Long-term data are crucial for understanding ecological responses to climate and land use change; they are also vital evidence for informing management. As a migratory fish, Atlantic salmon are sentinels of both global and local environmental change. This paper reviews the main insights from six decades of research in an upland Scottish stream (Girnock Burn) inhabited by a spring Atlantic salmon population dominated by multi-sea-winter fish. Research began in the 1960s providing a census of returning adults, juvenile emigrants and in-stream production of Atlantic salmon. Early research pioneered new monitoring techniques providing new insights into salmon ecology and population dynamics. These studies underlined the need for interdisciplinary approaches for understanding salmon interactions with physical, chemical and biological components of in-stream habitats at different life-stages. This highlighted variations in catchment-scale hydroclimate, hydrology, geomorphology and hydrochemistry as essential to understanding freshwater habitats in the wider landscape context. Evolution of research has resulted in a remarkable catalogue of novel findings underlining the value of long-term data that increases with time as modelling tools advance to leverage more insights from “big data”. Data are available on fish numbers, sizes and ages across multiple life stages, extending over many decades and covering a wide range of stock levels. Combined with an unusually detailed characterisation of the environment, these data have enabled a unique process-based understanding of the controls and bottlenecks on salmon population dynamics across the entire lifecycle and the consequences of declining marine survival and ova deposition. Such powerful datasets, methodological enhancements and the resulting process understanding have informed and supported the development of fish population assessment tools which have been applied to aid management of threatened salmon stocks at large-catchment, regional and national scales. Many pioneering monitoring and modelling approaches developed have been applied internationally. This history shows the importance of integrating curiosity-driven science with monitoring for informing policy development and assessing efficacy of management options. It also demonstrates the need of continue to resource long-term sites which act as a focus for inter-disciplinary research and innovation, and where the overall value of the research greatly exceeds the costs of individual component parts.
Half of patients with renal cell carcinoma (RCC) will develop metastases. The disease is likely to be curable at early stages but incurable when metastatic. New and non-invasive biomarkers are needed for the diagnosis of RCC. Extracellular vesicles (EVs) are considered promising new biomarker targets for the diagnosis of various diseases. Our study aimed to develop an EV-based assay for the detection of RCC using a highly sensitive nanoparticle-aided time-resolved fluorescence immunoassay (NP-TRFIA). To confirm that the tetraspanins were located on EVs, we used size exclusion chromatography to separate EV- and PE (protein-enriched)-fractions from RCC4 and 786-O RCC cancer cell lines and HEK293. EV- and PE-fractions were quantified using NP-TRFIA assays established for tetraspanins CD9, CD63, CD81, and CD151. Tetraspanin biomarkers were further measured from RCC cell culture medium as well as serum samples of RCC (n=14), benign (n=17), and healthy (n=9) individuals. Among the tetraspanins, CD63 showed 3-5-fold higher expression on EVs derived from RCC4 and 786-O cell lines compared to those from the HEK293. A sandwich CD63-CD63 assay demonstrated significant discrimination of RCC patients from benign (p=0.0003), and healthy (p= 0.005) individuals, respectively. Similarly, the CD81-CD81 assay also enabled significant separation of RCC patients compared to benign (p=0.014), and healthy (p= 0.003) controls, respectively. This result suggests that RCC cell lines and serum of RCC patients show higher amounts of CD63- and CD81-enriched EVs compared to controls. Detection of these tetraspanin-enriched EVs using our NP-TRFIA approach may play a vital role in the detection of RCC.
This paper aims to solve the problem of accurately estimating flow duration curves (FDC) in catchments lacking diachronic flow data. Based on 645 sets of observed data in the middle and lower reaches of the Yangtze River (YZR), which include 22 basin characteristic variables, eight machine learning (ML) models (SVM, RF, BPNN, ELM, XGB, RBF, PSO-BP, GWO-BP) were integrated to predict the FDC (quantiles of flow rate corresponding to 15 exceedance probabilities were studied), after which the model most suitable for predicting was determined. Finally, the SHapley Additive exPlanation (SHAP) method was used to determine and quantify the impact of various input variables on different quantiles and the degree of that influence. Results indicate that: (1) The GWO-BP model is the best ML model for predicting FDC among the eight, having good prediction performances throughout the entire duration with determination coefficients (R2) on the testing set of 0.86 to 0.94 and Nash-Sutcliff criterion (NSE) of 0.78 to 0.94. (2) The ML model (BPNN) optimized using swarm intelligence can effectively predict FDC. (3) The predictive impact of variables on different quantiles varies, with and BFI_mean contributes significantly to predicting FDC. The former has a negative effect on the prediction result and has better contribution to predicting higher flow rate (i.e., having higher accuracy in predicting the upper tail of FDC), whereas the latter is the opposite. SHAP’s explanations are consistent with the physical model, revealing local interactions between predictive factors. The results demonstrate that the method proposed in this paper can greatly improve the prediction accuracy and is innovative and valuable in model interpretation and factor selection.
Dilemma of seronegative lupus nephritis: A case report of diffuse proliferative glomerulonephritis with thrombotic microangiopathyYuxuan Wu1, Qiaoyu Wang1, Haiyan Zhang2, Jianhua Qin1*, Weihua Wu1*1Department of Nephrology,Affiliated Hospital of Southwest Medical University; Sichuan Clinical Research Center for Nephropathy; Metabolic Vascular Disease Key Laboratory, Luzhou, Sichuan, China
The fertile Anatolian lands in Turkey, supporting about 80 million people, rely on abundant water resources. The Kızılırmak River basin in Anatolia is vulnerable to global warming, mainly due to snowmelt in its headwaters. Quantifying the upper watershed’s climate sensitivity is crucial for assessing water availability. Instead of using Global Climate Model (GCM)-driven projections, a sensitivity-based approach was employed with the Variable Infiltration Capacity (VIC) hydrologic model to assess the region’s hydrological vulnerability to potential future climatic changes. Considering the consistent projections of increasing temperature (T) over this region in GCMs, the system was perturbed to examine gradients of a more challenging climate, characterized by warming and drying conditions. The sensitivity of streamflow, snowpack water equivalence, and evapotranspiration to T and Precipitation (P) variations under each perturbation or “reference” climates was quantified. Results indicate that streamflow responds to T negatively under all warming scenarios. Streamflow responding to P increases nonlinearly as P decreases in the reference climates. These results suggest that there will be heightened difficulty in managing water resources in the region if it undergoes both warming and drying due to the following setbacks: 1) water availability will shift away from the summer season of peak water demand due to the warming effects on the snowpack, 2) annual water availability will likely decrease due to a combination of warming and lower precipitation, and 3) streamflow sensitivity to hydroclimatic variability will increase, meaning that water managers will likely need to plan for a system that is more sensitive to weather variations.
Alzheimer’s disease (AD) is a neurodegenerative disorder that is characterized by the formation of extracellular amyloid- β (A β) plaques. The underlying cause of AD is unknown, however, post-translational modifications (PTMs) of A β have been found in AD patients and are thought to play a role in protein aggregation. One such PTM is pyroglutamylation, which can occur at two sites in A β, Glu3 and Glu11. This modification of A β involves the truncation and charge-neutralization of N-terminal glutamate, causing A β to become more hy- drophobic and prone to aggregation. The molecular mech- anism by which the introduction of pyroglutamate (pE) pro- motes aggregation has not been determined. To gain a greater understanding of the role that charge neutralization and trun- cation of the N-terminus plays on A β conformational sam- pling, we used the Drude polarizable force field (FF) to per- form molecular dynamics simulations on A β pE3-42 and A β pE11-42 and comparing their properties to previous simulations of A β 1-42. The Drude polarizable FF allows for a more accurate representation of electrostatic interactions, therefore pro- viding novel insights into the role that charge plays in pro- tein dynamics. Here, we report the parametrization of pE in the Drude polarizable FF and the effect of pyroglutamyla- tion on A β. We found that A β pE3-42 and A β pE11-42 alter the permanent and induced dipoles of the peptide. Specifically, we found that A β pE3-42 and A β pE11-42 have modification- specific backbone and sidechain polarization response and perturbed solvation properties that shift the A β conforma- tional ensemble.
Differences between autistic and non-autistic individuals in perception of the temporal relationships between sights and sounds are theorized to underlie difficulties in integrating relevant sensory information. These, in turn, are thought to contribute to problems with speech perception and higher level social behaviors. However, the literature establishing this connection often involves limited sample sizes and focuses almost entirely on children. To determine whether these differences persist into adulthood, we compared 469 autistic and 373 non-autistic adults (aged 17 to 75 years). Participants completed an online version of the McGurk/MacDonald paradigm, a multisensory illusion indicative of the ability to integrate audiovisual speech stimuli. Audiovisual asynchrony was manipulated, and participants responded both to the syllable they perceived (revealing their susceptibility to the illusion) and to whether or not the audio and video were synchronized (allowing insight into temporal processing). In contrast with prior research with smaller, younger samples, we detected no evidence of impaired temporal or multisensory processing in autistic adults. Instead, we found that in both groups, multisensory integration correlated strongly with age. This contradicts prior presumptions that differences in multisensory perception persist and even increase in magnitude over the lifespan of autistic individuals. It also suggests that the compensatory role multisensory integration may play as the individual senses decline with age is intact. These findings challenge existing theories and provide an optimistic perspective on autistic development. They also underline the importance of expanding autism research to better reflect the age range of the autistic population.
Pairing assistance (PA) of health professionals between county hospitals and township health centers is one of the key components of the reform of medical alliances in China to strengthen the development of health workforce in primary health care (PHC). This study aims to examine the effect of PA on healthcare utilization for patients with chronic diseases in rural areas. Two waves of National Health Services Survey (2013 and 2018) were used. A total of 13893 and 22725 rural residents with chronic diseases were included in the 2013 and 2018 waves, respectively. Multiple logistic regressions were used to examine the associations between PA and outpatient and inpatient service utilization in PHC. Chow test was used to examine the difference between PA in two models. Among rural patients with chronic diseases, two-week outpatient visits increased from 22.69% to 27.54%, and annual hospitalization admission increased from 20.72% in 2013 to 25.44%. PA was associated with a significant decrease in outpatient visits (p<0.001) in 2018 after controlling for individual and county characteristics. Patients in PA counties were 1.45 times (95% CI 1.10-1.90) more likely to use PHC outpatient care in 2013, but the difference disappeared in 2018 (OR=0.85, 95% CI 0.71-1.01). PA did not reverse the downward trend in the share of PHC outpatient visits. PA under medical alliances in China provides a potential model for building integrated people-centered health systems for other low- and middle-income countries.
Introduction: COVID-19 pandemic led to significant reductions in influenza detection worldwide, making influenza trends challenging to monitor. The number of influenza cases decreased significantly in Japan, raising concerns about the potential risk of decreased immunity to influenza in the population. Our single-center study aimed to investigate influenza trends before and during the COVID-19 pandemic in Tokyo, Japan. Materials and Methods: This cross-sectional study included patients of all ages who visited Tokyo Shinagawa Hospital between April 1, 2018, and March 31, 2023. Influenza and COVID-19 tests were conducted using Quick Navi-Flu2 and polymerase chain reaction (PCR). We analyzed data from before and during the COVID-19 epidemic, based on patient background, hospitalization, and deaths, collected from medical records. Results: A total of 12,577 influenza tests were conducted, with approximately 100 tests consistently performed each month even in the influenza off-season. Throughout the observation period, 962 positive cases were identified. However, no cases were observed for 27 months between March 2020 and November 2022. Cases of influenza A were observed again in December 2022, and cases of influenza B were observed again in March 2023, similar to the influenza incidence reports from Tokyo. The positivity rate during the 2022–2023 winter season was lower than before the COVID-19 epidemic and decreased in elderly patients, with no hospitalizations or deaths observed. Conclusion: This single-center study provided actual trend data for influenza patients before and during COVID-19 outbreaks in Tokyo, which could offer insights into the potential impact and likelihood of influenza virus infection in Japan.
Background: Compelling evidence suggests associations between influenza infection and thromboembolism (TE) events. Risk factors related to the outcomes of severe influenza-complicated TE in intensive care unit (ICU) patients remain unknown. Methods: A retrospective cohort study was conducted, recruiting consecutive patients with thromboembolism (TE) events admitted to the intensive care unit (ICU) between December 2015 through December 2018 at our institution in Taiwan. A study cohort of patients with severe influenza (n=108) and a control group of patients with severe community-acquired pneumonia (n=192) were included. Associations between complicated TE, length of ICU stay, 90-day mortality were evaluated. Results: Thromboembolism events prevalence was significantly higher in ICU patients with severe influenza than in ICU patients with severe CAP (21.3% vs. 5.7%, respectively; p<0.05). The ratio of mechanical ventilation use, length of mechanical ventilation use, ICU stay and 90-day mortality increased significantly in ICU patients with severe influenza after developing TE compared with patients without TE (all p<0.05). Influenza infection and hypertension are the risk factors for thromboembolic events in patients with severe influenza (p< 0.05). Besides, complicated TE and severity of APACHE II score are risk factors for 90-day mortality in ICU patients with severe influenza (p< 0.05). Conclusions: ICU patients with severe influenza and complicated TE have an increased risk of extended ICU stay and 90-day mortality compared to patients with severe CAP. Risk is significantly increased in patients with higher APACHE II score. this study may help define better strategies for early recognition and prevention of severe influenza-complicated TE.
RATIONALE: In stable isotope mass spectrometry, isotope values are normalized to internationally recognized reference scales using certified reference materials and working standards. Numerous techniques exist for performing this normalization, but these methodologies need to be experimentally assessed to compare their impact on reproducibility of isotope results. METHODS: We tested normalization methods by the number of standards used, their matrix, their isotope range, and whether normalization required extrapolating beyond the isotope range. Using 8 certified reference materials and 5 working standards on a ThermoFinnigan Delta-V IRMS and Elementar VisION IRMS for nitrogen and carbon isotope composition via solid combustion with an elemental analyzer, we computed every possible isotope normalization (n=6272). Additionally, we assessed how sample matrix impacted linearity effects on both instruments. RESULTS: Normalizations composed of three or four reference materials had better performance than one-point and two-point methods, especially when the normalization was matrix-mixed or extrapolated, and normalizations with an isotope range greater than 15‰ were more accurate under these conditions. Normalizations that were matrix-matched and were not extrapolated exhibited the highest accuracy. Linearity effects were found to exceed instrument precision by two orders of magnitude irrespective of sample matrix and were not predicted by reference gas diagnostics. CONCLUSIONS: To maximize interlaboratory comparability of isotope results, operators of EAIRMS systems should use at least 3 calibration standards to construct their normalizations, select standards with a large isotope range to avoid extrapolation, and match the matrix of their standards to their samples to the best extent possible.
Rationale: Diaryliodonium salts are useful electrophilic reagents in organic chemistry, finding extensive applications in arylations and photo-induced polymerizations. However, the comprehensive mechanistic investigations, particularly concerning the mass spectrometric behaviors of diaryliodonium salts, are relatively scarce in the literatures. Methods: Diaryliodonium salts could be readily ionized in ESI-MS to give [Ar 1-I +-Ar 2], and the high-resolution ESI-MS/MS experiments were conducted to investigate their gas-phase chemical reactions. Results: Investigations on ESI-MS/MS of [Ar 1-I +-Ar 2] revealed two major fragmentation patterns: 1) Reductive elimination resulting the diaryl coupling product ion [Ar 1-Ar 2] +• by the loss of I. 2) Generating aryl cations [Ar 1] + or [Ar 2] + through cleavage of the C–I bonds. We unrevealed that the introduction of NO 2 into Ar 2 of [Ar 1-I +-Ar 2] could lead to an unexpected fragmentation ion [Ar 1O] + in MS/MS, arising from an O-atom transfer process from NO 2 to Ar 1. Particularly, when NO 2 was ortho-positioned to the iodine in Ar 2, the [Ar 1O] + sometimes exhibited dominant behavior. Conclusions: Comprehensive ESI-MS/MS studies and theoretical calculations provided strong support for the O-atom transfer mechanistic pathway: [Ar 1-I +-( o-NO 2-Ar 2)] initially underwent a Smiles rearrangement to the intermediate [Ar 1-O-( o-NO-Ar 2I)] +, which subsequently dissociated to [Ar 1O] + or [ o-NO-Ar 2I] +•. Herein, we proposed an unexpected ” ortho-effect” in the gas-phase fragmentation reaction of [Ar 1-I +-( o-NO 2-Ar 2)], in which the crucial determinant factor for the aryl migration was identified as the Smiles rearrangement reaction.
RATIONALE: Urine contains free and conjugated steroids. Total and free steroids were comprehensively quantified; UPLC-MS/MS based on Li adduction allowed for detecting thirteen 3-OH-containing steroids, two of which were detected in human urine for the first time. METHODS: Free urinary steroids were isolated by solid-phase extraction (SPE) with 80% acetonitrile. The total steroids were prepared by enzymatic treatment of urine with a cocktail of sulfatase and glucronidase, protein precipitation, and separation with the above SPE. The free and total steroids were separately analyzed by UPLC-MS/MS with and without introduction of Li + solution. The steroids were quantified by two standard curves created using product ion transitions derived from MH + and [M+Li] +. RESULTS: Two groups of human urine, male and female urine, were analyzed. The absolute amount of each steroid was determined based on creatinine levels. The differences between the male and female groups are clearly attributable to sex steroids. 7-OH P5 and 7-OH DHEA were, for the first time, quantified in the total steroids of female urine, and the latter was identified in both female and male urine. CONCLUSIONS: By combining UPLC-MS/MS based on lithium ion incorporation with conventional UPLC-MS/MS, a total of 29 steroids were identified in human urine containing two newly found steroids.
Vascular smooth muscle cell (vSMC) dysfunction is a critical contributor to cardiovascular diseases, including atherosclerosis, restenosis, and vein graft failure. Recent advances have unveiled a fascinating breadth of non-coding RNAs (ncRNAs) that play a pivotal role in regulating vSMC function. This review aims to provide an in-depth analysis of the mechanisms underlying vSMC dysfunction and the therapeutic potential of various ncRNAs in mitigating this dysfunction, either preventing or reversing it. We explore the intricate interplay of microRNAs, long-non-coding RNAs and circular RNAs, shedding light on their roles in regulating key signalling pathways associated with vSMC dysfunction. Moreover, we discuss the prospects and challenges associated with developing ncRNA based therapies for this prevalent cardiovascular pathology.