The Emergent Landscape of Detecting EGFR Mutations Using Circulating Tumor DNA in Lung Cancer.

The advances in targeted therapies for lung cancer are based on the evaluation of specific gene mutations especially the epidermal growth factor receptor (EGFR). The assays largely depend on the acquisition of tumor tissue via biopsy before the initiation of therapy or after the onset of acquired resistance. However, the limitations of tissue biopsy including tumor heterogeneity and insufficient tissues for molecular testing are impotent clinical obstacles for mutation analysis and lung cancer treatment. Due to the invasive procedure of tissue biopsy and the progressive development of drug-resistant EGFR mutations, the effective initial detection and continuous monitoring of EGFR mutations are still unmet requirements. Circulating tumor DNA (ctDNA) detection is a promising biomarker for noninvasive assessment of cancer burden. Recent advancement of sensitive techniques in detecting EGFR mutations using ctDNA enables a broad range of clinical applications, including early detection of disease, prediction of treatment responses, and disease progression. This review not only introduces the biology and clinical implementations of ctDNA but also includes the updating information of recent advancement of techniques for detecting EGFR mutation using ctDNA in lung cancer

AV2Wav: Diffusion-Based Re-synthesis from Continuous Self-supervised Features for Audio-Visual Speech Enhancement

Speech enhancement systems are typically trained using pairs of clean and noisy speech. In audio-visual speech enhancement (AVSE), there is not as much ground-truth clean data available; most audio-visual datasets are collected in real-world environments with background noise and reverberation, hampering the development of AVSE. In this work, we introduce AV2Wav, a resynthesis-based audio-visual speech enhancement approach that can generate clean speech despite the challenges of real-world training data. We obtain a subset of nearly clean speech from an audio-visual corpus using a neural quality estimator, and then train a diffusion model on this subset to generate waveforms conditioned on continuous speech representations from AV-HuBERT with noise-robust training. We use continuous rather than discrete representations to retain prosody and speaker information. With this vocoding task alone, the model can perform speech enhancement better than a masking-based baseline. We further fine-tune the diffusion model on clean/noisy utterance pairs to improve the performance. Our approach outperforms a masking-based baseline in terms of both automatic metrics and a human listening test and is close in quality to the target speech in the listening test. Audio samples can be found at https://home.ttic.edu/~jcchou/demo/avse/avse_demo.html.Comment: Submitted to ICASSP 202

Few-Shot Spoken Language Understanding via Joint Speech-Text Models

Recent work on speech representation models jointly pre-trained with text has demonstrated the potential of improving speech representations by encoding speech and text in a shared space. In this paper, we leverage such shared representations to address the persistent challenge of limited data availability in spoken language understanding tasks. By employing a pre-trained speech-text model, we find that models fine-tuned on text can be effectively transferred to speech testing data. With as little as 1 hour of labeled speech data, our proposed approach achieves comparable performance on spoken language understanding tasks (specifically, sentiment analysis and named entity recognition) when compared to previous methods using speech-only pre-trained models fine-tuned on 10 times more data. Beyond the proof-of-concept study, we also analyze the latent representations. We find that the bottom layers of speech-text models are largely task-agnostic and align speech and text representations into a shared space, while the top layers are more task-specific

RISK OF SLEEP DISORDERS IN PATIENTS WITH DECOMPRESSION SICKNESS: A NATIONWIDE, POPULATION-BASED STUDY IN TAIWAN

Background: Decompression sickness (DCS) primarily manifests musculoskeletal pain, cutaneous manifestations, lymphatic symptoms, and neurological symptoms. DCS might affect the central nervous system and induce the stress in the patients, but few studies about the psychiatric morbidity after DCS have been conducted. This study aimed to investigate the association between DCS and the risk of developing psychiatric disorders. Subjects and methods: This study was a population-based, matched cohort design. A total of 738 enrolled patients, with 123 study subjects who had suffered from DCS, and 615 controls matched for sex and age, from the Longitudinal Health Insurance Databank from 2000-2010 in Taiwan, and selected from the National Health Insurance Research Database. After adjusting for the confounding factors, Cox proportional hazards analysis was used to compare the risk of developing psychiatric disorders during the 10 years of follow-up period. Results: Of the study subjects, 10 (8.13%) developed psychiatric disorders when compared to 35 (5.69%) in the control group. The study subjects were more likely to develop psychiatric disorders (crude hazard ratio [HR]: 2.79 (95% CI=1.37-5.69, P<0.01). After adjusting for sex, age, monthly income, urbanization level, geographic region, and comorbidities, the adjusted HR was 3.83 (95% CI=1.60-9.16, P<0.01). Sleep disorders was associated with DCS with the adjusted HR as 5.74 (95% CI=1.04-31.56, P<0.01). Hyperbaric oxygenation therapy was not associated with a lower risk of psychiatric disorders. Conclusions: Patients who suffered from DCS have a 3.8-fold risk of developing psychiatric disorders, and a 5.7-fold risk of sleep disorders. This finding is a reminder for the clinicians that a regular psychiatric follow-up might well be needed for these patients

Liquid biopsy genotyping in lung cancer: ready for clinical utility?

Liquid biopsy is a blood test that detects evidence of cancer cells or tumor DNA in the circulation. Despite complicated collection methods and the requirement for technique-dependent platforms, it has generated substantial interest due, in part, to its potential to detect driver oncogenes such as epidermal growth factor receptor (EGFR) mutants in lung cancer. This technology is advancing rapidly and is being incorporated into numerous EGFR tyrosine kinase inhibitor (EGFR-TKI) development programs. It appears ready for integration into clinical care. Recent studies have demonstrated that biological fluids such as saliva and urine can also be used for detecting EGFR mutant DNA through application other user-friendly techniques. This review focuses on the clinical application of liquid biopsies to lung cancer genotyping, including EGFR and other targets of genotype-directed therapy and compares multiple platforms used for liquid biopsy

Reduction in patient burdens with graphical computerized adaptive testing on the ADL scale: tool development and simulation

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to verify the effectiveness and efficacy of saving time and reducing burden for patients, nurses, and even occupational therapists through computer adaptive testing (CAT).</p> <p>Methods</p> <p>Based on an item bank of the Barthel Index (BI) and the Frenchay Activities Index (FAI) for assessing comprehensive activities of daily living (ADL) function in stroke patients, we developed a visual basic application (VBA)-Excel CAT module, and (1) investigated whether the averaged test length via CAT is shorter than that of the traditional all-item-answered non-adaptive testing (NAT) approach through simulation, (2) illustrated the CAT multimedia on a tablet PC showing data collection and response errors of ADL clinical functional measures in stroke patients, and (3) demonstrated the quality control of endorsing scale with fit statistics to detect responding errors, which will be further immediately reconfirmed by technicians once patient ends the CAT assessment.</p> <p>Results</p> <p>The results show that endorsed items could be shorter on CAT (<it>M </it>= 13.42) than on NAT (<it>M </it>= 23) at 41.64% efficiency in test length. However, averaged ability estimations reveal insignificant differences between CAT and NAT.</p> <p>Conclusion</p> <p>This study found that mobile nursing services, placed at the bedsides of patients could, through the programmed VBA-Excel CAT module, reduce the burden to patients and save time, more so than the traditional NAT paper-and-pencil testing appraisals.</p

Intraclass reliability for assessing how well Taiwan constrained hospital-provided medical services using statistical process control chart techniques

BACKGROUND: Few studies discuss the indicators used to assess the effect on cost containment in healthcare across hospitals in a single-payer national healthcare system with constrained medical resources. We present the intraclass correlation coefficient (ICC) to assess how well Taiwan constrained hospital-provided medical services in such a system. METHODS: A custom Excel-VBA routine to record the distances of standard deviations (SDs) from the central line (the mean over the previous 12 months) of a control chart was used to construct and scale annual medical expenditures sequentially from 2000 to 2009 for 421 hospitals in Taiwan to generate the ICC. The ICC was then used to evaluate Taiwan’s year-based convergent power to remain unchanged in hospital-provided constrained medical services. A bubble chart of SDs for a specific month was generated to present the effects of using control charts in a national healthcare system. RESULTS: ICCs were generated for Taiwan’s year-based convergent power to constrain its medical services from 2000 to 2009. All hospital groups showed a gradually well-controlled supply of services that decreased from 0.772 to 0.415. The bubble chart identified outlier hospitals that required investigation of possible excessive reimbursements in a specific time period. CONCLUSION: We recommend using the ICC to annually assess a nation’s year-based convergent power to constrain medical services across hospitals. Using sequential control charts to regularly monitor hospital reimbursements is required to achieve financial control in a single-payer nationwide healthcare system

The effects of rear-wheel camber on the kinematics of upper extremity during wheelchair propulsion

BACKGROUND: The rear-wheel camber, defined as the inclination of the rear wheels, is usually used in wheelchair sports, but it is becoming increasingly employed in daily propulsion. Although the rear-wheel camber can increase stability, it alters physiological performance during propulsion. The purpose of the study is to investigate the effects of rear-wheel cambers on temporal-spatial parameters, joint angles, and propulsion patterns. METHODS: Twelve inexperienced subjects (22.3±1.6 yr) participated in the study. None had musculoskeletal disorders in their upper extremities. An eight-camera motion capture system was used to collect the three-dimensional trajectory data of markers attached to the wheelchair-user system during propulsion. All participants propelled the same wheelchair, which had an instrumented wheel with cambers of 0°, 9°, and 15°, respectively, at an average velocity of 1 m/s. RESULTS: The results show that the rear-wheel camber significantly affects the average acceleration, maximum end angle, trunk movement, elbow joint movement, wrist joint movement, and propulsion pattern. The effects are especially significant between 0° and 15°. For a 15° camber, the average acceleration and joint peak angles significantly increased (p < 0.01). A single loop pattern (SLOP) was adopted by most of the subjects. CONCLUSIONS: The rear-wheel camber affects propulsion patterns and joint range of motion. When choosing a wheelchair with camber adjustment, the increase of joint movements and the base of support should be taken into consideration

Measurements of Natural Carbonate Rare Earth Elements in Femtogram Quantities by Inductive Coupled Plasma Sector Field Mass Spectrometry

A rapid and precise standard-bracketing method has been developed for measuring femtogram quantity rare earth element (REE) levels in natural carbonate samples by inductively coupled plasma sector field mass spectrometry that does not require chemical separation steps. A desolvation nebulization system was used to effectively reduce polyatomic interference and enhance sensitivity. REE/Ca ratios are calculated directly from the intensities of the ion beams of 46Ca, 139La, 140Ce, 141Pr, 146Nd, 147Sm, 153Eu, 160Gd, 159Tb, 163Dy, 165Ho, 166Er, 169Tm, 172Yb, and 175Lu using external matrix-matched synthetic standards to correct for instrumental ratio drifting and mass discrimination. A routine measurement time of 3 min is typical for one sample containing 20-40 ppm Ca. Replicate measurements made on natural coral and foraminiferal samples with REE/Ca ratios of 2-242 nmol/mol show that external precisions of 1.9-6.5% (2 RSD) can be achieved with only 10-1000 fg of REEs in 10-20 μg of carbonate. We show that different sources for monthly resolved coral ultratrace REE variability can be distinguished using this method. For natural slow growth-rate carbonate materials, such as sclerosponges, tufa, and speleothems, the high sample throughput, high precision, and high temporal resolution REE records that can be produced with this procedure have the potential to provide valuable time-series records to advance our understanding of paleoclimatic and paleoenvironmental dynamics on different time scales