Differential endothelial cell cycle status in postnatal retinal vessels revealed using a novel PIP-FUCCI reporter and zonation analysis.

Cell cycle regulation is critical to blood vessel formation and function, but how the endothelial cell cycle integrates with vascular regulation is not well-understood, and available dynamic cell cycle reporters do not precisely distinguish all cell cycle stage transitions in vivo. Here we characterized a recently developed improved cell cycle reporter (PIP-FUCCI) that precisely delineates S phase and the S/G2 transition. Live image analysis of primary endothelial cells revealed predicted temporal changes and well-defined stage transitions. A new inducible mouse cell cycle reporter allele was selectively expressed in postnatal retinal endothelial cells upon Cre-mediated activation and predicted endothelial cell cycle status. We developed a semi-automated zonation program to define endothelial cell cycle status in spatially defined and developmentally distinct retinal areas and found predicted cell cycle stage differences in arteries, veins, and remodeled and angiogenic capillaries. Surprisingly, the predicted dearth of S-phase proliferative tip cells relative to stalk cells at the vascular front was accompanied by an unexpected enrichment for endothelial tip and stalk cells in G2, suggesting G2 stalling as a contribution to tip-cell arrest and dynamics at the front. Thus, this improved reporter precisely defines endothelial cell cycle status in vivo and reveals novel G2 regulation that may contribute to unique aspects of blood vessel network expansion.

The behavioral phenotype of children and adolescents with attenuated non-ketotic hyperglycinemia, intermediate to good subtype.

AIM: We aim to describe the behavioral phenotype of children and adolescents with the good to intermediate attenuated form of non-ketotic hyperglycinemia (NKH) and to explore associations between the behavioral phenotype and age, sex, plasma glycine levels and drug treatment. METHOD: Parents of children with attenuated NKH completed questionnaires assessing maladaptive behavior, adaptive behavior, social communication, speech/language development and motor development in addition to demographic and medical questions. RESULTS AND INTERPRETATION: Twelve children, age 6 to 21y, functioned at mild to severe intellectual disability levels. Their speech/language development was in line with their developmental quotient. Relative to their intellectual functioning, their motor development and communication were weaker in comparison to their general development. Their adaptive behavior, however, appeared a relative strength. There was no evidence for autism spectrum disorder occurring more frequently than expected, rather social skills, except for communication, were rated as a relative strength. Maladaptive behaviors with ADHD-like characteristics were present in more than two thirds of children. Maladaptive behaviors were significantly related to female sex and to taking dextromethorphan, but no significant relation between plasma glycine levels and behavior was found. Future studies will need to evaluate causality in the observed relation between dextromethorphan use and maladaptive behaviors. Clinicians should reconsider the benefit of dextromethorphan when presented with disruptive behaviors in children with attenuated NKH.

A Second-Generation Oral SARS-CoV-2 Main Protease Inhibitor Clinical Candidate for the Treatment of COVID-19.

Despite the record-breaking discovery, development and approval of vaccines and antiviral therapeutics such as Paxlovid, coronavirus disease 2019 (COVID-19) remained the fourth leading cause of death in the world and third highest in the United States in 2022. Here, we report the discovery and characterization of PF-07817883, a second-generation, orally bioavailable, SARS-CoV-2 main protease inhibitor with improved metabolic stability versus nirmatrelvir, the antiviral component of the ritonavir-boosted therapy Paxlovid. We demonstrate the in vitro pan-human coronavirus antiviral activity and off-target selectivity profile of PF-07817883. PF-07817883 also demonstrated oral efficacy in a mouse-adapted SARS-CoV-2 model at plasma concentrations equivalent to nirmatrelvir. The preclinical in vivo pharmacokinetics and metabolism studies in human matrices are suggestive of improved oral pharmacokinetics for PF-07817883 in humans, relative to nirmatrelvir. In vitro inhibition/induction studies against major human drug metabolizing enzymes/transporters suggest a low potential for perpetrator drug-drug interactions upon single-agent use of PF-07817883.

Efficient Gene Editing for Heart Disease via ELIP-Based CRISPR Delivery System.

Liposomes as carriers for CRISPR/Cas9 complexes represent an attractive approach for cardiovascular gene therapy. A critical barrier to this approach remains the efficient delivery of CRISPR-based genetic materials into cardiomyocytes. Echogenic liposomes (ELIP) containing a fluorescein isothiocyanate-labeled decoy oligodeoxynucleotide against nuclear factor kappa B (ELIP-NF-κB-FITC) were used both in vitro on mouse neonatal ventricular myocytes and in vivo on rat hearts to assess gene delivery efficacy with or without ultrasound. In vitro analysis was then repeated with ELIP containing Cas9-sg-IL1RL1 (interleukin 1 receptor-like 1) RNA to determine the efficiency of gene knockdown. ELIP-NF-κB-FITC without ultrasound showed limited gene delivery in vitro and in vivo, but ultrasound combined with ELIP notably improved penetration into heart cells and tissues. When ELIP was used to deliver Cas9-sg-IL1RL1 RNA, gene editing was successful and enhanced by ultrasound. This innovative approach shows promise for heart disease gene therapy using CRISPR technology.

Evidence for tactile 3D shape discrimination by octopus.

Octopuses integrate visual, chemical and tactile sensory information while foraging and feeding in complex marine habitats. The respective roles of these modes are of interest ecologically, neurobiologically, and for development of engineered soft robotic arms. While vision guides their foraging path, benthic octopuses primarily search "blindly" with their arms to find visually hidden prey amidst rocks, crevices and coral heads. Each octopus arm is lined with hundreds of suckers that possess a combination of chemo- and mechanoreceptors to distinguish prey. Contact chemoreception has been demonstrated in lab tests, but mechanotactile sensing is less well characterized. We designed a non-invasive live animal behavioral assay that isolated mechanosensory capabilities of Octopus bimaculoides arms and suckers to discriminate among five resin 3D-printed prey and non-prey shapes (all with identical chemical signatures). Each shape was introduced inside a rock dome and was only accessible to the octopus' arms. Octopuses' responses were variable. Young octopuses discriminated the crab prey shape from the control, whereas older octopuses did not. These experiments suggest that mechanotactile sensing of 3D shapes may aid in prey discrimination; however, (i) chemo-tactile information may be prioritized over mechanotactile information in prey discrimination, and (ii) mechanosensory capability may decline with age.

Antithrombotic Management and Outcomes of Anterior ST-Elevation Myocardial Infarction With New-Onset Wall Motion Abnormalities in Men and Women.

Background: In patients with anterior ST-elevation myocardial infarction (STEMI) and new-onset antero-apical wall motion abnormalities (WMAs), whether the rate of prophylaxis against left ventricular thrombus and outcomes differ between men and women is unknown. Methods: A multicentre retrospective cohort study of patients with STEMI and new-onset antero-apical WMAs treated with primary percutaneous coronary intervention was conducted. Patients with an established indication of oral anticoagulation (OAC) were excluded. The rates of triple therapy (double antiplatelet therapy + OAC) at discharge were compared for women vs men. The rates of net adverse clinical events, a composite of mortality, myocardial infarction, stroke or transient ischemic attack, systemic thromboembolism or Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding at 6 months were compared across sex using a multivariate logistic regression model. Results: A total of 1664 patients were included in the primary analysis, of whom 402 (24.2%) were women and 1262 (75.8%) were men. A total of 138 women (34.3%) and 489 men (38.7%) received a triple therapy prescription at discharge (P = 0.11). At 6 months, 33 women (8.2%) and 96 men (7.6%) experienced a net adverse clinical event (adjusted odds ratio 0.82; 95% confidence interval 0.49-1.37). No difference occurred in the risk of bleeding events and ischemic events between men and women, when these were analyzed separately. Conclusions: The rates of OAC prescription for left ventricular thrombus prophylaxis and clinical outcomes at 6 months were similar in women and men following anterior STEMI with new-onset antero-apical WMAs.

Contexte: On ignore si le taux de prophylaxie contre le thrombus ventriculaire gauche et les résultats thérapeutiques diffèrent entre les hommes et les femmes qui ont subi un infarctus du myocarde avec élévation du segment ST (STEMI) antérieur et ont des anomalies du mouvement pariétal (AMP) antéroapical d'apparition récente. Méthodes: Nous avons mené une étude de cohorte rétrospective multicentrique auprès de patients qui ont subi un STEMI et ont des AMP d'apparition récente traitées par une intervention coronarienne percutanée primaire. Nous avons exclu les patients chez lesquels il existait une indication établie à l'anticoagulation orale (ACO). Nous avons comparé les taux de trithérapie (bithérapie antiplaquettaire + ACO) à la sortie de l'hôpital entre les femmes et les hommes. Nous avons comparé les taux d'événements indésirables cliniques nets, le critère composite de mortalité, d'infarctus du myocarde, d'accident vasculaire cérébral ou d'accident ischémique transitoire, la thromboembolie systémique ou l'hémorragie de type 3 ou 5 selon le Bleeding Academic Research Consortium (BARC) après 6 mois entre les sexes au moyen du modèle de régression logistique multivariée. Résultats: Au sein des 1 664 patients de l'analyse principale, 402 (24,2 %) étaient des femmes et 1262 (75,8 %) étaient des hommes. Un total de 138 femmes (34,3 %) et de 489 hommes (38,7 %) ont reçu une ordonnance de trithérapie à la sortie de l'hôpital (P = 0,11). Après 6 mois, 33 femmes (8,2 %) et 96 hommes (7,6 %) ont subi un événement indésirable net (rapport de cotes ajusté 0,82 ; intervalle de confiance à 95 % 0,49-1,37). Aucune différence n'a été notée dans le risque d'événements hémorragiques et d'événements ischémiques entre les hommes et les femmes lorsque ces événements étaient analysés séparément. Conclusions: Les taux d'ordonnances d'ACO en prophylaxie du thrombus ventriculaire gauche et les résultats cliniques après 6 mois étaient similaires entre les femmes et les hommes à la suite du STEMI antérieur et des AMP antéroapicale d'apparition récente.

Restrictive vs Liberal Blood Transfusions for Patients With Acute Myocardial Infarction and Anemia by Heart Failure Status: An RCT Subgroup Analysis.

BACKGROUND: Red blood cell transfusion can cause fluid overload. We evaluated the interaction between heart failure (HF) at baseline and transfusion strategy on outcomes in acute myocardial infarction (AMI). METHODS: We used data from the randomized REALITY trial. HF was defined as history of HF or Killip class > 1 at randomization. Primary outcome was major adverse cardiovascular events (MACE): composite of all-cause death, nonrecurrent AMI, stroke, or emergency revascularization prompted by ischemia at 30 days. RESULTS: Among 658 randomized patients, 311 (47.3%) had HF. Patients with HF had higher rates of MACE at 30 days and 1 year and higher rates of nonfatal new-onset HF. There was no interaction between HF and effect of randomized assignment on the primary outcome or nonfatal new-onset HF. A liberal transfusion strategy was associated with increased all-cause death at 30 days and at 1 year in patients with HF (Pinteraction = 0.009 and P = 0.049, respectively). The main numerical difference in cause of death between restrictive and liberal strategies was death by HF at 30 days (4 vs 11). CONCLUSIONS: HF is frequent in patients with AMI and anemia and is associated with higher risk of MACE (including all-cause death) and nonfatal new-onset HF. Although there was no interaction of HF with effect of transfusion strategy on MACE, a liberal transfusion strategy was associated with higher all-cause death that appears driven by a higher risk of early death caused by HF. CLINICAL TRIAL REGISTRATION: NCT02648113.

Differential endothelial cell cycle status in postnatal retinal vessels revealed using a novel PIP-FUCCI reporter and zonation analysis.

Cell cycle regulation is critical to blood vessel formation and function, but how the endothelial cell cycle integrates with vascular regulation is not well-understood, and available dynamic cell cycle reporters do not precisely distinguish all cell cycle stage transitions in vivo. Here we characterized a recently developed improved cell cycle reporter (PIP-FUCCI) that precisely delineates S phase and the S/G2 transition. Live image analysis of primary endothelial cells revealed predicted temporal changes and well-defined stage transitions. A new inducible mouse cell cycle reporter allele was selectively expressed in postnatal retinal endothelial cells upon Cre-mediated activation and predicted endothelial cell cycle status. We developed a semi-automated zonation program to define endothelial cell cycle status in spatially defined and developmentally distinct retinal areas and found predicted cell cycle stage differences in arteries, veins, and remodeled and angiogenic capillaries. Surprisingly, the predicted dearth of proliferative tip cells at the vascular front was accompanied by an unexpected enrichment for endothelial tip cells in G2, suggesting G2 stalling as a contribution to tip-cell arrest. Thus, this improved reporter precisely defines endothelial cell cycle status in vivo and reveals novel G2 regulation that may contribute to unique aspects of blood vessel network expansion.

Seroprevalence of human adenovirus type 5 neutralizing antibodies in the Philippines.

Human adenovirus (HAdV), particularly the HAdV type 5 (HAdV-5), has been extensively utilized in the development of vector vaccines due to its high immunogenicity, good safety profile, and ease of propagation. However, one of the main challenges in its use is the presence of pre-existing immunity among vaccine recipients. Pre-existing neutralizing antibodies (NAbs) can prevent the uptake of HAdV-5 vectors and reduce vaccine efficacy. Hence, this study investigated the seroprevalence of NAbs against HAdV-5 in urban and rural regions of the Philippines. Luciferase-based neutralization assay was performed on 391 plasma/serum samples. Out of these samples, 346 or 88.5% were positive for HAdV-5 NAbs, and the majority of them (56.8%) had high titers against the virus. Among the regions included in this study, Bicol (Region V) had the highest seroprevalence rate (94.1%). Our findings show that a significant number of adults in the Philippines have pre-existing immunity against HAdV-5. This supports the recommendation that vaccination programs in the country should consider implementing vaccination techniques, such as a prime-boost regimen or addition of booster doses, to address the potential negative effects of pre-existing HAdV-5 immunity in the efficacy of adenoviral vector-based vaccines.

CHEX-seq detects single-cell genomic single-stranded DNA with catalytical potential.

Genomic DNA (gDNA) undergoes structural interconversion between single- and double-stranded states during transcription, DNA repair and replication, which is critical for cellular homeostasis. We describe "CHEX-seq" which identifies the single-stranded DNA (ssDNA) in situ in individual cells. CHEX-seq uses 3'-terminal blocked, light-activatable probes to prime the copying of ssDNA into complementary DNA that is sequenced, thereby reporting the genome-wide single-stranded chromatin landscape. CHEX-seq is benchmarked in human K562 cells, and its utilities are demonstrated in cultures of mouse and human brain cells as well as immunostained spatially localized neurons in brain sections. The amount of ssDNA is dynamically regulated in response to perturbation. CHEX-seq also identifies single-stranded regions of mitochondrial DNA in single cells. Surprisingly, CHEX-seq identifies single-stranded loci in mouse and human gDNA that catalyze porphyrin metalation in vitro, suggesting a catalytic activity for genomic ssDNA. We posit that endogenous DNA enzymatic activity is a function of genomic ssDNA.

Short report: Initial pilot of a brief career development program for autistic young adults.

BACKGROUND: Many autistic young adults may struggle to progress to further education or employment after high school, highlighting the need for tailored career development programs. If provided with the proper resources and support, the obstacles faced by autistic youth in pursuing post-secondary activities may decrease. AIMS: This pilot study aimed to examine the feasibility and preliminary efficacy of a brief career development program consisting of a strengths and challenges intervention paired with a 12-week workshop intervention. METHODS AND PROCEDURES: We studied the participants' changes in confidence and participation in pursuing post-secondary activities using a series of questionnaires in 20 participants, ages 16-23. The Myers-Briggs Type Indicator (MBTI) and Strong Interest Inventory (SII) helped the participants choose a post-secondary path. The 1-9 Vocational Index Scale measured post-secondary participation and hours working in a normed fashion. The Confidence Index Interval: Entering Workforce measured the participants' perceived confidence related to career transition. OUTCOMES AND RESULTS: Our results suggested that a brief career development program paired with a strengths and challenges intervention significantly increased post-secondary involvement in autistic young adults (N = 20, p = 0.014). There were no significant changes in confidence. CONCLUSIONS AND IMPLICATIONS: These findings provide proof of concept of a brief career development program using the MBTI and SII in young adults with ASD. WHAT THIS PAPER ADDS: Research in career development and transition for autistic young adults reveals that career interventions specific to the autistic population are lacking. Our pilot study explores a new type of intervention that incorporates the analysis of personal strengths and challenges with a 12-week transition workshop. Our project is the first to utilize the MBTI and SII as a tool to guide autistic youth in choosing a post-secondary path. The results of our study suggest that our program significantly improves post-secondary participation in autistic young adults. The findings provide proof of concept of using the MTBI and SII with a 12-week workshop for autistic young adults. At the end of our program, several participants began pursuing post-secondary education on track to obtain associate's (N = 8) or bachelor's (N = 3) degrees. Some began trade school (N = 3) and internships (N = 2), and others began employment or onboarding to employment (N = 4). Given the need for more evidence-based career interventions for autistic adults, our pilot study contributes significantly to autism research to better serve the autistic population.

Adipose transcriptome in the scalp of androgenetic alopecia.

Previous studies have shown how adipocytes can modulate the activity of hair follicle stem cells. However, the role of adipocytes in the pathogenesis of androgenetic alopecia (AGA) remains unknown. We aimed to determine signaling pathways related to the adipose tissue changes in the human scalp with AGA through RNA-seq analysis. RNA was isolated from the adipose tissues derived from the bald (frontal) and normal (occipital) scalps of male patients with AGA (n = 4). The pooled RNA extracts from these samples were subjected to RNA sequencing, followed by differential gene expression and pathway analysis. Our gene expression analysis identified 1,060 differentially expressed genes, including 522 upregulated and 538 downregulated genes in the bald AGA scalp. Biological pathways pertaining to either adipose tissue metabolism or the hair cycle were generated in our pathway analysis. Downregulation of the peroxisome proliferator-activated receptor (PPAR) signaling pathway was noted to be significant in the bald scalp. Expression of adipogenic markers (e.g., PPARG, FABP4, PLN1, and ADIPOQ) was also decreased in the bald site. These findings imply that adipogenesis becomes downregulated in AGA, specifically within the bald scalp adipose. Our results lead to the hypothesis that PPARγ-mediated adipogenesis in the scalp adipose, via crosstalk with signaling pathways involved in hair cycling, might play a role in AGA.

Quantitative non-nutritive sucking measurement as a predictor of oral feeding readiness in newborns.

Background and purpose: The purpose of this study is to examine the relationship between the parameters of a silver nanowire-based flexible pressure sensor developed to measure the non-nutritive sucking (NNS) performance and predict the nutritive sucking status in preterm infants. Methods: Preterm infants who were referred for feeding difficulty during the transition period from tubal feeding to oral feeding were enrolled in our study. A flexible pressure sensor was used to measure the non-nutritive sucking parameters of neonates. The evaluator stimulated the infants' lips and tongue with a pacifier integrated with a sucking pressure sensor, to check whether non-nutritive sucking had occurred. When the sucking reflex was induced, it was measured. The infants' sucking characteristics were subdivided into classifications according to the NOMAS criteria and full oral feeding (FOF) status. Quantitative NNS measurement according to the feeding state was compared between groups. Results: When comparing the quantitative NNS measurement by feeding characteristics, the average sucking pressure was significantly higher in infants in the FOF capable group than those in the incomplete FOF group. In addition, the maximum and average sucking pressure was significantly higher in infants with a normal sucking pattern compared to those with a disorganized sucking pattern. The average NNS pressure was divided over the range of 0-3 kPa and the same weight was assigned to each item. When the optimal cut-off value for the sensitivity and specificity of the average NNS pressure to estimate the FOF was set, a pressure of 1.5 kPa yielded the highest sensitivity (84.62%) and specificity (67.65%) on the receiver operating characteristic (ROC) curve. The area under the curve (AUC) was 0.786, and this result was statistically significant. Conclusions: This study presents a quantitative parameter for non-nutritive sucking in preterm infants with the use of a flexible pressure sensor. Results show possible quantitative indicators that can aid in predicting when preterm infants can transition to oral feeding and their prognosis. This will serve as a basis for future research on determining the feeding transition period of newborns with health conditions that affect oral feeding.

Effects of physical exercise, LEGO, and Minecraft activities on anxiety in underserved children with autism: Study design and methodological strategies.

Anxiety is a common comorbidity for individuals with ASD, and there is some preliminary data about the efficacy of physical exercise to alleviate anxiety. However, we are not aware of any studies that have compared the effects of a physical exercise program on anxiety in underserved children with ASD using a randomized controlled research design. This paper describes a method to evaluate and compare the efficacy of an 8-week physical exercise intervention with a sedentary play intervention to alleviate anxiety in young children with autism spectrum disorders (ASD) from underserved backgrounds. We assessed anxiety and its physical symptoms using the parent-rated Child Behavior Checklist DSM-5 anxiety (CBCL DSM-5) subscale, the child-rated Screen for Childhood Anxiety Related Emotional Disorder (SCARED), the parent-rated Child's Sleep Habits Questionnaire (CSHQ), and salivary cortisol. We also utilized the Physical Activity Questionnaire for Older Children (PAQ-C) to assess physical activity level and identify compounds. Unique components of this study include: •Implementation of novel physical exercise and sedentary play interventions that have been designed for children with ASD.•Recruitment of predominantly underserved and non-English speaking families.

Systematic Sampling of the Female Reproductive System for Molecular Characterization.

As part of the National Institutes of Health Human BioMolecular Atlas Program to develop a global platform to map the 37 trillion cells in the adult human body, we are generating a comprehensive molecular characterization of the female reproductive system. Data gathered from multiple single-cell/single-nucleus and spatial molecular assays will be used to build a 3D molecular atlas. Herein, we describe our multistep protocol, beginning with an optimized organ procurement workflow that maintains functional characteristics of the uterus, ovaries, and fallopian tubes by perfusing these organs with preservation solution. We have also developed a structured tissue sampling procedure that retains information on individual-level anatomic, physiologic, and individual diversity of the female reproductive system, toward full exploration of the function and structure of female reproductive cells. © 2023 Wiley Periodicals LLC. Basic Protocol 1: Preparation and preservation of the female reproductive system (ovaries, fallopian tubes, and uterus) prior to procurement Basic Protocol 2: Removal of the female reproductive system en bloc Basic Protocol 3: Postsurgical dissection of ovaries Basic Protocol 4: Postsurgical dissection of fallopian tubes Basic Protocol 5: Postsurgical dissection of cervix Basic Protocol 6: Postsurgical dissection of uterine body Support Protocol 1: OCT-embedded tissue protocol Support Protocol 2: Tissue fixation protocol Support Protocol 3: Snap-frozen tissue protocol Basic Protocol 7: Tissue slice preparation for Visium analysis Support Protocol 4: Hematoxylin and eosin staining for 10X Visium imaging Basic Protocol 8: Manual tissue dissociation for Multiome analysis Basic Protocol 9: Tissue dissociation for Multiome analysis using S2 Singulator.

Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Intravenous Infusions of PF-07304814 (Lufotrelvir) in Participants Hospitalized With COVID-19.

Background: An urgent need remains for antiviral therapies to treat patients hospitalized with COVID-19. PF-07304814-the prodrug (lufotrelvir) and its active moiety (PF-00835231)-is a potent inhibitor of the SARS-CoV-2 3CL protease. Method: Eligible participants were 18 to 79 years old and hospitalized with confirmed COVID-19. This first-in-human phase 1b study was designed with 2 groups: single ascending dose (SAD) and multiple ascending dose (MAD). Participants could receive local standard-of-care therapy. In SAD, participants were randomized to receive a 24-hour infusion of lufotrelvir/placebo. In MAD, participants were randomized to receive a 120-hour infusion of lufotrelvir/placebo. The primary endpoint was to assess the safety and tolerability of lufotrelvir. The secondary endpoint was to evaluate the pharmacokinetics of lufotrelvir and PF-00835231. Results: In SAD, participants were randomized to receive 250 mg lufotrelvir (n = 2), 500 mg lufotrelvir (n = 2), or placebo (n = 4) by continuous 24-hour infusion. In MAD, participants were randomized to receive 250 mg lufotrelvir (n = 7), 500 mg lufotrelvir (n = 6), or placebo (n = 4) by continuous 120-hour infusion. No adverse events or serious adverse events were considered related to lufotrelvir. At doses of 250 and 500 mg, concentrations for the prodrug lufotrelvir and active moiety PF-00835231 increased in a dose-related manner. Unbound concentrations of the lufotrelvir active metabolite reached steady state approximately 2- and 4-fold that of in vitro EC90 following 250- and 500-mg doses, respectively. Conclusions: These safety and pharmacokinetic findings support the continued evaluation of lufotrelvir in clinical studies. Clinical Trials Registration. ClinicalTrials.gov NCT04535167.

Clinical application of serum biomarkers for detecting and monitoring of chronic plaque psoriasis.

Psoriasis, a chronic, multisystemic inflammatory disease affecting millions of people globally, manifests as erythematous, thick, scaly plaques on the skin. Clinical evaluation remains to be the benchmark for diagnosis and monitoring of this debilitating disease. With current advancements in targeted molecular therapy for psoriasis such as biologics, molecular detection methods may also help guide clinical decisions and therapeutic strategies through quantification of circulating biomarkers, which could reflect the underlying pathogenic events happening at a certain point of the disease course. In this review, we will discuss how biomarkers are detected in serum samples using enzyme-linked immunosorbent assay (ELISA). This review will feature candidate biomarkers supported by clinical data for psoriasis including, but not limited to, cytokines, chemokines, adipokines, and antimicrobial peptides. A better understanding of the common method used for biomarker detection would enable physicians to interpret and correlate laboratory results with the disease pathogenesis and clinical outcomes, e.g., severity assessment and/or therapeutic response. With better health outcomes as the main goal, the utility of such information to evaluate and even predict treatment response would be a major step closer towards patient-tailored management.

A New Family of Layered Metal-Organic Semiconductors: Cu/V-Organophosphonates.

Herein, we report the design and synthesis of a layered redox-active, antiferromagnetic metal organic semiconductor crystals with the chemical formula [Cu(H2 O)2 V(µ-O)(PPA)2 ] (where PPA is phenylphosphonate). The crystal structure of [Cu(H2 O)2 V(µ-O)(PPA)2 ] shows that the metal phosphonate layers are separated by phenyl groups of the phenyl phosphonate linker. Tauc plotting of diffuse reflectance spectra indicates that [Cu(H2 O)2 V(µ-O)(PPA)2 ] has an indirect band gap of 2.19 eV. Photoluminescence (PL) spectra indicate a complex landscape of energy states with PL peaks at 1.8 and 2.2 eV. [Cu(H2 O)2 V(µ-O)(PPA)2 ] has estimated hybrid ionic and electronic conductivity values between 0.13 and 0.6 S m-1 . Temperature-dependent magnetization measurements show that [Cu(H2 O)2 V(µ-O)(PPA)2 ] exhibits short range antiferromagnetic order between Cu(II) and V(IV) ions. [Cu(H2 O)2 V(µ-O)(PPA)2 ] is also photoluminescent with photoluminescence quantum yield of 0.02%. [Cu(H2 O)2 V(µ-O)(PPA)2 ] shows high electrochemical, and thermal stability.