A benchmark for machine-learning based non-invasive blood pressure estimation using photoplethysmogram.

Blood Pressure (BP) is an important cardiovascular health indicator. BP is usually monitored non-invasively with a cuff-based device, which can be bulky and inconvenient. Thus, continuous and portable BP monitoring devices, such as those based on a photoplethysmography (PPG) waveform, are desirable. In particular, Machine Learning (ML) based BP estimation approaches have gained considerable attention as they have the potential to estimate intermittent or continuous BP with only a single PPG measurement. Over the last few years, many ML-based BP estimation approaches have been proposed with no agreement on their modeling methodology. To ease the model comparison, we designed a benchmark with four open datasets with shared preprocessing, the right validation strategy avoiding information shift and leak, and standard evaluation metrics. We also adapted Mean Absolute Scaled Error (MASE) to improve the interpretability of model evaluation, especially across different BP datasets. The proposed benchmark comes with open datasets and codes. We showcase its effectiveness by comparing 11 ML-based approaches of three different categories.

A leading bibliometric author does not have a dominant contribution to research based on the CJAL score: Bibliometric analysis.

BACKGROUND: A total of 22,367 bibliometric articles have been indexed by Web of Science (WoS). The most significant contribution to the field has not yet been identified through bibliometric analysis. A comparison of individual research achievements (IRAs) and trend analysis of article citations are required after extracting bibliometric articles. The study aimed to confirm whether the leading author has a dominant RA and which articles are worth reading for readers using trend analysis. METHODS: We identified authors with at least 100 articles related to bibliometrics in the WoS core collection. A total of 399 articles were collected to cluster author collaborations. Co-word analysis and chord diagrams were used to match chief authors in clusters with Keywords Plus in WoS core collection. The category, journal impact factor, authorship, and L-index (CJAL) score and the absolute advantage coefficient (AAC) were used to compare IRAs and identify the leading author who dominated the field significantly beyond the next 2 authors. In addition to network charts and chord diagrams, 4 visualizations were used to report study results, including a Sankey diagram, a dot plot, a temporal trend graph, and a radar plot. The temporal bubble graph was used to select articles that deserve to be read. RESULTS: The top 3 authors were Lutz Bornmann, Yuh-Shan Ho, and Giovanni Abramo, with CJAL scores of 176.22, 176.02, and 112.06, respectively, from Germany, Italy, and Taiwan. Based on the weak dominance coefficient (AAC = 0.20 < 0.70), it is evident that the leading bibliometric author has no such significant power beyond the next 2 leading authors in IRAs. A trend analysis of the last 4 years was used to illustrate the 2 articles that deserve to be read. CONCLUSION: Three leading authors were identified through a co-word analysis of bibliometrics. There was no evidence of an author who possessed a dominant position due to a lower AAC on the leading author. The CJAL score and the AAC can be applied to many bibliographical studies in the future rather than being limited to bibliometric studies that evaluate the leading authors in a field, as we did in this study.

Bilateral theta-burst stimulation on emotional processing in major depressive disorder: A functional neuroimaging study from a randomized, double-blind, sham-controlled trial.

AIM: Bilateral theta-burst stimulation (biTBS; intermittent TBS over the left dorsolateral prefrontal cortex [DLPFC] and continuous TBS over the right DLPFC) has demonstrated efficacy in improving symptoms in patients with major depressive disorder (MDD). However, the underlying brain mechanisms remain unknown. The authors aimed to investigate the antidepressant efficacy of biTBS monotherapy and its effects on the brain responses measured by functional magnetic resonance imaging (fMRI) during emotional processing in MDD. METHODS: The authors conducted a double-blind, randomized, sham-controlled trial of patients with MDD who exhibited no responses to at least one adequate antidepressant treatment for the prevailing episode. Recruited patients were randomly assigned to 10 biTBS monotherapy or sham stimulation sessions. The fMRI scans during performing emotional recognition task were obtained at baseline and after 10 sessions of treatment. Depressive symptoms were assessed using the 21-item Hamilton Rating Scale for Depression at baseline and the weeks 4, 8, 12, 16, 20, and 24 week. RESULTS: The biTBS group (n = 17) exhibited significant decreases in depression scores compared with the sham group (n = 11) at week 8 (70% vs 40%; P = 0.02), and the significant differences persisted during the 24-week follow-up periods. At week 4, when the treatment course was completed, patients in the biTBS group, but not in the sham group, exhibited increased brain activities over the left superior and middle frontal gyrus during negative emotional stimuli. CONCLUSION: The authors' findings provide the first evidence regarding the underlying neural mechanisms of biTBS therapy to improve clinical symptoms in patients with MDD.

The 100 most cited articles have fewer citations than other bibliometric articles: A pairwise comparison using a temporal bubble graph.

BACKGROUND: More than 400 articles with the title of 100 top-cited articles (Top100) have been published in PubMed. It is unknown whether their citations are fewer (or more) than those found in other bibliometric studies (Nontop100). After determining article themes using coword analysis, a temporal bubble graph (TBG) was used to verify the hypothesis that the Top100 had fewer citations than the Nontop100. METHODS: Using the Web of Science core collection, the top 50 most cited articles were compiled by Top100 and Nontop100, respectively, based on the research area of biomedicine and bibliometrics only. Coword analysis was used to extract themes. The study results were displayed using 6 different visualizations, including charts with bars, pyramids, forests, clusters, chords, and bubbles. Mean citations were compared between Top100 and Nontop100 using the bootstrapping method. RESULTS: There were 18 citations in total for the 2 sets of the 50 most cited articles (range 1-134; 5 and 26.5 for Top100 and Nontop100, respectively). A significant difference in mean citations was observed between the 2 groups of Top100 and Nontop100 based on the bootstrapping method (3, 95% confidence interval: [1.18, 4.82]; 26.5, 95% confidence interval: [23.82, 29.18], P < .001). The 11 themes were clustered using coword analysis and applied to a TBG, which is composed of 4 dimensions: themes, years, citations and groups of articles. Among the 2 groups, the majority of articles were published in the journal of Medicine (Baltimore), with 9 and 7, respectively. CONCLUSION: Eleven themes were identified as a result of this study. In addition, it reveals distinct differences between the 2 groups of Top100 and Nontop100, with the former containing more recently published articles and the latter containing more citations for articles. Clinical and research clinicians and researchers can use bibliometric analysis to appraise published literature and to understand the scientific landmark using TBG in bibliometrics.

Behavior Score-Embedded Brain Encoder Network for Improved Classification of Alzheimer Disease Using Resting State fMRI.

The ability to accurately detect onset of dementia is important in the treatment of the disease. Clinically, the diagnosis of Alzheimer Disease (AD) and Mild Cognitive Impairment (MCI) patients are based on an integrated assessment of psychological tests and brain imaging such as positron emission tomography (PET) and anatomical magnetic resonance imaging (MRI). In this work using two different datasets, we propose a behavior score-embedded encoder network (BSEN) that integrates regularly adminstrated psychological tests information into the encoding procedure of representing subject's resting-state fMRI data for automatic classification tasks. BSEN is based on a 3D convolutional autoencoder structure with contrastive loss jointly optimized using behavior scores from Mini-Mental State Examination (MMSE) and Clinical Dementia Rating (CDR). Our proposed classification framework of using BSEN achieved an overall recognition accuracy of 59.44% (3-class classification: AD, MCI and Healthy Control), and we further extracted the most discriminative regions between healthy control (HC) and AD patients.

Predicting Performances on Processing and Memorizing East Asian Faces from Brain Activities in Face-Selective Regions: A Neurocomputational Approach.

For more than two decades, a network of face-selective brain regions has been identified as the core system for face processing, including occipital face area (OFA), fusiform face area (FFA), and posterior region of superior temporal sulcus (pSTS). Moreover, recent studies have suggested that the ventral route of face processing and memory should end at the anterior temporal lobes (i.e., vATLs), which may play an important role bridging face perception and face memory. It is not entirely clear, however, the extent to which neural activities in these face-selective regions can effectively predict behavioral performance on tasks that are frequently used to investigate face processing and face memory test that requires recognition beyond variation in pose and lighting, especially when non-Caucasian East Asian faces are involved. To address these questions, we first identified during a functional scan the core face network by asking participants to perform a one-back task, while viewing either static images or dynamic videos. Dynamic localizers were effective in identifying regions of interest (ROIs) in the core face-processing system. We then correlated the brain activities of core ROIs with performances on face-processing tasks (component, configural, and composite) and face memory test (Taiwanese Face Memory Test, TFMT) and found evidence for limited predictability. We next adopted an multi-voxel pattern analysis (MVPA) approach to further explore the predictability of face-selective brain regions on TFMT performance and found evidence suggesting that a basic visual processing area such as calcarine and an area for structural face processing such as OFA may play an even greater role in memorizing faces. Implications regarding how differences in processing demands between behavioral and neuroimaging tasks and cultural specificity in face-processing and memory strategies among participants may have contributed to the findings reported here are discussed.

Virtual reality video promotes effectiveness in advance care planning.

BACKGROUND: In 2019, the Patient Autonomy Act went into effect, allowing Taiwanese citizens to establish legal advance decisions. In an effort to secure a more realistic and accurate perception of situations, a virtual reality video was developed by the palliative care team of Chi-Mei hospital in southern Taiwan for citizens to use before advance care planning. This study explores the change in participants' preference and certainty regarding end-of-life decisions after using this tool. METHODS: Participants were at least 20 years old and capable of reading and understanding the information provided in the written handout with information about the legal process of making an advance decision. They completed pre-test questionnaires, viewed a six-minute 360-degree virtual reality video on a portable headset, and then completed a post-test questionnaire about their preference on the five medical options-CPR, life-sustaining treatments, antibiotics, blood transfusion, and artificial nutrition and hydration-followed by feedback on the helpfulness of the virtual reality. The control group included 40 participants who only read the handout and completed pre-test and post-test questionnaires. RESULTS: After viewing the virtual reality video, preference for not using CPR, life-sustaining treatment, antibiotics, blood transfusion, and artificial nutrition and hydration increased significantly in the virtual reality intervention group. Uncertainty regarding the five medical options mentioned above significantly decreased. The intervention was generally recognized by participants for its help in making decisions. DISCUSSION: The decrease in the number of participants who could not make decisions indicates that the virtual reality video may be helpful for users in making end-of-life decision. According to feedback, the virtual reality video helped equip users with better understanding of medical scenarios, and that it is a good decision tool for advance care planning. CONCLUSION: This is the first study since the Patient Autonomy Act has been passed that explores the effectiveness of using a virtual reality video as a decision tool in advance care planning and reveals decreased preference of CPR, life sustaining treatment, antibiotics, blood transfusion, and artificial nutrition and hydration after intervention. This decision aid proved to be an effective tool for clarifying their end-of-life care preferences.

Antidepressant efficacy and immune effects of bilateral theta burst stimulation monotherapy in major depression: A randomized, double-blind, sham-controlled study.

Inflammation theory has been consolidated by accumulating evidence, and many studies have suggested that the peripheral cytokine levels could be biomarkers for disease status and treatment outcome in major depressive disorder (MDD). Theta burst stimulation (TBS), a new form of repetitive transcranial magnetic stimulation (TMS) for MDD, has been demonstrated to improve depression via modulating dysfunctional neural network or hypothalamic­pituitary­adrenal axis hyperactivities in MDD. However, there is lack of exploratory studies investigating its effect on serum inflammatory cytokines. Here, we aimed to investigate the antidepressant efficacy of bilateral TBS monotherapy and its effects on the serum cytokine levels in MDD. We conducted a double-blind, randomized, sham-controlled trial, with 53 MDD patients who exhibited no responses to at least one adequate antidepressant treatment for the prevailing episode assigned randomly to one of two groups: bilateral TBS monotherapy (n = 27) or sham stimulation (n = 26). The TBS treatment period was 22 days. Blood samples from 31 study subjects were obtained for analyses. The bilateral TBS group exhibited significantly greater decreases in depression scores than the sham group at week 4 (56.5% vs. 33.1%; p < 0.001 [effect size (Cohen ' s d) = 1.00]) and during the 20-week follow-up periods. Significantly more responders were also found at week 4 (70.3% vs. 23.1%, p = 0.001) and during the 20-week follow-up periods. However, we did not detect any significant effects of TBS on the cytokine panels or any correlations between improvement in depressive symptoms and changes in serum inflammatory markers. Our findings provided the first evidence that the antidepressant efficacy of bilateral TBS monotherapy might not work via immune-modulating mechanisms.

Whether productive authors using the national health insurance database also achieve higher individual research metrics: A bibliometric study.

BACKGROUND: Many researchers use the National Health Insurance Research Database (HIRD) to publish medical papers and gain exceptional outputs in academics. Whether they also obtain excellent citation metrics remains unclear. METHODS: We searched the PubMed database (http://www.ncbi.nlm.nih.gov/pubmed) using the terms Taiwan and HIRD. We then downloaded 1997 articles published from 2012 to 2016. An authorship-weighted scheme (AWS) was applied to compute coauthor partial contributions from the article bylines. Both modified x-index and author impact factor (AIF) proved complementary to Hirsch's h-index for calculating individual research achievements (IRA). The metrics from 4684 authors were collected for comparison. Three hundred eligible authors with higher x-indexes were located and displayed on Google Maps dashboards. Ten separate clusters were identified using social network analysis (SNA) to highlight the research teams. The bootstrapping method was used to examine the differences in metrics among author clusters. The Kano model was applied to classify author IRAs into 3 parts. RESULTS: The most productive author was Investigator#1 (Taichung City, Taiwan), who published 149 articles in 2015 and included 803 other members in his research teams. The Kano diagram results did not support his citation metrics beyond other clusters and individuals in IRAs. CONCLUSION: The AWS-based bibliometric metrics make individual weighted research evaluations possible and available for comparison. The study results of productive authors using HIRD did not support the view that higher citation metrics exist in specific disciplines.

Lower Urinary Tract Symptoms Are Associated with Increased Risk of Dementia among the Elderly: A Nationwide Study.

Studies show a strong association between dementia and lower urinary tract symptoms (LUTS). The aim of this study was to investigate whether LUTS are a risk factor for cognitive impairment. We enrolled 50-year-old and older subjects with LUTS (LUTS([+])) (n = 6801) and controls without LUTS (LUTS([-])) (n = 20,403) from Taiwan's National Health Insurance Research Database. LUTS, dementia, and other confounding factors are defined by International Classification of Diseases, Ninth Revision, Clinical Modification Codes. Participants were recruited from 2000 to 2004 and then followed up until death or the end of 2011. The outcome was the onset of dementia, which was assessed using Poisson regression analysis, Cox hazards models, and Kaplan-Meier survival curves. The incidence of dementia was significantly higher in the LUTS([+]) group than in the LUTS([-]) group (124.76 versus 77.59/1000 person-years). The increased risk of dementia related to LUTS remained significant after adjustment for potential confounders (adjusted hazard ratio (AHR): 1.61, 95% confidence interval (CI) 1.47-1.76, P < 0.0001) and higher than that related to cerebrovascular disease (AHR: 1.43, 95% CI 1.26-1.61, P < 0.0001). The outcome suggests the need for early screening and appropriate intervention to help prevent cognitive impairment of patients with LUTS.

Measuring interactions between polydimethylsiloxane and serum proteins at the air-water interface.

The interaction between synthetic polymers and proteins at interfaces is relevant to basic science as well as a wide range of applications in biotechnology and medicine. One particularly common and important interface is the air-water interface (AWI). Due to the special energetics and dynamics of molecules at the AWI, the interplay between synthetic polymer and protein can be very different from that in bulk solution. In this paper, we applied the Langmuir-Blodgett technique and fluorescence microscopy to investigate how the compression state of polydimethylsiloxane (PDMS) film at the AWI affects the subsequent adsorption of serum protein [e.g., human serum albumin (HSA) or immunoglobulin G (IgG)] and the interaction between PDMS and protein. Of particular note is our observation of circular PDMS domains with micrometer diameters that form at the AWI in the highly compressed state of the surface film: proteins were shown to adsorb preferentially to the surface of these circular PDMS domains, accompanied by a greater than 4-fold increase in protein found in the interfacial film. The PDMS-only film and the PDMS-IgG composite film were transferred to cover glass, and platinum-carbon replicas of the transferred films were further characterized by scanning electron microscopy and atomic force microscopy. We conclude that the structure of the PDMS film greatly affects the amount and distribution of protein at the interface.

Lipid sorting by ceramide structure from plasma membrane to ER for the cholera toxin receptor ganglioside GM1.

The glycosphingolipid GM1 binds cholera toxin (CT) on host cells and carries it retrograde from the plasma membrane (PM) through endosomes, the trans-Golgi (TGN), and the endoplasmic reticulum (ER) to induce toxicity. To elucidate how a membrane lipid can specify trafficking in these pathways, we synthesized GM1 isoforms with alternate ceramide domains and imaged their trafficking in live cells. Only GM1 with unsaturated acyl chains sorted efficiently from PM to TGN and ER. Toxin binding, which effectively crosslinks GM1 lipids, was dispensable, but membrane cholesterol and the lipid raft-associated proteins actin and flotillin were required. The results implicate a protein-dependent mechanism of lipid sorting by ceramide structure and provide a molecular explanation for the diversity and specificity of retrograde trafficking by CT in host cells.

Curvature sorting of peripheral proteins on solid-supported wavy membranes.

Cellular membrane deformation and the associated redistribution of membrane-bound proteins are important aspects of membrane function. Current model membrane approaches for studying curvature sensing are limited to positive curvatures and often require complex and delicate experimental setups. To overcome these challenges, we fabricated a wavy substrate by imposing a range of curvatures onto an adhering lipid bilayer membrane. We examined the curvature sorting of several peripheral proteins binding to the wavy membrane and observed them to partition into distinct regions of curvature. Furthermore, single-molecule imaging experiments suggested that the curvature sensing of proteins on low-curvature substrates requires cooperative interactions.

Ligand mobility modulates immunological synapse formation and T cell activation.

T cell receptor (TCR) engagement induces clustering and recruitment to the plasma membrane of many signaling molecules, including the protein tyrosine kinase zeta-chain associated protein of 70 kDa (ZAP70) and the adaptor SH2 domain-containing leukocyte protein of 76 kDa (SLP76). This molecular rearrangement results in formation of the immunological synapse (IS), a dynamic protein array that modulates T cell activation. The current study investigates the effects of apparent long-range ligand mobility on T cell signaling activity and IS formation. We formed stimulatory lipid bilayers on glass surfaces from binary lipid mixtures with varied composition, and characterized these surfaces with respect to diffusion coefficient and fluid connectivity. Stimulatory ligands coupled to these surfaces with similar density and orientation showed differences in their ability to activate T cells. On less mobile membranes, central supramolecular activation cluster (cSMAC) formation was delayed and the overall accumulation of CD3ζ at the IS was reduced. Analysis of signaling microcluster (MC) dynamics showed that ZAP70 MCs exhibited faster track velocity and longer trajectories as a function of increased ligand mobility, whereas movement of SLP76 MCs was relatively insensitive to this parameter. Actin retrograde flow was observed on all surfaces, but cell spreading and subsequent cytoskeletal contraction were more pronounced on mobile membranes. Finally, increased tyrosine phosphorylation and persistent elevation of intracellular Ca(2+) were observed in cells stimulated on fluid membranes. These results point to ligand mobility as an important parameter in modulating T cell responses.

Cyano analogues of 7-azaindole: probing excited-state charge-coupled proton transfer reactions in protic solvents.

The interplay between excited-state charge and proton transfer reactions in protic solvents is investigated in a series of 7-azaindole (7AI) derivatives: 3-cyano-7-azaindole (3CNAI), 5-cyano-7-azaindole (5CNAI), 3,5-dicyano-7-azaindole (3,5CNAI) and dicyanoethenyl-7-azaindole (DiCNAI). Similar to 7AI, 3CNAI and 3,5CNAI undergo methanol catalyzed excited-state double proton transfer (ESDPT), resulting in dual (normal and proton transfer) emission. Conversely, ESDPT is prohibited for 5CNAI and DiCNAI in methanol, as supported by a unique normal emission with high quantum efficiency. Instead, the normal emission undergoes prominent solvatochromism. Detailed relaxation dynamics and temperature dependent studies are carried out. The results conclude that significant excited-state charge transfer (ESCT) takes place for both 5CNAI and DiCNAI. The charge-transfer specie possesses a different dipole moment from that of the proton-transfer tautomer species. Upon reaching the equilibrium polarization, there exists a solvent-polarity induced barrier during the proton-transfer tautomerization, and ESDPT is prohibited for 5CNAI and DiCNAI during the excited-state lifespan. The result is remarkably different from 7AI, which is also unique among most excited-state charge/proton transfer coupled systems studied to date.

Excited-state double proton transfer in model base pairs: the stepwise reaction on the heterodimer of 7-azaindole analogues.

A four fused-ring system 11-propyl-6H-indolo[2,3-b]quinoline (6 HIQ) is strategically designed and synthesized; it possesses a central moiety of 7-azaindole (7AI) and undergoes excited-state double proton transfer (ESDPT). Despite a barrierless type of ESDPT in the 6 HIQ dimer, femtosecond dynamics and a kinetic isotope effect provide indications for a stepwise ESDPT process in the 6 HIQ/7AI heterodimer, in which 6 HIQ (deuterated 6 HIQ) delivers the pyrrolyl proton (deuteron) to 7AI (deuterated 7AI) in less than 150 fs, forming an intermediate with a charge-transfer-like ion pair, followed by the transfer of a pyrrolyl proton (deuteron) from cation-like 7AI (deuterated 7AI) to the pyridinyl nitrogen of the anion-like 6 HIQ (deuterated 6 HIQ) in approximately 1.5+/-0.3 ps (3.5+/-0.3 ps). The barrier of second proton transfer is estimated to be 2.86 kcal mol(-1) for the 6 HIQ/7AI heterodimer.

Synthesis, structure and electroluminescent properties of cyclometalated iridium complexes possessing sterically hindered ligands.

New CN donor ligands incorporating pyridine or benzoimidazole N donors and a sterically hindered cyclometalating aromatic core featuring a polyphenylenephenyl, fluoranthene, or triphenylene segment are prepared and successfully converted into heteroleptic iridium(III) cyclometalated complexes with acetylacetone auxiliary ligands. The X-ray structure of the complex, derived from a ligand containing a fluoranthene fragment, has been solved to unveil the corresponding structure. The results clearly demonstrate that the nature of the sigma-coordinating ligand segment plays a key role in dictating the emission profile and peak position, such that the emission hue has been successfully tuned ranging from green to red. Supplementary support of this viewpoint is also rendered by computational (DFT) approaches. Electroluminescent devices fabricated using a complex as dopant in the PVK matrix were found to exhibit bright greenish yellow emission with promising device characteristics (maximum brightness 26450 cd m(-2) at 30 V and a maximum current efficiency of 40 cd A(-1)).

7-Azamelatonin: efficient synthetic routes, excited-state double proton transfer properties and biomedical implications.

On the basis of a seven-step synthetic route, the total synthesis of 7-azamelatonin, an analogue of melatonin, has been achieved with an overall yield of approximately 9.2%. In aqueous solution, 7-azamelatonin exhibits a unique excited-state double proton transfer (ESDPT) property, resulting in dual emission bands (405 and 560 nm). The ESDPT property makes 7-azamelatonin superb as a potential molecular probe for future bioapplication and for pharmacological research.

Synthesis of 7-azaserotonin: its photophysical properties associated with excited state proton transfer reaction.

We report the synthesis of 3-(2-aminoethyl)-5-ol-1H-pyrrolo[2,3-b]pyridine (7-azaserotonin), which may potentially serve as an agonist or antagonist of serotonin receptors. In alcohols, the solvent (e.g., ethanol) catalyzed proton-transfer reaction takes place for 7-azaserotonin in the excited state, resulting in dual emission. Conversely, excited-state deprotonation takes place in neutral aqueous solution. The unique excitation behavior makes 7-azaserotonin versatile as a potential bioprobe.