bluuebunny/crossref_metadata_2025 huggingface dataset:
Deuterium metabolic imaging for 3D mapping of glucose metabolism in humans with central nervous system lesions at 3T
Authors: Adamson Philip M. , Datta Keshav , Watkins Ron , Recht Lawrence D. , Hurd Ralph E. , Spielman Daniel M.
Published: October 2023

Purpose

To explore the potential of 3T deuterium metabolic imaging (DMI) using a birdcage 2H radiofrequency (RF) coil in both healthy volunteers and patients with central nervous system (CNS) lesions.

Methods

A modified gradient filter, home‐built 2H volume RF coil, and spherical k‐space sampling were employed in a three‐dimensional chemical shift imaging acquisition to obtain high‐quality whole‐brain metabolic images of 2H‐labeled water and glucose metabolic products. These images were acquired in a healthy volunteer and three subjects with CNS lesions of varying pathologies. Hardware and pulse sequence experiments were also conducted to improve the signal‐to‐noise ratio of DMI at 3T.

Results

The ability to quantify local glucose metabolism in correspondence to anatomical landmarks across patients with varying CNS lesions is demonstrated, and increased lactate is observed in one patient with the most active disease.

Conclusion

DMI offers the potential to examine metabolic activity in human subjects with CNS lesions with DMI at 3T, promising for the potential of the future clinical translation of this metabolic imaging technique.
Association of baseline physical activity participation with participant characteristics and outcomes following education and exercise‐therapy in people with knee osteoarthritis: A GLA:D® Australia prospective cohort study
Authors: Bell Emily C. , Pazzinatto Marcella F. , Wallis Jason A. , Kemp Joanne L. , Skou Søren T. , O’Halloran Paul , Crossley Kay M. , De Oliveira Silva Danilo , Semciw Adam I. , Dundules Karen , Barton Christian J.
Published: October 2023

Objectives

To investigate whether participants with knee osteoarthritis classified as ‘more’ or ‘less’ physically active at baseline differ in characteristics and/or outcomes at baseline and at 3 and 12 months following the commencement of an education and exercise‐therapy program.

Methods

Prospective cohort study using the GLA:D® Australia registry. The University of California, Los Angeles Physical Activity Scale (UCLA) participant data dichotomised as ‘more’ (≥7) or ‘less’ active (≤6). Groups were compared using chi‐square (obesity [baseline only], comorbidity prevalence, medication consumption, fear of damage from physical activity); and linear mixed model regression (12‐item Injury Osteoarthritis Outcome Score [KOOS‐12], pain [visual analogue scale], health‐related quality of life [QoL] [EQ‐5D‐5L]) statistics, adjusted for age, sex and baseline physical activity at 3 and 12 months.

Results

We included 1059 participants (70% female). At baseline, 267 (25%) were classified as ‘more’ active, increasing to 29% and 30% at 3 and 12 months, respectively. At baseline, compared to the ‘less’ active group, the ‘more’ active group had a lower proportion of participants who were obese (‘more’ = 21% vs. ‘less’ = 44%), had comorbidities (58% vs. 74%) and consumed medications (71% vs. 85%); lower pain intensity (37 vs. 47); and higher KOOS‐12 (59 vs. 50), and health‐related QoL (0.738 vs. 0.665) scores. When accounting for age, sex and baseline physical activity, improvements seen in knee‐related burden and health‐related QoL were not different between groups at 3 or 12 months. Compared to the ‘less’ active group, the proportion of participants not consuming medication remained higher in the ‘more’ active group at 3 (‘more’ 45% vs. ‘less’ 28%) and 12 months (43% vs. 32%).

Conclusion

‘More’ active people with knee osteoarthritis were less likely to be obese, had fewer comorbidities, lower medication consumption, knee‐related burden and pain intensity, and higher health‐related QoL than ‘less’ active participants at all timepoints.
Visceral adipose tissue reference data computed for GE HealthCare DXA from the National Health and Nutrition Examination Survey data set
Authors: Bennett Jonathan P. , Quon Brandon K. , Fan Bo , Liu En , Kazemi Leila , Villegas‐Valle Rosa C. , Ahgun Raj , Wu Xian‐pin , Zhou Hou‐De , Lu Ying , Shepherd John A.
Published: October 2023

Objective

The National Health and Nutrition Examination Survey (NHANES) characterizes body composition representative of the US population using dual‐energy x‐ray absorptiometry (DXA) scans. These population‐level trends of abdominal subcutaneous and visceral adipose tissue (SAT and VAT) are useful for identifying measures associated with increased disease risk. Recently, VAT and SAT data collected by Hologic DXA in NHANES were published online; however, there are known differences in the absolute calibration of DXA systems by make. The purpose of this study was to create reference tables suitable for calculating z scores and percentile values for GE HealthCare (GEHC) DXA systems.

Methods

DXA scans were acquired on participants aged 8 to 59 years using Hologic systems. DXA measures were converted to GEHC and described using the least median squares curve fitting method in pediatrics (aged <20 years) and adults (aged 20–59 years).

Results

A total of 11,972 adults and 7298 pediatrics were included for this analysis. Adult and pediatric curves were generated by sex and by ethnicity (non‐Hispanic White, non‐Hispanic Black, Hispanic, Asian, Other) and were derived as a function of age.

Conclusions

These results show the ability to generate VAT and SAT reference data for GEHC systems using Hologic DXA data representative of the US youth and adult population.
On the predictive capabilities of non‐local models for ductile crack propagation under different levels of stress triaxiality
Authors: El Khatib Omar , Pham Rinh‐Dinh , Hütter Geralf , Seupel Andreas , Kiefer Bjoern
Published: October 2023

Ductile materials are used in many applications such as hydrogen storage and transport, energy plants and additively manufactured components. High safety standards are vital for such applications, which underline the necessity of thoroughly investigating ductile failure to ensure safety and increase components efficiency. Ductile failure is mainly prompted by the evolution of the so‐called ductile damage, characterized by the nucleation, growth and coalescence of microvoids due to plastic deformation. Moreover, the plastic zones formed at the crack tip of ductile materials exhibit high sensitivity to the stress triaxiality level, which in turn distinctly depends on the geometry of the considered component. The quantification of the stress triaxiality at the crack tip is therefore essential to better understand and predict ductile crack propagation and failure. For that reason, a non‐local ductile damage model is employed in this work to simulate the ductile crack propagation under different stress triaxiality conditions. Different geometries are considered, such as constrained geometries of notched bending specimens and unconstrained geometries of center cracked tension specimens, which characterize the different triaxiality levels. To address the effects of thickness and initial crack length, three‐dimensional geometries are simulated, which account for the out‐of‐plane crack‐tip constraints. Finally, to evaluate the prediction quality of the simulations, corresponding experiments have been carried out and direct comparisons are conducted, with respect to the crack length, ductile crack propagation and resistance curves.
Initial interactions with the FDA on developing a validation dataset as a medical device development tool
Authors: Hart Steven , Garcia Victor , Dudgeon Sarah N , Hanna Matthew G , Li Xiaoxian , Blenman Kim RM , Elfer Katherine , Ly Amy , Salgado Roberto , Saltz Joel , Gupta Rajarsi , Hytopoulos Evangelos , Larsimont Denis , Lennerz Jochen , Gallas Brandon D
Published: October 2023

Quantifying tumor‐infiltrating lymphocytes (TILs) in breast cancer tumors is a challenging task for pathologists. With the advent of whole slide imaging that digitizes glass slides, it is possible to apply computational models to quantify TILs for pathologists. Development of computational models requires significant time, expertise, consensus, and investment. To reduce this burden, we are preparing a dataset for developers to validate their models and a proposal to the Medical Device Development Tool (MDDT) program in the Center for Devices and Radiological Health of the U.S. Food and Drug Administration (FDA). If the FDA qualifies the dataset for its submitted context of use, model developers can use it in a regulatory submission within the qualified context of use without additional documentation. Our dataset aims at reducing the regulatory burden placed on developers of models that estimate the density of TILs and will allow head‐to‐head comparison of multiple computational models on the same data. In this paper, we discuss the MDDT preparation and submission process, including the feedback we received from our initial interactions with the FDA and propose how a qualified MDDT validation dataset could be a mechanism for open, fair, and consistent measures of computational model performance. Our experiences will help the community understand what the FDA considers relevant and appropriate (from the perspective of the submitter), at the early stages of the MDDT submission process, for validating stromal TIL density estimation models and other potential computational models. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
Delivery of re‐irradiation and complex palliative radiotherapy using proton therapy in pediatric cancer patients
Authors: Berlin Eva , Eisenberg Rachel , Hill‐Kayser Christine , Lustig Robert A. , Kurtz Goldie , Cummings Elizabeth , LaRiviere Michael
Published: October 2023

Background

The intent of this study is to characterize indications for pediatric palliative‐intent proton radiation therapy (PIPRT).

Procedure

We retrospectively reviewed patients 21 years and younger who received PIPRT. We defined PIPRT as radiotherapy (RT) aimed to improve cancer‐related symptoms/provide durable local control in the non‐curative setting. Mixed proton/photon plans were included. Adjacent re‐irradiation (reRT) was defined as a reRT volume within the incidental dose cloud of a prior RT target, whereas direct reRT was defined as in‐field overlap with prior RT target. Acute toxicity during RT until first inspection visit was graded according to the Common Terminology Criteria for Adverse Events. The Kaplan–Meier method, measured from last PIPRT fraction, was used to assess progression‐free survival (PFS) and overall survival (OS).

Results

Eighteen patients underwent PIPRT between 2014 and 2020. Median age at treatment start was 10 years [2–21]. Median follow‐up was 8.2 months [0–48]. Treatment sites included: brain/spine [10], abdomen/pelvis [3], thorax [3], and head/neck [2]. Indications for palliation included: durable tumor control [18], neurologic symptoms [4], pain [3], airway compromise [2], and great vessel compression [1]. Indications for protons included: reRT [15] (three adjacent, 12 direct), craniospinal irradiation [4], reduction of dose to normal tissues [3]. Sixteen experienced grade (G) 1–2 toxicity; two G3. There were no reports of radionecrosis. Median PFS was 5.3 months [95% confidence interval (CI): 2.7–16.3]. Median OS was 8.3 months [95% CI: 5.5–26.3].

Conclusions

The most common indication for PIPRT was reRT to provide durable tumor control. PIPRT appears to be safe, with no cases of high‐grade toxicity.
The evaluation of antimicrobial stewardship for bacterial meningitis in neonates
Authors: Chen Xinsi , Feng Kun , Zhang Yu , Wang Yongming , Zhao Qianqian , Hu Ya , Liu Kaizhen , Wei Hong , Hua Ziyu
Published: October 2023

Bacterial meningitis (BM) is potentially life threatening in neonates, but the duration of antibiotic therapy is not well established. We aimed to compare the efficacy and safety among neonates suffering from BM of a relatively shortened duration of antibiotic treatment to the currently recommended course. We did a retrospective cohort study in neonates (gestational age [GA] or corrected GA ≥35 weeks) diagnosed with BM. Neonates in the study group were assigned to withdraw the antibiotics on condition that they were clinically stable after taking sufficient antibiotics with normal serological inflammatory biomarkers, whereas the cerebrospinal fluid (CSF) indicators remain abnormal. Neonates in the control group were treated until both serological and CSF indicators returned to normal as recommended. The incidence of recurrent infection after the discontinuation of antibiotics and adverse drug reactions (ADRs) during hospitalization was measured. A total of 233 neonates were enrolled, of whom 160 were assigned to a shortened antibiotic duration and 73 were treated according to the current guidelines. Twelve patients (7.5%) relapsed in the study group, whereas 4 (5.5%) relapsed in the control group (χ2 = 0.320, p = 0.572). The incidences of ADRs were similar in both groups (p > 0.05). The study indicates that antibiotics might be safely discontinued in neonates (GA ≥35 weeks) diagnosed with BM who are clinically stable or improving after antibiotic treatment and feature normal serological inflammatory markers, no severe complications, and no evidence of systemic infection, even if CSF parameters are not completely normal.
Optimal design and operation of reactive extrusion processes: Modeling, model validation, and optimization algorithm
Authors: Cegla Maximilian , Engell Sebastian
Published: October 2023

In this work, a methodology for the optimal design and operation of reactive extrusion processes in twin‐screw extruders is presented. As a process model, a very accurate mechanistic finite volume twin‐screw extruder model is used which is adapted to the reactive extrusion case. In the model, in contrast to other models, the pressure is described as a differential state in order to have a consistent set of equations. The model is compared to other models and advantages and disadvantages with respect to accuracy and computation time are discussed. For optimization, a memetic optimization algorithm (MA) that consists of a combination of a local optimization for the continuous operating parameters and an evolutionary algorithm (EA) for the global optimization of the discrete decision variables is employed to overcome the drawback of the longer model simulation time compared to simpler models. A reduction of optimization time by 90% for the MA compared to the EA was observed. The presented modeling and optimization methodology is validated on the widely investigated reactive extrusion process for ε‐Caprolactone. The methodology is very flexible and the underlying model has good prediction characteristics, thus it is applicable to a wide range of reactive extrusion processes of industrial interest.

Highlights

Simulation and optimization of reactive extrusion.

Improved mechanistic twin‐screw extruder model.

Novel approaches for pressure and residence time modeling.

Efficient combination of local and global optimization in a memetic algorithm.

Benchmarking of the optimization results and performance with literature data.
Effect of magnesium hydroxide and graphene nanoplatelets on the properties of peroxide cross‐linked linear low‐density polyethylene nanocomposite
Authors: Yussuf Abdirahman A. , Al‐Saleh Mohammad A. , Samuel Jacob , Ahmad Nasser , AlShammar Tahani , Al‐Banna Aseel , Abraham Gils
Published: October 2023

Linear low‐density polyethylene (LLDPE) and different concentrations (5‐20 wt%) of magnesium hydroxide (MAH) as a filler either with or without the addition of graphene nanoplatelets (GNPs) were peroxide cross‐linked using dicumyl peroxide as a cross‐linking agent in a twin‐screw extruder. The mechanical, thermal stability, flame retardancy, morphological, and rheological properties of the prepared samples were investigated. The mechanical properties of the peroxide cross‐linked LLDPE samples with higher MAH and GNP in the matrix were significantly improvement compared to neat LLDPE. This indicates that the addition of MAH and GNP to the peroxide cross‐linked LLDPE matrix could be suitable reinforcing fillers to achieve better and enhanced mechanical properties, particularly tensile strength. Conversely, a significant decrease in the elongation at break values was found for peroxide cross‐linked LLDPE samples compared to neat LLDPE. Similarly, results of thermogravimetric analysis revealed remarkable thermal stability enhancement in the peroxide cross‐linked LLDPE samples with higher MAH and GNP compared to neat LLDPE. The results from UL94 test demonstrated that the peroxide cross‐linked LLDPE samples comprising higher MAH with GNP exhibited improved V = 0 rating compared to poor no rating (NR) for neat LLDPE. Furthermore, the scanning electron microscope and digital images shown improved flame retardancy properties for these samples because of the formation of protective char layer on the sample surface. The complex viscosity for the peroxide cross‐linked LLDPE samples, at lower frequency, increased with increasing MAH loading and further addition of GNP compared to neat LLDPE.

Highlights

Cross‐linked polyethylene with flame retardant (FR) and nanofiller were prepared.

Effects of cross‐linking and FR on the final properties of the polymer were studied.

20wt% FR with 3 phr nanofiller promoted the final properties of the polymer.

Higher filler loading in the polymer improved flame retardancy and thermal stability.

Combined effect of cross‐linking and FR has shown major improvement.
Consensus statement: An evidence‐based review of exercise, rehabilitation, rest, and return to activity protocols for the treatment of concussion and mild traumatic brain injury
Authors: De Luigi Arthur J. , Bell Kathleen R. , Bramhall Joe P. , Choe Meeryo , Dec Katherine , Finnoff Jonathan T. , Halstead Mark , Herring Stanley A. , Matuszak Jason , Raksin P. B. , Swanson Jennifer , Millett Carolyn
Published: October 2023

Background

Early diagnosis and appropriate management of concussion/mild traumatic brain injury (mTBI) is critical for preventing poor outcomes and minimizing health care burden. Current clinical guidelines for concussion management focus mostly on diagnosis and return to cognitive and physical activity but provide limited guidance on the use of specific therapeutic interventions.

Objective

To systematically review the available evidence on therapeutic interventions for concussion/mTBI and develop an evidence‐based consensus statement on the use of these interventions in clinical practice.

Literature Survey

A systematic literature search was performed first in 2018 and 2019, and again in 2022, to identify relevant original research on these interventions. A total of 6303 articles were retrieved through the systematic literature search and screened for inclusion. Eighty articles met inclusion criteria and were included in this review and consensus process.

Methodology

A multispecialty panel was convened to explore management of concussion/mTBI. Interventions evaluated included rest, exercise, rehabilitation, and return to activity (RTA) protocols. Studies were assessed for relevance and methodologic quality and were voted upon to develop an evidence‐based consensus statement on the therapeutic appropriateness of these interventions for concussion/mTBI. A meta‐analysis was not performed.

Synthesis

There was sufficient evidence to recommend exercise as an appropriate therapy for adolescents with acute concussion/mTBI. In other age groups and for other therapeutic modalities, although some studies demonstrated benefits for some of the interventions, mixed results and study limitations prevented the panel from drawing firm conclusions on the efficacy of those interventions. The panel found evidence of detrimental effects from strict rest and high‐intensity physical activity.

Conclusions

The panel recommended exercise as an appropriate therapy for acute concussion in adolescents. The evidence on other therapeutic interventions for concussion/mTBI remains limited to small randomized controlled trials and observational studies of moderate to low quality. The panel found no strong evidence to support or recommend against the other evaluated interventions but found most interventions to be safe when used judiciously and in consideration of individual patient needs. High‐quality randomized studies with sufficient power are needed to evaluate the effects of rest, rehabilitation, and RTA protocols for the management of concussion/mTBI.
Exercise‐induced hypoalgesia with end‐stage knee osteoarthritis during different blood flow restriction levels: Sham‐controlled crossover study
Authors: Ogrezeanu Daniel C. , López‐Bueno Laura , Sanchís‐Sánchez Enrique , Suso‐Martí Luis , López‐Bueno Rubén , Núñez‐Cortés Rodrigo , Cruz‐Montecinos Carlos , Pérez‐Alenda Sofía , Casaña José , Gargallo Pedro , Calatayud Joaquín
Published: October 2023

Background

Blood flow restriction (BFR) training could be a valuable treatment to induce exercise‐induced hypoalgesia (EIH) in patients with end‐stage knee osteoarthritis. However, the use of BFR in these patients is poorly explored and there is no evidence about the training dosage needed.

Objective

To evaluate the effect of resistance training protocols with different occlusion levels of blood flow restriction (BFR) on EIH in patients with end‐stage knee osteoarthritis.

Design

Crossover study.

Setting

University physical exercise laboratory.

Participants

26 adults with end‐stage knee osteoarthritis.

Interventions

Patients performed four sets (30, 15, 15, and 15 repetitions) separated by 1‐minute rests of three protocols/sessions of low‐load (30% one‐repetition‐maximum) seated knee extensions with elastic bands and BFR: placebo (sham BFR), BFR at 40% arterial occlusion pressure (AOP) and BFR at 80% AOP.

Main Outcome Measures

Pressure Pain Thresholds (PPT) and Visual Analog Scale (VAS) collected before, immediately after session, and after 10 minutes.

Results

No differences in EIH were found between the different levels of BFR. However, 80% AOP protocol worsened VAS scores immediately (mean difference [MD]: −21.2 (95% confidence interval [CI] −33.9 to −8.5) while improving PPT immediately (MD affected limb: −.6 [95% CI −1.1 to −.2]); contralateral: −.6 (95% CI −1.0 to −.2]) and at 10 minutes (MD affected limb: −.6 [95% CI) −1.2 to −.1]; contralateral: −.7 [95% CI −1.1 to −.2]; and forearm: −.5 [95% CI −.9 to −.05]) post‐exercise compared to baseline.

Conclusions

There is no EIH difference after using different occlusion levels. EIH is modulated by pain‐related psychological constructs and self‐perceived health status.
QTY code designed antibodies for aggregation prevention: A structural bioinformatic and computational study
Authors: Li Mengke , Wang Yanze , Tao Fei , Xu Ping , Zhang Shuguang
Published: October 2023

Therapeutic monoclonal antibodies are the most rapidly growing class of molecular medicine, and they are beneficial to the treatment of a broad spectrum of human diseases. However, the aggregation of antibodies during the process of manufacture, distribution, and storage poses significant challenges, potentially compromising efficacy and inducing adverse immune responses. We previously conceived a QTY (glutamine, threonine, tyrosine) code, a simple tool for enhancing protein water‐solubility by systematically pairwise replacing hydrophobic residues L (leucine), V (valine)/I (isoleucine), and F (phenylalanine). The QTY code offers a promising alternative to traditional methods of controlling aggregation in integral transmembrane proteins. In this study, we designed variants of four antibodies applying the QTY code, changing only the β‐sheets. Through the structure‐based aggregation analysis, we found that these QTY antibody variants demonstrated significantly decreased aggregation propensity compared to their wild‐type counter parts. Our results of molecular dynamics simulations showed that the design by QTY code is capable of maintaining the antigen‐binding affinity and structural stability. Our structural informatic and computational study suggests that the QTY code offers a significant potential in mitigating antibody aggregation.
Design and synthesis of fosmidomycin analogs containing aza‐linkers and their biological activity evaluation
Authors: Wu Xin , Bu Mengwei , Yang Zili , Ping Hongrui , Song Chunlin , Duan Jiang , Zhang Aidong
Published: October 2023

BACKGROUND

The enzymes involved in the 2‐C‐methyl‐d‐erythritol 4‐phosphate (MEP) pathway are attractive targets of a new mode of action for developing anti‐infective drugs and herbicides, and inhibitors against 1‐deoxy‐d‐xylulose 5‐phosphate reductoisomerase (IspC), the second key enzyme in the pathway, have been intensively investigated; however, few works are reported regarding IspC inhibitors designed for new herbicide discovery.

RESULTS

A series of fosmidomycin (FOS) analogs were designed with nitrogen‐containing linkers replacing the trimethylene linker between the two active substructures of FOS, phosphonic acid and hydroxamic acid. Synthesis followed a facile three‐step route of sequential aza‐Michael addition of α‐amino acids to dibenzyl vinylphosphonate, amidation of the amino acid carboxyl with O‐benzyl hydroxylamine, and simultaneous removal of the benzyl protective groups. Biological activity evaluation of IspC and model plants revealed that some compounds had moderate enzyme and model plant growth inhibition effects. In particular, compound 10g, which has a N‐(4‐fluorophenylethyl) nitrogen‐containing linker, exhibited the best plant inhibition activities, superior to the control FOS against the model plants Arabidopsis thaliana, Brassica napus L., Amaranthus retroflexus and Echinochloa crus‐galli. A dimethylallyl pyrophosphate rescue assay on A. thaliana confirmed that both 10g and FOS exert their herbicidal activity by blocking the MEP pathway. This result consistent with molecular docking, which confirmed 10g and FOS binding to the IspC active site in a similar way.

CONCLUSION

Compound 10g has excellent herbicidal activity and represents the first herbicide lead structure of a new mode of action that targets IspC enzyme in the MEP pathway. © 2023 Society of Chemical Industry.
In vitro inhalation bioaccessibility and health risk assessment of difenoconazole in the atmosphere
Authors: Fang Ke , Xiang Yu‐Xin , Wang Han , Li Ming‐Kun , Jiang Si‐Yuan , Liu Chen‐Jun , Yang Xin , Wei Su‐Wan , Xiao Jin‐Jing , Shi Yan‐Hong , Cao Hai‐Qun
Published: October 2023

BACKGROUND

Assessment of the risk of pesticide inhalation in populations around farmland is necessary because inhalation is one of the ways in which pesticides can risk human health. This study aimed to identify the inhalation risk of difenoconazole on humans by using dose–response and exposure assessments.

RESULTS

In the field simulation application, respiratory exposure in populations around farmland ranged from 71 to 430 ng/m3. Using response surface methodology, the maximum bioaccessibility of difenoconazole in three simulated lung fluids was 35.33% in Gamble's solution (GS), 34.12% in artificial lysosomal fluid (ALF), and 42.06% in simulated interstitial lung fluid (SLF). Taking the proliferation activity of the A549 cell model as the endpoint, the benchmark dose limit and benchmark dose of difenoconazole on A549 cells were 16.36 and 5.60 mg/kg, respectively. The margin of exposure to difenoconazole in GS, ALF and SLF were, respectively, 8.66 × 105 to 5.28 × 106, 8.97 × 105 to 5.47 × 106 and 7.28 × 105 to 4.44 × 106.

CONCLUSION

The risk assessment results indicate that under all circumstances, applying difenoconazole is safe for populations around farmland. However, a fan‐shaped nozzle, suspension concentrate and greater inhalation height increase the risk of inhalation. © 2023 Society of Chemical Industry.
Phytotoxic fungal secondary metabolites as herbicides
Authors: Bendejacq‐Seychelles Ana , Gibot‐Leclerc Stéphanie , Guillemin Jean‐Philippe , Mouille Gregory , Steinberg Christian
Published: October 2023

Among the alternatives to synthetic plant protection products, biocontrol appears as a promising method. This review reports on the diversity of fungal secondary metabolites phytotoxic to weeds and on the approach generally used to extract, characterize, identify and exploit them for weed management. The 183 phytotoxic fungal secondary metabolites discussed in this review fall into five main classes of molecules: 61 polyketides, 53 terpenoids, 36 nitrogenous metabolites, 18 phenols and phenolic acids, and 15 miscellaneous. They are mainly produced by the genera Drechslera, Fusarium and Alternaria. The phytotoxic effects, more often described by the symptoms they produce on plants than by their mode of action, range from inhibition of germination to inhibition of root and vegetative growth, including tissue and organ alterations. The biochemical characterization of fungal secondary metabolites requires expertise and tools to carry out fungal cultivation and metabolite extraction, phytotoxicity tests, purification and fractionation of the extracts, and chemical identification procedures. Phytotoxicity tests are mainly carried out under controlled laboratory conditions (not always on whole plants), while effectiveness against targeted weeds and environmental impacts must be assessed in greenhouses and open fields. These steps are necessary for the formulation of effective, environment‐friendly fungal secondary metabolites‐derived bioherbicides using new technologies such as nanomaterials. © 2023 Society of Chemical Industry.
Reproductive behavior of fruit flies: courtship, mating, and oviposition
Authors: Li Xin‐lian , Li Dou‐dou , Cai Xin‐yan , Cheng Dai‐feng , Lu Yong‐yue
Published: October 2023

Many species of the Tephritidae family are invasive and cause huge damage to agriculture and horticulture, owing to their reproductive characteristics. In this review, we have summarized the existing studies on the reproductive behavior of Tephritidae, particularly those regarding the genes and external factors that are associated with courtship, mating, and oviposition. Furthermore, we outline the issues that still need to be addressed in fruit fly reproduction research. The review highlights the implications for understanding the reproductive behavior of fruit flies and discusses methods for their integrated management and biological control. © 2023 Society of Chemical Industry.
Apixaban and rivaroxaban's physiologically‐based pharmacokinetic model validation in hospitalized patients: A first step for larger use of a priori modeling approach at bed side
Authors: Terrier Jean , Gaspar Frédéric , Gosselin Pauline , Raboud Olivier , Lenoir Camille , Rollason Victoria , Csajka Chantal , Samer Caroline , Fontana Pierre , Daali Youssef , Reny Jean‐Luc ,   for the OptimAT study group
Published: October 2023

When used in real‐world conditions, substantial interindividual variations in direct oral anticoagulant (DOAC) plasma concentrations are observed for a given dose, leading to a risk of over‐ or under‐exposure and clinically significant adverse events. Physiologically‐based pharmacokinetic (PBPK) models could help physicians to tailor DOAC prescriptions in vulnerable patient populations, such as those in the hospital setting. The present study aims to validate prospectively PBPK models for rivaroxaban and apixaban in a large cohort of elderly, polymorbid, and hospitalized patients. In using a model of geriatric population integrating appropriate physiological parameters into models first optimized with healthy volunteer data, observed plasma concentration collected in hospitalized patients on apixaban (n = 100) and rivaroxaban (n = 100) were adequately predicted (ratio predicted/observed area under the concentration curve for a dosing interval [AUCtau] = 0.97 [0.96–0.99] geometric mean, 90% confidence interval, ratio predicted/observed AUCtau = 1.03 [1.02–1.05]) for apixaban and rivaroxaban, respectively. Validation of the present PBPK models for rivaroxaban and apixaban in in‐patients represent an additional step toward the feasibility of bedside use.
COVID‐19 in hematopoietic stem‐cell transplant recipients: A systematic review and meta‐analysis of clinical characteristics and outcomes
Authors: Randi Bruno Azevedo , Higashino Hermes Ryoiti , Silva Vinícius Ponzio da , Xavier Erick Menezes , Rocha Vanderson , Costa Silvia Figueiredo
Published: October 2023

Patients who undergo hematopoietic stem‐cell transplantation (HSCT) are more susceptible to developing severe forms of COVID‐19 with an increased risk of mortality. The aim of this study was to analyze, by performing a systematic review and meta‐analysis, all studies that evaluated COVID‐19 in HSCT adult recipients and present clinical characteristics and outcomes. Studies were eligible for inclusion if they: (I) described the clinical characteristics of COVID‐19 in adult (aged 18 years old or above) HSCT recipients; (II) described outcomes of COVID‐19 in this population, mainly lethality; (III) were full‐text articles. We searched MedLine, Embase, SCOPUS, LILACS and Web of Science for full‐text studies that evaluated COVID‐19 in adult HSCT patients until 26 Apr 2023. Two independent reviewers screened the articles and extracted the data. The Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Studies Reporting Prevalence Data was used to assess quality of the included studies. Meta‐analysis was performed and the pooled prevalence of severe/critical disease and of death with a 95% CI was calculated with the random‐effects model. Sixteen studies were included; seven (43.7%) were multicenter. Most of the studies were from Europe (37.5%). All of them had a low risk of bias using the JBI Checklist. A total of 1186 patients were included. Allogeneic HSCT patients were the majority in most studies, with a total of 861 patients (72.5%). The symptomatic rate was 79.4%. The pooled prevalence of severe/critical COVID‐19 was 24.0% (95% CI 0.13–0.36; I2 = 94%; n = 334/990). The pooled prevalence of death for the entire population was 17% (95% CI 0.13–0.22; I2 = 76%; n = 221/1117), 17% (95% CI 0.12–0.23; I2 = 67%; n = 152/822) for allogeneic‐HSCT and 14% (95% CI 0.08–0.22; I4 = 65%; n = 48/293) for autologous‐HSCT. In conclusion, frequently the infection of SARS‐CoV‐2 in HSCT was symptomatic and lethality is higher than in general population. Thus, it is essential to focus on the implementation of measures to mitigate the risk of SARS‐CoV‐2 infection in this population, as well as to carefully assess HSCT recipients who develop COVID‐19.
Variation of the rates of necrotising enterocolitis in the neonatal networks in England
Authors: Longford Nicholas T.
Published: October 2023

Necrotising enterocolitis is an oft‐fatal disease of the intestinal tract in neonates born prematurely and with low birthweight. We study the variation of its rates across the neonatal networks (groups of hospital‐based neonatal care units) in England. We illustrate the problematic nature of hypothesis testing for a key decision, which an analysis is meant to inform, and apply an approach based on decision theory. We emphasise the role of sensitivity analysis in dealing with the ambiguity encountered in the process of eliciting information about the perspective of the client or sponsor for whom the analysis is conducted. In the application based on a fiducial distribution, the likelihood is approximated by a linearising transformation of the score function. Copyright © 2017 John Wiley & Sons, Ltd.
Variable selection in the functional linear concurrent model
Authors: Goldsmith Jeff , Schwartz Joseph E.
Published: October 2023

We propose methods for variable selection in the context of modeling the association between a functional response and concurrently observed functional predictors. This data structure, and the need for such methods, is exemplified by our motivating example: a study in which blood pressure values are observed throughout the day, together with measurements of physical activity, location, posture, affect or mood, and other quantities that may influence blood pressure. We estimate the coefficients of the concurrent functional linear model using variational Bayes and jointly model residual correlation using functional principal components analysis. Latent binary indicators partition coefficient functions into included and excluded sets, incorporating variable selection into the estimation framework. The proposed methods are evaluated in simulations and real‐data analyses, and are implemented in a publicly available R package with supporting interactive graphics for visualization. Copyright © 2017 John Wiley & Sons, Ltd.
Surface Modification of Nickel Titanate Nanocubes with Ultra‐small Palladium and Platinum Nanocrystals to Promote Solar Hydrogen Generation under Visible Light
Authors: Moses Yilleng T. , Bastia Sweta , Kumar Niharika , Chaudhary Yatendra S.
Published: October 2023

Modification of nickel titanate nanocubes with metal nanocrystals is a viable approach to build a Schottky heterojunction for efficient hydrogen generation. The deconvoluted XPS spectrum of Pt 4 f (peaks at 72.0 and 75.5 eV corresponding to Pt° and Pt2+) and Pd 3d3/2 (335.4 and 336.7 eV corresponding to Pd° and Pd2+) and presence of lattice fringes in HRTEM at 2.19 Å of Pd°, reveal the formation of heterojunction in Pd−NiTiO3 and Pt−NiTiO3 nanocubes. The solar hydrogen generation investigation exhibits 2‐fold enhancement in HER (130 and 165 μmol g−1 h−1 while using Pt−NiTiO3 and Pd−NiTiO3, respectively) than that of bare NiTiO3 (88 μmol g−1 h−1). The creation of heterojunctions between titanates and metal nanoparticles, facilitating efficient transport of photo‐generated electron to empty or partially filled d or f orbitals of metals, thereby lowering electron‐hole recombination rate, as revealed by shorter average lifetime 29 ns (Pd−NiTiO3) than 64 ns (NiTiO3). Further, the unison of faster charge transfer kinetics as revealed by the Nyquist plot, more negative flatband potential (Efb −0.3 vs. RHE) leading to appropriate band bending, reduced overpotential requirement, higher oxygen vacancies (19.46 %) and uniform dispersion of metal atoms on NiTiO3 surfaces that are acting as trapping centers etc. are enabling improved hydrogen generation in the case of Pd−NiTiO3.
Cyclic‐Phenoxaphosphinine‐Based Mixed Phosphonium‐Iodonium Ylides with Electron‐Withdrawing Substituents – Synthesis and Structural Features
Authors: Nenashev Anton , Dospekhov Dmitrii , Zavaruev Mikhail , Potapov Ilia , Levina Irina , Roznyatovsky Vitaly , Mironov Andrey , Pisarev Sergey , Pavlova Anna , Podrugina Tatyana
Published: October 2023

A series of phosphonium ylides and mixed phosphonium‐iodonium ylides based on cyclic phenoxaphosphinine has been synthesized, representing a new structural type of ylides. The influence of the electron‐withdrawing substituents of various nature on the stability and physicochemical properties of phenoxaphosphonium ylides is discussed. Our findings reveal a progressive reduction in ylide stability as the carbonyl group is replaced first with a phosphonate group and then with a nitrile group. NMR data indicates that the presence of a cyclic phosphonium group results in a lowered energy barrier to rotation about the carbon‐carbon bond, both in phosphonium and mixed phosphonium‐iodonium ylides with α‐carboxyl substituents when compared to triarylphosphonium ylides. These experimental results are further supported and analyzed in the context of density functional theory (DFT) calculations.
Synthesis of Symmetrical Biaryls by Copper‐Catalysed Homocoupling of Aryltriazenes in Guanidinium Ionic Liquid
Authors: Anchi Athmanand , Kumar P Pavan , Kalkhambkar Rajesh G. , Naik Ravi S. , Adam Abdel Majid A. , Refat Moamen S. , Mohammed Alsuhaibani Amnah
Published: October 2023

An efficient, facile and practical protocol to synthesize various biaryl analogues by the homocoupling of aryl triazenes promoted by guanidinium ionic liquids via copper catalysis has been demonstrated. The three different guanidinium ILs has been employed as solvent/promoter. Several moderate to strong electron‐withdrawing groups and electron‐donating groups are well tolerated by this protocol. The predictive mechanism demonstrating the Cu‐catalytic cycle and role of GIL as promoter. This methodology provides the corresponding products in good yields under moderate reaction conditions with potential for recycling and reuse of the GIL solvent.
Efficient Self‐Assembly Preparation of 3D Carbon‐Supported Ti3C2Tx Hollow Spheres for High‐Performance Potassium Ion Batteries
Authors: Huang Wei , Ma Zenghui , Zhong Lu , Luo Ketong , Li Wei , Zhong Shengkui , Yan Dongliang
Published: October 2023

MXenes are considered a promising negative electrode material for potassium ion batteries (PIBs) in view of their low potassium ion diffusion barrier and excellent electrical conductivity. However, the stacking phenomenon in practical applications severely reduces their active surface and leads to slow K+ diffusion. Herein, a facile composite template method is proposed to construct stacking‐resistance 3D carbon‐supported Ti3C2Tx (3D‐C@Ti3C2Tx) hollow spheres. Due to the unique structure, when used as a negative electrode material, as‐prepared 3D‐C@Ti3C2Tx hollow spheres show not only improved rate capability with 160.4 mAh g−1 at 100 mA g−1 and 133.7 mAh g−1 at 500 mA g−1, but also stable cycling performance with 142.5 mAh g−1 specific capacity remained at 2 A g−1 after 4200 cycles. Furthermore, the full cells with 3D‐C@Ti3C2Tx anode can operate stably for 1000 cycles at 100 mA g−1. Moreover, the linear fit analysis demonstrates that 3D‐C@Ti3C2Tx hollow spheres have a fast and stable capacitive potassium storage mechanism. This method is simple and easy to implement, which provide a feasible path to solve the stacking problem of 2D materials.
Optimization of Mixed Micelles Based on Oppositely Charged Block Copolymers by Machine Learning for Application in Gene Delivery
Authors: Leer Katharina , Reichel Liên S. , Kimmig Julian , Richter Friederike , Hoeppener Stephanie , Brendel Johannes C. , Zechel Stefan , Schubert Ulrich S. , Traeger Anja
Published: October 2023

The COVID‐19 mRNA vaccines represent a milestone in developing non‐viral gene carriers, and their success highlights the crucial need for continued research in this field to address further challenges. Polymer‐based delivery systems are particularly promising due to their versatile chemical structure and convenient adaptability, but struggle with the toxicity‐efficiency dilemma. Introducing anionic, hydrophilic, or “stealth” functionalities represents a promising approach to overcome this dilemma in gene delivery. Here, two sets of diblock terpolymers are created comprising hydrophobic poly(n‐butyl acrylate) (PnBA), a copolymer segment made of hydrophilic 4‐acryloylmorpholine (NAM), and either the cationic 3‐guanidinopropyl acrylamide (GPAm) or the 2‐carboxyethyl acrylamide (CEAm), which is negatively charged at neutral conditions. These oppositely charged sets of diblocks are co‐assembled in different ratios to form mixed micelles. Since this experimental design enables countless mixing possibilities, a machine learning approach is applied to identify an optimal GPAm/CEAm ratio for achieving high transfection efficiency and cell viability with little resource expenses. After two runs, an optimal ratio to overcome the toxicity‐efficiency dilemma is identified. The results highlight the remarkable potential of integrating machine learning into polymer chemistry to effectively tackle the enormous number of conceivable combinations for identifying novel and powerful gene transporters.
Learning induces EPO/EPOr expression in memory relevant brain areas, whereas exogenously applied EPO promotes remote memory consolidation
Authors: Almaguer‐Melian William , Mercerón‐Martinez Daymara , Alberti‐Amador Esteban , Alacán‐Ricardo Laura , de Bardet Javier Curi , Orama‐Rojo Norma , Vergara‐Piña Arturo Ernesto , Herrera‐Estrada Idalia , Bergado Jorge A.
Published: October 2023

Memory and learning allow animals to appropriate certain properties of nature with which they can navigate in it successfully. Memory is acquired slowly and consists of two major phases, a fragile early phase (short‐term memory, <4 h) and a more robust and long‐lasting late one (long‐term memory, >4 h). Erythropoietin (EPO) prolongs memory from 24 to 72 h when animals are trained for 5 min in a place recognition task but not when training lasted 3 min (short‐term memory). It is not known whether it promotes the formation of remote memory (≥21 days). We address whether the systemic administration of EPO can convert a short‐term memory into a long‐term remote memory, and the neural plasticity mechanisms involved. We evaluated the effect of training duration (3 or 5 min) on the expression of endogenous EPO and its receptor to shed light on the role of EPO in coordinating mechanisms of neural plasticity using a single‐trial spatial learning test. We administered EPO 10 min post‐training and evaluated memory after 24 h, 96 h, 15 days, or 21 days. We also determined the effect of EPO administered 10 min after training on the expression of arc and bdnf during retrieval at 24 h and 21 days. Data show that learning induces EPO/EPOr expression increase linked to memory extent, exogenous EPO prolongs memory up to 21 days; and prefrontal cortex bdnf expression at 24 h and in the hippocampus at 21 days, whereas arc expression increases at 21 days in the hippocampus and prefrontal cortex.
Hepatic T‐cell lymphoma in a blue‐fronted Amazon parrot (Amazona aestiva) and subcutaneous T‐cell lymphoma in a grey parrot (Psittacus erithacus)
Authors: Wen Amanda H. C. , Comolli Jessica R. , Aguilar Laura A. B. , Caudill Megan N. , Carmichael K. Paige , Divers Stephen J.
Published: October 2023

T‐cell lymphoma was diagnosed in a mature blue‐fronted Amazon parrot (Amazona aestiva) and a mature grey parrot (Psittacus erithacus). The Amazon parrot was diagnosed with soft tissue sarcoma in the neck and T‐cell hepatic lymphoma. The sarcoma was surgically removed, but chemotherapy for the lymphoma was declined by the owner. This parrot survived 24 months without treatment until it was euthanased for dyspnoea, the cause of which was not investigated. The grey parrot was diagnosed with subcutaneous T‐cell lymphoma on the left side of the neck that likely originated from the thymus. The mass was surgically excised without complications. The bird remained healthy 24 months after diagnosis, at which point follow‐up was lost. This case series documents the clinical presentation and diagnostic workup of T‐cell lymphoma in two Psittacidae patients. In both cases, T‐cell lymphomas were confirmed by histological examination and CD3 immunohistochemistry.