bluuebunny/crossref_metadata_2025 huggingface dataset:
Lower Admission Prealbumin and Albumin Levels in Unhoused Burn Patients Is a Marker for Poorer Outcomes
Authors: Donohue Sean J , Baca Joseph , Speiser Noah , Pickering Trevor , Pham Christopher , Gillenwater Justin T , Yenikomshian Haig A
Published: May 2024

Unhoused (UH) individuals experience burn injuries at a higher rate than domiciled individuals, and have poorer outcomes following injuries. One such mechanism proposed for worsened outcomes is secondary to poor nutrition. Access to proper nutrition and food insecurity are major barriers. Malnutrition has been shown to decrease wound tensile strength, increase infection rates, and prolong healing. The purpose of this study was to understand if albumin and prealbumin could help determine outcomes in UH patients and identify at-risk patients earlier in their hospital course. A retrospective chart review was conducted of UH patients from 2015 through 2023 at a large urban safety net hospital. Data collected included admission laboratory values including albumin and prealbumin. Outcomes studied included length of stay (LOS), Intensive Care Unit (ICU) days, ventilator days, and mortality. Data analysis for the effect of albumin and prealbumin included a zero-truncated negative binomial model for LOS, a negative binomial hurdle model for ICU LOS and ventilator days, and logistic regression for mortality. Three hundred and eighty-five patients met inclusion criteria and of these, 366 had albumin and 361 had prealbumin information. Adjusting for age, gender, and total body surface area, the fewest days in the hospital and lowest odds of admission to the ICU occurred for those with admission albumin values of approximately 3.4-3.5 g/dL. Each unit (g/dL) decrease in albumin was associated with 3.19 times the odds of death (95% CI: 1.42, 7.69). Each unit (mg/dL) decrease in prealbumin was associated with 1.19 times the odds of death (95% CI: 1.06, 1.35). Decreased admission albumin and prealbumin levels are associated with worse burn outcomes in UH patients. These nutritional biomarkers may aid in determining which UH patients are suffering from food insecurity at injury onset. Obtaining these values on admission may help burn providers target nutritional goals in their most vulnerable patients.
Facilitating Culturally Competent Breast Imaging Care in South Asian Patients
Authors: Sharma Nidhi , Mehta Tejas S , Wahab Rifat A , Patel Miral M
Published: May 2024

South Asians are a rapidly growing subset of the Asian population in the United States. They comprise people from multiple countries with diverse beliefs, languages, and cultural identities and values. The incidence of breast cancer is rising in South Asian women in the United States, with earlier onset and predilection for HER2-enriched tumors. Despite the rising incidence of breast cancer, participation in screening remains lower than other populations. Health care inequities in South Asian women are multifactorial and may be due to traditional health beliefs and practices, language barriers, cultural differences, and lack of overall awareness. Developing a culturally sensitive environment in breast imaging clinic practice can lead to improved patient care and adherence. Given the scarcity of data specific to the South Asian population in United States, there is a need for health service researchers and practice leaders to obtain more high-quality data to understand the needs of South Asian patient populations.
Artificial neural network-based sequential approximate optimization of metal sheet architecture and forming process
Authors: Han Seong-Sik , Kim Heung-Kyu
Published: May 2024

This paper introduces a sequential approximate optimization method that combines the finite element method (FEM), dynamic differential evolution (DDE), and artificial neural network (ANN) surrogate models. The developed method is applied to address two optimization problems. The first involves metamaterial design optimization for metal sheet architecture with binary design variables. The second pertains to optimizing process parameters in multi-stage metal forming, where the discrete nature arises owing to changing tool geometries across stages. This process is highly non-linear, accumulating contact, geometric, and material non-linear effects discretely through forming stages. The efficacy of the proposed optimization method, utilizing ANN surrogate models, is compared with traditionally used polynomial response surface (PRS) surrogate models, primarily based on low-order polynomials. Efficient learning of ANN surrogate models is facilitated through the FEM and Python integration framework. Initial data for surrogate model training are collected via Latin hypercube sampling and FEM simulations. DDE is employed for sequential approximate optimization, optimizing ANN or PRS surrogate models to determine optimal design variables. PRS surrogate models encounter challenges in dealing with non-linear changes in sequential approximate optimization concerning discrete characteristics such as binary design variables and discrete non-linear behavior found in multi-stage metal forming processes. Owing to the discrete nature, PRS surrogate models require more data and iterations for optimal design variables. In contrast, ANN surrogate models adeptly predict non-linear behavior through the activation function’s characteristics. In the optimization problem of metal sheet architecture for design Target C, the ANN surrogate model required an average of 4.6 times fewer iterations to satisfy stopping criteria compared with the PRS surrogate model. Furthermore, in the optimization of multi-stage deep drawing processes, the ANN surrogate model required an average of 6.1 times fewer iterations to satisfy stopping criteria compared with the PRS surrogate model. As a result, the sequential global optimization method utilizing ANN surrogate models achieves optimal design variables with fewer iterations than PRS surrogate models. Further confirmation of the method’s efficiency is provided by comparing Pearson correlation coefficients and locus plots.
Capnodis tenebrionis (Coleoptera: Buprestidae), an important pest of stone fruits in the Mediterranean basin: current management strategies and prospects for integrated pest management
Authors: Nasouri Hussein
Published: May 2024

Capnodis tenebrionis (Linné) is a devastating pest of stone fruits (Prunus spp.) in the Mediterranean region. The endophytic root-boring larvae cause the main damage and can kill a large tree within 2 years. For several decades, with the absence of an effective biological control strategy, the management of this pest has mainly relied on the use of nonselective insecticides. These insecticides are applied either as a foliar spray targeting adults or as a soil treatment targeting neonate larvae. The search for alternative management options has increased since 2000 as a result of reduced efficacy of chemical control, decreased number of available insecticides, and the need for control measures suitable for organic stone fruit production. The main focus was on entomopathogenic nematodes and fungi. Several isolates/strains of these pathogens were found to be effective against larvae and adults of C. tenebrionis under laboratory and semi-field conditions. In this article, we review the current management options of C. tenebrionis, including chemical, biological, resilient rootstock, and cultural options. The prospects for developing an integrated management approach for this pest are also discussed.
Extracellular vesicles in cancer: golden goose or Trojan horse
Authors: Han Tao , Hao Qian , Chao Tengfei , Sun Qinggang , Chen Yitian , Gao Bo , Guan Liping , Ren Wenjie , Zhou Xiang
Published: May 2024

Intercellular communication can be mediated by direct cell-to-cell contact and indirect interactions through secretion of soluble chemokines, cytokines, and growth factors. Extracellular vesicles (EVs) have emerged as important mediators of cell-to-cell and cell-to-environment communications. EVs from tumor cells, immune cells, and stromal cells can remodel the tumor microenvironment and promote cancer cell survival, proliferation, metastasis, immune evasion, and therapeutic resistance. Most importantly, EVs as natural nanoparticles can be manipulated to serve as a potent delivery system for targeted cancer therapy. EVs can be engineered or modified to improve their ability to target tumors and deliver therapeutic substances, such as chemotherapeutic drugs, nucleic acids, and proteins, for the treatment of cancer. This review provides an overview of the biogenesis and recycling of EVs, discusses their roles in cancer development, and highlights their potential as a delivery system for targeted cancer therapy.
Telehealth Engaged Music for Pain Outcomes: A Music and Imagery Proof-of-concept Study with Veterans
Authors: Story Kristin M , Robb Sheri L , Bravata Dawn M , Damush Teresa M , Bair Matthew J
Published: May 2024

Music therapy interventions target biopsychosocial outcomes and are a non-pharmacological option for integrated pain management. To date, most music and pain studies have focused on acute pain, passive music experiences, and in-person delivery. The purpose of this study was to examine feasibility and acceptability and determine proof-of-concept for a newly developed telehealth music imagery (MI) intervention for Veterans with chronic pain. A single-group proof-of-concept pilot study was conducted with Veterans with chronic pain (n = 8). Feasibility was assessed through examination of recruitment, retention, and session/measure completion rates; acceptability through participant interviews; and whether the intervention resulted in clinically meaningful change scores (pre- to post-intervention) on measures of pain, anxiety, and depression at the individual level. For Veterans who passed eligibility screening, we had an enrollment rate of 89%, with good retention (75%). Overall, participating Veterans found the intervention acceptable, identified specific challenges with technology, and recommended an increased number of sessions. Preliminary outcome data for pain, anxiety, and depression were mixed, with some Veterans reporting clinically meaningful improvements and others reporting no change or worsening symptoms. Findings informed modifications to the telehealth MI intervention and the design of a larger pilot randomized controlled trial to assess feasibility and acceptability of the modified intervention in a larger population of Veterans with chronic pain using additional measures and a control condition.
The importance of early recognition of extraintestinal manifestations of digestive tract dysfunction following gastrointestinal surgery
Authors: Pang Michelle , Kuwada Scott
Published: May 2024

We report a case of a 47-year-old male who presented with altered mental status. A review of his records revealed a weight loss of 20 lbs over the past 6 years, a recent hospitalization for idiopathic polyneuropathy with failure to thrive, and prior surgeries for peptic ulcer disease and small bowel obstruction. He was alert but had retrograde amnesia and peripheral neuropathy. A diagnosis was made, and the patient improved with treatment but was unfortunately left with irreversible neurological deficits. We discuss the importance of recognizing the extraintestinal manifestations of gastrointestinal dysfunction following gastrointestinal surgery.
To Calm and to Commend: Veterans’ Musical Preferences Anticipating End of Life
Authors: Krauss Beatrice J
Published: May 2024

Introduction

Since World War 1, physicians have noted the calming effects of music for military personnel experiencing “shell shock,” Post Traumatic Stress Disorder (PTSD), or stress. Researchers have documented that stress or PTSD-like symptoms re-emerge for veterans at the end of life, triggered by hospital-like settings, co-occurring conditions, and debilitation. Dying veterans also face integration of their service and combat experiences into summations of their lives. In response, there has been a national movement for bedside ceremonies, often with music, to honor veterans.

Materials and Methods

The project elicited veterans’ musical preferences for calming and for music for honor services, using non-hospitalized veterans as surrogates for veterans in hospice. Respondent-driven sampling protected confidentiality and likely resulted in participants being representative of US veterans in terms of ethnicity, gender, and military branch. Recruitment materials contained all elements of informed consent, with consent collected in the introduction to the online survey. The survey had embedded links to musical performances, as well as write-in musical choices, and allowed US veterans from the Army, Air Force, Marines, and Navy to note their preferences both for music that was calming and music to be used in honor ceremonies. Online queries also asked about stress during service, usual coping strategies for stress, and current or past symptoms of PTSD. Links to hot lines were provided. The study was approved by the University of Arizona Institutional Review Board.

Results

Listening to music was the most prevalent of the 20 coping mechanisms for stress in this sample of 30 veterans. Musical preferences were stable across age groups. For calming, music at resting heartbeat rhythms was chosen. Music from early adulthood or from the timelessness of the classics was selected most often. Modern music with lyrics has themes of duty, affirmation, gratitude, and relief. The nearly universal soothing effects of lullabies were recognized. For music for honor ceremonies, desires were often independent of the military branch. Patriotic songs, or songs recognizing multiple service branches, or with themes of peace and affirmation were more often chosen than music from a particular service branch.

Conclusion

Listening to music is a frequent coping strategy for veterans. While themes representing classical music choices are readily available in anthologies, other music chosen by this sample is not; the veterans’ preferred music is rarely found in compilations of popular, movie, and TV music. Hospice and hospital intakes that document and communicate veterans’ musical preferences to music therapists and therapeutic musicians may better support service men and women. Further research may examine veterans’ preference for live or recorded music at end of life given the importance of meaning-making and the presence of others documented in the literature.
Cluster cosmology redux: a compact representation for the halo mass function
Authors: Norton Cameron E , Adams Fred C , Evrard August E
Published: May 2024

Groups and clusters of galaxies imprint coherent, arcminute-scale features across the spectrophotometric sky, especially optical-IR clusters of galaxies, spectral distortions in the cosmic microwave background, and extended sources of X-ray emission. The space–time density of the host dark matter halo population – the halo mass function (HMF) – is a common theoretical basis for modelling such observable features. We explore a compact representation – a dual-quadratic (DQ-HMF) form – that features readily interpretable parameters representing polynomial expansions of the space–time number density surface, first in terms of log-mass, then in redshift. The DQ-HMF form fits Mira-Titan N-body emulator expectations for halo masses $10^{13.7-14.5} \, h^{-1}\, {\rm M}_\odot$ over redshifts, 0.1 < z < 1.5 to within $\sim \! 5~{{\ \rm per\ cent}}$. We provide best-fitting parameters for a Planck 2018 cosmology and demonstrate model self-similarity in the Ωm−$\, \sigma _8$ plane. Convolving with a minimal mass–observable relation (MOR) yields closed-form expressions for counts, mean mass, and mass variance of cluster samples characterized by an observable property. Performing information-matrix forecasts of potential parameter constraints from existing and future surveys, we demonstrate the potential for percent-level constraints on model parameters by an LSST-like optical cluster survey of 300 000 clusters and a richness–mass variance of 0.32. Even better constraints could potentially be achieved by a survey with one-tenth the sample size but with a reduced selection property variance of 0.12. Potential benefits and extensions to the basic MOR parametrization are discussed.
Increasing AGN sample completeness using long-term near-infrared variability
Authors: Green K , Elmer E , Maltby D T , Almaini O , Merrifield M , Hartley W G
Published: May 2024

In this work, we use 8 years of deep near-infrared imaging to select and study a new set of 601 active galaxies identified through long-term near-infrared (NIR) variability in the UKIDSS Ultra Deep Survey (UDS). These objects are compared to 710 X-ray bright Active Galactic Nuclei (AGN) detected by the Chandra X-ray observatory. We show that infrared variability and X-ray emission select distinct sets of active galaxies, finding only a 37 per cent overlap of galaxies detected by both techniques and confirming NIR-variable AGN to be typically X-ray quiet. Examining the mass functions of the active galaxies shows that NIR variability detects AGN activity in galaxies over a significantly wider range of host stellar mass compared to X-ray detection. For example, at z ∼ 1, variable AGN are identified among approximately 1 per cent of galaxies in a roughly flat distribution above the stellar mass completeness limit ($\gt 10^{9}\rm \, {\rm M}_{\odot }$), while X-ray detection primarily identifies AGN in galaxies of higher mass ($\gt 10^{10}\rm \, {\rm M}_{\odot }$). We conclude that long-term near-infrared variability provides an important new tool for obtaining more complete samples of AGN in deep survey fields.
HYMALAIA: a hybrid lagrangian model for intrinsic alignments
Authors: Maion Francisco , Angulo Raul E , Bakx Thomas , Chisari Nora Elisa , Kurita Toshiki , Pellejero-Ibáñez Marcos
Published: May 2024

The intrinsic alignment of galaxies is an important ingredient for modelling weak-lensing measurements, and a potentially valuable cosmological and astrophysical signal. In this paper, we present HYbrid Model Advected from LAgrangian space for IA (HYMALAIA): a new model to predict the intrinsic alignments of biased tracers. HYMALAIA is based on a perturbative expansion of the statistics of the Lagrangian shapes of objects, which is then advected to Eulerian space using the fully non-linear displacement field obtained from N-body simulations. We demonstrate that HYMALAIA is capable of consistently describing monopole and quadrupole of halo shape–shape and matter–shape correlators, and that, without increasing the number of free parameters, it does so more accurately than other perturbatively inspired models such as the non-linear alignment model and the tidal-alignment-tidal-torquing model.
Structure of an internal loop motif with three consecutive U•U mismatches from stem–loop 1 in the 3′-UTR of the SARS-CoV-2 genomic RNA
Authors: Vögele Jennifer , Duchardt-Ferner Elke , Bains Jasleen Kaur , Knezic Bozana , Wacker Anna , Sich Christian , Weigand Julia E , Šponer Jiří , Schwalbe Harald , Krepl Miroslav , Wöhnert Jens
Published: May 2024

The single-stranded RNA genome of SARS-CoV-2 is highly structured. Numerous helical stem–loop structures interrupted by mismatch motifs are present in the functionally important 5′- and 3′-UTRs. These mismatches modulate local helical geometries and feature unusual arrays of hydrogen bonding donor and acceptor groups. However, their conformational and dynamical properties cannot be directly inferred from chemical probing and are difficult to predict theoretically. A mismatch motif (SL1-motif) consisting of three consecutive U•U base pairs is located in stem–loop 1 of the 3′-UTR. We combined NMR-spectroscopy and MD-simulations to investigate its structure and dynamics. All three U•U base pairs feature two direct hydrogen bonds and are as stable as Watson–Crick A:U base pairs. Plasmodium falciparum 25S rRNA contains a triple U•U mismatch motif (Pf-motif) differing from SL1-motif only with respect to the orientation of the two closing base pairs. Interestingly, while the geometry of the outer two U•U mismatches was identical in both motifs the preferred orientation of the central U•U mismatch was different. MD simulations and potassium ion titrations revealed that the potassium ion-binding mode to the major groove is connected to the different preferred geometries of the central base pair in the two motifs.
Protein phosphatase PP1 regulation of RNA polymerase II transcription termination and allelic exclusion of VSG genes in trypanosomes
Authors: Kieft Rudo , Zhang Yang , Yan Haidong , Schmitz Robert J , Sabatini Robert
Published: May 2024

The genomes of Leishmania and trypanosomes are organized into polycistronic transcription units flanked by a modified DNA base J involved in promoting RNA polymerase II (Pol II) termination. We recently characterized a Leishmania complex containing a J-binding protein, PP1 protein phosphatase 1, and PP1 regulatory protein (PNUTS) that controls transcription termination potentially via dephosphorylation of Pol II by PP1. While T. brucei contains eight PP1 isoforms, none purified with the PNUTS complex, complicating the analysis of PP1 function in termination. We now demonstrate that the PP1-binding motif of TbPNUTS is required for function in termination in vivo and that TbPP1-1 modulates Pol II termination in T. brucei and dephosphorylation of the large subunit of Pol II. PP1-1 knock-down results in increased cellular levels of phosphorylated RPB1 accompanied by readthrough transcription and aberrant transcription of the chromosome by Pol II, including Pol I transcribed loci that are typically silent, such as telomeric VSG expression sites involved in antigenic variation. These results provide important insights into the mechanism underlying Pol II transcription termination in primitive eukaryotes that rely on polycistronic transcription and maintain allelic exclusion of VSG genes.
The p21CIP1-CDK4-DREAM axis is a master regulator of genotoxic stress-induced cellular senescence
Authors: Schmidt Ariane , Allmann Sebastian , Schwarzenbach Christian , Snyder Petra , Chen Jia-Xuan , Nagel Georg , Schöneis Anna , Rasenberger Birgit , Beli Petra , Loewer Alexander , Hofmann Thomas G , Tomicic Maja T , Christmann Markus
Published: May 2024

Cellular senescence, a major driver of aging, can be stimulated by DNA damage, and is counteracted by the DNA repair machinery. Here we show that in p16INK4a-deficient cells, senescence induction by the environmental genotoxin B[a]P or ionizing radiation (IR) completely depends on p21CIP1. Immunoprecipitation-based mass spectrometry interactomics data revealed that during senescence induction and maintenance, p21CIP1 specifically inhibits CDK4 and thereby activates the DREAM complex. Genome-wide transcriptomics revealed striking similarities in the response induced by B[a]P and IR. Among the top 100 repressed genes 78 were identical between B[a]P and IR and 76 were DREAM targets. The DREAM complex transcriptionally silences the main proliferation-associated transcription factors E2F1, FOXM1 and B-Myb as well as multiple DNA repair factors. Knockdown of p21CIP1, E2F4 or E2F5 diminished both, repression of these factors and senescence. The transcriptional profiles evoked by B[a]P and IR largely overlapped with the profile induced by pharmacological CDK4 inhibition, further illustrating the role of CDK4 inhibition in genotoxic stress-induced senescence. Moreover, data obtained by live-cell time-lapse microscopy suggest the inhibition of CDK4 by p21CIP1 is especially important for arresting cells which slip through mitosis. Overall, we identified the p21CIP1/CDK4/DREAM axis as a master regulator of genotoxic stress-induced senescence.
Trends and socioeconomic inequality of the burden of congenital abnormalities of the kidney and urinary tract among children and adolescents
Authors: He Guohua , Liu Yunfei , Bagga Arvind , Onubogu Chinyere Ukamaka , Schaefer Franz , Zou Zhiyong , Smoyer William E , Xiao Nianzhou , Lin Tianxin , Lanewala Ali Asghar , Kang Hee Gyung , Waheed Muhammad Zeeshan , Park Seungkyo , Jiang Xiaoyun , Song Yi , Ding Jie
Published: May 2024

Background

Although congenital abnormalities of the kidney and urinary tract (CAKUT) is the leading cause of childhood-onset chronic kidney disease and kidney failure, comprehensive information on the disease burden among children and adolescents globally is lacking. We aim to report the trends and socioeconomic inequality of CAKUT burden for people aged 0–24 years from 1990 to 2019.

Methods

We reported the prevalence, mortality and disability-adjusted life-years (DALYs) for CAKUT based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, quantified the association of disease burden and socio-demographic index (SDI), and calculated the slope index of inequality, the relative index of inequality and concentration index.

Results

In 2019, the global prevalence, mortality and DALYs of CAKUT among individuals aged 0–24 years were 167.11 (95% confidence interval 166.97, 167.25), 0.30 (0.29, 0.30) and 32.22 (32.16, 32.29), respectively, per 100 000 population. The greatest prevalence, mortality and DALYs were recorded in the 0–4 years age group. The greatest mortality and DALYs were recorded in low SDI countries and territories. During 1990 to 2019, the prevalence, mortality and DALYs decreased globally, while in low and low-middle countries and territories the reduction was much less slower. India, Nigeria and Pakistan had the highest DALYs. Saudi Arabia and China exhibited a markedly decrease of CAKUT burden. Globally for every 0.1 increase in SDI, there was a 20.53% reduction in mortality and a 16.31% decrease in DALYs, but a 0.38% rise in prevalence.

Conclusions

Inequality for disease burden of varying SDI was increasing globally. Thus, specific preventive and health service measures are needed to reduce the global burden from CAKUT.
Genomic ascertainment of primary central nervous system cancers in adolescents and young adults
Authors: Stewart Douglas R
Published: May 2024

Genomic ascertainment is the inversion of the traditional phenotype-first approach; with a “genome-first” approach, a cohort linked to electronic health records (EHR) undergoes germline sequencing (array, panel, exome, and genome) and deleterious variation of interest in a gene (or set of genes) are identified. Phenotype is then queried from the linked EHR and from call-back investigation and estimates of variant prevalence, disease penetrance, and phenotype can be determined. This should permit a better estimate of the full phenotypic spectrum, severity, and penetrance linked to a deleterious variant. For now, given the modest size, limited EHR, and age of participants in sequenced cohorts, genomic ascertainment approaches to investigate cancer in children and young adults will likely be restricted to descriptive studies and complement traditional phenotype-first work. Another issue is the ascertainment of the cohort itself: Participants need to survive long enough to enroll. Not accounting for this may lead to bias and incorrect estimates of variant prevalence. Adult-focused cohorts with EHR extending back into childhood, linked to cancer registries, and/or studies that permit recontact with participants may facilitate genomic ascertainment in pediatric cancer research. In summary, genomic ascertainment in pediatric primary brain cancer research remains largely untapped and merits further investigation.
No drug holidays in BRAFV600E glioma patients: An argument for dose reduction of targeted therapies
Authors: Bazer Danielle A , Kolchinski Anna , Bush Nancy A O , Clarke Jennifer L , Bagley Stephen J , Schreck Karisa C
Published: May 2024

Background

Combined BRAF and MEK inhibition is effective for some BRAFV600E-altered gliomas, a cancer for which there are few effective therapies. While recent clinical trials demonstrate objective response rates of 30%–40%, tolerable adverse event rates are 70%–90%, and 12%–15% of patients stop therapy for toxicity. There are no clear guidelines regarding the timing and reinitiation of BRAF-targeted therapies following drug holidays. Here, we describe 4 patients with rapid disease progression during periods of treatment interruption. All patients experienced a response upon resumption of targeted therapy.

Methods

This is a multi-institutional, retrospective review of 4 patients.

Results

Three patients were diagnosed with BRAFV600E mutated anaplastic pleomorphic xanthoastrocytoma (aPXA) and 1 with epithelioid glioblastoma. The age range was 32 to 46; 3 patients were female and one patient was male. All patients were initially treated with radiation and were subsequently treated with BRAF/MEK inhibitors after disease progression. All patients with aPXA required the targeted therapy to be held due to toxicity and 1 patient held the therapy prior to transitioning to a novel BRAF-targeted agent. All patients were restarted on BRAF/MEK inhibitors after a drug holiday. Three patients required a dose reduction and all improved clinically following reinitiation.

Conclusions

Clinical and radiographic progression may occur rapidly upon holding BRAF-targeted therapy, warranting judicious dose reductions and minimization of drug holidays.
Xuemei Chen: Original innovation often derives from free exploration
Authors: Gu Chao
Published: May 2024

Xuemei Chen is a distinguished biologist. She was elected a member of the US National Academy of Sciences in 2013, and is now the Dean of the School of Life Sciences at Peking University. Her main research areas are flower development, plant microRNAs, and RNA modifications. In this interview, Xuemei Chen discussed the prospects of plant research, and emphasized the significance of free exploration to achieve the ground-breaking ‘0 to 1’ innovation—until free exploration leads to the discovery of the ‘1’, one may not know what the ‘0’ is and may not be able to intentionally seek it. She also introduced the upcoming Beijing Advanced Center of RNA Biology (BEACON), and expressed her views on organized scientific research.
Cabotegravir + Rilpivirine Long-Acting: Overview of Injection Guidance, Injection Site Reactions, and Best Practices for Intramuscular Injection Administration
Authors: Teichner Paula , Chamay Nadine , Elliot Emilie , Pascual-Bernáldez Miguel , Merrill Deanna , Garris Cindy , D’Amico Ronald , Felizarta Cecy , Torres Emma , Van Solingen-Ristea Rodica , Baugh Bryan , Patel Parul , Vannappagari Vani , Dakhia Samia , Polli Joseph W , Garside Louise , Grove Richard , Thiagarajah Shanker , Birmingham Eileen , van Wyk Jean
Published: May 2024

Background

Cabotegravir (CAB) + rilpivirine (RPV) dosed monthly or every 2 months is a complete long-acting (LA) regimen for the maintenance of human immunodeficiency virus type 1 virologic suppression. Across the phase 3/3b trials, the most frequently reported adverse events were injection site reactions (ISRs).

Methods

We present pooled ISR characteristics and outcomes for participants receiving CAB + RPV LA through week 96 of the FLAIR and ATLAS-2M studies, and survey results from healthcare providers (HCPs) giving injections (eg, injectors) in the ATLAS, FLAIR, and ATLAS-2M studies to determine optimal injection techniques. Surveys were anonymous, self-administered online questionnaires that queried provider demographics, injection experience, and techniques to minimize pre-/postinjection discomfort. Data were summarized using descriptive statistics.

Results

Overall, 8453 ISRs were reported by 801 participants receiving ≥1 injection of CAB LA/RPV LA. Most ISRs were mild to moderate in severity (grade 1–2, 99%), with a median duration of 3 days (interquartile range, 2–4 days), and rarely led to withdrawal (2%). Surveys were completed by 181 HCPs across 113 sites. Pushing the intramuscular injection at slow speed (66%), bringing the medication to room temperature (58%), and relaxing the gluteus muscle before injecting (53%) were ranked as effective preinjection/injection procedure practices for minimizing pain. Most injectors (60%) indicated that a prone position provided optimal patient comfort, and 41% had no preference on injection medication order.

Conclusions

Taken together, the data demonstrate favorable tolerability with CAB + RPV LA injections over the long term and simple techniques routinely used by injectors to help optimize the administration of CAB + RPV LA injections.
Varicella-Zoster Virus–Induced Neurologic Disease After COVID-19 Vaccination: A Multicenter Observational Cohort Study
Authors: Elbaz Meital , Hoffman Tomer , Yahav Dafna , Dovrat Sarah , Ghanem-Zoubi Nesrin , Atamna Alaa , Grupel Daniel , Reisfeld Sharon , Hershman-Sarafov Mirit , Ciobotaro Pnina , Najjar-Debbiny Ronza , Brosh-Nissimov Tal , Chazan Bibiana , Yossepowitch Orit , Wiener-Well Yonit , Halutz Ora , Reich Shelley , Ben-Ami Ronen , Paran Yael
Published: May 2024

Background

Early reports described an increased risk of herpes zoster following receipt of mRNA-based COVID-19 vaccines. The objective was to assess whether COVID-19 vaccine is associated with varicella-zoster virus–induced neurologic disease (VZV-ND).

Methods

This multicenter retrospective case-control study with a test-negative design was conducted at 12 hospitals in Israel. We included all patients admitted with VZV-ND between January 2020 and December 2021 and matched controls with a negative polymerase chain reaction result for VZV in cerebrospinal fluid.

Results

We identified 188 patients meeting the case definition of VZV-ND who were admitted during the study period. Cases were matched with 376 controls. There was no significant variation in the incidence of VZV-ND between 1 year preceding and 1 year following the deployment of BNT162b2 in Israel. Analysis of persons who had received at least 1 dose of COVID-19 vaccine (n = 259) showed similar proportions of VZV-ND and non–VZV-ND in 4 intervals (30, 42, 50, 60 days) following the last vaccine dose. The median time from the last vaccine dose to hospitalization with a neurologic syndrome was 53 days (IQR, 25–128) and 82 days (IQR, 36–132) for VZV-ND and non–VZV-ND, respectively, not reaching statistical significance (P = .056). The rate of VZV-ND in vaccinated patients was no different from the rate in the unvaccinated group (30.9% vs 35.4%, P = .2).

Conclusions

We did not find an association between COVID-19 vaccine and VZV-ND. Since COVID-19 vaccine is now recommended yearly, every fall and winter, establishing the safety of the vaccine is of great importance.
Review of the In Vitro Microbiological Activity of Mecillinam Against Common Uropathogens in Uncomplicated Urinary Tract Infection: Focus on Resistant Pathogens
Authors: Lodise Thomas P , Kaye Keith S , Santerre Henriksen Anne , Kahlmeter Gunnar
Published: May 2024

Antimicrobial resistance in uropathogens commonly causing urinary tract infections (UTIs) is a growing problem internationally. Pivmecillinam, the oral prodrug of mecillinam, has been used for over 40 years, primarily in Northern Europe and Canada. It is recommended in several countries as a first-line agent for the treatment of uncomplicated UTIs (uUTIs) and is now approved in the United States. We performed a structured literature search to review the available evidence on susceptibility of common uUTI-causing uropathogens to mecillinam. Among 38 studies included in this literature review, susceptibility rates for Escherichia coli to mecillinam—including resistant phenotypes such as extended-spectrum β-lactamase–producing E. coli—exceed 90% in most studies. High rates of susceptibility were also reported among many other uropathogens including Klebsiella spp., Enterobacter spp., and Citrobacter spp. In the current prescribing climate within the United States, pivmecillinam represents a viable first-line treatment option for patients with uUTI.
Deep Sternal Wound Infection Caused by Rhizopus Species After Coronary Artery Bypass Graft
Authors: Cunningham Cody A , Grys Thomas E , Downey Francis X , Saling Christopher F , Orenstein Robert , Blair Janis E
Published: May 2024

Deep sternal wound infection is a rare complication of cardiac surgery that is typically caused by skin resident flora, such as species of Staphylococcus and Streptococcus. Infections caused by fungi are less common and are generally caused by Candida species. Regardless of etiology, these infections are associated with significant morbidity and mortality. We present a case of postoperative mediastinitis that occurred following a 5-vessel coronary artery bypass graft and was caused by a filamentous fungus of the Rhizopus genus. The patient was treated with serial debridement, liposomal amphotericin B, and isavuconazonium and was discharged from the hospital in stable condition. Fungal mediastinitis is a rare entity, and clinicians must maintain a high level of suspicion to make the diagnosis. A fungal cause of postoperative mediastinitis should be considered in patients with negative bacterial cultures, uncontrolled diabetes, or current immunosuppression or those who present weeks after surgery with a subacute onset of symptoms.
Modulation of marble-burying behavior in adult versus adolescent C57BL/6J mice of both sexes by ethologically relevant chemosensory stimuli
Authors: Jimenez Chavez C Leonardo , Szumlinski Karen K
Published: May 2024

The marble-burying test is a pharmacologically validated paradigm used to study anxiety-like behaviors in laboratory rodents. Our laboratory has employed this assay as part of a behavioral screen to examine drug-induced negative affective states. Historically, the majority of our prior binge alcohol-drinking studies employed male subjects exclusively and reliably detected adolescent-adult differences in both basal and alcohol withdrawal-induced negative affect. However, age-related differences in marble-burying behavior were either absent or opposite those observed in our prior work when female subjects were included in the experimental design. As chemosensory cues from females are reported to be anxiolytic in males, the present study examined how odors from adult members of the opposite and same sex (obtained from soiled bedding) influence marble-burying behavior in adult, as well as adolescent, mice. Control studies examined the responsiveness of mice in the presence of novel neutral (vanilla) and aversive (tea tree) odors. Adult males exhibited reduced signs of anxiety-like behavior in the presence of female-soiled bedding, while adult females and adolescent mice of both sexes increased marble-burying behavior in the presence of both male- and female-soiled bedding. All mice exhibited increased burying in the presence of an aversive odor, while only adolescents increased marble-burying in response to the novel neutral odor. These data indicate sex by age interactions in the effects of volatile and nonvolatile odors from sexually-naive adult conspecifics on indices of anxiety-like behavior in the marble-burying test of relevance to the experimental design and procedural timing of experiments including sex as a biological variable.
Cerenkov luminescence imaging and flexible autoradiography for specimen margin assessment during breast-conserving cancer surgery
Authors: Sinha Aaditya , Peterson Zhane , Shifa Belul , Jeffery Hannah , Jurrius Patriek , Allen Sarah , Lee Eugene , Azmat Mohammed , Barrass Rachel , Bailey Damion , Johnson Jessica , Adamson Kathryn , Karydakis Vasileios , Shaari Elina , Thorat Mangesh , Hamed Hisham , Bitsakou Georgina , Pinder Sarah , Menon Padma , Ng Wen , Cook Gary , Joemon John , Jacob Armidita , Pereira Sofia , Thomas Jocelyn , Begum Ruheana , El-Boghdadly Karim , Van Hemelrijck Mieke , Kothari Ashutosh , Purushotham Arnie
Published: May 2024

Background

Among women with breast cancer who undergo breast-conserving surgery (BCS), 20% to 25% require further surgery because of close or involved margins. Improved techniques are needed to assess resection margins.

Purpose

The study aims were to assess the feasibility of the combined techniques of Cerenkov luminescence imaging–flexible autoradiography (CLI-FAR) to assess excision specimen margins in women undergoing BCS and to determine the diagnostic performance of intraoperative CLI-FAR imaging with postoperative histopathology as the reference standard.

Materials and Methods

Women undergoing BCS were recruited prospectively at a single center over 13 months. Patients were injected with 250 MBq ± 10 MBq of 18F-fluorodeoxyglucose, 145 minutes before surgery; the excised specimens were imaged intraoperatively. The surgically excised tumor was initially imaged using conventional x-ray, and margins suspected to be involved by tumor were then imaged using CLI-FAR. CLI-FAR imaging was performed using the LightPath system (Lightpoint), an in vitro diagnostic device designed to identify and locate positron-emitting radionuclides. Any suspicious margin underwent an immediate reexcision in the form of cavity shavings. Sensitivity, specificity, and positive and negative predictive values while considering histopathological assessment as the golden standard were used to assess the performance of CLI-FAR.

Results

In all, 54 specimens were imaged in 52 patients, with a total of 104 margins reviewed using CLI-FAR. The results showed a specificity of 97.8% (89/91; 95% confidence interval [CI], 95.0-100.6), sensitivity of 76.9% (10/13; 95% CI, 68.3-85.0), positive predictive value of 83.3% (10/12; 95% CI, 76.2-90.5), and negative predictive value of 96.7% (89/92; 95% CI, 93.3-100.2). In all, 8 patients had 10 positive margins on CLI-FAR imaging and were treated accordingly. CLI-FAR imaging reduced the reexcision rate by 69% (17.3/25).

Conclusion

CLI-FAR imaging is a promising technique for intraoperative margin assessment in women undergoing BCS for invasive breast cancer.
Disease-specific definitions of new bone formation on spine radiographs: a systematic literature review
Authors: Gazel Ummugulsum , Ayan Gizem , Hryciw Nicole , Delorme Jean-Philippe , Hepworth Elliot , Sampaio Marcos , Jibri Zaid , Karsh Jacob , Aydin Sibel Zehra
Published: May 2024

Objectives

We aimed to explore the radiographic definitions of types of New Bone formation (NBF) by focusing on the terminology, description and location of the findings.

Methods

Three systematic literature reviews were conducted in parallel to identify the radiographic spinal NBF definitions for spondyloarthritis (SpA), Diffuse Idiopathic Skeletal Hyperostosis (DISH) and Osteorathritis (OA). Study characteristics and definitions were extracted independently by two reviewers. Definitions were analysed and collated based on whether they were unique, modified or established from previous research.

Results

We identified 33 studies that indicated a definition for the NBF in SpA, 10 for DISH and 7 for spinal OA. In SpA, the variations in syndesmophytes included the description as well as the subtypes and locations. The differentiation of syndesmophytes from osteophytes were included in 12 articles, based on the origin and the angle of the NBF and associated findings. The definitions of DISH varied in the number of vertebrae, level and laterality. For OA, five articles indicated that osteophytes arose from the anterior or lateral aspects of the vertebral bodies, and two studies required a size cut-off.

Discussion

Our ultimate aim is to create formal NBF definitions for SpA, DISH and OA guided by an atlas, through a Delphi exercise with international experts. The improved ability to differentiate these conditions radiographically will not only allow the clinicians to accurately approach patients but also will help the researchers to better classify patient phenotypes and focus on accurate radiographic outcomes.
Promoting cell proliferation and collagen production with ascorbic acid 2-phosphate-releasing poly(l-lactide-co-ε-caprolactone) membranes for treating pelvic organ prolapse
Authors: Kurki Alma , Paakinaho Kaarlo , Hannula Markus , Karjalainen Sanna , Kuismanen Kirsi , Hyttinen Jari , Miettinen Susanna , Sartoneva Reetta
Published: May 2024

Pelvic organ prolapse (POP) afflicts millions of women globally. In POP, the weakened support of the pelvic floor results in the descent of pelvic organs into the vagina, causing a feeling of bulging, problems in urination, defaecation and/or sexual function. However, the existing surgical repair methods for relapsed POP remain insufficient, highlighting the urgent need for more effective alternatives. Collagen is an essential component in pelvic floor tissues, providing structural support, and its production is controlled by ascorbic acid. Therefore, we investigated novel ascorbic acid 2-phosphate (A2P)-releasing poly(l-lactide-co-ε-caprolactone) (PLCLA2P) membranes in vitro to promote cell proliferation and extracellular matrix protein production to strengthen the natural support of the pelvic fascia for POP applications. We analysed the mechanical properties and the impact of PLCLA2P on cellular responses through cell culture analysis using human vaginal fibroblasts (hVFs) and human adipose-derived stem/stromal cells (hASCs) compared to PLCL. In addition, the A2P release from PLCLA2P membranes was assessed in vitro. The PLCLA2P demonstrated slightly lower tensile strength (2.2 ± 0.4 MPa) compared to PLCL (3.7 ± 0.6 MPa) for the first 4 weeks in vitro. The A2P was most rapidly released during the first 48 h of in vitro incubation. Our findings demonstrated significantly increased proliferation and collagen production of both hVFs and hASCs on A2P-releasing PLCLA2P compared to PLCL. In addition, extracellular collagen Type I fibres were detected in hVFs, suggesting enhanced collagen maturation on PLCLA2P. Moreover, increased extracellular matrix protein expression was detected on PLCLA2P in both hVFs and hASCs compared to plain PLCL. In conclusion, these findings highlight the potential of PLCLA2P as a promising candidate for promoting tissue regeneration in applications aimed for POP tissue engineering applications.
Effects of supplemental methionine sources in finishing pig diets on growth performance, carcass characteristics, cutting yields, and meat quality
Authors: Remole Hannah M , Htoo John K , Mendoza S M , Bradley Casey L , Dilger Ryan N , Dilger Anna C , Harsh Bailey N
Published: May 2024

Supplemental methionine (Met) is widely used within the swine industry; however, data are limited regarding the effect of Met sources on carcass cutability and meat quality. The objective was to determine the effects of L-Met (LM, 99%), DL-Met (DLM, 99%), or calcium salt of DL-Met hydroxyl analog (MHA, 84%) in finishing pig diets on carcass characteristics and meat quality. At 9 weeks of age, pigs (N = 240) were allocated to 60 single-sex pens for a four-phase finishing trial that lasted 104 d. Pigs were fed a common grower diet until day 56 where pens were randomly allotted to one of the three experimental diets. For the remaining 7 wk of the finisher phase, pigs (BW = 79.9 ± 0.80 kg) were fed diets containing LM, DLM, or MHA, with the supplemental Met source providing 25% of standardized ileal digestible (SID) Met + cysteine (Cys) requirement based on 65% bioefficacy for MHA in comparison with LM or DLM. One pig per pen was slaughtered at the study conclusion (on day 104), and the left sides of carcasses were fabricated into subprimal cuts to determine carcass-cutting yields. Loin quality including proximate composition and shear force were measured. Hot carcass weight was not different (P = 0.34) between treatments (LM 104.5 kg; DLM 103.0 kg; MHA 101.5 kg), moreover, loin eye area was not different (P = 0.98) between treatments (LM 52.65 cm²; DLM 52.49 cm²; MHA 52.81 cm²). Boneless carcass-cutting yield was not different (P = 0.56) between treatments (LM 54.97 kg; DLM 54.82 kg; MHA 54.52 kg). Loin pH was not different (P = 0.24) between treatments (LM 5.45; DLM 5.48; MHA 5.45). However, drip loss tended to be reduced (P = 0.11) by the DLM treatment (5.58%) compared with LM (7.03%) and MHA (6.68%) treatments. Shear force was not different (P = 0.85) between treatments (LM 3.03 kg; DLM 3.06 kg; MHA 3.10 kg). However, cook loss tended to be reduced (P = 0.06) by the DLM treatment (16.20%) compared with LM (18.18%) and MHA (18.50%) treatments. These data suggest that only minimal differences in carcass cutability and meat quality can be attributed to Met source in finishing pig diets when using 65% bioefficacy for MHA relative to L-Met or DL-Met.