Enhanced SARS-CoV-2 entry via UPR-dependent AMPK-related kinase NUAK2.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) remodels the endoplasmic reticulum (ER) to form replication organelles, leading to ER stress and unfolded protein response (UPR). However, the role of specific UPR pathways in infection remains unclear. Here, we found that SARS-CoV-2 infection causes marginal activation of signaling sensor IRE1α leading to its phosphorylation, clustering in the form of dense ER-membrane rearrangements with embedded membrane openings, and XBP1 splicing. By investigating the factors regulated by IRE1α-XBP1 during SARS-CoV-2 infection, we identified stress-activated kinase NUAK2 as a novel host-dependency factor for SARS-CoV-2, HCoV-229E, and MERS-CoV entry. Reducing NUAK2 abundance or kinase activity impaired SARS-CoV-2 particle binding and internalization by decreasing cell surface levels of viral receptors and viral trafficking likely by modulating the actin cytoskeleton. IRE1α-dependent NUAK2 levels were elevated in SARS-CoV-2-infected and bystander non-infected cells, promoting viral spread by maintaining ACE2 cell surface levels and facilitating virion binding to bystander cells.

Falls prechemotherapy and toxicity-related hospitalization during adjuvant chemotherapy for breast cancer in older women: Results from the prospective multicenter HOPE trial.

BACKGROUND: Older women with breast cancer frequently experience toxicity-related hospitalizations during adjuvant chemotherapy. Although the geriatric assessment can identify those at risk, its use in clinic remains limited. One simple, low-cost marker of vulnerability in older persons is fall history. Here, the authors examined whether falls prechemotherapy can identify older women at risk for toxicity-related hospitalization during adjuvant chemotherapy for breast cancer. METHODS: In a prospective study of women >65 years old with stage I-III breast cancer treated with adjuvant chemotherapy, the authors assessed baseline falls in the past 6 months as a categorical variable: no fall, one fall, and more than one fall. The primary end point was incident hospitalization during chemotherapy attributable to toxicity. Multivariable logistic regression was used to examine the association between falls and toxicity-related hospitalization, adjusting for sociodemographic, disease, and geriatric covariates. RESULTS: Of the 497 participants, 60 (12.1%) reported falling before chemotherapy, and 114 (22.9%) had one or more toxicity-related hospitalizations. After adjusting for sociodemographic, disease, and geriatric characteristics, women who fell more than once within 6 months before chemotherapy had greater odds of being hospitalized from toxicity during chemotherapy compared to women who did not fall (50.0% vs. 20.8% experienced toxicity-related hospitalization, odds ratio, 4.38; 95% confidence interval, 1.66-11.54, p = .003). CONCLUSIONS: In this cohort of older women with early breast cancer, women who experienced more than one fall before chemotherapy had an over 4-fold increased risk of toxicity-related hospitalization during chemotherapy, independent of sociodemographic, disease, and geriatric factors.

Outcome prioritization and preferences among older adults with cancer starting chemotherapy in a randomized clinical trial.

INTRODUCTION: Older adults with cancer facing competing treatments must prioritize between various outcomes. This study assessed health outcome prioritization among older adults with cancer starting chemotherapy. METHODS: Secondary analysis of a randomized trial addressing vulnerabilities in older adults with cancer. Patients completed three validated outcome prioritization tools: 1) Health Outcomes Tool: prioritizes outcomes (survival, independence, symptoms) using a visual analog scale; 2) Now vs. Later Tool: rates the importance of quality of life at three times-today versus 1 or 5 years in the future; and 3) Attitude Scale: rates agreement with outcome-related statements. The authors measured the proportion of patients prioritizing various outcomes and evaluated their characteristics. RESULTS: A total of 219 patients (median [range] age 71 [65-88], 68% with metastatic disease) were included. On the Health Outcomes Tool, 60.7% prioritized survival over other outcomes. Having localized disease was associated with choosing survival as top priority. On the Now vs. Later Tool, 50% gave equal importance to current versus future quality of life. On the Attitude Scale, 53.4% disagreed with the statement "the most important thing to me is living as long as I can, no matter what my quality of life is"; and 82.2% agreed with the statement "it is more important to me to maintain my thinking ability than to live as long as possible". CONCLUSION: Although survival was the top priority for most participants, some older individuals with cancer prioritize other outcomes, such as cognition and function. Clinicians should elicit patient-defined priorities and include them in decision-making.

How Hot Electron Generation at the Solid-Liquid Interface Is Different from the Solid-Gas Interface.

Excitation of hot electrons by energy dissipation under exothermic chemical reactions on metal catalyst surfaces occurs at both solid-gas and solid-liquid interfaces. Despite extensive studies, a comparative operando study directly comparing electronic excitation by electronically nonadiabatic interactions at solid-gas and solid-liquid interfaces has not been reported. Herein, on the basis of our in situ techniques for monitoring energy dissipation as a chemicurrent using a Pt/n-Si nanodiode sensor, we observed the generation of hot electrons in both gas and liquid phases during H2O2 decomposition. As a result of comparing the current signal and oxygen evolution rate in the two phases, surprisingly, the efficiency of reaction-induced excitation of hot electrons increased by ∼100 times at the solid-liquid interface compared to the solid-gas interface. The boost of hot electron excitation in the liquid phase is due to the presence of an ionic layer lowering the potential barrier at the junction for transferring hot electrons.

Cell-Penetrating Peptide-Bismuth Bicycles.

Cell-penetrating peptides (CPPs) play a significant role in the delivery of cargos into human cells. We report the first CPPs based on peptide-bismuth bicycles, which can be readily obtained from commercially available peptide precursors, making them accessible for a wide range of applications. These CPPs enter human cells as demonstrated by live-cell confocal microscopy using fluorescently labelled peptides. We report efficient sequences that demonstrate increased cellular uptake compared to conventional CPPs like the TAT peptide (derived from the transactivating transcriptional activator of human immunodeficiency virus 1) or octaarginine (R8 ), despite requiring only three positive charges. Bicyclization triggered by the presence of bismuth(III) increases cellular uptake by more than one order of magnitude. Through the analysis of cell lysates using inductive coupled plasma mass spectrometry (ICP-MS), we have introduced an alternative approach to examine the cellular uptake of CPPs. This has allowed us to confirm the presence of bismuth in cells after exposure to our CPPs. Mechanistic studies indicated an energy-dependent endocytic cellular uptake sensitive to inhibition by rottlerin, most likely involving macropinocytosis.

Live-virus serum neutralization after bivalent SARS-CoV-2 mRNA vaccination in hemodialysis patients.

The development of bivalent booster vaccines addresses the ongoing evolution of the emerging B.1.1.529 (omicron) variant subtypes that are known to escape vaccine-induced neutralizing antibody response. Little is known about the immunogenicity and reactogenicity of bivalent mRNA vaccines in hemodialysis patients with impaired vaccine response. In this prospective, observational cohort study, we analyzed SARS-CoV-2 anti-S1 IgG, surrogate neutralizing antibodies (SNA), and live-virus neutralization against the SARS-CoV-2 wildtype and the BA.5 variant in 42 hemodialysis patients with and without prior SARS-CoV-2 infection before and after an additional fifth bivalent vaccine dose. Anti-S1 IgG and SNA were significantly higher in hemodialysis patients with prior infection than in patients without infection (p < 0.001 and p < 0.01, respectively). In patients without prior infection, both antibody levels increased, and live-virus neutralizing antibodies against the wildtype and the BA.5 variant were correspondingly significantly higher after bivalent booster vaccination (p < 0.001 for both). Conversely, in patients with prior infection, anti-S1 IgG and SNA did not alter significantly, and bivalent booster vaccination did not induce additional humoral immune response against the SARS-CoV-2 wildtype and the BA.5 variant. Thus, bivalent mRNA vaccines might increase humoral responses in hemodialysis patients without prior infection. Larger clinical trials are needed to help guide vaccination strategies in these immunocompromised individuals.

Live-virus neutralization of the omicron variant in children and adults 14 months after SARS-CoV-2 wild-type infection.

Data on cross-neutralization of the SARS-CoV-2 omicron variant more than 1 year after SARS-CoV-2 infection are urgently needed, especially in children, to predict the likelihood of reinfection and to guide vaccination strategies. In a prospective observational cohort study, we evaluated live-virus neutralization of the SARS-CoV-2 omicron (BA.1) variant in children compared with adults 14 months after mild or asymptomatic wild-type SARS-CoV-2 infection. We also evaluated immunity to reinfection conferred by previous infection plus COVID-19 mRNA vaccination. We studied 36 adults and 34 children 14 months after acute SARS-CoV-2 infection. While 94% of unvaccinated adults (16/17) and children (32/34) neutralized the delta (B.1.617.2) variant, only 1/17 (5.9%) unvaccinated adults, 0/16 (0%) adolescents and 5/18 (27.8%) children <12 years of age had neutralizing activity against omicron (BA.1). In convalescent adults, one or two doses of mRNA vaccine increased delta and omicron neutralization 32-fold, similar to a third mRNA vaccination in uninfected adults. Neutralization of omicron was 8-fold lower than that of delta in both groups. In conclusion, our data indicate that humoral immunity induced by previous SARS-CoV-2 wild-type infection more than 1 year ago is insufficient to neutralize the current immune escape omicron variant.

Neutralizing antibody response against the B.1.617.2 (delta) and the B.1.1.529 (omicron) variants after a third mRNA SARS-CoV-2 vaccine dose in kidney transplant recipients.

Seroconversion after COVID-19 vaccination is impaired in kidney transplant recipients. Emerging variants of concern such as the B.1.617.2 (delta) and the B.1.1.529 (omicron) variants pose an increasing threat to these patients. In this observational cohort study, we measured anti-S1 IgG, surrogate neutralizing, and anti-receptor-binding domain antibodies three weeks after a third mRNA vaccine dose in 49 kidney transplant recipients and compared results to 25 age-matched healthy controls. In addition, vaccine-induced neutralization of SARS-CoV-2 wild-type, the B.1.617.2 (delta), and the B.1.1.529 (omicron) variants was assessed using a live-virus assay. After a third vaccine dose, anti-S1 IgG, surrogate neutralizing, and anti-receptor-binding domain antibodies were significantly lower in kidney transplant recipients compared to healthy controls. Only 29/49 (59%) sera of kidney transplant recipients contained neutralizing antibodies against the SARS-CoV-2 wild-type or the B.1.617.2 (delta) variant and neutralization titers were significantly reduced compared to healthy controls (p < 0.001). Vaccine-induced cross-neutralization of the B.1.1.529 (omicron) variants was detectable in 15/35 (43%) kidney transplant recipients with seropositivity for anti-S1 IgG, surrogate neutralizing, and/or anti-RBD antibodies. Neutralization of the B.1.1.529 (omicron) variants was significantly reduced compared to neutralization of SARS-CoV-2 wild-type or the B.1.617.2 (delta) variant for both, kidney transplant recipients and healthy controls (p < .001 for all).

SARS-CoV-2 infection remodels the host protein thermal stability landscape.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global threat to human health and has compromised economic stability. In addition to the development of an effective vaccine, it is imperative to understand how SARS-CoV-2 hijacks host cellular machineries on a system-wide scale so that potential host-directed therapies can be developed. In situ proteome-wide abundance and thermal stability measurements using thermal proteome profiling (TPP) can inform on global changes in protein activity. Here we adapted TPP to high biosafety conditions amenable to SARS-CoV-2 handling. We discovered pronounced temporal alterations in host protein thermostability during infection, which converged on cellular processes including cell cycle, microtubule and RNA splicing regulation. Pharmacological inhibition of host proteins displaying altered thermal stability or abundance during infection suppressed SARS-CoV-2 replication. Overall, this work serves as a framework for expanding TPP workflows to globally important human pathogens that require high biosafety containment and provides deeper resolution into the molecular changes induced by SARS-CoV-2 infection.

Patient-Defined Goals and Preferences Among Adults With Advanced Neuroendocrine Tumors.

BACKGROUND: Patient preferences (quantity vs quality of life; present vs future health) have not been investigated in patients with neuroendocrine tumors (NETs). The goal of this cross-sectional study was to evaluate patient values toward treatment goals and competing health outcomes among adults with NETs. PATIENTS AND METHODS: Patients with well-differentiated, grade 1 or 2, advanced NETs starting a new systemic therapy completed 4 tools: (1) Health Outcomes Tool, which ranks the importance of 4 outcomes (survival, function/independence, freedom from pain, freedom from symptoms); (2) Attitude Scale, which identifies the extent to which patients agree with statements related to health outcomes; (3) Now versus Later Tool, which ranks the relative importance of quality of life (QoL) now versus 1 and 5 years from now; and (4) Prognosis and Treatment Perceptions Questionnaire, which identifies the amount of information the patient prefers to receive about their disease and treatment, the patient's treatment goal, the patient's perception of the physician's treatment goal, and self-reported health status. RESULTS: We recruited 60 patients with NETs (50.0% aged ≥65 years; 96.7% with stage IV disease). Primary tumor locations included the gastrointestinal tract (41.7%), pancreas (30.0%), and lung (21.7%). A plurality of patients reported maintaining independence as their most important health outcome (46.7%), followed by survival (30.0%), freedom from pain (11.7%), and freedom from symptoms (11.7%). A total of 67% of patients agreed with the statement, "I would rather live a shorter life than lose my ability to take care of myself"; 85.0% agreed with the statement, "It is more important to me to maintain my thinking ability than to live as long as possible." When asked to choose between current QoL versus QoL 1 year or 5 years in the future as more important, 48.3% and 40.0% of patients valued their QoL 1 year and 5 years in the future, respectively, more than their current QoL. Only 51.7% of patients believed their physician's treatment goals aligned with their own. CONCLUSIONS: Adult patients with NETs strongly value independence over survival. More communication between patients with NETs and their physicians is needed to ensure that patient preferences are incorporated into treatment plans.

Trioctylphosphine Oxide (TOPO)-Assisted Facile Fabrication of Phosphorus-Incorporated Nanostructured Carbon Nitride Toward Photoelectrochemical Water Splitting with Enhanced Activity.

Designing nanostructured arrays of two-dimensional surfaces and interfaces is a versatile approach to increasing their photoelectrochemical activity. Here, phosphorus (P)-incorporated nanostructured carbon nitride (h-PCN) with an enlarged surface area is fabricated by employing trioctylphosphine oxide (TOPO) as a dopant precursor for visible-light-driven photoelectrochemical water splitting to produce hydrogen. The structural, morphological, and electronic properties of the photocatalyst have been characterized through various physicochemical techniques. We show that the incorporation of P into the g-C3N4 framework enhances light absorption over broad regimes, charge separation, and migration, as well as the specific surface area, showing excellent photocurrent enhancement (5.4 folds) in the cathodic direction as compared to bulk g-C3N4. Moreover, the photocathode shows 3.3-fold enhancement in current at zero biased potential. Without using any cocatalyst, the photoelectrodes produced 27 µmol h-1 of H2 and 13 µmol h-1of O2 with 95% faradic efficiency. The excellent photoelectrochemical behavior toward water-splitting reactions by the photoelectrode is attributed to the synergistic effect of P incorporation and active sites emerging from the nanostructured architecture of the material. This work demonstrates the facile fabrication of nanostructured P-incorporated g-C3N4 toward water-splitting reactions to produce hydrogen without using a cocatalyst in a simple and cost-effective way.

Plasmonic hot carrier-driven photoelectrochemical water splitting on antenna-reactor Pt/Ag/TiO2 Schottky nanodiodes.

Plasmonic photoelectrochemical (PEC) water splitting has excited immense interest, as it can overcome the intrinsic limitations of semiconductors, in terms of light absorption, by the localized-surface plasmon resonances effect. Here, to get insight into the role of plasmonic hot carriers in plasmonic water splitting, a rational design of an antenna-reactor type Pt/Ag/TiO2 metal-semiconductor Schottky nanodiode was fabricated and used as a photoanode. Using the designed PEC cell system combined with the Pt/Ag/TiO2 nanodiode, we show that the plasmonic hot carriers excited from Ag were utilized for the oxygen (O2) evolution reaction and, consequently, had a decisive role in the enhancement of the photocatalytic efficiency. These results were supported by finite-difference time-domain simulations, and the faradaic efficiency was measured by the amount of actual gas produced. Therefore, this study provides a deep understanding of the dynamics and mechanisms of plasmonic hot carriers in plasmonic-assisted PEC water splitting.

Thiamyxins: Structure and Biosynthesis of Myxobacterial RNA-Virus Inhibitors.

During our search for novel myxobacterial natural products, we discovered the thiamyxins: thiazole- and thiazoline-rich non-ribosomal peptide-polyketide hybrids with potent antiviral activity. We isolated four congeners of this unprecedented natural product family with the non-cyclized thiamyxin D fused to a glycerol unit at the C-terminus. Alongside their structure elucidation, we present a concise biosynthesis model based on biosynthetic gene cluster analysis and isotopically labelled precursor feeding. We report incorporation of a 2-(hydroxymethyl)-4-methylpent-3-enoic acid moiety by a GCN5-related N-acetyltransferase-like decarboxylase domain featuring polyketide synthase. The thiamyxins show potent inhibition of RNA viruses in cell culture models of corona, zika and dengue virus infection. Their potency up to a half maximal inhibitory concentration of 560 nM combined with milder cytotoxic effects on human cell lines indicate the potential for further development of the thiamyxins.

Korean red ginseng suppresses 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced inflammation in the substantia nigra and colon.

Parkinson's disease (PD) is a neurodegenerative disease involving dopaminergic neuronal death in the substantia nigra (SN); recent studies have shown that interactions between gut and brain play a critical role in the pathogenesis of PD. In this study, the anti-inflammatory effect of Korean red ginseng (KRG) and the changes in gut microbiota were evaluated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. Male nine-week-old C57BL/6 mice were injected intraperitoneally with 30 mg/kg of MPTP at 24-h intervals for 5 days. Two hours after the daily MPTP injection, the mice were orally administered 100 mg/kg of KRG, which continued for 7 days beyond the MPTP injections, for a total of 12 consecutive days. Eight days after the final KRG administration, the pole and rotarod tests were performed and brain and colon samples of the mice were collected. Dopaminergic neuronal death, activation of microglia and astrocytes, α-synuclein and expressions of inflammatory cytokines and disruption of tight junction were evaluated. In addition, 16S ribosomal RNA gene sequencing of mouse fecal samples was performed to investigate microbiome changes. KRG treatment prevented MPTP-induced behavioral impairment, dopaminergic neuronal death, activation of microglia and astrocytes in the nigrostriatal pathway, disruption of tight junction and the increase in α-synuclein, interleukin-1ß and tumor necrosis factor-α expression in the colon. The 16S rRNA sequencing revealed that MPTP altered the number of bacterial species and their relative abundances, which were partially suppressed by KRG treatment. Especially, KRG suppressed the abundance of the inflammation-related phylum Verrucomicrobia and genera Ruminococcus and Akkermansia (especially Akkermansia muciniphila), and elevated the abundance of Eubacterium, which produces the anti-inflammatory substances. These findings suggest that KRG prevents MPTP-induced dopaminergic neuronal death, activation of microglia and astrocytes, and accumulation of α-synuclein in the SN, and the regulation of inflammation-related factors in the colon may influence the effect.

Associations between nutritional factors and chemotherapy toxicity in older adults with solid tumors.

BACKGROUND: Nutritional status can directly affect morbidity and mortality in older adults with cancer. This study evaluated the association between pretreatment body mass index (BMI), albumin level, and unintentional weight loss (UWL) in the prior 6 months and chemotherapy toxicity among older adults with solid tumors. METHODS: This was a secondary analysis of a prospective, multicenter study involving chemotherapy-treated patients 65 years old or older. Geriatric assessment, BMI, albumin level, and UWL data were collected before treatment. Multivariable logistic regression models evaluated the associations between nutritional factors and the risk of grade 3 or higher (grade 3+) chemotherapy toxicity. RESULTS: Seven hundred fifty patients with a median age of 72 years (range, 65-94 years) and mostly stage IV disease were enrolled. The median pretreatment BMI and albumin values were 26 kg/m2 (range, 15.1-52.1 kg/m2 ) and 3.9 mg/dL (range, 1.0-5.0 mg/dL), respectively. Nearly 50% of the patients reported UWL, with 17.6% reporting >10% UWL. Multivariable analysis revealed no association between >10% UWL and a risk for grade 3+ chemotherapy toxicity (adjusted odds ratio [AOR], 0.87; P = .58). Multivariable analysis showed a trend toward an association between a BMI ≥ 30 kg/m2 and a decreased risk of grade 3+ chemotherapy toxicity (AOR, 0.65; P = .06), whereas a low albumin level (≤3.6 mg/dL) was associated with a higher risk of grade 3+ chemotherapy toxicity (AOR, 1.50; P = .03). An analysis of the joint effect of BMI and albumin demonstrated the lowest risk of grade 3+ chemotherapy toxicity among patients with high BMIs (≥30 kg/m2 ) and normal albumin levels (AOR, 0.41; P = .008). CONCLUSIONS: Among older adults with solid tumors, higher BMIs and normal albumin levels are associated with a lower risk of grade 3+ chemotherapy toxicity. Additional research is warranted to define the clinical significance of nutritional markers and to inform future interventions.

Clinicopathologic risk factors of radioactive iodine therapy based on response assessment in patients with differentiated thyroid cancer: a multicenter retrospective cohort study.

PURPOSE: We investigated whether predictive clinicopathologic factors can be affected by different response criteria and how the clinical usefulness of radioactive iodine (RAI) therapy should be evaluated considering variable factors in patients with differentiated thyroid carcinoma (DTC). METHODS: A total of 1563 patients with DTC who underwent first RAI therapy after total or near total thyroidectomy were retrospectively enrolled from 25 hospitals. Response to therapy was evaluated with two different protocols based on combination of biochemical and imaging studies: (1) serum thyroglobulin (Tg) and neck ultrasonography (US) and (2) serum Tg, neck US, and radioiodine scan. The responses to therapy were classified into excellent and non-excellent or acceptable and non-acceptable to minimize the effect of non-specific imaging findings. We investigated which factors were associated with response to therapy depending on the follow-up protocols as well as response classifications. Multivariate logistic regression analysis was performed to identify factors significantly predicting response to therapy. RESULTS: The proportion of patients in the excellent response group significantly decreased from 76.5 to 59.6% when radioiodine scan was added to the follow-up protocol (P < 0.001). Preparation method (recombinant human TSH vs. thyroid hormone withdrawal) was a significant factor for excellent response prediction evaluated with radioiodine scan (OR 2.129; 95% CI 1.687-2.685; P < 0.001) but was not for other types of response classifications. Administered RAI activity, which was classified as low (1.11 GBq) or high (3.7 GBq or higher), significantly predicted both excellent and acceptable responses regardless of the follow-up protocol. CONCLUSIONS: The clinical impact of factors related to response prediction differed depending on the follow-up protocol or classification of response criteria. A high administered activity of RAI was a significant factor predicting a favorable response to therapy regardless of the follow-up protocol or classification of response criteria.

An easy method for the evaluation of visual tumor heterogeneity of 18F-FDG PET/CT using 10-step color scale: A correlative study in patients with lung cancer.

OBJECTIVE: The purpose of this study was to assess the correlation between visual assessment by the peritumoral halo layer (PHL) method and analysis with texture and intensity histogram metrics for evaluating tumor heterogeneity (TH) in fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) of patients with lung cancer. SUBJECTS AND METHODS: We retrospectively reviewed the 64 patients with records of 18F-FDG PET/CT prior to treatment. After tumor segmentation by the PHL method, three visual patterns: the existence of cold defect, the location of hottest core, and number of irregular layers can be obtained on 18F-FDG PET/CT images. To examine the correlation, first-order entropy was extracted by texture analysis and the area under curve-cumulative SUV-volume histogram (AUC-CSH) value was used in the intensity histogram analysis. A correlation between the visual assessment and the parameters of the metrics analysis was evaluated. We also evaluated the inter-correlation among the visual assessment and correlation between metabolic tumor volume (MTV) and parameters of TH. RESULTS: A significant correlation was noted between visual assessment and quantitative indices of texture and intensity histogram analysis with high inter-observer agreement. Additionally, a significant inter-correlation between the existence of cold defect, location of hottest core, and the number of irregular layers was observed. Metabolic tumor volume was correlated with all of the parameters in the 18F-FDG PET/CT images, such as AUC-CSH, entropy, existence of cold defect, location of hottest core, and number of irregular layers. CONCLUSION: In this study, we provide a new visual assessment criterion of TH with a strong inter-observer agreement. The visual analysis using the PHL method could be a potential marker for evaluating heterogeneous tumors.

Comparison of self-report and electronic monitoring of 6MP intake in childhood ALL: a Children's Oncology Group study.

Adequate exposure to oral 6-mercaptopurine (6MP) during maintenance therapy for childhood acute lymphoblastic leukemia (ALL) is critical for sustaining durable remissions; accuracy of self-reported 6MP intake is unknown. We aimed to directly compare self-report to electronic monitoring (Medication Event Monitoring System [MEMS]) and identify predictors of overreporting in a cohort of 416 children with ALL in first remission over 4 study months (1344 patient-months for the cohort) during maintenance therapy. Patients were classified as "perfect reporters" (self-report agreed with MEMS), "overreporters" (self-report was higher than MEMS by ≥5 days/month for ≥50% of study months), and "others" (not meeting criteria for perfect reporter or overreporter). Multivariable logistic regression examined sociodemographic and clinical characteristics, 6MP dose intensity, TPMT genotype, thioguanine nucleotide levels, and 6MP nonadherence (MEMS-based adherence <95%) associated with the overreporter phenotype; generalized estimating equations compared 6MP intake by self-report and MEMS. Self-reported 6MP intake exceeded MEMS at least some of the time in 84% of patients. Fifty patients (12%) were classified as perfect reporters, 98 (23.6%) as overreporters, 2 (0.5%) as underreporters, and 266 (63.9%) as others. In multivariable analysis, the following variables were associated with the overreporter phenotype: non-white race: Hispanic, odds ratio (OR), 2.4, P = .02; Asian, OR, 3.1, P = .02; African American, P < .001; paternal education less than college (OR, 1.4, P = .05); and 6MP nonadherence (OR, 9.4, P < .001). Self-report of 6MP intake in childhood ALL overestimates true intake, particularly in nonadherent patients, and should be used with caution.

Prediction of future weight change with dopamine transporter in patients with Parkinson's disease.

Fluctuating body weight is a commonly reported nonmotor feature in patients with Parkinson's disease (PD). We hypothesised that striatal dopamine transporter (DAT) density at the time of diagnosis might play an important role in weight regulation in patients with PD. DAT density was measured from 123I-FP-CIT single-photon emission computed tomography. Region-of-interest analyses were performed to measure the specific binding of 123I-FP-CIT to DAT, and the putamen-to-caudate nucleus ratio (PCR) was calculated. Body weight was measured at baseline (W0) and at 48 months (W48). We classified subjects into three groups: weight loss, stable, and weight gain. In final analyses, 163 patients (106 men, 57 women) were included. PCR significantly differed by group in men, but not in women or across all patients. In men, PCR was slightly negatively associated with the percentage change in weight. No such correlation was found across all patients or in women. In univariate and multivariate logistic regression analyses, low PCR was associated with future weight gain in men with PD but not in women. In conclusion, striatal DAT availability at the time of diagnosis could predict subsequent weight change in men with PD.

Association between patient-reported hearing and visual impairments and functional, psychological, and cognitive status among older adults with cancer.

BACKGROUND: Hearing and visual impairments are common among community-dwelling older adults, and are associated with psychological, functional, and cognitive deficits. However, to the authors' knowledge, little is known regarding their prevalence among older patients with cancer. METHODS: The current study was a secondary analysis combining 2 prospective cohorts of adults aged ≥65 years with solid tumors who were receiving chemotherapy. The authors assessed the association between patient-reported hearing and/or visual impairment (defined as fair/poor grading by self-report) and physical function, instrumental activities of daily living (IADLs), anxiety, depression, and cognition. Descriptive analyses were conducted to summarize patient and treatment characteristics. One-way analysis of variance and chi-square tests were conducted as appropriate to examine differences between patients with and without sensory impairments. Logistic regression was used to analyze associations between sensory impairments and outcomes. RESULTS: Among 750 patients with a median age of 72 years who had solid tumors (29% with breast/gynecological tumors, 28% with lung tumors, and 27% with gastrointestinal tumors), approximately 18% reported hearing impairment alone, 11% reported visual impairment alone, and 7% reported dual sensory impairment. Hearing impairment was associated with IADL dependence (odds ratio [OR], 1.9), depression (OR, 1.6), and anxiety (OR, 1.6). Visual impairment was associated with IADL dependence (OR, 1.9), poor physical function (OR, 1.9), and depression (OR, 2.5). Dual impairment was associated with IADL dependence (OR, 2.8), anxiety (OR, 2.3), depression (OR, 2.5), and cognitive impairment (OR, 3.2). CONCLUSIONS: Sensory impairment is common among older adults with cancer. Patients with sensory impairment are more likely to have functional, psychological, and cognitive deficits. Interventions aimed at improving the vision and hearing of older adults with cancer should be studied. Cancer 2018. © 2018 American Cancer Society.