Impaired Cardiorespiratory Fitness of Elite Athletes after Asymptomatic or Mild SARS-CoV-2 Infection.

Background and Objectives: The aim of the study was to evaluate the health status of professional athletes after recovering from COVID-19 and the impact that SARS-CoV-2 had on their overall cardiorespiratory fitness, which was done by conducting cardiopulmonary exercise testing (CPET). Materials and Methods: A total of twenty-seven professional basketball players (Euroleague Basketball and the ABA League) participated in the study. CPET was performed before (as part of their regular preparticipation exam, during the pre-season period), as well as after SARS-CoV-2 infection (after two weeks of home isolation, during the competitive part of the season). CPET was performed on a treadmill, while cardiovascular, respiratory, and metabolic functions were evaluated by using a breath-by-breath analysis technique (Quark CPET system manufactured by Cosmed, Rome, Italy). Results: Maximal oxygen consumption and aerobic efficiency were significantly reduced after SARS-CoV-2 infection (p = 0.000). An obvious decrease in oxygen pulse was observed during CPET after recovering from COVID-19 (p = 0.001), as was deterioration of ventilatory efficiency. Internal respiration was the most negatively affected. An early transition from aerobic to anaerobic mechanisms of creating energy for work and intensive metabolic fatigue were obvious after SARS-CoV-2 infection. Conclusions: Although it was believed that SARS-CoV-2 only affects the cardiopulmonary status of the elderly population and people with associated comorbidities, it is clear from this research that professional athletes can also be at certain risk. Even though no pathological cardiovascular and respiratory changes were found in athletes after COVID-19, results showed significantly decreased cardiorespiratory fitness, with an emphasis on internal respiration.

Running Variability in Marathon-Evaluation of the Pacing Variables.

Background and Objectives: Pacing analyses for increasingly popular long-distance running disciplines have been in researchers' spotlight for several years. In particular, assessing pacing variability in long-distance running was hardly achievable since runners must repeat long-running trials for several days. Potential solutions for these problems could be multi-stage long-distance running disciplines. Therefore, this study aimed to assess the long-distance running variability as well as the reliability, validity, and sensitivity of the variables often used for pacing analyses. Materials and Methods: This study collected the split times and finish times for 20 participants (17 men and three women; mean age 55.5 years ± 9.5 years) who completed the multiday marathon running race (five marathons in 5 days), held as part of the Bretzel Ultra Tri in Colmar, France, in 2021. Seven commonly used pacing variables were subsequently calculated: Coefficient of variation (CV), Change in mean speed (CS), Change in first lap speed (CSF), Absolute change in mean speed (ACS), Pace range (PR), Mid-race split (MRS), and First 32 km-10 km split (32-10). Results: Multi-stage marathon running showed low variability between days (Intraclass correlation coefficient (ICC) > 0.920), while only the CV, ACS, and PR variables proved to have moderate to good reliability (0.732 < ICC < 0.785). The same variables were also valid (r > 0.908), and sensitive enough to discern between runners of different performance levels (p < 0.05). Conclusions: Researchers and practitioners who aim to explore pacing in long-distance running should routinely utilize ACS, CV, and PR variables in their analyses. Other examined variables, CS, CSF, MRS, and 32-10, should be used cautiously. Future studies might try to confirm these results using different multi-stage event's data as well as by expanding sensitivity analysis to age and gender differences.

Structural Transitions of Papain-like Cysteine Proteases: Implications for Sensor Development.

The significant role of papain-like cysteine proteases, including papain, cathepsin L and SARS-CoV-2 PLpro, in biomedicine and biotechnology makes them interesting model systems for sensor development. These enzymes have a free thiol group that is suitable for many sensor designs including strong binding to gold nanoparticles or low-molecular-weight inhibitors. Focusing on the importance of the preservation of native protein structure for inhibitor-binding and molecular-imprinting, which has been applied in some efficient examples of sensor development, the aim of this work was to examine the effects of the free-thiol-group's reversible blocking on papain denaturation that is the basis of its activity loss and aggregation. To utilize biophysical methods common in protein structural transitions characterization, such as fluorimetry and high-resolution infrared spectroscopy, low-molecular-weight electrophilic thiol blocking reagent S-Methyl methanethiosulfonate (MMTS) was used in solution. MMTS binding led to a two-fold increase in 8-Anilinonaphthalene-1-sulfonic acid fluorescence, indicating increased hydrophobic residue exposure. A more in-depth analysis showed significant transitions on the secondary structure level upon MMTS binding, mostly characterized by the lowered content of α-helices and unordered structures (either for approximately one third), and the increase in aggregation-specific ß-sheets (from 25 to 52%) in a dose-dependant manner. The recovery of this inhibited protein showed that reversibility of inhibition is accompanied by reversibility of protein denaturation. Nevertheless, a 100-fold molar excess of the inhibitor led to the incomplete recovery of proteolytic activity, which can be explained by irreversible denaturation. The structural stability of the C-terminal ß-sheet rich domain of the papain-like cysteine protease family opens up an interesting possibility to use its foldamers as a strategy for sensor development and other multiple potential applications that rely on the great commercial value of papain-like cysteine proteases.

Intravenous versus subcutaneous delivery of biotherapeutics in IBD: an expert's and patient's perspective.

Several biologic treatments are available in addition to intravenous also in subcutaneous form for treatment of chronic diseases. Benefits of the subcutaneous application of drugs include self-administration by the patient, shorter time of application process with less infusion related adverse events and consequently lower healthcare costs. With appropriate education and support patients are able to administer their treatments at home. This leads to improvement of quality of life, reduction of time needed to travel to the healthcare institution and consequently also reduces costs also for the patient.Over one million residents in the USA and 2.5 million in Europe are estimated to have inflammatory bowel disease (IBD), with substantial costs for health care. These estimates do not factor in the 'real' price of IBD, which can impede career aspirations, instil social stigma and impair quality of life in patients.The Virtual Community Meeting, which offered an exchange of experience and opinions from healthcare professionals who are active in treating IBD, and patients with this chronic disease, revealed in-depth arguments and answers to some essential questions: which patients prefer subcutaneous over intravenous dosing; which patients continue to favour intravenous infusions; what are the limitations regarding both applications; what is the patient's role in therapeutical decision-making and how does IBD affect the patient's work, finances and quality of life? The aim of this article is to discuss the differences between subcutaneous and intravenous dosing from the health-economic, scientific, and personal perspectives.The meeting offered strong confirmation that most of the patients and healthcare professionals prefer subcutaneous over intravenous drug administration but emphasise the management of risks associated with treatment compliance. Patient education provided by the IBD team in this regard is mandatory. Quality of life of patients is poorer during active disease, but the findings that it can improve over time, including as a result of home- or self-administration of biologics, may be encouraging for individuals with this chronic disease.

Infliximab Rescue in Acute Severe Ulcerative Colitis Complicated by Clostridium Difficile Infection: A Case Series.

Relapses in inflammatory bowel disease (IBD) complicated by Clostridium difficile infection (CDI) are associated with significant morbidity and mortality. CDI can exacerbate the course of IBD and may result in prolonged hospitalizations, admissions to intensive care, surgical interventions, or even death. Early detection and aggressive treatment with systemic corticosteroids or biologics such as infliximab are often needed in severe presentations. Five cases of relapsed ulcerative colitis complicated by fulminant CDI were retrospectively reviewed. Biological therapy with infliximab was initiated upon multidisciplinary team assessment as the cases were resistant to standard IBD therapy. All five patients improved clinically and avoided early surgical intervention. Some required prolonged therapy with infliximab to achieve remission. Early recognition of CDI and aggressive therapy with biologics may be required to avoid complications in the IBD patients experiencing a relapse. Infliximab therapy should be considered early on, especially where the disease is resistant to standard therapy.

Age Differences in Pacing in Endurance Running: Comparison between Marathon and Half-MarathonMen and Women.

BACKGROUND AND OBJECTIVE: The increased popularity of marathons and half-marathons has led to a significant increase in the number of master runners worldwide. Since the age-related decrease in performance is dependent on race duration, pacing in long distance running might also vary by race distance in both men and women. Therefore, the main aim of this study was to assess pacing differences between marathon and half-marathon runners with regard to the runners' age group, and independently for men and women. MATERIALS AND METHODS: In total, 17,465 participants in the Vienna City marathon in 2017 were considered for this study (marathon, N = 6081; half-marathon, N = 11,384). Pacing was expressed as two variables (i.e., pace range and end spurt). RESULTS: All runners showed positive pacing strategies (i.e., a fast start with gradual decrease of speed). However, marathon runners showed greater variability in pacing than half-marathon runners. Furthermore, women showed no differences in pace variability in regard to the age group, whereas men younger than 30 years of age, as well as older men (over the age of 60), showed a greater variability in pace than other age groups. Finally, younger half-marathon men and women showed the fastest end spurt compared to older age groups and marathon runners. CONCLUSIONS: The presented findings could help sports and medicine practitioners to create age specific training plans and pacing strategies. This approach could help long distance runners to improve their physical fitness, achieve better race times, reduce the potential risk of musculoskeletal injuries and increase the overall pleasure of long distance running.

Impact of Differences in Economic Development and Socioeconomic Stability on Benzodiazepine Exposure between the Three Balkans Countries.

INTRODUCTION: Anxiety disorders are among the most common mental disorders. Benzodiazepines belong to the group of anxiolytic sedatives and the most prescribed drugs in the world. The aim in ours study was to evaluate the differences in the exposure of the population to benzodiazepines (in period from 2014-2018) between Serbia, Slovenia and Croatia, the three countries of the Southwestern Balkans with varying degrees of socioeconomic development. STUDY DESIGN: A academic investigator initiated, pharmacoepidemiological difference-in-difference time series analysis of population exposure to benzodiazepines between the three, geographically close Balkans countries (Slovenia, Serbia, Croatia) with varying degrees of socioeconomic development has been carried out. Study was conducted as academic investigator initiated, in a retrospective manner on monthly basis international data set from January 2014 to December 2018. RESULTS: At the annual level, during the study period from January 2014 to December 2018, compared to Slovenia, Serbia and Croatia had higher DIDs, from 5 fold (Croatia) to 6 fold (Serbia), for all benzodiazepines in total. By analyzing the differences-in-difference, we have shown that influence of both time (month) and country on DIDs is significant as well as their mutual interaction (the country x month) for all benzodiazepines in total. CONCLUSION: Serbia and Croatia must implement explicit measures of reducing benzodiazepine prescription in health primary care based on evidence-based recommendations in the indications where general medicine practitioners/family doctors most commonly prescribe these medicines. Without providing a realistic supplement/alternative to benzodiazepines such as increasing the availability of psychotherapy and improving the structure of psychiatric professionals in healthcare settings, implicit measures are not recommended for reducing prescription, implementing accountability measures for prolonged prescription of benzodiazepines, and in particular for "masked" somatic diseases. All this comes to the fore by raising economic development and socioeconomic stability.

Case Report: Acute Flair of Ulcerative Colitis during Pregnancy Is Still a Major Problem.

Although severe flare of ulcerative colitis (UC) is uncommon, it significantly increases the risk of preterm delivery, low birth weight and other adverse fetal outcomes. It is critical to optimize aggressive medical treatment with both mother and fetal health. Here, we present a case of a 30-year-old woman with a severe flare of UC at the 16th gestational week. The diagnosis of extensive UC was established 8 years ago. From the time she was diagnosed, she had 5 moderate flares successfully treated with oral and topical mesalamine. The relapses of disease occurred due to poor adherence to maintenance therapy. The patient had a positive family history for UC and thrombophilia (factor V Leiden mutations). At the time of admission, she presented with 8-10 bloody diarrheas and moderate abdominal pain. She was afebrile with increased heart rate (96/min). Laboratory studies showed elevated C-reactive protein (CRP, 42 mg/l), fecal-calprotectin (7,223 µg/g), and anemia (hemoglobin 10.4 g/dl). Clostridium difficile and CMV infection were excluded. Intensive treatment with systemic steroids and low-molecular weight heparin was started. Three days later, no response to the therapy was observed (8 bloody stools, CRP 40 mg/l). According to emergency symptoms, rescue therapy with infliximab (IFX; 5 mg/kg standard induction protocol) was administered a week later. A partial clinical and laboratory response was achieved after the second dose of IFX (4 stools/day, CRP 12.2 mg/l and FCP 1,078 µg/g). The patient received the third and least doses of IFX at the 23rd gestational week. She continued on corticosteroids and mesalamine with chronically active moderate disease. IFX trough levels before the third dose were 20.6 µg/ml; antibodies to IFX were negative. The patient delivered trans-vaginally a healthy girl on the 36th gestational week (the newborn weight: 3,150 kg, APGAR score 9). No live vaccines were administrated to the newborn until 6 months of age.

Current trends in clinical genetics of colorectal cancer.

Recent innovations in molecular biology and colorectal cancer (CRC) genetics have facilitated the understanding of the pathogenesis of sporadic and hereditary CRC syndromes. The development of technology has enabled data collection for a number of genetic factors, which lead to understanding of the molecular mechanisms underlying CRC. The incidence and the nature of CRC is a mixture of genetic and environmental factors. The current field of interest is to understand how molecular basis could shape predisposition for developing CRC, disease progression and response to chemotherapy. In this article, we summarize new and developing genetic markers, and assess their clinical value for inherited and sporadic CRC.

Can didactic continuing education improve clinical decision making and reduce cost of quality? Evidence from a case study.

INTRODUCTION: Administration of human serum albumin (HSA) solutions for the resuscitation of critically ill patients remains controversial. The objective of this study was to assess the effect of continuing medical education (CME) on health care professionals' clinical decision making with regard to HSA administration and the costs of quality (COQ). A quasi-experimental study of time series association of CME intervention with COQ and use of HSA solution was conducted at the Surgery Department of the Hospital Valjevo, Serbia. The CME contained evidence-based criteria for HSA solution administration in surgical patients. The preintervention period was defined as January 2009 to May 2011. CME was provided in June 2011, with the postintervention period June 2011 to May 2012. METHODS: Total mortality rate, the rate of nonsurgical mortality, the rate of surgical mortality, the rate of sepsis patient mortality, index of irrational use of HSA solutions, and number of hospital days per hospitalized patient were collected for each month as quality indicators. Statistical analysis was performed by multivariate autoregressive integrated moving average (MARIMA) modeling. The specification of the COQ was performed according to a traditional COQ model. RESULTS: The CME intervention resulted in an average monthly reduction of the hospital days per hospitalized patient, the rate of sepsis patient mortality, index of irrational use of HSA solutions, and COQ for $593,890.77 per year. DISCUSSION: Didactic CME presenting evidence-based criteria for HSA administration was associated with improvements in clinical decisions and COQ. In addition, this study demonstrates that models combining MARIMA and traditional COQ models can be useful in the evaluation of CME interventions aimed at reducing COQ.

The relationship between hip, knee and ankle muscle mechanical characteristics and gait transition speed.

The purpose of the present study was to explore the relationship between mechanical characteristics of hip, knee and ankle extensor and flexor muscle groups and gait transition speed. The sample included 29 physically active male adults homogenized regarding their anthropometric dimensions. Isokinetic and isometric leg muscle mechanical characteristics were assessed by an isokinetic dynamometer, while individual walk-to-run (WRT) and run-to-walk transition speeds (RWT) were determined using the standard increment protocol. The relationship between transition speeds and mechanical variables scaled to body size was determined using Pearson correlation and stepwise linear regression. The highest correlations were found for isokinetic power of ankle dorsal flexors and WRT (r=.468, p<.01) and the power of hip extensors and RWT (r=.442, p<.05). These variables were also the best predictors of WRT and RWT revealing approximately 20% of explained variance. Under the isometric conditions, the maximal force and rate of force development of hip flexors and ankle plantar flexors were moderately related with WRT and RWT (ranged from r=.340 to .427). The only knee muscle mechanical variable that correlated with WRT was low velocity knee flexor torque (r=.366, p<.05). The results generally suggest that the muscle mechanical properties, such as the power of ankle dorsal flexors and hip extensors, influence values of WRT and RWT.

Body size and countermovement depth confound relationship between muscle power output and jumping performance.

A number of studies based on maximum vertical jumps have presumed that the maximum jump height reveals the maximum power of lower limb muscles, as well as the tested muscle power output predicts the jumping performance. The objective of the study was to test the hypothesis that both the body size and countermovement depth confound the relationship between the muscle power output and performance of maximum vertical jumps. Sixty young and physically active males were tested on the maximum countermovement (CMJ) and squat jumps (SJ). The jumping performance (Hmax), peak (Ppeak) and the average power output (Pavg) during the concentric phase, countermovement depth (only in CMJ) and body mass as an index of body size were assessed. To assess the power-performance relationship, the correlations between Hmax with both Ppeak and Pavg were calculated without and with controlling for the effects of body mass, as well as for the countermovement depth. The results revealed moderate power-performance relationships (range .55

Microsatellite instability affecting the T17 repeats in intron 8 of HSP110, as well as five mononucleotide repeats in patients with colorectal carcinoma.

AIM: To investigate mononucleotide markers: BAT-25, BAT-26, NR-21, NR-22 and NR-24 in patients with colorectal cancer (CRC), and the status of HSP110T17, KRAS, BRAF and the MLH1 promoter mutations in microsatellite unstable CRC. METHODS: Genetic assessments were performed on samples obtained following resection of CRC in 200 patients. RESULTS: Allelic variations of HSP110T17 were found in all 18 patients with microsatellite instabilities (MSIs) in at least three markers (high-frequency MSI). By contrast, mutations of HSP110T17 were absent in all 20 patients with no MSI frequency. Eight out of 182 patients with low (instability in one marker) or no frequency MSI had allelic shifts due to polymorphisms of BAT-25 (1.5%), NR-21 (1.75%) and NR-24 (1.5%). BRAF mutations were associated with >5 bp shortening of HSP110T17. CONCLUSION: Patients with high-frequency MSI CRC had allelic variations of HSP110T17. BRAF mutations occur along with greater shortening in HSP110T17 during oncogenesis via the MSI pathway.

Jump training with different loads: effects on jumping performance and power output.

PURPOSE: To investigate the selective effects of different types of external loads applied in vertical jump training on both the performance and muscle power output of the squat (SJ) and countermovement jump (CMJ). METHODS: Physically active males practiced maximum unconstrained vertical jumps over an 8-week period with no load, with either a negative or positive load exerted by a nearly constant external force that altered their body weight, and with a loaded vest that increased both the body weight and inertia. The magnitude of all applied loads corresponded to 30 % of body weight. RESULTS: A similar training-associated increase in jump height was observed in all experimental groups in both CMJ (7.4-11.8 %) and SJ (6.4-14.1 %). The relative increase in power output was comparable to the increase in jump height in SJ (7.4-11.5 %), while the power increase in CMJ was relatively small and load-specific (0.5-9.5 %). The observed differences could originate from the changes in the CMJ pattern, reflected through the depth of the counter movement that particularly increased after the training with negative load (42 %) and no load (21 %). The same participants also revealed increased CMJ duration, reduced ground reaction forces, as well as reduced maximum and average power output when compared with other training groups. CONCLUSION: Jump training with the applied loads could lead to a comparable improvement in jumping performance. However, the observed load-specific adaptations of CMJ pattern could decouple the training-associated increase in jump height from the increase in muscle power output.

Serotonergic organization of the central nervous system.

The last 50 years of researches of biochemism and the CNS functionality are intensively engaged in studying the role of monoamine neurotramsmitter serotonin (5-hydroxytryptamin) (5-HT). The serotonergic receptors function depends on spot where the receptor function, the dynamic relationship with other transmitters and stimulation that can activate or inhibit specific neurons. The results of research in biochemistry, neurophysiology and neuroradiology have provided insight into the complexity of the operation of key structures such as the amygdala, prefrontal cortex and hippocampus, whose role varies depending on the received external impulses and the impulses that are sent to relevant areas. This implies that the transmitters and especially 5-HT, have much wider effects that are determined not to structures but by the impulse dynamics. It also means that psychopharmaceutical drugs whose therapeutic effect is based on the change of the concentration of serotonin in the synapse and the postsynaptic receptors depending on where they operate, have an effect on affective or cognitive symptoms. Serotonergic antidepressants by changing the concentration of serotonin change primarily affective manifestations but also they have significant influence on all the spectrum of serotonergic disorders not only emotional, but also the cognitive level, which is also a confirmation that the therapeutic effects do not depend only on the simple change of serotonin concentration but also of the level where these changes occur in dynamic comparison of key transmitters. Atypical antipsychotics which have low affinity for dopaminergic and high affinity for serotonergic receptors are seen through the dynamic relationship of serotonin, dopamine and noradrenalin in nigrostriatal, mezocortical, mezolimbic and tuberoinfudibular pathways.

Clinical and pathological tools for identifying microsatellite instability in colorectal cancer.

AIM: To assess practical accuracy of revised Bethesda criteria (BGrev), pathological predictive model (MsPath), and histopathological parameters for detection of high-frequency of microsatellite instability (MSI-H) phenotype in patients with colorectal carcinoma (CRC). METHOD: Tumors from 150 patients with CRC were analyzed for MSI using a fluorescence-based pentaplex polymerase chain reaction technique. For all patients, we evaluated age, sex, family history of cancer, localization, tumor differentiation, mucin production, lymphocytic infiltration (TIL), and Union for International Cancer Control stage. Patients were classified according to the BGrev, and the groups were compared. The utility of the BGrev, MsPath, and clinical and histopathological parameters for predicting microsatellite tumor status were assessed by univariate logistic regression analysis and by calculating the sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values. RESULTS: Fifteen out of 45 patients who met and 4 of 105 patients who did not meet the BGrev criteria had MSI-H CRC. Sensitivity, specificity, PPV, and NPV for BGrev were 78.9%, 77%, 30%, and 70%, respectively. MSI histology (the third BGrev criterion without age limit) was as sensitive as BGrev, but more specific. MsPath model was more sensitive than BGrev (86%), with similar specificity. Any BGrev criterion fulfillment, mucinous differentiation, and right-sided CRC were singled out as independent factors to identify MSI-H colorectal cancer. CONCLUSION: The BGrev, MsPath model, and MSI histology are useful tools for selecting patients for MSI testing.

High-frequency microsatellite instability and BRAF mutation (V600E) in unselected Serbian patients with colorectal cancer.

Microsatellite instability (MSI) is a genetic consequence of a MisMatch Repair defect in colorectal cancer (CRC). We compared clinicopathohistological features with MSI status of CRC and evaluated prognostic significance of MSI status and BRAF mutation in the group of MSI-H tumors. 155 primary CRCs were excised surgically, 2006-2008. MSI analysis was carried out using a fluorescence-based pentaplex polymerase chain reaction technique. BRAF mutation (V600E) was analyzed by direct sequencing in MSI-H tumors. For all patients were evaluated: age, gender, localization, tumor cell type, tumor differentiation, mucin production, lymphocytic infiltration (TILs) and TNM stage. Patients' disease-free survival (DFS) was compared according to MSI and BRAF status using Kaplan-Meier test. Of the 155 CRCs, 19 (12.3%) were MSI-H, and 136 (87.7%) were MSS/L. BRAF mutations were found in 4 of the MSI-H tumors. Patients with MSI-H CRC had lower recurrence rate (log rank test; P = 0.04) than MSS/L group. Patients with MSI-H tumor and BRAF mutation had worse DFS than MSI-H tumors without this mutation (log rank test; P = 0.01). Most of the clinicopathologic characteristics of MSI-H CRC in Serbian patients are similar to those reported in previous studies. Patients with MSI tumor phenotype had favourable prognosis, but in those with BRAF mutation higher recurrence rate was observed.

Oral squamous cell carcinoma detection by salivary biomarkers in a Serbian population.

Early detection of oral squamous cell cancer (OSCC) is the key to improve the low 5-year survival rate. Using proteomic and genomic technologies we have previously discovered and validated salivary OSCC markers in American patients. The question arises whether these biomarkers are discriminatory in cohorts of different ethnic background. Six transcriptome (DUSP1, IL8, IL1B, OAZ1, SAT1, and S100P) and three proteome (IL1B, IL8, and M2BP) biomarkers were tested on 18 early and 17 late stage OSCC patients and 51 healthy controls with quantitative PCR and ELISA. Four transcriptome (IL8, IL1B, SAT1, and S100P) and all proteome biomarkers were significantly elevated (p<0.05) in OSCC patients. The combination of markers yielded an AUC of 0.86, 0.85 and 0.88 for OSCC total, T1-T2, and T3-T4, respectively. The sensitivity/specificity for OSCC total was 0.89/0.78, for T1-T2 0.67/0.96, and for T3-T4 0.82/0.84. In conclusion, seven of the nine salivary biomarkers (three proteins and four mRNAs) were validated and performed strongest in late stage cancer. Patient-based salivary diagnostics is a highly promising approach for OSCC detection. This study shows that previously discovered and validated salivary OSCC biomarkers are discriminatory and reproducible in a different ethnic cohort. These findings support the feasibility to implement multi-center, multi-ethnicity clinical trials towards the pivotal validation of salivary biomarkers for OSCC detection.