bluuebunny/crossref_metadata_2025 huggingface dataset:
Oral Everolimus Following Dilation in Idiopathic Subglottic Stenosis
Authors: So Raymond J. , Collins Samuel L. , Collins Sarah , Mafla Laura , Chan-Li Yee , Lina Ioan , Gelbard Alexander , Motz Kevin M. , Hillel Alexander T.
Published: September 2024

Importance

Current medical therapies in idiopathic subglottic stenosis (iSGS) are insufficient in preventing the development and progression of scar tissue. An inhibitor of mammalian target of rapamycin, everolimus is an immunosuppressive medication shown to be effective in reducing fibrosis across a variety of fibroproliferative disorders, including preclinical models of iSGS.

Objective

To evaluate the effect of oral everolimus on postoperative recurrence of stenosis in iSGS.

Design, Setting, and Participants

This open-label, single-arm, phase 1, nonrandomized clinical trial analyzed 7 perimenopausal participants diagnosed with iSGS and followed-up at a tertiary care academic center for 6 months after dilation surgery. The trial was conducted from November 1, 2022, through May 15, 2024.

Intervention

Participants took a 1.5-mg daily oral dose of everolimus for 42 days after surgery.

Main outcomes and measures

The primary outcome measure was safety as determined by adverse events. Secondary outcome measures included change in peak expiratory flow from baseline through 180 days after surgery; change in the luminal area, measured by computed tomographic (CT) scan, from the 14th and the 180th day; and changes in quality-of-life scores.

Results

Of the 8 perimenopausal participants, 7 (median age, 50 years [IQR, 45.0-52.5 years]) completed the study. Compared with baseline at all time points, there was an increase in peak expiratory flow. The median difference in liters per minute was 125 (95% CI, 90-270) on day 7 after surgery; 150 (95% CI, 110-290) on day 14; 138 (95% CI, 116-280) on day 28; 160 (95% CI, 100-270) on day 42; 155 (95% CI, 110-270) on day 60; 140 (95% CI, 100-270) on day 90; and 100 (95% CI, 20-240) on day 180. A decrease in the CT luminal area was observed from the day-14 measure to the day-180 measure (median stenosis, 7.2%; IQR, 1.9%-15.4%). During the trial, 1 participant (14.3%) each developed oral ulcers, a urinary tract infection, and a skin infection.

Conclusions and Relevance

In this interventional nonrandomized clinical trial of iSGS, adjuvant everolimus was well-tolerated with minor adverse events. Participants sustained postdilation peak expiratory flow for 13 weeks. These results support proceeding to a phase 2 trial to study drug efficacy and a more detailed investigation of adverse effects.

Trial Registration

ClinicalTrials.gov Identifier: NCT05153668
Molecular and mechanical mechanisms of animal cell abscission
Authors: Öztop Amber , Chaigne Agathe
Published: September 2024

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Anomalous Temperature Effect on the Deposition Morphology in Reactive Inkjet Printing
Authors: Sreenivasan Narayanan Sreenivasan , Bender Tyler , Kanungo Mandakini , Zhao Hong
Published: September 2024

Reactive inkjet (RIJ) printing represents an important approach for printed electronics. Different from the traditional inkjet printing of colloidal inks with nanosized metal particles, RIJ prints the solution of metal organic compound, that is, metal‐organic decomposition (MOD) ink, and reduces it to the pure metal during the post‐treatment to form conductive electrodes. Successful RIJ printing of MOD inks has been demonstrated; however, the fundamental understanding of droplet deposition involved in RIJ printing is lacking. Herein, the effect of substrate temperature and nozzle temperature during inkjet printing of copper MOD ink on the deposition morphology is investigated. It exhibits distinct behaviors in the deposition morphology at elevated temperatures when compared with the ones at room temperature. The different deposition morphology of the copper ink at various temperatures is attributed to the generation of a localized seeding layer which attracts the copper ions to deposit. In addition, the copper MOD ink printing is compared with a silver MOD ink. The different deposition morphology between the copper ink and silver ink is due to the solvent system. Understanding the deposition mechanism for reactive inks provides valuable information and guidance in the fabrication of printed functional devices using particle‐free reactive inks.
Ultra‐Soft Liquid‐Ferrofluid Interfaces
Authors: Dev Arvind Arun , Hermans Thomas M. , Doudin Bernard
Published: September 2024

Soft interfaces are ubiquitous in nature, governing quintessential hydrodynamics functions, like lubrication, stability, and cargo transport. It is shown here how a magnetic pressure at a magnetic–nonmagnetic fluid interface results in an ultra‐soft interface with nonlinear elasticity and tunable viscous shear properties. The balance between magnetic pressure, viscous stress, and Laplace pressure results in a deformed and stable liquid‐in‐liquid tube with apparent elasticity in the range of 2–10 kPa, possibly extended by a proper choice of liquid properties. Such highly deformable liquid–liquid interfaces of arbitrary shape with vanishing viscous shear open doors to unique microfluidic phenomena, biomaterial flows and complex biosystems mimicking.
Human Serum Albumin‐Coated 10B Enriched Carbon Dots as Targeted “Pilot Light” for Boron Neutron Capture Therapy
Authors: Zhong Tianyuan , Yang Yongjin , Pang Miao , Pan Yong , Jing Shiwei , Qi Yanxin , Huang Yubin
Published: September 2024

Boron neutron capture therapy (BNCT) is a physiologically focused radiation therapy that relies on nuclear capture and fission processes. BNCT is regarded as one of the most promising treatments due to its excellent accuracy, short duration of therapy, and low side effects. The creation of novel boron medicines with high selectivity, ease of delivery, and high boron‐effective load is a current research topic. Herein, boron‐containing carbon dots (BCDs) and their human serum albumin (HSA) complexes (BCDs‐HSA) are designed and synthesized as boron‐containing drugs for BNCT. BCDs (10B: 7.1 wt%) and BCDs‐HSA exhibited excitation‐independent orange fluorescent emission which supported the use of fluorescence imaging for tracking 10B in vivo. The introduction of HSA enabled BCDs‐HSA to exhibit good biocompatibility and increased tumor accumulation. The active and passive targeting abilities of BCDs‐HSA are explored in detail. Subcutaneous RM‐1 tumors and B16‐F10 tumors both significantly decrease with BNCT, which consists of injecting BCDs‐HSA and then irradiating the area with neutrons. In short, this study provides a novel strategy for the delivery of boron and may broaden the perspectives for the design of boron‐containing carbon dots nanomedicine for BNCT.
Understanding Boron Chemistry as the Surface Modification and Electrolyte Additive for Co‐Free Lithium‐Rich Layered Oxide
Authors: Park Na Ri , Zhang Minghao , Han Bing , Li Weikang , Qian Kun , Nguyen HongNam , Kumakura Shinichi , Meng Ying Shirley
Published: September 2024

Lithium‐rich layered oxide (LRLO) stands out as a highly promising cathode material for the next generation of Li‐ion batteries, owing to its exceptional lithium storage capacity. The absence of cobalt in LRLO's composition provides an additional advantage, enabling cost‐effective production and thereby improving the feasibility of large‐scale manufacturing. Despite these promising attributes, LRLO has encountered challenges related to poor cycling performance and severe voltage decay, impeding its practical application. In addressing these challenges, a surface modification technique involving lithium borate (LBO) is employed through a dry coating method. The LBO‐coated LRLO exhibits a uniform surface layer with a thickness of 15 nm. Furthermore, the performance of LBO‐coated LRLO in a full cell is synergistically enhanced when combined with lithium bis(oxalato)borate (LiBOB) as an electrolyte additive. A discharge capacity retention of 82% is achieved after 400 cycles at room temperature. These substantial improvements are attributed to the continual reaction between boron species on the LRLO cathode surface and PF6− anions in the electrolyte. This reaction generates BF4− and suppresses HF acid formation during the high voltage charging process, demonstrating LRLO's potential for practical implementation.
Electric Double Layer Theory of Interfacial Ionic Liquids for Capturing Ion Hierarchical Aggregation and Anisotropic Dynamics
Authors: Wang Qiang , Qu Zhiguo , Tian Di
Published: September 2024

Compared to aqueous ions, ionic liquids (ILs) consist entirely of cations and anions, and they function in energy conversion and storage owing to unique properties. Classical electric double layer (EDL) theory born a century ago gives essential insights into aqueous interfaces, whereas it fails in ILs due to overlooking ionic geometries and interactions, leaving a theoretical gap in describing IL interfaces. This study captures IL fingerprints by combining nuclear magnetic resonance experiments, quantum chemistry investigations, and first‐principles molecular simulations. Based on these findings, an EDL theory is proposed to reflect hierarchical aggregation structure and anisotropic dynamics for interfacial ILs. It involves four elements including ion geometries, ion–ion interactions, ion–wall interactions, and temperature and interfacial electric field effects. Specifically, polyatomic ions with nonuniform shapes are cornerstones for successive elements. Cation–anion non‐oxygen hydrogen bonds and cation–cation π+–π+ stacking generate bound clusters. Ion–wall adsorption causes hierarchical aggregation patterns, and cation–wall parallel stacking creates anisotropic dynamics at interfaces. Moreover, the thermal‐weakened ionic interactions and electric field‐enhanced interfacial electron transfer alter the aggregation states and dynamic properties of interfacial ILs. This theory is adaptable to various IL–wall combinations, advancing electrolyte design for next‐generation electrochemical energy devices.
Programmable Persistent Room Temperature Phosphorescence Switches through Wavelength‐Selective Photoactivation
Authors: Wang Yuchang , Shao Aiwen , Li Jiangang , Wei Juan , Wei Kuanjian , Liu Shujuan , Ma Yun , Zhao Qiang
Published: September 2024

Controlling multicolor persistent room‐temperature phosphorescence (RTP) through photoirradiation holds fundamental significance but remains a significant challenge. In this study, we engineered a wavelength‐selective photoresponsive system utilizing the Förster resonance energy transfer strategy. This system integrates a photoactivated long‐lived luminescent material as the energy donor with a fluorescent photoswitch as the energy acceptor, facilitating programmable persistent luminescence switches. Distinct afterglow color states, such as initial nonemissive, green, yellow, and orange, were achieved through irradiation at 400 nm, 365 nm, and 254 nm, respectively. Based on this capability, we established an interacting network for multistate afterglow color switching among these four emissive states. In addition, we demonstrate the potential of this wavelength‐selective photoresponsive system in the photo‐controlled rewritable printing of multicolor afterglow images on a single thin film. This work represents a substantial step towards the fabrication of sophisticated wavelength‐selective photoresponsive systems, potentially revolutionizing applications in optical data storage, security labeling, and smart displays by enabling precise control over photoresponsive behaviors under various photoirradiation wavelengths.
Microfluidization outperforms homogenization: Optimizing stability and bioaccessibility in krill oil emulsions
Authors: Huang Jia‐rong , Zhang Jian‐run , Zhang Jing , Shao Zhen‐wen , Zhou Da‐yong , Song Liang
Published: September 2024

This research presents a rigorous comparative analysis of high‐pressure homogenization (HPH) and microfluidization (MF) for the production of krill oil (KO) emulsions, scrutinizing their impact on oxidative stability, bioaccessibility, and the behavior under in vitro simulated digestion. Our findings revealed that MF emulsions possessed a distinct advantage, with a droplet size and distribution that promoted exceptional oxidative stability, evidenced by a sustained reduction in oxidative markers and enhanced retention of bioactive components, including EPA and DHA, and the potent antioxidant astaxanthin. In contrast, HPH yielded larger and less uniform particles, correlating with diminished stability. The in vitro digestion studies underscored the superior bioaccessibility of MF emulsions, with a pronounced release of free fatty acids during the intestinal phase, indicative of an optimized digestion and absorption process due to the smaller droplet size of the emulsions. The study's insights advocate for the adoption of microfluidization in the food industry for the development of advanced delivery systems for n‐3 fatty acids, particularly in the context of KO‐based products. The technique shows promise in enhancing the quality, stability, and bioavailability of these products, which are rich in health‐promoting lipids. The microfluidization technique emerges as a promising avenue for the fortification of a diverse range of commercial food, beverage, and pharmaceutical products with lipids that contribute to health and wellness.
Green Electrolytes for Aqueous Ion Batteries: Towards High‐Energy and Low‐Temperature Applications
Authors: Park Eunbin , Jeong Jiwon , Sung Yung‐Eun , Yu Seung‐Ho
Published: September 2024

Aqueous battery systems are increasingly recognized for their potential as environmentally friendly next‐generation energy storage solutions. However, their commercialization faces challenges due to the need for electrolytes that can operate stably at high voltages and in low‐temperatures. Traditional approaches to address these issues often involve materials that compromise the green nature. This review highlights the importance of developing environmentally friendly materials to improve the performance of aqueous electrolytes under high voltage in different types of aqueous electrolytes such as water‐in‐salt, molecular crowding electrolytes, eutectic electrolytes and cosolvents. In addition, we review advances in different types of aqueous electrolytes focused on using sustainable materials to achieve stable electrolytes at low‐temperature by suppressing water crystallization and lowering the freezing point. By integrating these innovations, we envision a future where aqueous batteries offer both high performance and eco‐friendliness, contributing significantly to the development of sustainable energy systems.
Synergistic Action of Vanillic Acid‐Coated Titanium Oxide Nanoparticles: Targeting Biofilm Formation Receptors of Dental Pathogens and Modulating Apoptosis Genes for Enhanced Oral Anticancer Activity
Authors: Rafe Hatshan Mohammad , Perianaika Matharasi Antonyraj Anahas , Marunganathan Vanitha , Rafi Shaik Mohammed , Deepak Paramasivam , Thiyagarajulu Nathiya , Manivannan Chandrakumar , Jain Divya , Melo Coutinho Henrique Douglas , Guru Ajay , Arockiaraj Jesu
Published: September 2024

The prevalence of bacterial and fungal infections is caused by S. aureus, S. mutans, E. faecalis, and Candida albicans are often associated with dental illnesses. In the present study, a unique strategy was used to combat these diseases by fabricating titanium dioxide nanoparticles (TiO2 NPs) conjugated with the plant‐based molecule vanillic acid (VA). To confirm the structural characterization of the synthesized VA‐TiO2 NPs, an extensive analysis was carried out utilizing methods such as SEM, FTIR, and XRD. Assessments for scavenging reactive oxygen species were performed to evaluate its antioxidant capability. Furthermore, a zone of inhibition test targeting pathogenic oral bacteria was used to assess the antibacterial efficacy of VA‐TiO2 NPs. Molecular modeling investigations were performed to better understand the interactions among vanillic acid and dental pathogen receptors using the Autodock program. The findings indicated that VA‐TiO2 NPs exhibited strong free radical scavenging activity. Additionally, they showed excellent antibacterial action towards dental pathogens, with a minimum inhibition level of 60 μg/mL. Furthermore, at doses of 15 μg/mL, 30 μg/mL, 60 μg/mL, and 120 μg/mL, VA‐TiO2 NPs demonstrated concentration‐dependent apoptotic impacts on human oral carcinoma cells. Apoptotic gene over‐expression was identified by the molecular perspectives that revealed the anticancer mechanism of VA‐TiO2 NPs on KB cells. This study highlights the promising suitability of VA‐TiO2 NPs for dental applications due to their robust antioxidant, anticancer, and antimicrobial characteristics. These nanoparticles present an evident prospect for addressing oral pathogen challenges and improving overall oral health.
Molecular Networking‐Guided Discovery of a New Antitumor Pyranonaphthoquinone from Streptomyces tanashiensis DSM 731: Insights from Single‐Molecule Stretching Assays
Authors: Cai Teng , Ding Nanjin , He Yulong , Han Tao , Wang Yanyan , Liu Chengxin , He Qiqi , Liu Chen , Li Aiying , Zhang Peng , Cai Xiaofeng
Published: September 2024

Guided by molecular networking based on single‐molecule stretching assay, an unprecedented pyranonaphthoquinone, methyl kalafunginate (1) and five known compounds 2–6 were isolated from Streptomyces tanashiensis DSM 731. Compound 1 was characterized through a combination of spectroscopic techniques, including 1D and 2D NMR analysis, ECD calculation, and X‐ray crystallography. Interestingly, we discovered that compound 1 was spontaneously converted from kalafungin (4) in methanol solution. All isolated compounds, except for compound 3, were assessed for their cytotoxic potential against a panel of five human cancer cell lines: A549, HepG2, BxPC‐3, SW620, and C4‐2B. Compounds 1, 2, 4, and 5 exhibited remarkable cytotoxicity with IC50 values below 2.382 μM, suggesting their potential as promising anticancer agents. These findings highlight the significance of using a combined approach of single‐molecule stretching assays and molecular networking for efficiently discovering novel natural products with potential therapeutic applications.
Maxillary herpes zoster with nasociliary nerve involvement and Klebsiella superinfection: A rare occurrence
Authors: Adjei Prosper , Asasu Stanley Anenyemele , Ayeebo Michael Lennart , Donkor Eunice Ansomah , Amoakohene‐Yeboah Augustina
Published: September 2024

Key Clinical Message

Herpes zoster is an acute cutaneous viral disease resulting from reactivation of dormant varicella‐zoster virus. The maxillary nerve is the least frequently affected branch of the trigeminal nerve. Rarely, cutaneous lesions can be secondarily infected with Klebsiella species. This report discusses a case of maxillary zoster with nasociliary nerve involvement and Klebsiella superinfection.
Spirocyclopropanes and Substituted Furans by Controlling Reactivity of 1,3‐Enynoates: γ‐ and δ‐Addition of Phosphines to Conjugate Acceptors
Authors: Chen Szu‐Han , Chen Yi‐Liang , Chen Chun‐Yu , Wu Chi‐Shiun , Su Ming‐Der , Chuang Shih‐Ching
Published: September 2024

In the Morita‐Baylis‐Hillman (MBH) reaction, a nucleophile undergoes β‐addition to activated alkenes or alkynes, forming reactive intermediates for subsequent carbon‐carbon or carbon‐hetero bond formation. By using a π‐conjugated acceptor, however, an unprecedented reactivity of 1,3‐enynoates and indane‐1,3‐diones was uncovered in the presence of phosphines. When indan‐1,3‐diones were used, γ‐addition of phosphines to 1,3‐enynoates was observed for the first time; moderate to good yields were obtained for 14 substances containing the prominent spirocyclopropane scaffold with 100 % retention of (Z)‐alkene. When 2‐methyl‐indan‐1,3‐diones were used, di(tri)‐substituted furans were produced through the δ‐addition pathway, with 20 substances and a yield of up to 88 % being achieved. Control experiments and density functional theory calculations were conducted to obtain insights into the unconventional γ‐addition reaction pathway.
A Cycloparaphenylene Acetylene as Potential Precursor for an Armchair Carbon Nanotube
Authors: Sidler Eric , Röthlisberger Ramon , Mayor Marcel
Published: September 2024

The bottom‐up synthesis of carbon nanotubes (CNTs) is a long‐standing goal in synthetic chemistry. Producing CNTs with defined lengths and diameters would render these materials and thus their fascinating properties accessible in a controlled way. Inspired by a recently reported synthesis of armchair graphene sheets that relied on a benzannulation and Scholl oxidation of a poly(p‐phenylene ethynylene), the same strategy is applied on a cyclic substrate with a short, but well defined CNT as target structure. Herein we report the synthesis of a derivatized [12]cycloparaphenylene acetylene ([12]CPPA) that was accessible employing a Sonogashira macrocyclization. The obtained macrocycle is the largest [n]CPPA reported to date and displays bright turquoise fluorescence with a large quantum yield of 77 %. The [12]CPPA can be transformed by a 12‐fold benzannulation that converts each alkyne to a naphthalene and therefore allows formation of an armchair [12,12]CNT precursor. The final 72‐fold Scholl oxidation to the [12,12]CNT turned out to be challenging and its optimization requires an improved synthetic strategy to produce large quantities of the final precursor. The developed approach poses a potential break through strategy for the production of CNTs and certainly incentivizes synthetic chemists to apply the same methodology for various conjugated macrocycles.
Impacts of post‐operation loading and fixation implant on the healing process of fractured tibia
Authors: Doorandish Yazdi Shima , Hedayat Dorna , Asadi Amir , Abouei Mehrizi Ali
Published: September 2024

Healing of tibia demonstrates a complex mechanobiological process as it is stimulated by the major factor of strains applied by body weight. The effect of screw heads and bodies as well as their pressure distribution is often overlooked. Hence, effective mechanical conditions of the healing process of tibia can be categorized into the material of the plate and screws, post‐operation loadings, and screw type and pressure. In this paper, a mathematical biodegradation model was used to simulate the PGF/PLA plate‐screw device over 8 weeks. The effect of different post‐operation loading patterns was studied for both locking and non‐locking screws. The aim was to reach the best configuration for the most achievable healing using FEA by computing the healing pattern, trend, and efficiency with the mechano‐regulation theory based on deviatoric strain. The biodegradation process of the plate and screws resulted in 82% molecular weight loss and 1.05 GPa decrease in Young's modulus during 8 weeks. The healing efficiency of the cases ranged from 4.72% to 14.75% in the first week and 18.64% to 63.05% in the eighth week. Finally, an optimal case was achieved by considering the prevention of muscle erosion, bone density reduction, and nonunion, according to the obtained results.
Potential genetic gains from targeted recombination versus recurrent selection for maize yield and moisture
Authors: Cameron John N. , Bernardo Rex
Published: September 2024

Recurrent selection is a proven method and targeted recombination is a potential method for achieving genetic gain. Our objectives were to determine the (1) equivalency in predicted gains between cycles of recurrent selection and targeted recombination in maize (Zea mays L.), (2) correspondence between targeted‐recombination positions when gains from nontargeted chromosomes are considered versus ignored, and (3) trade‐offs in predicted gains for yield and moisture in targeted recombination. From genomewide marker effects for 2911 single nucleotide polymorphism loci in 270 biparental populations, we obtained predicted gains from fixed numbers of targeted recombinations and compared these gains to the genotypic‐value distributions of doubled haploids obtained from different cycles of simulated recurrent selection. On average, it took three cycles of single‐trait recurrent selection to obtain at least a few doubled haploid lines with the same performance achieved with nine or 10 targeted recombinations in Cycle 0. Results indicated that when targeting recombinations across the genome, gains from segregation on nontargeted chromosomes do not need to be considered. Predicted increases in yield were associated with increases in moisture. Given the logistics of pyramiding targeted recombinations and the lack of mature technologies for routine targeted recombination, recurrent selection is currently the preferred approach for accumulating favorable recombinations.
Exploring traditional and novel spike traits associated with seed retention in perennial ryegrass by integrating 2D and 3D image analysis
Authors: Tubbs Travis B. , Chastain Thomas G.
Published: September 2024

Seed shattering is a major economic problem in seed production of perennial ryegrass (Lolium perenne L.). The objective was to identify potential relationships between phenotypic traits and seed retention in a 2‐year field trial with 21 diverse global accessions of perennial ryegrass. Accessions were grouped according to level of seed retention. Phenotypic traits examined were growth habit, spike length, curvature of the spike, spikelets per spike, spikelet length, internode length between spikelets, angle of spikelet insertion into the rachis, seeds per spike, and seed weight. Traits were captured and measured by use of novel two‐dimensional (2D) and three‐dimensional (3D) imaging tools. Among accessions, median seed retention values for the high and low seed retention groups were 61% and 36%, respectively. Four traits were found to significantly impact seed shattering: spike length (p ≤ 0.01), seed weight (p ≤ 0.001), seeds per spike (p ≤ 0.05), and internode length between spikelets (p ≤ 0.01). Seed retention was highest in accessions with short spikes. Most of the accessions that had high seed retention also had lower mean seed weight than the commercial plant materials. Accession (PI 231620) had both high levels of seed retention and a mean seed weight that is acceptable in the marketplace. These qualities may be used to improve seed retention in the breeding of perennial ryegrass cultivars. The 2D and 3D imaging methods have applicability in measurement of other plant morphological traits and across a broad range of plant species.
Prospective assessment of probe‐based confocal laser endomicroscopy under direct cholangioscopic visualization for biliary strictures that could not be definitively diagnosed using endoscopic retrograde cholangiopancreatography (with video)
Authors: Tanisaka Yuki , Ryozawa Shomei , Mizuide Masafumi , Fujita Akashi , Jinushi Ryuhei , Watanabe Ryuichi , Sato Ryo , Tashima Tomoaki , Mashimo Yumi
Published: September 2024

The definitive diagnosis of patients with indeterminate biliary strictures remains challenging. Probe‐based confocal laser endomicroscopy (pCLE) provides real‐time histological assessment of bile duct tissues. Since no previous studies have evaluated the efficacy of pCLE under direct cholangioscopic visualization for biliary strictures that cannot be definitively diagnosed through endoscopic retrograde cholangiopancreatography using fluoroscopy, we prospectively assessed the feasibility and safety of this procedure in three cases. pCLE findings were obtained in three cases, providing accurate diagnoses. Additionally, no adverse event was reported. pCLE under direct cholangioscopic visualization for indeterminate biliary strictures might be feasible and safe, even though these strictures were not previously diagnosed using endoscopic retrograde cholangiopancreatography. Further studies with more cases are warranted to clarify the effectiveness of pCLE under direct cholangioscopic visualization.
A rigid‐flexible coupled rocking structure with nonlinear stress distribution along its base: Analytical modeling, validation and parametric investigation
Authors: Bao Yu , Liu Ying‐Qi
Published: September 2024

Structures allowing their bases to uplift and rock during an earthquake event usually experience less damage; thus, they are more resilient to seismic hazards. Accurate simulation is critical to design and seismic performance evaluation of these flexible rocking structures. Motivated from this, this article presents a new rigid‐flexible coupled rocking model for numerical evaluation of flexible rocking structures under both cyclic and dynamic loadings. The key idea in the model formulation is that the total motion of flexible rocking structure can be decomposed into a rigid‐body motion and an associated flexible deformation. The flexible deformation of the rocking body is described using displacement field of classical Timoshenko beam. Using this approach and appropriate degrees‐of‐freedom (DOFs), the governing equations‐of‐motion for flexible rocking structures are formulated using the variational principle. Multiple springs with appropriate constitutive model are distributed along rocking base to represent the inelastic behavior of rocking body. Potential post‐tensioned tendons are also considered in this model. In addition, nonlinear stress distribution along the rocking base, which cannot be considered in existing flexible rocking model, is also incorporated in the developed model. The proposed model is subsequently validated against published experimental data through quasi‐static and shake table tests, showing good accuracy when the rocking structure is relatively stockier. Finally, a parametric investigation on the effect of flexibility, nonlinear stress distribution and yield stress of rocking body on the rocking response is performed. This preliminary investigation shows that influence of flexibility and yield stress is significant while impact of nonlinear stress distribution is minor.
Diagnostic and Therapeutic Implications of a FUS::TFCP2 Fusion and ALK Activation in a Metastatic Rhabdomyosarcoma
Authors: Csizmok Veronika , Grisdale Cameron J. , Williamson Laura M. , Lim Howard J. , Lee Lawrence , Renouf Daniel J. , Jones Steven J. M. , Marra Marco A. , Laskin Janessa , Smrke Alannah
Published: September 2024

The identification of gene fusions in rare sarcoma subtypes can have diagnostic, prognostic, and therapeutic impacts for advanced cancer patients. Here, we present a case of a 31‐year‐old male with a lytic lesion of the left mandible initially diagnosed as an osteosarcoma but found to have a TFCP2 fusion and ALK alteration, redefining the diagnosis and providing rationale for a novel treatment strategy. Histologically, the tumor displayed hypercellular, spindled to epithelioid neoplasm and nuclear pleomorphism, while immunohistochemistry showed diffuse SATB2 and focal desmin staining. Whole genome and transcriptome analysis revealed a FUS::TFCP2 fusion, the defining alteration of a rare molecularly characterized subtype of soft tissue sarcoma termed intraosseous rhabdomyosarcoma. An internal ALK deletion and extremely high ALK RNA expression were also identified, suggesting potential benefit of an ALK inhibitor. This patient displayed a rapid and dramatic clinical and radiographic response to an ALK inhibitor, alectinib. Unfortunately, the response was short‐lived, likely due to the advanced stage and aggressiveness of the disease. This report describes genome and transcriptome characterization of an intraosseous rhabdomyosarcoma, few of which exist in the literature, as well as providing evidence that inhibition of ALK may be a rational treatment strategy for patients with this exceedingly rare soft tissue sarcoma subtype characterized by TFCP2 fusions and ALK activation.
17p13 (TP53) Deletions Are Associated With an Aggressive Phenotype but Unrelated to Patient Prognosis in Urothelial Bladder Carcinomas
Authors: Kluth Martina , Hitzschke Melanie , Furlano Kira , Plage Henning , Hofbauer Sebastian , Weinberger Sarah , Ralla Bernhard , Fendler Annika , de Martino Michela , Roßner Florian , Schallenberg Simon , Elezkurtaj Sefer , Lennartz Maximilian , Marx Andreas H. , Samtleben Henrik , Fisch Margit , Rink Michael , Slojewski Marcin , Kaczmarek Krystian , Ecke Thorsten , Koch Stefan , Adamini Nico , Weischenfeldt Joachim , Klatte Tobias , Minner Sarah , Simon Ronald , Sauter Guido , Schlomm Thorsten , Horst David , Zecha Henrik
Published: September 2024

17p13 deletions including TP53 and other genes represent a common cause for reduced/lost p53 function in tumor cells. In this study, we analyzed the impact of 17p13 (TP53) deletions and p53 expression on tumor aggressiveness and patient prognosis in urothelial carcinoma. The 17p13 copy number status was analyzed by fluorescence in situ hybridization (FISH) on more than 2700 urothelial bladder carcinomas in a tissue microarray format. 17p13 deletion data were compared to p53 expression data measured by immunohistochemistry (IHC) in a previous study. Different types of p53 alterations were compared with tumor phenotype and clinical outcome data. Deletions of 17p13 occurred in 23% of 2185 analyzable carcinomas. The fraction of tumors with 17p13 deletions increased from pTa G2 low (9%) to pTa G3 (24%, p < 0.0001). In muscle‐invasive carcinomas, 17p13 deletions were associated with advanced pT stage (p = 0.0246), but unrelated to patient prognosis (p > 0.5). 17p13 deletions were significantly related to p53 immunostaining (p = 0.0375). 17p13 deletions were most common in tumors with complete lack of p53 staining (31%), which supports the concept that many of these tumors have a complete loss of p53 function (p53 null phenotype). 17p13 deletions were also increased in tumors with high p53 staining (25%). In conclusion, 17p13 deletions were most commonly seen in p53 negative cancers, supporting their role as a cause for the p53 null phenotype in urothelial cancer. The association of 17p13 deletions with high grade and advanced pT stage may reflect increasing genomic instability going along with stage and grade progression.
Effects of virtual reality on stroke rehabilitation: An umbrella review of systematic reviews
Authors: Hao Jie , Crum Gretchen , Siu Ka‐Chun
Published: September 2024

Background and Aims

Virtual reality is an emerging technology in rehabilitation. This umbrella review aimed to identify, critically appraise, and summarize current systematic reviews on the effects of virtual reality on stroke rehabilitation.

Methods

Five biomedical databases, PubMed, Embase, CINAHL, PsycINFO, and Scopus were searched from inception to December 30th, 2023, for systematic reviews with or without meta‐analyses published in English. Two reviewers independently conducted abstract screening, full‐text selection, and quality assessments. The methodological quality of included studies was evaluated by the Assessing the Methodological Quality of Systematic Reviews 2. Results were qualitatively synthesized according to domains of function to ascertain the effects of virtual reality intervention on functional improvement within stroke rehabilitation.

Results

A total of 78 articles were included; 23 were systematic reviews, and 55 were systematic reviews with meta‐analyses. Among them, 30 studies were evaluated as critically low quality, 32 as low, 15 as moderate, and one as good. Outcomes regarding upper extremity motor function, upper extremity activity, participation, functional independence, balance, functional mobility, walking speed, and cognitive function were summarized. While positive effects in favor of virtual reality were revealed by a majority of systematic reviews on these outcomes, evidence supporting the significantly different effects of virtual reality compared to conventional rehabilitation on participation and cognitive function was lacking.

Conclusion

The umbrella review demonstrated promising clinical outcomes regarding the use of virtual reality as an advanced therapeutic approach in stroke rehabilitation to optimize patient care. Future systematic reviews and meta‐analyses in this field should adhere to established guidelines to enhance the quality of evidence.
Unlocking the medicinal arsenal of Cissus assamica: GC‐MS/MS, FTIR, and molecular docking insights
Authors: Taher Mohammad Abdullah , Kundu Ripa , Laboni Aysha Akter , Shompa Suriya Akter , Moniruzzaman Md. , Hasan Mohammad Mahmudul , Hasnat Hasin , Hasan Md. Mehedi , Khan Mala
Published: September 2024

Background and aims

This study investigated the biochemical components present in the leaves of Cissus assamica. The primary aim was to analyze these components using advanced techniques and assess their potential therapeutic applications.

Methodology

Fourier Transform Infrared (FT‐IR) spectroscopy, Gas Chromatography‐Mass Spectrometry (GC‐MS), and Mass Spectral analysis were employed to identify and characterize the compounds in Cissus assamica leaves. The mass spectra of each compound were compared with data from the Wiley and NIST libraries to determine their names, molecular masses, and chemical structures. FT‐IR analysis identified characteristic functional groups by their specific frequencies.

Results and discussion

FT‐IR spectroscopic analysis revealed significant molecular vibrations at frequencies of 3265.63, 2853.81, 1638.60, 1469.21, and 1384.95 cm⁻¹, indicating the presence of specific functional groups. The GC‐MS analysis identified distinct compounds, such as “aR‐Turmerone,” “Curlone,” “7,8‐Epoxylanostan‐11‐ol, 3‐acetoxy‐,” “13‐Docosenamide, (Z)‐,” “Phenol, 3,5‐bis(1,1‐dimethylethyl)‐,” “9,19‐Cyclolanostan‐3‐ol, 24,24‐epoxymethano‐, acetate,” and “Quinoline‐5,8‐dione‐6‐ol, 7‐[[(4‐cyclohexylbutyl)amino]methyl]‐.” These compounds exhibited potential therapeutic applications. Their cytotoxic, antimicrobial, antidiarrheal, anti‐hyperglycemic, and pain‐relieving properties were evaluated by comparing them with reference ligands targeting specific receptors, including dihydrofolate reductase (DHFR), epidermal growth factor receptor (EGFR), kappa opioid receptor (KOR), glucose transporter 3 (GLUT 3), and cyclooxygenase 2 (COX‐2).

Conclusion

The results of this study suggest that Cissus assamica leaves contain bioactive compounds with potential therapeutic benefits for treating infections, diarrhea, hyperglycemia, and pain. However, further research is needed to conduct comprehensive phytochemical screening and establish the precise mechanisms of action for the crude extract or the plant‐derived compounds.
Development of a machine learning‐based target‐specific scoring function for structure‐based binding affinity prediction for human dihydroorotate dehydrogenase inhibitors
Authors: Meng Jinhui , Zhang Li , He Zhe , Hu Mengfeng , Liu Jinhan , Bao Wenzhuo , Tian Qifeng , Feng Huawei , Liu Hongsheng
Published: September 2024

Human dihydroorotate dehydrogenase (hDHODH) is a flavin mononucleotide‐dependent enzyme that can limit de novo pyrimidine synthesis, making it a therapeutic target for diseases such as autoimmune disorders and cancer. In this study, using the docking structures of complexes generated by AutoDock Vina, we integrate interaction features and ligand features, and employ support vector regression to develop a target‐specific scoring function for hDHODH (TSSF‐hDHODH). The Pearson correlation coefficient values of TSSF‐hDHODH in the cross‐validation and external validation are 0.86 and 0.74, respectively, both of which are far superior to those of classic scoring function AutoDock Vina and random forest (RF) based generic scoring function RF‐Score. TSSF‐hDHODH is further used for the virtual screening of potential inhibitors in the FDA‐Approved & Pharmacopeia Drug Library. In conjunction with the results from molecular dynamics simulations, crizotinib is identified as a candidate for subsequent structural optimization. This study can be useful for the discovery of hDHODH inhibitors and the development of scoring functions for additional targets.
Scalable production of siRNA‐encapsulated extracellular vesicles for the inhibition of KRAS‐mutant cancer using acoustic shock waves
Authors: Kim Hyo Kyeong , Choi Yujeong , Kim Kyoung Hwa , Byun Yeongju , Kim Tae Hee , Kim Jae Hwan , An Shung Hyun , Bae DaeHo , Choi Myeong Kwan , Lee Minyoung , Kang Gwansuk , Chung Jihwa , Kim Seok‐Hyun , Kwon Kihwan
Published: September 2024

Extracellular vesicles (EVs) have emerged as a potential delivery vehicle for nucleic‐acid‐based therapeutics, but challenges related to their large‐scale production and cargo‐loading efficiency have limited their therapeutic potential. To address these issues, we developed a novel “shock wave extracellular vesicles engineering technology” (SWEET) as a non‐genetic, scalable manufacturing strategy that uses shock waves (SWs) to encapsulate siRNAs in EVs. Here, we describe the use of the SWEET platform to load large quantities of KRASG12C‐targeting siRNA into small bovine‐milk‐derived EVs (sBMEVs), with high efficiency. The siRNA‐loaded sBMEVs effectively silenced oncogenic KRASG12C expression in cancer cells; they inhibited tumour growth when administered intravenously in a non‐small cell lung cancer xenograft mouse model. Our study demonstrates the potential for the SWEET platform to serve as a novel method that allows large‐scale production of cargo‐loaded EVs for use in a wide range of therapeutic applications.
Lateral meniscus posterior root repairs show superior healing, reduced meniscal extrusion and improved clinical outcomes compared to medial meniscus posterior root repairs: A systematic review
Authors: Dzidzishvili Lika , Pedemonte‐Parramón Gloria , Garcia‐Oltra Ester , López Vicente , Hernández‐Hermoso José A.
Published: September 2024

Purpose

To systematically review and summarize the available literature on (1) postoperative healing rates, meniscal extrusion (ME) and clinical outcomes following lateral (LMPRR) versus medial (MMPRR) root repair and (2) potential correlations between residual ME and healing outcomes.

Methods

A comprehensive literature search was conducted using the Scopus, PubMed and Embase databases. Clinical studies evaluating healing status on second‐look arthroscopy and magnetic resonance imaging (MRI) after LMPRR and MMPRR were included. Study quality was assessed using the Methodological Index for Non‐Randomized Studies criteria and the modified Coleman Methodology Score.

Results

Twenty‐three studies comprising 871 patients with LMPRR (n = 406) and MMPRR (n = 465) were included. Overall, 223 (54.9% of total) and 149 (32.04% of total) patients underwent second‐look arthroscopy in the LMPRR and MMPRR groups, respectively. Complete root healing was observed in 190 (85.2%) patients in the LMPRR group versus 78 (52.3%) in the MMPRR group (p < 0.001). There were six (2.7%) failed repairs in the LMPRR group compared to 21 (14.09%) in the MMPRR group (p < 0.001). On postoperative MRI, 109 (75.7%) root repairs were healed in the LMPRR group compared to 192 (53.3%) in the MMPRR group (p < 0.001). Failure rates were lower after all‐inside and transtibial pullout repairs in the LMPRR group but higher in the MMPRR group, with no significant mean difference between preoperative and postoperative ME in the MMPRR group (p = 0.95). Significantly better clinical outcomes were observed in the LMPRR group compared to the MMPRR group. A greater degree of postoperative ME was associated with lower healing rates (R = −0.78, p < 0.0005). Postoperative ME did not influence clinical outcomes (R = 0.28, p = 0.29).

Conclusions

Lateral meniscus posterior root repairs showed higher healing rates compared to MMPRR on both second‐look arthroscopy and postoperative MRI. Meniscal extrusion decreased after LMPRR but not after MMPRR. Greater residual ME correlated inversely with healing rates, as more extrusion was associated with lower healing. Postoperative clinical improvement did not affect ME or healing status.

Study Design

Systematic review of level III and IV studies.

Level of Evidence

Level IV.
Effect of tibia‐first, restricted functional alignment technique on gap width changes, and component positioning in robotic arm‐assisted total knee arthroplasty
Authors: Yang Hong Y. , Cheon Jae H. , Kang Sung J. , Seon Jong K.
Published: September 2024

Purpose

This study aims to quantitatively assess the predictability of post‐resection gap dimensions and the attainment of balanced gaps using robotic arm‐assisted total knee arthroplasty (TKA).

Methods

This retrospective cohort study included 100 consecutive patients who underwent robotic arm‐assisted TKA for knee osteoarthritis using a restricted functional alignment (FA) technique. Tibial cuts were performed based on preoperative tibial anatomy within predefined boundaries, followed by femoral component adjustments according to tensioned soft tissues to optimise gap balance. The primary outcome was the proportion of balanced gaps, defined as differential laxities of ≤2 mm, across extension, flexion, lateral, and medial gap measurements. Ligament balancing in lateral and medial compartments was assessed using a robotic system at 10° and 90° flexion to evaluate if restricted FA facilitated a balanced knee. Secondary outcomes included implant alignment, resection depth, and patient‐reported outcome measures (PROMs).

Results

Significant increases in both lateral and medial gaps at 10° and 90° flexion were observed following tibial and femoral bone resections (p < 0.001). At extension, average gap changes were 0.9 mm (lateral) and 1.6 mm (medial) after tibial cuts, and 0.5 mm (lateral) and 1.2 mm (medial) after femoral cuts. At 90° flexion, changes were 0.3 mm (lateral) and 1.7 mm (medial) following tibial cuts, and 1.0 mm (lateral) and 1.4 mm (medial) after femoral cuts. Despite these variations, the tibia‐first, gap‐balancing technique achieved overall balance in 98% of gap measurements. The tibial component was placed at an average of 2.1° varus, while the femoral component was positioned at 0.3° varus and 1.3° external rotation relative to the surgical transepicondylar axis. Significant improvements in PROMs were noted between preoperative and one‐year postoperative evaluations (all p < 0.05).

Conclusions

The tibia‐first, restricted FA technique achieved a well‐balanced knee in 98% of cases, despite inconsistent gap increments observed between initial assessments and post‐resection.

Level of Evidence

Therapeutic Level IV.
Dedicator of cytokinesis 8 (DOCK8) mutation impairs the differentiation of helper T cells by regulating the glycolytic pathway of CD4+ T cells
Authors: Jiang Panpan , Zhao Siyu , Li Xiaoyu , Hu Shiyan , Chen Shuhan , Liang Yinming , Zhang Lichen , Lu Liaoxun , Fang Guofeng , Yang Lu , Huang Yanmei , Miller Heather , Guan Fei , Lei Jiahui , Liu Chaohong
Published: September 2024

Dedicator of cytokinesis 8 (DOCK8) deficiency is a primary immunodeficiency disease caused by mutations in exon 45 of the DOCK8 gene. The clinical signs primarily consist of increased serum IgE levels, eczema, repeated skin infections, allergies, and upper respiratory tract infections. Using CRISPR/Cas9 technology, we generated a DOCK8 exon 45 mutation in mice, mirroring the mutation found in patients. The results indicated that DOCK8 mutation impairs peripheral T cell homeostasis, disrupts regulatory T cells (Tregs) development, increases ICOS expression in Tregs within peripheral lymph nodes (pLn), and promotes Th17 cell differentiation within the spleen and pLn. Upon virus infection, DOCK8 mutation CD4+ T cells have a Th2 effector fate. RNA‐bulk sequencing data revealed alternations in the mTOR pathway of DOCK8 mutant CD4+ T cells. We observed that DOCK8 mutation upregulates the glycolysis levels in CD4+ T cells, which is related to the Akt/mTOR/S6/HIF‐1α pathway. In summary, our research elucidates that DOCK8 regulates the differentiation of helper T cells by modulating the glycolytic pathway in CD4+ T cells, thereby advancing the comprehension and offering potential treatment of diseases in DOCK8‐deficient patients.