bluuebunny/crossref_metadata_2025 huggingface dataset:
Defining prognosis in sarcoidosis
Authors: Lopes Mariana Carneiro , Amadeu Thaís Porto , Ribeiro-Alves Marcelo , Costa Claudia Henrique da , Silva Bruno Rangel Antunes , Rodrigues Luciana Silva , Bessa Elisabeth Jauhar Cardoso , Bruno Leonardo Palermo , Lopes Agnaldo José , Rufino Rogerio
Published: November 2020

Sarcoidosis is a multi-systemic granulomatous disease. Affected individuals can show spontaneous healing, develop remission with drug treatment within 2 years, or become chronically ill. Our main goal was to identify features that are related to prognosis.

The study consisted of 101 patients, recruited at a single center, who were already diagnosed with sarcoidosis at the start of the study or were diagnosed within 48 months. Ninety individuals were followed-up for at least 24 months and were classified according to clinical outcome status (COS 1 to 9). Those with COS 1–4 and COS 5–9 were classified as having favorable and unfavorable outcomes, respectively. Unconditional logistic regression analyses were conducted to define which variables were associated with sarcoidosis outcomes. Subsequently, we established a scoring system to help predict the likelihood of a favorable or unfavorable outcome.

Of our patients, 48% developed a chronic form of the disease (COS 5–9). Three clinical features were predictive of prognosis in sarcoidosis. We built a score-based model where the absence of rheumatological markers (1 point), normal pulmonary functions (2 points), and the presence of early respiratory symptoms manifestations (2 points) were associated with a favorable prognosis. We predicted that a patient with a score of 5 had an 86% (95% confidence interval [CI] 74%–98%) probability of having a favorable prognosis, while those with scores of 4, 3, 2, 1, and 0 had probabilities of 72% (95% CI 59–85%), 52% (95% CI 40–63%), 31% (95% CI 17–44%), 15% (95% CI 2–28%), and 7% (95% CI 0–16%) of having a favorable prognosis, respectively. Thus, our easy-to-compute algorithm can help to predict prognosis of sarcoidosis patients, facilitating their management.
Psychological nursing intervention on anxiety and depression in patients with urinary incontinence after radical prostatectomy
Authors: Yang Liying , Ling Danjuan , Ye Lanfen , Zeng Manping
Published: November 2020

Background:

Prostate cancer (PC) is one of the most familiar disease of the male reproductive system globally. In treating the clinically localized PC, the radical prostatectomy is regarded as a gold standard, but it is associated with syndromes as urinary incontinence (UI), which can have a significant impact on patients’ quality of life. Nurse takes responsibility in the management of the UI for their convenience compared with doctors to contact with patients and build better trust relationships with survivals. However, most of the studies focus on the physiological level, the psychological nursing intervention research is less. The purpose of the trial is to introduce a psychological intervention program and to study its effects on anxiety and depression after prostatectomy in IU patients.

Methods:

This is a single-center randomized controlled trial that was authorized by Ethics Committee of the First People's Hospital of Chenzhou City (2020054). One hundred participants who undergo radical prostatectomy are analyzed. Inclusion criteria are the following: PC is diagnosed based on histological results; Participants in the study voluntarily sign the informed consent table; Severe UI after extubation; Patients with postoperative UI do not receive any drug treatment. Exclusion criteria are the followings: patients with the history of prostate operation; patients with the history of severe renal and liver malignancy; UI caused by reasons other than prostatectomy. The main outcomes are the degree of anxiety and depression 2 months after urinary catheter is removed. The secondary outcomes are the quality of life 2 months after urinary catheter is removed. All data are collected and analyzed by the Social Science software version 21.0 (SPSS, Inc., Chicago, IL) program.

Results:

The relevant indexes of severe UI patients are compared in the table.

Conclusion:

Psychological nursing intervention may have a positive effect on depression and anxiety in the UI patients after receiving the radical prostatectomy.
Low-site versus traditional peritoneal dialysis catheterization
Authors: Gong Lifeng , Xu Wei , Tang Weigang , Lu Jingkui , Li Yani , Jiang Huaqin , Li Hui
Published: November 2020

Background:

The objective of this study was to compare the complications of low-site peritoneal dialysis (PD) catheter placement and traditional open surgery in peritoneal dialysis catheter insertion.

Methods:

The following databases were searched from inception to September 6, 2019: PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure, and Wanfang. Eligible studies comparing low-site PD catheter placement and traditional open surgery in peritoneal dialysis catheter insertion were included. The data were analyzed using Review Manager Version 5.3.

Results:

Seven studies were included in the meta-analysis. A total of 504 patients were included in the low-site PD catheter placement group, and 325 patients were included in the traditional open surgery group. Compared with traditional open surgery, low-site PD catheter placement had a lower incidence rate of catheter displacement (odds ratios [OR] 0.11, 95% CI 0.05–0.22, P < .01) and noncatheter displacement dysfunction (OR 0.11, 95% CI 0.04–0.31, P < .01). However, there was no difference between the 2 catheter insertion methods concerning bleeding (OR 0.53, 95% CI 0.23–1.22, P = .13), PD fluid leakage (OR 0.40, 95% CI 0.15–1.10, P = .07), hypogastralgia (OR 0.95, 95% CI 0.32–2.80, P = .93), peritonitis (OR 0.70, 95% CI 0.32–1.54, P = .38), or exit-site and tunnel infections (OR 0.39, 95% CI 0.14–1.03, P = .06).

Conclusion:

Low-site PD catheter placement reduced the risk of catheter displacement and noncatheter displacement dysfunction and did not increase the risk of bleeding, PD fluid leakage, hypogastralgia, peritonitis, or exit site and tunnel infections. Additional large multicenter randomized controlled trials are needed to confirm these conclusions.
Heart rate variability and inflammatory bowel disease in humans
Authors: Kim Kyu-Nam , Yao Yao , Ju Sang-Yhun
Published: November 2020

The autonomic nervous system (ANS) maintains homeostasis in the gastrointestinal tract, including immunity, inflammation and motility, through the brain-gut axis. To date, the associations between ANS function and inflammatory bowel disease (IBD) have been controversial and inconclusive in human studies. PubMed, Cochrane Library, and Embase were searched through February 2020 for articles reporting these association between heart rate variability (HRV), an indirect measure of ANS activity, and IBD. The standardized mean differences and 95% confidence intervals (CIs) were calculated. Ten eligible studies involving 273 ulcerative colitis patients, 167 Crohn's disease patients and 208 healthy controls were included. The values of the total power (SMD = −0.83, 95% CI = −1.44, −0.21), high frequency (SMD = −0.79, 95% CI = −1.20, −0.38), RR interval (SMD = −0.66, 95% CI = −1.04, −0.27), standard deviation of the RR intervals (SMD = −1.00, 95% CI = −1.73, −0.27), percentage of RR intervals with a greater than 50-millisecond variation (SMD = −0.82, 95% CI = −1.33, −0.30) and the square root of the mean squared differences in successive RR intervals (SMD = −0.71, 95% CI = −1.15, −0.26) of the IBD patients were lower than those of the healthy controls, and moderate to large effect sizes were observed in all HRV indices, except for low frequency (SMD = −0.41, 95% CI = 0.95, 0.13). IBD was strongly associated with an overall decrease in HRV, indicating substantially decreased ANS activity. Furthermore, the parasympathetic nerve displayed a stronger inverse association with ANS activity than the sympathetic nerve, indicating ANS dysfunction in patients with IBD.
Mesonephric-like adenocarcinoma of the ovary
Authors: Chen Qiuhe , Shen Yangmei , Xie Chuan
Published: November 2020

Rationale:

Mesonephric-like adenocarcinoma (MLA) from ovary is a very rare tumor which derives from mesonephric duct remnant of the female genital tract. Only six cases have been reported so far in the English literature.

Patient concerns:

A 29-year-old female patient was referred to the local hospital with a 20-day history of abdominal discomfort.

Diagnoses:

Pelvic ultrasound examination revealed a solid and cystic mass measuring 10 cm in diameter in the right adnexal area and a cystic mass measuring 5 cm in the left adnexal area. Postoperative pathology in the local hospital revealed suspected malignancy of the right ovary, and she was then transferred to our institution for definite diagnosis. The tumor mass was finally diagnosed as a primary MLA arising from the right ovary by histological and immunohistochemical examination in our institution.

Interventions:

The patient underwent laparoscopic right adnexectomy and removal of left ovarian cyst in the local institution. Then, she underwent a complete staging surgery including a total hysterectomy, left adnexectomy, pelvic plus para-aortic lymphadenectomy, and omentectomy in our hospital. In addition, she received four cycles of combination chemotherapy with carboplatin plus paclitaxel.

Outcomes:

There is no evidence of recurrence with 13 months of follow-up till now, and we are still following-up this patient.

Lessons:

MLA is an extremely uncommon malignancy with difficult diagnosis, unclear treatment and poor prognosis. Familiarizing with the clinical features and optimal management of this rare tumor may increase awareness of the disease among clinicians and pathologists, thus avoiding the misdiagnosis and mistreatment.
Chinese herbal medicine Yanghe decoction for ankylosing spondylitis
Authors: Xu Xiaosheng , Chen Hong , Yuan Xiaoping , Wan Yi , Gong Liangjin , Ma Zeren , Xu Tao
Published: November 2020

Background:

Chinese herbal medicine is a commonly used traditional treatment for ankylosing spondylitis (AS). Among them, Yanghe decoction (YHD) has an obvious effect in relieving the symptoms of AS, but its efficacy is still controversial. The purpose of this study is to systematically evaluate the effectiveness and safety of YHD in the treatment of AS patients.

Methods:

From the establishment to September 2020, we will search a total of 7 electronic databases including PubMed, Cochrane Library, Embase, CNKI, VIP, WanFang, and the Chinese SinoMed Database. Two independent reviewers will search the database for relevant randomized controlled trials (RCTs), extract data, and evaluate the quality of the included RCTs. Data analysis will be processed by RevMan V.5.4 software.

Results:

The results of this systematic review will be published in a peer-reviewed journal.

Conclusion:

This study will provide evidence for the effectiveness of YHD in treating patients with AS.
Sex-differences in determinants of suicide risk preceding psychiatric admission: An electronic medical record study
Authors: McQuaid Robyn J. , Nikolitch Katerina , Vandeloo Katie L. , Burhunduli Patricia , Phillips Jennifer L.
Published: November 2020

Using electronic medical record (EMR) data collected from psychiatric inpatient admissions, the objective of this study was to identify sex differences in risk factors for presence of suicide plans and/or attempts within the 30 days preceding hospital admission. Resident Assessment Instrument for Mental Health (RAI-MH) intake data were obtained for patients admitted to a Canadian tertiary-care hospital deemed a ‘threat or danger to self’ during a ten-year period (2008-2018). Data was extracted for individuals categorized into three groups: non-suicidal (N=568), presence of suicide plan (N=178), and presence of suspected suicide attempt (N=124) in the 30 days prior to hospital admission. A multivariate logistic regression revealed that younger age (odds ratio=0.97), female sex (OR=1.56), disrupted family relationships (OR=1.54), recent stressors (OR=1.59), participation in social activities (OR=1.54), having no confidant (OR=1.55), and diagnosis of depressive disorder (OR=5.54) increased the odds of suicide plan and/or attempt in the 30 days prior to hospital admission. Stratifying the regression model by sex highlighted different risk factors for suicide plan and attempt specific to males and females. EMR-derived findings highlight psychosocial and clinical determinants associated with suicide plan or attempt prior to psychiatric admission that differ according to sex.
Typhoon Eye Effect vs. Ripple Effect: The Role of Family Size on the Mental Health under the COVID-19 Pandemic in Pakistan
Authors: Lateef Tooba , Chen Jiyao , Tahir Muhammad , Lateef Teba Abdul , Chen Bryan , Li Jizhen , Zhang Stephen X.
Published: November 2020

Background

The recent outbreak of COVID-19 impacts the mental health of people worldwide. The mental conditions and the associated predictors of adults in Pakistan, the fifth most populous country in the world, during the COVID-19 remains understudied. We aim to investigate distress, anxiety and overall mental health and their associated predictors among Pakistani adults in this pandemic. We specifically examine the mental health issues based on the distance to the epicenter, a predictor that has revealed opposing evidence in other countries based on the theories of typhoon eye effect and ripple effect. The samples consist of 601 adults who were surveyed online about 2.5 months into the outbreak across Pakistan with varying distance to the epicenter of COVID-19 of Karachi in Pakistan.

Results

The results showed that 9.2% and 19.0% of the participants surpassed the cut-off of distress and anxiety disorders, respectively. Overall, the distance to the epicenter positively predicted the mental health of adults in Pakistan, and family size negatively moderated this effect. The distance to the epicenter negatively predicted distress and anxiety disorders for adults in large families, which are quite common in Pakistan.

Conclusion

The evidence of the study interestingly finds the prediction of the mental health of people by their distance to the epicenter depends on the family. The evidence of this study can help to provide the initial indicator for mental health care providers to screen vulnerable groups in Pakistan, a populous country that continues to struggle to cope with the COVID-19 pandemic.
Viruses such as SARS-CoV-2 can be partially shielded from UV radiation when in particles generated by sneezing or coughing: Numerical simulations
Authors: Doughty David C. , Hill Steven C. , Mackowski Daniel W.
Published: November 2020

UV radiation can inactivate viruses such as SARS-CoV-2. However, designing effective UV germicidal irradiation (UVGI) systems can be difficult because the effects of dried respiratory droplets and other fomites on UV light intensities are poorly understood. Numerical modeling of UV intensities inside virus-containing particles on surfaces can increase understanding of these possible reductions in UV intensity. We model UV intensities within spherical approximations of virions randomly positioned within spherical particles. The model virions and dried particles have sizes and optical properties to approximate SARS-CoV-2 and dried particles formed from respiratory droplets, respectively. Wavelengths used are 260 nm (germicidal UVC) and 302 nm (solar UVB). In 5- and 9-μm diameter particles on a surface, illuminated by 260-nm UV light from a direction perpendicular to the surface, 10% and 18% (respectively) of simulated virions are exposed to intensities less than 1/100thof intensities in individually exposed virions (i.e., they are partially shielded). Even for 302-nm light, where the absorption is small, 11% of virions in 9-µm particles have exposures 1/100ththose of individually exposed virions. Calculated results show that shielding of virions in a particle can be strongly reduced by illuminating a particle either from multiple widely separated incident directions, or by illuminating a particle rotating in air (because of turbulence, Brownian diffusion, etc.) for a time sufficient to rotate through all orientations with respect to the UV illumination. Because highly UV-reflective paints and surfaces can increase the angular ranges of illumination, they appear likely to be useful for reducing shielding of virions.
Association of HLA class I genotypes with age at death of COVID-19 patients
Authors: Shkurnikov Maxim , Nersisyan Stepan , Jankevic Tatjana , Galatenko Alexei , Gordeev Ivan , Vechorko Valery , Tonevitsky Alexander
Published: November 2020

Background

HLA class I molecules play a crucial role in the development of a specific immune response to viral infections by presenting viral peptides to cell surface where they will be further recognized by T cells. In the present manuscript we explored whether HLA class I genotype can be associated with critical course of COVID-19 by searching possible connections between genotypes of deceased patients and their age at death.

Methods and Findings

HLA-A, HLA-B and HLA-C genotypes of n = 111 deceased patients with COVID-19 (Moscow, Russia) and n = 428 volunteers were identified with targeted next-generation sequencing. Deceased patients were splitted into two groups according to age at death: n = 26 adult patients with age at death below 60 completed years (inclusively) and n = 85 elderly patients over 60. With the use of HLA class I genotypes we developed a risk score which is associated with the ability to present SARS-CoV-2 peptides by an individual’s HLA class I molecule set. The resulting risk score was significantly higher in the group of deceased adults compared to elderly adults (p = 0.00348, AUC ROC = 0.68). In particular, presence of HLA-A*01:01 allele was associated with high risk, while HLA-A*02:01 and HLA-A*03:01 mainly contributed to the low risk group. The analysis of homozygous patients highlighted the results even stronger: homozygosity by HLA-A*01:01 mainly accompanied early deaths, while only one HLA-A*02:01 homozygote died before 60.

Conclusions

The obtained results suggest the important role of HLA class I peptide presentation in the development of a specific immune response to COVID-19. While prediction of age at death by HLA class I genotype had a reliable performance, involvement of HLA class II genotype can make it even higher in the future studies.
Statistical techniques to estimate the SARS-CoV-2 infection fatality rate
Authors: Mieskolainen M. , Bainbridge R. , Buchmueller O. , Lyons L. , Wardle N.
Published: November 2020

Abstract

The determination of the infection fatality rate (IFR) for the novel SARS-CoV-2 coronavirus is a key aim for many of the field studies that are currently being undertaken in response to the pandemic. The IFR together with the basic reproduction numberR0, are the main epidemic parameters describing severity and transmissibility of the virus, respectively. The IFR can be also used as a basis for estimating and monitoring the number of infected individuals in a population, which may be subsequently used to inform policy decisions relating to public health interventions and lockdown strategies. The interpretation of IFR measurements requires the calculation of confidence intervals. We present a number of statistical methods that are relevant in this context and develop an inverse problem formulation to determine correction factors to mitigate time-dependent effects that can lead to biased IFR estimates. We also review a number of methods to combine IFR estimates from multiple independent studies, provide example calculations throughout this note and conclude with a summary and “best practice” recommendations. The developed code is available online.
Testing-on-a-probe biosensors reveal association of early SARS-CoV-2 total antibodies and surrogate neutralizing antibodies with mortality in COVID-19 patients
Authors: Yang He S. , Racine-Brzostek Sabrina E. , Karbaschi Mohsen , Yee Jim , Dillard Alicia , Steel Peter A.D. , Lee William T. , McDonough Kathleen A. , Qiu Yuqing , Ketas Thomas J. , Francomano Erik , Klasse P. J. , Hatem Layla , Westblade Lars , Wu Heng , Chen Haode , Zuk Robert , Tan Hong , Girardin Roxanne C. , Dupuis Alan P. , Payne Anne F. , Moore John P. , Cushing Melissa M. , Chadburn Amy , Zhao Zhen
Published: November 2020

The association of mortality with early humoral response to SARS-CoV-2 infection within the first few days after onset of symptoms (DAOS) has not been thoroughly investigated partly due to a lack of sufficiently sensitive antibody testing methods. Here we report two sensitive and automated testing-on-a-probe (TOP) biosensor assays for SARS-CoV-2 viral specific total antibodies (TAb) and surrogate neutralizing antibodies (SNAb), which are suitable for clinical use. The TOP assays employ an RBD-coated quartz probe using a Cy5-Streptavidin-polysacharide conjugate to improved sensitivity and minimize interference. Disposable cartridge containing pre-dispensed reagents requires no liquid manipulation or fluidics during testing. The TOP-TAb assay exhibited higher sensitivity in the 0-7 DAOS window than a widely used FDA-EUA assay. The rapid (18 min) and automated TOP-SNAb correlated well with two well-established SARS-CoV-2 virus neutralization tests. The clinical utility of the TOP assays was demonstrated by evaluating early antibody responses in 120 SARS-CoV-2 RT-PCR positive adult hospitalized patients. Higher baseline TAb and SNAb positivity rates and more robust antibody responses were seen in patients who survived COVID-19 than those who died in the hospital. Survival analysis using the Cox Proportional Hazards Model showed that patients who were TAb and SNAb negative at initial hospital presentation were at a higher risk of in-hospital mortality. Furthermore, TAb and SNAb levels at presentation were inversely associated with SARS-CoV-2 viral load based on concurrent RT-PCR testing. Overall, the sensitive and automated TAb and SNAb assays allow detection of early SARS-CoV-2 antibodies which associate with mortality.
Age-related clonal haematopoiesis is more prevalent in older adults with HIV: the ARCHIVE study
Authors: Dharan Nila J. , Yeh Paul , Bloch Mark , Yeung Miriam , Baker David , Guinto Jerick , Roth Norm , Ftouni Sarah , Ognenovska Katherine , Smith Don , Hoy Jennifer F. , Woolley Ian , Pell Catherine , Templeton David J. , Fraser Neil , Rose Nectarios , Hutchinson Jolie , Petoumenos Kathy , Dawson Sarah-Jane , Polizzotto Mark N. , Dawson Mark A. ,   for the ARCHIVE Study Group
Published: November 2020

People with HIV have higher rates of certain comorbidities, particularly cardiovascular disease and some malignancies, than people without HIV. As somatic mutations associated with age-related clonal haematopoiesis (CH) are linked to similar comorbidities in the general population, we hypothesized that CH may be more prevalent in people with HIV. To address this issue, we established a prospective cohort study recruiting 220 HIV-positive and 226 HIV-negative participants aged 55 years or older in Australia. Demographic characteristics, clinical data and peripheral blood were collected to assess for the presence of CH mutations and identify potential risk factors for and clinical sequelae of CH. Investigators testing for CH were blinded to participants’ HIV status. In total, 132 CH mutations were identified in 99 (22.2%) of 446 participants. CH was more prevalent in HIV-positive participants than HIV-negative participants (27.7% vs. 16.8%, p =0.006), overall and across all age groups. HIV infection was associated with an increased odds of having CH (adjusted odds ratio 2.10, 95% confidence interval 1.30-3.38, p=0.002). The most common genes mutated wereDNMT3A(48.5%),TET2(20.5%) andASXL1(11.4%). CH and HIV infection were independently associated with increases in blood parameters and biomarkers associated with inflammation. These data suggest a selective advantage for the emergence of CH in the context of chronic infection and inflammation related to HIV infection.
Comparing COVID-19 and influenza presentation and trajectory
Authors: Benaim Anat Reiner , Sobel Jonathan Aryeh , Almog Ronit , Lugassy Snir , Shabbat Tsviel Ben , Johnson Alistair , Eytan Danny , Behar Joachim A.
Published: November 2020

Background

COVID-19 is a newly recognized illness with a predominantly respiratory presentation. It is important to characterize the differences in disease presentation and trajectory between COVID-19 patients and other patients with common respiratory illnesses. These differences can enhance knowledge of pathogenesis and help in guiding treatment.

Methods

Data from electronic medical records were obtained from individuals admitted with respiratory illnesses to Rambam Health Care Campus, Haifa, Israel, between October 1st, 2014 and October 1st, 2020. Four groups of patients were defined: COVID-19 (693), influenza (1,612), severe acute respiratory infection (SARI) (2,292) and Others (4,054). The variable analyzed include demographics (7), vital signs (8), lab tests (38),and comorbidities (15) from a total of 8,651 hospitalized adult patients. Statistical analysis was performed on biomarkers measured at admission and for their disease trajectory in the first 48 hours of hospitalization, and on comorobidity prevalence.

Results

COVID-19 patients were overall younger in age and had higher body mass index, compared to influenza and SARI. Comorbidity burden was lower in the COVID-19 group compared to influenza and SARI. Severely- and moderately-ill COVID-19 patients older than 65 years of age suffered higher rate of in-hospital mortality compared to hospitalized influenza patients. At admission, white blood cells and neutrophils were lower among COVID-19 patients compared to influenza and SARI patients, while pulse rate and lymphoctye percentage were higher. Trajectories of variables during the first two days of hospitalization revealed that white blood count, neutrophils percentage and glucose in blood increased among COVID-19 patients, while decreasing among other patients.

Conclusions

The intrinsic virulence of COVID-19 appeared higher than influenza. In addition, several critical functions, such as immune response, coagulation, heart and respiratory function and metabolism were uniquely affected by COVID-19.
The Algerian chapter of SARS-CoV-2 pandemic: An evolutionary, genetic, and epidemiological prospect of the first wave
Authors: Zeghbib Safia , Somogyi Balázs , Zana Brigitta , Kemenesi Gábor , Herczeg Róbert , Derrar Fawzi , Jakab Ferenc
Published: November 2020

To explore the SARS-CoV-2 early pandemic in Algeria, a dataset comprising forty-three genomes originating from SARS-CoV-2 sampled from Algeria and other countries worldwide, from 24 December 2019 through 8 March 2020, of which, were thoroughly examined. While performing a multi-component analysis regarding the Algerian outbreak, the toolkit of phylogenetic, phylodynamic, haplotype analyses and genomic analysis were effectively implemented. We estimated the TMRCA in reference to the Algerian pandemic and highlighted both the introduction of the disease originating in France and the missing data depicted in the transmission loop. Most importantly, we unveiled mutational patterns, recombination events and the relatedness regarding the Algerian sequences to the dataset. Our results revealed the unique amino-acid replacement L129F in the orf3a gene in Algeria_EPI_ISL_418241. Additionally, a connection between Algeria_EPI_ISL_420037 and sequences originating from the USA was observed through a USA characteristic amino-acid replacement T1004I in the nsp3 gene, found in the aforementioned Algerian sequence. Lastly, we assessed the Algerian mitigation measures regarding disease containment using statistical analyses.

Author summary

A novel human coronavirus, specifically SARS-CoV-2, emerged in China in late 2019. In Algeria, the contact tracing revealed the introduction of the disease originated in France, however, the intricate dynamics regarding the disease remain unexplored. In this study, we attempt to portray our perspective regarding the evolutionary, genetic and epidemiological aspects of the early pandemic in Algeria during the spring of 2020, through the use of time scaled phylogeny, phylodynamic and mutational pattern characterization and exploration. Additionally, we assessed the efficiency of the implemented mitigation measures using statistical analysis. The results supported the virus introduction from France and highlighted an Algerian characteristic amino-acid replacement in addition to a relatedness to the USA sequences. Moreover, we revealed an indirect contamination among the three sampled patients. Therefore, our analysis is a starting point for further investigations and emphasize the importance regarding intensive sequencing and genome exploration for mitigation measures implementation, and both drug and vaccine development.
Eip74EF is a dominant modifier for ALS-FTD linked mutant VCP phenotypes inDrosophila, but not miR-34
Authors: Chalmers Madeleine R. , Kim JiHye , Kim Nam Chul
Published: November 2020

In 2012 Liuet al. reported that miR-34 is an age-related miRNA regulating age-associated events and long-term brain integrity inDrosophila. They demonstrated that modulating miR-34 and its downstream target Eip74EF showed beneficial effects on age-related diseases using aDrosophilamodel of SCA3trQ78. These results imply that miR-34 could be a general genetic modifier and therapeutic candidate for age-related diseases. Therefore, we examined the effect of miR-34 and Eip74EF on another age-relatedDrosophiladisease model. Using aDrosophilamodel expressing mutantDrosophilaVCP that causes amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), or multisystem proteinopathy (MSP), we demonstrated that abnormal eye phenotypes generated byDrosophilaVCP R152H were rescued when expressed with Eip74EF siRNA. Contrary to our expectation, miR-34 overexpression resulted in lethality when expressed with mutant VCP. Our data indicate that the other downstream targets of miR-34 might more significantly interact with mutant VCP, causing lethality. Identifying transcriptional targets of Eip74EF might provide valuable insights into diseases caused by mutations in VCP such as ALS, FTD, and MSP.
Spatial arrangement and biofertilizers enhance the performance of legume – millet intercropping system in rainfed areas of southern India
Authors: Singh Devesh , Mathimaran Natarajan , Sekar Jegan , Ramalingam Prabavathy Vaiyapuri , Perisamy Yuvaraj , Raju Kathiravan , Raj Rengalakshmi , King Israel Oliver , Nanjundegowda Thimmegowda Matadadoddi , Narayanswamy Manjunatha Baiyapalli , Chikkegowda Bhavitha Nayakanahalli , Siddegowda Savitha Matakere , Bagyaraj Davis Joseph , Mäder Paul , Boller Thomas , Kahmen Ansgar
Published: November 2020

Biofertilization via the inoculation with arbuscular mycorrhizal fungi (AMF), combined with rhizobia and plant growth promoting rhizobacteria (PGPR), are beginning to become established as an effective and sustainable measure to improve yields. Biofertilization might have a particular potential to boost the yield of intercropping systems in rainfed areas because AMF can form a common mycorrhizal network (CMN) that can transfer nutrients and water between two plants and balance as such belowground competition. In this study, we tested if biofertilizers can enhance the yield of intercropping systems using a pigeon pea (PP) – finger millet (FM) intercropping system grown for two consecutive growing seasons (2016/17 and 2017/18) at two contrasting sites in Bengaluru and Kolli Hills, India. To validate the process of bioirrigation (transfer of water between rhizosphere of two plants), we tested, for the first time, if the spatial arrangement of intercropped plants using either a row-wise or a mosaic design affected yield and water relations with and without biofertilizers. Our results demonstrate that intercropping can improve the straw and grain yield in PP–FM intercropping compared to the respective monocultures but that intercropping effects vary depending on the site characteristic such as climate and soil type. Spatial arrangement of component plants affected the total, straw and grain biomass in intercropping treatments, but this effect also varied across sites. Most importantly, the results from the 2017-18 growing season clearly demonstrated a positive effect of biofertilizer on biomass yield, and this effect was irrespective of site, spatial arrangement, mixed or monoculture. Despite a yield increase in intercropping, we did not see a positive effect of biofertilization on water relations of FM possibly due to interspecific competition for soil moisture where PP dominated. In summary, our study shows the potential of biofertilizers to increase the yield of intercropping systems in rainfed dryland agriculture.
A history of previous childbirths is linked to women’s white matter brain age in midlife and older age
Authors: Voldsbekk Irene , Barth Claudia , Maximov Ivan I. , Kaufmann Tobias , Beck Dani , Richard Geneviève , Moberget Torgeir , Westlye Lars T. , de Lange Ann-Marie G.
Published: November 2020

Maternal brain adaptations occur in response to pregnancy, but little is known about how parity impacts white matter (WM) and WM ageing trajectories later in life. Utilising global and regional brain-age prediction based on multi-shell diffusion MRI data, we investigated the association between previous childbirths and WM brain age in 8,895 women in the UK Biobank cohort (age range = 54 - 81 years). The results showed that number of previous childbirths was negatively associated with WM brain age, potentially indicating a protective effect of parity on brain WM later in life. Both global WM and grey matter brain age estimates showed unique contributions to the association with previous childbirths, suggesting partly independent processes. Corpus callosum contributed uniquely to the global WM association with previous childbirths, and showed a stronger relationship relative to several other tracts. While our findings demonstrate a link between reproductive history and brain WM characteristics later in life, longitudinal studies are required to establish causality and determine how parity may influence women’s WM trajectories across the lifespan.
Determination of the fixed oil quality of ripepistacia lentiscusfruits andOpuntia-ficus indicaseeds
Authors: Kechidi Mohamed , Chalal Mohamed Anis , Bouzenad Amel , Gherib Asma , Touahri Brahim , Mustapha Mohamed Abou , Ourihene Mohamed
Published: November 2020

Pistacia lentiscusandOpuntia-ficus indicaare used in several fields, this study made it possible to highlight the determination of the oil quality from the fruits ofPistacia lentiscusand that of the seeds oil ofOpuntia-ficus indica, and this, by determining its physicochemical parameters such as acid value, saponification and insaponification value, iodine index, peroxyd value, as well as refraction index, humidity and their biochemical compositions, in particular the fatty acids (by CPG) from the samples of oils collected from the region of Khemis Miliana (Ain defla) and extracted by a mechanical method. The results show a quantitative difference between the oily samples in percentage of fatty acids. The contents of Oleic Acid, Linoleic Acid and Palmitic Acid are highest in the case of lentisk oil and are respectively 58.35%, 19.65%, 19.63%. However, the content of Linoleic Acid, Oleic Acid, Palmitic Acid and Stearic Acid are highest in the case of prickly pear and are respectively 63.74%, 21.30%, 10.17%, 3.58%.
Correcting for Superficial Bias in 7T Gradient Echo fMRI
Authors: Huang Pei , Correia Marta M. , Rua Catarina , Rodgers Christopher T. , Henson Richard N. , Carlin Johan D.
Published: November 2020

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The arrival of submillimetre ultra high-field fMRI makes it possible to compare activation profiles across cortical layers. However, the Blood Oxygenation Level Dependent (BOLD) signal measured by Gradient-Echo fMRI is biased towards superficial layers of the cortex, which is a serious confound for laminar analysis. Several univariate and multivariate analysis methods have been proposed to correct this bias. We compare these methods using computational simulations and example human 7T fMRI data from Regions-of-Interest (ROIs) during a visual attention paradigm. The simulations show that two methods - the ratio of ROI means across conditions and a novel application of Deming regression - offer the most robust correction for superficial bias. Deming regression has the additional advantage that it does not require that the conditions differ in their mean activation over voxels within an ROI. When applied to the example dataset, these methods suggest that attentional modulation of activation is similar across cortical layers within the ventral visual stream, despite a naïve activation-based analysis producing stronger modulation in superficial layers. Our study demonstrates that accurate correction of superficial bias is crucial to avoid drawing erroneous conclusions from laminar analyses of Gradient-Echo fMRI data.
Lysine methylation shields an intracellular pathogen from ubiquitylation
Authors: Engström Patrik , Burke Thomas P. , Iavarone Anthony T. , Welch Matthew D.
Published: November 2020

Many intracellular pathogens avoid detection by their host cells. However, it remains unknown how they avoid being tagged by ubiquitin, an initial step leading to anti-microbial autophagy. Here, we show that the intracellular bacterial pathogenRickettsia parkeriuses two protein-lysine methyltransferases (PKMTs) to modify outer membrane proteins (OMPs) and prevent their ubiquitylation. Mutants deficient in the PKMTs were avirulent in mice and failed to grow in macrophages due to ubiquitylation and autophagy. Analysis of the lysine-methylome revealed that PKMTs modify a subset of OMPs by methylation at the same sites that are recognized by host ubiquitin. These findings show that lysine methylation is an essential determinant of rickettsial pathogenesis that shields bacterial proteins from ubiquitylation to evade autophagic targeting.
VirB, a key transcriptional regulator of virulence plasmid genes inShigella flexneri, forms DNA-binding site dependent foci in the bacterial cytoplasm
Authors: Socea Jillian N. , Bowman Grant R. , Wing Helen J.
Published: November 2020

VirB is a key regulator of virulence genes located on the large virulence plasmid (pINV) of the bacterial pathogenShigella flexneri.VirB is unusual in that it is not related to other transcriptional regulators, instead, it belongs to a protein family that primarily functions in plasmid and chromosome partitioning; exemplified by ParB. Despite this, VirB does not function to segregate DNA, but rather counters transcriptional silencing of virulence genes mediated by the nucleoid structuring protein, H-NS. Since ParB localizes subcellularly as discrete foci in the bacterial cytoplasm, we chose to investigate the subcellular localization of VirB to gain novel insight into how VirB functions as a transcriptional anti-silencer. To do this, a GFP-VirB fusion that retains the regulatory activity of VirB and yet, does not undergo significant protein degradation in S.flexneri,was used. Surprisingly, discrete fluorescent foci were observed in live wild-type S.flexnericells and an isogenicvirBmutant using fluorescence microscopy. In contrast, foci were rarely observed (<10%) in cells cured of pINV. Moreover, in the context of the fusion, amino acid substitutions in the DNA binding domain of VirB resulted in the fluorescent signal becoming entirely diffuse. Combined, these data demonstrate that the VirB:DNA interactions required for the transcriptional anti-silencing activity of VirB on pINV are a prerequisite for the subcellular localization of VirB in the bacterial cytoplasm. The significance of these findings, in light of the anti-silencing activity of VirB, is discussed.

Importance

This study reveals the subcellular localization of VirB, a key transcriptional regulator of virulence genes found on the large virulence plasmid inShigella.Fluorescent signals generated by an active GFP-VirB fusion form 2, 3, or 4 discrete foci in the bacterial cytoplasm, predominantly at the quarter cell position. These signals are completely dependent upon VirB interacting with its DNA binding site found either on the virulence plasmid or an engineered surrogate. Our findings: 1) provide novel insight into VirB:pINV interactions, 2) suggest that VirB may have utility as a DNA marker, and 3) raise questions about how and why this anti-silencing protein that controls virulence gene expression on pINV ofShigellaspp. forms discrete foci/hubs within the bacterial cytoplasm.
Harmonization of whole genome sequencing for outbreak surveillance of Enterobacteriaceae and Enterococci
Authors: Jamin Casper , de Koster Sien , van Koeveringe Stefanie , de Coninck Dieter , Mensaert Klaas , de Bruyne Katrien , Selva Natascha Perales , Lammens Christine , Goossens Herman , Hoebe Christian , Savelkoul Paul , van Alphen Lieke ,   and the i-4-1-Health Study Group
Published: November 2020

Whole genome sequencing (WGS), is becoming the facto standard for bacterial typing and outbreak surveillance of resistant bacterial pathogens. We performed a three-center ring trial to assert if inter-laboratory harmonization of WGS is achievable, for this goal. To this end, a set of 30 bacterial isolates comprising of various species belonging to the Enterobacteriaceae and Enterococcus genera were selected and sequenced using the same protocol on the Illumina MiSeq platform in each individual centre. All generated sequencing data was analysed by 1 centre using BioNumerics (6.7.3) for i) genotyping origin of replications & antimicrobial resistance genes, ii) core-genome (cgMLST) forE. coliandK. pneumoniae& whole-genome multi locus sequencing typing (wgMLST) for all species. Additionally, a split k-mer analysis was performed to determine the number of SNPs between samples. A precision of 99.0% and an accuracy of 99.2% was achieved for genotyping. Based on cgMLST, only in 2/27 and 3/15 comparisons a discrepant allele was called between two genomes, forE. coliandK. pneumonia,respectively. Based on wgMLST, the number of discrepant alleles ranged from 0 to 7 (average 1.6). For SNPs, this ranged from 0-11 SNPs (average 3.4). Furthermore, we demonstrate that using differentde novoassemblers to analyse the same dataset introduces up to 150 SNPs, which surpasses most thresholds for bacterial outbreaks. This shows the importance of harmonisation of data processing surveillance of bacterial outbreaks. Summarizing, multi-center WGS for bacterial surveillance is achievable, but only if protocols are harmonized.
Automatic Analysis of Bees’ Waggle Dance
Authors: Reece Jordan , Couvillon Margaret , Grüter Christoph , Ratnieks Francis , Reyes-Aldasoro Constantino Carlos
Published: November 2020

This work describe an algorithm for the automatic analysis of the waggle dance of honeybees. The algorithm analyses a video of a beehive with 13,624 frames, acquired at 25 frames/second. The algorithm employs the following traditional image processing steps:conversion to grayscale, low pass filtering, background subtraction, thresholding, tracking and clusteringto detect run of bees that perform waggle dances. The algorithm detected 44,530 waggle events, i.e. one bee waggling in one time frame, which were then clustered into 511waggle runs. Most of these were concentrated in one section of the hive. The accuracy of the tracking was 90% and a series of metrics like intra-dance variation in angle and duration were found to be consistent with literature. Whilst this algorithm was tested on a single video, the ideas and steps, which are simple as compared with Machine and Deep Learning techniques, should be attractive for researchers in this field who are not specialists in more complex techniques.
N6-methyladenosine (m6A) is an endogenous A3 adenosine receptor ligand
Authors: Ogawa Akiko , Nagiri Chisae , Shihoya Wataru , Inoue Asuka , Kawakami Kouki , Hiratsuka Suzune , Aoki Junken , Ito Yasuhiro , Suzuki Takeo , Suzuki Tsutomu , Inoue Toshihiro , Nureki Osamu , Tanihara Hidenobu , Tomizawa Kazuhito , Wei Fan-Yan
Published: November 2020

About 150 post-transcriptional RNA modifications have been identified in all kingdoms of life. During RNA catabolism, most modified nucleosides are resistant to degradation and are released into the extracellular space. In this study, we explored the physiological role of these extracellular modified nucleosides and found thatN6-methyladenosine (m6A), widely known as an epigenetic mark in RNA, acts as a ligand for the adenosine A3 receptor, for which it has greater affinity than unmodified adenosine. Structural modeling defined the amino acids required for specific binding of m6A to the A3 receptor. m6A is dynamically released in response to cytotoxic stimuli and facilitates type I allergy. Our findings shed light on m6A as a signaling molecule with the ability to activate GPCRs, a previously unreported property of RNA modifications.
Public LC-Orbitrap-MS/MS Spectral Library for Metabolite Identification
Authors: Phapale Prasad , Palmer Andrew , Gathungu Rose Muthoni , Kale Dipali , Brügger Britta , Alexandrov Theodore
Published: November 2020

Liquid chromatography-mass spectrometry(LC-MS)-based untargeted metabolomics studies require high-quality spectral libraries for reliable metabolite identification. We have constructed EMBL-MCF, an open LC-MS/MS spectral library that currently contains over 1600 fragmentation spectra from 435 authentic standards of endogenous metabolites and lipids. The unique features of the library are presence of chromatographic profiles acquired with different LC-MS methods and coverage of different adduct ions. The library covers many biologically important metabolites with some unique metabolites and lipids as compared to other public libraries. The EMBL-MCF spectral library is created and shared using anin-housedeveloped web-application athttps://curatr.mcf.embl.de/. The library is freely available online and also integrated with other mass spectral repositories.
Lipidomic analysis of roseobacters of the pelagic RCA cluster and their response to phosphorus limitation
Authors: Silvano Eleonora , Yang Mingyu , Wolterink Mathias , Giebel Helge-Ansgar , Simon Meinhard , Scanlan David J , Zhao Yanlin , Chen Yin
Published: November 2020

The marine roseobacter-clade Affiliated cluster (RCA) represents one of the most abundant groups of bacterioplankton in the global oceans, particularly in temperate and sub-polar regions. They play a key role in the biogeochemical cycling of various elements and are important players in oceanic climate-active trace gas metabolism. In contrast to copiotrophic roseobacter counterparts such asRuegeria pomeroyiDSS-3 andPhaeobactersp. MED193, RCA bacteria are truly pelagic and have smaller genomes. We have previously shown that RCA bacteria do not appear to encode the PlcP-mediated lipid remodelling pathway, whereby marine heterotrophic bacteria remodel their membrane lipid composition in response to phosphorus (P) stress by substituting membrane glycerophospholipids with alternative glycolipids or betaine lipids. In this study, we report lipidomic analysis of six RCA isolates. In addition to the commonly found glycerophospholipids such as phosphatidylglycerol and phosphatidylethanolamine, RCA bacteria synthesise a relatively uncommon phospholipid, acylphosphatidylglycerol, which is not found in copiotrophic roseobacters. Instead, like the abundant SAR11 clade, RCA bacteria upregulate ornithine lipid biosynthesis in response to P stress, suggesting a key role of this aminolipid in the adaptation of marine heterotrophs to oceanic nutrient limitation.