bluuebunny/crossref_metadata_2025 huggingface dataset:
Improvement of treatment plan quality with modified fixed field volumetric modulated arc therapy in cervical cancer
Authors: Jindakan Sirawat , Tharavichitkul Ekkasit , Watcharawipha Anirut , Nobnop Wannapha
Published: July 2024

Purpose

This study aims to introduce modified fixed field volumetric modulated arc therapy (MF‐VMAT) which manually opened the field size by fixing the jaws and comparing it to the typical planning technique, auto field volumetric modulated arc therapy (AF‐VMAT) in cervical cancer treatment planning.

Methods and materials

Previously treated twenty‐eight cervical cancer plans were retrospectively randomly selected and replanned in this study using two different planning techniques: AF‐VMAT and MF‐VMAT, resulting in a total of fifty‐six treatment plans. In this study, we compared both planning techniques in three parts: (1) Organ at Risk (OARs) and whole‐body dose, (2) Treatment plan efficiency, and (3) Treatment plan accuracy.

Results

For OARs dose, bowel bag (p‐value = 0.001), rectum (p‐value = 0.002), and left femoral head (p‐value = 0.001) and whole‐body (p‐value = 0.000) received a statistically significant dose reduction when using the MF‐VMAT plan. Regarding plan efficiency, MF‐VMAT exhibited a statistically significant increase in both number of monitor units (MUs) and control points (p‐values = 0.000), while beam‐on time, maximum leaf travel, average maximum leaf travel, and maximum leaf travel per gantry rotation were statistically significant decreased (p‐values = 0.000). In terms of plan accuracy, the average gamma passing rate was higher in the MF‐VMAT plan for both absolute dose (AD) (p‐value = 0.001, 0.004) and relative dose (RD) (p‐value = 0.000, 0.000) for 3%/3 and 3%/2 mm gamma criteria, respectively.

Conclusion

The MF‐VMAT planning technique significantly reduces OAR doses and decreases the spread of low doses to normal tissues in cervical cancer patients. Additionally, this planning approach demonstrates efficient plans with lower beam‐on time and reduced maximum leaf travel. Furthermore, it indicates higher plan accuracy through an increase in the average gamma passing rate compared to the AF‐VMAT plan. Consequently, MF‐VMAT offers an effective treatment planning technique for cervical cancer patients.
House Appropriations adds $500 million to SUPTRS block grant
Authors: Knopf Alison
Published: July 2024

Last week, the House Appropriations Committee voted on the Labor, Health and Human Services, Education, and Related Agencies Appropriations Act, 2025 (https://docs.house.gov/meetings/AP/AP00/20240710/117503/BILLS‐118‐FC‐AP‐FY2025‐AP00‐FY25LHHSFullCommitteeMark.pdf) and the result was to increase funding for the block grant used to prevent and treat substance use disorders (SUDs). The increase comes at the expense of the federal Centers for Disease Control and Prevention (CDC), an agency that has squandered much of the funding it got to fight the prescription opioid problem beginning more than a decade ago.
Exosomal Bupivacaine: Integrating Nerve Barrier Penetration Capability and Sustained Drug Release for Enhanced Potency in Peripheral Nerve Block and Reduced Toxicity
Authors: Cai Yuhao , Li Qi , Wesselmann Ursula , Zhao Chao
Published: July 2024

Peripherally injected local anesthetics exhibit limited ability to penetrate peripheral nerve barriers, which limits their effectiveness in peripheral nerve block and increases the risk of adverse effects. In this work, it is demonstrated that exosomes derived from Human Embryo Kidney 293 cells can effectively traverse the perineurium, which is the rate‐limiting barrier within PNBs that local anesthetics need to cross before acting on axons. Based on this finding, these exosomes are used as a carrier for bupivacaine (BUP), a local anesthetic commonly used in clinical settings. The in vitro assessments revealed that the prepared exosomal bupivacaine (BUP@EXO) achieves a BUP loading capacity of up to 82.33% and sustained release of BUP for over 30 days. In rats, a single peripheral injection of BUP@EXO, containing 0.75 mg of BUP, which is ineffective for BUP alone, induced a 2‐h sensory nerve blockade without significant motor impairments. Increasing the BUP dose in BUP@EXO to 2.5 mg, a highly toxic dose for BUP alone, extended the sensory nerve blockade to 12 h without causing systemic cardiotoxicity and local neurotoxicity and myotoxicity.
Strong, Smart, and Slippery Organo‐gels by Network Glassification
Authors: Zeng Liangpeng , Fu Yuanmao , Cui Hongyuan , Zhao Yonglong , Liu Yi , Lin Xinxing , Chao Tong , Guo Hui
Published: July 2024

Lubricant‐infused organo‐gels with low surface energy solvents represent an environment‐friendly lubricating material, while the poor mechanical performance incapacitates them to harsh and intricate service conditions. To address this challenge, a simple yet highly effective strategy to prepare strong, smart, and slippery organo‐gels by glassifying the polymer network is reported. As a proof of concept, appropriate amounts of rigid solvophobic poly(phenyl methacrylate) (PPMA) units are integrated into a solvophilic poly(cyclohexyl acrylate) (PCHA) network infiltrated with lubricant. Upon forming bicontinuous phase‐separated structures, the rigid solvent‐free PPMA segments stay in glassy states, serving as a load‐bearing phase to toughen the materials effectively. Meanwhile, the soft PCHA phase maintains lubricity and extensibility by holding a substantial amount of lubricant. Owing to the synergistic effect, the gels manifest glass‐like mechanical performance with high rigidity (46.6 MPa), strength (7.7 MPa), and toughness (23.7 kJ m−2). Moreover, the materials exhibit high thermo‐sensitivity with the elastic modulus reversibly decreasing from 46.6 MPa at 20 °C to 0.23 MPa at 50 °C, endowing the gels with shape‐memory properties. Furthermore, the organo‐gels display satisfactory anti‐adhesiveness to various foreign matters. Taken together, the work represents a facile and universal strategy to reinforce organo‐gels, thereby adapting them to various applications.
Mitigating Noise Current in 2D Perovskite Single Crystal Photodetectors for Imaging under Black‐Light Condition
Authors: Xi Yuying , Li Guohui , Ji Ting , Hao Yuying , Liu Shengzhong (Frank) , Liu Yucheng , Cui Yanxia
Published: July 2024

Weak‐light imaging plays a pivotal role in various fields such as astronomical photography, military nighttime surveillance, and biomedical imaging. The capability of photodetectors (PDs) in detecting weak‐light relies heavily on minimizing their noise current. In this study, the weak‐light detection performances of PDs constructed from PEA2MAn‐1PbnI3n+1 (n = 1, 2, 3) 2D perovskite single crystals are presented. Among these, the n = 1 PD showcases incredibly low noise current that induces an ultra‐low detection limit of 14 pW cm−2 under 532 nm light illumination, and a high detectivity of 3.25 × 1015 Jones. The n = 1 PD also meets imaging requirements even under black‐level illumination conditions of 75 pW cm−2. The investigation reveals that decreasing n value corresponds to an increase in the PEA+ ratios of cations, resulting in reduced defects and enhanced ion migration activation energy and exciton binding energy. These reduce noise current of devices from electron/hole, ion, and exciton dynamic behaviors. Notably, inhibiting ion migration can significantly improve the stability of the noise current baseline and facilitate the stable detection of weak signals. This study underscores the potential of 2D perovskites for advancing weak‐light imaging technologies, offering valuable insights for future development in this field.
Cation‐Infused Bilayer Ionomer Coating Enables High Partial Current Density Toward Multi Carbon Products in CO2 Electrolysis
Authors: Rashid Mohsina , Nabil Shariful Kibria , Adnan Muflih A. , Kannimuthu Karthick , Kibria Md Golam
Published: July 2024

Electrochemical CO2 reduction (eCO2R) stands as a pivotal technology for carbon recycling by converting CO2 into value‐added products. While significant strides have been made in generating multi‐carbon (C2+) products like ethylene (C2H4) and ethanol (C2H5OH) at industrial‐scale current densities with high Faradaic efficiency (FE), cathode flooding and (bi)carbonate salt accumulation remain a fundamental concern in an alkaline electrolyte. In this work, ion‐conducting polymers are used to tailor the micro‐environment mitigating cathode flooding and salt precipitation and thus, enhancing the local CO2 availability. The impact of cation and anion exchange ionomer layers, specifically Nafion and Sustainion XA‐9 are examined on overall eCO2R performance. The use of an ultra‐thin bilayer configuration significantly reduces cathode flooding and salt accumulation by ≈58% compared to commercial anion exchange membrane (AEM). Alongside, cation infusion improves the C─C bond formation inducing a favorable micro‐environment for selective C2+ formation. This cation‐infused bilayer ionomer (CIBLI) achieves a high partial current density of ≈284 mA cm−2 toward C2+ products maintaining a stable eCO2R performance for 24 hours (h). This scalable approach of directly deposited ultra‐thin CIBLI offers a minimal conversion energy of 117 GJ/ ton C2+ products with an energy efficiency (EE) of 29% at 350 mA cm−2 current density in one‐step CO2 conversion.
Rigid‐Flexible Coupled Dendritic Molecule Doping: General Approach to Activate Commercial Polymers into Harsh Condition‐Tolerant Multi‐Reusable Strong Supramolecular Adhesives
Authors: Feng Jie , Lin Ziwei , Zhang Yang , Fang Long , Zhu Qikai , Yu Dingshan
Published: July 2024

Developing functional adhesives combining strong adhesion, good recyclability and diverse harsh‐condition adaptability is a grand challenge. Here, we introduce a general dendritic molecule doping strategy to activate commercial polymers into a new family of supramolecular adhesives integrating high adhesion strength, ultralow temperature, water resistant and multi‐reusable properties. Our method involves rational design of a new rigid‐flexible coupled dendritic molecule—M4C8OH as a versatile dopant, while simple M4C8OH doping into commercial polymers can modulate internal and external non‐covalent interaction to enable H‐bonding enhanced interchain cross‐linking for tough cohesion along with enhanced interphase interaction. This endows 20 wt % M4C8OH‐doped polycaprolactone (PCL) adhesives (PCL‐M4C8OH) with improved adhesion strength on various substrates with the maximum increase up to 2.87 times that of PCL. In particular, the adhesion strengths of PCL‐M4C8OH on polymethyl methacrylate at 25 °C and −196 °C reach 4.67 and 3.58 MPa—1.9 and 2.3 times those of PCL and superior to diverse commercial adhesives and most reported adhesives. PCL‐M4C8OH also displays markedly‐improved multi‐usability and tolerance against ultralow temperature and diverse wet environments. Mechanism studies reveal the crucial role of M4C8OH molecular structures toward superior adhesion. Our method can be expanded to other polymer matrices, yielding diverse new supramolecular adhesives.
Dynamic Covalent Bonds Enabled Carbon Fiber Reinforced Polymers Recyclability and Material Circularity
Authors: Fan Xiaotong , Zheng Jie , Yeo Jayven Chee Chuan , Wang Sheng , Li Ke , Muiruri Joseph Kinyanjui , Hadjichristidis Nikos , Li Zibiao
Published: July 2024

Due to their remarkable features of lightweight, high strength, stiffness, high‐temperature resistance, and corrosion resistance, carbon fiber reinforced polymers (CFRPs) are extensively used in sports equipment, vehicles, aircraft, windmill blades, and other sectors. The urging need to develop a resource‐saving and environmentally responsible society requires the recycling of CFRPs. Traditional CFRPs, on the other hand, are difficult to recycle due to the permanent covalent crosslinking of polymer matrices. The combination of covalent adaptable networks (CANs) with carbon fibers (CFs) marks a new development path for closed‐loop recyclable CFRPs and polymer resins. In this review, we summarize the most recent developments of closed‐loop recyclable CFRPs from the unique paradigm of dynamic crosslinking polymers, CANs. These sophisticated materials with diverse functions, oriented towards CFs recycling and resin sustainability, are further categorized into several active domains of dynamic covalent bonds, including ester bonds, imine bonds, disulfide bonds, boronic ester bonds, and acetal linkages, etc. Finally, the possible strategies for the future design of recyclable CFPRs by combining dynamic covalent chemistry innovation with materials interface science are proposed.
Crystal structure, Hirshfeld surface analysis, molecular modeling, electrochemical properties, and potential medicinal activity of a novel binuclear Co(II) complex
Authors: Elsheemy Walid M. , Abdel Aziz Ayman A. , Ramadan Ramadan M. , Kozakiewicz‐Piekarz Anna , Sayed Mostafa A.
Published: July 2024

A quinoxaline‐based ligand, 6,7‐dimethyl‐2,3‐di(2‐pyridyl)quinoxaline (Me2dpq), and its unique binuclear Co(II)‐Me2dpq complex were prepared and analyzed using single crystal X‐ray diffraction and several spectroscopy techniques. Hirshfeld surface analyses were also used to clarify the Me2dpq ligand and the Co(II)‐Me2dpq crystal packing. The Co(II)‐Me2dpq complex crystallized in triclinic P‐1 space group and exhibited a distorted trigonal bipyramidal geometry around the cobalt(II) ion. Each Co(II) ion coordinated to a Me2dpq ligand through two N donor centers from pyridyl and quinoxaline rings along with a terminal Cl and two bridged Cl atoms. The binding properties of the ligand and its complex with CT‐DNA were studied by several techniques, namely UV–Vis spectroscopy, fluorescence quenching, viscosity measurements, thermal denaturation, and gel electrophoresis. The CT‐DNA binding interaction tests demonstrated that both the Co(II)‐Me2dpq complex and its parent ligand bind to DNA in an intercalative way. The antioxidant studies of the novel Co(II)‐Me2dpq complex illustrated significant activity against DPPH• and
radicals. The in vitro cytotoxic effect of Me2dpq ligand and its Co(II)‐complex on MCF‐7 and Hep‐G2 tumor cell lines was evaluated by using the MTT assay. The studies showed that the Co(II)‐Me2dpq complex had superior activity toward the tested cell lines. Molecular docking studies of synthesized compounds were employed to figure out the way they would associate with a biologically macromolecular target B‐DNA (PDB: 1BNA). Thus, this study is anticipated to provide novel opportunities for the successful utilization of the synthesized compounds in many medical domains.
New Cu (II) and Zn (II) metal chelates derived from azo‐Schiff bases: Synthesis, DNA/BSA binding, anticancer activity and molecular docking studies
Authors: Kahraman Sevgi , Gungor Ozge , Erkan Sultan , Karagoz Isik Didem , Kose Muhammet , Kurtoglu Mukerrem
Published: July 2024

In this study, new Cu (II) and Zn (II) chelates (3–6) of 3‐/or 4‐ethyl and azo chromophore groups (NN) containing Schiff base ligands (2‐{(E)‐[(4‐ethylphenyl)imino]methyl}‐4‐[(E)‐phenyldiazenyl]phenol, HL1 (1) and 2‐{(E)‐[(3‐ethylphenyl)imino]methyl}‐4‐[(E)‐phenyldiazenyl]phenol, HL2 (2) were prepared and characterized by the analytical and spectroscopic methods. Crystal structures of chelates 3, 4 and 6 were determined by single‐crystal X‐ray diffraction studies. The ligands behaved as bidentates, coordinating through the nitrogen atom of the azomethine group (CHN) and the oxygen atom of the α‐hydroxyl group (OH). The metal:ligand ratio in the prepared copper (II) and zinc (II) chelates was found to be 1:2 by analytical and spectral analysis. The bands in the infrared spectra of the metal chelates in the region of 522–504 cm−1 and 467–455 cm−1 are attributed to ν(MO) and ν(MN) vibrations, respectively. When the DNA binding activities of the compounds were examined, it was determined that compound 4 had the highest binding constant. Fluorescence and viscosity data showed that the compounds interact with DNA through minor grove binding mode. Furthermore, anticancer properties of the compounds were investigated. Ligand 2 was found to be highly effective against the HepG2 cell with an IC50 of 0.31 μM. In addition, structural analysis, frontier molecular orbitals, molecular electrostatic potential maps, Hirshfeld surface analysis of the synthesized compounds using computational chemistry methods and anticancer activity studies were carried out by molecular docking.
A critical review of therapeutic interventions in sickle cell disease: Progress and challenges
Authors: Ala Chandu , Joshi Renuka Parshuram , Gupta Pragya , Goswami Sangam Giri , Ramalingam Sivaprakash , Kondapalli Venkata Gowri Chandra Sekhar , Sankaranarayanan Murugesan
Published: July 2024

Sickle cell disease (SCD) is an autosomal recessive genetic disorder that occurs due to the point mutation in the β‐globin gene, which results in the formation of sickle hemoglobin (HbS) in the red blood cells (RBCs). When HbS is exposed to an oxygen‐depleted environment, it polymerizes, resulting in hemolysis, vaso‐occlusion pain, and impaired blood flow. Still, there is no affordable cure for this inherited disease. Approved medications held promise but were met with challenges due to limited patient tolerance and undesired side effects, thereby inhibiting their ability to enhance the quality of life across various individuals with SCD. Progress has been made in understanding the pathophysiology of SCD during the past few decades, leading to the discovery of novel targets and therapies. However, there is a compelling need for research to discover medications with improved efficacy and reduced side effects. Also, more clinical investigations on various drug combinations with different mechanisms of action are needed. This review comprehensively presents therapeutic approaches for SCD, including those currently available or under investigation. It covers fundamental aspects of the disease, such as epidemiology and pathophysiology, and provides detailed discussions on various disease‐modifying agents. Additionally, expert insights are offered on the future development of pharmacotherapy for SCD.
Structural characterization and bioactivity profiling of the fungal peptaibiotic tolypin reveal protective effects against influenza viruses
Authors: Eichberg Johanna , Oberpaul Markus , Hartwig Christoph , Geißler Andrea Helga , Culmsee Carsten , Vilcinskas Andreas , Böttcher‐Friebertshäuser Eva , Brückner Hans , Degenkolb Thomas , Hardes Kornelia
Published: July 2024

In a bioprospection for new antivirals, we tested nonribosomally biosynthesized polypeptide antibiotics in MDCK II cells for their actions on influenza A and B viruses (IAV/IBV). Only tolypin, a mixture of closely related 16‐residue peptaibiotics from the fungus Tolypocladium inflatum IE 1897, showed promising activity. It was selected for further investigation and structural characterization by ultrahigh performance liquid chromatography coupled to high‐resolution mass spectrometry (UHPLC‐HR‐MS/MS) and ultrahigh performance liquid chromatography coupled to in‐source collision‐induced dissociation tandem mass spectrometry (UHPLC‐isCID‐HR‐MS/MS), revealing 12 partially co‐eluting individual peptides that were fully sequenced. Since tolypin‐related efrapeptins are potent inhibitors of F1/Fo‐ATPase, we screened tolypin for its toxicity against MDCK II cells and larvae of the greater wax moth Galleria mellonella. We found that a nontoxic concentration of tolypin (1 µg/mL) reduced the titer of two IBV strains by 4–5 log values, and that of an H3N2 strain by 1–2 log values, but the H1N1pdm strain was not affected. The higher concentrations of tolypin were cytostatic to MDCK II cells, shifted their metabolism from oxidative phosphorylation to glycolysis, and induced paralysis in G. mellonella, supporting the inhibition of F1/Fo‐ATPase as the mode of action. Our results lay the foundations for future work to investigate the interplay between viral replication and cellular energy metabolism, as well as the development of drugs that target host factors.
A Class of Heptaphyrins with NIR Absorption Modulated by Metal Coordination and Nucleophilic Substitution
Authors: Huang Yanping , Zhu Bin , Li Qizhao , Baryshnikov Glib , Li Chengjie , Sha Feng , Wu Xin‐Yan , Ågren Hans , Xie Yongshu
Published: July 2024

The intensive interest in expanded porphyrins can be attributed to their appealing photoelectric and coordination behavior. In this work, an N‐confused heptaphyrin 1 was synthesized by an acid‐catalyzed [3+4] condensation reaction. The introduction of an N‐confused pyrrolic unit into the heptaphyrin macrocycle led to the formation of a figure‐eight‐like conformation with nonsymmetrical “NNNN” and “NNNC” coordination cavities employable for bimetallic coordination. As a result, chelation of 1 with Zn(II) and Cu(II) afforded mono‐Zn(II) complex 2 and bis‐Cu(II) complex 3, respectively, with the metal atoms exhibiting distorted square‐planar geometries. In complex 3, an oxygen atom is attached to the α‐C atom of N‐confused pyrrole D, and thus the N and C atoms of ring D participate in coordination within the two cavities. Interestingly, treatment of 1 with Cs2CO3 in MeOH resulted in regioselective substitution of all the seven para‐F atoms in the meso‐C6F5 groups as well as the α‐H of ring D by eight methoxy moieties. Complex 3 displays a red‐shifted absorption band edge of ca. 2200 nm, compared to that of ca. 1600 nm observed for 1. This work provides an example of incorporating an N‐confused pyrrole to construct expanded porphyrins with distinctive coordination behavior and tunable NIR absorption.
Substrate and nutrient manipulation during continuous cultivation of extremophilic algae, Galdieria spp. RTK 37.1, substantially impacts biomass productivity and composition
Authors: Buckeridge Emma , Caballero Carlos C. , Smith Daniel H. , Stott Matthew B. , Carere Carlo R.
Published: July 2024

The extremophilic nature and metabolic flexibility of Galdieria spp. highlights their potential for biotechnological application. However, limited research into continuous cultivation of Galdieria spp. has slowed progress towards the commercialization of these algae. The objective of this research was to investigate biomass productivity and growth yields during continuous photoautotrophic, mixotrophic and heterotrophic cultivation of Galdieria sp. RTK371; a strain recently isolated from within the Taupō Volcanic Zone in Aotearoa‐New Zealand. Results indicate Galdieria sp. RTK371 grows optimally at pH 2.5 under warm white LED illumination. Photosynthetic O2 production was dependent on lighting intensity with a maximal value of (133.5 ± 12.1 nmol O2 mgbiomass−1 h−1) achieved under 100 μmol m−2 s−1 illumination. O2 production rates slowed significantly to 42 ± 1 and <0.01 nmol O2 mgbiomass−1 h−1 during mixotrophic and heterotrophic growth regimes respectively. Stable, long‐term chemostat growth of Galdieria sp. RTK371 was achieved during photoautotrophic, mixotrophic and heterotrophic growth regimes. During periods of ammonium limitation, Galdieria sp. RTK371 increased its intracellular carbohydrate content (up to 37% w/w). In contrast, biomass grown in ammonium excess was composed of up to 65% protein (w/w). Results from this study demonstrate that the growth of Galdieria sp. RTK371 can be manipulated during continuous cultivation to obtain desired biomass and product yields over long cultivation periods.
Reverse thinking: Tumor nutritional therapy
Authors: Ding Binbin , Ma Ping'an , Kheraif Abdulaziz A. Al , Lin Jun
Published: July 2024

Tumor cells often exhibit metabolic abnormalities to meet the needs of rapid proliferation, and targeting tumor metabolism has become one of the effective strategies for cancer treatment. However, most of the current methods targeting metabolism focus on inhibiting hyperactivated metabolic pathways, hindering their further application. A recent innovative work, proposed a nutrient‐based strategy to reactivate metabolism for tumor therapy by targeting suppressed metabolic pathways. This approach through delivering nutrients to tumor cells directly using nanotechnology indicates that specific nutrients can serve as potent activators of metabolic pathways. As a new direction along the reverse thinking, this study suggests that this nutrient‐based metabolism reactivation strategy will inspire broad applications in the treatment of other diseases associated with metabolic disorders, besides tumor.
Phase I study of TQB3602, an oral proteasome inhibitor, in relapsed and refractory multiple myeloma
Authors: Tang Wenjiao , Li Yan , Zhang Li , Zhong Xushu , Liang Qiushi , Zheng Yuhuan , Liu Yuzhang , Wang Yafei , Wang Xunqiang , Zeng Yun , Fang Baijun , Zheng Li , Niu Ting
Published: July 2024

Objective

TQB3602 is a novel orally bioavailable proteasome inhibitor. This study is the first‐in‐human phase I clinical trial to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of TQB3602 in relapsed/refractory multiple myeloma (RRMM).

Methods

This is a multicenter phase I clinical trial consisting of the 3+3 dose‐escalation phase and dose expansion phase. Patients with MM who have received ≥2 prior antimyeloma therapies were enrolled. TQB3602 is administered at a dose of 0.5~7mg on days 1, 8, 15 in 28‐day cycle.

Results

Twenty‐five RRMM patients who relapsed or failed ≥2 lines of therapies were enrolled in the dose escalation phase. Two patients in the 7.0 mg dose group developed dose‐limiting toxicity events (one with grade 2 peripheral neuropathy [PN] complicated by pain and one with diarrhea and abdominal pain), leading to a maximum tolerated dose of 6.0 mg. Any‐grade adverse events (AEs) occurred in 24 (96.0%) patients, while grade ≥3 AEs occurred in 13 (52.0%). The most common grade ≥3 AEs was anemia (6, 24.0%). The incidence rate of PN was 16% with no grade ≥3 PN occurred. TQB3602 was rapidly absorbed, resulting in a time‐to‐plasma peak concentration of 0.8–1.5 h. The mean half‐life was approximately 82 h. The AUClast and Cmax were approximately 1.9 times higher on day 15 than on day 1. Among 22 response‐evaluable patients, 63.7% achieved stable disease or better.

Conclusions

TQB3602 is well tolerated, with a favorable neurotoxicity profile, and has shown preliminary efficacy in patients with RRMM. The anticipated therapeutic dose was 6 mg and was adopted for an ongoing dose‐expansion phase.
Synthesis, Antimicrobial ‐ Cytotoxic Evaluation, and Molecular Docking Studies of Quinolin‐2‐one Hydrazones Containing Nitrophenyl or Isonicotinoyl/Nicotinoyl Moiety
Authors: Doan Nam Q. H. , Tran Hoan N. , Nguyen Nhu T. M. , Pham Thu M. , Nguyen Quyen D. K. , Vu Thanh‐Thao
Published: July 2024

By applying the hybrid molecular strategy, in this study, we reported the synthesis of fifteen quinolin‐2‐one hydrazones containing nitrophenyl or nicotinonyl/isonicotinoyl moiety, followed by in vitro and in silico evaluations of their potential antimicrobial and anticancer activities. In vitro antimicrobial evaluation of the target compounds on seven pathogenic strains, applying the broth microdilution method, revealed that compound 4a demonstrated the most potential antifungal activity against C. albicans (MIC 512 μg mL−1) and C. krusei (MIC 128 μg mL−1). In vitro cytotoxic evaluation of the target compounds on three human cancer cell lines, employing the MTT method, suggested that compound 5c exhibited the most potential cytotoxicities against HepG2 (IC50 10.19 μM), A549 (IC50 20.43 μM), and MDA‐MB‐231 (IC50 16.82 μM) cells. Additionally, molecular docking studies were performed to investigate the binding characteristics of compounds 4a and 5c with fungal lanosterol 14α‐demethylase and human topoisomerase I–II, respectively, thereby contributing to the elucidation of their in vitro antifungal and cytotoxic properties. Furthermore, compounds 4a and 5c, via SwissADME prediction, could exhibit favorable physicochemical and pharmacokinetic properties. In conclusion, this study provides valuable insights into the potential of quinolin‐2‐one hydrazones as promising candidates for the development of novel antimicrobial and anticancer agents in the future.
A 64‐year‐old male with primary diffuse renal large B‐cell non‐Hodgkin lymphoma: A rare case report
Authors: Haydar Hasan , Sleiay Mouhammed , Alabdullah Hadi , Al‐alloush Rouba , Al_alloush Nour , Lutfi Mohamad Yasin , Youssef Simon , Hamsho Suaad
Published: July 2024

Key Clinical Message

In the context of lymphoma, it is of paramount importance to perform subsequent Positron Emission Tomography‐Computed Tomography (PET‐CT) scans to ensure the comprehensive eradication of neoplasms.

Primary renal diffuse tumors constitute less than 1% of all renal neoplasms. Among these, diffuse renal large B‐cell lymphoma is an exceedingly rare extranodal lymphoma. A 64‐year‐old male presented to the Department of Urology with complaints of persistent left flank discomfort for a duration of 2 weeks. Additionally, he reported generalized weakness, fatigue, and symptoms indicative of lower urinary tract obstruction, such as discomfort in the left testicle and dysuria. Ultrasound imaging revealed an echogenic structure with thickened, reactive walls and a turbid fluid core, located in the left flank, proximal to the lower pole of the kidney. This structure was subsequently identified as diffuse renal large B‐cell lymphoma. For the diagnosis of large B‐cell lymphomas, it is imperative that a proficient hematopathologist performs a comprehensive examination of the tumor tissue, preferably utilizing an excisional biopsy. The categorization of lymphoma requires specialized tests such as immunohistochemistry, flow cytometry, fluorescence in situ hybridization (FISH), and molecular testing. In instances where a renal mass is detected, healthcare professionals should consider performing a biopsy. In lymphoma cases, follow‐up Positron Emission Tomography‐Computed Tomography (PET‐CT) scans are crucial to confirm the complete eradication of the tumor.
Complex hidradenitis suppurativa on a background of long‐standing Crohn's disease requiring radical pelvic and perineal reconstruction: A case report
Authors: Forder Bea Harris , Nistor Sabina , Mykula Roman , Bignell Mark , Soleymani majd Hooman
Published: July 2024

Key Clinical Message

A surgical MDT approach to high‐complexity surgeries can allow maximal resection in order to achieve disease control and excellent functional outcomes, as demonstrated here for a case of hidradenitis suppurativa in a patient with Crohn's disease.

Hidradenitis suppurativa is an autoimmune disease characterized by abscess and fistula formation with purulent discharge in intertriginous zones, and is associated with inflammatory bowel disease. We present the case of a patient with severe ongoing hidradenitis suppurativa causing osteomyelitis and affecting the perineum, on a background of Crohn's disease previously treated with panprotocolectomy and permanent ileostomy. The hidradenitis suppurativa was having a severe impact on the patient's quality of life, and she had failed to respond to conservative management. The patient opted for a radical two‐step procedure: first her coccyx and sacrum were removed. The second step was a radical bilateral anterior vulvectomy and posterior vaginectomy, with preservation of the uterine body and cervix. An anterolateral thigh flap was used to reconstruct the perineum. This complex procedure required the expertise of multiple surgical specialties, including plastic, general, spinal, and gynecological oncology surgeons to achieve maximal disease resection, minimizing the risk of recurrence.
Nondestructive Identification of Wheat Seed Variety and Geographical Origin Using Near‐Infrared Hyperspectral Imagery and Deep Learning
Authors: Sharma Apurva , Singh Tarandeep , Garg Neerja Mittal
Published: July 2024

Seed purity assurance is an important aspect of maintaining the quality standards of wheat seeds. It relies significantly on quality parameters, like varietal classification and geographical origin identification. Hyperspectral imaging (HSI) has emerged as an advanced nondestructive technique to determine various quality parameters. In recent years, several studies have utilized HSI for varietal classification, although a limited number of varieties were considered. Additionally, no attention has been paid to determining the geographical origin of wheat seeds. To address these gaps, two separate experiments were performed for varietal classification and geographical origin identification. The seeds from 96 varieties grown across 5 different agricultural regions in India were collected. Hyperspectral images of wheat seeds were acquired in the wavelength ranging 900–1700 nm. The spectral reflectance values were obtained from the region of interest (ROI) corresponding to each seed. Subsequently, the deep learning models (convolutional neural networks [CNNs]) were established and compared with two conventional algorithms, including support vector machines (SVMs) and K‐nearest neighbors (KNNs). The experimental results indicated that the proposed CNN models outperformed the SVM and KNN models, achieving an overall accuracy of 94.88% and 99.02% for varietal classification and geographical origin identification, respectively. These results demonstrate that HSI combined with deep learning has the potential to accurately classify a large number of wheat varieties. Moreover, HSI can be used to precisely identify the geographical origins of wheat seeds. This study provides an accurate and nondestructive method that can assist in breeding, quality evaluation, and the development of high‐quality wheat seeds.
Effect of Sodium−Glucose Co‐Transporter‐2 Inhibitor on Estimated Plasma Volume in a Patient With Heart Failure With Reduced Ejection Fraction and a Patient With Heart Failure With Preserved Ejection Fraction
Authors: Taťána Andreasová , Filip Málek
Published: July 2024

Background

The increased diuresis after sodium−glucose cotransporter 2 inhibitor (SGLT2i) was associated with a reduction of the estimated plasma volume (ePV) in type 2 diabetic patients.

Hypothesis

We hypothesized that the early effect of SGLT2i on ePV may be monitored by the change of biomarkers of hemoconcentration.

Patients and Methods

We analyzed the early‐ and long‐term effect of SGLT2i empagliflozin on the ePV as assessed by biomarkers of hemoconcentration in a nondiabetic patient with heart failure and reduced ejection fraction (HFrEF) and a nondiabetic patient with heart failure and preserved ejection fraction (HFpEF). The ePV was calculated from hemoglobin and hematocrit levels by Duarte formula and ePV change was calculated by Strauss formula.

Results

The ePV change was −22.56% between baseline and 1 month, and −37.60% between baseline and 12 months follow‐up in a patient with HFrEF, and −6.18% and −16.40% in a patient with HFpEF, respectively.

Conclusion

The early effect of SGLT2i on ePV in patients with heart failure may be monitored by biomarkers of hemoconcentration.
Implementation of flow cytometry testing on rare matrix samples: Special considerations and best practices when the sample is unique or difficult to obtain
Authors: Devitt Katherine A. , Kern Wolfgang , Kajstura Malgorzata A. , Holl Eda K. , Hays Amanda L. , Hedley Benjamin D. , Gonneau Christèle , Jellison Evan R. , McCloskey Thomas W. , Mishra Shruti , Rebeles Jennifer , Ouseph Madhu M.
Published: July 2024

The publication of Clinical and Laboratory Standards Institute's guideline H62 has provided the flow cytometry community with much‐needed guidance on development and validation of flow cytometric assays (CLSI, 2021). It has also paved the way for additional exploration of certain topics requiring additional guidance. Flow cytometric analysis of rare matrices, or unique and/or less frequently encountered specimen types, is one such topic and is the focus of this manuscript. This document is the result of a collaboration subject matter experts from a diverse range of backgrounds and seeks to provide best practice consensus guidance regarding these types of specimens. Herein, we define rare matrix samples in the setting of flow cytometric analysis, address validation implications and challenges with these samples, and describe important considerations of using these samples in both clinical and research settings.
Unraveling the Surface‐Diffusion Charge Contribution Studies of Zeolitic‐Imidazolate‐Frameworks‐Based Core–Shell Structure for High‐Performance Hybrid Supercapacitors
Authors: Mansi  , Dubey Prashant , Shrivastav Vishal , Hołdyński Marcin , Sundriyal Shashank , Tiwari Umesh K. , Deep Akash
Published: July 2024

In this work, zeolitic imidazolate frameworks (ZIF‐8@ZIF‐67)‐based core–shell structure as a supercapacitor electrode is synthesized. The core–shell structure is designed with a ZIF‐8 core, onto which a ZIF‐67 shell is grown. This unique architecture aims to expedite the diffusion of electrolyte ions, facilitate inner–outer metal ion electron transfer, and consequently enhance electrochemical performance. When used as an active electrode material, the material delivers 263.43 F g−1 of capacitance at 0.5 A g−1 of discharge rate. The core–shell structure exhibits 68% of surface contribution toward the total capacitance. At the scan rate of 50 mV s−1, the sample almost exhibits equal contribution of diffusion and surface charge contribution. Further an asymmetric supercapacitor (ASC) device is assembled, featuring a ZIF‐8@ZIF‐67 core–shell metal‐organic framework (MOF) as a positive electrode and waste‐tissue‐paper‐derived activated carbon as negative electrode using 1 m H2SO4 aqueous electrolyte. The ASC device delivers an energy density of 38.4 Wh kg−1 at the power density of 0.8 kW kg−1, along with long cycle life of 95.2% after an extensive 10 000 cycles. In this work, the significance of the ZIF‐based core–shell structure in advancing supercapacitor technology, which further can be extended to multiple core–shell structure and other MOF combination, is highlighted.
Reactive oxygen‐scavenging polydopamine nanoparticle coated 3D nanofibrous scaffolds for improved osteogenesis: Toward an aging in vivo bone regeneration model
Authors: Miszuk Jacob , Hu Jue , Wang Zhuozhi , Onyilagha Obiora , Younes Hammad , Hill Collin , Tivanski Alexei V. , Zhu Zhengtao , Sun Hongli
Published: July 2024

Tissue engineered scaffolds aimed at the repair of critical‐sized bone defects lack adequate consideration for our aging society. Establishing an effective aged in vitro model that translates to animals is a significant unmet challenge. The in vivo aged environment is complex and highly nuanced, making it difficult to model in the context of bone repair. In this work, 3D nanofibrous scaffolds generated by the thermally‐induced self‐agglomeration (TISA) technique were functionalized with polydopamine nanoparticles (PD NPs) as a tool to improve drug binding capacity and scavenge reactive oxygen species (ROS), an excessive build‐up that dampens the healing process in aged tissues. PD NPs were reduced by ascorbic acid (rPD) to further improve hydrogen peroxide (H2O2) scavenging capabilities, where we hypothesized that these functionalized scaffolds could rescue ROS‐affected osteoblastic differentiation in vitro and improve new bone formation in an aged mouse model. rPDs demonstrated improved H2O2 scavenging activity compared to neat PD NPs, although both NP groups rescued the alkaline phosphatase activity (ALP) of MC3T3‐E1 cells in presence of H2O2. Additionally, BMP2‐induced osteogenic differentiation, both ALP and mineralization, was significantly improved in the presence of PD or rPD NPs on TISA scaffolds. While in vitro data showed favorable results aimed at improving osteogenic differentiation by PD or rPD NPs, in vivo studies did not note similar improvements in ectopic bone formation an aged model, suggesting that further nuance in material design is required to effectively translate to improved in vivo results in aged animal models.
Development of a composite using calcined bone powder and silane cross‐linked alginate as bone substitute material
Authors: Tanaka Shigeo M.
Published: July 2024

Calcined bone is an attractive natural material for use as a bone substitute because of its cost‐effectiveness and high biocompatibility, which are comparable to that of synthetic hydroxyapatite. However, the calcination process has significantly weakened the mechanical properties. In this study, a composite of calcined bovine bone powder reinforced with silane cross‐linked alginate was prepared to assess its biocompatibility, osteoconductivity, and mechanical compatibility as a bone substitute material. Culture studies with osteoblast‐like cells (MC3T3‐E1) showed no cytotoxicity toward the composite and exhibited general cell proliferative properties in its presence. In contrast, the composite reduced the alkaline phosphatase activity of osteoblasts but led to significant noncellular apatite deposition on the surface. In addition, quasi‐static compression tests of the composite revealed mechanical properties comparable to those of human cancellous bone. The mechanical properties remained stable under wet conditions and did not deteriorate significantly even after 2 weeks of immersion in simulated body fluid at 37°C. The results show that this composite, composed of calcined bone powder and silane cross‐linked alginate, is a promising bone substitute material with biocompatibility, osteoconductivity, and mechanical compatibility.
On the wing: Morphological variation in the osteology of Mediterranean, Near Eastern, and European Anatidae (excluding Anserinae)
Authors: Haruda Ashleigh , Mazzucato Camilla , Yeomans Lisa
Published: July 2024

Accurate identification of waterfowl bones in archaeological and fossil assemblages has potential to unlock new methods of past environmental reconstruction, as species have differing habitat preferences and migration patterns. Therefore, identifying the presence of avian species with different ecological niches is key to determining past environments and ultimately how prehistoric people responded to climatic and environmental realignments. However, the identification of osteological remains of waterbirds such as ducks to species level is notoriously challenging. We address this by presenting a new two‐dimensional geometric morphometric protocol on wing elements from over 20 duck species and test the utility of these shape data for correct species identification. This is an ideal starting point to expand utilization of these types of approaches in avifaunal research and test applicability to an extremely difficult taxonomic group.
Interannual variability of the occurrence frequency of the stronger Kunming quasi‐stationary front in winter
Authors: Du Xiaorui , Dai Haocheng , Cao Jie , Tao Yun , Yu Jiantong
Published: July 2024

Using ERA5 reanalysis data, this study explores the interannual variability of the occurrence frequency of the stronger Kunming quasi‐stationary front during in winter over the period 1980–2021 and the main causes of the variability. The results indicate that the occurrence frequency is significantly modulated on interannual timescales by southwesterly anomalies over the warmer region west of 103° E and northeasterly anomalies over the colder region east of 106° E. When the stronger southwesterly anomalies over the warmer region are comparable with stronger northeasterly anomalies over the colder region, the inhomogeneities of horizontal convergence and diabatic heating are strengthened near the frontal zone. This anomalous circulation causes a higher‐than‐normal occurrence frequency of the stronger Kunming quasi‐stationary front in winter. The East Asian winter monsoon (EAWM) and circumglobal teleconnection (CGT) are the two most important controls on the interannual variability of the occurrence frequency of the stronger Kunming quasi‐stationary front. Both the CGT and EAWM modulate the inhomogeneities of horizontal convergence and diabatic heating on the west flank of the front, and the EAWM further regulates diabatic heating over the east flank of the front.
Utilization and impact of esophageal string testing in children with eosinophilic esophagitis: A 1 year experience
Authors: Quinn Laura A. , Andrews Rachel , Bauer Maureen , Nguyen Nathalie
Published: July 2024

The 1‐h esophageal string test (EST) is a minimally invasive test that can be used to monitor eosinophilic esophagitis (EoE) disease activity and guide treatment without endoscopy. We aimed to describe the real‐world utilization and impact of EST on the care of children with EoE over the first year this was used at our center. Between 12/1/2022 and 11/30/2023, 39 ESTs were successful in 45 attempts (87% completion rate) in 31 patients. Five patients underwent multiple ESTs. Adverse events during the EST included vomiting. Reasons for failure to complete the EST (13%, n = 6) were patients could not swallow the capsule (n = 5) and vomiting (n = 1). EST was used to assess EoE without the need for endoscopy in 95% (n = 37) of cases. Treatment approach varied based on whether the EST indicated active (38.5%) or inactive (61.5%) EoE. The EST is a well‐tolerated minimally invasive disease monitoring tool for patients with EoE.
Jaguar predation on domestic horses in the dry forest of northwestern Costa Rica
Authors: Morera Brayan , Montalvo Víctor , Moya Jairo , Obando Javier , Sáenz‐Bolaños Carolina , Fuller Todd K. , Carrillo Eduardo
Published: July 2024

Depredation of domestic horses (Equus caballus) by jaguars (Panthera onca) is an example of human–wildlife conflict that has not received much attention. We monitored spatio‐temporal activity and distribution of horses in a 2.64‐km2 fenced area in the dry forest of northwestern Costa Rica in response to 16 jaguar killings of horses during January‐November 2017. We monitored 4 horses (2 males, 2 females) equipped with global positioning system transmitters from February‐September 2018 to identify daily and seasonal patterns of use of cover types and a water source by horses. We then compared these results to the previous locations where jaguars killed horses to identify the circumstances under which horses seemed more vulnerable to jaguar predation. Based on 1,693 locations, horses spent most time in grassland (92%) rather than forest and edge vegetation (8%) and used a core area of 0.74 km2 (kernel density estimation) to 0.86 km2 (minimum convex polygon). Of 16 horse predation events by jaguars, 9 events (56%) occurred in grasslands, 4 in forested areas (25%), and 3 in the forest edge (19%), indicating predation events occurred disproportionately from expected counts based on horse use of vegetation. The predation sites were characterized by a higher proportion of edge and a lower proportion of forest compared to a random points. We suggest that when horses explored areas near the edge of forested areas, the chances of being preyed on by jaguars increased.