bluuebunny/crossref_metadata_2025 huggingface dataset:
STEM-01. DEVELOPMENT OF A HUMAN-SPECIFIC 3DIN VITRO PAEDIATRIC CEREBELLAR TUMOUR MODEL USING DECELLULARISED BRAIN AUTOPSY TISSUE
Authors: McCrorie Phoebe , Porter Harry , Diksin Mohammed , Moloney Cara , Grundy Richard , Rahman Ruman
Published: June 2024

BACKGROUND

Medulloblastoma (MB) and Atypical Teratoid/ Rhabdoid Tumours (ATRT) represent paediatric cerebellar tumours with a dismal prognosis. For ATRT in particular, 5-year survival remains at less than 32%. We have developed a 3D in vitro model termed ‘tumoursphere matrix’ which recapitulates in vivo crosstalk between tumour and reactive brain.

METHODS AND RESULTS

We co-cultured D283 (Group 3-MYC amplified MB) and BT12 (ATRT-MYC) cells with primary human cerebellar astrocytes within a PEGDA hydrogel containing decellularised cerebellar extracellular matrix (ECM) derived from non-disease human autopsy brain. Cerebellar ECM was extensively characterised, showing a significant reduction in cellular material whilst retaining ECM ligands. Reduction of DNA content to 174 ng/mg was corroborated by an absence of nuclei in immunohistochemical staining. Colorimetric assays indicated collagen and glycosaminoglycan retention in decellularised ECM, and Immunofluorescence confirmed retention of fibronectin, laminin and hyaluronic acid. Detection of all ECM ligands was cross-validated by Orbitrap-Secondary Ion Mass Spectrometry. A solubilised ECM/PEGDA hydrogel was used to coat an AggreWell™ plate. Primary human cerebellar astrocytes, D283 and BT12 cells were cultured as spheroids within the ECM/PEGDA hydrogel for 7 days with no significant decrease in cellular viability. Cytokine and Human Matrix Metalloproteinase (MMP) Antibody Arrays showed cytokine and MMP expression in all three cell lines was retained in the presence of ECM material. Furthermore, D283 and BT12 cells were co-cultured with primary astrocytes for 7 days prior to separation using fluorescence activated cell sorting to generate individual cell populations.

CONCLUSIONS

We have developed a 3D in vitro model which can co-culture cells for over 7 days, whilst recapitulating the in vivo tumour environment. RNA sequencing is currently in progress to identify differentially expressed genes in cerebellar tumour cells upon astrocytic and brain ECM crosstalk. We hypothesise that biochemical signalling underlying this communication will reveal putative therapeutic vulnerabilities.
STEM-06. THE ROLE OF SHH SIGNALING PATHWAY IN RETINOBLASTOMA INITIATION AND PROGRESSION
Authors: Liu Xiao , Murad Najiba , Pei Yanxin , Micklye McKayla Bridgette
Published: June 2024

BACKGROUND

Retinoblastoma is a rare childhood cancer of the retina that shows the biallelic loss of RB1 in nearly 95% of cases. It was reported that SHH pathway proteins, such as SHH, GLI1, and GLI2, are aberrantly high in human retinoblastoma, and high GLI2 expression is associated with aggressive clinicopathological features. Thus, we assessed whether activation of SHH pathway by overexpression of Gli2 or SMO induces the initiation of retinoblastoma.

METHODS

We generated a Cre-activated, Doxycycline (Dox)-controlled transgenic model to induce SMO or Gli2 expression in developing retina. In this transgenic mouse, expression of Smo or Gli2A is under the control of TRE, which permits temporal and spatial expression of Smo or Gli2A by administering/withdrawing doxycycline (DOX).

RESULTS

We fed the triple transgenic mice (Chx10-Cre/R26-LSL-rtTA/tetO-Smo or Chx10-Cre/R26-LSL-rtTA/tetO-Gli2A starting from E0 or P5. Our studies demonstrated that control littermates (Cre-) did not show any abnormalities, while mice with triple transgenes developed tumors in the bilateral eyes with 100% morbidity. The animals showed symptoms of leukocoria at P0-P3 or P25-p30 if the oncogenes were initiated at E0 or P5 respectively. The tumor cells were highly proliferative and expressed retina progenitor cell specific marker of Sox2, showing aberrant expression of pRB, CDK4/6, and CCND1.

CONCLUSIONS

Our results demonstrate that overexpressing Smo or Gli2 in Chx10+ cells induce rapid tumor formation in mouse retina. In future study, we plan to (i) investigate the impact of Shh pathway activation in RPCs on RB tumorigenesis within the context of Rb1 loss; (ii) define the molecular mechanisms underlying tumor initiation and progression; and (iii) evaluate whether targeting SHH pathway prevents or delays tumor initiation and progression using our Gli2-driven mouse model and patient-derived xenografts.
Dual role of proliferating cell nuclear antigen monoubiquitination in facilitating Fanconi anemia-mediated interstrand crosslink repair
Authors: Shah Ronak , Aslam Muhammad Assad , Spanjaard Aldo , de Groot Daniel , Zürcher Lisa M , Altelaar Maarten , Hoekman Liesbeth , Pritchard Colin E J , Pilzecker Bas , van den Berk Paul C M , Jacobs Heinz
Published: June 2024

The Fanconi anemia (FA) repair pathway governs repair of highly genotoxic DNA interstrand crosslinks (ICLs) and relies on translesion synthesis (TLS). TLS is facilitated by REV1 or site-specific monoubiquitination of proliferating cell nuclear antigen (PCNA) (PCNA-Ub) at lysine 164 (K164). A PcnaK164R/K164R but not Rev1−/− mutation renders mammals hypersensitive to ICLs. Besides the FA pathway, alternative pathways have been associated with ICL repair (1, 2), though the decision making between those remains elusive. To study the dependence and relevance of PCNA-Ub in FA repair, we intercrossed PcnaK164R/+; Fancg−/+ mice. A combined mutation (PcnaK164R/K164R; Fancg−/−) was found embryonically lethal. RNA-seq of primary double-mutant (DM) mouse embryonic fibroblasts (MEFs) revealed elevated levels of replication stress-induced checkpoints. To exclude stress-induced confounders, we utilized a Trp53 knock-down to obtain a model to study ICL repair in depth. Regarding ICL-induced cell toxicity, cell cycle arrest, and replication fork progression, single-mutant and DM MEFs were found equally sensitive, establishing PCNA-Ub to be critical for FA-ICL repair. Immunoprecipitation and spectrometry-based analysis revealed an unknown role of PCNA-Ub in excluding mismatch recognition complex MSH2/MSH6 from being recruited to ICLs. In conclusion, our results uncovered a dual function of PCNA-Ub in ICL repair, i.e. exclude MSH2/MSH6 recruitment to channel the ICL toward canonical FA repair, in addition to its established role in coordinating TLS opposite the unhooked ICL.
Systematic discrepancies in the delivery of political ads on Facebook and Instagram
Authors: Bär Dominik , Pierri Francesco , De Francisci Morales Gianmarco , Feuerriegel Stefan
Published: June 2024

Political advertising on social media has become a central element in election campaigns. However, granular information about political advertising on social media was previously unavailable, thus raising concerns regarding fairness, accountability, and transparency in the electoral process. In this article, we analyze targeted political advertising on social media via a unique, large-scale dataset of over 80,000 political ads from Meta during the 2021 German federal election, with more than 1.1 billion impressions. For each political ad, our dataset records granular information about targeting strategies, spending, and actual impressions. We then study (i) the prevalence of targeted ads across the political spectrum; (ii) the discrepancies between targeted and actual audiences due to algorithmic ad delivery; and (iii) which targeting strategies on social media attain a wide reach at low cost. We find that targeted ads are prevalent across the entire political spectrum. Moreover, there are considerable discrepancies between targeted and actual audiences, and systematic differences in the reach of political ads (in impressions-per-EUR) among parties, where the algorithm favor ads from populists over others.
Consequences of gene editing of PRLR on thermotolerance, growth, and male reproduction in cattle
Authors: Cuellar Camila J. , Amaral Thiago F. , Rodriguez‐Villamil Paula , Ongaratto F. , Martinez D. Onan , Labrecque Rémi , Losano João D. de Agostini , Estrada‐Cortés Eliab , Bostrom Jonathan R. , Martins Kyra , Rae D. Owen , Block Jeremy , Hoorn Quinn A. , Daigneault Bradford W. , Merriam Jonathan , Lohuis Michael , Dikmen Serdal , Bittar João H. J. , Maia Tatiane S. , Carlson Daniel F. , Larson Sabreena , Sonstegard Tad S. , Hansen Peter J.
Published: June 2024

Global warming is a major challenge to the sustainable and humane production of food because of the increased risk of livestock to heat stress. Here, the example of the prolactin receptor (PRLR) gene is used to demonstrate how gene editing can increase the resistance of cattle to heat stress by the introduction of mutations conferring thermotolerance. Several cattle populations in South and Central America possess natural mutations in PRLR that result in affected animals having short hair and being thermotolerant. CRISPR/Cas9 technology was used to introduce variants of PRLR in two thermosensitive breeds of cattle – Angus and Jersey. Gene‐edited animals exhibited superior ability to regulate vaginal temperature (heifers) and rectal temperature (bulls) compared to animals that were not gene‐edited. Moreover, gene‐edited animals exhibited superior growth characteristics and had larger scrotal circumference. There was no evidence for deleterious effects of the mutation on carcass characteristics or male reproductive function. These results indicate the potential for reducing heat stress in relevant environments to enhance cattle productivity.
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

Bile 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.
Effect of Infection Control Simulation Based on a Negative Pressure Isolation Room Using Mixed Reality
Authors: Kim Kyeng-Jin , Lee Joonyoung , Choi Moon-Ji
Published: June 2024

This study aimed to examine the effectiveness of an infection control simulation using mixed reality, comparing simulation fidelity with a high-fidelity mannequin (MN) group and problem-based learning with written cases group. This study used a three-group pretest-posttest quasi-experimental design. Two universities with similar curricula were conveniently selected, and a total of 72 nursing students were recruited. Participants were randomly assigned to three groups of 24 each. In the final analysis, there were 22 participants in the mixed reality groups, 21 in the mannequin groups, and 23 in the problem-based learning with written cases groups. Data were analyzed using descriptive statistics and the χ2, Kruskal-Wallis, and Wilcoxon signed rank tests. The mixed reality groups had a significantly positive effect on clinical reasoning ability and clinical competence than the problem-based learning with written cases groups, whereas the mannequin groups had a significantly positive effect on clinical competence than the problem-based learning with written cases groups. Mixed reality simulation is an appropriate simulation method that enhances learning immersion, satisfaction, and self-confidence in simulation. Additionally, it can substitute for mannequin simulation in terms of clinical reasoning ability and clinical competence. This study suggests that it is important to the various approaches in simulation fidelity to diversely enhance the competency of nursing students in simulation outcomes.
Hotspots and Global Trends of Nursing Research on Mobile Applications in Nursing From 2012 to 2023
Authors: Li Tao , Huang Tingting , Gao Jing
Published: June 2024

The rapid integration of mobile applications in healthcare has prompted an evolutionary change in nursing domain. This study aimed to systematically analyze the basic publication characteristics, research priorities, emerging trends, and thematic evolutions concerning mobile applications in nursing, providing an overview of the field's developmental trajectory and future directions. This was a descriptive bibliometric study. Data were collected on July 5, 2023, from the Web of Science database and analyzed by using the Bibliometrix package in R software. The search strategy yielded 417 documents authored by 1969 researchers, cited 12 595 references, and featured 1213 author keywords, spanning from 2012 to 2023. Research on mobile applications in nursing exhibited several key trends: (1) substantial collaboration among authors; (2) significant growth in the number of publications; (3) self-management was the most prominent hot topic; and (4) an evolution of research themes from general topics to a more specific focus on people-centered and problem-centered research. The corpus of literature pertaining to research on mobile applications within the nursing domain is anticipated to expand continually. Future research and practice in the nursing field are expected to benefit significantly from multidisciplinary collaboration and advancements in emerging technologies, including artificial intelligence.
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.

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

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.
Teaching Families How to Manage Diabetic Emergencies Using Their Children as Patient Simulators
Authors: Levy Arielle R. , Leo Harmine C. , Joseph Tatiana , Henderson Mélanie , Olivier Patricia , Shayan Yasaman , Buithieu Maria
Published: June 2024

Objectives

The aims of the study are to develop an insulin pump simulation curriculum using patients as simulators, to evaluate its effectiveness on knowledge, attitudes, and skills necessary for families to manage diabetic emergencies, and to identify ongoing gaps in care.

Methods

Our simulation curriculum developed using Kerns, consisted of 4 stations. A prospective simulation study was conducted at a pediatric tertiary care hospital with a convenience sample of children with type 1 diabetes on the insulin pump program and their families using patients as simulators and their parents as participants. The curriculum's success with developing competent skills was assessed using Kirkpatrick's 4-level evaluation model. Data from satisfaction questionnaires, performance gaps in emergency management, and postsimulation knowledge questionnaires were analyzed to identify ongoing gaps in care using a mixed methods approach.

Results

Among 70 families (169 participants), satisfaction was high (3.7–4.0/4.0) and confidence was increased (mean score 12 ± 0.03/12). Recurrent performance gaps across scenarios were found: misunderstandings about residual insulin during hypoglycemia (35%) and severe hypoglycemia with altered level of consciousness (22%), and failure to identify causes in 13% of simple and 11% of severe hypoglycemia scenarios and overtreating hypoglycemia with glucagon in a conscious patient in 14% of simple hypoglycemia scenarios. Postsimulation knowledge questionnaires revealed improvements in knowledge/management of simple hypoglycemia (mean score 87%), poor knowledge of pump parameters (mean score 56%), excellent knowledge of manipulating pump parameters to prevent emergencies (mean score 100%), and poor knowledge of basal rate concepts (mean score 19%).

Conclusions

Simulation using patient simulators improved management skills and confidence of families facing diabetic emergencies. Ongoing gaps in care were identified and used to enhance the current curriculum. Integrating simulation into insulin pump curricula can enhance patient self-care, safety, and be generalizable to other chronic-care patient-education programs. Future work should evaluate the impact of this curriculum on real-life events and patient outcomes.
A Contemporary Evaluation of the Centers for Medicare and Medicaid Services High-risk Indicators for Carotid Endarterectomy
Authors: Straus Sabrina , Barodi Batol , Zarrintan Sina , Willie-Permor Daniel , Vootukuru Nishita , Malas Mahmoud
Published: June 2024

Objective:

Compare stroke/death outcomes across carotid endarterectomy (CEA), transcarotid artery revascularization (TCAR), and transfemoral carotid artery stenting (TFCAS) using Centers for Medicare and Medicaid Services (CMS) high-risk criterion.

Background:

Existing literature has revealed inconsistencies with CMS risk guidelines. With recent approval for TCAR and TFCAS in standard-risk patients, an updated analysis of guidelines is needed.

Methods:

Data from the Vascular Quality Initiative (VQI) (2016–2023) on CEA, TFCAS, or TCAR patients were used. We used inverse probability of treatment weighting to compare in-hospital stroke/death rates across procedures for high-risk criteria: contralateral occlusion (CLO), prior CEA, CAS, radiation, neck surgery, moderate to severe CHF, severe COPD (on home O2), unstable angina, recent MI (<6 mo), and age (≥75 years-old).

Results:

A total of 199,050 patients were analyzed, of whom 122,737 (62%) patients underwent CEA, 50,095 (25%) TCAR, and 26,218 (13%) TFCAS. TCAR had lower odds of stroke/death compared with CEA in patients with CLO [aOR=0.73 (95% CI: 0.55–0.98], P=0.035] and radiation [aOR=0.44 (95% CI: 0.23–0.82), P=0.010]. Contrary to CMS criteria, CEA patients did not have higher stroke/death in patients with prior CEA, CAS, neck surgery, moderate to severe CHF, severe COPD, unstable angina, recent MI, or age (≥75) compared with TCAR and TFCAS.

Conclusions:

While CMS high-risk criteria have traditionally been recognized as contraindications for CEA, our study reveals inconsistencies—with CEA performing similarly to TCAR and significantly better than TFCAS in patients with prior CEA, moderate to severe CHF, recent MI, or age (≥75). As a result, the definition of high-risk criteria may warrant reconsideration.
An Analysis of Water Used and Wasted at Operating Room (OR) Scrub Sinks and Call to Action for Reducing Water Waste
Authors: Hu Carolyn J. , Reilly Margaret , Khan Imadh , Hoel Andrew W. , Sturgeon Cord , Ho Karen J.
Published: June 2024

Objective:

To model the volume of water used and wasted during wet scrubs at operating room (OR) scrub sinks and identify factors for reducing water waste.

Background:

Wasteful consumption of water by US healthcare systems has not been well characterized.

Methods:

This is a two-component observational study. The first was an observational study of handwashing practices and water usage at scrub sinks in the OR at a single medical center. The second component was a series of two anonymous surveys of surgeons and OR staff to assess hand scrub practices and perspectives. Data from both components were used to estimate the volume of water used and wasted annually at OR scrub sinks.

Results:

The median total volume of water wasted at OR scrub sinks for 34,554 cases over one year is 337,595.6 L (interquartile range 139,010.0;911,210.5). This represents approximately 34.2% of the total volume of water usage associated with wet scrubs (i.e.,water used during scrubbing and wasted after the conclusion of the scrub). Other pertinent findings are that attending surgeons and OR staff perform water scrubs in 25.9% of cases; there are significant differences in scrub type preferences among OR users; the median volume of water wasted in a single wet scrub at timer-controlled sinks is 10 L; and significantly more water is wasted at timer-controlled sinks than knee-operated sinks.

Conclusions:

OR wet scrubs are a source of enormous water waste. We identified scrub sink characteristics and OR user beliefs and behaviors as modifiable factors for water waste reduction. We encourage all institutions and OR users to carefully examine their facility characteristics and practices to implement plans that will conserve water without compromising patient safety.
Collaborative implementation science: a Can-SOLVE CKD case example
Authors: Allu Selina , Beaucage Mary , Donald Maoliosa , Escoto Manuel , Kappel Joanne , Morrin Louise , Soroka Steven D.
Published: June 2024

Research is critical for uncovering new and effective therapies for better health outcomes, yet there remains a significant lag between identifying evidence-based interventions and implementing them into practice. Research teams can often be experienced in evidence generation, but less so in evidence implementation, underscoring the need for more customized tools to support them in this latter step. The implementation stage can be especially challenging given how strategies must be tailored to the unique end users and contexts of a given intervention. Therefore, our patient-oriented kidney research network sought to create an “Implementation Toolkit” and “Pathway to Implementation” guide to help research teams and their operational and clinical partners in implementing their interventions. Importantly, the tools were created using input and feedback from diverse groups, including patient partners, implementation science experts, researchers, operational leaders, and policymakers, all of whom play role in supporting the implementation of health interventions. Our tools are widely applicable to diverse teams, regardless of the intervention or innovation being implemented.

Spanish abstract:

http://links.lww.com/IJEBH/A214
Bayesian cluster geographically weighted regression for spatial heterogeneous data
Authors: Draidi Areed Wala , Price Aiden , Thompson Helen , Hassan Conor , Malseed Reid , Mengersen Kerrie
Published: June 2024

Spatial statistical models are commonly used in geographical scenarios to ensure spatial variation is captured effectively. However, spatial models and cluster algorithms can be complicated and expensive. One of these algorithms is geographically weighted regression (GWR) which was proposed in the geography literature to allow relationships in a regression model to vary over space. In contrast to traditional linear regression models, which have constant regression coefficients over space, regression coefficients are estimated locally at spatially referenced data points with GWR. The motivation for the adaption of GWR is the idea that a set of constant regression coefficients cannot adequately capture spatially varying relationships between covariates and an outcome variable. GWR has been applied widely in diverse fields, such as ecology, forestry, epidemiology, neurology and astronomy. While frequentist GWR gives us point estimates and confidence intervals, Bayesian GWR enriches our understanding by including prior knowledge and providing probability distributions for parameters and predictions of interest. This paper pursues three main objectives. First, it introduces covariate effect clustering by integrating a Bayesian geographically weighted regression (BGWR) with a post-processing step that includes Gaussian mixture model and the Dirichlet process mixture model. Second, this paper examines situations in which a particular covariate holds significant importance in one region but not in another in the Bayesian framework. Lastly, it addresses computational challenges in existing BGWR, leading to enhancements in Markov chain Monte Carlo estimation suitable for large spatial datasets. The efficacy of the proposed method is demonstrated using simulated data and is further validated in a case study examining children’s development domains in Queensland, Australia, using data provided by Children’s Health Queensland and Australia’s Early Development Census.
Revisiting
Stygocapitella
(Annelida, Parergodrilidae) in Japan, with insights into their amphi-Pacific diversification
Authors: Hookabe Natsumi , Jimi Naoto , Fujimoto Shinta , Kajihara Hiroshi
Published: June 2024

Polychaetes are typically found in marine environments with limited species adapting to semi-terrestrial habitats. The genus
Stygocapitella
comprises interstitial polychaetes dwelling in sandy beach areas around or above the high-water line. Based on molecular data, previous studies suggested the presence of multiple cryptic species in some different localities in the world lumped together as
Stygocapitella subterranea
. In Japan, reports on
Stygocapitella
were scarce, with only one species having been documented 40 years ago at Ishikari Beach in Hokkaido by the name of
S. subterranea
. We revisited these earlier findings and uncovered the presence of two distinct species in
Stygocapitella
. One of these species is herein named
Stygocapitella itoi
sp. nov., while the other corresponds to
S. budaevae
, originally described from the Russian Far East.
Stygocapitella itoi
sp. nov. possesses a chaetal pattern similar to that of
S. australis
,
S. furcata
and
S. pacifica
but can be distinguished from the congeners by two characters: a slightly forked pygidium and forked chaetae consisting of two teeth and two outer prongs. Our multi-locus phylogenetic analysis showed close relationships across the Pacific Ocean in two separated lineages in the genus, suggesting ancient dispersal or allopatric speciation after vicariance events.
Prediction of individual differences in non-iridescent structural plumage colour from nanostructural periodicity and regularity
Authors: Hegyi Gergely , Laczi Miklós , Wacha András , Gyarmathy Helga , Klein Ákos , Rosivall Balázs , Sarkadi Fanni , Szabó Gyula , Török János
Published: June 2024

Non-iridescent structural plumage reflectance is a sexually selected indicator of individual quality in several bird species. However, the structural basis of individual differences remains unclear. In particular, the dominant periodicity of the quasi-ordered feather barb nanostructure is of key importance in colour generation, but no study has successfully traced back reflectance parameters, and particularly hue, to nanostructural periodicity, although this would be key to deciphering the information content of individual variation. We used matrix small-angle X-ray scattering measurements of intact, stacked feather samples from the blue tit crown to estimate the sex-dependence and individual variation of nanostructure and its effects on light reflectance. Measures of nanostructural periodicity successfully predicted brightness, ultraviolet chroma and also hue, with statistically similar effects in the two sexes. However, we also observed a lack of overall effect of the nanostructural inhomogeneity estimate on reflectance chromaticity, sex-dependent accuracy in hue prediction and strong sex-dependence in position estimation error. We suggest that reflectance attributes are modified by other feather structures in a sex-specific manner, and that within-individual variation in nanostructural parameters exists within or among feathers and this confounds the interpretation of structure–reflectance relationships at the plumage area level.