bluuebunny/crossref_metadata_2025 huggingface dataset:
α1-Adrenergic receptor–PKC–Pyk2–Src signaling boosts L-type Ca2+ channel CaV1.2 activity and long-term potentiation in rodents
Authors: Man Kwun Nok Mimi , Bartels Peter , Henderson Peter B , Kim Karam , Shi Mei , Zhang Mingxu , Ho Sheng-Yang , Nieves-Cintron Madeline , Navedo Manuel F , Horne Mary C , Hell Johannes W
Published: June 2023

The cellular mechanisms mediating norepinephrine (NE) functions in brain to result in behaviors are unknown. We identified the L-type Ca2+ channel (LTCC) CaV1.2 as a principal target for Gq-coupled α1-adrenergic receptors (ARs). α1AR signaling increased LTCC activity in hippocampal neurons. This regulation required protein kinase C (PKC)-mediated activation of the tyrosine kinases Pyk2 and, downstream, Src. Pyk2 and Src were associated with CaV1.2. In model neuroendocrine PC12 cells, stimulation of PKC induced tyrosine phosphorylation of CaV1.2, a modification abrogated by inhibition of Pyk2 and Src. Upregulation of LTCC activity by α1AR and formation of a signaling complex with PKC, Pyk2, and Src suggests that CaV1.2 is a central conduit for signaling by NE. Indeed, a form of hippocampal long-term potentiation (LTP) in young mice requires both the LTCC and α1AR stimulation. Inhibition of Pyk2 and Src blocked this LTP, indicating that enhancement of CaV1.2 activity via α1AR–Pyk2–Src signaling regulates synaptic strength.
Constitutive activation and oncogenicity are mediated by loss of helical structure at the cytosolic boundary of thrombopoietin receptor mutant dimers
Authors: Defour Jean-Philippe , Leroy Emilie , Dass Sharmila , Balligand Thomas , Levy Gabriel , Brett Ian C , Papadopoulos Nicolas , Mouton Céline , Genet Lidvine , Pecquet Christian , Staerk Judith , Smith Steven O , Constantinescu Stefan N
Published: June 2023

Dimerization of the thrombopoietin receptor (TpoR) is necessary for receptor activation and downstream signaling through activated Janus kinase 2. We have shown previously that different orientations of the transmembrane (TM) helices within a receptor dimer can lead to different signaling outputs. Here we addressed the structural basis of activation for receptor mutations S505N and W515K that induce myeloproliferative neoplasms. We show using in vivo bone marrow reconstitution experiments that ligand-independent activation of TpoR by TM asparagine (Asn) substitutions is proportional to the proximity of the Asn mutation to the intracellular membrane surface. Solid-state NMR experiments on TM peptides indicate a progressive loss of helical structure in the juxtamembrane (JM) R/KWQFP motif with proximity of Asn substitutions to the cytosolic boundary. Mutational studies in the TpoR cytosolic JM region show that loss of the helical structure in the JM motif by itself can induce activation, but only when localized to a maximum of six amino acids downstream of W515, the helicity of the remaining region until Box 1 being required for receptor function. The constitutive activation of TpoR mutants S505N and W515K can be inhibited by rotation of TM helices within the TpoR dimer, which also restores helicity around W515. Together, these data allow us to develop a general model for activation of TpoR and explain the critical role of the JM W515 residue in the regulation of the activity of the receptor.
Why did glutamate, GABA, and melatonin become intercellular signalling molecules in plants?
Authors: Caspi Yaron , Pantazopoulou Chrysoula K , Prompers Jeanine J , Pieterse Corné MJ , Hulshoff Pol Hilleke , Kajala Kaisa
Published: June 2023

Intercellular signalling is an indispensable part of multicellular life. Understanding the commonalities and differences in how signalling molecules function in two remote branches of the tree of life may shed light on the reasons these molecules were originally recruited for intercellular signalling. Here we review the plant function of three highly studied animal intercellular signalling molecules, namely glutamate, γ-aminobutyric acid (GABA), and melatonin. By considering both their signalling function in plants and their broader physiological function, we suggest that molecules with an original function as key metabolites or active participants in reactive ion species scavenging have a high chance of becoming intercellular signalling molecules. Naturally, the evolution of machinery to transduce a message across the plasma membrane is necessary. This fact is demonstrated by three other well-studied animal intercellular signalling molecules, namely serotonin, dopamine, and acetylcholine, for which there is currently no evidence that they act as intercellular signalling molecules in plants.
FUS regulates RAN translation through modulating the G-quadruplex structure of GGGGCC repeat RNA in C9orf72-linked ALS/FTD
Authors: Fujino Yuzo , Ueyama Morio , Ishiguro Taro , Ozawa Daisaku , Ito Hayato , Sugiki Toshihiko , Murata Asako , Ishiguro Akira , Gendron Tania F. , Mori Kohji , Tokuda Eiichi , Taminato Tomoya , Konno Takuya , Koyama Akihide , Kawabe Yuya , Takeuchi Toshihide , Furukawa Yoshiaki , Fujiwara Toshimichi , Ikeda Manabu , Mizuno Toshiki , Mochizuki Hideki , Mizusawa Hidehiro , Wada Keiji , Ishikawa Kinya , Onodera Osamu , Nakatani Kazuhiko , Petrucelli Leonard , Taguchi Hideki , Nagai Yoshitaka
Published: June 2023

Abnormal expansions of GGGGCC repeat sequence in the noncoding region of the
C9orf72
gene is the most common cause of familial amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD). The expanded repeat sequence is translated into dipeptide repeat proteins (DPRs) by noncanonical repeat-associated non-AUG (RAN) translation. Since DPRs play central roles in the pathogenesis of C9-ALS/FTD, we here investigate the regulatory mechanisms of RAN translation, focusing on the effects of RNA-binding proteins (RBPs) targeting GGGGCC repeat RNAs. Using C9-ALS/FTD model flies, we demonstrated that the ALS/FTD-linked RBP FUS suppresses RAN translation and neurodegeneration in an RNA-binding activity-dependent manner. Moreover, we found that FUS directly binds to and modulates the G-quadruplex structure of GGGGCC repeat RNA as an RNA chaperone, resulting in the suppression of RAN translation
in vitro
. These results reveal a previously unrecognized regulatory mechanism of RAN translation by G-quadruplex-targeting RBPs, providing therapeutic insights for C9-ALS/FTD and other repeat expansion diseases.
Diameter Dependence of Transport through Nuclear Pore Complex Mimics Studied Using Optical Nanopores
Authors: Klughammer Nils , Barth Anders , Dekker Maurice , Fragasso Alessio , Onck Patrick R. , Dekker Cees
Published: June 2023

The nuclear pore complex (NPC) regulates the selective transport of large biomolecules through the nuclear envelope. As a model system for nuclear transport, we construct NPC mimics by functionalizing the pore walls of freestanding palladium zero-mode waveguides with the FG-nucleoporin Nsp1. This approach enables the measurement of single-molecule translocations through individual pores using optical detection. We probe the selectivity of Nsp1-coated pores by quantitatively comparing the translocation rates of the nuclear transport receptor Kap95 to the inert probe BSA over a wide range of pore sizes from 35 nm to 160 nm. Pores below 55 ± 5 nm show significant selectivity that gradually decreases for larger pores. This finding is corroborated by coarse-grained molecular-dynamics simulations of the Nsp1 mesh within the pore, which suggest that leakage of BSA occurs by diffusion through transient openings within the dynamic mesh. Furthermore, we experimentally observe a modulation of the BSA permeation when varying the concentration of Kap95. The results demonstrate the potential of single-molecule fluorescence measurements on biomimetic NPCs to elucidate the principles of nuclear transport.
Chromosome-level genome assembly of hadal snailfish reveals mechanisms of deep-sea adaptation in vertebrates
Authors: Xu Wenjie , Zhu Chenglong , Gao Xueli , Wu Baosheng , Xu Han , Hu Mingliang , Zeng Honghui , Gan Xiaoni , Feng Chenguang , Zheng Jiangmin , Bo Jing , He Li-Sheng , Qiu Qiang , Wang Wen , He Shunping , Wang Kun
Published: June 2023

As the deepest vertebrate in the ocean, the hadal snailfish (Pseudoliparis swirei), which lives at a depth of 6,000–8,000 m, is a representative case for studying adaptation to extreme environments. Despite some preliminary studies on this species in recent years, including their loss of pigmentation, visual and skeletal calcification genes, and the role of trimethylamine N-oxide in adaptation to high-hydrostatic pressure, it is still unknown how they evolved and why they are among the few vertebrate species that have successfully adapted to the deep-sea environment. Using genomic data from different trenches, we found that the hadal snailfish may have entered and fully adapted to such extreme environments only in the last few million years. Meanwhile, phylogenetic relationships show that they spread into different trenches in the Pacific Ocean within a million years. Comparative genomic analysis has also revealed that the genes associated with perception, circadian rhythms, and metabolism have been extensively modified in the hadal snailfish to adapt to its unique environment. More importantly, the tandem duplication of a gene encoding ferritin significantly increased their tolerance to reactive oxygen species, which may be one of the important factors in their adaptation to high-hydrostatic pressure.
Chromosome-level genome assembly of hadal snailfish reveals mechanisms of deep-sea adaptation in vertebrates
Authors: Xu Wen-Jie , Zhu Chenglong , Gao Xueli , Wu Baosheng , Xu Han , Hu Ming-Liang , Zeng Honghui , Gan Xiaoni , Feng Chen-Guang , Zheng Jiangmin , Bo Jing , He Lisheng , Qiu Qiang , Wang Wen , He Shunping , Wang Kun
Published: June 2023

As the deepest vertebrate in the ocean, the hadal snailfish (
Pseudoliparis swirei
), which lives at a depth of 6,000~8,000m, is a representative case for studying adaptation to extreme environments. Despite some preliminary studies on this species in recent years, including their loss of pigmentation, visual and skeletal calcification genes, and the role of TMAO in adaptation to high-hydrostatic pressure, it is still unknown how they evolved and why they are among the few vertebrate species that have successfully adapted to the deep sea environment. Using genomic data from different trenches, we found that the hadal snailfish may have entered and fully adapted to such extreme environments only in the last few million years. Meanwhile, phylogenetic relationships show that they spread into different trenches in the Pacific Ocean within a million years. Comparative genomic analysis has also revealed that the genes associated with perception, circadian rhythms, and metabolism have been extensively modified in the hadal snailfish to adapt to its unique environment. More importantly, the tandem duplication of a gene encoding ferritin significantly increased their tolerance to reactive oxygen species, which may be one of the important factors in their adaptation to high-hydrostatic pressure.
Hepatic conversion of acetyl-CoA to acetate plays crucial roles in energy stresses
Authors: Wang Jinyang , Wen Yaxin , Zhao Wentao , Zhang Yan , Lin Furong , Ouyang Cong , Wang Huihui , Yao Lizheng , Ma Huanhuan , Zhuo Yue , Huang Huiying , Shi Xiulin , Feng Liubin , Lin Donghai , Jiang Bin , Li Qinxi
Published: June 2023

Accumulating evidences indicate that acetate is increased in energy stresses such as diabetes mellitus and prolonged starvation. However, it is largely unknown how and where acetate is produced and what is its biological significance. We observed overproduction of acetate in an amount comparable to ketone bodies in patients and mice with diabetes or starvation. Mechanistically, ACOT 12&8 are dramatically upregulated in liver to convert FFA-derived acetyl-CoA to acetate and CoA. This conversion not only provides large amount of acetate which fuels brain preferentially rather than muscle, but also recycles CoA which is required for sustained fatty acid oxidation and ketogenesis. Taken together, we suggest that acetate is an emerging novel ketone body and may be used as a parameter to evaluate the progression of energy stress in the future.
Vaccination with mycobacterial lipid loaded nanoparticle leads to lipid antigen persistence and memory differentiation of antigen-specific T cells
Authors: Morgun Eva , Zhu Jennifer , Almunif Sultan , Bobbala Sharan , Aguilar Melissa S. , Wang Junzhong , Conner Kathleen , Cui Yongyong , Cao Liang , Seshadri Chetan , Scott Evan A. , Wang Chyung-Ru
Published: June 2023

Mycobacterium tuberculosis
(Mtb) infection elicits both protein and lipid antigen-specific T cell responses. However, the incorporation of lipid antigens into subunit vaccine strategies and formulations has been under-explored, and the properties of vaccine-induced Mtb lipid-specific memory T cells have remained elusive. Mycolic acid (MA), a major lipid component of the Mtb cell wall, is presented by human CD1b molecules to unconventional T cell subsets. These MA-specific CD1b-restricted T cells have been detected in the blood and disease sites of Mtb-infected individuals, suggesting that MA is a promising lipid antigen for incorporation into multicomponent subunit vaccines. In this study, we utilized the enhanced stability of bicontinuous nanospheres (BCN) to efficiently encapsulate MA for delivery
in vivo
to MA-specific T cells both alone and in combination with an immunodominant Mtb protein antigen (Ag85B). Pulmonary delivery of MA-loaded BCN (MA-BCN) elicited MA-specific T cell responses in humanized CD1 transgenic mice. Simultaneous delivery of MA and Ag85B within BCN activated both MA- and Ag85B-specific T cells. Interestingly, pulmonary vaccination with MA-Ag85B-BCN led to the persistence of MA, but not Ag85B, within alveolar macrophages in the lung. Vaccination of MA-BCN through intravenous or subcutaneous route, or with attenuated Mtb likewise reproduced MA persistence. Moreover, MA-specific T cells in MA-BCN-vaccinated mice differentiated into a T follicular helper-like phenotype. Overall, the BCN platform allows for the dual encapsulation and
in vivo
activation of lipid and protein antigen-specific T cells and leads to persistent lipid depots that could offer long-lasting immune responses.
Influence of coarse aggregate granulometry on clogging in pervious concrete
Authors: Barreto Sandoval G. F. , Mota L. J. A. , Pieralisi R. , De Souza Risson K. D. B.
Published: June 2023

The phenomenon of clogging in pervious concrete (PC) has been one of the main causes of the hydraulic useful life reduction. This phenomenon begins with the partial or total clogging of the pore network and consequently the reduction of the permeability coefficient. Considering that the porous network of the PC is directly related to the aggregate used, the present work aims to evaluate the influence of granulometry on the clogging of the PC. The results showed that the largest aggregate size (D_max=19 mm) favors the hydraulic properties of the material. However, the variation of the granulometry grading distribution (poorly graded and single-sized) does not generate a significant difference in such results. In terms of clogging, there was a marked effect on the type of the granulometry grading distribution, the use of poorly graded aggregates led to a lower permeability reduction due to clogging when compared to PCs with single-sized aggregates.
The Impact of the Companys Characteristics on Earnings Management Based on Accrual: A Case of the United Arab Emirates
Authors: Hadi Ali Majed , Al-hamood Dr. Mundher , Ali Dr. Hashim
Published: June 2023

The aim of this research is to explore the impact of the companys characteristics in earnings management. In more detail, explore the impact of the companys size, leverage, growth, turnover of assets and loss on accruals earnings management. In order to test the studys hypothesis, researchers used financial data of companies listed in the UAE markets (Abu Dhabi Financial Market and Dubai Financial Market). The researchers concluded that the companys characteristics do not affect accruals earnings management with the exception of turnover and loss. This result suggests that earnings management is only a decision taken by management and is therefore more related to management as people than the companys characteristics. This result also indicates that companies facing a loss tend to manage their earnings more than companies whose activity results positively.
APRENDIZAJE INTERCULTURAL Y ENSEÑANZA DE LA DIVERSIDAD LINGÜÍSTICA DEL ESPAÑOL EN EL CONTEXTO BRASILEÑO
Authors: Venâncio da Silva Bruno Rafael Costa
Published: June 2023

En el contexto brasileño de enseñanza, la diversidad lingüístico-cultural del español suele tratarse de manera superficial y anecdótica, además de la presencia casi exclusiva de determinados países o regiones hispanohablantes, frente a otros que son invisibilizados en el aula. La formación de profesores sigue sin ofrecer el soporte teórico-metodológico por medio de componentes curriculares que reflexionen sobre la variación lingüística de esa lengua y su aplicación didáctica. Así, este artículo tiene como objetivo discutir los beneficios de una educación intercultural, en la que la diversidad lingüístico-cultural se contemple en las clases de español. Para ello, discutimos el tratamiento del componente cultural y del aprendizaje intercultural (BYRAM, 1989; SERRANI, 2005; KRAMSCH, 2017; PAIVA; VIANA, 2017) aplicado a la diversidad lingüística. También discutimos algunas dificultades, prejuicios e impedimentos para tratar la diversidad lingüístico-cultural del español en Brasil a partir de los estudios de Irala (2004), Moreno Fernández (2010), Zolin-Vesz (2013), Venâncio da Silva y Andión (2019), Venâncio da Silva (2020). Finalmente, hemos elaborado una propuesta intercultural para aprovechar al máximo la variación lingüística a través de textos en ambas lenguas que contribuyan a desarrollar actitudes tolerantes hacia ese fenómeno y que los estudiantes conozcan variantes gramaticales que están presentes en el portugués brasileño y en variedades hispanoamericanas del español.
Screening for Anxiety Disorders in Adults
Authors: Jin Jill
Published: June 2023

This JAMA Patient Page describes the pros and cons of screening for anxiety disorders in adults.
Time series analysis showing how different environmental conditions affect the interspecific interactions of Callosobruchus maculatus and Callosobruchus chinensis
Authors: Kawase Takanori , Kyogoku Daisuke , Kawatsu Kazutaka , Katayama Noboru , Miki Takeshi , Kondoh Michio
Published: June 2023

Environmental changes alter the strength of interspecific interactions. However, because it is difficult to quantify interaction strength, empirical evidence remains limited on the relationships among environmental change, interaction strength, and consequences on population dynamics. Here, we evaluated how the interactions of two species of Callosobruchus seed beetles changed with increasing the cage size of the experiments and then affected the coexistence period as a property of population dynamics. Specifically, competition experiments were conducted on Callosobruchus maculatus (C. maculatus) and Callosobruchus chinensis (C. chinensis) using cages of different sizes, which altered the density of adults. We focused on two modes of interspecific interactions between these two species: larval resource competition and adult reproductive interference. Convergent cross mapping (CCM) was implemented to the experimental time series of the two species to assess how environmental change altered their interaction strength and the coexistence period (as a proxy of population dynamics). In most replications, C. maculatus persisted, whereas C. chinensis became extinct. The coexistence periods were longer with increasing cage size. However, there was no statistically significant relationship between cage size and interaction strength. Nevertheless, the stronger (or weaker) interaction strength of the competitively inferior (superior) species on competitively superior (inferior) was associated with longer coexistence periods. Overall, this study demonstrated that interaction strength affected population dynamics; however, changing interaction strength by altering environmental conditions did not necessarily mean that increasing habitat size reduces competition strength.
Cryo‐EM structures of tau filaments from SH‐SY5Y cells seeded with brain extracts from cases of Alzheimer's disease and corticobasal degeneration
Authors: Tarutani Airi , Lövestam Sofia , Zhang Xianjun , Kotecha Abhay , Robinson Andrew C. , Mann David M. A. , Saito Yuko , Murayama Shigeo , Tomita Taisuke , Goedert Michel , Scheres Sjors H. W. , Hasegawa Masato
Published: June 2023

The formation of amyloid filaments through templated seeding is believed to underlie the propagation of pathology in most human neurodegenerative diseases. A widely used model system to study this process is to seed amyloid filament formation in cultured cells using human brain extracts. Here, we report the electron cryo‐microscopy structures of tau filaments from  undifferentiated seeded SH‐SY5Y cells that transiently expressed N‐terminally HA‐tagged 1N3R or 1N4R human tau, using brain extracts from individuals with Alzheimer's disease or corticobasal degeneration. Although the resulting filament structures differed from those of the brain seeds, some degrees of structural templating were observed. Studying templated seeding in cultured cells, and determining the structures of the resulting filaments, can thus provide insights into the cellular aspects underlying neurodegenerative diseases.
Bifunctional Electrode Design Targeting Co‐Enhanced Kinetics and Mass Transport for Hydrogen and Water Oxidation Reactions
Authors: Kim Ye Ji , Lim Ahyoun , Lee Gyu Rac , Kim Minjoon , Kim Jin Young , Kim Jong Min , Jung Yeon Sik , Park Hyun S.
Published: June 2023

Bifunctional catalysts based on noble metals have achieved practical‐level performances in round‐trip energy conversion systems. However, the required amount of noble metals should be substantially reduced via a new catalyst design that can pursue the synergy of the constituent materials’ intrinsic properties and architectural maneuver over reactant/product transport. In this study, cross‐stacked Ir and Pt nanowires resolved the bottlenecks of two reactions essential for the hydrogen‐based energy system: i) hydrogen spillover phenomenon between Pt and Ir nanowires to expedite the hydrogen oxidation reaction and ii) spacing Ir nanowires sufficiently to enhance the mass transport of the oxygen evolution reaction. Simultaneously accommodating the different strategies within the single catalyst layer, a new horizon to design a bifunctional electrode is proposed with the high performance of polymer electrolyte membrane unitized regenerative fuel cells: 47% of round‐trip efficiency at 0.5 A cm−2 with total noble metal loading < 0.3 mg cm−2.
Nafion Matrix and Ionic Domain Tuning for High‐Performance Composite Proton Exchange Membranes
Authors: Smith Keenan , Foglia Fabrizia , Clancy Adam J. , Brett Dan J. L. , Miller Thomas S.
Published: June 2023

Although proton exchange membranes (PEMs) are widely deployed in an array of commercial applications, limitations linked to their proton conductivity, water retention, and gas permeability still limit ultimate device performance. While ex situ studies have shown additives can enhance membrane stability and mass transport, to date few have demonstrated that these performance enhancements are maintained when tested in commercially relevant electrochemical technologies, such as fuel cells or electrolyzers. Herein, a new multifunctional additive, 2D poly(triazine imide) (PTI), is demonstrated for composite PEMs, which is shown to boost proton conductivity by 37% under optimal high relative humidity (RH) conditions and 67% at low RHs. PTI also enables major improvements (over 55%) in both current and power densities in industrially relevant PEM fuel cells (PEMFCs). Most importantly, in situ and ex situ characterization suggests that the enhanced performance is due to polymer aggregate‐PTI clusters that form with increasing 2D character and improved long‐range connectivity, while acid‐base interactions with pyridinic nitrogen facilitate the critical proton hopping mechanism at all RHs. Hence, this work offers both a new membrane concept with proven benefits for important electrochemical technologies, as well as design principles for future optimization of proton transport and water management within PEMs.
Coaxial Nanowire Electrodes Enable Exceptional Fuel Cell Durability
Authors: Yang Gaoqiang , Komini Babu Siddharth , Liyanage Wipula P. R. , Martinez Ulises , Routkevitch Dmitri , Mukundan Rangachary , Borup Rodney L. , Cullen David A. , Spendelow Jacob S.
Published: June 2023

Polymer‐electrolyte‐membrane fuel cells (PEMFCs) hold great promise for applications in clean energy conversion, but cost and durability continue to limit commercialization. This work presents a new class of catalyst/electrode architecture that does not rely on Pt particles or carbon supports, eliminating the primary degradation mechanisms in conventional electrodes, and thereby enabling transformative durability improvements. The coaxial nanowire electrode (CANE) architecture consists of an array of vertically aligned nanowires, each comprising an ionomer core encapsulated by a nanoscale Pt film. This unique design eliminates the triple‐phase boundary and replaces it with two double‐phase boundaries, increasing Pt utilization. It also eliminates the need for carbon support and ionomer binder, enabling improved durability and faster mass transport. Fuel cell membrane electrode assemblies based on CANEs demonstrate extraordinary durability in accelerated stress tests (ASTs), with only 2% and 5% loss in performance after 5000 support AST cycles and 30000 catalysts AST cycles, respectively. The high power density and extremely high durability provided by CANEs can enable a paradigm shift from random electrodes based on unstable platinum nanoparticles dispersed on carbon to ordered electrodes based on durable Pt nanofilms, facilitating rapid deployment of fuel cells in transportation and other clean energy applications.
Flexible, Transparent, and Wafer‐Scale Artificial Synapse Array Based on TiOx/Ti3C2Tx Film for Neuromorphic Computing
Authors: Huang Junhua , Yang Shaodian , Tang Xin , Yang Leilei , Chen Wenjun , Chen Zibo , Li Xinming , Zeng Zhiping , Tang Zikang , Gui Xuchun
Published: June 2023

A high‐density neuromorphic computing memristor array based on 2D materials paves the way for next‐generation information‐processing components and in‐memory computing systems. However, the traditional 2D‐materials‐based memristor devices suffer from poor flexibility and opacity, which hinders the application of memristors in flexible electronics. Here, a flexible artificial synapse array based on TiOx/Ti3C2Tx film is fabricated by a convenient and energy‐efficient solution‐processing technique, which realizes high transmittance (≈90%) and oxidation resistance (>30 days). The TiOx/Ti3C2Tx memristor shows low device‐to‐device variability, long memory retention and endurance, a high ON/OFF ratio, and fundamental synaptic behavior. Furthermore, satisfactory flexibility (R = 1.0 mm) and mechanical endurance (104 bending cycles) of the TiOx/Ti3C2Tx memristor are achieved, which is superior to other film memristors prepared by chemical vapor deposition. In addition, high‐precision (>96.44%) MNIST handwritten digits recognition classification simulation indicates that the TiOx/Ti3C2Tx artificial synapse array holds promise for future neuromorphic computing applications, and provides excellent high‐density neuron circuits for new flexible intelligent electronic equipment.
Highly Selective Conversion of CH4 to High Value‐Added C1 Oxygenates over Pd Loaded ZnTi‐LDH
Authors: Fu Lei , Zhang Ruixue , Yang Jianlong , Shi Jiale , Jiang Hai‐Ying , Tang Junwang
Published: June 2023

The selective oxidation of methane to high value‐added liquid oxygenated compounds under mild conditions is of great significance to promote the efficient utilization of the carbon source, but it also faces the dilemma of low activity and over‐oxidation. Here, ZnTi‐layered double hydroxides (LDH)‐A200 photocatalysts with Pd loading are prepared to achieve efficient oxidation of methane, with O2 as an oxidant under ambient condition. The highest generation rate of C1 liquid products (methanol and formaldehyde) reaches 4924.47 µmol g−1 h−1 with a selectivity close to 100% over 0.5Pd‐ZnTi‐LDH‐A200, which is 20 times higher than that of bare ZnTi‐LDH‐A200. The photochemical results show that the modified photocatalysts present much higher generation and separation efficiency of electron‐hole pairs. In situ X–ray photoelectron spectroscopy indicates that Pd nanoparticles are the hole acceptor, which is beneficial to charge separation in the photocatalysis. Furthermore, electron spinresonance spectroscopy and temperature–programmed–desorption analysis prove that Pd loading is helpful to the adsorption of methane and oxygen on the surface of ZnTi‐LDH‐A200, promoting the production of reactive oxygen species and activation of methane. All these factors work together to promote the efficient conversion of CH4 to high value‐added C1 oxygenates.
Machine learning for major food crops breeding: Applications, challenges, and ways forward
Authors: N. Govaichelvan Kumanan , Pathmanathan Dharini , Zainal‐Abidin Rabiatul‐Adawiah , Abu Arpah
Published: June 2023

Increasing the production of the three major food crops (MFCs), maize (Zea mays), rice (Oryza sativa), and wheat (Triticum aestivum), is essential to fulfilling the food demand for the growing human population. Increasing food production may require the integration of machine learning (ML) into plant breeding programs. However, developing ML tools to improve the production of MFCs is a daunting task due to the lack of quality data and the computation resources needed to process this information. Hence, this review discusses the recent applications of ML for improving MFCs production, including plant phenotyping, yield forecasting, and candidate gene prediction. Based on the challenges reported in recent ML experiments for MFCs, this review prescribes solutions to produce scalable ML models. This review provides valuable insights for future studies and promotes collective efforts among researchers implementing ML to enhance MFCs productivity.
Healthcare experiences of patients with Down syndrome from primarily Spanish‐speaking households
Authors: Chung Jeanhee , Krell Kavita , Pless Albert , Michael Carie , Torres Amy , Baker Sandra , Blake Jasmine M. , Caughman Kelli , Cullen Sarah , Gallagher Maureen , Hoke‐Chandler Roxanne , Maina Julius , McLuckie Diana , O'Neill Kate , Peña Angeles , Royal Dina , Slape Michelle , Spinazzi Noemi Alice , Torres Carlos G. , Skotko Brian G.
Published: June 2023

We report on the health care experiences of individuals with Down syndrome (DS) from families who are primarily Spanish‐speaking. Data were collected through three methods: (1) a nationally distributed, 20‐item survey, (2) two focus groups with seven family caregivers of individuals with DS who self‐identified as living in primarily Spanish speaking households, and (3) 20 interviews with primary care providers (PCPs) who care for patients who are underrepresented minorities. Standard summary statistics were used to analyze the quantitative survey results. Focus group and interview transcripts, as well as an open‐ended response question in the survey, were analyzed using qualitative coding methods to identify key themes. Both caregivers and PCPs described how language barriers make giving and receiving quality care difficult. Caregivers additionally described condescending, discriminatory treatment within the medical system and shared feelings of caregiver stress and social isolation. Challenges to care experienced by families of individuals with DS are compounded for Spanish‐speaking families, where the ability to build trust with providers and in the health care system may be compromised by cultural and language differences, systemic issues (lack of time or inability to craft more nuanced schedules so that patients with higher needs are offered more time), mistrust, and sometimes, overt racism. Building this trust is critical to improve access to information, care options, and research opportunities, especially for this community that depends on their clinicians and nonprofit groups as trusted messengers. More study is needed to understand how to better reach out to these communities through primary care clinician networks and nonprofit organizations.
Mesoporous Metal–Organic Frameworks for Catalytic RNA Deprotection and Activation
Authors: Liu Jin , Liu Xingyu , Liu Qi , Cao Jing , Lv Xinheng , Wang Shaoru , Tian Tian , Zhou Xiang , Deng Hexiang
Published: June 2023

A metal–organic framework (MOF) with mespores (2 to 50 nm) allows the inclusion of large biomolecules, such as nucleic acids. However, chemical reaction on the nucleic acids, to further regulate their bioactivity, is yet to be demonstrated within MOF pores. Here, we report the deprotection of carbonate protected RNA molecules (21 to 102 nt) to restore their original activity using a MOF as a heterogeneous catalyst. Two MOFs, MOF‐626 and MOF‐636 are designed and synthesized, with mesopores of 2.2 and 2.8 nm, respectively, carrying isolated metal sites (Ni, Co, Cu, Pd, Rh and Ru). The pores favor the entrance of RNA, while the metal sites catalyze C−O bond cleavage at the carbonate group. Complete conversion of RNA is achieved by Pd‐MOF‐626, 90 times more efficiently than Pd(NO3)2. MOF crystals are also removable from the aqueous reaction media, leaving a negligible metal footprint, 3.9 ppb, only 1/55 of that using homogeneous Pd catalysts. These features make MOF potentially suited for bioorthogonal chemistry.
Synergistic intrafibrillar/extrafibrillar mineralization of collagen fibrils and scaffolds enhanced by introducing polyacrylamide to PILP for osteogenic differentiation
Authors: Liu Chengde , Jiang Luyao , Du Wanting , Cheng Xitong , Zhao Zheng , Wang Jinyan , Jian Xigao
Published: June 2023

Mineralization can help improve the mechanical properties and degradation rates of collagen scaffolds while ensuring good biocompatibility, thereby providing a suitable microenvironment for osteogenic differentiation. Intrafibrillar/extrafibrillar mineralization of collagen is promoted by polymer‐induced liquid precursors (PILP). In this study, polyacrylamide (PAM) was introduced to PILP which synergistically mineralized collagen scaffold intrafibrillarly and extrafibrillarly. PAM and polyacrylic acid (PAA) can stabilize the amorphous calcium phosphate (ACP), to form a PILP of PAM and PAA/ACP. As a control, another scaffold material was formed using the conventional mineralization method, that is, soaking collagen in a simulated body fluid. Collagen mineralization was characterized using SEM and TEM. After 7 days of mineralization with PILP, intrafibrillar crystallization of collagen was significantly higher than that in the control group, and the stiffness and modulus of this scaffold material significantly increased. Cellular experiment results indicated that the PILP‐mineralized collagen scaffold was biocompatible and promoted the osteogenic differentiation of MC3T3‐E1 pre‐osteoblasts. Biomimetic mineralization by PILP will assist the fabrication of mineralized collagen scaffold for bone repair applications.
Causal decomposition maps: An exploratory tool for designing area‐level interventions aimed at reducing health disparities
Authors: Smith Melissa J. , Charlton Mary E. , Oleson Jacob J.
Published: June 2023

Methods for decomposition analyses have been developed to partition between‐group differences into explained and unexplained portions. In this paper, we introduce the concept of causal decomposition maps, which allow researchers to test the effect of area‐level interventions on disease maps before implementation. These maps quantify the impact of interventions that aim to reduce differences in health outcomes between groups and illustrate how the disease map might change under different interventions. We adapt a new causal decomposition analysis method for the disease mapping context. Through the specification of a Bayesian hierarchical outcome model, we obtain counterfactual small area estimates of age‐adjusted rates and reliable estimates of decomposition quantities. We present two formulations of the outcome model, with the second allowing for spatial interference of the intervention. Our method is utilized to determine whether the addition of gyms in different sets of rural ZIP codes could reduce any of the rural–urban difference in age‐adjusted colorectal cancer incidence rates in Iowa ZIP codes.
Nomograms for postsurgical extrahepatic recurrence prediction of hepatocellular carcinoma based on presurgical circulating tumor cell status and clinicopathological factors
Authors: Wei Hao‐Wen , Qin Shui‐Ling , Xu Jing‐Xuan , Huang Yi‐Yue , Chen Yuan‐Yuan , Ma Liang , Qi Lu‐Nan
Published: June 2023

Background and Aims

Extrahepatic recurrence (EHR) is one of the major reasons for the poor prognosis of hepatocellular carcinoma (HCC). The present study aimed to develop and assess the performance of predictive models by using a combination of presurgical circulating tumor cell (CTCs) data and clinicopathological features to screen patients at high risk of EHR to achieve precise decision‐making.

Patients and Methods

A total of 227 patients with recurrent HCC and preoperative CTC data from January 2014 to August 2019 were enrolled. All patients were randomly assigned to one of two cohorts: development or validation. Two preoperative and postoperative nomogram models for EHR prediction were developed and multi‐dimensionally validated.

Results

Patients with EHR had generally lower recurrence‐free survival (p < 0.001), and overall survival (p < 0.001), and significantly higher CTC counts (epithelial CTCs, epithelial/mesenchymal hybrid CTCs, and mesenchymal CTCs count, all p < 0.05) than those without EHR. Univariate and multivariate analyses revealed that EHR was associated with four risk factors in the development cohort: total CTC count (p = 0.014), tumor size (p = 0.028), node number (p = 0.045), and microvascular invasion (p = 0.035). These factors were incorporated into two nomogram models (preoperative and postoperative), which reliably predicted EHR through multidimensional verification (e.g., calibration plot, receiver operating characteristic analysis, decision curve analysis, and clinical impact curve analysis) in the development and validation cohorts, respectively. With threshold of scores of 100.3 and 176.8 before and after surgery respectively, both nomograms were able to stratify patients into two distinct prognostic subgroups (all p < 0.05).

Conclusion

The present study proposed two nomogram models integrating presurgical CTC counts and clinicopathological risks and showed relatively good predictive performance of EHR, which may be beneficial to the clinical practice of HCC recurrence. Further multicenter studies are needed to assess its general applicability.
Fast Feet Forward: A sports group for looked‐after children and unaccompanied asylum‐seeking children as an early intervention to process trauma and reduce distress
Authors: Draper Ana , Marcellino Elisa , Benham Kate , Dunn Zach David
Published: June 2023

Looked‐after children (LAC) and unaccompanied asylum‐seeking children (UASC) are likely to have experienced adverse childhood experiences (ACEs) in their developmental years, leading to poorer outcomes in their health and psychosocial development. A novel, exercise‐based early intervention utilising bilateral movements for UASC and adoptive children (An early intervention framework for the emotional health and wellbeing of unaccompanied minors, 2020) called Fast Feet Forward (FFF) has shown promise in providing relief from trauma symptoms. This study seeks to replicate the effectiveness of FFF and extend it to a new population of traumatised children. Two groups of FFF occurred with 18 children participating. Results revealed a statistically significant decrease in distress and an increase in positive cognitions for UASC, showing effective processing of trauma‐related hotspots. The LAC cohort also demonstrated a statistically significant decrease in distress and disturbance. Support is demonstrated for the efficacy of FFF as a cost‐effective and resiliency‐building early intervention treatment utilising bilateral movements for traumatised populations, especially UASC.
Abdominal aortic aneurysm presenting to the orthopedic clinic as posterior hip and low back pain
Authors: Marcel Aaron , Jovan John , Myrick Karen
Published: June 2023

Key Clinical Massage

Abdominal aortic aneurysms (AAAs) are typically asymptomatic. When symptomatic, AAA may present as a chief concern of musculoskeletal hip and low back pain. Assessment in the orthopedic clinic should focus on a holistic examination of the patient.
How to differentiate between invasive lobular carcinoma metastasis and type 4 advanced gastric cancer: The importance of immunohistochemistry
Authors: Jinushi Ryuhei , Kawasaki Tomonori , Ryozawa Shomei
Published: June 2023

Key Clinical Message

Gastric metastases derived from breast carcinomas and type 4 advanced gastric cancers are often difficult to distinguish because of their similar endoscopic and pathologic findings. Therefore, immunohistochemical analyses are key to diagnosis.

Gastric metastases originating from breast carcinomas and type 4 advanced gastric cancers are often difficult to distinguish because of their similar endoscopic and pathologic characteristics. This often delays early intervention and accordingly affects prognosis. Immunohistochemical analyses are important for both diagnosis and treatment of breast carcinomas.
Generalized tetanus in a farmer following treatment of an open ankle fracture by a traditional bone setter
Authors: Boi‐Dsane Naa Adzoa Adzeley , Seidu Anwar Sadat , Buunaaim Alexis Dun Bo‐ib
Published: June 2023

Key Clinical Message

This is the case of a 31‐year‐old farmer diagnosed with an open right ankle fracture and tetanus sustained from an accident after opting for traditional bonesetter treatment. Open fractures increase the risk of tetanus infection therefore herbal treatment should be discouraged. Source control is important for holistic management of tetanus.
Primary breast squamous cell carcinoma: A case report at a tertiary hospital in Northern Tanzania
Authors: Mremi Alex , Mwakyembe Theresia , Wampembe Elizabeth , Serventi Furaha , Lodhia Jay
Published: June 2023

Key Clinical Message

Primary SCC of the breast is a very rare disease.

Metastasis from elsewhere should be excluded first.

The tumor is a very aggressive with poor prognosis.

No standard treatment approaches are available.

Managed by surgical excision followed by chemotherapy and radiotherapy.

Primary squamous cell carcinoma of the breast is an exceedingly rare disease, and its management is still unclear. A‐65‐year‐old lady presented with a progressive swelling of her right breast that started spontaneously. Other potential primary sites were ruled out. She was kept on a neo‐adjuvant chemotherapy (AC‐T protocol) of doxorubicin, adriamycin, and paclitaxel. Later, she was underwent modified radical mastectomy with axillary lymph node dissection. Her post‐operative recovery was uneventful. Currently, she is followed up at oncology outpatient clinic.
Agitation and somnolence by bilateral paramedian thalamic infarct
Authors: Sheikh Hassan Mohamed , Osman Sidow Nor , Mohamed Ali Abdiladhif , Osman Mohamed Farah , Ahmed Ibrahim Abdiwahid , Abdirahman Ahmed Said
Published: June 2023

Key Clinical Message

Bilateral thalamic infarction in paramedian artery territory may present with severe acute illness, confusion, coma and memory impairment. However, subtle clinical presentation as in our case should alert the clinician to consider such a diagnosis as it can be associated with good prognosis.

Bilateral thalamic infarct is a rare form of stroke. Mostly thalamic infarcts are unilateral. In most cases, bilateral thalamic infarction leads to cognitive dysfunction, opthalmoparesis, conscious impairment, behavioral disturbance, and corticospinal dysfunction. Here, we describe the case of a 75‐year‐old male patient who presented to the emergency department of our hospital with agitation and somnolence for one day. He had poorly controlled hypertension. There was no previous history of stroke, diabetes mellitus, hyperlipidemia, known cardiac disease, or smoking history. There was no seizure, recent headache, or visual disturbance. The patient was somnolent and not oriented to time, person, or place. Neurological examination did not show any focal weakness or vertical eye movement restrictions. Other systemic examinations, including those of the respiratory and cardiovascular systems, were unremarkable. Extensive laboratory investigations excluded potential metabolic, infectious, endocrine, or toxic etiologies. The patient did not have any recent history of drug misuse, including benzodiazepines. Brain MRI with diffusion‐weighted imaging showed an acute bilateral thalamic infarct. Cerebral angiography was unremarkable. The patient was treated with low molecular weight heparin 60 mg subcutaneously, aspirin 300 mg daily, and haloperidol 5 mg twice daily for agitation. After two weeks of intrahospital treatment, his condition improved (consciousness and orientation massively improved).
A qualitative study on lived experience of self‐harm in South Asians in the UK: From reasons to recovery
Authors: Özen‐Dursun Büşra , Panagioti Maria , Alharbi Reem , Giles Sally , Husain Nusrat
Published: June 2023

Objectives

Self‐harm rates and clinical presentations differ by ethnicity. South Asian women are at risk of self‐harm. Previous research suggested investigating individuals' experiences with self‐harm with qualitative studies in developing self‐harm prevention strategies. This research aims to explore self‐harm experiences among South Asians in the United Kingdom.

Design

Qualitative study.

Methods

Participants were recruited via third‐sector organizations and online platforms. Semi‐structured interviews were conducted with 11 South Asian individuals with a history of self‐harm living in the United Kingdom. The data were analysed based on a reflective thematic analysis approach.

Results

Results revealed four main themes: (1) reasons for self‐harm; (2) recovery journey; (3) culture and mental health; and (4) the transition to suicidal thoughts and behaviours. Reasons for self‐harm included negative life circumstances, social life difficulties, challenges faced during COVID‐19 and mental health problems. Participants described their recovery journey by acknowledging the role of professional help, self‐care, psychoeducation and personal growth, improving social relationships, and faith and spirituality. Cultural factors included generational differences and stigma. Culturally adapted psychological interventions were perceived as promising. The reported transition from self‐harm to suicidal behaviours was linked to experiencing major stressful life events and the use of severe methods of self‐harm.

Conclusions

The findings suggest that socio‐cultural factors impact mental health and recovery processes among South Asians. Mental health services should consider improving culturally sensitive clinical practices in responding to self‐harm among South Asian communities.