bluuebunny/crossref_metadata_2025_split huggingface dataset:
Geometric Wire-frame Fixation of Skin Grafting for Lip Reconstruction
Authors: Ishii Nobuaki , Akimoto Masataka , Ogawa Rei 
Published: September 2023

Summary:
Postoperative fixation is required for skin grafts on mobile sites. External wire-frame fixation technique has demonstrated a beneficial role for grafts in specific areas such as lips, eyelids, and fingers. Although this technique is sufficient in most cases, patients with psychosis fail to maintain the lip in resting position, which led us to consider using a more rigid fixation method, known as “Geometric wire-frame fixation.” Surgical technique included fixing a perimeter frame around skin graft similar to the conventional external wire-frame fixation. In addition, a geometric frame was prepared to divide the area of the graft geometrically. Then, it was placed on gauze to compress the grafted skin, and connected to the perimeter frame. In case 1, a 33-year-old man with a history of schizophrenia and presenting with flame burn injury sustained while attempting suicide was admitted. The scar on the lips was excised, and an external wire-frame fixation was performed. However, postoperative vigorous mouth movements caused incomplete survival of the skin graft. Geometric wire-frame fixation was performed in the next operation, and the graft fully survived. The patient in case 2 was a 62-year-old man who developed a facial scar contracture after chemical injury by sulfuric acid. We performed geometric wire-frame fixation with contracture release of the upper lip, and the skin graft was fully taken. The geometric wire-frame fixation method allows for rigid fixation of the skin graft and can be considered as a valuable option, especially for lip reconstruction in poorly compliant patients who are unable to maintain proper resting lips.
Neurologic impact of atrial fibrillation
Authors: Feldman Daniel R. , Zeitler Emily P. 
Published: September 2023

Purpose of review
Cognitive dysfunction is a complex condition that is becoming increasingly more prevalent. There has been growing acknowledgement that individuals with atrial fibrillation are at an increased risk of cognitive dysfunction beyond the association of age with both disorders. The purpose of this review is to explore the potential underlying mechanisms connecting atrial fibrillation and cognitive dysfunction and to examine the existing evidence for potential treatment options.

Recent findings
Many mechanisms have been proposed for the association between cognitive dysfunction and atrial fibrillation. These include cerebral infarction (both micro and macro embolic events), cerebral microbleeds including those secondary to therapeutic anticoagulation, an increased inflammatory state, cerebral hypoperfusion, and a genetic predisposition to both diseases. Treatments designed to target each of these mechanisms have led to mixed results and there are no specific interventions that have definitively led to a reduction in the incidence of cognitive dysfunction.

Summary
The relationship between cognitive dysfunction and atrial fibrillation remains poorly understood. Standard of care currently focuses on reducing risk factors, managing stroke risk, and maintaining sinus rhythm in appropriately selected patients. Further work needs to be conducted in this area to limit the progression of cognitive dysfunction in patients with atrial fibrillation.
Randomized, double-blind, controlled trial of a combination of alpha-lipoic acid and pregabalin for neuropathic pain: the PAIN-CARE trial
Authors: Gilron Ian , Robb Sylvia , Tu Dongsheng , Holden Ronald R. , Jackson Alan C. , Duggan Scott , Milev Roumen 
Published: September 2023

Abstract
We compared a combination of the nonsedating antioxidant, alpha-lipoic acid (ALA), with the sedating anticonvulsant, pregabalin, vs each monotherapy to treat neuropathic pain due to peripheral neuropathies. In this randomized, double-blind, 3-period crossover trial, participants received oral ALA, pregabalin, and their combination—each for 6 weeks. The primary outcome was mean daily pain intensity at maximal tolerated doses (MTD); secondary outcomes included quality of life (SF-36), sleep (Medical Outcomes Study-Sleep Scale), adverse effects, drug doses, and other measures. Of 55 participants randomized (20—diabetic neuropathy, 19—small fiber neuropathy, and 16—other neuropathies), 46 completed 2 periods, and 44 completed 3. At MTD, the primary outcome of mean pain intensity (0-10) was 5.32 (standard error, SE = 0.18), 3.96 (0.25), 3.25 (0.25), and 3.16 (0.25) at baseline, ALA, pregabalin, and combination, respectively (P < 0.01 for ALA vs combination and pregabalin). Treatment differences were similar in subgroups with diabetic neuropathy and with other neuropathies. SF-36 total scores (higher number indicates better quality of life) were 66.6 (1.88), 70.1 (1.88), and 69.4 (1.87) with ALA, pregabalin, and combination (P < 0.05 for ALA vs combination and pregabalin). At MTD, there were no statistically significant treatment differences in adverse effects or drug doses. This trial demonstrates superiority of pregabalin vs ALA but provides no evidence to suggest added benefit of combining ALA with pregabalin to treat neuropathic pain.
HPV+ head and neck cancer–derived small extracellular vesicles communicate with TRPV1+ neurons to mediate cancer pain
Authors: Inyang Kufreobong E. , Evans Christine M. , Heussner Matthew , Petroff Margaret , Reimers Mark , Vermeer Paola D. , Tykocki Nathan , Folger Joseph K. , Laumet Geoffroy 
Published: September 2023

Abstract
Severe pain is often experienced by patients with head and neck cancer and is associated with a poor prognosis. Despite its frequency and severity, current treatments fail to adequately control cancer-associated pain because of our lack of mechanistic understanding. Although recent works have shed some light of the biology underlying pain in HPV-negative oral cancers, the mechanisms mediating pain in HPV+ cancers remain unknown. Cancer-derived small extracellular vesicles (cancer-sEVs) are well positioned to function as mediators of communication between cancer cells and neurons. Inhibition of cancer-sEV release attenuated pain in tumor-bearing mice. Injection of purified cancer-sEVs is sufficient to induce pain hypersensitivity in naive mice that is prevented by QX-314 treatment and in Trpv1

−/−
mice. Cancer-sEVs triggered calcium influx in nociceptors, and inhibition or ablation of nociceptors protects against cancer pain. Interrogation of published sequencing data of human sensory neurons exposed to human cancer-sEVs suggested a stimulation of protein translation in neurons. Induction of translation by cancer-sEVs was validated in our mouse model, and its inhibition alleviated cancer pain in mice. In summary, our work reveals that HPV+ head and neck squamous cell carcinoma–derived sEVs alter TRPV1+ neurons by promoting nascent translation to mediate cancer pain and identified several promising therapeutic targets to interfere with this pathway.
Physician Assistant Student Attitudes Toward Gamification of Cardiac Auscultation Instruction
Authors: Garvick Sarah , Gillette Chris , Bates Nathan , Jackson Toni , Gao Hong , Crandall Sonia 
Published: September 2023

Introduction
Current physician assistant (PA) learners have a clear preference for interactive learning that is vibrantly present in new media technologies. At present, there is a paucity of research regarding use or acceptability of gamification in PA education. The purpose of this study was to examine PA students' experience with, attitudes toward, and outcomes of a gamified cardiac auscultation curriculum.

Methods
Faculty at one institution designed an interactive Mobile App Cardiac Auscultation Curriculum (MACAC). The MACAC incorporates independent and group learning using the Littmann Learning mobile app. Author-created surveys as well as knowledge and auscultation assessment tools were delivered to all students.

Results
Most of the students recommended the use of the app for future cohorts and reported confidence to accurately identify normal and abnormal heart sounds. Knowledge and auscultation assessment scores demonstrated proficiency in identification of normal and abnormal heart sounds.

Discussion
Gamification research is important because blended learning that incorporates new media technologies with traditional approaches can help overcome the limitations of passive learning environments. This study provides evidence that the use of a mobile app can be an effective and innovative method to teach cardiac auscultation to the 21st century PA learners.
Breast cancer pre-clinical screening using infrared thermography and artificial intelligence: a prospective, multicentre, diagnostic accuracy cohort study
Authors: Wang Xuefei , Chou Kuanyu , Zhang Guochao , Zuo Zhichao , Zhang Ting , Zhou Yidong , Mao Feng , Lin Yan , Shen Songjie , Zhang Xiaohui , Wang Xuejing , Zhong Ying , Qin Xue , Guo Hailin , Wang Xiaojie , Xiao Yao , Yi Qianchuan , Yan Cunli , Liu Jian , Li Dongdong , Liu Wei , Liu Mengwen , Ma Xiaoying , Tao Jiangtao , Sun Qiang , Zhai Jidong , Huang Likun 
Published: September 2023

Background:
Given the limited access to breast cancer (BC) screening, the authors developed and validated a mobile phone-artificial intelligence-based infrared thermography (AI-IRT) system for BC screening.

Materials and methods:
This large prospective clinical trial assessed the diagnostic performance of the AI-IRT system. The authors constructed two datasets and two models, performed internal and external validation, and compared the diagnostic accuracy of the AI models and clinicians. Dataset A included 2100 patients recruited from 19 medical centres in nine regions of China. Dataset B was used for independent external validation and included 102 patients recruited from Langfang People’s Hospital.

Results:
The area under the receiver operating characteristic curve of the binary model for identifying low-risk and intermediate/high-risk patients was 0.9487 (95% CI: 0.9231–0.9744) internally and 0.9120 (95% CI: 0.8460–0.9790) externally. The accuracy of the binary model was higher than that of human readers (0.8627 vs. 0.8088, respectively). In addition, the binary model was better than the multinomial model and used different diagnostic thresholds based on BC risk to achieve specific goals.

Conclusions:
The accuracy of AI-IRT was high across populations with different demographic characteristics and less reliant on manual interpretations, demonstrating that this model can improve pre-clinical screening and increase screening rates.
Cost-effectiveness and prognostic model of hepatic arterial infusion chemotherapy for hepatocellular carcinoma with high tumor burden and/or Vp4 tumor thrombus compared with sorafenib: a post-hoc analysis of the FOHAIC-1 trial
Authors: Chen Qi-Feng , Lyu Ning , Wang Xun , Jiang Xiong-Ying , Hu Yue , Chen Song , Zhong Sui-Xing , Huang Zi-Lin , Chen Minshan , Zhao Ming 
Published: September 2023

Objectives:
The phase III FOHAIC-1 trial revealed that hepatic arterial infusion of chemotherapy (HAIC) improved overall survival compared to sorafenib in the high-risk hepatocellular carcinoma (HCC). This study therefore set out to evaluate the cost-effectiveness and establish a prognostic clinico-radiological score of HAIC.

Materials and methods:
A total of 409 patients with high-risk HCC who received HAIC between 2014 and 2020 were included. A Markov model was applied in the cost-effectiveness analysis using data from the FOHAIC-1 trial. In prognosis analysis, a clinico-radiological score was developed using a Cox-regression model and subsequently confirmed in the internal validation and test cohorts. The area under the curve from receiver operator characteristic analysis was used to assess the performance of the clinico-radiological score.

Results:
HAIC resulted in an incremental cost-effectiveness ratio of $10190.41/quality-adjusted life years compared to sorafenib, which was lower than the willingness-to-pay threshold. Probabilistic sensitivity analysis predicted a ≥99.9% probability that the incremental cost-effectiveness ratio was below the willingness-to-pay. The Cox analysis identified five factors, namely extrahepatic metastasis (m), arterial enhancing type (a), tumor number (nu), albumin-bilirubin index (a), and involved lobe (l), which together comprise the clinico-radiological score (HAIC-manual). Patients were classified into three groups based on the number of factors present, with cutoffs at 2 and 4 factors. The stratified median overall survival for these groups were 21.6, 10.0, and 5.9 months, respectively (P<0.001). These findings were verified through internal validation and test cohorts with a significance level of P≤0.01. The time-dependent area under the curve from receiver operator characteristic for the ability of the HAIC-manual to predict survival in 1, 2, and 3 years were 0.71, 0.76, and 0.78, which significantly outperformed existing staging systems.

Conclusion:
HAIC is a promising and cost-effective strategy for patients with high-risk HCC. The clinico-radiological score may be a simple prognostic tool for predicting HAIC treatment.
Do Sport-Related Concussions Later in the Season Take Longer to Recover From?
Authors: Jo Jacob , Hill Tyler M. , Williams Kristen L. , Prosak Olivia L. , Amedy Amad , Anesi Trevor J. , Terry Douglas P. , Zuckerman Scott L. 
Published: September 2023

Objective:
In a cohort of high-school football athletes with sport-related concussion (SRC), we sought to investigate the role of seasonality, defined as time of injury during a season, on recovery.

Design:
Retrospective cohort study.

Setting:
Regional sport concussion center.

Participants:
High-school football athletes ages 14 to 19 –years old who sustained an SRC from 11, 2017 to 04, 2022.

Intervention:
Athletes were divided into 3 groups based on seasonality: early, middle, and late season.

Main Outcome Measures:
The primary outcomes were initial Post-Concussion Symptom Scale score and recovery, as defined by time to return-to-learn (RTL), symptom resolution, and return-to-play (RTP). Descriptive statistics, analysis-of-variance, t tests, and multivariable regressions were performed.

Results:
Of our cohort of 273 high-school football players who sustained an SRC, 97 (35.5%) sustained an SRC during early season, 107 (39.2%) during middle season, and 69 (25.3%) during late season. Compared with late-season concussions, early-season concussions took less days to symptom resolution (early = 11.5 ± 12.9 vs late = 25.5 ± 27.0, P = 0.03), but no differences were found in days to RTL (early = 5.3 ± 4.8 vs late = 7.2 ± 15.8, P = 0.51) and RTP (early = 13.5 ± 11.8 vs late = 23.0 ± 22.8, P = 0.08). Seasonality was not a significant predictor for any recovery metric in multivariable regressions.

Conclusion:
Sport-related concussions occurring in the early third of the season took significantly less time to symptom resolution than those occurring in the later third of the season; however, this was not statistically significant in multivariable analyses. No association was observed between seasonality and time to RTL and RTP. A trend of worse recovery with concussions later in the season may be present.
Clinically Significant Prostate Cancer in Men With High-Grade Intraepithelial Prostatic Intraepithelial Neoplasia or Atypical Small Acinar Proliferation
Authors: Norman Robert D. , Garg Harshit , Rickborn Lanette , Kaushik Dharam , Pruthi Deepak Kumar , Mansour Ahmed M. , Thompson Ian M. , Liss Michael A. 
Published: September 2023

Purpose:
The clinical management of Atypical Small Acinar Proliferation (ASAP) and High-Grade Prostate Intraepithelial Neoplasia (HGPIN) varies significantly. The aim of this study was to characterize the incidence and natural history of ASAP and HGPIN lesions to optimize follow-up strategies.

Materials and Methods:
A retrospective analysis of patients at a VA Medical Center who underwent a prostate needle biopsy between 1988 and 2017 was performed. The pathological lesions were grouped as ASAP, HGPIN, and ASAP & HGPIN. The primary outcome was the incidence of clinically significant prostate cancer (csPCa) defined as grade group ≥2 prostate cancer.

Results:
Of 6104 patients screened, 312 patients included having ASAP (n = 70, 1.1%), HGPIN (n = 222, 3.6%), or ASAP & HGPIN (n = 20, 0.3%). Follow-up biopsy was performed in 99.3% of patients. The incidence of prostate cancer in ASAP, HGPIN, or ASAP & HGPIN groups was 46.3%, 37%, and 68.4%, respectively (P = .03). However, the rate of csPCa was similar across the 3 groups (10.1% in ASAP, 10.3% in HGPIN, and 10.5% in ASAP & HGPIN, P = .6). The median time to cancer diagnosis was significantly shorter for patients with ASAP (2.8 years for ASAP, 4.9 years for HGPIN, and 1.5 years for ASAP & HGPIN, P = .001); however, there was no significant difference in time to diagnosis of csPCa between the various groups (P = .7).

Conclusion:
Both ASAP and HGPIN have a low risk of progression to csPCa. This, coupled with a prolonged time to any cancer diagnosis, suggests that immediate repeat biopsy might not be necessary among these patients.
Identification and detection of microRNA kidney disease biomarkers in liquid biopsies
Authors: Smith Daniel A. , Redman James E. , Fraser Donald J. , Bowen Timothy 
Published: September 2023

Purpose of review
MicroRNAs (miRNAs) are emerging rapidly as a novel class of biomarkers of major organ disorders, including kidney diseases. However, current PCR-based detection methods are not amenable to development for high-throughput, cost-effective miRNA biomarker quantification.

Recent findings
MiRNA biomarkers show significant promise for diagnosis and prognosis of kidney diseases, including diabetic kidney disease, acute kidney injury, IgA nephropathy and delayed graft function following kidney transplantation. A variety of novel methods to detect miRNAs in liquid biopsies including urine, plasma and serum are being developed. As miRNAs are functional transcripts that regulate the expression of many protein coding genes, differences in miRNA profiles in disease also offer clues to underlying disease mechanisms.

Summary
Recent findings highlight the potential of miRNAs as biomarkers to detect and predict progression of kidney diseases. Developing in parallel, novel methods for miRNA detection will facilitate the integration of these biomarkers into rapid routine clinical testing and existing care pathways. Validated kidney disease biomarkers also hold promise to identify novel therapeutic tools and targets.

Video abstract

http://links.lww.com/CONH/A43
Update on the evaluation and management of dysphagia in sporadic inclusion body myositis
Authors: Garand Kendrea L. (Focht) , Malandraki Georgia A. , Dimachkie Mazen M. 
Published: September 2023

Purpose of review
Dysphagia is a common symptom of sporadic inclusion body myositis (IBM), affecting disease trajectory and patient quality-of-life. Despite this, it is considerably understudied. The purpose of this review is to summarize current evidence related to the evaluation and management of dysphagia in IBM. We highlight a patient case involving a multidisciplinary management approach, and we encourage continued exploration of exercises for delaying progression and improving impairments in patients with IBM and dysphagia.

Recent findings
Recent investigations confirm that dysphagia in IBM is a debilitating and complex symptom that warrants timely evaluation and management. Further, they highlight the lack of validation of standardized swallowing-related metrics specifically for IBM and the limited evidence supporting a consensus of management approaches. Small scale research and clinical anecdotal data support a multidisciplinary and multipronged patient-centered approach, including rehabilitative exercise protocols, for dysphagia management in IBM.

Summary
A paucity exists in the literature to effectively guide clinical decision-making for patients with IBM and dysphagia. Given this, it is our belief that a careful multidisciplinary and multipronged patient-centered approach is critical for dysphagia management in IBM. Prospective, longitudinal research on the underlying mechanisms of swallowing dysfunction using advanced and validated swallowing-related outcome measures is urgently needed.
Development of a Metaverse Online Learning System for Undergraduate Nursing Students
Authors: Ryu Hyeongju , Lee Hyeongsuk , Yoo Hye Jin 
Published: September 2023

Background:
An active online learning environment enables 2-way communication wherein students can engage in problem-based learning and projects, unlike fragmented lecture-style classes.

Purpose:
This pilot study aimed to develop a metaverse-based online learning system and evaluate its usability.

Methods:
A rapid prototyping model and Gather.town was used to design and develop a metaverse classroom. Participants were 10 nursing students from a college in South Korea. To evaluate usability, 10 tasks were configured and 2 pilot tests were conducted. The degree of difficulty, time required to perform tasks, and students' experience were investigated.

Results:
The Metaverse for Education of Nursing Students was successfully completed, incorporating student feedback and addressing identified areas for improvement.

Conclusion:
This study reflects a learner-centered educational environment through the direct participation in the development process of the instructors who conducted the lectures. The metaverse space can be widely applied in creative nursing education in the future.
Case Report: Spontaneous Closure of Idiopathic Full-thickness Macular Hole and Early Development of Lamellar Hole
Authors: Tozzi Luigi , Gius Irene , Greggio Angelo , Meduri Alessandro , De Salvo Gabriella , Parolini Barbara , Frisina Rino 
Published: September 2023

SIGNIFICANCE
Spontaneous closure of an idiopathic full-thickness macular hole (FTMH) is a rare event. The underlying mechanisms are unclear because of the difficulty in detecting subtle structural changes even with serial imaging. Previous reports are largely optical coherence tomography (OCT) based, but multimodal imaging could highlight new information.

PURPOSE
This study aimed to report the spontaneous closure of an idiopathic FTMH (iFTMH) and its recurrence and late closure documented by serial OCT integrated with multimodal imaging modalities and microperimetry (MP).

CASE REPORT
A healthy 46-year-old man was referred to the Department of Ophthalmology of the University of Padova for an iFTMH in the right eye with preserved visual acuity. The patient was scheduled for monthly controls up to 12 months by an integrated assessment of OCT, angiography-OCT, short-wavelength fundus autofluorescence, and MP. Two months later, tracked OCT scans showed a closure of the hole with a residual lamellar macular hole. Sequential examinations revealed a discontinuation of photoreceptors (ellipsoid zone) and a recurrence of iFTMH, and 7 months later, iFTMH reclosed without any relevant changes up to 12 months. Foveal avascular zone area increased from the baseline reaching its maximum value when iFTMH recurred. Two hyper–fundus autofluorescence points were detected in the foveal area, one progressively decreased and one reached the most intense signal when iFTMH recurred. Retinal sensitivity decreased mostly in one hyper–fundus autofluorescence point when the ellipsoid zone line discontinued and reached the lowest value when iFTMH recurred, and increased mostly in the other points when iFTMH reclosed.

CONCLUSIONS
Spontaneous iFTMH closure, as well as its recurrence and reclosure, is a rare event. By monitoring with multiple imaging modalities, MP and their overlaying elaboration can add new biomarkers with diagnostic and prognostic value.