Search

Abstract Vaccination against COVID-19 was integral to controlling the pandemic that persisted with the continuous emergence of SARS-CoV-2 variants. Using a mathematical model describing SARS-CoV-2 within-host infection dynamics, we estimate differences in virus and immunity due to factors of infecting variant, age, and vaccination history (vaccination brand, number of doses and time since vaccination). We fit our model in a Bayesian framework to upper respiratory tract viral load measurements obtained from cases of Delta and Omicron infections in Singapore, of whom the majority only had one nasopharyngeal swab measurement. With this dataset, we are able to recreate similar trends in URT virus dynamics observed in past within-host modelling studies fitted to longitudinal patient data. We found that Omicron had higher R0,within values than Delta, indicating greater initial cell-to-cell spread of infection within the host. Moreover, heterogeneities in infection dynamics across patient subgroups could be recreated by fitting immunity-related parameters as vaccination history-specific, with or without age modification. Our model results are consistent with the notion of immunosenescence in SARS-CoV-2 infection in elderly individuals, and the issue of waning immunity with increased time since last vaccination. Lastly, vaccination was not found to subdue virus dynamics in Omicron infections as well as it had for Delta infections. This study provides insight into the influence of vaccine-elicited immunity on SARS-CoV-2 within-host dynamics, and the interplay between age and vaccination history. Furthermore, it demonstrates the need to disentangle host factors and changes in pathogen to discern factors influencing virus dynamics. Finally, this work demonstrates a way forward in the study of within-host virus dynamics, by use of viral load datasets including a large number of patients without repeated measurements.

Volatile organic compounds (VOCs) affect secondary pollutant formation via active chemistry. Proton-transfer-reaction mass spectrometry (PTR-MS) is one of the most important techniques to study the highly variable spatial and temporal characteristics of VOCs. The response of protonated, adduct, and fragmented ions in PTR-MS in changing instrument settings and varying relative humidity (RH) requires rigorous characterization. Herein, we present dedicatedly designed laboratory experiments conducted to investigate the response of these ions for 21 VOCs, including 12 oxygenated VOCs and 2 nitriles, using the recently developed Vocus PTR-MS. Our results show that the focusing ion–molecule reactor (FIMR) axial voltage increases sensitivity by 3 to 4 orders of magnitude but does not significantly change the fractions of protonated ions. Reducing the FIMR pressure, however, substantially increases fragmentation. Applying a high radio frequency (RF) amplitude radially to the FIMR can enhance sensitivity by 1 to 2 orders of magnitude without affecting the protonated ion fractions. The change in big segmented quadrupole (BSQ) amplitude mainly affects sensitivity and protonated ion fraction by modifying ion transmission. The relationship between sensitivity and proton-transfer reaction rate constant is complicated by the influences from both ion transmission and protonated ion fraction. The protonated ions of most VOCs studied (19 out of 21) show less than 15 % variations in sensitivity as RH increases from ∼ 5% to ∼ 85 %, except for some long-chain aldehydes which show a positive RH variation of up to 30 %. Our results suggest that the Vocus PTR-MS can reliably quantify the majority of VOCs under ambient conditions with varying RH. However, caution is advised for small oxygenates such as formaldehyde and methanol due to their low sensitivity and for long-chain aldehydes due to their slight RH dependence and fragmentation.

Background: Sepsis is a severe and life-threatening condition triggered by a dysregulated response to infection, leading to organ failure and, often, death. The syndrome is expensive to treat, with survivors frequently experiencing reduced quality of life and enduring various long-term disabilities. The increasing understanding of RNA, RNA biology, and therapeutic potential offers an unprecedented opportunity to develop innovative therapy. Objective: This study is a scoping review focusing on pre-clinical studies of microRNA (miRNA)-based therapies for sepsis. Methodology: A scoping review. The search strategy identified papers published in PubMed until 15 October 2023, using the keywords (microRNA) AND (sepsis) AND (animal model). Inclusion criteria included papers that used either gain- or loss-of-function approaches, excluding papers that did not focus on microRNAs as therapy targets, did not include animal models, did not show organ failure-specific assessments, and focused on microRNAs as biomarkers. The PRISMA-ScR guideline was used in this study. Results: A total of 199 articles were identified that featured the terms “microRNA/miRNA/miR”, “Sepsis”, and “animal model”. Of these, 51 articles (25.6%) employed miRNA-based therapeutic interventions in animal models of sepsis. Of these, 15 studies extended their inquiry to include or reference human clinical data. Key microRNAs of interest and their putative mechanisms of action in sepsis are highlighted. Conclusions: The body of work examined herein predominantly addresses various dimensions of sepsis-induced organ dysfunction, supporting the emerging role of miRNAs as potential therapeutic candidates. However, nearly 5% of papers on miR-based therapy have been retracted over the past 5 years, raising important concerns regarding the quality and complexity of the biology and models for assessing therapeutic potential.

Abstract The scale and duration of neutralizing antibody responses targeting SARS-CoV-2 viral variants represents a critically important serological parameter that predicts protective immunity for COVID-19. In this study, we describe the development and employment of a new functional assay that measures neutralizing antibodies for SARS-CoV-2 and present longitudinal data illustrating the impact of age, sex and comorbidities on the kinetics and strength of vaccine-induced antibody responses for key variants in an Asian volunteer cohort. We also present an accurate quantitation of serological responses for SARS-CoV-2 that exploits a unique set of in-house, recombinant human monoclonal antibodies targeting the viral Spike and nucleocapsid proteins and demonstrate a reduction in neutralizing antibody titres across all groups 6 months post-vaccination. We also observe a marked reduction in the serological binding activity and neutralizing responses targeting recently newly emerged Omicron variants including XBB 1.5 and highlight a significant increase in cross-protective neutralizing antibody responses following a third dose (boost) of vaccine. These data illustrate how key virological factors such as immune escape mutations combined with host demographic factors such as age and sex of the vaccinated individual influence the strength and duration of cross-protective serological immunity for COVID-19.

BackgroundDigital health technologies have the potential to improve health outcomes for older adults, especially for those recovering from stroke. However, there are challenges to developing these technologies, such as data absenteeism (where older adults’ views are often underrepresented in research and development) and technology chauvinism (the belief that sophisticated technology alone is the panacea to addressing health problems), which hinder their effectiveness. ObjectiveIn this study, we aimed to address these challenges by developing a wearable glove integrated with culturally relevant exergames to motivate older adults to exercise and, for those recovering from stroke, to adhere to rehabilitation. MethodsWe conducted a moderated usability study with 19 older adults, of which 11 (58%) had a history of stroke. Our participants engaged in a 30-minute gameplay session with the wearable glove integrated with exergames, followed by a quantitative survey and an in-depth interview. We used descriptive analysis to compare responses to the System Usability Scale between those who had a history of stroke and those who did not. In addition, we analyzed the qualitative interviews using a bottom-up thematic analysis to identify key themes related to the motivations and barriers regarding the use of wearable gloves for rehabilitation and exercise. ResultsOur study generated several key insights. First, making the exergames exciting and challenging could improve exercise and rehabilitation motivation, but it could also have a boomerang effect, where participants may become demotivated if the games were very challenging. Second, the comfort and ease of use of the wearable gloves were important for older adults, regardless of their stroke history. Third, for older adults with a history of stroke, the functionality and purpose of the wearable glove were important in helping them with specific exercise movements. ConclusionsOur findings highlight the importance of providing contextual support for the effective use of digital technologies, particularly for older adults recovering from stroke. In addition to technology and usability factors, other contextual factors such as gamification and social support (from occupational therapists or caregivers) should be considered to provide a comprehensive approach to addressing health problems. To overcome data absenteeism and technology chauvinism, it is important to develop digital health technologies that are tailored to the needs of underserved communities. Our study provides valuable insights for the development of digital health technologies that can motivate older adults recovering from stroke to exercise and adhere to rehabilitation.

Introduction/Purpose: Acute ankle fractures are a common injury and represent a significant financial burden to the healthcare system. Reimbursement following ankle fractures is complicated by bundled payments within the 90-day global period which do not account for unpredictable complications. Comorbidity indices, such as the American Society of Anesthesiologists (ASA) classification, are often correlated with complications; however, the positive predictive value of these metrics have not been investigated. As insurers continue to transition towards bundled reimbursements, greater attentiveness towards providing efficient care is paramount. The purpose of this investigation is to develop a machine learning (ML) model that is predictive of complications following operative management of acute ankle fractures. This study will also compare ML algorithms to legacy indices to assess the predictive value in predicting complications. Methods: The American College of Surgeons-National Surgical Quality Improvement Program database was queried via Current Procedural Terminology (CPT) from 2015-2018 for open reduction internal fixation (ORIF) cases for ankle fractures, including ORIF of the medial malleolus, posterior malleolus, lateral malleolus, bimalleolar, trimalleolar, syndesmosis. Training and validation sets were created by randomly assigning 80% and 20% of the data set. Included variables were age, body mass index (BMI), operative time, smoking status, comorbidities, diagnosis, and preoperative hematocrit and albumin. Complications included any adverse event, transfusion, surgical site infection, return to the operating room, deep vein thrombosis or pulmonary embolism, pneumonia, urinary tract infection, cerebrovascular accident, cardiac arrest, myocardial infarction. Each ML algorithm was compared with one another and to a baseline model using American Society of Anesthesiologists (ASA) classification. Model strength was evaluated by calculating the area under the curve (AUC) for receiver operating characteristic (ROC) of any adverse event. Results: We identified a total of 28,736 ORIF cases. Mean age and BMI were 32.2 ± 18.6 years, 30.8 ± 7.6 kg/m^2, respectively. The overall incidence of any medical complication was 3.4% (n=975) with surgical site infection (1.3%, n=386) and return to operating room (1.3%, n=367) being the most common. Percentage hematocrit, BMI, operative time, and age were of highest importance in outcome prediction. Logistic regression (AUC: 72%) and gradient boosting (AUC: 72%) ML algorithms outperformed ASA classification (AUC: 69%) for predicting any adverse event following ORIF of ankle fractures. Conclusion: Legacy comorbidity indices are simple metrics that can be easily constructed from patient demographic variables and past medical history. However, the predictive power is limited as they have shown a low positive predictive value for predicting complications. Machine learning algorithms can calculate patient-specific risk for postoperative complications which may adjust perioperative care and site of surgery. These models have the capability to optimize utilization of healthcare resources and minimize excessive expenditure by providing patient-specific care. Receiver Operating Curve-Area under the Curve Analysis for Adverse Events Following ORIF of Ankle Fractures

Background: Total ankle arthroplasty (TAA), first developed as an alternative to ankle arthrodesis, has become an increasingly popular management option for end-stage ankle arthritis. Prior studies have shown commercial insurance payers base their coverage criteria on limited and low level of evidence research. This study aims to quantify and describe the evidence insurance companies use to support TAA coverage policies. Methods: The top 11 national commercial health insurance payers for TAA were identified. A google search was performed to identify payer coverage policies. Policy documents were examined and cited references were classified by type of reference as well as reviewed for level of evidence (LOE). Specific coverage criteria for each individual payer were then extracted. Criteria were compared to assess for similarities among commercial payers. Finally, all references cited by each payer were examined to determine whether they mentioned the specific payer criteria. Results: Six of the 11 payers had accessible coverage policies. The majority of cited references were primary journal articles (145, 60.9%) and the majority of references cited (179, 75.2%) were level III or level IV evidence. We found significant homogeneity in coverage criteria among payers. In addition, cited sources inconsistently mentioned specific payer coverage criteria. Conclusion: This study demonstrates that commercial insurance payers rely on the relatively low level of currently available scientific evidence when formulating coverage policies for TAA use and adopt criteria that have not been thoroughly analyzed in the literature. More high level of evidence research is needed to help clinicians and insurance companies further refine indications for TAA so that patients who might benefit from the procedure are adequately covered. Level of Evidence: Level IV, review.

Abstract Background Cancer predisposition is most often studied in the context of single cancers. However, inherited cancer predispositions can also give rise to multiple primary cancers. Yet, there is a paucity of studies on genetic predisposition in multiple primary cancers, especially those outside of well-defined cancer predisposition syndromes. This study aimed to identify germline variants associated with dual primary cancers of the breast and lung. Methods Exome sequencing was performed on germline DNA from 55 Singapore patients (52 [95%] never-smokers) with dual primaries in the breast and lung, confirmed by histopathology. Using two large control cohorts: the local SG10K_Health (n = 9770) and gnomAD non-cancer East Asians (n = 9626); and two additional local case cohorts of early-onset or familial breast cancer (n = 290), and lung cancer (n = 209), variants were assessed for pathogenicity in accordance with ACMG/AMP guidelines. In particular, comparisons were made with known pathogenic or likely pathogenic variants in the ClinVar database, pathogenicity predictions were obtained from in silico prediction software, and case–control association analyses were performed. Results Altogether, we identified 19 pathogenic or likely pathogenic variants from 16 genes, detected in 17 of 55 (31%) patients. Six of the 19 variants were identified using ClinVar, while 13 variants were classified pathogenic or likely pathogenic using ACMG/AMP guidelines. The 16 genes include well-known cancer predisposition genes such as BRCA2, TP53, and RAD51D; but also lesser known cancer genes EXT2, WWOX, GATA2, and GPC3. Most of these genes are involved in DNA damage repair, reaffirming the role of impaired DNA repair mechanisms in the development of multiple malignancies. These variants warrant further investigations in additional populations. Conclusions We have identified both known and novel variants significantly enriched in patients with primary breast and lung malignancies, expanding the body of known cancer predisposition variants for both breast and lung cancer. These variants are mostly from genes involved in DNA repair, affirming the role of impaired DNA repair in the predisposition and development of multiple cancers.

Background: Intra-amniotic inflammation (IAI) is associated with increased risk of preterm birth and bronchopulmonary dysplasia (BPD), but the mechanisms by which IAI leads to preterm birth and BPD are poorly understood, and there are no effective therapies for preterm birth and BPD. The transcription factor c-Myc regulates various biological processes like cell growth, apoptosis, and inflammation. We hypothesized that c-Myc modulates inflammation at the maternal-fetal interface, and neonatal lung remodeling. The objectives of our study were 1) to determine the kinetics of c-Myc in the placenta, fetal membranes and neonatal lungs exposed to IAI, and 2) to determine the role of c-Myc in modulating inflammation at the maternal-fetal interface, and neonatal lung remodeling induced by IAI.Methods: Pregnant Sprague-Dawley rats were randomized into three groups: 1) Intra-amniotic saline injections only (control), 2) Intra-amniotic lipopolysaccharide (LPS) injections only, and 3) Intra-amniotic LPS injections with c-Myc inhibitor 10058-F4. c-Myc expression, markers of inflammation, angiogenesis, immunohistochemistry, and transcriptomic analyses were performed on placenta and fetal membranes, and neonatal lungs to determine kinetics of c-Myc expression in response to IAI, and effects of prenatal systemic c-Myc inhibition on lung remodeling at postnatal day 14.Results: c-Myc was upregulated in the placenta, fetal membranes, and neonatal lungs exposed to IAI. IAI caused neutrophil infiltration and neutrophil extracellular trap (NET) formation in the placenta and fetal membranes, and neonatal lung remodeling with pulmonary hypertension consistent with a BPD phenotype. Prenatal inhibition of c-Myc with 10058-F4 in IAI decreased neutrophil infiltration and NET formation, and improved neonatal lung remodeling induced by LPS, with improved alveolarization, increased angiogenesis, and decreased pulmonary vascular remodeling.Discussion: In a rat model of IAI, c-Myc regulates neutrophil recruitment and NET formation in the placenta and fetal membranes. c-Myc also participates in neonatal lung remodeling induced by IAI. Further studies are needed to investigate c-Myc as a potential therapeutic target for IAI and IAI-associated BPD.

IntroductionPrevious research suggests that altered experiences of agency are an underlying vulnerability in both schizophrenia and autism. Here, we explore agency as a potential transdiagnostic factor by conducting a systematic review of existing literature investigating agency in autism and schizophrenia individually and together.MethodsFollowing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted three systematic searches on PsycINFO, Embase, Medline, PubMed and Web of Science to identify studies that investigated (1) agency in schizophrenia, (2) agency in autism, and (3) agency in both schizophrenia and autism.ResultsA total of 31 articles met eligibility criteria for inclusion and data extraction, with 24 measuring agency in schizophrenia, 7 investigating agency in autism, and no articles comparing the two. Results show that, compared to control populations, agency is significantly different in every identified schizophrenia study and generally not significantly different in autism.DiscussionImportantly, we identified a lack of studies using common tasks and a disproportionate number of studies investigating different dimensions of agency across the two conditions, resulting in limited grounds for valid comparison.Systematic review registrationProspero, CRD42021273373.

Ship-based multi-axis differential optical absorption spectroscopy (MAX-DOAS) measurements were conducted along the marginal seas of China from 19 April to 16 May 2018 to measure the vertical profiles of aerosol, nitrogen dioxide (NO2), and nitrous acid (HONO). Along the cruise route, we found five hot spots with enhanced tropospheric NO2 vertical column densities (VCDs) in the Yangtze River Delta, Taiwan Strait, Guangzhou–Hong Kong–Macau Greater Bay Area, port of Zhanjiang, and port of Qingdao. Enhanced HONO concentrations could usually be observed under high-level aerosol and NO2 conditions, whereas the reverse was not always the case. To understand the impacts of relative humidity (RH), temperature, and aerosol on the heterogeneous reaction of NO2 to form HONO in different scenarios, the Chinese Academy of Meteorological Sciences (CAMS) and Southern University of Science and Technology (SUST) MAX-DOAS stations were selected as the inland and coastal cases, respectively. The RH turning points in CAMS and SUST cases were both ∼ 65 % (60 %–70 %), whereas two turning peaks (∼ 60 % and ∼ 85 %) of RH were found in the sea cases. As temperature increased, the HONO / NO2 ratio decreased with peak values appearing at ∼ 12.5∘C in CAMS, whereas the HONO / NO2 gradually increased and reached peak values at ∼ 31.5∘C in SUST. In the sea cases, when the temperature exceeded 18.0∘C, the HONO / NO2 ratio rose with increasing temperature and achieved its peak at ∼ 25.0∘C. This indicated that high temperature can contribute to the secondary formation of HONO in the sea atmosphere. In the inland cases, the correlation analysis between HONO and aerosol in the near-surface layer showed that the ground surface is more crucial to the formation of HONO via the heterogeneous reaction of NO2; however, in the coastal and sea cases, the aerosol surface contributed more. Furthermore, we discovered that the conversion rate of NO2 to HONO through heterogeneous reactions in the sea cases is larger than that in the inland cases in higher atmospheric layers (> 600 m). Three typical events were selected to demonstrate three potential contributing factors of HONO production under marine conditions (i.e., transport, NO2 heterogeneous reaction, and unknown HONO source). This study elucidates the sea–land and vertical differences in the forming mechanism of HONO via the NO2 heterogeneous reaction and provides deep insights into tropospheric HONO distribution, transforming process, and environmental effects.

The molecular mechanisms underlying lymph-node metastasis in head and neck squamous-cell carcinoma remain to be investigated. Here, the authors perform single-cell RNA sequencing of cancer cells and CD8 + T cells and suggest potential mechanisms of immune evasion during early metastasis.

Pollutant transport has a substantial impact on the atmospheric environment in megacity clusters. However, owing to the lack of knowledge of vertical pollutant structure, quantification of transport processes and understanding of their impacts on the environment remain inadequate. In this study, we retrieved the vertical profiles of aerosols, nitrogen dioxide (NO2), and formaldehyde (HCHO) using multi-axis differential optical absorption spectroscopy (MAX-DOAS) and analyzed three typical transport phenomena over the North China Plain (NCP) and Yangtze River Delta (YRD). We found the following: (1) the main transport layers (MTL) of aerosols, NO2, and HCHO along the southwest–northeast transport pathway in the Jing-Jin-Ji region were approximately 400–800, 0–400, and 400–1200 m, respectively. The maximum transport flux of HCHO appeared in Wangdu (WD), and aerosol and NO2 transport fluxes were assumed to be high in Shijiazhuang (SJZ), both urban areas being significant sources feeding regional pollutant transport pathways. (2) The NCP was affected by severe dust transport on 15 March 2021. The airborne dust suppressed dissipation and boosted pollutant accumulation, decreasing the height of high-altitude pollutant peaks. Furthermore, the dust enhanced aerosol production and accumulation, weakening light intensity. For the NO2 levels, dust and aerosols had different effects. At the SJZ and Dongying (DY) stations, the decreased light intensity prevented NO2 photolysis and favored NO2 concentration increase. In contrast, dust and aerosols provided surfaces for heterogeneous reactions, resulting in reduced NO2 levels at the Nancheng (NC) and Xianghe (XH) stations. The reduced solar radiation favored local HCHO accumulation in SJZ owing to the dominant contribution of the primary HCHO. (3) Back-and-forth transboundary transport between the NCP and YRD was found. The YRD-to-NCP and NCP-to-YRD transport processes mainly occurred in the 500–1500 and 0–1000 m layers, respectively. This transport, accompanied by the dome effect of aerosols, produced a large-scale increase in PM2.5, further validating the haze-amplifying mechanism.

Time is a fundamental component of our lives. It is both objective, a structure outside of ourselves, and subjective, an element that is relative to the life we live and how we experience it. The disabled body must come to terms with time to understand the future impact of the injury and its progression, as well as how the injury will impose a new more accelerated aging process in the body, resulting in a compressed lifespan. The body also challenges time’s control of the body. This paper extends the literature on the study of time to the experience of adults aging with a spinal cord injury (SCI). Drawing from interviews conducted with adults with long-term SCI, it examines how their narratives about aging and the proactive management of their lives reflect their orientation toward and anticipation of the future. Recognizing that the spoken word often carries a multiplicity of meanings, it considers what participants’ words might imply about their engagement with time. The results of this study show that the process of aging is characterized by uncertainty and the expectations of functional and health decline, requiring a sense of urgency and vigilance in the face of the uncertain course of aging with SCI. Participants understood that their lifespan was compressed due to the physiological impact of accelerated aging. Knowledge of this compression made time a scarce resource. Yet, despite it being the arbiters of their futures, so too were they the arbiters of time.

Abstract Background Blastocystis is a common protistan parasite inhabiting the gastrointestinal tract of humans and animals. While there are increasing reports characterizing the associations between Blastocystis and the gut microbiome in healthy individuals, only a few studies have investigated the relationships between Blastocystis and the gut microbiota in diarrheal patients. Methods The effects of a specific subtype (ST7) of Blastocystis on the composition of gut microbiota in diarrheal patients were investigated using 16S ribosomal RNA (rRNA) gene sequencing and bioinformatic analyses. Results Compared with diarrheal patients without Blastocystis, diarrheal patients infected with Blastocystis ST7 exhibited lower bacterial diversity. Beta diversity analysis revealed significant differences in bacterial community structure between ST7-infected and Blastocystis-free patients. The proportion of Enterobacteriaceae and Escherichia-Shigella were significantly enriched in ST7-infected patients. In contrast, the abundance of Bacteroides and Parabacteroides were more prevalent in Blastocystis-free patients. Conclusions The results of this study revealed, for the first time, that infection with Blastocystis ST7 is associated with lower bacterial diversity and altered microbial structure in diarrheal patients. Our study on clinical diarrheal patients is also the first to reinforce the notion that ST7 is a pathogenic subtype of Blastocystis. Graphical Abstract

Bimetallic Ni-Cu catalysts supported on halloysite nanotubes with different metal contents (Hal-Ni80Cu20, Hal-Ni70Cu30, Hal-Ni42Cu58) were prepared and employed in the catalytic degradation of chitosan (CS). The relationship between catalytic performances of the catalysts with the different metal contents were studied. The highest catalytic activity was reported for Hal-Ni42Cu58 due to the higher proportion of the active Cu2+ in the catalytic degradation. Furthermore in Hal-Ni42Cu58, CuO persisted dominantly with Ni(OH)2 as compared to Hal-Ni80Cu20 where Cu(OH)2 was also available. Overall, the bimetallic-supported Hal catalysts displayed better catalytic activities than monometallic supported catalysts due to the synergistic effect between the metals.

The daily measurements of the disk-integrated solar radio flux, observed by the Radio Solar Telescope Network, at 245, 410, 610, 1415, 2695, 4995, and 8800 MHz during the time interval of 1989 January 1 to 2019 December 17, are used to investigate the temporal evolution of radial differential rotation of the solar corona using the methods of ensemble empirical mode decomposition (EEMD) and wavelet analysis. Overall, the results reveal that over the 30 yr period, the rotation rates for the observed solar radio flux within the frequency range of 245–8800 MHz show an increase with frequency. This verifies the existence of the radial differential rotation of the solar corona over long timescales of nearly three solar cycles. Based on the radio emission mechanism, to some extent, the results can also serve as an indicator of how the rotation of the solar upper atmosphere varies with altitude within a specific range. From the temporal variation of rotation cycle lengths of radio flux, the coronal rotation at different altitudes from the low corona to approximately 1.3 R _⊙ exhibits complex temporal variations with the progression of the solar cycle. However, in this altitude range, over the past 30 yr from 1989 to 2019, the coronal rotation consistently becomes gradually slower as the altitude increases. Finally, the EEMD method can extract rotation cycle signals from these highly randomized radio emissions, and so it can be used to investigate the rotation periods for the radio emissions at higher or lower frequencies.

Neutron-induced nuclear reactions play an important role in the Big Bang Nucleosynthesis. Their excitation functions are, from an experimental point of view, usually difficult to measure. Nevertheless, in the last decades, big efforts have led to a better understanding of their role in the primordial nucleosynthesis network. In this work, we apply the Trojan Horse Method to extract the cross section at astrophysical energies for the ^3 He(n,p) ^3 H reaction after a detailed study of the ^2 H( ^3 He,pt)H three-body process. Data extracted from the present measurement are compared with other published sets. The reaction rate is also calculated, and the impact on the Big Bang nucleosynthesis is examined in detail.

Intro: Recent reports have shown that antibiotics were commonly prescribed in COVID-19 designated hospitals throughout the pandemic in spite of it being ineffective in treating viruses such as SARS-COV 2 which is the pathogen responsible for causing COVID-19. Methods: We conducted a cross-sectional Point Prevalence Survey (PPS) involving all wards in Hospital Sungai Buloh. Each ward was audited within one day within the period of two weeks (1st December 2021 till 14th December 2021). All in-patients receiving IV or oral antibiotics at 8am on the day of survey were included in the study. Findings: A total of 200 out of 664 in-patients (30%) were treated with antibiotics during the study period. COVID ICU recorded the highest prevalence of patient on antibiotics (83%) followed by General Medical (43%). Majority of patients received antibiotics for empirical therapy (80%, 160/200) and community-acquired pneumonia was the most common indication documented (36.5%, 75/205), followed by hospital-acquired pneumonia, with 23.4% of total documented indication (48/205). We found that in half of the patients (104/200), clinicians did not document the indication of antibiotic. Rate of prescription that was compliant to guideline was higher than that of non-compliant to guideline from total of 139 cases recorded (68% vs 32%). We found that there was a significant association between rate of compliant to guideline with respiratory diseases (χ² = 5.37, p

Automated building footprints extraction from High Spatial Resolution (HSR) remote sensing images plays important roles in urban planning and management, and hazard and disease control. However, HSR images are not always available in practice. In these cases, super-resolution, especially deep learning (DL)-based methods, can provide higher spatial resolution images given lower resolution images. In a variety of remote sensing applications, DL based super-resolution methods are widely used. However, there are few studies focusing on the impact of DL-based super-resolution on building footprint extraction. As such, we present an exploration of this topic. Specifically, we first super-resolve the Massachusetts Building Dataset using bicubic interpolation, a pre-trained Super-Resolution CNN (SRCNN), a pre-trained Residual Channel Attention Network (RCAN), a pre-trained Residual Feature Aggregation Network (RFANet). Then, using the dataset under its original resolution, as well as the four different super-resolutions of the dataset, we employ the High-Resolution Network (HRNet) v2 to extract building footprints. Our experiments show that super-resolving either training or test datasets using the latest high-performance DL-based super-resolution method can improve the accuracy of building footprints extraction. Although SRCNN based building footprint extraction gives the highest Overall Accuracy, Intersection of Union and F1 score, we suggest using the latest super-resolution method to process images before building footprint extraction due to the fixed scale ratio of pre-trained SRCNN and low speed of convergence in training.

The nighttime light (NTL) remote sensed imagery has been applied in monitoring human activities from many perspectives. As the two most widely used NTL satellites, the Defense Meteorological Satellite Program (DMSP) Operational Linescan System and the Suomi National Polar-orbiting Partnership (NPP)-Visible Infrared Imaging Radiometer Suite (VIIRS) have different spatial and radiometric resolutions. Thus, some long-time series analysis cannot be conducted without effective and accurate cross-calibration of these two datasets. In this study, we proposed a deep-learning based model to simulate VIIRS-liked DMSP NTL data by integrating the enhanced vegetation index (EVI) data product from MODIS. By evaluating the spatial pattern of the results, the modified Self-Supervised Sparse-to-Dense networks delivered satisfying results of spatial resolution downscaling. The quantitative analysing of the simulated VIIRS-liked DMSP NTL with original VIIRS NTL showed a good consistency at the pixel level of four selected sub datasets with R2 ranging from 0.64 to 0.76, and RMSE ranging from 3.96-9.55. Our method presents that the deep learning model can learn from relatively raw data instead of fine processed data based on expert knowledge to cross-sensor calibration and simulation NTL data.

The outbreak of COVID-19 promoted strict restrictions to human activities in China, which led to a dramatic decrease in most air pollutant concentrations (e.g., PM2.5, PM10, NOx, SO2 and CO). However, an obvious increase in ozone (O3) concentrations was found during the lockdown period in most urban areas of China. In this study, we conducted field measurements targeting ozone and its key precursors by utilizing a novel proton transfer reaction time-of-flight mass spectrometer (PTR-TOF-MS) in Changzhou, which is representative of the Yangtze River Delta (YRD) city cluster of China. We further applied the integrated methodology including machine learning, an observation-based model (OBM) and sensitivity analysis to obtain insights into the reasons causing the obvious increase in ozone. Major findings include the following: (1) by deweathered calculation, we found changes in precursor emissions contributed 1.46 ppbv to the increase in the observed O3 during the full-lockdown period in 2020, while meteorology constrained 3.0 ppbv of O3 in the full-lockdown period of 2019. (2) By using an OBM, we found that although a significant reduction in O3 precursors was observed during the full-lockdown period, the photochemical formation of O3 was stronger than that during the pre-lockdown period. (3) The NOx/VOC ratio dropped dramatically from 1.84 during the pre-lockdown to 0.79 in the full-lockdown period, which switched O3 formation from a VOC-limited regime to the boundary of a NOx- and VOC-limited regime. Additionally, box model results suggested that the decrease in the NOx/VOC ratio during the full-lockdown period could increase the mean O3 by 2.4 ppbv. Results of this study give insights into the relationship between O3 and its precursors in urban area and demonstrate reasons for the obvious increase in O3 in most urban areas of China during the COVID-19 lockdown period. This study also underlines the necessity of controlling anthropogenic oxygenated volatile organic compounds (OVOCs), alkenes and aromatics in the sustained campaign of reducing O3 pollution in China.

Abstract Background Blastocystis ST4 is a common protistan parasite of the gastrointestinal tract of humans and a wide range of animals. While it has been suggested that colonization with ST4 is associated with healthy gut microbiota, how ST4 influences the gut microbiota remains poorly studied. This study aimed to examine the interactions between ST4 and several intestinal bacteria using in vitro co-culture systems, and to further investigate the mechanism of interaction and its effect on the epithelial barrier integrity of HT-29 cells. Methods Seven intestinal bacteria Bacteroides fragilis, Bifidobacterium longum, Bacillus subtilis, Bacteroides vulgatus, Escherichia coli, Enterococcus faecalis, and Lactobacillus brevis were co-cultured with Blastocystis ST4 in vitro. Flow cytometry and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) were used to determine the role of reactive oxygen species (ROS) and bacteria oxidoreductase genes, respectively, in response to Blastocystis co-incubation. Transepithelial electrical resistance (TEER) and flux assays were performed to assess the effect of microbiota representatives on the integrity of the intestinal epithelial barrier. Results Co-incubation with Blastocystis ST4 showed a beneficial influence on most intestinal bacteria, while ST4 significantly inhibited the growth of B. vulgatus, a common pathogen in the genus Bacteroides. The decrease in B. vulgatus when co-incubated with Blastocystis ST4 was associated with high levels of ROS and the upregulation of oxidative stress-related genes. Furthermore, co-incubation with Blastocystis ST4 was able to protect the intestinal epithelial barrier from damage by B. vulgatus. Conclusions This study demonstrated, for the first time, that Blastocystis ST4 has beneficial effects on intestinal commensal bacteria in vitro, and can inhibit the growth of pathogenic B. vulgatus. Combined with previous microbiome research on ST4, our data suggest that ST4 may be a beneficial commensal. Graphical Abstract

Despite frequent co-occurrence of drought and heat stress, the molecular mechanisms governing plant responses to these stresses in combination have not often been studied. This is particularly evident in non-model, perennial plants. We conducted large scale physiological and transcriptome analyses to identify genes and pathways associated with grapevine response to drought and/or heat stress during stress progression and recovery. We identified gene clusters with expression correlated to leaf temperature and water stress and five hub genes for the combined stress co-expression network. Several differentially expressed genes were common to the individual and combined stresses, but the majority were unique to the individual or combined stress treatments. These included heat-shock proteins, mitogen-activated kinases, sugar metabolizing enzymes, and transcription factors, while phenylpropanoid biosynthesis and histone modifying genes were unique to the combined stress treatment. Following physiological recovery, differentially expressed genes were found only in plants under heat stress, both alone and combined with drought. Taken collectively, our results suggest that the effect of the combined stress on physiology and gene expression is more severe than that of individual stresses, but not simply additive, and that epigenetic chromatin modifications may play an important role in grapevine responses to combined drought and heat stress.

BackgroundThe validated Incremental Shuttle Walk Test (ISWT) is widely used for evaluating maximal exercise capacity, with the distance-walked (IWSD) as the primary outcome. However, there are no normative reference values (NRV) and reference equations to predict ISWD for the Singaporean population.ObjectivesThis study aims to establish the NRV and reference equations for ISWD in healthy Singaporeans aged 21 to 80 and investigate the determining variables during ISWT.MethodsThis cross-sectional study recruited community-dwelling healthy subjects aged 21-80 from the community via convenience sampling. Each subject completed two trials of the ISWT according to the standard protocol. Variables measured during the trials included ISWD, pre-and post-test heart rate (HR), oxygen saturation, blood pressure (BP), modified Borg's dyspnoea score and Borg's rate of perceived exertion (RPE).Results199 healthy Singaporean (females = 114, males = 85) participated in the study. The overall median ISWD was 660.0 metres (m) [interquartile range (IQR):440.0-850.0]. The age-stratified mean ISWD ranged from 430.0 m (IQR:350.0-450.0) (aged 60-80) to 480.0 m (IQR:438.0-650.0) (aged 40-59) to 780.0 m (IQR:670.0-960.0) (aged 21-39). Gender, age, weight, height and HR change (highest post-test HR minus pre-test HR) were the most significant variables (p < 0.001). IWSD (m) = 651.4(Height, m) +89.7(Gender, male = 1; female = 0) -6.31(Age, years) -3.61(Weight, kilograms) +2.54(HR change, beats per minute); R2 = 0.741. Previously published ISWT reference equations cannot accurately predict the ISWD in the Singaporean population.ConclusionsThis study investigated the ISWD NRV and established reference equations for healthy Singaporeans aged 21-80. The information would be beneficial in setting performance benchmarks to guide physical assessment, intervention and rehabilitation.

BackgroundMany artificial intelligence (AI) studies have focused on development of AI models, novel techniques, and reporting guidelines. However, little is understood about clinicians' perspectives of AI applications in medical fields including ophthalmology, particularly in light of recent regulatory guidelines. The aim for this study was to evaluate the perspectives of ophthalmologists regarding AI in 4 major eye conditions: diabetic retinopathy (DR), glaucoma, age-related macular degeneration (AMD) and cataract.MethodsThis was a multi-national survey of ophthalmologists between March 1st, 2020 to February 29th, 2021 disseminated via the major global ophthalmology societies. The survey was designed based on microsystem, mesosystem and macrosystem questions, and the software as a medical device (SaMD) regulatory framework chaired by the Food and Drug Administration (FDA). Factors associated with AI adoption for ophthalmology analyzed with multivariable logistic regression random forest machine learning.ResultsOne thousand one hundred seventy-six ophthalmologists from 70 countries participated with a response rate ranging from 78.8 to 85.8% per question. Ophthalmologists were more willing to use AI as clinical assistive tools (88.1%, n = 890/1,010) especially those with over 20 years' experience (OR 3.70, 95% CI: 1.10–12.5, p = 0.035), as compared to clinical decision support tools (78.8%, n = 796/1,010) or diagnostic tools (64.5%, n = 651). A majority of Ophthalmologists felt that AI is most relevant to DR (78.2%), followed by glaucoma (70.7%), AMD (66.8%), and cataract (51.4%) detection. Many participants were confident their roles will not be replaced (68.2%, n = 632/927), and felt COVID-19 catalyzed willingness to adopt AI (80.9%, n = 750/927). Common barriers to implementation include medical liability from errors (72.5%, n = 672/927) whereas enablers include improving access (94.5%, n = 876/927). Machine learning modeling predicted acceptance from participant demographics with moderate to high accuracy, and area under the receiver operating curves of 0.63–0.83.ConclusionOphthalmologists are receptive to adopting AI as assistive tools for DR, glaucoma, and AMD. Furthermore, ML is a useful method that can be applied to evaluate predictive factors on clinical qualitative questionnaires. This study outlines actionable insights for future research and facilitation interventions to drive adoption and operationalization of AI tools for Ophthalmology.

Aeolus wind products became available to the public on 12 May 2020. In this study, Aeolus wind observations, L-band radiosonde (RS) data, and the European Centre for Medium-Range Weather Forecasts fifth-generation atmospheric reanalysis (ERA5) data were used to analyze the seasonality of Aeolus wind product performance over China. Based on the Rayleigh-clear and Mie-cloudy data, the data quality of the Aeolus effective detection data was verified, and the results showed that the Aeolus data were in good agreement with the L-band RS and ERA5 data. The Aeolus data relative errors in the four regions (Chifeng, Baoshan, Shapingba, and Qingyuan) in China were calculated based on different months (July to December 2019 and May to October 2020). The relative error in the Rayleigh-clear data in summer was significantly higher than that in winter, with the mean relative error parameter in July 174 % higher than that in December. The mean random error increased by 0.97 m s−1 in July compared with December, which also supported this conclusion. In addition, the distribution of the wind direction and high-altitude clouds in different months (July and December) was analyzed. The results showed that the distribution of the angle between the horizontal wind direction of the atmosphere and the horizontal line of sight had a greater proportion in the high error interval (70–110∘) in summer, and this proportion was 8.14 % higher in July than in December. The cloud top height in summer was approximately 3–5 km higher than that in winter, which might decrease the signal-to-noise ratio of Aeolus. Therefore, the wind product performance of Aeolus was affected by seasonal factors, which might be caused by seasonal changes in wind direction and cloud distribution.

Abstract Background Retinal regenerative therapies hold great promise for the treatment of inherited retinal degenerations (IRDs). Studies in preclinical lower mammal models of IRDs have suggested visual improvement following retinal photoreceptor precursors transplantation, but there is limited evidence on the ability of these transplants to rescue retinal damage in higher mammals. The purpose of this study was to evaluate the therapeutic potential of photoreceptor precursors derived from clinically compliant induced pluripotent stem cells (iPSCs). Methods Photoreceptor precursors were sub-retinally transplanted into non-human primates (Macaca fascicularis). The cells were transplanted both in naïve and cobalt chloride-induced retinal degeneration models who had been receiving systemic immunosuppression for one week prior to the procedure. Optical coherence tomography, fundus autofluorescence imaging, electroretinography, ex vivo histology and immunofluorescence staining were used to evaluate retinal structure, function and survival of transplanted cells. Results There were no adverse effects of iPSC-derived photoreceptor precursors on retinal structure or function in naïve NHP models, indicating good biocompatibility. In addition, photoreceptor precursors injected into cobalt chloride-induced retinal degeneration NHP models demonstrated an ability both to survive and to mature into cone photoreceptors at 3 months post-transplant. Optical coherence tomography showed restoration of retinal ellipsoid zone post-transplantation. Conclusions These findings demonstrate the safety and therapeutic potential of clinically compliant iPSC-derived photoreceptor precursors as a cell replacement source for future clinical trials.

The aerosol scattering coefficient is an essential parameter for estimating aerosol direct radiative forcing and can be measured by nephelometers. Nephelometers are problematic due to small errors of nonideal Lambetian light source and angle truncation. Hence, the observed raw scattering coefficient data need to be corrected. In this study, based on the random forest machine learning model and taking Aurora 3000 as an example, we have proposed a new method to correct the scattering coefficient measurements of a three-wavelength nephelometer under different relative humidity conditions. The result shows that the empirical corrected values match Mie-calculation values very well at all three wavelengths and under all of the measured relative humidity conditions, with more than 85 % of the corrected values having less than 2 % error. The correction method obtains a scattering coefficient with high accuracy and there is no need for additional observation data.

Abstract Background Human pluripotent stem cells (hPSCs) provide a promising cell source for retinal cell replacement therapy but often lack standardized cell production and live-cell shipment logistics as well as rigorous analyses of surgical procedures for cell transplantation in the delicate macula area. We have previously established a xeno- and feeder cell-free production system for hPSC differentiated retinal pigment epithelial (RPE) cells, and herein, a novel immunosuppressed non-human primate (NHP) model with a disrupted ocular immune privilege is presented for transplanting human embryonic stem cell (hESC)-derived RPE on a scaffold, and the safety and submacular graft integration are assessed. Furthermore, the feasibility of intercontinental shipment of live hESC-RPE is examined. Methods Cynomolgus monkeys were systemically immunosuppressed and implanted with a hESC-RPE monolayer on a permeable polyester-terephthalate (PET) scaffold. Microscope-integrated intraoperative optical coherence tomography (miOCT)-guided surgery, postoperative follow-up incorporated scanning laser ophthalmoscopy, spectral domain (SD-) OCT, and full-field electroretinography (ERG) were used as outcome measures. In addition, histology was performed after a 28-day follow-up. Results Intercontinental cell shipment, which took >30 h from the manufacturing to the transplantation site, did not alter the hESC-RPE quality. The submacular hESC-RPE xenotransplantation was performed in 11 macaques. The miOCT typically revealed foveal disruption. ERG showed amplitude and peak time preservation in cases with favorable surgical outcomes. Histology confirmed photoreceptor preservation above the grafts and in vivo phagocytosis by hESC-RPE, albeit evidence of cytoplasmic redistribution of opsin in photoreceptors and glia hypertrophy. The immunosuppression protocol efficiently suppressed retinal T cell infiltration and microglia activation. Conclusion These results suggest both structural and functional submacular integrations of hESC-RPE xenografts. It is anticipated that surgical technique refinement will further improve the engraftment of macular cell therapeutics with significant translational relevance to improve future clinical trials.

Routine pavement inspection is crucial to keep roads safe and reduce traffic accidents. However, traditional practices in pavement inspection are labour-intensive and time-consuming. Mobile laser scanning (MLS) has proven a rapid way for collecting a large number of highly dense point clouds covering roadway surfaces. Handling a huge amount of unstructured point clouds is still a very challenging task. In this paper, we propose an effective approach for pavement crack detection using MLS point clouds. Road surface points are first converted into intensity images to improve processing efficiency. Then, a Capsule Neural Network (CapsNet) is developed to classify the road points for pavement crack detection. Quantitative evaluation results showed that our method achieved the recall, precision, and F1-score of 95.3%, 81.1%, and 88.2% in the testing scene, respectively, which demonstrated the proposed CapsNet framework can accurately and robustly detect pavement cracks in complex urban road environments.

ABSTRACT Blastocystis is a common protistan parasite inhabiting the gastrointestinal tract of a wide range of hosts including humans and domestic and wild animals. Many studies have revealed the associations between Blastocystis and gut microbiome in humans. However, only a few studies have focused on the associations between Blastocystis and gut microbiome of animals, especially in forest musk deer (Moschus berezovskii). We investigated the effects of the Blastocystis colonization on the intestinal bacterial community compositions using amplicon sequencing targeting the V4 variable region of the 16S rRNA. Two subtypes of Blastocystis (ST5 and ST10) and Blastocystis-free (control) were included in this study. We found that compared with the forest musk deer without Blastocystis, ST10-colonized forest musk deer had higher bacterial richness and diversity, while ST5-colonized forest musk deer showed a comparable bacterial diversity. Likewise, beta diversity revealed significant differences in bacterial community structure between ST10-colonized and Blastocystis-free forest musk deer. The proportion of Bacteroidetes were significantly enriched in ST10-colonized forest musk deer. Bacterial community structure between ST5-colonized and Blastocystis-free forest musk deer did not differ significantly. The present study explored the associations between Blastocystis and gut microbial community of forest musk deer for the first time, and revealed ST10 colonization, instead of ST5, is associated with higher bacterial diversity and shifted microbial structure. Our data provides valuable insights into the associations between gut microbiomes and parasites. IMPORTANCE Forest musk deer is listed as an endangered species by International Union for Conservation of Nature Red List, and the Chinese government has introduced captivity breeding measures to curb the rapid decline of the musk deer population since the 1950s. It has been suggested that Blastocystis colonization can modulate the composition of the host's intestinal microbiota, thereby affecting the host health. The present study investigated the effects of the Blastocystis colonization on the gut microbiota in the feces of forest musk deer in Sichuan Province, China. Two subtypes (ST5 and ST10) have differential effects on the bacterial diversity and community composition, suggesting that the study of Blastocystis should be distinguished at the subtype level. Because the pathogenicity of Blastocystis is controversial, pathogenic, or commensal, continuous monitoring of the impact of Blastocystis colonization on the intestinal microbiota is of great significance to assess its health effects on forest musk deer.

Abstract Background Blastocystis is a common anaerobic colonic protist in humans with controversial pathogenicity. Clostridium difficile (C. difficile) is the commonest cause of infectious diarrhea in healthcare settings. The prevalence and subtype (ST) characteristics of Blastocystis in patients with C. difficile infection (CDI) are rarely documented. Therefore, the present study was conducted to investigate the prevalence and subtype characteristics of Blastocystis in patients with suspicion of CDI in Singapore. Methods Fecal samples were collected from 248 patients presenting with suspected CDI from a single tertiary hospital in Singapore. C. difficile was diagnosed through positive glutamate dehydrogenase (GDH) with or without toxin A/B using enzyme immunoassay methods. The prevalence and subtype genetic characteristics of Blastocystis were determined by polymerase chain reaction (PCR) amplification and analysis of the barcode region of the SSU rRNA gene. Results The proportion of C. difficile in patients with healthcare-associated diarrhea in this study was 44% (109/248). Among the 109 C. difficile-positive patients, 59 (54.1%, 59/109) tested positive for toxigenic C. difficile, which was considered CDI. Based on the sequence analyses of the barcode region of the SSU rRNA gene, 10.1% (25/248) of the patients were found to be Blastocystis-positive, and three subtypes were identified: ST7 (64%, 16/25), ST1 (20%, 5/25), and ST3 (16%, 4/25). Remarkably, we found five patients with Blastocystis and C. difficile coinfection, and further subtype analysis showed two with ST7, two with ST1, and one with ST3. Conclusions To the best of our knowledge, this is the first study to investigate the subtype distributions of Blastocystis in patients with CDI in Singapore. We found ST7 to be the predominant subtype in diarrheal patients. The pathogenicity of ST7 has been strongly suggested in previous in vitro and mouse model experiments, further confirming its potential pathogenicity to humans.

Background. Gout is frequently accompanied by hypertension, obesity, and/or impaired glucose tolerance, which are often complicated with heavy smoking and dietary violations, especially in male patients.Objective. To determine the behavioral characteristics of gout patients that could impact the results of urate lowering therapy.Subjects and methods. The relationship between behavioral characteristics and results of urate lowering therapy were investigated in 74 male gout patients of Chengdu Rheumatism Hospital. The results of treatment were evaluated using serum uric acid contents before and after treatment, VAS pain score before and after treatment. Behavioral characteristics for the last ten years (smoking status, daily volume of drinking water, etc.) were accessed by means of retrospective survey.Results. In gout patients with poor treatment response, serum uric acid at the beginning of the treatment was already significantly lower (365.76 ± 163.06 μmol/L); this trend was also noted in a “slow progress” group, while patients with higher serum uric acid before treatment had notably better response to urate lowering therapy. During further analysis age negatively correlated with serum uric acid (r = –0.328; p = 0.002) and uric acid clearance ratio (r = –0.299; p = 0.002).In patients with uric acid clearance ratio above 40 % the prevalence of kidney diseases (stones or dysfunction) was significantly lower compared to other groups. There was no significant influence of hypertension, diabetes mellitus, fatty liver or hyperlipidaemia on uric acid clearance ratio (p > 0.05).Amount of drinking water also influenced the serum uric acid clearance ratio. Bigger amount of patients in the “fast progress” group (40.0 % compared to 30.44 and 25.0 %) tended to drink more water.Conclusion. In most gout patients, serum uric acid levels before treatment acted as the reliable predictor of good response to urate lowering therapy. Treatment response (serum uric acid clearance ratio) correlated positively with the hyperuricemia and drinking sufficient amounts of water, negatively – with prolonged smoking (more than 10 years) and age.

Abstract The objective was to examine prospectively the association between retinal microvascular signs and development of diabetic kidney disease (DKD) in Asian and White populations. We analysed two population-based cohorts, composing of 1,221 Asians (SEED) and 703 White (WESDR) adults with diabetes. Retinal microvascular signs at baseline included vascular caliber (arteriolar—CRAE, and venular—CRVE) and diabetic retinopathy (DR). Incident cases of DKD were identified after ~ 6-year. Incident cases were defined based on eGFR in SEED and proteinuria or history of renal dialysis in WESDR. The incidence of DKD were 11.8% in SEED and 14.0% in WESDR. Wider CRAE in SEED (OR = 1.58 [1.02, 2.45]) and wider CRVE (OR = 1.69 [1.02, 2.80)) in WESDR were associated with increased risk of DKD. Presence of DR was associated with an increased risk of DKD in both cohorts (SEED: OR = 1.91 [1.21, 3.01] in SEED, WESDR: OR = 1.99 [1.18, 3.35]). Adding DR and retinal vascular calibers in the model beyond traditional risk factors led to an improvement of predictive performance of DKD risk between 1.1 and 2.4%; and improved classification (NRI 3 between 9%). Microvascular changes in the retina are longitudinally associated with risk of DKD.

Indirect ophthalmoscopy and handheld retinal imaging are the most common and traditional modalities for the evaluation and documentation of the pediatric fundus, especially for pre-verbal children. Optical coherence tomography (OCT) allows for in vivo visualization that resembles histology, and optical coherence tomography angiography (OCTA) allows for non-invasive depth-resolved imaging of the retinal vasculature. Both OCT and OCTA were extensively used and studied in adults, but not in children. The advent of prototype handheld OCT and OCTA have allowed for detailed imaging in younger infants and even neonates in the neonatal care intensive unit with retinopathy of prematurity (ROP). In this review, we discuss the use of OCTA and OCTA in various pediatric retinal diseases, including ROP, familial exudative vitreoretinopathy (FEVR), Coats disease and other less common diseases. For example, handheld portable OCT was shown to detect subclinical macular edema and incomplete foveal development in ROP, as well as subretinal exudation and fibrosis in Coats disease. Some challenges in the pediatric age group include the lack of a normative database and the difficulty in image registration for longitudinal comparison. We believe that technological improvements in the use of OCT and OCTA will improve our understanding and care of pediatric retina patients in the future.

Close-to-nature management (CTNM) has been proposed as a promising forestry management approach to improve the structure and quality of forests, which integrates wood production and ecological service functions. Research on the effect of CTNM on the univariate and bivariate distribution of the spatial structure of forest stands provides a scientific basis for the evaluation of CTNM implemented in forestry. Here, we analyzed and compared the spatial-structure characteristics of Masson pine (Pinus massoniana) plantations (young, middle-age, and near-mature stages) under CTNM 8 years after selective cutting and unmanaged control. We used univariate and bivariate distribution of three spatial-structure parameters: mingling (M), dominance (U), and uniform-angle index (W). Results showed that the effect of CTNM on spatial structure was more remarkable in middle-aged and near-mature Masson pine forests compared with the young forest. CTNM significantly improved mingling degree and promoted the horizontal distribution, thereby changing from a cluster to a random distribution. Moreover, CTNM improved the proportion of trees with a high mixing degree and random distribution and the proportion of trees having a micro-structure of random distribution with a high degree of mixture and dominance with a high degree of mixture in middle-aged and near-mature Masson pine forest. Overall, the implementation of CTNM 8 years ago showed a positive effect on the improvement of the spatial structure of Masson pine forest, but the present spatial structure is suboptimal. Further implementation of CTNM to adjust the mingling and uniform-angle index is necessary, and CTNM according to this method of frequency distribution of stand structure parameters can improve the success of forest management.

Atmospheric black carbon (BC) is the strongest solar radiative absorber in the atmosphere, exerting significant influences on the earth's radiation budget. The mass absorption cross section (MAC) is a crucial parameter for converting the light absorption coefficient (σab) to the equivalent BC mass concentration (EBC). Traditional filter-based instruments, such as the AE33, use a constant MAC of 7.77 m2/g at 880 nm to derive the EBC, which may lead to uncertainty in the EBC. In this paper, a new method of converting σab to the EBC is proposed by incorporating the variations of the MAC attributed to the influences of the aerosol coating state. A Mie simulation showed that the MAC varied dramatically with different core sizes and shell thicknesses. We compared our new method with the traditional method during a field measurement at a site on the North China Plain. The results showed that the MAC at 880 nm was smaller (larger) than 7.77 m2/g for particles smaller (larger) than 280 nm, resulting in an EBC mass size distribution derived from the new method that was higher (lower) than the traditional method for particles smaller (larger) than 280 nm. The size-integrated EBC derived from the new method was 16 % higher than that derived from the traditional method. Sensitivity analysis indicated that the uncertainty in the EBC caused by the refractive index (RI) was within 35 %, and the imaginary part of the RI had dominant influence on the derived EBC. This study emphasizes the necessity to take variations of the MAC into account when deriving the EBC from σab and can help constrain the uncertainty in EBC measurements.

Abstract Up-regulation of long non-coding RNAs (lncRNAs), colon-cancer associated transcript (CCAT) 1 and 2, was associated with worse prognosis in colorectal cancer (CRC). Nevertheless, their role in predicting metastasis in early-stage CRC is unclear. We measured the expression of CCAT1, CCAT2 and their oncotarget, c-Myc, in 150 matched mucosa-tumour samples of early-stage microsatellite-stable Chinese CRC patients with definitive metastasis status by multiplex real-time RT-PCR assay. Expression of CCAT1, CCAT2 and c-Myc were significantly up-regulated in the tumours compared to matched mucosa (p

Persistent wintertime heavy haze incidents caused by anthropogenic aerosols have repeatedly shrouded North China in recent years, while natural dust from the west and northwest of China also frequently affects air quality in this region. Through continuous observation by a multi-wavelength Raman lidar, here we found that wintertime aerosols in North China are typically characterized by a pronounced vertical stratification, where scattering nonspherical particles (dust or mixtures of dust and anthropogenic aerosols) dominated above the planetary boundary layer (PBL), and absorbing spherical particles (anthropogenic aerosols) prevailed within the PBL. This stratification is governed by meteorological conditions that strong northwesterly winds usually prevailed in the lower free troposphere, and southerly winds dominated in the PBL, producing persistent and intense haze pollution. With the increased contribution of elevated dust to the upper aerosols, the proportion of aerosol and trace gas at the surface in the whole column increased. Model results show that, besides directly deteriorating air quality, the key role of the elevated dust is to depress the development of PBL and weaken the turbulent exchange, mostly by lower level cooling and upper level heating, and it is more obvious during the dissipation stage, thus inhibiting the dissipation of heavy surface anthropogenic aerosols. The interactions of natural dust and anthropogenic aerosols under the unique topography of North China increase the surface anthropogenic aerosols and precursor gases, which may be one of the reasons why haze pollution in North China is heavier than that in other heavily polluted areas in China.

Abstract Deep learning (DL) has been shown to be effective in developing diabetic retinopathy (DR) algorithms, possibly tackling financial and manpower challenges hindering implementation of DR screening. However, our systematic review of the literature reveals few studies studied the impact of different factors on these DL algorithms, that are important for clinical deployment in real-world settings. Using 455,491 retinal images, we evaluated two technical and three image-related factors in detection of referable DR. For technical factors, the performances of four DL models (VGGNet, ResNet, DenseNet, Ensemble) and two computational frameworks (Caffe, TensorFlow) were evaluated while for image-related factors, we evaluated image compression levels (reducing image size, 350, 300, 250, 200, 150 KB), number of fields (7-field, 2-field, 1-field) and media clarity (pseudophakic vs phakic). In detection of referable DR, four DL models showed comparable diagnostic performance (AUC 0.936-0.944). To develop the VGGNet model, two computational frameworks had similar AUC (0.936). The DL performance dropped when image size decreased below 250 KB (AUC 0.936, 0.900, p