bluuebunny/crossref_metadata_2025_split huggingface dataset:
Management of velopharyngeal insufficiency by a new modification of sphincter pharyngoplasty technique in cleft palate patients, clinical and radiographical prospective study
Authors: Hamdy Jafar , Yacoub Hikmat 
Published: September 2024

Background:
This study was designed to investigate the effectiveness and outcome of a new modification of the sphincter pharyngoplasty technique in the treatment of velopharyngeal insufficiency patients, with the determination of a specific dimension of velopharyngeal port and velum length of no hypernasality, snoring, and nasal regurgitation potential.

Materials and methods:
The study included 10 patients, who were suffering from consistent hypernasal speech after failure of conservative speech therapy. Clinical and radiographic measurements of the velopharyngeal port and velum length before and after surgery were done, with clinical patient follow-up to assess snoring and nasal regurgitation after surgery for 1, 6, and 12 months.

Results:
Before surgery, the mean clinical anteroposterior distance/velopharyngeal depth was 16.40±1.7 mm, and the mediolateral distance was 20.20±3.4 mm. After surgery, the mean anteroposterior distance decreased to 8±0.9 mm, and the mean mediolateral distance decreased to 12.60±2.06 mm. Both measurements showed statistically significant (P=0.0001). After 12 months postoperatively, the radiographic CT axial anteroposterior distance was 12.09±1.4 mm, and the mean mediolateral distance was 19.82±5.6 mm, compared to the mean CT anterioposterior before surgery 15.60±2 mm and mediolaterally 21.28±2.7 mm. The anteroposterior measurement showed a statistically significant (P=0.002), while the mediolateral measurement did not (P=0.3). The mean velum length before surgery was 25.80±1.5 mm and 27.03±0.6 mm after 12 months postoperatively. Snoring and nasal regurgitation occurrence were assessed at 1, 6, and 12 months postoperatively, with all reports being negative.

Conclusion:
Sphincter pharyngoplasty using posterior tonsillar pillars for treating VPI patients results in improved speech outcomes without snoring or nasal regurgitation.
Transpulmonary Pressure-Guided Mechanical Ventilation in Severe Acute Respiratory Distress Syndrome in PICU: Single-Center Retrospective Study in North India, 2018–2021
Authors: Sachdev Anil , Kumar Anil , Mehra Bharat , Gupta Neeraj , Gupta Dhiren , Gupta Suresh , Chugh Parul 
Published: September 2024

Objectives:
In this study, we have reviewed the association between esophageal pressure-guided positive end-expiratory pressure (PEEP) setting and oxygenation and lung mechanics with a conventional mechanical ventilation (MV) strategy in patient with moderate to severe pediatric acute respiratory distress syndrome (PARDS).

Design:
Retrospective cohort, 2018–2021.

Setting:
Tertiary PICU.

Patients:
Moderate to severe PARDS patients who required MV with PEEP of greater than or equal to 8 cm H2O.

Interventions:
Esophageal pressure (i.e., transpulmonary pressure [PTP]) guided MV vs. not.

Measurements and Main Results:
We identified 26 PARDS cases who were divided into those who had been managed with PTP-guided MV (PTP group) and those managed with conventional ventilation strategy (non-PTP). Oxygenation and lung mechanics were compared between groups at baseline (0 hr) and 24, 48, and 72 hours of MV. There were 13 patients in each group in the first 24 hours. At 48 and 72 hours, there were 11 in PTP group and 12 in non-PTP group. On comparing these groups, first, use of PTP monitoring was associated with higher median (interquartile range) mean airway pressure at 24 hours (18 hr [18–20 hr] vs. 15 hr [13–18 hr]; p = 0.01) and 48 hours (19 hr [17–19 hr] vs. 15 hr [13–17 hr]; p = 0.01). Second, use of PTP was associated with higher PEEP at 24, 48, and 72 hours (all p < 0.05). Third, use of PTP was associated with lower Fio
2 and greater Pao
2 to Fio
2 ratio at 72 hours. Last, there were 18 of 26 survivors, and we failed to identify an association between use of PTP monitoring and survival.

Conclusions:
In this cohort of moderate to severe PARDS cases undergoing MV with PEEP greater than or equal to 8 cm H2O, we have identified some favorable associations of oxygenation status when PTP-guided MV was used vs. not. Larger studies are required.
Integrating Emotional Health Assessments into Pediatric Care: Initial Learnings from an MOC Part 4 Activity
Authors: Lannon Carole M. , Schuler Christine L. , Thomas LaCrecia , Gehring Emily , Mann Keith J. , Leslie Laurel K. 
Published: September 2024

Introduction:
Living with a chronic condition often impacts the emotional health of children. Pediatricians frequently feel unprepared to address these concerns. The American Board of Pediatrics Roadmap Project aims to support these clinicians. We describe the results from the initial cohort of pediatricians who completed the American Board of Pediatrics Maintenance of Certification (MOC) Roadmap Part 4 activity.

Methods:
The Roadmap MOC activity uses a standardized improvement template with accompanying resources to guide participants. Physicians self-assess their ability to provide emotional health support by completing a Roadmap Readiness Checklist and creating a personal project relevant to their practice. They collect data at three time points: baseline, midpoint, and completion for two measures (the Readiness Checklist and a participant-selected measure). Physicians also reflect on their experience.

Results:
Of the initial cohort of 29 physicians, 22 submitted three sequential checklist assessments. Scores increased for “developing a family resource list” (by 90%), “confidence to address emotional health” (79%), “having a family crisis plan” (78%), and “staff awareness” (34%). Twenty-four physicians who measured whether clinical encounters addressed emotional health documented an increase from 21% to 77%. Physician feedback was positive, for example, “This project has had a profound impact on our care of children.”

Conclusions:
This initial cohort of participants improved on the Readiness Checklist and emotional health assessment. Both generalist and subspecialty pediatricians found the activity useful and relevant, suggesting that this MOC Part 4 activity is a feasible resource for supporting physicians in addressing emotional health.
Glucagon-Like Peptide-1 Agonists
Authors: Stanton Eloise W. , Manasyan Artur , Banerjee Rakhi , Hong Kurt , Koesters Emma , Daar David A. 
Published: September 2024

Background
Glucagon-like peptide-1 (GLP-1) agonists, such as exenatide, liraglutide, dulaglutide, semaglutide, and tirzepatide, effectively manage type 2 diabetes by promoting insulin release, suppressing glucagon secretion, and enhancing glucose metabolism. They also aid weight reduction and cardiovascular health, potentially broadening their therapeutic scope. In plastic surgery, they hold promise for perioperative weight management and glycemic control, potentially impacting surgical outcomes.

Methods
A comprehensive review was conducted to assess GLP-1 agonists' utilization in plastic surgery. We analyzed relevant studies, meta-analyses, and trials to evaluate their benefits and limitations across surgical contexts, focusing on weight reduction, glycemic control, cardiovascular risk factors, and potential complications.

Results
Studies demonstrate GLP-1 agonists' versatility, spanning weight management, cardiovascular health, neurological disorders, and metabolic dysfunction-associated liver diseases. Comparative analyses highlight variations in glycemic control, weight loss, and cardiometabolic risk. Meta-analyses reveal significant reductions in hemoglobin A1C levels, especially with high-dose semaglutide (2 mg) and tirzepatide (15 mg). However, increased dosing may lead to gastrointestinal side effects and serious complications like pancreatitis and bowel obstruction. Notably, GLP-1 agonists' efficacy in weight reduction and glycemic control may impact perioperative management in plastic surgery, potentially expanding surgical candidacy for procedures like autologous flap-based breast reconstruction and influencing outcomes related to lymphedema. Concerns persist regarding venous thromboembolism and delayed gastric emptying, necessitating further investigation into bleeding and aspiration risk with anesthesia.

Conclusions
GLP-1 agonists offer advantages in perioperative weight management and glycemic control in plastic surgery patients. They may broaden surgical candidacy and mitigate lymphedema risk but require careful consideration of complications, particularly perioperative aspiration risk. Future research should focus on their specific impacts on surgical outcomes to optimize their integration into perioperative protocols effectively. Despite challenges, GLP-1 agonists promise to enhance surgical outcomes and patient care in plastic surgery.
A Guide for Active Learning in Synergistic Drug Discovery
Authors: Wang Shuhui , Allauzen Alexandre , Nghe Philippe , Opuu Vaitea 
Published: September 2024

AbstractSynergistic drug combination screening is a promising strategy in drug discovery, but it involves navigating a costly and complex search space. While AI, particularly deep learning, has advanced synergy predictions, its effectiveness is limited by the low occurrence of synergistic drug pairs. Active learning, which integrates experimental testing into the learning process, has been proposed to address this challenge. In this work, we explore the key components of active learning to provide recommendations for its implementation. We find that molecular encoding has a limited impact on performance, while the cellular environment features significantly enhance predictions. Additionally, active learning can discover 60% of synergistic drug pairs with only exploring 10% of combinatorial space. The synergy yield ratio is observed to be even higher with smaller batch sizes, where dynamic tuning of the exploration-exploitation strategy can further enhance performance.
Ex-vivomouse precision cut tumour slices for modelling hepatocellular carcinoma; A 3Rs solution for at-scale drug screening
Authors: Collins Amy L , Kirkness Keara , Ramon-Gil Erik , Tzortzopoulou Eleni , Geh Daniel , Cameron Rainie , Luli Saimir , Khurram Eman , Storey Daniel , Paish Hannah , McDonald David , Filby Andrew , Borthwick Lee A , Oakley Fiona , Mann Derek , Leslie Jack 
Published: September 2024

AbstractDisease modelling is vital for improving knowledge of disease mechanisms and for development of new therapeutic molecules and strategies. Modelling the intact living tumour microenvironment (TME) is increasingly considered to be vital not only for gaining a better understanding of the biology of cancer but for examining the efficacy of novel oncology drugs. To date, pre-clinical mouse models of cancer have represented the mainstay methodology for studying the evolving TME and for determining the effects of potential therapeutic molecules on tumour evolution and growth. Regarding drug screening,in vivomouse models are expensive, require the use of large cohorts of mice and involve the administration of drugs with unknown toxicities to animals which often result in adverse effects that can cause animal suffering and the discontinuation of drug investigations. Hepatocellular carcinoma (HCC) is a primary cancer of the liver for which there is an urgent need for improved systemic treatments due to the disease usually being diagnosed at an advanced stage and current treatments having limited efficacy. To provide a practical solution to the screening of drugs for their likely efficacy in HCC we have developed anex-vivomodel in which orthotopic tumours are excised from the liver and subsequently processed to generate precision-cut tumour slices (PCTS) which provide an intact culture model of the HCC-TME. We describe simplified culture conditions that maintain the viability and metabolic activity of live PCTS which maintain the architecture, cellular complexity, drug sensitivity and responsiveness to immunotherapy of the original tumour. Importantly, we show that HCC derived PCTS can be miniaturised to 96-well scale and modified to express soluble luciferase, which in combination enabled non-destructive screening of a library of 26 drugs at two doses using just 5 tumours as the source for PCTS. This screen identified two small molecules, salinomycin and rottlerin, that have potent anti-tumour activities in HCC-PCTS and subsequently validated salinomycin as effectivein vivo. In summary, we report a 3Rs (reduction, refinement and replacement) solution for study of HCC biology and for 96-well-scale screening of potential therapeutic agents in the context of an intact, metabolically active TME.
Engineered Receptors for Soluble Cell-to-Cell Communication
Authors: Piraner Dan I. , Abedi Mohamad H. , Gonzalez Maria J. Duran , Chazin-Gray Adam , Zhu Iowis , Ravindran Pavithran T. , Schlichthaerle Thomas , Huang Buwei , Lee David , Baker David , Roybal Kole T. 
Published: September 2024

AbstractDespite recent advances in mammalian synthetic biology, there remains a lack of modular synthetic receptors that can robustly respond to soluble ligands and in turn activate cellular functions. Such receptors would have extensive clinical potential to regulate the activity of engineered therapeutic cells, but to date only receptors against cell surface targets have approached clinical translation. To address this gap, we developed a receptor architecture based on synNotch, called SyNthetic Intramembrane Proteolysis Receptor (SNIPR), that has the added ability to be activated by soluble ligands, both natural and synthetic, with remarkably low baseline activity and high fold activation. SNIPRs are able to access an endocytic, pH-dependent cleavage mechanism to achieve soluble ligand sensing, in addition to employing a canonical-like pathway for detecting surface-bound ligands. We demonstrate the therapeutic capabilities of the receptor platform by localizing the activity of CAR T-cells to solid tumors where soluble disease-associated factors are expressed, bypassing the major hurdle of on-target off-tumor toxicity in bystander organs. We further applied the SNIPR platform to engineer fully synthetic signaling networks between cells orthogonal to natural signaling pathways, expanding the scope of synthetic biology. Our design framework enables cellular communication and environmental interactions, extending the capabilities of synthetic cellular networking in clinical and research contexts.
Screening and identification of gene expression in large cohorts of clinical lung cancer samples unveils the major involvement of EZH2 and SOX2
Authors: Niharika  , Roy Ankan , Sadhukhan Ratan , Patra Samir Kumar 
Published: September 2024

AbstractLung adenocarcinoma (LUAD), the primary subtype of Non-Small Cell Lung Cancer (NSCLC), accounts for 80% to 85% of cases. Due to suboptimal screening method, LUAD is often detected in late stage, leading to aggressive progression and poor outcomes. Therefore, early disease prognosis for the LUAD is high priority. In order to identify early detection biomarkers, we conducted a meta-analysis of mRNA expression TCGA and GTEx datasets from LUAD patients. A total of 795 differentially expressed genes (DEGs) were identified by exploring the Network-Analyst tool and utilizing combined effect size methods. DEGs refer to genes whose expression levels are significantly different (either higher or lower) compared to their normal baseline expression levels. KEGG pathway enrichment analysis highlighted the TNF signaling pathway as being prominently associated with these DEGs. Subsequently, using the MCODE and CytoHubba plugins in Cytoscape software, we filtered out the top 10 genes. Among these, SOX2 was the only gene exhibiting higher expression, while the others were downregulated. Consequently, our subsequent research focused on SOX2. Further transcription factor-gene network analysis revealed that enhancer of zeste homolog 2 (EZH2) is a significant partner of SOX2, potentially playing a crucial role in euchromatin-heterochromatin dynamics. Structure of SOX2 protein suggest that it is a non-druggable transcription factor, literature survey suggests the same; hence, we drove our focus to investigate on potential drug(s) targeting EZH2. Molecular docking analyses predicted most probable inhibitors of EZH2. We employed several predictive analysis tools and identified GSK343, as a promising inhibitor of EZH2.
A microinjection protocol for the greater waxworm moth,Galleria mellonella
Authors: Pearce James , Housden Amy , Senior Nicola , Champion Olivia , Prior Joann , Titball Richard , Wakefield James 
Published: September 2024

AbstractA limitation to the non-vertebrate 3Rs modelGalleria mellonellahas been the lack of genetic toolkit. A common requirement for genetic tractability is a method to introduce exogenous material to the unicellular embryo, the most common of which is microinjection. This short article describes a detailed method for rearingGalleria mellonellato collect large amounts of staged embryos and to dechorionate and microinject embryos with limited mortality.Research HighlightsScientific BenefitsMicroinjection allows the introduction of a wide variety of substances, such as DNA, RNA or drugs intoGalleriaembryos, providing the technology needed for genetic engineering, gene editing and functional studies in this important model organism.3Rs BenefitsGalleriais being increasingly used as a partial animal replacement model, especially in the field of infection biology. However, uptake has been limited by the lack of genetic and molecular tools. This protocol takes a step towards removing these barriers by providing a means to introduce substances that can create transgenic or genetically engineeredGalleria.Practical BenefitsProtocol for injecting substances intoGalleria,using for the most part easily accessible equipment.Current ApplicationsGenerating stable transgenic and gene-editedGallerialines.Potential ApplicationsAny technique requiring the introduction of substances toGalleriaembryos. This includes applying existing techniques such as pBac-mediated transgenesis or CRISPR/Cas-based gene-editing to this organism,in order to generate engineered strains ofGalleria. It could also include injection of synthetic mRNAs encoding proteins fused to fluorescent genes (such as GFP) in order to visualise their dynamics in living embryos; and the injection of drugs that perturb particular cell or developmental processes in order to learn more about earlyGalleriadevelopment.
Predictive filtering of sensory response via orbitofrontal top-down input
Authors: Tsukano Hiroaki , Garcia Michellee M. , Dandu Pranathi R. , Kato Hiroyuki K. 
Published: September 2024

AbstractHabituation is a crucial sensory filtering mechanism whose dysregulation can lead to a continuously intense world in disorders with sensory overload. While habituation is considered to require top-down predictive signaling to suppress irrelevant inputs, the exact brain loci storing the internal predictive model and the circuit mechanisms of sensory filtering remain unclear. We found that daily neural habituation in the primary auditory cortex (A1) was reversed by inactivation of the orbitofrontal cortex (OFC). Top-down projections from the ventrolateral OFC, but not other frontal areas, carried predictive signals that grew with daily sound experience and suppressed A1 via somatostatin-expressing inhibitory neurons. Thus, prediction signals from the OFC cancel out behaviorally irrelevant anticipated stimuli by generating their “negative images” in sensory cortices.
The lysosomal membrane protein LAMP2B mediates microlipophagy to target obesity-related disorders
Authors: Sakai Ryohei , Aizawa Shu , Lee-Okada Hyeon-Cheol , Hase Katsunori , Fujita Hiromi , Kikuchi Hisae , Inoue Yukiko U. , Inoue Takayoshi , Kabuta Chihana , Yokomizo Takehiko , Hashimoto Tadafumi , Wada Keiji , Mano Tatsuo , Koyama-Honda Ikuko , Kabuta Tomohiro 
Published: September 2024

SummaryLifestyle diseases, such as obesity, diabetes, and metabolic syndrome, are leading health problems, most of which are related to abnormal lipid metabolism. Lysosomes can degrade lipid droplets (LDs) via microautophagy. Here, we report the molecular mechanism and pathophysiological roles of microlipophagy, regulated by the lysosomal membrane protein LAMP2B. Our study revealed that LAMP2B interacts with phosphatidic acid, facilitating lysosomal-LD interactions and enhancing lipid hydrolysis via microlipophagy depending on endosomal sorting complexes required for transport. Correlative light and electron microscopy demonstrated direct LDs uptake into lysosomes at contact sites. Moreover, LAMP2B overexpression in mice prevents high-fat diet-induced obesity, insulin resistance, and adipose tissue inflammation; liver lipidomics analysis suggested enhanced triacylglycerol hydrolysis. Overall, the findings of this study elucidated the mechanism of microlipophagy, which could be promising for the treatment of obesity and related disorders.
Measurements of extended magnetic fields in laser-solid interaction
Authors: Griff-McMahon J. , Malko S. , Valenzuela-Villaseca V. , Walsh C. A. , Fiksel G. , Rosenberg M. J. , Schaeffer D. B. , Fox W. 
Published: September 2024

Magnetic fields generated from a laser-foil interaction are measured with high fidelity using a proton radiography scheme with x-ray fiducials. In contrast to prior findings under similar experimental conditions, this technique reveals the self-generated, Biermann-battery fields extend beyond the edge of the expanding plasma plume to a radius of over 3.5 mm by t=+1.4 ns. An analysis of two monoenergetic proton populations confirms that proton deflection is dominated by magnetic fields far from the interaction (>2 mm) and electric fields are insignificant. The results are not captured in state-of-the-art magnetohydrodynamics simulations and suggest the need to consider additional physics mechanisms for the magnetic field generation and transport in laser-solid interactions.

Published by the American Physical Society
2024
Additional reviews, perceived credibility and consumer online purchasing behavior: a study of university students in China
Authors: Wang Xulong , Bai Xuejiao , Zhao Liming 
Published: September 2024

PurposeThis study explores the link between additional reviews, credibility, and consumers’ online purchasing behavior.Design/methodology/approachWe employ a 2 × 2 between-subjects design to measure subjects’ purchasing behavior with versus without additional reviews and with important versus non-important attributes. A total of 529 valid questionnaires are collected from university students across 30 Chinese provinces.FindingsThe addition of negative reviews to a positive initial review enhances consumers’ perceived credibility of the reviewer and the overall review content. This effect is positively moderated by the attribute importance in additional reviews. Moreover, we find that as the time interval increases, consumers’ perceived credibility gradually increases but eventually decreases after reaching a certain threshold. In addition, the attribute importance in additional reviews negatively moderates the impact of perceived credibility on consumer purchasing behavior.Originality/valueExisting studies on first and subsequent reviews mainly focus on the difference in perceived usefulness between the two. They do not examine how additional reviews affect potential customers’ perceived credibility and their purchase decision-making. This study bridges the gap between the word-of-mouth literature and marketing practices.