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Abstract There are few studies evaluating the effects of dairy waste application on sweet potato productivity, especially when combined with organic compost fertilization. In this context, the objective was to evaluate the effects of dairy waste fertilization, with or without organic compost, on the yield components and quality of sweet potato. The experiment was conducted under field conditions from April to August 2019 at the UFRPE experimental farm in Garanhuns, Pernambuco, using a randomized block design with different doses of dairy waste (0, 5, 10, and 15 m3 ha−1) in the presence and absence of organic compost, in addition to a control with mineral fertilization. The analyzed variables included ash and starch contents, total and marketable yield, as well as tuber quality parameters. For ash content in the absence of organic compost, the dose of maximum efficiency was 10.21 m3 ha−1, resulting in 0.55% ash, while the number of marketable tubers reached maximum efficiency at 8.05 m3 ha−1, providing 25.09 tubers per plot. The application of dairy waste, either alone or combined with organic compost, promoted increases in sweet potato yield (t ha−1) and quality, showing performance comparable to mineral fertilizer. The highest ash and starch contents were obtained with the exclusive use of dairy waste, highlighting its potential as a sustainable fertilization alternative. Resumo São escassos estudos que avaliam os efeitos da aplicação de resíduos de laticínio sobre a produtividade da batata-doce, sobretudo quando associados à adubação com composto orgânico. Nesse contexto, objetivou-se avaliar os efeitos da adubação com resíduos de laticínio associados ou não ao composto orgânico nos componentes de rendimento e qualidade da batata-doce. O experimento foi conduzido em campo, de Abril a Agosto de 2019, na fazenda experimental da UFRPE em Garanhuns-PE, utilizando um delineamento em blocos casualizados, com diferentes doses de resíduo de laticínio (0, 5, 10 e 15 m3 ha−1) na presença e ausência de composto orgânico, além de uma testemunha com fertilização mineral. As variáveis analisadas incluíram teores de cinzas e amido, produtividade total e comercial, além de parâmetros de qualidade das túberas. Para os teores cinzas na ausência do composto orgânico, a dose de máxima eficiência foi de 10,21 m3 ha-1, proporcionando 0,55% de cinzas, o número de tubérculos comerciais teve dose de máxima eficiência de 8,05 m3 ha-1 proporcionando 25,09 tubérculos por parcela. A aplicação de resíduos de laticínio, isolados ou combinados ao composto orgânico, promoveu aumento na produtividade (t ha-1) e qualidade da batata-doce, apresentando desempenho semelhante ao fertilizante mineral. Os maiores teores de cinza e amido foram obtidos com o uso exclusivo do resíduo de laticínio, evidenciando seu potencial como alternativa sustentável de adubação.

Background: Severe neurological involvement in systemic lupus erythematosus (NPSLE) is one of the most dreadful complications of the disease. Objective: To identify the best drug, dose, and treatment. Patients and methods: The study was a controlled clinical trial at two tertiary care centres of patients with SLE according to the ACR criteria, with incident (no more than 15 days) onset of severe NP manifestations such as seizures, optic neuritis, peripheral or cranial neuropathy, coma, brainstem disease, or transverse myelitis. Induction treatment with 3 g of IV methylprednisolone (MP) followed by either IV monthly cyclophosphamide (Cy) versus IV MP bimonthly every 4 months for 1 year and then IV Cy or IV MP every 3 months for another year. The primary end point was response to treatment: at least 20% improvement from basal conditions on clinical, laboratory, or specific neurological testing variables. Results: Overall, a response rate of 75% was observed. Of the 32 patients studied, 18/19 receiving Cy and 7/13 receiving MP responded to treatment (p<0.03). Conclusions: Cy seems to be more effective than MP in the treatment of acute, severe NPSLE.

Knee osteoarthritis (OA) is a leading cause of pain and disability. Although conventional treatments show modest benefits, pilot and phase I/II trials with bone marrow (BM) and adipose‐derived (AD) mesenchymal stromal cells (MSCs) point to the feasibility, safety, and occurrence of clinical and structural improvement in focal or diffuse disease. This study aimed to assess the safety and efficacy of the intra‐articular injection of single or repeated umbilical cord‐derived (UC) MSCs in knee OA. UC‐MSCs were cultured in an International Organization for Standardization 9001:2015 certified Good Manufacturing Practice‐type Laboratory. Patients with symptomatic knee OA were randomized to receive hyaluronic acid at baseline and 6 months (HA, n = 8), single‐dose (20 × 106) UC‐MSC at baseline (MSC‐1, n = 9), or repeated UC‐MSC doses at baseline and 6 months (20 × 106 × 2; MSC‐2, n = 9). Clinical scores and magnetic resonance images (MRIs) were assessed throughout the 12 months follow‐up. No severe adverse events were reported. Only MSC‐treated patients experienced significant pain and function improvements from baseline (p = .001). At 12 months, Western Ontario and Mc Master Universities Arthritis Index (WOMAC‐A; pain subscale) reached significantly lower levels of pain in the MSC‐2‐treated group (1.1 ± 1.3) as compared with the HA group (4.3 ± 3.5; p = .04). Pain Visual Analog scale was significantly lower in the MSC‐2 group versus the HA group (2.4 ± 2.1 vs. 22.1 ± 9.8, p = .03) at 12 months. For total WOMAC, MSC‐2 had lower scores than HA at 12 months (4.2 ± 3.9 vs. 15.2 ± 11, p = .05). No differences in MRI scores were detected. In a phase I/II trial (NCT02580695), repeated UC‐MSC treatment is safe and superior to active comparator in knee OA at 1‐year follow‐up. Stem Cells Translational Medicine 2019;8:215&224

Alzheimer's disease and related dementias (ADRD) are among the top contributors to disability and mortality in later life. As with many chronic conditions, aging is the single most influential factor in the development of ADRD. Even among older adults who remain free of dementia throughout their lives, cognitive decline and neurodegenerative changes are appreciable with advancing age, suggesting shared pathophysiological mechanisms. In this Review, we provide an overview of changes in cognition, brain morphology, and neuropathological protein accumulation across the lifespan in humans, with complementary and mechanistic evidence from animal models. Next, we highlight selected aging processes that are differentially regulated in neurodegenerative disease, including aberrant autophagy, mitochondrial dysfunction, cellular senescence, epigenetic changes, cerebrovascular dysfunction, inflammation, and lipid dysregulation. We summarize research across clinical and translational studies to link biological aging processes to underlying ADRD pathogenesis. Targeting fundamental processes underlying biological aging may represent a yet relatively unexplored avenue to attenuate both age-related cognitive decline and ADRD. Collaboration across the fields of geroscience and neuroscience, coupled with the development of new translational animal models that more closely align with human disease processes, is necessary to advance novel therapeutic discovery in this realm.

Microneedle patches are a promising source for transdermal diffusion of macromolecules and are designed to painlessly penetrate the skin. In this study, a biodegradable chitosan microneedle patch to deliver meloxicam for managing pain in cattle was tested. The potential of reuse of the polymeric solution to fabricate the patches, optimization of fabrication, morphological analysis of the microneedle patch and analysis of preservation of the chemical composition after sterilization were evaluated. In-vitro analysis consisted of studying in-vitro penetration mechanical properties, compression testing analysis of microneedle patch, and in-vitro drug release analysis. In-vivo studies were performed to analyze the dissolution capability of the microneedle patch. Results regarding the physical characteristics, chemical composition, and mechanical properties confirmed that rheological properties of the chitosan solution, present significant differences over time, demonstrating that reusing the solution on the fourth day results in failure patches. Morphological characteristics and chemical composition studies revealed that the process of sterilization (ethylene oxide gas) needed for implanting the patches into the skin did not affect the properties of microneedle patches. In-vitro studies showed that approximately 33.02 ± 3.88% of the meloxicam was released over 7 days. A full penetration of the microneedles into the skin can be obtained by applying approximately 3.2 N. In-vivo studies demonstrated that microneedle patches were capable of swelling and dissolving, exhibiting a dissolution percentage of more than 50% of the original height of microneedle after 7 days. No abnormal tissue, swelling, or inflammation was observed in the implanted area. The results of this work show that chitosan biodegradable microneedle patches may be useful to deliver meloxicam to improve pain management of cattle with positive effects for commercial manufacturing.

During its two-year prime mission, the Transiting Exoplanet Survey Satellite (TESS) will perform a time-series photometric survey covering over 80% of the sky. This survey comprises observations of 26 24° × 96° sectors that are each monitored continuously for approximately 27 days. The main goal of TESS is to find transiting planets around 200,000 pre-selected stars for which fixed aperture photometry is recorded every two minutes. However, TESS is also recording and delivering full-frame images (FFIs) of each detector at a 30-minutes cadence. We have created an open-source tool, eleanor, to produce light curves for objects in the TESS FFIs. Here, we describe the methods used in eleanor to produce light curves that are optimized for planet searches. The tool performs background subtraction; aperture and point-spread function photometry; decorrelation of instrument systematics; and cotrending using principal component analysis. We recover known transiting exoplanets in the FFIs to validate the pipeline and perform a limited search for new planet candidates in Sector 1. Our tests indicate that eleanor produces light curves with significantly less scatter than other tools that have been used in the literature. Cadence-stacked images, and raw and detrended eleanor light curves for each analyzed star will be hosted on Mikulski Archive for Space Telescopes, with planet candidates on ExoFOP-TESS as Community TESS Objects of Interest. This work confirms the promise that the TESS FFIs will enable the detection of thousands of new exoplanets and a broad range of time domain astrophysics.

Purpose Three genetic conditions—hereditary breast and ovarian cancer syndrome, Lynch syndrome, and familial hypercholesterolemia—have tier 1 evidence for interventions that reduce morbidity and mortality, prompting proposals to screen unselected populations for these conditions. We examined the impact of genomic screening on risk management and early detection in an unselected population. Methods Observational study of electronic health records (EHR) among individuals in whom a pathogenic/likely pathogenic variant in a tier 1 gene was discovered through Geisinger’s MyCode project. EHR of all eligible participants was evaluated for a prior genetic diagnosis and, among participants without such a diagnosis, relevant personal/family history, postdisclosure clinical diagnoses, and postdisclosure risk management. Results Eighty-seven percent of participants (305/351) did not have a prior genetic diagnosis of their tier 1 result. Of these, 65% had EHR evidence of relevant personal and/or family history of disease. Of 255 individuals eligible to have risk management, 70% ( n  = 179) had a recommended risk management procedure after results disclosure. Thirteen percent of participants (41/305) received a relevant clinical diagnosis after results disclosure. Conclusion Genomic screening programs can identify previously unrecognized individuals at increased risk of cancer and heart disease and facilitate risk management and early cancer detection.

Quantum collisions Ultracold polar molecules offer the possibility of exploring quantum gases with inter-particle interactions that are strong, long-range and spatially anisotropic. Here, Ni et al . report the experimental observation of dipolar collisions in an ultracold gas of fermionic 40 K 87 Rb molecules. For modest values of an applied electric field, they observe a dramatic increase in the loss rate due to ultracold chemical reactions. Ultracold polar molecules offer the possibility of exploring quantum gases with interparticle interactions that are strong, long-range and spatially anisotropic. Here, dipolar collisions in an ultracold gas of fermionic potassium–rubidium molecules have been experimentally observed. The results show how the long-range dipolar interaction can be used for electric-field control of chemical reaction rates in an ultracold gas of polar molecules. Ultracold polar molecules offer the possibility of exploring quantum gases with interparticle interactions that are strong, long-range and spatially anisotropic. This is in stark contrast to the much studied dilute gases of ultracold atoms, which have isotropic and extremely short-range (or ‘contact’) interactions. Furthermore, the large electric dipole moment of polar molecules can be tuned using an external electric field; this has a range of applications such as the control of ultracold chemical reactions 1 , the design of a platform for quantum information processing 2 , 3 , 4 and the realization of novel quantum many-body systems 5 , 6 , 7 , 8 . Despite intense experimental efforts aimed at observing the influence of dipoles on ultracold molecules 9 , only recently have sufficiently high densities been achieved 10 . Here we report the experimental observation of dipolar collisions in an ultracold molecular gas prepared close to quantum degeneracy. For modest values of an applied electric field, we observe a pronounced increase in the loss rate of fermionic potassium–rubidium molecules due to ultracold chemical reactions. We find that the loss rate has a steep power-law dependence on the induced electric dipole moment, and we show that this dependence can be understood in a relatively simple model based on quantum threshold laws for the scattering of fermionic polar molecules. In addition, we directly observe the spatial anisotropy of the dipolar interaction through measurements of the thermodynamics of the dipolar gas. These results demonstrate how the long-range dipolar interaction can be used for electric-field control of chemical reaction rates in an ultracold gas of polar molecules. Furthermore, the large loss rates in an applied electric field suggest that creating a long-lived ensemble of ultracold polar molecules may require confinement in a two-dimensional trap geometry to suppress the influence of the attractive, ‘head-to-tail’, dipolar interactions 11 , 12 , 13 , 14 .

Human papillomaviruses (HPVs) maintain their genomes as minichromosomes in the nuclei of infected keratinocytes. This study investigates the association of HPV31 genomes with host chromatin using both HiC and 4C-seq chromosome conformation capture techniques. We show that HPV31 genomes preferentially associate with transcriptionally active A compartments of host chromatin, regions of open chromatin defined by ATAC-seq, and super-enhancers defined by Brd4 and H3K27ac ChIP-seq. The viral genome association sites were also highly correlated with genomic loci previously identified as common HPV integration sites in cervical cancers. Recent studies have shown that transcriptionally active sites are prone to dsDNA breaks, and we find a strong correlation among dsBREAK datasets with transcriptionally active and open regions of host chromatin and the HPV31 genome association sites defined in our study. These findings suggest that HPV genomes associate with cellular transcriptional epicenters to maintain active viral gene expression during persistent infection, but also indicate that the susceptibility of these regions to dsDNA breaks could explain their propensity for viral DNA integration in HPV-associated cancers.

The development of a portfolio of COVID-19 vaccines to vaccinate the global population remains an urgent public health imperative 1 . Here we demonstrate the capacity of a subunit vaccine, comprising the SARS-CoV-2 spike protein receptor-binding domain displayed on an I53-50 protein nanoparticle scaffold (hereafter designated RBD–NP), to stimulate robust and durable neutralizing-antibody responses and protection against SARS-CoV-2 in rhesus macaques. We evaluated five adjuvants including Essai O/W 1849101, a squalene-in-water emulsion; AS03, an α-tocopherol-containing oil-in-water emulsion; AS37, a Toll-like receptor 7 (TLR7) agonist adsorbed to alum; CpG1018-alum, a TLR9 agonist formulated in alum; and alum. RBD–NP immunization with AS03, CpG1018-alum, AS37 or alum induced substantial neutralizing-antibody and CD4 T cell responses, and conferred protection against SARS-CoV-2 infection in the pharynges, nares and bronchoalveolar lavage. The neutralizing-antibody response to live virus was maintained up to 180 days after vaccination with RBD–NP in AS03 (RBD–NP-AS03), and correlated with protection from infection. RBD–NP immunization cross-neutralized the B.1.1.7 SARS-CoV-2 variant efficiently but showed a reduced response against the B.1.351 variant. RBD–NP-AS03 produced a 4.5-fold reduction in neutralization of B.1.351 whereas the group immunized with RBD–NP-AS37 produced a 16-fold reduction in neutralization of B.1.351, suggesting differences in the breadth of the neutralizing-antibody response induced by these adjuvants. Furthermore, RBD–NP-AS03 was as immunogenic as a prefusion-stabilized spike immunogen (HexaPro) with AS03 adjuvant. These data highlight the efficacy of the adjuvanted RBD–NP vaccine in promoting protective immunity against SARS-CoV-2 and have led to phase I/II clinical trials of this vaccine (NCT04742738 and NCT04750343). Trials in rhesus macaques show that a subunit vaccine against SARS-CoV-2, comprising the spike protein receptor-binding domain displayed on a nanoparticle protein scaffold, produces a robust protective response against the virus.