Exact Test P-value Research Articles

A new frontier in biostatistics: evaluating the accuracy of ChatGPT-4 vs. R in analysing liver resection data

Background The rise of ChatGPT-4’s Data Analyst tool presents a new frontier for biostatistical computations. This study evaluates the reliability and improvements of ChatGPT-4 Data Analyst tool by comparing it to R package in performing biostatistical analysis on liver surgery patients. Methods Utilizing data from LiverGroup.org, we conducted our comparative study between October 2023 and March 2024. The variables analyzed by the R package and ChatGPT-4 Data Analyst included age, sex, hospital stay duration, income group, and mortality. Analysis on ChatGPT-4 were performed using two methods: a holistic prompt which included all-at-once analysis were requested and segmented prompts, one-by-one test request for analysis. After the analysis figures were requested from ChatGPT-4, comparison with R package figures was done. Results Descriptive analysis including N (%), Standard Deviation, and (25th–75th Percentile) were consistent between ChatGPT-4 March version and R with a minor variation in the holistic approach on the analysis performed in October. The inferential statistical results of ChatGPT-4 showed inconsistencies in October 2023 while March 2024 revealed accurate results with Crosstabulations, Kruskal Wallis, Wilcoxon Rank Sum, T-test, Pearson’s Chi-squared, and Fisher’s Exact test p-value. ChatGPT-4 March 2024 version was able to inform the user with possible inaccuracies in certain tests (Mann-Whitney U Test: Hospital stay vs mortality p value, Levene’s Test p-value: Age vs mortality, and Fisher’s Exact Test: Odds ratio gender vs. mortality 95% CI). The survival curve and box-and-whisker plot generated by ChatGPT-4 in March 2024 matched those generated by R package except for the CI of survival curve. Conclusions The high accuracy of ChatGPT-4 in certain biostatistical analysis has reached the point where it can replace established statistical software like R for some purposes. Artificial intelligence tools show significant promise but should still be used in conjunction with traditional methods to ensure precision in complex analysis. Consensus on the use of these tools is needed by the scientific community.

Classifying High-Frequency Oscillations by Morphologic Contrast to Background, With Surgical Outcome Correlates.

Ictal high-frequency oscillations (HFOs) are a reliable indicator of a seizure onset zone for intracranial EEG recordings. Interictal HFOs often are also observed and may be a useful biomarker to supplement ictal data, but distinguishing pathologic from physiologic HFOs continues to be a challenging task. We present a method of classifying HFOs based on morphologic contrast to the background. We retrospectively screened 31 consecutive patients who underwent intracranial recordings for epilepsy at Stanford Medical Center during a 2-year period, and 13 patients met the criteria for inclusion. Interictal EEG data were analyzed using an automated event detector followed by morphologic feature extraction and k-means clustering. Instead of only using event features, the algorithm also incorporated features of the background adjacent to the events. High-frequency oscillations with higher morphologic contrast to the background were labeled as pathologic, and "hotspots" with the most active pathologic HFOs were identified and compared with clinically determined seizure onset zones. Clustering with contrast features produced groups with better separation and more consistent boundaries. Eleven of the 13 patients proceeded to surgery, and patients whose hotspots matched seizure onset zones had better outcomes, with 4 out of 5 "match" patients having no disabling seizures at 1+ year postoperatively (Engel I or International League Against Epilepsy Class 1-2), while all "mismatch" patients continued to have disabling seizures (Fisher exact test P-value = 0.015). High-frequency oscillations with higher contrast to background more likely represent paroxysmal bursts of pathologic activity. Patients with HFO hotspots outside of identified seizure onset zones may not respond as well to surgery.

31 vs 35 mm: a randomized comparison of the pentaspline pulsed field ablation catheter sizes

Abstract Background Pulsed-Field ablation (PFA) is a non-thermal tissue-selective energy source which is increasingly used for pulmonary vein isolation (PVI). A commercially available pentaspline PFA catheter can be transformed between different configurations and is available in two different sizes – 31 and 35 mm of diameter. No clear recommendations for when to choose which catheter size are available to date. Purpose We aimed to assess procedural and outcome differences of the two different catheter sizes. Methods We prospectively included all-comer patients between 07/2022 and 01/2023 who had paroxysmal or persistent atrial fibrillation (AF) and were scheduled for PVI with PFA. There were no exclusion-criteria. 100 patients were randomly assigned to be ablated with either the 31 mm or the 35 mm pentaspline PFA catheter. Patients were routinely scheduled for follow-up visits 6 and 12 months after the ablation. Results Each group consisted of 50 patients and baseline characteristics were comparable. For the 31 mm vs 35 mm group respectively: Mean age 68.5 years vs 68.2 years, mean BMI 28.0 vs 30.3 kg/m², male sex 60% vs 68%, paroxysmal AF 59.6% vs 53.1%, mean LA diameter 40.9 vs 40.3 mm. Acute procedural efficacy defined as accomplishing PVI with the pentaspline PFA catheter was 100% in both groups. The procedural skin-to-skin time was numerically shorter in the 31 mm group (31.4 vs 34.3 minutes, p=0.11), which was attributed to a shorter ablation time (12.5 vs 15.1 minutes, p=0.052). Fluoroscopy time was significantly shorter (5.9 vs 7.1 minutes, p=0.015). The overall freedom of arrhythmia at 180 days was 82,1%. The groups show a numerical difference in freedom of arrhythmia (31 mm: 91,9% vs 35 mm: 73,4%), but no statistically significant difference using the log rank test (p=0.14, Figure 1). A total of 8 repeat procedures were performed in this patient collective for recurrent atrial arrhythmia - 3 in the 31 mm group, 5 in the 35 mm group. While the 3 repeat procedures in the 31 mm group showed no PV reconnections, 4 of the 5 patients in the 35 mm group had reconnected PVs (Fisher exact test p-Value=0.14). Overall, 25% (8/32) of PVs were reconnected, with the RSPV and RIPV being the most commonly reconnected veins (3 times each). Conclusion To the best of our knowledge, we provide the first randomized comparison of the two pentaspline PFA catheter sizes. Our data show longer procedure times and fluoroscopy times using the 35 mm device as well as a higher rate of PV reconnections especially at the septal PVs. Most importantly, we observe a trend towards worse clinical outcomes using the larger catheter. Longer follow-up times will be available at the time of presentation.Freedom from arrhythmia recurrence

Abstract PO3-11-12: A Pragmatic Randomized Trial Comparing Morning versus Evening Dosing of Endocrine Therapy for Early Breast Cancer: Final Results (REaCT-CHRONO Study)

Abstract Background. Interventions to improve tolerability and adherence to endocrine therapy (ET) are critical to the global improvement of breast cancer (BC) survivorship. The optimal time of day to take ET in terms of quality of life, side effects and adherence is unknown. This study compared a morning dose versus an evening dose of ET in patients with early-stage BC (EBC). Methods. In this pragmatic, open-label, multicenter trial, patients with hormone receptor-positive (HR+) EBC were randomized (1:1) to receive either a morning dose (within 1 hour of the patient wake up time) or an evening dose of ET (within 1 hour of patient bedtime). The primary endpoint was endocrine toxicity/tolerability measured by the change in total Functional Assessment of Cancer Therapy-Endocrine Subscale (FACT-ES) score from baseline (commencement of ET) to 12 weeks. The secondary endpoints included: ET toxicity/tolerability and quality of life (FACT-ES and FACT-B) from baseline to 4, 8, 12 and 52 weeks, non-persistence or non-adherence, and patient timing preference. Results. Between June 2021 and March 2022, 245 eligible patients were randomized, 122 to morning (122/245, 49.8%) and 123 to evening (123/245, 50.2%) dosing. Mean age was 61 [standard deviation (sd) 11.9], 181 patients (73.9%) were postmenopausal, 188 (76.7%) received tamoxifen, 58 (23.7%) received an aromatase inhibitor and 22 (9%) received luteinizing hormone-releasing hormone. The mean changes in the FACT-ES score from baseline to 12 weeks following the beginning of ET were -2.0 (sd=14.3) vs -5.4 (sd=16.8) in the morning vs evening arms respectively (Wilcoxon two-sample rank sum test p-value=0.22). Also, the proportion of patients with a clinically important increase (Fisher’s exact test p-value=0.54 0.89) or decrease (p-value= 0.89) in FACT-ES Scores was not statistically different between the arms. At 52 weeks, the mean changes in the FACT-ES score from baseline were -2.5 (sd=18.8) vs -4.8 (sd=15.5) in the morning vs evening arms respectively (p-value=0.23). There was no statistical difference in FACT-ES and FACT-B scores over the 52 weeks of the study. At 12 weeks, 94.5% (69/79) vs 98.7% (78/79) were still taking the ET (p-value=0.2), whereas at 52 weeks, 92.1% (58/63) vs 85.4% (41/48) were still taking ET (p-value=0.36), in the morning vs evening arms respectively. Also, 13.7% (10/73) vs 7.6% (6/79) and 3.2% (2/62) vs 12.5% (6/48) interrupted their ET at least once, in the morning vs evening arms, at 12 and 52 weeks respectively. At week 52, 57.9% (62/107) in the morning arm vs 13.5% (14/104) in the evening arm strongly preferred an ET morning dose, whereas 7.5% (8/107) vs 42.3% (44/104) strongly preferred an ET evening dose. No significant preference changes were observed in dose timing from baseline to week 52 (p-value=0.081). Conclusions. These results suggest no significant difference in quality of life or adherence if ET is taken in the morning or in the evening. Patients should be reassured that they can take ET at their preferred time. Clinical Trial Registration: NCT04864405 Table 1. Mean changes between FACT scores at 12 weeks and 52 weeks from baseline for patients receiving ET morning vs evening dose. A positive value indicates the FACT score increased over time. FACT ES: Endocrine Subscale; FACT B: breast Citation Format: Marie-France Savard, Mohammed Ibrahim, Gregory Pond, Deanna Saunders, Lisa Vandermeer, Lesley Fallowfield, Terry Ng, Arif Awan, Sandeep Sehdev, Ana-Alicia Beltran-Bless, Mark Clemons. A Pragmatic Randomized Trial Comparing Morning versus Evening Dosing of Endocrine Therapy for Early Breast Cancer: Final Results (REaCT-CHRONO Study) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-11-12.

OA36 Systemic juvenile idiopathic arthritis: the Great Ormond Street Hospital experience (2005-2021)

Abstract Background/Aims sJIA is a complex, systemic-inflammatory disorder. The proposed biphasic model of disease suggests that unchecked early auto-inflammation driven by increased innate immune activation, including dysregulation of IL-1 and IL-6, may lead to a state of chronic T-lymphocyte activation. This leads to an unfavourable balance of T-effector and regulatory cells that can drive chronic arthritis over time. It is therefore unsurprising that there is growing evidence to support instigation of IL-1 or IL-6 blockade as first-line treatment in sJIA. Early cytokine antagonist therapy could abrogate development of a population of these arthritis-causing T-cells to avert chronic systemic inflammation and arthritis. Aims: 1) describe clinical presentations, therapeutic interventions, complications, and remission rates at different time-points over disease course in sJIA; 2) identify potential therapeutic signals in patients with sJIA who received biologic treatment early in disease course compared to those who did not. Methods Retrospective review of all patients with sJIA at GOSH (02/10/05-21/10/21, inclusive). Data collected: patient demographics; clinical and laboratory data; treatment history; adverse events. Time-points for data collection: at diagnosis; 3-months; 1-year; last follow-up. Descriptive statistics reported as median and range or IQR for continuous variables, and as absolute frequencies and percentages for categorical variables. Comparisons of quantitative variables were made by Mann-Whitney U-test. Categorical data were compared using Fisher’s exact test (p-values<0.05 were considered significant). Results A total of 76 children (female n = 40, 53%) were diagnosed with sJIA; median age was 4.5 years (range 0.6-14.1). A biologic disease modifying anti-rheumatic drug (bDMARD) alone was commenced as first-line treatment in 28% (n = 21/76) of the cohort; however, at last review, 84% (n = 64/76) had received treatment with a bDMARD. Clinically inactive disease (CID) was achieved by 88% (n = 67/76) of the cohort at last review; however, only 32% (24/76) achieved treatment-free CID. At 1-year follow-up, CID was achieved in a significantly greater proportion of children who received treatment with a bDMARD within 3-months of diagnosis compared to those who did not (90% versus 53%, p = 0.002). Conclusion We propose a UK treatment-algorithm for children diagnosed with sJIA (see figure). We recommend reappraisal of the current NHS England commissioning policy. Disclosure C. Foley: None. D. McKenna: None. K. Gallagher: None. K. McLellan: None. H. Alkhdher: None. S. Lacassagne: None. E. Moraitis: None. C. Papadopoulou: None. C. Pilkington: None. M. Al Obaidi: None. D. Eleftheriou: None. P. Brogan: None.

Antisperm Antibody Levels After Vasectomy Reversal Are Not Associated With Pregnancy Rates or Method of Conception

ObjectiveTo examine the relationship between ASA, pregnancy rates, and method of conception following vasectomy reversal, given that before and after vasectomy reversal, patients wonder if antisperm antibodies (ASAs) will prevent them from achieving pregnancy and American Urological Association vasectomy guidelines call for additional research to answer this question. MethodsWe performed retrospective chart review and phone interview of patients who underwent vasectomy reversal at our institution from 1/1/2000 – 12/31/2018. We excluded patients who underwent vasectomy reversal for pain, or without postoperative semen analysis with ASA. We categorized patients as having low (<50%) or high (> 50%) ASA levels using the first postoperative semen analysis. Our primary outcome was pregnancy rate, including method of conception. Differences in pregnancy rates were tested using Fisher’s exact test. Results204 patients were chart reviewed. Median age at time of surgery was 40 years and median obstruction interval was 7.3 years. Median partner age was 32 years. 164 (80%) patients underwent bilateral vasovasostomy. 85 patients (42%) had low (<50%) ASA levels and 119 (58%) had high (≥ 50%) ASA levels.67 patients completed phone interviews. Of 27 men with low ASA levels, 19 (70%) achieved a pregnancy with 16 (59%) spontaneous pregnancy. Of 40 men with high ASA levels, 30 (75%) achieved a pregnancy with 16 (40%) spontaneous pregnancy. The Fisher’s exact test p-value was 0.2. ConclusionASA levels are not associated with pregnancy rate or method of conception after vasectomy reversal. These findings can improve patient counseling before and after vasectomy reversal.

The distribution of allele frequencies of the 15 Short Tandem Repeats loci in Elaziğ population, Türkiye

The DNA within the Human Genome involves loci with high polymorphism such as short tandem repeats (STR). The STR polymorphism analysis is extensively used for numerous purposes such as identification studies in forensic sciences, paternity tests, genome mapping, and population studies. In this study, blood and swab samples were obtained from 200 unrelated healthy individuals living in Elazig province. DNA was amplified via the AmpFlSTR Identifiler PCR Amplification Kit (Applied Biosystems, USA) to analyze the 15 STR loci. Using the ABI PRISM310 Genetic Analyzer capillary electrophoresis, the samples were analyzed and the allelic ladder was used to compare and identify the alleles of the samples, the distribution of the allele frequencies and peak values were examined. For statistical analysis Arlequin v.3.11 and PowerStats v.1.2 were used to assess the data. To determine if the allele frequencies were compatible with the Hardy-Weinberg (HW) equilibrium, the Markov chain and the Fisher's exact test p-value (p&lt;0.05) were examined. It was determined that the D8S1179 (0.00002), D21S11 (0.00593) and vWA (0.04939) loci were not compatible with the HW equilibrium, but the rest of the loci were compatible. For the loci, the combined power of exclusion is 0.9999995, the combined power of discrimination is 0.9999999999998. The probability of matching for the 15 STR loci was calculated to be 1 in 1.364x10ˉ17. The power of discrimination was quite high when all the loci were considered. The results of this study indicate that the populations residing in the Elaziğ province may benefit from paternity testing, forensic identification, and genomic mapping using the data as an appropriate marker.

GGC expansions in NOTCH2NLC contribute to Parkinson disease and dopaminergic neuron degeneration.

The role of GGC repeat expansions within NOTCH2NLC in Parkinson's disease (PD) and the substantia nigra (SN) dopaminergic neuron remains unclear. Here, we profile the NOTCH2NLC GGC repeat expansions in a large cohort of patients with PD. We also investigate the role of GGC repeat expansions within NOTCH2NLC in the dopaminergic neurodegeneration of SN. A total of 2,522 patients diagnosed with PD and 1,085 health controls were analyzed for the repeat expansions of NOTCH2NLC by repeat-primed PCR and GC-rich PCR assay. Furthermore, the effects of GGC repeat expansions in NOTCH2NLC on dopaminergic neurons were investigated by using recombinant adeno-associated virus (AAV)-mediated overexpression of NOTCH2NLC with 98 GGC repeats in the SN of mice by stereotactic injection. Four PD pedigrees (4/333, 1.2%) and three sporadic PD patients (3/2189, 0.14%) were identified with pathogenic GGC repeat expansions (larger than 60 GGC repeats) in the NOTCH2NLC gene, while eight PD patients and one healthy control were identified with intermediate GGC repeat expansions ranging from 41 to 60 repeats. No significant difference was observed in the distribution of intermediate NOTCH2NLC GGC repeat expansions between PD cases and controls (Fisher's exact test p-value = 0.29). Skin biopsy showed P62-positive intranuclear NOTCH2NLC-polyGlycine (polyG) inclusions in the skin nerve fibers of patient. Expanded GGC repeats in NOTCH2NLC produced widespread intranuclear and perinuclear polyG inclusions, which led to a severe loss of dopaminergic neurons in the SN. Consistently, polyG inclusions were presented in the SN of EIIa-NOTCH2NLC-(GGC)98 transgenic mice and also led to dopaminergic neuron loss in the SN. Overall, our findings provide strong evidence that GGC repeat expansions within NOTCH2NLC contribute to the pathogenesis of PD and cause degeneration of nigral dopaminergic neurons.

Cardiac function in patients with Paget disease of bone: standard and advanced echocardiographic study

Abstract Background/Introduction Paget’s disease of bone (PDB) is a common metabolic bone disorder and cardiovascular diseases are considered a possible PDB metabolic complication. Heart complications have only been described anecdotally as high-output heart failure due to high blood flow when skeletal involvement is extensive. Purpose Scientific studies that compare the structural and functional characteristics of the heart in this population are few and dated. The aims of this study were to evaluate echocardiographic parameters in PDB patients. Methods 60 PDB patients and 115 control subjects, matched by age, weight, height and history of arterial hypertension were enrolled. All subjects underwent to standard and advanced echocardiography examination. Results PBD patients showed a lower values of left ventricular ejection fraction (LVEF) (60,86 ± 4,51 vs 62,79 ± 4,30%, p 0,007), global longitudinal strain (GLS) (21,42 ± 2,20 vs 22,35 ± 2,21%, p 0,021) and myocardial work efficiency (MWE) (94,1 ± 2,0 vs 95,4 ± 2,9%, p 0,021), and higher values of interventricular septum thickness (IVSd) (9,9 ± 1,4 vs 9,1 ± 1,4 mm; p 0,003), and relative wall thickness (RWT) (0,38 ± 0,07 vs 0,35 ± 0,07, p 0,031) compared to controls, while there were no significant difference between the other parameters analyzed (Table 1). Calcification and/or sclerosis of aortic valve was detected in 26 PDB patients (43,3%) compared to 27 subjects (23,5%) in control group (Fisher’s exact test p-value = 0,006). Calcification and/or sclerosis of mitral annulus was detected in 14 PDB patients (23,3%) compared to 12 controls (11,6%) (Fisher’s exact test p-value = 0,022) (Table 2). Conclusion The study results support the hypothesis that PDB is a systemic condition, influencing cardiac function and structure, associated with increased cardiovascular risk. Our data showed that myocardial function in PDB patients is impaired. The lower resting values of LVEF, GLS and MWE represent an early subclinical myocardial damage.Table 1Table 2

Preoperative Assessment of Perianal Fistulas with Combined Magnetic Resonance and Tridimensional Endoanal Ultrasound: A Prospective Study.

we designed a prospective study of diagnostic accuracy that compared pelvic MRI and 3D-EAUS with pelvic MRI alone in the preoperative evaluation and postoperative outcomes of patients with perianal fistulas. the sample size was 72 patients and this was divided into two imaging groups. MRI alone was performed on the first group. Both MRI and 3D-EAUS were performed in parallel on the second group. Surgical exploration took place after two weeks and was the standard reference. Park's classification, the presence of a concomitant abscess or a secondary tract, and the location of the internal opening were recorded. All patients were re-evaluated for complete fistula healing and fecal incontinence six months postoperatively. All of the collected data were subjected to statistical analysis. the MRI group included 36 patients with 42 fistulas. The MRI + 3D-EAUS group included 36 patients with 46 fistulas. The adjusted sensitivity and negative predictive value were 1.00 for most fistula types in the group that underwent combined imaging. The adjusted specificity improved for intersphincteric fistulas in the same group. The adjusted balanced accuracy improved for all fistula types except rectovaginal. The combination of imaging methods showed improved diagnostic accuracy only in the detection of a secondary tract. The healing rate at six months was 100%. Fecal incontinence at six months did not present a statistically significant difference between the two groups (Fisher's exact test p-value > 0.9). Patients with complex perianal fistulas had a statistically significant higher probability of undergoing a second surgery (x2 test p-value = 0.019). the combination of pelvic MRI and 3D-EAUS showed improved metrics of diagnostic accuracy and should be used in the preoperative evaluation of all patients with perianal fistulas, especially those with complex types.

Sarcina sp. as a presumptive cause of fatal acute gastric dilation and gastric emphysema in rhesus macaques.

A 4-y-old female and 3-y-old male rhesus macaque (Macaca mulatta), both housed in the same facility, died unexpectedly within 2 wk. Postmortem examination revealed severe gastric dilation in both macaques and gastric emphysema in the female macaque. Histologically, bacteria consistent with Sarcina sp. were present in both macaques within the lungs and lumen of the trachea, esophagus, and gastrointestinal (GI) tract without associated inflammation. Additionally, in the female macaque, the bacteria were found in the gastric mucosa and associated with emphysematous spaces in the gastric wall without associated inflammation. PCR and Sanger sequencing of amplicons were subsequently performed on GI contents and non-alimentary tissues from the 2 affected monkeys and on comparative samples from unaffected rhesus monkeys in the same facility and an adjacent primate facility. The cases were compared using the 2-tailed Fisher exact test (p-value at 95% confidence). PCR identified Sarcina in GI contents of both affected and unaffected monkeys (p = 0.6084) and in non-alimentary tissues of affected monkeys only (p = 0.0083). These results suggest that the presence of Sarcina sp. in non-alimentary tissues is associated with gastric distension, gas accumulation, and unexpected death in nonhuman primates.

Abstract 6029: Multi-omic landscape of squamous cell lung cancer

Abstract Patients with squamous cell lung cancer (SCC) have high unmet medical need. Knowledge of these tumors is limited, and a lack of targetable genomic drivers means patients have few treatment options. To provide a detailed analysis on the influence of genomic alterations to proteome-level changes in SCC, we previously integrated DNA copy number, somatic mutations, RNA-sequencing, and expression proteomics in a cohort of 108 SCC patients. A major finding was identification of three proteomic subtypes, two of which made up the majority (87%) of tumors: the “Inflamed” subtype was enriched for B-cell rich tertiary lymphoid structures (TLS), and the “Redox” subtype was enriched for redox pathways and NFE2L2/KEAP1 alterations but had significantly less immune infiltration. We hypothesized these proteomic subtypes would give rise to distinct metabolic signatures. Therefore, we performed untargeted metabolomics on 87 tumors from the same cohort using chromatographic separation on a HILIC column, followed by analysis on a Q Exactive HF mass spectrometer. This analysis yielded 7,344 features corresponding to 7,072 unannotated metabolites and 272 identified metabolites. Glutathione, a key redox metabolite, was anticorrelated with immune score (R = -0.44, padj = 0.004) calculated from our transcriptomic data with the ESTIMATE algorithm, and glutathione was elevated in the Redox proteomic subtype (0.58 log2 ratio, padj = 9.87E-04). Consensus clustering was next used to identify novel metabolomic subtypes of SCC. Surprisingly, none of the five metabolomic subtypes we identified corresponded to proteomic subtype or NFE2L2/KEAP1 alteration (Fisher’s Exact test p-values &amp;gt; 0.05). The fifth subtype had 332 metabolites (26 identified) differentially expressed (&amp;gt; 1.5 fold-change, padj &amp;lt; 0.05) with ascorbate and aldarate metabolism as the top enriched pathway (padj = 3.36E-04). Interestingly, this fifth metabolomic subtype had significantly higher DNp63-alpha (p = 2.40E-05), a primary transcript of delta-N p63 that is known to promote non-small cell lung cancer. Ongoing integrative analyses across omic types will determine how p53, p63, and p73 transcripts influence these metabolomic subtypes, how these transcripts relate to the poor immune infiltration in some SCC tumors, and if these transcripts relate to novel metabolic vulnerabilities in SCC. Citation Format: Paul Stewart, Ashley Lui, Eric Welsh, Dalia Ercan, Vanessa Rubio, Hayley Ackerman, Guohui Li, Bin Fang, Steven Eschrich, John Koomen, Elsa Flores, Eric Haura, Gina DeNicola. Multi-omic landscape of squamous cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6029.

Exploring the Effects of LED-Based Visible Light Communication on Reading and Color Perception in Indoor Environments: An Experimental Study.

Visible light communications (VLC) is a technology that enables the transmission of digital information with a light source. VLC is nowadays seen as a promising technology for indoor applications, helping WiFi to handle the spectrum crunch. Possible indoor applications range from Internet connection at home/office to multimedia content delivery in a museum. Despite the vast interest of researchers in both theoretical analysis and experimentation on VLC technology, no studies have been carried out on the human perceptions of objects illuminated by VLC-based lamps. It is important to define if a VLC lamp decreases the reading capability or modifies the color perception in order to make VLC a technology appropriate for everyday life use. This paper describes the results of psychophysical tests on humans to define if VLC lamps modify the perception of colors or the reading speed. The results of the reading speed test showed a 0.97 correlation coefficient between tests with and without VLC modulated light, leading us to conclude that there is no difference in the reading speed capability with and without VLC-modulated light. The results of the color perception test showed a Fisher exact test p-value of 0.2351, showing that the perception of color is not influenced by the presence of the VLC modulated light.

Ultra-Rare Variants Identify Biological Pathways and Candidate Genes in the Pathobiology of Non-Syndromic Cleft Palate Only.

In recent decades, many efforts have been made to elucidate the genetic causes of non-syndromic cleft palate (nsCPO), a complex congenital disease caused by the interaction of several genetic and environmental factors. Since genome-wide association studies have evidenced a minor contribution of common polymorphisms in nsCPO inheritance, we used whole exome sequencing data to explore the role of ultra-rare variants in this study. In a cohort of 35 nsCPO cases and 38 controls, we performed a gene set enrichment analysis (GSEA) and a hypergeometric test for assessing significant overlap between genes implicated in nsCPO pathobiology and genes enriched in ultra-rare variants in our cohort. GSEA highlighted an enrichment of ultra-rare variants in genes principally belonging to cytoskeletal protein binding pathway (Probability Density Function corrected p-value = 1.57 × 10-4); protein-containing complex binding pathway (p-value = 1.06 × 10-2); cell adhesion molecule binding pathway (p-value = 1.24 × 10-2); ECM-receptor interaction pathway (p-value = 1.69 × 10-2); and in the Integrin signaling pathway (p-value = 1.28 × 10-2). Two genes implicated in nsCPO pathobiology, namely COL2A1 and GLI3, ranked among the genes (n = 34) with nominal enrichment in the ultra-rare variant collapsing analysis (Fisher's exact test p-value < 0.05). These genes were also part of an independent list of genes highly relevant to nsCPO biology (n = 25). Significant overlap between the two sets of genes (hypergeometric test p-value = 5.86 × 10-3) indicated that enriched genes are likely to be implicated in physiological palate development and/or the pathological processes of oral clefting. In conclusion, ultra-rare variants collectively impinge on biological pathways crucial to nsCPO pathobiology and point to candidate genes that may contribute to the individual risk of disease. Sequencing can be an effective approach to identify candidate genes and pathways for nsCPO.

314. Performance of Saliva Compared to Nasopharyngeal Swab in Detection of SARS-CoV-2 at a Field Site in Rural Guatemala Using the Roche Cobas® Liat® Point-of-Care Assay

Abstract Background Saliva samples are less invasive but not considered the gold standard for detecting SARS-CoV-2, and they are not validated for the Roche Cobas® Liat® platform. We aimed to evaluate the performance of a saliva sample compared to nasopharyngeal (NP) swab in the detection of SARS-CoV-2 on the Roche Cobas® Liat® platform at a research site in rural Guatemala. Methods Adults in an existing cohort study with influenza-like illness (ILI) provided clinical data and underwent NP swab (Copan) collection by trained nurses. Swabs were immediately placed into universal transport media (UTM), stored at 2-8 °C for less than 30 minutes and then tested on the Cobas Liat platform for SARS-CoV-2. Consenting subjects who had not eaten or drank in the last 2 hours were asked to provide a 5-mL saliva sample directly into an RNAse free container. The saliva sample remained at 2-8 °C for 24 hours, then diluted 1:2 with 0.85% saline (to reduce viscosity) and run on the same assay. We used descriptive statistics to compare the performance of saliva to NP swabs. Results Of the 28 subjects screened (1/10/22 - 4/26/22), 23 (82%) were consented and enrolled. The majority of subjects were male (78.3%) with a mean age of 31 years (range: 18-59 years). Of the 23 subjects enrolled, 14 (30.4%) reported fever and cough, 16 (34.8%) reported cough only, 14 (30.4%) reported fever only, and 2 (4.3%) reported cough and nasal congestion. The median symptom duration was 3.0 days (IQR: 1.5-5 days). Of the 23 subjects, 5 (23.7%) tested positive for SARS-CoV-2 in both sample types (NP swab and saliva); 3 (13%) were discordant, including 1 (4.3%) saliva-positive only and 2 (8.7%) NP-positive only. Compared to NP swab, preliminary performance of saliva in detection of SARS-CoV-2 included a sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 71.4%, 93.7%, 87%, 83.3%, and 88.2%, respectively. The Fisher’s exact test p-value (0.003) shows concordance between both tests. Conclusion Our preliminary results show good precision between NP and saliva samples in detection of SARS-CoV-2 on the Roche Cobas® Liat® platform. Ongoing data collection will provide greater insight on the discordant results, but our findings support the continued use of saliva in the detection of SARS-CoV-2 in this population. Disclosures Molly Lamb, PhD, Pfizer: Grant/Research Support Edwin J. Asturias, MD, Curevac: DSMB Member|Fundacion para la Salud Integral de los Guatemaltecos: Board Member|Inovio: DSMB Member|Merck: Honoraria|Pfizer: Grant/Research Support Diva Calvimontes, n/a, Pfizer: Grant/Research Support Daniel Olson, MD, Fundacion para la Salud Integral de los Guatemaltecos: Board Member|Pfizer: Grant/Research Support|Roche: Grant/Research Support.

Non-Safety and Safety Device Sharp Injuries-Risk of Incidents, SEDs Availability, Attitudes and Perceptions of Nurses According to Cross-Sectional Survey in Poland.

Sharp injuries are a serious issue among healthcare workers (HCWs). The aim of the study was to examine the frequency of sharps injuries among nurses (who have the most frequent contact with infectious material) when using devices with and without safety features, then to analyse the factors associated with such injuries and to compare the risk of injuries with safety engineered devices (SEDs) and non-safety engineered devices (non-SEDs). An online cross-sectional survey was completed between October 2021 and March 2022 by 280 nurses. The incidence of exposure to sharp injury during their professional life was 51.4%. The percentage of nurses experiencing a sharp injury in the year preceding the study was 29% and 9.6% for superficially and deep injury, respectively. Ampoules and conventional hollow-bore needles caused the most injuries (25.92% and 22.64% of nurses in the last year). Factors including sex (males), age and seniority (elderly), education (higher), work exhaustion and being left-handed were associated with the occurrence of conventional hollow-bore needle injuries. In the case of SEDs: age, seniority and right/left-handed were the most frequent risk factors associated with the occurrence of sharp injuries. SEDs injuries were much less frequent than non-SEDs. There was a significant difference between the risk of injuries with safety and non-safety needles, central cannulas and ampoules. Fisher’s exact test (p-value = 0.000) and positive Spearman’s rho statistics (0.2319, p-value = 0.0001) confirmed that in accredited hospitals, the availability of safety needles was higher. Almost half of the nurses (n = 115, 41.07%) stated that staff had little influence on the type of medical sharp instruments supplied. To reduce the risk of nurse injuries, access to medical devices with safe protection mechanisms should be ensured, the use of sharp instruments should be limited where possible, managers should consult nurses regarding the choice of safe devices, and training programs on the proper use of SEDs should be available.

Gender dysphoria in twins: a register-based population study

Both genetic and environmental influences have been proposed to contribute to the variance of gender identity and development of gender dysphoria (GD), but the magnitude of the effect of each component remains unclear. We aimed to examine the prevalence of GD among twins and non-twin siblings of individuals with GD, using data derived from a large register-based population in Sweden over the period 2001–2016. Register data was collected from the Statistics Sweden and the National Board of Health and Welfare. The outcome of interest was defined as at least four diagnoses of GD or at least one diagnosis followed by gender-affirming treatment. A total of 2592 full siblings to GD cases were registered, of which 67 were twins; age at first GD diagnosis for the probands ranged from 11.2 to 64.2 years. No same-sex twins that both presented with GD were identified during the study period. The proportion of different-sex twins both presenting with GD (37%) was higher than that in same-sex twins (0%, Fisher’s exact test p-value < 0.001) and in non-twin sibling pairs (0.16%). The present findings suggest that familial factors, mainly confined to shared environmental influences during the intrauterine period, seem to contribute to the development of GD.

The value of eosinophil count in the diagnosis of preeclampsia among pregnant women attending the University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia, 2021

BackgroundCurrently, studies showed that eosinophil count had clinical significance in the diagnosis and prognosis of diseases. But, the clinical significance of eosinophil count in pregnancy specifically in preeclampsia (PE) is not well studied. The main objective of the present study was to assess the diagnosis value of eosinophils counts among pregnant women with PE.MethodsA comparative cross-sectional study was conducted on a total of 126 pregnant women at the University of Gondar Comprehensive Specialized Hospital, using a convenient sampling technique. Socio-demographic and clinical data were collected by questionnaire and datasheet from patient’s charts, respectively. A total of six ml of blood was collected from each study participant; three ml for complete cell count analysis using Sysmex XS-500i hematology analyzer and three ml for liver function tests using Humastar 200 chemistry analyzer. The data were entered into Epi-data and exported to SPSS 20 for analysis. The independent t-test was used for normally distributed data and, the Mann–Whitney U test was used for non-normally distributed data. Binary logistic regression and receiver operative curve analyses were also done to assess the diagnosis value of eosinophils count. P-value < 0.05 was considered statistically significant.ResultsThe eosinophils count of PE pregnant women were significantly lower than the normotensive (NT) pregnant women (median (IQR): 50 (10—200) vs. 120 (60 – 270); (p = 0.002). The eosinophil count ≤ 55 cells/µL had an AUC of 0.66 (95% CI; 0.56—0.75) for diagnosis of PE with a sensitivity of 50.8%, specificity of 77.8%, and positive and negative predictive value of 69.6% and 61.3%, respectively. The abnormal AST and ALT results were significantly higher among PE pregnant women compared to NT pregnant women (AOR: 14.86; 95% CI: 4.97—44.4 and Fischer exact test p-value = 0.001, respectively).ConclusionThe eosinophil count ≤ 55cells/µl had a reasonable/acceptable AUC which may use in the diagnosis of PE. AST and ALT were also significantly higher in PE pregnant women compared to NT pregnant women. Multicenter longitudinal studies with a large sample size are recommended to verify the role of eosinophil count in the diagnosis of PE.

Oral Hygiene Habits and Use of Fluoride in Developmental Age: Role of Parents and Impact on their Children.

Introduction In healthcare, the need to pay more attention to the achievement of two objectives within the society arises: health promotion and prevention in terms of nutrition, good education, sport, and health education. Scientific evidence shows that adequate health standards must be learned since childhood through the help of parents and appropriate school projects. Parental intervention must be appropriate to support the responsibility of their children's health. In oral health, it has been established for many years that there is a correlation between parental behaviors and lifestyles and children's attitude. The aim of this study is to verify the close relation between behaviors, habits, lifestyles, and the knowledge of parents about their oral health and, consequently, their focus and care for their own children's oral health. Furthermore, the awareness of parents about the importance and use of fluorine was to be determined. Materials and Methods The study lasted 15 months and was conducted from April 2018 to July 2019: an anonymous 29-question questionnaire was administered to all parents who accompanied their children (aged between 3 and 12 years) going under treatment in the Pediatric Dentistry Unit of the University Hospital Policlinico Umberto I, Rome. Anamnestic data, sociodemographic context (e.g., educational level and occupation), oral health habits, and prevention of parents and children and fluoride knowledge were investigated. The study received ethical approval. 204 questionnaires were collected. The data gathered were recorded with a specifically designed computer program and collected and analyzed using a Microsoft Excel 10 database. Data were evaluated using standard statistical analysis software; descriptive statistics including mean ± SD values and percentage were calculated for each variable. The relationship between the age of parents, between mother or father and the parents' degree of education levels, and the knowledge for their own children's oral health was explored using the chi-square test of homogeneity and Fisher's exact test (P value of < 0.05 considered as statistically significant). Results From the acquired data, it is possible to deduce that the major respondents were mothers aged from 36 to 45, while only a small part were fathers aged above 45 years. Questions related to parents' oral hygiene habits were included in the questionnaire, and from the sample taken into consideration, it emerges that 64.7% of the respondents (67.1% mothers and 57.7% fathers) periodically attend a dental office for a checkup, 20.9% tend to postpone the treatment, and 15.2% go there just for emergency. Some of the questions showed that 80% of the interviewed subjects use fluoride toothpaste for their child's oral hygiene. Conclusion Prevention in childhood, in addition to being synonymous with monitoring the oral health of the child, means first of all to pay attention to parents who are the main behavioral reference. It emerged that there is no adequate knowledge about fluorine, especially when the subjects have a low educational level. A role of fundamental importance for the diffusion of adequate concepts in the field of oral hygiene is covered, according to the data received from the study carried out, by the dentist and dental hygienist.

A transcriptomic signature for prostate cancer relapse prediction identified from the differentially expressed genes between TP53 mutant and wild-type tumors

For prostate cancer (PCa) patients, biochemical recurrence (BCR) is the first sign of disease relapse and the subsequent metastasis. TP53 mutations are relatively prevalent in advanced PCa forms. We aimed to utilize this knowledge to identify robust transcriptomic signatures for BCR prediction in patients with Gleason score ≥ 7 cancers, which cause most PCa deaths. Using the TCGA-PRAD dataset and the novel data-driven stochastic approach proposed in this study, we identified a 25-gene signature from the genes whose expression in tumors was associated with TP53 mutation statuses. The predictive strength of the signature was assessed by AUC and Fisher’s exact test p-value according to the output of support vector machine-based cross validation. For the TCGA-PRAD dataset, the AUC and p-value were 0.837 and 5 × 10–13, respectively. For five external datasets, the AUCs and p-values ranged from 0.632 to 0.794 and 6 × 10–2 to 5 × 10–5, respectively. The signature also performed well in predicting relapse-free survival (RFS). The signature-based transcriptomic risk scores (TRS) explained 28.2% of variation in RFS on average. The combination of TRS and clinicopathologic prognostic factors explained 23–72% of variation in RFS, with a median of 54.5%. Our method and findings are useful for developing new prognostic tools in PCa and other cancers.