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Iron Dextran is a widely used iron oxide compound to treat iron‐deficiency anemia patients in the clinic. Similar to other iron oxide compounds such as Ferumoxytol, it can also be used off‐label as an intravascular magnetic resonance imaging (MRI) contrast agent due to its strong iron‐induced T2 and T2* shortening effects. In this study, we seek to evaluate the feasibility of using Iron Dextran enhanced multi‐echo susceptibility weighted imaging (SWI) MRI at 7T to image arterial and venous blood vessels in the human brain. Phantom experiments were performed to measure the r2* relaxivity for Iron Dextran in blood, based on which the SWI sequence was optimized. Pre‐ and post‐infusion MR images were acquired in human subjects from which maps of arteries and veins were extracted. The post‐contrast SWI images showed enhanced susceptibility difference between blood and the surrounding tissue in both arteries and veins. Our results showed that the proposed Iron Dextran enhanced multi‐echo SWI approach allowed the visualization of blood vessels with diameters down to ~100 μm, including small blood vessels supplying and draining small brain structures such as the hippocampus. We conclude that Iron Dextran can be an alternative iron‐based MRI contrast agent for blood vessel imaging in the human brain. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Nursing home (NH) residents with Alzheimer's disease or related dementias (ADRD) are at high risk for hospital transfer. We aimed to (1) describe characteristics and predictors of avoidable transfer of residents with ADRD and (2) explore how "what matters" influences the decision to transfer. METHODS: We applied an exploratory, mixed methods design using data collected as part of a Centers for Medicare and Medicaid Services demonstration project. Advanced practice registered nurses documented retrospective details about nursing home (NH)‐to‐hospital transfers (n = 3687) from 16 NHs. RESULTS: NH residents with ADRD had 1.22 times higher odds of having an avoidable NH‐to‐hospital transfer (odds ratio = 1.22; 95% confidence interval = 1.03, 1.45). Factors contributing to avoidable transfers were age, stage of ADRD, what matters to the resident and their family, changes in condition, and resources available in the NH. DISCUSSION: These findings highlight the need for enhanced specificity in the discussion and documentation of resident and family preferences and continued investments in the NH workforce. Highlights: This article reports on factors contributing to avoidable nursing home (NH)‐to‐hospital transfer of residents with Alzheimer's disease and related dementias (ADRD). The mixed methods design used in this study offers insight beyond what is possible using a single‐method design.Using data collected from a Centers for Medicare and Medicaid Services demonstration project, advanced practice registered nurses documented retrospective details about NH‐to‐hospital transfers (n = 3687) of residents.NH residents with ADRD were more likely to have an avoidable NH‐to‐hospital transfer. Factors contributing to avoidable transfers were age, stage of ADRD, what matters to the resident and their family, changes in condition, and resources available in the NH.These findings highlight the need for enhanced specificity in discussion and documentation of resident and family preferences and continued investments in the NH workforce. [ABSTRACT FROM AUTHOR]

Population demographic changes, alongside landscape, geographic and climate heterogeneity, can influence the timing, stability and extent of introgression where species hybridise. Thus, quantifying interactions across diverged lineages, and the relative contributions of interspecific genetic exchange and selection to divergence at the genome‐wide level is needed to better understand the drivers of hybrid zone formation and maintenance. We used seven latitudinally arrayed transects to quantify the contributions of climate, geography and landscape features to broad patterns of genetic structure across the hybrid zone of Populus trichocarpa and P. balsamifera and evaluated the demographic context of hybridisation over time. We found genetic structure differed among the seven transects. While ancestry was structured by climate, landscape features influenced gene flow dynamics. Demographic models indicated a secondary contact event may have influenced contemporary hybrid zone formation with the origin of a putative hybrid lineage that inhabits regions with higher aridity than either of the ancestral groups. Phylogenetic relationships based on chloroplast genomes support the origin of this hybrid lineage inferred from demographic models based on the nuclear data. Our results point towards the importance of climate and landscape patterns in structuring the contact zones between P. trichocarpa and P. balsamifera and emphasise the value whole genome sequencing can have to advancing our understanding of how neutral processes influence divergence across space and time. [ABSTRACT FROM AUTHOR]

Auxin dictates root architecture via the Auxin Response Factor (ARF) family of transcription factors, which control lateral root (LR) formation. In Arabidopsis, ARF7 regulates the specification of prebranch sites (PBS) generating LRs through gene expression oscillations and plays a pivotal role during LR initiation. Despite the importance of ARF7 in this process, there is a surprising lack of knowledge about how ARF7 turnover is regulated and how this impacts root architecture. Here, we show that ARF7 accumulates in autophagy mutants and is degraded through NBR1-dependent selective autophagy. We demonstrate that the previously reported rhythmic changes to ARF7 abundance in roots are modulated via autophagy and might occur in other tissues. In addition, we show that the level of co-localization between ARF7 and autophagy markers oscillates and can be modulated by auxin to trigger ARF7 turnover. Furthermore, we observe that autophagy impairment prevents ARF7 oscillation and reduces both PBS establishment and LR formation. In conclusion, we report a novel role for autophagy during development, namely by enacting auxin-induced selective degradation of ARF7 to optimize periodic root branching. Synopsis: Auxin triggers NBR1-mediated selective autophagic degradation of ARF7 to modulate periodic root branching in Arabidopsis. ARF7 is selectively degraded via NBR1-mediated autophagy Auxin regulates ARF7 co-localization with autophagosomes and subsequent turnover Defective autophagy interferes with the root clock function and lateral root formation. Auxin triggers NBR1-mediated selective autophagic degradation of ARF7 to modulate periodic root branching in Arabidopsis. [ABSTRACT FROM AUTHOR]

Purpose: Since the Choice Act in 2014, many Veterans have had greater options for seeking Veteran Affairs (VA)‐purchased care in the community. We investigated factors that influence rural Veterans' decisions regarding where to seek care. Methods: We utilized semi‐structured telephone interviews to query Veterans living in rural or highly rural areas of Midwestern states about their health care options, preferences, and experiences. Interviews were recorded and transcribed, thematically coded, and deductively analyzed using a socioecological approach. Findings: Forty rural Veterans (20 men/20 women) ages 28–76 years completed interviews in 2019. We found that rural Veterans often spoke about their relationships and interactions with providers as an important factor in deciding where to seek care. They expressed three socioecological qualities of patient–provider relationships that affected their decisions: (1) personal level—rural Veterans traveled longer distances for more compatible patient–provider relationships; (2) interpersonal level—they sought stable patient–provider relationships that encouraged familiarity, trust, and communication; and (3) organizational level—they emphasized shared identities and expertise that fostered a sense of belonging with their provider. Participants also described how impersonal interactions, status differences, and staff turnover impacted their choice of provider and were disruptive to patient–provider relationships. Conclusions: Rural Veterans' interview responses suggest exploring innovative ways to measure socioecological dimensions (i.e., personal, interpersonal, and organizational) of access‐related decisions and patient–provider relationships to better understand health care barriers and needs. Such measures align with the VA's Whole Health approach that emphasizes person‐centered care and the value of social relationships to Veterans' health. [ABSTRACT FROM AUTHOR]

Objective: Little evidence exists for the most effective conservative treatment approach for adults with myogenic temporomandibular disorders (MTMD). We aim to assess the effectiveness of cervical rehabilitation interventions on pain intensity and sensitivity in adults with MTMD compared to comparison intervention such as placebo, sham treatment, education or no intervention. Methods: For this systematic review and meta‐analysis, we searched PubMed, EMBASE, Medline, PEDro databases, forward and backward citations and grey literature studies through PROSPERO, clinical trials and data registries without language or date restrictions between inception and 1 December 2021. We selected randomised controlled trials (RCTs) based on adult populations with MTMD who had a cervical rehabilitation intervention which was defined as any conservative intervention targeting the anatomical structures of the cervical spine. The primary outcome measures for pain were self‐reported pain intensity and pain sensitivity through the pressure pain threshold (PPT) of the masseter and temporalis muscles. Secondary outcome measures of maximal mouth opening (on MMO) were included. Included studies were assessed for bias with the Cochrane risk of bias tool for randomised trials. Evidence from RCTs was synthesised to determine treatment effect size as differences between standardised mean difference (SMD) for changes in pain intensity, PPT and MMO comparing adults with MTMD who were treated with cervical rehabilitation interventions compared to a control group. This study is registered on Prospero, number CRD 42021289299. Results: Our general search yielded 2647 studies where seven RCTs met eligibility criteria with low to some concerns in their risk of bias. Pain intensity (five studies, n = 223, SMD −0.98, 95% CI −1.67 to −0.28, I2 = 79%), PPT of the masseter muscle (six studies, n = 395, SMD 0.64, 95% CI 0.43 to 0.86, I2 = 90%) and the temporalis muscles (five studies, n = 295, SMD 0.76, 95% CI 0.07 to 1.45, I2 = 84%) showed large treatment effect estimates favouring cervical rehabilitation interventions compared to no treatment, sham cervical treatment, patient education or non‐cervical neuromuscular techniques. Compared to control interventions, one type of cervical rehabilitation intervention, cervical manual therapy alone or in combination with a neck exercise program was associated with statistically significant, large treatment effect estimates on pain intensity (four studies, n = 203, SMD −1.52, 95% CI −2.50 to −0.55). Conclusions: This review found that in the short‐term, cervical rehabilitation interventions especially upper cervical MT alone or in combination with a neck exercise program are effective in improving multiple pain outcomes in adults with MTMD. However, further research is needed to measure the long‐term effects of this type of intervention. [ABSTRACT FROM AUTHOR]

Purpose: The inflow‐based vascular‐space‐occupancy (iVASO) MRI was originally developed in a single‐slice mode to measure arterial cerebral blood volume (CBVa). When vascular crushers are applied in iVASO, the signals can be sensitized predominantly to small pial arteries and arterioles. The purpose of this study is to perform a systematic optimization and evaluation of a 3D iVASO sequence on both 3 T and 7 T for the quantification of CBVa values in the human brain. Methods: Three sets of experiments were performed in three separate cohorts. (1) 3D iVASO MRI protocols were compared to single‐slice iVASO, and the reproducibility of whole‐brain 3D iVASO MRI was evaluated. (2) The effects from different vascular crushers in iVASO were assessed. (3) 3D iVASO MRI results were evaluated in arterial and venous blood vessels identified using ultrasmall‐superparamagnetic‐iron‐oxides–enhanced MRI to validate its arterial origin. Results: 3D iVASO scans showed signal‐to‐noise ratio (SNR) and CBVa measures consistent with single‐slice iVASO with reasonable intrasubject reproducibility. Among the iVASO scans performed with different vascular crushers, the whole‐brain 3D iVASO scan with a motion‐sensitized‐driven‐equilibrium preparation with two binomial refocusing pulses and an effective TE of 50 ms showed the best suppression of macrovascular signals, with a relatively low specific absorption rate. When no vascular crusher was applied, the CBVa maps from 3D iVASO scans showed large CBVa values in arterial vessels but well‐suppressed signals in venous vessels. Conclusion: A whole‐brain 3D iVASO MRI scan was optimized for CBVa measurement in the human brain. When only microvascular signals are desired, a motion‐sensitized‐driven‐equilibrium–based vascular crusher with binomial refocusing pulses can be applied in 3D iVASO. [ABSTRACT FROM AUTHOR]

Aims: We propose using glomerular filtration rate (GFR) as the physiological basis for distinguishing components of renal clearance. Methods: Gentamicin, amikacin and vancomycin are thought to be predominantly excreted by the kidneys. A mixed‐effects joint model of the pharmacokinetics of these drugs was developed, with a wide dispersion of weight, age and serum creatinine. A dataset created from 18 sources resulted in 27,338 drug concentrations from 9,901 patients. Body size and composition, maturation and renal function were used to describe differences in drug clearance and volume of distribution. Results: This study demonstrates that GFR is a predictor of two distinct components of renal elimination clearance: (1) GFR clearance associated with normal GFR and (2) non‐GFR clearance not associated with normal GFR. All three drugs had GFR clearance estimated as a drug‐specific percentage of normal GFR (gentamicin 39%, amikacin 90% and vancomycin 57%). The total clearance (sum of GFR and non‐GFR clearance), standardized to 70 kg total body mass, 176 cm, male, renal function 1, was 5.58 L/h (95% confidence interval [CI] 5.50‐5.69) (gentamicin), 7.77 L/h (95% CI 7.26‐8.19) (amikacin) and 4.70 L/h (95% CI 4.61‐4.80) (vancomycin). Conclusions: GFR provides a physiological basis for renal drug elimination. It has been used to distinguish two elimination components. This physiological approach has been applied to describe clearance and volume of distribution from premature neonates to elderly adults with a wide dispersion of size, body composition and renal function. Dose individualization has been implemented using target concentration intervention. [ABSTRACT FROM AUTHOR]

Due to a change in capital funding formula, many school boards across the Province of Ontario engaged in Accommodation Reviews to rationalize the supply of school capacity. This process led to numerous school closures and raised important policy questions regarding the economic value of a school in terms of its capitalization into property values and, by extension, how the closure of a school might affect local neighborhoods. To explore these questions, this research uses spatial hedonic methods to estimate the implicit value of accessibility to schools in the City of Hamilton, Ontario. Spatial Durbin model results provide evidence of a significant negative correlation between distance to schools and housing prices in the Canadian context. This suggests that accessibility to schools is capitalized into property values and that the closure of a neighborhood school may result in potentially significant losses of economic value in communities. [ABSTRACT FROM AUTHOR]

Psoriatic arthritis mutilans (PAM) is the rarest and most severe form of psoriatic arthritis, characterized by erosions of the small joints and osteolysis leading to joint disruption. Despite its severity, the underlying mechanisms are unknown, and no susceptibility genes have hitherto been identified. We aimed to investigate the genetic basis of PAM by performing massive parallel sequencing in sixty-one patients from the PAM Nordic cohort. We found rare variants in the NADPH oxidase 4 (NOX4) in four patients. In silico predictions show that the identified variants are potentially damaging. NOXs are the only enzymes producing reactive oxygen species (ROS). NOX4 is specifically involved in the differentiation of osteoclasts, the cells implicated in bone resorption. Functional follow-up studies using cell culture, zebrafish models, and measurement of ROS in patients uncovered that these NOX4 variants increase ROS levels both in vitro and in vivo. We propose NOX4 as the first candidate susceptibility gene for PAM. Our study links high levels of ROS caused by NOX4 variants to the development of PAM, offering a potential therapeutic target. Synopsis: Genomic analysis of Psoriatic Arthritis Mutilans (PAM) patients from the Nordic PAM cohort uncovered potentially damaging rare variants in the NOX4 gene. NOX4 belongs to a family of enzymes generating reactive oxygen species (ROS); NOX4 generates mainly hydrogen peroxide (H2O2). Three NOX4 rare variants (p.V369F, p.Y512IfsX20, and p.Y512C) affecting NOX4 functional domains were identified in four PAM patients. Enhanced differentiation and higher generation of ROS activity are observed in patient-derived osteoclasts, the cells responsible for bone resorption. NOX4 rare variants show increased generation of ROS in both zebrafish model and HEK293 cells. Increased levels of ROS, particularly H2O2, present promising therapeutic opportunities for addressing PAM. Genomic analysis of Psoriatic Arthritis Mutilans (PAM) patients from the Nordic PAM cohort uncovered potentially damaging rare variants in the NOX4 gene. NOX4 belongs to a family of enzymes generating reactive oxygen species (ROS); NOX4 generates mainly hydrogen peroxide (H2O2). [ABSTRACT FROM AUTHOR]

The viscosity and crowding of biological environment are considered vital for the correct cellular function, and alterations in these parameters are known to underly a number of pathologies including diabetes, malaria, cancer and neurodegenerative diseases, to name a few. Over the last decades, fluorescent molecular probes termed molecular rotors proved extremely useful for exploring viscosity, crowding, and underlying molecular interactions in biologically relevant settings. In this review, we will discuss the basic principles underpinning the functionality of these probes and will review advances in their use as sensors for lipid order, protein crowding and conformation, temperature and non‐canonical nucleic acid structures in live cells and other relevant biological settings. [ABSTRACT FROM AUTHOR]

Changes in telomere length are increasingly used to indicate species' response to environmental stress across diverse taxa. Despite this broad use, few studies have explored telomere length in plants. Thus, evaluation of new approaches for measuring telomeres in plants is needed. Rapid advances in sequencing approaches and bioinformatic tools now allow estimation of telomere content from whole‐genome sequencing (WGS) data, a proxy for telomere length. While telomere content has been quantified extensively using quantitative polymerase chain reaction (qPCR) and WGS in humans, no study to date has compared the effectiveness of WGS in estimating telomere length in plants relative to qPCR approaches. In this study, we use 100 Populus clones re‐sequenced using short‐read Illumina sequencing to quantify telomere length comparing three different bioinformatic approaches (Computel, K‐seek and TRIP) in addition to qPCR. Overall, telomere length estimates varied across different bioinformatic approaches, but were highly correlated across methods for individual genotypes. A positive correlation was observed between WGS estimates and qPCR, however, Computel estimates exhibited the greatest correlation. Computel incorporates genome coverage into telomere length calculations, suggesting that genome coverage is likely important to telomere length quantification when using WGS data. Overall, telomere estimates from WGS provided greater precision and accuracy of telomere length estimates relative to qPCR. The findings suggest WGS is a promising approach for assessing telomere length and, as the field of telomere ecology evolves, may provide added value to assaying response to biotic and abiotic environments for plants needed to accelerate plant breeding and conservation management. [ABSTRACT FROM AUTHOR]

Recent studies have indicated a role for circulating extracellular vesicles (EVs) in the pathogenesis of multiple diseases. However, most in vitro studies have used variable and arbitrary doses of EVs rather than interpreting EVs as an existing component of standard skeletal muscle cell culture media. The current study provides an initial investigation into the effects of circulating EVs on the metabolic phenotype of C2C12 myotubes by replacing EVs from fetal bovine serum with circulating EVs from control mice or mice with obesity and type 2 diabetes (OT2D). We report that EVs associated with OT2D decrease 2‐NBDG uptake (a proxy measure of glucose uptake) in the insulin‐stimulated state compared to controls. OT2D associated EV treatment also significantly decreased myosin heavy chain type 1 (MHCI) mRNA abundance in myotubes but had no effect on mRNA expression of any other myosin heavy chain isoforms. OT2D‐associated circulating EVs also significantly increased lipid accumulation within myotubes without altering the expression of a selection of genes important for lipid entry, synthesis, or catabolism. The data indicate that, in a severely diabetic state, circulating EVs may contribute to insulin resistance and alter gene expression in myotubes in a manner consistent with the skeletal muscle phenotype observed in OT2D. [ABSTRACT FROM AUTHOR]

Due to the overall declining costs of photovoltaic systems, market players in the operation and maintenance sector are under increasing price pressure when offering their services. The automation and standardization of maintenance and failure tickets as well as their statistical and economical evaluation are key to ensure optimal yield and long lifetime. A thorough understanding of typical faults, classified through a standardized taxonomy, can be a pathway of developing location and technology specific decision support, offering cost‐time efficient solutions to reduce component downtime and costs in case of failure appearance. A useful method for this approach is the Cost Priority Number, a methodology to assess technical failures and their economic impact in energy systems. In this work, this method is further improved to be applied to individual use cases to make it useful in the actual operation of PV plants. A standardized ticket taxonomy for the operational phase of PV systems has been developed where more than 35,000 PV systems' tickets have been statistically evaluated, and a fully automated methodology to calculate the cost of individual maintenance tickets has been developed. [ABSTRACT FROM AUTHOR]

The viscosity and crowding of biological environment are considered vital for the correct cellular function, and alterations in these parameters are known to underly a number of pathologies including diabetes, malaria, cancer and neurodegenerative diseases, to name a few. Over the last decades, fluorescent molecular probes termed molecular rotors proved extremely useful for exploring viscosity, crowding, and underlying molecular interactions in biologically relevant settings. In this review, we will discuss the basic principles underpinning the functionality of these probes and will review advances in their use as sensors for lipid order, protein crowding and conformation, temperature and non‐canonical nucleic acid structures in live cells and other relevant biological settings. [ABSTRACT FROM AUTHOR]

The plastic ability for a range of phenotypes to be exhibited by the same genotype allows organisms to respond to environmental variation and may modulate fitness in novel environments. Differing capacities for phenotypic plasticity within a population, apparent as genotype by environment interactions (GxE), can therefore have both ecological and evolutionary implications. Epigenetic gene regulation alters gene function in response to environmental cues without changes to the underlying genetic sequence and likely mediates phenotypic variation. DNA methylation is currently the most well described epigenetic mechanism and is related to transcriptional homeostasis in invertebrates. However, evidence quantitatively linking variation in DNA methylation with that of phenotype is lacking in some taxa, including reef‐building corals. In this study, spatial and seasonal environmental variation in Bonaire, Caribbean Netherlands was utilized to assess relationships between physiology and DNA methylation profiles within genetic clones across different genotypes of Acropora cervicornis and A. palmata corals. The physiology of both species was highly influenced by environmental variation compared to the effect of genotype. GxE effects on phenotype were only apparent in A. cervicornis. DNA methylation in both species differed between genotypes and seasons and epigenetic variation was significantly related to coral physiological metrics. Furthermore, plastic shifts in physiology across seasons were significantly positively correlated with shifts in DNA methylation profiles in both species. These results highlight the dynamic influence of environmental conditions and genetic constraints on the physiology of two important Caribbean coral species. Additionally, this study provides quantitative support for the role of epigenetic DNA methylation in mediating phenotypic plasticity in invertebrates. [ABSTRACT FROM AUTHOR]

Atlantic tarpon Megalops atlanticus are highly migratory sportfish that support recreational fisheries throughout their range. In US waters, juveniles can be found in coastal and estuarine habitats along the Gulf of Mexico and Atlantic seaboard, with temperature limiting their northern latitudinal distribution. Juveniles may overwinter in these areas during the first several years of life. Low temperatures are known to cause mortality in adults, but the challenges of temperature are less understood for juveniles. Furthermore, salinity, which can change dramatically in these habitats, may have a synergistic effect with temperature. To examine the physiological effects of temperature and salinity on juvenile tarpon, wild fish were acclimated to a range of conditions that potentially occur in the northern range of their estuarine habitats. The haematology of juvenile tarpon was examined in two salinity (≤2 and ≥30 ppt) and temperature (15 and 25°C) treatments, followed by a low‐temperature tolerance test. After 2 weeks in treatment conditions, blood samples were analysed for haematocrit, pH, red blood cell concentration, haemoglobin content and plasma osmolality. Increased plasma osmolality was observed in fish at low temperature (15°C compared to 25°C) and at high salinity (≥30 ppt compared to ≤2 ppt). Blood pH was increased at 15°C compared to 25°C, with the highest pH at 15°C and low salinity. Haemoglobin, haematocrit and red blood cell concentration were higher at 25°C than 15°C, with haemoglobin lowest at 15°C and low salinity. For the low‐temperature tolerance test, all fish were acclimated to 15°C for 2 weeks, then transferred to separate tanks where temperature was gradually decreased at 0.9 ± 0.1°C/h until fish lost equilibrium. Fish at low salinity lost equilibrium more rapidly (1 ppt, 12.65 ± 0.46°C) than fish at high salinity (30 ppt, 11.26 ± 0.14°C). The results indicate juvenile tarpon are susceptible to low temperature, which is exacerbated by low salinity, findings useful in the assessment of juvenile tarpon overwintering habitat. [ABSTRACT FROM AUTHOR]

The number of 2D systems based on Mn and C atoms has been growing significantly due to the magnetic and electronic properties that these monolayers present. In this work, a new Mn‐C monolayer by density functional theory is proposed. The MnC4 stability is studied by the formation energy formalism to compare with other reported Mn‐C monolayers. Our analysis points that the MnC4 monolayer stabilizes at extremely rich C conditions. Also, the MnC4 monolayer possess positive phonon branches, evidencing its dynamic stability. Further, it confirms that this monolayer is also stable up to 300 K. This new monolayer has an antiferromagnetic alignment with spin‐channels along the [‐110] direction and metallic behavior, being a strong candidate in the formation of exchange‐biased systems when forming a van der Waals heterojunction with other Ferromagnetic materials. [ABSTRACT FROM AUTHOR]

Objective: Immunocompromised patients with chronic inflammatory disease (CID) may have experienced additional psychosocial burden during the COVID‐19 pandemic due to their immunocompromised status. This study was undertaken to determine if vaccination would result in improved patient‐reported outcomes longitudinally among individuals with CID undergoing SARS–CoV‐2 vaccination regardless of baseline anxiety. Methods: Data are from a cohort of individuals with CID from 2 sites who underwent SARS–CoV‐2 vaccination. Participants completed 3 study visits before and after 2 messenger RNA vaccine doses in the initial vaccination series when clinical data were collected. Patient‐reported outcomes were measured using the Patient‐Reported Outcomes Measurement Information System 29‐item Health Profile and expressed as T scores, with 2 groups stratified by high and low baseline anxiety. Mixed‐effects models were used to examine longitudinal changes, adjusting for age, sex, and study site. Results: A total of 72% of the cohort was female with a mean ± SD age of 48.1 ± 15.5 years. Overall, sleep disturbance improved following both doses of SARS–CoV‐2 vaccinations, and anxiety decreased after the second dose. Physical function scores worsened but did not meet the minimally important difference threshold. When stratifying by baseline anxiety, improvement in anxiety, fatigue, and social participation were greater in the high anxiety group. Physical function worsened slightly in both groups, and sleep disturbance improved significantly in the high anxiety group. Conclusion: Sleep disturbance decreased in a significant and meaningful way in patients with CID upon vaccination. In patients with higher baseline anxiety, social participation increased, and anxiety, fatigue, and sleep disturbance decreased. Overall, results suggest that SARS–CoV‐2 vaccination may improve mental health and well‐being, particularly among those with greater anxiety. [ABSTRACT FROM AUTHOR]

Hemicelluloses are a major component of lignocellulosic biomass. Different sugars can be obtained from hemicelluloses: xylose, arabinose, galactose, mannose, glucose. Their catalytic hydrogenation produces polyols: xylitol, arabinitol, dulcitol, mannitol, sorbitol, which are valuable chemicals and platform molecules. In this paper, the hydrogenation of sugars was investigated with a Ru/TiO2 catalyst. The influence of temperature, pressure, xylose concentration and catalyst amount was studied for xylose hydrogenation and a Langmuir‐Hinshelwood kinetic model was designed. The comparative study of five hemicellulose sugars showed a strong impact of sugar structure on hydrogenation rate: hexoses (glucose, mannose, galactose) react slower than pentoses (xylose, arabinose). [ABSTRACT FROM AUTHOR]

Introduction: The Agency for Healthcare Research and Quality (AHRQ) Evidence‐based Practice Center (EPC) Program produces evidence reports to assist health systems in improving patient care. To make EPC evidence reports more accessible and usable, AHRQ convened a panel of learning health system (LHS) senior leaders to develop two web‐based tools—a table‐based tool presenting high‐level results, and a graphical display that presented detailed data—to disseminate the reports and test the tools. Researchers examined (1) the context under which interview participants reviewed and used the evidence reported by the tools, (2) their experiences using the tools, (3) the tools' influence on clinical practice, and (4) how the tools could be improved. Methods: Researchers collected and inductively analyzed qualitative data from tool implementation meetings with six LHSs and interviews with 27 LHS leaders and clinical staff who used the tools. Researchers used website utilization metrics to augment qualitative results. Results: The tools were efficient, complementary, and useful sources of summarized evidence to promote system change, educate trainees and clinicians, inform research, and support shared decision making with patients and families. Clinical leaders appreciated the evidence review thoroughness and quality and viewed AHRQ as a trusted source of information. However, many felt the tools were not practical for bedside use because of their complex content. Participants also noted the reports had limited evidence strength and robustness. They suggested optimizing the tools for mobile device use to facilitate tool uptake and developing training resources about tool navigation and statistical content interpretation. Conclusions: LHSs found the tools to be useful resources for making the EPC Program reports more accessible to and usable for health system leaders. The tools have the potential to meet some, but not all, LHS evidence needs. Their value depends on reports' usefulness, which ultimately depends on the evidence quality. [ABSTRACT FROM AUTHOR]

Atrazine (2‐chloro‐4‐ethylamino‐6‐isopropylamino‐s‐triazine) has been described as a potential toxic for dopaminergic metabolism both in vivo and in vitro. Its main metabolite diamino‐chloro triazine (DACT) has been shown to achieve higher levels in brain tissue than atrazine. The aim of this study was to evaluate the in vitro effects of atrazine and DACT on striatal mitochondrial function, active oxygen species generation, and nitric oxide (NO) content. Incubation of mitochondria with atrazine (10 µM) was not able to modify oxygen consumption. However, a 50% increase in malate‐glutamate state 4 respiratory rates was observed after DACT treatment (100 µM) without changes in respiratory state 3. Atrazine was able to inhibit complex I–III activity by 30% and DACT induced a tendency to decrease by 17% in the striatum. Regarding reactive oxygen species (ROS), DACT increased H2O2 production by 43%. Also, superoxide anion levels were higher (14%) after atrazine exposure than in control mitochondria. Incubation of striatal mitochondria with atrazine and DACT induced membrane depolarization by 15% and 19%, respectively. Also, atrazine increased NO content by 10% but no significant changes were observed after exposure of mitochondria to DACT. Glutathione peroxidase activity was inhibited (56%) by DACT and atrazine inhibited superoxide dismutase activity by 60%. Also, cardiolipin oxidation (15%) was observed after atrazine treatment. Summing up, the obtained results suggest that in vitro atrazine and DACT induce ROS production affecting striatal mitochondrial function. The atrazine effects would be attributed to a direct effect on the mitochondrial respiratory chain and superoxide dismutase activity while DACT appears to disturb glutathione‐related enzyme system. [ABSTRACT FROM AUTHOR]

Objective: Little is known regarding the reactogenicity and related SARS–CoV‐2 vaccine response in patients with chronic inflammatory disease (CID). Our objective was to characterize the adverse event profile of CID patients following SARS–CoV‐2 vaccination and understand the relationship between reactogenicity and immunogenicity of SARS–CoV‐2 vaccines. Methods: CID patients and healthy controls eligible to receive messenger RNA (mRNA) SARS–CoV‐2 vaccines participated in 3 study visits (pre‐vaccine, after dose 1, and after dose 2) in which blood and clinical data were collected. Assessment of adverse events were solicited within 7 days of receiving each dose. Serum anti–SARS–CoV‐2 spike IgG ± antibody titers were quantified following vaccination. Statistical analysis was performed utilizing mixed models and tobit regressions, with adjustment for covariates. Results: The present study included 441 participants (322 CID patients and 119 control subjects). Compared to controls, CID patients reported greater symptom severity after dose 1 (P = 0.0001), including more myalgia and fatigue (P < 0.05). For immunogenicity, a higher symptom severity after dose 1 and a higher number of symptoms after dose 2 was associated with higher antibody titers (P ≤ 0.05). Each increase of 1 symptom was associated with a 15.1% increase in antibody titer. Symptom association was strongest with site pain after dose 1 (105%; P = 0.03) and fatigue after dose 2 (113%; P = 0.004). Conclusion: Patients with CID have a distinct reactogenicity profile following SARS–CoV‐2 vaccination compared to controls. Furthermore, there is an association between increased reactogenicity and increased vaccine response. This finding may speak to the more variable immunogenicity in CID patients and may be an important indicator of vaccine response to the novel SARS–CoV‐2 vaccines. [ABSTRACT FROM AUTHOR]

Surface passivating thin films are crucial for limiting the electrical losses during charge carrier collection in silicon photovoltaic devices. Certain dielectric coatings of more than 10 nm provide excellent surface passivation, and ultra‐thin (<2 nm) dielectric layers can serve as interlayers in passivating contacts. Here, ultra‐thin passivating films of SiO2, Al2O3, and HfO2 are created via plasma‐enhanced atomic layer deposition and annealing. It is found that thin negatively charged HfO2 layers exhibit excellent passivation properties—exceeding those of SiO2 and Al2O3—with 0.9 nm HfO2 annealed at 450 °C providing a surface recombination velocity of 18.6 cm s−1. The passivation quality is dependent on annealing temperature and layer thickness, and optimum passivation is achieved with HfO2 layers annealed at 450 °C measured to be 2.2–3.3 nm thick which give surface recombination velocities ≤2.5 cm s−1 and J0 values of ≈14 fA cm−2. The superior passivation quality of HfO2 nanolayers makes them a promising candidate for future passivating contacts in high‐efficiency silicon solar cells. [ABSTRACT FROM AUTHOR]

Objective: To assess whether patients with autoimmune disease would accept advanced practice providers (APPs) as an option to fill the growing shortage of rheumatologists.Methods: We administered a cross-sectional survey to 500 patients or parents of children who reported having been diagnosed with qualifying autoimmune conditions and who had seen their primary rheumatology providers in the past 6 months. Respondents self-reported whether their primary providers were rheumatologists or APPs. Our analysis compared the attitude and experience of the patients whose primary rheumatology providers were APPs with those of patients whose primary providers were rheumatologists.Results: Of respondents, 36.8% reported having APPs as primary rheumatology providers. Patients of APPs were significantly more likely to arrive at their provider's office in 15 minutes or less (P < 0.01) and to be able to schedule routine and urgent appointments sooner (P = 0.02 and 0.05, respectively). There were no significant differences in overall patient experience of care between provider types. Most patients rated their providers highly, but those who saw rheumatologists rated their providers significantly higher (P < 0.01). Patients of APPs were significantly more likely than patients of rheumatologists to prefer to see APPs over rheumatologists (P < 0.01) and to recommend APPs (P < 0.01).Conclusion: APPs may improve access to care and, regardless of provider type, patients rated their overall experience of care similarly. Overall, patient attitudes toward APPs were positive regardless of provider type, although APP patients held more positive overall attitudes toward APPs than did rheumatologist patients. [ABSTRACT FROM AUTHOR]

Background: Hartmann's procedure (HP) is used in surgical emergencies such as colonic perforation and colonic obstruction. "Temporary" colostomy performed during HP is not always reversed in part due to potential morbidity and mortality associated with reversal. There are several contributing factors for patients requiring a permanent colostomy following HP. Therefore, there is still some discussion about which technique to use. The aim of this study was to evaluate perioperative variables of patients undergoing Hartmann's reversal using a laparoscopic and open approach. Methods: The multicenter retrospective cohort study was done between January 2009 and December 2019 at 14 institutions globally. Patients who underwent Hartmann's reversal laparoscopic (LS) and open (OS) approaches were evaluated and compared. Sociodemographic, preoperative, intraoperative variables, and surgical outcomes were analyzed. The main outcomes evaluated were 30‐day mortality, length of stay, complications, and postoperative outcomes. Results: Five hundred and two patients (264 in the LS and 238 in the OS group) were included. The most prevalent sex was male in 53.7%, the most common indication was complicated diverticular disease in 69.9%, and 85% were American Society of Anesthesiologist (ASA) II‐III. Intraoperative complications were noted in 5.3% and 3.4% in the LS and OS groups, respectively. Small bowel injuries were the most common intraoperative injury in 8.3%, with a higher incidence in the OS group compared with the LS group (12.2% vs. 4.9%, p < 0.5). Inadvertent injuries were more common in the small bowel (3%) in the LS group. A total of 17.2% in the OS versus 13.3% in the LS group required intensive care unit (ICU) admission (p = 0.2). The most frequent postoperative complication was ileus (12.6% in OS vs. 9.8% in LS group, p = 0.4)). Reintervention was required mainly in the OS group (15.5% vs. 5.3% in LS group, p < 0.5); mortality rate was 1%. Conclusions: Laparoscopic Hartmann's reversal is safe and feasible, associated with superior clinical outcomes compared with open surgery. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the long‐term oncological outcomes of patients with upper tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU) and the impact of diagnostic ureteroscopy (URS) on survival outcomes. Materials and Methods: A retrospective analysis of all consecutive patients undergoing RNU for suspected UTUC at a UK tertiary referral centre from a prospectively maintained database was conducted. The primary outcome measures were 5‐ and 10‐year cancer‐specific survival (CSS). The secondary outcomes were: overall survival (OS), recurrence‐free survival (RFS), impact of prior diagnostic URS on OS, CSS and intravesical RFS (intravesical‐RFS), and predictors of intravesical recurrence. Statistical analysis was performed in R using the 'survminer' and 'survival' packages. The Kaplan–Meier method was used to calculate survival functions and these were expressed in graphical form. Uni‐/multivariate survival analyses were performed using the Cox proportional hazard regression model. Statistical significance in this study was set at P < 0.05. Results: A total of 422 patients underwent RNU with confirmed UTUC. The median (interquartile range) follow‐up of patients with confirmed UTUC was 9.2 (5.6–12.7) years. The 5‐ and 10‐year CSS rates were 70.5% (95% confidence interval [CI] 65.9–74.9) and 67.1% (95% CI 62.4–71.6), respectively. OS (HR 1.04 [95% CI 0.78–1.38]; P = 0.46) and CSS (HR 0.96 [95% CI 0.68–1.34]; P = 0.81) were similar in the diagnostic URS and the direct RNU cohorts. intravesical RFS was superior for the direct RNU cohort (HR 1.94 [95% CI 1.19–3.17]; P = 0.008). In multivariate analysis, prior URS, T2 stage, proximal ureter tumour and bladder cancer history were predictors of metachronous bladder recurrence. Conclusion: This single‐centre retrospective cohort study reports the long‐term oncological outcomes of RNU with a median follow‐up of 9.2 years, serving as a reference standard in counselling patients undergoing RNU. Stage and grade of the RNU specimen were the only two studied factors that appeared to adversely impact long‐term CSS and OS. Our results suggest that the risk of intravesical recurrence is increased nearly twofold in patients who have undergone diagnostic URS prior to RNU. Prior URS, however, does not appear to adversely impact long‐term CSS and OS. The authors suggest that a risk‐stratified approach be adopted, wherein diagnostic URS is offered only in equivocal cases. [ABSTRACT FROM AUTHOR]

Keywords: Presenilin-1; Alzheimer's disease; parkinsonism; motor fluctuations; levodopa-induced dyskinesia EN Presenilin-1 Alzheimer's disease parkinsonism motor fluctuations levodopa-induced dyskinesia 335 337 3 02/23/23 20230201 NES 230201 Pathogenic variants in the Presenilin 1 gene ( I PSEN1 i , OMIM#607822) represent the most frequent cause of Dominant Inherited Alzheimer's disease (DIAD),[1] with more than 200 pathogenic variants reported and associated with an age at onset before 50 years, with some cases reported even before 40.[2] Movement disorders, mainly myoclonus and parkinsonism, can occur in the early course of the disease and affect up to 30% of patients.[[2]] Furthermore, some of the cases with parkinsonism have been reported to be levodopa-responsive and to develop early motor fluctuations and dyskinesias.[4] However, I PSEN1 i variants are seldom considered in the assessment of patients with early-onset parkinsonism.[5] We describe the case of a patient with a mixed clinical phenotype of early-onset dementia and parkinsonism with motor complications due to a pathogenic variant in the I PSEN1 i gene. In summary, pathogenic variants in the I PSEN1 i gene might represent an underrecognized cause of early-onset dementia with parkinsonism that can present with marked motor fluctuations and dyskinesia. Alzheimer's disease, parkinsonism, motor fluctuations, levodopa-induced dyskinesia, Presenilin-1. [Extracted from the article]

Background: Use of gabapentinoids is increasing. Following recent case reports, we investigated a putative risk of parkinsonism with pregabalin or gabapentin.Methods: A disproportionality analysis of 5,653,547 individual case safety reports in the World Health Organization individual case safety report database, VigiBase, compared all patients with parkinsonism who were receiving gabapentinoids with other patients. Results are shown as reporting odds ratios and the information component, an indicator of disproportionate Bayesian reporting. Sensitivity analyses included comparisons with drugs used for similar indications (amitriptyline, duloxetine) and exclusion of drugs that induce parkinsonism.Results: Among 5,653,547 reports, 4925 parkinsonism reports were found with pregabalin and 4881 with gabapentin. Gabapentin and pregabalin were associated with increased reporting odds ratio (2.16 [2.10-2.23], 2.43 [2.36-2.50]). Similar trends were found using information components after excluding drugs that induce parkinsonism and for pregabalin compared with amitriptyline or duloxetine.Conclusions: This study found that gabapentinoids (particularly pregabalin) can be associated with parkinsonism. © 2019 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Impaired keratinocyte functions are major factors that are responsible for delayed diabetic wound healing. In addition to its antimicrobial activity, the antimicrobial peptide derived from insulin‐like growth factor‐binding protein 5 (AMP‐IBP5) activates mast cells and promotes keratinocyte and fibroblast proliferation and migration. However, its effects on diabetic wound healing remain unclear. Human keratinocytes were cultured in normal or high glucose milieus. The production of angiogenic growth factor and cell proliferation and migration were evaluated. Wounds in normal and streptozotocin‐induced diabetic mice were monitored and histologically examined. We found that AMP‐IBP5 rescued the high glucose‐induced attenuation of proliferation and migration as well as the production of angiogenin and vascular endothelial growth factors in keratinocytes. The AMP‐IBP5‐induced activity was mediated by the epidermal growth factor receptor, signal transducer and activator of transcription 1 and 3, and mitogen‐activated protein kinase pathways, as indicated by the inhibitory effects of pathway‐specific inhibitors. In vivo, AMP‐IBP5 markedly accelerated wound healing, increased the expression of angiogenic factors and promoted vessel formation in both normal and diabetic mice. Overall, the finding that AMP‐IBP5 accelerated diabetic wound healing by protecting against glucotoxicity and promoting angiogenesis suggests that AMP‐IBP5 might be a potential therapeutic target for treating chronic diabetic wounds. [ABSTRACT FROM AUTHOR]

Background: Operative vaginal birth represents an alternative to address problems during the second stage of labor. Obstetricians have access to three different instruments: forceps, vacuum, and spatulas. Objective: To evaluate the safety and effectiveness of the use of spatulas for operative vaginal birth. Search strategy: MEDLINE/PubMed, Embase, CENTRAL, LILACS, SciELO, ClinicalTrials.gov, and OpenGrey. Selection criteria: Randomized controlled studies and non‐randomized controlled studies (NRS) were included. Data collection and analysis: Studies were independently assessed for inclusion, data extraction, and risk of bias. Main results: Nine NRS (n = 16 497 women) compared the use of spatulas versus forceps. Low‐certainty evidence suggests that spatulas were not different in terms of failed operative vaginal delivery rate (odds ratio [OR] 0.89, 95% confidence interval [CI] 0.53–1.52), but may decrease the incidence of birth canal trauma (OR 0.70, 95% CI 0.54–0.91), birth canal laceration (OR 0.50, 95% CI 0.28–0.91), and neonatal soft‐tissue injury (OR 0.19, 95% CI 0.13–0.29). Six NRS (n = 2992 women) compared the use of spatulas versus vacuum. Low‐quality evidence suggests that spatulas may decrease failed operative vaginal delivery rate (OR 0.10, 95% CI 0.04–0.26). There were no apparent differences in other maternal and neonatal outcomes. Conclusion: Low‐certainty evidence suggests that spatulas could be a safe and effective alternative for operative vaginal birth. Evidence from non‐randomized controlled studies suggests that spatulas could be a safe and effective alternative for operative vaginal birth. [ABSTRACT FROM AUTHOR]

The data from the K‐12 School Shooting Database (K‐12 SSDB) of 1,544 school shootings were used to explore patterns of mass school shootings in the United States, with particular focus on the interplay between relevant predictors of these tragic events. Through a conjunctive analysis of case configurations (CACC), results from the current study show that (1) mass school shootings are rare and cluster significantly among dominant situational profiles, defined by the unique combination of variables attributes; (2) mass school shootings are never pre‐planned and in no case involve hostages. Current findings are discussed in light of existing school shooting scholarship and recommendations for policy and future areas of research are offered. [ABSTRACT FROM AUTHOR]

More than a 60% increase in crop production is required by the 2050's to feed a growing world population. Understanding how plant functional traits and field management affect crop yields has the potential to improve agricultural productivity, minimize economic and environmental losses, and maximize food security. We explored the influence of winter wheat root characteristics and management on winter wheat growth, yield, and profit using a mechanistic and well‐tested ecosystem and crop model, ecosys. We applied and further tested ecosys at an agricultural farm growing winter wheat in Ardmore, Oklahoma, United States. The model accurately predicted observed shoot carbon (R2 = 0.95), soil moisture (R2 = 0.67), soil temperature (R2 = 0.91), and yield (percent error = 17%). Numerical optimization experiments were conducted to explore potential improvements of winter wheat yield and profit by modifying root characteristics, including root radius and root:shoot carbon transfer conductance, and fertilizer inputs. Our results show the potential for simultaneously improving winter wheat yields and profits. The optimum conditions were found to be in the range of root radius between 0.1 and 0.3 mm, carbon transfer conductance between 0.004 and 0.01 h−1, and the currently applied fertilizer rate of 112 kg ha−1. Under these conditions, improvements in yields and profits of up to approximately 25% and 110%, respectively, were modeled compared to those under baseline root traits. These improvements were achieved by impoverishing root structures, thereby increasing nutrient allocation to grains. Our results also demonstrate and motivate model structures that integrate the complex network of plant physiology, soil nutrient biogeochemistry, hydrology, and management. Plain Language Summary: To meet projected food demands for a growing world population, crop yields need to be doubled by the 2050's. Although aboveground crop traits have been widely studied to improve crop yields, the "invisible" part of the crop, root systems, is not well studied. In this study, we performed a numerical optimization of root traits (such as root radius and carbon transfer conductance between shoot and root) and fertilizer application rate using a well‐tested coupled ecohydrological and biogeochemical model. We found that engineering deeper wheat root structures could improve yields and profits by 25% and 110%, respectively, compared to the present day without additional fertilizer inputs. These improvements were accompanied by almost no change in nitrogen losses via surface N2O fluxes, indicating that the optimized root traits were an environmentally friendly option to meet future food demands. Key Points: Improved water and nitrogen use efficiencies were modeled when optimizing root radius and root:shoot carbon transfer conductanceOptimizing root traits could improve wheat yields and profits without considerable nitrogen losses via nitrate leaching and N2O emissionsThese optimized root traits imply some loss of resilience to environmental stressors, such as drought [ABSTRACT FROM AUTHOR]

Purpose: A new regularizer is proposed for the magnitude least‐squares optimization algorithm, to ensure robust parallel transmit RF shimming and small‐tip‐angle multispoke pulse designs for ultrahigh‐field MRI. Methods: A finite‐difference regularization term is activated as an additional regularizer in the iterative magnitude‐least‐squares based pulse design algorithm when an unwanted flip angle null distribution is detected. Both simulated and experimental B1+ maps from different transmit arrays and different human subjects at 7 T were used to evaluate the proposed algorithm. The algorithm was further demonstrated in experiment with dynamic multislice RF shimming for a single‐shot gradient‐echo EPI for human functional MRI at 7 T. Results: The proposed finite‐difference regularizer effectively prevented excitation null to be formed for RF shimming and small‐tip‐angle multispoke pulses, and improved the latter with a monotonic trade‐off relationship between flip angle error and RF power. The proposed algorithm was demonstrated to be effective with several head‐array geometries by simulation and with a commercial head array with 12 healthy human subjects by experiment. During a functional MRI scan at 7 T with dynamic RF shimming, the proposed algorithm ensured high image SNR throughout the human brain, compared with near‐complete local signal loss by the conventional magnitude‐least‐squares algorithm. Conclusion: Using finite‐difference regularization to avoid unwanted solutions, the robustness of RF shimming and small‐tip‐angle multispoke pulse design algorithms are improved, with better flip angle homogeneity and a monotonic trade‐off relationship between flip angle error and RF power. [ABSTRACT FROM AUTHOR]

The novel SARS‐CoV2 has disrupted health systems and the economy, and public health interventions to slow its spread have been costly. How and when to ease restrictions to movement hinges in part on whether SARS‐CoV2 will display seasonality due to variations in temperature, humidity, and hours of sunshine. Here, we address this question by means of a spatio‐temporal analysis in Spain of the incidence of COVID‐19, the disease caused by the virus. Use of spatial Seemingly Unrelated Regressions (SUR) allows us to model the incidence of reported cases of the disease per 100,000 population as an interregional contagion process, in addition to a function of temperature, humidity, and sunshine. In the analysis we also control for GDP per capita, percentage of older adults in the population, population density, and presence of mass transit systems. The results support the hypothesis that incidence of the disease is lower at higher temperatures and higher levels of humidity. Sunshine, in contrast, displays a positive association with incidence of the disease. Our control variables also yield interesting insights. Higher incidence is associated with higher GDP per capita and presence of mass transit systems in the province; in contrast, population density and percentage of older adults display negative associations with incidence of COVID‐19. [ABSTRACT FROM AUTHOR]

The vaquita is the most critically endangered marine mammal, with fewer than 19 remaining in the wild. First described in 1958, the vaquita has been in rapid decline for more than 20 years resulting from inadvertent deaths due to the increasing use of large‐mesh gillnets. To understand the evolutionary and demographic history of the vaquita, we used combined long‐read sequencing and long‐range scaffolding methods with long‐ and short‐read RNA sequencing to generate a near error‐free annotated reference genome assembly from cell lines derived from a female individual. The genome assembly consists of 99.92% of the assembled sequence contained in 21 nearly gapless chromosome‐length autosome scaffolds and the X‐chromosome scaffold, with a scaffold N50 of 115 Mb. Genome‐wide heterozygosity is the lowest (0.01%) of any mammalian species analysed to date, but heterozygosity is evenly distributed across the chromosomes, consistent with long‐term small population size at genetic equilibrium, rather than low diversity resulting from a recent population bottleneck or inbreeding. Historical demography of the vaquita indicates long‐term population stability at less than 5,000 (Ne) for over 200,000 years. Together, these analyses indicate that the vaquita genome has had ample opportunity to purge highly deleterious alleles and potentially maintain diversity necessary for population health. see also the Perspective by Annabel Whibley [ABSTRACT FROM AUTHOR]

Background. Variability in chronic kidney disease (CKD) progression is a well-known phenomenon that underlines the importance of characterizing the said outcome in specific populations. Our objectives were to evaluate changes in the estimated glomerular filtration rate (eGFR) over time and determine the frequency of dialysis admission and factors associated with this outcome, to estimate the rate of program's loss-to-follow-up and the probability of transition between CKD stages over time. Methods. The study type was an observational analytic retrospective cohort in patients treated in a CKD prevention program in Bogota, Colombia, between January 1, 2009, and December 31, 2013, with follow-up until December 31, 2018. Adult participants of 18 years of age or older with diagnosed CKD stages G3 or G4 were enrolled into a prevention program. For each patient, the rate of progression of CKD in ml/min/1.73 m2/year was estimated using the ordinary least-squares method. Dialysis initiation and program's loss-to-follow-up rates were calculated. Heat maps were used to present probabilities of transitioning between various CKD stages over time. Survival model with competing risks was used to evaluate factors associated with dialysis initiation. Results. A total of 2752 patients met inclusion criteria and contributed with 14133 patient-years of follow-up and 200 dialysis initiation events, which represents a rate of 1.4 events per 100 patient-years (95% CI 1.2 to 1.6). The median change of the eGFR for the entire cohort was −0.47 ml/min/1.73 m2 per year, and in the diabetic population, it was −1.55 ml/min/1.73 m2 per year. The program's loss-to-follow-up rate was 2.6 events per 100 patient-years (95% CI 2.3 to 2.9). Probabilities of CKD stage transitions are presented in heat maps. Female sex, older age, baseline eGFR, and serum albumin were associated with lower risk of dialysis initiation while CKD etiology diabetes, cardiovascular disease history, systolic blood pressure, blood urea nitrogen, and LDL cholesterol were associated with a higher likelihood of dialysis initiation. Conclusions. A CKD secondary prevention program's key indicator is reported here, such as dialysis initiation, progression rate, and program drop-out; CKD progression appears to be correlated with diabetic status and timing of referral into the preventive program. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic relapsing inflammatory cutaneous disease that is often associated with other atopic symptoms, such as food allergy, allergic rhinitis and asthma, leading to significant morbidity and healthcare costs. The pathogenesis of AD is complicated and multifactorial. Although the aetiology of AD remains incompletely understood, recent studies have provided further insight into AD pathophysiology, demonstrating that the interaction among genetic predisposition, immune dysfunction and environmental provocation factors contributes to its development. However, the increasing prevalence of AD suggests that environmental factors such as irritation and cutaneous infection play a crucial role in triggering and/or aggravating the disease. Of note, AD skin is susceptible to bacterial, fungal and viral infections, and microorganisms may colonize the skin and aggravate AD symptoms. Overall, understanding the mechanisms by which these risk factors affect the cutaneous immunity of patients with AD is of great importance for developing a precision medicine approach for treatment. This review summarizes recent developments in exogenous factors involved in the pathogenesis of AD, with special emphasis on irritants and microbial infections. [ABSTRACT FROM AUTHOR]

Currently, studies about the CO2 gas injection improve the production efficiency of crude oil. The surface interaction between CO2 and thin films is a large area of research in the scientific community. In this work, we are showing that The TiZrN (coating) + Si (substrate) system immersed on environments of fully CO2 can interact to below 400°C temperature, because the TiZrN (coating) + Si (substrate) system is broken to temperatures above of the 400°C. The Ti2p, Zr3d, N1s, O1s, and C1s narrow spectra are shown, which illustrate the evolution of TiZrN to TiNx, TiOx, and TiONx compounds and afterwards to TiO2 and ZrO2 phases. TiNx, TiOx, and TiONx compounds are responsible for the increase of the micro‐hardness (measured through Vickers Hardness Testing) of the system (TiZrN [coating] + Si [substrate]) due to that are found at 400°C thermal treatment. Topographical images obtained by atomic force microscopy showed an increase of the surface roughness due to the thermal treatment. Scanning electron microscopy demonstrated that sample submit to 600°C temperature suffered fracture with small indentations. [ABSTRACT FROM AUTHOR]

Purpose: The circulation of cerebrospinal fluid (CSF) is closely associated with many aspects of brain physiology. When gadolinium(Gd)‐based contrast is administered intravenously, pre‐ and post‐contrast MR signal changes can often be observed in the CSF at certain locations within the intra‐cranial space, mainly due to the lack of a blood‐brain barrier in the dural blood vessels. This study aims to develop and systemically optimize MRI sequences that can detect dynamic signal changes in the CSF after Gd administration with a sub‐millimeter spatial resolution, a temporal resolution of <10 s, and whole brain coverage. Methods: Bloch simulations were performed to determine optimal imaging parameters for maximum CSF contrast before and after Gd injection. Simulations were validated with phantom scans. An optimized turbo‐spin‐echo (TSE) sequence was performed on healthy volunteers on 3T and 7T. Results: Simulation results agreed well with phantom scans. In human scans, dynamic signal changes after Gd injection in the CSF were detected at several locations where cerebral lymphatic vessels were identified in previous studies. The concentration of Gd in CSF in these regions was estimated to be approximately 0.2 mmol/L. Conclusion: Dynamic signal changes induced by the distribution of Gd in the CSF can be detected in healthy human subjects with an optimized TSE sequence. The proposed methodology does not rely on any particular theory on CSF circulation. We expect it to be useful for studies on CSF circulation and cerebral lymphatic vessels in the brain. [ABSTRACT FROM AUTHOR]