bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating the relationship between extreme weather and cryptosporidiosis and giardiasis in Colorado: a multi-decade study using distributed-lag nonlinear models
Authors: Grover Elise N. , Crooks James L. , Carlton Elizabeth J. , Paull Sara H. , Allshouse William B. , Jervis Rachel H. , James Katherine A. 
Published: September 2023

AbstractEnvironmentally-mediated protozoan diseases like cryptosporidiosis and giardiasis are likely to be highly impacted by extreme weather, as climate-related conditions like temperature and precipitation have been linked to their survival, distribution, and overall transmission success. Our aim was to investigate the relationship between extreme temperature and precipitation and cryptosporidiosis and giardiasis infection using monthly weather data and case reports from Colorado counties over a twenty-one year period. Data on reportable diseases and weather among Colorado counties were collected using the Colorado Electronic Disease Reporting System (CEDRS) and the Daily Surface Weather and Climatological Summaries (Daymet) Version 3 dataset, respectively. We used a conditional Poisson distributed-lag nonlinear modeling approach to estimate the lagged association (between 0 and 12-months) between relative temperature and precipitation extremes and the risk of cryptosporidiosis and giardiasis infection in Colorado counties between 1997 – 2017, relative to the risk found at average values of temperature and precipitation for a given county and month. We found distinctly different patterns in the associations between temperature extremes and cryptosporidiosis, versus temperature extremes and giardiasis. When maximum or minimum temperatures were high (90thpercentile) or very high (95thpercentile), we found a significant increase in cryptosporidiosis risk, but a significant decrease in giardiasis risk, relative to risk at the county and calendar-month mean. Conversely, we found very similar relationships between precipitation extremes and both cryptosporidiosis and giardiasis, which highlighted the prominent role of long-term (>8 months) lags. Our study presents novel insights on the influence that extreme temperature and precipitation can have on parasitic disease transmission in real-world settings. Additionally, we present preliminary evidence that the standard lag periods that are typically used in epidemiological studies to assess the impacts of extreme weather on cryptosporidiosis and giardiasis may not be capturing the entire relevant period.
Extracellular Histones Promote Calcium Phosphate-Dependent Calcification in Mouse Vascular Smooth Muscle Cells
Authors: Hoshino Tomonori , Kharaghani Davood , Kohno Shohei 
Published: September 2023

SummaryVascular calcification, a major risk factor for cardiovascular events, is associated with a poor prognosis in chronic kidney disease (CKD) patients. This process is often associated with the transformation of vascular smooth muscle cells (VSMCs) into cells with osteoblast-like characteristics. Damage-associated molecular patterns (DAMPs), such as extracellular histones released from damaged or dying cells, are suspected to accumulate at calcification sites. To investigate the potential involvement of DAMPs in vascular calcification, we assessed the impact of externally added histones (extracellular histones) on calcium and inorganic phosphate-induced calcification in mouse VSMCs. Our study found that extracellular histones intensified calcification. We also observed that the histones decreased the expression of VSMC marker genes, while simultaneously increasing the expression of osteoblast marker genes. Additionally, histones treated with DNase I, which degrades dsDNA, attenuated this calcification, compared with the non-treated histones, suggesting a potential involvement of dsDNA in this process. Elevated levels of dsDNA were also detected in the serum of CKD model mice, underlining its potential role in vascular calcification in CKD. Our findings suggest that extracellular histones could play a pivotal role in the vascular calcification observed in CKD.Graphical abstract
Pre-existing tissue mechanical hypertension at adherens junctions disrupts apoptotic extrusion in epithelia
Authors: Mann Zoya , Lim Fayth , Verma Suzie , Nanavati Bageshri N. , Davies Julie M. , Begun Jakob , Hardeman Edna C. , Gunning Peter W. , Subramanyam Deepa , Yap Alpha S. , Duszyc Kinga 
Published: September 2023

AbstractApical extrusion is a tissue-intrinsic process that allows epithelia to eliminate unfit or surplus cells. This is exemplified by the early extrusion of apoptotic cells, which is critical to maintain the epithelial barrier and prevent inflammation. Apoptotic extrusion is an active mechanical process, which involves mechanotransduction between apoptotic cells and their neighbours, as well as local changes in tissue mechanics. Here we report that the pre-existing mechanical tension at adherens junctions conditions the efficacy of apoptotic extrusion. Specifically, increasing baseline mechanical tension by overexpression of a phosphomimetic Myosin II regulatory light chain (MRLC) compromises apoptotic extrusion. This occurs when tension is increased in either the apoptotic cell or its surrounding epithelium. Further, we find that the pro-inflammatory cytokine, TNFα, stimulates Myosin II and increases baseline AJ tension to disrupt apical extrusion, causing apoptotic cells to be retained in monolayers. Importantly, reversal of mechanical tension with an inhibitory MRLC mutant or tropomyosin inhibitors is sufficient to restore apoptotic extrusion in TNFα-treated monolayers. Together, these findings demonstrate that baseline levels of tissue tension are important determinants of apoptotic extrusion, which can potentially be co-opted by pathogenetic factors to disrupt the homeostatic response of epithelia to apoptosis.
Pathological mutations reveal the key role of the cytosolic iRhom2 N-terminus for phosphorylation-independent 14-3-3 interaction and ADAM17 binding, stability, and activity
Authors: Bläsius Katharina , Ludwig Lena , Knapp Sarah , Flaßhove Charlotte , Sonnabend Friederike , Keller Diandra , Tacken Nikola , Gao Xintong , Kahveci-Türköz Selcan , Grannemann Caroline , Babendreyer Aaron , Adrain Colin , Huth Sebastian , Baron Jens Malte , Ludwig Andreas , Düsterhöft Stefan 
Published: September 2023

AbstractThe protease ADAM17 plays an important role in inflammation and cancer and is regulated by iRhom2. Mutations in the cytosolic N-terminus of human iRhom2 cause tylosis with oesophageal cancer (TOC). In mice, partial deletion of the N-terminus results in a curly hair phenotype (cub). These pathological consequences are consistent with our findings that iRhom2 is highly expressed in keratinocytes and in oesophageal cancer. Cub and TOC are associated with hyperactivation of ADAM17-dependent EGFR signalling. However, the underlying molecular mechanisms are not understood. We have identified a non-canonical, phosphorylation-independent 14-3-3 interaction site that encompasses all known TOC mutations. Disruption of this site dysregulates ADAM17 activity. The larger cub deletion also includes the TOC site and thus also dysregulated ADAM17 activity. The cub deletion, but not the TOC mutation, also causes severe reductions in stimulated shedding, binding, and stability of ADAM17, demonstrating the presence of additional regulatory sites in the N-terminus of iRhom2. Overall, this study contrasts the TOC and cub mutations, illustrates their different molecular consequences, and reveals important key functions of the iRhom2 N-terminus in regulating ADAM17.
Preclinical screen for protection efficacy of chlamydial antigens that are immunogenic in humans
Authors: Lu Chunxue , Wang Jie , Zhong Guangming 
Published: September 2023

AbstractTo search for subunit vaccine candidates, immunogenic chlamydial antigens identified in humans were evaluated for protection against both infection and pathology in a mouse genital tract infection model under three different immunization regimens. The intramuscular immunization regimen was first used to evaluate 106 chlamydial antigens, which revealed that two antigens significantly reduced while 11 increased genital chlamydial burden. The two infection-reducing antigens failed to prevent pathology and 23 additional antigens even exacerbated pathology. Thus, intranasal mucosal immunization was tested next since intranasal inoculation with liveC. muridarumprevented both genital infection and pathology. Two of 29 chlamydial antigens evaluated were found to prevent genital infection but not pathology and three exacerbate pathology. To further improve protection efficacy, a combinational regimen (intranasal priming + intramuscular boosting + a 3rdintraperitoneal/subcutaneous boost) was tested. This regimen identified 4 infection-reducing antigens but only one of them prevented pathology. Unfortunately, this protective antigen was not advanced further due to its amino acid sequence homology with several human molecules. Two pathology-exacerbating antigens were also found. Nevertheless, intranasal mucosal priming with viableC. muridarumin control groups consistently prevented both genital infection and pathology regardless of the subsequent boosters. Thus, screening 140 different chlamydial antigens with 21 repeated multiple times in 17 independent experiments failed to identify a subunit vaccine candidate but the efforts have revealed pathogenic antigens and demonstrated the superiority of viable chlamydial organisms in inducing immunity against both genital infection and pathology, laying the foundation for developing an attenuated live Chlamydia vaccine.ImportanceThis manuscript describes a systematical effort in searching for a chlamydial subunit vaccine by taking advantage of both the immunogenic chlamydial antigens identified in humans and a robust mouse genital tract infection model for simultaneously evaluating protection against both genital infection and pathology. Screening 140 different chlamydial antigens (21 repeated multiple times) using three different immunization regimens in 17 independent experiments identified no subunit vaccine candidate. Nevertheless, the efforts revealed multiple pathogenic chlamydial antigens and demonstrated the superiority of mucosal inoculation with viable chlamydial organisms for inducing immunity against both genital infection and pathology, suggesting that a live attenuated Chlamydia vaccine strategy should be considered.
Cefiderocol is an effective topical monotherapy for experimental extensively-drug resistantPseudomonas aeruginosakeratitis
Authors: Romanowski Eric G. , Mumper Sonya M. , Shanks Hazel Q. , Yates Kathleen A. , Mandell Jonathan B. , Zegans Michael E. , Shanks Robert M. Q. 
Published: September 2023

ABSTRACTPurposeTo test cefiderocol, a siderophore-cephalosporin antibiotic for topical monotherapy treatment of experimental extensively drug resistant (XDR)Pseudomonas aeruginosakeratitis.DesignPreclinical study.Subjects and ControlsDeidentifiedP. aeruginosakeratitis isolates, XDRP. aeruginosafrom eye drop outbreak, rabbits, saline, cefiderocol 50 mg/ml, ciprofloxacin 0.3%, and tobramycin 14 mg/ml.Methods, Intervention, or TestingCefiderocol antibacterial activity againstP. aeruginosakeratitis isolates (n=135) was evaluated by minimum inhibitory concentration (MIC) testing. Ocular toxicity/tolerability and antibacterial efficacy were testedin vivowith experimental rabbit models. Corneal concentrations and stability were assessed using a bioassay.Main Outcome MeasuresMIC analysis for susceptibility, graded tests for ocular toxicity/tolerability, CFU analysis for bacterial burden, corneal cefiderocol concentrations.Results100% ofP. aeruginosakeratitis isolates were susceptible to cefiderocol (n=135), the MIC90was 0.125 µg/ml including the XDR isolate (MIC = 0.125 µg/ml). Topical cefiderocol 50 mg/ml was minimally toxic to the ocular surface and was well tolerated. For the XDRP. aeruginosaisolate, topical cefiderocol 50 mg/ml, significantly decreased corneal CFU compared to ciprofloxacin 0.3%, tobramycin 14 mg/ml, and saline. In addition, tobramycin 14 mg/ml was more effective than the saline control. Mean cefiderocol corneal concentrations were 191x greater than the MIC90of theP. aeruginosakeratitis isolates. Refrigerated cefiderocol maintained antimicrobial activity over a one-month period.ConclusionsThese results demonstrate that cefiderocol is well tolerated on rabbit corneas and is effective againstP. aeruginosakeratitis isolatesin vitroand was effectivein vivoagainst an XDR isolate in a rabbit keratitis model. Given the recent outbreak of keratitis caused by this XDRP. aeruginosa, cefiderocol is a promising additional antibiotic that should be further evaluated for topical treatment of keratitis caused by antibiotic resistantP. aeruginosa.
Tuberculosis and HIV/AIDS Co-infection in Patients Attending Directly Observed Treatment Short-Course (DOTS) Centers in Anambra State, Nigeria
Authors: Okeke Monique , Eze Peter M. , Chukwudebelu Adaeze E. , Nwankwo Chidiebere J. , Eze Nchekwube K. , Okafor Uchenna U. , Abonyi Isaiah C. , Okereke Eric E. , Obasi Kalu O. , Ede Okorie A. , Ejikeugwu Chika P. , Ilo Cajetan I. , Okafor Jerome O. 
Published: September 2023

ABSTRACTBackground and Aim(s)This study retrospectively assessed the prevalence of TB and HIV/AIDS co-infection among patients that attended the Directly Observed Treatment Short-course (DOTS) centers in Anambra State, Southeast, Nigeria, between 2013 and 2017.MethodsThe study adopted a descriptive and retrospective epidemiological survey design. A total of 1443 case files of patients aged 15 to 60 who were treated in DOTS centers selected from Anambra State’s 21 Local Government Areas between 2013 and 2017 were investigated. The uniform data form, a standardized instrument used in Anambra State’s health facilities for data collection, was used to collect data from case files of all those identified as co-infected with TB and HIV/AIDS.ResultsThe mean prevalence rate of TB and HIV/AIDS co-infection in the state during the five-year period (2013–2017) was 20%. The highest annual prevalence of TB and HIV/AIDS co-infection was recorded in 2014 (23.84%). The state’s prevalence of TB and HIV/AIDS co-infection increased dramatically from 13.17% in 2013 to 23.84% in 2014, followed by a slight downward trend to 22.80% in 2015, 20.17% in 2016, and 20.03% in 2017. In terms of gender, age, marital status, and occupation, females (59.5%), those aged 15 to 25 years (30.7%), married people (43.9%), and traders/business owners (50.7%), respectively, had the highest rates of tuberculosis and HIV/AIDS co-infection during the study period.ConclusionThe findings of this study show that young people, females, married people, and traders/business owners appear to be the most vulnerable groups affected by TB and HIV/AIDS co-infection, accounting for the majority of the disease burden in the state. To address the high prevalence of TB and HIV/AIDS co-infection in the Anambra State, novel intervention and control programs should be developed and implemented, and existing intervention frameworks should be strengthened.
Exploring factors for meaningful patient involvement in infectious disease clinical studies: A qualitative pilot study among key stakeholders
Authors: Moggré S. , ten Doesschate T. , Sieswerda E. , Romijnders K.A.G.J. 
Published: September 2023

AbstractIntroductionThe attitude towards patient involvement in clinical research has changed dramatically over the years, from research about patient to research with patients. This qualitative study aimed to explore perceptions, ideas, and opinions of stakeholders about integrating the patient perspective into clinical research in infectious diseases in the Netherlands.MethodsStakeholders involved with clinical research in infectious diseases were purposefully sampled between March and June 2023. Interviews were conducted using a semi-structured guide based on the Consolidated Framework for Intervention Research and feasibility framework.ResultsOf the thirteen stakeholders, six were (clinical) researchers, two represented pharmaceutical companies, two were involved with policy making, and three were patient representatives. Patient involvement in the design and conduct of clinical research in infectious diseases was seen as crucial, although the mode of involvement could differ between research in acute and chronic infections. Stakeholders observed a gap among patients and clinical researchers, which was believed to lead to a phenomenon described as an ivory tower. Key opinion leaders may potentially bridge these barriers and serve as protagonists for meaningful patient involvement. Stakeholders acknowledged the need of communication and expertise to integrate the patient perspective in clinical research in infectious diseases.ConclusionOur qualitative analysis underlines that despite barriers, such as communication and expertise, stakeholders recognize the importance of integrating the patient perspective in clinical research in infectious diseases to improve the quality, relevance, recruitment, and dissemination. Further research is needed to address distinctions between acute and chronic infectious diseases in terms of patient involvement.
Strong paracrine effects of SASP from senescence-induced severe early-onset COPD-derived fibroblasts
Authors: Meuleman R.A. , Timens W. , Kooistra W. , van den Berge M. , Brandsma C-A. , Woldhuis R.R. 
Published: September 2023

AbstractBackgroundLung fibroblasts from Severe Early-Onset (SEO-)COPD patients exhibit increased cellular senescence with higher levels of senescence-associated secretory phenotype (SASP) protein secretion. Yet, the impact of senescent fibroblasts, and their SASP, on surrounding fibroblasts in SEO-COPD lungs remains unclear.AimTo identify the effect of the SASP secreted by senescent SEO-COPD-derived fibroblasts on surrounding lung fibroblasts.MethodsCellular senescence was induced in lung fibroblasts derived from seven SEO-COPD patients (age≤53 years, FEV1<40% predicted), and conditioned medium (CM) containing the SASP, was collected (senescent CM). CM from untreated fibroblasts was used as control. Fibroblasts were stimulated with senescent and control CM, and with tissue plasminogen activator (t-PA), a previously identified COPD-associated SASP protein. Effects on paracrine senescence, inflammation, and extracellular matrix (ECM) regulation were assessed.ResultsStimulation with senescent CM increased the percentage of Senescence-associated beta-galactosidase positive fibroblasts and decreased p16, p21 &LMNB1expression (p<0.05). T-PA did not affect these markers. Senescent CM increased IL-8 gene expression, increased IL-6 secretion, and strongly increased IL-8 secretion compared to control CM. T-PA slightly decreased IL-6 and IL-8 secretion. Additionally, senescent CM and t-PA stimulation both reduced decorin secretion. Senescent CM reducedFN1gene expression, whileDCNandMMP2expression remained unaffected. T-PA did not affect ECM gene expression.ConclusionThe SASP from senescence-induced SEO-COPD-derived fibroblasts has a strong paracrine effect on untreated fibroblasts, suggesting that senescent lung fibroblasts contribute to chronic inflammation and ECM dysregulation. These findings imply involvement of senescent fibroblasts in abnormal lung ageing and possibly disease pathology in COPD.
JAZF1 is transcriptionally regulated by SOX11 and promotes cardiac fibrosis by PI3K-Akt pathway
Authors: Mo Yujing , Wang Rui , Liang Yingcong , Zhou Yingling , Zhang Ying , Xue Ling 
Published: September 2023

AbstractBackgroundCardiac fibrosis is a component of all chronic heart diseases. JAZF1 regulates metabolism through various mechanisms; however, its role in cardiac fibrosis remains unclear. We aimed to investigate the role of JAZF1 in cardiac fibrosis.MethodsA rat cardiac fibrosis model was established by administering isoproterenol subcutaneously for 14 days (5 mg/kg/day); an equal volume of saline was administered to the control group. Cardiac fibroblasts (CFs) were treated with TGF-β1 for 48 h to mimic cardiac fibrosis in vitro.ResultsJAZF1 expression at the protein and mRNA levels was enhanced in CFs and cardiac fibrosis tissues. JAZF1 downregulation suppressed CFs’ proliferation and migration. Western blotting showed that the PI3K/Akt signaling pathway was significantly decreased after JAZF1 knockdown. Further experiments revealed that SOX11 is an important transcription factor whose overexpression and downregulation enhanced and suppressed JAZF1 levels, respectively. Luciferase analysis showed that SOX11 interacted with the JAZF1 promoter. Moreover, SOX11 promoted cardiac fibrosis by regulating JAZF1 expression.ConclusionsJAZF1 was enhanced in cardiac fibrosis tissue and TGF-β-treated CFs. JAZF1 knockdown decreased CFs’ migration and proliferation, possibly remediated by SOX11 with activation of PI3k/Akt signaling pathways.
Brand engagement and community user behaviors in online interest communities: exploring a moderated mediation model
Authors: Hao Ruohong , Liang Xiaobei , Meng Hu 
Published: September 2023

PurposeAs fertile soil for product promotion, online interest communities have gradually come into brands' view. However, existing research does not clarify whether brand engagement in consumer interaction is beneficial to the development of online interest communities. This study attempts to investigate the effects of brand engagement on the online interest community operation.Design/methodology/approachThe authors propose a model that delineated the influence of brand engagement on consumers' citizenship behavior in the online interest community from the commitment-trust perspective. Scenario-based experiments were conducted and 536 data were collected by simple random sampling.FindingsResults shows that a stronger perception of brand engagement has a positive influence on the relationship (trust and commitment) between the community and its users, which further influences online community citizenship behavior (feedback, advocacy and tolerance) of both posters and lurkers, especially for the posters. Although relationships are more complex, brand engagement activates the development of online interest communities to some extent.Originality/valueThis original study contributes to the commitment-trust theory by examining the impact of brand engagement on citizenship behavior via community commitment and trust in the online interest community context. In addition, this study compares the moderating effect of posters vs lurkers on the relationship between brand engagement and citizenship behavior in the online interest community.