bluuebunny/crossref_metadata_2025_split huggingface dataset:
Imipenem/funobactam (formerly XNW4107) in vivo pharmacodynamics against serine carbapenemase-producing Gram-negative bacteria: a novel modelling approach for time-dependent killing
Authors: Fratoni Andrew J , Berry Angela V , Liu Xiao , Chen Xi , Wu Yuchuan , Nicolau David P , Abdelraouf Kamilia 
Published: August 2023

Abstract

Background
Imipenem/funobactam (formerly XNW4107) is a novel β-lactam/β-lactamase inhibitor with activity against MDR Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacterales strains. Using a neutropenic murine thigh infection model, we aimed to determine the pharmacokinetic/pharmacodynamic (PK/PD) index, relative to funobactam exposure, that correlated most closely with the in vivo efficacy of imipenem/funobactam combination and the magnitude of index required for efficacy against serine carbapenemase-producing clinical strains.

Methods
Dose-fractionation was conducted against three strains. Imipenem human-simulated regimen (HSR, 500 mg q6h 1 h infusion) efficacy in combination with escalating funobactam exposures against seven A. baumannii, four P. aeruginosa and four Klebsiella pneumoniae (imipenem/funobactam MICs 0.25–16 mg/L) was assessed as 24 h change in log10cfu/thigh.

Results
Increased funobactam fractionation enhanced efficacy, indicating time-dependent killing. Changes in log10cfu/thigh versus %fT &gt; MIC were poorly predictive of efficacy; bactericidal activity was observed at %fT &gt; MIC = 0%. Across different threshold plasma funobactam concentrations (CTs), %fT &gt; CT(1 mg/L) had the highest correlation with efficacy. Normalizing the %fT &gt; CT = 1 mg/L index to the respective isolate imipenem/funobactam MIC ([%fT &gt; CT]/MIC) allowed integration of the isolate’s susceptibility, which further enhanced the correlation. Median (%fT &gt; CT[1 mg/L])/MIC values associated with 1-log reductions were 9.82 and 9.90 for A. baumannii and P. aeruginosa, respectively. Median (%fT &gt; CT[1 mg/L])/MIC associated with stasis was 55.73 for K. pneumoniae. Imipenem/funobactam 500/250 mg q6h 1 h infusion HSR produced &gt;1-log kill against 6/7 A. baumannii, 4/4 P. aeruginosa and stasis against 4/4 K. pneumoniae.

Conclusions
Imipenem/funobactam showed potent in vivo efficacy against serine carbapenemase-producers. The novel PK/PD index (%fT &gt; CT)/MIC appeared to best describe in vivo activity.
Automated identification of unstandardized medication data: a scalable and flexible data standardization pipeline using RxNorm on GEMINI multicenter hospital data
Authors: Waters Riley , Malecki Sarah , Lail Sharan , Mak Denise , Saha Sudipta , Jung Hae Young , Imrit Mohammed Arshad , Razak Fahad , Verma Amol A 
Published: August 2023

Abstract

Objective
Patient data repositories often assemble medication data from multiple sources, necessitating standardization prior to analysis. We implemented and evaluated a medication standardization procedure for use with a wide range of pharmacy data inputs across all drug categories, which supports research queries at multiple levels of granularity.

Methods
The GEMINI-RxNorm system automates the use of multiple RxNorm tools in tandem with other datasets to identify drug concepts from pharmacy orders. GEMINI-RxNorm was used to process 2 090 155 pharmacy orders from 245 258 hospitalizations between 2010 and 2017 at 7 hospitals in Ontario, Canada. The GEMINI-RxNorm system matches drug-identifying information from pharmacy data (including free-text fields) to RxNorm concept identifiers. A user interface allows researchers to search for drug terms and returns the relevant original pharmacy data through the matched RxNorm concepts. Users can then manually validate the predicted matches and discard false positives. We designed the system to maximize recall (sensitivity) and enable excellent precision (positive predictive value) with efficient manual validation. We compared the performance of this system to manual coding (by a physician and pharmacist) of 13 medication classes.

Results
Manual coding was performed for 1 948 817 pharmacy orders and GEMINI-RxNorm successfully returned 1 941 389 (99.6%) orders. Recall was greater than 0.985 in all 13 drug classes, and the F1-score and precision remained above 0.90 in all drug classes, facilitating efficient manual review to achieve 100% precision. GEMINI-RxNorm saved time substantially compared with manual standardization, reducing the time taken to review a pharmacy order row from an estimated 30 to 5 s and reducing the number of rows needed to be reviewed by up to 99.99%.

Discussion and Conclusion
GEMINI-RxNorm presents a novel combination of RxNorm tools and other datasets to enable accurate, efficient, flexible, and scalable standardization of pharmacy data. By facilitating efficient manual validation, the GEMINI-RxNorm system can allow researchers to achieve near-perfect accuracy in medication data standardization.
Relationships of genomic estimated breeding values for age at puberty, birth weight, and growth during development in normal cyclic and acyclic gilts
Authors: Wijesena Hiruni R , Nonneman Dan J , Rohrer Gary A , Lents Clay A 
Published: August 2023

Abstract
Managing replacement gilts to reach optimal body weight and growth rate for boar stimulation and first breeding is a key component for sow reproductive longevity and producer profitability. Failure to display pubertal estrus remains a major reason that gilts are culled from the herd. Puberty is metabolically gated so evaluating phenotypic and genetic relationships between birth weight and growth traits with age at puberty and acyclicity can provide valuable insight for efficient gilt development. Data on a litter of origin of the gilt, average daily gain at different stages of development, and age at puberty were available for age-matched cyclic (n = 4,861) and acyclic gilts (prepubertal anestrus, n = 578; behavioral anestrus, n = 428). Genomic estimated breeding values were predicted for each trait using genomic best linear unbiased prediction. Primiparous sows produced more acyclic gilts than multiparous sows (P &lt; 0.05). Accounting for effects of parity and litter size, prepubertal anestrus gilts were heavier at birth and behaviorally anestrus gilts grew faster during the finisher period compared to cyclic gilts (P &lt; 0.05), reflecting possible prenatal programming that negatively affects optimal pubertal development and antagonistic effects between adolescent growth and expression of estrus of gilts from first parity sows. Regression of phenotypic age at puberty with lifetime growth rate (birth to selection) showed a negative linear relationship whereas genomic estimated breeding values showed a negative quadratic relationship indicating that gilts with the least and greatest growth are less optimal as replacements. The slopes of these relationships are small with low negative phenotypic (r = –0.06) and genetic correlations (r = –0.13). The addition of data from acyclic gilts did not substantially change the estimates for genetic relationships between growth and pubertal onset. Although this study identified differences in birth weight and growth rate between cyclic and acyclic gilts the genetic relationships are weak, suggesting that genetic selection for these traits can be achieved separately. Avoiding the smallest and largest gilts in a cohort born to first parity sows could result in gilts with optimal development and reduce the proportion of replacement gilts that are acyclic.
Does Referral Distance Deteriorates the Burn Patients Outcome? Results From an Academic Tertiary Hospital in a Developing Country
Authors: Zeinalipour Zahra , Goldani Fatemeh , Khadem-Rezaiyan Majid , Ahmadabadi Ali , Tavousi Seyed Hassan 
Published: August 2023

Abstract
Every year millions of people are burned and many of them are transported to specialized burn centers. One of the most important challenges in the face of burn patients in urban areas is deciding about referring patients to specialized burn centers. In this study, correlation between referral distance and mortality rate is investigated. Our cross-sectional analytic study included admission data of 7248 burn patients from Imam Reza Burn Center (Mashhad, Iran) over 9 years. The outcomes of interest were mortality, length of hospital stay, and the Abbreviated Burn Severity Index (ABSI). Also, we measured the distance between the patient referral location to Mashhad. SPSS version 16 was used for data analysis. Overall, 52.7% of admitted patients were referred from hospitals in other cities. The referred group had more severe burn injury (P &lt; .001), higher mortality rate (P &lt; .001), and longer length of hospital stay (P &lt; .001). The referred distance was associated with an increased risk of death (Odds ratio = 1.68, 95% CI, 1.47–1.92), but after controlling the severity of burns, only ABSI was the statistically significant predictor of mortality (Odds ration = 2.17, 95% CI, 2.05–2.28). Therefore, increasing the distance from urban areas to specialized burn center did not increase the mortality rate. After adjusting for ABSI, the mortality rate in referred patients was not related to referral distance. By observing referral points based on available guidelines, distance from a referral burn center does not affect mortality rate independently. Therefore, equipping the existing burn centers instead of building new ones and focusing on improving referral system can be a good strategy in low- and middle-income countries with limited resources.
Management and Outcomes of Acute Kidney Injury due to Burns: A Literature Review
Authors: Khandelwal Anjay , Satariano Matthew , Doshi Kush , Aggarwal Pushan , Avasarala Vardhan , Sood Aneil , Bansal Shyam , Neyra Javier A , Raina Rupesh 
Published: August 2023

Abstract
Acute kidney injury (AKI), a common and severe complication following burn injuries, presents a significant challenge due to its broad clinical manifestations and diverse etiologies. AKI, previously known as acute renal failure, can present abruptly following burns or thermal injuries, causing detrimental health outcomes such as progressive kidney dysfunction, increased hospital length of stay, and requirement of renal replacement therapy (RRT). AKI affects the maintenance of homeostasis of fluid and electrolytes, elimination of metabolic wastes and byproducts, and acid–base balance. Aggressive nutritional support is particularly necessitated in burn patients to prevent protein-energy wasting and a negative nitrogen balance. Understanding the pathogenesis of AKI in burns and improving its prevention and early diagnosis are active areas of research in this field. Despite the potential benefits, the optimal timing and threshold for RRT initiation in burn patients with AKI remain unclear, warranting further studies. Ongoing investigations focus on refining RRT techniques, evaluating biomarkers for early detection of AKI, and exploring adjunctive therapies to enhance renal recovery. The aim of this study is to review the etiology, diagnostic tools, and interventions that improve outcomes associated with AKI in burn-related settings.
Introduction of the ectoparasite Rhipicephalus pulchellus (Ixodida: Ixodidae) into Connecticut with a human traveler from Tanzania, and a review of its importation records into the United States
Authors: Stafford Kirby C , Molaei Goudarz , Williams Scott C , Mertins James W 
Published: August 2023

Abstract
Globalization, increased frequency of travel, and a rise in legal and illegal animal trades can introduce exotic ticks into the United States. We herein report the importation of a male Rhipicephalus pulchellus (Gerstäcker) on a human traveler returning to Connecticut from Tanzania, Africa, and review historical importation records of this species into the United States. This common tick is broadly distributed throughout East Africa, from Eritrea to Tanzania, has a wide host range on domestic animals and wildlife, and has been most frequently introduced into the United States on tick-infested wild animal hosts and animal trophies, but documentation of importation on humans has been rare. Archival records at the United States Department of Agriculture’s National Veterinary Services Laboratories show R. pulchellus has been introduced into the United States at least 40 times over the last 62 yr. Rhipicephalus pulchellus has been linked to Rickettsia conorii, the agent of boutonneuse fever in humans, Crimean-Congo hemorrhagic fever orthonairovirus, and Nairobi sheep disease orthonairovirus. Given the potential for this exotic tick to introduce animal or human pathogens, proper surveillance, interception, identification, and reporting of these ticks are vital in protecting human and animal health.
Changes in amount and intensity of physical activity over time in breast cancer survivors
Authors: Marell Paulina S , Vierkant Robert A , Olson Janet E , Herrmann Joerg , Larson Nicole L , Lebrasseur Nathan K , D’Andre Stacy D , Ehlers Diane K , Stan Daniela L , Cheville Andrea L , Barksdale Toure , Loprinzi Charles L , Couch Fergus J , Ruddy Kathryn J 
Published: August 2023

Abstract

Background
Physical activity is associated with decreased breast cancer recurrence and mortality, as well as fewer treatment-related symptoms. Nevertheless, most breast cancer survivors do not meet physical activity guidelines. The purpose of this manuscript is to characterize physical activity trends over time in breast cancer survivors.

Methods
Mayo Clinic Breast Disease Registry participants received surveys at baseline and at 1 and 4 years after diagnosis; breast cancer recurrence and/or metastatic disease were exclusion criteria. Participants were considered to be meeting guidelines if they self-reported at least 150 minutes of moderate-intensity (eg, fast walking) and/or strenuous (eg, jogging) physical activity per week. Statistical analyses include analysis of covariance methods, paired t tests, conditional logistic regression models, and McNemar tests of homogeneity.

Results
A total of 171 participants were included in the analysis. The amount of total physical activity decreased over time (P = .07). Mild-intensity physical activity (eg, easy walking) decreased most over time (P = .05). Among participants aged 18-49 years, mild-intensity (P = .05) and moderate-intensity (P = .02) physical activity decreased over time. Strenuous-intensity physical activity levels decreased over time among participants with a normal body mass index (P = .002) and with obesity (P = .01).

Conclusions
We found a trend-level decrease in total physical activity over time, driven mostly by a decrease in mild-intensity physical activity. Young breast cancer survivors are especially likely to reduce their physical activity over time. Further research on implementing physical activity guidelines in clinical practice is warranted.
The numerical investigation of aerodynamics and aeroacoustics effects in a full-scale true wireless headphone
Authors: Wang Wei-Hsiang , Chang Hua-Ching , Cheng Ta-Yuan , Chen Yu-Chien 
Published: August 2023

Abstract
This study investigates the flow characteristics and aeroacoustic effects in a true wireless (TWS) headphone using computational fluid dynamics simulations. A low-speed compressible flow solver is employed to analyze the flow fields and pressure variations associated with fluid-induced noise. The accuracy of the simulations is validated through comparisons with experimental and numerical data, demonstrating good consistency. The analysis reveals the presence of asymmetric vortex shedding patterns, attributed to the angle of airflow and the irregular surface of the headphones. The examination of the microphone chamber highlights the significance of design parameters in shaping flow patterns and acoustics. Optimized designs have the potential to achieve noise reductions of up to 10.62% or amplifications of up to 24.95%. These findings contribute to the development of improved active noise cancellation systems and the enhancement of TWS headphone technology, aiming to reduce external noise and enhance sound quality.
Diathermy induced gas explosion during laparotomy: a case report
Authors: Sindani Martin , Lugwaja Paul William Itule , Ngowi Novath 
Published: August 2023

Abstract
Diathermy-induced explosions in the gastrointestinal tract can occur during laparotomy and can be fatal. Hydrogen and methane are the most common flammable gases that are produced in the gastrointestinal tract. A 35-year-old male was referred to a tertiary hospital with abdominal pain after being assaulted and stabbed in the abdomen. He presented with a 2-cm wound in the midline below the xiphoid process and with an omentum protruding through the wound. Explorative laparotomy was done to repair the jejunal perforation, but a gastric blast occurred, making more than half of the gastric pouch non-viable. The operation was converted to a near-total gastrectomy with Roux-en-Y gastrojejunostomy. During open abdominal surgery, fires and explosions can occur. Precautions should be taken during open abdominal surgery to reduce the risk of explosions, such as allowing combustible gases to exit the cavity before using diathermy.
Validation of the eHEALTH Literacy Scale (Eheals) With Military Service Members
Authors: Foote Douglas , Giger Jarod T , Murray Teresa D , Engelhardt Ethan , Flaherty Christopher 
Published: August 2023

ABSTRACT

Introduction
Medical readiness of individual service members (SMs) is an integral component of operational readiness. Electronic Health (eHealth) literacy, here defined as the ability to seek out, find, evaluate, and appraise, integrate, and apply what is gained in electronic environments toward solving a health problem, is a key skill to enhance individual medical readiness. The World Health Organization (WHO) has identified health literacy as an important social determinant of health. The Internet enables individuals to access information virtually anywhere, at any place, any time, which is especially beneficial for SMs who serve around the globe, often isolated from modern health care facilities.

Materials and Methods
This study examined the utility of the eHealth literacy scale (eHeals) as a potentially valuable tool to assist commanders and medical teams for assessing the health literacy of SMs. The main objective of our study was to examine the validity of the three-factor eHEALS measure for an active duty sample, using confirmatory factorial analysis.

Results
Our findings support the validity of the eHEALS measure of electronic health literacy among military SMs, potentially identifying a means of measuring SMs’ health literacy, and a target for intervention to increase medical readiness, well-being, and overall quality of life for individual SMs.

Conclusions
The study highlights a brief 6-item assessment tool that can quickly and efficiently be added to the current validated health and well-being measures for military personnel. This brief assessment can provide a measure of knowledge, skills, and confidence regarding ehealth information leading to better-informed health care decisions in the military context. These findings are especially relevant given the military’s current emphasis on modernization and the need to put people first in order to build the overall team and improve unit effectiveness.
Saquinavir potentiates itraconazole’s antifungal activity against multidrug-resistant Candida auris in vitro andin vivo
Authors: Elgammal Yehia , Salama Ehab A , Seleem Mohamed N 
Published: August 2023

Abstract
Candida species are highly opportunistic yeasts that are responsible for serious invasive fungal infections among immunocompromised patients worldwide. Due to the increase in drug resistance and incidence of infections, there is an urgent need to develop new antifungals and to identify co-drugs that can sensitize drug-resistant Candida to antifungals. The objective of this study was to assess the effect of saquinavir on the activity of azole antifungals against C. auris. The in vitro interaction of saquinavir and three azole antifungals (itraconazole, voriconazole, and fluconazole) was evaluated against a panel of C. auris isolates. The itraconazole/saquinavir combination exhibited a synergistic (SYN) relationship against all C. auris isolates tested with the fractional inhibitory concentration index ranging from 0.03 to 0.27. Moreover, a time-kill kinetics assay revealed that saquinavir restored the itraconazole’s fungistatic activity against C. auris. Furthermore, saquinavir restored itraconazole’s antifungal activity against other clinically important Candida species. The mechanistic investigation indicated that saquinavir significantly inhibited efflux pumps, glucose utilization, and ATP synthesis in Candida. Finally, a murine model of C. auris infection was used to evaluate the efficacy of the itraconazole/saquinavir combination in the presence of ritonavir (as a pharmacokinetic enhancer). The combination significantly reduced the fungal burden in the kidneys by 0.93-log10 colony-forming units (88%) compared to itraconazole alone. This study identified that saquinavir exhibits a potent SYN relationship in combination with itraconazole against Candida species, which warrants further consideration.
Significantly enhanced superconductivity in monolayer FeSe films on SrTiO3(001) via metallic δ-doping
Authors: Jiao Xiaotong , Dong Wenfeng , Shi Mingxia , Wang Heng , Ding Cui , Wei Zhongxu , Gong Guanming , Li Yanan , Li Yuanzhao , Zuo Binjie , Wang Jian , Zhang Ding , Pan Minghu , Wang Lili , Xue Qi-Kun 
Published: August 2023

ABSTRACT
Superconductivity transition temperature (Tc) marks the inception of a macroscopic quantum phase-coherent paired state in fermionic systems. For 2D superconductivity, the paired electrons condense into a coherent superfluid state at Tc, which is usually lower than the pairing temperature, between which intrinsic physics including Berezinskii–Kosterlitz–Thouless transition and pseudogap state are hotly debated. In the case of monolayer FeSe superconducting films on SrTiO3(001), although the pairing temperature (Tp) is revealed to be 65–83 K by using spectroscopy characterization, the measured zero-resistance temperature (${{T}}_{{\rm c}}^0$) is limited to 20 K. Here, we report significantly enhanced superconductivity in monolayer FeSe films by δ-doping of Eu or Al on SrTiO3(001) surface, in which ${{T}}_{{\rm c}}^0$ is enhanced by 12 K with a narrowed transition width ΔTc ∼ 8 K, compared with non-doped samples. Using scanning tunneling microscopy/spectroscopy measurements, we demonstrate lowered work function of the δ-doped SrTiO3(001) surface and enlarged superconducting gaps in the monolayer FeSe with improved morphology/electronic homogeneity. Our work provides a practical route to enhance 2D superconductivity by using interface engineering.