bluuebunny/crossref_metadata_2025 huggingface dataset:
Urbanidades em construção: crianças, fotografias, falas e fábulas sobre a cidade
Authors: Alves Evandro , Marques Abreu Bárbara Cecília
Published: August 2018

Este artigo tem como objetivo refletir sobre os discursos das crianças sobre a cidade no contexto de um projeto pedagógico de uma turma de educação infantil de uma escola do munícipio de Porto Alegre (Brasil). Este projeto pedagógico, entre suas atividades, permitiu a produção de registros fotográficos, feitos pelas crianças, dos passeios e espaços que visitaram. Buscamos compreender, com a análise dessas produções, o entendimento das crianças sobre o espaço que as rodeia e as relações existentes nesse espaço. Para alcançar esse objetivo, os pesquisadores acompanharam as atividades de um projeto pedagógico sobre ocupação do espaço urbano, tipos de moradia e relações dos moradores da cidade. Este projeto resulta de uma articulação entre a professora de uma escola de educação infantil e os pesquisadores. Deste contexto, realizamos uma pesquisa qualitativa e exploratória. Imagens e discursos produzidos por crianças neste momento, em primeiro plano, aliadas a notas de campo dos pesquisadores, como pano de fundo, formam o contexto de produção dos dados desta investigação. Os resultados parciais desta pesquisa ainda em andamento apontam para: (1) diversidade das perspectivas das crianças sobre a cidade e vivendo na cidade; (2) muitas vezes essas perspectivas são diversas do ponto de vista dos adultos. Tal diversidade poderia, em princípio, estar relacionada: (3) à atividade de construção e criação do pensamento e subjetividade da criança para se apropriar e ressignificar o espaço urbano e suas relações.
Effects of Iodine Agronomic Bio- fortification on selected Physiological Characteristics of Cassava in Calabar, Southeastern Nigeria
Authors: J. E. O Ansa, , W. B. Binang,
Published: August 2018

Field experiments were conducted between November 2011 and May 2014 at the Crop Science Teaching and Research Farm of the University of Calabar, (Southeastern rainforest agro-ecological zone of Nigeria) to determine the effectiveness of Iodine agronomic fortification of cassava. The field experiment was a 2x3x4 factorial experiment arranged in randomized complete block design replicated three times, conducted using two cassava varieties,( TME 419 and TMS 30555); four iodine rates( 0, 2.5, 5.0 and 10.0) kg/ha KI; applied at 8, 10 and 12 WAP. Physiological data were obtained by determination of Iodine content [in cassava tuber]; tuber cyanide content (HCN); Carbohydrate content of tuber; starch content of tuber and tuber protein contents. Iodine absorption and retention in cassava tuber flesh was significantly positively correlated with Iodine doses at the times of application (p0.05 and 0.01). TME 419 retained more Iodine in tissues than TMS 30555 and recorded highest correlation co-efficient at 10WAP. Iodine doses and time of application did not significantly control (P≥0.05) contents of cyanide, carbohydrate and starch in cassava tubers. Protein content was significantly varied in cassava varieties and rate and time of Iodine application influenced tuber protein content. TME 419 produced more tuber protein, Iodine doses of 2.5kg/ha KI and 0kg/ha KI had higher protein content than 5kg and 10kg/ha KI. Application at 8WAP and 10WAP were not significantly different. For favourable physiological cassava characteristics, 2.5kg/ha KI is recommended applied 10 weeks after planting (WAP).
Fraternidad, conflicto y realismo político. Claves para pensar la integración desde América Latina
Authors: Del Percio Enrique
Published: August 2018

En el origen de la ciudad está el fratricidio: Caín y Abel, Rómulo y Remo y tantos otros ejemplos. Por eso, a partir de la Fraternidad como piedra angular de la teoría política es factible elaborar un marco de análisis y propuestas que asuman al conflicto como inherente a la condición humana. Si el vicio propio de la libertad es el egoísmo y el de la igualdad es la envidia, el de la fraternidad son los celos que sienten los hermanos. Así como el egoísmo hace referencia a la existencia de uno mismo y la envidia a la existencia del otro envidiado, los celos hacen referencia a un tercero. Esta referencia al tercero permite pensar la política como búsqueda experimental de una justicia necesariamente provisoria.TEORÍA Y PRAXIS año 10, No.21, Junio-Diciembre de 2012, pp.3-35
Experimenting With Academic ESL: An ESL/Sociology Link
Authors: August Gail
Published: August 2018

To improve academic ESL, a community college has been experimenting with linking an ESL class to a Sociology class. The primary goal was to use the methodology of Content Based Instruction to develop a curriculum that would promote academic vocabulary acquisition, critical thinking, and authentic communication in a sheltered environment. The paradigm of Action Research was used as a framework to reflect on the strengths of the program and to identify activities that engaged the students and contributed to improved language skills. Supplementary assignments of a Young Adult novel and provocative movies, used across both the ESL and Sociology class, helped students to apply abstract concepts to familiar situations. The structure of the link produced an effective learning community and a support system for the students. We suggest that linking ESL to a content course might be preferable to other options for developmental ESL students entering college.
The Need Analysis of Maritime English Learning Materials for Nautical Students of Maritime Academy in Indonesia Based on STCW’2010 Curriculum
Authors: Dirgeyasa I Wy
Published: August 2018

This study was aimed to investigate the Maritime English learning materials needed by the students of nautical department of Maritime Academy in Indonesia based in STCW’2010 curriculum. The participants of the research were the seafarers, the port authorities, the shipping business employees, the English lecturers, and the cadets of Maritime Academy. They were totally about 48 participants. They were selected by using purposive random sampling technique. There were three types of instruments for collecting data those were questionaire, documentary sheet, and interview. The results of the study shows that 1) there were three basic leaning materials categories of Maritime English namely a) the nautical contents, b) language skills, and c) languistic features and 2) the level of needs of those materials were different from categories to another categories and within categories.
Nuclear pore heterogeneity influences HIV-1 infection and the antiviral activity of MX2
Authors: Kane Melissa , Rebensburg Stephanie V , Takata Matthew A , Zang Trinity M , Yamashita Masahiro , Kvaratskhelia Mamuka , Bieniasz Paul D
Published: August 2018

HIV-1 accesses the nuclear DNA of interphase cells via a poorly defined process involving functional interactions between the capsid protein (CA) and nucleoporins (Nups). Here, we show that HIV-1 CA can bind multiple Nups, and that both natural and manipulated variation in Nup levels impacts HIV-1 infection in a manner that is strikingly dependent on cell-type, cell-cycle, and cyclophilin A (CypA). We also show that Nups mediate the function of the antiviral protein MX2, and that MX2 can variably inhibit non-viral NLS function. Remarkably, both enhancing and inhibiting effects of cyclophilin A and MX2 on various HIV-1 CA mutants could be induced or abolished by manipulating levels of the Nup93 subcomplex, the Nup62 subcomplex, NUP88, NUP214, RANBP2, or NUP153. Our findings suggest that several Nup-dependent ‘pathways’ are variably exploited by HIV-1 to target host DNA in a cell-type, cell-cycle, CypA and CA-sequence dependent manner, and are differentially inhibited by MX2.
Cortical dynein pulling mechanism is regulated by differentially targeted attachment molecule Num1
Authors: Omer Safia , Greenberg Samuel R , Lee Wei-Lih
Published: August 2018

Cortical dynein generates pulling forces via microtubule (MT) end capture-shrinkage and lateral MT sliding mechanisms. In Saccharomyces cerevisiae, the dynein attachment molecule Num1 interacts with endoplasmic reticulum (ER) and mitochondria to facilitate spindle positioning across the mother-bud neck, but direct evidence for how these cortical contacts regulate dynein-dependent pulling forces is lacking. We show that loss of Scs2/Scs22, ER tethering proteins, resulted in defective Num1 distribution and loss of dynein-dependent MT sliding, the hallmark of dynein function. Cells lacking Scs2/Scs22 performed spindle positioning via MT end capture-shrinkage mechanism, requiring dynein anchorage to an ER- and mitochondria-independent population of Num1, dynein motor activity, and CAP-Gly domain of dynactin Nip100/p150Glued subunit. Additionally, a CAAX-targeted Num1 rescued loss of lateral patches and MT sliding in the absence of Scs2/Scs22. These results reveal distinct populations of Num1 and underline the importance of their spatial distribution as a critical factor for regulating dynein pulling force.
PIP2 depletion promotes TRPV4 channel activity in mouse brain capillary endothelial cells
Authors: Harraz Osama F , Longden Thomas A , Hill-Eubanks David , Nelson Mark T
Published: August 2018

We recently reported that the inward-rectifier Kir2.1 channel in brain capillary endothelial cells (cECs) plays a major role in neurovascular coupling (NVC) by mediating a neuronal activity-dependent, propagating vasodilatory (hyperpolarizing) signal. We further demonstrated that Kir2.1 activity is suppressed by depletion of plasma membrane phosphatidylinositol 4,5-bisphosphate (PIP2). Whether cECs express depolarizing channels that intersect with Kir2.1-mediated signaling remains unknown. Here, we report that Ca2+/Na+-permeable TRPV4 (transient receptor potential vanilloid 4) channels are expressed in cECs and are tonically inhibited by PIP2. We further demonstrate that depletion of PIP2 by agonists, including putative NVC mediators, that promote PIP2 hydrolysis by signaling through Gq-protein-coupled receptors (GqPCRs) caused simultaneous disinhibition of TRPV4 channels and suppression of Kir2.1 channels. These findings collectively support the concept that GqPCR activation functions as a molecular switch to favor capillary TRPV4 activity over Kir2.1 signaling, an observation with potentially profound significance for the control of cerebral blood flow.
Frailty Trajectories Preceding Dementia in the US and UK
Authors: Ward David D. , Flint Jonny P. , Littlejohns Thomas J. , Foote Isabelle F. , Canevelli Marco , Wallace Lindsay M. K. , Gordon Emily H. , Llewellyn David J. , Ranson Janice M. , Hubbard Ruth E. , Rockwood Kenneth , Stolz Erwin
Published: November 2024

Importance

An accessible marker of both biological age and dementia risk is crucial to advancing dementia prevention and treatment strategies. Although frailty is a candidate for that role, the nature of the relationship between frailty and dementia is not well understood.

Objective

To clarify the temporal relationship between frailty and incident dementia by investigating frailty trajectories in the years preceding dementia onset.

Design, Setting, and Participants

Participant data came from 4 prospective cohort studies: the English Longitudinal Study of Ageing, the Health and Retirement Study, the Rush Memory and Aging Project, and the National Alzheimer Coordinating Center. Data were collected between 1997 and 2024 and were analyzed from July 2023 to August 2024. The settings were retirement communities, national-level surveys, and a multiclinic-based cohort. Included individuals were 60 years or older and without cognitive impairment at baseline. Included individuals also had data on age, sex, education level, and ethnicity and a frailty index score calculated at baseline.

Exposure

Frailty was the main exposure, with participants’ degrees of frailty quantified using retrospectively calculated frailty index scores.

Main Outcomes and Measures

Incident all-cause dementia ascertained through physician-derived diagnoses, self- and informant-report, and estimated classifications based on combinations of cognitive tests.

Results

The participant number before exclusions was 87 737. After exclusions, data from 29 849 participants (mean [SD] age, 71.6 [7.7] years; 18 369 female [62%]; 257 963 person-years of follow-up; 3154 cases of incident dementia) were analyzed. Bayesian generalized linear mixed regression models revealed accelerations in frailty trajectories 4 to 9 years before incident dementia. Overall, frailty was positively associated with dementia risk (adjusted hazard ratios [aHRs] ranged from 1.18; 95% CI, 1.13-1.24 to 1.73; 95% CI, 1.57-1.92). This association held among participants whose time between frailty measurement and incident dementia exceeded the identified acceleration period (aHRs ranged from 1.18; 95% CI, 1.12-1.23 to 1.43; 95% CI, 1.14-1.80).

Conclusions and Relevance

These findings suggest that frailty measurements may be used to identify high-risk population groups for preferential enrolment into clinical trials for dementia prevention and treatment. Frailty itself may represent a useful upstream target for behavioral and societal approaches to dementia prevention.
Epileptiform Electrographic Patterns After Cardiac Arrest
Authors: Rossetti Andrea O. , Benghanem Sarah
Published: November 2024

This Viewpoint challenges conventional clinical practice that eschews pharmacological intervention for comatose patients with epileptiform abnormalities after cardiac arrest using evidence from the Treatment of Electroencephalographic Status Epilepticus after Cardiopulmonary Resuscitation (TELSTAR) trial.
Understanding and measuring mechanical signals in the tumor stroma
Authors: de la Jara Ortiz Fàtima , Cimmino Chiara , Ventre Maurizio , Cambi Alessandra
Published: November 2024

The tumor microenvironment (TME) is well known for its immune suppressive role, especially in solid tumors which are characterized by a thick, dense stroma. Apart from cell–cell interactions and biochemical signals, the tumor stroma is also characterized by its distinct mechanical properties, which are dictated by the composition and architecture of its extracellular matrix (ECM). Cancer‐associated fibroblasts (CAFs) are the main producers and remodelers of the stromal ECM, and their heterogeneity has recently become a focus of intense research. This review describes recent findings highlighting CAF subtypes and their specific functions, as well as the development of 3D models to study tumor stroma mechanics in vitro. Finally, we discuss the quantitative techniques used to measure tissue mechanical properties at different scales. Given the diagnostic and prognostic value of stroma stiffness and composition, and the recent development of anti‐tumor therapeutic strategies targeting the stroma, understanding and measuring tumor stroma mechanical properties has never been more timely or relevant.
Peptide‐Guided Self‐Assembly: Fabrication of Tailored Spiral‐Like Nanostructures for Precise Inorganic Templating
Authors: Alvarez‐Fernandez Alberto , Pawar Nisha , Sanchez‐Puga Pablo , Zaccai Nathan. R. , Maestro Armando
Published: November 2024

Self‐assembling peptides (SAPs) are versatile building blocks in the creation of hierarchical nanostructures. Although SAPs promise precise control over assembled morphology and dimensions, experimental validation is still crucial. In this sense, recent efforts have focused on nanospiral structures, which mimic natural architectures and hold potential for biomedical and nanotechnological applications. Here, it is demonstrated that SARS‐CoV‐2 fusion peptides are able to form specific spiral‐like structures using interfacial assembly as a fabrication methodology, along with fine‐tuning of the spiral ensembles through an imposed interfacial flow due to the uniaxial compression in a Langmuir–Blodgett trough. Molecular characterization by atomic force microscopy, neutron reflectometry, interfacial shear rheology, and infrared spectroscopy, highlighted how variations in fusion peptide sequences influence assembly, highlighting the importance of molecular design. These spiral structures are subsequently modified to serve as templates for metallic replicas, expanding the potential of peptide‐guided self‐assembly in fabricating tailored nanostructured surfaces with sub‐10 nm dimensions over cm2 areas.
Flexible Piezoelectric Energy Harvesters with Mechanoluminescence for Mechanical Energy Harvesting and Stress Visualization Sensing
Authors: Fu Xueting , Cao Yongquan , Song Xinyue , Sun Renbing , Jiang Hai , Du Peng , Peng Dengfeng , Luo Laihui
Published: November 2024

Flexible piezoelectric energy harvesters (FPEHs) have wide applications in mechanical energy harvesting, portable device driving, and piezoelectric sensors. However, the poor output performance of piezoelectric energy harvesters and the intrinsic shortcoming of piezoelectric sensors that can only detect dynamic pressure limit their further applications. BaTiO3 (BT) and PVDF are deposited on the glass fiber electronic cloth (GFEC) by impregnation and spin‐coating methods, respectively, to form BT‐GFEC/PVDF piezoelectric composite films. A mixed solution of mechanoluminescence (ML) particles ZnS:Cu and PDMS are used as the encapsulation layer to construct a high‐performance ML‐FPEH with self‐powered electrical and optical dual‐mode response characteristics. Due to the interconnection structure of the piezoelectric films, the prepared ML‐FPEH illustrates a high effective energy harvesting performance (≈58 V, ≈43.56 µW cm−2). It can also effectively harvest mechanical energy from human activities. More importantly, ML‐FPEH can sense stress distribution of hand‐writing via ML to achieve stress visualization, making up for the shortcomings of piezoelectric sensors. This work provides a new strategy for endowing FPEH with dual‐mode sensing and energy harvesting.
Spontaneous Phase Transition and Multistage Interfacial Mechanical Friction of Liquid Metals Induced CO2 Reduction at Room Temperature
Authors: Luo Hanhai , Zhang Liyuan , Yang Huiqin , Yang Wen , Liu Qingju , Mu Weihua , Boudmyxay Khampheng , Liu Jing , Yang Peizhi , Duan Liangfei
Published: November 2024

Excessive emissions of carbon dioxide (CO2) have caused the greenhouse effect and environmental crisis. Therefore, the carbon reduction and negative carbon technologies are particularly important. Among these, the negative carbon technologies that convert CO2 into carbon materials or carbon‐based chemicals for reuse have attracted significant attention. However, the strong double covalent bonds make the CO2 conversion usually require harsh conditions, complex processes, and high energy consumption. Gallium‐based liquid metals (LMs) are the functional materials with both metallic and liquid properties, exhibiting a unique liquid‐phase structure and diverse surface characteristics. Herein, a strategy for reducing CO2  is proposed to carbon materials by utilizing the spontaneous phase transition and mechanical friction of liquid metals. The gallium (Ga) and indium (In) particles are mixed and exposed to CO2, the contact interface of metal particles spontaneously transforms into liquid metals. The system has multistage interfaces, including Ga/In, Ga/eGaIn, and In/eGaIn, capable of generating triboelectrification upon mechanical stimulation, leading to charge transfer. The high electric field generated by friction at the contact interface directly reduces CO2 to carbon materials at room temperature. The carbon materials cover the surface of eGaIn and can be directly stripped for used as fuel, or industrial applications.
Simultaneous Modulation on Solvation Shell and Electrode Interface for Reversible Zinc Anode Realized by a Mutiplefunctional Additive
Authors: Cao Zhaoxia , Ma Xiaofeng , Liu Wenxuan , Wu Jiarou , Jiao Yujie , Yin Yanhong , Lu Zhansheng , Yang Shuting
Published: November 2024

The inferior reversibility of Zn metal anode caused by undesired Zn dendrite and severe interfacial side reactions has to be addressed for the commercial application of Zinc ion batteries (ZIBs). Here, a multiple functional sodium benzaldehyde 2,4‐disulfonate(B24DADS) additives with various blocks of polar sulfonate group, Lewis basic aldehyde groups, and hydrophobic benzene ring is proposed to regulate the solvation structure of Zn2+, construct an H2O‐poor and zincophilic dual electric layer structure, and create a passive SEI on the Zn anode surface, thus restaining dendrite growth and interfacial side reactions. Furthermore, uniform deposition mechanics of the Zn are revealed by the synergistic effect of induced deposition, additive‐derived SEI formation, and texture regulation. In addition, Na+ can also limit the growth of zinc dendrites based on electrostatic shielding mechanisms. Therefore, the multifunctional B24DADS additive grants the anode to deliver remarkable electrochemical performance. Under critical test conditions (20 mA cm−2/20 mAh cm−2), the zinc provides superior long cycling (3700 h) with a low polarization voltage (0.02 V). B24DADS containing electrolyte is well matched with manganese dioxide cathode. This effort renders a promising way to explore advanced additives with unique molecular structures for addressing zinc dendrite growth and rampant side effects.
Inflammation‐Responsive Functional Core–Shell Micro‐Hydrogels Promote Rotator Cuff Tendon‐To‐Bone Healing by Recruiting MSCs and Immuno‐Modulating Macrophages in Rats
Authors: Chen Baojun , Zhao Xin , Xu Meiguang , Luo Jinlong , Bai Lang , Han Qian , Gao Yanzheng , Guo Baolin , Yin Zhanhai
Published: November 2024

Rotator cuff injuries often necessitate surgical intervention, but the outcomes are often unsatisfactory. The underlying reasons can be attributed to multiple factors, with the intricate inflammatory activities and insufficient presence of stem cells being particularly significant. In this study, an innovative inflammation‐responsive core–shell micro‐hydrogel is designed for independent release of SDF‐1 and IL‐4 within a single delivery system to promote tendon‐to‐bone healing by recruiting MSCs and modulating M2 macrophages polarization. First, a MMP‐2 responsive hydrogel loaded with IL‐4 (GelMA‐MMP/IL‐4) is synthesized by cross‐linking gelatin methacrylate (GelMA) with MMP‐2 substrate peptide. Then, the resulting core particles are coated with a shell of chitosan /SDF‐1/hyaluronic acid (CS/HA/SDF‐1) using the layer‐by‐layer electrostatic deposition method to form a core–shell micro‐hydrogel composite. The core–shell micro‐hydrogel shows sustained release of SDF‐1 and MMP‐2‐responsive release of IL‐4 associated in situ MSCs homing and smart inflammation regulation by promoting M2 macrophages polarization. Additionally, by injecting these micro‐hydrogels into a rat rotator cuff tear and repair model, notable improvements of fibrocartilage layer are observed between tendon and bone. Notably, this study presents a new and potentially powerful environment‐responsive drug delivery strategy that offers valuable insights for regulating the intricate micro‐environment associated with tissue regeneration.
Use of in situ simulation to improve team performance and utilization of a rapid sequence intubation checklist
Authors: Waters Kathleen M. , Hwu Ruth , Kulkarni Mona , Okonye Jeffrey , Zamor Ronine , Chaudhary Sofia , Jergel Andrew , Gillespie Scott , Lewis Abby , Krieger Rachel , Menon Vidya , Bell Geovonni , Levy Jacob , Prynn Tory , Regan Jacqueline , Mathai Claire , Goodwin Nandranie , Holmes Sherita
Published: November 2024

Background

Intubation checklists have emerged as tools to reduce adverse events and improve efficiency during rapid sequence intubation (RSI) in pediatric emergency departments (PEDs). This study aimed to use multidisciplinary simulation (SIM) training as an educational tool to improve PED team performance during RSI scenarios through utilization of an RSI checklist.

Methods

We created a checklist modeled after previously published PED checklists. PED multidisciplinary teams participated in video‐recorded SIM training sessions involving a scenario requiring intubation three times, first without interruption then while receiving our intervention of rapid‐cycle deliberate practice (RCDP) debriefing focusing on checklist utilization and team dynamics. Learners went through the scenario once more uninterrupted to apply learned skills. Team performance was evaluated via video review using the Simulation Team Assessment Tool (STAT) focusing on airway management and human factors sections. Scores were compared before and after intervention along with pre‐ and postintervention surveys.

Results

A total of 483 learners participated in 64 SIM training sessions, 44 of whom met inclusion criteria and were included for data analysis. Scores increased postintervention for airway management, human factors and in total. Least‐squares mean differences for total, airway, and human factors scores were 9.55 (95% confidence interval [CI] 7.24–11.85), 4.22 (95% CI 2.91–5.52), and 5.33 (95% CI 3.86–6.8), respectively, which was statistically significant with p‐value of <0.001 across all categories. Surveys demonstrated improved role understanding and checklist utilization comfort postintervention.

Conclusions

This study supports the benefit of multidisciplinary SIM training with RCDP‐style methodology as an educational method for improving airway management, teamwork skills, and RSI checklist utilization for PED staff. Incorporation of additional maintenance SIM sessions for ongoing education is likely to be further beneficial and would allow evaluation of degradation of skills over time following initial training.
Machine Learning‐Based Wind Classification by Wing Deformation in Biomimetic Flapping Robots: Biomimetic Flexible Structures Improve Wind Sensing
Authors: Kubota Kenta , Tanaka Hiroto
Published: November 2024

Flying animals such as insects and birds have strain receptors on their wings. The functions and information processing capabilities of these strain receptors, however, are largely unknown. Herein, the potential ability of wing strain sensors to detect wind direction in flapping flight is experimentally explored. Seven strain gauges are attached to the biomimetic wing shafts of flexible wings. The wings flap through an electric mechanism emulating hovering flight in a wind tunnel with gentle wind, and a convolutional neural network model for wind direction classification is developed. The results show that with only one strain gauge, accurate wind classification is achieved using segmented data of ≈1 flapping cycle. Even with segmented data of only 0.2 flapping cycles, wind classification can be achieved with all seven strain gauges. Moreover, the use of wing shafts improves the classification accuracy, especially with shorter segmented data. Additional flapping phase information does not substantially improve classification performance. These results suggest that hovering animals determine the wind direction via strain sensing, which is useful for flight control. The implementation of wing strain sensors in flapping‐wing aerial robots may improve flight control ability.
Synthesis of 2‐Substituted‐4,5‐Dihydrothiazol‐4‐Ols by [3+2] Annulation of 1,4‐Dithiane‐2,5‐Diol with Thioamides
Authors: Zhang Mengcheng , Chen Yuying , Liu Jiayu , Yan Xiaoyu , Huang Kexin , Ma Xiantao
Published: November 2024

We developed a novel method for the synthesis of 2‐substituted‐4,5‐dihydrothiazol‐4‐ols compounds through cyclization of thioamides and 1,4‐dithiane‐2,5‐diol in the presence of Et3N. Stable hydroxy‐substituted thiazole compounds were isolated of substituted thioamides. The reaction conditions are simple, the substrate range is wide, and the target compounds were obtained in up to 82 % yield.
A Detailed View on the (Re)isomerization Dynamics in Microbial Rhodopsins Using Complementary Near‐UV and IR Readouts
Authors: Asido Marvin , Lamm Gerrit H. U. , Lienert Jonas , La Greca Mariafrancesca , Kaur Jagdeep , Mayer Anne , Glaubitz Clemens , Heberle Joachim , Schlesinger Ramona , Kovalev Kirill , Wachtveitl Josef
Published: November 2024

Isomerization is a key process in many (bio)chemical systems. In microbial rhodopsins, the photoinduced isomerization of the all‐trans retinal to the 13‐cis isomer initiates a cascade of structural changes of the protein. The interplay between these changes and the thermal relaxation of the isomerized retinal is one of the crucial determinants for rhodopsin functionality. It is therefore important to probe this dynamic interplay with chromophore specific markers that combine gapless temporal observation with spectral sensitivity.

Here we utilize the near‐UV and mid‐IR fingerprint region in the framework of a systematic (time‐resolved) spectroscopic study on H+‐ (HsBR, (G)PR), Na+‐ (KR2, ErNaR) and Cl−‐(NmHR) pumps. We demonstrate that the near‐UV region is an excellent probe for retinal configuration and—being sensitive to the electrostatic environment of retinal—even transient ion binding, which allows us to pinpoint protein specific mechanistic nuances and chromophore‐charge interactions. The combination of the near‐UV and mid‐IR fingerprint region hence provides a spectroscopic analysis tool that allows a detailed, precise and temporally fully resolved description of retinal configurations during all stages of the photocycle.
The Kinetics of Carbon‐Carbon Bond Formation in Metazoan Fatty Acid Synthase and Its Impact on Product Fidelity
Authors: Gusenda Christian , Calixto Ana R. , Da Silva Joana R. , Fernandes Pedro A. , Grininger Martin
Published: November 2024

Fatty acid synthase (FAS) multienzymes are responsible for de novo fatty acid biosynthesis and crucial in primary metabolism. Despite extensive research, the molecular details of the FAS catalytic mechanisms are still poorly understood. For example, the β‐ketoacyl synthase (KS) catalyzes the fatty acid elongating carbon‐carbon‐bond formation, which is the key catalytic step in biosynthesis, but factors that determine the speed and accuracy of his reaction are still unclear. Here, we report enzyme kinetics of the KS‐mediated carbon‐carbon bond formation, enabled by a continuous fluorometric activity assay. We observe that the KS is likely rate‐limiting to the fatty acid biosynthesis, its kinetics are adapted to the length of the bound fatty acyl chain, and that the KS is also responsible for the fidelity of biosynthesis by preventing intermediates from undergoing KS‐mediated elongation. To provide mechanistic insight into KS selectivity, we performed computational molecular dynamics (MD) simulations. We identify positive cooperativity of the KS dimer, which we suggest to affect the conformational variability of the multienzyme. Advancing our knowledge about the KS molecular mechanism will pave the ground for engineering FAS for biotechnology applications and the design of new therapeutics targeting the fatty acid metabolism.
Dynamically Switchable Global Chirality in Racemic Polymer Systems
Authors: He Zixiang , Guo Jiaying , Wang Yuqing , Ma Haotian , Cheng Xiaoxiao , Zhang Wei
Published: November 2024

Any polymers composed of racemic segments are obviously optically inactive and lack any chiroptical applications. Here, we present an intriguing method for precisely generating global chirality in racemic copolymer assemblies without any external asymmetrical intervention via step‐wise polymerization‐induced chiral self‐assembly (PICSA). Global supramolecular chirality of the nanoaggregates could be dynamically switched by the two diametrically opposed chiral conflict effects: “first come, first serve” effect and “late‐comer lives above” effect, which can be controlled by the precisely specified the number and sequence of enantiomeric segments. Significantly, the supramolecular stacking manners of the racemic mesogenic building units as well as the liquid crystallinity of the solvophobic core play a crucial role for the chiral communication pathway of enantiomeric mesogens. Furthermore, such switchable global chirality in racemic polymers is broadly applicable and well regulable. We propose that this research may challenge the notion that racemic systems lack optical activity while highlighting their potential applications in functional racemic polymer materials and providing insights into the evolution of racemates towards homochirality on early Earth.
Physical Isolation of Single Protein Molecules within Well‐Defined Coordination Cages to Enhance Their Stability
Authors: Ebihara Risa , Nakama Takahiro , Morishima Ken , Yagi‐Utsumi Maho , Sugiyama Masaaki , Fujita Daishi , Sato Sota , Fujita Makoto
Published: November 2024

Encapsulation of a single protein within a confined space can lead to distinct properties compared to bulk solutions, but controlling the number of encapsulated proteins and their environment remains challenging. This study demonstrates the encapsulation of single proteins within well‐defined, tunable cavities of self‐assembled coordination cages, thereby enhancing protein stability. Within uniform cavities of size‐tunable coordination cages, 15 different proteins of varying sizes (3–6 nm in diameter) and properties (e.g., isoelectric points and hydrophobicity) were successfully confined. Various analytical techniques confirmed that the proteins maintained their secondary structures and enzymatic activities under denaturing conditions such as exposure to organic solvents, heat, and buffers. These findings suggest that such coordination cages have the potential to serve as synthetic hosts for precisely controlling protein functions within their customizable cavities.
Impact of hydrothermal aging on microstructure transformation in Poly(L‐lactide) nonwovens under tension in condition close to a living organism
Authors: Morokov Egor , Tertyshnaya Yulia , Buzanov Grigorii
Published: November 2024

The analysis of mechanical properties and structure of bioresorbable polymer nonwoven materials is an important area of research in the medical industry, the properties and structure of which directly affect the processes of cellular activity. In this work, the processes of reorganization of the fibrous microstructure of poly(l‐lactide) nonwoven materials under uniaxial tension in a water environment were investigated. The study which included volumetric ultrasound imaging, mechanical testing, differential scanning calorimetry, X‐ray diffraction, and melting rate measurements was the first attempt to identify correlations between the mechanical behavior of fibrous meshes and changes in the supramolecular structure of the polymer during 3 months of hydrothermal aging T = 37°C. An increase in crystallinity by 4%, a shift of glass transition temperature by 4°C, and a 2 times increase in melt flow rate under hydrolysis were indicated degradation of the amorphous phase. Local degradation of the amorphous phase of fibers led to the formation of surface cracks, an increase in the number of microcracks during hydrothermal aging resulted in a decrease in the mobility of fibers in the volume of the nonwoven material and a decrease in the elasticity of the entire nonwoven material, which was revealed using the volume ultrasound imaging and optical microphotographs.
Organocatalytic Asymmetric Synthesis of C−N Atropisomers with Pyrrole, Oxindole and Succinimide Scaffold
Authors: Biswas Subhankar , Kundu Subham , Chandra Pan Subhas
Published: November 2024

An asymmetric synthesis of C−N atropisomers with pyrrole, oxindole and succinimide moities was developed via organocatalytic desymmetric Michael addition of 3‐pyrrolyloxindole with prochiral N‐aryl maleimides. The C−N atropisomers were obtained in acceptable yields with high diastero‐ and enantioselectivities (>20 : 1 dr, up to >99 % ee). C−N Rotational energy barrier has also been determined.
Prospective per‐target analysis of the added value of the PrecisionPoint Transperineal Access System in cognitive prostate biopsy of MRI targets
Authors: Orecchia Luca , Germani Stefano , Colalillo Gaia , Fasano Angelica , Ricci Matteo , Rosato Eleonora , Asimakopoulos Anastasios D. , Albisinni Simone , Finazzi Agrò Enrico , Manenti Guglielmo , Miano Roberto
Published: November 2024

Objectives

The objective of this study is to evaluate the diagnostic performance of perineal access cannulas tethered to a biplanar ultrasound probe in cognitive transperineal prostate biopsies of targets identified by multiparametric magnetic resonance imaging (mpMRI) by comparing the results of the PrecisionPoint (PP) Transperineal Access System with the double‐freehand (DFH) technique.

Patients and methods

All patients who underwent cognitive transperineal prostate biopsy of mpMRI targets using the PP or DFH technique between November 2020 and September 2023 were enrolled. All data related to mpMRI target biopsies were stratified by technique, visibility in transrectal ultrasound and analysed by comparing PP versus DFH. A standardised anaesthesia protocol with 1% mepivacaine was used in all biopsies. The tolerability of the procedures was assessed using a visual analogue scale (VAS).

Results

The number of mpMRI targets sampled was 166 in PP and 242 in DFH. In target biopsies, the PP system was associated with better diagnostic performance for clinically significant prostate cancer (Gleason score ≥3 + 4) compared to DFH for both ultrasound‐visible targets (61.4% vs. 48.0%) and non‐visible targets (41.4% vs. 14.9%) (p = 0.02). A higher rate of positive cores was obtained from targets sampled with PP (57.7% vs. 49.6%, p = 0.0002). The PP system was associated with the retrieval of significantly longer cores (p < 0.0001). There was no significant difference between the techniques regarding pain reported during the biopsy, with a median VAS of 2.7/10, although the PP device required a lower amount of anaesthetic in the periprostatic planes (4.3 ± 2.0 mL vs. 5.9 ± 1.9 mL, p < 0.0001).

Conclusion

The PrecisionPoint Transperineal Access System enabled more precise and higher quality biopsies, resulting in improved histological characterisation of prostate cancer compared to the DFH approach. The use of a perineal cannula did not increase the pain perceived by patients and also required less local anaesthetic during the biopsy.
The Efficacy and Safety of Folate Receptor α‐Targeted Antibody‐Drug Conjugate Therapy in Patients With High‐Grade Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers: A Systematic Review and Meta‐Analysis
Authors: Kim Eun Taeg , Kim Ji Hyun , Park Eun Young , Song In Hye , Park Han Song , Park Sang‐Yoon , Lim Myong Cheol
Published: November 2024

Background

Antibody‐drug conjugates (ADC) have emerged as a highly promising systemic option in the treatment of recurrent ovarian cancer. The present study aimed to evaluate the treatment efficacy of folate receptor α (FRα)‐targeting ADCs, associated treatment‐related adverse events (TRAEs), and their impact on treatment safety.

Methods

We conducted an electronic search to identify prospective trials of single‐agent ADCs targeting FRα and those combined with chemotherapy in recurrent ovarian cancer. Information regarding the objective response rate (ORR) and TRAEs was collectively analyzed, and differences in subgroups based on FRα receptor expression levels were investigated. The protocol was registered with PROSPERO (CRD42023491151).

Results

Ten studies with a total of 940 patients (859 treated with Mirvetuximab soravtansine‐gynx (MIRV)), 45 with Farletuzumab Ecteribulin (MORAb‐202), and 36 with Luveltamab Tazevibulin (STRO‐002) were included in this meta‐analysis. Based on the pooled data, the ORR of the entire cohort was 37% (95% CI: 0.30–0.43), while that of the high‐FRα expression group was 34% (95% CI: 0.26–0.42). The incidence of grade ≥ 3 adverse events was 27% (95% CI: 0.19–0.36).

Conclusion

FRα‐targeting ADCs, including MIRV, demonstrated definite efficacy and good safety as novel choices for second‐line and beyond treatment of advanced or recurrent ovarian cancer. Patients with high FRα expression showed ORR and PFS benefits similar to those in the overall cohort.
Combination Immunotherapy With Radiotherapy in Non‐Small Cell Lung Cancer: A Review of Evidence
Authors: Burr Justin L. , Johnson Kurtis C. , Carmicheal Joseph J. , Lin Chi , Ganti Apar Kishor
Published: November 2024

Background

Radiotherapy plays a fundamental role in the treatment of patients with all stages of non‐small‐cell lung cancer (NSCLC). The emergence of immune checkpoint inhibitors (ICIs) has transformed the standard of care in these patients. The use of ICIs is increasingly utilized in the definitive setting as an adjunct to chemoradiotherapy or surgery and remains a vital component in the treatment of metastatic disease. Despite improvements in patient survival, the use of immunotherapy as monotherapy has shown limited overall response rates with susceptibility to resistance. Radiotherapy has been identified as a viable option to enhance the response rate to ICI and improve outcomes in NSCLC.

Methods

We queried the English PubMed database utilizing variably combined search items including “radiation,” “chemoradiation,” “immune checkpoint,” “immunotherapy,” “stereotactic body radiotherapy,” and “non‐small‐cell lung”. We additionally searched various acceptable alternative terms for similar keywords such as “radiotherapy” in place of “radiation.” These results were subsequently curated for relevance and impact on current treatment paradigms.

Results

In this review, we discuss preclinical and clinical studies relating to combinatorial use of immunotherapy and radiation in NSCLC. These studies are presented in the context of early‐stage, operable stage III, unresectable stage III, and metastatic disease. The majority of the data illustrate promising results regarding the additive or synergistic effects of radiation and immunotherapy with a suggestion that the timing of these treatment modalities is crucial to optimizing outcomes.

Conclusion

While there is now evidence regarding the favorable interplay between radiation and immunotherapy in NSCLC, there remain multiple unanswered questions which are expected to be addressed in ongoing clinical trials.
Is Centralisation of Cancer Services Associated With Under‐Treatment of Patients With High‐Risk Prostate Cancer?—A National Population‐Based Study
Authors: Han Lu , Mayne Emily , Dodkins Joanna , Sullivan Richard , Cook Adrian , Parry Matthew , Nossiter Julie , Cowling Thomas E. , Tree Alison , Clarke Noel , van der Meulen Jan , Aggarwal Ajay
Published: November 2024

Background

Centralising prostate cancer surgical and radiotherapy services, requires some patients to travel longer to access treatment, but its impact on actual treatment utilisation and outcomes is unknown.

Methods

Using national cancer registry records linked to administrative hospital data, we identified all patients with high risk and locally advanced prostate cancer diagnosed between 1 April 2019 and 31 March 2020 in the English National Health Service (n = 15,971). Estimated travel times from the patient residential areas to the nearest hospital providing surgery or radiotherapy were estimated for journeys by car and by public transport. Multivariable logistic regression was used to model relationships between travel time and receipt of care with adjustment for patient characteristics.

Results

10,693 (67%) men received radical surgery or radiotherapy (RT) within 12 months of diagnosis. Average travel time to the nearest hospital providing prostatectomy or RT was 23.2 min by private car and 58.2 min by public transport. We found no association between travel time, either by car or public transport and the likelihood of receiving curative treatment. Patients living in the most socially deprived areas, those aged over 70, those with two or more comorbidities, and those of black ethnic origin, were less likely to receive curative treatment (p& =& 0.001 for all associations).

Conclusions

The current configuration of national prostate cancer services is not associated with the likelihood of receiving curative treatment. Further increases in capacity will unlikely improve utilisation rates beyond addressing sociodemographic barriers.
The modern role of paraprofessionals in delivering brief psychological interventions
Authors: Morrison Nicholas R. , Chang Mu‐Yin , Xie Alice , Kim Youngsuk
Published: November 2024

The increasing global demand for mental health services, compounded by the COVID‐19 pandemic, has spurred innovative approaches. Among these, the utilisation of paraprofessionals for delivering brief psychological interventions (BPIs) is gaining significant traction across diverse settings and populations. Paraprofessionals (individuals equipped with specialised mental health training but lacking formal qualifications) have emerged as a valuable resource. They have the potential to offer cost‐effective, culturally sensitive and readily accessible support. The integration of paraprofessionals into various healthcare settings, such as inpatient psychiatric units and primary care clinics, underscores their potential to enhance holistic well‐being and early intervention. This integration not only lightens the load on licensed therapists but also broadens access to services while reducing treatment costs. At a global scale, paraprofessionals, armed with local knowledge and community connections, play a pivotal role in improving mental health outcomes among underserved populations. Furthermore, the rise of telemental health, an increasingly crucial aspect of mental healthcare, presents new avenues for paraprofessionals to deliver psychological care. Despite their potential, paraprofessionals encounter challenges related to work‐life balance, boundary‐setting and the stigma attached to their roles. Their integration into healthcare systems requires clear roles and responsibilities, along with continuous support to ensure effective intervention and the well‐being of both providers and recipients. Further research and development are necessary to harness their full potential and meet the increasing demand for accessible mental health services.
Long‐Term Clinical Outcomes of Biodegradable‐ Versus Durable‐Polymer‐Coated Everolimus‐Eluting Stents in Real‐World Post‐Marketing Study
Authors: Abusnina Waiel , Case Brian C. , Zhang Cheng , Chitturi Kalyan R. , Sawant Vaishnavi , Chaturvedi Abhishek , Haberman Dan , Lupu Lior , Sutton Jospeh A. , Ali Syed W. , Deksissa Teshome , Pokharel Shreejana , Ozturk Sevket T. , Margulies Adrian , Ben‐Dor Itsik , Hashim Hayder D. , Satler Lowell F. , Garcia‐Garcia Hector M. , Waksman Ron
Published: November 2024

Background

Long‐term clinical data on biodegradable‐polymer (BP) drug‐eluting stents (DES) are limited. The objective of this study was to assess the long‐term safety and efficacy of the BP‐DES SYNERGY compared to XIENCE V, a durable‐polymer (DP)‐DES.

Methods

We compared patients treated with BP‐DES or DP‐DES at our center from 2008 to 2020. The primary outcome was major adverse cardiac events (MACE), defined as the composite of all‐cause death, Q‐wave myocardial infarction (MI), and target vessel revascularization (TVR). Secondary endpoints were all‐cause death, Q‐wave MI, target lesion revascularization (TLR), and stent thrombosis (ST).

Results

A total of 4255 patients underwent propensity‐score matching, and 380 patients from each cohort were matched. There was no significant difference between BP‐DES and DP‐DES concerning MACE (5‐year estimates: 21.6% vs. 26.6%, log‐rank p = 0.259). Furthermore, there was no difference in the TLR rate (5‐year estimates: 7.3% vs. 8.6%, log‐rank p = 0.781). All‐cause death (5‐year estimates: 13.6% vs. 12.9%, log‐rank p = 0.72) and Q‐wave MI (5‐year estimates: 0.53% vs. 1.7%, log‐rank p = 0.427) were also comparable between the two groups. Of note, the rate of very late ST was very low and similar between the groups (5‐year estimates: 0.26% vs. 0.64%, log‐rank p = 0.698).

Conclusion

BP‐DES and DP‐DES demonstrate similar safety and efficacy at 5‐year follow‐up. Both can be used for the effective treatment of coronary artery disease.