bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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.
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.

Summary
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.

Summary
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.
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.
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

ABSTRACTRationaleDisruption of respiratory bacterial communities predicts poor clinical outcomes in critical illness; however, the role of respiratory fungal communities (mycobiome) is poorly understood.ObjectivesWe investigated whether mycobiota variation in the respiratory tract is associated with host-response and clinical outcomes in critically ill patients.MethodsTo 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 ResultsETA 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.ConclusionsVariation 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

AbstractCNM-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

AbstractBackgroundHealth 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.MethodsFDA 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.ResultsThe 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.ConclusionsThis 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

AbstractThis 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

ABSTRACTBackground and purposeBrain 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 methodsA 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.ResultsThe 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).ConclusionClassification 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

ABSTRACTCarbapenem-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.