Hyperspectral dark-field microscopy of human breast lumpectomy samples for tumor margin detection in breast-conserving surgery.

Significance: Hyperspectral dark-field microscopy (HSDFM) and data cube analysis algorithms demonstrate successful detection and classification of various tissue types, including carcinoma regions in human post-lumpectomy breast tissues excised during breast-conserving surgeries. Aim: We expand the application of HSDFM to the classification of tissue types and tumor subtypes in pre-histopathology human breast lumpectomy samples. Approach: Breast tissues excised during breast-conserving surgeries were imaged by the HSDFM and analyzed. The performance of the HSDFM is evaluated by comparing the backscattering intensity spectra of polystyrene microbead solutions with the Monte Carlo simulation of the experimental data. For classification algorithms, two analysis approaches, a supervised technique based on the spectral angle mapper (SAM) algorithm and an unsupervised technique based on the K-means algorithm are applied to classify various tissue types including carcinoma subtypes. In the supervised technique, the SAM algorithm with manually extracted endmembers guided by H&E annotations is used as reference spectra, allowing for segmentation maps with classified tissue types including carcinoma subtypes. Results: The manually extracted endmembers of known tissue types and their corresponding threshold spectral correlation angles for classification make a good reference library that validates endmembers computed by the unsupervised K-means algorithm. The unsupervised K-means algorithm, with no a priori information, produces abundance maps with dominant endmembers of various tissue types, including carcinoma subtypes of invasive ductal carcinoma and invasive mucinous carcinoma. The two carcinomas' unique endmembers produced by the two methods agree with each other within <2% residual error margin. Conclusions: Our report demonstrates a robust procedure for the validation of an unsupervised algorithm with the essential set of parameters based on the ground truth, histopathological information. We have demonstrated that a trained library of the histopathology-guided endmembers and associated threshold spectral correlation angles computed against well-defined reference data cubes serve such parameters. Two classification algorithms, supervised and unsupervised algorithms, are employed to identify regions with carcinoma subtypes of invasive ductal carcinoma and invasive mucinous carcinoma present in the tissues. The two carcinomas' unique endmembers used by the two methods agree to <2% residual error margin. This library of high quality and collected under an environment with no ambient background may be instrumental to develop or validate more advanced unsupervised data cube analysis algorithms, such as effective neural networks for efficient subtype classification.

Assessment of Nutritional Risk Scores (the Nutritional Risk Screening 2002 and Modified Nutrition Risk in Critically Ill Scores) as Predictors of Mortality in Critically Ill Patients on Extracorporeal Membrane Oxygenation.

Nutritional risk is associated with intensive care unit (ICU) stay and mortality, the Nutritional Risk Screening 2002 (NRS 2002) and the modified Nutritional Risk in the Critically Ill (mNUTRIC) score are assessment instruments and useful in predicting the risk regarding mortality in ICU patients. Our aim was to assess the effects of mNUTRIC and NRS 2002 on mortality in patients on extracorporeal membrane oxygenation (ECMO). A retrospective cohort study was performed and 78 patients were included for final analysis. In the current study, the NRS 2002 and the mNUTRIC score within 24 hours before starting ECMO were applied to assess patients' nutritional status on ECMO and explore the relationship between nutritional status and patient outcomes. This study suggests that both mNUTRIC and NRS 2002 scores were found to be significant independent risk and prognostic factors for in-hospital and 90 day morality among ECMO patients based on multivariable logistic regression analysis (p < 0.05), with those in the high-risk group having higher in-hospital and 90 day mortality rates than those identified as being at low risk (p < 0.001). In comparison to the NRS 2002 score, the mNUTRIC score demonstrated a superior prognostic ability in ECMO patients.

Evaluation of the Current State of Chatbots for Digital Health: Scoping Review.

BACKGROUND: Chatbots have become ubiquitous in our daily lives, enabling natural language conversations with users through various modes of communication. Chatbots have the potential to play a significant role in promoting health and well-being. As the number of studies and available products related to chatbots continues to rise, there is a critical need to assess product features to enhance the design of chatbots that effectively promote health and behavioral change. OBJECTIVE: This scoping review aims to provide a comprehensive assessment of the current state of health-related chatbots, including the chatbots' characteristics and features, user backgrounds, communication models, relational building capacity, personalization, interaction, responses to suicidal thoughts, and users' in-app experiences during chatbot use. Through this analysis, we seek to identify gaps in the current research, guide future directions, and enhance the design of health-focused chatbots. METHODS: Following the scoping review methodology by Arksey and O'Malley and guided by the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) checklist, this study used a two-pronged approach to identify relevant chatbots: (1) searching the iOS and Android App Stores and (2) reviewing scientific literature through a search strategy designed by a librarian. Overall, 36 chatbots were selected based on predefined criteria from both sources. These chatbots were systematically evaluated using a comprehensive framework developed for this study, including chatbot characteristics, user backgrounds, building relational capacity, personalization, interaction models, responses to critical situations, and user experiences. Ten coauthors were responsible for downloading and testing the chatbots, coding their features, and evaluating their performance in simulated conversations. The testing of all chatbot apps was limited to their free-to-use features. RESULTS: This review provides an overview of the diversity of health-related chatbots, encompassing categories such as mental health support, physical activity promotion, and behavior change interventions. Chatbots use text, animations, speech, images, and emojis for communication. The findings highlight variations in conversational capabilities, including empathy, humor, and personalization. Notably, concerns regarding safety, particularly in addressing suicidal thoughts, were evident. Approximately 44% (16/36) of the chatbots effectively addressed suicidal thoughts. User experiences and behavioral outcomes demonstrated the potential of chatbots in health interventions, but evidence remains limited. CONCLUSIONS: This scoping review underscores the significance of chatbots in health-related applications and offers insights into their features, functionalities, and user experiences. This study contributes to advancing the understanding of chatbots' role in digital health interventions, thus paving the way for more effective and user-centric health promotion strategies. This study informs future research directions, emphasizing the need for rigorous randomized control trials, standardized evaluation metrics, and user-centered design to unlock the full potential of chatbots in enhancing health and well-being. Future research should focus on addressing limitations, exploring real-world user experiences, and implementing robust data security and privacy measures.

Coverage and impact of influenza vaccination among children in Minhang District, China, 2013-2020.

Background: Young children have a great disease burden and are particularly vulnerable to influenza. This study aimed to assess the direct effect of influenza vaccination among children and to evaluate the indirect benefit of immunizing children. Methods: The influenza vaccination records for all children born during 2013-2019 in Minhang District and surveillance data for reported influenza cases were obtained from the Minhang CDC. 17,905 children were recorded in the vaccination system and included in this study. Descriptive epidemiology methods were used for data analysis, including an ecological approach to estimate the number of influenza cases averted by vaccination and linear regression to estimate the reduction in influenza cases in the general population per thousand additional childhood vaccination doses. Results: During the study period, the annual vaccination coverage rate ranged from 10.40% in 2013-2014 to 27.62% in 2015-2016. The estimated number of influenza cases averted by vaccination ranged from a low of 0.28 (range: 0.23-0.34) during 2013-2014 (PF: 6.15%, range: 5.11-7.38%) to a high of 15.34 (range: 12.38-18.51) during 2017-2018 (PF: 16.54%, range: 13.79-19.30%). When increasing vaccination coverage rate by 10% in each town/street, a ratio of 7.27-10.69% cases could be further averted on the basis of observed cases. In four selected periods, the number of influenza cases in the general population was most significantly correlated with the cumulative childhood vaccination doses in the prior 2-5 months, and the reduction in influenza cases ranged from 0.73 to 3.18 cases per thousand additional childhood vaccination doses. Conclusion: Influenza vaccination among children is estimated to have direct effects in terms of averted cases and might provide an underlying indirect benefit to the general population. Vaccination coverage in high-coverage areas should be further expanded to avert more influenza cases.

Subjective Social Mobility among Migrant Children in China.

Little scholarly attention has been paid to the relationship between children's subjective social mobility and their "social ecology". Children's subjective social mobility is about how they perceive their future social position compared to their parents'. Social ecology refers to the influential multi-layered surrounding factors, including family, school, and community. We analyzed data from structured questionnaires completed by 2221 migrant children (1296 boys and 925 girls, with a mean age of 11.7 years) from three private schools in Guangzhou and Foshan, China. The findings indicate that participants anticipated a significant improvement in their future social status. Of the factors influencing this belief, community integration has the most significant impact (TE = 0.246), followed by school integration (TE = 0.220) and family socioeconomic status (TE = 0.053). We also found that children's self-concept plays a role in their perceptions of social mobility. Based on the study results, we propose recommendations to provide migrant children additional protection and enhance their living environment.

Cav3.1-driven bursting firing in ventromedial hypothalamic neurons exerts dual control of anxiety-like behavior and energy expenditure.

The central nervous system has evolved to coordinate the regulation of both the behavior response to the external environment and homeostasis of energy expenditure. Recent studies have indicated the dorsomedial ventromedial hypothalamus (dmVMH) as an important hub that regulates both innate behavior and energy homeostasis for coping stress. However, how dmVMH neurons control neuronal firing pattern to regulate chronic stress-induced anxiety and energy expenditure remains poorly understood. Here, we found enhanced neuronal activity in VMH after chronic stress, which is mainly induced by increased proportion of burst firing neurons. This enhancement of VMH burst firing is predominantly mediated by Cav3.1 expression. Optogenetically evoked burst firing of dmVMH neurons induced anxiety-like behavior, shifted the respiratory exchange ratio toward fat oxidation, and decreased food intake, while knockdown of Cav3.1 in the dmVMH had the opposite effects, suggested that Cav 3.1 as a crucial regulator. Interestingly, we found that fluoxetine (anxiolytics) could block the increase of Cav3.1 expression to inhibit the burst firing, and then rescued the anxiety-like behaviors and energy expenditure changes. Collectively, our study first revealed an important role of Cav3.1-driven bursting firing of dmVMH neurons in the control of anxiety-like behavior and energy expenditure, and provided potential therapeutic targets for treating the chronic stress-induced emotional malfunction and metabolism disorders.

Identification and phylogenetic analysis of voltage-gated sodium channel haplotypes in the malaria vector Anopheles sinensis using a high-throughput amplicon sequencing approach.

BACKGROUND: Anopheles sinensis is a dominant vector for malaria transmission in Asian countries. Voltage-gated sodium channel (VGSC) mutation-mediated knock-down resistance (kdr) has developed in many A. sinensis populations because of intensive and long-term use of pyrethroids. Our previous study showed that multiple mutations at position 1014 of the VGSC were heterogeneously distributed in A. sinensis populations across Sichuan, China. METHODS: To understand resistance genotypes at the haplotype level and reconstruct the phylogenetic relationship of VGSC haplotypes, a cost-effective next-generation sequencing (NGS)-based amplicon sequencing approach was established to clarify haplotypes containing codon 1014 of the VGSC gene from a total of 446 adults collected in 12 locations of Sichuan, China. RESULTS: Nineteen (19) haplotypes were identified, including 11 wild 1014L, 6 resistance 1014F, and 2 resistance 1014C haplotypes. We found that resistance haplotypes of A. sinensis VGSC were widely distributed at frequencies ranging from 3.67 to 92.61%. The frequencies of the 1014C haplotype in the southeast of Sichuan (Luzhou, Guangan, and Suining) were relatively higher than those in other sampling locations. Phylogenetic analyses support that kdr-type mutation at position 1014 is not singly originated and resistance 1014C haplotypes evolve from TTT-encoding 1014F. CONCLUSIONS: A cost-effective next-generation sequencing (NGS)-based amplicon sequencing approach has been established in this study. The data revealed the patchy distribution of VGSC resistance haplotypes with overall high frequencies in Sichuan, China. Phylogenetic analyses support multiple origins and sequential evolution (1014L → 1014F → 1014C) for kdr-type mutations in A. sinensis.

Prenatal and postnatal exposure risk assessment of chlorinated paraffins in mothers and neonates: Occurrence, congener profile, and transfer behavior.

Gestation and lactation are very sensitive and vulnerable stages for human growth and development. During these two periods, short-chain chlorinated paraffins (SCCPs) and medium-chain chlorinated paraffins (MCCPs) can be transported to neonates via transplacental and breastfeeding transfers, and eventually posing potential adverse effects to neonates. Up to date, no simultaneous investigation of prenatal and postnatal exposure of CPs is reported. To bridge this knowledge gap, we have analyzed SCCPs and MCCPs in 20 complete sets of maternal serum, umbilical cord serum, placenta, and breast milk. The levels of both ∑SCCP and ∑MCCP followed the order of maternal serum > breast milk > cord serum > placenta. The breastfeeding transfer ratios (RBM, ≈ 1.0) of CPs were greater than the corresponding transplacental transfer ratios (RCM, < 1.0), demonstrating the higher transport of CPs during the lactation period. The placental retention/or accumulation ratios (RPM) showed that CPs were effectively retained by the placental barrier. Furthermore, the total exposure amount of SCCPs and MCCPs during the lactation period was> 100 times higher than the gestation exposure amounts. This study helps to better understand the prenatal and postnatal exposure of CPs and provides a solid basis for accurate human health risk assessment of CPs.

Assessing different anthropometric indices and their optimal cutoffs for prediction of type 2 diabetes and impaired fasting glucose in Asians: The Jinchang Cohort Study.

BACKGROUND: To study the association between anthropometric measurements and the risk of diabetes and impaired fasting glucose (IFG) and compare body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) to determine the best indicator and its optimal cutoffs for predicting type 2 diabetes and IFG. METHODS: A Chinese prospective (2011-2019) cohort named the Jingchang cohort that included 48 001 participants was studied. Using Cox proportional hazard models, hazard ratios (HRs) for incident type 2 diabetes or IFG per 1 SD change in BMI, WC, and WHtR were calculated. Area under the curve (AUC) was compared to identify the best anthropometric variable and its optimal cutoff for predicting diabetes. RESULTS: The association of BMI, WC, and WHtR with type 2 diabetes or IFG risk was positive in the univariate and multivariable-adjusted Cox proportional hazard models. Of all three indexes, the AUC of BMI was largest and that of WC was smallest. The derived cutoff values for BMI, WC, and WHtR were 24.6 kg/m2 , 89.5 cm, and 0.52 in men and 23.4 kg/m2 , 76.5 cm, and 0.47 in women for predicting diabetes, respectively. The derived cutoff values for BMI, WC, and WHtR were 23.4 kg/m2 , 87.5 cm, and 0.50 in men and 22.5 kg/m2 , 76.5 cm, and 0.47 in women for predicting IFG, respectively. [Correction added on 14 April 2020, after first online publication: '0' has been deleted from 'WC,0' in the first sentence.]. CONCLUSIONS: Our derived cutoff points were lower than the values specified in the most current Asian diabetes guidelines. We recommend a cutoff point for BMI in Asians of 23 kg/m2 and for WC a cutoff point of 89 cm in men and 77 cm in women to define high-risk groups for type 2 diabetes; screening should be considered for these populations.

Patient-Reported Treatment Satisfaction with Dabigatran versus Warfarin in Patients with Non-Valvular Atrial Fibrillation in China.

BACKGROUND: Anti-coagulant therapy satisfaction for patients with atrial fibrillation is a critical issue, which impacts on their treatment adherence and clinical outcomes. The disadvantages of long-term warfarin treatment are well-described, and novel oral anti-coagulants have become an alternative option. MATERIALS AND METHODS: We compared patient-reported treatment satisfaction with dabigatran versus warfarin in non-valvular atrial fibrillation (NVAF) patients in China. Treatment satisfaction was assessed using the Anti-Clot Treatment Scale (ACTS) questionnaire, which included a 12-item ACTS Burdens scale and a 3-item ACTS Benefits scale. RESULTS: Among 834 patients, 246 patients (29.5%) were taking dabigatran and the others were on warfarin. Propensity score matching was employed to identify 182 patient pairs with balanced baseline characteristics. The global ACTS Burdens score and the global ACTS Benefits score were comparable between the dabigatran and warfarin groups (44.86 ± 3.95 vs. 44.28 ± 3.51, p = 0.423; 11.49 ± 2.92 vs. 11.42 ± 3.03, p = 0.194, respectively). The monthly cost of dabigatran was significantly higher compared with that of warfarin due to a lack of insurance coverage (USD 176.78 ± 9.15 vs. USD 2.49 ± 0.76, p = 0.000). The discontinuation rate of dabigatran was significantly higher than warfarin at the 6-month follow-up (33.5% vs. 19.2%, p = 0.003). Adjusted logistic regression showed that dabigatran was associated with a significant greater odds of non-persistence (odds ratio: 2.13, 95% confidence interval: 1.27-3.59, p = 0.004). CONCLUSION: Dabigatran therapy in patients with NVAF in China associated with no improvement in satisfaction and a higher discontinuation rate compared with warfarin therapy largely due to increased economic burden.

Uptake of evidence-based statin therapy among atrial fibrillation patients in China: A report from the CAFR (Chinese Atrial Fibrillation Registry) Study.

BACKGROUND: Atrial fibrillation (AF) is associated with increased incidence of cardiovascular disease, and hence, statin therapy is indicated in majority of AF patients. METHODS AND RESULTS: We analyzed data from the Chinese Atrial Fibrillation Registry (CAFR) involving 11,496 AF patients from 2011 to 2014. Practice patterns of statin therapy and factors associated with statin underuse were analyzed. Based on the 2013 ACC/AHA cholesterol management guidelines, statins should be recommended for 67.4% (7720/11,461) of AF participants in CAFR, but only 43.4% (3352/7720) with appropriate indications were taking statins. Statin underuse in AF patients was independently associated with male sex, tertiary hospital treatment, outpatient attendance, and absence of 'high risk' cardiovascular risk factors (overweight, diabetes, coronary heart disease, stroke/transient ischemic attack/peripheral embolism and hypertension). CONCLUSIONS: A high proportion of Chinese AF patients had indications for statin therapy. Evidence-based statin prescribing was suboptimal in this population. Greater efforts should be made to improve a holistic approach to cardiovascular risk management in the Chinese AF population.

Simultaneous ureteroscopic lithotripsy and contralateral percutaneous nephrolithotomy for ureteral calculi combined with renal staghorn calculi.

OBJECTIVES: To investigate the efficacy, safety, and cost-effectiveness of simultaneous ureteroscopic lithotripsy and contralateral percutaneous nephrolithotomy for ureteral calculi combined with contralateral renal staghorn calculi. METHODS: The present prospective controlled trial had been registered with the Chinese Clinical Trial Registry (Registration number: ChiCTR-ONRC-13004146). Patients with ureteral calculi and contralateral renal staghorn calculi were enrolled into the staged (ureteroscopic lithotripsy first followed by a staged percutaneous nephrolithotomy) or the simultaneous (synchronous ureteroscopic lithotripsy and contralateral percutaneous nephrolithotomy) treatment group according to the odd or even number of the last hospitalization number. All patients signed informed consent. The primary outcomes were the stone-free rate and total hospital costs. The second outcomes were the operative and anesthesia times, the complication rate, and hospital stay. RESULTS: A total of 51 patients were enrolled into the staged group and 52 patients were enrolled into the simultaneous group. There were no statistically significant differences in patients' characteristics. The overall stone-free rate was 94.1% in the staged group and 92.3% in the simultaneous group. No severe complication was observed. The total hospital stay of the staged group was longer, and it was negatively correlated to different procedures. The cost in the staged group was higher, and it was correlated with total operation time and postoperative hospital stay. CONCLUSIONS: Simultaneous ureteroscopic lithotripsy and contralateral percutaneous nephrolithotomy represent safe and effective procedures, and they can be considered as a first-line treatment for selected patients presenting with ureteral calculi combined with contralateral renal calculi.

Weight of the CURB-65 criteria for community-acquired pneumonia in a very low-mortality-rate setting.

OBJECTIVE: The CURB-65 score is a simple well validated tool for the assessment of severity in community-acquired pneumonia (CAP). The weight of each criterion in very low-mortality-rate settings is unclear. The purpose of this study was to determine the weight in such setting. METHODS: This study retrospectively reviewed 1,230 adult patients admitted for CAP from 2005 to 2009. RESULTS: The 30-day mortality rose sharply from 0%, 1.0%, 8.2% and 16.7%, respectively, for patients with CURB-65 scores of 0, 1, 2 and 3 to 100.0% for patients with the scores of 4 (x(2) = 219.494, p<0.001). Confusion had the strongest association with mortality (odds ratio, 22.148). The presence of low blood pressure was not associated with mortality. Confusion, urea >7 mmol.L(-1) and age ≥ 65 yrs showed independent relationships with mortality (Odds ratio, 11.537, 5.988 and 10.462; respectively). Urea >7 mmol.L(-1) was most strongly associated with the sequential organ failure assessment (SOFA) scores [rank correlation coefficient (r(s)), 0.352]. Confusion had the closest relationship with hospital length of stay (r(s), 0.114). Age ≥ 65 yrs had the strongest association with costs (r(s), 0.223). Conclusion The individual CURB-65 criteria were of unequal weight for predicting the 30-day mortality, SOFA scores, hospital length of stay and costs in a very low-mortality-rate setting, and a low blood pressure was not associated with mortality.

Trafficking defects and gating abnormalities of a novel SCN5A mutation question gene-specific therapy in long QT syndrome type 3.

RATIONALE: Sodium channel blockers are used as gene-specific treatments in long-QT syndrome type 3, which is caused by mutations in the sodium channel gene (SCN5A). Response to treatment is influenced by biophysical properties of mutations. OBJECTIVE: We sought to investigate the unexpected deleterious effect of mexiletine in a mutation combining gain-of- function and trafficking abnormalities. METHODS AND RESULTS: A long-QT syndrome type 3 child experienced paradoxical QT prolongation and worsening of arrhythmias after mexiletine treatment. The SCN5A mutation F1473S expressed in HEK293 cells presented a right-ward shift of steady-state inactivation, enlarged window current, and huge sustained sodium current. Unexpectedly, it also reduced the peak sodium current by 80%. Immunostaining showed that mutant Nav1.5 is retained in the cytoplasm. Incubation with 10 micromol/L mexiletine rescued the trafficking defect of F1473S, causing a significant increase in peak current, whereas sustained current was unchanged. Using a Markovian model of the Na channel and a model of human ventricular action potential, we showed that simulated exposure of F1473S to mexiletine paradoxically increased action potential duration, mimicking QT prolongation seen in the index patient on mexiletine treatment. CONCLUSIONS: Sodium channel blockers are largely used to shorten QT intervals in carriers of SCN5A mutations. We provided evidence that these agents may facilitate trafficking of mutant proteins, thus exacerbating QT prolongation. These data suggest that caution should be used when recommending this class of drugs to carriers of mutations with undefined electrophysiological properties.

Identification of complement C3f-desArg and its derivative for acute leukemia diagnosis and minimal residual disease assessment.

Therapeutic conditions for acute leukemia (AL) mainly rely on diagnosis and detection of minimal residual disease (MRD). However, no serum biomarker has been available for clinicians to make diagnosis of AL and assessment of MRD. In this study, we performed bead fractionation/MALDI-TOF-MS analysis on sera from patients with AL. Support vector machine algorithm was used to obtain diagnostic model that discriminated proteomic spectra of patients with AL from that of controls. Twenty-six features with p<0.00001 had optimal discriminatory performance, with 97% sensitivity and 100% specificity. Statistical analysis revealed that two peptides with m/z 1778 and 1865 were gradually decreased in their relative intensities with increase of remission degree. Moreover, the peptide with m/z 1865 was also found to be correlated with AL types. With FT-ICR-MS detection, both the peptides were identified as fragments of complement C3f. Linear regression analysis showed that the combined use of them could discriminate PML/RAR alpha positive M3 from molecular remission M3. Two fragments of complement C3f were significantly correlated with MRD levels and could be used for clinical practice in MRD assessment.