bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of LC3-associated phagocytosis in COPD and in response to cigarette smoke
Authors: Asare Patrick F. , Tran Hai B. , Hurtado Plinio R. , Perkins Griffith B. , Nguyen Phan , Jersmann Hubertus , Roscioli Eugene , Hodge Sandra 
Published: December 2021

Introduction/Rationale: In chronic obstructive pulmonary disease (COPD), defective macrophage phagocytic clearance of cells undergoing apoptosis by efferocytosis may lead to secondary necrosis of the uncleared cells and contribute to airway inflammation. The precise mechanisms for this phenomenon remain unknown. LC3-associated phagocytosis (LAP) is indispensable for effective efferocytosis. We hypothesized that cigarette smoke inhibits the regulators of LAP pathway, potentially contributing to the chronic airways inflammation associated with COPD. Methods: Bronchoalveolar (BAL)-derived alveolar macrophages, lung tissue macrophages obtained from lung resection surgery, and monocyte-derived macrophages (MDM) were prepared from COPD patients and control participants. Lung/airway samples from mice chronically exposed to cigarette smoke were also investigated. Differentiated THP-1 cells were exposed to cigarette smoke extract (CSE). The LAP pathway including Rubicon, as an essential regulator of LAP, efferocytosis and inflammation was examined using western blot, ELISA, flow cytometry, and/or immunofluorescence. Results: Rubicon was significantly depleted in COPD alveolar macrophages compared with non-COPD control macrophages. Rubicon protein in alveolar macrophages of cigarette smoke-exposed mice and cigarette smoke-exposed MDM and THP-1 was decreased with a concomitant impairment of efferocytosis. We also noted increased expression of LC3 which is critical for LAP pathway in COPD and THP-1 macrophages. Furthermore, THP-1 macrophages exposed to cigarette smoke extract exhibited higher levels of other key components of LAP pathway including Atg5 and TIM-4. There was a strong positive correlation between Rubicon protein expression and efferocytosis. Conclusion: LAP is a requisite for effective efferocytosis and an appropriate inflammatory response, which is impaired by Rubicon deficiency. Our findings suggest dysregulated LAP due to reduced Rubicon as a result of CSE exposure. This phenomenon could lead to a failure of macrophages to effectively process phagosomes containing apoptotic cells during efferocytosis. Restoring Rubicon protein expression has unrecognized therapeutic potential in the context of disease-related modifications caused by exposure to cigarette smoke.
Assessing the Structural and Functional Similarity of Insulin Glargine Biosimilars
Authors: Vishwakarma Gayatri , Nupur Neh , Rathore Anurag S. 
Published: December 2021

Background: A biosimilar product is expected to exhibit similar safety, efficacy, and quality as that of the approved reference product. Only a few reports of thorough evaluation of the quality of insulin glargine biosimilars are available in literature. Here, we examine the structural and functional similarity of biosimilars of insulin glargine, the first basal long-acting insulin analogue with respect to its innovator product (Lantus® from Sanofi Aventis). Methods: Structural similarity was established using mass spectrometry, chromatographic, and spectroscopic techniques. Stability was compared by performing accelerated thermal stress studies. Functional similarity was established via in vitro assay. Results: Biosimilar 4 exhibited greater content of high molecular weight species (HMWs) (0.80%) and related substances (RS) (0.45±0.06%) vs others (HMWs of 0.04% and RS of 0.17%). Biosimilars 1 and 3 exhibited higher rate of impurity generation (0.78% and 0.73% per week, respectively), as compared with other drug products (0.02% to 0.43% per week). Furthermore, %aggregation at 14 days was found to statistically correlate ( R2= 0.99, root mean square error (RMSE) = 0.095) with %aggregation at 0 day (linearly) and the number of months from expiry (nonlinearly), highlighting the overpowering impact of the latter. Conclusions: While an overall structural and functional similarity was observed across insulin glargine biosimilars with respect to the innovator product, low amounts of product-related variants were seen in some biosimilars and these impact product stability. The %aggregation at 14 days exhibits statistical correlation with %aggregation at 0 day and the number of months from expiry. The order of biosimilarity was denoted as Lantus®>Biosimilar 2>Biosimilar 4>Biosimilar 1>Biosimilar 3.
Assessing the clinical impact and resource use of a 30-minute chlamydia and gonorrhoea point-of-care test at three sexual health services
Authors: Huntington Susie , Weston Georgie , Adams Elisabeth 
Published: December 2021

Objectives: To assess clinical metrics and resource use of a 30-minute point-of-care test (POCT) for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) compared to laboratory-based testing. Methods: Three English sexual health services (SHSs) were recruited as part of a study. Existing processes for CT/NG testing and treatment were assessed, and adaptions to incorporate the CT/NG POCT were developed during semi-structured interviews. Staff time and consumables data were collected by clinic staff prior to and following introduction of the POCT. Results: SHSs selected patient groups for whom the CT/NG POCT would be used. Testing and treatment process data were collected for 225 patients (n = 118 POC; n = 107 standard). The percentage of patients receiving unnecessary CT treatment was 5% (5/95) and 13% (12/93) for POC and standard care respectively. The average CT/NG pathway cost varied and was on average £61.55 for POC and £50.88 for standard care. For the two SHSs where the POCT was used during a patient’s visit, for standard and POC respectively, the average time to CT treatment was 10.0 and 0.0 days and to NG treatment, 0.3 and 0.0 days. Conclusion: Use of a 30-minute POCT at three SHSs yielded clinical benefits by reducing time to treatment and unnecessary CT treatment.
Return-to-Sport Outcomes After Primary Ulnar Collateral Ligament Reconstruction With Palmaris Versus Hamstring Tendon Grafts: A Systematic Review
Authors: Trofa David P. , Constant Michael , Crutchfield Connor R. , Dantzker Nicholas J. , Saltzman Bryan M. , Lynch T. Sean , Ahmad Christopher S. 
Published: December 2021

Background: Ulnar collateral ligament (UCL) reconstruction is the current gold standard of treatment for overhead athletes with a symptomatic, deficient UCL of the elbow who have failed nonoperative treatment and wish to return to sport (RTS) at a high level. The palmaris longus and hamstring tendons are common graft choices, but no study has analyzed the existing literature to assess whether one graft is superior to the other. Purpose: To systematically report on the outcomes of UCL reconstruction using palmaris and hamstring autografts. Study Design: Systematic review; Level of evidence, 4. Methods: A combination of the terms “ulnar collateral ligament,” “valgus instability,” “Tommy John surgery,” “hamstring,” and “palmaris longus” were searched in PubMed, Embase, and the Cochrane Library. RTS and return-to-same-level (RSL) rates, patient-reported outcomes, and complications were included for analysis. We used the modified Coleman Methodology Score and risk-of-bias tool for nonrandomized studies to assess the quality of the included studies. Results: This review included 6 studies (combined total of 2154 elbows) that directly compared palmaris and hamstring graft use in UCL reconstruction. Follow-up ranged from 24 to 80.4 months, and the mean patient age across all studies was 21.8 years. The mean RSL across all studies and grafts was 79.0%, and the mean RTS was 84.1%, consistent with results previously reported in the literature. The mean RTS and RSL rates for the palmaris graft group were 84.6% and 82%, respectively; the hamstring graft group showed mean RTS and RSL rates of 80.8% and 80.8%. Meta-analysis revealed no significant difference in RSL between the 2 graft groups (odds ratio, 1.06; 95% CI, 0.77-1.46). The combined complication rate of the included studies was 18.2%, with failure rates ranging from 0% to 7.1%. Conclusion: Results of this review indicated that both palmaris and hamstring tendon grafts are viable options for primary UCL reconstruction. Graft choice should be determined by a combination of patient and surgeon preference.
Association of clonal hematopoiesis with chronic obstructive pulmonary disease
Authors: Miller Peter G. , Qiao Dandi , Rojas-Quintero Joselyn , Honigberg Michael C. , Sperling Adam S. , Gibson Christopher J. , Bick Alexander G. , Niroula Abhishek , McConkey Marie E. , Sandoval Brittany , Miller Brian C. , Shi Weiwei , Viswanathan Kaushik , Leventhal Matthew , Werner Lillian , Moll Matthew , Cade Brian E. , Barr R. Graham , Correa Adolfo , Cupples L. Adrienne , Gharib Sina A. , Jain Deepti , Gogarten Stephanie M. , Lange Leslie A. , London Stephanie J. , Manichaikul Ani , O’Connor George T. , Oelsner Elizabeth C. , Redline Susan , Rich Stephen S. , Rotter Jerome I. , Ramachandran Vasan , Yu Bing , Sholl Lynette , Neuberg Donna , Jaiswal Siddhartha , Levy Bruce D. , Owen Caroline A. , Natarajan Pradeep , Silverman Edwin K. , van Galen Peter , Tesfaigzi Yohannes , Cho Michael H. , Ebert Benjamin L. ,   for the COPDGene Study Investigators, National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine Consortium
Published: December 2021

Abstract
Chronic obstructive pulmonary disease (COPD) is associated with age and smoking, but other determinants of the disease are incompletely understood. Clonal hematopoiesis of indeterminate potential (CHIP) is a common, age-related state in which somatic mutations in clonal blood populations induce aberrant inflammatory responses. Patients with CHIP have an elevated risk for cardiovascular disease, but the association of CHIP with COPD remains unclear. We analyzed whole-genome sequencing and whole-exome sequencing data to detect CHIP in 48 835 patients, of whom 8444 had moderate to very severe COPD, from four separate cohorts with COPD phenotyping and smoking history. We measured emphysema in murine models in which Tet2 was deleted in hematopoietic cells. In the COPDGene cohort, individuals with CHIP had risks of moderate-to-severe, severe, or very severe COPD that were 1.6 (adjusted 95% confidence interval [CI], 1.1-2.2) and 2.2 (adjusted 95% CI, 1.5-3.2) times greater than those for noncarriers. These findings were consistently observed in three additional cohorts and meta-analyses of all patients. CHIP was also associated with decreased FEV1% predicted in the COPDGene cohort (mean between-group differences, −5.7%; adjusted 95% CI, −8.8% to −2.6%), a finding replicated in additional cohorts. Smoke exposure was associated with a small but significant increased risk of having CHIP (odds ratio, 1.03 per 10 pack-years; 95% CI, 1.01-1.05 per 10 pack-years) in the meta-analysis of all patients. Inactivation of Tet2 in mouse hematopoietic cells exacerbated the development of emphysema and inflammation in models of cigarette smoke exposure. Somatic mutations in blood cells are associated with the development and severity of COPD, independent of age and cumulative smoke exposure.
Comorbid insomnia and sleep apnoea is associated with all-cause mortality
Authors: Lechat Bastien , Appleton Sarah , Melaku Yohannes Adama , Hansen Kristy , McEvoy R. Doug , Adams Robert , Catcheside Peter , Lack Leon , Eckert Danny J. , Sweetman Alexander 
Published: December 2021

BackgroundIncreased mortality has been reported in people with insomnia and in those with obstructive sleep apnoea (OSA). However, these conditions commonly co-occur and the combined effect of comorbid insomnia and sleep apnoea (COMISA) on mortality risk is unknown. This study used Sleep Heart Health Study (SHHS) data to assess associations between COMISA and all-cause mortality risk.MethodsInsomnia was defined as difficulties falling asleep, maintaining sleep and/or early morning awakenings from sleep ≥16 times per month, and daytime impairments. OSA was defined as an apnoea–hypopnoea index ≥15 events·h−1. COMISA was defined if both conditions were present. Multivariable adjusted Cox proportional hazards models were used to determine the association between COMISA and all-cause mortality (n=1210) over 15 years of follow-up.Results5236 participants were included. 2708 (52%) did not have insomnia/OSA (reference group), 170 (3%) had insomnia-alone, 2221 (42%) had OSA-alone and 137 (3%) had COMISA. COMISA participants had a higher prevalence of hypertension (OR 2.00, 95% CI 1.39–2.90) and cardiovascular disease (CVD) (OR 1.70, 95% CI 1.11–2.61) compared with the reference group. Insomnia-alone and OSA-alone were associated with higher risk of hypertension but not CVD compared with the reference group. Compared with the reference group, COMISA was associated with a 47% (hazard ratio 1.47, 95% CI 1.06–2.07) increased risk of mortality. The association between COMISA and mortality was consistent across multiple definitions of OSA and insomnia.ConclusionsCOMISA was associated with higher rates of hypertension and CVD at baseline, and an increased risk of all-cause mortality compared with no insomnia/OSA.
An international survey on the use of intrapleural tissue plasminogen activator/DNase therapy for pleural infection
Authors: Lau Estee P.M. , Eshraghi Matin , Dootson Kirstie , Yeoh Cindy , Ywe Phu Wint , Lee Y.C. Gary , Popowicz Natalia D. 
Published: December 2021

IntroductionIntrapleural tissue plasminogen activator (tPA) combined with human recombinant DNase (DNase) could be an effective alternative to surgery in managing pleural infection, as demonstrated in the Multi-centre Intrapleural Sepsis Trial (MIST)-2. However, the optimal delivery regimen is still unknown. The aim of this survey was to identify the current practice of tPA/DNase use by physicians with published interests in pleural infection, and their opinions on dose de-escalation of tPA/DNase therapy.MethodsPotential participants were identified using four search strategies. Only practising physicians who were managing patients with pleural infections and either actively involved in pleural research and publications, or were members of relevant pleural disease guideline panels at the time of survey were included.ResultsAn invitation email with the questionnaire was sent to 102 participants, of whom 49 (48%) responded. Most respondents (90%, n=44) have used tPA/DNase to manage pleural infection, but the dosing and delivery regimens employed varied. Many (86%, 38 out of 44) respondents have used 10 mg tPA, while 73% (n=32), 16% (n=7) and 9% (n=4) have used 5 mg, 2.5 mg and 1 mg doses, respectively. Most respondents instilled tPA/DNase concurrently (61%, n=27) and routinely administered six doses of tPA/DNase (52%, n=23) twice daily (82%, n=36). Respondents would consider using a lower starting dose of tPA (with the possibility of escalation if clinically needed) if a median 80% (interquartile range 50–80%) of patients could be successfully treated at that dose.ConclusionThis survey observed a large variation in the current treatment protocol of intrapleural tPA/DNase therapy worldwide and the need for more data on this subject.
Breast-cancer detection using blood-based infrared molecular fingerprints
Authors: Kepesidis Kosmas V. , Bozic-Iven Masa , Huber Marinus , Abdel-Aziz Nashwa , Kullab Sharif , Abdelwarith Ahmed , Al Diab Abdulrahman , Al Ghamdi Mohammed , Hilal Muath Abu , Bahadoor Mohun R. K. , Sharma Abhishake , Dabouz Farida , Arafah Maria , Azzeer Abdallah M. , Krausz Ferenc , Alsaleh Khalid , Zigman Mihaela , Nabholtz Jean-Marc 
Published: December 2021

Abstract
Background
Breast cancer screening is currently predominantly based on mammography, tainted with the occurrence of both false positivity and false negativity, urging for innovative strategies, as effective detection of early-stage breast cancer bears the potential to reduce mortality. Here we report the results of a prospective pilot study on breast cancer detection using blood plasma analyzed by Fourier-transform infrared (FTIR) spectroscopy – a rapid, cost-effective technique with minimal sample volume requirements and potential to aid biomedical diagnostics. FTIR has the capacity to probe health phenotypes via the investigation of the full repertoire of molecular species within a sample at once, within a single measurement in a high-throughput manner. In this study, we take advantage of cross-molecular fingerprinting to probe for breast cancer detection.

Methods
We compare two groups: 26 patients diagnosed with breast cancer to a same-sized group of age-matched healthy, asymptomatic female participants. Training with support-vector machines (SVM), we derive classification models that we test in a repeated 10-fold cross-validation over 10 times. In addition, we investigate spectral information responsible for BC identification using statistical significance testing.

Results
Our models to detect breast cancer achieve an average overall performance of 0.79 in terms of area under the curve (AUC) of the receiver operating characteristic (ROC). In addition, we uncover a relationship between the effect size of the measured infrared fingerprints and the tumor progression.

Conclusion
This pilot study provides the foundation for further extending and evaluating blood-based infrared probing approach as a possible cross-molecular fingerprinting modality to tackle breast cancer detection and thus possibly contribute to the future of cancer screening.
A national population-based study of patients, bystanders and contextual factors associated with resuscitation in witnessed cardiac arrest: insight from the french RéAC registry
Authors: Reuter Paul-Georges , Baert Valentine , Colineaux Hélène , Escutnaire Joséphine , Javaud Nicolas , Delpierre Cyrille , Adnet Frédéric , Loeb Thomas , Charpentier Sandrine , Lapostolle Frédéric , Hubert Hervé , Lamy Sébastien 
Published: December 2021

Abstract
Background
In out-of-hospital cardiac arrest (OHCA), bystander initiated cardiopulmonary resuscitation (CPR) increases the chance of return of spontaneous circulation and survival with a favourable neurological status. Socioeconomic disparities have been highlighted in OHCA field. In areas with the lowest average socioeconomic status, OHCA incidence increased, and bystander CPR decreased. Evaluations were performed on restricted geographical area, and European evaluation is lacking. We aimed to analyse, at a national level, the impact of area-level social deprivation on the initiation of CPR in case of a witnessed OHCA.

Methods

We included all witnessed OHCA cases with age over 18 years from July 2011 to July 2018 form the OHCA French national registry. We excluded OHCA occurred in front of rescue teams or in nursing home, and patients with incomplete address or partial geocoding. We collected data from context, bystander and patient. The area-level social deprivation was estimated by the French version of the European Deprivation Index (in quintile) associated with the place where OHCA occurred. We assessed the associations between Utstein variables and social deprivation level using a mixed-effect logit model with bystander-initiated CPR.

Results
We included 23,979 witnessed OHCA of which 12,299 (51%) had a bystander-initiated CPR. More than one third of the OHCA (8,326 (35%)) occurred in an area from the highest quintile of social deprivation. The higher the area-level deprivation, the less the proportion of bystander-initiated CPR (56% in Quintile 1 versus 48% in Quintile 5). The In the multivariable analysis, bystander less often began CPR in areas with the highest deprivation level, compared to those with the lowest deprivation level (OR=0.69, IC95%: 0.63-0.75).

Conclusions
The level of social deprivation of the area where OHCA occurred was associated with bystander-initiated CPR. It decreased in the more deprived areas although these areas also concentrate more younger patients.
Serum interleukin-17 predicts severity and prognosis in patients with community acquired pneumonia: a prospective cohort study
Authors: Feng Chun-Mei , Wang Xin-Ming , Li Meng-Die , Xu Zheng , Hua Dong-Xu , Cheng Jia-Yi , Zheng Ling , Zhao Hui , Fu Lin 
Published: December 2021

Abstract
Background
Some studies previously demonstrated that interleukin-17 (IL-17) involves in pulmonary diseases progression. Nevertheless, the role of IL-17 in community-acquired pneumonia (CAP) remains unknown. This study aims to examine the correlations between serum IL-17 with the severity and prognosis in CAP patients through a prospective cohort study.

Methods
All 239 CAP patients were recruited. Serum IL-17 was detected by enzyme-linked immunosorbent assay (ELISA). The CAP severity was evaluated through CAP severity scores, including CURB-65, CRB-65, PSI, SMART-COP, CURXO and APACHE II.

Results
Serum IL-17 was gradually increased consistent with the severity of CAP. Correlative analysis suggested that serum IL-17 was associated with clinical physiologic indicators among CAP patients. Logistic regression indicated that serum IL-17 was positively related to CAP severity scores. Additionally, the prognostic outcomes were tracked among CAP patients. The levels of IL-17 on admission were significantly increased in CAP patients with ICU admission, mechanical ventilation, vasoactive agent, death and longer hospitalization days. Logistic regression analyses revealed serum higher IL-17 on admission elevated the risks of vasoactive agent usage and longer hospital stays in CAP patients. The cut-off concentrations of serum IL-17 for death, ICU admission, mechanical ventilation and ≥ 14 hospital stays were 86.80 ng/mL, 84.92 ng/mL, 84.92 ng/mL and 60.29 ng/mL respectively.

Conclusions
Serum IL-17 on admission is positively associated with the severity and poor prognosis among CAP patients, revealing that IL-17 may implicate in the pathological process of CAP. Therefore, serum IL-17 may become an effective biomarker for diagnosis, prognosis and therapy for CAP patients.