0), respectively. No associations were found with NT-proBNP in women.

Conclusions

The relationship between movement behaviors and cardiac biomarkers in older adults without major CVD depends on sex, subclinical cardiac damage and PA level. More PA and less SB were generally related to lower cardiac biomarkers levels among less active individuals with subclinical cardiac damage, with greater benefits for hs-cTnT in women than men and no benefits for NT-proBNP in women.
Trajectory of physical activity frequency and cancer risk: Findings from a population-based cohort study
Authors: Tran Thi Phuong Thao , Luu Ngoc Minh , Bui Thi Tra , Han Minji , Lim Min Kyung , Oh Jin-Kyoung
Published: March 2023

Background

Physical activity (PA) changes throughout an individual’s life, but the association between such changes and cancer risk seems to be overlooked in the literature. Thus, this study aimed to examine the association between the trajectories of PA frequency and cancer incidence among middle-aged Korean adults.

Methods

A total of 1,476,335 eligible participants (992,151 men and 484,184 women) aged ≥40 years from the National Health Insurance Service cohort (2002–2018) were included. Assessment of PA frequency was a self-reported measure, based on the question: “How many times per week do you perform exercise that makes you sweat?”. PA frequency trajectories (i.e., trajectory classes of change in PA frequency) from 2002 to 2008 were identified using group-based trajectory modeling. Cox proportional hazards regression was used to assess the associations between the PA trajectories and cancer incidence.

Results

Five PA frequency trajectories over 7 years were identified: persistently low (men:73.5%; women:74.7%), persistently moderate (men:16.2%; women:14.6%), high-to-low (men:3.9%; women:3.7%), low-to-high (men:3.5%; women:3.8%), and persistently high (men:2.9%; women:3.3%). Compared with persistently low frequency, maintaining a high PA frequency was associated with a lower risk of all cancers (Hazard ratio (HR) = 0.92, 95%CI = 0.87–0.98) and breast cancer (HR = 0.82, 95%CI = 0.70–0.96) among women. There was a lower risk for thyroid cancer among men in the high-to-low (HR = 0.83, 95%CI = 0.71–0.98), low-to-high (HR = 0.80, 95%CI = 0.67–0.96), and high PA trajectories (HR = 0.82, 95%CI = 0.68–0.99). There was a significant association between moderate trajectory and lung cancer in men (HR = 0.88, 95%CI = 0.80–0.95), in both smoking and non-smoking men.

Conclusion

Long-term persistent high frequency of PA as part of the daily routine should be widely promoted and encouraged to reduce the risk for all cancer development in women.
Evaluating the quality of the public transport service during the COVID-19 pandemic from the perception of two user groups
Authors: Ismael Karzan , Esztergár-Kiss Domokos , Duleba Szabolcs
Published: March 2023

The current paper focuses on a comparative analysis of both public transport (PT) and private vehicle (PV) users’ perceptions on the quality of the service. To detect the key components of PT attributes a new hybrid methodology is applied, combining the importance-performance analysis and the importance-performance map analysis. The proposed hybrid approach is simpler and more integrated than the existing methods in the literature. The sample comprises an online panel and a total of 1028 questionnaires for PV and PT users surveyed during the pandemic period in Budapest. The results of the applied methods show that among the different groups, the service hour, the proximity, and the frequency attributes are important and performed well in the years of COVID-19. On the other hand, the temperature and the cleanliness factors are not significant predictors of the PV and PT users’ general satisfaction. The obtained results can be used by local governments and authorities, who seek to identify areas to enhance the service quality of PT during movement restrictions in a pandemic wave.
Effect of environmental variance-based resilience selection on the gut metabolome of rabbits
Authors: Casto-Rebollo Cristina , Argente María José , García María Luz , Blasco Agustín , Ibáñez-Escriche Noelia
Published: March 2023

Background

Gut metabolites are key actors in host-microbiota crosstalk with effect on health. The study of the gut metabolome is an emerging topic in livestock, which can help understand its effect on key traits such as animal resilience and welfare. Animal resilience has now become a major trait of interest because of the high demand for more sustainable production. Composition of the gut microbiome can reveal mechanisms that underlie animal resilience because of its influence on host immunity. Environmental variance (VE), specifically the residual variance, is one measure of resilience. The aim of this study was to identify gut metabolites that underlie differences in the resilience potential of animals originating from a divergent selection for VE of litter size (LS). We performed an untargeted gut metabolome analysis in two divergent rabbit populations for low (n = 13) and high (n = 13) VE of LS. Partial least square-discriminant analysis was undertaken, and Bayesian statistics were computed to determine dissimilarities in the gut metabolites between these two rabbit populations.

Results

We identified 15 metabolites that discriminate rabbits from the divergent populations with a prediction performance of 99.2% and 90.4% for the resilient and non-resilient populations, respectively. These metabolites were suggested to be biomarkers of animal resilience as they were the most reliable. Among these, five that derived from the microbiota metabolism (3-(4-hydroxyphenyl)lactate, 5-aminovalerate, and equol, N6-acetyllysine, and serine), were suggested to be indicators of dissimilarities in the microbiome composition between the rabbit populations. The abundances of acylcarnitines and metabolites derived from the phenylalanine, tyrosine, and tryptophan metabolism were low in the resilient population and these pathways can, therefore impact the inflammatory response and health status of animals.

Conclusions

This is the first study to identify gut metabolites that could act as potential resilience biomarkers. The results support differences in resilience between the two studied rabbit populations that were generated by selection for VE of LS. Furthermore, selection for VE of LS modified the gut metabolome, which could be another factor that modulates animal resilience. Further studies are needed to determine the causal role of these metabolites in health and disease.
Improved computations for relationship inference using low-coverage sequencing data
Authors: Mostad Petter , Tillmar Andreas , Kling Daniel
Published: March 2023

Pedigree inference, for example determining whether two persons are second cousins or unrelated, can be done by comparing their genotypes at a selection of genetic markers. When the data for one or more of the persons is from low-coverage next generation sequencing (lcNGS), currently available computational methods either ignore genetic linkage or do not take advantage of the probabilistic nature of lcNGS data, relying instead on first estimating the genotype. We provide a method and software (see familias.name/lcNGS) bridging the above gap. Simulations indicate how our results are considerably more accurate compared to some previously available alternatives. Our method, utilizing a version of the Lander-Green algorithm, uses a group of symmetries to speed up calculations. This group may be of further interest in other calculations involving linked loci.
Genome-wide identification and expression analysis of the anthocyanin-related genes during seed coat development in six Brassica species
Authors: Chen Daozong , Chen Haidong , Dai Guoqiang , Zhang Haimei , Liu Yi , Shen Wenjie , Zhu Bo , Cui Cheng , Tan Chen
Published: March 2023

Yellow seed is one favorite trait for the breeding of Brassica oilseed crops, but the performance of seed coat color is very complicated due to the involvement of various pigments. The change of seed coat color of Brassica crops is related to the specific synthesis and accumulation of anthocyanin, and the expression level of structural genes in anthocyanin synthesis pathway is specifically regulated by transcription factors. Despite some previous reports on the regulations of seed coat color from linkage marker development, gene fine-mapping and multi-omics association analysis, the trait of Brassica crops is affected by the evolutionary events such as genome triploidization, the regulatory mechanism is still largely unknown. In this study, we identified genes related to anthocyanin synthesis in six Brassica crops in U-triangle at the genome-wide level and performed collinearity analysis. A total of 1119 anthocyanin-related genes were identified, the collinear relationship of anthocyanin-related genes on subgenomic chromosomes was the best in B. napus (AACC) and the worst in B. carinata (BBCC). The comparisons of gene expressions for anthocyanin metabolic pathways in seed coats during seed development revealed differences in its metabolism among these species. Interestingly, the R2R3-MYB transcription factors MYB5 and TT2 were differentially expressed at all eight stages of seed coat development, indicating that they might be the key genes that caused the variation of the seed coat color. The expression curve and trend analyses of the seed coat development period showed that the main reason for the unexpressed copies of MYB5 and TT2 was likely gene silencing caused by gene structural variation. These results were valuable for the genetic improvement of Brassica seed coat color, and also provided new insights into gene multicopy evolution in Brassica polyploids.
Identification and examination of nitrogen metabolic genes in Lelliottia amnigena PTJIIT1005 for their ability to perform nitrate remediation
Authors: Thakur Preeti , Gauba Pammi
Published: March 2023

Lelliottia amnigena PTJIIT1005 is a bacterium that utilizes nitrate as the sole nitrogen source and can remediate nitrate from media. The annotation was done related to nitrogen metabolic genes using the PATRIC, RAST tools, and PGAP from the genome sequence of this bacterium. Multiple sequence alignments and phylogenetic analysis of respiratory nitrate reductase, assimilatory nitrate reductase, nitrite reductase, glutamine synthetase, hydroxylamine reductase, nitric oxide reductase genes from PTJIIT1005 were done to find out sequence identities with the most similar species. The identification of operon arrangement in bacteria was also identified. The PATRIC KEGG feature mapped the N-metabolic pathway to identify the chemical process, and the 3D structure of representative enzymes was also elucidated. The putative protein 3D structure was analyzed using I-TASSER software. It gave good quality protein models of all nitrogen metabolism genes and showed good sequence identity with reference templates, approximately 81–99%, except for two genes; assimilatory nitrate reductase and nitrite reductase. This study suggested that PTJIIT1005 can remove N-nitrate from water because of having N-assimilation and denitrification genes.
Identification of inadequate responders to advanced therapy among commercially-insured adult patients with Crohn’s disease and ulcerative colitis in the United States
Authors: Gibble Theresa Hunter , Naegeli April N. , Grabner Michael , Isenberg Keith , Shan Mingyang , Teng Chia-Chen , Curtis Jeffrey R.
Published: March 2023

Background

The purpose of this analysis was to assess the frequency of inadequate response over 1 year from advanced therapy initiation among patients with Crohn’s disease (CD) or ulcerative colitis (UC) in the United States using a claims-based algorithm. Factors associated with inadequate response were also analyzed.

Methods

This study utilized claims data of adult patients from the HealthCore Integrated Research Database (HIRD®) from January 01, 2016 to August 31, 2019. Advanced therapies used in this study were tumor necrosis factor inhibitors (TNFi) and non-TNFi biologics. Inadequate response to an advanced therapy was identified using a claims-based algorithm. The inadequate response criteria included adherence, switching to/added a new treatment, addition of a new conventional synthetic immunomodulator or conventional disease-modifying drugs, increase in dose/frequency of advanced therapy initiation, and use of a new pain medication, or surgery. Factors influencing inadequate responders were assessed using multivariable logistic regression.

Results

A total of 2437 patients with CD and 1692 patients with UC were included in this analysis. In patients with CD (mean age: 41 years; female: 53%), 81% had initiated TNFi, and 62% had inadequate response. In patients with UC (mean age: 42 years; female: 48%), 78% had initiated a TNFi, and 63% had an inadequate response. In both patients with CD and UC, inadequate response was associated with low adherence (CD: 41%; UC: 42%). Inadequate responders were more likely to be prescribed a TNFi (for CD: odds ratio [OR] = 1.94;p < 0.001; for UC: OR = 2.76;p < 0.0001).

Conclusion

More than 60% of patients with CD or UC had an inadequate response to their index advanced therapy within 1 year after initiation, mostly driven by low adherence. This modified claims-based algorithm for CD and UC appears useful to classify inadequate responders in health plan claims data.
Characterisation of tumor microenvironment and prevalence of CD274/PD-L1 genetic alterations difference in colorectal Cancer
Authors: Yang Lin , Liu Shousheng , He Wenzhuo , Xiong Zhenchong , Xia Liangping
Published: March 2023

Background

Large-scale genomic alterations, especially CD274/PD-L1 gene amplification, have great impact on anti-PD-1 efficacy on cancers such as Hodgkin’s lymphoma. However, the prevalence of PD-L1 genetic alterations in colorectal cancer (CRC) and its correlation with the tumor immune microenvironment and clinical implications remain unknown.

Materials and Methods

PD-L1 genetic alterations were evaluated in 324 patients with newly diagnosed CRC including 160 mismatch repair-deficient (dMMR) patients and 164 mismatch repair-proficient (pMMR) patients using fluorescence in situ hybridization (FISH) method. The correlation between PD-L1 and the expression of the common immune markers was analyzed.

Results

Totally 33 (10.2%) patients were identified with aberrant PD-L1 genetic alternations including deletion (2.2%), polysomy (4.9%), and amplification (3.1%); They had more aggressive features such as advanced stage (P = 0.02), shorter overall survival (OS) (P < 0.001) than patients with disomy. The aberrations correlated with positive lymph node (PLN) (p = 0.001), PD-L1 expression by immunohistochemistry (IHC) in tumor cells (TCs) or tumor-infiltrated immunocytes (ICs) (both p < 0.001), and pMMR (p = 0.029). When dMMR and pMMR were analyzed independently, the correlations of aberrant PD-L1 genetic alterations with PD-1 expression (p = 0.016), CD4 + T cells (p = 0.032), CD8 T + cells (p = 0.032) and CD68 + cells (p = 0.04) were only found in dMMR cohort.

Conclusions

The prevalence of PD-L1 genetic alterations was relatively low in CRC, but the aberrations usually correlate with aggressive nature. The correlation between PD-L1 genetic alterations and tumor immune features was only observed in dMMR CRC.
The hsa_circ_0000276-ceRNA regulatory network and immune infiltration in cervical cancer
Authors: Zhang Honglei , Wang Xiuting , Li Yaqin , Bai Ying , Li Qi , Wang Shuling , Wei Yimiao , Li Jiarong , Wen Songquan , Zhao Weihong
Published: March 2023

Background

Our previous studies have confirmed that miR-154-5p can regulate pRb expression, and thus, play a tumor suppressor role in HPV16 E7-induced cervical cancer. However, its upstream molecules have not been elucidated in the progression of cervical cancer. This study aimed to explore the role of the miR-154-5p upstream molecule, hsa_circ_0000276 in cervical cancer development and its possible mechanisms of action.

Methods

We detected differences in whole transcriptome expression profiles of cervical squamous carcinoma and tissues adjacent to cervical cancer tissues from patients using microarray technology to predict circular RNAs (circRNAs) with binding sites to miR-154-5p. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression of hsa_circ_0000276 (which had the strongest binding capacity to miR-154 and was selected as the target molecule) in cervical cancer tissues, followed by in vitro functional assays. Downstream microRNAs (miRNAs) and mRNAs of hsa_circ_0000276 were identified using transcriptome microarray data and databases, while the protein–protein interaction networks were obtained using STRING. A competing endogenous RNA (ceRNA) network centered on hsa_circ_0000276 was constructed using Cytoscape and GO and KEGG databases. Abnormal expression and prognosis of critical downstream molecules were analyzed using gene databases and molecular experiments. qRT-PCR and western blot analysis was performed to verify the expression of candidate genes.

Results

We identified 4,001 differentially expressed circRNAs between HPV16-positive cervical squamous carcinoma and benign cervical tissues and 760 circRNAs targeting miR-154-5p, including hsa_circ_0000276. hsa_circ_0000276 and miR-154-5p directly bound, and hsa_circ_0000276 was upregulated, in cervical precancerous lesions and cervical cancer tissues and cells. Silencing hsa_circ_0000276 inhibited G1/S transition and cell proliferation and promoted apoptosis in SiHa and CaSki cells. Bioinformatics analysis showed that the hsa_circ_0000276 ceRNA network included 17 miRNAs and seven mRNAs, and downstream molecules of hsa_circ_0000276 were upregulated in cervical cancer tissues. These downstream molecules were associated with a poor prognosis and affected cervical cancer-associated immune infiltration. Of these, expression of CD47, LDHA, PDIA3, and SLC16A1 was downregulated in sh_hsa_circ_0000276 cells.

Conclusions

Our findings show that hsa_circ_0000276 exerts cancer-promoting effects in cervical cancer and is an underlying biomarker for cervical squamous cell carcinoma.
Spatial characterization and quantification of CD40 expression across cancer types
Authors: Bates Katherine M. , Vathiotis Ioannis , MacNeil Tyler , Ahmed Fahad Shabbir , Aung Thazin Nwe , Katlinskaya Yuliya , Bhattacharya Sabyasachi , Psyrri Amanda , Yea Steven , Parkes Amanda , Sadraei Nooshin Hashemi , Roychoudhury Siddhartha , Rimm David L. , Gavrielatou Niki
Published: March 2023

Background

CD40, a TNF receptor family member, is expressed by a variety of immune cells and is involved in the activation of both adaptive and innate immune responses. Here, we used quantitative immunofluorescence (QIF) to evaluate CD40 expression on the tumor epithelium of solid tumors in large patient cohorts of lung, ovarian, and pancreatic cancers.

Methods

Tissue samples from nine different solid tumors (bladder, breast, colon, gastric, head and neck, non-small cell lung cancer (NSCLC), ovarian, pancreatic and renal cell carcinoma), constructed in tissue microarray format, were initially assessed for CD40 expression by QIF. CD40 expression was then evaluated on the large available patient cohorts for three of the tumor types demonstrating high CD40 positivity rate; NSCLC, ovarian and pancreatic cancer. The prognostic impact of CD40 expression on tumor cells was also investigated.

Results

CD40 expression on tumor cells was found to be common, with 80% of the NSCLC population, 40% of the ovarian cancer population, and 68% of the pancreatic adenocarcinoma population displaying some degree of CD40 expression on cancer cells. All of three of these cancer types displayed considerable intra-tumoral heterogeneity of CD40 expression, as well as partial correlation between expression of CD40 on tumor cells and on surrounding stromal cells. CD40 was not found to be prognostic for overall survival in NSCLC, ovarian cancer, or pancreatic adenocarcinoma.

Conclusions

The high percentage of tumor cells expressing CD40 in each of these solid tumors should be considered in the development of therapeutic agents designed to target CD40.
Association between sedentary behavior and depression in US adults with chronic kidney disease: NHANES 2007–2018
Authors: Liu Lin , Yan Yuqin , Qiu Jingxian , Chen Qiongmei , Zhang Yujing , Liu Yun , Zhong Xiaoshi , Liu Yan , Tan Rongshao
Published: March 2023

Background

Depression increases the risk of adverse clinical outcomes in patients with chronic kidney disease. Physical activity has been shown to improve depressive symptoms in this population, but the relationship of sedentary behavior with depression has not been studied. In this study, we examined the relationship between sedentary behavior and depression in patients with chronic kidney disease.

Methods

This cross-sectional study included 5,205 participants aged ≥ 18 years with chronic kidney disease participating in the 2007–2018 National Health and Nutrition Examination Survey. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9). Recreation activity, work activity, walking or cycling for transportation, and sedentary behavior were measured using the Global Physical Activity Questionnaire. A series of weighted logistic regression models were used to investigate the aforementioned relationship.

Results

The prevalence of depression among US adults with chronic kidney disease was 10.97% in our study. In addition, sedentary behavior was strongly associated with higher levels of depressive symptoms, as measured by the PHQ-9 (P < 0.001). In the fully adjusted model, we found that compared with participants who had shorter durations of sedentary behavior, participants who had the highest durations of sedentary behavior had 1.69 times (odd ratio 1.69, 95% confidence interval: 1.27, 2.24) greater risk of being clinically depressed. After adjusting for confounding factors, subgroup analyses showed that the association between sedentary behavior and depression still existed in all stratifications.

Conclusion

We found an association between longer duration of sedentary behavior and more severe depression in US adults with chronic kidney disease; however, prospective studies with larger sample sizes are still needed to confirm the effects of sedentary behavior on depression in the chronic kidney disease population.
Prevalence of potentially traumatic events and symptoms of depression, anxiety, hazardous alcohol use, and post-traumatic stress disorder among people with HIV initiating HIV care in Cameroon
Authors: Parcesepe Angela M. , Filiatreau Lindsey M. , Ebasone Peter Vanes , Dzudie Anastase , Pence Brian W. , Wainberg Milton , Yotebieng Marcel , Anastos Kathryn , Pefura-Yone Eric , Nsame Denis , Ajeh Rogers , Nash Denis
Published: March 2023

Background

This study explored the relationship between specific types of potentially traumatic events (PTEs) and symptoms of mental health disorders among people with HIV (PWH) in Cameroon.

Methods

We conducted a cross-sectional study with 426 PWH in Cameroon between 2019–2020. Multivariable log binominal regression was used to estimate the association between exposure (yes/no) to six distinct types of PTE and symptoms of depression (Patient Health Questionnaire-9 score > 9), PTSD (PTSD Checklist for DSM-5 score > 30), anxiety (Generalized Anxiety Disorder-7 scale score > 9), and hazardous alcohol use (Alcohol Use Disorders Identification Test score > 7 for men; > 6 for women).

Results

A majority of study participants (96%) reported exposure to at least one PTE, with a median of 4 PTEs (interquartile range: 2–5). The most commonly reported PTEs were seeing someone seriously injured or killed (45%), family members hitting or harming one another as a child (43%), physical assault or abuse from an intimate partner (42%) and witnessing physical assault or abuse (41%). In multivariable analyses, the prevalence of PTSD symptoms was significantly higher among those who reported experiencing PTEs during childhood, violent PTEs during adulthood, and the death of a child. The prevalence of anxiety symptoms was significantly higher among those who reported experiencing both PTEs during childhood and violent PTEs during adulthood. No significant positive associations were observed between specific PTEs explored and symptoms of depression or hazardous alcohol use after adjustment.

Conclusions

PTEs were common among this sample of PWH in Cameroon and associated with PTSD and anxiety symptoms. Research is needed to foster primary prevention of PTEs and to address the mental health sequelae of PTEs among PWH.
Adolescence internalizing problems as a mediator between autism diagnosis in childhood and quality of life in emerging adults with and without autism: a 10-year longitudinal study
Authors: Andersen Per Normann , Orm Stian , Fossum Ingrid Nesdal , Øie Merete Glenne , Skogli Erik Winther
Published: March 2023

Background

Individuals with autism tend to have a reduced quality of life across their lifespan. This reduced quality of life may be a result of autism traits, mental distress, and poor person/environment fit. In this longitudinal study, we looked at the role of adolescence internalizing and externalizing problems in mediating the relationship between having an autism diagnosis from childhood and perceived quality of life as emerging adults.

Methods

A total of 66 participants in a group of emerging adults with autism (mean age 22.2 years), and without autism (mean age 20.9 years) were assessed in three assessment waves (T1 at 12 years, T2 at 14 years, and T3 at 22 years of age). Parents filled out the Child Behavior Checklist at T2 and participants filled out the Perceived Quality of Life Questionnaire at T3. Total and indirect effects were tested in serial mediation analysis.

Results

The results showed that internalizing problems fully mediated the association between childhood autism diagnosis and the quality of life in emerging adulthood, while externalizing problems did not.

Conclusion

Our findings suggest that attention to adolescent internalizing problems is important to improve the later quality of life for emerging adults with autism.
Primary hyperparathyroidism in young patients is associated with metabolic disorders: a prospective comparative study
Authors: Bibik Ekaterina E. , Dobreva Ekaterina A. , Elfimova Alina R. , Miliutina Anastasiia P. , Eremkina Anna K. , Gorbacheva Anna M. , Krupinova Julia A. , Koksharova Ekaterina O. , Sklyanik Igor A. , Mayorov Alexander Y. , Mokrysheva Natalia G.
Published: March 2023

Background

Components of metabolic syndrome can be observed in patients with primary hyperparathyroidism (PHPT). The link between these disorders remains unclear due to the lack of relevant experimental models and the heterogeneity of examined groups. The effect of surgery on metabolic abnormalities is also controversial. We conducted a comprehensive assessment of metabolic parameters in young patients with PHPT.

Methods

One-center prospective comparative study was carried out. The participants underwent a complex biochemical and hormonal examination, a hyperinsulinemic euglycemic and hyperglycemic clamps, a bioelectrical impedance analysis of the body composition before and 13 months after parathyroidectomy compared to sex-, age- and body mass index matched healthy volunteers.

Results

45.8% of patients (n = 24) had excessive visceral fat. Insulin resistance was detected in 54.2% of cases. PHPT patients had higher serum triglycerides, lower M-value and higher C-peptide and insulin levels in both phases of insulin secretion compared to the control group (p < 0.05 for all parameters). There were tendencies to decreased fasting glucose (p = 0.031), uric acid (p = 0.044) and insulin levels of the second secretion phase (p = 0.039) after surgery, but no statistically significant changes of lipid profile and M-value as well as body composition were revealed. We obtained negative correlations between percent body fat and osteocalcin and magnesium levels in patients before surgery.

Conclusion

PHPT is associated with insulin resistance that is the main risk factor of serious metabolic disorders. Surgery may potentially improve carbohydrate and purine metabolism.
Prevalence of anemia and its associated factors among patients with type 2 diabetes mellitus in a referral diabetic clinic in the north of Iran
Authors: Hizomi Arani Reyhane , Fakhri Farima , Naeimi Tabiee Mohammad , Talebi Fatemeh , Talebi Zahra , Rashidi Negin , Zahedi Maryam
Published: March 2023

Background

Purpose

This study intended to investigate the prevalence of anemia and its associated factors among patients with type 2 diabetes mellitus (T2DM) in Gorgan, Iran.

Methods

This cross-sectional study was conducted on 415 (109 men) patients with T2DM referred to the referral diabetes clinic of Sayad Shirazi Hospital in Gorgan in 2021. Demographic information, anthropometric indices, past medical history,  and some laboratory data on cell counts, serum blood glucose, HbA1c, creatinine, lipid/iron profiles, and urinary albumin were collected. The univariable and multivariable logistic regression analysis was applied to compute odds ratios (ORs) and 95% confidence intervals (CI) for potential associated factors, using SPSS version 21. The multivariable Model was adjusted for obesity, Hb A1c, T2DM duration, using glucose-lowering drugs (GLDs), chronic kidney disease (CKD), albuminuria, hypertriglyceridemia, and hypercholesterolemia. 

Results

The prevalence of anemia was 21.5% [95%CI: 17.6-25.7] among our total participants. The corresponding values for men and women were 20.2 (13.1-29.0) and 21.9 (17.4-27.0), respectively.The adjusted model revealed that obesity (OR, 1.94 [95% CI, 1.17–3.23]), T2DM duration for more than five years (OR, 3.12 [1.78–5.47]), albuminuria (OR, 6.37 [3.13–10.91]), chronic kidney disease (OR, 4.30 [ 2.83–7.29]) and hypertriglyceridemia (OR, 1.72 [ 1.21–2.77]) were significantly associated with prevalent anemia among patients with T2DM. Moreover, using insulin separately or in combination with oral GLDs associated positively with the prevalence of anemia with ORs of 2.60 [1.42-6.42] and 1.87 [1.30-4.37] , respectively.

Conclusion

Anemia had a high prevalence among patients with T2DM in the north of Iran (about 22%), which is associated with obesity, hypertriglyceridemia, duration of T2DM, and diabetic kidney disease.
Living through uncertainty: a qualitative study on leadership and resilience in primary healthcare during COVID-19
Authors: Karreinen Soila , Paananen Henna , Kihlström Laura , Janhonen Kristiina , Huhtakangas Moona , Viita-aho Marjaana , Tynkkynen Liina-Kaisa
Published: March 2023

Background

Resilience is often referred to when assessing the ability of health systems to maintain their functions during unexpected events. Primary healthcare forms the basis for the health system and thus its resilient responses are vital for the outcomes of the whole system. Understanding how primary healthcare organisations are able to build resilience before, during, and after unexpected or sudden shocks, is key to public health preparedness. This study aims to identify how leaders responsible for local health systems interpreted changes in their operational environment during the first year of COVID-19, and to elucidate how these views reflect aspects of resilience in healthcare.

Methods

The data consist of 14 semi-structured individual interviews with leaders of local health systems in Finland representing primary healthcare. The participants were recruited from four regions. An abductive thematic analysis was used to identify entities from the viewpoints of the purpose, resources, and processes of resilience in the healthcare organisation.

Results

Results were summarised as six themes, which suggest that embracing uncertainty is viewed by the interviewees a basis for primary healthcare functioning. Leading towards adaptability was regarded a distinct leadership task enabling the organisation to modify its functions according to demands of the changing operational environment. Workforce, knowledge and sensemaking, as well as collaboration represented what the leaders viewed as the means for achieving adaptability. The ability to adapt functioned to comprehensively meet the population’s service needs built on a holistic approach.

Conclusions

The results showed how the leaders who participated in this study adapted their work during changes brought on by the pandemic, and what they viewed as critical for maintaining organisational resilience. The leaders considered embracing uncertainty as a principal feature of their work rather than viewing uncertainty as aberrant and something to avoid. These notions, along with what the leaders considered as critical means for building resilience and adaptability should be addressed and elaborated in future research. Research on resilience and leadership should be conducted more in the complex context of primary healthcare, where cumulative stresses are encountered and processed continuously.