bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computational tibial bone remodeling over a population after total knee arthroplasty: A comparative study
Authors: Anijs Thomas , Eemers Sanne , Minoda Yukihide , Wolfson David , Verdonschot Nico , Janssen Dennis 
Published: October 2021

AbstractPeriprosthetic bone loss is an important factor in tibial implant failure mechanisms in total knee arthroplasty (TKA). The purpose of this study was to validate computational postoperative bone response using longitudinal clinical DEXA densities. Computational remodeling outcome over a population was obtained by incorporating the strain‐adaptive remodeling theory in finite element (FE) simulations of 26 different tibiae. Physiological loading conditions were applied, and bone mineral density (BMD) in three different regions of interest (ROIs) was considered over a postoperative time of 15 years. BMD outcome was compared directly to previously reported clinical BMD data of a comparable TKA cohort. Similar trends between computational and clinical bone remodeling over time were observed in the two proximal ROIs, with most rapid bone loss taking place in the initial months after TKA and BMD starting to level in the following years. The extent of absolute proximal BMD change was underestimated in the FE population compared with the clinical subject group, which might be the result of significantly higher initial clinical baseline BMD values. Large differences in remodeling response were found in the distal ROI, in which resorption was measured clinically, but a large BMD increase was predicted by the FE models. Multiple computational limitations, related to the FE mesh, loading conditions, and strain‐adaptive algorithm, likely contributed to the extensive local bone formation. Further research incorporating subject‐specific comparisons using follow‐up CT scans and more extensive physiological knee loading is recommended to optimize bone remodeling more distal to the tibial baseplate.
Current state of technologies and recognition of anti‐SSA/Ro antibodies in China: A multi‐center study
Authors: Chen Yu‐Lan , Hu Chao‐Jun , Peng Lin‐Yi , Wang Chu‐Han , Zhao Yan , Zhang Wen , Liu Dong‐Zhou ,   Chinese Sjögren's Syndrome Collaborative Research Group
Published: October 2021

AbstractBackgroundPrevious studies have demonstrated that Ro60 and Ro52 have different clinical implications, and anti‐Ro52 antibodies are an independent serum marker of systemic autoimmune diseases, including Sjögren's syndrome. Many different assays have been adopted to detect anti‐Sjögren's syndrome antigen A (SSA)/Ro antibodies, while to date no specific approach has been recommended as optimal for anti‐SSA/Ro antibody testing. Herein, we performed a multi‐center study to explore the current clinical utility of different strategies for anti‐SSA/Ro antibody testing in China.MethodsTwenty‐one tertiary care centers were included in this questionnaire‐based study. The self‐administered questionnaire mainly includes testing methods for anti‐SSA/Ro antibodies, reporting system of results, and interpretation of results by clinicians.ResultsSix different methods were applied to detect anti‐SSA/Ro antibodies in the 21 centers. Line immunoassay (eight different commercial kits) was the most frequently adopted method (21/21, 100%), with different cutoff values and strategies for intensity stratification. There were two reporting systems: One was reported as “anti‐SSA antibodies” and “anti‐Ro52 antibodies” (12/21, 57%), while the other was “anti‐SSA/Ro60 antibodies” and “anti‐SSA/Ro52 antibodies” (9/21, 43%). Notably, six centers (29%) considered either positive anti‐Ro60 or anti‐Ro52 antibodies as positive anti‐SSA antibodies, all of which adopted the latter reporting system.ConclusionSignificant variabilities existed among anti‐SSA/Ro assays. Nearly 30% of centers misinterpreted the definition of positive anti‐SSA antibodies, which may be attributed to the confusing reporting systems of line immunoassay. Therefore, we advocate standardization of the nomenclature of anti‐SSA/Ro antibodies, changing the “anti‐SSA/Ro52” label in favor of the “anti‐Ro52” antibodies for a clear designation.
Identification of dyslipidemia as a risk factor for sudden sensorineural hearing loss: A multicenter case‐control study
Authors: Li Xiaoqing , Chen Binghua , Zhou Xingxing , Ye Fan , Wang Yumin , Hu Wangqiang 
Published: October 2021

AbstractBackgroundRecently, several studies have reported an association between lipid profiles and sudden sensorineural hearing loss (SSNHL), yet there is considerable variability between the individual studies in defining the precise association between serum lipids levels and SSNHL. This study sought to identify a possible relationship between dyslipidemia and the prevalence and prognosis of SSNHL.MethodsA case‐control study was carried out at two independent medical centers, including 2,288 SSNHL patients and 2,288 healthy controls. Clinical characteristics and serum lipid parameters were assessed, including total cholesterol (CHOL), high‐density lipoprotein (HDL), low‐density lipoprotein (LDL), triglycerides (Trig), apolipoprotein AI (ApoAI), apolipoprotein B (ApoB), and lipoprotein a (Lpa). Multivariate logistic regression analysis was performed to assess the relationship between lipid profiles and SSNHL in the 4,576 subjects.ResultsSignificant differences were identified in several conventional serum lipid markers including CHOL, Trig, HDL, LDL, ApoAI, ApoB, and Lpa, between SSNHL patients and healthy controls. Serum ApoAI levels were significantly lower in patients with bilateral SSNHL compared to unilateral SSNHL. Binary logistic regression analysis revealed that higher levels of ApoB, LDL, Trig, and lower levels of ApoAI and HDL were all associated with an increased risk of SSNHL. After clinical characterization, multivariate analysis showed that only low levels of ApoB predicted likelihood of a recovery of more than 30 dB among patients with SSNHL.ConclusionsSerum lipids are associated with the incidence and prognosis of SSNHL. Identification of dyslipidemia may improve early evaluation and management of SSNHL risks.
Update on Cilostazol: A Critical Review of Its Antithrombotic and Cardiovascular Actions and Its Clinical Applications
Authors: Manolis Antonis A. , Manolis Theodora A. , Melita Helen , Mikhailidis Dimitri P. , Manolis Antonis S. 
Published: October 2021

AbstractCilostazol, a phosphodiesterase III inhibitor, has vasodilating and antiplatelet properties with a low rate of bleeding complications. It has been used over the past 25 years for improving intermittent claudication in patients with peripheral artery disease (PAD). Cilostazol also has demonstrated efficacy in patients undergoing percutaneous revascularization procedures for both PAD and coronary artery disease. In addition to its antithrombotic and vasodilating actions, cilostazol also inhibits vascular smooth muscle cell proliferation via phosphodiesterase III inhibition, thus mitigating restenosis. Accumulated evidence has shown that cilostazol, due to its “pleiotropic” effects, is a useful, albeit underutilized, agent for both coronary artery disease and PAD. It is also potentially useful after ischemic stroke and is an alternative in those who are allergic or intolerant to classical antithrombotic agents (eg, aspirin or clopidogrel). These issues are herein reviewed together with the pharmacology and pharmacodynamics of cilostazol. Large studies and meta‐analyses are presented and evaluated. Current guidelines are also discussed, and the spectrum of cilostazol's actions and therapeutic applications are illustrated.
Effects and tolerability of exercise therapy modality on cardiorespiratory fitness in lung cancer: a randomized controlled trial
Authors: Scott Jessica M. , Thomas Samantha M. , Herndon James E. , Douglas Pamela S. , Yu Anthony F. , Rusch Valerie , Huang James , Capaci Catherine , Harrison Jenna N. , Stoeckel Kurtis J. , Nilsen Tormod , Edvardsen Elisabeth , Michalski Meghan G. , Eves Neil D. , Jones Lee W. 
Published: October 2021

AbstractBackgroundPoor cardiorespiratory fitness (CRF) is a cardinal feature of post‐treatment primary lung cancer. The most effective exercise therapy regimen to improve CRF has not been determined.MethodsIn this parallel‐group factorial randomized controlled trial, lung cancer survivors with poor CRF (below age–sex sedentary values) were randomly allocated to receive 48 consecutive supervised sessions thrice weekly of (i) aerobic training (AT)—cycle ergometry at 55% to >95% of peak oxygen consumption (VO2peak); (ii) resistance training (RT)—lower and upper extremity exercises at 50–85% of maximal strength; (iii) combination training (CT)—AT plus RT; or (iv) stretching attention control (AC) for 16 weeks. The primary endpoint was change in CRF (VO2peak, mL O2·kg−1·min−1). Secondary endpoints were body composition, muscle strength, patient‐reported outcomes, tolerability (relative dose intensity of exercise), and safety. Analysis of covariance determined change in primary and secondary endpoints from baseline to post‐intervention (Week 17) with adjustment for baseline values of the endpoint and other relevant clinical covariates.ResultsNinety patients (65 ± 9 years; 66% female) were randomized (AT, n = 24; RT, n = 23; CT, n = 20; and AC, n = 23) of the planned n = 160. No serious adverse events were observed. For the overall cohort, the lost‐to‐follow‐up rate was 10%. Mean attendance was ≥75% in all groups. In intention‐to‐treat analysis, VO2peak increased 1.1 mL O2·kg−1·min−1 [95% confidence interval (CI): 0.0, 2.2, P = 0.04] and 1.4 mL O2·kg−1·min−1 (95% CI: 0.2, 2.5, P = 0.02) in AT and CT, respectively, compared with AC. There was no difference in VO2peak change between RT and AC (−0.1 mL O2·kg−1·min−1, 95% CI: −1.2, 1.0, P = 0.88). Favourable improvements in maximal strength and body composition were observed in RT and CT groups compared with AT and AC groups (Ps < 0.05). No between‐group changes were observed for any patient‐reported outcomes. Relative dose intensity of exercise was lower in RT and CT compared with AT (Ps < 0.05).ConclusionsIn the context of a smaller than planned sample size, AT and CT significantly improved VO2peak in lung cancer survivors; however, the tolerability‐to‐benefit ratio was superior for AT and hence may be the preferred modality to target impaired CRF in post‐treatment lung cancer survivors.
Strength of the genetic counselor: patient relationship is associated with extent of increased empowerment in patients with arrhythmogenic cardiomyopathy
Authors: Murray Brittney , Tichnell Crystal , Burch Ashley E. , Calkins Hugh , James Cynthia A. 
Published: October 2021

AbstractGenetic testing and genetic counseling (GC) are increasingly recommended in the cardiovascular setting, with multiple guidelines recommending GC for patients with or at risk for inherited cardiovascular conditions. There are scant data, however, describing patient outcomes to guide evidence‐based care. No studies have quantified the influence of the strength of the genetic counselor:patient relationship on outcomes. Individuals referred for first time GC at the Johns Hopkins Arrhythmogenic Cardiomyopathy (ACM) center were surveyed prior to their visit and immediately after, before any genetic test results ordered at the session had been returned. Outcomes and measures were selected based on the Reciprocal Engagement Model of GC and include empowerment assessed by the Genetic Counseling Outcome Scale (GCOS), anxiety assessed by the Cardiac Anxiety Questionnaire (CAQ), and genetic counselor:patient therapeutic alliance assessed by the Working Alliance Inventory (WAI‐SR). Response rate was 59% (120/203). 54 (45%) of patients had genetic testing ordered prior to their GC visit. There was a significant increase in GCOS score (mean 15.7 points) within 4 weeks post‐GC session (p<.0001) with no significant difference in GCOS change between patients who had genetic testing ordered previously and those attending pre‐test counseling (17.4 ± 18.2 versus. 14.1 ± 16 [p=.35]). Average CAQ score was high at baseline (1.67 ± 0.68), and there was a significant inverse relationship between pre‐GC CAQ score and extent of increase in GCOS score (p=.008) post‐GC. Controlling for baseline anxiety, there was a strong positive relationship between the WAI‐SR score and GCOS change (B = 0.80, 95% CI: 0.43, 1.17, p<.001). These results demonstrate a significant increase in empowerment after GC in ACM patients and that this outcome is not reliant on the ordering of a genetic test but instead sensitive to the quality of the genetic counselor:patient relationship. Genetic counselors can strive to further improve empowerment by focusing on reducing pre‐visit anxiety and alliance building with the patient.
Modelling the impact of HIV and HCV prevention and treatment interventions for people who inject drugs in Dar es Salaam, Tanzania
Authors: Fraser Hannah , Stone Jack , Wisse Ernst , Sambu Veryeh , Mfisi Peter , Duran Ivan J. , Soriano Mireia Aguirre , Walker Josephine G. , Makere Nobelrich , Luhmann Niklas , Kafura William , Nouvellet Maieule , Ragi Allan , Mundia Bernard , Vickerman Peter 
Published: October 2021

AbstractIntroductionPeople who inject drugs (PWID) in Dar es Salaam, Tanzania, have a high prevalence of HIV and hepatitis C virus (HCV). While needle and syringe programmes (NSP), opioid agonist therapy (OAT) and anti‐retroviral therapy (ART) are available in Tanzania, their coverage is sub‐optimal. We assess the impact of existing and scaled up harm reduction (HR) interventions on HIV and HCV transmission among PWID in Dar es Salaam.MethodsAn HIV and HCV transmission model among PWID in Tanzania was calibrated to data over 2006–2018 on HIV (∼30% and ∼67% prevalence in males and females in 2011) and HCV prevalence (∼16% in 2017), numbers on HR interventions (5254 ever on OAT in 2018, 766–1479 accessing NSP in 2017) and ART coverage (63.1% in 2015). We evaluated the impact of existing interventions in 2019 and impact by 2030 of scaling‐up the coverage of OAT (to 50% of PWID), NSP (75%, both combined termed “full HR”) and ART (81% with 90% virally suppressed) from 2019, reducing sexual HIV transmission by 50%, and/or HCV‐treating 10% of PWID infected with HCV annually.ResultsThe model projects HIV and HCV prevalence of 19.0% (95% credibility interval: 16.4–21.2%) and 41.0% (24.4–49.0%) in 2019, respectively. For HIV, 24.6% (13.6–32.6%) and 70.3% (59.3–77.1%) of incident infections among male and female PWID are sexually transmitted, respectively. Due to their low coverage (22.8% for OAT, 16.3% for NSP in 2019), OAT and NSP averted 20.4% (12.9–24.7%) of HIV infections and 21.7% (17.0–25.2%) of HCV infections in 2019. Existing ART (68.5% coverage by 2019) averted 48.1% (29.7–64.3%) of HIV infections in 2019. Scaling up to full HR will reduce HIV and HCV incidence by 62.6% (52.5–74.0%) and 81.4% (56.7–81.4%), respectively, over 2019–2030; scaled up ART alongside full HR will decrease HIV incidence by 66.8% (55.6–77.5%), increasing to 81.5% (73.7–87.5%) when sexual risk is also reduced. HCV‐treatment alongside full HR will decrease HCV incidence by 92.4% (80.7–95.8%) by 2030.ConclusionsCombination interventions, including sexual risk reduction and HCV treatment, are needed to eliminate HCV and HIV among PWID in Tanzania.
The potential and limitations of intrahepatic cholangiocyte organoids to study inborn errors of metabolism
Authors: Lehmann Vivian , Schene Imre F. , Ardisasmita Arif I. , Liv Nalan , Veenendaal Tineke , Klumperman Judith , van der Doef Hubert P. J. , Verkade Henkjan J. , Verstegen Monique M. A. , van der Laan Luc J. W. , Jans Judith J. M. , Verhoeven‐Duif Nanda M. , van Hasselt Peter M. , Nieuwenhuis Edward E. S. , Spee Bart , Fuchs Sabine A. 
Published: October 2021

AbstractInborn errors of metabolism (IEMs) comprise a diverse group of individually rare monogenic disorders that affect metabolic pathways. Mutations lead to enzymatic deficiency or dysfunction, which results in intermediate metabolite accumulation or deficit leading to disease phenotypes. Currently, treatment options for many IEMs are insufficient. Rarity of individual IEMs hampers therapy development and phenotypic and genetic heterogeneity suggest beneficial effects of personalized approaches. Recently, cultures of patient‐own liver‐derived intrahepatic cholangiocyte organoids (ICOs) have been established. Since most metabolic genes are expressed in the liver, patient‐derived ICOs represent exciting possibilities for in vitro modeling and personalized drug testing for IEMs. However, the exact application range of ICOs remains unclear. To address this, we examined which metabolic pathways can be studied with ICOs and what the potential and limitations of patient‐derived ICOs are to model metabolic functions. We present functional assays in patient ICOs with defects in branched‐chain amino acid metabolism (methylmalonic acidemia), copper metabolism (Wilson disease), and transporter defects (cystic fibrosis). We discuss the broad range of functional assays that can be applied to ICOs, but also address the limitations of these patient‐specific cell models. In doing so, we aim to guide the selection of the appropriate cell model for studies of a specific disease or metabolic process.
Untargeted plasma metabolomics identifies broad metabolic perturbations in glycogen storage disease type I
Authors: Mathis Tamara , Poms Martin , Köfeler Harald , Gautschi Matthias , Plecko Barbara , Baumgartner Matthias R. , Hochuli Michel 
Published: October 2021

AbstractBackgroundThe metabolic defect in glycogen storage disease type I (GSDI) results in fasting hypoglycemia and typical secondary metabolic abnormalities (eg, hypertriglyceridemia, hyperlactatemia, hyperuricemia). The aim of this study was to assess further perturbations of the metabolic network in GSDI patients under ongoing treatment.MethodsIn this prospective observational study, plasma samples of 14 adult patients (11 GSDIa, 3 GSDIb. Mean age 26.4 years, range 16‐46 years) on standard treatment were compared to a cohort of 31 healthy controls utilizing ultra‐high performance liquid chromatography (UHPLC) in combination with high resolution tandem mass spectrometry (HR‐MS/MS) and subsequent statistical multivariate analysis. In addition, plasma fatty acid profiling was performed by GC/EI‐MS.ResultsThe metabolomic profile showed alterations of metabolites in different areas of the metabolic network in both GSD subtypes, including pathways of fuel metabolism and energy generation, lipids and fatty acids, amino acid and methyl‐group metabolism, the urea cycle, and purine/pyrimidine metabolism. These alterations were present despite adequate dietary treatment, did not correlate with plasma triglycerides or lactate, both parameters typically used to assess the quality of metabolic control in clinical practice, and were not related to the presence or absence of complications (ie, nephropathy or liver adenomas).ConclusionThe metabolic defect of GSDI has profound effects on a variety of metabolic pathways in addition to the known typical abnormalities. These alterations are present despite optimized dietary treatment, which may contribute to the risk of developing long‐term complications, an inherent problem of GSDI which appears to be only partly modified by current therapy.
NK cell-based therapies for HIV infection: Investigating current advances and future possibilities
Authors: Perera Molligoda Arachchige Arosh S 
Published: October 2021

AbstractNK cells are well-known for their antiviral functions. Also, their role in HIV has been well established, with rapid responses elicited during early HIV infection. Most immune cells including CD4+ T cells, monocytes, Mϕs, and dendritic cells are readily infected by HIV. Recent evidence from multiple studies has suggested that similar to these cells, in chronic conditions like HIV, NK cells also undergo functional exhaustion with impaired cytotoxicity, altered cytokine production, and impaired ADCC. NK-based immunotherapy aims to successfully restore, boost, and modify their activity as has been already demonstrated in the field of cancer immunotherapy. The utilization of NK cell-based strategies for the eradication of HIV from the body provides many advantages over classical ART. The literature search consisted of manually selecting the most relevant studies from databases including PubMed, Embase, Google Scholar, and ClinicalTrial.gov. Some of the treatments currently under consideration are CAR-NK cell therapy, facilitating ADCC, TLR agonists, bNAbs, and BiKEs/TriKEs, blocking inhibitory NK receptors during infection, IL-15 and IL-15 superagonists (eg: ALT-803), and so on. This review aims to discuss the NK cell-based therapies currently under experimentation against HIV infection and finally highlight the challenges associated with NK cell-based immunotherapies.
Role of toll‐like receptors in modulation of cytokine storm signaling in SARS‐CoV‐2‐induced COVID‐19
Authors: Manik Moumita , Singh Rakesh K. 
Published: October 2021

AbstractBalanced immune regulation is crucial for recognizing an invading pathogen, its killing, and elimination. Toll‐like receptors (TLRs) are the key regulators of the innate immune system. It helps in identifying between self and nonself‐molecule and eventually eliminates the nonself. Endosomal TLR, mainly TLR3, TLR7, TLR8, and membrane‐bound TLR4, has a role in the induction of cytokine storms. TLR7/8 recognizes the ssRNA SARS‐COV‐2 and when it replicates to dsRNA, it is recognized by TLR3 and drives the TRIF‐mediated inflammatory signaling like NF‐κB, MAPK. Such signaling leads to significant transcription and translation of pro‐inflammatory genes, releasing inflammatory molecules into the systemic circulation, causing an imbalance in the system. So, whenever an imbalance occurs, a surge in the pro‐inflammatory mediators is observed in the blood, including cytokines like interleukin (IL)‐2, IL‐4, IL‐6, IL‐1β, IL‐8, interferon (IFN)‐γ, tumor necrosis factor (TNF)‐α. IL‐6 and IL‐1β are one of the driving factors for bringing the cytokine storm into the systemic circulation, which migrates into the other organs, causing multiple organ failures leading to the death of the individual with severe illness.
Development, construction, and validation of a thinner uniplanar calibration cage for radiostereometry
Authors: Jürgens‐Lahnstein Jonathan Hugo , Petersen Emil Toft , Laursen Mogens , Hauskov Iversen Christian , Kaptein Bart L. , Lindgren Lars , Stilling Maiken 
Published: October 2021

AbstractRadiostereometric analysis (RSA) is an accurate and precise radiographic method that can be used to measure micromotion of implants and study joint kinematics in vivo. A calibration cage with radiopaque markers is used to calibrate the RSA images; however, the thickness (250 mm) of the calibration cage restricts the available area for the patient and equipment during RSA recordings. A thinner calibration cage would increase the recording area, facilitate handling of the cage, and ease integration of the cage with the RSA system. We developed a thinner calibration cage without compromise of accuracy and precision. First, we performed numerical simulations of an RSA system, and showed that the calibration cage thickness could be decreased to 140 mm maintaining accuracy and precision using 40 fiducial and 30 control markers. Second, we constructed a new calibration cage (NRT cage) according to the simulation results. Third, we validated the new calibration cage against two state‐of‐the‐art calibration cages (Umeaa cage and Leiden cage) in a phantom study. All cages performed similar for marker‐based analysis, except for y‐rotation, where the Umeaa cage (SD = 0.064 mm) was less precise compared to the NRT (SD = 0.038 mm) and Leiden cages (0.042 mm) (p = .01). For model‐based analysis the NRT cage had superior precision for translations (SD ≤ 0.054 mm) over the Leiden cage (SD ≤ 0.118 mm) and Umeaa cage (SD ≤ 0.093 mm) (p < .01). The combined study confirmed that the new and thinner calibration cage maintained accuracy and precision at the level of existing thicker calibration cages.