bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence of both molecular cloud and fluid chemistry in Ryugu regolith
Authors: Bose Maitrayee , Root Robert A. , Guan Yunbin , Eaton Jacob , Wittmann Axel , Skrmetti Thomas , Desch Steven J.
Published: July 2024

The sulfur chemistry of (162173) Ryugu particles can be a powerful tracer of molecular cloud chemistry and small body processes, but it has not been well explored. We report identification of organosulfurs and a sulfate grain in two Ryugu particles, A0070 and A0093. The sulfate grain shows oxygen isotope ratios (δ
17
O = −11.0 ± 4.3 per mil, δ
18
O = −7.8 ± 2.3 per mil) that are akin to silicates in Ryugu but exhibit mass-independent sulfur isotopic fractionation (Δ
33
S = +5 ± 2 per mil). A methionine-like coating on the sulfate grain is isotopically anomalous (δ
15
N = +62 ± 2 per mil). Both the sulfate and organosulfurs can simultaneously form and survive during aqueous alteration within Ryugu’s parent body, under reduced conditions, low temperature, and a pH >7 in the presence of N-rich organic molecules. This work extends the heliocentric zone where anomalous sulfur, formed by selective photodissociation of H
2
S gas in the molecular cloud, is found.
Discovery of the final primitive Frank-Kasper phase of clathrate hydrates
Authors: Muromachi Sanehiro , Takeya Satoshi
Published: July 2024

In weakly bound materials such as water, one of the three primitive Frank-Kasper (FK) phases, the Z phase, is long absent due to the relatively unstable framework. The Z phase in clathrate hydrate, which is known as the HS-I structure, has now been found by precise tuning of the molecular guest structure. In the crystal structure, the never stabilized combination water cage of two 15-hedra and two 14-hedra formed with its original symmetries, providing sufficient gas capacity to the 12-hedral cages. With the discovery of the final FK clathrate hydrate, guest design now enables engineering of weak interactions in any mix of the three, illuminating how to leverage properties of clathrates in the broadest sense.
Multimodal soft valve enables physical responsiveness for preemptive resilience of soft robots
Authors: Pontin Marco , Damian Dana D.
Published: July 2024

Resilience is crucial for the self-preservation of biological systems: Humans recover from wounds thanks to an immune system that autonomously enacts a multistage response to promote healing. Similar passive mechanisms can enable pneumatic soft robots to overcome common faults such as bursts originating from punctures or overpressurization. Recent technological advancements, ranging from fault-tolerant controllers for robot reconfigurability to self-healing materials, have paved the way for robot resilience. However, these techniques require powerful processors and large datasets or external hardware. How to extend the operational life span of damaged soft robots with minimal computational and physical resources remains unclear. In this study, we demonstrated a multimodal pneumatic soft valve capable of passive resilient reactions, triggered by faults, to prevent or isolate damage in soft robots. In its forward operation mode, the valve, requiring a single supply pressure, isolated punctured soft inflatable elements from the rest of the soft robot in as fast as 21 milliseconds. In its reverse operation mode, the valve can passively protect robots against overpressurization caused by external disturbances, avoiding plastic deformations and bursts. Furthermore, the two modes combined enabled the creation of an endogenously controlled valve capable of autonomous burst isolation. We demonstrated the passive and quick response and the possibility of monolithic integration of the soft valve in grippers and crawling robots. The approach proposed in this study provides a distributed small-footprint alternative to controller-based resilience and is expected to help soft robots achieve uninterrupted long-lasting operation.
Web-based distributed robot localization
Authors: Matsiko Amos
Published: July 2024

Web-based strategy enables robots to communicate estimated locations among robot peers.
Senataxin mediates R-loop resolution on HPV episomes
Authors: Jose Leny , Smith Keely , Crowner Anaiya , Androphy Elliot J. , DeSmet Marsha
Published: July 2024

Three-stranded DNA–RNA structures known as R-loops that form during papillomavirus transcription can cause transcription–replication conflicts and lead to DNA damage. We found that R-loops accumulated at the viral early promoter in human papillomavirus (HPV) episomal cells but were greatly reduced in cells with integrated HPV genomes. RNA–DNA helicases unwind R-loops and allow for transcription and replication to proceed. Depletion of the RNA–DNA helicase senataxin (SETX) using siRNAs increased the presence of R-loops at the viral early promoter in HPV-31 (CIN612) and HPV-16 (W12) episomal HPV cell lines. Depletion of SETX reduced viral transcripts in episomal HPV cell lines. The viral E2 protein, which binds with high affinity to specific palindromes near the promoter and origin, complexes with SETX, and both SETX and E2 are present at the viral p97 promoter in CIN612 and W12 cells. SETX overexpression increased E2 transcription activity on the p97 promoter. SETX depletion also significantly increased integration of viral genomes in CIN612 cells. Our results demonstrate that SETX resolves viral R-loops to proceed with HPV transcription and prevent genome integration.

IMPORTANCE

Papillomaviruses contain small circular genomes of approximately 8 kilobase pairs and undergo unidirectional transcription from the sense strand of the viral genome. Co-transcriptional R-loops were recently reported to be present at high levels in cells that maintain episomal HPV and were also detected at the early viral promoter. R-loops can inhibit transcription and DNA replication. The process that removes R-loops from the PV genome and the requisite enzymes are unknown. We propose a model in which the host RNA–DNA helicase senataxin assembles on the HPV genome to resolve R-loops in order to maintain the episomal status of the viral genome.
Supplemental Material: Pre-Himalayan tectono-metamorphic impresses in the Baijnath klippe, Kumaun Himalaya, NW India: Implications of a veiled saga of Paleoproterozoic–Neoproterozoic crustal evolution and thermal history of the northern Indian cratonic margin
Authors: Mukherjee Sneha , al. et
Published: July 2024

Figure S1: Geological map of the Baijnath klippe showing the sample position used for petrological, geochemical, and geochronological study. Figure S2: Ti-versus-XMg plot of Ti-in-biotite of two textural modes. Figure S3: Wetherill plots of U-Pb zircon data for each sample: (A) mylonitic granitoids, (B) less-deformed granitoids, and (C) supracrustal rocks. Table S1: Representative mineral chemical data analyzed by EPMA from the samples of Baijnath supracrustals. Table S2: Mineral compositional data of amphibole along the Hbl-Bt profile. Table S3: Representative major and trace element data with CIPW norm data from the Baijnath granitoids. Table S4: Zircon U-Pb (LA-ICP-MS) data from the samples of the Baijnath klippe. Table S5: Apatite U-Pb (LA-ICP-MS) data from the samples of the Baijnath supracrustals. Table S6: Representative Ti-in-zircon, Ti-in-quartz thermometric data and pressure estimation data for the granitoids. Table S7: General description, modal abundance of the supracrustal samples used in this work.
Safety and adherence to medications and self-care advice in oncology (SAMSON): pilot randomised controlled trial protocol
Authors: Dang Thu Ha , Wickramasinghe Nilmini , Jayaraman Prem Prakash , Burbury Kate , Alexander Marliese , Whitechurch Ashley , Quinn Steve , Rowan Gail , Brooks Sally L , Schofield Penelope
Published: July 2024

Introduction

With the increasing use of oral anti-cancer medicines (OAMs), research demonstrating the magnitude of the medication non-adherence problem and its consequences on treatments’ efficacy and toxicity is drawing more attention. Mobile phone interventions may be a practical solution to support patients taking OAMs at home, yet evidence to inform the efficacy of these interventions is lacking. The safety and adherence to medications and self-care advice in oncology (SAMSON) pilot randomised control trial (RCT) aims to evaluate the acceptability, feasibility and potential efficacy of a novel digital solution to improve medication adherence (MA) among people with cancer.

Methods and analysis

This is a two-arm, 12-week, pilot RCT aiming to enrol 50 adults with haematological, lung or melanoma cancers at an Australian metropolitan specialised oncology hospital, who are taking oral anti-cancer medicines. Participants will be randomised (1:1 allocation ratio) to either the intervention group (SAMSON solution) or the control group (usual care). The primary outcomes are the acceptability and feasibility of SAMSON. The secondary outcomes are MA, toxicity self-management, anxiety and depressive symptoms, health-related quality of life, and parameters relating to optimal intervention strategy. Quantitative data will be analysed on a modified intention-to-treat basis.

While multicomponent interventions are increasingly introduced, SAMSON incorporates novel approaches to the solution. SAMSON provides a comprehensive, patient-centred, digital MA intervention solution with seamless integration of a mobile platform with clinical consultations that are evidence-based, theory-based, co-designed and rigorously tested. The pilot trial will determine whether this type of intervention is feasible and acceptable in oncology and will provide a foundation for a future full-scale RCT.

Ethics and dissemination

Primary ethics approvals were received from Peter MacCallum Cancer Centre and Swinburne University of Technology Human Research Ethics Committees (HREC/95332/PMCC and 20237273–15836). Results will be disseminated via peer-reviewed publications and presentations at international and national conferences.

Trial registration number

The protocol has been prospectively registered on the Australian New Zealand Clinical Trials Registry with trial registration number (ACTRN12623000472673).
Sodium valproate is associated with cortical thinning of disease-specific areas in juvenile myoclonic epilepsy
Authors: Crespo Pimentel Bernardo , Kuchukhidze Giorgi , Xiao Fenglai , Caciagli Lorenzo , Höfler Julia , Rainer Lucas , Kronbichler Martin , Vollmar Christian , Duncan John S , Trinka Eugen , Koepp Matthias , Wandschneider Britta
Published: July 2024

Background

Juvenile myoclonic epilepsy (JME) is associated with cortical thinning of the motor areas. The relative contribution of antiseizure medication to cortical thickness is unknown. We aimed to investigate how valproate influences the cortical morphology of JME.

Methods

In this cross-sectional study, individuals with JME with and without valproate, with temporal lobe epilepsy (TLE) with valproate and controls were selected through propensity score matching. Participants underwent T1-weighted brain imaging and vertex-wise calculation of cortical thickness.

Results

We matched 36 individuals with JME on valproate with 36 individuals with JME without valproate, 36 controls and 19 individuals with TLE on valproate. JME on valproate showed thinning of the precentral gyri (left and right, p<0.001) compared with controls and thinning of the left precentral gyrus when compared with JME not on valproate (p<0.01) or to TLE on valproate (p<0.001). Valproate dose correlated negatively with the thickness of the precentral gyri, postcentral gyri and superior frontal gyrus in JME (left and right p<0.0001), but not in TLE.

Conclusions

Valproate was associated with JME-specific and dose-dependent thinning of the cortical motor regions. This suggests that valproate is a key modulator of cortical morphology in JME, an effect that may underlie its high efficacy in this syndrome.
Quantifying the effectiveness of an active treatment in improving highway-railway grade crossing safety in Canada: an empirical Bayes observational before–after study
Authors: Shangguan Qiangqiang , Wang Yubo , Fu Liping
Published: July 2024

Transportation engineers face challenging safety investment decisions, particularly for highway-railway grade crossings (HRGCs), where rare collision occurrences and incomplete historical records complicate the assessment of countermeasure cost-effectiveness. This study introduces an empirical Bayes (EB) observational before–after approach to address these challenges, specifically examining the impact of a widely used safety countermeasure: flashing lights, bells, and gates (FLBG). The research covers a total 171 FLBG crossings with pre-implementation conditions varying between standard reflective crossing signs and flashing lights and bells, utilizing collision data from 2000 to 2012 for analysis. This study is the first to substantiate quantitatively the effectiveness of FLBG treatment in improvising the safety of HRGCs and show that the effect is dependent of crossing characteristics, such as track angle, pavement conditions, and train speed limits. These findings can provide valuable support to decision-makers, enabling them to make more effective decisions for grade crossing safety improvement projects.
Seabird inputs drive changes in Cladocera assemblages in freshwater ponds
Authors: Kane Zoe A. , Duda Matthew P. , Simmatis Brigitte , Smol John P.
Published: July 2024

Seabirds are biovectors that transport large concentrations of nutrients from their marine feeding areas to terrestrial breeding grounds. Here, we used subfossil cladoceran assemblages to assess if, and how, changes in the world’s largest colony of Leach’s Storm-Petrels affected the structure of Cladocera assemblages over the past ∼1700 years. Using sediment cores from four ponds impacted by Leach’s Storm-Petrel colonies on Baccalieu Island (NL, Canada), we observed a consistent transition in cladoceran assemblages from benthic/littoral to pelagic taxa in association with high seabird presence. This shift aligns with previously published limnological changes that tracked the growth of the colony. Compared to trends in sedimentary chlorophyll- a, pelagic cladoceran taxa lagged behind algal shifts driven by seabird activity. The main drivers of cladoceran assemblage shifts were likely alterations to the physical habitat structure and food availability driven by seabird inputs. Furthermore, deposition of calcium from seabirds may have also contributed to changing the composition of cladoceran communities. Our study provides information on food web shifts associated with seabird-driven eutrophication, which can be compared to future paleoecological studies.
Self-service technologies: A bibliometric analysis
Authors: Thakral Shruti , Kamra Vishal
Published: July 2024

In this paper, we applied bibliometric methods to analyze the field of self-service technology (SST). Our goal was to identify the most impactful publications and journals, comprehend the key topics studied as well as the emerging trends and forecast future research trends in this domain. The Scopus database was used to extract 490 documents related to SST between 2000 and 2023. Our analyses include the most cited papers, sources of publications, bibliographic coupling, and topic modeling. As the body of literature continues to expand, we identified the most influential source “Journal of Service Marketing” which holds a prominent position in this area. The citation analysis revealed the highly influential papers that have made significant contributions to their respective fields. Notably, Meuter [Meuter, ML, AL Ostrom, RI Roundtree and MJ Bitner (2000). Self-Service Technologies: Understanding Customer Satisfaction with Technology-Based Service Encounters] in the realm of SST emerged as the most frequently cited paper, exerting substantial influence in academic literature. We applied bibliometric coupling in this field, which resulted in the discovery of seven clusters in SST. These clusters shed light on various aspects associated with these topics, offering valuable insights. The findings of this research offer valuable insights to study researchers by bringing clarity to this research field. Finally, the study presents the implications and recommendations for researchers. The findings of this paper offer valuable insights to study researchers by bringing clarity to the fields of the study.
Reproducibility Report for the Paper "Performance Evaluation of Spintronic-Based Spiking Neural Networks Using Parallel Discrete-Event Simulation"
Authors: Ruscheinski Andreas
Published: July 2024

The examined paper introduces
Doryta
, a simulator for Spiking Neural Networks implemented as a ROSS model.

The software artifact is available as part of the paper’s supplemental material and can be accessed via the journal’s website. It is well documented and enhances the overall quality of the paper by providing access to the source code of the Doryta simulator and necessary scripts to reproduce the results shown in the figure. Using the script, we reproduced all major results presented in the paper.

Thus, the paper qualifies for the
Artifact Available
, the
Artifact Evaluated–Reusable
, and the
Artifact Validated–Results Reproduced
badges.
Corrosion of Lithium-ion Battery Cylindrical Cell Hardware: Understanding the Mechanisms and Exploring Effective Solutions
Authors: Stoševski Ivan , Bonakdarpour Arman , Smith Scott R. , Jacobs Allan , Way Brian , Wilkinson David P.
Published: July 2024

We present a detailed examination of Ni corrosion in lithium-ion battery Ni-coated steel cylindrical cell hardware, focusing on LiPF6-based electrolytes contaminated with water. The corrosion potential of the cell hardware is predominantly controlled by the iron component of the cylindrical can which cathodically protects the Ni coating. Despite the presence of cathodic protection, the Ni coating still experiences significant crevice corrosion, as confirmed through chemical aging tests. Mechanistic investigations on pure Ni metal reveal two distinct corrosion pathways depending on the presence or absence of oxygen in the electrolyte. The pathway involving oxygen proves to be more detrimental, as it oxidizes Ni in conjunction with acid, leading to the generation of water and the regeneration of corrosive species. This pathway exhibits corrosion rates two orders of magnitude higher than the alternative pathway. The dissolved Ni species predominantly exist in the +2 oxidation state and forms highly soluble F-rich compounds, comprising a mixture of associated species denoted by the formula Ni(PxOyFz)w. Finally, several suggestions for effectively mitigating Ni corrosion have been proposed, with alloying with chromium being the most effective.
Analysis of the Stability and Chaotic Dynamics of an Ecological Model
Authors: Abbasi Muhammad Aqib , Din Qamar , Albalawi Olayan , Niaz Rizwan , Alomair Mohammed Ahmed , Alomair Abdullah Mohammed
Published: July 2024

Modelling has become an eminent tool in the study of ecological systems. Ecological modelling can help implement sustainable development, mathematical models, and system analysis that explain how ecological processes can promote the sustainable management of resources. In this paper, we also chose a four‐dimensional discrete‐time Lotka–Volterra ecological model and analyzed its dynamic behavior. In particular, we derived the parametric conditions for the existence of biologically feasible solutions and the stability of the fixed points. We also provided graphs to study the spectrum behavior of all fixed points. In addition, we have seen that when the intrinsic dynamics of the population exceed a certain threshold, the system bifurcates. This particular range of inherent population dynamics depends on the values of other biological parameters and the initial population. We proved that the instability of the model resulted in Neimark–Sacker and period‐doubling bifurcations. To confirm these two types of bifurcation, we used bifurcation theory, and to find the direction of bifurcation, we used graphical results. Mainly, through novel periodic plots, we confirm the coexistence of the population and the possible equilibrium states. We apply Marotto’s theorem to verify the existence of chaos in the system. To control the chaos, we use a hybrid control feedback methodology. Finally, we provide numerical examples to illustrate our theoretical results. The outcomes of the numerical simulations show chaotic long‐term behavior across an extensive range of parameters.
Exploring the Analgesic Initiation Mechanism of Tuina in the Dorsal Root Ganglion of Minor CCI Rats via the TRPV1/TRPA1‐cGMP Pathway
Authors: Yang Zhenjie , Sa Chula , Yu Tianyuan , Chen Jinping , Zhang Runlong , Zhang Yingqi , Liu Jiayue , Zhang Hanyu , Sun Jiawei
Published: July 2024

Tuina is a treatment method in traditional Chinese medicine which has analgesic effects and effectively alleviates the symptoms of neuropathic pain (NP). Transient receptor potential vanilloid type 1 (TRPV1) and transient receptor potential ankyrin type 1 (TRPA1) play major roles in transmitting nociceptive sensory signals in the nociceptive primary sensory dorsal root ganglion (DRG) nerve. The nitric oxide (NO)/cyclic guanosine 3′,5′‐monophosphate(cGMP) pathway exerts both nociceptive and antinociceptive effects in various chronic pain models. TRPV1 and TRPA1 mediate the influx of calcium, which stimulates the generation of NO. Subsequently, NO activates the NO/cGMP/protein kinase G (PKG) signaling pathway, thereby improving hyperalgesia. In the present study, oa rat model of NP with minor chronic constriction injury (CCI) of the right sciatic nerve of NP was established. The results of behavioral testing showed that, after a one‐time tuina intervention, the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were prolonged to varying degrees in the tuina group compared with the model group. Similarly, the expression of TRPV1, TRPA1, NO, soluble guanylate cyclase β (sGCβ), cGMP, and PKG1 was significantly decreased in the DRG of the tuina and tuina + TRPV1/TRPA1 antagonist group was significantly decreased. These findings suggest that the tuina intervention can effectively improve the symptoms of thermal and mechanical allodynia caused by peripheral nerve injuries. Tuina exerts immediate analgesic effects through the TRPV1/TRPA1‐NO‐cGMP‐PKG signaling pathway.
Supplementary Video S1 from PDX-MI: Minimal Information for Patient-Derived Tumor Xenograft Models
Authors: Meehan Terrence F. , Conte Nathalie , Goldstein Theodore , Inghirami Giorgio , Murakami Mark A. , Brabetz Sebastian , Gu Zhiping , Wiser Jeffrey A. , Dunn Patrick , Begley Dale A. , Krupke Debra M. , Bertotti Andrea , Bruna Alejandra , Brush Matthew H. , Byrne Annette T. , Caldas Carlos , Christie Amanda L. , Clark Dominic A. , Dowst Heidi , Dry Jonathan R. , Doroshow James H. , Duchamp Olivier , Evrard Yvonne A. , Ferretti Stephane , Frese Kristopher K. , Goodwin Neal C. , Greenawalt Danielle , Haendel Melissa A. , Hermans Els , Houghton Peter J. , Jonkers Jos , Kemper Kristel , Khor Tin O. , Lewis Michael T. , Lloyd K.C. Kent , Mason Jeremy , Medico Enzo , Neuhauser Steven B. , Olson James M. , Peeper Daniel S. , Rueda Oscar M. , Seong Je Kyung , Trusolino Livio , Vinolo Emilie , Wechsler-Reya Robert J. , Weinstock David M. , Welm Alana , Weroha S. John , Amant Frédéric , Pfister Stefan M. , Kool Marcel , Parkinson Helen , Butte Atul J. , Bult Carol J.
Published: July 2024

A video describing PDX mice, minimal information, and why minimal information is needed in the PDX research field.
S1 from PDX-MI: Minimal Information for Patient-Derived Tumor Xenograft Models
Authors: Meehan Terrence F. , Conte Nathalie , Goldstein Theodore , Inghirami Giorgio , Murakami Mark A. , Brabetz Sebastian , Gu Zhiping , Wiser Jeffrey A. , Dunn Patrick , Begley Dale A. , Krupke Debra M. , Bertotti Andrea , Bruna Alejandra , Brush Matthew H. , Byrne Annette T. , Caldas Carlos , Christie Amanda L. , Clark Dominic A. , Dowst Heidi , Dry Jonathan R. , Doroshow James H. , Duchamp Olivier , Evrard Yvonne A. , Ferretti Stephane , Frese Kristopher K. , Goodwin Neal C. , Greenawalt Danielle , Haendel Melissa A. , Hermans Els , Houghton Peter J. , Jonkers Jos , Kemper Kristel , Khor Tin O. , Lewis Michael T. , Lloyd K.C. Kent , Mason Jeremy , Medico Enzo , Neuhauser Steven B. , Olson James M. , Peeper Daniel S. , Rueda Oscar M. , Seong Je Kyung , Trusolino Livio , Vinolo Emilie , Wechsler-Reya Robert J. , Weinstock David M. , Welm Alana , Weroha S. John , Amant Frédéric , Pfister Stefan M. , Kool Marcel , Parkinson Helen , Butte Atul J. , Bult Carol J.
Published: July 2024

A figure showing the process of generating and using PDX models.
Data from “Personalized Cancer Therapy”: A Publicly Available Precision Oncology Resource
Authors: Kurnit Katherine C. , Bailey Ann M. , Zeng Jia , Johnson Amber M. , Shufean Md. Abu , Brusco Lauren , Litzenburger Beate C. , Sánchez Nora S. , Khotskaya Yekaterina B. , Holla Vijaykumar , Simpson Amy , Mills Gordon B. , Mendelsohn John , Bernstam Elmer , Shaw Kenna , Meric-Bernstam Funda
Published: July 2024

Abstract
High-throughput genomic and molecular profiling of tumors is emerging as an important clinical approach. Molecular profiling is increasingly being used to guide cancer patient care, especially in advanced and incurable cancers. However, navigating the scientific literature to make evidence-based clinical decisions based on molecular profiling results is overwhelming for many oncology clinicians and researchers. The Personalized Cancer Therapy website (www.personalizedcancertherapy.org) was created to provide an online resource for clinicians and researchers to facilitate navigation of available data. Specifically, this resource can be used to help identify potential therapy options for patients harboring oncogenic genomic alterations. Herein, we describe how content on www.personalizedcancertherapy.org is generated and maintained. We end with case scenarios to illustrate the clinical utility of the website. The goal of this publicly available resource is to provide easily accessible information to a broad oncology audience, as this may help ease the information retrieval burden facing participants in the precision oncology field. Cancer Res; 77(21); e123–6. ©2017 AACR.
FOXP4 Is a Direct YAP1 Target That Promotes Gastric Cancer Stemness and Drives Metastasis
Authors: Liu Xiaoli , Chen Bonan , Xie Fuda , Wong Kit Yee , Cheung Alvin H.K. , Zhang Jinglin , Wu Qian , Fang Canbin , Hu Jintao , Wang Shouyu , Xu Dazhi , Chen Jianwu , Wang Yuzhi , Wong Chi Chun , Chen Huarong , Wu William K.K. , Yu Jun , Chan Michael W.Y. , Tsang Chi Man , Lo Kwok Wai , Tse Gary M.K. , To Ka-Fai , Kang Wei
Published: July 2024

The Hippo–YAP1 pathway is an evolutionally conserved signaling cascade that controls organ size and tissue regeneration. Dysregulation of Hippo–YAP1 signaling promotes initiation and progression of several types of cancer, including gastric cancer. As the Hippo–YAP1 pathway regulates expression of thousands of genes, it is important to establish which target genes contribute to the oncogenic program driven by YAP1 to identify strategies to circumvent it. In this study, we identified a vital role of forkhead box protein 4 (FOXP4) in YAP1-driven gastric carcinogenesis by maintaining stemness and promoting peritoneal metastasis. Loss of FOXP4 impaired gastric cancer spheroid formation and reduced stemness marker expression, whereas FOXP4 upregulation potentiated cancer cell stemness. RNA sequencing analysis revealed SOX12 as a downstream target of FOXP4, and functional studies established that SOX12 supports stemness in YAP1-induced carcinogenesis. A small-molecule screen identified 42-(2-tetrazolyl) rapamycin as a FOXP4 inhibitor, and targeting FOXP4 suppressed gastric cancer tumor growth and enhanced the efficacy of 5-fluorouracil chemotherapy in vivo. Collectively, these findings revealed that FOXP4 upregulation by YAP1 in gastric cancer regulates stemness and tumorigenesis by upregulating SOX12. Targeting the YAP1–FOXP4–SOX12 axis represents a potential therapeutic strategy for gastric cancer.

Significance: Hippo–YAP1 signaling maintains stemness in gastric cancer by upregulating FOXP4, identifying FOXP4 as a stemness biomarker and therapeutic target that could help improve patient outcomes.
AFDN Deficiency Promotes Liver Tropism of Metastatic Colorectal Cancer
Authors: Liao Shaoxia , Deng Jingwen , Deng Mengli , Chen Chaoyi , Han Fengyan , Ye Kehong , Wu Chenxia , Pan Lvyuan , Lai Maode , Tang Zhe , Zhang Honghe
Published: July 2024

Liver metastasis is a major cause of morbidity and mortality in patients with colorectal cancer. A better understanding of the biological mechanisms underlying liver tropism and metastasis in colorectal cancer could help to identify improved prevention and treatment strategies. In this study, we performed genome-wide CRISPR loss-of-function screening in a mouse colorectal cancer model and identified deficiency of AFDN, a protein involved in establishing and maintaining cell–cell contacts, as a driver of liver metastasis. Elevated AFDN expression was correlated with prolonged survival in patients with colorectal cancer. AFDN-deficient colorectal cancer cells preferentially metastasized to the liver but not in the lungs. AFDN loss in colorectal cancer cells at the primary site promoted cancer cell migration and invasion by disrupting tight intercellular junctions. Additionally, CXCR4 expression was increased in AFDN-deficient colorectal cancer cells via the JAK-STAT signaling pathway, which reduced the motility of AFDN-deficient colorectal cancer cells and facilitated their colonization of the liver. Collectively, these data shed light on the mechanism by which AFDN deficiency promotes liver tropism in metastatic colorectal cancer.

Significance: A CRISPR screen reveals AFDN loss as a mediator of liver tropism in colorectal cancer metastasis by decreasing tight junctions in the primary tumor and increasing interactions between cancer cells and hepatocytes.
SJPedPanel: A Pan-Cancer Gene Panel for Childhood Malignancies to Enhance Cancer Monitoring and Early Detection
Authors: Kolekar Pandurang , Balagopal Vidya , Dong Li , Liu Yanling , Foy Scott , Tran Quang , Mulder Heather , Huskey Anna L.W. , Plyler Emily , Liang Zhikai , Ma Jingqun , Nakitandwe Joy , Gu Jiali , Namwanje Maria , Maciaszek Jamie , Payne-Turner Debbie , Mallampati Saradhi , Wang Lu , Easton John , Klco Jeffery M. , Ma Xiaotu
Published: July 2024

Purpose:

The purpose of the study was to design a pan-cancer gene panel for childhood malignancies and validate it using clinically characterized patient samples.

Experimental Design:

In addition to 5,275 coding exons, SJPedPanel also covers 297 introns for fusions/structural variations and 7,590 polymorphic sites for copy-number alterations. Capture uniformity and limit of detection are determined by targeted sequencing of cell lines using dilution experiment. We validate its coverage by in silico analysis of an established real-time clinical genomics (RTCG) cohort of 253 patients. We further validate its performance by targeted resequencing of 113 patient samples from the RTCG cohort. We demonstrate its power in analyzing low tumor burden specimens using morphologic remission and monitoring samples.

Results:

Among the 485 pathogenic variants reported in RTCG cohort, SJPedPanel covered 86% of variants, including 82% of 90 rearrangements responsible for fusion oncoproteins. In our targeted resequencing cohort, 91% of 389 pathogenic variants are detected. The gene panel enabled us to detect ∼95% of variants at allele fraction (AF) 0.5%, whereas the detection rate is ∼80% at AF 0.2%. The panel detected low-frequency driver alterations from morphologic leukemia remission samples and relapse-enriched alterations from monitoring samples, demonstrating its power for cancer monitoring and early detection.

Conclusions:

SJPedPanel enables the cost-effective detection of clinically relevant genetic alterations including rearrangements responsible for subtype-defining fusions by targeted sequencing of ∼0.15% of human genome for childhood malignancies. It will enhance the analysis of specimens with low tumor burdens for cancer monitoring and early detection.
Supplementary Table 2 from Generation, Transcriptomic States, and Clinical Relevance of CX3CR1+ CD8 T Cells in Melanoma
Authors: Ishigaki Hirohito , Yamauchi Takayoshi , Long Mark D. , Hoki Toshifumi , Yamamoto Yuta , Oba Takaaki , Ito Fumito
Published: July 2024

Supplementary Table 2
Supplementary Figure 2 from Generation, Transcriptomic States, and Clinical Relevance of CX3CR1+ CD8 T Cells in Melanoma
Authors: Ishigaki Hirohito , Yamauchi Takayoshi , Long Mark D. , Hoki Toshifumi , Yamamoto Yuta , Oba Takaaki , Ito Fumito
Published: July 2024

Gating strategy to analyze CX3CR1 expression on CD8+ T cells in human melanoma TILs.
Supplementary Figure 1 from Generation, Transcriptomic States, and Clinical Relevance of CX3CR1+ CD8 T Cells in Melanoma
Authors: Ishigaki Hirohito , Yamauchi Takayoshi , Long Mark D. , Hoki Toshifumi , Yamamoto Yuta , Oba Takaaki , Ito Fumito
Published: July 2024

The scheme of the generation of Pmel-1 Cd2-cre/Cx3cr1DTR/DTR mice.
Figure 4 from Generation, Transcriptomic States, and Clinical Relevance of CX3CR1+ CD8 T Cells in Melanoma
Authors: Ishigaki Hirohito , Yamauchi Takayoshi , Long Mark D. , Hoki Toshifumi , Yamamoto Yuta , Oba Takaaki , Ito Fumito
Published: July 2024

Antigen-specific CD8+ T cells CX3CR1− CD8+ T cells differentiate to CX3CR1+ subsets within the tumor. A, Experimental protocol. B16F10-bearing mice were either injected with ex vivo-activated Pmel-1 CD8+ T cells (WT) or Pmel-1 Cd2-cre/Cx3cr1DTR/DTR CD8+ T cells. The scheme of generation of Pmel-1 Cd2-cre/Cx3cr1DTR/DTR mice is shown in Supplementary Fig. S1. B, Representative contour plots showing CD27/DTR expression of CD8 and CD90.1-gated Cd2-cre/Cx3cr1DTR/DTR CD8+ T cells in the spleen with or without vaccination with hgp100 and CD40/TLR7 agonists in vivo. C, Representative contour plots of CD8 and CD90.1-gated cells in the spleen (top) and the tumor (bottom). Numbers, percentage of the CX3CR1+ subset. Data panels right show frequency of CX3CR1+ CD8+ T cells [wild type (WT)] or DTR-expressing Pmel-1 Cd2-cre/Cx3cr1DTR/DTR CD8+ T cells (DTR/DTR) obtained from four mice in each group. NS, not significant by two-tailed unpaired t test.
Figure 3 from Generation, Transcriptomic States, and Clinical Relevance of CX3CR1+ CD8 T Cells in Melanoma
Authors: Ishigaki Hirohito , Yamauchi Takayoshi , Long Mark D. , Hoki Toshifumi , Yamamoto Yuta , Oba Takaaki , Ito Fumito
Published: July 2024

The differentiation of CX3CR1− to CX3CR1+ CD8+ T cells could occur in the periphery without migration to secondary lymphoid organs. A, Experimental protocol. B, Frequency of endogenous CD90.1− CD8+ T cells and infused Pmel-1 CD90.1+ CD8+ T cells in the spleen was analyzed after treatment with FTY720 or control vehicle. Data right show the frequency of endogenous CD90.1− CD8+ T cells and infused Pmel-1 CD90.1+ CD8+ T cells. C, Representative contour plots showing CD27/CX3CR1 expression of CD8 and CD90.1-gated cells in the spleen (top) and the tumor (bottom). Numbers, percentage of the CX3CR1+ subset. Data right show the frequency of CX3CR1+ CD8+ T cells obtained from seven mice in each group. P values by two-tailed unpaired t test. NS, not significant. Mean (±SEM).
Data from Generation, Transcriptomic States, and Clinical Relevance of CX3CR1+ CD8 T Cells in Melanoma
Authors: Ishigaki Hirohito , Yamauchi Takayoshi , Long Mark D. , Hoki Toshifumi , Yamamoto Yuta , Oba Takaaki , Ito Fumito
Published: July 2024

Abstract
Recent progress in single-cell profiling technologies has revealed significant phenotypic and transcriptional heterogeneity in tumor-infiltrating CD8+ T cells. However, the transition between the different states of intratumoral antigen-specific CD8+ T cells remains elusive. Here, we sought to examine the generation, transcriptomic states, and the clinical relevance of melanoma-infiltrating CD8+ T cells expressing a chemokine receptor and T-cell differentiation marker, CX3C chemokine receptor 1 (CX3CR1). Analysis of single-cell datasets revealed distinct human melanoma-infiltrating CD8+ T-cell clusters expressing genes associated with effector T-cell function but with distinguishing expression of CX3CR1 or PDCD1. No obvious impact of CX3CR1 expression in melanoma on the response to immune checkpoint inhibitor therapy was observed while increased pretreatment and on-treatment frequency of a CD8+ T-cell cluster expressing high levels of exhaustion markers was associated with poor response to the treatment. Adoptively transferred antigen-specific CX3CR1− CD8+ T cells differentiated into the CX3CR1+ subset in mice treated with FTY720, which inhibits lymphocyte egress from secondary lymphoid tissues, suggesting the intratumoral generation of CX3CR1+ CD8+ T cells rather than their trafficking from secondary lymphoid organs. Furthermore, analysis of adoptively transferred antigen-specific CD8+ T cells, in which the Cx3cr1 gene was replaced with a marker gene confirmed that CX3CR1+ CD8+ T cells could directly differentiate from the intratumoral CX3CR1− subset. These findings highlight that tumor antigen–specific CX3CR1− CD8+ T cells can fully differentiate outside the secondary lymphoid organs and generate CX3CR1+ CD8+ T cells in the tumor microenvironment, which are distinct from CD8+ T cells that express markers of exhaustion.
Significance:
Intratumoral T cells are composed of heterogeneous subpopulations with various phenotypic and transcriptional states. This study illustrates the intratumoral generation of antigen-specific CX3CR1+ CD8+ T cells that exhibit distinct transcriptomic signatures and clinical relevance from CD8+ T cells expressing markers of exhaustion.
Implementation of a Microbiological Surveillance Protocol in a Portuguese Tertiary Care Academic Endoscopy Unit
Authors: Monteiro Cristiana , Lima Jorge , Ribeiro Tiago , Gonçalves Maria Helena , Gonçalves Natália , Oliveira Carina , Soares Liliana , Carvalho Ana , Vilas-Boas Filipe , Ribeiro Maria Manuela , Macedo Guilherme , Barros Sónia
Published: July 2024

Introduction: International societies recommend microbiological surveillance of endoscopes to reduce the incidence of endoscope-associated infections, particularly for duodenoscopes. However, surveillance protocols are not internationally standardized, both regarding sample collection, processing, and culture. This study aims to provide a framework protocol encompassing the experience of a tertiary large volume endoscopy center and the microbiology laboratory for collecting and culturing of endoscope samples for microbiological surveillance. Methods: A sample collection and processing protocol was designed as a result of a cooperation between the Endoscopy Center of the Gastroenterology Department and the Microbiology Laboratory of the Department of Clinical Pathology. This protocol reflects international recommendations in this topic and the human and technological resources of the involved departments. Results: The established protocol for collecting samples varies according to the type and model of endoscope. The specimens are collected as sterile saline liquid samples, as well as swabs (with and without transport media). Together with the collection of samples from the endoscope, samples from the final rinse water as well as the water bottle are also collected. For duodenoscopes and curvilinear echoendoscopes, we perform microbiological surveillance every 3 months; for gastroscopes and colonoscopes, at least, once a year; and for specific endoscopes, such as the pediatric or dual-channel therapeutic endoscopes, enteroscopes, or radial echoendoscopes, every 6 months. Conclusion: Endoscopy units should have detailed protocols for microbiological surveillance of endoscopes. These protocols should be drawn up by a multidisciplinary team that includes endoscopy nurses, gastroenterologists, microbiologists, and the antimicrobial stewardship team, following international recommendations, adapted to each institution resources.
Targeting CK1δ and CK1ε as a New Therapeutic Approach for Clear Cell Renal Cell Carcinoma
Authors: Lin Yu-Chen , Sun Ding-Ping , Hsieh Tsung-Han , Chen Chun-Han
Published: July 2024

Introduction: Kidney cancer ranks as the ninth most common cancer in men and the fourteenth in women globally, with renal cell carcinoma (RCC) being the most prevalent type. Despite advances in therapeutic strategies targeting angiogenesis and immune checkpoints, the absence of reliable markers for patient selection and limited duration of disease control underline the need for innovative approaches. CK1δ and CK1ε are highly conserved serine/threonine kinases involved in cell cycle regulation, apoptosis, and circadian rhythm. While CK1δ dysregulation is reportedly associated with breast and bladder cancer progression, their role in RCC remains elusive. This study aimed to investigate the feasibility of CK1δ/ε as new therapeutic targets for RCC patients. Methods: The relationship between CK1δ/ε and RCC progression was evaluated by the analysis of microarray dataset and TCGA database. The anticancer activity of CK1δ/ε inhibitor was examined by MTT/SRB assay, and apoptotic cell death was analyzed by flow cytometry and Western blotting. Results: Our data demonstrate that the gene expression of CSNK1D and CSNK1E is significantly higher in clear cell RCC (ccRCC) tissues compared to normal kidney samples, which is correlated with lower survival rates in ccRCC patients. SR3029, a selective inhibitor targeting CK1δ/ε, significantly suppresses the viability and proliferation of ccRCC cell lines regardless of the status of VHL deficiency. Importantly, the inhibitor promotes the population of subG1 cells and induces apoptosis, and ectopically expression of CK1δ partially rescued SR3029-induced apoptosis in ccRCC cells. Conclusion: These findings underscore the crucial role of CK1δ and CK1ε in ccRCC progression, suggesting CK1δ/ε inhibitors as new therapeutic options for ccRCC patients.
Sleep duration and cognitive function, The Akershus Cardiac Examination 1950 Study
Authors: Ihle-Hansen Hege , Einvik Gunnar , Hagberg Guri , Thommessen Bente , Rønning Ole Morten , Vigen Thea , Lyngbakken Magnus Nakrem , Berge Trygve , Røsjø Helge , Tveit Arnljot , Ihle-Hansen Håkon
Published: July 2024

INTRODUCTION: Sleep duration are proposed as a lifestyle-related risk factor for cognitive impairment. We investigated the association between sleep duration and cognitive function in a large population-based cohort aged 62-65 years.
METHODS: Cross-sectional analyses from the The Akershus Cardiac Examination 1950 Study. Linear and non-linear models were conducted to explore the association between self-reported sleep duration and cognitive function, adjusted for established risk factors for cognitive impairment.
RESULTS: We included 3,348 participants, mean age (SD) was 63.9 ±0.6 years, 48.2% were women and 47.9% had education >12 years. Mean sleep duration (SD) was 7.0±1.0 hours, and 10.2% had abnormal sleep duration (<6 or >8 hours). Individuals reporting <6 hours or >8 hours of sleep scored significantly lower on MoCA test and Delayed recall trial in adjusted analysis.
CONCLUSIONS: Sleep duration showed an inverted U-shaped association with global cognitive function and memory, suggesting that both shortened and prolonged sleep are related to adverse brain health.
Retinal sensitivity in macular subfields and their association with contrast sensitivity in early and intermediate age-related macular degeneration
Authors: Chan Eric J. , Anders Philipp , Garobbio Simona A. , Hall Ursula , Gabrani Chrysoula , Pfau Kristina , Camenzind Zuche Hanna , Futterknecht Stefan , Pfau Maximilian , Herzog Michael , Traber Ghislaine L. , Scholl Hendrik P.N.
Published: July 2024

Purpose
To evaluate retinal sensitivity in subfields and its association with the novel quick contrast sensitivity function (qCSF) in patients with early age-related macular degeneration (eAMD), in patients with intermediate AMD (iAMD), and in healthy controls.

Methods
In this prospective longitudinal study retinal sensitivity of a customized 24-point grid was assessed by microperimetry Macular Integrity Assessment (MAIA, CenterVue, Padova, Italy) and divided into different subfields. The Multiple Contrast Vision Meter (Adaptive Sensory Technology, San Diego, CA) was used for qCSF testing. Linear models were used to test the association of functional metrics with variables of interest.

Results
92 study eyes from 92 participants were analyzed (13 eAMD, 31 iAMD, and 48 controls). Microperimetry subfield comparison showed significant differences (p<0.0001) in the control group between superior and inferior hemifield as well as between central and peripheral subfields. For eAMD significant differences were found between central and peripheral subfields (p<0.001) and specific subfields (p<0.05) and finally for iAMD between specific quadrants (p<0.05) and specific squares (p<0.05). Significant associations of retinal sensitivity with qCSF metrics were found for the area underneath the logarithmic contrast sensitivity function (AULCSF), contrast acuity (CA) and for the contrast sensitivity at specific spatial frequencies.

Conclusions
This study showed significant differences in the evaluated retinal sensitivity subfields providing localized natural history data for retinal sensitivity in healthy controls, and patients with eAMD and iAMD.
Metamorphopsia with SMART syndrome: A case report.
Authors: Flain Luke , Lay Aisha , Gadil Eden , James Karlie , Thanancheyan Sanchayan , Bacchi Stephen , Goh Rudy
Published: July 2024

Introduction: SMART syndrome is a rare complication of brain radiotherapy. This is the first described presentation of SMART syndrome with metamorphopsia which responded to Aspirin, Verapamil and high dose L-Arginine therapy.

Case presentation: A 43 year old man presented with three weeks of migraine headaches with metamorphopsia and complex visual hallucinations affecting the left lower quadrant of both visual fields. This occurred on a background of high dose radiotherapy for right cerebellar astrocytoma 32 years ago. MRI brain demonstrated unilateral gyriform enhancement and FLAIR hyperintense cortical swelling in the right occipital lobe consistent with SMART syndrome.

Conclusion: Unusual presentations of SMART syndrome exist and require consideration in all patients with focal neurological deficit post-brain radiotherapy. Validated diagnostic and treatment modalities for SMART syndrome are urgently required.
Changes in Mutations of Cell-Free DNA and Liver Tumor Tissue in Patients with Advanced Hepatocellular Carcinoma before and after Introduction of Lenvatinib
Authors: Tsuruoka Mio , Ninomiya Masashi , Inoue Jun , Iwata Tomoaki , Sano Akitoshi , Sato Kosuke , Onuki Masazumi , Sawahashi Satoko , Masamune Atsushi
Published: July 2024

Introduction: Cell-free DNA (cfDNA) is expected to contribute to the decision for treatment and prediction of effects with minimally invasion. We investigated the correlation between gene mutations before and after lenvatinib (LEN) treatment and its effectiveness, in order to find advanced hepatocellular carcinoma (HCC) patients who would benefit greatly from the therapy. Methods: We analyzed cfDNA before and 6–8 weeks after the start of treatment in 20 advanced HCC patients who started LEN. A next-generation sequencer was used for CTNNB1 and TP53. Concerning TERT promoter, −124C>T and −146C>T mutations are researched using digital PCR. In addition, we examined liver tumor biopsy tissues by the same method. Computerized tomography evaluation was performed at 6–8 weeks and 3–4 months to assess the efficacy. Results: Frequencies of TERT promoter, CTNNB1, and TP53 mutations in pretreatment cfDNA were 45%, 65%, and 65%, but 53%, 41%, and 47% in HCC tissues, respectively. There were no clear correlations between these gene mutations and the disease-suppressing effect or progression-free survival. Overall, there were many cases showing a decrease in mutations after LEN treatment. Integrating the reduction of CTNNB1 and TP53 genetic mutations increased the potential for disease suppression. Conclusion: This study suggests that analysis of cfDNA in advanced HCC patients may be useful for identifying LEN responders and determining therapeutic efficacy. Furthermore, it has potential for selecting responders for other molecular-targeted drugs.