Rapid discovery of monoclonal antibodies by microfluidics-enabled FACS of single pathogen-specific antibody-secreting cells.

Monoclonal antibodies are increasingly used to prevent and treat viral infections and are pivotal in pandemic response efforts. Antibody-secreting cells (ASCs; plasma cells and plasmablasts) are an excellent source of high-affinity antibodies with therapeutic potential. Current methods to study antigen-specific ASCs either have low throughput, require expensive and labor-intensive screening or are technically demanding and therefore not widely accessible. Here we present a straightforward technology for the rapid discovery of monoclonal antibodies from ASCs. Our approach combines microfluidic encapsulation of single cells into an antibody capture hydrogel with antigen bait sorting by conventional flow cytometry. With our technology, we screened millions of mouse and human ASCs and obtained monoclonal antibodies against severe acute respiratory syndrome coronavirus 2 with high affinity (<1 pM) and neutralizing capacity (<100 ng ml-1) in 2 weeks with a high hit rate (>85% of characterized antibodies bound the target). By facilitating access to the underexplored ASC compartment, the approach enables efficient antibody discovery and immunological studies into the generation of protective antibodies.

Intratumoral antigen signaling traps CD8+ T cells to confine exhaustion to the tumor site.

Immunotherapy advances have been hindered by difficulties in tracking the behaviors of lymphocytes after antigen signaling. Here, we assessed the behavior of T cells active within tumors through the development of the antigen receptor signaling reporter (AgRSR) mouse, fate-mapping lymphocytes responding to antigens at specific times and locations. Contrary to reports describing the ready egress of T cells out of the tumor, we find that intratumoral antigen signaling traps CD8+ T cells in the tumor. These clonal populations expand and become increasingly exhausted over time. By contrast, antigen-signaled regulatory T cell (Treg) clonal populations readily recirculate out of the tumor. Consequently, intratumoral antigen signaling acts as a gatekeeper to compartmentalize CD8+ T cell responses, even within the same clonotype, thus enabling exhausted T cells to remain confined to a specific tumor tissue site.

Comprehensive identification of pathogenic microbes and antimicrobial resistance genes in food products using nanopore sequencing-based metagenomics.

Foodborne pathogens, particularly antimicrobial-resistant (AMR) bacteria, remain a significant threat to global health. Given the limitations of conventional culture-based approaches, which are limited in scope and time-consuming, metagenomic sequencing of food products emerges as a promising solution. This method provides a fast and comprehensive way to detect the presence of pathogenic microbes and antimicrobial resistance genes (ARGs). Notably, nanopore long-read sequencing provides more accurate bacterial taxonomic classification in comparison to short-read sequencing. Here, we revealed the impact of food types and attributes (origin, retail place, and food processing methods) on microbial communities and the AMR profile using nanopore metagenomic sequencing. We analyzed a total of 260 food products, including raw meat, sashimi, and ready-to-eat (RTE) vegetables. Clostridium botulinum, Acinetobacter baumannii, and Vibrio parahaemolyticus were identified as the top three foodborne pathogens in raw meat and sashimi. Importantly, even with low pathogen abundance, higher percentages of samples containing carbapenem and cephalosporin resistance genes were identified in chicken and RTE vegetables, respectively. In parallel, our results demonstrated that fresh, peeled, and minced foods exhibited higher levels of pathogenic bacteria. In conclusion, this comprehensive study offers invaluable data that can contribute to food safety assessments and serve as a basis for quality indicators.

Prevalence and assessment tools of cancer-related cognitive impairment in lung cancer survivors: a systematic review and proportional meta-analysis.

PURPOSE: Cancer-related cognitive impairment (CRCI) is a significant risk factor influencing the quality of life in lung cancer survivors. No absolute assessment tool has been confirmed to assess CRCI in lung cancer survivors. This review was undertaken to pool the overall prevalence of CRCI and to summarize the assessment tools in assessing CRCI among lung cancer survivors. METHODS: PubMed, Cochrane Library, Embase, CINAHL, and CNKI were searched to retrieve articles reported CRCI prevalence. Summary prevalence estimates were pooled using a random effects model, along with corresponding 95% prediction intervals (PIs). The Freeman-Tukey double arcsine transformation of proportions was incorporated in the analysis. Additionally, subgroup analysis, meta-regression, and leave-one-out analysis were performed. RESULTS: A total of 12 studies, involving 1934 survivors, were included in the review. All of these studies were found to have a low risk of bias in terms of their methodological quality. Four studies (33.3%) utilized the International Cognition and Cancer Task Force (ICCTF) criteria to identify CRCI through neuropsychological tests. The pooled prevalence rate of CRCI was found to be 26% (95% PI, 16-37%), I2 = 95.97%. The region in which the studies were conducted was identified as a significant factor contributing to this heterogeneity (p = 0.013). No indication of small-study effects was found (Egger's test: p = 0.9191). CONCLUSION: This review provides an overview of CRCI prevalence and assessment tools in lung cancer survivors. The findings can serve as epidemiological evidence to enhance clinicians' and researchers' understanding of early detection and assessment.

Teaching spirituality to Canadian medical students: students' perceptions of a spiritual history taking clinical skills session.

Spirituality involves one's sense of purpose, connection with others, and ability to find meaning in life. We implemented a three-year pilot of a spiritual history taking (SHT) clinical skills session. In small groups, medical students discussed and practiced SHT with clinical scenarios and the FICA framework and received preceptor and peer feedback. Post-session focus groups and interviews demonstrated student perceptions of improved comfort, knowledge, and awareness of discussing spirituality with patients. This innovation may support improved clinical skills teaching across other health professions institutions to better prepare students to recognize patients' spiritual needs and provide more holistic, culturally competent care.

La spiritualité touche au sentiment d'avoir une raison d'être, à la relation à l'autre et à la capacité de trouver un sens à la vie1. Nous avons mis en place, comme projet pilote de trois ans, une séance visant l'acquisition de compétences cliniques portant sur l'anamnèse spirituelle (AS). En petits groupes, les étudiants discutaient de l'anamnèse spirituelle et la mettaient en pratique au moyen de scénarios cliniques et du questionnaire d'anamnèse spirituelle FICA2, puis recevaient des commentaires de la part de leur précepteur et de leurs pairs. Les groupes de discussion et les entretiens après les séances ont montré que les étudiants se sentaient mieux informés, plus à l'aise et plus conscients de la nécessité de parler de spiritualité avec les patients. Cette innovation peut contribuer à améliorer l'enseignement des compétences cliniques dans d'autres professions de la santé pour mieux préparer les étudiants à reconnaître les besoins spirituels des patients et à fournir des soins plus holistiques et culturellement adaptés.

Natural statistics support a rational account of confidence biases.

Previous work has sought to understand decision confidence as a prediction of the probability that a decision will be correct, leading to debate over whether these predictions are optimal, and whether they rely on the same decision variable as decisions themselves. This work has generally relied on idealized, low-dimensional models, necessitating strong assumptions about the representations over which confidence is computed. To address this, we used deep neural networks to develop a model of decision confidence that operates directly over high-dimensional, naturalistic stimuli. The model accounts for a number of puzzling dissociations between decisions and confidence, reveals a rational explanation of these dissociations in terms of optimization for the statistics of sensory inputs, and makes the surprising prediction that, despite these dissociations, decisions and confidence depend on a common decision variable.

A systematic review to summarize treatment patterns, guidelines, and characteristics of patients with renal cell carcinoma in the Asia-Pacific region.

INTRODUCTION: This systematic review evaluated treatment patterns and guidelines in advanced/metastatic and adjuvant renal cell carcinoma (RCC) in the Asia-Pacific region. AREAS COVERED: Embase, PubMed, and congresses were searched for observational studies and guidelines in accordance with PRISMA. Records published during 2016-2021 (2019-2021 for congresses) were included. EXPERT OPINION: Nine studies and three guidelines were identified overall. In advanced/metastatic RCC, the most common treatments were tyrosine kinase inhibitors (TKIs) (notably sunitinib: 33-100%) for first-line, and everolimus (13-85%) or axitinib (2-89%) for second-line therapy. In adjuvant RCC, sunitinib was most used (54%), followed by mammalian target of rapamycin inhibitors (mTORis, 27%) with immunotherapy being less common (16%). The guidelines provided varying recommendations for advanced/metastatic RCC. For first-line in advanced/metastatic clear cell RCC (the most common subtype), guidelines recommended mTORis (everolimus for poor-risk patients) (India, 2016); clinical study enrollment for high-risk patients or TKIs for low- to medium-risk patients (China, 2019); or immunotherapy based on survival benefits over sunitinib; dose adjustment was also recommended to manage TKI toxicities (Hong Kong, 2019). The landscape remained more static in the adjuvant setting, but best practice was uncertain. No clear trends were identified in patient characteristics.

Acupuncture for chemotherapy-associated insomnia in breast cancer patients: an assessor-participant blinded, randomized, sham-controlled trial.

BACKGROUND: Insomnia is a highly prevalent symptom occurred during and post-chemotherapy. Acupuncture may have beneficial effects in the management of chemotherapy-associated insomnia. This study was conducted to determine the efficacy and safety of acupuncture in improving chemotherapy-associated insomnia in breast cancer patients. METHODS: This assessor-participant blinded, randomized, sham-controlled trial was conducted from November 2019 to January 2022 (follow-up completed July 2022). Participants were referred by oncologists from two Hong Kong hospitals. Assessments and interventions were conducted at the outpatient clinic of School of Chinese Medicine, the University of Hong Kong. The 138 breast cancer patients with chemotherapy-associated insomnia were randomly assigned to receive either 15 sessions of active acupuncture regimen by combining needling into body acupoints and acupressure on auricular acupoints or sham acupuncture control (69 each) for 18 weeks, followed by 24 weeks of follow-up. The primary outcome was measured using Insomnia Severity Index (ISI). Secondary outcomes included the Pittsburgh Sleep Quality Index, Actiwatch and sleep diary for sleep parameters, depression and anxiety, fatigue and pain, and quality of life. RESULTS: There were 87.7% (121/138) participants who completed the primary endpoint (week-6). The active acupuncture regimen was not superior to the sham control in reducing ISI score from baseline to 6 weeks (mean difference: - 0.4, 95% CI - 1.8-1.1; P = 0.609), but produced short-term treatment and long-term follow-up better outcomes in improving sleep onset latency, total sleep time, sleep efficiency, anxiety, depression, and quality of life. Participants of the active acupuncture group had a pronouncedly higher cessation rate of sleeping medications than the sham control (56.5% vs. 14.3%, P = 0.011). All treatment-related adverse events were mild. No participants discontinued treatments due to adverse events. CONCLUSION: The active acupuncture regimen could be considered as an effective option for the management of chemotherapy-associated insomnia. It also could serve as a tapering approach to reduce and even replace the use of sleeping medications in breast cancer patients. Trial registration Clinicaltrials.gov : NCT04144309. Registered 30 October 2019.

Home and hub: pet trade and traditional medicine impact reptile populations in source locations and destinations.

The pet trade and Traditional Chinese Medicine (TCM) consumption are major drivers of global biodiversity loss. Tokay geckos (Gekko gecko) are among the most traded reptile species worldwide. In Hong Kong, pet and TCM markets sell tokay geckos while wild populations also persist. To clarify connections between trade sources and destinations, we compared genetics and stable isotopes of wild tokays in local and non-local populations to dried individuals from TCM markets across Hong Kong. We found that TCM tokays are likely not of local origin. Most wild tokays were related to individuals in South China, indicating a probable natural origin. However, two populations contained individuals more similar to distant populations, indicating pet trade origins. Our results highlight the complexity of wildlife trade impacts within trade hubs. Such trade dynamics complicate local legal regulation when endangered species are protected, but the same species might also be non-native and possibly damaging to the environment.

Parental Feeding Practices in Families Experiencing Food Insecurity: A Scoping Review.

Parental feeding practices and styles influence child diet quality and growth. The extent to which these factors have been assessed in the context of disadvantage, particularly household food insecurity (HFI), is unknown. This is important, as interventions designed to increase responsive practices and styles may not consider the unique needs of families with HFI. To address this gap, a scoping review of studies published from 1990 to July 2021 in three electronic databases was conducted. A priori inclusion criteria were, population: families with children aged 0-5 years experiencing food insecurity and/or disadvantage; concept: parental feeding practices/behaviours/style; and context: high income countries. The search identified 12,950 unique papers, 504 full-text articles were screened and 131 met the inclusion criteria. Almost all the studies (91%) were conducted in the United States with recruitment via existing programs for families on low incomes. Only 27 papers assessed feeding practices or styles in the context of HFI. Of the eleven interventions identified, two assessed the proportion of participants who were food insecure. More research is required in families outside of the United States, with an emphasis on comprehensive and valid measures of HFI and feeding practices. Intervention design should be sensitive to factors associated with poverty, including food insecurity.

Refining TNM-8 M1 categories with anatomic subgroups for previously untreated de novo metastatic nasopharyngeal carcinoma.

PURPOSE: To propose a refined M1 classification in de novo metastatic nasopharyngeal carcinoma (NPC) based on pooled data from two academic institutions. METHODS: Previously untreated de novo M1 NPC patients prospectively treated at The University of Hong Kong (N = 69) and Fujian Cancer Hospital (N = 114) between 2007 and 2016 were recruited and randomized in a 2:1 ratio to generate training (N = 120) and validation (N = 63) cohorts, respectively. Multivariable analysis (MVA) was performed for the training and validation cohorts to identify anatomic prognostic factors for overall survival (OS). Recursive partitioning analysis (RPA) was performed which incorporated the anatomic prognostic factors identified in the MVA to derive Anatomic-RPA groups which stratified OS in the training cohort, and were then validated in the validation cohort. RESULTS: Median follow-up for the training and validation cohorts was 27.2 and 30.2 months with 3-year OS of 51.6% and 51.1%, respectively. MVA revealed that co-existing liver-bone metastases was the only factor prognostic for OS in both the training and validation cohorts. Anatomic-RPA separated M1 disease into M1a (no co-existing liver-bone metastases) and M1b (co-existing liver-bone metastases) with median OS 39.5 and 23.7 months, respectively (p = 0.004) in the training cohort. RPA for the validation cohort also confirmed good segregation with co-existing liver-bone metastases with median OS 47.7 and 16.0 months, respectively (p = 0.008). CONCLUSION: Our proposal to subdivide de novo M1 NPC into M1a (no co-existing liver-bone metastases) vs. M1b (co-existing liver-bone metastases) provides better OS segregation.

Unbiased cell surface proteomics identifies SEMA4A as an effective immunotherapy target for myeloma.

The accessibility of cell surface proteins makes them tractable for targeting by cancer immunotherapy, but identifying suitable targets remains challenging. Here we describe plasma membrane profiling of primary human myeloma cells to identify an unprecedented number of cell surface proteins of a primary cancer. We used a novel approach to prioritize immunotherapy targets and identified a cell surface protein not previously implicated in myeloma, semaphorin-4A (SEMA4A). Using knock-down by short-hairpin RNA and CRISPR/nuclease-dead Cas9 (dCas9), we show that expression of SEMA4A is essential for normal myeloma cell growth in vitro, indicating that myeloma cells cannot downregulate the protein to avoid detection. We further show that SEMA4A would not be identified as a myeloma therapeutic target by standard CRISPR/Cas9 knockout screens because of exon skipping. Finally, we potently and selectively targeted SEMA4A with a novel antibody-drug conjugate in vitro and in vivo.

Statins mediate anti- and pro-tumourigenic functions by remodelling the tumour microenvironment.

Anti-cancer properties of statins are controversial and possibly context dependent. Recent pathology/epidemiology studies of human lung adenocarcinoma showed reduced pro-tumourigenic macrophages associated with a shift to lower-grade tumours amongst statin users but, paradoxically, worse survival compared with that of non-users. To investigate the mechanisms involved, we have characterised mouse lung adenoma/adenocarcinoma models treated with atorvastatin. Here, we show that atorvastatin suppresses premalignant disease by inhibiting the recruitment of pro-tumourigenic macrophages to the tumour microenvironment, manifested in part by suppression of Rac-mediated CCR1 ligand secretion. However, prolonged atorvastatin treatment leads to drug resistance and progression of lung adenomas into invasive disease. Pathological progression is not driven by acquisition of additional driver mutations or immunoediting/evasion but is associated with stromal changes including the development of desmoplastic stroma containing Gr1+ myeloid cells and tertiary lymphoid structures. These findings show that any chemopreventive functions of atorvastatin in lung adenocarcinoma are overridden by stromal remodelling in the long term, thus providing mechanistic insight into the poor survival of lung adenocarcinoma patients with statin use.

Electroacupuncture Plus Auricular Acupressure on Chemotherapy-Related Insomnia in Patients With Breast Cancer (EACRI): Study Protocol for a Randomized, Sham-Controlled Trial.

OBJECTIVE: Insomnia is a highly prevalent and disturbing symptom in breast cancer patients under or post chemotherapy. If not appropriately treated, it can persist for years after the completion of cancer treatments. Acupuncture has been widely used for alleviating insomnia. The aim of this study is to examine the feasibility, efficacy and safety of acupuncture for chemotherapy-related insomnia among patients with breast cancer. MATERIALS AND METHODS: This is a trial protocol for a randomized, sham-controlled, subject- and assessor-blinded clinical trial. A total of 138 eligible participants will be assigned randomly to acupuncture or sham control group at a ratio of 1:1. Participants in acupuncture group will receive electroacupuncture (EA) plus auricular acupressure (AA) treatment, while subjects in sham acupuncture group will receive sham EA plus sham AA. Both acupuncture and sham treatments will be given twice weekly for 6 weeks, followed by maintenance treatments once every 4 weeks for 12 weeks (15 sessions totally). The primary outcome is the change of Insomnia Severity Index score between baseline and the end of 6-week treatment. Secondary outcome measurements include Actiwatch, sleep diary, Pittsburgh Sleep Quality Index, Functional Assessment of Cancer Therapy-Breast Cancer, Hospital Anxiety and Depression Scale, Brief Pain Inventory-Short Form, Brief Fatigue Inventory, Acupuncture Expectancy Scale, credibility, and adverse events. Participants will be followed up to 42 weeks. CONCLUSIONS: This trial will expand our understanding of the feasibility, efficacy, and safety of acupuncture as a treatment for alleviating chemotherapy-related insomnia in patients with breast cancer. EA plus AA, if proven to be effective, can be implemented into routine settings to play a role in insomnia management for patients with breast cancer.

Systematic Review with Meta-Analysis: Effectiveness and Safety of Acupuncture as Adjuvant Therapy for Side Effects Management in Drug Therapy-Receiving Breast Cancer Patients.

OBJECTIVE: To investigate the potential benefits and safety of acupuncture on managing side effects induced by drug therapies in patients with breast cancer using a PRISMA standard systematic review and meta-analysis. METHODS: Published randomised controlled trials from nine databases in English and Chinese language were searched. Trials with a real acupuncture treatment group and a control group with sham acupuncture, no treatment, or waitlist control were included. The primary outcome of this study was the therapeutic effects on five symptoms induced by drug therapies, including gastrointestinal disorder, neuropathy, arthralgia, joint symptoms, and cognitive impairment. The quality of life was assessed as a secondary outcome. The risk of bias of each study was analysed according to the Cochrane Handbook. RESULTS: Sixteen randomised controlled trials with 1189 participants were included in the meta-analysis. The primary outcome and all subgroup analyses showed statistically significant improvements in the management of side effects by real acupuncture. The quality of life of patients has enhanced during the treatment. CONCLUSION: Although the number of publications is limited, a clear preliminary conclusion could be drawn by the meta-analysis, suggesting the beneficial adjuvant role of acupuncture in patients with breast cancer who receive drug therapies. No serious adverse events were observed from all the RCTs, and the safety of acupuncture is ascertained. More standardised and sophisticated large-scale randomised controlled trials are needed to evaluate the findings further.

Efficacy and Safety of Chinese Herbal Medicine on Treatment of Breast Cancer: A Meta-analysis of Randomized Controlled Trials.

Breast cancer is currently the most common cancer in women, and it accounts for 11.6% of all cancer diagnoses in 2018. Breast cancer patients frequently resort to alternative medicine in addition to conventional Western therapy. This study is to evaluate clinical effectiveness of Chinese herbal medicine (CHM) on breast cancer by conducting meta-analyses on 81 randomized controlled trials (RCTs) with a total of 7215 subjects from eight databases. All RCTs compared patients using Western therapy alone and those using additional CHM therapy to evaluate the difference of primary (tumor response, mean time to progression (mTTP), overall survival (OS) and progression free survival (PFS)) and secondary outcome measures (tumor markers). Results showed that under the RECIST1.1 criteria, 52% patients with additional CHM therapy (67%, under WHO criteria) achieved either a complete response (CR) or a partial response (PR), compared to 38% patients with Western therapy alone (53%, under the WHO criteria). The risk ratio was 1.31 ([Formula: see text] < 0.00001, 95% CI = 1.15-1.50) for patients with CHM plus Western therapy and 1.25 ([Formula: see text] < 0.00001, 95% CI = 1.18-1.98) for those with Western therapy. Moreover, patients with complementary CHM therapy were associated with an mTTP of 2.79 months longer ([Formula: see text] < 0.00001) and an OS of 1.90 months longer ([Formula: see text] < 0.00001); they also had an increase in 3-year PFS ([Formula: see text]= 0.002), 2- ([Formula: see text]= 0.0002) and 5-year ([Formula: see text]= 0.006) OS rates. Therefore, complementary CHM therapy might demonstrate clinical benefits for breast cancer patients in terms of tumor response and survival. Clinical studies with further stratification of tumor stages and intervention types are highly warranted.

Electroacupuncture Plus Auricular Acupressure for Chemotherapy-Associated Insomnia in Breast Cancer Patients: A Pilot Randomized Controlled Trial.

OBJECTIVE: Chemotherapy-associated insomnia is a highly prevalent complaint in breast cancer patients. This study was undertaken to evaluate the safety, feasibility, and preliminary effectiveness of electroacupuncture plus auricular acupressure for chemotherapy-associated insomnia in patients with breast cancer. MATERIALS AND METHODS: In this randomized, wait-list controlled trial, thirty breast cancer patients under or post chemotherapy with insomnia were randomly allocated to the acupuncture or wait-list control group. Participants in acupuncture group received electroacupuncture plus auricular acupressure treatment twice weekly for 6 weeks. Participants in wait-list group received the same regimen of treatment after 6-week of waiting period. Insomnia Severity Index (ISI) served as the primary outcome measurement. Secondary outcomes were sleep parameters recorded with sleep diary and actiwatch, as well as the scores of Pittsburgh Sleep Quality Index (PSQI), Hospital Anxiety and Depression Scale (HADS), and Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B). RESULTS: Twenty-eight participants completed study (13 in the acupuncture group vs 15 in the wait-list control group). At week-6 post-intervention, ISI score change from baseline showed significant between-group difference favoring acupuncture group of -2.9 points (95% CI: -5.2 to -0.6, P = .014). The acupuncture group showed greater improvements in the total sleep time recorded by sleep diary (P = .026), scores of PSQI (P = .012), HADS-depression (P = .020), and FACT-B (P < .001) compared with the control group. Improvements were maintained at week-10 and week-14 follow-ups. CONCLUSIONS: Acupuncture is safe, feasible, and effective for chemotherapy-associated insomnia in breast cancer patients under or post chemotherapy. A larger sample size randomized clinical trial is warranted to confirm the present findings. CLINICAL TRIAL REGISTRATION: NCT03762694.

The Adjunctive Effect of Acupuncture for Advanced Cancer Patients in a Collaborative Model of Palliative Care: Study Protocol for a 3-Arm Randomized Trial.

BACKGROUND: Cancer is the second leading cause of death before the age of 70. Improved cancer survival has put increasing demands on cancer care. Palliative care is the specialized multi-disciplinary care providing relief from the pain, symptoms, and stress of serious illness. The study aims to evaluate the adjunctive effect of acupuncture for advanced cancer patients in a collaborative model of palliative care. METHODS/DESIGN: This is a single-blinded, randomized, sham-controlled trial. One hundred twenty advanced cancer patients undergoing palliative care will be randomized in a ratio of 2:1:1 to manual acupuncture plus standard care group (ASC), sham acupuncture plus standard care group (SSC), and standard care group (SC). Patients in ASC and SSC will receive 9 sessions of acupuncture or sham acupuncture for 3 weeks, and will be followed up for 2 months. The primary measure is the change from baseline score of the Edmonton Symptom Assessment System at 3 weeks. The secondary measures include the Brief Fatigue Inventory, Hospital Anxiety and Depression Scale, Insomnia Severity Index, Numeric Rating Scale, and European Organization for Research and Treatment of Cancer Quality of Life 15 items Questionnaire for Palliative Care. DISCUSSION: The finding of this trial will provide high-quality evidence on the adjunctive effect of acupuncture to standard care on advanced cancer patients undergoing palliative care. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04398875 (https://www.clinicaltrials.gov/ct2/show/NCT04398875), Registered on 21 May 2020.

A Cost-Effectiveness Analysis of Systemic Therapy for Metastatic Hormone-Sensitive Prostate Cancer.

BACKGROUND: Currently, approved first-line treatment options of metastatic hormone-sensitive prostate cancer (mHSPC) include (1) androgen deprivation therapy (ADT) alone, ADT plus one of the following: (2) docetaxel, (3) abiraterone, (4) enzalutamide, and (5) apalutamide. The high cost of novel androgen receptor pathway inhibitors warrants an understanding of the combinations' value by considering both efficacy and cost. OBJECTIVE: This study aimed to compare the cost-effectiveness of these five treatment options in mHSPC from the US payer perspective to guide treatment sequence. METHODS: A Markov model was developed to compare the lifetime cost and effectiveness of these five first-line treatment options for mHSPC using outcomes data from published literature. Health outcomes were measured in life-years and quality-adjusted life-years (QALYs). Drug costs were obtained from the Veterans Affairs Pharmaceutical Catalog. We extrapolated survival beyond closure of the trials. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Life-years, QALYs, lifetime costs, and incremental cost-effectiveness ratios (ICERs) were estimated. Univariable, 2-way, and probabilistic sensitivity analyses were performed to evaluate parameter uncertainty. A willingness-to-pay (WTP) threshold of US$100,000 per QALY was used. RESULTS: Compared to ADT alone, docetaxel plus ADT provided a 0.28 QALY gain at an ICER of US$12,870 per QALY. Abiraterone plus ADT provided an additional 1.70 QALYs against docetaxel plus ADT, with an ICER of US$38,897 per QALY. Compared to abiraterone plus ADT, enzalutamide plus ADT provided an additional 0.87 QALYs at an ICER of US$509,813 per QALY. Apalutamide plus ADT was strongly dominated by enzalutamide plus ADT. Given the WTP threshold of US$100,000 per QALY, abiraterone plus ADT represented high-value health care. CONCLUSIONS: Abiraterone plus ADT is the preferred treatment option for men with mHSPC at a WTP threshold of US$100,000 per QALY.

Between-subject correlation of heart rate variability predicts movie preferences.

We introduce a novel and simple method for assessing audiences' emotional responses to audiovisuals (e.g. films). Viewers (N = 21) watched movies and TV commercials from different genres while wearing photoplethysmography (PPG) optic sensors on their wrists. Heart rate variability (HRV) synchrony was observed among the audience. Based on this between-subject synchrony measure, we identified emotionally arousing segments from the materials. New participants (N = 24; N = 16) were then invited to watch these identified segments along with some randomly selected segments as control; they reported that the former was more engaging (effect size w = .67; w = .5). This finding was confirmed in an online study with a larger cohort (N = 300). While some specific effects varied depending on movie genre or gender, HRV-based editing generally performed better than the control. These findings suggest that HRV synchrony can be used as a new tool for audience psychology, and potentially also for automatically creating short trailers out of movies in a principled manner while taking into account the human perspective.