bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bile acids differentially regulate longitudinal smooth muscle contractility in everted mouse ileum
Authors: Dike Peace N. , Soni Krishnakant G. , Chang Diana S. , Preidis Geoffrey A. 
Published: June 2024

AbstractBile acids regulate gastrointestinal motility by mechanisms that are poorly understood. Standard isolated tissue bath assays might not recapitulate in vivo physiology if contractile responses to certain bile acids require direct application to the intestinal mucosa. We sought to determine the feasibility of quantifying longitudinal smooth muscle contractile responses to bile acids from intact segments of everted mouse ileum. Ileum from adult female C57BL/6J mice was isolated, gently everted over a notched metal rod, and mounted in tissue baths. Individual bile acids and agonists of bile acid receptors were added to the baths, and longitudinal smooth muscle contractile responses were quantified by isometric force transduction. Ursodeoxycholic acid robustly increased contractile responses in a dose‐dependent manner. Deoxycholic acid stimulated contractility at low doses but inhibited contractility at high doses. Chenodeoxycholic acid, glycocholic acid, and lithocholic acid did not alter contractility. The dose‐dependent increase in contractility resulting from the application of ursodeoxycholic acid was recapitulated by INT‐777, an agonist of the Takeda G protein‐coupled receptor 5 (TGR5), and by cevimeline, a muscarinic acetylcholine receptor agonist. Agonists to the nuclear receptors farnesoid X receptor, glucocorticoid receptor, pregnane X receptor, vitamin D receptor, and to the plasma membrane epidermal growth factor receptor did not modify baseline contractile patterns. These results demonstrate that gentle eversion of intact mouse ileum facilitates the quantification of longitudinal smooth muscle contractile responses to individual bile acids. Prokinetic effects of ursodeoxycholic acid and low‐dose deoxycholic acid are replicated by agonists to TGR5 and muscarinic acetylcholine receptors.
Preliminary Efficacy of Topical Sildenafil Cream for the Treatment of Female Sexual Arousal Disorder
Authors: Johnson Isabella , Thurman Andrea Ries , Cornell Katherine A. , Hatheway Jessica , Dart Clint , Brainard C. Paige , Friend David R. , Goldstein Andrew 
Published: June 2024

OBJECTIVE:
To assess the efficacy of topical sildenafil cream, 3.6% among healthy premenopausal women with female sexual arousal disorder.

METHODS:
We conducted a phase 2b, exploratory, randomized, placebo-controlled, double-blind study of sildenafil cream. Coprimary efficacy endpoints were the change from baseline to week 12 in the Arousal Sensation domain of the SFQ28 (Sexual Function Questionnaire) and question 14 of the FSDS-DAO (Female Sexual Distress Scale—Desire, Arousal, Orgasm).

RESULTS:
Two hundred women with female sexual arousal disorder were randomized to sildenafil cream (n=101) or placebo cream (n=99). A total of 174 participants completed the study (sildenafil 90, placebo 84). Among the intention-to-treat (ITT) population, which included women with only female sexual arousal disorder and those with female sexual arousal disorder with concomitant sexual dysfunction diagnoses or genital pain, although the sildenafil cream group demonstrated greater improvement in the SFQ28 Arousal Sensation domain scores, there were no statistically significant differences between sildenafil and placebo cream users in the coprimary and secondary efficacy endpoints. An exploratory post hoc subset of the ITT population with an enrollment diagnosis of female sexual arousal disorder with or without concomitant decreased desire randomized to sildenafil cream reported significant increases in their SFQ28 Arousal Sensation domain score (least squares mean 2.03 [SE 0.62]) compared with placebo cream (least squares mean 0.08 [SE 0.71], P=.04). This subset achieved a larger mean improvement in the SFQ28 Desire and Orgasm domain scores. This subset population also had significantly reduced sexual distress and interpersonal difficulties with sildenafil cream use as measured by FSDS-DAO questions 3, 5, and 10 (all P≤.04).

CONCLUSION:
Topical sildenafil cream improved outcomes among women with female sexual arousal disorder, most significantly in those who did not have concomitant orgasmic dysfunction. In particular, in an exploratory analysis of a subset of women with female sexual arousal disorder with or without concomitant decreased desire, topical sildenafil cream increased sexual arousal sensation, desire, and orgasm and reduced sexual distress.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT04948151.
Posterior Interosseous Artery Adipofascial Flap for the Management of Distal Radioulnar Joint Osteoarthritis
Authors: Lovic Aleksandar , Pérez-Rodríguez Javier , Bolado-Gutiérrez Pedro 
Published: June 2024

The management of distal radioulnar joint (DRUJ) osteoarthritis in young and active patients remains challenging. The purpose of this study was to describe our experience with a vascularized tissue interposition arthroplasty, based on a posterior interosseous artery adipofascial flap. This procedure is a biological alternative to previous DRUJ arthroplasties for patients who demand a strong and stable wrist and forearm. In this group of patients, it is indicated in the setting of osteoarthritis with pain and pronosupination block, but without advanced degeneration of the bone stock and the soft tissue stabilizers. This procedure was performed in 20 patients (mean age: 46), with a mean follow-up of 31 months. Mean postoperative pronation, supination, wrist flexion, and extension improved from the preoperative range to 73.2 degrees, 69 degrees, 52.4 degrees, and 45 degrees, respectively. A marked improvement in pain was recorded (from 7 to 1.5 Visual Analog Scale), with 13 patients completely pain-free. The mean preoperative Quick Disabilities of the Arm, Shoulder, and Hand score was 65.1, and the mean postoperative Quick Disabilities of the Arm, Shoulder, and Hand score was 20.1. Most patients had returned to work and resumed their hobbies. The technique proved effective as an alternative for the management of DRUJ osteoarthritis in young patients with high functional demands.

Level of Evidence:
Level IV—therapeutic.
Mohs Micrographic Surgery for Invasive Melanoma Allows for Tissue Preservation Compared With Wide Local Excision: A Retrospective Cohort Study
Authors: Rames Melissa M. , Campbell Elliott , Asamoah Eucabeth , Trischman Thomas , Kumar Anagha Bangalore , Vidal Nahid Y. , Demer Addison 
Published: June 2024

BACKGROUND
While increasing evidence supports the safety and effectiveness of immunohistochemistry-assisted Mohs micrographic surgery (MMS) for superficially invasive melanoma, there is a paucity of the literature investigating its effect on final defect size.

OBJECTIVE
To evaluate the tissue sparing effect of MMS for melanoma.

MATERIALS AND METHODS
Three hundred and twenty-eight patients with early-stage (T1a/T1b) cutaneous melanomas treated with MMS from January 2008 to December 2018 were evaluated. Measured defect sizes after Mohs tumor extirpation were compared with anticipated defect size that would result from standard-margin wide local excision (WLE). Average actual versus anticipated defect areas were compared using a paired t-test (95% confidence intervals).

RESULTS
The following groups demonstrated a significantly smaller defect area for MMS-treated tumors when compared with anticipated standard-margin WLE defect: All tumors combined (13.8 cm2 vs 10.4 cm2, p < .001), tumors requiring 1 stage (13.6 cm2 vs 10.1 cm2,
p < .001), and tumors requiring 2 stages (13.2 cm2 vs 10.5 cm2, p = .004). The majority of patients (83.5%, n = 274) achieved clear margins with 1 stage.

CONCLUSION
Immunohistochemistry-assisted MMS for early-stage invasive melanoma is associated with smaller final defect size and overall tissue sparing effect compared with standard WLE margins.
Clinical Versus Histologic Margins for Cutaneous Squamous Cell Carcinoma: Comparing Outcomes for High-Risk Tumors Treated With Mohs Micrographic Surgery
Authors: Juhasz Margit L. W. , Rosenthal Amanda H. , Nguyen Tuyet A. , Gharavi Nima M. 
Published: June 2024

BACKGROUND
High-risk cutaneous squamous cell carcinoma (cSCC) is associated with poor clinical outcomes. Traditionally, preoperative clinical tumor size ≥2 cm, based on Brigham and Women's Hospital (BWH) staging criteria, is high risk.

OBJECTIVE
To compare outcomes of cSCC treated with Mohs micrographic surgery (MMS) with a preoperative size ≥2 cm (clinically ≥2 cm) versus cSCC with preoperative size <2 cm and postoperative defect size ≥2 cm (histologically ≥2 cm).

METHODS
Prospective data were collected from January 1, 2014, to December 31, 2020, on MMS cases for cSCC with a preoperative and/or postoperative size ≥2 cm. Clinical outcomes were followed until March 15, 2023. Data were analyzed using multivariate regression.

RESULTS
Three hundred thirty cases of MMS for cSCC were included. Cutaneous squamous cell carcinoma clinically ≥2 cm occurred more frequently in elderly patients; cSCC histologically ≥2 cm were more commonly located in the H region, required wider surgical margins, and more MMS stages to achieve clearance. There were no significant differences in rates of recurrence and metastasis between the groups.

CONCLUSION
These data suggest that postoperative (histologic) MMS defect size may allow for better risk stratification of high-risk cSCC and improved staging of cSCC.
Multiple Buttresses Reconstruction of Maxilla with Fibular Flap Using Computer-aided Design/Computer-aided Manufacturing after Maxillectomy
Authors: Kurosawa Koreyuki , Sato Naoko , Ohkoshi Akira , Harata Takayuki , Ishi Shinyo , Hayashi Masanobu , Imai Toshiro , Takamura Nariaki , Matsunaga Hiromu , Imai Yoshimichi 
Published: June 2024

Background:
The maxilla comprises horizontal and vertical buttresses, each with specific functions, supporting various organs, such as the eyes, nose, and oral cavity. Notably, they combine to form a three-dimensional structure, which enables the buttresses to provide their inherent support strength. However, reconstructing the maxilla after maxillectomy by assembling new buttresses is challenging. We successfully reconstructed all the buttresses crucial for facial appearance and dental rehabilitation using a vascularized fibular flap.

Methods:
Four patients underwent maxillary buttress reconstruction with a fibular flap after total or subtotal maxillectomy. We used computer-aided design/computer-aided manufacturing digital technology to osteotomize the fibula into multiple segments and assemble them to reconstruct the maxillary buttresses. Each buttress was assembled based on a preoperative simulation.

Results:
All patients underwent immediate one-stage maxillary reconstruction. They had good maxillary buttress alignment and acquired good facial appearance, eye position, nasal airway, and prosthetically suitable maxillary alveolus ridge.

Conclusions:
The combination of computer-aided design/computer-aided manufacturing digital technology and surgical techniques has enabled novel maxillary reconstruction, providing great hope to patients experiencing facial disfigurement and loss of function after maxillectomy.
Breast Cancer Immunotherapy: A Clinical Review for the Plastic Surgeon
Authors: Heron Matthew J. , Zhu Katherine J. , Zhu Lily , Khong Jeffrey , Mundy Lily R. , Habibi Mehran , Broderick Kristen P. 
Published: June 2024

Background:
Immunotherapy has transformed breast cancer management. However, it can be challenging to remain familiar with the adverse events, contraindications, and perioperative recommendations for each agent.

Methods:
We used FDALabel to identify all Food and Drug Administration–approved immunotherapies indicated for the treatment of breast cancer. We extracted details regarding warnings and precautions, indications, and adverse events from each package insert.

Results:
We identified nine immunotherapies belonging to three classes: anti-human epidermal growth factor receptor 2 (HER2) agents, anti-programmed cell death protein 1 (PD-1) agents, and anti-trophoblast cell-surface antigen 2 (TROP-2) agents. Cardiotoxicity, including heart failure and cardiomyopathy, was common among those receiving anti-HER2 agents, and hypothyroidism was common among patients receiving the anti-PD-1 agent. The anti-TROP-2 agent was associated with diarrhea and neutropenia. Given the adverse event profile for each drug, we recommend preoperative evaluation components, including transthoracic echocardiography, liver function tests, and thyroid panels. We also indicate here which immunotherapies raise concern for venous thromboembolism, hematoma, and infection.

Conclusions:
Using data from clinical trials, we recommend a preoperative evaluation tailored to the immunotherapeutic regimen of individual patients.
Analysis of Treatment Discontinuation in Orthokeratology: Studying Efficacy, Safety, and Patient Adherence Over Six Months
Authors: Sánchez-García Alicia , Molina-Martin Ainhoa , Ariza-Gracia Miguel Ángel , Piñero David P. 
Published: June 2024

Purpose:
This study aimed to evaluate the efficacy, safety, and participant compliance of orthokeratology treatment for the correction of myopic refractive errors over a six-month prospective study and to define the potential reasons for early treatment discontinuation.

Methods:
A total of 32 participants with low-to-moderate myopia were fitted with the spherical model of corneal refractive therapy (CRT) orthokeratology lenses (Paragon Vision Sciences) and followed over six months, with specific attention to alterations in refractive error, corneal topography, and epithelial thickness. Concurrently, participant feedback and reasons for any treatment discontinuation were documented.

Results:
Significant changes in refractive error and in corneal topography were observed, with approximately 50% of the refractive error being corrected on the first night of use and 100% by the first two weeks (P<0.001). Central epithelial thickness experienced substantial thinning, reducing to 15.65±4.49 μm (67.38%) (P<0.001) after 6 months of lens use. Six participants withdrew from this study for varied reasons, including unmet visual expectations and difficulty adhering to the lens-wearing regimen. Notably, the dropout group exhibited higher baseline low-order aberrations and less prolate corneas than those who persisted with the treatment (P<0.05).

Conclusions:
Orthokeratology with CRT is efficacious and safe for the correction of low-to-moderate myopia in adults, but a portion of patients discontinue the treatment in the first 6 months of contact lens wear. Special care should be taken when recommending orthokeratology in patients with higher levels of myopia and corneas with less prolate shape, providing more realistic expectations and even changing to dual axis or more sophisticated designs.
Comparative Analysis of Endothelial Cell Density and Central Thickness of Corneas Used for Endothelial Keratoplasty Procedures Using Various Storage Solutions
Authors: Ramini Abhishek , Titus Michael S. , Sawant Onkar B. 
Published: June 2024

Purpose:
The goal of this study was to evaluate the effect of various Food and Drug Administration–approved storage solutions on endothelial cell density (ECD) and central corneal thickness (CCT).

Method:
We analyzed 6220 tissues used for endothelial keratoplasty procedures between January 2022 and June 2023 that were stored in either Life4°C, Optisol-GS, Kerasave, or Eusol-C under hypothermic conditions. We analyzed preprocessing CCT, success rate of meeting surgeon's Descemet stripping automated endothelial keratoplasty (DSAEK) thickness preferences, and preprocessing and postprocessing ECD. Results were analyzed using one-way analysis of variance, followed by multiple pairwise comparisons using the Tukey test.

Results:
Mean preprocessing CCT was significantly lower in the Life4°C group (532 μm) than in Optisol-GS (549 μm), Kerasave (582 μm), and Eusol-C (589 μm) groups (all P < 0.0001). Preprocessing CCT in the Optisol-GS group was significantly lower than in Kerasave and Eusol-C groups (F (3, 3273) = 153.1, all P < 0.0001). Success rate of meeting surgeon DSAEK preferences was statistically similar among all 4 groups. Preprocessing ECD of the Kerasave group (2821 cells/mm2) was numerically higher than of the Eusol-C (2791 cells/mm2), Life4°C (2759 cells/mm2), and Optisol-GS (2768 cells/mm2) groups (P = 0.3232, 0.0004, and 0.0015, respectively).

Conclusions:
Corneal tissues stored in Kerasave and Eusol-C are significantly thicker than those in Life4°C and Optisol-GS. However, the success rate of meeting surgeon DSAEK preferences is similar among all 4 storage solutions.
Online interpretable dynamic prediction models for clinically significant posthepatectomy liver failure based on machine learning algorithms: a retrospective cohort study
Authors: Jin Yuzhan , Li Wanxia , Wu Yachen , Wang Qian , Xiang Zhiqiang , Long Zhangtao , Liang Hao , Zou Jianjun , Zhu Zhu , Dai Xiaoming 
Published: June 2024

Background:
Posthepatectomy liver failure (PHLF) is the leading cause of mortality in patients undergoing hepatectomy. However, practical models for accurately predicting the risk of PHLF are lacking. This study aimed to develop precise prediction models for clinically significant PHLF.

Methods:
A total of 226 patients undergoing hepatectomy at a single center were recruited. The study outcome was clinically significant PHLF. Five preoperative and postoperative machine learning (ML) models were developed and compared with four clinical scores, namely, the MELD, FIB-4, ALBI, and APRI scores. The robustness of the developed ML models was internally validated using fivefold cross-validation (CV) by calculating the average of the evaluation metrics and was externally validated on an independent temporal dataset, including the area under the curve (AUC) and the area under the precision–recall curve (AUPRC). SHapley Additive exPlanations analysis was performed to interpret the best performance model.

Results:
Clinically significant PHLF was observed in 23 of 226 patients (10.2%). The variables in the preoperative model included creatinine, total bilirubin, and Child–Pugh grade. In addition to the above factors, the extent of resection was also a key variable for the postoperative model. The preoperative and postoperative artificial neural network (ANN) models exhibited excellent performance, with mean AUCs of 0.766 and 0.851, respectively, and mean AUPRC values of 0.441 and 0.645, whereas the MELD, FIB-4, ALBI, and APRI scores reached AUCs of 0.714, 0.498, 0.536, and 0.551, respectively, and AUPRC values of 0.204, 0.111, 0.128, and 0.163, respectively. In addition, the AUCs of the preoperative and postoperative ANN models were 0.720 and 0.731, respectively, and the AUPRC values were 0.380 and 0.408, respectively, on the temporal dataset.

Conclusion:
Our online interpretable dynamic ML models outperformed common clinical scores and could function as a clinical decision support tool to identify patients at high risk of PHLF preoperatively and postoperatively.
Progress in the radiologic diagnosis of idiopathic pulmonary fibrosis
Authors: Ledda Roberta Eufrasia , Marrocchio Cristina , Sverzellati Nicola 
Published: June 2024

Purpose of review
To discuss the most recent applications of radiological imaging, from conventional to quantitative, in the setting of idiopathic pulmonary fibrosis (IPF) diagnosis.

Recent findings
In this article, current concepts on radiological diagnosis of IPF, from high-resolution computed tomography (CT) to other imaging modalities, are reviewed. In a separate section, advances in quantitative CT and development of novel imaging biomarkers, as well as current limitations and future research trends, are described.

Summary
Radiological imaging in IPF, particularly quantitative CT, is an evolving field which holds promise in the future to allow for an increasingly accurate disease assessment and prognostication of IPF patients. However, further standardization and validation studies of alternative imaging applications and quantitative biomarkers are needed.
CECAL SLURRY AS AN ALTERNATIVE MODEL TO CECAL LIGATION AND PUNCTURE FOR THE STUDY OF SEPSIS-INDUCED CARDIOVASCULAR DYSFUNCTION
Authors: Delfrate Gabrielle , Albino Lucas Braga , Assreuy Jamil , Fernandes Daniel 
Published: June 2024

ABSTRACT
Sepsis is a life-threatening condition widely studied by animal models. Cecal ligation and puncture (CLP) is still regarded as the gold standard model for sepsis. However, CLP has limitations due to its invasiveness and variability. Cecal slurry (CS) model is a nonsurgical and thus less invasive alternative. However, the lack of standardization of the CS model in the literature limits its practical application. Additionally, it is not well studied whether CS model reproduces septic cardiovascular dysfunction in rats, which is a crucial issue in septic patients. Thus, this study aimed to standardize the CS model in Wistar rats and evaluate sepsis-induced cardiovascular dysfunction compared to CLP. Our results showed that CS model induced important features of sepsis cardiovascular dysfunction 24 h after its onset, such as hypotension, tachycardia, and decreased contractile response to vasoconstrictors both in vivo and ex vivo as well changes in renal blood flow. Increases in blood lactate, AST, ALT, creatinine, and urea indicated organ dysfunction. CS model also induced increased production of nitric oxide metabolites and bacterial spread to tissues. CS model causes less animal suffering, it is a nonsurgical model, and, more importantly, it replicates the cardiovascular dysfunction induced by sepsis with better homogeneity than CLP. Therefore, CS model serves as an alternative and possibly as a better model for sepsis research.