bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Effects of Continuous Glucose Monitoring on Physical Activity Habits and Blood Lipid Levels in Persons With Type 1 Diabetes Managed With Multiple Daily Insulin Injections: An Analysis Based on the GOLD Randomized Trial (GOLD 8)
Authors: Nyström Thomas , Schwarz Erik , Dahlqvist Sofia , Wijkman Magnus , Ekelund Magnus , Holmer Helen , Bolinder Jan , Hellman Jarl , Imberg Henrik , Hirsch Irl B. , Lind Marcus
Published: June 2022

Background:

People with type 1 diabetes generally view it easier to exercise when having continuous information of the glucose levels. We evaluated whether patients with type 1 diabetes managed with multiple daily insulin injections (MDI) exercised more after initiating continuous glucose monitoring (CGM) and whether the improved glycemic control and well-being associated with CGM translates into improved blood lipids and markers of inflammation.

Method:

The GOLD trial was a randomized cross-over trial over 16 months where patients used either CGM or capillary self-monitoring of blood glucose (SMBG) over six months, with a four-month wash-out period between the two treatment periods. We compared grade of physical activity, blood lipids, apolipoproteins, and high-sensitivity C-reactive protein (hsCRP) levels during CGM and SMBG.

Results:

There were 116 patients with information of physical activity estimated by the International Physical Activity Questionnaire (IPAQ) during both CGM and SMBG. No changes were found during CGM or SMBG, IPAQ scores 3305 versus 3878 ( P = .16). In 136 participants with information of blood lipid levels with no change in lipid-lowering medication during the two treatment periods, HbA1c differed by 4.2 mmol/mol (NGSP 0.39%) between SMBG and CGM treatment ( P < .001). No significant changes existed in low-density lipoprotein, high-density lipoprotein, triglycerides, total cholesterol, apolipoprotein A1, apolipoprotein B1, or hsCRP, during CGM and SMBG.

Conclusion:

Although many patients experience it easier to perform physical activity when monitoring glucose levels with CGM, it does not influence the amount of physical activity in persons with type 1 diabetes. Blood lipids, apolipoprotein, and hsCRP levels were similar during CGM and SMBG.
Venous thromboembolism (VTE) prophylaxis following transurethral resection of the prostate (TURP): An audit of practice in Scotland
Authors: Small Robert Peter , Bhatt Jaimin
Published: June 2022

Objectives:

To establish the current practice of urologists in Scotland with regard to venous thromboembolism (VTE) prophylaxis following transurethral resection of the prostate (TURP).

Methods:

An electronic survey was distributed to all practicing urology consultants and trainees in Scotland. Participants were asked questions regarding their current practice with regard to peri-operative VTE prophylaxis and were offered free-text responses. Findings were compared with a previous UK-wide study from 2002, and with current European Association of Urology (EAU) guidelines.

Results:

56/113 (49.6%) of urologists responded to the survey. Overall, 71.4% of responding urologists prescribed pharmacological VTE prophylaxis following TURP. No urologists routinely prescribe VTE prophylaxis on discharge. 94.6% of responding urologists utilise mechanical prophylaxis in the form of thromboembolic deterrent (TED) stockings, with 35.7% of urologists discharging patients with TED stockings. No urologists reported a death from uncontrollable bleeding after TURP in the previous 10 years, whereas 10% of respondents had a patient whom had suffered a death or serious complication from a thromboembolic event following TURP in the past 10 years. A range of free-text responses were given.

Conclusion:

Our national audit has identified a wide variation between practice and current published guidance. These results contrast dramatically with a previous UK wide audit from 2002, which found 14% of urologists utilised pharmacological prophylaxis, 50% utilised mechanical prophylaxis only and 23% used no thromboprophylaxis at all. Recent guidance from the EAU recommends against using pharmacological prophylaxis due to the increased bleeding risk. Given that current practice does not marry with published recommendations; we believe that further research is required in this area for stronger evidence-based guidelines to be developed.

Level of evidence:

4
Antimicrobial resistance profiles for bacteria isolated from rectal swabs in patients candidate for prostate biopsy
Authors: Ohadian Moghadam Solmaz , Nowroozi Ali , Momeni Seyed Ali , Nowroozi Mohammad Reza , Heidarzadeh Siamak , Poorabhari Ashkan
Published: June 2022

Objective:

Infection is one of the common complications of post-prostate biopsy. Therefore, prophylaxis with fluoroquinolones and/or cephalosporins is recommended. We aimed to evaluate the prevalence of antibiotic-resistant bacteria isolated from rectal swabs in candidates for transrectal ultrasound-guided (TRUS) biopsy. The possible patient’s related risk factors attributing to resistance to antibiotics were also assessed.

Methods:

This cross-sectional study was performed on 126 male patients who were candidates for TRUS biopsy. Rectal swabs were collected and the samples were transferred to the laboratory in Amies transport medium during 2 hours and cultured on MacConkey agar with ciprofloxacin 1 mg/L and ciprofloxacin-resistant strains were identified. Kirby-Bauer disc diffusion method was used to determine the antibiotic susceptibility of the isolates.

Results:

In total, 59 bacterial isolates were obtained, which were Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa, respectively, in terms of frequency. They showed the lowest resistance to levofloxacin. Smoking was associated with positive culture results. Age was a factor with a significant effect on carrying ciprofloxacin-resistant strains.

Conclusion:

Ciprofloxacin resistance was high in almost all strains, but post-biopsy infectious complications were very low.

Level of evidence:

Not applicable
Determining risk factors for symptomatic urinary tract infection following trial of void: A retrospective analysis
Authors: Kwok Michael , Yaxley William , Ranasinghe Sachinka , Morton Leanne , Perera Sachin , Ponen Kreyen , Pelecanos Anita , Britton Sumudu , Harris Patrick NA , Paterson David L , Esler Rachel , Hussey David , Yaxley John W , Roberts Matthew J
Published: June 2022

Objective:

To investigate the incidence and risk factors for symptomatic urinary tract infection (UTI) following trial of void (TOV) to guide patient selection for antibiotic prophylaxis.

Methods:

A retrospective study considered all patients who underwent successful TOV across two separate 12-month periods at a tertiary hospital. Routine prophylactic antibiotics were not administered.

Results:

The 183 patients included were mostly men (91.3%) aged ⩾ 65 years (78.7%). Thirty-seven (20.3%) had recent urological surgery. The incidence of UTI following TOV was 12.6% (23/183); median duration of onset was 3 days (interquartile range = 2–9). Cystitis was most common (17/183; 9.3%), while four patients (2.2%) suffered urosepsis. There were no singular statistically significant risk factors for increasing the risk of UTI following TOV, however, ⩾ 2 risk factors showed numerically higher odds of UTI compared to ⩽ 1 risk factor (15.6% vs 4.2%; odds ratio = 4.24, 95% confidence interval = 0.96–18.80, p = 0.058). Atypical organisms resistant to most oral antibiotics were predominantly cultured, however, 89% sensitivity to ciprofloxacin was observed.

Conclusion:

The incidence of UTI following TOV was higher than anticipated. Reliable identification of at-risk patients for antibiotic prophylaxis is likely to be complicated. Further research is needed to confirm patient selection prior to confirmatory trials.

Level of evidence:

2b
Urban-Industrial Development and Regional Economic Growth in a Developing Country: A Spatial Econometric Approach
Authors: Guo Lingjun , Liu Yanran
Published: June 2022

This paper explored the effects of urbanization and industrial structure change in contemporary China using the data of 26 cities in the Yangtze River Delta (YRD) between 2006 and 2017. We analyzed the spatial characteristics of the regional economic growth by calculating the Global Moran’s I and the Local Moran’s I. We investigated the relationship between urbanization, industrial structure upgrade, and economic growth through a spatial econometric approach and tested the panel thresholds. Our findings included: (1) spatial autocorrelation is an important driver of urbanization and industrial structure upgrade; (2) the upgrade of the industrial structure leads to a structural economic deceleration which slows down the regional economic growth in the YRD; however, the positive effect of industrial structure upgrade on the regional economic growth still exists; (3) a synergy effect of New-type Urbanization and industrial structural upgrade positively affects the economic growth in the YRD; (4) the empirical results indicate that only when urbanization and industrial structural upgrade develop coordinately, will they play better roles in promoting the economic growth.
Association Between Landing Error Scoring System (LESS) Items and the Incidence Rate of Lower Extremity Stress Fracture
Authors: Cameron Kenneth L. , Peck Karen Y. , Davi Steven M. , Owens COL(ret) Brett D. , Svoboda COL(ret) Steven J. , DiStefano Lindsay J. , Marshall Stephen W. , de la Motte Sarah J. , Beutler COL(ret) Anthony I. , Padua Darin A.
Published: June 2022

Background:

Lower extremity stress fracture injuries are a major cause of morbidity in physically active populations. The ability to screen for modifiable risk factors associated with injury is critical in developing injury-prevention programs.

Purpose:

To determine if baseline Landing Error Scoring System (LESS) scores are associated with the incidence rate of lower extremity stress fracture.

Study Design:

Cohort study; Level of evidence, 2.

Methods:

A total of 1772 participants with no history of lower extremity stress fracture were included. At preinjury baseline, the authors conducted a lower extremity movement assessment during a jump-landing task using the LESS. Incident lower extremity stress fractures were identified during a 4-year follow-up period. Potential incident cases were reviewed by 2 sports medicine fellowship–trained orthopaedic surgeons blinded to baseline LESS data. Univariate and multivariable Poisson regression models were used to estimate the association between baseline total LESS scores, individual LESS items, and the incidence rate ratio (IRR) of lower extremity stress fracture.

Results:

A total of 94 incident lower extremity stress fractures were documented, for a 5.3% (95% CI, 4.3%-6.5%) cumulative incidence. The overall LESS score was associated with the incidence rate of lower extremity stress fracture. For every additional movement error documented at baseline, there was a 15% increase in the incidence rate of lower extremity stress fracture (IRR, 1.15 [95% CI, 1.02-1.31]; P = .025). In univariate analyses, ankle flexion, stance width, asymmetrical landing, and trunk flexion at initial contact, in addition to overall impression, were associated with the incidence rate of stress fracture. After controlling for sex and year of entry into the study cohort, participants who consistently landed flat-footed or heel-to-toe were 2.33 times (95% CI, 1.36-3.97; P = .002) more likely to sustain a lower extremity stress fracture. Similarly, participants who consistently demonstrated asymmetric landing at initial contact were 2.53 times (95% CI, 1.34-4.74; P = .004) more likely to sustain a stress fracture.

Conclusion:

Components of the LESS may be associated with increased lower extremity stress fracture risk and may be helpful in efficiently assessing high-risk lower extremity biomechanics in large groups.
Quality, Readability, and Accessibility of Online Content From a Google Search of “Macular Degeneration”: Critical Analysis
Authors: Hua Hong-Uyen , Rayess Nadim , Li Angela S. , Do Diana , Rahimy Ehsan
Published: June 2022

Purpose:

This work aims to assess the quality, accountability, readability, accessibility, and presence of Spanish translation in online material through a Google search of “macular degeneration”.

Methods:

In this retrospective cross-sectional analysis of website results from a Google search of “macular degeneration”, the quality and accountability for each website were assessed using the DISCERN criteria and the Health on the Net Foundation Code of Conduct (HONcode) principles. All 31 sites were independently graded by 2 ophthalmologists. Readability was evaluated using an online tool. The presence of accessibility features on the website and Spanish translation was recorded. The primary outcome measure was the DISCERN and HONcode quality and accountability scores of each website. Secondary outcome measures included the readability, accessibility, and presence of Spanish translation.

Results:

The mean ± SD of each criterion across all 15 DISCERN questions was 2.761 ± 0.666 (out of 5). The mean HONcode score for all websites was 7.355 ± 3.123. The mean consensus reading grade level was 10.258 ± 2.49. There were no statistically significant differences in any score between the top 5 websites and the bottom 26 websites evaluated. Accessibility was available on 10 of 31 websites. Spanish translation was available on 10 of 31 websites.

Conclusions:

The top 5 websites that appeared on a Google search did not have better quality or readability of online content. Improving quality, accountability, and readability can help improve patients’ health literacy regarding macular degeneration.
Ca2+ Signalling is a Conserved Game of Contact
Authors: Casbolt Hannah , Campanella Michelangelo
Published: June 2022

Apicoplasts are critical for the growth of medically important parasites. It is now reported that they form contacts with the endoplasmic reticulum (ER) via two pore channels thus enabling Ca2+ trafficking. This highlights the dynamic physical association between organelles as a critical motif in Ca2+ signaling.
The interaction between anti-PF4 antibodies and anticoagulants in vaccine-induced thrombotic thrombocytopenia
Authors: Singh Anurag , Toma Filip , Uzun Günalp , Wagner Teresa R. , Pelzl Lisann , Zlamal Jan , Freytag Verena , Weich Karoline , Nowak-Harnau Stefanie , Rothbauer Ulrich , Althaus Karina , Bakchoul Tamam
Published: June 2022

Life-threatening thrombotic events at unusual sites have been reported after vector-based vaccinations against severe acute respiratory syndrome coronavirus 2. This phenomenon is now termed vaccine-induced immune thrombotic thrombocytopenia (VITT). The pathophysiology of VITT is similar to that of heparin-induced thrombocytopenia (HIT) and is associated with platelet-activating antibodies (Abs) against platelet factor 4 (PF4). Therefore, current guidelines suggest nonheparin anticoagulants to treat VITT patients. In this study, we investigated the interactions of heparin, danaparoid, fondaparinux, and argatroban with VITT–Ab/PF4 complexes using an ex vivo model for thrombus formation as well as in vitro assays to analyze Ab binding and platelet activation. We found that immunoglobulin Gs (IgGs) from VITT patients induce increased adherent platelets/thrombus formation in comparison with IgGs from healthy controls. In this ex vivo flow-based model, the procoagulant activity of VITT IgGs was effectively inhibited with danaparoid and argatroban but also by heparin. Interestingly, heparin and danaparoid not only inhibited IgG binding to PF4 but were also able to effectively dissociate the preformed PF4/IgG complexes. Fondaparinux reduced the in vitro generation of procoagulant platelets and thrombus formation; however, it did not affect platelet aggregation. In contrast, argatroban showed no effect on procoagulant platelets and aggregation but significantly inhibited VITT-mediated thrombus formation. Taken together, our data indicate that negatively charged anticoagulants can disrupt VITT–Ab/PF4 interactions, which might serve as an approach to reduce Ab-mediated complications in VITT. Our results should be confirmed, however, in a clinical setting before a recommendation regarding the selection of anticoagulants in VITT patients could be made.
Unique characteristics of lung-resident neutrophils are maintained by PGE2/PKA/Tgm2-mediated signaling
Authors: Bae Geon Ho , Kim Ye Seon , Park Ji Ye , Lee Mingyu , Lee Sung Kyun , Kim Ji Cheol , Kim Jang Gyu , Shin Ye Ji , Lee Ho , Kim Soo-Youl , Bae Yong-Soo , Zabel Brian A. , Kim Hong Sook , Bae Yoe-Sik
Published: June 2022

Lung-resident neutrophils need to be tightly regulated to avoid degranulation- and cytokine-associated damage to fragile alveolar structures that can lead to fatal outcomes. Here we show that lung neutrophils (LNs) express distinct surface proteins and genes that distinguish LNs from bone marrow and blood neutrophils. Functionally, LNs show impaired migratory activity toward chemoattractants and produce high levels of interleukin-6 (IL-6) at steady state and low levels of tumor necrosis factor-α in response to lipopolysaccharide (LPS) challenge. Treating bone marrow neutrophils with bronchoalveolar lavage fluid or prostaglandin E2 induces LN-associated characteristics, including the expression of transglutaminase 2 (Tgm2) and reduced production of inflammatory cytokines upon LPS challenge. Neutrophils from Tgm2−/− mice release high levels of inflammatory cytokines in response to LPS. Lung damage is significantly exacerbated in Tgm2−/− mice in an LPS-induced acute respiratory distress syndrome model. Collectively, we demonstrate that prostaglandin E2 is a key factor for the generation of LNs with unique immune suppressive characteristics, acting through protein kinase A and Tgm2, and LNs play essential roles in protection of the lungs against pathogenic inflammation.
Comparative effectiveness of ZUMA-5 (axi-cel) vs SCHOLAR-5 external control in relapsed/refractory follicular lymphoma
Authors: Ghione Paola , Palomba M. Lia , Patel Anik R. , Bobillo Sabela , Deighton Kevin , Jacobson Caron A. , Nahas Myrna , Hatswell Anthony J. , Jung A. Scott , Kanters Steve , Snider Julia Thornton , Neelapu Sattva S. , Ribeiro Maria Teresa , Brookhart M. Alan , Ghesquieres Herve , Radford John , Gribben John G.
Published: June 2022

In the pivotal ZUMA-5 trial, axicabtagene ciloleucel (axi-cel; an autologous anti-CD19 chimeric antigen receptor T-cell therapy) demonstrated high rates of durable response in relapsed/refractory (r/r) follicular lymphoma (FL) patients. Here, outcomes from ZUMA-5 are compared with the international SCHOLAR-5 cohort, which applied key ZUMA-5 trial eligibility criteria simulating randomized controlled trial conditions. SCHOLAR-5 data were extracted from institutions in 5 countries, and from 1 historical clinical trial, for r/r FL patients who initiated a third or higher line of therapy after July 2014. Patient characteristics were balanced through propensity scoring on prespecified prognostic factors using standardized mortality ratio (SMR) weighting. Time-to-event outcomes were evaluated using weighted Kaplan-Meier analysis. Overall response rate (ORR) and complete response (CR) rate were compared using weighted odds ratios. The 143 ScHOLAR-5 patients reduced to an effective sample of 85 patients after SMR weighting vs 86 patients in ZUMA-5. Median follow-up time was 25.4 and 23.3 months for SCHOLAR-5 and ZUMA-5. Median overall survival (OS) and progression-free survival (PFS) in SCHOLAR-5 were 59.8 months and 12.7 months and not reached in ZUMA-5. Hazard ratios for OS and PFS were 0.42 (95% confidence interval [CI], 0.21-0.83) and 0.30 (95% CI, 0.18-0.49). The ORR and CR rate were 49.9% and 29.9% in SCHOLAR-5 and 94.2% and 79.1% in ZUMA-5, for odds ratios of 16.2 (95% CI, 5.6-46.9) and 8.9 (95% CI, 4.3-18.3). Compared with available therapies, axi-cel demonstrated an improvement in meaningful clinical endpoints, suggesting axi-cel addresses an important unmet need for r/r FL patients. This trial was registered at www.clinicaltrials.gov as #NCT03105336.
Comparative transcriptomic analysis reveals the molecular mechanism underlying seedling biomass heterosis in Brassica napus
Authors: Xiong Jie , Hu Kaining , Shalby Nesma , Zhuo Chenjian , Wen Jing , Yi Bin , Shen Jinxiong , Ma Chaozhi , Fu Tingdong , Tu Jinxing
Published: June 2022

Background

Heterosis is an important biological phenomenon in which the hybrids exceed the parents in many traits. However, the molecular mechanism underlying seedling heterosis remains unclear.

Results

In the present study, we analyzed the leaf transcriptomes of strong hybrids (AM, HM) and weak hybrids (CM, HW) and their parents (A, C, H, M, and W) at two periods. Phenotypically, hybrids had obvious biomass heterosis at the seedling stage, with statistically significant differences between the strong and weak hybrids. The transcriptomic analysis demonstrated that the number of differentially expressed genes (DEGs) between parents was the highest. Further analysis showed that most DEGs were biased toward parental expression. The biological processes of the two periods were significantly enriched in the plant hormone signal transduction and photosynthetic pathways. In the plant hormone signaling pathway, DEG expression was high in hybrids, with expression differences between strong and weak hybrids. In addition, DEGs related to cell size were identified. Similar changes were observed during photosynthesis. The enhanced leaf area of hybrids generated an increase in photosynthetic products, which was consistent with the phenotype of the biomass. Weighted gene co-expression network analysis of different hybrids and parents revealed that hub genes in vigorous hybrid were mainly enriched in the plant hormone signal transduction and regulation of plant hormones.

Conclusion

Plant hormone signaling and photosynthesis pathways, as well as differential expression of plant cell size-related genes, jointly regulate the dynamic changes between strong and weak hybrids and the generation of seedling-stage heterosis. This study may elucidate the molecular mechanism underlying early biomass heterosis and help enhance canola yield.
Arterial catheterization and in-hospital mortality in sepsis: a propensity score-matched study
Authors: Ou Qitian , Cai Gengxin , Zhou Yuan , Zha Wanjie , Huang Linqiang , Zeng Hongke , Jiang Wenqiang , Chen Shenglong , Wen Miaoyun
Published: June 2022

Background

Despite the extensive use of arterial catheterization (AC), clinical effectiveness of AC to alter the outcomes among patients with sepsis and septic shock has not been evaluated. The purpose of this study is to examine the association between the use of AC and in-hospital mortality in septic patients.

Methods

Adult patients with sepsis from Medical Information Mart for Intensive Care database were screened to conduct this retrospective observational study. Propensity score matching (PSM) was employed to estimate the relationship between arterial catheterization (AC) and in-hospital mortality. Multivariable logistic regression and inverse probability of treatment weighing (IPTW) were used to validate our findings.

Results

A total of 14,509 septic patients without shock and 4,078 septic shock patients were identified. 3,489 pairs in sepsis patients without shock and 589 pairs in septic shock patients were yielded respectively after PSM. For patients in the sepsis without shock group, AC placement was associated with increased in-hospital mortality (OR, 1.34; 95% CI, 1.17–1.54; p < 0.001). In the septic shock group, there was no significant difference in hospital mortality between AC group and non-AC group. The results of logistic regression and propensity score IPTW model support our findings.

Conclusions

In hemodynamically stable septic patients, AC is independently associated with higher in-hospital mortality, while in patients with septic shock, AC was not associated with improvements in hospital mortality.
Major cardiovascular events after bone marrow mononuclear cell transplantation following acute myocardial infarction: an updated post-BAMI meta-analysis of randomized controlled trials
Authors: Attar Armin , Hosseinpour Alireza , Hosseinpour Hamidreza , Kazemi Asma
Published: June 2022

Background

The effect of bone marrow-derived mononuclear cells (BM-MNCs) after acute myocardial infarction (AMI) on myocardial function indices such as left ventricular ejection fraction has been widely studied. However, the effect of this intervention on major adverse cardiovascular events (MACE) was not the principal purpose of most investigations and its role is unclear. The aim of this study was to investigate the possible long-term clinical efficacy of BM-MNCs on MACE after AMI.

Methods

A comprehensive search was conducted through electronic databases for potentially eligible randomized trials investigating the impact of BM-MNC therapy following acute MI on clinical outcomes. Risk of bias of the eligible studies was assessed using the Cochrane Collaboration’s tool. The effect of treatment was displayed by risk ratio (RR) and its 95% confidence interval (CI) using random-effects model.

Results

Initial database searching found 1540 records and 23 clinical trials with a total of 2286 participants eligible for meta-analysis. Injection of BM-MNCs was associated with lower risk of composite end points of hospitalization for congestive heart failure (CHF), re-infarction, and cardiac-related mortality (91/1191 vs. 111/812, RR = 0.643, 95% CI = 0.489 to 0.845, p = 0.002). This effect was derived from both reduction of CHF (47/1220 vs. 62/841, RR = 0.568, 95% CI = 0.382 to 0.844, p = 0.005) and re-infarction rate (23/1159 vs. 30/775, RR = 0.583, 95% CI = 0.343 to 0.991, p = 0.046), but not cardiac-related mortality (28/1290 vs. 31/871, RR = 0.722, 95% CI = 0.436 to 1.197, p = 0.207).

Conclusion

This is the first meta-analysis focused on the cardiovascular outcomes of stem cell therapy after AMI and it revealed that transplantation of BM-MNCs may reduce composite endpoint of hospitalization for CHF, re-infarction, and cardiac related mortality driven mainly by reducing reinfarction and hospitalization for heart failure rates but not cardiovascular mortality.
An investigation of penalization and data augmentation to improve convergence of generalized estimating equations for clustered binary outcomes
Authors: Geroldinger Angelika , Blagus Rok , Ogden Helen , Heinze Georg
Published: June 2022

Background

In binary logistic regression data are ‘separable’ if there exists a linear combination of explanatory variables which perfectly predicts the observed outcome, leading to non-existence of some of the maximum likelihood coefficient estimates. A popular solution to obtain finite estimates even with separable data is Firth’s logistic regression (FL), which was originally proposed to reduce the bias in coefficient estimates. The question of convergence becomes more involved when analyzing clustered data as frequently encountered in clinical research, e.g. data collected in several study centers or when individuals contribute multiple observations, using marginal logistic regression models fitted by generalized estimating equations (GEE). From our experience we suspect that separable data are a sufficient, but not a necessary condition for non-convergence of GEE. Thus, we expect that generalizations of approaches that can handle separable uncorrelated data may reduce but not fully remove the non-convergence issues of GEE.

Methods

We investigate one recently proposed and two new extensions of FL to GEE. With ‘penalized GEE’ the GEE are treated as score equations, i.e. as derivatives of a log-likelihood set to zero, which are then modified as in FL. We introduce two approaches motivated by the equivalence of FL and maximum likelihood estimation with iteratively augmented data. Specifically, we consider fully iterated and single-step versions of this ‘augmented GEE’ approach. We compare the three approaches with respect to convergence behavior, practical applicability and performance using simulated data and a real data example.

Results

Our simulations indicate that all three extensions of FL to GEE substantially improve convergence compared to ordinary GEE, while showing a similar or even better performance in terms of accuracy of coefficient estimates and predictions. Penalized GEE often slightly outperforms the augmented GEE approaches, but this comes at the cost of a higher burden of implementation.

Conclusions

When fitting marginal logistic regression models using GEE on sparse data we recommend to apply penalized GEE if one has access to a suitable software implementation and single-step augmented GEE otherwise.
Prevalence of chronic kidney diseases and its determinants among Iranian adults: results of the first phase of Shahedieh cohort study
Authors: Dehghani Ali , Alishavandi Sadegh , Nourimajalan Nader , Fallahzadeh Hossein , Rahmanian Vahid
Published: June 2022

Background

Chronic kidney disease (CKD) is one of the major global causes of mortality, described as the most neglected chronic disease. This study aimed to determine the prevalence and determinants of CKD in the setting of the Shahedieh cohort study in Yazd, Iran.

Methods

This cross-sectional study was conducted on adults in the baseline phase of the Shahedieh cohort study in Yazd, Iran. In this study, 9781 participants aged 30–73-year-old were investigated. The data used in this study included demographic and clinical variables and blood samples. Adjusted odds ratios were employed using multivariate logistic regression; meanwhile, population attributable risks for CKD were calculated and reported.

Results

CKD prevalence was 27.5% (95%CI: 26.57–28.34) in all participants, 24% in male, and 30.3% in female. The results of multivariate logistic regression analysis identified age (OR = 1.89, 95%CI:1.082–1.96), women (OR = 1.62, 95%CI: 1.45–1.79), BMI ≥ 30 (OR = 1.40,95%CI: 1.20–1.62), diabetes (OR = 1.38, 95%CI: 1.22–1.57), hypertriglyceridemia(OR = 1.20, 95%CI: 1.01–1.43), history of cardiovascular disease (OR = 1.20, 95%CI: 1.01–1.43), hypertension (OR = 1.18, 95%CI: 1.04–1.33), smoking (OR = 1.17, 95% CI: 1.02–1.33), LDL ≥ 130 (OR = 1.15, 95%CI: 1.01–1.31), history of kidney stone (OR = 1.14, 95%CI: 1.01–1.32) and hypercholesterolemia (OR = 1.14, 95%CI: 1.01–1.32) as risk factors for CKD. Among individual factors, obesity (11.25%), Hypertriglyceridemia (9.21%), LDL ≥ 130 (7.12%) had the greatest Population-Attributable Fraction, followed by Hypercholesterolemia (5.2%), diabetes (5.05%), smoking (3.73%) and high blood pressure (2.82%).

Conclusion

The results showed that the main determinants of CKD are potentially modifiable risk factors. Therefore, implementing early detection and screening programs in people at risk as well as preventive measures such as lifestyle modification programs and risk factors controlling can prevent the disease.
Surrogate biomarkers of outcome for wake-up ischemic stroke
Authors: Hervella Pablo , Alonso-Alonso María Luz , Pérez-Mato María , Rodríguez-Yáñez Manuel , Arias-Rivas Susana , López-Dequidt Iria , Pumar José M. , Sobrino Tomás , Campos Francisco , Castillo José , Iglesias-Rey Ramón
Published: June 2022

Background

Wake-up ischemic stroke (IS) has been usually excluded from acute stroke therapy options for being outside of the safe treatment window. We identified risk factors, and clinical or molecular biomarkers that could be therapeutic targets for wake-up stroke prevention, thus hopefully leading to a decrease in its mortality and disability in medium to long-term outcome.

Methods

4251 ischemic stroke (IS) patients from a prospectively registered database were recruited; 3838 (90.3%) had known onset-symptom time, and 413 (9.7%) were wake-up strokes. The main endpoint was to analyze the association between different serum biomarkers with wake-up IS episodes and their progression. Leukocytes count, serum levels of C-reactive protein, fibrinogen, interleukin 6 (IL-6), and vitamin D were analyzed as inflammation biomarkers; N-terminal pro-B-type Natriuretic-Peptide and microalbuminuria, used as atrial/endothelial dysfunction biomarkers; finally, glutamate levels as excitotoxicity biomarker. In addition, demographic, clinical and neuroimaging variables associated with the time-evolution of wake-up IS patients and functional outcome at 3 months were evaluated. Good and poor functional outcome were defined as mRS ≤2 and mRS > 2 at 3 months, respectively.

Results

Wake-up IS showed a poorer outcome at 3-months than in patients with known on-set-symptom time (59.1% vs. 48.1%; p < 0.0001). Patients with wake-up IS had higher levels of inflammation biomarkers; IL-6 levels at admission (51.5 ± 15.1 vs. 27.8 ± 18.6 pg/ml; p < 0.0001), and low vitamin D levels at 24 h (5.6 ± 5.8 vs. 19.2 ± 9.4 ng/ml; p < 0.0001) are worthy of attention. In a logistic regression model adjusted for vitamin D, OR was 15.1; CI 95%: 8.6–26.3, p < 0.0001. However, we found no difference in vitamin D levels between patients with or without clinical-DWI mismatch (no: 18.95 ± 9.66; yes: 17.84 ± 11.77 ng/mL, p = 0.394). No difference in DWI volume at admission was found (49.3 ± 96.9 ml in wake-up IS patients vs. 51.7 ± 98.2 ml in awake IS patients; p = 0.895).

Conclusions

Inflammatory biomarkers are the main factors that are strongly associated with wake-up IS episodes. Wake-up IS is associated with lower vitamin D levels. These data indicate that vitamin D deficiency could become a therapeutic target to reduce wake-up IS events.
Meta-analysis of diagnostic cell-free circulating microRNAs for breast cancer detection
Authors: Sehovic Emir , Urru Sara , Chiorino Giovanna , Doebler Philipp
Published: June 2022

Background

Breast cancer (BC) is the most frequently diagnosed cancer among women. Numerous studies explored cell-free circulating microRNAs as diagnostic biomarkers of BC. As inconsistent and rarely intersecting microRNA panels have been reported thus far, we aim to evaluate the overall diagnostic performance as well as the sources of heterogeneity between studies.

Methods

Based on the search of three online search engines performed up to March 21st 2022, 56 eligible publications that investigated diagnostic circulating microRNAs by utilizing Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) were obtained. Primary studies’ potential for bias was evaluated with the revised tool for the quality assessment of diagnostic accuracy studies (QUADAS-2). A bivariate generalized linear mixed-effects model was applied to obtain pooled sensitivity and specificity. A novel methodology was utilized in which the sample and study models’ characteristics were analysed to determine the potential preference of studies for sensitivity or specificity.

Results

Pooled sensitivity and specificity of 0.85 [0.81—0.88] and 0.83 [0.79—0.87] were obtained, respectively. Subgroup analysis showed a significantly better performance of multiple (sensitivity: 0.90 [0.86—0.93]; specificity: 0.86 [0.80—0.90]) vs single (sensitivity: 0.82 [0.77—0.86], specificity: 0.83 [0.78—0.87]) microRNA panels and a comparable pooled diagnostic performance between studies using serum (sensitivity: 0.87 [0.81—0.91]; specificity: 0.83 [0.78—0.87]) and plasma (sensitivity: 0.83 [0.77—0.87]; specificity: 0.85 [0.78—0.91]) as specimen type. In addition, based on bivariate and univariate analyses, miRNA(s) based on endogenous normalizers tend to have a higher diagnostic performance than miRNA(s) based on exogenous ones. Moreover, a slight tendency of studies to prefer specificity over sensitivity was observed.

Conclusions

In this study the diagnostic ability of circulating microRNAs to diagnose BC was reaffirmed. Nonetheless, some subgroup analyses showed between-study heterogeneity. Finally, lack of standardization and of result reproducibility remain the biggest issues regarding the diagnostic application of circulating cell-free microRNAs.
Post-recurrence survival analysis in patients with oligo-recurrence after curative esophagectomy
Authors: Tsai Ping-Chung , Chien Hung-Che , Hsu Po-Kuei , Hung Jung-Jyh , Huang Chien-Sheng , Hsu Wen-Hu , Hsu Han-Shui
Published: June 2022

Background

Recurrent esophageal cancer is associated with dismal prognosis. There is no consensus about the role of surgical treatments in patients with limited recurrences. This study aimed to evaluate the role of surgical resection in patients with resectable recurrences after curative esophagectomy and to identify their prognostic factors.

Methods

We retrospectively reviewed patients with recurrent esophageal cancer after curative esophagectomy between 2004 and 2017 and included those with oligo-recurrence that was amenable for surgical intent. The prognostic factors of overall survival (OS) and post-recurrence survival (PRS), as well as the survival impact of surgical resection, were analyzed.

Results

Among 654 patients after curative esophagectomies reviewed, 284 (43.4%) had disease recurrences. The recurrences were found resectable in 63 (9.6%) patients, and 30 (4.6%) patients received surgery. The significant prognostic factors of PRS with poor outcome included mediastinum lymph node (LN) recurrence and pathologic T3 stage. In patients with and without surgical resection for recurrence cancer, the 3-year OS rates were 65.6 and 47.6% (p = 0.108), while the 3-year PRS rates were 42.9 and 23.5% (p = 0.100). In the subgroup analysis, surgery for resectable recurrence, compared with non-surgery, could achieve better PRS for patients without any comorbidities (hazard ratio 0.36, 95% CI: 0.14 to 0.94, p = 0.038).

Conclusions

Mediastinum LN recurrence or pathologic T3 was associated with worse OS and PRS in patients with oligo-recurrences after curative esophagectomies. No definite survival benefit was noted in patients undergoing surgery for resectable recurrence, except in those without comorbidities.
Analysis of the completeness of self-harm and suicide records in Pernambuco, Brazil, 2014–2016
Authors: da Fonsêca Jéssica Ramalho , de Oliveira Conceição Maria , de Castro Cláudia Cristina Lima , da Costa Heitor Victor Veiga , Galvão Pauliana Valéria Machado , da Costa Ceballos Albanita Gomes , do Bonfim Cristine Vieira
Published: June 2022

Introduction

Suicides and suicide attempts are major public health problems, and coping strategies are hampered by insufficient or inadequate notifications. Data accuracy influences the formulation of public and mental health policies and suicide prevention strategies. The objective of this study was to analyze the completeness of self-harm and suicide records in the state of Pernambuco, Brazil, 2014–2016.

Methods

This is an evaluative study with a descriptive design. The data were collected from suicide attempt records from the Notifiable Diseases Information System and suicide records from the Mortality Information System. Probabilistic linkage was used to relate these databases, and the degree of completeness of the variables was calculated. Completeness was classified into the following categories: good (≥ 75.1%), regular (50.1%–75.0%), low (25.1%–50.0%), and very low (≤ 25.0%).

Results

In the analyzed period, 1,404 notifications of self-harm were studied, with an overall mean completeness of 86.2%. In addition, 1,050 suicide records were analyzed, with an overall mean completeness of 95.8%. Most variables referring to suicide attempts had good completeness, with the exception of the variables “occupation” and “education.” The completeness of all suicide-related variables was rated as good. After linkage, a significant improvement was observed in the degree of completeness of the variable “occupation”.

Conclusion

The results of this study showed that the completeness of self-harm and suicide variables improved from the first to the last year. The integration of data from different information systems provides an opportunity to improve suicide prevention programs and the quality of available information. Continuous efforts to increase the completeness and reliability of suicide surveillance systems are fundamental to describe the epidemiological profile and, consequently, plan preventive actions, in addition to contributing to the development and reformulation of strategies aimed at reducing morbidity and mortality related to suicidal behavior.
Clinical characteristics and risk factors predictive of pulmonary embolism complicated in bronchiectasis patients: a retrospective study
Authors: Deng Tiantian , Xu Ke , Wu Beishou , Sheng Fei , Li Xu , Zhu Zhuxian , Zhang Ziqiang
Published: June 2022

Objective

Pulmonary embolism (PE) is a rare complication in bronchiectasis (BE) patients associated with a high rate of mortality and morbidity. However, data regarding bronchiectasis patients complicated with PE are limited. Early diagnosis of PE in bronchiectasis patients can improve the prognosis, this study aimed to investigate the clinical features and potential risk factors for early diagnosis of PE in bronchiectasis patients.

Methods

Data of Patients were collected from Tongji Hospital of Tongji University of China. Bronchiectasis patients complicated with pulmonary embolism were named as BE/PE group (n = 63), as well as contemporaneous aged- and sex-matched bronchiectasis patients without pulmonary embolism named as BE group (n = 189), at a ratio of 1:3(cases to controls). Clinical parameters and risk factors were analyzed.

Results

Univariate analysis shows that long-term bed rest, chronic lung disease, autoimmune disease, peripheral artery disease (PAD), tuberculosis history, dyspnea, blood homocysteine, CD4/CD8 ratio, or SIQIIITIII syndrome were closely correlated with the incidence of PE in the bronchiectasis patients (p < 0.05). Multivariate logistic regression analysis of significant variables showed that CD4/CD8 ratio (OR 1.409, 95% CI 1.045–1.901) and autoimmune disease (OR 0.264, 95% CI 0.133–0.524) are independent risk factors for BE/PE patients, compared with the BE patients. 53 out of 189 (28.0%) BE patients had hemoptysis, and 15 out of 63 (23.8%) BE/PE patients had hemoptysis (p > 0.05).

Conclusions

The coexistence of pulmonary embolism and bronchiectasis are rarely encountered and easily to be ignored. Early identification of the clinical characteristic and potential risk factors of pulmonary embolism in bronchiectasis patients may help optimize the treatment strategies.
Retention of bar clip attachment for mandibular implant overdenture
Authors: Nassar Hossam I. , Abdelaziz Medhat Sameh
Published: June 2022

Objectives

The aim of the present study was to evaluate the retention and loss of retention after fatigue testing at different time intervals between two types of bar clip materials (digitally designed PEEK bar clip and regular Nylon bar clip).

Materials and methods

An epoxy model was constructed for a completely edentulous mandible. Two implants were placed according to prosthetically driven implant placement by a computer-guided surgical stent. Bar clips were digitally designed, 3D printed, and pressed into Poly Ether Ether Ketone (PEEK). Pick up of PEEK and nylon clips was performed on the dentures fitting surface using self-cured acrylic resin. Each study group was subjected to an insertion and removal fatigue test simulating 3 years of patient usage. Retention values were recorded using the universal testing machine at initial retention and after 1, 2, and 3 years of simulated usage. For proper sample sizing, 24 models and dentures (12 for each group) were used. An independent sample t-test and repeated measures analysis of variance were used to compare the data.

Results

There were statistically significant differences in retention between the PEEK and nylon bar clips at the beginning of the experiment (p = 0.000*). But after 3 years of simulated use, there was no significant difference in retention between the test groups (p = 0.055, NS). After 3 years of simulated use, the retention of PEEK clips decreased by − 58.66% recording 17.37 ± 1.07 N, while the retention of nylon clip increased by + 2.99% recording 16.56 ± 0.88 N.

Conclusion

The digitally designed PEEK clip showed comparable retention results to the nylon clip after 3 years of simulated use.

Clinical relevance

Maintenance of bar attachment with PEEK clip offers a clinical solution after the wear of normal plastic clips, which is a cheap solution that is easily fabricated and picked up into the denture. Digital fabricated PEEK bar retentive inserts can be used in cases of bar attachment wear.
Nitrogen fixation by diverse diazotrophic communities can support population growth of arboreal ants
Authors: Nepel Maximilian , Pfeifer Josephine , Oberhauser Felix B. , Richter Andreas , Woebken Dagmar , Mayer Veronika E.
Published: June 2022

Background

Symbiotic ant-plant associations, in which ants live on plants, feed on plant-provided food, and protect host trees against threats, are ubiquitous across the tropics, with the Azteca-Cecropia associations being amongst the most widespread interactions in the Neotropics. Upon colonization of Cecropia’s hollow internodes, Azteca queens form small patches with plant parenchyma, which are then used as waste piles when the colony grows. Patches—found in many ant-plant mutualisms—are present throughout the colony life cycle and may supplement larval food. Despite their initial nitrogen (N)-poor substrate, patches in Cecropia accommodate fungi, nematodes, and bacteria. In this study, we investigated the atmospheric N2 fixation as an N source in patches of early and established ant colonies.

Results

Via 15N2 tracer assays, N2 fixation was frequently detected in all investigated patch types formed by three Azteca ant species. Quantified fixation rates were similar in early and established ant colonies and higher than in various tropical habitats. Based on amplicon sequencing, the identified microbial functional guild—the diazotrophs—harboring and transcribing the dinitrogenase reductase (nifH) gene was highly diverse and heterogeneous across Azteca colonies. The community composition differed between early and established ant colonies and partly between the ant species.

Conclusions

Our data show that N2 fixation can result in reasonable amounts of N in ant colonies, which might not only enable bacterial, fungal, and nematode growth in the patch ecosystems but according to our calculations can even support the growth of ant populations. The diverse and heterogeneous diazotrophic community implies a functional redundancy, which could provide the ant-plant-patch system with a higher resilience towards changing environmental conditions. Hence, we propose that N2 fixation represents a previously unknown potential to overcome N limitations in arboreal ant colonies.