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"Li, Ryan"
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Wearable sensors for monitoring the physiological and biochemical profile of the athlete
Athletes are continually seeking new technologies and therapies to gain a competitive edge to maximize their health and performance. Athletes have gravitated toward the use of wearable sensors to monitor their training and recovery. Wearable technologies currently utilized by sports teams monitor both the internal and external workload of athletes. However, there remains an unmet medical need by the sports community to gain further insight into the internal workload of the athlete to tailor recovery protocols to each athlete. The ability to monitor biomarkers from saliva or sweat in a noninvasive and continuous manner remain the next technological gap for sports medical personnel to tailor hydration and recovery protocols per the athlete. The emergence of flexible and stretchable electronics coupled with the ability to quantify biochemical analytes and physiological parameters have enabled the detection of key markers indicative of performance and stress, as reviewed in this paper.
Journal Article
Contemporary Treatment of Locally Advanced Oral Cancer
At our institution, locally advanced oral cancer is most commonly treated with surgical resection, immediate reconstruction, and adjuvant radiotherapy with or without concurrent systemic therapy depending on final surgical pathologic analysis. There are patients with markedly advanced local or regional disease who unfortunately will have a low probability of cure. We counsel these patients on induction chemotherapy, emphasizing that this is unlikely to result in a smaller volume of surgical resection. In these patients, a good response to induction chemotherapy is more frequently followed by concurrent chemoradiotherapy. We have not been in the practice of commonly recommending definitive chemoradiotherapy for locally advanced oral cancer when upfront surgery is an option. However, as reviewed below, there is a significant rationale for definitive chemoradiotherapy in patients who are surgical candidates, with the hope of good oncologic outcomes, and potential functional organ preservation. The experts who report their experiences in the studies reviewed below provide a strong argument for considering this approach.
Journal Article
Treatment for mild cognitive impairment: systematic review
More people are presenting with mild cognitive impairment (MCI), frequently a precursor to dementia, but we do not know how to reduce deterioration.
To systematically review randomised controlled trials (RCTs) evaluating the effects of any intervention for MCI on cognitive, neuropsychiatric, functional, global outcomes, life quality or incident dementia.
We reviewed 41 studies fitting predetermined criteria, assessed validity using a checklist, calculated standardised outcomes and prioritised primary outcome findings in placebo-controlled studies.
The strongest evidence was that cholinesterase inhibitors did not reduce incident dementia. Cognition improved in single trials of: a heterogeneous psychological group intervention over 6 months; piribedil, a dopamine agonist over 3 months; and donepezil over 48 weeks. Nicotine improved attention over 6 months. There was equivocal evidence that Huannao Yicong improved cognition and social functioning.
There was no replicated evidence that any intervention was effective. Cholinesterase inhibitors and rofecoxib are ineffective in preventing dementia. Further good-quality RCTs are needed and preliminary evidence suggests these should include trials of psychological group interventions and piribedil.
Journal Article
Wearable sensors for monitoring the internal and external workload of the athlete
The convergence of semiconductor technology, physiology, and predictive health analytics from wearable devices has advanced its clinical and translational utility for sports. The detection and subsequent application of metrics pertinent to and indicative of the physical performance, physiological status, biochemical composition, and mental alertness of the athlete has been shown to reduce the risk of injuries and improve performance and has enabled the development of athlete-centered protocols and treatment plans by team physicians and trainers. Our discussions in this review include commercially available devices, as well as those described in scientific literature to provide an understanding of wearable sensors for sports medicine. The primary objective of this paper is to provide a comprehensive review of the applications of wearable technology for assessing the biomechanical and physiological parameters of the athlete. A secondary objective of this paper is to identify collaborative research opportunities among academic research groups, sports medicine health clinics, and sports team performance programs to further the utility of this technology to assist in the return-to-play for athletes across various sporting domains. A companion paper discusses the use of wearables to monitor the biochemical profile and mental acuity of the athlete.
Journal Article
Increasing Precipitation Efficiency Amplifies Climate Sensitivity by Enhancing Tropical Circulation Slowdown and Eastern Pacific Warming Pattern
The role of precipitation efficiency (PE)—the fraction of column‐integrated condensate that reaches the surface as rain—in the global temperature response to CO2 rise is yet to be quantified. Here we employ 36 limited‐domain cloud resolving models (CRMs) from the Radiative‐Convective Equilibrium Model Intercomparison Project and find that they strongly imply higher PE at warmer temperatures. We then analyze 35 general circulation models (GCMs) from the Coupled Model Intercomparison Project Phase 6 and find that increasing PE is associated with tropical circulation slowdown and greater eastern equatorial Pacific warming. These changes trigger pan‐tropical positive cloud feedback through stratiform anvil cloud reduction and stratocumulus suppression, resulting in higher Effective Climate Sensitivity (ECS). We find that in 24 of 35 GCMs matching the CRMs in simulating increasing PE with greenhouse warming, mean ECS is 1 K higher than in PE‐decreasing GCMs. Thus, further constraining PE sensitivity to temperature could reduce uncertainty over future climate projections. Plain Language Summary Precipitation efficiency (PE) is the ratio of precipitation to cloud condensate. Evidence from the great majority of cloud‐resolving models and many earth system models support higher PE with warming. With higher PE, more cloud condensate leaves the atmosphere as precipitation, reducing cloud cover and optical thickness. As PE is tightly linked to the latent heat release of tropical convection, an atmosphere with high PE and a weak circulation can release the same latent heat as its counterpart with low PE and strong circulation. Increasing PE is robustly correlated with pan‐tropical positive cloud feedback in the equatorial Pacific, namely thinner stratiform anvil clouds in the west and suppressed stratocumulus cloud cover in the east. Hence, quantifying PE change is critical for climate projections. Key Points Cloud‐resolving models indicate increasing precipitation efficiency with global warming High precipitation efficiency implies a weak Walker circulation, eastern tropical Pacific warming, and positive tropical cloud feedback All 4 K or higher climate sensitivity climate models project increasing precipitation efficiency
Journal Article
Precipitation efficiency constraint on climate change
Precipitation efficiency (PE) relates cloud condensation to precipitation and intrinsically binds atmospheric circulation to the hydrological cycle. Due to PE’s inherent microphysical dependencies, definitions and estimates vary immensely. Consequently, PE’s sensitivity to greenhouse warming and implications for climate change are poorly understood. Here, we quantify PE’s role in climate change by defining a simple index ϵ as the ratio of surface precipitation to condensed water path. This macroscopic metric is reconcilable with microphysical PE measures and higher ϵ is associated with stronger mean Walker circulation. We further find that state-of-the-art climate models disagree on the sign and magnitude of future ϵ changes. This sign disagreement originates from models’ convective parameterizations. Critically, models with increasing ϵ under greenhouse warming, in line with cloud-resolving simulations, show greater slowdown of the large-scale Hadley and Walker circulations and a two-fold greater increase in extreme rainfall than models with decreasing ϵ.Falling raindrops play an essential but as-yet unquantified role in planetary climate change. Here the authors use the concept of precipitation efficiency to establish that raindrops play a critical role in predicting future tropical atmospheric circulation and extreme precipitation.
Journal Article
Novel Insight into Mutational Landscape of Head and Neck Squamous Cell Carcinoma
Development of head and neck squamous cell carcinoma (HNSCC) is characterized by accumulation of mutations in several oncogenes and tumor suppressor genes. We have formerly described the mutation pattern of HNSCC and described NOTCH signaling pathway alterations. Given the complexity of the HNSCC, here we extend the previous study to understand the overall HNSCC mutation context and to discover additional genetic alterations. We performed high depth targeted exon sequencing of 51 highly actionable cancer-related genes with a high frequency of mutation across many cancer types, including head and neck. DNA from primary tumor tissues and matched normal tissues was analyzed for 37 HNSCC patients. We identified 26 non-synonymous or stop-gained mutations targeting 11 of 51 selected genes. These genes were mutated in 17 out of 37 (46%) studied HNSCC patients. Smokers harbored 3.2-fold more mutations than non-smokers. Importantly, TP53 was mutated in 30%, NOTCH1 in 8% and FGFR3 in 5% of HNSCC. HPV negative patients harbored 4-fold more TP53 mutations than HPV positive patients. These data confirm prior reports of the HNSCC mutational profile. Additionally, we detected mutations in two new genes, CEBPA and FES, which have not been previously reported in HNSCC. These data extend the spectrum of HNSCC mutations and define novel mutation targets in HNSCC carcinogenesis, especially for smokers and HNSCC without HPV infection.
Journal Article
Robotic microinjection enables large-scale transgenic studies of Caenorhabditis elegans
The nematode
Caenorhabditis elegans
is widely employed as a model organism to study basic biological mechanisms. However, transgenic
C. elegans
are generated by manual injection, which remains low-throughput and labor-intensive, limiting the scope of approaches benefitting from large-scale transgenesis. Here, we report a robotic microinjection system, integrating a microfluidic device capable of reliable worm immobilization, transfer, and rotation, for high-speed injection of
C. elegans
. The robotic system provides an injection speed 2-3 times faster than that of experts with 7–22 years of experience while maintaining comparable injection quality and only limited trials needed by users to become proficient. We further employ our system in a large-scale reverse genetic screen using multiplexed alternative splicing reporters, and find that the TDP-1 RNA-binding protein regulates alternative splicing of
zoo-1
mRNA, which encodes variants of the zonula occludens tight junction proteins. With its high speed, high accuracy, and high efficiency in worm injection, this robotic system shows great potential for high-throughput transgenic studies of
C. elegans
.
Manual injection, which remains low-throughput and labor-intensive, is a technical bottleneck for large-scale genetic studies of C. elegans. Here, the authors report a robotic microinjection system which facilitates injection speed while maintaining injection quality which is comparable to experienced experts.
Journal Article
Exome Sequencing of Head and Neck Squamous Cell Carcinoma Reveals Inactivating Mutations in NOTCH1
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. To explore the genetic origins of this cancer, we used whole-exome sequencing and gene copy number analyses to study 32 primary tumors. Tumors from patients with a history of tobacco use had more mutations than did tumors from patients who did not use tobacco, and tumors that were negative for human papillomavirus (HPV) had more mutations than did HPV-positive tumors. Six of the genes that were mutated in multiple tumors were assessed in up to 88 additional HNSCCs. In addition to previously described mutations in TP53, CDKN2A, PIK3CA, and HRAS, we identified mutations in FBXW7 and NOTCH1. Nearly 40% of the 28 mutations identified in NOTCH1 were predicted to truncate the gene product, suggesting that NOTCH1 may function as a tumor suppressor gene rather than an oncogene in this tumor type.
Journal Article