bluuebunny/crossref_metadata_2025 huggingface dataset:
Heterogeneous environmental regulation tools and green economy development: evidence from China
Authors: Lu Ma , Daixu Li , Peng Wang , Ruiqi Ma
Published: January 2023

The implementation of environmental regulation policy by the government is usually an effective tool to reduce local pollution emissions. The super-efficient SBM model of unexpected output was used in this study to estimate green economy development levels in 30 Chinese provinces from 2010 to 2019 and constructed a panel econometric model. It empirically tested the theoretical hypothesis and mechanism of heterogeneous environmental regulation affecting green economy development by using the least squares estimation, the instrumental variable method, spatial panel regression, the mediating effect model, and further models. The relationship between command-controlled environmental regulation and green economy development was U-shaped, whereas green economy development was not significantly influenced by market-incentive environmental regulations. Command-controlled environmental regulation affected green economy development via the progress of pollution control technology and production technology. The strengthening of command-controlled environmental regulation progressed pollution control technology as regional enterprises continually improved, while production technology was initially suppressed, then promoted. Market-incentive environmental regulation mainly affected the green economy development level through pollution control technology progress, while the mediating effect of production technology progress was insignificant. This study provides some empirical support for the verification of Porter’s win-win hypothesis and the realization of green economic transformation in emerging countries such as China.
Evaporation characteristics of ethanol droplet in different gases under force convection condition
Authors: Mazumder Numan Siddique , Lingfa Pradip , Neog Champak Kr
Published: January 2023

Ethanol is recognized as one of the finest alternative bio-fuels due to its natural characteristics. Fundamental studies on ethanol droplet evaporation process are mainly either in stagnant environment or using some semi-empirical co-relations. Here, a fully numerical model based on the first principle is solved to investigate the effects of various atmospheric gases (Ar, N2, O2 and CO2) on droplet evaporation phenomenon under force convective situation. Two-dimensional governing equations of species, momentum and energy transfer of spherical coordinate system are solved, and the simulation is validated quantitatively with the literature. Uniform convective strength (Re = 100) is maintained for all cases examined at T∞ = 500 K and P∞ = 0.1 MPa. From the simulation results, it is observed that the viscosity ratio (liquid to gas) has effect on droplet life time. The ethanol droplet life time increases in less viscous atmospheric gases. The ethanol droplet life time is shorter in Ar gas, but heat-up period, wet-bulb temperature, and the surface blowing effect are higher in Ar compared to other atmospheric gases. The heat-up periods of the ethanol droplet in Ar, CO2, N2 and O2 atmosphere occupy around 30%, 20%, 17% and 16.5% of the total life time of the droplet, respectively. It is also noticed that, the heat-up period increases with increase in the thermal conductivity ratio (liquid to gas) and vice versa. Furthermore, the flow pattern of both gas- and liquid-phase in terms of streamline and the internal temperature distributions of the droplet are visualized at various time instants.
Optimization design of spring hammer calibration device based on response surface method
Authors: Gao Jianzhuo , Luo Xin , Wang Ningxi , Chen Long
Published: January 2023

In order to improve the measurement ability of the spring hammer calibration device and reduce the energy loss in the collision process, a structural optimization design method based on response surface method is proposed. The optimization goal of this method is to minimize the deformation and mass of the impact structure. By analyzing the response surface, the influences of different size parameters on the optimization results are obtained. Optimization results show that: the relationship between the size parameters and the maximum deformation is non-linear, and the relationship with the mass is partially linear; the changes of overall length L and the upper width a have the greatest influences on the optimization results. Analysis of AONVA is carried out and the results prove the successful optimization. After optimization, the maximum deformation of impact end is 0.0085125 mm and the mass is 0.045681 kg. The maximum deformation is reduced by 24.59%, and the mass is reduced by 12.97%. The optimization meets the requirements of high strength and light weight, proving the effectiveness of the proposed design method for impact structural based on response surface curve and multi-target variable optimization. The response surface method improves the optimization efficiency while ensuring the accuracy, which is a new path for the optimization on spring hammer calibration device.
Noise-aware physics-informed machine learning for robust PDE discovery
Authors: Thanasutives Pongpisit , Morita Takashi , Numao Masayuki , Fukui Ken-ichi
Published: January 2023

This work is concerned with discovering the governing partial differential equation (PDE) of a physical system. Existing methods have demonstrated the PDE identification from finite observations but failed to maintain satisfying results against noisy data, partly owing to suboptimal estimated derivatives and found PDE coefficients. We address the issues by introducing a noise-aware physics-informed machine learning framework to discover the governing PDE from data following arbitrary distributions. We propose training a couple of neural networks, namely solver and preselector, in a multi-task learning paradigm, which yields important scores of basis candidates that constitute the hidden physical constraint. After they are jointly trained, the solver network estimates potential candidates, e.g. partial derivatives, for the sparse regression to initially unveil the most likely parsimonious PDE, decided according to information criterion. Denoising physics-informed neural networks, based on discrete Fourier transform, is proposed to deliver the optimal PDE coefficients respecting the noise-reduced variables. Extensive experiments on five canonical PDEs affirm that the proposed framework presents a robust and interpretable approach for PDE discovery, leading to a new automatic PDE selection algorithm established on minimization of the information criterion decay rate.
Nitrogen plasma passivation of GaAs nanowires resolved by temperature dependent photoluminescence
Authors: Irish Austin , Zou Xianshao , Barrigon Enrique , D’Acunto Giulio , Timm Rainer , T Borgström Magnus , Yartsev Arkady
Published: January 2023

We demonstrate a significant improvement in the optical performance of GaAs nanowires achieved using a mixed nitrogen-hydrogen plasma which passivates surface states and reduces the rate of nonradiative recombination. This has been confirmed by time-resolved photoluminescence measurements. At room temperature, the intensity and lifetime of radiative recombination in the plasma-treated nanowires was several times greater than that of the as-grown GaAs nanowires. Low-temperature measurements corroborated these findings, revealing a dramatic increase in photoluminescence by two orders of magnitude. Photoelectron spectroscopy of plasma passivated nanowires demonstrated a yearlong stability achieved through the replacement of surface oxygen with nitrogen. Furthermore, the process removed the As0 defects observed on non-passivated nanowires which are known to impair devices. The results validate plasma as a nitridation technique suitable for nanoscale GaAs crystals. As a simple ex situ procedure with modest temperature and vacuum requirements, it represents an easy method for incorporating GaAs nanostructures into optoelectronic devices.
In vitro assessment of the pulmonary toxicity of particulate matter emitted during haze events in Chiang Mai, Thailand via investigation of macrophage responses
Authors: Maciaszek Krystyna , Gillies Suzanne , Kawichai Sawaeng , Prapamontol Tippawan , Santijitpakdee Teetawat , Kliengchuay Wissanupong , Sahanavin Narut , Mueller William , Vardoulakis Sotiris , Samutrtai Pawitrabhorn , Cherrie John W , Brown David M , Tantrakarnapa Kraichat , Johnston Helinor J
Published: January 2023

Chiang Mai (Thailand) experiences severe haze pollution in the dry season (December–April) each year mainly due to local and regional biomass burning (e.g. of agricultural land). A major component of the haze is airborne particulate matter (PM). During haze events, biomass burning is likely to be the dominant source of PM emissions, and at other times emissions from traffic dominate. The hazard of traffic derived PM has been extensively investigated previously but there are uncertainties regarding the toxicity of PM emitted from biomass burning. The toxicity of PM10 samples collected during and after haze events in Chiang Mai in 2020 was compared in vitro in J774.1 macrophages as they are responsible for the clearance of inhaled particles. Diesel exhaust particles and ultrafine carbon black were included as benchmark particles as they have been commonly used as a surrogate for PM. Cytotoxicity was evaluated 24 h post exposure at concentrations of 3.9–125 µg ml−1. Cytokine production (tumour necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-1β, macrophage inflammatory protein (MIP-2)) was assessed and cell morphology visualised using light and scanning electron microscopy. The hydrodynamic diameter, zeta potential and endotoxin content of all particles was assessed as well as the metal content of PM samples. All particles induced a concentration dependent decrease in cell viability and increased TNF-α and MIP-2 production. Only PM samples stimulated IL-6 production and only non-haze PM caused IL-1β production. No change in IL-10 production was detected for any particle. PM samples and DEP caused vacuole formation in cells. The concentrations of endotoxin and metals were highest in non-haze PM, which may explain why it induced the greatest inflammatory response. As non-haze PM was more toxic than haze PM, our results indicate that the source of PM emissions can influence its toxic potency and more specifically, that PM emitted from biomass burning may be less toxic than PM emitted from traffic.
Alloimmunization Against RBC Antigens Is Not Associated With Decreased Survival in Liver Transplant Recipients
Authors: Chornenkyy Yevgen , Gama Alcino Pires , Felicelli Christopher , Khurram Nigar , Booth Adam L , Leventhal Joseph R , Ramsey Glenn Eugene , Yang Guang-Yu
Published: January 2023

Background

Improvement of liver transplantation (LT) outcomes requires better understanding of factors affecting survival. The presence of RBC alloantibodies (RBCAs) on survival in LT recipients was evaluated.

Methods

This study was a single-center, retrospective cohort study reviewing transfusion records and all-cause mortality between 2002 and 2021.

Results

Between 2002 and 2021, 2079 LTs were completed, 1,396 of which met inclusion criteria (1,305 RBCA negative; 91 RBCA positive [6.5%]). The cohorts were similar in age (mean [range], 55.8 [17-79] years vs 56.8 [25-73] years; P = .41, respectively) or sex (RBCA negative, 859 [65%] men and 446 [35%] women vs RBCA positive, 51 [56%] men and 40 [44%] women; P = .0684). Of 132 RBCAs detected, 10 were most common were to E (27.27%), Jka (15.91%), K (9.09%), C (8.33%), M (6.06%), D (5.3%), Fya (4.55%), e (2.27%), c (2.27%), and Jkb (2.27%). Twenty-seven patients (29.7%) had more than 1 RBCA; the most common combinations were C with Jka (7.4%) and E with Dia (7.4%). All-cause mortality was increased in men (men, 14.45 years vs women, 17.27 years; P = .0266) and patients 65 years of age and older (≥65 years of age, 10.21 years vs <64 years of age, 17.22 years; P < .0001). The presence of RBCA (≥1) did not affect all-cause mortality (RBCA negative, 14.17 years vs RBCA positive, 15.29 years; P = .4367). The top 5 causes of death were infection (11.9%), primary malignancy (solid) (10.8%), recurrent malignancy (10.5%), cardiovascular arrest (7.1%), and pulmonary insufficiency/respiratory failure (5.7%).

Conclusions

Survival in RBCA-positive LT recipients is no different from that in RBCA-negative LT recipients.
Multi-discourse Modes in Student Writing: Effects of Combining Narrative and Argument Discourse Modes on Argumentative Essay Scores
Authors: Wang Zhan , Chiu Ming Ming
Published: January 2023

Although many studies modelled writing quality by analysing basic skills (spelling, grammar, etc.), few focused on top-down compositional strategies at the discourse level. We propose that using both narrative and argument discourse modes in an argumentative essay (a multi-discourse mode [MDM] strategy) capitalizes on their complementary advantages, yielding higher quality argumentative essays. We tested whether MDM strategy and linguistic features were linked to essay scores in 695 Chinese high-stakes exam essays by upper secondary school students. Path analyses showed that essays with the MDM strategy had higher scores. MDM essays also featured more words, shorter sentences, more infrequent words, and more concrete words—all contributing to higher essay scores. Additionally, essays written from a picture prompt (versus a text prompt) had higher scores. This study captures how discourse strategies can improve essay writing.
Predicting protein stability changes upon mutation using a simple orientational potential
Authors: Hernández Iván Martín , Dehouck Yves , Bastolla Ugo , López-Blanco José Ramón , Chacón Pablo
Published: January 2023

Motivation

Structure-based stability prediction upon mutation is crucial for protein engineering and design, and for understanding genetic diseases or drug resistance events. For this task, we adopted a simple residue-based orientational potential that considers only three backbone atoms, previously applied in protein modeling. Its application to stability prediction only requires parametrizing 12 amino acid-dependent weights using cross-validation strategies on a curated dataset in which we tried to reduce the mutations that belong to protein–protein or protein–ligand interfaces, extreme conditions and the alanine over-representation.

Results

Our method, called KORPM, accurately predicts mutational effects on an independent benchmark dataset, whether the wild-type or mutated structure is used as starting point. Compared with state-of-the-art methods on this balanced dataset, our approach obtained the lowest root mean square error (RMSE) and the highest correlation between predicted and experimental ΔΔG measures, as well as better receiver operating characteristics and precision-recall curves. Our method is almost anti-symmetric by construction, and it performs thus similarly for the direct and reverse mutations with the corresponding wild-type and mutated structures. Despite the strong limitations of the available experimental mutation data in terms of size, variability, and heterogeneity, we show competitive results with a simple sum of energy terms, which is more efficient and less prone to overfitting.

Availability and implementation

https://github.com/chaconlab/korpm.

Supplementary information

Supplementary data are available at Bioinformatics online.
Sperm selection by the oviduct: perspectives for male fertility and assisted reproductive technologies
Authors: Soto-Heras Sandra , Sakkas Denny , Miller David J
Published: January 2023

The contribution of sperm to embryogenesis is gaining attention with up to 50% of infertility cases being attributed to a paternal factor. The traditional methods used in assisted reproductive technologies for selecting and assessing sperm quality are mainly based on motility and viability parameters. However, other sperm characteristics, including deoxyribonucleic acid integrity, have major consequences for successful live birth. In natural reproduction, sperm navigate the male and female reproductive tract to reach and fertilize the egg. During transport, sperm encounter many obstacles that dramatically reduce the number arriving at the fertilization site. In humans, the number of sperm is reduced from tens of millions in the ejaculate to hundreds in the Fallopian tube (oviduct). Whether this sperm population has higher fertilization potential is not fully understood, but several studies in animals indicate that many defective sperm do not advance to the site of fertilization. Moreover, the oviduct plays a key role in fertility by modulating sperm transport, viability, and maturation, providing sperm that are ready to fertilize at the appropriate time. Here we present evidence of sperm selection by the oviduct with emphasis on the mechanisms of selection and the sperm characteristics selected. Considering the sperm parameters that are essential for healthy embryonic development, we discuss the use of novel in vitro sperm selection methods that mimic physiological conditions. We propose that insight gained from understanding how the oviduct selects sperm can be translated to assisted reproductive technologies to yield high fertilization, embryonic development, and pregnancy rates.
HPLC-UV Method Development and Validation to Monitor Difluprednate Synthesis
Authors: Sammut Bartolo Nicolette , Vella Szijj Janis , Ferrito Victor , Serracino-Inglott Anthony
Published: January 2023

During the synthesis of active pharmaceutical ingredients (APIs) there is a need for the development and validation of a simple and rapid high performance liquid chromatography (HPLC) method for the determination and quantification of the synthesized product and related by-products. An HPLC method gives a better understanding of how a synthesis is proceeding. A rapid and easy to use HPLC-UV (ultraviolet) method for the determination of difluprednate and monitoring of impurities generated during synthesis was developed and validated. A Shimadzu VP Series HPLC equipped with a LabSolutions software and UV detector set at 240 nm was used for analysis. The mobile phase consisted of phosphate buffer (pH 6) and acetonitrile 50:50 (v/v) and was eluted at a flow rate of 1.2 mL/min. Separation took place on a reversed-phase Kinetex C18 column (150 × 4.60 mm; 5 μm i.d.). Column temperature was set at 40°C. The developed method was found to have good linearity and acceptable accuracy and precision. The developed method may be effectively applied to determine products and by-products formed during synthetic reactions of steroids and to calculate the yield of the products obtained during each step of the synthesis.
A New Approach of Evaluating the Security Against Differential and Linear Cryptanalysis and Its Applications to Serpent, NOEKEON and ASCON
Authors: Zhou Chunning , Zhang Wentao , Cao Weiwei
Published: January 2023

In recent years, Mixed-Integer Linear Programming (MILP)-based automatic tools have played a significant role in providing security evaluations of symmetric-key primitives. Differential and linear cryptanalysis are the two most important cryptographic techniques. Although some methods have conducted a great effort in exploiting MILP-aided tools in searching for differential (linear) characteristics, traditional methods still suffer from primitives with strong diffusion layers and large sizes, such as NOEKEON. Typically, searching for differential (linear) characteristics of such primitives is difficult, and the corresponding MILP models are too heavy to be solved efficiently. To this end, we propose a simple yet efficient approach to employ MILP to evaluate the security against differential and linear cryptanalysis of such primitives. The core of our approach is to reduce the complex problem to a set of simpler subproblems and obtain the optimal solution of the complex problem by combining all the subproblems. A subproblem is equivalent to searching for all differential (linear) characteristics with a fixed number of active S-boxes in each round. Furthermore, we design an elaborate algorithm consisting of three MILP-aided methods to solve various subproblems and adopt some techniques to improve efficiency further. Applying our new algorithm to three SPN primitives Serpent, NOEKEON and ASCON, we obtain the tightest security bounds against differential and linear cryptanalysis for all three primitives so far and find improved differential and linear characteristics for Serpent and NOEKEON. For Serpent, we improve the upper bound of the maximum probability of 7-round differential characteristics from $2^{-71}$ to $2^{-76}$ and find for the first time 7-round differential characteristics. For NOEKEON, our results show that there is no 9-round (10-round) differential (linear) characteristic with a probability (correlation) higher than $2^{-128}$ ($2^{-64}$), whereas it needs 10 rounds (11 rounds) according to the previous results. In addition, we find an 8-round (9-round) differential (linear) characteristic with a probability (correlation) of $2^{-127}$ ($2^{-60}$). For ASCON permutation, we provide for the first time an upper bound of the maximum probability (correlation) of 5-round differential (linear) characteristics as $2^{-70}$ ($2^{-33}$).
Coronary-subclavian steal syndrome: a case report of a rare entity that can become a deadly threat
Authors: Monteagudo-Vela María , Bastante Teresa , Monguió-Santín Emilio , del Val David , Panoulas Vasileios , Reyes-Copa Guillermo
Published: January 2023

Background

In patients who underwent coronary artery bypass graft (CABG), the coronary-subclavian steal syndrome (CSSS) is characterized by a subclavian artery stenosis proximal to the origin of the internal mammary artery resulting in functional graft failure.

Case summary

A 62-year-old gentleman underwent CABG following a non-ST elevation myocardial infarction and an angiogram showing left main stem and three-vessel disease. Forty-eight hours later he developed cardiogenic shock that improved with inotropic support and intra-aortic balloon pump insertion. However, 7 days later, he deteriorated again and even though the myocardial injury markers and echocardiogram were normal, an angiography was performed showing significant CSSS. Due to the chronic nature of his subclavian stenosis and the severity of the cardiogenic shock, the heart team decided to treated his epicardial disease percutaneously and occlude the left internal mammary artery in its mid-segment with coils. The patient was discharged home 28 days after CABG and has remained since asymptomatic with improvement in his functional class.

Discussion

Coronary-subclavian steal syndrome is a rare but fatal complication with increased morbidity and mortality due to reduced awareness amongst medical professionals. Subclavian artery stenosis stenting is the gold standard treatment; herein we present a new approach for complex and very sick patients in whom it is not possible to open the subclavian artery percutaneously. Increased awareness and prompt diagnosis of this pathology in CABG patients are essential for successful outcomes.
Multivessel coronary spasm triggered by ganglionated plexi stimulation during atrial fibrillation radiofrequency catheter ablation: a case report
Authors: De Innocentiis Carlo , Astore Pasquale , Giannantonio Maria , Ienco Vincenzo , Santamaria Matteo
Published: January 2023

Background

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in adults, and it is associated with a high burden of mortality and morbidity worldwide. AF can be managed with rate-control or rhythm-control strategies. The latter is increasingly used to improve symptoms and prognosis in selected patients, especially after the development of catheter ablation. Although this technique is generally considered safe, it is not free from rare but life-threatening procedure-related adverse events. Among these, coronary artery spasm (CAS) is an uncommon but potentially fatal complication that requires immediate diagnosis and treatment.

Case summary

We report a case of severe multivessel CAS triggered by ganglionated plexi stimulation during pulmonary vein isolation with radiofrequency catheter ablation in a patient with persistent AF, promptly resolved after intracoronary nitrate administration.

Discussion

Although rare, CAS is a serious complication of AF catheter ablation. Immediate invasive coronary angiography is key for both diagnosis confirmation and treatment of such dangerous condition. As the number of invasive procedures increases, it is important that both interventional and general cardiologists are aware of possible procedure-related adverse events.
Percutaneous closure of giant aneurysmal coronary artery-to-coronary sinus fistulae with guidance from three-dimensional printed models: a case series
Authors: Kanduri Jaya , Truong Quynh A , Shin James , Wong Shing-Chiu , Bergman Geoffrey , Kim Luke , Holzer Ralf , Singh Harsimran S
Published: January 2023

Background

Coronary artery fistulae are abnormal communications of coronary arteries with systemic vasculature, pulmonary vasculature, or cardiac chambers. Use of multimodality imaging can be paramount to understanding anatomical and functional features of these complex vascular lesions, therefore optimizing success of potential curative interventions.

Case summary

We present two patients with incidentally discovered giant aneurysmal coronary arteries with distal fistulous connections to the coronary sinus, which were successfully closed percutaneously with Amplatzer Septal Occluders using the assistance of three-dimensional (3D) printed heart models.

Conclusion

Computed tomography–guided reconstruction with 3D multiplanar, multicolour printed models can help augment visuospatial understanding of the size, origin, course, and drainage of giant aneurysmal coronary artery-to-coronary sinus fistulae, and with manual bench testing can assist with choosing accurately sized and shaped devices for closure.
Target therapy forBRAFmutated anaplastic thyroid cancer: a clinical and molecular study
Authors: da Silva Tiago Nunes , Rodrigues Ricardo , Saramago Ana , Pires Carolina , Rito Miguel , Horta Mariana , Martins Carmo , Leite Valeriano , Cavaco Branca M
Published: January 2023

Objectives

Anaplastic thyroid carcinoma (ATC) has a poor survival. The combination of Dabrafenib plus Trametinib (DT) had a significant impact in survival of BRAF p.V600E patients. However, durable responses may be compromised by resistance. We aim to present our experience with DT in BRAF positive ATC patients and compare the outcomes with usual therapy, and to study tumor molecular alterations in the DT group.

Methods

Patients treated between May 2018 and April 2022 in a tertiary referral center, assessed for BRAF status were included. Patients were divided in three groups: BRAF p.V600E treated with DT, BRAF wild type (WT) under multimodal therapy (MT), and BRAF WT under compassionate care (CC). Response was assessed monthly in the first 6 months and every 3 months afterwards, by RECIST 1.1. Overall survival (OS) and progression-free survival (PFS) were estimated with the Kaplan-Meier method and compared with the log-rank test.

Results

Twenty-seven ATC patients were included (DT = 9, MT = 8, and CC = 10). Median OS was 475 days for DT, 156 days for MT, and 39 days for CC (P < .001). At 12 months, only patients in the DT group were alive (71%). Median PFS was 270 days, in the DT group, compared with less than 32 days in BRAF WT (P < .001). No severe adverse events were reported. Molecular profiling showed that in one of the four clinical progressions, a pathogenic NRAS mutation was found.

Conclusions

Our results show a significant real-world efficacy of Dabrafenib plus Trametinib in both survival and recurrence compared with standard treatment, with a good safety profile.
The naturally occurring GIP(1-30)NH2 is a GIP receptor agonist in humans
Authors: Krogh Liva S L , Henriksen Kristine , Stensen Signe , Skov-Jeppesen Kirsa , Bergmann Natasha C , Størling Joachim , Rosenkilde Mette M , Hartmann Bolette , Holst Jens J , Gasbjerg Lærke S , Knop Filip K
Published: January 2023

Objective

The gut hormone glucose-dependent insulinotropic polypeptide (GIP) is an important regulator of glucose and bone metabolism. In rodents, the naturally occurring GIP variant, GIP(1-30)NH2, has shown similar effects as full-length GIP (GIP(1-42)), but its effects in humans are unsettled. Here, we investigated the actions of GIP(1-30)NH2 compared to GIP(1-42) on glucose and bone metabolism in healthy men and in isolated human pancreatic islets.

Methods

Nine healthy men completed three separate three-step glucose clamps (0-60 minutes at fasting plasma glucose (FPG) level, 60-120 minutes at 1.5× FPG, and 120-180 minutes at 2× FPG) with infusion of GIP(1-42) (4 pmol/kg/min), GIP(1-30)NH2 (4 pmol/kg/min), and saline (9 mg/mL) in randomised order. Blood was sampled for measurement of relevant hormones and bone turnover markers. Human islets were incubated with low (2 mmol/L) or high (20 mmol/L) d-glucose with or without GIP(1-42) or GIP(1-30)NH2 in three different concentrations for 30 minutes, and secreted insulin and glucagon were measured.

Results

Plasma glucose (PG) levels at FPG, 1.5× FPG, and 2× FPG were obtained by infusion of 1.45 g/kg, 0.97 g/kg, and 0.6 g/kg of glucose during GIP(1-42), GIP(1-30)NH2, and saline, respectively (P = .18), and were similar on the three experimental days. Compared to placebo, GIP(1-30)NH2 resulted in similar glucagonotropic, insulinotropic, and carboxy-terminal type 1 collagen crosslinks-suppressing effects as GIP(1-42). In vitro experiments on human islets showed similar insulinotropic and glucagonotropic effects of the two GIP variants.

Conclusions

GIP(1-30)NH2 has similar effects on glucose and bone metabolism in healthy individuals and in human islets in vitro as GIP(1-42).
Lack of sensitivity of diagnostic Cushing-scores in Germany: a multicenter validation
Authors: Braun Leah T , Vogel Frederick , Rubinstein German , Zopp Stephanie , Nowak Elisabeth , Constantinescu Georgiana , Masjkur Jimmy , Detomas Mario , Pamporaki Christina , Altieri Barbara , Deutschbein Timo , Quinkler Marcus , Beuschlein Felix , Reincke Martin
Published: January 2023

Objective

Endogenous Cushing's syndrome (CS) is a severe condition, often diagnosed at a late stage. To reduce mortality, early diagnosis plays an important role. Two screening tools for early identification of patients with CS have been developed in multicentric cohorts, but have not yet been validated in cohorts with different geographic backgrounds.

Design

We validated the Spanish score published by Leon-Justel et al. in 2016 and the Italian score by Parasiliti-Caprino et al. published in 2021 in our cohort.

Methods

In the multicentric German Cushing registry, patients with confirmed and expected but ruled out Cushing's syndrome are prospectively diagnosed and followed up. We validated both scores in a cohort of 458 subjects: 176 patients with confirmed CS and 282 patients with suspected, but finally excluded CS.

Results

Using the Spanish score, 17.5% of our patients with proven CS biochemical screening would not have been recommended. This concerned patients with pituitary CS (22%) and with adrenal CS (10%). On the contrary, only 14% of patients without CS would have received a recommendation for biochemical screening. Using the Italian score, 29% of patients with proven CS were classified into the low-risk classes not recommended for biochemical screening. This mostly affected patients with adrenal (31%) and pituitary CS (30%). About 12% of subjects without CS would have received a biochemical screening recommendation.

Conclusions

Both scores had limited sensitivity and high specificity in a German validation cohort. Further research is necessary to develop a screening score, which is effective in different healthcare systems and ethnicities.
Classic and 11-oxygenated androgens in serum and saliva across adulthood: a cross-sectional study analyzing the impact of age, body mass index, and diurnal and menstrual cycle variation
Authors: Schiffer Lina , Kempegowda Punith , Sitch Alice J , Adaway Joanne E , Shaheen Fozia , Ebbehoj Andreas , Singh Sumitabh , McTaggart Malcom P , O’Reilly Michael W , Prete Alessandro , Hawley James M , Keevil Brian G , Bancos Irina , Taylor Angela E , Arlt Wiebke
Published: January 2023

Objective

11-oxygenated androgens significantly contribute to the circulating androgen pool. Understanding the physiological variation of 11-oxygenated androgens and their determinants is essential for clinical interpretation, for example, in androgen excess conditions. We quantified classic and 11-oxygenated androgens in serum and saliva across the adult age and body mass index (BMI) range, also analyzing diurnal and menstrual cycle-dependent variation.

Design

Cross-sectional. Morning serum samples were collected from 290 healthy volunteers (125 men, 22-95 years; 165 women, 21-91 years). Morning saliva samples were collected by a sub-group (51 women and 32 men). Diurnal saliva profiles were collected by 13 men. Twelve women collected diurnal saliva profiles and morning saliva samples on 7 consecutive days during both follicular and luteal menstrual cycle phases.

Methods

Serum and salivary steroids were quantified by liquid chromatography–tandem mass spectrometry profiling assays.

Results

Serum classic androgens decreased with age-adjusted BMI, for example, %change kg/m2 for 5α-dihydrotestosterone: men −5.54% (95% confidence interval (CI) −8.10 to −2.98) and women −1.62% (95%CI −3.16 to −0.08). By contrast, 11-oxygenated androgens increased with BMI, for example, %change kg/m2 for 11-ketotestosterone: men 3.05% (95%CI 0.08-6.03) and women 1.68% (95%CI −0.44 to 3.79). Conversely, classic androgens decreased with age in both men and women, while 11-oxygenated androgens did not. Salivary androgens showed a diurnal pattern in men and in the follicular phase in women; in the luteal phase, only 11-oxygenated androgens showed diurnal variation.

Conclusions

Classic androgens decrease while active 11-oxygenated androgens increase with increasing BMI, pointing toward the importance of adipose tissue mass for the activation of 11-oxygenated androgens. Classic but not 11-oxygenated androgens decline with age.
Identifying strengths and weaknesses of methods for computational network inference from single-cell RNA-seq data
Authors: McCalla Sunnie Grace , Fotuhi Siahpirani Alireza , Li Jiaxin , Pyne Saptarshi , Stone Matthew , Periyasamy Viswesh , Shin Junha , Roy Sushmita
Published: January 2023

Single-cell RNA-sequencing (scRNA-seq) offers unparalleled insight into the transcriptional programs of different cellular states by measuring the transcriptome of thousands of individual cells. An emerging problem in the analysis of scRNA-seq is the inference of transcriptional gene regulatory networks and a number of methods with different learning frameworks have been developed to address this problem. Here, we present an expanded benchmarking study of eleven recent network inference methods on seven published scRNA-seq datasets in human, mouse, and yeast considering different types of gold standard networks and evaluation metrics. We evaluate methods based on their computing requirements as well as on their ability to recover the network structure. We find that, while most methods have a modest recovery of experimentally derived interactions based on global metrics such as Area Under the Precision Recall curve, methods are able to capture targets of regulators that are relevant to the system under study. Among the top performing methods that use only expression were SCENIC, PIDC, MERLIN or Correlation. Addition of prior biological knowledge and the estimation of transcription factor activities resulted in the best overall performance with the Inferelator and MERLIN methods that use prior knowledge outperforming methods that use expression alone. We found that imputation for network inference did not improve network inference accuracy and could be detrimental. Comparisons of inferred networks for comparable bulk conditions showed that the networks inferred from scRNA-seq datasets are often better or at par with the networks inferred from bulk datasets. Our analysis should be beneficial in selecting methods for network inference. At the same time, this highlights the need for improved methods and better gold standards for regulatory network inference from scRNAseq datasets.
Third-space endoscopy: the final frontier
Authors: Hayat Maham , Yang Dennis , Draganov Peter V
Published: January 2023

Over the years, our growing experience with endoscopic submucosal dissection along with technological advances has solidified our comfort and knowledge on working in the submucosa, also referred to as the “third space.” Per-oral endoscopic myotomy (POEM) was the first prototype third-space endoscopy (TSE) procedure, demonstrating the feasibility and clinical utility of endoscopic esophagogastric myotomy via submucosal tunneling. The launch of POEM accelerated the evolution of TSE from a vanguard concept to an expanding field with a wide range of clinical applications. In this review, we discuss the status and future directions of multiple TSE interventions.
Decrease in Gait Speed Over Time Is Associated With Increase in Number of Depression Symptoms in Older Adults With Type 2 Diabetes
Authors: Lavie Inbar , Schnaider Beeri Michal , Schwartz Yonathan , Soleimani Laili , Heymann Anthony , Azuri Joseph , Ravona-Springer Ramit
Published: January 2023

Background

We examined the cross-sectional and longitudinal relationships of motor functions with depression in older adults with type 2 diabetes (T2D).

Methods

Participants (n = 984) were from the longitudinal Israel Diabetes and Cognitive Decline (IDCD) study. They were initially cognitively normal and underwent evaluations of motor functions (grip strength and gait speed) and of depression (using the 15-item version of the Geriatric Depression Scale [GDS]) approximately every 18 months. We applied Hierarchical Linear Mixed Models (HLMM) to investigate the associations between motor functions and depression adjusting for sociodemographic, cardiovascular factors, overall cognitive score, and subjective report of exhaustion.

Results

Participants’ baseline characteristics were 72 (±5) years of age (59.6% males), 13 (±4) years of education, Mini-Mental Status Exam (MMSE) score of 28.01 (±1.78), and a GDS score of (2 ± 2.00), consistent with normal cognitive status and lack of major affective symptomatology. Slower gait speed at baseline was associated with higher GDS scores (p = .001) and with their increase over time (p = .049). A decrease in walking speed from baseline was associated with an increase in GDS scores (p = .015). Lower grip strength at baseline was associated with higher GDS scores (p = .002), but not with trajectories in GDS scores over time. A faster decrease in grip strength from baseline was associated with a faster increase in GDS scores (p = .022).

Conclusions

Both gait speed and grip strength are cross-sectionally associated with depression. However, only gait speed and its decrease over time can potentially be used to predict incident depression symptoms, thus facilitating the introduction of depression prevention strategies.
Different Sources of Sugar Consumption and Cognitive Performance in Older Adults: Data From the National Health and Nutrition Examination Survey 2011–2014
Authors: Gomes Gonçalves Natalia , Suemoto Claudia Kimie , Ferreira Naomi Vidal
Published: January 2023

Objectives

Excess sugar consumption, particularly in sugar-sweetened beverages (SSBs), has been linked to poor cognitive performance. We aimed to assess the association of consumption of total sugar, as well as the consumption of SSBs, solid desserts, and 100% fruit juice with cognitive performance among older adults.

Methods

Consumption of total sugar, SSBs, solid desserts, and 100% fruit juice were obtained from the 24-hr recall interview. Cognitive performance was evaluated using the Consortium to Establish a Registry for Alzheimer’s Disease word list, the Animal Fluency Test, and the Digit Symbol Substitution Test. Binary logistic regression models were used to evaluate the association between consumption of sugar (total and from different sources) and cognitive performance.

Results

A total of 1,938 participants aged 60 years or older from the National Health and Nutrition Examination Survey 2011–2014 were included. Compared to the lowest tertile, the highest tertile of total sugar consumption was independently associated with higher odds of low memory performance (odds ratio [OR] = 1.87, 95% confidence interval [CI] = 1.00; 3.50, p = .049). Consumption of SSBs was associated with higher risk of low memory (OR = 1.58, 95% CI = 1.11; 2.25, p = .014), whereas consumption of solid desserts was associated with lower risk of low verbal fluency performance (OR = 0.62, 95% CI = 0.41; 0.95, p = .032).

Discussion

Higher consumption of total sugars and SSBs was associated with lower memory performance, while consumption of solid desserts was associated with higher verbal fluency performance.
Reciprocal Relationship Between Lifelong Learning and Volunteering Among Older Adults
Authors: Sung Pildoo , Chia Arthur , Chan Angelique , Malhotra Rahul
Published: January 2023

Objectives

Lifelong learning and volunteering contribute to not only health and well-being, but also social inclusion and cohesion among older adults. However, less is known about whether lifelong learning and volunteering promote each other. This study examined the reciprocal relationship between older adults’ lifelong learning and volunteering and whether the relationship varied by the purpose of lifelong learning.

Methods

Cross-lagged panel models were applied to data on 2,608 older adults, aged 60 years and older, from 2 waves of a national longitudinal study from Singapore.

Results

We found a bidirectional relationship between lifelong learning and volunteering. However, when job-related and nonjob-related lifelong learning were considered separately, only nonjob-related lifelong learning predicted volunteering. On the other hand, volunteering predicted both job-related and nonjob-related lifelong learning.

Discussion

Lifelong learning leads to volunteering, and vice versa, creating a virtuous circle of productive social engagement in later life. Programs or initiatives engaging older adults in either productive activity should promote and provide opportunities for participation in the other activity.
The viscoacoustic Green's function for the Helmholtz equation in a velocity gradient interface model
Authors: Amundsen Lasse , Ursin Bjørn
Published: January 2023

In viscoacoustically stratified media where the density is constant, 3-D wave propagation in the frequency–radial wavenumber domain is governed by the Helmholtz equation. In the case that the model is a velocity gradient interface where the squared velocity in depth is represented by a smooth Heaviside function of the Fermi–Dirac distribution type, the Helmholtz equation for a point source at arbitrary location is shown to have analytical solution for the Green's function. The velocity depth profile, which is a modification of the Epstein profile which has been thoroughly studied in different branches of physics, is described by four parameters: the velocities at minus and plus infinity, the reference depth of the gradient interface, and its smoothness. The Helmholtz equation is first solved in a model where the point source is absent. The solution to the source-free equation has four unknown constants that must be determined. The radiation conditions at minus and plus infinity and two conditions on the Green's function at the source depth allow the constants to be found. The Green's function solution can be represented in two mathematically equivalent algebraic forms involving ordinary hypergeometric functions. The first form allows a numerically stable implementation over all wavenumber components. The second form allows a physical, intuitive interpretation and is expressed mathematically as the sum of two terms. Each of the terms contains the product of constant-velocity reference phase shift functions and hypergeometric functions which take the role to adjust the amplitude and phase shift calculated by the reference phase shift functions to account for the depth varying velocity profile. Inverse Fourier transforms take the Green's function from the frequency–wavenumber domain to the frequency–space domain or time–space domain. The Green's function solution is valid for any sharpness of the interface. Selected numerical results are presented for the 1-D and 2-D Helmholtz equation to demonstrate the influence of the velocity gradient zone on the wavefield. The 1-D solution in an acoustic model is compared in time domain to the classical finite-difference wave propagation solution. For the purpose of interpretation of seismograms, we model for comparison the wavefield response in a model of two half-spaces in welded contact. For brevity, the latter model is referenced as the HS model.
Real-World Evidence of Effectiveness and Safety of Vedolizumab for Inflammatory Bowel Disease in Taiwan: A Prospective Nationwide Registry (VIOLET) Study
Authors: Lin Wei-Chen , Tai Wei-Chen , Chang Chung-Hsin , Tu Chia-Hung , Feng I-Che , Shieh Ming-Jium , Chung Chen-Shuan , Yen Hsu-Heng , Chou Jen-Wei , Wong Jau-Min , Liu Yu-Hwa , Huang Tien-Yu , Chuang Chiao-Hsiung , Tsai Tzung-Jiun , Chiang Feng-Fan , Lu Chien-Yu , Hsu Wen-Hung , Yu Fang-Jung , Chao Te-Hsin , Wu Deng-Chyang , Ho Ai-Sheng , Lin Hung-Hsin , Feng Chun-Lung , Wu Keng-Liang , Wong Ming-Wun , Tung Chien-Chih , Lin Chun-Chi , Chen Chia-Chang , Hu Huang-Ming , Lu Lung-Sheng , Wang Huann-Sheng , Wu I-Chen , Kuo Hsin-Yu , Wu Jia-Feng , Yao Shih Hsiang , Ni Yen-Hsuan , Tang Shu-Lun , Chen Peng-Hsu , Wei Shu-Chen
Published: January 2023

Background

This nationwide prospective registry study investigated the real-world effectiveness, safety, and persistence of vedolizumab (VDZ) in inflammatory bowel disease (IBD) patients in Taiwan. Disease relapse rates after VDZ discontinuation due to reimbursement restriction were assessed.

Methods

Data were collected prospectively (January 2018 to May 2020) from the Taiwan Society of IBD registry.

Results

Overall, 274 patients (147 ulcerative colitis [UC] patients, 127 Crohn’s disease [CD] patients) were included. Among them, 70.7% with UC and 50.4% with CD were biologic-naïve. At 1 year, 76.0%, 58.0%, 35.0%, and 62.2% of UC patients and 57.1%, 71.4%, 33.3%, and 30.0% of CD patients achieved clinical response, clinical remission, steroid-free remission, and mucosal healing, respectively. All patients underwent hepatitis B and tuberculosis screening before initiating biologics, and prophylaxis was recommended when necessary. One hepatitis B carrier, without antiviral prophylaxis due to economic barriers, had hepatitis B reactivation during steroid tapering and increasing azathioprine dosage, which was controlled with an antiviral agent. No tuberculosis reactivation was noted. At 12 months, non–reimbursement-related treatment persistence rates were 94.0% and 82.5% in UC and CD patients, respectively. Moreover, 75.3% of IBD patients discontinued VDZ due to mandatory drug holiday. Relapse rates after VDZ discontinuation at 6 and 12 months were 36.7% and 64.3% in CD patients and 42.9% and 52.4% in UC patients, respectively.

Conclusions

The findings demonstrated VDZ effectiveness in IBD patients in Taiwan, with high treatment persistence rates and favorable safety profiles. A substantial IBD relapse rate was observed in patients who had mandatory drug holiday.