bluuebunny/crossref_metadata_2025 huggingface dataset:
Multicenter validation of artificial intelligence software predicting large vessel occlusion using noncontrast brain CT
Authors: Chung Jong-Won , Lee Myungjae , Ha Sue Young , Kim Pyeong Eun , Sunwoo Leonard , Kim Nakhoon , Park Kwang-Yeol , Yum Kyu Sun , Shin Dong-Ick , Park Hong-Kyun , Cho Yong-Jin , Hong Keun-Sik , Kim Jae Guk , Lee Soo Joo , Kim Joon-Tae , Seo Woo-Keun , Bang Oh Young , Kim Gyeong-Moon , Kim Dongmin , Bae Hee- Joon , Ryu Wi-Sun , Kim Beom Joon
Published: July 2024

Background

To validate JLK-CTL, an artificial intelligence (AI) software developed to predict large vessel occlusion (LVO) using non-contrast CT (NCCT) scans, and to investigate its clinical implications regarding both infarct volume and functional outcomes.

Methods

Between January-2021 and April-2023, a consecutive series of patients who concurrently underwent CT angiography and NCCT within 24 hours of last- known-well (LKW) were collected. LVO was confirmed through consensus among three experts reviewing CT angiography. Infarct volumes were quantified using diffusion-weighted imaging (DWI) conducted within seven days of the NCCT. The performance of the JLK-CTL was evaluated based on the area under the receiver operating characteristic curve (AUROC), as well as its sensitivity and specificity. The association of JLK-CTL LVO scores with infarct volumes and functional outcomes was assessed using Pearson correlation and logistic regression analyses, respectively.

Results

Of 1,391 screened patients, 774 (mean age 69.0 ± 13.6 years, 57.6% men) were included. The median time from LKW to NCCT was 3.1 hours (IQR 1.5–7.4), with 24.2% (n=187) presenting LVO. The JLK-CTL demonstrated AUROC of 0.832 (95% CI 0.804–0.858), with a sensitivity of 0.711 (95% CI 0.641–0.775) and a specificity of 0.830 (95% CI 0.797–0.859) at the predefined threshold. Incorporating the National Institute of Health Stroke Scale into the model increased the AUROC to 0.872 (95% CI 0.846–0.894; p<0.001). The LVO scores showed a significant correlation with infarct volumes on follow-up DWI (r=0.53; p<0.001). When JLK-CTL LVO scores were categorized based on observed frequency of LVO, the highest JLK-CTL LVO scores (51-100) group showed an independent association with unfavorable functional outcomes (adjusted odds ratio 9.48; 95% CI 3.98–22.55).

Conclusion

The performance of the AI software in predicting LVO was validated across multiple centers. This tool has the potential to assist physicians in optimizing stroke management workflows, especially in resource-limited settings.
Harnessing CRISPR/Cas12a Technology to Combat Wheat Dwarf Virus Without Genetic Modification
Authors: Baran Buse , Teymur Tarık , Morca Ali Ferhan , Konuk Muhsin , Taştan Cihan
Published: July 2024

Wheat (Triticum aestivumL.) is a staple crop globally, but its yield and quality are significantly affected by viral diseases, particularly the Wheat Dwarf Virus (WDV). Developing antiviral strategies is crucial for enhancing wheat productivity. This study aims to investigate the use of CRISPR/Cas12a as an antiviral agent against WDV without the need for genetic modification of the host plants. WDV genomic DNAs were isolated from wheat and barley samples collected from various regions in Turkey and other countries. Guide RNAs (gRNAs) targeting conserved regions in the coat protein (CP) gene of WDV were designed and synthesized. The CRISPR/Cas12a ribonucleoprotein (RNP) complex was tested for its ability to induce DNA cleavage in WDV genomes through in vitro assays, and results were analysed using agarose gel electrophoresis. The designed gRNAs effectively induced DNA cleavage in WDV genomes, with gRNA1 showing consistent performance across all tested isolates. gRNA2 exhibited variability, successfully targeting seven out of ten isolates. No off-target effects were observed in control assays, confirming the specificity of the gRNAs. The CRISPR/Cas12a system, guided by specifically designed gRNAs, can effectively target and cleave WDV genomes, providing a potent, non-GMO antiviral strategy. This approach has potential applications for managing WDV infections in wheat and barley, highlighting its versatility and effectiveness.
Large-scale genome analyses provide insights into Hymenoptera evolution
Authors: He Chun , Yang Yi , Zhao Xianxin , Li Junjie , Cai Yuting , Peng Lijia , Liu Yuanyuan , Xiong Shijiao , Mei Yang , Yan Zhichao , Wang Jiale , Xiao Shan , Teng Ziwen , Gao Xueke , Xue Hui , Fang Qi , Ye Gongyin , Ye Xinhai
Published: July 2024

The order Hymenoptera includes a large number of species with diverse lifestyles and is known for its significant contributions to natural ecosystems. To better understand the evolution of this diverse order, we performed large-scale comparative genomics on 131 species from 13 superfamilies, covering most representative groups. We used these genomes to reveal an overall pattern of genomic change in terms of gene content and evolutionary rate throughout hymenopteran history. We identified genes that possibly contributed to the evolution of several key innovations, such as parasitoidism, wasp-waist, sting, and secondary phytophagy. We also discovered the distinct genomic trajectories between the clade containing major parasitoid wasps (Parasitoida) and stinging species (Aculeata) since their divergence, which are involved in many aspects of genomic change, such as rapidly evolving gene families, gene gain and loss, and metabolic pathway evolution. In addition, we explored the genomic features accompanying the three independent evolution of secondary phytophagy. Our work provides insights for understanding genome evolution and the genomic basis of diversification in Hymenoptera.
Regulation of the poly(A) Polymerase Star-PAP by a Nuclear Phosphoinositide Signalosome
Authors: Wen Tianmu , Chen Mo , Cryns Vincent L. , Anderson Richard A.
Published: July 2024

Star-PAP is a noncanonical poly(A) polymerase that controls gene expression. Star-PAP was previously reported to bind the phosphatidylinositol 4-phosphate 5-kinase PIPKI⍺ and its product phosphatidylinositol 4,5-bisphosphate, which regulate Star-PAP poly(A) polymerase activity and expression of specific genes. Recent studies have revealed a nuclear PI signaling pathway in which the PI transfer proteins PITP⍺/β, PI kinases and phosphatases bind p53 to sequentially modify protein-linked phosphatidylinositol phosphates and regulate its function. Here we demonstrate that multiple phosphoinositides, including phosphatidylinositol 4-monophosphate and phosphatidylinositol 3,4,5-trisphosphate are also coupled to Star-PAP in response to stress. This is initiated by PITP⍺/β binding to Star-PAP, while the Star-PAP-linked phosphoinositides are modified by PI4KII⍺, PIPKI⍺, IPMK, and PTEN recruited to Star- PAP. The phosphoinositide coupling enhances the association of the small heat shock proteins HSP27/⍺B-crystallin with Star-PAP. Knockdown of the PITPs, kinases, or HSP27 reduce the expression of Star-PAP targets. Our results demonstrate that the PITPs generate Star-PAP-PIPn complexes that are then modified by PI kinases/phosphatases and small heat shock proteins that regulate the linked phosphoinositide phosphorylation and Star-PAP activity in response to stress.
Dynamics of X chromosome hyper-expression and inactivation in male tissues during stick insect development
Authors: Djordjevic Jelisaveta , Tran Van Patrick , Toubiana William , Labédan Marjorie , Dumas Zoé , Aury Jean-Marc , Cruaud Corinne , Istace Benjamin , Labadie Karine , Noel Benjamin , Parker Darren J , Schwander Tanja
Published: July 2024

Differentiated sex chromosomes are frequently associated with major transcriptional changes: the evolution of dosage compensation (DC) to equalize gene expression between the sexes and the establishment of meiotic sex chromosome inactivation (MSCI). Our study investigates the mechanisms and developmental dynamics of dosage compensation and meiotic sex chromosome inactivation in the stick insect speciesT. poppense. Stick insects are characterized by XX/XO sex determination and an X chromosome which likely evolved prior to the diversification of insects over 450 Mya. We generated a chromosome-level genome assembly and analyzed gene expression from various tissues (brain, gut, antennae, leg, and reproductive tract) across developmental stages in both sexes. Our results show that complete dosage compensation is maintained in male somatic tissues throughout development, mediated by upregulation of the single X chromosome. Contrarily, in male reproductive tissues, dosage compensation is present only in the early nymphal stages. As males reach the 4th nymphal stage and adulthood, X-linked gene expression diminishes, coinciding with the onset of MSCI. This reduction is associated with histone modifications indicative of transcriptional silencing, aligning with meiotic progression. These findings reveal the dynamic regulation of X-linked gene expression inT. poppense, and suggest that reduced X-expression in insect testes is generally driven by MSCI rather than an absence of dosage compensation mechanisms. Our work provides critical insights into sex chromosome evolution and the complex interplay of dosage compensation and MSCI across tissues and developmental stages.
The genetics of fruit skin separation in date palm
Authors: Younuskunju Shameem , Mohamoud Yasmin A. , Mathew Lisa Sara , Mayer Klaus F. X. , Suhre Karsten , Malek Joel A.
Published: July 2024

The physical appearance of date palm (Phoenix dactylifera) fruit (dates) is important for its market value. Many date-producing countries experience significant financial losses due to the poor appearance of the fruit, skin separation or puffiness being a major reason. Previous research showed evidence linking the skin separation phenotype to environmental conditions. In this study, we show that there is both an environmental and genetic contribution to the fruit skin separation phenotype. We show that beyond environmental factors, genetics is a strong contributor to the most extreme skin separation in some cultivars. A genome-wide association study was conducted using genome data of 199 samples collected from 14 countries that identified nine genetic loci associated with this phenotype and investigated genes in these regions that may contribute to the phenotype overall. Identifying the genetic factors may help better understand the biology and pathways that lead to the environmental effects on skin separation and improve commercial date production. In conclusion, our key finding is that both environmental and genetic factors contribute to skin separation variation, and improvements in environmental factors alone cannot overcome the extreme level of variation observed in some cultivars.
Towards edge processing of images from insect camera traps
Authors: Bjerge Kim , Karstoft Henrik , Høye Toke T.
Published: July 2024

Insects represent nearly half of all known multicellular species but knowledge about them lacks behind most vertebrate species. In part for this reason, they are often neglected in biodiversity conservation policies and practice. Computer vision tools, such as insect camera traps, for automated monitoring have the potential to revolutionize insect study and conservation. To further advance insect camera trapping and the analysis of their image data, effective image processing pipelines are needed. In this paper, we present a flexible and fast processing pipeline designed to analyse these recordings by detecting, tracking and classifying nocturnal insects in a broad taxonomy of 15 insect classes and resolution of individual moth species. A classifier with anomaly detection is proposed to filter dark, blurred, or partially visible insects that will be uncertain to classify correctly. A simple track-by-detection algorithm is proposed to track classified insects by incorporating feature embeddings, distance and area cost. We evaluated the computational speed and power performance of different edge computing devices (Raspberry Pi’s and NVIDIA Jetson Nano) and compared various time-lapse strategies with tracking. The minimum difference was found for 2-minute time-lapse intervals compared to tracking with 0.5 frames per second, however, for insects with fewer than one detection per night, the Pearson correlation decreases. Shifting from tracking to time-lapse monitoring would reduce the amount of recorded images and be able to perform edge processing of images in real-time on a camera trap with Raspberry Pi. The Jetson Nano is the most energy-efficient solution, capable of real-time tracking at nearly 0.5 fps. Our processing pipeline was applied to more than 5.7 million images recorded at 0.5 frames per second from 12 light camera traps during two full seasons located in diverse habitats, including bogs, heaths and forests.
Enhancing reproducibility and decentralization in single cell research with biocytometry
Authors: Fikar Pavel , Alvarez Laura , Berne Laura , Cienciala Martin , Kan Christopher , Kasl Hynek , Luo Mona , Novackova Zuzana , Ordonez Sheyla , Sramkova Zuzana , Holubova Monika , Lysak Daniel , Avery Lyndsay , Caro Andres A. , Crowder Roslyn N. , Diaz-Martinez Laura A. , Donley David W. , Giorno Rebecca R. , Guttilla Reed Irene K. , Hensley Lori L. , Johnson Kristen C. , Kim Paul , Kim Audrey Y. , LaGier Adriana J. , Newman Jamie J. , Padilla-Crespo Elizabeth , Reyna Nathan S. , Tsotakos Nikolaos , Al-Saadi Noha N. , Appleton Tayler , Arosemena-Pickett Ana , Bell Braden A. , Bing Grace , Bishop Bre , Forde Christa , Foster Michael J. , Gray Kassidy , Hasley Bennett L. , Johnson Kennedy , Jones Destiny Jen’a , LaShall Allison C. , McGuire Kennedy , McNaughton Naomi , Morgan Angelina M. , Norris Lucas , Ossman Landon A. , Rivera-Torres Paollette A. , Robison Madeline E. , Thibodaux Kathryn , Valmond Lescia , Georgiev Daniel
Published: July 2024

Biomedicine today is experiencing a shift towards decentralized data collection, which promises enhanced reproducibility and collaboration across diverse laboratory environments. This inter-laboratory study evaluates the performance of biocytometry, a method utilizing engineered bioparticles for enumerating cells based on their surface antigen patterns. In a decentralized framework, spanning 78 assays conducted by 30 users across 12 distinct laboratories, biocytometry consistently demonstrated significant statistical power in discriminating numbers of target cells at varying concentrations as low as 1 cell per 100,000 background cells. User skill levels varied from expert to beginner capturing a range of proficiencies. Measurement was performed in a decentralized environment without any instrument cross-calibration or advanced user training outside of a basic instruction manual. The results affirm biocytometry to be a viable solution for immunophenotyping applications demanding sensitivity as well as scalability and reproducibility and paves the way for decentralized analysis of rare cells in heterogeneous samples.
Oviductin sets the species-specificity of the mammalian zona pellucida
Authors: de la Fuente Daniel , Maroto Maria , Cajas Yulia N , Cañón-Beltrán Karina , Fernandez-Gonzalez Raul , Munoz-Maceda Ana , Sanchez-Puig Juana M , Blasco Rafael , Cots Paula , Aviles Manuel , Rizos Dimitrios , Gutiérrez-Adán Alfonso
Published: July 2024

The zona pellucida (ZP) is vital for species-specific fertilization as this barrier mediates sperm-oocyte binding. Here, we determined whether sperm from distant mammalian orders (Carnivora, Primates, and Rodentia) could penetrate bovine oocytes by examining the role of bovine oviductal fluid and species-specific oviductal glycoprotein (OVGP1 or oviductin) from bovine, murine, or human sources in modulating the species-specificity of bovine and murine oocytes. Sperm from all the species were found to penetrate intact bovine ovarian oocytes to form hybrid embryos. However, contact with oviductal fluid or bovine, murine, or human OVGP1, conferred the ZP species-specificity, allowing only the penetration of the corresponding sperm regardless of the ZP’s origin. Glycolytic and microstructural analyses revealed that OVGP1 covers the pores present in the ZP and that OVGP1 glycosylation determines sperm specificity. This suggests specific fertilization capacity is acquired in the oviduct through the ZP’s incorporation of specific oviductin.

Teaser

The oocyte zona pellucida needs to interact with an oviduct protein called OVGP1 to ensure that only sperm from the same species can fertilize the egg.
Reporter-based screening identifies RAS-RAF stabilizing mutations as drivers of resistance to broad-spectrum RAS inhibition in colorectal cancer
Authors: Aust Oleksandra , Blanc Eric , Lüthen Mareen , Hollek Viola , Astaburuaga-García Rosario , Klinger Bertram , Trinks Alexandra , Beule Dieter , Papke Bjoern , Horst David , Bluthgen Nils , Sers Christine , Der Channing J , Morkel Markus
Published: July 2024

Secondary resistance limits the clinical effectiveness of mutation-specific RAS inhibitors in colorectal cancer. It is unknown whether broad-spectrum RAS inhibitors meet similar limitations. Here, we identify and categorize mechanisms of resistance to the broad-spectrum active-state RAS inhibitor RMC-7977 in colorectal cancer cell lines. We found that KRAS-mutant colorectal cancer cell lines are universally sensitive to RMC-7977, inhibiting the RAS-RAF-MEK-ERK axis, halting proliferation and in some cases inducing apoptosis. To monitor KRAS downstream effector pathway activity, we developed a compartment-specific dual-color ERK activity reporter system. RMC-7977 treatment reduced reporter activity. However, long-term dose escalation with RMC-7977 revealed multiple patterns of reporter reactivation in emerging resistant cell populations that correlated with phosphorylation states of compartment-specific ERK targets. Cells sorted for high, low, or cytoplasmic reporter activity exhibited distinct patterns of genomic mutations, phospho-protein, and transcriptional activities. Notably, all resistant subpopulations showed dynamic ERK regulation in the presence of the RAS inhibitor, unlike the parental sensitive cell lines. High levels of RAS downstream activities were observed in cells characterized by a KRAS Y71H resistance mutation. In contrast, RAS inhibitor-resistant populations with low, or cytoplasmic ERK reporter reactivation displayed different genetic alterations, among them RAF1 S257L and S259P mutations. Colorectal cancer cells resistant to RMC-7977 and harboring the RAF1 mutation specifically exhibited synergistic sensitivity to concurrent RAS and RAF inhibition. Our findings endorse reporter-assisted screening together with single-cell analyses as a powerful approach for dissecting the complex landscape of therapy resistance. The strategy offers opportunities to develop clinically relevant combinatorial treatments to counteract emergence of resistant cancer cells.
A two-component signature determines which rust fungi secreted proteins are translocated into the cells of the host plant
Authors: Lawrence Gregory J
Published: July 2024

Rust diseases of plants are caused by parasitic fungi that feed off living plant cells by means of haustoria that form within plant cells. These haustoria also secrete a large number of proteins, some of which remain in the matrix surrounding the haustoria while others are translocated through a membrane into the cytoplasm of the plant cell. These latter proteins would be expected to possess a signature marking them out for translocation but, to date, no such signature has been identified. An examination of a set of wheat rust proteins known to be translocated to the cytoplasm of the wheat cell, together with an analysis of 1208 wheat stem rust (Puccinia graminisf. sp.tritici) secretome proteins, provides evidence that the translocation signature contains two components. The first component consists of a positively-charged amino acid at position 1, 2 or 3 (and possibly 4 or greater) upstream of the hydrophobic region in the signal peptide. The second component consists of a positively-charged amino acid at position 21 downstream of the signal peptide. A similar analysis of flax rust (Melampsora lini) secretome proteins indicates that the first component is the same as that of the wheat stem rust secretome proteins but that the second component consists of a positively-charged amino acid at position (16)17-20 downstream of the signal peptide. The flax rust signature may also be employed by wheat stem rust in its pycnial stage when growing on its alternate dicot host, barberry. Being able to identify which rust haustorial secreted proteins go to the plant cytoplasm and which to the extrahaustorial matrix should facilitate work aimed at identifying the function of each of the secreted proteins and, also, work aimed at elucidating the translocation mechanism, an understanding of which could open up new approaches to rust control.
Selective Outcome Reporting in Cancer Studies: A Scoping Review
Authors: Hinkel Jennifer , Heneghan Carl , Bankhead Clare
Published: July 2024

Background

Unbiased reporting of clinical study results is essential for evidence-based medicine. However, Selective Outcome Reporting (SOR) leads to Outcome Reporting Bias (ORB) and is prevalent across disease areas, including oncology. This scoping review aims to: (a) describe the current state of research on SOR in cancer studies, (b) assess the prevalence of SOR, (c) understand methods and definitions used in SOR assessment, (d) map available evidence and identify research gaps, and (e) discuss research and policy implications.

Methods

A systematic literature search was conducted using keywords related to endpoint discrepancies and oncology. Studies were screened, deduplicated, and evaluated. The JBI Critical Appraisal Checklist for Systematic Reviews and Research Synthesis was used for quality assessment.

Results

Six systematic reviews, each including 24 to 217 cancer clinical trials, were analysed. SOR prevalence varied from 4% to 79%, with a median rate of 12%. Definitions of endpoint discrepancies varied, complicating direct comparisons. SOR was identified as over-reporting, under-reporting, or misreporting outcomes.

Conclusion

SOR is a significant issue in oncology clinical trials, with implications for evidence synthesis, clinical practice, and policy. The lack of consistent definitions and detailed protocol reporting contributes to the challenge. Enhancing transparency and standardisation in outcome reporting could mitigate ORB and improve the reliability of clinical evidence. Implications: Future research should focus on consistent SOR definitions and improved protocol transparency. Policymakers and regulators should promote standards to reduce SOR and ensure transparent and trustworthy clinical trial outcomes.
Genomic insight into theComamonas kerstersiiisolated from diarrheal patients in Bangladesh
Authors: Rib Noshin Ibnat , Shams Fariza , Hossain Sakib Abrar , Sadique Abdus , Alam Jahidul , Debnath Pronoy , Hossain Arman , Rahman Aura , Tabassum Syeda Naushin , Huq Tahrima Saiha , Hossain Maqsud
Published: July 2024

This study marks the first identification and genomic characterization ofComamonas kerstersiiisolates from diarrheal patients in Bangladesh. C. kerstersiiis a gram-negative opportunistic bacterium which has also been reported in several clinical samples, including urine, blood, stool, peritoneal liquid, sputum. We carried out the whole genome sequencing of threeC. kerstersiiisolates for the first time in Bangladesh with an aim to analyze genomic features in 3 different strains isolated from Bangladesh. Seven AMR genes, aph(6)-Id, aph(3’’)-Ib, mph(E), mph(F), msr(E), sul2, and tet(A), have been observed in all the strains. We identified several virulence factors including copper homeostasis genes, type IV pili and type VI secretion system. phage regions and IncQ1 plasmid were also detected.
Enhancing Automated Medical Coding: Evaluating Embedding Models for ICD-10-CM Code Mapping
Authors: Klotzman Vanessa
Published: July 2024

Purpose

The goal of this study is to enhance automated medical coding (AMC) by evaluating the effectiveness of modern embedding models in capturing semantic similarity and improving the retrieval process for ICD-10-CM code mapping. Achieving consistent and accurate medical coding practices is crucial for effective healthcare management.

Methods

We compared the performance of embedding models, including text-embedding-3-large, text-embedding-004, voyage-large-2-instruct, and mistralembed, against ClinicalBERT. These models were assessed for their ability to capture semantic similarity between long and short ICD-10-CM descriptions and to improve the retrieval process for mapping diagnosis strings from the eICU database to the correct ICD-10-CM codes.

Results

The text-embedding-3-large and text-embedding-004 models outperformed ClinicalBERT in capturing semantic similarity, with text-embedding-3-large achieving the highest accuracy. For ICD-10 code retrieval, the voyage-large-2-instruct model demonstrated the best performance. Using the 15 nearest neighbors provided the best results. Increasing the number beyond this did not improve accuracy due to a lack of meaningful information.

Conclusion

Modern embedding models significantly outperform specialized models like ClinicalBERT in AMC tasks. These findings underscore the potential of these models to enhance medical coding practices, in spite of the challenges with ambiguous diagnosis descriptions.
The Efficacy and Safety of Pembrolizumab, Ipilimumab, and Nivolumab Monoteraphy and Combination for Colorectal Cancer: A Systematic Review and Meta-Analysis
Authors: Adrianto Albertus Ari , Riwanto Ignatius , Sadhana Udadi , Paramita Dewi Kartikawati , Setyawan Henry , Tjandra Kevin Christian , Respati Danendra Rakha Putra , Rampengan Derren David Christian Homenta , Ramadhan Roy Novri , Jangkang Gastin Gabriel , Mahati Endang
Published: July 2024

Background

Colorectal cancer (CRC) ranks third globally in cancer-related mortality, with rising incidence, particularly in Asia, projecting a 60% surge by 2030. Metastatic CRC (mCRC) presents a significant challenge with a grim 5-year survival rate of 14%. Emerging evidence suggests that tumors with DNA mismatch repair deficiency (dMMR) and high microsatellite instability (MSI-H) respond well to immune checkpoint inhibitors (ICIs), marking a paradigm shift in therapeutic approaches. This systematic review and meta-analysis aim to comprehensively assess Pembrolizumab, Nivolumab, and the combination of Nivolumab and Ipilimumab in advanced CRC, considering their significant antitumor efficacy in MSI-H/dMMR mCRC.

Methods

Following PRISMA guidelines and Cochrane Handbook standards, this study covers 2014 to 2024, involving advanced CRC patients treated with ICIs. A comprehensive literature search employed 12 independent authors across eight databases. Parameters such as overall survival, progression-free survival, and objective response rate were extracted.The Cochrane Collaboration’s Risk of Bias version 2 tool assessed risk. Statistical analysis utilized mean difference and risk ratios with random-effect models due to anticipated heterogeneity. Robustness was ensured through publication bias analysis and sensitivity meta-analysis. Linear regression explored associations in subgroup analysis.

Results

The meta-analysis evaluated ORR and OS across different immunotherapy interventions. Nivolumab, Nivolumab+Ipilimumab, and Pembrolizumab exhibited varying ORR and OS effect sizes with corresponding heterogeneity levels. Progression-free survival (PFS) analysis also showed diverse effect sizes and heterogeneity levels across the three interventions. The study provides a comprehensive overview of response rates and survival outcomes for these immunotherapies in advanced CRC.

Conclusions

The study concludes that combination immunotherapy, particularly Nivolumab and Ipilimumab, presents a promising avenue for advanced CRC treatment, showing superior efficacy. Pembrolizumab monotherapy also exhibited promise. While the study offers valuable insights, the identified heterogeneity emphasizes the need for additional research. Adverse effects were generally low, supporting the viability of the studied immunotherapies. The study acknowledges limitations and calls for ongoing investigation to refine and validate these findings, marking a pioneering effort in systematically comparing short-term and long-term effects of anti-CTLA-4 and anti-PD-1 therapies in CRC.
Posttraumatic stress-related white matter microstructure alterations and chronic pain
Authors: Quidé Yann , Kamarul Khaizuran , Gustin Sylvia M
Published: July 2024

Background. Posttraumatic stress symptoms (PTSS) are commonly experienced in people with chronic pain. Reduced white matter microstructural integrity in the uncinate fasciculus and the cingulum has been reported similarly in chronic pain and PTSD studies separately. However, the relationship between chronic pain, PTSS and white matter integrity remains unclear. Methods. Thirty-six subjects with and 20 without chronic pain (controls) underwent diffusion weighted imaging and completed the civilian version of the Posttraumatic stress Disorder CheckList (PCL-C). Average fractional anisotropy (FA) and mean diffusivity (MD) values were extracted from three regions-of-interest (uncinate fasciculus, cingulate and hippocampal portions of the cingulum). A series of multiple linear regressions determined the main effects of Group, PTSS severity (PCL-C total score) and their interactions on each ROI separately. Results. The group-by-PTSS interaction was significantly associated with variations of uncinate fasciculus FA. Moderation analysis indicated that increasing PTSS severity was significantly associated with reduced uncinate fasciculus FA in the control group, but not in chronic pain group. No other significant association was found for any other ROI FA values, and there was no significant association with MD values. Conclusions. Consistent with previous studies, increasing PTSS levels were associated with reduced FA of the uncinate fasciculus in controls, but not in people with chronic pain. This suggests that different mechanisms may be at play in chronic pain, including the interplay with other psychopathological problems, such as depression and anxiety. Future larger studies of more homogeneous chronic pain conditions are warranted.
Enhanced purinergic signaling in the paraventricular hypothalamus induces hyperphagic obesity and insulin resistance
Authors: Liu Yu , Zhang Haiyang , Zhang Qian , Najam Syeda Sadia , Liang Xian , Sirakawin Chaweewan , Lin Dongfa , Huang Shangyuan , Bondarenko Anastasiia , Konopka Witold , Zhang Yi , Zhang Zhi , Wu Shihao , Jing Miao , Vinnikov Ilya A.
Published: July 2024

Body energy homeostasis is tightly regulated by hypothalamic neural circuits. However, their remodeling upon metabolic stress remains incompletely characterized, translating to unprecedented challenges to develop safe medications against the surge of metabolic diseases. Oxytocin (OXT) neurons in the paraventricular nucleus of the hypothalamus (PVH) are one of the key appetite-suppressing effectors within the melanocortin system. In this work, we report that metabolic stress in mice evokes spatiotemporally selective ATP release (Inflares) from PVH astrocytes, accompanied with the expression of hematopoietic lineage-specific ADP/ATP receptor P2Y12on OXT (PVHOXT) neurons. Importantly, “ectopic” emergence of P2Y12on OXT neurons of patients with diabetes mellitus suggests an evolutionary conserved purinergic response to metabolic stress. Strikingly, increased purinergic signaling leads to impaired responsiveness of PVHOXTneurons accompanied with hyperphagic obesity and insulin resistance in mice. Moreover, nasal administration of clinically approved doses of P2Y12inhibitors counteracts diet-induced obesity and insulin resistance in mice and spontaneous weight gain in monkeys, paving the way for application of these compounds in patients with metabolic disorders.
Single-cell transcriptomics highlights sexual cues among reproductive life stages of uncultivated Acantharia (Radiolaria)
Authors: Rizos Iris , Romac Sarah , Juery Caroline , Berthelier Charlotte , Decelle Johan , Bernardes Juliana , Corre Erwan , Bittner Lucie , Not Fabrice
Published: July 2024

As an innate property of life, the ability to reproduce is a key process for the perpetuation of organisms. Along the evolution of protist reproductive strategies, the molecular machinery of sexual recombination is estimated to have been inherited from the last eukaryotic common ancestor (LECA). Nevertheless, unraveling the sexual cycles of extant free-living protist lineages remains challenging, given the enigmatic roles of many uncultivated life stages. Among the uncultivated planktonic group of Acantharia (Radiolaria), a hypothetical sexual cycle has been proposed since the late 19th century, including the existence of a gamete-like life stage of undetermined ploidy, referred to as swarmers. In order to investigate the sexual nature of acantharian reproductive stages, we conducted single-cell transcriptomic analysis across various acantharian life stages. Our results show distinct functional profiles for reproductive and vegetative life stages, while revealing the expression of the reference eukaryotic genes involved in gamete fusion, HAP2/GCS1 and GEX1-KAR5, in swarmers and pre-swarmer stages. Annotation of differentially expressed life stage-specific genes, also highlights putative meiosis-related functions among swarmers, while suggesting the existence of a potential swarmer/vegetative intermediate stage expressing putative growth-related genes. This original life stage-specific genetic data is coherent with morphological evidence supporting the existence of an acantharian sexual cycle, with swarmers acting as gametes. Moreover, it paves the way for a deeper understanding of radiolarian cell biology and ecology at a single-cell scale.

Highlights

Acantharia demonstrate both morphological and genetic evidence of a sexual cycle

Acantharian reproductive stages are enriched in functions related to cell division

Nuclear fusion gene family GEX1-KAR5 is up-regulated in putative acantharian gametes

Most expressed genes specific to acantharian reproductive stages are unassigned

Reproduction-specific unassigned genes include putative sex-related functions
Exploring glioma heterogeneity through omics networks: from gene network discovery to causal insights and patient stratification
Authors: Kastendiek Nina , Coletti Roberta , Gross Thilo , Lopes Marta B.
Published: July 2024

Gliomas are primary malignant brain tumors with a typically poor prognosis, exhibiting significant heterogeneity across different cancer types. Each glioma type possesses distinct molecular characteristics determining patient prognosis and therapeutic options. This study aims to explore the molecular complexity of gliomas at the transcriptome level, employing a comprehensive approach grounded in network discovery. The graphical lasso method was used to estimate a gene co-expression network for each glioma type from a transcriptomics dataset. Causality was subsequently inferred from correlation networks by estimating the Jacobian matrix. The networks were then analyzed for gene importance using centrality measures and modularity detection, leading to the selection of genes that might play an important role in the disease. Spectral clustering based on patient similarity networks was applied to stratify patients into groups with similar molecular characteristics and to assess whether the resulting clusters align with the diagnosed glioma type. The results presented highlight the ability of the proposed methodology to uncover relevant genes associated with glioma intertumoral heterogeneity. Further investigation might encompass biological validation of the putative biomarkers disclosed.
Protease shaving ofMycobacterium tuberculosisfacilitates vaccine antigen discovery and delivery of novel cargoes to the Mtb surface
Authors: Lepe Bianca A. , Zheng Christine R. , Leddy Owen K. , Allsup Benjamin L. , Solomon Sydney L. , Bryson Bryan D.
Published: July 2024

Tuberculosis (TB), caused byMycobacterium tuberculosis(Mtb), is the leading cause of infectious disease death and lacks a vaccine capable of protecting adults from pulmonary TB. Studies have shown that Mtb uses a variety of mechanisms to evade host immunity. Secreted Mtb proteins such as Type VII secretion system substrates have been characterized for their ability to modulate anti-Mtb immunity; however, studies of other pathogens such asSalmonellaTyphi andStaphylococcus aureushave revealed that outer membrane proteins can also interact with the innate and adaptive immune system. The Mtb outer membrane proteome has received relatively less attention due to limited techniques available to interrogate this compartment. We filled this gap by deploying protease shaving and quantitative mass spectrometry to identify Mtb outer membrane proteins which serve as nodes in the Mtb-host interaction network. These analyses revealed several novel Mtb proteins on the Mtb surface largely derived from the PE/PPE class of Mtb proteins, including PPE18, a component of a leading Mtb vaccine candidate. We next exploited the localization of PPE18 to decorate the Mtb surface with heterologous proteins and deliver these surface-engineered Mtb to the phagosome. Together, these studies reveal potential novel targets for new Mtb vaccines as well as facilitate new approaches to study difficult to study cellular compartments during infection.
Progerin Can Induce DNA Damage in the Absence of Global Changes in Replication or Cell Proliferation
Authors: Joudeh Liza A. , Schuck P. Logan , Van Nina M. , DiCintio Alannah J. , Stewart Jason A. , Waldman Alan S.
Published: July 2024

Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare genetic condition characterized by features of accelerated aging, and individuals with HGPS seldom live beyond their mid-teens. The syndrome is commonly caused by a point mutation in the LMNA gene which codes for lamin A and its splice variant lamin C, components of the nuclear lamina. The mutation causing HGPS leads to production of a truncated, farnesylated form of lamin A referred to as “progerin.” Progerin is also expressed at low levels in healthy individuals and appears to play a role in normal aging. HGPS is associated with an accumulation of genomic DNA double-strand breaks (DSBs) and alterations in the nature of DSB repair. The source of DSBs in HGPS is often attributed to stalling and subsequent collapse of replication forks in conjunction with faulty recruitment of repair factors to damage sites. In this work, we used a model system involving immortalized human cell lines to investigate progerin-induced genomic damage. Using an immunofluorescence approach to visualize phosphorylated histone H2AX foci which mark sites of genomic damage, we report that cells engineered to express progerin displayed a significant elevation of endogenous damage in the absence of any change in the cell cycle profile or doubling time of cells. Genomic damage was enhanced and persistent in progerin-expressing cells treated with hydroxyurea. Overexpression of wild-type lamin A did not elicit the outcomes associated with progerin expression. Our results show that DNA damage caused by progerin can occur independently from global changes in replication or cell proliferation.
Optimizing Multi-Environment Trials in The US Rice Belt via Smart-Climate-Soil Prediction Based-Models and Economic Importance
Authors: Prado Melina , Famoso Adam , Guidry Kurt , Fritsche-Neto Roberto
Published: July 2024

Rice breeding programs globally have worked to release increasingly productive and climate-smart cultivars, but the genetic gains have been limited for some reasons. One is the capacity for field phenotyping, which presents elevated costs and an unclear approach to defining the number and allocation of multi-environmental trials (MET). To address this challenge, we used soil information and ten years of historical weather data from the USA rice belt, which was translated into rice response based on the rice cardinal temperatures and crop stages. Next, we eliminated those highly correlated Environmental Covariates (ECs) (>0.95) and applied a supervised algorithm for feature selection using two years of data (2021-22) and 25 genotypes evaluated for grain yield in 18 representative locations in the Southern USA. To test the trials’ optimization, we performed the joint analysis using prediction-based models in four different scenarios: I) considering trials as non-related, ii) including the environmental relationship matrix calculated from ECs, iii) within clusters; iv) sampling one location per cluster. Finally, we weigh the trial’s allocation considering the counties’ economic importance and the environmental group to which they belong. Our findings show that eight ECs explained 58% of grain yield variation across sites and 53% of the observed GxE. Moreover, it is possible to reduce 28% the number of locations without significant loss in accuracy. Furthermore, the US Rice belt comprises four clusters, with economic importance varying from 13 to 45%. These results will help us better allocate trials in advance and reduce costs without penalizing accuracy.
Neutrino
CP
measurement in the presence of RG running with mismatched momentum transfers
Authors: Ge Shao-Feng , Kong Chui-Fan , Pasquini Pedro
Published: July 2024

The neutrino mixing parameters are expected to have renormalization group (RG) running effect in the presence of new physics. If the momentum transfers at production and detection mismatch with each other, the oscillation probabilities are generally modified and become dependent on not just the neutrino energy but also the momentum transfer. Even in the limit of vanishing baseline, the transition probability for the appearance channel is interestingly not zero. This would significantly affect the sensitivity of the genuine leptonic Dirac CP phase. We further explore the possibility of combining the long- and short-baseline neutrino experiments to constrain such RG running effect for the purpose of guaranteeing the CP measurement. To simulate the double dependence on the neutrino energy and momentum transfer, we extend the usual o simulation of fixed baseline experiments and use a two-dimensional χ2 analysis to obtain sensitivities.

Published by the American Physical Society
2024
Revisiting formation of primordial black holes in a supercooled first-order phase transition
Authors: Flores Marcos M. , Kusenko Alexander , Sasaki Misao
Published: July 2024

We reexamine production of primordial black holes in a supercooled phase transition. While a mere overdensity associated with a surviving false-vacuum patch does not imply formation of a black hole, it is possible for such a patch to evolve and create a black hole, thanks to the gradient energy stored in the bubble wall.

Published by the American Physical Society
2024
TT¯
deformation of
N=(1,1)
off-shell supersymmetry and partially broken supersymmetry
Authors: Lee Kyung-Sun , Yoon Junggi
Published: July 2024

We construct the superaction for the TT¯ deformation of 2D free N=(1,1) supersymmetric model with a deformed superfield. We show that the N=(1,1) off-shell supersymmetry in the free theory is deformed under the TT¯ deformation, which is incorporated in the deformed superfield. We interpret this superaction as an effective action of the Goldstone superfield for the partial spontaneous breaking of N=(2,2) supersymmetry to N=(1,1). We show that the unbroken and broken supersymmetry of the effective superaction corresponds to the off-shell N=(1,1) supersymmetry and the off-shell Fermi global nonlinear symmetry in the TT¯-deformed theory, respectively. We demonstrate that this effective superaction can be obtained by the nonlinear realization of the partially broken global supersymmetry (PBGS) from the coset superspace. Furthermore, we reproduce the superaction by the constrained superfield method accompanied by a field redefinition.

Published by the American Physical Society
2024
Ring formation of transition metal trichalcogenide TaSe3 using vapor liquid process
Authors: Tsubota Masakatsu , Watanabe Masahito
Published: July 2024

The synthesis of TaSe3 ring-shaped crystals displaying the coffee ring effect is investigated. By recrystallizing TaSe3 microcrystals dissolved in droplets of condensed Se gas, ring-shaped crystals were successfully grown. This novel method for ring formation effectively addressed the issue of connecting the edges of the crystal. Consequently, the synthesis method has the capability to grow MX
3 ring-shaped crystals in any location where droplets can condense, can now be grown in specific locations, thus creating opportunities for advancements in electronic component development.
Synthesis and evaluation of Schiff base as corrosion inhibitor for carbon steel in 1 M HCl solution
Authors: Jafari Hojat , Ameri Elham
Published: July 2024

Purpose

The main purpose of the present study is to introduce new Schiff bases as corrosion inhibitor for carbon steel in 1 M HCl. The inhibitory activity of Schiff base was also assessed.

Design/methodology/approach

2,2′-((1Z,1′Z)-((2,2-dimethylpropane-1,3-diyl)bis(azanylylidene))bis(methanylylidene))diphenol was synthesized and it’s performance as an inhibitor was then investigated in 1 M HCl. The inhibition of this compound was studied and evaluated by the chemical methods of electrochemical impedance spectroscopy, electrochemical potential dynamic polarization and Atomic Force microscopy (AFM) method. The thermodynamics parameters were investigated for corrosion of carbon steel in both the absence and presence of Schiff base.

Findings

The results of the tests showed that this compound has a good performance as an inhibitor and the percentage of inhibition on steel corrosion will increase with increasing concentration and it will reach 70% in the presence of 2 × 10−3 M of this inhibitor. Polarization tests indicated that this compound will act as a mixed inhibitor. Nyquist curves showed that the addition of this substance to the solution increased the charge transfer resistance and decreased the capacity of the double layer. The absorption of the new Schiff base on steel follows Langmuir adsorption isotherm, and the amount of free energy of adsorption indicates the spontaneous adsorption of this inhibitor. Using AFM investigations, the results of electrochemical methods were confirmed.

Originality/value

Incorporation of a new Schiff base into 1 M HCl is a promising approach for protecting the carbon steel against corrosive solution.