bluuebunny/crossref_metadata_2025 huggingface dataset:
Higher-order immunoglobulin repertoire restrictions in CLL: the illustrative case of stereotyped subsets 2 and 169
Authors: Gemenetzi Katerina , Psomopoulos Fotis , Carriles Alejandra A. , Gounari Maria , Minici Claudia , Plevova Karla , Sutton Lesley-Ann , Tsagiopoulou Maria , Baliakas Panagiotis , Pasentsis Kostas , Anagnostopoulos Achilles , Sandaltzopoulos Raphael , Rosenquist Richard , Davi Frederic , Pospisilova Sarka , Ghia Paolo , Stamatopoulos Kostas , Degano Massimo , Chatzidimitriou Anastasia
Published: October 2020

Chronic lymphocytic leukemia (CLL) major stereotyped subset 2 (IGHV3-21/IGLV3-21, ∼2.5% of all cases of CLL) is an aggressive disease variant, irrespective of the somatic hypermutation (SHM) status of the clonotypic IGHV gene. Minor stereotyped subset 169 (IGHV3-48/IGLV3-21, ∼0.2% of all cases of CLL) is related to subset 2, as it displays a highly similar variable antigen-binding site. We further explored this relationship through next-generation sequencing and crystallographic analysis of the clonotypic B-cell receptor immunoglobulin. Branching evolution of the predominant clonotype through intraclonal diversification in the context of ongoing SHM was evident in both heavy and light chain genes of both subsets. Molecular similarities between the 2 subsets were highlighted by the finding of shared SHMs within both the heavy and light chain genes in all analyzed cases at either the clonal or subclonal level. Particularly noteworthy in this respect was a ubiquitous SHM at the linker region between the variable and the constant domain of the IGLV3-21 light chains, previously reported as critical for immunoglobulin homotypic interactions underlying cell-autonomous signaling capacity. Notably, crystallographic analysis revealed that the IGLV3-21–bearing CLL subset 169 immunoglobulin retains the same geometry and contact residues for the homotypic intermolecular interaction observed in subset 2, including the SHM at the linker region, and, from a molecular standpoint, belong to a common structural mode of autologous recognition. Collectively, our findings document that stereotyped subsets 2 and 169 are very closely related, displaying shared immunoglobulin features that can be explained only in the context of shared functional selection.
Tumor burden, inflammation, and product attributes determine outcomes of axicabtagene ciloleucel in large B-cell lymphoma
Authors: Locke Frederick L. , Rossi John M. , Neelapu Sattva S. , Jacobson Caron A. , Miklos David B. , Ghobadi Armin , Oluwole Olalekan O. , Reagan Patrick M. , Lekakis Lazaros J. , Lin Yi , Sherman Marika , Better Marc , Go William Y. , Wiezorek Jeffrey S. , Xue Allen , Bot Adrian
Published: October 2020

ZUMA-1 demonstrated a high rate of durable response and a manageable safety profile with axicabtagene ciloleucel (axi-cel), an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, in patients with refractory large B-cell lymphoma. As previously reported, prespecified clinical covariates for secondary end point analysis were not clearly predictive of efficacy; these included Eastern Cooperative Oncology Group performance status (0 vs 1), age, disease subtype, disease stage, and International Prognostic Index score. We interrogated covariates included in the statistical analysis plan and an extensive panel of biomarkers according to an expanded translational biomarker plan. Univariable and multivariable analyses indicated that rapid CAR T-cell expansion commensurate with pretreatment tumor burden (influenced by product T-cell fitness), the number of CD8 and CCR7+CD45RA+ T cells infused, and host systemic inflammation, were the most significant determining factors for durable response. Key parameters differentially associated with clinical efficacy and toxicities, with both theoretical and practical implications for optimizing CAR T-cell therapy. This trial was registered at www.clinicaltrials.gov as #NCT02348216.
State-of-art review of traffic signal control methods: challenges and opportunities
Authors: Qadri Syed Shah Sultan Mohiuddin , Gökçe Mahmut Ali , Öner Erdinç
Published: October 2020

Introduction

Due to the menacing increase in the number of vehicles on a daily basis, abating road congestion is becoming a key challenge these years. To cope-up with the prevailing traffic scenarios and to meet the ever-increasing demand for traffic, the urban transportation system needs effective solution methodologies. Changes made in the urban infrastructure will take years, sometimes may not even be feasible. For this reason, traffic signal timing (TST) optimization is one of the fastest and most economical ways to curtail congestion at the intersections and improve traffic flow in the urban network.

Purpose

Researchers have been working on using a variety of approaches along with the exploitation of technology to improve TST. This article is intended to analyze the recent literature published between January 2015 and January 2020 for the computational intelligence (CI) based simulation approaches and CI-based approaches for optimizing TST and Traffic Signal Control (TSC) systems, provide insights, research gaps and possible directions for future work for researchers interested in the field.

Methods

In analyzing the complex dynamic behavior of traffic streams, simulation tools have a prominent place. Nowadays, microsimulation tools are frequently used in TST related researches. For this reason, a critical review of some of the widely used microsimulation packages is provided in this paper.

Conclusion

Our review also shows that approximately 77% of the papers included, utilizes a microsimulation tool in some form. Therefore, it seems useful to include a review, categorization, and comparison of the most commonly used microsimulation tools for future work. We conclude by providing insights into the future of research in these areas.
Raman2imzML converts Raman imaging data into the standard mass spectrometry imaging format
Authors: Iakab Stefania Alexandra , Sementé Lluc , García-Altares María , Correig Xavier , Ràfols Pere
Published: October 2020

Background

Multimodal imaging that combines mass spectrometry imaging (MSI) with Raman imaging is a rapidly developing multidisciplinary analytical method used by a growing number of research groups. Computational tools that can visualize and aid the analysis of datasets by both techniques are in demand.

Results

Raman2imzMLwas developed as an open-source converter that transforms Raman imaging data into imzML, a standardized common data format created and adopted by the mass spectrometry community. We successfully converted Raman datasets to imzML and visualized Raman images using open-source software designed for MSI applications.

Conclusion

Raman2imzMLenables both MSI and Raman images to be visualized using the same file format and the same software for a straightforward exploratory imaging analysis.
Optimal designs for phase II/III drug development programs including methods for discounting of phase II results
Authors: Erdmann Stella , Kirchner Marietta , Götte Heiko , Kieser Meinhard
Published: October 2020

Background

Go/no-go decisions after phase II and sample size chosen for phase III are usually based on phase II results (e.g., the treatment effect estimate of phase II). Due to the decision rule (only promising phase II results lead to phase III), treatment effect estimates from phase II that initiate a phase III trial commonly overestimate the true treatment effect. Underpowered phase III trials are the consequence. Optimistic findings may then not be reproduced, leading to the failure of potentially expensive drug development programs. For some disease areas these failure rates are described to be quite high: 62.5%.

Methods

We integrate the ideas of multiplicative and additive adjustment of treatment effect estimates after go decisions in a utility-based framework for optimizing drug development programs. The design of a phase II/III program, i.e., the “right amount of adjustment”, the allocation of the resources to phase II and III in terms of sample size, and the rule applied to decide whether to stop or to proceed with phase III influences its success considerably. Given specific drug development program characteristics (e.g., fixed and variable per patient costs for phase II and III, probable gain in case of market launch), optimal designs with respect to the maximal expected utility can be identified by the proposed Bayesian-frequentist approach. The method will be illustrated by application to practical examples characteristic for oncological studies.

Results

In general, our results show that the program set-ups with adjusted treatment effect estimate used for phase III planning are superior to the “naïve” program set-ups with respect to the maximal expected utility. Therefore, we recommend considering an adjusted phase II treatment effect estimate for the phase III sample size calculation. However, there is no one-fits-all design.

Conclusion

Individual drug development planning for a specific program is necessary to find the optimal design. The optimal choice of the design parameters for a specific drug development program at hand can be found by our user friendly R Shiny application and package (both assessable open-source via [1]).
Training improves the handling of inhaler devices and reduces the severity of symptoms in geriatric patients suffering from chronic-obstructive pulmonary disease
Authors: Luley Marie-Christine , Loleit Tobias , Knopf Elmar , Djukic Marija , Criée Carl-Peter , Nau Roland
Published: October 2020

Purpose

Elderly patients with impaired vision, cognitive decline or motor/sensory disturbances of their fingers suffering from chronic-obstructive pulmonary disease (COPD) encounter difficulties in handling inhaler devices used as the cornerstones of treatment of pulmonary obstruction. Many elderly patients make severe mistakes which impede adequate drug delivery to the bronchioles. This multimodal training program was designed to reduce the number of handling mistakes of inhaler devices.

Methods

From October 1, 2016 to September 30, 2017, a prospective intervention study was conducted in 38 in-patients > 65 years (median age 79 years) with previously diagnosed COPD. The effect of an 8-day intervention comprising daily counselling and video demonstration according to the recommendations of the German Airway League on the frequency of mistakes during handling of inhaler devices, the forced expiratory volume in 1 s (FEV1), the forced vital capacity (FVC) and the perception of symptoms (COPD Assessment Test, CAT) were studied. Measurements on days 1 and 8 were compared by Wilcoxon signed rank test.

Results

The number of handling mistakes per patient decreased as a consequence of the intervention from 3.0 (0–7) to 0.5 (0–6) [median (minimum-maximum; p < 0.0001)]. The CAT Score decreased from 19.5 (14/24) to 14.5 (10.75/21) [median (25./75. percentile; p < 0.0001) indicating a substantial reduction of clinical symptoms. Conversely, FEV1 and FVC only slightly increased (difference statistically not significant). At study entry, the number of handling mistakes was inversely correlated with the Mini Mental Status Test (MMST) score (p = 0.01). The reduction of the number of handling mistakes during the intervention was not correlated with the MMST.

Conclusion

In COPD, intensive training for 8 days improved the handling of inhalers and reduced clinical symptoms in geriatric patients. Patients with cognitive abnormalities also benefitted from this intervention.

Trial registration

German Clinical Trials Registry DRKS00023196, date of registration September 29, 2020 (retrospectively registered).
Frequency of thrombophilia associated genes variants: population-based study
Authors: Wawrusiewicz-Kurylonek Natalia , Krętowski Adam Jacek , Posmyk Renata
Published: October 2020

Background

Thrombophilia is a hypercoagulable state that may have a genetic basis (inherited) or can be acquired. It is a multifactorial condition and only the mutual interactions between the environment and genes may lead to the development of clinical manifestation. This state is the main factor promoting venous (rarely arterial) thromboembolism (VTE). Inherited thrombophilia is mainly associated with two pathogenic variants in the V coagulation factor (FV) and the prothrombin (FII) genes. The aim of our study was to evaluate the frequency of two pathogenic variants in FII and FV genes as inherited thrombophilia factors in a group within the Polish population in comparison with other described populations.

Methods

All studied groups consisted of 633 unrelated patients aged between 18 and 70. Individuals in the research group come from the Podlasie region of Poland. Genotyping of FII and FV variants was performed using the 7900HT Fast Real-Time PCR System and were genotyped by TaqMan assay.

Results

The pathogenic allele frequency for A allele was 0.03 (3%) and 0.07 (7%) for FII and FV genes, respectively. The GA/AA genotypes (c.*97G > A variant) were observed in only 33 (5.03%) individuals in the studied group. Additionally, the frequency of GA/AA genotypes was over 17.4% in the coagulation factor V. Co-incidence of heterozygous genotype GA of variants FII and FV genes was observed in only 4 subjects.

Conclusion

The FII gene variant shown in our study is less frequent than in other European countries (about 6%). In contrast, the A allele of the FV gene occurs with a frequency similar to that of Northern, Central and South Central Europe (about 5%).
The IL-6 rs12700386 polymorphism is associated with an increased risk of developing osteoarthritis in the knee in the Chinese Han population: a case-control study
Authors: Yang Hui , Zhou Xindie , Xu Dongmei , Chen Gang
Published: October 2020

Background

This case-control study aims to examine the association between the Interleukin-6 (IL-6) rs12700386 polymorphism and the increased risk of developing osteoarthritis (OA) in the knee in the Chinese Han population.

Methods

We extracted DNA from 763 subjects (352 OA patients and 411 healthy controls). The relative expression levels of IL-6 in blood samples of patients with knee OA was determined by quantitative reverse transcription PCR (qRT-PCR) and polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) was used for genotyping the IL-6 gene polymorphism.

Results

We found that the IL-6 polymorphism rs12700386 enhanced patient susceptibility to developing knee OA. Based on a subgroup analysis, the risk of developing knee OA was elevated in smokers, drinkers, and subjects ≥55 years old or with BMI ≥ 25 kg/m2. The combination of smoking, drinking, and having the rs12700386 genotype led to an increase in the risk of developing knee OA, indicating that an underlying interaction between gene and environment exists. The rs12700386 genotype was found to be correlated with an increase in IL-6 expression. We also found that IL-6 levels were significantly higher in the CC genotype compared to the GG genotype carriers in OA patients.

Conclusion

These data suggest that the rs12700386 polymorphism in the IL-6 gene leads to an increase in the risk of knee OA in Chinese Han individuals.
The personal and clinical impact of screen-detected maternal rheumatic heart disease in Uganda: a prospective follow up study
Authors: Voleti Sonia , Okello Emmy , Murali Meghna , Sarnacki Rachel , Majwala Albert , Ssembatya Renny , Bakka Olivia , Namisanvu Henriator , Njeri Angela , Matovu Alphonsus , DeStigter Kristen , Sable Craig , Beaton Andrea
Published: October 2020

Background

Pre-existing maternal cardiac disease is a significant contributor to adverse maternal, fetal, and neonatal outcomes. In 2015–2017, our team conducted the first community-based study of maternal rheumatic heart disease (RHD) in sub-Saharan Africa and identified RHD in 88% of those with pre-existing heart disease.

Here we conducted a follow up investigation of women previously identified with RHD, describing clinical and echocardiographic outcomes, identifying barriers to medical adherence and evaluating the personal impact of RHD.

Methods

A 2 week prospective follow up was completed at sites in Central and Eastern Uganda. Participants underwent a three-step mixed methods study comprising of 1) direct structured interview targeting clinical history and medication adherence, 2) echocardiogram to evaluate left-sided heart valves, and 3) semi-structured guideline interview to elicit personal impacts of RHD.

Results

The team evaluated 40 (80%) of the original 51 mothers with RHD at a median post-partum time of 2.5 years after delivery (IQR 0.5). Echocardiographic data showed improvement in nine women with the remaining 31 women showing stable echocardiographic findings. Adherence to Benzathine penicillin G (BPG) prophylaxis was poor, with 70% of patients either poorly adherent or non-adherent.

Three major themes emerged from interviews: 1) social determinants of health (World Health Organization, Social determinants of health, 2019) negatively affecting healthcare, 2) RHD diagnosis negatively affecting female societal wellbeing, 3) central role of spouse in medical decision making.

Conclusions

Screening echocardiography can identify women with pre-existing rheumatic heart disease during pregnancy, but long-term follow-up in Uganda reveals adherence to medical care following diagnosis, including BPG, is poor. Additionally, mothers diagnosed with RHD may experience unintended consequences such as social stigmatization. As identification of occult RHD is critical to prevent adverse pregnancy outcomes, further research is needed to determine how to best support women who face a new diagnosis of RHD, and to determine the role of screening echocardiography in high-risk settings.
Is hypofractionated whole pelvis radiotherapy (WPRT) as well tolerated as conventionally fractionated WPRT in prostate cancer patients? The HOPE trial
Authors: Mendez Lucas C. , Arifin Andrew J. , Bauman Glenn S. , Velker Vikram M. , Ahmad Belal , Lock Michael , Venkatesan Varagur M. , Sexton Tracy L. , Rodrigues George B. , Chen Jeff , Schaly Bryan , Warner Andrew , D’Souza David P.
Published: October 2020

Background

Patients with high-risk prostate cancer are at increased risk of lymph node metastasis and are thought to benefit from whole pelvis radiotherapy (WPRT). There has been recent interest in the use of hypofractionated radiotherapy in treating prostate cancer. However, toxicity and cancer outcomes associated with hypofractionated WPRT are unclear at this time. This phase II study aims to investigate the impact in quality of life associated with hypofractionated WPRT compared to conventionally fractionated WPRT.

Methods

Fifty-eight patients with unfavourable intermediate-, high- or very high-risk prostate cancer will be randomized in a 1:1 ratio between high-dose-rate brachytherapy (HDR-BT) + conventionally fractionated (45 Gy in 25 fractions) WPRT vs. HDR-BT + hypofractionated (25 Gy in 5 fractions) WPRT. Randomization will be performed with a permuted block design without stratification. The primary endpoint is late bowel toxicity and the secondary endpoints include acute and late urinary and sexual toxicity, acute bowel toxicity, biochemical failure-, androgen deprivation therapy-, metastasis- and prostate cancer-free survival of the hypofractionated arm compared to the conventionally fractionated arm.

Discussion

To our knowledge, this is the first study to compare hypofractionated WPRT to conventionally fractionated WPRT with HDR-BT boost. Hypofractionated WPRT is a more attractive and convenient treatment approach, and may become the new standard of care if demonstrated to be well-tolerated and effective.

Trial registration

This trial was prospectively registered in ClinicalTrials.gov as NCT04197141 on December 12, 2019.
Integrated analysis of serum lipid profile for predicting clinical outcomes of patients with malignant biliary tumor
Authors: Sun Lejia , Ji Xin , Wang Dongyue , Guan Ai , Xiao Yao , Xu Haifeng , Du Shunda , Xu Yiyao , Zhao Haitao , Lu Xin , Sang Xinting , Zhong Shouxian , Yang Huayu , Mao Yilei
Published: October 2020

Background

Serum lipids were reported to be the prognostic factors of various cancers, but their prognostic value in malignant biliary tumor (MBT) patients remains unclear. Thus we aim to assess and compare prognosis values of different serum lipids, and construct a novel prognostic nomogram based on serum lipids.

Methods

Patients with a confirmed diagnosis of MBT at our institute from 2003 to 2017 were retrospectively reviewed. Prognosis-related factors were identified via univariate and multivariate Cox regression analyses. Then the novel prognostic nomogram and a 3-tier staging system were constructed based on these factors and further compared to the TNM staging system.

Results

A total of 368 patients were included in this study. Seven optimal survival-related factors—TC/HDL >  10.08, apolipoprotein B >  0.9 g/L, lipoprotein> 72 mg/L, lymph node metastasis, radical cure, CA199 > 37 U/mL, and tumor differentiation —were included to construct the prognostic nomogram. The C-indexes in training and validation sets were 0.738 and 0.721, respectively. Besides, ROC curves, calibration plots, and decision curve analysis all suggested favorable discrimination and predictive ability. The nomogram also performed better predictive ability than the TNM system and nomogram without lipid parameters. And the staging system based on nomogram also presented better discriminative ability than TNM system (P < 0.001).

Conclusions

The promising prognostic nomogram based on lipid parameters provided an intuitive method for performing survival prediction and facilitating individualized treatment and was a great complement to the TNM staging system in predicting overall survival.
Epidemiology of the extent of recreational noise exposure and hearing protection use: cross-sectional survey in a nationally representative UK adult population sample
Authors: Armitage Christopher J. , Loughran Michael T. , Munro Kevin J.
Published: October 2020

Background

Hearing loss is prevalent and disabling, yet little is known about the extent of recreational noise exposure and hearing protection use. The aim of the present research was to estimate the extent of recreational noise exposure and hearing protection use in a sample representative of the UK adult population.

Methods

We conducted a cross-sectional survey of 10,401 UK adults who were representative of the population.

Results

More than 7000 people (n = 7590, 73.0%) reported exposure to recreational noise excluding headphone and earphone use in the last 12 months. Just 158 people (2.1%) reported wearing hearing protection for every noisy recreational activity. Age (younger people) and beliefs of a behavioral (as opposed to genetic) cause of hearing loss were predictive of both higher recreational noise exposure and greater hearing protection use. Men were more exposed to recreational noise but women were less likely to use hearing protection.

Conclusions

For the first time, the present research quantifies the recreational noise exposure and low levels of hearing protection use in a representative sample of the UK population. The biggest public health gains are likely to be achieved through interventions targeted at younger people and in explaining behavioral (as opposed to genetic) causes of hearing loss.
Predictors of undesirable treatment outcomes of severe acute malnutrition among inpatient children in Addis Ababa, Ethiopia: a retrospective cohort study
Authors: Negussie Absalat Serawit , Tadesse Amare Worku
Published: October 2020

Background

In 2018, malnutrition contributed to 45% of all global cause of child death. These early child deaths were due to conditions that could either be prevented or treated with basic interventions. Hence, this study intended to provide a quantitative estimate of factors associated with undesirable treatment outcomes of severe acute malnutrition (SAM).

Methods

We studied a retrospective cohort of 304 children aged 6–59 months with complicated SAM admitted to Yekatit 12 Hospital Medical College from 2013 to 2016. We extracted data from hospital records on nutritional status, socio-demographic factors and medical conditions during admission. The analysis was carried out using SPSS version 20. The Kaplan-Meier estimator was employed to analyze the recovery rate of the children treated for SAM and multivariable Cox regression was used to determine factors that predict inpatient undesirable treatment outcomes.

Result

From a total of 304 children 6–59 months with SAM, 133 (51.4%) were boys. Marasmus was the most common type (132 (51%)) of severe acute malnutrition. The recovery, death and defaulter rate were 70.4, 12.2 and 8.2% respectively. The main predictors of undesirable treatment outcomes were found to be the presence of HIV antibody (AHR = 3.208; 95% CI: [1.045–9.846]) and sepsis (AHR = 7.677, 95% CI: [2.320–25.404]).

Conclusion

The study revealed that the overall treatment outcomes were below the SPHERE standard recommendation. The main predictors of undesirable treatment outcomes among inpatient children treated for SAM were HIV and sepsis. Intervention to reduce undesirable treatment outcomes should focus on comorbidities, especially HIV and sepsis.
How to interact with medical terminologies? Formative usability evaluations comparing three approaches for supporting the use of MedDRA by pharmacovigilance specialists
Authors: Marcilly Romaric , Douze Laura , Ferré Sébastien , Audeh Bissan , Bobed Carlos , Lillo-Le Louët Agnès , Lamy Jean-Baptiste , Bousquet Cédric
Published: October 2020

Background

Medical terminologies are commonly used in medicine. For instance, to answer a pharmacovigilance question, pharmacovigilance specialists (PVS) search in a pharmacovigilance database for reports in relation to a given drug. To do that, they first need to identify all MedDRA terms that might have been used to code an adverse reaction in the database, but terms may be numerous and difficult to select as they may belong to different parts of the hierarchy. In previous studies, three tools have been developed to help PVS identify and group all relevant MedDRA terms using three different approaches: forms, structured query-builder, and icons. Yet, a poor usability of the tools may increase PVS’ workload and reduce their performance. This study aims to evaluate, compare and improve the three tools during two rounds of formative usability evaluation.

Methods

First, a cognitive walkthrough was performed. Based on the design recommendations obtained from this evaluation, designers made modifications to their tools to improve usability. Once this re-engineering phase completed, six PVS took part in a usability test: difficulties, errors and verbalizations during their interaction with the three tools were collected. Their satisfaction was measured through the System Usability Scale. The design recommendations issued from the tests were used to adapt the tools.

Results

All tools had usability problems related to the lack of guidance in the graphical user interface (e.g., unintuitive labels). In two tools, the use of the SNOMED CT to find MedDRA terms hampered their use because French PVS were not used to it. For the most obvious and common terms, the icons-based interface would appear to be more useful. For the less frequently used MedDRA terms or those distributed in different parts of the hierarchy, the structured query-builder would be preferable thanks to its great power and flexibility. The form-based tool seems to be a compromise.

Conclusion

These evaluations made it possible to identify the strengths of each tool but also their weaknesses to address them before further evaluation. Next step is to assess the acceptability of tools and the expressiveness of their results to help identify and group MedDRA terms.
Functional analysis and evaluation of respiratory cilia in healthy Chinese children
Authors: Lee So-Lun , O’Callaghan Christopher , Lau Yu-Lung , Lee Chun-Wai Davy
Published: October 2020

Background

To aid in the diagnosis of Primary Ciliary Dyskinesia (PCD) and to evaluate the respiratory epithelium in respiratory disease, normal age-related reference ranges are needed for ciliary beat frequency (CBF), beat pattern and ultrastructure. Our aim was to establish reference ranges for healthy Chinese children.

Methods

Ciliated epithelial samples were obtained from 135 healthy Chinese children aged below 18 years by brushing the inferior nasal turbinate. CBF and beat pattern were analysed from high speed video recordings. Epithelial integrity and ciliary ultrastructure were assessed using transmission electronic microscopy.

Results

The mean CBF from 135 children studied was 10.1 Hz (95% CI 9.8 to 10.4). Approximately 20% (ranged 18.0–24.2%) of ciliated epithelial edges were found to have areas of dyskinetically beating cilia. Normal beat pattern was observed in ciliated epithelium from all subjects. We did not find any effect of exposure to second hand smoke on CBF in our subjects. Microtubular defects were found in 9.3% of all of the cilia counted in these children, while other ciliary ultrastructural defects were found in less than 3%.

Conclusions

We established the reference range for CBF, beat pattern and ultrastructure in healthy Chinese children. Using similar methodology, we found a lower overall mean CBF than previously obtained European values. This study highlights the need to establish normative data for ciliary function in different populations.
T-cell lymphoma with a granulomatous lesion of the lungs after autologous hematopoietic stem cell transplantation for Epstein–Barr virus-positive diffuse large B-cell lymphoma: a unique rare case of metachronous B-cell and T-cell lymphoma
Authors: Kajimoto Yusuke , Terasaki Yasuhiro , Terasaki Mika , Kunugi Shinobu , Okabe Yugo , Wakita Satoshi , Inokuchi Koiti , Shimizu Akira
Published: October 2020

Background

Epstein–Barr virus (EBV) is associated with the pathogenesis of a variety of malignancies, most notably lymphomas. Especially in the background of immunodeficiency, such as primary immunodeficiency disorder (PID) and post-transplant lymphoproliferative disorder (PTLD), the role of EBV might be crucial. PIDs are rare heterogeneous diseases affecting the development and/or the function of the innate and adaptive immune system. Malignancy is the second-highest cause of death after infection, and lymphoma accounts for about half of malignancies. The most frequently reported lymphoma type is diffuse large B-cell lymphoma (DLBCL) and the incidence of T-cell lymphoma is rare. PTLDs are also rare serious lymphoid and/or plasmacytic proliferative disorders that occur after undergoing solid organ or hematopoietic stem cell transplantation (HSCT). In the context of HSCT, most reported PTLDs have occurred in patients who received allogenic HSCT, but only a few cases have been reported in autologous HSCT (AutoHSCT) recipients.

Case presentation

A 53-year-old female patient initially presented with enlargement of the left cervical lymph nodes and was diagnosed with EBV-positive DLBCL. She was treated with R-CHOP, R-ACES, and AutoHSCT and went into remission. Four years later, computed tomography results revealed multiple lung nodules and abnormal infiltration, and sustained and progressing hypogammaglobulinemia was observed. The pathological specimen of video-assisted thoracoscopic surgical lung biopsy demonstrated extensive invasion of lymphocytes with notable granuloma findings. Flow cytometric immunophenotyping analysis showed that lymphocytes were positive for CD3 and CD5; especially, CD3 was expressed in the cytoplasm. Southern blot analysis revealed rearrangements of the T-cell receptor Cβ1 gene. She was diagnosed with peripheral T-cell lymphoma, not otherwise specified, accompanied by notable granulomatous lesions.

Conclusion

Here, as a unique case of metachronous B-cell and T-cell lymphoma, we report a rare case of T-cell lymphoma that mainly affected the lungs with the presentation of notable granulomatous findings following AutoHSCT for EBV-positive DLBCL at the age of 53 years. These lung lesions of granulomatous T-cell lymphoma could be related to the underlying primary immunodeficiency background associated with sustained hypogammaglobulinemia.
Wild edible plants collected and consumed by the locals in Daqinggou, Inner Mongolia, China
Authors: Sachula  , Geilebagan  , Zhang Yan-ying , Zhao Hui , Khasbagan
Published: October 2020

Background

Knowledge of wild edible plants is an important part of traditional knowledge. It is closely related to traditional human agriculture, as well as biodiversity. This study aimed to conduct a detailed investigation and evaluation of wild edible plants that are collected and consumed by the Mongolian and Han locals in Daqinggou and to provide valuable data for the development and utilization of plant resources.

Methods

In the 9 site visits to the area of Daqinggou during the period of 2017–2019, the authors used key informant interviews, semistructured interviews, and questionnaires to collect utilization information regarding precollected species of local wild edible plants. By combining the data obtained from 101 key informants, the authors used the Cultural Food Significance Index (CFSI), a quantitative index to evaluate the relative importance of the wild edible plants that were discussed in the aforementioned interviews.

Results

The investigation results show that the Mongolian people provided 67 folk names, corresponding to 57 wild plants, and the Han Chinese provided 58 folk names, corresponding to 49 wild plants. A total of 61 edible wild plant species belonging to 29 families and 52 genera were recorded as edible resources for the locals in Daqinggou. The uses include grains, oil and fat resources, vegetables, fruits, beverages, condiments, and snacks. The most commonly reported purpose of wild edible plants is using them as vegetables, followed by using them as beverages and fruits. The most widely used edible parts are fruits, leaves, and other aerial parts. Eating raw and cooked plants are the usual methods of consuming wild edible plants according to the locals. In addition, the CFSI of 61 wild edible plant species shows that 27 species have characteristics of medical food.

Conclusions

The knowledge and experience of naming and consuming wild plants by the Mongolian people and Han Chinese in Daqinggou are an important manifestation of the direct interaction between locals and plants. The CSFI evaluation of the wild edible plants consumed by the locals in Daqinggou establishes the utilization of some wild plants as part of the traditional knowledge of medical food.
The effects of exergaming on pain, postural control, technology acceptance and flow experience in older people with chronic musculoskeletal pain: a randomised controlled trial
Authors: Ditchburn Jae-Llane , van Schaik Paul , Dixon John , MacSween Alasdair , Martin Denis
Published: October 2020

Background

Older people with chronic musculoskeletal pain are at risk of falls. This study aimed to investigate the effects of exergaming on pain and postural control in older people with chronic musculoskeletal pain. Secondary outcomes were technology acceptance, flow experience, perceived physical exertion, expended mental effort and heart rate.

Methods

Fifty four older adults (age: 71 ± 5 years) with chronic musculoskeletal pain were randomised into 2 groups. Group 1 received exergaming training using the Interactive Rehabilitation and Exercise System (IREX®). Group 2 undertook traditional gym-based exercise (TGB). Both groups completed twice weekly 40-min exercise sessions for 6 weeks. Perceived pain was measured using a numeric pain rating scale and the Multidimensional Affect and Pain Survey questionnaire. Postural control was measured as sway using a Kistler™ force platform. Technology acceptance was measured with the Unified Theory of Acceptance and Use of Technology questionnaire and flow experience with the Flow State Scale. Physiological measures of perceived physical exertion, expended mental effort and heart rate were recorded during all sessions.

Results

The exergaming group demonstrated significant reductions in pain intensity and thermal pain including a near significant approach in physical engagement in comparison to TGB group. Although no intervention effects on postural control were found, the exergaming group showed significant improvements in three sway measures (AP SD, ML SD and AP range) over time whereas significant improvements in ML range were found in the TGB group. Relating to technology acceptance, significant intervention effects on social influence and behavioural intention were found in the TGB group instead, although both groups demonstrated increases of acceptance over time. Regarding flow experience, concentration at task was significantly influenced in the TGB group and significant increases in flow variables over time were observed in both groups. Significant increases over time in perceived physical exertion and expended mental effort were found in both groups.

Conclusion

Our findings support the potential of exergaming to alleviate pain and improve balance in older people with chronic musculoskeletal pain. Both forms of exercise are acceptable, intrinsically motivating and show evidence of benefit to older people with chronic musculoskeletal pain.

Trial registration

ClinicalTrials.gov Identifier:NCT04029285(retrospectively registered, July 23, 2019)
Evaluation of a genetic risk score for severity of COVID-19 using human chromosomal-scale length variation
Authors: Toh Christopher , Brody James P.
Published: October 2020

Introduction

The course of COVID-19 varies from asymptomatic to severe in patients. The basis for this range in symptoms is unknown. One possibility is that genetic variation is partly responsible for the highly variable response. We evaluated how well a genetic risk score based on chromosomal-scale length variation and machine learning classification algorithms could predict severity of response to SARS-CoV-2 infection.

Methods

We compared 981 patients from the UK Biobank dataset who had a severe reaction to SARS-CoV-2 infection before 27 April 2020 to a similar number of age-matched patients drawn for the general UK Biobank population. For each patient, we built a profile of 88 numbers characterizing the chromosomal-scale length variability of their germ line DNA. Each number represented one quarter of the 22 autosomes. We used the machine learning algorithm XGBoost to build a classifier that could predict whether a person would have a severe reaction to COVID-19 based only on their 88-number classification.

Results

We found that the XGBoost classifier could differentiate between the two classes at a significant level (p = 2 · 10−11) as measured against a randomized control and (p = 3 · 10−14) as measured against the expected value of a random guessing algorithm (AUC = 0.5). However, we found that the AUC of the classifier was only 0.51, too low for a clinically useful test.

Conclusion

Genetics play a role in the severity of COVID-19, but we cannot yet develop a useful genetic test to predict severity.
An ontology based modeling framework for design of educational technologies
Authors: Chimalakonda Sridhar , Nori Kesav V.
Published: October 2020

Despite rapid progress, most of the educational technologies today lack a strong instructional design knowledge basis leading to questionable quality of instruction. In addition, a major challenge is to customize these educational technologies for a wide range of customizable instructional designs. Ontologies are one of the pertinent mechanisms to represent instructional design in the literature. However, existing approaches do not support modeling of flexible instructional designs. To address this problem, in this paper, we propose an ontology based framework for systematic modeling of different aspects of instructional design knowledge based on domain patterns. As part of the framework, we present ontologies for modeling goals, instructional processes and instructional material. We demonstrate the ontology framework by presenting instances of the ontology for the large scale case study of adult literacy in India (287 million learners spread across 22 Indian Languages), which requires creation of hundreds of similar but varied eLearning Systems based on flexible instructional designs. The implemented framework is available at http://rice.iiit.ac.in and is transferred to National Literacy Mission Authority of Government of India. The proposed framework could be potentially used for modeling instructional design knowledge for school education, vocational skills and beyond.
High-performance printed electronics based on inorganic semiconducting nano to chip scale structures
Authors: Dahiya Abhishek Singh , Shakthivel Dhayalan , Kumaresan Yogeenth , Zumeit Ayoub , Christou Adamos , Dahiya Ravinder
Published: October 2020

The Printed Electronics (PE) is expected to revolutionise the way electronics will be manufactured in the future. Building on the achievements of the traditional printing industry, and the recent advances in flexible electronics and digital technologies, PE may even substitute the conventional silicon-based electronics if the performance of printed devices and circuits can be at par with silicon-based devices. In this regard, the inorganic semiconducting materials-based approaches have opened new avenues as printed nano (e.g. nanowires (NWs), nanoribbons (NRs) etc.), micro (e.g. microwires (MWs)) and chip (e.g. ultra-thin chips (UTCs)) scale structures from these materials have been shown to have performances at par with silicon-based electronics. This paper reviews the developments related to inorganic semiconducting materials based high-performance large area PE, particularly using the two routes i.e. Contact Printing (CP) and Transfer Printing (TP). The detailed survey of these technologies for large area PE onto various unconventional substrates (e.g. plastic, paper etc.) is presented along with some examples of electronic devices and circuit developed with printed NWs, NRs and UTCs. Finally, we discuss the opportunities offered by PE, and the technical challenges and viable solutions for the integration of inorganic functional materials into large areas, 3D layouts for high throughput, and industrial-scale manufacturing using printing technologies.
Application of deep learning in detecting neurological disorders from magnetic resonance images: a survey on the detection of Alzheimer’s disease, Parkinson’s disease and schizophrenia
Authors: Noor Manan Binth Taj , Zenia Nusrat Zerin , Kaiser M Shamim , Mamun Shamim Al , Mahmud Mufti
Published: October 2020

Neuroimaging, in particular magnetic resonance imaging (MRI), has been playing an important role in understanding brain functionalities and its disorders during the last couple of decades. These cutting-edge MRI scans, supported by high-performance computational tools and novel ML techniques, have opened up possibilities to unprecedentedly identify neurological disorders. However, similarities in disease phenotypes make it very difficult to detect such disorders accurately from the acquired neuroimaging data. This article critically examines and compares performances of the existing deep learning (DL)-based methods to detect neurological disorders—focusing on Alzheimer’s disease, Parkinson’s disease and schizophrenia—from MRI data acquired using different modalities including functional and structural MRI. The comparative performance analysis of various DL architectures across different disorders and imaging modalities suggests that the Convolutional Neural Network outperforms other methods in detecting neurological disorders. Towards the end, a number of current research challenges are indicated and some possible future research directions are provided.
The impact of impression coping geometrical design on accuracy of implant impressions: an experimental study
Authors: Osman Motaz , Abubakr Neamat Hassan , Suliman Ahmed , Ziada Hassan
Published: October 2020

Aim

This in vitro study aimed to evaluate the effect of implant impression coping geometrical designs on the accuracy of open and closed impression techniques and in the parallel and nonparallel implant positions.

Material and methods

Three custom-made acrylic resin models of three tested implant systems (Straumann®, SIC Invent®, and Osstem®) with diverse coping geometrical designs were evaluated in simulated cases of two parallel and two nonparallel implants. The horizontal and vertical discrepancies were measured and analyzed.

Results

No statistically significant differences between the two impression techniques in either parallel or nonparallel implants were observed. The high retentive design of the Osstem system showed a statistically significant difference.

Conclusion

The geometrical design of the impression copings did not affect the accuracy for either the open and closed tray techniques. However, the high retentive coping design of the Osstem implant affected the accuracy in the open tray technique.
First month of the epidemic caused by COVID-19 in Italy: current status and real-time outbreak development forecast
Authors: Megna Rosario
Published: October 2020

Background

The first outbreak of COVID-19 in Italy occurred during the second half of February 2020 in some areas in the North of the country. Due to the high contagiousness of the infection, further spread by asymptomatic people, Italy has become in a few weeks the country with the greatest number of infected people in the world. The large number of severe cases among infected people in Italy led to the hospitalization of thousands of patients, with a heavy burden on the National Health Service.

Methods

We analyzed data provided daily by Italian Authorities for the period from 24 February 2020 to 30 March 2020. Considering such information, we developed a forecast model in real-time, based on the cumulative log-logistic distribution.

Results

A total of 101,739 infected individuals were confirmed until 30 March 2020, of which 14,620 recovered or discharged, and 11,591 deaths. Until the same date patients quarantined at home were 43,752, whereas hospitalized patients were 31,776, of which 3981 in intensive care. The active cases (i.e. the number of patients not yet recovered until that date) were 75,528. The forecast model estimated a number of infected persons for Italy of 234,000 about, and a duration of the epidemic of approximately 4 months.

Conclusions

One month after the first outbreaks there seemed to be the first signs of a decrease in the number of infections, showing that we could be now facing the descending phase of the epidemic. The forecast obtained thanks to our model could be used by decision-makers to implement coordinative and collaborative efforts in order to control the epidemic. The pandemic due to novel Coronavirus must be a warning for all countries worldwide, regarding a rapid and complete dissemination of information, surveillance, health organization, and cooperation among the states.