bluuebunny/crossref_metadata_2025_split huggingface dataset:
Double-flanged polypropylene technique: 5-year results
Authors: Canabrava Sérgio , Carvalho Marina Santana 
Published: February 2023

Purpose:
To assess the long-term (5-year) results and complications of the double-flanged polypropylene technique in patients with capsular tension segment fixation, nonfoldable intraocular lens (IOL) scleral fixation, and foldable IOL scleral fixation.

Setting:
Santa Casa de Belo Horizonte and Centro Oftalmológico de Minas Gerais.

Design:
Prospective case series.

Methods:
Eyes that underwent treatment using the double-flanged polypropylene technique between September 2016 to September 2021 were included. LogMAR visual acuity was recorded, as well as complications such as long-term polypropylene resistance, conjunctival erosion, conjunctival inflammation, flange exposure, internalization, endophthalmitis, retinal detachment, and cystoid macular edema.

Results:
71 eyes of 61 patients were evaluated. The mean follow-up period for these eyes was 28.2 ± 14.3 (min: 4; max: 60; median: 26) months. 173 flanges were performed. 13 cases with sub-Tenon flanges (7.5%) were observed. 5 exposed flanges (2.89%), presented after a mean of 1.8 weeks postoperatively, were observed. 1 patient with large flanges presented with conjunctival inflammation and hyperemia. 2 late internalized flanges (1.1%) and 2 recently internalized flanges (1.1%) were observed. 3 eyes (4.22%) had retinal detachment. Moreover, cystoid macular edema was detected in 3 eyes (4.22%). No cases of endophthalmitis were observed.

Conclusions:
The double-flanged technique was proven to be stable when the correct technical procedure was followed. However, complications can be observed, especially with short scleral tunnels and in eyes where the flanges were not buried inside the sclera.
Predicting corneal cross-linking treatment efficacy with real-time assessment of corneal riboflavin concentration
Authors: Lombardo Marco , Bernava Giuseppe Massimo , Serrao Sebastiano , Roszkowska Anna Maria , Lombardo Giuseppe 
Published: February 2023

Purpose:
To assess predictability of tissue biomechanical stiffening induced by UV-A light-mediated real-time assessment of riboflavin concentration during corneal crosslinking (CXL) of human donor tissues.

Setting:
Studio Italiano di Oftalmologia, Rome, Italy.

Design:
Laboratory study.

Methods:
20 sclerocorneal tissues were randomly stratified to undergo CXL with either the epithelium intact (n = 12) or removed (n = 8). Samples underwent corneal soaking with 0.22% riboflavin formulation (RitSight) with dosing time of t = 10 minutes and t = 20 minutes in epithelium-off and epithelium-on protocols, respectively. All tissues underwent 9-minute UV-A irradiance at 10 mW/cm2 using theranostic device (C4V CHROMO4VIS). The device used controlled UV-A light irradiation to induce both imaging and treatment of the cornea, providing a real-time measure of corneal riboflavin concentration and treatment efficacy (ie, theranostic score) during surgery. Tissue biomechanics were assessed with an air-puff device (Corvis), which was performed before and after treatment. A 3-element viscoelastic model was developed to fit the corneal deformation response to air-puff excitation and to calculate the mean corneal stiffness parameter (kc).

Results:
Significant corneal tissue stiffening (P < .05) was induced by the theranostic UV-A device in either CXL treatment protocol. Significant correlation was found between the theranostic score and the increase in kc (R = 0.75; P = .003). The score showed high accuracy (94%) and precision (94%) to predict correctly samples that had improved tissue biomechanical strengthening.

Conclusions:
Real-time assessment of corneal riboflavin concentration provided a predictive and precise approach for significant improvement of tissue strength on individual corneas, regardless of CXL treatment protocol.
Sirolimus Early Treatment in Vascular Anomalies Leads to a Better Response
Authors: Triana Paloma , Díez-Sebastián Jesús , Rodriguez-Laguna Lara , Martinez-Glez Victor , Lopez-Gutierrez Juan Carlos 
Published: February 2023

Objectives:
Sirolimus has become a relevant drug in the treatment of vascular anomalies, initially relegated to rescue therapy for refractory lesions but more recently has become first line. Our objective is to determine when it is best to start sirolimus treatment.

Methods:
A retrospective review of patients with vascular anomalies treated with sirolimus during a 9-year period was performed. The variables analyzed included subtype of vascular anomaly, age at the start of treatment, sirolimus dosage and levels, response, and duration of treatment among others.

Results:
One hundred twenty-two patients were included and classified according to ISSVA in: tumor (7), lymphatic malformation (60), venous malformation (16), combined malformations (18), associated overgrowth (8), and others (15). Overall response was positive in 90.8%. Median duration of treatment was 32 months (0–116). Response was not influenced by dosage or levels, neither by the subtype of vascular anomaly, location, extension, symptoms, genetic testing nor previous treatments. However, the lower the age of starting sirolimus, the better the response, mainly under 5 years of age (P = 0.004). At 6 months, 67% of patients had responded while at 12 months >84% did. By age, patients <5 years showed positive response at a median time of 2 months, compared to >5 months from older patients. Time until a positive response was not influenced by subtype or severity.

Conclusion:
Overall response to sirolimus was good and most patients responded irrespective of their severity in location, extension or symptoms. Patients <5 years old respond better and faster making our goal to attempt for an early treatment.
Developing a Genital Training Associate Program
Authors: Zorn Jennifer 
Published: February 2023

Abstract
Genitourinary training associates (GTAs) are individuals educated to teach medical learners invasive exams and procedures using their own body. Through specified protocols, the GTA teaches exam techniques to students in a supportive environment while giving feedback to the learner to optimize skill acquisition. Additionally, this experience can teach best practices for future provider-patient communication. To help ensure access to GTAs for medical learners, physician assistant (PA) programs should consider developing a GTA training program at their institution. The purpose of this article is to outline the necessary steps to educate GTAs and develop a GTA training program.
Prognostic Value of the Radiomics-Based Model in the Disease-Free Survival of Pretreatment Uveal Melanoma: An Initial Result
Authors: Su Yaping , Xu Xiaolin , Wang Fang , Zuo Panli , Chen Qinghua , Wei Wenbin , Xian Junfang 
Published: February 2023

Objective
The aim of this study was to develop a pretreatment magnetic resonance imaging (MRI)–based radiomics model for disease-free survival (DFS) prediction in patients with uveal melanoma (UM).

Methods
We randomly assigned 85 patients with UM into 2 cohorts: training (n = 60) and validation (n = 25). The radiomics model was built from significant features that were selected from the training cohort by applying a least absolute shrinkage and selection operator to pretreatment MRI scans. Least absolute shrinkage and selection operator regression and the Cox proportional hazard model were used to construct a radiomics score (rad-score). Patients were divided into a low- or a high-risk group based on the median of the rad-score. The Kaplan-Meier analysis was used to evaluate the association between the rad-score and DFS. A nomogram incorporating the rad-score and MRI features was plotted to individually estimate DFS. The model's discrimination power was assessed using the concordance index.

Results
The radiomics model with 15 optimal radiomics features based on MRI performed well in stratifying patients into the high- or a low-risk group of DFS in both the training and validation cohorts (log-rank test, P = 0.009 and P = 0.02, respectively). Age, basal diameter, and height were selected as significant clinical and MRI features. The nomogram showed good predictive performance with concordance indices of 0.741 (95% confidence interval, 0.637–0.845) and 0.912 (95% confidence interval, 0.847–0.977) in the training and validation cohorts, respectively. Calibration curves demonstrated good agreement.

Conclusion
The developed clinical-radiomics model may be a powerful predictor of the DFS of patients with UM, thereby providing evidence for preoperative risk stratification.
Quantitative Study of Vertebral Body and Paravertebral Muscle Degeneration Based on Dual-Energy Computed Tomography: Correlation With Bone Mineral Density
Authors: Liu Zhenghua , Zhang Yuting , Huang Dageng , Ma Xiaowen , Duan Yaqing , Jiang Yonghong 
Published: February 2023

Objectives
This study aimed to quantify the degeneration of the vertebral body and paravertebral muscles using dual-energy computed tomography (DECT) and study its relationship with osteoporosis.

Methods
A total of 130 patients with chronic low back pain were included in this study, and DECT scanning of the lumbar region was undertaken prospectively. By placing a standard quantitative computed tomography corrected phantom under the waist during the DECT procedure, bone mineral density (BMD) and the following quantitative parameters were obtained: calcium density (CaD), vertebral fat fraction (VFF), psoas major area, psoas major fat fraction, erector spinalis area, and erector spinalis fat fraction (ESFF). Independent sample t test and 1-way analysis of variance were used between different age-BMD groups. Pearson test was applied to determine correlations for all measurements, and a mathematical model of BMD was established through regression analysis.

Results
Calcium density, VFF, psoas major area, psoas major fat fraction, erector spinalis area, and ESFF were significantly different among the age-BMD groups (P < 0.05), and BMD was significantly correlated with these parameters (P < 0.05). Calcium density, VFF, and ESFF were included in the BMD regression equation: BMD = 69.062 + 11.637 × CaD − 1.018 × VFF − 0.726 × ESFF (R
2 = 0.860, F = 125.979, P < 0.001).

Conclusions
Degeneration of the vertebral body and paravertebral muscles can be quantitatively analyzed using DECT, and CaD, VFF, and ESFF were independent influencing factors of BMD.
Physical Performance Decline During the Early Posttransplantation Period Affects Survival After Living Donor Liver Transplantation
Authors: Kim Deok-Gie , Hwang Shin , Lee Kwang-Woong , Choi Gyu-seong , You Young Kyoung , Ryu Je Ho , Kim Bong-Wan , Nah Yang Won , Kim Dong-Sik , Cho Jai Young , Kang Koo Jeong , Hong Geun , Yu Hee Chul , Ju Man ki , Suh Suk-Won , Kim Kwan Woo , Choi Dongho , Jeong Jaehong , Choi Soo Jin Na , Moon Ju Ik , Lee Jae Geun , Kim Myoung soo , Choi Donglak , Joo Dong Jin 
Published: February 2023

Background.
Patient physical performance has been emphasized in liver transplant recipients; however, evidence for living donor liver transplantation (LDLT) patients is lacking. This study investigated the impact of physical performance decline during the early posttransplantation period on survival and risk factors for this decline in LDLT recipients.

Methods.
From national registry data, 2703 LDLT patients were divided into 2 groups based on the change in their Karnofsky performance status (KPS) between 1 and 6 mo posttransplantation: declined KPS (n = 188) and control (n = 2515). Multivariable analyses were conducted to control for confounders, including posttransplantation complications.

Results.
Estimated 5-y patient survival rates were 91.6% in the declined KPS group and 96.3% in the control group, favoring the latter (P = 0.003). The survival hazard of KPS decline was significant in a baseline covariates-adjusted Cox model (hazard ratio [HR], 2.60; 95% confidence interval [CI], 1.37-4.95) and an adjusted model accounting for posttransplantation complications (HR, 3.38; 95% CI, 1.70-6.72). In subgroup analyses, KPS decline independently reduced survival in patients without complications (HR, 3.95; 95% CI, 1.67-9.34), and the trend was similar in patients with complications, although significance was marginal (HR, 3.02; 95% CI, 0.98-9.27). We found that only posttransplantation complications, such as rejection, infection, bile duct complication, and vascular complication, were significant risk factors for KPS decline after LDLT.

Conclusions.
Physical performance decline during the early posttransplantation period independently reduced survival rates, and posttransplantation complications were the only significant risk factors for physical performance decline in LDLT recipients.
Development and Validation of an Alpha-Fetoprotein Tumor Burden Score Model to Predict Post-Recurrence Survival among Patients with Hepatocellular Carcinoma
Authors: Ding Hong-Fan , Yang Tian , Lv Yi , Zhang Xu-Feng , Pawlik Timothy M ,   and the International Hepatocellular Carcinoma Study Group
Published: February 2023

Background:
To establish a prognostic model to predict post-recurrence survival (PRS) probability after initial resection of hepatocellular carcinoma (HCC).

Study Design:
Patients with recurrent HCC after curative resection were identified through a multi-center consortium (training cohort, TC); data were from a separate institution was utilized as validation cohort (VC). The alpha-fetoprotein (AFP)-tumor burden score (ATS) was defined as the distance from the origin on a three-dimensional Cartesian coordinate system that incorporated 3 variables: largest tumor diameter (x-axis), number of tumors (y-axis) and ln AFP (z-axis). ATS was calculated using the Pythagorean theorem: [ATS

2

= (largest tumor diameter)
2

+(number of tumors)
2

+(ln AFP)
2
]. ATSd and ATSr represent ATS at time of initial diagnosis and at time of recurrence, respectively. The final model was “ATS
m
= ATS

d

+4×ATS

r
”. Predictive performance and discrimination of ATS model were evaluated and compared with traditional staging systems.

Results:
The ATS model demonstrated strong predictive performance to predict PRS in both the TC (AUC 0.70) and VC (AUC 0.71). An ATS-based nomogram was able to stratify patients accurately into low- and high-risk categories relative to PRS (TC: ATSm≤27, 74.9 mon vs. ATSm≥28, 23.3 mon; VC: ATSm≤27, 59.4 mon vs. ATSm≥28, 15.1 mon; both p<0.001). The ATS model predicted PRS among patient undergoing curative or non-curative treatments of HCC recurrence (both p<0.05). Of note, the ATS model outperformed the BCLC, CNLC, AJCC staging systems relative to 1-, 2-, 3-, 4- and 5-year PRS (AUC 0.70, vs. BCLC, AUC 0.50, vs. CNLC, AUC 0.54, vs. AJCC, AUC 0.51).

Conclusions:
The ATS model had excellent prognostic discriminatory power to stratify patients relative to PRS.
Gender Disparity in the Earliest Phase of Academic Surgical Training: An Area for Intervention
Authors: Zheng Hui , Al-Refaie Waddah , Chou Jiling , Galli Francesca , Lai Victoria , Felger Erin A 
Published: February 2023

Background:
To overcome persistent gender disparities in academic surgery, it is critical to examine the earliest phase of surgical training. This national study sought to assess whether gender disparities also existed among surgical interns, as a proxy for medical school research experience in both quantity and quality.

Method:
Using the 2021-2022 public information of 1,493 US-graduated categorical general surgery interns, a bibliometric evaluation was conducted to assess medical school research experience. Multivariable linear regressions with response log-transformed were performed to evaluate the impact of intern gender on 1) total number of peer-reviewed publications, 2) total impact factor (TIF), and 3) adjusted TIF based on authorship placement (aTIF). Back transformed estimates were presented.

Results:
52.3% were Female. Significant differences were observed in TIF (male 6.4 vs female 5.3, p=0.029), aTIF (male 10.8 vs female 8.7, p=0.035), gender concordance with senior authors (male 79.9% vs female 34.1%, p<0.001), Hirsch index (male 21.0 vs female 18.0, p=0.026), and the geographic region of their medical schools (p=0.036). Multivariable linear regressions revealed that female were associated with lower TIF (0.858, p=0.033) and aTIF (0.851, p=0.044). Due to a significant gender-by-region interaction, adjusted pairwise comparisons showed that male in the Northeast had approximately 70% higher TIF (1.708, p=0.003) and aTIF (1.697, p=0.013) than female in the South.

Conclusion:
Gender disparities existed in the quality of research experience in the earliest phase of surgical training. These timely results call for additional interventions by the stakeholders of graduate medical education.
Mechanistic models to meet the challenge of climate change in plant–pathogen systems
Authors: Jiranek Juliana , Miller Ian F. , An Ruby , Bruns Emme , Metcalf C. Jessica E. 
Published: February 2023

Evidence that climate change will impact the ecology and evolution of individual plant species is growing. However, little, as yet, is known about how climate change will affect interactions between plants and their pathogens. Climate drivers could affect the physiology, and thus demography, and ultimately evolutionary processes affecting both plant hosts and their pathogens. Because the impacts of climate drivers may operate in different directions at different scales of infection, and, furthermore, may be nonlinear, abstracting across these processes may mis-specify outcomes. Here, we use mechanistic models of plant–pathogen interactions to illustrate how counterintuitive outcomes are possible, and we introduce how such framing may contribute to understanding climate effects on plant–pathogen systems. We discuss the evidence-base derived from wild and agricultural plant–pathogen systems that could inform such models, specifically in the direction of estimates of physiological, demographic and evolutionary responses to climate change. We conclude by providing an overview of knowledge gaps and directions for future research in this important area.
This article is part of the theme issue ‘Infectious disease ecology and evolution in a changing world’.
Triptolide ameliorates renal tubulointerstitial fibrosis through EZH2
Authors: Wang Yanzhe , Jing Ying , Huang Di , Wu Ming , Ye Chaoyang 
Published: February 2023

AbstractRenal fibrosis is the final pathological pathway of various kidney disease in progression to the end stage of renal failure. Recent studies showed that the histone methyltransferase enhancer of zeste homolog 2 (EZH2) is an important epigenetic regulator of renal fibrosis by promoting epithelial-mesenchymal transition (EMT) and activation of TGF-β/Smad3 signaling pathway in fibrotic kidneys. Triptolide is component extracted from radix tripterygium wilfordii, which provides renal benefits to patients with renal diseases in China. Recently, triptolide was identified as an inhibitor of EZH2. Thus, we hypothesized that triptolide inhibits renal fibrosis through EZH2. In this study, we found that triptolide reduced the deposition of extracellular matrix in the kidney of unilateral ureteral obstruction (UUO) mice. The anti-fibrotic effect of triptolide was further confirmed in TGF-β stimulated HK2 cells, a human renal epithelial cell line. Moreover, treatment of triptolide blocked the up-regulation of EZH2 in UUO kidneys and reduced the expression of EZH2 in TGF-β stimulated HK2 cells. Down-regulation of EZH2 by triptolide was correlated with reduced expression of EMT markers and phosphorylation of Smad3 in UUO kidneys and TGF-β stimulated HK2 cells. Finally, we showed that inhibition of EZH2 by 3-DZNep attenuated the inhibitory effect of triptolide on the expression of extracellular matrix protein, EMT markers and activation of Smad3 in TGF-β stimulated HK2 cells.In conclusion, triptolide inhibits renal tubulointerstitial fibrosis through EZH2 in obstructive kidneys.
Smartphone-based ear-EEG to study sound processing in everyday life
Authors: Hölle Daniel , Bleichner Martin G. 
Published: February 2023

AbstractIn everyday life, people differ in their sound perception and thus sound processing. Some people may be distracted by construction noise while others do not even notice. With smartphone-based mobile earelectroencephalography we can measure and quantify sound processing in everyday life by analyzing presented sounds and also naturally occurring ones. Twenty-four participants completed four controlled conditions in the lab (1h) and one condition in the office (3h). All conditions used the same paired-click stimuli. In the lab, participants listened to click tones under four different instructions: no task towards the sounds, reading a newspaper article, listening to an audio article, or counting a rare deviant sound. In the office recording, participants followed daily activities while they were sporadically presented with clicks, without any further instruction. In addition to the presented sounds, environmental sounds were recorded as acoustic features (i.e., loudness, power spectral density, sounds onsets). We found task-dependent differences in the auditory event-related potentials (ERPs) to the presented click sounds in all lab conditions, which underline that neural processes related to auditory attention can be differentiated with ear-EEG. In the office condition, we found ERPs comparable to some of the lab conditions. The N1 amplitude to the click sounds beyond the lab was dependent on the background noise, probably due to energetic masking. Contrary to our expectation, we did not find a clear ERP in response to the environmental sounds. Overall, we showed that smartphone-based ear-EEG can be used to study sound processing of well defined-stimuli in everyday life.
Proteome encoded determinants of protein sorting into extracellular vesicles
Authors: Waury Katharina , Gogishvili Dea , Nieuwland Rienk , Chatterjee Madhurima , Teunissen Charlotte E. , Abeln Sanne 
Published: February 2023

AbstractExtracellular vesicles (EVs) are membranous structures released by cells into the extracellular space and are thought to be involved in cell-to-cell communication. While EVs and their cargo are promising biomarker candidates, protein sorting mechanisms of proteins to EVs remain unclear. In this study, we ask if it is possible to determine EV association based on the protein sequence. Additionally, we ask what the most important determinants are for EV association. We answer these questions with explainable AI models, using human proteome data from EV databases to train and validate the model. It is essential to correct the datasets for contaminants introduced by coarse EV isolation workflows and for experimental bias caused by mass spectrometry. In this study, we show that it is indeed possible to predict EV association from the protein sequence: a simple sequence-based model for predicting EV proteins achieved an area under the curve of 0.77±0.01, which increased further to 0.84±0.00 when incorporating curated post-translational modification (PTM) annotations. Feature analysis shows that EV associated proteins are stable, polar, and structured with low isoelectric point compared to non-EV proteins. PTM annotations emerged as the most important features for correct classification; specifically palmitoylation is one of the most prevalent EV sorting mechanisms for unique proteins. Palmitoylation and nitrosylation sites are especially prevalent in EV proteins that are determined by very strict isolation protocols, indicating they could potentially serve as quality control criteria for future studies. This computational study offers an effective sequence-based predictor of EV associated proteins with extensive characterisation of the human EV proteome that can explain for individual proteins which factors contribute to their EV association.