bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving the Long‐Term Stability of BPQD‐Based Memory Device via Modification with Polyvinylpyrrolidone‐Grafted Polydopamine
Authors: Che Qiang , Wang Xinzhu , El‐Khouly Mohamed E. , Li Guangwei , Liu Jiaxuan , Zhang Bin , Chen Yu
Published: December 2021

Long‐term environmental stability of electronic and optoelectronic devices is a very important concern. Both black phosphorus (BP) nanosheets and quantum dots (BPQDs) exhibit very poor environmental stability. To address this problem, a new encapsulation approach for improving long‐term stability of the BPQD‐based electronic devices, which concerns two‐step in situ polymerizations: 1) in situ polymerization of dopamine in the presence of BPQDs giving a BPQDs@PDA (PDA: polydopamine) composite; 2) in situ atom transfer radical polymerization of N‐vinyl‐2‐pyrrolidone on the BPQDs@PDA surface producing the BPQDs@PDA–PVP composite (PVP: polyvinylpyrrolidone), is developed. Both the Al/BPQDs@PDA–PVP/ITO and Al/BPQDs:PVP blends/ITO devices show excellent nonvolatile memory performance at the initial measurement stage. Interestingly, the former can only be programmed to the high conductivity state in the positive bias range, while the latter can be switched into the ON state only in the negative bias range. The different switching directions may be highly associated with the inherent electronic structural characteristics of the materials. In contrast to the BPQDs:PVP blends and/or BPQDS@PDA:PVP blend‐based electronic devices with very unstable memory performance, the memory performance of the BPQDs@PDA–PVP‐based device remains unchanged even standing for 90 d.
A 25 cm2 Solar Redox Flow Cell: Facing the Engineering Challenges of Upscaling
Authors: da Silva Lopes Telmo , Dias Paula , Monteiro Ricardo , Vilanova António , Ivanou Dzmitry , Mendes Adélio
Published: December 2021

The solar redox flow cell (SRFC) is an emerging technology that uses semiconductors to photocharge redox pairs, storing solar energy in electrochemical fuels and heat. Despite being in its infancy, significant efforts have been made in the development of high‐efficient materials and in understanding the fundamental processes. However, little attention has been given to device architecture and scalability, which may prove equally important in bringing this technology closer to commercialization. This work is the first attempt at upscaling SRFCs, proposing an innovative 25 cm2 photoactive‐area device: the SolarFlow25 cell. A computational fluid dynamics model is developed to implement design key features aiming at: maximizing light absorption by the semiconductor, ensuring effective diffusion and convection of redox species, and guaranteeing minimal electronic and ionic transport resistances. After being connected to a redox flow cell (RFC), the combined SRFC/RFC device is used to photocharge–discharge a ferrocyanide/anthraquinone (2,7‐AQDS) chemistry continuously. A nanostructured hematite (α‐Fe2O3) photoelectrode combined in series with a dye‐sensitized solar cell (DSSC) produces an unbiased photocurrent of ≈40 mA. The solar‐to‐output‐electricity‐efficiency remains stable at ≈0.44%, fourfold higher than any other reported hematite‐driven SRFC. The guidelines provided here are expected to help design and upscale future SRFC devices, making solar energy accessible in decentralized locations.
Changes in silage quality, bacterial community dynamics, and metabolic profiles in whole‐crop maize silage
Authors: Wang Siran , Li Junfeng , Zhao Jie , Dong Zhihao , Shao Tao
Published: December 2021

This study aimed to investigate the silage quality, bacterial community, and predicted functional profiles during the ensiling of whole‐crop maize (Zea mays L.). Maize was harvested at dough stage and ensiled in laboratory‐scale silos (1‐L capacity). Triplicate silos were sampled after 1, 3, 7, 15, 30, and 60 d of ensiling. The bacterial communities on Day 3 and Day 60 were assessed through high throughput sequencing technology, and 16S rRNA gene‐predicted functional profiles were analyzed according to the KEGG using Tax4Fun. After 60 d of ensiling, the maize silages had large amounts of lactic acid (∼69.0 g dry matter [DM] kg–1), and low pH (∼3.64), butyric acid (∼1.31 g DM kg–1), and ammonia N (∼64.9 g total N kg–1). Lactobacillus was the most dominant genus during the early and late stages of fermentation. After ensiling, the metabolism of amino acid, energy, cofactors and vitamins was inhibited by 17.5, 16.3, and 16.0% respectively, whereas the metabolism of nucleotide and carbohydrate was enhanced by 37.1 and 10.3%, respectively. The promotion of 1‐phosphofructokinase and pyruvate kinase (65.9 and 32.5%, respectively) may stimulate the lactic acid fermentation, and the enhancement of arginine deiminase (61.8%) could help lactic acid bacteria to tolerate the acid environment. Overall, the high throughput sequencing technology, combined with 16S rRNA gene‐predicted functional analyses, revealed differences in maize silage related to shifts in the bacterial community consistent with increased abundance of inferred enzymatic pathways. This approach could provide comprehensive insights into bacterial community and functional profiles to further improve the silage quality.
Trapeziometacarpal joint mobility in gibbons (fam. Hylobatidae) and rhesus macaques (Macaca mulatta)
Authors: van Leeuwen Timo , Vanneste Maarten , D'Agostino Priscilla , Vereecke Evie E.
Published: December 2021

Objectives

The purpose of this study is to investigate the differences in 3D kinematics of the trapeziometacarpal (TMC) joint between gibbons (fam. Hylobatidae) and macaques (Macaca mulatta), two non‐human primate groups with a distinct locomotor behavior. Gibbons are highly arboreal species, while macaques are quadrupeds. Here, we investigate the mobility and structural constraints of the TMC joint in both these primates and evaluate the hypothesis that differences in locomotor mode are reflected in joint structure and function.

Materials and methods

We have developed an innovative software suite allowing for the quantification of in situ 3D kinematics based on medical imaging of the primate TMC joint using a unique sample of eight gibbons and seven macaques. These analyses are further supported by detailed dissection of the surrounding ligaments.

Results

The data demonstrate distinct differences in TMC joint mobility between gibbons and macaques, with wide ranges of motion in the gibbon TMC joint and restricted movement in macaques. Furthermore, the dissections show little dissimilarity in ligament anatomy that could be associated with the differences in TMC joint capabilities.

Conclusion

We conclude that gibbons possess a highly mobile TMC joint and the ball‐and‐socket morphology allows for large ranges of motion. This type of morphology, however, does not offer much inherent stabilization. Lack of structural joint reinforcement suggests that gibbons may have difficulty in performing any type of power grasp with high loads. Macaques, on the other hand, are shown to have a considerably reinforced TMC joint, which is likely related to the habitual loading of the thumb during locomotion.
Functional Characterization and Protein Engineering of a Triterpene 3‐/6‐/2′‐O‐Glycosyltransferase Reveal a Conserved Residue Critical for the Regiospecificity
Authors: Zhang Meng , Yi Yang , Gao Bai‐Han , Su Hui‐Fei , Bao Yang‐Oujie , Shi Xiao‐Meng , Wang Hai‐Dong , Li Fu‐Dong , Ye Min , Qiao Xue
Published: December 2021

Engineering the function of triterpene glucosyltransferases (GTs) is challenging due to the large size of the sugar acceptors. In this work, we identified a multifunctional glycosyltransferase AmGT8 catalyzing triterpene 3‐/6‐/2′‐O‐glycosylation from the medicinal plantAstragalus membranaceus. To engineer its regiospecificity, a small mutant library was built based on semi‐rational design. Variants A394F, A394D, and T131V were found to catalyze specific 6‐O, 3‐O, and 2′‐Oglycosylation, respectively. The origin of regioselectivity of AmGT8 and its A394F variant was studied by molecular dynamics and hydrogen deuterium exchange mass spectrometry. Residue 394 is highly conserved as A/G and is critical for the regiospecificity of theC‐ andO‐GTs TcCGT1 and GuGT10/14. Finally, astragalosides III and IV were synthesized by mutants A394F, T131V and P192E. This work reports biocatalysts for saponin synthesis and gives new insights into protein engineering of regioselectivity in plant GTs.
A Lanthanum Ammonium Sulfate Double Salt with a Strong SHG Response and Wide Deep‐UV Transparency
Authors: Wu Chao , Jiang Xingxing , Hu Yilei , Jiang Chunbo , Wu Tianhui , Lin Zheshuai , Huang Zhipeng , Humphrey Mark G. , Zhang Chi
Published: December 2021

The targeted synthesis of deep‐ultraviolet (deep‐UV) nonlinear optical (NLO) materials, especially those with non‐π‐conjugated sulfates, has experienced considerable difficulties due to the need to reconcile the oft‐competing requirements for deep‐UV transparency and strong second‐harmonic generation (SHG). We report herein the designed synthesis of the first rare‐earth metal‐based deep‐UV sulfate La(NH4)(SO4)2 by a double‐salt strategy involving introduction of complementary cations, together with optical studies that reveal a short‐wavelength deep‐UV absorption edge (below 190 nm) and the strongest SHG response among deep‐UV NLO sulfates (2.4×KDP). Theoretical calculations and crystal structure analysis suggest that the excellent balance between SHG response and deep‐UV transparency can be attributed to a synergistic interaction of the hetero‐cations La3+ and [NH4]+, which optimize alignment of the [SO4] tetrahedra and highly polarizable [LaO8] polyhedra.
Construction, expression, purification, characterization, and structural analysis of microbial transglutaminase variants
Authors: Song Xiaoping , Sheng Hefang , Zhou Yueqiao , Yu Yin , He Yingjiao , Wang Zihan
Published: December 2021

Microbial transglutaminase (MTG, EC 2.3.2.13) derived from Streptomyces mobaraensis is widely used in the food and pharmaceutical industry because of its ability to synthesize isopeptide bonds between the proteinogenic side chains of glutamine and lysine. The half‐life (t1/2) of the activated wild‐type enzyme at 60°C is 2 min. To improve the activity and thermostability of MTG for higher temperature application, three variants (Mut1, Mut2, and Mut3) were obtained by combining key amino acid mutations on the basis of previous research results. The best variant Mut2 with a specific combination of five of seven substitutions (S2P–S23V–Y24N–R215A–H289Y) shows a 10‐fold increased half‐life at 60°C (t1/2 = 27.6 min), and a 2.4‐fold increased specific enzyme activity (39.3 U/mg). As measured by circular dichroism, the curve of Mut2 was basically the same as that of MTG‐WT. The structural simulation of Mut2 shows that the overall structure is discoid with a crack, but the crack openings are wider than that of MTG‐WT. Furthermore, structural analysis of Mut2 showed that there were seven hydrogen bonds and one π‐anion interaction between Mut2 and its adjacent amino acids, and the number of hydrogen bonds was one more than that of MTG‐WT (six hydrogen bonds).
A highly selective fluorescent sensor for Cu2+ based on naphthalimide containing aza‐crown ether
Authors: Jeon Sumin , Lee Seongman , Choi Yeonghwan , Kim Mi‐Ra , Lee Songyi
Published: December 2021

The development of a fluorogenic chemosensors with high sensitivity for copper ion (Cu2+) has been receiving great attention in recent years because of their potential application in clinical biochemistry and the environment studies. In the present study, we designed and synthesized a fluorescent probe, Np‐azaCE, with 1,8‐naphthalimides as a core structure and 1,4‐diaza‐9‐crown‐3‐ether as a copper ion tweeze, which showed selective and sensitive fluorometric change upon addition of a copper ion. The Np‐azaCE chemosensor was highly selective for Cu2+ over the other metal ions with fluorescent quenching. Finally, the Cu2+ detection limit and job's plot of Np‐azaCE were calculated using UV–visible spectrophotometer and fluorescence spectrophotometer.
Treating teens who struggle with mental health and substance use: Expert care at Bradley Vista
Authors: Miranda Robert
Published: December 2021

Diagnosed with attention‐deficit hyperactivity disorder (ADHD) and anxiety, Alex has recently struggled to manage his emotions and often seems down and irritable. In recent months he spends much less time with his family, often stays in his room, and opts not to join the family for meals or other activities. His mother believes he is depressed, although she acknowledges that he doesn't share much. She knows he first tried cannabis when he was 13 years old and believes he engages in occasional recreational use. Her concerns recently heightened, however, when she found drug paraphernalia in his room and his academic performance markedly declined.
Keep your eye on…
Authors: Knopf Alison
Published: December 2021

Universal depression screening in schools

The link between emotion regulation and anorexia nervosa
Maturity‐onset diabetes of the young (MODY) due to PDX1 mutation in a sib‐pair diabetes family from Qatar
Authors: Haris Basma , Mohammed Idris , Syed Najeeb , Fakhro Khalid , Hussain Khalid
Published: December 2021

Maturity‐onset diabetes of young (MODY) is an autosomal dominant genetic disorder that causes insulin deficiency without autoimmunity. We present the first family with pancreatic duodenal homeobox 1 (PDX1) mutation causing diabetes from Qatar. Routine genetic screening of all antibody‐negative diabetic patients with diabetes should be offered to avoid misdiagnosis.
A rare giant gastric trichobezoar in a young female patient: Case report and review of the literature
Authors: Delimpaltadaki Dimitra G. , Gkionis Ioannis G. , Flamourakis Mathaios E. , Strehle Andreas F. , Bachlitzanakis Emmanouil N. , Giakoumakis Michail I. , Christodoulakis Manousos S. , Spiridakis Konstantinos G.
Published: December 2021

A bezoar is an aggregate of undigested foreign materials that accumulate in the gastrointestinal tract and may cause serious symptoms or even life‐threatening complications. Trichobezoars, a subtype of bezoars, are a rare condition usually occurring in females with psychiatric disorders, with Rapunzel syndrome being an uncommon form of trichobezoar.
Diffuse large B‐cell lymphoma initially presenting with peritoneal dissemination
Authors: Hirata Risa , Tago Masaki , Tokushima Yoshinori
Published: December 2021

A 62‐year‐old woman with a severely distended abdomen and no palpable superficial lymph nodes visited the hospital. Computed tomography with contrast enhancement revealed multiple fused and homogeneously contrasting masses filling the abdominal cavity. She was diagnosed with diffuse large B‐cell lymphoma by ultrasound‐guided needle biopsy performed on admission.
µCT‐Based Topography Analysis of Inaccessible Surfaces Exemplified by a Biofouling‐Covered Plastic
Authors: Bittner Florian , Endres Hans‐Josef
Published: December 2021

The measurement of surface topographies is usually restricted to surfaces that are directly accessible to tactile or optical sensing. With this paper, the application of micro‐computed tomography to measure characteristics of surfaces that are covered by solid films and thus not directly accessible is demonstrated. The method is first validated by comparative measurements of a plastic sample with µCT and conventional optical profilometry. Afterwards, the µCT‐based method is successfully applied to a polyhydroxybutyrate plastic sample covered by biofouling after exposure to marine environment, providing insight into the degradation processes.
High‐dose non‐sedating antihistamines are used insufficiently in chronic urticaria patients treated with omalizumab
Authors: Madsen Hanne , Mortz Charlotte G. , Bindslev‐Jensen Carsten , Reilev Mette , Hallas Jesper , Henriksen Daniel P.
Published: December 2021

Background

The lifetime prevalence of chronic urticaria (CU) is 0.5%–1%. In some patients with CU, symptomatic control is not achieved with non‐sedating second‐generation H1 antihistamines (nsAH1) alone, even with quadrupled standard doses as recommended in international guidelines. In these cases, biological treatment with omalizumab can be added. Since omalizumab is expensive compared to antihistamines, lack of adherence to guidelines for high dose nsAH1 (up to four‐fold standard dose per day) may be associated with substantial unnecessary costs. The aim was to measure the use nsAH1 before and during omalizumab use for the first time in an omalizumab treated CU population.

Methods

We identified all Danish patients with CU who initiated omalizumab from March 2014 to December 2018 and evaluated new and ongoing nsAH1 treatments using the Danish nationwide registries.

Results

A total of 955 CU patients initiated treatment with omalizumab within the study period (median age 40 years [IQR 28–50], 74.5% females). During the 12 months prior to omalizumab initiation, 95.6% of the patients filled at least one prescription with nsAH1 at some point, while 84.7% filled at least one prescription during the three months before omalizumab. From 3 months before omalizumab initiation till 3 months after, the proportions of users of high‐dose nsAH1 was maximum 31.1%.

Conclusions

Omalizumab was usually administered before sufficient nsAH1 treatment was tried. In despite of the labelling that omalizumab should be co‐administered with high dose nsAH1, this does not happen This may lead to substantial unnecessary costs.
Novel low‐power and stable memory cell design using hybrid CMOS and MTJ
Authors: Prasad Govind , Sahu Deeksha , Chandra Mandi Bipin , Ali Maifuz
Published: December 2021

Memory is an essential component of any VLSI data storage system. Because of the shrinking of CMOS processing nodes, power consumption in conventional memory (SRAM and DRAM) increases. Traditional memory technologies also suffer several additional difficulties, such as limited scalability, low reliability, short data retention time, low durability, increased space, and latency, among others. As a result, new device technologies are critical for developing low‐power, high‐performance memory devices. Among the numerous developing nonvolatile (NV) memory technologies available today, STT‐MRAM is regarded as one of the most appealing and promising NV memory technologies for overcoming the limitations of traditional memories. STT‐MRAM is more efficient, quicker, NV, highly scalable, and readily integrated with CMOS technology. Because of the scalability of technology nodes below 45 nm, traditional STT‐MRAM cells have several difficulties, including high write power consumption, destructive read and write operation, prolonged write time, and so on. To address the issues associated with the writing operation of STT‐MRAM cells, this article presented an optimum STT‐MRAM cell design based on PMA‐MTJ. The write failure mitigation strategies are utilized to increase the proposed cell's write stability. A comparative analysis between conventional STT‐MRAM cell and the proposed cell is performed by concerning the write power consumption, write delay, and write stability. The experimental results indicate the performance superiority of the proposed cell architecture.
Flow cytometric analysis of myelodysplasia: Pre‐analytical and technical issues—Recommendations from the European LeukemiaNet
Authors: van der Velden Vincent H. J. , Preijers Frank , Johansson Ulrika , Westers Theresia M. , Dunlop Alan , Porwit Anna , Béné Marie C. , Valent Peter , te Marvelde Jeroen , Wagner‐Ballon Orianne , Oelschlaegel Uta , Saft Leonie , Kordasti Sharham , Ireland Robin , Cremers Eline , Alhan Canan , Duetz Carolien , Hobo Willemijn , Chapuis Nicolas , Fontenay Michaela , Bettelheim Peter , Eidenshink‐Brodersen Lisa , Font Patricia , Loken Michael R. , Matarraz Sergio , Ogata Kiyoyuki , Orfao Alberto , Psarra Katherina , Subirá Dolores , Wells Denise A. , Della Porta Matteo G. , Burbury Kate , Bellos Frauke , Weiß Elisabeth , Kern Wolfgang , van de Loosdrecht Arjan
Published: December 2021

Background

Flow cytometry (FCM) aids the diagnosis and prognostic stratification of patients with suspected or confirmed myelodysplastic syndrome (MDS). Over the past few years, significant progress has been made in the FCM field concerning technical issues (including software and hardware) and pre‐analytical procedures.

Methods

Recommendations are made based on the data and expert discussions generated from 13 yearly meetings of the European LeukemiaNet international MDS Flow working group.

Results

We report here on the experiences and recommendations concerning (1) the optimal methods of sample processing and handling, (2) antibody panels and fluorochromes, and (3) current hardware technologies.

Conclusions

These recommendations will support and facilitate the appropriate application of FCM assays in the diagnostic workup of MDS patients. Further standardization and harmonization will be required to integrate FCM in MDS diagnostic evaluations in daily practice.
Recent applications of phosphodiesterase (PDE5) inhibition assays for detecting adulterated sexual enhancement products
Authors: Santillo Michael F.
Published: December 2021

Consumer products marketed for sexual enhancement are frequently adulterated with erectile dysfunction (ED) drugs and analogs; consuming these undisclosed adulterants can pose significant health hazards. Although ED drugs/analogs have unpredictable and diverse structures that pose challenges for detecting them, they all share the ability to inhibit phosphodiesterase‐5 (PDE5) activity, a pharmacological mechanism responsible for their effects. Consequently, several PDE5 inhibition assays have been recently applied as screening methods to detect ED drug/analogs in products. Here, the successes and challenges are highlighted for screening sexual enhancement products by PDE5 inhibition assays.
Of wolves and bears: Seasonal drivers of interference and exploitation competition between apex predators
Authors: Tallian Aimee , Ordiz Andrés , Metz Matthew C. , Zimmermann Barbara , Wikenros Camilla , Smith Douglas W. , Stahler Daniel R. , Wabakken Petter , Swenson Jon E. , Sand Håkan , Kindberg Jonas
Published: December 2021

Competition between apex predators can alter the strength of top‐down forcing, yet we know little about the behavioral mechanisms that drive competition in multipredator ecosystems. Interactions between predators can be synergistic (facilitative) or antagonistic (inhibitive), both of which are widespread in nature, vary in strength between species and across space and time, and affect predation patterns and predator–prey dynamics. Recent research has suggested that gray wolf (Canis lupus) kill rates decrease where they are sympatric with brown bears (Ursus arctos), however, the mechanisms behind this pattern remain unknown. We used data from two long‐term research projects in Scandinavia (Europe) and Yellowstone National Park (North America) to test the role of interference and exploitation competition from bears on wolf predatory behavior, where altered wolf handling and search time of prey in the presence of bears are indicative of interference and exploitation competition, respectively. Our results suggest the mechanisms driving competition between bears and wolves were dependent on the season and study system. During spring in Scandinavia, interference competition was the primary mechanism driving decreased kill rates for wolves sympatric with bears; handling time increased, but search time did not. In summer, however, when both bear and wolf predation focused on neonate moose, the behavioral mechanism switched to exploitation competition; search time increased, but handling time did not. Alternartively, interference competition did affect wolf predation dynamics in Yellowstone during summer, where wolves prey more evenly on neonate and adult ungulates. Here, bear presence at a carcass increased the amount of time wolves spent at carcasses of all sizes and wolf handling time for small prey, but decreased handling time for the largest prey. Wolves facilitate scavenging opportunities for bears, however, bears alter wolf predatory behavior via multiple pathways and are primarily antagonistic to wolves. Our study helps to clarify the behavioral mechanisms driving competition between apex predators, illustrating how interspecific interactions can manifest into population‐level predation patterns.
Maintenance of high diversity in mechanistic forest dynamics models of competition for light
Authors: Detto Matteo , Levine Jonathan M. , Pacala Stephen W.
Published: December 2021

Although early theoretical work suggests that competition for light erodes successional diversity in forests, verbal models and recent numerical work with complex mechanistic forest simulators suggest that disturbance in such systems can maintain successional diversity. Nonetheless, if and how allocation trade‐offs between competitors interact with disturbance to maintain high diversity in successional systems remains poorly understood. Here, using mechanistic and analytically tractable models, we show that a theoretically unlimited number of coexisting species can be maintained by allocational trade‐offs such as investing in light‐harvesting organs versus height growth, investing in reproduction versus growth or survival versus growth. The models describe the successional dynamics of a forest composed of many patches subjected to random or periodic disturbance, and are consistent with physiologically mechanistic terrestrial ecosystem models, including the terrestrial components of recent Earth System Models. We show that coexistence arises in our models because species specialize in the successional time they best exploit the light environment and convert resources into seeds or contribute to advance regeneration. We also show that our results are relevant to non‐forested ecosystems by demonstrating the emergence of similar dynamics in a mechanistic model of competition for light among annual plant species. Finally, we show that coexistence in our models is relatively robust to the introduction of intraspecific variability that weakens the competitive hierarchy caused by asymmetric competition for light.
Exercise capacity after total cavopulmonary anastomosis: a longitudinal paediatric and adult study
Authors: Illinger Vojtěch , Materna Ondřej , Slabý Kryštof , Jičínská Denisa , Kovanda Jan , Koubský Karel , Pokorný Jan , Procházka Michal , Antonová Petra , Hoskovec Antonín , Radvanský Jiří , Chaloupecký Václav , Janoušek Jan
Published: December 2021

Aims

Fontan palliation is a surgical strategy for patients with complex congenital heart disease, in whom biventricular circulation cannot be achieved. Long‐term survival is negatively affected by the absence of sub‐pulmonary ventricle and increased systemic venous pressure. Exercise capacity is a known predictor of overall survival and quality of life in congenital heart defects. We aim to track individual trends of peak oxygen uptake (V̇O2peak) after total cavopulmonary connection (TCPC), identify predictors of deterioration, and derive a disease‐specific reference V̇O2peak dataset.

Methods and results

A retrospective study of serial cardiopulmonary exercise testing (CPET) data, gathered from all patients who underwent TCPC in the Czech Republic between 1992 and 2016. Of 354 consecutive patients with TCPC, 288 (81.4%) patients underwent one or more CPETs yielding 786 unique V̇O2peak values used as a reference dataset. Longitudinal data were available in 206 (58.2%) patients, who underwent a median (inter‐quartile range) of 3.0 (2.0–5.0) CPETs over a mean (standard deviation) of 8.9 (5.5) years. The decline of exercise capacity with age was linear and not faster than in healthy peers (P = 0.47), but relative values of V̇O2peak in TCPC patients were 12.6 mL/min/kg lower. Single ventricular morphology and pulmonary artery size had no significant influence on the exercise capacity dynamics. V̇O2peak decline correlated negatively with the trend of body mass index z‐score (P = 0.006) and was faster in women than men (P = 0.008).

Conclusions

Total cavopulmonary connection patients have significantly reduced exercise capacity. The age‐related decline paralleled the healthy population and correlated negatively with the body mass index trend. The presented V̇O2peak reference dataset may help the clinicians to grade the severity of exercise capacity impairment in individual TCPC patients.
Sodium–glucose co‐transporter 2 inhibitors as an early, first‐line therapy in patients with heart failure and reduced ejection fraction
Authors: Tomasoni Daniela , Fonarow Gregg C. , Adamo Marianna , Anker Stefan D. , Butler Javed , Coats Andrew J.S. , Filippatos Gerasimos , Greene Stephen J. , McDonagh Theresa A. , Ponikowski Piotr , Rosano Giuseppe , Seferovic Petar , Vaduganathan Muthiah , Voors Adriaan A. , Metra Marco
Published: December 2021

Sodium–glucose co‐transporter 2 (SGLT2) inhibitors have recently been recommended as a foundational therapy for patients with heart failure (HF) and reduced ejection fraction (HFrEF) because of their favourable effects on mortality, clinical events and quality of life. While clinical practice guidelines have recommended dapagliflozin or empagliflozin in all patients with HFrEF, or sotagliflozin in those with HFrEF and concomitant diabetes, the timing and practical integration of these drugs in clinical practice is less well defined. We propose that these drugs are candidates for early, upfront administration to patients with newly diagnosed HFrEF and for patients hospitalized with HF. Growing evidence has established early benefits, with clinically meaningful reductions in clinical events that reach statistical significance within days to weeks, following dapagliflozin, empagliflozin or, in diabetic patients, sotagliflozin initiation. Secondly, although major clinical trials have tested these drugs in patients already receiving background HF therapy, secondary analyses showed that their efficacy is independent of that. Third, SGLT2 inhibitors are generally safe and well tolerated, with clinical trial data reporting minimal effects on blood pressure, glycaemia‐related adverse events, and no excess in acute kidney injury. Rather, they exert renal protective effects and reduce risk of hyperkalaemia, properties that favour initiation, tolerance and persistence of renin–angiotensin system inhibitors and mineralocorticoid receptor antagonists. This review supports the early initiation of dapagliflozin and empagliflozin (or sotagliflozin limited to patients with diabetes) to rapidly improve clinical outcome and quality of life of HFrEF patients.
The effect of pH adjusted electrolytes on capillary isoelectric focusing assessed by high‐resolution dynamic computer simulation
Authors: Takácsi‐Nagy Anna , Kilár Ferenc , Thormann Wolfgang
Published: December 2021

The effect of the composition of electrolytes on capillary IEF is assessed for systems with carrier ampholytes covering two pH units and with catholytes of decreased pH, anolytes of increased pH, and both electrode solutions with adjusted pH values. For electrolytes composed of formic acid as anolyte and ammonium hydroxide as catholyte, simulation is demonstrated to provide the expected IEF system in which analytes with pI values within the formed pH gradient are focused and become immobile. Addition of formic acid to the catholyte results in the formation of an isotachophoretic zone structure that migrates toward the cathode. With ammonium hydroxide added to the anolyte migration occurs toward the anode. In the two cases, all carrier components and amphoteric analytes migrate isotachophoretically as cations or anions, respectively. The data reveal that millimolar amounts of a counter ion are sufficient to convert an IEF pattern into an ITP system. With increasing amounts of the added counter ion, the overall length of the migrating zone structure shrinks, the range of the pH gradient changes, and the migration rate increases. The studied examples indicate that systems of this type reported in the literature should be classified as ITP and not IEF. When both electrolytes are titrated, a non‐uniform background electrolyte composed of formic acid and ammonium hydroxide is established in which analytes migrate according to local pH and conductivity without forming IEF or ITP zone structures. Simulation data are in qualitative agreement with previously published experimental data.
Diagnosis of Alzheimer's disease and behavioural variant frontotemporal dementia with machine learning‐aided neuropsychological assessment using feature engineering and genetic algorithms
Authors: Garcia‐Gutierrez Fernando , Delgado‐Alvarez Alfonso , Delgado‐Alonso Cristina , Díaz‐Álvarez Josefa , Pytel Vanesa , Valles‐Salgado Maria , Gil María Jose , Hernández‐Lorenzo Laura , Matías‐Guiu Jorge , Ayala José L. , Matias‐Guiu Jordi A.
Published: December 2021

Background

Neuropsychological assessment is considered a valid tool in the diagnosis of neurodegenerative disorders. However, there is an important overlap in cognitive profiles between Alzheimer's disease (AD) and behavioural variant frontotemporal dementia (bvFTD), and the usefulness in diagnosis is uncertain. We aimed to develop machine learning‐based models for the diagnosis using cognitive tests.

Methods

Three hundred and twenty‐nine participants (170 AD, 72 bvFTD, 87 healthy control [HC]) were enrolled. Evolutionary algorithms, inspired by the process of natural selection, were applied for both mono‐objective and multi‐objective classification and feature selection. Classical algorithms (NativeBayes, Support Vector Machines, among others) were also used, and a meta‐model strategy.

Results

Accuracies for the diagnosis of AD, bvFTD and the differential diagnosis between them were higher than 84%. Algorithms were able to significantly reduce the number of tests and scores needed. Free and Cued Selective Reminding Test, verbal fluency and Addenbrooke's Cognitive Examination were amongst the most meaningful tests.

Conclusions

Our study found high levels of accuracy for diagnosis using exclusively neuropsychological tests, which supports the usefulness of cognitive assessment in diagnosis. Machine learning may have a role in improving the interpretation and test selection.
Aiming for Functional Cure With Established and Novel Therapies for Chronic Hepatitis B
Authors: Choi Hannah S.J. , Tonthat Alexander , Janssen Harry L.A. , Terrault Norah A.
Published: December 2021

Chronic hepatitis B virus (HBV) infection remains difficult to cure due to the persistent, self‐replenishing nature of the viral genome and impaired host immune responses. Current treatment goals for chronic hepatitis B (CHB) are to prevent or significantly delay liver‐related adverse outcomes and death, and two types of treatments are available: nucleos(t)ide analogues (NAs) and interferons (IFNs). NAs effectively suppress HBV replication, and IFNs improve serological response rates, thereby decreasing the risk of adverse outcomes. However, their efficacy in attaining serological responses, especially functional cure (i.e., loss of serum hepatitis B surface antigen), is very limited. Various strategies such as stopping antiviral therapy or combining therapies have been investigated to enhance response, but efficacy is only modestly improved. Importantly, the development of novel direct‐acting antivirals and immunomodulators is underway to improve treatment efficacy and enhance rates of functional cure. The present review provides an overview of the treatment goals and indications, the possibility of expanding indications, and the safety and efficacy of different treatment strategies involving established and/or novel therapies as we continue our search for a cure.
Pathological categorization of lung carcinoma from multimodality images using convolutional neural networks
Authors: Jacob Chinnu , Menon Gopakumar Chandrasekhara
Published: December 2021

Accurate diagnosis and treatment of lung carcinoma depend on its pathological type and staging. Normally, pathological analysis is performed either by needle biopsy or surgery. Therefore, a noninvasive method to detect pathological types would be a good alternative. Hence, this work aims at categorizing different types of lung cancer from multimodality images. The proposed approach involves two stages. Initially, a Blind/Referenceless Image Spatial Quality Evaluator‐based approach is adopted to extract the slices having lung abnormalities from the dataset. The slices then are transferred to a novel shallow convolutional neural network model to detect adenocarcinoma, squamous cell carcinoma, and small cell carcinoma from multimodality images. The classifier efficacy is then investigated by comparing precision, recall, area under curve, and accuracy with pretrained models and existing methods. The results narrate that the suggested system outperformed with a testing accuracy of 95% in Positron emission tomography/computed tomography (PET/CT), 93% in CT images of the Lung‐PET‐CT‐DX dataset, and 98% in the Lung3 dataset. Furthermore, a kappa score of 0.92 in PET/CT of Lung‐PETCT‐DX and 0.98 in CT of Lung3 exhibited the effectiveness of the presented system in the field of lung cancer classification.
Enabling fast path delay measurement using closeness centrality
Authors: Yan Binghao , Liu Qinrang , Shen Jianliang , Dong Liang
Published: December 2021

As one of the key performance metrics, path delay is of great significance for network policy making. Existing work has focused too much on the accuracy of delay measurement and neglected its timeliness. In response, in this paper, we propose a fast path delay measurement scheme using closeness centrality for software‐defined network. First, the node ranking method using closeness centrality is used to select the initial point for the delay measurement to enable fast forwarding of probe packets. On this basis, we assign link weights according to the delay measurement results, and readjust the measurement points to optimize the performance. A series of simulation experiments on different topologies and network state verifies the advantage of the proposed scheme in this paper in terms of time overhead for delay measurement, compared to existing work.
Pharmacists' role in buprenorphine management for opioid use disorder: A narrative review
Authors: Cleary Jacqueline , Engle Amanda , Winans Amanda
Published: December 2021

The continued rise in patients treated for opioid use disorder (OUD) has called for an increase in access to OUD therapies. Pharmacists, who have previously demonstrated their value in various disease states, have begun to address gaps in OUD care by facilitating buprenorphine treatment. The objective was to review current literature and characterize the pharmacists' role in buprenorphine collaborative care models for patients with OUD. PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, and Google Scholar were queried through May 2021. Studies were included if a pharmacist was part of a care model in which buprenorphine was prescribed for OUD and excluded if there was a pain management indication, a limited pharmacist role, or a survey methodology was used. Eight care models were included in this review. Key characteristics identified were (1) pharmacist role, (2) collaborating prescriber type, (3) clinic setting, (4) pharmacist practice type, and (5) outcomes. All models were located within a variety of outpatient settings. No collaborative practice model involved autonomous buprenorphine prescriptive authority by pharmacists. The majority utilized a psychiatrist as a collaborating prescriber, alongside a psychiatry‐trained pharmacist. Less than half utilized pharmacists to make dosing recommendations. Outcomes evaluating treatment retention and relapse rates were most reported. Most outcomes identified across each model were either improved or unchanged by pharmacist involvement. Pharmacists are valued members of buprenorphine care teams across a variety of settings, collaborate with various clinicians, and have a positive impact on patient outcomes such as treatment retention and relapse. Few published collaborative care models exist, suggesting pharmacists may be underutilized in caring for this growing patient population. The role of the pharmacist in buprenorphine management is not currently well‐defined; however, pharmacists are well prepared to take a more active role to help address the opioid crisis.
Effects of the intranasal application of gold nanoparticles on the pulmonary tissue after acute exposure to industrial cigarette smoke
Authors: Porto Germano Duarte , Haupenthal Daniela Pacheco dos Santos , Souza Priscila Soares , Silveira Gustavo de Bem , Nesi Renata Tiscoski , Feuser Paulo Emilio , Possato Jonathann Corrêa , de Andrade Vanessa Moraes , Pinho Ricardo Aurino , Silveira Paulo Cesar Lock
Published: December 2021

Inhalation of harmful particles appears as a primary factor for the onset and establishment of chronic obstructive pulmonary disease (COPD). Cigarette smoke acutely promotes an exacerbated inflammatory response with oxidative stress induction with DNA damage. Administration of Gold Nanoparticles (GNPs) with 20 nm in different concentrations can revert damages caused by external aggravations. The effects of GNPs in a COPD process have not been observed until now. The objective of this work was to evaluate the therapeutic effects of intranasal administration of different doses of GNPs after acute exposure to industrial cigarette smoke. Thirty male Swiss mice were randomly divided into five groups: Sham; cigarette smoke (CS); CS + GNPs 2.5 mg/L; CS + GNPs 7.5 mg/L and CS + GNPs 22.5 mg/L. The animals were exposed to the commercial cigarette with filter in an acrylic inhalation chamber and treated with intranasal GNPs for five consecutive days. The results demonstrate that exposure to CS causes an increase in inflammatory cytokines, histological changes, oxidative and nitrosive damage in the lung, as well as increased damage to the DNA of liver cells, blood plasma and lung. Among the three doses of GNPs (2.5, 7.5, and 22.5 mg/L) used, the highest dose had better anti‐inflammatory effects. However, GNPs at a dose of 7.5 mg/L showed better efficacies in reducing ROS formation, alveolar diameter, and the number of inflammatory cells in histology, in addition to significantly reduced rate of DNA damage in lung cells without additional systemic genotoxicity already caused by cigarette smoke.
Computational study on noncovalent interactions between (n, n) single‐walled carbon nanotubes and simple lignin model‐compounds
Authors: Badorrek Jan , Walter Michael
Published: December 2021

Composites of carbon nanotubes (CNTs) and lignin are promising and potentially cheap precursors of—to this day—expensive carbon fibers. Since the control of the CNT‐lignin interface is crucial to maximize fiber performance, it is imperative to understand the fundamental noncovalent interactions between lignin and CNT. In the present study a density functional theory study is conducted to investigate the fundamental noncovalent interaction strength between metallic (n, n) single‐walled CNT (SWCNT) and simple lignin model molecules. In particular, the respective adsorption energies are used to gauge the strength of interaction classes (ππ interaction, CHπ hydrogen bonding and OH‐related hydrogen bonding. From the data, substituent‐dependent interaction trends as well as class‐ and curvature‐dependent interaction trends are derived. Overall, we find that most of the interaction strength trends appear to be strongly influenced by geometry: flat orientation of the test molecules relative to the (n, n) SWCNT surface and small (n, n) SWCNT curvature—that is, large diameter enhances the CHπ and ππ interactions.
Development of a novel five‐lncRNA prognostic signature for predicting overall survival in elderly patients with breast cancer
Authors: Luo Yang , Zhang Yue , Wu Yu‐Xin , Li Han‐Bing , Shen Di , Che Yi‐Qun
Published: December 2021

Background

Breast cancer (BC) is an age‐related disease. Long noncoding RNAs (lncRNAs) have been proven to be crucial contributors in tumorigenesis. This study aims to develop a novel lncRNA‐based signature to predict elderly BC patients’ prognosis.

Methods

The RNA expression profiles and corresponding clinical information of 182 elderly BC patients were retrieved from The Cancer Genome Atlas (TCGA). Differentially expressed lncRNAs (DElncRNAs) between BC and adjacent normal samples were used to construct the signature in the training set through univariate Cox regression analysis, LASSO regression analysis, and multivariate Cox regression analysis. Kaplan–Meier analysis and time‐dependent receiver operating characteristic (ROC) analysis were used to evaluate the predictive performance. Besides, we developed the nomogram. Gene set enrichment analysis (GSEA) was performed to reveal the underlying molecular mechanisms.

Results

We constructed the five‐lncRNA signature (including LEF1‐AS1, MEF2C‐AS1, ST8SIA6‐AS1, LINC01224, and LINC02408) in the training set, which successfully divided the patients into low‐ and high‐risk groups with significantly different prognosis (p = 0.000049), and the AUC at 3 and 5 years of the signature was 0.779 and 0.788, respectively. The predictive performance of this signature was validated in the test and entire set. The 5‐lncRNA signature was an independent prognostic factor of OS (p = 0.007) and the nomogram constructed by independent prognostic factors was an accurate predictor of predicting overall survival probability. Besides, several pathways associated with tumorigenesis have been identified by GSEA.

Conclusions

The 5‐lncRNA signature and nomogram are reliable in predicting elderly BC patients’ prognosis and provide clues for clinical decision‐making.
Molecular structure, expression, and the emerging role of Siglec‐15 in skeletal biology and cancer
Authors: Rashid Sarah , Song Dezhi , Yuan Jinbo , Mullin Benjamin H. , Xu Jiake
Published: December 2021

Siglec‐15, a Siglec family member and type‐1 transmembrane protein, is expressed mainly in human macrophages and dendritic cells. It is comprised of a lysine‐containing transmembrane domain, two extracellular immunoglobulin (Ig)‐like domains and a short cytoplasmic domain. Siglec‐15 is highly conserved in vertebrates and acts as an immunoreceptor. It exerts diverse functions on osteoclast physiology as well as the tumor microenvironment. Siglec‐15 interacts with adapter protein DAP12 ‐ Syk signaling pathway to regulate the RANKL/RANK‐mediated PI3K, AKT, and ERK signaling pathways during osteoclast formation in vitro. Consistently, the lack of the Siglec‐15 gene in mice leads to impaired osteoclast activity and osteopetrosis in vivo. In addition, Siglec‐15 is expressed by tumor‐associated macrophages (TAMs) and regulates the tumor microenvironment by activating the SYK/MAPK signaling pathway. Interestingly, Siglec‐15 shares sequence homology to programmed death‐ligand 1 (PD‐L1) and has a potential immune‐regulatory role in cancer immunology. Thus, Siglec‐15 might also represent an alternative target for the treatment of cancers that do not respond to anti‐PD‐L1/PD‐1 immunotherapy. Understanding the role of Siglec‐15 in osteoclastogenesis and the tumor microenvironment will help us to develop new treatments for bone disorders and cancer.