bluuebunny/crossref_metadata_2025 huggingface dataset:
A Multifunctional Nanoplatform for Tumor‐Targeted Imaging and Enhanced Ferroptosis Therapy
Authors: Zhao Dan , Wu Min , Tian Yanan , Gao Lu , Wang Fu
Published: February 2023

With the advantages of ferroptosis therapy (FT) in solving the apoptotic resistance of tumors, a smart strategy based on the combination of glucose oxidase (GOx) and ferroptosis‐inducing nanoagents is proposed to boost the FT. However, most of the nanoagents remain limited in complex synthesis, poor targeting specificity, and unclarified biological mechanisms. Herein, a multifunctional nanoplatform based on fluorescent apoferritin‐gold nanoclusters combined with GOx (AFt‐AuNCs@GOx) is designed for tumor‐targeted imaging and FT. The results show that AFt‐AuNCs@GOx catalyze the generation of toxic ·OH from H2O2 supplied by GOx. Consequently, AFt‐AuNCs@GOx induce the enhanced ferroptosis effect in 4T1 cells. Additionally, the transcriptome assay of 4T1 cells identifies the differential expression genes related to ferroptosis process after AFt‐AuNCs@GOx treatment. Moreover, with the merit of intrinsic fluorescence, the biodistribution both in vitro and in vivo of AFt‐AuNCs@GOx can be effectively visualized. In vivo evidences reveal that AFt‐AuNCs@GOx have the desired efficacy of FT and excellent biosafety. Overall, the AFt‐AuNCs@GOx nanoplatform offer remarkable advantages in simple architecture, fluorescent imaging, precise targeting, and tumor inhibition. The exploration of the ferroptosis effect and biological mechanisms of AFt‐AuNCs@GOx, as well as its application in tumor therapy, can introduce a new insight into the field of ferroptotic nanomedicine.
Engineered Artificial Membraneless Organelles in Saccharomyces cerevisiae To Enhance Chemical Production
Authors: Zhou Pei , Liu Hui , Meng Xin , Zuo Huiyun , Qi Mengya , Guo Liang , Gao Cong , Song Wei , Wu Jing , Chen Xiulai , Chen Wei , Liu Liming
Published: February 2023

Microbial cell factories provide a green and sustainable opportunity to produce value‐added products from renewable feedstock. However, the leakage of toxic or volatile intermediates decreases the efficiency of microbial cell factories. In this study, membraneless organelles (MLOs) were reconstructed in Saccharomyces cerevisiae by the disordered protein sequence A‐IDPs. A regulation system was designed to spatiotemporally regulate the size and rigidity of MLOs. Manipulating the MLO size of strain ZP03‐FM, the amounts of assimilated methanol and malate were increased by 162 % and 61 %, respectively. Furthermore, manipulating the MLO rigidity in strain ZP04‐RB made acetyl‐coA synthesis from oxidative glycolysis change to non‐oxidative glycolysis; consequently, CO2 release decreased by 35 % and the n‐butanol yield increased by 20 %. This artificial MLO provides a strategy for the co‐localization of enzymes to channel C1 starting materials into value‐added chemicals.
Amphibian‐like Flexible Organic Crystal Optical Fibers for Underwater/Air Micro‐Precision Lighting and Sensing
Authors: Vinod Kumar Avulu , Rohullah Mehdi , Chosenyah Melchi , Ravi Jada , Venkataramudu Uppari , Chandrasekar Rajadurai
Published: February 2023

Visible light guiding optical fibers with underwater operational capability are highly desired for subaquatic communication and sensing technologies. Herein, we present mechanically flexible, blue‐violet fluorescent (4,4′‐bis(2,6‐di(1H‐pyrazol‐1‐yl)pyridin‐4‐yl)biphenyl) (BPP) crystal waveguides with high‐aspect ratio. These milli‐meter‐long BPP crystals guide light actively and passively in ambient and underwater conditions demonstrating their amphibian‐like character. Due to the crystal's high flexibility, the optical fiber's output light direction in submerged and ambient states can be altered mechanically for high‐precision lighting and sensing applications. The development of such multi‐environment‐compatible and mechanically flexible organic optical fibers acting as sensing materials possess enormous potential for short‐range underwater photonic technologies.
Synthesis of Multifluoromethylatedγ‐Sultines by a Photoinduced Radical Addition–Polar Cyclization
Authors: Li Helian , Zhang Yongxin , Yang Xiaoxiao , Deng Zhenxi , Zhu Zhimin , Zhou Pan , Ouyang Xinke , Yuan Yuting , Chen Xi , Yang Lingyue , Liu Meng , Shu Chao
Published: February 2023

Despite the significance of sultines in synthesis, medicine, and materials science, the chemistry of sultines has remained unexplored due to their inaccessibility. Herein, we demonstrate the development of a photoredox‐catalyzed multifluoromethyl radical addition/SO2incorporation/polar cyclization cascade approach to multifluoromethylatedγ‐sultines. The reactions proceed by single electron transfer induced multifluoromethyl radical addition to an alkene followed by SO2incorporation, and single‐electron reduction for polar 5‐exo‐tetcyclization. Key to the success of the protocol is the use of easily oxidizable multifluoroalkanesulfinates as bifunctional reagents. The reactions proceed with excellent functional‐group tolerance to deliverγ‐sultines in moderate to excellent yields.
Strukturelle und mechanistische Studien zur Substrat‐ und Stereoselektivität der Indol‐Monooxygenase VpIndA1: Neue Wege für biokatalytische Epoxidationen und Sulfoxidationen
Authors: Kratky Julia , Eggerichs Daniel , Heine Thomas , Hofmann Sarah , Sowa Philipp , Weiße Renato H. , Tischler Dirk , Sträter Norbert
Published: February 2023

Flavoprotein‐Monooxygenasen sind eine vielseitige Gruppe von Enzymen für biokatalytische Reaktionen. Die dazugehörigen Monooxygenasen der Gruppe E (GEMs) katalysieren enantioselektive Epoxidierungs‐ und Sulfoxidierungsreaktionen. In dieser Arbeit beschreiben wir die Kristallstruktur einer Indol‐Monooxygenase aus dem Bakterium Variovorax paradoxus EPS, einer GEM mit der Bezeichnung VpIndA1. Basierend auf Substratkomplexstrukturen produktiver Bindungsmodi und in Verbindung mit Kraftfeldberechnungen sowie durch schnelle Mischungskinetik zeigen wir die strukturelle Grundlage der Substrat‐ und Stereoselektivität auf. Die strukturbasierte Umgestaltung der Substrattasche führte zu Varianten mit neuer Substratselektivität (für die Sulfoxidation von Benzylphenylsulfid) oder mit stark erhöhter Stereoselektivität (von 35.1 % auf 99.8 % ee für die Herstellung von (1S,2R)‐Indenoxid). Diese erste Bestimmung des Substratbindungsmodus von GEMs in Verbindung mit der Untersuchung von Struktur‐Funktions‐Beziehungen öffnet die Tür für ein strukturbasiertes Design dieser leistungsstarken Biokatalysatoren.
A Zeolite‐Like Metal–Organic Framework Based Membrane for Reverse Selective Hydrogen Separation and Butane Isomer Sieving
Authors: Chernikova Valeriya , Shekhah Osama , Belmabkhout Youssef , Karunakaran Madhavan , Eddaoudi Mohamed
Published: February 2023

Here, the fabrication of a defect‐free membrane that is based on a zeolite‐like metal‐organic framework (ZMOF) with the underlying ana topology is reported. The unique ana‐ZMOF structure provides high degree of pore connectivity, which is reflected by the fast transport of gases. Prominently, it offers an optimum pore‐aperture size, affording notable sieving selectivity for butane/isobutane, and optimal pore energetics for reverse CO2/H2 separation. This emphasize the potential for the application of pure MOF membranes, paving the way to more sustainability of energy resources.
Development of a Non‐Directed Petasis‐Type Reaction by an Aromaticity‐Disrupting Strategy
Authors: Gonzalez Kevin J. , Rand Alexander W. , Stoltz Brian M.
Published: February 2023

The Petasis‐type reaction, which couples an imine and boronic acid, is an important tool for C−C bond formation in organic synthesis. However, the generality of this transformation has been limited by the requirement for a directing heteroatom to enable reactivity. Herein, we report the development of a non‐directed Petasis‐type reaction that allows for the coupling of trifluoroborate salts with α‐hydroxyindoles. By disrupting aromaticity to generate a reactive iminium ion, in conjunction with using trifluoroborate nucleophiles, the method generates a new C−C bond without the need for a directing group. This reaction is operationally simple, providing α‐functionalized indoles in up to 99 % yield using sp, sp2, and sp3‐hybridized trifluoroborate nucleophiles. Finally, this reaction is applied as a novel bioconjugation strategy to link biologically active molecules and toward the convergent synthesis of non‐natural heterodimeric bisindole alkaloid analogs.
Sequence distribution determination by SWAMP‐MS a systematic way of analyzing multiple fragmented polymers with mass spectrometry
Authors: Mengerink Ynze , Philipsen Harry , Jordens Jan , Mengerink Josh , van der Hoeven Rob , Peters Ron A. H.
Published: February 2023

A new method to determine the blockiness and especially the block length distribution (BLD) of copolymers is described. This Systematic Workflow to Analyze Multi‐fragmented Polymers with Mass Spectrometry (SWAMP‐MS) is developed to characterize the sequence distribution of synthetic polymers. Copolymerization of polyamide 4,6 and polyamide 4,10 is used as a model system. Supercharged polymer ions, generated by electrospray ionization, swamp the mass spectrum due to <1> different chemical related distributions (chain composition, end groups), <2> the number of repeating units, <3> the charge and adduct distribution, and <4> isotopes distribution. Without selecting specific substrate ions, MSMS will transform this total ion‐SWAMP into chemical rich information of the polymer backbone. The generated fragments contain up to 20 monomers. The reduction of blockiness is evaluated by the decreasing abundancy of specific ions originating from the starting polymers. Moreover, evaluation of all significant fragments and applying Monte Carlo simulations can rebuild the polymer backbone and generate sequence distributions of the copolymerized samples, which is currently still a holy grail in co‐chemical polymer analysis.
Effects of frankincense on experimentally induced renal stones in rats
Authors: Al‐Marhoon Mohamed S. , Al‐Harrasi Ahmed , Siddiqui Khurram , Ashique Mohammed , Ali Haytham , Ali Badreldin H.
Published: February 2023

Objectives

Frankincense (Luban) is a resin obtained from trees of genus Boswellia. The south of Oman hosts Boswellia sacra trees known to have many social, religious and medicinal uses. The anti‐inflammatory and therapeutic potential of Luban has recently attracted the interest of the scientific community. The aim is to study the efficacy of Luban water extract and its essential oils on experimentally induced renal stones in rats.

Materials and Methods

A rat model of urolithiasis induced by trans‐4‐hydroxy‐L‐proline (HLP) was used. Wistar Kyoto rats (27 males, 27 females) were randomly distributed into nine equal groups. Treatment groups were given Uralyt‐U (standard) or Luban (50, 100 and 150 mg/kg/day), starting Day 15 from HLP induction for a duration of 14 days. The prevention groups were given Luban in similar doses, starting Day 1 of HLP induction for 28 days. Several plasma biochemical and histological parameters were recorded. Data were analysed with GraphPad Software. Comparisons were performed by one‐way analysis of variance (ANOVA) and the Bonferroni test.

Results

The lithogenic effects of HLP, such as an increase in urine oxalate and cystine, an increase in plasma uric acid and an increase in kidney levels of calcium and oxalate, have all been best significantly reversed by the Luban dose of 150 mg/kg/day. The histological changes of HLP on the kidney tissue including calcium oxalate crystal formation, cystic dilatation, high degree of tubular necrosis, inflammatory changes, atrophy and fibrosis have also been ameliorated by Luban dose of 150 mg/kg/day.

Conclusion

Luban has shown a significant improvement in the treatment and prevention of experimentally induced renal stones, particularly at a dose of 150 mg/kg/day. Further studies on the effect of Luban in other animal models and humans with urolithiasis are warranted.
Laccase–luminol chemiluminescence system: an investigation of substrate inhibition
Authors: Sánchez‐Trasviña Calef , Galindo‐Estrada José Daniel , Tinoco‐Valencia Raunel , Serrano‐Carreón Leobardo , Rito‐Palomares Marco , Willson Richard C. , Mayolo‐Deloisa Karla
Published: February 2023

Chemiluminescence (CL) reactions are widely used for the detection and quantification of many types of analytes. Laccase has previously been proposed in CL reactions; however, its light emission behaviour has not been characterized. This study was conducted to characterize the laccase–luminol system, determine its kinetic parameters, and analyze the effects of protein and OHˉ concentration on the CL signal. Laccase from Coriolopsis gallica was combined with different concentrations of luminol (125 nM to 4 mM), and the enzyme kinetics were evaluated using diverse kinetic models. The laccase–luminol system was able to produce CL without an intermediate molecule, but it exhibited substrate‐inhibition behaviour. A two‐site random model was used and suggested that when the first luminol molecule was bound to the active site, laccase affinity for the second luminol molecule was increased. This inhibition effect could be avoided using a low luminol concentration. At 5 μM luminol concentration, 1 mg/ml (0.13 U) laccase is needed to achieve nearly 90% of the maximum CL signal, suggesting that the available luminol could not bind to all active sites. Furthermore, the concentration of NaOH negatively affected the CL signal. The laccase–luminol system represents an alternative to existing CL systems, with potential uses in molecular detection and quantification.
Black Titania and Niobia within Ten Minutes – Mechanochemical Reduction of Metal Oxides with Alkali Metal Hydrides
Authors: Michaely Anna , Janka Oliver , Gießelmann Elias C. J. , Haberkorn Robert , Wiedemann Haakon T. A. , Kay Christopher W. M. , Kickelbick Guido
Published: February 2023

Partially or fully reduced transition metal oxides show extraordinary electronic and catalytic properties but are usually prepared by high temperature reduction reactions. This study reports the systematic investigation of the fast mechanochemical reduction of rutile‐type TiO2 and H‐Nb2O5 to their partially reduced black counterparts applying NaH and LiH as reducing agents. Milling time and oxide to reducing agent ratio show a large influence on the final amount of reduced metal ions in the materials. For both oxides LiH shows a higher reducing potential than NaH. An intercalation of Li+ into the structure of the oxides was proven by PXRD and subsequent Rietveld refinements as well as 6Li solid‐state NMR spectroscopy. The products showed a decreased band gap and the presence of unpaired electrons as observed by EPR spectroscopy, proving the successful reduction of Ti4+ and Nb5+. Furthermore, the developed material exhibits a significantly enhanced photocatalytic performance towards the degradation of methylene blue compared to the pristine oxides. The presented method is a general, time efficient and simple method to obtain reduced transition metal oxides.
Stable hemiaminals from axially chiral pyridine compounds
Authors: Tuncel Senel Teke , Demir Ilke , Erdem Safiye Sağ , Dogan Ilknur
Published: February 2023

In this study, we have synthesized a series of 3‐(pyridin‐2‐yl)‐2‐(pyridin‐2‐ylimino)thiazolidin‐4‐ol derivatives regioselectively from 2‐iminothiazolidin‐4‐ones using LiAlH4 at room temperature. Due to the presence of the restricted rotation around the N3‐Caryl single bond, the formation of M/P isomers was observed. The OH group of the hemiaminal was found to orient itself on the same side with pyridyl nitrogen during this restricted rotation to form an intramolecular hydrogen bond, which was demonstrated by the computational DFT study. This orientation presumably inhibited the occurrence of dehydration and stabilized the molecule.
Multi‐agent reinforcement learning for process control: Exploring the intersection between fields of reinforcement learning, control theory, and game theory
Authors: Yifei Yue , Lakshminarayanan Samavedham
Published: February 2023

The application of reinforcement learning (RL) in process control has garnered increasing research attention. However, much of the current literature is focused on training and deploying a single RL agent. The application of multi‐agent reinforcement learning (MARL) has not been fully explored in process control. This work aims to: (i) develop a unique RL agent configuration that is suitable in a MARL control system for multiloop control, (ii) demonstrate the efficacy of MARL systems in controlling multiloop process that even exhibit strong interactions, and (iii) conduct a comparative study of the performance of MARL systems trained with different game‐theoretic strategies. First, we propose a design of an RL agent configuration that combines the functionalities of a feedback controller and a decoupler in a control loop. Thereafter, we deploy two such agents to form a MARL system that learns how to control a two‐input, two‐output system that exhibits strong interactions. After training, the MARL system shows effective control performance on the process. With further simulations, we examine how the MARL control system performs with increasing levels of process interaction and when trained with reward function configurations based on different game‐theoretic strategies (i.e., pure cooperation and mixed strategies). The results show that the performance of the MARL system is weakly dependent on the reward function configuration for systems with weak to moderate loop interactions. The MARL system with mixed strategies appears to perform marginally better than MARL under pure cooperation in systems with very strong loop interactions.
Buprenorphine opens up for easier access, creating hope for all patients
Authors: Knopf Alison
Published: February 2023

Late last year when President Biden signed the “omnibus” spending bill eliminating the X‐waiver and the patient caps for buprenorphine prescribers were thrilled. The American Society of Addiction Medicine (ASAM), which had fought hard for the changes, claimed that the X‐waiver, formerly required by the Drug Enforcement Administration, was a barrier to prescribing.
Effect of Chlorine Salts on TiC Coating Morphology and Bonding Strength of Diamond Surface in Molten Salt Reaction
Authors: Meng Jin , Huang Jie , Xu Xuelu
Published: February 2023

To obtain a high‐quality TiC coating on the diamond (D) surface and improve the interfacial properties of metal matrix composites, the optimized molten salt method is used to prepare TiC coatings on the D surface. The effects of NaCl, KCl, and NaCl–KCl molten salts on the uniformity, surface morphology, composition, and bonding ability of TiC coatings are investigated by scanning electron microscopy, energy‐dispersive X‐ray spectroscopy (EDS), X‐ray diffraction, and cold–hot cycling experiments. The results show that the boiling and pickling processes after the molten salt reaction can effectively remove the residual chloride salts and Ti powders to obtain clean TiC‐coated D. The TiC particles of the coating surfaces prepared by NaCl and KCl molten salts are finer and more uniform, which is due to their higher melting points and shorter real reaction time compared with NaCl–KCl mixed salts. The TiC coating prepared by KCl has the best bonding ability and can withstand 50 times as many cold–hot cycles due to its uniform fine deposition particles and appropriate thickness. And, during cold–hot cycles, it can be found that the TiC coating cracking and shedding occur primarily at the edges and corners of the D with internal thermal stress concentration.
Liquid‐based cytology for differentiating two cases of pemphigus vulgaris from oral squamous cell carcinoma
Authors: Maruyama Satoshi , Yamazaki Manabu , Abé Tatsuya , Kato Yusuke , Kano Hiroyuki , Sumita Yoshimasa , Tomihara Kei , Tanuma Jun‐ichi
Published: February 2023

Pemphigus vulgaris (PV) is a rare autoimmune disease characterized by blisters on the skin and mucous membrane. Since it often appears in the oral mucosa first, it may be diagnosed by oral mucosal cytology. Although the cytologic finding is characterized by acantholytic cells, that is, Tzanck cells, it is important to distinguish PV from neoplastic lesions of the oral mucosal epithelium, including differentiation from atypical parabasal/basal cells, which appear in squamous cell carcinoma (SCC). In this study, we examined the cellular findings in two cases of PV and a case of well‐differentiated SCC with loss of epithelial cell cohesion. The samples were prepared using liquid‐based cytology, which showed small round‐shaped and deeply stained atypical, orangeophilic keratinocytes not only in SCC but also in PV, which made differentiation between the two difficult. However, Tzanck cells found in PV differ from the deep atypical parabasal/basal cells of SCC, suggesting that the cell outline is indistinct and small protrusions and brush‐like structures are observed. This feature of Tzanck cells may be useful in cytological judgment.
Red‐winged blackbirds nesting nearer to yellow warbler and conspecific nests experience less brood parasitism
Authors: Lawson Shelby L. , Enos Janice K. , Gill Sharon A. , Hauber Mark E.
Published: February 2023

In functionally referential communication systems, the signaler's message intended for a conspecific receiver may be intercepted and used by a heterospecific eavesdropper for its own benefit. For example, yellow warblers (Setophaga petechia) produce seet calls to warn conspecifics of nearby brood parasitic brown‐headed cowbirds (Molothrus ater), and red‐winged blackbirds (Agelaius phoeniceus) eavesdrop on and recruit to seet calls to mob the brood parasites. Prior work found that warblers nesting closer to blackbirds were less likely to be parasitized, suggesting that blackbirds may even be the target of warbler's seet calls to assist with antiparasitic defense. Here we discovered for the reverse to apply too: blackbirds nesting closer to yellow warblers also experienced lower probability of brood parasitism. Concurrently, we also found that blackbirds nesting closer to other blackbirds also experience lower parasitism rates. Although these are strictly correlational results, they nonetheless suggest that blackbirds are better able to defend their nest against cowbirds when also listening to nearby warblers' referential alarm calls.
The relationship between adipokine levels and bone mass—A systematic review
Authors: Mangion Darren , Pace Nikolai P. , Formosa Melissa M.
Published: February 2023

Introduction

Adipose tissue is the source of a broad array of signalling molecules (adipokines), which mediate interorgan communication and regulate metabolic homeostasis. Alterations in adipokine levels have been causally implicated in various metabolic disorders, including changes in bone mass. Osteoporosis is the commonest progressive metabolic bone disease, characterized by elevated risk of fragility fractures as a result of a reduced bone mass and microarchitectural deterioration. The effects of different adipokines on bone mass have been studied in an attempt to identify novel modulators of bone mass or diagnostic biomarkers of osteoporosis.

Methods

In this review, we sought to aggregate and assess evidence from independent studies that quantify specific adipokines and their effect on bone mineral density (BMD).

Results

A literature search identified 57 articles that explored associations between different adipokines and BMD. Adiponectin and leptin were the most frequently studied adipokines, with most studies demonstrating that adiponectin levels are associated with decreased BMD at the lumbar spine and femoral neck. Conversely, leptin levels are associated with increased BMD at these sites. However, extensive heterogeneity with regards to sample size, characteristics of study subjects, ethnicity, as well as direction and magnitude of effect at specific skeletal anatomical sites was identified. The broad degree of conflicting findings reported in this study can be attributed several factors. These include differences in study design and ascertainment criteria, the analytic challenges of quantifying specific adipokines and their isoforms, pre‐analytical variables (in particular patient preparation) and confounding effects of co‐existing disease.

Conclusions

This review highlights the biological relevance of adipokines in bone metabolism and reinforces the need for longitudinal research to elucidate the causal relationship of adipokines on bone mass.
Evaluating programming that thinks and works politically: Challenges and emerging practice
Authors: Jacobstein David , Swift Sarah
Published: February 2023

Issues of power are not new to program evaluation. What is new is a consideration of how programming uses insights into incentives that shape and adapt implementation. How should one evaluate in a way that explicitly assesses the ways in which a program considers power? One of the innovative topics deriving from the democracy and governance space is the approach of thinking and working politically (TWP) which is seeing increased use in development programming. TWP suggests different mental models and practical approaches to achieving development objectives in ways that are more contextually grounded and informed by power dynamics. This article describes several of the core challenges to evaluation of TWP and also a rubric of considerations for more effective evaluation practices in this emerging field.
Challenging democracy, human rights, and governance evaluation capacity development through a transformative lens
Authors: Olavarria Claudia , Mertens Donna M.
Published: February 2023

Democracy, human rights, and governance (DRG) evaluation practice faces diverse challenges, not only because of the complexity of intervention designs and implementation but also due to the complexity of the fragile contexts in which DRG evaluation is generally applied. Evaluating in fragile contexts demands responsiveness to the complexity and provides challenges to define what capacities and competencies a DRG evaluator should have. In 2019, the International Organization for Cooperation in Evaluation (IOCE) was funded to design a set of tools to develop individual and institutional DRG evaluation capacities in an online training course and an associated toolkit. These materials aim to advocate for more DRG evaluation for a stronger democracy, advancing human rights, and increased governance. Using a transformative lens, this chapter critically reviews the challenges and constraints faced while developing DRG evaluators’ capacities. This critical analysis of complexity with a transformative lens adds insights into the practice of evaluation in the pursuit of human rights and social, economic, and environmental justice.
Overexpression of MrEsa1 accelerated growth, increased ascospores yield, and the polyketide production in Monascus ruber
Authors: Zhang Jing , Shao Yanchun , Chen Fusheng
Published: February 2023

Esa1 has been proven to be an important histone acetyltransferase involved in the regulation of growth and metabolism. Monascus spp. with nearly 2000 years of edible history in East Asian countries can produce a variety of polyketides. It is unknown whether Esa1 plays a regulatory role in Monascus spp. In this study, we isolated the homology of histone acetyltransferase Esa1 (named MrEsa1) and constructed a mresa1‐overexpressed strain. Western blot experiments showed that MrEsa1 hyperacetylated at K4 and K9 of the H3 subunit in Monascus ruber. Overexpression of mresa1 led to the larger colony diameter and increased dry cell mass; meanwhile, the conidia germination rate was significantly accelerated in the mresa1‐overexpressed strain before 4 h, and the number of ascospores in the mresa1‐overexpressed strain was significantly higher than that in WT. In addition, the Monascus azaphilone pigments (MonAzPs) and citrinin production of the mresa1‐overexpressed strain were 1.7 and 2.4 times more than those of WT, respectively. Reverse transcription‐quantitative polymerase chain reaction experiment suggested that mrpigB, mrpigH, mrpigJ, and mrpigK, involved in MonAzPs synthesis, and pksCT, mrl3, and mrl7, involved in citrinin synthesis, were upregulated in mresa1‐overexpressed strain. This study provides important insights into the effect of MrEsa1 on the developmental process and the production of secondary metabolites in Monascus spp.
Conversion to AbobotulinumtoxinA Increases Waning Time and Efficacy for Cervical Dystonia
Authors: Samotus Olivia , Jog Mandar
Published: February 2023

Background

Symptom re‐emergence before re‐injection negatively impacts cervical dystonia (CD) patients receiving botulinum toxin type A (BoNT‐A) therapy. Longer waning time is associated with abobotulinumtoxinA (abo‐BoNT‐A) as compared to onabotulinumtoxinA (ona‐BoNT‐A)/incobotulinumtoxinA (inco‐BoNT‐A) formulations.

Objectives

To compare waning time and treatment outcomes when chronically injected CD patients experiencing early waning despite being optimized on BoNT‐A (ona‐BoNT‐A/inco‐BoNT‐A) were converted to abo‐BoNT‐A.

Methods

Thirty‐three chronically injected CD participants with a waning time of ≤8 weeks were converted to abo‐BoNT‐A (1:2.5 dose ratio) for three injections every 12‐weeks. The second and third injection patterns were kinematically optimized. Participants were converted back to their original BoNT‐A for the fourth injection (1:2.5) using the same third abo‐BoNT‐A pattern. Participant‐perceived waning times were collected post‐injections. Clinical scales (Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)) and kinematic measures were collected 12‐weeks post‐injection and at three peak effect time‐points.

Results

Compared to baseline, waning time (12–22 days) significantly increased following all abo‐BoNT‐A treatments (P < 0.005) but was not significantly different at the fourth injection (original BoNT‐A reconversion). TWSTRS sub‐scores significantly reduced following all abo‐BoNT‐A treatments (P < 0.0001) and at peak effect following the third injection compared to original BoNT‐A. Dysphagia and muscle weakness were reported and comparable to safety of original BoNT‐A formulations.

Conclusions

Optimized patients experiencing waning had significant improvement in the peak benefit as well as the duration of effect when converted to abo‐BoNT‐A. This effect was toxin dependent as reconversion to the original BoNT‐A using the kinematically optimized pattern failed to produce an improvement in waning.
Multiple slot modules for high field magnetic resonance imaging array coils
Authors: Alkandari Dheyaa , Bosshard John C. , Huang Chung‐Huan , Wright Steven M.
Published: February 2023

Purpose

Mitigating coupling effects between coil elements represents a continuing challenge. Here, we present a 16‐bowtie slot volume coil arranged in eight independent dual‐slot modules without the use of any decoupling circuits.

Methods

Two electrically short “bowtie” slot antennas were used to form a “module.” A bowtie configuration was chosen because electromagnetic modeling results show that bowtie slots exhibit improved efficiency when compared to thin rectangular slots. An eight‐module volume coil was evaluated through electromagnetic modeling, bench tests, and MRI experiments at 4.7 T.

Results

Bench tests indicate that worst‐case coupling between modules did not exceed −14.5 dB. MR images demonstrate well‐localized patterns about single excited modules confirming the low coupling between modules. Homogeneous MR images were acquired from a synthesized quadrature birdcage transmit mode. MRI experiments show that the RF power requirements for the proposed coil are 9.2 times more than a birdcage coil. Whereas from simulations performed to assess the proposed coil losses, the total power dissipated in the phantom was 1.1 times more for the birdcage. Simulation results at 7 T reveal an equivalent B1+ homogeneity when compared with an eight‐dipole coil.

Conclusion

Although exhibiting higher RF power requirements, as a transmit coil when the power availability is not a restriction, the inherently low coupling between electrically short slots should enable the use of many slot elements around the imaging volume. The slot module described in this paper should be useful in the design of multi‐channel transmit coils.
Retrospective motion correction through multi‐average k‐space data elimination (REMAKE) for free‐breathing cardiac cine imaging
Authors: Neofytou Alexander Paul , Neji Radhouene , Kowalik Grzegorz Tomasz , Mooiweer Ronald , Wong James , Fotaki Anastasia , Ferreira Joana , Evans Carl , Bosio Filippo , Mughal Nabila , Razavi Reza , Pushparajah Kuberan , Roujol Sébastien
Published: February 2023

Purpose

To develop a motion‐robust reconstruction technique for free‐breathing cine imaging with multiple averages.

Method

Retrospective motion correction through multiple average k‐space data elimination (REMAKE) was developed using iterative removal of k‐space segments (from individual k‐space samples) that contribute most to motion corruption while combining any remaining segments across multiple signal averages. A variant of REMAKE, termed REMAKE+, was developed to address any losses in SNR due to k‐space information removal. With REMAKE+, multiple reconstructions using different initial conditions were performed, co‐registered, and averaged. Both techniques were validated against clinical “standard” signal averaging reconstruction in a static phantom (with simulated motion) and 15 patients undergoing free‐breathing cine imaging with multiple averages. Quantitative analysis of myocardial sharpness, blood/myocardial SNR, myocardial‐blood contrast‐to‐noise ratio (CNR), as well as subjective assessment of image quality and rate of diagnostic quality images were performed.

Results

In phantom, motion artifacts using “standard” (RMS error [RMSE]: 2.2 ± 0.5) were substantially reduced using REMAKE/REMAKE+ (RMSE: 1.5 ± 0.4/1.0 ± 0.4, p < 0.01). In patients, REMAKE/REMAKE+ led to higher myocardial sharpness (0.79 ± 0.09/0.79 ± 0.1 vs. 0.74 ± 0.12 for “standard”, p = 0.004/0.04), higher image quality (1.8 ± 0.2/1.9 ± 0.2 vs. 1.6 ± 0.4 for “standard”, p = 0.02/0.008), and a higher rate of diagnostic quality images (99%/100% vs. 94% for “standard”). Blood/myocardial SNR for “standard” (94 ± 30/33 ± 10) was higher vs. REMAKE (80 ± 25/28 ± 8, p = 0.002/0.005) and tended to be lower vs. REMAKE+ (105 ± 33/36 ± 12, p = 0.02/0.06). Myocardial‐blood CNR for “standard” (61 ± 22) was higher vs. REMAKE (53 ± 19, p = 0.003) and lower vs. REMAKE+ (69 ± 24, p = 0.007).

Conclusions

Compared to “standard” signal averaging reconstruction, REMAKE and REMAKE+ provide improved myocardial sharpness, image quality, and rate of diagnostic quality images.
The impact of remote consultations on the health and wellbeing of first contact physiotherapists in primary care: A mixed methods study
Authors: Anchors Zoe , Jones Bethan , Thomas Rachel , Berry Alice , Walsh Nicola
Published: February 2023

Background

First Contact Physiotherapists (FCPs) were introduced to reduce demands on GPs by providing improving access to expert musculoskeletal care. FCPs experience similar workplace stressors to GPs and there is an emerging concern that remote consultations are causing further impacts to their wellbeing.

Aim

To explore the impact of remote consultations on FCPs.

Methods

A mixed methods sequential explanatory study with FCPs was conducted. An online survey measured the usage and impact of remote consultations. Semi‐structured interviews explored the lived experiences of using remote consultations.

Results

The online survey was completed by 109 FCPs. A key benefit of remote consultations was patient convenience; perceived challenges included IT issues, poor efficacy, FCP anxiety, isolation, and increased workload. FCPs viewed remote consultations as a ‘challenge’ rather than a ‘threat’. Nearly two thirds of the FCPs had not received relevant training, yet over half were interested. Follow‐up interviews with 16 FCPs revealed 4 themes: (1) Remote consultations provide logistical benefits to the patient; (2) Compromised efficacy is the key challenge of remote consultations; (3) Challenges for FCPs working in areas of high deprivation; and (4) Remote consultations impact the health, wellbeing and work satisfaction of FCPs.

Conclusions

Remote consultations offer a convenient alternative for patients, but may add to FCP stress particularly in areas of high socioeconomic deprivation. Further research is required to understand how remote consultations can be enhanced when communication barriers and lower levels of digital literacy exist. Continued monitoring of job satisfaction and resilience levels is important to ensure FCPs remain in their role.
Identification of Degenerated Murine Facial Nerves With Fluorescence Labeling After Transection Injury
Authors: Crawford Kayva L. , Lee Yu‐Jin , Hom Marisa , Rosenthal Eben L. , Orosco Ryan K. , Nguyen Quyen T.
Published: February 2023

Objective

Delayed peripheral nerve repair is complicated by nerve degeneration and atrophy that can prevent identification. We use a murine facial nerve transection model to demonstrate the efficacy of ALM‐488 (bevonescein) in labeling degenerated facial nerves with quantitative image analysis and qualitative survey data.

Study Design

Prospective cohort study.

Setting

Laboratory.

Methods

Ten wild‐type mice underwent transection of the lower facial nerve division with subsequent degeneration. Either 9 (n = 5 mice) or 12 (n = 5 mice) weeks later, mice underwent intravenous infusion of ALM‐488 with in vivo real‐time fluorescence imaging (FL) of the facial nerve. Using ImageJ, the mean gray value of each nerve segment under white light reflectance (WLR) and FL was compared to that of adjacent soft tissue to calculate the signal‐to‐background ratio (SBR). A survey was distributed to evaluate the perceived utility of ALM‐488 in surgeon identification of degenerated nerves.

Results

The mean SBR of degenerated nerves was 1.08 (standard deviation [SD]: 0.07) under WLR and 2.11 (SD: 0.31) under FL (p < 0.001). In mice with degenerated nerves, survey participants identified on average 3.01 (SD: 1.84) nerve branches under WLR and 5.73 (SD: 1.88) under FL (p < 0.0001). Under FL, 47 of 48 survey responses correctly identified isolated, degenerated nerves; in contrast, only 12 responses identified degenerated nerves under WLR (p < 0.0001).

Conclusion

Preoperative intravenous infusion of ALM‐488 with FL improves the identification of degenerated facial nerves. ALM‐488 also improves surgeon confidence in nerve identification, particularly in degenerated nerve branches that are not visible with WLR.
Endoscopically assisted bone lid surgery for foreign body removal from the maxillary sinus and maxillary bone
Authors: Takaoka Shohei , Uchida Fumihiko , Ishibashi‐Kanno Naomi , Yamagata Kenji , Yanagawa Toru , Bukawa Hiroki
Published: February 2023

Background

Bone lid surgery (BLS) is commonly used for the removal of foreign bodies from the maxillary sinus.

Case presentation

Imaging tests showed the presence of a foreign body in the maxillary bone, close to the maxillary sinus floor, and in the maxillary sinus. Removal of this foreign body was performed using endoscopically assisted BLS. Rough areas distinctly different from the surrounding bone were detected via endoscopy was removed.

Conclusion

We assessed the effectiveness of endoscopically assisted BLS in the removal of foreign bodies from the maxillary sinus and maxillary bone.
Non‐typhoidal Salmonella bacteremia in a healthy young man after a maxillary cystectomy: A case report
Authors: Yoshitomi Izumi , Kawasaki Goro
Published: February 2023

Background

Non‐typhoidal Salmonella (NTS) is a major cause of infectious diarrhea worldwide. Although NTS bacteremia is frequently observed in immunocompromised hosts, it rarely occurs in healthy subjects.

Case presentation

We report a case in which a 15‐year‐old male was diagnosed with NTS bacteremia after undergoing an operation. He had a high temperature on the 6th postoperative day but did not exhibit any obvious gastrointestinal manifestations. A blood culture was positive for NTS. Cefotaxime was intravenous, and the patient's symptoms improved.

Conclusion

We experienced a case of non‐typhoidal Salmonella (NTS), which is rare in healthy individuals.
Assessing the value of biodiversity‐specific footprinting metrics linked to South American soy trade
Authors: Molotoks Amy , Green Jonathan , Ribeiro Vivian , Wang Yunxia , West Chris
Published: February 2023

International demand for a small handful of commodities is a major driver of tropical deforestation and associated biodiversity loss. Previous commitments to reduce commodity‐driven deforestation have largely failed, yet there are currently various proposals in place globally, which aim to address the challenge of reducing overseas environmental impacts of supply chains.

However, many of these are highly focused on the issue of deforestation alone. Given that biodiversity objectives are often cited alongside protection of forests, deforestation rates are therefore often used as a proxy for biodiversity loss. Assessments exploring deforestation risk linked to commodity supply chains, enabled by increasingly granular information on sourcing patterns, therefore potentially overlook other important biodiversity concerns.

In response, we examine sourcing risks across three producer countries in South America for both forest loss and biodiversity for the example of soy production and trade, which has one of the largest embodied deforestation footprints in international supply chains. Using IUCN and Birdlife data, we create four simple biodiversity metrics to represent different aspects of species‐related biodiversity risk and link both these, and a forest loss metric representing soy driven deforestation, to sub‐national supply chain data to examine risks for the two largest importers from each producer country.

We find relatively little evidence of convergence between forest loss and biodiversity metrics, as well as divergence between the four biodiversity indicators both for different importers and across landscapes. This suggests not only that forest loss alone is unlikely to be an adequate proxy for biodiversity, especially at larger spatial scales when considering risks across sourcing patterns, but also that further work is necessary to develop a deeper understanding of interactions between more complex measures of biodiversity and their consequences for informing supply chain activities.

Read the free Plain Language Summary for this article on the Journal blog.
Experiments and simulations on cookoff characteristics of a DNAN based cast explosive
Authors: Wang Xinjie , You Sa , Liu Ruifeng , Bai Mengjing , Duan Zhuoping , Huang Fenglei
Published: February 2023

Incidents caused by fire and combat operations can heat energetic materials that may lead to thermal explosion and result in structural damage and casualty, thus understanding the response of energetic materials to thermal insults is crucial for the safety design and assessment of insensitive munitions. In the present work, cookoff characteristics of a new DNAN‐based cast explosive ROL‐1 are systematically analyzed. Small‐scale slow cookoff experiments were performed and an overall reaction kinetic model including the melt‐ignition model for DNAN was developed and implemented in FLUENT. The simulated results agree well with the experimental data, which verifies the validity of the model. The large‐scale fast cookoff experiment and simulation were then performed. Ignition behaviors as well as the reaction mechanism of ROL‐1 under slow and fast cookoffs are investigated. The heat generation rates are highly correlated to the temperature gradient, liquid phase fraction, and ignition behaviors in ROL‐1. The ignition of ROL‐1 happens at around 550 K, delaying the ignition temperature of the HMX (493 K) by nearly 60 K, indicating the potential substitution of NTO for HMX. The safety of ROL‐1 has proven to stand out in comparison to a range of mixed explosives.
A case of prolonged COVID‐19 treated with tixagevimab/cilgavimab
Authors: Shimizu Takahiro , Shirasaki Hiroki , Okafuji Kazuhiro , Sawazaki Aiko , Iwabuchi Tasuku , Matubayashi Ryo
Published: February 2023

A 54‐year‐old woman presented to our hospital with a fever and cough. The patient had a medical history of follicular lymphoma treated with obinutuzumab. She was infected with an omicron variant of coronavirus disease 2019 and developed viral pneumonia. Antibiotics, molnupiravir, sotrovimab, and prednisolone were administered but were ineffective. The patient's symptoms and pneumonia persisted. She could not produce antibodies against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) because she was administered obinutuzumab. Finally, when we administered 300 mg of tixagevimab and cilgavimab, pneumonia immediately improved. However, the infection was prolonged for more than 4 months. Patients treated with anti‐CD20 monoclonal antibodies may have a prolonged SARS‐CoV‐2 infection. In such cases, tixagevimab/cilgavimab may be effective.
A Depth-Bounded Semantics for Becoming Informed
Authors: Larotonda Marco , Primiero Giuseppe
Published: February 2023

We present the three-valued modal logic DBBL-BI$$_{n}$$ to formally express information transmission among ordered agents bounded by limited access to repositories and where secrecy is admissible, viz. agents are not forced to transmit every data they possess to everyone else. The language, along with standard formulae for information holding at reachable states, includes formulae for agent and group information transmission, as well as assertion of trustworthy information. The description of information accessibility and transmission among agents is represented by formulae that hold in virtue of two distinct kinds of relations. We illustrate the application of the formal system with some intuitive examples.
Islet Autoantibody Standardization Program: interlaboratory comparison of insulin autoantibody assay performance in 2018 and 2020 workshops
Authors: Marzinotto Ilaria , Pittman David L. , Williams Alistair J. K. , Long Anna E. , Achenbach Peter , Schlosser Michael , Akolkar Beena , Winter William E. , Lampasona Vito ,   participating laboratories
Published: February 2023

Aims/hypothesis

The Islet Autoantibody Standardization Program (IASP) aims to improve the performance of immunoassays measuring autoantibodies in type 1 diabetes and the concordance of results across laboratories. IASP organises international workshops distributing anonymised serum samples to participating laboratories and centralises the collection and analysis of results. In this report, we describe the results of assays measuring IAA submitted to the IASP 2018 and 2020 workshops.

Methods

The IASP distributed uniquely coded sera from individuals with new-onset type 1 diabetes, multiple islet autoantibody-positive individuals, and diabetes-free blood donors in both 2018 and 2020. Serial dilutions of the anti-insulin mouse monoclonal antibody HUI-018 were also included. Sensitivity, specificity, area under the receiver operating characteristic curve (ROC-AUC), partial ROC-AUC at 95% specificity (pAUC95) and concordance of qualitative/quantitative results were compared across assays.

Results

Results from 45 IAA assays of seven different formats and from 37 IAA assays of six different formats were submitted to the IASP in 2018 and 2020, respectively. The median ROC-AUC was 0.736 (IQR 0.617–0.803) and 0.790 (IQR 0.730–0.836), while the median pAUC95 was 0.016 (IQR 0.004–0.021) and 0.023 (IQR 0.014–0.026) in the 2018 and 2020 workshops, respectively. Assays largely differed in AUC (IASP 2018 range 0.232–0.874; IASP 2020 range 0.379–0.924) and pAUC95 (IASP 2018 and IASP 2020 range 0–0.032).

Conclusions/interpretation

Assay formats submitted to this study showed heterogeneous performance. Despite the high variability across laboratories, the in-house radiobinding assay (RBA) remains the gold standard for IAA measurement. However, novel non-radioactive IAA immunoassays showed a good performance and, if further improved, might be considered valid alternatives to RBAs.

Graphical abstract