bluuebunny/crossref_metadata_2025 huggingface dataset:
Bioinformatics methods for identification of amyloidogenic peptides show robustness to misannotated training data
Authors: Szulc Natalia , Burdukiewicz Michał , Gąsior-Głogowska Marlena , Wojciechowski Jakub W. , Chilimoniuk Jarosław , Mackiewicz Paweł , Šneideris Tomas , Smirnovas Vytautas , Kotulska Malgorzata
Published: April 2021

Several disorders are related to amyloid aggregation of proteins, for example Alzheimer’s or Parkinson’s diseases. Amyloid proteins form fibrils of aggregated beta structures. This is preceded by formation of oligomers—the most cytotoxic species. Determining amyloidogenicity is tedious and costly. The most reliable identification of amyloids is obtained with high resolution microscopies, such as electron microscopy or atomic force microscopy (AFM). More frequently, less expensive and faster methods are used, especially infrared (IR) spectroscopy or Thioflavin T staining. Different experimental methods are not always concurrent, especially when amyloid peptides do not readily form fibrils but oligomers. This may lead to peptide misclassification and mislabeling. Several bioinformatics methods have been proposed for in-silico identification of amyloids, many of them based on machine learning. The effectiveness of these methods heavily depends on accurate annotation of the reference training data obtained from in-vitro experiments. We study how robust are bioinformatics methods to weak supervision, encountering imperfect training data. AmyloGram and three other amyloid predictors were applied. The results proved that a certain degree of misannotation in the reference data can be eliminated by the bioinformatics tools, even if they belonged to their training set. The computational results are supported by new experiments with IR and AFM methods.
The TELE-DD project on treatment nonadherence in the population with type 2 diabetes and comorbid depression
Authors: Roy Juan Francisco , Lozano del Hoyo María Luisa , Urcola-Pardo Fernando , Monreal-Bartolomé Alicia , Gracia Ruiz Diana Cecilia , Gómez Borao María Mercedes , Artigas Alcázar Ana Belén , Martínez Casbas José Pedro , Aceituno Casas Alexandra , Andaluz Funcia María Teresa , García-Campayo Javier , Fernández Rodrigo María Teresa
Published: April 2021

Diabetic patients have increased depression rates, diminished quality of life, and higher death rates due to depression comorbidity or diabetes complications. Treatment adherence (TA) and the maintenance of an adequate and competent self-care are crucial factors to reach optimal glycaemic control and stable quality of life in these patients. In this report, we present the baseline population analyses in phase I of the TELE-DD project, a three-phased population-based study in 23 Health Centres from the Aragonian Health Service Sector II in Zaragoza, Spain. The objectives of the present report are: (1) to determine the point prevalence of T2D and clinical depression comorbidity and treatment nonadherence; (2) to test if HbA1c and LDL-C, as primary DM outcomes, are related to TA in this population; and (3) to test if these DM primary outcomes are associated with TA independently of shared risk factors for DM and depression, and patients’ health behaviours. A population of 7,271 patients with type-2 diabetes and comorbid clinical depression was investigated for inclusion. Individuals with confirmed diagnoses and drug treatment for both illnesses (n = 3340) were included in the current phase I. A point prevalence of 1.9% was found for the T2D-depression comorbidity. The prevalence of patients nonadherent to treatment for these diseases was 35.4%. Multivariate analyses confirmed that lower diabetes duration, increased yearly PCS visits, HbA1c and LDL-C levels were independently related to treatment nonadherence. These findings informed the development of a telephonic monitoring platform for treatment of nonadherence for people with diabetes and comorbid depression and further trial, cost-effectiveness, and prognostic studies (phases II and III).
Stimulation of zona incerta selectively modulates pain in humans
Authors: Lu Charles W. , Harper Daniel E. , Askari Asra , Willsey Matthew S. , Vu Philip P. , Schrepf Andrew D. , Harte Steven E. , Patil Parag G.
Published: April 2021

Stimulation of zona incerta in rodent models has been shown to modulate behavioral reactions to noxious stimuli. Sensory changes observed in Parkinsonian patients with subthalamic deep brain stimulation suggest that this effect is translatable to humans. Here, we utilized the serendipitous placement of subthalamic deep brain stimulation leads in 6 + 5 Parkinsonian patients to directly investigate the effects of zona incerta stimulation on human pain perception. We found that stimulation at 20 Hz, the physiological firing frequency of zona incerta, reduces experimental heat pain by a modest but significant amount, achieving a 30% reduction in one fifth of implants. Stimulation at higher frequencies did not modulate heat pain. Modulation was selective for heat pain and was not observed for warmth perception or pressure pain. These findings provide a mechanistic explanation of sensory changes seen in subthalamic deep brain stimulation patients and identify zona incerta as a potential target for neuromodulation of pain.
Correspondence analysis, spectral clustering and graph embedding: applications to ecology and economic complexity
Authors: van Dam Alje , Dekker Mark , Morales-Castilla Ignacio , Rodríguez Miguel Á. , Wichmann David , Baudena Mara
Published: April 2021

Identifying structure underlying high-dimensional data is a common challenge across scientific disciplines. We revisit correspondence analysis (CA), a classical method revealing such structures, from a network perspective. We present the poorly-known equivalence of CA to spectral clustering and graph-embedding techniques. We point out a number of complementary interpretations of CA results, other than its traditional interpretation as an ordination technique. These interpretations relate to the structure of the underlying networks. We then discuss an empirical example drawn from ecology, where we apply CA to the global distribution of Carnivora species to show how both the clustering and ordination interpretation can be used to find gradients in clustered data. In the second empirical example, we revisit the economic complexity index as an application of correspondence analysis, and use the different interpretations of the method to shed new light on the empirical results within this literature.
Machine learning with persistent homology and chemical word embeddings improves prediction accuracy and interpretability in metal-organic frameworks
Authors: Krishnapriyan Aditi S. , Montoya Joseph , Haranczyk Maciej , Hummelshøj Jens , Morozov Dmitriy
Published: April 2021

Machine learning has emerged as a powerful approach in materials discovery. Its major challenge is selecting features that create interpretable representations of materials, useful across multiple prediction tasks. We introduce an end-to-end machine learning model that automatically generates descriptors that capture a complex representation of a material’s structure and chemistry. This approach builds on computational topology techniques (namely, persistent homology) and word embeddings from natural language processing. It automatically encapsulates geometric and chemical information directly from the material system. We demonstrate our approach on multiple nanoporous metal–organic framework datasets by predicting methane and carbon dioxide adsorption across different conditions. Our results show considerable improvement in both accuracy and transferability across targets compared to models constructed from the commonly-used, manually-curated features, consistently achieving an average 25–30% decrease in root-mean-squared-deviation and an average increase of 40–50% in R2 scores. A key advantage of our approach is interpretability: Our model identifies the pores that correlate best to adsorption at different pressures, which contributes to understanding atomic-level structure–property relationships for materials design.
Motor imagery practice benefits during arm immobilization
Authors: Debarnot Ursula , Perrault Aurore. A. , Sterpenich Virginie , Legendre Guillaume , Huber Chieko , Guillot Aymeric , Schwartz Sophie
Published: April 2021

Motor imagery (MI) is known to engage motor networks and is increasingly used as a relevant strategy in functional rehabilitation following immobilization, whereas its effects when applied during immobilization remain underexplored. Here, we hypothesized that MI practice during 11 h of arm-immobilization prevents immobilization-related changes at the sensorimotor and cortical representations of hand, as well as on sleep features. Fourteen participants were tested after a normal day (without immobilization), followed by two 11-h periods of immobilization, either with concomitant MI treatment or control tasks, one week apart. At the end of each condition, participants were tested on a hand laterality judgment task, then underwent transcranial magnetic stimulation to measure cortical excitability of the primary motor cortices (M1), followed by a night of sleep during which polysomnography data was recorded. We show that MI treatment applied during arm immobilization had beneficial effects on (1) the sensorimotor representation of hands, (2) the cortical excitability over M1 contralateral to arm-immobilization, and (3) sleep spindles over both M1s during the post-immobilization night. Furthermore, (4) the time spent in REM sleep was significantly longer, following the MI treatment. Altogether, these results support that implementing MI during immobilization may limit deleterious effects of limb disuse, at several levels of sensorimotor functioning.
The feasibility of the PAM intervention to support treatment-adherence in people with hypertension in primary care: a randomised clinical controlled trial
Authors: Kassavou Aikaterini , Mirzaei Venus , Shpendi Sonia , Brimicombe James , Chauhan Jagmohan , Bhattacharya Debi , Naughton Felix , Hardeman Wendy , Eborall Helen , Van Emmenis Miranda , De Simoni Anna , Takhar Amrit , Gupta Pankaj , Patel Prashanth , Mascolo Cecilia , Prevost Andrew Toby , Morris Stephen , Griffin Simon , McManus Richard J. , Mant Jonathan , Sutton Stephen
Published: April 2021

The PAM intervention is a behavioural intervention to support adherence to anti-hypertensive medications and therefore to lower blood pressure. This feasibility trial recruited 101 nonadherent patients (54% male, mean age 65.8 years) with hypertension and high blood pressure from nine general practices in the UK. The trial had 15.5% uptake and 7.9% attrition rate. Patients were randomly allocated to two groups: the intervention group (n = 61) received the PAM intervention as an adjunct to usual care; the control group (n = 40) received usual care only. At 3 months, biochemically validated medication adherence was improved by 20% (95% CI 3–36%) in the intervention than control, and systolic blood pressure was reduced by 9.16 mmHg (95% CI 5.69–12.64) in intervention than control. Improvements in medication adherence and reductions in blood pressure suggested potential intervention effectiveness. For a subsample of patients, improvements in medication adherence and reductions in full lipid profile (cholesterol 1.39 mmol/mol 95% CI 0.64–1.40) and in glycated haemoglobin (3.08 mmol/mol, 95% CI 0.42–5.73) favoured the intervention. A larger trial will obtain rigorous evidence about the potential clinical effectiveness and cost-effectiveness of the intervention.

Trial registration Trial date of first registration 28/01/2019. ISRCTN74504989. https://doi.org/10.1186/ISRCTN74504989.
Tracing woody-organic tsunami deposits of the 2011 Tohoku-oki event in Misawa (Japan)
Authors: Bellanova Piero , Frenken Mike , Nishimura Yuichi , Schwarzbauer Jan , Reicherter Klaus
Published: April 2021

With a minimum of three reported waves, the 2011 Tohoku-oki tsunami’s destructive force caused massive damage along the northern Japanese Aomori coast. At Misawa the coastal control area was inundated up to 550 m inland and sandy sediment remnants can be traced to c. 350 m (c. 61–63% of the maximum inundation) from the shoreline. Linking the discovery of floatable plastic objects within a woody and organic layer to our analytical data lead to the detection of a yet undocumented woody-organic tsunami deposit first appearing on top of the sandy deposit but then reaching even further inland (approx. 69–72% of the max. inundation). By this observation our understanding of the documented part of the tsunami inundation may be improved. As a consequence, sand sheets of historic and paleo-tsunamis represent minimum estimates for the coastal inundation and underestimation may be reduced by addressing the woody and organic fraction of a tsunami’s inundation.
Biofilm eradication and antifungal mechanism of action against Candida albicans of cationic dicephalic surfactants with a labile linker
Authors: Paluch Emil , Szperlik Jakub , Lamch Łukasz , Wilk Kazimiera A. , Obłąk Ewa
Published: April 2021

Our research aims to expand the knowledge on relationships between the structure of cationic dicephalic surfactants—N,N-bis[3,3_-(dimethylamine)propyl]alkylamide dihydrochlorides and N,N-bis[3,3_-(trimethylammonio)propyl]alkylamide dibromides (alkyl: n-C9H19, n-C11H23, n-C13H27, n-C15H31)—and their antifungal mechanism of action on Candida albicans. The mentioned groups of amphiphilic substances are characterized by the presence of a weak, hydrochloride cationic center readily undergoing deprotonation, as well as a stable, strong quaternary ammonium group and alkyl chains capable of strong interactions with fungal cells. Strong fungicidal properties and the role in creation and eradication of biofilm of those compounds were discussed in our earlier works, yet their mechanism of action remained unclear. It was shown that investigated surfactants induce strong oxidative stress and cause increase in cell membrane permeability without compromising its continuity, as indicated by increased potassium ion (K+) leakage. Thus experiments carried out on the investigated opportunistic pathogen indicate that the mechanism of action of the researched surfactants is different than in the case of the majority of known surfactants. Results presented in this paper significantly broaden the understanding on multifunctional cationic surfactants and their mechanism of action, as well as suggest their possible future applications as surface coating antiadhesives, fungicides and antibiofilm agents in medicine or industry.
Mathematical modeling of palatal suture pattern formation: morphological differences between sagittal and palatal sutures
Authors: Shibusawa Nobuhide , Endo Yoshie , Morimoto Naoki , Takahashi Ichiro , Miura Takashi
Published: April 2021

The median palatal suture serves as a growth center for the maxilla; inadequate growth at this site causes malocclusion and dental crowding. However, the pattern formation mechanism of palatal sutures is poorly understood compared with that of calvarial sutures such as the sagittal suture. In the present study, therefore, we compared the morphological characteristics of sagittal and palatal sutures in human bone specimens. We found that palatal suture width was narrower than sagittal suture width, and the interdigitation amplitude of the palatal suture was lower than that of the sagittal suture. These tendencies were also observed in the neonatal stage. However, such differences were not observed in other animals such as chimpanzees and mice. We also used a mathematical model to reproduce the differences between palatal and sagittal sutures. After an extensive parameter search, we found two conditions that could generate the difference in interdigitation amplitude and suture width: bone differentiation threshold $$v_c$$

v
c

and growth speed c. We discuss possible biological interpretations of the observed pattern difference and its cause.
SCD5 expression correlates with prognosis and response to neoadjuvant chemotherapy in breast cancer
Authors: Zhao Weipeng , Sun Linlin , Li Xichuan , Wang Jun , Zhu Ye , Jia Yan , Tong Zhongsheng
Published: April 2021

Neoadjuvant chemotherapy (NACT) represents a standard option for breast cancer. Unfortunately, about 55–80% of breast cancer patients do not have a favorable response to chemotherapy. Highly specific tumor biomarker that can predict the pathological response to neoadjuvant chemotherapy is lacking. Stearoyl-CoA desaturase 5 (SCD5) is an integral membrane protein of the endoplasmic reticulum that participates in lipid metabolism. Previous studies on the role of SCD5 in human cancers drew different conclusions. Therefore, the role of SCD5 in breast cancer remains unclear. Our study aims to understand its expression signature, prognosis value and correlation with pathological response to NACT in breast cancer using bioinformatics from public databases. Analysis of samples from public databases showed that SCD5 expression was down-regulated in some human cancers including breast cancer, and low expression of SCD5 was associated with more aggressive breast cancer phenotypes. Survival analysis revealed that SCD5 expression was related to prognosis in breast cancer. Integrated analysis of multiple public datasets indicated that SCD5 expression signature was associated with pathological response to NACT, particularly in TNBC. Based on functional enrichment analysis, the most affected biological functions in high SCD5-expressing breast cancer tissues were involved in negative regulation of cell cycle. Moreover, a significantly negative correlation between SCD5 expression and several cell cycle regulators was noted. Taken together, SCD5 was involved in the development and progression of breast cancer and might be a predictive biomarker for response to NACT. In conclusion, SCD5 could serve as a predictive biomarker of pathological response to NACT and play a carcinostatic role in breast cancer. These results provided us with clues to better understand SCD5 from the perspective of bioinformatics and highlighted the clinical importance of SCD5 in breast cancer, especially triple negative breast cancer (TNBC).
Assessing the use of a drought-tolerant variety as adaptation strategy for maize production under climate change in the savannas of Nigeria
Authors: Tofa Abdullahi I. , Kamara Alpha Y. , Babaji Bashir A. , Akinseye Folorunso M. , Bebeley Jenneh F.
Published: April 2021

The Decision Support System for Agricultural Technology Transfer (DSSAT) was used to quantify the impact of climate change on maize yield and the potential benefits of the use of drought-tolerant maize variety over non-drought tolerant variety in savanna ecological zones of Nigeria. Projections of maize yields were estimated for three locations representing different agro-climatic zones and soil conditions, in the mid-century (2040–2069) and end-century (2070–2099) under representative concentration pathways scenarios (RCP 4.5 and 8.5) against the baseline period (1980–2009). Relative to the baseline period, the ensemble Global Circulation Models (GCMs) predicted significant increase in minimum and maximum temperatures and seasonal rainfall across the sites. In the mid-century, ensemble GCMs predicted temperatures increase between 1.7–2.4 °C for RCP4.5 and 2.2–2.9 °C for RCP8.5. By end-century, the temperature increases between 2.2–3.0 °C under RCP4.5 and 3.9–5.0 °C under RCP8.5. Predicted seasonal rainfall increase between 1.2–7% for RCP4.5 and 0.03–10.6% for RCP8.5 in the mid-century. By end of century, rainfall is expected to increase between 2–6.7% for RCP4.5 and 3.3–20.1% for RCP8.5. The DSSAT model predictions indicated a negative impact on maize yield in all the selected sites, but the degree of the impact varies with variety and location. In the mid-century, the results showed that the yield of the non–drought tolerant maize variety, SAMMAZ-16 will decline by 13–19% under RCP4.5 and 19–28% under RCP8.5. The projection by end-century indicates a decline in yield by 18–26% under RCP4.5 and 38–47% under RCP8.5. The yield of the drought-tolerant variety is projected to decline by 9–18% for RCP4.5 and 14–25% for RCP8.5 in the mid-century and 13–23% under RCP4.5 and 32–43% under RCP8.5 by the end-century. The higher temperatures by both emission scenarios (RCP 4.5 and 8.5) were primarily shown to cause more yield losses for non-drought-tolerant variety than that of the drought-tolerant variety. There will be 1–6% less reduction in yield when drought-tolerant variety is used. However, the higher yield reductions in the range of − 13 to − 43% predicted for the drought-tolerant variety by the end of the century across the study areas highlighted the need to modify the maize breeding scheme to combine both tolerances to drought and heat stresses in the agro-ecological zones of northern Nigeria.
Testicular steroidogenesis is suppressed during experimental autoimmune encephalomyelitis in rats
Authors: Milosevic Ana , Bjelobaba Ivana , Bozic Iva D. , Lavrnja Irena , Savic Danijela , Tesovic Katarina , Jakovljevic Marija , Stojilkovic Stanko S. , Janjic Marija M.
Published: April 2021

Multiple sclerosis (MS) is an autoimmune disease that usually occurs during the reproductive years in both sexes. Many male patients with MS show lower blood testosterone levels, which was also observed in male rats during experimental autoimmune encephalomyelitis (EAE), an animal model of MS. To better understand the causes of decreased testosterone production during EAE, we investigated the expression status of genes and proteins associated with steroidogenesis in the testes. No changes in the number of interstitial cells were observed in EAE animals, but the expression of the insulin-like 3 gene was reduced at the peak of the disease, implying that the Leydig cell functional capacity was affected. Consistent with this finding, the expression of most steroidogenic enzyme genes and proteins was reduced during EAE, including StAR, CYP11A1, CYP17A1 and HSD3B. No signs of testicular inflammation were observed. Recovery of steroidogenesis was observed after injection of hCG, the placental gonadotropin, or buserelin acetate, a gonadotropin-releasing hormone analogue, at the peak of EAE. Together, our results are consistent with the hypothesis that impaired testicular steroidogenesis originates upstream of the testes and that low serum LH is the main cause of decreased testosterone levels during EAE.
Comparison of bacterial communities and antibiotic resistance genes in oxidation ditches and membrane bioreactors
Authors: Luo Lifang , Yao Junqin , Liu Weiguo , Yang Lixin , Li Hailong , Liang Ming , Ma Hui , Liu Ziteng , Chen Yinguang
Published: April 2021

Oxidation ditches (ODs) and membrane bioreactors (MBRs) are widely used in wastewater treatment plants (WWTPs) with bacteria and antibiotic resistance genes (ARGs) running through the whole system. In this study, metagenomic sequencing was used to compare the bacterial communities and ARGs in the OD and MBR systems, which received the same influent in a WWTP located in Xinjiang, China. The results showed that the removal efficiency of pollutants by the MBR process was better than that by the OD process. The composition and the relative abundance of bacteria in activated sludge were similar at the phylum and genus levels and were not affected by process type. Multidrug, fluoroquinolones and peptides were the main ARG types for the two processes, with macB being the main ARG subtype, and the relative abundance of ARG subtypes in MBR effluent was much higher than that in the OD effluent. The mobile genetic elements (MGEs) in the activated sludge were mainly transposons (tnpA) and insertion sequences (ISs; IS91). These results provide a theoretical basis for process selection and controlling the spread of ARGs.
A novel cystathionine γ-lyase inhibitor, I194496, inhibits the growth and metastasis of human TNBC via downregulating multiple signaling pathways
Authors: Liu Ya , Wang Lupeng , Zhang Xiuli , Deng Yuying , Pan Limin , Li Hui , Shi Xiaoyan , Wang Tianxiao
Published: April 2021

Triple-negative breast cancer (TNBC) is a high-risk subtype of breast cancer with high capacity for metastasis and lacking of therapeutic targets. Our previous studies indicated that cystathionine γ-lyase (CSE) may be a new target related to the recurrence or metastasis of TNBC. Downregulation of CSE could inhibit the growth and metastasis of TNBC. The purpose of this study was to investigate the activity of the novel CSE inhibitor I194496 against TNBC in vivo and in vitro. The anticancer activity of I194496 in vitro were detected by MTS, EdU, and transwell assays. Methylene blue assay was used to determine the H2S level. Western blot was performed to analyze the expression of related pathway proteins. Xenograft tumors in nude mice were used to analyze the anticancer activity of I194496 in vivo. I194496 exerted potent inhibitory effects than l-propargylglycine (PAG, an existing CSE inhibitor) on human TNBC cells and possessed lower toxicity in normal breast epithelial Hs578Bst cells. I194496 reduced the activity and expression of CSE protein and the release of H2S in human TNBC cells. Meanwhile, the protein levels of PI3K, Akt, phospho (p)-Akt, Ras, Raf, p-ERK, p-Anxa2, STAT3, p-STAT3, VEGF, FAK, and Paxillin were decreased in human TNBC cells administrated with I194496. Furthermore, I194496 showed more stronger inhibitory effects on human TNBC xenograft tumors in nude mice. I194496 could inhibit the growth of human TNBC cells via the dual targeting PI3K/Akt and Ras/Raf/ERK pathway and suppress the metastasis of human TNBC cells via down-regulating Anxa2/STAT3 and VEGF/FAK/Paxillin signaling pathways. CSE inhibitor I194496 might become a novel and potential agent in the treatment of TNBC.
Safety and efficacy of microinvasive glaucoma surgery with cataract extraction in patients with normal-tension glaucoma
Authors: Chang Enchi Kristina , Gupta Sanchay , Chachanidze Marika , Hall Nathan , Chang Ta Chen , Solá-Del Valle David
Published: April 2021

This study assesses the safety and efficacy of microinvasive glaucoma surgery (MIGS) with cataract extraction in patients with normal-tension glaucoma (NTG). In our sample of 45 NTG patients, mean intraocular pressure (IOP) decreased from 13.7 to 12.3 mmHg at 2.5 years, and mean medication burden decreased from 2.0 to 1.1 at 1.5 years. For success defined as IOP reduction ≥ 30% from baseline IOP with medication burden reduction from preoperative levels, success probability was 5.4% at 1.5 years. For success defined as medication burden reduction with an IOP reaching goal IOP as determined by the glaucoma specialist, success probabilities were 67.2% at 1.5 years and 29.4% at 2.5 years. At the last follow-up visit, eyes with two MIGS procedures with different mechanisms of action achieved successful medication reduction 68.8% of the time versus 35.7% achieved by a single MIGS procedure (p = 0.052). At their last visit, visual acuity was unchanged or improved in all eyes (100%). MIGS with cataract surgery results in modest reductions in IOP and medication burden in NTG patients, which may lead to lower costs and better therapeutic compliance. A combination of two MIGS procedures with different mechanisms of action may potentially be more effective in reducing medication burden than a single MIGS procedure in NTG patients. Further research is necessary to ascertain whether MIGS for NTG patients may help decrease medication burden while helping achieve goal IOP.
The effects of in-hospital deprescribing on potential prescribing omission in hospitalized elderly patients with polypharmacy
Authors: Kaminaga Miho , Komagamine Junpei , Tatsumi Shinpei
Published: April 2021

No studies to investigate the effect of a deprescribing intervention on the occurrence of potential prescribing omissions (PPOs) among elderly patients with polypharmacy have been conducted. Therefore, the effect of deprescribing on PPOs among elderly patients with polypharmacy was investigated. All 121 consecutive elderly patients who received in-hospital deprescribing interventions were evaluated. The primary outcome was any occurrence of PPOs based on the 2015 STOPP/START criteria. The proportion of patients who had any PPOs significantly increased after the deprescribing interventions (52.9% vs 77.7%, p < 0.001). In the multivariable analysis, older age was the only independent risk factor associated with an increased risk of any PPOs after the deprescribing interventions (OR 1.08, 95% CI 1.01 to 1.16). In-hospital deprescribing interventions for elderly patients with polypharmacy may increase the occurrence of PPOs. Further study is warranted to investigate the effects on clinical outcomes of the increased occurrence of PPOs due to the deprescribing intervention.
Accuracy and reliability of measurements obtained with a noncontact tono-pachymeter for clinical use in mass screening
Authors: Lee Jinho , Choi Hyuk Jin
Published: April 2021

We evaluated the reliability and accuracy of the noncontact CT-1P tonopachymeter (Topcon, Japan) in terms of intraocular pressure (IOP) and central corneal thickness (CCT). One hundred sixty-three healthy participants and 33 patients with open angle glaucoma were enrolled. IOPs were measured by CT-1P (T-IOP) and Goldmann applanation tonometer (G-IOP), and CCTs were measured by the CT-1P (T-CCT) and an ultrasound pachymeter (US-CCT). Both CCT instrument-adjusted (T-IOP-C) and unadjusted T-IOPs (T-IOP-NC) were included. Pearson correlation coefficients and biases assessed with Bland–Altman analysis with 95% confidence interval (CI) were calculated for reliability evaluation. Intrasession repeatability was excellent for both T-IOP (intraclass correlation coefficient [ICC] 0.91) and T-CCT (ICC 0.98). Intersession reproducibility was also excellent for T-CCT (ICC 0.94). T-IOP-NC and T-IOP-C both showed significant correlations with G-IOP (r = 0.801, P  <  0.001 and r = 0.658, P  < 0.001, respectively). T-CCT was also strongly correlated with US-CCT (r = 0.958; P  < 0.001). T-IOP-NC and T-IOP-C both showed a positive bias (1.37 mmHg, 95% CI [1.14, 1.61] and 2.77 mmHg, 95% CI [2.49, 3.05], respectively). T-CCT showed a negative bias of − 17.3 µm (95% CI [−18.8, − 15.8]). With cautious interpretation, the CT-1P may offer good feasibility for IOP and CCT measurement in screening centers.
Effect of four ABCB1 genetic polymorphisms on the accumulation of darunavir in HEK293 recombinant cell lines
Authors: Stillemans Gabriel , Djokoto Happy Phanio , Delongie Kévin-Alexandre , El-Hamdaoui Halima , Panin Nadtha , Haufroid Vincent , Elens Laure
Published: April 2021

The intracellular penetration of darunavir, a second-generation HIV protease inhibitor, is limited by the activity of the efflux P-glycoprotein (ABCB1). ABCB1 expression and/or activity levels can vary between individuals due to genetic polymorphisms including the c.1199G>A, c.1236C>T, c.2677G>T and c.3435C>T variants, which could in part explain why the pharmacokinetics of darunavir are so variable from one individual to another. While a few clinical studies have failed to demonstrate an influence of these polymorphisms on darunavir pharmacokinetics, drug-drug interactions and methodological limitations may have prevented them from revealing the true influence of ABCB1 variants. In this work, we report on the intracellular accumulation of darunavir in recombinant HEK293 cell lines expressing wild-type ABCB1 or one of several variants: ABCB1 1199A, ABCB1 3435T, and ABCB1 1236T/2677T/3435T. We demonstrate that while ABCB1 expression limits intracellular accumulation of darunavir, there is no significant difference in efflux activity between cells expressing wild-type ABCB1 and those that express any of the studied variants.
Dislocations in ceramic electrolytes for solid-state Li batteries
Authors: Porz L. , Knez D. , Scherer M. , Ganschow S. , Kothleitner G. , Rettenwander D.
Published: April 2021

High power solid-state Li batteries (SSLB) are hindered by the formation of dendrite-like structures at high current rates. Hence, new design principles are needed to overcome this limitation. By introducing dislocations, we aim to tailor mechanical properties in order to withstand the mechanical stress leading to Li penetration and resulting in a short circuit by a crack-opening mechanism. Such defect engineering, furthermore, appears to enable whisker-like Li metal electrodes for high-rate Li plating. To reach these goals, the challenge of introducing dislocations into ceramic electrolytes needs to be addressed which requires to establish fundamental understanding of the mechanics of dislocations in the particular ceramics. Here we evaluate uniaxial deformation at elevated temperatures as one possible approach to introduce dislocations. By using hot-pressed pellets and single crystals grown by Czochralski method of Li6.4La3Zr1.4Ta0.6O12 garnets as a model system the plastic deformation by more than 10% is demonstrated. While conclusions on the predominating deformation mechanism remain challenging, analysis of activation energy, activation volume, diffusion creep, and the defect structure potentially point to a deformation mechanism involving dislocations. These parameters allow identification of a process window and are a key step on the road of making dislocations available as a design element for SSLB.
Experimental and theoretical studies on induced ferromagnetism of new (1 − x)Na0.5Bi0.5TiO3 + xBaFeO3−δ solid solution
Authors: Dung Dang Duc , Lam Nguyen Huu , Nguyen Anh Duc , Trung Nguyen Ngoc , Van Duc Nguyen , Hung Nguyen The , Kim Yong Soo , Odkhuu Dorj
Published: April 2021

New solid solution of Na0.5Bi0.5TiO3 with BaFeO3−δ materials were fabricated by sol–gel method. Analysis of X-ray diffraction patterns indicated that BaFeO3−δ materials existed as a well solid solution and resulted in distortion the structure of host Na0.5Bi0.5TiO3 materials. The randomly incorporated Fe and Ba cations in the host Na0.5Bi0.5TiO3 crystal decreased the optical band gap from 3.11 to 2.48 eV, and induced the room-temperature ferromagnetism. Our density-functional theory calculations further suggested that both Ba for Bi/Na-site and Fe dopant, regardless of the substitutional sites, in Na0.5Bi0.5TiO3 lead to the induced magnetism, which is illustrated in terms of the exchange splitting between spin subbands through the crystal field theory and Jahn–Teller distortion effects. Our work proposes a simple method for fabricating lead-free ferroelectric materials with ferromagnetism property for multifunctional applications in smart electronic devices.
Effect of respiratory inhibitors and quinone analogues on the aerobic electron transport system of Eikenella corrodens
Authors: Jaramillo-Lanchero Rubén D. , Suarez-Alvarez Paola , Teheran-Sierra Luis
Published: April 2021

The effects of respiratory inhibitors, quinone analogues and artificial substrates on the membrane-bound electron transport system of the fastidious β-proteobacteriumEikenella corrodensgrown under O2-limited conditions were studied. NADH respiration in isolated membrane particles were partially inhibited by rotenone, dicoumarol, quinacrine, flavone, and capsaicin. A similar response was obtained when succinate oxidation was performed in the presence of thenoyltrifluoroacetone and N,N’-dicyclohexylcarbodiimide. NADH respiration was resistant to site II inhibitors and cyanide, indicating that a percentage of the electrons transported can reach O2without thebc1complex. Succinate respiration was sensitive to myxothiazol, antimycin A and 2-heptyl-4-hydroxyquinoline-N-oxide (HQNO). Juglone, plumbagin and menadione had higher reactivity with NADH dehydrogenase. The membrane particles showed the highest oxidase activities with ascorbate-TCHQ (tetrachlorohydroquinone), TCHQ alone, and NADH-TMPD (N,N,N’,N’-tetramethyl-p-phenylenediamine), and minor activity levels with ascorbate-DCPIP (2,6-dichloro-phenolindophenol) and NADH-DCPIP. The substrates NADH-DCPIP, NADH-TMPD and TCHQ were electron donors to cyanide-sensitivecbb'cytochromecoxidase. The presence of dissimilatory nitrate reductase in the aerobic respiratory system ofE.corrodensATCC 23834 was demonstrated by first time. Our results indicate that complexes I and II have resistance to their classic inhibitors, that the oxidation of NADH is stimulated by juglone, plumbagin and menadione, and that sensitivity to KCN is stimulated by the substrates TCHQ, NADH-DCPIP and NADH-TMPD.
Patch selection by bumble bees navigating discontinuous landscapes
Authors: Fragoso Fabiana P. , Jiang Qi , Clayton Murray K. , Brunet Johanne
Published: April 2021

Pollen and nectar resources are unevenly distributed over space and bees must make routing decisions when navigating patchy resources. Determining the patch selection process used by bees is crucial to understanding bee foraging over discontinuous landscapes. To elucidate this process, we developed four distinct probability models of bee movement where the size and the distance to the patch determined the attractiveness of a patch. A field experiment with a center patch and four peripheral patches of two distinct sizes and distances from the center was set up in two configurations. Empirical transition probabilities from the center to each peripheral patch were obtained at two sites and two years. The best model was identified by comparing observed and predicted transition probabilities, where predicted values were obtained by incorporating the spatial dimensions of the field experiment into each model’s mathematical expression. Bumble bees used both patch size and isolation distance when selecting a patch and could assess the total amount of resources available in a patch. Bumble bees prefer large, nearby patches. This information will facilitate the development of a predictive framework to the study of bee movement and of models that predict the movement of genetically engineered pollen in bee-pollinated crops.
Drug-utilisation profiles and COVID-19
Authors: Orlando Valentina , Coscioni Enrico , Guarino Ilaria , Mucherino Sara , Perrella Alessandro , Trama Ugo , Limongelli Giuseppe , Menditto Enrica
Published: April 2021

Coronavirus disease 2019 (COVID-19) has substantially challenged healthcare systems worldwide. By investigating population characteristics and prescribing profiles, it is possible to generate hypotheses about the associations between specific drug-utilisation profiles and susceptibility to COVID-19 infection. A retrospective drug-utilisation study was carried out using routinely collected information from a healthcare database in Campania (Southern Italy). We aimed to discover the prevalence of drug utilisation (monotherapy and polytherapy) in COVID-19 versus non-COVID-19 patients in Campania (~ 6 million inhabitants). The study cohort comprised 1532 individuals who tested positive for COVID-19. Drugs were grouped according to the Anatomical Therapeutic Chemical (ATC) classification system. We noted higher prevalence rates of the use of drugs in the ATC categories C01, B01 and M04, which was probably linked to related comorbidities (i.e., cardiovascular and metabolic). Nevertheless, the prevalence of the use of drugs acting on the renin-angiotensin system, such as antihypertensive drugs, was not higher in COVID-19 patients than in non-COVID-19 patients after adjustments for age and sex. These results highlight the need for further case–control studies to define the effects of medications and comorbidities on susceptibility to and associated mortality from COVID-19.
Reef foraminifera as bioindicators of coral reef health in southern South China Sea
Authors: A’ziz Aishah Norashikin Abdul , Minhat Fatin Izzati , Pan Hui-Juan , Shaari Hasrizal , Saelan Wan Nurzalia Wan , Azmi Nazihah , Manaf Omar Abdul Rahman Abdul , Ismail Md Nizam
Published: April 2021

Pulau Tioman is a famous tourist island off Peninsular Malaysia with beautiful coral reefs. This study aims to assess the health of the coral reefs surrounding Pulau Tioman based on the application of the Foraminifera in Reef Assessment and Monitoring Index (FI). Ten sampling sites around Pulau Tioman were studied with a total of 30 samples. Eight orders, 41 families, 80 genera, and 161 species of benthic foraminifera were identified. The agglutinated type of foraminifera constituted 2–8% of the total assemblages. Calcareous hyaline and porcelaneous groups represented 79% and 19% of the total assemblages, respectively. Symbiont-bearing taxa were the most common foraminifera. The results indicate that most of the sampling sites are conducive for coral reef growth with good recoverability from future stress to the ecosystem. However, several areas with higher coastal development and tourism have reduced water and sediment quality. Therefore, the limit on the number of visitors and tourists should be revised to enable coral growth and health. The FI values in this study showed a positive correlation with good water qualities and a negative correlation with organic matter enrichment. The FI is a good measure to assess the health of a coral reef and can be applied to other reef ecosystems around Malaysia.
Circulating endothelial cells transiently increase in peripheral blood after kidney transplantation
Authors: Tejeda-Mora H. , Verhoeven J. G. H. P. , Verschoor W. , Boer K. , Hesselink D. A. , van den Hoogen M. W. F. , van der Laan L. J. W. , Baan C. C. , Minnee R. C. , Hoogduijn M. J.
Published: April 2021

The diagnosis of kidney allograft rejection is based on late histological and clinical markers. Early, specific and minimally-invasive biomarkers may improve rejection diagnosis. Endothelial cells (EC) are one of the earliest targets in kidney transplant rejection. We investigated whether circulating EC (cEC) could serve as an earlier and less invasive biomarker for allograft rejection. Blood was collected from a cohort of 51 kidney transplant recipients before and at multiple timepoints after transplantation, including during a for cause biopsy. The number and phenotype of EC was assessed by flow-cytometric analysis. Unbiased selection of EC was done using principal component (PCA) analysis. Paired analysis revealed a transient cEC increase of 2.1-fold on the third day post-transplant, recovering to preoperative levels at seventh day post-transplant and onwards. Analysis of HLA subtype demonstrated that cEC mainly originate from the recipient. cEC levels were not associated with allograft rejection, allograft function or other allograft pathologies. However, cEC in patients with allograft rejection and increased levels of cEC showed elevated levels of KIM-1 (kidney injury marker-1). These findings indicate that cEC numbers and phenotype are affected after kidney transplantation but may not improve rejection diagnosis.
Escalation of liPid-lOwering therapy in patientS wiTh vascular disease receiving HIGH-intensity statins: the retrospective POST-HIGH study
Authors: Ha Jaehyung , Lee Bom , Park Jung Mi , Kang Moonjong , Oh Jaewon , Lee Chan Joo , Park Sungha , Kang Seok-Min , Lee Sang-Hak
Published: April 2021

In this retrospective study, we investigated whether lipid-lowering therapy (LLT) escalation has clinical benefits in patients with atherosclerotic cardiovascular disease (ASCVD) and low-density lipoprotein cholesterol (LDL-C) levels of 55–99 mg/dL (1.4–2.6 mmol/L), post high-intensity. Out of 6317 Korean patients screened in 2005–2018, 1159 individuals with ASCVD and LDL-C levels of 55–99 mg/dL after statin use equivalent to 40 mg atorvastatin were included. After 1:2 propensity score matching, 492 patients (164 with LLT escalation, 328 controls without LLT escalation) were finally analysed. Primary outcome variables were major adverse cardiovascular and cerebrovascular events (MACCE) and all-cause death. At median follow-up (1.93 years), the escalation group had a lower MACCE rate (1.72 vs. 3.38 events/100 person-years; hazard ratio [HR] 0.34, 95% confidence interval [CI] 0.14–0.83; p = 0.018) than the control group. The incidence of all-cause death (0.86 vs. 1.02 events/100 person-years; HR 0.58, 95% CI 0.15–2.19; p = 0.42) and each MACCE component did not differ between groups. Kaplan–Meier curves exhibited lower risk of MACCE in the escalation group (HR 0.36, 95% CI 0.12–0.97; p = 0.040) but a difference not statistically significant in all-cause death (HR 0.30, 95% CI 0.04–2.48; p = 0.26). LLT escalation was associated with reduced cardiovascular risk, supporting more aggressive LLT in this population.
Cesarean section delivery is a risk factor of autism-related behaviors in mice
Authors: Nagano Masatoshi , Saitow Fumihito , Higo Shinpei , Uzuki Makoto , Mikahara Yasunori , Akimoto Toshio , Ozawa Hitoshi , Nishimori Katsuhiko , Suzuki Hidenori
Published: April 2021

Cesarean section (C/S) is one way of delivering babies, and is chosen when mothers or babies are facing problems or life-threatening conditions during pregnancy. Many meta-analyses have suggested an etiological relationship between C/S delivery and autism spectrum disorders (ASDs). However, as a risk factor for ASDs, C/S delivery has not yet been well studied. Because C/S deliveries have been increasing, it is very important to investigate the causal association between C/S and ASDs. Here, using three approaches, we showed experimentally that C/S delivery induced ASD-like traits in offspring mice, and that some of these changes were ameliorated by one-time oxytocin (OXT) treatment. Treatment with OXT receptor antagonists before natural delivery also induced ASD-related behaviors. Moreover, wild-type mice born to OXT-KO dams showed similar changes. Thus, insufficient OXT exposure from dams to offspring during delivery may be a trigger for ASD-related behaviors.
Altered sleep behavior in a genetic mouse model of impaired fear extinction
Authors: Fritz Eva Maria , Kreuzer Matthias , Altunkaya Alp , Singewald Nicolas , Fenzl Thomas
Published: April 2021

Sleep disturbances are a common complaint of anxiety patients and constitute a hallmark feature of post-traumatic stress disorder (PTSD). Emerging evidence suggests that poor sleep is not only a secondary symptom of anxiety- and trauma-related disorders but represents a risk factor in their development, for example by interfering with emotional memory processing. Fear extinction is a critical mechanism for the attenuation of fearful and traumatic memories and multiple studies suggest that healthy sleep is crucial for the formation of extinction memories. However, fear extinction is often impaired in anxiety- and trauma-related disorders—an endophenotype that is perfectly modelled in the 129S1/SvImJ inbred mouse strain. To investigate whether these mice exhibit altered sleep at baseline that could predispose them towards maladaptive fear processing, we compared their circadian sleep/wake patterns to those of typically extinction-competent C57BL/6 mice. We found significant differences regarding diurnal distribution of sleep and wakefulness, but also sleep architecture, spectral features and sleep spindle events. With regard to sleep disturbances reported by anxiety- and PTSD patients, our findings strengthen the 129S1/SvImJ mouse models’ face validity and highlight it as a platform to investigate novel, sleep-focused diagnostic and therapeutic strategies. Whether the identified alterations causally contribute to its pathological anxiety/PTSD-like phenotype will, however, have to be addressed in future studies.