bluuebunny/crossref_metadata_2025 huggingface dataset:
Light-driven biohybrid system utilizes N2 for photochemical CO2 reduction
Authors: Zeng Jin-Yue , Wang Xiao-Shuang , Liu Xin-Hua , Li Qian-Ru , Feng Jun , Zhang Xian-Zheng
Published: May 2023

Attempting to couple photochemical CO2 reduction with N2 fixation is usually difficult, because the reaction conditions for these two processes are typically incompatible. Here, we report that a light-driven biohybrid system can utilize abundant, atmospheric N2 to produce electron donors via biological nitrogen fixation, to achieve effective photochemical CO2 reduction. This biohybrid system is constructed by incorporating molecular cobalt-based photocatalysts into N2-fixing bacteria. It is found that N2-fixing bacteria can convert N2 into reductive organic nitrogen and create a localized anaerobic environment, which allows the incorporated photocatalysts to continuously perform photocatalytic CO2 reduction under aerobic conditions. Specifically, the light-driven biohybrid system displays a high formic acid production rate of over 1.41 × 10−14 mol h−1 cell−1 under visible light irradiation, and the organic nitrogen content undergoes an over-3-fold increase within 48 hours. This work offers a useful strategy for coupling CO2 conversion with N2 fixation under mild and environmentally benign conditions.
Efficient protein tagging and cis-regulatory element engineering via precise and directional oligonucleotide-based targeted insertion in plants
Authors: Kumar Jitesh , Char Si Nian , Weiss Trevor , Liu Hua , Liu Bo , Yang Bing , Zhang Feng
Published: May 2023

Efficient and precise targeted insertion holds great promise but remains challenging in plant genome editing. An efficient nonhomologous end-joining-mediated targeted insertion method was recently developed by combining clustered regularly interspaced short palindromic repeat (CRISPR)/Streptococcus pyogenes CRISPR-associated nuclease 9 (SpCas9) gene editing with phosphorothioate modified double-stranded oligodeoxynucleotides (dsODNs). Yet, this approach often leads to imprecise insertions with no control over the insertion direction. Here, we compared the influence of chemical protection of dsODNs on efficiency of targeted insertion. We observed that CRISPR/SpCas9 frequently induced staggered cleavages with 1-nucleotide 5′ overhangs; we also evaluated the effect of donor end structures on the direction and precision of targeted insertions. We demonstrate that chemically protected dsODNs with 1-nucleotide 5′ overhangs significantly improved the precision and direction control of target insertions in all tested CRISPR targeted sites. We applied this method to endogenous gene tagging in green foxtail (Setaria viridis) and engineering of cis-regulatory elements for disease resistance in rice (Oryza sativa). We directionally inserted 2 distinct transcription activator-like effector binding elements into the promoter region of a recessive rice bacterial blight resistance gene with up to 24.4% efficiency. The resulting rice lines harboring heritable insertions exhibited strong resistance to infection by the pathogen Xanthomonas oryzae pv. oryzae in an inducible and strain-specific manner.
Genetic background in the rat affects endocrine and metabolic outcomes of bisphenol F exposure
Authors: Wagner Valerie A , Holl Katie L , Clark Karen C , Reho John J , Dwinell Melinda R , Lehmler Hans-Joachim , Raff Hershel , Grobe Justin L , Kwitek Anne E
Published: May 2023

Environmental bisphenol compounds like bisphenol F (BPF) are endocrine-disrupting chemicals (EDCs) affecting adipose and classical endocrine systems. Genetic factors that influence EDC exposure outcomes are poorly understood and are unaccounted variables that may contribute to the large range of reported outcomes in the human population. We previously demonstrated that BPF exposure increased body growth and adiposity in male N/NIH heterogeneous stock (HS) rats, a genetically heterogeneous outbred population. We hypothesize that the founder strains of the HS rat exhibit EDC effects that were strain- and sex-dependent. Weanling littermate pairs of male and female ACI, BN, BUF, F344, M520, and WKY rats randomly received either vehicle (0.1% EtOH) or 1.125 mg BPF/l in 0.1% EtOH for 10 weeks in drinking water. Body weight and fluid intake were measured weekly, metabolic parameters were assessed, and blood and tissues were collected. BPF increased thyroid weight in ACI males, thymus and kidney weight in BUF females, adrenal weight in WKY males, and possibly increased pituitary weight in BN males. BUF females also developed a disruption in activity and metabolic rate with BPF exposure. These sex- and strain-specific exposure outcomes illustrate that HS rat founders possess diverse bisphenol-exposure risk alleles and suggest that BPF exposure may intensify inherent organ system dysfunction existing in the HS rat founders. We propose that the HS rat will be an invaluable model for dissecting gene EDC interactions on health.
Analysis and Evaluation of Intersectionality Theory for the Study of Access to Mental Health Services of Children With Refugee Background
Authors: Barbo Geneveave
Published: May 2023

Multiple and complex factors contribute to the health inequities faced by refugee children accessing mental health care. Nurses play a critical role in addressing health inequities through education, practice, policy, and research. Intersectionality theory holds the potential to support nursing research that seeks to critically examine intersecting social identities and power structures that impact health inequities experienced by refugee children with mental health difficulties. Using Fawcett's framework, this article examined intersectionality theory and its applicability to the topic of inquiry. The findings revealed that much work is still required for intersectionality theory to meet the criteria for theory evaluation.
Incidences and outcomes of intra-operative vs. postoperative paediatric cardiac arrest
Authors: Rattana-Arpa Sirirat , Chaikittisilpa Nophanan , Srikongrak Salalee , Udomnak Suphanithi , Aroonpruksakul Naiyana , Kiatchai Taniga
Published: May 2023

BACKGROUND

The reported incidence of paediatric perioperative cardiac arrest (PPOCA) in most developing countries ranges from 2.7 to 22.9 per 10 000 anaesthetics, resulting in mortality rates of 2.0 to 10.7 per 10 000 anaesthetics. The definitions of ‘peri-operative’ cardiac arrest often include the intra-operative period and extends from 60 min to 48 h after anaesthesia completion. However, the characteristics of cardiac arrests, care settings, and resuscitation quality may differ between intra-operative and early postoperative cardiac arrests.

OBJECTIVE

To compare the mortality rates between intraoperative and early postoperative cardiac arrests (<24 h) following anaesthesia for paediatric noncardiac surgery.

DESIGN

A retrospective cohort study.

SETTING

In a tertiary care centre in Thailand during 2014 to 2019, the peri-operative period was defined as from the beginning of anaesthesia care until 24 h after anaesthesia completion.

PATIENTS

Paediatric patients aged 0 to 17 years who underwent anaesthesia for noncardiac surgery.

MAIN OUTCOME MEASURES

Mortality rates.

RESULTS

A total of 42 776 anaesthetics were identified, with 63 PPOCAs and 23 deaths (36.5%). The incidence (95% confidence interval) of PPOCAs and mortality were 14.7 (11.5 to 18.8) and 5.4 (3.6 to 8.1) per 10 000 anaesthetics, respectively. Among 63 PPOCAs, 41 (65%) and 22 (35%) occurred during the intra-operative and postoperative periods, respectively. The median [min to max] time of postoperative cardiac arrest was 3.84 [0.05 to 19.47] h after anaesthesia completion. Mortalities (mortality rate) of postoperative cardiac arrest were significantly higher than that of intra-operative cardiac arrest at 14 (63.6%) vs. 9 (22.0%, P = 0.001). Multivariate analysis of risk factors for mortality included emergency status and duration of cardiopulmonary resuscitation with adjusted odds ratio 5.388 (95% confidence interval (1.031 to 28.160) and 1.067 (1.016 to 1.120).

CONCLUSIONS

Postoperative cardiac arrest resulted in a higher mortality rate than intra-operative cardiac arrest. A high level of care should be provided for at least 24 h after the completion of anaesthesia.

TRIAL REGISTRATION

None.

CLINICAL TRIAL NUMBER AND REGISTRY URL

NA.
The role of polysubstance use on criminal justice involvement in the United States
Authors: Jones Abenaa A. , Strong-Jones Sienna , Apsley Hannah B.
Published: May 2023

Purpose of review

Polysubstance use, broadly defined as using more than one type of substance, disproportionately impacts those involved in the criminal justice system (CJS). This review synthesizes recent findings on polysubstance use among those involved in the CJS and highlights areas of particular concern and interventions.

Recent findings

We use 18 recent articles to identify the prevalence and types of criminal justice involvement and correlates of polysubstance use and criminal justice involvement. We highlight latent patterns of polysubstance use among various criminal justice populations (adults, pregnant women, and youth) and differential associations with adverse substance use and criminal justice outcomes. Lastly, we discuss substance use treatment in the justice system, the role of polysubstance use in treatment access and outcomes, and substance use-related services for previously incarcerated individuals reentering society.

Current research provides further evidence of the syndemic nature of polysubstance use, criminal justice involvement, and adverse outcomes, which are complicated by significant barriers to accessing evidence-based treatment in justice settings. Yet, current research is limited due to methodological inconsistency and limited focus on the social determinants of health, racial/ethnic disparities, and interventions to increase treatment and reentry services.
Predictors and motives of polydrug use in opioid users. A narrative review
Authors: van Amsterdam Jan , Pierce Mimi , van den Brink Wim
Published: May 2023

Purpose of review

To review the recent literature on predictors and personal motives of polydrug use in opioid users with a focus on combined use of opioids with stimulants, benzodiazepines and gabapentinoids.

Recent findings

In North America, methamphetamine is now the most prevalent co-drug in opioid users and is responsible for high mortality rates. In Europe, opioids are rather combined with either cocaine, benzodiazepines or gabapentionoids, but recent data are lacking.

Main personal motives of opioid users to combine opioids with methamphetamine or cocaine is to boost the opioid high, inhibit the withdrawal effects of heroin and have a cheaper alternative to maintain the opioid high. Risk factors of polydrug use by opioid users included being male, younger age, homelessness, high-risk sexual behavior, needle sharing, incarceration, poor mental health and recent use of cocaine or prescription opioids. The motives for co-use of opioids and gabapentinoids also include seeking a better high, lower price and to self-medicate pain/physical symptoms, including those resulting from withdrawal.

When treating opioid users with polydrug drug use, special attention should be paid to dosing when in opioid agonist methadone/buprenorphine treatment and to the presence of physical pain. The validity of part of the personal motives seems questionable which deserves attention when counselling opioid users with polydrug use.
University Student-led Public Engagement Event: Increasing Audience Diversity and Impact in a Non-Science Space
Authors: Lacey Melissa , Capper-Parkin Kelly , Schwartz-Narbonne Rachel , Hargreaves Kate , Higham Catherine , Duckett Catherine , Forbes Sarah , Rawlinson Katherine
Published: May 2023

There is a wealth of innovation in microbiology outreach events globally, including in the setting where the public engagement is hosted. Previous data indicates underrepresentation of marginalised ethnic groups attending UK science-based public engagement events. This project engaged our student cohort, encompassing a diverse range of ethnic groups, to create an integrated art and science event within an existing series of adult education evenings. The study’s objectives were to increase the proportion of visitors from marginalised ethnic groups and to gain a greater understanding of the impact of the event on the visitors’ reported science capital. The participants' demographics, links to our students and University, and detailed impact on participants' science capital of the event were determined through analysis of exit questionnaires. There was an increase in the proportion of marginalised ethnic group visitors compared to similar previous events. A higher proportion of visitors from marginalised ethnic groups had links with our students and University compared to white/white British visitors. Elements of the exit-questionnaire were mapped to the science capital framework and participants' science capital determined. Both ethnically marginalised participants and white/white British visitors showed an increase in science capital, specifically dimensions of science-related social capital and science-related cultural capital, after the event. In conclusion, our study suggests that a student-led blended art and science public engagement can increase the ethnic diversity of those attending and can contribute towards creating more inclusive public engagement events.
Male-killer symbiont screening reveals novel associations in Adalia ladybirds
Authors: Archer Jack , Hurst Gregory D D , Hornett Emily
Published: May 2023

While male-killing bacteria are known to infect across arthropods, ladybird beetles represent a hotspot for these symbioses. In some host species, there are multiple different symbionts that vary in presence and frequency between populations. To further our understanding of spatial and frequency variation, we tested for the presence of three male-killing bacteria: Wolbachia, Rickettsia and Spiroplasma, in two Adalia ladybird species from a previously unexplored UK population. The two-spot ladybird, A. bipunctata, is known to harbour all three male-killers, and we identified Spiroplasma infection in the Merseyside population for the first time. However, in contrast to previous studies on two-spot ladybirds from continental Europe, evidence from egg hatch rates indicates the Spiroplasma strain present in the Merseyside population does not cause embryonic male-killing. In the related ten-spot ladybird, A. decempunctata, there is only one previous record of a male-killing symbiont, a Rickettsia, which we did not detect in the Merseyside sample. However, PCR assays indicated the presence of a Spiroplasma in a single A. decempunctata specimen. Marker sequence indicated that this Spiroplasma was divergent from that found in sympatric A. bipunctata. Genome sequencing of the Spiroplasma-infected A. decempunctata additionally revealed the presence of cobionts in the form of a Centistesparasitoid wasp and the parasitic fungi Beauveria. Further study of A. decempunctata from this population is needed to resolve whether it is the ladybird or wasp cobiont that harbours Spiroplasma, and to establish the phenotype of this strain. These data indicate first that microbial symbiont phenotype should not be assumed from past studies conducted in different locations, and second that cobiont presence may confound screening studies aimed to detect the frequency of a symbiont in field collected material from a focal host species.
Antribacter soli sp. nov., a novel actinobacterium isolated from soils of weathering dolomite
Authors: Zhang Ya , Gao Yuan , Yao Jiaqi , Liu Lingxiao , Ma Zhouai , Cao Cheng Liang , Li Rongpeng , Jiang Jihong , Liu Jinjuan
Published: May 2023

Strain KLBMP 9083T, a novel actinobacterium, was isolated from weathered soils collected from a karst area in Anshun, Guizhou Province, PR China. The taxonomic position of strain KLBMP 9083T was studied using the polyphasic approach. Phylogenetic analysis based on the 16S rRNA gene sequence indicated that strain KLBMP 9083T formed a stabilized monophyletic clade with its closest relative strain

Antribacter gilvus

CGMCC 1.13856T (98.4 % 16S rRNA gene sequence similarity). The peptidoglycan hydrolysates contained alanine, glutamic acid, threonine and lysine. The polar lipids were composed of diphosphatidylglycerol, phosphatidylinositol, phosphatidylinositol mannoside, an unidentified phosphoglycolipid, an unidentified phospholipid and an unidentified glycolipid. The predominant menaquinones were MK-9(H8) (87.1 %), MK-9(H6) (7.3 %) and MK-9(H4) (5.6 %). The major fatty acids (>10 %) were anteiso-C15 : 0 and iso-C15 : 0. The genomic DNA G+C content was 72.3 mol%. The digital DNA–DNA hybridization and average nucleotide identity values between strain KLBMP 9083T and

A. gilvus

CGMCC 1.13856T were 23.4 and 79.9 %, respectively. On the basis of morphological, chemotaxonomic and phylogenetic characteristics, strain KLBMP 9083T represents a novel species of the genus

Antribacter

, for which the name Antribacter soli sp. nov. is proposed. The type strain is KLBMP 9083T (=CGMCC 4.7737T=NBRC 115577T).
Respiratory Fungal Communities are Associated with Systemic Inflammation and Predict Survival in Patients with Acute Respiratory Failure
Authors: Britton Noel , Yang Haopu , Fitch Adam , Li Kelvin , Seyed Khaled , Guo Rui , Qin Shulin , Zhang Yingze , Bain William , Shah Faraaz , Biswas Partha , Choi Wonseok , Finkelman Malcolm , Zhang Yonglong , Haggerty Catherine L. , Benos Panayiotis V. , Brooks Maria M. , McVerry Bryan J. , Methe Barbara , Kitsios Georgios D. , Morris Alison
Published: May 2023

Rationale

Disruption of respiratory bacterial communities predicts poor clinical outcomes in critical illness; however, the role of respiratory fungal communities (mycobiome) is poorly understood.

Objectives

We investigated whether mycobiota variation in the respiratory tract is associated with host-response and clinical outcomes in critically ill patients.

Methods

To characterize the upper and lower respiratory tract mycobiota, we performed rRNA gene sequencing (internal transcribed spacer) of oral swabs and endotracheal aspirates (ETA) from 316 mechanically-ventilated patients. We examined associations of mycobiome profiles (diversity and composition) with clinical variables, host-response biomarkers, and outcomes.

Measurements and Main Results

ETA samples with >50% relative abundance forC. albicans(51%) were associated with elevated plasma IL-8 and pentraxin-3 (p=0.05), longer time-to-liberation from mechanical ventilation (p=0.04) and worse 30-day survival (adjusted hazards ratio (adjHR): 1.96 [1.04-3.81], p=0.05). Using unsupervised clustering, we derived two clusters in ETA samples, with Cluster 2 (39%) showing lower alpha diversity (p<0.001) and higher abundance ofC. albicans(p<0.001). Cluster 2 was significantly associated with the prognostically adverse hyperinflammatory subphenotype (odds ratio 2.07 [1.03-4.18], p=0.04) and predicted worse survival (adjHR: 1.81 [1.03-3.19], p=0.03).C. albicansabundance in oral swabs was also associated with the hyper-inflammatory subphenotype and mortality.

Conclusions

Variation in respiratory mycobiota was significantly associated with systemic inflammation and clinical outcomes.C. albicansabundance emerged as a negative predictor in both the upper and lower respiratory tract. The lung mycobiome may play an important role in the biological and clinical heterogeneity among critically ill patients and represent a potential therapeutic target for lung injury in critical illness.
A first-in-human study in healthy subjects of the safety and pharmacokinetics of CNM-Au8, a suspension of catalytically active gold nanocrystals with remyelinating and neuroprotective properties
Authors: Kanhai KMS , Zuiker RGJA , Houghton W , Kramer WG , McBride K , Moerland M , Dorfman Adam , McGlothlin Misty , Hotchkin M , Mortenson M , Etherington R , Groeneveld GJ
Published: May 2023

CNM-Au8 is a suspension of catalytically-active gold nanocrystals, developed to treat neurodegenerative disease. A first-in-human single- and multiple-ascending dose study was performed to assess safety and pharmacokinetics of CNM-Au8. The single-dose phase enrolled 40 subjects; the multiple-dose phase 48 subjects. Doses ranged from 15 to 90 mg CNM-Au8 and were administered by qualified clinical staffper os. Safety was assessed by adverse events, vitals, ECGs and laboratory measurements.

The most frequently reported related adverse event was mild abdominal pain (20%) of transient nature. Plasma half-life was 11.5 to 26.2 days, a first dose tmaxranged from 3.3 - 3.5 hours. CNM-Au8 displayed a safety profile and pharmacokinetic properties supportive of its advancement to Phase 2 and Phase 3 clinical trials.
Quantifying Clinical Trial Diversity of FDA Novel Drug Approvals
Authors: Fitzsimmons William E , Idris Muhammed Y , Pemu Priscilla
Published: May 2023

Background

Health care inequity includes the lack of adequate representation of various populations in clinical trials. Government, academic and industry organizations have highlighted these issues and committed to actions to improve. In order to assess the current status and future success of these initiatives a quantitative objective measure to assess the state of clinical trial diversity is needed.

Methods

FDA review documents for all novel drug approvals from January 2022 through February 16, 2023 were assessed using a scorecard that considers diversity across different demographic subgroups including age (>65 yo), sex (female), race (Black and Asian) and ethnicity (Hispanic/Latino). The scorecard assigns each drug a letter grade, between A and F, for each subgroup (and overall) based on 1) the percent of each sub-population included in the trials and grades relative to the percent of the US population, 2) the number of participants from each subpopulation that received the novel new drug in the trials, 3) the incidence or prevalence of the disease/condition in each of the sub-populations.

Results

The FDA approved 43 novel new drugs for 44 indications (one drug was simultaneously approved for two indications). The three drugs with A Grades reflecting the best diversity in their registration trials were tapinarof (Vtama from Dermavant), daprodustat (Jesduvroq from GlaxoSmithKline) and eflapegrastim (Rolvedon from Spectrum Pharmaceuticals.) There was good representation of elderly and females with only two drugs receiving a D grade in either of these sub-populations. In contrast, Black and Hispanic representation was often inadequate with 4 drugs receiving F grades. There were 9 drugs (20%) where there were no Black participants receiving the novel new drug and an additional 14 approvals where there were <10 Black participants receiving the novel drug. The median number of Black participants receiving the investigational drug was 9. In the Hispanic/Latino population there were 2 approvals with no Hispanic participants receiving the novel drug and 14 approvals where there were < 10 Hispanic participants receiving the drug. The median number of Hispanic participants receiving the novel drug was 12.5.

Conclusions

This newly developed scorecard provides an objective quantitative approach to assess the current state of diversity in clinical trials supporting new drug approvals. Substantial improvement in racial and ethnic representation is needed. Meaningful change will require actions and cooperation amongst all stakeholders to address this multifaceted issue and will take commitment, perseverance, and appropriate incentives.
OCOsense™ smart glasses for analyzing facial expressions using optomyographic sensors
Authors: Archer James , Mavridou Ifigeneia , Stankoski Simon , Broulidakis M. John , Cleal Andrew , Walas Piotr , Fatoorechi Mohsen , Gjoreski Hristijan , Nduka Charles
Published: May 2023

This article introduces the Emteq’s OCOsense™ smart glasses equipped with a novel non-contact OCO™ sensor technology for measuring facial muscle activation and expressions based on high resolution tracking of skin movement. We demonstrate that the OCO™ sensor technology based on optomyography is a sensitive and accurate approach for assessing skin movement in 3 dimensions, providing a means for measuring the facial expressions used to assess emotional valence such as smile, frown, and eyebrow raise. We propose that glasses-based optomyography sensing has the potential to herald a paradigm shift in real-world facial expression monitoring, thus enabling real-time emotional analytics with healthcare and research applications.
Pediatric brain tumor classification using deep learning on MR-images from the children’s brain tumor network
Authors: Bianchessi Tamara , Tampu Iulian Emil , Blystad Ida , Lundberg Peter , Nyman Per , Eklund Anders , Haj-Hosseini Neda
Published: May 2023

Background and purpose

Brain tumors are among the leading causes of cancer deaths in children. Initial diagnosis based on MR images can be a challenging task for radiologists, depending on the tumor type and location. Deep learning methods could support the diagnosis by predicting the tumor type.

Materials and methods

A subset (181 subjects) of the data from “Children’s Brain Tumor Network” (CBTN) was used, including infratentorial and supratentorial tumors, with the main tumor types being low-grade astrocytomas, ependymomas, and medulloblastomas. T1w-Gd, T2-w, and ADC MR sequences were used separately. Classification was performed on 2D MR images using four different off-the-shelf deep learning models and a custom-designed shallow network all pre-trained on adult MR images. Joint fusion was implemented to combine image and age data, and tumor type prediction was computed volume-wise. Matthew’s correlation coefficient (MCC), accuracy, and F1 scores were used to assess the models’ performance. Model explainability, using gradient-weighted class activation mapping (Grad-CAM), was implemented and the network’s attention on the tumor region was quantified.

Results

The shallow custom network resulted in the highest classification performance when trained on T2-w or ADC MR images fused with age information, when considering infratentorial tumors only (MCC: 0.71 for ADC and 0.64 for T2-w), and both infra- and supratentorial tumors (MCC: 0.70 for ADC and 0.57 for T2-w).

Conclusion

Classification of pediatric brain tumors on MR images could be accomplished using deep learning, and the fusion of age information improved model performance.
Outbreak of a carbapenem-resistant XDRAcinetobacter baumanniibelonging to the International Clone II (IC2) in a clinical setting in Brazil, 2022
Authors: da Fonseca Érica Lourenço , Morgado Sérgio Mascarenhas , Santos Freitas Fernanda dos , Oliveira Priscila P. C. , Monteiro Priscilla M. , Lima Lorena S. , Santos Bianca P. , Sousa Maria Aparecida R. , Assunção Adriana O. , Mascarenhas Luís Affonso , Paulo Vicente Ana Carolina
Published: May 2023

Carbapenem-resistantAcinetobacter baumannii(CRAB) is a leading cause of nosocomial infections worldwide, and the occurrence of extensively drug-resistant (XDR) lineages among them is increasing. Most ofA. baumanniipandemic lineages, known as International clones, are represented by MDR/XDR CRAB strains. The IC2 is considered one of the most successful and widespread pandemic clones, however, it is rare in South America, where IC1, IC4 and IC5 are prevalent. In Brazil, besides sporadic reports, an IC2 outbreak was reported only once in São Paulo city during the COVID-19 pandemics. This study characterized an outbreak caused by IC2 strains (n=16) in a hospital in Rio de Janeiro in 2022. MLST (MLST Pasteur scheme) analysis revealed that all strains recovered from nosocomial infections belonged to ST2 and corresponded to CRAB presenting the XDR phenotype. In general, this broad resistance spectrum was explained by the presence of several antibiotic resistance genes (ARGs) (armA, blaTEM,blaOXA-23,blaOXA-66, andaacA4-catB8-aadA1-qacEΔ1/sul1carried in class 1 integron). Interestingly, the strains characterized here presented a broader resistance spectrum compared to those of the unique other and contemporary IC2 outbreak in Brazil, although they shared most of the ARGs. This study stressed the possibility of the successful establishment of IC2 in Brazilian clinical settings during and after the COVID-19 pandemics in response to a series of events, such as the overuse of antibiotics, during that period.
Polygenic risk scores validated in patient-derived cells stratify for mitochondrial subtypes of Parkinson’s disease
Authors: Arena Giuseppe , Landoulsi Zied , Grossmann Dajana , Vitali Armelle , Delcambre Sylvie , Baron Alexandre , Antony Paul , Boussaad Ibrahim , Bobbili Dheeraj Reddy , Sreelatha Ashwin Ashok Kumar , Pavelka Lukas , Klein Christine , Seibler Philip , Glaab Enrico , Sharma Manu , Krüger Rejko , May Patrick , Grünewald Anne
Published: May 2023

Background

Parkinson’s disease (PD) is the fastest growing neurodegenerative disorder, with affected individuals expected to double during the next 20 years. This raises the urgent need to better understand the genetic architecture and downstream cellular alterations underlying PD pathogenesis, in order to identify more focused therapeutic targets. While only ∼10% of PD cases can be clearly attributed to monogenic causes, there is mounting evidence that additional genetic factors could play a role in idiopathic PD (iPD). In particular, common variants with low to moderate effect size in multiple genes regulating key neuroprotective activities may act as risk factors for PD. In light of the well-established involvement of mitochondrial dysfunction in PD, we hypothesized that a fraction of iPD cases may harbour a pathogenic combination of common variants in nuclear-encoded mitochondrial genes, ultimately resulting in neurodegeneration.

Methods

to capture this mitochondria-related “missing heritability”, we leveraged on existing data from previous genome-wide association studies (GWAS) – i.e., the large PD GWAS from Nalls and colleagues. We then used computational approaches based on mitochondria-specific polygenic risk scores (mitoPRSs) for imputing the genotype data obtained from different iPD case-control datasets worldwide, including the Luxembourg Parkinson’s Study (412 iPD patients and 576 healthy controls) and the COURAGE-PD cohorts (7270 iPD cases and 6819 healthy controls).

Results

applying this approach to gene sets controlling mitochondrial pathways potentially relevant for neurodegeneration in PD, we demonstrated that common variants in genes regulatingOxidative Phosphorylation (OXPHOS-PRS)were significantly associated with a higher PD risk both in the Luxembourg Parkinson’s Study (odds ratio, OR=1.31[1.14-1.50],p=5.4e-04) and in COURAGE-PD (OR=1.23[1.18-1.27],p=1.5e-29). Functional analyses in primary skin fibroblasts and in the corresponding induced pluripotent stem cells-derived neuronal progenitor cells from Luxembourg Parkinson’s Study iPD patients stratified according to theOXPHOS-PRS, revealed significant differences in mitochondrial respiration between high and low risk groups (p< 0.05). Finally, we also demonstrated that iPD patients with highOXPHOS-PRS have a significantly earlier age at disease onset compared to low-risk patients.

Conclusions

our findings suggest that OXPHOS-PRS may represent a promising strategy to stratify iPD patients into pathogenic subgroups – in which the underlying neurodegeneration is due to a genetically defined mitochondrial burden – potentially eligible for future, more tailored mitochondrially targeted treatments.
Dissection of medical AI reasoning processes via physician and generative-AI collaboration
Authors: DeGrave Alex J. , Cai Zhuo Ran , Janizek Joseph D. , Daneshjou Roxana , Lee Su-In
Published: May 2023

Despite the proliferation and clinical deployment of artificial intelligence (AI)-based medical software devices, most remain black boxes that are uninterpretable to key stakeholders including patients, physicians, and even the developers of the devices. Here, we present a general model auditing framework that combines insights from medical experts with a highly expressive form of explainable AI that leverages generative models, to understand the reasoning processes of AI devices. We then apply this framework to generate the first thorough, medically interpretable picture of the reasoning processes of machine-learning–based medical image AI. In our synergistic framework, a generative model first renders “counterfactual” medical images, which in essence visually represent the reasoning process of a medical AI device, and then physicians translate these counterfactual images to medically meaningful features. As our use case, we audit five high-profile AI devices in dermatology, an area of particular interest since dermatology AI devices are beginning to achieve deployment globally. We reveal how dermatology AI devices rely both on features used by human dermatologists, such as lesional pigmentation patterns, as well as multiple, previously unreported, potentially undesirable features, such as background skin texture and image color balance. Our study also sets a precedent for the rigorous application of explainable AI to understand AI in any specialized domain and provides a means for practitioners, clinicians, and regulators to uncloak AI’s powerful but previously enigmatic reasoning processes in a medically understandable way.
Disrupted seasonality and association of COVID-19 with medically attended respiratory syncytial virus infections among young children in the US: January 2010–January 2023
Authors: Wang Lindsey , Davis Pamela B. , Berger Nathan A. , Kaelber David C. , Volkow Nora D. , Xu Rong
Published: May 2023

Respiratory syncytial virus (RSV) infections and hospitalizations surged sharply in 2022 among young children. To assess whether COVID-19 contributed to this surge, we leveraged a real-time nation-wide US database of electronic health records (EHRs) using time series analysis from January 1, 2010 through January 31, 2023, and propensity-score matched cohort comparisons for children aged 0–5 years with or without prior COVID-19 infection. Seasonal patterns of medically attended RSV infections were significantly disrupted during the COVID-19 pandemic. The monthly incidence rate for first-time medically attended cases, most of which were severe RSV-associated diseases, reached a historical high rate of 2,182 cases per 1,0000,000 person-days in November 2022, corresponding to a related increase of 143% compared to expected peak rate (rate ratio: 2.43, 95% CI: 2.25–2.63). Among 228,940 children aged 0–5 years, the risk for first-time medically attended RSV during 10/2022–12/2022 was 6.40% for children with prior COVID-19 infection, higher than 4.30% for the matched children without COVID-19 (risk ratio or RR: 1.40, 95% CI: 1.27–1.55); and among 99,105 children aged 0–1 year, the overall risk was 7.90% for those with prior COVID-19 infection, higher than 5.64% for matched children without (RR: 1.40, 95% CI: 1.21–1.62). These data provide evidence that COVID-19 contributed to the 2022 surge of severe pediatric RSV cases.
Spirituality, quality of life, and general health: a cross-sectional study
Authors: Yoshizawa Takeshi , Makram Abdelrahman M , Nakamura Sadako , Elsheikh Randa , Makram Engy Mohamed , Huy Nguyen Tien , Moji Kazuhiko
Published: May 2023

Background

Some researchers have highlighted the need to integrate spirituality into the definition of health, as they have found a positive relationship between spirituality and quality of life (QoL). Hence, we aim to ascertain the effect of spirituality on mental health and QoL in older people residing in Kumejima Town in Japan.

Methods

We conducted an interview-based survey between September 2010 and 2011 on people residing in Kumejima Town aged 65 years or older. The scale used was The Spirituality Health Scale for the Elderly. The survey includes items on basic attributes (e.g., age, sex); physical, mental, and social health; spirituality; and quality of life. The analysis was conducted on a causal structure model in which spirituality is a distinct item influencing QoL (Model 1) and a causal structure model in which spirituality poses direct and indirect effects on QoL (Model 2). For each model, we reported the goodness-of-fit in terms of the goodness-of-fit index (GFI), adjusted goodness-of-fit index (AGFI), comparative fit index (CFI), and root mean square error of approximation (RMSEA). To compare the models, we used the Akaike information criterion (AIC).

Results

The total number of participants was 338, of whom 72.5% were female. The average age and its standard deviation were 77.2 ± 6.4 years. We presented a comparison of the results of the analysis of Model 1 and Model 2, with the results favoring Model 2. Also, Model 2 was superior to Model 1 in terms of the AIC, where the value of the AIC is 313.67 for Model 2 compared to 330.48 for Model 1.

Conclusion

This study was able to show the possibility of preventing a decline in QoL until death by building up spiritual health. However, further studies are required to further investigate these outcomes in the wider population (Japanese and other nationalities) and with some focus on male participants.
Patterns of Failure for Recurrent Head and Neck Squamous Cell Carcinoma Treated with Salvage Surgery and Postoperative IMRT Reirradiation
Authors: Mohamed Abdallah S. R. , Martin Geoffrey V. , Ng Sweet Ping , Takiar Vinita , Beadle Beth M. , Zafereo Mark , Garden Adam S. , Frank Steven J. , Fuller C. David , Gunn G. Brandon , Morrison William H. , Rosenthal David I. , Reddy Jay , Moreno Amy , Lee Anna , Phan Jack
Published: May 2023

Purpose/Objectives

Determining the optimal postoperative reirradiation volume following salvage surgery for recurrent head and neck squamous cell cancer (HNSCC) is critical given the significant risk of severe reirradiation toxicity and need to provide durable local control. The purpose of this study was to evaluate patterns of locoregional recurrence (LRR) after surgical salvage and adjuvant reirradiation with IMRT.

Materials/Methods

Patterns of LRR for 61 patients treated consecutively between 2003-2014 who received post-operative IMRT reirradiation to ≥60 Gy for recurrent HNSCC were determined by 2 methods: 1) physician classification via visual comparison of post-radiotherapy imaging to reirradiation plans; and 2) using deformable image registration (DIR). Those without evaluable CT planning image data were excluded. All recurrences were verified by biopsy or radiological progression. Failures were defined as in-field, marginal, or out-of-field. Logistic regression analyses were performed to identify predictors for LRR.

Results

A total of 55 patients were eligible for analysis and 23 (42%) had documented LRR after reirradiation. Location of recurrent disease prior to salvage surgery (lymphatic vs. mucosal) was the only significant predictor of LRR after post-operative reirradiation (p = 0.037). Physician classification of LRR yielded 14 (61%) in-field failures, 3 (13%) marginal failures, and 6 (26%) out-of-field failures, while DIR yielded 10 (44%) in-field failures, 4 (17%) marginal failures, and 9 (39%) out-of-field failures. Most failures (57%) occurred within the original site of recurrence or first echelon lymphatic drainage. Of patients who had a free flap placed during salvage surgery, 56% of failures occurred within 1 cm of the surgical flap.

Conclusion

The majority of locoregional recurrences after surgical salvage and adjuvant reirradiation for recurrent HNSCC occurred marginally or in-field, often in or near the anastomotic site.
Significant Production of Ozone from Germicidal UV Lights at 222 nm
Authors: Peng Zhe , Day Douglas A. , Symonds Guy , Jenks Olivia , Stark Harald , Handschy Anne V. , de Gouw Joost , Jimenez Jose L.
Published: May 2023

Lamps emitting at 222 nm have attracted recent interest for germicidal ultraviolet disinfection (“GUV222”). Their impact on indoor air quality is considered negligible. In this study, ozone formation is observed for eight different lamps from five manufacturers, in amounts an order-of-magnitude larger than previous reports. Most lamps produce O3in amounts close to the first-principles calculation, with e.g. a generation rate of 22 ppb h-1for Ushio B1 modules in a 21 m3chamber. Much more O3is produced by lamps when optical filters were removed for tests, and by an undesired internal electrical discharge. A test in an office shows an increase of ∼6.5 ppb during lamp-on periods, consistent with a simple model with the O3generation rate, ventilation and O3losses. We demonstrate the use of a photolytic tracer to quantify the averaged GUV222 fluence rate in a room. Low-cost electrochemical O3sensors were not useful below 100 ppb. Formation of O3increases indoor particulate matter (PM), which is ∼10-30 times more deadly than O3per unit mass, and which is ignored when only considering O3threshold limit values. To limit GUV222-created indoor pollution, lower fluence rates should be used if possible, especially under low-ventilation conditions.

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Improvement in Expanded Disability Status Scale (EDSS) and anti-inflammatory parameters in patients with multiple sclerosis following oral consumption of N-163 strain ofAureobasidium pullulansproduced beta glucan in a pilot clinical study
Authors: Dedeepiya Vidyasagar Devaprasad , Vetrievel Chockanathan , Ikewaki Nobunao , Ichiyama Koji , Yamamoto Naoki , Kawashima Hiroto , Bharatidasan Sudhakar S , Srinivasan Subramaniam , Senthilkumar Rajappa , Preethy Senthilkumar , Abraham Samuel JK
Published: May 2023

Introduction

Multiple Sclerosis (MS) is a debilitating neurodegenerative disease in which demyelination due to auto-inflammation is considered to be the underlying pathogenesis, though the exact etiology is not known. Most of the management strategies involve medications that are anti-inflammatory or immune-suppressive, which do have associated side effects. In this study we have evaluated in MS patients, the clinical effects of a novel beta-glucan which has a track record of anti-inflammatory, immune-modulating potentials in earlier clinical and pre-clinical studies.

Method

The study involved 12 MS patients who consumed two sachets of N-163 strain ofAureobasidium pullulansproduced B-Glucan, daily for 60 days along with routine medication.

Results

The Expanded Disability Status Scale (EDSS) improved by 0.5 in two patients and by 1 in one patient post-intervention, worsened in 1 patient, remaining stable in the rest. Decrease in IL-6, improvement in CD4+ve, CD19+ve, CD3+ve, and CD8+ ve cell count, increase in Lymphocyte to C-reactive protein ratio (LCR), Leukocyte to CRP ratio (LeCR) and a decrease in Neutrophil to Lymphocyte ratio (NLR) were observed.

Conclusion

This study having proven the safety of N-163 strain ofA.pullulansproduced B-Glucan food supplement and the efficacy by improvement in the EDSS score, besides beneficial modulation of inflammation and immune parameters of relevance in MS patients in a short duration of 60 days, has significant potential as a disease modifying adjuvant in MS. Immunological parameters like NLR, LCR, LeCR correlating with clinical improvement, in line with earlier reports using the same beta-glucans, gain further significance for their potentials as biomarkers in MS.
Neoadjuvant chemotherapy and adjuvant chemotherapy are similarly beneficial for five-year overall survival in locally advanced gastric cancer patients
Authors: Birendra Kumar Sah , Zhenjia Yu , Sheng Lu , Yanan Zheng , Zhenglun Zhu , Jian Li , Chen Li , Min Yan , Zhenggang Zhu
Published: May 2023

Background

Different types of neoadjuvant chemotherapy regimens have been compared for gastric cancer, mostly in terms of radiological downgrading or pathological tumor regression; however, no large-scale multicenter RCT study has conducted a head-to-head comparison of the overall survival rate between perioperative or neoadjuvant chemotherapy(NAC) and postoperative or adjuvant chemotherapy(AC). We explored whether the five-year overall survival rate was greater in patients who received perioperative chemotherapy plus surgery than in those who underwent surgery first and then had postoperative chemotherapy.

Methods

Altogether, 77 patients with a clinical diagnosis of cTNM stage III were included. Five-year overall survival rates (OS) were compared between patients who underwent neoadjuvant chemotherapy plus surgery (NAC) and patients who underwent surgery first plus adjuvant chemotherapy (AC). Propensity score matching was applied to adjust for the disparity between the two groups. A Kaplan‒Meier plot was created for survival analysis, and the log rank method was used to compare the difference in OS.

Results

A total of 34 patients were in the NAC group, and 43 patients were in the AC group. There was no significant difference in age (median 64 vs. 66 years), cTNM staging, or extent of gastrectomy between the two groups (p<0.05).The median follow-up time was 58 months (range of 53-65 months). The five-year overall survival (OS) rates for the patients in the NAC group and AC group were 61.8% and 73.5%, respectively. There was no significant difference between the two groups in the five-year overall survival rates (p>0.05). There was no significant difference in the severity grading of postoperative complications between the two groups (p>0.05).

Conclusions

There was no significant difference in the five-year overall survival rate between the patients who underwent perioperative chemotherapy plus surgery and those who underwent surgery first plus postoperative chemotherapy. A well-controlled prospective study is necessary to reconfirm whether perioperative chemotherapy is superior to postoperative chemotherapy for gastric cancer patients.