bluuebunny/crossref_metadata_2025 huggingface dataset:
Modifiable prognostic factors of high costs related to healthcare utilization among older people seeking primary care due to back pain: an identification and replication study
Authors: Killingmo Rikke Munk , Chiarotto Alessandro , van der Windt Danielle A. , Storheim Kjersti , Bierma-Zeinstra Sita M. A. , Småstuen Milada C. , Zolic-Karlsson Zinajda , Vigdal Ørjan N. , Koes Bart W. , Grotle Margreth
Published: June 2022

Background

Back pain is an extensive burden to our healthcare system, yet few studies have explored modifiable prognostic factors associated with high costs related to healthcare utilization, especially among older back pain patients. The aims of this study were to identify modifiable prognostic factors for high costs related to healthcare utilization among older people seeking primary care with a new episode of back pain; and to replicate the identified associations in a similar cohort, in a different country.

Methods

Data from two cohort studies within the BACE consortium were used, including 452 and 675 people aged ≥55 years seeking primary care with a new episode of back pain. High costs were defined as costs in the top 25th percentile. Healthcare utilization was self-reported, aggregated for one-year of follow-up and included: primary care consultations, medications, examinations, hospitalization, rehabilitation stay and operations. Costs were estimated based on unit costs collected from national pricelists. Nine potential modifiable prognostic factors were selected based on previous literature. Univariable and multivariable binary logistic regression models were used to identify and replicate associations (crude and adjusted for selected covariates) between each modifiable prognostic factor and high costs related to healthcare utilization.

Results

Four modifiable prognostic factors associated with high costs related to healthcare utilization were identified and replicated: a higher degree of pain severity, disability, depression, and a lower degree of physical health-related quality of life. Kinesiophobia and recovery expectations showed no prognostic value. There were inconsistent results across the two cohorts with regards to comorbidity, radiating pain below the knee and mental health-related quality of life.

Conclusion

The factors identified in this study may be future targets for intervention with the potential to reduce high costs related to healthcare utilization among older back pain patients.

Trial registration

ClinicalTrials.govNCT04261309, 07 February 2020. Retrospectively registered.
Substance P concentrations in the blood plasma and serum of adult cattle and calves during different painful procedures and conditions – a systematic review
Authors: Tschoner Theresa , Feist Melanie
Published: June 2022

Background

Pain in cattle is a major welfare problem, as cattle mask their pain. Subjective and objective parameters to assess pain in cattle have been described. Among the objective parameters to evaluate pain in cattle is substance P (SP). SP is a neurotransmitter, which is involved in the processing of noxious information to the brain; it seems to be a more objective indicator for nociception than cortisol, which has long been used as a biomarker for pain and stress in cattle. The objective of this systematic review was to assess the existing literature about SP during painful procedures, conditions, and diseases in cattle in form of a systematic review.

Results

Following the PRISMA statement, 36 out of 236 studies were included in this systematic review. Study design, grouping, age and weight of animals, processing of blood samples for the assessment of SP, and results were heterogenous. The largest number of studies originated from the United States of America and Canada and were published in 2018. A higher number of studies were done on calves (69.4%,n = 25) compared with adult cattle (30.6%,n = 11). Most studies were done to assess SP concentrations after administration of analgesics prior to husbandry procedures in calves.

Conclusions

There is a manageable number of studies assessing SP concentrations during painful procedures, conditions, and diseases in cattle. SP seems to be a suitable biomarker for nociception in cattle, but results of research work are heterogenous, and SP concentrations of calves and adult cattle differ throughout studies. Basic research work is missing and is needed to assess factors others than nociception which might influence the SP concentrations in the blood plasma.
Ellagic acid Alleviates hepatic ischemia–reperfusion injury in C57 mice via the Caspase-1-GSDMD pathway
Authors: Wang Hao , Miao Fujun , Ning Delu , Shan Chunlan
Published: June 2022

Background

Ellagic acid (EA) has improving function against oxidative damage and inflammatory reaction in many disorders. Hepatic ischemia–reperfusion injury (IRI) is a common pathophysiological phenomenon in the veterinary clinic. In the present study, the protective effects of EA pretreatment against hepatic IRI-induced injury and the underlying mechanisms were investigated.

Results

We found that pyroptosis is involved in hepatic IRI, which is manifested in increasing the expression of pyroptosis-related genes and promoting the expression of active caspase-1, thereby cleaving GSDMD-N to cause pyroptosis, and caspase-1−/− mice were used to verify this conclusion. In addition, we found that EA protects against hepatic IRI by inhibiting pyroptosis, including reducing the activity of caspase-1 and its expression in the liver, inhibiting the lysis of GSDMD-N, and reducing the levels of IL-18 and IL-1β.

Conclusions

The present results have demonstrated that prophylactic administration of EA ameliorated hepatic IRI by inhibiting pyroptosis induced in hepatic ischemia–reperfusion in vivo through the caspase-1-GSDMD axis, providing a potential therapeutic option prevent hepatic IRI in pets.
Serological investigation of Gyrovirus homsa1 infections in chickens in China
Authors: Zhang Shicheng , Yuan Shiyu , Yan Tianxing , Li Gen , Hao Xiaojing , Zhou Defang , Li Ruiqi , Li Yubao , Cheng Ziqiang
Published: June 2022

Background

Gyrovirus homsa1 (GyH1) (also known as Gyrovirus 3, GyV3) is a non-enveloped, small, single-stranded DNA virus, which was first identified in children with acute diarrhea, and was subsequently detected in marketed chickens, broilers with transmissible viral proventriculitis (TVP), and mammals. GyH1 is a pathogenic virus in chickens, causing aplastic anemia, immunosuppression, and multisystem damage. However, the seroepidemiology of GyH1 infection in chickens remains unclear. Here, we investigated the seroprevalence of GyH1 in chickens by ELISA to reveal the endemic status of GyH1 in China.

Results

An indirect ELISA with high sensitivity and specificity was developed for investigation of seroepidemiology of GyH1 in chickens in China. The seropositive rate of GyH1 ranged from 0.6% to 7.7% in thirteen provinces, and ranged from 4.1% to 8.1% in eight species chickens. The seropositive rate of GyH1 in broiler breeders was significantly higher than that of in layers. There was a negative correlation between seropositive rate and age of chickens. The highest and lowest seropositive rate were present in chickens at 30–60 days and over 180 days, respectively.

Conclusions

The seroepidemiological investigation results demonstrated that natural GyH1 infection is widespread in chickens in China. Different species showed different susceptibility for GyH1. Aged chickens showed obvious age-resistance to GyH1. GyH1 has shown a high risk to the poultry industry and should be highly concerned.
Molecular epidemiological study of germline APC variant associated with hereditary gastrointestinal polyposis in dogs: current frequency in Jack Russell Terriers in Japan and breed distribution
Authors: Yoshizaki Kyoko , Hirata Akihiro , Matsushita Hiroyuki , Sakaguchi Masahiro , Yoneji Wakana , Owaki Keishi , Sakai Hiroki
Published: June 2022

Background

Cases of gastrointestinal (GI) neoplastic polyps in Jack Russell Terriers (JRTs) have increased in Japan since the late 2000s. We recently demonstrated that JRTs with GI polyps heterozygously harbor an identical germline variant in the adenomatous polyposis coli (APC) gene, c.[462_463delinsTT]; therefore, this is an autosomal dominant hereditary disease. We conducted a molecular epidemiological study to explore the current frequency of the APC variant in JRTs in Japan and the breed distribution of this disease.

Results

Peripheral blood samples from 792 JRTs were collected at 93 veterinary hospitals in Japan in 2020. Using an established polymerase chain reaction-restriction fragment length polymorphism assay, the germline APC variant was detected in 15 JRTs, with an overall frequency of 1.89%. The frequency was not significantly different for sex, age, and coat type criteria. Notably, the variant carriers had a current or previous history of GI neoplastic polyps, providing further evidence of the association of the germline APC variant with GI polyposis. Pedigree analysis of carrier dogs revealed that the germline APC variant was no longer confined to a few specific families but was widely spread among JRTs in Japan. Furthermore, some ancestors of the carriers were from Australia or New Zealand, suggesting the possible presence of carriers in countries other than Japan. Next, we retrospectively investigated the germline APC variant status of dogs with GI epithelial tumors using genomic DNA samples extracted from archived pathological specimens (28 purebred dogs of 14 breeds and four mixed-breed dog), as well as those stored in a canine genome bank (38 dogs of 18 breeds and a mixed-breed dogs). In total, 66 purebred dogs of 25 breeds, including another four JRTs, and five mixed-breed dogs were examined. While three variant carriers were found in JRTs, the germline APC variant was not detected in any of the other breeds.

Conclusion

The current frequency of the germline APC variant was approximately 2% in JRTs in Japan and the frequency remained roughly flat during the last 15 years. In addition, hereditary GI polyposis associated with the variant was virtually specific to JRTs.
First case report of complete paternal isodisomy of chromosome 10 harbouring a novel variant in COL17A1 that causes junctional epidermolysis bullosa intermediate
Authors: Wang Yao , Yu Dong , Wei Wei , Zheng Hao , Liu Ming-Hua , Ma Long , Qin Li-Na , Wang Neng-Zhuang , Li Jia-Xi , Wang Jin-Jiang , Bi Xin-Ling , Yan Hong-Li
Published: June 2022

Background

Uniparental disomy (UPD) is a condition in which both chromosomes are inherited from the same parent, except for imprinting disorders. Uniparental isodisomy (UPiD) may result in a homozygous variant contributing to an autosomal recessive disorder in the offspring of a heterozygous carrier. Junctional epidermolysis bullosa intermediate (JEB intermediate) is an autosomal recessive inherited disease that is associated with a series of gene variants, including those of COL17A1.

Case presentation

We report the first case of complete paternal UPiD of chromosome 10 harbouring a novel homozygous variant in COL17A1: c.1880(exon23)delG (p.G627Afs*56). This variant led to the clinical phenotype of junctional epidermolysis bullosa intermediate in a 5-year-old child. Trio-whole exome sequencing (Trio-WES) and in silico data analysis were used for variant identification, Sanger sequencing was performed for variant validation, and pathological examination was performed as the gold standard for phenotype confirmation.

Conclusions

We recommend the use of WES as a first-tier test for the diagnosis of epidermolysis bullosa, especially for paediatric patients. Moreover, UPD events should be detected and analysed routinely through WES data in the future.
Long-term clinical course and outcomes in patients with lymphangioleiomyomatosis
Authors: Yoon Hee-Young , Kim Ho Jeong , Song Jin Woo
Published: June 2022

Background

Lymphangioleiomyomatosis (LAM) is a rare multisystemic disorder with various clinical manifestations. Despite the recognition of several prognostic factors, the long-term clinical course and prognosis of patients with LAM in the era of sirolimus therapy are not established.

Methods

The clinical data of 104 patients with LAM were retrospectively analyzed. Death or lung transplantation was defined as the primary outcome. Disease progression (DP) was defined as a 10% absolute decline in forced expiratory volume in one second (FEV1).

Results

The mean age of all patients was 40.3 years. Over a median follow-up period of 7.1 years, of all patients, 6.7% died and 1.9% underwent lung transplantation, while of 92 patients with serial lung function data, 35.9% experienced DP. The 5-year and 10-year overall survival rates were 93.0% and 90.9%, respectively. The multivariable Cox analysis revealed that older age (hazard ratio [HR]: 1.136, P = 0.025), lower FEV1 (HR: 0.956, P = 0.026) or diffusing capacity for carbon monoxide (HR: 0.914, P = 0.003), and shorter distance during the 6-min walk test (HR: 0.993, P = 0.020) were independent prognostic factors for mortality. A propensity score-matched comparative analysis performed between patients who received sirolimus therapy and those who did not, found no differences in survival, DP, complications, and lung function decline rate.

Conclusions

Over a follow-up period of approximately 7 years, one-tenth of all patients experienced death, while one-third experienced DP. Older age, lower lung function, and reduced exercise capacity were associated with a poor prognosis in patients with LAM.
Increased susceptibility to organic dust exposure-induced inflammatory lung disease with enhanced rheumatoid arthritis-associated autoantigen expression in HLA-DR4 transgenic mice
Authors: Poole Jill A. , Mikuls Ted R. , Thiele Geoffrey M. , Gaurav Rohit , Nelson Amy J. , Duryee Michael J. , Mitra Ananya , Hunter Carlos , Wyatt Todd A. , England Bryant R. , Ascherman Dana P.
Published: June 2022

Immunogenetic as well as environmental and occupational exposures have been linked to the development of rheumatoid arthritis (RA), RA-associated lung disease, and other primary lung disorders. Importantly, various inhalants can trigger post-translational protein modifications, resulting in lung autoantigen expression capable of stimulating pro-inflammatory and/or pro-fibrotic immune responses. To further elucidate gene-environment interactions contributing to pathologic lung inflammation, we exploited an established model of organic dust extract (ODE) exposure with and without collagen-induced arthritis (CIA) in C57BL/6 wild type (WT) versus HLA-DR4 transgenic mice. ODE-induced airway infiltration driven by neutrophils was significantly increased in DR4 versus WT mice, with corresponding increases in bronchoalveolar lavage fluid (BALF) levels of TNF-⍺, IL-6, and IL-33. Lung histopathology demonstrated increased number of ectopic lymphoid aggregates comprised of T and B cells following ODE exposure in DR4 mice. ODE also induced citrullination, malondialdehyde acetaldehyde (MAA) modification, and vimentin expression that co-localized with MAA and was enhanced in DR4 mice. Serum and BALF anti-MAA antibodies were strikingly increased in ODE-treated DR4 mice. Coupling ODE exposure with Type II collagen immunization (CIA) resulted in similarly augmented pro-inflammatory lung profiles in DR4 mice (relative to WT mice) that was accompanied by a profound increase in infiltrating lung CD4+and CD8+T cells as well as CD19+CD11b+autoimmune B cells. Neither modeling strategy induced significant arthritis. These findings support a model in which environmental insults trigger enhanced post-translational protein modification and lung inflammation sharing immunopathological features with RA-associated lung disease in the selected immunogenetic background of HLA-DR4 mice.
Normal fasting triglyceride levels and incident type 2 diabetes in the general population
Authors: Szili-Torok Tamas , Bakker Stephan J. L. , Tietge Uwe J. F.
Published: June 2022

Background

Type 2 diabetes is increasing worldwide. Traditionally, only hypertriglyceridemia is considered a risk factor. We investigated whether also normal triglycerides prospectively associate with incident type 2 diabetes in healthy subjects.

Methods

Incident type 2 diabetes was determined in healthy individuals with normal triglyceride levels from a prospective longitudinal cohort study (PREVEND, n = 2085, 11.4-year median follow-up).

Results

Type 2 diabetes incidence was 3.8%. In linear regression analysis baseline insulin, HOMA-IR, total cholesterol, HDL cholesterol, eGFR, systolic blood pressure (all p < 0.001), glucose, age and creatinine (all p < 0.01) independently associated with triglycerides within the normal range, comparable to what would be expected from associations with increased triglycerides. In Kaplan-Meier analysis sex-stratified tertiles of normal triglycerides prospectively associated with de novo type 2 diabetes (p < 0.001). Cox regression confirmed a significant prospective association independent of HOMA-IR [HR (95% CI), 1.39 (1.12, 1.74), p = 0.002] and several other recognized risk factors.

Conclusions

Even in healthy subjects without metabolic syndrome increasing triglyceride levels within the normal range confer a continuous increase in type 2 diabetes incidence. These data indicate that virtually everyone could potentially benefit from triglyceride lowering, further encouraging implementation of lifestyle changes in the general population.
PhoP- and GlnR-mediated regulation of metK transcription and its impact upon S-adenosyl-methionine biosynthesis in Saccharopolyspora erythraea
Authors: Pei Jin-Feng , Li Yu-Xin , Tang Hao , Wei Wenping , Ye Bang-Ce
Published: June 2022

Background

Erythromycin A (Er A) has a broad antibacterial effect and is a source of erythromycin derivatives. Methylation of erythromycin C (Er C), catalyzed by S-adenosyl-methionine (SAM)-dependent O-methyltransferase EryG, is the key final step in Er A biosynthesis. Er A biosynthesis, including EryG production, is regulated by the phosphate response factor PhoP and the nitrogen response factor GlnR. However, the regulatory effect of these proteins upon S-adenosyl-methionine synthetase (MetK) production is unknown.

Results

In this study, we used bioinformatics approaches to identify metK (SACE_3900), which codes for S-adenosyl-methionine synthetase (MetK). Electrophoretic mobility shift assays (EMSAs) revealed that PhoP and GlnR directly interact with the promoter of metK, and quantitative PCR (RT-qPCR) confirmed that each protein positively regulated metK transcription. Moreover, intracellular SAM was increased upon overexpression of either phoP or glnR under phosphate or nitrogen limited conditions, respectively. Finally, both the production of Er A and the transformation ratio from Er C to Er A increased upon phoP overexpression, but surprisingly, not upon glnR overexpression.

Conclusions

Manipulating the phosphate and nitrogen response factors, PhoP and GlnR provides a novel strategy for increasing the yield of SAM and the production of Er A in Saccharopolyspora erythraea .
Towards synthetic PETtrophy: Engineering Pseudomonas putida for concurrent polyethylene terephthalate (PET) monomer metabolism and PET hydrolase expression
Authors: Brandenberg Oliver F. , Schubert Olga T. , Kruglyak Leonid
Published: June 2022

Background

Biocatalysis offers a promising path for plastic waste management and valorization, especially for hydrolysable plastics such as polyethylene terephthalate (PET). Microbial whole-cell biocatalysts for simultaneous PET degradation and growth on PET monomers would offer a one-step solution toward PET recycling or upcycling. We set out to engineer the industry-proven bacterium Pseudomonas putida for (i) metabolism of PET monomers as sole carbon sources, and (ii) efficient extracellular expression of PET hydrolases. We pursued this approach for both PET and the related polyester polybutylene adipate co-terephthalate (PBAT), aiming to learn about the determinants and potential applications of bacterial polyester-degrading biocatalysts.

Results

P. putida was engineered to metabolize the PET and PBAT monomer terephthalic acid (TA) through genomic integration of four tphII operon genes from Comamonas sp. E6. Efficient cellular TA uptake was enabled by a point mutation in the native P. putida membrane transporter MhpT. Metabolism of the PET and PBAT monomers ethylene glycol and 1,4-butanediol was achieved through adaptive laboratory evolution. We then used fast design-build-test-learn cycles to engineer extracellular PET hydrolase expression, including tests of (i) the three PET hydrolases LCC, HiC, and IsPETase; (ii) genomic versus plasmid-based expression, using expression plasmids with high, medium, and low cellular copy number; (iii) three different promoter systems; (iv) three membrane anchor proteins for PET hydrolase cell surface display; and (v) a 30-mer signal peptide library for PET hydrolase secretion. PET hydrolase surface display and secretion was successfully engineered but often resulted in host cell fitness costs, which could be mitigated by promoter choice and altering construct copy number. Plastic biodegradation assays with the best PET hydrolase expression constructs genomically integrated into our monomer-metabolizing P. putida strains resulted in various degrees of plastic depolymerization, although self-sustaining bacterial growth remained elusive.

Conclusion

Our results show that balancing extracellular PET hydrolase expression with cellular fitness under nutrient-limiting conditions is a challenge. The precise knowledge of such bottlenecks, together with the vast array of PET hydrolase expression tools generated and tested here, may serve as a baseline for future efforts to engineer P. putida or other bacterial hosts towards becoming efficient whole-cell polyester-degrading biocatalysts.
Oncogenic functions and clinical significances of DCLK1 isoforms in colorectal cancer: a systematic review and meta-analysis
Authors: Kalantari Elham , Razmi Mahdieh , Tajik Fatemeh , Asadi-Lari Mohsen , Ghods Roya , Madjd Zahra
Published: June 2022

Background

The oncogenic role of doublecortin-like kinase 1 (DCLK1) as a putative cancer stem cell (CSC) marker has been clarified in colorectal cancer (CRC). Isoform-specific functions of DCLK1 have shed new light on different functions of DCLK1 short (DCLK1-S) and DCLK1 long (DCLK1-L) isoforms in tumor initiation, growth, and metastasis. Therefore, the current systematic review and meta-analysis aimed to review the available in vitro, in vivo, and clinical evidence on the oncogenic roles and clinical significance of DCLK1 isoforms in colorectal cancer.

Methods

The literature databases of PubMed, Scopus, ISI Web of Science, and Embase were searched to identify eligible articles. The description characteristics of in vitro and pre-clinical studies were extracted from identified reports. In addition, hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were recorded to determine the relationships between DCLK1-L and DCLK1-S expression and prognostic outcomes in patients with CRC.

Results

Both in vitro and in vivo evidence have emphasized the potential oncogenic functions of DCLK1 in tumor initiation, self-renewal ability, tumor invasion, epithelial-mesenchymal transition (EMT), and metastasis. However, the anti-DCLK1 antibodies generally utilized in these studies could detect sequence homology epitopes of both isoforms. Recent limited isoform-specific evidence has strongly supported the significant positive expression and rather oncogenic efficacy of DCLK1-S in tumorigenesis, EMT, and invasion compared with DCLK1-L in human CRC cell lines. Our meta-analysis findings of limited clinical studies indicated that only overexpression of DCLK1-S is associated with worse overall survival (OS) (HR = 7.930, 95% CI 2.252–27.924, p = 0.001). Increased expression of both DCLK1-S (HR = 1.610, 95% CI 1.020–2.541, p = 0.041) and DCLK1-L (HR = 5.890, 95% CI 1.219–28.453, p = 0.027) isoforms was closely associated with worse DSS/CSS in CRC patients. Furthermore, the high expression of DCLK1-S was found to be associated with poor DFS/RFS/PFS (HR = 1.913, 95% CI 1.230–2.973, p = 0.004).

Conclusions

The current findings strongly supported that the DCLK1-S isoform may play a crucial role in the invasion, aggressive tumor behavior, and worsened survival outcomes of CRC patients. However, further critical investigations related to the potential preclinical and clinical utilities of DCLK1-S as a specific CRC-CSC marker are warranted.
Minimum variance beamforming combined with covariance matrix-based adaptive weighting for medical ultrasound imaging
Authors: Wang Yuanguo , Wang Yadan , Liu Mingzhou , Lan Zhengfeng , Zheng Chichao , Peng Hu
Published: June 2022

Background

The minimum variance (MV) beamformer can significantly improve the image resolution in ultrasound imaging, but it has limited performance in noise reduction. We recently proposed the covariance matrix-based statistical beamforming (CMSB) for medical ultrasound imaging to reduce sidelobes and incoherent clutter.

Methods

In this paper, we aim to improve the imaging performance of the MV beamformer by introducing a new pixel-based adaptive weighting approach based on CMSB, which is named as covariance matrix-based adaptive weighting (CMSAW). The proposed CMSAW estimates the mean-to-standard-deviation ratio (MSR) of a modified covariance matrix reconstructed by adaptive spatial smoothing, rotary averaging, and diagonal reducing. Moreover, adaptive diagonal reducing based on the aperture coherence is introduced in CMSAW to enhance the performance in speckle preservation.

Results

The proposed CMSAW-weighted MV (CMSAW-MV) was validated through simulation, phantom experiments, and in vivo studies. The phantom experimental results show that CMSAW-MV obtains resolution improvement of 21.3% and simultaneously achieves average improvements of 96.4% and 71.8% in average contrast and generalized contrast-to-noise ratio (gCNR) for anechoic cyst, respectively, compared with MV. in vivo studies indicate that CMSAW-MV improves the noise reduction performance of MV beamformer.

Conclusion

Simulation, experimental, and in vivo results all show that CMSAW-MV can improve resolution and suppress sidelobes and incoherent clutter and noise. These results demonstrate the effectiveness of CMSAW in improving the imaging performance of MV beamformer. Moreover, the proposed CMSAW with a computational complexity of $$O(N^2)$$

O
(

N
2

)

has the potential to be implemented in real time using the graphics processing unit.
Barriers to COVID-19 vaccination among older adults in Mexico City
Authors: Gaitán-Rossi Pablo , Mendez-Rosenzweig Miranda , García-Alberto Erika , Vilar-Compte Mireya
Published: June 2022

Vaccines are effective to reduce COVID-19 related outcomes, but universal vaccination campaigns can reveal within-country access inequities. Mexico City has had high rates of COVID-19 related morbidity and mortality and a population survey warned that vaccine acceptance was lowest in older adults. Since February 2021, Mexico started a universal and free vaccination campaign prioritizing older adults. By April 17, every older adult in Mexico City had been eligible to receive the first dose. A week later, we conducted a telephone survey representative of older adults residing in Mexico City (n = 503). We asked if they received their first dose and, if they haven’t, we followed-up with an open question to register their reasons. In addition to sociodemographic characteristics and food insecurity, we also inquired about vaccine hesitancy, health concerns related to COVID-19, self-rated health, comorbidities, frailty, and depression. The objective of the study was to identify the main barriers to receive the first dose of the vaccine. We estimated descriptive statistics and logistic regression models. Results show that 7.6% of older adults in Mexico City did not receive their first dose. Barriers for not receiving it were vaccine hesitancy (60.4%), not having COVID-19 health concerns (46.4%), poor self-rated health (46.7%), a previous diagnosis of depression (35.7%), low socioeconomic status (65.4%), and household food insecurity (59.8%). Responses to the open question clustered in four themes: misinformation about the process (30%), distrust of the vaccine (24%), personal health problems (24%), and difficulties to get an appointment (22%). Logistic regression models adjusted for vaccine hesitancy and revealed two distinct reasons for not having their first dose: 1) vaccine hesitancy and misinformation on COVID-19, and 2) household food insecurity. Reaching these two groups requires active and differentiated public-health measures; the first with additional information from trusted sources, and the second by facilitating vaccination in neighborhoods with high levels of food insecurity and informal labor, where missing a day’s work is a strong disincentive. Vaccination campaigns need an equity lens to reach universal coverage; ensuring full access demands thorough and carefully tailored new interventions.
Pleural mesothelioma risk by industry and occupation: results from the Multicentre Italian Study on the Etiology of Mesothelioma (MISEM)
Authors: Migliore Enrica , Consonni Dario , Peters Susan , Vermeulen Roel C. H. , Kromhout Hans , Baldassarre Antonio , Cavone Domenica , Chellini Elisabetta , Magnani Corrado , Mensi Carolina , Merler Enzo , Musti Marina , Marinaccio Alessandro , Mirabelli Dario
Published: June 2022

Background

The Italian mesothelioma registry (ReNaM) estimates mesothelioma incidence and addresses its etiology by assessing cases’ exposures but cannot provide relative risk estimates.

Objectives

i) To estimate pleural mesothelioma relative risk by industry and occupation and by ReNaM categories of asbestos exposure; and ii) to provide quantitative estimates of the exposure–response relationship.

Methods

A population-based mesothelioma case–control study was conducted in 2012–2014 in five Italian regions. Cases and age and gender frequency-matched controls were interviewed using a standard ReNaM questionnaire. Experts coded work histories according to international standard classifications of industries/occupations and assigned asbestos exposure according to ReNaM categories. Job codes were further linked to SYN-JEM, a quantitative job-exposure matrix. Cumulative exposure (CE, f/mL-years) was computed by summing individual exposures over lifetime work history. Unconditional logistic regression analyses adjusted by gender, centre and age were fitted to calculate odds ratios (OR) and 95% confidence intervals (CI).

Results

Among men we observed increased risks of mesothelioma in many industries and associated occupations, including: asbestos-cement (OR = 3.43), manufacture of railroad equipment (OR = 8.07), shipbuilding and repairing (OR = 2.34), iron and steel mills (OR = 2.15), and construction (OR = 1.94). ORs by ReNaM exposure categories were as follows: definite/probable occupational exposure (OR = 15.8, men; OR = 8.80, women), possible occupational (OR = 2.82, men; OR = 3.70, women), sharing home with an exposed worker (OR = 2.55, men; OR = 10.3, women), residential (OR = 2.14, men; OR = 3.24, women). Based on SYN-JEM, mesothelioma risk increased by almost 30% per f/mL-year (OR = 1.28, CI 1.16–1.42).

Conclusions

Out study involved five regions with historically different types and levels of industrial development, encompassing one third of the Italian population and half of Italian mesothelioma cases. As expected, we found increased pleural mesothelioma risk in the asbestos industry and in trades with large consumption of asbestos materials. Clear associations were found using both qualitative (ReNaM classifications) and quantitative estimates (using SYN-JEM) of past asbestos exposure, with clear evidence of an exposure–response relationship.
Deviations from typical paths: a novel approach to working with GPS data in the behavioral sciences
Authors: Nielsen Karen E. , Mejía Shannon T. , Gonzalez Richard
Published: June 2022

Background

Behavioral science researchers are increasingly collecting detailed location data such as second-by-second GPS tracking on participants due to increased ease and affordability. While intraindividual variability has been discussed in the travel literature for decades, traditional methods designed for studying individual differences in central tendencies limit the extent to which novel questions about variability in lived experiences can be answered. Thus, new methods of quantifying behavior that focus on intraindividual variability are needed to address the context in which the behavior occurs and the location tracking data from which behavior is derived.

Methods

We propose deviations from typical paths as a data processing technique to separate individual-level typical travel behavior from a location tracking data set in order to highlight atypical travel behavior as an outcome measure.

Results

A simulated data example shows how the method works to produce deviation measures from a location dataset. Analysis of these deviations offers additional insights compared to traditional measures of maximum daily distance from home.

Conclusions

This process can be integrated into larger research questions to explore predictors of atypical behavior and potential mechanisms of behavior change.
Recent advances in pain management based on nanoparticle technologies
Authors: Babaie Soraya , Taghvimi Arezou , Hong Joo-Hyun , Hamishehkar Hamed , An Seongpil , Kim Ki Hyun
Published: June 2022

Background

Pain is a vital sense that indicates the risk of injury at a particular body part. Successful control of pain is the principal aspect in medical treatment. In recent years, the advances of nanotechnology in pain management have been remarkable. In this review, we focus on literature and published data that reveal various applications of nanotechnology in acute and chronic pain management.

Methods

The presented content is based on information collected through pain management publications (227 articles up to April 2021) provided by Web of Science, PubMed, Scopus and Google Scholar services.

Results

A comprehensive study of the articles revealed that nanotechnology-based drug delivery has provided acceptable results in pain control, limiting the side effects and increasing the efficacy of analgesic drugs. Besides the ability of nanotechnology to deliver drugs, sophisticated nanosystems have been designed to enhance imaging and diagnostics, which help in rapid diagnosis of diseases and have a significant impact on controlling pain. Furthermore, with the development of various tools, nanotechnology can accurately measure pain and use these measurements to display the efficiency of different interventions.

Conclusions

Nanotechnology has started a new era in the pain management and many promising results have been achieved in this regard. Nevertheless, there is still no substantial and adequate act of nanotechnology in this field. Therefore, efforts should be directed to broad investigations.

Graphical Abstract
Cell membrane-camouflaged inorganic nanoparticles for cancer therapy
Authors: Song Wanli , Jia Pengfei , Zhang Ting , Dou Keke , Liu Lubin , Ren Yaping , Liu Fujun , Xue Junmiao , Hasanin Mohamed Sayed , Qi Hongzhao , Zhou Qihui
Published: June 2022

Inorganic nanoparticles (INPs) have been paid great attention in the field of oncology in recent past years since they have enormous potential in drug delivery, gene delivery, photodynamic therapy (PDT), photothermal therapy (PTT), bio-imaging, driven motion, etc. To overcome the innate limitations of the conventional INPs, such as fast elimination by the immune system, low accumulation in tumor sites, and severe toxicity to the organism, great efforts have recently been made to modify naked INPs, facilitating their clinical application. Taking inspiration from nature, considerable researchers have exploited cell membrane-camouflaged INPs (CMCINPs) by coating various cell membranes onto INPs. CMCINPs naturally inherit the surface adhesive molecules, receptors, and functional proteins from the original cell membrane, making them versatile as the natural cells. In order to give a timely and representative review on this rapidly developing research subject, we highlighted recent advances in CMCINPs with superior unique merits of various INPs and natural cell membranes for cancer therapy applications. The opportunity and obstacles of CMCINPs for clinical translation were also discussed. The review is expected to assist researchers in better eliciting the effect of CMCINPs for the management of tumors and may catalyze breakthroughs in this area.

Graphical Abstract
Research can be integrated into public health policy-making: global lessons for and from Spanish economic evaluations
Authors: Trapero-Bertran Marta , Pokhrel Subhash , Hanney Stephen
Published: June 2022

WHO promotes the use of research in policy-making to drive improvements in health, including in achieving Sustainable Development Goals such as tobacco control. The European Union’s new €95 billion Horizon Europe research framework programme parallels these aims, and also includes commitments to fund economic evaluations. However, researchers often express frustration at the perceived lack of attention to scientific evidence during policy-making. For example, some researchers claim that evidence regarding the return on investment from optimal implementation of evidence-based policies is frequently overlooked. An increasingly large body of literature acknowledges inevitable barriers to research use, but also analyses facilitators encouraging such use. This opinion piece describes how some research is integrated into policy-making. It highlights two recent reviews. One examines impact assessments of 36 multi-project research programmes and identifies three characteristics of projects more likely to influence policy-making. These include a focus on healthcare system needs, engagement of stakeholders, and research conducted for organizations supported by structures to receive and use evidence. The second review suggests that such characteristics are likely to occur as part of a comprehensive national health research system strategy, especially one integrated into the healthcare system. We also describe two policy-informing economic evaluations conducted in Spain. These examined the most cost-effective package of evidence-based tobacco control interventions and the cost-effectiveness of different strategies to increase screening coverage for cervical cancer. Both projects focused on issues of healthcare concern and involved considerable stakeholder engagement. The Spanish examples reinforce some lessons from the global literature and, therefore, could help demonstrate to authorities in Spain the value of developing comprehensive health research systems, possibly following the interfaces and receptor model. The aim of this would be to integrate needs assessment and stakeholder engagement with structures spanning the research and health systems. In such structures, economic evaluation evidence could be collated, analysed by experts in relation to healthcare needs, and fed into both policy-making as appropriate, and future research calls. The increasingly large local and global evidence base on research utilization could inform detailed implementation of this approach once accepted as politically desirable. Given the COVID-19 pandemic, increasing the cost-effectiveness of healthcare systems and return on investment of public health interventions becomes even more important.
Treatment with eFT-508 increases chemosensitivity in breast cancer cells by modulating the tumor microenvironment
Authors: Yang Zhao-ying , Jiang Cheng-wei , Zhang Wen-long , Sun Guang
Published: June 2022

Background

Patients with triple-negative breast cancer (TNBC) are better responders to neoadjuvant chemotherapy; however, they are poor in the durability of response with decreased overall and progression-free survival.

Methods

Given that significant improvements have been reported with PD-L1-PD-1 blockade in different cancers, we evaluated the in vitro and in vivo effectiveness of Tomivosertib (eFT-508), an anthracycline, adriamycin, and MNK1/2 inhibitor, which has been previously shown to inhibit translation of PD-L1 in mice model of liver cancer, alone or in combination using BC cell lines and an orthotopic xenograft mice model using the TNBC cell line MDA-MB-231.

Results

Within the context of The Cancer Genome Atlas (TCGA) dataset, expression of CD274 mRNA, which encodes programmed death-ligand 1 (PD-L1), was found to be significantly overexpressed in TNBC patients compared to patients with HER2 + or luminal breast cancer (BC). Even within TNBC sub-types, CD274 expression was significantly higher in the immune modulatory subtype (TNBC-IM).

BC cells exhibited high IC50 = 0.85 ± 0.07 nM with Adriamycin and significantly lower IC50 = 0.23 ± 0.04 nM with eFT-508 (P < 0.01). Combination treatment showed in vitro synergism on chemosensitivity. Combination therapy also exhibited a synergistic effect on inhibition of tumor growth and lung colonization in vivo. Mass cytometry-based evaluation of the tumor microenvironment revealed significant attenuation of both PD-L1 and PD-L2 following mono- or combination therapy with eFT-508.

Conclusions

Treatment with eFT-508 restored effector and cytotoxic function of tumor-infiltrating CD8 + T cells in mice. The remarkable efficacy observed both in vitro and in vivo, and clinical synergism with adriamycin, highlights the potential of eFT-508 as an alternative, yet more efficacious, therapeutic option for patients with TNBC.
Quality improvement in juvenile idiopathic arthritis: a mixed-methods implementation pilot of the CAPTURE-JIA dataset
Authors: McErlane Flora , Anderson Chris , Lawson-Tovey Saskia , Lee Barbara , Lee Chris , Lunt Laura , McDonagh Janet E. , Smith Andrew D. , Smith Nicola , Cleary Gavin
Published: June 2022

Background

A significant proportion of children and young people with juvenile idiopathic arthritis (JIA) do not achieve inactive disease during the first two years following diagnosis. Refinements to clinical care pathways have the potential to improve clinical outcomes but a lack of consistent and contemporaneous clinical data presently precludes standard setting and implementation of meaningful quality improvement programmes.

This study was the first to pilot clinical data collection and analysis using the CAPTURE-JIA dataset, and to explore patient and clinician-reported feasibility and acceptability data.

Methods

A multiphase mixed-methods approach enabled prospective collection of quantitative data to examine the feasibility and efficacy of dataset collection and of qualitative data informing the context and processes of implementation. An initial paper pilot informed the design of a bespoke electronic data collection system (the Agileware system), with a subsequent electronic pilot informing the final CAPTURE-JIA data collection tool.

Results

Paper collection of patient data was feasible but time-consuming in the clinical setting. Phase 1 paper pilot data (121 patients) identified three themes: problematic data items (14/62 data items received >40% missing data), formatting of data collection forms and a clinician-highlighted need for digital data collection, informing Phase 2 electronic data collection tool development. Patients and families were universally supportive of the collection and analysis of anonymised patient data to inform clinical care. No apparent preference for paper / electronic data collection was reported by families.

Phase 3 electronic pilot data (38 patients) appeared complete and the system reported to be easy to use. Analysis of the study dataset and a dummy longitudinal dataset confirmed that all eleven JIA national audit questions can be answered using the electronic system.

Conclusions

Multicentre CAPTURE-JIA data collection is feasible and acceptable, with a bespoke data collection system highlighted as the most satisfactory solution. The study is informing ongoing work towards a streamlined and flexible national paediatric data collection system to drive quality improvement in clinical care.
Monogenic disorders as mimics of juvenile idiopathic arthritis
Authors: Furness Laura , Riley Phil , Wright Neville , Banka Siddharth , Eyre Stephen , Jackson Adam , Briggs Tracy A.
Published: June 2022

Background

Juvenile idiopathic arthritis is the most common chronic rheumatic disease of childhood. The term JIA encompasses a heterogenous group of diseases. The variability in phenotype of patients affected by the disease means it is not uncommon for mimics of JIA to be misdiagnosed.

Case presentation

We present four cases who were treated in single tertiary rheumatology centre for JIA who were subsequently diagnosed with a rare monogenic disease. All four patients shared the unifying features of presenting in early childhood and subsequently suffered with refractory disease, not amenable to usual standards of treatment. Multicentric Carpotarsal Osteolysis Syndrome and Camptodactyly-arthropathy-coxa vara-pericarditis syndrome are non-inflammatory conditions and patients typically present with arthropathy, normal inflammatory markers and atypical radiological features. Blau syndrome is an autosomal dominant condition and patients will typically have symmetrical joint involvement with a strong family history of arthritis, signifying the genetic aetiology.

Conclusions

We share our learning from these cases to add to the growing portfolio of JIA mimics and to highlight when to consider an alternative diagnosis. In cases of refractory disease and diagnostic uncertainty further imaging and genetic testing can play a crucial role in establishing the aetiology. In all of these cases the correct diagnosis was made due to careful, longitudinal clinical phenotyping and a close working relationship between rheumatology, radiology and clinical genetics; highlighting the importance of the multidisciplinary team in managing complex patients.
Construction of the SHP-GLOX lignin regulation system and its application in rice straw
Authors: Wang Qingdong , Zhang Jiayuan , Li Yan , Wang Ran
Published: June 2022

Background

There is great productivity of rice(Oryza sativa L. spp. japonica) straw in China, which is a potential source of biomass for biofuel and forage. However, the high levels of lignins in rice straw limited its usage and induced the formation of agricultural waste. In order to modify the lignins contents to improve biofuel production and forage digestibility, we selected Soybean hull peroxidase (SHP) and Glyoxal oxidase (GLOX) as candidate genes to improve quality of rice straw. SHP, a class III plant peroxidase, is derived from multiple sources. It has several advantages, such as high resistance to heat, high stability under acidic and alkaline conditions, and a broad substrate range. SHP is speculated to be useful for lignin degradation. Glyoxal oxidase (GLOX) is an extracellular oxidase that can oxidize glyoxal and methylglyoxal in the extracellular medium to generate H2O2.

Results

In the present study, the SHP and GLOX genes in pCAMBIA3301-glycine-rich protein (GRP)-SHP-GLOX, designated the K167 vector, were optimized and introduced into rice embryos using Agrobacterium-mediated transformation. Positive transgenic rice embryos were examined using molecular, physiological, biochemical and fermentation tests. The outcomes suggested that SHP degraded lignin effectively.

Conclusions

This research has created a rice breeding material with normal growth and yield but stalks that are more amenable to degradation in the later stage for use in breeding rice varieties whose stalks are easily used for energy. Our results will improve the industrial and commercial applications of rice straw.