bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurochemical Monitoring of Glycerol Therapy in Patients With Ischemic Brain Edema
Authors: Berger Christian , Sakowitz Oliver W. , Kiening Karl L. , Schwab Stefan
Published: December 2004

Background and Purpose—

Osmotic agents such as glycerol are used to treat brain edema in stroke patients. We investigated the pharmacokinetics of glycerol in brain tissue by cerebral microdialysis.

Methods—

Patients experiencing large middle cerebral artery infarction were included in this prospective study. The following variables were assessed before and every 10 minutes until 80 minutes after intravenous administration of 25 g of glycerol: intracranial pressure (ICP), serum osmolarity, and cerebral microdialysate concentrations of glycerol, glutamate, pyruvate, and lactate.

Results—

During 16 ICP crises in 7 patients, cerebral glycerol concentrations (baseline 73.9±17.0 μmol/L) increased immediately after glycerol administration by up to 350%. Conversely, ICP (baseline 25±2.4 mm Hg) rapidly decreased by almost 50%. Both effects lasted for 70 minutes. Serum osmolarity (baseline 305±5.6 mOsm/L) was only briefly raised, whereas glutamate, lactate, and pyruvate remained unaffected.

Conclusion—

Treatment of stroke patients with intravenous glycerol has only a brief effect on plasma osmolarity, but a more sustained effect on ICP, which is, however, accompanied by a rapid glycerol accumulation in brain tissue.
Are There Inequalities in the Provision of Stroke Care?
Authors: McKevitt Christopher , Coshall Catherine , Tilling Kate , Wolfe Charles
Published: December 2004

Background and Purpose—

There is evidence of unequal access to health care interventions even where universal health systems operate. We investigated associations between patients’ sociodemographic characteristics and the provision of acute and longer-term stroke care in a multiethnic urban population.

Methods—

We used data from 1635 patients with first-ever stroke, collected by a population-based stroke register from 1995 to 2000. Using multivariable analyses, controlled for sociodemographic and clinical factors, we investigated access to 22 evidence-based components of care.

Results—

1392 patients (85.1%) were admitted to hospital; of these, 354 (25.4%) were admitted or transferred to a stroke unit. Of those with clinical need, 607 (70.7%) received physical therapies; 477 (59.8%) received speech and language therapy. Older age was associated with lower odds of hospitalization (odds ratio [OR], 0.50; 95% CI, 0.32 to 0.77,
P
=0.02) and diagnostic brain imaging (OR, 0.15; 95% CI, 0.08 to 0.30,
P
<0.01) but higher odds of receiving physical therapy (OR, 4.24; 95% CI, 1.22 to 14.73,
P
<0.01). Black ethnicity was associated with higher odds of stroke unit admission (OR, 1.59; 95% CI, 1.01 to 2.49,
P
<0.04). There was a weak association between socioeconomic status and admission to hospital and stroke unit. Gender was associated only with treatment of hypertension before stroke.

Conclusions—

Provision of individual components of care over 1 year varied for specific sociodemographic categories, but there was no consistent pattern of inequality. Clinical decision-making processes are likely to influence these patterns. Further information about clinician and patient roles in decision making is required.
Control of lymphocyte shape and the chemotactic response by the GTP exchange factor Vav
Authors: Vicente-Manzanares Miguel , Cruz-Adalia Aranzazu , Martín-Cófreces Noa B. , Cabrero José R. , Dosil Mercedes , Alvarado-Sánchez Brenda , Bustelo Xosé R. , Sánchez-Madrid Francisco
Published: December 2004

Rho GTPases control many facets of cell polarity and migration; namely, the reorganization of the cellular cytoskeleton to extracellular stimuli. Rho GTPases are activated by GTP exchange factors (GEFs), which induce guanosine diphosphate (GDP) release and the stabilization of the nucleotide-free state. Thus, the role of GEFs in the regulation of the cellular response to extracellular cues during cell migration is a critical step of this process. In this report, we have analyzed the activation and subcellular localization of the hematopoietic GEF Vav in human peripheral blood lymphocytes stimulated with the chemokine stromal cell–derived factor-1 (SDF-1α). We show a robust activation of Vav and its redistribution to motility-associated subcellular structures, and we provide biochemical evidence of the recruitment of Vav to the membrane of SDF-1α–activated human lymphocytes, where it transiently interacts with the SDF-1α receptor CXCR4. Overexpression of a dominant negative form of Vav abolished lymphocyte polarization, actin polymerization, and migration. SDF-1α–mediated cell polarization and migration also were impaired by overexpression of an active, oncogenic Vav, although the mechanism appears to be different. Together, our data postulate a pivotal role for Vav in the transmission of the migratory signal through the chemokine receptor CXCR4.
Suppression of apoptosis by bcl-2 overexpression in lymphoid cells of transgenic zebrafish
Authors: Langenau David M. , Jette Cicely , Berghmans Stephane , Palomero Teresa , Kanki John P. , Kutok Jeffery L. , Look A. Thomas
Published: December 2004

The zebrafish is an attractive vertebrate model for genetic studies of development, apoptosis, and cancer. Here we describe a transgenic zebrafish line in which T- and B-lymphoid cells express a fusion transgene that encodes the zebrafish bcl-2 protein fused to the enhanced green fluorescence protein (EGFP). Targeting EGFP-bcl-2 to the developing thymocytes of transgenic fish resulted in a 2.5-fold increase in thymocyte numbers and a 1.8-fold increase in GFP-labeled B cells in the kidney marrow. Fluorescent microscopic analysis of living rag2-EGFP-bcl-2 transgenic fish showed that their thymocytes were resistant to irradiation- and dexamethasone-induced apoptosis, when compared with control rag2-GFP transgenic zebrafish. To test the ability of bcl-2 to block irradiation-induced apoptosis in malignant cells, we compared the responsiveness of Myc-induced leukemias with and without EGFP-bcl-2 expression in living transgenic zebrafish. T-cell leukemias induced by the rag2-EGFP-Myc transgene were ablated by irradiation, whereas leukemias in double transgenic fish expressing both Myc and EGFP-bcl-2 were resistant to irradiation-induced apoptotic cell death. The forward genetic capacity of the zebrafish model system and the ability to monitor GFP-positive thymocytes in vivo make this an ideal transgenic line for modifier screens designed to identify genetic mutations or small molecules that modify bcl-2-mediated antiapoptotic pathways. (Blood. 2005;105:3278-3285)
The development of imatinib as a therapeutic agent for chronic myeloid leukemia
Authors: Deininger Michael , Buchdunger Elisabeth , Druker Brian J.
Published: December 2004

Imatinib has revolutionized drug therapy of chronic myeloid leukemia (CML). Preclinical studies were promising but the results of clinical trials by far exceeded expectations. Responses in chronic phase are unprecedented, with rates of complete cytogenetic response (CCR) of more than 40% in patients after failure of interferon-α (IFN) and more than 80% in newly diagnosed patients, a level of efficacy that led to regulatory approval in record time. While most of these responses are stable, resistance to treatment after an initial response is common in more advanced phases of the disease. Mutations in the kinase domain (KD) of BCR-ABL that impair imatinib binding have been identified as the leading cause of resistance. Patients with CCR who achieve a profound reduction of BCR-ABL mRNA have a very low risk of disease progression. However, residual disease usually remains detectable with reverse transcription–polymerase chain reaction (RT-PCR), indicating that disease eradication may pose a significant challenge. The mechanisms underlying the persistence of minimal residual disease are unknown. In this manuscript, we review the preclinical and clinical development of imatinib for the therapy of CML, resistance and strategies that may help to eliminate resistant or residual leukemia.
Differential effect of LFA703, pravastatin, and fluvastatin on production of IL-18 and expression of ICAM-1 and CD40 in human monocytes
Authors: Takahashi Hideo Kohka , Mori Shuji , Iwagaki Hiromi , Yoshino Tadashi , Tanaka Noriaki , Weitz-Schmidt Gabriele , Nishibori Masahiro
Published: December 2004

A novel, proinflammatory cytokine, interleukin (IL)-18 production was detected in the medium of human monocytes treated with 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase inhibitors, pravastatin, and fluvastatin (0.1 and 1 μM) but not with the statin-derived lymphocyte function-associated antigen-1 (LFA-1) inhibitor LFA703, which did not inhibit HMG-CoA reductase. Pravastatin and fluvastatin also induced the production of IL-18, tumor necrosis factor α (TNF-α) and interferon-γ (IFN-γ) in human peripheral blood mononuclear cells (PBMC) in contrast to LFA703. IL-18 production by PBMC is located upstream of the cytokine cascade activated by these statins. The IL-18-induced cytokine production was demonstrated to be dependent on adhesion molecule expression on monocytes. In the absence and presence of lower concentrations (0.1 and 1 ng/ml) of IL-18, pravastatin and fluvastatin inhibited the expression of intercellular adhesion molecule (ICAM)-1 and induced the expression of CD40, whereas LFA703 had no effect. In the presence of higher concentrations (5, 10, and 100 ng/ml) of IL-18, pravastatin, fluvastatin, and LFA703 similarly inhibited the expression of ICAM-1 and CD40 as well as the production of IL-12, TNF-α, and IFN-γ in PBMC. The effects of pravastatin and fluvastatin but not LFA703 were abolished by the addition of mevalonate, indicating the involvement of HMG-CoA reductase in the action of pravastatin and fluvastatin. Thus, the effects of LFA703 were distinct from those of pravastatin and fluvastatin in the presence of lower concentrations of IL-18. It was concluded that LFA703 has the inhibitory effect on an IL-18-initiated immune response without any activation on monocytes.
Novel Association of Vav2 and Nek3 Modulates Signaling through the Human Prolactin Receptor
Authors: Miller Sommer L. , DeMaria Jamie E. , Freier David O. , Riegel Angela M. , Clevenger Charles V.
Published: December 2004

Prolactin (PRL) receptor activation contributes to the progression and motility of human breast cancer. This event activates multimeric signaling pathways, including the activation of the Vav family of guanine nucleotide exchange factors. To detect novel proteins interacting with Vav, yeast two-hybrid analysis was performed and demonstrated an interaction between the serine/threonine NIMA (never in mitosis A)-related family kinase p56Nek3 and Vav1. The PRL-dependent interaction of Nek3 with Vav1 and Vav2 was confirmed by coimmunoprecipitation analysis. PRL stimulation of T47D cells induced Nek3 kinase activity and the interaction of Vav2/Nek3 with the PRL receptor. Increased Nek3 levels up-regulated Vav2 serine and tyrosine phosphorylation, whereas knockdown of Nek3 resulted in a reduction of Vav2 phosphorylation. Activation of guanosine triphosphatase Rac-1 in Chinese hamster ovary transfectants required both Nek3 and Vav2 and was inhibited by the overexpression of a kinase inactivating Nek3 mutant. However, overexpression of either Nek3 or kinase-inactive Nek3 had no effect on Vav2-potentiated signal transducer and activator of transcription 5-mediated gene expression. Overexpression of kinase inactive Nek3 in T47D cells led to a 50% increase in apoptosis vs. controls. These data suggest that the PRL-mediated activation of Nek3 contributes differentially to Vav2 signaling pathways involving Rac1 and signal transducer and activator of transcription 5 and implicates Nek3 during PRL-mediated actions in breast cancer.
Fever, Rash, and Shortness of Breath in a 69-Year-Old
Authors: Tiwari Vivekanand , Miller Alexander T.
Published: February 2024

A 69-year-old had fever, fatigue, rash, right periorbital swelling, and shortness of breath. Chest computed tomography revealed numerous small, bilateral pulmonary nodules; laboratory testing revealed mean corpuscular volume, 96.1 fL; hemoglobin level, 12.4 mg/dL; and leukopenia. What is the diagnosis and what would you do next?
The Threat of Florida’s New Legislation on Undocumented Individuals—A Call for Action
Authors: Olazagasti Coral
Published: February 2024

This essay describes the author’s experience with a patient that illustrates what undocumented individuals living in Florida are experiencing due to Bill 1718.
Visual Impairment and Real-World Home Physical Activity With Home Environment in an Older Population
Authors: Banerjee Seema , Mihailovic Aleksandra , Miller Rhonda , E Jian-Yu , Gitlin Laura N. , Xiong Yingzi , West Sheila , Friedman David S. , Ramulu Pradeep Y.
Published: February 2024

Importance

Physical activity levels are lower in visual impairment. However, additional factors, such as home environmental features, which can modify physical activity in this group, are unknown.

Objective

To investigate the association between home environment features and home physical activity in patients with visual impairment.

Design, Setting, and Participants

This cross-sectional study of clinical patients included participants with glaucoma suspect and primary glaucoma who were 60 years or older with varying degrees of visual field damage. Study participants were recruited from the Johns Hopkins Wilmer Eye Institute Glaucoma Clinic, Baltimore, Maryland, from September 2013 through March 2015. Data were analyzed from December 19, 2022, through December 25, 2022.

Main Outcomes and Measures

Total in-home steps taken per day was the primary outcome measure; time in daily home physical activity and nonsedentary activity were secondary outcomes.

Results

A total of 153 participants were included in analyses with mean age of 71 (SD, 7.8) years and 71 were female (46%). Sixty percent had more than 1 comorbid illness, about one-third took 5 or more prescription drugs, and median daily home steps were 1137. Median integrated visual field sensitivity was 28 dB. Better-eye median visual acuity in logMAR was 0.05 (20/22 Snellen equivalent). For every 0.1-log unit increment in average measured home lighting, participants took 5% more daily steps (rate ratio [RR], 1.05; 95% CI, 1.00-1.10; P = .04) and had a 3% faster average daily peak cadence (RR, 1.03; 95% CI, 1.01-1.05; P = .01). The average number of nonsedentary activity minutes (RR, 1.04; 95% CI, 1.00-1.07; P = .06), average bout duration (β = 0.03; 95% CI, 0.00-.07; P = .06), and activity fragmentation (β = −0.06; 95% CI, −0.13 to 0.00; P = .06) showed associations with home lighting. The number of hazards was not associated with any activity metric (steps: RR, 1.14; 95% CI, 0.96-1.34; P = .13; peak cadence: RR, 1.00; 95% CI, 0.93-1.08; P = .98; and nonsedentary time: RR, 1.11; 95% CI, 0.98-1.26; P = .11), nor was the frequency of hazards.

Conclusions and Relevance

In this study, results demonstrated that home environment features, particularly lighting, may influence home activity metrics in older adults with visual impairment. Further prospective studies would be needed to confirm if home modifications can improve at-home activity.
Cystic-Appearing Eyelid Lesion in a 62-Year-Old Man
Authors: Feng Yilin , Chiou Carolina A. , Wolkow Natalie
Published: February 2024

A 62-year-old male was referred for evaluation of a painless right lower-eyelid lesion noted during routine glaucoma follow-up. The lesion had been present for 3 years with slow, gradual enlargement. What would you do next?
Smoking, Drinking, and Dietary Risk Factors for Head and Neck Cancer in Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Participants
Authors: Lander Daniel P. , Kallogjeri Dorina , Piccirillo Jay F.
Published: February 2024

Importance

There is a paucity of large-scale prospective studies evaluating the risk of developing head and neck cancer (HNC) associated with smoking, drinking, and dietary habits.

Objective

To determine the association of smoking, drinking, and dietary habits with the risk of developing HNC.

Design, Setting, and Participants

A nested cohort survival analysis of Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial participants was performed. Participants were between 55 and 74 years of age and recruited at 10 centers across the US from November 1993 to July 2001. Participants who developed HNC were matched with controls based on demographics and family history of HNC for analysis of smoking habits; for the analysis of drinking and dietary habits, matching was performed on smoking status and duration in addition to demographics and family history of HNC. Data analysis was performed from January to November 2023.

Exposures

Smoking, drinking, and dietary habits.

Main Outcome and Measure

Diagnosis of HNC.

Results

In total, 139 926 participants (51% female; mean [SD] age, 62.6 [5.4] years) were included in the analysis of smoking habits with a median (IQR) follow-up time of 12.1 (10.3-13.6) years, 571 of whom developed HNC. HNC risk associated with smoking increased the closer the proximity of the head and neck subsite to the lungs, with the greatest risk associated with smoking observed in laryngeal cancer (current smoker hazard ratio [HR], 9.36; 95% CI, 5.78-15.15 compared to a nonsmoker). For analysis of drinking and dietary habits, 94 466 participants were included in the analysis of smoking habits with a median (IQR) follow-up time of 12.2 (10.5-13.6) years, 264 of whom developed HNC. HNC risk increased with heavy drinking (HR, 1.85; 95% CI, 1.44-2.38) and decreased with consumption of whole grains (HR, 0.78; 95% CI, 0.64-0.94/oz per day), whole fruits (HR, 0.90; 95% CI, 0.82-0.98/cup per day), and overall healthy eating, as scored by Healthy Eating Index 2015 (HR, 0.87; 95% CI, 0.78-0.98/10 points).

Conclusions and Relevance

In this nested cohort study, the risk of HNC associated with smoking was higher for subsites that were closer to the lungs; heavy drinking was associated with greater HNC risk, while healthy eating was associated with a modest reduction in HNC risk.
Fluorogenic RNA Aptamer‐Based Amplification and Transcription Strategy for Label‐free Sensing of Methyltransferase Activity in Complex Matrixes
Authors: Gu Yu , Fan Cunxia , Yang Hongbin , Sun Huiping , Wang Xiaobao , Qiu Xingchen , Chen Bo , Li Chang‐Ming , Guo Chunxian
Published: February 2024

DNA methyltransferase is significant in cellular activities and gene expression, and its aberrant expression is closely linked to various cancers during initiation and progression. Currently, there is a great demand for reliable and label‐free techniques for DNA methyltransferase evaluation in tumor diagnosis and cancer therapy. Herein, a low‐background fluorescent RNA aptamer‐based sensing approach for label‐free quantification of cytosine‐guanine (CpG) dinucleotides methyltransferase (M.SssI) is reported. The fluorogenic light‐up RNA aptamers‐based strategy exhibits high selectivity via restriction endonuclease, padlock‐based recognition, and RNA transcription. By combining rolling circle amplification (RCA), and RNA transcription with fluorescence response of RNA aptamers of Spinach‐dye compound, the proposed platform exhibited efficiently ultrahigh sensitivity toward M.SssI. Eventually, the detection can be achieved in a linear range of 0.02–100 U mL−1 with a detection limit of 1.6 × 10−3 U mL−1. Owing to these superior features, the method is further applied in serum samples spiked M.SssI, which delivers a recovery ranging from 92.0 to 107.0% and a relative standard deviation <7.0%, providing a promising and practical tool for determining M.SssI in complex biological matrices.
Organic Catalysis Promotor for Advanced Water Electrolysis
Authors: Lee Sechan , Lee Changsoo , Kim MinJoong , Doo Gisu , Seo Myeongmin , Park Hyeonjung , Lee Yeonsoo , Yun Young Hwa , Kim Ik‐Sun , Jung Hye Bin , Cho Hyun‐Seok
Published: February 2024

Achieving carbon neutrality necessitates large‐scale water electrolyzers for green hydrogen production. Accordingly, it is emphasized to develop promising catalyst candidates, which can simultaneously achieve high catalysis efficiency, environmental friendliness, and sustainability. Recently, 3d‐transition‐metal–based catalysts are proposed to replace noble‐metal–based catalysts, which have limited reserves and emit CO2 during their production; however, the limited catalytic performance of 3d‐transition‐metal–based catalysts introduces a tradeoff. Therefore, in this work, the authors focus on suggesting a breakthrough that can intrinsically enhance the catalysis efficiency by adopting a new component in water electrolysis system. Here, a novel concept of organic catalysis promotor (OCP), dissolved in the electrolyte as an additive, which accelerates the sluggish oxygen evolution reaction in alkaline‐based water electrolysis, currently the most mature technology, is proposed. OCP acts as a liquid‐phase cocatalyst, decreasing the activation energy of oxygen evolution reaction by spontaneous chemical reduction to extract an electron from the reaction intermediates. This innovative approach of adopting the OCP of the 2,2,6,6‐tetramethylpiperidine‐1‐oxyl series significantly decreases the overpotential and shows successful general applicability, offering a new rudder in shifting the energy paradigm toward carbon neutrality.
UV‐Induced Synthesis of Graphene Supported Iridium Catalyst with Multiple Active Sites for Overall Water Splitting
Authors: Li Xu , Cao Jianyun , Chen Jiexin , Zhu Yanlei , Xia Huiqi , Xu Zifan , Gu Chengding , Xie Jiyang , Jones Mikey , Lyu Cheng , Corbin Jack , Li Xiaohong , Hu Wanbiao
Published: February 2024

Catalysts that can promote the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER) are in demand for efficient water splitting. Here, a general and practical UV‐induced synthesis of noble metal catalysts supported on reduced electrochemical graphene oxide (M‐rEGO, M = Ir, Pt or Pd) is proposed. The use of EGO with a low degree of oxidation and the generation of the highly reducing isopropanol radical from added isopropanol and acetone are crucial for this one‐step, one‐pot synthesis. Using Ir as a model material, the vacancies of rEGO allow the interaction of undercoordinated C with Ir, forming multiple active Ir species including single atoms (SAs), dual‐atom pairs (DAs) and nanoparticles. This Ir‐rEGO catalyst exhibits overpotentials of only 42.3 and 294 mV to reach 10 mA cm−2 in 0.5 м H2SO4 for HER and 1 м KOH for OER, respectively, at an extremely low Ir loading (2.1 wt%). The water‐splitting cells featuring Ir‐rEGO catalyst outperform those using commercial Pt/C (20 wt%) and RuO2 catalysts in both acidic and alkaline electrolytes. Density functional theory calculations confirm the stabilization of SAs and DAs at the vacancies of graphene lattice as well as the high activity of DAs in both HER and OER.
Self‐Powered Sweat‐Responsive Structural Color Display
Authors: Kim Taebin , Park Tae Hyun , Lee Jae Won , Lee Dongwook , Mun Seungsoo , Kim Gwangmook , Kim Yeonji , Kim Gwanho , Park Jong Woong , Lee Kyuho , Lee Seung Won , Jeon Seungbae , Ryu Du Yeol , Shim Wooyoung , Kim Jayoung , Park Cheolmin
Published: February 2024

Despite the remarkable progress in the development of sweat sensors, self‐powered sweat‐responsive sensing displays that detect sweat in electric signals with simultaneous and direct visualization of the sweat is rarely demonstrated. Here, a self‐powered sweat‐responsive structural color (SC) display enabled by ionomer‐doped block copolymer (BCP) photonic crystals (PCs) is presented. The sweat‐responsive BCP PC is developed by employing a cross‐linking single‐mobile ionomer (SMI) with mobile anions anchored to immobile polycations to a 1‐D BCP PC. The hydrophobic SMI‐doped BCP PC is mechanically robust as well as water and temperature‐resistive, exhibiting ionomer concentration‐dependent full visible SCs. Moreover, the mobile anions periodically confined in the SMI‐doped BCP PC harvest triboelectric energy, giving rise to a high‐power density of ≈0.774 Mw cm−2. Cation‐sensitive SC variation is observed in the SMI‐doped BCP PC, allowing the visualization of sweat containing various cations. A skin‐patchable self‐powered sweat‐responsive display is demonstrated in which kirigami‐patterned SMI‐doped BCP PC incorporated in the display can withstand up to 50% strain during exercise. Sweat from the exercise is visualized via SC display and measured using both ionic resistance changes and triboelectric signals. In addition, the integration of sweat sensing membrane into SMI‐doped BCP PC enables the quantification of sweat.
Conversion of Host Cell Receptor into Virus Destructor by Immunodisc to Neutralize Diverse SARS‐CoV‐2 Variants
Authors: Hwang Jaehyeon , Kim Beom Kyu , Moon Seokoh , Park Wonbeom , Kim Kyeong Won , Yoon Jeong Hyeon , Oh Hyunseok , Jung Sangwon , Park Youngseo , Kim Suhyun , Kim Misoo , Kim Soomin , Jung Younghun , Park Myungseo , Kim Jun‐Ho , Jung Sang Taek , Kim Sang Jick , Kim Yong‐Sung , Chung Woo‐Jae , Song Min‐Suk , Kweon Dae‐Hyuk
Published: February 2024

The decreasing efficacy of antiviral drugs due to viral mutations highlights the challenge of developing a single agent targeting multiple strains. Using host cell viral receptors as competitive inhibitors is promising, but their low potency and membrane‐bound nature have limited this strategy. In this study, the authors show that angiotensin‐converting enzyme 2 (ACE2) in a planar membrane patch can effectively neutralize all tested severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variants that emerged during the COVID‐19 pandemic. The ACE2‐incorporated membrane patch implemented using nanodiscs replicated the spike‐mediated membrane fusion process outside the host cell, resulting in virus lysis, extracellular RNA release, and potent antiviral activity. While neutralizing antibodies became ineffective as the SARS‐CoV‐2 evolved to better penetrate host cells the ACE2‐incorporated nanodiscs became more potent, highlighting the advantages of using receptor‐incorporated nanodiscs for antiviral purposes. ACE2‐incorporated immunodisc, an Fc fusion nanodisc developed in this study, completely protected humanized mice infected with SARS‐CoV‐2 after prolonged retention in the airways. This study demonstrates that the incorporation of viral receptors into immunodisc transforms the entry gate into a potent virucide for all current and future variants, a concept that can be extended to different viruses.
3D‐Printed Shape Memory Poly(alkylene terephthalate) Scaffolds as Cardiovascular Stents Revealing Enhanced Endothelialization
Authors: Van Daele Lenny , Chausse Victor , Parmentier Laurens , Brancart Joost , Pegueroles Marta , Van Vlierberghe Sandra , Dubruel Peter
Published: February 2024

Cardiovascular diseases are the leading cause of death and current treatments such as stents still suffer from disadvantages. Balloon expansion causes damage to the arterial wall and limited and delayed endothelialization gives rise to restenosis and thrombosis. New more performing materials that circumvent these disadvantages are required to improve the success rate of interventions. To this end, the use of a novel polymer, poly(hexamethylene terephthalate), is investigated for this application. The synthesis to obtain polymers with high molar masses up to 126.5 kg mol−1 is optimized and a thorough chemical and thermal analysis is performed. The polymers are 3D‐printed into personalized cardiovascular stents using the state‐of‐the‐art solvent‐cast direct‐writing technique, the potential of these stents to expand using their shape memory behavior is established, and it is shown that the stents are more resistant to compression than the poly(l‐lactide) benchmark. Furthermore, the polymer's hydrolytic stability is demonstrated in an accelerated degradation study of 6 months. Finally, the stents are subjected to an in vitro biological evaluation, revealing that the polymer is non‐hemolytic and supports significant endothelialization after only 7 days, demonstrating the enormous potential of these polymers to serve cardiovascular applications.
Granular Hydrogels Improve Myogenic Invasion and Repair after Volumetric Muscle Loss
Authors: Tanner Gabrielle I. , Schiltz Leia , Narra Niharika , Figueiredo Marxa L. , Qazi Taimoor H.
Published: February 2024

Skeletal muscle injuries including volumetric muscle loss (VML) lead to excessive tissue scarring and permanent functional disability. Despite its high prevalence, there is currently no effective treatment for VML. Bioengineering interventions such as biomaterials that fill the VML defect to support cell and tissue growth are a promising therapeutic strategy. However, traditional biomaterials developed for this purpose lack the pore features needed to support cell infiltration. The present study investigates for the first time, the impact of granular hydrogels on muscle repair – hypothesizing that their flowability will permit conformable filling of the defect site and their inherent porosity will support the invasion of native myogenic cells, leading to effective muscle repair. Small and large microparticle fragments are prepared from photocurable hyaluronic acid polymer via extrusion fragmentation and facile size sorting. In assembled granular hydrogels, particle size and degree of packing significantly influence pore features, rheological behavior, and injectability. Using a mouse model of VML, it is demonstrated that, in contrast to bulk hydrogels, granular hydrogels support early‐stage (satellite cell invasion) and late‐stage (myofiber regeneration) muscle repair processes. Together, these results highlight the promising potential of injectable and porous granular hydrogels in supporting endogenous repair after severe muscle injury.
Surface Crystallization Modulation toward Highly‐Oriented and Phase‐Pure 2D Perovskite Solar Cells
Authors: Chen Bin , Meng Ke , Qiao Zhi , Zhai Yufeng , Yu Runze , Fang Zhu , Yan Pu , Xiao Mingyue , Pan Li , Zheng Liya , Cao Kecheng , Chen Gang
Published: February 2024

2D perovskites have shown great potential toward stable and efficient photovoltaic devices. However, the crystal orientation and phase impurity issues of 2D perovskite films originating from the anisotropic crystal structure and specific growth mechanism have demoted their optoelectronic performances. Here, the surface crystallization modulation technique is introduced to fabricate the high‐quality 2D perovskite films with both vertical crystal orientation and high phase purity by regulating the crystallization dynamics. The solvent atmosphere condition is instituted during film processing, which promotes the formation of an oriented 2D perovskite layer in stoichiometric composition at the vapor–liquid interface and templates the subsequent film growth. The solar cells based on the optimized 2D perovskite films exhibit a power conversion efficiency of 15.04%, the record for 2D perovskites (with the perovskite slab thickness n ≤ 3 and high phase purity). The solar cells based on the highly‐oriented and phase‐pure 2D perovskite films also demonstrate excellent thermal and humidity stabilities.
Achieving Multiwavelength Optical Amplification Based on Polymer Waveguides Doped with NaYF4:Er3+, Yb3+ Nanoparticles under Commercial and Convenient Led Pumping
Authors: Lv Ziyue , Shi Xiaowu , Wang Ce , Zhang Baoping , Zhang Daming , Wang Fei , Wang Xibin , Zhou Zhaoqin , Yang Xingchen , Ying Leiying , Zhu Jiyun , Huang Yuyang , Zhang Dan
Published: February 2024

Relying on a reverse energy transfer mechanism between erbium (Er3+) and ytterbium (Yb3+) ions, optical gains at wavelengths of 1550, 980, and 1067 nm are achieved in NaYF4: Er3+, and Yb3+ nanoparticles‐doped polymer waveguides under excitation of low‐power light‐emitting diodes (LEDs) instead of 976 or 1480 nm semiconductor laser as pump sources. The optical gains at 1550, 980, and 1067 nm are demonstrated in five waveguide structures: active‐rectangular, evanescent‐field with and without an aluminium (Al) reflector, and dual‐active hybrid with and without an Al reflector. The maximum relative optical gains of 6.6, 4.0, and 3.8 dBcm−1 are realized at 1550, 1067, and 980 nm, respectively, in a 5 mm long dual‐active hybrid waveguide with cross‐section of 4 × 10 µm, and a ≈100 nm‐thick Al reflector grown under the lower cladding layer under excitation of a 395 nm LED. This work proves the feasibility of using a low‐cost LED to realize multi‐wavelength amplification in a dense wavelength‐division multiplexing system and is thus valuable for the development of complex multi‐functional photonic‐integrated‐module mixed‐band optical communication systems.
Investigating Chain‐Like Core‐Shell Ge Nanowires Coated with Carbon Nanotubes Through Atomic Simulations: Implication for Improving Binding and Mechanical Properties
Authors: Zhao Dandan , Guan Yue , Zhang Lin
Published: February 2024

Atomic simulations within the classical mechanics' formalism are used to investigate the interfacial binding between carbon nanotubes (CNTs) and germanium nanowires (GeNWs) as well as the mechanical properties of the chain‐like coreshell germanium nanowires coated with CNTs. The simulations at the atomic scale provide the effect of temperature, systems’ cross–sectional diameter, interfacial distance, applied tension loading on their binding degree, and deformation behaviors. The simulation results reveal that the spacing between CNT and nanowires as well as the interfaces formed between them directly affect the thermal stability and the degree of interfacial bonding of the systems. The coreshell GeNWs  coated with CNTs present significantly excellent mechanical properties. The Lode‐Nadai parameters and the atomic hydrostatic pressures on the atoms can be used to identify atoms’ bearing states in different regions and the stress‐transfer paths during different stages including elasticity, plasticity, and fracture of the confined systems.
Total Syntheses of Hosieines A–C
Authors: Zhang Jiayang , Yan Xu , Zhang Qing‐Bao , Wang Fang , Yang Bin , Yang Yang
Published: February 2024

The collective total syntheses of (±)‐hosieines A–C with a cage‐like tetracyclic framework have been realized, which includes the first syntheses of hosieines B‐C. The key strategy of the synthesis employs a one‐pot domino reaction that involves Cu‐catalyzed [3+2] cycloaddition, 1,6‐enone formation, and 1,6‐aza‐Michael addition forming the 5/6/6‐aza‐tricyclic skeleton. Other salient synthetic tactics comprise a challenging double bond migration and a 1,4‐aza‐Michael addition reaction to afford the tetracyclic framework.
Conjugated Microporous Polymers for Catalytic CO2 Conversion
Authors: Karatayeva Ulzhalgas , Al Siyabi Safa Ali , Brahma Narzary Basiram , Baker Benjamin C. , Faul Charl F. J.
Published: February 2024

Rising carbon dioxide (CO2) levels in the atmosphere are recognized as a threat to atmospheric stability and life. Although this greenhouse gas is being produced on a large scale, there are solutions to reduction and indeed utilization of the gas. Many of these solutions involve costly or unstable technologies, such as air‐sensitive metal–organic frameworks (MOFs) for CO2 capture or “non‐green” systems such as amine scrubbing. Conjugated microporous polymers (CMPs) represent a simpler, cheaper, and greener solution to CO2 capture and utilization. They are often easy to synthesize at scale (a one pot reaction in many cases), chemically and thermally stable (especially in comparison with their MOF and covalent organic framework (COF) counterparts, owing to their amorphous nature), and, as a result, cheap to manufacture. Furthermore, their large surface areas, tunable porous frameworks and chemical structures mean they are reported as highly efficient CO2 capture motifs. In addition, they provide a dual pathway to utilize captured CO2 via chemical conversion or electrochemical reduction into industrially valuable products. Recent studies show that all these attractive properties can be realized in metal‐free CMPs, presenting a truly green option. The promising results in these two fields of CMP applications are reviewed and explored here.
3D/4D printed versatile fibre‐based wearables for embroidery, AIE‐chemosensing, and unidirectional draining
Authors: Liu Pengchao , Chu Chengshengze , Qiu Wenqi , Cheng Lizi , Gu Jialun , Mao Zhengyi , Zhao Zheng , He Xinyuan , Liu Guo , Peng Chen , Man Kwan , Tang Ben Zhong , Lu Jian
Published: February 2024

Fibre‐based wearables for embroidery, chemosensing, and biofluid's unidirectional draining with good flexibility, tunability, and designability drive technological advance. However, synthetic polymer fibres are non‐degradable, threatening the environment and human health. Herein, we have developed versatile microfibre‐based wearables by combining many advantages in one platform of biodegradable polylactic acid (PLA) and melt electrowriting strategy. Diverse potential applications of PLA wearables are achieved by flexibly designing their printing files, components and structures. Three‐dimensional printing files are generated from two‐dimensional images to fabricate ‘embroidery‐like’ patterns. PLA/aggregation‐induced emission fluorogens (AIE) chemosensors exhibit colorimetric and fluorescent colour changes upon exposure to amine vapours. Janus PLA‐cotton textiles with a hydrophobic/hydrophilic structure could facilitate unidirectional draining of sweats which is favourable for the management of temperature and humidity on the surface of skin. The proposed platform can not only broaden the design possibilities in 3D/4D printing but also offer wide potential applications for functional wearables.
Personal journeys to and in human genetics and dysmorphology
Authors: Schwartz Charles E. , Aylsworth Arthur S. , Allanson Judith , Battaglia Agatino , Carey John C. , Curry Cynthia J. , Davies Kay E. , Eichler Evan E. , Graham John M. , Hall Bryan , Hall Judith G. , Holmes Lewis B. , Hoyme H. Eugene , Hunter Alasdair , Innis Jeffrey , Johnson John , Keppler‐Noreuil Kim M. , Leroy Jules G. , Moore Cynthia , Nelson David L. , Neri Giovanni , Opitz John M. , Picketts David , Raymond F. Lucy , Shalev Stavit Allon , Stevenson Roger E. , Stumpel Connie T. R. M. , Sutherland Grant , Viskochil David H. , Weaver David D. , Zackai Elaine H.
Published: February 2024

Genetics has become a critical component of medicine over the past five to six decades. Alongside genetics, a relatively new discipline, dysmorphology, has also begun to play an important role in providing critically important diagnoses to individuals and families. Both have become indispensable to unraveling rare diseases. Almost every medical specialty relies on individuals experienced in these specialties to provide diagnoses for patients who present themselves to other doctors. Additionally, both specialties have become reliant on molecular geneticists to identify genes associated with human disorders. Many of the medical geneticists, dysmorphologists, and molecular geneticists traveled a circuitous route before arriving at the position they occupied. The purpose of collecting the memoirs contained in this article was to convey to the reader that many of the individuals who contributed to the advancement of genetics and dysmorphology since the late 1960s/early 1970s traveled along a journey based on many chances taken, replying to the necessities they faced along the way before finding full enjoyment in the practice of medical and human genetics or dysmorphology. Additionally, and of equal importance, all exhibited an ability to evolve with their field of expertise as human genetics became human genomics with the development of novel technologies.
Cerebellar heterotopia in an 11‐year‐old child with KDM6B‐related neurodevelopmental disorder: A case report and review of the literature
Authors: Politano Davide , D'Abrusco Fulvio , Pasca Ludovica , Ferraro Francesca , Gana Simone , Garau Jessica , Zanaboni Martina Paola , Rognone Elisa , Pichiecchio Anna , Borgatti Renato , Valente Enza Maria , De Giorgis Valentina , Romaniello Romina
Published: February 2024

Heterozygous pathogenic variants in KDM6B have recently been associated to a rare neurodevelopmental disorder referred to as “Neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities” and characterized by non‐pathognomonic facial and body dysmorphisms, a wide range of neurodevelopmental and behavioral disorders and nonspecific neuroradiological findings. KDM6B encodes a histone demethylase, expressed in different tissues during development, which regulates gene expression through the modulation of chromatin accessibility by RNA polymerase. We herein describe a 11‐year‐old male patient carrying a novel de novo pathogenic variant in KDM6B exhibiting facial dysmorphisms, dysgraphia, behavioral traits relatable to oppositional defiant, autism spectrum, and attention deficit hyperactivity disorders, a single seizure episode, and a neuroimaging finding of a single cerebellar heterotopic nodule, never described to date in this genetic condition. These findings expand the phenotypic spectrum of this syndrome, highlighting the potential role for KDM6B in cerebellar development and providing valuable insights for genetic counseling.
The role and molecular mechanisms of the early growth response 3 gene in schizophrenia
Authors: He Qi , Li Ruochun , Zhong Nannan , Ma Jie , Nie Fayi , Zhang Rui
Published: February 2024

Schizophrenia is a chronic, debilitating mental illness caused by both genetic and environmental factors. Genetic factors play a major role in schizophrenia development. Early growth response 3 (EGR3) is a member of the EGR family, which is associated with schizophrenia. Accumulating studies have investigated the relationship between EGR3 and schizophrenia. However, the role of EGR3 in schizophrenia pathogenesis remains unclear. In the present review, we focus on the progress of research related to the role of EGR3 in schizophrenia, including association studies between EGR3 and schizophrenia, abnormal gene expressional analysis of EGR3 in schizophrenia, biological function studies of EGR3 in schizophrenia, the molecular regulatory mechanism of EGR3 and schizophrenia susceptibility candidate genes, and possible role of EGR3 in the immune system function in schizophrenia. In summary, EGR3 is a schizophrenia risk candidate factor and has comprehensive regulatory roles in schizophrenia pathogenesis. Further studies investigating the molecular mechanisms of EGR3 in schizophrenia are warranted for understanding the pathophysiology of this disorder as well as the development of new therapeutic strategies for the treatment and control of this disorder.
Plasma biomarkers of Alzheimer's disease in the continuum of dementia with Lewy bodies
Authors: Diaz‐Galvan Patricia , Przybelski Scott A. , Algeciras‐Schimnich Alicia , Figdore Dan J. , Lesnick Timothy G. , Schwarz Christopher G. , Senjem Matthew L. , Gunter Jeffrey L. , Jack Clifford R. , Min Paul H , Jain Manoj K. , Miyagawa Toji , Forsberg Leah K. , Fields Julie A. , Savica Rodolfo , Graff‐Radford Jonathan , Ramanan Vijay K. , Jones David T. , Botha Hugo , St Louis Erik K. , Knopman David S. , Graff‐Radford Neill R. , Ferman Tanis J. , Petersen Ronald C. , Lowe Val J. , Boeve Bradley F. , Kantarci Kejal
Published: February 2024

INTRODUCTION

Patients with dementia with Lewy bodies (DLB) may have Alzheimers disease (AD) pathology that can be detected by plasma biomarkers. Our objective was to evaluate plasma biomarkers of AD and their association with positron emission tomography (PET) biomarkers of amyloid and tau deposition in the continuum of DLB, starting from prodromal stages of the disease.

METHODS

The cohort included patients with isolated rapid eye movement (REM) sleep behavior disorder (iRBD), mild cognitive impairment with Lewy bodies (MCI‐LB), or DLB, with a concurrent blood draw and PET scans.

RESULTS

Abnormal levels of plasma glial fibrillary acidic protein (GFAP) were found at the prodromal stage of MCI‐LB in association with increased amyloid PET. Abnormal levels of plasma phosphorylated tau (p‐tau)‐181 and neurofilament light (NfL) were found at the DLB stage. Plasma p‐tau‐181 showed the highest accuracy in detecting abnormal amyloid and tau PET in patients with DLB.

DISCUSSION

The range of AD co‐pathology can be detected with plasma biomarkers in the DLB continuum, particularly with plasma p‐tau‐181 and GFAP.
NIR‐II Conjugated Electrolytes as Biomimetics of Lipid Bilayers for In Vivo Liposome Tracking
Authors: Meng Yingying , Gao Ji , Zhou Peirong , Qin Xudong , Tian Miao , Wang Xiaohui , Zhou Cheng , Li Kai , Huang Fei , Cao Yong
Published: February 2024

Liposomes serve as promising and versatile vehicles for drug delivery. Tracking these nanosized vesicles, particularly in vivo, is crucial for understanding their pharmacokinetics. This study introduces the design and synthesis of three new conjugated electrolyte (CE) molecules, which emit in the second near‐infrared window (NIR‐II), facilitating deeper tissue penetration. Additionally, these CEs, acting as biomimetics of lipid bilayers, demonstrate superior compatibility with lipid membranes compared to commonly used carbocyanine dyes like DiR. To counteract the aggregation‐caused quenching effect, CEs employ a twisted backbone, as such their fluorescence intensities can effectively enhance after a fluorophore multimerization strategy. Notably, a “passive” method was employed to integrate CEs into liposomes during the liposome formation, and membrane incorporation efficiency was significantly promoted to nearly 100%. To validate the in vivo tracking capability, the CE‐containing liposomes were functionalized with cyclic arginine‐glycine‐aspartic acid (cRGD) peptides, serving as tumor‐targeting ligands. Clear fluorescent images visualizing tumor site in living mice were captured by collecting the NIR‐II emission. Uniquely, these CEs exhibit additional emission peak in visible region, enabling in vitro subcellular analysis using routine confocal microscopy. These results underscore the potential of CEs as a new‐generation of membrane‐targeting probes to facilitate the liposome‐based medicine research.
sp3‐Rich Heterocycle Synthesis on DNA: Application to DNA‐Encoded Library Production
Authors: Gruber Felix , McDonagh Anthony W. , Rose Victoria , Hunter James , Guasch Laura , Martin Rainer E. , Geigle Stefanie N. , Britton Robert
Published: February 2024

DNA encoded library (DEL) synthesis represents a convenient means to produce, annotate and store large collections of compounds in a small volume. While DELs are well suited for drug discovery campaigns, the chemistry used in their production must be compatible with the DNA tag, which can limit compound class accessibility. As a result, most DELs are heavily populated with peptidomimetic and sp2‐rich molecules. Herein, we show that sp3‐rich mono‐ and bicyclic heterocycles can be made on DNA from ketochlorohydrin aldol products through a reductive amination and cyclization process. The resulting hydroxypyrrolidines possess structural features that are desirable for DELs and target a distinct region of pharmaceutically relevant chemical space.