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Tzu-Lin Yeh,1 Pei-Ching Shih,1 Shu-Jung Liu,2 Chao-Hsu Lin,3 Jui-Ming Liu,4,5 Wei-Te Lei,3,* Chien-Yu Lin3,* 1Department of Family Medicine, Hsinchu MacKay Memorial Hospital, Hsinchu, 2Department of Medical Library, MacKay Memorial Hospital, Tamsui Branch, New Taipei City, 3Department of Pediatrics, Hsinchu MacKay Memorial Hospital, Hsinchu, 4Department of Surgery, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, 5Department of Medicine, National Yang-Ming University, Taipei, Taiwan *These authors contributed equally to this work Background: Influenza infection is a common disease with a huge disease burden. Influenza vaccination has been widely used, but concerns regarding vaccine efficacy exist, especially in the elderly. Probiotics are live microorganisms with immunomodulatory effects and may enhance the immune responses to influenza vaccination. Methods: We conducted a systematic review and meta-analysis to determine the influence of prebiotics/probiotics/synbiotics supplementation on vaccine responses to influenza vaccination. Studies were systematically identified from electronic databases up to July 2017. Information regarding study population, influenza vaccination, components of supplements, and immune responses were extracted and analyzed. Twelve studies, investigating a total of 688 participants, were included in this review. Results: Patients with prebiotics/probiotics supplements were found to have higher influenza hemagglutination inhibition antibody titers after vaccination (for A/H1N1, 42.89 vs 35.76, mean difference =7.14, 95% CI =2.73, 11.55, P=0.002; for A/H3N2, 105.4 vs 88.25, mean difference =17.19, 95% CI =3.39, 30.99, P=0.01; for B strain, 34.87 vs 30.73, mean difference =4.17, 95% CI =0.37, 7.96, P=0.03).Conclusion: Supplementation with prebiotics or probiotics may enhance the influenza hemagglutination inhibition antibody titers in all A/H1N1, A/H3N2, and B strains (20%, 19.5%, and 13.6% increases, respectively). Concomitant prebiotics or probiotics supplementation with influenza vaccination may hold great promise for improving vaccine efficacy. However, high heterogeneity was observed and further studies are warranted. Keywords: influenza, influenza vaccine, probiotics, prebiotics, synbiotics, antibody titer, immune response

There is great interest in the relationships between memory span tasks and cognitive abilities. However, the causes underlying their correlation remain unknown. In the present article, five key data sets were reanalyzed according to two criteria: They must consider complex span tasks (so-called working memory [WM] tasks) and simple span tasks (so-called short-term memory [STM] tasks), and they must comprise cognitive ability measures. The obtained results offer several points of interest. First, memory span tasks should be conceived from a hierarchical perspective: They comprise both general and specific components. Second, the general component explains about four times the variance explained by the specific components. Third, STM and WM measures are closely related. Fourth, STM and WM measures share the same common variance with cognitive abilities. Finally, the strong relationship usually found between memory span tasks and cognitive abilities could be tentatively interpreted by the component shared by STM and WM--namely, the capacity for temporarily preserving a reliable memory representation of any given information. [ABSTRACT FROM AUTHOR]

Introduction: Dementia and mild cognitive impairment (MCI) present both health and economic challenges on a global scale, thus affecting millions of people, and is projected to increase significantly by the year 2050. Early language processing deficits are evident in those diagnosed with Alzheimer's disease and MCI. Recent advances in pharmacologic and non-pharmacologic interventions, including cognitive rehabilitation and training, show promising effects on cognitive functions. Articulation training, particularly, is highlighted for its potential in addressing the communication difficulties which those experiencing dementia and MCI face, based on the transmission deficit hypothesis. This study aimed to perform a voxel-wise comparison of morphological changes in grey matter volume as well as white matter integrity to represent the plastic changes in response to articulation training among older, healthy Japanese adults., Methods: Forty older, healthy Japanese adults were randomized into either a cognitive training group or a control group. The study involved comprehensive behavioral assessments, neuroimaging (including 3D anatomy, fMRI and Diffusion Tensor Imaging), and a structured verbal articulation training regimen. The training included reading tasks which focused on enhancing both articulation and phonological skills. Neuroimaging data were acquired using a 3 Tesla Siemens MR scanner, with the FSL tool being used for white matter analysis and the CAT12 toolbox for grey matter analysis., Results: Significant increases in grey matter volume were observed in certain regions, including the left Supplementary motor area, Postcentral gyrus, and bilateral Superior frontal gyrus among those in the training group. Correlations were noted between reading abilities and cortical volume in areas such as the left Middle temporal gyrus, pulvinar, and Middle occipital gyrus. White matter integrity also improved, as evidenced by increased fractional anisotropy in tracts such as the superior longitudinal fasciculus, corona radiata, and internal capsule. These findings suggest a link between articulation training and enhanced neuroplasticity in both grey and white matter regions related to language processing., Conclusion: The study demonstrates that a 4-week verbal articulation training intervention period can lead to significant improvements in grey matter volume in the left Supplementary motor area, the left Postcentral gyrus, and the bilateral Superior frontal gyrus, as well as the integrity of white matter tracts associated with language processing among older adults. These results suggest that such training could be a valuable tool in enhancing cognitive functions related to language in older populations., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: With the increasing integration of Artificial Intelligence (AI) into various aspects of daily life, there is a growing interest among designers and practitioners in incorporating AI into their fields. In healthcare domains like art therapy, AI is also becoming a subject of exploration. However, the use of AI in art therapy is still undergoing investigation, with its benefits and challenges being actively explored., Objective: This study aims to investigate the integration of AI into art therapy practices to comprehend its potential impact on therapeutic processes and outcomes. Specifically, the focus is on understanding the perspectives of art therapists regarding the utilization of AI-assisted tools in their practice with clients, as demonstrated through the presentation of our prototype consisting of a deck of cards with words covering various categories alongside an AI-generated image., Methods: Employing a co-design approach, ten art therapists affiliated with the American Art Therapy Association participated in this study. They engaged in individual interviews where they discussed their professional perspectives on integrating AI into their therapeutic approaches, evaluating the prototype. Qualitative analysis was conducted to derive themes and insights from these sessions., Results: The study began in August 2023, with data collection involving 10 participants taking place in October 2023. Our qualitative findings provide a comprehensive evaluation of the impact of AI on facilitating therapeutic processes. The combination of a deck of cards and the utilization of an AI-generated tool demonstrated an enhancement in the quality and accessibility of therapy sessions. However, challenges such as credibility and privacy concerns were also identified., Conclusions: The integration of AI into art therapy presents promising avenues for innovation and progress within the field. By gaining insights into the perspectives and experiences of art therapists, this study contributes knowledge for both practical application and further research.

To investigate the incidence of the discontinuation among tofacitinib and biologic disease-modifying anti-rheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA). This retrospective population-based cohort study included 5,008 RA patients who initiated treatment with either tofacitinib or bDMARDs (etanercept, adalimumab, golimumab, tocilizumab, or abatacept) between January 1, 2014, and December 31, 2020. We conducted Cox proportional hazards regression and subsequent time-dependent regression to assess the risk of drug discontinuation, with adjustments for potential variables. The highest drug discontinuation rate was observed with etanercept (43.27%), while the lowest was with tofacitinib (21.8%). Tofacitinib was associated with a significantly lower risk of discontinuation compared to etanercept (HR: 0.67, 95% CI: 0.57-0.80) and other bDMARDs. Higher steroid dosage and the presence of concomitant connective tissue diseases were significant risk factors for drug discontinuation. Conversely, the use of methotrexate was associated with a reduced risk of discontinuation. Tofacitinib demonstrated a lower risk of drug discontinuation compared to TNFi, with the risk factors for discontinuation including higher steroid dosage and concomitant connective tissue diseases. The study highlights the importance of considering several potential risk factors in drug discontinuation. Key Points • Non-TNFi biologic agents demonstrated better drug retention than TNFi among patients diagnosed with rheumatoid arthritis, with tofacitinib showing the lowest discontinuation rate (21.8%), underscoring its potential for superior drug retention in rheumatoid arthritis management. • Several factors were associated with drug discontinuation: higher steroid dosage and concomitant connective tissue diseases were linked to a higher discontinuation rate, whereas the concomitant use of methotrexate was associated with a lower risk of discontinuation., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Background and Purpose: Scientists have been exploring anti-angiogenic strategies to inhibit angiogenesis and prevent tumor growth. Vasculogenic mimicry (VM) in glioblastoma multiforme (GBM) poses a challenge, complicating anti-angiogenesis therapy. A novel drug, GN25 (3-[{1,4-dihydro-5,8-dimethoxy-1,4-dioxo-2-naphthalenyl}thio]-propanoic acid), can inhibit tumor formation. This study aims to investigate the microenvironmental effects and molecular mechanisms of GN25 in anti-angiogenesis and anti-VM., Experimental Approach: MTT (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) assay was used to evaluate the cell viability of different concentrations of GN25 in human umbilical vein endothelial cells (HUVEC) and Uppsala 87 malignant glioma (U87MG) cells. Functional assays were used to investigate the effects of GN25 on angiogenesis-related processes, whereas gelatin zymography, enzyme-linked immunosorbent assays, and Western blotting were utilized to assess the influence on matrix metalloproteinase (MMP)-2 and vascular endothelial growth factor (VEGF) secretion and related signaling pathways., Key Results: GN25 suppressed migration, wound healing, and tube formation in HUVECs and disrupted angiogenesis in a rat aorta ring and zebrafish embryo model. GN25 dose-dependently reduced phosphatidylinositol 3-kinase/AKT and inhibited MMP-2/VEGF secretion in HUVECs. In U87MG cells, GN25 inhibited migration, wound healing, and VM, accompanied by a decrease in MMP-2 and VEGF secretion. The results indicate that GN25 effectively inhibits angiogenesis and VM formation in HUVECs and U87MG cells without affecting preexisting vascular structures., Conclusion and Implications: This study elaborated GN25's potential as an anti-angiogenic agent by elucidating its inhibitory effects on classical angiogenesis. VM provides valuable insights for developing novel therapeutic strategies against tumor progression and angiogenesis-related diseases. These results indicate the potential of GN25 as a promising candidate for angiogenesis-related diseases., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The goal of this study is to investigate the association between chronic non-cancer pain (CNCP) and mild cognitive impairment (MCI)/Alzheimer's disease and related dementias (ADRDs) development among adults aged ≥50 using administrative claims data from a national commercial health insurance company during 2007-2017. To reduce selection bias, propensity-score matching was applied to select comparable CNCP and non-CNCP patients. Time-dependent Cox proportional-hazards regressions were conducted to estimate the hazard ratios (HRs) of incident MCI/ADRDs. Of 170,900 patients with/without CNCP, 0.61% developed MCI and 2.33% had been diagnosed with ADRDs during the follow-up period. Controlling for potential confounders, CNCP patients had a 123% increase in MCI risk (HR = 2.23; 95% CI = 1.92-2.58) and a 44% increase in ADRDs risk (HR = 1.44; 95% CI = 1.34-1.54) relative to non-CNCP patients. CNCP is a risk factor for MCI/ADRDs. Promoting awareness and improving early CNCP diagnosis in middle-aged and older adults should be incorporated into cognitive impairment and dementia prevention., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: Immature platelet fraction (IPF) for differentiating bacteremia has been explored, whereas its prognostic correlation remains uncertain. This study aims to confirm the predictive capability of IPF for bacteremia and investigate its association with prognosis., Methods: Patients with complete blood count (CBC) on the blood culture day (D1) and the preceding day (D0) were retrospectively recruited and categorized into bacteremia and nonbacteremia groups. Immature platelet (IP) analysis, alongside CBC, was conducted. Delta IPF, defined by the absolute values of D1 minus D0 results was calculated. The ability to distinguish bacteremia from nonbacteremia patients, and the correlation with mortality were analyzed., Results: From February to December 2020, a total of 150 patients were enrolled, with 75 having bacteremia. The specificity for delta IPF ≥3.4% to predict bacteremia was 97.3% (95% confidence interval [CI]: 90.7-99.7). When delta IPF ≥3.4% combined with procalcitonin ≥0.5 (ng/mL), the sensitivity was 90.5% (95% CI: 69.6%-98.8%). Within the bacteremia group, delta IPF and the proportion of patients with delta IPF ≥1.5% were significantly higher in nonsurvival, while delta platelet levels did not. Furthermore, delta IPF ≥1.5% was independently associated with 30-day mortality (adjusted odds ratio: 3.88, 95% CI: 1.2%-11.4%; p = 0.020). The 30-day survival curve demonstrated a significant difference between patients with delta IPF ≥1.5% and those without (p < 0.001)., Conclusions: Delta IPF correlates with mortality in bacteremia patients. Our findings suggest IPF not only helps detect bacteremia but also predicts prognosis in the early stage., (© 2024 John Wiley & Sons Ltd.)

Rheumatoid arthritis is a chronic inflammatory disease, and interstitial lung disease is one of the important extra-articular manifestations. There is limited evidence comparing abatacept (ABA) and tumor necrosis factor inhibitors (TNFi) regarding the risk of mortality among patients with rheumatoid arthritis associated interstitial lung disease (RA-ILD). The aim of this study is to investigate the risk of mortality in patients with RA-ILD treated with ABA compared to TNFi. This retrospective cohort study utilized TriNetX electronic health record database. We enrolled patients who were diagnosed with RA-ILD and had received a new prescription for either ABA or TNFi. Patients were categorized into two cohorts based on their initial prescription. The primary outcome was all-cause mortality, and secondary outcomes were healthcare utilizations, including hospitalization, critical care services, and mechanical ventilation. Subgroup analyses were performed on age, presence of anti-citrullinated peptide antibodies (ACPA), and cardiovascular risk. Among 34,388 RA-ILD patients, 895 were selected for each group (ABA and TNFi) following propensity score matching. The ABA group exhibited a higher all-cause mortality risk. (HR 1.296, 95% CI 1.006-1.671). Subgroup analysis showed a heightened risk of receiving mechanical ventilation in ABA-treated patients aged 18-64 years old (HR 1.853, 95% CI 1.002-3.426), and those with cardiovascular risk factors (HR 2.015, 95% CI 1.118-3.630). Another subgroup analysis indicated a higher risk of mortality among ABA-treated patients with positive-ACPA. (HR 4.138 95% CI 1.343-12.75). This real-world data research demonstrated a higher risk of all-cause mortality in RA-ILD patients treated with ABA compared to TNFi, particularly those aged 18-64 years, lacking cardiovascular risk factors, and positive-ACPA. ABA was associated with an increased risk of mechanical ventilation in patients aged 18-64 years and those with cardiovascular risk factors., (© 2024. The Author(s).)

The high mortality rate of glioblastoma multiforme (GBM), a lethal primary brain tumor, is attributable to postsurgical recurrence. STAT3, an oncogenic protein, is a signal transducer and transcription activator encourages cancer cell migration and proliferation, which results in resistance to therapy. STAT3 inhibition reduces cancer metastasis and improves patient prognosis. Bt354, a small molecule STAT inhibitor, exhibits significant cytotoxic and anti-proliferative activities against certain cancer types. Here, we demonstrated that exposure of GBM cells (U87 MG) to Bt354 had a significant, concentration-dependent growth suppression. Bt354 also induced apoptosis and downregulated the expression of the epithelial-mesenchymal transition genes. Therefore, this study suggests the potential of Bt354 for treating GBM owing to its ability to induce cytotoxicity., (© 2024 Wiley Periodicals LLC.)

This study examined the concordance between accelerometry-measured and self-reported physical activity (PA) and sedentary time in adults with autism. Twenty-four participants wore an ActiGraph GT3X + accelerometer for seven consecutive days and completed the International Physical Activity Questionnaire-Short Form (IPAQ-SF) on the last day of their study participation. Bland-Altman plots assessed the magnitude of agreement between the two measures. Nearly 80% of the participants accumulated the recommended ≥ 150 min of moderate to vigorous PA (MVPA)/week, but were also sedentary for over nine hours/day according to accelerometry data. Findings showed that adults with autism tended to overreport MVPA (b = 1.606, p < 0.01) and underreport sedentary time (b = 1.161, p = 0.03) via the IPAQ-SF, as compared to objective measurements., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: A stroke frequently results in impaired performance of activities of daily life. Many of these are highly dependent on effective coordination between the two arms. In the context of bimanual movements, cyclic rhythmical bilateral arm coordination patterns can be classified into two fundamental modes: in-phase (bilateral homologous muscles contract simultaneously) and anti-phase (bilateral muscles contract alternately) movements. We aimed to investigate how patients with left (LHS) and right (RHS) hemispheric stroke are differentially affected in both individual-limb control and inter-limb coordination during bilateral movements., Methods: We used kinematic measurements to assess bilateral coordination abilities of 18 chronic hemiparetic stroke patients (9 LHS; 9 RHS) and 18 age- and sex-matched controls. Using KINARM upper-limb exoskeleton system, we examined individual-limb control by quantifying trajectory variability in each hand and inter-limb coordination by computing the phase synchronization between hands during anti- and in-phase movements., Results: RHS patients exhibited greater impairment in individual- and inter-limb control during anti-phase movements, whilst LHS patients showed greater impairment in individual-limb control during in-phase movements alone. However, LHS patients further showed a swap in hand dominance during in-phase movements., Conclusions: The current study used individual-limb and inter-limb kinematic profiles and showed that bilateral movements are differently impaired in patients with left vs. right hemispheric strokes. Our results demonstrate that both fundamental bilateral coordination modes are differently controlled in both hemispheres using a lesion model approach. From a clinical perspective, we suggest that lesion side should be taken into account for more individually targeted bilateral coordination training strategies., Trial Registration: the current experiment is not a health care intervention study., (© 2023. The Author(s).)

Proteolysis-targeting chimera (PROTAC) technology is a disruptive innovation in the drug development community, and over 20 PROTAC molecules are currently under clinical evaluation. These PROTAC molecules contain small-molecule warheads that bind to target proteins. Recently, oligonucleotide-warheaded PROTACs have emerged as a promising new tool to degrade DNA-binding proteins such as transcription factors. In this study, we applied an oligonucleotide-warheaded PROTAC technology to induce the degradation of signal transducer and activator of transcription 3 (STAT3), which is a hard-to-target protein. A double-stranded decoy oligonucleotide specific to STAT3 was conjugated to E3 binders (pomalidomide, VH032, and LCL161) to generate PROTAC molecules that recruited different E3 ubiquitin ligases cereblon (CRBN), von Hippel-Lindau (VHL), and inhibitor of apoptosis protein (IAP), respectively. One of the resulting PROTAC molecules, POM-STAT3, which recruits CRBN, potently induces STAT3 degradation. STAT3 degradation by POM-STAT3 was abolished by scrambling the oligonucleotide sequences of POM-STAT3 and by adding a double-stranded decoy oligonucleotide against STAT3 in a competitive manner, suggesting the significance of oligonucleotide sequences in STAT3 degradation. Moreover, POM-STAT3-induced STAT3 degradation was suppressed by the CRBN binder thalidomide, proteasome inhibitor bortezomib, E1 inhibitor MLN7243, and siRNA-mediated depletion of CRBN, indicating that STAT3 degradation is mediated by the ubiquitin-proteasome system, which involves CRBN as the responsible E3 ubiquitin ligase. Consistent with STAT3 degradation, NCI-H2087 cell viability was severely reduced following POM-STAT3 treatment. Thus, POM-STAT3 is a STAT3 degrader that potentially has cytocidal activity against cancer cells that are highly dependent on STAT3 signaling, which implies that inducing protein degradation by decoy oligonucleotide-warheaded PROTAC molecules could be harnessed to be therapeutic against oncogenic transcription factors., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mikihiko Naito belongs to the Social Cooperation Program of Targeted Protein Degradation supported by Eisai Co., Ltd. and serves as a scientific advisor to UBiENCE Inc. The other authors declare no conflict of interests., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Daily stressors are associated with cognitive decline and increased risk of heart disease, depression, and other debilitating chronic illnesses in midlife adults. Daily stressors tend to occur at home or at work and are more frequent in urban versus rural settings. Conversely, spending time in natural environments such as parks or forests, or even viewing nature-themed images in a lab setting, is associated with lower levels of perceived stress and is hypothesized to be a strong stress "buffer," reducing perceived stress even after leaving the natural setting. However, many studies of daily stress have not captured environmental contexts and relied on end-of-day recall instead of in-the-moment data capture. With new technology, these limitations can be addressed to enhance knowledge of the daily stress experience., Objective: We propose to use our novel custom-built Stress Reports in Variable Environments (STRIVE) ecological momentary assessment mobile phone app to measure the experience of daily stress of midlife adults in free-living conditions. Using our app to capture data in real time will allow us to determine (1) where and when daily stress occurs for midlife adults, (2) whether midlife adults' daily stressors are linked to certain elements of the built and natural environment, and (3) how ecological momentary assessment measurement of daily stress is similar to and different from a modified version of the popular Daily Inventory of Stressful Events measurement tool that captures end-of-day stress reports (used in the Midlife in the United States [MIDUS] survey)., Methods: We will enroll a total of 150 midlife adults living in greater Indianapolis, Indiana, in this study on a rolling basis for 3-week periods. As those in underrepresented minority groups and low-income areas have previously been found to experience greater levels of stress, we will use stratified sampling to ensure that half of our study sample is composed of underrepresented minorities (eg, Black, American Indian, Hispanic, or Native Pacific Islanders) and approximately one-third of our sample falls within low-, middle-, and high-income brackets., Results: This project is funded by the National Institute on Aging from December 2022 to November 2024. Participant enrollment began in August 2023 and is expected to finish in July 2024. Data will be spatiotemporally analyzed to determine where and when stress occurs for midlife adults. Pictures of stressful environments will be qualitatively analyzed to determine the common elements of stressful environments. Data collected by the STRIVE app will be compared with retrospective Daily Inventory of Stressful Events data., Conclusions: Completing this study will expand our understanding of midlife adults' experience of stress in free-living conditions and pave the way for data-driven individual and community-based intervention designs to promote health and well-being in midlife adults., International Registered Report Identifier (irrid): DERR1-10.2196/51845., (©Evan J Jordan, Patrick C Shih, Erik J Nelson, Stephen J Carter, Mario Schootman, Aric A Prather, Xing Yao, Chasie D Peters, Canaan S E Perry. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 05.10.2023.)

Objective: We assessed the feasibility and acceptability of using BACtrack Skyn wearable alcohol monitors for alcohol research in a college student population., Methods: We enrolled n = 5 (Sample 1) and n = 84 (Sample 2) Indiana University undergraduate students to wear BACtrack Skyn devices continuously over a 5-day to 7-day study period. We assessed feasibility in both samples by calculating compliance with study procedures, and by analyzing amount and distributions of device output [e.g., transdermal alcohol content (TAC), temperature, motion]. In Sample 1, we assessed feasibility and acceptability with the Feasibility of Intervention Measure (FIM) scale and the Acceptability of Intervention Measure (AIM) scale., Results: All participants were able to successfully use the alcohol monitors, producing a total of 11,504 h of TAC data. TAC data were produced on 567 days of the 602 total possible days of data collection. The distribution of the TAC data showed between-person variation, as would be expected with between-person differences in drinking patterns. Temperature and motion data were also produced as expected. Sample 1 participants (n = 5) reported high feasibility and acceptability of the wearable alcohol monitors in survey responses with a mean FIM score of 4.3 (of 5.0 possible score) and mean AIM score of 4.3 (of 5.0 possible score)., Conclusions: The high feasibility and acceptability we observed underscore the promise of using BACtrack Skyn wearable alcohol monitors to improve our understanding of alcohol consumption among college students, a population at particularly high risk for alcohol-related harms., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In this paper, we introduce the Analysis Platform for Risk, Resilience, and Expenditure in Disasters (APRED)-a disaster-analytic platform developed for crisis practitioners and economic developers across the United States (US). APRED provides practitioners with a centralized platform for exploring disaster resilience and vulnerability profiles of all counties across the US. The platform comprises five sections including: (1) Disaster Resilience Index, (2) Business Vulnerability Index, (3) Disaster Declaration History, (4) County Profile, and (5) Storm History sections. We further describe our end-to-end human-centered design and engineering process that involved contextual inquiry, community-based participatory design, and rapid prototyping with the support of US Economic Development Administration representatives and regional economic developers across the US. Findings from our study revealed that distributed cognition, content heuristic, shareability, and human-centered systems are crucial considerations for developing data-intensive visualization platforms for resilience planning. We discuss the implications of these findings and inform future research on developing sociotechnical visualization platforms to support resilience planning.

Plasticizers are considered as environmental pollution released from medical devices and increased potential oncogenic risks in clinical therapy. Our previous studies have shown that long-term exposure to di-ethylhexyl phthalate (DEHP)/mono-ethylhexyl phthalate (MEHP) promotes chemotherapeutic drug resistance in colorectal cancer. In this study, we investigated the alteration of glycosylation in colorectal cancer following long-term plasticizers exposure. First, we determined the profiles of cell surface N-glycomes by using mass spectrometry and found out the alterations of α2,8-linkages glycans. Next, we analyzed the correlation between serum DEHP/MEHP levels and ST8SIA6 expression from matched tissues in total 110 colorectal cancer patients. Moreover, clinical specimens and TCGA database were used to analyze the expression of ST8SIA6 in advanced stage of cancer. Finally, we showed that ST8SIA6 regulated stemness in vitro and in vivo. Our results revealed long-term DEHP/MEHP exposure significantly caused cancer patients with poorer survival outcome and attenuated the expression of ST8SIA6 in cancer cells and tissue samples. As expected, silencing of ST8SIA6 promoted cancer stemness and tumorigenicity by upregulating stemness-associated proteins. In addition, the cell viability assay showed enhanced drug resistance in ST8SIA6 silencing cells treated with irinotecan. Besides, ST8SIA6 was downregulated in the advanced stage and positively correlated with tumor recurrence in colorectal cancer. Our results imply that ST8SIA6 potentially plays an important role in oncogenic effects with long-term phthalates exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Adult B-lineage acute lymphoblastic leukemia (B-ALL) with t(4;11)(q21;q23) is very rare. It is characterized by mixed-lineage leukemia and has the potential for lineage switching during the treatment course. We report the disease course of a patient with B-ALL with t(4;11)(q21;q23) to demonstrate that close monitoring of cell morphology and immunophenotyping is necessary to capture the lineage switch at an early stage. Cell morphology, immunophenotyping, and cytogenetics were used to evaluate the patient's disease status. A 36-year-old woman was diagnosed with B-ALL with t(4;11)(q21;q23), which encodes the KMT2A::AFF1 fusion. After the initial induction chemotherapy, her disease remained refractory, and the patient received salvage immunotherapy with blinatumomab and inotuzumab ozogamicin. However, the ALL did not respond. Repeated bone marrow examinations unexpectedly revealed the emergence of a major population of monoblasts, in addition to a minor population of the original B lymphoblasts. The patient was diagnosed with disease evolution from B-ALL to mixed-phenotype acute leukemia (MPAL, B/myeloid). We present this case to highlight the potential of KMT2A-rearranged B-ALL to undergo lineage switch following B-cell targeted therapy. Patients with this kind of B-ALL should therefore be closely monitored to capture potential changes in the nature of the disease and prompt appropriate treatment., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Osteoarthritis is one of the most common diseases and poses a significant medical burden worldwide. Currently, the diagnosis and treatment of osteoarthritis primarily rely on clinical symptoms and changes observed in radiographs or other image modalities. However, identification based on reliable biomarkers would greatly improve early diagnosis, help with precise monitoring of disease progression, and provide aid for accurate treatment. In recent years, several biomarkers for osteoarthritis have been identified, including image modalities and biochemical biomarkers such as collagen degradation products, pro- or anti-inflammatory cytokines, micro RNAs, long non-coding RNAs, and circular RNAs. These biomarkers offer new insights in the pathogenesis of osteoarthritis and provide potential targets for further research. This article reviews the evolution of osteoarthritis biomarkers from the perspective of pathogenesis and emphasizes the importance of continued research to improve the diagnosis, treatment, and management of osteoarthritis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Epilepsy is a common chronic neurological disease. People with epilepsy (PWE) and their caregivers face several challenges related to their epilepsy management, including quality of care, care coordination, side effects, and stigma management. The sociotechnical issues of the information management contexts and challenges for epilepsy care may be mitigated through effective information management. We conducted 4 focus groups with 5 PWE and 7 caregivers to explore how they manage epilepsy-related information and the challenges they encountered. Primary issues include challenges of finding the right information, complexities of tracking and monitoring data, and limited information sharing. We provide a framework that encompasses three attributes - individual epilepsy symptoms and health conditions, information complexity, and circumstantial constraints. We suggest future design implications to mitigate these challenges and improve epilepsy information management and care coordination.

Glioblastoma multiforme (GBM) is a common central nervous system disease with a poor prognosis; its five-year survival rate is <5 %, and its median survival of 15 months. Current treatment includes chemotherapy with temozolomide, which is ineffective against GBM, suggesting an urgent need to develop novel therapies. This study evaluated isoaaptamine and aaptamine in the GBM cell lines for cell viability; GBM 8401, U87 MG, U138 MG, and T98G. Our findings showed that isoaaptamine was more potent than its iso-form aaptamine in these four cell lines, and GBM 8401 was most sensitive to isoaaptamine. The study in GBM 8401 cells showed that apoptosis was induced by isoaaptamine with increased cleaved caspase 3 and poly ADP-ribose polymerase (PARP). Moreover, isoaaptamine enhanced oxidative stress by increasing the levels of reactive oxygen species (ROS), inhibiting mitochondrial and cellular superoxidase dismutases (SOD1&2), peroxidase and an anti-apoptotic protein (Bcl-2), and disrupting mitochondrial membrane potential. In addition, the oxygen consumption rates and activities of mitochondrial complexes I-V were significantly reduced. Mitochondrial dynamics were prone to fission instead of fusion after isoaaptamine treatment, and ATP synthesis was ablated. Also, autophagy-related acidic organelle vesicles were formed, indicating autophagy was triggered. Overall, isoaaptamine-induced ROS overproduction in mitochondria could cause mitochondrial dysfunction, apoptosis, and autophagy in the GBM cells., Competing Interests: Conflict of Interest Statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine. Published by Elsevier Masson SAS.. All rights reserved.)

The pulmonary artery catheter (PAC)-despite its invasiveness-remains the gold standard for cardiac output (CO) monitoring. The FloTrac system, a less invasive hemodynamic monitor has been developed, which estimates CO using arterial pressure waveform analysis without external calibration. Recently, an upgraded version of FloTrac system with improved algorithm to follow changes in vascular resistance was introduced into the market. The aim of this study was to assess the reliability of the CO estimated from the fourth-generation FloTrac/EV1000 system (CO FT ) compared to that measured with PAC using the thermodilution method (CO PAC ) during robotic-assisted off-pump coronary artery bypass (OPCAB) surgery. CO FT and CO PAC were obtained simultaneously at 4 predefined time points during robotic-assisted OPCAB: 5 min after the induction of general anesthesia (T1), after starting one-lung ventilation (T2), after capnothorax (T3), and after mini-thoracotomy was performed (T4). The agreement of data was investigated by Bland-Altman analysis. Thirty-four patients were initially enrolled. After exclusion, 32 patients and a total of 128 paired CO measurements were obtained. The overall bias was 1.46 L/min, the 95% limits of agreements were - 3.40 to 6.33 L/min, and the percentage error was 72.98%. Regression analysis of the systemic vascular resistance index (SVRI) and the bias between CO PAC and CO FT showed that the bias was moderately correlated with the SVRI (r 2  = 0.43; p < 0.0001). Despite a software upgrade, the reliability of the fourth-generation FloTrac/EV1000™ system during robotic-assisted OPCAB to estimate CO was not acceptable, especially in patients with low SVRI., (© 2022. Springer Japan KK, part of Springer Nature.)

Transcription factors (TFs) and RNA-binding proteins (RBPs) have long been considered undruggable, mainly because they lack ligand-binding sites and are equipped with flat and narrow protein surfaces. Protein-specific oligonucleotides have been harnessed to target these proteins with some satisfactory preclinical results. The emerging proteolysis-targeting chimera (PROTAC) technology is no exception, utilizing protein-specific oligonucleotides as warheads to target TFs and RBPs. In addition, proteolysis by proteases is another type of protein degradation. In this review article, we discuss the current status of oligonucleotide-based protein degraders that are dependent either on the ubiquitin-proteasome system or a protease, providing a reference for the future development of degraders.

Background: Post-caesarean section analgesia is important physiologically and psychologically for both mothers and infants. Patient-controlled analgesia is a well-established method of administering opioids for postoperative pain. However, to date, no study has systematically investigated the effects of opioids administered through intravenous patient-controlled analgesia (IVPCA) or patient-controlled epidural analgesia (PCEA) in parturients who have undergone caesarean section., Methods: This systematic review and network meta-analysis aimed to evaluate the analgesic and adverse effects of opioids administered via IVPCA or PCEA in parturients who have undergone a caesarean section. PubMed, Embase, Scopus, Web of Science, and Cochrane Library were searched from inception through 02 10, 2022 for relevant records. Randomised controlled trials (RCTs) that compared opioids administered via IVPCA or PCEA and reported outcomes of interest were included. Studies were excluded if the solution for patient-controlled analgesia contained antiemetics and/or other analgesics in addition to opioids. The methodological quality of RCTs was assessed using the revised Cochrane Risk of Bias Tool. Summary data were extracted from each eligible study. The primary outcome was pain intensity, and the secondary outcomes were opioid-related adverse effects. Frequentist network meta-analyses were performed using a contrast-based random-effects model. This study is registered with PROSPERO, CRD42021254040., Findings: Twenty-three studies with 2589 parturients were included. Compared with IVPCA morphine as a reference treatment, PCEA fentanyl had better analgesic effects at 4 h (mean difference [MD] in the visual analogue scale score, -0.75; 95% confidence interval [CI] [-1.16, -0.34]) and 8 h (MD, -0.93; 95% CI [-1.57, -0.28]) and yielded lower odds of developing nausea/vomiting (odds ratio [OR], 0.27; 95% CI [0.09, 0.80]) and sedation/drowsiness (OR, 0.22; 95% CI [0.11, 0.45]). However, PCEA fentanyl may be more likely to cause pruritus than IVPCA treatments., Interpretation: Considering the analgesic efficacy; opioid-induced nausea, vomiting, and sedation; and the well-being of breastfed infants, PCEA fentanyl may be the treatment of choice for post-caesarean section analgesia., Funding: The Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation (TCRD-TPE-111-27)., Competing Interests: All authors declare no competing interests., (© 2022 The Author(s).)

Long noncoding (lnc)RNAs are reported to be key regulators of tumor progression, including hepatocellular carcinoma (HCC). The lncRNA long intergenic noncoding RNA 00673 (LINC00673) was indicated to play an important role in HCC progression, but the impacts of genetic variants (single-nucleotide polymorphisms, SNPs) of LINC00673 on HCC remain unclear. A TaqMan allelic discrimination assay was performed to analyze the genotypes of three tagging SNPs, viz., rs9914618 G > A, rs6501551 A > G, and rs11655237 C > T, of LINC00673 in 783 HCC patients and 1197 healthy subjects. Associations of functional SNPs of LINC00673 with HCC susceptibility and clinicopathologic variables were analyzed by logistic regression models. After stratification by confounding factor, we observed that elderly patients (≥60 years) with the LINC00673 rs9914618 A allele had an increased risk of developing HCC under a codominant model (p = 0.025) and dominant model (p = 0.047). Moreover, elderly patients carrying the GA + AA genotype of rs9914618 exhibited a higher risk of having lymph node metastasis compared to those who were homozygous for the major allele (p = 0.013). Genotype screening of rs9914618 in HCC cell lines showed that cells carrying the AA genotype expressed higher LINC00673 levels compared to the cells carrying the GG genotype. Further analyses of clinical datasets from the Cancer Genome Atlas (TCGA) showed that LINC00673 expressions were upregulated in HCC tissues compared to normal tissues, and were correlated with advanced clinical stages and poorer prognoses. In conclusions, our results suggested that the LINC00673 rs9914618 polymorphism may be a promising HCC biomarker, especially in elderly populations.

Intraocular pressure (IOP) is crucial to the well-being of eyes. During anesthesia, the administration of succinylcholine and endotracheal intubation are associated with an increase in IOP, which may be attenuated by short-acting opioids. However, the drug of choice among the commonly used short-acting opioids is unclear. This study aimed to evaluate the effects of fentanyl, sufentanil, alfentanil, and remifentanil on IOP measured after the administration of succinylcholine and after endotracheal intubation in patients undergoing general anesthesia. Five databases were searched. Randomized controlled trials (RCTs) that compared short-acting opioids and reported at least one of the clinical outcomes of interest were included. Nine RCTs with 357 patients were included. Remifentanil (1 μg kg -1 ) more effectively alleviated the increase in IOP than the placebo after the administration of succinylcholine [mean difference (MD) of IOP, -3.64; confidence interval (CI), -5.47 to -1.81 and after endotracheal intubation (MD, -9.71; CI, -11.91 to -7.51). Remifentanil (1 μg kg -1 ) ranked the best in terms of both attenuating the increase in IOP after the administration of succinylcholine [surface under the cumulative ranking curve (SUCRA), 0.91; normalized entropy (NE), 0.47; and after endotracheal intubation (SUCRA, 0.89; NE, 0.54) among all of the treatments. Remifentanil (1 μg kg -1 ) should be considered the drug of choice in the circumstances where increased IOP is a great concern.

Oral squamous cell carcinoma (OSCC) affects tens of thousands of people worldwide. Despite advances in cancer treatment, the 5-year survival rate of patients with late-stage OSCC is low at 50-60%. Therefore, the development of anti-OSCC therapy is necessary. We evaluated the effects of marine-derived triterpene stellettin B in human OC2 and SCC4 cells. Stellettin B dose-dependently decreased the viability of both cell lines, with a significant reduction in OC2 cells at ≥0.1 µM at 24 and 48 h, and in SCC4 cells at ≥1 µM at 24 and 48 h. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells were significantly observed at 20 µM of stellettin B at 48 h, with the overexpression of cleaved caspase3 and cleaved poly(ADP-ribose) polymerase (PARP). Moreover, mitochondrial respiratory functions were ablated by stellettin B. Autophagy-related LC3-II/LC3-I ratio and Beclin-1 proteins were increased, whereas p62 was decreased. At 20 µM at 48 h, the expression levels of the endoplasmic reticulum (ER) stress biomarkers calnexin and BiP/GRP78 were significantly increased and mitogen-activated protein kinase (MAPK) signaling pathways were activated. Further investigation using the autophagy inhibitor 3-methyladenine (3-MA) demonstrated that it alleviated stellettin B-induced cell death and autophagy. Overall, our findings show that stellettin B induces the ER stress, mitochondrial stress, apoptosis, and autophagy, causing cell death of OSCC cells.

Background: Physical activity (PA) has an impact on physical and mental health in neurotypical populations, and addressing these variables may improve the prevalent burden of anxiety in adults with autism spectrum disorder (ASD). Gamified mobile apps using behavior change techniques present a promising way of increasing PA and reducing sedentary time, thus reducing anxiety in adults with ASD., Objective: This study aimed to compare the effectiveness of a gamified and behavior change technique-based mobile app, PuzzleWalk, versus a commercially available app, Google Fit, on increasing PA and reducing sedentary time as an adjunct anxiety treatment for this population., Methods: A total of 24 adults with ASD were assigned to either the PuzzleWalk or Google Fit group for 5 weeks using a covariate-adaptive randomization design. PA and anxiety were assessed over 7 days at 3 different data collection periods (ie, baseline, intervention start, and intervention end) using triaxial accelerometers and the Beck Anxiety Inventory. Group differences in outcome variables were assessed using repeated-measures analysis of covariance, adjusting for age, sex, and BMI., Results: The findings indicated that the PuzzleWalk group spent a significantly longer amount of time on app use compared with the Google Fit group (F 2,38 =5.07; P=.01; partial η 2 =0.21), whereas anxiety was unfavorably associated with increases in light PA and decreases in sedentary time after intervention (all P<.05)., Conclusions: Further research is needed to clarify the determinants of physical and mental health and their interrelationship in adults with ASD to identify the factors that facilitate the use and adoption of mobile health technologies in these individuals. Despite these mixed results, the small changes in PA or anxiety may be clinically significant for adults with ASD., Trial Registration: ClinicalTrials.gov NCT05466617; https://clinicaltrials.gov/show/NCT05466617., (©Daehyoung Lee, Georgia C Frey, Donetta J Cothran, Jaroslaw Harezlak, Patrick C Shih. Originally published in JMIR Formative Research (https://formative.jmir.org), 28.07.2022.)

Glioblastoma multiforme (GBM) is a cancer of largely unknown cause that leads to a 5-year survival rate of approximately 7% in the United States. Current treatment strategies are not effective, indicating a strong need for the development of novel therapies. In this study, the outcomes of sinularin, a marine-derived product, were evaluated against GBM. Our cellular studies using GBM cells revealed that sinularin induces cell death. The measured half maximal inhibitory concentrations (IC 50 ) values ranged from 30 to 6 μM at 24-72 h. Cell death was induced via the generation of ROS leading to mitochondria-mediated apoptosis. This was evidenced by annexin V/propidium iodine staining and an upregulation of cleaved forms of the pro-apoptotic proteins caspase 9, 3, and PARP, and supported by CellROX TM Green, MitoSOX TM Red, and CM-H 2 DCFDA staining methods. In addition, we observed a downregulation of the antioxidant enzymes SOD1/2 and thioredoxin. Upon treatment with sinularin at the ~IC 50 concentration, mitochondrial respiration capacities were significantly reduced, as shown by measuring the oxygen consumption rates and enzymatic complexes of oxidative phosphorylation. Intriguingly, sinularin significantly inhibited indicators of angiogenesis such as vessel tube formation, cell migration, and cell mobility in human umbilical vein endothelial cells or the fusion cell line EA.Hy926. Lastly, in a transgenic zebrafish model, intersegmental vessel formation was also significantly inhibited by sinularin treatment. These findings indicate that sinularin exerts anti-brain cancer properties that include apoptosis induction but also antiangiogenesis., Competing Interests: The authors declare no conflict of interest.

Environmental enrichment is adding complexity to an environment that has a positive impact on a captive animal as a necessity of care. Computing technology is being rapidly weaved throughout the space in both enrichment devices as well as evaluating enrichment outcomes. In this article, we present a scoping review of 102 captive animal enrichment studies and propose a contextual lens for exploring current practices. We discuss the importance of directed growth in species inclusion, transitioning beyond anthro-centric designs, and utilizing shared methodologies.

The efficacy of radiotherapy has long known to be limited by the emergence of resistance. The four Rs of radiotherapy (DNA damage repair, reoxygenation, redistribution of the cell cycle, and repopulation) are generally accepted concepts in radiobioolgy. Recent studies have strongly linked signal transducer and activator of transcription 3 (STAT3) to the regulation of cancer stemness and radioresistance. In particular, a STAT3 pathway inhibitor napabucasin, claimed to be the first cancer stemness antagonist in clinical trials, strengthens the link. However, no reviews connect STAT3 with the four Rs of radiotherapy. Herein, the evidence-based role of STAT3 in radioresistance is discussed in relation to the four Rs of radiotherapy. The proposed mechanisms include upstream and downstream effector proteins of STAT3, including FOXM1, MELK, NEK2, AKT, EZH2, and HIF1α. Downstream transcriptional products of the mechanistically-related proteins are involved in cancer stemness, anti-apoptosis, and the four Rs of radiotherapy. Utilizing selective inhibitors of the mechanistically-related proteins has shown promising antagonism of radioresistance, suggesting that the expression levels of these proteins may be biomarkers for the prediction of radiotherapeutic outcomes, and that this molecular mechanism may provide a rational axis through which to treat radioresistance., Competing Interests: Declaration of Competing Interest The author declares that there are no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)