bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulating Size and Charge of Liposomes in Microneedles to Enhance Intracellular Drug Delivery Efficiency in Skin for Psoriasis Therapy
Authors: Qu Fei , Sun Yufeng , Bi Duohang , Peng Siyu , Li Min , Liu Hongmei , Zhang Lianbin , Tao Juan , Liu Yijing , Zhu Jintao
Published: September 2023

The stratum corneum (SC) and cell membrane are two major barriers that hinder the therapeutic outcomes of transdermal drug delivery for the treatment of skin diseases. While microneedles (MNs) can efficiently penetrate the SC to deliver nanomedicines, the optimization of physicochemical properties of nanomedicines in MNs to enhance their in vivo cellular delivery efficiency remains unclear. Here, how the size and surface charge of drug‐loaded liposomes in MNs influence the retention time and cellular delivery in psoriatic skin is systematically investigated. The results indicate that while 100 nm negatively‐charged liposomes in MNs show higher cellular uptake in vitro, 250 and 450 nm liposomes could enhance skin retention and the long‐term in vivo cellular delivery efficiency of drugs. Moreover, 250 nm cationic liposomes with a stronger positive charge show an extraordinarily long skin retention time of 132 h and significantly higher in vivo cellular internalization. In the treatment study, dexamethasone (dex)‐loaded cationic liposomes‐integrated MNs show better therapeutic outcomes than dex‐loaded anionic liposomes‐integrated MNs in a psoriasis‐like animal model. The design principles of liposomes in MN drug delivery systems explored in the study hold the potential for enhancing the therapeutic outcomes of psoriasis and are instrumental for successful translation.
Spatially Programmable Architected Materials Inspired by the Metallurgical Phase Engineering
Authors: Liu Chen , Pham Minh‐Son
Published: September 2023

Programmable architected materials with the capabilities of precisely storing predefined mechanical behaviors and adaptive deformation responses upon external stimulations are desirable to help increase the performance and the organic integration of materials with surrounding environments. Here, a new approach inspired by the physical metallurgical principles is proposed to allow the materials designers to not only enhance the global strength but also precisely tune mechanical properties (such as strength, modulus, and plastic deformation) locally in architected materials to create a new class of intelligent mechanical metamaterials. Such programmable materials not only have high strength and plastic deformation stability but also the ability to regulate the local deformation states and spatially control the internal propagation of deformation. This innovative approach also provides new and effective ways to enhance the adaptivity of the materials thanks to responsive strengths that not only make the materials increasingly stronger but also allow threshold‐based adaptive responses to external loading.
Fabrication of Au‐Decorated Al Nanoconcavities Platform for Augmented SERS
Authors: Dar Gohar Ijaz , Xifre‐Perez Elisabet , Marsal Lluis F.
Published: September 2023

A robust and competitive technology to synthesize arranged high‐density gold nanoparticles on highly uniform Al nanoconcavities substrates is presented. The nanoparticles are formed through sputtering and thermal annealing treatment on Al templates, which are synthesized through particular removal of nanoporous anodic alumina structure with controlled anodization conditions and with phosphoric acid as electrolyte. This scalable fabrication mechanism regulates the particle size, arrangement, shape and interparticle separation across large surface areas, which empowers the optimization of their surface enhanced Raman scattering (SERS) activities. 4‐mercaptopyridine is selected as a probe molecule. Analysis reveals that Au‐decorated Al nanoconcavities substrates are highly competitive for the enhancement of Raman signals and could be employed as self‐sustaining nanosensors. By using these templates, a concentration as low as 10−7 M of 4‐mercaptopyridine is easily detected. Finally, the calculated EF factor of 1.1 × 107 confirms the suitability for effective and sensitive SERS detection of the developed substrates.
Living Material with Temperature‐Dependent Light Absorption
Authors: Xiong Lealia L. , Garrett Michael A. , Kornfield Julia A. , Shapiro Mikhail G.
Published: September 2023

Engineered living materials (ELMs) exhibit desirable characteristics of the living component, including growth and repair, and responsiveness to external stimuli. Escherichia coli (E. coli) are a promising constituent of ELMs because they are very tractable to genetic engineering, produce heterologous proteins readily, and grow exponentially. However, seasonal variation in ambient temperature presents a challenge in deploying ELMs outside of a laboratory environment because E. coli growth rate is impaired both below and above 37 °C. Here, a genetic circuit is developed that controls the expression of a light‐absorptive chromophore in response to changes in temperature. It is demonstrated that at temperatures below 36 °C, the engineered E. coli increase in pigmentation, causing an increase in sample temperature and growth rate above non‐pigmented counterparts in a model planar ELM. On the other hand, at above 36 °C, they decrease in pigmentation, protecting the growth compared to bacteria with temperature‐independent high pigmentation. Integrating the temperature‐responsive circuit into an ELM has the potential to improve living material performance by optimizing growth and protein production in the face of seasonal temperature changes.
3D Neuromorphic Hardware with Single Thin‐Film Transistor Synapses Over Single Thin‐Body Transistor Neurons by Monolithic Vertical Integration
Authors: Han Joon‐Kyu , Lee Jung‐Woo , Kim Yeeun , Kim Young Bin , Yun Seong‐Yun , Lee Sang‐Won , Yu Ji‐Man , Lee Keon Jae , Myung Hyun , Choi Yang‐Kyu
Published: September 2023

Neuromorphic hardware with a spiking neural network (SNN) can significantly enhance the energy efficiency for artificial intelligence (AI) functions owing to its event‐driven and spatiotemporally sparse operations. However, an artificial neuron and synapse based on complex complementary metal‐oxide‐semiconductor (CMOS) circuits limit the scalability and energy efficiency of neuromorphic hardware. In this work, a neuromorphic module is demonstrated composed of synapses over neurons realized by monolithic vertical integration. The synapse at top is a single thin‐film transistor (1TFT‐synapse) made of poly‐crystalline silicon film and the neuron at bottom is another single transistor (1T‐neuron) made of single‐crystalline silicon. Excimer laser annealing (ELA) is applied to activate dopants for the 1TFT‐synapse at the top and rapid thermal annealing (RTA) is applied to do so for the 1T‐neuron at the bottom. Internal electro‐thermal annealing (ETA) via the generation of Joule heat is also used to enhance the endurance of the 1TFT‐synapse without transferring heat to the 1T‐neuron at the bottom. As neuromorphic vision sensing, classification of American Sign Language (ASL) is conducted with the fabricated neuromorphic module. Its classification accuracy on ASL is ≈92.3% even after 204 800 update pulses.
Sufficiently Enriched Dual‐Ion Batteries with Ferrocenyl Substituted Nickel(II) Norcorrole Organic Electrodes
Authors: Zhang Shaoning , Hwang Jinkwang , Phung Quan Manh , Matsumoto Kazuhiko , Hagiwara Rika , Shin Ji‐Young
Published: September 2023

Ferrocenyl‐substituted nickel(II) norcorrole and nickel(II) porphyrin (Fc2NiNc and Fc2NiPor, respectively) are prepared as active electrode materials for dual‐ion batteries, which enables the systematically study of aromaticity and antiaromaticity for organic electrode materials. Intrinsically, Fc2NiNc and Fc2NiPor electrodes have excellent electrochemical behaviors with dual ion interaction with Li cations and bis(fluorosulfonyl)amide [FSA]– inorganic anions from the ionic liquid electrolyte, inducing high capacities (259 mAh g−1 for Fc2NiNc and 200 mAh g−1 for Fc2NiPor). The dominance of pseudocapacitive charge storage is exhibited by the Fc2NiNc and Fc2NiPor electrodes giving rise to rapid charge‐discharge processes. Computational calculation conclusively demonstrates the mechanism of multi‐electron redox reaction resulting in high discharge capacities and aromatic stabilization energy toward achieving a stable long‐term cyclability over 1000 cycles at high current density. Furthermore, Li4Ti5O12/IL/Fc2NiNc cells exhibit high power and energy densities (234 Wh kg−1 at 118 W kg−1) and accomplish outstanding cyclability over 10 000 cycles. This work provides a strategy for designing robust organic electrode materials for dual‐ion batteries.
Educator's blueprint: A how‐to guide on survey administration
Authors: Ogle Kathleen Y. , Hill Jeffery , Santen Sally A. , Gottlieb Michael , Artino Anthony R.
Published: September 2023

In this paper, we take the lessons learned from designing a survey and collecting validity evidence and prepare to administer the survey for research. We focus specifically on how researchers can reach individuals in the target population, methods of contact and engagement, evidence‐informed factors that enhance participation, and recommendations for follow‐up with nonrespondents. We also discuss the challenges of survey administration and provide guidance for navigating low response rates. Surveys are a common tool used to evaluate educational initiatives and collect data for all types of research. However, many clinician educators conducting survey‐based evaluation and research may struggle to efficiently administer their survey. As a result, they often struggle to obtain appropriate response rates and thus may have difficulty publishing their survey results. Previous papers in this series focused on the initial steps of survey development and validation, but it is equally important to understand how best to administer your survey to obtain meaningful responses from a representative sample.
Dynamic aggregation of carbon dots self‐stabilizes symmetry breaking for exceptional hydrogen production with near‐infrared light
Authors: Zhang Qi , Zhang Ya , Shi Hu , Zhang Hongxia , Zhao Jianghong , Zheng Zhanfeng , Yang Hengquan , Yang Pengju
Published: September 2023

Developing new photosystems that integrate broad‐band near‐infrared (NIR) light harvesting and efficient charge separation is a long‐sought goal in the photocatalytic community. In this work, we develop a novel photochemical strategy to prepare light‐active carbon dots (CDs) under room temperature and discover that the aggregation of CDs can broaden the light absorption to the NIR region due to the electronic couplings between neighboring CDs. Importantly, the dynamic non‐covalent interactions within CD aggregates can stabilize symmetry breaking and thus induce large dipole moments for charge separation and transfer. Furthermore, the weak non‐covalent interactions allow for flexible design of the aggregated degrees and the local electronic structures of CD aggregates, further strengthening NIR‐light harvesting and charge separation efficiency. As a result, the CD aggregates achieve a record apparent quantum yield of 13.5% at 800 nm, which is one of the best‐reported values for NIR‐light‐driven hydrogen photosynthesis to date. Moreover, we have prepared a series of different CDs and also observed that these CDs after aggregation all exhibit outstanding NIR‐responsive photocatalytic hydrogen production activity, suggesting the universality of aggregation‐enhanced photocatalysis. This discovery opens a new promising platform for using CD aggregates as efficient light absorbers for solar conversion.
Predictors of milk cortisol in North American women
Authors: Anyim Rachael , Li Shanita , Armstrong Daniel , Spathis Rita , James Gary D. , Little Michael A. , Wander Katherine
Published: September 2023

Objectives

Human milk content varies across mother–child dyads, environments, and populations. Among the hormones in milk is cortisol, a glucocorticoid; its impact on the breastfeeding child is unknown. Milk cortisol may constitute a signal to the child's developing physiology which can shape characteristics (e.g., growth, temperament) to prevailing environmental conditions. This exploratory study evaluated the maternal, breastfeeding, and infant characteristics associated with milk cortisol.

Methods

We evaluated archived milk specimens for cortisol using enzyme immunoassay and employed an information‐theoretic approach to assess associations between milk cortisol and participant characteristics with linear regression modeling. Because we employed secondary data, information for some variables likely to impact milk cortisol variation (e.g., time of day, socioeconomic status, maternal or infant body mass index, milk energy density) was unavailable.

Results

Participants were 48 lactating mothers from upstate New York, aged 21–40 years. Milk cortisol ranged from 0.098 to 1.007 μg/dL. Child age ranged from 1 to 26 months. In linear regression employing best fit modeling criteria, milk cortisol increased with child age (B: 0.069; p: .000; a 7.1% increase in milk cortisol for each month of child age), while child symptoms of illness (B: −0.398; p: .057; a 33% decrease) and consumption of complementary foods (B: −.525; p: .020; a 41% decrease) were associated with lower milk cortisol.

Conclusions

We speculate that increasing milk cortisol with child age plays a role in signaling development (e.g., as increasing independence increases risk for injury and other negative health outcomes), independent of the maternal stressors we could capture.
DFT Mechanistic Insights into the Ni(II)‐Catalyzed Enantioselective Arylative Cyclization of Tethered Allene‐Ketones
Authors: Chao Chi Bong Eric , Pyne Stephen G. , Hyland Christopher J. T. , Lee Richmond
Published: September 2023

Density functional theory (DFT) has provided a detailed mechanistic picture for the redox neutral nickel(II)‐catalyzed arylative cyclization reactions of a tethered allene‐ketone with arylboronic acids. A mechanistic rationale for the high diastereo‐ and enantioselectivity achieved experimentally at high reaction temperature was uncovered through modeling the reaction with a chiral ligand and the predicted stereochemical outcome corroborates with experimental results. An unprecedented mechanism for the base‐free organoboron transmetalation was revealed and the regioselectivity of migratory insertion of tethered allene‐ketones as well as the stability of the possible allylnickel isomers (σ‐allyl vs π‐allyl) were clarified. The multifaceted nature of the reaction is revealed with certain elementary steps preferring cationic compared to the neutral state.
Cancer treatment delays among cancer patients living with HIV during the COVID‐19 pandemic in the United States
Authors: Khouri Ashley , Islam Jessica Y. , Van Bibber Nathan W. , Coghill Anna E. , Suneja Gita
Published: September 2023

Background

The COVID‐19 pandemic led to care disruptions across the cancer continuum. It is unknown if immunosuppressed patients with cancer, who may be at higher risk for complications of SARS‐CoV‐2 infection, are disproportionately impacted. Thus, we aimed to compare delays in cancer treatment initiation between people living with HIV (PLWH) and cancer, the general cancer population (GCP), and patients with cancer and a history of solid organ transplant (SOT). Comparisons were made across the period 2 years preceding the pandemic versus the first year of the pandemic.

Methods

We used data from a real‐world electronic health record‐derived de‐identified database (2018–2021) comprised of US patients with cancer from 800 sites of care across the country. We included patients with 19 different cancer types. We calculated time to cancer treatment initiation (TTI) as the difference between the date of cancer diagnosis and the earliest date that cancer treatment was recorded.

Results

The sample included 181 PLWH, 65,073 GCP patients, and 195 patients with a SOT. Difference‐in‐difference regression models adjusted for age, sex, and presence of metastatic disease at cancer diagnosis revealed a significant increase in delayed TTI among PLWH compared to the GCP during COVID‐19 versus prior to COVID‐19, with delays increasing by approximately 1 month during the pandemic (DID: 32.6 days [8.9–56.3]; p = 0.007). The increase in TTI for PLWH was observed across treatment modalities, including surgery (DID: 55.1 [28.8–81.3], p < 0.001) and systemic therapy (DID: 30.4 [4.6–56.3], p = 0.021).

Conclusions/Relevance

PLWH experienced significant delays in cancer treatment initiation after diagnosis during the first year of COVID‐19, delays that may negatively impact cancer outcomes. These data warrant patient and provider attention as the pandemic continues to impact the US healthcare system.
Piper chaba, an Indian spice plant extract, inhibits cell cycle G1/S phase transition and induces intrinsic apoptotic pathway in luminal breast cancer cells
Authors: Prajapati Kumari Sunita , Kumar Shashank
Published: September 2023

Piper chaba (Piperaceae) is a medicinal spice plant that possesses several pharmacological activities. In the present study, we for the first time studied the effect of P. chaba extract on breast cancer cells. P. chaba stem methanolic (PCSM) extract produced time and dose dependent cytotoxicity in luminal breast cancer cells (MCF‐7 and T47D) with a minimal toxicity in breast normal cells (MCF‐10A) at 10–100 µg/mL concentration. PCSM extract exerts 16.79 and 31.21 µg/mL IC50 for T47D and MCF‐7 cells, respectively, in 48 h treatment. PCSM significantly arrests the T47D cells at the G0/G1 phase by reducing the CCND1 and CDK4 expression at mRNA and protein levels. PCSM extract treatment significantly altered nuclear morphology, mitochondria membrane potential, and production of reactive oxygen species in T47D cells at IC50 concentration. Extract treatment significantly altered the Bax/Bcl‐2 ratio and altered caspase 8 and 3 mRNA/protein levels in T47D cells. Confocal microscopy showed an increase in late apoptosis in PCSM extract‐treated breast cancer cells at IC50. Further, an increased caspase 9 and caspase 3/7 enzymatic activity was observed in test cells compared with nontreated cells. In conclusion, P. chaba phytocompound possesses the potential to induce cell cycle arrest and induce apoptosis in luminal breast cancer cells.
Primary intrapulmonary thymoma a case report
Authors: Wasim Jamal Sheikh Muhammad , Hussein Mousa , Albakri Mutaz , Rasheed Ibrahim , Hameed Mansoor , Ul Haq Irfan , Thomas Merlin , Al Bozom Issam , Abdul Sattar Hisham
Published: September 2023

Primary intrapulmonary thymoma (PIT), defined as the presence of thymoma tissue in the lung without an accompanying mediastinal component, is uncommon and so offers a diagnostic quandary. We describe the case of PIT in an 81‐year‐old man.
Duplication errors due to brand name confusion; It is not always the name—Short case series
Authors: Mamunuwa N. , Jayamanne S. , Wijekoon N. , Coombes J. , Perera D. , Shanika T. , Mohamed F. , Lynch C. , De Silva A. , Dawson A.
Published: September 2023

Key Clinical Message

Confusion of drug names has been identified as a leading cause of medication errors and potential iatrogenic harm. Most of these errors occur because of look‐alike or sound‐alike drugs. This case series gives examples of duplication errors due to brand confusion, where there are no similarities in the names.
Cysteine‐Cysteine Cross‐Conjugation of both Peptides and Proteins with a Bifunctional Hypervalent Iodine‐Electrophilic Reagent
Authors: Koutsopetras Ilias , Mishra Abhaya Kumar , Benazza Rania , Hernandez‐Alba Oscar , Cianférani Sarah , Chaubet Guilhem , Nicolai Stefano , Waser Jérôme
Published: September 2023

Peptide and protein bioconjugation sees ever‐growing applications in the pharmaceutical sector. Novel strategies and reagents that can address the chemo‐ and regioselectivity issues inherent to these biomolecules, while delivering stable and functionalizable conjugates, are therefore needed. Herein, we introduce the crosslinking ethynylbenziodazolone (EBZ) reagent JW‐AM‐005 for the conjugation of peptides and proteins through the selective linkage of cysteine residues. This easily accessed compound gives access to peptide dimers or stapled peptides under mild and tuneable conditions. Applied to the antibody fragment of antigen binding (Fab) species, JW‐AM‐005 delivered rebridged proteins in a one‐pot three‐reaction process with high regioselectivity, outperforming the standard reagents commonly used for this transformation.
Identification of in situ Generated Iron‐Vacancy Induced Oxygen Evolution Reaction Kinetics on Cobalt Iron Oxyhydroxide†
Authors: Yao Na , Zhu Juan , Jia Hongnan , Cong Hengjiang , Luo Wei
Published: September 2023

Comprehensive Summary

Developing highly efficient and low‐cost electrocatalysts towards oxygen evolution reaction (OER) is essential for practical application in water electrolyzers and rechargeable metal‐air batteries. Although Fe‐based oxyhydroxides are regarded as state‐of‐the‐art non‐noble OER electrocatalysts, the origin of performance enhancement derived from Fe doping remains a hot topic of considerable discussion. Herein, we demonstrate that in situ generated Fe vacancies in the pristine CoFeOOH catalyst through a pre‐conversion process during alkaline OER result from dynamic Fe dissolution, identifying the origin of Fe‐vacancy‐induced enhanced OER kinetics. Density functional theory (DFT) calculations and experimental results including X‐ray absorption fine‐structure spectroscopy, in situ UV‐Vis spectroscopy, and in situ Raman spectroscopy reveal that the Fe vacancies could significantly promote the d‐band center and valence states of adjacent Co sites, alter the active site from Fe atom to Co atom, accelerate the formation of high‐valent active Co4+ species, and reduce the energy barrier of the potential‐determining step, thereby contribute to the significantly enhanced OER performance.
Logarithmic cotangent bundles, Chern‐Mather classes, and the Huh‐Sturmfels involution conjecture
Authors: Maxim Laurenţiu G. , Rodriguez Jose Israel , Wang Botong , Wu Lei
Published: September 2023

Using compactifications in the logarithmic cotangent bundle, we obtain a formula for the Chern classes of the pushforward of Lagrangian cycles under an open embedding with normal crossing complement. This generalizes earlier results of Aluffi and Wu‐Zhou. The first application of our formula is a geometric description of Chern‐Mather classes of an arbitrary very affine variety, generalizing earlier results of Huh which held under the smooth and schön assumptions. As the second application, we prove an involution formula relating sectional maximum likelihood (ML) degrees and ML bidegrees, which was conjectured by Huh and Sturmfels in 2013.
Artificial intelligence revolutionizing drug development: Exploring opportunities and challenges
Authors: Tiwari Prafulla C. , Pal Rishi , Chaudhary Manju J. , Nath Rajendra
Published: September 2023

By harnessing artificial intelligence (AI) algorithms and machine learning techniques, the entire drug discovery process stands to undergo a profound transformation, offering a myriad of advantages. Foremost among these is the ability of AI to conduct swift and efficient screenings of expansive compound libraries, significantly augmenting the identification of potential drug candidates. Moreover, AI algorithms can prove instrumental in predicting the efficacy and safety profiles of candidate compounds, thus endowing invaluable insights and reducing reliance on extensive preclinical and clinical testing. This predictive capacity of AI has the potential to streamline the drug development pipeline and enhance the success rate of clinical trials, ultimately resulting in the emergence of more efficacious and safer therapeutic agents. However, the deployment of AI in drug discovery introduces certain challenges that warrant attention. A primary hurdle entails the imperative acquisition of high‐quality and diverse data. Furthermore, ensuring the interpretability of AI models assumes critical importance in securing regulatory endorsement and cultivating trust within scientific and medical communities. Addressing ethical considerations, including data privacy and mitigating bias, represents an additional momentous challenge, requiring assiduous navigation. In this review, we provide an intricate and comprehensive overview of the multifaceted challenges intrinsic to conventional drug development paradigms, while simultaneously interrogating the efficacy of AI in effectively surmounting these formidable obstacles.
Network and parasitological analyses reveal latitudinal gradient in bats‐ectoparasitic fly interactions across the Neotropic
Authors: Biz Luana S. , Bastazini Vinicius A. G. , Carvalho Fernando , Ramos Pereira Maria João
Published: September 2023

Ecological interactions between parasites and their hosts play a fundamental role in evolutionary processes. Selection pressures are exerted on parasites and their hosts, usually resulting in high levels of specificity. Such is the case of ectoparasitic bat‐flies, but how large‐scale spatial gradients affect the dynamics of their interactions with their bat hosts is still unknown. In the present study, we investigated interaction patterns between bats and their ectoparasitic flies (Streblidae and Nycteribiidae), both presenting their peak of diversity in the Neotropical region, along a latitudinal gradient. Using network analyses and parasitic indices, grounded on the latitudinal diversity gradient pattern, we evaluated how spatial gradients affect species interactions and parasitic indices at the biogeopraphic scale, with increasing species richness in interaction networks closer to the tropics, leading to increases in network modularity, size, and specialization, and to a decrease in nesting and connectivity. We conducted a literature review, focusing on studies done in the Neotropical region, and own data. We obtained a bat richness of 97 species parasitized by 128 species of ectoparasitic flies, distributed into 57 interaction networks between latitudes 29° S and 19° N in the Neotropic. Network metrics and parasitic indices varied along the latitudinal gradient, with changes in the richness of bats and their ectoparasitic flies and in the structure of their interactions; network specialization, modularity, and connectance increase with latitude, while network size decreases with latitude. Regions closer to the equator had higher parasite loads. Our results show that interaction network metrics present a latitudinal gradient and that such interactions, when observed at a local scale, hide variations that only become perceptible at larger scales. In this way, ectoparasites such as bat flies are not only influenced by the ecology and biology of their hosts, but also by other environmental factors acting directly on their distribution and survival.
Practical algorithms for early diagnosis of heart failure and heart stress using NT‐proBNP: A clinical consensus statement from the Heart Failure Association of the ESC
Authors: Bayes‐Genis Antoni , Docherty Kieran F. , Petrie Mark C. , Januzzi James L. , Mueller Christian , Anderson Lisa , Bozkurt Biykem , Butler Javed , Chioncel Ovidiu , Cleland John G.F. , Christodorescu Ruxandra , Del Prato Stefano , Gustafsson Finn , Lam Carolyn S.P. , Moura Brenda , Pop‐Busui Rodica , Seferovic Petar , Volterrani Maurizio , Vaduganathan Muthiah , Metra Marco , Rosano Giuseppe
Published: September 2023

Diagnosing heart failure is often difficult due to the non‐specific nature of symptoms, which can be caused by a range of medical conditions. Natriuretic peptides (NPs) have been recognized as important biomarkers for diagnosing heart failure. This document from the Heart Failure Association examines the practical uses of N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) in various clinical scenarios. The concentrations of NT‐proBNP vary according to the patient profile and the clinical scenario, therefore values should be interpreted with caution to ensure appropriate diagnosis. Validated cut‐points are provided to rule in or rule out acute heart failure in the emergency department and to diagnose de novo heart failure in the outpatient setting. We also coin the concept of ‘heart stress’ when NT‐proBNP levels are elevated in an asymptomatic patient with risk factors for heart failure (i.e. diabetes, hypertension, coronary artery disease), underlying the development of cardiac dysfunction and further increased risk. We propose a simple acronym for healthcare professionals and patients, FIND‐HF, which serves as a prompt to consider heart failure: Fatigue, Increased water accumulation, Natriuretic peptide testing, and Dyspnoea. Use of this acronym would enable the early diagnosis of heart failure. Overall, understanding and utilizing NT‐proBNP levels will lead to earlier and more accurate diagnoses of heart failure ultimately improving patient outcomes and reducing healthcare costs.
An in vitro model for osteoarthritis using long‐cultured inflammatory human macrophages repeatedly stimulated with TLR agonists
Authors: Ummarino Aldo , Pensado‐López Alba , Migliore Roberta , Alcaide‐Ruggiero Lourdes , Calà Nicholas , Caputo Michele , Gambaro Francesco M. , Anfray Clément , Ronzoni Flavio L. , Kon Elizaveta , Allavena Paola , Torres Andón Fernando
Published: September 2023

Osteoarthritis (OA) is characterized by an abundance of inflammatory M1‐like macrophages damaging local tissues. The search for new potential drugs for OA suffers from the lack of appropriate methods of long‐lasting inflammation. Here we developed and characterized an in vitro protocol of long‐lasting culture of primary human monocyte‐derived macrophages differentiated with a combination of M‐CSF+GM‐CSF that optimally supported long‐cultured macrophages (LC‐Mϕs) for up to 15 days, unlike their single use. Macrophages repeatedly stimulated for 15 days with the TLR2 ligand Pam3CSK4 (LCS‐Mϕs), showed sustained levels over time of IL‐6, CCL2, and CXCL8, inflammatory mediators that were also detected in the synovial fluids of OA patients. Furthermore, macrophages isolated from the synovia of two OA patients showed an expression profile of inflammation‐related genes similar to that of LCS‐Mϕs, validating our protocol as a model of chronically activated inflammatory macrophages. Next, to confirm that these LCS‐Mϕs could be modulated by anti‐inflammatory compounds, we employed dexamethasone and/or celecoxib, two drugs widely used in OA treatment, that significantly inhibited the production of inflammatory mediators. This easy‐to‐use in vitro protocol of long‐lasting inflammation with primary human macrophages could be useful for the screening of new compounds to improve the therapy of inflammatory disorders.
Novel method of isolating nuclei of human oligodendrocyte precursor cells reveals substantial developmental changes in gene expression and H3K27ac histone modification
Authors: Kozlenkov Alexey , Vadukapuram Ramu , Zhou Ping , Fam Peter , Wegner Michael , Dracheva Stella
Published: September 2023

Oligodendrocyte precursor cells (OPCs) generate differentiated mature oligodendrocytes (MOs) during development. In adult brain, OPCs replenish MOs in adaptive plasticity, neurodegenerative disorders, and after trauma. The ability of OPCs to differentiate to MOs decreases with age and is compromised in disease. Here we explored the cell specific and age‐dependent differences in gene expression and H3K27ac histone mark in these two cell types. H3K27ac is indicative of active promoters and enhancers. We developed a novel flow‐cytometry‐based approach to isolate OPC and MO nuclei from human postmortem brain and profiled gene expression and H3K27ac in adult and infant OPCs and MOs genome‐wide. In adult brain, we detected extensive H3K27ac differences between the two cell types with high concordance between gene expression and epigenetic changes. Notably, the expression of genes that distinguish MOs from OPCs appears to be under a strong regulatory control by the H3K27ac modification in MOs but not in OPCs. Comparison of gene expression and H3K27ac between infants and adults uncovered numerous developmental changes in each cell type, which were linked to several biological processes, including cell proliferation and glutamate signaling. A striking example was a subset of histone genes that were highly active in infant samples but fully lost activity in adult brain. Our findings demonstrate a considerable rearrangement of the H3K27ac landscape that occurs during the differentiation of OPCs to MOs and during postnatal development of these cell types, which aligned with changes in gene expression. The uncovered regulatory changes justify further in‐depth epigenetic studies of OPCs and MOs in development and disease.
Impact of sample size and regression of tissue‐specific signals on effective connectivity within the core default mode network
Authors: Silchenko Alexander N. , Hoffstaedter Felix , Eickhoff Simon B.
Published: September 2023

Interactions within brain networks are inherently directional, which are inaccessible to classical functional connectivity estimates from resting‐state functional magnetic resonance imaging (fMRI) but can be detected using spectral dynamic causal modeling (DCM). The sample size and unavoidable presence of nuisance signals during fMRI measurement are the two important factors influencing the stability of group estimates of connectivity parameters. However, most recent studies exploring effective connectivity (EC) have been conducted with small sample sizes and minimally pre‐processed datasets. We explore the impact of these two factors by analyzing clean resting‐state fMRI data from 330 unrelated subjects from the Human Connectome Project database. We demonstrate that both the stability of the model selection procedures and the inference of connectivity parameters are highly dependent on the sample size. The minimum sample size required for stable DCM is approximately 50, which may explain the variability of the DCM results reported so far. We reveal a stable pattern of EC within the core default mode network computed for large sample sizes and demonstrate that the use of subject‐specific thresholded whole‐brain masks for tissue‐specific signals regression enhances the detection of weak connections.
Thymocyte selection‐associated high mobility box protein regulates T lymphocytes exhaustion in patients with myelodysplastic syndromes by inhibiting PI3K/AKT/mTOR pathway
Authors: Niu Haiyue , Zhang Mengying , Liu Mengyuan , Yang Liyan , Yang Liping , Ren Jie , Yu Yating , Liu Yumei , Xing Limin , Shao Zonghong , Wang Huaquan
Published: September 2023

Myelodysplastic syndromes (MDS) patients often experience CD8+T lymphocytes exhaustion, which plays a crucial role in the development of MDS. However, the specific role of thymocyte selection‐associated high mobility box protein (TOX) in the CD8+T lymphocytes exhaustion in MDS patients remains unclear. In this study, we investigated the role of TOX in CD8+T lymphocytes exhaustion in patients with MDS. The expression of TOX, inhibitory receptors (IRs), and functional molecules in peripheral blood T lymphocytes of MDS patients and normal controls were detected using flow cytometry. Lentiviral transduction was used to create stable TOX‐knockdown CD8+T lymphocytes, and small interfering RNA (si‐RNA) was used to knock down TOX in Jurkat cells. The expression of TOX was found to be significantly higher in CD8+T lymphocytes of MDS patients compared to normal controls. This was associated with upregulated IRs and reduced expression of functional molecules such as Granzyme and Perforin. Myelodysplastic syndromes patients with higher TOX expression had poor clinical indicators and shorter survival. Knockdown of TOX using sh‐RNA partially reverses the exhausted phenotype and enhances the lethality of CD8+T lymphocytes. Moreover, the knockdown of TOX using si‐RNA in Jurkat cells improved cell proliferation activity, down‐regulated IRs and activated PI3K/AKT/mTOR signaling pathway. TOX promotes the exhaustion of CD8+T lymphocytes by inhibiting PI3K/AKT/mTOR pathway, and targeted inhibition of TOX could partially restore the effector functions and activity of CD8+T lymphocytes.
Efficacy and acceptability of adjunctive n‐acetylcysteine for psychotic disorders: Systematic review and meta‐analysis
Authors: Zhang Qun , Liu Ziping , Wang Ting , Yu Min , Li Xiaoqian
Published: September 2023

Introduction

N‐acetylcysteine (NAC) augmentation of antipsychotic medication has been studied in psychotic disorders but the results are inconsistent. This meta‐analysis aimed to evaluate the efficacy and acceptability of NAC as an augmentation strategy for psychotic disorders.

Methods

PubMed, Web of Science, EMBASE, PsycINFO, Cochrane Library, and ClinicalTrials.gov were searched until the date of November 28, 2022. The inclusion criteria were randomized controlled trials (RCTs) comparing NAC and placebo in patients with psychotic disorders. The outcomes were the psychotic symptoms measured by the Positive and Negative Syndrome Scale (PANSS) and drop‐out rates.

Results

A total of 594 patients from eight trials were included. The results showed that no difference was found in score changes of PANSS total, positive, negative, or general psychopathology scale scores between the NAC group and placebo group in both time points (≤24 weeks and >24 weeks). There was also no statistical difference in drop‐out rates between the two groups.

Conclusion

For the moment, it is not appropriate to recommend NAC as an augmentation of antipsychotic medication to treat psychotic disorders in routine clinical practice.
SAtUNet: Series atrous convolution enhanced U‐Net for lung nodule segmentation
Authors: Selvadass Salomi , Bruntha P. Malin , Sagayam K. Martin , Günerhan Hatıra
Published: September 2023

Precise and unambiguous segmentation of pulmonary nodules from the CT images is imperative for a CAD framework implementation delineated for the prognosis of lung cancer. Lung nodule segmentation is an appealing research discipline for accurate dismemberment of lung cancer but the irregularity in shades, contours, and compositions, and the affinity between the tumors and the neighboring regions makes it an arduous task. This paper proffers a series atrous convolution enhanced U‐Net which uses a series of concatenated dilated convolution blocks after every stage in the encoder and decoder path. Our approach helps in obtaining the quintessential components from the feature maps, in addition to the absolute convergence of the model. It is largely assessed on the publicly accessible LIDC‐IDRI dataset. The average Dice Similarity Coefficient (DSC) obtained is 81.10% with an Intersection over Union (IoU/ Jaccard Index) of 72.24%. Exploratory outcomes prove that our architecture achieves ameliorate performance.
Application of a Low Cost Ceramic Filter to a Membrane Bioreactor for Greywater Treatment
Authors: Hasan Md. Mahmudul , Shafiquzzaman Md , Nakajima Jun , Ahmed Abdel Kader T. , Azam Mohammad Shafiul
Published: September 2023

The performance of a low cost and simple ceramic filter to a membrane bioreactor (MBR) process was evaluated for greywater treatment. The ceramic filter was submerged in an acrylic cylindrical column bioreactor. Synthetic greywater (prepared by shampoo, dish cleaner and laundry detergent) was fed continuously into the reactor. The filter effluent was obtained by gravitational pressure. The average flux performance was observed to be 11.5 LMH with an average hydraulic retention time of 1.7 days. Complete biodegradation of surfactant (methylene blue active substance removal: 99–100%) as well as high organic removal performance (biochemical oxygen demand: 97–100% and total organic carbon: >88%) was obtained. The consistency of flux (11.5 LMH) indicated that the filter can be operated for a long time without fouling. The application of this simple ceramic filter would make MBR technology cost‐effective in developing countries for greywater reclamation and reuse.
Bioactivity of selenium‐containing pyridinium salts: Prospecting future pharmaceutical constituents to treat liver diseases involving oxidative stress
Authors: Castro Ediandra T. , Alves Amália G. , de Bittencourt Maia Daniela , Magalhães Larissa S. , Paim Mariana P. , Penteado Filipe , Gomes Caroline S. , Lenardão Eder J. , Brüning César A. , Bortolatto Cristiani F.
Published: September 2023

Redox imbalance leads to oxidative stress that causes irreversible cellular damage. The incorporation of the antioxidant element selenium (Se) in the structure of pyridinium salts has been used as a strategy in chemical synthesis and can be useful in drug development. We investigated the antioxidant activity of Se‐containing pyridinium salts (named Compounds 3A, 3B, and 3C) through in vitro tests. We focused our study on liver protein carbonylation, liver lipoperoxidation, free radical scavenging activity (1,1‐diphenyl‐2‐picryl‐hydrazil [DPPH]; 2,2′‐azinobis(3‐ethylbenzothiazoline‐6‐sulfonic acid [ABTS]), and enzyme‐mimetic activity assays (glutathione S‐transferase [GST]‐like; superoxide dismutase [SOD]‐like). In addition, 2‐(4‐chlorophenyl)‐2‐oxoethyl)‐2‐((phenylselanyl)methyl)pyridin‐1‐ium bromide (3C) was selected to evaluate the acute oral toxicity in mice due to the best antioxidant profile. The three compounds were effective in reducing the levels of protein carbonylation and lipoperoxidation in the liver in a µM concentration range. All compounds demonstrated scavenger activity of DPPH and ABTS radicals, and GST‐like action. No significant effects were detected in the SOD‐like assay. Experimental data also showed that the acute oral treatment of mice with Compound 3C (50 and 300 mg/kg) did not cause mortality or change markers of liver and kidney functions. In summary, our findings reveal the antioxidant potential of Se‐containing pyridinium salts in liver tissue, which could be related to their radical scavenging ability and mimetic action on the GST enzyme. They also demonstrate a low toxicity potential for Compound 3C. Together, the promising results open space for future studies on the therapeutic application of these molecules.
A survey on utilization and barriers of digital removable prostheses in the US dental education
Authors: Elkassaby Heba , Touloumi Foteini , Clark Wendy Auclair , Jiang Shuying , Mahrous Ahmed , Mainelli Julia , Moghadam Marjan , Zemnick Candice , Sadid‐Zadeh Ramtin
Published: September 2023

Purpose

Gaining knowledge on the extent of digital technology implementation in dental education and the barriers to it will help inform future directions to promote the use of such technology and will enhance dental education. This study aimed to investigate the utilization of digitally fabricated removable prostheses and the potential obstacles to implementing such technology in US dental schools.

Methods

A survey was developed and distributed to the restorative dentistry department chairs and postdoctoral prosthodontic program directors. The survey delivery protocol included follow‐up emails 1 week, 3 weeks, and 4 weeks after the initial email. The collected data were analyzed descriptively.

Results

The response rate was 85% and 45% for predoctoral and postdoctoral prosthodontic programs, respectively. The results showed that 88.06% of the predoctoral programs and 95.65% of the postdoctoral prosthodontic programs implement digital complete dentures in the curriculum; however, the digital removable partial dentures implementation rate was recorded at 70.77% in predoctoral programs and 61.9% in postdoctoral prosthodontic programs.

Conclusions

Dental schools are challenged by cost, design software limitations, IT and laboratory support, and faculty training. Multifaceted support is instrumental in further implementing digital removable prosthodontics into dental education.
Photovoice: Visualizing the engineering identity experiences of sophomore students
Authors: Henderson Jerrod A. , McGowan Brian L. , Wawire Joan , Benjamin Le Shorn S. , Schaefer Kristin L. , Alarcón Jeannette D.
Published: September 2023

Background

Researchers have shown that students leave undergraduate engineering programs during the first 2 years. Justifiably, many studies have tried to tackle engineering student persistence and attrition, especially during the first year, and then developed interventions to address the challenges. Although those interventions have improved freshmen retention in some institutions, less has been published on the impacts of these interventions on the sophomore student experience.

Purpose

To contribute to the knowledge base about all engineering students, we examined the experiences of sophomore engineering students and explored how these experiences might be related to their identities as engineers.

Design/Method

We conducted this study using photovoice, a methodology in which participants submit photographs to describe their experiences and give recommendations on improving their experiences and resolving their concerns. Participants submitted three sets of pictures (at the beginning, middle, and end of the semester) and participated in focus groups to aid in illuminating their experiences. We analyzed data using thematic analysis.

Results

We inductively determined three themes: on the frame, out of focus, and prefigures. These themes illustrate the experiences of sophomore engineering students, enabling us to see what interest, competence, and recognition as engineers looked like from their perspectives.

Conclusions

Participants grappled with the tension between their personal, social, and engineering identities. Photovoice empowered them to author and illustrate that they could exist beyond the murky middle.
A challenging case of cutaneous leishmaniasis with thrombophlebitic complication
Authors: Willemart Antoine , Mengeot Laura , Yombi Jean‐Cyr , Secco Léo Paul , Baeck Marie
Published: September 2023

We report a case of cutaneous leishmaniasis caused by Leishmania guyanensis with sporotrichoid lymphocutaneous dissemination of the parasite and thrombophlebitic complication in a 32‐year‐old man who had recently travelled to French Guiana. After initial failure of empirical treatment with amphotericin B, the patient evolved favourably on high doses of intramuscular injections of meglumine antimoniate for 2 months. This case illustrates the existence of lymphocutaneous forms and possible thrombophlebitic complications of leishmaniasis. It also highlights the challenges in the management of leishmaniasis, despite the existence of guidelines and a wide therapeutic arsenal.
Controlled Radical Polymerization Initiated by Solvated Electrons
Authors: Li Xun , Pan Zhaoyan , Xia Yichen , Rui Jiayu , Zhu Meng , Ren He , Huang Jian
Published: September 2023

Solvated electron (esol−) is highly reducing species and apt to initiate monomers via one‐electron transfer reaction. Herein, utilizing the esol− solution of Na/hexamethylphosphoramide, radical and anionic initiations are observed respectively, which heavily depend on Na concentrations. Interestingly, this initiation system, in states of lower Na concentrations, higher molar conductivities and less paired esol−, give rise to a controlled radical polymerization (CRP) to yield polymers with predictable molecular weights and narrow molecular weight distributions (the lowest Ð = 1.25). This CRP presents unique behaviors, like solvent effect, electric field effect, and unusual copolymerization phenomenon. A semi‐conjugated radical carrying a negative charge is proposed to be responsible for the CRP. This system gives a distinct way to regulate CRP from current CRPs, and offers new insights into the monomer initiation by esol−.