Multivariate analysis of craniodental morphology in mouse-eared bats (Chiroptera, Vespertilionidae, Myotis) from Vietnam.

This study conducted biostatistical multivariate analyses on 23 craniodental morphological measurements from 209 specimens to study interspecific variations amongst 15 bat species of the genus Myotis in Vietnam. Univariate and multivariate analyses demonstrated that the studied species can be divided into four groups as follows: extra-large-sized species (M.chinensis), large-sized species (M.pilosus, M.indochinensis and M.annectans), medium-sized species (M.altarium, M.hasseltii, M.montivagus, M.horsfieldii, M.ater, M.laniger and M.muricola) and small-sized species (M.annamiticus, M.aff.siligorensis, M.rosseti and M.alticraniatus). Our data revealed that the main craniodental features contributing to the variations in distinguishing Myotis species are the width of the anterior palatal, least height of the coronoid process, length of the upper and lower canine-premolar, zygomatic width and width across the upper canines and lower premolar-molar length. Based on patterns of morphological differences, we conducted comparisons between morphometrically closely resembling species pairs and further discussed additional characteristics that are expected to support the taxonomy and systematics of Vietnamese Myotis bats.

Risk Factors for Hospitalization Duration Longer Than 24 Hours Following Percutaneous Radiofrequency Ablation of Liver Tumours.

PURPOSE: Prior studies have described complications of radiofrequency ablation (RFA) of liver tumours. The aim of this study was to identify risk factors for hospitalization duration longer than 24 hours following RFA of liver tumours. METHODS: This retrospective, single-centre study included patients with liver tumours undergoing RFA between October 2017 and July 2020. Medical records were reviewed to collect patient, tumours, and procedure characteristics for each RFA session. The association between potential risk factors and duration of hospitalization (less than or more than 24 hours) was analyzed using univariate and multivariate logistic regressions. RESULTS: Our study included 291 patients (mean age: 65.2 ± 11.2 [standard deviation]; 201 men) undergoing 324 RFA sessions. Sixty-eight sessions (21.0%) resulted in hospitalization of more than 24 hours. Multivariate analysis identified each additional needle insertion per session (OR 1.4; 95% CI [1.1-1.9]; P = .02), RFA performed in segment V (OR 2.8; 95% CI [1.4-5.7]; P = .004), and use of artificial pneumothorax (OR 14.5; 95% CI [1.4-146.0]; P = .02) as potential risk factors. A history of hepatic encephalopathy (OR 2.6; 95% CI [1.1-6.0]; P = .03) was only significant in univariate analysis. Post-hoc, subgroup analysis of patients with hepatocellular carcinoma (69.8%) did not identify other risk factors. CONCLUSION: Risk factors for a hospitalization duration longer than 24 hours include a higher number of needle insertions per session, radiofrequency ablation in segment V, and use of an artificial pneumothorax.

Prevalence and risk factors for impaired activities of daily living in patients with neo-vascular age-related macular degeneration who present for anti-VEGF treatment.

BACKGROUND/OBJECTIVES: To assess the prevalence and correlates of impaired activities of daily living (ADLs) in patients with neovascular age-related macular degeneration (nAMD) who present for anti-vascular endothelial growth factor (VEGF) therapy. METHODS: In a clinic-based cohort of 437 patients with nAMD who presented for anti-VEGF therapy, the Older American Resources and Services Scale (OARS) was administered to assess for impairments in basic, instrumental and total ADL. Logistic regression analyses were conducted to determine odds ratios (OR) and 95% confidence intervals (CI) for factors associated with ADL impairment. RESULTS: The prevalence of impaired basic, instrumental and total ADL was 37.76%, 67.82% and 39.59%, respectively. In multivariate-adjusted models, moderate visual impairment [OR 5.65, 95% CI (2.31-13.83) and blindness [OR 5.43, 95% CI (2.09-14.12)] were associated with greater odds of impaired total ADL. Depressive symptoms [OR 2.08, 95% CI (1.08-4.00)], the presence of any disability [OR 3.16, 95% CI (1.64-0.07)] and never driving [OR 4.00, 95% CI (1.60-10.00)] were also positively associated with total ADL impairment. Better vision-related quality of life (QoL) was inversely associated with impaired instrumental ADL whilst higher health-related QoL scores were associated with decreased odds of total ADL impairment. CONCLUSIONS: There is a high prevalence rate of ADL impairment among nAMD patients presenting for therapy. Visual impairment, never driving, poor physical and mental health increased the odds of experiencing ADL impairment whilst better VRQoL and HRQoL reduced the odds of impairment.

Targeting transcription factors through an IMiD independent zinc finger domain.

Immunomodulatory imide drugs (IMiDs) degrade specific C2H2 zinc finger degrons in transcription factors, making them effective against certain cancers. SALL4, a cancer driver, contains seven C2H2 zinc fingers in four clusters, including an IMiD degron in zinc finger cluster two (ZFC2). Surprisingly, IMiDs do not inhibit growth of SALL4 expressing cancer cells. To overcome this limit, we focused on a non-IMiD degron, SALL4 zinc finger cluster four (ZFC4). By combining AlphaFold and the ZFC4-DNA crystal structure, we identified a potential ZFC4 drug pocket. Utilizing an in silico docking algorithm and cell viability assays, we screened chemical libraries and discovered SH6, which selectively targets SALL4-expressing cancer cells. Mechanistic studies revealed that SH6 degrades SALL4 protein through the CUL4A/CRBN pathway, while deletion of ZFC4 abolished this activity. Moreover, SH6 led to significant 62% tumor growth inhibition of SALL4+ xenografts in vivo and demonstrated good bioavailability in pharmacokinetic studies. In summary, these studies represent a new approach for IMiD independent drug discovery targeting C2H2 transcription factors in cancer.

Nitrile Imines as Peptide and Oligonucleotide Photo-Cross-Linkers in Gas-Phase Ions.

Nitrile imines produced by photodissociation of 2,5-diaryltetrazoles undergo cross-linking reactions with amide groups in peptide-tetrazole (tet-peptide) conjugates and a tet-peptide-dinucleotide complex. Tetrazole photodissociation in gas-phase ions is efficient, achieving ca. 50% conversion with 2 laser pulses at 250 nm. The formation of cross-links was detected by CID-MS3 that showed structure-significant dissociations by loss of side-chain groups and internal peptide segments. The structure and composition of cross-linking products were established by a combination of UV-vis action spectroscopy and cyclic ion mobility mass spectrometry (c-IMS). The experimental absorption bands were found to match the bands calculated for vibronic absorption spectra of nitrile imines and cross-linked hydrazone isomers. The calculated collision cross sections (CCSth) for these ions were related to the matching experimental CCSexp from multipass c-IMS measurements. Loss of N2 from tet-peptide conjugates was calculated to be a mildly endothermic reaction with ΔH0 = 80 kJ mol-1 in the gas phase. The excess energy in the photolytically formed nitrile imine is thought to drive endothermic proton transfer, followed by exothermic cyclization to a sterically accessible peptide amide group. The exothermic nitrile imine reaction with peptide amides is promoted by proton transfer and may involve an initial [3 + 2] cycloaddition followed by cleavage of the oxadiazole intermediate. Nucleophilic groups, such as cysteine thiol, did not compete with the amide cyclization. Nitrile imine cross-linking to 2'-deoxycytidylguanosine was found to be >80% efficient and highly specific in targeting guanine. The further potential for exploring nitrile-imine cross-linking for biomolecular structure analysis is discussed.

Four New Steroidal Saponins from the Roots of Dracaena cambodiana with NO Production Inhibition Activity in LPS Activated RAW 264.7 Cells.

Seven steroidal saponins including three new 16,23-cyclocholestanes (1-3) and one new pregane (4) were isolated from the roots of Dracaena cambodiana Pierre ex Gagnep. Their chemical structures were elucidated to be (23R,25R)-26-O-ß-D-glucopyranosyl-16,23-cyclocholesta-5,17(20)-dien-22-one-3ß,16α,26-triol-3-O-α-L-rhamnopyranosyl-(1→2)-[α-L-rhamnopyranosyl-(1→3)]-ß-D-glucopyranoside (1), (23R,25R)-26-O-ß-D-glucopyranosyl-16,23-cyclocholesta-5,17,20(22)-trien-3ß,22,26-triol-3-O-α-L-rhamnopyranosyl-(1→3)-ß-D-glucopyranoside (2), (23R,25R)-16,23-cyclocholesta-5,16,20(22)-trien-3ß,22,26-triol-3-O-α-L-rhamnopyranosyl-(1→3)-ß-D-glucopyranoside (3), 3ß-[(O-α-L-rhamnopyranosyl-(1→3)-[α-L-rhamnopyranosyl-(1→2)]-ß-D-gluco-pyranosyl)oxy]-pregna-5,17(20)-diene-16-one-20-carboxylic acid 4''''-O-ß-D-glucopyranosylisopentyl ester (4), cambodianoside A (5), diosbulbiside C (6), and diosbulbiside D (7), by IR, HR-ESI-MS, 1D and 2D NMR spectra. Compounds 1 and 4-7 inhibited nitric oxide (NO) production in lipopolysaccharide activated RAW 264.7 cells with IC50 values ranging from 19.03±1.84 to 67.92±3.81 µM, whereas compounds 2 and 3 were inactive with IC50 values over 100 µM.

Comparison of Radiologists and Deep Learning for US Grading of Hepatic Steatosis.

Background Screening for nonalcoholic fatty liver disease (NAFLD) is suboptimal due to the subjective interpretation of US images. Purpose To evaluate the agreement and diagnostic performance of radiologists and a deep learning model in grading hepatic steatosis in NAFLD at US, with biopsy as the reference standard. Materials and Methods This retrospective study included patients with NAFLD and control patients without hepatic steatosis who underwent abdominal US and contemporaneous liver biopsy from September 2010 to October 2019. Six readers visually graded steatosis on US images twice, 2 weeks apart. Reader agreement was assessed with use of κ statistics. Three deep learning techniques applied to B-mode US images were used to classify dichotomized steatosis grades. Classification performance of human radiologists and the deep learning model for dichotomized steatosis grades (S0, S1, S2, and S3) was assessed with area under the receiver operating characteristic curve (AUC) on a separate test set. Results The study included 199 patients (mean age, 53 years ± 13 [SD]; 101 men). On the test set (n = 52), radiologists had fair interreader agreement (0.34 [95% CI: 0.31, 0.37]) for classifying steatosis grades S0 versus S1 or higher, while AUCs were between 0.49 and 0.84 for radiologists and 0.85 (95% CI: 0.83, 0.87) for the deep learning model. For S0 or S1 versus S2 or S3, radiologists had fair interreader agreement (0.30 [95% CI: 0.27, 0.33]), while AUCs were between 0.57 and 0.76 for radiologists and 0.73 (95% CI: 0.71, 0.75) for the deep learning model. For S2 or lower versus S3, radiologists had fair interreader agreement (0.37 [95% CI: 0.33, 0.40]), while AUCs were between 0.52 and 0.81 for radiologists and 0.67 (95% CI: 0.64, 0.69) for the deep learning model. Conclusion Deep learning approaches applied to B-mode US images provided comparable performance with human readers for detection and grading of hepatic steatosis. Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Tuthill in this issue.

Synchronous rectal adenocarcinoma and intestinal mantle cell lymphoma: A case report.

BACKGROUND: Mantle cell lymphoma (MCL) of the gastrointestinal tract is a rare malignancy, accounting for about 0.2% of malignant colorectal tumors. MCL synchronous with rectal adenocarcinoma is extremely rare. We know of only a few cases reported in the literature. We describe the case of a patient with synchronous rectal adenocarcinoma and intestinal MCL. CASE SUMMARY: A 63-year-old man was admitted to our hospital due to abdominal pain and hematochezia over the past month. The patient was diagnosed with middle rectal cancer cT2N0M0 and underwent surgery. However, we found a large tumor in the small intestine during surgery. The patient underwent total mesorectal excision for rectal cancer and resectioning of the ileal segment containing the large mass. Pathology and immunohistochemistry revealed the presence of both rectal adenocarcinoma and pathognomonic MCL stage IIE presenting as multiple lymphomatous polyposis. The patient subsequently underwent RDHAP/RCHOP chemotherapy and was maintained with rituximab. A Positron Emission Tomography and Computed Tomography (PET/CT) scan showed that the disease responded well to treatment without tumor-increased metabolism in the gastrointestinal tract. CONCLUSION: Synchronous rectal adenocarcinoma and intestinal MCL presenting as multiple lymphomatous polyposis are extremely rare. MCL is often discovered fortuitously when rectal cancer is diagnosed. The coexistence of these tumors poses treatment challenges.

Racial, Ethnic, and Gender Differences in the Timing of Initiating the HPV Vaccine in the United States: the Case of Southeast Asian Americans.

Despite the availability of the human papillomavirus (HPV) vaccine, non-Latinx (NL) Southeast Asian Americans have the highest incidence of HPV-associated cervical cancer in the US. Little is known about NL-Southeast Asian Americans' HPV vaccination coverage due to being categorized under the "Asian American" monolith. Therefore, this study uses restricted data from the 2011-2018 National Health and Nutrition Examination Survey (NHANES) to disaggregate NL-Southeast Asian Americans and compare this population's age-specific probabilities of initiating HPV vaccinations to two Asian American subgroups (NL-East Asian and NL-South Asian Americans) and NL-White, NL-Black, and Latinx Americans. Multinomial logistic regression models examine the differences in the timing of initiating the HPV vaccine series, late (ages 13-26) or never, relative to on-time vaccination (by age 12). NL-Southeast Asian Americans are significantly more likely to never vaccinate and to vaccinate late than NL-White, NL-Black, and Latinx Americans, relative to on-time vaccination. NL-Southeast Asian American boys/men are significantly more likely to never initiate the HPV vaccine than Latinx boys/men, relative to on-time vaccination. NL-Southeast Asian American girls/women are significantly more likely to never vaccinate and vaccinate late than NL-White, NL-Black, and Latinx girls/women, relative to on-time vaccination. There are significant gender differences in uptake among all racial and ethnic groups, except among NL-Southeast and NL-East Asian Americans. Disaggregated data on NL-Southeast Asian Americans helps scholars and public health officials uncover health disparities and improve health interventions. Targeted HPV vaccine promotion and services for this population are needed to mitigate current and future health disparities and promote health equity.

What predicts durable symptom relief of uterine fibroids treated with MRI-guided focused ultrasound? A multicenter trial in 8 academic centers.

OBJECTIVE: To identify variables predictive of durable clinical success after MRI-guided focused ultrasound (MRgFUS) treatment of uterine fibroids. MATERIALS AND METHODS: In this prospective, multicenter trial, 99 women with symptomatic uterine fibroids were treated using MRgFUS. Pelvic MRI was obtained at baseline and treatment day. The Uterine Fibroid Symptom-Quality of Life questionnaire was used to calculate a symptom severity score (SSS) at baseline and 6, 12, 24, and 36 months following treatment. Clinical, imaging, and treatment variables were correlated with symptom reduction sustained through the 12- and 24-month time points using univariable and multivariable logistic regression analyses. A novel parameter, the ratio of non-perfused volume to total fibroid load (NPV/TFL), was developed to determine association with durable outcomes. RESULTS: Post-treatment, mean symptom severity decreased at the 6-, 12-, 24-, and 36-month follow-ups (p < 0.001, all time points). In univariable analysis, three variables predicted treatment success (defined by ≥ 30-point improvement in SSS) sustained at both the 12-month and 24-month time points: increasing ratio of NPV/TFL (p = 0.002), decreasing total fibroid load (p = 0.04), and the absence of T2-weighted Funaki type 2 fibroids (p = 0.02). In multivariable analysis, the NPV/TFL was the sole predictor of durable clinical success (p = 0.01). Patients with ratios below 30% had less improvement in SSS and lacked durable clinical response compared with those between 30-79 (p = 0.03) and ≥ 80% (p = 0.01). CONCLUSION: Increased non-perfused volume relative to total fibroid volume was significantly associated with durable reduction of symptoms of abnormal uterine bleeding and bulk bother. CLINICAL RELEVANCE STATEMENT: Patient selection for sustained clinical benefit should emphasize those with likelihood of achieving high ablation ratios, as determined by imaging (e.g., device access, Funaki type) and by considering the total fibroid load, not just the primary symptomatic fibroid. TRIAL REGISTRATION: Clinical trial ID: NCT01285960. KEY POINTS: • Patient selection/treatment approach associated with durable symptom relief in MRI-guided focused ultrasound ablation of uterine fibroids remains unclear. • The ablation ratio, non-perfused volume/total fibroid volume, was positively associated with sustained symptom relief in both bleeding and bulk bother at 1- and 2-year follow-ups. • Selecting patients with imaging features that favor a high ratio of ablation to total fibroid load (including non-targeted fibroids) is the main factor in predicting durability of symptom relief after uterine fibroid treatment.

SALL4B, not targeted by IMiD, is important for SALL4-mediated tumorigenesis.

Oncofetal transcription factor SALL4 is essential for cancer cell survival. 1-5 Recently, several groups reported that immunomodulatory imide drugs (IMiDs) could degrade SALL4 in a proteasome-dependent manner. 6,7 Intriguingly, we observed that IMiDs had no effect on SALL4-positive cancer cells. Further studies demonstrated that IMiDs could only degrade SALL4A, one of the SALL4 isoforms. This finding raises the possibility that SALL4B, the isoform not affected by IMiDs, may be essential for SALL4-mediated cancer cell survival. SALL4B knockdown led to an increase in apoptosis and inhibition of cancer cell growth. SALL4B gain-of-function alone led to liver tumor formation in mice. Our observation that protein degraders can possess isoform-specific effects exemplifies the importance of delineating drug action and oncogenesis at the isoform level to develop more effective cancer therapeutics.

Assessing surface water pollution in Hanoi, Vietnam, using remote sensing and machine learning algorithms.

Rapid urbanization led to significant land-use changes and posed threats to surface water bodies worldwide, especially in the Global South. Hanoi, the capital city of Vietnam, has been facing chronic surface water pollution for more than a decade. Developing a methodology to better track and analyze pollutants using available technologies to manage the problem has been imperative. Advancement of machine learning and earth observation systems offers opportunities for tracking water quality indicators, especially the increasing pollutants in the surface water bodies. This study introduces machine learning with the cubist model (ML-CB), which combines optical and RADAR data, and a machine learning algorithm to estimate surface water pollutants including total suspended sediments (TSS), chemical oxygen demand (COD), and biological oxygen demand (BOD). The model was trained using optical (Sentinel-2A and Sentinel-1A) and RADAR satellite images. Results were compared with field survey data using regression models. Results show that the predictive estimates of pollutants based on ML-CB provide significant results. The study offers an alternative water quality monitoring method for managers and urban planners, which could be instrumental in protecting and sustaining the use of surface water resources in Hanoi and other cities of the Global South.

Monitoring the effects of urbanization and flood hazards on sandy ecosystem services.

Urbanization, storms, and floods have compromised the benefits derived from various types of sand dune landscapes, particularly in developing countries located in humid monsoon tropical regions. One pertinent question is which driving forces have had a dominant impact on the contributions of sand dune ecosystems to human well-being. Has the decline in sand dune ecosystem services (ES) been primarily due to urbanization or flooding hazards? This study aims to address these issues by developing a Bayesian Belief Network (BBN) to analyze six different sand dune landscapes worldwide. The study uses various data types, including multi-temporal and -sensor remote sensing (SAR and optical data), expert knowledge, statistics, and GIS to analyze the trends in sand dune ecosystems. A support tool based on probabilistic approaches was developed to assess changes in ES over time due to the effects of urbanization and flooding. The developed BBN has the potential to assess the ES values of sand dunes during both rainy and dry seasons. The study calculated and tested the ES values in detail over six years (from 2016 to 2021) in Quang Nam province, Vietnam. The results showed that urbanization has led to an increase in the total ES values since 2016, while floods only had a minimal impact on dune ES values during the rainy season. The fluctuations of ES values were found to be more significant due to urbanization than floods. The study's approach can be useful in future research on coastal ecosystems.

Risk factors for poorer quality of life in patients with neovascular age-related macular degeneration: a longitudinal clinic-based study.

BACKGROUND/OBJECTIVES: To examine the risk factors for poor vision-related and health-related quality of life (QoL) in patients with neovascular age-related macular degeneration (nAMD) who present for anti-vascular endothelial growth factor (anti-VEGF) therapy. METHODS: In a clinic-based cohort of 547 nAMD patients who presented for treatment, the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ25), Short-Form 36 (SF-36) and EuroQoL EQ-5D-5L questionnaires were administered to assess vision-related and health-related QoL. Of these, 83 participants were followed up one-year later to provide longitudinal data. RESULTS: Individuals with mild or moderate visual impairment or blindness at baseline had significantly lower NEI-VFQ-25 scores at follow-up. The presence of ≥3 chronic diseases was associated with lower SF-36 mental component scores (MCS) (p = 0.04) and EQ-VAS scores (p = 0.05). Depressive symptoms were associated with significantly lower MCS (p < 0.0001) and EQ-VAS scores (p = 0.02). Individuals with versus without impaired basic activities of daily living (ADLs) exhibited NEI-VFQ-25 and EQ-VAS scores that were 10.96 (p = 0.03) and 0.13 (p = 0.02) points lower. Those with impaired instrumental ADLs scored 11.62 (p = 0.02), 13.13 (p < 0.0001) and 15.8 (p = 0.0012) points lower in the NEI-VFQ-25, SF-36 physical component score and EQ-5D-5L summary score, respectively. CONCLUSIONS: The QoL of nAMD patients is affected by visual acuity as well as patients' medical history, mental health and functional status.

Phytochemical constituents from Elsholtzia ciliata (Thunb.) Hyl. and their nitric oxide production inhibitory activities.

A new megastigmane glycoside, (3S,4R,7E)-megastigma-5,7-diene-9-one-3,4-diol 3-O-ß-D-apiofuranosyl-(1→2)-ß-D-glucopyranoside (1) and a new cyanogenic glycosyl derivative, (S)-2-(6'-O-R-rosmarinoyl-ß-D-glucopyranosyloxy)-phenylacetonitrile (2) were isolated from the methanol extract of the Elsholtzia ciliata together with twelve known compounds, 1-O-ß-D-glucopyranosyl-2-hydroxy-4-allylbenzene (3), citrusin C (4), 1,2-di-O-ß-D-glucopyranosyl-4-allylbenzene (5), manglieside B (6), 4-allyl-2-hydroxyphenyl 1-O-ß-D-apiofuranosyl-(1→6)-ß-D-glucopyranoside (7), (-)-isolariciresinol 3α-ß-D-glucopyranoside (8), 7R,8R-threo-4,7,9-trihydroxy-3,3'-dimethoxy-8-O-4'-neolignan-9'-O-ß-D-glucopyranoside (9), 7R,8R-threo-4,7,9,9'-tetrahydroxy-3-methoxy-8-O-4'-neolignan-9'-O-ß-D-glucopyranoside (10), cedrusin-4-O-ß-D-glucopyranoside (11), icariside E3 (12), everlastoside L (13) and rosmarinic acid (14). Their chemical structures were elucidated on the basic of extensive 1D and 2D-NMR experiments, as well as their mass spectroscopic data. The absolute configurations of the compounds 1 and 2 were successfully indicated by both theoretical and calculated CD spectra. Compounds 3-7, 9 and 10 potential inhibited NO production in LPS-activated RAW264.7 cells with IC50 values of 6.71, 8.97, 12.38, 14.27, 16.13, 13.54, 16.27 µM, respectively, compared to that of the positive control of NG-monomethyl-L-arginine acetate (L-NMMA), IC50 = 32.51 µM.

An Intervention Mapping Approach to Developing a Stroke Literacy Video for Recent Stroke Survivors: Development and Usability Study.

BACKGROUND: Most vascular events after stroke may be prevented by modifying vascular risk factors through medical and behavioral interventions. Stroke literacy-an understanding of stroke symptoms, risk factors, and treatment-likely contributes to vascular risk factor control and in turn stroke recurrence risk. Stroke literacy is the lowest among adults belonging to racial and ethnic minority populations in the United States. Video-based interventions targeting stroke literacy may help acute stroke survivors understand stroke and subsequently reduce the risk of stroke recurrence. However, the failure of prior stroke literacy interventions may be due in part to the fact that the interventions were not theory-driven. Intervention mapping (IM) provides a framework for use in the development, implementation, and evaluation of evidence-informed, health-related interventions. OBJECTIVE: We aimed to develop a video-based educational intervention to improve stroke literacy in hospitalized patients with acute stroke. METHODS: The 6-step iterative process of IM was used to develop a video-based educational intervention and related implementation and evaluation plans. The six steps included a needs assessment, the identification of outcomes and change objectives, the selection of theory- and video-based intervention methods and practical applications, the development of a video-based stroke educational intervention, plans for implementation, and evaluation strategies. RESULTS: A 5-minute video-based educational intervention was developed. The IM approach led to successful intervention development by emphasizing stakeholder involvement, generation and adoption, and information retainment in the planning phase of the intervention. A planned approach to video adoption, implementation, and evaluation was also developed. CONCLUSIONS: An IM approach guided the development of a 5-minute video-based educational intervention to promote stroke literacy among acute stroke survivors. Future studies are needed to assess the use of technology and digital media to support widespread access and participation in video-based health literacy interventions for populations with acute and chronic stroke. Studies are needed to assess the impact of video-based educational interventions that are paired with stroke systems of care optimization to reduce the risk of stroke recurrence. Furthermore, studies on culturally and linguistically sensitive video-based stroke literacy interventions are needed to address known racial and ethnic disparities in stroke literacy. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1371/journal.pone.0171952.

"Functioning better is doing better": older adults' priorities for the evaluation of assistive technology.

Despite the benefits of assistive technology (AT), barriers to technology adoption still exist and are uniquely affecting older populations. Improving technology adoption can be achieved by involving end-users in the development and evaluation process. However, existing AT evaluation tools rarely take into account older adults' experiences. The goal of this study was to fill this gap by determining which AT evaluation criteria are important for older adults. We conducted 4 nominal group meetings with 21 participants aged 50+ in Vancouver, Canada. In the meetings, participants generated AT evaluation criteria and organized them in the order of importance. The content from the meetings was analyzed using qualitative content analysis. Final rankings were collated to reveal which criteria were the most important across the groups. We found that promotion of independence, affordability, ease of use and ethics are the most important AT evaluation criteria for older adults. Some aspects of ATs that older adults value, such as reliability, are not featured in AT evaluation tools. This study provides insight into older adults' priorities for AT evaluation criteria, and concerns that older adults have about AT use. The findings are supplemented with a comprehensive analysis of the group discussions that contextualizes the criteria.

Comparison of In-Hospital Outcomes of Surgical Stabilization of Rib Fractures with Nonsurgical Management: A Multicenter, Prospective, Cohort Study.

Background: Evidence for the efficacy of surgical stabilization of rib fractures in patients with rib fractures is controversial. Objective: We aim to compare the clinical outcomes of surgical rib fixation for rib fracture with non-operative treatment. Methods: Our institutional database from three general hospitals (Viet Duc Hospital, Viet Tiep Friendship Hospital & Cho Ray Hospital) was queried to identify patients with flail chest treated with locked plate fixation between December 2021 and February 2023. A medical record review for demographic, injury, hospital, and surgical data was also retrospectively performed for all patients. Characteristics and outcomes of the patients receiving the surgical rib fixation for rib fracture were compared with those without surgery. Results: A total of 166 patients with thoracic trauma were included. The majority of patients were male, and the age range was from 18 to 80 years old, with a mean age of 51.6 years. 52 (31.3%) underwent surgical stabilization of rib fractures (SSRF). The highest combined injuries were limb injuries, followed by traumatic brain injury, and maxillofacial trauma. While 1 patient died in the non-surgical group, there was no significant difference in the mortality between the two groups. The surgical group had a slightly shorter hospital stay than the non-surgical group (8.6 days vs. 10.0 days, p-value: 0.038). SSRF group tended toward a lower incidence of pneumonia compared to the non-surgical group (SSRF: 3.8% vs. non-surgical: 7%), but this difference was not statistically significant (p-value: 0.426). SSRF group also had a lower incidence of tracheostomy than the non-operative group (SSRF: 0% vs. non-surgical: 1.8%, p-value: 0.337). Conclusion: Operative fixation of a rib fracture in trauma patients resulted in a lower incidence of pneumonia, fewer days of mechanical ventilation, and a shorter hospital stay compared to non-operative treatment group.

The immune landscape of undifferentiated pleomorphic sarcoma.

Introduction: Undifferentiated pleomorphic sarcoma (UPS) can be associated with a relatively dense immune infiltration. Immune checkpoint inhibitors (anti-PD1, anti-PDL1, and anti-CTLA4) are effective in 20% of UPS patients. We characterize the immune microenvironment of UPS and its association with oncologic outcomes. Material and methods: Surgically resected UPS samples were stained by immunohistochemistry (IHC) for the following: tumor-associated immune cells (CD3, CD8, CD163, CD20), immune checkpoints (stimulatory: OX40, ICOS; inhibitory: PD-L1, LAG3, IDO1, PD1), and the adenosine pathway (CD73, CD39). Sections were reviewed for the presence of lymphoid aggregates (LA). Clinical data were retrospectively obtained for all samples. The Wilcoxon rank-sum and Kruskal-Wallis tests were used to compare distributions. Correlations between biomarkers were measured by Spearman correlation. Univariate and multivariate Cox models were used to identify biomarkers associated with overall survival (OS) and disease-free survival (DFS). Unsupervised clustering was performed, and Kaplan-Meier curves and log-rank tests used for comparison of OS and DFS between immune clusters. Results: Samples analyzed (n=105) included 46 primary tumors, 34 local recurrences, and 25 metastases. LA were found in 23% (n=10/43), 17% (n=4/24), and 30% (n=7/23) of primary, recurrent, and metastatic samples, respectively. In primary UPS, CD73 expression was significantly higher after preoperative radiation therapy (p=0.009). CD39 expression was significantly correlated with PD1 expression (primary: p=0.002, recurrent: p=0.004, metastatic: p=0.001), PD-L1 expression (primary: p=0.009), and CD3+ cell densities (primary: p=0.016, recurrent: p=0.043, metastatic: p=0.028). In recurrent tumors, there was a strong correlation between CD39 and CD73 (p=0.015), and both were also correlated with CD163+ cell densities (CD39 p=0.013; CD73 p<0.001). In multivariate analyses, higher densities of CD3+ and CD8+ cells (Cox Hazard Ratio [HR]=0.33; p=0.010) were independently associated with OS (CD3+, HR=0.19, p<0.001; CD8+, HR= 0.33, p=0.010) and DFS (CD3+, HR=0.34, p=0.018; CD8+, HR=0.34, p= 0.014). Unsupervised clustering of IHC values revealed three immunologically distinct clusters: immune high, intermediate, and low. In primary tumors, these clusters were significantly associated with OS (log-rank p<0.0001) and DFS (p<0.001). Conclusion: We identified three immunologically distinct clusters of UPS Associated with OS and DFS. Our data support further investigations of combination anti-PD-1/PD-L1 and adenosine pathway inhibitors in UPS.

Brain-derived neurotrophic factor overexpression in taste buds diminishes chemotherapy induced taste loss.

Vismodegib is used in patients suffering from advanced basal cell carcinoma (BCC), but 100% of the patients taking it report dysgeusia and 50% discontinue the treatment. Treatment with neurotrophic factors can stimulate neuronal survival and functional improvement in injured organs. Here, we analysed novel transgenic mouse lines in which brain-derived neurotrophic factor (BDNF) is overexpressed in taste buds, to examine whether higher levels of BDNF would reduce or prevent negative side effects of vismodegib in the taste system. BDNF plays crucial roles for development, target innervation, and survival of gustatory neurons and taste buds. The behavioural test in this study showed that vehicle-treated wild-type mice prefered 10 mM sucrose over water, whereas vismodegib treatment in wild-type mice caused total taste loss. Gustducin-BDNF mice had a significantly increased preference for low concentration of sucrose solution over water compared to wild-type mice, and most importantly the transgenic mice were able to detect low concentrations of sucrose following vismodegib treatment. We evaluated taste cell morphology, identity, innervation and proliferation using immunohistochemistry. All drug-treated mice exhibited deficits, but because of a possible functional upcycled priming of the peripheral gustatory system, GB mice demonstrated better morphological preservation of the peripheral gustatory system. Our study indicates that overexpression of BDNF in taste buds plays a role in preventing degeneration of taste buds. Counteracting the negative side effects of vismodegib treatment might improve compliance and achieve better outcome in patients suffering from advanced BCC.