bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of a putative cell wall-hydrolyzing amidase involved in sporangiospore maturation in
Actinoplanes missouriensis
Authors: Tan Zhuwen , Tezuka Takeaki , Ohnishi Yasuo
Published: March 2024

Actinoplanes missouriensis
is a filamentous bacterium that differentiates into terminal sporangia, each containing a few hundred spores. Previously, we reported that a cell wall-hydrolyzing
N
-acetylglucosaminidase, GsmA, is required for the maturation process of sporangiospores in
A. missouriensis
; sporangia of the
gsmA
null mutant (Δ
gsmA
) strain released chains of 2–20 spores under sporangium dehiscence-inducing conditions. In this study, we identified and characterized a putative cell wall hydrolase (AsmA) that is also involved in sporangiospore maturation. AsmA was predicted to have a signal peptide for the general secretion pathway and an
N
-acetylmuramoyl-
l
-alanine amidase domain. The transcript level of
asmA
increased during the early stages of sporangium formation. The
asmA
null mutant (Δ
asmA
) strain showed phenotypes similar to those of the wild-type strain, but sporangia of the Δ
gsmA
Δ
asmA
double mutant released longer spore chains than those from the Δ
gsmA
sporangia. Furthermore, a weak interaction between AsmA and GsmA was detected in a bacterial two-hybrid assay using
Escherichia coli
as the host. Based on these results, we propose that AsmA is an enzyme that hydrolyzes peptidoglycan at septum-forming sites to separate adjacent spores during sporangiospore maturation in cooperation with GsmA in
A. missouriensis
.

IMPORTANCE

Actinoplanes missouriensis
produces sporangiospores as dormant cells. The spores inside the sporangia are assumed to be formed from prespores generated by the compartmentalization of intrasporangium hyphae via septation. Previously, we identified GsmA as a cell wall hydrolase responsible for the separation of adjacent spores inside sporangia. However, we predicted that an additional cell wall hydrolase(s) is inevitably involved in the maturation process of sporangiospores because the sporangia of the
gsmA
null mutant strain released not only tandemly connected spore chains (2–20 spores) but also single spores. In this study, we successfully identified a putative cell wall hydrolase (AsmA) that is involved in sporangiospore maturation in
A. missouriensis
.
Performance of eight commercial immunoassays for the detection of cytomegalovirus-specific IgM antibodies in pregnancy – no test fits all needs
Authors: Daiminger Anja , Beck Robert , Exler Simone , Bartelt Uwe , Enders Martin
Published: March 2024

Detection of cytomegalovirus (CMV)-specific immunoglobulin M (IgM) antibodies as first-line serologic diagnosis plays an important role in identifying CMV primary infection during pregnancy. The performance characteristics of eight commercially available CMV IgM assays were compared. Sensitivity and IgM antibody kinetics were assessed using 100 acute phase and follow-up sera from 39 pregnant women with a well-defined onset of CMV primary infection. Specificity was analyzed using 50 well-characterized serum samples from pregnant women not infected or latently infected with CMV and from patients with other acute infections. Until 12 weeks after the onset of primary infection, four assays showed sensitivities of 100%, whereas the others had individual gaps to detect all primary infections in this time period. All assays showed a time-dependent decrease of IgM levels. More than 12 weeks after the onset of infection, the IgM-positive rates varied considerably between tests. The specificity was between 92% and 98% in all but one assay. The observed differences in the performance characteristics must be taken into account in CMV screening and diagnosis of primary infection during pregnancy.
Supplemental Material: Intra-arc rifting induced the fragmentation of microplate from the continental margin
Authors: Wu Limin , Peng Touping , et al.
Published: March 2024

Figure S1: Chondrite-normalized rare earth elemental data for the zircons analyzed from the Diancangshan Massif. Figure S2: Plot of samples Y, Zr, Hf, and Ti versus loss on ignition in the Diancangshan Massif. Figure S3: Plot of samples Th, Ta, Nb, and rare earth element versus Zr in the Diancangshan Massif. Table S1: Information for samples from the Diancangshan Massif. Table S2: Laser ablation–inductively coupled plasma–mass spectrometric zircon U-Pb isotopic analyses of samples along the Diancangshan Massif. Table S3: Trace-elemental concentrations (in ppm) from the analyzed zircons of samples from the Diancangshan Massif. Table S4: Zircon Hf and O isotopic compositions of samples from the Diancangshan Massif. Table S5: Major (wt%) and trace-elemental (ppm) compositions of samples in the Diancangshan Massif.
A QI initiative: implementing a patient handoff checklist for pediatric hospitalist attendings
Authors: Lo Huay-ying , Mullan Paul C. , Lye Cara , Gordon Mary , Patel Binita , Vachani Joyee
Published: March 2024

Handoffs represent a critical transition point in patient care that play a key role in patient safety. Our quality improvement project was a descriptive observational study aimed at standardizing pediatric hospitalist handoffs via implementation of a handoff checklist, with the goal of improving handoff quality and physician satisfaction within six months. The handoff checklist was quickly adapted by hospitalists, with median compliance rate of 83% during the study. Handoff quality was assessed by trained observers using the validated Handoff Clinical Evaluation Exercise (CEX) tool at multiple time periods pre- and post-implementation (at 2, 6, 12, and 24 months). Handoff quality improved during our study, with a significant decrease in the percentage of "unsatisfactory" handoffs from 9% to 0% (p-value 0.004), an effect which was sustained after initial project completion. The cumulative time required for verbal handoffs for different attending physicians paralleled patient census. However, our project identified wasted down time between individual physician handoffs, and an intervention to change shift times led to a decrease in the average total handoff process time from 86 minutes to 60 minutes, p-value <0.001. An average of 7.4 patient care items was identified during handoffs. A physician perception survey revealed improved situational awareness, efficiency, patient safety, and physician satisfaction as a result of our handoff improvement project. In conclusion, implementation of a checklist and standardized handoff process for pediatric hospitalists improved handoff efficiency and quality, as well as physician satisfaction.
Economic Growth and Inflation Tradeoffs within Global Stagflation: Evidence from the Vietnam Economy
Authors: Hung Ly Dai
Published: March 2024

The paper analyzes the interaction of economic growth and inflation rate on accounting for both sources of capital investment and global shocks. The analysis method is a time-varying coefficient Bayesian vector autoregression (TVC-BSVAR) model applied in a quarterly data sample of the Vietnam economy over Q2/2001–Q4/2022. The global factors, including the world economic growth and the inflation rate, are the most important drivers of domestic growth and inflation rate. A greater world growth rate raises the domestic growth rate while a higher world inflation rate increases the domestic inflation rate. If the world economy falls into stagflation with declining growth and a rising inflation rate, Vietnam’s economic growth reduces while the inflation surges. The monetary and fiscal policy can be employed to recover domestic economic growth but with an associated surge in the domestic inflation rate.
PaSTG: A Parallel Spatio-Temporal GCN Framework for Traffic Forecasting in Smart City
Authors: He Xianhao , Hu Yikun , Liao Qing , Xiong Hantao , Yang Wangdong , Li Kenli
Published: March 2024

Predicting future traffic conditions from urban sensor data is crucial for smart city applications. Recent traffic forecasting methods are derived from Spatio-Temporal Graph Convolution Networks (STGCNs). Despite their remarkable achievements, these spatio-temporal models have mainly been evaluated on small-scale datasets. In light of the rapid growth of the Internet of Things and urbanization, cities are witnessing an increased deployment of sensors, resulting in the collection of extensive sensor data to provide more accurate insights into citywide traffic dynamics. Spatio-temporal graph modeling on large-scale traffic data is challenging due to the memory constraint of the computing device. For traffic forecasting, subgraph sampling from road networks onto multiple devices is feasible. Many GCN sampling methods have been proposed recently. However, combining these with STGCNs degrades performance. This is primarily due to prediction biases introduced by each sampled subgraph, which analyze traffic states from a regional perspective.

Addressing these challenges, we introduce a parallel STGCN framework called PaSTG. PaSTG divides the road network into regions, each processed by an individual STGCN in a device. To mitigate regional biases, Aggregation Blocks in PaSTG merge spatial-temporal features from each STBlock. This collaboration enhances traffic forecasting. Furthermore, PaSTG implements pipeline parallelism and employs a graph partition algorithm for optimized pipeline efficiency. We evaluate PaSTG on various STGCNs using three traffic datasets on multiple GPUs. Results demonstrate that our parallel approach applies widely to diverse STGCN models, surpassing existing GCN samplers by up to 57.4% in prediction accuracy. Additionally, the parallel framework achieves speedups of up to 2.87x and 4.70x in training and inference compared to GCN samplers.
Plasmodesmata: Channels Under Pressure
Authors: Bayer Emmanuelle M. , Benitez-Alfonso Yoselin
Published: March 2024

Multicellularity has emerged multiple times in evolution, enabling groups of cells to share a living space and reducing the burden of solitary tasks. While unicellular organisms exhibit individuality and independence, cooperation among cells in multicellular organisms brings specialization and flexibility. However, multicellularity also necessitates intercellular dependence and relies on intercellular communication. In plants, this communication is facilitated by plasmodesmata: intercellular bridges that allow the direct (cytoplasm-to-cytoplasm) transfer of information between cells. Plasmodesmata transport essential molecules that regulate plant growth, development, and stress responses. They are embedded in the extracellular matrix but exhibit flexibility, adapting intercellular flux to meet the plant's needs.

In this review, we delve into the formation and functionality of plasmodesmata and examine the capacity of the plant communication network to respond to developmental and environmental cues. We illustrate how environmental pressure shapes cellular interactions and aids the plant in adapting its growth.
Exosomes as Emerging Regulators of Immune Responses in Type 2 Diabetes Mellitus
Authors: Zheng Wei , Ji Xin , Yin Qiao qiao , Wu Chensi , Xu Chengan , Pan Hongying , Wu Chun
Published: March 2024

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by high blood glucose levels resulting from insulin resistance and impaired insulin secretion. Immune dysregulation‐mediated chronic low‐grade inflammation is a critical factor that poses a significant risk to the metabolic disorders of T2DM and its related complications. Exosomes, as small extracellular vesicles secreted by various cells, have emerged as essential regulators of intercellular communication and immune regulation. In this review, we summarize the current understanding of the role of exosomes derived from immune and nonimmune cells in modulating immune responses in T2DM by regulating immune cell functions and cytokine production. More importantly, we suggest potential strategies for the clinical applications of exosomes in T2DM management, including biomarkers for disease diagnosis and monitoring, exosome‐based therapies for drug delivery vehicles, and targeted therapy for exosomes.
A Comprehensive Review on the Role of Interleukin-40 as a Biomarker for Diagnosing Inflammatory Diseases
Authors: Dabbagh-Gorjani Feryal
Published: March 2024

Interleukins are a group of proteins that have a wide range of complex functions and are believed to be involved in several diseases and conditions. In particular, interleukin-40 (IL-40) is a recently identified cytokine associated with B cells that was first introduced by Catalan et al. in 2017. This cytokine has several roles in the body, including functioning in the formation of B cells in the bone marrow, IgA production, and expression in the intestinal microbiome. Moreover, IL-40 appears to be involved in numerous autoimmune and inflammatory conditions, such as rheumatoid arthritis, systemic lupus erythematosus, primary Sjogren’s syndrome, ankylosing spondylitis, type 2 diabetes, Graves’ disease, and hepatic cell carcinoma. Our understanding of this molecule is quite restricted due to its novelty. However, because of its inflammatory characteristics, there is a high probability that it contributes to a variety of inflammatory disease complications. The aim of the present review is to highlight all available data on the importance of assessing IL-40 levels in human diseases up to now, which could be used as a diagnostic biomarker for the onset or progression of numerous inflammatory diseases.
Smart Predictor for Spontaneous Combustion in Cotton Storages Using Wireless Sensor Network and Machine Learning
Authors: Shafi Umar Farooq , Anwar Waheed , Bajwa Imran Sarwar , Sattar Hina , Yaqoob Iqra , Mahmood Aqsa , Ramzan Shabana
Published: March 2024

The splendid technological inventions supersede many traditional agricultural monitoring systems. In the last decade, a variety of new techniques and tools are proposed to monitor storage areas, which provide more safe and secure storage for different crops. The term storage area monitoring is supposed to check and avoid fire hazards, whereas numerous other hazards also need attention. One such hazard to cotton storage is spontaneous combustion, a process by which an element having comparatively low ignition temperature (hay, straw, peat, etc.) starts to relieve heat. In the presence of spontaneous combustion and lack of oxygen, if cotton catches any sparks from bales or physicochemical heat to ignite, the combustion can convert in to smoldering, and it can last up to several days without being discovered. Consequently, the actual fire occurs, cotton silently smoldering which not only affects cotton quality but also became the reason of big fire event. Many researchers propose valuable tools and techniques based on laboratory methods and modern techniques as well for detection and prevention of security hazards in storages. However, there is no standalone efficient tool/technique to monitor the storage area for spontaneous combustion. In current research, we propose an efficient wireless sensor network (WSN) and machine learning- (ML-) based storage area monitoring system for early prediction of spontaneous combustion in the cotton storage area. The WSN is used to collect real-time values from storage field by different combinations of sensors and send this over the network, where data is processed to identify spontaneous combustion and distribute the prediction results to the end user. The real-time data collection and ML-based analysis make the system efficient and reliable. The efficiency of the current system is verified by presenting two groups of cotton stored with different conditions. The results showed that the proposed system is able to detect spontaneous combustion well in time with a 95% accuracy rate.
Liquid-State Fermented Ganoderma lucidum GANO99 Regulates Gut Microbiota and Concomitantly Modulates the Behavioral Deficits and Neurohistopathological Hallmarks of Alzheimer’s Disease in a Preclinical Transgenic Mouse Model of Alzheimer’s Disease
Authors: Chen Wei-Jen , Wei Yu-Shan , Lo Hsin-I. , Chu Hui-Fang , Tseng Ming-Chung , Lee Bao-Hong , Shen Tang-Long
Published: March 2024

Amyloid beta (Aβ) is a neuropathological hallmark of Alzheimer’s disease (AD). Oxidative stress promotes intracellular accumulation of Aβ in patients with AD. The effects of liquid-state fermentation products of Ganoderma lucidum without mycelia on AD improvement or prevention have not been reported. Therefore, this study aimed to determine whether the liquid-state fermented products of G. lucidum GANO99 can alter AD pathology in the brains of APPNL-G-F/NL-G-F model mice. Our results suggest that these products promote the expression of superoxide dismutase and inhibit the expression of Aβ and glial fibrillary acidic protein, thereby affecting behavioral, learning, and memory disorders in AD mice. In contrast, G. lucidum GANO99 may regulate the gut microbiota to improve AD pathology. Furthermore, these liquid-state fermented products increased the abundance of intestinal probiotics Bifidobacterium in AD mice. Clinical evidence suggests that these lactic acid bacteria can alleviate AD. Overall, the liquid-state fermented products of G. lucidum GANO99 can act as symbionts by reducing the fermentative role of intestinal microbes and chemo-heterotrophy in AD mice.
A Cross-Sectional Study of General Nutrition Knowledge among Nursing Students in the UAE
Authors: Ibrahim Rasha A. K. , Aldawsari Aisha N.
Published: March 2024

Background. Adolescence is a crucial time for establishing long-lasting healthy habits, but many university students often engage in unhealthy eating behaviors. Increased independence, social influences, and mental stress all play a role in leading to poor dietary choices that can impact overall health and well-being. It is important to have a good grasp of nutrition to make informed food choices and avoid the development of chronic illnesses. Purpose. To assess the nutrition knowledge of nursing students and examine the interconnections between participants’ beliefs about diet, disease, and weight management Methods: A total of 100 nursing students participated in this descriptive cross-sectional study. Data gathering was conducted from March 2023 to May 2023 at a nursing college in the UAE. Participating students completed a self-reported validated revised general nutrition knowledge questionnaire (GNKQ-R). Descriptive statistics and Pearson’s correlation were used for analysis, along with univariate and multivariate analyses as a statistical methodology to examine individual variables within the dataset independently. Cronbach’s alpha coefficient of the scale in this study is 0.880. A cut-off point of 50 percent correctness was employed to signify a high level of knowledge. Results. All participating students were female, with the majority (94%) being single. Most students (68%) had a normal mass index of 23.6, whereas 32% were overweight. The analysis showed that more than half of the students (57%) rated their overall health condition as good. The analysis also found that the only variable detected to predict the good nutrition knowledge level among studied students was having children less than 18 in the same family. Conclusion. The results of the current study indicate that future wellness actions should prioritize increasing students’ general nutrition knowledge while also considering individual and academic factors impacting NK in college.
Development and Nutritional Evaluation of Ready-to-Drink Beverage Using the Choongan (Caralluma tuberculata L.) Extract
Authors: Noor Nabia , Din Ghulam Mueen Ud , Nadeem Muhammad , Qureshi Tahir Mahmood , Khalid Waseem , Nadeem Muhammad Ather , Iqbal Aqsa , Malik Faiqa , AL-Farga Ammar , Aqlan Faisal
Published: March 2024

The present study aimed to develop ready-to-drink (RTD) beverage using the choongan (Caralluma tuberculata L.) extract and further to evaluate antioxidant potential and mineral estimation of the prepared RTD. The stem of Caralluma tuberculata was used to further isolate and purify the powder. Then, C. tuberculata powder was utilized in the formulation of beverages. All the treatments observed a decreasing trend for acidity, total soluble solids, total phenols, total antioxidant activity, total flavonoids, DPPH radical scavenging activity, and viscosity during storage whilst pH showed an increasing trend. It was observed that Caralluma RTD contained increasing trend of phytochemicals by increasing contents of the Caralluma extract. The same trend was also observed regarding all the mineral contents investigated in the present study. The treatment T4 (Caralluma RTD having 1.5 g C. tuberculata powder) showed the maximum values regarding phytochemicals as well as minerals. The microbial counts (log10 CFU/mL) for all the treatments increased during storage. Even though T4 showed promising results regarding phytochemicals and minerals, T1 showed the maximum sensory score even after 21 days of storage.
Evaluation and Performance Testing of Eccentric Rolling Isolation System
Authors: Yang Cho-Yen , Chiao Dan , Lai Yong-An , Chang Chia-Ming , Chung Lap-Loi
Published: March 2024

Seismic isolation has become a widely accepted method for the protection of structures and nonstructural components. However, this control strategy is unfavorable against near‐fault earthquakes, particularly those featuring velocity‐pulse effects. Excessive isolation displacements and accelerations can occur during such earthquakes, resulting in amplified responses of the superstructure. To resolve this problem, this study develops a prototype of the eccentric rolling isolation system consisting of one platform eccentrically pin‐connected to four circular rollers. The eccentric pin connection yields a nonlinear restoring force of the proposed system and results in displacement‐dependent resonances, and the inherent mechanical friction also yields an energy dissipation capability of the system. As the magnitude of ground excitation increases, the prototype system generates a lower resonant frequency away from the dominant frequencies of earthquakes. This behavior is experimentally investigated and verified for mechanical behavior and seismic performance. In the experiment, sinusoidal, far‐field, and near‐fault ground motions are considered in shaking table testing. Some parameters, such as the eccentricity, roller size, and inertial force, are also experimentally investigated. As found in the experimental result, the feasibility of the prototype system is successfully verified. Meanwhile, the comparable simulation results further validate the mathematical model of the prototype system. Consequently, the eccentric rolling isolation system has demonstrated isolation effectiveness against far‐field ground motions and has good potential to perform better than a linear system under near‐fault ground motions.
Urdu Translation and Cross-Cultural Adaptation of Canadian Assessment of Physical Literacy-2 (CAPL-2) Questionnaires: A Reliability Analysis in Pakistani Children
Authors: Hadier Syed Ghufran , Yinghai Liu , Long Liu , Hamdani Syed Muhammad Zeeshan Haider , Khurram Haris , Hamdani Syed Danish , Danish Shaista Shireen , Fatima Syeda Urooj , Guo Yanlan
Published: March 2024

Background. Physical literacy is vital for addressing children’s health issues such as childhood obesity, physical inactivity, and sedentary behavior. However, there is a lack of research on PL assessment in Pakistan. This study is aimed at translating and cross-culturally adapting the Canadian Assessment of Physical Literacy-2 (CAPL-2) tool and establishing its validity and reliability in the Pakistani population. Methods. The CAPL-2 was translated to Urdu employing the translation and back translation method. A cross-sectional study involving 350 school children (8-12 years) from Multan, South Punjab, evaluated the CAPL-2U version’s reliability. Results. Expert consensus and pilot testing successfully achieved translation, cross-cultural adaptation, face and content validity. The CAPL-2U demonstrated excellent reliability and internal consistency across the domains. Specifically, daily behavior domain had an internal consistency ofα=0.964and test-retest reliability ofICC=0.930. Knowledge and understanding domain showed internal consistency ranging fromα=0.906to 0.986 and test-retest reliability ofICC=0.827to 0.986. The motivation and confidence domain had an internal consistency ofα=0.923to 0.997 and test-retest reliability ofICC=0.857to 0.993. The correlation between test-retest results for knowledge and understanding and motivation and confidence domains wasr=0.318to 0.973. However, two items in the motivation and confidence domain showed discrepancies in test-retest outcomes. Conclusion. The study confirms the successful translation and adaptation of the CAPL-2 questionnaire for use in Urdu and Pakistani contexts. The findings endorse the tool’s reliability and suitability for assessing physical literacy in Pakistan’s children aged 8-12.
Supplementary Table S6 from Lung Cancer in Ever- and Never-Smokers: Findings from Multi-Population GWAS Studies
Authors: Li Yafang , Xiao Xiangjun , Li Jianrong , Han Younghun , Cheng Chao , Fernandes Gail F. , Slewitzke Shannon E. , Rosenberg Susan M. , Zhu Meng , Byun Jinyoung , Bossé Yohan , McKay James D. , Albanes Demetrios , Lam Stephen , Tardon Adonina , Chen Chu , Bojesen Stig E. , Landi Maria T. , Johansson Mattias , Risch Angela , Bickeböller Heike , Wichmann H-Erich , Christiani David C. , Rennert Gad , Arnold Susanne M. , Goodman Gary E. , Field John K. , Davies Michael P.A. , Shete Sanjay , Marchand Loïc Le , Liu Geoffrey , Hung Rayjean J. , Andrew Angeline S. , Kiemeney Lambertus A. , Sun Ryan , Zienolddiny Shanbeh , Grankvist Kjell , Johansson Mikael , Caporaso Neil E. , Cox Angela , Hong Yun-Chul , Lazarus Philip , Schabath Matthew B. , Aldrich Melinda C. , Schwartz Ann G. , Gorlov Ivan , Purrington Kristen S. , Yang Ping , Liu Yanhong , Bailey-Wilson Joan E. , Pinney Susan M. , Mandal Diptasri , Willey James C. , Gaba Colette , Brennan Paul , Xia Jun , Shen Hongbing , Amos Christopher I.
Published: March 2024

Supplementary Table S6 displays epigenomic evidence for the variants being located within genomic regions associated with regulatory activity.
Supplementary Figure 1 from Genome-Wide Gene–Environment Interaction Analyses to Understand the Relationship between Red Meat and Processed Meat Intake and Colorectal Cancer Risk
Authors: Stern Mariana C. , Sanchez Mendez Joel , Kim Andre E. , Obón-Santacana Mireia , Moratalla-Navarro Ferran , Martín Vicente , Moreno Victor , Lin Yi , Bien Stephanie A. , Qu Conghui , Su Yu-Ru , White Emily , Harrison Tabitha A. , Huyghe Jeroen R. , Tangen Catherine M. , Newcomb Polly A. , Phipps Amanda I. , Thomas Claire E. , Kawaguchi Eric S. , Lewinger Juan Pablo , Morrison John L. , Conti David V. , Wang Jun , Thomas Duncan C. , Platz Elizabeth A. , Visvanathan Kala , Keku Temitope O. , Newton Christina C. , Um Caroline Y. , Kundaje Anshul , Shcherbina Anna , Murphy Neil , Gunter Marc J. , Dimou Niki , Papadimitriou Nikos , Bézieau Stéphane , van Duijnhoven Franzel J.B. , Männistö Satu , Rennert Gad , Wolk Alicja , Hoffmeister Michael , Brenner Hermann , Chang-Claude Jenny , Tian Yu , Le Marchand Loïc , Cotterchio Michelle , Tsilidis Konstantinos K. , Bishop D. Timothy , Melaku Yohannes Adama , Lynch Brigid M. , Buchanan Daniel D. , Ulrich Cornelia M. , Ose Jennifer , Peoples Anita R. , Pellatt Andrew J. , Li Li , Devall Matthew A.M. , Campbell Peter T. , Albanes Demetrius , Weinstein Stephanie J. , Berndt Sonja I. , Gruber Stephen B. , Ruiz-Narvaez Edward , Song Mingyang , Joshi Amit D. , Drew David A. , Petrick Jessica L. , Chan Andrew T. , Giannakis Marios , Peters Ulrike , Hsu Li , Gauderman W. James
Published: March 2024

Forest plots of meta-analysis of association between read meat and processed meat intake with colorectal cancer, and funnel plots for read meat and processed meat intake.
Data from Lung Cancer in Ever- and Never-Smokers: Findings from Multi-Population GWAS Studies
Authors: Li Yafang , Xiao Xiangjun , Li Jianrong , Han Younghun , Cheng Chao , Fernandes Gail F. , Slewitzke Shannon E. , Rosenberg Susan M. , Zhu Meng , Byun Jinyoung , Bossé Yohan , McKay James D. , Albanes Demetrios , Lam Stephen , Tardon Adonina , Chen Chu , Bojesen Stig E. , Landi Maria T. , Johansson Mattias , Risch Angela , Bickeböller Heike , Wichmann H-Erich , Christiani David C. , Rennert Gad , Arnold Susanne M. , Goodman Gary E. , Field John K. , Davies Michael P.A. , Shete Sanjay , Marchand Loïc Le , Liu Geoffrey , Hung Rayjean J. , Andrew Angeline S. , Kiemeney Lambertus A. , Sun Ryan , Zienolddiny Shanbeh , Grankvist Kjell , Johansson Mikael , Caporaso Neil E. , Cox Angela , Hong Yun-Chul , Lazarus Philip , Schabath Matthew B. , Aldrich Melinda C. , Schwartz Ann G. , Gorlov Ivan , Purrington Kristen S. , Yang Ping , Liu Yanhong , Bailey-Wilson Joan E. , Pinney Susan M. , Mandal Diptasri , Willey James C. , Gaba Colette , Brennan Paul , Xia Jun , Shen Hongbing , Amos Christopher I.
Published: March 2024

AbstractBackground:
Clinical, molecular, and genetic epidemiology studies displayed remarkable differences between ever- and never-smoking lung cancer.
Methods:
We conducted a stratified multi-population (European, East Asian, and African descent) association study on 44,823 ever-smokers and 20,074 never-smokers to identify novel variants that were missed in the non-stratified analysis. Functional analysis including expression quantitative trait loci (eQTL) colocalization and DNA damage assays, and annotation studies were conducted to evaluate the functional roles of the variants. We further evaluated the impact of smoking quantity on lung cancer risk for the variants associated with ever-smoking lung cancer.
Results:
Five novel independent loci, GABRA4, intergenic region 12q24.33, LRRC4C, LINC01088, and LCNL1 were identified with the association at two or three populations (P < 5 × 10−8). Further functional analysis provided multiple lines of evidence suggesting the variants affect lung cancer risk through excessive DNA damage (GABRA4) or cis-regulation of gene expression (LCNL1). The risk of variants from 12 independent regions, including the well-known CHRNA5, associated with ever-smoking lung cancer was evaluated for never-smokers, light-smokers (packyear ≤ 20), and moderate-to-heavy-smokers (packyear > 20). Different risk patterns were observed for the variants among the different groups by smoking behavior.
Conclusions:
We identified novel variants associated with lung cancer in only ever- or never-smoking groups that were missed by prior main-effect association studies.
Impact:
Our study highlights the genetic heterogeneity between ever- and never-smoking lung cancer and provides etiologic insights into the complicated genetic architecture of this deadly cancer.
Supplementary Table S11 from Spatial Gene-Expression Profiling Unveils Immuno-oncogenic Programs of NF1-Associated Peripheral Nerve Sheath Tumor Progression
Authors: Mitchell Dana K. , Burgess Breanne , White Emily E. , Smith Abbi E. , Sierra Potchanant Elizabeth A. , Mang Henry , Hickey Brooke E. , Lu Qingbo , Qian Shaomin , Bessler Waylan , Li Xiaohong , Jiang Li , Brewster Kylee , Temm Constance , Horvai Andrew , Albright Eric A. , Fishel Melissa L. , Pratilas Christine A. , Angus Steven P. , Clapp D. Wade , Rhodes Steven D.
Published: March 2024

List of Normal Nerve and MPNST samples obtained from XenaBrowser.net
Supplementary Figure S4 from Spatial Gene-Expression Profiling Unveils Immuno-oncogenic Programs of NF1-Associated Peripheral Nerve Sheath Tumor Progression
Authors: Mitchell Dana K. , Burgess Breanne , White Emily E. , Smith Abbi E. , Sierra Potchanant Elizabeth A. , Mang Henry , Hickey Brooke E. , Lu Qingbo , Qian Shaomin , Bessler Waylan , Li Xiaohong , Jiang Li , Brewster Kylee , Temm Constance , Horvai Andrew , Albright Eric A. , Fishel Melissa L. , Pratilas Christine A. , Angus Steven P. , Clapp D. Wade , Rhodes Steven D.
Published: March 2024

Supplemental Figure 4. Enhanced transcriptional signatures of angiogenesis and tumor vascularity in MPNST.
Table S33 from CD46-Targeted Theranostics for PET and 225Ac-Radiopharmaceutical Therapy of Multiple Myeloma
Authors: Wadhwa Anju , Wang Sinan , Patiño-Escobar Bonell , Bidkar Anil P. , Bobba Kondapa Naidu , Chan Emily , Meher Niranjan , Bidlingmaier Scott , Su Yang , Dhrona Suchi , Geng Huimin , Sarin Vishesh , VanBrocklin Henry F. , Wilson David M. , He Jiang , Zhang Li , Steri Veronica , Wong Sandy W. , Martin Thomas G. , Seo Youngho , Liu Bin , Wiita Arun P. , Flavell Robert R.
Published: March 2024

Table S33: %IA/g of [89Zr]Zr-DFO-IgG in systemic MM.1S tumor model.
Table S21 from CD46-Targeted Theranostics for PET and 225Ac-Radiopharmaceutical Therapy of Multiple Myeloma
Authors: Wadhwa Anju , Wang Sinan , Patiño-Escobar Bonell , Bidkar Anil P. , Bobba Kondapa Naidu , Chan Emily , Meher Niranjan , Bidlingmaier Scott , Su Yang , Dhrona Suchi , Geng Huimin , Sarin Vishesh , VanBrocklin Henry F. , Wilson David M. , He Jiang , Zhang Li , Steri Veronica , Wong Sandy W. , Martin Thomas G. , Seo Youngho , Liu Bin , Wiita Arun P. , Flavell Robert R.
Published: March 2024

Table S21: [18F]-FDG %IA/g in the ANBL6 subcutaneous xenograft models.
Table S12 from CD46-Targeted Theranostics for PET and 225Ac-Radiopharmaceutical Therapy of Multiple Myeloma
Authors: Wadhwa Anju , Wang Sinan , Patiño-Escobar Bonell , Bidkar Anil P. , Bobba Kondapa Naidu , Chan Emily , Meher Niranjan , Bidlingmaier Scott , Su Yang , Dhrona Suchi , Geng Huimin , Sarin Vishesh , VanBrocklin Henry F. , Wilson David M. , He Jiang , Zhang Li , Steri Veronica , Wong Sandy W. , Martin Thomas G. , Seo Youngho , Liu Bin , Wiita Arun P. , Flavell Robert R.
Published: March 2024

Table S12: [89Zr]Zr-DFO-IgG %IA/Organ in the RPMI8226 subcutaneous xenograft models.
Figure S8 from CD46-Targeted Theranostics for PET and 225Ac-Radiopharmaceutical Therapy of Multiple Myeloma
Authors: Wadhwa Anju , Wang Sinan , Patiño-Escobar Bonell , Bidkar Anil P. , Bobba Kondapa Naidu , Chan Emily , Meher Niranjan , Bidlingmaier Scott , Su Yang , Dhrona Suchi , Geng Huimin , Sarin Vishesh , VanBrocklin Henry F. , Wilson David M. , He Jiang , Zhang Li , Steri Veronica , Wong Sandy W. , Martin Thomas G. , Seo Youngho , Liu Bin , Wiita Arun P. , Flavell Robert R.
Published: March 2024

Figure S8: Bioluminescence Images of NSG mouse showed an increase in tumor burden gradually injected with different doses of [225Ac]Ac-DOTA-YS5 from each group and saline group.
Figure S5 from CD46-Targeted Theranostics for PET and 225Ac-Radiopharmaceutical Therapy of Multiple Myeloma
Authors: Wadhwa Anju , Wang Sinan , Patiño-Escobar Bonell , Bidkar Anil P. , Bobba Kondapa Naidu , Chan Emily , Meher Niranjan , Bidlingmaier Scott , Su Yang , Dhrona Suchi , Geng Huimin , Sarin Vishesh , VanBrocklin Henry F. , Wilson David M. , He Jiang , Zhang Li , Steri Veronica , Wong Sandy W. , Martin Thomas G. , Seo Youngho , Liu Bin , Wiita Arun P. , Flavell Robert R.
Published: March 2024

Figure S5: Targeted radioligand therapy with [225Ac]Ac-DOTA-YS5 demonstrates high treatment efficacy in the MM.1S subcutaneous MM model.
Figure S3 from CD46-Targeted Theranostics for PET and 225Ac-Radiopharmaceutical Therapy of Multiple Myeloma
Authors: Wadhwa Anju , Wang Sinan , Patiño-Escobar Bonell , Bidkar Anil P. , Bobba Kondapa Naidu , Chan Emily , Meher Niranjan , Bidlingmaier Scott , Su Yang , Dhrona Suchi , Geng Huimin , Sarin Vishesh , VanBrocklin Henry F. , Wilson David M. , He Jiang , Zhang Li , Steri Veronica , Wong Sandy W. , Martin Thomas G. , Seo Youngho , Liu Bin , Wiita Arun P. , Flavell Robert R.
Published: March 2024

Figure S3:[89Zr]Zr-DFO-YS5 demonstrates favorable PET imaging characteristics in the RPMI8226 systemic model.
Supplementary Figure 1 from Niraparib plus Dostarlimab in Pleural Mesothelioma or Non–Small Cell Lung Cancer Harboring HRR Mutations: Interim Results of the UNITO-001 Phase II Prospective Trial
Authors: Passiglia Francesco , Righi Luisella , Bironzo Paolo , Listì Angela , Farinea Giovanni , Capelletto Enrica , Novello Silvia , Merlini Alessandra , Scagliotti Giorgio V.
Published: March 2024

Supplementary Figure 1. ID patients 10# IGV screen of BAP1 c.38-1G>T variant.
Supplementary Figure 3 from Single-Cell Transcriptomics Reveals Pre-existing COVID-19 Vulnerability Factors in Lung Cancer Patients
Authors: Liu Wendao , Li Wenbo , Zhao Zhongming
Published: March 2024

Supplementary Figure 3. Macrophage subpopulations and functional characterization.
Data from Single-Cell RNA-Seq Analysis of Patient Myeloid-Derived Suppressor Cells and the Response to Inhibition of Bruton's Tyrosine Kinase
Authors: Savardekar Himanshu , Allen Carter , Jeon Hyeongseon , Li Jianying , Quiroga Dionisia , Schwarz Emily , Wu Richard C. , Zelinskas Sara , Lapurga Gabriella , Abreo Alexander , Stiff Andrew , Shaffer Jami , Blaser Bradley W. , Old Matthew , Wesolowski Robert , Xin Gang , Kendra Kari L. , Chung Dongjun , Carson William E.
Published: March 2024

Abstract
Myeloid-derived suppressor cell (MDSC) levels are elevated in patients with cancer and contribute to reduced efficacy of immune checkpoint therapy. MDSC express Bruton's tyrosine kinase (BTK) and BTK inhibition with ibrutinib, an FDA-approved irreversible inhibitor of BTK, leads to reduced MDSC expansion/function in mice and significantly improves the antitumor activity of anti-PD-1 antibody treatments. Single-cell RNA sequencing (scRNA-seq) was used to characterize the effect of ibrutinib on gene expression of fluorescence-activated cell sorting-enriched MDSC from patients with different cancer types [breast, melanoma, head and neck squamous cell cancer (HNSCC)]. Melanoma patient MDSC were treated in vitro for 4 hours with 5 μmol/L ibrutinib or DMSO, processed for scRNA-seq using the Chromium 10× Genomics platform, and analyzed via the Seurat v4 standard integrative workflow. Baseline gene expression of MDSC from patients with breast, melanoma, and HNSCC cancer revealed similarities among the top expressed genes. In vitro ibrutinib treatment of MDSC from patients with melanoma resulted in significant changes in gene expression. GBP1, IL-1β, and CXCL8 were among the top downregulated genes whereas RGS2 and ABHD5 were among the top upregulated genes (P < 0.001). Double positive CD14+CD15+ MDSC and PMN-MDSC responded similarly to BTK inhibition and exhibited more pronounced gene changes compared with early MDSC and M-MDSC. Pathway analysis revealed significantly downregulated pathways including TREM1, nitric oxide signaling, and IL-6 signaling (P < 0.004).
Implications:
scRNA-seq revealed characteristic gene expression patterns for MDSC from different patients with cancer and BTK inhibition led to the downregulation of multiple genes and pathways important to MDSC function and migration.
Abstract B007: Investigation of the mechanism of PADI2 regulation by the FBXW7 tumor suppressor
Authors: Kafle Chandra Mani , Bell Daphne W.
Published: March 2024

Serous endometrial cancer (SEC) is an aggressive form of cancer that frequently exhibits recurrent somatic mutations in FBXW7 at residues 465, 479, and 505. FBXW7 is a tumor suppressor and is part of a Skp1-Cullin-F-box containing (SCF) complex that targets various proteins, including certain oncoproteins, for ubiquitin-mediated proteasomal degradation. FBXW7 interacts with Cdc4 phosphodegron (CPD) motif(s) within substrate proteins. We previously reported upregulation of peptidyl arginine deiminase 2 (PADI2), a potentially druggable protein, in FBXW7-mutant SEC cell lines compared to the isogenic FBXW7-wildtype cells. The purpose of this study is to investigate the mechanism by which FBXW7 regulates PADI2 levels. We searched for the CPD motif in the PADI2 protein sequence. We used co-immunoprecipitation and immunoblotting to study FBXW7-PADI2 interactions after transiently transfecting HEK293 cells with constructs expressing MYC-tagged FBXW7 and/or HA-tagged PADI2, in the presence or absence of bortezomib. We identified three putative CPD motifs in PADI2, leading us to hypothesize that wildtype FBXW7 binds PADI2 and thus targets PADI2 for degradation via a proteasome-dependent mechanism. Our experimental data show that FBXW7 interacts with PADI2, in the presence of bortezomib, a proteasome inhibitor, in transiently transfected HEK293 cells. Additionally, we have shown that mutation of the putative CPD motifs of PADI2 abrogates the PADI2-FBXW7 interaction. Our findings implicate PADI2 as a novel substrate of the FBXW7 tumor suppressor.

Citation Format: Chandra Mani Kafle, Daphne W. Bell. Investigation of the mechanism of PADI2 regulation by the FBXW7 tumor suppressor [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr B007.
Abstract B016: Novel curcumin analogues as therapies for endometrial cancer with TP53 mutations
Authors: Leslie Kimberly K. , Goss Alex , Padilla Jamie , Smith Lane E.
Published: March 2024

The protein p53 is designated as the guardian of the genome because it is the principal tumor suppressor and functions to surveil the genome, enforce cell cycle checkpoints, and trigger apoptosis when genomic instability is beyond repair. Mutations in TP53 are found in >50% of human tumors and in 25% of the deadliest endometrial malignancies. Yet, few studies have targeted the mutant protein to restore its wild type (WT) tumor suppressor functions. Curcumin, a turmeric derivative, has been shown to help return WT function to mutant p53. However, curcumin is not bioavailable to most of the body because of its water insolubility, hydrophobic nature and rapid metabolization. Our laboratory is testing novel, more bioavailable analogs of curcumin including HO-3867 and AKT-100. In these studies, we tested these agents in preclinical models of serous endometrial cancer to assess their effects on cell growth and p53-dependent signaling. We used CyQUANT cell proliferation assay to identify IC50 values for HO-3867 and AKT-100 in ECC-1 and KLE endometrial cancer cell lines. We performed RNA sequencing to elucidate mechanisms of action and verified p53 expression changes via Western blotting. IC50 values ranged from 100 nanomolar (AKT-100) to low micromolar (HO-3867). RNA sequencing data revealed the re-enforcement of cell cycle checkpoints including the upregulation of CDKN1A (p21) and GADD45 (Gadd45). Proliferative signaling downstream of ATM, an important protein kinase stimulating cell growth, was downregulated by both agents. Western blotting confirmed the classic negative feedback loop of p53, where total p53 levels decreased after drug treatment. Taken together, our findings show that AKT-100 and HO-3867 are able to restore WT tumor suppressor function in otherwise oncogenic mutant p53 by reducing cell replication and promoting apoptosis. Thus, curcumin analogues such as AKT-100 and HO-3867 show promise in the treatment of a subset of endometrial tumors expressing mutant p53 by returning WT p53 functionality, and future studies will move to in vivo analyses of curcumin analogue function.

Citation Format: Kimberly K. Leslie, Alex Goss, Jamie Padilla, Lane E. Smith. Novel curcumin analogues as therapies for endometrial cancer with TP53 mutations [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr B016.
Abstract IA021: Novel genomic features of POLE-mutant tumors: the utility for tumor classification and identification of new driver alleles
Authors: Ostroverkhova Daria , Tyryshkin Kathryn , Beach Annette K. , Moore Elizabeth A. , Masoudi-Sobhanzadeh Yosef , Barbari Stephanie R. , Rogozin Igor B , Shaitan Konstantin V , Panchenko Anna R , Shcherbakova Polina V.
Published: March 2024

Alterations in the exonuclease domain of POLE drive the development of ultramutated endometrial tumors with better prognosis. A hallmark of these tumors is the accumulation of G>T mutations in AGA sequences; however, understanding of their genomic features beyond the trinucleotide motifs is limited. We applied a novel computational framework to the whole-exome sequencing data of 524 endometrial tumors reported by The Cancer Genome Atlas network to analyze the extended DNA sequence context of ultramutation. We found that the presence of POLE driver alleles is associated with an increased frequency of G>T mutations in polypurine tracts. Sequences containing three consecutive purines, including the classic AGA context, are only moderately mutable, but the mutability increased abruptly as the tract length reached six or more purines. Moreover, mutations showed a strong preference for certain positions within the tracts, creating a characteristic quantifiable pattern. Using this signature, we developed a machine learning classifier to identify tumors with hitherto unknown POLE drivers and validated two new drivers, POLE-E978G and POLE-S461L, by functional assays in yeast. Unlike previously known pathogenic variants, the E978G substitution affects the DNA polymerase rather than exonuclease domain of POLE. We further show that the extended genomic signature of POLE ultramutation is shared by tumors with POLD1 drivers. These findings uncover new mechanisms of ultramutation and highlight the limitations of the current focus on POLE exonuclease domain variants when stratifying patients.

Citation Format: Daria Ostroverkhova, Kathryn Tyryshkin, Annette K. Beach, Elizabeth A. Moore, Yosef Masoudi-Sobhanzadeh, Stephanie R. Barbari, Igor B Rogozin, Konstantin V Shaitan, Anna R Panchenko, Polina V. Shcherbakova. Novel genomic features of POLE-mutant tumors: the utility for tumor classification and identification of new driver alleles [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr IA021.