bluuebunny/crossref_metadata_2025 huggingface dataset:
Dyella humicola sp. nov., Dyella subtropica sp. nov., Dyella silvatica sp. nov. and Dyella silvae sp. nov., isolated from subtropical forest soil
Authors: Feng Guang-Da , Deng Xiaoqin , Li Jiali , Chen Wendi , Zhang Xianjiao , Zhu Honghui
Published: May 2023

Four novel bacterial strains, designated RBB1W86T, RXD159T, RBB189T and RLT163T, were isolated from subtropical forest soil of the Nanling National Nature Reserve located in Guangdong Province, PR China. 16S rRNA gene phylogeny indicated their affiliation to the genus

Dyella

, among which strains RBB1W86T and RXD159T were closely related to

Dyella halodurans

CGMCC 1.15435T with 16S rRNA gene sequence similarities of 98.8 and 99.5 %, respectively, and strains RBB189T and RLT163T were closely related to

Dyella tabacisoli

CGMCC 1.16273T (98.8 %) and

Dyella japonica

JCM 21530T (99.4 %), respectively. Phylogenomic analysis based on 92 core genes showed consistent phylogeny with the 16S rRNA gene phylogeny for strains RBB1W86T, RBB189T and RLT163T, while strain RXD159T showed a closer relationship with

D. tabacisoli

CGMCC 1.16273T and strain RBB189T. The genome-derived average nucleotide identity (ANI) values between the newly isolated strains and their closely related species were 70.18‒90.20 %, and the corresponding digital DNA–DNA hybridization (dDDH) values were 20.80‒40.30 %. Meanwhile, the ANI and dDDH values between each pair of the newly isolated strains were 75.80‒79.77 % and 21.30‒23.30 %, respectively. They all took iso-C15 : 0 and summed feature 9 (10-methyl C16  : 0 and/or iso-C17  : 1
ω9c) as the major fatty acids. Moreover, C16 : 0, iso-C16 : 0, iso-C17 : 0 and summed feature 3 (C16 : 1
ω7c and/or C16 : 1
ω6c) were also variously distributed as major components. They all took ubiquinone 8 as the only predominant respiratory quinone and phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine and an unidentified phospholipid as the major polar lipids. Phosphatidylmethylethanolamine was only present in strain RBB189T as another major component. Based on the results of phenotypic, genotypic and chemotaxonomic analyses, the newly isolated strains could be clearly distinguished from their closely related species and should represent four distinct novel species of the genus

Dyella

, for which the names Dyella humicola sp. nov. (type strain RBB1W86T=GDMCC 1.1901T=KACC 21988T), Dyella subtropica sp. nov. (type strain RXD159T=GDMCC 1.1902T=KACC 21989T), Dyella silvatica sp. nov. (type strain RBB189T=GDMCC 1.1900T=KACC 21990 T) and Dyella silvae sp. nov. (type strain RLT163T=GDMCC 1.1916T=KACC 21991T) are proposed.
Dehalogenimonas etheniformans sp. nov., a formate-oxidizing, organohalide-respiring bacterium isolated from grape pomace
Authors: Cui Yiru , Li Xiuying , Yan Jun , Lv Yan , Jin Huijuan , Wang Jingjing , Chen Gao , Kara-Murdoch Fadime , Yang Yi , Löffler Frank E.
Published: May 2023

A strictly anaerobic, organohalide-respiring bacterium, designated strain GPT, was characterized using a polyphasic approach. GPT is Gram-stain-negative, non-spore-forming and non-motile. Cells are irregular cocci ranging between 0.6 and 0.9 µm in diameter. GPT couples growth with the reductive dechlorination of 1,2-dichloroethane, vinyl chloride and all polychlorinated ethenes, except tetrachloroethene, yielding ethene and inorganic chloride as dechlorination end products. H2 and formate serve as electron donors for organohalide respiration in the presence of acetate as carbon source. Major cellular fatty acids include C16 : 0, C18 : 1ω9c, C16 : 1, C14 : 0 and C18 : 0. On the basis of 16S rRNA gene phylogeny, GPT is most closely related to

Dehalogenimonas formicexedens

NSZ-14T and

Dehalogenimonas alkenigignens

IP3-3T with 99.8 and 97.4 % sequence identities, respectively. Genome-wide pairwise comparisons based on average nucleotide identity, average amino acid identity and digital DNA–DNA hybridization do not support the inclusion of GPT in previously described species of the genus

Dehalogenimonas

with validly published names. On the basis of phylogenetic, physiological and phenotypic traits, GPT represents a novel species within the genus

Dehalogenimonas

, for which the name

Dehalogenimonas etheniformans

sp. nov. is proposed. The type strain is GPT (= JCM 39172T = CGMCC 1.17861T).
Independent origins and evolution of the secondary replicons of the class Gammaproteobacteria
Authors: Riccardi Christopher , Koper Piotr , Innocenti Gabriel , diCenzo George C. , Fondi Marco , Mengoni Alessio , Perrin Elena
Published: May 2023

Multipartite genomes, consisting of more than one replicon, have been found in approximately 10 % of bacteria, many of which belong to the phylum Proteobacteria. Many aspects of their origin and evolution, and the possible advantages related to this type of genome structure, remain to be elucidated. Here, we performed a systematic analysis of the presence and distribution of multipartite genomes in the class Gammaproteobacteria, which includes several genera with diverse lifestyles. Within this class, multipartite genomes are mainly found in the order Alteromonadales (mostly in the genus

Pseudoalteromonas

) and in the family

Vibrionaceae

. Our data suggest that the emergence of secondary replicons in Gammaproteobacteria is rare and that they derive from plasmids. Despite their multiple origins, we highlighted the presence of evolutionary trends such as the inverse proportionality of the genome to chromosome size ratio, which appears to be a general feature of bacteria with multipartite genomes irrespective of taxonomic group. We also highlighted some functional trends. The core gene set of the secondary replicons is extremely small, probably limited to essential genes or genes that favour their maintenance in the genome, while the other genes are less conserved. This hypothesis agrees with the idea that the primary advantage of secondary replicons could be to facilitate gene acquisition through horizontal gene transfer, resulting in replicons enriched in genes associated with adaptation to different ecological niches. Indeed, secondary replicons are enriched both in genes that could promote adaptation to harsh environments, such as those involved in antibiotic, biocide and metal resistance, and in functional categories related to the exploitation of environmental resources (e.g. carbohydrates), which can complement chromosomal functions.
INFLUENCE OF AVAILABILITY, BARRIERS TO ACCESSIBILITY, AND UTILIZATION OF MENTAL HEALTH SERVICES ON PSYCHOLOGICAL DISTRESS STATUS OF UNDERGRADUATE STUDENTS AT UNITED STATES INTERNATIONAL UNIVERSITY-AFRICA, KENYA
Authors: Wao Melvin A. , Omolo Calvin A. , Some Eliab , Kihara Michael , Njoroge Gladys
Published: May 2023

Background

Psychological distress is prevalent among university students worldwide. Research shows that there are inadequate efforts being made to improve the mental health of university students and there is low level of accessibility of university students to mental health services. This study aimed to determine the relationship between availability of mental health services, barriers to access to the services, and utilization of the services, on psychological distress status of undergraduate students at United States International University-Africa, Kenya

Methods

The research was conducted using a mixed methods research approach. Specifically, an exploratory sequential mixed methods research design was employed, including a cross-sectional survey and key informant interviews. The sample population was 249 undergraduate students at USIU-A, collected using cluster and stratified sampling procedure. Kessler Psychological Distress Scale (K10) was used to determine psychological distress status.

Results

This study found 76.8% of undergraduate students suffer from psychological distress with highest prevalence among seniors. Majority of students were aware of available sources of mental health services with three most frequently cited sources by students including counselor (87%), social support (84%), and peer counselor (80%). It was found that psychological distress status varies by students’ awareness of availability of psychologists or personal coping strategist. Association between barriers of accessibility and utilization of mental health services to psychological distress status of students i.e., peer stigma, societal stigma, and self-sufficiency.

Conclusion

At USIU-A, majority of students suffer from psychological distress. Whereas several sources of mental health services are available at the institution, a good number prefer to seek informal mental health services and two major barriers to mental health service accessibility include attitudinal barriers and stigma.

GRAPHICAL ABSTRACT
Natural Language Processing Techniques to Identify Zoonosis Awareness
Authors: Gonzalez Roger Geertz
Published: May 2023

In this study, we incorporated several NLP techniques to identify the most important factors in the open-ended responses part of theKnowledge, Attitudes, and Practices: Survey of Zoonoses in Wildlife Trade (KAP)in Cambodia. These included: TF-IDF, ngrams, Latent Semantic allocation (LSA), k-means, Latent Dirichlet Allocation (LDA), and Top2Vec. The top topics participants identified included 1) stating that they handled wildlife by setting traps and mist nets, 2) stating they were bitten by bat or rat, 3) which zoonotic symptoms caused sickness, 4) describing how they would go to the hospital when they came down with zoonotic symptoms, and 5) saying that they were aware of avian flu and its symptoms.

Based on our findings, recommendations for Cambodian public health officials include: 1) they need to educate participants to wear protective gear to prevent from being bitten by bats and rats during their jobs with these animals, and 2) they need to educate participants about the danger of different types of zoonotic diseases including Ebolavirus, Mojianvirus, etc., so that these participants can recognize the risks when handling bats and rats, and so they can take early action by seeking medical help as soon as they are bitten.
Association between social networks and substance use among male tribal adolescents in the North-East Indian state of Tripura
Authors: Debbarma Benjamin , Srivastava Ankita , Saikia Nandita
Published: May 2023

Abstracts

Purpose

The prevalence of substance use among tribal adolescents in north-east India is higher than that of the rest of India.

Objective

The study aimed to investigate the association between social network measures and substance use among male tribal adolescents in the West district of Tripura, North-East India.

Methods

We used data on 12-19-year-old tribal adolescents (N=340) from a primary cross-sectional survey in selected schools in the study area. We carried out bivariate and logistic regression analysis to establish the association between substance use and social network.

Results

Out of the total sample 340, about 27.65% reported smoking, 26.18% reported using smokeless tobacco, and 30.59% reported drinking alcohol; 35.29% reported using any of these substances. The substance use status of social network members was highly correlated to the substance use status among adolescents. The odds of substance consumption among adolescents increase with having a friend who smokes (OR = 6.152, 95% CI = 1.80–21.09), having friends who instigate to smoke (OR = 5.41, 95% CI = 1.86–15.74), and having friends who say smoking as a sign of masculinity(OR = 5.19, 95% CI = 1.4–18.22). Adolescents were more likely to smoke when their family member uses a substance (OR = 3.39, 95% CI = 1.5– 7.4,p= 0.002) and who spent time with friends with the same behaviour (OR = 2.66, 95% CI= 1.5–4.5,p≤ 0.000).

Conclusions

Intervention is needed to address adolescents’ substance use habits and members belonging to close social networks.
Intermittent Theta Burst Stimulation (iTBS) and Resting State Functional Connectivity in People Living with HIV/AIDS (PLWHA) Who Smoke Tobacco Cigarettes
Authors: Rakesh Gopalkumar , Adams Thomas G. , Morey Rajendra A. , Alcorn Joseph L. , Khanal Rebika , Su Amanda E. , Himelhoch Seth S. , Rush Craig R.
Published: May 2023

Background

People living with HIV (PLWHA) smoke at three times the rate of the general population and respond poorly to cessation strategies. Previous studies examined transcranial magnetic stimulation (TMS) over left dorsolateral prefrontal cortex (L. dlPFC) to reduce craving, but no studies have explored TMS among PLWHA who smoke. The current pilot study compared the effects of active and sham intermittent theta-burst stimulation (iTBS) on resting state functional connectivity (rsFC), cigarette cue attentional bias, and cigarette craving in PLWHA who smoke.

Methods

Eight PLWHA were recruited (single-blind, within-subject design) to receive one session of iTBS (n=8) over the L. dlPFC using neuronavigation and, four weeks later, sham iTBS (n=5). Cigarette craving and attentional bias assessments were completed before and after both iTBS and sham iTBS. rsFC was assessed before iTBS (baseline) and after iTBS and sham iTBS.

Results

Compared to sham iTBS, iTBS enhanced rsFC between the L. dlPFC and bilateral medial prefrontal cortex and pons. iTBS also enhanced rsFC between the right insula and right occipital cortex compared to sham iTBS. iTBS also decreased cigarette craving and cigarette cue attentional bias.

Conclusion

iTBS could potentially offer a therapeutic option for smoking cessation in PLWHA.
Malaria Infection in Patients with Sickle Cell Disease in Nigeria: Association with Markers of Hyposplenism
Authors: Ladu Adama I , Kadaura Mairo Y , Dauda Mohammed , Baba Abubakar Sadiq , Zango Nasir Garba , Jeffery Caroline , Farate Abubakar , Adekile Adekunle , Bates Imelda
Published: May 2023

Background

Malaria is considered an important cause of morbidity and mortality among people living with sickle cell disease (SCD). This has partly been attributed to the loss of splenic function that occurs early in the disease process. We aimed to study the prevalence of malaria infection among Nigerian SCD patients and explore the association with spleen size and function.

Method

This was a hospital-based, cross-sectional study performed at the University of Maiduguri Teaching Hospital in North-Eastern Nigeria from October 2020 to November 2021. Giemsa-stained blood smears for malaria parasites, Howell-Jolly body (HJB) red cells enumeration for spleen function evaluation and ultrasonography for spleen size assessment, were performed in acutely-ill SCD patients. Results of malaria parasitaemia and parasite density were compared with those of steady-state SCD patients and non-SCD controls.

Results

A total of 394 participants consisting of 119 acutely-ill SCD patients, 167 steady-state SCD controls and 108 non-SCD controls were studied. The prevalence ofP. falciparumparasitaemia was 51.3% in acutely-ill SCD patients, 31.7% in steady-state SCD controls and 13.0% in the non-SCD controls. In the SCD group, the mean parasite density was significantly higher among the acutely-ill SCD patients than the steady-state SCD controls (29,747 vs 18,563 parasites / ul;P = 0.001). Although parasitaemia prevalence was lower among the non-SCD controls, parasite density was significantly higher compared to both SCD groups (P = 0.0001). Among the acutely-ill SCD patients, the prevalence of clinical malaria and severe malaria anaemia were highest among children less than 5 years of age. Prevalence of parasitaemia (P = 0.540) and parasite density (P = 0.975) among acutely-ill SCD patients with visualized spleens on ultrasonography were not statistically different compared to those with absent spleens. Similarly, the frequency of HJB red cells among patients with parasitaemia was not significantly different compared to patients without parasitaemia (P = 0.183).

Conclusion

Our study highlights the frequency and role of malaria infection in acutely-ill SCD patients, especially in those younger than five years. Although we have found no evidence of an increased risk of malaria parasitaemia or parasite density with markers of hyposplenism, the role played by an underlying immunity to malaria among SCD patients is not clear. Further studies are required to elucidate the role of hyposplenism and malaria in SCD patients in malaria-endemic regions.
Higher Family Income and Clinical Dental Outcomes of Minority Children: A Cross-Sectional Study
Authors: Okuji David , Luo Rolina , Wei Tianqi , Lee Myeonggyun
Published: May 2023

Purpose

This study utilized Minorities’ Diminished Return theory and aimed to learn if minority children gain less protective effect from higher family income compared to White children for dental caries and multiple oral health problems.

Methods

This study was designed cross-sectionally from 21,599 subject-responses to the 2017 National Survey of Children’s Health. Specific outcomes included parental-reported dental caries and multiple oral health problems (e.g., toothaches, bleeding gums, and/or caries) compared across Hispanic and non-Hispanic White, Black, Asian, and Multi-race children. Logistic regression models estimated the effects of race/ethnicity on each outcome, with adjustments for child sex, parental education, child age, and income-to-needs ratio.

Results

The findings showed when all racial/ethnic groups increased family income and socioeconomic status, there were no statistically significant differences between all racial/ethnic groups for the parental-reported dental caries and multiple oral health problems.

Conclusions

This study’s findings show either 1) Minorities’ Diminished Return theory, which postulates that structural racism negatively impacts health gains from higher socioeconomic status for minority children, does not apply to children’s dental caries and multiple oral health problems or 2) the biologic load of the caries disease process supersedes the protective health gain effects from increased family income, expected by Minorities’ Diminished Return theory. Regardless, dentists and policymakers must support best practices and policies which benefit entire populations of children, through widespread disease prevention techniques, access-to-care, and utilization-of-care programs to decrease levels of childhood caries and other oral health problems.
Carboxypeptidase B2 gene polymorphisms in the donor associate with kidney allograft loss
Authors: Poppelaars Felix , Eskandari Siawosh K. , Damman Jeffrey , Frazer-Abel Ashley , Holers V. Michael , Dixon Bradley P. , Daha Mohamed R. , Sanders Jan-Stephan F. , Seelen Marc A. , Faria Bernardo , Costa Mariana Gaya da , Thurman Joshua M.
Published: May 2023

Introduction

Plasma carboxypeptidase B2 (CPB2) is an enzyme that cleaves C-terminal amino acids from proteins, thereby regulating their activities. CPB2 has anti-inflammatory and anti-fibrinolytic properties and can therefore be protective or harmful in disease. We explored the impact of functional carboxypeptidase B2 gene (CPB2) polymorphisms on graft survival following kidney transplantation.

Methods

We performed a longitudinal cohort study to evaluate the association of functionalCPB2polymorphisms (rs2146881, rs3742264, rs1926447, rs3818477) and complement polymorphisms (rs2230199, rs17611) with long-term allograft survival in 1,271 kidney transplant pairs from the University Medical Center Groningen in The Netherlands.

Results

The high-producingCPB2rs3742264 polymorphism in the donor was associated with a reduced risk of graft loss following kidney transplantation (hazard ratio, 0.71 for the A-allele; 95%-CI, 0.55–0.93;P=0.014). In fully adjusted models, the association between the CPB2 polymorphism in the donor and graft loss remained significant. The protective effect of the high-producingCPB2variant in the donor could be mitigated by the hazardous effect of gain-of-function complement polymorphisms. Additionally, we compiled a genetic risk score of the fourCPB2variants in the recipients and donors, which was independently associated with long-term allograft survival. Furthermore, this genetic risk score substantially improved risk prediction for graft loss beyond currently used clinical predictors.

Conclusion

Kidney allografts from deceased donors possessing a high-producing CPB2 polymorphism are at a lower risk of graft loss after kidney transplantation. Furthermore, our findings suggest that CPB2 might have a protective effect on graft loss through its ability to inactivate complement anaphylatoxins.

Essentials

Carboxypeptidase B2 (CPB2) is a metalloprotease with anti-fibrinolytic and anti-inflammatory properties.

We investigated the impact ofCPB2polymorphisms on graft loss after kidney transplantation.

The rs3742264-A SNP in the donor, linked to higher CPB2 levels, decreased the risk of graft loss.

CPB2 could have a protective effect on graft survival by inactivating complement anaphylatoxins.
Quantification of joint mobility limitation in adult type 1 diabetes
Authors: Phatak Sanat , Mahadevkar Pranav , Chaudhari Kaustubh , Chakladar Shreya , Jain Swasti , Dhadge Smita , Jadhav Sarita , Wagh Rucha , Shah Rohan , Bhalerao Aboli , Patil Anupama , Ingram Jennifer , Goel Pranay , Yajnik Chittaranjan
Published: May 2023

Background

Diabetic cheiroarthropathies consist of limited joint mobility (LJM), flexor tenosynovitis (FTS), Dupuytren’s contracture (DC), and carpal tunnel syndrome (CTS). There is heterogeneity in definitions and lack of a method to measure hand fibrosis load. We measured metacarpophalangeal (MCP) joint restriction and describe magnetic resonance (MR) imaging characteristics across the spectrum of joint restriction.

Methods

Adults with type 1 diabetes were screened for hand manifestations using a symptom questionnaire, clinical examination, function (Duruoz hand index (DHI), grip strength). We measured maximum possible extension at the MCP joint. Patients were segregated by mean MCP extension (<20 degrees, 20-40 degrees, 40-60 degrees, and >60 degrees) for MRI scanning. Patients in the four groups were compared using ANOVA for clinical features as well as MRI measurements (tenosynovial, skin, and fascia thickness, additive score of three).

Findings

Of 237 patients (90 males), 79 (33.8%) had cheiroarthropathy; these had MCP extension limitation (39 degrees versus 61 degrees, p<0.01). Groups with restricted MCP extension were older, had higher prevalence of retinopathy and nephropathy, and higher DHI (1.9 vs 0.2) but very few (7%) had pain. MRI scans of the hand (n=61) showed flexor tenosynovitis in four and median neuritis in one. Groups with maximum MCP limitation had the thickest palmar skin but mean tendon thickness or median nerve area did not differ. The additive score could differentiate between levels of joint mobility restriction. Only mean palmar skin thickness was associated with MCP extension angle in multiple linear regression.

Interpretation

Joint mobility limitation, quantified by restricted MCP extension, was driven by skin thickening. MCP extension and fibrosis scoring on MRI can serve as quantitative measures of hand involvement for future associative studies.
“Now you see me”: detecting asymptomatic infectious individuals in the population
Authors: Iseli Alena , Dobay Akos , Breitling Lutz Philipp
Published: May 2023

Quarantine is an effective countermeasure to stop or slow the spread of an emerging infectious disease when no other preventive measures are available to protect the population. However, when the disease results in a proportion of asymptomatic infections, the spread dynamics are affected, and quarantine efficiency is impaired.

Here, we introduce an extended susceptible-infected-recovered (SIR) model to study the effects of asymptomatic individuals at the onset of an emerging infectious disease when no vaccination is yet available and/or when a vaccine is available but only a subset of the population can be vaccinated due to limited supply or the unwillingness of susceptible individuals to receive an injection. These aspects have been indirectly incorporated into the model using a time-dependent vaccination rate.

With this model, we confirm that, in the case of a missing vaccine, quarantine is effective in stopping the spread of an infectious disease, but its efficiency can be substantially reduced in the presence of individuals developing asymptomatic infection. Moreover, we show that vaccination is effective only if available early during the epidemic and if the vaccination rate is sufficiently high. By applying this model to Zurich and all of Switzerland in case of the COVID-19 pandemic, we found that the following two strategies have similar outcomes: either placing infectious individuals into quarantine when no vaccine is available or dropping quarantine measures but administering a vaccine at a daily rate of 1%, starting no later than 105 days after the onset of the epidemic. Beyond this time period, a vaccination campaign will have no effect in stopping the spread of the disease if 25% of the susceptible population is asymptomatic. We also found that the option of deploying a vaccination campaign was more effective for all of Switzerland than for only the city of Zurich.
Real-world study of Cerviron®vaginal ovules in the treatment of cervical lesions of various etiologies
Authors: Petre Izabella , Sirbu Daniela Teodora , Petrita Ramona , Toma Andreea-Denisa , Peta Ema , Dimcevici-Poesina Florentina
Published: May 2023

Cervical lesions can be caused by pathogens, hormonal changes or by cervical injury. The recommended treatment in all cases is excision. Local re-epithelialization therapy should be initiated preoperatively and postoperatively. The present study assessed the post-market performance and tolerability of Cerviron®ovules in the treatment and management of cervical lesions postoperatively. The study population included 345 participants aged 20-70 years with either a cervical lesion under treatment or with recent surgical removal of a cervical lesion. The degree of re-epithelialization of the cervical mucosa was improved in 73.17% of the patients evaluated during routine colposcopy exams and 92.73% of patients recorded no bleeding. When adding Cerviron®either as monotherapy or in association with other antimicrobials in postoperative care of the cervical ectropion, improved postoperative outcomes such as reduced post-interventional bleeding and a superior quality of healing were observed. The study and its details are registered inwww.clinicaltrials.govunder IDNCT05668806.
Insight into risk associated phenotypes behind COVID-19 from phenotype genome-wide association studies
Authors: Chen Zhongzhong , Matsuda Koichi
Published: May 2023

Long COVID presents a complex and multi-systemic disease that poses a significant global public health challenge. Symptoms can vary widely, ranging from asymptomatic to severe, making the condition challenging to diagnose and manage effectively. Furthermore, identifying appropriate phenotypes in genome-wide association studies of COVID-19 remains unresolved. This study aimed to address these challenges by analyzing 220 deep-phenotype genome-wide association data sets (159 diseases, 38 biomarkers and 23 medication usage) from BioBank Japan (BBJ) (n=179,000), UK Biobank and FinnGen (n=628,000) to investigate pleiotropic effects of known COVID-19 risk associated single nucleotide variants. Our findings reveal 32 different phenotypes that share the common genetic risk factors with COVID-19 (p< 7.6×10−11), including two diseases (myocardial infarction and type 2 diabetes), 26 biomarkers with seven categories (blood cell, metabolic, liver-related, kidney-related, protein, inflammatory and anthropometric), and four medications (antithrombotic agents, HMG CoA reductase inhibitors, thyroid preparations and anilides). As long COVID continues to coexist with humans, our results highlight the need for targeted screening to support specific vulnerable populations to improve disease prevention and healthcare delivery.
An algorithm for automated detection of evoked potentials from polarity reversed electrical stimulations
Authors: Vidmark Jessica S L , Sanger Terence D
Published: May 2023

Background

In neurophysiological research involving neural responses to electrical stimuli, each recording must be searched for evoked potentials (EPs) prior to further analysis. Conducting this process manually is time consuming for the researcher and also inserts bias. However, automated detection methods often struggle to distinguish between artifacts and neural responses, which can have highly complex and varying shapes.

Methods

We have developed a novel algorithm for automated detection of polarity reversed EPs (ADPREP), which uses the knowledge that reversing the polarity of a pair of stimulating contacts reverses the sign of the stimulus artifact, but not that of the neural response. Hence, our algorithm searches for any positive correlation between the recordings from two polarity reversed stimulations, after removing any stimulus decay artifacts. If the peak-to-peak amplitude in a positively correlated region surpasses a user-defined threshold, the recording is labeled as an EP; otherwise, it is not. Neural recordings from deep brain nuclei and cortical regions during deep brain stimulation (DBS) in 28 pediatric patients with dystonia were used to test and prove the validity of the method.

Results

The ADPREP algorithm is able to distinguish EPs of varying shapes and sizes with a high level of accuracy, as early as 0.35 ms after stimulation, despite large stimulus artifacts. The algorithm has proven useful in initial tests with DBS data in hundreds of stimulation/recording combinations within the basal ganglia and thalamic nuclei as well as from these deep brain nuclei to cortex, at stimulation frequencies up to 250 Hz.

Conclusion

Our automated EP detection algorithm can accurately detect DBS EPs in deep brain nuclei and cortex, and has promising applications in other stimulation and recording modalities that allow for polarity reversal of the recorded stimulus artifact. The algorithm successfully labels EPs of varying shapes and sizes, as early as a fraction of a millisecond after stimulation, in a range of stimulus frequencies and stimulation-recording pairs – even under large stimulus decay artifacts and in same-lead stimulation and recordings. As such, it is a great method to improve efficacy and minimize human bias, setting up for more reliable conclusions to be drawn from the data.
Rising daptomycin resistance inEnterococcus faeciumacross a hospital system occurred via rampant recurrent evolution and occasional transmission between patients
Authors: Woods Robert J. , Forstchen Meghan , Kinnear Clare , McKaig Jordan , Patel Twisha , Tracy Kevin , Young Carol , Read Andrew F.
Published: May 2023

The rise of antibiotic resistance in a population involves two distinct processes: the origin of resistance and its spread. Here we study the contribution of both processes to the increase in daptomycin resistance inEnterococcus faeciumin a hospital system. This case-control genomic study includes whole-genome sequencing of 82 isolates obtained from 24 case patients with clinically determined daptomycin-resistance and 24 controls. Among the case patients, the first isolate was resistant in 15 patients (R patients) while in the remaining nine the first isolate was susceptible but was followed by one or more resistant isolates (SR patients). Mutations in a set of candidate daptomycin resistance genes were compared within and between all patients. Additionally, among closely related isolates, mutations were identified across the entire assembled genome. Daptomycin resistance evolved separately multiple times and there was no phylogenetic clustering of the R or the SR groups. Six of the nine SR pairs gained mutations in previously identified candidate loci for daptomycin resistance, with the major cardiolipin synthase (clsA) being mutated most frequently. The hospital-wide increases in daptomycin resistance inE. faeciumwas the result of recurrent evolution taking multiple evolutionary pathways and occasional transmission of resistant isolates between patients.

Importance

Antimicrobial resistance in healthcare settings presents an important challenge, because infections with resistant organisms are associated with higher cost, longer hospital stays and worse outcomes for patients. However, it can be difficult to identify the factors driving the increase in resistance, specifically the relative contribution of resistance arising anew through mutation versus the transmission of resistant organisms from patient to patient. We study a hospital where resistance to daptomycin was increasing amongEnterococcus faecium, an important hospital pathogen. We find the increase in resistance was the results of resistance arising many times independently. We also identify occasional transmission of daptomycin resistant organisms. Thus, control of daptomycin resistance inE. faeciummay require interventions that both slow the emergence of resistance within patients and slow its spread. This work sheds light on the complex population dynamics leading to antibiotic resistance in hospitals.
Projecting the potential impact of an Omicron XBB.1.5 wave in Shanghai, China
Authors: Liu Hengcong , Xu Xiangyanyu , Deng Xiaowei , Hu Zexin , Sun Ruijia , Zou Junyi , Dong Jiayi , Wu Qianhui , Chen Xinhua , Yi Lan , Cai Jun , Zhang Juanjuan , Ajelli Marco , Yu Hongjie
Published: May 2023

China experienced a major nationwide wave of SARS-CoV-2 infections in December 2022, immediately after lifting strict interventions, despite the majority of the population having already received inactivated COVID-19 vaccines. Due to the rapid waning of protection and the emergence of Omicron XBB.1.5, the risk of another COVID-19 wave remains high. It is still unclear whether the health care system will be able to manage the demand during this potential XBB.1.5 wave and if the number of associated deaths can be reduced to a level comparable to that of seasonal influenza. Thus, we developed a mathematical model of XBB.1.5 transmission using Shanghai as a case study. We found that a potential XBB.1.5 wave is less likely to overwhelm the health care system and would result in a death toll comparable to that of seasonal influenza, albeit still larger, especially among elderly individuals. Our analyses show that a combination of vaccines and antiviral drugs can effectively mitigate an XBB.1.5 epidemic, with a projected number of deaths of 2.08 per 10,000 individuals.

This figure corresponds to a 70–80% decrease compared to the previous Omicron wave and is comparable to the level of seasonal influenza. The peak prevalence of hospital admissions and ICU admissions are projected at 28.89 and 2.28 per 10,000 individuals, respectively, suggesting the need for a moderate increase in the capacity of the health care system. Our findings emphasize the importance of improving vaccination coverage, particularly among the older population, and the use of antiviral treatments.
Ability to detect fake news predicts sub-national variation in COVID-19 vaccine uptake across the UK
Authors: Loomba Sahil , Maertens Rakoen , Roozenbeek Jon , Götz Friedrich M. , van der Linden Sander , de Figueiredo Alexandre
Published: May 2023

Susceptibility to believing false or misleading information is associated with a range of adverse outcomes. However, it is notoriously difficult to study the link between susceptibility to misinformation and consequential real-world behaviors such as vaccine uptake. In this preregistered study, we devise a large-scale socio-spatial model that combines the rigor of a psychometrically validated test of misinformation susceptibility administered to a nationally representative sample of 16,477 individuals with COVID-19 vaccine uptake data of 129 sub-national regions published by the United Kingdom (UK) government, to show that the general ability to detect misinformation strongly and positively predicts regional vaccine uptake in the UK. We put this practically significant correlational effect size into perspective by noting how psychological interventions that reduce individuals’ misinformation susceptibility could be associated with additional vaccine uptake.
Polygenic Risk Associated with Alzheimer’s Disease and Other Traits Influences Genes Involved in T Cell Signaling and Activation
Authors: Dressman Dallin , Tasaki Shinya , Yu Lei , Schneider Julie , Bennett David A. , Elyaman Wassim , Vardarajan Badri
Published: May 2023

T cells, members of the adaptive immune system known for their ability to respond to an enormous variety of pathogens and other insults, are increasingly recognized as important mediators of pathology in neurodegeneration and other diseases. Previously, we and others have shown that T cell gene expression phenotypes are regulated by genetic variants associated with autoimmune disease, neurodegenerative disease, and inflammatory processes. However, many complex diseases have polygenic risk with thousands of common variants contributing a small amount to disease heritability. Here, we compute the polygenic risk score (PRS) of several autoimmune, neurological, and psychiatric disorders and present the first correlation of these PRSs with T cell gene expression, using transcriptomic and genomic sequencing data from a cohort of Alzheimer’s disease (AD) patients and age-matched controls. We validate our AD PRS against clinical metrics in our cohort and then compare PRS-associated genes across traits and four T cell subtypes. Several genes and biological pathways associated with the PRS for these traits relate to functions such as T cell chemotaxis, differentiation, response to and production of cytokines, and regulation of T cell receptor signaling. We also found that the trait-associated gene expression signature for certain traits was polarized towards a particular T cell subset, such as CD4+ for autoimmune disease traits or CD8+ for some psychiatric disease traits. Our findings may help guide efforts in precision medicine to target specific T cell functions in individuals with high polygenic risk for various complex diseases.
Custom-engineered hydrogels for delivery of human iPSC-derived neurons into the injured cervical spinal cord
Authors: Doulames V.M. , Marquardt L.M. , Hefferon M.E. , Baugh N. , Suhar R.A. , Wang A.T. , Dubbin K. , Weimann J.M. , Palmer T.D. , Plant G.W. , Heilshorn S.C.
Published: May 2023

Cervical damage is the most prevalent type of spinal cord injury clinically, although few preclinical research studies focus on this anatomical region of injury. Here we present a combinatorial therapy composed of a custom-engineered, injectable hydrogel and human induced pluripotent stem cell (iPSC)-derived deep cortical neurons. The biomimetic hydrogel has a modular design that includes a protein-engineered component to allow customization of the cell-adhesive peptide sequence and a synthetic polymer component to allow customization of the gel mechanical properties.In vitrostudies with encapsulated iPSC-neurons were used to select a bespoke hydrogel formulation that maintains cell viability and promotes neurite extension. Following injection into the injured cervical spinal cord in a rat contusion model, the hydrogel biodegraded over six weeks without causing any adverse reaction. Compared to cell delivery using saline, the hydrogel significantly improved the reproducibility of cell transplantation and integration into the host tissue. Across three metrics of animal behavior, this combinatorial therapy significantly improved sensorimotor function by six weeks post transplantation. Taken together, these findings demonstrate that design of a combinatorial therapy that includes a gel customized for a specific fate-restricted cell type can induce regeneration in the injured cervical spinal cord.
An Interpretable Bayesian Clustering Approach with Feature Selection for Analyzing Spatially Resolved Transcriptomics Data
Authors: Li Huimin , Jiang Xi , Guo Lei , Xie Yang , Xu Lin , Li Qiwei
Published: May 2023

Summary

Recent breakthroughs in spatially resolved transcriptomics (SRT) technologies have enabled comprehensive molecular characterization at the spot or cellular level while preserving spatial information. Cells are the fundamental building blocks of tissues, organized into distinct yet connected components. Although many non-spatial and spatial clustering approaches have been used to partition the entire region into mutually exclusive spatial domains based on the SRT high-dimensional molecular profile, most require an ad-hoc selection of less interpretable dimensional-reduction techniques. To overcome this challenge, we propose a zero-inflated negative binomial mixture model to cluster spots or cells based on their molecular profiles. To increase interpretability, we employ a feature selection mechanism to provide a low-dimensional summary of the SRT molecular profile in terms of discriminating genes that shed light on the clustering result. We further incorporate the SRT geospatial profileviaa Markov random field prior. We demonstrate how this joint modeling strategy improves clustering accuracy, compared with alternative state-of-the-art approaches, through simulation studies and two real data applications.
Primary nasal viral infection rewires the tissue-scale memory response
Authors: Kazer Samuel W. , Match Colette Matysiak , Langan Erica M. , Messou Marie-Angèle , LaSalle Thomas J. , O’Leary Elise , Marbourg Jessica , Naughton Katherine , von Andrian Ulrich H. , Ordovas-Montanes Jose
Published: May 2023

The nasal mucosa is frequently the initial site of respiratory viral infection, replication, and transmission. Recent work has started to clarify the independent responses of epithelial, myeloid, and lymphoid cells to viral infection in the nasal mucosa, but their spatiotemporal coordination and relative contributions remain unclear. Furthermore, understanding whether and how primary infection shapes tissue-scale memory responses to secondary challenge is critical for the rational design of nasal-targeting therapeutics and vaccines. Here, we generated a single-cell RNA-sequencing (scRNA-seq) atlas of the murine nasal mucosa sampling three distinct regions before and during primary and secondary influenza infection. Primary infection was largely restricted to respiratory mucosa and induced stepwise changes in cell type, subset, and state composition over time. Type I Interferon (IFN)-responsive neutrophils appeared 2 days post infection (dpi) and preceded transient IFN-responsive/cycling epithelial cell responses 5 dpi, which coincided with broader antiviral monocyte and NK cell accumulation. By 8 dpi, monocyte-derived macrophages (MDMs) expressingCxcl9andCxcl16arose alongside effector cytotoxic CD8 andIfng-expressing CD4 T cells. Following viral clearance (14 dpi), rare, previously undescribedKrt13+nasalimmune-interactingfloorepithelial (KNIIFE) cells expressing multiple genes with immune communication potential increased concurrently with tissue-resident memory T (TRM)-like cells and early IgG+/IgA+ plasmablasts. Proportionality analysis coupled with cell-cell communication inference, alongside validation by in situ microscopy, underscored the CXCL16–CXCR6 signaling axis between MDMs and effector CD8 T cells 8dpi and KNIIFE cells and TRM cells 14 dpi. Secondary influenza challenge with a homologous or heterologous strain administered 60 dpi induced an accelerated and coordinated myeloid and lymphoid response without epithelial proliferation, illustrating how tissue-scale memory to natural infection engages both myeloid and lymphoid cells to reduce epithelial regenerative burden. Together, this atlas serves as a reference for viral infection in the upper respiratory tract and highlights the efficacy of local coordinated memory responses upon rechallenge.
Mitosis sets nuclear homeostasis of cancer cells under confinement
Authors: Mouelhi Malèke , Saffon Alexis , Roinard Morgane , Delanoë-Ayari Hélène , Monnier Sylvain , Rivière Charlotte
Published: May 2023

During their life, mammalian cells are subjected to numerous mechanical constraints, especially in pathological contexts such as cancer. Recent studies have highlighted the central role of the nucleus in sensing mechanical cues, but they only focus on short periods of time, and so far, whether cells can adapt to prolonged confinement remains unknown. Here, we reveal the unsuspected role of mitosis in the long-term adaptation of nuclei to prolonged uniaxial confinement. For the colorectal cancer cell line investigated, following the first confined cell division, a new homeostatic state was reached by nuclei: they were smaller, and had reset the tension of their envelope. This adaptation through mitosis relied both on the nuclear tension sensor cPLA2 and the contractility machinery. We report for the first time a mechano-adaptation during mitosis, a process that could be crucial to adapt to stresses in the tumor microenvironment. We therefore anticipate that our work could provide new insight into cancer cell plasticity and cancer relapse.

Significance Statement

Most cell types undergo significant deformation throughout their life cycles. Immune cells must deform to navigate through dense matrices, while cancer cells in solid tumors experience squeezing from neighboring cells. The nucleus, central for many cell function, is the stiffest and largest organelle. Understanding its long-term response to spatial constraints is hence crucial yet largely unexplored.

In this study, we investigate how a colorectal cancer cell line adapts to prolonged confined environments, with a particular focus on nuclear dynamics under continuous squeezing.

Our groundbreaking findings reveal for the first time a mechano-adaptation during mitosis leading to a decrease in nuclear size.

This research contributes to the fundamental understanding of cellular mechanosensing, opening new avenues for cancer biology research.
EVRC: Reconstruction of chromosome 3D structure models using Error-Vector Resultant algorithm with Clustering coefficient
Authors: Wang Xiao , Li Jie , Gu Wei-Cheng , Ma Bin-Guang
Published: May 2023

Reconstruction of 3D structure models is of great importance for the study of chromosome function. In this paper, we present a novel reconstruction algorithm, called EVRC, which utilizes co-clustering coefficients and error-vector resultant for chromosome 3D structure reconstruction. To evaluate the effectiveness and accuracy of the EVRC algorithm, we applied it to simulation datasets and real human Hi-C datasets. The results show that the reconstructed structures have high similarity to the original/real structures, indicating the effectiveness and robustness of the EVRC algorithm. Furthermore, we applied the algorithm to the 3D conformation reconstruction of the wild-type and mutantArabidopsis thalianachromosomes and demonstrated the differences in structural characteristics between different chromosomes. We also accurately showed the conformational change in the centromere region of the mutant compared with the wild-type ofArabidopsischromosome 1. Our EVRC algorithm is a valuable software tool for the field of chromatin structure reconstruction, and holds great promise for advancing our understanding on the chromosome functions.