bluuebunny/crossref_metadata_2025 huggingface dataset:
Gut microbiome in association with chemotherapy‐induced toxicities among patients with breast cancer
Authors: Nguyen Sang M. , Tran Huong T. T. , Long Jirong , Shrubsole Martha J. , Cai Hui , Yang Yaohua , Cai Qiuyin , Tran Thuan V. , Zheng Wei , Shu Xiao‐Ou
Published: February 2024

Background

Little research has focused on the relationship between gut microbiome and chemotherapy‐induced toxicity.

Methods

This prospective study involves 301 patients with breast cancer who had prechemotherapy stool samples collected. Gut microbiome was sequenced by shotgun metagenomics; associations with chemotherapy‐induced toxicities during first‐line treatment by gut microbial diversity, composition, and metabolic pathways with severe (i.e., grade ≥3) hematological and gastrointestinal toxicities were evaluated via multivariable logistic regression.

Results

High prechemotherapy α‐diversity was associated with a significantly reduced risk of both severe hematological toxicity (odds ratio [OR] = 0.94; 95% CI, 0.89–0.99; p = .048) and neutropenia (OR = 0.94; 95% CI, 0.89–0.99; p = .016). A high abundance of phylum Synergistota, class Synergistia, and order Synergistales were significantly associated with a reduced risk of severe neutropenia; conversely, enrichment of phylum Firmicutes C, class Negativicutes, phylum Firmicutes I, and class Bacilli A, order Paenibacillales were significantly associated with an increased risk of severe neutropenia (p range: 0.012–2.32 × 10–3; false discovery rate <0.1). Significant positive associations were also observed between severe nausea/vomiting and high Chao1 indexes, β‐diversity (p < .05), 20 species belonging to the family Lachnospiraceae, Oscillospiraceae, and Ruminococcaceae (p value range: 6.14 × 10–3 to 1.33 × 10–5; false discovery rate <0.1), and three metabolic pathways involved in reductive tricarboxylic acid cycle I and cycle II, and an incomplete reductive tricarboxylic acid cycle (p < .01). Conversely, a high abundance of species Odoribacter laneus and the pathway related to the L‐proline biosynthesis II were inversely associated with severe nausea/vomiting.

Conclusions

Our study suggests that gut microbiota may be a potential preventive target to reduce chemotherapy‐induced toxicity.
Pharmacokinetics and Pharmacodynamics of Etripamil, an Intranasally Administered, Fast‐Acting, Nondihydropyridine Calcium Channel Blocker
Authors: Ip James E. , Wight Douglas , Yue Corinne Seng , Nguyen David , Plat Francis , Stambler Bruce S.
Published: February 2024

Etripamil, a fast‐acting nondihydropyridine L‐type calcium channel blocker, is under investigation for potential self‐administration for the acute treatment of supraventricular tachyarrhythmias in a medically unsupervised setting. We report detailed pharmacokinetics and pharmacodynamics of intranasally administered etripamil in healthy adults from 2 Phase 1, randomized, double‐blind studies: Study MSP‐2017‐1096 (sequential dose‐escalation, crossover study design, n = 64) and NODE‐102 (single dose, 4‐way crossover study, n = 24). Validated bioanalytical assays determined plasma concentrations of etripamil and its inactive metabolite. Noncompartmental pharmacokinetic parameters were calculated. Pharmacodynamic parameters were determined for PR interval, blood pressure, and heart rate. Etripamil was rapidly absorbed intranasally, with time to maximal plasma concentration of 5‐8.5 minutes, corresponding to a rapid greater than 10% increase in mean maximum PR interval from baseline within 4‐7 minutes of doses of 60 mg or greater. Following peak plasma concentrations, systemic etripamil levels declined rapidly within the first 15 minutes following dosing and decreased more gradually thereafter. PR interval prolongation greater than 10% from baseline was generally sustained for about 45 minutes at doses of 60 mg or greater. The mean terminal half‐life ranged from about 1.5 hours with 60 mg to about 2.5‐3 hours for the 70‐ and 105‐mg doses. Etripamil was generally well tolerated without symptomatic hypotension. Adverse events were primarily mild to moderate and related to the administration site; no serious adverse events or episodes of atrioventricular block occurred. Intranasal etripamil administration, at doses of 60 mg or greater, produced rapidly occurring slowing of atrioventricular nodal conduction with a limited duration of effect without hemodynamic or electrocardiographic safety signals in healthy volunteers.
Improved Conductivity and in Situ Formed Heterojunction via Zinc Doping in CuBi2O4 for Photoelectrochemical Water Splitting
Authors: Hu Yingfei , Hu Qingyuan , Chen Xianliu , Zhao Mengting , Wang Yumeng , Guan Hangmin , Hu Xuemin , Wang Yuanyuan , Feng Jianyong
Published: February 2024

As a photocathode with a band gap of about 1.8 eV, copper bismuthate (CuBi2O4) is a promising material for photoelectrochemical (PEC) water splitting. However, weak charge transfer capability and severe carrier recombination suppress the PEC performance of CuBi2O4. In this paper, the conductivity and carriers transport of CuBi2O4 are improved via introducing Zn2+ into the synthesis precursor of CuBi2O4, driving a beneficial 110 mV positive shift of onset potential in photocurrent. Detailed investigations demonstrate that the introduction of an appropriate amount of zinc leads to in situ segregation of ZnO which serves as an electron transport channel on the surface of CuBi2O4, forming heterojunctions. The synergistic effect of heterojunctions and doping simultaneously promotes the charge transfer and the carrier concentration. OCP experiment proves that ZnO/Zn−CuBi2O4 possesses better charge separation; the Mott–Schottky curve shows that the doping of Zn significantly enhances the carrier concentration; carrier lifetime calculated from time–resolved photoluminescence confirms faster extraction of carriers.
Vibrational Circular Dichroism Spectroscopy with a Classical Polarizable Force Field: Alanine in the Gas and Condensed Phases
Authors: Bowles Jessica , Jähnigen Sascha , Agostini Federica , Vuilleumier Rodolphe , Zehnacker Anne , Calvo Florent , Clavaguéra Carine
Published: February 2024

Polarizable force fields are an essential component for the chemically accurate modeling of complex molecular systems with a significant degree of fluxionality, beyond harmonic or perturbative approximations. In this contribution we examine the performance of such an approach for the vibrational spectroscopy of the alanine amino acid, in the gas and condensed phases, from the Fourier transform of appropriate time correlation functions generated along molecular dynamics (MD) trajectories. While the infrared (IR) spectrum only requires the electric dipole moment, the vibrational circular dichroism (VCD) spectrum further requires knowledge of the magnetic dipole moment, for which we provide relevant expressions to be used with polarizable force fields. The AMOEBA force field was employed here to model alanine in the neutral and zwitterionic isolated forms, solvated by water or nitrogen, and as a crystal. Within this framework, comparison of the electric and magnetic dipole moments to those obtained with nuclear velocity perturbation theory based on density‐functional theory for the same MD trajectories are found to agree well with one another. The statistical convergence of the IR and VCD spectra is examined and found to be more demanding in the latter case. Comparisons with experimental frequencies are also provided for the condensed phases.
Copper Current Collector: The Cornerstones of Practical Lithium Metal and Anode–Free Batteries
Authors: Zhou Jinyang , Qin Jian , Zhan Hui
Published: February 2024

Comparing with the commercial Li–ion batteries, Li metal secondary batteries (LMB) exhibit unparalleled energy density. However, many issues have hindered the practical application. As an element in lithium metal and anode–free batteries, the role of current collector is critical. Comparing with the cathode current collector, more requirements have been imposed on anode current collector as the anode side is usually the starting point of thermal runaway and many other risks, additionally, the anode in Li metal battery very likely determines the cycling life of full cell. In the review, we first give a systematic introduction of copper current collector and the related issues and challenges, and then we summarize the main approaches that have been mentioned in the research, including Cu current collector with 3D architecture, lithophilic modification of the current collector, artificial SEI layer construction on Cu current collector and carbon or polymer decoration of Cu current collector. Finally, we give a prospective comment of the future development in this field.
Hydrodifluoromethylation of unactivated alkenes enabled by Visible‐Light Photocatalysis
Authors: Jha Avishek Kumar , Kumar Vivek , Perumandla Sanjay Kumar , Yatham Veera Reddy
Published: February 2024

In the present manuscript, we have reported a general catalytic strategy that allows the synthesis of a variety of difluoro methylated alkanes from the corresponding unactivated alkenes using commercially available radical difluoromethylating reagent (CF2HSO2Na) under visible light photocatalysis. Further, this strategy allows the late‐stage modification of various alkenes derived from pharmaceutically relevant drugs.
In‐situ one‐step construction of poly(heptazine imide)/poly(triazine imide) heterojunctions for photocatalytic hydrogen evolution
Authors: Li Hui , Zhang Guoqiang , Zhang Peixin , Mi Hongwei
Published: February 2024

The construction of heterojunctions is challenging, requiring atomic‐level contact and interface matching. Here, we have achieved atomic‐level interfacial matching by constructing poly(heptazine imide)/poly(triazine imide) crystalline carbon nitride heterojunctions in an in‐situ one‐step method. The content of poly(triazine imide) in heterojunctions is positively related to the proportion of lithium chloride in potassium chloride and lithium chloride mixed‐salts. The optimized heterojunction achieves an apparent quantum efficiency of 48.34 % for photocatalytic hydrogen production at 420 nm, which is at a good level in polymeric carbon nitride photocatalysts. The proposed ion‐thermal assisted heterojunction construction strategy contributes to the development of polymeric carbon nitride photocatalysts with high crystallization and high charge separation efficiency.
Spatial transcriptomics reveals heterogeneity of histological subtypes between lepidic and acinar lung adenocarcinoma
Authors: Xie Linshan , Kong Hui , Yu Jinjie , Sun Mengting , Lu Shaohua , Zhang Yong , Hu Jie , Du Fang , Lian Qiuyu , Xin Hongyi , Zhou Jian , Wang Xiangdong , Powell Charles A. , Hirsch Fred R. , Bai Chunxue , Song Yuanlin , Yin Jun , Yang Dawei
Published: February 2024

Background

Patients who possess various histological subtypes of early‐stage lung adenocarcinoma (LUAD) have considerably diverse prognoses. The simultaneous existence of several histological subtypes reduces the clinical accuracy of the diagnosis and prognosis of early‐stage LUAD due to intratumour intricacy.

Methods

We included 11 postoperative LUAD patients pathologically confirmed to be stage IA. Single‐cell RNA sequencing (scRNA‐seq) was carried out on matched tumour and normal tissue. Three formalin‐fixed and paraffin‐embedded cases were randomly selected for 10× Genomics Visium analysis, one of which was analysed by digital spatial profiler (DSP).

Results

Using DSP and 10× Genomics Visium analysis, signature gene profiles for lepidic and acinar histological subtypes were acquired. The percentage of histological subtypes predicted for the patients from samples of 11 LUAD fresh tissues by scRNA‐seq showed a degree of concordance with the clinicopathologic findings assessed by visual examination. DSP proteomics and 10× Genomics Visium transcriptomics analyses revealed that a negative correlation (Spearman correlation analysis: r = –.886; p = .033) between the expression levels of CD8 and the expression trend of programmed cell death 1(PD‐L1) on tumour endothelial cells. The percentage of CD8+ T cells in the acinar region was lower than in the lepidic region.

Conclusions

These findings illustrate that assessing patient histological subtypes at the single‐cell level is feasible. Additionally, tumour endothelial cells that express PD‐L1 in stage IA LUAD suppress immune‐responsive CD8+ T cells.
Early investigation of a novel SI306 theranostic prodrug for glioblastoma treatment
Authors: Vagaggini Chiara , Petroni Debora , D'Agostino Ilaria , Poggialini Federica , Cavallini Chiara , Cianciusi Annarita , Salis Annalisa , D'Antona Lucia , Francesconi Valeria , Manetti Fabrizio , Damonte Gianluca , Musumeci Francesca , Menichetti Luca , Dreassi Elena , Carbone Anna , Schenone Silvia
Published: February 2024

Glioblastoma multiforme (GBM) is one of the most aggressive malignancies with a high recurrence rate and poor prognosis. Theranostic, combining therapeutic and diagnostic approaches, arises as a successful strategy to improve patient outcomes through personalized medicine.

Src is a non‐receptor tyrosine kinase (nRTK) whose involvement in GBM has been extensively demonstrated. Our previous research highlighted the effectiveness of the pyrazolo[3,4‐d]pyrimidine SI306 and its more soluble prodrug CMP1 as Src inhibitors both in in vitro and in vivo GBM models.

In this scenario, we decided to develop a theranostic prodrug of SI306, ProSI‐DOTA(68Ga) 1, which was designed to target GBM cells after hydrolysis and follow‐up on the disease's progression and improve the therapy's outcome.

First, the corresponding nonradioactive prodrug 2 was tested to evaluate its ADME profile and biological activity. It showed good metabolic stability, no inhibition of CYP3A4, suboptimal aqueous solubility, and slight gastrointestinal and blood‐brain barrier passive permeability. Compound 2 exhibited a drastic reduction of cell vitality after 72 h on two different GBM cell lines (GL261 and U87MG). Then, 2 was subjected to complexation with the radionuclide Gallium‐68 to give ProSI‐DOTA(68Ga) 1. The cellular uptake of 1 was evaluated on GBM cells, highlighting a slight but significant time‐dependent uptake. The data obtained from our preliminary studies reflect the physiochemical properties of 1. The use of an alternative route of administration, such as the intranasal route, could overcome the physiochemical limitations and enhance the pharmacokinetic properties of 1, paving the way for its future development.
Development and optimization of a novel environmental DNA‐based method for moor frog (Rana arvalis) monitoring and comparison with a commercial detection kit
Authors: Olli Suvi , Lampila Petri , Kvist Laura , Honka Johanna
Published: February 2024

Moor frogs (Rana arvalis) are protected by the European Union's Habitats Directive, often making them a target for environmental impact assessments. However, moor frog detection with the traditional method using their mating calls is difficult, time‐consuming, and limited to the short mating season. Environmental DNA (eDNA)‐based methods could be beneficial in moor frog detection since moor frogs are shy and co‐occurring common frogs (R. temporaria) are morphologically similar. Additionally, eDNA‐based methods could even extend the detection period of moor frogs. We tested two different DNA isolation methods and two different eDNA detection methods, Sanger sequencing and quantitative PCR (qPCR), and compared the results to the traditional mating call survey method. In addition, we tested whether linear polyacrylamide treatment would improve eDNA detection. We sampled 27 sites in Finland, of which moor frogs were detected in 17 sites by traditional acoustic survey method, in 20 sites with Sanger sequencing‐based eDNA method, and in 21 sites with qPCR‐based eDNA method. We sampled water bodies during and 3–4 weeks after the end of the mating season. Our results show that both tested eDNA methods (Sanger sequencing and qPCR) can be used to detect moor frogs and extend the moor frog detection period by at least 3–4 weeks, but qPCR slightly outperforms Sanger sequencing. Linear polyacrylamide treatment did not improve the results. Detection probabilities were similar or higher with the eDNA‐based methods than with the traditional survey method, as moor frogs were also detected in water bodies in which mating calls were not heard. Based on our results, eDNA‐based detection methods can be highly beneficial in monitoring the presence of moor frogs and can be used to complement traditional surveys.
Distinguishing heart failure with reduced ejection fraction from heart failure with preserved ejection fraction: A phenomics approach
Authors: van Essen Bart J. , Tharshana Ganash N. , Ouwerkerk Wouter , Yeo Poh Suan Daniel , Sim David , Jaufeerally Fazlur , Ong Hean Yee , Ling Lieng Hsi , Soon Dinna Kar Nee , Lee Shao Guang Sheldon , Leong Gerard , Loh Seet Yoong , San Tan Ru , Ramachandra Chrishan J. , Hausenloy Derek J. , Liew Oi Wai , Chong Jenny , Voors Adriaan A. , Lam Carolyn S.P. , Richards A. Mark , Tromp Jasper
Published: February 2024

Aim

Pathophysiological differences between patients with heart failure with preserved (HFpEF) and reduced (HFrEF) ejection fraction (EF) remain unclear. Therefore we used a phenomics approach, integrating selected proteomics data with patient characteristics and cardiac structural and functional parameters, to get insight into differential pathophysiological mechanisms and identify potential treatment targets.

Methods and results

We report data from a representative subcohort of the prospective Singapore Heart Failure Outcomes and Phenotypes (SHOP), including patients with HFrEF (EF <40%, n = 217), HFpEF (EF ≥50%, n = 213), and age‐ and sex‐matched controls without HF (n = 216). We measured 92 biomarkers using a proximity extension assay and assessed cardiac structure and function in all participants using echocardiography. We used multi‐block projection to latent structure analysis to integrate clinical, echocardiographic, and biomarker variables. Candidate biomarker targets were cross‐referenced with small‐molecule and drug databases. The total cohort had a median age of 65 years (interquartile range 60–71), and 50% were women. Protein profiles strongly discriminated patients with HFrEF (area under the curve [AUC] = 0.89) and HFpEF (AUC = 0.94) from controls. Phenomics analyses identified unique druggable inflammatory markers in HFpEF from the tumour necrosis factor receptor superfamily (TNFRSF), which were positively associated with hypertension, diabetes, and increased posterior and relative wall thickness. In HFrEF, interleukin (IL)‐8 and IL‐6 were possible targets related to lower EF and worsening renal function.

Conclusion

We identified pathophysiological mechanisms related to increased cardiac wall thickness parameters and potentially druggable inflammatory markers from the TNFRSF in HFpEF.
Chemical Structure Elucidation in the Development of Inorganic Drugs: Evidence from Ru‐, Au‐, As‐, and Sb‐based Medicines
Authors: Lance‐Byrne Alissa , Lindquist‐Kleissler Brent , Johnstone Timothy C.
Published: February 2024

Structure elucidation plays a critical role across the landscape of medicinal chemistry, including medicinal inorganic chemistry. Herein, we discuss the importance of structure elucidation in drug development and then provide three vignettes that capture key instances of its relevance in the development of biologically active inorganic compounds. In the first, we describe the exploration of the biological activity of the trinuclear Ru compound called ruthenium red and the realization that this activity derived from a dinuclear impurity. We next explore the development of Au‐based antitubercular and antiarthritic drugs, which features a key step whereby ligands were discovered to bind to Au through S atoms. The third exposition traces the development of As‐based antiparasitic drugs, a key step of which was the realization that the reaction of arsenic acid and aniline does not produce an anilide of arsenic acid, as originally thought, but rather an amino arsonic acid. These case studies provide the motivation for an outlook in which the development of Sb‐based antiparasitic drugs is described. Although antileishmanial pentavalent antimonial drugs remain in widespread use to this day, their chemical structures remain unknown.
Synthesis of glycophospholipid conjugates with mono‐ and disaccharides by enzymatic transphosphatidylation
Authors: Barchan Nikolina , Adlercreutz Patrick
Published: February 2024

Phospholipids, PLs, are interesting and highly abundant amphiphilic molecules, which self‐assemble into 3D nanostructures that have big interest as formulation excipients in, for example, pharma industry. However, the structures that are formed by naturally occurring PLs usually suffer from rigidity problems, and the nanostructures have to be modified in various ways for improved stability. One such approach is by the conjugation of saccharides to the PL head group. In this study, we investigate reaction conditions for the scalable phospholipase D–catalyzed transphosphatidylation reaction for the synthesis of glycophospholipids. Biphasic reaction systems with different solvents are compared with a purely aqueous system with PLs dispersed as vesicles. The investigations showed that use of the biphasic system containing chloroform and a glucose/phosphatidylcholine ratio of 50, in combination with carefully selected enzyme concentration and reaction time, led to an optimized process without any hydrolytic side reaction for the synthesis of phosphatidyl glucose. The reaction system was then applied to a variety of different mono‐ and disaccharides for the synthesis of a range of different glycophospholipids, resulting in yields up to 85% of phosphatidyl monosaccharides and 35% of disaccharides.

Practical Application: Phospholipids and other polar lipids are of great scientific interest as formulation excipients. The chemical structures of lipids used for such applications have major impact on the properties of the self‐aggregated systems. Synthesis of new phospholipids with modified head groups can tremendously widen the portfolio of available choices of formulation excipients and make it possible to make customized formulations with the desired properties. The introduction of saccharides in the hydrophilic part of the phospholipid alters the chemistry of head group and its interaction with surrounding water in vesicle systems and should therefore have a significant effect on its formulating properties compared to natural phospholipids.
Hypervalent Iodine(III)‐Catalysis Using Sulfoxide Oxidant for the Dehydrogenative Cycloisomerization‐Arylation Reaction of 2‐Propargyl 1,3‐Dicarbonyl Compounds
Authors: Umakoshi Yuki , Tsubouchi Akira , Yoshimura Akira , Saito Akio
Published: February 2024

We report herein an unprecedented hypervalent iodine(III)‐catalysis using the activated sulfoxide. Since the present catalytic systems promote the dehydrogenative cycloisomerization‐arylation reaction of 2‐propargyl 1,3‐dicarbonyl compounds with aromatics, this report also provides one of the few methods for iodine(III)‐catalyzed intermolecular carbon‐carbon bond formation of aromatics.
Throwing cold water on muscle growth: A systematic review with meta‐analysis of the effects of postexercise cold water immersion on resistance training‐induced hypertrophy
Authors: Piñero Alec , Burke Ryan , Augustin Francesca , Mohan Adam E. , DeJesus Kareen , Sapuppo Max , Weisenthal Max , Coleman Max , Androulakis‐Korakakis Patroklos , Grgic Jozo , Swinton Paul A. , Schoenfeld Brad J.
Published: February 2024

The purpose of this paper was to systematically review the literature and perform a meta‐analysis of the existing data on the effects of postexercise cold water immersion (CWI) coupled with resistance training (RT) on gains in measures of muscle growth. To locate relevant studies, we comprehensively searched the PubMed/MEDLINE, Scopus, and Web of Science databases. A total of 8 studies met the inclusion criteria; all investigated CWI as the means of cold application. Preliminary analyses conducted on noncontrolled effect sizes provided strong evidence of hypertrophic adaptations with RT that were likely to be at least small in magnitude (SMD0.5 = 0.36 [95% CrI: 0.10–0.61]; p (>0) = 0.995, p (>0.1) = 0.977). In contrast, noncontrolled effect sizes provided some evidence of hypertrophic adaptations with CWI + RT that were likely to be small to negligible in magnitude (SMD0.5 = 0.14 [95% CrI: −0.08–0.36]; p (>0) = 0.906, p (>0.1) = 0.68). The primary analysis conducted on comparative effect sizes provided some evidence of greater relative hypertrophic adaptations with RT compared to CWI + RT (cSMD0.5 = −0.22 [95% CrI: −0.47 to 0.04]) with differences likely to be greater than zero (p (<0) = 0.957) and of at least a small magnitude of effect (p (<−0.1) = 0.834). Meta‐regression did not indicate a potential moderation effect of training status ( = −0.10 [95% CrI: −0.65 to 0.43] p < 0) = 0.653). In conclusion, based on the current data, the application of CWI immediately following bouts of RT may attenuate hypertrophic changes. Given the overall relatively fair to poor quality of the studies examined, the results of the current study should be interpreted with some caution.
Can redistributive policies promote reconciliation beyond its scope? The impact of inequality reduction programs on peacebuilding in Colombia
Authors: Rincón‐Unigarro Camilo , Joel‐Bustos Angie , Pérez‐Farfán Katherine , Velosa‐Campos Astrid , López‐López Wilson
Published: February 2024

Transitional justice jurisdictions aim to promote reconciliation. Although previous research focuses on truth commissions, the reconciliatory role of redistributive justice is less clear. This article investigated the association of conditional cash transfers and victims’ reparation with demand for redistribution, belief in forgiveness, support for the peace process and community participation in Colombia. We analysed three nationally representative samples of the Latin American Public Opinion Project (LAPOP) surveys in 2011 (Study 1; n = 1503), 2016 (Study 2; n = 1563) and 2018 (Study 3; n = 1663). Consistently across studies, conditional cash transfers (and not victim reparation programs) predicted higher community participation, with little effect on other reconciliation indicators. Further, redistribution is indirectly associated with other reconciliation indicators through community participation, supporting the observation that transitional justice relates to reconciliation when it satisfies a need for agency and empowerment. We discuss how the null effects of the victim reparation program suggesting context‐specific constraints.
Optimal Sizing, Gear Ratios, and Shifting Schedule of Battery‐Electric Mining Haul Trucks to Enhance Energy Efficiency
Authors: Liu Qiang , Feng Yanbiao , Liu Bo , Yang Jue , Dong Zuomin
Published: February 2024

At present, mining haul trucks (MHTs) directly deploy the on‐road heavy‐duty trucks’ battery‐electric powertrain, as they can cut down costs and emissions in mining. However, the operating patterns of MHT are different, e.g., ultraduty, low‐speed, and continuous road slopes, resulting in a mismatch between the dynamic and economic performance of mining required and the MHT achieved. The powertrain design and control influence the dynamic and economic performance, which can be quantitatively measured by top speed, gradeability, and energy consumption. This study uses an improved differential evolutionary algorithm to develop an integrated optimization platform to obtain the components sizing, gear ratio, and shifting schedule for the dedicated battery‐electric MHT. Mathematical models are established and validated using on‐site experiment data. An integrated optimization platform is initiated by concurrently formulating the motor sizing, gear ratio, and shifting schedule and solved by the improved differential evolutionary algorithm. Optimization results indicate that the economic performance is enhanced by 10.82%, 11.08%, 11.18%, and 11.20%, respectively, while maintaining or slightly improving the dynamic performance. Besides, the achievable maximum speed at the most common grade is boosted by 11.82%, 6.52%, 7.44%, and 6.52%, respectively. The study provides an approach to developing a battery‐electric powertrain for MHT.
Current progress in quantifying and monitoring instream large wood supply and transfer in rivers
Authors: Ruiz‐Villanueva Virginia , Aarnink Janbert , Ghaffarian Hossein , Gibaja del Hoyo Javier , Finch Bryce , Hortobágyi Borbála , Vuaridel Marceline , Piégay Hervé
Published: February 2024

Large wood drives both the form and function of gravel‐bed rivers draining forested basins. Previously overlooked benefits of wood in rivers are now widely recognized. Together with flow and sediment regimes, the wood regime controls rivers' physical and ecological integrity. Yet large quantities of wood transported during floods can pose additional hazards, potentially damaging infrastructures like bridges or dams and exacerbating flooding. However, unlike the water and sediment regimes intensively studied over the past decades, the instream wood regime or budgeting has been only recently defined and thus is still rarely quantified. The instream wood budget describes the cascading processes from supply or recruitment, entrainment, and transport to deposition, storage and decay (i.e., fragmentation or decomposition). These processes show high spatial and temporal variability but can be characterized by magnitude, frequency, timing, duration and mode. Instream wood budgeting is challenging, primarily because of the lack of observations, monitoring stations, and standardized protocols to acquire data. This contribution reviews the most recent advances to quantify the different instream wood budget components, notably the wood supply, and transfer. Case studies showing applications of biogeochemistry, videography, artificial intelligence, numerical modelling or tracking illustrate the current progress. Because critical challenges remain, we identify and describe some of them and discuss how the wood in riverine sciences may develop in the future.
Improvement of MQTT semantic to minimize data flow in IoT platforms based on distributed brokers
Authors: Kamoun Karim , Hmissi Fatma , Ouni Sofiane , Ouni Sonia
Published: February 2024

Message queuing telemetry transport (MQTT) is an application layer protocol that enables effective device communication in the Internet of Things (IoT). MQTT operates according to a publish‐subscribe model, where a broker receives messages from the publishers and then forwards them to the subscribers. However, existing cloud‐based MQTT brokers lead to network bottlenecks due to the large number of devices that interact with them. Therefore, mist computing is involved, where the MQTT brokers are deployed closer to the IoT devices and the workload is distributed across multiple brokers. Nevertheless, the distributed mist‐based MQTT architecture introduces serious issues caused by the massive volume of flow exchanged by IoT devices. In this article, we introduce MQTT‐SD to address these issues. MQTT‐SD enhances MQTT protocol syntax with fusion semantic aggregation. It accomplishes MQTT topic fusion on the MQTT broker side with consideration of topics' distribution. We carried out extensive simulation and emulation to demonstrate MQTT‐SD efficacy. The results show that MQTT‐SD reduces MQTT flow and has the lowest traffic load compared to MQTT+ and MQTT‐MFA.
Bias‐adjusted and downscaled humidex projections for heat preparedness and adaptation in Canada
Authors: Chow Kenneth Kin Cheung , Sankaré Housseyni , Diaconescu Emilia P. , Murdock Trevor Q. , Cannon Alex J.
Published: February 2024

To help with preparedness efforts of Canadian public health and safety systems for adaptation to climate change, the humidity index (humidex) and three threshold‐based humidex indices (annual number of days with humidex greater than 30, 35 and 40) were computed for a multi‐model ensemble of climate change projections, over Canada. The ensemble consists of one run from each 19 Coupled Model Intercomparison Project Phase 6 (CMIP6) global climate models and offers historical simulations starting in 1950 and future projections out to 2100 following Shared Socioeconomic Pathways (SSPs): SSP1‐2.6, SSP2‐4.5 and SSP5‐8.5. Each ensemble member was bias‐adjusted and statistically downscaled using the Multivariate bias correction—N‐dimensional probability density function transform (MBCn) with hourly data from ERA5‐Land as the target dataset and following a method proposed by Diaconescu et al. (2023; International Journal of Climatology, 43, 837) to calculate humidex from daily climate model outputs. This paper details the steps for data production including evaluation of the target historical gridded data and selection of downscaling method and presents some of the resulting humidex projections at the end of the century.
Revealing genomic heterogeneity and commonality: A penalized integrative analysis approach accounting for the adjacency structure of measurements
Authors: Wang Xindi , Jiang Yu , Sun Yifan
Published: February 2024

Advancements in high‐throughput genomic technologies have revolutionized the field of disease biomarker identification by providing large‐scale genomic data. There is an increasing focus on understanding the relationships among diverse patient groups with distinct disease subtypes and characteristics. Complex diseases exhibit both heterogeneity and shared genomic factors, making it essential to investigate these patterns to accurately detect markers and comprehensively understand the diseases. Integrative analysis has emerged as a promising approach to address this challenge. However, existing studies have been limited by ignoring the adjacency structure of genomic measurements, such as single nucleotide polymorphisms (SNPs) and DNA methylations. In this study, we propose a structured integrative analysis method that incorporates a spline type penalty to accommodate this adjacency structure. We utilize a fused lasso type penalty to identify both heterogeneity and commonality across the groups. Extensive simulations demonstrate its superiority compared to several direct competing methods. The analysis of The Cancer Genome Atlas melanoma data with DNA methylation measurements and GENEVA diabetes data with SNP measurements exhibit that the proposed analysis lead to meaningful findings with better prediction performance and higher selection stability.
Poor olfaction prior to cardiac surgery: Association with cognition, plasma neurofilament light, and post‐operative delirium
Authors: Kamath Vidyulata , Yanek Lisa R. , Neufeld Karin J. , Lewis Alexandria , Aziz Hamza , Le Lan M. , Tian Jing , Moghekar Abhay , Hogue Charles W. , Brown Charles H.
Published: February 2024

Objectives

Post‐operative delirium (POD) affects up to 50% of cardiac surgery patients, with higher incidence in older adults. There is increasing need for screening tools that identify individuals most vulnerable to POD. Here, we examined the relationship between pre‐operative olfaction and both incident POD and POD severity in patients undergoing cardiac surgery. We also examined cross‐sectional relationships between baseline olfaction, cognition, and plasma neurofilament light (NfL).

Methods

Individuals undergoing cardiac surgery (n = 189; mean age = 70 years; 75% men) were enrolled in a clinical trial of cerebral autoregulation monitoring. At baseline, odor identification performance (Brief Smell Identification Test), cognitive performance, and plasma concentrations of NfL levels (Simoa™ NF‐Light Assay) were measured. Delirium was assessed with the Confusion Assessment Method (CAM) or CAM‐ICU, and delirium severity was assessed using the Delirium Rating Scale‐Revised‐98. The association of baseline olfaction, delirium incidence, and delirium severity was examined in regression models adjusting for age, duration of cardiopulmonary bypass, logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE), and baseline cognition.

Results

Olfactory dysfunction was present in 30% of patients, and POD incidence was 44%. Pre‐operative olfactory dysfunction was associated with both incident POD (OR = 3.17, p = 0.001) and greater severity of POD after cardiac surgery (OR = 3.94 p < 0.001) in models adjusted for age, duration of bypass, and a surgical risk score. The addition of baseline cognition attenuated the strength of the association, but it remained significant for incident POD (OR = 2.25, p = 0.04) and POD severity (OR 2.10, p = 0.04). Poor baseline olfaction was associated with greater baseline cognitive dysfunction (p < 0.001) and increased baseline plasma NfL concentrations (p = 0.04). Neither age, cognition, nor baseline NFL concentration modified the association of impaired olfaction and delirium outcomes.

Conclusions

Olfactory assessment may be a useful pre‐surgical screening tool for the identification of patients undergoing cardiac surgery at increased risk of POD. Identifying those at highest risk for severe delirium and poor cognitive outcomes following surgery would allow for earlier intervention and pre‐operative rehabilitation strategies, which could ultimately impact the functional disability and morbidity associated with POD.
Loco‐regional radiotherapy in de novo metastatic nasopharyngeal carcinoma with chemotherapy and immunotherapy: A real‐world retrospective study from two cancer centers
Authors: Ma Li , Lan Fengming , Chen Peng , Lei Ling , Zou Teng , Fu Fangmeng , Wu Runye , Jin Jing , Zhang Jianghu
Published: February 2024

Background

Immunochemotherapy has become the first‐line treatment for initial diagnosed metastatic nasopharyngeal carcinoma (mNPC). Loco‐regional radiotherapy combined with systemic chemotherapy significantly improves the survival. However, the safety and efficacy of loco‐regional radiotherapy combined with immunochemotherapy remained unknown.

Methods

Patients with de novo mNPC who received immunochemotherapy followed by loco‐regional radiotherapy were included from two cancer centers. Toxicity and treatment response were assessed using CTCAE 5.0 and RECIST 1.1, respectively. Overall survival (OS) and progression‐free survival (PFS) were analyzed using the Kaplan–Meier method.

Results

From 2019 to 2021, a total of 16 patients were retrospectively analyzed. The median follow‐up was 28 months (range 14–47 months). No one died. One‐year, 2‐year, and 3‐year PFS rate was 93.8%, 58.4% and 50.1%, respectively. Radiotherapy‐related acute severe (grade 3 or higher) toxicity was dermatitis (1/16, 6.3%) and mucositis (2/16, 12.5%).

Conclusions

Loco‐regional radiotherapy provided a promising efficacy with modest toxicity for patients with mNPC who received immunochemotherapy.
Investigating the association between socioeconomic status and language skills in children with autism spectrum disorder or other developmental delays
Authors: Pecukonis Meredith , Levinson Julia , Chu Andrea , Broder‐Fingert Sarabeth , Feinberg Emily , Cabral Howard , Tager‐Flusberg Helen
Published: February 2024

Numerous studies have reported that socioeconomic status (SES) predicts language skills in typically developing children. However, this association has been less systematically studied in children with developmental disabilities, such as autism spectrum disorder (ASD) or other developmental delays (DD). In the present study, we examined the association between SES, operationalized as maternal education attainment and health insurance status, and receptive and expressive language skills in a sample of children from lower SES, racial/ethnic minority families at increased ‘clinical risk’ for ASD based on early screening. Neither maternal education attainment nor health insurance status were significantly associated with children's language skills. Expressive and receptive language skills were significantly higher in children with DD compared to children with ASD. Findings differ from previously published work, highlighting the importance of study replication. Further research is needed to understand why the association between SES and children's language skills might vary across samples.

Highlights

Examined association between socioeconomic status (SES) and language skills in children at ‘clinical risk’ for autism based on early screening.

Found no associations between measures of SES and children's language skills.

Results differ from previously published work, highlighting the importance of replicating studies with lower SES, racial/ethnic minority families.
How to improve initial diagnostic accuracy of kidney tumours in childhood?—A non‐invasive approach
Authors: Welter Nils , Metternich Gregor , Furtwängler Rhoikos , Bayoumi Ahmed , Mergen Marvin , Kager Leo , Vokuhl Christian , Warmann Steven W. , Fuchs Jörg , Meier Clemens‐Magnus , Melchior Patrick , Gessler Manfred , Wagenpfeil Stefan , Schenk Jens‐Peter , Graf Norbert
Published: February 2024

Non‐invasive differentiation of paediatric kidney tumours is particularly important in the SIOP‐RTSG protocols, which recommend pre‐operative chemotherapy without histological confirmation. The identification of clinical and tumour‐related parameters may enhance diagnostic accuracy. Age, metastases, and tumour volume (TV) were retrospectively analysed in 3306 patients enrolled in SIOP/GPOH 9, 93‐01, and 2001 including Wilms tumour (WT), congenital mesoblastic nephroma (CMN), clear cell sarcoma (CCSK), malignant rhabdoid tumour of the kidney (MRTK), and renal cell carcinoma (RCC). WT was diagnosed in 2927 (88.5%) patients followed by CMN 138 (4.2%), CCSK 126 (3.8%), MRTK 58 (1.8%) and RCC 57 (1.7%). CMN, the most common localized tumour (71.6%) in patients younger than 3 months of age, was diagnosed earliest and RCC the latest (median age [months]: 0 and 154, respectively) both associated with significantly smaller TV (median TV [mL]: 67.2 and 45.0, respectively). RCC occurred in >14% of patients older than 120 months or older than 84 months with TV <100 mL. Receiver operating characteristic analyses discriminated WT from CMN, RCC and MRTK regarding age (AUC = 0.976, 0.929 and 0.791) and TV (AUC = 0.768, 0.813 and 0.622). MRTK had the highest risk of metastasis (37.9%) despite young age, whereas the risk of metastasis increased significantly with age in WT. Age and TV at diagnosis can differentiate WT from CMN and RCC. MRTK must be considered for metastatic tumours at young age. Identification of CCSK without histology remains challenging. Combined with MRI‐characteristics, including diffusion‐weighted imaging, and radiomics and liquid biopsies in the future, our approach allows optimization of biopsy recommendations and prevention of misdiagnosis‐based neoadjuvant treatment.
Assessing zero‐till direct seeding at variable water stress levels compared to traditional puddled transplanting of rice under groundwater‐fed irrigation systems in north‐west India
Authors: Kumar Satyendra , Narjary Bhaskar , Paudyal Kalpana , Yadav Rajender Kumar , Kamra Sushil Kumar
Published: February 2024

Irrigation of rice using groundwater is considered one of the main contributors to north‐west India's declining water level. The present study hypothesizes that zero‐till direct seeding of rice (ZTDSR) with the optimum irrigation schedule may reduce irrigation compared to puddled transplanted rice (PTR). Crop growth stage‐dependent predefined soil matric potential (SMP), that is, −15, −30 and −45 kPa based irrigation schedules either during the entire growing period or their combinations during the vegetative phase in ZTDSR, were compared with PTR for two consecutive seasons. The results showed that irrigation in ZTDSR at lower SMP at any growth stage caused adverse effects on yield. Irrigation at −15 kPa during the entire crop season with straw mulch was found to be the best schedule for ZTDSR. ZTDSR with −15 kPa irrigation, however, saved 36.2 cm of water and recorded higher water productivity but produced 20% less grain yield over the prevailing PTR. A higher groundwater system loss (GWSL) was found in the PTR (29.2 cm) than in the best ZTDSR (23.6 cm) schedule, which indicates better groundwater management in the ZTDSR than in the PTR. Hence, the ZTDSR has the potential to save irrigation, achieve higher water productivity and manage the depletion of groundwater resources in rice–wheat dominant north‐west India.
Potential Complications in the Use of Wheat Bran for Constipation in Infancy
Authors: Zoppi G. , Gobio‐Casali L. , Deganello A. , Astolfi R. , Saccomani F. , Cecchettin M.
Published: February 2024

A commercially available wheat bran preparation has been given to six infants between the ages of 6 and 16 months suffering from constipation not due to metabolic or anatomic causes. In all infants, normal bowel movements reappeared after a month of a diet containing bran. After a month on this diet, we observed the following: a decrease in blood levels of calcium, phosphate, and trace elements; an increase in fecal excretion of biliary salts and cholesterol; and an appearance of predominantly proteolytic fecal flora over the saccharolitic flora. These findings, especially the first one, indicate that bran preparations should be used in infancy with extreme caution because of possible side effects on the patient's nutritional status and growth. If bran is used, blood levels of minerals should be repeatedly checked in order to prevent the appearance of vitamin D‐dependent rickets and the depletion of trace elements.
Postnatal Development of Peptidase Enzymes in Rat Small Intestine
Authors: Vaeth Gregory F. , Henning Susan J.
Published: February 2024

The development and distribution of peptidase activity in mucosal homogenates of rat small intestine has been investigated. Substrates used were glycyl‐L‐leucine (GL), L‐seryl‐L‐methionine (SM), and L‐leucyl‐glycyl‐glycine (LGG). During the first 2 weeks of life there was high peptidase activity toward GL and SM in the distal regions of the small intestine. In the third postnatal week, activity in the distal small intestine toward GL and SM decreased, while activity in the proximal small intestine increased. In contrast, there was no difference in activity toward LGG along the length of the small intestine, nor was there a developmental change. Activity toward all three substrates was not affected by cortisone acetate treatment. However, the classical effect of glucocorticoids on sucrase activity and body weight was observed. All peptidases studied showed maximal activities at neutral pH, indicating that they were not lysosomal in origin. Activity towards GL and SM was predominantly located in the cytosol. It is suggested that these dipeptidase activities play a role in the terminal steps of protein digestion following pinocytosis and lysosomal hydrolysis.
In Vivo Intestinal Zinc Transport in Rats
Authors: Meneely Raymond , Ghishan Fayez K.
Published: February 2024

We compared the in vivo transport of zinc in segments of jejunum, ileum, and colon of 2‐week‐old (suckling) and 6‐week‐old (adolescent) rats. In normal rats, net absorption and lumen to mucosa flux of zinc, normalized for differences in size of the intestine (μmol/h/g dry weight) were significantly greater in all perfused segments of the suckling compared with corresponding segments of the adolescent rats (p < 0.05). Moreover, zinc transport rates in colonic segments of the suckling rats were significantly greater than corresponding transport rates in the small intestinal segments (p < 0.05). In the adolescent rats, transport rates in the colonic segments were similar to corresponding rates in the small intestinal segments. Growth retardation (pups raised with mothers fed a diet deficient in protein) appeared to have no effect on net absorption or lumen to mucosa flux of zinc in suckling rats, but significantly enhanced net absorption and lumen to mucosa flux of zinc in the adolescent rats.