bluuebunny/crossref_metadata_2025_split huggingface dataset:
Postcardiac Arrest Care Delivery in Pediatric Intensive Care Units: A Plan and Call to Action
Authors: Barreto Jessica A. , Wenger Jesse , Dewan Maya , Topjian Alexis , Roberts Joan ,   for the pediatric Resuscitation Quality (pediRES-Q) Collaborative Investigators
Published: May 2024

Background:
Despite national pediatric postcardiac arrest care (PCAC) guidelines to improve neurological outcomes and survival, there are limited studies describing PCAC delivery in pediatric institutions. This study aimed to describe PCAC delivery in centers belonging to a resuscitation quality collaborative.

Methods:
An institutional review board-approved REDCap survey was distributed electronically to the lead resuscitation investigator at each institution in the international Pediatric Resuscitation Quality Improvement Collaborative. Data were summarized using descriptive statistics. A chi-square test was used to compare categorical data.

Results:
Twenty-four of 47 centers (51%) completed the survey. Most respondents (58%) belonged to large centers (>1,000 annual pediatric intensive care unit admissions). Sixty-seven percent of centers reported no specific process to initiate PCAC with the other third employing order sets, paper forms, or institutional guidelines. Common PCAC targets included temperature (96%), age-based blood pressure (88%), and glucose (75%). Most PCAC included electroencephalogram (75%), but neuroimaging was only included at 46% of centers. Duration of PCAC was either tailored to clinical improvement and neurological examination (54%) or time-based (45%). Only 25% of centers reported having a mechanism for evaluating PCAC adherence. Common barriers to effective PCAC implementation included lack of time and limited training opportunities.

Conclusions:
There is wide variation in PCAC delivery among surveyed pediatric institutions despite national guidelines to standardize and implement PCAC.
Synergizing Safety: A Customized Approach to Curtailing Unplanned Extubations through Shared Decision-making in the NICU
Authors: Krishnan Parvathy , Jawale Nilima , Sodikoff Adam , Malfa Susan R. , McCarthy Kathleen , Strickrodt Lisa M. , D’Agrosa Diana , Pickard Alexandra , Parton Lance A. , Singh Meenakshi 
Published: May 2024

Background:
Unplanned Extubation (UE) remains an important patient safety issue in the Neonatal Intensive Care Unit. Our SMART AIM was to decrease the rate of UE by 10% from the baseline from January to December 2022 by emphasizing collaboration among healthcare professionals and through the use of shared decision-making.

Methods:
We established an interdisciplinary Quality Improvement team composed of nurses, respiratory therapists, and physicians (MDs). The definition of UE was standardized. UE was audited using an apparent cause analysis form to discern associated causes and pinpoint areas for improvement. Interventions were implemented in a step-by-step fashion and reviewed monthly using the model for improvement. A shared decision-making approach fostered collaborative problem-solving.

Results:
Our baseline UE rate was 2.3 per 100 ventilator days. Retaping, general bedside care, and position change accounted for over 50% of the UE events in 2022. The rate of UE was reduced by 48% by the end of December 2022. We achieved special-cause variation by the end of March 2023.

Conclusions:
The sole education of medical and nursing providers about various approaches to decreasing unnecessary retaping was ineffective in reducing UE rates. Shared decision-making incorporating inputs from nurses, respiratory therapists, and MDs led to a substantial reduction in the UE rate and underscores the potential of systematic evaluation of risk factors combined with collaborative best practices.
Perinatal Use and Discontinuation of Disease-Modifying Antirheumatic Drugs
Authors: Rebić Nevena , De Vera Mary A. , Gupta Amit , Amiri Neda 
Published: May 2024

Background
Managing rheumatic disease activity using pregnancy-compatible medications is essential for reducing adverse maternal and fetal outcomes. We characterized medication use and discontinuation before, during, and after pregnancy, among female patients with rheumatic diseases attending a targeted pregnancy and rheumatic diseases clinic.

Methods
We conducted a cross-sectional medical record review of female patients with rheumatic diseases at a Canadian clinic between January 2017 and July 2020. Patients were categorized by pregnancy stage at their latest clinic visit: (1) preconception; (2) pregnant; (3) postpartum. We assessed use of conventional, biologic, and targeted synthetic disease-modifying antirheumatic drugs (DMARDs), prednisone, and nonsteroidal anti-inflammatory drugs across 6 perinatal windows: 24 and 12 months preconception, each pregnancy trimester, and 3 months postpartum. We reported adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for medication discontinuation in the first trimester and subsequent disease flare.

Results
Of 230 included patients, 85 (37.0%), 12 (5.2%), and 133 (57.8%) were preconception, pregnant, and postpartum, respectively. Approximately half experienced at least 1 disease flare during each pregnancy stage (56.4% preconception, 58.1% during pregnancy, and 53.7% postpartum). Most used at least 1 DMARD throughout the perinatal period (82.6% preconception, 55.6% during pregnancy, and 45.1% postpartum). Overall, 25.5% discontinued at least 1 DMARD in the first trimester. DMARD discontinuation was associated with disease flare during pregnancy (aOR, 1.49; 95% CI, 0.55–4.03; p = 0.87) and postpartum (aOR, 3.09; 95% CI, 0.83–11.47; p = 0.09).

Conclusions
Patients receiving care at a pregnancy and rheumatic disease clinic show perinatal medication use patterns consistent with recent recommendations and clinical guidelines.
Not All Days Were Created Equal—Better Day Orientation Following the Weekend on Mini-Mental State Examination (MMSE)
Authors: Shefet Daphna , Lurie Ido 
Published: May 2024

Objective:
The aim of this study was to test whether patients are better oriented to the day on the first working day following the weekend (in Israel—Sunday), compared with other weekdays, on the Mini-Mental Score Examination (MMSE).

Methods:
All MMSE scores from November 2016 until December 2022 in our mental health center’s computerized system were collected. The proportion of correct answers to orientation to the day was compared between weekdays.

Results:
The cohort consisted of 2049 MMSEs taken by 1376 patients [average age 80.3 (SD=9.3), 56.4% female]. The difference between the proportion of correct and incorrect answers was statistically significant between the days, of which Sundays showed a larger difference (53.4%) compared with the other days (χ2=20.77, P<0.001, Cramer V=0.104). A statistically significant odds ratio (OR) for providing a correct response was found for Sundays (OR=1.55, P=0.001) and, to a lesser extent, on Thursdays (OR=1.29, P=0.01). The difference between Sundays and other weekdays disappears as the total MMSE decreases.

Conclusion:
Day orientation on the MMSE may be better on the first day following the weekend, especially in early cognitive decline.

Clinical Implications:
The weekday in which the MMSE is performed may influence its results.
Spontaneous Dimerization and Distinct Packing Modes of Transmembrane Domains in Receptor Tyrosine Kinases
Authors: Levintov Lev , Gorai Biswajit , Vashisth Harish 
Published: May 2024

AbstractThe insulin receptor (IR) and the insulin-like growth factor-1 receptor (IGF1R) are homodimeric transmembrane glycoproteins that transduce signals across the membrane on binding of extracellular peptide ligands. The structures of IR/IGF1R fragments in apo and liganded states have revealed that the extracellular subunits of these receptors adopt Λ-shaped configurations to which are connected the intracellular tyrosine kinase (TK) domains. The binding of peptide ligands induces structural transitions in the extracellular subunits leading to potential dimerization of transmembrane domains (TMDs) and autophosphorylation in TKs. However, the activation mechanisms of IR/IGF1R, especially the role of TMDs in coordinating signal-inducing structural transitions, remain poorly understood, in part due to the lack of structures of full-length receptors in apo or liganded states. While atomistic simulations of IR/IGF1R TMDs showed that these domains can dimerize in single component membranes, spontaneous unbiased dimerization in a plasma membrane having physiologically representative lipid composition has not been observed. We address this limitation by employing coarsegrained (CG) molecular dynamics simulations to probe the dimerization propensity of IR/IGF1R TMDs. We observed that TMDs in both receptors spontaneously dimerized independent of their initial orientations in their dissociated states, signifying their natural propensity for dimerization. In the dimeric state, IR TMDs predominantly adopted X-shaped configurations with asymmetric helical packing and significant tilt relative to the membrane normal, while IGF1R TMDs adopted symmetric V-shaped or parallel configurations with either no tilt or a small tilt relative to the membrane normal. Our results suggest that IR/IGF1R TMDs spontaneously dimerize and adopt distinct dimerized configurations.TOC Graphic
A Single Dose of Inactivated Influenza Virus Vaccine Expressing COBRA Hemagglutinin Elicits Broadly-Reactive and Long-Lasting Protection
Authors: Shi Hua , Zhang Xiaojian , Ross Ted M. 
Published: May 2024

AbstractInfluenza virus infections present a pervasive global health concern resulting in millions of hospitalizations and thousands of fatalities annually. To address the influenza antigenic variation, the computationally optimized broadly reactive antigen (COBRA) methodology was used to design influenza hemagglutinin (HA) or neuraminidase (NA) for universal influenza vaccine candidates. In this study, whole inactivated virus (WIV) or split inactivated virus (SIV) vaccine formulations expressing either the H1 COBRA HA or H3 COBRA HA were formulated with or without an adjuvant and tested in ferrets with pre-existing anti-influenza immunity. A single dose of the COBRA-WIV vaccine elicited a robust and broadly reactive antibody response against H1N1 and H3N2 influenza viruses. In contrast, the COBRA-SIV elicited antibodies that recognized fewer viruses, but with R-DOATP, its specificity was expanded. Vaccinated ferrets were protected against morbidity and mortality following challenge with A/California/07/2009 at 14 weeks post-vaccination with reduced viral shedding post-infection compared to the naïve mock-vaccinated ferrets. However, the COBRA-IIVs did not block the viral transmission to naïve ferrets. The contact infection induced less severe disease and delayed viral shedding than direct infection. Overall, the COBRA HA WIV or the COBRA HA SIV plus R-DOTAP elicited broadly reactive antibodies with long-term protection against viral challenge and reduced viral transmission following a single dose of vaccine in ferrets pre-immune to historical H1N1 and H3N2 influenza viruses.IMPORTANCEA next-generation influenza virus vaccine aims to provide broadly reactive protection against various drifted influenza strains. COBRA HA-based vaccines elicit broadly-reactive antibodies following two or three vaccinations. However, people are administered a single vaccination of current commercial influenza virus vaccines. In this study, ferrets with pre-existing anti-influenza immunity were administered a single shot COBRA-WIV that elicited long-lasting, broadly-reactive antibodies that protected ferrets against pdmH1N1 viral challenge. This is the first study describing the immune responses elicited by COBRA-IIV vaccines in ferrets that protected ferrets 14 weeks post-vaccination.
Measuring autofluorescence spectral signatures for detecting antibiotic-resistant bacteria using Thermofisher’s Bigfoot spectral flow cytometer
Authors: Iyengar Sharath Narayana , Patsekin Valery , Rajwa Bartek , Bae Euiwon , Dowden Brianna , Ragheb Kathy , Robinson J Paul 
Published: May 2024

AbstractApplication of flow cytometry to microbiology has been limited due to inadequate availability of bacterial-specific stains, expensive antibody-based fluorophores, ineffective stain cell permeability and challenges in differentiating bacterial cells from cell debris due to their similarity and their small size. In addition, staining cells demands multiple washing steps which limits the sensitivity of detection due to the cell volume that is up to two orders smaller than typical eukaryotic cells. Further, most flow cytometers are not equipped to handle pathogenic organisms. Autofluorescence-based detection of cells can be a useful method for bacterial detection as multiple washing steps can be avoided and it also reduces the time and cost of using stains. Multiple studies have shown that the autofluorescence in bacterial cells are mainly linked to specific proteins, enzymes, or enzyme cofactors such as Flavin Adenine Dinucleotide (FAD) and Nicotinamide Adenine Dinucleotide (NAD) which are involved in bacterial metabolism. In this report, we present a novel method for differentiation between clinically isolated antibiotic resistant and non-resistant bacteria by utilizing their autofluorescence spectral signatures. We utilized a spectral cytometer known as Bigfoot which is equipped with an integrated biosafety cabinet allowing easy handling of pathogenic organisms unlike any other flow cytometers. Bigfoot also has 9 lasers and 54 fluorescence detectors which we utilize to capture the bacterial spectral autofluorescence signatures. As a proof of principle, we initially stressed different types of bacteria (E.coli and Salmonella sp.)using gentamicin antibiotics by collecting spectral autofluorescence over different time points. The spectral signatures were compared with the non-stressed bacteria. We observed that the stressed bacteria showed an increase in autofluorescence at distinct excitation (Ultraviolet, Violet, and blue color) and emission wavelengths whereas the non-stressed did not. The same experiments were repeated to compare the autofluorescence signatures between Methicillin-resistant and methicillin susceptiblestaphylococcus aureus(MRSA and MSSA) which were stressed with oxacillin antibiotics. MSSA showed an increase in autofluorescence between 4 – 6 h after exposure to oxacillin. MRSA on the other hand showed no increase in autofluorescence and the autofluorescence between stressed and non-stressed MRSA had similar signatures. This demonstrated that the antibiotic resistant or susceptible strain can be detected by observing the change in autofluorescence signature at specific wavelengths in a few hours. This label-free, quantitative, and resistant-specific autofluorescence spectral signatures from the Bigfoot spectral flow cytometer could potentially be utilized for rapid detection of antibioticresistant strain.
Mechanophysiology of endometriosis: a non-dimensional physiomarker to detect retrograde flow
Authors: Elisha Guy , Patankar Neelesh A. 
Published: May 2024

AbstractEndometriosis affects a significant portion of fertile-age women, often leading to infertility and a substantial decline in quality of life. Despite its prevalence, current diagnostic methods are limited, focusing on assessing the presence or absence of endometrial lesion, rather than the origin of the disorder. Thus, resulting in underdiagnosis. A potential mechanics-based metric for diagnosing endometriosis is proposed here by leveraging the retrograde menstruation hypothesis. By examining the interplay between uterine and fallopian tube peristalses, a non-dimensional physiomarker is introduced to signify the onset of retrograde flow. The analysis reveals that increased uterine contractile activity, coupled with decreased fallopian tube contractile activity, correlates with retrograde flow, suggesting a predisposition to endometriosis. This mechanophysiology-based approach offers a promising avenue for origin based diagnosis, with the proposed non-dimensional physiomarker – the endometriosis number – serving as a potential indicator of endometrial cell migration and the onset of endometriosis.
Oral Exposure to Benzalkonium Chlorides in Male and Female Mice Reveals Sex-Dependent Alteration of the Gut Microbiome and Bile Acid Profile
Authors: Lopez Vanessa A. , Lim Joe L. , Seguin Ryan P. , Dempsey Joseph L. , Kunzman Gabrielle , Cui Julia Y. , Xu Libin 
Published: May 2024

AbstractBenzalkonium chlorides (BACs) are commonly used disinfectants in a variety of consumer and food-processing settings, and the COVID-19 pandemic has led to increased usage of BACs. The prevalence of BACs raises the concern that BAC exposure could disrupt the gastrointestinal microbiota, thus interfering with the beneficial functions of the microbes. We hypothesize that BAC exposure can alter the gut microbiome diversity and composition, which will disrupt bile acid homeostasis along the gut-liver axis. In this study, male and female mice were exposed orally to d7-C12- and d7-C16-BACs at 120 µg/g/day for one week. UPLC-MS/MS analysis of liver, blood, and fecal samples of BAC-treated mice demonstrated the absorption and metabolism of BACs. Both parent BACs and their metabolites were detected in all exposed samples. Additionally, 16S rRNA sequencing was carried out on the bacterial DNA isolated from the cecum intestinal content. For female mice, and to a lesser extent in males, we found that treatment with either d7-C12- or d7-C16-BAC led to decreased alpha diversity and differential composition of gut bacteria with notably decreased actinobacteria phylum. Lastly, through a targeted bile acid quantitation analysis, we observed decreases in secondary bile acids in BAC-treated mice, which was more pronounced in the female mice. This finding is supported by decreases in bacteria known to metabolize primary bile acids into secondary bile acids, such as the families of Ruminococcaceae and Lachnospiraceae. Together, these data signify the potential impact of BACs on human health through disturbance of the gut microbiome and gut-liver interactions.
AdipocytemicroRNA-802promotes adipose tissue inflammation and insulin resistance by modulating macrophages in obesity
Authors: Yang Yue , Huang Bin , Qin Yimeng , Wang Danwei , Jin Yinuo , Su Linmin , Pan Yi , Zhang Yanfeng , Shen Yumeng , Hu Wenjun , Cao Zhengyu , Jin Liang , Zhang Fangfang 
Published: May 2024

AbstractAdipose tissue inflammation is now considered to be a key process underlying metabolic diseases in obese individuals. However, it remains unclear how adipose inflammation is initiated and maintained or the mechanism by which inflammation develops. We found thatmicroRNA-802(miR-802) expression in adipose tissue is progressively increased with the development of dietary obesity in obese mice and humans. The increasing trend ofmiR-802preceded the accumulation of macrophages. Adipose tissue-specific knockout ofmiR-802lowered macrophage infiltration and ameliorated systemic insulin resistance. Conversely, the specific overexpression ofmiR-802in adipose tissue aggravated adipose inflammation in mice fed a high-fat diet. Mechanistically,miR-802activates noncanonical and canonical NF-κB pathways by targeting its negative regulator, TRAF3. Next, NF-κB orchestrated the expression of chemokine and SREBP1, which translated into strong recruitment and M1-like polarization of macrophages. Our findings indicate thatmiR-802endows adipose tissue with the ability to recruit and polarize macrophages, which underscoresmiR-802as an innovative and attractive candidate for miRNA-based immune therapy for adipose inflammation.
Shared genetics between breast cancer and its predisposing diseases identify novel breast cancer treatment candidates
Authors: Lalagkas Panagiotis N. , Melamed Rachel D. 
Published: May 2024

AbstractBreast cancer is a major public health issue. Current treatment options, while effective, have severe side effects. FDA-approved drugs have known safety and pharmacological profiles and some, such as metformin, have been tested in clinical trials for repurposing for breast cancer. However, clinical trials are slow and expensive, which creates the need for innovative approaches to accelerate drug repurposing for breast cancer. We have previously shown that genes associated with Mendelian diseases that predispose patients to certain cancers are enriched for successful drug targets, due to their pleiotropic effects. Here, we extend our approach to exploit clinical associations between breast cancer and its predisposing diseases for drug repurposing. We hypothesize that pleiotropic genes shared between breast cancer and its predisposing diseases can help us discover new uses for drugs currently approved only for the predisposing diseases. To test our hypothesis, we compile a list of six traits known to increase breast cancer risk (predisposing diseases). Using GWAS summary statistics and local genetic correlation analysis, we find 84 genomic loci harboring mutations with positively correlated effects between breast cancer and each predisposing disease. These loci contain 194 protein-coding genes (shared genes). Using a network biology approach and canonical pathways, for each disease pair, we connect drugs already indicated for the predisposing disease to its shared biology with breast cancer and identify drug repurposing candidates for breast cancer. Finally, we show that our list of candidate drugs is enriched for currently investigated and indicated drugs for breast cancer (OR=9.28, p=7.99e-03). Our findings suggest a novel way to accelerate drug repurposing for complex diseases by leveraging shared genetics.
Bioarchaeological Perspectives on Late Antiquity in Dalmatia: Paleogenetic, Dietary, and Population Studies of the Hvar - Radošević burial site
Authors: Zagorc Brina , Blanz Magdalena , Gelabert Pere , Sawyer Susanna , Oberreiter Victoria , Cheronet Olivia , Chen Hao Shan , Carić Mario , Visković Eduard , Olalde Iňigo , Ivanova-Bieg Maria , Novak Mario , Reich David , Pinhasi Ron 
Published: May 2024

AbstractLate Antiquity Dalmatia was a time and place of political unrest in the Roman Empire that influenced the lives of the people living in that region. The Late Antique burial site of Hvar – Radošević, spanning the 3rdto 5thcenturies, is located on the Croatian Dalmatian island of Hvar. Given the time frame and its location on a busy marine trade route, study of this burial site offers us a glimpse into the lives of the Late Antique population living on this island. It comprises 33 individuals, with 17 buried within a confined grave tomb, and the remaining individuals buried in separate locations in the tomb’s proximity. Our objective was to provide new perspectives on the lives of people on the island during those times by studying ancestry, population structure, possible differences within the buried population, dietary habits, and general health.Analysis of the ancestral origins of the individuals buried at Hvar – Radošević revealed a diverse population reflective of the era’s genetic variability. The identification of genetic outliers suggests affiliations with distinct regions of the Roman Empire, possibly linked to trade routes associated with the Late Antique port in ancient Hvar. Stable isotope ratio analysis (δ¹³C and δ¹⁵N) indicated a diet mainly consisting of C3plants, with minimal consumption of marine foods. High childhood mortality rates, physiological stress markers, and dental diseases suggest a low quality of life in the population. Assessment of kinship and dietary patterns revealed no discernible distinctions between individuals buried within the tomb and those buried outside, indicative of an absence of differential burial practices based on social status and familial ties.