bluuebunny/crossref_metadata_2025 huggingface dataset:
Cervical cancer screening-related knowledge among community health workers in Eswatini: a cross-sectional survey
Authors: Khumalo Phinda G , Carey Mariko , Mackenzie Lisa , Sanson-Fisher Rob
Published: August 2022

Eswatini has the highest age-standardized incidence and second highest mortality rate related to cervical cancer globally. In Eswatini, community health workers educate communities about cervical cancer screening. They need to have accurate knowledge about cervical cancer and screening to do this effectively. Therefore, the current study aimed to assess knowledge regarding cervical cancer screening among community health workers in Eswatini. A telephone survey of 172 community health workers from eight selected constituencies was conducted. Descriptive analyses were performed to assess participants’ socio-demographic and service-related characteristics. Linear regression was applied to investigate factors associated with cervical cancer screening-related knowledge. One hundred and seven (62%) participants answered at least 80% of the questions correctly. However, knowledge regarding cervical cancer risk factors, the meaning of screening results and Eswatini cervical cancer screening guidelines was suboptimal. Community health workers aged 46–55 were more likely (β = 1.27, 95% confidence interval [CI]: 0.39–2.15, p < 0.01) to have a higher cervical cancer screening knowledge score than those aged 30–45 years. Community health workers from Lubombo were marginally less likely (β = −0.83, 95% CI: −1.80 to −0.04, p = 0.05) to have a higher knowledge score than those from Hhohho. This study suggests knowledge deficits amongst community health workers in Eswatini. Knowledge deficits may result in inaccurate information being communicated to clients. While increasing knowledge of these vital health workers may not be sufficient to increase cervical cancer screening rates in Eswatini, it is an essential first step that should be the focus of future educational efforts.
Ecological risk assessment of a pelagic seabird species in artisanal tuna fisheries
Authors: García-Barón Isabel , Granado Igor , Astarloa Amaia , Boyra Guillermo , Rubio Anna , Fernandes-Salvador José A , Zarauz Lucía , Onandia Iñigo , Mugerza Estanis , Louzao Maite
Published: August 2022

Fishery bycatch is a serious threat to several protected, endangered, and threatened species (PETs), requiring urgent action to develop and implement conservation measures. This study performs an Ecological Risk Assessment for the Effects of Fishing (ERAEF) using a spatially and temporally Productivity–Susceptibility Analysis (PSA) to calculate the potential risk to great shearwaters (Ardenna gravis) from direct interaction with the metiers of the artisanal tuna fishing fleet at the Bay of Biscay (baitboats and trollers). The PSA incorporates productivity attributes based on the Fecundity Factor Index; and susceptibility attributes calculated from the species spatio-temporal abundance patterns obtained developing density surface models and distribution and intensity of fishing activity based on pooled Vessel Monitoring System and logbook data. The PSA shows an overall moderate risk to great shearwaters by the artisanal tuna fishery also revealing that baitboats are less risky than trollers (risk score of 3.12 ± 0.09 and 2.70 ± 0.05, respectively). Spatially, the likelihood of presence of high potential risk areas was associated with prey availability for both the PET and the commercial fish species. The systematic, repeatable, and standardized ERAEF followed in this study can be used to advice for ecosystem-based fisheries management to improve management measures for reducing bycatch of PETs around the world.
Intoxications in an Australian Emergency Department Involving ‘Nitazene’ Benzylbenzimidazole Synthetic Opioids (Etodesnitazene, Butonitazene and Protonitazene)
Authors: Schumann Jennifer L , Syrjanen Rebekka , Alford Katherine , Mashetty Srujana , Castle Jared W , Rotella Joe , Maplesden Jacqueline , Greene Shaun L
Published: August 2022

Benzimidazole synthetic opioids are highly potent μ-opioid receptor agonists with heroin-like effects, including dose-dependent respiratory depression and a high risk of abuse and toxicity. Benzimidazoles were first detected in 2019 in Europe and Canada, with analytical confirmation of etodesnitazene, protonitazene and butonitazene in 2021. We report the first detections of these compounds in Australia, in two patients presenting with drug toxicity to Emergency Departments (EDs) in the state of Victoria. Case 1 was a female in her 20s who rectally administered etodesnitazene and was found unconscious with respiratory depression and hypotension. Case 2 was a female in her 30s who presented to the ED in a sedated state after taking a formulation of protonitazene that also contained butonitazene, in addition to methylamphetamine. She responded positively to naloxone. Novel synthetic opioids were used with prior experience of the formulations purchased; however, the unpredictability of their effects was demonstrated by the acute toxicity experienced with this occasion of use. Toxicosurveillance of ED presentations with analytical confirmation of drugs is crucial in identifying emerging drugs in the community and informing harm reduction strategies.
Iranian Men’s Sexual Life Issues After Their Wives’ Burn: A Qualitative Content Analysis Study
Authors: Eslamialiabadi Hassan , Nasiri Ahmad , Mahmoudirad Gholamhosein
Published: August 2022

Physical and psychological complications of burn injuries reduce the victims’ sexual quality of life and challenge their partners’ sexual satisfaction. There is no information about men’s sexual issues and behaviors. Previous studies did not address the impact of women’s burns on their husbands’ sexual lives. Therefore, this qualitative study aimed to characterize the sexual experiences of Iranian men after their wives’ burns. The study was performed on 16 men with surviving spouses of major burn using criterion-based purposive sampling. Semistructured interviews were analyzed using a qualitative content analysis approach. The results showed men’s sexual issues with three main themes and eight subthemes: 1) sexual desire restrictors (annoying scars, imposing roles, and wives’ sexual coldness), 2) degradation of marital sex (reduced frequency of sexual intercourses, temptation of extramarital affairs), and 3) effort to maintain sex (sexual self-sacrifice, sexual pretending, sexual precautions). According to men’s experiences, female sexual coldness, temptation for extramarital affairs, and sexual pretense were related to couples’ poor knowledge of sexual discourse. Thus, health professionals can use context-oriented educational program to promote the couples’ sexual knowledge and health after burns.
Dynamics of nitration during dark-induced leaf senescence in Arabidopsis reveals proteins modified by tryptophan nitration
Authors: Arasimowicz-Jelonek Magdalena , Jagodzik Przemysław , Płóciennik Artur , Sobieszczuk-Nowicka Ewa , Mattoo Autar , Polcyn Władysław , Floryszak-Wieczorek Jolanta
Published: August 2022

Nitric oxide (NO) is a critical molecule that links plant development with stress responses. Herein, new insights into the role of NO metabolism during leaf senescence in Arabidopsis are presented. A gradual decrease in NO emission accompanied dark-induced leaf senescence (DILS), and a transient wave of peroxynitrite (ONOO–) formation was detected by day 3 of DILS. The boosted ONOO– did not promote tryptophan (Trp) nitration, while the pool of 6-nitroTrp-containing proteins was depleted as senescence progressed. Immunoprecipitation combined with mass spectrometry was used to identify 63 and 4 characteristic 6-nitroTrp-containing proteins in control and individually darkened leaves, respectively. The potential in vivo targets of Trp nitration were mainly related to protein biosynthesis and carbohydrate metabolism. In contrast, nitration of tyrosine-containing proteins was intensified 2-fold on day 3 of DILS. Also, nitrative modification of RNA and DNA increased significantly on days 3 and 7 of DILS, respectively. Taken together, ONOO– can be considered a novel pro-senescence regulator that fine-tunes the redox environment for selective bio-target nitration. Thus, DILS-triggered nitrative changes at RNA and protein levels promote developmental shifts during the plant’s lifespan and temporal adjustment in plant metabolism under suboptimal environmental conditions.
Galaxy And Mass Assembly (GAMA): bulge-disc decomposition of KiDS data in the nearby Universe
Authors: Casura Sarah , Liske Jochen , Robotham Aaron S G , Brough Sarah , Driver Simon P , Graham Alister W , Häußler Boris , Holwerda Benne W , Hopkins Andrew M , Kelvin Lee S , Moffett Amanda J , Taranu Dan S , Taylor Edward N
Published: August 2022

We derive single Sérsic fits and bulge-disc decompositions for 13 096 galaxies at redshifts z < 0.08 in the GAMA II equatorial survey regions in the Kilo-Degree Survey (KiDS) g, r, and i bands. The surface brightness fitting is performed using the Bayesian two-dimensional profile fitting code ProFit. We fit three models to each galaxy in each band independently with a fully automated Markov chain Monte Carlo analysis: a single Sérsic model, a Sérsic plus exponential and a point source plus exponential. After fitting the galaxies, we perform model selection and flag galaxies for which none of our models are appropriate (mainly mergers/Irregular galaxies). The fit quality is assessed by visual inspections, comparison to previous works, comparison of independent fits of galaxies in the overlap regions between KiDS tiles and bespoke simulations. The latter two are also used for a detailed investigation of systematic error sources. We find that our fit results are robust across various galaxy types and image qualities with minimal biases. Errors given by the MCMC underestimate the true errors typically by factors 2–3. Automated model selection criteria are accurate to $\gt 90{{\ \rm per\ cent}}$ as calibrated by visual inspection of a subsample of galaxies. We also present g−r component colours and the corresponding colour–magnitude diagram, consistent with previous works despite our increased fit flexibility. Such reliable structural parameters for the components of a diverse sample of galaxies across multiple bands will be integral to various studies of galaxy properties and evolution. All results are integrated into the GAMA database.
B-Cell depletion therapy in IgG4-related disease: State of the art and future perspectives
Authors: Lanzillotta Marco , Stone John H , Della-Torre Emanuel
Published: August 2022

IgG4-related disease (IgG4-RD) is an increasingly recognized immune-mediated fibroinflammatory disorder that promptly responds to glucocorticoids but commonly relapses during steroid tapering or after discontinuation. In the last few years, B-cell depletion therapy with rituximab (RTX) proved to be effective in the induction of remission and maintenance treatment of IgG4-RD, providing a new powerful tool in the management of this emerging condition. In this review, we outline the pathogenetic rationale for using B-cell depleting agents in IgG4-RD, we summarize available clinical experience with RTX in this disease, and we describe future possible therapies targeting B-lymphocytes that are now in the pipeline.
A multi-institutional phase II trial of bevacizumab for recurrent and refractory meningioma
Authors: Kumthekar Priya , Grimm Sean Aaron , Aleman Roxanne T , Chamberlain Marc C , Schiff David , Wen Patrick Y , Iwamoto Fabio Massaiti , Gursel Demirkan Besim , Reardon David A , Purow Benjamin , Kocherginski Masha , Helenowski Irene , Raizer Jeffrey J
Published: August 2022

Background

Systemic therapies for refractory meningiomas are limited with no FDA-approved therapeutics. Vascular endothelial growth factor (VEGF) is a signaling protein associated with neovascularization, peritumoral edema, and meningioma tumorigenesis.

Methods

This phase II study investigates the efficacy of bevacizumab (BEV), a VEGF binding monoclonal antibody, in patients with progressive Grade I (G1M), Grade II (G2M), Grade III (G3M) meningioma, and other non-parenchymal tumors including vestibular schwannoma (n = 4) and hemangiopericytoma (n = 4) with the primary endpoint of progression-free survival rate at 6-months (PFS-6). Non-meningiomas were included with the respective meningioma grade in the analysis. Secondary endpoints include median overall survival (mOS) and response rate.

Results

Fifty Patients (26 women; median age 54 years; range 23–81), 42 with progressive meningioma were treated: 10 G1M, 20 G2M, and 12 G3M. Prior treatments include surgical resection (41 patients), radiosurgery (24 patients), external beam radiotherapy (28 patients), and chemotherapy (14 patients). Median infusions administered were 16 (range, 2–68). Response was graded using the Macdonald’s criteria. PFS-6, median PFS, and mOS were 87%, 22 months, 35 months for G1M; 77%, 23 months, 41 months for G2M; and 46%, 8 months, 12 months for G3M. Best radiographic responses include stable disease (G1M: 100%; G2M: 85%; G3M: 82%); partial response (G1M: 0%; G2M: 5%; G3M: 0%) and progressive disease (G1M: 0%; G2M: 10%; G3M:18%). The most common toxicities were hypertension (n = 19, 42.2%), proteinuria (n = 16, 35.6%), and fatigue (n = 14, 31.1%).

Conclusion

This study showed BEV is well tolerated and appears to be a promising systemic treatment option for patients with recurrent and refractory meningiomas.
The abscopal effect: systematic review in patients with brain and spine metastases
Authors: Pangal Dhiraj J , Yarovinsky Benjamin , Cardinal Tyler , Cote David J , Ruzevick Jacob , Attenello Frank J , Chang Eric L , Ye Jason , Neman Josh , Chow Frances , Zada Gabriel
Published: August 2022

Background

The abscopal effect is a rare phenomenon whereby local radiation induces a proposed immune-mediated anti-tumor effect at distant sites. Given the growing use of immunotherapies and systemic immune checkpoint inhibitors in neuro-oncologic practice, we aimed to review prior studies pertaining to this phenomenon in the context of tumor shrinkage both within the central nervous system as well as distant disease sites.

Methods

A systematic review in accordance with the PRISMA guidelines was conducted to identify all studies which assessed the abscopal effect in patients with treated metastatic cancer to the brain and/or spine. Articles were included if they reported the abscopal effect in patients (case studies) or if the abscopal effect was explicitly analyzed in case series with cohorts of patients with metastatic brain or spine tumors. Laboratory investigations and clinical trials investigating new therapies were excluded.

Results

Twenty reports met inclusion criteria [16 case reports, 4 case series (n = 160), total n = 174]. Case reports of the abscopal effect were in relation to the following cancers: melanoma (6 patients), breast cancer (3), lung adenocarcinoma (2), non-small-cell lung cancer (2), hepatocellular carcinoma (1), and renal cell carcinoma (1). Eleven patients had irradiation to the brain and 2 to the spine. Patients undergoing whole brain radiotherapy (6) had an average dose of 33.6 Gy over 8–15 fractions, and those undergoing stereotactic radiosurgery (5) had an average dose of 21.5 Gy over 1–5 fractions. One patient had radiation to the body and an intracranial abscopal effect was observed. Most common sites of extracranial tumor reduction were lung and lymph nodes. Ten case studies (57%) showed complete resolution of extra-CNS tumor burden. Median progression-free survival was 13 months following radiation. Four papers investigated incidence of abscopal effects in patients with metastatic melanoma to the brain who received immune checkpoint inhibitor therapy (n = 160); two papers found an abscopal effect in 35% and 52% of patients (n = 16, 21 respectively), and two papers found no evidence of abscopal effects (n = 61, 62).

Conclusions

Abscopal effects can occur following radiotherapy in patients with brain or spine metastases and is thought to be a result of increased anti-tumor immunity. The potential for immune checkpoint inhibitor therapy to be used in combination with radiotherapy to induce an abscopal effect is an area of active investigation.
An investigation of the conformity, feasibility, and expected clinical benefits of multiparametric MRI-guided dose painting radiotherapy in glioblastoma
Authors: Brighi Caterina , Keall Paul J , Holloway Lois C , Walker Amy , Whelan Brendan , de Witt Hamer Philip C , Verburg Niels , Aly Farhannah , Chen Cathy , Koh Eng-Siew , Waddington David E J
Published: August 2022

Background

New technologies developed to improve survival outcomes for glioblastoma (GBM) continue to have limited success. Recently, image-guided dose painting (DP) radiotherapy has emerged as a promising strategy to increase local control rates. In this study, we evaluate the practical application of a multiparametric MRI model of glioma infiltration for DP radiotherapy in GBM by measuring its conformity, feasibility, and expected clinical benefits against standard of care treatment.

Methods

Maps of tumor probability were generated from perfusion/diffusion MRI data from 17 GBM patients via a previously developed model of GBM infiltration. Prescriptions for DP were linearly derived from tumor probability maps and used to develop dose optimized treatment plans. Conformity of DP plans to dose prescriptions was measured via a quality factor. Feasibility of DP plans was evaluated by dose metrics to target volumes and critical brain structures. Expected clinical benefit of DP plans was assessed by tumor control probability. The DP plans were compared to standard radiotherapy plans.

Results

The conformity of the DP plans was >90%. Compared to the standard plans, DP (1) did not affect dose delivered to organs at risk; (2) increased mean and maximum dose and improved minimum dose coverage for the target volumes; (3) reduced minimum dose within the radiotherapy treatment margins; (4) improved local tumor control probability within the target volumes for all patients.

Conclusions

A multiparametric MRI model of GBM infiltration can enable conformal, feasible, and potentially beneficial dose painting radiotherapy plans.
Restraining the escape of lattice oxygen enables superior cyclic performance towards high-voltage Ni-rich cathodes
Authors: Yu Haifeng , Zhu Huawei , Jiang Hongliang , Su Xiaozhi , Hu Yanjie , Jiang Hao , Li Chunzhong
Published: August 2022

Layered Ni-rich cathodes, operating at high voltage with superior cyclic performance, are required to develop future high-energy Li-ion batteries. However, the worst lattice oxygen escape at the high-voltage region easily causes structural instability, rapid capacity fading and safety issues upon cycling. Here, we report a dual-track strategy to fully restrain the escape of lattice oxygen from Ni-rich cathodes within 2.7–4.5 V by one-step Ta doping and CeO2 coating according to their different diffusion energy barriers. The doped Ta can alleviate the charge compensation of oxygen anions as a positive charge centre to reduce the lattice oxygen escape and induce the formation of elongated primary particles, significantly inhibiting microcrack generation and propagation. Additionally, the layer of CeO2 coating effectively captures the remaining escaped oxygen and then the captured oxygen feeds back into the lattice during subsequent discharge. The resultant Ni-rich cathode enables a capacity of 231.3 mAh g−1 with a high initial coulombic efficiency of 93.5%. A pouch-type full cell comprising this cathode and a graphite anode exhibits >1000 times life cycles at 1C in the 2.7–4.5 V range, with 90.9% capacity retention.
Anomalous displacement reaction for synthesizing above-room-temperature and air-stable vdW ferromagnet PtTe2Ge1/3
Authors: Zhu Wenxuan , Song Cheng , Wang Qian , Bai Hua , Yin Siqi , Pan Feng
Published: August 2022

Emerging van der Waals (vdW) magnets provide a paradise for the exploration of magnetism in the ultimate two-dimensional (2D) limit, and the construction of integrated spintronic devices, and have become a research frontier in the field of low-dimensional materials. To date, prototypical vdW magnets based on metals of the first transition series (e.g. V, Cr, Mn and Fe) and chalcogen elements suffer from rapid oxidation restricted by the Hard-Soft-Acid-Base principle, as well as low Curie temperatures (TC), which has become a generally admitted challenge in 2D spintronics. Here, starting from air-unstable Cr2Ge2Te6 vdW thin flakes, we synthesize Ge-embedded PtTe2 (namely PtTe2Ge1/3) with superior air stability, through the displacement reaction in the Cr2Ge2Te6/Pt bilayer. In this process, the anomalous substitution of Cr with Pt in the thermal diffusion is inverse to the metal activity order, which can be attributed to the compatibility between soft-acid (Pt) and soft-base (Te) elements. Meanwhile, the layered uniform insertion of Ge unbalances Pt–Te bonds and introduces long-range ordered ferromagnetism with perpendicular magnetic anisotropy and a Curie temperature above room temperature. Our work demonstrates the anti-metal-activity-order reaction tendency unique in 2D transition-metal magnets and boosts progress towards practical 2D spintronics.
Flavored Tobacco Sales Restrictions and Teen E-cigarette Use: Quasi-experimental Evidence From California
Authors: Dove Melanie S , Gee Kevin , Tong Elisa K
Published: August 2022

Introduction

Flavored tobacco sales restrictions (FTSRs) are implemented to reduce access to flavored tobacco products. We examined the association between seven cities with local FTSRs implemented in 2018/2019 and e-cigarette use among high school students in the California Bay Area.

Aims and Methods

We analyzed data from the California Healthy Kids Survey using a difference-in-differences (D-I-D) strategy. We compared pre- and post-policy changes one year after implementation in current and ever e-cigarette use among students attending school in a city with a FTSR (exposed) (n = 20 832) versus without (unexposed) (n = 66 126). Other outcomes included ever marijuana use in an e-cigarette and ease of access to e-cigarettes.

Results

Pre- to post-policy, the adjusted odds of current and ever e-cigarette use did not significantly change among students exposed and unexposed to a FTSR. In the adjusted D-I-D analysis, the odds of current (aOR: 1.25, 95% CI: 0.95, 1.65) and ever e-cigarette use (aOR: 1.06, 95% CI: 0.89, 1.26) did not significantly change by exposure group. However, one year post-implementation, the odds of ease of access to e-cigarettes significantly increased among exposed (aOR: 1.57, 95% CI: 1.27, 1.95) and unexposed students (aOR: 1.54, 95% CI: 1.39, 1.70). Similarly, the odds of ever using marijuana in an e-cigarette significantly increased among exposed (aOR: 1.35, 95% CI: 1.19, 1.53) and unexposed students (aOR: 1.29, 95% CI: 1.20, 1.39).

Conclusions

Local FTSRs in the California Bay Area were not associated with a change in e-cigarette use one year post-implementation. Increased ease of access and marijuana use may be explanatory factors.

Implications

FTSRs were not associated with a decrease in current or ever e-cigarette use among high school students in the California Bay Area one-year post-implementation. Potential explanatory factors are that ease of access to e-cigarettes and using marijuana in an e-cigarette increased. More research is needed to understand the influence of these factors on youth access and behaviors. To address the youth e-cigarette epidemic, a comprehensive approach is needed, including policies, media campaigns, education programs, and cessation tools targeted to youth.
The START domain mediates Arabidopsis GLABRA2 dimerization and turnover independently of homeodomain DNA binding
Authors: Mukherjee Thiya , Subedi Bibek , Khosla Aashima , Begler Erika M , Stephens Preston M , Warner Adara L , Lerma-Reyes Ruben , Thompson Kyle A , Gunewardena Sumedha , Schrick Kathrin
Published: August 2022

Class IV homeodomain leucine-zipper transcription factors (HD-Zip IV TFs) are key regulators of epidermal differentiation that are characterized by a DNA-binding HD in conjunction with a lipid-binding domain termed steroidogenic acute regulatory-related lipid transfer (START). Previous work established that the START domain of GLABRA2 (GL2), a HD-Zip IV member from Arabidopsis (Arabidopsis thaliana), is required for TF activity. Here, we addressed the functions and possible interactions of START and the HD in DNA binding, dimerization, and protein turnover. Deletion analysis of the HD and missense mutations of a conserved lysine (K146) resulted in phenotypic defects in leaf trichomes, root hairs, and seed mucilage, similar to those observed for START domain mutants, despite nuclear localization of the respective proteins. In vitro and in vivo experiments demonstrated that while HD mutations impair binding to target DNA, the START domain is dispensable for DNA binding. Vice versa, protein interaction assays revealed impaired GL2 dimerization for multiple alleles of START mutants, but not HD mutants. Using in vivo cycloheximide chase experiments, we provided evidence for the role of START, but not HD, in maintaining protein stability. This work advances our mechanistic understanding of HD-Zip TFs as multidomain regulators of epidermal development in plants.
Gender and ethnicity bias in medicine: a text analysis of 1.8 million critical care records
Authors: Markowitz David M
Published: August 2022

Gender and ethnicity biases are pervasive across many societal domains including politics, employment, and medicine. Such biases will facilitate inequalities until they are revealed and mitigated at scale. To this end, over 1.8 million caregiver notes (502 million words) from a large US hospital were evaluated with natural language processing techniques in search of gender and ethnicity bias indicators. Consistent with nonlinguistic evidence of bias in medicine, physicians focused more on the emotions of women compared to men and focused more on the scientific and bodily diagnoses of men compared to women. Content patterns were relatively consistent across genders. Physicians also attended to fewer emotions for Black/African and Asian patients compared to White patients, and physicians demonstrated the greatest need to work through diagnoses for Black/African women compared to other patients. Content disparities were clearer across ethnicities, as physicians focused less on the pain of Black/African and Asian patients compared to White patients in their critical care notes. This research provides evidence of gender and ethnicity biases in medicine as communicated by physicians in the field and requires the critical examination of institutions that perpetuate bias in social systems.
Metformin attenuates osteoarthritis by targeting chondrocytes, synovial macrophages and adipocytes
Authors: Li Delong , Ruan Guangfeng , Zhang Yan , Zhao Yang , Zhu Zhaohua , Ou Qianhua , Huang Hong , Chen Jieli , Han Weiyu , Tang Su’an , Li Jia , Wang Liang , Chen Tianyu , Bai Xiaochun , Cai Daozhang , Ding Changhai
Published: August 2022

Objective

To investigate the therapeutic effect and mechanism of metformin on knee OA in normal diet (ND) mice or high-fat diet (HFD)-induced obese mice.

Methods

Destabilization of the medial meniscus surgery was performed in ND mice or HFD mice, and metformin was administrated in drinking water or not. The changes of OA joint structure, infiltration and polarization of synovial macrophages and circulating and local levels of leptin and adiponectin were evaluated. In vitro, the effects of metformin on chondrocytes and macrophages, and of conditioned mediums derived from mouse abdominal fat on murine chondrogenic cell line ATDC5 and murine macrophage cell line RAW264.7, were detected.

Results

Metformin showed protective effects on OA, characterized by reductions on OARSI score [2.00, 95% CI (1.15, 2.86) for ND mice and 3.17, 95% CI (2.37, 3.96) for HFD mice] and synovitis score [1.17, 95% CI (0.27, 2.06) for ND mice and 2.50, 95% CI (1.49, 3.51) for HFD mice] after 10 weeks of treatment, and the effects were more significant in HFD mice than in ND mice. Mechanistically, in addition to decreasing apoptosis and matrix-degrading enzymes expression in chondrocytes as well as infiltration and pro-inflammatory differentiation of synovial macrophages, metformin reduced leptin secretion by adipose tissue in HFD mice.

Conclusions

Metformin protects against knee OA which could be through reducing apoptosis and catabolism of chondrocytes, and suppressing infiltration and pro-inflammatory polarization of synovial macrophages. For obese mice, metformin has a greater protective effect in knee OA additionally through reducing leptin secretion from adipose tissue.
Survival in Swedish patients with systemic sclerosis: a nationwide population-based matched cohort study
Authors: Bairkdar Majd , Chen Enoch Yi-Tung , Dickman Paul W , Hesselstrand Roger , Westerlind Helga , Holmqvist Marie
Published: August 2022

Objectives

To conduct the first-ever nationwide, population-based cohort study investigating survival patterns of all patients with incident SSc in Sweden compared with matched individuals from the Swedish general population.

Methods

We used the National Patient Register to identify patients with incident SSc diagnosed between 2004 and 2015 and the Total Population Register to identify comparators (1:5), matched on sex, birth year and residential area. We followed them until death, emigration or the end of 2016. Follow-up of the general population comparators started the same date as their matched patients were included. We estimated all-cause survival using the Kaplan–Meier method, crude mortality rates and hazard ratios (HRs) using flexible parametric models.

Results

We identified 1139 incident patients with SSc and 5613 matched comparators. The median follow-up was 5.0 years in patients with SSc and 6.0 years for their comparators. During follow-up, 268 deaths occurred in patients with SSc and 554 in their comparators. The 5-year survival was 79.8% and the 10-year survival was 67.7% among patients with SSc vs 92.9% and 84.8%, respectively, for the comparators (P < 0.0001). The mortality rate in patients with SSc was 42.1 per 1000 person-years and 15.8 per 1000 person-years in their comparators, corresponding to an HR of 3.7 (95% CI 2.9, 4.7) at the end of the first year of follow-up and 2.0 (95% CI 1.4, 2.8) at the end of the follow-up period.

Conclusion

Despite advances in understanding the disease and in diagnostic methods over the past decades, survival is still severely impacted in Swedish patients diagnosed with SSc between 2004 and 2015.
Metabolite Signature and Differential Expression of Genes in Washington Navel Oranges (Citrus sinensis) Infected bySpiroplasma citri
Authors: McNeil Christopher J. , Araujo Karla , Godfrey Kristine , Slupsky Carolyn M.
Published: August 2022

Spiroplasma citri is the pathogen that causes citrus stubborn disease (CSD). Infection of citrus with S. citri has been shown to cause leaf mottling, reduce fruit yield, and stunt tree growth. Fruit from trees exhibiting symptoms of CSD are misshapen and discolored. The symptoms of CSD are easily confused with nutrient deficiencies or symptoms of citrus greening disease. In this study, young Washington navel oranges ( Citrus sinensis) were graft-inoculated with budwood originating from trees confirmed to be infected with S. citri. Leaf samples were collected monthly for 10 months for metabolomics and differential gene expression analyses. Significant differences in the concentration of metabolites and expressed genes were observed between control and S. citri-infected trees throughout the experiment. Metabolites and genes associated with important defense and stress pathways, including jasmonic acid signaling, cell wall modification, amino acid biosynthesis, and the production of antioxidant and antimicrobial secondary metabolites, were impacted by S. citri throughout the study, and even prior to symptom development. This work fills a current gap in knowledge surrounding the pathogenicity of S. citri and provides an updated mechanistic explanation for the development of CSD symptoms in S. citri-infected plants.
Addressing Health Inequities
Authors: Kennedy Lauren E. , Strayer Thomas E. , Balis Laura E.
Published: August 2022

Land grant universities are a key provider of community-based health promotion programs through the Cooperative Extension Service. However, Extension's current approach to addressing systemic social determinants of health is incomplete and inconsistent. The purpose of this study was to explore Extension health educators' perceptions of demand for health promotion programming targeting audiences most likely to experience health inequities. Health educators within 2 state Extension systems were invited to complete an online survey based on a capacity building model. Survey questions included rating perceptions of demand for programming for health disparate populations: low-income; Black and African American; Hispanic, Latino/a, Latinx; persons with disabilities; immigrants and refugees; and lesbian, gay, bisexual, and transgender. Analysis of variance and Bonferroni post hoc testing was used to determine differences in perceived demand between populations. Ninety-six educators completed the survey. Perceived demand for low-income population programming was significantly higher than for other populations. Perceived programming demand for immigrants and refugees and lesbian, gay, bisexual, and transgender people was significantly lower than for other populations. Individual and organizational-level factors, including racism and Extension's historical scope, likely contribute to the results. Engaging historically excluded Extension audiences requires time and resources to improve the Extension system and educator capacity for relationship building, trust building, and communication.
Maximum home blood pressure and cardiovascular outcomes in patients with type 2 diabetes: KAMOGAWA-HBP study
Authors: Hata Shinnosuke , Ushigome Emi , Yoshimura Takashi , Takegami Maya , Kitagawa Nobuko , Tanaka Toru , Hasegawa Goji , Ohnishi Masayoshi , Tsunoda Sei , Yokota Isao , Ushigome Hidetaka , Asano Mai , Hamaguchi Masahide , Yamazaki Masahiro , Fukui Michiaki
Published: August 2022

Objective:

The maximum blood pressure was reported as a possible marker of organ damage. We previously showed that maximum home blood pressure was significantly associated with development of diabetic nephropathy. In the same cohort of patients with diabetes as in the previous study, this study aimed to evaluate the prognostic blood pressure values for the onset of first cardiovascular events.

Methods:

This retrospective cohort study included 1082 patients with type 2 diabetes (47.0% female, median age 65.0) without a history of macrovascular complications. Blood pressure measurements were performed in triplicates every morning and evening for 14 consecutive days from the start of the study. Cox hazards model was used to evaluate the risk of primary endpoint, which was defined as the onset of first major cardiovascular event.

Results:

The primary endpoint occurred in 119 patients (incidence rate, 15.7/1000 person-years) during an average of 7.0-year follow-up. The adjusted hazard ratios (95% confidence interval [CI]) of maximum morning systolic blood pressure (SBP) and maximum evening SBP for cardiovascular events were 1.12 (1.01–1.24) and 1.19 (1.07–1.31), respectively, adjusted by sex, duration of diabetes, body mass index, hemoglobin A1c, low density lipoprotein cholesterol, smoking status, and use of antihypertensive medications. The cutoff values of maximum blood pressure for the events were 150 mmHg in the morning (hazard ratio, 1.73; 95% CI, 1.07–2.81) and 157 mmHg in the evening (hazard ratio, 2.30; 95% CI, 1.46–3.61), using the Youden's index.

Conclusion:

Maximum home blood pressure is a predictor of subsequent cardiovascular events in patients with type 2 diabetes.
PERIVASCULAR FLOWER-BUD-LIKE LESIONS ON EN FACE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN PATIENTS WITH VITREORETINAL LYMPHOMA
Authors: Chen Wenwen , Gu Junxiang , Liu Shixue , Zhao Zhenyang , Jiang Tingting , Xu Gezhi , Chang Qing
Published: August 2022

Purpose:

To describe perivascular flower-bud-like lesions (PFBLs) as novel characteristics of vitreoretinal lymphoma on en face optical coherence tomography (OCT) angiography.

Methods:

A retrospective chart review was performed on 23 consecutive patients (35 eyes), who had biopsy-proven vitreoretinal lymphoma between January 2018 and March 2021. En face OCT angiography images were analyzed before and after intervention. PFBLs were initially identified on midretinal slabs of en face OCT angiography, and were further characterized by other imaging modalities.

Results:

Perivascular flower-bud-like lesions were detected in 12 eyes (34.3%) of 8 patients, of which 8 eyes had best-corrected visual acuity of 20/40 or better. In 10 of the 12 eyes, PFBLs were detected within 6 months of symptom onset. On en face OCT angiography, PFBLs presented as punctate points or confluent bands surrounding retinal vessels, with arterial and venous involvement. In 4 of the 12 eyes, arteries were mainly affected. On OCT B-scans, PFBLs commonly appeared as hyperreflective full-thickness intraretinal lesions that colocalized with subretinal pigment epithelium deposits (3 eyes, 25%) and retinal pigment epithelium irregularities (4 eyes, 33.3%). However, PFBLs could not always be identified on other imaging modalities such as fundus photographs and fundus fluorescein angiography. In all eyes with follow-up, PFBLs attenuated or resolved months after receiving chemotherapy or diagnostic vitrectomy.

Conclusion:

PFBLs are characteristic imaging findings of vitreoretinal lymphoma and may facilitate an early diagnosis of vitreoretinal lymphoma, which would in turn lead to more timely and effective treatment.
Cute Cats, Disastrous Nightmare
Authors: Khor Hui Gim , Lott Penny Pooi Wah , Wan Ab Kadir Azida Juana , Ng Wei Loon
Published: August 2022

We reported a rare case of neuroretinitis secondary to cat scratch disease, which was successfully treated with steroids and antibiotic. A healthy young lady presented with a 6-day history of central blurring of vision over her right eye (OD) after an episode of flu. Visual acuity over the OD was 6/60 with positive relative afferent pupillary defect. There were no features of anterior uveitis. Fundus of the OD showed swollen, hyperemic optic disc with disc hemorrhages and early macular star but clear vitreous, with the absence of retinochoroiditis or vasculitic changes. The serum Bartonella henselae immunoglobulins M and G were raised. Magnetic resonance imaging of the brain and orbit showed a normal result. Our impression was neuroretinitis secondary to cat scratch disease. Her OD’s vision improved to 6/9 after completing a course of doxycycline and systemic corticosteroids. Early commencement of antibiotic and corticosteroids is essential to impede potentially blinding ocular complications despite its rarity.
Disseminated Nocardia veterana and Aspergillus fumigatus Coinfection and Review of the Literature of N. veterana Bacteremia
Authors: Kazanji Noora , Khaleel Ibrahim , Patel Payal K.
Published: August 2022

Nocardia veterana is a newly described species, of which rare cases of bloodstream infection have been reported. We describe the first case of disseminated nocardiosis with bacteremia caused by N. veterana with a concomitant disseminated aspergillosis presenting as Aspergillus fumigatus endophthalmitis. We discuss a literature review of all published cases of N. veterana bacteremia. This case highlights the challenge in diagnosing nocardiosis due to its inherent ability to mimic malignancy, other opportunistic infections, or pulmonary alveolar disease, as was seen in our case.
Integrated analysis of lncRNA-associated ceRNA network in p16-positive and p16-negative head and neck squamous cell carcinoma
Authors: Yang Yifan , Feng Ling , Wang Ru , Ma Hongzhi , He Shizhi , Fang Jugao
Published: August 2022

Determination of human papillomavirus (HPV) status has become clinically relevant for head and neck squamous cell carcinoma (HNSCC) patients. p16 immunohistochemistry is one of the recommended methods for classifying HPV status. However, long noncoding RNAs (lncRNAs) and related competing endogenous RNA (ceRNA) networks linked to different p16-status HNSCC are still absent.

In the present study, The Cancer Genome Atlas database provided RNA profiles as well as clinical information from 26 p16-positive HNSCC samples, 71 p16-negative HNSCC samples, and 44 adjacent normal control samples. Differentially expressed RNAs (DERNAs) between HNSCC samples and normal samples were identified by limma package in R. Functional enrichment analysis of differentially expressed mRNAs was performed using Clusterprofiler package in R. Survival analysis of DERNAs was carried out by survival package in R. The ceRNA network was constructed using GDCRNATools package in R.

A total of 102 lncRNAs, 196 microRNAs (miRNAs), and 2282 mRNAs were identified as p16-positive-specific DERNAs. There were 90 lncRNAs, 153 miRNAs, and 2038 mRNAs were identified as p16-negative-specific DERNAs. Functional enrichment analysis revealed that the differentially expressed mRNAs in the p16-positive and the p16-negative group were mainly enriched in the “DNA replication” and “extracellular matrix -receptor interaction” pathway, respectively. Among the top 25 DERNAs, there were 1 key lncRNA, 1 key miRNA, and 1 key messenger RNA in the p16-positive group and 2 key lncRNAs, 1 key miRNA, and 2 key mRNAs in the p16-negative group were significantly related to the overall survival. Then the ceRNA network in the p16-positive and p16-negative group was constructed. There were 5 lncRNAs, 16 miRNAs, and 66 mRNAs included in the p16-positive group ceRNA network and 1 lncRNA, 4 miRNAs, and 28 mRNAs included in the p16-negative group ceRNA network. Among the RNAs in the ceRNA network, 5 mRNAs were significantly related to the overall survival.

Taken together, we revealed the differential RNA expression profiling and the differential ceRNA network in the p16-positive and p16-negative group of HNSCC. Our findings provided a novel insight into this HPV-related cancer and potential biomarkers and therapeutic targets for HNSCC based on p16 status.
Changes in cesarean section rate before and after the end of the Korean Value Incentive Program
Authors: Park YouHyun , Kim Jae-hyun , Lee Kwang-soo
Published: August 2022

Background:

The Korean government implemented a value incentive program providing incentives to providers based on C-section rates, with the rates being publicized. The program ended in 2014 after the administration decided that the effects of the incentive program were limited. In this report, we analyzed changes in C-section rates with the value incentive program.

Methods:

The analysis used claim data from Korea’s National Health Insurance. The study period (2011–2016) was divided into two phases: before and after the program. This study included 95 providers that were tertiary or general hospitals having more than 200 deliveries per year during the study period. The dependent variable was the risk-adjusted C-section rate. Independent variables included time and hospital characteristics such as hospital type, district, and ownership. Interrupted time series analysis was performed to analyze the data.

Results:

Our results showed that risk-adjusted C-section rates increased immediately after the end of the incentive program for C-sections. The immediate effect of intervention, a change of 1.73% (P < .05), was statistically significant, as was the trend after intervention, at 0.21% (P < .0001). The slope showed an increase after the intervention to 0.25% per medical institution, which was contrary to the trend of the preintervention decline (negative slope).

Conclusion:

Risk-adjusted C-section rates increased immediately after the discontinuation of a value incentive program. Tertiary hospitals showed greater increases in C-section rates than general hospitals after the intervention.
Predictive value of ST-segment deviation in aVR in patients suffering from acute coronary syndrome: A retrospective cohort study
Authors: Hong Ji-Ge , Zeng Zhi-Yu
Published: August 2022

Changes in the ST-segment in aVR of electrocardiogram have been used to predict the morbidity of left main and/or 3-vessel disease (LM/3-VD) in patients with acute coronary syndrome (ACS). However, the association with patient prognosis has rarely been reported.

A total of 274 patients diagnosed with ACS were retrospectively evaluated following allocation into 1 of 3 groups: the ST-segment elevation (STE) group ≥ 0.05 mV, ST-segment depression (STD) group ≥ 0.05 mV, and the Isoelectric group in aVR. A comparison of clinical characteristics, coronary angiography results, major adverse cardiovascular events (MACE), and GRACE risk score was made.

Patients in the STE and STD groups were older and had a lower LVEF, a greater number of MACE and higher GRACE risk score, compared with patients in the isoelectric group. Patients in the STE group had significantly greater morbidity due to LM/3-VD than did the non-STE groups. In addition, as the amplitude of STE in aVR increased, the number of MACE, GRACE risk score, and the incidence of LM/3-VD increased. Furthermore, after adjusting for other clinical factors, multivariate statistical results indicated that STE ≥ 0.05 mV in aVR was the only predictor of LM/3-VD, whereas STD ≥ 0.05 mV was not. It was found that STE or STD ≥ 0.05 mV in aVR was an independent predictor of MACE.

STE ≥ 0.05 mV in aVR is associated with LM/3-VD. Furthermore, ST-segment deviation in aVR may have prognostic value of MACE and associated with higher GRACE risk scores in patients with ACS.
Effect of platelet-rich plasma on meniscus repair surgery: A meta-analysis of randomized controlled trials
Authors: Xie Yu-lei , Jiang Hong , Wang Shan , Hu An-li , Yang Zheng-lei , Mou Zhao , Wang Yinxu , Wu Qing
Published: August 2022

Background:

Studies have shown that platelet-rich plasma (PRP) can enhance the effect of meniscus repair, but some studies have suggested different views on the role of PRP. Therefore, a meta-analysis was conducted to determine whether PRP can enhance the effect of meniscus repair with respect to pain reduction and improved functionality and cure rate in patients with meniscus injury.

Methods:

PubMed, EMBASE, Cochrane Library Databases, clinicaltrials.gov, and the CNKI Database were searched from their inception till December 1, 2020. The RCTs reporting the outcomes of the Pain Visual Analog Scale (VAS), Lysholm score, healing rate, and adverse events were included. The risk of bias was assessed using Cochrane collaborative tools. The simulated results were expressed with effect size and 95% confidence interval, and sensitivity and subgroup analysis were performed.

Results:

The meta-analysis included 8 RCTs and 431 participants. Compared with the control group, use of PRP during meniscus surgery significantly improved the VAS (SMD: –0.40, P = .002, 95%CI: –0.66 to –0.15) and Lysholm score (MD: 3.06, P < .0001, 95%CI: 1.70–4.42) of meniscus injury, but the PRP showed no benefit in improving the healing rate of meniscus repair (RR: 1.22, P = .06, 95%CI: 0.99–1.51). No serious adverse events were reported in any study.

Conclusions:

PRP is safe and effective in improving the effect of meniscus repair as augment. High quality RCTs with long follow-up and definitive results are needed in the future to confirm the use and efficacy of PRP in meniscus tears.