bluuebunny/crossref_metadata_2025 huggingface dataset:
Water Sensitivity and Structural Properties of Loess
Authors: Zhang Longfei , Hu Zaiqiang , Li Hongru , She Haicheng , Wang Xiaoliang , Yang Xi , Han Xiaoning
Published: May 2024

Loess has unique water sensitivity due to its distinct formation environment. The structure of loess is undercompactness, weak cementation, and porousness. The water sensitivity of loess directly leads to many environmental problems and geological hazards, including subgrade subsidences, slope collapse or failures, and building cracking. To reveal the relationship between water sensitivity and loess structure, confined‐compression collapsibility tests and triaxial‐collapsibility tests were performed on loess in different areas. The collapsibility coefficient, porosity ratio, and collapsibility rate were analyzed. Results show that the collapsibility process of loess can be divided into three stages: wetting, softening, and settling. The collapsibility sensitivity of loess is determined primarily by its structural and hydraulic state.
Finite Difference Method for Infection Model of HPV with Cervical Cancer under Caputo Operator
Authors: Bajjah Bushra , Modanli Mahmut
Published: May 2024

In this paper, a fractional model in the Caputo sense is used to characterize the dynamics of HPV with cervical cancer. Generalized mean value theorem has been used to examine whether the infection model has a unique positive solution. The model has two equilibrium points: the disease‐free point and the endemic point. The examination of the system’s local and global stability is provided in terms of the basic reproductive number . The global stability analysis has been carried out using an appropriate Lyapunov function and the LaSalle invariant principle. The results demonstrate that in the infection model, if , then the solution converges to the disease‐free equilibrium, which is both locally and globally asymptotically stable. Whilst , the endemic equilibrium is considered to exist. Simulations are implemented via a finite difference method with Grünwald‐Letnikov discretization approach for Caputo derivative operator to define how changes in parameters impact the dynamic behavior of the system using Matlab.
Antibiotic Resistance Profile of Staphylococcus aureus in Cancer Patients at Laquintinie Hospital in Douala, Littoral Region, Cameroon
Authors: Kengne Michael Francis , Mbaveng Armelle T. , Kuete Victor
Published: May 2024

Cancer and chemotherapy predispose the patients to various bacterial infections. This study is aimed at isolating and establishing the distribution of antibiotic-resistant Staphylococcus aureus from fecal samples in subjects with cancer admitted to the Oncology Department at Laquintinie Hospital in Douala, in the Littoral Region of Cameroon. A cross-sectional study was conducted from October 2021 to March 2023. Cancer and noncancer patients were suffering from Staphylococcus aureus infection. The isolation of Staphylococcus aureus was based on culture on the specific medium. The Kirby-Bauer disk diffusion method was used for drug susceptibility testing. Of the 507 patients studied, 307 (60.55%) were cancer patients, compared to 200 (39.45%) noncancer patients. S. aureus was isolated in 81 (15.97%) participants, among which 62 (76.55%) were cancer patients and 19 (23.45%) were noncancer patients. In the study population, 31.92% of participants had breast cancer, followed by cervical cancer (13.68%) and leukemia (7.17%). Staphylococcus aureus isolates showed high resistance rates in cancer patients compared to noncancer patients to amoxicillin-clavulanic acid (AMC, 77.42% versus 31.58%), cefoxitin (FOX, 80.65% versus 63.16%), ciprofloxacin (CIP, 75.81% versus 26.32%), ofloxacin (OFX, 69.35% versus 31.58%), fusidic acid (FUS, 70.97% versus 53.63%), and tetracycline (TET, 85.48% versus 78.95%). Staphylococcus aureus showed a significant increase in multidrug-resistant (MDR) and methicillin-resistant (MRSA) phenotypes in cancer patients compared to noncancer patients (p<0.05). The prevalence of MRSA was 76.54%, higher than that of methicillin-sensitive Staphylococcus aureus (MSSA) (23.46%). The frequency of MRSA was significantly higher (p<0.001) in cancer patients (80.65%) than in noncancer patients (19.35%). This study showed that there is an association between antibiotic resistance and cancer status. Research and interventions must be focused on the cancer population to combat the appearance of MDR bacteria due to the loss of effectiveness of antibiotics.
Novel Biomarkers for Alzheimer’s Disease: Plasma Neurofilament Light and Cerebrospinal Fluid
Authors: Abukuri Daniel Naawenkangua
Published: May 2024

Neurodegenerative disorders such as Alzheimer’s disease (AD) represent an increasingly significant public health concern. As clinical diagnosis faces challenges, biomarkers are becoming increasingly important in research, trials, and patient assessments. While biomarkers like amyloid-β peptide, tau proteins, CSF levels (Aβ, tau, and p-tau), and neuroimaging techniques are commonly used in AD diagnosis, they are often limited and invasive in monitoring and diagnosis. For this reason, blood-based biomarkers are the optimal choice for detecting neurodegeneration in brain diseases due to their noninvasiveness, affordability, reliability, and consistency. This literature review focuses on plasma neurofilament light (NfL) and CSF NfL as blood-based biomarkers used in recent AD diagnosis. The findings revealed that the core CSF biomarkers of neurodegeneration (T-tau, P-tau, and Aβ42), CSF NFL, and plasma T-tau were strongly associated with Alzheimer’s disease, and the core biomarkers were strongly associated with mild cognitive impairment due to Alzheimer’s disease. Elevated levels of plasma and cerebrospinal fluid NfL were linked to decreased [18F]FDG uptake in corresponding brain areas. In participants with Aβ positivity (Aβ+), NfL correlated with reduced metabolism in regions susceptible to Alzheimer’s disease. In addition, CSF NfL levels correlate with brain atrophy and predict cognitive changes, while plasma total tau does not. Plasma P-tau, especially in combination with Aβ42/Aβ40, is promising for symptomatic AD stages. Though not AD-exclusive, blood NfL holds promise for neurodegeneration detection and assessing treatment efficacy. Given the consistent levels of T-tau, P-tau, Aβ42, and NFL in CSF, their incorporation into both clinical practice and research is highly recommended.
Investigation of Engineering Properties and Solidification Mechanism of Loess by Sodium Silicate Alkali‐Activated Coal Gangue Powder
Authors: Yang Yang , Yu Shengsheng , Ma Xiao , Hu Aiping , Li Ping
Published: May 2024

The aim of this study is to investigate the engineering properties and solidification mechanism of loess through the use of alkali‐activated coal gangue powder with sodium silicate. Experimental methods and comprehensive analysis were employed to examine the effects of different proportions of alkali‐activated coal gangue powder with sodium silicate on the engineering properties of loess, including mass shrinkage, compressibility, and shear strength. Additionally, scanning electron microscopy was utilized to gain in‐depth insights into the interaction and solidification mechanism between loess and alkali‐activated coal gangue powder. The results show that the sodium silicate alkali‐activated gangue powder curing loess has significantly improved the compressive strength and shear strength of the loess. With a ratio of 7 : 2 : 1, the 28 days compressive strength of solidified loess is 1.7 MPa, and the shear strength is 67.92 kPa, which is 1.91 and 2.13 times the 28 days compressive strength and shear strength of unmixed gangue powder and sodium silicate specimens respectively. The hydration–hydrolysis reaction, ion‐exchange reaction, and volcanic ash reaction of the gangue powder under an alkaline environment generated hydrides that filled the pores between soil particles, enhanced the interparticle cohesion, and made the internal structure of the specimens denser, improving the engineering performance of loess solidification. The proposed sodium silicate alkali‐activated gangue powder curing loess mechanism can provide a theoretical reference for the engineering application of gangue powder and the curing modification of loess.
Long‐Term Drying Shrinkage Strain of Engineered Cementitious Composite Concrete Contains Polymeric Fibers
Authors: Al-Mulla Ikram Faraoun , Al-Ameeri Abbas Salim , Al-Attar Tareq Salih
Published: May 2024

The lack of concrete tensile stress endurance led to the invention of engineered cementitious composite. However, the absence of gravel from the mixture in addition to the high binder content may lead to high shrinkage strain. Therefore, a radical solution to this problem is worth to be anticipated. The importance of this research lies in investigating the long‐term drying shrinkage strain of the engineered cementitious composite since there is a lack of information regarding this behavior. Mixes of 30 and 60 MPa strengths were produced with polyvinyl alcohol fibers PVA‐ECC and polypropylene fibers PP‐ECC. The drying shrinkage strain of PVA‐ECC mixes has been compared to PP‐ECC mixes for both short term (0–28 days) and long term (0–360 days). Results indicated that all PVA‐ECC mixes exhibited lower drying shrinkage strains than PP‐ECC mixes. The ultimate drying shrinkage strain was recorded to be 1200 microstrain at 28 days. The increment in drying shrinkage strain after 28 days was 5.6% in PVA‐ECC mixes when compared to that in PP‐ECC mixes which was 6.77%. For high strength levels, the drying shrinkage strain at the age of 360 days declared a reduction of 3.5% for PVA‐ECC compared to PP‐ECC mixes. Also, it was lower for mixes with 60 MPa (6.3%) than for mixes with 30 MPa (7.6%). Therefore, despite the higher cement content for mixes with 60 MPa strength, the higher fiber volume fraction and the higher PVA solution percentage restricted the drying shrinkage strain increment. The research also addresses some mechanical tests of engineered cementitious composite concrete such as compressive strength, flexural strength, and strain capacity that may provide a strong relation to the drying shrinkage behavior of the different mixes. The scanning electron microscope images were involved in this research to declare the impact of fiber types on the microstructure of the ECC mixes.
Figure S9 from Bile Acid Metabolism Mediates Cholesterol Homeostasis and Promotes Tumorigenesis in Clear Cell Renal Cell Carcinoma
Authors: Riscal Romain , Gardner Sarah M. , Coffey Nathan J. , Carens Madeleine , Mesaros Clementina , Xu Jimmy P. , Xue Yizheng , Davis Leah , Demczyszyn Sara , Vogt Austin , Olia Adam , Finan Jennifer M. , Godfrey Jason , Schultz David C. , Blair Ian A. , Keith Brian , Marmorstein Ronen , Skuli Nicolas , Simon M. Celeste
Published: May 2024

Figure S9
Figure S8 from Bile Acid Metabolism Mediates Cholesterol Homeostasis and Promotes Tumorigenesis in Clear Cell Renal Cell Carcinoma
Authors: Riscal Romain , Gardner Sarah M. , Coffey Nathan J. , Carens Madeleine , Mesaros Clementina , Xu Jimmy P. , Xue Yizheng , Davis Leah , Demczyszyn Sara , Vogt Austin , Olia Adam , Finan Jennifer M. , Godfrey Jason , Schultz David C. , Blair Ian A. , Keith Brian , Marmorstein Ronen , Skuli Nicolas , Simon M. Celeste
Published: May 2024

Figure S8
Supplementary Table from NPEPPS Is a Druggable Driver of Platinum Resistance
Authors: Jones Robert T. , Scholtes Mathijs , Goodspeed Andrew , Akbarzadeh Maryam , Mohapatra Saswat , Feldman Lily Elizabeth , Vekony Hedvig , Jean Annie , Tilton Charlene B. , Orman Michael V. , Romal Shahla , Deiter Cailin , Kan Tsung Wai , Xander Nathaniel , Araki Stephanie P. , Joshi Molishree , Javaid Mahmood , Clambey Eric T. , Layer Ryan , Laajala Teemu D. , Parker Sarah J. , Mahmoudi Tokameh , Zuiverloon Tahlita C.M. , Theodorescu Dan , Costello James C.
Published: May 2024

Supplementary Table 8
Supplementary Methods from DNA of Neutrophil Extracellular Traps Binds TMCO6 to Impair CD8+ T-cell Immunity in Hepatocellular Carcinoma
Authors: Song Mengjia , Zhang Chaoqi , Cheng Shaoyan , Ouyang Dijun , Ping Yu , Yang Jieying , Zhang YaoJun , Tang Yan , Chen Hao , Wang Qi-jing , Li Yong-qiang , He Jia , Xiang Tong , Zhang Yizhuo , Xia Jian-Chuan
Published: May 2024

Methods for Neutrophil isolation and culture, CD8+ T-cell isolation and culture, Tumor-infiltrating lymphocyte isolation, Cell membrane protein isolation, NET-DNA purification and biotin-labeling and so on.
Figure S6 from DNA of Neutrophil Extracellular Traps Binds TMCO6 to Impair CD8+ T-cell Immunity in Hepatocellular Carcinoma
Authors: Song Mengjia , Zhang Chaoqi , Cheng Shaoyan , Ouyang Dijun , Ping Yu , Yang Jieying , Zhang YaoJun , Tang Yan , Chen Hao , Wang Qi-jing , Li Yong-qiang , He Jia , Xiang Tong , Zhang Yizhuo , Xia Jian-Chuan
Published: May 2024

NET formation induced by TGF-β1 is blocked by inhibiting PAD4.
Supplementary Data from PABPC1L Induces IDO1 to Promote Tryptophan Metabolism and Immune Suppression in Renal Cell Carcinoma
Authors: Shu Guannan , Chen Minyu , Liao Wuyuan , Fu Liangmin , Lin Mingjie , Gui Chengpeng , Cen Junjie , Lu Jun , Chen Zhenhua , Wei Jinhuan , Chen Wei , Wang Yinghan , Zhu Jiangquan , Zhao Tianxin , Liu Xiaonan , Jing Jiajia , Liu Guo-chang , Pan Yihui , Luo Junhang , Zhang Jiaxing
Published: May 2024

Supporting information
Supplementary Data 1 from PABPC1L Induces IDO1 to Promote Tryptophan Metabolism and Immune Suppression in Renal Cell Carcinoma
Authors: Shu Guannan , Chen Minyu , Liao Wuyuan , Fu Liangmin , Lin Mingjie , Gui Chengpeng , Cen Junjie , Lu Jun , Chen Zhenhua , Wei Jinhuan , Chen Wei , Wang Yinghan , Zhu Jiangquan , Zhao Tianxin , Liu Xiaonan , Jing Jiajia , Liu Guo-chang , Pan Yihui , Luo Junhang , Zhang Jiaxing
Published: May 2024

Supplementary Data 1
Supplementary Table S5 from ATG-101 Is a Tetravalent PD-L1×4-1BB Bispecific Antibody That Stimulates Antitumor Immunity through PD-L1 Blockade and PD-L1–Directed 4-1BB Activation
Authors: Yuwen Hui , Wang Huajing , Li Tengteng , Ren Yijing , Zhang Yun-kai , Chen Peng , Sun Ao , Bian Gang , Li Bohua , Flowers David , Presler Marc , Subramanian Kalyanasundaram , Xue Jia , Wang Jingjing , Lynch Kevin , Mei Jay , He Xiaowen , Shan Bo , Hou Bing
Published: May 2024

Significant interactions between DC and T cells detected by Cellphone DB
Data from FUME-TCRseq Enables Sensitive and Accurate Sequencing of the T-cell Receptor from Limited Input of Degraded RNA
Authors: Baker Ann-Marie , Nageswaran Gayathri , Nenclares Pablo , Ronel Tahel , Smith Kane , Kimberley Christopher , Laclé Miangela M. , Bhide Shreerang , Harrington Kevin J. , Melcher Alan , Rodriguez-Justo Manuel , Chain Benny , Graham Trevor A.
Published: May 2024

Abstract
Genomic analysis of the T-cell receptor (TCR) reveals the strength, breadth, and clonal dynamics of the adaptive immune response to pathogens or cancer. The diversity of the TCR repertoire, however, means that sequencing is technically challenging, particularly for samples with low-quality, degraded nucleic acids. Here, we developed and validated FUME-TCRseq, a robust and sensitive RNA-based TCR sequencing methodology that is suitable for formalin-fixed paraffin-embedded samples and low amounts of input material. FUME-TCRseq incorporates unique molecular identifiers into each molecule of cDNA, allowing correction for sequencing errors and PCR bias. Using RNA extracted from colorectal and head and neck cancers to benchmark the accuracy and sensitivity of FUME-TCRseq against existing methods demonstrated excellent concordance between the datasets. Furthermore, FUME-TCRseq detected more clonotypes than a commercial RNA-based alternative, with shorter library preparation time and significantly lower cost. The high sensitivity and the ability to sequence RNA of poor quality and limited amount enabled quantitative analysis of small numbers of cells from archival tissue sections, which is not possible with other methods. Spatially resolved FUME-TCRseq analysis of colorectal cancers using macrodissected archival samples revealed the shifting T-cell landscapes at the transition to an invasive phenotype and between tumor subclones containing distinct driver alterations. In summary, FUME-TCRseq represents an accurate, sensitive, and low-cost tool for the characterization of T-cell repertoires, particularly in samples with low-quality RNA that have not been accessible using existing methodology.
Significance:
FUME-TCRseq is a TCR sequencing methodology that supports sensitive and spatially resolved detection of TCR clones in archival clinical specimens, which can facilitate longitudinal tracking of immune responses through disease course and treatment.
Data from Lipid-Encapsulated mRNAs Encoding Complex Fusion Proteins Potentiate Antitumor Immune Responses
Authors: Shuptrine Casey W. , Chen Yuhui , Miriyala Jayalakshmi , Lenz Karen , Moffett Danielle , Nguyen Thuy-Ai , Michaux Jenn , Campbell Kristen , Smith Connor , Morra Marc , Rivera-Molina Yisel , Murr Noah , Cooper Sarah , McGuire Ashlyn , Makani Vishruti , Oien Nathan , Zugates Jeffery T. , de Silva Suresh , Schreiber Taylor H. , de Picciotto Seymour , Fromm George
Published: May 2024

Abstract
Lipid nanoparticle (LNP)–encapsulated mRNA has been used for in vivo production of several secreted protein classes, such as IgG, and has enabled the development of personalized vaccines in oncology. Establishing the feasibility of delivering complex multispecific modalities that require higher-order structures important for their function could help expand the use of mRNA/LNP biologic formulations. Here, we evaluated whether in vivo administration of mRNA/LNP formulations of SIRPα-Fc-CD40L and TIGIT-Fc-LIGHT could achieve oligomerization and extend exposure, on-target activity, and antitumor responses comparable with that of the corresponding recombinant fusion proteins. Intravenous infusion of the formulated LNP-encapsulated mRNAs led to rapid and sustained production of functional hexameric proteins in vivo, which increased the overall exposure relative to the recombinant protein controls by ∼28 to 140 fold over 96 hours. High concentrations of the mRNA-encoded proteins were also observed in secondary lymphoid organs and within implanted tumors, with protein concentrations in tumors up to 134-fold greater than with the recombinant protein controls 24 hours after treatment. In addition, SIRPα-Fc-CD40L and TIGIT-Fc-LIGHT mRNAs induced a greater increase in antigen-specific CD8+ T cells in the tumors. These mRNA/LNP formulations were well tolerated and led to a rapid increase in serum and intratumoral IL2, delayed tumor growth, extended survival, and outperformed the activities of benchmark mAb controls. Furthermore, the mRNA/LNPs demonstrated improved efficacy in combination with anti-PD-L1 relative to the recombinant fusion proteins. These data support the delivery of complex oligomeric biologics as mRNA/LNP formulations, where high therapeutic expression and exposure could translate into improved patient outcomes.
Significance:
Lipid nanoparticle–encapsulated mRNA can efficiently encode complex fusion proteins encompassing immune checkpoint blockers and costimulators that functionally oligomerize in vivo with extended pharmacokinetics and durable exposure to induce potent antitumor immunity.
AACR Cancer Disparities Progress Report 2024: Achieving the Bold Vision of Health Equity
Authors: Williams Patrick A. , Zaidi Sayyed K. , Ramian Haleh , Sengupta Rajarshi
Published: May 2024

Advances in cancer prevention, early detection, and treatments have led to unprecedented progress against cancer. However, these advances have not benefited everyone equally. Because of a long history of structural inequities and systemic injustices in the United States, many segments of the US population continue to shoulder a disproportionate burden of cancer. The American Association for Cancer Research (AACR) Cancer Disparities Progress Report 2024 (CancerDisparitiesProgressReport.org) outlines the recent progress against cancer disparities, the ongoing challenges faced by medically underserved populations, and emphasizes the vital need for further advances in cancer research and patient care to benefit all populations.
Star Table 1 from Targeting CCL2/CCR2 Signaling Overcomes MEK Inhibitor Resistance in Acute Myeloid Leukemia
Authors: Modak Rucha V. , de Oliveira Rebola Katia G. , McClatchy John , Mohammadhosseini Mona , Damnernsawad Alisa , Kurtz Stephen E. , Eide Christopher A. , Wu Guanming , Laderas Ted , Nechiporuk Tamilla , Gritsenko Marina A. , Hansen Joshua R. , Hutchinson Chelsea , Gosline Sara J.C. , Piehowski Paul , Bottomly Daniel , Short Nicholas , Rodland Karin , McWeeney Shannon K. , Tyner Jeffrey W. , Agarwal Anupriya
Published: May 2024

Resource Table
Supplementary Table S1 from Targeting SMAD3 Improves Response to Oxaliplatin in Esophageal Adenocarcinoma Models by Impeding DNA Repair
Authors: Ballout Farah , Lu Heng , Bhat Nadeem , Chen Lei , Peng Dunfa , Chen Zheng , Chen Steven , Sun Xiaodian , Giordano Silvia , Corso Simona , Zaika Alexander , McDonald Oliver , Livingstone Alan S. , El-Rifai Wael
Published: May 2024

Supplementary key resources table 1. Antibodies source and dilution
Supplementary Table S1 from Response Rate and Molecular Correlates to Encorafenib and Binimetinib in BRAF-V600E Mutant High-Grade Glioma
Authors: Schreck Karisa C. , Strowd Roy E. , Nabors Louis B. , Ellingson Benjamin M. , Chang Michael , Tan Sze K. , Abdullaev Zied , Turakulov Rust , Aldape Kenneth , Danda Neeraja , Desideri Serena , Fisher Joy , Iacoboni Michaella , Surakus Trisha , Rudek Michelle A. , Bettegowda Chetan , Grossman Stuart A. , Ye Xiaobu
Published: May 2024

Supplementary Table S1: Representativeness of study participants.
Supplementary Table S5 from FDA Approval Summary: Enfortumab Vedotin plus Pembrolizumab for Cisplatin-Ineligible Locally Advanced or Metastatic Urothelial Carcinoma
Authors: Maguire William F. , Lee Daniel , Weinstock Chana , Gao Xin , Bulik Catharine C. , Agrawal Sundeep , Chang Elaine , Hamed Salaheldin S. , Bloomquist Erik W. , Tang Shenghui , Pazdur Richard , Kluetz Paul G. , Amiri-Kordestani Laleh , Suzman Daniel L.
Published: May 2024

Table S5 shows the percentage of patients with resolution of neuropathy at last assessment of neuropathy in EV-103 and EV monotherapy pooled data
Supplementary Table S3 from FDA Approval Summary: Enfortumab Vedotin plus Pembrolizumab for Cisplatin-Ineligible Locally Advanced or Metastatic Urothelial Carcinoma
Authors: Maguire William F. , Lee Daniel , Weinstock Chana , Gao Xin , Bulik Catharine C. , Agrawal Sundeep , Chang Elaine , Hamed Salaheldin S. , Bloomquist Erik W. , Tang Shenghui , Pazdur Richard , Kluetz Paul G. , Amiri-Kordestani Laleh , Suzman Daniel L.
Published: May 2024

Table S3 shows incidence of new peripheral neuropathy over time in patients receiving combination treatment in EV-103
Supplementary Table S2 from A Phase II Open-Label Randomized Clinical Trial of Preoperative Durvalumab or Durvalumab plus Tremelimumab in Resectable Head and Neck Squamous Cell Carcinoma
Authors: Kim Chang Gon , Hong Min Hee , Kim Dahee , Lee Brian Hyohyoung , Kim Hyunwook , Ock Chan-Young , Kelly Geoffrey , Bang Yoon Ji , Kim Gamin , Lee Jung Eun , Kim Chaeyeon , Kim Se-Heon , Hong Hyun Jun , Park Young Min , Sim Nam Suk , Park Heejung , Park Jin Woo , Lee Chang Geol , Kim Kyung Hwan , Park Goeun , Jung Inkyung , Han Dawoon , Kim Jong Hoon , Cha Junha , Lee Insuk , Kang Mingu , Song Heon , Oum Chiyoon , Kim Seulki , Kim Sukjun , Lim Yoojoo , Kim-Schulze Seunghee , Merad Miriam , Yoon Sun Och , Kim Hyun Je , Koh Yoon Woo , Kim Hye Ryun
Published: May 2024

Representativeness of study participants.
Supplementary Figure S2 from A Phase II Open-Label Randomized Clinical Trial of Preoperative Durvalumab or Durvalumab plus Tremelimumab in Resectable Head and Neck Squamous Cell Carcinoma
Authors: Kim Chang Gon , Hong Min Hee , Kim Dahee , Lee Brian Hyohyoung , Kim Hyunwook , Ock Chan-Young , Kelly Geoffrey , Bang Yoon Ji , Kim Gamin , Lee Jung Eun , Kim Chaeyeon , Kim Se-Heon , Hong Hyun Jun , Park Young Min , Sim Nam Suk , Park Heejung , Park Jin Woo , Lee Chang Geol , Kim Kyung Hwan , Park Goeun , Jung Inkyung , Han Dawoon , Kim Jong Hoon , Cha Junha , Lee Insuk , Kang Mingu , Song Heon , Oum Chiyoon , Kim Seulki , Kim Sukjun , Lim Yoojoo , Kim-Schulze Seunghee , Merad Miriam , Yoon Sun Och , Kim Hyun Je , Koh Yoon Woo , Kim Hye Ryun
Published: May 2024

Expression of T cell markers according to immune phenotypes based on artificial intelligence-powered analysis using the Cancer Genome Atlas Head-Neck Squamous Cell Carcinoma cohort.
Supplementary Table S6 from Biomarkers of Efficacy and Safety of the Academic BCMA-CART ARI0002h for the Treatment of Refractory Multiple Myeloma
Authors: Oliver-Caldes Aina , Español-Rego Marta , Zabaleta Aintzane , González-Calle Verónica , Navarro-Velázquez Sergio , Inogés Susana , de Cerio Ascensión López-Díaz , Cabañas Valentín , López-Muñoz Nieves , Rodríguez-Otero Paula , Reguera Juan Luis , Moreno David F. , Martínez-Cibrian Nuria , López-Corral Lucía , Pérez-Amill Lorena , Martin-Antonio Beatriz , Rosiñol Laura , Cid Joan , Tovar Natalia , Sáez-Peñataro Joaquín , López-Parra Miriam , Olesti Eulalia , Guillén Elena , Varea Sara , Rodríguez-Lobato Luis Gerardo , Battram Anthony M. , González Marta Sonia , Sánchez-Salinas Andrés , González-Navarro Azucena , Ortiz-Maldonado Valentín , Delgado Julio , Prósper Felipe , Juan Manel , Martínez-López Joaquín , Moraleda José M. , Mateos Maria Victoria , Urbano-Ispizua Álvaro , Paiva Bruno , Pascal Mariona , Fernández de Larrea Carlos
Published: May 2024

Table 6. Detection of CART antibodies at different timepoints.
Supplementary Figure S16 from A Phase II Open-Label Randomized Clinical Trial of Preoperative Durvalumab or Durvalumab plus Tremelimumab in Resectable Head and Neck Squamous Cell Carcinoma
Authors: Kim Chang Gon , Hong Min Hee , Kim Dahee , Lee Brian Hyohyoung , Kim Hyunwook , Ock Chan-Young , Kelly Geoffrey , Bang Yoon Ji , Kim Gamin , Lee Jung Eun , Kim Chaeyeon , Kim Se-Heon , Hong Hyun Jun , Park Young Min , Sim Nam Suk , Park Heejung , Park Jin Woo , Lee Chang Geol , Kim Kyung Hwan , Park Goeun , Jung Inkyung , Han Dawoon , Kim Jong Hoon , Cha Junha , Lee Insuk , Kang Mingu , Song Heon , Oum Chiyoon , Kim Seulki , Kim Sukjun , Lim Yoojoo , Kim-Schulze Seunghee , Merad Miriam , Yoon Sun Och , Kim Hyun Je , Koh Yoon Woo , Kim Hye Ryun
Published: May 2024

High-dimensional profiling of non-regulatory CD4+ T cells.
Supplementary Figure S1 from Circulating microRNA Analysis in a Prospective Co-clinical Trial Identifies MIR652–3p as a Response Biomarker and Driver of Regorafenib Resistance Mechanisms in Colorectal Cancer
Authors: Hedayat Somaieh , Cascione Luciano , Cunningham David , Schirripa Marta , Lampis Andrea , Hahne Jens C. , Tunariu Nina , Hong Sung Pil , Marchetti Silvia , Khan Khurum , Fontana Elisa , Angerilli Valentina , Delrieux Mia , Nava Rodrigues Daniel , Procaccio Letizia , Rao Sheela , Watkins David , Starling Naureen , Chau Ian , Braconi Chiara , Fotiadis Nicos , Begum Ruwaida , Guppy Naomy , Howell Louise , Valenti Melanie , Cribbes Scott , Kolozsvari Bernadett , Kirkin Vladimir , Lonardi Sara , Ghidini Michele , Passalacqua Rodolfo , Elghadi Raghad , Magnani Luca , Pinato David J. , Di Maggio Federica , Ghelardi Filippo , Sottotetti Elisa , Vetere Guglielmo , Ciracì Paolo , Vlachogiannis Georgios , Pietrantonio Filippo , Cremolini Chiara , Cortellini Alessio , Loupakis Fotios , Fassan Matteo , Valeri Nicola
Published: May 2024

Supplementary Figure S1. Bio-speciment collection, MIR652-3p expression and clinical correlates in the PROSPECT-R and validation cohorts
Supplementary S1-S8 from Ataxia-Telangiectasia Mutated Loss-of-Function Displays Variant and Tissue-Specific Differences across Tumor Types
Authors: Pilié Patrick G. , Giuliani Virginia , Wang Wei-Lien , McGrail Daniel J. , Bristow Christopher A. , Ngoi Natalie Y.L. , Kyewalabye Keith , Wani Khalida M. , Le Hung , Campbell Erick , Sanchez Nora S. , Yang Dong , Gheeya Jinesh S. , Goswamy Rohit Vivek , Holla Vijaykumar , Shaw Kenna Rael , Meric-Bernstam Funda , Liu Chiu-Yi , Ma XiaoYan , Feng Ningping , Machado Annette A. , Bardenhagen Jennifer P. , Vellano Christopher P. , Marszalek Joseph R. , Rajendra Eeson , Piscitello Desiree , Johnson Timothy I. , Likhatcheva Maria , Elinati Elias , Majithiya Jayesh , Neves Joana , Grinkevich Vera , Ranzani Marco , Luzarraga Marina Roy , Boursier Marie , Armstrong Lucy , Geo Lerin , Lillo Giorgia , Tse Wai Yiu , Lazar Alexander J. , Kopetz Scott E. , Geck Do Mary K. , Lively Sarah , Johnson Michael G. , Robinson Helen M.R. , Smith Graeme C.M. , Carroll Christopher L. , Di Francesco M. Emilia , Jones Philip , Heffernan Timothy P. , Yap Timothy A.
Published: May 2024

supplementary figures
Data from Biomarkers of Efficacy and Safety of the Academic BCMA-CART ARI0002h for the Treatment of Refractory Multiple Myeloma
Authors: Oliver-Caldes Aina , Español-Rego Marta , Zabaleta Aintzane , González-Calle Verónica , Navarro-Velázquez Sergio , Inogés Susana , de Cerio Ascensión López-Díaz , Cabañas Valentín , López-Muñoz Nieves , Rodríguez-Otero Paula , Reguera Juan Luis , Moreno David F. , Martínez-Cibrian Nuria , López-Corral Lucía , Pérez-Amill Lorena , Martin-Antonio Beatriz , Rosiñol Laura , Cid Joan , Tovar Natalia , Sáez-Peñataro Joaquín , López-Parra Miriam , Olesti Eulalia , Guillén Elena , Varea Sara , Rodríguez-Lobato Luis Gerardo , Battram Anthony M. , González Marta Sonia , Sánchez-Salinas Andrés , González-Navarro Azucena , Ortiz-Maldonado Valentín , Delgado Julio , Prósper Felipe , Juan Manel , Martínez-López Joaquín , Moraleda José M. , Mateos Maria Victoria , Urbano-Ispizua Álvaro , Paiva Bruno , Pascal Mariona , Fernández de Larrea Carlos
Published: May 2024

AbstractPurpose:
B-cell maturation antigen (BCMA)-chimeric antigen receptor T-cells (CART) improve results obtained with conventional therapy in the treatment of relapsed/refractory multiple myeloma. However, the high demand and expensive costs associated with CART therapy might prove unsustainable for health systems. Academic CARTs could potentially overcome these issues. Moreover, response biomarkers and resistance mechanisms need to be identified and addressed to improve efficacy and patient selection. Here, we present clinical and ancillary results of the 60 patients treated with the academic BCMA-CART, ARI0002h, in the CARTBCMA-HCB-01 trial.
Patients and Methods:
We collected apheresis, final product, peripheral blood and bone marrow samples before and after infusion. We assessed BCMA, T-cell subsets, CART kinetics and antibodies, B-cell aplasia, cytokines, and measurable residual disease by next-generation flow cytometry, and correlated these to clinical outcomes.
Results:
At cut-off date March 17, 2023, with a median follow-up of 23.1 months (95% CI, 9.2–37.1), overall response rate in the first 3 months was 95% [95% confidence interval (CI), 89.5–100]; cytokine release syndrome (CRS) was observed in 90% of patients (5% grades ≥3) and grade 1 immune effector cell-associated neurotoxicity syndrome was reported in 2 patients (3%). Median progression-free survival was 15.8 months (95% CI, 11.5–22.4). Surface BCMA was not predictive of response or survival, but soluble BCMA correlated with worse clinical outcomes and CRS severity. Activation marker HLA-DR in the apheresis was associated with longer progression-free survival and increased exhaustion markers correlated with poorer outcomes. ARI0002h kinetics and loss of B-cell aplasia were not predictive of relapse.
Conclusions:
Despite deep and sustained responses achieved with ARI0002h, we identified several biomarkers that correlate with poor outcomes.
HDAC6 Inhibition Releases HR23B to Activate Proteasomes, Expand the Tumor Immunopeptidome and Amplify T-cell Antimyeloma Activity
Authors: Rana Priyanka S. , Ignatz-Hoover James J. , Kim Byung-Gyu , Malek Ehsan , Federov Yuriy , Adams Drew , Chan Timothy , Driscoll James J.
Published: May 2024

Proteasomes degrade intracellular proteins to generate antigenic peptides that are recognized by the adaptive immune system and promote anticancer immunity. However, tumors subvert the antigen presentation machinery to escape immunosurveillance. We hypothesized that proteasome activation could concomitantly increase antigen abundance and diversity in multiple myeloma cells. High-throughput screens revealed that histone deacetylase 6 (HDAC6) inhibitors activated proteasomes to unmask neoantigens and amplify the tumor-specific antigenic landscape. Treatment of patient CD138+ cells with HDAC6 inhibitors significantly promoted the antimyeloma activity of autologous CD8+ T cells. Pharmacologic blockade and genetic ablation of the HDAC6 ubiquitin-binding domain released HR23B, which shuttles ubiquitinylated cargo to proteasomes, while silencing HDAC6 or HR23B in multiple myeloma cells abolished the effect of HDAC6 inhibitors on proteasomes, antigen presentation, and T-cell cytotoxicity. Taken together, our results demonstrate the paradigm-shifting translational impact of proteasome activators to expand the myeloma immunopeptidome and have revealed novel, actionable antigenic targets for T cell–directed immunotherapy.

Significance:

The elimination of therapy-resistant tumor cells remains a major challenge in the treatment of multiple myeloma. Our study identifies and functionally validates agents that amplify MHC class I–presented antigens and pave the way for the development of proteasome activators as immune adjuvants to enhance immunotherapeutic responses in patients with multiple myeloma.
Developmental Causes of Focal Segmental Glomerulosclerosis
Authors: Shane Klomp Luna , Levtchenko Elena , Westland Rik
Published: May 2024

Background: Focal segmental glomerulosclerosis (FSGS) is a histological pattern of glomerular damage that includes idiopathic conditions as well as genetic and non-genetic forms. Among these various etiologies, different phenotypes within the spectrum of congenital anomalies of the kidney and urinary tract (CAKUT) have been associated with FSGS. Summary: Until recently, the main pathomechanism of how congenital kidney and urinary tract defects lead to FSGS was attributed to a reduced number of nephrons, resulting in biomechanical stress on the remaining glomeruli, detachment of podocytes, and subsequent inability to maintain normal glomerular architecture. The discovery of deleterious single-nucleotide variants in PAX2, a transcription factor crucial in normal kidney development and a known cause of papillorenal syndrome, in individuals with adult-onset FSGS without congenital kidney defects has shed new light on developmental defects that become evident during podocyte injury. Key Message: In this mini-review, we challenge the assumption that FSGS in CAKUT is caused by glomerular hyperfiltration alone and hypothesize a multifactorial pathogenesis that includes overlapping cellular mechanisms that are activated in both damaged podocytes as well as nephron progenitor cells.
Majie Cataplasm Alleviates Asthma by Regulating Th1/Th2/Treg/Th17 Balance
Authors: Liu Yuanjun , Liu Haixia , Shao Qi , Shi Hanfen , Cheng Fafeng , Wang Xueqian
Published: May 2024

Introduction: T cells play a critical role in inflammatory diseases. The aim of the present study was to investigate the effects of Majie cataplasm (MJC) on asthma and to propose a possible mechanism involved in this process. Methods: Airway inflammation, infiltration of inflammatory cells, levels of interleukin (IL)-4, IL-10, IL-17, and interferon (IFN)-γ, levels of Th2, Treg, Th17, and Th1 cells, and the expressions of IL-4, IL-10, IL-17, IFN-γ, GATA binding protein 3 (GATA-3), Foxp3, RAR-related orphan receptor gamma (RORγt), and T-bet were detected. Result: MJC treatment reduced lung airway resistance and inflammatory infiltration in lung tissues. MJC treatment also reduced the numbers of eosinophils and neutrophils in the blood and bronchoalveolar lavage fluid (BALF). The levels of IL-4 and IL-17 in the blood, BALF, and lungs were suppressed by MJC, and IFN-γ and IL-10 were increased. Furthermore, MJC suppressed the percentage of Th2 and Th17 and increased the percentage of Th1 and Treg in spleen cells. In addition, MJC can inhibit asthma by increasing expressions of IFN-γ, IL-10, T-bet, and Foxp3, as well as decreasing expressions of IL-4, IL-17, GATA-3, and RORγt. Conclusion: MJC may improve airway hyperresponsiveness and inflammation by regulating Th1/Th2/Treg/Th17 balance in ovalbumin-induced rats. And MJC may be a new source of anti-asthma drugs.
Association between Mitral Valve Mean Pressure Gradient and Atrial Fibrillation in Patients with Rheumatic Mitral Stenosis: A Cross-Sectional Study
Authors: Wu Changcai
Published: May 2024

Introduction: Atrial fibrillation (AF) often occurs in patients with rheumatic mitral stenosis (RMS) and is associated with adverse clinical outcomes. Mitral valve mean pressure gradient (MVMPG) is utilized as an indicator to assess the severity of mitral stenosis and its hemodynamic implications. The aim of this study was to investigate the association between MVMPG and AF in individuals with RMS. Methods: We conducted a retrospective analysis of medical records from 360 consecutive patients diagnosed with RMS at the First Affiliated Hospital of Wenzhou Medical University between January 2018 and January 2023. Using both univariate and multivariate logistic regression models, the relationship between MVMPG and AF was evaluated. Restricted cubic splines were employed to test for linearity, and stratified and interaction analyses were performed to evaluate the stability of this relationship among different subgroups. Results: Based on the MVMPG levels, 360 RMS patients in total were categorized into three groups for the analysis: Q1 (<5 mm Hg), Q2 (5–10 mm Hg), and Q3 (>10 mm Hg). The average age was 60.6 years (Q1: 66.1, Q2: 61.9, Q3: 55.8), and 70.8% were female. The prevalence of AF was 39.6%, 56.5%, and 63.2% in Q1, Q2, and Q3, respectively. After adjusting for potential confounders, a significant association between MVMPG and AF was observed. In Q2, there was a 119% increase in AF (OR 2.19, 95% CI: 1.01–4.75), while in Q3, there was a 238% increase (OR 3.38, 95% CI: 1.39–8.19), compared to Q1. The relationship between MVMPG and AF was linear (p = 0.503). These results remained consistent in each subgroup analysis. Conclusion: Our study reveals a significant positive association between MVMPG and AF in patients with RMS, which holds important clinical implications. It is necessary to conduct further research.
MICU3 Regulates Mitochondrial Calcium and Cardiac Hypertrophy
Authors: Roman Barbara , Mastoor Yusuf , Sun Junhui , Chapoy Villanueva Hector , Hinojosa Gabriela , Springer Danielle , Liu Julia C. , Murphy Elizabeth
Published: May 2024

BACKGROUND:

Calcium (Ca
2+
) uptake by mitochondria occurs via the mitochondrial Ca
2+
uniporter. Mitochondrial Ca
2+
uniporter exists as a complex, regulated by 3 MICU (mitochondrial Ca
2+
uptake) proteins localized in the intermembrane space: MICU1, MICU2, and MICU3. Although MICU3 is present in the heart, its role is largely unknown.

METHODS:

We used CRISPR-Cas9 to generate a mouse with global deletion of MICU3 and an adeno-associated virus (AAV9) to overexpress MICU3 in wild-type mice. We examined the role of MICU3 in regulating mitochondrial calcium ([Ca
2+
]
m
) in ex vivo hearts using an optical method following adrenergic stimulation in perfused hearts loaded with a Ca
2+
-sensitive fluorophore. Additionally, we studied how deletion and overexpression of MICU3, respectively, impact cardiac function in vivo by echocardiography and the molecular composition of the mitochondrial Ca
2+
uniporter complex via Western blot, immunoprecipitation, and Blue native-PAGE analysis. Finally, we measured MICU3 expression in failing human hearts.

RESULTS:

MICU3 knock out hearts and cardiomyocytes exhibited a significantly smaller increase in [Ca
2+
]
m
than wild-type hearts following acute isoproterenol infusion. In contrast, heart with overexpression of MICU3 exhibited an enhanced increase in [Ca
2+
]
m
compared with control hearts. Echocardiography analysis showed no significant difference in cardiac function in knock out MICU3 mice relative to wild-type mice at baseline. However, mice with overexpression of MICU3 exhibited significantly reduced ejection fraction and fractional shortening compared with control mice. We observed a significant increase in the ratio of heart weight to tibia length in hearts with overexpression of MICU3 compared with controls, consistent with hypertrophy. We also found a significant decrease in MICU3 protein and expression in failing human hearts.

CONCLUSIONS:

Our results indicate that increased and decreased expression of MICU3 enhances and reduces, respectively, the uptake of [Ca
2+
]
m
in the heart. We conclude that MICU3 plays an important role in regulating [Ca
2+
]
m
physiologically, and overexpression of MICU3 is sufficient to induce cardiac hypertrophy, making MICU3 a possible therapeutic target.
o
8
G Site-Specifically Modified tRF-1-AspGTC: A Novel Therapeutic Target and Biomarker for Pulmonary Hypertension
Authors: Zhang Junting , Li Yiying , Chen Yuan , Zhang Jianchao , Jia Zihui , He Muhua , Liao Xueyi , He Siyu , Bian Jin-Song , Nie Xiao-Wei
Published: May 2024

BACKGROUND:

Hypoxia and oxidative stress contribute to the development of pulmonary hypertension (PH). tRNA-derived fragments play important roles in RNA interference and cell proliferation, but their epitranscriptional roles in PH development have not been investigated. We aimed to gain insight into the mechanistic contribution of oxidative stress–induced 8-oxoguanine in pulmonary vascular remodeling.

METHODS:

Through small RNA modification array analysis and quantitative polymerase chain reaction, a significant upregulation of the 8-oxoguanine -modified tRF-1-AspGTC was found in the lung tissues and the serum of patients with PH.

RESULTS:

This modification occurs at the position 5 of the tRF-1-AspGTC (5o
8
G tRF). Inhibition of the 5o
8
G tRF reversed hypoxia-induced proliferation and apoptosis resistance in pulmonary artery smooth muscle cells. Further investigation unveiled that the 5o
8
G tRF retargeted mRNA of WNT5A (Wingless-type MMTV integration site family, member 5A) and CASP3 (Caspase3) and inhibited their expression. Ultimately, BMPR2 (Bone morphogenetic protein receptor 2) -reactive oxygen species/5o
8
G tRF/WNT5A signaling pathway exacerbated the progression of PH.

CONCLUSIONS:

Our study highlights the role of site-specific 8-oxoguanine–modified tRF in promoting the development of PH. Our findings present a promising therapeutic avenue for managing PH and propose 5o
8
G tRF as a potential innovative marker for diagnosing this disease.
Does Online Testing Make the Grade? Evidence from a Randomized Controlled Trial
Authors: Atwater Ann , Rush Mark , Saygin Perihan
Published: May 2024

As a result of the increase in online course offerings at colleges and universities, the prevalence of online and computerized examinations has increased over the last two decades. Beyond academia, online examinations have been used to assess competence for certifications by both governments and private firms. Despite this importance, a randomized controlled trial that randomizes individual test takers into online and in-person examinations has not previously been conducted. In this paper, we rectify this by conducting this experiment in a large economics class at a large research university in the American southeast. We supplement our experiment results with a novel methodology of using screening surveys administered to potential volunteers which solicit preference information. We find that online testing reduces examination grades by over a tenth of a standard deviation, relative to in-person assessment. Additional exploratory exercises provide evidence that this effect is driven by students who prefer in-person examinations.
A new species of Polystemma (Apocynaceae, Asclepiadoideae, Asclepiadeae, Gonolobineae) from the state of Oaxaca, Mexico
Authors: ALVARADO-CÁRDENAS LEONARDO O. , GARCÍA-MENDOZA ABISAÍ JOSUÉ , SANDOVAL-GUTIÉRREZ DANIEL , LOZADA-PÉREZ LUCIO
Published: May 2024

We describe a new species of Polystemma endemic to Oaxaca, Mexico. Polystemma leopardum is similar to P. cordatum but differs in the shape of the corolla lobes, flower color pattern, shape of the gynostegial corona and stylar head, as well as its specialized habitat. We describe and discuss its morphology and provide illustrations and a distribution map. We propose its conservation status as Endangered under the criteria of the IUCN. This discovery increases the diversity of the genus in the country to ten species.
Diospyros adinandrifolia, a new species of Ebenaceae from Yunnan, China
Authors: LIU QUN , ZOU CHUN-YU , YANG CHONG , CHEN WEN-HONG , LYU LING , ZHANG GUI-LIANG , SHUI YU-MIN , ZHANG ZHI-XIANG
Published: May 2024

Diospyros adinandrifolia, a new species of Diospyros (Ebenaceae) from southeast Yunnan, China, is described and photographed. Photographs of type specimens and ecological information are provided. Diospyros adinandrifolia resembles D. undulata in its elliptic leaves, clustered flowers, and synsepalous calyces, but differs by abaxial leaf base without glands, calyx without obvious lobes and the fruiting calyx being not reflexed during maturation. It is also morphologically similar to D. dussaudii in buds shape and inflorescence morphology, but differs in its leaves being white pubescent when young and glabrescent, paniculate male inflorescences, and succulent fruit. Based on the examination of the specimens from China and Vietnam, the species is categorized as Endangered (EN) according to the IUCN Red List criteria.
Maintenance of the Zonal Momentum Balance of the Antarctic Circumpolar Current by Barotropic Dynamics
Authors: Zhang Xihan , Nikurashin Maxim , Peña-Molino Beatriz , Rintoul Stephen R. , Doddridge Edward
Published: May 2024

The vertically integrated zonal momentum balance of the Antarctic Circumpolar Current (ACC) is dominated by wind stress at the surface and topographic form stress (TFS) at the bottom. It has been argued that wind stress is transferred from the surface to the bottom by transient baroclinic eddies, via interfacial form stress, to establish the balance between wind stress and TFS. However, ocean models indicate TFS responds rapidly to changes in wind stress, suggesting that barotropic processes play a role in this balance. We investigate the dynamics governing the wind–TFS balance of the ACC and its response to wind using an idealized, wind- and buoyancy-driven channel model. We show that the balance is established and maintained at equilibrium by the barotropic dynamics. The balance results from the continuity of the flow, in which the Ekman transport at the surface, balanced by wind stress, is compensated by a return flow at depth, balanced by TFS. This leads to a match between wind stress and TFS which is independent of momentum stresses in the interior. Transient baroclinic eddies oppose the wind-driven isopycnal steepening via eddy buoyancy fluxes, which act to flatten the isopycnals. The eddy-driven isopycnal flattening corresponds to a reduction in the zonal geostrophic shear and thus a redistribution of the zonal momentum in the interior via eddy momentum stresses. The maintenance of the vertically integrated ACC momentum balance by the barotropic dynamics explains the fast response of the wind–TFS balance to changes in wind forcing.