bluuebunny/crossref_metadata_2025_split huggingface dataset:
Asprosin contributes to vascular remodeling in hypertensive rats via superoxide signaling
Authors: Xu Zhi-Qin , Li Xiu-Zhen , Zhu Rong , Ge Rui , Wei Hui , Shi Hong-Wei , Wang Zhe , Yang Cuan , Yang Ya-Wen , Lu Xue-Juan , Chen Ai-Dong , Zhu Guo-Qing , Tan Xiao 
Published: May 2024

Objective:
Proliferation and migration of vascular smooth muscle cells (VSMCs) contribute to vascular remodeling. Asprosin, a newly discovered protein hormone, is involved in metabolic diseases. Little is known about the roles of asprosin in cardiovascular diseases. This study focused on the role and mechanism of asprosin on VSMC proliferation and migration, and vascular remodeling in a rat model of hypertension.

Methods and results:
VSMCs were obtained from the aortic media of 8-week-old male Wistar–Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Asprosin was upregulated in the VSMCs of SHR. For in vitro studies, asprosin promoted VSMC proliferation and migration of WKY and SHR, and increased Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) activity, NOX1/2/4 protein expressions and superoxide production. Knockdown of asprosin inhibited the proliferation, migration, NOX activity, NOX1/2 expressions and superoxide production in the VSMCs of SHR. The roles of asprosin in promoting VSMC proliferation and migration were not affected by hydrogen peroxide scavenger, but attenuated by superoxide scavenger, selective NOX1 or NOX2 inhibitor. Toll-like receptor 4 (TLR4) was upregulated in SHR, TLR4 knockdown inhibited asprosin overexpression-induced proliferation, migration and oxidative stress in VSMCs of WKY and SHR. Asprosin was upregulated in arteries of SHR, and knockdown of asprosin in vivo not only attenuated oxidative stress and vascular remodeling in aorta and mesentery artery, but also caused a subsequent persistent antihypertensive effect in SHR.

Conclusions:
Asprosin promotes VSMC proliferation and migration via NOX-mediated superoxide production. Inhibition of endogenous asprosin expression attenuates VSMC proliferation and migration, and vascular remodeling of SHR.
Low preoperative serum uric acid is associated with early acute kidney injury after living donor liver transplantation
Authors: Wu Yueh-Tse , Hu Li-Min , Lee Chao-Wei , Lee Wei-Chen , Lin Jr-Rung , Tsai Hsin-I , Yu Huang-Ping 
Published: May 2024

Background:
Liver transplantation is treatment option for patients with end-stage liver disease and hepatocellular carcinoma. Renal function deterioration significantly impacts the survival rates of liver recipients, and serum uric acid (SUA) is associated with both acute and chronic renal function disorders. Thus, our study aimed to assess the relationship and predictive value of preoperative SUA level and postoperative acute kidney injury (AKI) in living donor liver transplantation (LDLT).

Methods:
We conducted a prospective observational study on 87 patients undergoing LDLT. Blood samples were collected immediately before LDLT, and renal function status was followed up for 3 consecutive days postoperatively.

Results:
Low SUA levels (cutoff value 4.15 mg/dL) were associated with a high risk of early posttransplantation AKI. The area under the curve was 0.73 (sensitivity, 79.2%; specificity, 59.4%). Although not statistically significant, there were no deaths in the non-AKI group but two in the early AKI group secondary to liver graft dysfunction in addition to early AKI within the first month after LDLT.

Conclusion:
AKI after liver transplantation may lead to a deterioration of patient status and increased mortality rates. We determined low preoperative SUA levels as a possible risk factor for early postoperative AKI.
Telemedicine for emergency patient rescue
Authors: Subramanian Sanjay , Pamplin Jeremy C. 
Published: May 2024

Purpose of review
This article summarizes recent developments in the application of telemedicine, specifically tele-critical care (TCC), toward enhancing patient care during various types of emergencies and patient rescue scenarios when there are limited resources in terms of staff expertise (i.e., knowledge, skills, and abilities), staffing numbers, space, and supplies due to patient location (e.g., a non-ICU bed, the emergency department, a rural hospital) or patient volume as in pandemic surges.

Recent findings
The COVID-19 pandemic demonstrated the need for rapidly scalable and agile healthcare delivery systems. During the pandemic, clinicians and hospital systems adopted telemedicine for various applications. Taking advantage of technological improvements in cellular networks and personal mobile devices, and despite the limited outcomes literature to support its use, telemedicine was rapidly adopted to address the fundamental challenge of exposure in outpatient settings, emergency departments, patient follow-up, and home-based monitoring. A critical recognition was that the modality of care (e.g., remote vs. in-person) was less important than access to care, regardless of the patient outcomes. This fundamental shift, facilitated by policies that followed emergency declarations, provided an opportunity to maintain and, in many cases, expand and improve clinical practices and hospital systems by bringing expertise to the patient rather than the patient to the expertise. In addition to using telemedicine to maintain patient access to healthcare, TCC was harnessed to provide local clinicians, forced to manage critically ill patients beyond their normal scope of practice or experience, access to remote expertise (physician, nursing, respiratory therapist, pharmacist). These practices supported decades of literature from the telemedicine community describing the effectiveness of telemedicine in improving patient care and the many challenges defining its value.

Summary
In this review, we summarize numerous examples of innovative care delivery systems that have utilized telemedicine, focusing on ‘mobile’ TCC technology solutions to effectively deliver the best care to the patient regardless of patient location. We emphasize how a ‘paradigm of better’ can enhance the entirety of the healthcare system.
177Lu-FAP-2286 Therapy in a Patient With Metastatic Rhabdoid Meningioma
Authors: Wan Zibei , Wang Wei , Chen Yue , Zheng Wenlu , Huang Zhanwen 
Published: May 2024

Abstract
Rhabdoid meningioma is a rare subtype of meningioma and has a poor prognosis. Herein, we reported a patient of rhabdoid meningioma with multiple liver, pancreas, and bone metastases, who received 177Lu-FAP-2286 therapy. After 1 treatment cycle, 68Ga-FAP-2286 PET/CT revealed partial remission of the lesions.
Pediatric Plastic Surgery Under Local Anesthesia
Authors: LaGuardia Jonnby S. , Ali-Khan Safi , LaBarge Dalton , Morrison Clinton 
Published: May 2024

Background
Increasing research has shown that select surgical procedures can be performed in an office-based environment with low complication rates. Within the field of plastic surgery, these findings have mainly been studied in adult populations. However, studies regarding the safety and efficacy of office-based plastic surgery in the pediatric population are lacking. In the present study, we demonstrate that appropriately selected office-based pediatric plastic surgery procedures can be performed under local anesthesia for a variety of common surgical indications with low complication rates.

Methods
A retrospective case series of pediatric plastic surgery patients who underwent in-office procedures under local anesthesia at a single academic institution from September 2014 to June 2020 was performed.

Results
Five hundred nine patients were treated in an office setting for various etiologies over the study period. A total of 48.9% of the patients were male and 51.1% were female. Patient age at time of procedure ranged from 24 days to 17 years of age with a median age of 13 years. A total of 778 lesions were treated. There were 10 total complications (1.29%) over the study period with only one surgical site infection that resolved with antibiotic treatment.

Conclusions
Our work indicates that select pediatric plastic surgery procedures can be performed under local anesthesia with low complication rates.
We Are Not Speaking the Same Language
Authors: Attalla Philopatir , Becker Miriam , Clark Robert Craig , Reid Chris M. , Brazio Philip S. 
Published: May 2024

Introduction

Current Procedural Terminology (CPT) codes provide a uniform language for medical billing, but specific codes have not been assigned for lymphatic reconstruction techniques. The authors hypothesized that inadequate codes would contribute to heterogeneous coding practices and reimbursement challenges, ultimately limiting surgeons' ability to treat patients.

Methods
A 22-item virtual questionnaire was offered to 959 members of the American Society of Reconstructive Microsurgeons to assess the volume of lymphatic reconstruction procedures performed, CPT codes used for each procedure, and challenges related to coding and providing care.

Results
The survey was completed by 66 board-certified/board-eligible plastic surgeons (6.9%), who unanimously agreed that lymphatic surgery is integral to cancer care, with 86.4% indicating that immediate lymphatic reconstruction should be offered after lymphadenectomy. Most performed lymphovenous bypass, immediate lymphatic reconstruction, liposuction, and vascularized lymph node transfer.
Respondents reported that available CPT codes failed to reflect procedural scope. A wide variety of CPT codes was used to report each type of procedure. Insurance coverage problems led to 69.7% of respondents forgoing operations and 32% reducing treatment offerings. Insurance coverage and CPT codes were identified as significant barriers to care by 98.5% and 95.5% of respondents, respectively.

Conclusions
Respondents unanimously agreed on the importance of lymphatic reconstruction in cancer care, and most identified inadequate CPT codes as causing billing issues, which hindered their ability to offer surgical treatment. Appropriate and specific CPT codes are necessary to ensure accuracy and consistency of reporting and ultimately to improve patient access to care.
TAG-FREE GLYCOSYLATED RHMFG-E8 AS A THERAPY FOR ACUTE KIDNEY INJURY
Authors: Zhang Fangming , Ma Gaifeng , Chaung Wayne , Jacob Asha , Brenner Max , Wang Ping 
Published: May 2024

ABSTRACT

Background: Acute kidney injury (AKI) can result from renal ischemia and reperfusion (I/R) and often occurs during surgical procedures in cardiac, liver, kidney transplantation, and trauma-hemorrhage. Milk fat globule epidermal growth factor-factor VIII (MFG-E8) functions as a bridging molecule to promote the removal of dying cells by professional phagocytes. Because MFG-E8 promotes clearance of apoptotic cells, we have explored its therapeutic potential in various organ injury conditions. To develop human MFG-E8 as a potential therapy, we have generated a human cell-expressed, and thus glycosylated, tag-free recombinant human (rh) MFG-E8 and tested its safety and biological activity in vitro. We hypothesize that the tag-free glycosylated rhMFG-E8 is protective in I/R-induced AKI and it can be developed as an effective therapy for AKI. Methods: To assess the pharmacokinetic properties of the tag-free rhMFG-E8, Sprague-Dawley rats were either untreated or treated with a bolus dose of the tag-free rhMFG-E8, blood collected at various time points and the recovery of human MFG-E8 in the blood were measured by ELISA. Adult male C57BL6 mice underwent bilateral renal ischemia for 30 min, and immediately upon reperfusion, mice were treated intraperitoneally with either normal saline (vehicle) or 20 μg/kg human cell expressed, glycosylated tag-free rhMFG-E8. At either 24 h or 48 h after I/R, blood and kidneys were harvested for further analysis. In separate cohorts of mice after I/R and treatment, mice were observed for 10 days, and survival recorded. Results: AKI rats treated with the tag-free rhMFG-E8 had similar half-life as those in the treated control rats. At 48 h after I/R-induced AKI, renal function markers, blood urea nitrogen, and creatinine were increased and treatment with the tag-free rhMFG-E8 significantly decreased these markers. At both 24 h and 48 h after AKI, inflammatory cytokines, TNF-α, IL-6, and IL-1β were increased and treatment decreased these levels. The kidney mRNA expressions of these cytokines were also increased at 24 h after AKI and treatment significantly decreased those mRNA expressions. Histologically, at 48 h after AKI, tubular damage, and the number of TUNEL staining cells were increased and treatment markedly decreased these measurements. Administration of tag-free rhMFG-E8 at the time of reperfusion improved survival in a 10-day survival study. Conclusion: Our new human cell-expressed tag-free rhMFG-E8 is protective in I/R-induced AKI and it may have the potential to be further developed as a safe and effective therapy for AKI.
Chemoresistance to additive PARP/PI3K dual inhibition in triple-negative breast cancer cell lines is associated with adaptive stem cell-like prevalence
Authors: Petrella Paula E. , Chen Jason W. , Ravelo Gabrielle O. , Cosgrove Benjamin D. 
Published: May 2024

AbstractCancer stem-like cells (CSCs) are posited to exhibit specialized oncogenic capacity to drive malignancies. CSCs are distinguished by enhanced hallmarks of cancer, including apoptosis avoidance, phenotypic plasticity and aberrant growth pathway signaling. Standard-of-care chemotherapies targeted to rapidly cycling cells routinely fail to eliminate this resistant subpopulation, leading to disease recurrence and metastasis. Triple-negative breast cancer (TNBC), a highly aggressive subtype of breast cancer, is enriched for tumor-propagating CD44+/CD24−/lowCSCs, which are poorly ablated by chemotherapeutics and are associated with poor prognosis. CD44 governs sustained PI3K signaling in breast cancer, which is essential for CSC maintenance. PI3K inhibition can elicit DNA damage and down-regulate BRCA1 expression, which in turn enhance the synthetic lethality of PARP inhibitors. Here, we examined a dual chemotherapeutic approach targeting these pathways by combining a pan-PI3K inhibitor (Buparlisib) and a PARP1 inhibitor (Olaparib) on a panel of TNBC cell lines with distinct mutational profiles and proportions of CSCs. We observed differential sensitivity to this dual inhibition strategy and varying cellular stress and resistance responses across eight TNBC lines. The dual chemotherapeutic effect is associated with a reduction in S-phase cells, an increased in apoptotic cells and elevated expression of cleaved PARP, indicating a provoked replicative stress response. We observed that PARP/PI3K inhibition efficacy was potentiated by repeated administration in some TNBC lines and identified critical treatment schedules, which further potentiated the dual chemotherapeutic effect. Dual inhibition induced small but significant increases in CSC relative abundance as marked by CD44+/CD24−/lowor ALDH1+cells and increased stress and survival signaling in multiple TNBC cell lines, suggesting this sub-population contributes to TNBC chemoresistance. These results suggest the additive effects of PARP and PI3K inhibition against CSC phenotypes may be enhanced by temporally-staged administration in TNBC cells.
ExploringAlu-Driven DNA Transductions in the Primate Genomes
Authors: Halabian Reza , Storer Jessica M. , Hoyt Savannah J. , Hartley Gabrielle A. , Brosius Jürgen , O’Neill Rachel J. , Makałowski Wojciech 
Published: May 2024

AbstractLong terminal repeats (LTRs) and non-LTRs retrotransposons, aka retroelements, collectively occupy a substantial part of the human genome. Certain non-LTR retroelements, such as L1 and SVA, have the potential for DNA transduction, which involves the concurrent mobilization of flanking non-transposon DNA during retrotransposition. These events can be detected by computational approaches. Despite being the most abundant short interspersed sequences (SINEs) that are still active within the genomes of humans and other primates, the transduction rate caused byAlusequences remains unexplored. Therefore, we conducted an analysis to address this research gap and utilized an in-house program to probe for the presence ofAlu-related transductions in the human genome. We analyzed 118,489 full-lengthAluY subfamilies annotated within the first complete human reference genome, T2T-CHM13. For comparative insights, we extended our exploration to two non-human primate genomes, the chimpanzee and the rhesus monkey. After manual curation, our findings did not confirm anyAlu-mediated transductions, whose source genes are, unlike L1 or SVA, transcribed by RNA polymerase III, implying that they are infrequent or possibly absent not only in the human but also in chimpanzee and rhesus monkey genomes. Although we identified loci in which the 3’ Target Site Duplication (TSD) was located distantly from the retrotransposedAluYs, a transduction hallmark, our study could not find further support for such events. The observation of these instances can be explained by the incorporation of other nucleotides into the poly(A) tails in conjunction with polymerase slippage.
Structure of a human monoclonal antibody in complex with Outer surface protein C (OspC) of the Lyme disease spirochete,Borreliella burgdorferi
Authors: Rudolph Michael J. , Chen Yang , Vorauer Clint , Vance David J , Piazza Carol Lyn , Willsey Graham G , McCarthy Kathleen , Muriuki Beatrice , Cavacini Lisa A. , Guttman Miklos , Mantis Nicholas J 
Published: May 2024

AbstractLyme disease is a tick-borne, multisystem infection caused by the spirochete,Borreliella burgdorferi. Although antibodies have been implicated in the resolution of Lyme disease, the specific B cell epitopes targeted during human infections remain largely unknown. In this study, we characterized and defined the structural epitope of a patient-derived bactericidal monoclonal IgG (“B11”) against Outer surface protein C (OspC), a homodimeric lipoprotein necessary forB. burgdorferitick-mediated transmission and early-stage colonization of vertebrate hosts. High-resolution epitope mapping was accomplished through hydrogen deuterium exchange-mass spectrometry (HDX-MS) and X-ray crystallography. Structural analysis of B11 Fab-OspCAcomplexes revealed the B11 Fabs associated in a 1:1 stoichiometry with the lateral faces of OspCAhomodimers such that the antibodies are essentially positioned perpendicular to the spirochete’s outer surface. B11’s primary contacts reside within the membrane proximal regions of α-helices 1 and 6 and adjacent loops 5 and 6 in one OspCAmonomer. In addition, B11 spans the OspCAdimer interface, engaging opposing α-helix 1’, α-helix 2’, and loop 2-3’ in the second OspCAmonomer. The B11-OspCAstructure is reminiscent of the recently solved mouse transmission blocking monoclonal IgG B5 in complex with OspCA, indicating a mode of engagement with OspC that is conserved across species. In conclusion, we provide the first detailed insight into the interaction between a functional human antibody and an immunodominant Lyme disease antigen long considered an important vaccine target.
Genome-wide association for loci influencing thermal performance curves inNeurospora crassa
Authors: Räsänen Emmi , Moghadam Neda N. , Sidhu Karendeep , Summanen Pauliina A. M. , Littunen Henna-Riikka , Ketola Tarmo , Kronholm Ilkka 
Published: May 2024

AbstractTemperature poses a unique challenge to ectothermic species, as it affects all biochemical reactions in the cell and causes physiological stress. The effect of temperature on an organism can be described by a thermal performance curve (TPC), which displays organismal performance, such as growth rate, as a function of temperature. Previous studies on thermal performance have revealed different amounts of genetic variation and trade-offs in TPC shape and position within species and populations. However, very little is known about the genetic architecture of TPCs on the level of individual loci and alleles. We asked what is the identity of loci contributing to genetic variation in TPCs, and do the alleles exhibit trade-offs or thermodynamic scaling across the temperature range? We used genome-wide association mapping to find loci influencing growth rate at different temperatures and TPC traits in the filamentous fungusNeurospora crassa. We also evaluated the directions and magnitudes of allelic effects to investigate possible trade-offs. We observed both unique associations at specific temperatures, as some loci affected growth rate only at low, intermediate, or high temperatures, and associations that were shared across multiple temperatures. However, only weak evidence of trade-offs was detected, indicating that the evolution of TPCs inN. crassais not constrained by allelic effects in opposite directions at hot and cold temperatures. Our findings indicate that trade-offs contribute little to variation in TPCs.
Engineering bacterial protein polymers to support human pluripotent stem cell growth and differentiation in culture
Authors: Creigh Adam R. , Waller Helen , Lakey Jeremy H. , Chrzanowska-Lightowlers Zofia M. , Lightowlers Robert N. , Peters Daniel T. 
Published: May 2024

AbstractInduced pluripotent stem cells (iPSCs) are of significant value due to their wide ranging potential, removing the need for embryonic material. To successfully culture, expand and differentiate these cells, it is crucial to maintain a precise biological environment, including an appropriate attachment substrate. Commonly used attachment substrates include recombinant extracellular matrix (ECM) components like vitronectin, as well as animal-derived ECM mixes such as GelTrex and Matrigel. However, there is growing interest in exploring alternative approaches to support bioactivity of cells. One approach that is gaining traction is the use of the Caf1 protein ofYersinia pestis. This protein is appealing primarily due to its stability, modularity, and ease of production. In this study, we have developed novel variants of Caf1 that effectively support the growth and differentiation of iPSCs, performing at least as well as GelTrex. Our findings highlight the potential of Caf1 laminin and vitronectin mimics as viable alternatives for supporting iPSC growth and differentiation. The successful development of these Caf1 variants opens new avenues for the field, paving the way for better defined, more cost-effective and readily available attachment substrates in iPSC research and applications.