bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety, tolerability, pharmacodynamics and pharmacokinetics of the soluble guanylyl cyclase activator BI 685509 in patients with diabetic kidney disease: A randomized trial
Authors: Cherney David Z. I. , de Zeeuw Dick , Heerspink Hiddo J. L. , Cardona Jose , Desch Marc , Wenz Arne , Schulze Friedrich , Nangaku Masaomi
Published: May 2023

Aims

Albuminuria is associated with abnormalities in the nitric oxide (NO)–soluble guanylyl cyclase (sGC)–cyclic guanosine monophosphate pathway. We assessed safety and efficacy of the NO‐independent sGC activator BI 685509 in patients with diabetic kidney disease and albuminuria.

Materials and methods

In this Phase Ib trial (NCT03165227), we randomized patients with type 1 or 2 diabetes, estimated glomerular filtration rate (eGFR) 20–75 mL/min/1.73 m2 and urinary albumin:creatinine ratio (UACR) 200–3500 mg/g to oral BI 685509 (1 mg three times daily, n = 20; 3 mg once daily, n = 19; 3 mg three times daily, n = 20, after final titration) or placebo (n = 15) for 28 days. Changes from baseline in UACR in first morning void (UACRFMV) and 10‐hour (UACR10h) urine (3 mg once daily/three times daily only) were assessed.

Results

Baseline median eGFR and UACR were 47.0 mL/min/1.73 m2 and 641.5 mg/g, respectively. Twelve patients had drug‐related adverse events (AEs; 16.2%: BI 685509, n = 9; placebo, n = 3), most frequently hypotension (4.1%: BI 685509, n = 2; placebo, n = 1) and diarrhoea (2.7%: BI 685509, n = 2; placebo, n = 0). Four patients experienced AEs leading to study discontinuation (5.4%: BI 685509, n = 3; placebo, n = 1). Placebo‐corrected mean UACRFMV decreased from baseline in the 3‐mg once‐daily (28.8%, P = 0.23) and three‐times‐daily groups (10.2%, P = 0.71) and increased in the 1‐mg three‐times‐daily group (6.6%, P = 0.82); changes were not significant. UACR10h decreased by 35.3% (3 mg once daily, P = 0.34) and 56.7% (3 mg three times daily, P = 0.09); ≥50.0% of patients (UACR10h 3 mg once daily/three times daily) responded (≥20% UACR decrease from baseline).

Conclusions

BI 685509 was generally well tolerated. Effects on UACR lowering merit further investigation.
How valuable is FinTech adoption for traditional banks?
Authors: Bian Wenlong , Wang Shihui , Xie Xuanli
Published: May 2023

This study examines the effect of FinTech adoption on traditional banks. We employ machine learning and textual analysis to count the number of mentions of FinTech‐related terms in annual reports, and collect the number of FinTech‐related patent applications. Based on a sample of 181 Chinese commercial banks, the results indicate that FinTech adoption has a positive and significant effect on bank performance. The ‘FinTech adoption effect’ appear to be heterogeneous among technology categories and is more pronounced in banks with more tech managers. Last, we examine the impacts of FinTech adoption on bank risk, business transformation and banks' market share.
An investigation of artificial neural network structure and its effects on the estimation of the low‐cycle fatigue parameters of various steels
Authors: Soyer Mehmet Alperen , Tüzün Nail , Karakaş Özler , Berto Filippo
Published: May 2023

Artificial neural networks (ANNs) are a widely used machine learning approach for estimating low‐cycle fatigue parameters. ANN structure has its parameters such as hidden layers, hidden neurons, activation functions, training functions, and so forth, and these parameters have a significant influence over the results. Three hidden layer combinations, the hidden neurons ranging from 1 to 25, and different activation functions like hyperbolic tangent sigmoid (tansig), logistic sigmoid (logsig), and linear (purelin) were used, and their effects on the low‐cycle fatigue parameter estimation were investigated to determine optimal ANN structure. Based on the results, suggestions regarding ANN structure for the estimation of the low‐cycle fatigue parameters and transition fatigue life were presented. For the output layer and hidden layers, the most suitable activation function was tansig. The optimal hidden neuron range has been found between 4 and 9. The neural network structure with one hidden layer was determined to be most suitable in terms of less knowledge, structural complexity, and computational time and power.
A global satellite observation of phytoplankton taxonomic groups over the past two decades
Authors: Li Zhenghao , Sun Deyong , Wang Shengqiang , Huan Yu , Zhang Hailong , Liu Jianqiang , He Yijun
Published: May 2023

Marine phytoplankton fuel the oceanic biotic chain, determine the carbon sequestration levels, and are crucial for the global carbon cycle and climate change. In the present study, we show a near‐two‐decadal (2002–2022) spatiotemporal distribution of global phytoplankton abundance, proxy as dominant phytoplankton taxonomic groups (PTGs), with a newly developed remote sensing model. Globally, six chief PTGs, namely chlorophytes (~26%), diatoms (~24%), haptophytes (~15%), cryptophytes (~10%), cyanobacteria (~8%), and dinoflagellates (~3%), explain most of the variation (~86%) in phytoplankton assemblages. Spatially, diatoms generally dominate high latitudes, marginal seas, and coastal upwelling zones, whereas chlorophytes and haptophytes control the open oceans. Satellite observations reveal a gentle multi‐annual trend of the PTGs in the major oceans, indicative of roughly “unchanged” conditions on the total biomass or compositions of the phytoplankton community. Jointly, “changed” status applies to a short‐term (seasonal) timescale: (1) Fluctuations of PTGs exhibit different amplitudes among different subregions, together with a general rule‐more intense vibration in the Northern Hemisphere and polar oceans than other zones; (2) diatoms and haptophytes vary more dramatically than other PTGs in a global‐scale scope. These findings provide a clear picture of the global phytoplankton community composition and can improve our understanding of their state and further analysis of marine biological processes.
Person‐centred sexual and reproductive health: A call for standardized measurement
Authors: Afulani Patience A. , Nakphong Michelle K. , Sudhinaraset May
Published: May 2023

Person‐centred sexual and reproductive health (PCSRH) care refers to care that is respectful of and responsive to people's preferences, needs, and values, and which empowers them to take charge of their own sexual and reproductive health (SRH). It is an important indicator of SRH rights and quality of care. Despite the recognition of the importance of PCSRH, there is a gap in standardized measurement in some SRH services, as well as a lack of guidance on how similar person‐centred care measures could be applied across the SRH continuum. Drawing on validated scales for measuring person‐centred family planning, abortion, prenatal and intrapartum care, we propose a set of items that could be validated in future studies to measure PCSRH in a standardized way. A standardized approach to measurement will help highlight gaps across services and facilitate efforts to improve person‐centred care across the SRH continuum.

Patient or Public Contribution

This viewpoint is based on a review of validated scales that were developed through expert reviews and cognitive interviews with services users and providers across the different SRH services. They provided feedback on the relevance, clarity, and comprehensiveness of the items in each scale.
Encapsulated papillary carcinoma of the breast: does it have a native basement membrane?
Authors: Ghannam Suzan F , Rutland Catrin S , Allegrucci Cinzia , Mongan Nigel P , Rakha Emad
Published: May 2023

Background

Encapsulated papillary carcinoma (EPC) is surrounded by a thick fibrous capsule‐like structure, which is interpreted as a thickened basement membrane (BM). This study aimed to describe the geometric characteristics of the EPC capsule and to refine whether it is an expansion of the BM or a stromal reactive process.

Material and Methods

In all, 100 cases were divided into four groups: EPC, ductal carcinoma in situ (DCIS), normal breast tissue and invasive tumours, with an additional encapsulated papillary thyroid carcinoma (EPTC) control group. Representative slides from each case were stained with picrosirius red (PSR) stain and examined using polarised microscopy. Images were analysed using ImageJ, CT‐FIRE, and Curve align image analysis programmes.

Results

Compared to the normal and DCIS BM, the EPC group showed a significant increase of collagen fibre width, straightness, and density, and a decrease of fibre length. The EPC capsule showed less alignment of fibres with a more perpendicular arrangement, and it was enriched with disorganised collagen type I (stromal collagen) fibres. Compared to other groups, the EPC capsule showed significant variation in the thickness, evenness, distribution of collagen fibres, and significant intracapsular heterogeneity. Compared to BM‐like material in the invasive group, the EPC capsule showed a higher density of collagen fibres with longer, straighter, and more aligned fibres, but there was no difference in the distribution of both collagen types I and III. Conversely, compared to EPTC, there were no differences between both EPC and EPTC capsules except that the fibres in the EPC capsule were straighter. Although differences between normal ducts and lobules and DCIS BM collagen fibre density, straightness, orientation, and alignment were detected, both were significantly different from EPC capsule.

Conclusion

This study provided evidence that the EPC capsule is a reactive process rather than a thickened native BM characteristic of normal and in situ lesions, which provides further evidence that EPC is an indolent invasive carcinoma based on capsule characteristics.
The limits of using grievance procedures to combat workplace discrimination
Authors: Narayan Ayushi
Published: May 2023

I examine the move from phone to online Equal Employment Opportunity (EEO) reporting at the United States Postal Service (USPS) to identify the causal impact of grievance procedure use. This shift led to a large increase in sex–based complaints at the USPS in areas with greater access to broadband. However, I observe no commensurate change in sex gaps related to turnover, hiring, and promotions. My results suggest that a 10% increase in sex–based complaints changes the female share in separations or hires by less than 1%. Increased investment in grievance procedures appears unlikely to significantly influence discrimination outcomes.
Spillover analysis across FinTech, ESG, and renewable energy indices before and during the Russia–Ukraine war: International evidence
Authors: El Khoury Rim , Nasrallah Nohade , Hussainey Khaled , Assaf Rima
Published: May 2023

This study is epicentral to analyze the impact of the Russia–Ukraine war on the financial markets, specifically focusing on the connectedness and spillover dynamics of FinTech, Environmental, Social, and Governance (ESG), renewable energy, gold, and Morgan Stanley Capital International (MSCI) indices in developed and emerging countries. Data are collected from Thomson Reuters, ranging from May 8, 2020, to May 11, 2022, and a time‐varying parameter vector autoregression (TVP‐VAR) and the dynamic conditional correlation (DCC) generalized autoregressive conditional heteroskedasticity (GARCH) t‐Copula (DCC‐GARCH t‐Copula) are used to analyze the data. The results show that FinTech, ESG, and MSCI are net transmitters in developed countries, whereas gold and renewable energy are net receivers pre‐ and during war periods. ESG and MSCI are net transmitters in emerging countries, while FinTech, renewable energy, and gold become net receivers in both periods. The hedging ratio sheds light on the costs and weights of efficient pair investments that might change in the context of each region and under the combined scenario. The study has important implications for merchant bankers, policymakers, investors, hedgers, and risk managers.
Metabolic profiles in plasma of patients with herpes labialis based on GC–MS
Authors: Luo Mengxian , Guan Jin‐Tao , Yu Xiu , Ding Yunfei , Mei Xian‐Xian , Pan Xiaoping , Fan Yong‐Sheng , Xu Zheng‐Hao
Published: May 2023

Objective

This study aims to compare the plasma metabolic profiles of patients with herpes labialis with healthy controls and identify the biomarkers of herpes labialis.

Subjects and Methods

We collected 18 patients with herpes labialis and 20 healthy individuals. Plasma samples from both groups were analyzed using gas chromatography–mass spectrometry (GC–MS).

Results

According to the principal component analysis (PCA) and partial least squares discriminant analysis (PLS‐DA), we found that metabolic profiles had changed in patients with herpes labialis compared to the controls. By further selecting the different metabolites according to the variable importance in the projection (VIP) and p valve of t‐tests, we found that acetic acid, pyroglutamic acid, alanine, ethanedioic acid, cyclohexaneacetic acid, pyruvic acid, d‐mannose, phosphoric acid, l‐amphetamine, and citric acid were decreased in patients with herpes labialis, while sedoheptulose and ethylamine were increased. Pathway analysis showed that herpes labialis may affect the amino acid and energy metabolism.

Conclusions

Our findings may contribute to elucidating the metabolic basis of herpes labialis and provide a new perspective for further research on the “Shang‐Huo” state in traditional Chinese medicine (TCM).
Description of a novel method for detection of sleep‐disordered breathing in brachycephalic dogs
Authors: Niinikoski Iida , Himanen Sari‐Leena , Tenhunen Mirja , Lilja‐Maula Liisa , Rajamäki Minna M.
Published: May 2023

Background

Sleep‐disordered breathing (SDB), defined as any difficulty in breathing during sleep, occurs in brachycephalic dogs. Diagnostic methods for SDB in dogs require extensive equipment and laboratory assessment.

Objectives

To evaluate the usability of a portable neckband system for detection of SDB in dogs. We hypothesized that the neckband is a feasible method for evaluation of SDB and that brachycephaly predisposes to SDB.

Animals

Twenty‐four prospectively recruited client‐owned dogs: 12 brachycephalic dogs and 12 control dogs of mesocephalic or dolicocephalic breeds.

Methods

Prospective observational cross‐sectional study with convenience sampling. Recording was done over 1 night at each dog's home. The primary outcome measure was the obstructive Respiratory Event Index (OREI), which summarized the rate of obstructive SDB events per hour. Additionally, usability, duration of recording, and snore percentage were documented.

Results

Brachycephalic dogs had a significantly higher OREI value (Hodges‐Lehmann estimator for median difference = 3.5, 95% confidence interval [CI] 2.2‐6.8; P < .001) and snore percentage (Hodges‐Lehmann estimator = 34.2, 95% CI 13.6‐60.8; P < .001) than controls. A strong positive correlation between OREI and snore percentage was detected in all dogs (rs = .79, P < .001). The neckband system was easy to use.

Conclusions and Clinical Importance

Brachycephaly is associated with SDB. The neckband system is a feasible way of characterizing SDB in dogs.
Daytime stomatal regulation in mature temperate trees prioritizes stem rehydration at night
Authors: Peters Richard L. , Steppe Kathy , Pappas Christoforos , Zweifel Roman , Babst Flurin , Dietrich Lars , von Arx Georg , Poyatos Rafael , Fonti Marina , Fonti Patrick , Grossiord Charlotte , Gharun Mana , Buchmann Nina , Steger David N. , Kahmen Ansgar
Published: May 2023

Trees remain sufficiently hydrated during drought by closing stomata and reducing canopy conductance (Gc) in response to variations in atmospheric water demand and soil water availability. Thresholds that control the reduction of Gc are proposed to optimize hydraulic safety against carbon assimilation efficiency. However, the link between Gc and the ability of stem tissues to rehydrate at night remains unclear.

We investigated whether species‐specific Gc responses aim to prevent branch embolisms, or enable night‐time stem rehydration, which is critical for turgor‐dependent growth. For this, we used a unique combination of concurrent dendrometer, sap flow and leaf water potential measurements and collected branch‐vulnerability curves of six common European tree species.

Species‐specific Gc reduction was weakly related to the water potentials at which 50% of branch xylem conductivity is lost (P50). Instead, we found a stronger relationship with stem rehydration. Species with a stronger Gc control were less effective at refilling stem‐water storage as the soil dries, which appeared related to their xylem architecture.

Our findings highlight the importance of stem rehydration for water‐use regulation in mature trees, which likely relates to the maintenance of adequate stem turgor. We thus conclude that stem rehydration must complement the widely accepted safety–efficiency stomatal control paradigm.
Could local foods achieve recommended calcium intakes for nutritionally vulnerable populations in Uganda, Guatemala, and Bangladesh?
Authors: Knight Frances , Rana Ziaul H. , Cormick Gabriela , Belizan José , Gomes Filomena , Bourassa Megan W. , Dickin Katherine L. , Weaver Connie M. , Ferguson Elaine L.
Published: May 2023

Globally, dietary intake of calcium is often insufficient, and it is unclear if adequacy could be achieved by promoting calcium‐rich local foods. This study used linear programming and household consumption data from Uganda, Bangladesh, and Guatemala to assess whether local foods could meet calcium population reference intakes (Ca PRIs). The most promising food‐based approaches to promote dietary calcium adequacy were identified for 12‐ to 23‐month‐old breastfed children, 4‐ to 6‐year‐old children, 10‐ to 14‐year‐old girls, and nonpregnant and nonbreastfeeding (NPNB) women of reproductive age living in two regions of each country. Calcium‐optimized diets achieved 75–253% of the Ca PRI, depending on the population, and were <100% for 4‐ to 6‐year‐olds in one region of each country and 10‐ to 14‐year‐old girls in Sylhet, Bangladesh. The best food sources of calcium were green leafy vegetables and milk, across geographic locations, and species of small fish, nixtamalized (lime‐treated) maize products, sesame seeds, and bean varieties, where consumed. Food‐based recommendations (FBRs) achieving the minimum calcium threshold were identified for 12‐ to 23‐month‐olds and NPNB women across geographic locations, and for 4‐ to 6‐year‐olds and 10‐to 14‐year‐old girls in Uganda. However, for 4‐ to 6‐year‐olds and 10‐ to 14‐year‐old girls in Bangladesh and Guatemala, calcium‐adequate FBRs could not be identified, indicating a need for alternative calcium sources or increased access to and consumption of local calcium‐rich foods.
The craft of translation: documentary practices within immigration advocacy in the United States
Authors: Coutin Susan Bibler , Fortin Véronique
Published: May 2023

This article builds on anthropological research on bureaucratic inscription as a power‐laden process to explore the craft of document translation in contexts of immigration legal advocacy. In a legal climate characterized by suspicion and resource scarcity, immigrants who seek to regularize their status in the United States face steep evidentiary challenges, including the requirement that all documentation, including records from their countries of origin, letters of support from friends and family, and their own affidavits, must be translated into English. Approaching immigration document translation ethnographically and drawing on multi‐year fieldwork in a nonprofit providing legal services to low‐income, Spanish‐speaking immigrants, this article focuses on translation as neither straightforward and mechanical nor as impossibly complex but rather as a craft that involves exercising discretion. Practicing this craft with care is one way to counter the otherwise alienating and state‐centric nature of bureaucratic inscription.
Correction of China's income inequality for missing top incomes
Authors: Wan Haiyuan , Yu Yangcheng
Published: May 2023

After accounting for top incomes missing from the Chinese Household Income Project, this paper examines the income inequality trend in China during the 21st century. Our analysis, which involves fitting the upper tail of the income distribution to a power‐law model, reveals that the authoritative income survey data miss 0.68% of the population and 6.19% of aggregate income in 2018. Despite the most recent survey data providing better coverage of top incomes, our correction is still crucial. The raw survey data indicate a consistently increasing Gini coefficient between 2002 and 2018, but the corrected index starts to decline from 2013. Meanwhile, the revised top 1% income share increases from 7.01% in 2002 to 7.89% in 2013 and then slightly decreases to 7.64% in 2018, while the revised top 10% income share stabilises at around 33% throughout the period. Notably, China's revised top 10% and top 50% income shares in 2018 are close to those of the United Kingdom but are considerably lower than those of the United States.
Challenges in water and sanitation services: Do natural disasters make matters worse?
Authors: Paudel Jayash
Published: May 2023

This article exploits a plausibly exogenous variation in peak ground acceleration to evaluate the impact of the 2015 earthquake on water and sanitation services among affected households in Nepal. Estimates from a difference‐in‐differences research design show that the severity of the earthquake is associated with a 9.4 percentage point decline in the likelihood of washing hands, a 6.63 percentage point decline in the likelihood of using water filters and an 18.16 percentage point decline in the likelihood of using flush to a piped sewer system. These negative effects of seismic shocks on binary indicators of water treatment and toilet services continue to persist even in earthquake‐affected districts where aid for water, sanitation, and hygiene (WASH) services was allocated for disbursement. While prospects of leakage in aid distribution across different levels of governance cannot be empirically tested, findings indicate that effective implementation of WASH‐related aid can partially mitigate disaster‐induced adverse outcomes related to water treatment and toilet services.
A simple soil organic carbon level metric beyond the organic carbon‐to‐clay ratio
Authors: Poeplau Christopher , Don Axel
Published: May 2023

Soil is a precious and non‐renewable resource that is under increasing pressure and the development of indicators to monitor its state is pivotal. Soil organic carbon (SOC) is important for key physical, chemical and biological soil properties and thus a central indicator of soil quality and soil health. The content of SOC is driven by many abiotic factors, such as texture and climate, and is therefore strongly site‐specific, which complicates, for example, the search for appropriate threshold values to differentiate healthy from less healthy soils. The SOC:clay ratio has been introduced as a normalized SOC level metric to indicate soils' structural condition, with classes ranging from degraded (<1:13) to very good (>1:8). This study applied the ratio to 2958 topsoils (0–30 cm) in the German Agricultural Soil Inventory and showed that it is not a suitable SOC level metric since strongly biased, misleading and partly insensitive to SOC changes. The proportion of soils with SOC levels classified as degraded increased exponentially with clay content, indicating the indicator's overly strong clay dependence. Thus, 94% of all Chernozems, which are known to have elevated SOC contents and a favourable soil structure, were found to have either degraded (61%) or moderate (33%) normalized SOC levels. The ratio between actual and expected SOC (SOC:SOCexp) is proposed as an easy‐to‐use alternative where expected SOC is derived from a regression between SOC and clay content. This ratio allows a simple but unbiased estimate of the clay‐normalized SOC level. The quartiles of this ratio were used to derive threshold values to divide the dataset into the classes degraded, moderate, good and very good. These classes were clearly linked to bulk volume (inverse of bulk density) as an important structural parameter, which was not the case for classes based on the SOC:clay ratio. Therefore, SOC:SOCexp and its temporal dynamic are proposed for limited areas such as regions, states or pedoclimatic zones, for example, in a soil health monitoring context; further testing is, however, recommended.
High CO2 facilitates fatty acid biosynthesis and mitigates cellular oxidative stress caused by CAC2 dysfunction in Arabidopsis
Authors: Xi Yue , Cai Jiajia , Li Ganting , Huang Haijian , Peng Xinxiang , Zhu Guohui
Published: May 2023

Increasing concentration of CO2 has significant impacts on many biological processes in plants, and its impact is closely associated with changes in the ratio of photosynthesis to photorespiration. Studies have reported that high CO2 can promote carbon fixing and alleviate plant oxidative damage in response to environmental stresses. However, the effect of high CO2 on fatty acid (FA) metabolism and cellular redox balance in FA‐deficient plants is rarely reported. In this study, we identified a high‐CO2‐requiring mutant cac2 through forward genetic screening. CAC2 encodes biotin carboxylase, which is one of the subunits of plastid acetyl‐CoA carboxylase and participates in de novo FA biosynthesis. Null mutation of CAC2 is embryonic lethal. A point mutation of CAC2 in cac2 mutants produces severe defects in chloroplast development, plant growth and photosynthetic performance. These morphological and physiological defects were largely absent under high CO2 conditions. Metabolite analyses showed that FA contents in cac2‐1 leaves were decreased, while photorespiratory metabolites, such as glycine and glycolate, did not significantly change. Meanwhile, cac2 exhibited higher reactive oxygen species (ROS) levels and mRNA expression of stress‐responsive genes than the wild‐type, indicating that cac2 plants may suffer oxidative stress under ambient CO2 conditions. Elevated CO2 significantly increased FA contents, especially C18:3‐FA, and reduced ROS accumulation in cac2‐1 leaves. We propose that stress mitigation by high CO2 in cac2 could be due to increased FA levels by promoting carbon assimilation, and the prevention of over‐reduction due to decreased photorespiration.
Repeat patient testing‐quality control with canine samples shows promise as an alternative to commercial quality control material for a network of four Sysmex XT‐2000iV hematology analyzers
Authors: Daly Susan , Graham Peter A. , Freeman Kathleen P.
Published: May 2023

Background

Repeat patient testing‐quality control (RPT‐QC) uses retained patient samples as an alternative to commercial quality control material (QCM). We elected to calculate and validate RPT‐QC limits for red blood cell count (RBC), hemoglobin (HBG), hematocrit (HCT), and white blood cell count (WBC).

Objectives

(1) To validate RPT‐QC across a network of four harmonized Sysmex XT‐2000iV hematology analyzers and determine the total error that can be controlled with RPT‐QC. (2) To generate quality control (QC) limits using the standard deviation (SD) of the duplicate measurement differences and determine a suitable simple QC rule with a probability of error detection >0.85 and probability of false rejection <0.05. (3) Monitor RPT‐QC using sigma metrics as a performance indicator and (4) to challenge RPT‐QC to ensure acceptable sensitivity.

Methods

Fresh adult canine EDTA samples with results within reference intervals were selected and run again on days 2, 3, and 4. QC limits were generated from the SD of the duplicate measurement differences. The QC limits were challenged using interventions designed to promote unstable system performance. The total error detectable by RPT‐QC was determined using EZRULES 3 software.

Results

In all, 20‐40 data points were needed for RPT‐QC calculations and validated using 20 additional data points. The calculated limits differed among the network of analyzers. The total error that could be controlled was the same or better than that of the manufacturer's commercially available quality control material using the same analyzer for all measurands except hematocrit, which required a higher total error goal than that proposed by ASVCP guidelines to achieve an acceptable probability of error detection. The challenges designed to mimic unstable system performance were successfully detected as out‐of‐control QC.

Conclusions

The challenges for RPT‐QC resulted in acceptable detection of potential unstable system performance. This initial study demonstrates that RPT‐QC limits differ among the network of Sysmex XT‐2000iV analyzers, indicating a requirement to customize for the individual analyzer and laboratory conditions. RPT‐QC could achieve ASVCP total allowable error goals for RBC, HGB, and WBC, but not for HCT. Sigma metrics were consistently >5.5 for RBC, HGB, and WBC, but not for HCT.
Design a Crime Detection System based Fog Computing and IoT
Authors: Waheed Safa Riyadh , Sakran Ammar AbdRoba , Mohd Rahim Mohd Shafry , Mohd Suaib Norhaida , H Najjar Fallah , A Kadhim Karrar , Salim Ali Aqeel , Adnan Myasar Mundher
Published: May 2023

The Internet of Things (IoT) is a cutting-edge innovation that facilitates the cost-effective development of smart system architectures. Although current regulations necessitate installing an analog fire alarm system, such a system lacks the intelligence to instantly notify the appropriate parties in a timely fashion. In addition, since people are not always present, an analog fire alarm will not be able to prevent immediate danger or damage in the event of a fire. Therefore, the incident must be reported as soon as possible to the appropriate party in order to lessen the impact of a fire. In this study, we suggest a smart fire-alarm system made of a fire sensor and a sound sensor that can both detect fire and noise as well as the status of the analog fire alarm system to ascertain whether the analog fire alarm system is operational. We first tested our proposed smart fire alarm system to determine its effectiveness before putting it into use. From there, we ran experiments to determine how well it worked. The outcomes show that the system is trustworthy in a range of scenarios.
The Influence of Athletic Identity, Passion, and Perceptions of Severity of Concussions on Athletes’ Willingness to Report Concussion Symptoms
Authors: Martin Eric M. , Byrd Megan , Amador Adriana , Ridenhour Emma , Charalambous Carolena
Published: May 2023

Context: The influence of several psychological characteristics on the willingness of athletes to report concussion behaviors has not been well explored. Therefore, the purpose of this study was to understand how athletic identity and sport passion predicted participants’ willingness to report symptoms above what was explained by athlete demographics, concussion knowledge, and perceived seriousness of concussions. Design: The study was cross-sectional. Methods: Three-hundred and twenty-two male and female high school and club sport athletes completed survey measures of concussion knowledge, athletic identity, harmonious and obsessive passion, and degree to which athletes indicated they would report concussions and concussion symptoms. Results: Athletes scored moderately high on their knowledge of symptoms and other concussion information (mean = 16.21; ± = 2.88) and above the midpoint on their attitudes and behaviors toward reporting concussion symptoms (mean = 3.64; ± = 0.70). There were no differences between gender, t(299) = −.78, P = .44, and previous concussion education, t(296) = 1.93, P = .06, related to concussion knowledge. Results of a hierarchical regression indicated that after entering athlete demographics, concussion knowledge, and perceived seriousness of concussions, of the 3 psychological variables in the final stage of the model, only obsessive passion was a significant predictor of athlete’s attitudes to report a concussion. Conclusions: Perceived seriousness of concussion, perceived threat to long-term health, and obsessive passion were the strongest predictors of athlete’s willingness to report concussions. Athletes who did not believe concussions posed a threat to their current or future health, and those that held an obsessive passion for sport were most at risk for not reporting concussions. Future research should continue to investigate the relationship between reporting behaviors and psychological factors.
Use of race in clinical algorithms
Authors: Basu Anirban
Published: May 2023

To answer whether patients’ race belongs in clinical prediction algorithms, two types of prediction models are considered: (i) diagnostic, which describes a patient’s clinical characteristics, and (ii) prognostic, which forecasts a clinical risk or treatment effect that a patient is likely to experience in the future. The ex ante equality of opportunity framework is used, where specific health outcomes, which are prediction targets, evolve dynamically due to the effects of legacy levels of outcomes, circumstances, and current individual efforts. In practical settings, this study shows that failure to include race corrections will propagate systemic inequities and discrimination in any diagnostic model and specific prognostic models that inform decisions by invoking an ex ante compensation principle. In contrast, including race in prognostic models that inform resource allocations following an ex ante reward principle can compromise the equality of opportunities for patients from different races. Simulation results demonstrate these arguments.
Nitric oxide synthase and reduced arterial tone contribute to arteriovenous malformation
Authors: Huang Lawrence , Cheng Feng , Zhang Xuetao , Zielonka Jacek , Nystoriak Matthew A. , Xiang Weiwei , Raygor Kunal , Wang Shaoxun , Lakshmanan Aditya , Jiang Weiya , Yuan Sai , Hou Kevin S. , Zhang Jiayi , Wang Xitao , Syed Arsalan U. , Juric Matea , Takahashi Takamune , Navedo Manuel F. , Wang Rong A.
Published: May 2023

Mechanisms underlying arteriovenous malformations (AVMs) are poorly understood. Using mice with endothelial cell (EC) expression of constitutively active Notch4 (Notch4*
EC
), we show decreased arteriolar tone in vivo during brain AVM initiation. Reduced vascular tone is a primary effect of Notch4*
EC
, as isolated pial arteries from asymptomatic mice exhibited reduced pressure-induced arterial tone ex vivo. The nitric oxide (NO) synthase (NOS) inhibitor NG-nitro-
l
-arginine (L-NNA) corrected vascular tone defects in both assays. L-NNA treatment or endothelial NOS (
eNOS
) gene deletion, either globally or specifically in ECs, attenuated AVM initiation, assessed by decreased AVM diameter and delayed time to moribund. Administering nitroxide antioxidant 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl also attenuated AVM initiation. Increased NOS-dependent production of hydrogen peroxide, but not NO, superoxide, or peroxynitrite was detected in isolated Notch4*
EC
brain vessels during AVM initiation. Our data suggest that eNOS is involved in Notch4*
EC
-mediated AVM formation by up-regulating hydrogen peroxide and reducing vascular tone, thereby permitting AVM initiation and progression.
A noncommutative combinatorial protein logic circuit controls cell orientation in nanoenvironments
Authors: Chen Jiaxing , Vishweshwaraiah Yashavantha L. , Mailman Richard B. , Tabdanov Erdem D. , Dokholyan Nikolay V.
Published: May 2023

Single-protein–based devices that integrate signal sensing with logical operations to generate functional outputs offer exceptional promise for monitoring and modulating biological systems. Engineering such intelligent nanoscale computing agents is challenging, as it requires the integration of sensor domains into a functional protein via intricate allosteric networks. We incorporate a rapamycin-sensitive sensor (uniRapR) and a blue light-responsive LOV2 domain into human Src kinase, creating a protein device that functions as a noncommutative combinatorial logic circuit. In our design, rapamycin activates Src kinase, causing protein localization to focal adhesions, whereas blue light exerts the reverse effect that inactivates Src translocation. Focal adhesion maturation induced by Src activation reduces cell migration dynamics and shifts cell orientation to align along collagen nanolane fibers. Using this protein device, we reversibly control cell orientation by applying the appropriate input signals, a framework that may be useful in tissue engineering and regenerative medicine.
LIKE EARLY STARVATION 1 and EARLY STARVATION 1 promote and stabilize amylopectin phase transition in starch biosynthesis
Authors: Liu Chun , Pfister Barbara , Osman Rayan , Ritter Maximilian , Heutinck Arvid , Sharma Mayank , Eicke Simona , Fischer-Stettler Michaela , Seung David , Bompard Coralie , Abt Melanie R. , Zeeman Samuel C.
Published: May 2023

Starch, the most abundant carbohydrate reserve in plants, primarily consists of the branched glucan amylopectin, which forms semi-crystalline granules. Phase transition from a soluble to an insoluble form depends on amylopectin architecture, requiring a compatible distribution of glucan chain lengths and a branch-point distribution. Here, we show that two starch-bound proteins, LIKE EARLY STARVATION 1 (LESV) and EARLY STARVATION 1 (ESV1), which have unusual carbohydrate-binding surfaces, promote the phase transition of amylopectin-like glucans, both in a heterologous yeast system expressing the starch biosynthetic machinery and in
Arabidopsis
plants. We propose a model wherein LESV serves as a nucleating role, with its carbohydrate-binding surfaces helping align glucan double helices to promote their phase transition into semi-crystalline lamellae, which are then stabilized by ESV1. Because both proteins are widely conserved, we suggest that protein-facilitated glucan crystallization may be a general and previously unrecognized feature of starch biosynthesis.
Peak-ring magnetism: Rock and mineral magnetic properties of the Chicxulub impact crater
Authors: Mendes Bruno Daniel Leite , Kontny Agnes , Poelchau Michael , Fischer Lennart A. , Gaus Ksenia , Dudzisz Katarzyna , Kuipers Bonny W.M. , Dekkers Mark J.
Published: May 2023

The Chicxulub impact event at ca. 66 Ma left in its wake the only complex crater on Earth with a preserved peak ring, characterized by a well-developed magnetic anomaly low. To date, little is known about its magnetic properties. The joint Integrated Ocean Drilling Program (IODP) and International Continental Scientific Drilling Program (ICDP) Expedition 364 drill core M0077A revealed that the peak ring consists of uplifted and strongly deformed granitoid basement rocks overlain by a 130-m-thick impact melt and suevite layer. Pre- and postimpact hydrothermal systems affected this basement with maximum temperatures up to 450 °C. We used microscopy, mineral chemistry, temperature-dependent magnetic susceptibility, and hysteresis properties to characterize the magnetic mineralogy of pre-, syn-, and postimpact rocks. Compared to its amount of pure, stoichiometric shocked magnetite, the granitoid basement shows low magnetic susceptibility, which is in line with earlier experimental studies indicating that shock reduces magnetic susceptibility. Cation-substituted magnetite with varying compositions in the melt rocks carries a higher induced and remanent magnetization compared to the basement. In the granitoid basement, magnetite was partially oxidized to hematite by a pre-impact hydrothermal event, but at lithological contacts with high-temperature impact melt rock, this hematite was locally retransformed back to magnetite. Elsewhere in the granitoid basement, the temperature reached in the hydrothermal system was too low for hematite retransformation. It was also too low to anneal all the lattice defects in the shocked magnetite, which likely occurs above 540 °C. The presence of shocked magnetite in the granitoid basement well explains the magnetic anomaly low due to its unusually low induced magnetization.
Supplemental Material: Crustal architectural controls on critical metal ore systems in South China based on Hf isotopic mapping
Authors: Zhang Zhiyu , Hou Zengqian , al. et
Published: May 2023

Methodology, supporting maps and diagrams (Figs. S1–S6), and primitive data tables (Tables S1–S2).  
Unusual association of torticollis with Russell-Silver syndrome
Authors: Kaggare Puttaraju Mahesh , Manjunatha Bhari Sharanesha , Patil Karthikeya , Kaiyoor Lakshminarayana Surya
Published: May 2023

Russell-Silver syndrome is a unique disorder characterised by intrauterine growth retardation before and after birth, large-sized head, a triangular facial appearance, a protuberant forehead, asymmetry and feeding difficulties. This extensive spectrum of features varies in both occurrence and gravity from one individual to another. Congenital muscular torticollis or commonly known as wry neck is one of the common presenting complaints in the outpatient department. It is characterised by rotational deformity of the cervical spine and consequently secondary tilting of the head.
Iris volume change with physiologic mydriasis to identify development of angle closure: the Zhongshan Angle Closure Prevention Trial
Authors: Liao Chimei , Quigley Harry , Jiang Yuzhen , Huang Shengsong , Huang Wenyong , Friedman David , Foster Paul J , He Mingguang
Published: May 2023

Aims

To assess dynamic change of iris area (Iarea) and volume (VOL) with physiologic pupil dilation for progression of primary angle closure suspects.

Methods

Participants underwent baseline examinations including gonioscopy and anterior segment OCT (AS-OCT) as part of the Zhongshan Angle Closure Prevention Trial. The AS-OCT images were obtained both in the dark and light. Progression was defined as development of primary angle closure or an acute angle closure attack. Static ocular biometrics and dynamic changes were compared between progressors and non-progressors and multivariable logistic regression was developed to assess risk factors for progression.

Results

A mean 16.8% decrease in Iarea and a mean 6.26% decrease in VOL occurred with pupil dilation, while 22.96% non-progressors and 40% progressors presented VOL increases with pupil dilation. Iarea in light and dark and VOL in light were significantly smaller in progressors. In a multivariable logistic model, older age (p=0.008), narrower horizontal angle opening distance (AOD) 250 µm from the scleral spur (AOD250, p=0.001), flatter iris curvature (IC, p=0.006) and lower loss of iris volume (ΔVOL, p=0.04) were significantly associated with progression. With receiver operating characteristic analysis, the area under the curve for ΔVOL alone was 0.621, while that for the combined index (age, AOD250, IC and ΔVOL) was 0.824. Eyes with elevated intraocular pressure had less VOL loss compared with progressors developing peripheral anterior synechiae alone (p=0.055 for ΔVOL adjusted for pupil enlargement).

Conclusion

A smaller change in ΔVOL is an additive risk factor to identify eyes more likely to develop angle closure disease.

Trial registration number

ISRCTN45213099.
Quality in colonoscopy: time to ensure national standards are implemented?
Authors: Neilson Laura J , Dew Rosie , Hampton James S , Sharp Linda , Rees Colin J
Published: May 2023

Background

High-quality colonoscopy is crucial to ensure complete mucosal visualisation and to maximise detection of pathology. Previous audits showing variable quality have prompted national and international colonoscopy improvement programmes, including the development of quality assurance standards and key performance indicators (KPIs). The most widely used marker of mucosal visualisation is the adenoma detection rate (ADR), however, histological confirmation is required to calculate this. We explored the relationship between core colonoscopy KPIs.

Methods

Data were collected from colonoscopists in eight hospitals in North East England over a 6-month period, as part of a quality improvement study. Procedural information was collected including number of colonoscopies, caecal intubation rate (CIR), ADR and polyp detection rate (PDR). Associations between KPIs and colonoscopy performance were analysed.

Results

9265 colonoscopies performed by 118 endoscopists were included. Mean ADR and PDR per endoscopist were 16.6% (range 0–36.3, SD 7.4) and 27.2% (range 0–57.5, SD 9.3), respectively. Mean number of colonoscopies conducted in 6 months was 78.5 (range 4–334, SD 61). Mean CIR was 91.2% (range 55.5–100, SD 6.6). Total number of colonoscopies and ADR>15% were significantly associated (p=0.04). Undertaking fewer colonoscopies and using hyoscine butylbromide less frequently was significantly associated with ADR<15%. CIR, endoscopist grade, % male patients, mean patient age and CIR were not significantly related to ADR<15%. In adjusted analyses, factors which affected ADR were PDR and mean patient age.

Conclusion

Colonoscopists who perform fewer than the nationally stipulated minimum of 100 procedures per year had significantly lower ADRs. This study demonstrates that PDR can be used as a marker of ADR; providing age is also considered.
CD71+erythroid cells suppress T-cell effector functions and predict immunotherapy outcomes in patients with virus-associated solid tumors
Authors: Bozorgmehr Najmeh , Okoye Isobel , Mashhouri Siavash , Lu Julia , Koleva Petya , Walker John , Elahi Shokrollah
Published: May 2023

Background

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer. However, only a portion of patients respond to such treatments. Therefore, it remains a prevailing clinical need to identify factors associated with acquired resistance or lack of response to ICIs. We hypothesized that the immunosuppressive CD71+erythroid cells (CECs) within the tumor and/or distant ‘out-of-field’ may impair antitumor response.

Methods

We studied 38 patients with cancer through a phase II clinical trial investigating the effects of oral valproate combined with avelumab (anti-programmed death-ligand 1 (PD-L1)) in virus-associated solid tumors (VASTs). We quantified the frequency/functionality of CECs in blood and biopsies of patients. Also, we established an animal model of melanoma (B16-F10) to investigate the possible effects of erythropoietin (EPO) treatment on anti-PD-L1 therapy.

Results

We found a substantial expansion of CECs in the blood of patients with VAST compared with healthy controls. We noted that the frequency of CECs in circulation was significantly higher at the baseline and throughout the study in non-responders versus responders to PD-L1 therapy. Moreover, we observed that CECs in a dose-dependent manner suppress effector functions of autologous T cells in vitro. The subpopulation of CD45+CECs appears to have a more robust immunosuppressive property compared with their CD45−counterparts. This was illustrated by a stronger expression of reactive oxygen species, PD-L1/PD-L2, and V-domain Ig suppressor of T-cell activation in this subpopulation. Lastly, we found a higher frequency of CECs in the blood circulation at the later cancer stage and their abundance was associated with anemia, and a poor response to immunotherapy. Finally, we report the expansion of CECs in the spleen and tumor microenvironment of mice with melanoma. We found that although CECs in tumor-bearing mice secret artemin, this was not the case for VAST-derived CECs in humans. Notably, our results imply that EPO, a frequently used drug for anemia treatment in patients with cancer, may promote the generation of CECs and subsequently abrogates the therapeutic effects of ICIs (eg, anti-PD-L1).

Conclusions

Our results demonstrate that anemia by the expansion of CECs may enhance cancer progression. Notably, measuring the frequency of CECs may serve as a valuable biomarker to predict immunotherapy outcomes.