bluuebunny/crossref_metadata_2025 huggingface dataset:
Rhodium(III)‐Catalyzed C7‐Spiroannulation of Indolines with Maleimides: Facile Access to Aza‐Spiromulticycles
Authors: Zhao Jinfang , Pi Chao , Wu Yangjie , Cui Xiuling
Published: February 2024

Herein, we report a chemo‐ and regioselective Rh‐catalyzed redox C7‐spiroannulation reaction of N‐benzo[d]imidazole indolines with maleimides, resulting in a series of N‐benzo[d]imidazole indoline fused azaspirocycles in up to 92% yield. The synthetic utility is demonstrated by the synthesis of highly functionalized nitrogen‐containing spiropolycyclic skeletons. The annulation reaction could also be performed with maleic esters and acrylates. The products were purified by simple filtration. The Rh catalyst can be recycled, and the reaction could be performed at gram‐scale using 0.5 mol% of catalyst, which makes this protocol potentially applicable in industry. Moreover, the efficient post‐modification of pharmaceutical molecules demonstrates its practicability.
Cold Atmospheric Plasma: An Emerging Immunomodulatory Therapy
Authors: Liu Hui , Liang Xiaoliu , Teng Minglei , Li Zhenjie , Peng Yisheng , Wang Peiyu , Chen Hu , Cheng Hongwei , Liu Gang
Published: February 2024

Cold atmospheric plasma (CAP) is a novel technology that generates a unique combination of reactive oxygen and nitrogen species (ROS/RNS), electric fields, and UV radiation. CAP has shown promise in regulating the immune system and has potential clinical applications in wound healing, cancer treatment, and infection control. This review provides an overview of the immunological regulation activity of CAP, highlighting its substantial impact on cytokines production, immune cell phagocytosis, and immune cell proliferation. CAP has also been demonstrated to have potent therapeutic effect in anti‐inflammation, wound repair, viral and bacterial infections. Furthermore, CAP has been investigated as an adjuvant therapy for tumor treatment, eliciting a robust antitumor immune response and remarkable synergistic effects in diverse combination therapies. Further research is needed to fully understand the mechanisms underlying the effects of CAP on the immune system and to optimize its clinical application.
Live Organoid Cyclic Imaging
Authors: Reynolds David E. , Sun Yusha , Wang Xin , Vallapureddy Phoebe , Lim Jianhua , Pan Menghan , Fernandez Del Castillo Andres , Carlson Jonathan C. T. , Sellmyer Mark A. , Nasrallah MacLean , Binder Zev , O'Rourke Donald M. , Ming Guo‐li , Song Hongjun , Ko Jina
Published: February 2024

Organoids are becoming increasingly relevant in biology and medicine for their physiological complexity and accuracy in modeling human disease. To fully assess their biological profile while preserving their spatial information, spatiotemporal imaging tools are warranted. While previously developed imaging techniques, such as four‐dimensional (4D) live imaging and light‐sheet imaging have yielded important clinical insights, these technologies lack the combination of cyclic and multiplexed analysis. To address these challenges, bioorthogonal click chemistry is applied to display the first demonstration of multiplexed cyclic imaging of live and fixed patient‐derived glioblastoma tumor organoids. This technology exploits bioorthogonal click chemistry to quench fluorescent signals from the surface and intracellular of labeled cells across multiple cycles, allowing for more accurate and efficient molecular profiling of their complex phenotypes. Herein, the versatility of this technology is demonstrated for the screening of glioblastoma markers in patient‐derived human glioblastoma organoids while conserving their viability. It is anticipated that the findings and applications of this work can be broadly translated into investigating physiological developments in other organoid systems.
ASTK: A Machine Learning‐Based Integrative Software for Alternative Splicing Analysis
Authors: Huang Shenghui , He Jiangshuang , Yu Lei , Guo Jun , Jiang Shangying , Sun Zhaoxia , Cheng Linghui , Chen Xing , Ji Xiang , Zhang Yi
Published: February 2024

Alternative splicing (AS) is a fundamental mechanism that regulates gene expressionin both physiological and pathological processes. This article introduces ASTK, a software package covering upstream and downstream analysis of AS. Initially, ASTK offers a module to perform enrichment analysis at both the gene‐ and exon‐level to incorporate various impacts by different spliced events on a single gene. We further cluster AS genes and alternative exons into three groups based on spliced exon sizes (micro‐, mid‐, and macro‐), which are preferentially associated with distinct biological pathways. A major challenge in the field has been decoding the regulatory codes of splicing. ASTK adeptly extracts both sequence features and epigenetic marks associated with AS events. Through the application of machine learning algorithms, we identified pivotal features influencing the inclusion levels of most AS types. Notably, the splice site strength is a primary determinant for the inclusion levels in alternative 3’/5’ splice sites (A3/A5). For the alternative first exon and skipping exon classes, a combination of sequence and epigenetic features collaboratively dictate exon inclusion/exclusion. Our findings underscore ASTK's capability to enhance the functional understanding of AS events and shed light on the intricacies of splicing regulation.
Benzylic C(sp3)−H Alkoxylation through Visible‐Light‐Driven Oxidative Radical‐Polar Crossover
Authors: Yamashita Kenji , Kawahara Fumiya , Hamashima Yoshitaka
Published: February 2024

We report a metal‐free method for benzylic C(sp3)−H alkoxylation with a silyl ether as an alkoxylating agent. The reaction is considered to proceed through a sequence consisting of hydrogen atom transfer (HAT) and oxidative radical‐polar crossover, wherein Selectfluor serves as a one‐electron oxidant, a HAT agent, and a fluoride ion source. The fluoride ion formed in situ activates the silyl ether to give the alkoxide nucleophile, which reacts with a benzyl cation intermediate to provide the benzyl ether product. The present protocol has a broad substrate scope, enabling C−H alkoxylation of primary, secondary, and tertiary benzylic C(sp3)−H bonds. Furthermore, it is applicable for late‐stage C−H alkoxylation of bioactive molecules.
Incremental value of amyloid PET in a tertiary memory clinic setting in China
Authors: Chen Ke‐Liang , Wang Ming‐Yu , Wu Jie , Zuo Chuan‐Tao , Huang Yu‐Yuan , Wang Wei‐Yi , Zhao Meng , Zhang Ya‐Ru , Zhang Xue , Chen Shu‐Fen , Liu Wei‐Shi , Li Meng‐Meng , Ge Jing‐Jie , Ma Xiao‐Xi , Wang Jie , Zheng Li , Guan Yi‐Hui , Dong Qiang , Cui Mei , Xie Fang , Zhao Qian‐Hua , Yu Jin‐Tai
Published: February 2024

INTRODUCTION

The objective of this study is to investigate the incremental value of amyloid positron emission tomography (Aβ‐PET) in a tertiary memory clinic setting in China.

METHODS

A total of 1073 patients were offered Aβ‐PET using 18F‐florbetapir. The neurologists determined a suspected etiology (Alzheimer's disease [AD] or non‐AD) with a percentage estimate of their confidence and medication prescription both before and after receiving the Aβ‐PET results.

RESULTS

After disclosure of the Aβ‐PET results, etiological diagnoses changed in 19.3% of patients, and diagnostic confidence increased from 69.3% to 85.6%. Amyloid PET results led to a change of treatment plan in 36.5% of patients. Compared to the late‐onset group, the early‐onset group had a more frequent change in diagnoses and a higher increase in diagnostic confidence.

DISCUSSION

Aβ‐PET has significant impacts on the changes of diagnoses and management in Chinese population. Early‐onset cases are more likely to benefit from Aβ‐PET than late‐onset cases.

Highlights

Amyloid PET contributes to diagnostic changes and its confidence in Chinese patients.

Amyloid PET leads to a change of treatment plans in Chinese patients.

Early‐onset cases are more likely to benefit from amyloid PET than late‐onset cases.
Characterization and Engineering of Two Highly Paralogous Sesquiterpene Synthases Reveal a Regioselective Reprotonation Switch
Authors: Ye Dan , Shao Yi‐Zhen , Li Wen‐Rui , Cui Zhen‐Jia , Gong Ting , Yang Jin‐Ling , Wang Hai‐Qiang , Dai Jun‐Gui , Feng Ke‐Ping , Ma Ming , Ma Shuang‐Gang , Liu Yun‐Bao , Zhu Ping , Yu Shi‐Shan
Published: February 2024

Sesquiterpene synthases (STPSs) catalyze carbocation‐driven cyclization reactions that can generate structurally diverse hydrocarbons. The deprotonation‐reprotonation process is widely used in STPSs to promote structural diversity, largely attributable to the distinct regio/stereoselective reprotonations. However, the molecular basis for reprotonation regioselectivity remains largely understudied. Herein, we analyzed two highly paralogous STPSs, Artabotrys hexapetalus (−)‐cyperene synthase (AhCS) and ishwarane synthase (AhIS), which catalyze reactions that are distinct from the regioselective protonation of germacrene A (GA), resulting in distinct skeletons of 5/5/6 tricyclic (−)‐cyperene and 6/6/5/3 tetracyclic ishwarane, respectively. Isotopic labeling experiments demonstrated that these protonations occur at C3 and C6 of GA in AhCS and AhIS, respectively. The cryo‐electron microscopy‐derived AhCS complex structure provided the structural basis for identifying different key active site residues that may govern their functional disparity. The structure‐guided mutagenesis of these residues resulted in successful functional interconversion between AhCS and AhIS, thus targeting the three active site residues [L311‐S419‐C458]/[M311‐V419‐A458] that may act as a C3/C6 reprotonation switch for GA. These findings facilitate the rational design or directed evolution of STPSs with structurally diverse skeletons.
Light‐Driven C−C Coupling for Targeted Synthesis of CH3COOH with Nearly 100 % Selectivity from CO2
Authors: Ding Jinyu , Du Peijin , Zhu Juncheng , Hu Qing , He Dongpo , Wu Yang , Liu Wenxiu , Zhu Shan , Yan Wensheng , Hu Jun , Zhu Junfa , Chen Qingxia , Jiao Xingchen , Xie Yi
Published: February 2024

Targeted synthesis of acetic acid (CH3COOH) from CO2 photoreduction under mild conditions mainly limits by the kinetic challenge of the C−C coupling. Herein, we utilized doping engineering to build charge‐asymmetrical metal pair sites for boosted C−C coupling, enhancing the activity and selectivity of CO2 photoreduction towards CH3COOH. As a prototype, the Pd doped Co3O4 atomic layers are synthesized, where the established charge‐asymmetrical cobalt pair sites are verified by X‐ray photoelectron spectroscopy and X‐ray absorption near edge spectroscopy spectra. Theoretical calculations not only reveal the charge‐asymmetrical cobalt pair sites caused by Pd atom doping, but also manifest the promoted C−C coupling of double *COOH intermediates through shortening of the coupled C−C bond distance from 1.54 to 1.52 Å and lowering their formation energy barrier from 0.77 to 0.33 eV. Importantly, the decreased reaction energy barrier from the protonation of two*COOH into *CO intermediates for the Pd‐Co3O4 atomic layer slab is 0.49 eV, higher than that of the Co3O4 atomic layer slab (0.41 eV). Therefore, the Pd‐Co3O4 atomic layers exhibit the CH3COOH evolution rate of ca. 13.8 μmol g−1 h−1 with near 100% selectivity, both of which outperform all previously reported single photocatalysts for CO2 photoreduction towards CH3COOH under similar conditions.
Centering dialog and care in digital Indigenous knowledge stewardship: Of relationality, responsibility, and respect
Authors: Liew Chern Li , Lipscombe Ailsa
Published: February 2024

The question of how to appropriately care for and share Indigenous knowledges is central to cultural heritage documentation and, contemporary archival praxes and discourses. Transforming the standards of Indigenous knowledge management (IKM) necessitates confronting the legacies of colonial control and Indigenous expurgation that settler colonial galleries, libraries, archives, and museums (GLAM) have contributed to (intentionally or not). Writing of and within the Māori context in New Zealand, we argue that a renewed orientation toward dialogic collaboration between institutions and Indigenous communities is crucial for revitalizing archival practices and partnerships in ways that center Indigenous values. Moreover, we purport that aligning institutional practices with Indigenous values is insufficient if Indigenous communities are neither made to feel welcome within archival spaces nor empowered to utilize them. As such, we identify the notions of relationality, responsibility, and respect as vital in supporting this ethical transformation of Indigenous knowledge stewardship both in New Zealand and in other Indigenous contexts. We propose that current efforts to reshape IKM praxes in culturally responsible and responsive ways can be meaningfully expanded through dialogic engagement, and an ethics of care.
Uptake of silicate by pipe scale materials and effects on lead release
Authors: Mishrra Anushka , Wang Ziqi , Giammar Daniel E.
Published: February 2024

The interactions between dissolved silica and corrosion scale on lead pipes such as hydrocerussite (Pb3(CO3)2(OH)2) and aluminum containing amorphous phases can affect the rates of lead release from the pipes to drinking water. Batch experiments that were well mixed to fully suspend these materials complemented previous experiments that were performed with pipes with intact pipe scales. These experiments focused on chemical interactions between the corrosion scale materials and silicate by decreasing the effect of mass transfer processes associated with solute diffusion into and out of intact scales. The findings from the batch experiments help us understand that the benefits of silicate addition in controlling lead release observed in a previous pipe loop study with pipes with intact scale were primarily due to inhibited diffusion of lead through the scale as a result of silicate uptake and not due to chemical interactions between lead‐containing solids and silicate.
Impact of Ionic Liquid Functionalized ZrO2 Nanoparticles on Poly (stearyl methacrylate) Grafted Poly (vinylidene fluoride‐co‐hexafluoropropylene) Based Highly Conductive Gel Polymer Electrolytes for Lithium‐Metal Batteries
Authors: Parui Rittik , Deb Debalina , Bose Pallab , Bhattacharya Subhratanu
Published: February 2024

In this study, an organic‐inorganic hybrid polymer membrane is successfully designed and developed by grafting stearyl methacrylate (SMA) side chains onto the backbone of the P(VDF‐HFP) copolymer followed by blending with varying amounts of imidazolium ionic liquids functionalized ZrO2 nanoparticles. Different microporous gel polymer electrolytes (MGPEs) are prepared by immersing the membranes into a LiTFSI salt‐dissolved ionic liquid electrolyte. The membranes′ crystallinity, surface morphology, porosity, and thermal stability are investigated using various characterization techniques. The copolymer membrane blended with 60 wt % functionalized nanoparticles exhibits the highest porosity of 64.5 %, which allows it to achieve a maximum electrolyte uptake of 387 wt %. That enables the corresponding MGPE to achieve the highest room temperature lithium ion conductivity of ~5.34×10−3 S cm−1 with a wide electrochemical stability window and good electrochemical stability against Li metal. Leveraging these advantageous characteristics, the lab‐scale truly solid‐state Li|MGPE|LiFePO4 and Li|MGPE|LiNi0.8Mn0.1Co0.1O2 cells demonstrate excellent rate capability and reversible cycling stability while maintaining high specific capacities (up to 154 and 172 mAh g−1, respectively, at 0.5 C) with >99.0 % coulombic efficiency over 100 cycles. Such exceptional interfacial compatibility with both low‐ and high‐voltage cathodes establishes the applicability of these newly developed MGPEs in next‐generation all‐solid‐state lithium‐metal batteries.
A rare case of traumatic head arteriovenous fistula
Authors: Shao Lifan , Cao Guangxin
Published: February 2024

Key clinical information

We report a case of traumatic scalp and dural arteriovenous fistula with significant vascular malformation, which is important for our understanding of this disease.
Diffusion Models of Mass Transport for the Characterisation of Amperometric Gas Sensors
Authors: Saunders L. , Mudashiru L. K. , Baron R. , Horrocks B. R.
Published: February 2024

A diffusion model for the analysis of chronoamperometric data in response to a concentration step is developed for amperometric gas sensors. This analysis avoids the difficulties with standard potentiodynamic measurements at the large specific area, high capacitance electrodes employed in these sensors. Despite the fact that typical devices comprise multiple layers with varying thicknesses and diffusivities, we show that typical chronoamperometric traces can be fitted to a simple diffusion model with a single parameter
where L is an overall effective thickness of the diffusion barrier and D is an effective diffusion coefficient. Through a comparison of the transient and steady‐state current, independent estimates of L and D in the devices can be made. The model is also extended to cover cases with interfacial kinetic barriers; such kinetic limitations lead to a change in the effective values L and D, but the simple diffusion model remains a good fit to the data. This analysis shows that transient sensor responses can be characterised by a single parameter τ and conversely that deviations from this regression model cannot be assigned to (i) complex layer architectures or (ii) interlayer kinetic barriers. Instead, we show that non‐uniform accessibility effects arising from a distribution of diffusion rates across the device lead to deviations from the simple regression model, but that they may be captured approximately by a more complex model in which τ has a probability distribution.
Ultrafast Halogen Dance Reactions of Bromoarenes Enabled by Catalytic Potassium Hexamethyldisilazide
Authors: Inoue Kengo , Mori Atsunori , Okano Kentaro
Published: February 2024

Lochmann–Schlosser base, a stoichiometric combination of nBuLi and KOtBu, is commonly used as a superbase for deprotonating a wide range of organic compounds. In the present study, we report that catalytic potassium hexamethyldisilazide (KHMDS) exhibits higher catalytic activity than KOtBu for successive bromine–metal exchanges. Accordingly, 1–10 mol% of KHMDS dramatically enhances halogen dance reactions to introduce various electrophiles to bromopyridine, bromoimidazole, bromothiophene, bromofuran, and bromobenzene derivatives with the bromo group translocated from the original position. A dual catalytic cycle is proposed to explain the ultrafast bromine transfer.
Trifluoromethyl Fluorosulfonate (CF3OSO2F) and Trifluoromethoxy Sulfur Pentafluoride (CF3OSF5) – Two Gaseous Sulfur(VI) Compounds with Insulating Properties
Authors: Golz Paul , Dreyhsig Gesa H. , Pernice Holger , Drews Thomas , Nissen Jan H. , Beckers Helmut , Steinhauer Simon , Wiesner Anja , Riedel Sebastian
Published: February 2024

In this work, we analyzed trifluoromethyl fluorosulfonate (CF3OSO2F) and trifluoromethoxy sulfur pentafluoride (CF3OSF5) regarding their potential use as dielectrics by investigating some of their intrinsic and extrinsic properties. Both compounds show a higher breakdown voltage than SF6 with averaged relative breakdown voltages of 1.3±0.2 for CF3OSO2F and 1.4±0.2 for CF3OSF5 compared to SF6 with 1.0. Like the dielectric (CF3)2CFCN, both compounds decompose during the breakdown process. The decomposition products were analyzed by IR spectroscopy and GCIR methods. Furthermore, the molecular structures of both gaseous compounds CF3OSO2F and CF3OSF5 have been determined by in situ crystallization, and their physical properties were determined as well.
Droplet deposition of agrochemical spraying: Comparison of results from a random‐walk model and CFD simulations
Authors: Renaudo Carlos A. , Bucalá Veronica , Bertin D. E.
Published: February 2024

The effectiveness of agricultural spraying processes depends considerably on the ability of the atomized droplets to reach the target site in the desired amount. In this work, two mathematical models to study the trajectories and deposition of atomized droplets are implemented and compared. On the one hand, a computational fluid dynamics (CFD) coupled with discrete phase model (DPM) is implemented to calculate the trajectories of atomized droplets and determine distances at which the droplets are deposited. The continuous phase (atmospheric air) is modelled by continuity, momentum, and energy equations. On the other hand, a Lagrangian random‐walk (LRW) model based on force and energy balances to predict the pulverization process of a nozzle is formulated and implemented in Python. Both models take into account the effects of drag, gravity, buoyancy, and evaporation on individual droplets, as well as the impact of atmospheric stability and dispersion. By tracking a large number of trajectories, meaningful estimates of dispersal statistics can be obtained. The LRW model accurately replicated the trajectories, deposition distances, and final diameters of atomized droplets for three atmospheric stability cases, compared with CFD simulation results. The results of both models agreed that 100 μm droplets were most susceptible to wind‐induced spray drift, depositing at the furthest distances from the nozzle. In addition, 50 μm droplets exhibited a significant tendency to evaporate entirely before reaching the ground. The LRW model is found to be a cost‐effective alternative for estimating spray drift compared to the computationally intensive CFD approach.
Rearrangement of GUV‐confined actin networks in response to micropipette aspiration
Authors: Wubshet Nadab H. , Young Cole J. , Liu Allen P.
Published: February 2024

Although diverse actin network architectures found inside the cell have been individually reconstituted outside of the cell, how different types of actin architectures reorganize under applied forces is not entirely understood. Recently, bottom‐up reconstitution has enabled studies where dynamic and phenotypic characteristics of various actin networks can be recreated in an isolated cell‐like environment. Here, by creating a giant unilamellar vesicle (GUV)‐based cell model encapsulating actin networks, we investigate how actin networks rearrange in response to localized stresses applied by micropipette aspiration. We reconstitute actin bundles and branched bundles in GUVs separately and mechanically perturb them. Interestingly, we find that, when aspirated, protrusive actin bundles that are otherwise randomly oriented in the GUV lumen collapse and align along the axis of the micropipette. However, when branched bundles are aspirated, the network remains intact and outside of the pipette while the GUV membrane is aspirated into the micropipette. These results reveal distinct responses in the rearrangement of actin networks in a network architecture‐dependent manner when subjected to physical forces.
First person profile: Michelle M. Le Beau, PhD
Authors: Nierengarten Mary Beth
Published: February 2024

This news section offers Cancer readers timely information on events, public policy analysis, topical issues, and personalities. In this issue, the life‐long fascination with cancer cytogenetics of Michelle M. Le Beau, PhD, has contributed to vast improvements in the treatment of certain cancers based on genetic subgroups. In addition, two studies show benefits for patients with resectable non‐small cell lung cancer by adding perioperative durvalumab to chemotherapy and through using amivantamab in treatment‐naive patients and in patients who experience relapse.
Urine cytology in the detection of renal cell carcinomas – a territory‐wide multi‐institutional retrospective review of more than 2 decades
Authors: Li Joshua J. X. , Ng Joanna K. M. , Tang Cheuk‐Yin , Chan Bryan C. H. , Chan Sau Yee , Law Jasmine H. N. , Teoh Jeremy Y. , VandenBussche Christopher J. , Tse Gary M.
Published: February 2024

Introduction

Compared with urothelial lesions of the upper urinary tract, the diagnostic performance of urine cytology in detection of renal cell carcinomas is underreported. This study aims to establish the role of urine cytology in the assessment of renal carcinomas by a multi‐institute review of urine cytology from nephrectomy confirmed renal cell carcinomas, referenced against renal urothelial and squamous cell carcinomas.

Methods

Records of nephrectomy performed from the 1990s to 2020s at three hospitals were retrieved and matched to urine cytology specimens collected within 1 year prior. Patient demographics, specimen descriptors, and histology and staging parameters were reviewed and compared against cytologic diagnoses.

Results

There were 1147 cases of urine cytology matched with renal cell carcinomas, with 666 renal urothelial/squamous carcinomas for comparison. The detection rate for urothelial/squamous (atypia or above [C3+]: 63.1%; suspicious or above [C4+]: 24.0%) were higher than renal cell carcinoma (C3+: 13.1%; C4+: 1.5%) (p < 0.001). The positive rate for upper tract urine exceeded other collection methods at 45.0% (C3+) and 10.0% (C4+) (p < .01). Other factors associated with increased positive rates were male sex, collecting duct carcinoma histology, nuclear grade, and renal/sinus involvement (p < .05). Multivariate analysis revealed additional positive correlations with presence of sarcomatoid tumor cells, lymphovascular invasion, and perinephric fat involvement (p < .05). Larger lesion size and higher urine volume did not improve detection rates (p < .05).

Conclusions

The detection rate of renal cell carcinomas is suboptimal compared with urothelial carcinomas, although urine samples collected from cystoscopy or percutaneous nephrostomy significantly outperformed voided urine specimens.
Prediction of lymph node status in patients with surgically treated head and neck squamous cell carcinoma via neck lavage cytology: A pilot study
Authors: Rimbach Hugo , Linxweiler Maximilian , Körner Sandrina , Smola Sigrun , Linxweiler Barbara , Speicher Stefanie , Helfrich Johanna , Solomayer Erich‐Franz , Wagner Mathias , Schick Bernhard , Kühn Jan Philipp
Published: February 2024

Background

Neck dissection is a standardized surgical procedure for patients with head and neck squamous cell carcinoma (HNSCC) and plays a critical role in the choice of adjuvant treatment based on histopathological findings. Saline irrigation is routinely performed at the end of surgery. However, this irrigant is not used for diagnostic purposes.

Methods

Intraoperative irrigation of the neck dissection wound was performed in 56 patients with HNSCC (N = 93 neck dissections), and the cytological suspension obtained was processed via the liquid‐based cytology (LBC) technique, Papanicolaou staining, and immunocytochemical staining. Microscopic preparations were screened for the presence of tumor cells and classified as positive, borderline, or negative. These results were correlated with the histopathological and clinical data.

Results

Neck lavage LBC demonstrated high diagnostic value in detecting lymph node metastases (N+) with extracapsular spread (ECS), with a specificity, sensitivity, negative predictive value, and positive predictive value of 93.1%, 100%, 100%, and 80%, respectively. Tumor cells were detected in 4.8% of N− cases, 20% of N+ cases without ECS, and 100% of N+ cases with ECS. Receiver operating characteristic curve analysis showed an area under the curve of 0.8429 for the prediction of N+ (p < .0001) and 0.9658 for the prediction of N+ with ECS (p < .0001).

Conclusions

Differential lavage cytology can provide valid and rapid information on the lymph node status in patients with HNSCC and showed an excellent correlation with histopathology. Thus, neck lavage LBC may facilitate faster and more reasonable planning of adjuvant treatment and help improve the therapeutic management of patients with HNSCC.
Safety, Tolerability, and Pharmacokinetics of Voriconazole for Injection in Two Preparations in Chinese Healthy Adult Volunteers
Authors: Yu Jin , Wu Yi , Lin Sisi , Wang Ying
Published: February 2024

Voriconazole is a second‐generation, synthetic, triazole antifungal drug based on the structure of fluconazole. We compared the safety, tolerability, and pharmacokinetic characteristics of voriconazole for injection (200 mg) manufactured by at a dose of 6 mg/kg in Chinese healthy adult volunteers. This was a single‐center, randomized, open, 2‐preparation, single‐dose, 2‐period, 2‐sequence, crossover bioequivalence clinical trial. Twenty‐four eligible, healthy, male, and female volunteers were assigned randomly to one of 2 dose‐sequence groups (test‐reference group or reference‐test group) in a 1:1 block. The voriconazole concentration in plasma was determined by protein precipitation and high‐performance liquid chromatography‐tandem mass spectrometry. The main PK parameters were calculated on the basis of a noncompartmental model. The ratio of the geometric mean of the maximum plasma drug concentration, area under the plasma concentration–time curve from time 0 to the last time of quantifiable concentration, and area under the plasma concentration‐time curve from time 0 to infinity of the test preparation, and the reference preparation was 100.4%, 102%, and 102.2%, respectively. The 90% confidence intervals were between 80% and 125%, indicating that the 2 preparations were bioequivalent. The adverse events experienced by healthy adult volunteers were mild. Both preparations had a good safety profile.
Wavily Curved Perylene Diimides: Synthesis, Characterization, and Photovoltaic Properties
Authors: Fujimoto Keisuke , Izawa Seiichiro , Yamada Kazuki , Yagi Sota , Inuzuka Toshiyasu , Sanada Kazutaka , Sakamoto Masami , Hiramoto Masahiro , Takahashi Masaki
Published: February 2024

Solubility enhancement is a key issue for developing the perylene diimide‐based functional materials. Introduction of curved structure proved an effective solubilizing method without employing steric repulsion. In this work, wavily curved perylene diimides were developed as a new family of highly soluble curved perylene diimides. Moreover, their conformational dynamics, aggregating properties, electronic properties, and photovoltaic performances were thoroughly examined in comparison to the previously reported isomer exhibiting an arched curvature. The waved isomer demonstrated heightened rigidity and a greater propensity for aggregation compared to the arched isomer, likely attributed to its more planar structure. Each benzoxepin unit played a role in cancelling out the curvature on the opposite side. While the difference in the molecular curvature did not cause significant alterations in the photophysical and electron‐accepting properties, we identified that the modulation of the curved structure is effective in controlling the morphology of the photoelectric conversion layer.
Protection‐Free, Two‐step Synthesis of C5‐C Functionalized Pyrimidine Nucleosides
Authors: Podskoczyj Karolina , Kuszczynska Anna , Dziergowska Agnieszka , Leszczynska Grazyna
Published: February 2024

A simple, reliable, and efficient method for the gram‐scale chemical synthesis of pyrimidine nucleosides functionalized with C5‐carboxyl, nitrile, ester, amide, or amidine, starting from unprotected uridine and cytidine, is described. The protocol involves the synthesis of 5‐trifluoromethyluridine and 5‐trifluoromethylcytidine with Langlois reagent (CF3SO2Na) in the presence of tert‐butyl hydroperoxide and subsequent transformation of the CF3 group to the C5‐C ‘carbon substituents’ under alkaline conditions. © 2024 Wiley Periodicals LLC.

Basic Protocol 1: Synthesis and characterization of 5‐trifluoromethyluridine (5‐CF3U) and 5‐trifluoromethylcytidine (5‐CF3C)

Basic Protocol 2: Conversion of 5‐CF3U and 5‐CF3C to several C5‐substituted ribonucleosides
Uranium Cyanides from Reactions in Liquid Ammonia Solution
Authors: Graubner Tim , Rudel Stefan S. , Ivlev Sergei I. , Karttunen Antti J. , Kraus Florian
Published: February 2024

Reactions of uranium tri‐ and tetrahalides, UBr3, UI3, UCl4, and UI4, with different cyanides MCN (M=K, Ag) in liquid anhydrous ammonia led to three novel uranium(IV) cyanide compounds. The reaction of UCl4 in the presence of KCN resulted in the compound [U(CN)(NH3)8]Cl3 ⋅ 3NH3, while UBr3 and UI3 were oxidized in the presence of AgCN to form the compounds
(μ‐CN){(H3N)5U(μ‐NH2)3U(NH3)5}]Br4 ⋅ 2NH3, and
(μ‐CN){(H3N)5U(μ‐NH2)3U(NH3)5}]I4 ⋅ 2NH3. The reaction of UI4 with KCN in aNH3 also yielded the compound
(μ‐CN){(H3N)5U(μ‐NH2)3U(NH3)5}]I4 ⋅ 2NH3. The compounds
(μ‐CN){(H3N)5U(μ‐NH2)3U(NH3)5}]X4 ⋅ 2NH3 (X=Br, I) crystallize in different space groups, Pmn21 (no. 31) and Imm2 (no. 44), respectively. In both cases, the
(μ‐CN){(H3N)5U(μ‐NH2)3U(NH3)5}]4+ cation forms infinite strands. We conducted quantum‐chemical calculations and Intrinsic Bond Orbital analyses on the observed [U(CN)(NH3)8]3+ cation and the [(μ‐CN)2{(H3N)5U(μ‐NH2)3U(NH3)5}]3+ model cation to gain insight into the bonding situation.
A matter of personality and point of view: How the interplay of reinforcement sensitivity and general attitudes towards pain impacts the responsivity to acute pain
Authors: Vetterlein A. , Hogeterp S. A. , Monzel M. , Reuter M.
Published: February 2024

Background

The relatively stable individual differences reflected in Grey's revised reinforcement sensitivity theory (rRST), with foundations in neurophysiology and learning theory, appear particularly applicable to the study of pain. However, remarkably little research has been conducted in this area. In acute pain, activation of the behavioural approach system (BAS), the behavioural inhibition system (BIS) and the fight, flight, freezing system might depend on an individual's evaluation of pain. It was thus hypothesised that higher‐order interactions of rRST traits and pain attitudes affect pain responsiveness.

Methods

To investigate relationships between rRST traits and pain attitudes and to identify patterns between clusters of participants, we conducted a study in which N = 275 healthy participants filled in Reuter and Montag's rRST‐Q and the General Attitudes Towards Pain Inventory (GATPI). Experimental (pressure, electrical, thermal) and self‐report data of pain responsiveness were collected in a subsample (N = 113).

Results

We found significant correlations between rRST‐Q and GATPI subscales of up to r = 0.34. Two clusters were identified, significantly differing in rRST‐Q and GATPI scores. Pain avoiders, characterized by high BIS, flight, freezing and negative pain attitudes, were found to be significantly more pain sensitive than pain approachers, characterized by high BAS, fight and positive pain attitudes. Moderate effects (d = 0.56 to d = 0.70) were demonstrated in subjective and objective measures and across pain modalities.

Conclusions

The present study expands the scientific knowledge on factors influencing pain responsiveness. Future research is needed to confirm implications for chronic pain prevention and therapy, particularly concerning pain avoiders.

Significance

We have identified two clusters of participants, pain avoiders and pain approachers, that not only present differential patterns of revised reinforcement theory traits and general attitudes towards pain but also differ in their pain responsiveness. Pain avoiders appeared more pain sensitive compared to pain approachers, both in objective and subjective measurements, with implications for the improvement of chronic pain prevention and therapy.
Porous carbon‐based electrochemical platform for direct electron transfer in myoglobin
Authors: Hossain Md Motaher , Morshed Jannatul , Nomoto Akira , Tsujimura Seiya , Alwarappan Subbiah
Published: February 2024

A direct electron tunneling of myoglobin (cardiac biomarker) onto a magnesium oxide templated carbon electrode surface (MgOC) was observed. The porous carbon material employed in this work possesses a 3D macropores structure. Herein, the presence of a 3D curvature‐like structure provides a favorable environment for anchoring the protein myoglobin, which facilitates direct electron transfer by the myoglobin encapsulated within electroactive carbon and improves the mass transfer inside the carbon. The direct electron transfer of myoglobin at MgOC demonstrated the usefulness of this carbon material as an effective platform for studying the redox properties of various proteins and biomolecules that are of clinical relevance. The proposed strategy is distinct from the other known electrochemical strategies that involve a denaturant to partially open up myoglobin‘s redox‐active center, and thereby myoglobin is not detected in its native state. Our results also indicated a concentration‐dependent irreversible electron transfer from the heme center to the electrode surface. Further, the detection was rapid, and the analysis can be completed within a few minutes than other existing approaches that may take a few days up to a week for the results. The MgOC electrode also exhibited excellent stability towards the detection of myoglobin.
Effects of pesticide treatment against nematode disease on soil bacterial community structure and sweet potato yield and quality
Authors: Luo Kai , Zhu Jie , Xia Boyu , Zhang Jie , Su Xiulin , Wen Haixia , Li Yuqi
Published: February 2024

Sweet potato stem nematode disease is a devastating disease, which seriously affects the yield and quality of sweet potato (Ipomoea batatas (L.) Lam.). At present, soil treatment with pesticides is mainly used to prevent sweet potato stem nematode disease. In this study, Illumina MiSeq high‐throughput sequencing technology was used to analyze the diversity of soil bacterial and fungal communities treated with different pesticides. At the same time, high performance liquid chromatography was used to determine the pesticide residues in soil and sweet potato, and the impact on sweet potato yield was investigated. Kruskal–Wallis test was used to analyze the four α‐diversity indexes of soil under different pesticide treatments, and the differences were not significant (p > 0.05), indicating that there was no significant difference in the diversity and abundance of bacterial and fungal communities in soil under different pesticide treatments. The results of principal coordinate analysis showed that there was no significant difference in bacterial and fungal community structure among different pesticide treatments (p > 0.05). Pesticide residue analysis and yield statistics of sweet potato showed that the residual amount of three kinds of pesticides in sweet potato did not exceed the maximum limit stipulated by the current National Standards for Food safety (GB2763‐2021). When 5% chlorpyrifos phoxim particles were applied at 15.18 kg/acre, sweet potato was unaffected by pests and diseases basically, and the yield was the highest.
Strengthening the Grid: Proactive Transmission Resiliency Strategies in an Era of Intensifying Storms and Climate Change
Authors: Zolton Kaitlyn , Hade Kevin
Published: February 2024

The world is changing, and so are the damages and loss of life and property from more frequent extreme weather events. Climate change is causing a steady increase in the intensity and frequency of severe storms, wildfires, and other natural disasters. Recent studies have shown an increase in electrical outage events correlated to extreme weather events from 50 per year on average in the early 2000s to over 100 annually on average during the past five years.1 These events cause substantial economic losses through infrastructure damage, manufacturing and labor disruptions, and property value losses.
Fundamental Rethinking of Supply Chain Management
Authors: Goel Soam , Pretyman David , DeCotis Paul A.
Published: February 2024

Labor disruptions, inflation, high interest rates, permitting delays, and long interconnection queues characterized the development and construction of new energy infrastructure in 2023. Terrestrial and offshore wind, solar, transmission, and hydrogen projects have been impacted most, and continued challenges are expected.
FERC Needs Court's Help on Pipelines in 2024
Authors: Makholm Jeff D.
Published: February 2024

Late in 2023, Keith Goldberg from Law360 wrote that 2024 would be a year where the courts could show the Federal Energy Regulatory Commission (FERC) the way out of its dilemma regarding how to certificate new natural gas pipelines in an era dominated by climate change exigencies. He described three cases where the courts could do so—one involving a pipeline upgrade to New York City and two others dealing with short pipelines tied to liquefied natural gas (LNG) export facilities in the U.S. Gulf Coast.1 To Goldberg, there are “signs that courts are growing impatient with the agency's continued lack of clarity on how it conducts [climate impact] reviews” tied to its pipeline certification duties. The courts need to intervene. FERC has quite evidently lost its way.
Deciphering epigenetic regulation of enhancers in high‐risk prostate cancer
Authors: Tuzova A. V. , Moran B. , Russell N. M. , Das S. , Delahaye F. , Silva R. , Barrett C. , Watson R. W. G. , O'Neill A. , Gallagher W. M. , Greally J. , Perry A. S.
Published: February 2024

Prostate cancer (PCa) is associated with widespread promoter hypermethylation. We hypothesized that aberrant DNA methylation also targets gene enhancers, modulating their activity and contributing to disease etiology. A patient discovery set (n = 37) was used for differential methylation analysis and biomarker identification using the Infinium methylation EPIC array, on high‐risk (n = 13), low‐risk (n = 11), and histologically benign (n = 13) tissues. Enhancers were primarily hypermethylated. However proportionally, hypomethylated enhancers were more prominent in high‐risk (n = 385, 15%) than low‐risk (n = 105, 10%) disease, primarily targeting genes involved in development and enriched for oncoprotein binding motifs, including FOXA1. The clinical significance of enhancer methylation was evaluated by identifying a 17 enhancer differentially methylated probe (DMP) signature using a Least Absolute Shrinkage and Selection Operator model in the discovery set. A large external dataset (n = 746) obtained from four publicly available prostate tissue methylation array studies was used to assess the enhancer signature through logistic regression models trained on a 2/3 training set and tested in a 1/3 test set. This delivered an area under the curve of 0.81 (95% bootstrapped CI 0.78–0.9) for selective detection of high‐risk PCa, achieving a 0.71 sensitivity and 0.76 specificity. Array‐wide aberrant DNA methylation at enhancers highlighted their epigenetic perturbance in high‐risk disease. A clinically significant enhancer signature from this study could be used for detecting high‐risk PCa.
Single‐nucleotide polymorphism array and fluorescence in situ hybridization analysis to decode the cytogenetic profile of atypical partial hydatidiform moles diagnosed by short tandem repeat polymorphism analysis
Authors: Suzuki Yoshiya , Usui Hirokazu , Katayama Eri , Sato Asuka , Nakamura Natsuko , Nakada Emiri , Omoto Akiko , Okayama Jun , Sato Mika , Nagasawa Akiko , Hirosawa Akiko , Shozu Makio , Koga Kaori
Published: February 2024

Accurate diagnosis of partial hydatidiform moles (PHMs) is crucial for improving outcomes of gestational trophoblastic neoplasia. The use of short tandem repeat (STR) polymorphism analysis to distinguish between PHM and hydropic abortuses is instrumental; however, its diagnostic power has not been comprehensively assessed. Herein, we evaluated the diagnostic efficacy of STR in differentiating between PHM and hydropic abortus, thus providing an opportunity for early measurement of human chorionic gonadotropin for PHMs. We reviewed charts of STR polymorphism analysis performed on fresh villous specimens and patient blood samples using a commercial kit for 16 loci. The genetic classification of 79 PHMs was confirmed. STR was reliable in differentiating PHMs when at least 15 loci were available. Typically, PHMs are characterized by their triploidy, including two paternal and one maternal haploid contribution. In our sample, seven PHMs lacked the three‐allelic loci, requiring fluorescence in situ hybridization (FISH) analysis to investigate imbalanced biparental conceptus and single‐nucleotide polymorphism array analysis to reveal cytogenetic details. Of these PHMs, two, three, and one were identified as androgenetic/biparental mosaics (diploids), monospermic diandric monogynic triploids, and a typical dispermic diandric monogynic triploid, respectively. The remaining case was monospermic origin, but its ploidy details could not be available. Therefore, STR differentiated PHM from a biparental diploid abortus in most cases. However, PHM diagnosis may be compromised when STR is used as the sole method for cases displaying distinct cytogenetic patterns lacking the three‐allelic loci, including androgenetic/biparental mosaicism. Therefore, FISH should be considered to confirm the diagnosis.
Segregation, immunohistochemical, molecular and functional analyses classify a novel missense variant in fumarate hydratase (FH) as pathogenic
Authors: Ouchene Lydia , Wilde Blake , Chan‐Pak‐Choon Fiona , Camacho Valenzuela Jose , Brimo Fadi , Witkowski Leora , Christofk Heather , Domecq Celine , Fu Lili , Weber Evan , Lemieux Anglin Brianna , Netchiporouk Elena , Foulkes William D.
Published: February 2024

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant cancer predisposition syndrome characterized by cutaneous leiomyomas, uterine leiomyomas, and aggressive renal cancer. Germline variants in the fumarate hydratase (FH) gene predispose to HLRCC. Identifying germline pathogenic FH variants enables lifetime renal cancer screening and genetic testing for family members. In this report, we present a FH missense variant (c.1039T>C (p.S347P)), initially classified as a variant of uncertain significance. Clinical assessment, histopathological findings, molecular genetic studies, and enzymatic activity studies support the re‐classification of the FH c.1039T>C variant to “pathogenic” based on ACMG/AMP criteria. Further insights into pathological recognition of FH‐deficient renal cancer are discussed and should be recognized. This study has shown how (a) detailed multi‐disciplinary analyses of a single variant can reclassify rare missense variants in FH and (b) careful pathological review of renal cancers is obligatory when HLRCC is suspected.