bluuebunny/crossref_metadata_2025 huggingface dataset:
An extension of Rees’ theorem and two interpretations of a vector in the joint reduction lattice
Authors: D’Cruz Clare , Masuti Shreedevi K.
Published: July 2024

In [D. Rees, Hilbert functions and pseudo-rational local rings of dimension two, J. London Math. Soc. (2) 24 (1981) 467–479], Rees gave a characterization for the normal joint reduction number zero of two [Formula: see text]-primary ideals in an analytically unramified Cohen–Macaulay local ring of dimension two. Rees’ result is a generalization of Zariski’s product theorem for complete ideals in a regular local ring of dimension two. The aim of this paper is to extend Rees’ theorem for the ordinary powers of [Formula: see text]-primary ideals [Formula: see text] and [Formula: see text] in a Cohen–Macaulay local ring of dimension two. Following Rees’ approach, we define the modified Koszul homology modules [Formula: see text] for a joint reduction [Formula: see text] of [Formula: see text] and [Formula: see text]. Under the additional assumption that the associated graded rings of [Formula: see text] and [Formula: see text] have positive depth, we obtain a characterization of the joint reduction number zero of [Formula: see text] and [Formula: see text] in terms of the vanishing of the module [Formula: see text], as well as in terms of the Hilbert coefficients and the bigraded Hilbert coefficients. More generally, we introduce the joint reduction lattice and study the vanishing of [Formula: see text] for any [Formula: see text]. This gives a characterization for a vector [Formula: see text] to be in the joint reduction lattice of [Formula: see text] and [Formula: see text]. We also give a cohomological interpretation of these theorems by investigating the local cohomology modules of the bigraded extended Rees algebra. This gives another characterization for a vector [Formula: see text] to be in the joint reduction lattice and also extends a recent result of Masuti and Verma in [Local cohomology of bigraded Rees algebras and normal Hilbert coefficients, J. Pure Appl. Algebra 218(5) (2014) 904–918] for ordinary powers of ideals.
Time Sequence Simulation of Cross-Fault Mountain Tunnel Under Dislocation and Seismic Input
Authors: Li Liqun , Chen Zhiyi
Published: July 2024

Mountain tunnels built near faults often suffer from significant permanent deformation and structural dislocation during seismic activity. In this paper, we present a rock-fault-tunnel geological model with a transition area between the hanging wall and the foot wall which allows the free slippery growth inside the area. A time-sequenced load based on design code and fault activity is conducted in this model to simulate dynamic seismic input after fault dislocation. In our case, a reverse fault with a tunnel cross has been created with this method. A 30[Formula: see text]cm fault dislocation is simulated by putting the displacement boundary of the hanging wall with a compression vector and the seismic wave is input from the bottom boundary as acceleration waveform adjusted to 0.4[Formula: see text]g. The model simulates the uplift of the hanging wall and the growth of the slip surface, and reveals the extension mechanism of the triangular shear zone of shear rupture of the surrounding rock due to the extrusion of the reverse fault during the propagation of the reverse fault. The seismic wave with a three-way acceleration was input after the dislocation process. The simulation indicates that with the gradual uplift of the hanging wall, the rock body of the fracture zone shows a more significant large deformation flow trend and a more significant horizontal slip flow. Under reverse fault thrust, the width of the shear effect influence zone is around 300[Formula: see text]m. A decreasing trend of accumulated strain can be found at the interface due to acceleration input. Dislocation-seismic time-sequence loading may underestimate its damage effects.
Drug delivery strategies for porphyrin-based photosensitizers in photodynamic antimicrobial chemotherapy
Authors: Murage Margaret W. , Amuhaya Edith K. , Mbatia Betty N. , Muge Edward K. , Derese Solomon
Published: July 2024

In the face of increasing antimicrobial resistance (AMR) and the looming threat of a return to a pre-antibiotics era, the exploration of alternative antimicrobial strategies becomes imperative. Among these, Photodynamic Antimicrobial Chemotherapy (PACT) stands out as a promising solution due to its multi-target principle, diverging from the key-lock mechanism inherent in conventional antibiotics. However, the hydrophobic nature, non-targeted distribution, stability issues, and limited tissue penetration of photosensitizers (PSs), particularly the extensively studied porphyrin-based compounds, pose structural limitations impacting their bioavailability and effective delivery to target sites. Therefore, various delivery strategies are adopted to improve their effectiveness in PACT. This includes attaching the PS to a variety of delivery vehicles such as nanoparticles, and liposomes, or encapsulating them in nanostructures, such as micelles or dendrimers. This helps protect the PS from degradation, improve their solubility and bioavailability, and enhance their photophysical and photochemical properties, ultimately improving their effectiveness in PACT. In this paper, recent studies focusing on strategies used to improve the delivery of porphyrin-based PS in PACT are reviewed.
Design and synthesis of fluorescent BODIPY derivatives with D-A structure for cancer cell imaging
Authors: Xiao Yutong , Tong Simiao , Yang Mengqian , Lin Xiao , Xu Man , Wu Fengshou
Published: July 2024

Boron-dipyrromethene (BODIPY) as a traditional fluorescent dye has received increasing attention because of its high molar extinction coefficient, easy modification, and good light stability. In this work, three BODIPY compounds (BDP-1, BDP-2 and BDP-3) were designed and synthesized by introducing PEG chains and a naphthalimide (NI) group onto the parent structure of BODIPY. Due to the electron-withdrawing properties of NI, the compounds of BDP-2 and BDP-3 formed a typical donor (D)-acceptor (A) structure, which led to the red-shifted absorption and fluorescence spectrum. The synthesized BODIPY exhibited intense green emission, with fluorescence quantum yield of 0.66, 0.29, and 0.19 for BDP-1, BDP-2 and BDP-3 respectively. The decrease in fluorescence of BDP-2 and BDP-3 was probably ascribed to the enhanced intramolecular charge transfer because of the introduction of the NI group. The good biocompatibility and low cytotoxicity of the synthesized BODIPY compounds were verified by the CCK-8 assay. The subcellular localization of the three compounds was further evaluated through a confocal laser scanning microscope. The results showed that these BODIPY derivatives were mainly localized in the lysosomes of cancer cells. Thus, the synthesized BODIPY fluorescent dyes show promising applications in tumor imaging benefiting from their good biocompatibility and strong fluorescence.
Export Diversification, Quality and Global Value Chain: A Cross-country Analysis
Authors: Guha-Khasnobis Basudeb , Aditya Anwesha
Published: July 2024

This paper critically examines the impact of countries’ participation and positions in Global Value Chains (GVCs) on their export diversification and quality for 43 G20 and OECD countries over the period 1990–2015. GMM dynamic panel estimation reveals that deeper GVC integration significantly influences export structures, with countries positioned downstream in the value chain exhibiting more diversified exports (overall and at the intensive margin) but have concentrated exports at the extensive margin and geographically. Conversely, upstream, more factor-based GVC activities tend to result in less diversified export portfolios. Greater GVC participation leads to a more diversified export product basket but more concentrated export destinations in terms of the Hirschman index. However, the association between export diversification and GVC participation varies across measures of diversification and country’s level of economic development. We further find that countries and sectors having larger export share in downstream of the supply chain and have a lower extent of GVC participation, export quality differentiated product. These outcomes suggest that GVC participation and position play crucial roles in shaping national export strategies and economic resilience, with downstream activities offering pathways to enhanced export diversification and quality improvement. The study contributes to the understanding of how global production fragmentation impacts the complexity and sophistication of countries’ export baskets. The outcomes provide guidance for policymakers to strategically leverage GVC engagement to foster export diversification, quality improvement and economic resilience.
Structuring Success
Authors: Neville-Neil George V.
Published: July 2024

The problem with software structure is people do not really learn it until they really need it.
An Umbrella Review of Reporting Quality in CHI Systematic Reviews: Guiding Questions and Best Practices for HCI
Authors: Rogers Katja , Hirzle Teresa , Karaosmanoglu Sukran , Palomino Paula Toledo , Durmanova Ekaterina , Isotani Seiji , Nacke Lennart E.
Published: July 2024

Systematic reviews (SRs) are vital to gathering and structuring knowledge, yet descriptions of their procedures are often inadequate. In human–computer interaction (HCI), SRs are still uncommon but gaining momentum, which prompted us to explore how SRs are reported at CHI—the flagship HCI conference venue. To assess the reporting quality of CHI reviews that aim for a systematic approach, we conducted an umbrella review and applied reporting guidelines for SRs (PRISMA and ENTREQ) to our corpus. We contribute the first exploration of how well SRs at CHI meet guidelines for reporting quality, showcasing strategies for improvement in reporting and conducting SRs especially in the domains of appraisal, synthesis, and documentation (i.e., protocol development). Finally, we present guiding questions for HCI researchers and practitioners for reporting SRs, as well as suggestions for best practices.
Fine-Grained Hardware Profiling - Are You Using the Right Tools?
Authors: Kakaraparthy Aarati , Patel Jignesh M.
Published: July 2024

We consider the problem of fine-grained hardware profiling, i.e., profiling the hardware while the desired section of the program is executing. Although this requirement is frequently encountered in practice, its importance has not been emphasized in literature so far. In this work, we compare and validate three tools for performing fine-grained profiling on Linux platforms - perf, PAPI, and a homegrown tool PMU-metrics. perf has been used in the past for fine-grained profiling in an erroneous manner, producing inaccurate metrics as a result. On the other hand, PAPI and PMU-metrics produce accurate metrics for profiling at thems-scale, while PMUmetrics enables profiling even at the µs-scale. Thus, we hope that our analysis will help systems practitioners choose the right tool for performing fine-grained profiling at different time scales.
Reminiscences on Influential Papers
Authors: Tözün Pınar
Published: July 2024

This issue's contributors all work at the intersection of machine learning and databases. Coincidentally, three of them picked papers that received the VLDB 10-Year Best Paper award, and one of them picked a paper that, in my opinion, should receive the CIDR Test-of-Time award at some point. Their write-ups highlight very well why these four papers still continue to leave a mark on us personally and the real-world data systems. Enjoy reading!

While I will keep inviting members of the data management community, and neighboring communities, to contribute to this column, I also welcome unsolicited contributions. Please contact me if you are interested.
Visualizing, Exploring and Analyzing Big Data: A 6-Year Story
Authors: Bikakis Nikos , Papastefanatos George , Chrysanthis Panos K. , Papemmanuil Olga , Auber David , Frey Steffen , Fujishiro Issei , Hauptmann Hanna , Liu Shixia , Ma Kwan-Liu , Schreck Tobias , Sedlmair Michael , Sharaf Mohamed A.
Published: July 2024

Information Visualization has been one of the cornerstones of Data Science, turning the abundance of Big Data being produced through modern systems into actionable knowledge. Indeed, the Big Data era has realized the availability of voluminous datasets that are dynamic, multidimensional, noisy and heterogeneous in nature. Transforming a data-curious user into someone who can access and analyze that data is even more burdensome now for a great number of users with little or no support and expertise on the data processing part.
Democratizing Direct-to-Cell Low Earth Orbit Satellite Networks
Authors: Liu Lixin , Li Yuanjie , Li Hewu , Yang Jiabo , Liu Wei , Lan Jingyi , Wang Yufeng , Li Jiarui , Wu Jianping , Wu Qian , Liu Jun , Lai Zeqi
Published: July 2024

The emergent Direct-to-cell Low Earth Orbit (LEO) satellites promise to eliminate cellular coverage dead zones by enabling direct network access to our regular phones and IoTs everywhere on Earth via 4G, 5G, and beyond. However, their large-scale deployment can be impeded by scarce orbital slots in space, a lack of licensed cellular spectrums, and prohibitive capital costs for satellite deployment and operation. This article explores how to enable multi-tenant direct-to-cell LEO satellites as a cost-effective win-win solution for satellite operators, mobile operators, and users. We demonstrate that the state-of-the-art cellular networks' stateful hop-by-hop session-based architecture restricts the LEO satellite multi-tenancy. To remove this technical barrier, we propose MOSAIC [1], an alternative scheme to shift from the hop-by-hop session-based cellular service to pay-as-you-go satellite self-service. MOSAIC lets mobile operators supply their users with one-time digitally signed tokens as "coins" to pay for local satellite access on demand. Any satellite operator's authentic satellite can accept these tokens to serve this user without pre-establishing sessions or contacting mobile operators. Akin to cloud computing, this paradigm lets satellite operators flexibly lease their satellites to more mobile operators or higher revenues and return on investment, and allows mobile operators and users to enjoy competitive satellites for complementary coverage and cost optimizations. Our evaluations with the real satellite data and commodity 3GPP NTN protocol stack validate MOSAIC's scalability and performance advantages compared to the state-of-the-art.
Predicting Surgical Outcomes Using Wearables
Authors: Zhang Jingwen , Li Dingwen , Dai Ruixuan , Cos Heidy , Williams Gregory A. , Raper Lacey , Hammill Chet W. , Lu Chenyang
Published: July 2024

Accurate prediction of readmission and severe complication risks during the pre-operative stage is crucial for clinical decision-making. In addition to traditional static clinical data, the activity and physiological data collected by commercial wearable devices such as Fitbit wristbands provide valuable complementary information. However, data from wearables are often incomplete and noisy, presenting challenges in extracting clinically meaningful features from fine-grained time series data. In this paper, we propose a pipeline to develop predictive models using pre-operative wearable data to predict surgical outcomes in patients undergoing pancreatic surgeries. The core of this pipeline is a multi-level feature engineering framework designed to extract high-level features from wearable data, which are then combined with static clinical characteristics to form the input for the predictive model. In a clinical study involving 61 patients, our approach improved the Area Under the Receiver Operating Characteristic (AUROC) by 44% compared to the existing risk calculator employed in clinical practice.
Clogging of Noncohesive Suspension Flows
Authors: Marin Alvaro , Souzy Mathieu
Published: July 2024

When flowing through narrow channels or constrictions, many-body systems exhibit various flowing patterns, yet they can also get stuck. In many of these systems, the flowing elements remain as individuals (they do not aggregate or merge), sharing strong analogies among each other. This is the case for systems as contrasting as grains in a silo and pedestrians passing through tight spaces. Interestingly, when these entities flow within a fluid medium, numerous similarities persist. However, the fluid dynamics aspects of such clogging events, such as interstitial flow, liquid pressure, and hydrodynamic interactions, has only recently begun to be explored. In this review, we describe parallels with dry granular clogging and extensively analyze phenomena emerging when particles coexist with fluid in the system. We discuss the influence of diverse flow drive, particle propulsion mechanisms, and particle characteristics, and we conclude with examples from nature.
Cell-cell crosstalk between fat cells and immune cells
Authors: Liu Jiadai , Chen Yong
Published: July 2024

Obesity is a metabolic disorder with pandemic-like implications, lacking viable pharmaceutical treatments currently. Thermogenic adipose tissues, including brown and beige adipose tissues, play an essential role in regulating systemic energy homeostasis and have emerged as appealing therapeutic targets for the treatment of obesity and obesity-related diseases. The function of adipocytes is subject to complex regulation by a cellular network of immune signaling pathways in response to environmental signals. However, the specific regulatory roles of immune cells in thermogenesis and relevant involving mechanisms are still not well understood. Here, we concentrate on our present knowledge of the interaction between thermogenic adipocytes and immune cells and present an overview of cellular and molecular mechanisms underlying immunometabolism in adipose tissues. We discuss cytokines, especially interleukins, which originate from widely variable sources, and their impacts on the development and function of thermogenic adipocytes. Moreover, we summarize the neuroimmune regulation in heat production and expand a new mode of intercellular communication mediated by mitochondrial transfer. The crosstalk between immune cells and adipocytes achieves adipose tissue homeostasis and systemic energy balance. A deep understanding of this intricate interaction would provide evidence for improving thermogenic efficiency by remodeling the immune microenvironment. Interventions based on these factors show a high potential to prevent adverse metabolic outcomes in patients with obesity.
The role of interleukin-10 in mitigating endoplasmic reticulum stress in aged mice through exercise
Authors: Marafon Bruno Brieda , Pinto Ana Paula , de Sousa Neto Ivo Vieira , da Luz Caroline Mantovani , Pauli José Rodrigo , Cintra Dennys Esper , Ropelle Eduardo Rochete , Simabuco Fernando Moreira , Pereira de Moura Leandro , de Freitas Ellen Cristini , Rivas Donato Americo , da Silva Adelino Sanchez Ramos
Published: July 2024

Aging elevates endoplasmic reticulum (ER) stress in skeletal muscle, potentially heightening inflammation by opposing interleukin-10 (IL-10) effects. This study found that short-term combined exercise boosted strength and IL-10 protein levels while reducing CHOP protein levels in older mice. In addition, IL-10-deficient mice exhibited increased ER stress markers, highlighting IL-10’s role in regulating ER stress in skeletal muscle. Consequently, combined exercise emerges as a therapeutic intervention to elevate IL-10 and adjust ER stress markers in aging.
Analysis of Vibration Characteristics of Hydraulic Excavator Device Under Flat Ground Conditions
Authors: Liu Kailei , Zhong Haifang , Chen Maoze , Yang Jing , Qiang Hongbin , Kang Shaopeng
Published: July 2024

Hydraulic excavators, characterized by their high efficiency and versatility, are crucial equipment in engineering construction. During the automatic excavation process, the excavator may experience resonance phenomena, which can affect the stability of the entire system. In order to study the vibration harmonic response of the excavator arm in the process of reciprocating motion, firstly, the model of the excavator arm is designed in three‐dimensional software, and the finite element meshing software is used to perform hexahedral meshing of the excavator arm model and define the material properties. Secondly, the modal analysis of the excavator arm is carried out by finite element simulation software, and the displacement and acceleration harmonic response analysis is carried out using the modal superposition method. Finally, the vibration experiment of reciprocating motion with different frequencies is carried out on the experimental platform of the excavator arm. The simulation and experimental results show that the maximum value of the displacement and acceleration response of the excavator arm corresponds to the frequency near the second‐order intrinsic frequency, and the excavator arm is greatly affected by the second‐order intrinsic frequency; controlling the frequency of the reciprocating motion of the hydraulic cylinder within 13 Hz can effectively avoid the resonance phenomenon of the excavator arm device.
Sociodemographic and Socioeconomic Factors Correlate with Late-Stage Pediatric Hodgkin Lymphoma and Rhabdomyosarcoma: A Report from the Children’s Oncology Group Registries
Authors: Ou Judy Y. , Kaddas Heydon K. , Alonzo Todd A. , Spector Logan G. , Fallahazad Negar , Owens Emily , Collin Lindsay J. , Green Adam L. , Kirchhoff Anne C.
Published: July 2024

Background:

We examined the association between late-stage diagnosis and individual- and community-level sociodemographic and socioeconomic characteristics among patients with pediatric Hodgkin lymphoma and rhabdomyosarcoma (RMS).

Methods:

We obtained Children’s Oncology Group data from 1999 to 2021 including summary stage [local (L), regional (R), and distant (D)], tumor subtype, demographics, and ZIP Code at diagnosis. We linked ZIP Codes to county-level redlining scores (C, D = greatest redlining), the Child Opportunity Index, and measures of segregation (racial dissimilarity indices). Logistic regressions calculated odds ratios for late-stage diagnosis and by race within tumor subtype.

Results:

In total, 5,956 patients with Hodgkin lymphoma and 2,800 patients with RMS were included. Late-stage diagnosis of Hodgkin lymphoma was correlated with Black race [ORDistant(D) vs. regional/local (R&L) = 1.38 (1.13–1.68)], being uninsured [ORD vs. R&L = 1.38 (1.09–1.75)], and subtype [nodular sclerosis vs. Other Hodgkin lymphoma: ORD vs. R&L = 1.64 (1.34–2.01), Untyped: ORD vs. R&L = 1.30 (1.04–1.63)]. Late-stage RMS was correlated with bilingual households [ORDistant/regional(D&R) vs. local(L) = 2.66 (1.03–6.91)] and tumor type [alveolar vs. embryonal ORD vs. R&L = 6.16 (5.00–7.58)]. Community-level factors associated with late-stage Hodgkin lymphoma were greater Black (OR80–100% = 1.83; 95% CI = 1.11–3.02) and Hispanic (OR60–79% = 1.30; 95% CI = 1.05–1.60) dissimilarity indices. Late-stage diagnosis for RMS was associated with more redlined census tracts within counties (OR = 1.54; 95% CI = 1.02–2.35) and low/very low Child Opportunity Index (OR = 1.21; 95% CI = 1.02–1.45).

Conclusions:

Novel markers of community deprivation, such as redlining and racial segregation, were correlated with cancer outcomes for children with Hodgkin lymphoma and RMS in this first disparities study using Children’s Oncology Group registries.

Impact:

The interplay of multilevel risk factors provides important consideration for efforts to improve early detection of pediatric cancer diagnosis.
Supplementary Table S2 from CD70-Targeted Allogeneic CAR T-Cell Therapy for Advanced Clear Cell Renal Cell Carcinoma
Authors: Pal Sumanta K. , Tran Ben , Haanen John B.A.G. , Hurwitz Michael E. , Sacher Adrian , Tannir Nizar M. , Budde Lihua E. , Harrison Simon J. , Klobuch Sebastian , Patel Sagar S. , Meza Luis , Dequeant Mary-Lee , Ma Anna , He Qiuling Ally , Williams Leah M. , Keegan Alissa , Gurary Ellen B. , Dar Henia , Karnik Sushant , Guo Changan , Heath Heidi , Yuen Rachel R. , Morrow Phuong K. , Agarwal Neeraj , Srour Samer A.
Published: July 2024

Flow Cytometry Antibody Panel
Supplementary Figure S4 from CD70-Targeted Allogeneic CAR T-Cell Therapy for Advanced Clear Cell Renal Cell Carcinoma
Authors: Pal Sumanta K. , Tran Ben , Haanen John B.A.G. , Hurwitz Michael E. , Sacher Adrian , Tannir Nizar M. , Budde Lihua E. , Harrison Simon J. , Klobuch Sebastian , Patel Sagar S. , Meza Luis , Dequeant Mary-Lee , Ma Anna , He Qiuling Ally , Williams Leah M. , Keegan Alissa , Gurary Ellen B. , Dar Henia , Karnik Sushant , Guo Changan , Heath Heidi , Yuen Rachel R. , Morrow Phuong K. , Agarwal Neeraj , Srour Samer A.
Published: July 2024

CTX131 construct
Supplementary Figure S8 from Randomized Placebo-Controlled, Biomarker-Stratified Phase Ib Microbiome Modulation in Melanoma: Impact of Antibiotic Preconditioning on Microbiome and Immunity
Authors: Glitza Isabella C. , Seo Yongwoo David , Spencer Christine N. , Wortman Jennifer R. , Burton Elizabeth M. , Alayli Farah A. , Loo Christopher P. , Gautam Shikha , Damania Ashish , Densmore Julie , Fairchild Justin , Cabanski Christopher R. , Wong Matthew C. , Peterson Christine B. , Weiner Brian , Hicks Nathan , Aunins John , McChalicher Christopher , Walsh Emily , Tetzlaff Michael T. , Hamid Omid , Ott Patrick A. , Boland Genevieve M. , Sullivan Ryan J. , Grossmann Kenneth F. , Ajami Nadim J. , LaVallee Theresa , Henn Matthew R. , Tawbi Hussein A. , Wargo Jennifer A.
Published: July 2024

Ruminococcaceae family abdunance over time by stratification and arm
Supplementary Table S4 from Efficacy and Safety of Adagrasib plus Cetuximab in Patients with KRASG12C-Mutated Metastatic Colorectal Cancer
Authors: Yaeger Rona , Uboha Nataliya V. , Pelster Meredith S. , Bekaii-Saab Tanios S. , Barve Minal , Saltzman Joel , Sabari Joshua K. , Peguero Julio A. , Paulson Andrew Scott , Jänne Pasi A. , Cruz-Correa Marcia , Anderes Kenna , Velastegui Karen , Yan Xiaohong , Der-Torossian Hirak , Klempner Samuel J. , Kopetz Scott E.
Published: July 2024

Table S4. Overall efficacy summary with adagrasib monotherapy in previously treated patients with KRASG12C-mutated unresectable or metastatic CRCa.
Identification and Characterization of Chemotherapy-Resistant High-Risk Neuroblastoma Persister Cells
Authors: Grossmann Liron D. , Chen Chia-Hui , Uzun Yasin , Thadi Anusha , Wolpaw Adam J. , Louault Kevin , Goldstein Yael , Surrey Lea F. , Martinez Daniel , Calafatti Matteo , Gerelus Mark , Gao Peng , Lee Lobin , Patel Khushbu , Kaufman Rebecca S. , Shani Guy , Farrel Alvin , Moshitch-Moshkovitz Sharon , Grimaldi Paris , Shapiro Matthew , Kendsersky Nathan M. , Lindsay Jarrett M. , Casey Colleen E. , Krytska Kateryna , Scolaro Laura , Tsang Matthew , Groff David , Matkar Smita , Kalna Josh R. , Mycek Emily , McDevitt Jayne , Runbeck Erin , Patel Tasleema , Bernt Kathrin M. , Asgharzadeh Shahab , DeClerck Yves A. , Mossé Yael P. , Tan Kai , Maris John M.
Published: July 2024

Relapse rates in high-risk neuroblastoma remain exceedingly high. The malignant cells that are responsible for relapse have not been identified, and mechanisms of therapy resistance remain poorly understood. In this study, we used single-nucleus RNA sequencing and bulk whole-genome sequencing to identify and characterize the residual malignant persister cells that survive chemotherapy from a cohort of 20 matched diagnosis and definitive surgery tumor samples from patients treated with high-risk neuroblastoma induction chemotherapy. We show that persister cells share common mechanisms of chemotherapy escape, including suppression of MYC(N) activity and activation of NFκB signaling, and the latter is further enhanced by cell–cell communication between the malignant cells and the tumor microenvironment. Overall, our work dissects the transcriptional landscape of cellular persistence in high-risk neuroblastoma and paves the way to the development of new therapeutic strategies to prevent disease relapse.

Significance: Approximately 50% of patients with high-risk neuroblastoma die of relapsed refractory disease. We identified the malignant cells that likely contribute to relapse and discovered key signaling pathways that mediate cellular persistence. Inhibition of these pathways and their downstream effectors is postulated to eliminate persister cells and prevent relapse.

See related commentary by Wolf et al., p. 2308
Supplementary Table 1 from Inhibition of Notch4 Using Novel Neutralizing Antibodies Reduces Tumor Growth in Murine Cancer Models by Targeting the Tumor Endothelium
Authors: Eng Jason W.-L. , Kato Yu , Adachi Yusuke , Swaminathan Bhairavi , Naiche L.A. , Vadakath Rahul , Sakamoto Yoshimasa , Nakazawa Youya , Tachino Sho , Ito Ken , Abe Takanori , Minoshima Yukinori , Hoshino-Negishi Kana , Ogasawara Hideaki , Kawakatsu Tomomi , Nishimura Miyuki , Katayama Masahiko , Shimizu Masashi , Tahara Kazuhiro , Sato Toshitaka , Suzuki Katsuhisa , Agarwala Kishan , Iwata Masao , Nomoto Kenichi , Ozawa Yoichi , Imai Toshio , Funahashi Yasuhiro , Matsui Junji , Kitajewski Jan
Published: July 2024

List of constructs developed and used for experiments including Notch 1-4 expression constructs and the Notch luciferase reporter construct.
Figure 3 from Inhibition of Notch4 Using Novel Neutralizing Antibodies Reduces Tumor Growth in Murine Cancer Models by Targeting the Tumor Endothelium
Authors: Eng Jason W.-L. , Kato Yu , Adachi Yusuke , Swaminathan Bhairavi , Naiche L.A. , Vadakath Rahul , Sakamoto Yoshimasa , Nakazawa Youya , Tachino Sho , Ito Ken , Abe Takanori , Minoshima Yukinori , Hoshino-Negishi Kana , Ogasawara Hideaki , Kawakatsu Tomomi , Nishimura Miyuki , Katayama Masahiko , Shimizu Masashi , Tahara Kazuhiro , Sato Toshitaka , Suzuki Katsuhisa , Agarwala Kishan , Iwata Masao , Nomoto Kenichi , Ozawa Yoichi , Imai Toshio , Funahashi Yasuhiro , Matsui Junji , Kitajewski Jan
Published: July 2024

6-3-A6 treatment alone or in combination with other chemotherapeutic agents delays tumor growth in human tumor xenografts. A, IF staining of Notch4 (red) and CD31+ tumor vessels (green) in additional human tumor xenografts. B, SEKI melanoma human xenografts treated with 6-3-A6 alone, i.v. bevacizumab alone, or lenvatinib alone (n = 5). C, DU145 prostate xenografts treated with i.v. 6-3-A6, i.v. paclitaxel, or combination (n = 4 mice/group). All treatments started 12 hours after tumor implantation. Statistical analysis performed with two-way ANOVA for tumor growth curves, plotted as average ± SEM; *, P < 0.05; **, P < 0.005; ***, P < 0.001.
Effectiveness of Myo-Inositol on Oocyte and Embryo Quality in Assisted Reproduction: Systematic Review and Meta-Analysis of Randomized Clinical Trials
Authors: Pivazyan Laura , Krylova Ekaterina , Obosyan Lilia , Seregina Valeriia , Shapovalenko Roman , Ayryan Eduard
Published: July 2024

Introduction: We sought to conduct a systematic review and meta-analysis of randomized clinical trials (RCTs) to evaluate the impact of myo-inositol on oocyte and embryo quality in women undergoing assisted reproduction. Methods: The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 checklist (registration number: CRD42023433328). Studies were identified by searching PubMed, Cochrane Library, Google Scholar, Scopus, Embase, and ClinicalTrials databases. Results: Eight RCTs were included for qualitative analysis reporting on 820 participants. Four meta-analyses were performed. Numbers of retrieved oocytes in comparison of intervention and control group were higher in inositol group (mean difference [MD] = 0.41, 95% CI: 0.05–0.77, p = 0.02). Meta-analysis of two studies comparing numbers of oocytes among poor ovarian responder patients showed no significant difference between intervention and control group (MD = 0.50, 95% CI: 0.57–1.58, p = 0.36). Miscarriage rate has no statistically significant difference between the treatment and control groups (risk ratios [RRs] = 0.81, 95% CI: 0.20–3.32, p = 0.77). Inositol played no role in improving clinical pregnancy rates; there was no significant difference between the intervention group and the control group (RR = 1.41, 95% CI: 0.88–2.25, p = 0.15). Conclusion: Thus, we did not find any benefits of using myo-inositol on oocyte and embryo quality in women undergoing reproductive technologies. Further studies are needed to assess efficacy, safety, and high compliance by female patients.
Impact of the COVID-19 Pandemic on Acute Stroke Rehabilitation in Japanese Primary Stroke Centers: A Nationwide Cross-Sectional Study Using a Web-Based Questionnaire Survey
Authors: Oyama Naoki , Oki Koichi , Nakajima Makoto , Matsumoto Koichi , Omori Tomohiro , Hayase Makoto , Ohta Tsuyoshi , Koga Masatoshi , Koyama Tetsuo , Fujimoto Shigeru , Iguchi Yasuyuki , Kakuda Wataru , Ogasawara Kuniaki ,   Project Team for the Equalization and Standardization of Acute Stroke Rehabilitation
Published: July 2024

Introduction: Acute stroke rehabilitation is crucial for achieving good functional recovery, even during the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to clarify the impact of the COVID-19 pandemic on acute stroke rehabilitation and identify which components in the acute stroke rehabilitation provision system were susceptible to the pandemic. Methods: A web-based questionnaire survey was conducted in all primary stroke centers (PSCs) in Japan between February 7 and April 21, 2022. The survey included questions about the current status of acute stroke rehabilitation and the influence of the pandemic. We classified the influences and investigated the relationship between the influence of the pandemic and the provision of rehabilitation. Additionally, we investigated a group of prefectures divided according to the grade of the pandemic. Results: The survey response rate was 67% (639 of 959 PSCs). Among them, 387 PSCs (61%) reported that the COVID-19 pandemic affected acute stroke rehabilitation. In PSCs affected by the pandemic, more rehabilitation-related staff were working, and the proportion of weekend/holiday rehabilitation implementation was higher compared to those unaffected. In PSCs from highly infected prefectures, no significant relationship was observed between the influence of the pandemic and the rehabilitation provision system. Conclusions: PSCs that provide denser acute stroke rehabilitation may be affected to a greater extent by the pandemic. We conclude that stroke hospitals should formulate infection control procedures for acute stroke rehabilitation in advance, depending on the conditions of the region and facility.
Efficacy of Donor-Recipient-Matched Faecal Microbiota Transplantation in Patients with IBS-D: A Single-Centre, Randomized, Double-Blind Placebo-Controlled Study
Authors: Zhang Yanli , Wang Shuai , Wang Huifen , Cao Man , Wang Miao , Zhang Bangzhou , Xiao Chuanxing , Zhu Huiting , Du Shiyu
Published: July 2024

Introduction: The imbalance in gut microbiota is contributing to the development and progression of IBS. FMT can improve the gut microbiota, and donor-recipient-matched FMT can help develop individualized treatment plans according to different enterotypes. This study aimed to explore the efficacy of donor-recipient-matched FMT in IBS with predominant diarrhoea (IBS-D) and evaluate its effects on gut microbiota. Methods: Twenty-seven patients with IBS-D were randomly divided into donor-recipient-matched FMT group (group P), random-donor FMT group (group R), and placebo group (group B). All participants received corresponding FMT treatment after filling in IBS-S, IBS-QoL, GSRS, and HADS questionnaires and having their stool samples collected at 4, 8, and 12 weeks after treatment. The improvement in the symptoms and the changes in the bacterial flora were analysed for three groups. Results: The IBS-SSS, IBS-QoL, GSRS, and anxiety scores of group P were significantly lower after treatment (p < 0.05). The IBS-QoL scores of group R were significantly lower after treatment (p < 0.05). Beta diversity analysis showed that the gut microbiota of group P had an obvious trend of classification after treatment. Seven bacterial genera were related to the differences in the IBS-SSS scores before and after treatment. Conclusion: Donor-recipient-matched FMT significantly improved the clinical symptoms, quality of life, and anxiety scores of the patients with IBS-D than random-donor FMT.
Retropharyngeal Abscess Complicated by Mediastinitis in Infants
Authors: Thomas Ann , Adam Shaun , Goussard Pierre , Venkatakrishna Shyam Sunder B. , Andronikou Savvas , Grobbelaar Johan
Published: July 2024

Introduction: Most paediatric upper respiratory infections are virally mediated and result in self-limiting reactive lymphadenopathy. In children younger than 5 years, retropharyngeal lymph nodes may give rise to deep neck space infections in this potential space. Retropharyngeal infections are rare after 5 years because lymph nodes undergo atrophy. Methods: We present a series of 6 cases of paediatric retropharyngeal abscesses (RPA) complicated by mediastinitis, managed at a tertiary hospital over a 4-year period. Results: All our cases presented with fever, difficulty feeding, and neck swelling. The age range was 11 weeks–11 months, and all tested negative for human immunodeficiency virus. The diagnosis and complications were confirmed on computed tomography (CT) scan. The CT scans consistently revealed RPA with varying degrees of deep neck space and mediastinal extension. All children were promptly taken to theatre for source control. Two were extubated successfully immediately after surgery, and the other 4 were extubated in the paediatric intensive care unit, with the longest duration of intubation being 3 days. Methicillin-sensitive Staphylococcus aureus (MSSA) was cultured in all 6 cases. Conclusion: Management of these cases may be challenging, and young children with RPA require close care and airway monitoring. CT or magnetic resonance imaging is essential to delineate the extent of infection. Surgical drainage should be performed when there is a large abscess, a complication occurs, or an inadequate response in 24–48 h to medical management.
Extraskeletal Ewing Sarcoma of the Extremities and Trunk: A Retrospective Analysis of a Mono-Institutional Series
Authors: Bianchi Giuseppe , Laginestra Maria Antonella , Simonetti Elisa , Ibrahim Toni , Macrì Fabiana , Ostetto Federico , Tuzzato Gianmarco , Paioli Anna , Gambarotti Marco , Cocchi Stefania , Donati Davide Maria , Scotlandi Katia , Laranga Roberta
Published: July 2024

Introduction: Extraskeletal Ewing sarcoma (EEwS) is a rare malignant tumor, and current international recommendations indicate systemic and local treatment like bone Ewing sarcoma (BEwS); to the best of our knowledge, very few studies tried to explore the clinical and genetic characteristics of this tumor, and the most appropriate treatment strategy remains uncertain. Methods: We reviewed 35 EEwS cases enrolled at Rizzoli Orthopedic Institute in Bologna, Italy, between 1988–2022. We performed RNA sequencing in 18 Ewing sarcoma cases, including 12 BEwSs and 6 EEwSs. We analyzed overall survival (OS), local relapse-free survival (LRFS), and metastasis-free survival (MFS) and the risk factors associated to survival. Results: Unsupervised hierarchical clustering showed no differences in the transcriptional profile between EEwS and BEwS. Five-year OS was 67% (95% confidence interval [CI]: 47–80), 5-year LRFS was 61% (95% CI: 43–75), and 5-year MFS was 55% (95% CI: 38–70). Recurrent tumors, larger than 8 cm, and elevated lactate dehydrogenase (LDH) serum value resulted to be negative prognostic factors. Conclusions: The finding/detection of a genetic profile that is indistinguishable between EEwS and BEwS confirms the view that the two subgroups belong to the same tumor entity and supports the use of a single therapeutic approach for Ewing sarcoma, regardless of the site of origin. Statistical evaluation showed that size bigger than 8 cm, elevated LDH, and recurrent tumors had a worse prognosis, suggesting a risk-stratification method for identifying patients for specific therapy treatment. However, larger, multicenter, prospective trials are called for to validate our findings.
A hybrid gradient climbing algorithm for a swarm robot-based gas leak detector
Authors: Adegunsoye Adeola Erastus , Ubochi Brendan , Macaulay John , Akingbade Kayode Francis
Published: July 2024

Methane emissions from leak sources can have a negative climate impact, in addition to contributing to the risk of explosions in urban environments. These risks can be minimized by developing systems that provide for an accurate and timely detection and localization of a gas leakage point. This research used a swarm of robots to detect and locate a leakage point. The localization algorithm derives from further optimization of the gradient climbing algorithm using fireflies acting as opportunistic agents. Firefly agents are characterized by their bioluminescent communication which guides them to dynamically adjust their positions and intensities based on the quality of the gradient information available to them. The proposed research focuses on enhancing gas leak detection through the development of a hybrid gradient climbing algorithm. This algorithm integrates gradient climbing techniques with swarm intelligence, utilizing the strengths of both approaches. This simulation resulted in the hybrid algorithm leading to a reduced convergence time and path lengths when compared to the swarm without opportunistic agents. The suggested approach can be important especially in gas distribution systems or in areas where human intervention is considered to be unsafe.
ESKİ TÜRKLERDE VATAN ANLAYIŞININ DEVLET YÖNETİMİ, SOSYAL HAYAT VE HUKUKİ AÇIDAN DEĞERLENDİRİLMESİ
Authors: Mandaloğlu Mehmet
Published: July 2024

Eski Türklerde devletin temelini halk, istiklal, ülke ve töre oluşturmaktadır. Teşkilatlı bir yapıya sahip olan Türkler sahip oldukları toprakları vatan hâline getirmişler ve siyasi organizasyonlar kurmuşlardır. Eski Türkler, toprağın kutsallığını ifade etmek için “vatan” kavramını kullanmışlardır. Devlet arazisi olan ülke toprakları, Türklerde bölünmez bir bütündür. Türklerde devletin temeli aileye dayanmaktadır. Vatan toprakları, ailenin ve devletin bağımsız yaşamını sürdürdüğü mekânıdır. Bundan dolayı vatan toprakları, Türklerde kutsal kabul edilmiştir. Çalışmanın amacı, vatan anlayışının eski Türk devlet ve toplum hayatında önemli olduğunu ortaya koymaktır. Bu bağlamda öncelikle eski Türklerde vatan kavramı üzerinde durulmuş ve devletin varlığını sürdürmesinin vatan toprakları ile mümkün olduğu ifade edilmiştir. Daha sonra vatan anlayışının eski Türk devlet yönetimi, sosyal hayat ve hukuki açıdan değerlendirilmesi yapılmıştır. Çalışmada aynı zamanda devleti oluşturan unsurlardan birinin vatan olduğu ve kutsal kabul edildiği vurgulanmıştır.
Birinci Dünya Savaşı Sonrası Avusturya Cumhuriyeti’nde Millî Kimlik İnşası (1919-1938)
Authors: Yücel Gökberk , Doğan Fatih
Published: July 2024

Avusturyalı kimdir? Avusturyalı kimliğinin terkibinde hangi unsurlar ön plana çıkmıştır? Etnik ya da din merkezli bir aidiyet midir yoksa siyasî bir mensubiyete ve iradeye mi müstenittir? Bu çalışma, kıta Avrupası’nın son çok uluslu imparatorluğu Avusturya-Macaristan Devleti’nin dağılışı sonrası kurulan Birinci Avusturya Cumhuriyeti’de millî kimlik inşasının politik sürecini ve bu süreç içerisinde milliyetçiliğin çatallaşan yollarını ihtiva etmektedir. Yoğunluklu olarak Almanca literatürün tarandığı çalışma, kavramsal olarak milliyetçiliğin ulusal kimlik politikaları ile sınırlandırılmıştır; bilvesile çalışmada Avusturya Cumhuriyeti’nin kuruluş yılı ile Nazi Almanya’sının ilhakı arası dönem incelenmiştir. Birinci Cihan Harbi sonrasında Avusturya’da milliyetçilik, sosyal demokratların ekonomik sebeplerle Almanya’yla birleşme motivasyonu bağlamında panist-bütünleşmeci anlayışla melezleşmiştir. 1930ların başında ise milliyetçilik, ideolojik mutasyona uğrayarak klerikal faşizme dönüşmüştür.
II. Karabağ Savaşı’nda Türkiye’nin Jeostratejik Rolü: Karasal Mekanda Devlet Düzeyinde Etki Analizi
Authors: Özveren Mustafa
Published: July 2024

Stratejinin coğrafi boyutu, ulusal çıkarların korunması açısından belirli değişkenlere sahiptir. Bu
değişkenler, jeostratejinin analizi için kategorizasyon imkanı sunmaktadır. Bu çalışma, Türkiye’nin II. Karabağ
Savaşı’ndaki jeostratejik rolünü analiz etmeyi amaçlamaktadır. Bu doğrultuda karasal mekan niteliği ve devlet
düzeyinde etki kapasitesi kategorizasyonu çerçevesinde bir inceleme gerçekleştirilmektedir. Çalışma, nitel
yöntemle analitik bir genellemeyi hedeflemektedir. Jeostratejinin teorik ve kavramsal altyapısı üzerine örnek
olayın bu altyapıdaki yeri sorgulanmaktadır. Karabağ Sorunu temelde Azerbaycan ve Ermenistan arasında
yaşanan bir sorun olsa dahi bölgesel etkileri bakımından Türkiye için önemli sonuçlar doğurmaktadır. Bu
nedenle çalışma, akademik ve siyasi perspektifin keskinleştirilmesine ve belirgin sınırlar çizilmesine katkı
sunmayı hedeflemektedir. Bu ışıkta Türkiye’nin II. Karabağ Savaşı’ndaki jeostratejik rolü; kara savaşını
etkileyen stratejik hamleler, enerji kaynakları ve erişim güzergahları, ticaret hacmi ve rotaları, coğrafi açıdan
stratejik noktalar ve sınır komşuları kategorizasyonu ile analiz edilmektedir.
Apiturizmin Gelişmesinde Arıcılık Müzelerinin Önemi: Çine Arıcılık Müzesi ve Eğitim Merkezi Üzerine Bir Değerlendirme
Authors: Akıncı Ekiztepe Burçak
Published: July 2024

Bu çalışmada Çine ve yöresinde apiturizmin gelişmesinde Çine Arıcılık Müzesi ve Eğitim Merkezi’nin katkısı araştırılmıştır. Araştırma çerçevesinde öncelikle apiturizm, gelişim süreci, Dünya’da ve Türkiye’de örnek uygulamalar üzerine kapsamlı bir literatür araştırması yapılmıştır. Yapılandırılmamış alan çalışması veri toplama aracı olarak kullanılmış, katılımcı gözlemci olarak olgunun ayrıntılı bir şekilde tanımlanabilmesi amacıyla gözlem ve inceleme yapılmıştır. Öncelikle müze yetkilisi ile görüşülmüş, ardından tesadüfi olmayan örnekleme yöntemlerinden olan kartopu örnekleme yöntemi ile konuyla ilgili bilgi sahibi kişi veya kişilerin kim olabileceği öğrenilmiş, oluşturulan 14 soruluk görüşme formu yöre hakkında bilgi sahibi olan kişilere yöneltilerek mülakat tekniği kullanılmıştır. Araştırma sonucunda apiturizmin Çine ve yöresinde henüz uygulanan bir turizm türü olmadığı ancak gelişmeye uygun olduğu belirlenmiştir.
Assemblage Robotic Plants: Individualizations of Many Orders of Magnitude
Authors: Bergamo Marilia Lyra
Published: July 2024

This paper focuses on the author’s artistic practice and presents robotic plant creations as assemblages using robotic autonomy unities in a Small-World Network configuration. This artistic production is significantly founded on Gilbert Simondon’s philosophical concepts about Technological Beings. Understanding these communities of robotic structures as individualizations is critical to apprehending them as individuals. The paper also discusses the implications of hardware design, coding, and the concept of artificial life related to the development of such technological organisms.
The Provenance of the “Seiyal Collection”
Authors: Press Michael
Published: July 2024

This article considers the collection history of the so-called “Seiyal Collection,” purchased by the Palestine Archaeological Museum in 1952 and 1953. While the Taʿamireh Bedouin and/or Khalil Iskander Shahin reported the material as coming from Wadi Seiyal, much if not all of the material was actually looted from caves in Nahal Hever. The common claim that the Bedouin misreported the findspot to hide the fact that they had smuggled the material from Israel into then-Jordanian-held East Jerusalem cannot be correct, as the caves along both Wadi Seiyal and Nahal Hever are on the Israeli side of the Green Line. The article considers why the provenance was misreported, whether the scrolls team knew that the material had been smuggled from Israel, and the implications of these issues both for our understanding of the scrolls and for scholarly ethics.