bluuebunny/crossref_metadata_2025 huggingface dataset:
Malaria care-seeking and treatment ideation among gold miners in Guyana
Authors: Olapeju Bolanle , Adams Camille , Wilson Sean , Simpson Joann , Hunter Gabrielle C. , Davis TrishAnn , Mitchum Lyndsey , Cox Horace , James Kashana , Orkis Jennifer , Storey J. Douglas
Published: January 2022

Background

Although miners are a priority population in malaria elimination in Guyana, scant literature exists on the drivers of malaria-related behaviour. This study explores the relationship between gold miners’ malaria-related ideation and the adoption of malaria care-seeking and treatment behaviours including prompt care-seeking, malaria testing, and self-medication.

Methods

Data are from a cross-sectional quantitative survey of 1685 adult miners between the ages of 18–59 years who live in mining camps in Regions 1, 7, and 8. The analysis focused on miners who reported an episode of fever in the past year (n = 745). Malaria care-seeking and treatment ideation was defined as a composite additive score consisting of the following variables: general malaria knowledge, perceived severity, perceived susceptibility, beliefs, perceived self-efficacy, perceived norms, interpersonal communication, and perceived response efficacy. Multivariable logistic regressions explored the relationship between ideation on care-seeking/treatment behaviours, controlling for confounding variables.

Results

Most miners with a recent episode of fever had perceived risk (92%), self-efficacy (67%), susceptibility (53%) and high malaria knowledge (53%). Overall, miners' care-seeking/treatment ideation score ranged from 0 to 8 with a mean of 4.1. Ideation scores were associated with higher odds of care-seeking for fever (aOR: 1.19; 95% CI 1.04–1.36), getting tested for malaria (aOR: 1.22; 95% CI 1.07–1.38) and lower odds of self-medication (aOR: 0.87; 95% CI 0.77–0.99).

Conclusions

A national community case management initiative is using study findings as part of its scale-up, using volunteers to make testing and treatment services more accessible to miners. This is complemented by a multi-channel mass media campaign to improve miners’ ideation. Communication messages focus on increasing miners’ knowledge of malaria transmission and symptoms, encourage positive beliefs about malaria testing and volunteer testers, promote evidence about the effectiveness of testing, and reminders of how quick and easy it is to get a malaria test with the community case management initiative. Study findings also have implications for efforts to eliminate malaria across the Guiana Shield.
Impact of increasing the relative availability of meat-free options on food selection: two natural field experiments and an online randomised trial
Authors: Pechey Rachel , Bateman Paul , Cook Brian , Jebb Susan A.
Published: January 2022

Background

Increasing the availability of lower energy-density foods is a promising intervention to encourage healthier food purchasing but few studies have examined the effect of increasing availability of meat-free meals to promote more sustainable purchasing. We report three studies, all examining the impact of altering the availability of meat-free meals on meal selection.

Methods

Study 1 (a natural experiment in one university cafeteria) examined the impact of altering the ratio of meat-free meals (one meat-free and two meat, to two meat-free and one meat) on weekly sales of meals containing meat. Study 2 (a natural experiment in 18 worksite cafeterias) examined the impact on meat-free meal sales of a menu change designed to increase the availability of meat-free meals. Study 3 (an online study of 2205 UK-representative adults) compared meal selections when participants were randomised to ranges comprised of (a) one meat-free, three meat options; (b) two meat-free, two meat; or (c) three meat-free, one meat.

Results

Study 1 suggested a significant decrease in the proportion of sales of meat options when the availability of meat-free options increased (− 19.9 percentage points; 95%CIs:-25.2,-14.6), with no evidence of changes to meat-based meal sales in other university cafeterias during the same period. Findings from Study 2 were mixed: multilevel regressions found no evidence of an increase in meat-free meals following the menu change (2.3 percentage points; 95%CIs: − 1.3,5.9), while interrupted time-series analyses suggested sales did increase (2.3; 95%CIs: 0.4,4.2), but implementation of the planned change was limited. In Study 3 reducing meat-free options from 50 to 25% reduced participants’ selection of meat-free options (odds ratio 0.35; 95%CIs: 0.26,0.46), while increasing meat-free options from 50 to 75% increased meat-free selections (odds ratio 2.43; 95%CIs: 1.94,3.04). There was no evidence effects were moderated by gender, socioeconomic status or usual meat consumption.

Conclusion

Increasing the availability of meat-free options is effective at reducing meat selection and purchasing for different ratios of meat to meat-free options. The magnitude of the effect is uncertain, but with no evidence of differences in response by demographic groups when directly tested.

Trial registration

Study 3: Open Science Framework; https://osf.io/ze9c6; 6/8/2020.
Barriers and facilitators to implementation of direct fruit and vegetables provision interventions in kindergartens and schools: a qualitative systematic review applying the consolidated framework for implementation research (CFIR)
Authors: Meshkovska Biljana , Scheller Daniel A. , Wendt Janine , Jilani Hannah , Scheidmeir Marie , Stratil Jan M. , Lien Nanna ,   on behalf of the PEN Consortium
Published: January 2022

Background

Although children’s intake of fruit and vegetables has seen a recent rise, almost half of adolescents do not eat even one piece of fruit or vegetables per day. One way to address this problem is through interventions that provide fruit and vegetables directly to children in kindergartens and schools. For such interventions to meet their intended goals, what is important to consider in addition to impact is implementation. Our objective is to systematically review qualitative results reporting on the determinants (barriers and facilitators) to implementation of interventions that entail direct provision of fruit and vegetables in kindergarten and school settings and conduct a framework analysis of those results using the Consolidated Framework for Implementation Research (CFIR).

Methods

A systematic search was designed and run in November 2019 for: MEDLINE (Ovid), Embase (Ovid), PsychINFO (Ovid), ERIC (Ovid), Cochrane Library Reviews and Cochrane Library Trials. A keyword search of the journal Implementation Science was completed. Screening of titles and abstracts (n = 5427) and full texts (n = 227), led to 14 included articles. Coding and analysis were done using the framework method and CFIR.

Results

The following CFIR constructs were found relevant: 1) intervention characteristics domain: ‘design quality and packaging’, ‘adaptability’ ‘cost’; 2) outer setting: ‘cosmopolitanism’, ‘external policy and incentives’ ‘patients’ needs and resources’; 3) inner setting: ‘implementation climate’, ‘readiness for implementation’ and ‘structural characteristics’; 4) characteristics of individuals: ‘individual stage of change’, ‘knowledge and beliefs about the intervention’ 5) process: ‘engaging’, ‘executing’ and ‘reflecting and evaluating’. The review stresses the dual role of parents as both supporting the implementation and targets of the intervention, which could have implications for the design and implementation of future fruit and vegetables interventions. Positive child perceptions of the value of the intervention and perceived behavior change due to the intervention were reported as relevant facilitators to implementation across several studies, and should be taken into consideration in future design efforts.

Conclusions

CFIR offers a systematic way to identify and organize barriers and facilitators to implementation of interventions in the kindergarten and school setting. Revisions are encouraged to allow adequate space for perceptions of various implementation actors and the target group.

PROSPERO registration

CRD42020167697.
Circular RNA circCSPP1 promotes the occurrence and development of colon cancer by sponging miR-431 and regulating ROCK1 and ZEB1
Authors: Wang Jin , Zhou Lei , Chen Bingxin , Yu Zhuwen , Zhang Jianglei , Zhang Zhe , Hu Chenrui , Bai Yanjin , Ruan Xiaokang , Wang Shengjia , Ouyang Jun , Wu Airong , Zhao Xin
Published: January 2022

Background

Colon cancer is a common malignant tumor of the digestive tract, and its incidence is ranked third among gastrointestinal tumors. The present study aims to investigate the role of a novel circular RNA (circCSPP1) in colon cancer and its underlying molecular mechanisms.

Methods

Bioinformatics analysis and reverse transcription-quantitative PCR were used to detect the expression levels of circCSPP1 in colon cancer tissues and cell lines. The effects of circCSPP1 on the behavior of colon cancer cells were investigated using CCK-8, transwell and clonogenic assays. Bioinformatics analysis along with luciferase, fluorescence in situ hybridization and RNA pull-down assays were used to reveal the interaction between circCSPP1, microRNA (miR)-431, Rho associated coiled-coil containing protein kinase 1 (ROCK1) and zinc finger E-box binding homeobox 1 (ZEB1).

Results

It was found that circCSPP1 expression was significantly upregulated in colon cancer tissues and cell lines. Overexpression of circCSPP1 significantly promoted the proliferation, migration and invasion of colon cancer cells, whereas silencing of circCSPP1 exerted opposite effects. Mechanistically, circCSPP1 was found to bind with miR-431. In addition, ROCK1 and ZEB1 were identified as the target genes of miR-431. Rescue experiments further confirmed the interaction between circCSPP1, miR-431, ROCK1 and ZEB1. Moreover, circCSPP1 promoted the expression level of ROCK1, cyclin D1, cyclin-dependent kinase 4, ZEB1 and Snail, and lowered the E-cadherin expression level.

Conclusion

Taken together, the findings of the present study indicated that circCSPP1 may function as a competing endogenous RNA in the progression of colon cancer by regulating the miR-431/ROCK1 and miR-431/ZEB1 signaling axes.
YTHDC1 regulates distinct post-integration steps of HIV-1 replication and is important for viral infectivity
Authors: N’Da Konan Sarah , Ségéral Emmanuel , Bejjani Fabienne , Bendoumou Maryam , Ait Said Mélissa , Gallois-Montbrun Sarah , Emiliani Stéphane
Published: January 2022

Background

The recent discovery of the role of m6A methylation in the regulation of HIV-1 replication unveiled a novel layer of regulation for HIV gene expression. This epitranscriptomic modification of HIV-1 RNAs is under the dynamic control of specific writers and erasers. In addition, cytoplasmic readers of the m6A mark are recruited to the modified viral RNAs and regulate HIV-1 replication. Yet, little is known about the effects of m6A writers and readers on the biogenesis of HIV-1 RNAs.

Results

We showed that the METTL3/14 m6A methyltransferase complex and the m6A YTHDF2 cytoplasmic reader down regulates the abundance of HIV-1 RNAs in infected cells. We also identified the m6A nuclear reader YTHDC1 as a novel regulator of HIV-1 transcripts. In HIV-1 producer cells, we showed that knocking down YTHDC1 increases the levels of unspliced and incompletely spliced HIV-1 RNAs, while levels of multiply spliced transcripts remained unaffected. In addition, we observed that depletion of YTHDC1 has no effect on the nuclear cytoplasmic distribution of viral transcripts. YTHDC1 binds specifically to HIV-1 transcripts in a METTL3-dependent manner. Knocking down YTHDC1 reduces the expression of Env and Vpu viral proteins in producer cells and leads to the incorporation of unprocessed Env gp160 in virus particles, resulting in the decrease of their infectivity.

Conclusions

Our findings indicate that, by controlling HIV-1 RNA biogenesis and protein expression, the m6A nuclear reader YTHDC1 is required for efficient production of infectious viral particles.

Graphical Abstract
Assessing the effects of mining projects on child health in sub-Saharan Africa: a multi-country analysis
Authors: Cossa Hermínio , Dietler Dominik , Macete Eusébio , Munguambe Khátia , Winkler Mirko S. , Fink Günther
Published: January 2022

Background

The African continent hosts many industrial mining projects, and many more are planned due to recent prospecting discoveries and increasing demand for various minerals to promote a low-carbon future. The extraction of natural resources in sub-Saharan Africa (SSA) represents an opportunity for economic development but also poses a threat to population health through rapid urbanisation and environmental degradation. Children could benefit from improved economic growth through various channels such as access to high-quality food, better sanitation, and clean water. However, mining can increase food insecurity and trigger local competition over safe drinking water. Child health can be threatened by exposure to mining-related air, noise, and water pollution. To assess the impact of mines on child health, we analyse socio-demographic, health, and mining data before and after several mining projects were commissioned in SSA.

Results

Data of 90,951 children living around 81 mining sites in 23 countries in SSA were analysed for child mortality indicators, and 79,962 children from 59 mining areas in 18 SSA countries were analysed for diarrhoea, cough, and anthropometric indicators. No effects of the launch of new mining projects on overall under-five mortality were found (adjusted Odds Ratio (aOR): 0.88; 95% Confidence Interval (CI): 0.68–1.14). However, activation of mining projects reduced the mortality risk among neonates (0–30 days) by 45% (aOR: 0.55; 95% CI: 0.37–0.83) and risk for a child to develop diarrhoeal diseases by 32% (aOR: 0.68; 95% CI: 0,51–0.90). The timing analysis of observed changes showed that there is a significant decline in the risk for childhood diarrhoea (aOR: 0.69; 95% CI: 0.49–0.97), and the mean height-for-age z-scores by 28 percentage points, during the prospection and construction phase; i.e., within four years to the initiation of extraction activity. No effects were found for cough and weight-for-height.

Conclusion

The results presented suggest that the impacts of mining on child health vary throughout the mine’s life cycle. Mining development likely contributes positively to the income and livelihoods of the impacted communities in the initial years of mining operations, particularly the prospection and construction phase; these potential benefits are likely to be at least partially offset by food insecurity and environmental pollution during early and later mining stages, respectively. Further research is warranted to better understand these health impacts and to identify policies that can help sustain the positive initial health impacts of mining projects in the long term.
The impact of CARA mandates on nurse practitioner controlled substance prescribing in Oregon: a cohort study
Authors: Klein Tracy A. , Hartung Daniel , Markwardt Sheila
Published: January 2022

Background

In 2017, the United States Comprehensive Addiction and Recovery Act (CARA) expanded authorization to prescribe buprenorphine for opioid use disorder (OUD) to nurse practitioners (NPs). Compared to physicians, NPs were required to complete 16 additional hours of training on controlled substance prescribing before a buprenorphine waiver application. As this differential additional education mandate was seen as a potential barrier, we evaluated the impact of this requirement on both NP waiver acquisition and prescribing of controlled substances, comparing NPs who obtained waivers to those who had not.

Methods

Through 2016–2018 Oregon Prescription Drug Monitoring Program and linked NP licensure data, we identified factors associated with waiver acquisition at baseline (2016) and evaluated changes in controlled substance prescribing before (2016) and after waiver acquisition (2018). Using chi-square and Mann-Whitney U testing, we calculated and described controlled substance prescribing types, rates, and patient level quantities including co-prescribing of benzodiazepines and opioids by NPs. Multivariable linear regression compared prescribing by waivered and non-waivered NPs for significant changes in non-buprenorphine controlled substance prescribing.

Results

Waivered NPs were more likely to have a psychiatric certification, have prior disciplinary action, and have generally higher levels of non-buprenorphine controlled substance prescribing than their non-waivered counterparts. While there was a significant increase in opioid prescriptions per patient among waivered NPs, following CARA implementation, co-prescribing of benzodiazepines and opioids significantly declined among waivered NPs relative to non-waivered NPs.

Conclusions

Although educational requirements were rescinded in 2021 for most applicants, enhanced opioid prescribing training should be incorporated into professional educational offerings regardless of regulatory mandate. We recommended continued focus on education regarding avoidance of high risk prescribing such as co-prescribing of opioids and benzodiazepines. NPs who acquire waivers may take on higher risk patients already using opioids, and these findings may represent transitions in practice and patient setting.
Addressing health disparities through implementation science—a need to integrate an equity lens from the outset
Authors: Kerkhoff Andrew D. , Farrand Erica , Marquez Carina , Cattamanchi Adithya , Handley Margaret A.
Published: January 2022

There is increasing attention being given to opportunities and approaches to advance health equity using implementation science. To reduce disparities in health, it is crucial that an equity lens is integrated from the earliest stages of the implementation process. In this paper, we outline four key pre-implementation steps and associated questions for implementation researchers to consider that may help guide selection and design of interventions and associated implementation strategies that are most likely to reach and be effective in reducing health disparities among vulnerable persons and communities.
Dosimetric impact of deep learning-based CT auto-segmentation on radiation therapy treatment planning for prostate cancer
Authors: Kawula Maria , Purice Dinu , Li Minglun , Vivar Gerome , Ahmadi Seyed-Ahmad , Parodi Katia , Belka Claus , Landry Guillaume , Kurz Christopher
Published: January 2022

Background

The evaluation of automatic segmentation algorithms is commonly performed using geometric metrics. An analysis based on dosimetric parameters might be more relevant in clinical practice but is often lacking in the literature. The aim of this study was to investigate the impact of state-of-the-art 3D U-Net-generated organ delineations on dose optimization in radiation therapy (RT) for prostate cancer patients.

Methods

A database of 69 computed tomography images with prostate, bladder, and rectum delineations was used for single-label 3D U-Net training with dice similarity coefficient (DSC)-based loss. Volumetric modulated arc therapy (VMAT) plans have been generated for both manual and automatic segmentations with the same optimization settings. These were chosen to give consistent plans when applying perturbations to the manual segmentations. Contours were evaluated in terms of DSC, average and 95% Hausdorff distance (HD). Dose distributions were evaluated with the manual segmentation as reference using dose volume histogram (DVH) parameters and a 3%/3 mm gamma-criterion with 10% dose cut-off. A Pearson correlation coefficient between DSC and dosimetric metrics, i.e. gamma index and DVH parameters, has been calculated.

Results

3D U-Net-based segmentation achieved a DSC of 0.87 (0.03) for prostate, 0.97 (0.01) for bladder and 0.89 (0.04) for rectum. The mean and 95% HD were below 1.6 (0.4) and below 5 (4) mm, respectively. The DVH parameters, V$$_{60/65/70\,{\mathrm{Gy}}}$$

60
/
65
/
70

Gy

for the bladder and V$$_{50/65/70\,{\mathrm{Gy}}}$$

50
/
65
/
70

Gy

for the rectum, showed agreement between dose distributions within $$\pm \, 5\%$$

±

5
%

and $$\pm \,2\%$$

±

2
%

, respectively. The D$$_{98/2\%}$$

98
/
2
%

and V$$_{95\%}$$

95
%

, for prostate and its 3 mm expansion (surrogate clinical target volume) showed agreement with the reference dose distribution within 2% and 3 Gy with the exception of one case. The average gamma pass-rate was 85%. The comparison between geometric and dosimetric metrics showed no strong statistically significant correlation.

Conclusions

The 3D U-Net developed for this work achieved state-of-the-art geometrical performance. Analysis based on clinically relevant DVH parameters of VMAT plans demonstrated neither excessive dose increase to OARs nor substantial under/over-dosage of the target in all but one case. Yet the gamma analysis indicated several cases with low pass rates. The study highlighted the importance of adding dosimetric analysis to the standard geometric evaluation.
Chondral injuries in patients with recurrent patellar dislocation: a systematic review
Authors: Migliorini Filippo , Marsilio Emanuela , Oliva Francesco , Eschweiler Jörg , Hildebrand Frank , Maffulli Nicola
Published: January 2022

Background

Patellar dislocations in patients presenting with recurrent patellofemoral instability can damage the surrounding structures, limiting patient’s participation to recreational activities and quality of life. This study evaluated frequency, location, and extent of associated injuries in patients with recurrent patellar dislocation.

Methods

This systematic review was conducted according to the PRISMA checklist. PubMed, Google scholar, Embase, and Web of Science databases were accessed in July 2021. All the published clinical studies reporting frequency, location, and extent of soft tissue lesions in patients with recurrent patellar dislocations were accessed.

Results

Data from 9 articles (232 patients) were retrieved. The mean age of the included patients was 21.2 ± 5.6 years. 84.8% of patients suffering from recurrent patellar dislocations demonstrated patellar chondral defects: medial facet (34.9%), while patellar crest (34.8%) and lateral facet (17%). 27.8% of patients demonstrated trochlear chondral injuries.

Conclusion

Chondral defects of the medial facet and the crest of the patella are the most common in patients with recurrent patellofemoral instability.
Cancer among syrian refugees living in Konya Province, Turkey
Authors: Kutluk Tezer , Koç Mehmet , Öner İrem , Babalıoğlu İbrahim , Kirazlı Meral , Aydın Sinem , Ahmed Fahad , Köksal Yavuz , Tokgöz Hüseyin , Duran Mustafa , Sullivan Richard
Published: January 2022

Background

With more than 3.6 million Syrian refugees Turkey hosts the world's largest number of Syrians. Considering the morbidity, mortality, and healthcare spending, cancer is one of the leading health and economic burden for patients and healthcare systems. However, very limited information available in the scientific literature to understand the burden and characteristics of cancer in countries hosting Syrian refugees. The aim of the present study is to evaluate the demographic and clinical characteristics, treatment outcome of Syrian cancer patients living in Konya, Turkey.

Methods

We retrospectively reviewed medical records of Syrian cancer patients at three major institutions from 2005 to 2020. The information regarding demographic and clinical characteristics of patients were identified. The number of days between the first symptom and diagnosis was considered as the “diagnostic interval”. Patients who failed to attend clinics within four weeks of appointment were assumed abandoned treatment. Survival curves were estimated using the Kaplan–Meier method.

Results

We identified 230 adult and 38 children refugee diagnosed with cancer during the study period. With regards to adult patients, there were 114 (49.6%) male and 116 (50.4%) female. The median age at diagnosis was 52.4, 47.3 years for male, female respectively. The five most common cancer by site among all were; breast (24.8%), colorectal (10.9%), lung (7.4%), central nervous system (CNS) (7.0%), and stomach (5.2%). 93 (40.4%) had metastatic disease at diagnosis. The overall survival probability was 37.5% at five years for the adult population. Data were extracted for 20 boys and 18 girls with childhood cancer. Their median age at diagnosis was 5.8 and 6.0 years respectively. The three most common childhood cancer were; leukemias (21.1%), lymphomas (21.1%), and CNS (13.2%). Excluding leukemia, 13 (43.3%) of childhood cancer cases had the advanced disease at diagnosis. Three year survival probality was 69.5%. The median diagnostic interval for adult and childhood cancer was 96.5 (IQR = 53–165) and 23 (IQR = 13.5–59) days respectively. Twenty-one adults and four children had treatment abandonment.

Conclusion

This study contributes to understanding the burden of cancer among Syrian refugees living in Konya, growing health issue for refugees. Larger and prospective studies will help to measure the real burden and compare the difference in cancer risk factors, care, and outcomes among the refugee and host populations.
Universal prediction of cell-cycle position using transfer learning
Authors: Zheng Shijie C. , Stein-O’Brien Genevieve , Augustin Jonathan J. , Slosberg Jared , Carosso Giovanni A. , Winer Briana , Shin Gloria , Bjornsson Hans T. , Goff Loyal A. , Hansen Kasper D.
Published: January 2022

Background

The cell cycle is a highly conserved, continuous process which controls faithful replication and division of cells. Single-cell technologies have enabled increasingly precise measurements of the cell cycle both as a biological process of interest and as a possible confounding factor. Despite its importance and conservation, there is no universally applicable approach to infer position in the cell cycle with high-resolution from single-cell RNA-seq data.

Results

Here, we present tricycle, an R/Bioconductor package, to address this challenge by leveraging key features of the biology of the cell cycle, the mathematical properties of principal component analysis of periodic functions, and the use of transfer learning. We estimate a cell-cycle embedding using a fixed reference dataset and project new data into this reference embedding, an approach that overcomes key limitations of learning a dataset-dependent embedding. Tricycle then predicts a cell-specific position in the cell cycle based on the data projection. The accuracy of tricycle compares favorably to gold-standard experimental assays, which generally require specialized measurements in specifically constructed in vitro systems. Using internal controls which are available for any dataset, we show that tricycle predictions generalize to datasets with multiple cell types, across tissues, species, and even sequencing assays.

Conclusions

Tricycle generalizes across datasets and is highly scalable and applicable to atlas-level single-cell RNA-seq data.
VirStrain: a strain identification tool for RNA viruses
Authors: Liao Herui , Cai Dehan , Sun Yanni
Published: January 2022

Viruses change constantly during replication, leading to high intra-species diversity. Although many changes are neutral or deleterious, some can confer on the virus different biological properties such as better adaptability. In addition, viral genotypes often have associated metadata, such as host residence, which can help with inferring viral transmission during pandemics. Thus, subspecies analysis can provide important insights into virus characterization. Here, we present VirStrain, a tool taking short reads as input with viral strain composition as output. We rigorously test VirStrain on multiple simulated and real virus sequencing datasets. VirStrain outperforms the state-of-the-art tools in both sensitivity and accuracy.
MOntelukast as a potential CHondroprotective treatment following Anterior cruciate ligament reconstruction (MOCHA Trial): study protocol for a double-blind, randomized, placebo-controlled clinical trial
Authors: Jacobs Cale A. , Conley Caitlin E. W. , Kraus Virginia Byers , Lansdown Drew A. , Lau Brian C. , Li Xiaojuan , Majumdar Sharmila , Spindler Kurt P. , Lemaster Nicole G. , Stone Austin V.
Published: January 2022

Background

After anterior cruciate ligament (ACL) reconstruction, patient-reported outcomes are improved 10 years post-surgery; however, cytokine concentrations remain elevated years after surgery with over 80% of those with combined ACL and meniscus injuries having posttraumatic osteoarthritis (PTOA) within 10–15 years. The purpose of this multicenter, randomized, placebo-controlled trial is to assess whether a 6-month course of oral montelukast after ACL reconstruction reduces systemic markers of inflammation and biochemical and imaging biomarkers of cartilage degradation.

Methods

We will enroll 30 individuals undergoing primary ACL reconstruction to participate in this IRB-approved multicenter clinical trial. This trial will target those at greatest risk of a more rapid PTOA onset (age range 25–50 with concomitant meniscus injury). Patients will be randomly assigned to a group instructed to take 10 mg of montelukast daily for 6 months following ACL reconstruction or placebo. Patients will be assessed prior to surgery and 1, 6, and 12 months following surgery. To determine if montelukast alters systemic inflammation following surgery, we will compare systemic concentrations of prostaglandin E2, monocyte chemoattractant protein-1, and pro-inflammatory cytokines between groups. We will also compare degradative changes on magnetic resonance imaging (MRI) collected 1 and 12 months following surgery between groups with reductions in early biomarkers of cartilage degradation assessed with urinary biomarkers of type II collagen breakdown and bony remodeling.

Discussion

There is a complex interplay between the pro-inflammatory intra-articular environment, underlying bone remodeling, and progressive cartilage degradation. PTOA affects multiple tissues and appears to be more similar to rheumatoid arthritis than osteoarthritis with respect to inflammation. There is currently no treatment to delay or prevent PTOA after ACL injury. Since there is a larger and more persistent inflammatory response after ACL reconstruction than the initial insult of injury, treatment may need to be initiated after surgery, sustained over a period of time, and target multiple mechanisms in order to successfully alter the disease process. This study will assess whether a 6-month postoperative course of oral montelukast affects multiple PTOA mechanisms. Because montelukast administration can be safely sustained for long durations and offers a low-cost treatment option, should it be proven effective in the current trial, these results can be immediately incorporated into clinical practice.

Trial registration

ClinicalTrials.govNCT04572256. Registered on October 1, 2020.
Baseline susceptibility of a wild strain of main vectors of leishmaniasis to WHO-recommended insecticides in southeastern Iran
Authors: Salim Abadi Yaser , Sanei-Dehkordi Alireza , Hakimi Parizi Maryam , Aghaei Afshar Abass , Sharifi Iraj , Gorouhi Mohammad Amin , Shirani-Bidabadi Leila , Alizadeh Ismaeil
Published: January 2022

Background

In Iran, both cutaneous leishmaniases (CL) and visceral leishmaniases (VL) are endemic, recording one of the 10 highest CL prevalence in the world. Parasites are transmitted by the bite of infectedPhlebotomussand fly females. Several sand fly species have been identified as vectors in the studied region of Kerman province. Residual spraying to control adult sand flies, is the only way to decrease the spreading of the diseases but, following control treatment against malaria vectors in endemic areas in Iran, resistance or tolerance to insecticides emerged in some sand fly species. The objective of this study was to survey insecticides susceptibility levels of 3 vector species in wild sand fly populations in different foci of the diseases in Kerman province.Ph. sergenti, andPh. papatasirespectively vectors of anthroponotic and zoonotic cutaneous leishmaniases and for the first timePh. alexandrione of the anthroponotic visceral leishmaniases vector were tested against: deltamethrin 0.05%, malathion 5%, dichloro-diphenyl-trichloroethane (DDT) 4%.

Materials and methods

In leishmaniases endemic areas species specific sand fly sites were selected in Kerman province, and specimens were collected by manual aspirators at different time intervals during the spring and summer 2019. All the susceptibility tests were performed according to the WHO tube test recommended procedure.

Results

Twenty five blood-fed female sand flies from the region's prevalent species were used in each pooled test replicates. All wild specimens died within 60 min of exposure to DDT 4%, malathion 5%, and deltamethrin 0.05%, but the mortality rate forPh. papatasiexposed to malathion and DDT was 91.6% and 66.6%, respectively.

Conclusion

According to current study results,Ph. sergentiandPh. alexandriare highly susceptible to all the evaluated insecticides in the study areas. However,Ph. papatasiwas susceptible to deltamethrin (100% mortality), possibly resistant or tolerant to malathion (91.6% mortality), and confirmed to be resistant to DDT (66.6% mortality).

Graphical Abstract
Role of the S100 protein family in rheumatoid arthritis
Authors: Wu Yuan-yuan , Li Xiao-feng , Wu Sha , Niu Xue-ni , Yin Su-qin , Huang Cheng , Li Jun
Published: January 2022

Rheumatoid arthritis is a chronic systemic autoimmune disease characterized by synovial hyperplasia, inflammatory cell infiltration, and proliferation of inflammatory tissue (angiogranuloma). The destruction of joints and surrounding tissues eventually causes joint deformities and dysfunction or even loss. The S100 protein family is one of the biggest subtribes in the calcium-binding protein family and has more than 20 members. The overexpression of most S100 proteins in rheumatoid arthritis is closely related to its pathogenesis. This paper reviews the relationship between S100 proteins and the occurrence and development of rheumatoid arthritis. It will provide insights into the development of new clinical diagnostic markers and therapeutic targets for rheumatoid arthritis.
Differences between Staphylococcus aureus nasal carriage and IgE-sensitization to Staphylococcus aureus enterotoxin on risk factors and effects in adult population
Authors: Park Han-Ki , Yoo Seok-Ju , Kim Taek Soo , Kim Byung-Keun , Jang Sekyung , Kim Sung Yeon , Lee Kwan
Published: January 2022

Background

Staphylococcus aureus (SA) nasal carriage (SA carriage) and IgE-sensitization to SA enterotoxin (SE IgE-sensitization) are known to be associated with chronic airway disease.

Objective

This study aimed to evaluate the differences in risk factors, type 2 inflammation and respiratory symptoms between SA carriage and SE IgE-sensitization.

Methods

We conducted a cross-sectional study of a community-based adult population to evaluate the environmental exposure and health impact of the Pohang Industrial Complex, Korea. Participants were examined based on self-reported questionnaires, nasal swab, and blood sampling.

Results

There were 307 participants, and the overall prevalence of SA carriage and SE IgE-sensitization was 26.1% (80/307) and 25.7% (79/307), respectively. An urban environment was significantly correlated with SA carriage, whereas age and obesity were significantly correlated with SE IgE-sensitization. SA carriage was not associated with an increase in total IgE and blood eosinophil count, whereas SE IgE-sensitization was associated with an increased total IgE and blood eosinophil count. SA carriage was significantly correlated with cough persisting for more than three weeks (OR, 3.044; 95% CI, 1.137–8.153) and sputum (OR, 2.429; 95% CI, 1.008–5.854). SE IgE-sensitization was a significant correlation with only sputum (OR, 2.452; 95% CI, 1.066–5.640). SA carriage and SE IgE-sensitization showed a synergistic effect on the prevalence of cough and sputum.

Conclusion

SA carriage was associated with the urban environment, and SE IgE-sensitization was associated with the elderly and obesity. SA carriage and SE IgE-sensitization had different correlation with type 2 inflammation and airway symptoms.
Modified oral food challenge protocol approach in the diagnosis of Food Protein-Induced Enterocolitis Syndrome
Authors: Sultafa Jessica , McKibbon Lundy , Roberts Hannah , Sarraj Jumana , Kim Harold
Published: January 2022

Background

Food Protein-Induced Enterocolitis Syndrome (FPIES) is a non-IgE mediated food allergy most commonly presenting in infants. The most common food triggers include soy, cow’s milk and grains. Symptoms may include intractable vomiting, diarrhea, lethargy, pallor, abdominal distention, hypotension and/or shock. Oral food challenges (OFCs) given at food protein dose of 0.06–0.6 g/kg in 3 equivalent doses administered over a few hours are recommended in guidelines to confirm a diagnosis.

Case presentation

The patient is a 6-month-old girl with a history of severe FPIES symptoms to egg. In our clinic, we perform OFC with 1/100 serving dose on visit 1 and then increase the dose monthly. The patient takes the tolerated dose daily at home between visits. An OFC to baked egg at 1/100 of a serving was performed and was well-tolerated on her initial visit. The patient remained on the same dose upon returning home. Within 1-week, she developed FPIES symptoms including watery diarrhea and severe emesis requiring ondansetron. She required an Emergency Department visit for one of the reactions.

Conclusions

Our patient had severe FPIES symptoms with a small amount of egg. We believe that administration of three large food challenge doses on one clinic visit, as guidelines currently suggest, does not allow adequate time for symptoms to appear. Our patient likely would have suffered a severe reaction. Also, this guidelines protocol does not allow for monitoring of more delayed or chronic FPIES. We propose a modified protocol to OFCs with cautious up-dosing to allow for safer OFCs and monitoring of chronic FPIES. We have implemented an OFC approach where only one food challenge dose (starting with 1/100 of final dose) is given at each visit. The up-titration of the dose is completed every 4-weeks with one dose only. When the serving sized dose is reached and tolerated, the food can be maintained in the diet.
Cytomegalovirus pneumonitis amid COVID-19 chaos: the hidden enemy—a case report
Authors: Aldehaim Abdulkarim Yousef , Alfaifi Abrar Mohammed , Hussain Seham Nehdal , Alrajhi Abdulaziz Mohammed
Published: January 2022

Background

The effect of coronavirus disease 2019 on the immune system is increasingly recognized. When severe, it causes immune dysregulation that may favor other infections, including Herpesviridae. Cytomegalovirus shares many innate immune pathways with severe acute respiratory syndrome coronavirus 2, which may potentiate each other. We describe a case of cytomegalovirus pneumonitis complicating the course of coronavirus disease 2019 in a patient with systemic lupus erythematosus/systemic sclerosis overlap and usual interstitial pneumonia, mimicking interstitial lung disease exacerbation. To the best of the authors’ knowledge, this is the first case to be reported worldwide in the setting of connective tissue disease-associated interstitial lung disease.

Case description

We describe the case of a 47-year-old white/Yemeni female who is known to have systemic lupus erythematosus/scleroderma overlap and usual interstitial pneumonia who was initially admitted with severe coronavirus disease 2019 pneumonia mandating intensive care. After initial improvement, it was later complicated with cytomegalovirus pneumonitis, mimicking interstitial lung disease exacerbation. The case was successfully treated with ganciclovir.

Conclusion

Intriguingly, severe acute respiratory syndrome coronavirus 2 and cytomegalovirus may potentiate each other, since they share some innate immune pathways. Subjects with severe coronavirus disease 2019 and underlying connective tissue diseases and those who are immunosuppressed carry higher risk compared with other cohorts, which may mandate active surveillance for cytomegalovirus coinfection or reactivation. Among various immunosuppressive therapies that has been tried for cytokine storm, use of anti-interleukin-6 inhibitors in the aforementioned population may carry more harm than previously thought, which may suggest that is reasonable to omit its use in treating this group with coronavirus disease 2019. This case underlines an underrecognized and underreported cause of morbidity and mortality during the course of severe coronavirus disease 2019 and will help to alert clinicians of its occurrence.
Quality of care indicator performance was minimally changed in 2020 despite the COVID-19 pandemic
Authors: Konson Alexander , Kuniavsky Michael , Bronshtein Olga , Goldschmidt Nethanel , Hanhart Shuli , Mahalla Hannah , Peri Shir , Dollberg Shaul , Niv Yaron
Published: January 2022

Background

In 2020, the COVID-19 pandemic affected healthcare systems throughout the world, including the management of patients and compliance rates of quality indicators.

Objective

To measure the impact in Israel of the COVID-19 pandemic on the indicator-relevant caseload and compliance rates of the quality indicators reported by medical services providers within the Israeli National Program for Quality Indicators (NPQI).

Methods

Data was collected from the reports made to the NPQI by participating hospitals and medical service providers. The indicator results for the number of cases and compliance rates for 2019 were compared to those from 2020. We assessed and compared the results of the quality indicators in general hospitals, geriatric hospitals and departments, psychiatric hospitals and departments, emergency medical services (EMS), and Mother and Baby health centers.

Results

We found a decrease in measurable cases in 2020 relative to 2019, especially in geriatric hospitals. In most indicators, compliance rates rose in 2020. Few indicators had lower compliance rates associated with COVID-19 pandemic regulations.

Conclusions and policy implications

Routine medical activity decreased in Israel in 2020 in comparison to 2019, as reflected by a decrease in cases, but compliance rates were better in most indicators. The results of our study imply that the functioning of healthcare quality measurement programs should not be interrupted during a pandemic. This not only allows measuring of the healthcare system's performance during a crisis, but also may assist in maintaining a high level of healthcare quality.
Experiences of weight stigmatization in the Israeli healthcare system among overweight and obese individuals
Authors: Sagi-Dain Lena , Echar Moran , Paska-Davis Naama
Published: January 2022

Introduction

Weight stigmatization, a common phenomenon in the healthcare system, exerts numerous adverse consequences on patients' wellbeing. The objective of this study was to estimate the extent and characteristics of weight stigmatization in Israel, based on the reports of overweight and obese individuals.

Methods

This study was performed by distribution of a cross-sectional open anonymous survey in social media platforms, targeting respondents with body mass index over 25 kg/m2. The questionnaire consisted of Likert-scale based as well as open-ended questions, evaluating the experience during past medical appointments. Our primary outcome was the prevalence of disrespectful treatment. Subgroup analysis was performed by various demographic characteristics.

Results

Of the 1697 respondents, 59.0% reported frequent experiences of disrespectful approach, and 48.6% noted receiving suboptimal treatment related to excess weight. Insulting, insensitive and judgmental comments were noted by 58%, stemming from diverse healthcare disciplines, while 29.3% noted office equipment not suitable for overweight people. Avoidance of a needed medical appointment was reported by 40.5%, significantly associated with past adverse experiences of weight stigmatization in the healthcare system. The respondents offered numerous suggestions to improve the existing situation, including education of the medical personnel, thorough research of obesity, and establishment of specific guidelines for approach to patients with excess weight.

Conclusion

Weight stigmatization is prevalent in Israeli healthcare system; thus, decreasing the rates of this phenomenon should be an important national goal. Formal education about the wide prevalence and adverse effects of weight stigmatization should be practiced by academic institutions, professional organizations, and regulatory bodies. Straightforward policies with continuing supervision should be endorsed by the healthcare system to prevent weight-based discrimination. Finally, appropriate-size equipment for obese patients should become one of the requirements for accreditation of medical centers and facilities.
Snapshot compressive spectral - depth imaging based on light field
Authors: Ding Xiaoming , Yan QiangQiang , Hu Liang , Zhou Shubo , Wei Ruyi , Wang Xiaocheng , Li Yupeng
Published: January 2022

This paper proposes a snapshot Compressed Light Field Imaging Spectrometer based on compressed sensing and light field concept, which can acquire the two-dimensional spatial distribution, depth estimation and spectral intensity of input scenes simultaneously. The primary structure of the system contains fore optics, coded aperture, dispersion element and light field sensor. The detected data can record the coded mixture spatial-spectral information of the input scene with direction information of light rays. The datacube containing depth estimation can be recovered with the compressed sensing and digital refocus framework. We establish the mathematical model of the system and conduct simulations for verification. The reconstruction strategy is demonstrated for the simulation data.
From the Fan-KKM principle to extended real-valued equilibria and to variational-hemivariational inequalities with application to nonmonotone contact problems
Authors: Gwinner Joachim
Published: January 2022

This paper starts off by the celebrated Knaster–Kuratowski–Mazurkiewicz principle in the formulation by Ky Fan. We provide a novel variant of this principle and build an existence theory for extended real-valued equilibrium problems with general, then monotone and pseudomonotone bifunctions. We develop our existence theory first in general topological vector spaces, then in reflexive Banach spaces, where we investigate the issue of coerciveness for existence on unbounded sets. Thereafter we use the Clarke generalized differential calculus for locally Lipschitz functions and derive existence results for nonlinear variational-hemivariational inequalities and hemivariational quasivariational inequalities. As application, we treat a unilateral contact problem in solid mechanics with nonmonotone friction.
Intellectual capital factors at work in Dominican firms: understanding their influence
Authors: Gómez-Valenzuela Víctor
Published: January 2022

From an empirical-based perspective, this paper explores the influence of intellectual capital factors on the performance of firms in the Dominican Republic. A Likert scale from one to seven was used to capture firms’ sensitivity to human, structural and relational capital factors. An exploratory factor analysis was carried out using the method of principal components with VARIMAX rotation. The final factorial scores were standardized to execute the regression analysis. Structural capital factors appear to be the dominant intellectual capital components within the Dominican context. Human capital factors play a vital role in performance in manufacturing and in-services firms, and relational capital factors are significant in determining their performance. This research contributes to the regional literature on intellectual capital studies in Latin America and the Caribbean. It puts forward some specific points related to the role of intellectual capital factors in explaining firms’ performance in small open economies such as that of the Dominican Republic.