bluuebunny/crossref_metadata_2025 huggingface dataset:
Computed tomography-guided cutting needle biopsy for lung nodules: when the biopsy-based benign results are real benign
Authors: Hui Hui , Ma Gao-Lei , Yin Hai-Tao , Zhou Yun , Xie Xiao-Mei , Gao Yong-Guang
Published: June 2022

Background

Computed tomography (CT)-guided cutting needle biopsy (CNB) is an effective diagnostic method for lung nodules (LNs). The false-negative rate of CT-guided lung biopsy is reported to be up to 16%. This study aimed to determine the predictors of true-negative results in LNs with CNB-based benign results.

Methods

From January 2011 to December 2015, 96 patients with CNB-based nonspecific benign results were included in this study as the training group to detect predictors of true-negative results. From January 2016 to December 2018, an additional 57 patients were included as a validation group to test the reliability of the predictors.

Results

In the training group, a total of 96 patients underwent CT-guided CNB for 96 LNs. The CNB-based results were true negatives for 82 LNs and false negatives for 14 LNs. The negative predictive value of the CNB-based benign results was 85.4% (82/96). Univariate and multivariate logistic regression analyses revealed that CNB-based granulomatous inflammation (P = 0.013, hazard ratio = 0.110, 95% confidential interval = 0.019–0.625) was the independent predictor of true-negative results. The area under the receiver operator characteristic (ROC) curve was 0.697 (P = 0.019). In the validation group, biopsy results for 47 patients were true negative, and 10 were false negative. When the predictor was used on the validation group, the area under the ROC curve was 0.759 (P = 0.011).

Conclusions

Most of the CNB-based benign results were true negatives, and CNB-based granulomatous inflammation could be considered a predictor of true-negative results.
Activation of α7 nicotinic acetylcholine receptor retards the development of endometriosis
Authors: Hao Meihua , Liu Xishi , Guo Sun-Wei
Published: June 2022

Background

Women with endometriosis have been shown to have a reduced vagal tone as compared with controls and vagotomy promoted while vagus nerve stimulation (VNS) decelerated the progression of endometriosis in mice. Extensive research also has shown that the activation of the cholinergic anti-inflammatory pathway by VNS activates α7 nicotinic acetylcholine receptor (α7nAChR), potently reducing inflammation. Yet whether α7nAChR plays any role in endometriosis is unknown. We evaluated its expression in normal endometrium, ovarian and deep endometriotic lesions, and evaluated its role in the development of endometriosis.

Methods

Immunohistochemistry analyses of α7nAChR in endometriotic lesions as well as control endometrium, and quantification of tissue fibrosis by Masson trichrome staining were performed. Mouse experiments were conducted to evaluate the impact of α7nAChR activation or suppression on lesional progression and possible therapeutic effect. Finally, in vitro experiments were conducted to evaluate the effect of activation of α7nAChR on epithelial-mesenchymal transition (EMT), fibroblast-to-myofibroblast transdifferentiation (FMT), smooth muscle metaplasia (SMM) and fibrogenesis in an endometriotic epithelial cell line and primary endometriotic stromal cells derived from ovarian endometrioma tissue samples.

Results

Immunostaining of α7nAChR was significantly reduced in human endometriotic epithelial cells as compared with their counterpart in normal endometrium. Lesional α7nAChR staining levels correlated negatively with lesional fibrosis and the severity of dysmenorrhea. The α7nAChR agonist significantly impeded the development of endometriotic lesions in mouse models possibly through hindrance of EMT and FMT. It also demonstrated therapeutic effects in mice with induced deep endometriosis. Treatment of endometriotic epithelial and stromal cells with an α7nAChR agonist significantly abrogated platelet-induced EMT, FMT and SMM, and suppressed cellular contractility and collagen production.

Conclusions

α7nAChR is suppressed in endometriotic lesions, and its activation by pharmacological means can impede EMT, FMT, SMM, and fibrogenesis of endometriotic lesions. As such, α7nAChR can be rightfully viewed as a potential target for therapeutic invention.

Trial registration

Not applicable.
Implementing a health labour market analysis to address health workforce gaps in a rural region of India
Authors: Garg Samir , Tripathi Narayan , McIsaac Michelle , Zurn Pascal , Zapata Tomas , Mairembam Dilip S. , Singh Niharika Barik , de Graeve Hilde
Published: June 2022

Background

Human Resources for Health (HRH) are essential for making meaningful progress towards universal health coverage (UHC), but health systems in most of the developing countries continue to suffer from serious gaps in health workforce. The Global Strategy on Human Resources for Health—Workforce 2030, adopted in 2016, includes Health Labor Market Analysis (HLMA) as a tool for evidence based health workforce improvements. HLMA offers certain advantages over the traditional approach of workforce planning. In 2018, WHO supported a HLMA exercise in Chhattisgarh, one of the predominantly rural states of India.

Methods

The HLMA included a stakeholder consultation for identifying policy questions relevant to the context. The HLMA focused on state HRH at district-level and below. Mixed methods were used for data collection and analysis. Detailed district-wise data on HRH availability were collected from state’s health department. Data were also collected on policies implemented on HRH during the 3 year period after the start of HLMA and changes in health workforce.

Results

The state had increased the production of doctors but vacancies persisted until 2018. The availability of doctors and other qualified health workers was uneven with severe shortages of private as well as public HRH in rural areas. In case of nurses, there was a substantial production of nurses, particularly from private schools, however there was a lack of trusted accreditation mechanism and vacancies in public sector persisted alongside unemployment among nurses. Based on the HLMA, pragmatic recommendations were decided and followed up. Over the past 3 years since the HLMA began an additional 4547 health workers including 1141 doctors have been absorbed by the public sector. The vacancies in most of the clinical cadres were brought below 20%.

Conclusion

The HLMA played an important role in identifying the key HRH gaps and clarifying the underlying issues. The HLMA and the pursuant recommendations were instrumental in development and implementation of appropriate policies to improve rural HRH in Chhattisgarh. This demonstrates important progress on key 2030 Global Strategy milestones of reducing inequalities in access to health workers and improving financing, retention and training of HRH.
Glioblastoma microenvironment contains multiple hormonal and non-hormonal growth-stimulating factors
Authors: Dahlberg Daniel , Rummel Jutta , Distante Sonia , De Souza Gustavo Antonio , Stensland Maria Ekman , Mariussen Espen , Rootwelt Helge , Voie Øyvind , Hassel Bjørnar
Published: June 2022

Background

The growth of malignant tumors is influenced by their microenvironment. Glioblastoma, an aggressive primary brain tumor, may have cysts containing fluid that represents the tumor microenvironment. The aim of this study was to investigate whether the cyst fluid of cystic glioblastomas contains growth-stimulating factors. Identification of such growth factors may pave the way for the development of targeted anti-glioblastoma therapies.

Methods

We performed hormone analysis of cyst fluid from 25 cystic glioblastomas and proteomics analysis of cyst fluid from another 12 cystic glioblastomas.

Results

Glioblastoma cyst fluid contained hormones within wide concentration ranges: Insulin-like growth factor 1 (0–13.7 nmol/L), insulin (1.4–133 pmol/L), erythropoietin (4.7–402 IU/L), growth hormone (0–0.93 µg/L), testosterone (0.2–10.1 nmol/L), estradiol (0–1.0 nmol/L), triiodothyronine (1.0–11.5). Tumor volume correlated with cyst fluid concentrations of growth hormone and testosterone. Survival correlated inversely with cyst fluid concentration of erythropoietin. Several hormones were present at concentrations that have been shown to stimulate glioblastoma growth in vitro. Concentrations of erythropoietin and estradiol (in men) were higher in cyst fluid than in serum, suggesting formation by tumor or brain tissue. Quantitatively, glioblastoma cyst fluid was dominated by serum proteins, illustrating blood–brain barrier leakage. Proteomics identified several proteins that stimulate tumor cell proliferation and invasiveness, others that inhibit apoptosis or mediate adaption to hypoxia and some that induce neovascularization or blood–brain barrier leakage.

Conclusion

The microenvironment of glioblastomas is rich in growth-stimulating factors that may originate from the circulation, the tumor, or the brain. The wide variation in cyst fluid hormone concentrations may differentially influence tumor growth.
A plant tethering system for the functional study of protein-RNA interactions in vivo
Authors: Cuerda-Gil Diego , Hung Yu-Hung , Panda Kaushik , Slotkin R. Keith
Published: June 2022

The sorting of RNA transcripts dictates their ultimate post-transcriptional fates, such as translation, decay or degradation by RNA interference (RNAi). This sorting of RNAs into distinct fates is mediated by their interaction with RNA-binding proteins. While hundreds of RNA binding proteins have been identified, which act to sort RNAs into different pathways is largely unknown. Particularly in plants, this is due to the lack of reliable protein-RNA artificial tethering tools necessary to determine the mechanism of protein action on an RNA in vivo. Here we generated a protein-RNA tethering system which functions on an endogenous Arabidopsis RNA that is tracked by the quantitative flowering time phenotype. Unlike other protein-RNA tethering systems that have been attempted in plants, our system circumvents the inadvertent triggering of RNAi. We successfully in vivo tethered a protein epitope, deadenylase protein and translation factor to the target RNA, which function to tag, decay and boost protein production, respectively. We demonstrated that our tethering system (1) is sufficient to engineer the downstream fate of an RNA, (2) enables the determination of any protein’s function upon recruitment to an RNA, and (3) can be used to discover new interactions with RNA-binding proteins.
Intermediate-risk pulmonary embolism: echocardiography predictors of clinical deterioration
Authors: Weekes Anthony J. , Fraga Denise N. , Belyshev Vitaliy , Bost William , Gardner Christopher A. , O’Connell Nathaniel S.
Published: June 2022

Background

We determine the predictive value of transthoracic echocardiographic (TTE) metrics for clinical deterioration within 5 days in adults with intermediate-risk pulmonary embolism (PE).

Methods

This was a prospective observational study of intermediate-risk PE patients. To determine associations of TTE and clinical predictors with clinical deterioration, we used univariable analysis, Youden’s index for optimal thresholds, and multivariable analyses to report odds ratios (ORs) or area under the curve (AUC).

Results

Of 306 intermediate-risk PE patients, 115 (37.6%) experienced clinical deterioration. PE patients who had clinical deterioration within 5 days had greater baseline right ventricle (RV) dilatation and worse systolic function than the group without clinical deterioration as indicated by the following: RV basal diameter 4.46 ± 0.77 versus 4.20 ± 0.77 cm; RV/LV basal width ratio 1.14 ± 0.29 versus 1.02 ± 0.24; tricuspid annular plane systolic excursion (TAPSE) 1.56 ± 0.55 versus 1.80 ± 0.52 cm; and RV systolic excursion velocity 10.40 ± 3.58 versus 12.1 ± 12.5 cm/s, respectively. Optimal thresholds for predicting clinical deterioration were: RV basal width 3.9 cm (OR 2.85 [1.64, 4.97]), RV-to-left ventricle (RV/LV) ratio 1.08 (OR 3.32 [2.07, 5.33]), TAPSE 1.98 cm (OR 3.3 [2.06, 5.3]), systolic excursion velocity 10.10 cm/s (OR 2.85 [1.75, 4.63]), and natriuretic peptide 190 pg/mL (OR 2.89 [1.81, 4.62]). Significant independent predictors were: transient hypotension 6.1 (2.2, 18.9), highest heart rate 1.02 (1.00, 1.03), highest respiratory rate 1.02 (1.00, 1.04), and RV/LV ratio 1.29 (1.14, 1.47). By logistic regression and random forest analyses, AUCs were 0.80 (0.73, 0.87) and 0.78 (0.70, 0.85), respectively.

Conclusions

Basal RV, RV/LV ratio, and RV systolic function measurements were significantly different between intermediate-risk PE patients grouped by subsequent clinical deterioration.
Association of annual hospital septic shock case volume and hospital mortality
Authors: Chen Yan , Ma Xu-dong , Kang Xiao-hui , Gao Si-fa , Peng Jin-min , Li Shan , Liu Da-wei , Zhou Xiang , Weng Li , Du Bin ,   China National Critical Care Quality Control Center Group
Published: June 2022

Background

The burden of sepsis remains high in China. The relationship between case volume and hospital mortality among patients with septic shock, the most severe complication of sepsis, is unknown in China.

Methods

In this retrospective cohort study, we analyzed surveillance data from a national quality improvement program in intensive care units (ICUs) in China in 2020. Association between septic shock case volume and hospital mortality was analyzed using multivariate linear regression and restricted cubic splines.

Results

We enrolled a total of 134,046 septic shock cases in ICUs from 1902 hospitals in China during 2020. In this septic shock cohort, the median septic shock volume per hospital was 33 cases (interquartile range 14–76 cases), 41.4% were female, and more than half of the patients were over 61 years old, with average hospital mortality of 21.2%. An increase in case volume was associated with improved survival among septic shock cases. In the linear regression model, the highest quartile of septic shock volume was associated with lower hospital mortality compared with the lowest quartile (β − 0.86; 95% CI − 0.98, − 0.74; p < 0.001). Similar differences were found in hospitals of respective geographic locations and hospital levels. With case volume modeled as a continuous variable in a restricted cubic spline, a lower volume threshold of 40 cases before which a substantial reduction of the hospital mortality rate was observed.

Conclusions

The findings suggest that hospitals with higher septic shock case volume have lower hospital mortality in China. Further research is needed to explain the mechanism of this volume–outcome relationship.
Intravenous tocilizumab for the treatment of giant cell arteritis: a phase Ib dose-ranging pharmacokinetic bridging study
Authors: Schmitt Christophe , Brockwell Laura , Giraudon Mylène , Zucchetto Mauro , Christ Lisa , Bannert Bettina , Daikeler Thomas , Villiger Peter M.
Published: June 2022

Background

Subcutaneous tocilizumab (TCZ SC) is approved globally for giant cell arteritis (GCA). This phase Ib study investigated the pharmacokinetics, pharmacodynamics, safety, and exploratory efficacy of intravenous (IV) TCZ 6 and 7 mg/kg in patients with GCA. This study explored an IV dose resulting in a minimum exposure level within the range of effective trough concentrations achieved with TCZ SC dosing in GCA and not exceeding the exposure of the well-tolerated 8 mg/kg IV every 4 weeks (Q4W) in rheumatoid arthritis (RA).

Methods

Patients with GCA who had received ≥ 5 doses of TCZ IV 8 mg/kg Q4W and achieved remission were enrolled. Patients received 5 doses of TCZ IV 7 mg/kg Q4W in period 1 and, if still in remission, 5 doses of 6 mg/kg Q4W in period 2. Pharmacokinetic endpoints were maximum concentration (Cmax), minimum concentration (Ctrough), area under the curve over a dosing interval (AUCτ), and mean concentration (Cmean) of TCZ after the last dose of each period. Other endpoints included pharmacodynamic markers, safety, and exploratory efficacy.

Results

In 24 patients, the median (range) age was 65.5 (57–90) years, and 62.5% were female. TCZ exposures (Cmax and AUCτ) were 11.2% and 20.0% lower at the 6- than 7-mg/kg dose. The mean interleukin 6 (IL-6) serum concentrations were elevated at baseline and remained elevated, with slightly higher concentrations in period 1 than in period 2. The mean serum soluble IL-6 receptor concentrations were elevated at baseline and comparable between the 2 doses at steady state. C-reactive protein levels and most erythrocyte sedimentation rates were within normal ranges throughout the study. Overall, 22 patients (91.7%) had ≥ 1 adverse event, and 4 (16.7%) had a serious adverse event. No patients experienced a GCA flare, and all remained in remission throughout the study.

Conclusions

Both doses of TCZ IV Q4W were generally well tolerated in patients with GCA. The Cmax and Cmean achieved with 6 mg/kg IV Q4W in patients with GCA were similar to those in patients with RA treated with 8 mg/kg IV Q4W, and Ctrough was within the range observed in patients with GCA treated with SC dosing every week or every 2 weeks.

Trial registration

ClinicalTrials.gov, NCT03923738
Quantification of SNAP-25 with mass spectrometry and Simoa: a method comparison in Alzheimer’s disease
Authors: Nilsson Johanna , Ashton Nicholas J. , Benedet Andrea L. , Montoliu-Gaya Laia , Gobom Johan , Pascoal Tharick A. , Chamoun Mira , Portelius Erik , Jeromin Andreas , Mendes Muriel , Zetterberg Henrik , Rosa-Neto Pedro , Brinkmalm Ann , Blennow Kaj
Published: June 2022

Background

Synaptic dysfunction and degeneration are central to Alzheimer’s disease (AD) and have been found to correlate strongly with cognitive decline. Thus, studying cerebrospinal fluid (CSF) biomarkers reflecting synaptic degeneration, such as the presynaptic protein synaptosomal-associated protein 25 (SNAP-25), is of importance to better understand the AD pathophysiology.

Methods

We compared a newly developed Single molecule array (Simoa) immunoassay for SNAP-25 with an in-house immunoprecipitation mass spectrometry (IP-MS) method in a well-characterized clinical cohort (n = 70) consisting of cognitively unimpaired (CU) and cognitively impaired (CI) individuals with and without Aβ pathology (Aβ+ and Aβ−).

Results

A strong correlation (Spearman’s rank correlation coefficient (rs) > 0.88; p < 0.0001) was found between the Simoa and IP-MS methods, and no statistically significant difference was found for their clinical performance to identify AD pathophysiology in the form of Aβ pathology. Increased CSF SNAP-25 levels in CI Aβ+ compared with CU Aβ− (Simoa, p ≤ 0.01; IP-MS, p ≤ 0.05) and CI Aβ− (Simoa, p ≤ 0.01; IP-MS, p ≤ 0.05) were observed. In independent blood samples (n = 32), the Simoa SNAP-25 assay was found to lack analytical sensitivity for quantification of SNAP-25 in plasma.

Conclusions

These results indicate that the Simoa SNAP-25 method can be used interchangeably with the IP-MS method for the quantification of SNAP-25 in CSF. Additionally, these results confirm that CSF SNAP-25 is increased in relation to amyloid pathology in the AD continuum.
Incidental findings on coronary computed tomography in women with selected reproductive disorders
Authors: van der Ham Kim , van Zwol-Janssens Charissa , Velthuis Birgitta K. , Koster Maria P. H. , Louwers Yvonne V. , Goei Dustin , Blomjous Maurits S. H. , Franx Arie , Fauser Bart C. J. M. , Boersma Eric , Laven Joop S. E. , Budde Ricardo P. J. ,   the CREW Consortium
Published: June 2022

Objective

To determine the prevalence of incidental findings (IFs) on coronary computed tomography (CCT) in women aged 45–55 years and previously diagnosed with reproductive disorders such as polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI) or preeclampsia (PE).

Methods

A total of 486 middle-aged women with PCOS (n = 101), POI (n = 97) or a history of PE (n = 288) underwent a CCT as part of a prior prospective study. IFs were categorized by their significance (minor, moderate and major). Follow-up information was collected from patients’ records. To investigate the impact of different field of views (FOVs), a subset of scans was analyzed in full FOV and small FOV.

Results

In 96/486 (19.8%) women, one or more IFs were detected, of which 54/486 (11.1%) were classified as moderate/major and 48/486 (9.9%) required follow-up. A moderate/major IF was detected in 16/101 (15.9%) women with PCOS, 13/97 (13.4%) women with POI and 25/288 (8.7%) women with a history of PE. In 78 women with an IF detected in the full FOV, the IF was still visible in 60 (76.9%) women in the small FOV. In the full FOV, 46 women required follow-up, but using the small FOV this was reduced to 30 women.

Conclusion

Using CCT as a cardiovascular disease screening tool in women with selected reproductive disorders increases the probability of detecting IFs that can cause anxiety and may generate extra costs, but can also reveal clinically relevant findings. Using a small FOV centered around the heart resulted in a lower prevalence of IFs and required less follow-up.
Appetite ratings and ghrelin concentrations in young adults after administration of a balanced meal. Does sex matter?
Authors: Leone Alessandro , De Amicis Ramona , Pellizzari Marta , Bertoli Simona , Ravella Simone , Battezzati Alberto
Published: June 2022

Background

Sex-based differences in appetite ratings have been observed previously. Ghrelin is the only known orexigenic peptide hormone. Sex differences in postprandial ghrelin responses may underlie different perceptions of hunger and satiety, but results are conflicting. We conducted a parallel study to evaluate sex differences in postprandial appetite ratings and ghrelin concentration after administration of a physiological meal among students of University of Milan.

Methods

Twenty-four healthy, normal weight volunteers (12 men and 12 women) aged 18–35 years were recruited. A balanced mixed meal meeting 40% of the estimated daily energy expenditure and providing 60% of calories from carbohydrates, 25% from lipids and 15% from protein was administrated. Sex differences in appetite ratings (satiety, hunger, fullness and desire to eat) and magnitude of ghrelin suppression during postprandial period (up to 180 min) were determined.

Results

In the fasting state, men and women did not differ in appetite ratings and ghrelin concentrations. After feeding, women tended to reach peak of satiety earlier than men, who in turn reached the nadir of hunger later than women (median: 30 min, interquartile range (IQR): 1; 120 vs. 1 min, IQR 1; 1, p = 0.007). Ghrelin suppression was greater in women (median decremental AUC − 95, IQR − 122; − 66) than in men (median decremental AUC − 47, IQR − 87; − 31, p = 0.041).

Conclusions

These findings suggest sex differences in the postprandial appetite regulation that might be important for nutritional strategy to prevent and treat obesity and eating disorders.
The diagnostic potential of oxidative stress biomarkers for preeclampsia: systematic review and meta-analysis
Authors: Afrose Dinara , Chen Hao , Ranashinghe Amali , Liu Chia-chi , Henessy Annemarie , Hansbro Philip M. , McClements Lana
Published: June 2022

Background

Preeclampsia is a multifactorial cardiovascular disorder of pregnancy. If left untreated, it can lead to severe maternal and fetal outcomes. Hence, timely diagnosis and management of preeclampsia are extremely important. Biomarkers of oxidative stress are associated with the pathogenesis of preeclampsia and therefore could be indicative of evolving preeclampsia and utilized for timely diagnosis. In this study, we conducted a systematic review and meta-analysis to determine the most reliable oxidative stress biomarkers in preeclampsia, based on their diagnostic sensitivities and specificities as well as their positive and negative predictive values.

Methods

A systematic search using PubMed, ScienceDirect, ResearchGate, and PLOS databases (1900 to March 2021) identified nine relevant studies including a total of 343 women with preeclampsia and 354 normotensive controls.

Results

Ischemia-modified albumin (IMA), uric acid (UA), and malondialdehyde (MDA) were associated with 3.38 (95% CI 2.23, 4.53), 3.05 (95% CI 2.39, 3.71), and 2.37 (95% CI 1.03, 3.70) odds ratios for preeclampsia diagnosis, respectively. The IMA showed the most promising diagnostic potential with the positive predictive ratio (PPV) of 0.852 (95% CI 0.728, 0.929) and negative predictive ratio (NPV) of 0.811 (95% CI 0.683, 0.890) for preeclampsia. Minor between-study heterogeneity was reported for these biomarkers (Higgins’ I2 = 0–15.879%).

Conclusions

This systematic review and meta-analysis identified IMA, UA, and MDA as the most promising oxidative stress biomarkers associated with established preeclampsia. IMA as a biomarker of tissue damage exhibited the best diagnostic test accuracy. Thus, these oxidative stress biomarkers should be further explored in larger cohorts for preeclampsia diagnosis.

Graphical Abstract
Major mistakes and errors in the use of Trial Sequential Analysis in systematic reviews or meta-analyses – protocol for a systematic review
Authors: Riberholt Christian Gunge , Olsen Markus Harboe , Milan Joachim Birch , Gluud Christian
Published: June 2022

Background

Adequately conducted systematic reviews with meta-analyses are considered the highest level of evidence and thus directly defines many clinical guidelines. However, the risks of type I and II errors in meta-analyses are substantial. Trial Sequential Analysis is a method for controlling these risks. Erroneous use of the method might lead to research waste or misleading conclusions.

Methods

The current protocol describes a systematic review aimed to identify common and major mistakes and errors in the use of Trial Sequential Analysis by evaluating published systematic reviews and meta-analyses that include this method. We plan to include all studies using Trial Sequential Analysis published from January 2018 to January 2022, an estimated 400 to 600 publications. We will search Medical Literature Analysis and Retrieval System Online and the Cochrane Database of Systematic Reviews, including studies with all types of participants, interventions, and outcomes. Two independent reviewers will screen titles and abstracts, include relevant full text articles, extract data from the studies into a predefined checklist, and evaluate the methodological quality of the study using the AMSTAR 2, assessing the methodological quality of the systematic reviews.

Discussion

This protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P). The identified mistakes and errors will be published in peer reviewed articles and form the basis of a reviewed guideline for the use of Trial Sequential Analysis. Appropriately controlling for type I and II errors might reduce research waste and improve quality and precision of the evidence that clinical guidelines are based upon.
R-convexity in R-vector spaces
Authors: Ebrahimi Meymand Ali , Alijani Azadeh
Published: June 2022

In this paper, for every relation R on a vector space V, we consider the R-vector space $(V,R)$
(
V
,
R
)
and define the notions of R-convexity, R-convex hull, and R-extreme point in this space. Some examples are provided to compare them with the reference cases. The effects of some operations on R-convex sets are investigated. In particular, it is shown that the R-interior of an R-convex set is also an R-convex set under some restrictions on R. Also, we give some equivalent conditions for R-extremeness. Moreover, the notions of R-convex and R-affine maps on R-vector spaces are defined, and some results that assert the relation between an R-convex map f and its R-epigraph under some limitations on R are considered. Several propositions, such as R-continuous maps preserve R-compact sets and R-affine maps preserve R-convex sets, are presented, and some results on the composition of R-convex and R-affine maps are considered. Finally, some applications of R-convexity are investigated in optimization. More precisely, we show that the extrema values of R-affine R-continuous maps are reached on R-extreme points. Moreover, local and global minimum points of an R-convex map f on R-convex set K are considered.
On some bounds on the perturbation of invariant subspaces of normal matrices with application to a graph connection problem
Authors: Bhattacharya Subhrajit
Published: June 2022

We provide upper bounds on the perturbation of invariant subspaces of normal matrices measured using a metric on the space of vector subspaces of $\mathbb{C}^{n}$

C
n

in terms of the spectrum of both unperturbed and perturbed matrices as well as the spectrum of the unperturbed matrix only. The results presented give tighter bounds than the Davis–Kahan sinΘ theorem. We apply the result to a graph perturbation problem.
Complex symmetric Toeplitz operators on the generalized derivative Hardy space
Authors: Ko Eungil , Lee Ji Eun , Lee Jongrak
Published: June 2022

The generalized derivative Hardy space $S^{2}_{\alpha ,\beta}(\mathbb{D})$

S

α
,
β

2

(
D
)
consists of all functions whose derivatives are in the Hardy and Bergman spaces as follows:

for positive integers α, β, $$ S^{2}_{\alpha ,\beta}(\mathbb{D})= \biggl\{ f\in H(\mathbb{D}) : \Vert {f} \Vert ^{2}_{S^{2}_{ \alpha ,\beta}}= \Vert {f} \Vert ^{2}_{H^{2}}+{ \frac{{\alpha +\beta}}{\alpha \beta}} \bigl\Vert {f'} \bigr\Vert ^{2}_{A^{2}}+ \frac{1}{\alpha \beta} \bigl\Vert {f'} \bigr\Vert ^{2}_{H^{2}}< \infty \biggr\} , $$

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,
β

2

(
D
)
=

{
f
∈
H
(
D
)
:

∥
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∥

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2

=

∥
f
∥

H
2

2

+

α
+
β

α
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∥

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′

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A
2

2

+

1

α
β

∥

f
′

∥

H
2

2

<
∞
}

,
where $H({\mathbb{D}})$
H
(
D
)
denotes the space of all functions analytic on the open unit disk ${\mathbb{D}}$
D
. In this paper, we study characterizations for Toeplitz operators to be complex symmetric on the generalized derivative Hardy space $S^{2}_{\alpha ,\beta}(\mathbb{D})$

S

α
,
β

2

(
D
)
with respect to some conjugations $C_{\xi}$

C
ξ

, $C_{\mu , \lambda}$

C

μ
,
λ

. Moreover, for any conjugation C, we consider the necessary and sufficient conditions for complex symmetric Toeplitz operators with the symbol φ of the form $\varphi (z)=\sum_{n=1}^{\infty}\overline{\hat{\varphi}(-n)} \overline{z}^{n}+\sum_{n=0}^{\infty}\hat{\varphi}(n)z^{n}$
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(
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)
=

∑

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=
1

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ˆ

(
−
n
)

‾

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n

+

∑

n
=
0

∞

φ
ˆ

(
n
)

z
n

. Next, we also study complex symmetric Toeplitz operators with non-harmonic symbols on the generalized derivative Hardy space $S^{2}_{\alpha ,\beta}(\mathbb{D})$

S

α
,
β

2

(
D
)
.
Post COVID-19 condition and its physical, mental and social implications: protocol of a 2-year longitudinal cohort study in the Belgian adult population
Authors: Smith Pierre , Proesmans Kristiaan , Van Cauteren Dieter , Demarest Stefaan , Drieskens Sabine , De Pauw Robby , Cornelissen Laura , De Ridder Karin , Charafeddine Rana
Published: June 2022

Background

Since the onset of the COVID-19 pandemic, most research has focused on the pathophysiology and management of the acute symptoms of COVID-19, yet some people tend to experience symptoms beyond the acute phase of infection, that is, Post COVID-19 condition (PCC). However, evidence on the long-term health impacts of a COVID-19 infection are still scarce. The purpose of this paper is to describe the COVIMPACT study, which aims to set up a cohort of people who have been tested positive for COVID-19 and study the evolution of their physical, mental and social health over the medium (3 months) and long term (two years), and the factors associated with an (un)favorable evolution.

Methods

COVIMPACT is a longitudinal cohort study organised over a two-years period between April 2021 and April 2023. The eligible population is all people aged 18 years and older, living in Belgium, with a recent COVID-19 infection and contacted by the health authorities for contact tracing. Two questionnaires are used: a baseline questionnaire that aims to assess the initial health status of the participants and their status during the acute phase of the illness, and a follow-up questionnaire that is sent every three months after participants enter into the cohort. A matched non-COVID-19 control group was also selected. As of November 1, 2021, 10,708 people completed the baseline questionnaire (5% of the eligible population) and the follow-up participation rate was 79%. In total, 48% of the cohort participants appeared to fit the proposed case definition of PCC (i.e. report at least one symptom related to their COVID-19 infection three months afterwards).

Discussion

This study was designed to provide timely information on the short and long term impact of a COVID-19 infection, to stakeholders such as policymakers, health practitioners and people with PCC. Although the follow-up participation rate was good (79%), the participation rate of the eligible population was low (5%). Compared to other studies, this study has a large sample, of non-hospitalised and hospitalised people, who will be followed over a long period of 3 months to two years post infection, and with a global approach to their health.
The free flap based on a single proximal perforator of the radial artery: ultrasonography study and clinical applications in reconstruction of soft tissue defects in finger
Authors: Wu Guangzhi , Zhang Zhan , Zhang Fan , Zhang Yiqun , Wang Qianqian , Yu Wei
Published: June 2022

Objectives

To locate an anastomosable constant perforator of the radial artery on the proximal forearm using ultrasonography and describe the application of a free radial artery flap based on a single proximal perforator for the reconstruction of soft tissue defects in finger.

Methods

In 20 forearms (ten right and ten left) from ten volunteers, the perforators in the proximal half of the forearm from the radial artery were visualized using ultrasonography. The free radial artery perforator flaps based on the single perforator were used to reconstruct digital soft tissue defects in four cases between October 2017 and May 2018.

Results

Of the 20 forearms, an anastomosable perforator was consistently detected in the radial artery in the forearm’s proximal half. The perforator diameter was 0.7 ± 0.1 mm, and the pedicle length was 12 ± 3 mm according to ultrasonography. The perforator’s location was far from the elbow crease (8.8 ± 1.4 cm), and the relative distance of the perforator’s location from the elbow crease to the wrist crease was 37.2% ± 4.8%. In clinical cases, all flaps survived. Flap size ranged from 3.5 to 6.5 cm in length and 2.3–3.0 cm in width. Donor sites of the forearm were closed primarily in all cases. During a mean period of 12 months (8–14 months) follow-up, the average static 2-PD was 13.8 mm (10–18 mm) in the flap area, and the ROM of DIP was 35° (30–40°), PIP was 82° (45–110°), and MP was 85° (70–90°) of the affected finger. The mean Brief Michigan Hand Questionnaire (BMHQ) score was 72.9 (60.4–85.4) in the affected hand.

Conclusions

An anastomosable perforator is consistently located on the radial artery in the proximal half of the forearm. The free radial artery flap based on this single perforator provides acceptable functional and cosmetic outcomes for reconstructing digital soft tissue defects. With the preservation of the forearm’s main vessel (radial artery), this flap provides another reliable option for hand surgeons to reconstruct small soft tissue defects in finger.
Tauroursodeoxycholic acid: a potential therapeutic tool in neurodegenerative diseases
Authors: Khalaf Kareem , Tornese Paolo , Cocco Antoniangela , Albanese Alberto
Published: June 2022

Most neurodegenerative disorders are diseases of protein homeostasis, with misfolded aggregates accumulating. The neurodegenerative process is mediated by numerous metabolic pathways, most of which lead to apoptosis. In recent years, hydrophilic bile acids, particularly tauroursodeoxycholic acid (TUDCA), have shown important anti-apoptotic and neuroprotective activities, with numerous experimental and clinical evidence suggesting their possible therapeutic use as disease-modifiers in neurodegenerative diseases. Experimental evidence on the mechanisms underlying TUDCA’s neuroprotective action derives from animal models of Alzheimer’s disease, Parkinson’s disease, Huntington’s diseases, amyotrophic lateral sclerosis (ALS) and cerebral ischemia. Preclinical studies indicate that TUDCA exerts its effects not only by regulating and inhibiting the apoptotic cascade, but also by reducing oxidative stress, protecting the mitochondria, producing an anti-neuroinflammatory action, and acting as a chemical chaperone to maintain the stability and correct folding of proteins. Furthermore, data from phase II clinical trials have shown TUDCA to be safe and a potential disease-modifier in ALS. ALS is the first neurodegenerative disease being treated with hydrophilic bile acids. While further clinical evidence is being accumulated for the other diseases, TUDCA stands as a promising treatment for neurodegenerative diseases.
Predicting handgrip power of young adult population among major ethnic groups of Sabah: a multivariate analysis
Authors: Hossain Parash M Tanveer , Khazri Hasanur Bin , Mustapha Zainal Arifin , Shimmi Sadia Choudhury
Published: June 2022

Background

Handgrip power is an essential indicator of health, vital for grasping or gripping sports, and crucial for providing information related to work capacity. The present study investigated any linear relationship of handgrip power with hand anthropometric variables (hand length, handbreadth, middle finger length, second inter-crease length of the middle finger, and hand span), gender, and ethnicity in young adults of Sabah.

Methods

In this cross-sectional study (from January 2020 to December 2021), the adult Sabahan population (18-25 years) was stratified into four ethnicities (KadazanDusun, Bajau, Malay, and Chinese) and was further stratified as males and females. Then, 46 subjects were randomly selected from each gender, and the ethnic group met the intended sample size. The hand dimensions were measured using a digital calliper, and the handgrip power was measured using a portable dynamometer. The relationship between the response variable and explanatory variables was analyzed at first through simple linear regression and then multiple linear regression. R2, adjusted R2, and standard errors of the estimates were used to compare different models. Statistical analyses were performed using IBM SPSS Statistics 27 and StatCrunch.

Results

The study found a linear relationship between gender, height, hand length, handbreadth, hand span, middle finger length, and second inter-crease length of both hands with the corresponding hand’s grip power. The highest percentage (68% and 67%) of handgrip variability was demonstrated by the model predicting handgrip power for right-handed subjects, followed by the general models without stratifying based on hand dominance which was able to explain 63% and 64% of the variability of handgrip power. The study proposes the models for predicted right (RHGP) and left handgrip power (LHGP) of 18 to 25 years old adults from major ethnic groups of Sabah RHGP = − 18.972 − 8.704 Gender + 7.043 Right hand breadth and LHGP = − 11.621 − 9.389 Gender + 5.861 Left hand breadth respectively.

Conclusion

The predicted handgrip power would be a key to selecting a better player or a better worker or assessing the prognosis of a disease or the wellbeing of a person. The study can be further expanded to all ethnicities and ages of people of Sabah or even Malaysia.
Different dietary starch patterns in low-protein diets: effect on nitrogen efficiency, nutrient metabolism, and intestinal flora in growing pigs
Authors: Zhou Junyan , Wang Lu , Yang Lijie , Yang Guangxin , Zeng Xiangfang , Qiao Shiyan
Published: June 2022

Background

Protein releases amino acids faster than starch releases glucose in digestive tract of pigs fed low-protein (LP) diets. Poor synchronization of dietary glucose and amino acids supply leads to compromised nitrogen efficiency. Dietary starch patterns modulation may improve this situation.

Methods

Growing barrows (29.7 ± 2.0 kg) were randomly allotted into 5 dietary treatments with LP diets consisting of different purified starches. Treatments included: waxy corn starch (W LP), corn starch + waxy corn starch (C + W LP), corn starch (C LP), pea starch + waxy corn starch (P + W LP) and pea starch (P LP). In the experiment, growth performance, protein deposition, nutrient metabolism, and fecal microbial community of pigs were investigated. In vitro starch digestion was used for predicting the in vivo glucose response.

Results

Dietary starch in vitro glucose release profile was determined by starch source and the ratio of amylopectin and amylose. C + W LP treatment showed decreased total nitrogen excretion and plasma citrulline concentration and improved plasma leptin concentration among treatments (P < 0.05). Besides, the highest nitrogen apparent biological value, whole-body protein deposition and growth performance and lowest urinary nitrogen excretion were also observed in C + W LP treatment. Compared with the other groups, C + W LP and C LP showed increased plasma pyruvate, IGF-1, and lipase concentrations (P < 0.05). The W LP group presented dramatically increased plasma alanine and urea nitrogen concentration and decreased aldolase and leptin concentrations (P < 0.05). Dietary starch patterns did not make an impact on bacterial richness and diversity, but changed the taxonomic and functional structures of the microbial communities. Microbial protein fermentation product (isobutyrate and isovalerate) presented increased in P LP treatments compared with the other treatments (P < 0.05).

Conclusions

Dietary starch patterns modulation can regulate dietary glucose release profile, nutrient metabolism, protein turnover, and fecal microbial fermentation in pigs. The optimal dietary glucose release profile effectively strengthened whole-body protein deposition and improve nitrogen efficiency and growth performance in growing pigs fed LP diets.
Ecogenomics sheds light on diverse lifestyle strategies in freshwater CPR
Authors: Chiriac Maria-Cecilia , Bulzu Paul-Adrian , Andrei Adrian-Stefan , Okazaki Yusuke , Nakano Shin-ichi , Haber Markus , Kavagutti Vinicius Silva , Layoun Paul , Ghai Rohit , Salcher Michaela M.
Published: June 2022

Background

The increased use of metagenomics and single-cell genomics led to the discovery of organisms from phyla with no cultivated representatives and proposed new microbial lineages such as the candidate phyla radiation (CPR or Patescibacteria). These bacteria have peculiar ribosomal structures, reduced metabolic capacities, small genome, and cell sizes, and a general host-associated lifestyle was proposed for the radiation. So far, most CPR genomes were obtained from groundwaters; however, their diversity, abundance, and role in surface freshwaters is largely unexplored. Here, we attempt to close these knowledge gaps by deep metagenomic sequencing of 119 samples of 17 different freshwater lakes located in Europe and Asia. Moreover, we applied Fluorescence in situ Hybridization followed by Catalyzed Reporter Deposition (CARD-FISH) for a first visualization of distinct CPR lineages in freshwater samples.

Results

A total of 174 dereplicated metagenome-assembled genomes (MAGs) of diverse CPR lineages were recovered from the investigated lakes, with a higher prevalence from hypolimnion samples (162 MAGs). They have reduced genomes (median size 1 Mbp) and were generally found in low abundances (0.02–14.36 coverage/Gb) and with estimated slow replication rates. The analysis of genomic traits and CARD-FISH results showed that the radiation is an eclectic group in terms of metabolic capabilities and potential lifestyles, ranging from what appear to be free-living lineages to host- or particle-associated groups. Although some complexes of the electron transport chain were present in the CPR MAGs, together with ion-pumping rhodopsins and heliorhodopsins, we believe that they most probably adopt a fermentative metabolism. Terminal oxidases might function in O2 scavenging, while heliorhodopsins could be involved in mitigation against oxidative stress.

Conclusions

A high diversity of CPR MAGs was recovered, and distinct CPR lineages did not seem to be limited to lakes with specific trophic states. Their reduced metabolic capacities resemble the ones described for genomes in groundwater and animal-associated samples, apart from Gracilibacteria that possesses more complete metabolic pathways. Even though this radiation is mostly host-associated, we also observed organisms from different clades (ABY1, Paceibacteria, Saccharimonadia) that appear to be unattached to any other organisms or were associated with ‘lake snow’ particles (ABY1, Gracilibacteria), suggesting a broad range of potential life-strategies in this phylum.
The Otolaryngology boot camp: A scoping review evaluating commonalities and appraisal for curriculum design and delivery
Authors: Bondzi-Simpson Adom , Lindo C. J. , Hoy Monica , Lui Justin T.
Published: June 2022

Objective

Surgical boot camps are becoming increasingly popular in Otolaryngology–Head and Neck Surgery (OHNS) residency programs. Despite pioneering virtual reality and simulation-based surgical education, these boot camps have lacked critical appraisal. The objective of this article was to examine the adoption and utility of surgical boot camps in OHNS residency training programs around the world.

Data Sources

Ovid Medline and PubMed databases were systematically searched in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for scoping reviews. Additionally, a grey literature search was performed.

Review Methods

Inclusion criteria were peer-reviewed publications and grey literature sources that reported on OHNS boot camps for the novice learner. The search was restricted to human studies published in English. Studies were excluded if they were not examining junior trainees.

Results

A total of 551 articles were identified. Following removal of duplicates, screening, and full text review, 16 articles were included for analysis. Seven major boot camps were identified across various academic sites in the world. Most boot camps were one-day intensive camps incorporating a mixture of didactic, skill specific, and simulation sessions using an array of task trainers and high-fidelity simulators focusing on OHNS emergencies. Studies measuring trainee outcomes demonstrated improvement in trainee confidence, immediate knowledge, and skill acquisition.

Conclusion

Surgical boot camps appear to be an effective tool for short term knowledge and skill acquisition. Further studies should examine retention of skill and maintenance of confidence over longer intervals, as little is known about these lasting effects.