Individual Sites Research Articles

The 2022 NCI Community Oncology Research Program (NCORP) Landscape Committee Assessment: Methods and participating practice group characteristics.

e13517 Background: The National Cancer Institute Community Oncology Research Program (NCORP) Landscape Assessment (funding support from 2UG1CA189824) provides important information about available services and capacity to engage in research among the 46 NCORP sites (encompassing ~1000 discrete clinics). We describe the methods for conducting the Landscape Assessment and present practice group characteristics. Methods: The Landscape Committee included representation from all NCORP research bases and community NCORP site members. The 2022 assessment was updated from the 2017 assessment after a network-wide request for questions. All items were reviewed for relevance, question quality, applicability to community sites, and data collection burden. The 2022 assessment update included an expanded range of topics (e.g., social determinants of health screening, pediatric and AYA services, fertility preservation services). After an initial pilot phase, the final assessment was distributed to NCORP affiliate/sub-affiliates via representatives designated by the participating sites. Data were collected April-June, 2022. Results: 271 NCORP practice groups rostered and provided demographics for 517 individual sites (98% response from NCORP sites; 52% of discrete clinics). 70 practice groups (26%) represented multiple NCORP clinics, with a median of 4 clinics (IQR: 2-7 sites). Practice groups were located in the Midwest (42%), South (30%), West (18%) and Northeast (10%). Treatment was provided to adults only at 83% of groups, 12% treated adults and children, and 5% provided only pediatric care. 28% were independently owned and 64% were owned by large regional health systems; 28% participated in the Center for Medicare and Medicaid Services Oncology Care Model. Cancer treatment services were provided in the hospital setting for 73%, freestanding practices in 49%, and 64% at inpatient clinics. The median number of annual cancer cases was 875 (IQR: 453-2,004). Practice groups reported on average most new patients were White (79%), followed by Black (13%), Asian (2.5%), and Native Hawaiian/Pacific Islander (0.64%). 10% were identified as Hispanic ethnicity. Provider availability to recruit patients for research varied by provider type (95% medical oncology; 73% radiation oncology; 47% general surgery/surgical oncology; 38% gynecology oncology; 21% uro-oncology; 19% neuro-oncology; 15% pediatric oncology; & 7% orthopedic surgical oncology). Conclusions: The Landscape assessment was successfully updated and administered in 2022 with a high response rate. Results provide updated information about community site infrastructure and capacity to conduct research among NCORP clinics. Detailed results are available to investigators by request for concept development and to help identify affiliate/sub-affiliate sites to participate in studies.

SARS-CoV-2 Detection and Culture in Different Biological Specimens from Immunocompetent and Immunosuppressed COVID-19 Patients Infected with Two Different Viral Strains.

Introduction-The dynamics of SARS-CoV-2 shedding and replication in humans remain incompletely understood. Methods-We analyzed SARS-CoV-2 shedding from multiple sites in individuals with an acute COVID-19 infection by weekly sampling for five weeks in 98 immunocompetent and 25 immunosuppressed individuals. Samples and culture supernatants were tested via RT-PCR for SARS-CoV-2 to determine viral clearance rates and in vitro replication. Results-A total of 2447 clinical specimens were evaluated, including 557 nasopharyngeal swabs, 527 saliva samples, 464 urine specimens, 437 anal swabs and 462 blood samples. The SARS-CoV-2 genome sequences at each site were classified as belonging to the B.1.128 (ancestral strain) or Gamma lineage. SARS-CoV-2 detection was highest in nasopharyngeal swabs regardless of the virus strain involved or the immune status of infected individuals. The duration of viral shedding varied between clinical specimens and individual patients. Prolonged shedding of potentially infectious virus varied from 10 days up to 191 days, and primarily occurred in immunosuppressed individuals. Virus was isolated in culture from 18 nasal swab or saliva samples collected 10 or more days after onset of disease. Conclusions-Our findings indicate that persistent SARS-CoV-2 shedding may occur in both competent or immunosuppressed individuals, at multiple clinical sites and in a minority of subjects is capable of in vitro replication.

The Coral Bleaching Automated Stress System (CBASS): A low‐cost, portable system for standardized empirical assessments of coral thermal limits

AbstractOcean warming is increasingly affecting marine ecosystems across the globe. Reef‐building corals are particularly affected by warming, with mass bleaching events increasing in frequency and leading to widespread coral mortality. Yet, some corals can resist or recover from bleaching better than others. Such variability in thermal resilience could be critical to reef persistence; however, the scientific community lacks standardized diagnostic approaches to rapidly and comparatively assess coral thermal vulnerability prior to bleaching events. We present the Coral Bleaching Automated Stress System (CBASS) as a low‐cost, open‐source, field‐portable experimental system for rapid empirical assessment of coral thermal thresholds using standardized temperature stress profiles and diagnostics. The CBASS consists of four or eight flow‐through experimental aquaria with independent water masses, lighting, and individual automated temperature controls capable of delivering custom modulating thermal profiles. The CBASS is used to conduct daily thermal stress exposures that typically include 3‐h temperature ramps to multiple target temperatures, a 3‐h hold period at the target temperatures, and a 1‐h ramp back down to ambient temperature, followed by an overnight recovery period. This mimics shallow water temperature profiles observed in coral reefs and prompts a rapid acute heat stress response that can serve as a diagnostic tool to identify putative thermotolerant corals for in‐depth assessments of adaptation mechanisms, targeted conservation, and possible use in restoration efforts. The CBASS is deployable within hours and can assay up to 40 coral fragments/aquaria/day, enabling high‐throughput, rapid determination of thermal thresholds for individual genotypes, populations, species, and sites using a standardized experimental framework.

Biogeochemical cycling of chromium and chromium isotopes in the sub-tropical North Atlantic Ocean

Chromium (Cr) is a redox-sensitive element and because Cr isotopes are fractionated by redox and/or biological processes, the Cr isotopic composition of ancient marine sediments may be used to infer changes in past seawater oxygenation or biological productivity. While there appears to be a ‘global correlation’ between the dissolved Cr concentration and Cr isotopic composition of seawater, there is ongoing debate about the relative importance of external sources and internal cycling on shaping the distribution of dissolved Cr that needs to be resolved to validate the efficacy of using Cr isotopes as a paleo proxy. Here, we present full water column depth profiles of total dissolved Cr (Cr(VI)+Cr(III)) and dissolved Cr isotopes (δ53Cr), together with ancillary data, for three stations along a transect (GEOTRACES GApr08) across the sub-tropical North Atlantic. Concentrations of dissolved Cr ranged between 1.84 and 2.63 nmol kg-1, and δ53Cr values varied from 1.06 to 1.42‰. Although atmospheric dust, hydrothermal vents and seabed sediments have the potential to modify the distribution of Cr in the oceans, based on our observations, there is no clear evidence for substantial input of Cr from these sources in our study region although benthic inputs of Cr may be locally important in the vicinity of hydrothermal vents. Subsurface waters (below the surface mixed layer to 700 m water depth) were very slightly depleted in Cr (by up to ~0.4 nmol kg-1), and very slightly enriched in heavy Cr isotopes (by up to ~0.14‰), relative to deeper waters and the lowest Cr concentrations and highest δ53Cr values coincided with lowest concentrations of colloidal (0.02 to 0.2 μm size fraction) Fe. We found no direct evidence for biological uptake of dissolved Cr in the oligotrophic euphotic zone or removal of Cr in modestly oxygen depleted waters (O2 concentrations ~130 μmol kg-1). Rather, we suggest removal of Cr (probably in the form of Cr(III)) in subsurface waters is associated with the formation of colloid aggregates of Fe-(oxyhydr)oxides. This process is likely enhanced by the high lithogenic particle load in this region, and represents a previously unrecognized export flux of Cr. Regeneration of Cr in deeper waters leads to subtly increased levels of Cr alongside decreased δ53Cr values at individual sites, but this trend is more obvious at the global scale, with δ53Cr values decreasing with increasing radiocarbon age of deep waters, from 1.16 ± 0.10‰ (1SD, n=11) in deep Atlantic waters to 0.77 ± 0.10‰ (1SD, n=25) in deep Pacific waters. Removal of relatively isotopically light Cr from subsurface waters onto particulate material and regeneration of this Cr back into the dissolved phase in deep waters partly accounts for the systematic relationship between δ53Cr and Cr concentrations in seawater discussed by other studies.

Selective events at individual sites underlie the evolution ofmonkeypox virus clades.

In endemic regions (West Africa and the Congo Basin), the genetic diversity of monkeypox virus (MPXV) is geographically structured into two major clades (Clades I and II) that differ in virulence and host associations. Clade IIb is closely related to the B.1 lineage, which is dominating a worldwide outbreak initiated in 2022. Lineage B.1 has however accumulated mutations of unknown significance that most likely result from apolipoprotein B mRNA editing catalytic polypeptide-like 3 (APOBEC3) editing. We applied a population genetics-phylogenetics approach to investigate the evolution of MPXV during historical viral spread in Africa and to infer the distribution of fitness effects. We observed a high preponderance of codons evolving under strong purifying selection, particularly in viral genes involved in morphogenesis and replication or transcription. However, signals of positive selection were also detected and were enriched in genes involved in immunomodulation and/or virulence. In particular, several genes showing evidence of positive selection were found to hijack different steps of the cellular pathway that senses cytosolic DNA. Also, a few selected sites in genes that are not directly involved in immunomodulation are suggestive of antibody escape or other immune-mediated pressures. Because orthopoxvirus host range is primarily determined by the interaction with the host immune system, we suggest that the positive selection signals represent signatures of host adaptation and contribute to the different virulence of Clade I and II MPXVs. We also used the calculated selection coefficients to infer the effects of mutations that define the predominant human MPXV1 (hMPXV1) lineage B.1, as well as the changes that have been accumulating during the worldwide outbreak. Results indicated that a proportion of deleterious mutations were purged from the predominant outbreak lineage, whose spread was not driven by the presence of beneficial changes. Polymorphic mutations with a predicted beneficial effect on fitness are few and have a low frequency. It remains to be determined whether they have any significance for ongoing virus evolution.

The differential effects of upadacitinib treatment on skin rashes of four anatomical sites in patients with atopic dermatitis

BackgroundUpadacitinib is an oral Janus kinase (JAK) 1 inhibitor approved in Japan for moderate-to-severe atopic dermatitis (AD), and it provides a high therapeutic efficacy.ObjectivesWe compared the therapeutic effects of upadacitinib on skin rashes of individual anatomical sites, head and neck, upper limbs, lower limbs, and trunk in patients with AD.MethodsFrom August 2021 to December 2022, 65 Japanese patients with moderate-to-severe AD (aged ≥ 12 years) were treated with oral once daily upadacitinib 15 mg plus twice daily topical corticosteroids of moderate-to-strongest classes.ResultsThe eczema area and severity indexes (EASIs) of individual sites decreased significantly at weeks 4, 12, and 24 compared to those at week 0 in parallel to total (whole body) EASI. The achievement rates of EASI 75 at week 24 and of EASI 90 at week 12 of lower limbs were significantly higher than those of trunk. The percent reductions of EASI of lower limbs at weeks 12 and 24 were significantly higher than those of head and neck and of trunk.ConclusionsAmong the four anatomical sites, the treatment responsiveness to upadacitinib in lower limbs appeared the highest, while those in trunk and in head and neck appeared relatively lower.

Developing OCHROdb, a comprehensive quality checked database of open chromatin regions from sequencing data

International consortia, including ENCODE, Roadmap Epigenomics, Genomics of Gene Regulation and Blueprint Epigenome have made large-scale datasets of open chromatin regions publicly available. While these datasets are extremely useful for studying mechanisms of gene regulation in disease and cell development, they only identify open chromatin regions in individual samples. A uniform comparison of accessibility of the same regulatory sites across multiple samples is necessary to correlate open chromatin accessibility and expression of target genes across matched cell types. Additionally, although replicate samples are available for majority of cell types, a comprehensive replication-based quality checking of individual regulatory sites is still lacking. We have integrated 828 DNase-I hypersensitive sequencing samples, which we have uniformly processed and then clustered their regulatory regions across all samples. We checked the quality of open-chromatin regions using our replication test. This has resulted in a comprehensive, quality-checked database of Open CHROmatin (OCHROdb) regions for 194 unique human cell types and cell lines which can serve as a reference for gene regulatory studies involving open chromatin. We have made this resource publicly available: users can download the whole database, or query it for their genomic regions of interest and visualize the results in an interactive genome browser.

Epigenetic Analysis of the Dopamine Transporter Gene DAT1 with a Focus on Personality Traits in Athletes.

Human phenotypes (traits) are determined by the selective use of a person's unique genotype (DNA sequence), following exposure to environmental stimuli, such as exercise. Inducing profound changes in epigenetics may be an underlying factor of the beneficial effects of exercise. This study aimed to investigate the association between methylation in the promoter region of the DAT1 gene and personality traits measured by the NEO-FFI questionnaire in a group of athletes. The study group included 163 athletes, and the control group consisted of 232 non-athletes. The obtained results show several significant differences between the studied groups of subjects. The Extraversion scale and the Conscientiousness scale results of the NEO-FFI are significantly higher in the group of athletes compared to controls. The total methylation and the number of methylated islands in the promoter region of the DAT1 gene are higher in the study group. Pearson's linear correlation between the total methylation, the number of methylated islands and the NEO-FFI shows significant results for the Extraversion and Agreeability scales. The total methylation and the number of methylated islands in the promoter region of the DAT1 gene are higher in the study group. Pearson's linear correlation between the total methylation, the number of methylated islands and the NEO-FFI shows significant results for the Extraversion and Agreeability scales. Our analysis of the methylation status of individual CpG sites revealed a new direction of research into the biological aspects of regulating dopamine release and personality traits in people practicing sports.

Strategic Management of Inclusive Schools (Multi Site Study at SDN Gadang 2 and SDN Benua Anyar 8 Banjarmasin)

This study aims to describe the strategic management applied by inclusive schools in achieving their goals. Observed in depth in 3 research focuses; (1) Strategic management formulation, (2) Strategic Management Implementation, (3) Strategic Management Evaluation at Elementary School Gadang 2 and Elementary School Benua Anyar 8 Banjarmasin. The research was carried out with a descriptive qualitative approach. The data sources are headmasters, inclusion managers, special assistant teachers, class teachers and supervisors who are determined using purposive sampling techniques combined with snowball sampling techniques during research. Data collection is obtained by interview research methods and observations which are also included in documentation. Then the data is analyzed in individual site analysis and cross-site analysis. The results of this study show that strategic management in inclusive elementary schools has been carried out, although the utilization of the results of the SWOT analysis has not been carried out optimally, both schools have a good opportunity to improve schools. The strategic management implemented by Elementary School Gadang 2 and Elementary School Benua Anyar 8 Banjarmasin includes (1) formulation of strategic management, there is the formulation of vision and mision, analysis of the internal & external environment to the formulation of goals and objectives and determination of programs; (2) The implementation of strategic management can be seen from the teaching and learning process, with the use of curriculum 13, resource empowerment, fulfilment of infrastructure, to building social networks, cooperation and communication to realize program implementation; (3) Strategic management evaluation, including evaluation of programs that have been implemented and evaluation of teacher performance carried out by the headmaster through supervision with various techniques

Implementation of a sample design for a survey of program participants using time-location sampling.

To assess the feeding practices and behaviors of women and young children participating in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC), USDA currently funds the longitudinal WIC Infant and Toddler Feeding Practices Study-2 (WIC ITFPS-2). In 2013, the study used time-location sampling (TLS) to enroll a cohort of infants who participated in WIC around birth. The children are subsequently followed across their first six years of life, regardless of their participation in WIC, with an additional follow-up at age nine years. A woman may enroll her child in WIC either during pregnancy or postpartum. For this study, a representative sample of infants enrolled in WIC was desired. Because the associations between WIC prenatal support and education and feeding practices and behaviors are substantively important to this study, the sample needed to include both women enrolling their children prenatally and women enrolling their children postnatally. For prenatal WIC enrollees, we attempted to complete a prenatal interview with the mother prior to the child's birth. This paper describes the TLS approach used and the challenges addressed in implementation of the sample design and selection for the WIC ITFPS-2. Our approach generated a probability sample (subject to site geographic and size exclusions) using a stratified, multistage design, but there were challenges at each stage of selection. First, a WIC site was selected, and then newly enrolled WIC participants were sampled within selected sites during predetermined recruitment windows based on the site's average flow of new WIC enrollees. We discuss issues faced, including overcoming incomplete lists of individual WIC sites and discrepancies between projected new WIC enrollment counts and actual flow of new WIC enrollments during the recruitment period.

Provisioning ecotourism does not increase tiger shark site fidelity

A perennial criticism of provisioning ecotourism is that it alters the natural behavior and ecology of the target species by providing an artificial food source. Here we evaluate its impact on the long-term site fidelity patterns of tiger sharks in French Polynesia. We hypothesized that a significant impact of provisioning would lead to (1) increases in individual site fidelity over time, and (2) an increase in the number of resident individuals over time. Of 53 individuals photo-identified and monitored during > 500 dives over five years, 10 individuals accounted for > 75% of all sightings, whereas 35 sharks were sighted very infrequently. Even the most frequently observed tiger sharks exhibited overall low fidelity at the site and showed no increase in site fidelity over time. Furthermore, the number of tiger sharks sighted during each dive did not increase. The observed patterns of tiger shark sightings were best explained by natural movements, including general roaming within home ranges along the coastline and seasonal migrations. Despite the apparent lack of impact of provisioning ecotourism on tiger shark ecology in Tahitian waters, it would be prudent to implement a strict code of conduct during any future provisioning activities to maximize the safety of participants and animals involved.

Measuring basin-scale aquifer storage change and mapping specific yield in Albuquerque, New Mexico, USA, with repeat microgravity data

Study RegionThe groundwater basin underlying the City of Albuquerque, New Mexico, USA. Study FocusThe study focuses on changes in groundwater storage and how those changes relate to groundwater-level changes. Groundwater storage change was measured using repeat microgravity at 35 stations from 2016 to 2021. Usually, storage is monitored by converting groundwater-level changes to storage changes using the aquifer storage coefficient, a difficult property to measure. With gravity, storage change can be measured directly. The storage coefficient, or specific yield in an unconfined aquifer, was estimated using the gravity method at individual sites, and a map created showing how this property varies over the region. New Hydrological Insights for the RegionFor the first time, a map of specific yield was produced based on interpolated maps of gravity-derived storage change and groundwater-level change, allowing inference of this property over a broad region even without collocated monitoring wells and gravity stations. Gravity data indicate aquifer drawdown and recovery mainly occurs in the central part of the basin where pumping is greatest. This spatial distribution is not captured by the more widely spaced monitoring well network. Because the aquifer is recovering from historically greater-magnitude pumping, net-neutral storage change (inflow=outflow) occurs when pumping from the central part of the well field is about 1.54 × 107 cubic meters (12,500 acre-feet) per year.

Artificial rockpools: Seaweed colonisation and productivity vary between sites but are consistent across environmental contexts

Artificial structures are widespread features of coastal environments, but are poor surrogates of natural rocky shores because they generally support depauperate assemblages with reduced population sizes. This has generated significant interest in eco-engineering solutions, including retrofitting seawalls with artificial rockpools to increase water retention and provide microhabitats. Although these have proven effective at individual sites, widespread uptake is contingent on evidence of consistent benefits across a range of contexts. In this study, Vertipools™ were retrofitted on eight seawalls in different environmental contexts (urban v rural and estuarine v marine) along the Irish Sea coastline and were monitored regularly for two years. Seaweed colonisation proceeded in a manner similar to patterns described for natural and artificial intertidal systems in general, consisting of early dominance by ephemeral species followed by the appearance and eventual establishment of perennial habitat-formers. After 24 months, species richness did not differ between contexts, but differed between sites. The units supported populations of large habitat-forming seaweeds at all sites. Productivity and community respiration of the colonising communities differed between sites by up to 0.5 mg O2 L−1 min−1, but not across environmental contexts. This study demonstrates that bolt-on rockpools attract similar levels of biotic colonisation and functioning in a variety of temperate environmental contexts, and could be considered for widespread implementation as an eco-engineering solution.

Pitting fails to sustain increases in ecosystem structure in arid rangelands

Mechanized approaches to the rehabilitation of degraded rangeland have been extremely popular since the early 1930s but their effectiveness depends on climatic and environmental conditions (e.g. soil texture, pre‐treatment plant cover). We evaluated the effects of pitting, a popular rehabilitation technique based on the creation of elongated soil depressions (pits), on ecosystem structure from 14 trials conducted at 10 sites across an extensive area (~100,000 km2) of rangelands in eastern Australia. Averaged across all sites and rehabilitation times, pitting had a significant positive effect on the cover of perennial forbs and annuals, and suppressed bare ground compared with untreated sites. However, these treatment effects varied with different site conditions such as soil texture, and pre‐treatment rainfall and plant cover among individual sites. Pre‐treatment plant cover, and rainfall in the 3 months prior to measurements increased the effects of pitting on litter cover, and time since treatment increased the relative effect of pitting on annual plant cover. Negative effect of pitting on the cover of bare soil declined with increasing rainfall. Soil moisture was generally greater beneath pits than either control soils or soils between the pits (inter‐pits). Despite some positive effects on annual plant and litter cover, pitting effects were generally short lived, suggesting that a single pitting treatment may fail to achieve long‐term rehabilitation. Given that these field trials were conducted half a century ago under conditions of higher average rainfall, the prognosis for the success of pitting under current conditions of lower rainfall and higher temperature is generally poor.

Evaluation of diversity indices to estimate clonal dominance in gene therapy studies

In cell and gene therapy, achieving the stable engraftment of an abundant and highly polyclonal population of gene-corrected cells is one of the key factors to ensure the successful and safe treatment of patients. Because integrative vectors have been associated with possible risks of insertional mutagenesis leading to clonal dominance, monitoring the relative abundance of individual vector insertion sites in patients' blood cells has become an important safety assessment, particularly in hematopoietic stem cell-based therapies. Clinical studies often express clonal diversity using various metrics. One of the most commonly used is the Shannon index of entropy. However, this index aggregates two distinct aspects of diversity, the number of unique species and their relative abundance. This property hampers the comparison of samples with different richness. This prompted us to reanalyze published datasets and to model the properties of various indices as applied to the evaluation of clonal diversity in gene therapy. A normalized version of the Shannon index, such as Pielou's index, or Simpson's probability index is robust and useful to compare sample evenness between patients and trials. Clinically meaningful standard values for clonal diversity are herein proposed to facilitate the use of vector insertion site analyses in genomic medicine practice.

Analysis of bi-atrial function using CMR feature tracking and long-axis shortening approaches in patients with diastolic dysfunction and atrial fibrillation.

Atrial function can be assessed using advancing cardiovascular magnetic resonance (CMR) post-processing methods: atrial feature tracking (FT) strain analysis or a long-axis shortening (LAS) technique. This study aimed to first compare the two FT and LAS techniques in healthy individuals and cardiovascular patients and then investigated how left (LA) and right atrial (RA) measurements are related to the severity of diastolic dysfunction or atrial fibrillation. Sixty healthy controls and 90 cardiovascular disease patients with coronary artery disease, heart failure, or atrial fibrillation, underwent CMR. LA and RA were analyzed for standard volumetry as well as for myocardial deformation using FT and LAS for the different functional phases (reservoir, conduit, booster). Additionally, ventricular shortening and valve excursion measurements were assessed with the LAS module. The measurements for each of the LA and RA phases were correlated (p < 0.05) between the two approaches, with the highest correlation coefficients occurring in the reservoir phase (LA: r = 0.83, p < 0.01, RA: r = 0.66, p < 0.01). Both methods demonstrated reduced LA (FT: 26 ± 13% vs 48 ± 12%, LAS: 25 ± 11% vs 42 ± 8%, p < 0.01) and RA reservoir function (FT: 28 ± 15% vs 42 ± 15%, LAS: 27 ± 12% vs 42 ± 10%, p < 0.01) in patients compared to controls. Atrial LAS and FT decreased with diastolic dysfunction and atrial fibrillation. This mirrored ventricular dysfunction measurements. Similar results were generated for bi-atrial function measurements between two CMR post-processing approaches of FT and LAS. Moreover, these methods allowed for the assessment of incremental deterioration of LA and RA function with increasing left ventricular diastolic dysfunction and atrial fibrillation. A CMR-based analysis of bi-atrial strain or shortening discriminates patients with early-stage diastolic dysfunction prior to the presence of compromised atrial and ventricular ejection fractions that occur with late-stage diastolic dysfunction and atrial fibrillation. • Assessing right and left atrial function with CMR feature tracking or long-axis shortening techniques yields similar measurements and could potentially be used interchangeably based on the software capabilities of individual sites. • Atrial deformation and/or long-axis shortening allow for early detection of subtle atrial myopathy in diastolic dysfunction, even when atrial enlargement is not yet apparent. • Using a CMR-based analysis to understand the individual atrial-ventricular interaction in addition to tissue characteristics allows for a comprehensive interrogation of all four heart chambers. In patients, this could add clinically meaningful information and potentially allow for optimal therapies to be chosen to better target the dysfunction.

Using 17 years of beach/dune profile monitoring to characterize morphological dynamics related to significant extreme water level events in North Brittany (France)

Long-term in situ monitoring of beach morphology is crucial for understanding the physical processes of coastal changes and defining the strategies of sustainable coastal management. Monthly surveys based on the beach/dune profile measurements started in July 2004 along six transects distributed along the Vougot beach (North Brittany). The analysis of these data from 2004 to 2021 shows that the eastern part of the beach has experienced chronic erosion during the 17-year period. This erosion has led to a lowering of the beach profile by about −1 to −1.5 m, and has resulted in the removal of beach sand such that waves now impact the underlying Holocene peat and Pleistocene silts or pebbles during most of the year. Conversely, the western part of the beach has accreted. Vougot beach is thus experiencing a rotation phenomenon characterized by a longshore sediment flux from the east to the west. The multidecadal evolution of the beach/dune system is punctuated by events causing significant retreat of the dune, especially when storm waves are combined with high spring tide levels. The event causing the most significant morphological changes was associated with extreme water levels (EWL) up to 9.6 m (i.e., Anne storm in February 2014), causing 14.5 m3 l.m−1 of dune sediment loss. The analysis of 17 years of hydrodynamic conditions (waves and water levels) indicates an increase in the wave runup height (+65 %) and EWL (+17 %). Calculation of the water level that exceeds the dune toe position (Δzexceedance) helps to further quantify the impacts of storm events on dune volume changes. The Anne storm had an EWL with a return period of approximately 13 years, but when combined with the dune toe position, showed the largest dune toe exceedance value (3.0 m), corresponding to a return period of approximately 21 years. Lastly, the events causing the most significant dune erosion during this 17-year study period have also caused shoreline erosion and/or landward barrier migration at many other sites in North Brittany, showing the broader scale impacts of observations at individual study sites.

A Spin-Dependent Model for Multi-Heme Bacterial Nanowires.

The electrical properties of conductive heme-based nanowires found in Geobacter sulfurreducens bacteria were investigated using spin-dependent density functional theory (DFT). Molecular orbitals were generated using a restricted open-shell model which was solved by applying constraints to the spin-separated unrestricted open-shell model. Charge transport was simulated at different length scales ranging from individual heme sites up to the monomer unit of the nanowire, looking at hopping and tunneling between neighboring heme porphyrins with different Fe oxidation states. The resulting spin-dependent DFT results indicate that tunneling rates between heme sites are highly dependent on oxidation state and transport pathway modeled. The model demonstrates the importance of spin dependence for electron hopping, oxidation state, and decoherence transport in cytochromes. Applying non-equilibrium's Green's function to the system confirmed a substantial decrease in decoherent charge transport for the oxidized molecule at lower Fermi energies. In addition, partial or full oxidation of the heme sites in the nanowire created conditions for spin-dependent transport that can be exploited for spin-filtering effects in nanodevices.

In vivo detection of healthy skin: Comparison of multiphoton microscopy and reflectance confocal microscopy.

Noninvasive skin examination evolved rapidly in recent years, with multiphoton microscopy (MPM) and reflectance confocal microscopy (RCM) being used to image in-vivo skin at high resolution. The aim of this study is to compare the imaging clarity between the two techniques and measure the thickness of the epidermis in different body sites. We also measured the degree of skin aging with noninvasive tools. Fifty-six volunteers were evaluated and measured at three different body sites, including the cheek, volar forearm, and back. We used RCM and MPM to evaluate the clarity of each skin layer, including stratum corneum, stratum granulosum, stratum spinosum, dermo-epidermal junction, and dermis. We measured epidermal thickness (ET) at the three body sites in individuals of different ages and genders. We assessed skin aging by the second harmonic to autofluorescence aging index of dermis (SAAID), and multiple linear regression was used to analyze the factors affecting SAAID. MPM had advantages in observation of stratum granulosum, collagen fiber, and elastic fiber (p<0.001), but RCM provided better observation in dermo-epidermal junction layer (p<0.001). The epidermis was thicker in the cheek area than the volar forearm and back in both RCM and MPM detection, and the average ET measured by MPM was lower than RCM. ET varied among the three body sites with significant differences (p<0.05). ET was significantly lower at almost all sites in individuals above 40y (p<0.05). SAAID decreased with age, and more rapidly in women. Cheeks have lower SAAID scores than other body sites. MPM and RCM provide noninvasive methods for imaging skin and each method has its own advantages. Epidermal thickness and SAAID correlated with age, gender, and different body sites. MPM could also assess the degree of skin aging, which could guide the clinical treatment of patients with diffferent ages and genders in the above body sites.

Site-specific analysis of ribosomal 2'O-methylation by quantitative reverse transcription PCR under low deoxynucleotide triphosphate concentrations.

Ribose 2'O-methylation (Nm, ribomethylation) is the most abundant RNA modification present in rRNA. It has been shown that alterations in ribosomal 2'O-methylation at individual Nm sites likely reflect regulated cellular processes. Although several analytical approaches for Nm detection and profiling have been developed, a simple and affordable method for the screening and measurement of individual Nm sites in large numbers of tissue samples is required to examine their potential for clinical translation. Here, we describe a new quantitative reverse transcription PCR-based method that can sensitively assess ribomethylation levels at specific rRNA sites at single-nucleotide resolution in low input amounts of total RNA.