bluuebunny/crossref_metadata_2025 huggingface dataset:
The microbial communities (bacteria, algae, zooplankton, and fungi) improved biofloc technology including the nitrogen-related material cycle in Litopenaeus vannamei farms
Authors: Yun Hyun-Sik , Kim Dong-Hyun , Kim Jong-Guk , Kim Young-Saeng , Yoon Ho-Sung
Published: November 2022

Microbes are essential in biofloc technology for controlling nitrogen levels in water. The composition and function of microorganisms with biofloc systems were reported; however, data on microorganisms other than bacteria, such as algae (which are essential in the nitrogen cycle) and zooplankton (which are bacterial and algal predators), remain limited. The microbial communities (including bacteria, algae, zooplankton, and fungi) were investigated in shrimp farms using biofloc technology. Using Illumina MiSeq sequencing, the V4 region of 18S rRNA and the V3–V4 region of 16S rRNA were utilized for the analysis of the eukaryotic and prokaryotic microbial communities. As a result, it was found that the biofloc in the shrimp farm consisted of 48.73%–73.04% eukaryotic organisms and 26.96%–51.27% prokaryotic organisms. In these shrimp farms, prokaryotic microbial communities had higher specie richness and diversity than eukaryotic microbial communities. However, the eukaryotic microbial communities were more abundant than their prokaryotic counterparts, while algae and zooplankton dominated them. It was discovered that the structures of the microbial communities in the shrimp farms seemed to depend on the effects of predation by zooplankton and other related organisms. The results provided the nitrogen cycle in biofloc systems by the algal and bacterial groups in microbial communities.
Revising the stretch reflex threshold method to measure stretch hyperreflexia in cerebral palsy
Authors: Valadão Pedro , Bar-On Lynn , Cenni Francesco , Piitulainen Harri , Avela Janne , Finni Taija
Published: November 2022

Hyper-resistance is an increased resistance to passive muscle stretch, a common feature in neurological disorders. Stretch hyperreflexia, an exaggerated stretch reflex response, is the neural velocity-dependent component of hyper-resistance, and has been quantitatively measured using the stretch reflex threshold (i.e., joint angle at the stretch reflex electromyographic onset). In this study, we introduce a correction in how the stretch reflex threshold is calculated, by accounting for the stretch reflex latency (i.e., time between the stretch reflex onset at the muscle spindles and its appearance in the electromyographic signal). Furthermore, we evaluated how this correction affects the stretch reflex threshold in children and young adults with spastic cerebral palsy. A motor-driven ankle dynamometer induced passive ankle dorsiflexions at four incremental velocities in 13 children with cerebral palsy (mean age: 13.5 years, eight males). The stretch reflex threshold for soleus and medial gastrocnemius muscles was calculated as 1) the joint angle corresponding to the stretch reflex electromyographic onset (i.e., original method); and as 2) the joint angle corresponding to the electromyographic onset minus the individual Hoffmann-reflex latency (i.e., latency corrected method). The group linear regression slopes between stretch velocity and stretch reflex threshold differed in both muscles between methods (p < 0.05). While the original stretch reflex threshold was velocity dependent in both muscles (p < 0.05), the latency correction rendered it velocity independent. Thus, the effects of latency correction on the stretch reflex threshold are substantial, especially at higher stretch velocities, and should be considered in future studies.
Introducing uncertainties in composite indicators. The case of the Impact Chain risk assessment framework
Authors: Melo-Aguilar Camilo , Agulles Miguel , Jordà Gabriel
Published: November 2022

The use of composite indices is widespread in many fields of knowledge but a common problem associated to those type of indices is how to introduce uncertain knowledge on them. One example would be the Impact Chain framework for risk assessment. This methodology has proven to be a robust and effective approach to set up the conceptual framework associated to a given risk allowing to naturally consider the different components that shape that risk. However, the operationalization of the impact chain may not be straightforward, in particular due to the inherent uncertainties associated to the selected indicators and the assigned weights. In this paper, we propose to use a probabilistic framework that would allow to consider uncertain knowledge in the composite indicator computation. Moreover, in the framework of the UNCHAIN project, a web-based tool has been developed to ease the task of implementing that methodology. This web-based application is designed as a multidimensional tool to consider uncertainties in any type of composite indicator, thus, its scope goes beyond the Impact Chain and risk analysis framework. For illustrative purposes, the tool has been applied to a case study on the risk of loss tourist attractiveness due to heat stress conditions on the Balearic island, Spain. This case study is used to show how uncertainties in different components of the impact chain can affect the robustness of the final risk assessment. Also, the tool provides an estimate of the sensitivity of the final risk to each component, which can be used to guide risk mitigation strategies. Finally, a proposal for the validation of the risk assessment is presented.
Identifying hypertensive disorders of pregnancy, a comparison of two epidemiologic definitions
Authors: Cheetham T. Craig , Shortreed Susan M. , Avalos Lyndsay A. , Reynolds Kristi , Holt Victoria L. , Easterling Thomas R. , Portugal Cecilia , Zhou Hui , Neugebauer Romain S. , Bider Zoe , Idu Abisola , Dublin Sascha
Published: November 2022

Introduction

Studies of hypertension in pregnancy that use electronic health care data generally identify hypertension using hospital diagnosis codes alone. We sought to compare results from this approach to an approach that included diagnosis codes, antihypertensive medications and blood pressure (BP) values.

Materials and methods

We conducted a retrospective cohort study of 1,45,739 pregnancies from 2009 to 2014 within an integrated healthcare system. Hypertensive pregnancies were identified using the “BP-Inclusive Definition” if at least one of three criteria were met: (1) two elevated outpatient BPs, (2) antihypertensive medication fill plus an outpatient hypertension diagnosis, or (3) hospital discharge diagnosis for preeclampsia or eclampsia. The “Traditional Definition” considered only delivery hospitalization discharge diagnoses. Outcome event analyses compared rates of preterm delivery and small for gestational age (SGA) between the two definitions.

Results

The BP-Inclusive Definition identified 14,225 (9.8%) hypertensive pregnancies while the Traditional Definition identified 13,637 (9.4%); 10,809 women met both definitions. Preterm delivery occurred in 20.9% of BP-Inclusive Definition pregnancies, 21.8% of Traditional Definition pregnancies and 6.6% of non-hypertensive pregnancies; for SGA the numbers were 15.6, 16.3, and 8.6%, respectively (p < 0.001 for all events compared to non-hypertensive pregnancies). Analyses in women meeting only one hypertension definition (21–24% of positive cases) found much lower rates of both preterm delivery and SGA.

Conclusion

Prevalence of hypertension in pregnancy was similar between the two study definitions. However, a substantial number of women met only one of the study definitions. Women who met only one of the hypertension definitions had much lower rates of adverse neonatal events than women meeting both definitions.
Sex-specific differences in atherosclerosis, thrombospondin-1, and smooth muscle cell differentiation in metabolic syndrome versus non-metabolic syndrome mice
Authors: Gupta Shreya , Khanal Saugat , Bhavnani Neha , Mathias Amy , Lallo Jason , Kiriakou Ariana , Ferrell Jessica , Raman Priya
Published: November 2022

Introduction

Metabolic syndrome (MetS) amplifies the risks of atherosclerosis. Despite well-known sexual dimorphism in atherosclerosis, underlying mechanisms are poorly understood. Our previous findings highlight a proatherogenic protein, thrombospondin-1 (TSP-1), in hyperglycemia- or hyperleptinemia (mimicking obesity)-induced atherosclerosis. However, the role of TSP-1 in the development of atherosclerosis prompted by co-existing hyperglycemia and obesity, characteristic of MetS, is unknown. The goal of this study was to examine sex-specific differences in lesion progression in a model of combined MetS and atherosclerosis (KKAyApoE) and interrogate how these differences relate to TSP-1 expression.

Methods

Male and female KKAy+/−ApoE–/– (with ectopic agouti gene expression) and age-matched non-agouti KKAy–/–ApoE–/– littermates were placed on a standard laboratory diet from 4 to 24 weeks age followed by blood and tissue harvests for biochemical, molecular, and aortic root morphometric studies.

Results

Metabolic profiling confirmed MetS phenotype of KKAy+/−ApoE–/–; however, only male genotypes were glucose intolerant with elevated VLDL-cholesterol and VLDL-triglyceride levels. Aortic root morphometry demonstrated profound lipid-filled lesions, increased plaque area, and augmented inflammatory and SMC abundance in MetS vs non-MetS males. This increase in lesion burden was accompanied with elevated TSP-1 and attenuated LMOD-1 (SM contractile marker) and SRF (transcriptional activator of SM differentiation) expression in male MetS aortic vessels. In contrast, while lipid burden, plaque area, and TSP-1 expression increased in MetS and non-MetS female mice, there was no significant difference between these genotypes. Increased collagen content was noted in MetS and non-MetS genotypes, specific to female mice. Measurement of plasma testosterone revealed a link between the atherogenic phenotype and abnormally high or low testosterone levels. To interrogate whether TSP-1 plays a direct role in SMC de-differentiation in MetS, we generated KKAy+/− mice with and without global TSP-1 deletion. Immunoblotting showed increased SM contractile markers in male KKAy+/−TSP-1–/– aortic vessels vs male KKAy+/−TSP-1+/ +. In contrast, TSP-1 deletion had no effect on SM contractile marker expression in female genotypes.

Conclusion

Together, the current study implicates a role of plasma testosterone in sex-specific differences in atherosclerosis and TSP-1 expression in MetS vs non-MetS mice. Our data suggest a sex-dependent differential role of TSP-1 on SMC de-differentiation in MetS. Collectively, these findings underscore a fundamental link between TSP-1 and VSMC phenotypic transformation in MetS.
Gender discrepancies in predictors for newly onset cardiovascular events and metabolic syndrome in elderly patients from rural China
Authors: Yu Shasha , Guo Xiaofan , Li GuangXiao , Yang Hongmei , Zheng Liqiang , Sun Yingxian
Published: November 2022

Objective

The study aimed to estimate the possible predictors of cardiovascular events (CVEs) in elderly patients with metabolic syndrome (MetS) from rural China. Moreover, we also attempted to find the potential risk factors for newly diagnosed MetS.

Methods

The Northeast China Rural Cardiovascular Health Study (NCRCHS) is a community-based prospective cohort study carried out in rural areas of northeast China. Approximately 1,059 elderly patients with MetS but no cardiovascular diseases and 1,565 elderly patients without MetS at baseline were enrolled in this study. They underwent a physical examination, completed a questionnaire in 2012–2013, and were followed up during 2015–2017. Cox proportional hazard analysis was conducted to assess the possible predictors of newly developed CVEs, and multivariate analysis was used to estimate the risk factors of newly diagnosed MetS.

Results

The common predictors of newly developed CVEs in both men and women were family history of stroke (HR [hazard ratios] female: 1.696; HR male: 2.504) and soybean consumption (HR female: 0.253; HR male: 0.130). Moreover, minority race (HR: 0.109), systolic blood pressure (SBP) (HR: 1.021), current drinking habits (HR: 2.551), family history of hypertension (HR: 2.297), LDL-C (HR: 1.669), 5,000–20,000 CNY/year annual income (HR: 0.290), and strenuous physical activity (HR: 0.397) were predictors of CVEs only in male elderly patients. For newly diagnosed MetS, body mass index (OR female: 1.212; OR male: 1.207) and fasting blood glucose (OR female: 1.305; OR male: 1.217) were common risk factors in both genders, whereas age (OR:0.958) was a protective factor in men and > 9-h/day sleep duration (OR:0.212) was a protective factor in women. In addition, SBP (OR:1.014) ≥4 times/day, bean consumption (OR:1.955), and uric acid (OR:1.005) increased the risk of MetS in men but not in women.

Conclusion

Our study identified many effective predictors of CVEs in rural elderly patients with MetS and confirmed the presence of a gender-based discrepancy. Moreover, we also identified additional risk factors, along with the traditional ones, for newly diagnosed MetS in rural elderly patients.
Response of a large deep-seated gravitational slope deformation to meteorological, seismic, and deglaciation drivers as measured by InSAR
Authors: Rabus Bernhard , Engelbrecht Jeanine , Clague John J. , Donati Davide , Stead Doug , Francioni Mirko
Published: November 2022

We analyze the sensitivity of a large (area extent ∼3 km2), deep-seated gravitational slope deformation (Fels slide, Alaska Range) to three specific drivers: (i) liquid surface water input from ERA-5 reanalysis snow melt and rainfall; (ii) locally projected seismic activity of Alaskan earthquakes; and (iii) lowering of Fels Glacier at the slide toe estimated from topographic data. A surface displacement map-series is derived from 1991 to 2016 spaceborne multi-sensor InSAR data (ERS, RADARSAT-1/2, ALOS, TerraSAR-X) using adaptive demodulation to unwrap interferograms of variable spatial resolution and quality. On this series we use independent component analysis (ICA) to uncover five displacement patterns that map to independently moving domains of the slide and then correlate the corresponding temporal pattern intensities with the suspected drivers. We find significant sub-annual correlation between displacement pattern intensities and seasonal water input variations. The correlation can be optimized, for each ICA pattern, by choosing appropriate values of temporal smoothing and lag to create depth-propagated versions of the water input driver. Lag time results ranging from one to 3 weeks relate to shallower and deeper propagations of water input, driving the different deformation patterns. For two of the deformation patterns, seasonal sensitivity to water input was strongly amplified by the 2002 Mw7.9 Denali earthquake. Sensitivity of these patterns remained high for 4 years until abruptly dropping to below pre-earthquake values, which suggests a highly non-linear modulation by the seismic driver. Other deformation patterns show a steady intensity increase that appears linked to the deglaciation driver. Despite these observations, the inter-annual variations in ICA pattern intensities show no clear predictability by individual drivers or driver combinations. This suggests that the mechanical and hydraulic evolution of the slide, especially after damaging events such as earthquakes or heavy rainfall, is a crucial factor not adequately modeled in our approach. Despite this limitation, our analysis provides the first direct evidence that the Fels slide comprises several independently moving domains that respond differently to the suspected drivers as is suggestive of a complex slope deformation.
Earth system science applications of next-generation SEM-EDS automated mineral mapping
Authors: Han Shujun , Lӧhr Stefan C. , Abbott April N. , Baldermann Andre , Farkaš Juraj , McMahon William , Milliken Kitty L. , Rafiei Mehrnoush , Wheeler Cassandra , Owen Michael
Published: November 2022

Sedimentary rocks contain a unique record of the evolution of the Earth system. Deciphering this record requires a robust understanding of the identity, origin, composition, and post-depositional history of individual constituents. Petrographic analysis informed by Scanning Electron Microscope - Energy Dispersive Spectroscopy (SEM-EDS) mineral mapping can reveal the mineral identity, morphology and petrological context of each imaged grain, making it a valuable tool in the Earth Scientist’s analytical arsenal. Recent technological developments, including quantitative deconvolution of mixed-phase spectra (producing “mixels”), now allow rapid quantitative SEM-EDS-based analysis of a broad range of sedimentary rocks, including the previously troublesome fine-grained lithologies that comprise most of the sedimentary record. Here, we test the reliability and preferred mineral mapping work flow of a modern Field-Emission scanning electron microscope equipped with the Thermofisher Scientific Maps Mineralogy mineral mapping system, focusing on mud/siltstones and calcareous shales. We demonstrate that SEM-EDS mineral mapping that implements 1) a strict error minimization spectral matching approach and 2) spectral deconvolution to produce ‘mixels’ for mixed-phase X-ray volumes can robustly identify individual grains and produce quantitative mineralogical data sets comparable to conventional X-ray diffraction (XRD) analysis (R2 > 0.95). The correlation between SEM-EDS and XRD-derived mineralogy is influenced by mineral abundance, processing modes and mapped area characteristics. Minerals with higher abundance (>10 wt%) show better correlation, likely the result of increased uncertainty for XRD quantification of low-abundance phases. Automated spectral deconvolution to produce ‘mixels’ greatly reduces the proportion of unclassified pixels, especially in the fine-grained fraction, ultimately improving mineral identification and quantification. Mapping of larger areas benefits bulk mineralogy analysis, while customized area size and shape allows high-resolution in situ mineralogical analysis. Finally, we review SEM-EDS-based mineral mapping applications in the Earth Sciences, via case studies illustrating 1) approaches for the quantitative differentiation of various mineral components including detrital (allogenic), syndepositional (authigenic) and burial diagenetic phases, 2) the origin and significance of lamination, 3) the effectiveness and appropriateness of sequential leaching in geochemical studies, and 4) the utility of mineral maps to identify target grains within specific petrological contexts for in situ geochemical or geochronological analysis.
Urban spatial structure and environmental efficiency: Empirical analysis from prefecture-level cities in China
Authors: Ye Jing , Wei Feng , Liu Xihe , Li Jinkai
Published: November 2022

China’s environmental problems are emerging with the continuous development of the economy and urbanization. The study of the impact of urban spatial structure on environmental efficiency has important significance concerning exploring ways to reduce the environmental cost of economic activity. Based on the fusion-corrected DMSP-OLS and NPP-VIIRS nighttime light data, this paper constructs spatial structure indicators of 276 prefecture-level cities and then empirically tests the impact of urban spatial structure on environmental efficiency using a fixed-effects model. The results show that: 1) The monocentric spatial structure has higher environmental efficiency than the polycentric spatial structure. 2) The mechanism analysis shows that the monocentric spatial structure could improve environmental efficiency through learning, sharing, and matching. 3) Population size and density have a robust moderating effect that when the resident population size of a city is more than 5 million or the population density is beyond 280 persons/km2, the monocentric spatial structure has a negative impact on environmental efficiency. In contrast, the polycentric spatial structure is more effective. 4) The point-based household registration policy adopted by the government to control population size has no significant impact on environmental efficiency, while the environmental information disclosure policy can effectively play a role. Our findings provide a basis for the Chinese government to formulate urban planning and environmental protection policies and offer the experience to other developing countries.
Case report: A novel heterozygous synonymous variant in deep exon region of NIPBL gene generating a non-canonical splice donor in a patient with cornelia de lange syndrome
Authors: Shi Meizhen , Liang Yuying , Xie Bobo , Wei Xianda , Zheng Haiyang , Gui Chunrong , Huang Rong , Fan Xin , Li Chuan , Wei Xiaojiao , Ma Yunting , Chen Shaoke , Chen Yujun , Gui Baoheng
Published: November 2022

Cornelia de Lange syndrome (CdLS) is an autosomal dominant or X-linked genetic disease with significant genetic heterogeneity. Variants of the NIPBL gene are responsible for CdLS in 60% of patients. Herein, we report the case of a patient with CdLS showing distinctive facial features, microcephaly, developmental delay, and growth retardation. Whole exome sequencing was performed for the patient, and a novel de novo heterozygous synonymous variant was identified in the deep region of exon 40 in the NIPBL gene (NM_133433.4: c. 6819G > T, p. Gly2273 = ). The clinical significance of the variant was uncertain according to the ACMG/AMP guidelines; however, based on in silico analysis, it was predicted to alter mRNA splicing. To validate the prediction, a reverse transcriptase-polymerase chain reaction was conducted. The variant activated a cryptic splice donor, generating a short transcript of NIPBL. A loss of 137 bp at the 3′ end of NIPBL exon 40 was detected, which potentially altered the open reading frame by inserting multiple premature termination codons. Quantitative real-time PCR analysis showed that the ratio of the transcription level of the full-length transcript to that of the altered short transcript in the patient was 5:1, instead of 1:1. These findings may explain the relatively mild phenotype of the patient, regardless of the loss of function of the truncated protein due to a frameshift in the mRNA. To the best of our knowledge, this study is the first to report a synonymous variant in the deep exon regions of the NIPBL gene responsible for CdLS. The identified variant expands the mutational spectrum of the NIPBL gene. Furthermore, synonymous variations may be pathogenic, which should not be ignored in the clinical and genetic diagnosis of the disease.
Controversies and expectations for the prevention of GVHD: A biological and clinical perspective
Authors: Watkins Benjamin , Williams Kirsten M.
Published: November 2022

Severe acute and chronic graft versus host disease (GVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation. Historically, cord blood and matched sibling transplantation has been associated with the lowest rates of GVHD. Newer methods have modified the lymphocyte components to minimize alloimmunity, including: anti-thymocyte globulin, post-transplant cyclophosphamide, alpha/beta T cell depletion, and abatacept. These agents have shown promise in reducing severe GVHD, however, can be associated with increased risks of relapse, graft failure, infections, and delayed immune reconstitution. Nonetheless, these GVHD prophylaxis strategies have permitted expansion of donor sources, especially critical for those of non-Caucasian decent who previously lacked transplant options. This review will focus on the biologic mechanisms driving GVHD, the method by which each agent impacts these activated pathways, and the clinical consequences of these modern prophylaxis approaches. In addition, emerging novel targeted strategies will be described. These GVHD prophylaxis approaches have revolutionized our ability to increase access to transplant and have provided important insights into the biology of GVHD and immune reconstitution.
Case report: A successful second autologous hematopoietic stem cell transplantation in refractory systemic sclerosis, with positive effect on skin involvement, pulmonary function and microcirculation
Authors: Haverkort D.A. , Kersten B.E. , van Rhenen A. , van der Velden W.J.F.M. , Vonk M.C.
Published: November 2022

Background

Systemic sclerosis (SSc) is a complex autoimmune disease characterized by inflammation, vasculopathy and fibrosis of the skin and internal organs. Treatment with autologous hematopoietic cell transplantation (HCT) for progressive SSc has improved overall and event-free survival rates significantly, but unfortunately disease progression after HCT is seen in a subset of patients. Data on the efficacy and safety of second HCT is scarce.

Case

We present a patient with diffuse cutaneous SSc and associated interstitial lung disease (ILD) who successfully underwent a second HCT for progressive disease five years after a first HCT. We describe changes in skin involvement and pulmonary involvement as well as the changes observed in sequential nailfold microcapillaroscopy (NCM), performed from first presentation up to this moment.

Conclusion

This case adds to the current limited literature on efficacy and safety of a second HCT in SSc refractory cases. Furthermore it outlines the potential of HCT on amelioration of microvasculopathy in SSc.
Nasal administration of anti-CD3 monoclonal antibody modulates effector CD8+ T cell function and induces a regulatory response in T cells in human subjects
Authors: Chitnis Tanuja , Kaskow Belinda J. , Case Junning , Hanus Katherine , Li Zhenhua , Varghese Johnna F. , Healy Brian C. , Gauthier Christian , Saraceno Taylor J. , Saxena Shrishti , Lokhande Hrishikesh , Moreira Thais G. , Zurawski Jonathan , Roditi Rachel E. , Bergmark Regan W. , Giovannoni Federico , Torti Maria F. , Li Zhaorong , Quintana Francisco , Clementi William A. , Shailubhai Kunwar , Weiner Howard L. , Baecher-Allan Clare M.
Published: November 2022

Background

Parenteral anti-CD3 Mab (OKT3) has been used to treat transplant rejection and parental administration of a humanized anti-CD3 Mab (Teplizumab) showed positive effects in diabetes. Nasal administration of anti-CD3 Mab has not been carried out in humans. Nasal anti-CD3 Mab suppresses autoimmune diseases and central nervous system (CNS) inflammation in animal models. We investigated the safety and immune effects of a fully humanized, previously uncharacterized nasal anti-CD3 Mab (Foralumab) in humans and its in vitro stimulatory properties.

Methods

In vitro, Foralumab were compared to UCHT1 anti-human CD3 mAb. For human administration, 27 healthy volunteers (9 per group) received nasal Foralumab or placebo at a dose of 10ug, 50ug, or 250ug daily for 5 days. Safety was assessed and immune parameters measured on day 1 (pre-treatment), 7, 14, and 30 by FACS and by scRNAseq.

Results

In vitro, Foralumab preferentially induced CD8+ T cell stimulation, reduced CD4+ T cell proliferation and lowered expression of IFNg, IL-17 and TNFa. Foralumab induced LAP, TIGIT, and KLRG1 immune checkpoint molecules on CD8+ and CD4+ T cells in a mechanism independent of CD8 T cells. In vivo, nasal Foralumab did not modulate CD3 from the T cell surface at any dose. Immune effects were primarily observed at the 50ug dose and consisted of reduction of CD8+ effector memory cells, an increase in naive CD8+ and CD4+ T cells, and reduced CD8+ T cell granzyme B and perforin expression. Differentially expressed genes observed by scRNAseq in CD8+ and CD4+ populations promoted survival and were anti-inflammatory. In the CD8+ TEMRA population there was induction of TIGIT, TGFB1 and KIR3DL2, indicative of a regulatory phenotype. In the memory CD4+ population, there was induction of CTLA4, KLRG1, and TGFB whereas there was an induction of TGF-B1 in naïve CD4+ T cells. In monocytes, there was induction of genes (HLA-DP, HLA-DQ) that promote a less inflammatory immune response. No side effects were observed, and no subjects developed human anti-mouse antibodies.

Conclusion

These findings demonstrate that nasal Foralumab is safe and immunologically active in humans and presents a new avenue for the treatment of autoimmune and CNS diseases.
High-precision DOA estimation for underwater acoustic signals based on sparsity adaptation
Authors: Jiao Lulu , Yang Xinghai , Quan Tianqi , Wang Jingjing
Published: November 2022

The direction of arrival (DOA) estimation technique is to obtain the direction information of the source when it reaches the array by processing and analyzing the received signal. In recent years, the DOA estimation of an array signal has been a research hotspot. For application scenarios with a small number of snapshots and a low signal-to-noise ratio, the compressive sensing theory has been commonly used to estimate the DOA of an array signal to achieve better estimation performance. However, the DOA estimation methods based on compressive sensing theory require information on source sparsity. Moreover, the influence of a complex underwater acoustic environment limits the accuracy of estimation algorithms. To address this limitation, this study proposes a high-precision DOA estimation model for underwater acoustic signals based on sparsity adaptation. The proposed model includes mainly two parts. In the first part, a source sparsity adaptive model based on a causal convolutional neural network is proposed. The model is used to address the constraint that the source sparsity should be known a priori when compressed sensing is used for DOA estimation. In the second part, a differential combination matching pursuit (DCMP) algorithm is adopted. First, a differentiated path filtering strategy is employed to reduce algorithm complexity and avoid the problem of invalid filtering. In addition, the combined optimization strategy is used to improve the prediction accuracy of the algorithm, providing an efficient error correction idea for the compressed sensing application to DOA estimation. The results of simulations conducted under seven different signal-to-noise ratios and using three different array types show that the proposed source sparsity adaptive model can reach an average prediction accuracy of 89.6%. In addition, compared with the other reconstruction algorithm accuracy, on the basis of ensuring low time complexity, the proposed DCMP algorithm can achieve an accuracy improvement of 9.99%–19.94% under seven different signal-to-noise ratio values. Moreover, the mean absolute error of the proposed DCMP algorithm is lower by approximately 0.05°–14° than those of the OMP and MMP algorithms.
When and how should we use imaging in individuals at risk of rheumatoid arthritis?
Authors: Harnden Kate , Di Matteo Andrea , Mankia Kulveer
Published: November 2022

In recent years rheumatologists have begun to shift focus from early rheumatoid arthritis (RA) to studying individuals at risk of developing the disease. It is now possible to use blood, clinical and imaging biomarkers to identify those at risk of progression before the onset of clinical synovitis. The use of imaging, in particular ultrasound (US) and magnetic resonance imaging (MRI), has become much more widespread in individuals at-risk of RA. Numerous studies have demonstrated that imaging can help us understand RA pathogenesis as well as identifying individuals at high risk of progression. In addition, imaging techniques are becoming more sophisticated with newer imaging modalities such as high-resolution peripheral quantitative computed tomography (HR-pQRCT), nuclear imaging and whole body-MRI (WB-MRI) starting to emerge. Imaging studies in at risk individuals are heterogeneous in nature due to the different at-risk populations, imaging modalities and protocols used. This review will explore the available imaging modalities and the rationale for their use in the main populations at risk of RA.
A novel murine model of autoimmune dysautonomia by α3 nicotinic acetylcholine receptor immunization
Authors: Yamakawa Makoto , Nakane Shunya , Ihara Eikichi , Tawara Nozomu , Ikeda Hiroko , Igarashi Yoko , Komohara Yoshihiro , Takamatsu Koutaro , Ikeda Tokunori , Tomita Yusuke , Murai Shoichi , Ando Yukio , Mukaino Akihiro , Ogawa Yoshihiro , Ueda Mitsuharu
Published: November 2022

We aimed to establish a novel murine model of autoimmune autonomic ganglionopathy (AAG), which represents autoimmune dysautonomia, associated with MHC class II to understand its pathomechanism and the pathogenicity of nicotinic acetylcholine receptor (nAChR) antibodies. The amino acid sequence of the mouse nAChRα3 protein was analyzed using an epitope prediction tool to predict the possible MHC class II binding mouse nAChRα3 peptides. We focused on two nAChRα3 peptides in the extracellular region, and experimental AAG (EAAG) was induced by immunization of C57BL/6 mice with these two different peptides. EAAG mice were examined both physiologically and histologically. Mice with EAAG generated nAChRα3 antibodies and exhibited autonomic dysfunction, including reduced heart rate, excessive fluctuations in systolic blood pressure, and intestinal transit slowing. Additionally, we observed skin lesions, such as alopecia and skin ulcers, in immunized mice. Neuronal cell density in the sympathetic cervical ganglia in immunized mice was significantly lower than that in control mice at the light microscopic level. We interpreted that active immunization of mice with nAChRα3 peptides causes autonomic dysfunction similar to human AAG induced by an antibody-mediated mechanism. We suggested a mechanism by which different HLA class II molecules might preferentially affect the nAChR-specific immune response, thus controlling diversification of the autoantibody response. Our novel murine model mimics AAG in humans and provides a useful tool to investigate its pathomechanism.
Dual attentive fusion for EEG-based brain-computer interfaces
Authors: Du Yuanhua , Huang Jian , Huang Xiuyu , Shi Kaibo , Zhou Nan
Published: November 2022

The classification based on Electroencephalogram (EEG) is a challenging task in the brain-computer interface (BCI) field due to data with a low signal-to-noise ratio. Most current deep learning based studies in this challenge focus on designing a desired convolutional neural network (CNN) to learn and classify the raw EEG signals. However, only CNN itself may not capture the highly discriminative patterns of EEG due to a lack of exploration of attentive spatial and temporal dynamics. To improve information utilization, this study proposes a Dual Attentive Fusion Model (DAFM) for the EEG-based BCI. DAFM is employed to capture the spatial and temporal information by modeling the interdependencies between the features from the EEG signals. To our best knowledge, our method is the first to fuse spatial and temporal dimensions in an interactive attention module. This module improves the expression ability of the extracted features. Extensive experiments implemented on four publicly available datasets demonstrate that our method outperforms state-of-the-art methods. Meanwhile, this work also indicates the effectiveness of Dual Attentive Fusion Module.
The 2022 ENCR Recommendations on recording and reporting of urothelial tumours of the urinary tract
Authors: Galceran Jaume , Parada David , Eden Michael , Tumino Rosario , Warren Anne Yvonne , Martos Carmen , Neamtiu Luciana , Visser Otto , Daubisse-Marliac Laetitia
Published: November 2022

An updated European Network of Cancer registries (ENCR) Recommendations on Recording and Reporting of Urothelial Tumours of the Urinary Tract had been published in 2022. After the publication by the ENCR of the “Recommendations for coding bladder cancers” in 1995, knowledge about the biology and pathology of urinary tract tumors and their classification has varied and increased substantially. On the other hand, several studies have shown that cancer registries use different definitions, criteria for inclusion and coding of urothelial tumors. This great variability among registries affects not only the criteria for recording (registration, coding and classification) but also the criteria of reporting (counting in the statistics of incidence and survival) urinary tract tumors. This causes difficulties in the data comparability from different registries. Recording and reporting of urothelial tumors requires the application of standard criteria that must take into account the combination of the multiple aspects as the primary topography, the histological type, the grade, the extent of invasion, the multi-centricity, the progressions and the time interval between tumors. This led to the creation of a Working Group of the ENCR that developed these recommendations on the recording and reporting of urothelial tumors of the urinary tract. This article reports these recommendations and the rationale for each.
Case report: High-grade endometrial stromal sarcoma with adrenal glands metastases: An unreported site of metastasis
Authors: Zhang Tao , Feng Run-lin , Yin Si-fan , Feng Wen-bo , Yin Zhi-yuan , Wang Hao , Ke Chang-Xing
Published: November 2022

Background

Endometrial stromal sarcoma is a relatively rare malignant tumor that derives from the malignant transformation of primitive uterine mesenchymal cells. It can lead to distant metastases. High-grade endometrial stromal sarcoma is extremely rare. The adrenal glands are an unreported site of metastasis.

Case summary

A 71-year-old woman with a diagnosis of endometrial stromal sarcoma 30 months ago. After receiving treatment with radiotherapy and chemotherapy, the patient was kept asymptomatic during the follow-up until 2 years later, when she complained of dyspnea. Pulmonary and right adrenal gland metastases were detected by 18F-FDG PET/CT. The right upper lobe mass was diagnosed as a high-grade endometrial stromal sarcoma metastasis after postoperative pathology. Due to the patient’s high risk of surgery, as she had many underlying diseases, we performed adequate preoperative preparation. The physical examination revealed that a hard mass was palpable in the right renal area. The right adrenal mass was resected in our hospital. Immunohistochemistry showed ER (-), PR (-), CD10 (+), P16 (+), Ki-67 (50%). The final diagnosis on pathological examination was a high-grade ESS metastatic to the right adrenal gland. The patient continued treatment in other hospitals after surgical resection. After four months of postoperative follow-up, metastasis was detected again during a PET/CT examination at an outside hospital.

Conclusion

Endometrial stromal sarcoma is rare, and the adrenal glands are an unreported site of metastasis. It has no specific clinical symptoms and mainly found for other reasons. The diagnosis still depends on pathology and immunohistochemistry. If there is no relevant past history, it is difficult to exclude a primary adrenal tumor.
Development and validation of a radiomic nomogram based on pretherapy dual-energy CT for distinguishing adenocarcinoma from squamous cell carcinoma of the lung
Authors: Chen Zhiyong , Yi Li , Peng Zhiwei , Zhou Jianzhong , Zhang Zhaotao , Tao Yahong , Lin Ze , He Anjing , Jin Mengni , Zuo Minjing
Published: November 2022

Objective

Based on pretherapy dual-energy computed tomography (DECT) images, we developed and validated a nomogram combined with clinical parameters and radiomic features to predict the pathologic subtypes of non-small cell lung cancer (NSCLC) — adenocarcinoma (ADC) and squamous cell carcinoma (SCC).

Methods

A total of 129 pathologically confirmed NSCLC patients treated at the Second Affiliated Hospital of Nanchang University from October 2017 to October 2021 were retrospectively analyzed. Patients were randomly divided in a ratio of 7:3 (n=90) into training and validation cohorts (n=39). Patients’ pretherapy clinical parameters were recorded. Radiomics features of the primary lesion were extracted from two sets of monoenergetic images (40 keV and 100 keV) in arterial phases (AP) and venous phases (VP). Features were selected successively through the intra-class correlation coefficient (ICC) and the least absolute shrinkage and selection operator (LASSO). Multivariate logistic regression analysis was then performed to establish predictive models. The prediction performance between models was evaluated and compared using the receiver operating characteristic (ROC) curve, DeLong test, and Akaike information criterion (AIC). A nomogram was developed based on the model with the best predictive performance to evaluate its calibration and clinical utility.

Results

A total of 87 ADC and 42 SCC patients were enrolled in this study. Among the five constructed models, the integrative model (AUC: Model 4 = 0.92, Model 5 = 0.93) combining clinical parameters and radiomic features had a higher AUC than the individual clinical models or radiomic models (AUC: Model 1 = 0.84, Model 2 = 0.79, Model 3 = 0.84). The combined clinical-venous phase radiomics model had the best predictive performance, goodness of fit, and parsimony; the area under the ROC curve (AUC) of the training and validation cohorts was 0.93 and 0.90, respectively, and the AIC value was 60.16. Then, this model was visualized as a nomogram. The calibration curves demonstrated it’s good calibration, and decision curve analysis (DCA) proved its clinical utility.

Conclusion

The combined clinical-radiomics model based on pretherapy DECT showed good performance in distinguishing ADC and SCC of the lung. The nomogram constructed based on the best-performing combined clinical-venous phase radiomics model provides a relatively accurate, convenient and noninvasive method for predicting the pathological subtypes of ADC and SCC in NSCLC.
Better vertebrae remodeling in pediatric spinal eosinophilic granuloma patients treated with kyphoplasty and short-term posterior instrumentation: A minimal two-year follow-up with historical controls
Authors: Zheng Yiming , Zhang Zhiqiang , Wang Dahui
Published: November 2022

Objective

To assess the validity and safety of kyphoplasty combined with short-term posterior instrumentation to treat children with vertebrae plana due to eosinophilic granuloma (EG).

Patients and Methods

Clinical data of EG patients, who received kyphoplasty and short-term instrumentation from March 2019 to March 2020, were retrospectively reviewed. The recovery of diseased vertebrae was assessed and compared with historical case data.

Results

Nine patients with EG had received kyphoplasty and short-term posterior instrumentation. The mean age at initial treatment was 66.7 months old (range, 28–132 months). The average number of follow-up months was 26.7. (range, 24–30 months).Four and 5 cases presented with thoracic and lumbar vertebral destruction, respectively. Under Garg's classification, 7 and 2 cases were classified as Grade IIA and IIB, respectively. The average diseased vertebral heights at 1-year and 2-year after surgery were significantly higher than the preoperative heights. The average percentages of diseased vertebral heights to references at 1-year and 2-year after surgery were 72.0% and 86.0%, respectively. The average percentage of diseased vertebral heights to the references at 2-year after surgery was significantly higher than that of the historical cases at the same time. No minor or major adverse events were observed.

Conclusions

Transpedicular balloon kyphoplasty for the direct restoration of vertebrae plana seems feasible and safe in combination with short-term posterior instrumentation. Better short-time vertebrae remodeling was observed 2 years after surgery. Active surgical treatment is suggested for children who have vertebrae plana as a result of EG in order to maintain the ability to recover vertebral height.
Doxycycline attenuates l-DOPA-induced dyskinesia through an anti-inflammatory effect in a hemiparkinsonian mouse model
Authors: dos Santos Pereira Maurício , Nascimento Glauce Crivelaro do , Bortolanza Mariza , Michel Patrick Pierre , Raisman-Vozari Rita , Del Bel Elaine
Published: November 2022

The pharmacological manipulation of neuroinflammation appears to be a promising strategy to alleviate l-DOPA-induced dyskinesia (LID) in Parkinson’s disease (PD). Doxycycline (Doxy), a semisynthetic brain-penetrant tetracycline antibiotic having interesting anti-inflammatory properties, we addressed the possibility that this compound could resolve LID in l-DOPA-treated C57BL/6 mice presenting either moderate or intermediate lesions of the mesostriatal dopaminergic pathway generated by intrastriatal injections of 6-OHDA. Doxy, when given subcutaneously before l-DOPA at doses of 20 mg kg−1 and 40 mg kg−1, led to significant LID reduction in mice with moderate and intermediate dopaminergic lesions, respectively. Importantly, Doxy did not reduce locomotor activity improved by l-DOPA. To address the molecular mechanism of Doxy, we sacrificed mice with mild lesions 1) to perform the immunodetection of tyrosine hydroxylase (TH) and Fos-B and 2) to evaluate a panel of inflammation markers in the striatum, such as cyclooxygenase-2 and its downstream product Prostaglandin E2 along with the cytokines TNF-α, IL-1β and IL-6. TH-immunodetection revealed that vehicle and Doxy-treated mice had similar striatal lesions, excluding that LID improvement by Doxy could result from neurorestorative effects. Importantly, LID inhibition by Doxy was associated with decreased Fos-B and COX-2 expression and reduced levels of PGE2, TNF-α, and IL-1β in the dorsolateral striatum of dyskinetic mice. We conclude 1) that Doxy has the potential to prevent LID regardless of the intensity of dopaminergic lesioning and 2) that the anti-inflammatory effects of Doxy probably account for LID attenuation. Overall, the present results further indicate that Doxy might represent an attractive and alternative treatment for LID in PD.
Trust and communication in human-machine teaming
Authors: Ibrahim Memunat A. , Assaad Zena , Williams Elizabeth
Published: November 2022

Intelligent highly-automated systems (HASs) are increasingly being created and deployed at scale with a broad range of purposes and operational environments. In uncertain or safety-critical environments, HASs are frequently designed to seamlessly co-operate with humans, thus, forming human-machine teams (HMTs) to achieve collective goals. Trust plays an important role in this dynamic: humans need to be able to develop an appropriate level of trust in their HAS teammate(s) to form an HMT capable of safely and effectively working towards goal completion. Using Autonomous Ground Vehicles (AGVs) as an example of an HAS used in dynamic social contexts, we explore interdependent teaming and communication between humans and AGVs in different contexts and examine the role of trust and communication in these teams. Drawing on lessons from the AGV example for the design of an HAS used for an HMT more broadly, we argue that trust is experienced and built differently in different contexts, necessitating context-specific approaches to designing for trust in such systems.