Glycerophospholipid remodeling is critical for orthoflavivirus infection.

Flavivirus infection is tightly connected to host lipid metabolism. Here, we performed shotgun lipidomics of cells infected with neurotropic Zika, West Nile, and tick-borne encephalitis virus, as well as dengue and yellow fever virus. Early in infection specific lipids accumulate, e.g., neutral lipids in Zika and some lysophospholipids in all infections. Ceramide levels increase following infection with viruses that cause a cytopathic effect. In addition, fatty acid desaturation as well as glycerophospholipid metabolism are significantly altered. Importantly, depletion of enzymes involved in phosphatidylserine metabolism as well as phosphatidylinositol biosynthesis reduce orthoflavivirus titers and cytopathic effects while inhibition of fatty acid monounsaturation only rescues from virus-induced cell death. Interestingly, interfering with ceramide synthesis has opposing effects on virus replication and cytotoxicity depending on the targeted enzyme. Thus, lipid remodeling by orthoflaviviruses includes distinct changes but also common patterns shared by several viruses that are needed for efficient infection and replication.

"My children will grow up more healthy than me because of the vaccinations they received": Using the migrant health trajectory model to understand Vietnamese American parents' attitudes towards vaccinations and the U.S. healthcare system.

Previous studies have examined the rationales affluent white American parents give for distrusting vaccinations and the U.S. healthcare system; fewer studies have investigated the vaccine- and healthcare-related attitudes of foreign-born parents who have resettled in the U.S. Drawing on 40 in-depth interviews with Vietnamese American parents who emigrated from Vietnam and reside in Southern California, this study finds that these parents favor vaccinations and trust the U.S. healthcare system. However, contrary to the "good" refugee and "model" minority stereotypes, which racializes Asian Americans as blindly adhering to authority to assimilate, these Vietnamese Americans reported purposefully agreeing to vaccinations because they believe that vaccines are a privileged prevention strategy, ensured by the U.S. healthcare system to safeguard their and their children's livelihoods. Interview participants chronicled their social experiences as refugees, particularly their upbringing in Vietnam (where they witnessed vaccine and healthcare inequities) and their emigration to and resettlement in the U.S. (a social setting they believe has an abundance of advantageous health resources) as social factors influencing their vaccination and healthcare standpoints. By attending to Vietnamese American parents' unique emigration health trajectories, this study highlights how vaccination and healthcare attitudes are social acts shaped by interlinking socio-historical, -political, and -cultural contexts.

Research, Science Identity, and Intent to Pursue a Science Career: A BUILD Intervention Evaluation at CSULB.

This paper presents an analysis of survey data to examine the association between participating in one of the National Institute of Health's (NIH) funded Building Infrastructure Leading to Diversity Initiative (BUILD) program and students' intent to pursue a career in science. Data were collected from students at California State University Long Beach (CSULB) to examine the effectiveness of the BUILD Scholars program. Both BUILD Scholars and non-BUILD students were surveyed. Propensity score matching was used to generate the non-BUILD comparison group. Multinomial logistic regression results revealed that students participating in the BUILD intervention were associated with significantly higher intent to pursue a career in science. Results also showed the importance of variables such as science identity and research participation when assessing interest in science careers. These findings have implications for STEM program evaluation and practice in higher education.

Advancing Inclusive Mentoring: An Effective Mentor Training Program Across Comprehensive and R2 Public Universities.

Positive and inclusive mentoring of undergraduate research students, particularly of students from historically underrepresented groups is critical. The Advancing Inclusive Mentoring (AIM) program was developed to share inclusive mentoring practices with mentors at undergraduate-focused campuses and was assessed across five minority-serving universities. Self-ratings of mentorship skill as very- and exceptionally developed increased by 58% after AIM completion, and 93% of participants indicated they were likely to change their mentoring following AIM. While 93% of mentors rated the AIM program as beneficial, and 88% found most or all six modules pertinent to their mentoring, campus variations existed in perceived benefit (87%-100%) and pertinence (80-97%). These results suggest that AIM is effective training for mentors of undergraduate researchers, including those from historically underrepresented groups.

Inter-visit and inter-reader reproducibility of multi-parametric diffusion-weighted MR imaging in longitudinally imaged patients with metabolic dysfunction-associated fatty liver disease and healthy volunteers.

BACKGROUND: Despite the widespread use of diffusion-weighted imaging (DWI) in metabolic dysfunction-associated fatty liver disease (MAFLD), MRI acquisition and quantification techniques vary in the literature suggesting the need for established and reproducible protocols. The goal of this study was to assess inter-visit and inter-reader reproducibility of DWI- and IVIM-derived parameters in patients with MAFLD and healthy volunteers using extensive sampling of the "fast" compartment, non-rigid registration, and exclusion voxels with poor fit quality. METHODS: From June 2019 to April 2023, 31 subjects (20 patients with biopsy-proven MAFLD and 11 healthy volunteers) were included in this IRB-approved study. Subjects underwent MRI examinations twice within 40 days. 3.0 T DWI was acquired using a respiratory-triggered spin-echo diffusion-weighted echo-planar imaging sequence (b-values of 0, 10, 20, 30, 40, 50, 100, 200, 400, 800 s/mm2). DWI series were co-registered prior to voxel-wise non-linear regression of the IVIM model and voxels with poor fit quality were excluded (normalized root mean squared error ≥ 0.05). IVIM parameters (perfusion fraction, f; diffusion coefficient, D; and pseudo-diffusion coefficient, D*), and apparent diffusion coefficients (ADC) were computed from manual segmentation of the right liver lobe performed by two analysts on two MRI examinations. RESULTS: All results are reported for f, D, D*, and ADC respectively. For inter-reader agreement on the first visit, ICC were of 0.985, 0.994, 0.986, and 0.993 respectively. For intra-reader agreement of analyst 1 assessed on both imaging examinations, ICC between visits were of 0.805, 0.759, 0.511, and 0.850 respectively. For inter-reader agreement on the first visit, mean bias and 95 % limits of agreement were (0.00 ± 0.03), (-0.01 ± 0.03) × 10-3 mm2/s, (0.70 ± 10.40) × 10-3 mm2/s, and (-0.02 ± 0.04) × 10-3 mm2/s respectively. For intra-reader agreement of analyst 1, mean bias and 95 % limits of agreement were (0.01 ± 0.09) × 10-3 mm2/s, (-0.01 ± 0.21) × 10-3 mm2/s, (-13.37 ± 56.19) × 10-3 mm2/s, and (-0.01 ± 0.16) × 10-3 mm2/s respectively. Except for parameter D* that was associated with between-subjects parameter variability (P = 0.009), there was no significant variability between subjects, examinations, or readers. CONCLUSION: With our approach, IVIM parameters f, D, D*, and ADC provided excellent inter-reader agreement and good to very good inter-visit or intra-reader agreement, thus showing the reproducibility of IVIM-DWI of the liver in MAFLD patients and volunteers.

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.

CAR/CETARS/CSAR Practice Guideline on Imaging the Adult Patient With Right Lower Quadrant Pain.

In 2023, the Canadian Society of Abdominal Radiology (CSAR) and Canadian Emergency, Trauma, and Acute Care Radiology Society (CETARS) received Canadian Association of Radiologists (CAR) member feedback that there was an unmet educational need for guidance in the imaging investigation of right lower quadrant (RLQ) pain. Members requested specific guidance on how to handle controversial scenarios including which test to order when, specifics of imaging protocols, and managing pregnant patients who have RLQ pain-all from a Canadian perspective. After conducting an exhaustive literature review, the working group agreed that a Canadian-specific set of guidelines was warranted. The management recommendations presented in this guideline were discussed as a group to achieve expert consensus. As the workup for RLQ pain can vary considerably in the paediatric population, the scope of this paper was restricted to adults (18 years of age or older). Whenever possible, the best evidence was used to inform the clinical guidance, and where gaps existed, the guidelines reflect consensus among experts in the field. The result is a framework to aid in this process of managing patients with RLQ pain across various clinical scenarios while addressing current questions and controversies, particularly those most relevant to the Canadian healthcare system.

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.

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.

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.

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.