bluuebunny/crossref_metadata_2025 huggingface dataset:
An antibody-free LC-MS/MS method for the quantification of intact insulin-like growth factors 1 and 2 in human plasma
Authors: Pratt Mark S. , van Faassen Martijn , Remmelts Noah , Bischoff Rainer , Kema Ido P.
Published: February 2021

Insulin-like growth factors 1 and 2 (IGF-1 and IGF-2) are important biomarkers in research and diagnosis of growth disorders. Quantitative analysis is performed using various ligand-binding assays or enzymatic digestion LC-MS/MS methods, whose widespread adoption is hampered by time-consuming sample preparation procedures. We present a simple and fast antibody-free LC-MS/MS method for the quantification of intact IGF-1 and IGF-2 in human plasma. The method requires 50 μL of plasma and uses fully 15N-labelled IGF-1 as internal standard. It features trifluoroethanol (TFE)-based IGF/IGF-binding protein complex dissociation and a two-step selective protein precipitation workflow, using 5% acetic acid in 80/20 acetone/acetonitrile (precipitation 1) and ice-cold ethanol (precipitation 2). Detection of intact IGF-1 and IGF-2 is performed by means of a Waters XEVO TQ-S triple quadrupole mass spectrometer in positive electrospray ionisation (ESI+) mode. Lower limits of quantification were 5.9 ng/mL for IGF-1 and 8.4 ng/mL for IGF-2. Intra-assay imprecision was below 4.5% and inter-assay imprecision was below 5.8% for both analytes. An excellent correlation was found between nominal and measured concentrations of the WHO reference standard for IGF-1. Comparison with the IDS-iSYS IGF-1 immunoassay showed good correlation (R2 > 0.97), although a significant bias was observed with the immunoassay giving substantially higher concentrations. The LC-MS/MS method described here allows for reliable and simultaneous quantification of IGF-1 and IGF-2 in plasma, without the need for enzymatic digestion. The method can be readily implemented in clinical mass spectrometry laboratories and has the potential to be adapted for the analysis of different similarly sized peptide hormones.

Graphical abstract
Predictive performance of parent-metabolite population pharmacokinetic models of (S)-ketamine in healthy volunteers
Authors: Otto M. E. , Bergmann K. R. , Jacobs G. , van Esdonk Michiel J.
Published: February 2021

Purpose

The recent repurposing of ketamine as treatment for pain and depression has increased the need for accurate population pharmacokinetic (PK) models to inform the design of new clinical trials. Therefore, the objectives of this study were to externally validate available PK models on (S)-(nor)ketamine concentrations with in-house data and to improve the best performing model when necessary.

Methods

Based on predefined criteria, five models were selected from literature. Data of two previously performed clinical trials on (S)-ketamine administration in healthy volunteers were available for validation. The predictive performances of the selected models were compared through visual predictive checks (VPCs) and calculation of the (root) mean (square) prediction errors (ME and RMSE). The available data was used to adapt the best performing model through alterations to the model structure and re-estimation of inter-individual variability (IIV).

Results

The model developed by Fanta et al. (Eur J Clin Pharmacol 71:441–447, 2015) performed best at predicting the (S)-ketamine concentration over time, but failed to capture the (S)-norketamine Cmax correctly. Other models with similar population demographics and study designs had estimated relatively small distribution volumes of (S)-ketamine and thus overpredicted concentrations after start of infusion, most likely due to the influence of circulatory dynamics and sampling methodology. Model predictions were improved through a reduction in complexity of the (S)-(nor)ketamine model and re-estimation of IIV.

Conclusion

The modified model resulted in accurate predictions of both (S)-ketamine and (S)-norketamine and thereby provides a solid foundation for future simulation studies of (S)-(nor)ketamine PK in healthy volunteers after (S)-ketamine infusion.
A first-in-human study of 11C-MTP38, a novel PET ligand for phosphodiesterase 7
Authors: Kubota Manabu , Seki Chie , Kimura Yasuyuki , Takahata Keisuke , Shimada Hitoshi , Takado Yuhei , Matsuoka Kiwamu , Tagai Kenji , Sano Yasunori , Yamamoto Yasuharu , Okada Maki , Kikuchi Tatsuya , Ichise Masanori , Kawamura Kazunori , Zhang Ming-Rong , Higuchi Makoto
Published: February 2021

Purpose

Phosphodiesterase 7 (PDE7) is an enzyme that selectively hydrolyses cyclic adenosine monophosphate, and its dysfunction is implicated in neuropsychiatric diseases. However, in vivo visualization of PDE7 in human brains has hitherto not been possible. Using the novel PET ligand 11C-MTP38, which we recently developed, we aimed to image and quantify PDE7 in living human brains.

Methods

Seven healthy males underwent a 90-min PET scan after injection of 11C-MTP38. We performed arterial blood sampling and metabolite analysis of plasma in six subjects to obtain a metabolite-corrected input function. Regional total distribution volumes (VTs) were estimated using compartment models, and Logan plot and Ichise multilinear analysis (MA1). We further quantified the specific radioligand binding using the original multilinear reference tissue model (MRTMO) and standardized uptake value ratio (SUVR) method with the cerebellar cortex as reference.

Results

PET images with 11C-MTP38 showed relatively high retentions in several brain regions, including in the striatum, globus pallidus, and thalamus, as well as fast washout from the cerebellar cortex, in agreement with the known distribution of PDE7. VT values were robustly estimated by two-tissue compartment model analysis (mean VT = 4.2 for the pallidum), Logan plot, and MA1, all in excellent agreement with each other, suggesting the reversibility of 11C-MTP38 binding. Furthermore, there were good agreements between binding values estimated by indirect method and those estimated by both MRTMO and SUVR, indicating that these methods could be useful for reliable quantification of PDE7. Because MRTMO and SUVR do not require arterial blood sampling, they are the most practical for the clinical use of 11C-MTP38-PET.

Conclusion

We have provided the first demonstration of PET visualization of PDE7 in human brains. 11C-MTP38 is a promising novel PET ligand for the quantitative investigation of central PDE7.
Structured and Systematic Team and Procedure Training in Severe Trauma: Going from ‘Zero to Hero’ for a Time‐Critical, Low‐Volume Emergency Procedure Over Three Time Periods
Authors: Meshkinfamfard Maryam , Narvestad Jon Kristian , Wiik Larsen Johannes , Kanani Arezo , Vennesland Jørgen , Reite Andreas , Vetrhus Morten , Thorsen Kenneth , Søreide Kjetil
Published: February 2021

Background

Resuscitative emergency thoracotomy is a potential life‐saving procedure but is rarely performed outside of busy trauma centers. Yet the intervention cannot be deferred nor centralized for critically injured patients presenting in extremis. Low‐volume experience may be mitigated by structured training. The aim of this study was to describe concurrent development of training and simulation in a trauma system and associated effect on one time‐critical emergency procedure on patient outcome.

Methods

An observational cohort study split into 3 arbitrary time‐phases of trauma system development referred to as ‘early’, ‘developing’ and ‘mature’ time‐periods. Core characteristics of the system is described for each phase and concurrent outcomes for all consecutive emergency thoracotomies described with focus on patient characteristics and outcome analyzed for trends in time.

Results

Over the study period, a total of 36 emergency thoracotomies were performed, of which 5 survived (13.9%). The “early” phase had no survivors (0/10), with 2 of 13 (15%) and 3 of 13 (23%) surviving in the development and mature phase, respectively. A decline in ‘elderly’ (>55 years) patients who had emergency thoracotomy occurred with each time period (from 50%, 31% to 7.7%, respectively). The gender distribution and the injury severity scores on admission remained unchanged, while the rate of patients with signs on life (SOL) increased over time.

Conclusion

The improvement over time in survival for one time‐critical emergency procedure may be attributed to structured implementation of team and procedure training. The findings may be transferred to other low‐volume regions for improved trauma care.
Short‐Term Outcomes from a Randomized Screening Phase II Non‐inferiority Trial Comparing Omentectomy and Omentum Preservation for Locally Advanced Gastric Cancer: the TOP‐G Trial
Authors: Murakami Hitoshi , Yamada Takanobu , Taguri Masataka , Hasegawa Shinichi , Yamanaka Takeharu , Rino Yasushi , Mushiake Hiroyuki , Oshima Takashi , Matsukawa Hiroshi , Tani Kazuyuki , Suzuki Yoshihiro , Ozawa Yukihiro , Tanabe Hiroyasu , Osaragi Tomohiko , Sato Tsutomu , Tamagawa Hiroshi , Yukawa Norio , Yoshikawa Takaki , Imada Toshio , Masuda Munetaka , Yamamoto Yuji
Published: February 2021

Background

Omentectomy is considered an essential part of curative gastrectomy for locally advanced gastric cancer (GC), albeit without solid evidence. We conducted a randomized phase II trial (the TOP‐G trial) comparing omentectomy and omentum preservation for gastric cancer. This report describes the short‐term findings regarding the trial's secondary endpoints.

Methods

The trial protocol was submitted to the University Hospital Medical Information Network Clinical Trials Registry (http://www.umin.ac.jp/ctr/: UMIN000005421). The key eligibility criteria were histologically confirmed cT2–4a and N0–2 gastric adenocarcinoma. Short‐term surgical outcomes, including morbidity and mortality, were compared between the omentectomy group (group A, control arm) and the omentum‐preserving surgery group (group B, test arm). All procedures were performed via an open approach. Based on a non‐inferiority margin of 7%, statistical power of 0.7, and type I error of 0.2, the sample size was set to 250 patients.

Results

A total of 251 patients were eligible and randomized (group A: 125 patients, group B: 126 patients) between April 2011 and October 2018. After excluding patients who had peritoneal metastasis or laparotomy history, safety outcomes were analyzed for 247 patients. Group A had a significantly longer median operation time (225 min vs. 204 min, p = 0.022) and tended to have greater median blood loss (260 mL vs. 210 mL p = 0.073). The incidences of morbidity were similar and < 10% in both groups (8% vs. 9%, p = 1.000). There was no mortality in either group.

Conclusions

Operative risk was generally similar between omentectomy and omentum‐preserving surgery for locally advanced gastric cancer.
Influence of the population spatial structure on seed rain distribution of an invasive plant under harsh environment
Authors: Galera Halina , Rudak Agnieszka , Pielech Małgorzata , Znój Anna , Chwedorzewska Katarzyna J. , Wódkiewicz Maciej
Published: February 2021

Distribution of seeds of an invasive species is important for the spread of the invasion and for any directed eradication action. This distribution is driven by seed rain. We studied the influence of tussocks on the spatial pattern of seed rain and resulting population spatial pattern of an invasive Antarctic Poa annua L. population. Our hypothesis was that the tussocks trap wind-dispersed seeds. We set 40 artificial grass seed traps simulating tussocks and 40 soil seed traps (control) in the area occupied by the population. The traps were exposed for a total of 3 years and exchanged periodically. We assessed the seed bank in soil extracted for installation of our control traps. Seed number was determined by the germination method. We did not find any significant difference between the types of traps regarding the number of trapped seeds and the number of traps containing seeds, however trapping events were greater for artificial grass traps. The average size of the seed rain was 13.5 seeds m−2 year−1 and the size of the soil seed bank was 216 seeds m−2. We estimated that accumulation of the soil seed bank required around 16 years. Artificial grass discs may be more efficient than bare soil in accumulating seeds, therefore grass tussocks may influence the spatial population structure not only through local seed deposition, but also by intercepting seeds dispersed by wind. Our research further supports, that directed soil removal from underneath the tussocks is the most efficient eradication method of P. annua in Antarctica.
2D Euler Equations with Stratonovich Transport Noise as a Large-Scale Stochastic Model Reduction
Authors: Flandoli Franco , Pappalettera Umberto
Published: February 2021

The limit from an Euler-type system to the 2D Euler equations with Stratonovich transport noise is investigated. A weak convergence result for the vorticity field and a strong convergence result for the velocity field are proved. Our results aim to provide a stochastic reduction of fluid-dynamics models with three different time scales.
Retrospective German claims data study on initial treatment of bladder carcinoma (BCa) by transurethral bladder resection (TURB): a comparative analysis of costs using standard white light- (WL-) vs. blue light- (BL-) TURB
Authors: Todenhöfer Tilman , Maas Moritz , Ketz Miriam , Kossack Nils , Colling Christiane , Qvick Bryan , Stenzl Arnulf
Published: February 2021

Purpose

Photodynamic diagnosis using hexaminolevulinate (HAL)—guided BL-TURB may reduce the recurrence risk in non-muscle invasive BCa compared to standard WL-TURB due to more sensitive tumor detection. The impact of the initial use of WL- vs. BL-TURB on follow-up costs was evaluated in this real-world data analysis.

Methods

Anonymous claims data of German statutory health insurances (GKV) from 2011 to 2016 were analyzed in a primary and adjusted study population. Selection criteria included five quarters before enrolment, one index quarter (InQ) of initial TURB and BCa diagnosis, either within two years for the primary analysis or within four years for the adjusted analysis, and a follow-up period (FU) of either eleven or three quarters, respectively.

Results

In the primary analysis (n = 2331), cystectomy was identified as an important cost driver masking potential differences between cohorts. Therefore, patients undergoing cystectomy (InQ + FU) were excluded from the adjusted study population of n = 4541 patients (WL: 79%; BL: 21%). Mean total costs of BL-TURB were initially comparable to WL-TURB (WL: EUR 4534 vs. BL: EUR 4543) and tended to be lower compared to WL-TURB in the first two quarters of FU. After one year (3rd FU quarter), costs equalized. Considering total FU, mean costs of BL-TURB were significantly lower compared to WL-TURB (WL: EUR 7073 vs BL: EUR 6431; p = 0.045).

Conclusion

This retrospective analysis of healthcare claims data highlights the comparability of costs between BL-TURB and WL-TURB.
An alternative approach for measuring yield stress and its application in Carbopol microgel
Authors: Iannotti Vincenzo , Lanotte Luca , Tomaiuolo Giovanna , Ausanio Giovanni , Graziano Raffaele , Lanotte Luciano
Published: February 2021

An innovative experimental apparatus for the direct measurement of yield stress was conceived and realized. It is based on a torsion pendulum equipped with a magnetic dipole and a rotating cylinder immersed in the material to be investigated. The pendulum equilibrium state depends on the mechanical torque applied due to an external magnetic induction field, elastic reaction of the suspension wire, and shear yield stress. Experimental results are reported showing that the behavior of the pendulum rotation angle, in different equilibrium conditions, provides evidence of the yield stress presence and enables its evaluation by equilibrium equations. The dependence on time of the equilibrium approach was also studied, contributing to shed light on the relaxation effect in the transition from a fluid-like to solid-like behavior, as well as on the eventual thixotropic effects in non-Newtonian fluids. The validity of the proposed technique and related experimental apparatus was tested in aqueous Carbopol solutions, with different weight percentages. The linear procedure, combined with the effectiveness and reliability of the proposed experimental method, candidates it to be used for the study of peculiar behaviors of other yield stress complex fluid such as blood, crude waxy oils, ice slurries, and coating layer used in the food industry and also for fault sliding in geodynamics.
Influence of high glucose in the expression of miRNAs and IGF1R signaling pathway in human myometrial explants
Authors: Favaro Rodolfo R. , Morales-Prieto Diana M. , Herrmann Jörg , Sonnemann Jürgen , Schleussner Ekkehard , Markert Udo R. , Zorn Telma M. T.
Published: February 2021

Purpose

Several roles are attributed to the myometrium including sperm and embryo transport, menstrual discharge, control of uterine blood flow, and labor. Although being a target of diabetes complications, the influence of high glucose on this compartment has been poorly investigated. Both miRNAs and IGF1R are associated with diabetic complications in different tissues. Herein, we examined the effects of high glucose on the expression of miRNAs and IGF1R signaling pathway in the human myometrium.

Methods

Human myometrial explants were cultivated for 48 h under either high or low glucose conditions. Thereafter, the conditioned medium was collected for biochemical analyses and the myometrial samples were processed for histological examination as well as miRNA and mRNA expression profiling by qPCR.

Results

Myometrial structure and morphology were well preserved after 48 h of cultivation in both high and low glucose conditions. Levels of lactate, creatinine, LDH and estrogen in the supernatant were similar between groups. An explorative screening by qPCR arrays revealed that 6 out of 754 investigated miRNAs were differentially expressed in the high glucose group. Data validation by single qPCR assays confirmed diminished expression of miR-215-5p and miR-296-5p, and also revealed reduced miR-497-3p levels. Accordingly, mRNA levels of IGF1R and its downstream mediators FOXO3 and PDCD4, which are potentially targeted by miR-497-3p, were elevated under high glucose conditions. In contrast, mRNA expression of IGF1, PTEN, and GLUT1 was unchanged.

Conclusions

The human myometrium responds to short-term exposure (48 h) to high glucose concentrations by regulating the expression of miRNAs, IGF1R and its downstream targets.
Nets of Lines with the Combinatorics of the Square Grid and with Touching Inscribed Conics
Authors: Bobenko Alexander I. , Fairley Alexander Y.
Published: February 2021

In the projective plane, we consider congruences of straight lines with the combinatorics of the square grid and with all elementary quadrilaterals possessing touching inscribed conics. The inscribed conics of two combinatorially neighbouring quadrilaterals have the same touching point on their common edge-line. We suggest that these nets are a natural projective generalisation of incircular nets. It is shown that these nets are planar Koenigs nets. Moreover, we show that general Koenigs nets are characterised by the existence of a 1-parameter family of touching inscribed conics. It is shown that the lines of any grid of quadrilaterals with touching inscribed conics are tangent to a common conic. These grids can be constructed via polygonal chains that are inscribed in conics. The special case of billiards in conics corresponds to incircular nets.
Impact of local atmospheric circulation and sea surface temperature of the East Sea (Sea of Japan) on heat waves over the Korean Peninsula
Authors: Wie Jieun , Moon Byung-Kwon , Hyun Yu-Kyung , Lee Johan
Published: February 2021

South Korea has frequently suffered from heat waves, which are mainly attributable to anomalously prolonged high-pressure systems. There have been many studies regarding the role of large-scale circulation in the Korean Peninsula heatwaves, but the contribution of local-scale circulation and sea surface temperature has not been analyzed. This study investigates the impact of local circulation and sea surface temperature (SST) of the East Sea (Sea of Japan) on the surface temperature variations of the Korean Peninsula. Based on empirical orthogonal function (EOF) analysis of the detrended daily surface temperature anomalies from July to August, 1991–2020, high-temperature days were classified into three categories: high pressure (HP), easterly wind (EW), and both high pressure and easterly wind (HPEW). On EW days, the mean surface temperatures in the western part of the peninsula are 1.75 °C higher than those on the eastern part of the windward side, indicating foehn wind warming on the leeward side. Under the synergistic effects of foehn wind warming and high-pressure anomalies, the surface temperature is the highest on HPEW days. Regression analysis also shows that, when the SST of the East Sea increased by 1 °C, the surface temperatures in the western region on HPEW and EW days increased by 0.36 °C and 0.22 °C, respectively. In contrast, the SST effect in the western region is negligible on HP days owing to the lack of foehn wind warming. Sensitivity experiments using the high-resolution Weather Research and Forecasting (WRF) model also showed that foehn wind warming becomes stronger on EW and HPEW days with warmer East Sea SST. Our results suggest that local circulation and SST are important factors in high-temperature events in the Korean Peninsula.
Group bargaining in supply chains
Authors: Clark Derek J. , Pereau Jean-Christophe
Published: February 2021

We consider a vertical supply chain in which a monopoly retailer produces a good by assembling a number of essential components each of which is owned by a monopoly. Rather than making the common assumption that the component price is set in the same way for each owner, we investigate the possibility that the retailer may profit by bargaining with some owners in a group, whilst others set their component price to maximize own profit. Furthermore, component owners can self-select into one of these groups, and the retailer can affect group formation by adjusting the order of negotiations. We present conditions under which the retailer can encourage the formation of a bargaining group, and thereby improve its own and industry profit.
The Roles of Epinephelus coioides miR-122 in SGIV Infection and Replication
Authors: Sun Hong-Yan , Su Yu-Ling , Li Pin-Hong , He Jia-Yang , Chen He-Jia , Wang Gang , Wang Shao-Wen , Huang Xiao-Hong , Huang You-Hua , Qin Qi-Wei
Published: February 2021

In mammals, mature miR-122 is 22 nucleotides long and can be involved in regulating a variety of physiological and biological pathways. In this study, the expression profile and effects of grouper Epinephelus coioides miR-122 response to Singapore grouper iridovirus (SGIV) infection were investigated. The sequences of mature microRNAs (miRNAs) from different organisms are highly conserved, and miR-122 from E. coioides exhibits high similarity to that from mammals and other fish. The expression of miR-122 was up-regulated during SGIV infection. Up-regulation of miR-122 could significantly enhance the cytopathic effects (CPE) induced by SGIV, the transcription levels of viral genes (MCP, VP19, LITAF and ICP18), and viral replication; reduce the expression of inflammatory factors (TNF-a, IL-6, and IL-8), and the activity of AP-1 and NF-κB, and miR-122 can bind the target gene p38α MAPK to regulate the SGIV-induced cell apoptosis and the protease activity of caspase-3. The results indicated that SGIV infection can up-regulate the expression of E. coioides miR-122, and up-regulation of miR-122 can affect the activation of inflammatory factors, the activity of AP-1 and NF-κB, and cell apoptosis to regulate viral replication and proliferation.
Safety and effectiveness of everolimus in maintenance kidney transplant patients in the real-world setting: results from a 2-year post-marketing surveillance study in Japan
Authors: Hayase Naomi , Yamada Mariko , Kaneko Shuhei , Watanabe Yoko
Published: February 2021

Background

Data on real-world use of everolimus (EVR) in Japanese maintenance kidney transplant (KTx) patients are limited. This post-marketing surveillance study was conducted to assess the safety and effectiveness of EVR, and identify factors affecting renal impairment.

Methods

Adult maintenance KTx patients were enrolled within 14 days of initiating EVR. Patient medical data were collected using electronic data capture case report forms at 6 months, 1, and 2 years after initiating EVR, or at discontinuation.

Results

All patients receiving EVR in Japan during the surveillance period were enrolled (N = 263). Mean time from transplantation to EVR initiation was 75.7 months. Decreased renal function (31.56%) was the primary reason for initiating EVR. In combination with EVR, the mean daily dose of tacrolimus and cyclosporine could be reduced to ~ 79 and ~ 64%, by 2 years, respectively. Incidences of serious adverse events and adverse drug reactions were 15.97 and 49.43%, respectively. Two-year graft survival rate was 95.82% and low in patients with baseline estimated glomerular filtration rate (eGFR; modification of diet in renal disease) < 30 mL/min/1.73 m2 (69.57%; P < 0.0001) and urinary protein/creatinine ratio (UPCR) ≥ 0.55 g/gCr (84.21%; P = 0.0206). Throughout the survey, mean eGFR values were stable (> 55 mL/min/1.73 m2). Renal impairment was influenced by patient and donor age, eGFR, and UPCR at baseline.

Conclusions

No new safety concerns for the use of EVR in adult maintenance KTx patients were identified. Early EVR initiation may be considered in these patients before renal function deterioration occurs.
The impact of digital pedagogy training on in-service teachers’ attitudes towards digital technologies
Authors: Pongsakdi Nonmanut , Kortelainen Arto , Veermans Marjaana
Published: February 2021

To prepare schools for the demands of the twenty-first century, teachers have been challenged to expand their use of digital technologies in their teaching. This study is a part of OpenDigi, which aimed to create teachers’ communities for enhancing digital pedagogy skills and the use of digital assessment tools. The aim of this study is to investigate the impact of digital pedagogy training on in-service teachers’ attitudes towards digital technologies. Self-report questionnaires were collected from 98 elementary and lower secondary school in-service teachers in southern Finland. A total of 22 in-service teachers completed both pre- and post-test. The results showed that the impact of the digital pedagogy training depended on teachers’ ICT confidence level. Teachers who had low confidence in ICT use showed an increased ICT confidence level after the programme, while teachers who already had high confidence in ICT use showed no significant changes in their confidence level. Moreover, the results indicated that the need for ICT support was lower after the training for the teachers in high confidence group, while there were no significant changes in the need for ICT support for the teachers in the low confidence group. These results suggested that the training could fulfil teachers’ needs for ICT support, particularly for the teachers in the high confidence group. The challenges teachers face in expanding the use of digital technologies in practice and their commitment to the digital culture are discussed.
2D:4D Ratio and Autism Spectrum Disorder in Brunei Darussalam
Authors: Lee Shirley H. F. , Aziz Syahiirah Abd , Hamid Mawarni , Lim Ya Chee , Koh David , Chaw Li Ling
Published: February 2021

Background

Despite the global increase in the prevalence of autism spectrum disorders (ASD), relevant research studies are lacking in Brunei Darussalam. Various studies have shown a significant association between a lowered 2D:4D ratio (ratio of second digit/index finger to the fourth digit/ring finger) and ASD, making it one of the potential phenotypic biomarkers for early detection of autism, which is important for early intervention and management.

Objective

The objective of this study is to explore the association between 2D:4D ratio and ASD in Brunei Darussalam, as a potential tool to complement early ASD diagnosis.

Methods

We conducted a case–control study comprising 28 ASD and 62 typically developing (TD) children in the case and control group, respectively (age range: 3–11 years old; median age: 6 years old). Median 2D:4D ratios were measured, compared and analysed between the two groups. Logistic regression models were used to explore potential associations between the median 2D:4D ratio and ASD in respective gender, for both left and right hands, independently.

Results

Our study shows that the median 2D:4D ratio of left hand in ASD males is significantly lower than those in TD males, after adjusting for ethnicity and age [Odds Ratio (OR) = 0.57 (95% Confidence Interval (CI): 0.31–0.96); p = 0.044]. For females, there is no association of ASD with the median left hand 2D:4D ratio [OR = 3.09 (95% CI: 0.98–19.86); p = 0.144] or the median right hand 2D:4D ratio [OR = 1.23 (95% CI: 0.42–3.88); p = 0.702]. Our study also shows a significant positive correlation and/or a reduced asymmetry between the average 2D:4D ratio of left hands and right hands in ASD males (Pearson’s correlation (r) = 0.48; 95% CI: 0.076–0.75, p = 0.023).

Conclusions

There is significant association between a lowered median 2D:4D ratio of the left hand (in males only) and ASD diagnosis. Once validated in a larger sample size, a lowered median 2D:4D ratio on the left hand may be a potential tool to complement ASD diagnosis for males in our study population. There is no association between the median 2D:4D ratio (left or right hands) and ASD in females, which could be due to the small female sample size and/or the possibility of different aetiology for ASD in females. Reduced asymmetry between the average 2D:4D ratio of left and right hands observed in ASD males only (not in ASD females) also suggests the importance of considering gender-specific biomarkers for ASD diagnosis.
The implementation of the unified transform to the nonlinear Schrödinger equation with periodic initial conditions
Authors: Deconinck B. , Fokas A. S. , Lenells J.
Published: February 2021

The unified transform method (UTM) provides a novel approach to the analysis of initial boundary value problems for linear as well as for a particular class of nonlinear partial differential equations called integrable. If the latter equations are formulated in two dimensions (either one space and one time, or two space dimensions), the UTM expresses the solution in terms of a matrix Riemann–Hilbert (RH) problem with explicit dependence on the independent variables. For nonlinear integrable evolution equations, such as the celebrated nonlinear Schrödinger (NLS) equation, the associated jump matrices are computed in terms of the initial conditions and all boundary values. The unknown boundary values are characterized in terms of the initial datum and the given boundary conditions via the analysis of the so-called global relation. In general, this analysis involves the solution of certain nonlinear equations. In certain cases, called linearizable, it is possible to bypass this nonlinear step. In these cases, the UTM solves the given initial boundary value problem with the same level of efficiency as the well-known inverse scattering transform solves the initial value problem on the infinite line. We show here that the initial boundary value problem on a finite interval with x-periodic boundary conditions (which can alternatively be viewed as the initial value problem on a circle) belongs to the linearizable class. Indeed, by employing certain transformations of the associated RH problem and by using the global relation, the relevant jump matrices can be expressed explicitly in terms of the so-called scattering data, which are computed in terms of the initial datum. Details are given for NLS, but similar considerations are valid for other well-known integrable evolution equations, including the Korteweg–de Vries (KdV) and modified KdV equations.
Predicting blood-to-plasma concentration ratios of drugs from chemical structures and volumes of distribution in humans
Authors: Mamada Hideaki , Iwamoto Kazuhiko , Nomura Yukihiro , Uesawa Yoshihiro
Published: February 2021

Despite their importance in determining the dosing regimen of drugs in the clinic, only a few studies have investigated methods for predicting blood-to-plasma concentration ratios (Rb). This study established an Rb prediction model incorporating typical human pharmacokinetics (PK) parameters. Experimental Rb values were compiled for 289 compounds, offering reliable predictions by expanding the applicability domain. Notably, it is the largest list of Rb values reported so far. Subsequently, human PK parameters calculated from plasma drug concentrations, including the volume of distribution (Vd), clearance, mean residence time, and plasma protein binding rate, as well as 2702 kinds of molecular descriptors, were used to construct quantitative structure–PK relationship models for Rb. Among the evaluated PK parameters, logVd correlated best with Rb (correlation coefficient of 0.47). Thus, in addition to molecular descriptors selected by XGBoost, logVd was employed to construct the prediction models. Among the analyzed algorithms, artificial neural networks gave the best results. Following optimization using six molecular descriptors and logVd, the model exhibited a correlation coefficient of 0.64 and a root-mean-square error of 0.205, which were superior to those previously reported for other Rb prediction methods. Since Vd values and chemical structures are known for most medications, the Rb prediction model described herein is expected to be valuable in clinical settings.

Graphical abstract
Effort investment in uncontrollable situations: The moderating role of motivation toward closure
Authors: Szwed Paulina , Kossowska Małgorzata , Bukowski Marcin
Published: February 2021

According to the principle of energy-conservation principle, effort investment is usually reduced in situations that are perceived as uncontrollable. This is because when success is recognized as impossible, any effortful actions are no longer justified. However, we predicted that individual differences in uncertainty tolerance, i.e., the need for closure (NFC), may moderate effort investment in uncontrollable situations. We tested this prediction in two experimental studies in which we exposed participants with differing levels of NFC to uncontrollable events, and indexed effort through the assessment of systolic blood pressure (SBP) responses. As predicted, in the uncontrollability (vs. controllability) condition, effort investment decreased significantly among low- but not high-NFC participants. Since gaining certainty and achieving closure is not a critical epistemic goal for low-NFC individuals, exerting extra effort to gain certainty is therefore no longer justified. On the other hand, high-NFC participants do not withhold their efforts, as they are highly motivated to obtain certainty. These results may help to account for contradictory findings in effort-investment behaviour and add substantively to the literature concerning motivation toward closure.
Serial verb constructions and the syntax-prosody interface
Authors: Tyler Matthew , Kastner Itamar
Published: February 2021

Rolle (2020) identifies an apparent morphophonological conspiracy in serial verb constructions (SVCs) in Degema. He argues that it constitutes evidence for a partly-unified postsyntactic module, in which morphology and prosody are built in parallel (by ‘Optimality-Theoretic Distributed Morphology’). We argue that the pattern Rolle identifies in Degema SVCs instead results from the simultaneous interaction of two independently-attested syntax-prosody phenomena: (1) the pressure for adjacent verbs in an SVC to form a single prosodic unit, and (2) the suppression of redundant agreement within a single prosodic word (a.k.a. ‘Kinyalolo’s Generalization’). Thus the Degema SVC conspiracy can be localized to the syntax-prosody interface, and there is no need to adopt a unified postsyntactic morphology-prosody module like Rolle’s. We offer some further conceptual critiques of his model.
KTBoost: Combined Kernel and Tree Boosting
Authors: Sigrist Fabio
Published: February 2021

We introduce a novel boosting algorithm called ‘KTBoost’ which combineskernel boosting andtree boosting. In each boosting iteration, the algorithm adds either a regression tree or reproducing kernel Hilbert space (RKHS) regression function to the ensemble of base learners. Intuitively, the idea is that discontinuous trees and continuous RKHS regression functions complement each other, and that this combination allows for better learning of functions that have parts with varying degrees of regularity such as discontinuities and smooth parts. We empirically show that KTBoost significantly outperforms both tree and kernel boosting in terms of predictive accuracy in a comparison on a wide array of data sets.
Formalisation of Bayesian concealment
Authors: Takeuti Izumi
Published: February 2021

In order to assure the concealment by cryptographic protocols, it is an effective measure to prove the concealment in a formal logical system. In the contemporary context of cryptographic protocol, the concealment has to be proved by using probability theory. There are several concepts of concealment in probability theory. One of them is Bayesian concealment. This study proposes a formal logical system to prove the Bayesian concealment of a secret sharing scheme.
Synthesis of gold, platinum, and gold-platinum alloy nanoparticle colloids with high-power megahertz-repetition-rate lasers: the importance of the beam guidance method
Authors: Waag Friedrich , Streubel René , Gökce Bilal , Barcikowski Stephan
Published: February 2021

Nanoparticles of noble metals and their alloys are of particular interest for biomedicine and catalysis applications. The method of laser ablation of bulk metals in liquids gives facile access to such particles as  high-purity colloids and is already used in industrial research. However, the method still lacks sufficient productivity for industrial implementation into series production. The use of innovative laser technology may help to further disseminate this colloid synthesis method in the near future. Ultrashort-pulsed lasers with high powers and megahertz-repetition-rates became available recently, but place high demands on the accurate optical laser pulse delivery on the target. Full lateral pulse separation is necessary to avoid a reduction of nanoparticle productivity due to pulse shielding. In this study, we compare flexible but rather slow galvanometer scanning with much faster but more expensive polygon-wheel scanning in their performance in the production of colloidal nanoparticles by laser ablation in liquid. Both beam guidance technologies are applied in the laser ablation of gold, platinum, and a gold-rich platinum alloy in micromolar saline water. We found that the dimensions of the scan pattern are crucial. A threshold pattern length exists, at which one scan technology becomes more productive than the other one. In addition, a much lower productivity was found for the ablation of gold compared to that of platinum. Alloying gold with only 10 at.% of platinum improved the productivity nearly to the level of platinum, reaching 8.3 g/h.
Are we moving toward an energy-efficient low-carbon economy? An input–output LMDI decomposition of CO$$_{2}$$ emissions for Spain and the EU28
Authors: Serrano-Puente Darío
Published: February 2021

Spain is on a path toward the decarbonization of the economy. This is mainly due to structural changes in the economy, where less energy-intensive sectors are gaining more relevance, and due to a higher use of less carbon-intensive primary energy products. This decarbonization trend is in fact more accentuated than that observed in the EU28, but there is still much to be done in order to reverse the huge increases in emissions that occurred in Spain prior to the 2007 crisis. The technical energy efficiency is improving in the Spanish economy at a higher rate than in the EU28, although all these gains are offset by the losses that the country suffers due to the inefficient use of the energy equipment. There is an installed energy infrastructure (in the energy-consumer side) in the Spanish economy that is not working at its maximum rated capacity, but which has very high fixed energy costs that reduce the observed energy efficiency and puts at risk the achievement of the emissions and energy consumption targets set by the European institutions. We arrive to these findings by developing a hybrid decomposition approach called input–output logarithmic mean Divisia index (IO-LMDI) decomposition method. With this methodological approach, we can provide an allocation diagram scheme for assigning the responsibility of primary energy requirements and carbon-dioxide emissions to the end-use sectors, including both economic and non-productive sectors. In addition, we analyze more potential influencing factors than those typically examined, we proceed in a way that reconciles energy intensity and energy efficiency metrics, and we are able to distinguish between technical and observed end-use energy efficiency taking into account potential rebound effects and other factors.
Drought increases chlorophyll content in stems of Vitis interspecific hybrids
Authors: Rustioni Laura , Bianchi Davide
Published: February 2021

Plants respond to drought stress through different physiological mechanisms. To highlight a specific adaptation strategy related to stem photosynthetic activity, woody tissue pigmentation was studied. In this work, 25 Vitis hybrids were studied in two experimental vineyards: one of them with sufficient water availability and the other showing drought stress. 1500 reflectance spectra of woody tissues were collected. Beside the spectral elaboration and interpretation, indexes for the pigment quantification were calculated. The content and the proportion in chlorophylls (a and b) in stems were significantly modified in response to water stress. Genotypes were classified based on their plasticity/elasticity and adaptive/susceptible behavior. The cluster analysis produced 4 main groups based on their average spectra and on the spectral variations between watered and stress conditions. The most interesting genotypes concerning this trait were pointed out. Nevertheless, this adaptation mechanism could also be due to an increased detoxification necessity related to other physiological disfunctions caused by water stress. A multi-parameter approach is encouraged for phenotyping of abiotic stress tolerant plant selection. In the next future, this work will support the release of new drought tolerant rootstocks for viticulture.
Optimization-driven distribution of relief materials in emergency disasters
Authors: Yan Yan , Di Xinyue , Zhang Yuanyuan
Published: February 2021

The distribution of relief materials is an important part of post-disaster emergency rescue. To meet the needs of the relief materials in the affected areas after a sudden disaster and ensure its smooth progress, an optimized dispatch model for multiple periods and multiple modes of transportation supported by the Internet of Things is established according to the characteristics of relief materials. Through the urgent production of relief materials, market procurement, and the use of inventory collection, the needs of the disaster area are met and the goal of minimizing system response time and total cost is achieved. The model is solved using CPLX software, and numerical simulation and results are analyzed using the example of the COVID-19 in Wuhan City, and the dispatching strategies are given under different disruption scenarios. The results show that the scheduling optimization method can meet the material demand of the disaster area with shorter time and lower cost compared with other methods, and can better cope with the supply interruptions that occur in post-disaster rescue.
A workflow language for research e-infrastructures
Authors: Candela Leonardo , Grossi Valerio , Manghi Paolo , Trasarti Roberto
Published: February 2021

Research e-infrastructures are “systems of systems,” patchworks of resources such as tools and services, which change over time to address the evolving needs of the scientific process. In such environments, researchers carry out their scientific process in terms of sequences of actions that mainly include invocation of web services, user interaction with web applications, user download and use of shared software libraries/tools. The resulting workflows are intended to generate new research products (articles, datasets, methods, etc.) out of existing ones. Sharing a digital and executable representation of such workflows with other scientists would enforce Open Science publishing principles of “reproducibility of science” and “transparent assessment of science.” This work presents HyWare, a language and execution platform capable of representing scientific processes in highly heterogeneous research e-infrastructures in terms of so-called hybrid workflows. Hybrid workflows can express sequences of “manually executable actions,” i.e., formal descriptions guiding users to repeat a reasoning, protocol or manual procedure, and “machine-executable actions,” i.e., encoding of the automated execution of one (or more) web services. An HyWare execution platform enables scientists to (i) create and share workflows out of a given action set (as defined by the users to match e-infrastructure needs) and (ii) execute hybrid workflows making sure input/output of the actions flow properly across manual and automated actions. The HyWare language and platform can be implemented as an extension of well-known workflow languages and platforms.
Social mobilization and polarization can create volatility in COVID-19 pandemic control
Authors: Hong Inho , Rutherford Alex , Cebrian Manuel
Published: February 2021

During the COVID-19 pandemic, political polarization has emerged as a significant threat that inhibits coordinated action of central and local institutions reducing the efficacy of non-pharmaceutical interventions (NPIs). Yet, it is not well-understood to what extent polarization can affect grass-roots, voluntary social mobilization targeted at mitigating the pandemic spread. Here, we propose a polarized mobilization model amidst the pandemic for demonstrating the differential responses to COVID-19 as mediated by the USA’s political landscape. We use a novel dataset and models from time-critical social mobilization competitions, voting records, and a high-resolution county-wise friendship network. Our simulations show that a higher degree of polarization impedes the overall spread of mobilization and leads to a highly-heterogeneous impact among states. Our hypothetical compliance campaign to mitigate COVID-19 spread predicts grass-roots mitigation strategies’ success before the dates of actual lockdowns in identically polarized states with more than three times of success rate than oppositely polarized states. Finally, we analyze the coupling of social mobilization leading to unrest and the growth of COVID-19 infections. These findings highlight social mobilization as both a collective precautionary measure and a potential threat to countermeasures, together with a warning message that the emerging polarization can be a significant hurdle of NPIs relying on coordinated action.