Luminance and thresholding limitations of virtual reality headsets for visual field testing

by Changseok Lee, Liam Redden, Vivian Eng, Brennan Eadie

Purpose

To investigate the luminance capacity and achievable threshold levels of commercially employed virtual reality (VR) devices for visual field testing.

Methods

This two-part study included (1) a literature review of VR headsets used for perimetry with luminance data extracted from technical specifications in publications and manufacturers; and (2) empirical evaluation of three most employed VR headsets in the literature using a custom virtual testing environment.

Results

Three most employed VR devices for visual field testing were Pico Neo, Oculus Quest, and HTC Vive. The maximum reported luminance was 250 cd/m² for the HTC Vive Pro. Information on luminance measurement was not consistently available, reporting only handheld luminance meters. Empirical measurements show that handheld luminance meters significantly overestimate luminance compared to standard spectroradiometers. Measured luminance varies significantly across aperture size and decreases for peripheral stimuli up to 30 degrees peripherally. Assuming conventional background of 10 cd/m², the best performance with lowest possible thresholding was with HTC Vive at 16dB, corresponding to luminance of 80 cd/m² centrally. Oculus Quest 2 and Pico Neo 3 had minimum threshold of 20dB.

Conclusion

Commercially available VR devices do not meet luminance requirements or threshold sensitivities for visual field testing. Current VR technology is not designed—nor has the capacity—to threshold at mid-to-low dB ranges, which limits accuracy in diagnosing and monitoring defects seen in glaucoma. Translational Relevance: This study highlights the technical limitations of current commercially available VR devices for visual field testing and significant variables in evaluating luminance performance in these devices.

Construct prediction models for low muscle mass with metabolic syndrome using machine learning

by Yanxuan Wu, Fu Li, Hao Chen, Liang Shi, Meng Yin, Fan Hu, Gongchang Yu

Background

Metabolic syndrome (MetS) and sarcopenia are major global public health problems, and their coexistence significantly increases the risk of death. In recent years, this trend has become increasingly prominent in younger populations, posing a major public health challenge. Numerous studies have regarded reduced muscle mass as a reliable indicator for identifying pre-sarcopenia. Nevertheless, there are currently no well-developed methods for identifying low muscle mass in individuals with MetS.

Methods

A total of 2,467 MetS patients (aged 18–59 years) with low muscle mass assessed by dual-energy X-ray absorptiometry (DXA) were included using data from the 2011–2018 National Health and Nutrition Examination Survey (NHANES). Least Absolute Shrinkage and Selection Operator (LASSO) regression was then used to screen for important features. A total of nine Machine learning (ML) models were constructed in this study. Area under the curve (AUC), F1 Score, Recall, Precision, Accuracy, Specificity, PPV, and NPV were used to evaluate the model’s performance and explain important predictors using the Shapley Additive Explain (SHAP) values.

Results

The Logistic Regression (LR) model performed the best overall, with an AUC of 0.925 (95% CI: 0.9043, 0.9443), alongside strong F1-score (0.87) and specificity (0.89). Five important predictors are displayed in the summary plot of SHAP values: height, gender, waist circumference, thigh length, and alkaline phosphatase (ALP).

Conclusion

This study developed an interpretable ML model based on SHAP methodology to identify risk factors for low muscle mass in a young population of MetS patients. Additionally, a web-based tool was implemented to facilitate sarcopenia screening.

Advancing fall risk prediction in older adults with cognitive frailty: A machine learning approach using 2-year clinical data

by Catherine Park, Namhee Kim, Miji Kim, Chang Won Won, Beom-Chan Lee

Falls are a critical concern in older adults with cognitive frailty (CF). However, previous studies have not fully examined whether machine learning models can predict falls in older individuals with CF. The 2-year longitudinal data set from the Korean Frailty and Aging Cohort Study and machine learning approach were utilized to predict fall risk. We analyzed multidimensional health data, including demographics, clinical conditions, as well as the physical and psychological health factors of 443 older adults with CF identified out of 2,404 older adults. For fall risk prediction, we developed a machine learning framework incorporating logistic regression, bootstrapping, and recursive feature elimination. Statistical analysis revealed significant differences between the non-faller and faller groups for nine clinical conditions as well as physical and psychological variables. Using nine significant variables, our machine-learning-based model demonstrated good predictive performance with an area under the curve (AUC) exceeding 80%. Furthermore, our machine learning framework identified four optimal variables: the number of Fried physical frailty (PF) phenotypes, PF-Mobility scores, scores from the Korean version of the Short Geriatric Depression Scale, and scores from SARC-F (consisting of five components: strength, assistance with walking, rising from a chair, climbing stairs, and experiencing falls). It demonstrated excellent predictive performance, with an AUC, sensitivity, specificity, and accuracy exceeding 95%. These variables reflect the critical association between physical and psychological health and fall risk. These findings underscore the importance of integrating multidimensional health data with machine learning methodologies to accurately predict fall risk in older adults with CF, design targeted interventions, and enable healthcare professionals to implement strategies to reduce and prevent such falls.

Proximal and distal middle cerebral artery diameter ratio and lenticulostriate artery infarction

by Jun Sang Yoo, Jae Hyun Choi, Jae Young Park, Jeong Yun Song, Jun Young Chang, Dong-Wha Kang, Sun U. Kwon, Hang Jin Jo, Bum Joon Kim

Background

Lipohyalinotic degeneration (LD) and branch atheromatous disease (BAD) can contribute to subcortical infarctions in the lenticulostriate artery (LSA) territory. This study aimed to identify the association between the proximal and distal middle cerebral artery (MCA) diameter ratio and the two different pathomechanisms of LSA infarction.

Methods

Patients with acute LSA infarctions categorized as small vessel occlusive disease were included. Demographic and clinical data, along with MCA geometrical variables, were collected. LD and BAD were differentiated based on the length of the infarction diameter and number of axial slices. The proximal/distal M1 diameter ratio was calculated. MCA geometrics between LD and BAD were compared. Independent factors associated with LD were investigated. Computational fluid dynamics (CFD) analysis was used to evaluate hemodynamic parameters.

Results

A total of 117 patients were included, of whom 64 (54.7%) and 53 (45.3%) were classified as BAD and LD, respectively. LD was associated with hypertension and favorable prognosis. MCA geometric variables revealed that LD had a higher proximal/distal M1 diameter ratio, indicating a potential distinguishing factor. Multivariate analysis confirmed the independent association between LD and the proximal/distal M1 diameter ratio. The proximal/distal M1 diameter ratio also showed a positive correlation with the number of ipsilesional lacunes. CFD analysis showed that the LD model had faster, greater blood influx into LSAs and higher wall shear stress and pressure gradient compared with the BAD model.

Conclusions

This study suggests MCA geometry, particularly the proximal/distal M1 diameter ratio, may serve as an independent factor for identifying LD.

Targeting tumor-associated genes, immune response, and circulating tumor cells in intrahepatic cholangiocarcinoma: Therapeutic potential of <i>Atractylodes lancea</i> (Thunb.) DC

by Pongsakorn Martviset, Pathanin Chantree, Nisit Tongsiri, Tullayakorn Plengsuriyakarn, Kesara Na-Bangchang

Cholangiocarcinoma (CCA) is one of the most aggressive cancers with a poor prognosis. Current treatment strategies involve hepatobiliary surgery, chemotherapy, radiotherapy, and supportive care; however, the success of these treatments remains limited. Therefore, this study investigated the potential of Atractylodes lancea (Thunb) D.C. (AL) in limiting the progress of CCA by targeting the expression of cancer-related genes involved in immune responses and circulating tumor cells. The study was part of Phase 2A clinical trial in advanced-stage intrahepatic iCCA (iCCA) patients: Group 1 (n = 16) received low-dose AL (capsule formulation of the standardized extract of AL: CMC-AL) with standard supportive care, Group 2 (n = 16) received high-dose AL with standard supportive care, and Group 3 (n = 16) received standard supportive care alone. Venous whole blood samples (EDTA, 5 ml) were collected from each patient on Day 1 and Day 90 and the non-CCA subjects (n = 16) on Day 1. Fifty-nine samples (48 and 11 samples for Day 1 and Day 90, respectively) were processed for total RNA isolation. Gene expression was evaluated using reverse transcription followed by a PCR array. Regardless of dosage, gene expression patterns in the AL-treated groups closely resembled those of the healthy subjects. Specifically, cancer-associated genes, including VEGF-A, NR4A3, Ki-67, and EpCAM, were significantly down-regulated. Additionally, the expression levels of immune-related genes were modulated in AL-treated patients. The treatment groups exhibited lower levels of the pro-inflammatory cytokine IL-6, increased expression of the anti-inflammatory cytokine IL-10, and cell-mediated immune-related molecules such as CTLA4 and PFR1. These findings suggest the potential of AL for iCCA treatment. However, additional studies are required to confirm the correlation between gene and protein expression profiles, as well as CTCs profile.

Effect of perioperative lidocaine infusion on the subjective quality of recovery after surgery: Protocol for an updated systematic review and meta-analysis

by Qianli Huang, Changhui Shao, Wei Wei, Shan Ou

Background

Lidocaine is increasingly used for surgical patients requiring general anesthesia. However, its clinical benefits on postoperative recovery quality are not well established. Our main objective aims to summarize the evidence regarding the effectiveness of perioperative lidocaine infusion on postoperative subjective quality of recovery (QoR).

Methods and analysis

This protocol will be conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) guideline. This systematic review will include randomized controlled trials (RCTs) from their inception until December 31st, 2024 with no language restrictions. The major databases including PubMed, Embase, and the Cochrane library will be comprehensively searched and supplemented by a hand searching reference lists of all included articles. Searches will involve studies assessing the efficacy of the perioperative lidocaine infusion for improving postoperative QoR, in comparison to placebo, or on treatment. The two authors will independently screen studies, extract study data and assess bias risk of the studies. The subjective QoR (QoR-15, QoR-40) on postoperative day 1–3 will be defined as primary outcome, whereas secondary outcomes will include morphine consumption, incidence of postoperative nausea and vomiting, time to first bowel movement, time to first flatus, and length of hospital stay. A meta-analysis will be performed using Review Manager 5.3 software. Sensitivity analyses, subgroup analysis and publication bias will also be conducted. The evidence quality of pooled results will be assessed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.

Discussion

This review and meta-analysis is anticipated to provide the evidence for the role of intravenous lidocaine on the subjective quality of recovery after surgery. In addition, the findings from this review will help clinicians with developing effective and safe perioperative anesthetic management regimens for surgery patients.

Study registration

PROSPERO registration number: CRD42024585866

Mis-splicing drives loss of function of p53^E224D point mutation

by Ian C. Lock, Nathan H. Leisenring, Warren Floyd, Eric S. Xu, Lixia Luo, Yan Ma, Erin C. Mansell, Diana M. Cardona, Chang-Lung Lee, David G. Kirsch

Background

The tumor suppressor p53 (Trp53), also known as p53, is the most commonly mutated gene in cancer. Canonical p53 DNA damage response pathways are well characterized and classically thought to underlie the tumor suppressive effect of p53. Challenging this dogma, mouse models have revealed that p53-driven apoptosis and cell cycle arrest are dispensable for tumor suppression. Here, we investigated the inverse context of a p53 mutation predicted to drive the expression of canonical targets but is detected in human cancer.

Methods

We established a novel mouse model with a single base pair mutation (GAG>GAT, p53^E221D) in the DNA-Binding domain that has wild-type function in screening assays, but is paradoxically found in human cancer in Li-Fraumeni syndrome. Using mouse p53^E221D and the analogous human p53^E224D mutants, we evaluated expression, transcriptional activation, and tumor suppression in vitro and in vivo.

Results

Expression of human p53^E224D from cDNA translated to a fully functional p53 protein. However, p53^E221D/E221D RNA transcribed from the endogenous locus is mis-spliced resulting in nonsense-mediated decay. Moreover, fibroblasts derived from p53^E221D/E221D mice do not express a detectable protein product. Mice homozygous for p53^E221D exhibited increased tumor penetrance and decreased life expectancy compared to p53^WT/WT animals.

Conclusions

Mouse p53^E221D and human p53^E224D mutations lead to splice variation and a biologically relevant p53 loss of function in vitro and in vivo.

Evidence that flocking behavior is rewarded by singing, flock mates, and mu opioid receptors in the nucleus accumbens

by Alyse N. Maksimoski, Taviah A. Levenson, Changjiu Zhao, Lauren V. Riters

It has been proposed that social groups are maintained both by reward resulting from positive social interactions and by the reduction of a negative state that would otherwise be caused by social separation. European starlings, Sturnus vulgaris, develop strong conditioned place preferences for places associated with the production of song in flocks outside the breeding season (gregarious song) and singers are motivated to rejoin the flock following removal. This indicates that the act of singing in flocks is associated with a positive affective state and raises the possibility that reward induced by song in flocks may play a role in flock maintenance. The goal of this study was to begin to test this hypothesis. We found that birds that sang full songs developed stronger conditioned place preferences than non-singing birds for places associated with flock mates, indicating that singers find the presence of flock mates to be rewarding. Regardless of song rate, the presence of flock mates also induced analgesia (a reflection of the reduction of a negative state). This form of analgesia has been shown to be an indirect measure of opioid release, suggesting that the presence of flock mates may induce opioid-mediated reward. Consistent with this possibility, the numbers of mu opioid receptor immunolabeled cells in the nucleus accumbens correlated positively with measurements of gregarious song and other social behaviors. Results suggest that both gregarious song and social contact promote flock cohesion and that opioids released onto mu opioid receptors in the nucleus accumbens may play an important role.

Association between normal weight obesity and comorbidities and events of cardiovascular diseases among adults in South China

by Miaomiao Ma, Deliang Lv, Xiaobing Wu, Yuqing Chen, Shimiao Dai, Yutian Luo, Hui Yang, Wei Xie, Fengzhu Xie, Qinggang Shang, Ziyang Zhang, Zhiguang Zhao, Ji-Chang Zhou

Background

The increased risks for cardiovascular comorbidities and cardiovascular diseases (CVD) in populations with normal weight obesity (NWO) have not been well-identified. We aimed to study their associations in an adult population in South China.

Methods

Based on the CVD prevalence of 4% in Shenzhen and a calculated sample size of 6,000, a cross-sectional study with a multi-stage stratified cluster sampling method was conducted in Shenzhen City. The cardiovascular comorbidities being studied were abdominal obesity (AO), diabetes, hypertension, dyslipidemia, metabolic syndrome, and chronic kidney disease, while the CVD events were occurrences of myocardial infarction and strokes. Questionnaire surveys, physical examinations, and laboratory tests were performed. NWO was defined as a condition with the highest tertile of body fat percentage (BF%) among the normal body mass index (BMI) range (18.5–23.9 kg/m²). Continuous data were reported as mean [standard deviation (SD)] and categorical data as percentages (%). CVD comorbidities and CVD events and their detection rates in different groups were compared using ANONA analysis and Chi-squared test. Spearman’s correlation coefficients between BF% and cardiometabolic abnormalities were calculated by partial correlation analysis. Multivariate logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for BF%, CVD comorbidities, and CVD events, adjusted for multiple confounders.

Results

Among the total 6,240 subjects who completed the study and had BMI and BF% data available, 3,086 had normal BMI. The prevalence of NWO was 16.36%, with 13.15% for men and 19.54% for women. With confounders adjusted, the risks of AO (OR = 6.05, 95%CI = 3.40–10.75), essential hypertension (OR = 1.56, 95%CI = 1.09–2.22), dyslipidemia (OR = 1.85, 95%CI = 1.49–2.29), and metabolic syndrome (OR = 4.61, 95%CI = 2.32–9.18) were significantly increased in the populations with NWO compared with the population without NWO (P Conclusion

NWO was found to be positively associated with CVD comorbidities but not with CVD events. The current study provides a ground to conduct further studies on whether body fat affects the risk of occurrence of CVD events and the underlying mechanisms in the future.

Effectiveness of treatment for concussion-related convergence insufficiency: The CONCUSS study protocol for a randomized clinical trial

by Tara L. Alvarez, Mitchell Scheiman, Suril Gohel, Farzin Hajebrahimi, Melissa Noble, Ayushi Sangoi, Chang Yaramothu, Christina L. Master, Arlene Goodman

Purpose

To describe CONCUSS, a randomized clinical trial (RCT) designed to compare the following: the effectiveness of immediate office-based vergence/accommodative therapy with movement (OBVAM) to delayed OBVAM as treatments for concussion-related convergence insufficiency (CONC-CI) to understand the impact of time (watchful waiting), the effect of OBVAM dosage (12 versus 16 therapy sessions), and to investigate the underlying neuro-mechanisms of OBVAM on CONC-CI participants.

Methods

CONCUSS is an RCT indexed on https://clinicaltrials.gov/study/NCT05262361 enrolling 100 participants aged 11–25 years with medically diagnosed concussion, persistent post-concussive symptoms 4–24 weeks post-injury, and symptomatic convergence insufficiency. Participants will receive standard concussion care and will be randomized to either immediate OBVAM or delayed (by six weeks) OBVAM. At the Outcome 1 examination (week 7), clinical assessments of success as determined by changes in the near point of convergence (NPC), positive fusional vergence (PFV), and symptoms will be compared between the two treatment groups. After the Outcome 1 visit, those in the delayed group receive 16 visits of OBVAM, while those in the immediate OBVAM group receive four more therapy visits. Outcome 2 assessment will be used to compare both groups after participants receive 16 sessions of OBVAM. The primary measure is the between-group differences of the composite change in the NPC and PFV at the Outcome 1 visit. Secondary outcome measures include individual clinical measures, objective eye-tracking parameters, and functional brain imaging.

Conclusions

Major features of the study design include formal definitions of conditions and outcomes, standardized diagnostic and treatment protocols, a delayed treatment arm, masked outcome examinations, and the incorporation of objective eye movement recording and brain imaging as outcome measures. CONCUSS will establish best practices in the clinical care of CONC-CI. The objective eye movement and brain imaging, correlated with the clinical signs and symptoms, will determine the neuro-mechanisms of OBVAM on CONC-CI.

Arthroscopic assisted versus open core decompression for osteonecrosis of the femoral head: A systematic review and meta-analysis

by Wensi Ouyang, Guimei Guo, Jie Xia, Changwei Zhao, Xiaoling Zhou

Background

Minimally invasive treatment options for osteonecrosis of the femoral head (ONFH) have been a prominent area of research in recent years. Arthroscopic-assisted treatments have been applied in the clinical management of ONFH; however, high-quality evidence verifying their effectiveness and safety is still lacking.

Objective

To systematically assess the clinical efficacy and safety of arthroscopic-assisted core decompression (AACD) in treating ONFH.

Methods

A comprehensive literature search was conducted in PubMed, Web of Science, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure, China Science and Technology Journal Database, WanFang, and the Chinese BioMedical Literature Database, from inception to June 25, 2024. We identified randomized controlled trials and non-randomized controlled studies on AACD for the treatment of ONFH based on predefined inclusion and exclusion criteria. A meta-analysis was performed using Review Manager 5.4.1 and Stata 17.0 software. The analyzed outcomes included operative time, intraoperative blood loss, length of hospital stay, postoperative femoral head collapse rate, Harris hip score, and postoperative complication rate. The Grades of Recommendations, Assessment, Development, and Evaluations (GRADE) system was used to assess the quality of evidence for the outcome indicators.

Results

A total of fourteen studies were included in this meta-analysis, comprising 1,063 patients-541 in the core decompression (CD) group and 522 in the AACD group. The meta-analysis revealed no significant differences between the two groups in terms of intraoperative blood loss, length of hospital stay, 12-month postoperative Harris hip score, or overall postoperative complication rate (P > 0.05). However, the AACD group had a longer operative time (MD = 31.19, 95% Cl: 5.32 to 57.07, P = 0.02) and a lower overall postoperative femoral head collapse rate (RR = 0.49, 95% Cl: 0.27 to 0.89, P = 0.02) compared with the CD group. Additionally, the AACD group showed significant improvements in Harris hip scores at 3 months (MD = 6.39, 95% Cl: 5.44 to 7.33, P P P P Conclusion

This meta-analysis suggests that AACD is an effective and safe treatment for patients with ONFH. However, due to the limited quantity and quality of the included studies, these results should be interpreted with caution. Further high-quality studies are recommended to confirm these findings.

Emergence of crucial evidence catalyzing the origin tracing of SARS-CoV-2

by Shunmei Chen, Cihan Ruan, Yutong Guo, Jia Chang, Haohao Yan, Liang Chen, Yongzhong Duan, Guangyou Duan, Jinlong Bei, Xin Li, Shan Gao

Since the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), its genetic and geographical origins remain unclear, resulting in suspicions about its natural origin. In one of our previous studies, we reported the presence of a furin cleavage site RRAR in the junction region between S1 and S2 subunits of the spike protein, which was discovered as the first crucial clue for the origin tracing of SARS-CoV-2. In the present study, we conducted an integrative analysis of new genome data from bat Sarbecovirus strains reported after the COVID-19 outbreak. The primary results included the identification of BANAL-20-52, Rp22DB159, and S18CXBatR24 as three close relatives of SARS-CoV-2 and the successful detection of seven out of nine key genomic features (designated as RC0-7 and ORF8) observed in wild types of SARS-CoV-2 in the three close relatives from Laos, Vietnam, and Yunnan province of China, respectively. The most significant contribution of the present study lies in the detection of RC1 in wild genotype in a bat Sarbecovirus population BANAL-20-52 belonging to. Encoding a segment of the NSP3 protein, RC1 was discovered as the second crucial clue for the origin tracing of SARS-CoV-2. Although RC0, encoding the junction furin cleavage site, remains undetected outside of the SARS-CoV-2 genome, Feuang of Laos is the sole place where eight of the nine wild-type features (RC1-7 and ORF8) have been detected.

Exploring novel immunotherapy biomarker candidates induced by cancer deformation

by Se Min Kim, Namu Park, Hye Bin Park, JuKyung Lee, Changho Chun, Kyung Hoon Kim, Jong Seob Choi, Hyung Jin Kim, Sekyu Choi, Jung Hyun Lee

Triple-negative breast cancer (TNBC) demands urgent attention for the development of effective treatment strategies due to its aggressiveness and limited therapeutic options [1]. This research is primarily focused on identifying new biomarkers vital for immunotherapy, with the aim of developing tailored treatments specifically for TNBC, such as those targeting the PD-1/PD-L1 pathway. To achieve this, the study places a strong emphasis on investigating Ig genes, a characteristic of immune checkpoint inhibitors, particularly genes expressing Ig-like domains with altered expression levels induced by "cancer deformation," a condition associated with cancer malignancy. Human cells can express approximately 800 Ig family genes, yet only a few Ig genes, including PD-1 and PD-L1, have been developed into immunotherapy drugs thus far. Therefore, we investigated the Ig genes that were either upregulated or downregulated by the artificial metastatic environment in TNBC cell line. As a result, we confirmed the upregulation of approximately 13 Ig genes and validated them using qPCR. In summary, our study proposes an approach for identifying new biomarkers applicable to future immunotherapies aimed at addressing challenging cases of TNBC where conventional treatments fall short.