bluuebunny/crossref_metadata_2025_split huggingface dataset:
Site and Mechanism of ML252 Inhibition of Kv7 Voltage-Gated Potassium Channels
Authors: Kanyo Richard , Lamothe Shawn M , Urrutia Arturo , Goodchild Samuel J , Allison W Ted , Dean Richard , Kurata Harley T 
Published: May 2023

AbstractKv7 (KCNQ) voltage-gated potassium channels are critical regulators of neuronal excitability and are candidate targets for development of antiseizure medications. Drug discovery efforts have identified small molecules that modulate channel function and reveal mechanistic insights into Kv7 channel physiological roles. While Kv7 channel activators have therapeutic benefits, inhibitors are useful for understanding channel function and mechanistic validation of candidate drugs. In this study, we reveal the mechanism of a Kv7.2/Kv7.3 inhibitor, ML252. We used docking and electrophysiology to identify critical residues involved in ML252 sensitivity. Most notably, Kv7.2[W236F] or Kv7.3[W265F] mutations strongly attenuate ML252 sensitivity. This tryptophan residue in the pore is also required for sensitivity to certain activators, including retigabine and ML213. We used automated planar patch clamp electrophysiology to assess competitive interactions between ML252 and different Kv7 activator subtypes. A pore-targeted activator (ML213) weakens the inhibitory effects of ML252, whereas a distinct activator subtype (ICA-069673) that targets the voltage sensor does not prevent ML252 inhibition. Using transgenic zebrafish larvae expressing an optical reporter (CaMPARI) to measure neural activity in-vivo, we demonstrate that Kv7 inhibition by ML252 increases neuronal excitability. Consistent with in-vitro data, ML213 suppresses ML252 induced neuronal activity, while the voltage-sensor targeted activator ICA-069673 does not prevent ML252 actions. In summary, this study establishes a binding site and mechanism of action of ML252, classifying this poorly understood drug as a pore-targeted Kv7 channel inhibitor that binds to the same tryptophan residue as commonly used pore-targeted Kv7 activators.ML213 and ML252 likely have overlapping sites of interaction in the pore Kv7.2 and Kv7.3 channels, resulting in competitive interactions. In contrast, the VSD-targeted activator ICA-069673 does not prevent channel inhibition by ML252.
Natural history, clinical characteristics, outcomes, and long-term follow-up of pain-free chronic pancreatitis
Authors: Ahmed Awais , Shah Ishani , Bocchino Rachel , Freedman Steven D , Kothari Darshan J , Sheth Sunil G 
Published: May 2023

Abstract

Background
Chronic pancreatitis (CP) is characterized by chronic abdominal pain and functional insufficiency. However, a small subset of patients with prior acute pancreatitis (AP) and/or underlying risk factors for developing CP may be pain-free at diagnosis and may have a different clinical course. We aimed to compare the clinical characteristics, outcomes, and healthcare utilization between CP patients with and without pain.

Methods
Reviewed patients with established CP were followed in our Pancreas Center between January 2016 and April 2021. Patients without risk factors for developing CP and/or without AP prior to their diagnosis and only with incidental radiologic features of CP were excluded, so as to minimize confounding factors of pancreatopathy unrelated to CP. Patients were divided into painful and pain-free groups to analyze differences in demographics, outcomes, and healthcare utilization.

Results
Of 368 CP patients, 49 (13.3%) were pain-free at diagnosis and had remained so for &gt;9 years. There were no significant differences in body mass index, race, sex, or co-morbidities between the two groups. Pain-free patients were older at diagnosis (53.9 vs 45.7, P = 0.004) and had less recurrent AP (RAP) (43.8% vs 72.5%, P &lt; 0.001) and less exocrine pancreatic insufficiency (EPI) (34.7% vs 65.7%, P &lt; 0.001). Pain-free patients had less disability (2.2% vs 22.0%, P = 0.003), mental illness (20.4% vs 61.0%, P &lt; 0.001), surgery (0.0% vs 15.0%, P = 0.059), and therapeutic interventions (0.0% vs 16.4%, P = 0.005) for pain.

Conclusions
We described a unique subset of patients with underlying risk factors for CP and/or prior AP who were pain-free at diagnosis. They were older at diagnosis, had less EPI and RAP, and overall favorable outcomes with minimal resource utilization.
The Delivery of Person-Centered Care for People Living With Dementia in Residential Aged Care: A Systematic Review and Meta-Analysis
Authors: Berkovic Danielle , Macrae Ann , Gulline Hannah , Horsman Phillipa , Soh Sze-Ee , Skouteris Helen , Ayton Darshini 
Published: May 2023

Abstract

Background and Objectives
Person-centered care is the gold standard of care for people living with dementia, yet few systematic reviews have detailed how it is delivered in practice. This mixed-methods review aimed to examine the delivery of person-centered care, and its effectiveness, for people living with dementia in residential aged care.

Research Design and Methods
A systematic review and meta-analysis. Eligible studies were identified across 4 databases. Quantitative and qualitative studies containing data on person-centered care delivered to people with dementia living in residential aged care were included. Meta-analysis using a random-effects model was conducted where more than 3 studies measured the same outcome. A narrative meta-synthesis approach was undertaken to categorize verbatim participant quotes into representative themes. Risk of bias was undertaken using quality appraisal tools from the Joanna Briggs Institute.

Results
41 studies were identified for inclusion. There were 34 person-centered care initiatives delivered, targeting 14 person-centered care outcomes. 3 outcomes could be pooled. Meta-analyses demonstrated no reduction in agitation (standardized mean difference −0.27, 95% confidence interval [CI], −0.58, 0.03), improvement in quality of life (standardized mean difference −0.63, 95% CI: −1.95, 0.70), or reduced neuropsychiatric symptoms (mean difference −1.06, 95% CI: −2.16, 0.05). Narrative meta-synthesis revealed barriers (e.g., time constraints) and enablers (e.g., staff collaboration) to providing person-centered care from a staff perspective.

Discussion and Implications
The effectiveness of person-centered care initiatives delivered to people with dementia in residential aged care is conflicting. Further high-quality research over an extended time is required to identify how person-centered care can be best implemented to improve resident outcomes.
Inhibition of nonsense-mediated mRNA decay may improve stop codon read-through therapy for Duchenne muscular dystrophy
Authors: Amar-Schwartz Adi , Cohen Yuval , Elhaj Antony , Ben-Hur Vered , Siegfried Zahava , Karni Rotem , Dor Talya 
Published: May 2023

Abstract
Duchene muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are genetic neuromuscular disorders that affect skeletal and cardiac muscle resulting from mutations in the dystrophin gene (DMD), coding for dystrophin protein. Read-through therapies hold great promise for the treatment of genetic diseases harboring nonsense mutations, such as DMD/BMD, as they enable a complete translation of the affected mRNA. However, to date, most read-through drugs have not achieved a cure for patients. One possible explanation for the limitation of these therapies for DMD/BMD is that they rely on the presence of mutant dystrophin mRNAs. However, the mutant mRNAs containing premature termination codons are identified by the cellular surveillance mechanism, the nonsense-mediated mRNA decay (NMD) process, and are degraded. Here, we show that the combination of read-through drugs together with known NMD inhibitors have a synergistic effect on the levels of nonsense-containing mRNAs, among them the mutant dystrophin mRNA. This synergistic effect may enhance read-through therapies’ efficacy and improve the current treatment for patients.
Design and modelling of a small-scale reversible high-temperature heat pump—organic Rankine cycle system for industrial waste heat recovery
Authors: Velanparambil Ravindran Rahul , Huang Ming Jun , Hewitt Neil 
Published: May 2023

Abstract
Organic Rankine cycle (ORC) and heat pump (HP) are two well-established technologies for industrial waste heat recovery. Given the similarity between ORC and HP configurations, a system that can switch between HP and ORC modes with minimal modification is feasible. The reversible system according to the requirement of the industry can exploit waste heat in lower temperature bands operating as a high-temperature heat pump (HTHP) to provide useful process heat or as an ORC system generating power and thus increasing the efficiency of waste heat exploitation. This study discusses the design aspects of a small-scale reversible HTHP—ORC system, including the system layout, component selection, selection of an appropriate working fluid, the operating conditions for both modes and equipment sizing. R1233zd(E) was selected as the refrigerant for the reversible system and an automotive open-drive scroll compressor was found to be suitable, which can also be used as an expander for ORC with minimum modifications. The study also presents the modelling of the reversible system in ORC and HTHP modes including performance analysis of the scroll machine in expander and compressor roles attaining isentropic efficiency values up to 62.4 and 75.4%, respectively. The modelling results show a cycle efficiency of 5.9% (Tev = 102°C, $ \dot{m} $r = 0.064 kg/s) in ORC mode and a coefficient of performance of 4.19 in HTHP mode (for a temperature lift of 49 K with Tsource: 85°C, Ncomp: 2000 rpm).
Poisson Trace Orders
Authors: Brown Ken , Yakimov Milen 
Published: May 2023

AbstractThe two main approaches to the study of irreducible representations of orders (via traces and Poisson orders) have so far been applied in a completely independent fashion. We define and study a natural compatibility relation between the two approaches leading to the notion of Poisson trace orders. It is proved that all regular and reduced traces are always compatible with any Poisson order structure. The modified discriminant ideals of all Poisson trace orders are proved to be Poisson ideals and the zero loci of discriminant ideals are shown to be unions of symplectic cores, under natural assumptions (maximal orders and Cayley–Hamilton algebras). A base change theorem for Poisson trace orders is proved. A broad range of Poisson trace orders are constructed based on the proved theorems: quantized universal enveloping algebras, quantum Schubert cell algebras and quantum function algebras at roots of unity, symplectic reflection algebras, 3D and 4D Sklyanin algebras, Drinfeld doubles of pre-Nichols algebras of diagonal type, and root of unity quantum cluster algebras.
Art by Proxy
Authors: Yanal Robert 
Published: May 2023

Abstract
Cultural theories of art were developed to account for the arthood of nonaesthetic and nonimitative artworks. Historical theories such as those proposed by Jerrold Levinson, James Carney, and Noël Carroll fail to account for the arthood of first art and ethnological objects, as does the disjunctive theory of Stephen Davies. An institutional (artworld-based) theory, such as George Dickie’s 1977 version, can account for the arthood of art made within the context of an artworld. But what of objects that are art now but were not made in an artworld context? I add a supplement to Dickie’s institutional theory: the concept of art by proxy.
Time for a Change: Considering Vancomycin Alternatives for Pediatric Methicillin-Resistant Staphylococcus aureus Bacteremia
Authors: Haynes Andrew S , Maples Holly , Parker Sarah 
Published: May 2023

Abstract
Vancomycin remains the standard of care for treating methicillin-resistant Staphylococcus aureus (MRSA) bacteremia in pediatrics largely because no alternative antibiotic is definitively superior. Long-standing historical precedent and S. aureus’ notable lack of vancomycin resistance are clear benefits, but vancomycin’s use remains plagued by nephrotoxicity and the need for therapeutic drug monitoring, with inadequate consensus on how best to dose or monitor vancomycin in pediatrics. Daptomycin, ceftaroline, and linezolid are all promising alternatives, with improved safety relative to vancomycin. However, inadequate and variable efficacy data limit confidence in their use. Despite this, we contend that it is time for clinicians to reconsider vancomycin’s place in clinical use. In this review, we summarize the supporting data for using vancomycin versus these other anti-MRSA antibiotics, present a framework for antibiotic decision-making that considers patient-specific factors, and discuss approaches to antibiotic selection for various etiologies of MRSA bacteremia. This review aims to help pediatric clinicians choose among the various treatment options for MRSA bacteremia, acknowledging that the optimal antibiotic choice is sometimes uncertain.
Stability of the Interface Between LIPON and LCO During TEM Sample Preparation by FIB
Authors: Rezikyan Aram , Tanner Cameron , Berland Brian 
Published: May 2023

Abstract
An amorphous interphase between lithium phosphorus oxynitride (LIPON) solid electrolyte and lithium cobalt oxide (LCO) has been reported recently in several electron microscopy studies of Li ion thin-film micro-batteries (TFMB), along with its implications to battery operation. However, the origin of the observed interphase at the as-made LIPON/LCO interface remained obscure. In this work, this interface has been characterized comprehensively by scanning electron microscope (SEM) imaging at all steps of the in situ focused ion beam (FIB) lift-out procedure for transmission electron microscopy (TEM) sample preparation. It was found that the interphase is formed during TEM lamella preparation when the portion of LIPON layer contained within the lamella is physically disconnected from the rest of the LIPON layer by FIB. Therefore, it was demonstrated that a disordered interphase can form in LCO at its interface with LIPON during TEM sample preparation by the FIB lift-out procedure and that subtle nature of the interphase formation makes it likely to go unnoticed during the preparation. This interphase was not produced even after galvanostatic charging of a battery with a Li metal anode but inevitably appeared after the FIB lift-out of that sample.
Plant phase extraction: A method for enhanced discovery of the RNA-binding proteome and its dynamics in plants
Authors: Zhang Yong , Xu Ye , Skaggs Todd H , Ferreira Jorge F S , Chen Xuemei , Sandhu Devinder 
Published: May 2023

Abstract
RNA-binding proteins (RBPs) play critical roles in posttranscriptional gene regulation. Current methods of systematically profiling RBPs in plants have been predominantly limited to proteins interacting with polyadenylated (poly(A)) RNAs. We developed a method called plant phase extraction (PPE), which yielded a highly comprehensive RNA-binding proteome (RBPome), uncovering 2,517 RBPs from Arabidopsis (Arabidopsis thaliana) leaf and root samples with a highly diverse array of RNA-binding domains. We identified traditional RBPs that participate in various aspects of RNA metabolism and a plethora of nonclassical proteins moonlighting as RBPs. We uncovered constitutive and tissue-specific RBPs essential for normal development and, more importantly, revealed RBPs crucial for salinity stress responses from a RBP–RNA dynamics perspective. Remarkably, 40% of the RBPs are non-poly(A) RBPs that were not previously annotated as RBPs, signifying the advantage of PPE in unbiasedly retrieving RBPs. We propose that intrinsically disordered regions contribute to their nonclassical binding and provide evidence that enzymatic domains from metabolic enzymes have additional roles in RNA binding. Taken together, our findings demonstrate that PPE is an impactful approach for identifying RBPs from complex plant tissues and pave the way for investigating RBP functions under different physiological and stress conditions at the posttranscriptional level.
Adolescent sleep defects and dopaminergic hyperactivity in mice with a schizophrenia-linked Shank3 mutation
Authors: Bian Wen-Jie , González Oscar C , de Lecea Luis 
Published: May 2023

AbstractShank3 is a shared risk gene for autism spectrum disorders and schizophrenia. Sleep defects have been characterized for autism models with Shank3 mutations; however, evidence has been lacking for the potential sleep defects caused by Shank3 mutation associated with schizophrenia and how early in development these defects may occur. Here we characterized the sleep architecture of adolescent mice carrying a schizophrenia-linked, R1117X mutation in Shank3. We further employed GRABDA dopamine sensor and fiber photometry to record dopamine release in the nucleus accumbens during sleep/wake states. Our results show that homozygous mutant R1117X mice have significantly reduced sleep in the dark phase during adolescence, altered electroencephalogram power, especially during the rapid-eye-movement sleep, and dopamine hyperactivity during sleep but not during wakefulness. Further analyses suggest that these adolescent defects in sleep architecture and dopaminergic neuromodulation tightly correlate with the social novelty preference later in adulthood and predict adult social performance during same-sex social interactions. Our results provide novel insights into the sleep phenotypes in mouse models of schizophrenia and the potential use of developmental sleep as a predictive metric for adult social symptoms. Together with recent studies in other Shank3 models, our work underscores the idea that Shank3-involved circuit disruptions may be one of the shared pathologies in certain types of schizophrenia and autism. Future research is needed to establish the causal relationship among adolescent sleep defects, dopaminergic dysregulation, and adult behavioral changes in Shank3 mutation animals and other models.
Appendectomy in endometriosis: an update on surgical indications and management of uncommon diseases
Authors: Galaviz Veronica D. , Nguyen Anthony D. , Sticco Peter L. , Downing Keith T. 
Published: May 2023

Purpose of review
Abnormal appendiceal disease is commonly encountered following an appendectomy when performed in patients with endometriosis. Appendiceal endometriosis is the most notable finding and can affect up to 39% of patients with endometriosis. Despite this knowledge, guidelines for performing an appendectomy have not been formally established. In this article, we review the surgical indications for an appendectomy at the time of endometriosis surgery and discuss the management of other diseases that may be encountered following the histopathologic evaluation of an excised appendix.

Recent findings
Removal of the appendix in patients with endometriosis contributes to optimal surgical management. Relying on abnormal appendiceal appearance for removal may leave endometriosis-affected appendices. For this reason, utilizing risk factors to guide surgical management is essential. Common appendiceal diseases are sufficiently managed with appendectomy. Uncommon diseases may require further surveillance.

Summary
Emerging data in our field support the performance of an appendectomy at the time of endometriosis surgery. Guidelines for performing a concurrent appendectomy should be formalized to encourage preoperative counselling and management for patients with risk factors for appendiceal endometriosis. Abnormal diseases is frequently encountered after appendectomy in the setting of endometriosis surgery and further management is based on the histopathology of the specimen.
Role of Serial Phlebotomy in the Management of Blunt Solid Organ Injury in Adults
Authors: Frotan Mohammad A. , Edmundson Philip , Cooper Christopher , Tibbs Brian , Garlow Laura , Vandertulip Kaeli , Miller Amy , Aryal Subhash , Roden-Foreman Jacob W. , Shires G. Tom 
Published: May 2023

Background:
The management of blunt spleen and liver trauma has become increasingly nonoperative. There is no consensus on timing or duration of serial hemoglobin and hematocrit monitoring in this patient population.

Objective:
This study examined the clinical utility of serial hemoglobin and hematocrit monitoring. We hypothesized that most interventions occur early in the hospital course, based on hemodynamic instability or physical examination findings rather than serial monitoring.

Methods:
We conducted a retrospective cohort study of adult trauma patients with blunt spleen or liver injury from November 2014 through June 2019 at our Level II trauma center. Interventions were classified as no intervention, surgical intervention, angioembolization, or packed red blood cell transfusion. Demographics, length of stay, total blood draws, laboratory values, and clinical triggers preceding intervention were reviewed.

Results:
A total of 143 patients were studied, of whom 73 (51%) received no intervention, 47 (33%) received an intervention within 4 hr of presentation, and 23 (16%) had interventions beyond 4 hr. Of these 23 patients, 13 received an intervention based on phlebotomy results alone. Most of these patients (n = 12, 92%) received blood transfusion without further intervention. Only one patient underwent operative intervention based on serial hemoglobin results on hospital day 2.

Conclusion:
The majority of patients with these injury patterns either require no intervention or declare themselves promptly after arrival. Serial phlebotomy after initial triage and intervention may add little value in the management of blunt solid organ injury.
Impact of vitamin D receptor polymorphisms in selected metabolic disorders
Authors: Fronczek Martyna , Osadnik Tadeusz , Banach Maciej 
Published: May 2023

Purpose of review
Vitamin D (vitD) can regulate metabolic pathways in adipose tissue and pancreatic β cells by interacting with its vitamin D receptor (VDR). The aim of this study was to review original publications published in the last months and verify the relationship between genetic variants in the VDR gene and type 2 diabetes (T2D), metabolic syndrome (MetS), overweight, and obesity.

Recent findings
The recent studies concern genetic variants located in the coding and noncoding regions of the VDR gene. Some of the described genetic variants may affect VDR expression or posttranslational processing altered functionality or vitD binding capacity of VDR. Nevertheless, the data collected in recent months on the assessment of the relationship between VDR genetic variants and the risk of T2D, MetS, overweight, and obesity still do not give a clear answer to whether they have a direct impact on these metabolic disorders.

Summary
Analysis of the potential association between VDR genetic variants and parameters such as glycemia, body mass index, body fat, and lipid levels improves the current understanding of the pathogenesis of T2D, MetS, overweight, and obesity. A thorough understanding of this relationship may provide important information for individuals with pathogenic variants and enable the implementation of appropriate prevention against the development of these disorders.