bluuebunny/crossref_metadata_2025 huggingface dataset:
Generalized Kinematics Analysis of Hybrid Mechanisms Based on Screw Theory and Lie Groups Lie Algebras
Authors: Sun Peng , Li Yanbiao , Chen Ke , Zhu Wentao , Zhong Qi , Chen Bo
Published: October 2021

Advanced mathematical tools are used to conduct research on the kinematics analysis of hybrid mechanisms, and the generalized analysis method and concise kinematics transfer matrix are obtained. In this study, first, according to the kinematics analysis of serial mechanisms, the basic principles of Lie groups and Lie algebras are briefly explained in dealing with the spatial switching and differential operations of screw vectors. Then, based on the standard ideas of Lie operations, the method for kinematics analysis of parallel mechanisms is derived, and Jacobian matrix and Hessian matrix are formulated recursively and in a closed form. Then, according to the mapping relationship between the parallel joints and corresponding equivalent series joints, a forward kinematics analysis method and two inverse kinematics analysis methods of hybrid mechanisms are examined. A case study is performed to verify the calculated matrices wherein a humanoid hybrid robotic arm with a parallel-series-parallel configuration is considered as an example. The results of a simulation experiment indicate that the obtained formulas are exact and the proposed method for kinematics analysis of hybrid mechanisms is practically feasible.
A narrative review on the validity of electronic health record-based research in epidemiology
Authors: Gianfrancesco Milena A. , Goldstein Neal D.
Published: October 2021

Electronic health records (EHRs) are widely used in epidemiological research, but the validity of the results is dependent upon the assumptions made about the healthcare system, the patient, and the provider. In this review, we identify four overarching challenges in using EHR-based data for epidemiological analysis, with a particular emphasis on threats to validity. These challenges include representativeness of the EHR to a target population, the availability and interpretability of clinical and non-clinical data, and missing data at both the variable and observation levels. Each challenge reveals layers of assumptions that the epidemiologist is required to make, from the point of patient entry into the healthcare system, to the provider documenting the results of the clinical exam and follow-up of the patient longitudinally; all with the potential to bias the results of analysis of these data. Understanding the extent of as well as remediating potential biases requires a variety of methodological approaches, from traditional sensitivity analyses and validation studies, to newer techniques such as natural language processing. Beyond methods to address these challenges, it will remain crucial for epidemiologists to engage with clinicians and informaticians at their institutions to ensure data quality and accessibility by forming multidisciplinary teams around specific research projects.
Growth differentiation factor-15 and incident chronic kidney disease: a population-based cohort study
Authors: Bao Xue , Xu Biao , Borné Yan , Orho-Melander Marju , Melander Olle , Nilsson Jan , Christensson Anders , Engström Gunnar
Published: October 2021

Background

The relationship between growth differentiation factor 15 (GDF-15) and the development of chronic kidney disease (CKD) is still unclear. We sought to examine whether plasma GDF-15 was related to incident CKD and kidney function decline using a large prospective cohort study.

Methods

4318 participants of the Malmö Diet and Cancer Study-Cardiovascular Cohort were examined in 1991-1994. Incidence of CKD was followed prospectively by linkage with national patient registers. Estimated glomerular filtration rate (eGFR) was available for all participants at baseline, and was re-measured in a subgroup of 2744 subjects after 16.6 ± 1.49 years. Incidence of CKD was examined in relation to GDF-15 using Cox regression analysis. Logistic regression was used to examine the association of GDF-15 with eGFR change and eGFR-based CKD. Models were carefully corrected for potential confounders including baseline eGFR, N-terminal pro-B-type natriuretic peptide, and competing risk from death.

Results

165 patients developed CKD after 19.2 ± 4.04 years of follow-up. The adjusted hazard ratio (95% confidence interval, CI) for CKD in 4th versus 1st quartile of GDF-15 was 2.37 (1.33, 4.24) (p for trend < 0.01). Each per 1 standard deviation increase in GDF-15 was associated with a decline in eGFR of − 0.97 mL/min/1.73 m2 (95% CI, − 1.49 ~ − 0.45; p < 0.001). GDF-15 was also significantly associated eGFR-based CKD in 2713 subjects with baseline eGFR ≥60 mL/min/1.73 m2.

Conclusions

GDF-15 predicted incidence of CKD and eGFR decline in the general population, independent of a wide range of potential risk factors and competing risk of death.
Prospective association between depressive symptoms and stroke risk among middle-aged and older Chinese
Authors: Cui Yimin , Zhu Chunsu , Lian Zhiwei , Han Xueyan , Xiang Qian , Liu Zhenming , Zhou Ying
Published: October 2021

Background

This study aimed to assess the association between baseline symptoms and changes in depressive symptoms and stroke incidents.

Methods

We used data from the Chinese Health and Retirement Longitudinal Study conducted in 2013, 2015, and 2018. In total, 10,100 individuals aged ≥45 years and without a history of stroke in 2013 were included. Depressive symptoms were measured using the 10-item version of the Center for Epidemiological Studied Depression scale (elevated depressive symptoms cutoff ≥10). Changes of depressive symptoms were assessed by two successive surveys (stable low/no, recent onset, recently remitted, and stable high depressive symptoms). We assessed whether baseline depressive symptoms and changes of them were associated with stroke incidents reported through 2018. Logistic regression analyses adjusted for age, gender, education, marital status and other potential confounders were performed.

Results

For the analysis of baseline depressive symptoms and stroke (n = 10,100), 545 (5.4%) reported stroke incidents in the following 5-year period. Individuals with elevated depressive symptoms in 2013 experienced a markedly higher stroke risk (odds ratio (OR) = 1.53, 95% confidence interval (CI) = 1.28–1.84) compared with those without elevated depressive symptoms. In the analysis of changes in depressive symptoms (n = 8491, 430 (5.1%) stroke events), participants with stable high (OR = 2.01, 95% CI = 1.58–2.56) and recent-onset (OR = 1.39, 95% CI = 1.04–1.85) depressive symptoms presented higher stroke risk compared to those with stable low/no depressive symptoms, while recently remitted symptoms (OR = 1.12, 95% CI = 0.80–1.57) were not associated with stroke risk.

Conclusions

In conclusion, stable high and newly started depressive symptoms were associated with increased stroke risk, whereas the improvement of depressive symptoms was not related to increase in stroke risk, suggesting that stroke risk may be decreased by effective management of depressive symptoms.
The effect of two weeks of spinal manipulative therapy and home stretching exercises on pain and disability in patients with persistent or recurrent neck pain; a randomized controlled trial
Authors: Bakken Anders Galaasen , Eklund Andreas , Warnqvist Anna , O’Neill Søren , Axén Iben
Published: October 2021

Background

Recurrent or persistent neck pain affects a vast number of people globally, leading to reduced quality of life and high societal costs. Clinically, it is a difficult condition to manage, and treatment effect sizes are often moderate at best. Activity and manual therapy are first-line treatment options in current guidelines. We aimed to investigate the combination of home stretching exercises and spinal manipulative therapy in a multicentre randomized controlled clinical trial, carried out in multidiscipline ary primary care clinics.

Methods

The treatment modalities utilized were spinal manipulative therapy and home stretching exercises compared to home stretching exercises alone. Both groups received 4 treatments for 2 weeks. The primary outcome was pain, where the subjective pain experience was investigated by assessing pain intensity (NRS − 11) and the quality of pain (McGill Pain Questionnaire). Neck disability and health status were secondary outcomes, measured using the Neck Disability Indexthe EQ-5D, respectively. One hundred thirty-one adult subjects were randomized to one of the two treatment groups. All subjects had experienced persistent or recurrent neck pain the previous 6 months and were blinded to the other group intervention. The clinicians provided treatment for subjects in both group and could not be blinded. The researchers collecting data were blinded to treatment allocation, as was the statistician performing data analyses. An intention-to-treat analysis was used.

Results

Sixty-six subjects were randomized to the intervention group, and sixty-five to the control group. For NRS − 11, a B-coefficient of − 0,01 was seen, indication a 0,01 improvement for the intervention group in relation to the control group at each time point with a p-value of 0,305. There were no statistically significant differences between groups for any of the outcome measures.

Conclusion

Based on the current findings, there is no additional treatment effect from adding spinal manipulative therapy to neck stretching exercises over 2 weeks for patients with persistent or recurrent neck pain.

Trial registration

The trial was registered 03/07/2018 at ClinicalTrials.gov, registration number: NCT03576846.
Detection of xerostomia, Sicca, and Sjogren’s syndromes in a national sample of adults
Authors: Stankeviciene Indre , Puriene Alina , Mieliauskaite Diana , Stangvaltaite-Mouhat Lina , Aleksejuniene Jolanta
Published: October 2021

Objectives

To assess the prevalence and determinants of xerostomia among adults and identify how many of the ones experiencing xerostomia have Sicca and Sjogren's syndromes.

Materials and methods

This cross-sectional study included 1405 35–74-year-old Lithuanians (51.7% response rate) from the five largest Lithuanian cities and 10 peri-urban and rural areas that were randomly selected from each of the 10 Lithuanian counties. Xerostomia was determined by the self-reported experience of dry mouth as "often" or "always". A dentist diagnosed Sicca syndrome by unstimulated whole sialometry and the Schirmer's test, and all cases were referred to a rheumatologist to confirm Sjogren's syndrome. Self-reported questionnaires collected data about the determinants.

Results

The prevalence of xerostomia was 8.0% (n = 112), Sicca syndrome was diagnosed for 8 participants (0.60%), and Sjogren's syndrome for 2 participants (0.14%), with this being the first time it was diagnosed. Experiencing xerostomia was associated with older age (OR 1.7, 95% CI 1.1–2.6), urban residence (OR 3.3, 95% CI 1.6–5.0), presence of systemic diseases (OR 2.5, 95% CI 1.4–3.3), and the use of alcohol (OR 0.6, 95% CI 0.4–0.9). The higher proportion of participants with Sicca syndrome involved females, of older age, having systemic diseases, and using medications.

Conclusions

The prevalence of xerostomia was 8.0% and the determinants of xerostomia were older age, urban residence, systemic diseases, and absence of using alcohol. In total, 0.6% of participants had Sicca syndrome, which was more prevalent among females, older subjects, those with systematic diseases, and those using medications. Sjogren's syndrome was diagnosed in 0.14% of participants.

Clinical relevance

Dental clinicians need to be trained to identify potential Sjogren's syndrome cases.
Enhanced enzymatic production of cholesteryl 6ʹ-acylglucoside impairs lysosomal degradation for the intracellular survival of Helicobacter pylori
Authors: Muthusamy Sasikala , Jan Hau-Ming , Hsieh Ming-Yen , Mondal Soumik , Liu Wen-Chun , Ko Yi-An , Yang Wei-Yuan , Mong Kwok-Kong Tony , Chen Guang-Chao , Lin Chun-Hung
Published: October 2021

Background

During autophagy defense against invading microbes, certain lipid types are indispensable for generating specialized membrane-bound organelles. The lipid composition of autophagosomes remains obscure, as does the issue of how specific lipids and lipid-associated enzymes participate in autophagosome formation and maturation. Helicobacter pylori is auxotrophic for cholesterol and converts cholesterol to cholesteryl glucoside derivatives, including cholesteryl 6ʹ-O-acyl-α-d-glucoside (CAG). We investigated how CAG and its biosynthetic acyltransferase assist H. pylori to escape host-cell autophagy.

Methods

We applied a metabolite-tagging method to obtain fluorophore-containing cholesteryl glucosides that were utilized to understand their intracellular locations. H. pylori 26695 and a cholesteryl glucosyltransferase (CGT)-deletion mutant (ΔCGT) were used as the standard strain and the negative control that contains no cholesterol-derived metabolites, respectively. Bacterial internalization and several autophagy-related assays were conducted to unravel the possible mechanism that H. pylori develops to hijack the host-cell autophagy response. Subcellular fractions of H. pylori-infected AGS cells were obtained and measured for the acyltransferase activity.

Results

The imaging studies of fluorophore-labeled cholesteryl glucosides pinpointed their intracellular localization in AGS cells. The result indicated that CAG enhances the internalization of H. pylori in AGS cells. Particularly, CAG, instead of CG and CPG, is able to augment the autophagy response induced by H. pylori. How CAG participates in the autophagy process is multifaceted. CAG was found to intervene in the degradation of autophagosomes and reduce lysosomal biogenesis, supporting the idea that intracellular H. pylori is harbored by autophago-lysosomes in favor of the bacterial survival. Furthermore, we performed the enzyme activity assay of subcellular fractions of H. pylori-infected AGS cells. The analysis showed that the acyltransferase is mainly distributed in autophago-lysosomal compartments.

Conclusions

Our results support the idea that the acyltransferase is mainly distributed in the subcellular compartment consisting of autophagosomes, late endosomes, and lysosomes, in which the acidic environment is beneficial for the maximal acyltransferase activity. The resulting elevated level of CAG can facilitate bacterial internalization, interfere with the autophagy flux, and causes reduced lysosomal biogenesis.
Using the Rasch measurement theory to assess the psychometric properties of the Hopkins Symptom Checklist-10 in adolescents
Authors: Finbråten Hanne Søberg , Kleppang Annette Løvheim , Steigen Anne Mari
Published: October 2021

Background

The Hopkins Symptom Checklist-10 (HSCL-10) is widely used to measure psychological distress in adolescents. To provide valid and reliable results and generate recommendations for practice and policies, instruments with sound psychometric properties are required. The purpose of this study is to use Rasch measurement theory to assess the psychometric properties of the HSCL-10 among adolescents aged 13–19.

Methods

In this cross-sectional study, 6445 adolescents responded to a web-based questionnaire. Data were collected from lower and upper secondary schools in Norway during 2018. The data were analysed using the partial credit parameterisation of the unidimensional Rasch model.

Results

HSCL-10 was found to be unidimensional and to have acceptable reliability. One pair of items showed response dependency. The targeting of the instrument could have been better. All items had ordered thresholds. Three items under-discriminated and three displayed differential item functioning regarding gender.

Conclusions

HSCL-10 has potential for measuring psychological distress in adolescents, though there is room for improvement. To further improve this instrument, some items should be rephrased.
Factors associated with viremia in people living with HIV on antiretroviral therapy in Guatemala
Authors: Ortíz Dean W. , Roberts-Sano Olivia , Marroquin Hugo E. , Larson Lindsey , Franco Katherine B. , Spec Andrej , Melendez Johanna R. , Pinzón Rodolfo , Samayoa Ana J. , Mejia-Chew Carlos , O´Halloran Jane A.
Published: October 2021

Introduction

Viral suppression prevents HIV transmission and disease progression, but socio-economic and clinical factors can hinder the goal of suppression. We evaluated factors associated with viral non suppression (VNS) and persistent viremia (PV) in people living with HIV (PLHIV) receiving antiretroviral therapy (ART) in Guatemala.

Methods

We conducted a cross sectional analysis using data from an ongoing cohort of PLHIV attending the largest HIV clinic in Guatemala. Univariable and multivariable analyses were conducted between PLHIV with viral suppression and detectable viremia. VNS was defined as most recent HIV RNA ≥ 200 copies/ml and PV as two consecutive HIV RNA ≥ 200 copies/ml.

Results

Of 664 participants, 13.3% had VNS and 7.1% had PV. In univariable analysis disaggregated by gender, low income, poor education, perceived difficulty attending healthcare, and alcohol use were associated with VNS in men while low CD4 at diagnosis, multiple prior ART regimens and treatment interruptions were significant in both genders. Multiple prior ART regimens (adjusted Odds Ratio (aOR) 2.82, [95% confidence interval (CI) 1.59, 4.99], p < 0.01), treatment interruptions (aOR 4.51, [95% CI 2.13, 9.58], p < 0.01), excessive alcohol consumption (aOR 2.56, [95% CI 1.18, 5.54], p < 0.05) perceived difficulty attending healthcare (aOR 2.07, [ 95% CI 1.25, 3.42], p < 0.01) and low CD4 at diagnosis (aOR 2.34, 95% [CI 1.30, 4.20], p < 0.01) were independently associated with VNS on multivariable regression.

Conclusions

We conclude that socio-economic and clinical factors influence viral suppression in our cohort and vary between men and women. Gender specific approaches are necessary to achieve the 90% suppression goal.
Adult-onset Still’s disease with multiple lymphadenopathy: a case report and literature review
Authors: Huang Zhonghua , Xu Hua , Min Qinqin , Li Zhenguo , Bi Jiaxin , Liu Lingyun , Liang Yingying
Published: October 2021

Background

Adult-onset Still’s disease (AOSD) often presents with systemic multiple lymphadenopathy. In addition to the common paracortical and mixed patterns in AOSD lymph node histopathological features, other morphological patterns include diffuse, necrotic, and follicular patterns. However, to date, there have been few reports on the histopathological description of AOSD lymph nodes.

Case presentation

An 18-year-old woman presented 2 months earlier with pain in her large joints with painless rash formation; bilateral posterior cervical lymph node, left supraclavicular lymph node, and left posterior axillary lymph node enlargement, and no tenderness. Left cervical lymph node resection was performed for pathological examination. The lymph node structure was basically preserved, and subcapsular and medullary sinus structures were observed. Many histiocytes in the sinus were observed, the cortical area was reduced, a few lymphoid follicles of different sizes were observed, and some atrophy and hyperplasia were noted. The lymphoid tissue in the paracortical region of the lymph node was diffusely proliferative and enlarged, mainly comprising histiocytes with abundant cytoplasm, immunoblasts and numerous lymphocytes with slightly irregular, small- to medium-sized nuclei. Nuclear karyorrhexis was easily observed, showing a few nuclear debris and the “starry sky” phenomenon, accompanied by abundantly branching high endothelial small vessels with few scattered plasma cells and eosinophil infiltration. Lymphoid follicle immunophenotype with reactive proliferative changes was observed. Approximately 40% of the cells in the paracortical region were positive for Ki-67, and the histiocytes expressed CD68, CD163, and some expressed S-100, with the absence of myeloperoxidase. The immunoblasts expressed CD30 and CD20, not ALK or CD15. Background small- to medium-sized T cells expressed CD2, CD3, CD5, CD7, CD4, and CD8; the number of CD8-positive T cells was slightly predominant, and a small number of T cells expressed granzyme B and T-cell intracellular antigen 1. The patient received a comprehensive medical treatment after the operation, and her condition was stable without progression at the 11-month follow-up evaluation.

Conclusions

The pathological features of AOSD lymphadenopathy raises the awareness of AOSD among pathologists and clinicians and aids in the diagnosis and differential diagnosis of AOSD lymphadenopathy from other reactive lymphadenopathies (lupus lymphadenitis, etc.) and lymphomas.
One year of laboratory-based COVID-19 surveillance system in Belgium: main indicators and performance of the laboratories (March 2020–21)
Authors: Meurisse Marjan , Lajot Adrien , Dupont Yves , Lesenfants Marie , Klamer Sofieke , Rebolledo Javiera , Lernout Tinne , Leroy Mathias , Capron Arnaud , Van Bussel Johan , Quoilin Sophie , Andre Emmanuel , Kehoe Kaat , Waumans Luc , Van Acker Jos , Vandenberg Olivier , Van den Wijngaert Sigi , Verdonck Ann , Cuypers Lize , Van Cauteren Dieter
Published: October 2021

Background

With the spread of coronavirus disease 2019 (COVID-19), an existing national laboratory-based surveillance system was adapted to daily monitor the epidemiological situation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the Belgium by following the number of confirmed SARS-CoV-2 infections, the number of performed tests and the positivity ratio. We present these main indicators of the surveillance over a one-year period as well as the impact of the performance of the laboratories, regarding speed of processing the samples and reporting results, for surveillance.

Methods

We describe the evolution of test capacity, testing strategy and the data collection methods during the first year of the epidemic in Belgium.

Results

Between the 1st of March 2020 and the 28th of February 2021, 9,487,470 tests and 773,078 COVID-19 laboratory confirmed cases were reported. Two epidemic waves occurred, with a peak in April and October 2020. The capacity and performance of the laboratories improved continuously during 2020 resulting in a high level performance. Since the end of November 2020 90 to 95% of the test results are reported at the latest the day after sampling was performed.

Conclusions

Thanks to the effort of all laboratories a performant exhaustive national laboratory-based surveillance system to monitor the epidemiological situation of SARS-CoV-2 was set up in Belgium in 2020. On top of expanding the number of laboratories performing diagnostics and significantly increasing the test capacity in Belgium, turnaround times between sampling and testing as well as reporting were optimized over the first year of this pandemic.
Multiomics landscape of the autosomal dominant osteopetrosis type II disease-specific induced pluripotent stem cells
Authors: Li Chunhong , Shangguan Yu , Zhu Peng , Dai Weier , Tang Donge , Ou Minglin , Dai Yong
Published: October 2021

Background

Autosomal dominant osteopetrosis type II (ADO2) is a genetically and phenotypically metabolic bone disease, caused by osteoclast abnormalities. The pathways dysregulated in ADO2 could lead to the defects in osteoclast formation and function. However, the mechanism remains elusive.

Materials and methods

To systematically explore the molecular characterization of ADO2, we performed a multi-omics profiling from the autosomal dominant osteopetrosis type II iPSCs (ADO2-iPSCs) and healthy normal control iPSCs (NC-iPSCs) using whole genome re-sequencing, DNA methylation and N6-methyladenosine (m6A) analysis in this study.

Results

Totally, we detected 7,095,817 single nucleotide polymorphisms (SNPs) and 1,179,573 insertion and deletions (InDels), 1,001,943 differentially methylated regions (DMRs) and 2984 differential m6A peaks, and the comprehensive multi-omics profile was generated from the two cells. Interestingly, the ISG15 m6A level in ADO2-iPSCs is higher than NC-iPSCs by IGV software, and the differentially expressed m6A-modified genes (DEMGs) were highly enriched in the osteoclast differentiation and p53 signaling pathway, which associated with the development of osteopetrosis. In addition, combining our previously published transcriptome and proteome datasets, we found that the change in DNA methylation levels correlates inversely with some gene expression levels.

Conclusion

Our results indicate that the global multi-omics landscape not only provides a high-quality data resource but also reveals a dynamic pattern of gene expression, and found that the pathogenesis of ADO2 may begin early in life.
Development, validation and clinical usefulness of a prognostic model for relapse in relapsing-remitting multiple sclerosis
Authors: Chalkou Konstantina , Steyerberg Ewout , Bossuyt Patrick , Subramaniam Suvitha , Benkert Pascal , Kuhle Jens , Disanto Giulio , Kappos Ludwig , Zecca Chiara , Egger Matthias , Salanti Georgia
Published: October 2021

Abstract

Background

Prognosis for the occurrence of relapses in individuals with relapsing-remitting multiple sclerosis (RRMS), the most common subtype of multiple sclerosis (MS), could support individualized decisions and disease management and could be helpful for efficiently selecting patients for future randomized clinical trials. There are only three previously published prognostic models on this, all of them with important methodological shortcomings.

Objectives

We aim to present the development, internal validation, and evaluation of the potential clinical benefit of a prognostic model for relapses for individuals with RRMS using real-world data.

Methods

We followed seven steps to develop and validate the prognostic model: (1) selection of prognostic factors via a review of the literature, (2) development of a generalized linear mixed-effects model in a Bayesian framework, (3) examination of sample size efficiency, (4) shrinkage of the coefficients, (5) dealing with missing data using multiple imputations, (6) internal validation of the model. Finally, we evaluated the potential clinical benefit of the developed prognostic model using decision curve analysis. For the development and the validation of our prognostic model, we followed the TRIPOD statement.

Results

We selected eight baseline prognostic factors: age, sex, prior MS treatment, months since last relapse, disease duration, number of prior relapses, expanded disability status scale (EDSS) score, and number of gadolinium-enhanced lesions. We also developed a web application that calculates an individual’s probability of relapsing within the next 2 years. The optimism-corrected c-statistic is 0.65 and the optimism-corrected calibration slope is 0.92. For threshold probabilities between 15 and 30%, the “treat based on the prognostic model” strategy leads to the highest net benefit and hence is considered the most clinically useful strategy.

Conclusions

The prognostic model we developed offers several advantages in comparison to previously published prognostic models on RRMS. Importantly, we assessed the potential clinical benefit to better quantify the clinical impact of the model. Our web application, once externally validated in the future, could be used by patients and doctors to calculate the individualized probability of relapsing within 2 years and to inform the management of their disease.
Stereotactic direct-coiling of aneurysms—a feasibility study
Authors: Patil Arun Angelo , Pandey Deepak Kumar , Kumar Sidhartha , Chand Ashis , Jacob Megha
Published: October 2021

Aim of the study

Endovascular coiling has gained worldwide acceptance in the management of intracranial aneurysms. However, not all aneurysms can be coiled. Direct aneurysm puncture with aneurysm thrombosis has been performed, using coils for extracranial aneurysms and iron filings for intracranial aneurysms. Therefore, the feasibility of stereotactic aneurysm coiling with direct aneurysm puncture using Nester-coils was studied in an in vitro model.

Methods and findings

Twenty-eight aneurysms measuring 9–21 mm in diameters (median 14 mm) were made using 0.1 mm vinyl film that was connected to a monometer with 73 cm of water column. Twenty-three aneurysms were coiled through direct puncture of the aneurysms using a stereotactic frame. Five were coiled using a hand-held probe carrier.

Statistical analysis of the data was conducted by data analysis feature of Microsoft Excel.

Findings

The study showed that needle puncture of the aneurysm and coiling of the aneurysm through the needle can be done with ease and without any significant fluid leak from the puncture site. It also shows that the coil will stay within the aneurysm without entering the neck. The study also shows that this method can be done using free-hand technique. Furthermore, it shows that the probe holder for the needle can also be used as an aneurysm stabilizer and as a tamponade.
Improving Guideline-Congruent Care for Chemotherapy-Induced Nausea and Vomiting Prophylaxis in Pediatric Oncology Patients
Authors: Diorio Caroline , Vardaro Julie , Wei Yahui , Mauro Jane , Croy Colleen , Oranges Katelyn E. , Flanagan Lindsay , Reilly Anne F. , Bailey L. Charles , Jubelirer Tracey , Elgarten Caitlin W. , Freedman Jason L.
Published: October 2021

PURPOSE:

Chemotherapy-induced nausea and vomiting (CINV) is a very common side effect of pediatric cancer therapy. High-quality, evidence-based, pediatric-specific guidelines for prophylaxis and treatment of CINV are available. At many centers, guideline-concordant care is uncommon. We formed a multidisciplinary quality improvement team to implement guideline-concordant care for CINV prophylaxis at our center. We present the results following the first year of our interventions.

METHODS:

We planned and implemented a multipronged approach in three key phases: (1) developing and publishing an acute CINV prophylaxis pathway, (2) education of providers, and (3) updating the computerized provider order entry system. We used iterative, sequential Plan-Do-Study-Act cycles and behavioral economic strategies to improve adherence to guideline-concordant CINV prophylaxis. We focused on aprepitant usage as a key area for improvement.

RESULTS:

At the beginning of the study period, < 50% of patients were receiving guideline-concordant CINV prophylaxis and < 15% of eligible patients were receiving aprepitant. After 1 year, more than 60% of patients were receiving guideline-concordant care and 50% of eligible patients were receiving aprepitant.

CONCLUSION:

We describe the development and implementation of a standardized pathway for prevention of acute CINV in pediatric oncology patients. With a multidisciplinary, multifaceted approach, we demonstrate significant improvements to guideline-congruent CINV prophylaxis.
Robustness improvements of scale-free networks against cascading breakdown
Authors: Lei Wen , Ma Shan , Ma Junfeng
Published: October 2021

In this paper, we propose several strategies for improving the robustness of scale-free networks against cascading breakdown. Firstly, we introduce a damage-based measure of complete breakdown ratio. Then we propose a customized analytic algorithm to characterize the robustness against cascading breakdown in scale-free networks, and apply the robustness analysis algorithm to scale-free networks with different network structures. In order to improve the robustness of scale-free networks, some strategies are suggested, such as protection of network critical components, rewiring the preferential neighboring edges and absorbing partial load from overloaded edges. Finally, numerical experiments are performed to illustrate the effectiveness of these strategies for improving the robustness against cascading breakdown in scale-free networks.
Evolutionary conservation of systemic and reversible amyloid aggregation
Authors: Lacroix Emma , Pereira Lionel , Yoo Byoungjoo , Coyle Krysta M. , Chandhok Sahil , Zapf Richard , Marijan Dane , Morin Ryan D. , Vlachos Stephanie , Harden Nicholas , Audas Timothy E.
Published: October 2021

In response to environmental stress, human cells have been shown to form reversible amyloid aggregates within the nucleus, termed amyloid bodies (A-bodies). These protective physiological structures share many of the biophysical characteristics associated with the pathological amyloids found in Alzheimer's and Parkinson's disease. Here, we show that A-bodies are evolutionarily conserved across the eukaryotic domain, with their detection in Drosophila melanogaster and Saccharomyces cerevisiae marking the first examples of these functional amyloids being induced outside of a cultured cell setting. The conditions triggering amyloidogenesis varied significantly among the species tested, with results indicating that A-body formation is a severe, but sublethal, stress response pathway that is tailored to the environmental norms of an organism. RNA-sequencing analyses demonstrate that the regulatory low-complexity long non-coding RNAs that drive A-body aggregation are both conserved and essential in human, mouse and chicken cells. Thus, the identification of these natural and reversible functional amyloids in a variety of evolutionarily diverse species highlights the physiological significance of this protein conformation, and will be informative in advancing our understanding of both functional and pathological amyloid aggregation events.

This article has an associated First Person interview with the first author of the paper.
Evoked auditory potentials from African mole-rats and coruros reveal disparity in subterranean rodent hearing
Authors: Caspar Kai R. , Heinrich Alexandra , Mellinghaus Lea , Gerhardt Patricia , Begall Sabine
Published: October 2021

Hearing in subterranean rodents exhibits numerous peculiarities, including low sensitivity and restriction to a narrow range of comparatively low frequencies. Past studies provided two conflicting hypotheses explaining how these derived traits evolved: structural degeneration and adaptive specialization. To further elucidate this issue, we recorded auditory brainstem responses from three species of social subterranean rodents that differ in the degree of specialization to the underground habitat: the naked mole-rat (Heterocephalus glaber) and the Mashona mole-rat (Fukomys darlingi), which represent the ancient lineage of African mole-rats (Bathyergidae), and the coruro (Spalacopus cyanus), a South American rodent (Octodontidae) that adopted a subterranean lifestyle in more recent geological time. Additionally, we measured call amplitudes of social vocalizations to study auditory vocal coupling. We found elevated auditory thresholds and severe hearing range restrictions in the African mole-rats, with hearing in naked mole-rats tending to be more sensitive than in Mashona mole-rats, in which hearing notably deteriorated with increasing age. In contrast, hearing in coruros was similar to that of epigeic rodents, with its range extending into ultrasonic frequencies. However, as in the mole-rats, the coruros’ region of best hearing was located at low frequencies close to 1 kHz. We argue that the auditory sensitivity of African mole-rats, although remarkably poor, has been underestimated by recent studies, whereas data on coruros conform to previous results. Considering the available evidence, we propose to be open to both degenerative and adaptive interpretations of hearing physiology in subterranean mammals, as each may provide convincing explanations for specific auditory traits observed.
Effect of metformin on 18F-fluorodeoxyglucose uptake and positron emission tomographic imaging
Authors: Zhang Xieyi , Ogihara Takuo , Zhu Min , Gantumur Dolgormaa , Li Yang , Mizoi Kenta , Kamioka Hiroki , Tsushima Yoshito
Published: October 2021

Metformin is widely used to treat diabetes, but induces changes in glucose uptake in both normal organs and tumors. Here, we review the effects of metformin on the uptake of 1  8F-fludeoxyglucose (18F-FDG) in tissues and tumors, and its influence on 18F-FDG positron emission tomographic imaging (18F-FDG PET), as well as the mechanisms involved. This is an important issue, because metformin has diverse effects on tissue uptake of 18F-FDG, and this can affect the quality and interpretation of PET images. Metformin increases glucose uptake in the gastrointestinal tract, cerebral white matter, and the kidney, while regions of the cerebrum associated with memory show decreased glucose uptake, and the myocardium shows no change. Hepatocellular carcinoma and breast cancer show increased glucose uptake after metformin administration, while thyroid cancer shows decreased uptake, and colon and pancreatic cancers show no change. A high-energy diet increases 18F-FDG uptake, but this effect is blocked by metformin. Withdrawal of metformin 48 h before PET image acquisition is widely recommended. However, based on our review of the literature, we propose that the differentiation of metformin discontinuation could be reasonable. But future clinical trials are still needed to support our viewpoint.
3 T: the good, the bad and the ugly
Authors: Graves Martin John
Published: October 2021

It is around 20 years since the first commercial 3 T MRI systems became available. The theoretical promise of twice the signal-to-noise ratio of a 1.5 T system together with a greater sensitivity to magnetic susceptibility-related contrast mechanisms, such as the blood oxygen level dependent effect that is the basis for functional MRI, drove the initial market in neuroradiology. However, the limitations of the increased field strength soon became apparent, including the increased radiofrequency power deposition, tissue-dependent changes in relaxation times, increased artifacts, and greater safety concerns. Many of these issues are dependent upon MR physics and workarounds have had to be developed to try and mitigate their effects. This article reviews the underlying principles of the good, the bad and the ugly aspects of 3 T, discusses some of the methods used to improve image quality and explains the remaining challenges and concerns.
How to connect academics around the globe by organizing an asynchronous virtual unconference
Authors: Holman Constance , Kent Brianne A. , Weissgerber Tracey L.
Published: October 2021

Many conferences and in-person meetings have transitioned to virtual platforms in response to the COVID-19 pandemic. Here, we share strategies and lessons learned from organizing an international virtual unconventional conference, or ‘unconference’. The event focused on how early career researchers can advocate for systemic improvements in scientific publishing and research culture. The virtual unconference had three main components: (1) a virtual networking event, (2) asynchronous virtual brainstorming, and (3) a virtual open space, where participants could join or lead in-depth discussions. The unconference format was participant-driven and encouraged dialogue and collaboration between 54 attendees from 20 countries on six continents. Virtual brainstorming allowed participants to contribute to discussions at times that were convenient for them. Activity was consistently high throughout the 48 hours of virtual brainstorming and continued into the next day. The results of these discussions are collaboratively summarized in a paper entitled Empowering Early Career Researchers to Improve Science, co-authored by the unconference participants. We hope that this method report will help others to organize asynchronous virtual unconferences, while also providing new strategies for participant-driven activities that could be integrated into conventional virtual conferences.
Genome-wide association study of susceptibility to hospitalised respiratory infections
Authors: Williams Alexander T. , Shrine Nick , Naghra-van Gijzel Hardeep , Betts Joanna C. , Hessel Edith M. , John Catherine , Packer Richard , Reeve Nicola F. , Yeo Astrid J. , Abner Erik , Åsvold Bjørn Olav , Auvinen Juha , Bartz Traci M. , Bradford Yuki , Brumpton Ben , Campbell Archie , Cho Michael H. , Chu Su , Crosslin David R. , Feng QiPing , Esko Tõnu , Gharib Sina A. , Hayward Caroline , Hebbring Scott , Hveem Kristian , Jarvelin Marjo-Riitta , Jarvik Gail P. , Landis Sarah H. , Larson Eric B. , Liu Jiangyuan , Loos Ruth J.F. , Luo Yuan , Moscati Arden , Mullerova Hana , Namjou Bahram , Porteous David J. , Quint Jennifer K. ,   Regeneron Genomics Center, Ritchie Marylyn D. , Sliz Eeva , Stanaway Ian B. , Thomas Laurent , Wilson James F. , Hall Ian P. , Wain Louise V. , Michalovich David , Tobin Martin D.
Published: October 2021

Background: Globally, respiratory infections contribute to significant morbidity and mortality. However, genetic determinants of respiratory infections are understudied and remain poorly understood.

Methods: We conducted a genome-wide association study in 19,459 hospitalised respiratory infection cases and 101,438 controls from UK Biobank. We followed-up well-imputed top signals from the UK Biobank discovery analysis in 50,912 respiratory infection cases and 150,442 controls from 11 cohorts. We aggregated effect estimates across studies using inverse variance-weighted meta-analyses. Additionally, we investigated the function of the top signals in order to gain understanding of the underlying biological mechanisms.

Results: In the discovery analysis, we report 56 signals at P<5×10-6, one of which was genome-wide significant (P<5×10-8). The genome-wide significant signal was in an intron of PBX3, a gene that encodes pre-B-cell leukaemia transcription factor 3, a homeodomain-containing transcription factor. Further, the genome-wide significant signal was found to colocalise with gene-specific expression quantitative trait loci (eQTLs) affecting expression of PBX3 in lung tissue, where the respiratory infection risk alleles were associated with decreased PBX3 expression in lung tissue, highlighting a possible biological mechanism. Of the 56 signals, 40 were well-imputed in UK Biobank and were investigated in the 11 follow-up cohorts. None of the 40 signals replicated, with effect estimates attenuated.

Conclusions: Our discovery analysis implicated PBX3 as a candidate causal gene and suggests a possible role of transcription factor binding activity in respiratory infection susceptibility. However, the PBX3 signal, and the other well-imputed signals, did not replicate when aggregating effect estimates across 11 independent cohorts. Significant phenotypic heterogeneity and differences in study ascertainment may have contributed to this lack of statistical replication. Overall, our study highlighted putative associations and possible biological mechanisms that may provide insight into respiratory infection susceptibility.
ЭКОЛОГО-ЭКОНОМИЧЕСКАЯ ЭФФЕКТИВНОСТЬ ЗАЩИТНОГО ЛЕСОРАЗВЕДЕНИЯ В АРИДНОЙ ЗОНЕ
Authors: Suchkov Dmitry K.
Published: October 2021

Статья посвящена актуализации проблемы развития и повышения экономической эффективности работ по защитному лесоразведению.
Цель исследования – разработать предложения к технологии повышения эффективности защитного лесоразведения в засушливых районах России.
Материалы и методы. Для описания видового состава, их состояния и экономической эффективности, использовались методы оценки и прогнозирования состояния насаждений по Е.Г. Мозолевской и методы лесной таксации О.И. Бабошко. Основой для расчета затрат на 1 га ветроломных и стокорегулирующих лесных полос служили действующие расчетно-технологические карты на работы по защитному лесоразведению. Для перехода в современные цены использовали индексы изменения сметной стоимости строительно-монтажных работ.
Результаты. В работе приводятся оптимальные биоинженерные параметры систем ветроломных и стокорегулирующих лесных полос применительно к разным природным зонам Юга России, уровню эрозионной опасности и состоянию почвенного покрова склоновых земель, размеры и биогеографические закономерности динамики затрат на их создание. Представлен ассортимент деревьев и кустарников, используемых для защитного лесоразведения в засушливых регионах на основе анализа гидрофизических и гидрохимических свойств древесных пород позволяющий повысить биологическую устойчивость насаждений, увеличить срок их жизни, а значит и более полно выполнять свои защитные функции.
Заключение. Установлено, что в дефляционно-опасных районах капиталоемкость обустройства пашни системой ветроломных лесных полос находится в строгой зависимости от качества почвенно-климатических условий (природной зоны), выбранного уровня защитной лесистости и биоинженерных особенностей насаждений. В эрозионно-опасных районах капиталовложения в создание систем стокорегулирующих лесных полос на пашне обусловлены главным образом уклоном местности и степенью смытости почв.
Использование приведенных расчетов и закономерностей позволит повысить экономическую обоснованность капитальных вложений при планировании и проектировании лесомелиоративных мероприятий на пахотных землях проблемных регионов юга России.
ВЛИЯНИЕ ПИЩЕВОГО ПОВЕДЕНИЯ, РАСПРЕДЕЛЕНИЯ ЖИРА И ФИЗИЧЕСКОЙ АКТИВНОСТИ НА СИМПТОМЫ ФУНКЦИОНАЛЬНЫХ ГАСТРОИНТЕСТИНАЛЬНЫХ РАССТРОЙСТВ
Authors: Shklyaev Aleksey E. , Grigorieva Olga A. , Merzlyakova Yulia S. , Maksimov Kirill V. , Kazarin Daniil D.
Published: October 2021

Обоснование. Функциональные заболевания желудочно-кишечного тракта являются актуальной проблемой современной гастроэнтерологии в связи с ростом их частоты и значительным влиянием на качество жизни пациентов. В числе факторов, способствующих их манифестации, рассматриваются особенности образа жизни и питания. Однако, влияние нарушений пищевого поведения и распределения жировой ткани на выраженность гастроэнтерологической симптоматики у лиц с разным уровнем физической активности требует уточнения.

Цель: уточнить влияние пищевого поведения, распределения жира и физической активности на симптомы функциональных гастроинтестинальных расстройств.

Материалы и методы. Обследовано 60 человек без органических заболеваний желудочно-кишечного тракта в возрасте 22,7±0,19 года. Сформированы 2 группы по 30 человек: регулярно занимающиеся физическими упражнениями и не занимающиеся физическими упражнениями. Проведено анкетирование по опросникам GSRS, DEBQ, определены антропометрические данные. Статистическая обработка включала вычисление средних величин, их ошибок, t-критерий Стьюдента, критерий корреляции Пирсона, факторный анализ.

Результаты. Регулярно занимающиеся физическими упражнениями имеют более низкие показатели количества подкожной и висцеральной жировой ткани, чем не занимающиеся. В группе физически активных выявлено наличие обратной зависимости между синдромом запоров и количеством висцерального жира. У не занимающихся физическими упражнениями обнаружена прямая зависимость между количеством висцерального жира и рефлюкс-синдромом, экстернальным типом пищевого поведения. В фактор «риск гастроэнтерологической патологии» вошли: общий балл по опроснику GSRS, эмоциогенный и экстернальный типы пищевого поведения, окружность бедер и соотношение объем талии/объем бедер.

Заключение. Для минимизации симптомов функциональных гастроинтестинальных расстройств необходимо оптимальное количество висцерального жира, его уменьшение усугубляет синдром запоров, а увеличение – рефлюкс-синдром. Регулярные физические упражнения позволяют сбалансировать особенности пищевого поведения и оптимизировать количество жировой ткани в организме.