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In a phase 3 trial involving more than 15,000 participants, two doses of NVX-CoV2373, a recombinant SARS-CoV-2 nanoparticle vaccine, administered 21 days apart had a vaccine efficacy of 89.7%. Reactogenicity was generally mild and transient, and adverse events were infrequent and of low grade.

High failure rates of femoropopliteal artery reconstruction are commonly attributed to complex 3D arterial deformations that occur with limb movement. The purpose of this study was to develop a method for accurate assessment of these deformations. Custom-made stainless-steel markers were deployed into 5 in situ cadaveric femoropopliteal arteries using fluoroscopy. Thin-section CT images were acquired with each limb in the straight and acutely bent states. Image segmentation and 3D reconstruction allowed comparison of the relative locations of each intra-arterial marker position for determination of the artery’s bending, torsion and axial compression. After imaging, each artery was excised for histological analysis using Verhoeff–Van Gieson staining. Femoropopliteal arteries deformed non-uniformly with highly localized deformations in the proximal superficial femoral artery, and between the adductor hiatus and distal popliteal artery. The largest bending (11±3–6±1mm radius of curvature), twisting (28±9–77±27°/cm) and axial compression (19±10–30±8%) were registered at the adductor hiatus and the below knee popliteal artery. These deformations were 3.7, 19 and 2.5 fold more severe than values currently reported in the literature. Histology demonstrated a distinct sub-adventitial layer of longitudinally oriented elastin fibers with intimal thickening in the segments with the largest deformations. This endovascular intra-arterial marker technique can quantify the non-uniform 3D deformations of the femoropopliteal artery during knee flexion without disturbing surrounding structures. We demonstrate that 3D arterial bending, torsion and compression in the flexed lower limb are highly localized and are substantially more severe than previously reported.

Background Alzheimer’s disease is characterized by the deposition of amyloid-beta (Aβ) plaques, necessitating early detection and reliable biomarkers for effective intervention. Non-human primates, particularly aged vervet monkeys, offer valuable models for studying age-related Aβ pathology due to their close phylogenetic relationship to humans and similar neuropathological features. Methods This study assessed the utility of [ 18 F]FC119S, a novel Aβ-targeting PET radiotracer, in aged vervet monkeys. The radiochemistry of [ 18 F]FC119S was optimized and automated to ensure high radiochemical purity and molar activity. PET/MRI imaging was performed to evaluate tracer uptake, distribution, and washout kinetics. Correlations between [ 18 F]FC119S uptake and cerebrospinal fluid (CSF) and plasma biomarkers—including Aβ 42/40 ratio, pTau181, neurofilament light chain (NfL), and pTau181/Aβ 42 ratio—were analyzed. Autoradiography was conducted to validate regional tracer binding in brain tissues. Results [ 18 F]FC119S demonstrated high brain uptake, rapid washout, and widespread cortical distribution in vervet monkeys, mirroring patterns observed in human studies. Tracer uptake showed negative associations with CSF Aβ 42/40 ratio in Aβ-affected regions, and significant positive correlations with CSF pTau181 and CSF pTau181/Aβ 42 ratio in the temporal lobe. Additionally, significant positive correlations were observed between [ 18 F]FC119S uptake and CSF NfL in the anterior cingulate gyrus, parietal, and occipital lobes. Autoradiography confirmed elevated tracer binding in specific brain regions of older vervets with low CSF Aβ 42 compared to younger counterparts. Conclusions These findings validate [ 18 F]FC119S as a promising PET radiotracer for tracking Aβ deposition in aged vervet monkeys. Its imaging characteristics and biomarker correlations support its translational potential for Alzheimer’s disease research and early diagnostic applications.

Background In humans, age‐related accumulations of physical deficits are often characterized by frailty indices, which predict increased risk for neurodegeneration characteristic of Alzheimer's disease (AD). However, social capabilities also may diminish, with considerable variation in inter‐individual trajectories of decline and AD risk. Social frailty has recently been proposed in humans and mice to characterize the severity of social impairments with age; however, no index of social frailty exists for nonhuman primates (NHPs). This represents a significant gap in the literature, as NHPs provide important translational opportunities to study brain‐body relationships that promote healthy versus pathological aging. Method Here, we developed a novel index of social frailty in female vervet monkeys (Chlorocebus aethiops sabaeus) using six components of social behavior measuring positive interactions, agonistic interactions and social isolation. Members of this study comprise the Wake Forest Aging Vervet Cohort, which includes 30+ captive females ranging from middle‐ to very old age (8‐29 years). Subjects live with their families in large, multi‐matrilineal social groups. We first tested whether social frailty in vervets recapitulated age‐related changes observed in humans. Next, we determined the cross‐sectional relationships between social frailty and neuroanatomy derived from structural MRI. Finally, we tested whether social frailty predicted biomarkers associated with AD (MesoScale Discovery Platform: Ab40, Ab42, Ab42:40, ptau181, NfL, and GFAP) in CSF at approximately one year follow‐up. Result The social frailty index increased with age (t= 3.695, p <0.001). Social frailty was positively associated with CSF volumes (t= 2.163 p = 0.035) and negatively associated with cortical gray matter (t=‐4.261, p <0.001), white matter (t=‐2.591, p = 0.013), and cerebellar (t=‐3.716, p <0.001) volumes. Social frailty also predicted several CSF biomarkers associated with AD. Higer social frailty predicted higher levels of phosphorylated tau (t=2.304, p = 0.024) but lower Ab42 (t=‐2.345 p = 0.022) and Ab40 (t=‐2.138, p = 0.036). Social frailty was also associated with elevated NfL and GFAP in CSF; however, the associations did not reach statistical significance (p's <0.10). Conclusion Like humans, some vervets may exhibit increasing socially frailty with age. These unhealthy aging trajectories ‐ characterized by fewer positive interactions, social isolation, and agonistic interactions ‐ are associated with AD neuroimaging and biofluid biomarkers.

Phytophthora infestans is the most destructive pathogen of potato and a model organism for the oomycetes, a distinct lineage of fungus-like eukaryotes that are related to organisms such as brown algae and diatoms. As the agent of the Irish potato famine in the mid-nineteenth century, P. infestans has had a tremendous effect on human history, resulting in famine and population displacement. To this day, it affects world agriculture by causing the most destructive disease of potato, the fourth largest food crop and a critical alternative to the major cereal crops for feeding the world's population. Current annual worldwide potato crop losses due to late blight are conservatively estimated at $6.7 billion. Management of this devastating pathogen is challenged by its remarkable speed of adaptation to control strategies such as genetically resistant cultivars. Here we report the sequence of the P. infestans genome, which at approximately 240 megabases (Mb) is by far the largest and most complex genome sequenced so far in the chromalveolates. Its expansion results from a proliferation of repetitive DNA accounting for approximately 74% of the genome. Comparison with two other Phytophthora genomes showed rapid turnover and extensive expansion of specific families of secreted disease effector proteins, including many genes that are induced during infection or are predicted to have activities that alter host physiology. These fast-evolving effector genes are localized to highly dynamic and expanded regions of the P. infestans genome. This probably plays a crucial part in the rapid adaptability of the pathogen to host plants and underpins its evolutionary potential.

Background Adjuvant chemoradiotherapy improved survival in patients with resected gastric adenocarcinoma in the Southwest Oncology Group/Intergroup 0116 trial. Our objective was to examine the impact of adjuvant treatment on overall survival (OS) in the general population. Methods Patients 18–85 years old who had undergone resection of non-metastatic gastric adenocarcinoma between May 2000 and December 2003, were identified from the Surveillance Epidemiology and End Results (SEER) database. Patients who had received pre-operative irradiation, had unknown stage or radiation status, or had a survival of 3 months or less from the date of diagnosis were excluded. Survival of those who received post-operative irradiation was compared with those who did not; Kaplan-Meier methods and Cox proportional hazards models were used. Results Of 4,041 patients, there was improved survival for those receiving adjuvant irradiation for stages III and IVM0, with a median OS of 31 versus 24 months ( P  = 0.005) and 20 versus 15 months ( P  < 0.001), respectively, and a trend for improved survival in univariate analysis of stage II ( P  = 0.0535). In final adjusted analysis, adjuvant irradiation significantly improved OS in stages III (HR: 0.71, P  = 0.0007) and IVM0 (HR: 0.66, P  < 0.0001). Adjusted analysis using a propensity score suggested that the benefit of adjuvant irradiation was similar in stage-II and -III patients. However, there was no statistical improvement in survival for stage-Ib and -II patients who had received adjuvant irradiation. Conclusions In this population-based analysis, adjuvant radiotherapy for stage-III and IVM0 gastric cancer significantly improved OS. Analysis of stage-Ib and -II patients is limited by small numbers, but there may not be the same benefit.

Abstract Objective: To assess the efficacy of long term octreotide as adjuvant treatment to programmed endoscopic sclerotherapy after acute variceal haemorrhage in cirrhotic portal hypertension. Design: Randomised clinical trial. Setting: University hospital. Subjects: 32 patients with cirrhotic portal hypertension. Interventions: Programmed injection sclerotherapy with subcutaneous octreotide 50 μg twice daily for 6 months, or programmed injection sclerotherapy alone. Main outcome measures: Episodes of recurrent variceal bleeding and survival. Results: Significantly fewer patients receiving combined octreotide and sclerotherapy had episodes of recurrent variceal bleeding compared with patients given sclerotherapy alone (1/16 v 7/16; P=0.037, Fisher's exact test), and their survival was significantly improved (P<0.02, log rank test); this improvement was maintained for 12 months after the end of the study. Combined treatment also resulted in a sustained decrease in portal pressure (median decrease −6.0 mm Hg, interquartile range −10 to −4.75 mm Hg, P=0.0002) compared with sclerotherapy alone (median increase 1.5 mm Hg, interquartile range 0.25 to 3.25 mm Hg), as well as a significant improvement in liver function as assessed by plasma concentrations of bilirubin, albumin, and alanine aminotransferase and by hepatocyte metabolism of aminopyrine labelled with carbon-14. Conclusion: Long term octreotide may be a valuable adjuvant to endoscopic sclerotherapy for acute variceal haemorrhage in cirrhotic portal hypertension. Key messages The long term use of vasoactive drugs as adjuvant treatment after endoscopic sclerotherapy or ligation for acute variceal haemorrhage has been suggested to reduce the risk of variceal rebleeding This randomised trial found that the addition of long term octreotide to endoscopic treatment reduced the rate of recurrent variceal haemorrhage in patients with cirrhotic portal hypertension Octreotide also improved survival after acute variceal haemorrhage in such patients Long term administration of somatostatin analogues offers a promising treatment to prevent recurrent variceal haemorrhage