bluuebunny/crossref_metadata_2025_split huggingface dataset:
CRISPR knockout genome-wide screens identify the HELQ-RAD52 axis in regulating the repair of cisplatin-induced single-stranded DNA gaps
Authors: Pale Lindsey M , Khatib Jude B , Nusawardhana Alexandra , Straka Joshua , Nicolae Claudia M , Moldovan George-Lucian 
Published: November 2024

Abstract
Treatment with genotoxic agents, such as platinum compounds, is still the mainstay therapeutical approach for the majority of cancers. Our understanding of the mechanisms of action of these drugs is, however, imperfect and continuously evolving. Recent advances highlighted single-stranded DNA (ssDNA) gap accumulation as a potential determinant underlying cisplatin chemosensitivity, at least in some genetic backgrounds, such as BRCA mutations. Cisplatin-induced ssDNA gaps form upon restart of DNA synthesis downstream of cisplatin-induced lesions through repriming catalyzed by the PRIMPOL enzyme. Here, we show that PRIMPOL overexpression in otherwise wild-type cells results in accumulation of cisplatin-induced ssDNA gaps without sensitizing cells to cisplatin, suggesting that ssDNA gap accumulation does not confer cisplatin sensitivity in BRCA-proficient cells. To understand how ssDNA gaps may cause cellular sensitivity, we employed CRISPR-mediated genome-wide genetic screening to identify factors which enable the cytotoxicity of cisplatin-induced ssDNA gaps. We found that the helicase HELQ specifically suppresses cisplatin sensitivity in PRIMPOL-overexpressing cells, and this is associated with reduced ssDNA accumulation. We moreover identify RAD52 as a mediator of this pathway. RAD52 promotes ssDNA gap accumulation through a BRCA-mediated mechanism. Our work identified the HELQ-RAD52-BRCA axis as a regulator of ssDNA gap processing and cisplatin sensitization.
Monocyte/macrophage pyroptosis and C5b-9-induced cyst enlargement in Pkd1−/− mice
Authors: Yang Yang , Kong Deyang , Chen Meihan , Lv Jiayi , Zhou Jie , Xue Cheng , Song Shuwei , Song Minghui , Ma Lu , Mao Zhiguo , Mei Changlin 
Published: November 2024

ABSTRACT

Background and hypothesis
The levels of C5b-9, terminal products of complement activation, were significantly elevated in autosomal dominant polycystic kidney disease (ADPKD). However, the precise mechanisms by which C5b-9 facilitates cyst growth remain incompletely elucidated.

Methods
Three groups of chronic-onset Pkd1−/− mice were established: one group received intravenous injections of 0.5 mg/kg C5b-9, another was administered 1.0 mg/kg monoclonal anti-C9 antibodies, and a control group received 1 mg/kg IgG isotype control. All treatments were administered biweekly for two months (postnatal day 180–240). Renal macrophages from distinct subsets were sorted using fluorescence-activated cell sorting. To deplete macrophages, liposome clodronate was injected intraperitoneally. Sublethal irradiation followed by bone marrow reconstruction was performed in Pkd1−/− mice to evaluate the role of bone marrow-derived macrophages (BMDMs) in ADPKD progression.

Results
(i) In vitro, sublytic C5b-9 did not affect the viability of renal tubular epithelial cells, but significantly induced M1-like polarization and pyroptosis of BMDMs. (ii) In vivo, C5b-9 notably triggered pyroptosis of Ly6C+ monocytes and a reduction in circulating monocyte numbers as cysts enlarged. (iii) Residual Ly6C+ monocytes infiltrated renal tissues and differentiated into Ly6C+ macrophages, which exhibited a greater susceptibility to pyroptosis compared to Ly6C− macrophages. (iv) Although limited evidence has recently suggested that Ly6C− monocytes may also be affected by C5b-9, upregulation of CCR2 in Ly6C− macrophages was observed in C5b-9-treated Pkd1−/− mice, implying that Ly6C− monocytes could represent a significant source of M2 macrophages.

Conclusions
C5b-9 infusion promoted renal tubular epithelial cell proliferation by inducing pyroptosis of Ly6C+ monocytes/macrophages, contributing to progressive cyst enlargement in chronic-onset PKD mice.
The prognostic impact of CDKN2A/B hemizygous deletions in IDH-mutant glioma
Authors: Ippen Franziska M , Hielscher Thomas , Friedel Dennis , Göbel Kirsten , Reuss David , Herold-Mende Christel , Krieg Sandro , Deimling Andreas v , Wick Wolfgang , Sahm Felix , Suwala Abigail K 
Published: November 2024

Abstract

Background
Homozygous deletions of CDKN2A/B are known to predict poor prognosis in gliomas, but the impact of hemizygous deletions is less clear. This study aimed to evaluate the prognostic significance of hemizygous CDKN2A/B deletions in IDH-mutant low-grade astrocytomas and oligodendrogliomas.

Methods
Tissue samples diagnosed as astrocytoma, IDH-mutant and oligodendroglioma, IDH-mutant, 1p/19q co-deleted CNS WHO grade 2 and 3 were collected from the archives of the Institute of Neuropathology in Heidelberg. DNA methylation analysis was performed on formalin-fixed paraffin-embedded samples. Evaluation of the CDKN2A/B locus was performed by visual inspection of copy-number plots derived from methylation-array data for each case. Hemizygous and homozygous losses were assessed in relation to whole chromosomal or larger segmental losses and gains in the chromosomal profile. Survival probabilities were assessed using the Kaplan–Meier method.

Results
A total of 334 low-grade glioma cases were identified, including 173 astrocytomas and 161 oligodendrogliomas. Hemizygous deletions in CDKN2A/B (37/173 in astrocytomas, 15/161 in oligodendrogliomas) did not confer significantly worse survival outcomes compared to CDKN2A/B wild-type cases in neither low-grade astrocytoma (log-rank P = .2556; HR 2.29, 95% CI [0.76; 6.40], P = .135) nor oligodendroglioma (log-rank P = .2760; HR 0.17; 95% CI [0.01; 5.05]; P = .305), regardless of CNS WHO grade, which was further demonstrated on a subgroup of astrocytoma, IDH mutant CNS WHO 4 cases (log-rank P = .1680; HR 4.55, 95% CI [0.88; 24.51], P = .0689).

Conclusions
Hemizygous CDKN2A/B deletions do not significantly worsen OS or progression-free survival in IDH-mutant astrocytomas and oligodendrogliomas, CNS WHO grades 2 and 3.
Health Benefits of Olive Leaf: The Focus on Efficacy of Antiglycation Mechanisms
Authors: Demirer Büşra , Samur Gülhan 
Published: November 2024

Abstract
Olive leaves have been a therapeutic herbal agent for diseases for centuries. Olive leaves contain many health-beneficial nutrients and bioactive components. There is much evidence for the positive effects of the phenolic compounds they contain on health. The main active phenolic component in olive leaves is oleuropein, which can constitute 6%–9% of the leaf's dry matter and has been intensively studied for its promising results/effects on human health. In addition, olive leaf provides health benefits through bioactive components, such as secoiridoids, flavonoids, triterpenes, and lignans. The anti-inflammatory, antioxidant, anticancer, antidiabetic, and antihypertensive properties of bioactive components, especially oleuropein, are well known. In addition, various health benefits, such as neuroprotective effects and microbiota modulation, are also mentioned. In recent years, in vitro studies have shown that olive leaves and bioactive components from olive leaves may have antiglycation effects. Currently, it is thought that the components found in olive leaves have a direct or indirect antiglycation effect. It is thought that, their direct effects include reducing the interaction between sugars and amino acids, nucleic acids, and lipids and sequestering reactive dicarbonyl species, and their indirect effects include preventing the formation of advanced glycation end-products (AGEs) by reducing inflammation and oxidative stress. However, in vivo and clinical studies are needed to prove these mechanisms and understand how their metabolism works in the human body. This review examines the beneficial health effects of olive leaves and their potential antiglycation role.
Effect of Fatty Acids on Glucose Metabolism and Type 2 Diabetes
Authors: Sivri Dilek , Akdevelioğlu Yasemin 
Published: November 2024

Abstract
Type 2 diabetes is an inflammatory, non-infectious disease characterized by dysfunctional pancreatic β-cells and insulin resistance. Although lifestyle, genetic, and environmental factors are associated with a high risk of type 2 diabetes, nutrition remains one of the most significant factors. Specific types and increased amounts of dietary fatty acids are associated with type 2 diabetes and its complications. Dietary recommendations for the prevention of type 2 diabetes advocate for a diet that is characterized by reduced saturated fatty acids and trans fatty acids alongside an increased consumption of monounsaturated fatty acids, polyunsaturated fatty acids, and omega-3 fatty acids. Although following the recommendations for dietary fatty acid intake is important for reducing type 2 diabetes and its related complications, the underlying mechanisms remain unclear. This review will provide an update on the mechanisms of action of fatty acids on glucose metabolism and type 2 diabetes, as well as dietary recommendations for the prevention of type 2 diabetes.
Effect of the Mediterranean Diet Supplemented With Olive Oil Versus the Low-Fat Diet on Serum Inflammatory and Endothelial Indexes Among Adults: A Systematic Review and Meta-analysis of Clinical Controlled Trials
Authors: Pourrajab Behnaz , Fotros Danial , Asghari Parastoo , Shidfar Farzad 
Published: November 2024

Abstract

Context
Inflammation and endothelial dysfunction are important risk factors for chronic diseases, including cardiovascular diseases and related mortality.

Objective
This systematic review and meta-analysis aimed to assess the effects of 2 popular dietary patterns—a Mediterranean (MED) diet supplemented with olive oil and a low-fat diet (LFD)—on factors related to inflammation and endothelial function in adults.

Data Sources and Data Extraction
The following online databases were searched for related studies published until August 7, 2024: PubMed/Medline, Scopus, Clarivate Analytics Web of Science, Cochrane Central Register of Controlled Trials, and Google Scholar. Two independent researchers selected the studies based on the eligibility criteria.

Data Analysis
The effect sizes were expressed as Hedges' g with 95% CIs. A total of 16 eligible trials with 20 effect sizes were included in the analyses. This meta-analysis revealed that the MED diet supplemented with olive oil significantly improved all of the indicators of the study compared with the LFD, except in the case of E-selectin, in which a low and nonsignificant decrease was reported.

Conclusion
Available evidence suggests that a MED diet supplemented with olive oil compared with the LFD significantly improves inflammation and serum endothelial function in adults.

Systematic Review Registration
PROSPERO registration no. CRD42023485718.
Unravelling the Role of Chitin and Chitosan in Prebiotic Activity and Correlation With Cancer: A Narrative Review
Authors: Ferri Irene , Canala Benedetta , Rossi Luciana 
Published: November 2024

Abstract
This review describes the state of the art regarding the prebiotic role of chitin and the interactions of chitin and chitosan with cancer cells. Chitin is the second most abundant polysaccharide in nature and a constitutive component of crustacean shells and the exoskeleton of insects. Chitosan is the deacetylated form of chitin, which is obtained by chemical processing or the enzymatic activity of deacetylases found in microorganisms and insects. Edible insects have recently been introduced in Western countries, thus raising concerns regarding food safety and due to their chitin content and the release of chitosan during the digestive process. The roles of insect chitin and chitosan in the gastrointestinal tract, microbiome modulation, and cancer have been widely investigated. Several in vitro and in vivo studies have shown the possible microbiota modulation of chitin and its relevant communication with the immune system, thus confirming its prebiotic activity. No evidence has been provided on the cancerogenic activity of chitin; however, studies have suggested that chitin has a cytotoxic effect on cancer cell lines. Chitosan has been confirmed to exhibit apoptotic and cytotoxic activities on cancer cells in several in vitro studies on cancer cell lines and in vivo models. In conclusion, the literature does not show a direct connection between the presence of chitin or chitosan and the onset of cancer. However, cytotoxic and apoptotic activities in relation to cancerous lines have been demonstrated.
Petrology of Tourmaline-Bearing Blueschist from SW Tianshan, China, and Its Implication in B-Rich Fluid Migration in Subduction Zone
Authors: Shen Tingting , Hu Han , Zhang Lifei , Xu Jie Dodo , Tian Zuolin , Bader Thomas , Ma Jinlong , Zhang Jianxin , Peng Weigang , Yang Jingsui 
Published: November 2024

Abstract
Boron geochemistry can track fluid–rock interaction during subduction zone metamorphism. Rare tourmaline-bearing blueschists, which are associated with ultrahigh-pressure (UHP) serpentinites are first recognized in SW Tianshan, China. Detailed petrology, whole-rock and mineral chemistry, B isotope analysis, and modeling characterized two consecutive stages of tourmaline crystallization (Tur-I, Tur-II). Tourmaline included in, or intergrown with, garnet and the cores of tourmaline in rock matrixes and veins are Tur-I, which grew during prograde metamorphism at 430°C to 460°C/470°C, ~1.9–2.1 GPa. The rims of tourmaline in rock matrixes and veins are Tur-II, which formed during initial exhumation at 460°C to 490°C, ~2.1–1.7 GPa. Variable δ11B values of tourmaline (+8‰, Tur-I to −2‰, Tur-II) point to a 11B-rich signature of the fluid infiltrating at Stage I. With progressing metamorphism, δ11B decreased in the fluid. The high-δ11B Tur-I (up to +8‰) could not have crystallized from fluid released from the high-pressure metapelites (−12‰ to −7‰) and metabasites (−15‰ to −5‰) surrounding the tourmaline host rocks given the lower δ11B values. Modeling of B isotope fractionation yields the δ11B values of −9‰ to −5‰, −11‰ to −1‰, and +8‰ to +17‰ for the fluids equilibrium with the restitic metapelites, metabasites, and serpentinites, respectively. The tourmaline and whole-rock B isotope data, along with the tourmaline compositions, point to the associated serpentinites as source of the fluid that infiltrated the metamorphic rocks. This fluid was released by the partial dehydration of serpentinites through the reaction antigorite + brucite = olivine + water at forearc depth. We propose that metabasites in subduction zones can acquire 11B-rich signatures through interaction with serpentinite-derived fluids, leading to the formation of robust tourmaline minerals at shallow levels. As a new reservoir of heavy boron, these metabasites can then transport this signature to greater depths.
Carbon and nitrogen signaling regulate FLOWERING LOCUS C and impact flowering time in Arabidopsis
Authors: Gramma Vladislav , Olas Justyna Jadwiga , Zacharaki Vasiliki , Ponnu Jathish , Musialak-Lange Magdalena , Wahl Vanessa 
Published: November 2024

Abstract
The timing of flowering in plants is modulated by both carbon (C) and nitrogen (N) signaling pathways. In a previous study, we established a pivotal role of the sucrose-signaling trehalose 6-phosphate pathway in regulating flowering under N-limited short-day conditions. In this work, we show that both wild-type Arabidopsis (Arabidopsis thaliana) plants grown under N-limited conditions and knock-down plants of TREHALOSE PHOSPHATE SYNTHASE 1 induce FLOWERING LOCUS C (FLC) expression, a well-known floral repressor associated with vernalization. When exposed to an extended period of cold, a flc mutant fails to respond to N availability and flowers at the same time under N-limited and full-nutrition conditions. Our data suggest that SUCROSE NON-FERMENTING 1 RELATED KINASE 1-dependent trehalose 6-phosphate-mediated C signaling and a mechanism downstream of N signaling (likely involving NIN-LIKE PROTEIN 7) impact the expression of FLC. Collectively, our data underscore the existence of a multi-factor regulatory system in which the C and N signaling pathways jointly govern the regulation of flowering in plants.
Partnership between the Swedish police and civil society organizations. Encouraging and hindering factors for a successful collaboration
Authors: Jonsson Cecilia 
Published: November 2024

Abstract
The notion that the police need to work in interorganizational partnerships has been well-established for decades, although the task has proved difficult. Based on interviews with representatives from strategically selected CSOs, this study examines encouraging and hindering factors for collaboration with the police. It also shows that the statements of the three CSOs echo previous research where the police is involved. The study concludes that firstly, the police must recognize the CSOs as trustworthy and consider their activities to be of police interest. Secondly, the CSOs must manage to penetrate the police organization’s physical and cultural boundaries in order to offer their services. Thirdly, a division of labour must be established where the benefits of collaboration are evident for both parties. Fourthly, collaboration must be organizationally institutionalized. It is worth noting that not all CSOs strive for closer collaboration; some prefer to keep a distance.
Strong Absorptions of Thermal Neutrons Caused by Virtual States
Authors: Yamaguchi Yukito , Okada M , Terao T , Furusho S , Okamoto T , Yagi Y , Fumimoto T , Maeda T , Nakamoto R , Ito M 
Published: November 2024

Abstract
Cross sections of compound nucleus (CN) formation by S-wave neutron scattering, the study of which was begun by Feshbach et al. in a pioneering work, are reanalyzed by the optical model plus the Jost function method (JFM), which is a modern theory for handling bound and unbound continuum states in a unified manner. We have calculated the CN cross section for thermal neutron scattering ($E_n=25.3$ meV) by about 300 stable targets. The enhancements in the CN cross section in specific mass number regions, $A\sim 10, 50$, and 160, which are well known results in the previous optical model analyses, are reproduced by the present calculation. The JFM calculation is applied to investigate the origin of the enhanced CN cross section, and the poles in the scattering matrices (S-matrices) are systematically explored in the complex momentum plane. In JFM, the S-matrix poles representing the virtual states, which are different from the usual resonances described by the Breit–Wigner formula, appear around the origin (zero energy) in the momentum plane in the mass region with the enhanced CN cross section. The present analysis of the S-matrix means that the virtual state strongly enhances the CN cross section. We also discuss the present results in connection with giant resonances and compound nuclear resonances, which were regarded in previous studies as established theories to understand the enhanced absorption of the thermal neutron.
“Superstitious” Investors
Authors: Guo Hongye , Wachter Jessica A 
Published: November 2024

Abstract
We reconsider the excess volatility puzzle through the lens of a model in which agents believe they can predict dividend growth when in fact they cannot. Besides excess volatility in the time series, the model explains the value premium, and the explanatory power of the value factor. In support of the model, we show that analysts’ earnings forecasts align with market valuation and that analysts are far more optimistic about growth stocks than they are about value stocks. Using both survey and price data, we show that the same mechanism can explain the excess returns earned by investing in high-interest rate currencies. (JEL G12, G15, G41)
Disseminated Knowledge: The Advancement of Finnish Occupational Medicine and Work Psychology in a Transnational Context, c. 1945–1952
Authors: Mannevuo Mona 
Published: November 2024

Summary
This article focuses on the advancement of Finnish occupational medicine in the immediate post-war period, situating its development within a transnational context. Its objective is to offer insight into Finnish post-war industrial medicine and particularly developments in mental health care. The empirical methodology addresses a previously unexplored case study: the connections between the Finnish Institute of Occupational Health (FIOH) and Roffey Park Rehabilitation Centre, established in 1943 to address various cases of industrial neurosis. The case study sheds light on the ways in which FIOH adopted reformist ideas from transnational medical communities by aligning them with the needs of Finland’s war reparations industry. The article argues that FIOH’s experts advanced new theories of mental disorder for Finland’s newly modern industrial society, and that these initiatives should be situated within broader transnational endeavours in the mental hygiene movement.
Intracellular Mg2+ concentrations are differentially regulated in the sperm head and mid‐piece in acrosome reaction inducing conditions
Authors: Sánchez‐Cárdenas C. , De la Vega‐Beltrán J. L. , Weber W. D. , Orta G. , Sánchez‐Guevara Y. , Hernández‐Cruz A. , Darszon A. , Visconti P. E. 
Published: November 2024

AbstractThe sperm ability to fertilize involves the regulation of ATP levels. Because inside cells, ATP is complexed with Mg2+ ions, changes in ATP levels result in changes in intracellular Mg2+ concentration ([Mg2+]i), which can be followed using intracellular Mg2+ sensors such as Mag‐520. In this work, we tested conditions known to decrease sperm ATP such as starvation and capacitation. As expected, in these conditions [Mg2+]i increased in all cell compartments. In contrast, when ATP increases, such as adding nutrients to starved sperm, [Mg2+]i significantly decreases in all compartments. On the other hand, when the acrosome reaction was induced, either with progesterone or with ionomycin, [Mg2+]i was differentially regulated in the head and mid‐piece. While Mag‐520 fluorescence increased in the sperm mid‐piece, it decreased in the head. These changes were observed in capacitated as well as in starved sperm but not in sperm incubated in conditions that do not support capacitation. Changes in [Mg2+]i were still observed when the sperm were incubated in high extracellular Mg2+ suggesting that this decrease is not due to Mg2+ efflux. Interestingly, the progesterone and ionomycin effects on [Mg2+]i were abolished on sperm incubated in Ca2+‐free media. Altogether, these results indicate that [Mg2+]i is regulated in sperm during capacitation and acrosomal reaction, and suggest that these measurements can serve to evaluate ATP levels in real time.