Exploration of helpful elements contributing to engage in physical activity in patients with cancer.

PURPOSE: Although there are many reported benefits of physical activity for patients with cancer (e.g., improving quality of life), many patients with cancer do not meet the recommendations of physical activity guidelines. The amount of physical activity declines after diagnosis of cancer. This study aimed to clarify the elements that contribute engagement in regular moderate-or-higher-level intensity of physical activity (MHPA), based on the Health Action Process Approach (HAPA), among patients with cancer. METHODS: Two web surveys were conducted among cancer outpatients, asking them to respond to a questionnaire. Participants provided information regarding their demographics, physical activity, purpose, advantages, disadvantages, barriers, triggers, and need for support for regular MHPA. RESULTS: Categories were obtained for purposes, advantages, disadvantages, barriers, triggers, and support needs for regular MHPA. For example, the support they considered necessary to regularly engage in MHPA were developed 9 categories, such as Improving the environment, Support for the implementation of PA (interpersonal), and Reducing the burden. Women and younger patients provided more statements about reducing their burden; younger patients also mentioned on improving the environment more among those who did not engage in MHPA. Additionally, patients with cancer who provided statements about interpersonal support reported higher barriers to physical activity. CONCLUSIONS: These findings will contribute to the development of a scale to measure the components of the HAPA on physical activity in patients with cancer. In addition, it will help develop a support system that promotes engagement in regular MHPA.

Deconstructing the masculinized assumption of the medical profession: narratives of Japanese physician fathers.

BACKGROUND: Gender studies in the medical profession have revealed gender biases associated with being a doctor, a profession often regarded as more suitable for men. The path to gender equality inevitably involves deconstructing this masculinized assumption. Despite the decades-long expectation that ikumen-men who actively participate in childcare in Japan-would contribute to a change toward gender equality, Japanese society is still male dominated, and women suffer from a large gender gap. With the aim of exploring implicit gendered assumptions concerning being a caregiver and a doctor, the authors focused on the experience of individuals juggling the binary roles of a professional and a caregiver. METHODS: The authors conducted subjectivist inductive research, recruited ten Japanese physician fathers through purposive sampling, and collected data through one-to-one semi-structured interviews between October 2017 and December 2018. The authors recorded and transcribed the narrative data, and extracted themes and representative narratives. RESULTS: The study identified three themes about the reproduction and potential change of the gender gap: maintaining gendered assumptions of the medical profession without experiencing conflict, maintaining gendered assumptions of the medical profession while experiencing conflict, and deconstructing gendered assumptions of the medical profession through conflict. The authors found that these negotiations interplayed with the gendered division of labor between male doctors and their wives as well as the patriarchal family structure. CONCLUSIONS: The study revealed how gendered assumptions of the medical profession, as well as gender stereotypes and gendered division of household labor, were reproduced in the course of male doctors' negotiations when they became fathers. For male doctors to question their unconscious gender bias, the authors emphasize the importance of men gaining knowledge about gender stereotypes, and propose that educators create such opportunities. Moreover, the authors assert that increasing doctors' awareness of how masculinized assumptions implicitly interact with ideas of being a doctor-an aspect rarely discussed among medical professionals-is crucial for deconstructing the gendered normativity in the medical field.

Perception of native and non-native phonemic contrasts in children with autistic spectrum disorder: effects of speaker variability.

The current study investigated speech perception in children with ASD by directly comparing discrimination accuracy of phonemic contrasts in the native and non-native languages. The effect of speaker variability on phoneme perception was also examined. We also explored the relation between language impairment and accuracy in phoneme discrimination in children with ASD. Significant differences in performance were found between the ASD and TD groups on discrimination of the native phonemic contrasts. By contrast, no difference was found between the two groups on discrimination of the non-native phonemic contrasts. Further subgroup analysis revealed that the ALN group (ASD without language delay or impairment) showed significantly higher discrimination accuracy for the native syllable contrasts than the non-native counterpart. No significant difference was found in the discrimination accuracy between the native and non-native phonemic contrasts in the ALD group (ASD with language delay or impairment). The effect of speaker viability on phoneme discrimination was observed in the TD group but not in the ASD subgroups. Nonverbal reasoning ability was highly related to discrimination accuracy of both the native and non-native phonemic contrasts in children with ASD. The results of the present study suggest that speech perception in children with ASD is not as attuned to their native language as in their TD peers. Our findings also indicate that language delay or impairment is related to difficulty in perception of native phonemes in children with ASD.

Patients' Preferences for Attributes of Molecular Targeting Therapies for Advanced Non-Small Cell Lung Cancer with EGFR Mutations in Japan-A Discrete-Choice Experiment.

AIM: This study aims to evaluate Japanese patients' preferences in first-line therapy choice for advanced non-small cell lung cancer(NSCLC)with epidermal growth factor receptor(EGFR)mutations. METHODS: A cross-sectional discrete-choice experiment was conducted on advanced NSCLC patients in Japan. Participants completed the online questionnaire that included different levels of 5 treatment attributes: time to disease progression, chance of rash, next therapy option, frequency of health care visits and administration route. The primary analysis estimated the relative attribute importance. The preferences of EGFR mutation-positive patients were compared with those of EGFR mutation-negative/unknown patients to observe whether preference differs by mutation status. RESULTS: A total of 158 participants completed the survey. The analysis on the overall study population revealed next therapy option(mean relative attribute importance[SD]: 39.30 [17.07])as the most important attribute, followed by time to disease progression(25.52[10.51]), chance of rash(21.58 [11.74]), with administration route(7.63[6.99])and frequency of health care visits(5.96[3.40])the least preferred. The results in the subgroups by EGFR mutation status were similar. CONCLUSION: Next therapy option is the major influencing factor for treatment choice of molecular targeting therapy among advanced NSCLC patients in Japan, emphasizing the importance of communicating the next treatment options to patients at the time of their first treatment.

Spatial Warped Gaussian Processes: Estimation and Efficient Field Reconstruction.

A class of models for non-Gaussian spatial random fields is explored for spatial field reconstruction in environmental and sensor network monitoring. The family of models explored utilises a class of transformation functions known as Tukey g-and-h transformations to create a family of warped spatial Gaussian process models which can support various desirable features such as flexible marginal distributions, which can be skewed, leptokurtic and/or heavy-tailed. The resulting model is widely applicable in a range of spatial field reconstruction applications. To utilise the model in applications in practice, it is important to carefully characterise the statistical properties of the Tukey g-and-h random fields. In this work, we study both the properties of the resulting warped Gaussian processes as well as using the characterising statistical properties of the warped processes to obtain flexible spatial field reconstructions. In this regard we derive five different estimators for various important quantities often considered in spatial field reconstruction problems. These include the multi-point Minimum Mean Squared Error (MMSE) estimators, the multi-point Maximum A-Posteriori (MAP) estimators, an efficient class of multi-point linear estimators based on the Spatial-Best Linear Unbiased (S-BLUE) estimators, and two multi-point threshold exceedance based estimators, namely the Spatial Regional and Level Exceedance estimators. Simulation results and real data examples show the benefits of using the Tukey g-and-h transformation as opposed to standard Gaussian spatial random fields in a real data application for environmental monitoring.

[Exon 19 Deletion and Exon 21 L858R Point Mutation in EGFR Mutation‒Positive Non‒Small Cell Lung Cancer].

Epidermal growth factor receptor(EGFR)is a transmembrane receptor tyrosine kinase the signaling of which is important for growth and progression of cancer. An exon 19 deletion mutation and an exon 21 L858R point mutation are frequently detected as EGFR mutations in patients with non‒small cell lung cancer. This review summarizes the differences in epidemiological, nonclinical, and clinical characteristics between the exon 19 deletion mutation and the exon 21 L858R point mutation.

[Differences between EGFR Exon 19 Deletion and Exon 21 L858R Point Mutation, Frequently Detected EGFR Mutations in Patients with Non-Small Cell Lung Cancer, from a Molecular Biology Viewpoint].

Epidermal growth factor receptor(EGFR)is a transmembrane receptor tyrosine kinase that plays an important role in regulating the growth and progression of cancer via signalling pathways. This review summarizes the differences in EGFR kinase structural changes, stability of active forms, and phosphorylation inhibitory effects of EGFR tyrosine kinase inhibitors between the exon 19 deletion mutation and the exon 21 L858R point mutation, which are frequently detected EGFR mutations in patients with non-small cell lung cancer.

Sensitivity to change and responsiveness of the Balance Evaluation Systems Test (BESTest), Mini-BESTest, and Brief-BESTest in patients with subacute cerebral infarction.

[Purpose] To compare the sensitivity to change and responsiveness of the Balance Evaluation Systems Test, Mini-Balance Evaluation Systems Test, and Brief-Balance Evaluation Systems Test in patients with subacute cerebral infarction. [Participants and Methods] Thirty patients with subacute cerebral infarction participated in this study. The Balance Evaluation Systems Test, Mini-Balance Evaluation Systems Test, Brief-Balance Evaluation Systems Test, Berg Balance Scale, and ambulatory ability were assessed on admission and discharge. Sensitivity to change was calculated using the effect size, standardized response mean, and relative efficiency. Responsiveness was analyzed by comparing the ability of the difference between the scores of the balance assessments at admission and discharge in classifying the participants' ambulatory independence. [Results] All assessments showed significant improvement from admission to discharge. The effect size of the three versions of the Balance Evaluation Systems Test ranged from 0.41 to 0.69. The standardized response mean ranged from 0.75 to 1.28. The cutoff score was 16.7% for the Balance Evaluation Systems Test, 5.5 points for the Mini-Balance Evaluation Systems Test, 1.5 points for the Brief-Balance Evaluation Systems Test, and 3.5 points for the Berg Balance Scale. [Conclusion] The sensitivity to change of the three versions of the Balance Evaluation Systems Test was high or moderate. However, the Mini-Balance Evaluation Systems Test had the highest responsiveness, as determined with the extent of ambulatory independence.

Examination of factors contributing to help-seeking behavior in accessing psychosocial support services among Japanese cancer patients: An application of the segmentation approach.

OBJECTIVE: Various psychosocial support services for cancer patients are available in Japan; however, their utilization rate is low. The present study aimed to examine factors contributing to help-seeking behavior in the use of psychosocial support services among cancer outpatients at three stages: Precontemplation (without adjustment disorder or major depression), Precontemplation (with adjustment disorder or major depression), and Contemplation. METHODS: We conducted a web-based questionnaire survey at two points with a panel of cancer outpatients. We collected data on demographic information, physical status, the use of and intention to use psychosocial support services, psychological distress, attitude toward using psychosocial support services for cancer patients, and social support. RESULTS: In total, 395 cancer patients were analyzed. In the Precontemplation (without adjustment disorder or major depression) stage, resistance to help-seeking (OR = 0.726, P = .011) and future prospects of the Brief Cancer-Related Worry Inventory (OR = 1.012, P = .019) were significant. In the Precontemplation (with adjustment disorder or major depression) stage, only recommendation by medical staff or family (OR = 0.000, P = .026) had a significant effect. In the Contemplation stage, only social and interpersonal problems (OR = 0.942, P = .080) showed a significant (negative) trend. CONCLUSIONS: This study showed that contributing factors differed by stage. To encourage the use of psychosocial support services, it is desirable to recommend the use and to develop interventions for promoting, with responding to patients' conditions and intentions rather than responding to everyone in the same way.

Understanding help-seeking behaviour in relation to psychosocial support services among Japanese cancer patients.

BACKGROUND: There are various psychosocial support services for cancer patients in Japan; however, their utilization rate is lower than in Western countries. The aim of this study was to investigate the actual status of the utilization of such services and the related factors of their use, using the transtheoretical model. METHODS: We conducted an Internet survey of cancer outpatients. They were asked for information on their demographics, physical status and the usage of and intention to use psychosocial support services, and to answer the Hospital Anxiety and Depression Scale. RESULTS: Data of 712 participants were analyzed; 111 had made use of psychosocial support services (15.6%). Participants who were younger, female, had breast cancer, experience with hormone therapy and did not have a good performance status (Karnofsky Performance Scale) more often used such services when comparing users/experiencers with non-users/inexperienced. Of the inexperienced, 538 were in the Precontemplation stage (89.5%), 62 were in the Contemplation stage (10.3%) and one was in the Preparation stage (0.2%). Approximately 35% of those in the Precontemplation stage would correspond to adjustment disorders or major depression. CONCLUSIONS: We showed the degree of cancer patients who have used the psychosocial support services and its contents and revealed the factors related to the utilization of such services in Japan. Our study supports previous reports that cancer patients with high levels of distress do not necessarily seek support, and thus future studies should also examine other modifiable factors considering the medical settings.

Problems, goals and solutions reported by cancer patients participating in group problem-solving therapy.

BACKGROUND: The purpose of the present study was to categorize and develop lists of contents of problems, goals, solution plans generated through the brainstorming work in therapy, and selected solutions for execution, that treated in problem-solving therapy (PST) for cancer patients in clinical settings, and to describe their characteristics. Additionally, examining the associations of problem domains with characteristics of participants, was also aimed. METHODS: We conducted content analysis using records of thirty-one cancer patients (M = 62.6 years old; SD = 10.5) who participated in PST program. RESULTS: Problems were categorized into four domains (e.g. psychological and existential problems; physical problems; social relations; social living environment). Participants under treatment at baseline reported psychological and existential problems most often (P < 0.05). Goals were categorized into four domains (e.g. improving mental health; improving physical functions; improving social relations and improving one's social living environment). Solution plans generated through the brainstorming work in therapy were categorized into four domains (e.g. emotion regulation/cognitive adjustment; health behaviors; adjustment of social relationships and adjusting one's social living environment). Selected solutions for execution were categorized into four domains (e.g. emotion regulation/cognitive adjustment; health behaviors; adjustment of social relationships and adjusting one's social living environment). CONCLUSIONS: We found that various problems, goals and solutions were treated in PST of realistic clinical setting. Creating lists based on our study and making use of it for the materials as aids while implementing the PST or being shared with patients and medical staff would be expected.

Professional identity formation of female doctors in Japan - gap between the married and unmarried.

BACKGROUND: During professional identity formation (PIF), medical students and young doctors enter the process of socialization in medicine with their preexisting personal identities. Here, the authors focused on how gender influences both the professional and personal identities of doctors. The authors' particular research question was how the professional and personal identities of female doctors are formed in Japan, a patriarchal and highly masculinized country, especially before and after marriage and childbirth. METHODS: Narrative inquiry was used as the research methodology. The authors purposively sampled 10 unmarried and 15 married Japanese female physicians with varying lengths of full-time work experience and conducted individual semi-structured face-to-face interviews between July 2013 and February 2015. The authors recorded, transcribed and anonymized the narrative data and extracted themes and representative narratives related to the formation of professional and personal identities. Based on these, the authors developed the master narrative for the whole study. RESULTS: The PIF process by which female physicians integrate personal and professional identities was profoundly affected by gender stereotypes. Further, participant narratives revealed the existence of conflict between married and unmarried female doctors, which created a considerable gap between them. CONCLUSIONS: Female physicians lived with conflicting emotions in a chain of gender stereotype reinforcement. To overcome these issues, we propose that it is necessary to depart from a culture that determines merit based on a fixed sense of values, and instead develop a cultural system and work environment which allows the cultivation of a professional vision that accepts a wide variety of professional and personal identities, and a similarly wide variety of methods by which the two can be integrated.

The use of psychosocial support services among Japanese breast cancer survivors.

BACKGROUND: This study aimed to investigate the use of psychosocial support services, the intention to use these services, and to elucidate the characteristics of survivors most likely to use support services among Japanese breast cancer survivors. METHODS: We invited breast cancer survivors to complete an online questionnaire via an email sent to subscribers of a non-profit organization mailing list. We asked participants questions related to demographics, opinions on the state of psychosocial support services, and their interest in using these services. Participants were also asked to complete the Hospital Anxiety and Depression Scale and the Brief Cancer Worry Inventory (BCWI). RESULTS: We analyzed the data of 171 participants. Those who used some form of psychosocial support service constituted 50.9% of the participant population. Participants used cancer consulting and support center services (13.5%), hospital and non-hospital support groups (12.9%, respectively), psychiatry (11.1%), hospital and non-hospital cancer salons (8.8%, respectively), psychosomatic medicine (8.2%), therapist counseling (6.4%) and psycho-oncology department services (4.1%). Non-users who suffered from adjustment disorders or major depression (52.1%) reported higher total BCWI and the subscale scores had no concrete plans to use psychosocial support services. CONCLUSIONS: The usage levels of psychiatry, psychosomatic medicine and psycho-oncology services in our study were higher than those reported in any previous Japanese study within the psycho-oncology field. Participants joining a breast cancer survivors' mailing list, or their being female, may have led to a higher use of such services. A high degree of distress does not necessarily lead cancer survivors to seek psychosocial support services.

Association between depressive symptoms and changes in sleep condition in the grieving process.

PURPOSE: Bereaved families often suffer from insomnia and depression. However, the associations between depressive state and changes in sleep condition during the grieving process have not been investigated. This study aimed to clarify the prevalence of insomnia symptoms and to explore associations between present depressive state and changes in sleep condition in the grieving process in bereaved families of Japanese patients with cancer. METHODS: A cross-sectional, multicenter survey was conducted in 103 certified palliative care units. A questionnaire asking insomnia symptoms and depressive symptoms by the Center for Epidemiological Studies Depression Scale (CES-D) was mailed to bereaved families (N = 987). The association between present depressive state (CES-D ≥7) and sleep conditions in the grieving process were analyzed. RESULTS: A total of 561 families were enrolled for analysis. Fifty-three percent of family members were considered to be in a depressive state at the time of the investigation. Prevalence of past insomnia was 86.5% at "within a few weeks before the patient's death" (T1) and 84.5% at "within 6 months after the patient's death" (T2) in all bereaved family members. However, in contrast to decreased severity of insomnia between T1 and T2 in the non-depressive group (p < 0.05), severity of insomnia was unchanged in the depressive group during this period (p = 0.139). CONCLUSIONS: Insomnia symptoms are highly prevalent and may be associated with posthumous depressive state in bereaved Japanese families. These results suggest the need for careful observation of changes in sleep condition during the grieving process.

RELAY, Erlotinib Plus Ramucirumab in Untreated, EGFR-Mutated, Metastatic NSCLC: Outcomes by EGFR Exon 19 Deletion Variants.

Introduction: EGFR gene mutations are drivers of NSCLC. The RELAY double-blind, placebo (PBO)-controlled phase 3 study revealed superior progression-free survival (PFS) for ramucirumab plus erlotinib (RAM + ERL) versus PBO (PBO + ERL) in patients with untreated advanced NSCLC and an EGFR-activating mutation. This exploratory analysis evaluated potential associations between EGFR exon 19 deletion (ex19del) variants and clinical outcomes. Methods: Patients (N = 449) were randomized (1:1) to RAM plus ERL or PBO plus ERL. Plasma samples were collected at baseline, on treatment, and at 30-day post-study treatment discontinuation follow-up. Baseline and treatment-emergent gene alterations were investigated by Guardant360 next-generation sequencing. Patients with a valid baseline plasma sample and ex19del were included (RAM + ERL, n = 62; PBO + ERL, n = 72). Results: The most common ex19del variant was E746_A750del (67.2%); EGFR E746 deletions (E746del) occurred more frequently than L747 deletions (74.6% versus 25.4%, respectively). TP53 mutations were the most frequently co-occurring baseline gene alterations. With treatment arms combined, median PFS was 18.0 months versus 12.5 months for patients with uncommon (non-E746_A750del, n = 44) versus common (E746_A750del, n = 90) ex19del variants (hazard ratio [HR] = 1.657 [95% confidence interval or CI:1.044-2.630]). Median PFS was longer with RAM plus ERL versus PBO plus ERL for patients with the common (15.2 versus 9.9 mo; HR = 0.564 [95% CI: 0.344-0.926]) and E746del (15.4 versus 9.9 mo; HR = 0.587 [95% CI: 0.363-0.951]) variants. Treatment-emergent post-progression EGFR T790M rates were higher in the common versus uncommon and E746del versus L747 deletion subgroups. Conclusions: RAM plus ERL provides benefit and improves treatment outcomes for patients with metastatic NSCLC with EGFR ex19del variants.

Pre-post-evaluation of a dementia-specific advance care planning toolkit for Japanese primary care clinicians.

BACKGROUND: The population of people living with dementia (PLwD) continues to grow in Japan where advance care planning (ACP) for PLwD is relatively new. Our aim was to evaluate the feasibility and cultural acceptability of a dementia-specific ACP communication skills toolkit for Japanese primary care clinicians. METHODS: We delivered 13 training sessions in primary care clinics across central Japan and conducted a post-training survey to assess whether the toolkit increased confidence in dementia-specific ACP communication skills and the acceptability of the toolkit with the following four statements: (1) The language in the sessions was clear, (2) The sessions took an appropriate amount of time to complete, (3) The design of the sessions was an effective educational method, and (4) The sessions were culturally appropriate for communication with Japanese patients with dementia and their family members. We asked participants to respond using a 5-point Likert scale from strongly agree to strongly disagree. RESULTS: All participants were Japanese and included 80 physicians (mean age 39.8 years), 33 nurses (mean age 45.7 years), and 58 other participants (mean age 42.9 years), who were 30.0%, 87.9%, and 55.2% female, respectively. Most participants practiced in rural settings. In pre- post-comparisons, participant confidence increased in determining capacity, understanding dementia prognosis, goals of care, eliciting surrogates, recommending self-care practices to families, and leading family meetings (all p < 0.001). Most participants strongly agreed or agreed that the toolkit was an effective method (96.9%), took an appropriate amount of time (94.5%), contained clear language (89.8%), and was culturally appropriate (73.6%). CONCLUSIONS: Dementia-specific ACP communication skills toolkit can be delivered in Japan. Japanese primary care clinicians generally felt the dementia-specific ACP toolkit increased their confidence in ACP communication skills and was acceptable. The language, time, and design were well received, though further work is needed to improve the cultural appropriateness of the toolkit.

Perspectives of medical students on future work-life balance in Japan: A qualitative study using postlecture comments.

Background: Recently, work-life balance (WLB) has grown in popularity among medical professionals, and an increasing number of institutions are including WLB lectures into medical school curricula. In Japan, medical student lectures concerning WLB were given in at least 50% of universities. However, with these changes in social awareness, it is not fully clear how current medical students view WLB. The purpose of this study is to explore how Japanese medical students think about their future WLB from the perspective of constructivism. Method: We used one of the present authors' work career and life cycle as an example of a physician's career in a lecture for medical students on community medicine in 2020. Students were asked to remark on their thoughts on the talk and their views on future WLB, and we analyzed their comments qualitatively to understand the current male and female medical students' perspectives on future WLB. Result: We used the feedback of 119 participants (71 males and 48 females). Most students, regardless of gender, thought WLB was essential, but the factors they mentioned as being connected to WLB mirrored the continuing traditional notions of gender-based division of labor and doctors' fixed-job image. Male students' views, on the other hand, were more varied, reflecting recent generational shifts. Conclusions: For the improved WLB in medical doctors, it would be required to tackle the problem from several angles, including not just increasing support for WLB but also fostering an awareness of the essence of WLB in pregraduate medical school.

Relationship between posttraumatic growth and help-seeking behavior in use of psychosocial support services among patients with cancer.

PURPOSE: Cancer survivors who used psychosocial support services often report posttraumatic growth (PTG). This refers to positive psychological changes that may occur as the five domains as a result of the challenges they face. Opposing relationship also might exist. This study aimed to examine the relationship between PTG and help-seeking behavior (HSB). METHODS: In total, 710 participants completed an online survey at Time1. Of those, 395 who reported not using any psychosocial support services at Time1 were asked to participate in the Time2 survey and completed a questionnaire. The participants provided demographic information, the experiences of using psychosocial support services, and the overall and five domains of PTG. RESULTS: Those who experienced HSB at Time1 reported a higher PTG, and two of the PTG domains, Appreciation of Life and New Possibilities, than those who did not used services. Mixed ANOVAs showed the main effects of the HSB on the overall PTG, Appreciation of Life, and New Possibilities. Hierarchical logistic regression analyses showed that Appreciation of Life at Time1 was significantly related to the engaging in HSB at Time2. CONCLUSION: Those who received psychosocial support services reported a higher PTG. Participants may have also engaged in HSB because they had experienced PTG. People who are likely to seek help and experience PTG may share common characteristics. IMPLICATIONS FOR CANCER SURVIVORS: Support for those who do not fit the existing PTG and the use of psychosocial support services should also be considered.

COVID-19 case prediction using emotion trends via Twitter emoji analysis: A case study in Japan.

Introduction: The worldwide COVID-19 pandemic, which began in December 2019 and has lasted for almost 3 years now, has undergone many changes and has changed public perceptions and attitudes. Various systems for predicting the progression of the pandemic have been developed to help assess the risk of COVID-19 spreading. In a case study in Japan, we attempt to determine whether the trend of emotions toward COVID-19 expressed on social media, specifically Twitter, can be used to enhance COVID-19 case prediction system performance. Methods: We use emoji as a proxy to shallowly capture the trend in emotion expression on Twitter. Two aspects of emoji are studied: the surface trend in emoji usage by using the tweet count and the structural interaction of emoji by using an anomalous score. Results: Our experimental results show that utilizing emoji improved system performance in the majority of evaluations.

Impact of ramucirumab plus erlotinib on circulating cell-free DNA from patients with untreated metastatic non-small cell lung cancer with EGFR-activating mutations (RELAY phase 3 randomized study).

Background: An exploratory, proof-of-concept, liquid biopsy addendum to examine biomarkers within cell-free DNA (cfDNA) in the RELAY phase 3, randomized, double-blind, placebo-controlled study was conducted. RELAY showed improved progression-free survival (PFS) with ramucirumab (RAM), a human immunoglobulin G1 vascular endothelial growth factor receptor 2 antagonist, plus erlotinib (ERL), a tyrosine kinase inhibitor, compared with placebo (PL) plus ERL. Methods: Treatment-naïve patients with endothelial growth factor receptor (EGFR)-mutated metastatic non-small cell lung cancer were randomized (1:1) to RAM + ERL or PL + ERL. Plasma samples were collected at baseline, on treatment, and at 30-day post-study treatment discontinuation follow-up. Baseline and treatment-emergent gene alterations and EGFR-activating mutation allele counts were investigated by next-generation sequencing (NGS) and droplet digital polymerase chain reaction (ddPCR), respectively. cfDNA concentration and fragment size were evaluated by real-time polymerase chain reaction and the BioAnalyzer. Patients with a valid baseline plasma sample were included (70 RAM + ERL, 61 PL + ERL). Results: TP53 mutation was the most frequently co-occurring baseline gene alteration (43%). Post-study treatment discontinuation EGFR T790M mutation rates were 54.5% (6/11) and 41.2% (7/17) by ddPCR, and 22.2% (2/9) and 29.4% (5/17) by NGS, in the RAM + ERL and PL + ERL arms, respectively. EGFR-activating mutation allele count decreased at Cycle 4 in both treatment arms and was sustained at follow-up with RAM + ERL. PFS improved for patients with no detectable EGFR-activating mutation at Cycle 4 vs. those with detectable EGFR-activating mutation. Total cfDNA concentration increased from baseline at Cycle 4 and through to follow-up with RAM + ERL. cfDNA fragment size was similar between treatment arms at baseline [mean (standard deviation) base pairs: RAM + ERL, 173.4 (2.6); PL + ERL, 172.9 (3.2)] and was shorter at Cycle 4 with RAM + ERL vs. PL + ERL [169.5 (2.8) vs. 174.1 (3.3), respectively; P<0.0001]. Baseline vs. Cycle 4 paired analysis showed a decrease in cfDNA fragment size for 84% (48/57) and 23% (11/47) of patient samples in the RAM + ERL and PL + ERL arms, respectively. Conclusions: EGFR-activating mutation allele count was suppressed, total cfDNA concentration increased, and short fragment-sized cfDNA increased with RAM + ERL, suggesting the additional anti-tumor effect of RAM may contribute to the PFS benefit observed in RELAY with RAM + ERL vs. PL + ERL. Trial Registration: ClinicalTrials.gov; identifier: NCT02411448.