Development and Evaluation of a Multisource Approach to Extend Mortality Follow-Up for Older Adults With Advanced Cancer Enrolled in Randomized Trials.

PURPOSE: Mortality data can complement primary end points from cancer clinical trials. Yet, identifying deaths after trial completion is challenging, as timely and comprehensive vital status data are unavailable in the United States. We developed and evaluated a multisource approach to capture death data after clinical trial completion. METHODS: Individuals age 70 years and older with incurable solid tumors or lymphoma and ≥1 aging-related condition were enrolled from October 2014 to March 2019 (ClinicalTrials.gov identifier: NCT02107443 and NCT02054741). Participants provided consent to link trial information to external sources. We developed a stepped approach for extended death capture using (1) active trial follow-up up to 1 year, (2) linkage to the National Death Index (NDI), and (3) obituary searches, thus generating a 5-year survival curve. In a random sample of 50 participants who died during trial follow-up, we estimated sensitivity of death data using NDI and obituary sources and computed survival times by data source. RESULTS: The two trials enrolled 1,169 participants; mean age was 76 years; 46% were female; and gastrointestinal cancer (30%) and lung cancer (26%) were the most common cancer types. Across data sources, maximum follow-up was >7 years; 5-year survival was 18%. In total, there were 841 deaths: 603 identified during trial follow-up; 199 from the NDI; and 39 from obituary searches. The sensitivity for death capture was 92% for the NDI and 94% for the obituary searches compared with the trial data, and computed survival times were similar across data sources. CONCLUSION: Extending clinical trial mortality follow-up through linkage with external data sources was feasible and accurate. Future cancer clinical trials should collect necessary consent and patient identifiers for vital status linkages that can enhance understanding of longer-term outcomes.

Feature-selective responses in macaque visual cortex follow eye movements during natural vision.

In natural vision, primates actively move their eyes several times per second via saccades. It remains unclear whether, during this active looking, visual neurons exhibit classical retinotopic properties, anticipate gaze shifts or mirror the stable quality of perception, especially in complex natural scenes. Here, we let 13 monkeys freely view thousands of natural images across 4.6 million fixations, recorded 883 h of neuronal responses in six areas spanning primary visual to anterior inferior temporal cortex and analyzed spatial, temporal and featural selectivity in these responses. Face neurons tracked their receptive field contents, indicated by category-selective responses. Self-consistency analysis showed that general feature-selective responses also followed eye movements and remained gaze-dependent over seconds of viewing the same image. Computational models of feature-selective responses located retinotopic receptive fields during free viewing. We found limited evidence for feature-selective predictive remapping and no viewing-history integration. Thus, ventral visual neurons represent the world in a predominantly eye-centered reference frame during natural vision.

Structure-guided engineering of biased-agonism in the human niacin receptor via single amino acid substitution.

The Hydroxycarboxylic acid receptor 2 (HCA2), also known as the niacin receptor or GPR109A, is a prototypical GPCR that plays a central role in the inhibition of lipolytic and atherogenic activities. Its activation also results in vasodilation that is linked to the side-effect of flushing associated with dyslipidemia drugs such as niacin. GPR109A continues to be a target for developing potential therapeutics in dyslipidemia with minimized flushing response. Here, we present cryo-EM structures of the GPR109A in complex with dyslipidemia drugs, niacin or acipimox, non-flushing agonists, MK6892 or GSK256073, and recently approved psoriasis drug, monomethyl fumarate (MMF). These structures elucidate the binding mechanism of agonists, molecular basis of receptor activation, and insights into biased signaling elicited by some of the agonists. The structural framework also allows us to engineer receptor mutants that exhibit G-protein signaling bias, and therefore, our study may help in structure-guided drug discovery efforts targeting this receptor.

Polyacrylonitrile as a versatile matrix for gold nanoparticle-based SERS substrates.

As an effective and ultrasensitive molecule detection technique, surface-enhanced Raman spectroscopy (SERS) needs efficient and highly responsive substrates to further enhance its sensitivity and utility. In this work, the preparation and characterisation of polyacrylonitrile/gold nanoparticle (PAN/AuNPs) composite porous films have been described for SERS-based detection of methylene blue (MB) dye. The PAN/AuNPs composite films were prepared with a simple dip coating technique, yielding a highly porous structure with uniformly dispersed Au nanoparticles (AuNPs). Scanning electron microscopy (SEM) revealed a linked pore network within the films. In X-ray diffraction (XRD), the characteristic crystal peak of AuNP clusters was observed, proving the presence of AuNPs in the composite. UV-vis absorption spectra also indicated the existence of the AuNPs. The methylene blue (MB) dye has been detected using PAN/AuNPs composite SERS substrates. These substrates showed excellent sensitivity by detecting 50 nM dye concentration and enhancing the Raman peak intensity at 1622 cm-1. The SERS enhancement factor (EF) for MB detection was determined to be around 106, demonstrating the remarkable sensitivity of the PAN/AuNPs composite porous films. The findings demonstrate the enormous potential of PAN/AuNPs composite porous films as reliable SERS substrates, displaying their efficacy in detecting trace levels of analytes in chemical and biological sensing applications.

Impact of in-hospital statin use on mortality in COVID-19 patients from a majority African American population.

BACKGROUND: The COVID-19 pandemic has claimed over 6.4 million lives globally. Finding effective medications to reduce mortality in hospitalized COVID-19 patients remains critical. No previous study has been published on the effects of statin use in a majority African American COVID-19 patient population. OBJECTIVE: This study aims to assess the relationship between in-hospital statin use and mortality in this population. METHODS: A retrospective chart review of patients diagnosed with COVID-19 from March 2020 to June 2020 admitted to the Phoebe Putney Health System in Albany, Georgia, an early epicenter of the COVID-19 pandemic, was conducted. The outcomes of 735 hospitalized COVID-19 positive patients from over 40 counties in Georgia were analyzed. The primary outcome of interest was all-cause mortality, with secondary outcomes of interest of ICU care, length of ICU stay, need for mechanical ventilator, duration of intubation, and need for dialysis. Multivariate logistic regression and Cox proportional hazards analysis were conducted to examine the effect of in-hospital statin use and mortality. RESULTS: 186 of 735 total patients were prescribed statins in-hospital. 83.8% were African American. Multivariate logistic regression found in-hospital statin use was not significantly associated with the primary outcome - all-cause mortality (p=0.23). Similar findings were seen in need for ICU care, length of ICU stay, need for mechanical ventilator, duration of intubation, and need for dialysis (p>0.05). Additionally, results from a Cox proportional hazards model found in-hospital statin use was not associated with survival time. Sensitivity analysis conducted on only African American patients validated that in-hospital statin use was not associated with all-cause mortality in these patients. Of note, immunosuppression and severe disease presentation were associated with a six-fold increase in risk of mortality and the largest decreases in survival time. CONCLUSION: It is possible statins have no mortality benefit for this patient population, but further research beyond this association study would need to be conducted to determine this conclusively. From this study, the best clinical recommendation would be to continue statins for COVID-19 patients with pre-hospital statin use and to launch a randomized clinical trial to definitively determine the efficacy of statins in the treatment of hospitalized COVID-19 patients.

When the whole is only the parts: non-holistic object parts predominate face-cell responses to illusory faces.

Humans are inclined to perceive faces in everyday objects with a face-like configuration. This illusion, known as face pareidolia, is often attributed to a specialized network of 'face cells' in primates. We found that face cells in macaque inferotemporal cortex responded selectively to pareidolia images, but this selectivity did not require a holistic, face-like configuration, nor did it encode human faceness ratings. Instead, it was driven mostly by isolated object parts that are perceived as eyes only within a face-like context. These object parts lack usual characteristics of primate eyes, pointing to the role of lower-level features. Our results suggest that face-cell responses are dominated by local, generic features, unlike primate visual perception, which requires holistic information. These findings caution against interpreting neural activity through the lens of human perception. Doing so could impose human perceptual biases, like seeing faces where none exist, onto our understanding of neural activity.

No Evidence for Cross-Modal fMRI Adaptation in Macaque Parieto-Premotor Mirror Neuron Regions.

To probe the presence of mirror neurons in the human brain, cross-modal fMRI adaptation has been suggested as a suitable technique. The rationale behind this suggestion is that this technique allows making more accurate inferences about neural response properties underlying fMRI voxel activations, beyond merely showing shared voxels that are active during both action observation and execution. However, the validity of using cross-modal fMRI adaptation to demonstrate the presence of mirror neurons in parietal and premotor brain regions has been questioned given the inconsistent and weak results obtained in human studies. A better understanding of cross-modal fMRI adaptation effects in the macaque brain is required as the rationale for using this approach is based on several assumptions related to macaque mirror neuron response properties that still need validation. Here, we conducted a cross-modal fMRI adaptation study in macaque monkeys, using the same action execution and action observation tasks that successfully yielded mirror neuron region cross-modal action decoding in a previous monkey MVPA study. We scanned two male rhesus monkeys while they first executed a sequence of either reach-and-grasp or reach-and-touch hand actions and then observed a video of a human actor performing these motor acts. Both whole-brain and region-of-interest analyses failed to demonstrate cross-modal fMRI adaptation effects in parietal and premotor mirror neuron regions. Our results, in line with previous findings in non-human primates, show that cross-modal motor-to-visual fMRI adaptation is not easily detected in monkey brain regions known to house mirror neurons. Thus, our results advocate caution in using cross-modal fMRI adaptation as a method to infer whether mirror neurons can be found in the primate brain.

Correction: Ab initio study of the electronic states of V3Si in momentum space.

[This corrects the article DOI: 10.1039/D3RA04535H.].

Cancer survivorship challenges of rural older adults: a qualitative study.

BACKGROUND: Although research has advanced the field of oncologic geriatrics with survivors to assess their cancer-related needs and devise patient-centered interventions, most of that research has excluded rural populations. This study aimed to understand the survivorship challenges and recommendations in the perspective of rural older adults. METHODS: This was a qualitative study that explored the survivorship challenges and recommendations of rural older adults who have completed curative intent chemotherapy for a solid tumor malignancy in the 12 months prior to enrollment in the present study. RESULTS: Twenty-seven older adult survivors from rural areas completed open-ended semi-structured interviews. The mean age was 73.4 (SD = 5.0). Most participants were non-Hispanic White (96.3%), female (59.3%), married (63.0%), and had up to a high school education (51.9%). Rural older survivors reported a general lack of awareness of survivorship care plans, communication challenges with healthcare team, transportation challenges, financial toxicity, psychological challenges, and diet and physical challenges. Rural older survivors recommend the provision of nutritional advice referral to exercise programs, and social support groups and for their healthcare providers to discuss their survivorship plan with them. CONCLUSIONS: Although study participants reported similar survivorship challenges as urban older adult survivors, additional challenges reported regarding transportation and consideration of farm animals have not been previously reported. Heightened awareness of the survivorship needs of rural older adults may result in better survivorship care for this population.

Ab initio study of the electronic states of V3Si in momentum space.

The electronic properties of V3Si are reported using the full-potential linearized augmented plane wave method. The electronic properties in the momentum space such as one and two dimensional electron momentum densities and the Fermi surface are presented. The momentum densities are compared with available experimental data. The one-dimensional electron momentum density i.e. the Compton profile is found to be in excellent agreement with the experiment. Anisotropy in the directional Compton profile corroborates the crystalline effects. The dimensions of the Fermi-surfaces are well captured by the 2D electron momentum density. The chemical bonding in this metallic compound is studied by means of the electron localization function and reciprocal form factor which suggest dominance of metallic bonding.

A multifunctional recyclable adsorbent based on engineered MIL-125 (Ti) magnetic mesoporous composite for the effective removal of pathogens.

The elimination of pathogenic bacteria from water sources is currently crucial for obtaining drinkable water. Therefore, the development of platforms with the ability to interact with pathogens and remove them is a potential future tool for medicine, food and water safety. In this work, we have grafted a layer of NH2-MIL-125 (Ti) on Fe3O4@SiO2 magnetic nanospheres for the removal of multiple pathogenic bacteria from water. The synthesized Fe3O4@SiO2@NH2-MIL-125 (Ti) nano adsorbent was characterized by FE-SEM, HR-TEM, FT-IR, XRD, BET surface analysis, magnetization tests, respectively, which illustrated its well-defined core-shell structure and magnetic behaviour. The prepared magnetic-MOF composite sorbent was attractive towards capturing a wide range of pathogens (S. typhimurium, S. aureus, E. coli, P. aeruginosa and K. pneumoniae) under experimental conditions. Influence factors such as adsorbent dosage, bacterial concentration, pH and incubation time were optimized for enhanced bacterial capture. The application of an external magnetic field removed Fe3O4@SiO2@NH2-MIL-125 (Ti) nano adsorbent from the solution along with sweeping the attached pathogenic bacteria. The non-specific removal efficiency of S. typhimurium for magnetic MOF composite was 96.58%, while it was only 46.81% with Fe3O4@SiO2 particles. For specific removal, 97.58% of S. typhimurium could be removed selectively from a mixture with monoclonal anti- Salmonella antibody conjugated magnetic MOF at a lower concentration of 1.0 mg/mL. The developed nano adsorbent may find great potential in microbiology applications and water remediation.

Genome-Transcriptome Transition Approaches to Characterize Anthocyanin Biosynthesis Pathway Genes in Blue, Black and Purple Wheat.

Colored wheat has gained enormous attention from the scientific community, but the information available on the anthocyanin biosynthetic genes is very minimal. The study involved their genome-wide identification, in silico characterization and differential expression analysis among purple, blue, black and white wheat lines. The recently released wheat genome mining putatively identified eight structural genes in the anthocyanin biosynthesis pathway with a total of 1194 isoforms. Genes showed distinct exon architecture, domain profile, regulatory elements, chromosome emplacement, tissue localization, phylogeny and synteny, indicative of their unique function. RNA sequencing of developing seeds from colored (black, blue and purple) and white wheats identified differential expressions in 97 isoforms. The F3H on group two chromosomes and F3'5'H on 1D chromosomes could be significant influencers in purple and blue color development, respectively. Apart from a role in anthocyanin biosynthesis, these putative structural genes also played an important role in light, drought, low temperature and other defense responses. The information can assist in targeted anthocyanin production in the wheat seed endosperm.

Effect of dietary anthocyanins on biomarkers of type 2 diabetes and related obesity: A systematic review and meta-analysis.

Anthocyanins have been reported for the protective effects against type 2 diabetes and related obesity. This meta-analysis examined the benefits of anthocyanins on type 2 diabetes and obesity biomarkers in animals and humans. The study included 21 clinical trials and 27 pre-clinical studies. A systematic search was conducted using the following inclusion criteria: in vivo rodent studies; human randomized clinical trials, both aimed at assessing the fasting blood glucose (FBG), HbA1c, total cholesterol, triglycerides, high-density lipoprotein and low-density lipoprotein; and study duration of at least two weeks. Out of the 201 examined publications, 48 were shortlisted after implementation of the selection criteria. Results of clinical trials demonstrated that consumption of anthocyanin-rich food significantly reduced the FBG (p < 0.0001), HbA1c (p = 0.02), TC (p = 0.010), TG (p = 0.003), LDL (p = 0.05) and increases the HDL (p = 0.03) levels. Similarly, pre-clinical studies demonstrated the amelioration of the HbA1c (p = 0.02), FBG, TC, TG, and LDL (p < 0.00001), with non-significant changes in the HDL (p = 0.11). Sub-group analysis indicated dose-dependent effect. This compilation confirms that consuming anthocyanin-rich foods positively correlates with the reduction in the blood glucose and lipid levels in diabetic and obese subjects.

New insights into APCVD grown monolayer MoS2 using time-domain terahertz spectroscopy.

In modern era, wireless communications at ultrafast speed are need of the hour and search for its solution through cutting edge sciences is a new perspective. To address this issue, the data rates in order of terabits per second (TBPS) could be a key step for the realization of emerging sixth generation (6G) networks utilizing terahertz (THz) frequency regime. In this context, new class of transition metal dichalcogenides (TMDs) have been introduced as potential candidates for future generation wireless THz technology. Herein, a strategy has been adopted to synthesize high-quality monolayer of molybdenum di-sulfide (MoS2) using indigenously developed atmospheric pressure chemical vapor deposition (APCVD) set-up. Further, the time-domain transmission and sheet conductivity were studied as well as a plausible mechanism of terahertz response for monolayer MoS2 has been proposed and compared with bulk MoS2. Hence, the obtained results set a stepping stone to employ the monolayer MoS2 as potential quantum materials benefitting the next generation terahertz communication devices.

Effect of anthocyanins on gut health markers, Firmicutes-Bacteroidetes ratio and short-chain fatty acids: a systematic review via meta-analysis.

Researchers discovered that diets rich in anthocyanin-rich fruits and vegetables significantly impacted gut flora. To conclude, large-scale randomized controlled clinical trials are challenging to conduct; therefore, merging data from multiple small studies may aid. A systematic review collects and analyses all research on a particular subject and design. This comprehensive review and meta-analysis examined the influence of dietary anthocyanins on Firmicutes/Bacteroide (Fir/Bac) and short-chain fatty acids (SCFAs) content. The current meta-analysis followed the guidelines of PRISMA-the preferred reporting items for systematic reviews and meta-analyses. Diets high in anthocyanins substantially reduced the Fir/Bac ratio in the assessed trials. Among three SCFAs, the highest impact was observed on acetic acid, followed by propionic acid, and then butanoic acid. The meta-analysis results also obtained sufficient heterogeneity, as indicated by I2 values. There is strong evidence that anthocyanin supplementation improves rodent gut health biomarkers (Fir/Bac and SCFAs), reducing obesity-induced gut dysbiosis, as revealed in this systematic review/meta-analysis. Anthocyanin intervention duration and dosage significantly influenced the Fir/Bac ratio and SCFA. Anthocyanin-rich diets were more effective when consumed over an extended period and at a high dosage.

Categorization learning induced changes in action representations in the macaque STS.

Neuroimaging and single cell recordings have demonstrated the presence of STS body category-selective regions (body patches) containing neurons responding to presentation of static bodies and body parts. To date, it remains unclear if these body patches and additional STS regions respond during observation of different categories of dynamic actions and to what extent categorization learning influences representations of observed actions in the STS. In the present study, we trained monkeys to discriminate videos depicting three different actions categories (grasping, touching and reaching) with a forced-choice action categorization task. Before and after categorization training, we performed fMRI recordings while monkeys passively observed the same action videos. At the behavioral level, after categorization training, monkeys generalized to untrained action exemplars, in particular for grasping actions. Before training, uni- and/or multivariate fMRI analyses suggest a broad representation of dynamic action categories in particular in posterior and middle STS. Univariate analysis further suggested action category specific training effects in middle and anterior body patches, face patch ML and posterior STS region MT and FST. Overall, our fMRI experiments suggest a widespread representation of observed dynamic bodily actions in the STS that can be modulated by visual learning, supporting its proposed role in action recognition.

Intrinsic functional clustering of the macaque insular cortex.

The functional organization of the primate insula has been studied using a variety of techniques focussing on regional differences in either architecture, connectivity, or function. These complementary methods offered insights into the complex organization of the insula and proposed distinct parcellation schemes at varying levels of detail and complexity. The advent of imaging techniques that allow non-invasive assessment of structural and functional connectivity, has popularized data-driven connectivity-based parcellation methods to investigate the organization of the human insula. Yet, it remains unclear if the subdivisions derived from these data-driven clustering methods reflect meaningful descriptions of the functional specialization of the insula. In this study, we employed hierarchical clustering to examine the cluster parcellations of the macaque insula. As our aim was exploratory, we examined parcellations consisting of two up to ten clusters. Three different cluster validation methods (fingerprinting, silhouette, elbow) converged on a four-cluster solution as the most optimal representation of our data. Examining functional response properties of these clusters, in addition to their brain-wide functional connectivity suggested a functional specialization related to processing gustatory, somato-motor, vestibular and social visual cues. However, a more detailed functional differentiation aligning with previous functional investigations of insula subfields became evident at higher cluster numbers beyond the proposed optimal four clusters. Overall, our findings demonstrate that resting-state-based hierarchical clustering can provide a meaningful description of the insula's functional organization at some level of detail. Nonetheless, cluster parcellations derived from this method are best combined with data obtained through other modalities, to provide a more comprehensive and detailed account of the insula's complex functional organization.

The Use of Cannabidiol in Patients With Low Back Pain Caused by Lumbar Spinal Stenosis: An Observational Study.

Background Spinal stenosis is a degenerative narrowing of the spinal canal with encroachment on the neural structures by surrounding bone and soft tissue. This chronic low back condition can cause restrictions in mobility, impairment of daily activities, opioid dependence, anxiety, depression, and reduced quality of life. Spinal stenosis can be treated through surgical and nonsurgical methods, but neither has proven consistently reliable. Cannabidiol (CBD) has also been observed to have anxiolytic, anti-inflammatory, antiemetic, and antipsychotic behaviors. CBD may provide greater nonsurgical treatment options for the pain associated with spinal stenosis while minimizing the need for opioids. An observational study was undertaken to assess the effects of CBD on patients suffering from chronic spinal stenosis. Methodology This observational study was investigator-initiated and designed to determine the effect of hemp-derived CBD gel caps for patients with spinal stenosis related to low back pain and leg pain relative to patient outcomes, medication utilization, and quality of life outcome measures. A total of six physician visits would be required where a set of surveys would be filled out each four weeks apart. Results The study population consisted of 48 patients. The patient population's age ranged from 63 to 95 years and was normally distributed, with a mean age of 75 ± 7.13 years. The sex distribution was 33% male and 67% female patients. The pain was broken down between the six visits for each of the following four questions: pain right now, usual pain level during the week, best pain level during the week, and worst pain level during the week. Usual pain levels (p < 0.001) and worst pain levels (p < 0.005) demonstrated statistically significant improvement over time, while pain right now (p > 0.05) and best pain level (p > 0.05) stayed consistent throughout without statistical significance. Conclusions This open-label, prospective, observational study found that treatment with hemp-derived CBD gel caps was associated with significant improvements in pain scores and several quality-of-life measures for patients with lumbar spinal stenosis.

Perspectives of Orthopedic Patients on Medical Cannabis: A Survey of More Than 2500 Patients.

Nationwide perspectives on cannabis have changed dramatically over recent decades. Although cannabis remains illegal at the federal level, medical cannabis (MC) is now legal in most states, and research has continued to show its effectiveness in a variety of medical conditions. However, both perception and acceptance of MC by the general public are evolving and remain poorly understood. Treating patients effectively with these novel therapeutics requires an understanding of the complex interplay of social and legal factors that could affect patient use. This cross-sectional survey study of more than 2500 patients sought to assess current patient perspectives on MC and to investigate factors related to its use that may represent barriers to broader patient use. Most respondents would consider using MC for chronic pain or other medical conditions. Most respondents were aware of the legal status of MC in their state, and 9 of 10 respondents believed that MC should be legal throughout the United States. General public knowledge of the utility of MC is an area needing improvement because older patients were significantly less likely to believe that MC is safe to use or that MC is safer than prescription opioids. As has been reported in previous literature, social stigma and cost appear to remain barriers for patient use of MC. Our findings provide further insight into current patient perspectives on MC, aiding both medical providers and researchers as we continue to provide access to and research MC. [Orthopedics. 2022;45(6):e309-e314.].

Integrated transcriptional and metabolomics signature pattern of pigmented wheat to insight the seed pigmentation and other associated features.

Anthocyanin biosynthesis in plants is complex, especially in a polyploid monocot wheat plant. Using whole-genome sequencing, transcriptomics, and LC-MS/MS, we investigated anthocyanin pigmentation patterns in (black, blue, and purple) colored wheat seeds. According to differential gene expression profiling, 2AS-MYC, 7DL-MYB, and WD40 regulatory genes control purple pericarp coloration, 4DL-MYC, 2AS-MYC, 7DL-MYB, WD40 control blue aleurone coloration, and 4DL-MYC, 7DL-MYB, WD40 controls black aleurone color. We hypothesized that at least one MYC and MYB isoform is sufficient to regulate the anthocyanin synthesis in pericarp or aleurone. Transcriptomics and metabolomics revealed that the purple pericarp trait is associated with acylated anthocyanins compared to blue aleurone. Based upon the reduced expressions of the genes belonging to the 4D, SSR molecular marker mapping, variant calling using genome sequencing, and IGV browser gene structure visualization, it was inferred that the advanced black and blue wheat lines were substitution lines (4E{4D}), with very small recombinations. Pericarp anthocyanin pigmentation is controlled by a mutation in chromosome 2AS of purple wheat, and environmental variations influence pigmented pericarp trait. The expression patterns of anthocyanin structural and other genes varied in different colored wheat, corroborating differences in agronomical metrics. Ovate seed shape trait in black and blue wheat dragged with 4E chromosome.