bluuebunny/crossref_metadata_2025 huggingface dataset:
Urinary albumin/creatinine ratio tertiles predict risk of diabetic retinopathy progression: a natural history study from the Adolescent Cardio-Renal Intervention Trial (AdDIT) observational cohort
Authors: Benitez-Aguirre Paul Z. , Marcovecchio M. Loredana , Chiesa Scott T. , Craig Maria E. , Wong Tien Y. , Davis Elizabeth A. , Cotterill Andrew , Couper Jenny J. , Cameron Fergus J. , Mahmud Farid H. , Neil H. Andrew W. , Jones Timothy W. , Hodgson Lauren A. B. , Dalton R. Neil , Marshall Sally M. , Deanfield John , Dunger David B. , Donaghue Kim C. ,   on behalf of the Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT)
Published: February 2022

Aims/hypothesis

We hypothesised that adolescents with type 1 diabetes with a urinary albumin/creatinine ratio (ACR) in the upper tertile of the normal range (high ACR) are at greater risk of three-step diabetic retinopathy progression (3DR) independent of glycaemic control.

Methods

This was a prospective observational study in 710 normoalbuminuric adolescents with type 1 diabetes from the non-intervention cohorts of the Adolescent Cardio-Renal Intervention Trial (AdDIT). Participants were classified as ‘high ACR’ or ‘low ACR’ (lowest and middle ACR tertiles) using baseline standardised log10 ACR. The primary outcome, 3DR, was determined from centrally graded, standardised two-field retinal photographs. 3DR risk was determined using multivariable Cox regression for the effect of high ACR, with HbA1c, BP, LDL-cholesterol and BMI as covariates; diabetes duration was the time-dependent variable.

Results

At baseline mean ± SD age was 14.3 ± 1.6 years and mean ± SD diabetes duration was 7.2 ± 3.3 years. After a median of 3.2 years, 83/710 (12%) had developed 3DR. In multivariable analysis, high ACR (HR 2.1 [1.3, 3.3], p=0.001), higher mean IFCC HbA1c (HR 1.03 [1.01, 1.04], p=0.001) and higher baseline diastolic BP SD score (HR 1.43 [1.08, 1.89], p=0.01) were independently associated with 3DR risk.

Conclusions/interpretation

High ACR is associated with greater risk of 3DR in adolescents, providing a target for future intervention studies.

Trial registration

isrctn.org ISRCTN91419926.

Graphical abstract
Comparable results between crosslinked polyethylene and conventional ultra-high molecular weight polyethylene implanted in total knee arthroplasty: systematic review and meta-analysis of randomised clinical trials
Authors: Bistolfi Alessandro , Giustra Fortunato , Bosco Francesco , Faccenda Carlotta , Viotto Marianna , Sabatini Luigi , Berchialla Paola , Sciannameo Veronica , Graziano Eugenio , Massè Alessandro
Published: February 2022

Purpose

Total knee arthroplasty (TKA) has experienced exponential growth over the last decade, including increasingly younger patients with high functional demands. Highly crosslinked polyethylene (HXLPE) has been proven effective in reducing osteolysis and loosening revisions while improving long-term survival and performance in total hip arthroplasty; nevertheless, this superiority is not demonstrated in TKA. The aim of this systematic review and meta-analysis was to examine whether HXLPE improved overall survival and postoperative functional and radiological outcomes compared to conventional polyethylene (CPE) in TKA.

Methods

According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline, a literature search of five databases (PubMed, Medline, Scopus, Science Direct and Embase) was made. A PICOS model was performed. The initial screening identified 2541 studies. Each eligible clinical article was analysed according to the Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence (LoE). Only randomised clinical trials (RCTs) of LoE 1 and 2 were included. The methodological quality of the articles was assessed using the Risk of Bias 2 (RoB 2) tool.

Results

Six clinical studies were included in the final study. This systematic review and meta-analysis were registered on the International Prospective Register of Systematic Reviews (PROSPERO). A total of 2285 knees were included. Eight outcomes (total reoperations, reoperations for prosthesis loosening and infections, radiolucent lines, osteolysis, mechanical failure, postoperative KSS knee score and function score) were analysed. For none of them, a statistically significant difference was found about the superiority of HXLPE over CPE (p > 0.05).

Conclusions

There were no statistically significant differences between HXLPE and CPE for TKA concerning clinical, radiological, and functional outcomes; nevertheless, HXLPE did not show higher failure rates or complications and can be safely used for TKA.

Level of evidence

II.
Semi-quantitative magnetic resonance imaging scoring of the knee detects previous injuries in professional soccer players
Authors: Welsch Goetz Hannes , Behr Anna-Maria , Frosch Karl-Heinz , Tahir Enver , Pachowsky Milena , Henes Frank Oliver , Adam Gerhard , Maas Kai-Jonathan , Warncke Malte Lennart
Published: February 2022

Purpose

The medical examination (“medical”) is an important procedure in professional soccer since it has high economic relevance. In addition to clinical tests, magnetic resonance imaging (MRI) is used to assess joint health. In the present study, the reliability of semiquantitative knee MRI during the “medical” in professional soccer was tested, and its relationship with clinical data and days missed due to knee injury was observed.

Methods

In this cross-sectional study, between 2012 and 2019, 69 newly assigned players (age 18–35 years) from a professional soccer club underwent MRI (3.0 T) of both knee joints during their “medical”. Reported knee injuries and previously missed days due to injury were obtained from player anamnesis and the “transfermarkt.com” database. Based on the established “Whole-Organ Magnetic Resonance Imaging Score” (WORMS), two independent radiologists graded the MRI results. Further evaluation was based on the mean score of both knees.

Results

The mean WORMS for all subjects was 13.9 (median 10.5, range 0–61). Players with previous injuries had significantly higher scores than players without reported injuries (22.1 ± 17.7 vs. 8.9 ± 4.4, p < 0.002). Three outliers (previously undetected injuries) in the group of players without reported injuries were observed (6.7%). The WORMS was significantly correlated with a prior knee injury (r: 0.424, p < 0.0001) and days missed due to injury (r: 0.489, p < 0.001). Age was correlated with the WORMS (r: 0.386, p < 0.001). In a linear regression model, prior injury was the only significant predictor of a high WORMS (p = 0.001). The WORMS was a significant predictor of days missed due to injury (p < 0.0002) and prior injury (sensitivity: 78%, specificity: 91%, p = 0.006). The intraclass correlation coefficient was excellent (0.89).

Conclusion

Semiquantitative knee MRI for WORMS determination during the soccer “medical” is a robust and reliable method. Prior injury, even in players without documented trauma, was detected by the WORMS, and previously missed days due to injury were correlated with the semiquantitative MR knee score.

Level of evidence

Level III.
Development and implementation of crater and flank tool wear model for hard turning simulations
Authors: Cappellini Cristian , Abeni Andrea
Published: February 2022

This paper concerns the tool wear in hard turning of AISI 52100 hardened steel by means of PCBN tools. The purposes of this work are the development of a tool wear model and its implementation in a FEM-based procedure for predicting crater and flank wear progression during machining operations for studying the influence of tool wear on the process in terms of tool geometry modifications and stress variation on the tool. The developed tool wear model, able to update the geometry of the worn tool as a function of the wear rate, has been implemented in the utilized Deform 2D FEM software. This new analytical model differs from the already proposed methods of existing research, since it concerns both crater and flank wear evaluation. The validation of the model has been achieved by the comparison between experimental and simulated wear parameters. For doing this, an extended experimental campaign has been accomplished. The comparison results have shown good agreement. Once validated, the FEM strategy has been utilized for examining the influence of tool wear on the effective rake angle and the related tool stresses, individuating the excessive positive rake angle value as the final tool breakage mechanism.
Inhibition of neurite outgrowth and enhanced effects compared to baseline toxicity in SH-SY5Y cells
Authors: Lee Jungeun , Escher Beate I. , Scholz Stefan , Schlichting Rita
Published: February 2022

Early life exposure to environmental chemicals can cause developmental neurotoxicity (DNT). The impairment of key neurodevelopmental processes such as neurite outgrowth inhibition can be used as endpoints for screening of DNT effects. We quantified neurite-specific effects using the ratio of effect concentrations for cytotoxicity and neurite outgrowth inhibition (SRcytotoxicity). Baseline cytotoxicity, the minimal toxicity of any chemical, was used to quantify enhanced cytotoxicity (toxic ratio, TR) and neuronal-specific toxicity (SRbaseline) by comparing baseline cytotoxicity with the effects on cell viability and neurite outgrowth, respectively. The effects on cell viability and neurite length were measured based on image analysis in human neuroblastoma SH-SY5Y cells. Baseline cytotoxicity was predicted from hydrophobicity descriptors using a previously published model for SH-SY5Y cells. Enhanced cytotoxicity and neuronal-specific toxicity were more often observed for hydrophilic chemicals, which indicates that they are more likely to act through specific modes of action (MOA) on cell viability and neurite outgrowth. Hydrophobic chemicals showed a tendency to act through baseline toxicity without showing specific or enhanced toxicity, but were highly potent considering their low effect concentrations for both cytotoxicity and neurite outgrowth inhibition. The endpoint-specific controls (narciclasine, colchicine, cycloheximide, and rotenone), two carbamates (3-hydroxycarbofuran and carbaryl), and two redox cyclers (diquat and paraquat) showed distinct neurite-specific effects (SRcytotoxicity > 4). By comparing neurite-specific effects with enhanced cytotoxicity, one can explain whether the observed effects involve specific inhibition of neurite outgrowth, other specific MOAs, or merely baseline toxicity arising from hydrophobicity.
Evaluation and validation of methodologies for the extraction of per- and polyfluoroalkyl substances (PFASs) in serum of birds and mammals
Authors: Szabo Drew , Marchiandi Jaye , Green Mark P. , Mulder Raoul A. , Clarke Bradley O.
Published: February 2022

Advances in analytical techniques have allowed greater detection of environmental contaminants from small volumes of sample. Four methodologies were evaluated for the extraction of 53 per- and polyfluoroalkyl substances (PFASs) from eight classes in 200 µL of avian and mammal serum. Spiked serums at four concentrations (0, 0.5, 5.0 and 25 ng mL−1) were prepared by protein precipitation (PPT), enhanced matrix removal (EMR), weak anion exchange (WAX), and hydrophilic-lipophilic balance (HLB) solid-phase extraction cartridges. The extract from each methodology was analysed by high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC–MS/MS), and concentrations were compared with known concentrations in the spiked media. EMR performed the best overall, with 40 of 53 compounds effectively recovered at 5 ng mL−1. Furthermore, EMR was effective overall at concentrations ranging from 0.5 to 25 ng mL−1for 39 out of 53. Similarly, PPT was effective for 35 of 53 compounds at all spiked serum concentrations. There was a negative correlation between internal standard recovery for compounds with increasing octanol–water coefficients (Kow) for WAX (R =  − 0.65,p = 0.0043) and HLB (R =  − 0.62,p = 0.0077) extractions, indicating methanol may not be a suitable solvent for long-chain PFAS extraction from protein-rich tissues. EMR and PPT represent fast and effective methodologies for the extraction of PFASs from low volumes of serum which allows greater accuracy and precision that can be applied to future human and wildlife biomonitoring programmes.
FFF-based high-throughput sequence shortlisting to support the development of aptamer-based analytical strategies
Authors: Marassi Valentina , Mattarozzi Monica , Toma Lorenzo , Giordani Stefano , Ronda Luca , Roda Barbara , Zattoni Andrea , Reschiglian Pierluigi , Careri Maria
Published: February 2022

Aptamers are biomimetic receptors that are increasingly exploited for the development of optical and electrochemical aptasensors. They are selected in vitro by the SELEX (Systematic Evolution of Ligands by Exponential Enrichment) procedure, but although they are promising recognition elements, for their reliable applicability for analytical purposes, one cannot ignore sample components that cause matrix effects. This particularly applies when different SELEX-selected aptamers and related truncated sequences are available for a certain target, and the choice of the aptamer should be driven by the specific downstream application. In this context, the present work aimed at investigating the potentialities of asymmetrical flow field-flow fractionation (AF4) with UV detection for the development of a screening method of a large number of anti-lysozyme aptamers towards lysozyme, including randomized sequences and an interfering agent (serum albumin). The possibility to work in native conditions and selectively monitor the evolution of untagged aptamer signal as a result of aptamer-protein binding makes the devised method effective as a strategy for shortlisting the most promising aptamers both in terms of affinity and in terms of selectivity, to support subsequent development of aptamer-based analytical devices.

Graphical abstract
Proximate composition and amino acid profile of European eel skin: influence of body weight
Authors: Gómez-Limia Lucía , Carballo Javier , Rodríguez-González Mirian , Martínez Sidonia
Published: February 2022

Fish processing industries worldwide are discarding million kilograms of fish waste per year. The disposal of these wastes is an important handicap in fish processing industry. The thick eel skin is considered a waste product in the fish processing industry and in the home and is usually converted into low market-value products. The aims of this study were to evaluate the variations in the general chemical composition and amino acid content of eel skin in relation to body weight. The moisture content decreased and the lipid content increased with the weight of the eels. Eel skin had a high protein content, which did not vary significantly with eel weight. Glycine was the most abundant amino acid. The predominant essential amino acid was leucine. The smaller eels contained higher levels of threonine, valine, isoleucine, leucine, lysine, glutamic acid and tyrosine than the other groups. The larger eels contained higher levels of methionine, hydroxyproline, glycine, arginine, alanine and proline than the other groups. The protein indices showed that the skin from smaller eels was of higher nutritional quality.

Graphical abstract
Deformations of Half-Sided Modular Inclusions and Non-local Chiral Field Theories
Authors: Lechner Gandalf , Scotford Charley
Published: February 2022

We construct explicit examples of half-sided modular inclusions$$\mathcal {N}\subset \mathcal {M}$$N⊂Mof von Neumann algebras with trivial relative commutants. After stating a general criterion for triviality of the relative commutant in terms of an algebra localized at infinity, we consider a second quantization inclusion$$\mathcal {N}\subset \mathcal {M}$$N⊂Mwith large relative commutant and construct a one-parameter family$$\mathcal {N}_\kappa \subset \mathcal {M}_\kappa $$Nκ⊂Mκ,$$\kappa \ge 0$$κ≥0, of half-sided inclusions such that$$\mathcal {N}_0=\mathcal {N}$$N0=N,$$\mathcal {M}_0=\mathcal {M}$$M0=Mand$$\mathcal {N}_\kappa '\cap \mathcal {M}_\kappa =\mathbb {C}1$$Nκ′∩Mκ=C1for$$\kappa >0$$κ>0. The technique we use is an explicit deformation procedure (warped convolution), and we explain the relation of this result to the construction of chiral conformal quantum field theories on the real line and on the circle.
Cerebral venous sinus thrombosis after adenovirus-vectored COVID-19 vaccination: review of the neurological-neuroradiological procedure
Authors: Wittstock Matthias , Walter Uwe , Volmer Erik , Storch Alexander , Weber Marc-André , Großmann Annette
Published: February 2022

Cerebral venous and sinus thrombosis (CVST) after adenovirus-vectored COVID-19 ChAdOx1 nCov-19 (Oxford–AstraZeneca) and Ad26.COV2.S (Janssen/Johnson & Johnson) is a rare complication, occurring mainly in individuals under 60 years of age and more frequently in women. It manifests 4–24 days after vaccination. In most cases, antibodies against platelet factor-4/polyanion complexes play a pathogenic role, leading to thrombosis with thrombocytopenia syndrome (TTS) and sometimes a severe clinical or even fatal course. The leading symptom is headache, which usually increases in intensity over a few days. Seizures, visual disturbances, focal neurological symptoms, and signs of increased intracranial pressure are also possible. These symptoms may be combined with clinical signs of disseminated intravascular coagulation such as petechiae or gastrointestinal bleeding. If TTS-CVST is suspected, checking d-dimers, platelet count, and screening for heparin-induced thrombocytopenia (HIT-2) are diagnostically and therapeutically guiding. The imaging method of choice for diagnosis or exclusion of CVST is magnetic resonance imaging (MRI) combined with contrast-enhanced venous MR angiography (MRA). On T2*-weighted or susceptibility weighted MR sequences, the thrombus causes susceptibility artefacts (blooming), that allow for the detection even of isolated cortical vein thromboses. The diagnosis of TTS-CVST can usually be made reliably in synopsis with the clinical and laboratory findings. A close collaboration between neurologists and neuroradiologists is mandatory. TTS-CVST requires specific regimens of anticoagulation and immunomodulation therapy if thrombocytopenia and/or pathogenic antibodies to PF4/polyanion complexes are present. In this review article, the diagnostic and therapeutic steps in cases of suspected TTS associated CSVT are presented.
Post-void bladder ultrasound in suspected cauda equina syndrome—data from medicolegal cases and relevance to magnetic resonance imaging scanning
Authors: Todd Nicholas , Dangas Katerina , Lavy Chris
Published: February 2022

Objective

Post-void residual (PVR) scans of less than 200 ml are increasingly being used to rule out the likelihood of cauda equina syndrome (CES) and to delay emergency MRI scanning in suspected cases. This study was done to review a series of 50 MRI confirmed cases of CES and to test the hypothesis that a PVR of less than 200 ml was unlikely to be present.

Methods

Fifty consecutive medicolegal cases involving CES were audited. Records were reviewed to see if PVR scans were done. MRI scans were reviewed, clinical and radiological diagnosis reviewed, and treatment recorded.

Results

Out of 50 CES cases, 26 had had PVR scans. In 14/26 (54%) the PVR scan was ≤ 200 ml. In one case, the CES diagnosis was in question leaving 13/26 (50%) cases where there was a clear clinical and MRI diagnosis of CES despite the PVR being ≤ 200 ml. All 13 were classified as incomplete cauda equina syndrome (CESI) and all proceeded to emergency decompression.

Conclusions

This study is the first in the literature to demonstrate that there is a significant group of CES patients who require emergency decompression but have PVRs ≤ 200 ml.

The results demonstrate the existence of a significant group of CESI patients whose bladder function may be deteriorating, but they have not yet reached the point where the PVR is over 200 ml. Given the accepted understanding that CESI is best treated with emergency decompression, such patients are likely to have worse outcomes if MRI scanning and therefore surgery is delayed. We recommend the following:

PVR is recommended as an assessment tool in suspected CES.

A PVR of ≤ 200 reduces the likelihood of having CES but does not exclude it; clinical suspicion of CES should always lead to an MRI scan.

Further investigation of PVR as a prognostic tool is recommended.
Real-world outcomes in elderly ALL patients with and without allogeneic hematopoietic stem cell transplantation: a single-center evaluation over 10 years
Authors: Hofer Kevin D. , Schanz Urs , Schwotzer Rahel , Nair Gayathri , Manz Markus G. , Widmer Corinne C.
Published: February 2022

Elderly patients (EP) of 60 years and above with acute lymphoblastic leukemia (ALL) have a dismal prognosis, but pediatric-inspired chemotherapy and allogeneic stem cell transplantation (allo HCT) are used reluctantly due to limited data and historical reports of high treatment-related mortality in EP. We analyzed 130 adult ALL patients treated at our center between 2009 and 2019, of which 26 were EP (range 60–76 years). Induction with pediatric-inspired protocols was feasible in 65.2% of EP and resulted in complete remission in 86.7% compared to 88.0% in younger patients (YP) of less than 60 years. Early death occurred in 6.7% of EP. Three-year overall survival (OS) for Ph − B-ALL was significantly worse for EP (n = 16) than YP (n = 64) with 30.0% vs 78.1% (p ≤ 0.001). Forty-nine patients received allo HCT including 8 EP, for which improved 3-year OS of 87.5% was observed, whereas EP without allo HCT died after a median of 9.5 months. In Ph + B-ALL, 3-year OS did not differ between EP (60.0%, n = 7) and YP (70.8%, n = 19). Non-relapse mortality and infection rate were low in EP (14.3% and 12.5%, respectively). Our data indicate that selected EP can be treated effectively and safely with pediatric regimens and might benefit from intensified therapy including allo HCT.
The spectrum of paroxysmal nocturnal hemoglobinuria clinical presentation in a Brazilian single referral center
Authors: Pires da Silva Bruno G. P. , Fonseca Natasha P. , Catto Luis Fernando B. , Pereira Gabriel C. , Calado Rodrigo T.
Published: February 2022

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematological disorder caused by the expansion of a hematopoietic clone harboring a somatic genetic variant in the PIG-A gene translating into a wide spectrum of clinical and laboratory changes, from intravascular hemolysis, thrombosis, and bone marrow failure to subclinical presentation. In this study, we retrospectively analyzed 87 consecutive cases (39 women; median follow-up, 18 months; range, 0–151 months) in whom a PNH clone was detected by flow cytometry between 2006 and 2019 seen at a single Brazilian referral center. The median age at diagnosis was 29 years (range, 8 to 83 years); 29 patients (33%) were initially classified as PNH/bone marrow failure, 13 (15%) as classic PNH, and 45 (52%) as subclinical PNH. The median overall survival (OS) of the entire cohort was not reached during follow-up, without significant differences between groups. At diagnosis, the median PNH clone size was 2.8% (range, 0 to 65%) in erythrocytes and 5.4% (range, 0 to 80%) in neutrophils. Fourteen patients experienced clone expansion during follow-up; in other 14 patients the clone disappeared, and in 18 patients it remained stable throughout the follow-up. A subclinical PNH clone was detected in three telomeropathy patients at diagnosis, but it was persistent and confirmed by DNA sequencing in only one case. In conclusion, PNH presentation was variable, and most patients had subclinical disease or associated with marrow failure and did not require specific anticomplement therapy. Clone size was stable or even disappeared in most cases.
Inclusion of quantitative high-density plaque in coronary computed tomographic score system to predict the time of guidewire crossing chronic total occlusion
Authors: Wang Rui , He Yi , Xing Haoran , Zhang Dongfeng , Tian Jinfan , Le Yinghui , Zhang Lijun , Chen Hui , Song Xiantao , Wang Zhenchang
Published: February 2022

Objective

This study aimed to establish a new scoring system that includes histological quantitative features derived from coronary computed tomographic angiography (CCTA) to predict the efficiency of chronic total occlusion percutaneous coronary intervention (CTO-PCI).

Methods

This study analyzed clinical, morphological, and histological characteristics of 207 CTO lesions in 201 patients (mean age 60.0 [52.0–65.0] years, 85% male), which were recruited from two centers. The primary endpoint was a guidewire successfully crossing the lesions within 30 m. The new predictive model was generated by factors that were determined by multivariate analysis. The CCTA plaque (CTAP) score that included a quantitative plaque characteristic was developed by assigning an appropriate integer score to each independent predictor, then summing all points. In addition, the CTAP score was compared with other predictive scores based on CCTA.

Results

The endpoint was achieved in 63% of the lesions. The independent predictors included previous CTO-PCI failure, the proximal blunt stump, proximal side branch, distal side branch, occluded segment bending > 45°, and high-density plaque volume (fibrous volume + calcified volume) ≥ 19.9 mm3. As the score increased from 0 to 5, the success rate of the guidewire crossing within 30 m decreased from 96 to 0%. Comparing the CTAP score with other predictive scores, the CTAP score showed the highest discriminant power (c-statistic = 0.81 versus 0.73–0.77, p value 0.02–0.07). The CTAP score showed similar results for procedural success.

Conclusion

The CTAP score efficiently predicted the guidewire crossing efficiency and procedural success.

Key Points

• An increase in high-density plaque volume (fibrous + dense calcium) was more probable to reduce the efficiency of crossing and lead to procedural failure.

• The new prediction scoring system with the addition of the quantitative characteristics of plaques had an improved predictive ability compared with the traditional prediction scoring system.
Impact of resolution on the atmosphere–ocean coupling along the Gulf Stream in global high resolution models
Authors: Tsartsali E. E. , Haarsma R. J. , Athanasiadis P. J. , Bellucci A. , de Vries H. , Drijfhout S. , de Vries I. E. , Putrahasan D. , Roberts M. J. , Sanchez–Gomez E. , Roberts C. D.
Published: February 2022

We have investigated the horizontal resolution dependence of the ocean–atmosphere coupling along the Gulf Stream, of simulations made by six Global Climate Models according to the HighResMIP protocol, and compared it with reanalysis and remote sensing observations. Two ocean–atmosphere interaction mechanisms are explored in detail: The Vertical Mixing Mechanism (VMM) associated with the intensification of downward momentum transfer, and the Pressure Adjustment Mechanism (PAM) associated with secondary circulations driven by pressure gradients. Both VMM and PAM are found to be active even in the eddy-parameterized models. However, increasing ocean and/or atmosphere resolution leads to enhanced ocean–atmosphere coupling and improved agreement with reanalysis and observations. Our results indicate that while one part of the stronger air–sea coupling is attributable to the refinement of the oceanic component to eddy-permitting, optimal results are obtained only by further increase of the atmosphere resolution too. The use of the eddy-resolving model show weaker or same coupling strength over the eddy-permitting resolution. We conclude that at least eddy-permiting ocean resolution and comparable atmosphere resolution are required for a reliable ocean–atmosphere coupling along the Gulf Stream.
Co-ingestion of cluster dextrin carbohydrate does not increase exogenous protein-derived amino acid release or myofibrillar protein synthesis following a whole-body resistance exercise in moderately trained younger males: a double-blinded randomized controlled crossover trial
Authors: Nishimura Yusuke , Jensen Mikkel , Bülow Jacob , Thomsen Thomas Tagmose , Arimitsu Takuma , van Hall Gerrit , Fujita Satoshi , Holm Lars
Published: February 2022

Purpose

This study investigates if co-ingestion of cluster dextrin (CDX) augments the appearance of intrinsically labeled meat protein hydrolysate-derived amino acid (D5-phenylalanine), Akt/mTORC1 signaling, and myofibrillar protein fractional synthetic rate (FSR).

Methods

Ten moderately trained healthy males (age: 21.5 ± 2.1 years, body mass: 75.7 ± 7.6 kg, body mass index (BMI): 22.9 ± 2.1 kg/m2) were included for a double-blinded randomized controlled crossover trial. Either 75 g of CDX or glucose (GLC) was given in conjunction with meat protein hydrolysate (0.6 g protein * FFM−1) following a whole-body resistance exercise. A primed-continuous intravenous infusion of L-[15N]-phenylalanine with serial muscle biopsies and venous blood sampling was performed.

Results

A time × group interaction effect was found for serum D5-phenylalanine enrichment (P < 0.01). Serum EAA and BCAA concentrations showed a main effect for group (P < 0.05). Tmax serum BCAA was greater in CDX as compared to GLC (P < 0.05). However, iAUC of all serum parameters did not differ between CDX and GLC (P > 0.05). Tmax serum EAA showed a trend towards a statistical significance favoring CDX over GLC. The phosphorylation of p70S6KThr389, rpS6Ser240/244, ERK1/2Thr202/Tyr204 was greater in CDX compared to GLC (P < 0.05). However, postprandial myofibrillar FSR did not differ between CDX and GLC (P = 0.17).

Conclusion

In moderately trained younger males, co-ingestion of CDX with meat protein hydrolysate does not augment the postprandial amino acid availability or myofibrillar FSR as compared to co-ingestion of GLC during the recovery from a whole-body resistance exercise despite an increased intramuscular signaling.

Trial registration

ClinicalTrials.gov ID: NCT03303729 (registered on October 3, 2017).
Morphological characterization reveals new insights into giant cell development of Meloidogyne graminicola on rice
Authors: Niu Yongrui , Xiao Liying , de Almeida-Engler Janice , Gheysen Godelieve , Peng Deliang , Xiao Xueqiong , Huang Wenkun , Wang Gaofeng , Xiao Yannong
Published: February 2022

Main conclusion

Three types of nematode-feeding sites (NFSs) caused by M. graminicola on rice were suggested, and the NFS polarized expansion stops before the full NFS maturation that occurs at adult female stage.

Root-knot nematodes, Meloidogyne spp., secrete effectors and recruit host genes to establish their feeding sites giant cells, ensuring their nutrient acquisition. There is still a limited understanding of the mechanism underlying giant cell development. Here, the three-dimensional structures of M. graminicola-caused nematode-feeding sites (NFSs) on rice as well as changes in morphological features and cytoplasm density of the giant cells (GCs) during nematode parasitism were reconstructed and characterized by confocal microscopy and the Fiji software. Characterization of morphological features showed that three types of M. graminicola-caused NFSs, type I–III, were detected during parasitism at the second juvenile (J2), the third juvenile (J3), the fourth juvenile (J4) and adult female stages. Type I is the majority at all stages and type II develops into type I at J3 stage marked by its longitudinal growth. Meanwhile, NFSs underwent polarized expansion, where the lateral and longitudinal expansion ceased at later parasitic J2 stage and the non-feeding J4 stage, respectively. The investigation of giant cell cytoplasm density indicates that it reaches a peak at the midpoint of early parasitic J2 and adult female stages. Our data suggest the formation of three types of NFSs caused by M. graminicola on rice and the NFS polarized expansion stopping before full NFS maturation, which provides unprecedented spatio-temporal characterization of development of giant cells caused by a root-knot nematode.
Postoperative delirium is an independent factor influencing the length of stay of elderly patients in the intensive care unit and in hospital
Authors: Kirfel Andrea , Guttenthaler Vera , Mayr Andreas , Coburn Mark , Menzenbach Jan , Wittmann Maria
Published: February 2022

Purpose

Postoperative delirium (POD) is an often unrecognized adverse event in older people after surgery. The aim of this subgroup analysis of the PRe-Operative Prediction of postoperative DElirium by appropriate SCreening (PROPDESC) trial in patients aged 70 years and older was to identify preoperative risk factors and the impact of POD on length of stay (LOS) in intensive care unit (ICU) and hospital.

Methods

Of the total 1097 patients recruited at a German university hospital (from September 2018 to October 2019) in the PROPDESC prospective observational study, 588 patients aged 70 years and older (mean age 77.2 ± 4.7 years) were included for subgroup analysis. The primary endpoint POD was considered positive if one of the following tests were positive on any of the five postoperative visit days: Confusion Assessment Method for ICU (CAM-ICU), Confusion Assessment Method (CAM), 4'A's (4AT) and Delirium Observation Scale (DOS). Trained doctoral students carried out these visitations and additionally the nursing staff were interviewed for completion of the DOS. To evaluate the independent effect of POD on LOS in ICU and in hospital, a multi-variable linear regression analysis was performed.

Results

The POD incidence was 25.9%. The results of our model showed POD as an independent predictor for a prolonged LOS in ICU (36%; 95% CI 4–78%; < 0.001) and in hospital (22%; 95% CI 4–43%; < 0.001).

Conclusion

POD has an independent impact on LOS in ICU and in hospital. Based on the effect of POD for the elderly, a standardized risk screening is required.

Trail registration

German Registry for Clinical Studies: DRKS00015715.
True Mode $$\mathrm {III}$$ Fracturing of Rocks: An Axially Double-Edge Notched Brazilian Disk Test
Authors: Bahrami Bahador , Nejati Morteza , Ayatollahi Majid Reza , Driesner Thomas
Published: February 2022

A new test, referred to as axially double-edge notched Brazilian disk (ANBD), is proposed to measure true mode $$\mathrm {III}$$
III
fracture toughness ($$K_{\mathrm {IIIc}}$$

K
IIIc

) of rock materials. The term true denotes a shear-induced fracturing via self-planar crack extension as opposed to a twisted tension-based one commonly observed in many mode $$\mathrm {III}$$
III
experiments of rocks. The ANBD test follows a straightforward procedure thanks to its simple core-based geometry and diametrical compression loading setup. Finite element analyses are employed to evaluate the stress intensity variations along the crack front and to calculate the point-wise stress intensity factors (SIFs) for different geometry and loading configurations. The results of ANBD tests conducted on granitic samples demonstrate the good performance of this test in yielding true mode $$\mathrm {III}$$
III
fracturing. The influences of the test parameters of ligament length and loading angle on $$K_{\mathrm {IIIc}}$$

K
IIIc

are also investigated. A comparison study shows that $$K_{\mathrm {IIIc}}$$

K
IIIc

values are similar to $$K_{\mathrm {IIc}}$$

K
IIc

but almost 2.5 times greater than $$K_{\mathrm {Ic}}$$

K
Ic

. This demonstrates that the true mode $$\mathrm {III}$$
III
test offers a similar shear-based fracturing mechanism to the true mode $$\mathrm {II}$$
II
, which is significantly more energy-consuming than the tension-based mode $$\mathrm {I}$$
I
failure type.
Long-term regional changes in inter-annual precipitation variability in the Campania Region, Southern Italy
Authors: Longobardi Antonia , Boulariah Ouafik
Published: February 2022

Precipitation variability in space and time has been a focus of research over the past decades. The largest body of literature was essentially focused on long-term changes in average climates and in climate extremes. Analyses of the changes in the inter-annual climate variability (the year-to-year variability), which represent an index of climatic risk, received instead very less attention, but it represents an important issue in order to quantitatively measure the socioeconomic impact of climate change impact over water resources. In order to depict a general characterization of the long-term climate variability for the Campania region, located in Southern Italy within the Mediterranean basin, an analysis of the precipitation coefficient of variation, assumed as an index of inter-annual climate variability, was performed over the period 1918–2015 and compared with the annual precipitation regime and the intra-annual precipitation variability of the same region. The Mann–Kendall and the modified Mann–Kendall tests were applied to detect the sign and significance of the temporal changes and Sen’s test was applied to quantify the temporal changes in inter-annual variability. The results illustrated a generalized condition (73% of total stations) of statistically significant increase of inter-annual variability distributed almost over the whole analyzed area, even though the detected change appeared rather moderate in magnitude. The relationship between annual precipitation, intra-annual precipitation variability, and inter-annual precipitation variability was not clearly identified for the studied region, likely because of the characteristics of climatic homogeneity for the area under investigation. However, the comparative analyzes clearly showed how, if the variations in the annual precipitation regime and in the intra-annual precipitation variability are poorly significant (respectively for 9% and 11% of total station), changes in inter-annual precipitation variability are strongly marked over the studied region.
Drought propagation in the hydrological cycle in a semiarid region: a case study in the Bilate catchment, Ethiopia
Authors: Wossenyeleh Buruk Kitachew , Kasa Ayalew Shura , Verbeiren Boud , Huysmans Marijke
Published: February 2022

Drought is a temporal decrease in water availability and occurs in all climatic regions. Droughts propagate through the hydrological cycle, e.g., meteorological drought propagates to groundwater recharge drought. This research investigated drought propagation in the hydrological cycle in a semiarid context. Meteorological drought severity was determined using a standardized precipitation index (SPI). A variable threshold method and standardized groundwater index (SGI) was implemented to investigate groundwater recharge drought. Comparing meteorological drought (SPI) and groundwater drought (SGI) helps to assess drought propagation in the hydrological cycle. For drought analysis, time-series of rainfall and groundwater recharge needs to be available with high spatial and temporal resolution. Therefore, for this study, daily rainfall measurements were collected from 11 meteorological stations, and water balance modeling was used to estimate temporally and spatially distributed groundwater recharge. This research was carried out in the Bilate River catchment in the Rift Valley basin of Ethiopia. Results show that meteorological droughts were observed before every groundwater recharge drought and they propagate to groundwater recharge drought. Furthermore, analysis of the drought propagation indicates that not all meteorological droughts are propagated. The analysis also shows that a combination of mild to severe meteorological droughts can propagate to groundwater recharge and result in a major groundwater-recharge drought event.
Spatiotemporal high-resolution prediction and mapping: methodology and application to dengue disease
Authors: Jaya I. Gede Nyoman Mindra , Folmer Henk
Published: February 2022

Dengue disease has become a major public health problem. Accurate and precise identification, prediction and mapping of high-risk areas are crucial elements of an effective and efficient early warning system in countering the spread of dengue disease. In this paper, we present the fusion area-cell spatiotemporal generalized geoadditive-Gaussian Markov random field (FGG-GMRF) framework for joint estimation of an area-cell model, involving temporally varying coefficients, spatially and temporally structured and unstructured random effects, and spatiotemporal interaction of the random effects. The spatiotemporal Gaussian field is applied to determine the unobserved relative risk at cell level. It is transformed to a Gaussian Markov random field using the finite element method and the linear stochastic partial differential equation approach to solve the “big n” problem. Sub-area relative risk estimates are obtained as block averages of the cell outcomes within each sub-area boundary. The FGG-GMRF model is estimated by applying Bayesian Integrated Nested Laplace Approximation. In the application to Bandung city, Indonesia, we combine low-resolution area level (district) spatiotemporal data on population at risk and incidence and high-resolution cell level data on weather variables to obtain predictions of relative risk at subdistrict level. The predicted dengue relative risk at subdistrict level suggests significant fine-scale heterogeneities which are not apparent when examining the area level. The relative risk varies considerably across subdistricts and time, with the latter showing an increase in the period January–July and a decrease in the period August–December.
Performance evaluation of machine learning for fault selection in power transmission lines
Authors: Gutierrez-Rojas Daniel , Christou Ioannis T. , Dantas Daniel , Narayanan Arun , Nardelli Pedro H. J. , Yang Yongheng
Published: February 2022

Learning methods have been increasingly used in power engineering to perform various tasks. In this paper, a fault selection procedure in double-circuit transmission lines employing different learning methods is accordingly proposed. In the proposed procedure, the discrete Fourier transform (DFT) is used to pre-process raw data from the transmission line before it is fed into the learning algorithm, which will detect and classify any fault based on a training period. The performance of different machine learning algorithms is then numerically compared through simulations. The comparison indicates that an artificial neural network (ANN) achieves remarkable accuracy of 98.47%. As a drawback, the ANN method cannot provide explainable results and is also not robust against noisy measurements. Subsequently, it is demonstrated that explainable results can be obtained with high accuracy by using rule-based learners such as the recently developed quantitative association rule mining algorithm (QARMA). The QARMA algorithm outperforms other explainable schemes, while attaining an accuracy of 98%. Besides, it was shown that QARMA leads to a very high accuracy of 97% for highly noisy data. The proposed method was also validated using data from an actual transmission line fault. In summary, the proposed two-step procedure using the DFT combined with either deep learning or rule-based algorithms can accurately and successfully perform fault selection tasks but indicating remarkable advantages of the QARMA due to its explainability and robustness against noise. Those aspects are extremely important if machine learning and other data-driven methods are to be employed in critical engineering applications.
First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in advanced non-small cell lung cancer: a subanalysis of Asian patients in CheckMate 9LA
Authors: John Thomas , Sakai Hiroshi , Ikeda Satoshi , Cheng Ying , Kasahara Kazuo , Sato Yuki , Nakahara Yoshiro , Takeda Masayuki , Kaneda Hiroyasu , Zhang Helong , Maemondo Makoto , Minato Koichi , Hisada Takeshi , Misumi Yuki , Satouchi Miyako , Hotta Katsuyuki , Li Ang , Oukessou Abderrahim , Lu Shun
Published: February 2022

Background

CheckMate 9LA, a phase 3, randomized, open-label study in first-line advanced non-small cell lung cancer (NSCLC), showed significantly improved overall survival (OS) with nivolumab plus ipilimumab combined with 2 cycles of chemotherapy versus chemotherapy alone (4 cycles). We present results for the Asian subpopulation enrolled in Japan and China.

Methods

Patients aged ≥ 18 years with treatment-naive, histologically confirmed stage IV or recurrent NSCLC, Eastern Cooperative Oncology Group performance status 0–1 and no sensitizing EGFR/ALK mutations were randomized 1:1 to nivolumab [360 mg every 3 weeks (Q3W)] plus ipilimumab (1 mg/kg Q6W) combined with chemotherapy (Q3W for 2 cycles), or chemotherapy alone (Q3W for 4 cycles). Primary endpoint was OS; secondary endpoints included progression-free survival (PFS) and objective response rate (ORR).

Results

Twenty-eight patients received nivolumab plus ipilimumab combined with chemotherapy and 30 received chemotherapy. At a minimum follow-up of 12.7 months, median OS was not reached with nivolumab plus ipilimumab combined with chemotherapy versus 13.3 months with chemotherapy [hazard ratio (HR) 0.33; 95% confidence interval (CI) 0.14–0.80]. Median PFS was 8.4 versus 5.4 months (HR 0.47; 95% CI 0.24–0.92) and ORR was 57% versus 23%, respectively. Grade 3–4 treatment-related adverse events were observed in 57% versus 60% of patients, respectively.

Conclusion

Consistent with results in the all randomized population, nivolumab plus ipilimumab combined with chemotherapy improved efficacy in the Asian subpopulation versus chemotherapy alone and had a manageable safety profile, supporting its use as first-line treatment for advanced NSCLC in Asian patients.
Effectiveness of neutralizing antibody cocktail in hemodialysis patients: a case series of 20 patients treated with or without REGN-COV2
Authors: Arikawa Shigehisa , Fukuoka Kazuhito , Nakamoto Keitaro , Kunitomo Rie , Matsuno Yuki , Shimazaki Teppei , Saraya Takeshi , Kawakami Takahisa , Kishimoto Mitsumasa , Komagata Yoshinori , Kurai Daisuke , Ishi Haruyuki , Kaname Shinya
Published: February 2022

The number of patients with SARS-CoV-2 infection continues to increase, and it has become a global pandemic. Although there is an urgent need to establish an effective treatment, the medication available for dialysis patients has been limited. An antibody cocktail containing two SARS-CoV-2-neutrarizing antibodies, REGN-COV2 has been granted special approval for COVID-19 in Japan, since July 2021, and this intravenous preparation can be used for dialysis patients. At our hospital, we had 22 hemodialysis patients with COVID-19, and five of them were treated with REGN-COV2. On admission, four of the five patients had moderate disease (pneumonia but O2 inhalation) and one patient had mild disease (not having pneumonia). The mean duration of hospitalization treated with REGN-COV2 was 10.2 ± 2.86 days (mean ± SD), which was less than half, compared to patients untreated of similar severity on admission (22.12 ± 15.5). The time to fever resolution was average 7 days, and no cases progressed to severe illness or death. Among these patients, no obvious adverse reactions were shown. Although more studies with a larger number of patients could be needed for a rigorous evaluation of the effect, our result suggests that REGN-COV2 may be safe and having the possibilities in preventing severe disease in hemodialysis patients. Given the difficulty in securing inpatient beds tend to be in short supply, the strategy combined with neutralizing antibody could be beneficial for end-stage kidney disease (ESKD) patients with hemodialysis who are at high risk of severe disease.