bluuebunny/crossref_metadata_2025 huggingface dataset:
Real‐life benefits of intrajejunal levodopa infusion therapy in four patients with the parkinsonian variant of progressive supranuclear palsy: A 1‐year follow‐up data report
Authors: Metta Vinod , Chaudhuri K. Ray , Leta Valentina , Mridula Kandadai Rukmini , Koduri Chaitanya , Deepak Sai , Kalpala Rakesh , Reddy Nageswar , Chung‐Faye Guy , Borgohain Rupam
Published: August 2022

Background

Progressive supranuclear palsy (PSP) is a progressive neurodegenerative condition presenting with different clinical endophenotypes. The parkinsonian variant of PSP (PSP‐P) is characterised by early but fading responsiveness to high‐dose levodopa therapy; however, high‐dose oral therapy is often associated with intolerance due to dopaminergic side effects and so doses may have to be capped despite clinical benefits. Evidence from animal models and real‐life registries suggest far higher doses of levodopa can be tolerated if given in a continuous drug delivery (CDD) manner. We investigated tolerance and possible clinical benefits in patients with PSP‐P still responsive to levodopa after initiating CDD in the form of intrajejunal levodopa infusion (IJLI) therapy as part of a compassionate usage program (CU).

Methods

This is an observational clinical data report from the IJLI implementation program undertaken in regional tertiary referral Parkinson's centres in India and at King's College Hospital London, Dubai as part of a CU. Four patients with PSP‐P receiving IJLI as a part of a CU underwent evaluations of liver and renal function, motor and nonmotor function, quality of life, sleep dysfunction, fatigue, anxiety and depression, and cognitive impairment at baseline and 6 and 12 months post‐IJLI initiation.

Results

In total, three out of four patients successfully completed 12 months of treatment (6 months in one patient). All four patients showed good tolerability to IJLI even at higher doses (1400 and 1960 mg at 6 and 12 months, respectively) when compared to oral levodopa (812.5 ± 103 levodopa equivalent daily dose [LEDD]) and presented with overall persistent improvements in motor and nonmotor scores and quality‐of‐life scores at 6 and 12 months post‐IJLI. All patients showed improvement in estimated glomerular filtration rate (43.50 ml/min/1.73 m2 to 67.5 ml/min/1.73 m2 and 79.5 ml/min/1.73 m2 at 6 and 12 months, respectively).

Conclusions

IJLI led to persistent beneficial effects on motor and some nonmotor aspects in patients with PSP‐P at up to 12 months after treatment with associated improvement in overall renal function.
Diffusion tensor imaging studies on subjects with suicidal thoughts and behaviors: A descriptive literature review
Authors: Zanghì Emanuele , Corallo Francesco , Lo Buono Viviana
Published: August 2022

Objective

Globally, suicide represents the second leading cause of death in young people aged 15–29 years for both sexes, after traffic accidents. Suicide occurs not only in high‐income countries, in high‐income countries but it is a global phenomenon in all regions of the world and it represents a serious public health problem.

Method

This review was conducted on studies focused on white matter alterations in people who have attempted or thought about suicide. We searched PubMed and Scopus databases and screened references of included studies and reviewed articles for additional citations. From the initial 21 publications, we included only 12 studies that met search criteria and described the association between white matter alterations and suicide.

Results

White matter alterations in suicidal behaviors were found in the prefrontal cortex, orbitofrontal cortex, internal capsule, corpus callosum, and default mode networks, which are critical cerebral areas involved in emotion processing and regulation, decision‐making, executive functions, and empathy.

Conclusions

White matter alteration in cerebral areas involving high cognitive process and emotional regulation to confer a heightened vulnerability for suicidal behavior. Suicide is a complex process ranging from suicidal ideation to planning, attempting, or committing suicide. The identification of abnormalities in underlying neural circuitry may help delineate the neurobiological basis for suicide risk.
Density and porosity optimization of graphene monoliths with high mass‐loading for high‐volumetric‐capacitance electrodes
Authors: Wang Dongliang , Sheng Lizhi , Jiang Meihui , Jin Xin , Lin Xinru , Lee Sang‐Young , Shi Junyou , Chen Wenshuai
Published: August 2022

Improving the volumetric capacitance of graphene materials for supercapacitors without sacrificing their rate capability, especially at high mass‐loading, is a challenge because of the sluggish electrochemical kinetics of compact graphene electrodes. Here, a compact graphene monolith (dense graphene ribbons [DGRs]‐0.6) was fabricated by using graphene oxide ribbons as building blocks and deliberately harmonizing the graphene primitive unit structure and interlayer spacing. The DGRs‐0.6 contained abundant oxygen‐containing functional groups and a highly interconnected pore structure, resulting in a large ion‐accessible surface area, a high packing density, and fast electron/ion transport pathways. The DGRs‐0.6 electrode exhibited a volumetric capacitance of 316 F cm–3, a rate capability of 220 F cm–3 at 100 A g–1, and ultralong cycling stability. For a mass loading of 11 mg cm−2, the DGRs‐0.6 delivered volumetric capacitances of 150 F cm−3 at 1 A g−1 and 109 F cm−3 at 50 A g−1. The good rate capability and volumetric capacitance of DGRs‐0.6 under high mass loading demonstrate its potential as a supercapacitor electrode for practical applications.
Anthropocentric, biospheric and egobiocentric environmental values and green product purchase intention: The mediating effect of environmental identity
Authors: Perera Chamila R. , Kalantari Daronkola Hassan , Johnson Lester W.
Published: August 2022

This study investigates how the relationship between environmental values (anthropocentric, biospheric and egobiocentric) and green product purchase intention is mediated by environmental identity. Asurvey conducted online involving 564 Australians informs the findings. Data analysis is performed using AMOS, a structural equation modelling package. Out of the three environmental values, egobiocentric values have the strongest influence on environmental identity followed by anthropocentric values, whilst biospheric values do not affect environmental identity. Whilst environmental identity fully mediates the relationship between anthropocentric and egobiocentric values and green product purchase intention, it does not mediate the relationship between biospheric values and green product purchase intention. Biospheric values have a direct relationship with green product purchase intention. The study provides valuable insights on developing green marketing strategies by revealing that unlike individuals with anthropocentric and egobiocentric values, individuals with biospheric values cannot be promoted to purchase green products as a form of environmental identity expression.
Hypertrophic lichen planus on lip mimicking SCC
Authors: Mozafari Nikoo , Bidari‐Zerehpoosh Farahnaz , Movahedi Mahdiyeh , Dadkhahfar Sahar
Published: August 2022

The lichen planus (LP) is an inflammatory and immune‐mediated disorder that can affect the hair, mucous membranes, nails, and skin. Lichen planus rarely affects the lips. In cases of lip involvement, it presents as radiated streaks, lace‐like papules, and erosions. There is no report of lip LP presenting as hypertrophic plaque. Here, we report interesting and rare clinical presentations of LP in a 45‐year‐old male patient that presented with a verrucous hyperkeratotic plaque on the lower lip mimicking squamous cell carcinoma. However, oral examination revealed, reticulated white patches on the bilateral buccal mucosa, and a biopsy of the lip lesion revealed lichenoid dermatitis which led to the diagnosis of hypertrophic lichen planus. Familiarity with the different clinical presentations of LP and its variants is essential for prompt diagnosis and effective treatment.
Electronic and ionic properties of sintered cathode of LiNi0.6Mn0.2Co0.2O2 (NCM622)
Authors: Waetzig Katja , Huettl Juliane , Goedeke Dieter , Schilm Jochen , Nikolowski Kristian , Partsch Mareike
Published: August 2022

Li‐ion solid‐state batteries have the potential for high energy densities and improved safety. Oxidic all solid‐state batteries require co‐sintering of the Li‐ion conductive solid electrolyte, the active electrode material, and an electronic conductive additive to give a composite electrode. A first step for the realization of this complex system is the study of the sintering behavior of the active material itself as a single‐phase component and to investigate the electrochemical activity as well as the electronic properties after heat treatment. In this study monolithic NCM622 cathodes with a thickness of about 90 μm were sintered at temperatures up to 900°C by using a low‐melting glass as sintering additive. For these ceramic cathodes sintered at T = 800°C, an electronic conductivity of 3.0 × 10–3 S cm–1 and six orders of magnitude lower Li‐ion conductivity of about 10–9 S cm–1 were determined by DC conductivity measurement. To investigate the electrochemical performance of the sintered cathode material, the porous microstructure was infiltrated with liquid electrolyte and a charging capacity of 140 mAh g–1 (92% of the theoretical capacity) was measured with C/50 cycling rate. In comparison, the electrochemical performance without infiltration of a Li‐ion conductive liquid was tested with polyethylene oxide as polymeric separator. With these measurements the ability of the sintered cathode to charge/discharge as well as to provide sufficient high electronic conductivity has been demonstrated.
Point‐to‐face contact heterojunctions: Interfacial design of 0D nanomaterials on 2D g‐C3N4 towards photocatalytic energy applications
Authors: Tan Xin‐Quan , Ng Sue‐Faye , Mohamed Abdul Rahman , Ong Wee‐Jun
Published: August 2022

Green energy generation is an indispensable task to concurrently resolve fossil fuel depletion and environmental issues to align with the global goals of achieving carbon neutrality. Photocatalysis, a process that transforms solar energy into clean fuels through a photocatalyst, represents a felicitous direction toward sustainability. Eco‐rich metal‐free graphitic carbon nitride (g‐C3N4) is profiled as an attractive photocatalyst due to its fascinating properties, including excellent chemical and thermal stability, moderate band gap, visible light‐active nature, and ease of fabrication. Nonetheless, the shortcomings of g‐C3N4 include fast charge recombination and limited surface‐active sites, which adversely affect photocatalytic reactions. Among the modification strategies, point‐to‐face contact engineering of 2D g‐C3N4 with 0D nanomaterials represents an innovative and promising synergy owing to several intriguing attributes such as the high specific surface area, short effective charge‐transfer pathways, and quantum confinement effects. This review introduces recent advances achieved in experimental and computational studies on the interfacial design of 0D nanostructures on 2D g‐C3N4 in the construction of point‐to‐face heterojunction interfaces. Notably, 0D materials such as metals, metal oxides, metal sulfides, metal selenides, metal phosphides, and nonmetals on g‐C3N4 with different charge‐transfer mechanisms are systematically discussed along with controllable synthesis strategies. The applications of 0D/2D g‐C3N4‐based photocatalysts are focused on solar‐to‐energy conversion via the hydrogen evolution reaction, the CO2 reduction reaction, and the N2 reduction reaction to evaluate the photocatalyst activity and elucidate reaction pathways. Finally, future perspectives for developing high‐efficiency 0D/2D photocatalysts are proposed to explore potential emerging carbon nitride allotropes, large‐scale production, machine learning integration, and multidisciplinary advances for technological breakthroughs.
Palladium‐Catalyzed Arylfluorination of Alkenes: A Powerful New Approach to Organofluorine Compounds
Authors: Remete Attila Márió , Nonn Melinda , Kiss Loránd
Published: August 2022

Fluorine incorporation into organic molecules is often beneficial to their absorption, distribution, metabolism, and excretion (ADME) properties or bioactivity. As a consequence, organofluorine compounds have become quite common amongst drugs and agrochemicals, and their preparation is a highly important topic in both synthetic organic chemistry and pharmaceutical chemistry. One of the newly developed methods for accessing organofluorine compounds is Pd‐catalyzed arylfluorination of alkenes. It is an olefin difunctionalization process that simultaneously introduces an aryl group and a fluorine atom into an alkene framework. This review provides a concise overview of this powerful and versatile method.
OER‐073: A multicenter phase 2 study evaluating the role of pazopanib in angiosarcoma
Authors: Thiebaud Julio Alvarenga , Ravi Vinod , Litwin Samuel , Schuetze Scott M. , Movva Sujana , Agulnik Mark , Kraft Andrew S. , Tetzlaff Eric D. , Somaiah Neeta , von Mehren Margaret
Published: August 2022

Background

Angiosarcomas are rare mesenchymal sarcomas that can present as primary cutaneous or noncutaneous disease. They express a variety of vascular endothelial growth factor receptors. The authors hypothesized that the treatment of angiosarcoma with pazopanib, a multikinase inhibitor with activity against vascular endothelial growth factor receptors, would result in disease response and prolonged disease stabilization.

Methods

This was an open‐label, phase 2 trial of pazopanib in patients who had incurable angiosarcoma. The co‐primary end points were response according to the Response Evaluation Criteria in Solid Tumors and progression‐free survival (PFS) at 3 months. The starting dose of pazopanib was 800 mg daily.

Results

Twenty‐nine patients were accrued between 2011 and 2018, and 22 patients were evaluable for response. Toxicities were similar to those identified in prior reports. There was one partial response (3%), and the clinical benefit rate (including complete responses, partial responses, and stable disease) was 48%, which was observed more frequently in patients who had cutaneous disease. The median PFS was 14.4 weeks, and the 3‐month PFS rate determined by Kaplan–Meier estimate was 54.6% (95% CI, 36.0%–82.9%), meeting the primary study objective. The Kaplan–Meier overall survival estimate was 16.1 months.

Conclusions

Pazopanib therapy in patients who had incurable angiosarcoma was associated with meaningful disease control, especially in those who had cutaneous disease with limited objective responses.

Lay Summary

Angiosarcoma is a rare cancer that can be found on the skin or in internal organs.

This study tested pazopanib, an oral targeted medication, to determine its benefit in patients with angiosarcoma who could not undergo the removal of their tumors by surgery.

Pazopanib treatment was safe, and no new side effects were reported.

The study showed that pazopanib controlled tumor growth in one half of patients at 3 months and was more common in angiosarcomas of the skin; it led to tumor shrinkage in a minority of patients (1 of 29).
A distributed self‐organising node deployment algorithm for mobile sensor networks
Authors: Sadeghi Ghahroudi Mahsa , Shahrabi Alireza , Boutaleb Tuleen
Published: August 2022

Providing the appropriate coverage is quite essential for the effective functioning of many applications in Wireless Sensor Networks. Therefore, the efficiency of node deployment algorithms to supply the requested coverage is of high significance. In this paper, inspired by the equilibrium of molecules, a novel node deployment algorithm, called Smart Self‐organising Node Deployment (SSND), is proposed to provide maximum coverage. Despite other proposed algorithms, which provide coverage based on the collective movement of nodes with massive energy consumption, SSND moves one sensor in every neighbourhood at each step to reduce the sensor nodes' movement and hence the energy consumption. The chosen sensor nodes at each time step are distributedly determined by an eligibility function to reduce the non‐essential movements while improving the accuracy of the reported locations of neighbours. Our extensive simulation study shows that SSND can achieve up to 30%coverage improvement compared to those of other algorithms in most scenarios and provides an adequate trade‐off between coverage and energy consumption.
Cutaneous melanoma: An update on pathogenesis, prevention, and treatment
Authors: Frech Fabio S. , Bommareddy Kanthi , Hernandez Loren , Dreyfuss Isabella , Urbonas Rebecca , Nouri Keyvan
Published: August 2022

Although the cause for the rise in melanoma incidence remains a topic of debate, its potentially aggressive nature necessitates a continual update on the pathophysiologic mechanisms of disease and current guidelines for management. Akin to other cutaneous malignancies, sun exposure remains a crucial risk factor in the development of different melanoma subtypes. There are specific non‐UV associated mutations that are commonly found in most melanomas and some nevi, such as B‐RAF V600E, that may represent an initial insult of a multistep process that eventually leads to progression of the lesion into a more aggressive phenotype. The standard of care for early melanoma management remains surgical excision with wide margins, however management changes with more advanced lesions by the addition of imaging, sentinel lymph node biopsies, genetic testing, immune, and targeted therapy. Different novel treatment regimens for advanced unresectable melanomas are being investigated with the use of targeted therapies and vaccines. Novel screening technology using artificial intelligence for detection of melanoma is currently being developed but remains in its early stages with its effectiveness being significantly lower compared to clinicians. As such, melanoma prevention and early detection through skin examinations remain crucial to avoid potentially deadly complications from more advanced lesions.
Selective Cyclopropanation/Aziridination of Olefins Catalyzed by Bis(pyrazolyl)borate Cu(I) Complexes
Authors: Zhao Qianyi , Yao Qiu‐Yue , Zhang Yan‐Jiao , Xu Ting , Zhang Jie , Chen Xuenian
Published: August 2022

Bis(pyrazolyl)borate complexes [BBN(pzR)2]Cu(I) were evaluated as catalysts in the reaction of carbene/nitrene transfer and addition to C=C bonds of a wide range of aromatic, heterocyclic and aliphatic olefins. The complexes exhibit high catalytic efficiency and selectivity in both processes.
AOP Report: Thyroperoxidase Inhibition Leading to Altered Visual Function in Fish Via Altered Retinal Layer Structure
Authors: Gölz Lisa , Baumann Lisa , Pannetier Pauline , Braunbeck Thomas , Knapen Dries , Vergauwen Lucia
Published: August 2022

Thyroid hormones (THs) are involved in the regulation of many important physiological and developmental processes, including vertebrate eye development. Thyroid hormone system–disrupting chemicals (THSDCs) may have severe consequences, because proper functioning of the visual system is a key factor for survival in wildlife. However, the sequence of events leading from TH system disruption (THSD) to altered eye development in fish has not yet been fully described. The development of this adverse outcome pathway (AOP) was based on an intensive literature review of studies that focused on THSD and impacts on eye development, mainly in fish. In total, approximately 120 studies (up to the end of 2021) were used in the development of this AOP linking inhibition of the key enzyme for TH synthesis, thyroperoxidase (TPO), to effects on retinal layer structure and visual function in fish (AOP-Wiki, AOP 363). In a weight-of-evidence evaluation, the confidence levels were overall moderate, with ample studies showing the link between reduced TH levels and altered retinal layer structure. However, some uncertainties about the underlying mechanism(s) remain. Although the current weight-of-evidence evaluation is based on fish, the AOP is plausibly applicable to other vertebrate classes. Through the re-use of several building blocks, this AOP is connected to the AOPs leading from TPO and deiodinase inhibition to impaired swim bladder inflation in fish (AOPs 155–159), together forming an AOP network describing THSD in fish. This AOP network addresses the lack of thyroid-related endpoints in existing fish test guidelines for the evaluation of THSDCs. Environ Toxicol Chem 2022;41:2632–2648. © 2022 SETAC
Fish Embryo Acute Toxicity Testing and the RTgill-W1 Cell Line as In Vitro Models for Whole-Effluent Toxicity (WET) Testing: An In Vitro/In Vivo Comparison of Chemicals Relevant for WET Testing
Authors: Scott Justin , Grewe Ryan , Minghetti Matteo
Published: August 2022

The fathead minnow (Pimephales promelas) fish embryo acute toxicity (FET) test was compared to the fish gill cells (RTgill-W1) in vitro assay and to the fish larvae acute toxicity test to evaluate their sensitivity for whole-effluent toxicity (WET) testing. The toxicity of 12 chemicals relevant for WET testing was compared as proof of principle. The concentrations lethal to 50% of a population (LC50) of embryos were compared to those in fish larvae and to the 50% effect concentration (EC50) in RTgill-W1 cells from previous literature. Along with traditional FET endpoints (coagulation, somite development, tail detachment, and heartbeat), cardiotoxicity was evaluated for WET applicability. Heart rate was measured at LC20 and LC50 values of six subselected chemicals (Cd, Cu, Ni, ammonia, 3,4-dichloraniline, and benzalkonium chloride). In addition, the toxicity of Cd and Ni was evaluated in RTgill-W1 cells exposed in a hypoosmotic medium to evaluate the effect that osmolarity may have on metal toxicity. A significant correlation was found between the FET and larvae LC50 values but not between the RTgill-W1 EC50 and FET LC50 values. Although sensitivity to Ni and Cd was found to increase with hypoosmotic conditions for FET and RTgill-W1 cells, a correlation was only found with removal of Ni from the analysis. Hypoosmotic conditions increased sensitivity with a significant correlation between RTgill-W1 cells and larvae. Cardiotoxicity was shown in three of the five subselected chemicals (Cd, Cu, and 3,4-dichloroaniline). Overall, both in vitro alternative models have shown good predictability of toxicity in fish in vivo for WET chemicals of interest. Environ Toxicol Chem 2022;41:2721–2731. © 2022 SETAC
Profiling of syngeneic mouse HCC tumor models as a framework to understand anti–PD‐1 sensitive tumor microenvironments
Authors: Zabransky Daniel J. , Danilova Ludmila , Leatherman James M. , Lopez‐Vidal Tamara Y. , Sanchez Jessica , Charmsaz Soren , Gross Nicole E. , Shin Sarah , Yuan Xuan , Hernandez Alexei , Yang Hongqui , Xavier Stephanie , Shu Daniel , Saeed Ali , Munjal Kabeer , Kamdar Zeal , Kagohara Luciane T. , Jaffee Elizabeth M. , Yarchoan Mark , Ho Won Jin
Published: August 2022

Background and Aims:

The treatment of hepatocellular carcinoma (HCC) has been transformed by the use of immune checkpoint inhibitors. However, most patients with HCC do not benefit from treatment with immunotherapy. There is an urgent need to understand the mechanisms that underlie response or resistance to immunotherapy for patients with HCC. The use of syngeneic mouse models that closely recapitulate the heterogeneity of human HCC will provide opportunities to examine the complex interactions between cancer cells and nonmalignant cells in the tumor microenvironment.

Approach and Results:

We leverage a multifaceted approach that includes imaging mass cytometry and suspension cytometry by time of flight to profile the tumor microenvironments of the Hep53.4, Hepa 1‐6, RIL‐175, and TIBx (derivative of TIB‐75) syngeneic mouse HCC models. The immune tumor microenvironments vary across these four models, and various immunosuppressive pathways exist at baseline in orthotopic liver tumors derived from these models. For instance, TIBx, which is resistant to anti–programmed cell death protein 1 therapy, contains a high proportion of “M2‐like” tumor‐associated macrophages with the potential to diminish antitumor immunity. Investigation of The Cancer Genome Atlas reveals that the baseline immunologic profiles of Hep53.4, RIL‐175, and TIBx are broadly representative of human HCCs; however, Hepa 1‐6 does not recapitulate the immune tumor microenvironment of the vast majority of human HCCs.

Conclusions:

There is a wide diversity in the immune tumor microenvironments in preclinical models and in human HCC, highlighting the need to use multiple syngeneic HCC models to improve the understanding of how to treat HCC through immune modulation.
Injectable hydrogel as a carrier of vancomycin and a cathelicidin‐derived peptide for osteomyelitis treatment
Authors: Machado Alexandra , Pereira Isabel , Silva Vanessa , Pires Isabel , Prada Justina , Poeta Patrícia , Costa Luís , Pereira José Eduardo , Gama Miguel
Published: August 2022

A local drug delivery system that attempts to find a suitable balance between antimicrobial and regenerative actions was developed for osteomyelitis treatment (OM). This system combines the angiogenic and immunomodulatory peptide LLKKK18 (LL18) and vancomycin hydrochloride (VH), loaded into an injectable oxidized dextrin (ODEX)‐based hydrogel (HG). In vitro cytotoxicity was analyzed in MC3T3‐E1 pre‐osteoblasts and erythrocytes. The kinetics of LL18 release was studied. Antimicrobial activity was assessed in vitro against a clinical Methicillin‐Resistant Staphylococcus aureus (MRSA) strain. A rat model of acute OM was developed by direct inoculation into a tibia defect, concomitantly with the implantation of the drug‐loaded HG. The local bioburden was quantified and damage in surrounding tissues was examined histologically. In vitro, ODEX‐based HG displayed a safe hemolytic profile. Half of LL18 (53%) is released during the swelling phase at physiological pH, then being gradually released until complete HG degradation. LL18‐loaded HG at 300 μM was the most effective peptide formulation in decreasing in vivo infection among concentrations ranging from 86 to 429 μM. The histopathological scores observed in vivo varied with the LL18 concentration in a dose‐dependent manner. VH at 28 mM completely eradicated bacteria, although with substantial tissue injury. We have found that sub‐millimolar doses of VH combined with LL18 at 300 μM may suffice to eradicate the infection, with reduced tissue damage. We propose an easy‐to‐handle, shape‐fitting HG formulation with the potential to treat MRSA‐infected bone with low VH doses associated with LL18.
Hexokinase 2: The preferential target of trehalose‐6‐phosphate over hexokinase 1
Authors: Magalhães Rayne S. S. , Boechat Fernanda C. , Brasil Aline A. , Neto José. R. M. , Ribeiro Gabriela D. , Paranhos Luan H. , Neves de Souza Natália , Vieira Tuane , Outeiro Tiago F. , Neves Bianca C. , Eleutherio Elis C. A.
Published: August 2022

Cancer‐related metabolic features are in part maintained by hexokinase 2 upregulation, which leads to high levels of glucose‐6‐phosphate (G6P) and is needed to provide energy and biomass to support rapid proliferation. Using a humanized model of the yeast Saccharomyces cerevisiae, we explored how human hexokinase 2 (HK2) behaves under different nutritional conditions. At high glucose levels, yeast presents aerobic glycolysis through a regulatory mechanism known as catabolic repression, which exerts a metabolic adaptation like the Warburg effect. At high glucose concentrations, HK2 did not translocate into the nucleus and was not able to shift the metabolism toward a highly glycolytic state, in contrast to the effect of yeast hexokinase 2 (Hxk2), which is a crucial protein for the control of aerobic glycolysis in S. cerevisiae. During the stationary phase, when glucose is exhausted, Hxk2 is shuttled out of the nucleus, ceasing catabolic repression. Cells harvested at this condition display low glucose consumption rates. However, glucose‐starved cells expressing HK2 had an increased capacity to consume glucose. In those cells, HK2 localized to mitochondria, becoming insensitive to G6P inhibition. We also found that the sugar trehalose‐6‐phosphate (T6P) is a human HK2 inhibitor, like yeast Hxk2, but was not able to inhibit human HK1, the isoform that is ubiquitously expressed in almost all mammalian tissues. In contrast to G6P, T6P inhibited HK2 even when HK2 was associated with mitochondria. The binding of HK2 to mitochondria is crucial for cancer survival and proliferation. T6P was able to reduce the cell viability of tumor cells, although its toxicity was not impressive. This was expected as cell absorption of phosphorylated sugars is low, which might be counteracted using nanotechnology. Altogether, these data suggest that T6P may offer a new paradigm for cancer treatment based on specific inhibition of HK2.
Prediction of self‐diffusion coefficients of chemically diverse pure liquids by all‐atom molecular dynamics simulations
Authors: Baba Hiromi , Urano Ryo , Nagai Tetsuro , Okazaki Susumu
Published: August 2022

Molecular self‐diffusion coefficients underlie various kinetic properties of the liquids involved in chemistry, physics, and pharmaceutics. In this study, 547 self‐diffusion coefficients are calculated based on all‐atom molecular dynamics (MD) simulations of 152 diverse pure liquids at various temperatures employing the OPLS4 force field. The calculated coefficients are compared with experimental data (424 extracted from the literature and 123 newly measured by pulsed‐field gradient nuclear magnetic resonance). The calculations well agree with the experimental values. The determination coefficient and root mean square error between the observed and calculated logarithmic self‐diffusion coefficients of the 547 entries are 0.931 and 0.213, respectively, demonstrating that the MD calculation can be an excellent industrial tool for predicting, for example, molecular transportation in liquids such as the diffusion of active ingredients in biological and pharmaceutical liquids. The self‐diffusion coefficients collected in this study are compiled into a database for broad researches including artificial intelligence calculations.
Asymmetric depth‐filtration: A versatile and scalable method for high‐yield isolation of extracellular vesicles with low contamination
Authors: Chernyshev Vasiliy S. , Chuprov‐Netochin Roman N. , Tsydenzhapova Ekaterina , Svirshchevskaya Elena V. , Poltavtseva Rimma A. , Merdalimova Anastasiia , Yashchenok Alexey , Keshelava Amiran , Sorokin Konstantin , Keshelava Varlam , Sukhikh Gennadiy T. , Gorin Dmitry , Leonov Sergey , Skliar Mikhail
Published: August 2022

We developed a novel asymmetric depth filtration (DF) approach to isolate extracellular vesicles (EVs) from biological fluids that outperforms ultracentrifugation and size‐exclusion chromatography in purity and yield of isolated EVs. By these metrics, a single‐step DF matches or exceeds the performance of multistep protocols with dedicated purification procedures in the isolation of plasma EVs. We demonstrate the selective transit and capture of biological nanoparticles in asymmetric pores by size and elasticity, low surface binding to the filtration medium, and the ability to cleanse EVs held by the filter before their recovery with the reversed flow all contribute to the achieved purity and yield of preparations. We further demonstrate the method's versatility by applying it to isolate EVs from different biofluids (plasma, urine, and cell culture growth medium). The DF workflow is simple, fast, and inexpensive. Only standard laboratory equipment is required for its implementation, making DF suitable for low‐resource and point‐of‐use locations. The method may be used for EV isolation from small biological samples in diagnostic and treatment guidance applications. It can also be scaled up to harvest therapeutic EVs from large volumes of cell culture medium.
Flavor differences of soybean and defatted soybean fermented soy sauce and its correlation with the enzyme profiles of the kojis
Authors: Tian Yi‐Fan , Chen Yu‐Xing , Tong Xing , Hou Sha , Zhao Mou‐Ming , Feng Yun‐Zi
Published: August 2022

BACKGROUND

Soybeans and defatted soybeans, commonly used as protein ingredients, have different flavors of their fermented soy sauce. Clarifying the differences between the two soy sauces, as well as the formation mechanism, is an important prerequisite for improving the flavor of defatted soybean soy sauce. To this goal, the aroma characteristics of two soy sauces and their volatile profiles were compared by sensory evaluation and gas chromatography‐mass spectrometry, and eight enzyme activities and volatile profiles of matured koji were determined.

RESULTS

Sensory results showed that the acids, fruity and cooked potato‐like attributes were higher in whole soybean fermented soy sauce, whereas defatted soybean soy sauce exhibited higher smoky and malty attributes, closely related to the contents of aroma‐active compounds in soy sauce, such as isobutyl acetate, 2/3‐methylbutanal, acetic acid and 2/3‐methylbutanoic acid. The content of most volatiles in the matured kojis showed a consistent trend with that of soy sauce: alcohols, acids, furan(one)s and ketones. Interestingly, acid protease and cellulase activities were 3.3 and 1.6 times higher in the whole soybean koji than in defatted soybean koji, respectively, whereas neutral protease, aminopeptidase, glucoamylase and β‐glucosidase were approximately 2.0 times higher in defatted soybean koji.

CONCLUSION

In summary, the flavor differences between soybean and defatted soybean fermented soy sauce were not only caused by the differences in the content of flavor precursors in the materials, but also closely related to the differences in the enzymatic profiles accumulated during the koji‐making process. © 2022 Society of Chemical Industry.
Presence of a resident species aids invader evolution
Authors: Lachapelle Josianne , Bestion Elvire , Jackson Eleanor E. , Schaum C.‐Elisa
Published: August 2022

Interactions between phytoplankton species shape their physiological and evolutionary responses. Yet, studies addressing the evolutionary responses of phytoplankton in changing environments often lack an explicit element of biotic interactions. Here, we ask (1) how the presence of a locally adapted phytoplankton species will affect an invading phytoplankton species' evolutionary response to a physiologically challenging environment; (2) whether this response is conserved across environments varying in quality; and (3) which traits are associated with being a successful invader under climate change scenarios. In a conceptual first step to disentangle these broad questions, we experimentally evolved populations of fresh‐ and seawater phytoplankton in a novel salinity (the freshwater green algae Chlamydomonas in salt water, and the marine Ostreococcus in freshwater), either as mono‐cultures (colonizers) or as co‐cultures (invaders: invading a novel salinity occupied by a resident species, for example, Chlamydomonas invading salt water occupied by resident Ostreococcus) for 200 generations. We superimposed a temperature treatment (control (22°C), mild warming (26°C), drastic warming (32°C), and fluctuating (22°C/32°C) warming) as a representative aspect of climate change with the potential to ameliorate or deteriorate existing environmental conditions. Invaders had systematically lower extinction rates and evolved overall higher growth rates, as well as broader salinity and temperature preferences than colonizers. The invading species' evolutionary responses differed from those of colonizers in a replicable way across environments of differing quality. The evolution of small cell size and high reactive oxygen species tolerance may explain the invaders' higher fitness under the scenarios tested here.
Transmission Laser Welding of Similar and Dissimilar Semiconductor Materials
Authors: Sopeña Pol , Wang Andong , Mouskeftaras Alexandros , Grojo David
Published: August 2022

Laser micro‐welding is an advanced manufacturing method today applied in various domains. However, important physical limitations have prevented so far to demonstrate its applicability in silicon (Si) and other technology‐essential semiconductors. Concentrating on circumventing the optical limits on the deliverable energy density at interfaces between narrow‐gap materials with intense infrared light, the first feasibility demonstration of transmission laser welding between Si workpieces using nanosecond laser pulses is made. A shear joining strength of 32 ± 10 MPa which compares very favorably to the complex process alternatives is obtained. Supported by experiments repeated on different material combinations including gallium arsenide, it is confirmed that this remarkable performance level is achievable for similar and dissimilar semiconductors. The demonstrations rely on a small footprint fiber laser, an aspect that holds great promises for the advent of a high‐efficiency flexible process beneficial for important technology developments including lab‐on‐a‐chip and hybrid semiconductor systems.
Printed Polymer‐Stabilized Chiral Nematic Liquid Crystal Privacy Windows
Authors: Li Mengmeng , Kamal Waqas , Orr Andrew C. J. , Castrejón‐Pita Alfonso A. , Elston Steve J. , Morris Stephen M.
Published: August 2022

In this paper, drop‐on‐demand (DoD) printing is demonstrated of polymer stabilized chiral nematic liquid crystal (PSCLC) privacy windows that can function in either a conventional mode (scattering to transparent) or reverse mode (transparent to scattering) with the application of an electric field. Inkjet printed droplets of the PSCLC mixture, with diameters of the order of 100–200 µm and sandwiched in LC layer thicknesses of ≈10–15 µm, are characterized in terms of their transmission as a function of the electric field amplitude and the response times for switching into and out of the scattering state. The results show that the printed droplets, and arrays thereof, exhibit similar electro‐optical properties to analogous thin‐film devices, but with the ability to incorporate bespoke features such as images and decorative patterns. Finally, the electro‐optical switching of a printed PSCLC privacy window whereby alphanumeric characters can be made to appear and disappear with the application of an electric field is demonstrated.
Exploration of the interchromosomal effects in preimplantation genetic testing for structural rearrangements based on next‐generation sequencing
Authors: Fan Junmei , Zhang Xueluo , Chen Yanhua , Zhang Junkun , Zhang Lei , Bi Xingyu , Wang Jinbao , Huang Xiang , Yan Meiqin , Wu Xueqing
Published: August 2022

Background

To investigate the interchromosomal effect (ICE) in chromosome translocation carriers.

Methods

Data on preimplantation genetic testing aneuploidy and structural rearrangements (translocation) were retrospectively collected and classified into a reciprocal translocation group, a Robertsonian translocation group and a control group. According to the carrier's gender and age, all cases underwent further subgroup difference analysis of de novo abnormal embryo rates and the number of chromosomes involved in de novo abnormal embryos.

Results

Among the 283 couples who participated in this study, 1076 blastocysts from 352 cycles were collected, and 246 de novo abnormal embryos were included. There was a significant difference in the rate of de novo abnormal embryos among the three groups (p < .05) but no significant difference in the number of de novo abnormal chromosomes in the abnormal embryos (p > .05). Gender and age (classified by 35 years old) had no effect on the de novo abnormal embryo ratios among the translocation carriers (p > .05). However, the de novo abnormal ratio increased with age. The embryo constitution reflected no significant difference between the translocation groups (p > .05).

Conclusion

The ICE was detected for the translocation carriers. The de novo abnormal embryo ratio increased with age. Gender had no effect on the de novo abnormal embryo ratio. Translocation status played a more important role than age and gender.
A novel Methylomirabilota methanotroph potentially couples methane oxidation to iodate reduction
Authors: Zhu Baoli , Karwautz Clemens , Andrei Stefan , Klingl Andreas , Pernthaler Jakob , Lueders Tillmann
Published: August 2022

Impact statement

Methane oxidizing microbes play a key role in reducing the emission of this potent greenhouse gas to the atmosphere. The known versatility of the recently discovered anaerobic Methylomirabilota methanotrophs is limited. Here, we report a novel uncultured Methylomirabilis species, Candidatus Methylomirabilis iodofontis, with the genetic potential of iodate respiration from biofilm in iodine‐rich cavern spring water. Star‐like cells resembling Methylomirabilis oxyfera were directly observed from the biofilm and a high‐quality metagenome‐assembled genome (MAG) of Ca. M. iodofontis was assembled. In addition to oxygenic denitrification and aerobic methane oxidation pathways, the M. iodofontis MAG also indicated its iodate‐reducing potential, a capability that would enable the bacterium to use iodate other than nitrite as an electron acceptor, a hitherto unrecognized metabolic potential of Methylomirabilota methanotrophs. The results advance the current understanding of the ecophysiology of anaerobic Methylomirabilota methanotrophs and may suggest an additional methane sink, especially in iodate‐rich ecosystems.
Design of a filtration system to improve the dose distribution of an accelerator‐based neutron capture therapy system
Authors: Hu Naonori , Tanaka Hiroki , Ono Koji
Published: August 2022

Purpose

The aim of this study is to design and evaluate a neutron filtration system to improve the dose distribution of an accelerator‐based neutron capture therapy system.

Methods

An LiF‐sintered plate composed of 99%‐enriched 6Li was utilized to filter out low‐energy neutrons to increase the average neutron energy at the beam exit. A 5‐mm thick filter to fit inside a 12‐cm diameter circular collimator was manufactured, and experimental measurements were performed to measure the thermal neutron flux and gamma‐ray dose rate inside a water phantom. The experimental measurements were compared with the Monte Carlo simulation, particle, and heavy ion transport code system. Following the experimental verification, three filter designs were modeled, and the thermal neutron flux and the biologically weighted dose distribution inside a phantom were simulated. Following the phantom simulation, a dummy patient CT dataset was used to simulate a boron neutron capture therapy (BNCT) irradiation of the brain. A mock tumor located at 4, 6, 8 cm along the central axis and 4‐cm off‐axis was set, and the dose distribution was simulated for a maximum total biologically weighted brain dose of 12.5 Gy with a beam entering from the vertex.

Results

All three filters improved the beam penetration of the accelerator‐based neutron source. Filter design C was found to be the most suitable filter, increasing the advantage depth from 9.1 to 9.9 cm. Compared with the unfiltered beam, the mean weighted dose in the tumor located at a depth of 8 cm along the beam axis was increased by ∼25%, and 34% for the tumor located at a depth of 8 cm and off‐axis by 4 cm.

Conclusion

A neutron filtration system for an accelerator‐based BNCT system was investigated using Monte Carlo simulation. The proposed filter design significantly improved the dose distribution for the treatment of deep targets in the brain.
Assessment of dose‐volume histogram precision for five clinical systems
Authors: Pepin Mark D. , Penoncello Gregory P. , Brom Kevin M. , Gustafson Jon M. , Long Kenneth M. , Rong Yi , Fong de los Santos Luis E. , Shiraishi Satomi
Published: August 2022

Purpose

To investigate the dependency of dose‐volume histogram (DVH) behavior and precision on underlying discretization using shapes and dose distributions with known analytical DVHs for five commercial DVH calculators.

Methods

DVHs and summary metrics were extracted from all five systems using synthetic cone and cylinder objects for which the true volume and DVH curves were known. Trends in the curves and metrics were explored by varying the underlying voxelization of the CT image, structure set, and dose grid as well by varying the geometry of the structure and direction of a linear dose gradient. Using synthetic structures allowed for comparison with ground truth DVH curves to assess their accuracy while an algorithm was additionally developed to assess the precision of each system. The precision was calculated with a novel algorithm that treats any “stair step” behavior in a DVH curve as an uncertainty band and calculates the width, characterized as a percent difference, of the band for various DVH metrics. The underlying voxelization was additionally changed and DVHs were extracted for two clinical examples. The details of how each system calculated DVHs were also investigated and tendencies in the calculated curves, metrics, and precision were related to choices made in the calculation methodology.

Results

Calculation methodology differences that had a noticeable impact on the DVH curves and summary metrics include supersampling beyond the input grids and interpretation of the superior and inferior ends of the structures. Among the systems studied, the median precision ranged from 0.902% to 3.22%, and interquartile ranges varied from 1.09% to 3.91%.

Conclusions

Commercial dose‐evaluation solutions can calculate different DVH curves, structure volume measures, and dose statistics for the same input data due to differences in their calculation methodologies. This study highlights the importance of understanding and investigating the DVH calculation when considering a new clinical system and when using more than one system for data transfer.
Dual‐domain reconstruction network with V‐Net and K‐Net for fast MRI
Authors: Liu Xiaohan , Pang Yanwei , Jin Ruiqi , Liu Yu , Wang Zhenchang
Published: August 2022

Purpose

To introduce a dual‐domain reconstruction network with V‐Net and K‐Net for accurate MR image reconstruction from undersampled k‐space data.

Methods

Most state‐of‐the‐art reconstruction methods apply U‐Net or cascaded U‐Nets in the image domain and/or k‐space domain. Nevertheless, these methods have the following problems: (1) directly applying U‐Net in the k‐space domain is not optimal for extracting features; (2) classical image‐domain–oriented U‐Net is heavyweighted and hence inefficient when cascaded many times to yield good reconstruction accuracy; (3) classical image‐domain–oriented U‐Net does not make full use of information of the encoder network for extracting features in the decoder network; and (4) existing methods are ineffective in simultaneously extracting and fusing features in the image domain and its dual k‐space domain. To tackle these problems, we present 3 different methods: (1) V‐Net, an image‐domain encoder–decoder subnetwork that is more lightweight for cascading and effective in fully utilizing features in the encoder for decoding; (2) K‐Net, a k‐space domain subnetwork that is more suitable for extracting hierarchical features in the k‐space domain, and (3) KV‐Net, a dual‐domain reconstruction network in which V‐Nets and K‐Nets are effectively combined and cascaded.

Results

Extensive experimental results on the fastMRI dataset demonstrate that the proposed KV‐Net can reconstruct high‐quality images and outperform state‐of‐the‐art approaches with fewer parameters.

Conclusions

To reconstruct images effectively and efficiently from incomplete k‐space data, we have presented a dual‐domain KV‐Net to combine K‐Nets and V‐Nets. The KV‐Net achieves better results with 9% and 5% parameters than comparable methods (XPD‐Net and i‐RIM).