bluuebunny/crossref_metadata_2025 huggingface dataset:
A High-Quality Genome Assembly for Cercospora janseana, Causal Agent of Narrow Brown Leaf Spot of Rice
Authors: Searight Jacob , Famoso Adam N. , Zhou Xin-Gen , Doyle Vinson P. , Richards Jonathan K.
Published: May 2023

Cercospora janseana causes narrow brown leaf spot of rice. A nearly complete telomere-to-telomere reference genome was assembled with a combination of Oxford Nanopore and Illumina sequences. The genome assembly has a total length of 39,075,509 bp and consists of 15 chromosomes, 14 of which have telomeric repeats at both ends. The assembly N50 is 2.97 Mb and the L50 is five contigs. RNA-seq-mediated gene annotation identified 10,850 genes, including 955 predicted secreted proteins and 361 predicted effector proteins. This highly contiguous and almost complete C. janseana reference genome will be a vital resource for further investigation of host-pathogen interactions and genome evolution within this pathosystem.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Lathyrus sativus Resistance Against the Existing and Emerging Pathogens Erysiphe pisi and E. trifolii: A Case of Commonalities or Total Discrepancy?
Authors: Martins Davide , Santos Carmen , Sampaio Ana Margarida , Rubiales Diego , Patto Maria Carlota Vaz
Published: May 2023

Powdery mildew on Lathyrus sativus (grass pea) is commonly caused by Erysiphe pisi, the causal agent of pea powdery mildew. E. trifolii could also pose an additional threat to grass pea, as it does to pea ( Pisum sativum). In order to understand the potential threat and the availability of resistance sources, the response to both pathogens was analyzed on a worldwide germplasm collection of 189 grass pea accessions. Infection type and disease severity (DS) of grass pea accessions, independently inoculated with E. pisi and E. trifolii, were evaluated under controlled conditions. A wide range of responses were detected, with the previously uncharacterized partial resistance to E. trifolii in grass pea detected less frequently and uncorrelated with partial resistance against E. pisi. To test for the lack of correlation at the genetic level, an exploratory association mapping study was undertaken by statistically combining grass pea collection DS scores against both pathogens, with 5,651 previously screened genotype-by-sequencing-based single nucleotide polymorphisms (SNP). Mostly different genetic regions in grass pea were identified as being associated with the response to E. trifolii and E. pisi, anticipating an independent genetic basis that requires further validation in larger germplasm collections, with higher SNP densities. This study proposes common and unique partial resistance components against two different powdery mildews, implying the need for complementary approaches to introduce resistance to both pathogens into new grass pea varieties. The identified sources of resistance and predicted genomic targets will assist in breeding for resistance to multiple powdery mildews.
The triggering receptor expressed on myeloid cells 2–apolipoprotein E signaling pathway in diseases
Authors: Lyu Shukai , Lan Zhuoqing , Li Caixia
Published: May 2023

Triggering receptor expressed on myeloid cells 2 (TREM2) is a membrane receptor on myeloid cells and plays an important role in the body's immune defense. Recently, TREM2 has received extensive attention from researchers, and its activity has been found in Alzheimer's disease, neuroinflammation, and traumatic brain injury. The appearance of TREM2 is usually accompanied by changes in apolipoprotein E (ApoE), and there has been a lot of research into their structure, as well as the interaction mode and signal pathways involved in them. As two molecules with broad and important roles in the human body, understanding their correlation may provide therapeutic targets for certain diseases. In this article, we reviewed several diseases in which TREM2 and ApoE are synergistically involved in the development. We further discussed the positive or negative effects of the TREM2–ApoE pathway on nervous system immunity and inflammation.
Primary Cutaneous Marginal Zone Lymphoproliferative Disorder of Donor Origin after Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Bejarano Lía , Sayagués Jose María , Alcoceba Miguel , Balanzategui Ana , Lopez-Corral Lucia , Cañueto Javier , Santos-Briz Angel
Published: May 2023

Primary cutaneous posttransplant lymphoproliferative disorders (PTLDs) after allogeneic hematopoietic stem cell transplant (allo-HSCT) are exceedingly rare, with only 6 published cases, all of them consisting in T-cell neoplasms. In this report, we present for the first time a donor-derived B-cell PTLD consisting in a primary, cutaneous, B-cell, marginal zone, lymphoproliferative disorder (PCMZLPD). The patient, a 37-year-old woman with a history of Hodgkin lymphoma received an allo-HSCT from her healthy, matched, related father, achieving complete host chimerism in the bone marrow and peripheral blood. However, 8 years after the allo-HSCT, she presented asymptomatic skin lesions consisting in oval, well-defined, slightly raised erythematous plaques, located on the arms, trunk, and legs. Skin biopsies of 2 lesions demonstrated a class-switched IgG+, EBV-, PCMZLPD, showing kappa light chain restriction and monoclonal rearrangement of the IgH gene. Microsatellite genotyping and 2-color fluorescence in situ hybridization (X and Y chromosomes) confirmed that the origin of the neoplastic cells was the donor graft. The lesions showed an indolent behavior, good response to topical corticosteroids, and no need for systemic treatment. Our case broadens the spectrum of PTLD, a diverse group of lymphoid and/or plasmacytic proliferations with variable clinical presentations and histopathological features.
Postpartum Hemorrhage—Epidemiology, Risk Factors, and Causes
Authors: Patek Kara , Friedman Perry
Published: May 2023

The incidence of postpartum hemorrhage (PPH) is increasing worldwide and in the United States. Coinciding, is the increased rate of severe maternal morbidity with blood transfusion in the United States over the past 2 decades. Consequences of PPH can be life-threatening and carry significant cost burden to the health care system. This review will discuss the current trends, distribution, and risk factors for PPH. Causes of PPH will be explored in detail.
Maternal Coagulation Disorders and Postpartum Hemorrhage
Authors: Bank Tracy C. , Ma’ayeh Marwan , Rood Kara M.
Published: May 2023

Coagulation disorders are rare causes of postpartum hemorrhage. Disturbances in coagulation should be suspected in patients with a family history of coagulopathy, those with a personal history of heavy menstrual bleeding, and those with persistent bleeding despite correction of other causes. The coagulopathic conditions discussed include disseminated intravascular coagulation, platelet disorders, and disturbances of coagulation factors. These should not be overlooked in the evaluation of obstetric hemorrhage, as diagnosis and appropriate treatment may prevent severe maternal morbidity and mortality.
Effect of radiofrequency ablation in addition to biliary stent on overall survival and stent patency in malignant biliary obstruction: an updated systematic review and meta-analysis
Authors: Tarar Zahid Ijaz , Farooq Umer , Gandhi Mustafa , Ghous Ghulam , Saleem Saad , Kamal Faisal , Imam Zaid , Jamil Laith
Published: May 2023

Objectives

Radiofrequency ablation (RFA) is used in addition to stent placement to manage extrahepatic malignant biliary obstruction. We aimed to study the effect of RFA on overall survival (OS) and stent patency in malignant biliary obstruction.

Methods

A comprehensive literature search was performed from inception to May 2022 for all studies measuring the effect of RFA plus stents compared to stents placement only on OS and stent patency in patients with malignant biliary obstruction. We measured differences in OS, stent patency, and odds of adverse events. A random effect model was used to pool data for stent patency, OS, and adverse event.

Results

A total of 17 studies (14 observational and 3 RCT) containing 1766 patients were included in the analysis. The weighted pooled mean survival difference was 58.5 days [95% confidence interval (CI): 32.6–84.4, I
2 = 71%] in favor of the RFA treatment group. The weighted mean difference in stent patency was better in the RFA plus stent group by 45.3 days (95% CI: 30.1–60.5, I
2 = 16.4%) compared to stent only group. The pooled odds of adverse events were the same in both groups [odds ratio (OR) 1.52, 95% CI: 0.96–2.43, I
2 = 59%], and no serious adverse event was seen in either group, or no death reported secondary to RFA procedure. No difference in stent patency based on procedure type, including percutaneous transhepatic cholangiography versus endoscopic retrograde cholangiopancreatography (P = 0.06), and an underline cause of bile duct obstruction was found (P = 0.261).

Conclusion

RFA treatment, in addition to stent placement in malignant biliary obstruction, potentially improves OS and stent patency duration.
Insights Regarding Optometric Findings of CHARGE Syndrome in a Pediatric Low Vision Clinic
Authors: Donahue Alicia M. , Deffler Rebecca A. , Kran Barry S. , Ross Nicole C.
Published: May 2023

Significance

CHARGE, named for common findings: coloboma, heart defects, atresia of choanae, retardation of growth and development, genital hypoplasia and ear anomalies, is a frequent etiology of deaf-blindness. A retrospective review in a pediatric low vision clinic presented the opportunity to investigate ocular findings in this syndrome with variable clinical presentations.

Purpose

This retrospective study reviewed ocular findings and visual function measures from low vision evaluations of patients with CHARGE syndrome, which may influence their multidisciplinary management.

Methods

A retrospective chart review was conducted by three examiners of 60 patients presenting with CHARGE syndrome at a pediatric low vision clinic. Visual acuity and contrast sensitivity were obtained using standard measures. Ocular alignment and cycloplegic refractive error measurements were recorded. Refractive findings were analyzed using vector analysis. Anterior and posterior segment findings were recorded.

Results

Patients ranged in age from 1 to 29 years and were followed for a mean of 4.3 years. Best-corrected visual acuity ranged from no light perception to 20/20 Snellen equivalent. Characteristics of strabismus, occurring in 82% of patients, were reported. Contrast sensitivity was reduced in 52% of patients. Chorioretinal coloboma were reported in 88% of patients. The most common ocular findings included nystagmus (43%), microphthalmia (27%), iris coloboma (27%), and facial nerve palsy (23%). Refractive vector analysis revealed significant myopic progression of the spherical equivalent with age and a tendency for with the rule astigmatism and minimal obliquity.

Conclusions

This retrospective review of a relatively large sample size for this rare condition, outlined the most common ocular manifestations of CHARGE syndrome. Decreased visual acuity, myopic refractive error, strabismus, and reduced contrast sensitivity were common. Thus, careful optometric evaluation in this population is required, as these findings must be considered in appropriate clinical and habilitative management.
Rapid and accurate detection of Shiga toxin-producing Escherichia coli (STEC) serotype O157 : H7 by mass spectrometry directly from the isolate, using 10 potential biomarker peaks and machine learning predictive models
Authors: Manfredi Eduardo , Rocca María Florencia , Zintgraff Jonathan , Irazu Lucía , Miliwebsky Elizabeth , Carbonari Carolina , Deza Natalia , Prieto Monica , Chinen Isabel
Published: May 2023

Introduction. The different pathotypes of

Escherichia coli

can produce a large number of human diseases. Surveillance is complex since their differentiation is not easy. In particular, the detection of Shiga toxin-producing

Escherichia coli

(STEC) serotype O157 : H7 consists of stool culture of a diarrhoeal sample on enriched and/or selective media and identification of presumptive colonies and confirmation, which require a certain level of training and are time-consuming and expensive.

Hypothesis. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a quick and easy way to obtain the protein spectrum of a microorganism, identify the genus and species, and detect potential biomarker peaks of certain characteristics.

Aim. To verify the usefulness of MALDI-TOF MS to rapidly identify and differentiate STEC O157 : H7 from other

E. coli

pathotypes.

Methodology. The direct method was employed, and the information obtained using Microflex LT platform-based analysis from 60 clinical isolates (training set) was used to detect differences between the peptide fingerprints of STEC O157 : H7 and other

E. coli

strains. The protein profiles detected laid the foundations for the development and evaluation of machine learning predictive models in this study.

Results. The detection of potential biomarkers in combination with machine learning predictive models in a new set of 142 samples, called ‘test set‘, achieved 99.3 % (141/142) correct classification, allowing us to distinguish between the isolates of STEC O157 : H7 and the other

E. coli

group. Great similarity was also observed with respect to this last group and the

Shigella

species when applying the potential biomarkers algorithm, allowing differentiation from STEC O157 : H7

Conclusion. Given that STEC O157 : H7 is the main causal agent of haemolytic uremic syndrome, and based on the performance values obtained in the present study (sensitivity=98.5 % and specificity=100.0 %), the implementation of this technique provides a proof of principle for MALDI-TOF MS and machine learning to identify biomarkers to rapidly screen or confirm STEC O157 : H7 versus other diarrhoeagenic

E. coli

in the future.
Quantifying the Risk of General Health and Early COVID-19 Spread in Residential Buildings with Deep Learning and Expert-augmented Machine Learning
Authors: Guan Jingjing , Leung Eman , Kwok Kin On , Hung Chi Tim , Lee Albert , Chong Ka Chun , Yam Carrie Ho Kwan , Cheung Clement KM. , Tieben Hendrik , Tsang Hector W.H. , Yeoh Eng-kiong
Published: May 2023

Buildings’ built environment has been linked to their occupants’ health. It remains unclear whether those elements that predisposed its residents to poor general health before the two SARS pandemics also put residents at risk of contracting COVID-19 during early outbreaks. Relevant research to uncover the associations is essential, but there lacks a systematic examination of the relative contributions of different elements in one’s built environment and other non-environmental factors, singly or jointly. Hence, the current study developed a deep-learning approach with multiple input channels to capture the hierarchical relationships among an individual’s socioecology’s demographical, medical, behavioral, psychosocial, and built-environment levels. Our findings supported that 1) deep-learning models whose inputs were structured according to the hierarchy of one’s socioecology outperformed plain models with one-layered input in predicting one’s general health outcomes, with the model whose hierarchically structured input layers included one’s built environment performed best; 2) built-environment features were more important to general health compared to features of one’s sociodemographic and their health-related quality of life, behaviors, and service utilization; 3) a composite score representing built-environment features’ statistical importance to general health significantly predicted building-level COVID-19 case counts; and 4) building configurations derived from the expert-augmented learning of granular built-environment features that were of high importance to the general health were also linked to building-level COVID-19 case counts of external samples. Specific built environments put residents at risk for poor general health and COVID-19 infections. Our machine-learning approach can benefit future quantitative research on sick buildings, health surveillance, and housing design.

Highlights

The current modeling approaches for COVID-19 transmission at early spread are limited due to uncertainty and rare events.

Socio-ecological structure (SES) can organize variables from different hierarchies of a total environment.

TensorFlow-based deep learning with recurrent and convolutional neural networks is developed to explain general health with SES-organized variables.

Among SES factors, built environments have a greater association with general health.

Built-environment risks on individual general health associated with early-spread COVID-19 infections in residential buildings.
ANAEMIA IN CHILDREN AGED 7 MONTHS TO 12 YEARS AND ASSOCIATED FACTORS: A CROSS-SECTIONAL STUDY OF CHILDREN ADMITTED AT THE EFFIDUASE DISTRICT HOSPITAL AND AHMADIYYA MISSION HOSPITAL, GHANA
Authors: Barimah Antwi Joseph , Ibrahim Mohammed Mohammed , Allotey Solomon Saka , Amoah Bernard Opoku , Agyemang Larry , Dumba James , Nketiah Yaw Boakye , Commey Rebecca Dorcas , Alorvi Semefa , Ampofo Deborah
Published: May 2023

A number of factors have been identified as influencing the prevalence of anaemia in children. In the Sekyere East district, an increasing trend of children with severe anaemia leading to haemotransfusion has been observed. Over a three-month period (June to August 2022) approximately one hundred (100) children were haemotransfused due to severe anaemia in the Effiduase district hospital. This quantitative oriented study adopted the descriptive cross-sectional study design. Specifically, the study sought to explore the prevalence of childhood anaemia and its associated factors in the district. Purposive sampling technique which is a non-probability (non-randomized) was used to select children and their guardians to partake in the study. SPSS statistical software version 25 was used to analyze quantitative data of this study and data were presented in frequencies using tables. This study has accentuated high prevalence of anaemia in the Sekyere East district looking at the various findings brought to light by the Haemoglobin (Hb) blood analysis, Mean Corpuscular Volume (MCV) blood tests and the Mean Corpuscular Haemoglobin (MCH) test results. The findings from the study have also shown that malaria in children is significantly associated with the onset of childhood anaemia. The study additionally revealed moderate nutritional intake of food products very rich in iron, vitamin B12 and folate nutrients necessary to curb anaemia in children. In conclusion, study findings therefore underscore the need for multi-faceted approaches that address both malaria control and nutrition in order to reduce anaemia among the children in the Sekyere East district.
Evaluating the Performance of the DPP® ZDC IgM/IgG Rapid Test for Chikungunya Virus Diagnosis in Febrile Outpatients: A Prospective, Diagnostic Accuracy Study
Authors: Moreira José , Barros Janaina , Fernandez-Carballo B. Leticia , Escadafal Camille , Ribeiro Guilherme S. , Dittrich Sabine , Brasil Patrícia , Siqueira André M.
Published: May 2023

Objective

Evaluate the performance of a novel antibody-based rapid diagnostic test (RDT) for detecting Chikungunya virus (CHIKV) infection in febrile patients in Rio de Janeiro, Brazil.

Methods

We prospectively enrolled non-severe febrile patients aged 2-65 years presenting as outpatients between October 2018 and July 2019. Serum samples were collected during acute and convalescent phases and tested for CHIKV antibodies using the DPP® ZDC IgM/IgG rapid test and compared against the reference test, CHIKV RT-PCR. We determined the seropositivity using ELISA IgM/IgG and evaluated the diagnostic performance of the WHO-endorsed CHIKV clinical definition against the reference test.

Results

Of 500 participants, 226/261 (86.5%) tested ELISA IgM positive, 45/271 (16.6%) tested ELISA IgG positive, 100/294 (34%) CHIKV RT-PCR positive, and 117/495 (23.6%) RDT-antibody positive. During the acute phase [median 3 (2-4) days post illness onset], the sensitivity of IgM, IgG, and combined IgM/IgG ranged from 14.71-34.85%, while specificity ranged from 63.32-65.61%. During the convalescent phase [mean 16.5 (±5.5) days post-illness onset], sensitivity increased from 65.75% to 77.78%, and specificity ranged from 93.33-98.11%. The WHO’s CHIKV clinical definition had a sensitivity, specificity, positive predictive value, and negative predictive value of 88 (79.9-93.6)%, 74 (68-80)%, 64.2 (58.2-69.8)%, and 92.3 (87.6-95.3)%, respectively.

Conclusions

The DPP® ZDC IgM/IgG accurately diagnosed CHIKV on samples collected during the convalescent phase. Field applications include investigating CHIKV in patients with sub-acute to chronic osteoarticular symptoms and conducting serosurveys to inform priority areas for CHIKV vaccine implementation. The WHO’s clinical definition of CHIKV was accurate and could be deployed, especially in regions with limited diagnostic capacity.

Clinicaltrials.gov

NCT03047642
The 100 most-cited articles in soccer injuries: a bibliometric study
Authors: Chaabeni Amr , Kalai Amine , Slama Meryam , Ben Salah Frih Zohra , Jellad Anis
Published: May 2023

Bibliometric analysis is an increasingly popular method for assessing aspects of a specific field of research and identifying its emerging areas of interest. Although it has been increasingly used in sports medicine research to assess injuries, few studies have focused on soccer. The purpose of our study was to identify the 100 most-cited publications related to soccer injuries and conduct a thorough bibliometric mapping analysis to understand the research trends. Using the Clarivate Analytics Web of Science Database and Bibliometrix R-package software, we identified 100 articles with 26,046 total citations (range = 146-945) published between 1990 and 2017. Most were published in theBritish Journal of Sports Medicine(32 articles) andAmerican Journal of Sports Medicine(31 articles), and most corresponding authors originated from Sweden. About half of the articles were descriptive or epidemiology studies using level-2 evidence. The main research topics were epidemiology (25 articles) and prevention (24 articles). Most focused on male and adult elite soccer players.
Troponin Level at Presentation as a Prognostic Factor Among Patients Presenting with non-ST Segment Elevation Myocardial Infarction
Authors:   the Jerusalem platelets thrombosis and intervention in cardiology (JUPITER-18) study group, Loutati Ranel , Perel Nimrod , Bruoha Sharon , Taha Louay , Tabi Meir , Marmor David , Amsalem Itshak , Hitter Rafael , Manassra Mohammed , Hamayel Kamal , Karameh Hani , Maller Tommer , Steinmetz Yoed , Karmi Mohammad , Shuvy Mony , Glikson Michael , Asher Elad
Published: May 2023

Introduction

Timely reperfusion within 120 minutes is strongly recommended in patients presenting with non-ST segment myocardial infarction (NSTEMI) with very high-risk features. Evidence regarding the use of high sensitivity cardiac troponin (hs-cTn) concentration upon admission for the risk-stratification of patients presenting with NSTEMI in order to expedite percutaneous coronary intervention (PCI) and thus potentially improve outcomes is limited.

Methods

All patients admitted to a tertiary care center intensive cardiac care unit (ICCU) between July 2019 – July 2022 were included and were followed for up to 3 years. Hs-cTnI level on presentation was recorded and patients were divided into four quartiles according to their hs-cTnI level on admission. Association between the initial hs-cTnI level and all-cause mortality during the follow-up period was examined.

Results

A total of 544 NSTEMI patients with a median age of 67 were included. There was no difference between the initial hs-cTnI level groups regarding age and comorbidities. A higher mortality rate was observed in the highest hs-cTnI quartile as compared with the lowest hs-cTnI quartile (16.2% vs. 7.35%, p=0.03) with Hazard ratio (HR) for mortality of 2.6 (CI: 1.23-5.4; p=0.012).

Conclusions

Patients presenting with NSTEMI and higher Hs-cTnI levels on admission were at higher risk for mortality during follow-up. This finding supports further prospective studies to examine the impact of early reperfusion strategy on mortality in patients presenting with NSTEMI according to degree of troponin elevation on admission.
WEGS: a cost-effective sequencing method for genetic studies combining high-depth whole exome and low-depth whole genome
Authors: Bhérer Claude , Eveleigh Robert , Trajanoska Katerina , St-Cyr Janick , Paccard Antoine , Ravindran Praveen Nadukkalam , Caron Elizabeth , Asbah Nimara Bader , Wei Clare , Baumgartner Iris , Schindewolf Marc , Döring Yvonne , Perley Danielle , Lefebvre François , Lepage Pierre , Bourgey Mathieu , Bourque Guillaume , Ragoussis Jiannis , Mooser Vincent , Taliun Daniel
Published: May 2023

0

Whole genome sequencing (WGS) at high-depth (30X) allows the accurate discovery of variants in the coding and non-coding DNA regions and helps elucidate the genetic underpinnings of human health and diseases. Yet, due to the prohibitive cost of high-depth WGS, most large-scale genetic association studies use genotyping arrays or high-depth whole exome sequencing (WES). Here we propose a novel, cost-effective method, which we call “Whole Exome Genome Sequencing” (WEGS), that combines low-depth WGS and high-depth WES with up to 8 samples pooled and sequenced simultaneously (multiplexed). We experimentally assess the performance of WEGS with four different depth of coverage and sample multiplexing configurations. We show that the optimal WEGS configurations are 1.7-2.0 times cheaper than standard WES (no-plexing), 1.8-2.1 times cheaper than high-depth WGS, reach similar recall and precision rates in detecting coding variants as WES, and capture more population-specific variants in the rest of the genome that are difficult to recover when using genotype imputation methods. We apply WEGS to 862 patients with peripheral artery disease and show that it directly assesses more known disease-associated variants than a typical genotyping array and thousands of non-imputable variants per disease-associated locus.
Study protocol for comparison of post-operative pain between intraosseous multimodal injection and periarticular multimodal injection in Simultaneous Bilateral Total Knee Arthroplasty – A Randomized Controlled Trial
Authors: Ploynumpon Patcharavit , Wilairatana Vajara , Chompoosang Thakrit
Published: May 2023

Abstraction

Background:

Total knee arthroplasty (TKA) was the procedure which is preform by orthopedic surgeons in end stage osteoarthritis knee patients who fail conservative treatment. Periarticular analgesia is one of the effective and safe technique used to reduce pain after surgery. However, the location and formula of the mixture have not yet been controversy. Recently, a study compared intraosseous analgesic injection, which provided significant postoperative pain relief compared to the control group. The authors conducted this study to compare periarticular and intraosseous analgesic injection in patients undergoing simultaneous bilateral total knee arthroplasty.

Method:

The study is a two-arm, double-blinded, randomized controlled trial with 26 patients (52 knees) who underwent simultaneous bilateral total knee arthroplasty. The primary outcome is postoperative pain at 12, 24, and 48 hours using the Visual Analog Scale for assessment. The secondary outcomes include postoperative range of motion at 24 and 48 hours, postoperative blood loss, and postoperative complications.

Discussion:

While periarticular analgesic is the standard practice, intraosseous analgesic injection is a potential route for controlling postoperative pain after total knee arthroplasty surgery. This study offers a better alternative route for analgesic injection.
Tricontinental detection of Streptococcus pyogenes M1UK: A call for wider research and active surveillance
Authors: Vieira Ana , Soo Valerie WC , Li Ho Kwong , Zhi Xiangyun , Reeves Lucy , Huse Kristin K. , Mok Kai Yi , Cowen Oscar , Jauneikaite Elita , Coelho Juliana , Sriskandan Shiranee
Published: May 2023

TheStreptococcus pyogenesM1UKlineage, characterised by an intrinsic ability to express SpeA toxin and defined by 27 single nucleotide polymorphisms in the core genome, dominates the population ofemm1S. pyogenesisolates in England. The lineage has been identified elsewhere in Europe, North America, and, most recently, Australia. SpeA however may not be the sole deterministic factor underlying success of the M1UKlineage. Production of SpeA by strains belonging to an intermediateemm1 sublineage, M123SNP, is indistinguishable from M1UKstrains. Despite this, in England at least, M1UKhas outcompeted strains from the M123SNPsublineage. We infer that the fitness of M1UKresides in additional properties that confer an advantage toS. pyogenes, underlining a need for further research. A single nucleotide polymorphism (SNP) in the ssrA leader sequence upstream ofspeAis one of a limited number of SNPs that distinguish intermediate sublineages that differ in SpeA production. Introduction of the ssrA SNP into representative isolates of the widely disseminated M1globalclone and the intermediate M113SNPlineage (that cannot otherwise produce readily-detectable SpeA in culture) resulted in SpeA expression, confirming the importance of the ssrA SNP to SpeA phenotype. However, RNAseq analysis of clinical strains showed that presence of the SNP was not invariably linked to read-through from the ssrA leader sequence or SpeA expression. Literature review suggests that read through andspeAmRNA transcript length may be impacted by the two component regulator CovRS, pointing to a complex regulatory network interaction between the bacterial chromosome and phage-encoded superantigens.
gcplyr: an R package for microbial growth curve data analysis
Authors: Blazanin Michael
Published: May 2023

Characterization of microbial growth is of both fundamental and applied interest. Modern platforms can automate collection of high-throughput microbial growth curves, necessitating the development of computational tools to handle and analyze these data to produce insights. To address this need, here I present a newly-developed R package: gcplyr. gcplyr can flexibly import growth curve data in common tabular formats, and reshapes it under a tidy framework that is flexible and extendable, enabling users to design custom analyses or plot data with popular visualization packages. gcplyr can also incorporate metadata and generate or import experimental designs to merge with data. Finally, gcplyr carries out model-free (non-parametric) analyses. These analyses do not require mathematical assumptions about microbial growth dynamics, and gcplyr is able to extract a broad range of important traits, including growth rate, doubling time, lag time, maximum density and carrying capacity, diauxie, area under the curve, extinction time, and more. gcplyr makes scripted analyses of growth curve data in R straightforward, streamlines common data wrangling and analysis steps, and easily integrates with common visualization and statistical analyses.

Availability

gcplyr is available from the central CRAN repository (https://CRAN.R-project.org/package=gcplyr), or from GitHub (https://github.com/mikeblazanin/gcplyr).
Particle-based simulations reveal two positive feedback loops allow relocation and stabilization of the polarity site during yeast mating
Authors: Guan Kaiyun , Lew Daniel J. , Elston Timothy C.
Published: May 2023

Many cells adjust the direction of polarized growth or migration in response to external directional cues. The yeastSaccharomyces cerevisiaeorient their cell fronts (also called polarity sites) up pheromone gradients in the course of mating. However, the initial polarity site is often not oriented towards the eventual mating partner, and cells relocate the polarity site in an indecisive manner before developing a stable orientation. During this reorientation phase, the polarity site displays erratic assembly-disassembly behavior and moves around the cell cortex. The mechanisms underlying this dynamic behavior remain poorly understood. Particle-based simulations of the core polarity circuit revealed that molecular-level fluctuations are insufficient to overcome the strong positive feedback required for polarization and generate relocating polarity sites. Surprisingly, inclusion of a second pathway that promotes polarity site orientation generated a mobile polarity site with properties similar to those observed experimentally. This pathway forms a second positive feedback loop involving the recruitment of receptors to the cell membrane and couples polarity establishment to gradient sensing. This second positive feedback loop also allows cells to stabilize their polarity site once the site is aligned with the pheromone gradient.

Author summary

Cells perform many complex tasks, including directed growth, migration, division and differentiation. To accomplish these tasks, the relevant molecular machinery is localized to specific cellular regions. The asymmetric distribution of cellular components is referred to as cell polarity. Polarity is established by localized activation of the protein Cdc42. Establishing mechanisms that regulate the spatiotemporal activity of Cdc42 is a fundamental area of cell biology. Mating yeast cells dynamically relocate a region of high Cdc42 activity, referred to as the polarity site, and grow toward each other after proper alignment of the sites. We investigated mechanisms that generate dynamic polarity sites by performing particle-based simulations of the biochemical reactions that regulate Cdc42 activity. The reactions contain two positive feedback loops that reinforce Cdc42 activity. The first involves autocatalytic activation of Cdc42 through recruitment of an activator. While necessary for polarity establishment, this feedback loop on its own created a stable polarity site that did not relocate. Incorporation of the second feedback loop, which couples the polarity machinery to extracellular mating signals, generated mobile polarity sites. This feedback loop also provides a mechanism for developing stable alignment of polarity sites. Our findings provide insight into how cells regulate polarity dynamics to accomplish complex tasks.
Upregulation of steroidogenesis is associated with coma in human cerebral malaria
Authors: Abdrabou Wael , Gupta Himanshu , Sahu Praveen K. , Mohanty Akshaya K. , Pattnaik Rajyabardhan , Hoffmann Angelika , Mohanty Sanjib , Wassmer Samuel C. , Idaghdour Youssef
Published: May 2023

P. falciparumparasites manipulate host metabolic processes during malaria to ensure their survival and progression, causing the host and parasite metabolic pathways to become intertwined. We analyzed metabolites to evaluate their potential as biomarkers for cerebral malaria (CM). Our analysis of CM (with coma) and CM-like (without coma) patients identified 835 metabolites, including lipids, amino acids, xenobiotics, peptides, nucleotides, carbohydrates, cofactors, and vitamins. Principal component analysis revealed clear segregation between CM-like and CM patients. Metabolite-by-metabolite analysis identified 103 differentially abundant metabolites, 26 of which were significantly lower in CM-like patients (primarily lipids), while 71% of those higher in CM patients were amino acids and xenobiotics. The results revealed significant differences in circulating levels of long chain free fatty acids and catecholamine metabolism and identified steroid biosynthesis as the most enriched lipid metabolism pathway, with eight endogenous steroids showing significantly higher levels in CM patients compared to CM-like patients (FC > 2, B-H FDR-adjusted P < 0.05). These steroids include pregnenolone sulfate, pregnenediol sulfate, pregnenetriol sulfate, androsterone monosulfate, 16α-OH-DHEA-S, DHEA-S, cortisol, and cortisone. High levels of pregnenolone and its downstream metabolic derivatives were significantly associated with coma in CM patients. Our findings suggest that monitoring circulating neurosteroid levels in patients could aid in the early identification of those at risk of coma, and may important implications for the clinical management of CM patients.
Lupus autoantibodies initiate a maladaptive equilibrium sustained by HMGB1:RAGE signaling and reversed by LAIR-1:C1q signaling
Authors: Carroll Kaitlin R. , Mizrachi Mark , Simmons Sean , Toz Bahtiyar , Wingard Jeffrey , Tehrani Nazila , Zarfeshani Aida , Kello Nina , Kowal Czeslawa , Levin Joshua Z. , Volpe Bruce T. , Diamond Betty
Published: May 2023

Cognitive impairment is a frequent manifestation of neuropsychiatric systemic lupus erythematosus (NPSLE), present in up to 80% of patients and leading to a diminished quality of life. We have developed a model of lupus-like cognitive impairment which is initiated when anti-DNA, anti-N-methyl D-aspartate receptor (NMDAR) cross-reactive antibodies, which are present in 30% of SLE patients, penetrate the hippocampus. This leads to immediate, self-limited excitotoxic death of CA1 pyramidal neurons followed by a significant loss of dendritic arborization in the remaining CA1 neurons and impaired spatial memory. Both microglia and C1q are required for dendritic loss. Here we show that this pattern of hippocampal injury creates a maladaptive equilibrium that is sustained for at least one year. It requires HMGB1 secretion by neurons to bind RAGE, a receptor for HMGB1 expressed on microglia, and leads to decreased expression of microglial LAIR-1, an inhibitory receptor for C1q. The angiotensin converting enzyme (ACE) inhibitor captopril, which can restore a healthy equilibrium, microglial quiescence, and intact spatial memory, leads to upregulation of LAIR-1. This paradigm highlights HMGB1:RAGE and C1q:LAIR-1 interactions as pivotal pathways in the microglial–neuronal interplay that defines a physiologic versus a maladaptive equilibrium.
Modelling complex growth profiles ofBacteroides fragilisandEscherichia colion various carbohydrates in an anaerobic environment
Authors: McGuire Zachary , Revuru Sainitya , Zhang Sheng , Blankenberger Amanda , Rasheed Moiz , Hosen Jacob D. , Lin Guang , Verma Mohit S.
Published: May 2023

Previously published models for microbial growth focus only on either death or growth and are unable to account for differently shaped growth curves. Currently, there is no model capable of incorporating combinations of microbial growth trends. This study creates a bacterial growth model that incorporates growth, death, lag, and tail phases as well as applies this model to the growth trends ofBacteroides fragilisandEscherichia colion 13 different carbohydrate substances. Growth trends were collected by measuring the optical densities over 72 hours for eitherB. fragilisorE. coliin a chemically defined media supplemented by a mono- or disaccharide. The Digital Environment to Enable Data-driven Science (DEEDS) platform was utilized to parse data and apply the developed model to obtain parameter values.E. coliwas found to grow on the chemically defined media alone whileB. fragiliswas unable to grow on it alone.E. coligrowth was led by 10 mM concentration of substrates whileB. fragilis growthwas substrate dependent. Bacterial death only occurred forB. fragilisbut was found to be dependent on concentration for the two most significant substrates. A singular model was developed that does not require prior knowledge of metabolomics and is capable of incorporating a combination of growth and death trends.
Structural basis of Gabija anti-phage defense and viral immune evasion
Authors: Antine Sadie P. , Johnson Alex G. , Mooney Sarah E. , Leavitt Azita , Mayer Megan L. , Yirmiya Erez , Amitai Gil , Sorek Rotem , Kranzusch Philip J.
Published: May 2023

Bacteria encode hundreds of diverse defense systems that protect from viral infection and inhibit phage propagation1–5. Gabija is one of the most prevalent anti-phage defense systems, occurring in >15% of all sequenced bacterial and archaeal genomes1,6,7, but the molecular basis of how Gabija defends cells from viral infection remains poorly understood. Here we use X-ray crystallography and cryo-EM to define how Gabija proteins assemble into an ∼500 kDa supramolecular complex that degrades phage DNA. Gabija protein A (GajA) is a DNA endonuclease that tetramerizes to form the core of the anti-phage defense complex. Two sets of Gabija protein B (GajB) dimers dock at opposite sides of the complex and create a 4:4 GajAB assembly that is essential for phage resistancein vivo. We show that a phage-encoded protein Gabija anti-defense 1 (Gad1) directly binds the Gabija GajAB complex and inactivates defense. A cryo-EM structure of the virally inhibited state reveals that Gad1 forms an octameric web that encases the GajAB complex and inhibits DNA recognition and cleavage. Our results reveal the structural basis of assembly of the Gabija anti-phage defense complex and define a unique mechanism of viral immune evasion.
Rapid effects of valproic acid on the fetal brain transcriptome: Implications for brain development and autism
Authors: Dorsey Susan G. , Mocci Evelina , Lane Malcolm V. , Krueger Bruce K.
Published: May 2023

There is an increased incidence of autism among the children of women who take the anti-epileptic, mood stabilizing drug, valproic acid (VPA) during pregnancy; moreover, exposure to VPAin uterocauses autistic-like symptoms in rodents and non-human primates. Analysis of RNA-seq data obtained from E12.5 fetal mouse brains 3 hours after VPA administration revealed that VPA significantly increased or decreased the expression of approximately 7,300 genes. No significant sex differences in VPA-induced gene expression were observed. Expression of genes associated with neurodevelopmental disorders (NDDs) such as autism as well as neurogenesis, axon growth and synaptogenesis, GABAergic, glutaminergic and dopaminergic synaptic transmission, perineuronal nets, and circadian rhythms was dysregulated by VPA. Moreover, expression of 399 autism risk genes was significantly altered by VPA as was expression of 252 genes that have been reported to play fundamental roles in the development of the nervous system but are not otherwise linked to autism. The goal of this study was to identify mouse genes that are:(a) significantly up- or down-regulated by VPA in the fetal brainand(b) known to be associated with autism and/or to play a role in embryonic neurodevelopmental processes, perturbation of which has the potential to alter brain connectivity in the postnatal and adult brain.The set of genes meeting these criteria provides potential targets for future hypothesis-driven approaches to elucidating the proximal underlying causes of defective brain connectivity in NDDs such as autism.
Variance Analysis of LC-MS Experimental Factors and Their Impact on Machine Learning
Authors: Rehfeldt Tobias Greisager , Krawczyk Konrad , Echers Simon Gregersen , Marcatili Paolo , Palczynski Pawel , Röttger Richard , Schwämmle Veit
Published: May 2023

Background

Machine learning (ML) technologies, especially deep learning (DL), have gained increasing attention in predictive mass spectrometry (MS) for enhancing the data processing pipeline from raw data analysis to end-user predictions and re-scoring. ML models need large-scale datasets for training and re-purposing, which can be obtained from a range of public data repositories. However, applying ML to public MS datasets on larger scales is challenging, as they vary widely in terms of data acquisition methods, biological systems, and experimental designs.

Results

We aim to facilitate ML efforts in MS data by conducting a systematic analysis of the potential sources of variance in public MS repositories. We also examine how these factors affect ML performance and perform a comprehensive transfer learning to evaluate the benefits of current best practice methods in the field for transfer learning.

Conclusions

Our findings show significantly higher levels of homogeneity within a project than between projects, which indicates that it’s important to construct datasets most closely resembling future test cases, as transferability is severely limited for unseen datasets. We also found that transfer learning, although it did increase model performance, did not increase model performance compared to a non-pre-trained model.
Discrete cortical control during quiet stance revealed by desynchronization and rebound of beta oscillations
Authors: Nakamura Akihiro , Miura Ryota , Suzuki Yasuyuki , Morasso Pietro , Nomura Taishin
Published: May 2023

Postural sway during quiet stance often exhibits a repetition of micro fall and the subsequent micro recovery. The classical view –that the quiet bipedal stance is stabilized by the ankle joint stiffness– has been challenged by paradoxical non-spring-like behaviors of calf muscles: gastrocnemius muscles are shortened (contract) and then stretched (relax), respectively, during the micro fall and the micro recovery. Here, we examined EEG (electroencephalogram) based brain activity during quiet stance, and identified desynchronization and synchronization of beta oscillations that were associated, respectively, with the micro fall and the micro recovery. Based on a widely accepted scenario for beta-band desynchronization during movement and post-movement rebound in the control of discrete voluntary movement, our results reveal that the beta rebound can be considered as a manifestation of stop command to punctuate the motor control for every fall-recovery cycle. Namely, cortical interventions to the automatic postural control are discrete, rather than continuous modulations. The finding is highly compatible with the intermittent control model, rather than the stiffness control model.
Renal tubular function and morphology revealed in kidney without labeling using three-dimensional dynamic optical coherence tomography
Authors: Mukherjee Pradipta , Fukuda Shinichi , Lukmanto Donny , Tran Thi Hang , Okada Kosuke , Makita Shuichi , El-Sadek Ibrahim Abd , Lim Yiheng , Yasuno Yoshiaki
Published: May 2023

Renal tubule has distinct metabolic features and functional activity that may be altered during kidney disease. In this paper, we present label-free functional activity imaging of renal tubule in normal and obstructed mouse kidney models using three-dimensional (3D) dynamic optical coherence tomography (OCT)ex vivo. To create an obstructed kidney model, we ligated the ureter of the left kidney for either 7 or 14 days. Two different dynamic OCT (DOCT) methods were implemented to access the slow and fast activity of the renal tubules: a logarithmic intensity variance (LIV) method and a complex-correlation-based method. Three-dimensional DOCT data were acquired with a 1.3 μm swept-source OCT system and repeating raster scan protocols. In the normal kidney, the renal tubule appeared as a convoluted pipe-like structure in the DOCT projection image. Such pipe-like structures were not observed in the kidneys subjected to obstruction of the ureter for several days. Instead of any anatomical structures, a superficial high dynamics appearance was observed in the perirenal cortex region of the obstructed kidneys. These findings suggest that volumetric DOCT can be used as a tool to investigate kidney function during kidney diseases.