Identification of Respiratory Sounds Collected from Microphones Embedded in Mobile Phones

Sudden deterioration of condition in patients with various diseases, such as cardiopulmonary arrest, may result in poor outcome even after resuscitation. Early detection of deterioration is important in medical and long-term care settings, regardless of the acute or chronic phase of disease. Early detection and appropriate interventions are essential before resuscitating measures are required. Among the vital signs that indicate the general condition of a patient, respiratory rate has a greater ability to predict serious events such as thromboembolism and sepsis than heart rate and blood pressure, even in early stages. Despite its importance, however, respiratory rate is frequently overlooked and not measured, making it a neglected vital sign. To facilitate the measurement of respiratory rate, a non-invasive method of detecting respiratory sounds was developed based on deep learning technology, using a built-in microphone in a smartphone. Smartphones attached to the bed headboards of 20 participants undergoing polysomnography (PSG) at Kyoto University Hospital recorded respiratory sounds. Sound data were synchronized with overnight respiratory information. After excluding periods of abnormal breathing on the PSG report, sound data were processed for each 1-minute period. Expiration sound was determined using the pressure flow sensor signal on PSG. Finally, a model to identify the expiration section from the sound information was created using a deep learning algorithm from the convolutional Long Short Term Memory network. The accuracy of the learning model in identifying the expiratory section was 0.791, indicating that respiratory rate can be determined using the microphone in a smartphone. By collecting data from more patients and improving the accuracy of this method, respiratory rates could be more easily monitored in all situations, both inside and outside the hospital

Serotonin transporter gene polymorphism may be associated with functional dyspepsia in a Japanese population

<p>Abstract</p> <p>Background</p> <p>Although familial clustering of functional dyspepsia (FD) has been reported, the role of genetics in the susceptibility to FD is still not well understood. In the present study, the association between serotonin transporter (SERT) gene (<it>SLC6A4</it>) polymorphism and FD was explored.</p> <p>Methods</p> <p>Subjects were divided into either a postprandial distress syndrome (PDS) group or an epigastric pain syndrome (EPS) group according to the Rome III criteria. The healthy controls were those who had visited a hospital for an annual health check-up. The presence of the <it>SLC6A4 </it>promoter polymorphism, <it>5-hydroxytryptamin transporter gene linked polymorphic region </it>(<it>5-HTTLPR</it>), was then evaluated, and logistic regression analysis was used to test all variables.</p> <p>Results</p> <p>The <it>5-HTTLPR </it>genotype distribution was 448 SS, 174 SL, and 24 LL in controls and 30 SS, 20 SL, and 3 LL in FD subjects. No significant correlation was found between the <it>5-HTTLPR </it>genotype and FD. When the genotypes and subtypes of FD were exploratory evaluated, the SL genotype was significantly associated with PDS [odds ratio (OR) = 2.24, 95% confidence interval (CI); 1.16-4.32, <it>P </it>= 0.034 after Bonferroni correction] compared to the SS genotype adjusted for sex and age. Comparison of the SS genotype with the SL/LL genotype also showed a significant association of genotype with PDS (OR = 2.32, 95% CI; 1.23-4.37, <it>P </it>= 0.009).</p> <p>Conclusion</p> <p>The present results suggest that <it>5-HTTLPR </it>L allele may influence the susceptibility to PDS.</p

Inter-assay variability of next-generation sequencing-based gene panels

BACKGROUND: Tumor heterogeneity has been known to cause inter-assay discordance among next-generation sequencing (NGS) results. However, whether preclinical factors such as sample type, sample quality and analytical features of gene panel can affect the concordance between two different assays remains largely unexplored. METHODS: Replicate sets of DNA samples extracted from formalin-fixed paraffin-embedded tissues (FFPE) (n = 20) and fresh frozen (FF) tissues (n = 10) were herein analyzed using a tumor-only (TO) and paired tumor-normal (TN) gene panel in laboratories certified by the Clinical Laboratory Improvement Amendment. Reported variants from the TO and TN panels were then compared. Furthermore, additional FFPE samples were sequentially sliced from the same FFPE block and submitted to another TN panel assay. RESULTS: Substantial discordance (71.8%) was observed between the results of the two panels despite using identical DNA samples, with the discordance rate being significantly higher for FFPE samples (p < 0.05). Among the 99 variants reported only in the TO panel, 32.3% were consistent with germline variants, which were excluded in the TN panel, while 30.3% had an allele frequency of less than 5%, some of which were highly likely to be artificial calls. The comparison of two independent TN panel assay results from the same FFPE block also showed substantial discordance rate (55.3%). CONCLUSIONS: In the context of clinical settings, our comparative analysis revealed that inter-NGS assay discordance commonly occurred due to sample types and the different analytical features of each panel

Prevalence of pathogenic germline variants in the circulating tumor DNA testing

BACKGROUND: Somatic and germline variants are not distinguishable by circulating tumor DNA (ctDNA) testing without analyzing non-tumor samples. Although confirmatory germline testing is clinically relevant, the criteria for selecting presumed germline variants have not been established in ctDNA testing. In the present study, we aimed to evaluate the prevalence of pathogenic germline variants in clinical ctDNA testing through their variant allele fractions (VAFs). METHODS: A total of consecutive 106 patients with advanced solid tumors who underwent ctDNA testing (Guardant360®) between January 2018 and March 2020 were eligible for this study. To verify the origin of pathogenic variants reported in ctDNA testing, germline sequencing was performed using peripheral blood DNA samples archived in the Clinical Bioresource Center in Kyoto University Hospital (Kyoto, Japan) under clinical research settings. RESULTS: Among 223 pathogenic variants reported in ctDNA testing, the median VAF was 0.9% (0.02-81.8%), and 88 variants with ≥ 1% VAFs were analyzed in germline sequencing. Among 25 variants with ≥ 30% VAFs, seven were found in peripheral blood DNA (BRCA2: n = 6, JAK2: n = 1). In contrast, among the 63 variants with VAFs ranging from 1 to < 30%, only one variant was found in peripheral blood DNA (TP53: n = 1). Eventually, this variant with 15.6% VAF was defined to be an acquired variant, because its allelic distribution did not completely link to those of neighboring germline polymorphisms. CONCLUSION: Our current study demonstrated that VAFs values are helpful for selecting presumed germline variants in clinical ctDNA testing

Integrating Preprocessing Operations into Deep Learning Model: Case Study of Posttreatment Visual Acuity Prediction

Designing a deep neural network model that integrates clinical images with other electronic medical records entails various preprocessing operations. Preprocessing of clinical images often requires trimming of parts of the lesions shown in the images, whereas preprocessing of other electronic medical records requires vectorization of these records; for example, patient age is often converted into a categorical vector of 10-year intervals. Although these preprocessing operations are critical to the performance of the classification model, there is no guarantee that the preprocessing step chosen is appropriate for model training. The ability to integrate these preprocessing operations into a deep neural network model and to train the model, including the preprocessing operations, can help design a multi-modal medical classification model. This study proposes integration layers of preprocessing, both for clinical images and electronic medical records, in deep neural network models. Preprocessing of clinical images is realized by a vision transformer layer that selectively adopts the parts of the images requiring attention. The preprocessing of other medical electrical records is performed by adopting full-connection layers and normalizing these layers. These proposed preprocessing-integrated layers were verified using a posttreatment visual acuity prediction task in ophthalmology as a case study. This prediction task requires clinical images as well as patient profile data corresponding to each patient's posttreatment logMAR visual acuity. The performance of a heuristically designed prediction model was compared with the performance of the prediction model that includes the proposed preprocessing integration layers. The mean square errors between predicted and correct results were 0.051 for the heuristic model and 0.054 for the proposed model. Experimental results showed that the proposed model utilizing preprocessing integration layers achieved nearly the same performance as the heuristically designed model

Large scale genotyping study for asthma in the Japanese population

<p>Abstract</p> <p>Background</p> <p>Asthma is a complex phenotype that is influenced by both genetic and environmental factors. Genome-wide linkage and association studies have been performed to identify susceptibility genes for asthma. These studies identified new genes and pathways implicated in this disease, many of which were previously unknown.</p> <p>Objective</p> <p>To perform a large-scale genotyping study to identify asthma-susceptibility genes in the Japanese population.</p> <p>Methods</p> <p>We performed a large-scale, three-stage association study on 288 atopic asthmatics and 1032 controls, by using multiplex PCR-Invader assay methods at 82,935 single nucleotide polymorphisms (SNPs) (1^ststage). SNPs that were strongly associated with asthma were further genotyped in samples from asthmatic families (216 families, 762 members, 2^ndstage), 541 independent patients, and 744 controls (3^rdstage).</p> <p>Results</p> <p>SNPs located in the 5' region of <it>PEX19 </it>(rs2820421) were significantly associated with <it>P </it>< 0.05 through the 1^stto the 3^rdstage analyses; however, the <it>P </it>values did not reach statistically significant levels (combined, <it>P </it>= 3.8 × 10^-5; statistically significant levels with Bonferroni correction, <it>P </it>= 6.57 × 10^-7). SNPs on <it>HPCAL1 </it>(rs3771140) and on <it>IL18R1 </it>(rs3213733) were associated with asthma in the 1^stand 2^ndstage analyses, but the associations were not observed in the 3^rdstage analysis.</p> <p>Conclusion</p> <p>No association attained genome-wide significance, but several loci for possible association emerged. Future studies are required to validate these results for the prevention and treatment of asthma.</p

Visceral fat obesity is the key risk factor for the development of reflux erosive esophagitis in 40–69-years subjects

[Background] Visceral fat obesity can be defined quantitatively by abdominal computed tomography, however, the usefulness of measuring visceral fat area to assess the etiology of gastrointestinal reflux disease has not been fully elucidated. [Methods] A total of 433 healthy subjects aged 40–69 years (234 men, 199 women) were included in the study. The relationship between obesity-related factors (total fat area, visceral fat area, subcutaneous fat area, waist circumference, and body mass index) and the incidence of reflux erosive esophagitis was investigated. Lifestyle factors and stomach conditions relevant to the onset of erosive esophagitis were also analyzed. [Results] The prevalence of reflux erosive esophagitis was 27.2% (118/433; 106 men, 12 women). Visceral fat area was higher in subjects with erosive esophagitis than in those without (116.6 cm2 vs. 64.9 cm2, respectively). The incidence of erosive esophagitis was higher in subjects with visceral fat obesity (visceral fat area ≥ 100 cm2) than in those without (61.2% vs. 12.8%, respectively). Visceral fat obesity had the highest odds ratio (OR) among obesity-related factors. Multivariate analysis showed that visceral fat area was associated with the incidence of erosive esophagitis (OR = 2.18), indicating that it is an independent risk factor for erosive esophagitis. In addition, daily alcohol intake (OR = 1.54), gastric atrophy open type (OR = 0.29), and never-smoking history (OR = 0.49) were also independently associated with the development of erosive esophagitis. [Conclusions] Visceral fat obesity is the key risk factor for the development of reflux erosive esophagitis in subjects aged 40–69 years

HER2 G776S mutation promotes oncogenic potential in colorectal cancer cells when accompanied by loss of APC function

Clinical cancer genome sequencing detects oncogenic variants that are potential targets for cancer treatment, but it also detects variants of unknown significance. These variants may interact with each other to influence tumor pathophysiology, however, such interactions have not been fully elucidated. Additionally, the effect of target therapy for those variants also unclarified. In this study, we investigated the biological functions of a HER2 mutation (G776S mutation) of unknown pathological significance, which was detected together with APC mutation by cancer genome sequencing of samples from a colorectal cancer (CRC) patient. Transfection of the HER2 G776S mutation alone slightly increased the kinase activity and phosphorylation of HER2 protein, but did not activate HER2 downstream signaling or alter the cell phenotype. On the other hand, the HER2 G776S mutation was shown to have strong oncogenic potential when loss of APC function was accompanied. We revealed that loss of APC function increased Wnt pathway activity but also increased RAS-GTP, which increased ERK phosphorylation triggered by HER2 G776S transfection. In addition, afatinib, a pan-HER tyrosine kinase inhibitor, suppressed tumor growth in xenografts derived from HER2 G776S-transfected CRC cells. These findings suggest that this HER2 mutation in CRC may be a potential therapeutic target

Comprehensive genomic profiling for patients with chemotherapy‐naïve advanced cancer

Comprehensive genomic profiling (CGP) testing by next-generation sequencing has been introduced into clinical practice as part of precision cancer medicine to select effective targeted therapies. However, whether CGP testing at the time of first-line chemotherapy could be clinically useful is not clear. We conducted this single-center, prospective, observational study to investigate the feasibility of CGP testing for chemotherapy-naïve patients with stage III/IV gastrointestinal cancer, rare cancer, and cancer of unknown primary, using the FoundationOne® companion diagnostic (F1CDx) assay. The primary outcome was the detection rate of at least one actionable/druggable cancer genomic alteration. Actionable/druggable cancer genomic alterations were determined by the F1CDx report. An institutional molecular tumor board determined the molecular-based recommended therapies. A total of 197 patients were enrolled from October 2018 to June 2019. CGP success rate was 76.6% (151 of 197 patients), and median turnaround time was 19 days (range: 10-329 days). Actionable and druggable cancer genomic alterations were reported in 145 (73.6%) and 124 (62.9%) patients, respectively. The highest detection rate of druggable genomic alterations in gastrointestinal cancers was 80% in colorectal cancer (48 of 60 patients). Molecular-based recommended therapies were determined in 46 patients (23.4%). CGP testing would be a useful tool for the identification of a potentially effective first-line chemotherapy

Impact of neoadjuvant intensity-modulated radiation therapy on borderline resectable pancreatic cancer with arterial abutment; a prospective, open-label, phase II study in a single institution

BACKGROUND: Borderline resectable pancreatic cancer (BRPC) is a category of pancreatic cancer that is anatomically widely spread, and curative resection is uncommon with upfront surgery. Intensity-modulated radiation therapy (IMRT) is a form of radiation therapy that delivers precise radiation to a tumor while minimizing the dose to surrounding normal tissues. Here, we conducted a phase 2 study to estimate the curability and efficacy of neoadjuvant chemoradiotherapy using IMRT (NACIMRT) for patients with BRPC with arterial abutment (BRPC-A). METHODS: A total of 49 BRPC-A patients were enrolled in this study and were treated at our hospital according to the study protocol between June 2013 and March 2021. The primary endpoint was microscopically margin-negative resection (R0) rates and we subsequently analyzed safety, histological effect of the treatment as well as survivals among patients with NACIMRT. RESULTS: Twenty-nine patients (59.2%) received pancreatectomy after NACIMRT. The R0 rate in resection patients was 93.1% and that in the whole cohort was 55.1%. No mortality was encountered. Local therapeutic effects as assessed by Evans classification showed good therapeutic effect (Grade 1, 3.4%; Grade 2a, 31.0%; Grade 2b, 48.3%; Grade 3, 3.4%; Grade 4, 3.4%). Median disease-free survival was 15.5 months. Median overall survival in the whole cohort was 35.1 months. The only independent prognostic pre-NACIMRT factor identified was serum carbohydrate antigen 19-9 (CA19-9) > 400 U/ml before NACIMRT. CONCLUSIONS: NACIMRT showed preferable outcome without significant operative morbidity for BRPC-A patients. NACIMRT contributes to good local tumor control, but a high initial serum CA19-9 implies poor prognosis even after neoadjuvant treatment. TRIAL REGISTRATION: UMIN-CTR Clinical Trial: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000011776 Registration number: UMIN000010113. Date of first registration: 01/03/2013