bluuebunny/crossref_metadata_2025_split huggingface dataset:
Valproic Acid–Associated Hyperammonemia
Authors: Wong Yiu-Ching Jennifer , Fan Julia , Wan Andrea , Mihic Tamara , Gnyra Michelle 
Published: April 2023

Abstract

Background
Hyperammonemia is an adverse effect that poses clinical uncertainty around valproic acid (VPA) use. The prevalence of symptomatic and asymptomatic hyperammonemia and its relationship to VPA concentration is not well established. There is also no clear guidance regarding its management. This results in variability in the monitoring and treatment of VPA–induced hyperammonemia. To inform clinical practice, this systematic review aims to summarize evidence available around VPA-associated hyperammonemia and its prevalence, clinical outcomes, and management.

Methods
An electronic search was performed through Ovid MEDLINE, Ovid Embase, Web of Science, and PsycINFO using search terms that identified hyperammonemia in patients receiving VPA. Two reviewers independently performed primary title and abstract screening with a third reviewer resolving conflicting screening results. This process was repeated during the full-text review process.

Results
A total of 240 articles were included. Prevalence of asymptomatic hyperammonemia (5%–73%) was higher than symptomatic hyperammonemia (0.7%–22.2%) and occurred within the therapeutic range of VPA serum concentration. Various risk factors were identified, including concomitant medications, liver injury, and defects in carnitine metabolism. With VPA discontinued, most symptomatic patients returned to baseline mental status with normalized ammonia level. There was insufficient data to support routine monitoring of ammonia level for VPA-associated hyperammonemia.

Conclusions
Valproic acid–associated hyperammonemia is a common adverse effect that may occur within therapeutic range of VPA. Further studies are required to determine the benefit of routine ammonia level monitoring and to guide the management of VPA-associated hyperammonemia.
Recurrent Swelling in Pediatric Cochlear Implant Patients
Authors: Shaida Zara , Magos Tiarnan , Kanona Hala , Shaida Azhar 
Published: April 2023

Objective
To determine the prevalence, characteristics, and outcomes of pediatric patients with recurrent swelling over their cochlear implant receiver package.

Study Design
Retrospective case review.

Setting
Tertiary referral center.

Patients
A total of 332 bilateral cochlear implant patients under the age of 18 years were reviewed. Twelve patients with more than one episode of swelling around their cochlear implant receiver package were isolated. Patients with clinical evidence of infection were excluded from the study. The etiology of hearing loss was heterogeneous.

Intervention
Three patients underwent ultrasound, and three patients underwent bedside aspiration. Most patients were treated with 7 days of oral broad-spectrum antibiotics.

Main Outcome Measure
Incidence, frequency, and course of recurrent swelling around cochlear implant receiver packages.

Results
The first swelling appeared between 0.86 and 9.95 years after surgery (mean, 3.38), and the occurrence of the last episode ranged from 0.06 to 3.42 years from the current date (mean, 1.04). The total number of episodes ranged from 2 to 18 (mean, 6). Seven patients had unilateral swellings, and five had bilateral swellings. Swellings were associated with upper respiratory tract infection or minor trauma, or had no identifiable cause. Aspiration in three cases showed evidence of altered blood.

Conclusions
Recurrent otherwise asymptomatic swelling over cochlear implant receiver packages in children is more common than initially thought. Possible causes include hematoma and seroma secondary to upper respiratory tract infection. The incidence and the timing of swelling are variable. There were no swelling-related device failures or reimplantations so patients and parents can be reassured about the long-term outcome.
Long Noncoding RNA MIR600HG Binds to MicroRNA-125a-5p to Prevent Pancreatic Cancer Progression Via Mitochondrial Tumor Suppressor 1–Dependent Suppression of Extracellular Regulated Protein Kinases Signaling Pathway
Authors: Chen Fang , Zheng Xiang , Liang Wenmei , Jiang Chunxia , Su De , Fu Bao 
Published: April 2023

Objectives
Significance of long noncoding RNAs in pancreatic cancer (PC) progression has been documented. Here, we identified a novel long noncoding RNA MIR600HG in PC and its underlying mechanism during PC progression.

Methods
Through bioinformatics analysis, we selected MIR600HG, microRNA-125a-5p (miR-125a-5p), and mitochondrial tumor suppressor 1 (MTUS1) as objects with their expression patterns assayed in the collected PC tissues and PC cells. Pancreatic cancer cells were manipulated with ectopic expression and deficiency of MIR600HG, miR-125a-5p, and/or MTUS1 for assaying cell biological processes in vitro and tumorigenesis in vivo.

Results
MIR600HG and MTUS1 levels were downregulated and miR-125a-5p was upregulated in PC tissues and cells. MIR600HG could bind to miR-125a-5p, while miR-125a-5p negatively targeted MTUS1. MIR600HG resulted in suppression in malignant properties of PCs. All these changes could be reversed by miR-125a-5p elevation. In addition, miR-125a-5p targeted MTUS1 to activate the extracellular regulated protein kinases signaling pathway. In vivo experiment also verified the inhibitory role of MIR600HG in PC.

Conclusions
Taken together, MIR600HG acts as an inhibitor for PC progression by upregulating miR-125a-5p–mediated MTUS1 through extracellular regulated protein kinases pathway.
Role of Immunohistochemistry in Suspected Pancreatic Ductal Adenocarcinoma
Authors: Valentini Anna M. , Savino Maria T. , Donghia Rossella , Schena Nicolò , Arborea Graziana 
Published: April 2023

Objectives
Differential diagnosis between pancreatic ductal adenocarcinoma (PDAC) and benign mimickers can be very difficult on small histological samples, such as fine needle aspiration biopsies (FNAB). We aimed to investigate the diagnostic value of immunostaining for IMP3, Maspin, S100A4, S100P, TFF2, and TFF3 in FNAB pancreatic lesions.

Methods
We prospectively enrolled 20 consecutive patients with suspected PDAC, collecting FNABs at our department between 2019 and 2021.

Results
Three of the 20 enrolled patients resulted negative for all immunohistochemical markers, while all the others were positive for Maspin. All other immunohistochemistry (IHC) markers had sensitivity and accuracy of less than 100%. On the basis of the IHC, the preoperative diagnosis on FNAB was nonmalignant lesions in the IHC negative cases and PDAC in the others. All patients subsequently underwent surgery for the pancreatic solid mass demonstrated by imaging techniques. The concordance between the preoperative and postoperative diagnosis was 100%; all IHC negative samples were diagnosed on surgical specimens as chronic pancreatitis and Maspin-positive samples as PDAC.

Conclusions
Our results demonstrate that even in the presence of little histological material, such as FNAB, the use of Maspin alone is sufficient to discriminate between PDAC and nonmalignant pancreatic lesions, with 100% accuracy.
The Clinical Characteristics and Outcome of Elderly Patients With Acute Pancreatitis
Authors: Wang Qiu , Chen Yiqiu , Huang Ping , Su De , Gao Fei , Fu Xiaoyun , Fu Bao 
Published: April 2023

Objectives
This study aimed to identify the risk factors for the progression of acute pancreatitis (AP) to severe acute pancreatitis (SAP) and death in elderly patients.

Methods
This was a single-center retrospective study conducted in a tertiary teaching hospital. Data on patient demographics, comorbidities, duration of hospitalization, complications, interventions, and mortality rates were collected.

Results
Between January 2010 and January 2021, 2084 elderly patients with AP were included in this study. The mean age of the patients was 70.0 years (standard deviation, 7.1 years). Among them, 324 (15.5%) had SAP and 105 died (5.0%). The 90-day mortality rate in the SAP group was significantly higher than that in the AP group (P < 0.0001). Multivariate regression analysis revealed that trauma, hypertension, and smoking were risk factors for SAP. After multivariate adjustment, acute respiratory distress syndrome, acute kidney injury, sepsis, organ perforation, and abdominal hemorrhage were associated with higher 90-day mortality.

Conclusions
Traumatic pancreatitis, hypertension, and smoking are independent risk factors for SAP in elderly patients. Acute respiratory distress syndrome, acute kidney injury, sepsis, organ perforation, and abdominal hemorrhage are independent risk factors for death in elderly patients with AP.
Risk Factors for Relapse and/or Prolonged Glucocorticoid Therapy in Polymyalgia Rheumatica
Authors: Vinicki Juan Pablo , Gut Oscar , Maliandi María del Rosario , Velasco Zamora Jose Luis , Linarez Miguel , Cusa Maria Alejandra , Got Julio , Spinetto Maria Andrea , Estevez Adrian Jorge , Brigante Alejandro , Curti Ana Carolina , Costi Ana Carolina , Cavallasca Javier 
Published: April 2023

Background
In polymyalgia rheumatica (PMR) relapses and long-term GC dependency are common. We assessed risk factors for higher relapse rate and/or prolonged glucocorticoid therapy in PMR patients.

Methods
A multicenter and observational study (chart review) of PMR patients seen between 2006 and 2021 who had at least a 3-month follow-up period after starting GCs was performed. Results were expressed as median and interquartile range 25th–75th or mean ± standard deviation for numerical variables and percentage for categorical ones. Relapse versus nonrelapse groups were compared using Cox proportional analysis. Hazards ratios (HRs) with 95% confidence intervals (CIs) are reported. In all cases, a p value <0.05 was considered to indicate statistical significance.

Results
We included 185 patients (69.1% female). The median follow-up time was 17.1 months (interquartile range, 6.8–34.7). Incidence of relapses was 1.2 per 100 persons/month. In univariate analysis, PMR patients with a previous history of dyslipidemia had a lower risk of relapse (HR, 0.55; 95% CI, 0.33–0.94; p = 0.03); high-dose GC (HR, 2.35; 95% CI, 1.42–3.87; p = 0.001) and faster GC dose reduction had higher risk of relapse (HR, 3.04; 95% CI, 1.77–5.21; p = 0.001). In multivariate analysis, a previous history of dyslipidemia had a lower risk of relapse (HR, 0.54; 95% CI, 0.32–0.92; p = 0.023), and high dose of GC (HR, 2.46; 95% CI, 1.49–4.08; p = 0.001) remained the only risk factors for relapse.

Conclusions
Lower doses of corticosteroids and a slow rate of reduction are critical to avoid relapse in PMR. Risk factors for higher relapse rate rely on therapy more than clinical characteristics of the patients at the time of diagnosis of PMR.
Technical Basics and Clinical Benefits of Photon-Counting CT
Authors: Flohr Thomas , Schmidt Bernhard 
Published: April 2023

AbstractNovel photon-counting detector CT (PCD-CT) has the potential to address the limitations of previous CT systems, such as insufficient spatial resolution, limited accuracy in detecting small low-contrast structures, or missing routine availability of spectral information. In this review article, we explain the basic principles and potential clinical benefits of PCD-CT, with a focus on recent literature that has grown rapidly since the commercial introduction of a clinically approved PCD-CT.
Multi-Site Implementation of an American College of Surgeons Geriatric Surgery Quality Improvement Initiative
Authors: Ma Meixi , Peters Xane D , Zhang Lindsey M , Hornor Melissa , Christensen Kataryna , Coleman JoAnn , Finlayson Emily , Flood Kellie L , Katlic Mark , Lagoo-Deenadayalan Sandhya , Robinson Thomas N , Rosenthal Ronnie A , Tang Victoria L , Ko Clifford Y , Russell Marcia M 
Published: April 2023

Background:
The American College of Surgeons (ACS) Coalition for Quality in Geriatric Surgery (CQGS) identified standards of surgical care for the growing, vulnerable population of aging adults in the United States. The aims of this study were to 1) determine implementation feasibility for 30 selected standards, 2) identify barriers and best practices in their implementation, and 3) further refine these geriatric standards and verification process.

Study Design:
The CQGS requested participation from hospitals involved in the ACS National Surgical Quality Improvement Project (NSQIP) Geriatric Surgery Pilot Project, prior CQGS feasibility analyses, and hospitals affiliated with a core development team member. 30 standards were selected for implementation. Following implementation, site visits were conducted, and post-visit surveys were distributed.

Results :
Eight hospitals were chosen to participate. Program management (55%), immediate preoperative and intraoperative clinical care (62.5%), and postoperative clinical care (58%) had the highest mean percentage of “Fully Compliant” standards. Goals and decision making (30%), preoperative optimization (28%), and transitions of care (12.5%) had the lowest mean percentage of “Fully Compliant” standards. Best practices and barriers to implementation were identified across 13 of the 30 standards. Over 80% of the institutions reported that participation changed the surgical care provided for older adults.

Conclusion:
This study represents the first national implementation assessment undertaken by the ACS for one of its quality programs. The CQGS pilot testing was able to demonstrate implementation feasibility for 30 standards, identify challenges and best practices, and further inform dissemination of the ACS Geriatric Surgery Verification Program.
Polysubstance use in South Asia
Authors: Mandal Piyali , Mittal Sumegha , Chadda Rakesh Kumar 
Published: April 2023

Purpose of reviewPolysubstance use is very common in the world, but there has been limited research in this area. South Asia is sandwiched between two of the world's largest heroin producing areas: the Golden Crescent and the Golden Triangle. The burden and prevalence of polysubstance use have not been estimated in this region of the world. We review the research findings on polysubstance use in different South Asian countries. The review also comments on the gaps in knowledge regarding polysubstance use in this region of the world.Recent findingsThe available literature on polysubstance use from South Asia suggests its widespread presence in the region, ranging from 20 to 90%, more commonly among illicit opioid drug users and injection drug users. Most of the available data is from epidemiological studies. There are few studies on the adverse effects of polysubstance use, but the limited data clearly suggests an elevated risk of comorbid psychopathology and health problems.SummaryPolysubstance use still lacks a consensus definition. There is a need of more research on its prevalence, effects on health, and prevention and treatment.
Changes in hospital staff’ mental health during the Covid-19 pandemic: longitudinal results from the international COPE-CORONA study
Authors: Lanzara Roberta , Conti Chiara , Rosa Ilenia , Pawłowski Tomasz , Malecka Monika , Rymaszewska Joanna , Porcelli Piero , Stein Barbara , Waller Christiane , Müller Markus M. ,   the Cope-Corona Study Group
Published: April 2023

AbstractThis longitudinal study aimed to explore anxiety and depressive symptoms, individual resources, and job demands in a multi-country sample of 612 healthcare workers (HCWs) during the COVID-19 pandemic. Two online surveys were distributed to HCWs in seven countries (Germany, Andorra, Ireland, Spain, Italy, Romania, Iran) during the first (May-October 2020, T1) and the second (February-April 2021, T2) phase of the pandemic, assessing sociodemographic characteristics, contact with COVID-19 patients, anxiety and depressive symptoms, self-compassion, sense of coherence, social support, risk perception, and health and safety at the workplace. HCWs reported a significant increase in depressive and anxiety symptoms. HCWs with high depressive or anxiety symptoms at T1 and T2 reported a history of mental illness and lower self-compassion and sense of coherence over time. Risk perception, self-compassion, sense of coherence, and social support were strong independent predictors of depressive and anxiety symptoms at T2, even after controlling for baseline depressive or anxiety symptoms and sociodemographic variables. These findings pointed out that HCWs during the COVID-19 outbreak experienced a high burden of psychological distress. The mental health and resilience of HCWs should be supported during disease outbreaks by instituting workplace interventions for psychological support.
Application of the WHO Nutrient Profile Model to products on the German market: Implications for proposed new food marketing legislation in Germany
Authors: Holliday Nicole , Leibinger Anna , Huizinga Oliver , Klinger Carmen , Okanmelu Elochukwu , Geffert Karin , Rehfuess Eva , von Philipsborn Peter 
Published: April 2023

AbstractBackgroundExposure to marketing for foods high in sugar, salt, and fat is considered a key risk factor for childhood obesity. To support efforts to limit such marketing, the World Health Organization Regional Office for Europe has developed a nutrient profile model (WHO NPM). Germany’s Federal Ministry of Food and Agriculture plans to use this model in proposed new legislation on food marketing directed towards children, but the model has not yet been tested on products on the German market. Against this backdrop, the present paper aims to assess the feasibility and implications of implementing the WHO NPM in Germany.MethodsWe applied the WHO NPM to a random sample of 660 food and beverage products across 22 product categories on the German market drawn from Open Food Facts, a publicly available product database. We calculated the share of products permitted for marketing to children based on the WHO NPM’s nutrient and ingredient criteria, both under current market conditions and for several hypothetical reformulation scenarios. We also assessed effects of adaptations to and practical challenges in applying the WHO NPM.ResultsThe median share of products permitted for marketing to children across the model’s 22 product categories was 20% (interquartile range (IQR) 3-59%) and increased to 38% (IQR 11-73%) with model adaptations for fruit juice and milk proposed by Germany’s Federal Ministry of Food and Agriculture. With targeted reformulation (assuming a 30% reduction in fat, sugar, sodium and/or energy) the share of products permitted for marketing to children increased substantially (defined as a relative increase by at least 50%) in several product categories (including bread, processed meat, yogurt and cream, ready-made and convenience foods, and savoury plant-based foods), but changed less in the remaining categories. Practical challenges in applying the model included the ascertainment of the trans-fatty acid content of products, and the classification of products not required to carry nutrient declarations, such as fresh meats, fish, and similar products.DiscussionThe application of the WHO NPM to a random sample of food and beverage products on the German market was found to be feasible. Its use in the proposed new legislation on food marketing in Germany seems likely to serve its intended public health objective of limiting marketing in a targeted manner specifically for less healthy products. It seems plausible that it may incentivise reformulation in some product categories. Practical challenges in applying the model could be addressed with appropriate adaptations and procedural provisions.
National Estimates for the Percentage of all Readmissions With Demographic Features, Morbidity, Overall and Gender-specific Mortality of Transcutaneous vs Open Surgical Tricuspid Valve Replacement/Repair
Authors: Khan Muhammad Shayan , Baqi Abdul , Ghumman Ghulam Mujtaba , Ullah Waqas , Shah Jay , Sattar Yasar , Mir Tanveer , Sheikh Zain , Tahir Ayesha , Salman Fnu , Baghal Moaaz , Luthra Kritika , Khatri Vinod , Waqar Zainulabedin , Taleb Mohammed , Ali Syed Sohail 
Published: April 2023

AbstractAimsTo determine national estimates for the percentage of all readmissions with demographic features, length of stay, cost analysis, comorbidities, overall and gender-specific mortality and complications of transcutaneous Tricuspid replacement/repair [TTVR] vs. open surgical tricuspid valve replacement/repair [Open TVR].MethodsData was extrapolated from the NRD databases 2015-19. Of the 75,266,750 (unweighted) cases recorded in the 2015 – 2019 dataset, 429 had one or more of the percutaneous approach codes as per the ICD-10 data set, and 10077 had one or more of the open approach codes.ResultsOverall, the number of cases performed each year through open TVR was higher than TTVR, but there was an increased trend towards the TTVR every passing year. TTVR was performed more in females and advanced age groups than open TVR. The length of stay and cost was lower in the TTVR group than in open TVR. Patients undergoing TTVR had more underlying comorbidities like CHF, HTN, and uncomplicated DM. Overall mortality was 3.49 % in TTVR vs. 6.09% in open TVR. Gender-specific analysis demonstrated higher female mortality in the open TVR compared to TTVR (5.45% vs. 3.03 %). Male mortality was statistically insignificant between the two groups (6.8%% vs. 4.3%, p-value 0.15%). Patients with TTVR had lower rates of complications than open TVR, except for arrhythmias, which were higher in TTVR. Patients undergoing open TVR required more intracardiac support, such as IABP and Impella, than TTVR.ConclusionTranscatheter tricuspid valve replacement/repair is an emerging alternative to open surgical repair/replacement in patients with tricuspid valve diseases, especially tricuspid regurgitation. Despite having more underlying comorbidities, the TTVR group had lower in- hospital mortality, hospital cost, length of stay, and fewer complications than open TVR.
Epigenetically-regulated RNA-binding proteins signify malaria hypnozoite dormancy
Authors: Toenhake Christa Geeke , Voorberg-van der Wel Annemarie , Wu Haoyu , Kanyal Abhishek , Nieuwenhuis Ivonne Geessina , van der Werff Nicole Maria , Hofman Sam Otto , Zeeman Anne-Marie , Kocken Clemens Hendricus Martinus , Bártfai Richárd 
Published: April 2023

SUMMARYDormancy enables relapsing malaria parasites, such asPlasmodium vivaxandcynomolgi, to survive unfavorable conditions and maximize chances for transmission. It is caused by hypnozoites, parasites remaining quiescent inside hepatocytes before reactivating and establishing blood-stage infection. We integrated various omics approaches to explore gene-regulatory mechanisms underlying hypnozoite formation and reactivation. Genome-wide profiling of epigenetic marks identified a small set of genes that gets epigenetically silenced during hepatic infection of relapsing parasites. Furthermore, by combining single-cell transcriptomics, chromatin accessibility profiling and fluorescentin situRNA hybridization, we show that these genes are exclusively expressed in hypnozoites and their silencing precedes parasite development. Intriguingly, these hypnozoite-specific genes mainly encode proteins with RNA-binding domains. We, hence, propose that repressive RNA-binding proteins keep hypnozoites in a developmentally competent but dormant state and heterochromatin-mediated silencing of the corresponding genes enables hypnozoite reactivation. Further testing of this hypothesis could provide clues for targeted reactivation and killing of these vicious pathogens.