bluuebunny/crossref_metadata_2025 huggingface dataset:
A Study of the Activity of Adamantyl Amines against Mutant Influenza A M2 Channels Identified a Polycyclic Cage Amine Triple Blocker, Explored by Molecular Dynamics Simulations and Solid‐State NMR**
Authors: Stampolaki Μarianna , Hoffmann Anja , Tekwani Kumar , Georgiou Kyriakos , Tzitzoglaki Christina , Ma Chunlong , Becker Stefan , Schmerer Patrick , Döring Kristin , Stylianakis Ioannis , Turcu Andreea L. , Wang Jun , Vázquez Santiago , Andreas Loren B. , Schmidtke Michaela , Kolocouris Antonios
Published: June 2023

We compared the anti‐influenza potencies of 57 adamantyl amines and analogs against influenza A virus with serine‐31 M2 proton channel, usually termed as WT M2 channel, which is amantadine sensitive. We also tested a subset of these compounds against viruses with the amantadine‐resistant L26F, V27A, A30T, G34E M2 mutant channels. Four compounds inhibited WT M2 virus in vitro with mid‐nanomolar potency, with 27 compounds showing sub‐micromolar to low micromolar potency. Several compounds inhibited L26F M2 virus in vitro with sub‐micromolar to low micromolar potency, but only three compounds blocked L26F M2‐mediated proton current as determined by electrophysiology (EP). One compound was found to be a triple blocker of WT, L26F, V27A M2 channels by EP assays, but did not inhibit V27A M2 virus in vitro, and one compound inhibited WT, L26F, V27A M2 in vitro without blocking V27A M2 channel. One compound blocked only L26F M2 channel by EP, but did not inhibit virus replication. The triple blocker compound is as long as rimantadine, but could bind and block V27A M2 channel due to its larger girth as revealed by molecular dynamics simulations, while MAS NMR informed on the interaction of the compound with M2(18–60) WT or L26F or V27A.
Top advances of the year: Genitourinary cancer
Authors: Jackson‐Spence Francesca , Young Matthew , Sweeney Christopher , Powles Thomas
Published: June 2023

There have been significant advances in the treatment of urology cancers, with a number of practice‐changing treatments. There is now greater clarity on the role of the use of immunotherapies in renal cell carcinoma. The use of triplet combinations with immune checkpoint inhibition with anti‐vascular endothelial growth factor tyrosine kinase inhibitors in the front‐line setting for metastatic disease (COSMIC313) has been explored. The use of adjuvant therapy has been complicated by a series of negative immune therapy trials. Promising results with the HIF‐2α transcription factor inhibitor, belzutifan, alone or in combination with other agents, have been reported. Antibody drug conjugates, including enfortumab vedotin and sacituzumab govitecan, have continued to show activity in urothelial cancer with promising clinical outcomes. This has led to further exploration of the combination of these novel agents with immunotherapy and accelerated Food and Drug Administration approvals. Data are also discussed regarding intensification for front‐line therapy of metastatic castrate sensitive prostate cancer. The combination of androgen‐signaling inhibitors, docetaxel, and androgen deprivation therapy (PEACE‐1, ARASENS), as well as the use of abiraterone acetate for adjuvant therapy in high‐risk disease (STAMPEDE), is included. There is also growing evidence for the use of the radioligand therapy 177Lu‐PSMA‐617 in metastatic castrate resistant disease, with an established overall survival benefit in this patient population (VISION, TheraP).

Plain Language Summary

There have been many advancements in the treatment of cancers of the kidney, bladder, and prostate in the past year.

Several studies using new therapies or new combinations of therapies have improved the chances of patients living longer with these cancers, especially those with advanced disease.

Here, we discuss a selection of the most compelling recently published data that have changed the way these cancers are treated, as well as those that are expected to change treatment in the near future.
Parents’ and adolescents’ perspectives and understanding of information about childhood cancer precision medicine
Authors: Gereis Jessica M. , Hetherington Kate , Robertson Eden G. , Daly Rebecca , Donoghoe Mark W. , Ziegler David S. , Marshall Glenn M. , Lau Loretta M. S. , Marron Jonathan M. , Wakefield Claire E.
Published: June 2023

Background

Precision medicine is projected to become integral to childhood cancer care. As such, it is essential to support families to understand what precision medicine entails.

Methods

A total of 182 parents and 23 adolescent patients participating in Precision Medicine for Children with Cancer (PRISM), an Australian precision medicine clinical trial for high‐risk childhood cancer, completed questionnaires after study enrollment (time 0 [T0]). Of the parents, 108 completed a questionnaire and 45 completed an interview following return of precision medicine results (time 1 [T1]). We analyzed the mixed‐methods data comprising measures exploring families’ perceptions and understanding of PRISM’s participant information sheet and consent form (PISCF), and factors associated with understanding.

Results

Most parents were satisfied with the PISCF, rating it as at least “somewhat” clearly presented (n = 160/175; 91%) and informative (n = 158/175; 90%). Many suggested improvements including the use of clearer language and a more visually engaging format. Parents’ actual understanding of precision medicine was low on average, but scores improved between T0 and T1 (55.8/100‐60.0/100;p = .012). Parents from culturally and/or linguistically diverse backgrounds (n = 42/177; 25%) had lower actual understanding scores than those from a Western/European background whose first language was English (p = .010). There was little correlation between parents’ perceived and actual understanding scores (p = .794; Pearson correlation –0.020; 95% CI, –0.169 to 0.116). Most adolescent patients read the PISCF either “briefly” or “not at all” (70%) and had a perceived understanding score of 63.6/100 on average.

Conclusions

Our study revealed gaps in families’ understanding of childhood cancer precision medicine. We highlighted areas for potential intervention such as through targeted information resources.

Plain Language Summary

Precision medicine is projected to become part of the standard of care for children with cancer. Precision medicine aims to give the right treatment to the right patient and involves several complex techniques, many of which may be challenging to understand.

Our study analyzed questionnaire and interview data from parents and adolescent patients enrolled in an Australian precision medicine trial.

Findings revealed gaps in families’ understanding of childhood cancer precision medicine. Drawing on parents’ suggestions and the literature, we make brief recommendations about improving information provision to families, such as through targeted information resources.
Large‐scale validation study of an improved semiautonomous urine cytology assessment tool: AutoParis‐X
Authors: Levy Joshua J. , Chan Natt , Marotti Jonathan D. , Kerr Darcy A. , Gutmann Edward J. , Glass Ryan E. , Dodge Caroline P. , Suriawinata Arief A. , Christensen Brock C. , Liu Xiaoying , Vaickus Louis J.
Published: June 2023

Background

Adopting a computational approach for the assessment of urine cytology specimens has the potential to improve the efficiency, accuracy, and reliability of bladder cancer screening, which has heretofore relied on semisubjective manual assessment methods. As rigorous, quantitative criteria and guidelines have been introduced for improving screening practices (e.g., The Paris System for Reporting Urinary Cytology), algorithms to emulate semiautonomous diagnostic decision‐making have lagged behind, in part because of the complex and nuanced nature of urine cytology reporting.

Methods

In this study, the authors report on the development and large‐scale validation of a deep‐learning tool, AutoParis‐X, which can facilitate rapid, semiautonomous examination of urine cytology specimens.

Results

The results of this large‐scale, retrospective validation study indicate that AutoParis‐X can accurately determine urothelial cell atypia and aggregate a wide variety of cell‐related and cluster‐related information across a slide to yield an atypia burden score, which correlates closely with overall specimen atypia and is predictive of Paris system diagnostic categories. Importantly, this approach accounts for challenges associated with the assessment of overlapping cell cluster borders, which improve the ability to predict specimen atypia and accurately estimate the nuclear‐to‐cytoplasm ratio for cells in these clusters.

Conclusions

The authors developed a publicly available, open‐source, interactive web application that features a simple, easy‐to‐use display for examining urine cytology whole‐slide images and determining the level of atypia in specific cells, flagging the most abnormal cells for pathologist review. The accuracy of AutoParis‐X (and other semiautomated digital pathology systems) indicates that these technologies are approaching clinical readiness and necessitates full evaluation of these algorithms in head‐to‐head clinical trials.
Compressible Navier‐Stokes equations with ripped density
Authors: Danchin Raphaël , Mucha Piotr BogusŁaw
Published: June 2023

We are concerned with the Cauchy problem for the two‐dimensional compressible Navier‐Stokes equations  supplemented with general H1 initial velocity and bounded initial density not necessarily strictly positive: it may be the characteristic function of any set, for instance. In the perfect gas case, we establish global‐in‐time existence and uniqueness, provided the volume (bulk) viscosity coefficient is large enough. For more general pressure laws (like e.g., with ), we still get global existence, but uniqueness remains an open question. As a by‐product of our results, we give a rigorous justification of the convergence to the inhomogeneous incompressible Navier‐Stokes equations when the bulk viscosity tends to infinity. In the three‐dimensional case, similar results are proved for short time without restriction on the viscosity, and for large time if the initial velocity field is small enough.
Valence Fluctuation of Uranium Ions in Uranium Sesquinitride Revealed by Dynamical Mean‐field Theory Merged with Density Functional Theory
Authors: Li Ru‐song , He Yu‐song , Cao Ze‐lin , Liu Zhi‐yong , Wang Yuan‐ming , Li Sheng , Xie Zheng
Published: June 2023

The electronic properties, in particular, the occupation number of 5f electrons and the valence state of U ions in uranium sesquinitride (U2N3) are studied by using density functional theory (DFT) calculations merged with dynamical mean‐field theory (DMFT). The results demonstrate that j=5/2 and j=7/2 manifolds are in the weakly correlated metallic and weakly correlated insulating regimes, respectively. The quasi‐particle weights indicate that LS coupling scheme is more feasible for 5f electrons, which are not in the orbital‐selective localized state. The weighted summation of the occupation probabilities of 5fn (n=0,1,2,3,4) atomic configurations suggests that 5f electrons have the inter‐configuration fluctuation, or the mixed‐valence state for U ions, together with an average occupation number of 5f electrons n5f∼2.234, which is in good agreement with the electron localization function (ELF) and occupation analysis based on other DFT‐based calculations. The 5fn‐mixing‐driven inter‐configuration fluctuation might originate from the dual nature of 5f electrons, and the flexible electronic configuration of U ions. Finally, the so‐called quasiparticle band structure is also discussed.
Assessing the fertilizer and pesticide input needs of cool‐season turfgrass species
Authors: Braun Ross C. , Watkins Eric , Hollman Andrew B. , Patton Aaron J.
Published: June 2023

Professional turfgrass managers and consumers continue to express interest in low‐input turfgrasses; however, the potential reductions in maintenance inputs from “low‐input” turfgrasses are largely assumed and have not been well‐quantified. Over 3 years, replicated field experiments at Purdue University and the University of Minnesota quantified the performance and the amount of fertilizer and pesticide inputs of cool‐season turfgrass species when managed as variable‐input turfgrass systems. Fifteen turfgrass cultivars including eight cultivars across five taxa of fine fescue (Festuca spp.), two cultivars of tall fescue (Festuca arundinacea), four cultivars of Kentucky bluegrass (Poa pratensis), and one perennial ryegrass (Lolium perenne) cultivar were investigated. Cultivars were selected to represent advances in breeding efforts. Plots received no irrigation after establishment and individual plots only received fertilizer or pesticide inputs from 2019 to 2021 if the turf in the plot exceeded or fell below a set threshold (i.e., too many pests or too low turf density). Monthly data collection and fertilizer and pesticide inputs were recorded for 3 years at each site. New fine fescue taxa cultivars provided consistently higher turf quality at both sites and required an average 56% and 41% fewer fertilizer and pesticide inputs than traditional species (tall fescue, Kentucky bluegrass, and perennial ryegrass) in Indiana and Minnesota, respectively. Compared to traditional species, older Festuca rubra ssp. cultivars reduced fertilizer and pesticide inputs by an average of 37% and 25% in Indiana and Minnesota, respectively. Fine fescue taxa, especially new cultivars, are good choices to reduce inputs and provide high turf quality for low‐input turfgrass systems.
Using perennial groundcover crops to suppress weeds and thrips in the southeast cotton belt
Authors: Billman Eric D. , Campbell Benjamin T. , Reay‐Jones Francis P. F.
Published: June 2023

Modern cotton production (Gossypium hirsutum L.) in the United States relies on chemical and physical inputs that increase the environmental and monetary costs of managing the crop. Perennial groundcover crops (PGCC) may reduce inputs by persisting in the interrow spaces of the cotton crop during summer months. A 2‐year field study was conducted in Florence, SC, to evaluate growing PGCCs with cotton using a 4 × 4 Latin square consisting of four cover crop treatments: (1) a fallow, unplanted control, (2) annual ryegrass (Lolium multiflorum Lam.) monoculture, (3) a binary red clover (Trifolium pratense L.) and white clover (Trifolium repens L.) mixture, and (4) a trinary mixture of annual ryegrass, red clover, and white clover. Fallow and annual ryegrass treatments were killed with a burndown herbicide application, while treatments containing clovers were mowed. Plots were strip‐tilled and planted with cotton in May each year. Interrow biomass, weed and thrips populations, and perennial clover populations were collected from June to October along with annual lint yields from cotton harvest in October. Results indicated that interrow biomass (2000–3000 kg ha−1), weeds (20 weeds m−2), and thrips (five thrips per five plants−1) populations were lowest in treatments containing perennial clovers, but drought and heat stress reduced clover stands within two growing seasons. Lint yield was not affected by incorporating perennial clovers into the interrow spaces of the crop. Perennial groundcover crops may provide an effective alternative to chemical weed control in cotton, but necessitate management changes to be viable in the southeastern United States.
The role of training in implementing corporate sustainability: A systematic literature review
Authors: Sult Anike , Wobst Janice , Lueg Rainer
Published: June 2023

Our literature review synthesizes the ways in which training (of management and employees) affects the implementation of corporate sustainability (CS) in organizations. We structure the research field according to the determinants of, approaches to, and outcomes of training for CS. We explain current issues in this field and develop a research agenda. We conducted a systematic literature review starting with an initial sample of 1755 empirical studies. Based on their validity, relevance, and reliability, we selected and discussed the 67 seminal sources in this field. We find that several factors foster the use of training. Besides an intrinsic organizational interest in CS, regulation and stakeholder pressure encourage organizations to prioritize training. We identify multiple approaches to and applications of training. Training on CS may be focused or multifaceted, mandated or collaboratively‐driven, but it should always be closely aligned with structure and strategic goals, and must be regularly evaluated. The literature shows that such serious and well‐designed training is linked to better environmental, social, and economic performance. Our review is the first to address the role and application of training for CS. We contribute a synthesis of empirical evidence in the field, as well as a research agenda. We highlight that practice should not see CS training from the perspectives of compliance or greenwashing, but embrace the opportunity to create a thus far underestimated alignment with strategy and long‐term performance.
Seasonality of reproduction in an ever‐wet lowland tropical forest in Amazonian Ecuador
Authors: Garwood Nancy C. , Metz Margaret R. , Queenborough Simon A. , Persson Viveca , Wright S. Joseph , Burslem David F. R. P. , Zambrano Milton , Valencia Renato
Published: June 2023

Flowering and fruiting phenology have been infrequently studied in the ever‐wet hyperdiverse lowland forests of northwestern equatorial Amazonía. These Neotropical forests are typically called aseasonal with reference to climate because they are ever‐wet, and it is often assumed they are also aseasonal with respect to phenology. The physiological limits to plant reproduction imposed by water and light availability are difficult to disentangle in seasonal forests because these variables are often temporally correlated, and both are rarely studied together, challenging our understanding of their relative importance as drivers of reproduction. Here we report on the first long‐term study (18 years) of flowering and fruiting phenology in a diverse equatorial forest, Yasuní in eastern Ecuador, and the first to include a full suite of on‐site monthly climate data. Using twice monthly censuses of 200 traps and >1000 species, we determined whether reproduction at Yasuní is seasonal at the community and species levels and analyzed the relationships between environmental variables and phenology. We also tested the hypothesis that seasonality in phenology, if present, is driven primarily by irradiance. Both the community‐ and species‐level measures demonstrated strong reproductive seasonality at Yasuní. Flowering peaked in September–November and fruiting peaked in March–April, with a strong annual signal for both phenophases. Irradiance and rainfall were also highly seasonal, even though no month on average experienced drought (a month with <100 mm rainfall). Flowering was positively correlated with current or near‐current irradiance, supporting our hypothesis that the extra energy available during the period of peak irradiance drives the seasonality of flowering at Yasuní. As Yasuní is representative of lowland ever‐wet equatorial forests of northwestern Amazonía, we expect that reproductive phenology will be strongly seasonal throughout this region.
Mortality rate after coronary revascularization in heart failure patients with coronary artery disease
Authors: Nader Vanessa , Matta Anthony , Kang Ryeonshi , Deney Antoine , Azar Rania , Rouzaud‐Laborde Charlotte , Kunduzova Oxana , Itier Romain , Fournier Pauline , Galinier Michel , Carrié Didier , Roncalli Jerome
Published: June 2023

Aims

Coronary artery disease (CAD) is a common cause of heart failure (HF). It remains unclear who, when and why to direct towards coronary revascularization. The outcomes of coronary revascularization in HF patients are still a matter of debate nowadays. This study aims to evaluate the effect of revascularization strategy on all‐cause of death in the context of ischaemic HF.

Methods and results

An observational cohort was conducted on 692 consecutive patients who underwent coronary angiography at the University Hospital of Toulouse between January 2018 and December 2021 for either a recent diagnosis of HF or a decompensated chronic HF, and in whom coronary angiograms showed at least 50% obstructive coronary lesion. The study population was divided into two groups according to the performance or not of a coronary revascularization procedure. The living status (alive or dead) of each of the study's participants was observed by April 2022. Seventy‐three per cent of the study population underwent coronary revascularization either by percutaneous coronary intervention (66.6%) or coronary artery bypass grafting (6.2%). Baseline characteristics including age, sex and cardiovascular risk factors did not differ between the invasive and conservative groups, respectively. Death occurred in 162 study participants resulting in an all‐cause mortality rate of 23.5%; 26.7% of observed deaths have occurred in the conservative group versus 22.2% in the invasive group (P = 0.208). No difference in survival outcomes has been observed over a mean follow‐up period of 2.5 years (P = 0.140) even after stratification by HF categories (P = 0.132) or revascularization modalities (P = 0.366).

Conclusions

Findings from the present study showed comparable all‐cause mortality rates between groups. Coronary revascularization does not modify short‐term survival outcomes in HF patients compared with optimal medical therapy alone outside the setting of acute coronary syndrome.
Global longitudinal strain predicts clinical outcomes in patients with heart failure with preserved ejection fraction
Authors: Brann Alison , Miller James , Eshraghian Emily , Park Jin Joo , Greenberg Barry
Published: June 2023

Aims

Patients with heart failure with preserved ejection fraction (HFpEF) are at high risk for hospitalization and mortality and many of these patients experience a deterioration in left ventricular ejection fraction (LVEF) over time. Global longitudinal strain (GLS) is a sensitive marker of myocardial dysfunction that could help predict risk for future events in this population. We assessed whether GLS can predict adverse clinical outcomes and future deterioration in LVEF in patients with HFpEF.

Methods and results

In this retrospective cohort study, patients with HFpEF were divided into groups according to abnormal GLS (>−15.8%) or normal GLS (<−15.8%).The primary outcomes were: a composite of cardiovascular mortality or heart failure hospitalization and deterioration in LVEF to <40%. Among the 311 patients with HFpEF, 128 patients (41%) had normal GLS and 183 patients (59%) had abnormal GLS. After a median follow‐up of 4.6 years, the composite outcome occurred more commonly in patients with abnormal GLS compared to patients with normal GLS (62% vs. 44%; hazard ratio [HR] 1.74, 95% confidence interval [CI] 1.3–2.4, p < 0.001). Patients with abnormal GLS were also more likely to experience a deterioration in LVEF (19% vs. 10%; HR 2.2, 95% CI 1.2–4.3, p = 0.018). When assessed as a continuous variable, each 1% increase in GLS was associated with 10% increased odds for the composite outcome and 13% increased odds for deterioration in LVEF.

Conclusion

In patients with HFpEF, abnormal GLS is common and is a strong predictor for clinical events and future deterioration in LVEF.
Chiral‐at‐Molybdenum – A Computational Study on N‐Substituted cis‐MoO2(nacnac)2
Authors: Dhimba George , Muller Alfred , Lammertsma Koop
Published: June 2023

Cis‐MoO2(nacnac)2 (nacnac=β‐diketiminate) can be a viable chiral‐at‐metal catalyst when its two β‐diketiminate (nacnac) ligands are N‐substituted to prevent Λ⇌Δ racemization. Even simple methyl groups raise the barriers for racemization significantly for the Bailar, Rây‐Dutt, Conte‐Hippler, and Dhimba‐Muller‐Lammertsma (DML) twists to a respectable 28.5, 37.8, 30.5, and 25.1 kcal/mol, respectively, at ωB97X‐D/6‐311+G(2d,p) (LANL2DZ for Mo) including acetonitrile solvation. The lowest energy DML barrier increases to ΔGo=27.4 kcal/mol with N‐substituted t‐butyl groups. The nacnac ligands’ electronic and steric components to the racemization barriers are discussed.
Determination of acidity constants of pyridines, imidazoles, and oximes by capillary electrophoresis
Authors: Hajduk Anna , Ulrich Nadin
Published: June 2023

The acidity constant in the form of pKa is one of the most important physicochemical quantities. There are prediction tools available for calculating the pKa, but they only deliver precise calculated values for a relatively small set of chemicals. For complex structures with multiple functional groups in particular, the error in the predicted pKa is high due to the application domain of the corresponding models. Thus, we aim to enlarge the dataset of experimentally determined pKa values using capillary electrophoresis. We, therefore, selected various pyridines, imidazoles, and oximes to determine the pKa values using the internal standard approach and the classical method. Especially oximes were not investigated in the past, and predictions for them include larger errors. Thus, our experimentally determined values could contribute to an improved understanding of various functional groups impacting the pKa values and serve as additional datasets to develop improved pKa prediction tools.
Fault Diagnosis and Fault‐Tolerant Control Method for a Multistack Fuel Cell Thermal Management Subsystem
Authors: Zhou Su , Gao Jianhua , Pan Zhirong , Zhang Gang , Zhai Shuang , Shen Wei
Published: June 2023

Multistack fuel cell systems (MFCS) are promising developments of fuel cell technology. For MFCS, faults affect durability and stability, and appropriate fault diagnosis methods and control strategies need to be proposed for different multistack structures. Herein, the integrated MFCS thermal management subsystem (TMS), which is based on the optimized split‐stack approach, is first studied, and its possible sensor and actuator faults are analyzed. The sensor fault signal is corrected based on the unscented Kalman filter (UKF), the controller design under the hardware in the loop platform is carried out, and an active fault‐tolerant control (FTC) strategy based on sliding mode control is deployed for the TMS to enable it to recover its performance quickly and effectively in case of faults. The results show that the estimated values are closer to the true values after using the UKF on the sensor signals, avoiding the impact of sensor faults on the system performance. Under New European Driving Cycle dynamic conditions, the FTC controller also exhibits better control compared to the conventional proportional–integral controller, with smaller maximum overshoot and shorter system recovery and stabilization time in the event of a TMS fault, mitigating the impact of system fault on performance.
Enhancing Electrochemical Performance in PEO/LLZTO Composite Solid Electrolyte via PEG Polymer Integration for Solid‐State Batteries
Authors: Song Young-Woong , Park Sang-Jun , Heo Kookjin , Lee Hyochan , Hwang Dahee , Kim Min-Young , Kim Jaekook , Lim Jinsub
Published: June 2023

Composite solid electrolytes (CSE) are promising candidate materials that can complement the ionic conductivity and thermal and electrochemical stabilities of solid polymer electrolytes. In this study, the ionic conductivity, Li migration characteristics, and electrochemical stability are investigated of “polymer‐in‐ceramic”‐structured CSE sheet into which polyethylene glycol polymer is introduced. PEG10 CSE exhibits ionic conductivity twice as high as PEG0 CSE at 50 °C and shows high oxidation potential stability of 5.2 V. In addition, PEG10 CSE has high interfacial compatibility with Li metal, and LiFePO4/PEG10 CSE/Li cell evaluation confirms that PEG10 CSE has high discharge capacity, C‐rate performance, and cycle stability at 45 °C.
Simultaneous Network Reconfiguration and Wind Power Plants Participation in Day‐Ahead Electricity Market Considering Uncertainties
Authors: Naghizadeh Kouchesfahani Reza , Mohtavipour Seyed Saeid , Mojallali Hamed
Published: June 2023

Recently, the participation of wind sources in electricity markets has become a severe challenge due to their intermittent nature. Reconfiguration of power systems can effectively reduce the negative effects of uncertainties. So, this article presents a new method for participating in wind power plants and uncertain customers in a day‐ahead electricity market considering the reconfiguration process. This method tries to maximize social welfare through a two‐level optimization problem. To this end, uncertainties are modeled using the empirical cumulative distribution function and the Monte–Carlo method, and a probabilistic analysis of the market is performed. Then, by defining some indices to evaluate the participants’ satisfaction and using the analytic hierarchy process method (AHP), a new objective function is proposed so that its minimization leads to planning the system configuration and market participants to optimize mentioned indices. The proposed methodology also assumes that the participation of uncertain participants in the spot market will eliminate the imbalances caused by uncertainties. The simulations are implemented using real data on an 8‐bus sample network. The results confirm the efficiency of the proposed method in significantly reducing power producers’ and customers’ costs along with increasing total income and profit from the sale of energy.
Cultivation of aerobic granular biomass in continuous flow‐intermittent decant type reactor fed with anaerobic effluent
Authors: Rayaz Mohd , Khatoon Fehmeeda , Khan Abid Ali
Published: June 2023

This study aimed to investigate the feasible operating conditions for the formation of aerobic granular biomass (AGB) in a continuous flow‐intermittent decant (CFID) type reactor. During the start‐up phase, that is, the operational period – I, the reactor was fed with sewage, and aerobic granules began to grow after 20 days of reactor start‐up. In period – II, experiments were conducted with 50% sewage and 50% anaerobic effluent (i.e., UASB‐treated effluent) as substrates, and subsequently, upon successful formation of mature granules, anaerobic effluent was added throughout operational periods III and IV. Results inferred that the highest removal of COD, NH4+N, TN, and PO43−P was observed in the study periods III and IV, with removal rates of 75.2 ± 10.97%, 79.24 ± 14.81%, 67.66 ± 7.17%, and 47.12 ± 14.69%, respectively. The particle size analysis shows the size of the granules was significantly increased in period IV of the study compared to previous study phases. The scanning electron microscopy (SEM) images referred that rod‐shaped bacteria were abundant after period I, while enriched microbial species of coccus, bacillus, and filamentous fungus were observed at the end of the study. These findings suggest that CFID‐type reactor can effectively cultivate AGB and remove organics and nutrients from anaerobic effluent.
Collaborative filtering‐based collapse fragility assessment
Authors: Guan Xingquan , Burton Henry V.
Published: June 2023

This paper presents a computationally efficient collapse fragility assessment approach that leverages the collaborative filtering (CF) technique. The proposed method randomly selects and runs a subset of the nonlinear response history analyses (NRHAs) required for the incremental dynamic analysis. The structural performance in the omitted cases is then estimated using CF, which requires significantly less time and effort than the nonlinear structural analysis. The NRHA‐based and CF‐generated building performances are then assembled to determine the empirical probability of collapse at each intensity, which is later fitted with a lognormal distribution to obtain the median collapse capacity and associated dispersion. The proposed approach is applied to three steel moment frames, demonstrating that it can reduce the required NRHAs by 50% while providing a reliable collapse fragility estimate for the selected ground motion sets (FEMA P695 44 far‐field records and a site‐specific record‐set). The results from sensitivity analyses reveal that the proposed method is reasonably robust unless the input parameters are assigned extreme values.
Room‐Temperature Alkyl‐Diphenylpyrene Liquefication by Molecular Desymmetrization
Authors: Lu Fengniu , Shinohara Akira , Kawamura Izuru , Saeki Akinori , Takaya Tomohisa , Iwata Koichi , Nakanishi Takashi
Published: June 2023

Achieving the lowest phase transition temperature with minimal chemical modification in highly crystalline π‐conjugated molecules is a universal problem in related research fields. This paper reports room‐temperature liquefication of diphenylpyrene isomers by introducing bulky yet flexible branched alkyl chains through molecular desymmetrization. Six isomers with different symmetries depending on the positions of the phenyl groups and alkyl groups were synthesized, and three of the isomers were found to be liquids at 25 °C, a state in which they have remained for more than five years. Although it is generally believed that the lower the symmetry of a molecule, the less likely it is to crystallize, one molecule with a relatively high molecular symmetry unexpectedly did not crystallize, which was evidenced by the kinetic inhomogeneity of this amorphous material (practically stable liquid) assessed by rheological analysis.
Prevalence and clinical impact of anemia in patients diagnosed with chronic obstructive pulmonary disease: A cross‐sectional study
Authors: Rimal Suman , Das Santa K. , Basnet Anita , Rauniyar Tej P. , Pandey Kundan Raj , Kuikel Sandip
Published: June 2023

Background and Aims

Unlike classically described polycythemia, anemia is found to be more prevalent in patients with chronic obstructive pulmonary disease (COPD). Anemia increases the cost of hospital stay and causes an increased risk of adverse outcomes including death in COPD patients. This study was done to find the prevalence of anemia in COPD patients, the factors associated, and the outcomes of anemic COPD.

Methods

It was a quantitative, descriptive‐analytical, and cross‐sectional study conducted in Tribhuvan University Teaching Hospital's medical wards and the Emergency Room from September 2019 to September 2020. A simple random sampling method was used. Clinical information was obtained, and patients were followed up 3 months after discharge to document the number of exacerbations and deaths if present.

Results

The patients in our study had a mean age of 70.80 ± 11.16 years. Most were female. Most (85.5%) had a history of exposure to firewood smoke. Twenty‐three percent of the patients had anemia and these patients had significantly greater mortality 3 months postdischarge. Middle‐old and old were more likely to have anemia with odds ratio (OR) of 2.55 (confidence interval [CI]: 0.48–13.5) and 13.6 (CI: 1.12–24.2), respectively. Current smokers had less likelihood of having anemia (OR: 0.05, CI: 0.006–0.49). Multivariate analysis showed that age, sex, and smoking status were significant determinants of anemia in COPD. There was no association between anemia and duration of hospital stay. However, mortality was higher at 3 months in COPD patients with anemia (p < 0.001).

Conclusion

In COPD patients, anemia is prevalent comorbidity that is significantly linked to higher mortality but not to exacerbations. It is unknown, though, if treating anemia in COPD patients will affect the patient's outcome. Additional research in this area may be possible.
Numerical modeling of two‐phase flows in the presence of dynamic and thermal interactions
Authors: Tulegenov Kubaidolla K. , Kamalova Gaukhar A. , Bekenova Anargul S. , Diyarova Lunara B.
Published: June 2023

The study of turbulent flow in mixtures consisting of gas and particulate matter is a current area of research among modern scientists. The main objective of this area is to prevent the reduction of burnout in flow‐through systems. Therefore, the purpose of this research is to develop a mathematical model of turbulent gas flow with solids to explore the structure of the combustion region in a channel with a partially open boundary to determine the interfacial interaction of the injection of a flat heterogeneous flow in a confined area and the influence of regime parameters on the ignition process. For this purpose, a modeling method was used, which involved using the fundamental laws of continuity of flow, conservation of energy, and the quantity of motion and matter, and an experiment was conducted to reconcile the proposed model with theoretical data. As a result of this work, a model based on the averaged Reynolds Navier–Stokes equations and an algorithm for solving a turbulent subsonic two‐dimensional flow in a heterogeneous medium based on an Euler–Lagrange representation have been developed. Thus, the effects of the parameters of entrainment, temperature, and component concentration on the combustion range and mixing intensity were determined. The proposed methodology can be applied to solve application problems of various kinds, for example, in the design of thermal power plants. The scope of the mathematical and numerical models developed is sufficiently broad that they are universal.
Introduction to special section doing the “right” thing: Ethical issues in infant and early childhood mental health
Authors: Zeanah Paula D. , Korfmacher Jon , Lim Izaak , Steier Alison , Zeanah Charles H.
Published: June 2023

Introducción a la Sección Especial: Hacer lo ‘correcto:’ Asuntos éticos en la salud mental infantil y en la temprana niñez

ética, salud mental infantil y en la temprana niñez, código de ética
Effectiveness of photodynamic therapy adjunct to oral debridement in improving clinical, microbiological, and pain in necrotizing ulcerative gingivitis
Authors: Al‐Kheraif Abdulaziz A. , Javed Ravish , Al‐Momani Mohammed Mahmoud , Wasi Aisha , Khan Aftab Ahmed
Published: June 2023

To evaluate the efficacy of photodynamic therapy (PDT) as adjunctive to oral debridement (OD) in the improvement of clinical, microbiological, and pain in patients with necrotizing ulcerative gingivitis (NUG). Patients with NUG were split into two groups: Group‐OD + PDT received PDT with OD, while Group‐OD underwent OD alone. Clinical inflammatory parameters including full mouth plaque scores (FMPS), full mouth bleeding scores (FMBS), and probing depth (PD) were assessed. Fusobacterium nucleatum and Prevotella intermedia were analyzed using the polymerase chain reaction technique. Pain examination was done using various pain scales. Group PDT + OD showed more reduction in FMPS, FMBS, and greater reduction in F. nucleatum and P. intermedia count compared to group OD at 12 weeks follow up (p < 0.01). Group PDT + OD showed significantly lower pain scores at 12 weeks (p < 0.05). PDT was more effective in improving clinical parameters, and reducing bacterial counts and pain in NUG patients than dental scaling alone.
Matrine suppresses liver cancer progression and the Warburg effect by regulating the circROBO1/miR‐130a‐5p/ROBO1 axis
Authors: Huang Zhengchun , Li Hongwei , Li Qihua , Chen Xuehong , Liu Ruizhen , Chang Xinfeng
Published: June 2023

Matrine, an effective component extracted from the traditional Chinese herb, Sophora flavescens, has been indicated to exert antitumor activity in different types of cancer. However, the role and precise mechanism of matrine in the progression of liver cancer remains largely unclear. Cell viability, cell proliferation, cell apoptosis, and Warburg effect were estimated by cell counting kit‐8 assay, colony formation assay, flow cytometry assay, and glucose uptake and lactate production assay, respectively. The candidate Circular RNAs (circRNAs) were screened by integrating the Gene Expression Omnibus database (GSE155949) analysis with the online program GEO2R. A quantitative real‐time polymerase chain reaction was employed to test the expression of circRNA circROBO1, microRNA miR‐130a‐5p, and roundabout homolog 1 (ROBO1). The interaction of circROBO1/miR‐130a‐5p/ROBO1 axis was predicted and confirmed by bioinformatics analysis, a dual‐luciferase reporter assay, and an RNA pull‐down assay. A xenograft mouse model was employed to reveal the role of matrine in vivo. Matrine repressed liver cancer cell viability, proliferation, and Warburg effect, but increased cell apoptosis in vitro. CircROBO1 and ROBO1 were upregulated, but miR‐130a‐5p was downregulated in liver cancer tissues. Additionally, matrine could reduce the expression of circROBO1 and ROBO1, and increase the expression of miR‐130a‐5p. Mechanically, overexpression of circROBO1 partly recovered the effect of matrine on liver cancer cell viability, proliferation, apoptosis, and Warburg effect by regulating the miR‐130a‐5p/ROBO1 axis. Matrine impeded liver cancer development by mediating the circROBO1/miR‐130a‐5p/ROBO1 axis, which provided a theoretical basis for the application of matrine as an effective anticancer drug for liver cancer.
Bacteriophages: The promising therapeutic approach for enhancing ciprofloxacin efficacy against bacterial infection
Authors: Shariati Aref , Noei Milad , Chegini Zahra
Published: June 2023

Background

The emergence of ciprofloxacin‐resistant bacteria is a serious challenge worldwide, bringing the need to find new approaches to manage this bacterium. Bacteriophages (phages) have been shown inhibitory effects against ciprofloxacin‐resistance bacteria; thus, ciprofloxacin resistance or tolerance may not affect the phage's infection ability. Additionally, researchers used phage‐ciprofloxacin combination therapy for the inhibition of multidrug‐resistant bacteria.

Results

The sublethal concentrations of ciprofloxacin could lead to an increase in progeny production. Antibiotic treatments could enhance the release of progeny phages by shortening the lytic cycle and latent period. Thus, sublethal concentrations of antibiotics combined with phages can be used for the management of bacterial infections with high antibiotic resistance. In addition, combination therapy exerts various selection pressures that can mutually decrease phage and antibiotic resistance. Moreover, phage ciprofloxacin could significantly reduce bacterial counts in the biofilm community. Immediate usage of phages after the attachment of bacteria to the surface of the flow cells, before the development of micro‐colonies, could lead to the best effect of phage therapy against bacterial biofilm. Noteworthy, phage should be used before antibiotics usage because this condition may have allowed phage replication to occur first before ciprofloxacin interrupted the bacterial DNA replication process, thereby interfering with the activity of the phages. Furthermore, the phage‐ciprofloxacin combination showed a promising result for the management of Pseudomonas aeruginosa infections in mouse models. Nevertheless, low data are existing about the interaction between phages and ciprofloxacin in combination therapies, especially regarding the emergence of phage‐resistant mutants. Additionally, there is a challenging and important question of how the combined ciprofloxacin with phages can increase antibacterial functions. Therefore, more examinations are required to support the clinical usage of phage‐ciprofloxacin combination therapy.
Use of Real‐World Evidence in a Virtual Bridging Analysis for a Human Epidermal Growth Factor Receptor 2–Targeted Antibody–Drug Conjugate in Gastric Cancer
Authors: Lu Zheng , Wada Russ , Salas Maribel , Singh Jasmeet , Kawaguchi Yoshinori , Belli Andrew J. , Abutarif Malaz , Garimella Tushar
Published: June 2023

This study bridged pharmacokinetic, efficacy, and safety clinical trial data from Japan to a Western population using real‐world evidence (RWE) to investigate the antibody–drug conjugate trastuzumab deruxtecan (T‐DXd) in the treatment of human epidermal growth factor receptor 2 (HER2)‐positive advanced gastric cancer. Using population pharmacokinetic and exposure–response (efficacy/safety) models, exposure–efficacy data from 117 patients and exposure–safety data from 158 patients in Japan who received T‐DXd 6.4 mg/kg as second‐line or later treatment were bridged to RWE including covariate information from 25 Western patients with HER2‐positive gastric cancer who received second‐line or later T‐DXd treatment. Pharmacokinetic simulations indicated that intact T‐DXd and released drug (DXd) steady‐state exposures were comparable between Western patients and patients from Japan; the Western/Japan ratio of exposure medians ranged from 0.82 (T‐DXd steady‐state minimum concentration) to 1.18 (DXd steady‐state maximum concentration). Exposure–efficacy simulations estimated a confirmed objective response rate of 28.6% (90% confidence interval, 20.8‐38.4) in real‐world Western patients versus 40.1% (90% confidence interval, 33.5‐47.0) in patients from Japan, possibly because of checkpoint inhibitor use in 4% versus 30% of patients, respectively. Western patients had a higher estimated rate of serious adverse events than patients from Japan (42.2% vs 34.6%); however, the rate of interstitial lung disease was lower (less than 10%) in Western patients. Overall, T‐DXd was predicted to have meaningful clinical activity and a manageable safety profile in Western patients with HER2‐positive gastric cancer. Using RWE, bridging analysis supported US approval of T‐DXd 6.4 mg/kg in advanced gastric cancer before a clinical trial was completed in Western patients.
Drug–Drug Interaction Potential of Mavacamten with Oral Contraceptives: Results from a Clinical Pharmacokinetic Study and a Physiologically Based Pharmacokinetic Model
Authors: Chiang Manting , Sychterz Caroline , Gaohua Lu , Perera Vidya , Gretler Daniel D. , Florea Victoria , Merali Samira
Published: June 2023

Mavacamten is a potential inducer of cytochrome P450 (CYP) 3A4 and, as such, could reduce the exposure of the active components of oral contraceptives, ethinyl estradiol (EE) and norethindrone (NOR), where CYP3A4 is involved in metabolism. This study assessed if repeat doses of mavacamten led to a drug–drug interaction with EE and/or NOR. This was an open‐label study in healthy women. In Period 1, participants received 35 mcg of EE and 1 mg of NOR. In Period 2, participants received oral loading doses of mavacamten 25 mg on Days 1–2, 15 mg/day on Days 3‒17, and 35 mcg of EE and 1 mg of NOR on Day 15. Plasma concentrations of mavacamten, EE, and NOR were obtained before dosing and up to 72 hours after dosing. For EE only, a physiologically based pharmacokinetic model was used to simulate mavacamten‐mediated CYP3A4 induction with EE for various CYP2C19 phenotypes. In total, 13 women were enrolled (mean age, 38.9 [standard deviation, 9.65] years). After mavacamten administration, modest increases in area under the concentration–time curves were observed for both EE and NOR. The maximum concentrations and half‐lives for EE and NOR were not affected by coadministration with mavacamten. Criteria for bioequivalence were met or nearly met for EE and NOR exposure with geometric mean ratios between 0.8 and 1.25. All adverse events were mild. The physiologically based pharmacokinetic model predicted a less than 15% decrease in EE exposure across CYP2C19 phenotypes. Coadministration of mavacamten at a therapeutically relevant dose with EE and NOR did not decrease the exposure to either EE or NOR to a level that may lead to reduced effectiveness.