bluuebunny/crossref_metadata_2025 huggingface dataset:
Neonatal Intensive Care Unit Resource Use for Infants at 22 Weeks’ Gestation in the US, 2008-2021
Authors: Rysavy Matthew A. , Bennett Monica M. , Ahmad Kaashif A. , Patel Ravi M. , Shah Zubin S. , Ellsbury Dan L. , Clark Reese H. , Tolia Veeral N.
Published: February 2024

Importance

During the past decade, clinical guidance about the provision of intensive care for infants born at 22 weeks’ gestation has changed. The impact of these changes on neonatal intensive care unit (NICU) resource utilization is unknown.

Objective

To characterize recent trends in NICU resource utilization for infants born at 22 weeks’ gestation compared with other extremely preterm infants (≤28 weeks’ gestation) and other NICU-admitted infants.

Design, Setting, and Participants

This is a serial cross-sectional study of 137 continuously participating NICUs in 29 US states from January 1, 2008, through December 31, 2021. Participants included infants admitted to the NICU. Data analysis was performed from October 2022 to August 2023.

Exposures

Year and gestational age at birth.

Main Outcomes and Measures

Measures of resource utilization included NICU admissions, NICU bed-days, and ventilator-days.

Results

Of 825 112 infants admitted from 2008 to 2021, 60 944 were extremely preterm and 872 (466 [53.4%] male; 18 [2.1%] Asian; 318 [36.5%] Black non-Hispanic; 218 [25.0%] Hispanic; 232 [26.6%] White non-Hispanic; 86 [9.8%] other or unknown) were born at 22 weeks’ gestation. NICU admissions at 22 weeks’ gestation increased by 388%, from 5.7 per 1000 extremely preterm admissions in 2008 to 2009 to 27.8 per 1000 extremely preterm admissions in 2020 to 2021. The number of NICU admissions remained stable before the publication of updated clinical guidance in 2014 to 2016 and substantially increased thereafter. During the study period, bed-days for infants born at 22 weeks increased by 732%, from 2.5 per 1000 to 20.8 per 1000 extremely preterm NICU bed-days; ventilator-days increased by 946%, from 5.0 per 1000 to 52.3 per 1000 extremely preterm ventilator-days. The proportion of NICUs admitting infants born at 22 weeks increased from 22.6% to 45.3%. Increases in NICU resource utilization during the period were also observed for infants born at less than 22 and at 23 weeks but not for other gestational ages. In 2020 to 2021, infants born at less than or equal to 23 weeks’ gestation comprised 1 in 117 NICU admissions, 1 in 34 of all NICU bed-days, and 1 in 6 of all ventilator-days.

Conclusions and Relevance

In this serial cross-sectional study of 137 US NICUs from 2008 to 2021, an increasing share of resources in US NICUs was allocated to infants born at 22 weeks’ gestation, corresponding with changes in national clinical guidance.
Prioritizing Maternal Mental Health in Addressing Morbidity and Mortality
Authors: Wisner Katherine L. , Murphy Caitlin , Thomas Megan M.
Published: February 2024

Importance

The rate of maternal mortality in the United States is 2-fold to 3-fold greater than that in other high-income countries. While many national initiatives have been developed to combat maternal mortality, these efforts often fail to include mental illness.

Objective

To highlight the underrecognized contribution of mental illness to maternal mortality, which is nearly double that of postpartum hemorrhage.

Evidence Review

A topic outline was developed to include challenges in measuring perinatal mental conditions and mortality rates; contributions of social determinants of health to mental conditions and mortality; perinatal psychiatric disorder characterization; mechanisms by which maternal mental illness increases mortality, specifically, suicide and addictive disorders; access limitations and care “deserts”; prenatal stress and its impact on reproductive outcomes; increasing clinician expertise through cross-disciplinary education; intervention sites and models; and asserting that mental health is fundamental to maternal health. Publications in the last 3 years were prioritized, particularly those relating to policy. References were selected through consensus. Sources were PubMed, Ovid, direct data published on government websites, and health policy sources such as the Policy Center for Maternal Mental Health.

Findings

Priority was given to recent sources. Citations from 2022-2023 numbered 26; within the last 5 years, 14; and historical references, 15. Recommendations to address each topic area serve as concluding statements for each section. To mitigate the contributions of mental illness to the maternal mortality risk, a coordinated effort is required across professional and governmental organizations.

Conclusions and Relevance

Concrete programmatic and policy changes are needed to reduce perinatal stress and address trauma, standardize the collection of social determinant of health data among perinatal patients, increase access to reproductive psychiatry curricula among prescribers, reduce perinatal mental health and obstetrical deserts, institute paid parental leave, and support seamless integration of perinatal and behavioral health care. Moreover, instead of focusing on a relatively minor portion of the contributors to health that current medical practice targets, fortifying the social foundation strengthens the prospects for the health of families for our current and future generations.
Plasmonic Au3Cu Ordered Nanocrystals Induced Phase Transformation in 2D‐MoS2 for Efficient Hydrogen Evolution
Authors: Qamar Ummiya , Roy Sayak , Kumar Sooraj , Mukherjee Bratindranath , Devi Assa Aravindh Sasikala , Goswami Ankur , Maiti Pralay , Das Santanu
Published: February 2024

The synthesis of ordered gold‐copper (Au3Cu) alloy nanocrystals (≈10 nm) is reported and used in the semiconductor (2H) to metallic (1T) phase transformation of an atomically thin large‐area 2D‐MoS2 grown via CVD technique. The ordered Au3Cu nanocrystals are dispersed over 2D‐MoS2, and the phase transformation is confirmed via Raman spectroscopy followed by X‐ray photoelectron spectroscopy (XPS), while the surface properties of the Au3Cu/2D‐MoS2 is determined by the XPS valence band analysis and ultra‐violet photoemission spectroscopy (UPS). By comparing overpotential and Tafel slopes for Hydrogen Evolution Reaction (HER), a decrease is observed in overpotential by 83.2 mV and Tafel slope by ≈58.25 mV per decade for Au3Cu/MoS2 on light irradiation. This electrocatalytic enhancement of Au3Cu/MoS2 refers to the transformation of semiconducting 2D‐MoS2 to metallic phase under light illumination, thereby altering the surface electronic structures, improving carrier concentrations, lowering the valence band edge, and lowering the free energy of H* adsorption/desorption. Density functional theory (DFT) calculations, along with other surface characterizations, further illustrate that the ordered nanocrystal‐induced phase transformation in 2D‐MoS2 leads to a more durable metallic characteristic, thus, enhancing the surface electrical conductivity, reducing surface potential and Gibbs free energy, and improving the kinetics of photoelectrocatalytic performance of the hybrid structure.
Two Better Than One: Enhanced Photo‐Assisted Li‐O2 Batteries with Bimetallic Fe‐UiO‐66 Metal‐Organic Framework Photocathodes
Authors: Yang Yuting , Hu Xu , Wang Guofan , Han Jiale , Zhang Qinming , Liu Weiwei , Xie Zhaojun , Zhou Zhen
Published: February 2024

Li‐O2 batteries, known for their impressive theoretical specific energy, face significant practical challenges, including slow kinetics, voltage hysteresis, and reduced cycle life. In this study, a novel approach is introduced utilizing a bimetallic metal‐organic framework known as Fe‐UiO‐66 as a multifunctional photocatalyst to enhance the oxygen‐related reactions in photo‐assisted Li‐O2 batteries. In contrast to UiO‐66, Fe‐UiO‐66 exhibits an extended response to visible light, as confirmed through UV–vis and photoluminescence spectra. Electron paramagnetic resonance analysis provides further validation of the pivotal role played by O2− radicals in the electrochemical processes. Additionally, computations are employed to elucidate the distinct function of Fe centers and the underlying reaction mechanisms. Li‐O2 batteries with Fe‐UiO‐66 cathodes have a reduced charge/discharge voltage difference of 0.14 V under illumination and operate stably for 500 cycles. This work encourages MOF‐based photocathode development for Li‐O2 batteries.
A Cu3BHT‐Graphene van der Waals Heterostructure with Strong Interlayer Coupling for Highly Efficient Photoinduced Charge Separation
Authors: Wang Zhiyong , Fu Shuai , Zhang Wenjie , Liang Baokun , Liu Tsai‐Jung , Hambsch Mike , Pöhls Jonas F. , Wu Yufeng , Zhang Jianjun , Lan Tianshu , Li Xiaodong , Qi Haoyuan , Polozij Miroslav , Mannsfeld Stefan C. B. , Kaiser Ute , Bonn Mischa , Weitz R. Thomas , Heine Thomas , Parkin Stuart S. P. , Wang Hai I. , Dong Renhao , Feng Xinliang
Published: February 2024

Two‐dimensional van der Waals heterostructures (2D vdWhs) are of significant interest due to their intriguing physical properties critically defined by the constituent monolayers and their interlayer coupling. Synthetic access to 2D vdWhs based on chemically tunable monolayer organic 2D materials remains challenging. Herein, the fabrication of a novel organic–inorganic bilayer vdWh by combining π‐conjugated 2D coordination polymer (2DCP, i.e., Cu3BHT, BHT = benzenehexathiol) with graphene is reported. Monolayer Cu3BHT with detectable µm2‐scale uniformity and atomic flatness is synthesized using on‐water surface chemistry. A combination of diffraction and imaging techniques enables the determination of the crystal structure of monolayer Cu3BHT with atomic precision. Leveraging the strong interlayer coupling, Cu3BHT‐graphene vdWh exhibits highly efficient photoinduced interlayer charge separation with a net electron transfer efficiency of up to 34% from Cu3BHT to graphene, superior to those of reported bilayer 2D vdWhs and molecular‐graphene vdWhs. This study unveils the potential for developing novel 2DCP‐based vdWhs with intriguing physical properties.
Recent Advances in Multi‐Scale Piezoresistive Interfaces for MXene‐Based Flexible Sensors
Authors: Ge Chengqi , Sun Beibei , Huang Yanhui , Alahi Md. Eshrat E. , Ma Qian , Wei Song , Hui Yun , Huang Zhaoling , Zeng Qi
Published: February 2024

Flexible piezoresistive sensors hold great promise in biomedicine and personal motion detection, attracting significant attention from researchers. Particularly, two‐dimensional (2D) MXene has made remarkable strides in biomedicine, electromagnetic shielding, and other practical applications, due to its exceptional hydrophilicity, biocompatibility, mechanical properties, surface functional groups, and large specific surface area. The ease of composite material formation further makes it ideal for high‐sensitivity flexible sensors. This paper summarizes the principal structural configurations for the multi‐scale interfaces, performance assessment metrics, and the corresponding sensing mechanisms of flexible piezoresistive sensors. Subsequently, the main characteristics and synthesis methods of MXene, especially the related applications and parameters are introduced in detail. The research trends and typical applications of MXene‐based flexible piezoresistive sensors focused on film structures, fiber structures, 3D structures, and hydrogel structures, are highlighted systematically. In addition, the challenges and prospects that promoting the advancement of MXene‐based flexible piezoresistive sensors in future are also discussed, which will revolutionize the sensing field and offer a wealth of opportunities in biomedicine and beyond.
Strong Circularly Polarized Phosphorescence of Achiral Pt(II) Metallomesogen Induced by Using a Chiral Co‐Assembly Strategy
Authors: Li Qihuan , Zou Guo , Li Dong , Liu Chao , Gao Wentong , Li Yang , Cheng Yixiang
Published: February 2024

The high planarity and heavy‐atom effect of Pt(II) metallomesogens promote their stacking in the aggregated state and highly efficient phosphorescence. This makes them promising candidate materials for circularly polarized phosphorescence (CPP) triggered by using a chiral co‐assembly strategy. In this paper, a nematic phase, achiral robot‐like Pt(II) metallomesogen (TFPt) is synthesized, which combines two anchored chiral binaphthyl inducers (R/S1 or R/S2) to construct cholesteric liquid crystal (N*‐LC) co‐assemblies (R/S1)n‐(TFPt)1‐n and (R/S2)n‐(TFPt)1‐n via intermolecular interactions. The resultant N*‐LC chiral co‐assemblies (R1)0.03‐(TFPt)0.97 and (R2)0.03‐(TFPt)0.97 exhibit the strongest CPP emission with high dissymmetry factors (gem) of up to 0.18 and 0.27, respectively, stemming from the formation of regular helical nanofibers on spin‐coated films via co‐assembly process after thermal annealing at 165 °C.
Breakthrough Study of CO2 Adsorption and Regeneration Performance of Mn‐ and Ce‐Doped Ni–Al Layered Double Hydroxides Derived Mixed Oxides in Packed‐Bed Column
Authors: Wagassa Ararso N. , Zereffa Enyew A. , Shifa Tofik A. , Bansiwal Amit
Published: February 2024

Carbon dioxide (CO2) capture is an important strategy to mitigate greenhouse gas emissions and reduce global warming effects. This study synthesizes two nanomaterials, Ce‐doped Ni–Al mixed metal oxide (CNAO) and Mn‐doped Ni–Al mixed metal oxide (MNAO), from Mn‐ and Ce‐doped Ni–Al‐layered double hydroxides using a co‐precipitation method followed by a calcination process. The materials are characterized using various techniques, such as High‐resolution transmission electron microscopy‐energy dispersive x‐ray spectroscopy/selected area electron dispersion (HRTEM‐EDS/SAED), X‐ray diffraction (XRD), x‐ray photoelectron spectroscopy (XPS), Brunauer‐Emmett‐Teller (BET), and attenuated total reflection Fourier transform infrared (ATR FT‐IR). The CO2 adsorption performance of the materials is evaluated using packed‐bed column experiments at the testing conditions of 13 vol% ± 1 vol% CO2 in N2 simulated flue gas, flow rate of 20 mL min−1, inlet pressure of 14.15 ± 0.1 psi, and temperature of 31 °C ± 2 °C. The results show that both CNAO and MNAO are promising nanomaterials for CO2 capture applications due to their high CO2 adsorption capacity and efficiency. CNAO has a higher saturation capacity of 11.4 mmol g−1 and a longer breakthrough time than MNAO, which has a saturation capacity of 10.0 mmol g−1. The doping of Ce and Mn enhances the CO2 adsorption capacity of the materials compared to the un‐doped Ni–Al mixed oxide. The mechanisms of CO2 adsorption are mainly linearly adsorbed CO2, bidentate, and monodentate or bulk carbonate formation, as revealed by ATR FT‐IR analysis. The regeneration performance results suggest that CNAO is more stable than MNAO under multiple regeneration cycles and more promising material for large‐scale CO2 capture applications.
Nitrosative Stress in Autism: Supportive Evidence and Implications for Mitochondrial Dysfunction
Authors: Frye Richard E. , Rose Shannon , Voinsky Irena , Gurwitz David
Published: February 2024

A recent study by the Amal team published in this journal in May 2023 proved for the first time the link of nitric oxide (NO) with autism spectrum disorder (ASD), thereby opening new venues for the potential use of neuronal nitric oxide synthase (nNOS) inhibitors as therapeutics for improving the neurological and behavioral symptoms of ASD. The authors conclude that their findings demonstrate that NO plays a significant role in ASD. Indeed, earlier studies support elevated NO and its metabolites, nitrite, and peroxynitrite, in individuals diagnosed with ASD. Dysregulated NOS activity may underlie the well‐documented mitochondrial dysfunction in a subset of individuals with ASD. Strategies for treating ASD shall also consider NO effects on mitochondrial respiration in modulating NOS activity. Further experimental evidence and controlled clinical trials with NOS modifiers are required for assessing their therapeutic potential for individuals with ASD.
Nanomaterials‐Induced Redox Imbalance: Challenged and Opportunities for Nanomaterials in Cancer Therapy
Authors: Wu Xumeng , Zhou Ziqi , Li Kai , Liu Shaoqin
Published: February 2024

Cancer cells typically display redox imbalance compared with normal cells due to increased metabolic rate, accumulated mitochondrial dysfunction, elevated cell signaling, and accelerated peroxisomal activities. This redox imbalance may regulate gene expression, alter protein stability, and modulate existing cellular programs, resulting in inefficient treatment modalities. Therapeutic strategies targeting intra‐ or extracellular redox states of cancer cells at varying state of progression may trigger programmed cell death if exceeded a certain threshold, enabling therapeutic selectivity and overcoming cancer resistance to radiotherapy and chemotherapy. Nanotechnology provides new opportunities for modulating redox state in cancer cells due to their excellent designability and high reactivity. Various nanomaterials are widely researched to enhance highly reactive substances (free radicals) production, disrupt the endogenous antioxidant defense systems, or both. Here, the physiological features of redox imbalance in cancer cells are described and the challenges in modulating redox state in cancer cells are illustrated. Then, nanomaterials that regulate redox imbalance are classified and elaborated upon based on their ability to target redox regulations. Finally, the future perspectives in this field are proposed. It is hoped this review provides guidance for the design of nanomaterials‐based approaches involving modulating intra‐ or extracellular redox states for cancer therapy, especially for cancers resistant to radiotherapy or chemotherapy, etc.
High‐Performance Hydrogel‐Encapsulated Engineered Exosomes for Supporting Endoplasmic Reticulum Homeostasis and Boosting Diabetic Bone Regeneration
Authors: Liu Yulan , Lin Sihan , Xu Zeqian , Wu Yuqiong , Wang Guifang , Yang Guangzheng , Cao Lingyan , Chang Haishuang , Zhou Mingliang , Jiang Xinquan
Published: February 2024

The regeneration of bone defects in diabetic patients still faces challenges, as the intrinsic healing process is impaired by hyperglycemia. Inspired by the discovery that the endoplasmic reticulum (ER) is in a state of excessive stress and dysfunction under hyperglycemia, leading to osteogenic disorder, a novel engineered exosome is proposed to modulate ER homeostasis for restoring the function of mesenchymal stem cells (MSCs). The results indicate that the constructed engineered exosomes efficiently regulate ER homeostasis and dramatically facilitate the function of MSCs in the hyperglycemic niche. Additionally, the underlying therapeutic mechanism of exosomes is elucidated. The results reveal that exosomes can directly provide recipient cells with SHP2 for the activation of mitophagy and elimination of mtROS, which is the immediate cause of ER dysfunction. To maximize the therapeutic effect of engineered exosomes, a high‐performance hydrogel with self‐healing, bioadhesive, and exosome‐conjugating properties is applied to encapsulate the engineered exosomes for in vivo application. In vivo, evaluation in diabetic bone defect repair models demonstrates that the engineered exosomes delivering hydrogel system intensively enhance osteogenesis. These findings provide crucial insight into the design and biological mechanism of ER homeostasis‐based tissue‐engineering strategies for diabetic bone regeneration.
Unveiling Favorable Microenvironment on Porous Doped Carbon Nanosheets for Superior H2O2 Electrosynthesis in Neutral Media
Authors: Jing Lingyan , Tian Qiang , Wang Wenyi , Li Xuan , Hu Qi , Yang Hengpan , He Chuanxin
Published: February 2024

Designing effective electrocatalysts tailored for targeted reactions requires fundamental insights into the structure dependence of the reaction microenvironment. Herein, inspired by finite element simulations, N,O co‐doped carbon nanosheets featuring a hierarchical micro/mesoporous structure to form an oxygen‐rich and local alkaline‐like microenvironment for the two‐electron oxygen reduction reaction (2e− ORR) in a neutral medium are designed. The in situ and ex situ test results confirmed that the micro/mesoporous carbon architecture can elevate the local pH and accelerate the generation of intermediates (*O2, *OOH), leading to high‐efficiency H2O2 production. Utilizing this favorable microenvironment, N,O‐CNS0.5 demonstrated exceptional H2O2 electrosynthesis performance in neutral media, achieving a superior H2O2 yield rate (6705 mmol gcatalyst−1 h−1 in a flow cell). Additionally, comparative experiments and density‐functional theory calculations provided confirmation of the bi‐doping of N and O as the active origin responsible for the electrochemical 2e− ORR. This study synergistically manipulates the reaction microenvironment and active sites, providing an opportunity for efficient H2O2 electro‐production in a neutral medium.
Ultrathin Reed Membranes: Nature's Intimate Ion‐Regulation Skins Safeguarding Zinc Metal Anodes in Aqueous Batteries
Authors: Huang Zien , Yang Shanchen , Zhang Ying , Zhang Yaxin , Xue Rongrong , Ma Yue , Wang Zhaohui
Published: February 2024

The practical realization of aqueous zinc‐ion batteries relies crucially on effective interphases governing Zn electrodeposition chemistry. In this study, an innovative solution by introducing an ultrathin (≈2 µm) biomass membrane as an intimate artificial interface, functioning as nature's ion‐regulation skin to protect zinc metal anodes is proposed. Capitalizing on the inherent properties of natural reed membrane, including multiscale ion transport tunnels, abundant ─OH groups, and remarkable mechanical integrity, the reed membrane demonstrates efficacy in regulating uniform and rapid Zn2+ transport, promoting desolvation, and governing Zn (002) plane electrodeposition. Importantly, a unique in situ electrochemical Zn─O bond formation mechanism between the reed membrane and Zn electrode upon cycling is elucidated, resulting in a robustly adhered interface covering on the zinc anode surface, ultimately ensuring remarkable dendrite‐free and highly reversible Zn anodes. Consequently, the approach achieves a prolonged cycle life for over 1450 h at 3 mA cm−2/1.5 mAh cm−2 in symmetric Zn//Zn cells. Moreover, exceptional cyclic performance (88.95%, 4000 cycles) is obtained in active carbon‐based cells with an active mass loading of 5.8 mg cm−2. The approach offers a cost‐effective and environmentally friendly strategy for achieving stable and reversible zinc anodes for aqueous batteries.
Journey through diagnosis
Authors: Yaghy Antonio
Published: February 2024

This reflective poem explores the profound human impact of receiving a serious medical diagnosis. The speaker grapples with the emotional upheaval of this sudden severing from one's presumed healthy future. There are attempts to cling to denial or bargain for a different outcome. But the truth of the diagnosis persists, sending ripples of change throughout the patient's life. Dreams slip away and plans evaporate in the crucible of illness. After a struggle, the mind makes peace and courageously leans into the difficulties ahead. The poem celebrates the human capacity to accept vulnerability, find gifts within trials, and walk the remaining road with wisdom. It reflects on how a diagnosis can heighten awareness that life is fleeting and precious. The accompanying digital artwork was generated using OpenAI's DALL·E 3 and modified using Adobe Firefly. It is a stark, black canvas, which can be seen as a metaphor for the profound and contemplative journey described patients go through. It symbolizes the inner darkness and uncertainty faced when confronting life‐altering diagnoses, echoing the feelings of isolation, the search for meaning, and the gradual acceptance of a new reality as one navigates through the trials of illness.
C1ql3knockout affects microglia activation, neuronal integrity, and spontaneous behavior in Wistar rats
Authors: Zhang Li , Dong Wei , Li Jingwen , Gao Shan , Sheng Hanxuan , Kong Qi , Guan Feifei , Zhang Lianfeng
Published: February 2024

Background

C1QL3 is widely expressed in the brain and is specifically produced by a subset of excitatory neurons. However, its function is still not clear. We establishedC1ql3‐deficient rats to investigate the role of C1QL3 in the brain.

Methods

C1ql3knockout (KO) rats were generated using CRISPR/Cas9.C1ql3KO was determined by polymerase chain reaction (PCR), DNA sequencing, and western blotting. Microglia morphology and cytokine expression with or without lipopolysaccharide (LPS) stimulus were analyzed using immunohistochemistry and real‐time PCR. The brain structure changes in KO rats were examined using magnetic resonance imaging. Neuronal architecture alteration was analyzed by performing Golgi staining. Behavior was evaluated using the open field test, Morris water maze test, and Y maze test.

Results

C1ql3KO significantly increased the number of ramified microglia and decreased the number of hypertrophic microglia, whereasC1ql3KO did not influence the expression of pro‐inflammatory factors and anti‐inflammatory factors except IL‐10.C1ql3KO brains had more amoeboid microglia types and higher Arg‐1 expression compared with the WT rats after LPS stimulation. The brain weights and HPC sizes ofC1ql3KO rats did not differ from WT rats.C1ql3KO damaged neuronal integrity including neuron dendritic arbors and spine density.C1ql3KO rats demonstrated an increase in spontaneous activity and an impairment in short working memory.

Conclusions

C1ql3KO not only interrupts the neuronal integrity but also affects the microglial activation, resulting in hyperactive behavior and impaired short memory in rats, which highlights the role of C1QL3 in the regulation of structure and function of both neuronal and microglial cells.
Flu‐CED: A comparative transcriptomics database of influenza virus‐infected human and animal models
Authors: Wu Yue , Wang Jue , Xue Jing , Xiang Zhiguang , Guo Jianguo , Zhan Lingjun , Wei Qiang , Kong Qi
Published: February 2024

Background

The continuing emergence of influenza virus has highlighted the value of public databases and related bioinformatic analysis tools in investigating transcriptomic change caused by different influenza virus infections in human and animal models.

Methods

We collected a large amount of transcriptome research data related to influenza virus‐infected human and animal models in public databases (GEO and ArrayExpress), and extracted and integrated array and metadata. The gene expression matrix was generated through strictly quality control, balance, standardization, batch correction, and gene annotation. We then analyzed gene expression in different species, virus, cells/tissues or after antibody/vaccine treatment and imported sample metadata and gene expression datasets into the database.

Results

Overall, maintaining careful processing and quality control, we collected 8064 samples from 103 independent datasets, and constructed a comparative transcriptomics database of influenza virus named the Flu‐CED database (Influenza comparative expression database, https://flu.com‐med.org.cn/). Using integrated and processed transcriptomic data, we established a user‐friendly website for realizing the integration, online retrieval, visualization, and exploration of gene expression of influenza virus infection in different species and the biological functions involved in differential genes. Flu‐CED can quickly query single and multi‐gene expression profiles, combining different experimental conditions for comparative transcriptome analysis, identifying differentially expressed genes (DEGs) between comparison groups, and conveniently finding DEGs.

Conclusion

Flu‐CED provides data resources and tools for analyzing gene expression in human and animal models infected with influenza virus that can deepen our understanding of the mechanisms underlying disease occurrence and development, and enable prediction of key genes or therapeutic targets that can be used for medical research.
Seizure Cycles under Pharmacotherapy
Authors: Friedrichs‐Maeder Cecilia , Proix Timothée , Tcheng Thomas K. , Skarpaas Tara , Rao Vikram R. , Baud Maxime O.
Published: February 2024

Objective

This study was undertaken to determine the effects of antiseizure medications (ASMs) on multidien (multiday) cycles of interictal epileptiform activity (IEA) and seizures and evaluate their potential clinical significance.

Methods

We retrospectively analyzed up to 10 years of data from 88 of the 256 total adults with pharmacoresistant focal epilepsy who participated in the clinical trials of the RNS System, an intracranial device that keeps records of IEA counts. Following adjunctive ASM trials, we evaluated changes over months in (1) rates of self‐reported disabling seizures and (2) multidien IEA cycle strength (spectral power for periodicity between 4 and 40 days). We used a survival analysis and the receiver operating characteristics to assess changes in IEA as a predictor of seizure control.

Results

Among 56 (33.3%) of the 168 adjunctive ASM trials suitable for analysis, ASM introduction was followed by an average 50 to 70% decrease in multidien IEA cycle strength and a concomitant 50 to 70% decrease in relative seizure rate for up to 12 months. Individuals with a ≥50% decrease in IEA cycle strength in the first 3 months of an ASM trial had a higher probability of remaining seizure responders (≥50% seizure rate reduction, p < 10−7) or super‐responders (≥90%, p < 10−8) over the next 12 months.

Interpretation

In this large cohort, a decrease in multidien IEA cycle strength following initiation of an adjunctive ASM correlated with seizure control for up to 12 months, suggesting that fluctuations in IEA mirror “disease activity” in pharmacoresistant focal epilepsy and may have clinical utility as a biomarker to predict treatment response. ANN NEUROL 2024;95:743–753
Integrating Olefin Carboamination and Hofmann‐Löffler‐Freytag Reaction by Radical Deconstruction of Hydrazonyl N−N Bond
Authors: Hu Si‐Pei , Gao Chen‐Hui , Liu Tu‐Ming , Miao Bing‐Yang , Wang Hong‐Chen , Yu Wei , Han Bing
Published: February 2024

As a type of elementary organic compounds containing N−N single bond, hydrazone involved chemical conversions are extremely extensive, but they are mainly limited to N2‐retention and N2‐removal modes. We report herein an unprecedented protocol for the realization of division utilization of the N2‐moiety of hydrazone by a radical facilitated N−N bond deconstruction strategy. This new conversion mode enables the successful combination of alkene carboamination and Hofmann‐Löffler‐Freytag reaction by the reaction of N‐homoallyl mesitylenesulfonyl hydrazones with ethyl difluoroiodoacetate under photocatalytic redox neutral conditions. Mechanism studies reveal that the reaction undergoes a radical relay involving addition, crucial remote imino‐N migration and H‐atom transfer. Consequently, a series of structurally significant ϵ‐N‐sulphonamide‐α,α‐difluoro‐γ‐amino acid esters are efficiently produced via continuous C−C bond and dual C−N bonds forging.
Amperometry and Electron Microscopy show Stress Granules Induce Homotypic Fusion of Catecholamine Vesicles
Authors: Gu Hui , Gu Chaoyi , Locker Nicolas , Ewing Andrew G.
Published: February 2024

An overreactive stress granule (SG) pathway and long‐lived, stable SGs formation are thought to participate in the progress of neurodegenerative diseases (NDs). To understand if and how SGs contribute to disorders of neurotransmitter release in NDs, we examined the interaction between extracellular isolated SGs and vesicles. Amperometry shows that the vesicular content increases and dynamics of vesicle opening slow down after vesicles are treated with SGs, suggesting larger vesicles are formed. Data from transmission electron microscopy (TEM) clearly shows that a portion of large dense‐core vesicles (LDCVs) with double/multiple cores appear, thus confirming that SGs induce homotypic fusion between LDCVs. This might be a protective step to help cells to survive following high oxidative stress. A hypothetical mechanism is proposed whereby enriched mRNA or protein in the shell of SGs is likely to bind intrinsically disordered protein (IDP) regions of vesicle associated membrane protein (VAMP) driving a disrupted membrane between two closely buddled vesicles to fuse with each other to form double‐core vesicles. Our results show that SGs induce homotypic fusion of LDCVs, providing better understanding of how SGs intervene in pathological processes and opening a new direction to investigations of SGs involved neurodegenerative disease.
Dimeric Giant Molecule Acceptors Featuring N‐type Linker: Enhancing Intramolecular Coupling for High‐Performance Polymer Solar Cells
Authors: Fu Hongyuan , Wang Qingyuan , Chen Qi , Zhang Yaogang , Meng Shixin , Xue Lingwei , Zhang Chunfeng , Yi Yuanping , Zhang Zhi‐Guo
Published: February 2024

Giant molecular acceptors (GMAs) are typically designed through the conjugated linking of individual small molecule acceptors (SMAs). This design imparts an extended molecular size, elevating the glass transition temperature (Tg) relative to their SMA counterparts. Consequently, it effectively suppresses the thermodynamic relaxation of the acceptor component when blended with polymer donors to construct stable polymer solar cells (PSCs). Despite their merits, the optimization of their chemical structure for further enhancing of device performance remains challenge. Different from previous reports utilizing p‐type linkers, here, we explore an n‐type linker, specifically the benzothiadiazole unit, to dimerize the SMA units via a click‐like Knoevenagel condensation, affording BT‐DL. In comparison with B‐DL with a benzene linkage, BT‐DL exhibits significantly stronger intramolecular super‐exchange coupling, a desirable property for the acceptor component. Furthermore, BT‐DL demonstrates a higher film absorption coefficient, redshifted absorption, larger crystalline coherence, and higher electron mobility. These inherent advantages of BT‐DL translate into a higher power conversion efficiency of 18.49 % in PSCs, a substantial improvement over the 9.17 % efficiency observed in corresponding devices with B‐DL as the acceptor. Notably, the BT‐DL based device exhibits exceptional stability, retaining over 90 % of its initial efficiency even after enduring 1000 hours of thermal stress at 90 °C. This work provides a cost‐effective approach to the synthesis of n‐type linker‐dimerized GMAs, and highlight their potential advantage in enhancing intramolecular coupling for more efficient and durable photovoltaic technologies.
From 2D slices to a 3D model: Training students in digital microanatomy analysis techniques through a 3D printed neuron project
Authors: Renna Jordan M. , Sondereker Katelyn B. , Cors Christopher L. , Chaszeyka Sara N. , Keenan Kristin N. , Corigliano Michael R. , Milgrom Lindsey A. , Onyak Jessica R. , Hamad Edward J. , Stabio Maureen E.
Published: February 2024

The reconstruction of two‐dimensional (2D) slices to three‐dimensional (3D) digital anatomical models requires technical skills and software that are becoming increasingly important to the modern anatomist, but these skills are rarely taught in undergraduate science classrooms. Furthermore, learning opportunities that allow students to simultaneously explore anatomy in both 2D and 3D space are increasingly valuable. This report describes a novel learning activity that trains students to digitally trace a serially imaged neuron from a confocal stack and to model that neuron in 3D space for 3D printing. By engaging students in the production of a 3D digital model, this learning activity is designed to provide students a novel way to enhance their understanding of the content, including didactic knowledge of neuron morphology, technical research skills in image analysis, and career exploration of neuroanatomy research. Moreover, students engage with microanatomy in a way that starts in 2D but results in a 3D object they can see, touch, and keep. This discursive article presents the learning activity, including videos, instructional guides, and learning objectives designed to engage students on all six levels of Bloom's Taxonomy. Furthermore, this work is a proof of principle modeling workflow that is approachable, inexpensive, achievable, and adaptable to cell types in other organ systems. This work is designed to motivate the expansion of 3D printing technology into microanatomy and neuroanatomy education.
An Isolable THF‐Coordinated Dialkylgermanone
Authors: Oshima Kazuma , Kobayashi Ryo , Sakamoto Kengo , Yoza Kenji , Ishida Shintaro , Iwamoto Takeaki
Published: February 2024

A stable dialkylgermanone was generated by mixing a solid of the corresponding dialkylgermylene and gaseous N2O. While the dialkylgermanone is marginally persistent in solution and gradually converts to its head‐to‐tail dimer at room temperature, the addition of THF to the dialkylgermanone provided an isolable THF‐coordinated dialkylgermanone. The THF‐coordinated dialkylgermanone reacts with H2O, THF, and B(C6F5)3 similar to the corresponding base‐free two‐coordinate dialkylsilanone. The dialkylgermanone undergoes deoxygenation in the presence of triphenylphosphine to provide the corresponding germylene and olefination upon treatment with phosphaylide Ph3PCHPh to afford the corresponding Ge=C bond compound (germa‐Wittig reaction).
Integrative ATAC‐seq and RNA‐seq analysis associated with diabetic nephropathy and identification of novel targets for treatment by dapagliflozin
Authors: Shen Jianxiao , Ying Liang , Wu Jiajia , Fang Yan , Zhou Wenyan , Qi Chaojun , Gu Leyi , Mou Shan , Yan Yuru , Tian Ming , Ni Zhaohui , Che Xiajing
Published: February 2024

Dapagliflozin (DAPA) are clinically effective in improving diabetic nephropathy (DN). However, whether and how chromatin accessibility changed by DN responds to DAPA treatment is unclear. Therefore, we performed ATAC‐seq, RNA‐seq, and weighted gene correlation network analysis to identify the chromatin accessibility, the messenger RNA (mRNA) expression, and the correlation between clinical phenotypes and mRNA expression using kidney from three mouse groups: db/m mice (Controls), db/db mice (case group), and those treated with DAPA (treatment group). RNA‐Seq and ATAC‐seq conjoint analysis revealed many overlapping pathways and networks suggesting that the transcriptional changes of DN and DAPA intervention largely occured dependently on chromatin remodeling. Specifically, the results showed that some key signal transduction pathways, such as immune dysfunction, glucolipid metabolism, oxidative stress and xenobiotic and endobiotic metabolism, were repeatedly enriched in the analysis of the RNA‐seq data alone, as well as combined analysis with ATAC‐seq data. Furthermore, we identified some candidate genes (UDP glucuronosyltransferase 1 family, Dock2, Tbc1d10c, etc.) and transcriptional regulators (KLF6 and GFI1) that might be associated with DN and DAPA restoration. These reversed genes and regulators confirmed that pathways related to immune response and metabolism pathways were critically involved in DN progression.
Zona pellucida removal resulted in a successful live birth: Report on a case with recurrent implantation failure due to embryonic bacteria contamination
Authors: Dang Son Truong , Tran Huy Phuong , Ho Tuong Nguyen , Ly Loc Thai , Hoang Tuyet Thi‐Diem , Huynh Trang Nguyen‐Khanh , Do Anh Tuan , Nguyen Thuan Duc , Dao Phuong Thi
Published: February 2024

Key clinical message

In in vitro fertilization (IVF), laser offers several advantages. In this study, we employed laser to eliminate the zona pellucida of a contaminated embryo. This approach helps to rescue embryo with bacterial contamination, and improve embryo‐endometrium interaction.

To present a case report on the removal of a contaminated zona pellucida from an embryo of patient with a history of recurrent implantation failure (RIF), which was followed by a successful live birth. We present the case of a 34‐year‐old patient with a history of 3 years of infertility who underwent in vitro fertilization. During the culture process, the embryos became contaminated, leading to three failed implantations. Despite the aneuploidy of the embryo and the implementation of a washing technique, the contamination persisted. In the final attempt, the contaminated zona pellucida was successfully removed using laser, followed by embryo transfer, resulting in a live birth. We provided detailed clinical information, including patient demographics, infertility history, ovarian response, evidence of bacterial contamination, embryo development, treatment protocols, and outcomes. Laser excision of the zona pellucida is a safe and effective method for addressing bacterial infection in embryos.
Case report of congenital neutropenia type 4 with glucose‐6‐phosphatase catalytic subunit 3 (G6PC3) deficiency
Authors: Dhayhi Nabil S. , Mahnashi Mohammed A. , Mokhasha Alanoud I. , Ahmed Lana F. , Shamakhi Ahmed E. , Ageel Adeeb A. , Tohary Mohammed A. , Alhazmi Abdulaziz H.
Published: February 2024

Key Clinical Message

Congenital neutropenia syndromes encompass a group of genetic disorders characterized by persistent neutropenia and recurrent infections inherited in an autosomal recessive, dominant, or X‐linked manner. These syndromes arise from mutations in various genes, and one of the significant genes involved is glucose‐6‐phosphatase catalytic subunit 3 (G6PC3), giving rise to a condition known as Dursun syndrome. As per existing knowledge, a total of 92 cases of Dursun syndrome have been reported globally, including eight cases from Saudi Arabia. Our study identified two additional cases exhibiting neutropenia since the early postnatal period and recurrent admissions due to infections. Additionally, these patients presented with oral ulcers, chronic diarrhea, and anomalies affecting the cardiac and genitourinary systems. The rising incidence of congenital neutropenia on a global scale necessitates heightened vigilance among clinicians to ensure thorough follow‐up of patients with neutropenia. This proactive approach can lead to early detection and appropriate management of associated complications, ultimately improving patient outcomes.
Acute myeloid leukemia with unreported translocation (x; 3) (q24; p13): A case report
Authors: Gholami Nasrin , Khalaji Amirreza , Mehri Maghsood , Mehrtabar Saba , Habibzade Elham
Published: February 2024

Key Clinical Message

Novel and rare chromosomal aberrations in AML are important to understand, particularly if associated with tumorigenesis and how they contribute to prognostic risk. It is important that acute leukemia be treated right away. Herein, novel (x; 3) (q24; p13) is described.

Acute myeloid leukemia (AML) is a cancer of the blood and bone marrow. It is the most common type of acute leukemia in adults. This type of cancer usually gets worse quickly if it is not treated. Here, we report an unusual case of AML with an unreported translocation associated with AML.
Cyclic Deracemization of rac‐Sulfoxides via Alternating Biocatalytic Reduction and Light‐Dependent Oxidation Employing Eosin Y as Photocatalyst
Authors: Bierbaumer Sarah , Glueck Silvia M. , Winkler Christoph K. , Kroutil Wolfgang
Published: February 2024

The synergistic combination of biocatalysis and photocatalysis is emerging as powerful tool for the development of sustainable and atom‐efficient synthetic concepts facilitating an enormous portfolio of possible reactions which even goes beyond the capabilities found in nature. Here, a cyclic deracemization process is presented tailored for the synthesis of optically pure sulfoxides which are versatile structural motifs in asymmetric synthesis as well as in bioactive compounds. Enantioselective enzyme‐catalyzed reduction of rac‐sulfoxides was combined with a stereo‐unselective photocatalytic oxidation of the corresponding sulfide intermediate. The utilization of the readily accessible and rather inexpensive photocatalyst Eosin Y increases the usability of this synthetic method. To overcome the incompatibility between the photocatalyst Eosin Y and the biocatalytic step, the cyclic deracemization process was performed in a step‐wise fashion via alternated reduction in the darkness and oxidation under illumination. This modular system allowed precise adjustments of reaction parameters yielding the desired sulfoxide targets with up to >99 % ee. Evaluation of the substrate scope including a range of structurally diverse molecules demonstrated its broad applicability.
Gadolinium Doped Ceria as Nickel–Free Fuel Electrode in High Temperature CO2‐Electrolysis
Authors: Uecker Jan , Unachukwu Ifeanyichukwu D. , Vibhu Vaibhav , Vinke Izaak C. , de Haart L. G. J. (Bert) , Eichel Rüdiger‐A.
Published: February 2024

In this work, the performance, electrochemical processes, and stability of GDC (Ce0.8Gd0.2O1.9) fuel electrode containing single cells (GDC/8YSZ/GDC/LSCF) were examined in CO2 electrolysis conditions. The current density and area specific resistance is determined for different operation conditions. The examined cells showed a higher performance compared to state‐of‐the‐art Ni−YSZ fuel electrode (Ni‐YSZ/8YSZ/GDC/LSCF) based single cells with a similar production route. Furthermore, the cells were examined by means of electrochemical impedance spectroscopy (EIS) and the recorded data were evaluated by the distribution of relaxation times (DRT) analysis. An equivalent circuit model (ECM) consisting of four time constants and a Gerischer impedance (LR−RQ1−RQ2−G−RQ4−RQ5) was established to gain further insight into the individual processes in the cells. For instance, the low–frequency process P5 referring to RQ5 is the rate‐determining step in CO2 electrolysis and is assigned to a surface reaction including the charge transfer and possibly the gas diffusion in the GDC fuel electrode. A long–term stability test was performed in CO2 electrolysis conditions at 900 °C with a constant current load of −0.5 A ⋅ cm−2 for up to 1200 h. A degradation rate of 62 mV ⋅ kh−1 was observed. By EIS analysis, a similar contribution of the ohmic and polarization resistances to the degradation was determined. The low–frequency process P5 and thus the surface reaction including the charge transfer in the GDC fuel electrode is contributing most to the increase in polarization resistance. After the long–term stability test, scanning electron microscopy (SEM) analysis was carried out and a coarsening of GDC particles in the fuel electrode was observed.
Toward Lung Ventilation Imaging Using Hyperpolarized Diethyl Ether Gas Contrast Agent
Authors: Ariyasingha Nuwandi M. , Chowdhury Md Raduanul H. , Samoilenko Anna , Salnikov Oleg G. , Chukanov Nikita V. , Kovtunova Larisa M. , Bukhtiyarov Valerii I. , Shi Zhongjie , Luo Kehuan , Tan Sidhartha , Koptyug Igor V. , Goodson Boyd M. , Chekmenev Eduard Y.
Published: February 2024

Hyperpolarized 129Xe gas was FDA‐approved as an inhalable contrast agent for magnetic resonance imaging of a wide range of pulmonary diseases in December 2022. Despite the remarkable success in clinical research settings, the widespread clinical translation of HP 129Xe gas faces two critical challenges: the high cost of the relatively low‐throughput hyperpolarization equipment and the lack of 129Xe imaging capability on clinical MRI scanners, which have narrow‐bandwidth electronics designed only for proton (1H) imaging. To solve this translational grand challenge of gaseous hyperpolarized MRI contrast agents, here we demonstrate the utility of batch‐mode production of proton‐hyperpolarized diethyl ether gas via heterogeneous pairwise addition of parahydrogen to ethyl vinyl ether. An approximately 0.1‐liter bolus of hyperpolarized diethyl ether gas was produced in 1 second and injected in excised rabbit lungs. Lung ventilation imaging was performed using sub‐second 2D MRI with up to 2×2 mm2 in‐plane resolution using a clinical 0.35 T MRI scanner without any modifications. This feasibility demonstration paves the way for the use of inhalable diethyl ether as a gaseous contrast agent for pulmonary MRI applications using any clinical MRI scanner.