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IntroductionThe Meta VCI Map consortium performs meta-analyses on strategic lesion locations for vascular cognitive impairment using lesion-symptom mapping. Integration of data from different cohorts will increase sample sizes, to improve brain lesion coverage and support comprehensive lesion-symptom mapping studies.MethodsCohorts with available imaging on white matter hyperintensities or infarcts and cognitive testing were invited. We performed a pilot study to test the feasibility of multicenter data processing and analysis and determine the benefits to lesion coverage.ResultsForty-seven groups have joined Meta VCI Map (stroke n = 7800 patients; memory clinic n = 4900; population-based n = 14,400). The pilot study (six ischemic stroke cohorts, n = 878) demonstrated feasibility of multicenter data integration (computed tomography/magnetic resonance imaging) and achieved marked improvement of lesion coverage.DiscussionMeta VCI Map will provide new insights into the relevance of vascular lesion location for cognitive dysfunction. After the successful pilot study, further projects are being prepared. Other investigators are welcome to join.

Understanding how sleep affects the glymphatic system and human brain networks is crucial for elucidating the neurophysiological mechanism underpinning aging-related memory declines. We analyzed a multimodal dataset collected through magnetic resonance imaging (MRI) and polysomnographic recording from 72 older adults. A proxy of the glymphatic functioning was obtained from the Diffusion Tensor Image Analysis along the Perivascular Space (DTI-ALPS) index. Structural and functional brain networks were constructed based on MRI data, and coupling between the two networks (SC-FC coupling) was also calculated. Correlation analyses revealed that DTI-ALPS was negatively correlated with sleep quality measures [e.g., Pittsburgh Sleep Quality Index (PSQI) and apnea-hypopnea index]. Regarding human brain networks, DTI-ALPS was associated with the strength of both functional connectivity (FC) and structural connectivity (SC) involving regions such as the middle temporal gyrus and parahippocampal gyrus, as well as with the SC-FC coupling of rich-club connections. Furthermore, we found that DTI-ALPS positively mediated the association between sleep quality and rich-club SC-FC coupling. The rich-club SC-FC coupling further mediated the association between DTI-ALPS and memory function in good sleepers but not in poor sleepers. The results suggest a disrupted glymphatic-brain relationship in poor sleepers, which underlies memory decline. Our findings add important evidence that sleep quality affects cognitive health through the underlying neural relationships and the interplay between the glymphatic system and multimodal brain networks., (© 2024. The Author(s).)

This study aims to explore the origin effects of imported fruits, with a particular focus on environmental sustainability. Data were collected in 2021 through in-person surveys administered to primary food shoppers in Taipei. Total valid samples were 199. SAS software was used in analytics in this study. Multivariate analysis was employed to analyze the influences of various origin effects-advertising, environment, technology, pollution, image, and economy-on purchasing decisions. Major findings indicate that production technology has the most substantial positive influence on purchasing decisions, followed by country image and environmental aspects. Kernel density estimation further revealed that perceptions of environmental sustainability are multifaceted, with pollution being a more consistently understood factor compared to the broader environmental impacts. These findings underscore the importance of tailoring marketing strategies and policies to align with consumer perceptions regarding environmental sustainability, fostering trust, and promoting sustainable practices within the fruit import industry. The study provides valuable insights but is limited by its geographic focus on Taipei, the cross-sectional nature of the data, and the specific origin effects examined. Future research should consider broader geographic areas and additional product categories to enhance generalizability., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

The association of anosmia/ageusia with a positive severe respiratory syndrome coronavirus 2 (SARS-CoV-2) test is well-established, suggesting these symptoms are reliable indicators of coronavirus disease 2019 (COVID-19) infection. This study investigates the clinical characteristics and systemic inflammatory markers in hospitalized COVID-19 patients in Taiwan, focusing on those with anosmia/ageusia. We conducted a retrospective observational study on 231 hospitalized COVID-19 patients (alpha variant) from April to July 2021. Clinical symptoms, dyspnea grading, and laboratory investigations, including neutrophil-lymphocyte ratios (NLRs), platelet-lymphocyte ratios (PLRs), and ANDC scores (an early warning score), were analyzed. Cough (64.1%), fever (58.9%), and dyspnea (56.3%) were the most common symptoms, while anosmia/ageusia affected 9% of patients. Those with anosmia/ageusia were younger, had lower BMI, lower systemic inflammatory markers, and better ANDC scores than those without these symptoms. Female patients exhibited lower NLR values and ANDC scores compared to male patients (all p < 0.05). Multivariable regression analysis demonstrated significant associations between NLR and CRP and ferritin levels (all p < 0.01), and between PLR and ESR and ferritin levels (p < 0.01). Categorized ANDC scores significantly correlated with the total hospital length of stay (all p < 0.05). Despite ethnic differences in the prevalence of anosmia/ageusia, our study highlights similar clinical presentations and inflammatory profiles to those observed in Western countries. The ANDC score effectively predicted hospital stay duration. These findings suggest that anosmia/ageusia may be associated with less severe disease and a lower inflammatory response, particularly in younger and female patients. The ANDC score can serve as a valuable prognostic tool in assessing the severity and expected hospital stay of COVID-19 patients., (© 2024. The Author(s).)

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease leading to end-stage renal disease. Total kidney volume (TKV) measurement has been considered as a surrogate in the evaluation of disease severity and prognostic predictor of ADPKD. However, the traditional manual measurement of TKV by medical professionals is labor-intensive, time-consuming, and human error prone., Materials and Methods: In this investigation, we conducted TKV measurements utilizing magnetic resonance imaging (MRI) data. The dataset consisted of 30 patients with ADPKD and 10 healthy individuals. To calculate TKV, we trained models using both coronal- and axial-section MRI images. The process involved extracting images in Digital Imaging and Communications in Medicine (DICOM) format, followed by augmentation and labeling. We employed a U-net model for image segmentation, generating mask images of the target areas. Subsequent post-processing steps and TKV estimation were performed based on the outputs obtained from these mask images., Results: The average TKV, as assessed by medical professionals from the testing dataset, was 1501.84 ± 965.85 mL with axial-section images and 1740.31 ± 1172.21 mL with coronal-section images, respectively ( p = 0.73). Utilizing the deep learning model, the mean TKV derived from axial- and coronal-section images was 1536.33 ± 958.68 mL and 1636.25 ± 964.67 mL, respectively ( p = 0.85). The discrepancy in mean TKV between medical professionals and the deep learning model was 44.23 ± 58.69 mL with axial-section images ( p = 0.8) and 329.12 ± 352.56 mL with coronal-section images ( p = 0.9), respectively. The average variability in TKV measurement was 21.6% with the coronal-section model and 3.95% with the axial-section model. The axial-section model demonstrated a mean Dice Similarity Coefficient (DSC) of 0.89 ± 0.27 and an average patient-wise Jaccard coefficient of 0.86 ± 0.27, while the mean DSC and Jaccard coefficient of the coronal-section model were 0.82 ± 0.29 and 0.77 ± 0.31, respectively., Conclusion: The integration of deep learning into image processing and interpretation is becoming increasingly prevalent in clinical practice. In our pilot study, we conducted a comparative analysis of the performance of a deep learning model alongside corresponding axial- and coronal-section models, a comparison that has been less explored in prior research. Our findings suggest that our deep learning model for TKV measurement performs comparably to medical professionals. However, we observed that varying image orientations could introduce measurement bias. Specifically, our AI model exhibited superior performance with axial-section images compared to coronal-section images.

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity disease caused by Aspergillus fumigatus ( Af ), prevalent in persons with cystic fibrosis (CF) or asthma. In ABPA, Af proteases drive a T-helper cell-2 (Th2)-mediated allergic immune response leading to inflammation that contributes to permanent lung damage. Corticosteroids and antifungals are the mainstays of therapies for ABPA. However, their long-term use has negative sequelae. The treatment of patients with CF (pwCF) has been revolutionized by the efficacy of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy. Pharmacological improvement in CFTR function with highly effective elexacaftor/tezacaftor/ivacaftor (ETI) provides unprecedented improvements in lung function and other clinical outcomes of pwCF. The mechanism behind the improvement in patient outcomes is a continued topic of investigation as our understanding of the role of CFTR function evolves. As ETI therapy gains traction in CF management, understanding its potential impact on ABPA, especially on the allergic immune response pathways and Af infection becomes increasingly crucial for optimizing patient outcomes. This literature review aims to examine the extent of these findings and expand our understanding of the already published research focusing on the intersection between ABPA therapeutic approaches in CF and the rapid impact of the evolving CFTR modulator landscape. While our literature search yielded limited reports specifically focusing on the role of CFTR modulator therapy on CF-ABPA, findings from epidemiologic and retrospective studies suggest the potential for CFTR modulator therapies to positively influence pulmonary outcomes by addressing the underlying pathophysiology of CF-ABPA, especially by decreasing inflammatory response and Af colonization. Thus, this review highlights the promising scope of CFTR modulator therapy in decreasing the overall prevalence and incidence of CF-ABPA.

Abstract: Organizing pneumonia (OP) is a known noninfectious pulmonary complication following allogeneic hematopoietic cell transplant (HCT) and represents a significant risk factor for nonrelapse mortality in HCT recipients. Unlike bronchiolitis obliterans syndrome, it is not universally acknowledged as a distinctive pulmonary manifestation of chronic graft-versus-host disease (cGVHD) and, therefore, its diagnostic criteria and management approach are lacking. Given its shared similar clinical features and radiological and histologic findings to OP in the non-HCT population, the diagnostic approach and treatment strategy for OP in HCT recipients is largely adapted from the non-HCT population. In this article, we aim to enhance the understanding of OP within the context of cGVHD following HCT and distinguish its clinical features and treatment strategy from non-HCT counterparts, thereby reinforcing its recognition as a pulmonary manifestation of graft-versus-host disease. We will propose the diagnostic criteria and outline our approach in diagnosis and treatment strategy, highlighting the potential challenges that may arise in each process. Finally, we will discuss knowledge gaps in this field and identify the area of need for future research., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Amyloid plaques, implicated in Alzheimer's disease, exhibit a spatial propagation pattern through interconnected brain regions, suggesting network-driven dissemination. This study utilizes PET imaging to investigate these brain connections and introduces an innovative method for analyzing the amyloid network. A modified version of a previously established method is applied to explore distinctive patterns of connectivity alterations across cognitive performance domains. PET images illustrate differences in amyloid accumulation, complemented by quantitative network indices. The normal control group shows minimal amyloid accumulation and preserved network connectivity. The MCI group displays intermediate amyloid deposits and partial similarity to normal controls and AD patients, reflecting the evolving nature of cognitive decline. Alzheimer's disease patients exhibit high amyloid levels and pronounced disruptions in network connectivity, which are reflected in low levels of global efficiency (Eg) and local efficiency (Eloc). It is mostly in the temporal lobe where connectivity alterations are found, particularly in regions related to memory and cognition. Network connectivity alterations, combined with amyloid PET imaging, show potential as discriminative markers for different cognitive states. Dataset-specific variations must be considered when interpreting connectivity patterns. The variability in MCI and AD overlap emphasizes the heterogeneity in cognitive decline progression, suggesting personalized approaches for neurodegenerative disorders. This study contributes to understanding the evolving network characteristics associated with normal cognition, MCI, and AD, offering valuable insights for developing diagnostic and prognostic markers., (© 2024. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

The treatment of non-small cell lung cancer (NSCLC) is known as a significant level of unmet medical need in spite of the progress in targeted therapy and personalized therapy. Overexpression of the Na + /K + -ATPase contributes to NSCLC progression, suggesting its potentiality in antineoplastic approaches. Epi-reevesioside F, purified from Reevesia formosana, showed potent anti-NSCLC activity through inhibiting the Na + /K + -ATPase, leading to internalization of α1- and α3-subunits in Na + /K + -ATPase and suppression of Akt-independent mTOR-p70S6K-4EBP1 axis. Epi-reevesioside F caused a synergistic amplification of apoptosis induced by gefitinib but not cisplatin, docetaxel, etoposide, paclitaxel, or vinorelbine in both NCI-H460 and A549 cells. The synergism was validated by enhanced activation of the caspase cascade. Bax cleavage, tBid formation, and downregulation of Bcl-xL and Bcl-2 contributed to the synergistic apoptosis induced by the combination treatment of epi-reevesioside F and gefitinib. The increase of membrane DR4 and DR5 levels, intracellular Ca 2+ concentrations, and active m-calpain expression were responsible for the caspase-8 activation and Bax cleavage. The increased α-tubulin acetylation and activation of MAPK (i.e., p38 MAPK, Erk, and JNK) depending on cell types contributed to the synergistic mechanism under combination treatment. These signaling pathways that converged on profound c-Myc downregulation led to synergistic apoptosis in NSCLC. In conclusion, the data suggest that epi-reevesioside F inhibits the Na + /K + -ATPase and displays potent anti-NSCLC activity. Epi-reevesioside F sensitizes gefitinib-induced apoptosis through multiple pathways that converge on c-Myc downregulation. The data support the inhibition of Na + /K + -ATPase as a switch-on mechanism to sensitize gefitinib-induced anti-NSCLC activity., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The syllabus is a required document for all courses to provide students with course information, policies, and assignment deadlines. The goals of this study were to investigate students' perception of the role of the syllabus, preferred location of assignment deadlines, and preferred style of receiving deadline notifications. Faculty ( n = 14) and students ( n = 324) from community colleges through professional schools were invited to participate and complete a survey. We used a mixed-method design of survey questions, and the results demonstrated that students defined a syllabus as both a contract and a learning tool and that it should be flexible. Students ranked assignment deadlines as the most important part of the syllabus, yet a follow-up question indicated that most referred to four distinct locations in their learning management system (LMS) to find these deadlines. Although students preferred to receive deadline notifications on their smartphones, they also wanted to be reminded by faculty in class. This study helps faculty to obtain a glimpse of current student practices. We recommend that faculty communicate with students the role and expected use of the syllabus in their course while emphasizing its use to identify deadlines. This renewed practice will be time well spent to avoid student confusion and missed deadlines. NEW & NOTEWORTHY With the adoption of learning management systems (LMSs), students may no longer rely on the syllabus to locate or confirm assignment deadlines and instead rely on various LMS locations, which may not be accurate. We suggest that faculty consider taking the time to review the role and use of the syllabus on the first day of class to ensure that students know where to access current assignment deadlines to avoid confusion and missed deadlines.

Objective: To evaluate the impact of inflammation on anticoagulation monitoring for patients supported with extracorporeal membrane oxygenation (ECMO)., Design: Prospective single-center cohort study., Setting: University-affiliated tertiary care academic medical center., Participants: Adult venovenous and venoarterial ECMO patients anticoagulated with heparin/ MEASUREMENTS AND MAIN RESULTS: C-Reactive protein (CRP) was used as a surrogate for overall inflammation. The relationship between CRP and the partial thromboplastin time (PTT, seconds) was evaluated using a CRP-insensitive PTT assay (PTT-CRP) in addition to measurement using a routine PTT assay. Data from 30 patients anticoagulated with heparin over 371 ECMO days was included. CRP levels (mg/dL) were significantly elevated (median, 17.2; interquartile range [IQR], 9.2-26.1) and 93% of patients had a CRP of ≥5. The median PTT (median 58.9; IQR, 46.9-73.3) was prolonged by 11.3 seconds compared with simultaneously measured PTT-CRP (median, 47.6; IQR, 40.1-55.5; p < 0.001). The difference between PTT and PTT-CRP generally increased with CRP elevation from 2.7 for a CRP of <5.0 to 13.0 for a CRP between 5 and 10, 17.7 for a CRP between 10 and 15, and 15.1 for a CRP of >15 (p < 0.001). In a subgroup of patients, heparin was transitioned to argatroban, and a similar effect was observed (median PTT, 62.1 seconds [IQR, 53.0-78.5 seconds] vs median PTT-CRP, 47.6 seconds [IQR, 41.3-57.7 seconds]; p < 0.001)., Conclusions: Elevations in CRP are common during ECMO and can falsely prolong PTT measured by commonly used assays. The discrepancy due to CRP-interference is important clinically given narrow PTT targets and may contribute to hematological complications., 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 © 2024 Elsevier Inc. All rights reserved.)

Background: Family caregivers of persons with dementia are faced with complex caregiving management needs. This study had two aims: (1) to identify caregiving management needs of family caregivers of persons with dementia and (2) identify any variables that might influence these needs., Methods: This cross-sectional study recruited family caregivers of persons with dementia (N = 250) through referrals from clinicians at a dementia outpatient clinic in Northern Taiwan. Data were collected with a 32-item researcher-developed instrument, the Caregiving Management Needs Scale (CMNS), to identify management needs specific to family caregivers of persons with dementia. The CMNS was comprised of questions about the types of assistance or support family caregivers would like to receive to facilitate caregiving., Results: CMNS scores indicated caregivers had moderate management needs. Caregivers of relatives with a moderate severity of dementia had significantly higher scores on the CMNS compared with caregivers of persons with very mild dementia (p < 0.01). Linear regression analysis indicated significant predictors of high caregiving management needs were caregivers who were female (p < 0.01), and persons with dementia with behavioral problems (p < 0.01), low scores for Activities of Daily Living (p < 0.01), regular medication adherence (p < 0.01), and use of long-term care services (p < 0.001) were significant (F[13, 236] = 7.12; p < 0.001; R 2  = 28.2%)., Conclusions: Understanding variables and predictors of caregiving management needs for family caregivers could reduce the complexity of caregiving., Trial Registration: ClinicalTrials.gov NCT05151185., (© 2024. The Author(s).)

Extracellular vesicles (EVs) are present in blood at much lower concentrations (5-6 orders of magnitude) compared to lipoprotein particles (LP). Because LP and EV overlap in size and density, isolating high-purity EVs is a significant challenge. While the current two-step sequential EV isolation process using size-expression chromatography (SEC) followed by a density gradient (DG) achieves high purity, the time-consuming ultracentrifugation (UC) step in DG hinders workflow efficiency. This paper introduces an optimized magnetic bead reagent, LipoMin, functionalized with glycosaminoglycans (GAGs), as a rapid alternative for LP removal during the second-step process in about 10 minutes. We evaluated LipoMin's efficacy on two sample types: (a) EV fractions isolated by size exclusion chromatography (SEC + LipoMin) and (b) the pellet obtained from ultracentrifugation (UC + LipoMin). The workflow is remarkably simple, involving a 10 min incubation with LipoMin followed by magnetic separation of the LP-depleted EV-containing supernatant. Results from enzyme-linked immunosorbent assay (ELISA) revealed that LipoMin removes 98.2% ApoB from SEC EV fractions, comparable to the LP removal ability of DG in the SEC + DG two-step process. Importantly, the EV yield (CD81 ELISA) remained at 93.0% and Western blot analysis confirmed that key EV markers, flotillin and CD81, were not compromised. Recombinant EV (rEV), an EV reference standard, was spiked into SEC EV fractions and recovered 89% of CD81 protein. For UC + LipoMin, ApoA1 decreased by 76.5% while retaining 90.7% of CD81. Notably, both colorectal cancer (CRC) and Alzheimer's disease (AD) samples processed by SEC + LipoMin and UC + LipoMin displayed clear expression of relevant EV and clinical markers. With a 10 min workflow (resulting in a 96% time saving compared to the traditional method), the LipoMin reagent offers a rapid and efficient alternative to DG for LP depletion, paving the way for a streamlined SEC + LipoMin two-step EV isolation process.

Effective spatial visualization and reasoning skills are often credited for students' success in science and engineering courses. However, students enrolled in these science courses are not always exposed to or trained properly on the best ways to utilize models to aid in their learning. Improving spatial visualization techniques with 3D models, such as molecular and DNA modeling kits, is often suggested to facilitate students' ability to conceptualize compounds in two and three dimensions. Here, we investigate what techniques students use to conceptualize 2D representations of various biomolecules with the use of 3D models by interviewing undergraduate students from various natural science and engineering disciplines in task-based, think-aloud sessions. After scoring and analyzing the participant data we explored some of the techniques used among successful scoring participants, including the use of informal models to transition between 2D and 3D. Additional techniques used by students who were able to successfully conceptualize 3D images included starting with smaller, granular details to inductively make conclusions when thinking between two and three dimensions. We find that (1) students who anchor their thinking in 3D models show a deeper level of understanding in initially solving science problems successfully, and (2) proper 3D model use and spatial visualization techniques may improve students' abilities to accurately visualize 2D and 3D representations of molecules in science courses. Our results demonstrate that implementing spatial visualization training to teach students how to effectively use 3D models may improve students' problem-solving techniques in science curricula., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society and Division of Chemical Education, Inc.)

Mycoviruses are viruses that infect fungi and are widespread across all major fungal taxa, exhibiting great biological diversity. Since their discovery in the 1960s, researchers have observed a myriad of fungal phenotypes altered due to mycoviral infection. In this review, we examine the nuanced world of mycoviruses in the context of the medically and agriculturally important fungal genus, Aspergillus . The advent of RNA sequencing has revealed a previous underestimate of viral prevalence in fungi, in particular linear single-stranded RNA viruses, and here we outline the diverse viral families known to date that contain mycoviruses infecting Aspergillus . Furthermore, we describe these novel mycoviruses, highlighting those with peculiar genome structures, such as a split RNA dependent RNA polymerase gene. Next, we delineate notable mycovirus-mediated phenotypes in Aspergillus , in particular reporting on observations of mycoviruses that affect their fungal host's virulence and explore how this may relate to virus-mediated decreased stress tolerance. Furthermore, mycovirus effects on microbial competition and antifungal resistance are discussed. The factors that influence the manifestation of these phenotypes, such as temperature, fungal life stage, and infection with multiple viruses, among others, are also evaluated. In addition, we attempt to elucidate the molecular mechanisms that underpin these phenotypes, examining how mycoviruses can be targets, triggers, and even suppressors of RNA silencing and how this can affect fungal gene expression and phenotypes. Finally, we highlight the potential therapeutic applications of mycoviruses and how, in an approach analogous to bacteriophage therapy, their ability to produce hypovirulence in Aspergillus might be used to attenuate invasive aspergillosis infections in humans.

Background: Sleeve gastrectomy (SG) increased in popularity after 2010 but recent data suggest it has concerning rates of gastroesophageal reflux and need for conversions. This study aims to evaluate recent trends in the utilization of bariatric procedures, associated complications, and conversions using an administrative claims database in the United States., Methods: We included adults who had bariatric procedures from 2000 to 2020 with continuous enrollment for at least 6 months in the MarketScan Commercial Claims and Encounters database. Index bariatric procedures and subsequent revisions or conversions were identified using CPT codes. Baseline comorbidities and postoperative complications were identified with ICD-9-CM and ICD-10 codes. Cumulative incidences of complications were estimated at 30-days, 6-months, and 1-year and compared with stabilized inverse probability of treatment weighted Kaplan-Meier analysis., Results: We identified 349,411 bariatric procedures and 5521 conversions or revisions. The sampled SG volume appeared to begin declining in 2018 while Roux-en-Y gastric bypass (RYGB) remained steady. Compared to RYGB, SG was associated with lower 1-year incidence [aHR, (95% CIs)] for 30-days readmission [0.65, (0.64-0.68)], dehydration [0.75, (0.73-0.78)], nausea or vomiting [0.70, (0.69-0.72)], dysphagia [0.55, (0.53-0.57)], and gastrointestinal hemorrhage [0.43, (0.40-0.46)]. Compared to RYGB, SG was associated with higher 1-year incidence [aHR, (95% CIs)] of esophagogastroduodenoscopy [1.13, (1.11-1.15)], heartburn [1.38, (1.28-1.49)], gastritis [4.28, (4.14-4.44)], portal vein thrombosis [3.93, (2.82-5.48)], and hernias of all types [1.36, (1.34-1.39)]. There were more conversions from SG to RYGB than re-sleeving procedures. SG had a significantly lower 1-year incidence of other non-revisional surgical interventions when compared to RYGB., Conclusions: The overall volume of bariatric procedures within the claims database appeared to be declining over the last 10 years. The decreasing proportion of SG and the increasing proportion of RYGB suggest the specific complications of SG may be driving this trend. Clearly, RYGB should remain an important tool in the bariatric surgeon's armamentarium., (© 2024. The Author(s).)

Office hours are an integral component of science, technology, engineering, and math (STEM) courses at nearly all colleges and universities. Despite their ubiquity as a support mechanism, there has only been limited work examining how instructors approach office hours and what shapes these approaches. Here, we conduct a phenomenographic study to investigate how instructors of STEM courses experience office hours and how these experiences may impact their approaches to promoting and managing office hours. We identified variations in how instructors promoted office hours, the modality of office hours (i.e., when and where office hours were held), and how instructors facilitated learning during office hours. These variations spanned from student-centric (strategies instructors use with students' interest in mind, e.g., wanting to increase student learning, accessibility, comfort, etc.) to instructor-centric (strategies the instructors use with their own self-interest in mind, e.g., saving time and/or bandwidth, personal needs, comfort, etc.). Additionally, we identify several challenges and barriers, including a lack of formal training or opportunities to discuss office hour approaches with other faculty, and conclude with general recommendations for instructors and administrators in STEM departments for engaging and supporting students during office hours., Competing Interests: Conflicts of interest: The authors declare no conflicts of interest.

Background: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory demyelinating disease characterized by relapsing clinical episodes and the presence of autoantibodies. The impact of comorbidities on relapsing rate of NMOSD patients in Taiwan remains unclear., Methods: We conducted a longitudinal retrospective study using the largest hospital system in Taiwan from 2006 to 2021. Demographic characteristics, annualized relapse rates (ARR), and comorbidities were examined., Results: We identified 485 NMOSD patients from 2006 to 2021. Of these, 466 had the adult form and 19 (3.9 %) had the pediatric form of NMOSD. The median ARR was 0.51 (interquartile range (IQR): 0.26-1.11) for adults and 0.39 (IQR: 0.21-0.77) for pediatric patients. Comorbidities included malignancy (6.7 %) and autoimmune diseases (21.7 %). The recommended age for malignancy surveillance in NMOSD patients was 43.3 years. Neither malignancy nor autoimmune disease increased the ARR within 3 years post diagnosis in NMOSD patients with comorbidities compared with those without comorbidities., Conclusions: Our study revealed the ARR within the initial three years after diagnosis was significantly higher, emphasizing the importance of early treatment. We also observed an association between malignancy and NMOSD, and a significantly higher risk of malignancy in adult patients with NMOSD than in the general population (the relative risk was 5.99) that requiring further investigations into the underlying mechanisms. These findings contribute to a better understanding of NMOSD and its comorbidities in Taiwan., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest. All author that there's no financial/personal interest or belief that could affect their objectivity, or if there is, stating the source and nature of that potential conflict., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Post-traumatic stress disorder (PTSD) occurs when an individual experiences a traumatic event that exceeds the limits of psychological endurance. Many veterans experience PTSD. PTSD can negatively impact veterans' quality of life, functioning, life satisfaction, and overall well-being. It is important to analyze the concept of PTSD in the veteran population. This concept analysis aimed to investigate the defining attributes, a model case, antecedents, consequences, and empirical referents related to the concept of PTSD among veterans. Walker and Avant's method was used to guide this concept analysis of PTSD. The results showed that three attributes were determined from the analysis: intrusive memories of traumatic events, feelings of isolation and estrangement, and negative cognitions. PTSD is conceptualized as a collection of symptoms that arise from highly traumatic experiences. The military environment predisposes veterans to traumatic events that should be identified or acknowledged. A better understanding of the concept of PTSD can facilitate the development of effective interventions for the veteran population and enhance their mental health.

Existing research has investigated student problem-solving strategies across science, technology, engineering, and mathematics; however, there is limited work in undergraduate biology education on how various aspects that influence learning combine to generate holistic approaches to problem solving. Through the lens of situated cognition, we consider problem solving as a learning phenomenon that involves the interactions between internal cognition of the learner and the external learning environment. Using phenomenography as a methodology, we investigated undergraduate student approaches to problem solving in biology through interviews. We identified five aspects of problem solving (including knowledge, strategy, intention, metacognition, and mindset) that define three qualitatively different approaches to problem solving; each approach is distinguishable by variations across the aspects. Variations in the knowledge and strategy aspects largely aligned with previous work on how the use or avoidance of biological knowledge informed both concept-based and nonconcept-based strategies. Variations in the other aspects revealed intentions spanning complete disengagement to deep interest with the course material, different degrees of metacognitive reflections, and a continuum of fixed to growth mindsets. We discuss implications for how these characterizations can improve instruction and efforts to support development of problem-solving skills.

Background: Progressive supranuclear palsy (PSP) is a tauopathy that involves subcortical regions but also extends to cortical areas. The clinical impact of different tau protein sites and their influence on glymphatic dysfunction have not been investigated., Patients and Methods: Participants (n = 55; 65.6 ± 7.1 years; 29 women) with PSP (n = 32) and age-matched normal controls (NCs; n = 23) underwent 18 F-Florzolotau tau PET, MRI, PSP Rating Scale (PSPRS), and Mini-Mental State Examination. Cerebellar gray matter (GM) and parametric estimation of reference signal intensity were used as references for tau burden measured by SUV ratios. Glymphatic activity was measured by diffusion tensor image analysis along the perivascular space (DTI-ALPS)., Results: Parametric estimation of reference signal intensity is a better reference than cerebellar GM to distinguish tau burden between PSP and NCs. PSP patients showed higher cortical and subcortical tau SUV ratios than NCs ( P < 0.001 and <0.001). Cortical and subcortical tau deposition correlated with PSPRS, UPDRS, and Mini-Mental State Examination scores (all P 's < 0.05). Cortical tau deposition was further associated with the DTI-ALPS index and frontal-temporal-parietal GM atrophy. The DTI-ALPS indexes showed a significantly negative correlation with the PSPRS total scores ( P < 0.01). Finally, parietal and occipital lobe tau depositions showed mediating effects between the DTI-ALPS index and PSPRS score., Conclusions: Cortical tau deposition is associated with glymphatic dysfunction and plays a role in mediating glymphatic dysfunction and clinical severity. Our results provide a possible explanation for the worsening of clinical severity in patients with PSP., Competing Interests: Conflicts of interest sources of funding: T.C.Y. owns equity in APRINOIA Therapeutics. The other authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Metastatic castration-resistant prostate cancer (CRPC), the most refractory prostate cancer, inevitably progresses and becomes unresponsive to hormone therapy, revealing a pressing unmet need for this disease. Novel agents targeting HDAC6 and microtubule dynamics can be a potential anti-CRPC strategy., Methods: Cell proliferation was examined in CRPC PC-3 and DU-145 cells using sulforhodamine B assay and anchorage-dependent colony formation assay. Flow cytometric analysis of propidium iodide staining was used to determine cell-cycle progression. Cell-based tubulin polymerization assay and confocal immunofluorescence microscopic examination determine microtubule assembly/disassembly status. Protein expressions were determined using Western blot analysis., Results: A total of 82 novel derivatives targeting HDAC6 were designed and synthesized, and Compound 25202 stood out, showing the highest efficacy in blocking HDAC6 (IC 50 , 3.5 nM in enzyme assay; IC 50 , 1.0 μM in antiproliferative assay in CRPC cells), superior to tubastatin A (IC 50 , 5.4 μM in antiproliferative assay). The selectivity and superiority of 25202 were validated by examining the acetylation of both α-tubulin and histone H3, detecting cell apoptosis and HDACs enzyme activity assessment. Notably, 25202 but not tubastatin A significantly decreased HDAC6 protein expression. 25202 prolonged mitotic arrest through the detection of cyclin B1 upregulation, Cdk1 activation, mitotic phosphoprotein levels, and Bcl-2 phosphorylation. Compound 25202 did not mimic docetaxel in inducing tubulin polymerization but disrupted microtubule organization. Compound 25202 also increased the phosphorylation of CDC20, BUB1, and BUBR1, indicating the activation of the spindle assembly checkpoint (SAC). Moreover, 25202 profoundly sensitized cisplatin-induced cell death through impairment of cisplatin-evoked DNA damage response and DNA repair in both ATR-Chk1 and ATM-Chk2 pathways., Conclusion: The data suggest that 25202 is a novel selective and potent HDAC6 inhibitor. Compound 25202 blocks HDAC6 activity and interferes microtubule dynamics, leading to SAC activation and mitotic arrest prolongation that eventually cause apoptosis of CRPC cells. Furthermore, 25202 sensitizes cisplatin-induced cell apoptosis through impeding DNA damage repair pathways., (© 2024 Wiley Periodicals LLC.)

Bariatric surgery is currently the most effective long-term treatment for morbid obesity as well as type-2 diabetes mellitus. The field of metabolic and bariatric surgery has seen tremendous growth over the past decade with dramatically reduced risks. This article aims to provide an update on bariatric surgery, highlighting the latest outcomes, improvements, and challenges in the field. Recently, the American Society of Metabolic and Bariatric Surgery (ASMBS) and the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) released a major update to the indications for bariatric surgery at BMI ≥35 kg/m 2 regardless of co-morbidities and 30-34.9 kg/m 2 with obesity-related comorbidities. Sleeve gastrectomy has emerged as the most popular bariatric procedure in the last 10 years with its remarkable efficacy and safety profile. The implementation of the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) and Enhanced Recovery After Surgery (ERAS) protocols have significantly improved the quality of care for all bariatric patients. The recent introduction and FDA approval of Glucagon-Like Peptide-1 (GLP-1) agonists for chronic obesity has garnered significant media coverage and popularity, but no guidelines exist regarding its use in relation to bariatric surgery. This update underscores the need for tailored approaches, ongoing research, and the integration of evidence-based medicine and innovations to enhance patient care., 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.

We present a weeklong curricular module for high school biology students that promotes knowledge of phytohormones, the circadian clock, and the Central Dogma. The module, which relies on easily accessible items and requires minimal space, integrates a hands-on experiment that guides students through replicating research examining circadian entrainment in postharvest cabbage from groceries. This work found that plants have cyclical, circadian expression of genes that produce phytohormones, and that such cyclical expression influences herbivory by caterpillars. Such cyclical patterns were found in plants both in situ and in postharvest cabbage. This work thus provides an ideal platform to shape student conceptions of circadian rhythms, gene expression, and plant herbivory by having students use light timers to entrain postharvest cabbage to alternating light and dark cycles and then measuring herbivory in these plants. The results should replicate previous work and demonstrate less herbivory when both plant and caterpillar are entrained to the same light and dark cycles since the expression of phytohormones involved in plant defense will be greatest when caterpillars are active. The module then concludes with a discussion of gene regulation and how this influences phytohormones. This module was field tested at four public schools, reaching over 600 students, and we present data demonstrating that the module led to learning gains and likely increases in interest in plant biology and self-efficacy., Competing Interests: The authors declare no conflict of interest.

Typically, bioactive peptides were uncovered from complex hydrolysates using sequential bioassay-guided fractionation. To increase the efficiency of bioactive peptide screening, a simple and convenient tandem bioassay-guided fractionation based on solid-phase extraction (SPE) was conducted to screen the angiotensin-I-converting enzyme (ACE) inhibitory peptides from the hydrolysate of Inca nut cake protein (INCP). The so-called SCX-RP SPE system was constructed by assembling SCX (strong cation exchange) and RP (reversed phase) SPE cartridges. Using this tandem SCX-RP SPE, the INCP digested with combined gastrointestinal protease (INCP GP) was fractionated into 30 fractions. The fraction F11 exhibited the highest ACE inhibitory activity among 30 fractions. The ACE IC 50 of fraction F11 was calculated to be 6.6 ± 0.5 µg/mL. The ACEI activity of fraction F11 was stronger than the INCP GP hydrolysate (ACE IC 50 of 12.7 ± 0.4 µg/mL). The tandem SCX-RP SPE fractionation reduced the number of ACE inhibitory (ACEI) peptide candidates from 127 peptides in the INCP GP hydrolysate to only ten peptides in fraction F11. Subsequently, WALPTQSW (WW-8) and WLPTKSW (WW-7) from fraction F11 were synthesized, and their ACE IC 50 was determined to be 4.7 ± 0.1 and 7.9 ± 0.1 µM, respectively. The dipeptidyl peptidase-4 (DPP4) inhibitory and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activities of WALPTQSW (WW-8) were also explored to give IC 50 values of 131.7 ± 5.2 and 191.8 ± 7.0 µM, respectively. The molecular docking and inhibition mechanism studies indicated that WW-8 inhibited ACE and DPP4 as competitive and non-competitive inhibitors, respectively. The pre-incubation experiment of WW-8 toward ACE and DPP4 demonstrated that WW-8 was a true-inhibitor type. Additionally, the amount of WW-8 was quantified to be 5.8 ± 0.2 and 35 ± 0.4 µg per milligram hydrolysate and fraction F11, respectively. This study demonstrated tandem bioassay-guided SCX-RP SPE fractionation efficiently screened ACEI peptide derived from INCP GP hydrolysate, adding more value to Inca nut cake (a leftover of the oil industry) as a bioactive peptide precursor., 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 © 2024 Elsevier B.V. All rights reserved.)

Various vaccines have been developed in response to the SARS-CoV-2 pandemic, and the safety of vaccines has become an important issue. COVID-19 vaccine-related central nervous system inflammatory demyelinating diseases (CNS IDDs) have been reported recently. We present one case of AstraZeneca vaccine-related myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease and a literature review of another 78 patients published from January 2020 to October 2022. Patients were divided into three vaccine types (viral vector, mRNA, and inactivated vaccines) for further analyses. Among 79 patients with COVID-19 vaccine-related CNS IDDs, 49 (62%) cases received viral vector vaccines, 20 (25.3%) received mRNA vaccines, and 10 (12.7%) received inactivated vaccines. Twenty-seven cases (34.2%) were confirmed with autoantibodies, including fifteen patients (19%) with anti-MOG, eleven (13.9%) with anti-aquaporin 4 (AQP4), and one (1.3%) with both antibodies. Significantly, more males developed CNS IDDs post viral vector vaccines compared to mRNA and inactivated vaccines. Patients receiving mRNA vaccines were older than those receiving other types. Furthermore, mRNA and inactivated vaccines correlated more with anti-AQP4 antibodies, while viral vector vaccines showed higher MOG positivity. This research suggests potential associations between COVID-19 vaccine-related CNS IDDs and gender, age, and autoantibodies, contingent on vaccine types. Protein sequence analysis implies similarities between the S protein and AQP4/MOG. Further studies may elucidate the mechanisms of CNS IDDs, aiding vaccine selection for specific types.

Background: Wearable devices have the advantage of always being with individuals, enabling easy detection of their movements. Smart clothing can provide feedback to family caregivers of older adults with disabilities who require in-home care., Methods: This study describes the process of setting up a smart technology-assisted (STA) home-nursing care program, the difficulties encountered, and strategies applied to improve the program. The STA program utilized a smart-vest, designed specifically for older persons with dementia or recovering from hip-fracture surgery. The smart-vest facilitated nurses' and family caregivers' detection of a care receiver's movements via a remote-monitoring system. Movements included getting up at night, time spent in the bathroom, duration of daytime immobility, leaving the house, and daily activity. Twelve caregivers of older adults and their care receiver participated; care receivers included persons recovering from hip fracture (n = 5) and persons living with dementia (n = 7). Data about installation of the individual STA in-home systems, monitoring, and technical difficulties encountered were obtained from researchers' reports. Qualitative data about the caregivers' and care receivers' use of the system were obtained from homecare nurses' reports, which were explored with thematic analysis., Results: Compiled reports from the research team identified three areas of difficulty with the system: incompatibility with the home environment, which caused extra hours of manpower and added to the cost of set-up and maintenance; interruptions in data transmissions, due to system malfunctions; and inaccuracies in data transmissions, due to sensors on the smart-vest. These difficulties contributed to frustration experienced by caregivers and care receivers., Conclusions: The difficulties encountered impeded implementation of the STA home nursing care. Each of these difficulties had their own unique problems and strategies to resolve them. Our findings can provide a reference for future implementation of similar smart-home systems, which could facilitate ease-of-use for family caregivers., (© 2024. The Author(s).)

Lung cancer is the leading cause of cancer-related death worldwide, and ~85% of lung cancers are non-small cell lung cancer (NSCLC), which has a low 5-year overall survival rate and high mortality. Several therapeutic strategies have been developed, such as targeted therapy, immuno-oncotherapy and combination therapy. However, the low survival rate indicates the urgent need for new NSCLC treatments. Vasculogenic mimicry (VM) is an endothelial cell-free tumor blood supply system of aggressive and metastatic tumor cells present during tumor neovascularization. VM is clinically responsible for tumor metastasis and resistance, and is correlated with poor prognosis in NSCLC, making it a potential therapeutic target. In the present study, A549 cells formed glycoprotein-rich lined tubular structures, and transcript levels of VM-related genes were markedly upregulated in VM-forming cells. Based on a drug repurposing strategy, it was demonstrated that doxazosin (an antihypertensive drug) displayed inhibitory activity on VM formation at non-cytotoxic concentrations. Doxazosin significantly reduced the levels of vascular endothelial growth factor A (VEGF-A) and matrix metalloproteinase-2 (MMP-2) in the cell media during VM formation. Further experiments revealed that the protein expression levels of VEGF-A and vascular endothelial-cadherin (VE-cadherin), which contribute to tumor aggressiveness and VM formation, were downregulated following doxazosin treatment. Moreover, the downstream signaling Ephrin type-A receptor 2 (EphA2)/AKT/mTOR/MMP/Laminin-5γ2 network was inhibited in response to doxazosin treatment. In conclusion, the present study demonstrated that doxazosin displayed anti-VM activity in an NSCLC cell model through the downregulation of VEGF-A and VE-cadherin levels, and the suppression of signaling pathways related to the receptor tyrosine kinase, EphA2, protein kinases, AKT and mTOR, and proteases, MMP-2 and MMP-9. These results support the add-on anti-VM effect of doxazosin as a potential agent against NSCLC., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Hsu et al.)

Blood-based biomarkers (BBM) are potentially powerful tools that assist in the biological diagnosis of Alzheimer's disease (AD) in vivo with minimal invasiveness, relatively low cost, and good accessibility. This review summarizes current evidence for using BBMs in AD, focusing on amyloid, tau, and biomarkers for neurodegeneration. Blood-based phosphorylated tau and the Aβ42/Aβ40 ratio showed consistent concordance with brain pathology measured by CSF or PET in the research setting. In addition, glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are neurodegenerative biomarkers that show the potential to assist in the differential diagnosis of AD. Other pathology-specific biomarkers, such as α-synuclein and TAR DNA-binding protein 43 (TDP-43), can potentially detect AD concurrent pathology. Based on current evidence, the working group from the Taiwan Dementia Society (TDS) achieved consensus recommendations on the appropriate use of BBMs for AD in clinical practice. BBMs may assist clinical diagnosis and prognosis in AD subjects with cognitive symptoms; however, the results should be interpreted by dementia specialists and combining biochemical, neuropsychological, and neuroimaging information. Further studies are needed to evaluate BBMs' real-world performance and potential impact on clinical decision-making., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Southern California is a diverse region that is home to a high concentration of food science companies, with an increasing demand for additional food scientists and technologists to join this workforce. Despite this abundance of food science companies and the high demand for jobs, there is currently a shortage in the number of qualified food scientists and technologists in the region. This shortage is also observed within higher education, with declining enrollments in the food science graduate and undergraduate programs across Southern California. Here, we conduct a case study to explore the factors that influence students from Southern California to pursue or not pursue careers in food science. We surveyed both undergraduate and graduate students currently enrolled in food science as well as industry professionals in the region to determine sources of knowledge about the discipline, and motivations and barriers for pursuing careers in food science. We also surveyed high school educators in the region to gain additional perspectives on how food science is being introduced at the secondary level, if at all. Our results demonstrate that many students and high school educators are not knowledgeable about career options within food science and that students who are pursuing food science largely report similar motivations for pursuing the discipline as those currently working in the food science industry. We conclude by discussing implications for the food science education community within Southern California and beyond., (© 2023 The Authors. Journal of Food Science published by Wiley Periodicals LLC on behalf of Institute of Food Technologists.)

Hydrocephalus is routinely treated with ventriculoperitoneal shunt drainage of cerebrospinal fluid (CSF), a procedure plagued by high morbidity and frequent revisions. Vascularized submental lymph node (VSLN) transplants act as lymphatic pumps to drain interstitial fluid (ISF) from lymphedematous extremities. As the field of neuro-lymphatics comes to fruition, we hypothesize the efficacy of VSLN in the drainage of intracranial CSF-ISF. We report novel placement of VSLN in the temporal subdural space in two patients diagnosed with symptomatic communicating hydrocephalus. At a minimum follow-up of 1 month postoperatively, both experienced radiological and clinical improvements., (© 2023 Wiley Periodicals LLC.)

Background: Thiazide-associated hyponatremia (TAH) has been supposed to increase the risk of major adverse cardiovascular events (MACE) in the elderly. Therefore, this study aimed to evaluate the association of TAH with the risk of MACE in elderly Taiwanese patients., Methods: Data from the longitudinal generation tracking database (LGTD 2010) of the Health and Welfare Data Science Center (HWDC) were retrospectively assessed. The TAH study group was defined as using > 30 cumulative daily defined doses (CDDDs) thiazide diuretics within one year before diagnosis of hyponatremia. The control group (1:3 propensity score matching) had no diagnosis of hyponatremia but had used > 30 CDDDs thiazide diuretics within one year. Data on MACE were extracted using International Classification of Diseases codes. Outcomes were assessed using a multivariable Cox proportional hazard model and Kaplan-Meier analysis., Results: A total of 1155 and 3465 individuals were enrolled in the TAH and the control groups, respectively. The rates of MACE (11.1% vs. 7.3%) and death (22.8% vs.12.2%) were significantly higher in the TAH group than the control group. In the TAH group, the adjusted HRs were 1.29 (CI 1.01 ‒ 1.65) for MACE, 1.39 (CI 1.19 ‒ 1.63) for all-cause death, and 1.61 (CI 0.90 ‒ 2.92) for stroke., Conclusion: TAH in patients above 65-years-old is associated with a 29% higher risk of MACE, 39% higher risk of all-cause death, and 61% higher risk of stroke. This work suggests that thiazides prescription in elderly patients should be more careful. However, further research is required to confirm our findings., (© 2023. The Author(s).)

Background: Castration-resistant prostate cancer (CRPC) is refractory to hormone treatment and the therapeutic options are continuously advancing. This study aims to discover the anti-CRPC effects and underlying mechanisms of small-molecule compounds targeting topoisomerase (TOP) II and cellular components of DNA damage repair., Methods: Cell proliferation was determined in CRPC PC-3 and DU-145 cells using anchorage-dependent colony formation, sulforhodamine B assay and flow cytometric analysis of CFSE staining. Flow cytometric analyses of propidium iodide staining and JC-1 staining were used to examine the population of cell-cycle phases and mitochondrial membrane potential, respectively. Nuclear extraction was performed to detect the nuclear localization of cellular components in DNA repair pathways. Protein expressions were determined using Western blot analysis., Results: A series of azathioxanthone-based derivatives were synthesized and examined for bioactivities in which WC-A13, WC-A14, WC-A15, and WC-A16 displayed potent anti-CRPC activities in both PC-3 and DU-145 cell models. These WC-A compounds selectively downregulated both TOP IIα and TOP IIβ but not TOP I protein expression. WC-A13, WC-A14, and WC-A15 were more potent than WC-A16 on TOP II inhibition, mitochondrial dysfunction, and induction of caspase cascades indicating the key role of amine-containing side chain of the compounds in determining anti-CRPC activities. Furthermore, WC-A compounds induced an increase of γH2AX and activated ATR-Chk1 and ATM-Chk2 signaling pathways. P21 protein expression was also upregulated by WC-A compounds in which WC-A16 showed the least activity. Notably, WC-A compounds exhibited different regulation on Rad51, a major protein in homologous recombination of DNA in double-stranded break repair. WC-A13, WC-A14, and WC-A15 inhibited, whereas WC-A16 induced, the nuclear translocation of Rad51., Conclusion: The data suggest that WC-A compounds exhibit anti-CRPC effects through the inhibition of TOP II activities, leading to mitochondrial stress-involved caspase activation and apoptosis. Moreover, WC-A13, WC-A14, and WC-A15 but not WC-A16 display inhibitory activities of Rad51-mediated DNA repair pathway which may increase apoptotic effect of CRPC cells., (© 2023 Wiley Periodicals LLC.)

Nearly all undergraduate biology courses rely on quizzes and exams. Despite their prevalence, very little work has been done to explore how the framing of assessment questions may influence student performance and affect. Here, we conduct a quasi-random experimental study where students in different sections of the same course were given isomorphic questions that varied in their framing of experimental scenarios. One section was provided a description using the self-referential term "you", placing the student in the experiment; another section received the same scenario that used classmate names; while a third section's scenario integrated counterstereotypical scientist names. Our results demonstrate that there was no difference in performance throughout the semester between the sections, nor were there differences in students' self-reported stress and identity. However, students in all three sections indicated that they most preferred the self-referential framing, providing a variety of reasons that suggest that these variants may influence how well a student reads and processes the question. In addition, our results also indicate that the framing of these scenarios can also have a large impact on some students' affect and attitude toward the question. We conclude by discussing implications for the biology education research community and biology instructors.

The hydrolysate of bitter gourd seed protein, digested by the combined gastrointestinal proteases (BGSP-GPs), exhibited the most potent inhibition on angiotensin-I-converting enzyme (ACE) with an IC 50 value of 48.1 ± 2.0 µg/mL. Using two independent bioassay-guided fractionations, fraction F5 from reversed-phase chromatography and fraction S1 from strong cation exchange chromatography exhibited the highest ACE inhibitory (ACEI) activity. Three identical peptides were simultaneously detected from both fractions and, based on the in silico appraisal, APLVSW (AW6) was predicted as a promising ACEI peptide. Their dipeptidyl peptidase-IV (DPP4) inhibitory (DPP4I) activity was also explored. The IC 50 values of AW6 against ACE and DPP4 were calculated to be 9.6 ± 0.3 and 145.4 ± 4.4 µM, respectively. The inhibitory kinetics and intermolecular interaction studies suggested that AW6 is an ACE competitive inhibitor and a DPP4 non-competitive inhibitor. The quantities of AW6 in BGSP-GP hydrolysate, fractions F5 and S1, were also analyzed using liquid chromatography-tandem mass spectrometry. Notably, AW6 could resist hydrolysis in the human gastrointestinal tract according to the result of the simulated gastrointestinal digestion. To the best of our knowledge, this is the first discovery and characterization of a dual-function (ACEI and DPP4I activities) peptide derived from bitter gourd seed protein.

Introduction: The risk, cost, and adverse outcomes associated with packed red blood cell (RBC) transfusions in patients with cardiopulmonary failure requiring extracorporeal membrane oxygenation (ECMO) have raised concerns regarding the overutilization of RBC products. It is, therefore, necessary to establish optimal transfusion criteria and protocols for patients supported with ECMO. The goal of this study was to establish specific criteria for RBC transfusions in patients undergoing ECMO., Methods: This was a retrospective cohort study conducted at Stanford University Hospital. Data on RBC utilization during the entire hospital stay were obtained, which included patients aged ≥18 years who received ECMO support between 1 January 2017, and 30 June 2020 ( n = 281). The primary outcome was in-hospital mortality., Results: Hemoglobin (HGB) levels >10 g/dL before transfusion did not improve in-hospital survival. Therefore, we revised the HGB threshold to ≤10 g/dL to guide transfusion in patients undergoing ECMO. To validate this intervention, we prospectively compared the pre- and post-intervention cohorts for in-hospital mortality. Post-intervention analyses found 100% compliance for all eligible records and a decrease in the requirement for RBC transfusion by 1.2 units per patient without affecting the mortality., Conclusions: As an institution-driven value-based approach to guide transfusion in patients undergoing ECMO, we lowered the threshold HGB level. Validation of this revised intervention demonstrated excellent compliance and reduced the need for RBC transfusion while maintaining the clinical outcome. Our findings can help reform value-based healthcare in this cohort while maintaining the outcome., 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.

Background: There is a paucity of data comparing open, robotic, and laparoscopic approaches on unilateral, non-recurrent inguinal hernias. Our study presents a large, retrospective triple-arm outcome analysis between robotic, laparoscopic, and open unilateral, non-recurrent inguinal hernia repairs at a single institution., Methods: 706 patients who underwent elective, non-recurrent inguinal hernia repair performed by 8 general surgeons at a single institution from 2016 to 2019 were reviewed retrospectively. Patient baseline characteristics, operative times, resident involvement, and postoperative outcomes were analyzed for all repair types. A cost analysis of the different procedures was performed., Results: There were 305 laparoscopic repairs, 207 robotic repairs, and 194 open repairs. Open and laparoscopic repairs were performed on patients who were older (p =< .001) and with a higher Charlson Comorbidity Index (p =< .001). Patient BMI was higher in minimally invasive repair than open repair (P = .021). There were no significant differences in complication rates on pairwise analysis. Robotic and open repairs had significantly longer operative times than laparoscopic repairs (P < .001). There was less resident involvement in robotic repair than with the other approaches (P < .001). Resident involvement was associated with shorter OR times (P = .001) and no significant difference in postoperative complications. There was a trend over the study period toward faster operative times and more robotic repair. Robotic repair is the most expensive repair, followed by laparoscopic and open repairs., Conclusion: All 3 repair techniques can be performed without significant differences in outcomes. The technique utilized should be based on surgeon preference and patient characteristics., 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.

Immunotherapy, in the form of hematopoietic stem cell transplantation (HSCT), has been part of the standard of care in the treatment of acute leukemia for over 40 years. Trials evaluating novel immunotherapeutic approaches, such as targeting the programmed death-1 (PD-1) pathway, have unfortunately not yielded comparable results to those seen in solid tumors. Major histocompatibility complex (MHC) proteins are cell surface proteins essential for the adaptive immune system to recognize self versus non-self. MHC typing is used to determine donor compatibility when evaluating patients for HSCT. Recently, loss of MHC class II (MHC II) was shown to be a mechanism of immune escape in patients with acute myeloid leukemia after HSCT. Here we report that treatment with the tyrosine kinase inhibitor, dasatinib, and an anti-PD-1 antibody in preclinical models of Philadelphia chromosome positive B-cell acute lymphoblastic leukemia is highly active. The dasatinib and anti-PD-1 combination reduces tumor burden, is efficacious, and extends survival. Mechanistically, we found that treatment with dasatinib significantly increased MHC II expression on the surface of antigen-presenting cells (APC) in a tumor microenvironment-independent fashion and caused influx of APC cells into the leukemic bone marrow. Finally, the induction of MHC II may potentiate immune memory by impairing leukemic engraftment in mice previously cured with dasatinib, after re-inoculation of leukemia cells. In summary, our data suggests that anti-PD-1 therapy may enhance the killing ability of dasatinib via dasatinib driven APC growth and expansion and upregulation of MHC II expression, leading to antileukemic immune rewiring., Competing Interests: Competing interests: PK reports advisory board fees from Novartis, Daiichi Sankyo, BMS, and Ascentage, the speaker’s bureau of Takeda and Novartis, reports participating in the data safety monitoring board with Treadwell Therapeutics, and honoraria with Clinical Care Targeted Communications. PW reports employment from Genentech. MAC reports grants and personal fees from ImmunoGenesis, Inc., personal fees from Alligator Bioscience, Inc., personal fees from ImmunOS, Inc., grants and personal fees from ImmunoMet, Inc., personal fees from Oncoresponse, Inc., personal fees from Pieris, Inc., personal fees from Nurix, Inc., personal fees from Aptevo, Inc., personal fees from Servier, Inc., personal fees from Kineta, Inc., personal fees from Salarius, Inc., personal fees from Xencor, Inc., personal fees from Agenus, Inc., personal fees from Mereo, Inc., personal fees from Amunix, Inc., personal fees from Adagene, Inc., outside the submitted work. In addition, MAC has a patent Methods and Composition for Localized Secretion of Anti-CTLA-4 Antibodies with royalties paid to multiple licensees, a patent Dual specificity antibodies which bind both PD-L1 and PD-L2 and prevent their binding to PD-1 with royalties paid to ImmunoGenesis, Inc., and a patent Cyclic Dinucleotides as Agonists of Stimulator of Interferon Gene Dependent Signaling licensed to ImmunoGenesis, Inc. MK reports grants from Ablynx, Agios, Ascentage, AstraZeneca, Calithera, Cellectis, Eli Lilly, Rafael Pharmaceutical, and Sanofi; grants and other support from AbbVie, F. Hoffman La-Roche, Forty-Seven, Genentech, and Stemline Therapeutics; and other support from Amgen, Kisoji, Reata Pharmaceutical outside the submitted work; and has a patent (US 7,795,305 B2: “CDDO-Compounds and Combination Therapie”) with royalties paid to Reata Pharm, a patent (“Combination Therapy With a Mutant IDH1 Inhibitor and a BCL-2”) licensed to Eli Lilly, and a patent (62/993,166: Combination of a MCL-1 Inhibitor and Midostaurin, Uses and Pharmaceutical Compositions Thereof”) pending to Novartis. Funding for this work was provided by the Advanced Scholar Program at MD Anderson (2018-2019, Koller), the University of Texas MD Anderson Cancer Center support Grant (CA016672), and the University of Texas MD Anderson–China Medical University and Hospital Sister Institution Network Fund., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The pearl garlic (Allium sativum L.) protein (PGP) was digested using pepsin, trypsin, α-chymotrypsin, thermolysin, and simulated gastrointestinal digestion. The α-chymotrypsin hydrolysate showed the highest angiotensin-I-converting enzyme inhibitory (ACEI) activity, with an IC 50 value of 190.9 ± 11 µg/mL. A reversed-phase C 18 solid-phase extraction (RP-SPE) cartridge was used for the first fractionation, and the S4 fraction from RP-SPE showed the most potent ACEI activity (IC 50 =124.1 ± 11 3 µg/mL). The S4 fraction was further fractionated using a hydrophilic interaction liquid chromatography SPE (HILIC-SPE). The H4 fraction from HILIC-SPE showed the highest ACEI activity (IC 50 =57.7 ± 3 µg/mL). Four ACEI peptides (DHSTAVW, KLAKVF, KLSTAASF, and KETPEAHVF) were identified from the H4 fraction using liquid chromatography-tandem mass spectrometry (LC-MS/MS), and their biological activities were appraised in silico. Among the identified α-chymotryptic peptides, DHSTAVW (DW7), derived from I lectin partial protein, exhibited the most potent ACEI activity (IC 50 value of 2.8 ± 0.1 µM). DW7 was resistant to simulated gastrointestinal digestion, and it was classified as a prodrug-type inhibitor according to the preincubation experiment. The inhibition kinetics indicated that DW7 was a competitive inhibitor, which was rationalized by the molecular docking simulation. The quantities of DW7 in 1 mg of hydrolysate, S4 fraction, and H4 fraction were quantified using LC-MS/MS to give 3.1 ± 0.1, 4.2 ± 0.1, and 13.2 ± 0.1 µg, respectively. The amount of DW7 was significantly increased by 4.2-fold compared with the hydrolysate, which suggested that this method is efficient for active peptide screening., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Postoperative gastrointestinal bleeding (GIB) is a rare but serious complication of bariatric surgery. The recent rise in extended venous thromboembolism regimens as well as outpatient bariatric surgery may increase the risk of postoperative GIB or lead to delay in diagnosis. This study seeks to use machine learning (ML) to create a model that predicts postoperative GIB to aid surgeon decision-making and improve patient counseling for postoperative bleeds., Methods: The Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database was used to train and validate three types of ML methods: random forest (RF), gradient boosting (XGB), and deep neural networks (NN), and compare them with logistic regression (LR) regarding postoperative GIB. The dataset was split using fivefold cross-validation into training and validation sets, in an 80/20 ratio. The performance of the models was assessed using area under the receiver operating characteristic curve (AUROC) and compared with the DeLong test. Variables with the strongest effect were identified using Shapley additive explanations (SHAP)., Results: The study included 159,959 patients. Postoperative GIB was identified in 632 (0.4%) patients. The three ML methods, RF (AUROC 0.764), XGB (AUROC 0.746), and NN (AUROC 0.741) all outperformed LR (AUROC 0.709). The best ML method, RF, was able to predict postoperative GIB with a specificity and sensitivity of 70.0% and 75.4%, respectively. Using DeLong testing, the difference between RF and LR was determined to be significant with p < 0.01. Type of bariatric surgery, pre-op hematocrit, age, duration of procedure, and pre-op creatinine were the 5 most important features identified by ML retrospectively., Conclusions: We have developed a ML model that outperformed LR in predicting postoperative GIB. Using ML models for risk prediction can be a helpful tool for both surgeons and patients undergoing bariatric procedures but more interpretable models are needed., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Teaching undergraduate students to read primary scientific literature (PSL) is cited as an important goal for many science, technology, engineering, and math (STEM) classes, given a range of cognitive and affective benefits for students who read PSL. Consequently, there are a number of approaches and curricular interventions published in the STEM education literature on how to teach students to read PSL. These approaches vary widely in their instructional methods, target student demographic, required class time, and level of assessment demonstrating the method's efficacy. In this Essay , we conduct a systematic search to compile these approaches in an easily accessible manner for instructors, using a framework to sort the identified approaches by target level, time required, assessment population, and more. We also provide a brief review of the literature surrounding the reading of PSL in undergraduate STEM classrooms and conclude with some general recommendations for both instructors and education researchers on future areas of investigation.

Background: Walking entails orchestration of the sensory, motor, balance, and coordination systems, and walking disability is a critical concern after stroke. How and to what extent these systems influence walking disability after stroke and recovery have not been comprehensively studied., Methods: We retrospectively analyzed patients with stroke in the Post-acute care-Cerebrovascular Diseases (PAC-CVD) program. We compared the characteristics of patient groups stratified by their ability to complete the 5-m walk test across various time points of rehabilitation. We then used stepwise linear regression to examine the degree to which each stroke characteristic and functional ability could predict patient gait performance., Results: Five hundred seventy-three patients were recruited, and their recovery of walking ability was defined by the timing of recovery in a 5-m walk test. The proportion of patients who could complete the 5-m walk test at admission, at 3 weeks of rehabilitation, at 6 weeks of rehabilitation, between 7 and 12 weeks of rehabilitation, and who could not complete the 5-m walk test after rehabilitation was 52.2%, 21.8%, 8.7%, 8.7%, and 8.6%, respectively. At postacute care discharge, patients who regained walking ability earlier had a higher chance of achieving higher levels of walking activity. Stepwise linear regression showed that Berg Balance Scale (BBS) (β: 0.011, p < .001), age (β: -0.005, p = .001), National Institutes of Health Stroke Scale (NIHSS) (6a + 6b; β: -0.042, p = .018), Mini-Nutritional assessment (MNA) (β: -0.007, p < .027), and Fugl-Meyer upper extremity assessment (FuglUE) (β: 0.002, p = .047) scores predicted patient's gait speed at discharge., Conclusion: Balance, age, leg strength, nutritional status, and upper limb function before postacute care rehabilitation are predictors of walking performance after stroke., Competing Interests: Conflicts of interest None., (Copyright © 2022 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Molecular evolution-including the neutral theory of molecular evolution-is a major sub-discipline of evolution and is widely taught in undergraduate evolution courses. However, despite its ubiquity, there have not been any previous attempts to compile and review the molecular evolution education literature. Here, we draw upon the framework proposed in a past literature review examining the broader evolution education landscape to conduct a literature review of papers related to molecular evolution education, classifying the contributions of such papers to evolution pedagogy as well as evolution education research. We find that there remains very limited coverage of molecular evolution in the education literature, with existing papers focusing primarily on providing new instructional modules and strategies for teaching molecular evolution. Our work suggests several areas of critical need as well as opportunities to advance evolution education and evolution education research, including compiling instructional goals for the sub-discipline, developing validated assessments, and investigating student thinking related to molecular evolution. We conclude by providing general strategies, advice, and a novel curricular activity for teaching molecular evolution and the neutral theory of molecular evolution., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Monocots are a major taxon within flowering plants, have unique morphological traits, and show an extraordinary diversity in lifestyle. To improve our understanding of monocot origin and evolution, we generate chromosome-level reference genomes of the diploid Acorus gramineus and the tetraploid Ac. calamus, the only two accepted species from the family Acoraceae, which form a sister lineage to all other monocots. Comparing the genomes of Ac. gramineus and Ac. calamus, we suggest that Ac. gramineus is not a potential diploid progenitor of Ac. calamus, and Ac. calamus is an allotetraploid with two subgenomes A, and B, presenting asymmetric evolution and B subgenome dominance. Both the diploid genome of Ac. gramineus and the subgenomes A and B of Ac. calamus show clear evidence of whole-genome duplication (WGD), but Acoraceae does not seem to share an older WGD that is shared by most other monocots. We reconstruct an ancestral monocot karyotype and gene toolkit, and discuss scenarios that explain the complex history of the Acorus genome. Our analyses show that the ancestors of monocots exhibit mosaic genomic features, likely important for that appeared in early monocot evolution, providing fundamental insights into the origin, evolution, and diversification of monocots., (© 2023. The Author(s).)

Introduction: Tau-targeted positron emission tomography (tau-PET) is a potential tool for the differential diagnosis of Alzheimer's disease (AD) and to clarify the distribution of tau deposition. In addition to the quantitative analysis of tau-PET scans, visual reading supports the assessment of tau loading for clinical diagnosis. This study aimed to propose a method for visually interpreting tau-PET using the [ 18 F] Florzolotau tracer and investigate the performance and utility of the visual reading., Materials and Methods: A total number of 46 individuals with 12 cognitively unimpaired subjects (CU), 20 AD patients with mild cognitive impairment (AD-MCI), and 14 AD with dementia (AD-D) patients with both [ 18 F]Florbetapir amyloid PET and [ 18 F]Florzolotau tau PET scans were included. Clinical information, cognitive assessment, and amyloid PET scan results were recorded. For visual interpretation, a modified rainbow colormap was created and a regional tau uptake scoring system was proposed to evaluate the degree of tracer uptake and its spatial distribution within five cortical regions. Each region was scored on a scale of [0, 2] as compared to the background, and that resulted in a global scale range of [0, 10]. Four readers interpreted [ 18 F]Florzolotau PET using the visual scale. The global and regional standardized uptake value ratios (SUVr) were also calculated for analysis., Results: The result indicates the average global visual scores were 0 ± 0 in the CU group, 3.43 ± 3.35 in the AD-MCI group, and 6.31 ± 2.97 in the AD-D group ( p < 0.001). The consensus among the four observers on image scores was high with an intraclass correlation coefficient of 0.880 (95% CI: 0.767-0.936). The average global visual score was significantly associated with global SUVr ( r = 0.884, p < 0.0001) and with the CDR-sum of box ( r = 0.677, p < 0.0001)., Conclusion: The visual reading method generated a visual score of [ 18 F]Florzolotau tau-PET with good sensitivity and specificity to identify AD-D or CU individuals from the other patients. The preliminary result also showed that the global visual scores are significantly and reliably correlated with global cortical SUVr, and associated well with the clinical diagnosis and cognitive performance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lin, Lin, Huang, Chen, Ho, Huang, Hsu, Chang and Hsiao.)