bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pan‐cancer analysis of TIM‐3 transcriptomic expression reveals high levels in pancreatic cancer and interpatient heterogeneity
Authors: Lim Jungah , Kurzrock Razelle , Nishizaki Daisuke , Miyashita Hirotaka , Adashek Jacob J. , Lee Suzanna , Pabla Sarabjot , Nesline Mary , Conroy Jeffrey M. , DePietro Paul , Lippman Scott M. , Kato Shumei 
Published: December 2023

AbstractBackgroundT‐cell immunoglobulin and mucin domain‐containing protein 3 (TIM‐3), an immune checkpoint receptor, dampens immune function. TIM‐3 antagonists have entered the clinic.MethodsWe analyzed TIM‐3 transcriptomic expression in 514 diverse cancers. Transcript abundance was normalized to internal housekeeping genes and ranked (0–100 percentile) to a reference population (735 tumors; 35 histologies [high≥75 percentile rank]). Ninety tumors (17.5%) demonstrated high TIM‐3 expression.ResultsTIM‐3 expression varied between and within tumor types. However, high TIM‐3 expression was more common in pancreatic cancer (20/55 tumors, 36.4%; odds ratio, 95% confidence interval (pancreatic vs. other tumors) = 3.176 (1.733–5.818; p < 0.001, multivariate]). High TIM‐3 also significantly and independently correlated with high PD‐L1 (p = 0.014) and high CTLA‐4 (p < 0.001) transcriptomic expression (multivariate).ConclusionsThese observations indicate that TIM‐3 RNA expression is heterogeneous, but more common in pancreatic cancer and in tumors exploiting PD‐L1 and CTLA‐4 checkpoints. Clinical trials with patient selection for matched immune‐targeted combinations may be warranted.
Exploration of treatment‐free remission in CML, based on molecular monitoring
Authors: Zhang Zhao , Zhou Xianghui , Zhou Xin , Cheng Zhipeng , Hu Yu 
Published: December 2023

AbstractBackgroundTypical chronic myelogenous leukemia (CML) is a myeloproliferative neoplasm caused by t(9; 22)(q34; q11) translocation. This chromosomal translocation forms the BCR::ABL1 fusion gene. The tyrosine kinase encoded by the BCR::ABL1 is considered to be the main pathogenic diver. BCR::ABL1 is not only a therapeutic target, but also a monitoring target. Monitoring of BCR::ABL1 reveals the progression of the disease and guides the next treatment. Now for CML, the target of treatment has been focused on treatment‐free remission (TFR).MethodsWe conducted a literature review of current developments of treatment‐free remission and molecular monitoring methods.ResultsMore effective and sensitive CML monitoring methods such as digital droplet PCR (ddPCR) and next generation sequencing (NGS) have further studied the measurable residual disease (MRD) and clonal heterogeneity, which provides strong support for the exploration of TFR. We discussed some of the factors that may be related to TFR outcomes at the molecular level, along with some monitoring strategies.ConclusionCurrently, predictive indicators for treatment‐free remission outcomes and recurrence are lacking in clinical practice. In future, treatment‐free remission research should focus on combining the clinical indicators with molecular monitoring and biological markers to personalize patient conditions and guide clinicians to develop individualized treatment plans, so that more patients with CML can achieve safer and stabler treatment‐free remission.
Selective Oxidation of 5‐Hydroxymethylfurfural to 2,5‐Diformylfuran in Biphasic Media using Immobilized Galactose Oxidase: Proof of Concept and Limitations
Authors: Milić Milica , Byström Emil , Domínguez de María Pablo , Kara Selin 
Published: December 2023

AbstractThe oxidation of 5‐hydroxymethylfurfural (HMF) to 2,5‐diformylfuran (DFF) is a key reaction in valorizing biomass. DFF is hardly soluble in water, while HMF is often obtained from biorefineries in crude wet organic fractions. Thus, the reaction is challenging for both biocatalysis performed in aqueous media, and for chemocatalysis where the presence of water often results in catalyst poisoning. Galactose oxidase (GalOx) can selectively oxidize HMF to DFF and displays promising activity in aqueous‐organic media. In this study, GalOx was immobilized on ten carriers, assessing the immobilization yield, activity, and stability. Covalently immobilized GalOx catalyzed the oxidation of HMF to DFF in neat and water‐saturated EtOAc, and in biphasic systems of various water contents. At 50 % v/v H2O, the reaction was conducted at a semi‐preparative scale (50 mL) with no adverse effect on DFF yield. Some limitations arise, such as enzyme deactivation, and adsorption of DFF to the support, particularly in the aqueous fraction. Future options to upgrade the route may include designed stable enzymes under the presence of HMF/DFF, and the setup of microaqueous systems where DFF adsorption is minimized. The use of wet EtOAc media would be a promising approach in future biorefineries employing inexpensive crude wet organic fractions.
Mn(III) O^N^O Complexes as Water‐tolerant and Environmentally Benign Catalysts for Polyurethane Foam Synthesis
Authors: Ocansey Edward , Sala Oliver , Kamm Marina , Joost Maximilian , Bokern Stefan , Rominger Frank , Hashmi A. Stephen K. , Mormul Jaroslaw , Schaub Thomas 
Published: December 2023

AbstractPolyurethanes are synthesized on industrial scale by the reaction of diisocyanates with diols in the presence of catalysts which are commonly based on tin complexes and amines. However, due to the toxicity and volatility of these tin catalysts and amines, there is the need to develop new catalysts that are more environmentally benign. Herein, we report the synthesis of O^N^O pincer‐ligated Mn(III) and Fe(III) complexes that serve as suitable catalysts for urethane formation and are stable to hydrolysis as predicted by computations and observed experimentally. The O^N^O pincer scaffold is vital to the activity of these catalysts, simultaneously ensuring increased solubility in the reaction medium as well as providing a stable framework upon dissociation of co‐ligands in the catalytic cycle. In silico mechanistic investigations for urethane formation show that the stabilization of active species in square‐planar geometries enabled by these O^N^O ligands permit the simultaneous coordination of alcohol and isocyanate in suitable configuration at the metal center.
Early detection of Kentucky bluegrass and perennial ryegrass responses to drought stress by measuring chlorophyll fluorescence parameters
Authors: Itam Michael , Hall David , Kramer David , Merewitz Emily 
Published: December 2023

AbstractKentucky bluegrass (Poa pratensis L.; drought resistant) and perennial ryegrass (Lolium perenne L.; drought sensitive) are economically important grass species contrasting in drought stress resistance. This study determined the optimal chlorophyll fluorescence parameters to indicate drought incidence and whether the parameters differentiate intra‐ and interspecies variations in drought stress. For each species, nine cultivars were exposed to well‐watered or drought (water withheld) conditions in growth chambers containing high‐throughput photosynthetic imagers to track real‐time responses of maximum quantum efficiency of photosystem II (Fv/Fm), quantum yield of photosystem II (ΦII), non‐photochemical quenching (NPQ), energy‐dependent quenching (qE), and photoinhibition‐associated quenching (qI). Soil moisture content and relative water content of leaf tissues were evaluated. Due to drought, Fv/Fm and ΦII decreased for cultivars of both species but earlier for perennial ryegrass compared to Kentucky bluegrass. The NPQ, qI, and qE values exhibited more dynamic and earlier changes due to drought compared to Fv/Fm and ΦII and allowed for early, mid, and late drought responses to be illustrated. Drought induced an increase in NPQ, qI, and qE values, which corresponded to activation of photoprotection mechanisms, and was exhibited earlier for perennial ryegrass compared to Kentucky bluegrass. As the drought treatment progressed, a decrease or stabilization of low values of NPQ, qI, and qE was observed, and the lowest values were associated with the most drought‐sensitive cultivars. These results indicate important stress tolerance protection mechanisms for grass species and will broadly impact basic and applied grass research as a nondestructive phenotyping tool.
CALCRL knockdown suppresses cancer stemness and chemoresistance in acute myeloid leukemia with FLT3‐ITD and DNM3TA‐R882 double mutations
Authors: Tang Shanhao , Zhu Huiling , Sheng Lixia , Mu Qitian , Wang Yi , Xu Kaihong , Zhou Miao , Xu Zhijuan , Wu An , Ouyang Guifang 
Published: December 2023

AbstractAcute myeloid leukemia (AML) patients with FLT3 internal tandem duplication (FLT3‐ITD) and DNA methyltransferase 3A (DNMT3A) R882 double mutations had a worse prognosis compared with AML with FLT3‐ITD or DNMT3A R882 single mutation. This study was designed to explore the specific role of Calcitonin Receptor Like (CALCRL) in AML with FLT3‐ITD and DNMT3A R882 double mutations. MOLM13 cells were transduced with CRISPR knockout sgRNA constructs to establish the FTL3‐ITD and DNMT3A‐R882 double‐mutated AML cell model. Quantitative real‐time PCR and Western blot assay were carried out to examine corresponding gene and protein expression. Methylation of CALCRL promoter was measured by methylation‐specific PCR (MSP). Cell viability, colony formation, flow cytometry, and sphere formation assays were conducted to determine cell proliferation, apoptosis, and stemness. MOLM13 cells were exposed to stepwise increasing concentrations of cytarabine (Ara‐C) to generate MOLM13/Ara‐C cells. An in vivo AML animal model was established, and the tumor volume and weight were recorded. TUNEL assay was adopted to examine cell apoptosis in tumor tissues. DNMT3A‐R882 mutation upregulated the expression of CALCRL while downregulated the DNA methylation level of CALCRL in MOLM13 cells. CALCRL knockdown greatly inhibited cell proliferation, promoted apoptosis and repressed cell stemness, accompanied with the downregulated Oct4, SOX2, and Nanog in DNMT3A‐R882‐mutated MOLM13 cells and MOLM13/Ara‐C cells. Furthermore, CALCRL knockdown restricted tumor growth and the chemoresistance of AML in vivo, as well as inducing cell apoptosis in tumor tissues. Together, these data reveal that CALCRL is a vital regulator of leukemia cell survival and resistance to chemotherapy, suggesting CALCRL as a promising therapeutic target for the treatment of FTL3‐ITD and DNMT3A‐R882 double‐mutated AML.
Everolimus inhibits hepatoblastoma by inducing autophagy‐dependent ferroptosis
Authors: Huang Haijin , Yan Jinlong , Xu Xianyun , Feng Yanping , Liu Haijin , Liu Jianping , Xie Mingfeng , Chen Leifeng , Xiang Deng , Peng Wei , Zeng Linshan , Zeng Yong , Chen Feng , Zhang Shouhua , Liu Qian 
Published: December 2023

AbstractEverolimus, a known inhibitor of the mammalian target of rapamycin (mTOR), has shown uncertain efficacy in treating hepatoblastoma. This study delves into the potential anti‐hepatoblastoma properties of everolimus and its intricate relationship with autophagy and ferroptosis, both in vitro and in vivo. In vivo, tumor tissue from hepatoblastoma patient and human hepatoblastoma cell line HuH‐6 were xenografted into nude mice to establish xenograft models for observing the effect of everolimus on tumor growth. In vitro, HuH‐6 cells were cultured to evaluate the anti‐hepatoblastoma activity of everolimus. Transmission electron microscopy and microtubule‐associated proteins 1 light chain 3 (LC3), beclin 1, and p62 protein expressions were employed to investigate autophagy. Additionally, indicators of cell apoptosis, reactive oxygen species (ROS) and proteins associated with ferroptosis were measured to evaluate ferroptosis. The results demonstrate that everolimus treatment effectively induced the formation of autophagosomes in hepatoblastoma cells, upregulated the LC3II/I ratio and beclin 1 expression, and downregulated p62 expression, indicating an enhanced autophagy level both in vitro and in vivo. Furthermore, everolimus treatment induced cell apoptosis, increased ROS level, elevated concentrations of malondialdehyde, 4‐hydroxynonenal, and iron content, while reducing the ratio of glutathione/oxidized glutathione, and downregulating the protein expression of glutathione peroxidase 4 and solute carrier family 7 member 11, suggesting its ability to induce ferroptosis in hepatoblastoma cells. Importantly, the induction of ferroptosis by everolimus was significantly reversed in the presence of autophinib, an autophagy inhibitor, indicating the autophagy‐dependent of everolimus‐induced ferroptosis. Taken together, these findings suggest that everolimus holds promise as an effective anti‐hepatoblastoma drug, with its mechanism of action potentially involving the induction of autophagy‐dependent ferroptosis in hepatoblastoma cells.
Tetrahedral serial multiview microscopy and image fusion for improved resolution and extent in stained zebrafish embryos
Authors: Kroll Johanna B. , Cha Anna , Oyler‐Yaniv Alon , Lambert Talley , Swinburne Ian A. , Murphy Andrew , Megason Sean G. 
Published: December 2023

AbstractBackgroundSpatial mapping on the single‐cell level over the whole organism can uncover roles of molecular players involved in vertebrate development. Custom microscopes have been developed that use multiple objectives to view a sample from multiple views at the same time. Such multiview imaging approaches can improve resolution and uniformity of image quality as well as allow whole embryos to be imaged (Swoger et al., Opt Express, 2007;15(13):8029). However, multiview imaging is highly restricted to specialized equipment requiring multiple objectives or sample rotation with automated hardware.ResultsOur approach uses a standard single‐objective confocal microscope to perform serial multiview imaging. Multiple views are imaged sequentially by mounting the fixed sample in an agarose tetrahedron that is manually rotated in between imaging each face. Computational image fusion allows for a joint 3D image to be created from multiple tiled Z‐stacks acquired from different angles. The resulting fused image has improved resolution and imaging extent.ConclusionWith this technique, multiview imaging can be performed on a variety of common single‐objective microscopes to allow for whole‐embryo, high‐resolution imaging.
Application of ionic liquids and various carbon materials in reference electrodes with carbon paste‐based transducers
Authors: Kuczak Julia , Woszczyk Wiktoria , Pazik Małgorzata , Li Lee Chuan , Mohd Sahfani Mohd Nor Hafizuddin Bin , Ling Chin Kit , Grabowska‐Jadach Ilona , Toczyłowska‐Mamińska Renata , San H'ng Paik , Górski Łukasz 
Published: December 2023

AbstractIn this article it is proved that carbon pastes with ionic liquids (ILs) are a promising material for transducers of reference electrodes, which favors their miniaturization. Two ILs were used: 1‐(2‐hydroxyethyl)‐3‐methylimidazolium bis(trifluoromethylsulfonyl)imide (IL1) and 1‐(2‐methoxyethyl)‐3‐methylimidazolium bis(trifluoromethylsulfonyl)imide (IL2). They acted both as a binder of carbon paste and potential‐determining component. ILs were also used in polymeric membrane of reference electrodes what ensured continuity of IL phase between carbon paste and the polymeric membrane and resulted in enhancement of electrode potential stability. It was shown that application of IL as a carbon paste binder is superior to conventional plasticizer and allows for significant increase of reference electrode potential stability. Different types of carbon materials were also tested during research: commercialy available graphite powder and graphene oxide obtained from waste biomass – palm kernel shells. It was observed that both the type of carbon paste material and IL influences reference electrode work parameters. Utilization of IL with less lipophilic cation resulted in higher potential stability of the reference electrodes. Application of graphite paste‐based transducers resulted in higher potential stability of reference electrodes in sodium perchlorate and TMA chloride solutions while using palm kernel shell graphene oxide paste – based transducers caused enhancement of reference electrode long‐term potential stability. The results indicate biomass‐derived graphene oxide can be successfully applied as a construction material of reference electrode.
Application of palm oil frond activated carbon for biobattery electrodes
Authors: Akbar Muhammad Ilham , Zahirah Natasya , Utomo Yogi Mirza Pangestu , Risnawati Risnawati , Astuti Widi , Rohimsyah Fikan Mubarok , Triana Yunita 
Published: December 2023

AbstractThis study aims to investigate the effect of NaOH concentration and immersion time on the activation of carbon from the oil palm frond, specifically focussing on the surface morphology and characteristics as electrodes for biobattery application. Carbonization and NaOH activation are carried out at 0.5, 1, 1.5, 2, and 2.5 M at different immersion times of 12, 18, 24, 30, and 36 hour. Moreover, the activated carbon was analyzed with a scanning electron microscope to observe the morphology, and the Brunauer–Emett–Teller (method was used to measure the surface area of activated carbon). Furthermore, another outcome of this study is the development of a prototype biobattery. At 1 M, the optimal concentration of NaOH was observed, producing the highest surface area of 336.493 m2g−1 and an electric potential of 0.653 V. On the other hand, the optimal immersion time was 30 hour with the highest surface area of 396 808 m2g−1 and an electric potential of 0.902 V.
Learning losses during the COVID‐19 pandemic: Understanding and addressing increased learning disparities
Authors: Alejo Anna , Jenkins Robert , Yao Haogen 
Published: December 2023

AbstractA growing body of evidence has revealed the negative effects of COVID‐19‐induced school closures on learning, with the largest losses often observed among the most vulnerable children. Learning disparities widened due to six potential reasons related to marginalized children, who (a) were already behind even before the pandemic, (b) were more likely to experience longer school closures, (c) had limited access to and support on remote learning, (d) were less likely to receive supervision and learning support at home, (e) face greater obstacles to return to school, and (f) return to school systems that are less able to provide for their needs. To ensure all children—especially the most vulnerable—can catch up on missed learning, five urgent actions are needed for a RAPID learning recovery and acceleration: (a) Reach every child and keep them in school, (b) Assess learning levels regularly, (c) Prioritize teaching the fundamentals, (d) Increase the efficiency of instruction, and (e) Develop psychosocial health and wellbeing. Implementation of RAPID actions must be strengthened and supported by enabling systems to address the widening disparities in learning.
The rock mechanical relevance of anisotropy in tunnel design
Authors: Marcher Thomas 
Published: December 2023

AbstractThe assumption of an isotropic material behaviour is still common practice for tunnel design. Strictly speaking, this assumption is only valid if the influence of directional dependencies on the resulting deformations and stresses is marginal. In lithologies that have a high degree of anisotropy, such as shales and phyllites, the orientation characteristics of material properties such as strength and stiffness should be taken into account in order to avoid serious misinterpretations of the bearing capacity and deformation characteristic of the surrounding rock and the tunnel lining. The main focus is to accurately distinguish between the different types and terminology of anisotropy.
Tongue electrical impedance myography correlates with functional, neurophysiologic, and clinical outcome measures in long‐term oropharyngeal cancer survivors with and without hypoglossal neuropathy: An exploratory study
Authors: Hansen Nathan J. , Woodman Karin , Buoy Sheila , Mao Shitong , Barbon Carly E. A. , Lai Stephen Y. , Fuller C. David , Hutcheson Katherine A. , Sanchez Benjamin 
Published: December 2023

AbstractBackgroundThis pilot study analyzed correlations between tongue electrical impedance myography (EIM), standard tongue electromyography (EMG), and tongue functional measures in N = 4 long‐term oropharyngeal cancer (OPC) survivors.MethodsPatients were screened for a supportive care trial (NCT04151082). Hypoglossal nerve function was evaluated with genioglossus needle EMG, functional measures with the Iowa oral performance instrument (IOPI), and multi‐frequency tissue composition with tongue EIM.ResultsTongue EIM conductivity was higher for patients with EMG‐confirmed cranial nerve XII neuropathy than those without (p = 0.005) and in patients with mild versus normal EMG reinnervation ratings (16 kHz EIM: p = 0.051). Tongue EIM correlated with IOPI strength measurements (e.g., anterior maximum isometric lingual strength: r2 = 0.62, p = 0.020).ConclusionsTongue EIM measures related to tongue strength and the presence of XII neuropathy. Noninvasive tongue EIM may be a convenient adjunctive biomarker to assess tongue health in OPC survivors.
Relationship between bilirubin and systemic lupus erythematosus: A systematic review and meta‐analysis
Authors: Yu Yanxia , Wang Qiaoyu , Zhang Dongmei , Wu Weihua , Jiang Zheng 
Published: December 2023

AbstractAimsSystemic lupus erythematosus (SLE) is an autoimmune disease with a high prevalence worldwide. This study aimed to examine the correlation between serum bilirubin levels and SLE.MethodsThe Cochrane library, Embase, PubMed, and China National Knowledge Infrastructure (CNKI) databases were examined and assessed until March 2023. RevMan 5.3 software was utilized for the analysis of clinical trails.ResultsFive case‐control studies were chosen and incorporated, examining the levels of serum bilirubin in patients with SLE compared to healthy individuals, as well as in active SLE patients versus inactive ones, in different sexes and in SLE patients with or without lupus nephritis (LN). The results of this meta‐analysis demonstrated that serum bilirubin in healthy individuals were obviously increased compared to SLE patients (MD = 4.76; 95% CI, 3.15–6.38, p < .00001). Additionally, inactive SLE patients had higher levels of bilirubin than active SLE patients (MD = 3.15; 95% CI, 0.46–5.84, p = .02), and SLE patients without lupus nephritis had higher levels of serum bilirubin than those with lupus nephritis (MD = 4.91;95% CI, 2.87–6.95, p < .00001). Nevertheless, there were no disparities observed among SLE patients of varying sexes (MD = 0.34; 95% CI, −0.01 to 0.69, p = .06).ConclusionThe concentration of serum bilirubin may potentially be used as an indicator for estimating the advancement of SLE and reflecting the presence of kidney complications in individuals with SLE. Furthermore, more high quality studies were needed to identify these findings.
Trade war fallout: Exploring the altered landscape of US wooden furniture imports
Authors: Jiang Bowen , Muhammad Andrew 
Published: December 2023

AbstractWe examined the effects of the trade war on US wooden furniture imports by product category (kitchen, bedroom, other) and exporting source (e.g., China, European Union, Vietnam) using a two‐stage demand procedure and general nested demand framework. There were significant competitive relationships across exporting countries. However, when both trade creation and diversion were considered, competitive relationships either diminished or became complementary. Consequently, elimination of the trade‐war tariffs would increase imports from China but would also benefit countries like Vietnam. However, results indicate that imports from China would still be significantly less than pretrade war levels if the tariffs are eliminated.