bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sensory Outcomes after Neurotization in Nipple-sparing Mastectomy and Implant-based Breast Reconstruction
Authors: Peled Anne Warren , von Eyben Rie , Peled Ziv M. 
Published: December 2023

Background:
Mastectomy and breast reconstruction techniques continue to evolve to optimize aesthetic and reconstructive outcomes. However, the loss of sensation after mastectomy remains a major limitation. This article describes our evolution of a novel approach that we first described in 2019, combining recent advances in breast oncologic, reconstructive, and peripheral nerve surgery to optimize sensory outcomes.

Methods:
Nipple-sparing mastectomy was performed in all patients and involved preservation of lateral intercostal nerves when anatomy was favorable. When nerves could not be preserved without compromising oncologic safety, nipple–areolar complex neurotization was performed using allograft or intercostal autograft from a transected T3, T4, or T5, lateral intercostal nerve to identified subareolar nerve targets. Immediate, prepectoral, direct-to-implant reconstruction was then performed. Acroval one-point moving and one-point static pressure thresholds established baseline sensibility values, which were then repeated at multiple time points postoperatively.

Results:
Outcomes from 47 women (79 breasts) were assessed prospectively. Mean follow-up was 9.2 months (range 6–14 months). At 6 months postoperatively, over 80% of patients had good-to-excellent one-point moving as well as one-point static sensibility scores averaged across all areas tested. None of the patients developed persistent dysesthesia or clinical evidence of neuroma.

Conclusions:
This study represents the largest series reported to date of sensibility outcomes after nipple-sparing mastectomy and implant reconstruction with concurrent neurotization. Sensibility results show that this approach allows for preservation of high degrees of breast and nipple–areolar complex sensation in most patients.
Overexpression of HMGB1 in hepatocytes accelerates PTEN inactivation-induced liver cancer
Authors: Athavale Dipti , Barahona Inés , Song Zhuolun , Desert Romain , Chen Wei , Han Hui , Das Sukanta , Ge Xiaodong , Komakula Sai Santosh B. , Gao Shenglan , Lantvit Daniel , Guzman Grace , Nieto Natalia 
Published: December 2023

Background:
Liver cancer is increasing due to the rise in metabolic dysfunction-associated steatohepatitis (MASH). High-mobility group box-1 (HMGB1) is involved in the pathogenesis of chronic liver disease, but its role in MASH-associated liver cancer is unknown. We hypothesized that an increase in hepatocyte-derived HMGB1 in a mouse model of inactivation of PTEN that causes MASH could promote MASH-induced tumorigenesis.

Methods:
We analyzed publicly available transcriptomics datasets, and to explore the effect of overexpressing HMGB1 in cancer progression, we injected 1.5-month-old Pten
∆Hep mice with adeno-associated virus serotype-8 (AAV8) vectors to overexpress HMGB1-EGFP or EGFP, and sacrificed them at 3, 9 and 11 months of age.

Results:
We found that HMGB1 mRNA increases in human MASH and MASH-induced hepatocellular carcinoma (MASH-HCC) compared to healthy livers. Male and female Pten
∆Hep mice overexpressing HMGB1 showed accelerated liver tumor development at 9 and 11 months, respectively, with increased tumor size and volume, compared to control Pten
∆Hep mice. Moreover, Pten
∆Hep mice overexpressing HMGB1, had increased incidence of mixed HCC-intrahepatic cholangiocarcinoma (iCCA). All iCCAs were positive for nuclear YAP and SOX9. Male Pten
∆Hep mice overexpressing HMGB1 showed increased cell proliferation and F4/80+ cells at 3 and 9 months.

Conclusion:
Overexpression of HMGB1 in hepatocytes accelerates liver tumorigenesis in Pten

∆Hep mice, enhancing cell proliferation and F4/80+ cells to drive MASH-induced liver cancer.
Nutrition assessment and MASH severity in children using the Healthy Eating Index
Authors: Jain Ajay Kumar , Buchannan Paula , Yates Katherine P. , Belt Patricia , Schwimmer Jeffrey B. , Rosenthal Philip , Murray Karen F. , Molleston Jean P. , Scheimann Ann , Xanthakos Stavra A. , Behling Cynthia A. , Hertel Paula , Nilson Jamie , Neuschwander-Tetri Brent A. , Tonascia James , Vos Miriam B. ,   for the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN)
Published: December 2023

Background:
Pediatric metabolic-associated fatty liver disease (MAFLD) is a global health problem, with lifestyle modification as its major therapeutic strategy. Rigorous characterization of dietary content on MAFLD in children is lacking. We hypothesized an objectively measured healthier diet would positively modulate MAFLD.

Methods:
Diet was assessed using the Nutrition Data System for Research in children enrolled from 10 tertiary clinical centers to determine the Healthy Eating Index (HEI, 0–100) and individual food components.

Results:
In all, 119 children were included (13.3 ± 2.7 y), 80 (67%) male, 67 (18%) White, and 90 (76%) Hispanic, with an average body mass index Z-score of 2.2 ± 0.5. Diet was classified as low HEI < 47.94 (n = 39), mid HEI ≥ 47.94 and < 58.89 (n = 41), or high HEI ≥ 58.89 (n=39). Children with high HEI (healthier diet) had lower body weight (p = 0.005) and more favorable lipids. Mean serum triglycerides for low, mid, and high HEI were 163, 148, and 120 mg/dL, respectively; p = 0.04 mid versus high, p = 0.01 low versus high. Mean HDL was 38, 41 and 43 mg/dL; p = 0.02 low vs high. Less severe steatosis was noted with added sugar ≤ 10% of calories (p = 0.03). Higher lobular inflammation is associated with a higher percentage of calories from fat (OR (95% CI) = 0.95 (0.91–1.00), p = 0.04).

Conclusions:
In children with MAFLD, high HEI is associated with lower body weight and more favorable lipids, while added sugar and fat intake has individual histologic features. Differential consumption of major dietary components may modify both metabolic risk factors and histologic liver injury, highlighting the importance of objective diet assessments in children with MAFLD.
FAT4 loss initiates hepatocarcinogenesis through the switching of canonical to noncanonical WNT signaling pathways
Authors: Huang Fung-Yu , Wong Danny Ka-Ho , Mak Lung-Yi , Cheung Tan-To , Zhang Sai-Sai , Chau Hau-Tak , Hui Rex Wan-Hin , Seto Wai-Kay , Yuen Man-Fung 
Published: December 2023

Background:
Mutation and downregulation of FAT atypical cadherin 4 (FAT4) are frequently detected in HCC, suggesting a tumor suppressor role of FAT4. However, the underlying molecular mechanism remains elusive.

Methods:
CRISPR-Cas9 system was used to knockout FAT4 (FAT4-KO) in a normal human hepatic cell line L02 to investigate the impact of FAT4 loss on the development of HCC. RNA-sequencing and xenograft mouse model were used to study gene expression and tumorigenesis, respectively. The mechanistic basis of FAT4 loss on hepatocarcinogenesis was elucidated using in vitro experiments.

Results:
We found that FAT4-KO disrupted cell-cell adhesion, induced epithelial-mesenchymal transition, and increased expression of extracellular matrix components. FAT4-KO is sufficient for tumor initiation in a xenograft mouse model. RNA-sequencing of FAT4-KO cells identified PAK6-mediated WNT/β-catenin signaling to promote tumor growth. Suppression of PAK6 led to β-catenin shuttling out of the nucleus for ubiquitin-dependent degradation and constrained tumor growth. Further, RNA-sequencing of amassed FAT4-KO cells identified activation of WNT5A and ROR2. The noncanonical WNT5A/ROR2 signaling has no effect on β-catenin and its target genes (CCND1 and c-Myc) expression. Instead, we observed downregulation of receptors for WNT/β-catenin signaling, suggesting the shifting of β-catenin-dependent to β-catenin-independent pathways as tumor progression depends on its receptor expression. Both PAK6 and WNT5A could induce the expression of extracellular matrix glycoprotein, laminin subunit alpha 4. Laminin subunit alpha 4 upregulation in HCC correlated with poor patient survival.

Conclusions:
Our data show that FAT4 loss is sufficient to drive HCC development through the switching of canonical to noncanonical Wingless-type signaling pathways. The findings may provide a mechanistic basis for an in-depth study of the two pathways in the early and late stages of HCC for precise treatment.
Neonatal cholestasis in children with Alpha-1-AT deficiency is a risk for earlier severe liver disease with male predominance
Authors: Teckman Jeffrey , Rosenthal Philip , Ignacio Rosalinda V. , Spino Cathie , Bass Lee M. , Horslen Simon , Wang Kasper , Magee John C. , Karpen Saul , Asai Akihiro , Molleston Jean P. , Squires Robert H. , Kamath Binita M. , Guthery Stephen L. , Loomes Kathleen M. , Shneider Benjamin L. , Sokol Ronald J. ,   for the ChiLDReN (Childhood Liver Disease Research Network)
Published: December 2023

Background:
Our objective was to better understand the natural history and disease modifiers of Alpha-1-antitrypsin deficiency (AATD), a common genetic liver disease causing hepatitis and cirrhosis in adults and children. The clinical course is highly variable. Some infants present with neonatal cholestasis, which can resolve spontaneously or progress to cirrhosis; others are well in infancy, only to develop portal hypertension later in childhood.

Methods:
The Childhood Liver Disease Research Network has been enrolling AATD participants into longitudinal, observational studies at North American tertiary centers since 2004. We examined the clinical courses of 2 subgroups of participants from the several hundred enrolled; first, those presenting with neonatal cholestasis captured by a unique study, enrolled because of neonatal cholestasis but before specific diagnosis, then followed longitudinally (n=46); second, separately, all participants who progressed to liver transplant (n=119).

Results:
We found male predominance for neonatal cholestasis in AATD (65% male, p=0.04), an association of neonatal gamma-glutamyl transpeptidase elevation to more severe disease, and a higher rate of neonatal cholestasis progression to portal hypertension than previously reported (41%) occurring at median age of 5 months. Participants with and without preceding neonatal cholestasis were at risk of progression to transplant. Participants who progressed to liver transplant following neonatal cholestasis were significantly younger at transplant than those without neonatal cholestasis (4.1 vs. 7.8 years, p=0.04, overall range 0.3–17 years). Neonatal cholestasis had a negative impact on growth parameters. Coagulopathy and varices were common before transplant, but gastrointestinal bleeding was not.

Conclusions:
Patients with AATD and neonatal cholestasis are at risk of early progression to severe liver disease, but the risk of severe disease extends throughout childhood. Careful attention to nutrition and growth is needed.
A review of posterior chamber phakic intraocular lenses
Authors: Reinstein Dan Z. , MacGregor Cheryl , Archer Timothy J. , Gupta Ruchi , Potter Joseph G. 
Published: December 2023

Purpose of review
Posterior chamber phakic intraocular lenses (pIOLs) are increasing in popularity as a viable alternative to laser refractive surgery. The purpose of this review is to evaluate the recent updates to pIOLs and to assess the advancements and safety of the procedure.

Recent findings
Accurate lens sizing is the key determinant to suitable vault prediction, advancements to sizing formulae including the use of very high frequency (VHF) digital ultrasound and the application of artificial intelligence and machine learning has led to improved vault prediction and safety. The introduction of the central aquaport has been shown to reduce the formation of cataract and is now adopted in most myopic pIOLs. Recently published studies have demonstrated that pIOLs have an excellent safety profile with no increased risk of retinal detachment or endothelial cell loss. Advancements have led to the introduction of extended depth of focus pIOLs for the correction of presbyopia, further research is required to evaluate the efficacy of new lens designs.

Summary
pIOL surgery is experiencing traction with improved lens design and increased lenses choices such as larger optical zone and presbyopic options. Accuracy of implantable collamer lens sizing is paramount to the safety and clinical outcomes, greater predictability is likely to encourage more posterior chamber pIOL users due to fewer sizing related complications.
Uniform Granular Pigmentation as a Novel Dermoscopic Feature of Drug Reaction: A Cross-Sectional Study
Authors: Lu Li-Xia , Zhao Shuang , Chen Ming-Liang , Chen Xiang , Su Juan 
Published: December 2023

Objective:
In clinical practice, black-brown-gray pigment granules are common under dermoscopy. However, little is known about their clinical significance. We conducted this study to investigate the relationship between dermoscopy features and their representative pathological features.

Methods:
A cross-sectional study was conducted by searching clinical database in Xiangya Hospital, Central South University, from August 2017 to August 2022. Patients with full information on pigment granules and demographic and pathological findings were entered. Cases were reviewed for information regarding pathological and dermoscopic patterns. Fisher exact test was used to examine the correlation between individual histologic variables and established diagnoses. The depth of pigment granules showed a nonnormal distribution and was analyzed using a nonparametric test.

Results:
In total, data from 83 patients were included in this analysis. The presence of pigment granules under dermoscopy significantly indicated destruction of basal cells or pigment incontinence (91.5%, 76/83). The pigment granules within lesions were divided into uniform and nonuniform patterns with respect to their size, color, and distribution. Uniform granular pigmentation was more likely to be associated with eosinophils (numerous or in aggregates, P < 0.001) or perifollicular inflammatory infiltration in the dermis (P = 0.008). Notably, brown pigment granules (P = 0.024) and uniform granular pigmentation (P < 0.001) were more likely to be induced by medications.

Conclusion:
Uniform granular pigmentation under dermoscopy is a novel indicator of a drug reaction and necessitates a detailed inquiry.
Evaluating Airway Management in Patients With Trisomy 21 in the PICU and Cardiac ICU: A Retrospective Cohort Study
Authors: Wilsterman Eric J. , Nellis Marianne E. , Panisello Josep , Al-Subu Awni , Breuer Ryan , Kimura Dai , Krawiec Conrad , Mallory Palen P. , Nett Sholeen , Owen Erin , Parsons Simon J. , Sanders Ronald C. , Garcia-Marcinkiewicz Annery , Napolitano Natalie , Shults Justine , Nadkarni Vinay M. , Nishisaki Akira ,   for the National Emergency Airway Registry for Children (NEAR4KIDS) and Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network
Published: December 2023

OBJECTIVES:
Children with trisomy 21 often have anatomic and physiologic features that may complicate tracheal intubation (TI). TI in critically ill children with trisomy 21 is not well described. We hypothesize that in children with trisomy 21, TI is associated with greater odds of adverse airway outcomes (AAOs), including TI-associated events (TIAEs), and peri-intubation hypoxemia (defined as > 20% decrease in pulse oximetry saturation [Spo
2]).

DESIGN:
Retrospective database study using the National Emergency Airway Registry for Children (NEAR4KIDS).

SETTING:
Registry data from 16 North American PICUs and cardiac ICUs (CICUs), from January 2014 to December 2020.

PATIENTS:
A cohort of children under 18 years old who underwent TI in the PICU or CICU from in a NEAR4KIDS center. We identified patients with trisomy 21 and selected matched cohorts within the registry.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
We included 8401 TIs in the registry dataset. Children with trisomy 21 accounted for 274 (3.3%) TIs. Among those with trisomy 21, 84% had congenital heart disease and 4% had atlantoaxial instability. Cervical spine protection was used in 6%. The diagnosis of trisomy 21 (vs. without) was associated with lower median weight 7.8 (interquartile range [IQR] 4.5–14.7) kg versus 10.6 (IQR 5.2–25) kg (p < 0.001), and more higher percentage undergoing TI for oxygenation (46% vs. 32%, p < 0.001) and ventilation failure (41% vs. 35%, p = 0.04). Trisomy 21 patients had more difficult airway features (35% vs. 25%, p = 0.001), including upper airway obstruction (14% vs. 8%, p = 0.001). In addition, a greater percentage of trisomy 21 patients received atropine (34% vs. 26%, p = 0.004); and, lower percentage were intubated with video laryngoscopy (30% vs. 37%, p = 0.023). After 1:10 (trisomy 21:controls) propensity-score matching, we failed to identify an association difference in AAO rates (absolute risk difference –0.6% [95% CI –6.1 to 4.9], p = 0.822).

CONCLUSIONS:
Despite differences in airway risks and TI approaches, we have not identified an association between the diagnosis of trisomy 21 and higher AAOs.
The Pediatric Data Science and Analytics Subgroup of the Pediatric Acute Lung Injury and Sepsis Investigators Network: Use of Supervised Machine Learning Applications in Pediatric Critical Care Medicine Research
Authors: Heneghan Julia A. , Walker Sarah B. , Fawcett Andrea , Bennett Tellen D. , Dziorny Adam C. , Sanchez-Pinto L. Nelson , Farris Reid W. D. , Winter Meredith C. , Badke Colleen , Martin Blake , Brown Stephanie R. , McCrory Michael C. , Ness-Cochinwala Manette , Rogerson Colin , Baloglu Orkun , Harwayne-Gidansky Ilana , Hudkins Matthew R. , Kamaleswaran Rishikesan , Gangadharan Sandeep , Tripathi Sandeep , Mendonca Eneida A. , Markovitz Barry P. , Mayampurath Anoop , Spaeder Michael C. ,   on behalf of the Pediatric Data Science and Analytics (PEDAL) subgroup of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network
Published: December 2023

OBJECTIVE:
Perform a scoping review of supervised machine learning in pediatric critical care to identify published applications, methodologies, and implementation frequency to inform best practices for the development, validation, and reporting of predictive models in pediatric critical care.

DESIGN:
Scoping review and expert opinion.

SETTING:
We queried CINAHL Plus with Full Text (EBSCO), Cochrane Library (Wiley), Embase (Elsevier), Ovid Medline, and PubMed for articles published between 2000 and 2022 related to machine learning concepts and pediatric critical illness. Articles were excluded if the majority of patients were adults or neonates, if unsupervised machine learning was the primary methodology, or if information related to the development, validation, and/or implementation of the model was not reported. Article selection and data extraction were performed using dual review in the Covidence tool, with discrepancies resolved by consensus.

SUBJECTS:
Articles reporting on the development, validation, or implementation of supervised machine learning models in the field of pediatric critical care medicine.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Of 5075 identified studies, 141 articles were included. Studies were primarily (57%) performed at a single site. The majority took place in the United States (70%). Most were retrospective observational cohort studies. More than three-quarters of the articles were published between 2018 and 2022. The most common algorithms included logistic regression and random forest. Predicted events were most commonly death, transfer to ICU, and sepsis. Only 14% of articles reported external validation, and only a single model was implemented at publication. Reporting of validation methods, performance assessments, and implementation varied widely. Follow-up with authors suggests that implementation remains uncommon after model publication.

CONCLUSIONS:
Publication of supervised machine learning models to address clinical challenges in pediatric critical care medicine has increased dramatically in the last 5 years. While these approaches have the potential to benefit children with critical illness, the literature demonstrates incomplete reporting, absence of external validation, and infrequent clinical implementation.
Experimental and Computational Analysis of HIFU Thermal Ablation in Breast Cancer Cells: Monolayers vs. Spheroids
Authors: Badawe Heba , Harouz Jean Paul , Abu Kareem , Raad Petra , Ghali Kamel Abou , Kheir Wassim Abou , Khrariche Massoud 
Published: December 2023

AbstractObjectiveThe primary objective of our study was to investigate the efficiency of high intensity focused ultrasound (HIFU) ablation in two distinct cellular configurations, 2D monolayers and 3D spheroids of epithelial breast cancer cell lines. The study also compares empirical findings from experiments with results obtained through numerical simulations using a bioheat computational model. This comparison is intended to provide a comprehensive understanding of the acoustic energy conversion within the biological system during HIFU treatment.MethodsHIFU was applied to 2D and 3D cultured MDA-MB 231 and MCF7 epithelial breast cancer cell lines while systematically varying ultrasound intensity and duty cycle (DC) during sonication sessions of different durations. Temperature elevation was measured and the ablation percentage was calculated based on bright field and fluorescent imaging of the treated regions. Experimental results were validated through simulations of the ablation setup.ResultsUpon HIFU, spheroids exhibited a lower temperature increase (approximately 20 °C) when subjected to comparable acoustic intensities and duty cycles. The level of tumor ablation was highly influenced by DC, with higher DCs leading to greater ablation percentages. However, sonication duration had a minimal impact on the degree of ablation. Numerical simulations corroborated these observations, demonstrating uniform heat distribution within the cultured cells. At higher DCs and intensities, complete ablation of spheroids was achieved, whereas at lower levels, only the outermost layers exhibited ablation.ConclusionOur study reveals a significant disparity in the response of 2D monolayers and 3D spheroids to HIFU treatment. Specifically, tumor spheroids require lower temperature elevations for effective ablation, and their ablation percentage significantly increases with elevated DC.