bluuebunny/crossref_metadata_2025 huggingface dataset:
Study on the Strength and Deformation Characteristics of Coarse-Grained Soil under End-Restraint and End-Free (Microfriction) Conditions
Authors: Wang Yanli , Pan Jiajun , Zhang Hailong , Zhou Song , Xu Han
Published: October 2023

In this study, for triaxial compression testing in geotechnical engineering, large-scale triaxial shear tests of coarse-grained soil were performed under end-restraint and end-free (microfriction) conditions utilizing a large-scale triaxial shear apparatus and a self-developed microfriction load-transfer plate. Under end-restraint and end-free (microfriction) circumstances, the strength and deformation characteristics of the coarse-grained soil were investigated. Further, the effect of the end restraint on the stress–strain characteristics of the coarse-grained soil was analyzed. The findings showed that the coarse-grained soil’s stress–strain curves under the end-restraint and end-free (microfriction) conditions displayed both softening under low confining pressures and hardening under high confining pressures. However, the stress–strain curves’ tendency to soften under low confining pressures was more pronounced under the end-free (microfriction) condition. Due to the influence of the end constraint, the peak strength of the coarse-grained soil increased under the same confining pressure, although the increase was less than 10% when the specimen had the typical height-to-diameter ratio of 2 in the drained triaxial test. Meanwhile, the coarse-grained soil first displayed volumetric contraction under the low confining pressures, followed by volumetric dilation, and it displayed volumetric dilation under the high confining pressures. The volumetric contraction tendency of the coarse-grained soil was more pronounced in the first stages of shearing when the low confining pressures were present. As the shear increased, it became more obvious that the coarse-grained soil had a tendency to dilate under the end-free (microfriction) conditions. Throughout the shearing operation, the coarse-grained soil exhibited a high propensity toward shear contraction. The coarse-grained soil’s strength values were not greatly impacted by the end limitation, but the deformation parameters were. Under the end-restraint conditions, the deformation parameter increased significantly, while the strength parameter only changed slightly.
Periods and Processes of Oil and Gas Accumulation in the HZ-A Structure Double Paleogene Field, Pearl River Mouth Basin
Authors: Liu Jun , Peng Guangrong , Xu Leyi , Liu Pei , Xiong Wanlin , Luo Ming , Gao Xiang , Liu Xumin , Liang Haoran , Li Zhichao
Published: October 2023

The source of oil and gas and the stages of oil and gas accumulation in the “double-Paleo” field of the HZ-A structure in the Pearl River Mouth Basin are analyzed, and the spatiotemporal coupling relationship of the key conditions of oil and gas accumulation are discussed to reconstruct the process of oil and gas accumulation. Based on previous research results, which are based the characteristics of biomarker compounds, the oil and gas in the HZ-A structure double Paleogene field came from the Paleogene Wenchang Formation hydrocarbon source rocks in the HZ26 sub-sag. By means of the casting thin section identification and inclusion homogenization temperature measurement, this paper reveals the three major hydrocarbon accumulation periods and corresponding fluid charging types in the “double-Paleo” field of the HZ-A structure in the Pearl River Mouth Basin. The results show that 13.8–10 Ma is the charging period of low mature crude oil, 10–5.3 Ma is the charging period of mature crude oil, and from 5.3 Ma is the natural gas charging period. Based on actual geological, drilling, logging, and seismic data, the key conditions for hydrocarbon accumulation in the HZ-A structure “double-Paleo” field are sorted out; that is, the source conditions are characterized by high-quality lacustrine source rocks generating early oil and late gas and a near-source continuous hydrocarbon supply. The reservoir conditions are characterized by weathering and superposition of a fracture zone that transforms into a reservoir, and a large-scale sandstone rock mass that transforms into a reservoir. The caprock conditions are characterized by the stacking of several thin mudstones that form a seal and the combination of multiple lithologies that block hydrocarbon migration. The trap conditions are characterized by multistage uplift structure traps and fracture-lithology combination control traps. The transport conditions are characterized by multi-stage cross-bed transport of source-connected faults and lateral differential transport of shallow sand in deep fractures. Finally, oil and gas accumulation models of the HZ-A structure double Paleogene field were established, and the accumulation process was reconstructed. The overall process involved three stages, with the first stage being the localized oil-displacing-water mode, the second being the large-scale oil-displacing-water mode, and the third being the late progressive gas-displacing-oil mode.
Series Solution Method for Solving Sequential Caputo Fractional Differential Equations
Authors: Vatsala Aghalaya S. , Pageni Govinda
Published: October 2023

Computing the solution of the Caputo fractional differential equation plays an important role in using the order of the fractional derivative as a parameter to enhance the model. In this work, we developed a power series solution method to solve a linear Caputo fractional differential equation of the order q,0<q<1, and this solution matches with the integer solution for q=1. In addition, we also developed a series solution method for a linear sequential Caputo fractional differential equation with constant coefficients of order 2q, which is sequential for order q with Caputo fractional initial conditions. The advantage of our method is that the fractional order q can be used as a parameter to enhance the mathematical model, compared with the integer model. The methods developed here, namely, the series solution method for solving Caputo fractional differential equations of constant coefficients, can be extended to Caputo sequential differential equation with variable coefficients, such as fractional Bessel’s equation with fractional initial conditions.
AI-Enabled Electrocardiogram Analysis for Disease Diagnosis
Authors: Khan Mamun Mohammad Mahbubur Rahman , Elfouly Tarek
Published: October 2023

Contemporary methods used to interpret the electrocardiogram (ECG) signal for diagnosis or monitoring are based on expert knowledge and rule-centered algorithms. In recent years, with the advancement of artificial intelligence, more and more researchers are using deep learning (ML) and deep learning (DL) with ECG data to detect different types of cardiac issues as well as other health problems such as respiration rate, sleep apnea, and blood pressure, etc. This study presents an extensive literature review based on research performed in the last few years where ML and DL have been applied with ECG data for many diagnoses. However, the review found that, in published work, the results showed promise. However, some significant limitations kept that technique from implementation in reality and being used for medical decisions; examples of such limitations are imbalanced and the absence of standardized dataset for evaluation, lack of interpretability of the model, inconsistency of performance while using a new dataset, security, and privacy of health data and lack of collaboration with physicians, etc. AI using ECG data accompanied by modern wearable biosensor technologies has the potential to allow for health monitoring and early diagnosis within reach of larger populations. However, researchers should focus on resolving the limitations.
Exponential Stability and Relative Controllability of Nonsingular Conformable Delay Systems
Authors: Zhou Airen
Published: October 2023

In this paper, we investigate a delayed matrix exponential and utilize it to derive a representation of solutions to a linear nonsingular delay problem with permutable matrices. To begin with, we present a novel definition of α-exponential stability for these systems. Subsequently, we put forward several adequate conditions to ensure the α-exponential stability of solutions for such delay systems. Moreover, by constructing a Grammian matrix that accounts for delays, we provide a criterion to determine the relative controllability of a linear problem. Additionally, we extend our analysis to nonlinear problems. Lastly, we offer several examples to verify the effectiveness of our theoretical findings.
Synthetic Battery Data Generation and Validation for Capacity Estimation
Authors: Pyne Moinak , Yurkovich Benjamin J. , Yurkovich Stephen
Published: October 2023

Simple parameter-based models are typically unable to function in all situations due to the rapidly tightening margins for error in the use of contemporary estimation techniques. The development of data-driven models as a result has made the availability of trustworthy battery data essential. The generation of such data from battery systems necessitates prolonged cycling tests that can last for months, which makes data collection challenging. In this article, a combination of approaches is presented that uses measured operational data from battery packs to generate synthetic data utilizing Markov chains and neural networks in order to ultimately estimate the capacity fade based on operational drive cycle data. The experimental data used for this study are generated using scaled operational cycles with multiple charge/discharge pulses applied repetitively on a commercially available battery pack. The synthetically generated data have the flexibility of matching user-imposed conditions, and have potential for a variety of applications in the analysis and safety of commercial battery systems. Finally, capacity estimation results present the outcome of a comprehensive study into capacity fade estimation in battery packs.
The Paracrine Effect of Hyaluronic Acid-Treated Endothelial Cells Promotes BMP-2-Mediated Osteogenesis
Authors: Tong Xiaojie , Chen Jin , Wang Renqin , Hou Dan , Wu Gang , Liu Chang , Pathak Janak Lal
Published: October 2023

The combination of hyaluronic acid (HA) and BMP-2 has been reported to promote bone regeneration. However, the interaction of endothelial cells and bone marrow mesenchymal stem cells (BMSCs) during HA + BMP-2 treatment is not fully understood. This study aimed to analyze the direct effect of HA, as well as the paracrine effect of HA-treated endothelial cells, on the BMP-2-mediated osteogenic differentiation of BMSCs. The angiogenic differentiation potential of HA at different molecular weights and different concentrations was tested. The direct effect of HA, as well as the indirect effect of HA-treated human umbilical cord endothelial cells (HUVECs, i.e., conditioned medium (CM)-based co-culture) on the BMP-2-mediated osteogenic differentiation of BMSCs was analyzed using alkaline phosphatase (ALP) staining and activity, alizarin red S (ARS) staining, and RT-qPCR of osteogenic markers. Angiogenic differentiation markers were also analyzed in HUVECs after treatment with HA + BMP-2. The bone regeneration potential of BMP-2 and HA + BMP-2 was analyzed in a rat ectopic model. We found that 1600 kDa HA at 300 µg/mL promoted tube formation by HUVECs in vitro and upregulated the mRNA expression of the angiogenic markers CD31, VEGF, and bFGF. HA inhibited, but conditioned medium from HA-treated HUVECs promoted, the BMP-2-mediated osteogenic differentiation of BMSCs, as indicated by the results of ALP staining and activity, ARS staining, and the mRNA expression of the osteogenic markers RUNX-2, ALP, COLI, and OPN. HA + BMP-2 (50 ng/mL) upregulated the expression of the angiogenesis-related genes VEGF and bFGF in HUVECs and bone regeneration in vivo compared to BMP-2 treatment. In conclusion, the paracrine effect of hyaluronic acid-treated endothelial cells promotes BMP-2-mediated osteogenesis, suggesting the application potential of HA + BMP-2 in bone tissue engineering.
Immunotherapy in Acute Myeloid Leukemia: A Literature Review of Emerging Strategies
Authors: Guarnera Luca , Bravo-Perez Carlos , Visconte Valeria
Published: October 2023

In the last twenty years, we have witnessed a paradigm shift in the treatment and prognosis of acute myeloid leukemia (AML), thanks to the introduction of new efficient drugs or approaches to refine old therapies, such as Gemtuzumab Ozogamicin, CPX 3-5-1, hypomethylating agents, and Venetoclax, the optimization of conditioning regimens in allogeneic hematopoietic stem cell transplantation and the improvement of supportive care. However, the long-term survival of non-M3 and non-core binding factor-AML is still dismal. For this reason, the expectations for the recently developed immunotherapies, such as antibody-based therapy, checkpoint inhibitors, and chimeric antigen receptor strategies, successfully tested in other hematologic malignancies, were very high. The inherent characteristics of AML blasts hampered the development of these treatments, and the path of immunotherapy in AML has been bumpy. Herein, we provide a detailed review of potential antigenic targets, available data from pre-clinical and clinical trials, and future directions of immunotherapies in AML.
Genes and Pathway Reactions Related to Carotenoid Biosynthesis in Purple Bacteria
Authors: Sandmann Gerhard
Published: October 2023

In purple bacteria, the genes of the carotenoid pathways are part of photosynthesis gene clusters which were distributed among different species by horizontal gene transfer. Their close organisation facilitated the first-time cloning of carotenogenic genes and promoted the molecular investigation of spheroidene and spirilloxanthin biosynthesis. This review highlights the cloning of the spheroidene and spirilloxanthin pathway genes and presents the current knowledge on the enzymes involved in the carotenoid biosynthesis of purple sulphur and non-sulphur bacteria. Mostly, spheroidene or spirilloxanthin biosynthesis exists in purple non-sulphur bacteria but both pathways operate simultaneously in Rubrivivax gelatinosus. In the following years, genes from other bacteria including purple sulphur bacteria with an okenone pathway were cloned. The individual steps were investigated by kinetic studies with heterologously expressed pathway genes which supported the establishment of the reaction mechanisms. In particular, the substrate and product specificities revealed the sequential order of the speroidene and spiriloxanthin pathways as well as their interactions. Information on the enzymes involved revealed that the phytoene desaturase determines the type of pathway by the formation of different products. By selection of mutants with amino acid exchanges in the putative substrate-binding site, the neurosporene-forming phytoene desaturase could be changed into a lycopene-producing enzyme and vice versa. Concerning the oxygen groups in neurosporene and lycopene, the tertiary alcohol group at C1 is formed from water and not by oxygenation, and the C2 or C4 keto groups are inserted differently by an oxygen-dependent or oxygen-independent ketolation reaction, respectively.
Minimal Residual Disease Detected by the 7NB-mRNAs ddPCR Assay Is Associated with Disease Progression in High-Risk Neuroblastoma Patients: A Prospective Multicenter Observational Study in Japan
Authors: Nishimura Noriyuki , Ishida Toshiaki , Yokota Isao , Matsumoto Kimikazu , Shichino Hiroyuki , Fujisaki Hiroyuki , Sarashina Takeo , Kamijo Takehiko , Takimoto Tetsuya , Iehara Tomoko , Tajiri Tatsuro ,   on behalf of the JCCG Neuroblastoma Committee
Published: October 2023

High-risk neuroblastoma (HR-NB) patients remain far from obtaining optimal outcomes, with more than 50% relapse/regrowth rate despite current intensive multimodal therapy. This originated from the activation/proliferation of chemoresistant minimal residual disease (MRD). MRD with a significant prognostic was reported by several quantitative PCR (qPCR) or droplet digital PCR (ddPCR) assays quantitating different sets of NB-associated mRNAs (NB-mRNAs). The 7NB-mRNAs ddPCR assay quantitating CRMP1, DBH, DDC, GAP43, ISL1, PHOX2B, and TH mRNAs was reported to outperform other qPCR assays by a retrospective in-house observational study. In the present study, the Japan Children’s Cancer Group (JCCG) Neuroblastoma Committee conducted a prospective multicenter observational study aimed at evaluating a prognostic value of MRD in bone marrow (BM-MRD) and peripheral blood (PB-MRD) detected by 7NB-mRNAs ddPCR assay. Between August 2018 and August 2022, 7 HR-NB patients who registered for JCCG clinical trials (JN-H-11 and JN-H-15) were enrolled. A total of 19 BM and 19 PB samples were collected, and 4/15 BM and 4/15 PB samples were classified as progressive disease (PD)/non-PD samples. BM-MRD and PB-MRD estimated area under curve (AUC) of 0.767 and 0.800 with a significant accuracy (AUC > 0.7). The present study validated a prognostic value of BM-MRD obtained by a previous study (AUC 0.723) and revealed the significant accuracy of PB-MRD as well as BM-MRD.
Implications for Combination Therapy of Selective Monoamine Reuptake Inhibitors on Dopamine Transporters
Authors: Ahn Hyomin , Park Kichul , Kim Dongyoung , Chi Sung-Gil , Choi Kee-Hyun , Han Seo-Jung , Song Chiman
Published: October 2023

Monoamine transporters, including dopamine, norepinephrine, and serotonin transporters (DAT, NET, and SERT, respectively), are important therapeutic targets due to their essential roles in the brain. To overcome the slow action of selective monoamine reuptake inhibitors, dual- or triple-acting inhibitors have been developed. Here, to examine whether combination treatments of selective reuptake inhibitors have synergistic effects, the pharmacological properties of DAT, NET, and SERT were investigated using the selective inhibitors of each transporter, which are vanoxerine, nisoxetine, and fluoxetine, respectively. Potencies were determined via fluorescence-based substrate uptake assays in the absence and presence of other inhibitors to test the multi-drug effects on individual transporters, resulting in antagonistic effects on DAT. In detail, fluoxetine resulted in a 1.6-fold increased IC50 value of vanoxerine for DAT, and nisoxetine produced a more drastic increase in the IC50 value by six folds. Furthermore, the effects of different inhibitors, specifically monovalent ions, were tested on DAT inhibition by vanoxerine. Interestingly, these ions also reduced vanoxerine potency in a similar manner. The homology models of DAT suggested a potential secondary inhibitor binding site that affects inhibition in an allosteric manner. These findings imply that the use of combination therapy with monoamine reuptake inhibitors should be approached cautiously, as antagonistic effects may occur.
Diagnostic Value of Dynamic Magnetic Resonance Imaging (dMRI) of the Pelvic Floor in Genital Prolapses
Authors: Gilyadova Aida , Ishchenko Anton , Puchkova Elena , Mershina Elena , Petrovichev Viktor , Reshetov Igor
Published: October 2023

Pelvic organ prolapse is a chronic disease resulting from a weakening of the musculoskeletal apparatus of the pelvic organs. For the diagnosis of this pathology, it is insufficient to conduct only a clinical examination. An effective diagnostic tool is the method of dynamic magnetic resonance imaging (MRI) of the pelvic floor, which allows a comprehensive assessment of the anatomical and functional characteristics of the walls of the pelvis and pelvic organs. The aim of the study was to analyze the literature data on the possibilities and limitations of using dynamic MRI in pelvic organ prolapse. The widespread use of the dynamic MRI method is due to the high quality of the resulting image, good reproducibility, and the maximum ability to display the characteristics of the pelvic floor. Dynamic MRI of the small pelvis allows a comprehensive assessment of the anatomical and functional features of the pelvis, excluding the effect of ionizing radiation on the body. The method is characterized by good visualization with high resolution and excellent soft tissue contrast. The method allows for assessing the state of the evacuation function of visualized structures in dynamics. Simultaneous imaging of all three parts of the pelvic floor using dynamic MRI makes it possible to assess multicompartment disorders. The anatomical characteristics of the state of the pelvic organs in the norm and in the event of prolapse are considered. The technique for performing the method and the procedure for analyzing the resulting images are described. The possibilities of diagnosing a multicomponent lesion are considered, while it is noted that dynamic MRI of the pelvic organs provides visualization and functional analysis of all three parts of the pelvis and often allows the choice and correction of tactics for the surgical treatment of pelvic organ prolapse. It is noted that dynamic MRI is characterized by a high resolution of the obtained images, and the advantage of the method is the ability to detect functional changes accompanying the pathology of the pelvic floor.
Detecting Microsatellite Instability in Endometrial, Colon, and Stomach Cancers Using Targeted NGS
Authors: Boyarskikh Ulyana , Kechin Andrey , Khrapov Evgeniy , Fedyanin Mikhail , Raskin Grigory , Mukhina Marina , Kravtsova Elena , Tsukanov Aleksey , Achkasov Sergey , Filipenko Maksim
Published: October 2023

Purpose: To develop a method for testing the MSI based on targeted NGS. Methods: Based on the results of previous studies, 81 microsatellite loci with high variability in MSI-H tumors were selected, and a method for calculating the MSI score was developed. Using the MSI score, we defined the MSI status in endometral (162), colon (153), and stomach (190) cancers. Accuracy of the MSI scores was evaluated by comparison with MMR immunohistochemistry for 137 endometrium (63 dMMR and 74 pMMR), 76 colon (29 dMMR and 47 pMMR), and 81 stomach (8 dMMR and 73 pMMR) cancers. Results: Classification of MSS and MSI-H tumors was performed with AUC (0.99), sensitivity (92%), and specificity (98%) for all tumors without division into types. The accuracy of MSI testing in endometrial cancer was lower than for stomach and colon cancer (0.98, 87%, and 100%, respectively). The use of 27 loci only, the most informative for endometrial cancer, increased the overall accuracy (1.00, 99%, and 99%). Comparison of MSI score values in 505 tumors showed that MSI score is significantly higher in colon (p < 10−5) and stomach (p = 0.008) cancer compared with endometrial cancer. Conclusion: The MSI score accurately determines MSI status for endometrial, colon, and stomach cancers and can be used to quantify the degree of MSI.
The Role of Carbon Ion Therapy in the Changing Oncology Landscape—A Narrative Review of the Literature and the Decade of Carbon Ion Experience at the Italian National Center for Oncological Hadrontherapy
Authors: Orlandi Ester , Barcellini Amelia , Vischioni Barbara , Fiore Maria Rosaria , Vitolo Viviana , Iannalfi Alberto , Bonora Maria , Chalaszczyk Agnieszka , Ingargiola Rossana , Riva Giulia , Ronchi Sara , Valvo Francesca , Fossati Piero , Ciocca Mario , Mirandola Alfredo , Molinelli Silvia , Pella Andrea , Baroni Guido , Pullia Marco Giuseppe , Facoetti Angelica , Orecchia Roberto , Licitra Lisa , Vago Gianluca , Rossi Sandro
Published: October 2023

Background: Currently, 13 Asian and European facilities deliver carbon ion radiotherapy (CIRT) for preclinical and clinical activity, and, to date, 55 clinical studies including CIRT for adult and paediatric solid neoplasms have been registered. The National Center for Oncological Hadrontherapy (CNAO) is the only Italian facility able to accelerate both protons and carbon ions for oncological treatment and research. Methods: To summarise and critically evaluate state-of-the-art knowledge on the application of carbon ion radiotherapy in oncological settings, the authors conducted a literature search till December 2022 in the following electronic databases: PubMed, Web of Science, MEDLINE, Google Scholar, and Cochrane. The results of 68 studies are reported using a narrative approach, highlighting CNAO’s clinical activity over the last 10 years of CIRT. Results: The ballistic and radiobiological hallmarks of CIRT make it an effective option in several rare, radioresistant, and difficult-to-treat tumours. CNAO has made a significant contribution to the advancement of knowledge on CIRT delivery in selected tumour types. Conclusions: After an initial ramp-up period, CNAO has progressively honed its clinical, technical, and dosimetric skills. Growing engagement with national and international networks and research groups for complex cancers has led to increasingly targeted patient selection for CIRT and lowered barriers to facility access.
Image-Based Modeling of Drug Delivery during Intraperitoneal Chemotherapy in a Heterogeneous Tumor Nodule
Authors: Rezaeian Mohsen , Heidari Hamidreza , Raahemifar Kaamran , Soltani Madjid
Published: October 2023

Intraperitoneal (IP) chemotherapy is a promising treatment approach for patients diagnosed with peritoneal carcinomatosis, allowing the direct delivery of therapeutic agents to the tumor site within the abdominal cavity. Nevertheless, limited drug penetration into the tumor remains a primary drawback of this method. The process of delivering drugs to the tumor entails numerous complications, primarily stemming from the specific pathophysiology of the tumor. Investigating drug delivery during IP chemotherapy and studying the parameters affecting it are challenging due to the limitations of experimental studies. In contrast, mathematical modeling, with its capabilities such as enabling single-parameter studies, and cost and time efficiency, emerges as a potent tool for this purpose. In this study, we developed a numerical model to investigate IP chemotherapy by incorporating an actual image of a tumor with heterogeneous vasculature. The tumor’s geometry is reconstructed using image processing techniques. The model also incorporates drug binding and uptake by cancer cells. After 60 min of IP treatment with Doxorubicin, the area under the curve (AUC) of the average free drug concentration versus time curve, serving as an indicator of drug availability to the tumor, reached 295.18 mol·m−3·s−1. Additionally, the half-width parameter W1/2, which reflects drug penetration into the tumor, ranged from 0.11 to 0.14 mm. Furthermore, the treatment resulted in a fraction of killed cells reaching 20.4% by the end of the procedure. Analyzing the spatial distribution of interstitial fluid velocity, pressure, and drug concentration in the tumor revealed that the heterogeneous distribution of tumor vasculature influences the drug delivery process. Our findings underscore the significance of considering the specific vascular network of a tumor when modeling intraperitoneal chemotherapy. The proposed methodology holds promise for application in patient-specific studies.
Determining the Effectiveness of Fibrin Sealants in Reducing Complications in Patients Undergoing Lateral Neck Dissection (DEFeND): A Randomised External Pilot Trial
Authors: Bajwa Mandeep S. , Jackson Richard , Dhanda Jagtar , Tudur Smith Catrin , Shaw Richard J. , Schache Andrew G.
Published: October 2023

Objectives: High-quality randomised controlled trials (RCT) to support the use of Fibrin Sealants (FS) in neck dissection (ND) are lacking. The DEFeND trial assessed critical pilot/feasibility questions and signals from clinical outcomes to inform a future definitive trial. Patients and Methods: The study design piloted was a blinded surgical RCT. All participants underwent unilateral ND for head and neck cancer. Interventional arm: ND with application of FS. Control arm: ND alone. Feasibility outcomes included recruitment, effectiveness of blinding, protocol adherence and evaluating administrative processes. Clinical outcomes included surgical complications (primary outcome), drainage volume, time to drain removal, length of hospital stay, pain and the Neck Dissection Impairment Index. Results: Recruitment completed ahead of time. Fifty-three patients were recruited, and 48 were randomised at a rate of 5.3 patients/month. Blinding of patients, research nurses and outcome assessors was effective. Two protocol deviations occurred. Two patients were lost to follow-up. The mean (SD) Comprehensive Complication Index in the interventional arm was 6.5 (12.8), and it was 9.9 (14.2) in the control arm. The median (IQR) time to drain removal (days) was shorter in the interventional arm (2.67 (2.42, 3.58) vs. 3.40 (2.50, 4.27)). However, this did not translate to a clinically significant reduction in median (IQR) length of hospital stay in days (intervention: 3.48 (2.64, 4.54), control: 3.74 (3.11, 4.62)). Conclusion: The proposed trial design was effective, and a definitive surgical trial is feasible. Whilst there was a tendency for FS to improve clinical outcomes, the effect size did not reach clinical or statistical significance. (ISRCTN99181100).
A Humanized and Defucosylated Antibody against Podoplanin (humLpMab-23-f) Exerts Antitumor Activities in Human Lung Cancer and Glioblastoma Xenograft Models
Authors: Suzuki Hiroyuki , Ohishi Tomokazu , Kaneko Mika K. , Kato Yukinari
Published: October 2023

A cancer-specific anti-PDPN mAb, LpMab-23 (mouse IgG1, kappa), was established in our previous study. We herein produced a humanized IgG1 version (humLpMab-23) and defucosylated form (humLpMab-23-f) of an anti-PDPN mAb to increase ADCC activity. humLpMab-23 recognized PDPN-overexpressed Chinese hamster ovary (CHO)-K1 (CHO/PDPN), PDPN-positive PC-10 (human lung squamous cell carcinoma), and LN319 (human glioblastoma) cells via flow cytometry. We then demonstrated that humLpMab-23-f induced ADCC and complement-dependent cytotoxicity against CHO/PDPN, PC-10, and LN319 cells in vitro and exerted high antitumor activity in mouse xenograft models, indicating that humLpMab-23-f could be useful as an antibody therapy against PDPN-positive lung squamous cell carcinomas and glioblastomas.
Immunogenic Biomarkers HMGB1 and sRAGE Are Potential Diagnostic Tools for Ovarian Malignancies
Authors: Schröder Lars , Rupp Alexander B. A. , Gihr Kathrin M. E. , Kobilay Makbule , Domroese Christian M. , Mallmann Michael R. , Holdenrieder Stefan
Published: October 2023

Background: High mobility group box 1 (HMGB1), soluble receptor of advanced glycation end products (sRAGE) and programmed cell death markers PD-1 and PD-L1 are immunogenic serum biomarkers that may serve as novel diagnostic tools for cancer diagnosis. Methods: We investigated the four markers in sera of 231 women, among them 76 with ovarian cancer, 87 with benign diseases and 68 healthy controls, using enzyme immunoassays. Discrimination between groups was calculated using receiver operating characteristic (ROC) curves and sensitivities at fixed 90% and 95% specificities. Results: HMGB1 levels were significantly elevated and sRAGE levels were decreased in cancer patients as compared to benign and healthy controls. In consequence, the ratio of HMGB1 and sRAGE discriminated best between diagnostic groups. The areas under the curve (AUCs) of the ROC curves for differentiation of cancer vs. healthy were 0.77 for HMGB1, 0.65 for sRAGE and 0.78 for the HMGB1/sRAGE ratio, and slightly lower for the differentiation of cancer vs. benigns with 0.72 for HMGB1, 0.61 for sRAGE and 0.74 for the ratio of both. The highest sensitivities for cancer detection at 90% specificity versus benign diseases were achieved using HMGB1 with 41.3% and the HMGB1/sRAGE ratio with 39.2%, followed by sRAGE with 18.9%. PD-1 showed only minor and PD-L1 no power for discrimination between ovarian cancer and benign diseases. Conclusion: HMGB1 and sRAGE have differential diagnostic potential for ovarian cancer detection and warrant inclusion in further validation studies.
Therapeutic Results and Survival of Patients with Myelofibrosis Treated with Ruxolitinib—A Real-Life Longitudinal Study
Authors: Stoeva Vera , Mihaylov Georgi , Mitov Konstantin , Petrova Guenka , Tachkov Konstantin
Published: October 2023

The aim of this study was to analyze the therapeutic results and survival of patients with myelofibrosis treated with ruxolitinib in comparison with a group on standard therapy. It is a cross-sectional, retrospective, non-interventional, real-life study that was performed between January 2000 and February 2023. Patients treated between 2000 and 2016, before the introduction of ruxolitinib, constituted the control group (n = 45), while those treated after May 2016, after ruxolitinib inclusion, constituted the active group (n = 66). Demographic characteristics, clinical indicators, the severity of the disease, and survival were explored using Kaplan–Meier survival analyses. Spearman’s correlation, linear regression, and other statistical analyses were performed. According to the Kaplan–Meier analysis, there was a 75.33% reduction in the fatality risk in the sample. On a general-population level, the fatality risk in the group treated with ruxolitinib varied between 7.9% and 77.18% compared to that of the risk in the control group. There was a decrease in blood parameters (leukocytes, hemoglobin, and platelets) and spleen size. During the first six months, the spleen size of the patients on ruxolitinib decreased by 6%, and during the second six months, it decreased by another 9%. This study shows that patients in a real-life clinical setting treated with ruxolitinib exhibited improved clinical signs of the disease, had a lower symptom severity, and survived longer than patients on standard therapy before ruxolitinib’s entrance into the national market. The improvements correlate with those reported in randomized clinical trials.
N-Terminal Processing and Modification of Ciliary Dyneins
Authors: Sakato-Antoku Miho , Balsbaugh Jeremy L. , King Stephen M.
Published: October 2023

Axonemal dyneins are highly complex microtubule motors that power ciliary motility. These multi-subunit enzymes are assembled at dedicated sites within the cytoplasm. At least nineteen cytosolic factors are specifically needed to generate dynein holoenzymes and/or for their trafficking to the growing cilium. Many proteins are subject to N-terminal processing and acetylation, which can generate degrons subject to the AcN-end rule, alter N-terminal electrostatics, generate new binding interfaces, and affect subunit stoichiometry through targeted degradation. Here, we have used mass spectrometry of cilia samples and electrophoretically purified dynein heavy chains from Chlamydomonas to define their N-terminal processing; we also detail the N-terminal acetylase complexes present in this organism. We identify four classes of dynein heavy chain based on their processing pathways by two distinct acetylases, one of which is dependent on methionine aminopeptidase activity. In addition, we find that one component of both the outer dynein arm intermediate/light chain subcomplex and the docking complex is processed to yield an unmodified Pro residue, which may provide a setpoint to direct the cytosolic stoichiometry of other dynein complex subunits that contain N-terminal degrons. Thus, we identify and describe an additional level of processing and complexity in the pathways leading to axonemal dynein formation in cytoplasm.
Improving Efficiency of Direct Pro-Neural Reprogramming: Much-Needed Aid for Neuroregeneration in Spinal Cord Injury
Authors: Chudakova Daria A. , Samoilova Ekaterina M. , Chekhonin Vladimir P. , Baklaushev Vladimir P.
Published: October 2023

Spinal cord injury (SCI) is a medical condition affecting ~2.5–4 million people worldwide. The conventional therapy for SCI fails to restore the lost spinal cord functions; thus, novel therapies are needed. Recent breakthroughs in stem cell biology and cell reprogramming revolutionized the field. Of them, the use of neural progenitor cells (NPCs) directly reprogrammed from non-neuronal somatic cells without transitioning through a pluripotent state is a particularly attractive strategy. This allows to “scale up” NPCs in vitro and, via their transplantation to the lesion area, partially compensate for the limited regenerative plasticity of the adult spinal cord in humans. As recently demonstrated in non-human primates, implanted NPCs contribute to the functional improvement of the spinal cord after injury, and works in other animal models of SCI also confirm their therapeutic value. However, direct reprogramming still remains a challenge in many aspects; one of them is low efficiency, which prevents it from finding its place in clinics yet. In this review, we describe new insights that recent works brought to the field, such as novel targets (mitochondria, nucleoli, G-quadruplexes, and others), tools, and approaches (mechanotransduction and electrical stimulation) for direct pro-neural reprogramming, including potential ones yet to be tested.
ZnO for Photoelectrochemical Hydrogen Generation
Authors: Bakranova Dina , Nagel David
Published: October 2023

The rise in the Earth’s surface temperature on an annual basis has stimulated scientific and engineering interest in developing and implementing alternative energy sources. Besides cost, the main requirements for alternative energy sources are renewability and environmental friendliness. A prominent representative that allows the production of “green” energy is the conversion of solar photons into a practical energy source. Among the existing approaches in solar energy conversion, the process of photoelectrochemical (PEC) hydrogen extraction from water, which mimics natural photosynthesis, is promising. However, direct decomposition of water by sunlight is practically impossible since water is transparent to light waves longer than 190 nm. Therefore, applying a photoelectrochemical process using semiconductor materials and organic compounds is necessary. Semiconductor materials possessing appropriately positioned valence and conduction bands are vital constituents of photoelectrodes. Certain materials exhibit semiconductor characteristics that facilitate the reduction-oxidation (RedOx) reaction of water (H2O) under specific circumstances. ZnO holds a unique position in the field of photocatalysis due to its outstanding characteristics, including remarkable electron mobility, high thermal conductivity, transparency, and more. This article offers an overview of studies exploring ZnO’s role as a photocatalyst in the generation of hydrogen from water.
Genomic Profiling and Molecular Characterization of Clear Cell Renal Cell Carcinoma
Authors: Pezzicoli Gaetano , Ciciriello Federica , Musci Vittoria , Salonne Francesco , Ragno Anna , Rizzo Mimma
Published: October 2023

Clear cell renal cell carcinoma (ccRCC) treatment has undergone three major paradigm shifts in recent years, first with the introduction of molecular targeted therapies, then with immune checkpoint inhibitors, and, more recently, with immune-based combinations. However, to date, molecular predictors of response to targeted agents have not been identified for ccRCC. The WHO 2022 classification of renal neoplasms introduced the molecularly defined RCC class, which is a first step in the direction of a better molecular profiling of RCC. We reviewed the literature data on known genomic alterations of clinical interest in ccRCC, discussing their prognostic and predictive role. In particular, we explored the role of VHL, mTOR, chromatin modulators, DNA repair genes, cyclin-dependent kinases, and tumor mutation burden. RCC is a tumor whose pivotal genomic alterations have pleiotropic effects, and the interplay of these effects determines the tumor phenotype and its clinical behavior. Therefore, it is difficult to find a single genomic predictive factor, but it is more likely to identify a signature of gene alterations that could impact prognosis and response to specific treatment. To accomplish this task, the interpolation of large amounts of clinical and genomic data is needed. Nevertheless, genomic profiling has the potential to change real-world clinical practice settings.
Exploring the Relationship between Self-Rated Health and Unmet Cancer Needs among Sexual and Gender Minority Adolescents and Young Adults with Cancer
Authors: Francis-Levin Nina , Ghazal Lauren V. , Francis-Levin Jess , Zebrack Bradley , Chen Meiyan , Zhang Anao
Published: October 2023

This study evaluates the unmet needs of sexual and gender minority (SGM) adolescent and young adult (AYA) cancer survivors by comparing SGM AYA self-rated health (SRH) scores to their non-SGM (i.e., cisgender/heterosexual) counterparts. The Cancer Needs Questionnaire—Young People (CNQ-YP) and self-rated health measures were used to assess unmet needs in AYAs aged 15–39 who had been diagnosed with cancer in the previous ten years (n = 342). Participants were recruited from a National Cancer Institute (NCI) Comprehensive Cancer Center registry using the modified Dillman’s method. Self-reported sexual orientation and gender identity (SO/GI) data were collected. Independent t-tests were used to test between-group differences in unmet needs and Pearson’s chi-square test was used to determine the difference in SRH scores between SGM and non-SGM AYA cancer survivors. SGM AYA cancer survivors reported greater mean needs than their non-SGM counterparts across all six domains and reported significantly greater needs in the domains of Feelings and Relationships, t(314) = −2.111, p = 0.036, Information and Activities, t(314) = −2.594, p = 0.009, and Education, t(207) = −3.289, p < 0.001. SGM versus non-SGM SRH scores were significantly different, indicating that a higher percentage of SGM AYAs reported poor/fair health compared to those who were non-SGM. Unmet life and activities needs were negatively associated with AYA cancer survivors’ SRH, whereas unmet work needs were positively associated with AYA cancer survivors’ SRH. An AYA’s gender identity (SGM versus non-SGM) was not a moderator. SGM AYAs are an understudied group within an already vulnerable patient population. Unmet psychosocial needs related to one’s feelings and relationships, and information and activity needs merit further research to develop tailored interventions that reflect the experiences of SGM AYAs.
Local Treatment Efficacy for Single-Area Squamous Cell Carcinoma of the Unknown Primary Site
Authors: Kurita Tomoko , Yunokawa Mayu , Tanaka Yuji , Okamoto Kota , Kanno Motoko , Fusegi Atsushi , Omi Makiko , Netsu Sachiho , Nomura Hidetaka , Tonooka Akiko , Kanao Hiroyuki
Published: October 2023

The prognosis for cancer of unknown primary site (CUP) is poor, and squamous cell carcinoma of the unknown primary site (SCCUP) is a rare histological type. CUP is often treated with aggressive multimodal treatments, while the treatment of single-area localized CUP remains controversial. We retrospectively reviewed the medical records of patients with CUP. SCCUP in women was classified according to several definitions. Based on the histologic type and site, they were classified into favorable and unfavorable subsets. We further divided SCCUP into two types (single and multiple areas) and reviewed treatment and efficacy. Among the 227 female CUP patients, 36 (15%) had SCCUP. The median age was 59.9 years (range, 31–90 years). Most patients (61.1%) had a good performance status. Of the SCCUP patients, 22 had cancer in a single area, and 14 in multiple areas. Single-area SCCUP was further divided into favorable (16 cases) and unfavorable subsets (6 cases). In the favorable subset, local treatment was predominant, and almost all cases had a good prognosis. Even in the unfavorable subset, local therapy was combined with systemic chemotherapy in only two cases, and four cases showed no recurrences. Local treatment may be effective for single-area SCCUP, even in the unfavorable subset.
Taxonomy and Phylogeny of Endophytic Fungi (Chaetomiaceae) Associated with Healthy Leaves of Mangifera indica in Yunnan, China
Authors: Yang Er-Fu , Karunarathna Samantha C. , Dai Dong-Qin , Priyashantha Alviti Kankanamalage Hasith , Promputtha Itthayakorn , Elgorban Abdallah , Tibpromma Saowaluck
Published: October 2023

Mangoes belong to Mangifera (Anacardiaceae), which contains 69 species, but only Mangifera indica is popularly cultivated and commercialized. Mango is one of the most important crops grown in China’s Yunnan Province and significantly contributes to the economic security of these locals. Endophytic fungi have been recognized as beneficial microbes that improve plant growth, productivity, and survivability under environmental stress. Nevertheless, many host plant-related endophytic fungi are yet to be identified, including the mango-related species. During this study, we recognized three different fungal species in the family Chaetomiaceae derived from healthy mango (Mangifera indica) leaves based on morphological examinations coupled with multi-gene phylogenetic analysis (ITS, LSU, rpb2, and tub2). These species are Dichotomopilus funicola (KUNCC23-13347) and Humicola wallefii (KUNCC22-10759, 23-13348), derived from new hosts, and a new species of Arcopilus hongheensis (KUNCC22-10767, 23-13346).
‘Something Better than a Cure’ in Times of Mental Health Crisis
Authors: Williams Emma
Published: October 2023

In this paper, I turn to Adam Phillips’ recent discussion of the vexed nature of cure in psychoanalysis to consider the structural differences between mental and physical health. I examine how psychoanalytic thinking raises questions for naturalistic ways of thinking about mental health and for broader crisis narratives that are becoming prevalent in Western modernity. In the latter half of this paper, I draw a comparison between thinking about matters of health and ways of thinking in the philosophy of education. I suggest that the lure of cure can be detected in statements of universalist aims and ends for education (which themselves have come to invoke conceptions of wellbeing and mental health in modern times). I also explore Phillps’ account of psychoanalysis as ‘something better than a cure’ and consider its implications for future thinking in the philosophy of education.
REM-Based Indoor Localization with an Extra-Trees Regressor
Authors: Aziz Toufiq , Camana Mario R. , Garcia Carla E. , Hwang Taewoong , Koo Insoo
Published: October 2023

As a widely established and accessible infrastructure, wireless local area networks (WLANs) have emerged as a viable option for indoor localization for both mobile and stationary users. However, WLANs present several challenges that must be fulfilled to achieve localization based on Wi-Fi signals and to obtain proper coverage prediction maps. This paper presents a study based on the application of extra-trees regression (ETR) for indoor localization using coverage prediction maps. The aim of the proposed method is to accurately estimate a user’s position within a radio environment map (REM) area using collected signal strength indicator (RSSI) values collected by a mobile robot. Our methodology consists of utilizing the RSSI collected values to construct the REM, which is then leveraged to create a dataset for indoor localization. This process involves tracking a user’s movements within a specific area of interest while considering a single access point. The proposed scheme explores various machine learning (ML) regression algorithms, with hyperparameter tuning carried out to optimize their performance through 10-fold cross-validation. To assess the REM, we employed metrics, such as the root mean square error, absolute error, and R-squared error. Additionally, we evaluated the indoor localization accuracy using location error metrics. Among the ML techniques assessed, our proposed ETR-based approach demonstrates the highest performance based on these error metrics. The combination of generating coverage maps and utilizing regression techniques for localization presents a potent approach for analyzing the radio frequency environment in indoor spaces.