bluuebunny/crossref_metadata_2025 huggingface dataset:
Islamic Economics: Wage Maximization
Authors: Baaquie Belal Ehsan
Published: December 2024

It is proposed that wage maximization is one of the fundamental principles of Islamic economics, and should be counter-posed to the profit maximization principle of capitalism. Wage maximization needs to be analyzed for both the macroeconomy as well as for the microeconomy, since wage maximization has to be realized at the level of the firms of the microeconomy. A mathematical model for the Islamic macroeconomy is postulated that determines how to maximize macroeconomic wages. A model for a firm is proposed that pays minimum wages based on macroeconomic wage maximization. Wages can be further augmented by wages having a variable component based on profit and loss sharing by the workers with the firm, and which entails a degree of risk. Fixing the variable wage component results in the rate of profit of all firms becoming equal to the macroeconomic wage maximizing macroeconomic rate of profit.
Mechanism of Action of PARP Inhibitors
Authors: Kim Chiho , Yu Yonghao
Published: December 2024

The selective vulnerability of BRCA1/2-mutated (BRCA
mut) cancer cells to poly(ADP-ribose) polymerase (PARP) inhibitors provides one of the best examples of synthetic lethality that has been translated into the clinic. The success of this approach has led to a paradigm shift, with four PARP inhibitors now approved by the US Food and Drug Administration (FDA) for the treatment of ovarian, breast, prostate, and/or pancreatic cancers with BRCA
mut. Furthermore, recent preclinical and clinical data suggest that many other types of solid tumors might also benefit from PARP inhibitors, regardless of their BRCA
mut status. Despite this progress, resistance to PARP inhibitors is frequently observed in the clinic, which is, at least in part, due to the incomplete understanding of the mechanism of action of PARP inhibitors. In this review, we summarize the diverse processes underlying the signaling mechanisms of the PARP enzymes. We also discuss recent progress in utilizing these mechanistic insights for overcoming PARP inhibitor resistance, developing predictive biomarker assays, designing rational combination therapies, and, finally, developing the next-generation PARP1-targeting agents with a more complete and durable therapeutic response.
Kinetics of Oxygen Evolution Reaction in Soluble Lead Flow Batteries
Authors: Joy Miji E. , Wills Richard G. A. , Neergat Manoj
Published: December 2024

Kinetics of oxygen evolution reaction (OER) on PbO2 deposited glassy carbon disk electrode in methanesulfonic acid (MSA) is analyzed with cyclic voltammetry and electrochemical impedance spectroscopy for soluble lead flow battery applications. The effect of concentration of the active species (Pb2+) and the electrolyte (MSA) on the OER at the deposited PbO2 layer is investigated. The apparent activation energy of the OER on PbO2, deposited at various overpotentials, is obtained from the Arrhenius and Eyring analyses. The apparent activation energy follows a unique trend that it increases with overpotential, reaches a maximum and decreases thereafter. This is consistent with the PbO2 specifically deposited from MSA of low concentrations (<1 M), where the gel layer composed of hydrated PbO(OH)2 is also found. It is observed that low MSA concentration is preferred for limiting the OER at the positive electrode.
Analysis of the Validity of P2D Models for Solid-State Batteries in a Large Parameter Range
Authors: Sinzig Stephan , Schmidt Christoph P. , Wall Wolfgang A.
Published: December 2024

Simulation models are nowadays indispensable to efficiently assess or optimize novel battery cell concepts during the development process. Electro-chemo-mechano models are widely used to investigate solid-state batteries during cycling and allow the prediction of the dependence of design parameters like material properties, geometric properties, or operating conditions on output quantities like the state of charge. One possibility of classification of these physics-based models is their level of geometric resolution, including three-dimensionally resolved models and geometrically homogenized models, known as Doyle-Fuller-Newman or pseudo two-dimensional models. Within this study, the advantages and drawbacks of these two types of models are identified within a wide range of the design parameter values. Therefore, the sensitivity of an output quantity of the models on one or a combination of parameters is compared. In particular, the global sensitivity, i.e. the sensitivity in a wide range of parameter values, is computed by using the Sobol indexes as a measure. Furthermore, the local sensitivity of the difference in the output quantities of both models is evaluated to identify regions of parameter values in which they contain significant deviations. Finally, remarks on the potential interplay between both models to obtain fast and reliable results are given.
Anodization of Aluminum in a Sodium Hydroxide Solution: Effect of pH on Chemical Dissolution
Authors: Asoh Hidetaka , Fukumoto Shun , Shishido Kaito , Hagiwara Kenta
Published: December 2024

The chemical dissolution of anodic alumina film was investigated using the re-anodization technique. The formation of thick oxide films in an alkaline electrolyte is thought to be difficult to achieve due to the high pH value and high solubility of anodic alumina. The dissolution rate of anodic film was found to be strongly affected by the pH of the solution used for chemical dissolution; the film dissolved significantly faster in a sodium hydroxide solution having a high pH of 13.11 than in acidic solutions commonly used for anodization, such as sulfuric acid (pH 0.98) and phosphoric acid (pH 1.54). Nevertheless, the addition of glycerol to the sodium hydroxide solution effectively suppressed the chemical dissolution of the anodic film. The change in solubility of the anodic alumina film in solution was greatly affected by the change in the dissociation of the solute in solution. The results demonstrated that oxide films more than 10 μm thick were produced in an alkaline electrolyte by adding glycerol to the solution. The suppression of the chemical dissolution of alumina by the addition of alcohol has thus been shown to occur not only in acid solutions but also in alkaline solutions.
Mesoscopic Modelling of Li Deposition in Sulfide-Based Solid Electrolyte Using Two-Dimensional Artificial Polycrystal Structure
Authors: Takagishi Yoichi , Yamaue Tatsuya
Published: December 2024

Understanding Li nucleation and growth mechanism during charging in solid electrolytes (SEs) is essential in development of all-solid-state batteries with metallic Li, because the Li dendrite could cause internal short-circuit by penetration of SE. However, it is still under debate how the factors including degradation of SE layer, the stacking pressure, and the microstructure affect the Li nucleation and growth in SE. In this study, the coupled current-deposition-stress models using the two-dimensional artificial SE structures have been developed by combination of finite element method and Monte Carlo simulations. The model assumed that Li flux on the SE grain induces an eigen strain in the deposited Li region, and Li grows into the SE layer by breaking grain boundary (GB). Degradation of SE was modelled as the decrease of fracture strength of GB using a coefficient. The effects of these microstructure and operation factors on GB fracture and Li deposition have been evaluated and discussed.
Extended Rayleigh Probability Distribution to Higher Dimensions
Authors: Yirsaw Adugna Gelaw , Goshu Ayele Taye
Published: December 2024

In this paper, we have derived and studied new probability distributions by extending the 2‐dimensional Rayleigh distribution (RD). First, we extend the RD to 3 dimensions and then generalize it to k dimensions for any positive integer k ≥ 3. The distributions are named the 3‐dimensional Rayleigh distribution (3‐DRD) and k‐dimensional Rayleigh distribution (k‐DRD), respectively. For both 3‐DRD and k‐DRD, detailed mathematical and statistical properties including derivations of the corresponding cumulative distribution, probability density, survival, and hazard functions, moments, moment generating functions, mode, skewness, kurtosis, and differential entropy are obtained in closed forms. Parameter estimation is done for both models using the maximum likelihood estimation method and some statistical properties of the estimator are discussed for each case. Interestingly, the commonly known Normal, Rayleigh, Maxwell–Boltzmann, chi‐square, gamma, and Erlang distributions are related to the newly developed extended RDs as special cases. For the 3‐DRD, plots of cumulative distribution, probability density, survival, and hazard functions are exhibited, a simulation study is carried out, and random samples are generated using the standard accept–reject (AR) algorithm to check the efficiency of the maximum likelihood estimates of the parameter. Moreover, the new 3‐DRD model is fitted to one simulated and three real datasets, revealing good performance compared to four existing Rayleigh‐based distributions. This study will contribute new knowledge to the field of applied statistics and probability, and the findings will be used as a basis for future research in the field.
Relationships Between Markers of Iron Status and Hematological Parameters in Patients With Sickle Cell Disease
Authors: Parrow Nermi L. , Doherty Jason M. , Conrey Anna , Thein Swee Lay , Fleming Robert E.
Published: December 2024

Based on the relationship between the intracellular concentration of sickle hemoglobin S (HbS) and the delay that occurs prior to the onset of sickling following deoxygenation, targeting the intracellular HbS concentration is a recognized therapeutic approach for sickle cell disease (SCD). We and others have shown that restricting iron by dietary or pharmacologic means improves hematologic parameters, inflammation, and organ damage in mouse models of SCD. Clinical evidence corroborating these findings is confined to case reports and small case series studies, none of which account for treatment or α‐thalassemia. We hypothesize that increased transferrin saturation is associated with increased mean cellular hemoglobin concentration (MCHC) which in turn is associated with decreased red cell counts and worsening anemia. To investigate this hypothesis, we examined the relationships between transferrin saturation and MCHC with each of the parameters that define MCHC in sickle patients (HbSS without α‐thalassemia) and healthy volunteers (HVs). Results indicate that transferrin saturation and MCHC are positively correlated with each other in sickle patients and HV. In patients with SCD, MCHC and transferrin saturation are negatively correlated with RBC count and are not correlated with hemoglobin, whereas each is positively associated with HV. Transferrin saturation and MCHC are each positively correlated with the hemolysis marker, lactate dehydrogenase. These observations support a model where increased transferrin saturation contributes to higher intracellular HbS concentrations with subsequent increases in sickling and hemolysis in sickle patients, suggesting that pharmacologic approaches to decrease serum iron may provide a therapeutic approach for patients with SCD.

Trial Registration: This study was registered with ClinicalTrials.gov identifiers: NCT00011648, NCT00081523, and NCT04817670.
Interference Mechanisms of Endocrine System and Other Systems of Endocrine‐Disrupting Chemicals in Cosmetics—In Vitro Studies
Authors: Zhang Yixuan , Tu Lihong , Chen Jian , Zhou Lihong
Published: December 2024

Endocrine‐disrupting chemicals (EDCs), found in various cosmetic products, interfere with the normal functioning of the endocrine system, impacting hormone regulation and posing risks to human health. Common cosmetic EDCs, such as ultraviolet (UV) filters, parabens, and triclosan, can enter the human body through different routes, including skin absorption. Their presence has been linked to adverse effects on reproduction, immune function, and development. High‐throughput in vitro assays, using various human cell lines, were employed to assess the effects of common cosmetic EDCs such as ethylhexyl methoxycinnamate (EHMC), benzophenone‐3 (BP‐3), homosalate, and parabens. Despite ongoing regulatory efforts, gaps persist in understanding their long‐term impacts, particularly when they are present as mixtures or degradation products in the environment. This study focuses on recent in vitro research to investigate the mechanisms through which cosmetic‐related EDCs disrupt the endocrine system and other physiological systems. The in vitro findings highlight the broader systemic impact of these chemicals, extending beyond the endocrine system to include immune, reproductive, and cardiovascular effects. This research underscores the importance of developing safer cosmetic formulations and enhancing public health protection, emphasizing the need for stricter regulations.
Supplementation of Spirulina (Arthrospira fusiformis) and Oyster Mushroom (Pleurotus ostreatus) at Different Fermentation Stages of Injera, an Ethiopian Fermented Flatbread, Influences Its Nutritional Content, Antioxidant Properties, and Sensory Characteristics
Authors: Zenebe Awoke , Tizazu Abegaz , Ogato Tadesse , Tadesse Abebe , Tesfaye Belayhun , Tesfaw Asmamaw
Published: December 2024

For most Ethiopians, injera is a staple diet, and it is a soft, circular, sour, fermented flat bread that resembles a pancake and is mostly made from teff (Eragrostis tef) and other grains. This study is aimed at evaluating the impact of adding spirulina (Arthrospira fusiformis) and oyster mushrooms (Pleurotus ostreatus) in the three stages of injera fermentation. After baking, the proximate composition, fatty acid profile, mineral analysis, and antioxidant properties were determined. The sensory evaluation of the injera was performed via a 5‐point hedonic measurement. Compared with the 7‐day fermented and unfermented injera, the 2‐day fermented injera with algae and mushrooms contained more protein (119% to 142% increase) and total lipids (30% to 77% increase). Compared with their unfermented and 7‐day fermented counterparts, the mushrooms and algae fermented for 2 days presented greater concentrations of methyl esters of pentadecanoic acid, 14‐methyl‐, 9‐octadecenoic acid (Z)‐, and 9,12‐octadecadienoic acid (Z, Z)‐. The percentage of inhibition of DPPH (2,2‐diphenyl‐1‐picrylhydrazyl) radical was lower in the methanol extracts of the injera that contained unfermented supplements (39%–43%) than in the methanol extracts of the injera that contained 2‐ or 7‐day fermented supplements (73–77%). The injeras that contained only algae (E4, E7, and E10) were selected as their primary choice by the panelists. Adding supplements such as algae and oysters to the injera increased the nutritional content of the injera.
Integrative Approach for the Identification and Delimitation of Orthops Species (Heteroptera, Miridae, and Mirinae) in the Palearctic
Authors: Dzhelali Polina A. , Namyatova Anna A.
Published: December 2024

Orthops is a widely distributed plant bug genus comprising 35 species. Its nominotypical subgenus includes seven species mostly known from the Palearctic, and four of them are widely distributed. Most of them live in sympatry having only little morphological differences. The species limits have never been tested using the molecular data. The aim of this work is to test whether currently defined species represent monophyletic lineages and to find their interrelationships using an integrative approach. Morphological studies on external characters and male and female genitalia were performed. The molecular studies were based on the mitochondrial (cytochrome c oxidase subunit I [COI] and 12S ribosomal RNA [rRNA]) and nuclear (internal transcribed spacer I [ITS1] and calcium ATPase [Ca‐ATPase]) markers and included comparison of the intra‐ and interspecific distances, species delimitation (ABGD, BPP, bGMYC, PTP, and bPTP), and phylogenetic analyses. All markers showed interspecific differences, and COI was the most variable. It was found that all species differed from each other morphologically, and the most reliable character complexes were parameres and female genitalia. In most analyses, Orthops kalmii and O. campestris were monophyletic. Orthops basalis formed a clade in most phylogenetic trees. Most of the species delimitation analyses confirmed the status of those three species. Orthops scutellatus was split into two clades, Palearctic and North American, which was also confirmed by the species delimitation analyses. Those two groups differed in parameres. Orthops campestris and O. scutellatus form a clade in all analyses, and O. basalis forms a clade with O. kalmii in most analyses.
Table S7 from Discovery and Characterization of Brigimadlin, a Novel and Highly Potent MDM2–p53 Antagonist Suitable for Intermittent Dose Schedules
Authors: Gollner Andreas , Rudolph Dorothea , Weyer-Czernilofsky Ulrike , Baumgartinger Rosa , Jung Peter , Weinstabl Harald , Ramharter Jürgen , Grempler Rolf , Quant Jens , Rinnenthal Jörg , Pérez Pitarch Alejandro , Golubovic Bojana , Gerlach Daniel , Bader Gerd , Wetzel Kristiane , Otto Sebastian , Mandl Christian , Boehmelt Guido , McConnell Darryl B. , Kraut Norbert , Sini Patrizia
Published: December 2024

MDM2 mRNA expression, copy number and brigimadlin in vitro activity in MDM2-amplified cell lines versus MDM2 non-amplified cell lines.
Figure S1-3 from Targeting PDHK1 by DCA to Restore NK Cell Function in Hepatocellular Carcinoma
Authors: Yang Xinyi , Liu Yuanyuan , Wang Peng , Li Min , Xiang Tong , Xie Songzuo , Li Minxing , Wang Yan , Weng Desheng , Zhao Jingjing
Published: December 2024

Supplementary materials and legends for supplementary materials
Supp Figure Legends from Immunoproteasome Activation Expands the MHC Class I Immunopeptidome, Unmasks Neoantigens, and Enhances T-cell Anti-Myeloma Activity
Authors: Rana Priyanka S. , Ignatz-Hoover James J. , Guo Chunna , Mosley Amber L. , Malek Ehsan , Federov Yuriy , Adams Drew J. , Driscoll James J.
Published: December 2024

Supplementary Figure Legends
Supplemental Fig. S7 from Trametinib Potentiates Anti-PD-1 Efficacy in Tumors Established from Chemotherapy-Primed Pancreatic Cancer Cells
Authors: Pham Thao D. , Metropulos Anastasia E. , Mubin Nida , Becker Jeffrey H. , Shah Dhavan , Spaulding Christina , Shields Mario A. , Bentrem David J. , Munshi Hidayatullah G.
Published: December 2024

Supplemental Fig. S7. Trametinib is the most effective MEK inhibitor at blocking ERK phosphorylation in the KPC and KPC-FIO cells. A-C. 2138 and 2138-FIO (A), 3886 and 3886-FIO (B), and 3213 and 3213-FIO (C) cells were treated with vehicle control (-, DMSO), U0126 (2 µM, U), Binimetinib (2 µM, B), Cobimetinib (2 µM, C), Selumetinib (2 µM, S), or Trametinib (2 µM, T). After 2 and 24 hours, the cells were collected and analyzed for p-ERK1/2 and total ERK1/2 by western blotting with HSP90 as loading control. Blots are representative of three independent replicates.
Data from TR-107, an Agonist of Caseinolytic Peptidase Proteolytic Subunit, Disrupts Mitochondrial Metabolism and Inhibits the Growth of Human Colorectal Cancer Cells
Authors: Giarrizzo Michael , LaComb Joseph F. , Patel Hetvi R. , Reddy Rohan G. , Haley John D. , Graves Lee M. , Iwanowicz Edwin J. , Bialkowska Agnieszka B.
Published: December 2024

Abstract
Oxidative phosphorylation is an essential metabolic process for cancer proliferation and therapy resistance. The ClpXP complex maintains mitochondrial proteostasis by degrading misfolded proteins. Madera Therapeutics has developed a class of highly potent and selective small-molecule activators (TR compounds) of the ClpXP component caseinolytic peptidase proteolytic subunit (ClpP). This approach to cancer therapy eliminates substrate recognition and activates nonspecific protease function within mitochondria, which has shown encouraging preclinical efficacy in multiple malignancies. The class-leading compound TR-107 has demonstrated significantly improved potency in ClpP affinity and activation and enhanced pharmacokinetic properties over the multitargeting clinical agent ONC201. In this study, we investigate the in vitro efficacy of TR-107 against human colorectal cancer cells. TR-107 inhibited colorectal cancer cell proliferation in a dose- and time-dependent manner and induced cell cycle arrest at low nanomolar concentrations. Mechanistically, TR-107 downregulated the expression of proteins involved in the mitochondrial unfolded protein response and mitochondrial DNA transcription and translation. TR-107 attenuated oxygen consumption rate and glycolytic compensation, confirming inactivation of oxidative phosphorylation and a reduction in total cellular respiration. Multiomics analysis of treated cells indicated a downregulation of respiratory chain complex subunits and an upregulation of mitophagy and ferroptosis pathways. Further evaluation of ferroptosis revealed a depletion of antioxidant and iron toxicity defenses that could potentiate sensitivity to combinatory chemotherapeutics. Together, this study provides evidence and insight into the subcellular mechanisms employed by colorectal cancer cells in response to potent ClpP agonism. Our findings demonstrate a productive approach to disrupting mitochondrial metabolism, supporting the translational potential of TR-107.
Data from Preclinical Characterization of ARX517, a Site-Specific Stable PSMA-Targeted Antibody–Drug Conjugate for the Treatment of Metastatic Castration-Resistant Prostate Cancer
Authors: Skidmore Lillian K. , Mills David , Kim Ji Young , Knudsen Nick A. , Nelson Jay D. , Pal Manoj , Wang Jianing , GC Kedar , Gray Michael J. , Barkho Wisam , Nagaraja Shastri Prathap , Ramprasad Mysore P. , Tian Feng , O’Connor Daniel , Buechler Ying J. , Zhang Shawn Shao-Hui
Published: December 2024

Abstract
Metastatic castration-resistant prostate cancer (mCRPC) is an advanced disease in which patients ultimately fail standard-of-care androgen deprivation therapies and exhibit poor survival rates. The prostate-specific membrane antigen (PSMA) has been validated as an mCRPC tumor antigen with overexpression in tumors and low expression in healthy tissues. Using our proprietary technology for incorporating synthetic amino acids into proteins at selected sites, we have developed ARX517, an antibody–drug conjugate composed of a humanized anti-PSMA antibody site-specifically conjugated to a tubulin inhibitor at a drug-to-antibody ratio of 2. After binding PSMA, ARX517 is internalized and catabolized, leading to cytotoxic payload delivery and apoptosis. To minimize premature payload release and maximize delivery to tumor cells, ARX517 employs a noncleavable polyethylene glycol linker and stable oxime conjugation enabled via synthetic amino acid protein incorporation to ensure its overall stability. In vitro studies demonstrate that ARX517 selectively induces cytotoxicity of PSMA-expressing tumor cell lines. ARX517 exhibited a long terminal half-life and high serum exposure in mice and dose-dependent antitumor activity in both enzalutamide-sensitive and -resistant cell line–derived xenograft and patient-derived xenograft models of prostate cancer. Repeat-dose toxicokinetic studies in nonhuman primates demonstrated that ARX517 was tolerated at exposures well above therapeutic exposures in mouse pharmacology studies, indicating a wide therapeutic index. In summary, ARX517 inhibited tumor growth in diverse mCRPC models, demonstrated a tolerable safety profile in monkeys, and had a wide therapeutic index based on preclinical exposure data. Based on the encouraging preclinical data, ARX517 is currently being evaluated in a phase I clinical trial (NCT04662580).
Table S3 from Ruthenium Drug BOLD-100 Regulates BRAFMT Colorectal Cancer Cell Apoptosis through AhR/ROS/ATR Signaling Axis Modulation
Authors: Griffin Daryl , Carson Robbie , Moss Debbie , Sessler Tamas , Lavin Deborah , Tiwari Vijay K. , Karelia Shivaali , Kennedy Richard , Savage Kienan I. , McDade Simon , Carie Adam , Pankovich Jim , Bazett Mark , Van Schaeybroeck Sandra
Published: December 2024

Table S3: GSE59857 ssGSEA Hallmarks
Supplementary Figure 4 from Ruthenium Drug BOLD-100 Regulates BRAFMT Colorectal Cancer Cell Apoptosis through AhR/ROS/ATR Signaling Axis Modulation
Authors: Griffin Daryl , Carson Robbie , Moss Debbie , Sessler Tamas , Lavin Deborah , Tiwari Vijay K. , Karelia Shivaali , Kennedy Richard , Savage Kienan I. , McDade Simon , Carie Adam , Pankovich Jim , Bazett Mark , Van Schaeybroeck Sandra
Published: December 2024

Treatment of BRAFMT CRC in vitro and mouse models with BOLD-100, AZD6738 or combination.
Supplementary Figure Legends from LRRC75A-AS1 Drives the Epithelial–Mesenchymal Transition in Cervical Cancer by Binding IGF2BP1 and Inhibiting SYVN1-Mediated NLRP3 Ubiquitination
Authors: Sui Hongying , Shi Caixia , Yan Zhipeng , Chen Jinyang , Man Lin , Wang Fang
Published: December 2024

Supplementary Figure Legends 1-2.
Supplementary Figure 2 from LRRC75A-AS1 Drives the Epithelial–Mesenchymal Transition in Cervical Cancer by Binding IGF2BP1 and Inhibiting SYVN1-Mediated NLRP3 Ubiquitination
Authors: Sui Hongying , Shi Caixia , Yan Zhipeng , Chen Jinyang , Man Lin , Wang Fang
Published: December 2024

Supplementary Figure 2. The schematic diagram of this study. LRRC75A-AS1 competitively binds to IGF2BP1 protein to destabilize SYVN1 mRNA, inhibits SYVN1-mediated NLRP3 ubiquitination and activates IL-1β/Smad2/3 signaling, thereby promoting EMT in cervical cancer.
Supplementary Table 9 from EHMT1/2 Inhibition Promotes Regression of Therapy-Resistant Ovarian Cancer Tumors in a CD8 T-cell–Dependent Manner
Authors: Nguyen Lily L. , Watson Zachary L. , Ortega Raquel , Woodruff Elizabeth R. , Jordan Kimberly R. , Iwanaga Ritsuko , Yamamoto Tomomi M. , Bailey Courtney A. , To Francis , Lin Shujian , Villagomez Fabian R. , Jeong Abigail D. , Guntupalli Saketh R. , Behbakht Kian , Gibaja Veronica , Arnoult Nausica , Chuong Edward B. , Bitler Benjamin G.
Published: December 2024

Hallmark pathways enriched in ID8-R cells treated with combinatory UNC0642/Olaparib compared to Olaparib alone.
Supplementary Figure 3 from EHMT1/2 Inhibition Promotes Regression of Therapy-Resistant Ovarian Cancer Tumors in a CD8 T-cell–Dependent Manner
Authors: Nguyen Lily L. , Watson Zachary L. , Ortega Raquel , Woodruff Elizabeth R. , Jordan Kimberly R. , Iwanaga Ritsuko , Yamamoto Tomomi M. , Bailey Courtney A. , To Francis , Lin Shujian , Villagomez Fabian R. , Jeong Abigail D. , Guntupalli Saketh R. , Behbakht Kian , Gibaja Veronica , Arnoult Nausica , Chuong Edward B. , Bitler Benjamin G.
Published: December 2024

Transcriptomics analysis of EZM8266 treatment.
Supplementary Table S2 from Construction and Validation of a Novel Forecasting Nomogram to the Risk of Colorectal Adenomas: Preventing Colorectal Cancer at Its Origin
Authors: Li Mao , Cui Mingyu , Zhou Xiaobin , Song Ying
Published: December 2024

Supplementary Table S2: Baseline clinical characteristics of participants in the training and validation cohorts
Supplementary Movie 2 from Targeting BTN2A1 Enhances Vγ9Vδ2 T-Cell Effector Functions and Triggers Tumor Cell Pyroptosis
Authors: Le Floch Anne-Charlotte , Imbert Caroline , Boucherit Nicolas , Gorvel Laurent , Fattori Stéphane , Orlanducci Florence , Le Roy Aude , Archetti Lorenzo , Crescence Lydie , Panicot-Dubois Laurence , Dubois Christophe , Vey Norbert , Briantais Antoine , Anastasio Amandine , Cano Carla , Guittard Geoffrey , Frechin Mathieu , Olive Daniel
Published: December 2024

Visualization of Vγ9Vδ2 T cells (E) and SUP-T1 (T) coculture using a label-free method within 20 hours. Ratio T/E = 1/2. Cells treated with 107G3B5 antibody (10ug/ml).
Figure S4 from CAR T Cells Engineered to Secrete IFNκ Induce Tumor Ferroptosis via an IFNAR/STAT1/ACSL4 Axis
Authors: Gao Yaoxin , Liu Shasha , Huang Yifan , Wang Hui , Zhao Yuyu , Cui Xuyang , Peng Yajing , Li Feng , Zhang Yi
Published: December 2024

Expression of mRNA and proteins of ACSL4, IFNAR1, IFNAR2, and STAT1.
Supplementary Figure 5 from Cannabidiol Enhances Atezolizumab Efficacy by Upregulating PD-L1 Expression via the cGAS–STING Pathway in Triple-Negative Breast Cancer Cells
Authors: Kim Bu Gyeom , Kim Bo Ram , Kim Dae Yeong , Kim Woo Young , Kang Sanghee , Lee Sun Il , Oh Sang Cheul
Published: December 2024

Synergistic effects of CBD and anti-PD-L1 mAb in vivo experiments
Table S2 from Inflammation Mediated by Gut Microbiome Alterations Promotes Lung Cancer Development and an Immunosuppressed Tumor Microenvironment
Authors: Rahal Zahraa , Liu Yuejiang , Peng Fuduan , Yang Sujuan , Jamal Mohamed A. , Sharma Manvi , Moreno Hannah , Damania Ashish V. , Wong Matthew C. , Ross Matthew C. , Sinjab Ansam , Zhou Tieling , Chen Minyue , Tarifa Reischle Inti , Feng Jiping , Chukwuocha Chidera , Tang Elizabeth , Abaya Camille , Lim Jamie K. , Leung Cheuk Hong , Lin Heather Y. , Deboever Nathaniel , Lee Jack J. , Sepesi Boris , Gibbons Don L. , Wargo Jennifer A. , Fujimoto Junya , Wang Linghua , Petrosino Joseph F. , Ajami Nadim J. , Jenq Robert R. , Moghaddam Seyed Javad , Cascone Tina , Hoffman Kristi , Kadara Humam
Published: December 2024

Comparative analysis of microbial abundance in murine fecal samples across FMT groups.
Figure S8 from Peripheral Blood–Derived PD-1/CD28–CD19 CAR–Modified PD-1+ T-Cell Therapy in Patients with Solid Tumors
Authors: Zhang Zhen , Zhao Xuan , Zhao Qitai , Chen Xinfeng , Li Congcong , Liu Yaqing , Shen Chunyi , Song Lijie , Miao Lijun , Guo Fuyou , Mou Xiaoning , Zhao Jie , Gu Weiyue , Zhang Yi
Published: December 2024

Supplementary Figure S8. Levels of CAR-T cells and B cells in PB after cell infusion.
Figure S13 from CD91 and Its Ligand gp96 Confer Cross-Priming Capabilities to Multiple APCs during Immune Responses to Nascent, Emerging Tumors
Authors: Nayak Devanshi A. , Sedlacek Abigail L. , Cillo Anthony R. , Watkins Simon C. , Binder Robert J.
Published: December 2024

Supplementary Figure 13. Transfer of gp96-EGFP by CD11c+ CD11b- donors.
Supplementary Table S12 from Spatially Resolved Whole-Transcriptomic and Proteomic Profiling of Lung Cancer and Its Immune Microenvironment According to PD-L1 Expression
Authors: Koh Jaemoon , Lee Dongjoo , Kim Sehui , Song Seung Geun , Han Bogyeong , Jeong Hyein , Kim Young A , Keam Bhumsuk , Lee Se-Hoon , Kim Kwangsoo , Jeon Yoon Kyung , Chung Doo Hyun
Published: December 2024

The most up- or downregulated gene sets in tumor cells between ID_PDL1H and ID_PDL1L
Figure S5 from Hyper-Interferon Sensitive Influenza Induces Adaptive Immune Responses and Overcomes Resistance to Anti–PD-1 in Murine Non–Small Cell Lung Cancer
Authors: Du Yushen , Salehi-Rad Ramin , Zhang Tian-hao , Crosson William P. , Abascal Jensen , Chen Dongdong , Shi Yuan , Jiang Hong , Tseng Yen-Wen , Ma Xi , Hong Mengying , Wang Sihan , Wang Xijuan , Tang Kejun , Hu Shiyao , Li Yuting , Ni Shaokai , Cai Yiqi , Tappuni Shahed , Shen Yong , Liu Bin , Sun Ren
Published: December 2024

Assessment of synergy and flow phenotyping of immune cells following combination therapy
Data from Targeting BTN2A1 Enhances Vγ9Vδ2 T-Cell Effector Functions and Triggers Tumor Cell Pyroptosis
Authors: Le Floch Anne-Charlotte , Imbert Caroline , Boucherit Nicolas , Gorvel Laurent , Fattori Stéphane , Orlanducci Florence , Le Roy Aude , Archetti Lorenzo , Crescence Lydie , Panicot-Dubois Laurence , Dubois Christophe , Vey Norbert , Briantais Antoine , Anastasio Amandine , Cano Carla , Guittard Geoffrey , Frechin Mathieu , Olive Daniel
Published: December 2024

Abstract
Vγ9Vδ2 T cells are potent but elusive cytotoxic effectors. Butyrophilin subfamily 2 member A1 (BTN2A1) is a surface protein that has recently been shown to bind the Vγ9 chain of the γδ T-cell receptor, but its precise role in modulating Vγ9Vδ2 T-cell functions remains unknown. Here, we show that 107G3B5, a monoclonal BTN2A1 agonist antibody, was able to significantly enhance Vγ9Vδ2 T-cell functions against hematologic or solid cell lines and against primary cells from patients with adult acute lymphoblastic leukemia. New computer vision strategies applied to holotomographic microscopy videos showed that 107G3B5 enhanced the interaction between Vγ9Vδ2 T cells and target cells in a quantitative and qualitative manner. In addition, we found that Vγ9Vδ2 T cells activated by 107G3B5 induced caspase 3/7 activation in tumor cells, thereby triggering tumor cell death by pyroptosis. Together, these data demonstrate that targeting BTN2A1 with 107G3B5 enhances the Vγ9Vδ2 T-cell antitumor response by triggering pyroptosis-induced immunogenic cell death. These new pyroptosis-based therapies have great potential to stimulate the immune system to fight cancer, especially “cold” tumors.

See related Spotlight by Kabelit, p. 1662
Screening for TSEN54 Variants in Egyptian Patients with Pontocerebellar Malformations
Authors: Emam Bayoumi A. , Abdel-Hamid Mohamed S. , Eid Maha , Girgis Marian , Ragab Omar A. , Zaki Maha S. , El-Kiki Hassan , Abdel-Hady Sawsan , Abdel-Salam Ghada M.H.
Published: December 2024

Introduction: Pontocerebellar hypoplasia (PCH) represents a group of rare disorders with prenatal onset and time-dependent loss of brain parenchyma, predominantly affecting the cerebellum and pons with variable involvement of supratentorial structures. Radiologically and pathologically, they are characterized by small cerebellum and pons. Our study aimed to screen for the TSEN54 gene variants in Egyptian patients with PCH for proper counseling and to describe the brain MRI and the clinical phenotype and compare, them to those described in the literature. Methods: Thirty patients from thirty Egyptian families with a diagnosis of PCH based on neuroimaging findings were selected. Clinical evaluation, radiological findings, and genetic investigations were done for all patients. Results: The common missense variant c.919G>T (p.A307S) was identified in only 6 patients from six unrelated families (6/30; 20%) who showed different degrees of pontocerebellar malformations on brain imaging. Conclusion: The presence of a dragonfly/butterfly-like pattern in the coronal section of the cerebellum recommends genetic testing of TSEN54 as a first step. For negative cases, whole-exome sequencing is essential to reach a definite diagnosis and determine the etiology.
Whole Exome Sequencing of a Multiplex Family of Indian Origin Identifies Variants in the RAI1 and FLII Genes within the 17p11.2 Region in Siblings with Autism and Smith Magenis Syndrome
Authors: Srividhya Durbagula , Parambath Snijesh Valiya , Sathyanarayanan Ranganayaki , Huligerepura Sosalegowda Aparna , Korlimarla Aruna , Niranjana Murthy Ashitha S. , Prabhakaran Nishant , Vijayanand Meghana , Gowda Naveen Kumar Chandappa
Published: December 2024

Introduction: Autism spectrum disorders (ASDs) are complex neurodevelopmental disorders characterized by restrictive repetitive behavior and impairment in social and communication skills. They are extremely heterogeneous with a strong genetic preponderance. They are clinically highly convoluted, presenting with multiple comorbid conditions and syndromic features. More than 100 genes have been identified to date. Method: Whole exome sequencing (WES) has emerged as a valuable tool in evaluating the genetic underpinnings of ASDs, be it the syndromic or the idiopathic variants. In the current study, we performed WES on a multiplex family of Indian origin to investigate the disease etiology in the siblings (S1 [Female] and S2 [Male]) exhibiting ASD syndromic features, at both clinical and genetic aspects. Results: Exome sequencing identified a missense variant (NM_030665.4:c.5320C>T; p.Arg1774Trp) in S1 resulting in RAI1 haploinsufficiency. Validation by Sanger sequencing confirmed that the variant was true positive and maternally transmitted in the subject. Likewise, we report an inherited missense variant at the same locus (17p11.2) corresponding to the FLII gene (NM_002018.4:c.2030A>C; p.Glu677Ala) in the other sibling, S2. Both the variants were reported in the Smith Magenis syndrome (SMS) critical region justifying their contribution to the presentation of the syndromic SMS features. These WES findings were consistent with the clinical findings that imply SMS features in both siblings. Conclusion: The current study employed WES to provide insights into the genetic complexity associated with syndromic ASD and how that contributes to the disease heterogeneity. Moving forward, combinatorial approaches and findings from syndromic ASDs can potentially act as indicators to understand the genetic and phenotypic variations seen in idiopathic ASD.
Unveiling a Rarity: First Instance of Urinary Tract Infection Caused by Corynebacterium tuberculostearicum in India
Authors: Kundu Aditya , Ghosh Nirmalya , Sengupta Mallika , Chatterjee Shiv Sekhar
Published: December 2024

Introduction: Corynebacterium species other than C. diphtheriae are being continuously reported as pathogens. Case Presentation: A patient visited the Urology Outpatient Department of a tertiary care centre in India reporting lower abdominal pain, urinary incontinence, and intermittent weak urine flow persisting for 12 years, intensifying over the last 15 days. She also experienced urgency, straining, weak stream, and incomplete voiding, along with a previous fever episode. The patient had a medical record of multiple urethral dilations and surgeries since 2014, with the most recent urethral dilatation in July 2023. Diagnostic tests revealed a thickened bladder with notable post-void residual urine. Uroflowmetry indicated obstructive uropathy. Urine analysis exhibited elevated leucocytes, epithelial cells, red blood cells, and abundant bacilli. Corynebacterium tuberculostearicum was identified through matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) following three pure growths of Gram-positive bacilli in urine cultures. The organism showed sensitivity to cotrimoxazole and tetracyclines. Treatment with doxycycline significantly improved the symptoms. Conclusion: The organism Corynebacterium tuberculostearicum is a very rare cause of UTI and the patient responded well to treatment.
Warm Autoimmune Hemolytic Anemia as First Presentation of Chronic Myeloid Leukemia: A Case Report
Authors: Tawalbeh Ahmad , Al-Mashdali Abdulrahman , Al-Sabbagh Ahmad , Ellahi Anil Y. , Yassin Mohamed A.
Published: December 2024

Introduction: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the Philadelphia chromosome and uncontrolled granulocyte production. While autoimmune hemolytic anemia (AIHA) is commonly associated with lymphoproliferative disorders such as chronic lymphocytic leukemia, its occurrence in CML is rare, with only a few documented cases. Here, we report a case of concurrent chronic-phase CML and AIHA. Case Presentation: We present a 34-year-old female diagnosed with warm AIHA as the first presentation of CML. Diagnostic workup, including peripheral smear, revealed hemolysis with elevated lactate dehydrogenase and a positive direct antiglobulin test (DAT), along with a positive Philadelphia chromosome, confirming CML. Steroid therapy successfully managed the AIHA, leading to normalization of hemoglobin levels and subsequent tapering and discontinuation of steroids. Conclusion: While AIHA is a rare cause of anemia in CML, it should be considered during anemia evaluation, particularly in cases of CML relapse.
Global estimates of vaccine-associated hepatic autoimmune disorders and their related vaccines, 1968-2024: An international analysis of the WHO pharmacovigilance database
Authors: Jeong Jinyoung , Jo Hyesu , Park Jaeyu , Smith Lee , Rahmati Masoud , Lee Kwanjoo , Ha Yeonjung , Yon Dong Keon
Published: December 2024

Previous studies have suggested an association between vaccines and autoimmune diseases, but they were limited by their narrow focus and timeframe. Therefore, this study conducted the first large-scale international analysis to investigate the impact of various vaccines on autoimmune liver diseases. Utilizing WHO’s VigiBase data from 1968 to 2024, the study identified 1,083 (0.012%) cases of vaccine-associated hepatic autoimmune disorders out of 8,562,584 reported vaccine adverse events. The vaccines with the highest risk of hepatic autoimmune disorders were the hepatitis B vaccine (reporting odds ratio [ROR], 3.52; 95% CI, 2.50-4.95), COVID-19 mRNA vaccines (ROR, 2.95; 95% CI, 2.73-3.18), and papillomavirus vaccines (ROR, 2.13; 95% CI, 1.45-3.13). Additionally, when vaccine-associated hepatic autoimmune disorders occurred, hepato-biliary adverse events were frequently observed to occur concurrently. This study suggests that vaccines may induce hepatic autoimmune disorders and highlights the need for enhanced monitoring before and after vaccination. Additionally, it proposes implementing pre-vaccination screening protocols and post-vaccination monitoring to address this concern.
Status of inpatients with pediatric epilepsy in children’s hospitals in China (2016–2021)
Authors: Wang Jiaqi , Liu Tinghong , Xu Hui , Feng Guoshuang , Wang Yangshuo , Cao Dezhi , Wei Zhirong , Kuang Suhui , Wei Haihua , Chen c , Xu Jinshan , Zhai Feng , Liang Shuli
Published: December 2024

Background: Pediatric epilepsy is the most common disease of pediatric neurological diseases in China. Current demographic characteristics and economic burdens are needed to guide public health policy. In this study, we provide the demographic characteristics and economic burden of pediatric epilepsy patients in China from 2016 to 2021, and describe the change trend and correlation of demographic characteristics and economic burden by province.
Methods: Using data from the Futang Research Center of Pediatric Development, we conducted a demographic-based cross-sectional study of pediatric epilepsy patients in 29 children’s hospitals in China to assess changes in the distribution and economic burden over 6 years and related factors. We obtained per capita disposable income information from the Economic Statistical Bulletin of the National Bureau of Statistics of China and the statistical bureaus of provincial administrative regions. Demographic, diagnostic classification proportion and distribution trends, and economic burden from 2016 to 2021 were verified for pediatric patients with epilepsy.
Results: From 2016 to 2021, there were 149,375 patients diagnosed with epilepsy. The proportion of patients younger than 3 years decreased significantly from 51.13% to 29.43% (P=0.00853, R2=0.9803). The root-mean-square-error between the Inter-Provincial Visits Indexes decreased from 1.70 to 0.90, decreasing significantly (R2=0.8306). The disease burden decreased from 17.26% to 12.11% with a significant upward trend (P=0.02417, R2=0.8817). A negative correlation between disease burden and the Inter-Provincial Visits Index (P=0.0383) was observed, along with a positive correlation with the proportion of patients younger than 3 years old (P<0.0001).
Conclusions: From 2016 to 2021, the proportion of young patients, population mobility and economic burden on patients decreased, and healthcare level of pediatric epilepsy improved. In addition, based on the current observations, the healthcare level of pediatric epilepsy in Western and Central China is lower than in other regions, and the economic burden on patients is higher than in other regions. In the future, these areas require higher priority concerning policy and financial support.
Association of serum ferritin with total and regional fat measured by dual-energy X-ray absorptiometry in a nationally representative survey
Authors: Chen Yuan , Wang Chao , Xiao Yanyan , Hu Tian , Yang Xuerong , Mu Guohua , Lu Hao , Xu Junfei , Chen Chi
Published: December 2024

Introduction: Fat distribution is a stronger predictor for cardiometabolic morbidity and mortality. We aimed to investigate the association of elevated iron stores, measured as serum ferritin levels, with total and regional body fat.
Methods: Data from 2,646 adults from the National Health and Nutrition Examination Survey 2017–2018 was analyzed. Dual-energy X-ray absorptiometry was used to measure overall and regional body fat. The fat mass index (FMI) was calculated by dividing the fat mass (kg) by the square of body height (m²). The leg fat mass to trunk fat mass ratio (LTR) was used to assess the relative distribution of leg fat compared to trunk fat.
Results: Medians (IQR) of serum ferritin levels were 0.168 μg/mL (0.104–0.269) for men and 0.053 μg/mL (0.026–0.102) for women. After adjusting for sociodemographic, lifestyle, and metabolic factors, serum ferritin showed a significant positive association with total FMI (β=2.662) and trunk FMI (β=0.983), and a negative association with leg FMI (β=-0.324) and LTR (β=-0.160) in men. In women, serum ferritin showed a significant positive association with total FMI (β=4.658), trunk FMI (β=2.085), and negative association with LTR (β=-0.312). Significant positive trends were observed for serum ferritin with total and trunk FMI in men and women, using the lowest serum ferritin quartile as the reference group. Additionally, significant negative trends were observed for serum ferritin with leg FMI and LTR in men. The mediation analysis revealed that C-reactive protein mediated 16.4% and 22.6% of the potential effects of serum ferritin on trunk FMI in men and women, respectively.
Conclusion: Higher ferritin levels were associated with greater total and trunk fat but lower leg fat. Further prospective and mechanistic studies are warranted to confirm the study results.
Prophylaxia das Doenças Venereas
Authors: Rabello Eduardo
Published: December 2024

Foi com o maior empenho e satisfação que, cumprindo as amaveis imposições do convite do sr. prof. Smillie, aqui estou para fazer uma conferencia sibre a prophylaxia du doenças veoereu. Não é necessario justificar, senão apenas applaudir, a razão de institutos desta natureza reconhecidos de grande utilidade em diversas nações, onde o ensino de hygiene vão merecendo cada vez mais attenção.
Investigações sobre a uncinariose
Authors: Smillie Wison G.
Published: December 2024

Durante os doís ultimos annos, o lnstitnto de Hygiene da Faculdade de Medicina de S. Paulo se dedicou ao estudo de certos problemas referentes á technica da diagnose e tratamento da uncinariose. Durante esses trabalhos, collecionaram-se cuidadosamente dados sobre todos os doentes tratados, tornando assim evidentes certos princípios relativos á natureza da uncinariose, principias esses que concordam perfeitamente com os nossos conhecimentos theoricos sobre a biologia do parasito, mas differem algum tanto das concepções populares sobre esta molestia.
A educação hygienica na escola
Authors: Guerner Nuno
Published: December 2024

A saude é um ideal positivo e, com esse caracter, deve ser realçada para a infancia. A melhor época para o ensino da hygiene e para a formação de habitas hygienicos é a dos primeiros annos da existencia. Duas razões bem ponderaveis sustentam esse enunciado: Primeiro, porque a educação é mais productiva na infancia; depois, pelo facto de se fazer, nessa epoca da vida, uma semeadura em espíritos virgens, ainda livres da obra demolidora do meio. Já um velho brocardo dizia da facilidade com que os princípios e costumes adquiridos nos primeiros períodos da existencia nunca mais ou muito difficilmente podem ser perdidos ou afastados.
Contribuição ao estudo das reacções biologicas na Cysticercose.
Authors: Silveira Gestão Fleury da , Pessôa Sarnual B. , Corrêa Clovis
Published: December 2024

O diagnosticc da cysticercose no laboratorio é feito principalmente por meio da reacção do desvio do complemento. Em geral o antígeno usado é constituído por um extracto total aquoso de cysticercus. Outras reacções taes como a precipitoreacção e augmento da taxa dos eosinophilos no sangue apresentam sómente um valor relativo.
Tentativa de Selecção Profissional
Authors: Camargo Monteiro de
Published: December 2024

A Escola Profissional Mecanica do Lyceu de Artes e Officios de S. Paulo na sua organisação previu um gabinete de Psychtechinia destinado a coadjuvar com os seus methodos a formação de operarios mecanicos com o approveitamento maximo de suas faculdades.