Tapping Scores Research Articles

Complex decongestive therapy improves finger tapping score in patients with breast cancer-related lymphedema.

Breast cancer-related lymphedema (BCRL) impairs upper limb function and cognitive performance. This study aimed to evaluate the effects of fifteen sessions of complex decongestive therapy (CDT) on fine motor performance and information processing speed in women with BCRL. Thirty-eight women with BCRL (54.97 ± 10.78years) were recruited in the study. Participants either received five times weekly CDT consisting of manual lymphatic drainage, skin care, compression bandaging, and remedial exercises (n = 19) or served as a wait-list control group (n = 19). We used the Finger Tapping Task to assess fine motor performance and the Digit Symbol Substitution Test to assess information processing speed. ANCOVA was performed to analyze the effect of CDT on the dependent variables, adjusting for covariates and baseline values. CDT significantly improved finger tapping score (p < 0.001) compared to the wait-list to the control group, whereas information processing speed did not significantly change (p = 0.673). The findings suggest that CDT is an effective conservative therapeutic approach to improve upper extremity fine motor function in women with BCRL. Future studies are needed to investigate the effect of CDT on different cognitive domains.

Screening Options in Autism Telediagnosis: Examination of TAP, M-CHAT-R, and DCI Concordance and Predictive Value in a Telediagnostic Model.

Tele-assessment of autism in early childhood has increased. However, it is unclear how autism screening tools (M-CHAT-R, DCI) function as part of tele-assessment and relate to a commonly used tele-assessment instrument, the TAP. 361 families from a clinically referred sample of children (mean age: 27.63 months, sd = 4.86 months) completed the M-CHAT-R and DCI prior to a tele-assessment visit utilizing the TAP. Data was collected on demographic background, measure scores, and diagnostic outcome. No significant differences in measure scores or diagnostic findings emerged in age at referral, age group, age at diagnosis, or child sex, ethnicity, or racial background. The M-CHAT-R and DCI correlated strongly and positively. Older age was associated with lower risk scores on screening instruments. Children with autism had significantly higher scores on all screener and subdomain scores, with the exception of DCI Behavior. Subdomains of the DCI emerged as the strongest predictor of diagnostic outcome. Both the DCI total score and the M-CHAT-R significantly related to diagnostic outcome and TAP score in this tele-assessment model, regardless of child age or sex. Findings also support use of the DCI for children under 24 months of age.

Development of 1,3a,6a-triazapentalene derivatives as practical erasable fluorescent cell staining reagents

1,3a,6a-Triazapentalene (TAP) derivatives were developed as erasable fluorescent cell staining reagents that can be used with a confocal laser microscope. To enhance the utility of previously developed erasable fluorescent cell staining reagents such as 2-biphenyl-TAP (1a) for practical applications in confocal laser microscopy, a carbonyl group with strong electron-withdrawing properties was introduced between the TAP core skeleton and the biphenyl group, leading to a longer wavelength shift in absorption and emission maxima. While the analog 1b, featuring only the carbonyl group insertion, declined significantly in fluorescence intensity, the two-carbon extended ketone analog 1d showed a desirable shift in absorption maximum towards longer wavelengths, green fluorescence, and high fluorescence intensity. Cell staining experiments using 1d demonstrated its usefulness, including rapid staining, erasable fluorescent staining, and compatibility with confocal laser microscopy employing a standard filter.

56 Predictors of Finger Tapping Variability in Older Adults Evaluated for a Neurodegenerative Memory Disorder

Objective:Patients with early Alzheimer Disease (AD) and Mild Cognitive Impairment of the Amnestic type (MCI-A) have been reported to show large variability of tapping scores. Factors that contribute to that variability remain undetermined. This preliminary study aimed to identify predictors of finger tapping variability in older adults evaluated for a neurodegenerative memory disorder. Based on earlier research with normally functioning adults, we predicted that the number of “invalid” tapping responses (i.e. failure of the index finger to adequately lift off the tapping key once it is depressed to produce the next number on a mechanical counter) and the female gender would predict finger tapping variability, but age and educational level would not predict variability.Participants and Methods:This preliminary study included 4 groups of participants, comprised of 8 healthy controls (HC, 3 males; 73±7years); 12 persons with subjective memory complaints (SMC, 3 males; 69±5 years); 12 with MCI-A (7 males; 76±5 years) and 7 early AD (5 males; 75±6years). All participants were administered a modified version of the Halstead Finger Tapping Test (HFTT). Mean, range of tapping score (i.e. a measure of variability), and number of invalid taps across 7 trials in each hand were calculated. ANOVA was performed for the HFTT metrics with the main effect of group. Tukey HSD tests were used for post hoc comparisons between groups. Multiple regression analysis was performed to determine the degree to which the number of invalid tapping responses, sex, age, and educational level predicted finger tapping variability using all 4 groups.Results:Mean tapping score did not vary significantly across groups in the dominant [F (3, 35) = 0.633, p = 0.599] or non-dominant [F (3, 35) = 2.345, p = 0.090] hand. Range score approached a significant difference between groups in the dominant hand [F (3, 35) = 2.745, p = 0.058], with a clear significant effect of group on range score in the non-dominant hand [F (3, 35) = 4.078, p = 0.014]. Range score in the nondominant hand was significantly higher in the AD compared to SMC (p = 0.018) and HC (p = 0.024). Regression analysis revealed statistically significant findings for the dominant hand (R2 = 0.327, F (4, 34) = 4.130, p = 0.008) and for the non-dominant hand (R2 = 0.330, F (4, 34) = 4.180, p = 0.007). For both the dominant and non-dominant hands, number of invalid taps significantly predicted range score (ß = 0.453, p = 0.044, and ß = 0.498, p = 0.012, respectively). Sex, age, and education years did not predict range scores.Conclusions:Variability of finger tapping in patients evaluated for neurodegenerative memory disorders and aged matched controls is predicted by the number of invalid tapping responses (comprising over 30% of the variance), but not by demographic variables in this clinical sample. Neurodegenerative disorders may eliminate a sex effect.

Mapping of the supplementary motor area using repetitive navigated transcranial magnetic stimulation.

The supplementary motor area (SMA) is important for motor and language function. Damage to the SMA may harm these functions, yet tools for a preoperative assessment of the area are still sparse. The aim of this study was to validate a mapping protocol using repetitive navigated transcranial magnetic stimulation (rnTMS) and extend this protocol for both hemispheres and lower extremities. To this purpose, the SMA of both hemispheres were mapped based on a finger tapping task for 30 healthy subjects (35.97 ± 15.11, range 21-67 years; 14 females) using rnTMS at 20 Hz (120% resting motor threshold (RMT)) while controlling for primary motor cortex activation. Points with induced errors were marked on the corresponding MRI. Next, on the identified SMA hotspot a bimanual finger tapping task and the Nine-Hole Peg Test (NHPT) were performed. Further, the lower extremity was mapped at 20 Hz (140%RMT) using a toe tapping task. Mean finger tapping scores decreased significantly during stimulation (25.70taps) compared to baseline (30.48; p < 0.01). Bimanual finger tapping led to a significant increase in taps during stimulation (28.43taps) compared to unimanual tapping (p < 0.01). Compared to baseline, completion time for the NHPT increased significantly during stimulation (baseline: 13.6 s, stimulation: 16.4 s; p < 0.01). No differences between hemispheres were observed. The current study validated and extended a rnTMS based protocol for the mapping of the SMA regarding motor function of upper and lower extremity. This protocol could be beneficial to better understand functional SMA organisation and improve preoperative planning in patients with SMA lesions.

A First Methodological Development and Validation of ReTap: An Open-Source UPDRS Finger Tapping Assessment Tool Based on Accelerometer-Data.

Bradykinesia is a cardinal hallmark of Parkinson's disease (PD). Improvement in bradykinesia is an important signature of effective treatment. Finger tapping is commonly used to index bradykinesia, albeit these approaches largely rely on subjective clinical evaluations. Moreover, recently developed automated bradykinesia scoring tools are proprietary and are not suitable for capturing intraday symptom fluctuation. We assessed finger tapping (i.e., Unified Parkinson's Disease Rating Scale (UPDRS) item 3.4) in 37 people with Parkinson's disease (PwP) during routine treatment follow ups and analyzed their 350 sessions of 10-s tapping using index finger accelerometry. Herein, we developed and validated ReTap, an open-source tool for the automated prediction of finger tapping scores. ReTap successfully detected tapping blocks in over 94% of cases and extracted clinically relevant kinematic features per tap. Importantly, based on the kinematic features, ReTap predicted expert-rated UPDRS scores significantly better than chance in a hold out validation sample (n = 102). Moreover, ReTap-predicted UPDRS scores correlated positively with expert ratings in over 70% of the individual subjects in the holdout dataset. ReTap has the potential to provide accessible and reliable finger tapping scores, either in the clinic or at home, and may contribute to open-source and detailed analyses of bradykinesia.

Autistic traits are associated with individual differences in finger tapping: an online study.

In a novel online study, we explored whether finger tapping differences are evident in people with autistic traits in the general population. We hypothesised that those with higher autistic traits would show more impairment in finger tapping, and that age would moderate tapping output. The study included a non-diagnosed population of 159 participants aged 18-78 who completed an online measure of autistic traits (the AQ-10) and a measure of finger tapping (the FTT). Results showed those with higher AQ-10 scores recorded lower tapping scores in both hands. Moderation analysis showed younger participants with more autistic traits recorded lower tapping scores for the dominant hand. This suggests motor differences seen in autism studies are evident in the general population.

Rationale 305: Phase 3 study of tislelizumab plus chemotherapy vs placebo plus chemotherapy as first-line treatment (1L) of advanced gastric or gastroesophageal junction adenocarcinoma (GC/GEJC).

286 Background: In a phase 2 study, tislelizumab (TIS), an anti-PD-1 monoclonal antibody, plus chemotherapy demonstrated durable antitumor activity as 1L in Chinese GC/GEJC patients (Xu et al, 2020). RATIONALE 305 (NCT03777657) was a global, double-blind, phase 3 study comparing 1L TIS plus investigator-chosen chemotherapy (TIS+ICC) vs placebo plus ICC (P+ICC) in GC/GEJC patients. Results from the interim analysis (IA) in the PD-L1+ population are presented; ITT population outcomes will be presented after final analysis. Methods: Adults with previously untreated, unresectable locally advanced or metastatic GC/GEJC, regardless of PD-L1 expression, were randomized (1:1) to receive TIS (200 mg IV Q3W) plus ICC (oxaliplatin [130 mg/m² IV Q3W] and oral capecitabine [1,000 mg/m² BID, Days 1-14 Q3W] or cisplatin [80 mg/m² IV Q3W] and 5-fluorouracil [800 mg/m²/day IV, Days 1-5 Q3W]) or P+ICC. Randomization was stratified by region, PD-L1 expression, peritoneal metastasis, and ICC. Patients with known HER2-positive status were excluded. RATIONALE 305 had dual primary endpoints of OS in the PD-L1+ and ITT analysis set; PD-L1+ was defined as PD-L1 TAP score ≥5% (VENTANA SP263 assay) assessed by blinded independent central laboratory. Secondary endpoints include PFS, ORR and DoR per RECIST 1.1, HRQoL, and safety profile. The prespecified IA was conducted after ~70% of total OS events had occurred. Results: Of 546 PD-L1+ patients enrolled from 13 counties/regions (73.8 % Asia; 26.2% Europe/ North America), 274 were randomized to receive TIS+ICC and 272 to receive P+ICC. As of 8 Oct 2021, median follow-up was 11.8 (TIS+ICC) and 11.7 mo (P+ICC). TIS+ICC showed statistically significant and clinically meaningful OS improvement vs P+ICC (HR 0.74 [95% CI: 0.59-0.94], mOS 17.2 vs 12.6 mo; 1-sided P= .0056). Compared with P+ICC, TIS+ICC also had longer PFS (mPFS 7.2 vs 5.9 mo; HR 0.67 [95% CI: 0.55-0.83]), higher ORR (50.4% vs 43.0%), and more durable response (mDoR 9.0 vs 7.1 mo). Patients treated with TIS+ICC reported better HRQoL than patients treated with P+ICC, as indicated by EORTC-QLQ-C30 global health status and physical functioning scores as well as the QLQST022 index score. No new safety signals were observed with TIS+ICC or P+ICC. While TEAEs leading to discontinuation of any treatment were higher with TIS+ICC than P+ICC (22.4% vs 12.1%), incidence rates of grade ≥3 TEAEs (64.7% vs 62.9%), serious TEAEs (42.3% vs 36.8%), and TEAEs leading to death (8.8% vs 7.7%) were comparable between both arms. Conclusions: In RATIONALE 305, TIS+ICC provided significant and clinically meaningful improvement in OS vs P+ICC with well acceptable safety as 1L in PD-L1+ patients with advanced GC/GEJC. These data suggest this combination is a new 1L option for this patient population. Clinical trial information: NCT03777657 .

Identification of potential CD8+ epitopes in pp62 polyprotein of African swine fever virus using computational immunology.

The highly infectious African swine fever virus (ASFV) is currently the only known DNA arbovirus within the Asfarviridae family which primarily infects domestic pigs and wild boars. African swine fever (ASF) leads to a mortality rate of up to 100% which has caused massive socio-economic losses worldwide. Previous research indicates that ASFV's virulence can be attributed to polyprotein pp62, which plays a crucial role in viral assembly and core maturation. This particular study utilized in silico analysis to identify highly conserved cytotoxic T-cell epitopes in pp62 that can potentially serve as key components for future ASFV vaccines. To achieve this, the researchers retrieved, clustered, and aligned the peptide sequences of pp62. Subsequently, the aligned sequences were analyzed to identify epitopes that bind promiscuously to the swine major histocompatibility complex I (MHC I) alleles and exhibiting MHC IC50 values < 500 nM. Additionally, peptide sequences with positive proteasome and TAP scores were considered. Potential cross-reactivity was assessed by comparing the peptide sequences against available proteome sequences of Sus scrofa domesticus in various databases. Furthermore, molecular docking was conducted to evaluate the binding of candidate epitopes with swine leukocyte antigen-1*0401 (SLA-1*0401). The dissociation constants, binding energies, root mean square deviation, and root mean square fluctuation values for the SLA-epitope complexes were compared with a positive reference. In the course of the study, 21 highly conserved CD8+ epitopes were identified, out of which four were further assessed for their potential immunogenicity. The results demonstrated that the highly conserved CD8+ epitopes discovered in this study are promising for integration into future ASFV vaccine formulations. As preliminary data, it is anticipated that these findings will subsequently undergo in vitro and in vivo studies in the future.

Tele-assessment of young children referred for autism spectrum disorder evaluation during COVID-19: Associations among clinical characteristics and diagnostic outcome.

The diagnosis of autism spectrum disorder (ASD) has traditionally been made through in-person evaluation. While the COVID-19 pandemic disrupted access to ASD services, there has been remarkable growth in research focused on novel ASD diagnostic practices, including the use of telemedicine. We implemented a standard ASD tele-assessment evaluation procedure, including use of a novel remote clinician-coached, caregiver-delivered ASD assessment tool (TELE-ASD-PEDS; TAP), with the goal of continuing to provide diagnostic services to young children and their families during the pandemic. We examined the relationship between child characteristics and diagnostic outcome for 335 children, ages 14-78 months, who received ASD tele-assessment conducted by psychologists and pediatricians in an outpatient clinic of a Midwestern academic medical center. We found that clinicians could make a determination about ASD diagnosis for most children (85%) evaluated using tele-assessment. Child clinical characteristics, including TAP scores and clinician ratings of ASD symptoms, were related to diagnostic outcome (i.e. diagnosis of ASD, no ASD, and Unsure about ASD). When all clinical characteristics were examined together, the presence of specific repetitive behaviors predicted ASD diagnosis. We also found that the TAP is effective for making an ASD diagnosis when used as part of comprehensive tele-assessment evaluation in children ⩾ 36 months of age with delayed language. Our study adds to an increasing body of research supporting use of tele-assessment for diagnosis of ASD. Although further research is needed, telemedicine may help families from different backgrounds and geographic locations to access high-quality diagnostic services.

Low-intensity transcranial ultrasound stimulation facilitates hand motor function and cortical excitability: A crossover, randomized, double blind study.

ObjectiveTranscranial ultrasound stimulation (TUS) is a new form of non-invasive brain stimulation. Low-intensity TUS is considered highly safe. We aimed to investigate the effect of low-intensity TUS on hand reaction responses and cortical excitability in healthy adults.MethodsThis study used a crossover, randomized, and double-blind design. A total of 20 healthy participants were recruited for the study. All the participants received TUS and sham stimulation on separate days in random order. The finger tapping test (tapping score by using a tablet) and motor evoked potential (MEP) were assessed before and after stimulation, and discomfort levels were assessed using a visual analog scale (VAS) score.ResultsNo significant differences in tapping score or MEP amplitude between the two experimental conditions were registered before stimulation. After stimulation, tapping scores were increased regardless of the specific treatment, and the real stimulation condition receiving TUS (90.4 ± 11.0 points) outperformed the sham stimulation condition (86.1 ± 8.4 points) (p = 0.002). The MEP latency of real TUS (21.85 ± 1.33 ms) was shorter than that of sham TUS (22.42 ± 1.43 ms) (p < 0.001). MEP amplitude of real TUS (132.18 ± 23.28 μV) was higher than that of sham TUS (114.74 ± 25.5 μV, p = 0.005). There was no significant difference in the discomfort score between the two conditions (p = 0.163).ConclusionTranscranial ultrasound stimulation (TUS) can decrease the hand reaction response time and latency of the MEP, enhance the excitability of the motor cortex, and improve hand motor function in healthy individuals without obvious discomfort.

Effects of auricular acupuncture stimulation on healthy adults' upper limb motor-evoked potentials: A randomized, crossover, double-blind study.

The aim of this study was to determine whether auricular acupuncture has neuromodulatory effects on the motor cortex of healthy adults. Fourteen healthy subjects received a real auricular acupuncture stimulation (SF1) session and a sham acupuncture stimulation session. The interval between the two types of stimulation was more than 24 h. A finger dexterity test (taping score and taping speed by using ipad) was assessed, and motor-evoked potentials (MEP) were assessed before and after each stimulation. Before the treatment, there were no significant differences in MEP amplitude, tapping score, or tapping speed (P > 0.05) between the real and sham stimulation conditions. After the treatment, the MEP amplitude, tapping score, and tapping speed in the real stimulation condition increased significantly compared to the pre-stimulation measurements and were significantly higher than those in the sham stimulation condition (P < 0.01). In the sham stimulation condition, the MEP amplitude, tapping score, and tapping speed decreased significantly compared to the pre-stimulation measurements (P < 0.05). Acupuncture of auricular points can modulate the excitability of the motor cortex area of controlling the upper limbs. [http://www.chictr.org.cn/index.aspx], identifier [ChiCTR2100051608].

Set to fail: Affective dynamics in a resistance training program designed to reach muscle concentric failure.

Grounded in hedonic assumptions, evidence suggests that people tend to engage in activities they consider pleasurable and enjoyable, while trying to avoid pain and displeasure. This suggests that the dynamic between positive and negative affect can influence current behavior and the intentions to continue performing. Regarding resistance training (RT), research focusing on how to promote a better affective response is still scarce and much needed. Given existing limitations and theoretical suggestions, a RT program was developed and applied to recreational exercisers in a quasi-experimental design aiming to (1) explore the affective response dynamic through an assessment after the last set of each exercise; and (2) analyze possible differences of preference and tolerance profiles in affective variables (core affect and enjoyment). For that purpose, 43 participants (21 male and 22 female; Mage =34.69 ± 6.71 years; Mexperience =8.32 ± 4.54 years; MBMI =24.26 ± 2.64 kg/m2 ) accepted to participate in this study. Descriptive statistics, correlational, and group comparisons analyses were performed to provide evidence for proposed objectives. The present study showed that measures of affective valence/arousal applied immediately after a set represents a feasible and ecologically valid approach to tap core affect. Results presented evidence that recreationally trained exercisers in a common RT program would need a minimum of one measurement to assess the affective response. However, additional assessments could refine the understanding of exercise pleasurable experience. Results also suggest that exercisers with distinct profiles of preference/tolerance depicted differentiated patterns for the affective response, possibly justifying a distinct approach when promoting affective regulation.

Randomized, phase 3 study of second-line tislelizumab vs chemotherapy in advanced or metastatic esophageal squamous cell carcinoma, RATIONALE 302: Asia subgroup.

e16107 Background: In the global Phase 3 study RATIONALE 302 (NCT03430843), tislelizumab (TIS) demonstrated statistically and clinically significant improvement in overall survival (OS) vs chemotherapy (chemo) (median OS 8.6 vs 6.3 months; HR 0.70; 95% CI 0.57, 0.85; p=0.0001) in patients with advanced or metastatic ESCC. Here, we report data from the Asia subgroup. Methods: Eligible patients who had disease progression after first-line systemic therapy were randomized 1:1 to receive TIS 200 mg intravenously once every three weeks or chemo (paclitaxel, docetaxel, or irinotecan) until disease progression, intolerable toxicity, or withdrawal. The primary endpoint was OS in all randomized patients (intent-to-treat population). The key secondary endpoint was OS in patients with PD-L1 Tumor Area Positivity Score* ≥ 10%; other secondary endpoints included progression-free survival (PFS), objective response rate (ORR), duration of response (DoR), health-related quality of life, and safety. Results: Of the 512 randomized patients, 404 (79%) were enrolled from China, Taiwan, Japan, and Korea and constituted the Asia subgroup (n=201 TIS, n=203 chemo). At data cut-off (December 1, 2020), median follow-up was 6.9 months in the Asia subgroup. Median OS was 8.5 months with TIS vs 6.3 months with chemo (HR 0.73; 95% CI 0.59, 0.90). Median PFS was 1.5 months with TIS vs 1.7 months with chemo (HR 0.81; 95% CI 0.64, 1.02). TIS resulted in a higher ORR (20.4% [95% CI 15.1, 26.6] vs 9.4% [95% CI 5.7, 14.2]) and longer median DoR (7.4 vs 4.0 months; HR 0.42; 95% CI 0.21, 0.84) vs chemo. In the safety analysis set (n=201 TIS, n=191 chemo), patients treated with TIS had fewer treatment-related adverse events (TRAEs) (74.1% vs 95.3%), fewer ≥ Grade 3 TRAEs (19.4% vs 57.1%), fewer serious TRAEs (15.4% vs 20.9%), and a similar incidence of TRAEs leading to death (2.5% vs 2.6%) vs chemo. Conclusions: In the Asia subgroup, TIS improved OS and tumor response vs chemo as second-line treatment in patients with advanced or metastatic ESCC and showed a well-tolerated safety profile. These findings were consistent with published results in the overall population. *The TAP score methodology has been previously referred to as visually-estimated combined positive score (vCPS) and was previously presented at the American Society of Clinical Oncology 2021, June 4–8, 2021, ESMO World Gastrointestinal Congress 2021, June 30–July 3, 2021, and The Chinese Society of Clinical Oncology 2021, September 25–29, 2021. Clinical trial information: NCT03430843.

A Simple Field Tapping Test for Evaluating Frequency Qualities of the Lower Limb Neuromuscular System in Soccer Players: A Validity and Reliability Study.

Over the years, the foot tapping test protocol has been proposed by scientists to identify the capabilities of the lower limb neuromuscular system in the medical context; however, to our knowledge, no studies have established its usefulness and relationship to athletic performance. The aim of the present study was to test the reliability, criterion validity and sensitivity of a new foot tapping (TAP) test, and to examine its relationship with proxies of athletic performance in soccer players. Forty voluntary soccer players of two different levels participated in this study (20 players from the national level: age: 22.6 ± 2.5 years and 20 players from regional level: 25.1 ± 3.6 years). They performed the TAP test on two separate occasions to test its relative and absolute reliability. To examine the criterion validity of the TAP test, all participants performed four types of jumps, sprint tests, agility tests, the Wingate test and the finger tapping test considered a gold standard tapping test. The sensitivity was assessed with national and regional player levels. The TAP test presented a high relative and absolute reliability with intra-class correlation coefficient ICC > 0.90, standard errors of measurement SEM < 5% and mean difference ±95% limits of agreement equal to 0.2 ± 0.8 tap·s−1. National level players showed a higher TAP score (p < 0.001; dz = 1.96, large) compared to regional players (9.68 ± 1.41 tap·s−1 vs. 7.28 ± 1.01 tap·s−1, respectively) and the value of area under curve measured by the receiver operating characteristic curve technique was 0.95 (95% CI: 0.827–0.990). The TAP test showed a significant association with the finger tapping test (r = 0.84, p < 0.001), whereas no correlation was seen between the TAP test and all the other physical tests measured. The TAP test could be considered a valid and reliable test to assess lower limb neuromuscular ability in soccer players.

Randomized, phase 3 study of second-line tislelizumab versus chemotherapy in advanced or metastatic esophageal squamous cell carcinoma, RATIONALE 302: Asia subgroup.

279 Background: In the global Phase 3 study RATIONALE 302 (NCT03430843), tislelizumab (TIS) demonstrated statistically and clinically significant improvement in overall survival (OS) vs chemotherapy (chemo) (median OS 8.6 vs 6.3 months; HR 0.70, 95% CI 0.57–0.85; p=0.0001) in patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC). Here, we report data from the Asia subgroup. Methods: Eligible patients who had disease progression after first-line systemic therapy were randomized 1:1 to receive TIS 200 mg intravenously once every three weeks or chemo (paclitaxel, docetaxel, or irinotecan) until disease progression, intolerable toxicity, or withdrawal. The primary endpoint was OS in all randomized patients (Intent-to-treat population). The key secondary endpoint was OS in patients with PD-L1 Tumor Area Positivity Score* ≥ 10%; other secondary endpoints included progression-free survival (PFS), objective response rate (ORR), duration of response (DoR), health-related quality of life, and safety. Results: Of the 512 randomized patients, 404 (79%) were enrolled from China, Taiwan, Japan, and Korea and constituted the Asia subgroup (n=201 TIS, n=203 chemo). At data cut-off (December 1, 2020), median follow-up was 6.9 months in the Asia subgroup. Median OS was 8.5 months with TIS vs 6.3 months with chemo (HR 0.73; 95% CI 0.59, 0.90). Median PFS was 1.5 months with TIS vs 1.7 months with chemo (HR 0.81; 95% CI 0.64, 1.02). TIS resulted in a higher ORR (20.4% [95% CI 15.1, 26.6] vs 9.4% [95% CI 5.7, 14.2]) and longer median DoR (7.4 vs 4.0 months; HR 0.42, 95% CI 0.21, 0.84) vs chemo. In the safety analysis set (n=201 TIS, n=191 chemo), patients treated with TIS had fewer treatment-related adverse events (TRAEs) (74.1% vs 95.3%), fewer ≥ Grade 3 TRAEs (19.4% vs 57.1%), fewer serious TRAEs (15.4% vs 20.9%), and a similar incidence of TRAEs leading to death (2.5% vs 2.6%) vs chemo. Conclusions: In the Asia subgroup, TIS improved OS and tumor response vs chemo as second-line treatment in patients with advanced or metastatic ESCC and showed a well-tolerated safety profile. These findings were consistent with published results in the overall population. *The TAP score methodology has been previously referred to as visually-estimated combined positive score (vCPS) and was previously presented at the American Society of Clinical Oncology 2021, June 4–8, 2021, ESMO World Gastrointestinal Congress 2021, June 30–July 3, 2021, and The Chinese Society of Clinical Oncology 2021, September 25–29, 2021. Clinical trial information: NCT03430843.

Indices of callosal axonal density and radius from diffusion MRI relate to upper and lower limb motor performance

Understanding the relationship between human brain structure and functional outcome is of critical importance in systems neuroscience. Diffusion MRI (dMRI) studies show that fractional anisotropy (FA) is predictive of motor control, underscoring the importance of white matter (WM). However, as FA is a surrogate marker of WM, we aim to shed new light on the structural underpinnings of this relationship by applying a multi-compartment microstructure model providing axonal density/radius indices. Sixteen young adults (7 males / 9 females), performed a hand/foot tapping task and a Multi Limb Reaction Time task. Furthermore, diffusion (STEAM &HARDI) and fMRI (localizer hand/foot activations) data were obtained. Sphere ROIs were placed on activation clusters with highest t value to guide interhemispheric WM tractography. Axonal radius/density indices of callosal parts intersecting with tractography were calculated from STEAM, using the diffusion-time dependent AxCaliber model, and correlated with behavior. Results indicated a possible association between larger apparent axonal radii of callosal motor fibers of the hand and higher tapping scores of both hands, and faster selection-related processing (normalized reaction) times (RTs) on diagonal limb combinations. Additionally, a trend was present for faster selection-related processing (normalized reaction) times for lower limbs being related with higher axonal density of callosal foot motor fibers, and for higher FA values of callosal motor fibers in general being related with better tapping and faster selection-related processing (normalized reaction) times. Whereas FA is sensitive in demonstrating associations with motor behavior, axon radius/density (i.e., fiber geometry) measures are promising to explain the physiological source behind the observed FA changes, contributing to deeper insights into brain-behavior interactions.

Quantifying Parkinson’s disease motor severity under uncertainty using MDS-UPDRS videos

Parkinson’s disease (PD) is a brain disorder that primarily affects motor function, leading to slow movement, tremor, and stiffness, as well as postural instability and difficulty with walking/balance. The severity of PD motor impairments is clinically assessed by part III of the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), a universally-accepted rating scale. However, experts often disagree on the exact scoring of individuals. In the presence of label noise, training a machine learning model using only scores from a single rater may introduce bias, while training models with multiple noisy ratings is a challenging task due to the inter-rater variabilities. In this paper, we introduce an ordinal focal neural network to estimate the MDS-UPDRS scores from input videos, to leverage the ordinal nature of MDS-UPDRS scores and combat class imbalance. To handle multiple noisy labels per exam, the training of the network is regularized via rater confusion estimation (RCE), which encodes the rating habits and skills of raters via a confusion matrix. We apply our pipeline to estimate MDS-UPDRS test scores from their video recordings including gait (with multiple Raters, R=3) and finger tapping scores (single rater). On a sizable clinical dataset for the gait test (N=55), we obtained a classification accuracy of 72% with majority vote as ground-truth, and an accuracy of ∼84% of our model predicting at least one of the raters’ scores. Our work demonstrates how computer-assisted technologies can be used to track patients and their motor impairments, even when there is uncertainty in the clinical ratings. The latest version of the code will be available at https://github.com/mlu355/PD-Motor-Severity-Estimation.

GEORGE®: A Pilot Study of a Smartphone Application for Huntington's Disease.

Current Huntington's disease (HD) measures are limited to subjective, episodic assessments conducted in clinic. Smartphones can enable the collection of objective, real-world data but their use has not been extensively evaluated in HD. Develop and evaluate a smartphone application to assess feasibility of use and key features of HD in clinic and at home. We developed GEORGE®, an Android smartphone application for HD which assesses voice, chorea, balance, gait, and finger tapping speed. We then conducted an observational pilot study of individuals with manifest HD, prodromal HD, and without a movement disorder. In clinic, participants performed standard clinical assessments and a battery of active tasks in GEORGE. At home, participants were instructed to complete the activities thrice daily for one month. Sensor data were used to measure chorea, tap rate, and step count. Audio data was not analyzed. Twenty-three participants (8 manifest HD, 5 prodromal HD, 10 controls) enrolled, and all but one completed the study. On average, participants used the application 2.1 times daily. We observed a significant difference in chorea score (HD: 19.5; prodromal HD: 4.5, p = 0.007; controls: 4.3, p = 0.001) and tap rate (HD: 2.5 taps/s; prodromal HD: 8.9 taps/s, p = 0.001; controls: 8.1 taps/s, p = 0.001) between individuals with and without manifest HD. Tap rate correlated strongly with the traditional UHDRS finger tapping score (left hand: r = -0.82, p = 0.022; right hand: r = -0.79, p = 0.03). GEORGE is an acceptable and effective tool to differentiate individuals with and without manifest HD and measure key disease features. Refinement of the application's interface and activities will improve its usability and sensitivity and, ideally, make it useful for clinical care and research.

All-cause Dementia Prediction by Machine Learning: The Health, Aging, and Body Composition Study

There are several shortcomings of the currently available risk prediction models for dementia. We developed a risk prediction model for dementia using machine-learning approach and compared its performance with traditional approaches. Data were from the Health, Aging, and Body Composition Study, comprising 3,075 older adults (at least 70 years). Dementia was defined as (1) use of a prescribed dementia medication, (2) adjudicated dementia diagnosis, or (3) a race-stratified cognitive decline>1.5 SDs from the baseline mean. We selected 275 predictors collected from questionnaires, imaging data, performance testing, and biospecimen. We used random survival forest (RSF) to build the full model and rank the importance of predictors. Subsequently, we built parsimonious models with top-20 predictors using RSF and Cox regression. A dementia risk score was developed using top-ranked variables. We used the C-statistic for performance evaluation. Over a median of 11.4 years of follow-up, 659 dementias (21.4%) occurred. The RSF model (both including all and top-20 variables) showed a higher C-statistic than the regression model. Digit symbol score, physical performance battery, finger tapping score, weight change since age 50, serum adiponectin, and APOE genotype were the top-6 variables. We created a dementia risk score (0-10) using the top-6 variables. A 1-unit increase in the risk score was associated with an 8% higher risk of dementia. The risk score demonstrated good discrimination (C-statistic=0.75). Machine learning methods offered improvement over traditional approaches in predicting dementia. The risk prediction score derived from a parsimonious model had good prediction performance.