bluuebunny/crossref_metadata_2025 huggingface dataset:
Learning to Optimize LSM-trees: Towards A Reinforcement Learning based Key-Value Store for Dynamic Workloads
Authors: Mo Dingheng , Chen Fanchao , Luo Siqiang , Shan Caihua
Published: November 2023

LSM-trees are widely adopted as the storage backend of key-value stores. However, optimizing the system performance under dynamic workloads has not been sufficiently studied or evaluated in previous work. To fill the gap, we present RusKey, a key-value store with the following new features: (1) RusKey is a first attempt to orchestrate LSM-tree structures online to enable robust performance under the context of dynamic workloads; (2) RusKey is the first study to use Reinforcement Learning (RL) to guide LSM-tree transformations; (3) RusKey includes a new LSM-tree design, named FLSM-tree, for an efficient transition between different compaction policies -- the bottleneck of dynamic key-value stores. We justify the superiority of the new design with theoretical analysis; (4) RusKey requires no prior workload knowledge for system adjustment, in contrast to state-of-the-art techniques. Experiments show that RusKey exhibits strong performance robustness in diverse workloads, achieving up to 4x better end-to-end performance than the RocksDB system under various settings.
Identifying Relationships and Classifying Western-style Paintings: Machine Learning Approaches for Artworks by Western Artists and Meiji-era Japanese Artists
Authors: Vinayavekhin Phongtharin , Khomkham Banphatree , Suppakitpaisarn Vorapong , Codognet Phillippe , Terada Torahiko , Miura Atsushi
Published: November 2023

Many Western-style paintings by Japanese artists in the early 1900s, though maintaining a unique quality, were greatly inspired by the works of Western artists. In this article, we employ machine learning to identify relationships and classify the works of Japanese and Western artists. The relationships are of significant interest to numerous art historians, as they can reveal how Western art was introduced to Japan. Historically, art historians have manually annotated these correspondences, which is a time-consuming and labor-intensive process. In this article, we introduce a new method for finding correspondences between related artworks by comparing their overall outline information. This technique is based on Siamese neural networks (SNNs) and a self-supervised learning approach. Additionally, we have compiled a dataset of illustrations from Japanese artists such as Seiki Kuroda and Western artists such as Raphaël Collin, complete with correspondence annotations. However, to exhibit the unique quality of works by Japanese artists, we demonstrate that machine learning can classify between artworks created by Japanese artists and those created by Western artists.
Supervised Hierarchical Online Hashing for Cross-modal Retrieval
Authors: Han Kai , Liu Yu , Wei Rukai , Zhou Ke , Xu Jinhui , Long Kun
Published: November 2023

Online cross-modal hashing has gained attention for its adaptability in processing streaming data. However, existing methods only define the hard similarity between data using labels. This results in poor retrieval performance, as they fail to exploit the semantic structure information of labels and miss the high-quality hash codes guided by the hierarchical relevance between labels. In addition, they ignore the bit-flipping problem, which leads to sub-optimal cross-modal retrieval performance. To address these issues, we propose Supervised Hierarchical Online Hashing (SHOH) for cross-modal retrieval. Our approach acquires hierarchical similarity via cross-layer affiliation of labels and explores its application to online hashing. We design a hierarchical similarity learning method in the online learning framework, which includes virtual center learning and hierarchical similarity embedding. Labels with soft similarity bridge the label hierarchy and cross-modal hash embedding. Furthermore, we propose a Weighted Retrieval Strategy (WRS) to mitigate the impact caused by bit-flipping errors. Extensive experiments and verification on hierarchical and non-hierarchical datasets demonstrate that SHOH preserves accurate inter-class distances and achieves performance improvements compared to state-of-the-art methods. The source code is available at
https://github.com/HUST-IDSM-AI/SHOH
.
Investigating Participation Mechanisms in EU Code Week
Authors: Sirocchi Christel , Ostergren Annika Pofantis , Bogliolo Alessandro
Published: November 2023

Digital competence (DC) is a broad set of skills, attitudes, and knowledge for confident, critical, and responsible use of digital technologies in every aspect of life. DC proves essential in the contemporary digital landscape, yet its diffusion is hindered by biases, misunderstandings, and limited awareness. Teaching Informatics in the educational curriculum is increasingly supported by the institutions but faces serious challenges, such as teacher upskilling and support. In response, grassroots movements promoting computing literacy in an informal setting have grown, including EU Code Week, whose vision is to develop computing skills while promoting diversity and raising awareness of the importance of digital skills. This study extensively analyses EU Code Week editions spanning 2014 to 2021 across European Union member states, pursuing three primary objectives: firstly, to evaluate teacher engagement in the campaign in terms of penetration, retention, and spatial distribution; secondly, to characterise the multifaceted audience and themes embraced by these initiatives; and, lastly, to investigate the influence of socio-economic factors on engagement. The investigation uncovers the underlying mechanisms fostering Code Week’s engagement, providing insights to campaign organisers for strategic planning and resource allocation in future editions. Moreover, the analysis reveals that the most engaged areas are characterised by lower income as well as lower digital literacy, restricted access to technology, and a less established computer education, suggesting that Code Week thrives precisely where its impact is most needed.
Vision Transformer Inspired Automated Vulnerability Repair
Authors: Fu Michael , Nguyen Van , Tantithamthavorn Chakkrit , Phung Dinh , Le Trung
Published: November 2023

Recently, automated vulnerability repair approaches have been widely adopted to combat increasing software security issues. In particular, transformer-based encoder-decoder models achieve competitive results. Whereas vulnerable programs may only consist of a few vulnerable code areas that need repair, existing AVR approaches lack a mechanism guiding their model to pay more attention to vulnerable code areas during repair generation. In this article, we propose a novel vulnerability repair framework inspired by the Vision Transformer based approaches for object detection in the computer vision domain. Similar to the object queries used to locate objects in object detection in computer vision, we introduce and leverage vulnerability queries (VQs) to locate vulnerable code areas and then suggest their repairs. In particular, we leverage the cross-attention mechanism to achieve the cross-match between VQs and their corresponding vulnerable code areas. To strengthen our cross-match and generate more accurate vulnerability repairs, we propose to learn a novel vulnerability mask (VM) and integrate it into decoders’ cross-attention, which makes our VQs pay more attention to vulnerable code areas during repair generation. In addition, we incorporate our VM into encoders’ self-attention to learn embeddings that emphasize the vulnerable areas of a program. Through an extensive evaluation using the real-world 5,417 vulnerabilities, our approach outperforms all of the automated vulnerability repair baseline methods by 2.68% to 32.33%. Additionally, our analysis of the cross-attention map of our approach confirms the design rationale of our VM and its effectiveness.
Finally, our survey study with 71 software practitioners highlights the significance and usefulness of AI-generated vulnerability repairs in the realm of software security.
The training code and pre-trained models are available at https://github.com/awsm-research/VQM.
Caveolin-1 forms a complex with P2X7 receptor and tunes P2X7-mediated ATP signaling in mouse bone marrow-derived macrophages
Authors: Sawai Yuuki , Suzuki Yoshiaki , Asagiri Masataka , Hida Shigeaki , Kondo Rubii , Zamponi Gerald W. , Giles Wayne R. , Imaizumi Yuji , Yamamura Hisao
Published: November 2023

In bone marrow-derived macrophages, Cav-1 suppresses the macropore formation of P2X7 receptors through their direct or indirect interactions, resulting in reduced membrane permeability of cations (Ca2+ and K+) and large cell-impermeable dye (TO-PRO3) induced by ATP. Cav-1 also inhibits ATP-induced IL-1β secretion, ROS production, GSDMD cleavage, and pyroptosis. Cav-1 contributes to the maintenance of proper immune responses by finely tuning IL-1β secretion and cell death in macrophages.
Cytoprotective E-WE thrombin reduces disease severity in a murine model of relapsing-remitting multiple sclerosis
Authors: Verbout Norah G. , Su Weiping , Pham Peter , Jordan Kelley R. , Kohs Tia C. L. , Tucker Erik I. , McCarty Owen J. T. , Sherman Larry S.
Published: November 2023

There are limited treatment options for mitigating acute relapsing attacks for patients with multiple sclerosis. We tested the hypothesis that harnessing the cytoprotective activity of the blood coagulation enzyme, thrombin, would provide benefit and protection against relapsing disease in a mouse model of MS. Our results provide rationale for considering engineered forms of thrombin biased toward cytoprotective activity as a therapeutic strategy and perhaps an alternative to steroids for the management of relapsing MS attacks.
Transcriptomic changes in glomeruli in response to a high salt challenge in the Dahl SS rat
Authors: Semenikhina Marharyta , Lysikova Daria V. , Spires Denisha R. , Domondon Mark , Stadler Krisztian , Palygin Oleg , Ilatovskaya Daria V.
Published: November 2023

Our study demonstrated novel pathways affecting glomeruli under stress induced by dietary salt. Predictive gene correlation networks and bioinformatic semi-automatic analysis revealed changes in the pathways relevant to mitochondrial function, inflammatory, apoptotic/fibrotic processes, and cell calcium transport.
Hydrogel-Loaded Exosomes: A Promising Therapeutic Strategy for Musculoskeletal Disorders
Authors: Zhang Chunyu , Zhou Xuchang , Wang Dongxue , Hao Li , Zeng Zhipeng , Su Lei
Published: November 2023

Clinical treatment strategies for musculoskeletal disorders have been a hot research topic. Accumulating evidence suggests that hydrogels loaded with MSC-derived EVs show great potential in improving musculoskeletal injuries. The ideal hydrogels should be capable of promoting the development of new tissues and simulating the characteristics of target tissues, with the properties matching the cell-matrix constituents of autologous tissues. Although there have been numerous reports of hydrogels loaded with MSC-derived EVs for the repair of musculoskeletal injuries, such as intervertebral disc injury, tendinopathy, bone fractures, and cartilage injuries, there are still many hurdles to overcome before the clinical application of modified hydrogels. In this review, we focus on the advantages of the isolation technique of EVs in combination with different types of hydrogels. In this context, the efficacy of hydrogels loaded with MSC-derived EVs in different musculoskeletal injuries is discussed in detail to provide a reference for the future application of hydrogels loaded with MSC-derived EVs in the clinical treatment of musculoskeletal injuries.
A Systematic Review on Potential Bio Leather Substitute for Natural Leather
Authors: Kefale Girmaw Yeshanbel , Kebede Zerihun Teshome , Birlie Alehegn Atalay
Published: November 2023

Bio-based leather substitutes are an emerging class of ethically and environmentally responsible natural fabrics that are increasingly exceeding consumer aesthetic and functional expectations as an alternative to bovine and synthetic leathers. This literature review creates a clear and elaborative overview of conventional leather processing along with innovative potential bio-leather substitutes. Plant-driven, fungal-origin, bacterial-driven, and animal-origin bio-leathers are the current innovative research advances addressed in this literature. While traditional leather and its alternatives are sourced from animals and synthetic polymers, these renewable and sustainable leather substitutes are gained from bacterial cellulose, mycelium, plant cellulose, and animal cells using tissue engineering and other eco-friendly techniques. In conclusion, bio-based leather alternatives are eco-friendly, non-toxic, and sustainable and ultimately can substitute natural leather made by conventional processing.
Impact of Short-Term Weight Loss on Hemostasis and Thrombosis after Bariatric Surgery
Authors: Taha Ahmed , Eroğlu Hasan , Demirbaş İskender Eren , Demir Berkay , Dilektaşli Evren
Published: November 2023

Introduction. Obesity causes thrombophilia and many coagulation problems related to slowing the capillary flow. We aimed to evaluate rapid weight loss outcomes in the early period after bariatric surgery on the coagulation system. Materials and Method. A prospective study enrolled 28 patients with a BMI > 40 kg/m2 who underwent bariatric surgery. Preoperative and postoperative (first and third months) demographic criteria—such as age, gender, weight, height, and alcohol and tobacco use, and biochemical parameters such as PLT, PT, aPTT, INR, bleeding time, coagulation time, fibrinogen, D-dimer, albumin, calcium, ionized calcium, vitamin D, and PTH—were analyzed. Results. We found that both bleeding and thrombotic parameters increase in early-slowing surgery. The first-month platelet levels were significantly different from the preoperative values (

p

 < 0.001). The prothrombin time in the first (

p

 < 0.001) and third months (

p

 < 0.009) was also comparable. The PTT in the first month was higher than in the preoperative period (

p

 < 0.011). INR in the first month (

p

 < 0.001) was higher than that in the preoperative period and the third month (

p

 = 0.007) value was higher than in the first month. In terms of fibrinogen levels, all parameters indicated statistical significance within each other; preoperative to the first month (

p

 < 0.001), the first month to the third month (

p

 < 0.016). Third-month D-dimer levels were lower than the first month’s values (

p

 = 0.032). Conclusion. Thromboembolic events have crucial importance in the converse scenario of haemorrhagic diathesis during the first months of bariatric surgery. Vitamin support and antithrombotic agents may be recommended in the early postoperative period.
Prevalence and Triggering Factors of Headache among Jordanian Adolescents in Al-Mafraq Region
Authors: Albashtawy Mohammed , Alhroub Nisser , Zafar Zohair , Hamaideh Shaher , Al-Osoufe Laith , Malak Malakeh , Bashtawi Mahmoud , Abdalrahim Asem , Rayan Ahmad , Albashtawy Sa’d , Alkhawaldeh Abdullah , Aljezawi Ma’en , Jallad Mohammed , Abu Khader Imad , Albashtawy Bayan , Al-Kharabsheh Muna
Published: November 2023

Aims. This study evaluates the epidemiology of headache and migraine among adolescents aged 12 to 15. Methods. A school-based cross-sectional study was conducted to collect and analyze data from students in grades 7–10 over the course of one month, using a simple random sampling method. The overall number of participants in this study was 692, with an average age of 13.9 years (SD = 1.3). Descriptive measures and Fisher’s exact test were computed. Multivariate regression was calculated to assess the predictors of headache and migraine. Findings. Approximately one-half of the students reported having headaches: tension-type headaches (10.3%), migraines (4.8%), and other headache types (31.5%). Moreover, girl students in the age group of 14-15 reported more headaches and migraines. Conclusion. The prevalence of headache and migraine in Jordan is high and increasing as students grow older. Health education programs led by school nurses and other healthcare practitioners are urgently needed.
Is Airborne 2,4,6-Trichloroanisole (TCA) a Threat for Bottled Wine?
Authors: Tarasov Andrii , Jung Rainer
Published: November 2023

Background and Aims. This work investigated the TCA permeability of twelve types of commercial bottle closures during 24 months of bottle storage in the d5-TCA-contaminated atmosphere: medium pollution (max. ∼50 ng/L of d5-TCA in the air) and high pollution (max. ∼500 ng/L of d5-TCA in the air). Methods and Results. The d5-TCA content of wine samples and bottle closures was monitored by GC-MS analysis, and the closures of one group (comprising natural corks, agglomerated stoppers, and BVS Tin Saran™ screw caps) were found to be excellent barriers against airborne d5-TCA, i.e., no contaminant was detected in wine under any storage conditions. In contrast, a second group of closures (synthetic stoppers with low OTR, BVS Saranex™, and plastic body screw caps) allowed permeation of d5-TCA, polluting the wine when air contamination was high, albeit no d5-TCA was detected in wines following storage under medium air contamination conditions. A third group of closures (synthetic stoppers with medium and medium + OTR, MCA screw caps, and glass stoppers) allowed d5-TCA to accumulate in wine under both medium and high contamination environments. Conclusions. Some commercial bottle closures were found to permeate airborne d5-TCA, thereby contaminating bottled wine under certain storage conditions. Significance of the Study. This work provides the wine industry with insight into the potential for postbottling contamination of wine by airborne TCA.
Prevalence, Distribution, and Factors Associated with Vector-Borne Pathogen Infections in Pet Dogs from Different Geoclimatic Zones in Sri Lanka
Authors: Atapattu Ushani , Colella Vito , Worsley Andrew , Huggins Lucas G. , Wiethoelter Anke , Traub Rebecca J.
Published: November 2023

Vector-borne pathogens (VBPs) cause significant diseases in dogs in the tropics. In Sri Lanka, the scarce availability of previous studies on canine VBPs has hampered an accurate evaluation of their prevalence in pet dog populations. In this study, we collected demographic, clinical, and environmental data together with whole blood from 423 pet dogs from three geoclimatic zones in Sri Lanka. All blood samples were screened using a previously validated multiplex qPCR assay to detect the six most prevalent canine VBPs in tropical Asia. Multivariable logistic regression models were used to investigate environmental and host factors as predictors of VBP infections. Overall, 254 dogs (60.1%, 95% CI: 55.3–64.6%) were infected with one or more VBPs. Babesia gibsoni was the most prevalent VBP with 37.4% (95% CI: 32.7–42.2%) of dogs infected followed by Hepatozoon canis (21.04%, 95% CI: 17.25–25.24%), haemotropic mycoplasmas (10.2%, 95% CI: 7.5–13.4%), Babesia vogeli (5%, 95% CI: 3.2–7.5%), Ehrlichia canis (4.5%, 95% CI: 2.7–6.9%), and Anaplasma platys (3.8%, 95% CI: 2.12–6.1%). Predictors of VBP infections included tick infestation for H. canis (

p
=
0.05

) and A. platys (

p
=
0.01

), as well as age for B. gibsoni (

p
=
0.01

) and H. canis (

p
=
0.05

) infection. Local breed (

p
=
0.004

), male dogs (

p
=
0.001

) and flea infestation (

p
=
0.04

) were significantly associated with haemotropic mycoplasma infections suggesting direct-blood exchange through fighting and fleas as a possible means of transmission for these pathogens. Clinical results suggest that B. gibsoni and E. canis caused clinically significant disease, especially in exotic breeds such as German shepherds and Rottweilers compared to the local breeds (

p
<
0.001

). Measures such as educating pet dog owners on the importance of being vigilant on ectoparasite infestation of their pets, preventing pet dogs from interacting with stray or community dogs, and the compliant use of effective ectoparasiticides will be crucial for effective control of VBPs in pet dogs in Sri Lanka.
Shrinkage Methods for Estimating the Shape Parameter of the Generalized Pareto Distribution
Authors: Pels Wilhemina Adoma , Adebanji Atinuke O. , Twumasi-Ankrah Sampson , Minkah Richard
Published: November 2023

The generalized Pareto distribution is one of the most important distributions in statistics of extremes as it has wide applications in fields such as finance, insurance, and hydrology. This study proposes two new methods for estimating the shape parameter of the generalized Pareto distribution (GPD). The proposed methods use the shrinkage principle to adapt the existing empirical Bayesian with data-based prior and the likelihood moment method to obtain two estimators. The performance of the proposed estimators is compared with the existing estimators (i.e., maximum likelihood, likelihood moment estimators, etc.) for the shape parameter of the generalized Pareto distribution in a simulation study. The results show that the proposed estimators perform better for small to moderate number of exceedances in estimating shape parameter of the light-tailed distributions and competitive when estimating heavy-tailed distributions. The proposed estimators are illustrated with practical datasets from climate and insurance studies.
Cervical Cancer Screening and Treatment Algorithms Using Human Papillomavirus Testing—Lessons Learnt from a South African Pilot Randomized Controlled Trial
Authors: Sebitloane Hannah M. , Forestier Mathilde , Ginindza Themba G. , Dhlomo Wendy , Moodley-Govender Eshia , Darragh Teresa M. , Baena Armando , Herrero Rolando , Almonte Maribel , Broutet Nathalie , De Vuyst Hugo
Published: November 2023

Background:

To report quantitative and qualitative results on cervical cancer human papillomavirus (HPV)-based screening and treatment algorithms, with/out triage with visual inspection after acetic acid (VIA), followed by ablative treatment (AT).

Methods:

Women 30 to 54 years old from Durban, South Africa were recruited, regardless of human immunodeficiency virus (HIV) status, randomized into one of two study arms and screened for HPV. VIA triage arm: HPV-positive women were triaged using VIA, biopsied and received AT if VIA positive and eligible; no triage arm: eligible HPV-positive women received AT. Women ineligible for AT were referred to colposcopy. Women were asked about side effects immediately and 1 week after AT. Retention to screening and treatment algorithms was compared between arms.

Results:

A total of 350 women [275 HIV-uninfected and 75 women living with HIV, (WLWH)] were allocated to receive HPV testing with VIA triage (n = 175) or no triage (n = 175). HPV prevalence was 28% [95% confidence interval (CI) = 23–33]; WLWH: 52% (95% CI = 40–64) versus HIV-uninfected: 21% (95% CI = 17–27; P < 0.05). Among women who underwent VIA triage with histologic diagnosis, 3/17 were VIA negative with cervical intraepithelial neoplasia (CIN)2+; 14/18 were VIA positive with <CIN2. Retention to screening and treatment algorithms was high (92%).

Conclusions:

This pilot demonstrated the feasibility of implementing screening and treatment algorithms, including performing triage and treatment in one visit; however, VIA triage did not reduce overtreatment and missed some precancerous lesions.

Impact:

This study reports on implementation feasibility of two World Health Organization screening and treatment algorithms (with/out VIA triage). Although the retention to screening and treatment algorithms was high in both arms, the question of how best triaging HPV-positive women deserves further consideration, particularly for WLWH.

See related In the Spotlight, p. 763
Metabolic Syndrome and the Risk of Ductal Carcinoma In Situ of the Breast in the UK Biobank
Authors: Peila Rita , Rohan Thomas E.
Published: November 2023

Background:

Metabolic syndrome (MetS), defined by the presence of three of more metabolic dysregulations such as hyperlipidemia, hyperinsulinemia, central obesity, and hypertension, has been associated with increased risk of cardiovascular disease, diabetes, and various cancers, including invasive breast cancer (IBC). Whether MetS is a risk factor for ductal carcinoma in situ of the breast (DCIS), a nonobligate precursor of IBC, remains unknown.

Methods:

A total of 198,748 women ages 40 to 69 years, DCIS- and IBC-free at enrolment in UK Biobank, were included in the current study. Multivariable-adjusted Cox proportional hazards models were used to estimate the association between MetS and DCIS.

Results:

A total of 1,251 DCIS cases were ascertained during an average follow-up of 11.4 years. There was no association between MetS and the risk of DCIS overall, or by menopausal status. Analysis of individual components of MetS showed an association between central obesity (waist circumference ≥88 cm) and increased DCIS risk in postmenopausal women.

Conclusions:

In this prospective study, we found no association between MetS and DCIS risk.

Impact:

The study findings do not support an association between MetS and this breast cancer precursor.
Facts and Hopes in Neoadjuvant Immunotherapy: Current Approvals and Emerging Evidence
Authors: Vaidya Poorva , Cohen Ezra E.W.
Published: November 2023

In 2021 and 2022, two immune checkpoint inhibitors received FDA approval in the neoadjuvant setting for the treatment of early-stage triple negative breast cancer (TNBC) and non–small cell lung cancer (NSCLC). Several more studies have since indicated the benefits, and challenges, of administering neoadjuvant immunotherapy prior to definitive surgery in the gastrointestinal, head and neck, and cutaneous realms. In addition, numerous ongoing phase II and phase III trials are investigating outcomes of neoadjuvant immune treatment in early-stage disease. As such, it is anticipated that more immune checkpoint inhibitors will receive approval for various neoadjuvant indications in the next several years. Medical oncologists, surgeons, and other providers in a multidisciplinary cancer care team will be presented with alternate treatment paradigms and clinical decisions regarding upfront surgery versus neoadjuvant treatment. Here, we describe the current evidence supporting use of immune checkpoint inhibitors for neoadjuvant treatment, ongoing studies, and clinical considerations of this treatment approach.
High-Fat Diet Promotes Acute Promyelocytic Leukemia through PPARδ-Enhanced Self-renewal of Preleukemic Progenitors
Authors: Mazzarella Luca , Falvo Paolo , Adinolfi Marta , Tini Giulia , Gatti Elena , Piccioni Rossana , Bonetti Emanuele , Gavilán Elena , Valli Debora , Gruszka Alicja , Bodini Margherita , Gallo Barbara , Orecchioni Stefania , de Michele Giulia , Migliaccio Enrica , Duso Bruno A. , Roerink Sophie , Stratton Mike , Bertolini Francesco , Alcalay Myriam , Dellino Gaetano Ivan , Pelicci Pier Giuseppe
Published: November 2023

Risk and outcome of acute promyelocytic leukemia (APL) are particularly worsened in obese-overweight individuals, but the underlying molecular mechanism is unknown. In established mouse APL models (Ctsg-PML::RARA), we confirmed that obesity induced by high-fat diet (HFD) enhances leukemogenesis by increasing penetrance and shortening latency, providing an ideal model to investigate obesity-induced molecular events in the preleukemic phase. Surprisingly, despite increasing DNA damage in hematopoietic stem cells (HSC), HFD only minimally increased mutational load, with no relevant impact on known cancer-driving genes. HFD expanded and enhanced self-renewal of hematopoietic progenitor cells (HPC), with concomitant reduction in long-term HSCs. Importantly, linoleic acid, abundant in HFD, fully recapitulates the effect of HFD on the self-renewal of PML::RARA HPCs through activation of peroxisome proliferator-activated receptor delta, a central regulator of fatty acid metabolism. Our findings inform dietary/pharmacologic interventions to counteract obesity-associated cancers and suggest that nongenetic factors play a key role.

Prevention Relevance:

Our work informs interventions aimed at counteracting the cancer-promoting effect of obesity. On the basis of our study, individuals with a history of chronic obesity may still significantly reduce their risk by switching to a healthier lifestyle, a concept supported by evidence in solid tumors but not yet in hematologic malignancies.

See related Spotlight, p. 47
TABLE 6 from Risk Prediction of Metachronous Colorectal Cancer from Molecular Features of Adenomas: A Nested Case–Control Study
Authors: Jodal Henriette C. , Akwiwu Eddymurphy U. , Lemmens Margriet , Delis-van Diemen Pien M. , Klotz Dagmar , Leon Leticia G. , Lakbir Soufyan , de Wit Meike , Fijneman Remond J.A. , van Leerdam Monique E. , Dekker Evelien , Spaander Manon C.W. , Meijer Gerrit A. , Løberg Magnus , Coupé Veerle M.H. , Kalager Mette , Carvalho Beatriz
Published: November 2023

Comparisons of subgroups to explore the interaction between morphologic and molecular risk definitions in the association with me-CRC risk
FIGURE 1 from Risk Prediction of Metachronous Colorectal Cancer from Molecular Features of Adenomas: A Nested Case–Control Study
Authors: Jodal Henriette C. , Akwiwu Eddymurphy U. , Lemmens Margriet , Delis-van Diemen Pien M. , Klotz Dagmar , Leon Leticia G. , Lakbir Soufyan , de Wit Meike , Fijneman Remond J.A. , van Leerdam Monique E. , Dekker Evelien , Spaander Manon C.W. , Meijer Gerrit A. , Løberg Magnus , Coupé Veerle M.H. , Kalager Mette , Carvalho Beatriz
Published: November 2023

Flowchart of the selection and analysis of the study cases. A, Selection of samples with complete molecular and morphologic information available. B, Selection of samples used in the case–control comparison (incidence density matching analysis). FFPE, formalin-fixed paraffin-embedded; AA, advanced adenoma; me-CRC, metachronous colorectal cancer.
Case Report of Anti-Thrombogenicity
Authors: Boedecker-Lips Simone C. , Batzke Katharina , Klimpke Pascal , Holtz Stefan , Kraus Daniel , Weinmann-Menke Julia
Published: November 2023

Background: The Toray Filtryzer™-NF is a new polymethyl methacrylate filter with improved hemocompatibility and reduced impact on platelet counts. Objectives: This suggests that, if necessary, a reduction in anticoagulation may be possible when dialysis is performed with the Toray Filtryzer™-NF. Methods: In the following, we dialyzed 5 hemodialysis patients who had a contraindication to full anticoagulation postoperatively or after renal biopsy with the Filtryzer™-NF. Results: A significant reduction in heparin administration was achieved, and in 1 patient, heparin substitution was completely omitted. Despite the significantly reduced heparin doses, no thrombosis of the system occurred during the hemodialysis. Conclusion: In conclusion, hemodialysis using the Toray Filtryzer™-NF is an effective alternative for patients at significantly increased risk of bleeding.
Epithelial Carcinomas Arising within Phyllodes Tumours of the Breast: A Review of Their Pathological Characteristics
Authors: Cook William , Lee Cheok Soon , Tan Puay Hoon
Published: November 2023

Epithelial proliferation is a common feature of phyllodes tumours (PTs), but epithelial malignancy is rare. This review seeks to further our understanding of epithelial malignancy within PTs by analysing their histopathological characteristics in previously reported cases and providing an overview of studies on their pathological features. PubMed and DeepDyve were searched for case reports, case series, and literature reviews of in situ and invasive carcinoma within PTs. Only cases where the carcinoma was within the PT were included. Cases of synchronous carcinoma in the ipsilateral or contralateral breast were excluded. Ninety-eight cases of in situ or invasive carcinoma within a PT were identified. Across the grades of PTs, there was a similar proportion of invasive carcinomas compared to in situ lesions. Malignant PT correlates with a higher likelihood of epithelial malignancy, and molecular studies support a possible causal pathophysiological relationship. This higher likelihood may suggest interactions between malignant stroma and the transforming epithelium that could potentially play a significant role in the phenomenon, which remains to be elucidated. Encasement within a PT likely improves the prognosis of breast carcinoma due to earlier detection. The presence of carcinoma within a malignant PT has uncertain prognostic implications. Thorough sampling of all PTs is recommended for appropriate prognostication and management.
LAG3 and TIGIT Expression on Tumor-Infiltrating Lymphocytes in Cutaneous Melanoma
Authors: Naimy Soraya , Bzorek Michael , Eriksen Jens Ole , Løvendorf Marianne Bengtson , Litman Thomas , Dyring-Andersen Beatrice , Gjerdrum Lise Mette Rahbek
Published: November 2023

Background: Melanoma is widely recognized to be an immunogenic tumor that often contains tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment. During cancer progression, expression of ligands that bind immune checkpoint (IC) proteins, such as PD-1, expressed on the surface of TILs, hinder them from exerting their antitumor functions. TILs consist of a heterogenous group of immune cells and their presence is associated with an improved overall survival in melanoma patients. Introduction of IC inhibitors has revolutionized management and prognosis of advanced melanoma. Unfortunately, the response rates have continued to be limited, resulting in growing interest in characterizing novel IC proteins, and developing combination therapy that includes inhibitors against multiple IC proteins. Methods: In a regional cohort of 166 patients diagnosed with cutaneous superficial spreading melanoma with different degree of TILs, we investigated the tumor immune-associated gene expression profile using NanoString Technology. We used multiplex immunofluorescence (mIF) staining in a subset of tumors (N = 7), combining IC proteins T-cell immunoglobulin and ITIM domain (TIGIT) and LAG3 with a melanoma cell marker (SOX10) and immune cell markers (CD8 [cytotoxic T cells], CD4 [T helper cells], FOXP3 [regulatory T cells/Tregs], PAX5 [B cells], and CD56 [NK/NKT cells]) and IC protein PD-1. Results: We found upregulation of 91 differentially expressed genes, including IC proteins, LAG3 and TIGIT in melanomas with brisk TILs compared to tumors where TILs were absent. mIF staining revealed LAG3 and TIGIT expression in the majority of CD8+ T cells. Only few Tregs and CD4+ T cells expressed LAG3, whereas majority of them expressed TIGIT. LAG3 and TIGIT were expressed in a small fraction of the NK/NKT cells and lacked in the B cells. The majority of PD-1+ cells co-localized with LAG3 and TIGIT. Conclusion: We report a variable expression of LAG3 and TIGIT on TILs subtypes and a coeval occurrence with PD-1. This knowledge places LAG3 and TIGIT in spatial and cellular context in melanoma. The data suggest that targeting multiple IC proteins might help overcome the current challenges with IC therapies.
Nonfamilial Bilateral Synchronous Renal Cell Carcinoma with Discordant Histology with Eventual Complete Response to Dual Immunotherapy
Authors: Robertson Ian J. , Grigsby Sierrah M. , Mattingly John C. , Park Dean K.
Published: November 2023

Bilateral synchronous renal cell carcinoma (RCC) is rare, especially in sporadic rather than familial cases. While immunotherapy has improved prognosis, RCC remains a diagnosis with significant morbidity and mortality, particularly pronounced in patients with sarcomatoid RCC (sRCC). We describe a case of a patient with bilateral, synchronous, nonfamilial RCC, with and without sarcomatoid features and differing genetic markers, who demonstrated a pathologic response after neoadjuvant nivolumab and ipilimumab. The patient then had radical left nephrectomy and partial right nephrectomy followed by adjuvant nivolumab and cabozantinib, after which the patient had no evidence of disease. Our patient’s illustrative case shows the potential therapeutic value of immunotherapy even in sRCC, the disease’s most aggressive clinical subtype.
Successful Liberation from Acute Kidney Replacement Therapy in Critically Ill Patients: A Prospective Cohort Study
Authors: Suarez Maria Irma Rodriguez , Ohara Cristine Naomi , Kitawara Koody Andre Hassemi , Zamoner Welder , Balbi Andre Luis , Ponce Daniela
Published: November 2023

Introduction: Recovery of kidney function to liberate patients from acute kidney replacement therapy (AKRT) is recognized as a vital patient-centered outcome. The lack of specific guidelines providing specific recommendations on therapy interruption is an important obstacle. We aimed to determine the prevalence of successful discontinuation of AKRT and its predictive factors after the elaboration of clinical protocol with these recommendations. Methodology: A prospective cohort study was performed with 156 patients at a public Brazilian university hospital between July 2020 and July 2021. Results: Success and hospital discharge were achieved for most patients (84.6% and 89%, respectively). Multivariable logistic regression analysis showed that C-reactive protein (CRP), urine output, and creatinine clearance at the time of interruption were variables associated with discontinuation success (OR: 0.943, CI: 0.905–0.983, p = 0.006; OR: 1.078, CI: 1.008–1.173, p = 0.009 and OR: 1.091, CI: 1.012–1.213, p = 0.004; respectively). The areas under the curve for CRP, urine output, and creatinine clearance at the time of interruption were 0.78, 0.62, and 0.82, respectively. Both CRP and creatinine clearance were good predictors of successful liberation of AKRT. The optimal cutoff value of them had sensitivity and specificity of 0.88 and 0.87, 0.91 and 0.90, respectively. The use of noradrenalin at the time of interruption (OR: 0.143, CI: 0.047–0.441, p = 0.001) and successful discontinuation (OR: 3.745, CI: 1.047–13.393, p = 0.042) were identified as variables associated with hospital discharge. Conclusion: Our results show the factors related to success in discontinuing AKRT are the CRP, creatinine clearances, and urinary output at the time of AKRT interruption and it was associated with lower mortality.
Relationship between Mediterranean Diet and Phase Angle in a Sample of Patients with Obesity and Metabolic Syndrome
Authors: de Luis Daniel , Primo David , Izaola Olatz , Lopez Gomez Juan José
Published: November 2023

Introduction: The potential influence of a Mediterranean diet (MD) on PhA values has been little researched. The aim of this study was to investigate the association between adherence of a MD and PhA on adult sample population with obesity and metabolic syndrome. Methods: We conducted a cross-sectional study in 331 patients with obesity and metabolic syndrome. Anthropometrics’ data (weight, height, body mass index, and waist circumference), bioelectrical bioimpedance (BIA) parameters (resistance reactance, PhA, fat mass [FM], fat-free mass [FFM], skeletal muscle mass [SMM]), and biochemical parameters were recorded. Dietary intakes with a 3-day written food records and MD adherence with a validated 14-item questionnaire were evaluated. Patients were divided into two groups by median value of PhA. Results: Percentage of patients with high MD adherence (score >7) in high PhA group was 77.2% and in low PhA group was 41.4% (odds ratio 1.91, 95% CI = 1.27–3.54; p = 0.01). Total fat intake (saturated, monounsaturated, and polyunsaturated fats), protein intake, and cholesterol intake were higher in high PhA group than low PhA group. Total score of MD was higher in high PhA than low PhA group (3.5 ± 1.1 points; p = 0.04). FFM (3.3 ± 0.9 kg; p = 0.01), FFM index (3.9 ± 1.1 kg/m2; p = 0.01), SMM (4.6 ± 1.2 kg; p = 0.01) and SMM index (3.3 ± 0.7 kg/m2; p = 0.03) were higher in subjects of high adherence of MD group than subjects of low adherence. FM (−3.2 ± 1.1 kg; p = 0.03) was lower in subjects with good adherence to MD. MD score (Beta 1.71, CI 95% 1.06–2.16), FFM (Beta 3.99, CI 95% 1.87–7.16), and SMM (Beta 4.21, CI 95% 1.76–8.19) remained in the multivariate model. Conclusion: We concluded that a high adherence to a MD in subjects with obesity and metabolic syndrome is associated with values of PhA.
Comparative Cytogenetic Analysis of Diploid and Triploid Pacific Abalone, Haliotis discus hannai
Authors: Zhang Jianpeng , Wang Yi , Lu Ying , You Weiwei , Luo Xuan , Ke Caihuan
Published: November 2023

Introduction: The Pacific abalone, Haliotis discus hannai, is one of the most commercially important marine shellfish in China. Cell engineering breeding is an important tool in abalone genetic breeding, and the triploids obtained through this method have high commercial value. However, current research mainly focuses on establishing induction methods and evaluating the growth traits of triploids, while there is a lack of basic research on triploid cytogenetics. Method: In this study, Cytogenetic analysis of triploid Haliotis discus hannai larvae (produced by chemical treatment) and diploid larvae was performed. Result: The results showed that triploid H. discus hannai had a chromosome number of 3n = 54, consisting of 30 metacentric (m) and 24 submetacentric (sm) chromosomes, while the diploids had a chromosome number of 2n = 36, consisting of 20 metacentric (m) and 16 submetacentric (sm) chromosomes. Notably, both triploids and diploids displayed variation in the number of NORs and/or their diameter. The average number of NORs in triploid was significantly higher than that in diploids (p < 0.05), but the average diameter of NORs of triploid was no significant different from that of diploid (p > 0.05). Additionally, 5S rDNA localization to 3 submetacentric chromosomes was observed in triploids, compared to 2 submetacentric chromosomes in diploids. The number of 18S rDNA sites displayed positional conservancy and quantitative variability in both diploids and triploids. Specifically, 18S rDNA was found at the end of the chromosome in both groups, with triploids exhibiting a significantly higher number of loci than diploids (p < 0.01). Conclusion: This study provides valuable insights into the cytogenetic characteristics of triploid H. discus hannai, which could facilitate further research on the stability of the chromosome set in this species.
Apenas maioria qualificada do Supremo Tribunal Federal deveria deter poder de declarar inconstitucionalidade de emenda constitucional
Authors: Garcia Fernando Couto
Published: November 2023

O artigo procura responder à seguinte questão: qual o quorum adequado para que o Supremo Tribunal Federal declare a inconstitucionalidade de uma emenda constitucional aprovada pelo poder constituinte reformador mediante maioria qualificada? Por meio da comparação com outras hipóteses de maioria qualificada previstas na Constituição e reflexão sobre os fundamentos da regra da maioria, baseadas em teoria desenvolvida por Jeremy Waldron, chega-se à conclusão de que esta declaração só deveria ser possível mediante maioria qualificada dos membros do tribunal.
Digital democracy e inclusão digital indígena como fortalecimento do pluralismo jurídico
Authors: Oliveira Denizom Moreira de
Published: November 2023

O artigo realiza uma análise sobre os impactos da exclusão digital dos povos indígenas na sua efetiva participação política, sobretudo no contexto de fortalecimento democrática e pluralista na América Latina. O estudo é divido em duas partes: (i) a primeira, analisando os gaps digitais existentes entre indígenas e não indígenas, obstaculizando o direito à inclusão digital e os direitos específicos dos povos indígenas, assemelhando-se ao seu direito ao território e a autodeterminação e; (ii) a segunda, avaliando, a partir de casos práticos, a inclusão digital dos povos indígenas como fortalecimento de direitos democráticos, especialmente no contexto da digital democracy e do pluralismo jurídico.
O direito natural entre a superstição e o entusiasmo: o “conteúdo mínimo de direito natural” em H.L.A. Hart e a influência do ceticismo moral de David Hume
Authors: Petiz Martin Magnus
Published: November 2023

David Hume nem sempre é lembrado como um filósofo importante para o juspositivismo. Hume apresentou uma noção convencionalista da justiça como uma alternativa ao “entusiasmo” dos teóricos protestantes de Direito Natural. Para eles, o Direito seria legítimo apenas se respeitasse direitos individuais descobertos pela razão. Por isso, Hume formulou uma teoria descritiva da justiça, a qual se relaciona com a sua teoria política, sua ciência política e, em abstrato, com a sua filosofia. A hipótese desse artigo é a de que H.L.A. Hart aderiu a esses pressupostos ao formular a sua concepção de “conteúdo mínimo de Direito Natural”, implicitamente, o que deixou ambíguo o sentido de passagens importantes do seu O conceito de direito. O objetivo do trabalho é expor esses pressupostos. Algumas interpretações veem nas afirmações de Hart sobre os truísmos uma admissão da conexão entre o Direito e a moral. No entanto, com a influência de Hume evidenciada, podemos compreender que os truísmos de Direito Natural não são prescrições, mas generalizações ou máximas empíricas retiradas de uma espécie de História Natural da espécie humana. Após apresentar aspectos centrais da filosofia de Hume, serão expostas similaridades e conexões com a teoria de Hart. A confirmação da hipótese tem importantes consequências para se compreender o que Hart entendia como “Direito Natural”. Embora o conteúdo mínimo não implique o total abandono da tese da separação, a iluminação dos pressupostos Humeanos mostra a fragilidade de uma Teoria do Direito descritivista e amoral, como Hume e Hart pretendiam.
Decreases in Rhinology Care Utilization by People with Cystic Fibrosis on Highly Effective Modulator Therapy
Authors: Han Ethan J. , Beswick Daniel M. , Eshaghian Patricia H. , Turner Grant A. , Lee Jivianne T. , Li Douglas A. , Wang Marilene B. , Taylor-Cousar Jennifer L. , Suh Jeffrey D.
Published: November 2023

Background:

Many people with cystic fibrosis (PwCF) have chronic rhinosinusitis (CRS). CRS requires additional management beyond that of pulmonary disease and leads to increased utilization of healthcare resources. Elexacaftor/tezacaftor/ivacaftor (ETI) is a highly effective modulator therapy that has been shown to improve CRS in PwCF. However, the impact of ETI on rhinologic healthcare utilization is understudied.

Objective:

To compare rates of rhinologic healthcare utilization and procedures among PwCF prior to and after initiating ETI therapy.

Methods:

A single-center, cohort study investigating adult PwCF was performed in January 2023. Demographics, clinical characteristics, and data related to CF treatment were retrospectively abstracted. Characteristics of the cohort were compared over 2 periods: the 12-months prior to ETI initiation and the 12-months after ETI initiation. Post-ETI data were linearly extrapolated if a subject had not yet completed the full 12 months of ETI. Paired t-testing, Wilcoxon signed rank testing, and regression analysis were performed.

Results:

Of 126 PwCF, 98 (77.8%) were on ETI therapy and 35 (27.7%) were both on ETI and concurrently followed by the rhinology service (ETI-ENT). Rhinology clinic visits ( P = .007) and frequency of obtaining nasal cultures ( P = .046) decreased for the ETI-ENT cohort after initiating ETI treatment. There were no significant changes in the number of endoscopic sinus surgeries ( P = .452) performed. Beyond ETI use, regression analysis did not identify any factors associated with changes in utilization.

Conclusion:

Aspects of rhinology healthcare utilization by PwCF decreased after initiation of ETI therapy. Additional studies are needed to determine rhinologic healthcare requirements for PwCF who remain on ETI for the long-term and to evaluate larger cohorts of PwCF on ETI.