bluuebunny/crossref_metadata_2025_split huggingface dataset:
Landlord CVAs
Authors: Asimacopoulos Kon , Watterson Adam , Fleming Richard , Kennedy Clare , Butters Dan , Wright Will 
Published: May 2024

Abstract
This chapter focuses on the phases and development of CVAs proposed by companies as a means of modifying or compromising landlord claims. It also discusses the use of tenant companies' CVAs that are part of a listed group, where a parent company's shares are registered on a regulated stock exchange. Due to the Global Financial Crisis and subsequent global recession, traditional retail business models were experiencing the impact of change in the industry in line with the rapid development of internet technologies and digitisation of businesses. Moreover, numerous landlord CVAs successfully implemented by public companies are listed on stock exchanges.
Semileptonic W Decay to the B Meson with Lepton Pairs in Heavy Quark Effective Theory Factorization up to $\mathcal {O}(\alpha _s)$
Authors: Ishaq Saadi , Zafar Sajawal , Rehman Abdur , Ahmed Ishtiaq 
Published: May 2024

Abstract
Motivated by the study of heavy–light meson production within the framework of heavy quark effective theory (HQET) factorization, we extend the factorization formalism for a rather complicated process W+ → B+ℓ+ℓ− in the limit of a nonzero invariant squared mass of the dilepton, q2, at the lowest order in 1/mb up to $\mathcal {O}(\alpha _s)$. The purpose of the current study is to extend the HQET factorization formula for the W+ → B+ℓ+ℓ− process and subsequently compute the form factors for this channel up to next-to-leading-order corrections in αs. We explicitly show that the amplitude of the W+ → B+ℓ+ℓ− process can also be factorized into a convolution between the perturbatively calculable hard-scattering kernel and the nonperturbative yet universal light-cone distribution amplitude (LCDA) defined in HQET. The validity of the HQET factorization depends on the assumed scale hierarchy mW ∼ mb ≫ ΛQCD. Within the HQET framework, we evaluate the form factors associated with the W+ → B+ℓ+ℓ− process, providing insights into its phenomenology. In addition, we also perform an exploratory phenomenological study on W+ → B+ℓ+ℓ− by employing an exponential model for the LCDAs for the B+ meson. Our findings reveal that the branching ratio for W+ → B+ℓ+ℓ− is below 10−10. Although the branching ratios are small, this channel in high-luminosity LHC experiments may serve to further constrain the value of λB.
Should We Prevent Off-Label Drug Prescriptions? Empirical Evidence from France
Authors: Tunçel Tuba 
Published: May 2024

Abstract
After a drug obtains marketing authorisation, the usage depends on the regulation of off-label prescriptions for unapproved indications. We investigate the impact of off-label prescription regulation on physicians’ behaviour, patients’ health, treatment costs, and pharmaceutical firms’ pricing with a structural demand and supply model. Exploiting rich panel data on physicians’ activities and office visits in France over 9 years, we use a model of prescription choice and health outcomes with unobserved patient-level heterogeneity. We identify the demand for on-label and off-label drugs and the effect of prescription choice on health outcomes. On the supply side, we use a Nash-in-Nash bargaining model between the government and the pharmaceutical companies that allows the partial identification of the marginal costs of drugs. Counterfactual simulations show that when we remove off-label drugs from the choice set of physicians, substitution to on-label drugs at constant prices would lead to an increase of 15% in the expenditure on prescription drugs. If we allow bargaining adjustment on drug prices under a ban on off-label prescriptions, the ban would further increase the treatment cost, by 26%, without improving health outcomes.
Prevalence and Diversity of Aphid-Vectored Yellow Dwarf Viruses in Oregon Perennial Grass Seed Crops
Authors: Rivedal Hannah M. , Dorman Seth J. , Temple Todd N. , Lockwood Thomas C. , Walenta Darrin L. , Oshiro Chloe , Cruse Casey , Starchvick Robert J. , Woodward Makenna M. , Anderson Nicole P. 
Published: May 2024

Oregon produces 70% of the world's cool-season grass seed, many species of which are susceptible to yellow dwarf viruses (YDVs). This virus complex has numerous defined virus species vectored by multiple aphid species. The diversity of YDVs associated with Oregon grass seed production has not been determined and is needed to provide insight to develop a risk prediction framework and improve management guidelines to mitigate disease severity. Commercial grass seed fields ( n = 57) across the Willamette Valley and central and eastern Oregon were surveyed across 2021 and 2022 to determine the incidence and diversity of YDVs associated with crop species (perennial ryegrass, tall fescue, and Kentucky bluegrass) and the abundance and incidence of YDVs associated with aphid vectors. Virus incidence and diversity were determined using multiple previously published endpoint reverse-transcriptase multiplexes specific for YDV genera and species. Across commercial grass seed crop hosts and growing seasons, 82% of fields had at least one plant sample detection of a luteovirus-type YDV, and 65% had at least one detection of a polerovirus-type YDV. Both perennial ryegrass and tall fescue crops hosted diverse YDV populations, which was especially apparent during the spring sampling season, when similarly diverse YDV communities were found associated with alate aphids. Only polerovirus-type YDVs were detected in Kentucky bluegrass, reflecting a variable landscape compared to Oregon's western Willamette Valley. This study provides a current understanding of the spatial composition and diversity of the aphid–YDV virus–vector system in grasses grown for seed in Oregon. [Formula: see text] The author(s) have dedicated the work to the public domain under the Creative Commons CC0 “No Rights Reserved” license by waiving all of his or her rights to the work worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law, 2024.
Biological sex differences in pain response and functional outcomes after orthopedic surgery procedures: a scoping review
Authors: Allen Jack , Zumwalt Mimi 
Published: May 2024

Background/Objective:
Post-operative pain is frequently experienced by patients following orthopedic surgery procedures despite improved surgical technology and anesthesia techniques. The intensity of postoperative pain is multifactorial and biological sex is a key component of pain analysis. In this review article, the authors examine the impact of biological sex on post-operative pain scores and surgical outcomes following orthopedic surgery procedures.

Methods:
A keyword-based search of the National Library of Medicine and the National Center for Biotechnology Information was utilized for this review. Through our literature search we identified 56 articles related to the impact of sex on post-operative pain. These studies were then tabulated and analyzed in detail to provide data for this review article.

Results:
There are a variety of factors that influence surgical outcomes in orthopedics including age, comorbidities, and biological sex. The reviewed studies found that women report higher pain scores in the initial 6 wk post-operative period after total joint arthroplasty, upper extremity surgery, spine surgery, and general orthopedic surgery. Female sex was also associated with higher opioid consumption following surgery. In addition, men tend to have better surgical outcomes following total joint arthroplasty, upper extremity procedures, and spine surgery.

Discussion/Conclusion:
Biological differences including hormones, anatomy, and psychosocial factors influence post-operative pain differences between sexes. Little data is available on orthopedic surgery post-operative pain scores between the sexes and therefore further research is needed. Biological sex must be considered when evaluating patient wellness following orthopedic surgery procedures.
Addressing the Healthcare Needs of Transgender Youth in the Emergency Department
Authors: Mazzawi Malek , Maxwell Angela 
Published: May 2024

Abstract
Transgender is a term that refers to individuals who identify with a gender that is different from the sex assigned to them at birth. In addition to gender dysphoria, many transgender youth experience a number of challenges including homelessness, violence, and mental health problems such as suicidality. Although transgender people represent a growing subset of the population, most providers receive very little training specific to the unique healthcare needs of transgender patients. In this CME review article, we define relevant terminology then discuss best practices for clinical encounters involving transgender youth in the emergency department. Finally, we review gender-affirming care including behavioral modifications, hormones, and surgeries for transfeminine and transmasculine individuals.
A NOVEL CIRC_SUPT3/MIR-185-5P/G3BP2 CERNA NETWORK REGULATES HIGH GLUCOSE–INDUCED INJURY IN MOUSE PODOCYTE MPC5 CELLS
Authors: Li Yuting , Wang Wenyan , Liu Na , Wang Kexie , Ren Fei 
Published: May 2024

ABSTRACT

Background: Diabetic nephropathy (DN) is a complication of diabetes that is the leading cause of death in diabetic patients. Circular RNA (circRNA) is a hot topic in the research of human diseases. However, the role of circ_Supt3 in DN remains unclear. Methods: High glucose (HG) treatment of mouse podocyte (MPC5) cells to mimic DN cell injury. Quantitative real-time polymerase chain reaction was performed to detect the expression of circ_Supt3, microRNA-185-5p (miR-185-5p), and GTPase-activating protein-binding protein 2 (G3bp2). 5-Ethynyl-2′-deoxyuridine (EdU) and 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium Bromide (MTT) assays were used to examine cell proliferation, and flow cytometry was used to detect cell apoptosis. Western blot was used to assess the levels of relative proteins. Enzyme-linked immunosorbent assay detected the inflammation cytokines. Dual-luciferase reporter and RNA pull-down assays were used to confirm the interaction of miR-185-5p and circ_Supt3 or G3bp2. Results: Circ_Supt3 and G3bp2 were highly expressed and miR-185-5p expression was diminished in DN mice. HG treatment inhibited cell proliferation and accelerated cell apoptosis and inflammation response, and the knockdown of circ_Supt3 reversed these effects. Bioinformatics predicted that circ_Supt3 contained a binding site for miR-185-5p, and G3bp2 was a direct target of miR-185-5p. Circ_Supt3 regulated G3bp2 expression by miR-185-5p. Moreover, the circ_Supt3/miR-185-5p/G3bp2 axis regulated the cell behavior of HG-induced MPC5 cells. Conclusion: Our findings suggest that the knockdown of circ_Supt3 protects mouse MPC5 cells against HG-induced cell injury via the miR-185-5p/G3bp2 axis.
PLASMA DYNAMICS OF NEUTROPHIL EXTRACELLULAR TRAPS AND CELL-FREE DNA IN SEPTIC AND NONSEPTIC VASOPLEGIC SHOCK: A PROSPECTIVE COMPARATIVE OBSERVATIONAL COHORT STUDY
Authors: Coupland Lucy A. , Spiro Calista , Quah Benjamin J-C. , Orlov Anna , Browne Anna , O’Meara Connor H. , Kang Chang-Won , Frost Steve , Schulz Luis , Lombardo Lien , Parish Christopher R. , Aneman Anders 
Published: May 2024

ABSTRACT

Background: The association between neutrophil extracellular traps (NETs) and the requirement for vasopressor and inotropic support in vasoplegic shock is unclear. This study aimed to investigate the dynamics of plasma levels of NETs and cell-free DNA (cfDNA) up to 48 h after the admission to the intensive care unit (ICU) for management of vasoplegic shock of infectious (SEPSIS) or noninfectious (following cardiac surgery, CARDIAC) origin. Methods: This is a prospective, observational study of NETs and cfDNA plasma levels at 0H (admission) and then at 12H, 24H, and 48H in SEPSIS and CARDIAC patients. The vasopressor inotropic score (VIS), the Sequential Organ Failure Assessment (SOFA) score, and time spent with invasive ventilation, in ICU and in hospital, were recorded. Associations between NETs/cfDNA and VIS and SOFA were analyzed by Spearman’s correlation (rho), and between NETs/cfDNA and ventilation/ICU/hospitalization times by generalized linear regression. Results: Both NETs and cfDNA remained elevated over 48 h in SEPSIS (n = 46) and CARDIAC (n = 30) patients, with time-weighted average concentrations greatest in SEPSIS (NETs median difference 0.06 [0.02–0.11], P = 0.005; cfDNA median difference 0.48 [0.20–1.02], P < 0.001). The VIS correlated to NETs (rho = 0.3–0.60 in SEPSIS, P < 0.01, rho = 0.36–0.57 in CARDIAC, P ≤ 0.01) and cfDNA (rho = 0.40–0.56 in SEPSIS, P < 0.01, rho = 0.38–0.47 in CARDIAC, P < 0.05). NETs correlated with SOFA. Neither NETs nor cfDNA were independently associated with ventilator/ICU/hospitalization times. Conclusion: Plasma levels of NETs and cfDNA correlated with the dose of vasopressors and inotropes administered over 48 h in patients with vasoplegic shock from sepsis or following cardiac surgery. NETs levels also correlated with organ dysfunction. These findings suggest that similar mechanisms involving release of NETs are involved in the pathophysiology of vasoplegic shock irrespective of an infectious or noninfectious etiology.
Worth the Risk? Standardized Screening to Identify Substance Use Among Patients Prior to Surgery
Authors: Cooley Samantha , Bicket Mark C , Mohammed Hanan , Lai Yenling , Evilsizer Sarah , Brummett Chad M , Waljee Jennifer F. 
Published: May 2024

Objective:
We sought to compare identification of unhealthy substance use before surgery using The Tobacco, Alcohol, Prescription Medication, and Other Substance Use (TAPS), a standardized 4-item instrument, versus routine clinical documentation in the electronic medical record (EHR).

Summary Background Data:
Over 20% of individuals exhibit unhealthy substance use before elective surgery. Routine EHR documentation is often based on non-standard questions that may not fully capture the extent of substance use and is subject to bias. In contrast, brief standardized screening could provide a more efficient and systematic approach.

Methods:
We conducted a cross-sectional study among adults (≥18 y) at a preoperative clinic from August to September, 2021. Positive screens for unhealthy substances by TAPS were compared to data from the EHR. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were reported. Receiver operating characteristic curves (ROCs) were used to assess diagnostic ability. Multivariable logistic regression was used to estimate the predictors of positive screens by TAPS.

Results:
The cohort included 240 surgical patients. TAPS screening identified significantly more positive screens than EHR documentation (43.3% vs. 14.2%). Patients with unhealthy substance use were younger (50.8 vs. 56.7 y; P=0.003), and TAPS revealed alcohol misuse in 30.8% of cases, contrasting with 0% in clinician documentation (P<0.001). Of the 104 TAPS-positive patients, 69.2% were missed by EHR documentation. Sensitivity (31%) and accuracy (AUC=0.65) of clinician documentation for any unhealthy substance use were lower compared to TAPS.

Conclusion:
Standardized TAPS screening detected preoperative unhealthy substance use more frequently than routine clinician documentation, emphasizing the need for integrating standardized measures into surgical practice to ensure safer perioperative care and outcomes.
Cytoduction preserves genetic diversity following plasmid transfer into pooled yeast libraries
Authors: Jhuang Han-Ying , Aggeli Dimitra , Lang Gregory I. 
Published: May 2024

AbstractMuch of our understanding of functional genomics derives from insights gained from large strain libraries including the yeast deletion collection, the GFP and TAP-tagged libraries, QTL mapping populations, among others [1-5]. A limitation of these libraries is that it is not easy to introduce reporters or make genetic perturbations to all strains in these collections. Tools such as Synthetic Genetic Arrays allow for the genetic manipulation of these libraries but are labor intensive and require specialized equipment for high throughput pinning [6]. Manipulating a diverse libraryen masswithout losing diversity remains challenging. Ultimately, this limitation stems from the inefficiency of transformation, which is the standard method for genetic manipulation in yeast. Here, we develop a method that uses cytoduction (mating without nuclear fusion) to transfer plasmids directionally from a “Donor” to a diverse pool of “Recipient” strains. Because cytoduction uses mating, it is a natural process and is orders-of-magnitude more efficient than transformation, enabling the introduction of plasmids into high-diversity libraries with minimal impact on the diversity of the population.
Computer simulations reveal mechanisms of spatio-temporal regulation of DNA replication
Authors: Yousefi Razie , Rowicka Maga 
Published: May 2024

AbstractThe dynamics of DNA replication, activation of replication origins and elongation rate, depend on dNTP in ways that remain poorly understood. Here, we present RepliSim, a probabilistic computer model of DNA replication simulation, which is capable of simulating DNA replication not only in normal conditions, but also during perturbations (e.g. HU treatment) and in mutant cells (here checkpoint deficient yeast cells). We show that different mutations in checkpoint genes, affect the origin activation differently by modulating the stochasticity of firing time and efficiency, regardless of the dNTP levels. The origin activation is less affected by increase in dNTP levels, however it declined drastically during the S phase when the dNTP levels decreased compared to G1 phase. Additionally, we show that the distribution of distances covered by replication forks is influenced not only by average fork progression speed, but also by firing time and fork progression speed stochasticity, while the latter has been neglected in most of the proposed models for DNA replication. These together, opens up new insight to the studies about the dynamics of replication and how it is coordinated during the S-phase.
Photoreceptor loss does not recruit neutrophils despite strong microglial activation
Authors: Power Derek , Elstrott Justin , Schallek Jesse 
Published: May 2024

AbstractIn response to central nervous system (CNS) injury, tissue resident immune cells such as microglia and circulating systemic neutrophils are often first responders. The degree to which these cells interact in response to CNS damage is poorly understood, and even less so, in the neural retina which poses a challenge for high resolution imaging in vivo. In this study, we deploy fluorescence adaptive optics scanning light ophthalmoscopy (AOSLO) to study fluorescent microglia and neutrophils in mice. We simultaneously track immune cell dynamics using label-free phase-contrast AOSLO at micron-level resolution. Retinal lesions were induced with 488 nm light focused onto photoreceptor (PR) outer segments. These lesions focally ablated PRs, with minimal collateral damage to cells above and below the plane of focus. We used in vivo (AOSLO, SLO and OCT) imaging to reveal the natural history of the microglial and neutrophil response from minutes-to-months after injury. While microglia showed dynamic and progressive immune response with cells migrating into the injury locus within 1-day after injury, neutrophils were not recruited despite close proximity to vessels carrying neutrophils only microns away. Post-mortem confocal microscopy confirmed in vivo findings. This work illustrates that microglial activation does not recruit neutrophils in response to acute, focal loss of photoreceptors, a condition encountered in many retinal diseases.
In VivoSimvastatin and Brain Radiation in a Model of HER2+Inflammatory Breast Cancer Brain Metastasis
Authors: Kumar Swaminathan , Larson Richard A. , Stecklein Shane , Reddy Jay , Debeb Bisrat G. , Amos Richard A. , Cologna Stephanie M. , Woodward Wendy A. 
Published: May 2024

ABSTRACTPurposeInhibiting HMG-CoA reductase with simvastatin prevents breast cancer metastases in preclinical models and radiosensitizes monolayer and stem-like IBC cell linesin vitro. Given the extensive use of simvastatin worldwide and its expected penetration into the brain, we examined whether regulating cholesterol with simvastatin affected IBC3 HER2+ brain metastases.Methods and MaterialsBreast cancer cell lines KPL4 and MDA-IBC3 were examined in vitro for DNA repair after radiation with or without statin treatment. Brain metastasis endpoints were examined in the MDA-IBC3 brain metastasis model after ex vivo exposure to lipoproteins and after tail vein injections with and without whole-brain radiotherapy (WBR) and oral statin exposure.ResultsEx vivopreculture of MDA-IBC3 cells with very low-density lipoprotein (vLDL) enhanced the growth of colonized lesions in the brainin vivocompared with control or high-density lipoprotein (HDL), and concurrent oral simvastatin/ WBR reduced the incidence of micrometastatic lesions evaluated 10 days after WBR. However, statin, with or without WBR, did not reduce the incidence, burden, or number of macrometastatic brain lesions evaluated 5 weeks after WBR.ConclusionsAlthough a role for cholesterol biosynthesis is demonstrated in DNA repair and response to whole brain radiation in this model, durable in vivo efficacy of concurrent whole brain irradiation and oral statin was not demonstrated.
Kermut: Composite kernel regression for protein variant effects
Authors: Groth Peter Mørch , Kerrn Mads Herbert , Olsen Lars , Salomon Jesper , Boomsma Wouter 
Published: May 2024

AbstractReliable prediction of protein variant effects is crucial for both protein optimization and for advancing biological understanding. For practical use in protein engineering, it is important that we can also provide reliable uncertainty estimates for our predictions, and while prediction accuracy has seen much progress in recent years, uncertainty metrics are rarely reported. We here provide a Gaussian process regression model, Kermut, with a novel composite kernel for modeling mutation similarity, which obtains state-of-the-art performance for supervised protein variant effect prediction while also offering estimates of uncertainty through its posterior. An analysis of the quality of the uncertainty estimates demonstrates that our model provides meaningful levels of overall calibration, but that instance-specific uncertainty calibration remains more challenging.