bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship Between Perceived In-Cabin Air Quality and Truck Drivers' Self-Reported Health and Alertness
Authors: Tay Richard , Tan Zhongchao , Cheng Xiaoying
Published: June 2011

This study surveyed 253 truck drivers and found that many drivers scored poorly on the Stanford and Epworth sleepiness scales indicating that they may not be as alert as they should be while driving. Moreover, those who rated the air in their truck cabins as fresh reported less irritation to their eyes, noses, throats, and skin, scored better in both sleepiness scales, and reported fewer sleep-related medical symptoms. Finally, the results of the ordinal logistic model indicate that drivers' perceptions of the air quality in their truck cabins are significantly related to their alertness during a trip.
Bleeding with anticoagulant treatments
Authors: Palareti G.
Published: June 2011

Anticoagulation with vitamin K antagonists (VKAs) is effective in the prevention and treatment of thrombotic complications in many clinical conditions, including atrial fibrillation (that represents today the most frequent indication for anticoagulant treatment), venous thromboembolism, acute coronary syndromes and after invasive cardiac procedures. Bleeding is the most important complication of VKAs and a major concern for both physicians and patients, limiting a more widespread prescription of the treatment. As a result, a non negligible proportion of all the subjects who would have a clear clinical indication for anticoagulation do not receive an effective treatment.

This review analyses the treatment- and person-associated risk factors for bleeding during VKAs. New oral anticoagulant drugs seems to overcome at least some of the limitations of VKAs. Potentially, they can allow a less demanding and more stable anticoagulant treatment, with less side-effects allowing that more patients can receive an appropriate anticoagulant treatment. Based on the so far available phase III clinical studies, it is possible to assume that these new drugs are associated with a risk of bleeding, that is probably related to the intensity of treatment.
Proposed CMS Data Access Changes May Hamper Health Services Research
Authors: Caplan Josh , Carroll Aaron E. , Simpson Lisa A.
Published: May 2024

This Viewpoint discusses how proposed Centers for Medicare & Medicaid Services data access changes may impede health services research.
Spirometry Interpretation After Implementation of Race-Neutral Reference Equations in Children
Authors: Forno Erick , Weiner Daniel J. , Rosas-Salazar Christian
Published: May 2024

Importance

The implications of adopting race-neutral reference equations on spirometry interpretation in children remain unknown.

Objective

To examine how spirometry results and patterns change when transitioning from Global Lung Function Initiative (GLI) race-specific reference equations (GLIR, 2012) to GLI race-neutral reference equations (GLIN, 2023).

Design, Setting, and Participants

Cross-sectional study of spirometry tests conducted in children aged 6 to 21 years between 2012 and 2022 at 2 large academic pediatric institutions in the US. Data were analyzed from September 2023 to March 2024.

Exposures

Data on participant characteristics and raw test measurements were collected. Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC z scores and percent predicted were calculated using both GLIR and GLIN. In addition, test results were categorized into normal, obstructive, suspected restrictive, mixed, suspected dysanapsis, and uncategorized patterns based on z scores calculated using GLIR or GLIN.

Main Outcomes

For each spirometry result, the difference between z scores and percent predicted when transitioning from GLIR to GLIN was calculated. The proportion of tests with a normal pattern and individual spirometry patterns changed by GLI reference equation applied were also examined.

Results

Data from 24 630 children were analyzed (mean [SD] age, 12.1 [3.8] years). There were 3848 Black children (15.6%), 19 503 White children (79.2%), and 1279 children of other races (5.2%). Following implementation of GLIN, FEV1 and FVC z scores decreased in Black children (mean difference, −0.814; 95% CI, −0.823 to −0.806; P < .001; and −0.911; 95% CI, −0.921 to −0.902; P < .001, respectively), while FEV1 and FVC z scores slightly increased (0.073; 95% CI, 0.069 to 0.076; P < .001). Similar changes were found when using percent predicted. In Black children, the number of tests with a normal pattern decreased from 2642 (68.7%) to 2383 (61.9%) (χ21 = 204.81; P < .001), mostly due to tests with a normal pattern transitioning to a suspected restrictive or uncategorized pattern. Opposite, albeit smaller, changes in spirometry results and patterns were seen in White children. In adjusted models, Black children had approximately 3-fold higher odds than White children of changing spirometry pattern following the implementation of GLIN (adjusted odds ratio, 3.15; 95% CI, 2.86 to 3.48; P < .001).

Conclusions

Pronounced differences in spirometry results and patterns were found when switching between GLI reference equations, which markedly differed by race. These findings suggest that the implementation of GLIN is likely to change the treatment of children with chronic lung diseases that are more prevalent in underrepresented minorities, such as asthma.
Tracking amyotrophic lateral sclerosis disease progression using passively collected smartphone sensor data
Authors: Karas Marta , Olsen Julia , Straczkiewicz Marcin , Johnson Stephen A. , Burke Katherine M. , Iwasaki Satoshi , Lahav Amir , Scheier Zoe A. , Clark Alison P. , Iyer Amrita S. , Huang Emily , Berry James D. , Onnela Jukka‐Pekka
Published: May 2024

Background

Passively collected smartphone sensor data provide an opportunity to study physical activity and mobility unobtrusively over long periods of time and may enable disease monitoring in people with amyotrophic lateral sclerosis (PALS).

Methods

We enrolled 63 PALS who used Beiwe mobile application that collected their smartphone accelerometer and GPS data and administered the self‐entry ALS Functional Rating Scale‐Revised (ALSFRS‐RSE) survey. We identified individual steps from accelerometer data and used the Activity Index to summarize activity at the minute level. Walking, Activity Index, and GPS outcomes were then aggregated into day‐level measures. We used linear mixed effect models (LMMs) to estimate baseline and monthly change for ALSFRS‐RSE scores (total score, subscores Q1–3, Q4–6, Q7–9, Q10–12) and smartphone sensor data measures, as well as the associations between them.

Findings

The analytic sample (N = 45) was 64.4% male with a mean age of 60.1 years. The mean observation period was 292.3 days. The ALSFRS‐RSE total score baseline mean was 35.8 and had a monthly rate of decline of −0.48 (p‐value <0.001). We observed statistically significant change over time and association with ALSFRS‐RSE total score for four smartphone sensor data‐derived measures: walking cadence from top 1 min and log‐transformed step count, step count from top 1 min, and Activity Index from top 1 min.

Interpretation

Smartphone sensors can unobtrusively track physical changes in PALS, potentially aiding disease monitoring and future research.
Preemptive dual therapy for children at risk for infantile‐onset spinal muscular atrophy
Authors: Matesanz Susan E. , Brigatti Karlla W. , Young Millie , Yum Sabrina W. , Strauss Kevin A.
Published: May 2024

Objective

Compare efficacy of gene therapy alone (monotherapy) or in combination with an SMN2 augmentation agent (dual therapy) for treatment of children at risk for spinal muscular atrophy type 1.

Methods

Eighteen newborns with biallelic SMN1 deletions and two SMN2 copies were treated preemptively with monotherapy (n = 11) or dual therapy (n = 7) and followed for a median of 3 years. Primary outcomes were independent sitting and walking. Biomarkers were serial muscle ultrasonography (efficacy) and sensory action potentials (safety).

Results

Gene therapy was administered by 7–43 postnatal days; dual therapy with risdiplam (n = 6) or nusinersen (n = 1) was started by 15–39 days. Among 18 children enrolled, 17 sat, 15 walked, and 44% had motor delay (i.e., delay or failure to achieve prespecified milestones). Those on dual therapy sat but did not walk at an earlier age. 91% of muscle ultrasounds conducted within 60 postnatal days were normal but by 3–61 months, 94% showed echogenicity and/or fasciculation of at least one muscle group; these changes were indistinguishable between monotherapy and dual therapy cohorts. Five children with three SMN2 copies were treated with monotherapy in parallel: all sat and walked on time and had normal muscle sonograms at all time points. No child on dual therapy experienced treatment‐associated adverse events. All 11 participants who completed sensory testing (including six on dual therapy) had intact sural sensory responses.

Interpretation

Preemptive dual therapy is well tolerated and may provide modest benefit for children at risk for severe spinal muscular atrophy but does not prevent widespread degenerative changes.
Field‐Effect Thermoelectric Hotspot in Monolayer Graphene Transistor
Authors: Lu Huihui , Xue Huanyi , Zeng Daobing , Liu Guanyu , Zhu Liping , Tian Ziao , Chu Paul K. , Mei Yongfeng , Zhang Miao , An Zhenghua , Di Zengfeng
Published: May 2024

Graphene is a promising candidate for the thermal management of downscaled microelectronic devices owing to its exceptional electrical and thermal properties. Nevertheless, a comprehensive understanding of the intricate electrical and thermal interconversions at a nanoscale, particularly in field‐effect transistors with prevalent gate operations, remains elusive. In this study, nanothermometric imaging is used to examine a current‐carrying monolayer graphene channel sandwiched between hexagonal boron nitride dielectrics. It is revealed for the first time that beyond the expected Joule heating, the thermoelectric Peltier effect actively plays a significant role in generating hotspots beneath the gated region. With gate‐controlled charge redistribution and a shift in the Dirac point position, an unprecedented systematic evolution of thermoelectric hotspots, underscoring their remarkable tenability is demonstrated. This study reveals the field‐effect Peltier contribution in a single graphene‐material channel of transistors, offering valuable insights into field‐effect thermoelectrics and future on‐chip energy management.
Fast Transfer of Triplet to Doublet Excitons from Organometallic Host to Organic Radical Semiconductors
Authors: Gu Qinying , Gorgon Sebastian , Romanov Alexander S. , Li Feng , Friend Richard H. , Evans Emrys W.
Published: May 2024

Spin triplet exciton formation sets limits on technologies using organic semiconductors that are confined to singlet‐triplet photophysics. In contrast, excitations in the spin doublet manifold in organic radical semiconductors can show efficient luminescence. Here the dynamics of the spin allowed process of intermolecular energy transfer from triplet to doublet excitons are explored. A carbene‐metal‐amide (CMA‐CF3) is employed as a model triplet donor host, since following photoexcitation it undergoes extremely fast intersystem crossing to generate a population of triplet excitons within 4 ps. This enables a foundational study for tracking energy transfer from triplets to a model radical semiconductor, TTM‐3PCz. Over 74% of all radical luminescence originates from the triplet channel in this system under photoexcitation. It is found that intermolecular triplet‐to‐doublet energy transfer can occur directly and rapidly, with 12% of triplet excitons transferring already on sub‐ns timescales. This enhanced triplet harvesting mechanism is utilized in efficient near‐infrared organic light‐emitting diodes, which can be extended to other opto‐electronic and ‐spintronic technologies by radical‐based spin control in molecular semiconductors.
Highly Stable and Reversible Coloration of Oxide Nanoparticles Film by Ultrafast‐CW Laser Induced Band Engineering
Authors: Hu Yifan , Lin Luchan , Wu Weiqing , Ji Junde , Zuo Xinde , Ye Jieliang , Li Hao , Shang Huan , Li Zhuguo
Published: May 2024

Coloration in oxides meets the challenge in achieving high stability and repeatability simultaneously. In this work, reversible coloration of TiO2 nanoparticles (NPs) film is demonstrated by alternate ultrafast (UF) laser and continuous wave (CW) laser irradiation. Under UF laser irradiation, oxygen vacancies are introduced in the TiO2 lattice, which lead to the bandgap reduction (2.73 to 1.50 eV) and surface blackening. The blackened area can achieve high resolution with size down to ≈1.1 µm. This coloration in TiO2 also shows excellent thermal stability that color fading is negligible even after thermal annealing at 700 K for 2 h in air. The generated high temperature by CW irradiation is known to be beneficial for the O2 dissociation on defected TiO2, thus promoting the internal oxygen diffusion to eliminate the vacancies. The energy band structure of TiO2 can be recovered accordingly, and decoloration is achieved. TiO2‐NPs film shows stable microstructures with barely changed optical properties after 12 cycles of coloration–decoloration process. This band engineering‐induced reversible coloration can also be applicable for broad oxides, e.g., ZnO, HfO2, and Ga2O3. Such highly stable and reversible coloration is promising in high‐performance micro/nano‐devices development for color display and optical encryption.
A Photoinduced Three‐Component Reaction of Thianthrenium salts, DABCO ⋅ (SO2)2, and Benzyl Ether Substituted Alkenes
Authors: Zhang Ji , Cen Jiayin , Ye Shengqing , Zheng Danqing , Wu Jie
Published: May 2024

A photoinduced three‐component reaction of thianthrenium salts, DABCO ⋅ (SO2)2, and benzyl ether substituted alkenes is developed, affording δ‐hydroxylsulfones with good functional group tolerance. This transformation proceeds through an anti‐Markovnikov hydrosulfonylation of alkenes under a mild reaction condition. Mechanism studies indicates that this reaction undergoes a radical pathway involving sulfur dioxide insertion and 1,5‐hydrogen transfer processes.
Dual Mode Ratiometric Analysis of Cu2+ and Ni2+ Ions at Physiological pH: Effect of Signalling Units on Analytical Efficacy
Authors: Dey Nilanjan , Ray Tathagata , Bhattacharya Santanu
Published: May 2024

Herein, we report the metal ion sensing property of two 2,2’‐bis (pyridylmethyl) amine‐based chromogenic probes at physiological pH in buffered media. The binding of metal ions to the bispicolyl site alters its electronic property, which subsequently influences the optical property of the covalently‐linked signaling unit. The compound experienced a change in the solution color from red to deep and light yellow respectively upon the addition of Cu2+ and Ni2+ ions. Further, it is observed that by modifying the signaling unit, one can tune the mode of metal ion binding and sensitivity. The compound with an electron‐deficient quinolinium unit as the signaling moiety, showed 2 : 1 stoichiometry of binding with metal ions, while the compound functionalized with a pyrene unit formed complexes with 1 : 1 stoichiometry. It was conferred that changes in the signaling moiety not only alter the basicity/nucleophilicity of the pyridine nitrogen ends but also influence their aggregation properties. Such kind of studies will be beneficial for engineering new optical probes with tuneable sensitivity.
XAT‐Catalysis for Intramolecular Biaryl Synthesis
Authors: Sephton Thomas , Large Jonathan M. , Natrajan Louise S. , Butterworth Sam , Greaney Michael F.
Published: May 2024

Radical ipso‐substitution offers an alternative to organometallic approaches for biaryl synthesis, but usually requires stoichiometric reagents such as tributyltin hydride. Here, we demonstrate that visible light photoredox catalysis can be used for ipso‐biaryl synthesis, via a halogen‐atom transfer (XAT) regime. Using amide substrates that promote ipso‐ over unwanted ortho‐addition, we demonstrate smooth biaryl formation with no constraint on the electronic character of the migrating arene ring. The photoreaction can be combined in one operation to achieve a formal arylation of the inert aniline C−N bond.
Static and fatigue performance of graphene nanoplatelets coated bi‐directional carbon fiber‐epoxy composites under bending loads
Authors: Srivastava Alok Kumar , Yerramalli Chandra S. , Singh Aparna
Published: May 2024

The addition of graphene nanoplatelets as a nanofiller on the surface of pristine and oxidized carbon fiber for making reinforced polymer composites has shown improvement in monotonic flexural properties. However, the fatigue response of these laminates under bending loads has not been investigated so far. The current study aims to examine the monotonic and fatigue behavior of the graphene nanoplatelets (GNPs) coated bi‐directional pristine and oxidized carbon fiber epoxy composites under bending loads. Eight layers of fabrics were used to manufacture the laminates through vacuum‐assisted resin transfer molding technique (VARTM). An optimum amount of GNP addition on oxidized fiber leads to ~830‐fold enhanced fatigue life at higher stresses as compared to pristine laminates. However, excessive GNP addition on pristine as well as oxidized fiber leads to a deterioration in fatigue life. In‐situ optical microscopic examination was done to observe the crack initiation and propagation of all the specimens with respect to the number of cycles coupled with post‐mortem SEM images of the fracture surfaces.
Disordered whiteness: A shape/an unwound sonnet late on the tide
Authors: Rao Jyoti M. , White Hazel
Published: May 2024

This paper is a multifaceted exploration of white subjectivity and the social phenomena of whiteness, about which there is a considerable body of psychoanalytic literature spanning decades. Hazel White's “unwound sonnet late on the tide” explores themes of traumatic legacies, family, shame, and mourning. Critical poetic inquiry is used to consider these themes and make links between the poetics of psychoanalytic processes and the psychoanalysis of poetics.
Local Structure and Entropic Stabilization of Ca‐Based Molten Salt Electrolytes
Authors: Timhagen Johanna , Cruz Carolina , Weidow Jonathan , Johansson Patrik
Published: May 2024

Here molten salt electrolytes (MSEs) and specifically their physico‐chemical properties as a function of composition are reported on, with a special emphasis on the compositional entropy and targeting calcium battery application. By using MSEs, several problematic issues associated with organic electrolytes, such as the blocking of Ca2+ transfer at the electrode/electrolyte interfaces and electrolyte flammability, are avoided. Ca(FSI)2 salt in combination with the analogous Li‐, Na‐, and KFSI salts are used in equimolar compositions to first create several ternary MSEs, melting at (ca.) 60–75 °C, a melting temperature which is further reduced to (ca.) 55 °C for the unique quaternary MSE. This is ascribed to an increased entropy of mixing, which also contributes to an improved stability (re−)crystallization, as shown by Raman spectroscopy. Furthermore, molecular dynamics simulations of the quaternary MSE alongside density functional theory calculations targeting the ion‐ion interactions are used to elucidate the local structure in more detail, demonstrating that both the ionic radii and valence influence the coordination and solvation of the cations. These MSEs are stepping‐stones towards completely solvent‐free, semi‐solid, and ideally room‐temperature Ca‐conducting electrolytes.
Differential protein expression and metabolite profiling in glaucoma: Insights from a multi‐omics analysis
Authors: Mok Jeong‐hun , Park Do Young , Han Jong Chul
Published: May 2024

Various substances within the aqueous humor (AH) can directly or indirectly impact intraocular tissues associated with intraocular pressure (IOP), a critical factor in glaucoma development. This study aims to investigate individual changes in these AH substances and the interactions among altered components through a multi‐omics approach. LC/MS analysis was conducted on AH samples from patients with exfoliation syndrome (XFS, n = 5), exfoliation glaucoma (XFG, n = 4), primary open‐angle glaucoma (POAG, n = 11), and cataracts (control group, n = 7). Subsequently, differentially expressed proteins and metabolites among groups, alterations in their network interactions, and their biological functions were examined. Both data‐independent acquisition and data‐dependent acquisition methods were employed to analyze the AH proteome and metabolome, and the results were integrated for a comprehensive analysis. In the proteomics analysis, proteins upregulated in both the XFG and POAG groups were associated with lipid metabolism, complement activation, and extracellular matrix regulation. Metabolomic analysis highlighted significant changes in amino acids related to antioxidant processes in the glaucoma groups. Notably, VTN, APOA1, C6, and L‐phenylalanine exhibited significant alterations in the glaucoma groups. Integration of individual omics analyses demonstrated that substances associated with inflammation and lipid metabolism, altered in the glaucoma groups, showed robust interactions within a complex network involving PLG, APOA1, and L‐phenylalanine or C3, APOD, and L‐valine. These findings offer valuable insights into the molecular mechanisms governing IOP regulation and may contribute to the development of new biomarkers for managing glaucoma.
Redox reactivity of LMCT and MLCT excited states of Earth‐abundant metal complexes
Authors: Nam Wonwoo , Lee Yong‐Min , Fukuzumi Shunichi
Published: May 2024

Precious metal complexes, which act as excellent photoredox catalysts, have now being replaced by earth‐abundant metal complexes. This review focused on redox reactivity of ligand‐to‐metal charge transfer (LMCT) and metal‐to‐ligand charge transfer (MLCT) excited states of earth‐abundant metal complexes. Iron complexes with strongly σ‐donating NHC‐ligands (NHC = N‐heterocyclic carbene) has emerged, featuring long lived LMCT excited states due to a significantly increased barrier for deactivation via metal centered states. A Fe(III)‐NHC complex acts as an effective photoredox catalyst for various photocatalytic redox reactions. Although manganese(IV)‐oxo complexes have no long‐lived excited states (τ < < 1 ns). Once acids such as Sc(OTf)3 and HOTf are bound to the oxo moiety of Mn(IV)‐oxo complexes, the photoexcitation of acid‐bound Mn(IV)‐oxo complexes resulted in formation of the excited states with microseconds lifetimes, which are capable of oxidation of substrates including benzene to phenol. Photoexcited states of Mn(III), Mn(II) and Mn(I) complexes act as photoreductants to reduce substrates including O2. On the other hand, photoexcited states of Co(IV) and Co(III) complexes act as photooxidants, whereas those of Co(II) and Co(I) complexes act as photoreductants. With regard to the excited state lifetime, [Cr(tpe)2]3+ (tpe = 1,1,1‐tris(pyrid‐2‐yl)ethane) exhibited the longest luminescence lifetime (τ = 4500 μs), acting as an effective photoredox catalyst for photocatalytic redox reactions. The LMCT state of a Cr(0) complex acts as a super photoreductant. Thus, LMCT and MLCT excited states of earth‐abundant metal complexes are utilized as strong photooxidants and photoreductants, respectively.
The impact of research and development internationalisation on environmental, social and governance: Evidence from emerging market multinational enterprises
Authors: Li Qianqiang , Li Jing , Luo Yiru
Published: May 2024

People are increasingly aware of the extent to which enterprises either improve or harm social welfare, with a growing trend to use environmental, social and governance (ESG) indicators to evaluate and describe efforts in this area. However, most research has neglected multinational enterprises, especially the significant impact of the radical and leapfrogging internationalisation of emerging market multinational enterprises (EMNEs) on sustainable development. This study discusses ESG in the context of the research and development (R&D) internationalisation of EMNEs and uses microdata from Chinese listed manufacturing enterprises from 2010 to 2020. Employing a propensity score matching (PSM) method and difference‐in‐differences (DID) estimation, this study empirically tests the effect of R&D internationalisation on the ESG performance of Chinese enterprises and their boundary conditions. This study finds that R&D internationalisation positively impacts enterprises' ESG performance through two pathways: improving green innovation and the quality of information disclosure. Furthermore, the study confirms the heterogeneous effects of institutional factors. Institutional deficits between home and host countries, along with the nature of private equity in enterprises, effectively enhance the value of the internationalisation of R&D for EMNEs on ESG performance. This study expands the exploration of the antecedents of ESG in the context of internationalisation, enriches the research on the impact effect and boundary conditions of EMNEs' R&D internationalisation and provides practical insights for EMNEs to enhance their ESG through R&D internationalisation.
Novel non‐invasive molecular signatures for oral cavity cancer, by whole transcriptome and small non‐coding RNA sequencing analyses: Predicted association with PI3K/AKT/mTOR pathway
Authors: Vageli Dimitra P. , Doukas Panagiotis G. , Townsend Jeffrey P. , Pickering Curtis , Judson Benjamin L.
Published: May 2024

Introduction

Identification of molecular biomarkers in the saliva and serum of oral cavity cancer patients represents a first step in the development of essential and efficient clinical tools for early detection and post‐treatment monitoring. We hypothesized that molecular analyses of paired saliva and serum samples from an individual would likely yield better results than analyses of either serum or saliva alone.

Materials and Methods

We performed whole‐transcriptome and small non‐coding RNA sequencing analyses on 32 samples of saliva and serum collected from the same patients with oral squamous cell carcinoma (OSCC) and healthy controls (HC).

Results

We identified 12 novel saliva and serum miRNAs and a panel of unique miRNA and mRNA signatures, significantly differentially expressed in OSCC patients relative to HC (log2 fold change: 2.6–26.8; DE: 0.02–0.000001). We utilized a combined panel of the 10 top‐deregulated miRNAs and mRNAs and evaluated their putative diagnostic potential (>87% sensitivity; 100% specificity), recommending seven of them for further validation. We also identified unique saliva and serum miRNAs associated with OSCC and smoking history (OSCC smokers vs. never‐smokers or HC: log2 fold change: 22–23; DE: 0.00003–0.000000001). Functional and pathway analyses indicated interactions between the discovered OSCC‐related non‐invasive miRNAs and mRNAs and their targets, through PI3K/AKT/mTOR signaling.

Conclusion

Our data support our hypothesis that using paired saliva and serum from the same individuals and deep sequencing analyses can provide unique combined mRNA and miRNA signatures associated with canonical pathways that may have a diagnostic advantage relative to saliva or serum alone and may be useful for clinical testing. We believe this data will contribute to effective preventive care by post‐treatment monitoring of patients, as well as suggesting potential targets for therapeutic approaches.
Natural Compound‐Rhein and PROTACs Unleash Potent VEGFR‐2 Degraders
Authors: Zhang Ziqing , Xu Meng , Shi Ruling , He Xinyi , Wang Yan , Shao Yongying , Huang Caixia , Zhang Fengyang , Zhang Peixi , Liu Jieqing
Published: May 2024

VEGFR‐2 is a prominent therapeutic target in antitumor drug research to block tumor angiogenesis. This study focused on the synthesis and optimization of PROTACs based on the natural product rhein, resulting in the successful synthesis of 15 distinct molecules. In A549 cells, D9 exhibited remarkable antitumor efficacy with an IC50 of 5.88±0.50 μM, which was 15‐fold higher compared to rhein (IC50=88.45±2.77 μM). An in‐depth study of the effect of D9 on the degradation of VEGFR‐2 revealed that D9 was able to induce the degradation of VEGFR‐2 in A549 cells in a time‐dependent manner. The observed effect was reversible, contingent upon the proteasome and ubiquitination system, and demonstrably linked to CRBN. Further experiments revealed that D9 induced apoptosis in A549 cells and led to cell cycle arrest in the G1 phase. Molecular docking simulations validated the binding mode of D9 to VEGFR, establishing the potential of D9 to bind to VEGFR‐2 in its natural state. In summary, this study confirms the feasibility of natural product‐bound PROTAC technology for the development of a new generation of VEGFR‐2 degraders, offering a novel trajectory for the future development of pharmacological agents targeting VEGFR‐2.
Computational Insights into Chromene/pyran Derivatives: Molecular Docking, ADMET Studies, DFT Calculations, and MD Simulations as Promising Candidates for Parkinson's Disease
Authors: Rani Anjali , Aslam Mohd. , Khan Javed , Pandey Garima , Singh Prashant , Maharia R. S. , Nand Bhaskara
Published: May 2024

Parkinson′s disease (PD) is a neurodegenerative condition characterized by both motor and non‐motor symptoms. Although PD is commonly associated with a decline of dopaminergic neurons in the substantia nigra, other diagnostic criteria and biomarkers also exist. In the search for novel therapeutic agents, chromene and pyran derivatives have shown potential due to their diverse pharmacological activities. This study utilizes a comprehensive computational approach to investigate the viability of chromene/pyran compounds as potential treatments for PD. The drug‐likeness characteristics of these molecules were analyzed using ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) studies. Molecular docking was performed against PDB ID: 2V5Z. The best three molecules chosen were compound 7, compound 24, and compound 67 have a binding energy of −6.7, −8.6, and −10.9 kcal/mol. Molecules demonstrating positive blood‐brain barrier permeability, good solubility, and favorable binding affinity were further evaluated using Density Functional Theory (DFT) calculations and Molecular Dynamics (MD) simulations to assess their electronic structure and stability. DFT calculations indicated that molecule 82 has a dipole moment of 15.70 D. RMSD and RMSF results confirmed the stability of the complexes over a 100 ns simulation, with a maximum of 3 hydrogen bonds formed.
A Bayesian network for estimating hypertension risk due to occupational aluminum exposure
Authors: Zhao Le , Yin Jinzhu , Huan Jiaping , Han Xiao , Zhao Dan , Song Jing , Wang Linping , Zhang Huifang , Pan Baolong , Niu Qiao , Lu Xiaoting
Published: May 2024

Background

The correlation between metals and hypertension, such as sodium, zinc, potassium, and magnesium, has been confirmed, while the relationship between aluminum and hypertension is not very clear. This study aimed to evaluate the correlation between plasma aluminum and hypertension in electrolytic aluminum workers by the Bayesian networks (BN).

Methods

In 2019, 476 male workers in an aluminum factory were investigated. The plasma aluminum concentration of workers was measured by inductively coupled plasma mass spectrometry. The influencing factors on the prevalence of hypertension were analyzed by the BN.

Results

The prevalence of hypertension was 23.9% in 476 male workers. The risk of hypertension from plasma aluminum in the Q2, Q3, and Q4 groups was 5.20 (1.90–14.25), 6.92 (2.51–19.08), and 7.33 (2.69–20.01), respectively, compared with that in the Q1 group. The risk of hypertension from the duration of exposure to aluminum of >10 years was 2.23 (1.09–4.57), compared without aluminum exposure. Area under the curve was 0.80 of plasma aluminum and the duration of exposure to aluminum was based on covariates, indicating that aluminum exposure had important predictive value in the prevalence of hypertension in the occupational population. The results of the study using the BN model showed that if the plasma aluminum of all participants was higher than Q4 (≥47.86 µg/L) and the participants were drinking, smoking, diabetes, central obesity, dyslipidemia, and aged >50 years, the proportion of hypertension was 71.2%.

Conclusions

The prevalence of hypertension increased significantly with the increase of plasma aluminum level.
Trends in the prevalence and incidence of chronic obstructive pulmonary disease among adults aged ≥50 years in the United States, 2000–2020
Authors: Meng Yaxian , Ji Qianqian , Zhang Aijie , Zhan Yiqiang
Published: May 2024

Background

Understanding the trends of the prevalence and incidence rate of chronic obstructive pulmonary disease (COPD) is vital for improving the control and prevention of COPD. We aimed to examine the trends in the prevalence and incidence rate of COPD among adults aged 50 years or older in the United States during 2000–2020.

Methods

Utilizing data from the Health and Retirement Study, we analyzed COPD prevalence across survey waves and calculated COPD incidence rates between consecutive interview waves, stratified by gender and race. We employed joinpoint regression models to investigate trends in COPD prevalence and incidence.

Results

The individuals reporting COPD are more likely to be women and Caucasians. The age‐adjusted prevalence of COPD among adults aged 50 years and over showed an increasing trend throughout the study period, spanning from 9.02% in 2000 to 9.88% in 2020 (average biennial percent change [ABPC] = 0.41, 95% confidence interval [CI]: 0.10, 0.71; p = 0.01). The age‐adjusted incidence rate of COPD among adults aged 50 and over showed a decreasing trend throughout the study period 1031.1 per 100,000 person‐years in 2000 to 700.5 per 100,000 person‐years in 2020 (ABPC = −1.63, 95% CI: −2.88, −0.36; p = 0.02).

Conclusion

Our findings indicate a rising prevalence of COPD among older adults in the United States since 2000, while the incidence rate of COPD has shown a declining trend.
Weed control and water‐seeded rice response to pyraclonil applied at different timings and in herbicide combinations
Authors: Becerra‐Alvarez Aaron , Marsh Sarah L. , Ceseski Alex R. , Al‐Khatib Kassim
Published: May 2024

Pyraclonil is a new herbicide to control weeds in California water‐seeded rice (Oryza sativa L.). The objectives of this research were to evaluate weed control and rice response from pyraclonil applied alone at different timings and when applied in combinations with other herbicides. In one field study, pyaclonil was applied at 0.3 lbs a.i. ac−1 on pre‐seed bare ground, 1‐inch flood, 4‐inch flood and 3 days after flooding in water‐seeded rice. In another study, pyraclonil was applied at 0.3 lbs a.i. ac−1 at day of rice seeding and followed by various registered herbicides. Pyraclonil applications resulted in similar weed control across timings. Pyraclonil provided greater than 92% control of smallflower umbrella sedge (Cyperus difformis L.) and broadleaf weeds but less than 60% control of ricefield bulrush [Schoenoplectus mucronatus (L.) Palla] at 42 days after treatment. Watergrass (Echinochloa spp.) control was achieved with pyraclonil if applied before emergence. Early‐season rice injury from pyraclonil was observed; however, rice appeared uninjured later in the season. The addition of other herbicides after a pyraclonil application increased weed control levels across weed species and resulted in grain yields from 6,925 to 8,623 and 9,182 to 10,865 lbs ac−1 in 2019 and 2021, respectively. Pyraclonil provides early‐season weed control and, when incorporated with other herbicides, will be a useful herbicide in water‐seeded rice.
A Macrocyclic Tweezers‐Shaped Receptor for the Biomimetic Recognition of the Gal(α1‐3)Gal Disaccharide of the α‐Gal Antigen
Authors: Milanesi Francesco , Burrini Nastassja , Corti Giona , Roelens Stefano , Francesconi Oscar
Published: May 2024

The Gal(α1‐3)Gal is the terminal disaccharide unit of the α‐Gal epitope [Gal(α1‐3)Gal(β1‐4)GlcNAc], an exogenous antigenic determinant with several clinical implications, found in all non‐primate mammals and in several dangerous pathogens, including certain protozoa and mycobacteria. Its absence in humans makes the α‐Gal epitope an interesting target for several infectious diseases. Here we present the development of a macrocyclic tweezers‐shaped receptor, resulting from the combination of the structural features of two predecessors belonging to the family of diaminocarbazole receptors, which exhibits binding properties in the low millimolar range toward the Gal(α1‐3)Gal disaccharide of the α‐Gal antigen.
Synthesis of Asymmetric Ionic Hybrid Detergents enables Micelles with Scalable Properties including Cell Compatibility
Authors: Wycisk Virginia , Behnke Jan‐Simon , Nielinger Lena , Seewald Marc , Weisner Jörn , Binsch Markus , Wagner Marc‐Christian , Raisch Tobias , Urner Leonhard H.
Published: May 2024

Ionic detergents enable applications and cause harm in biospheres due to cell toxicity. The utility of covalent combinations between ionic and non‐ionic detergent headgroups in modulating cell toxicity remains speculative due to the yet rarely explored synthesis. We close this gap and establish the modular synthesis of ionic/non‐ionic hybrid detergents. We restructure a combinatorial methallyl dichloride one‐pot coupling into a two‐step coupling, which reduces by‐products, improves product yields, and enables the gram‐scale preparation of asymmetric, cationic/non‐ionic and anionic/non‐ionic hybrid detergents. Our modular synthesis delivers new modalities for the design of ionic detergents, including an unprecedented scaling of properties that determine applications, such as charge, critical micelle concentration, solubilizing properties, hard water tolerance, and cell compatibility. We uncover that shielding the charge in ionic headgroups can switch the detergent species that is toxic to cells from monomers to mixtures of monomers and micellar assemblies. Establishing the chemistry of ionic/non‐ionic hybrid detergents provides a missing evolutionary link in the structural comparison of ionic and non‐ionic detergents, enables an easy synthesis access to yet unexplored chemical spaces of asymmetric hybrid materials, and delivers new modalities for designing the toxicity of supramolecular nanomaterials.
Facile Synthesis of Silanol Group Rich Sn‐Beta for Highly Efficient Isomerization of Glucose to Fructose
Authors: Li Meng , Lu Tianliang , Zhou Shengqiang , Zhou Lipeng , Yang Xiaomei
Published: May 2024

The isomerization of glucose to fructose is an important process in the conversion of biomass into valuable fuels and chemicals. Development of efficient catalyst for this reaction has attracted much attention. In this study, Sn‐Beta zeolites with rich silanols were synthesized for glucose isomerization by solid‐state ion‐exchange method, where Si‐Beta zeolites with different amounts of silanols were applied as the precursors. It is confirmed that open Sn sites show much higher catalytic performance than closed Sn sites for glucose isomerization (about 2.1 times). The silanol amount in Si‐Beta not only affects the formation of framework Sn sites in Sn‐Beta but also influences the isomerization reaction. More silanols in the catalyst can promote the 1,2‐H shift in isomerization and reduce the side reactions of formation of mannose and C3 products. Over 3Sn‐Beta‐3h with rich silanols, 64 % of fructose yield was obtained. Furthermore, the prepared Sn‐Beta catalyst is stable and recyclable. High fructose yield and facile synthesis method of Sn‐Beta reported in this work will contribute to the development of biomass and sugar industry.
Evaluating integration and performance of containerized climate applications on a Hewlett Packard Enterprise Cray system
Authors: Abraham Subil , Prout Ryan , Robinson Thomas , Blanton Chris , Davis Matthew
Published: May 2024

Containers have taken over large swaths of cloud computing as the most convenient way of packaging and deploying applications. The features that containers offer for packaging and deploying applications translate to high performance computing (HPC) as well. At The National Oceanic and Atmospheric Administration, containers provide an easy way to build and distribute complex HPC applications, allowing faster collaboration, portability, and experiment computer environment reproducibility amongst the scientific community. The challenge arises when applications rely on message passing interface (MPI). This necessitates investigation into how to properly run these applications with their own unique requirements and produce performance on par with native runs. We investigate the MPI performance for benchmarks and containerized climate models for various containers covering selection of compiler and MPI library combinations from the Cray provided programming environments on the Cray XC supercomputer GAEA. Performance from the benchmarks and the climate models shows that for the most part containerized applications perform on par with the natively built applications when the system optimized Cray MPICH libraries are bound into the container, and the hybrid model containers have poor performance in comparison. We also describe several challenges and our solutions in running these containers, particularly challenges with heterogeneous jobs for the containerized model runs.
Direct Comparison of the Effectiveness and Safety Among Direct Oral Anticoagulants and Warfarin in Japanese Patients: Nationwide Cohort Study in Japan
Authors: Katayama Saki , Aoki Yuka , Akita Ayu , Satake Rino , Tohkin Masahiro
Published: May 2024

Direct oral anticoagulant drugs (DOACs) are available in addition to warfarin for the treatment of patients with non‐valvular atrial fibrillation (NVAF). Anticoagulants are useful for practical pharmacotherapy in Asian populations, but their responses are different from those in Caucasian populations. Therefore, we aimed to identify the most useful anticoagulant using a nationwide insurance claims database in Japan. We extracted information on patients with NVAF treated with DOACs or warfarin for the first time between September 2015 and February 2018 to conduct a retrospective observational cohort study using the claims database of Japan. We calculated hazard ratios (HR) of effectiveness and safety endpoints among DOACs or warfarin after adjusting for backgrounds by propensity scores (inverse probability weighting). Using negative control outcomes, we considered renal function as an unmeasured confounding factor. After adjusting for their backgrounds, patients treated with DOACs showed higher effectiveness endpoints (stroke or systemic embolism) than those treated with warfarin (HR; 0.72–0.81) and higher safety in terms of safety end points (clinically significant bleeding) (HR; 0.80–0.88). The net clinical benefit, which reflects the actual clinical usefulness, indicates the advantages of DOACs over warfarin (HR; 0.75–0.82). Dabigatran had lower usefulness than edoxaban and rivaroxaban in Japanese patients treated with NVAF, even after considering the unmeasured confounding factor of kidney function. Based on practical clinical data, edoxaban and rivaroxaban were the most useful anticoagulants in Japanese patients with NVAF.
Green bonds and environmental performance: The effect of management attention
Authors: Ordonez‐Borrallo Ruben , Ortiz‐de‐Mandojana Natalia , Delgado‐Ceballos Javier
Published: May 2024

Green bonds have attracted significant interest in the business and financial sectors, yet the environmental performance outcomes among issuing firms have been uneven. Drawing on the attention‐based view framework, this study examines the role of corporate green bond issuance in directing attention to environmental issues across organizational levels. Additionally, we investigate how internal conditions, such as growth, profitability, and indebtedness, influence the translation of attention into improved environmental performance. Using a matched sample of 160 paired firms from 23 countries and nine sectors, our results emphasize the significance of both green bond intensity and internal conditions in shaping how green bonds impact environmental performance. These results contribute to the fields of sustainable finance and attention‐based view theory, offering new insights into the influence of green bonds on firms' environmental performance.
II‐Scheme Heterojunction Frameworks Based on Covalent Organic Frameworks and HKUST‐1 for Boosting Photocatalytic Hydrogen Evolution
Authors: Ma Tiantian , Liu Zhijie , Deng Jiaqi , Han Enshan , Liang Jun , Wang Ruihu
Published: May 2024

Covalent organic frameworks (COFs) are one type of promising polymer semiconductors in solar‐driven hydrogen production, but majority of COFs‐based photocatalytic systems show low photocatalytic efficiency owing to lack of metal active sites. Herein, we reported II‐Scheme heterojunction frameworks based on COF (TpPa‐1) and metal‐organic framework (HKUST‐1) for highly efficient hydrogen production. The coordination bonding directed self‐assembly of HKUST‐1 on the surface of TpPa‐1 endows the heterojunction frameworks (HKUST‐1/TpPa‐1) with strong interface interaction, optimized electronic structures and abundant redox active sites, thus remarkably boosting photocatalytic hydrogen evolution. The hydrogen evolution rate for optimal HKUST‐1/TpPa‐1 is as high as 10.50 mmol g−1 h−1, which is significantly enhanced when compared with that of their physical mixture (4.13 mmol g−1 h−1), TpPa‐1 (0.013 mmol g−1 h−1) and Pt‐based counterpart (6.70 mmol g−1 h−1). This work offers a facile approach to the construction of noble‐metal‐free II‐Scheme heterojunctions based on framework materials for efficient solar energy conversion.
Synthetic abnormal mast cell particles successfully mimic neoplastic mast cells by flow cytometry
Authors: Davis Patricia M. , Ravkov Eugene , de Geus Martina , Clauss Zach , Lee John , Nguyen Anh Tuan , Hartmann Marsha , Kim Jeffrey , George Tracy I. , Lin Leo , Ng David P.
Published: May 2024

Clinical flow cytometry laboratories require quality control materials for assay development, validation, and performance monitoring, including new reagent lot qualification. However, finding suitable controls for populations with uncommonly expressed antigens or for rare populations, such as mast cells, can be difficult. To that end, we evaluated synthetic abnormal mast cell particles (SAMCP), developed together with, and manufactured by, Slingshot Biosciences. The SAMCP's were designed to phenotypically mimic abnormal neoplastic mast cells: they were customized to have the same light scatter and autofluorescence properties of mast cells, along with surface antigen levels of CD45, CD33, CD117, CD2, CD25, and CD30 consistent with that seen in mast cell disease. We evaluated several performance characteristics of these particles using ARUP's high sensitivity clinical mast cell assay, including limit of detection, off‐target activity and FMO controls, precision, scatter properties of the particles utilizing several different cytometer platforms, and particle antigen stability. The phenotype of the SAMCP mimicked abnormal mast cells, and they could be distinguished from normal native mast cells. FMO controls demonstrated specificity of each of the markers, and no off‐target binding was detected. The limit of detection of the particles spiked into normal bone marrow was found to be ≤0.003% in a limiting dilution assay. The mast cell particles were found to perform similarly on Becton Dickinson Lyric, Cytek Aurora, and Beckman Coulter Navios and CytoFLEX platforms. Within run and between run precision were less than 10% CV. SAMCP were stable up to 13 days with minimal loss of antigen fluorescence intensity. The SAMCP's were able to successfully mimic neoplastic mast cells based on the results of our high sensitivity mast cell flow cytometry panel. These synthetic cell particles represent an exciting and innovative technology, which can fulfill vital needs in clinical flow cytometry such as serving as standardized control materials for assay development and performance monitoring.