bluuebunny/crossref_metadata_2025_split huggingface dataset:
An interdisciplinary approach to reveal the dynamics of generalized transduction of antimicrobial resistance genes
Authors: Leclerc Quentin , Gupta Arya , Lindsay Jodi , Knight Gwenan 
Published: May 2022

Background
Antimicrobial resistance (AMR) genes can spread between bacteria by “generalized transduction”, where phages act as vectors to transfer them. However, our knowledge of the dynamics of transduction and how to best represent them is limited. We aimed to fill this gap through an interdisciplinary approach, generating microbiological data and using mathematical models to clarify the underlying transduction dynamics.

Methods
We co-cultured two library strains of Methicillin-resistantStaphylococcus aureus, each harbouring a resistance gene for a different antibiotic, with 80α generalized transducing phage. We recorded numbers of bacteria and phages at multiple time-points over 24h, using the presence of bacteria resistant to both antibiotics as evidence that transduction occurred. We developed and compared mathematical models of transduction based on how well they fit to the lab data.

Results
After a growth phase of 8h, bacteria and phage surprisingly coexisted at a stable equilibrium in our culture, the level of which was dependent on the initial concentration of phage. The rate of transducing phage generation was approximately 10-6per lytic phage, sufficient to consistently generate double resistant bacteria, detectable after only 7h. Dynamics of transduction were best captured by a mathematical model in which the rate of phage infection slows as the bacteria population approaches carrying capacity.

Conclusions
The novel data and models generated provide valuable insights into the dynamics of transduction of AMR. This interdisciplinary framework could be extended to other bacterial species, and is the first step towards evaluating the impact of transduction on the overall public health consequences of AMR.
Immuno-proteomics of sera from gonorrhoea patients identified potential vaccine candidates
Authors: Dijokaite-Guraliuc Aiste , Humbert Victoria Maria , Skipp Paul , Christodoulides Myron 
Published: May 2022

Gonorrhea is a sexually transmitted disease caused by Neisseria gonorrhoeae and is one of the leading reportable STDs in adults, with ~87 million cases annually and globally. Gonorrhoea remains a major global public health concern not only because of rising incidence each year, but also because of rising antimicrobial resistance. There is an urgent need for long-term solutions to prevent gonorrhoea such as vaccines, but none currently existand research is focused on identifying potential antigens for inclusion in new vaccines. In our study, we used an immuno-proteomics approach to try and identify potential vaccine candidates.
A heterologous N. gonorrhoeae strain P9-17 was grown under iron-limiting conditions and whole cell lysates prepared. These were separated by isoelectric focusing (pH 3-10 range) and fractions were separated by SDS-PAGE. Western blots were prepared and reacted with sera from 20 patients with uncomplicated gonorrhoea and with sera from 5 controls with no history of gonorrhoea. Immuno-reactive bands were excised from the corresponding gels and subjected to mass spectrometry, which provided a profile of gonococcal proteins. After comparing patterns of reactivity, we identified 180 bands in sera from gonorrhoea patients. Using a bio-informatics approach we refined the list to 18 bands of interest and identified 13 novel proteins associated with an increase in immuno-reactivity with gonococci.
In summary, we have identified a unique set of gonococcal proteins that have not yet been investigated as potential vaccine antigens and that are the focus of current studies to develop a gonococcal vaccine.
Investigation of the impact of food preservatives on avian pathogenicEscherichia coli(APEC) and their role in driving zoonotic disease
Authors: Fallata Ghaith , Wall Donal 
Published: May 2022

The excessive use of antibiotics in agriculture is routinely described as a major contributor to bacterial antimicrobial resistance. Globally, antibiotics are also widely used as growth supplements in livestock. This has led to concerns regarding use of human-use antibiotics in food and food-producing animals. In more recent times organic acids such as propionic acid (PA) and formic acid (FA) have been used as alternative antimicrobials or preservatives in place of antibiotics.
PA is a short chain fatty acid naturally abundant in the human and animal intestine as a breakdown product of non-digestible carbohydrates. In the human intestine it plays important roles in regulating the immune response in the human body. Recently, a study has shown that exposure of a Crohn’s Disease associated bacterial pathotype, adherent-invasive Escherichia coli(AIEC),to PA significantly altered its phenotype resulting in increased adhesion and invasion of epithelial cells and increased persistence through biofilm-formation.
AIEC are both evolutionarily and phylogenetically related to avian pathogenicEscherichia coli (APEC). PA and FA use is widespread in chickens a known source of zoonotic disease. Our results indicate that virulence of some APEC strains is increased by exposure to alternative antimicrobials such as PA and FA. This included increased adhesion of APEC strain E. coli 601 to human intestinal epithelial cells after exposure to FA which could be a potential risk of zoonotic disease. Further investigation of APEC strains is currently underway in a fermentation model of the poultry gut. This approach will improve our understanding of how commonly used.
Respiratory pathogens co-infection in patients with COVID-19 pneumonia in Kazakhstan
Authors: Lavrinenko Alyona , Kolesnichenko Svetlana , Turmukhambetova Anar , Kadyrova Irina 
Published: May 2022

Background
Clinical evidence of the presence of bacterial co-infection in patients with SARS-CoV-2 pneumonia is important for an adequate treatment with antibacterial drugs. Objectives: to determine the secondary bacterial flora in patients with COVID pneumonia in patients in the Republic of Kazakhstan.

Methods
Prospective, microbiological, multicenter study, which was conducted at the Medical University of Karaganda in the Shared Resource Laboratory. Sputum samples were collected from three cities of Kazakhstan with the worst SARS-CoV-2 epidemiological situation. Microbiological examination was carried out using classical methods. All investigated isolates were identified to species by MALDI-TOF mass spectrometry. Susceptibility to antibiotics was performed by the disk diffusion method in accordance with the CLSI 2019 recommendations.

Results
133 patients were included with a mean age of 60.9±12.7 years old, 53/133 (39.8%) had confirmed SARS-CoV-2 PCR test. Microbiological examination showed the growth of normal microflora in 31.45%. Difference in secondary bacterial co-infection etiology in COVID-19 positive and negative patients was not found. The leading place in general etiological structure belonged to K.pneumoniae - 22.64%, E.coli - 11.95% and A.baumannii - 11.32%. A significant relationship (p = 0.003) between such parameters as the use of antibacterial drugs and the isolated microflora was found.

Conclusions
Isolated microorganisms are etiologically significant and are pathogens of the ESKAPE group. It is important to limit the risk of infection and spread of resistant microorganisms by closely monitoring nosocomial infections and drawing attention to secondary infections caused by resistant bacteria that can increase the mortality rate of patients with COVID-19.
Signatures of defective DNA repair and replication in early-onset renal cancer patients referred for germline genetic testing
Authors: Demidova Elena V. , Serebriiskii Ilya G. , Vlasenkova Ramilia , Kelow Simon , Andrake Mark D. , Hartman Tiffiney R. , Kent Tatiana , Pomerantz Richard T. , Dunbrack Roland L. , Golemis Erica A. , Hall Michael J. , Chen David Y.T. , Daly Mary B. , Arora Sanjeevani 
Published: May 2022

AbstractEarly-onset renal cell carcinoma (eoRCC) is typically associated with pathogenic germline variants (PGVs) in RCC familial syndrome genes. However, most eoRCC patients lack PGVs in familial RCC genes and their genetic risk remains undefined. Here, we analyzed biospecimens from 22 eoRCC patients that were seen at our institution for genetic counseling and tested negative for PGVs in RCC familial syndrome genes. We performed whole-exome sequencing (WES) and found enrichment of candidate pathogenic germline variants in DNA repair and replication genes, including multiple DNA polymerases. Induction of DNA damage in peripheral blood monocytes (PBMCs) significantly elevated numbers of γH2AX foci, a marker of double-stranded breaks, in PBMCs from eoRCC patients versus PBMCs from matched cancer-free controls. Knockdown of candidate PGVs in Caki RCC cells increased γH2AX foci. Immortalized patient-derived B cells bearing candidate PGVs in DNA polymerase genes (POLD1, POLH, POLE, POLK) had DNA replication defects compared to control cells. Renal tumors carrying these DNA polymerase variants were microsatellite stable but had a high mutational burden. Direct biochemical analysis of the variant Pol δ and Pol η polymerases revealed defective enzymatic activities. Together, these results suggest that constitutional defects in DNA repair such as DNA replication repair underlie a subset of eoRCC cases. These findings may provide opportunities for use of the DNA repair targeting agents for eoRCC treatment. Screening patient lymphocytes to identify these defects may provide insight into mechanisms of carcinogenesis in a subset of genetically undefined eoRCCs.Significance StatementScreening for DNA repair variation may provide a more comprehensive risk assessment for eoRCC patients. Evaluation of DNA repair defects may also provide insight into the cancer initiation mechanisms for subsets of eoRCCs and lay the foundation for targeting DNA repair vulnerabilities in eoRCC.
Behavioral Responses to Fevers and Other Medical Events in Children With and Without ASD
Authors: Byrne Katherine , Zheng Shuting , Bishop Somer , Boucher Juliana , Ghods Sheila , Kim So Hyun , Lord Catherine 
Published: May 2022

AbstractObjectiveAnecdotal reports and a small number of research studies suggest possible behavioral improvements in children with autism spectrum disorders (ASD) during a fever. However, previous studies rely largely on retrospective reports of this phenomenon. Establishing a robust association between fever and reduction of ASD-related symptoms would promote opportunities for the development of innovative therapeutic interventions for children with ASD.MethodsProspective data were collected from 141 children with ASD and 103 typically developing (TD) controls using parent responses to an 11-item behavioral survey. Behaviors when no illness was present, during a fever, the week after a fever, and during non-febrile illnesses for TD and ASD children were compared. Profiles of cases in which caregivers reported consistent behavioral improvements during fever are described.ResultsData indicated worsening social, emotional/behavioral, and somatic symptoms during a fever regardless of diagnosis, with children with ASD demonstrating greater worsening of behaviors during a fever than TD children. Three children (all with ASD) out of 244 demonstrated consistent behavioral improvements during a fever; these children had a range of cognitive and adaptive skills.ConclusionsChildren with ASD had stronger negative responses to fever than TD children. These findings contradict previous literature suggesting behavioral improvements for children with ASD. While improvements may occur for some children, it does not appear to be a common phenomenon. Additional research is needed to elucidate the nature of behavioral improvements in the subset of children with ASD who may respond positively to fever.Article SummaryThis study examines behavioral changes during fever and other medical events in children with autism compared to behavioral changes in a typically developing control group.What’s Known on this SubjectPrevious research and consistent anecdotal reports suggest the possibility of behavioral improvements for children with autism during a fever. There is a dearth of prospectively collected data examining these effects.What This Study AddsChildren with autism consistently had stronger and more frequent negative behavior changes during fever than typical children who also primarily showed worsening of behavior during fevers. Three autistic children, and no typical children, showed improvements in varied areas during fevers.
Both vascular risk factors and common genetic variants influence penetrance of variants causing monogenic stroke
Authors: Cho Bernard PH , Harshfield Eric L , Al-Thani Maha , Tozer Daniel J , Bell Steven , Markus Hugh S 
Published: May 2022

ABSTRACTMonogenic forms of stroke have been thought to be rare with high penetrance. However, recent studies have reported typical monogenic stroke pathogenic variants are much commoner than expected in the general population. Whether such variants are associated with disease, and why the phenotype of these variants varies so widely remain unclear. In 454,787 individuals in UK Biobank, we identified typical pathogenic variants in NOTCH3, HTRA1 and COL4A1/2 genes in 1 in 467, 1 in 832 and 1 in 1353 subjects, respectively. Variants in all three genes were associated with stroke risk, and NOTCH3 and HTRA1 with dementia risk. Cardiovascular risk (assessed by Framingham cardiovascular risk score), polygenic risk (assessed by a polygenic stroke risk score), and variant location within each gene, were all associated with penetrance of NOTCH3 and HTRA1 variants. Our results suggest intensive cardiovascular risk factor modification may reduce stroke and dementia risk in individuals with such variants.
Concurrent malaria and dengue fever in (sub-Saharan) Africa: a systematic review and meta-analysis
Authors: Gebremariam Tewelde T. , Mekonnen Zeleke , Danquah Jonas B. 
Published: May 2022

ABSTRACTObjectivesTo determine the prevalence of concurrent malaria and dengue fever, aetiologies, and the association between the two infections in Africa.MethodsWe assessed evidence from previous studies in Africa that were available in MEDLINE and EMBASE databases between January 01, 2005, and March 30, 2022.ResultsA total of 3942 studies were identified from the databases of which 30 studies from 13 African countries, including 25,241 febrile patients, were included in the meta-analysis. The result of the meta□analysis showed a 4.0% pooled prevalence of concurrent malaria and dengue fever in (sub-Saharan) Africa, and the highest rate was recorded in Central Africa (5.8%) followed by East Africa (4.7%) and West Africa (2.8%). Children <18 years old (57%) and females (52.8%) were more affected by the co-infection than adults and females, respectively. The dengue virus serotypes identified were DENV-2, DENV-3, DENV-1, and DENV-4 in descending order with a proportion of 39%, 31%, 27%, and 3%, respectively. Moreover, Plasmodium falciparum was the only specified malaria parasite in the co-infection among the included studies. Significantly higher odds of malaria infection were documented due to dengue fever when compared with malaria mono-infection. However, no significant odds of acute dengue co-infection were recorded due to malaria in contrast to dengue mono-infection.ConclusionThis study showed a high prevalence of concurrent malaria and dengue fever in Africa. Healthcare workers should bear in mind the possibility of dengue infection as differential diagnoses for acute febrile illness as well as the possibility of co-existent malaria and dengue in endemic areas. Also, high-quality multi-centre studies are required to verify the above conclusions.Protocol registration number: CRD42022311301.
Clearing the Fog: A Systematic Review on Cognitive Dysfunction in COVID-19
Authors: Butardo Nicole D. , Coronel Mikaela Frances D. , Dino Alanna Marie O. , Mendoza Tiffany Ritz F. , Sto. Domingo Oliver Kyle DC. , Regencia Zypher Jude G. , Dominguez Jacqueline C. , Baja Emmanuel S. , Ligsay Antonio D. 
Published: May 2022

ABSTRACTObjectiveThe systematic review aims to examine the association between COVID-19 and cognitive dysfunction, including the link between the severity of COVID-19 and the occurrence of cognitive impairment and the potential pathophysiological mechanisms related to brain fog among COVID-19 patients.MethodsPubMed, Oxford University Press, ProQuest Health and Medical Complete, ScienceDirect, Ovid, HERDIN, Google Scholar, and Cochrane Library databases were accessed to retrieve literature using the PRISMA guidelines.ResultsAfter critical appraisal, thirteen full journal articles were included in the study. The studies showed the most frequent cognitive impairment are attention, memory, and executive function in COVID-19 patients. Compared with healthy controls (HC) in 3 out of 4 studies, cognitive impairment was only evident in COVID-19 patients. Furthermore, two studies showed no correlation between brain fog and depression, and five studies showed a link between the severity of COVID-19 infection and cognitive impairment. Cases ranging from mild to severe illness presented manifestations of brain fog. However, a disparity in the evidence of the pathophysiology of COVID-19 and cognitive dysfunction exists, prompting the need to investigate further. Additionally, recent studies provide insufficient evidence for direct central nervous system invasion, and there are emerging studies that contrast the presumed pathogenesis of neurological complications from neuroinflammation.ConclusionThere is an association between COVID-19 and cognitive dysfunction. Manifestation of cognitive dysfunction is present regardless of illness severity. Moreover, there are existing pathophysiological mechanisms of the Coronavirus that lead to cognitive dysfunction in COVID-19 patients; however, additional studies are required to substantiate such mechanisms further.PROSPERO Registration NumberCRD42022325669
Toward more realistic social distancing policies via advanced feedback control
Authors: Join Cédric , d’Onofrio Alberto , Fliess Michel 
Published: May 2022

AbstractA continuously time-varying transmission rate is suggested by many control-theoretic investigations on non-pharmaceutical interventions for mitigating the COVID-19 pandemic. However, such a continuously varying rate is impossible to implement in any human society. Here, we significantly extend a preliminary work (M. Fliess, C. Join, A. d’Onofrio, Feedback control of social distancing for COVID-19 via elementary formulae, MATHMOD, Vienna, 2022), based on the combination of flatness-based and model-free controls of the classic SIR model. Indeed, to take into account severe uncertainties and perturbations, we propose a feedback control where the transmission rate,i.e., the control variable, is piecewise constant. More precisely, the transmission rate remains constant during an appreciable time interval. Strict extended lockdowns may therefore be avoided. The poor knowledge of fundamental quantities such as the rate of infection hinders a precise calibration of the transmission rate. Thus, the results of our approach ought therefore not to be regarded as rules of action to follow accurately but as a guideline for a wise behavior.
Flexible use of contact calls in a species with high fission-fusion dynamics
Authors: Margarita Briseño-Jaramillo , Roberto Sosa-López José , Gabriel Ramos-Fernández , Alban Lemasson 
Published: May 2022

ABSTRACTThe ‘social complexity hypothesis’ posits that complex social systems (that entail high uncertainty) require complex communicative systems (with high vocal flexibility). In species with fission-fusion dynamics, where the fluid composition of temporary subgroups increases the uncertainty with which group members must manage their social relationships, vocal communication must be particularly flexible. This study assessed whether contact call rates vary with caller and audience characteristics in free-living spider monkeys, as well as with fission and fusion events. Adult females and immature individuals called more when in small audience settings, while audience size did not influence adult males. Adults called more when in the presence of the opposite sex, whereas immatures vocalized more in subgroups composed only by females. Females also called more when with their mature sons. We found higher call rates in periods during which fission and fusion events took place than in periods with more stable compositions and when the composition after a fission or fusion event changed from one sex to two sexes. A flexible use of contact calls allows individuals to identify themselves when they join others, particularly if they are members of the opposite sex. This socio-spatial cohesion function reduces the uncertainty about subgroup composition.
Handedness is associated with less common input to spinal motor neurons innervating different hand muscles
Authors: Maillet Jean , Avrillon Simon , Nordez Antoine , Rossi Jeremy , Hug François 
Published: May 2022

AbstractWhether the neural control of manual behaviours differs between the dominant and non-dominant hand is poorly understood. This study aimed to determine whether the level of common synaptic input to motor neurons innervating the same or different muscles differs between the dominant and the non-dominant hand. Seventeen participants performed two motor tasks with distinct mechanical requirements: an isometric pinch and an isometric rotation of a pinched dial. Each task was performed at 30% of maximum effort and was repeated with the dominant and non-dominant hand. Motor units were identified from two intrinsic (flexor digitorum interosseous and thenar) and one extrinsic muscle (flexor digitorum superficialis) from high-density surface electromyography recordings. Two complementary approaches were used to estimate common synaptic inputs. First, we calculated the coherence between groups of motor neurons from the same and from different muscles. Then, we estimated the common input for all pairs of motor neurons by correlating the low-frequency oscillations of their discharge rate. Both analyses led to the same conclusion, indicating less common synaptic input between motor neurons innervating different muscles in the dominant hand than in the non-dominant hand, which was only observed during the isometric rotation task. No differences in common input were observed between motor neurons of the same muscle. This lower level of common input could confer higher flexibility in the recruitment of motor units, and therefore, in mechanical outputs. Whether this difference between the dominant and non-dominant arm is the cause or the consequence of handedness remains to be determined.Key points-How the neural control of manual behaviours differs between the dominant and non-dominant hand remains poorly understood.-We decoded the spiking activities of spinal motor neurons innervating one extrinsic and two intrinsic hand muscles during isometric tasks.-We estimated the common synaptic input to motor neurons innervating the same or different muscles.-There is less common synaptic input between motor neurons innervating different muscles in the dominant than in the non-dominant hand during isometric rotation tasks.-No differences in common input were observed between motor neurons of the same muscle.-Lower level of common input could confer higher flexibility in the recruitment of motor units.