Temporal Coherence Shapes Cortical Responses to Speech Mixtures in a Ferret Cocktail Party.

Segregation of complex sounds such as speech, music and animal vocalizations as they simultaneously emanate from multiple sources (referred to as the "cocktail party problem") is a remarkable ability that is common in humans and animals alike. The neural underpinnings of this process have been extensively studied behaviorally and physiologically in non-human animals primarily with simplified sounds (tones and noise sequences). In humans, segregation experiments utilizing more complex speech mixtures are common; but physiological experiments have relied on EEG/MEG/ECoG recordings that sample activity from thousands of neurons, often obscuring the detailed processes that give rise to the observed segregation. The present study combines the insights from animal single-unit physiology with segregation of speech-like mixtures. Ferrets were trained to attend to a female voice and detect a target word, both in presence or absence of a concurrent, equally salient male voice. Single neuron recordings were obtained from primary and secondary ferret auditory cortical fields, as well as frontal cortex. During task performance, representation of the female words became more enhanced relative to those of the (distractor) male in all cortical regions, especially in the higher auditory cortical field. Analysis of the temporal and spectral response characteristics during task performance reveals how speech segregation gradually emerges in the auditory cortex. A computational model evaluated on the same voice mixtures replicates and extends these results to different attentional targets (attention to female or male voices). These findings are consistent with the temporal coherence theory whereby attention to a target voice anchors neural activity in cortical networks hence binding together channels that are coherently temporally-modulated with the target, and ultimately forming a common auditory stream.

Between Technological Utopia and Dystopia: Online Expression of Compulsory Use of Surveillance Technology.

This study investigated people's ethical concerns of surveillance technology. By adopting the spectrum of technological utopian and dystopian narratives, how people perceive a society constructed through the compulsory use of surveillance technology was explored. This study empirically examined the anonymous online expression of attitudes toward the society-wide, compulsory adoption of a contact tracing app that affected almost every aspect of all people's everyday lives at a societal level. By applying the structural topic modeling approach to analyze comments on four Hong Kong anonymous discussion forums, topics concerning the technological utopian, dystopian, and pragmatic views on the surveillance app were discovered. The findings showed that people with a technological utopian view on this app believed that the implementation of compulsory app use can facilitate social good and maintain social order. In contrast, individuals who had a technological dystopian view expressed privacy concerns and distrust of this surveillance technology. Techno-pragmatists took a balanced approach and evaluated its implementation practically.

Shaping DNA damage responses: Therapeutic potential of targeting telomeric proteins and DNA repair factors in cancer.

Shelterin proteins regulate genomic stability by preventing inappropriate DNA damage responses (DDRs) at telomeres. Unprotected telomeres lead to persistent DDR causing cell cycle inhibition, growth arrest, and apoptosis. Cancer cells rely on DDR to protect themselves from DNA lesions and exogenous DNA-damaging agents such as chemotherapy and radiotherapy. Therefore, targeting DDR machinery is a promising strategy to increase the sensitivity of cancer cells to existing cancer therapies. However, the success of these DDR inhibitors depends on other mutations, and over time, patients develop resistance to these therapies. This suggests the need for alternative approaches. One promising strategy is co-inhibiting shelterin proteins with DDR molecules, which would offset cellular fitness in DNA repair in a mutation-independent manner. This review highlights the associations and dependencies of the shelterin complex with the DDR proteins and discusses potential co-inhibition strategies that might improve the therapeutic potential of current inhibitors.

The measurement properties and feasibility of FRAIL scale in older adults: A systematic review and meta-analysis.

Frailty is a prevalent condition amongst older adults, significantly affecting their quality of life. The FRAIL tool has been purposefully designed for clinical application by assisting healthcare professionals in identifying and managing frailty-related issues in older adults, making it a preferred choice for assessing frailty across diverse older populations. This review aimed to synthesize the measurement properties and feasibility of FRAIL. Guided by COSMIN guidelines, seven databases were searched from inception to 31 Mar 2023. The measurement properties were extracted for quality appraisal of the populations in the studied samples. Where possible, random-effects meta-analysis and meta-regression were used for quantitative synthesis. Eighteen articles containing 273 tests were drawn from 14 different populations. We found that populations testing for criterion validity had high-quality ratings, while construct validity ratings varied based on health status and geographical region. Test-retest reliability had sufficient quality ratings, while scale agreement had sufficient ratings in only four out of 14 populations tested. Responsiveness ratings were insufficient in seven out of eight populations, with inconsistent ratings in one population. Our analysis of missing data across three articles showed a 16.3% rate, indicating good feasibility of the FRAIL. FRAIL is a feasible tool for assessing frailty of older adults in community settings, with good criterion validity and test-retest reliability. However, more research is needed on construct validity and responsiveness.

Efficacy and tolerability of adjunctive lacosamide in patients aged <4 years with focal seizures.

OBJECTIVE: Primary objective was to evaluate efficacy of lacosamide administered concomitantly with 1-3 antiseizure medications in young children with uncontrolled focal (partial-onset) seizures. METHODS: Double-blind, parallel-group trial (SP0967: NCT02477839/2013-000717-20) conducted between June 2015 and May 2020 at hospitals and clinics in 25 countries. Patients (aged ≥1 month to <4 years) with uncontrolled focal seizures were randomized 1:1 to adjunctive lacosamide or placebo using an interactive voice/web response system and stratified by age. After a 20-day titration period, patients who reached target-dose range (8-12 mg/kg/day) entered a 7-day maintenance period. Region-specific primary efficacy variables were based on ≤72-h video-electroencephalograms: change in average daily frequency (ADF) of electrographic focal seizures as measured on end-of-maintenance video-electroencephalogram versus end-of-baseline video-electroencephalogram (United States); 50% responder rate (≥50% reduction in ADF of focal seizures) during maintenance (European Union). RESULTS: In total, 255 patients were randomized (lacosamide/placebo: 128/127) and received ≥1 trial medication dose. Percentage reduction in ADF of focal seizures for lacosamide (116 patients) versus placebo (120 patients) was 3.2% (95% confidence interval = -13.6 to 17.5, p = 0.69). 50% responder rate was 41.4% for lacosamide (116 patients), 37.5% for placebo (120 patients) (p = 0.58). Treatment-emergent adverse events were reported by 44.5% of lacosamide-treated patients (placebo 51.2%). INTERPRETATION: Adjunctive lacosamide did not show superior efficacy versus placebo in young children with focal seizures. However, efficacy variables were potentially affected by high variability and low reliability between readers in video-electroencephalogram interpretation. Lacosamide was generally well tolerated; safety profile was acceptable and consistent with that in adults and children aged ≥4 years.

Seeing through a robot's eyes: A cross-sectional exploratory study in developing a robotic screening technology for autism.

The present exploratory cross-sectional case-control study sought to develop a reliable and scalable screening tool for autism using a social robot. The robot HUMANE, installed with computer vision and linked with recognition technology, detected the direction of eye gaze of children. Children aged 3-8 (M = 5.52; N = 199) participated, 87 of whom had been confirmed with autism, 55 of whom were suspected to have autism, and 57 of whom were not considered to cause any concern for having autism. Before a session, a human experimenter instructed HUMANE to narrate a story to a child. HUMANE prompted the child to return his/her eye gaze to the robot if the child looked away, and praised the child when it re-established its eye gaze quickly after a prompt. The reliability of eye gaze detection was checked across all pairs of human raters and HUMANE and reached 0.90, indicating excellent interrater agreement. Using the pre-specified reference standard (Autism Spectrum Quotient), the sensitivity and specificity of the index tests (i.e., the number of robot prompts and duration of inattentiveness) reached 0.88 or above and the Diagnostic Odds Ratios were beyond 190. These results show that social robots may detect atypical eye patterns, suggesting a potential future for screening autism using social robots.

Asymmetric Dimethylarginine Enables Depolarizing Spikes and Vasospasm in Mesenteric and Coronary Resistance Arteries.

BACKGROUND: Increased vasoreactivity due to reduced endothelial NO bioavailability is an underlying feature of cardiovascular disease, including hypertension. In small resistance arteries, declining NO enhances vascular smooth muscle (VSM) reactivity partly by enabling rapid depolarizing Ca2+-based spikes that underlie vasospasm. The endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA) is metabolized by DDAH1 (dimethylarginine dimethylaminohydrolase 1) and elevated in cardiovascular disease. We hypothesized ADMA might enable VSM spikes and vasospasm by reducing NO bioavailability, which is opposed by DDAH1 activity and L-arginine. METHODS: Rat isolated small mesenteric arteries and myogenic rat-isolated intraseptal coronary arteries (RCA) were studied using myography, VSM intracellular recording, Ca2+ imaging, and DDAH1 immunolabeling. Exogenous ADMA was used to inhibit NO synthase and a selective DDAH1 inhibitor, NG-(2-methoxyethyl) arginine, to assess the functional impact of ADMA metabolism. RESULTS: ADMA enhanced rat-isolated small mesenteric arteries vasoreactivity to the α1-adrenoceptor agonist, phenylephrine by enabling T-type voltage-gated calcium channel-dependent depolarizing spikes. However, some endothelium-dependent NO-vasorelaxation remained, which was sensitive to DDAH1-inhibition with NG-(2-methoxyethyl) arginine. In myogenically active RCA, ADMA alone stimulated depolarizing Ca2+ spikes and marked vasoconstriction, while NO vasorelaxation was abolished. DDAH1 expression was greater in rat-isolated small mesenteric arteries endothelium compared with RCA, but low in VSM of both arteries. L-arginine prevented depolarizing spikes and protected NO-vasorelaxation in rat-isolated small mesenteric artery and RCA. CONCLUSIONS: ADMA increases VSM electrical excitability enhancing vasoreactivity. Endothelial DDAH1 reduces this effect, and low levels of DDAH1 in RCAs may render them susceptible to endothelial dysfunction contributing to vasospasm, changes opposed by L-arginine.

Burgers, Fast Foods, and Increased Associated Risk for Atopic Dermatitis: A Cross-Sectional Study of Dietary Habits among Young Chinese Adults in Singapore/Malaysia.

BACKGROUND: We see increasing evidence that dietary and nutrients factors play a pivotal role in allergic diseases and recent global findings suggest that dietary habits influence the pathogenesis of atopic dermatitis (AD). Frequent consumption of fast food diets is associated with AD development. Despite the rising prevalence of AD in Asia, efforts in investigating the role of dietary habits and AD in adults are still lacking. METHODS: We evaluated the association between the dietary intake of 16 food types and AD manifestations using our Singapore/Malaysia Cross-sectional Genetics Epidemiology Study (SMCGES) population. Dietary habits profiles of 11,494 young Chinese adults (1,550 AD cases/2,978 non-atopic controls/6,386 atopic controls) were assessed by an investigator-administered questionnaire. AD cases were further evaluated for their chronicity (550 chronic) and severity (628 moderate-to-severe). Additionally, we derived a novel food index, Quality of Diet based on Glycaemic Index Score (QDGIS), to examine the association between dietary intake of glycaemic index (GI) and various AD phenotypes. RESULTS: The majority of AD subjects are distributed in the good (37.1%) and moderate (36.2%) QDGIS classes. From the multivariable analyses for age and gender, a moderate QDGIS class was significantly associated with a lower odds of AD (adjusted odds ratio (AOR): 0.844; 95% confidence interval (CI): 0.719-0.991; p < 0.05) and moderate-to-severe AD (AOR: 0.839; 95% CI: 0.714-0.985; p < 0.05). A good QDGIS class was only significantly associated with a lower odds of chronic AD (AOR: 0.769; 95% CI: 0.606-0.976; p < 0.05). Among high GI foods, frequent consumption of burgers/fast food was strongly associated with an increased risk of chronic and moderate-to-severe AD. Among low GI foods, increased intake frequencies of fruits, vegetables, and pulses decreased the odds of AD. Finally, we identified significant associations between frequent seafood, margarine, butter, and pasta consumption with an increased odds of AD despite them having little GI values. CONCLUSION: While genetic components are well-established in their risks associated with increased AD prevalence, there is still a lack of a focus epidemiology study associating dietary influence with AD. Based on the first allergic epidemiology study conducted here in Singapore and Malaysia, it laid the groundwork to guide potential dietary interventions from changing personal dietary habits.

Effectiveness of anthocyanin-rich foods on bone remodeling biomarkers of middle-aged and older adults at risk of osteoporosis: a systematic review, meta-analysis, and meta-regression.

CONTEXT: Current osteoporosis pharmacological treatment has undesirable side effects. There is increasing focus on naturally derived food substances that contain phytonutrients with antioxidant effects in promoting health and regulating immune response. OBJECTIVE: This review aims to systematically evaluate the effectiveness of anthocyanin-rich foods on bone remodeling biomarkers in middle-aged and older adults (≥40 y old) at risk of osteoporosis. DATA SOURCES: Randomized controlled trials were searched on 8 bibliographic databases of PubMed, Embase, Scopus, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Food Science and Technology Abstracts, Cochrane Library, and ProQuest. DATA EXTRACTION AND ANALYSIS: Thirteen studies were included in the meta-analysis. Receptor activator of nuclear factor kappa-B ligand (RANKL) is exhibited from osteoblastic cells that gathered osteoclasts to bone sites for bone resorption, accelerating bone loss. Anthocyanin-rich food consumption showed statistically nonsignificant effects, with no substantial heterogeneity on bone remodeling biomarkers. However, there was a significant increase in lumbar spine L1-L4 bone mineral density. Mild-to-small effects were seen to largely favor the consumption of anthocyanin-rich foods. Berries (d = -0.44) have a larger effect size of RANKL than plums (d = 0.18), with statistically significant subgroup differences. Random-effects meta-regression found body mass index, total attrition rate, total energy, and dietary carbohydrate and fat intake were significant covariates for the effect size of RANKL. All outcomes had low certainty of evidence. CONCLUSION: Anthocyanin-rich foods may improve bone health in middle-aged and older adults at risk of osteoporosis. This review contributes to the growing interest in nutrient-rich foods as a low-cost and modifiable alternative to promote human health and reduce disease burden. Future high-quality studies with larger sample sizes and longer treatment durations are required to fully understand the effect of anthocyanin-rich foods on bone health. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42022367136.

Refractory Jeavons Syndrome from Birth Symptomatic to PLCB1 Mutation.

Jeavons syndrome is a common, often misdiagnosed or overlooked epileptic syndrome presenting with a triad of eyelid myoclonia with or without absence seizures, eye closure-induced EEG paroxysms, and photosensitivity. We present a seven-year-old female who presented with eyelid myoclonia evident since birth with absence seizures and migraines with associated photosensitivity. An EEG with photic stimulation confirmed the diagnosis of Jeavons syndrome. Genetic testing showed a heterozygous mutation in the PLCB1 gene which has been linked to early onset epilepsies and encephalopathic epilepsies. This mutation and her clinical presentation identifies another etiology of Jeavons syndrome and confirms it can begin from birth. Its presence highlights the importance of genetic testing in epileptic patients to better understand the links between genetics and epilepsy syndromes so appropriate treatment can be initiated.

T cells with split CARs specific for NKG2D ligands and PD-L1 exhibit improved selectivity towards monocyte-derived cells while effective in eliminating acute myeloid leukaemia in vivo.

PURPOSE: The expression of NKG2D ligands and PD-L1 has been detected on acute myeloid leukaemia (AML) cells, as well as normal cells of the myeloid lineage. To target leukemic cells while minimizing collateral damage to normal cells, we constructed a split dual CAR system based on the AND-gate logic. METHODS: The NKG2D extracellular domain linked with DAP12 without a co-stimulatory signal was used for the basal activation of T cells, and used together with the PD-L1-specific chimeric costimulatory receptor containing the 4-1BB activating domain for co-stimulatory signal 2 input. This dual CAR displayed cell-type specificity and activity similar as a 2nd generation NKG2D ligand-specific CAR. RESULTS: When compared to CD64 and PD-L1-specific 2nd generation CARs, we observed that the split dual CAR offered an improved myeloid cell type selectivity. For example, PD-L1-specific CAR-T cells lysed all tested myeloid cell types that expressed PD-L1, including M0 macrophages (Mø0), LPS-polarized Mø1, IFN-γ polarized Mø1, IL-4 polarized Mø2, monocytes, immature dendritic cells (imDCs), mature DCs, as well as KG-1 AML cells, while the dual CAR-T cells displaying killing activity only towards LPS polarized Mø1, mature DCs and KG-1 cells that expressed both NKG2D ligands and PD-L1. In a mouse liquid tumor model, the dual CAR-T cells were effective in eradicating established KG-1 AML xenografts. CONCLUSION: The improved cell type specificity offered by our split dual CAR-T cell system targeting paired antigens would favour the reduction of the on-target off-tumor toxicity towards normal myeloid cells during the treatment of myeloid leukaemia.

Dual CAR-T cells to treat cancers co-expressing NKG2D and PD1 ligands in xenograft models of peritoneal metastasis.

While the expression of either NKG2D ligands or PD-1 ligands has been reported in various types of cancers, the co-expression of the two sets of ligands in the same tumour tissues is still un-investigated. After examining 68 primary ovarian cancer samples, we observed around 80% of the co-expression in low grade serous and endometrioid ovarian cancer samples. We then constructed a dual CAR system that splits the conventional single-input of a 2nd generation CAR into two independent chimeric receptors, one composed of the NKG2D extracellular domain linked with DAP12 for T cell activation and another using the PD-1 extracellular domain linked with 4-1BB for costimulatory signal 2 input. Given the limitation of the low-affinity PD-1 receptor in recognizing cancer cells with low levels of PD-1 ligands, we also used a high-affinity scFv specific to PD-L1 in our combinatorial approach to expand the range of target cancer cells with different expression levels of PD-L1. The two types of dual CAR-T cells were generated through electroporation of non-viral piggyBac transposon plasmids and were effective in eliminating the target cancer cells. Especially, the dual CAR-T cells with anti-PD-L1 scFv were capable of eradicating established tumors in mouse models of peritoneal metastasis of colorectal cancer and ovarian cancer. Since both NKG2D ligands and PD-1 ligands have been marked as favourable cancer therapeutic targets, the new dual CAR-T cells developed in this study hold attractive application potential in treating metastatic peritoneal carcinoma.

The Conceptual Development of a Multifunctional Stepladder for Older People and Caregivers.

Stepladders are compact, foldable ladders with flat steps and a platform. Despite all the research and design efforts, there are still limitations in terms of the multifunctionality, usability and simplicity of stepladders and related variants. By combining ideas, features and functions from patent literature, existing products and scientific journals, this study aims to conceptualise a multifunctional stepladder for improved usability. Five concepts are created, which are screened and evaluated against a set of criteria to select the best concept for improved usability, divided into three categories: simplicity, effectiveness and efficiency. The result is a versatile invention that functions as a stepladder, walker, wheelchair and Pilates chair, suitable for older people and caregivers in nursing homes. It allows medical records or supplies to be retrieved from high places without the need for inappropriate aids. The invention can replace wheelchairs and walkers and converts into a Pilates chair to provide a mobile exercise option for older people. The concept offers older people flexibility and independence in terms of mobility and healthcare, while saving space in the nursing home. Further design studies, prototyping and testing are needed before this idea can go into production.

An update on the prevalence, chronicity, and severity of atopic dermatitis and the associated epidemiological risk factors in the Singapore/Malaysia Chinese young adult population: A detailed description of the Singapore/Malaysia Cross-Sectional Genetics Epidemiology Study (SMCGES) cohort.

Background: Atopic Dermatitis (AD) is a highly pruritic, chronic-recurrent inflammatory skin condition associated with erythematous lesions that affect a significant proportion of the population. Although AD is a non-communicable disease, it can cause pain, unbearable itchiness, sleep disturbance, loss of work productivity, and reduced quality of life. As a heterogeneous disease, AD is influenced by multiple genes and environmental triggers. As such, it is imperative to gain a deeper insight into the intricate gene-environment relationship that results in the manifestation of AD. Methods: There are 3 objectives in our study. We first aim to update the epidemiological status of AD amongst young adults in Singapore and Malaysia, in particular amongst the Chinese ethnic background. Next, we re-evaluated the possible associated risk factors, identified in our previous meta-analysis and review studies, on the current cohort. Finally, we described here a detailed disease presentation and symptoms profile of our Singapore and Malaysia Cross-Sectional Genetics Epidemiology Study (SMCGES) cohort, which forms the base population for the discovery of associated genetic factors in relation to asthma, allergic diseases and skin conditions. Based on a skin prick test (SPT) and investigator-administered medical history responses, we assessed the AD profiles of 11 494 participants and the significant modifiable and non-modifiable factors associated with disease presentation. Results: The prevalence of AD in the combined population was 13.5%. Chronic and moderate/severe AD were observed in 35.5% and 40.5% of the individuals with AD, respectively. Family history of atopic diseases, prior history of drug allergies, a history of acne, increased household family monthly income, higher number of individuals in the shared household, parental education, sedentary lifestyle, physical activities, alcoholic consumption, and even quality of diet was significantly associated with AD presentation, chronicity, and severity. Among all the factors evaluated, family and personal history of atopic diseases imposed the strongest associated risk. Conclusions: These findings supported our previous review studies and affirmed that familial history or genetic factors critically influence the development of AD in our population and environment. Environmental and other modifiable factors can also trigger AD throughout the lifetime of individuals who have especially inherited the atopic disease disposition. A better understanding of how these risk factors affect AD individuals in our population can facilitate disease surveillance, monitor disease control, and serve as a description for our future genetic epidemiology studies.

Allergic rhinitis in Chinese young adults from the Singapore/Malaysia cross-sectional genetics epidemiology study (SMCGES) cohort: Prevalence, patterns, and epidemiology of allergic rhinitis.

Background: Allergic rhinitis (AR) is characterized by the occurrence of at least 2 symptoms of nasal itching, nasal blockage, rhinorrhea, and sneezing, when not afflicted with a cold or flu, with defined atopic sensitization demonstrated by skin prick test or specific IgE responses. Besides the detriment to standard of living and economic burden of AR, both multicentre and single-cohort studies have observed an increase in AR prevalence in Asia over time. Methods: In total, 12 872 individuals, with mean age 22.1 years (SD = 4.8), were recruited from universities in Singapore and Malaysia. Each participant provided epidemiological data based on an investigator-administered questionnaire adapted from the validated International Study of Allergies and Asthma in Childhood (ISAAC) protocol, and atopy status was determined using a skin prick test (SPT) performed by qualified staff. AR was diagnosed according to Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines and a positive SPT result. Results: Sensitization (determined by SPT) to either Blomia tropicalis or Dermatophagoides pteronyssinus was prevalent in 66.5% of the cohort. Current rhinitis (manifesting ≥2 rhinitis symptoms, within the past 12 months) was observed in 48.9% of our population, while AR, which included atopy status, was estimated at 39.4%. Sneezing and rhinorrhea were the most common symptoms among AR cases. AR prevalence decreased with increasing age (OR: 0.979; 95% CI: 0.969-0.989), while male gender (OR: 2.053; 95% CI: 1.839-2.294), and a parental history of allergic diseases (OR: 2.750; 95% CI: 2.284-3.316) were significant risk factors for AR. Upon adjustment for age, gender, and parental history, housing type (OR: 0.632; 95% CI: 0.543-0.736) and income level (>$6000 vs <$2000; OR: 2.461; 95% CI: 2.058-2.947) remained as significant risk factors for AR, while ever having kept a pet (OR: 1.167; 95% CI: 1.025-1.328) emerged as a risk factor. Conflicting results were obtained for indicators of sedentary lifestyle: frequent physical activity (OR: 1.394; 95% CI: 1.150-1.694) and increased duration spent using the TV/computer (OR: 1.224; 95% CI: 1.006-1.489) both increased the risk of AR. Lastly, we used the Quality of Diet based on Glycaemic Index Score (QDGIS) to assess the Glycaemic Index (GI) level of overall diet. We identified lower GI level of overall diet as a protective factor against AR manifestation (OR: 0.682; 95% CI: 0.577-0.807). Conclusion: While the previously established non-modifiable risk factors for AR were present in our study population, the identification of modifiable risk factors, such as TV/computer usage, and dietary habits, opens a new area for research, both in the areas of gene-environment interaction, and management of AR.

Wearable technology for early detection of COVID-19: A systematic scoping review.

Wearable technology is an emerging method for the early detection of coronavirus disease 2019 (COVID-19) infection. This scoping review explored the types, mechanisms, and accuracy of wearable technology for the early detection of COVID-19. This review was conducted according to the five-step framework of Arksey and O'Malley. Studies published between December 31, 2019 and December 15, 2021 were obtained from 10 electronic databases, namely, PubMed, Embase, Cochrane, CINAHL, PsycINFO, ProQuest, Scopus, Web of Science, IEEE Xplore, and Taylor & Francis Online. Grey literature, reference lists, and key journals were also searched. All types of articles describing wearable technology for the detection of COVID-19 infection were included. Two reviewers independently screened the articles against the eligibility criteria and extracted the data using a data charting form. A total of 40 articles were included in this review. There are 22 different types of wearable technology used to detect COVID-19 infections early in the existing literature and are categorized as smartwatches or fitness trackers (67%), medical devices (27%), or others (6%). Based on deviations in physiological characteristics, anomaly detection models that can detect COVID-19 infection early were built using artificial intelligence or statistical analysis techniques. Reported area-under-the-curve values ranged from 75% to 94.4%, and sensitivity and specificity values ranged from 36.5% to 100% and 73% to 95.3%, respectively. Further research is necessary to validate the effectiveness and clinical dependability of wearable technology before healthcare policymakers can mandate its use for remote surveillance.

Vγ9Vδ2 T cells expressing a BCMA-Specific chimeric antigen receptor inhibit multiple myeloma xenograft growth.

Vγ9Vδ2 T cells are immune effector cells capable of killing multiple myeloma (MM) cells and have been tested in clinical trials to treat MM patients. To enhance the MM cell killing function of Vγ9Vδ2 T cells, we introduced a BCMA-specific CAR into ex vivo expanded Vγ9Vδ2 T cells through electroporation of the CAR-encoding mRNA. The modified Vγ9Vδ2 T cells displayed a high cytolytic activity against BCMA-expressing MM cell lines in vitro, while sparing BCMA-negative cells, including normal B cells and monocytes. Subsequently, we intravenously injected KMS-11 human MM cells to generate a xenograft mouse model. The treatment of the tumor-bearing mice with Zometa and anti-BCMA CAR- Vγ9Vδ2 T cells resulted in a significant reduction of tumor burden in the femur region, as well as the overall tumor burden. In association with the decrease in tumor burden, the survival of the MM cell-inoculated mice was markedly prolonged. Considering the potential of Vγ9Vδ2 T cells to be used as off-the-shelf products, the modification of these cells with a BCMA-specific CAR could be an attractive option for cancer immunotherapy against bone marrow cancer MM.

Golgin A7 family member B (GOLGA7B) is a plausible novel gene associating high glycaemic index diet with acne vulgaris.

While the IGF1/FoxO1/mTORC1 signalling pathway is a well-established nutrigenomic link between high glycaemic index (GI)/glycaemic load (GL) diet and acne vulgaris, other signalling pathways remain elusive. Therefore, we aimed to investigate other genes that are involved in the high GI/GL diet-acne link, using our Singapore/Malaysia population epidemiological, genomics and transcriptomics data. High GI/GL dietary habit of 3207 acne cases (1869 and 1341 further classified into severity and scarring grades, respectively) and 2521 controls were evaluated based on Quality of Diet based on Glycaemic Index Score (QDGIS). Overlapping concordant differentially expressed genes (DEGs) between acne case-controls and QDGIS poor-moderate/good classes were identified from whole-transcriptome sequencing data of PBMC of a subset of participants. Finally, we assessed the expression quantitative trait loci (eQTL) association of single nucleotide polymorphisms (SNPs) of the concordant DEGs. Daily intake of fruits significantly reduced the risk of acne presentation, severity and scarring by up to 48.5%. Those with good QDGIS had significantly lower risk of mild and moderate/severe acne, and grade 1/2 acne scarring. Sequential filtering identified four overlapping concordant DEGs that were significantly associated with acne and QDGIS, namely GOLGA7B, SNCB, LOC102723849 and LOC283683. Combining transcriptome and genetic association data, we identified intronic SNP rs1953947 in GOLGA7B as an eQTL for acne. In conclusion, we identified GOLGA7B as a plausible novel gene that links high GI/GL with acne, and hence propose a model for the involvement of Golga7b in high GI/GL diet-acne pathogenesis, which includes palmitoyl acyltransferase zDHHC5, fatty acid translocase CD36 and palmitic acid.

A CD123-specific chimeric antigen receptor augments anti-acute myeloid leukemia activity of Vγ9Vδ2 T cells.

Aim: To investigate whether anti-CD123 chimeric antigen receptor (CAR)-expressing Vγ9Vδ2 T cells could be an alternative for acute myeloid leukemia (AML) treatment. Materials & methods:Ex vivo expanded Vγ9Vδ2 T cells were electroporated with anti-CD123 CAR-encoding mRNA. The effector function and specificity of the modified Vγ9Vδ2 T cells were examined by in vitro cytotoxicity, degranulation and cytokine release level. The in vivo function was analyzed using the xenograft KG1-luc model with NOD-SCID-γc-/- mice. Results: The modified Vγ9Vδ2 T cells exhibited significantly improved effector activities against both AML cell lines and primary AML cells in vitro. In the xenograft mouse model, the modified Vγ9Vδ2 cells displayed an enhanced tumor control potency. Conclusion: Anti-CD123 CAR-expressing Vγ9Vδ2 T cells may serve as an alternative way to target AML.