Crimean-Congo haemorrhagic fever (CCHF) is an emerging tick-borne human disease in Spain. Understanding the spatiotemporal dynamics and exposure risk determinants of CCHF virus (CCHFV) in animal models is essential to predict the time and areas of highest transmission risk. With this goal, we designed a longitudinal survey in two wild ungulate species, the red deer ( Cervus elaphus) and the Eurasian wild boar ( Sus scrofa), in Doñana National Park, a protected Mediterranean biodiversity hotspot with high ungulate and CCHFV vector abundance, and which is also one of the main stopover sites for migratory birds between Africa and western Europe. Both ungulates are hosts to the main CCHFV vector in Spain, Hyalomma lusitanicum. We sampled wild ungulates annually from 2005 to 2020 and analysed the frequency of exposure to CCHFV by a double-antigen ELISA. The annual exposure risk was modelled as a function of environmental traits in an approach to understand exposure risk determinants that allow us to predict the most likely places and years for CCHFV transmission. The main findings show that H. lusitanicum abundance is a major driver of the fine-scale spatial CCHFV transmission risk, while inter-annual variations in the risk are conditioned by virus/vector hosts, by host community structure and by weather variations. The most relevant conclusion of the study is that the emergence of CCHF in Spain might have been associated with recent wild ungulate population changes promoting higher vector abundance. Decreasing wild ungulate population densities could reduce vector abundance and thus virus prevalence and the risk of CCHFV transmission to humans.

Lake has an important role of Earth’s hydrologic cycle. The changing of lake water area shows the ecological health of lakes by instant feedback. Most analyses of long-term monitoring of lake area are not comprehensive enough, This study based on the remote sensing images from 1977 to 2021, combined with the Keyhole satellite data, hydrographic survey, meteorology monitoring and land use change survey, investigated the Poyang lake water area changes. Moreover, examined the response relationship between lake water area and the impact factor, analyzed the influence of river lake interaction on lake water area.The results showed that: (1) From 1977 to 2017, the water area of Poyang Lake in flood season (June to September) and dry season (November to Next February) showed a significant downward trend by years. (2) In flood season, runoff, sediment, precipitation has significant correlation with water area. In dry season, sediment showed a significant correlation with water area. (3) The Three Gorges Dam water impoundment at the upper reaches of the Yangtze River weakened eliminated the blocking or reversing flow from the Yangtze River, caused the water area decreased in advance at the end of flood season after 2005, and decreased rapidly in dry season after 2003. (4) The change of lakebed elevation caused by sedimentation and human activities also accelerated the shrinkage of water area. Result demonstrated that the variation of river lake interaction is the primary cause of Poyang Lake water area dramatic change.

While most deep learning approaches are developed for single images, in real world applications, images are often obtained as a series to inform decision making. Due to hardware (memory) and software (algorithm) limitations, few methods have been developed to integrate multiple images so far. In this study, we present an approach that seamlessly integrates deep learning and traditional machine learning models, to study multiple images and score joint damages in rheumatoid arthritis. This method allows the quantification of joining space narrowing to approach the clinical upper limit. Beyond predictive performance, we integrate the multilevel interconnections across joints and damage types into the machine learning model and reveal the cross-regulation map of joint damages in rheumatoid arthritis. Corresponding author(s) Email:   hyangl@umich.edu or gyuanfan@umich.edu

Granular materials exhibit unique secondary flow behaviors upon shearing. We demonstrate, using particle dynamics simulations, that the secondary flow patterns are controlled by a pressure exerted on the particle bed. The threshold pressure, at which vortex flow transitions to disturbed or chaotic flow, depends on particle shape, that influences interparticle contacts and rheological performance. Our results show that the flow patterns are essentially determined by a dimensionless term combining the pressure and granular temperature for all the spherical and Platonic particles explored. Particle mixing is promoted by the vortex flow or the disturbed flow with strong diffusion. The highest mixing rate under a specified pressure is obtained for cubic particles, due to the remarkable microstructural ordering near the boundaries causing a high gradient of packing density. These findings may shed light on optimal control of granular secondary flows and mixing by tuning the applied pressure and particle shape.

While decomposition techniques in mathematical programming are usually designed for numerical efficiency, coordination problems within enterprise-wide optimization are often limited by organizational rather than numerical considerations. We propose a ‘data-driven’ coordination framework which manages to recover the same optimum as the equivalent centralized formulation while allowing coordinating agents to retain autonomy, privacy, and flexibility over their own objectives, constraints, and variables. This approach updates the coordinated, or shared, variables based on derivative-free optimization (DFO) using only coordinated variables to agent-level optimal subproblem evaluation ‘data’. We compare the performance of our framework using different DFO solvers (CUATRO, Py-BOBYQA, DIRECT-L, GPyOpt) against conventional distributed optimization (ADMM) on three case studies: collaborative learning, facility location, and multi-objective blending. We show that in low-dimensional and nonconvex subproblems, the exploration-exploitation trade-offs of DFO solvers can be leveraged to converge faster and to a better solution than in distributed optimization

A document by chenyu chu. Click on the document to view its contents.

Scientists ought to apply universally accepted definitions to technical terms to enable precise communication and discussion. Throughout history, many definitions have shifted, such as those of important terms in evolutionary biology, modes of life, and the nature of interactions. Conversely, throughout history, important terms have been used without proper definition. Two such terms are parasites and pathogens. An extensive body of literature considers parasites and pathogens to be categorically negative, which has resulted in definitions that lack objectivity and limit a full understanding of the biology of these organisms. Different interpretations have resulted in shifting definitions, in turn causing confusion. Here, we present the remarkable history of both definitions, an overview of alternative definitions put forward throughout history, and a working definition for both terms. We find that the line between what is a parasite or a pathogen is often blurry, and is additionally complicated due to the multi-modal nature of interactions.

Our review want to identify most incident risk factors that determine the persistence of PGP at 3-6 months after childbirth in women with PPGP or PPGP and PLBP, because of about 1/3 does not recover after childbirth and continues to experience symptoms after three months and in some cases up to two years. The research was performed on the databases ofMedline, Cochrane, Pedro, Scopus, Web of Science and Chinal from December 2018 to January 2022 following the indications of the PRISMA statement 2009 - and updated according to the PRISMA 2020- including observational cohort studies and prospective questionnaires in English. Two authors independently selected studies excluding specific, traumatic, gynecological / urological cause PGP or isolated PLBP and studies that did not include the primary outcome (presence / absence of PGP); studies with an initial assessment in pregnancy / within one month of delivery and with at least a follow-up at least 3 months after delivery were included. Two independent authors then performed an evaluation of the ROB using the QUIPS tool. Finally, in-depth qualitative analysis was conducted, since due to high degree of heterogeneity in the data collection of the included studies and lack of raw data suitable for quantitative analysis, it was not possible to carry out the originally assumed meta-analyzes for subgroups. High levels of pain in pregnancy, high number of positive provocative tests, history of LBP / LPP, high levels of disability in pregnancy, neurosis and high levels of Fear Avoidance Belief are main predictors of PPGP.

Objectives To summarise current practices in the diagnosis and management of Deep Neck Space Infections (DNSIs) To inform future studies in developing a framework in the management of DNSIs Design This review was registered on PROSPERO (CRD42021226449) and reported in line with PRISMA guidelines. All studies from 2000 that reported the investigation or management of DNSI were included. The search was limited to English language only. Databases searched included AMED, Embase, Medline and HMIC. Quantitative analysis was undertaken with descriptive statistics and frequency synthesis with 2 independent reviewers. A qualitative narrative synthesis was conducted using a thematic analysis approach. Setting Secondary or Tertiary Care centres that undertook management of Deep Neck Space Infections. Participants All adult patients with a deep neck space infection. Main outcome measures The role of imaging, radiologically guided aspiration and surgical drainage in DNSIs. Results 60 studies were reviewed. 31 studies reported on imaging modality, 51 studies reported treatment modality. Aside from a single RCT all other studies were observational (n=25) or case series (n=36). CT was used to diagnose DNSI in 78% of patients, Mean percentage of management with open surgical drainage was 81% and 29.4% for radiologically guided aspiration. Qualitative analysis identified 7 major themes were identified on DNSI. Conclusion There are limited methodologically rigorous studies investigating DNSIs. CT imaging was the most used imaging modality. Surgical drainage was commonest treatment choice. Areas of further research on epidemiology, reporting guidelines and management are required.

Objective To conduct a feasibility whole-genome sequencing (WGS) study in families to identify genetic variants relevant to unexplained pregnancy loss. Methods We conducted a pilot WGS study of four families with recurrent pregnancy loss, including parents, healthy live births, and losses, which included an embryonic loss (<10 weeks’ gestation), fetal deaths (10-20 weeks’ gestation) and stillbirths (≥ 20 weeks’ gestation). We used the Illumina platform for WGS and state-of-the-art protocols to identify single nucleotide variants (SNVs) following various modes of inheritance. Results We identified 87 SNVs involving 75 genes in embryonic loss (n=1), 370 SNVs involving 228 genes in fetal death (n=3), and 122 SNVs involving 122 genes in stillbirth (n=2). Of these, 22 de novo, 6 autosomal dominant and an X-linked recessive SNVs were pathogenic (probability of being loss-of-function intolerant >0.9), impacting known genes (e.g., DICER1, FBN2, FLT4, HERC1, and TAOK1) involved in embryonic/fetal development and congenital abnormalities. Further, we identified missense compound heterozygous SNVs impacting genes (e.g., VWA5B2) in two fetal death samples that were absent from live births and population controls, providing evidence for haplosufficient genes relevant to pregnancy loss. Conclusions In this pilot study, we provide evidence for de novo and inherited SNVs relevant to pregnancy loss. Our findings provide justification for conducting WGS using larger numbers of families and warrant validation by targeted sequencing to ascertain causal variants. Elucidating genes causing pregnancy loss may facilitate the development of risk stratification strategies and novel therapeutics.

Objective: To compare labour outcomes in a midwifery continuity of care (MCoC) model to standard midwifery care. Design: Matched cohort study. Setting: Public healthcare during pregnancy and childbirth, Stockholm, Sweden. Population: Women giving birth at Karolinska University Hospital site Huddinge in Stockholm between January 1st, 2019 to August 31st, 2021. Methods: Propensity score matching was applied to obtain a matched set from the standard care group for every woman in the MCoC model. Based on the matched cohort, we estimated risk ratios (RR) for binary outcomes with 95% confidence intervals (CI). Main Outcome Measures: Interventions during labor, mode of birth, and preterm birth (<37 gestational weeks). Results: Compared with standard care, women in the MCoC model were more likely to give birth spontaneously (RR 1.06 95% CI 1.02-1.10), and less likely to have an elective caesarean section on maternal request (RR 0.24 95% CI 0.11-0.51). The risk of preterm birth was reduced in the MCoC group (RR 0.51 95% CI 0.32-0.82). Conclusions: The MCoC model was associated with fewer medical interventions and improved maternal and neonatal outcomes.

BACKGROUND: Intraoperative MRI (iMRI) is a definitive technology in neurosurgery that has been used effectively to maximize outcomes for transsphenoidal resection of pituitary tumors. IMRI has been seen to provide optimal visualization of surrounding vital neurovascular structures and has helped surgeons achieve gross total resection. The use of iMRI in the community hospital setting has not been documented in the current literature as of yet. OBJECTIVE: This study aims to provide insight into the experiences of iMRI use in a community hospital setting and add to the growing literature of iMRi use for transsphenoidal resection of pituitary tumors. METHODS: A retrospective review of 56 patients who underwent iMRI guided transsphenoidal pituitary tumor resection at Northwestern Medicine Central Dupage Hospital (from November 2011 to April 2018) was performed. RESULTS: Gross total resection was found in 67% (n=37) of patients who underwent iMRI. 33% (n=19) did not achieve gross total resection of their pituitary mass. IMRi was used exactly one time during the case in 96% (n=54) of patients. IMRi was used more than once during the case in 4% (n=2) of patients. Post operative tumor residual was found in 32% (n=6) of patients who had available post-operative MRI studies (n=19). CONCLUSIONS: Our study shows that iMRI can be useful in a community hospital setting to achieve gross total resection during transsphenoidal pituitary tumor resection. It also demonstrates the ability and need to utilize iMRI only one time during a case which lends itself to operative efficiency.

To optimize the extraction process and activity detection of total flavonoids from Ficus Pumila. A Box–Behnken design of response surface methodology was employed to further optimize ultrasonic-assisted extraction (UAE) conditions for Ficus Pumila stems total flavonoids ( FPSTF). The results showed that optimized extraction conditions were ultrasonic power of 240 W, solvent concentration of 61%, ultrasonic time of 61 min and liquid-solid ratio of 25 mL/g. Under these conditions, the mean experimental value of extraction yield (1.07%) was achieved, which was about 2.14 times that of ethanol leaching extraction. As compared to FPSTF, FPSTF after purification ( FPSPTF) had higher purity of 11.09%, which was nearly 4.37 times higher than that of FPSTF (2.54%). As compared to FPSTF, FPSPTF had higher α-glucosidase and α-amylase inhibitory activities as well as DPPH· and ABTS·+ scavenging activities with an IC 50 value of 0.005, 0.008, 0.22 and 0.08 mg/mL, which was 6.00, 16.50, 1.68 and 2.50 times higher than that of FPSTF (0.030, 0.132, 0.37 and 0.20 mg/mL). FPSPTF from F. Pumila could be considered as multifunctional bioactive ingredients to be used in anti-hyperglycemic pharmaceutical formulation and antioxidant.

RP7214 is a potent and selective inhibitor of human mitochondrial enzyme dihydroorotate dehydrogenase (DHODH). This paper describes the results from a Phase 1 study that evaluated safety and pharmacokinetics of single and multiple ascending doses (SAD and MAD) and the food effect of RP7214 in healthy subjects. Target engagement of DHODH was also evaluated. A randomized, double-blind, placebo-controlled trial of single-dose (100, 200, and 400 mg QD) and multiple doses (200 and 400 mg BID for 7 days) followed by food effect at a single dose of 200 mg was conducted. A total of 18 healthy volunteers (HVs) (6 subjects in each of three cohorts) in the SAD part, 12 (6 subjects each in two cohorts) in the MAD part, and 12 in the food effect study were enrolled. RP7214 was well tolerated at all dose levels. None of the subjects reported any RP7214-related adverse events. RP7214 showed dose-proportional pharmacokinetics after single and multiple dosing. Steady-state concentrations were reached within about 3–6 days. The mean plasma half-life of RP724 at steady-state was approximately 13h. RP7214 showed accumulation on multiple dosing.. Food did not impact the absorption of RP7214. RP7214 showed dose-dependent inhibition of DHODH as measured by analyzing accumulating DHO levels, confirming target engagement. The rapid absorption and high systemic exposure of RP724 with a favorable safety profile shows the potential for the development of RP7214 in SARS-CoV-2 infection and acute myeloid leukemia. (NCT04680429). Keywords: RP7214, dihydroorotate dehydrogenase, SAD, MAD, HV

Background: The trustworthiness of randomised clinical trials (RCTs) is suffering a crisis of confidence. Objectives: We undertook an umbrella review of the research integrity literature concerning RCTs. Search strategy and selection criteria: Following prospective registration (https://osf.io/3ursn), two reviewers independently searched PubMed, Scopus, Cochrane Library and Google Scholar, without language or time restrictions until November 2021. We included systematic reviews covering any aspect of research integrity throughout the RCT lifecycle. Data collection and analysis: We assessed methodological quality using a modified AMSTAR-2 tool and collated the main findings. Main results: There were 55 relevant reviews summarising a total of 6001 studies (median per review 63; range 8-1106 studies). The overall quality of 53 (96.4%) reviews was critically low. Eight (14.6%) reviews focused on the general aspects of a RCT, 12 (21.8%) on the design and approval, 6 (10.9%) on the conduct and monitoring, 21 (38.2%) on the reporting of protocols and findings, one (1.8%) on post-publication concerns and 7 (12.7%) on future research and development. The integrity issues covered were varied, the most common being the importance of ethics (10/55, 18.2%) and transparency (10/55, 18.2%). Conclusions: Various research integrity issues covering RCT lifecycle, captured from mostly low-quality reviews, provided a broad overview emphasising the need for high level of ethical standards and professionalism. Many gaps in the RCT integrity landscape were also identified. There is a need to generate multistakeholder consensus to create specific RCT integrity standards.

In order to accurately predict creep deformation and damage evolution of nickel-based superalloy GH4169, a novel damage constitutive model, which can be called TTC CDM-based model, was proposed based on TTC relations and continuum damage mechanics (CDM). The stress and temperature dependence of constants were all determined in the novel model, which overcame the weakness of the traditional CDM-based model and made the model have the satisfactory abilities of interpolation and extrapolation. Microstructural study has revealed that the creep fracture mode gradually converts from intergranular brittle fracture to transgranular ductile fracture as the stress decreases. And the critical conditions were identified. It was determined that the novel model accurately predicted the minimum creep rate, rupture time, creep deformation and damage evolution process of GH4169. Furthermore, the nonlinear creep damage accumulation effect was also revealed by the novel model, i.e. the total creep life of GH4169 will be reduced if high stress or high temperature condition was applied first, which was consistent with previous experimental results of variable creep load.

Population genomic studies are increasing in the last decade, showing great potential to understand the evolutionary patterns in a great variety of organisms, mostly relying on RAD sequencing techniques to obtain reduced representations of the genomes. Among them, 2b-RAD can provide further secondary reduction to adjust study costs by using base-selective adaptors, although its impact on genotyping is unknown. Here we provide empirical comparisons on genotyping and genetic differentiation when using fully degenerate and base-selective adaptors and assess the impact of missing data. We built libraries with the two types of adaptors for the same individuals and generated independent and combined datasets with different missingness filters according to their presence (100%, 75% and 50%). Exploring locus-by-locus, we found 92% of identical genotypes between both libraries of the same individual when using loci present in 100% of the samples, which decreased to 35% when working with loci present in at least 50% of them. We show that missing data is a major source of individual genetic differentiation. The loci discordant by genotyping were in low frequency (7.67%) in all filtered files. Only 0.96% were directly attributable to base-selective adaptors, and 6.44% underestimated heterozygosity in NN libraries, of which ca. 70% had <10 reads per locus indicating that sufficient read depth should be ensured for a correct genotyping. Our work confirms that 2b-RAD libraries using base-selective adaptors are a robust tool to use in population genomics of species with large genome sizes.

Kikuchi disease is an uncommon, self-limited disease that mimics malignant lymphoma and tubercular lymphadenitis in presentation but with an excellent prognosis. We present a case of a 20-year-old Asian female with swelling at the angle of the mandible along with fever as a result of Kikuchi disease.

Schwannoma is a benign tumour originating from Schwann cells in the peripheral nerve sheath. Schwannoma can occur in the head and neck area but rarely occurs in nasal cavity and paranasal sinuses. No race or gender predilection. Often occurred at 6-78 years with highest incidence in 2nd and 4th decade

Sarcoptic mange, a disease caused by the burrowing mite Sarcoptes scabiei, is globally endemic and an emerging threat to wildlife. Although many studies have shown that wildlife diseases play key roles in biodiversity conservation, knowledge about sarcoptic mange is still insufficient. In this study, we aim to improve the understanding of the impacts of sarcoptic mange on wildlife populations, the mechanisms involved in its ecoepidemiology, and the associated risks to public and ecosystem health by investigating mass death events in gorals and serows in the Qinling Mountains. We conducted interviews with practitioners and local people in the central Qinling Mountains. From the same locations, we collected 24 cutaneous samples from various animals and surveillance data from infrared cameras. Pathological, parasitological and microbiological examinations of the samples were performed. Mite-induced cutaneous lesions, mites and eggs were observed in samples from dead gorals and one dead serow, but not in other species. Molecular analysis confirmed the mites to be S. scabiei that originated from rabbits. The data obtained from the interviews and infrared cameras indicated that the death of wildlife was related to sarcoptic mange infection and that there had been a decrease in the goral population since the outbreak of the disease. We confirmed that sarcoptic mange was the major cause of the mass death events and may have spread from the western to eastern Qinling Mountains. Based on our findings, we propose several protection strategies to help preserve biodiversity in the Qinling Mountains.

Background: Irinotecan and temozolmide achieve objective responses in patients with Ewing sarcoma which recurrences after initial therapy. Optional dose schedules have not been defined. Procedure: We reviewed published series of patients treated with irinotecan and temozolomide for Ewing sarcoma which recurred after initial therapy. We compared objective response rates for patients who received 5 day irinotecan treatment schedules to response rates for patients who achieved 10 day irinotecan treatment schedules. Results: Among 94 patients treated with a 10 day irinotecan schedule there were 48 objective responses (51%). Among 218 patients treated with a 5 day irinotecan schedule there were 65 responses (30%). Conclusion: When we use irinotecan to treat Ewing sarcoma we should administer 10 days of treatment.

As non-vascular plants, which lack lignin for protection, bryophytes support themselves in harsh environment by producing various chemicals. In response to cold stress, lipids play a crucial role in cell adaptation and energy storage. Specifically, bryophytes survive at low temperatures by producing very long-chain polyunsaturated fatty acids (vl-PUFAs). However, a systematic knowledge and comprehensive understanding of the cold acclimation of bryophytes is limited. To overcome this obstacle, we performed lipid profiling using ultra-high performance liquid chromatography-quadrupole time of flight mass spectrometry (UHPLC-QTOF-MS) of two moss species ( Bryum pseudotriquetrum and Physcomitrium patens) cultivated at standard condition compared to those cultivated at cold stressed condition. The potential biomarkers were identified by multivariate statistical analysis in each species. In B. pseudotriquetrum, we found that the phospholipids and glycolipids increased significantly under cold stress, while storage lipids decreased. The accumulation of the lipids with high unsaturation degrees (i.e. at least one fatty acyl chain contains more than two double bonds) mostly appear in phospholipids and glycolipids. However, this trend cannot be observed in P. patens. This suggests that different moss species may undergo a different lipid metabolic pathway of cold adaptation. Our findings present a deeper understanding of how mosses are adapted to cold temperature and provide a basis for future studies.

This study presents a system using an image processing technique that evaluates the pavement condition from an image. Pavement condition evaluation is an integral part of roads and highway maintenance works, which mostly depends on human inspection. Although recently some researches have been conducted on road condition detection with image processing, these researches used huge databases and deep CNNs that require expansive computer and longer training time, which limits the use of deep CNN in practical problems where huge database collection is not possible always. To solve this problem, in this study, transfer learning in deep CNN is applied and with only 195 images in each category, pre-trained VGG-16 and Inception-ResNet v2 models are used for pavement condition evaluation. VGG-16 achieved more than 90% prediction accuracy, while Inception-ResNet v2 achieved more than 85% prediction accuracy. Moreover, to validate the performance, both models have been tested with random images collected from Google. Evaluating pavement conditions this way would reduce the need for human inspection. Finally, the outcome of the study shows that the transfer learning approach could be useful in research areas, especially in civil engineering, where image data is insufficient.

Brassica crops include various edible vegetable and plant oil crops, and their production is limited by low temperature. The key regulators of low-temperature resistance in Brassica remain largely unexplored. To identify post-transcriptional regulators of plant response to low temperature, we performed small RNA profiling, and found that 16 known miRNAs responded to cold treatment in Brassica rapa. The cold response of seven of those miRNAs were further confirmed by qRT-PCR and/or northern blotting analyses. In parallel, a genome-wide association study of 220 accessions of Brassica napus identified four candidate MIRNA genes, all of which were cold-responsive, at the loci associated with low temperature resistance. Specifically, these large-scale data analyses revealed a link between miR1885 and the plant response to low temperature in both B. rapa and B. napus. Using 5′ rapid amplification of cDNA ends approach, we validated that miR1885 can cleave its putative target gene transcripts, Bn.TIR.A09 and Bn.TNL.A03, in B. napus. Furthermore, overexpression of miR1885 in B. napus decreased the mRNA abundance of Bn.TIR.A09 and Bn.TNL.A03 and resulted in increased sensitivity to low temperature. Knocking down of miR1885 in B. napus led to increased mRNA abundance of its targets and improved rapeseed tolerance to low temperature. Together, our results suggested that the loci of miR1885 and its targets could be potential candidates for the molecular breeding of low temperature-tolerant Brassica crops.