bluuebunny/crossref_metadata_2025 huggingface dataset:
Relapsing and progressive MS: the sex-specific perspective
Authors: Rommer Paulus Stefan , Ellenberger David , Hellwig Kerstin , Haas Judith , Pöhlau Dieter , Stahmann Alexander , Zettl Uwe Klaus ,   on behalf of the Scientific Advisory Group of the German MS-Register by the German MS Society
Published: September 2020

Background:

Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease whose aetiology is not fully understood. The female sex is clearly predominant, with a sex ratio between 2 and 3. In primary progressive MS the sex ratio almost balances out. Since the age at onset is higher for patients with progressive onset (POMS) than for relapsing onset (ROMS), it can be hypothesized that the age at onset is a decisive factor for the sex ratio.

Methods:

To address this aspect, we compare clinical and demographic data between females and males for the different disease courses within the population of the German MS Register by the German MS Society. Only patients with complete details in mandatory data items and a follow-up visit since 01. Jan 2018 were included.

Results:

A total of 18,728 patients were included in our analyses, revealing a female-to-male ratio of 2.6 (2.7 for patients with ROMS and 1.3 for POMS). The age at diagnosis is higher in patients with POMS (43.3 and 42.3 years for females and males versus 32.1 and 33.2 years, respectively). Females irrespective of disease course are statistically significantly more often affected by cognitive impairment (POMS: p = 0.013, ROMS: p = 0.001) and depression (POMS: p = 0.002, ROMS: 0.001) and suffer more often from pain (POMS and ROMS: p < 0.001). Fatigue is significantly more often seen in females with ROMS ( p < 0.001) but not in POMS. Females with ROMS retire significantly ( p < 0.001) earlier (42.8 versus 44.2 years) and to a greater extent than males (28 versus 24%). Disease progression was similar for women and men.

Conclusion:

Our analysis shows that clinical and demographic data differ more between disease courses than between men and women. For pain, depression and cognitive impairment the female sex is the decisive factor. Whether these factors are responsible for the earlier retirement of females with ROMS is not clear. Appropriate measures for optimization of symptomatic treatment as well as to promote employment should be taken.
How American virtue lost its identity: 1765–1980
Authors: Glanzer Perry L
Published: September 2020

Moral philosophy in early American collegiate education founded its understanding and pursuit of virtue on the theological truth that humans are made in God’s image. Therefore, to fulfill our purpose, we need to acquire creaturely analogues of God’s virtues. Later American moral philosophy scholars and texts, however, began to use a different rationale for teaching virtue—we need virtue to support American liberal democracy. As a result, by the late twentieth century, American moral educators at the collegiate level only focused on helping students develop a small set of virtues related to students’ professional and civic identities.
Effects of CX3CL1 inhibition on murine bleomycin-induced interstitial pneumonia
Authors: Yamada Soichi , Miyoshi Shion , Nishio Junko , Mizutani Satoshi , Yamada Zento , Kusunoki Natsuko , Sato Hiroshi , Kuboi Yoshikazu , Hoshino-Negishi Kana , Ishii Naoto , Imai Toshio , Mikami Tetsuo , Nakano Hiroyasu , Kawai Shinichi , Nanki Toshihiro
Published: September 2020

Background:

Treatment for interstitial pneumonia (IP) associated with collagen diseases has not been established. There is a need to elucidate the pathogenesis of IP and develop a novel therapy. We aimed to clarify the role of chemokine (C-X3-C motif) ligand 1 (CX3CL1, also known as fractalkine) in IP.

Methods:

Bleomycin (BLM) was intratracheally administered to C57BL/6 mice to induce IP. For treatment with control Ab or anti-CX3CL1 mAb, the mice were administered either Ab three times per week for 2 weeks from the day of BLM administration until euthanasia. Expressions of CX3CL1 and its unique receptor CX3CR1 in the lung tissue were examined by immunohistochemical analysis. Cellular infiltration and lung fibrosis were evaluated based on hematoxylin-eosin-staining and Sirius red staining of the lung tissue sections, respectively. Bronchoalveolar lavage fluid (BALF) cells were analyzed by flow cytometry.

Results:

CX3CL1 and CX3CR1 were strongly expressed in the lung tissue from mice with BLM-induced IP (BLM-IP). Treatment with anti-CX3CL1 mAb did not significantly alter inflammatory cell infiltration or fibrosis in the lung tissue. However, the number of M1-like macrophages in BALF was decreased and surface CD3 expression on T cells was increased by anti-CX3CL1 mAb treatment.

Conclusions:

Inhibition of CX3CL1 decreased inflammatory cells and may attenuate T cell activation in BALF. CX3CL1 inhibitor may have the potential to suppress the infiltration and activation of immune cells in IP.
Post-concussion states: How do we improve our patients’ outcomes? An Australian perspective
Authors: Thomas Elizabeth , Fitzgerald Melinda , Cowen Gill
Published: September 2020

There is limited data surrounding incidence and prevalence of concussion and the resulting post-concussion states. This creates difficulty when investigating ways to optimise patient management. It is proposed that a registry of patients presenting with symptoms and signs after a concussion, as part of a large scale TBI registry across Australia, would provide a starting point for future research with a view to improving the outcomes of patients experiencing symptoms and signs after concussion.
“Professional Development Is Really Key”: Experiences of School Counselors Engaging in Professional Development Focused on LGBTQ Youth
Authors: Beck Matthew J. , Wikoff Haley D.
Published: September 2020

This qualitative study explored the experiences and perspectives of eight school counselors who attended a lesbian, gay, bisexual, transgender, and queer (LGBTQ)–related professional development event at a Midwestern University. The researchers identified three themes: (a) commitment and motivation, (b) learning from and connecting with others, and (c) critical takeaways. This article outlines implications for practice and future research regarding how school counselors can become more intentionally engaged in LGBTQ-inclusive professional development activities.
School Counselors’ Work-Related Rumination as a Predictor of Burnout, Turnover Intentions, Job Satisfaction, and Work Engagement
Authors: Mullen Patrick R. , Backer Adrienne , Chae Nancy , Li Huijuan
Published: September 2020

We examined work-related rumination among 288 school counselors and its relationship to elements of their professional well-being. The composite of affective rumination, problem-solving pondering, and detachment individually predicted burnout, turnover intentions, job satisfaction, and work engagement. Our findings indicated that higher affective rumination coupled with lower problem-solving pondering predicted increased burnout and turnover intentions and decreased job satisfaction and work engagement. We describe the implications of these findings for school counselors and educators.
War Memory, Psychological Trauma, and Literary Witnessing: Afghan Cultural Production in Focus
Authors: Ullah Inayat
Published: September 2020

As non-literary accounts of post-traumatic stress disorder victims depict, and contribute to, history and memory, the present study uses the theoretical underpinnings of the psychological trauma theory to reflect on the flashbacks of Afghan trauma survivors, portrayed in the selected Afghan Anglophone fiction. The research project attempts to see how far the flashbacks of the traumatic memories of these characters contribute to the oft-quoted factual history. Borrowing from Caruth, Herman, Tal and LaCapra for the analysis, the study investigates the selected literary text to see how cultural productions from this war-torn country keep a record of the traumatic memories of the war that the Afghans were faced with during the Soviet invasion from 1979 to 1989. This trauma analysis of Atiq Rahimi’s Earth and Ashes (2002) shows that analyses of trauma-induced flashbacks in literary portrayals of traumatized characters may, simultaneously, contribute to the officially recorded history of the actual event of trauma. The study concludes that related literary texts may be studied in conjunction with factual historical documents to get a holistic picture of any traumatic event as well as the related memory.
Shoulder Injury Related to Vaccine Administration: Case Series of an Emerging Occupational Health Concern
Authors: Batra Sumeet , Page Bridget
Published: September 2020

Background:

Shoulder injury related to vaccine administration (SIRVA) is an increasingly recognized complication of improper vaccine administration. Due to the growing number of mandatory workplace vaccination programs, especially for annual influenza vaccine, it is essential that occupational health providers are aware of this condition to improve prevention and/or treatment of this condition when it arises. Therefore, we describe the clinical presentation and course of treatment of five cases of SIRVA that were seen in an employer-based Occupational Health Services Clinic (OHS) after mandatory influenza vaccine administration.

Methods:

A retrospective chart review was performed for five cases of SIRVA from 2017 to 2019.

Findings:

Five cases met clinical definition of SIRVA as defined by the National Vaccine Injury Compensation Program. All cases were of similar characteristics including gender, age range, and body mass index (BMI). All were treated using multiple modalities including medication, physical therapy, and modified work with eventual resolution of symptoms and full return to work.

Conclusions/Application to Practice:

Awareness of SIRVA is necessary in any occupational setting where vaccines are routinely administered. Avoidance of SIRVA by adhering to proper vaccination technique is crucial, as is awareness of how to recognize and manage the condition in affected employees to limit long-term impairment.
The Effect of Systemic Tranexamic Acid on Hypercoagulable Complications and Perioperative Outcomes Following Three-Column Osteotomy for Adult Spinal Deformity
Authors: Haddad Alexander F. , Ames Christopher P. , Safaee Michael , Deviren Vedat , Lau Darryl
Published: September 2020

Study Design:

Retrospective cohort study.

Objective:

Thoracolumbar 3-column osteotomy (3CO) is a powerful technique for correction of rigid adult spinal deformity (ASD). However, it can be associated with high-volume blood loss. This study seeks to investigate the efficacy and safety of tranexamic acid (TXA) in 3CO ASD patients.

Methods:

ASD patients who underwent 3CO from 2006 to 2019 were retrospectively reviewed. Outcomes were compared between TXA and non-TXA patients, and TXA doses.

Results:

A total of 365 ASD patients were included: 181 TXA and 184 non-TXA. The mean age was 64.6 years and 60.5% were female. Operative time was shorter in the TXA group (295.6 vs 320.2 minutes, P < .001). However, TXA was not associated with shorter operative time (β = −6.5 minutes, 95% CI −29.0 to 15.9, P = .567) after accounting for surgeon experience. There was no difference in blood loss (2020.2 vs 1914.1 mL, P = .437) between groups. Overall complications (37.0% vs 33.2%, P = .439), including hypercoagulable (2.2% vs 3.8%, P = .373) and cardiac (13.3% vs 7.1%, P = .050) complications were similar between groups. TXA was not independently associated with blood loss or TXA-related complications. Both groups had comparable intensive care unit (2.5 vs 2.0 days, P = .060) and hospital (8.9 vs 8.2 days, P = .190) stays. There were no differences in outcomes between TXA dosing subgroups.

Conclusions:

Systemic TXA use during 3CO for ASD surgery was not associated with decreased blood loss. TXA patients had shorter operative times, but this was driven mainly by surgeon experience on multivariate analysis. Routine use of TXA is safe and does not increase the incidence of hypercoagulable complications even at high doses.
Cumulative (and self-reinforcing) spatial inequalities: Interactions between accessibility and segregation in four Brazilian metropolises
Authors: Bittencourt Tainá A , Giannotti Mariana , Marques Eduardo
Published: September 2020

The inequalities that mark global society have been deepening worldwide. They materialize in cities, putting pressure on public transport systems for spatial and temporal supply, at the same time as mobility itself generates multifaceted inequalities. From empirical evidence of four socially and spatially distinct Brazilian cities — São Paulo, Rio de Janeiro, Curitiba, and Fortaleza — we explore how differences in scale, geography, class, and race are related to spatial segregation, leading to different levels of access to jobs by public transport in the global peripheral context. These juxtaposed and combined inequalities create highly unfair and strongly cumulative effects on some social groups, contributing to the reproduction of inequality. Based on public and open data and combining methodologies of spatial analysis to enhance comparability and reproducibility, we explore different areal units, time thresholds, and metrics in order to examine transport inequalities in different urban contexts and refine our results. Upper classes have higher accessibility than lower classes, whites have higher accessibility than blacks, and large cities are more unequal than smaller ones. However, racial inequalities combine and overlap with class and city inequalities, changing these dichotomic notions when multiple dimensions are considered. The groups that polarize social hierarchy also polarize the urban space, since the white upper class and the black lower class are more segregated, but the way segregation interacts with accessibility is not straightforward and varies according to the socio-spatial structure.
Visual Analog Pain Scores Reported to a Nurse and a Physician in a Postoperative Setting
Authors: McBride Trevor J. , Wilke Aaron , Chisholm Jamie , Martin Kevin D.
Published: September 2020

Background:

The purpose of this study was to compare postoperative foot and ankle patient-reported visual analog pain scores (VAS) to nursing staff and the treating surgeon during a single encounter. Prior literature established preoperative patients reported higher pain scores to a surgeon as compared to nursing staff. We hypothesized that there will be no differences in postoperative patients’ pain scores when reporting to nursing staff vs a surgeon.

Methods:

This study was a retrospective cohort of 201 consecutive postoperative foot and ankle patients with 3 follow-up encounters treated by a single surgeon. The patients were asked to rate their pain intensity using the VAS with 0 “no pain” and 10 “worst pain” at 2, 6, and 12 weeks postoperatively by a nurse and surgeon.

Results:

At all time intervals, the mean pain score was significantly higher when reported to the surgeon, although these were not clinically relevant. The mean scores at 2 weeks were 2.8 reported to the surgeon and 2.5 reported to the nurse ( P < .001). The mean scores at 6 weeks were 2.0 reported to the surgeon and 1.8 reported to the nurse ( P = .002). The mean scores at 12 weeks were 2.3 reported to the surgeon and 2.0 reported to the nurse ( P = .005).

Conclusion:

This study found that postoperative foot and ankle patients did not overemphasize their VAS pain scores to the physician vs nursing staff. These findings contrast with our 2 previous studies that found preoperative and nonoperative patients reported clinically significant higher scores to the surgeon.

Level of Evidence:

Level III, comparative study.
Sphingolipid Metabolism at the ER-Golgi Contact Zone and Its Impact on Membrane Trafficking
Authors: Goto Asako , Mizuike Aya , Hanada Kentaro
Published: September 2020

Proteins and lipids represent the two major constituents of biological membranes. Different organelles have different lipid compositions, which may be crucial for the execution and control of various organelle-specific functions. The interorganellar transport of lipids is dominated by mechanisms that are distinct from the vesicular mechanisms that underlie the interorganellar transport of proteins. Lipid transfer proteins (LTPs) efficiently and accurately mediate the trafficking of membrane lipids at the interfaces between different organelles. In this review, which focuses on sphingolipids, we describe the coordinated synthesis and transfer of lipids that occur at the endoplasmic reticulum (ER)-Golgi apparatus contact zones and discuss the impacts of lipid metabolism on membrane trafficking from the trans-Golgi network (TGN).
Assessing the impact of case-mix heterogeneity in individual participant data meta-analysis: Novel use of I2 statistic and prediction interval
Authors: Vo Tat-Thang , Porcher Raphaël , Vansteelandt Stijn
Published: September 2020

Case mix differences between trials form an important factor that contributes to the statistical heterogeneity observed in a meta-analysis. In this paper, we propose two methods to assess whether important heterogeneity would remain if the different trials in the meta-analysis were conducted in one common population defined by a given case-mix. To achieve this goal, we first standardize results of different trials over the case-mix of a target population. We then quantify the amount of heterogeneity arising from case-mix and beyond case-mix reasons by using corresponding I2 statistics and prediction intervals. These new approaches enable a better understanding of the overall heterogeneity between trial results, and can be used to support standard heterogeneity assessments in individual participant data meta-analysis practice.
Increased nocturnal arterial pulsation frequencies of obstructive sleep apnoea patients is associated with an increased number of lapses in a psychomotor vigilance task
Authors: Kainulainen Samu , Duce Brett , Korkalainen Henri , Leino Akseli , Huttunen Riku , Kalevo Laura , Arnardottir Erna S. , Kulkas Antti , Myllymaa Sami , Töyräs Juha , Leppänen Timo
Published: September 2020

Objectives

Besides hypoxaemia severity, heart rate variability has been linked to cognitive decline in obstructive sleep apnoea (OSA) patients. Thus, our aim was to examine whether the frequency domain features of a nocturnal photoplethysmogram (PPG) can be linked to poor performance in the psychomotor vigilance task (PVT).

Methods

PPG signals from 567 suspected OSA patients, extracted from Type 1 diagnostic polysomnography, and corresponding results of PVT were retrospectively examined. The frequency content of complete PPGs was determined, and analyses were conducted separately for men (n=327) and women (n=240). Patients were grouped into PVT performance quartiles based on the number of lapses (reaction times ≥500 ms) and within-test variation in reaction times. The best-performing (Q1) and worst-performing (Q4) quartiles were compared due the lack of clinical thresholds in PVT.

Results

We found that the increase in arterial pulsation frequency (APF) in both men and women was associated with a higher number of lapses. Higher APF was also associated with higher within-test variation in men, but not in women. Median APF (β=0.27, p=0.01), time spent under 90% saturation (β=0.05, p<0.01), female sex (β=1.29, p<0.01), older age (β=0.03, p<0.01) and subjective sleepiness (β=0.07, p<0.01) were significant predictors of belonging to Q4 based on lapses. Only female sex (β=0.75, p<0.01) and depression (β=0.91, p<0.02) were significant predictors of belonging to Q4 based on the within-test variation.

Conclusions

In conclusion, increased APF in PPG provides a possible polysomnography indicator for deteriorated vigilance especially in male OSA patients. This finding highlights the connection between cardiorespiratory regulation, vigilance and OSA. However, our results indicate substantial sex-dependent differences that warrant further prospective studies.
Constrictive bronchiolitis in diffuse idiopathic pulmonary neuroendocrine cell hyperplasia
Authors: Samhouri Bilal F. , Azadeh Natalya , Halfdanarson Thorvardur R. , Yi Eunhee S. , Ryu Jay H.
Published: September 2020

Background

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is characterised by multifocal proliferation of neuroendocrine cells and belongs in the spectrum of pulmonary neuroendocrine tumours. Some patients with DIPNECH develop airflow obstruction but the relationship between the two entities remains unclear.

Methods

We performed a computer-assisted search of the Mayo Clinic's electronic medical records for biopsy-proven cases of DIPNECH. We extracted clinical, pulmonary function, imaging and histopathological data along with treatments and outcomes.

Results

Among 44 patients with DIPNECH 91% were female and the median age was 65 years (interquartile range 56–69 years); 73% were never-smokers. Overall, 38 patients (86%) had respiratory symptoms including cough (68%) and dyspnoea (30%); 45% were previously diagnosed to have asthma or COPD. Pulmonary function testing showed an obstructive pattern in 52%, restrictive pattern in 11%, mixed pattern in 9%, nonspecific pattern in 23%, and was normal in 5%. On chest computed tomography scan, 95% manifested diffuse nodules and 77% manifested mosaic attenuation. For management, 25% of patients were observed without pharmacological therapy, 55% received an inhaled bronchodilator, 41% received an inhaled corticosteroid, 32% received octreotide; systemic steroids, azithromycin, or combination chemotherapy was employed in four patients (9%). Of 24 patients with available follow-up pulmonary function tests, 50% remained stable, 33% worsened and 17% improved over a median interval of 21.3 months (interquartile range 9.7–46.9 months).

Conclusion

DIPNECH occurs mostly in women and manifests diffuse pulmonary nodules and mosaic attenuation on imaging. It is commonly associated with airflow obstruction due to constrictive bronchiolitis, which manifests limited response to current pharmacological therapy.
Knockdown of LINC00665 inhibits proliferation and invasion of breast cancer via competitive binding of miR-3619-5p and inhibition of catenin beta 1
Authors: Lv Minhao , Mao Qixin , Li Juntao , Qiao Jianghua , Chen Xiuchun , Luo Suxia
Published: September 2020

Background

Long intergenic non-protein coding RNA00665 (LINC00665) plays a crucial tumorigenic role in many cancers, such as gastric cancer and lung adenocarcinoma. However, its role and mechanism of action in the progression of breast cancer (BC) are unknown.

Methods

LINC00665 expression levels were determined using quantitative polymerase chain reaction analysis with BC tissues and cell lines. BC cell proliferation was tested by performing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, whereas BC cell migration and invasion capabilities were analyzed by performing transwell migration assays. Percentages of apoptotic cells were measured by flow cytometry. Interactions between LINC00665 and miR-3169-5p were examined by performing luciferase reporter assays, and the expression levels of proteins, such as β-catenin, were examined by western blot analysis.

Results

LINC00665 was expressed at high levels in BC tissues and cells. Upregulated LINC00665 expression correlated with tumor size and tumor, node, and metastasis stages, but not with the age of patients. LINC00665 knockdown inhibited BC cell proliferation, migration, and invasion, whereas it promoted apoptosis. Moreover, bioinformatics analysis and the luciferase reporter assay revealed that LINC00665 bound the microRNA (miR) miR-3619-5p. miR-3619-5p expression correlated negatively with LINC00665 expression in BC tissues. miR-3619-5p overexpression inhibited BC cell proliferation, migration, and invasion, but promoted apoptosis. Simultaneous knockdown of LINC00665 and miR-3619-5p led to increased cell proliferation, migration, and invasion, and inhibited apoptosis. Additionally, catenin beta 1, which encodes the β-catenin protein, was the target gene of miR-3619-5p. β-catenin expression clearly decreased after LINC00665 knockdown and miR-3619-5p overexpression, but increased after simultaneous knockdown of LINC00665 and miR-3619-5p.

Conclusion

LINC00665 knockdown inhibited BC cell proliferation and invasion by binding miR-3619-5p and inhibiting β-catenin expression.
Rectifying Performance of Heterojunction Based on α-Borophene Nanoribbons with Edge Passivation
Authors: Yu Guoliang , Ding Wence , Xiao Xianbo , Li Xiaobo , Zhou Guanghui
Published: September 2020

We propose a planar model heterojunction based on α-borophene nanoribbons and study its electronic transport properties. We respectively consider three types of heterojunctions. Each type consists of two zigzag-edge α-borophene nanoribbons (Z αBNR), one is metallic with unpassivated or passivated edges by a hydrogen atom (1H-Z αBNR) and the other is semiconducting with the edge passivated by two hydrogen atoms (2H-Z αBNR) or a single nitrogen atom (N-Z αBNR). Using the first-principles calculations combined with the nonequilibrium Green’s function, we observe that the rectifying performance depends strongly on the atomic structural details of a junction. Specifically, the rectification ratio of the junction is almost unchanged when its left metallic ribbon changes from ZBNR to 1H-Z αBNR. However, its ratio increases from 120 to 240 when the right semiconducting one varies from 2H-Z αBNR to N-Z αBNR. This rectification effect can be explained microscopically by the matching degree the electronic bands between two parts of a junction. Our findings imply that the borophene-based heterojunctions may have potential applications in rectification nano-devices.
The impact of teach-back on patient recall and understanding of discharge information in the emergency department: the Emergency Teach-Back (EM-TeBa) study
Authors: Mahajan Mandhkani , Hogewoning Janine Alida , Zewald Jeroen Joseph Antonius , Kerkmeer Margreet , Feitsma Mathilde , van Rijssel Daphne Annika
Published: September 2020

Background

Previous research has demonstrated that patients leaving the emergency department (ED) have poor recall and understanding of their discharge information. The teach-back method is an easy technique that can be used to check, and if necessary correct, inaccurate recall. In our study, we aimed to determine the direct and short-term impact of teach-back as well as feasibility for routine use in the ED.

Methods

A prospective cohort study in an urban, non-academic ED was performed which included adult patients who were discharged from the ED with a new medical problem. The control group with the standard discharge was compared to the intervention group using the teach-back method. Recall and comprehension scores were assessed immediately after discharge and 2–4 days afterward by phone, using four standardized questions concerning their diagnosis, treatment, follow-up care, and return precautions.

Results

Four hundred eighty-three patients were included in the study, 239 in the control group, and 244 in the intervention group. Patients receiving teach-back had higher scores on all domains immediately after discharge and on three domains after 2–4 days (6.3% versus 4.5%). After teach-back, the proportion of patients that left the ED with a comprehension deficit declined from 49 to 11.9%. Deficits were most common for return precautions in both groups (41.3% versus 8.1%). Teach-back conversation took 1:39 min, versus an average of 3:11 min for a regular discharge interview.

Conclusion

Teach-back is an efficient and non-time-consuming method to improve patients’ immediate and short-term recall and comprehension of discharge information in the ED.
A web-based system for creating, viewing, and editing precursor mass spectrometry ground truth data
Authors: Henning Jessica , Smith Rob
Published: September 2020

Background

Mass spectrometry (MS) uses mass-to-charge ratios of measured particles to decode the identities and quantities of molecules in a sample. Interpretation of raw MS depends upon data processing algorithms that render it human-interpretable. Quantitative MS workflows are complex experimental chains and it is crucial to know the performance and bias of each data processing method as they impact accuracy, coverage, and statistical significance of the result. Creation of the ground truth necessary for quantitatively evaluating MS1-aware algorithms is difficult and tedious task, and better software for creating such datasets would facilitate more extensive evaluation and improvement of MS data processing algorithms.

Results

We present JS-MS 2.0, a software suite that provides a dependency-free, browser-based, one click, cross-platform solution for creating MS1 ground truth. The software retains the first version’s capacity for loading, viewing, and navigating MS1 data in 2- and 3-D, and adds tools for capturing, editing, saving, and viewing isotopic envelope and extracted isotopic chromatogram features. The software can also be used to view and explore the results of feature finding algorithms.

Conclusions

JS-MS 2.0 enables faster creation and inspection of MS1 ground truth data. It is publicly available with an MIT license at github.com/optimusmoose/jsms.
Intra-species variation within Lactobacillus rhamnosus correlates to beneficial or harmful outcomes: lessons from the oral cavity
Authors: Nadkarni Mangala A. , Deshpande Nandan P. , Wilkins Marc R. , Hunter Neil
Published: September 2020

Background

The origin of most of the Lactobacillus rhamnosus genome sequences lodged in NCBI can be traced to food and faecal isolates followed by blood and tissue sites but with minimal representation from oral and vaginal isolates. However, on the L. rhamnosus phylogenetic tree no apparent clade is linked to the origin of isolation or to the relevant clinical source, except for a distinct clade exclusively shared by L. rhamnosus isolates from early stages of dental pulp infection (LRHMDP2 and LRHMDP3) and from bronchoalveolar lavage (699_LRHA and 708_LRHA) from a critical care patient. These L. rhamnosus strains, LRHMDP2, LRHMDP3, 699_LRHA and 708_LRHA isolated from different continents, display closest genome neighbour gapped identity of 99.95%. The aim of this study was to define a potentially unique complement of genes of clinical relevance shared between these L. rhamnosus clinical isolates in comparison to probiotic L. rhamnosus strains.

Results

In this analysis we used orthologous protein identification tools such as ProteinOrtho followed by tblastn alignments to identify a novel tyrosine protein phosphatase (wzb)-tyrosine-protein kinase modulator EpsC (wzd)- synteny exopolysaccharide (EPS) cluster. This EPS cluster was specifically conserved in a clade of 5 clinical isolates containing the four L. rhamnosus clinical isolates noted above and Lactobacillus spp. HMSC077C11, a clinical isolate from a neck abscess. The EPS cluster was shared with only two other strains, L. rhamnosus BPL5 and BPL15, which formed a distant clade on the L. rhamnosus phylogenetic tree, with a closest genome neighbour gapped identity of 97.51% with L. rhamnosus LRHMDP2 and LRHMDP3.

Exclusivity of this EPS cluster (from those identified before) was defined by five EPS genes, which were specifically conserved between the clade of 5 clinical isolates and L. rhamnosus BPL5 and BPL15 when compared to the remaining L. rhamnosus strains. Comparative genome analysis between the clade of 5 clinical isolates and L. rhamnosus BPL5 and BPL15 showed a set of 58 potentially unique genes characteristic of the clade of 5.

Conclusion

The potentially unique functional protein orthologs associated with the clade of 5 clinical isolates may provide understanding of fitness under selective pressure.
Genome-wide association studies of ionomic and agronomic traits in USDA mini core collection of rice and comparative analyses of different mapping methods
Authors: Liu Shuai , Zhong Hua , Meng Xiaoxi , Sun Tong , Li Yangsheng , Pinson Shannon R. M. , Chang Sam K. C. , Peng Zhaohua
Published: September 2020

Background

Rice is an important human staple food vulnerable to heavy metal contamination leading to serious concerns. High yield with low heavy metal contamination is a common but highly challenging goal for rice breeders worldwide due to lack of genetic knowledge and markers.

Results

To identify candidate QTLs and develop molecular markers for rice yield and heavy metal content, a total of 191 accessions from the USDA Rice mini-core collection with over 3.2 million SNPs were employed to investigate the QTLs. Sixteen ionomic and thirteen agronomic traits were analyzed utilizing two univariate (GLM and MLM) and two multivariate (MLMM and FarmCPU) GWAS methods. 106, 47, and 97 QTLs were identified for ionomics flooded, ionomics unflooded, and agronomic traits, respectively, with the criterium of p-value < 1.53 × 10− 8, which was determined by the Bonferroni correction for p-value of 0.05. While 49 (~ 20%) of the 250 QTLs were coinciding with previously reported QTLs/genes, about 201 (~ 80%) were new. In addition, several new candidate genes involved in ionomic and agronomic traits control were identified by analyzing the DNA sequence, gene expression, and the homologs of the QTL regions. Our results further showed that each of the four GWAS methods can identify unique as well as common QTLs, suggesting that using multiple GWAS methods can complement each other in QTL identification, especially by combining univariate and multivariate methods.

Conclusions

While 49 previously reported QTLs/genes were rediscovered, over 200 new QTLs for ionomic and agronomic traits were found in the rice genome. Moreover, multiple new candidate genes for agronomic and ionomic traits were identified. This research provides novel insights into the genetic basis of both ionomic and agronomic variations in rice, establishing the foundation for marker development in breeding and further investigation on reducing heavy-metal contamination and improving crop yields. Finally, the comparative analysis of the GWAS methods showed that each method has unique features and different methods can complement each other.
Factors affecting the fruit and vegetable intake in Nepal and its association with history of self-reported major cardiovascular events
Authors: Nepali Sajama , Rijal Anupa , Olsen Michael Hecht , McLachlan Craig S. , Kallestrup Per , Neupane Dinesh
Published: September 2020

Background

The World Health Organization recommends consumption of a minimum of 400 g of fruits and vegetables per day for prevention of cardiovascular disease. Low fruit and vegetable intake is associated with an increased risk of stroke by 11% and ischemic heart disease by 31%. The present study aims to explore factors affecting the fruit and vegetable intake in Nepal and its association with history of self-reported major cardiovascular events (myocardial infarction and stroke).

Method

Data for this cross-sectional study were collected as part of the study “Community Based Management of Hypertension in Nepal” initiated in the Lekhnath Municipality in 2013. Demographic and nutrition information were collected using the WHO STEPwise approach to a surveillance tool. Descriptive statistics identified the frequency and percentage of fruit and vegetable intake. A Chi-square test examined the association between fruit and vegetable intake and history of self-reported cardiovascular events, socio-demographic and cardiovascular risk factors. Binary logistic regression analysis identified odds ratio with 95% confidence intervals between fruit and vegetable intake and history of self-reported cardiovascular events.

Results

The mean and median intake of fruits and vegetables were 3.3 ± 0.79 and 3 servings respectively. Of the 2815 respondents, 2% (59) reported having a history of major cardiovascular events. The adjusted odds of having a history of major cardiovascular events was 2.22 (95%CI, 1.06–4.66) for those who consumed < 3 servings compared to those who consumed ≥3 servings of fruits and vegetables a day.

Conclusion

The respondents who consumed < 3 servings of fruits and vegetables a day had higher odds of a history of major cardiovascular events in comparison to those who consumed ≥3 servings. This finding may carry a policy recommendation for those settings where the current recommendation of having ≥5 servings of fruits and vegetables a day is not possible. Our findings also suggest that surviving a major cardiovascular event was not enough in itself to modify nutritional intake. As many Nepali consumes low amount of fruits and vegetables, appropriate measures should be taken to increase this consumption to prevent cardiovascular morbidity and mortality.
Integrating trials into a whole-population cohort of children and parents: statement of intent (trials) for the Generation Victoria (GenV) cohort
Authors: Wake Melissa , Hu Yanhong Jessika , Warren Hayley , Danchin Margie , Fahey Michael , Orsini Francesca , Pacilli Maurizio , Perrett Kirsten P. , Saffery Richard , Davidson Andrew
Published: September 2020

Background

Very large cohorts that span an entire population raise new prospects for the conduct of multiple trials that speed up advances in prevention or treatment while reducing participant, financial and regulatory burden. However, a review of literature reveals no blueprint to guide this systematically in practice. This Statement of Intent proposes how diverse trials may be integrated within or alongside Generation Victoria (GenV), a whole-of-state Australian birth cohort in planning, and delineates potential processes and opportunities.

Methods

Parents of all newborns (estimated 160,000) in the state of Victoria, Australia, will be approached for two full years from 2021. The cohort design comprises four elements: (1) consent soon after birth to follow the child and parent/s until study end or withdrawal; retrospective and prospective (2) linkage to clinical and administrative datasets and (3) banking of universal and clinical biosamples; and (4) GenV-collected biosamples and data. GenV-collected data will focus on overarching outcome and phenotypic measures using low-burden, universal-capable electronic interfaces, with funding-dependent face-to-face assessments tailored to universal settings during the early childhood, school and/or adult years.

Results

For population or registry-type trials within GenV, GenV will provide all outcomes data and consent via traditional, waiver, or Trials Within Cohorts models. Trials alongside GenV consent their own participants born within the GenV window; GenV may help identify potential participants via opt-in or opt-out expression of interest. Data sharing enriches trials with outcomes, prior data, and/or access to linked data contingent on custodian’s agreements, and supports modeling of causal effects to the population and between-trials comparisons of costs, benefits and utility. Data access will operate under the Findability, Accessibility, Interoperability, and Reusability (FAIR) and Care and Five Safes Principles. We consider governance, ethical and shared trial oversight, and expectations that trials will adhere to the best practice of the day.

Conclusions

Children and younger adults can access fewer trials than older adults. Integrating trials into mega-cohorts should improve health and well-being by generating faster, larger-scale evidence on a longer and/or broader horizon than previously possible. GenV will explore the limits and details of this approach over the coming years.
Knowledge, attitudes, and practices of primary health care physicians regarding the pre-travel counselling of patients with type 2 diabetes in Riyadh, Saudi Arabia
Authors: Alduraibi Rabia Khalid , Almigbal Turky H. , Alrasheed Abdullah A. , Batais Mohammed Ali
Published: September 2020

Background

Travel has become an integral part of Saudi life. People with diabetes face many challenges while travelling that can have detrimental effects on glycaemic control. However, no previous studies have investigated pre-travel counselling in Saudi Arabia. This study aims to assess the knowledge, attitudes and practices of primary health care (PHC) physicians regarding pre-travel counselling for patients with type 2 diabetes.

Methods

This cross-sectional study was conducted in PHC centres under the Ministry of Health in Riyadh, Saudi Arabia, during the period 2018–2019. A cluster multistage random sampling technique was used to recruit physicians. The data were collected through a self-administered questionnaire.

Results

Three hundred and eighty-five primary health care physicians were recruited. This study showed that more than half (57.9%) of PHC physicians had poor knowledge scores. Additionally, the following characteristics were significantly associated with poor knowledge: being younger in age, being male, being Saudi, being a general practitioner, and having limited (0–5 years) experience. A total of 183 (47.5%) subjects showed disagreement attitudes towards the importance of pre-travel counselling among patients with diabetes. Furthermore, these disagreement attitudes were significantly associated with being older and having more years of experience. The majority (62.6%) of the physicians had poor practice scores. Poor practices were detected among physicians who were younger, male, and Saudi and who had a general practitioner specialty and degree.

Conclusions

It could be concluded that a gap was detected in the knowledge and practices of primary health care physicians regarding pre-travel counselling for people with type 2 diabetes. Therefore, it is necessary to create easily accessible travel medicine education programmes for Saudi PHC providers to improve the management of travellers with diabetes.
Mechanical Thrombectomy of COVID-19 positive acute ischemic stroke patient: a case report and call for preparedness
Authors: Mansour Ossama Yassin , Malik Amer M. , Linfante Italo
Published: September 2020

Background

The novel coronavirus (COVID-19) global pandemic is associated with an increased incidence of acute ischemic stroke (AIS) secondary to large vessel occlusion (LVO). The treatment of these patients poses unique and significant challenges to health care providers requiring changes in existing protocols.

Case presentation

A 54-year-old COVID-19 positive patient developed sudden onset left hemiparesis secondary to an acute right middle cerebral artery occlusion (National Institutes of Health Stroke Scale (NIHSS) score = 11). Mechanical thrombectomy (MT) was performed under a new protocol specifically designed to maximize protective measures for the team involved in the care of the patient. Mechanical Thrombectomy was performed successfully under general anesthesia resulting in TICI 3 recanalization. With regards to time metrics, time from door to reperfusion was 60 mins. The 24-h NIHSS score decreased to 2. Patient was discharged after 19 days after improvement of her pulmonary status with modified Rankin Scale = 1.

Conclusion

Patients infected by COVID-19 can develop LVO that is multifactorial in etiology. Mechanical thrombectomy in a COVID-19 confirmed patient presenting with AIS due to LVO is feasible with current mechanical thrombectomy devices. A change in stroke workflow and protocols is now necessary in order to deliver the appropriate life-saving therapy for COVID-19 positive patients while protecting medical providers.
An immunotherapy effect analysis in Rasmussen encephalitis
Authors: Liba Zuzana , Vaskova Martina , Zamecnik Josef , Kayserova Jana , Nohejlova Hana , Ebel Matyas , Sanda Jan , Ramos-Rivera Gonzalo Alonso , Brozova Klara , Liby Petr , Tichy Michal , Krsek Pavel
Published: September 2020

Background

Immune-mediated mechanisms substantially contribute to the Rasmussen encephalitis (RE) pathology, but for unknown reasons, immunotherapy is generally ineffective in patients who have already developed intractable epilepsy; overall laboratory data regarding the effect of immunotherapy on patients with RE are limited. We analyzed multiple samples from seven differently treated children with RE and evaluated the effects of immunotherapies on neuroinflammation. Immunotherapy was introduced to all patients at the time of intractable epilepsy and they all had to undergo hemispherothomy.

Methods

Immunohistochemistry, flow cytometry, Luminex multiplex bead and enzyme-linked immunosorbent assay techniques were combined to determine: 1) inflammatory changes and lymphocyte subpopulations in 45 brain tissues; 2) lymphocyte subpopulations and the levels of 12 chemokines/cytokines in 24 cerebrospinal fluid (CSF) samples and 30 blood samples; and 3) the dynamics of these parameters in four RE patients from whom multiple samples were collected.

Results

Sustained T cell-targeted therapy with cyclophosphamide, natalizumab, alemtuzumab, and intrathecal methotrexate (ITMTX), but not with azathioprine, substantially reduced inflammation in brain tissues. Despite the therapy, the distributions of CD8+ T cells and the levels of C-X-C motif ligand (CXCL) 10, CXCL13, and B cell activating factor (BAFF) in patients’ CSF remained increased compared to controls. A therapeutic approach combining alemtuzumab and ITMTX was the most effective in producing simultaneous reductions in histopathological inflammatory findings and in the numbers of activated CD8+ T cells in the brain tissue, as well as in the overall CD8+ T cell population and chemokine/cytokine production in the CSF.

Conclusions

We provide evidence that various T cell-targeted immunotherapies reduced inflammation in the brains of RE patients. The observation that intractable epilepsy persisted in all of the patients suggests a relative independence of seizure activity on the presence of T cells in the brain later in the disease course. Thus, new therapeutic targets must be identified. CXCL10, CXCL13 and BAFF levels were substantially increased in CSF from all patients and their significance in RE pathology remains to be addressed.