bluuebunny/crossref_metadata_2025 huggingface dataset:
Peroxiredoxin 6 mediates the protective function of curcumin pretreatment in acute lung injury induced by serum from patients undergoing one-lung ventilation in vitro
Authors: Li Hui-Ting , Tan Fang , Zhang Tian-Hua , Cao Long-Hui , Tan Hong-Ying , Lin Wen-Qian , Zeng Wei-An , Chi Xin-Jin
Published: May 2022

Background

Curcumin has attracted much attention due to its wide range of therapeutic effects. In this study, we used serum collected from patients undergoing one-lung ventilation (OLV) to establish an in vitro acute lung injury (ALI) model to explore the potential protective mechanism of curcumin on ALI. Our study provides a new reference for the prevention and treatment of ALI induced by OLV.

Methods

A549 cells were treated with 20% serum from patients undergoing OLV to establish an in vitro ALI model. Curcumin, at a dose of 40 μg/ml, was administered two hours prior to this model. The levels of inflammation and oxidative stress markers were observed by Western blot, qRT–PCR, ELISA and reactive oxygen species assay. Additionally, the expression of peroxiredoxin 6 (Prdx6) and proteins involved in the NF-κB signaling pathway was evaluated.

Results

Twenty percent of serum collected from patients undergoing OLV downregulated the expression of Prdx6, leading to the activation of the NF-κB signaling pathway, which was associated with the subsequent overproduction of inflammatory cytokines and reactive oxygen species. Pretreatment with curcumin restored Prdx6 downregulation and inhibited NF-κB pathway activation by suppressing the nuclear translocation of P65, eventually reducing inflammation and oxidative stress damage in A549 cells.

Conclusions

Prdx6 mediated the protective function of curcumin by inhibiting the activation of the NF-κB pathway in ALI in vitro.
Transtibial pull-out repair of lateral meniscus posterior root is beneficial for graft maturation after anterior cruciate ligament reconstruction: a retrospective study
Authors: Li Mengyuan , Li Zeng , Li Zezhen , Jiang Hai , Lee Soomin , Huang Wenhan , Zheng Qiujian
Published: May 2022

Purpose

To determine the repair of LMPR lesions would improve the ACL graft maturation.

Method

A total of 49 patients underwent ACL reconstruction were included in this study. Patients were furtherly sub-grouped according to the status of LMPR: intact (17), repair (16) and resected (16). Assessments performed pre- and 2 years post-operatively included patients-reported scores and arthrometer side-to-side difference. Magnetic resonance imaging was used 2 years after the surgery to compare the lateral meniscal extrusion (LME), anterior tibial subluxation of the medial compartment (ATSMC), anterior tibial subluxation of the lateral compartment (ATSLC), the difference of ATSMC and ATSLC, and signal/noise quotient (SNQ) of ACL graft.

Results

In LMPR resected group, it showed greater post-operative ATSMC-ATSLC difference when compared with pre-operatively (P = 0.006) and with the other 2 groups (intact: P = 0.031; repair: P = 0.048). SNQ of ACL graft was higher in LMPR resected group than those in LMPR intact (P = 0.004) and repair group (P = 0.002). The LMPR repair group showed significant reduction in LME post-operatively (P = 0.001). Post-operative measures on ATSLC-ATSMC difference (β = 0.304, P = 0.049) and LME (β = 0.492, P = 0.003) showed significant association with graft SNQ.

Conclusions

Transtibial repair of LMPR concomitant with ACL reconstruction restored translational stability, reduced meniscus extrusion, making it beneficial for ACL graft maturation.
Urdu translation and cross-cultural validation of Cumberland Ankle Instability Tool (CAIT)
Authors: Khan Basma , Ikram Mehwish , Rehman Syed Shakil ur , un Nisa Zaib
Published: May 2022

Background

The Cumberland Ankle Instability Tool (CAIT) is a self-assessment tool for people with chronic ankle instability (CAI). This tool had been translated and validated in many languages but there is no Urdu version of CAIT available.

Objective

The aim was to translate the CAIT into the Urdu Language and determine its validity and reliability.

Methods

A standardized step-wise forward and backward translation process was followed. Content, construct, convergent validity, internal consistency, and test–retest reliability were determined. A pilot study was done on 10 patients with CAI. The final version was investigated in 120 patients (mean age 26.6 ± 4.8 yrs) with CAI for validity and test–retest reliability in which 105 participants filled the questionnaire in the second week. Internal consistency was calculated by Cronbach’s alpha. Intraclass correlation (ICC2,1) was calculated to assess test–retest reliability between two weeks. Standard error of measurement (SEM) and smallest detectable change (SDC) were calculated. Convergent validity was determined by correlating Urdu CAIT with the Foot and Ankle Outcome Score (FAOS) using Spearman’s correlation co-efficient. Factor analysis describes the structure of underlying factors.

Results

Content validity index was > 0.80 of each question. Internal consistency was acceptable (Cronbach’s alpha > 0.75). Convergent validity with FAOS total score showed a moderate negative correlation (r = -0.68) with U-CAIT and negatively correlated with subscales of FAOS. Test–retest reliability was excellent ICC2,1 > 0.80. Scree plot showed 3 factors > 1eigen value.

Conclusion

The Urdu version of CAIT is a valid and reliable assessment tool for patients with chronic ankle instability. It has good content validity, construct validity and reliability.
Introduction of loxP sites by electroporation in the mouse genome; a simple approach for conditional allele generation in complex targeting loci
Authors: Bernas Guillaume , Ouellet Mariette , Barrios Andréa , Jamann Hélène , Larochelle Catherine , Lévy Émile , Schmouth Jean-François
Published: May 2022

Background

The discovery of the CRISPR-Cas9 system and its applicability in mammalian embryos has revolutionized the way we generate genetically engineered animal models. To date, models harbouring conditional alleles (i.e. two loxP sites flanking an exon or a critical DNA sequence of interest) are amongst the most widely requested project type that are challenging to generate as they require simultaneous cleavage of the genome using two guides in order to properly integrate the repair template. An approach, using embryo sequential electroporation has been reported in the literature to successfully introduce loxP sites on the same allele. Here, we describe a modification of this sequential electroporation procedure that demonstrated the production of conditional allele mouse models for eight different genes via one of two possible strategies: either by consecutive sequential electroporation (strategy A) or non-consecutive sequential electroporation (strategy B). This latest strategy originated from using the by-product produced when using consecutive sequential electroporation (i.e. mice with a single targeted loxP site) to complete the project.

Results

By using strategy A, we demonstrated successful generation of conditional allele models for three different genes (Icam1, Lox, and Sar1b), with targeting efficiencies varying between 5 and 13%. By using strategy B, we generated five conditional allele models (Loxl1, Pard6a, Pard6g, Clcf1, and Mapkapk5), with targeting efficiencies varying between 3 and 25%.

Conclusion

Our modified electroporation-based approach, involving one of the two alternative strategies, allowed the production of conditional allele models for eight different genes via two different possible paths. This reproducible method will serve as another reliable approach in addition to other well-established methodologies in the literature for conditional allele mouse model generation.
Serum liver enzymes and diabetes from the Rafsanjan cohort study
Authors: Noroozi Karimabad Mojgan , Khalili Parvin , Ayoobi Fatemeh , Esmaeili-Nadimi Ali , La Vecchia Carlo , jamali Zahra
Published: May 2022

Background

We evaluated the relation between ALT, AST, GGT and ALP with diabetes in the Rafsanjan Cohort Study.

Materials and methods

The present study is a cross-sectional research including 9991 adults participated via sampling. We used data obtained from the Rafsanjan Cohort Study (RCS), as a part of the prospective epidemiological research studies in IrAN (PERSIAN). Elevated serum levels of ALT, AST, GGT and ALP were defined according to the reference range of the laboratory in the cohort center. Serum liver enzymes levels within the normal range were categorized into quartiles, and their relationship with diabetes was evaluated by logistic regressions.

Findings

In present study, elevated serum levels of ALT, AST, GGT, and ALP were associated with increased odds of diabetes (adjusted ORs: 1.81, 95%CI 1.51–2.17; 1.75, 95%CI 1.32–2.32; 1.77, 95%CI 1.50–2.08; 1.60, 95%CI 1.35–1.90 respectively). Also, in subjects with normal levels of ALT, GGT and ALP, a dose–response increase was shown for diabetes.

Conclusion

Elevated levels of ALT, AST, GGT and ALP are related to a higher odds of diabetes. Also, increased levels of ALT, GGT and ALP even within normal range were independently related with the increased odds of diabetes. These results indicated the potential of elevated liver enzymes as biomarkers for the possible presence of diabetes.
Long-distance caregiving at the end of life: a protocol for an exploratory qualitative study in Germany
Authors: Herbst Franziska A. , Schneider Nils , Stiel Stephanie
Published: May 2022

Background

Of the approximately 4.7 million people in Germany caring for a relative, many live at a geographical distance from their loved one. The provision of remote care to a terminally ill patient is associated with specific challenges and burdens. In the German context, research is lacking on the specific experiences and needs of caregivers in end-of-life situations who are geographically distanced from their relative. Thus, the overarching goal of the proposed study is to detail the specifics of long-distance caregiving at the end of life in Germany, determining the role played by physical distance in shaping end-of-life caregiving and identifying the needs of long-distance caregivers in this situation.

Methods

The exploratory qualitative study will be guided by an inductive logic, drawing on one-time semi-structured interviews. To uncover the multiplicity of caregiving experiences, long-distance caregivers of both patients receiving early palliative care and patients at a very advanced stage of disease will be included. The study will be divided into five phases: (1) preparation and pretest, (2) data collection and primary analysis, (3) data analysis and interpretation, (4) advisory board workshop and (5) conclusions and recommendations.

Discussion

The study will aim at generating valuable insight regarding the experiences and needs of family caregivers of end-of-life patients. This is particularly relevant, given that families are becoming increasingly geographically dispersed. As this trend continues, it will challenge traditional models of family care and shed light on novel caregiving issues that will need to be addressed through social and health policy.

Trial registration

The study was prospectively registered in the German Clinical Trials Register (Deutsches Register Klinischer Studien) (Registration N° DRKS00024164; date of registration: January 25, 2021), and is searchable under the International Clinical Trials Registry Platform Search Portal of the World Health Organization, under the German Clinical Trials Register number.
Wild Egyptian medicinal plants show in vitro and in vivo cytotoxicity and antimalarial activities
Authors: Abdou Ahmed M. , Seddek Abdel-latif S. , Abdelmageed Noha , Badry Mohamed O. , Nishikawa Yoshifumi
Published: May 2022

Background

Medicinal plants have been successfully used as an alternative source of drugs for the treatment of microbial diseases. Finding a novel treatment for malaria is still challenging, and various extracts from different wild desert plants have been reported to have multiple medicinal uses for human public health, this study evaluated the antimalarial efficacy of several Egyptian plant extracts.

Methods

We assessed the cytotoxic potential of 13 plant extracts and their abilities to inhibit the in vitro growth ofPlasmodium falciparum(3D7), and to treat infection with non-lethalPlasmodium yoelii17XNL in an in vivo malaria model in BALB/c mice.

Results

In vitro screening identified four promising candidates,Trichodesma africanum, Artemisia judaica, Cleome droserifolia, andVachellia tortilis, with weak-to-moderate activity againstP. falciparumerythrocytic blood stages with mean half-maximal inhibitory concentration 50 (IC50) of 11.7 μg/ml, 20.0 μg/ml, 32.1 μg/ml, and 40.0 μg/ml, respectively. Their selectivity index values were 35.2, 15.8, 11.5, and 13.8, respectively. Among these four candidates,T. africanumcrude extract exhibited the highest parasite suppression in a murine malaria model againstP. yoelii.

Conclusion

Our study identified novel natural antimalarial agents of plant origin that have potential for development into therapeutics for treating malaria.
Quality of knee osteoarthritis care in the Netherlands: a survey on the perspective of people with osteoarthritis
Authors: Oomen J. M. H. , Peters Y. A. S. , van den Ende C. H. , Schers H. J. , Assendelft W. J. J. , Vriezekolk J. E. , Koëter S.
Published: May 2022

Background

Quality indicators (QIs) are used to monitor quality of care and adherence to osteoarthritis (OA) standards of care. Patient reported QIs can identify the most important gaps in quality of care and the most vulnerable patient groups. The aim of this study was to capture the perspective of people with knee OA (KOA) in the Netherlands on the quality of care received, and explore determinants related to lower achievement rates.

Methods

We sent an online survey to all members of The Dutch Knee Panel (n = 622) of the Sint Maartenskliniek Nijmegen, the Netherlands between September and October 2019. The survey consisted of a slightly adapted version of the “OsteoArthritis Quality Indicator” (OA-QI) questionnaire (18 items; yes, no, N/A); a rating of quality of KOA care on a 10-point scale; a question on whether or not one wanted to see change in the care for KOA; and an open-ended question asking recommendations for improvement of OA care. Furthermore, sociodemographic and disease related characteristics were collected. Pass rates for separate QIs and pass rates on patient level were calculated by dividing the number of times the indicator was achieved by the number of eligible persons for that particular indicator.

Results

A total of 434 participants (70%) completed the survey. The mean (SD) pass rate (those answering “Yes”) for separate QIs was 49% (20%); ranging from 15% for receiving referral for weight reduction to 75% for patient education on how to manage knee OA. The mean (SD) pass rate on patient level was 52% (23%). Presence of OA in other joints, comorbidities, and having a knee replacement were associated with higher pass rates. On average, a score of 6.5 (1.6) was given for the quality of care received, and the majority of respondents (59%) wanted change in the care for KOA. Of 231 recommendations made, most often mentioned were the need for tailoring of care (14%), more education (13%), and more empathy and support from healthcare providers (12%).

Conclusion

This study found patients are only moderately satisfied with the OA care received, and showed substantial gaps between perceived quality of care for OA and internationally accepted standards. Future research should focus on the underlying reasons and provide strategies to bridge these gaps.
Diet of Mesozoic toothed birds (Longipterygidae) inferred from quantitative analysis of extant avian diet proxies
Authors: Miller Case Vincent , Pittman Michael , Wang Xiaoli , Zheng Xiaoting , Bright Jen A.
Published: May 2022

Background

Birds are key indicator species in extant ecosystems, and thus we would expect extinct birds to provide insights into the nature of ancient ecosystems. However, many aspects of extinct bird ecology, particularly their diet, remain obscure. One group of particular interest is the bizarre toothed and long-snouted longipterygid birds. Longipterygidae is the most well-understood family of enantiornithine birds, the dominant birds of the Cretaceous period. However, as with most Mesozoic birds, their diet remains entirely speculative.

Results

To improve our understanding of longipterygids, we investigated four proxies in extant birds to determine diagnostic traits for birds with a given diet: body mass, claw morphometrics, jaw mechanical advantage, and jaw strength via finite element analysis. Body mass of birds tended to correspond to the size of their main food source, with both carnivores and herbivores splitting into two subsets by mass: invertivores or vertivores for carnivores, and granivores + nectarivores or folivores + frugivores for herbivores. Using claw morphometrics, we successfully distinguished ground birds, non-raptorial perching birds, and raptorial birds from one another. We were unable to replicate past results isolating subtypes of raptorial behaviour. Mechanical advantage was able to distinguish herbivorous diets with particularly high values of functional indices, and so is useful for identifying these specific diets in fossil taxa, but overall did a poor job of reflecting diet. Finite element analysis effectively separated birds with hard and/or tough diets from those eating foods which are neither, though could not distinguish hard and tough diets from one another. We reconstructed each of these proxies in longipterygids as well, and after synthesising the four lines of evidence, we find all members of the family butShengjingornis(whose diet remains inconclusive) most likely to be invertivores or generalist feeders, with raptorial behaviour likely inLongipteryxandRapaxavis.

Conclusions

This study provides a 20% increase in quantitatively supported fossil bird diets, triples the number of diets reconstructed in enantiornithine species, and serves as an important first step in quantitatively investigating the origins of the trophic diversity of living birds. These findings are consistent with past hypotheses that Mesozoic birds occupied low trophic levels.
Structured reporting to improve transparency of analyses in prognostic marker studies
Authors: Sauerbrei Willi , Haeussler Tim , Balmford James , Huebner Marianne
Published: May 2022

Background

Factors contributing to the lack of understanding of research studies include poor reporting practices, such as selective reporting of statistically significant findings or insufficient methodological details. Systematic reviews have shown that prognostic factor studies continue to be poorly reported, even for important aspects, such as the effective sample size. The REMARK reporting guidelines support researchers in reporting key aspects of tumor marker prognostic studies. The REMARK profile was proposed to augment these guidelines to aid in structured reporting with an emphasis on including all aspects of analyses conducted.

Methods

A systematic search of prognostic factor studies was conducted, and fifteen studies published in 2015 were selected, three from each of five oncology journals. A paper was eligible for selection if it included survival outcomes and multivariable models were used in the statistical analyses. For each study, we summarized the key information in a REMARK profile consisting of details about the patient population with available variables and follow-up data, and a list of all analyses conducted.

Results

Structured profiles allow an easy assessment if reporting of a study only has weaknesses or if it is poor because many relevant details are missing. Studies had incomplete reporting of exclusion of patients, missing information about the number of events, or lacked details about statistical analyses, e.g., subgroup analyses in small populations without any information about the number of events. Profiles exhibit severe weaknesses in the reporting of more than 50% of the studies. The quality of analyses was not assessed, but some profiles exhibit several deficits at a glance.

Conclusions

A substantial part of prognostic factor studies is poorly reported and analyzed, with severe consequences for related systematic reviews and meta-analyses. We consider inadequate reporting of single studies as one of the most important reasons that the clinical relevance of most markers is still unclear after years of research and dozens of publications. We conclude that structured reporting is an important step to improve the quality of prognostic marker research and discuss its role in the context of selective reporting, meta-analysis, study registration, predefined statistical analysis plans, and improvement of marker research.
Palbociclib-based high-throughput combination drug screening identifies synergistic therapeutic options in HPV-negative head and neck squamous cell carcinoma
Authors: Gu Ziyue , Shi Chaoji , Li Jiayi , Han Yong , Sun Bao , Zhang Wuchang , Wu Jing , Zhou Guoyu , Ye Weimin , Li Jiang , Zhang Zhiyuan , Zhou Rong
Published: May 2022

Background

Deregulation of cell-cycle pathway is ubiquitously observed in human papillomavirus negative (HPVneg) head and neck squamous cell carcinoma (HNSCC). Despite being an attractive target, CDK4/6 inhibition using palbociclib showed modest or conflicting results as monotherapy or in combination with platinum-based chemotherapy or cetuximab in HPVneg HNSCC. Thus, innovative agents to augment the efficacy of palbociclib in HPVneg HNSCC would be welcomed.

Methods

A collection of 162 FDA-approved and investigational agents was screened in combinatorial matrix format, and top combinations were validated in a broader panel of HPVneg HNSCC cell lines. Transcriptional profiling was conducted to explore the molecular mechanisms of drug synergy. Finally, the most potent palbociclib-based drug combination was evaluated and compared with palbociclib plus cetuximab or cisplatin in a panel of genetically diverse HPVneg HNSCC cell lines and patient-derived xenograft models.

Results

Palbociclib displayed limited efficacy in HPVneg HNSCC as monotherapy. The high-throughput combination drug screening provided a comprehensive palbociclib-based drug-drug interaction dataset, whereas significant synergistic effects were observed when palbociclib was combined with multiple agents, including inhibitors of the PI3K, EGFR, and MEK pathways. PI3K pathway inhibitors significantly reduced cell proliferation and induced cell-cycle arrest in HPVneg HNSCC cell lines when combined with palbociclib, and alpelisib (a PI3Kα inhibitor) was demonstrated to show the most potent synergy with particularly higher efficacy in HNSCCs bearing PIK3CA alterations. Notably, when compared with cisplatin and cetuximab, alpelisib exerted stronger synergism in a broader panel of cell lines. Mechanistically, RRM2-dependent epithelial mesenchymal transition (EMT) induced by palbociclib, was attenuated by alpelisib and cetuximab rather than cisplatin. Subsequently, PDX models with distinct genetic background further validated that palbociclib plus alpelisib had significant synergistic effects in models harboring PIK3CA amplification.

Conclusions

This study provides insights into the systematic combinatory effect associated with CDK4/6 inhibition and supports further initiation of clinical trials using the palbociclib plus alpelisib combination in HPVneg HNSCC with PIK3CA alterations.
Preclinical validation and phase I trial of 4-hydroxysalicylanilide, targeting ribonucleotide reductase mediated dNTP synthesis in multiple myeloma
Authors: Xie Yongsheng , Wang Yingcong , Xu Zhijian , Lu Yumeng , Song Dongliang , Gao Lu , Yu Dandan , Li Bo , Chen Gege , Zhang Hui , Feng Qilin , Zhang Yong , Hu Ke , Huang Cheng , Peng Yu , Wu Xiaosong , Mao Zhiyong , Shao Jimin , Zhu Weiliang , Shi Jumei
Published: May 2022

Background

Aberrant DNA repair pathways contribute to malignant transformation or disease progression and the acquisition of drug resistance in multiple myeloma (MM); therefore, these pathways could be therapeutically exploited. Ribonucleotide reductase (RNR) is the rate-limiting enzyme for the biosynthesis of deoxyribonucleotides (dNTPs), which are essential for DNA replication and DNA damage repair. In this study, we explored the efficacy of the novel RNR inhibitor, 4-hydroxysalicylanilide (HDS), in myeloma cells and xenograft model. In addition, we assessed the clinical activity and safety of HDS in patients with MM.

Methods

We applied bioinformatic, genetic, and pharmacological approaches to demonstrate that HDS was an RNR inhibitor that directly bound to RNR subunit M2 (RRM2). The activity of HDS alone or in synergy with standard treatments was evaluated in vitro and in vivo. We also initiated a phase I clinical trial of single-agent HDS in MM patients (ClinicalTrials.gov: NCT03670173) to assess safety and efficacy.

Results

HDS inhibited the activity of RNR by directly targeting RRM2. HDS decreased the RNR-mediated dNTP synthesis and concomitantly inhibited DNA damage repair, resulting in the accumulation of endogenous unrepaired DNA double-strand breaks (DSBs), thus inhibiting MM cell proliferation and inducing apoptosis. Moreover, HDS overcame the protective effects of IL-6, IGF-1 and bone marrow stromal cells (BMSCs) on MM cells. HDS prolonged survival in a MM xenograft model and induced synergistic anti-myeloma activity in combination with melphalan and bortezomib. HDS also showed a favorable safety profile and demonstrated clinical activity against MM.

Conclusions

Our study provides a rationale for the clinical evaluation of HDS as an anti-myeloma agent, either alone or in combination with standard treatments for MM.

Trial registration: ClinicalTrials.gov, NCT03670173, Registered 12 September 2018.
Increased frequency of proangiogenic tunica intima endothelial kinase 2 (Tie2) expressing monocytes in individuals with type 2 diabetes mellitus
Authors: Reijrink M. , van Ark J. , Lexis C. P. H. , Visser L. M. , Lodewijk M. E. , van der Horst I. C. C. , Zeebregts C. J. , van Goor H. , de Jager S. C. A. , Pasterkamp G. , Wolffenbuttel B. H. R. , Hillebrands J. L.
Published: May 2022

Background

Individuals with type 2 diabetes mellitus (T2DM) have an increased risk for developing macrovascular disease (MVD) manifested by atherosclerosis. Phenotypically and functionally different monocyte subsets (classical; CD14++CD16−, non-classical; CD14+CD16++, and intermediate; CD14++CD16+) including pro-angiogenic monocytes expressing Tie2 (TEMs) can be identified. Here we investigated monocyte heterogeneity and its association with T2DM and MVD.

Methods

Individuals with (N = 51) and without (N = 56) T2DM were recruited and allocated to "non-MVD" or "with MVD" (i.e., peripheral or coronary artery disease) subgroups. Blood monocyte subsets were quantified based on CD14, CD16 and Tie2 expression levels. Plasma levels of Tie2-ligands angiopoietin-1 and angiopoietin-2 were determined using ELISA. Carotid endarterectomy samples from individuals with (N = 24) and without (N = 22) T2DM were stained for intraplaque CD68+ macrophages (inflammation) and CD34+ (angiogenesis), as plaque vulnerability markers.

Results

Monocyte counts were similar between individuals with T2DM and healthy controls (non-diabetic, non-MVD). Non-classical monocytes were reduced (p < 0.05) in T2DM, whereas the percentage of TEMs within the intermediate subset was increased (p < 0.05). T2DM was associated with increased angiopoietin-1 (p < 0.05) and angiopoietin-2 (p = 0.0001) levels. Angiopoietin-2 levels were higher in T2DM individuals with MVD compared with non-MVD (p < 0.01). Endarterectomized plaques showed no differences in macrophage influx and microvessel number between individuals with and without T2DM.

Conclusions

Monocyte subset distribution is altered in T2DM with reduced non-classical monocytes and increased TEM percentage in the intermediate monocyte subset. Increased angiopoietin-2 levels together with increased frequency of TEMs might promote plaque vulnerability in T2DM which could however not be confirmed at tissue level in advanced atherosclerotic lesions.
Major dietary patterns in relation to chronic low back pain; a cross-sectional study from RaNCD cohort
Authors: Pasdar Yahya , Hamzeh Behrooz , Karimi Sheno , Moradi Shima , Cheshmeh Sahar , Shamsi Mohammad Bagher , Najafi Farid
Published: May 2022

Background

Chronic low back pain (LBP) is the most common musculoskeletal pain that affects a person’s daily activities. This present study aimed at evaluating the relationship between major dietary pattern and Chronic LBP.

Methods

This cross-sectional analysis was examined 7686 Kurdish adults. The RaNCD cohort study physician diagnosed chronic LBP. Dietary patterns were derived using principal component analysis. The three identified dietary patterns derived were named: 1) the vegetarian diet included vegetables, whole grain, legumes, nuts, olive, vegetable oil, fruits, and fruit juice; 2) high protein diet related to higher adherence to red and white meat, legumes, nuts, and egg; and 3) energy-dense diet characterized with higher intake of salt, sweet, dessert, hydrogenated fat, soft drink, refined grain, tea, and coffee. Dietary pattern scores were divided into tertiles. Binary logistic regression in crude, adjusted odds ratios (OR) and 95% confidence intervals (CI) were used to determine this association.

Results

Twenty-two per cent of participants had chronic LBP. Higher adherence to high protein dietary pattern was inversely associated with chronic LBP in crude (OR: 0.79, 95% CI: 0.69–0.9) and adjusted model (for age, sex, smoking, drinking, diabetes, physical activity, body mass index, and waist circumference) (OR: 0.84, 95% CI: 0.72–0.97). In addition, after controlling for the mentioned potential confounders, participants in the highest category of energy dense diet were positively associated with chronic LBP compared with those in the lowest category (OR: 1.13, 95% CI: 1.01–1.32).

Conclusions

Higher adherence to the high protein diet was inversely related to chronic LBP prevalence. In addition, we found that following energy dense diet was positively associated with chronic LBP.
All-in-one approaches for triple-negative breast cancer therapy: metal-phenolic nanoplatform for MR imaging-guided combinational therapy
Authors: Xie Qi , Li Shichao , Feng Xingxing , Shi Jingyu , Li Yang , Yuan Guanjie , Yang Conglian , Shen Yaqi , Kong Li , Zhang Zhiping
Published: May 2022

Background

Conventional chemotherapy has poor efficacy in triple-negative breast cancer (TNBC) which is highly heterogeneous and aggressive. Imaging-guided therapy is usually combined with diverse treatment modalities, could realize the integration of diagnosis and treatments. Therefore, the primary challenge for combinational therapy is designing proper delivery systems to accomplish multiple synergistic effects.

Results

Herein, a facile nanoplatform was manufactured to fulfill the all-in-one approaches for TNBC combinational therapy. Fe3+-based metal-phenolic networks (MPNs) with bovine serum albumin (BSA) modification served as drug delivery carriers to encapsulate bleomycin (BLM), forming BFE@BSA NPs. The self-assembly mechanism, pH-responsive drug release behavior, and other physicochemical properties of this system were characterized. The potential of BFE@BSA NPs as photothermal transduction agents and magnetic resonance imaging (MRI) contrast agents was explored. The synergistic anti-tumor effects consisting of BLM-induced chemotherapy, Fenton reactions-mediated chemodynamic therapy, and photothermal therapy-induced apoptosis were studied both in vitro and in vivo. Once internalized into tumor cells, released BLM could cause DNA damage, while Fenton reactions were initiated to produce highly toxic •OH. Upon laser irradiation, BFE@BSA NPs could convert light into heat to achieve synergistic effects. After intravenous administration, BFE@BSA NPs exhibited great therapeutic effects in 4T1 tumor xenograft model. Moreover, as T1-weighted MRI contrast agents, BFE@BSA NPs could provide diagnosis and treatment monitoring for individualized precise therapy.

Conclusions

A nano-system that integrated imaging and combinational therapy (chemotherapy, chemodynamic therapy and photothermal therapy) were developed to kill the tumor and monitor therapeutic efficacy. This strategy provided an all-in-one theranostic nanoplatform for MRI-guided combinational therapy against TNBC.

Graphical Abstract
Vision-related quality of life in patients with glaucoma: the role of illness perceptions
Authors: Zhang Qiqi , Zhou Wenzhe , Song Di , Xie Yanqian , Lin Hao , Liang Youping , Ren Yanhan , Liang Yuanbo , Chen Yanyan
Published: May 2022

Purpose

To explore the predictive effects of illness perceptions on vision-related quality of life (VRQoL) in Chinese glaucoma patients.

Methods

In this cross-sectional study, 97 patients with glaucoma completed the brief illness perception questionnaire (BIPQ), the glaucoma quality of life-15 (GQL-15) questionnaire, and a questionnaire regarding sociodemographic and clinical information. A correlation analysis and hierarchical linear regression analysis were performed.

Results

The BIPQ total score was positively correlated with the total score of the GQL-15 questionnaire and the scores of its four dimensions. Chronic comorbidities, the type of glaucoma, the best-corrected visual acuity (BCVA), the mean defect (MD) of visual field in the better eye, and identity in the BIPQ were critical predictors of VRQoL. Illness perceptions independently accounted for 7.8% of the variance in the VRQoL of glaucoma patients.

Conclusions

Patients with stronger illness perceptions and those who perceive themselves as having more glaucoma symptoms are likely to experience worse VRQoL. Illness perceptions in glaucoma patients deserve clinical attention, and further studies are needed to examine whether cognitive interventions targeting illness perceptions can improve VRQoL.
Assessing competence of mid-level providers delivering primary health care in India: a clinical vignette-based study in Chhattisgarh state
Authors: Garg Samir , Tripathi Narayan , Datla Jayathra , Zapata Tomas , Mairembam Dilip S. , Bebarta Kirtti K. , Krishnendhu C. , de Graeve Hilde
Published: May 2022

Background

The global commitment to primary health care (PHC) has been reconfirmed in the declaration of Astana, 2018. India has also seen an upswing in national commitment to implement PHC. Health and wellness centres (HWCs) have been introduced, one at every 5000 population, with the fundamental purpose of bringing a comprehensive range of primary care services closer to where people live. The key addition in each HWC is of a mid-level healthcare provider (MLHP). Nurses were provided a 6-month training to play this role as community health officers (CHOs). But no assessments are available of the clinical competence of this newly inducted cadre for delivering primary care. The current study was aimed at providing an assessment of competence of CHOs in the Indian state of Chhattisgarh.

Methods

The assessment involved a comparison of CHOs with rural medical assistants (RMAs) and medical officers (MO), the two main existing clinical cadres providing primary care in Chhattisgarh. Standardized clinical vignettes were used to measure knowledge and clinical reasoning of providers. Ten ailments were included, based on primary care needs in Chhattisgarh. Each part of clinical vignettes was standardized using expert consultations and standard treatment guidelines. Sample size was adequate to detect 15% difference between scores of different cadres and the assessment covered 132 CHOs, 129 RMAs and 50 MOs.

Results

The overall mean scores of CHOs, RMAs and MOs were 50.1%, 63.1% and 68.1%, respectively. They were statistically different (p < 0.05). The adjusted model also confirmed the above pattern. CHOs performed well in clinical management of non-communicable diseases and malaria. CHOs also scored well in clinical knowledge for diagnosis. Around 80% of prescriptions written by CHOs for hypertension and diabetes were found correct.

Conclusion

The non-physician MLHP cadre of CHOs deployed in rural facilities under the current PHC initiative in India exhibited the potential to manage ambulatory care for illnesses. Continuous training inputs, treatment protocols and medicines are needed to improve performance of MLHPs. Making comprehensive primary care services available close to people is essential to PHC and well-trained mid-level providers will be crucial for making it a reality in developing countries.
The ROCK-ezrin signaling pathway mediates LPS-induced cytokine production in pulmonary alveolar epithelial cells
Authors: Ding Ning , Li Pibao , Li Huiqing , Lei Yunlong , Zhang Zengzhen
Published: May 2022

Background

Ezrin/radixin/moesin (ERM) proteins are members of the protein 4.1 superfamily and function as linkers that connect the actin cytoskeleton to the plasma membrane of cells. ERM also play critical role in the Lipopolysaccharide (LPS)-induced inflammatory response. However, the signaling mechanisms involved in this process remain unclear. In this study, we aimed to investigate the potential role of the rho-associated coiled-coil containing protein kinase (ROCK) pathway in LPS-induced ezrin phosphorylation and cytokine production in pulmonary alveolar epithelial cells.

Methods

Cultured A549 and HPAEpiC cells were treated with LPS. The expression and localization of ezrin in A549 and HPAEpiC cells were then analyzed by western blotting and immunoflurescence. Activation of RhoA/ROCK was assessed by western blotting and RhoA activity assays. The interaction of ezrin with Syk and myeloid differentiation factor 88 (MyD88)/IL-1R-associated kinase 1 (IRAK-1) was investigated by co-immunoprecipitation. The activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) was measured with electrophoretic mobility shift assays and by western blotting. ELISA and western blotting were performed to detect the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and high mobility group box 1 protein (HMGB1) release into the culture supernatant, and cellular HMGB1 levels.

Results

LPS induced ezrin phosphorylation in a concentration- and time-dependent manner. The blockade of RhoA/ROCK inhibited LPS-induced ezrin phosphorylation and its translocation from the cytoplasm to the cell membrane. Co-immunoprecipitation assays further revealed that ezrin associated with Syk constitutively, but only associated with MyD88/IRAK-1 upon LPS challenge. Moreover, LPS-induced p38 and nuclear NF-κB activation was found to be ezrin dependent. The suppression of ezrin by siRNA or the blockade of ROCK activation with Y-27632 reduced the production of TNF-α, IL-1β, and HMGB1 in response to LPS.

Conclusions

Our findings reveal a novel regulatory mechanism involving ezrin in the LPS-induced production of pro-inflammatory cytokines, and highlight the importance of the RhoA/ROCK-ezrin/Syk-MyD88/IRAK1 axis. Data presented in this manuscript provide novel insights into the signaling pathways activated in pulmonary alveolar epithelial cells by LPS.
A multilevel mixed effect analysis of neighbourhood and individual level determinants of risky sexual behaviour among young people in South Africa
Authors: Odimegwu Clifford Obby , Ugwu Nebechukwu Henry
Published: May 2022

Background

Despite national and international commitments and efforts to prevent risky sexual behaviours, a high proportion of young people in South Africa are engaged in risky sexual behaviour. However, most efforts are currently directed toward addressing individual-level factors at the expense of not addressing neighbourhood-level determinants such as social disorganisation, contributing to risky sexual behaviour among young people in South Africa. This study investigated the multilevel factors of risky sexual behaviours among young people by gender in South Africa, using the lens of socio-ecological and social disorganisation frameworks.

Methods

Data from a nationally representative sample of 1268 males and 2621 females aged 15–24 years, giving a total of, 3889 never-married youths, were drawn from the 2016 South Africa Demographic and Health Survey. Analysis was conducted using multilevel mixed-effect logistic regressions with random community-level effects.

Results

Findings show that youth who were from a heterogeneous ethnic group (AOR = 0.49, CI: 0.35–0.67), household size of 5 + members (AOR = 0.78, CI: 0.54–1.15), community education (AOR = 0.97, CI: 0.72–1.32) were associated with low engagement in multiple sexual partnerships. Youths who were employed (AOR = 0.84, CI: 0.59–1.18), and from high-level community poverty (AOR = 0.76, CI: 0.58–1.00) were also associated with reduced odds of unprotected sex. In addition, older youth aged 20–24 years (AOR = 12.6, CI: 9.93–16.00); secondary education attainment (AOR = 1.01, CI 0.58–1.77); family structure (AOR = 1.37, CI: 0.75–1.15); Gauteng province (AOR = 1.45 CI: 0.92–2.28); residential mobility (AOR = 1.25, CI: 1.02–1.53), community media exposure to contraceptives (unprotected sex) (AOR = 1.38, CI: 1.09–1.76) were more likely to engage in risky sexual behaviour.

Conclusion

The study revealed that neighbourhood and individual-level factors were important in explaining the factors associated with risky sexual behaviour among young people in South Africa. In addition, engagement in risky sexual behaviour was high, with minimal variation among young females and males in South Africa. It specifies that the practice of risky sexual behaviour is significantly associated with multilevel factors of social disorganisation that cut across gender. These results imply that there is a need to review policies of sexual risks reduction for each gender, which might help mitigate the adverse effects of social disorganisation for women and men youths in South Africa.
Characterizing the relationship between peak assistance torque and metabolic cost reduction during running with ankle exoskeletons
Authors: Miller Delaney E. , Tan Guan Rong , Farina Emily M. , Sheets-Singer Alison L. , Collins Steven H.
Published: May 2022

Background

Reducing the energy cost of running with exoskeletons could improve enjoyment, reduce fatigue, and encourage participation among novice and ageing runners. Previously, tethered ankle exoskeleton emulators with offboard motors were used to greatly reduce the energy cost of running with powered ankle plantarflexion assistance. Through a process known as “human-in-the-loop optimization”, the timing and magnitude of assistance torque was optimized to maximally reduce metabolic cost. However, to achieve the maximum net benefit in energy cost outside of the laboratory environment, it is also necessary to consider the tradeoff between the magnitude of device assistance and the metabolic penalty of carrying a heavier, more powerful exoskeleton.

Methods

In this study, tethered ankle exoskeleton emulators were used to characterize the effect of peak assistance torque on metabolic cost during running. Three recreational runners participated in human-in-the-loop optimization at four fixed peak assistance torque levels to obtain their energetically optimal assistance timing parameters at each level.

Results

We found that the relationship between metabolic rate and peak assistance torque was nearly linear but with diminishing returns at higher torque magnitudes, which is well-approximated by an asymptotic exponential function. At the highest assistance torque magnitude of 0.8 Nm/kg, participants’ net metabolic rate was 24.8 ± 2.3% (p = 4e–6) lower than running in the unpowered devices. Optimized timing of peak assistance torque was as late as allowed during stance (80% of stance) and optimized timing of torque removal was at toe-off (100% of stance); similar assistance timing was preferred across participants and torque magnitudes.

Conclusions

These results allow exoskeleton designers to predict the energy cost savings for candidate devices with different assistance torque capabilities, thus informing the design of portable ankle exoskeletons that maximize net metabolic benefit.
Evaporative flux method of leaf hydraulic conductance estimation: sources of uncertainty and reporting format recommendation
Authors: Wang Xiaoxiao , Zhao Jinfang , Huang Jianliang , Peng Shaobing , Xiong Dongliang
Published: May 2022

Background

The accurate estimation of leaf hydraulic conductance (Kleaf) is important for revealing leaf physiological characteristics and function. However, the Kleaf values are largely incomparable in previous studies for a given species indicating some uncertain influencing factors in Kleaf measurement.

Result

We investigated the potential impacts of plant sampling method, measurement setup, environmental factors, and transpiration steady state identification on Kleaf estimation in Oryza sativa and Cinnamomum camphora using evaporation flux method (EFM). The effects of sampling and rehydration time, the small gravity pressure gradients between water sources and leaves, and water degassing on Kleaf estimation were negligible. As expected, the estimated steady flow rate (E) was significantly affected by multiple environmental factors including airflow around leaf, photosynthetically active radiation (PARa) on leaf surfaces and air temperature. Kleaf decreased by 40% when PARa declined from 1000 to 500 µmol m−2 s−1 and decreased by 15.1% when air temperature increased from 27 to 37 °C. In addition, accurate steady-state flow rate identification and leaf water potential measurement were important for Kleaf estimation.

Conclusions

Based on the analysis of influencing factors, we provided a format for reporting the metadata of EFM-based Kleaf to achieve greater comparability among studies and interpretation of differences.