bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of hepatitis B and hepatitis C in migrants from sub-Saharan Africa at Al Kufra in SE Libya in transit toward Europe
Authors: Saaed Frhat M. A. , Ongerth Jerry E.
Published: February 2022

Background

Viral hepatitis has become a universally established health care challenge due to its worldwide distribution chronic persistence, complications, and high prevalence with unchecked conditions in areas like sub-Saharan Africa. A high proportion of asymptomatic infections allows serious complications in patients who are infected. These asymptomatic infected people pose a serious risk for the transmission of infection to healthy population. This study aimed to detect and examine the prevalence of both HBV and HCV carriers among 3248 newly arrived migrants from different parts of sub-Saharan Africa in Al Kufra, Libya, a remote agricultural North African city. All these migrants were required by the Libyan authorities to undergo a complete medical check-up for different purposes such as joining for new jobs, and for obtaining licenses for trade and commerce.

Methodology

UAT sera from 3,248 migrants, aged 18–53 years, attending the Al Kufra city hospital from January 01 to December 31, 2019, were screened for HBsAg and anti-HCV antibody by rapid tests and positive samples were further tested by ELISA method.

Results

the results showed that 761/3248 (23.4%) of the migrants were positive for HBV and 1014/3248 (31.2%) were positive for HCV.

Conclusion

Migrants newly arrived from sub-Saharan African carry high rates of Hepatitis B and C infections. It is important to increase awareness about occupational health, and the risks of HBV and HCV transmission to the local population. The study results indicate the value of preemployment medical check-up and regular investigation and illustrates the importance of understanding the potential impact on migrant destination populations.
Operationalising the Centiloid Scale for [18F]florbetapir PET Studies on PET/MR
Authors: Coath William , Modat Marc , Cardoso M Jorge , Markiewicz Pawel , Lane Christopher A , Parker Thomas D , Keshavan Ashvini , Buchanan Sarah M , Keuss Sarah E , Harris Matthew J , Burgos Ninon , Dickson John , Barnes Anna , Thomas David L , Beasley Daniel , Malone Ian B , Wong Andrew , Erlandsson Kjell , Thomas Benjamin A , Schöll Michael , Ourselin Sebastien , Richards Marcus , Fox Nick C , Schott Jonathan M , Cash David M ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: February 2022

Purpose

The Centiloid scale provides a systematic means of harmonising amyloid-β PET measures across different acquisition and processing methodologies. This work explores the Centiloid transformation of [18F]florbetapir PET data acquired on a combined PET/MR scanner and processed with methods that differ from the standard Centiloid pipeline.

Methods

The Standard PiB and Florbetapir Calibration datasets were processed using a standardised uptake value ratio (SUVR) pipeline with MRI parcellations from the Geodesic Information Flow (GIF) algorithm in native PET space. We generated SUVRs using whole cerebellum (GIF_WCSUVR) and eroded white matter (GIF_WMSUVR) reference regions, with and without partial volume correction (PVC). Linear regression was used to calibrate these processing pipelines to the standard Centiloid approach. We then applied the resulting transformation to 432 florbetapir scans from the Insight 46 study of mostly cognitively normal individuals aged ∼70 years, and defined Centiloid cutpoints for amyloid-β positivity using Gaussian-mixture modelling.

Results

GIF-based SUVR processing pipelines were suitable for conversion according to Centiloid criteria. For GIF_WCSUVR, cutpoints translated to 14.2 Centiloids, or 11.8 with PVC. There was a differential relationship between florbetapir uptake in WM and WC regions in Florbetapir Calibration and Insight 46 datasets, causing implausibly low Centiloid values for GIF_WMSUVR. Linear adjustment to account for this difference resulted in Centiloid cutpoints of 18.1 for GIF_WMSUVR (17.0 with PVC).

Conclusion

Our results show florbetapir SUVRs acquired on PET/MR scanners can be reliably converted to Centiloids. Acquisition or biological factors can have large effects on Centiloid values from different datasets, we propose a correction to account for these effects.
Assessment of Genetic Susceptibility to Multiple Primary Cancers through Whole-Exome Sequencing in Two Large Multi-Ancestry Studies
Authors: Cavazos Taylor B. , Kachuri Linda , Graff Rebecca E. , Nierenberg Jovia L. , Thai Khanh K. , Alexeeff Stacey , Van Den Eeden Stephen , Corley Douglas A. , Kushi Lawrence H. ,   Regeneron Genetics Center, Hoffmann Thomas J. , Ziv Elad , Habel Laurie , Jorgenson Eric , Sakoda Lori C. , Witte John S.
Published: February 2022

Up to one of every six individuals diagnosed with one cancer will be diagnosed with a second primary cancer in their lifetime. Genetic factors contributing to the development of multiple primary cancers, beyond known cancer syndromes, have been underexplored. To characterize genetic susceptibility to multiple cancers, we conducted a pan-cancer, whole-exome sequencing study of individuals drawn from two large prospective cohorts (6,429 cases, 165,853 controls). We created two groupings of individuals diagnosed with multiple primary cancers: 1) an overall combined set with at least two cancers across any of 36 organ sites; and 2) cancer-specific sets defined by an index cancer at one of 16 organ sites with at least 50 cases from each study population. We then investigated whether variants identified from exome sequencing were associated with these sets of multiple cancer cases in comparison to individuals with one and, separately, no cancers. We identified 22 variant-phenotype associations, 10 of which have not been previously discovered and were significantly overrepresented among individuals with multiple cancers, compared to those with a single cancer. Overall, we describe variants and genes that may play a fundamental role in the development of multiple primary cancers and improve our understanding of shared mechanisms underlying carcinogenesis. Further investigation of these findings may lead to new screening strategies for individuals at risk for multiple primary cancers.
Genetic control of body weight by the human brain proteome
Authors: Gagnon Eloi , Girard Arnaud , Gobeil Émilie , Bourgault Jérôme , Couture Christian , Mitchell Patricia L. , Bouchard Claude , Tremblay Angelo , Mathieu Patrick , Michaud Andréanne , Pérusse Louis , Arsenault Benoit J.
Published: February 2022

Genome-wide association studies (GWAS) have identified hundreds of genetic variants associated with body weight but the biological relevance of most remains unexplored. Given the critical role of the brain in multiple biological processes associated with body weight regulation, we set out to determine whether genetic variants linked with body mass index (BMI) could be mapped to brain proteins. Using genetic colocalization, we mapped 23 loci from the largest BMI GWAS (n=806,834) to brain proteins (obtained from a dataset of >7000 dorsolateral prefrontal cortex proteins measured by mass spectrometry in >400 individuals). We also performed a proteome-wide Mendelian randomization analysis followed by genetic colocalization, which allowed us to identify an additional 48 brain proteins linked with BMI. Multi-trait colocalization suggested that more than 75% of the protein quantitative trait loci (pQTL)-BMI associations are mediated via protein expression and not via RNA expression. Single-cell sequencing from the human brain cortex revealed that the genes expressing the proteins associated with BMI may be predominantly expressed in oligodendrocytes. In the Québec Family Study, a genetic risk score (GRS) including these brain pQTLs was associated with higher dietary carbohydrate intake and lower lipid intake whereas a GRS including the 67 variants most strongly associated with BMI was not associated with dietary intake. In conclusions, we identified 71 proteins expressed in the prefrontal cortex that may be critical regulators of body weight and possibly dietary intake in humans.
Adaptation of HL7 FHIR for the exchange of patients’ gene expression profiles
Authors: Auer Florian , Abdykalykova Zhibek , Müller Dominik , Kramer Frank
Published: February 2022

High-throughput technologies, especially gene expression analyses can accurately capture the molecular state in patients under different conditions. Thus, their application in clinical routine gains increasing relevance and fosters patient stratification towards individualized treatment decisions. Electronic health records already evolved to capture genomic data within clinical systems and standards like FHIR enable sharing within, and even between institutions. However, FHIR only provides profiles tailored to variations in the molecular sequence, while expression patterns are neglected although being equally important for decision making. Here we provide an exemplary implementation of gene expression profiles of a microarray analysis of patients with acute myeloid leukemia using an adaptation of the FHIR genomics extension. Our results demonstrate how FHIR resources can be facilitated in clinical systems and thereby pave the way for usage for the aggregation and exchange of transcriptomic data in multi-center studies.
Clinical and economic benefits of lenzilumab plus standard of care compared with standard of care alone for the treatment of hospitalized patients with Coronavirus Disease 19 (COVID-19) from the perspective of National Health Service England
Authors: Kilcoyne Adrian , Jordan Edward , Thomas Kimberly , Pepper Alicia N. , Zhou Allen , Chappell Dale , Amarapala Miyuru , Thériault Rachel-Karson , Thompson Melissa
Published: February 2022

Purpose

Estimate the clinical and economic benefits of lenzilumab plus standard of care (SOC) compared with SOC alone in the treatment of hospitalized COVID-19 patients from the National Health Service (NHS) England perspective.

Methods

A cost calculator was developed to estimate the clinical benefits and costs of adding lenzilumab to SOC in newly hospitalized COVID-19 patients over 28 days. The LIVE-AIR trial results informed the clinical inputs: failure to achieve survival without ventilation (SWOV), mortality, time to recovery, intensive care unit (ICU) admission, and invasive mechanical ventilation (IMV) use. Base case costs included drug acquisition and administration for lenzilumab and remdesivir and hospital resource costs based on level of care required. Clinical and economic benefits per weekly cohort of newly hospitalized patients were also estimated.

Results

In all populations examined, specified clinical outcomes were improved with lenzilumab plus SOC over SOC treatment alone. In a base case population aged <85 years with C-reactive protein (CRP) <150 mg/L, with or without remdesivir, adding lenzilumab to SOC was estimated to result in per-patient cost savings of £1,162. In a weekly cohort of 4,754 newly hospitalized patients, addition of lenzilumab to SOC could result in 599 IMV uses avoided, 352 additional lives saved, and over £5.5 million in cost savings. Scenario results for per-patient cost savings included: 1) aged <85 years, CRP <150 mg/L, and receiving remdesivir (£3,127); 2) Black patients with CRP <150 mg/L (£9,977); and 3) Black patients from the full population (£2,369). Conversely, in the full mITT population, results estimated additional cost of £4,005 per patient.

Conclusion

Findings support clinical benefits for SWOV, mortality, time to recovery, time in ICU, time on IMV, and ventilator use, and an economic benefit from the NHS England perspective when adding lenzilumab to SOC for hospitalized COVID-19 patients.
Mobility restrictions as a pandemic response
Authors: Lane Hakan , Şahin Mehmet , Otto Philipp
Published: February 2022

The COVID19 pandemic has caused a large number of infections and fatalities, causing administrations at various levels to use different policy measures to reduce viral spread by limiting public mobility. This paper analyzes the complex association between the stringency of restrictions, public mobility, and reproduction rate (R-value) on a national level for Germany. The goals were to analyze; a) the correlation between government restrictions and public mobility and b) the association between public mobilities and virus reproduction. In addition to correlations, a Gaussian Process Regression Technique is used to fit the interaction between mobility and R-value. The main findings are that: (i) Government restrictions has a high association with reduced public mobilities, especially for non-food stores and public transport, (ii) Out of six measured public mobilities, retail, recreation, and transit station activities have the most significant impact on COVID19 reproduction rates. (iii) A mobility reduction of 30% is required to have a critical negative impact on case number dynamics, preventing further spread.
Is chronic pain an affective disorder? Moderation of resting-state functional connectivity within the emotional brain by depressive symptoms
Authors: Quidé Yann , Norman-Nott Nell , Hesam-Shariati Negin , McAuley James H. , Gustin Sylvia M.
Published: February 2022

Background

Depressive symptoms are often comorbid to chronic pain. These conditions share aberrant emotion processing and regulation, as well as common brain networks. However, the relationship between depressive symptoms and chronic pain on emotional brain function is unclear.

Methods

Participants were 26 individuals with chronic pain (referred to as the Pain group) and 32 healthy controls (HC), who underwent resting-state functional magnetic resonance imaging and completed the Beck Depressive Inventory. Main effects of group, depressive symptom severity (total score), and their interaction were evaluated on functional connectivity from three seed regions (separately, the left and right amygdalae, the medial prefrontal cortex, mPFC) and the rest of the brain. In case of significant interaction, moderation analyses were conducted.

Results

The group-by-depressive symptoms interaction was significantly associated with changes in connectivity between the right amygdala and the mPFC (pFWEc<0.001). Moderation analysis indicated that, compared to the HC group, the Pain group showed weaker connectivity between these regions at lower levels of depressive symptoms (p=0.018), and stronger connectivity at higher levels of depressive symptoms (p=0.001). In addition, the strength of connectivity decreased in the HC (p=0.004) and increased in the Pain group (p=0.011) as the severity of depressive symptoms increased. Finally, the Pain group showed significant weaker connectivity between the mPFC seed and the left parahippocampal gyrus compared to the HC group (pFWEc=0.015).

Conclusions

These results indicate that depressive symptoms moderate the impact of chronic pain on the emotional brain function and highlight potential implications for the choice of treatment for chronic pain.
Vaccination under the Pandemic and Political Support
Authors: Takahashi Masaki , Takaku Reo , Ashida Toyo , Ibuka Yoko
Published: February 2022

This paper examines the impact of COVID-19 vaccination on political support. We exploit Japan’s age-based COVID-19 vaccine roll-out, prioritizing people aged 65 years and older. A regression discontinuity design based on a large-scale online survey reveals that COVID-19 vaccination increases favorable opinions of the vaccination progress in municipalities and infection control measures of municipal governments. By contrast, there is no significant effect on support for the central government. We also discovered that people with chronic diseases and low socioeconomic status are more affected. These results show that reciprocal motives and political information play an important role in evaluating public policies.
R-based method for quantitative analysis of biofilm thickness by using Confocal Laser Scanning Microscopy
Authors: Frühauf Hanna Marianne , Stöckl Markus , Holtmann Dirk
Published: February 2022

Microscopy is mostly the method of choice to analyse biofilms. Due to the high local heterogeneity of biofilms, single and punctual analyses only give an incomplete insight into the local distribution of biofilms. In order to retrieve statistically significant results a quantitative method for biofilm thickness measurements was developed based on confocal laser scanning microscopy and the programming language R. The R-script allows the analysis of large image volumes with little hands-on work and outputs statistical information on homogeneity of surface coverage and overall biofilm thickness. The applicability of the script was shown in microbial fuel cell experiments. It was found that G. sulfurreducens responds differently to poised anodes of different material so that the optimum potential for MFC on poised ITO anodes had to be identified with respect to maximum current density, biofilm thickness and MFC start-up time. Thereby, a positive correlation between current density and biofilm thickness was found, but with no direct link to the applied potential. The optimum potential turned out to be +0.1 V vs SHE. The script proved to be a valuable stand-alone tool to quantify biofilm thickness in a statistically valid manner, which is required in many studies.

Practical application

Biofilm communities are ubiquitous. They can be found in every habitat in which water, nutrients and a colonisable surface are present. Depending on the surface, biofilms can cause economic losses due to bio-corrosion (pipelines and ship walls are prominent examples) or are a severe threat to human health when important medical devices or body tissues are colonised [1]. Desirable biofilms are catalytic biofilms how they are used in bioelectrochemical production processes, for example. In all cases, quantitative and qualitative biofilm analysis is necessary in order to prevent or promote biofilm formation. In bioelectrochemistry quantitative biofilm analysis is essential to link productivity (current or chemicals) with biomass deposited on the electrode. Microscopic analysis (e.g. with CLSM) of stained biofilms allows the recording of high volumes of image data but often image analysis then remains at a qualitative stage. In terms of biofilm thickness determination this limits analysis to an estimated thickness of a small amount of images, mostly. The presented R-script allows the calculation of biofilm thickness based on a larger amount of image sets and allows conclusions on the homogeneity of biofilm coverage on the electrode surface. The script is a stand-alone tool if only biofilm thickness should be determined and does not require any image segmentation or processing.
Clock Work: Deconstructing the Epigenetic Clock Signals in Aging, Disease, and Reprogramming
Authors: Levine Morgan E , Higgins-Chen Albert , Thrush Kyra , Minteer Christopher , Niimi Peter
Published: February 2022

Epigenetic clocks have come to be regarded as powerful tools for estimating aging. However, a major drawback in their application is our lack of mechanistic understanding. We hypothesize that uncovering the underlying biology is difficult due to the fact that epigenetic clocks are multifactorial composites: They are comprised of disparate parts, each with their own causal mechanism and functional consequences. Thus, only by deconstructing epigenetic clock signals will it be possible to glean biological insight. Here we clustered 5,717 clock CpGs into twelve distinct modules using multi-tissue and in-vitro datasets. We show that epigenetic clocks are comprised of different proportions of modules, which may explain their discordance when simultaneously applied in a given study. We also observe that epigenetic reprogramming does not ‘reset’ the entire clock and instead the observed rejuvenation is driven by a subset of modules. Overall, two modules stand-out in terms of their unique features. The first is one of the most responsive to epigenetic reprogramming; is the strongest predictor of all-cause mortality; and shows increases with in vitro passaging up until senescence burden begins to emerge. The light-second module is moderately responsive to reprogramming; is very accelerated in tumor vs. normal tissues; and tracks with passaging in vitro even as population doublings decelerate. Overall, we show that clock deconstruction can identify unique DNAm alterations and facilitate our mechanistic understanding of epigenetic clocks.
Glutamate indicators with improved activation kinetics and localization for imaging synaptic transmission
Authors: Aggarwal Abhi , Liu Rui , Chen Yang , Ralowicz Amelia J , Bergerson Samuel J , Tomaska Filip , Hanson Timothy L , Hasseman Jeremy P , Reep Daniel , Tsegaye Getahun , Yao Pantong , Ji Xiang , Kloos Marinus , Walpita Deepika , Patel Ronak , Mohr Manuel A , Tilberg Paul W , Mohar Boaz ,   The GENIE Project Team, Looger Loren L , Marvin Jonathan S , Hoppa Michael B , Konnerth Arthur , Kleinfeld David , Schreiter Eric R , Podgorski Kaspar
Published: February 2022

The fluorescent glutamate indicator iGluSnFR enables imaging of neurotransmission with genetic and molecular specificity. However, existing iGluSnFR variants exhibit saturating activation kinetics and are excluded from post-synaptic densities, limiting their ability to distinguish synaptic from extrasynaptic glutamate. Using a multi-assay screen in bacteria, soluble protein, and cultured neurons, we generated novel variants with improved kinetics and signal-to-noise ratios. We also developed surface display constructs that improve iGluSnFR’s nanoscopic localization to post-synapses. The resulting indicator, iGluSnFR3, exhibits rapid non-saturating activation kinetics and reports synaptic glutamate release with improved linearity and increased specificity versus extrasynaptic signals in cultured neurons. In mouse visual cortex, imaging of iGluSnFR3 at individual boutons reported single electrophysiologically-observed action potentials with high specificity versus non-synaptic transients. In vibrissal sensory cortex Layer 4, we used iGluSnFR3 to characterize distinct patterns of touch-evoked feedforward input from thalamocortical boutons and both feedforward and recurrent input onto L4 cortical neuron dendritic spines.
Heart rate variability as biomarker for bipolar disorder
Authors: Stautland Andrea , Jakobsen Petter , Fasmer Ole Bernt , Osnes Berge , Torresen Jim , Nordgreen Tine , Oedegaard Ketil J
Published: February 2022

Bipolar disorder (BD) is characterized by alterations in mood, energy levels and the ability to function. Accordingly, it is also associated with dysfunction of the autonomic nervous system (ANS), indexed by heart rate variability (HRV). Literature concerning differences in ANS functioning between mood states is still sparse. The main aim of the study was to investigate within-individual changes in HRV from manic to euthymic states in bipolar disorder (BD). This is the first study to do so using wrist-worn sensors. Seventeen patients with BD were equipped with photoplethysmography (PPG) sensor wristbands and provided 24-hour recordings both during a manic state and a euthymic state. We calculated mean heart rate and the commonly used HRV measures SDNN, RMSSD, HF, LF and Sample Entropy in 5-minute segments during rest at night. We compared HRV by mood state within individuals using paired t-tests and linear regression to control for age and sex. Recordings from 15 BD patients were analyzed. There were statistically significant increases in HRV measures SDNN, RMSSD, LF and Sample Entropy from mania to euthymia. Effect sizes were predominately large. Our findings reveal lower HRV in the manic state compared to the euthymic state. This indicates that HRV collected by wrist-worn PPG sensors is a possible biomarker for bipolar mood states. Movement artifacts were problematic and sampling during rest or in combination with actigraphy is recommended. Our findings can be further implemented to develop a monitoring device for bipolar patients.
Neuroimmune transcriptome changes in brains of psychiatric and neurological disorder patients
Authors: Chen Yu , Dai Jiacheng , Tang Longfei , Mikhailova Tatiana , Liang Qiuman , Li Miao , Zhou Jiaqi , Weickert Cynthia , Chen Chao , Liu Chunyu
Published: February 2022

Neuroinflammation has been implicated in multiple brain disorders but the extent and the magnitude of change in immune-related genes (IRGs) across distinct brain disorders has not been directly compared. We curated 1,275 IRGs and investigated their expression changes in 2,467 postmortem brains of controls and patients with six major brain disorders, including schizophrenia (SCZ), bipolar disorder (BD), autism spectrum disorder (ASD), major depressive disorder (MDD), Alzheimer’s disease (AD), and Parkinson’s disease (PD). More than 60% of the IRGs had significantly altered expression in at least one of the six disorders. The differentially expressed immune-related genes (dIRGs) shared across disorders were mainly related to innate immunity. Moreover, we systematically evaluated sex, tissue, and cell type for immune alterations in different neuropsychiatric disorders. Co-expression networks revealed that neuroimmune systems interacted with neuronal-systems, both of which contribute to the risk of disorders. However, only a few genes with expression changes have also been identified as containing risk variants of genome-wide association studies. The transcriptome alterations at gene and network levels may clarify the immune-related pathophysiology and redefine neuropsychiatric and neurological disorders.

One-Sentence Summary

The brain transcriptome of six neurological and psychiatric disorders showed signature changes in genes related to immunity.
Increased neutralization and IgG epitope identification after MVA-MERS-S booster vaccination against Middle East respiratory syndrome
Authors: Fathi Anahita , Dahlke Christine , Krähling Verena , Kupke Alexandra , Okba Nisreen M. A. , Raadsen Matthijs P. , Heidepriem Jasmin , Müller Marcel A. , Paris Grigori , Lassen Susan , Klüver Michael , Volz Asisa , Koch Till , Ly My L. , Friedrich Monika , Fux Robert , Tscherne Alina , Kalodimou Georgia , Schmiedel Stefan , Corman Victor M. , Hesterkamp Thomas , Drosten Christian , Loeffler Felix F. , Haagmans Bart L. , Sutter Gerd , Becker Stephan , Addo Marylyn M.
Published: February 2022

Vaccine development is essential for pandemic preparedness. We previously conducted a Phase 1 clinical trial of the vector vaccine candidate MVA-MERS-S against the Middle East respiratory syndrome coronavirus (MERS-CoV), expressing its full spike glycoprotein (MERS-CoV-S), as a homologous two-dose regimen (Days 0 and 28). Here, we evaluate a third vaccination with MVA-MERS-S in a subgroup of trial participants one year after primary immunization. A booster vaccination with MVA-MERS-S is safe and well-tolerated. Both binding and neutralizing anti-MERS-CoV antibody titers increase substantially in all participants and exceed maximum titers observed after primary immunization more than 10-fold. We identify four immunogenic IgG epitopes, located in the receptor-binding domain (RBD, n=1) and the S2 subunit (n=3) of MERS-CoV-S. The level of baseline anti-human coronavirus antibody titers does not impact the generation of anti-MERS-CoV antibody responses. Our data support the rationale of a booster vaccination with MVA-MERS-S and encourage further investigation in larger trials.

One Sentence Summary

A late booster vaccination with the vector vaccine MVA-MERS-S against MERS-CoV is safe and significantly increases humoral immunogenicity including responses to four IgG epitopes.
Class 1 integrons in clinical and swine industry isolates of Salmonella Typhimurium from Colombia, dating 1997 to 2017
Authors: Flórez-Delgado Nancy Yaneth , Ubillus Elizabeth Noelia , Perez-Sepulveda Blanca , Ospina-Ríos Eyda Lizeth , Carrascal-Camacho Ana Karina , Chamorro-Tobar Iliana C , Montaño Lucy Angeline , Li Yan , Zapata-Bedoya Silvana , Hinton Jay C.D. , Villarreal José Miguel , Wiesner Magdalena
Published: February 2022

Background

Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium) has been linked to outbreaks of foodborne gastroenteritis disease, and the emergence of antimicrobial-resistant clones. In Colombia, laboratory surveillance of Salmonella spp. between 1997-2018 revealed that S. Typhimurium was the most ubiquitous serovar (27.57% of all Salmonella isolates), with increasing levels of antimicrobial resistance to several families of antibiotics. Hypothesis. Resistant isolates of S. Typhimurium recovered from clinical and swine samples carry class 1 integrons that are linked to antimicrobial resistance genes. Aim. Identify class 1 integrons, and investigate their association with other mobile genetic elements, and their relationship to the antimicrobial resistance of Colombian S. Typhimurium isolates. Methods. In this study, 392 clinical isolates of S. Typhimurium were analyzed, of which 237 were obtained from blood culture, 155 from non-invasive sources and 50 isolates from swine of which 32 were obtained from a slaughterhouse, 10 from a point of sale and 8 from cutting plant. Class 1 integrons and plasmid incompatibility groups were analyzed by PCR and Whole Genome Sequencing (WGS), and the region surrounding of the integrons identified by WGS. The phylogenetic relationship was established by MLST and SNP analysis. Results. Overall, 39.03% (153/392) of the clinical isolates and 22% (11/50) of the swine S. Typhimurium isolates carried complete class 1 integrons. Twelve types of gene cassette arrays were identified, including dfr7-aac-blaOXA-2 (Int1-Col1) as the most frequent in clinical isolates (75.2% = 115/153). Clinical and swine isolates that carried class 1 integrons were resistant to up to 5 and up to 3 antimicrobial families, respectively. The Int1-Col1 integron was most prevalent in stool isolates and was associated with Tn21. The most common plasmid incompatibility group was IncA/C. Conclusions. The widespread presence of the integron (IntI1-Col1) in Colombia since 1997 was striking. We speculate that the relationship between integrons, source and mobile elements favors the dispersion of antibiotic resistance determinants in Colombian S. Typhimurium isolates.
RESIDENTS’ PERCEPTION ON CENTRAL STORAGE OF SOLID WASTES IN ILORIN METROPOLIS, KWARA STATE. NIGERIA
Authors: Raufu Yusuf Olanrewaju , Olayinka Adewoye Solomon , Olawale Sawyerr Henry
Published: February 2022

Background

Solid waste management in Nigeria has been a major concern to stakeholders due to inefficient collection and unsafe disposal. In Ilorin, the capital of Kwara state, the problem of wastes is becoming alarming because the more these wastes are evacuated the more they are generated on a daily basis. Thus, the issue of central storage of solid waste situation in Ilorin to say the least, is becoming quite distressing.

Objectives

This study addressed issues relating to waste management and perception of residence to central waste storage in Ilorin metropolis.

Methods

A cross-sectional study was conducted among the residents in the three local government that constitute Ilorin metropolis, residents living close to central wastes storages in Ilorin metropolis are purposively chosen and the registered wastes contractors with the Kwara State Environmental Protection Agency (KWASEPA). In accomplishing these objectives, both primary and secondary data sources were used. The primary data were collected via questionnaires and field observations. Secondary data were extracted from different published and unpublished materials. 120 households located on the main road and close to central wastes storage bins and 30 wastes contractors are administered with questionnaires. The data were analyzed using statistical package for social science (SPSS version 23) for descriptive and inferential at 5% level of significance.

Results

The operational capacities of wastes contractors showed a low capacity as 66.7% (20) operate with single rickety truck. Dumpsites accessibility and insufficiency is an impediment as the dumpsite was found to be too far and largely inaccessible. Condition of wastes spillage from the central storage and storage on the road meridians are draw backs to effective wastes management and majority of respondents 66.7% are unhappy.

Conclusions

It was discovered that central wastes storage system in Ilorin metropolis was not effective with constant incidence of wastes spillages and storage on road meridians. Therefore, capacity and competence should be considered in wastes management contract award, provision of more central wastes storage, establishing wastes transfer station, provision of adequate dumpsites at different local government, public enlightenment, regular trainings for wastes consultant, provision of loans for wastes consultants for acquisition of trucks and proper monitoring by regulatory agency will ensure a clean and sanitary environment in the metropolis.
Bayesian Space-time SIR modeling of Covid-19 in two US states during the 2020-2021 pandemic
Authors: Lawson Andrew B , Kim Joanne
Published: February 2022

This paper describes the Bayesian SIR modeling of the 3 waves of Covid-19 in two contrasting US states during 2020-2021. A variety of models are evaluated at the county level for goodness-of-fit and an assessment of confounding predictors is also made. It is found that models with three deprivation predictors and neighborhood effects are important. In addition, the work index from Google mobility was also found to provide an increased explanation of the transmission dynamics.
Prediction Model for Detection of Sporadic Pancreatic Cancer (PRO-TECT) in a Population-Based Cohort Using Machine Learning and Further Validation in a Prospective Study
Authors: Chen Wansu , Zhou Yichen , Xie Fagen , Butler Rebecca K. , Jeon Christie Y. , Luong Tiffany Q. , Lin Yu-Chen , Lustigova Eva , Pisegna Joseph R. , Kim Sungjin , Wu Bechien U.
Published: February 2022

OBJECTIVES

There is currently no widely accepted approach to screening for pancreatic cancer (PC). We aimed to develop and validate a risk prediction model for PC across two health systems using electronic health records (EHR).

METHODS

This retrospective cohort study consisted of patients 50-84 years of age meeting utilization criteria in 2008-2017 at Kaiser Permanente Southern California (KPSC, model training, internal validation) and the Veterans Affairs (VA, external validation). ‘Random survival forests’ models were built to identify the most relevant predictors from >500 variables and to predict PC within 18 months of cohort entry. A prospective study was then conducted in KPSC to assess feasibility of the model for real-time implementation.

RESULTS

The KPSC cohort consisted of 1.8 million patients (mean age 61.6) with 1,792 PC cases. The estimated 18-month incidence rate of PC was 0.77 (95% CI 0.73-0.80)/1,000 person-years. The three models containing age, abdominal pain, weight change and two laboratory biomarkers (ALT change/HgA1c, rate of ALT change/HgA1c, or rate of ALT change/rate of HgA1c change) had comparable discrimination and calibration measures (c-index: mean=0.77, SD=0.01-0.02; calibration test: p-value 0.2-0.4, SD 0.2-0.3). The VA validation cohort consisted of 2.6 million patients (mean age 66.1) with an 18-month incidence rate of 1.27 (1.23-1.30). A total of 606 patients were screened in the prospective pilot study at KPSC with 9 patients (1.5%) diagnosed with a pancreatic or biliary cancer.

CONCLUSIONS

Using widely available parameters in EHR, we developed a population-based parsimonious model for early detection of sporadic PC suitable for real-time application.

Study Highlights

What Is Known

Patients with pancreatic cancer are often diagnosed at late stages.

Early detection is needed to impact the natural history of disease progression and improve patient survival.

What Is New Here

Machine-learning was used to develop a population-based model for early detection of pancreatic cancer. The model was internally and externally validated in cohorts of 1.8 million and 2.6 million individuals, respectively.

Calibration was excellent in prospective pilot testing for detection of pancreatic malignancy.
Cost-effectiveness of Ezetimibe plus statin lipid-lowering therapy: A systematic review and meta-analysis of cost-utility studies
Authors: Sasidharan Akhil , Kumar S Sajith , Jagadeesh Kayala Venkata , Natarajan Meenakumari , Bagepally Bhavani Shankara
Published: February 2022

Introduction

In addition to statin therapy, Ezetimibe, a non-statin lipid-modifying agent, is increasingly used to reduce low-density lipoprotein cholesterol and atherosclerotic cardiovascular disease risk. Literature suggests the clinical effectiveness of Ezetimibe plus statin (EPS) therapy; however, primary evidence on its economic effectiveness is inconsistent. Hence we pooled incremental net benefit to synthesise the cost-effectiveness of EPS therapy.

Methods

We identified economic evaluation studies reporting outcomes of EPS therapy compared with other lipid-lowering therapeutic agents or placebo by searching PubMed, Embase, Scopus, and Tufts Cost-Effective Analysis registry. Using random-effects meta-analysis, we pooled Incremental Net Benefit (INB) in the US $ with a 95% confidence interval (CI). We used the modified economic evaluations bias checklist and GRADE quality assessment for quality appraisal. The review was apriori registered with PROSPERO, CRD42021248531.

Results

The pooled INB from twenty-one eligible studies showed that EPS therapy was significantly cost-effective compared to other lipid-lowering therapeutic agents or placebo. The pooled INB (95% CI) was $4,274 (621 to 7,927), but there was considerable heterogeneity (I2=84.21). On subgroup analysis EPS therapy is significantly cost-effective in high-income countries [$4,356 (621 to 8,092)], for primary prevention [$4,814 (2,523 to 7,106)], and for payers’ perspective [$3,255 (571 to 5,939)], and from lifetime horizon [$4,571 (746 to 8,395)].

Conclusion

EPS therapy is cost-effective compared to other lipid-lowering therapeutic agents or placebo in high-income countries and for primary prevention. However, there is a dearth of evidence from lower-middle-income countries and the societal perspective.
Heterogeneity impacts biomarker discovery for precision medicine
Authors: Smith Kenneth , Climer Sharlee
Published: February 2022

Precision medicine is advancing patient care for complex human diseases. Discovery of biomarkers to diagnose specific subtypes within a heterogeneous diseased population is a key step towards realizing the benefits of precision medicine. However, popular statistical methods for evaluating candidate biomarkers – fold change (FC) and area under the receiver operating characteristic curve (AUC) – were designed for homogeneous data. Herein, we evaluate the performance of these metrics in heterogeneous populations. Using simulated biomarkers that are nearly ‘ideal’ for distinguishing subgroups of various proportions of the diseased population, we observe that AUC misses all up to subset size of 50% and FC misses all biomarkers entirely. We introduce a simple new measure to address this shortfall and run a series of trials comprised of simulated and biological data to demonstrate its utility for evaluating biomarkers associated with disease subtypes.
Predicting vertical ground reaction forces from 3D accelerometry using reservoir computers leads to accurate gait event detection
Authors: Bach Margit M. , Dominici Nadia , Daffertshofer Andreas
Published: February 2022

Accelerometers are low-cost measurement devices that can readily be used outside the lab. However, determining isolated gait events from accelerometer signals, especially foot-off events during running, is an open problem. We outline a two-step approach where machine learning serves to predict vertical ground reaction forces from accelerometer signals, followed by force-based event detection.

We collected shank accelerometer signals and ground reaction forces from 21 adults during comfortable walking and running on an instrumented treadmill. We trained one common reservoir computer using segmented data using both walking and running data. Despite being trained on just a small number of strides, this reservoir computer predicted vertical ground reaction forces in continuous gait with high quality. The subsequent foot contact and foot off event detection proved highly accurate when compared to the golden standard based on co-registered ground reaction forces. Our proof-of-concept illustrates the capacity of combining accelerometry with machine learning for detecting isolated gait events irrespective of mode of locomotion.
OsIRO3 negatively regulates Fe homeostasis by repressing the expression of OsIRO2
Authors: Li Chenyang , Li Yang , Xu Peng , Liang Gang
Published: February 2022

Iron (Fe) is crucial for crop productivity and quality. However, Fe deficiency is prevalent worldwide, especially in alkaline soil. Plants have evolved sophisticated mechanisms to withstand Fe deficiency conditions. Oryza sativa IRON-RELATED BHLH TRANSCRIPTION FACTOR 3 (OsIRO3/OsbHLH63) has been identified as a negative regulator of Fe deficiency response signaling, however, the underlying mechanism remains unclear. In the present study, we constructed two iro3 mutants which generated leaves with necrotic lesions under Fe deficient conditions. Loss-of-function of OsIRO3 caused upregulation of Fe deficiency-associated genes in the root under Fe deficient conditions. Fe concentration measurement showed that the iro3 mutants had increased shoot Fe concentration only under Fe deficient conditions. Further analysis revealed that OsIRO3 directly regulated the expression of IRON-RELATED BHLH TRANSCRIPTION FACTOR 2 (OsIRO2) which encodes a positive regulator of Fe uptake system. Protein interaction tests indicated that OsIRO3 interacted with OsPRI1 and OsPRI2. Further investigation demonstrated that OsIRO3 repressed the transactivation of OsPRI1 and OsPRI2 towards OsIRO2. OsIRO3 contains an EAR motif which recruits the TOPLESS/TOPLESS-RELATED (OsTPL/OsTPRs) corepressors. Mutation of the EAR motif attenuated the repression ability of OsIRO3. This work sheds light on the molecular mechanism by which OsIRO3 modulates Fe homeostasis in rice.
Super-resolution analyzing spatial organization of lysosomes with an organic fluorescent probe
Authors: Wang Lei , Chen Rui , Han Guanqun , Liu Xuan , Huang Taosheng , Diao Jiajie , Sun Yujie
Published: February 2022

Lysosomes are multifunctional organelles involved in macromolecule degradation, nutrient sensing and autophagy. Live imaging has revealed lysosome subpopulations with dynamics and characteristic cellular localization. An as-yet unanswered question is whether lysosomes are spatially organized to coordinate and integrate their functions. Combined with super-resolution microscopy, we designed a small organic fluorescent probe, TPAE, that targeted lysosomes with a large Stokes shift. When we analyzed the spatial organization of lysosomes against mitochondria in different cell lines with this probe, we discovered different distance distribution patterns between lysosomes and mitochondria during increased autophagy flux. By usingSLC25A46mutation fibroblasts derived from patients containing highly fused mitochondria with low oxidative phosphorylation, we concluded that unhealthy mitochondria redistributed the subcellular localization of lysosomes, which implies a strong connection between mitochondria and lysosomes.
Early zygotic gene product Dunk interacts with anillin to regulate Myosin II during Drosophila cleavage
Authors: Chen Jiayang , He Bing
Published: February 2022

Drosophila cellularization is a special form of cleavage that converts syncytial embryos into cellular blastoderms by partitioning the peripherally localized nuclei into individual cells. An early event in cellularization is the recruitment of non-muscle myosin II (“myosin”) to the basal tip of cleavage furrows, where myosin forms an interconnected basal array before reorganizing into individual cytokinetic rings. The initial recruitment and organization of basal myosin are regulated by a cellularization-specific gene, dunk, but the underlying mechanism is unclear. Through a genome-wide yeast two-hybrid screen, we identified anillin (Scraps in Drosophila), a conserved scaffolding protein in cytokinesis, as the primary binding partner of Dunk. We show that Dunk regulates the localization of anillin at the cleavage furrows during early cellularization and functionally interacts with anillin in regulating basal myosin. Furthermore, we show that anillin colocalizes with myosin since the onset of cellularization and is required for the initial recruitment and maintenance of myosin at the basal array, prior to the well-documented function of anillin in regulating cytokinetic ring assembly. Based on these results, we propose that Dunk regulates myosin recruitment and organization during early cellularization by interacting with and regulating anillin.
Accurate models of substrate preferences of post-translational modification enzymes from a combination of mRNA display and deep learning
Authors: Vinogradov Alexander A. , Chang Jun Shi , Onaka Hiroyasu , Goto Yuki , Suga Hiroaki
Published: February 2022

Promiscuous post-translational modification (PTM) enzymes often display non-obvious substrate preferences by acting on diverse yet well-defined sets of peptides and/or proteins. Thorough understanding of substrate fitness landscapes for promiscuous PTM enzymes is important because they play key roles in many areas of contemporary science, including natural product biosynthesis, molecular biology and biotechnology. Here, we report the development of an integrated platform for accurate profiling of substrate preferences for PTM enzymes. The platform features a combination of i) mRNA display with next generation sequencing as an ultrahigh throughput technique for data acquisition and ii) deep learning for data analysis. The high accuracy (>0.99 in each of two studies) and generalizability of the resulting deep learning models enables comprehensive analysis of enzymatic substrate preferences. The models can be utilized to quantify fitness across sequence space, map modification sites, and identify important amino acids in the substrate. To benchmark the platform, we perform substrate specificity profiling of a Ser dehydratase (LazBF) and a Cys/Ser cyclodehydratase (LazDEF), two enzymes from the lactazole biosynthesis pathway. In both studies, our results point to highly complex enzymatic preferences, which, particularly for LazBF, cannot be reduced to a set of simple rules. The ability of the constructed models to dissect and analyze such complexity suggests that the developed platform can facilitate the wider study of PTM enzymes.
The interplay between sulfur metabolism and desulfurization profile in Rhodococcus: Unraveling the role of the transsulfuration pathway
Authors: Martzoukou Olga , Glekas Panayiotis , Avgeris Margaritis , Mamma Diomi , Scorilas Andreas , Kekos Dimitris , Amillis Sotiris , Hatzinikolaou Dimitris G.
Published: February 2022

Biodesulfurization (BDS) is a process that selectively removes sulfur from dibenzothiophene and its derivatives. Several natural biocatalysts have been isolated, all harboring the highly conserved desulfurization operon dszABC. Even though the desulfurization phenotype is known to be significantly repressed by methionine, cysteine, and inorganic sulfate, the available information on the metabolic regulation of gene expression is still limited. In this study, scarless knockouts of the sulfur metabolism-related cbs and metB genes are constructed in the desulfurizing strain Rhodococcus sp. IGTS8. We provide sequence analyses for both enzymes of the reverse transsulfuration pathway and report their involvement in the sulfate- and methionine-dependent repression of the biodesulfurization phenotype, based on desulfurization assays in the presence of different sulfur sources. Additionally, the positive effect of cbs and metB gene deletions on dsz gene expression in the presence of both sulfate and methionine, but not cysteine, is uncovered and highlighted.