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Objective To prospectively compare the efficacy of conventional center-based cardiac rehabilitation (CBCR) and home-based cardiac rehabilitation (HBCR) during the coronavirus disease 2019 (COVID-19) pandemic. Methods Ninety patients were divided into HBCR and CBCR groups based on cardiovascular risk stratification and individual preference. The CBCR group performed supervised in-hospital exercise training 2–3 times/week and subsequent self-exercise at home. The HBCR group performed self-exercise at home after one or two sessions of exercise education. The cardiopulmonary exercise test results at baseline and those at the 3-, 6-, and 12-month follow-ups were analyzed as primary outcome. Results The peak oxygen consumption (peak VO2, mL/kg/min) in the CBCR group was 20.1 and 24.0 at baseline and 12 months, respectively, showing significant improvement (p=0.006). In the HBCR group, it only increased from 24.4 to 25.5, showing suboptimal improvement. A significant increase in the Korean activity scale/index was confirmed only in the CBCR group (p=0.04). The cardiovascular outcome did not differ between the two groups, nor did the dropout rate or demographic factors. Conclusion During the COVID-19 pandemic, only CBCR was associated with a significant improvement in peak VO2 and physical activity levels, a finding that differs from those of other studies and seems to be affected by COVID-19. Therefore, in situations where the importance of HBCR is emphasized, it is essential to introduce measures to monitor and enhance exercise adherence among participants.

Abstract Display has been evolving its role as a conventional optical output device into an user interactive input and output device by harnessing various sensors and taking full advantage of its user interaction friendly nature. To demonstrate this phenomenon, here we report a full organic photodiode embedded organic light-emitting diode display as multiple objects sensing platform which identifies the user’s physiological data based on the obtained photoplethysmography signal and also detects a fingerprint for an authentication concurrently in a single device. This paper introduces the technical breakthroughs to solve the complex technical challenges due to the crosstalks induced within the shared common layers during the full integration of the two conflicting devices and also the method made possible for the multiple objects sensing with the measurement results. Consequently, we believe it could prove a progression of display to a fully bidirectional innovative smart user interactive device and also could take a role as a sophisticated future display beyond organic light-emitting diode display.

Abstract In this paper, we investigate the heavy quark (HQ) mass effects on the transverse momentum dependent fragmentation function (TMDFF). We first calculate the one-loop TMDFF initiated by a heavy quark. We then investigate the HQ TMDFF in the limit where the transverse momentum, q ⊥ is small compared to the heavy quark mass, q ⊥ ≪ m and also in the opposite limit where q ⊥ ≫ m. As applications of the HQ TMDFF, we study the HQ transverse momentum dependent jet fragmentation function, where the heavy quark fragments into a jet containing a heavy hadron, and we investigate a heavy hadron’s transverse momentum dependent distribution with respect to the thrust axis in e + e − collisions.

Abstract The identification of actionable biomarkers and development of targeted therapies have revolutionized the field of lung cancer treatment. In patients with advanced non-small cell lung cancer (NSCLC), biomarker testing can inform selection of effective targeted therapies as well as avoid therapies that are less likely to be effective in certain populations. A growing number of actionable targets, including those involving EGFR, ALK, ROS1, BRAF, MET, KRAS, NTRK, RET, HER2, and PD-L1, can be identified with biomarker testing. More than half of patients with advanced NSCLC have tumors that harbor genetic alterations that can be targeted. When these patients are treated with targeted therapy, survival and quality of life may be significantly improved. In addition, broad-based molecular testing may detect alterations identifying patients who are potentially eligible for current or future clinical trials. Comprehensive biomarker testing rates in communities are often low, and turnaround times for results can be unacceptably long. There is an unmet need for widespread, efficient, and routine testing of all biomarkers recommended by clinical guidelines. New testing techniques and technologies can make this an attainable goal. Panel-based sequencing platforms are becoming more accessible, and molecular biomarker analysis of circulating tumor DNA is becoming more common. In this podcast, we discuss the importance of biomarker testing in advanced NSCLC and explore topics such as testing methodologies, effect of biomarker testing on patient outcomes, emerging technologies, and strategies for improving testing rates in the United States. Supplementary file1 (MP4 121301 KB)

Abstract Lung squamous cell carcinoma (LUSC) is associated with high mortality and limited targeted therapies. USP13 is one of the most amplified genes in LUSC, yet its role in lung cancer is largely unknown. Here, we established a novel mouse model of LUSC by overexpressing USP13 on KrasG12D/+; Trp53flox/flox background (KPU). KPU-driven lung squamous tumors faithfully recapitulate key pathohistological, molecular features, and cellular pathways of human LUSC. We found that USP13 altered lineage-determining factors such as NKX2-1 and SOX2 in club cells of the airway and reinforced the fate of club cells to squamous carcinoma development. We showed a strong molecular association between USP13 and c-MYC, leading to the upregulation of squamous programs in murine and human lung cancer cells. Collectively, our data demonstrate that USP13 is a molecular driver of lineage plasticity in club cells and provide mechanistic insight that may have potential implications for the treatment of LUSC. Graphical Abstract

Objective To translate and culturally adapt the Information Needs in Cardiac Rehabilitation (INCR) questionnaire into Korean and perform psychometric validation. Methods The original English version of the INCR, in which patients are asked to rate the importance of 55 topics, was translated into Korean (INCR-K) and culturally adapted. The INCR-K was tested on 101 cardiac rehabilitation (CR) participants at Kangwon National University Hospital and Seoul National University Bundang Hospital in Korea. Structural validity was assessed using principal component analysis, and Cronbach’s alpha of the areas was computed. Criterion validity was assessed by comparing information needs according to CR duration and knowledge sufficiency according to receipt of education. Half of the participants were randomly selected for 1 month of re-testing to assess their responsiveness. Results Following cognitive debriefing, the number of items was reduced to 41 and ratings were added to assess participants’ sufficient knowledge of each item. The INCR-K structure comprised eight areas, each with sufficient internal consistency (Cronbach’s alpha>0.7). Criterion validity was supported by significant differences in mean INCR-K scores based on CR duration and knowledge sufficiency ratings according to receipt of education (p

Background: DNA methylation forms 5-methylcytosine and its regulation in the hippocampus is critical for learning and memory. Indeed, dysregulation of DNA methylation is associated with neurological diseases. Alzheimer’s disease (AD) is the predominant of dementia and a neurodegenerative disorder. Methods: We examined the learning and memory function in 3- and 9-month-old wild-type and 5xfamiliar Alzheimer’s disease (5xFAD) transgenic mice by performing the object recognition memory and Y-maze tests, and identified the hippocampal amyloid beta burden. To investigate the epigenetically regulated genes involved in the development or neuropathology of AD, we performed genome-wide DNA methylation sequencing and RNA sequencing analyses in the hippocampus of 9-month-old wild-type and 5xFAD tg mice. To validate the genes inversely regulated by epigenetics, we confirmed their methylation status and mRNA levels. Results: At 9 months of age, 5xFAD tg mice showed significant cognitive impairment and amyloid-beta plaques in the hippocampus. DNA methylation sequencing identified a total of 13,777 differentially methylated regions, including 4484 of hyper- and 9293 of hypomethylated regions, that are associated with several gene ontology (GO) terms including ‘nervous system development’ and ‘axon guidance’. In RNA sequencing analysis, we confirmed a total of 101 differentially expressed genes, including 52 up- and 49 downregulated genes, associated with GO functions such as ‘positive regulation of synaptic transmission, glutamatergic’ and ‘actin filament organization’. Through further integrated analysis of DNA methylation and RNA sequencing, three epigenetically regulated genes were selected: thymus cell antigen 1, theta (Thy1), myosin VI (Myo6), and filamin A-interacting protein 1-like (Filip1l). The methylation level of Thy1 decreased and its mRNA levels increased, whereas that of Myo6 and Filip1l increased and their mRNA levels decreased. The common functions of these three genes may be associated with the neural cytoskeleton and synaptic plasticity. Conclusions: We suggest that the candidate genes epigenetically play a role in AD-associated neuropathology (i.e., amyloid-beta plaques) and memory deficit by influencing neural structure and synaptic plasticity. Furthermore, counteracting dysregulated epigenetic changes may delay or ameliorate AD onset or symptoms.

Objective To assess the accuracy of recently commercialized wearable devices in heart rate (HR) measurement during cardiopulmonary exercise test (CPX) under gradual increase in exercise intensity, while wearable devices with HR monitors are reported to be less accurate in different exercise intensities. Methods CPX was performed for patients with coronary artery disease (CAD). Twelve lead electrocardiograph (ECG) was the gold standard and Apple watch 7 (AW7), Galaxy watch 4 (GW4) and Bio Patch Mobicare 200 (MC200) were applied for comparison. Paired absolute difference (PAD), mean absolute percentage error (MAPE) and intraclass correlation coefficient (ICC) were evaluated for each device. Results Forty-four participants with CAD were included. All the devices showed MAPE under 2% and ICC above 0.9 in rest, exercise and recovery phases (MC200=0.999, GW4=0.997, AW7=0.998). When comparing exercise and recovery phase, PAD of MC200 and AW7 in recovery phase were significantly bigger than PAD of exercise phase (p

Objective To compare the efficacy of home-based cardiac rehabilitation (HBCR) and center-based cardiac rehabilitation (CBCR) in cardiovascular risk factor management. Methods We performed retrospective review of the electronic medical records of 72 patients who were hospitalized for acute coronary syndrome and participated in a cardiac rehabilitation (CR) program for the first time. The participants were stratified into the HBCR group, receiving educational programs and performing self-exercise at home, and the CBCR group, participating in electrocardiogram monitoring monitoring exercise training in hospital settings. The results of the Lifestyle Questionnaire survey were investigated at baseline, 3 months, and 6 months. Results Both groups showed significant improvements in serum low-density lipoprotein levels, frequency of alcohol consumption, eating habits and psychological status. Moderate-intensity exercise duration and the maximal metabolic equivalents values improved significantly in both groups but slightly more in the CBCR group. However, the number of current smokers increased in both groups, and no significant changes were found in body mass index, serum glycated hemoglobin levels, serum high-density lipoprotein levels, or high-intensity exercise duration. Conclusion Regardless of the CR program type, a patient’s lifestyle can be modified. Therefore, patients should continue participating in any type of CR program.

Abstract Background Cardiac rehabilitation (CR) is an essential component in secondary prevention of cardiovascular diseases. Current guidelines recommend that the program should be comprehensive including multidisciplinary behavioral intervention, not only exercise training. While the utilization of CR is gradually increasing, the comprehensiveness of the program has not been systemically evaluated in Korea. Methods During the year 2020, nation-wide survey was done to evaluate the current status of CR in Korea. Survey was done by web-based structured questionnaire. Survey was requested to 164 hospitals performing percutaneous coronary intervention. Results Among 164 hospitals, 47 (28.7%) hospitals had CR programs. In hospitals with CR, multidisciplinary intervention other than exercise-based program was provided only partially: nutritional counseling (63%), vocational counseling for return to work (39%), stress management (31%), psychological evaluation (18%). Personnel for CR was commonly not dedicated to the program or even absent: (percentage of dedicated, concurrent with other work, absent) physical therapist (59, 41, 0%), nurse (31, 69, 0%), dietician (6, 65, 29%), clinical psychologist (0, 37, 63%). Conclusion Comprehensiveness of CR in Korea is suboptimal and human resource for it is poorly disposed. More awareness of current status by both clinicians and health policy makers is needed and insurance reimbursement for educational program should be improved.

As part of the NCI’s Cancer Center Cessation (C3i) initiative, we initiated, expanded, and maintained an evidence-based tobacco treatment program at the Georgetown Lombardi Comprehensive Cancer Center. We present a quality improvement (QI) assessment of the implementation process and patient-level outcomes. At two hematology/oncology outpatient clinical sites, five oncology-based teams (clinical administrators, clinical staff, pharmacy, information technology, and tobacco treatment staff) developed implementation strategies for opt-out patient assessment and enrollment, centralized tobacco treatment, audit, feedback, and staff training. Among eligible patients (tobacco use in ≤30 days), we assessed demographic, clinical, and tobacco-related characteristics to examine predictors of enrollment (baseline completed), treatment engagement (≥one sessions completed), and self-reported 7-day abstinence (6 months post-enrollment). Across both sites, medical assistants screened 19,344 (82.4%) patients for tobacco use, which identified 1345 (7.0%) current tobacco users, in addition to 213 clinician referrals. Of the 687/1256 (54.7%) eligible patients reached, 301 (43.8%) enrolled, and 199 (29.0%) engaged in treatment, of whom 74.5% were African American and 68% were female. At the larger site, significant multivariate predictors of enrollment included African American race (vs. white/other) and clinician referral (vs. MA assessment). Treatment engagement was predicted by greater nicotine dependence, and abstinence (27.4%) was predicted by greater treatment engagement. In summary, the systematic utilization of multiple oncology-based teams and implementation strategies resulted in the development and maintenance of a high-quality, population-based approach to tobacco treatment. Importantly, these strategies addressed inequities in tobacco treatment, as the program reached and engaged a majority-African-American patient population. Finally, the opt-out patient assessment strategy has been implemented in multiple oncology settings at MedStar Health through the Commission on Cancer’s Just Ask program.

The purpose of this study is to find terms that can give identity to the major and occupation of clinical laboratory technologist (also known as medical technologist). The term clinical pathology includes all branches of pathology, namely anatomical pathology, chemical pathology, hematology, microbiology, and all respective subspecialties. Unfortunately, several countries exclude anatomical pathology from the term clinical pathology, a problem that gets compounded when the title is translated into languages other than English. Clinical pathology (US, UK) is a medical specialty. Similar terms are laboratory medicine (Germany, Poland), medical/clinical biology (France, Netherlands) or clinical analysis (Spain). Depending on the person questioned, medical technology is defined slightly differently by individuals, companies, and institutions. The definition also depends on the language in which the question is asked. Medical technology can be translated to define clinical laboratory technology, allied health sciences, medical equipment, biomedical engineering, and health technology. The terms ‘clinical pathology technology and pathological technology’ are not used in allied health sciences. The names of ‘medical technologyㆍmedical technologist’ can be replaced by ‘biomedical laboratory scienceㆍ biomedical laboratory technologist’ or ‘clinical laboratory analysisㆍclinical laboratory analyst’. In this study, it is proposed to change the name of academic and occupation to ‘medical biologyㆍmedical biology technologist’ that combines the term biomedical.

Background: This study aimed to investigate the efficacy and safety of digital therapeutics (DTx), EASYBREATH, for pulmonary rehabilitation (PR) in patients with chronic respiratory diseases (CRDs). Materials and Methods: This prospective randomized controlled trial was conducted at multiple centers. Participants were randomly allocated 1:1 to the DTx group (DTxG), provided with DTx using EASYBREATH. The DTxG underwent an 8-week PR program with evaluations conducted at baseline, four weeks, and eight weeks. The control group (CG) underwent one PR session and was advised to exercise and undergo the same evaluation. The primary outcome was the change in six-minute walking distance (6MWD) over eight weeks, and secondary outcomes included changes in scores of Modified Medical Research Council (mMRC), chronic obstructive pulmonary disease assessment test (CAT), and St. George’s respiratory questionnaire (SGRQ). Results: The change in 6MWD after eight weeks demonstrated a significant difference between the DTxG and CG (57.68 m vs. 21.71 m, p = 0.0008). The change in mMRC scores (p = 0.0008), CAT scores (p < 0.0001), and total SGRQ scores (p = 0.0003) also showed a significant difference between the groups after eight weeks. Conclusions: EASYBREATH significantly improved exercise capacity, alleviated dyspnea, and enhanced the overall quality of life at eight weeks. EASYBREATH is a highly accessible, time-efficient, and effective treatment option for CRD with high compliance.

Background: RET fusions are driver alterations in cancer and are most commonly found in non-small cell lung cancer and well-differentiated thyroid cancer. However, RET fusion have been reported in other solid tumors. Material and methods: A retrospective analysis of RET+ solid malignancies identified by targeted RNA sequencing and whole transcriptome sequencing of clinical tumor samples performed at Caris Life Science (Phoenix, AZ). Results: As of March 22, 2022, a total of 378 RET+ solid malignancies were identified in 15 different tumor types and carcinoma of unknown primary (CUP) that underwent next-generation RNA sequencing. RET+ NSCLC and RET+ thyroid cancer constituted 66.9% and 11.1% of the RET+ solid malignancies, respectively. RET+ colorectal adenocarcinoma and RET+ breast adenocarcinoma constituted 10.1% and 2.6%, respectively. The estimated frequency of RET fusions within specific tumor types were NSCLC 0.7%, thyroid cancer 3.1%, colorectal cancer 0.2% and breast cancer 0.1%. KIF5B (46.8%) was the most common fusion partner followed by CCDC6 (28.3%) and NCOA4 (13.8%) in RET+ solid tumors. KIF5B-RET was the dominant fusion variant in RET+ NSCLC, NCOA4-RET was the dominant variant in RET+ colorectal carcinoma, and CCDC6-RET was the dominant variant in thyroid cancer. The most common single gene alterations in RET+ tumors were TP53 (34.8%), RASA1 (14.3%) and ARIAD1A (11.6%). RET+ CRC had a high median TMB of 20.0 and were commonly MSI-H. Conclusions: RET fusions were identified in multiple tumor types. With a higher median TMB and commonly MSI-H, RET fusion positive CRC may be a unique molecular subset of CRC.

BackgroundThe incidence of lung cancer in the US has been decreasing but a bigger decline has been observed in men despite similar declines in tobacco use between men and women. Multiple theories have been proposed, including exposure to exogenous estrogens. Our study seeks to understand the relationship between hormone receptors (HR), gender, and the genomic landscape of non-small lung cancer (NSCLC).Methods3,256 NSCLC tumor samples submitted for molecular profiling between 2013-2018 were retrospectively identified and assessed for HR expression. Hormone receptor (HR+) was defined as ≥ 1% nuclear staining of estrogen receptor-alpha (ER-a) or progesterone receptor (PR) by immunohistochemistry. DNA sequencing by NGS included cases sequenced by the Illumina MiSeq hot spot 47 gene panel (n=2753) and Illumina NextSeq 592 gene panel (n=503). An adjusted p-value (q-value)

Summary: Mechanisms underlying distinct specification, commitment, and differentiation phases of cell fate determination remain undefined due to difficulties capturing these processes. Here, we interrogate the activity of ETV2, a transcription factor necessary and sufficient for hematoendothelial differentiation, within isolated fate intermediates. We observe transcriptional upregulation of Etv2 and opening of ETV2-binding sites, indicating new ETV2 binding, in a common cardiac-hematoendothelial progenitor population. Accessible ETV2-binding sites are active at the Etv2 locus but not at other hematoendothelial regulator genes. Hematoendothelial commitment coincides with the activation of a small repertoire of previously accessible ETV2-binding sites at hematoendothelial regulators. Hematoendothelial differentiation accompanies activation of a large repertoire of new ETV2-binding sites and upregulation of hematopoietic and endothelial gene regulatory networks. This work distinguishes specification, commitment, and sublineage differentiation phases of ETV2-dependent transcription and suggests that the shift from ETV2 binding to ETV2-bound enhancer activation, not ETV2 binding to target enhancers, drives hematoendothelial fate commitment.

Abstract Background Cardiac rehabilitation (CR) is a prognostic management strategy to help patients with CVD achieve a good quality of life and lower the rates of recurrence, readmission, and premature death from disease. Globally, cardiac rehabilitation is poorly established in hospitals and communities. Hence, this study aimed to investigate the discrepancies in the perceptions of the need for CR programs and relevant health policies between directors of hospitals and health policy personnel in South Korea to shed light on the status and to establish practically superior and effective strategies to promote CR in South Korea. Methods We sent a questionnaire to 592 public health policy managers and directors of selected hospitals, 132 of whom returned a completed questionnaire (response rate: 22.3%). The participants were categorized into five types of organizations depending on their practice of PCI (Percutaneous Coronary Intervention), establishment of cardiac rehabilitation, director of hospital, and government's policy makers. Differences in the opinions between directors of hospitals that perform/do not perform PCI, directors of hospitals with/without cardiac rehabilitation, and between hospital directors and health policy makers were analyzed. Results Responses about targeting diseases for cardiac rehabilitation, patients’ roles in cardiac rehabilitation, hospitals’ roles in cardiac rehabilitation, and governmental health policies’ roles in cardiac rehabilitation were more positive among hospitals that perform PCI than those that do not. Responses to questions about the effectiveness of cardiac rehabilitation and hospitals’ roles in cardiac rehabilitation tended to be more positive in hospitals with cardiac rehabilitation than in those without. Hospital directors responded more positively to questions about targeting diseases for cardiac rehabilitation and governmental health policies’ roles in cardiac rehabilitation than policy makers, and both hospitals and public organizations provided negative responses to the question about patients’ roles in cardiac rehabilitation. Responses to questions about targeting diseases for cardiac rehabilitation, patients’ roles in cardiac rehabilitation, and governmental health policies’ roles in cardiac rehabilitation were more positive in hospitals that perform PCI than those that do not and public organizations. Conclusions Hospitals must ensure timely referral, provide education, and promote the need for cardiac rehabilitation. In addition, governmental socioeconomic support is needed in a varity of aspects.

Objective To assess the accuracies and validities of popular smart bands for heart rate (HR) measurement in cardiovascular disease (CVD) patients during a graded exercise test (GXT). Methods Seventy-eight patients were randomly assigned to wear two different smart bands out of three possible choices: Samsung Galaxy Fit 2, Xiaomi Mi Band 5, or Partron PWB-250 on each wrist. A 12-lead exercise electrocardiogram (ECG) and patch-type single-lead ECG were used to assess the comparative HR accuracy of the smart bands. The HR was recorded during the GXT using the modified Bruce protocol. Results The concordance correlation coefficients (rc) were calculated to provide a measure of agreement between each device and the ECG. In all conditions, the Mi Band 5 and Galaxy Fit 2’ correlations were rc>0.90, while the PWB-250 correlation was rc=0.58 at rest. When evaluating the accuracy according to the magnitude of HR, all smart bands performed well (rc>0.90) when the HR was below 100 but accuracy tended to decrease with higher HR values. Conclusion This study showed that the three smart bands had a high level of accuracy for HR measurements during low-intensity exercise. However, during moderate-intensity and high-intensity exercise, all the three smart bands performed less accurately. Further studies are needed to find a more optimal smart band for HR measurement that can be used for precise HR monitoring during formal cardiac rehabilitation exercise training, including at high and maximal intensity (Clinical Trial Registration No. cris.nih.go.kr/KCT0007036).

Large-cell neuroendocrine carcinoma (LCNEC) is a rare subtype of non-small-cell lung cancer associated with a poor prognosis. LCNEC is genetically heterogeneous, and studies have revealed distinct molecular subtypes of LCNEC, which may have therapeutic implications. Herein, we present a case of a patient with stage IV LCNEC harboring a KIF5B–RET fusion whose disease responded to the selective RET inhibitor selpercatinib both extra- and intra-cranially, highlighting the importance of comprehensive molecular testing in LCNEC for selection of optimal treatment.

Purpose: Non-small cell lung cancer (NSCLC) is a deadly malignancy that is frequently diagnosed in patients with significant medical comorbidities. When delivering local and regional therapy, an exceedingly narrow therapeutic window is encountered, which often precludes patients from receiving aggressive curative therapy. Radiation therapy advances including particle therapy have been employed in an effort to expand this therapeutic window. Here we report outcomes with the use of proton therapy with curative intent and immunotherapy to treat patients diagnosed with high-risk NSCLC. Methods and Materials: Patients were determined to be high risk if they had severe underlying cardiopulmonary dysfunction, history of prior thoracic radiation therapy, and/or large volume or unfavorable location of disease (eg, bilateral hilar involvement, supraclavicular involvement). As such, patients were determined to be ineligible for conventional x-ray–based radiation therapy and were treated with pencil beam scanning proton beam therapy (PBS-PBT). Patients who demonstrated excess respiratory motion (ie, greater than 1 cm in any dimension noted on the 4-dimensional computed tomography simulation scan) were deemed to be ineligible for PBT. Toxicity was reported using the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Overall survival and progression-free survival were calculated using the Kaplan-Meier method. Results: A total of 29 patients with high-risk NSCLC diagnoses were treated with PBS-PBT. The majority (55%) of patients were defined as high risk due to severe cardiopulmonary dysfunction. Most commonly, patients were treated definitively to a total dose of 6000 cGy (relative biological effectiveness) in 30 fractions with concurrent chemotherapy. Overall, there were a total of 6 acute grade 3 toxicities observed in our cohort. Acute high-grade toxicities included esophagitis (n = 4, 14%), dyspnea (n = 1, 3.5%), and cough (n = 1, 3.5%). No patients developed grade 4 or higher toxicity. The majority of patients went on to receive immunotherapy, and high-grade pneumonitis was rare. Two-year progression-free and overall survival was estimated to be 51% and 67%, respectively. COVID-19 was confirmed or suspected to be responsible for 2 patient deaths during the follow-up period. Conclusions: Radical PBS-PBT treatment delivered in a cohort of patients with high-risk lung cancer with immunotherapy is feasible with careful multidisciplinary evaluation and rigorous follow-up.

Despite numerous studies on cancer treatment, cancer remains a challenging disease to cure, even after decades of research. In recent years, the cancer vaccine has emerged as a promising approach for cancer treatment, offering few unexpected side effects compared to existing therapies. However, the cancer vaccine faces obstacles to commercialization due to its low efficacy. Particularly, the Toll-like receptor (TLR) adjuvant system, specifically the TLR 7/8 agonist, has shown potential for activating Th1 immunity, which stimulates both innate and adaptive immune responses through T cells. In this study, we developed ProLNG-S, a cholesterol-conjugated form of resiquimod (R848), to enhance immune efficacy by stimulating the immune system and reducing toxicity. ProLNG-S was formulated as ProLNG-001, a positively charged liposome, and co-administered with ovalbumin (OVA) protein in the B16-OVA model. ProLNG-001 effectively targeted secondary lymphoid organs, resulting in a robust systemic anti-tumor immune response and tumor-specific T cell activation. Consequently, ProLNG-001 demonstrated potential for preventing tumor progression and improving survival compared to AS01 by enhancing anti-tumor immunity.

Abstract The liner of a CNG pressure vessel is manufactured by a DDI (deep drawing and ironing) process for the cylinder part, which is a continuous process that includes a drawing process to reduce the diameter of the billet and a subsequent ironing process to reduce the thickness of the billet. A tractrix die used in the 1st deep drawing allows the blank to flow smoothly by decreasing the punch load and radial tensile stress occurring in the workpiece. It also increases the draw ratio compared to conventional dies, but it causes forming defects. In this study, a shape coefficient (S c) is proposed for the tractrix die using the blank diameter (D 0), inflow diameter of the workpiece (d i ), and inflow angle of the workpiece ( $$\theta$$ θ ) for design of the tractrix die. The effects of the thickness and inflow angle of the workpiece on wrinkling and folding were investigated through FEA. Also, a discriminant is proposed for the relative radial stress ( $$\tilde{\sigma }$$ σ ~ ) generated during the deep drawing process using the tractirx die and used to predict fracture. Based on the results, the blank thickness, the draw ratio, and the inflow of the workpiece angle in the 1st deep drawing process are suggested, and the number of operations in the DDI process was reduced from 6 to 4. This improves the productivity and reduces the manufacturing cost.

Sotorasib is a KRASG12C inhibitor that recently received approval for use in locally advanced or metastatic KRASG12C-mutated NSCLC. CodeBreaK100, the phase 2 clinical trial leading to the approval of sotorasib, excluded patients with untreated brain metastases; there have been no reports describing efficacy of sotorasib on untreated brain metastases. We present a case of a patient with active untreated brain metastases with resulting disorientation and weakness who has radiographic response and complete resolution of neurologic symptoms with sotorasib. Our case illustrates the intracranial activity of sotorasib, but additional studies are needed to characterize the intracranial response rate and duration of response in these patients.

Abstract In this paper, we study the fragmentation of a heavy quark into a jet near threshold, meaning that final state jet carries most of the energy of the fragmenting heavy quark. Using the heavy quark fragmentation function, we simultaneously resum large logarithms of the jet radius R and 1 − z, where z is the ratio of the jet energy to the initiating heavy quark energy. There are numerically significant corrections to the leading order rate due to this resummation. We also investigate the heavy quark fragmentation to a groomed jet, using the soft drop grooming algorithm as an example. In order to do so, we introduce a collinear-ultrasoft mode sensitive to the grooming region determined by the algorithm’s z cut parameter. This allows us to resum large logarithms of z cut /(1 − z), again leading to large numerical corrections near the endpoint. A nice feature of the analysis of the heavy quark fragmenting to a groomed jet is the heavy quark mass m renders the algorithm infrared finite, allowing a perturbative calculation. We analyze this for E J R ∼ m and E J R » m, where E J is the jet energy. To do the latter case, we introduce an ultracollinear-soft mode, allowing us to resum large logarithms of E J R/m. Finally, as an application we calculate the rate for e + e − collisions to produce a heavy quark jet in the endpoint region, where we show that grooming effects have a sizable contribution near the endpoint.

Corona discharge generates an electrohydrodynamic (EHD) flow and a reactive thrust between electrodes in the air. Although the theory for this thrust between two electrodes has been thoroughly developed, the mechanism responsible for the reactive forces acting on the electrode surfaces is not well understood. Here, we numerically and experimentally investigate these forces and the charges that generate them. The results show that the emitter and collector surface charges deviate from the equality of capacitive charges as the discharge initiates. As the applied voltage increases, the emitter surface charge maintains its initial onset value, while the collector surface charge and the volume charge between the electrodes linearly increase. In the same manner, the emitter and collector surface forces deviate from the equilibrium of action and reaction as the discharge initiates. As the circuit current increases, the emitter surface force maintains its initial onset value, while the collector surface force and the thrust linearly increase. In particular, we demonstrate an unconventional thrust-measuring method by installing a windshield in the rear of the thruster. The force exerted on the windshield is equal to a good approximation of the pure EHD thrust. Also, the difference between this force and the thrust measured without the windshield can be taken as the approximate drag force acting on the electrodes.

Osimertinib, a third-generation EGFR tyrosine kinase inhibitor, is the frontline standard in the treatment of metastatic EGFR-mutant NSCLC. Although osimertinib is effective, disease progression occurs in virtually all patients, mediated by a heterogeneous array of resistance mechanisms. Activation of the MET signaling pathway by means of amplification has been implicated in resistance to osimertinib, but activation caused by point mutations in MET has not been well described.Here, we present the case of a 65-year-old female with metastatic EGFR-mutant NSCLC whose disease progressed on osimertinib owing to emergence of MET Y1003N mutation. She subsequently received capmatinib in combination with osimertinib and achieved a partial response. This case illustrates a potential role for dual EGFR/MET inhibition in EGFR-mutated NSCLC with resistance driven by activating MET mutations.

Introduction: Genomic alterations in the juxtamembrane exon 14 splice sites in NSCLC lead to increased MET stability and oncogenesis. We present the largest cohort study of MET Exon 14 (METex14) using whole transcriptome sequencing. Methods: A total of 21,582 NSCLC tumor samples underwent complete genomic profiling with next-generation sequencing of DNA (592 Gene Panel, NextSeq, whole exome sequencing, NovaSeq) and RNA (NovaSeq, whole transcriptome sequencing). Clinicopathologic information including programmed death-ligand 1 and tumor mutational burden were collected and RNA expression for mutation subtypes and MET amplification were quantified. Immunogenic signatures and potential pathways of invasion were characterized using single-sample gene set enrichment analysis and mRNA gene signatures. Results: A total of 533tumors (2.47%) with METex14 were identified. The most common alterations were point mutations (49.5%) at donor splice sites. Most alterations translated to increased MET expression, with MET co-amplification resulting in synergistic increase in expression (q < 0.05). Common coalterations were amplifications of MDM2 (19.0% versus 1.8% wild-type [WT]), HMGA2 (13.2% versus 0.98% WT), and CDK4 (10.0% versus 1.5% WT) (q < 0.05). High programmed death-ligand 1 > 50% (52.5% versus 27.3% WT, q < 0.0001) and lower proportion of high tumor mutational burden (>10 mutations per megabase, 8.3% versus 36.7% WT, p < 0.0001) were associated with METex14, which were also enriched in both immunogenic signatures and immunosuppressive checkpoints. Pathways associated with METex14 included angiogenesis and apical junction pathways (q < 0.05). Conclusions: METex14 splicing alterations and MET co-amplification translated to higher and synergistic MET expression at the transcriptomic level. High frequencies of MDM2 and CDK4 co-amplifications and association with multiple immunosuppressive checkpoints and angiogenic pathways provide insight into potential actionable targets for combination strategies in METex14 NSCLC.

Objective To examine whether patients who participated in a cardiac rehabilitation (CR) program after hospitalization for acute coronary syndrome maintained cardiorespiratory fitness (CRF) in the community. Methods We conducted a retrospective study including 78 patients who underwent percutaneous coronary intervention or coronary artery bypass graft surgery at our hospital’s cardiovascular center and participated in a CR program and a 5-year follow-up evaluation. Patients were divided into a center-based CR (CBCR) group, participating in an electrocardiography-monitored exercise training in a hospital setting, and a home-based CR (HBCR) group, receiving aerobic exercise training and performed self-exercise at home. Results No significant differences were found between groups (p>0.05), except the proportion of non-smokers (CBCR 59.5% vs. HBCR 31.7%; p=0.01). In both groups, the maximal oxygen consumption (VO2max) increased significantly during the first 12 weeks of follow-up and remained at a steady state for the first year, but it decreased after the 1-year follow-up. Particularly, VO2max at 5 years decreased below the baseline value in the HBCR group. In the low CRF group, the CRF level significantly improved at 12 weeks, peaked at 1 year, and was still significantly different from the baseline value after 5 years. The high CRF group did not show any significant increase over time relative to the baseline value, but most patients in the high CRF group maintained relatively appropriate CRF levels after 5 years. Conclusion Continuous support should be provided to patients to maintain optimal CRF levels after completing a CR program.

Abstract In soft-collinear effective theory, we analyze the structure of rapidity divergence due to the collinear and soft modes residing in disparate phase spaces. The idea of an effective theory is applied to a system of collinear modes with large rapidity and soft modes with small rapidity. The large-rapidity (collinear) modes are integrated out to obtain the effective theory for the small-rapidity (soft) modes. The full SCET with the collinear and soft modes should be matched onto the soft theory at the rapidity boundary, and the matching procedure becomes exactly the zero-bin subtraction. The large-rapidity region is out of reach for the soft mode, which results in the rapidity divergence. The rapidity divergence in the collinear sector comes from the zero-bin subtraction, which ensures the cancellation of the rapidity divergences from the soft and collinear sectors. In order to treat the rapidity divergence, we construct the rapidity regulators consistently for all the modes. They are generalized by assigning independent rapidity scales for different collinear directions. The soft regulator incorporates the correct directional dependence when the innate collinear directions are not back-to-back, which is discussed in the N-jet operator. As an application, we consider the Sudakov form factor for the back-to-back collinear current and the soft-collinear current, where the soft rapidity regulator for a soft quark is developed. We extend the analysis to the boosted heavy quark sector and exploit the delicacy with the presence of the heavy quark mass. We present the resummed results of large logarithms in the form factors for various currents with the light and the heavy quarks, employing the renormalization group evolution on the renormalization and the rapidity scales.

The elliptical disc is a specific characteristic of a triple offset butterfly valve (TOBV), but the structure of the elliptical disc leads to a non-uniform distribution of contact at the closing position with non-uniform wear. On the other hand, the continuous processing of elliptical sections to finish the entire disc contour is expensive compared to the processing of a circular section. In the present study, to improve the above disadvantages of an elliptical disc, an elliptic cone function was established to describe the quadruple butterfly valve (QOBV) disc shape, which has a circular section disc. In addition, some designs of a fixed thickness (7 mm) laminated seal for good sealing were proved. Sealing performance simulations were carried out using the thermal–structural coupling analysis. The best design of the QOBV showed that the maximum contact pressure was 37.2% lower than the TOBV using the seven-way laminated seal layers (thickness of A240–316 stainless and graphite was 1.3 mm and 0.6 mm, respectively). Compared to TOBV, the QOBV disc operation during the opening and closing process was faster and smoother. The disc can be applied widely to various industrial fields, engine exhaust systems, and turbine and power plants under severe environments.

Objective We conducted a systematic review and meta-analysis to analyze the effects of cardiac rehabilitation (CR) on post-discharge prognoses of patients with acute myocardial infarction (AMI). Methods A literature search was conducted through four international medical and two Korean databases. Primary outcomes for the effectiveness of CR included all-cause mortality, cardiovascular mortality, recurrence, revascularization, major adverse cardiovascular event, major adverse cardiocerebrovascular event, and readmission. We summarized and analyzed results of studies about CR for AMI, including not only randomized controlled trials (RCTs) but also non-RCTs. We calculated the effect size separately by the study type. Results Fourteen articles were finally selected. Of these, two articles were RCTs, while 12 were non-RCTs. In RCTs, the overall mortality rate was lower in the group that participated in CR than that in the conventional care group by 28% (relative risk=0.72; 95% confidence interval, 0.34–1.57). Among non-RCTs, CR participation significantly decreased the overall risk of mortality. Moreover, the rates of recurrence and major adverse cardiovascular events were lower in the group that participated in CR compared to those in the non-CR group. Conclusion The meta-analysis shows that CR reduces the risk of re-hospitalization and all-cause mortality after AMI, compared to no participation in CR. This outcome was seen in RCTs as well as in non-RCTs. More studies are necessary for concrete conclusions about the beneficial effects of CR after AMI in various settings.

Abstract Rotation of MO6 (M = transition metal) octahedra is a key determinant of the physical properties of perovskite materials. Therefore, tuning physical properties, one of the most important goals in condensed matter research, may be accomplished by controlling octahedral rotation (OR). In this study, it is demonstrated that OR can be driven by an electric field in Sr2RuO4. Rotated octahedra in the surface layer of Sr2RuO4 are restored to the unrotated bulk structure upon dosing the surface with K. Theoretical investigation shows that OR in Sr2RuO4 originates from the surface electric field, which can be tuned via the screening effect of the overlaid K layer. This work establishes not only that variation in the OR angle can be induced by an electric field, but also provides a way to control OR, which is an important step toward in situ control of the physical properties of perovskite oxides.

Abstract Background The abscopal effect was described as early as the 1950s, when untreated tumors demonstrated a response after radiation therapy was delivered to an untreated, distant site. The mechanisms underlying this global response to otherwise localized therapy remain unknown, though there is increasing evidence that increased antigen expression following ablative radiotherapy may play a role. Case presentation We report a case of a 69-year-old African American woman with a history of metastatic typical pulmonary carcinoid with multiple lung nodules who had a significant decrease in size of an untreated left upper lobe nodule after stereotactic body radiation therapy to an oligoprogressive left lower lobe lesion. Conclusions To our knowledge, this report describes the first case of an abscopal effect in a typical pulmonary carcinoid. Further research is needed regarding the mechanisms responsible for this finding and the role of combining radiation therapy and cancer immunotherapy in patients with pulmonary carcinoid tumors.

Abstracts Background Patients with chronic viral infections including human immunodeficiency virus (HIV), hepatitis B (HBV) and hepatitis C (HCV) are at increased risk of developing malignancies. The safety and efficacy of ICI therapy in patients with both cancer and chronic viral infections is not well established as most clinical trials of ICIs excluded these patient populations. Methods We performed a retrospective analysis of patients with advanced-stage cancers and HIV, HBV, or HCV infection treated with ICI therapy at 5 MedStar Health hospitals from January 2011 to April 2018. Results We identified 50 patients including 16 HIV, 29 HBV/HCV, and 5 with concurrent HIV and either HBV or HCV. In the HIV cohort (n = 21), any grade immune-related adverse events (irAEs) were 24% with grade ≥ 3 irAEs 14%. Among 5 patients with matched pre/post-treatment results, no significant changes in HIV viral load and CD4+ T-cell counts were observed. RECIST confirmed (n = 18) overall response rate (ORR) was 28% with 2 complete responses (CR) and 3 partial responses (PR). Responders included 2 patients with low baseline CD4+ T-cell counts (40 and 77 cells/ul, respectively). In the HBV/HCV cohort (n = 34), any grade irAEs were 44% with grade ≥ 3 irAEs 29%. RECIST confirmed ORR was 21% (6 PR). Among the 6 patients with known pre/post-treatment viral titers (2 HCV and 4 HBV), there was no evidence of viral reactivation. Conclusions Our retrospective series is one of the largest case series to report clinical outcomes among HIV, HBV and HCV patients treated with ICI therapy. Toxicity and efficacy rates were similar to those observed in patients without chronic viral infections. Viral reactivation was not observed. Tumor responses occurred in HIV patients with low CD4 T-cell counts. While prospective studies are needed to validate above findings, these data support not excluding such patients from ICI–based clinical trials or treatment.

BackgroundOsimertinib is an effective first-line therapy option for EGFR-mutant NSCLC, but virtually all patients develop resistance. CRIPTO, through Src activation, has been implicated in resistance to EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy. Dasatinib, a Src inhibitor, has shown preclinical synergy with EGFR-TKI therapy.MethodThis is a single-arm phase I/II trial of osimertinib and dasatinib in TKI-naïve advanced EGFR-mutant NSCLC (NCT02954523). A 3 + 3 design was used in the phase I to establish the recommended phase II dose (RP2D). Osimertinib 80 mg QD was combined with dasatinib 70 mg BID (DL2), 50 mg BID (DL1), 70 mg QD (DL-1), and 50 mg QD (DL-2).ResultsTen patients (DL2: 3, DL1: 6, DL -1: 1) were enrolled. 3 (50%) of 6 patients at DL1 experienced a DLT (grade 3 headaches/body pain, neutropenia, rash, one each). Common treatment-related adverse events included pleural effusion (n=10), diarrhea (n=8), rash (n=7), transaminitis (n=7), thrombocytopenia (n=7), and neutropenia (n=7). While the MTD was not determined by protocol-defined DLT criteria, DL-2 was chosen as the RP2D, considering overall tolerability. Nine (90%) patients had a PR, including 1 unconfirmed PR. Median PFS was 19.4 months and median OS 36.1 months. The trial was closed to accrual prematurely due to slow accrual after the approval of osimertinib as first-line therapy.ConclusionsThe combination of dasatinib and osimertinib demonstrated anticancer activity. The treatment was limited by chronic toxicities mainly attributed to dasatinib. To improve the safety and tolerability of Src and EGFR co-inhibition, Src inhibitors with a more favorable safety profile should be utilized in future studies.Clinical Trial Registrationhttps://clinicaltrials.gov/ct2/show/NCT02954523

Cytokine release syndrome (CRS) is a well-described immune-related adverse event following chimeric antigen receptor T-cell therapy, but has rarely been reported following anti-programmed death ligand-1 therapy. We report the case of a 55-year-old man with metastatic lung adenocarcinoma who presented with fever, chills and hypotension. Initial labs were notable for highly elevated serum ferritin levels and mildly elevated triglyceride levels. He was ultimately diagnosed with pembrolizumab-induced CRS complicated by multiorgan failure. The patient was treated with steroids and tocilizumab with normalization of inflammatory markers and resolution of renal failure. This case not only highlights the importance of considering CRS in patients who have developed multiorgan failure after immune checkpoint inhibitor therapy, but also demonstrates clinical similarities between CRS and other hyperinflammatory states such as hemophagocytic lymphohistiocytosis.

Osimertinib, a third-generation EGFR tyrosine kinase inhibitor, is the preferred frontline therapy for EGFR-mutant advanced NSCLC. However, despite its high initial response rates, multiple EGFR-independent mechanisms of resistance have been reported in patients receiving osimertinib. One such mechanism is the emergence of acquired, targetable oncogenic fusion events. It has been documented in other case reports that combination therapies can be efficacious in these scenarios. In our case report, we present a patient with EGFR-mutant advanced NSCLC who developed an acquired EML4-ALK rearrangement mediating resistance to osimertinib, which was overcome by using a combination of osimertinib with the ALK tyrosine kinase inhibitor alectinib.

Abstract As energy crisis and environment pollution all around the world threaten the widespread use of fossil fuels, compressed natural gas (CNG) vehicles are explored as an alternative to the conventional gasoline powered vehicles. Because of the limited space available for the car, the composite pressure vessel (Type II) has been applied to the CNG vehicles to reach large capacity and weight lightening vehicles. High pressure vessel (Type II) is composed of a composite layer and a metal liner. The metal liner is formed by the deep drawing and ironing (D.D.I.) process, which is a complex process of deep drawing and ironing. The cylinder part is reinforced by composite layer wrapped through the filament winding process and is bonded to the liner by the curing process. In this study, an integrated design method was presented by establishing the techniques for FE analysis of entire processes (D.D.I., filament winding and curing processes) to manufacture the CNG composite pressure vessel (Type II). Dimensions of the dies and the punches of the 1st (cup drawing), 2nd (redrawing-ironing 1-ironing 2) and 3rd (redrawing-ironing) stages were calculated theoretically, and shape of tractrix die to be satisfied with the minimum forming load was suggested for life improvement and manufacturing costs in the D.D.I. process. Thickness of the composite material was determined in the filament winding process, finally, conditions of the curing process (number of heating stage, curing temperature, heating rate and time) were proposed to reinforce adhesive strength between the composite layers.

Background: Cardiac rehabilitation (CR) is a clinically-effective but complex model of care. The purpose of this study was to characterize the nature of CR programs around the world, in relation to guideline recommendations, and compare this by World Health Organization (WHO) region. Methods: In this cross-sectional study, a piloted survey was administered online to CR programs globally. Cardiac associations and local champions facilitated program identification. Quality (benchmark of ≥75% of programs in a given country meeting each of 20 indicators) was ranked. Results were compared by WHO region using generalized linear mixed models. Findings: 111/203 (54.7%) countries in the world offer CR; data were collected in 93 (83.8%; N = 1082 surveys, 32.1% program response rate). The most commonly-accepted indications were: myocardial infarction (n = 832, 97.4%), percutaneous coronary intervention (n = 820, 96.1%; 0.10), and coronary artery bypass surgery (n = 817, 95.8%). Most programs were led by physicians (n = 680; 69.1%). The most common CR providers (mean = 5.9 ± 2.8/program) were: nurses (n = 816, 88.1%; low in Africa, p

Background: Despite the epidemic of cardiovascular disease and the benefits of cardiac rehabilitation (CR), availability is known to be insufficient, although this is not quantified. This study ascertained CR availability, volumes and its drivers, and density. Methods: A survey was administered to CR programs globally. Cardiac associations and local champions facilitated program identification. Factors associated with volumes were assessed using generalized linear mixed models, and compared by World Health Organization region. Density (i.e. annual ischemic heart disease [IHD] incidence estimate from Global Burden of Disease study divided by national CR capacity) was computed. Findings: CR was available in 111/203 (54.7%) countries; data were collected in 93 (83.8% country response; N = 1082 surveys, 32.1% program response rate). Availability by region ranged from 80.7% of countries in Europe, to 17.0% in Africa (p

Background: Though clinical practice guidelines (CPGs) for cardiac rehabilitation (CR) are an effective and widely used treatment method worldwide, they are as yet not widely accepted in Korea. Given that cardiovascular disease is the second leading cause of death in Korea, it is urgent that CR programs be developed. In 2008, the Government of Korea implemented CR programs at 11 university hospitals as part of its Regional Cardio-Cerebrovascular Center Project, and 3 additional medical facilities will be added in 2019. In addition, owing to the promotion of CR nationwide and the introduction of CR insurance benefits, 40 medical institutions nationwide have begun CR programs even as a growing number of medical institutions are preparing to offer CR. The purpose of this research was to develop evidence-based CPGs to support CR implementation in Korea. Methods: This study is based on an analysis of CPGs elsewhere in the world, an extensive literature search, a systematic analysis of multiple randomized control trials, and a CPG management, development, and assessment committee comprised of 33 authors—primarily rehabilitation specialists, cardiologists, and thoracic surgeons in 21 university hospitals and 2 general hospitals. Twelve consultants, primarily rehabilitation, sports medicine, and preventive medicine specialists, CPG experts, nurses, physical therapists, clinical nutritionists, and library and information experts participated in the research and development of these CPGs. After the draft guidelines were developed, 3 rounds of public hearings were held with staff members from relevant academic societies and stakeholders, after which the guidelines were further reviewed and modified. Results: CR involves a more cost-effective use of healthcare resources relative to that of general treatments, and the exercise component of CR lowers cardiovascular mortality and readmission rates, regardless of the type of coronary heart disease and type and setting of CR. Conclusion: Individualized CR programs should be considered together with various factors, including differences in heart function and lifestyle, and doing so will boost participation and adherence with the CR program, ultimately meeting the final goals of the program, namely reducing the recurrence of myocardial infarction and mortality rates.

This paper presents an efficient home-based cardiac rehabilitation (CR) exercise system for patient-healthcare provider interaction in cardiac management. The proposed system consists of a wearable device, a smartphone application, and a medical station. A CR specialist prescribes CR exercise for a patient through a medical station. The prescription information is sent to a patient's smartphone application with Internet's hypertext transfer protocol. The information is further transferred to a patient's wearable device via Bluetooth communication. A patient performs home-based CR exercise with the worn wearable device that measures instantaneous heart rates (HRs) accurately even during intensive physical exercise. During the CR exercise, the wearable device recommends appropriate exercise intensity in real time based on the prescribed target HR zone and the measured instantaneous HRs. Furthermore, the wearable device informs the current exercise stage (resting, walking, or running), allowing home-based CR exercise without the help of a medical staff. Upon completion of the CR exercise, exercise records are sent to a smartphone application so that a patient can monitor his or her own exercise records. Exercise records are also sent to the medical station where a CR specialist can monitor these records and provide new exercise prescription. In this paper, we have implemented and demonstrated the full functionality of the overall home-based CR exercise system consisting of a wearable device, a smartphone application, and a medical station. Moreover, we have verified the overall operation of the system and that the proposed system can be an efficient CR exercise tool for remotely sharing CR exercise prescription and exercise records between a patient and a healthcare provider.

Miniaturized implantable devices play a crucial role in neural interfaces by monitoring and modulating neural activities on the peripheral and central nervous systems. Research efforts toward a compact wireless closed-loop system stimulating the nerve automatically according to the user's condition have been maintained. These systems have several advantages over open-loop stimulation systems such as reduction in both power consumption and side effects of continuous stimulation. Furthermore, a compact and wireless device consuming low energy alleviates foreign body reactions and risk of frequent surgical operations. Unfortunately, however, the miniaturized closed-loop neural interface system induces several hardware design challenges such as neural activity recording with severe stimulation artifact, real-time stimulation artifact removal, and energy-efficient wireless power delivery. Here, we will review recent approaches toward the miniaturized closed-loop neural interface system with integrated circuit (IC) techniques.

The root of Dipsacus asperoides C. Y. Cheng et T. M. Ai is traditionally used as an analgesic and anti-inflammatory agent to treat pain, rheumatoid arthritis, and bone fractures. However, neither its effects on osteoarthritis (OA) nor its effects on the arthritic cartilage tissue transcriptome have not been fully investigated. In this study, we used a rat model of monosodium iodoacetate- (MIA-) induced OA to investigate the therapeutic effects of a Dipsacus asperoides ethanolic extract (DAE, 200 mg/kg for 21 days). The study first assessed joint diameter, micro-CT scans, and histopathological analysis and then conducted gene expression profiling using RNA sequencing in articular cartilage tissue. We found that DAE treatment ameliorates OA disease phenotypes; it reduced the knee joint diameter and prevented changes in the structural and histological features of the joint, thereby showing that DAE has a protective effect against OA. Based on the results of gene expression profiling and subsequent pathway analysis, we found that several canonical pathways were linked to DAE treatment, including WNT/β-catenin signaling. Taken together, the present results suggest molecular mechanism, involving gene expression changes, by which DAE has a protective effect in a rat model of MIA-induced OA.

Introduction: The clinical successes seen with anti–programmed cell death protein 1/programmed death-ligand 1 (anti–PD-[L]1) agents have galvanized the field of immuno-oncology. We evaluated the landscape and trends in immunotherapy trials involving the PD-(L)1 axis in intrathoracic tumors. Methods: We identified clinical trials involving anti–PD-(L)1 agents on the ClinicalTrials.gov registry through November 13, 2020 for NSCLC, SCLC, mesothelioma, and thymic epithelial tumor. Clinical trials were indexed according to monotherapy versus combination approaches, PD-(L)1 agents under investigation, clinical settings, trial start date, and partner drug(s). We assessed redundancy among the clinical trials. Results: We found 686 clinical trials investigating anti–PD-(L)1 agents for intrathoracic tumors (540 trials in NSCLC, 96 in SCLC, 38 in mesothelioma, and 12 in thymic epithelial tumor). A total of 23 PD-(L)1 inhibitors are undergoing clinical development. A total of 81% of trials assess combination treatment. The number of clinical trials has been growing exponentially in the past decade. PD-(L)1 blockade was frequently combined with chemotherapy or immunomodulatory therapy. Various strategies are in development to overcome resistance to PD-(L)1 blockade in metastatic NSCLC. PD-(L)1 blockade is also increasingly evaluated in neoadjuvant and adjuvant settings. After the U.S. Food and Drug Administration’s approval of an anti–PD-(L)1 agent for a specific indication, 14 trials were launched thereafter, which continued to randomize patients to treatments that were inferior to the best available therapy. Conclusions: The number of clinical trials investigating anti–PD-(L)1 agents in intrathoracic tumors has experienced a steep increase over the past decade with a notable upward trend for combination trials. To reduce duplicative research efforts and accelerate the development of effective immunotherapeutics, improved coordination among key stakeholders and the adoption of innovative trial designs will be vital.

Cancer is considered to be an independent risk factor for severe illness and higher mortality in patients with coronavirus disease 2019 (COVID-19). These adverse outcomes have been suspected to be more severe in patients with lung cancer. The objective of this systematic review and meta-analysis is to outline patient characteristics, challenges in diagnosis and treatment, and outcomes of patients with lung cancer with COVID-19. A comprehensive search was conducted using EMBASE and PubMed databases using the terms “COVID” and “cancer.” Studies that reported clinical characteristics or outcomes of patients with lung cancer with COVID-19 were then systematically identified. Meta-analysis for COVID-19 related mortality associated with lung cancer compared with other cancer types was conducted. The results were reported as OR and confidence intervals using the mixed-effects logistic regression model. The most frequently reported clinical findings in patients with lung cancer with COVID-19 were fever and cough, with 68% and 61%, respectively. Laboratory and radiographic findings were consistent with broadly reported data. The meta-analysis noted a statistically significant increase in mortality rate in patients with lung cancer compared with other patients with cancer, with an OR of 1.62 (95% confidence interval: 1.06–2.48). Patients with lung cancer with COVID-19 also reflected greater severity of illness and higher rates of intensive care unit admissions and mechanical ventilation. COVID-19 in patients with lung cancer is associated with severe disease and increased mortality relative to patients with other malignancies and the general population. There is conflicting evidence on the effect of specific lung cancer treatments on outcomes. Until more definitive data is available, lung cancer–directed treatment should be continued or restarted as early as possible in mild to moderate cases to prevent worsening and cancer-related mortality.

Scarcity of fossil fuels and their emissions of fossil fuel pollutants, such as carbon dioxide, into the atmosphere, and the resulting consequences, have led energy policymakers to look for alternative renewable and clean energy sources. The use of animal wastes is one of the very promising renewable energy alternatives paving the way for a more sustainable energy network. Animal manure produced by livestock farms has a moisture content of about 80%, and such livestock manure is dehydrated to a moisture content of 20–25% and solidified to be used as biomass and fuel for thermal power plants. Previous studies on manure dryers have been concentrated on convection-type dryers, but this type of dryer has the disadvantage of inadequate processing capacity per hour because it cannot agitate manure. In this study, to deal with the drawbacks of conventional livestock manure drying methods, a screw-type dryer was proposed. CFD analysis of the dryer was performed by selecting the viscosity of livestock manure and design parameters of the screw using Ansys Workbench. Through the response surface method, optimal design of the screw shape for the improvement of drying efficiency and smooth discharge of residual manure was carried out.

Background Lutathera is a 177Lutetium-labeled somatostatin analog approved for the treatment of gastroenteropancreatic neuroendocrine tumors (NETs). Somatostatin receptors are expressed in small cell lung cancer (SCLC). Nivolumab, an anti-PD-1 antibody, may act synergistically with lutathera to generate antitumor immunity. We conducted a phase I study of lutathera plus nivolumab in patients with advanced NETs of the lung.Methods Patients with relapsed/refractory extensive-stage SCLC (ES-SCLC), non-progressing ES-SCLC after first-line platinum-based chemotherapy, or advanced grade I-II pulmonary NETs were eligible. The primary objective was to determine the recommended phase 2 dose (RP2D). The phase I portion followed a standard 3+3 design, assessing two dose levels (dose level 1: lutathera 3.7 GBq every 8 weeks for four doses with nivolumab 240 mg every 2 weeks; dose level 2: lutathera 7.4 GBq every 8 weeks for four doses with nivolumab 240 mg every 2 weeks).Results Nine patients were enrolled (six ES-SCLC, two pulmonary atypical carcinoid, one high-grade pulmonary neuroendocrine carcinoma). No dose-limiting toxicities (DLTs) were observed at dose level 1. At dose level 2, one patient with refractory ES-SCLC developed a DLT (grade 3 rash). The most common treatment-related adverse events (TRAEs) were lymphopenia (n=7), thrombocytopenia (n=4), anemia (n=3), and nausea (n=3). The most common grade 3 TRAE was lymphopenia (n=4). Among the seven patients with measurable disease, one patient with ES-SCLC had a partial response. Two patients with pulmonary atypical carcinoid had stable disease lasting 6 months. The RP2D was dose level 2.Conclusions Lutathera plus nivolumab was well tolerated and showed signs of antitumor activity. This combination warrants further exploration.Trial registration number NCT03325816