bluuebunny/crossref_metadata_2025 huggingface dataset:
Downregulation of Ubiquitin-Specific Protease 15 (USP15) Does Not Provide Therapeutic Benefit in Experimental Mesial Temporal Lobe Epilepsy
Authors: Häussler Ute , Neres João , Vandenplas Catherine , Eykens Caroline , Kadiu Irena , Schramm Carolin , Fleurance Renaud , Stanley Phil , Godard Patrice , de Mot Laurane , van Eyll Jonathan , Knobeloch Klaus-Peter , Haas Carola A. , Dedeurwaerdere Stefanie
Published: October 2023

Structural epilepsies display complex immune activation signatures. However, it is unclear which neuroinflammatory pathways drive pathobiology. Transcriptome studies of brain resections from mesial temporal lobe epilepsy (mTLE) patients revealed a dysregulation of transforming growth factor β, interferon α/β, and nuclear factor erythroid 2-related factor 2 pathways. Since these pathways are regulated by ubiquitin-specific proteases (USP), in particular USP15, we hypothesized that USP15 blockade may provide therapeutic relief in treatment-resistant epilepsies. For validation, transgenic mice which either constitutively or inducibly lack Usp15 gene expression underwent intrahippocampal kainate injections to induce mTLE. We show that the severity of status epilepticus is unaltered in mice constitutively lacking Usp15 compared to wild types. Cell death, reactive gliosis, and changes in the inflammatory transcriptome were pronounced at 4 days after kainate injection. However, these brain inflammation signatures did not differ between genotypes. Likewise, induced deletion of Usp15 in chronic epilepsy did not affect seizure generation, cell death, gliosis, or the transcriptome. Concordantly, siRNA-mediated knockdown of Usp15 in a microglial cell line did not impact inflammatory responses in the form of cytokine release. Our data show that a lack of USP15 is insufficient to modulate the expression of relevant neuroinflammatory pathways in an mTLE mouse model and do not support targeting USP15 as a therapeutic approach for pharmacoresistant epilepsy.
Sevoflurane Exposure Induces Neuronal Cell Ferroptosis Initiated by Increase of Intracellular Hydrogen Peroxide in the Developing Brain via ER Stress ATF3 Activation
Authors: Kang Liheng , Piao Meihua , Liu Nan , Gu Wanping , Feng Chunsheng
Published: October 2023

Neuronal cell death is acknowledged as the primary pathological basis underlying developmental neurotoxicity in response to sevoflurane exposure, but the exact mechanism remains unclear. Ferroptosis is a form of programmed cell death characterized by iron-dependent lipid peroxidation that is driven by hydrogen peroxide (H2O2) and ferrous iron through the Fenton reaction and participates in the pathogenesis of multiple neurological diseases. As stress response factor, activating transcription factor 3 (ATF3) can be activated by the PERK/ATF4 pathway during endoplasmic reticulum (ER) stress, followed by increased intracellular H2O2, which is involved in regulation of apoptosis, autophagy, and ferroptosis. Here, we investigated whether ferroptosis and ATF3 activation were implicated in sevoflurane-induced neuronal cell death in the developing brain. The results showed that sevoflurane exposure induced neuronal death as a result of iron-dependent lipid peroxidation damage secondary to H2O2 accumulation and ferrous iron increase, which was consistent with the criteria for ferroptosis. Furthermore, we observed that increases in iron and H2O2 induced by sevoflurane exposure were associated with the upregulation and nuclear translocation of ATF3 in response to ER stress. Knockdown of ATF3 expression alleviated iron-dependent lipid peroxidation, which prevented sevoflurane-induced neuronal ferroptosis. Mechanistically, ATF3 promoted sevoflurane-induced H2O2 accumulation by activating NOX4 and suppressing catalase, GPX4, and SLC7A11 expression. Additionally, an increase in H2O2 was accompanied by the upregulation of TFR and TF and downregulation of FPN, which linked iron overload to ferroptosis induced by sevoflurane. Taken together, our results demonstrated that ER stress-mediated ATF3 activation contributed to sevoflurane-induced neuronal ferroptosis via H2O2 accumulation and the resultant iron overload.
Psychometric properties of the European Portuguese version of the modified perinatal PTSD questionnaire (PPQ-II)
Authors: Alves Stephanie , Claro Mariana , Beato Ana
Published: October 2023

Childbirth-related posttraumatic stress symptoms (CB-PTSS) are prevalent and have pervasive consequences for the entire family. The development and validation of tools for screening CB-PTSS are deemed necessary to maximize prevention and intervention efforts. This study aims to examine the psychometric properties of the modified perinatal PTSD questionnaire (PPQ-II) in a sample of European Portuguese mothers. Four hundred and fifty-one women, from 1 to 18 months postpartum, participated in an online cross-sectional study that was conducted between February and March 2020. Participants completed the PPQ-II and the Depression Anxiety Stress Scales – 21 (DASS-21). Factor structure was estimated through an Exploratory (EFA; n = 229) and Confirmatory factor analysis (CFA; n = 222). Convergent and known-groups validity and internal consistency of the scale were also computed. The EFA suggested a 2-structure factor (Factor 1 “Arousal”, containing 7 items; and Factor 2 “Avoidance and Intrusion”, containing 4 items), accounting for 48.3% of the total variance of the scale. This factor structure was supported by the CFA, showing an adequate fit to the data. Convergent validity was shown by significant associations between the PPQ-II and DASS-21 subscales. Overall, the scale discriminated between at-risk and low-risk mothers. The McDonald’ omega coefficients attested the high reliability of the PPQ-2 (ranging from 0.78 to 0.89). The PPQ-II is a valid and reliable instrument to routinely screen for CB-PTSS in perinatal health services. It also adds to prior studies demonstrating its cross-cultural validity.
Evaluation of the relationship between Ki67 expression level and neoadjuvant treatment response and prognosis in breast cancer based on the Neo-Bioscore staging system
Authors: Sullu Yurdanur , Tomak Leman , Demirag Guzin , Kuru Bekir , Ozen Necati , Karagoz Filiz
Published: October 2023

Background

Neoadjuvant chemotherapy (NAC) is widely used in the treatment of primary breast cancer. Different staging systems have been developed to evaluate the residual tumor after NAC and classify patients into different prognostic groups. Ki67, a proliferation marker, has been shown to be useful in predicting treatment response and prognosis. We aimed to investigate the prognostic importance Neo-Bioscore stage and pretreatment and posttreatment Ki67 levels in breast cancer patients who received NAC and correlations between Neo-Bioscore stage and pretreatment and posttreatment Ki67 levels.

Methods

A total of 176 invasive breast carcinoma patients who underwent NAC were included in the study. Ki67 levels were evaluated by immunohistochemical methods in Trucut biopsy and surgical excision specimens. Patients were classified into prognostic groups using the Neo-Bioscore staging system.

Results

Patients with high pretreatment Ki67 score were more likely to be in the higher Neo-Bioscore risk group (p < 0.001). Patients with a high posttreatment Ki67 score were more likely to be in the higher Neo-Bioscore prognostic risk group (p < 0.001). Overall survival (OS) and disease-free survival (DFS) were shorter in patients with high posttreatment Ki67 scores and in patients in the higher Neo-Bioscore risk group. We also determined a cutoff 37% for pathological complete response.

Conclusion

Neo-Bioscore staging system is found to be important in predicting survival. The posttreatment Ki67 level is more important than pretreatment Ki67 level in predicting survival.
An overview of the use of the fracture risk assessment tool (FRAX) in osteoporosis
Authors: Schini M. , Johansson H. , Harvey N. C. , Lorentzon M. , Kanis J. A. , McCloskey E. V.
Published: October 2023

FRAX®, a simple-to-use fracture risk calculator, was first released in 2008 and since then has been used increasingly worldwide. By calculating the 10-year probabilities of a major osteoporotic fracture and hip fracture, it assists clinicians when deciding whether further investigation, for example a bone mineral density measurement (BMD), and/or treatment is needed to prevent future fractures. In this review, we explore the literature around osteoporosis and how FRAX has changed its management. We present the characteristics of this tool and describe the use of thresholds (diagnostic and therapeutic). We also present arguments as to why screening with FRAX should be considered. FRAX has several limitations which are described in this review. This review coincides with the release of a version, FRAXplus, which addresses some of these limitations.
On a Non-local Sobolev–Galpern-Type Equation Associated with Random Noise
Authors: Le Dinh Long , Nguyen Duc Phuong , Ragusa Maria Alessandra
Published: October 2023

This paper aims to retrieve the initial value for a non-local fractional Sobolev–Galpern problem. The given data are subject to noise by the discrete random model. We show that the solution to the problem is ill-posed in the sense of Hadamard. In this paper, we applied the Fourier truncation method to construct the regularized solution. We estimate the convergence between the solution and the regularized solution. In addition, the numerical example is also proposed to assess the efficiency of the theory.
Regional evaluation method of ground stress in shale oil reservoirs-taking the Triassic Yanchang formation in northern Shaanxi area as an example
Authors: Hou Bing , Wang Yizhao , Zhang Yu , You Yuan
Published: October 2023

Estimating in-situ stress in shale oil reservoirs is critical for predicting hydraulic fracture height. However, the varied longitudinal lithology and transverse isotropy challenge the regional evaluation of ground stress. A new method based on the Kaiser effect method and the Sn Model was proposed to evaluate regional ground stress from point to point. Kaiser tests obtained the regional tectonic stress coefficients. Combined with the dynamic and static transformation of elastic parameters, the Sn ground stress calculation model suitable for the Northern Shaanxi Area was constructed. According to the calculation results of ground stress in the Chang 7 section of 600 wells in this region, the plane distribution maps of maximum horizontal ground stress (SH) and the difference between SH and Minimum horizontal stress (Sh) were drawn. It was found that the SH in this area was between 20 and 60 MPa, and the So was between 2.6 and 8.8 MPa. Compared with the 3D finite element method simulation results, the forward modeling results coincided well with the inversion results in this research. The causes of the plane distribution of ground stress in the Chang 7 section were explained by regional tectonic stress and paleo topography. It was found that the movement of plate and shell and deposition were critical factors of regional ground stress distribution. The research results provide a reference for further integration of geologic and engineering in evaluating shale oil reservoirs.
Solidification of the Ni-based superalloy CMSX-4 simulated with full complexity in 3-dimensions
Authors: Uddagiri Murali , Shchyglo Oleg , Steinbach Ingo , Tegeler Marvin
Published: October 2023

In this work, we present phase-field (PF) simulations directly coupled to thermodynamic and kinetic databases in three dimensions. The direct coupling allows consideration of the full alloy complexity of the CMSX-4 superalloy over a large range of temperatures. The simulation conditions are chosen for additive manufacturing utilizing Electron Beam Melting (EBM). Transformation of interdendritic liquid into eutectic $$\gamma '$$

γ
′

is considered. The simulation results confirm the unique segregation behavior of all the alloying elements. It is demonstrated that the treatment of the full complexity of alloy composition is superior to all approximations with quasi-binary or -ternary approximation and justifies the significantly increased computational effort. Our results demonstrate that multi-component simulations must become a standard for phase-field applications to real material systems.
Time series adversarial attacks: an investigation of smooth perturbations and defense approaches
Authors: Pialla Gautier , Ismail Fawaz Hassan , Devanne Maxime , Weber Jonathan , Idoumghar Lhassane , Muller Pierre-Alain , Bergmeir Christoph , Schmidt Daniel F. , Webb Geoffrey I. , Forestier Germain
Published: October 2023

Adversarial attacks represent a threat to every deep neural network. They are particularly effective if they can perturb a given model while remaining undetectable. They have been initially introduced for image classifiers, and are well studied for this task. For time series, few attacks have yet been proposed. Most that have are adaptations of attacks previously proposed for image classifiers. Although these attacks are effective, they generate perturbations containing clearly discernible patterns such as sawtooth and spikes. Adversarial patterns are not perceptible on images, but the attacks proposed to date are readily perceptible in the case of time series. In order to generate stealthier adversarial attacks for time series, we propose a new attack that produces smoother perturbations. We introduced a function to measure the smoothness for time series. Using it, we find that smooth perturbations are harder to detect both visually, by the naked eye and by deep learning models. We also show two ways of protection against adversarial attacks: the first one by detecting the attacks using a deep model; the second one by using adversarial training to improve the robustness of a model against a specific attack, thus making it less vulnerable.
Finite element analysis of a 108-year-old unreinforced brick masonry tower following the 2015 Nepal earthquakes
Authors: Kumar Ambareesh , Pallav Kumar
Published: October 2023

After a visual inspection following the 2015 Nepal earthquakes, a finite element analysis (FEA) was conducted on a 108-year-old unreinforced brick masonry tower. The focus of study was on the brick masonry clock tower standing at a height of 30.48 m on the Senate Hall (SH) building of Allahabad University in India. This tower, which spans five storeys and features a rectangular cross-sectional shape, exhibits substantial cracks and material degradation across its connections and binding points. The process involved creating geometric plans and a 3D finite-element model through visual inspection and implementing ANSYS Workbench. The study utilised the mechanical properties of the aged materials, sourced from various studies encompassing surveys of old monumental structures, codes, and historical records. The clock tower’s behaviour was assessed through static, modal, and site-specific simulated time history analyses. The static analysis results revealed a maximum deflection of 3.76 mm at the top and a maximum equivalent (von-Mises) stress of 1.81 MPa at the joint of the first-floor level. Modal frequencies for the first three modes were determined to understand the tower’s free vibration behaviour. The time history analyses presented the acceleration, velocity, and displacement response under a peak ground acceleration (PGA) of 1.29 m/s2 simulated for the site. The dynamic analysis highlighted stress responses in critical locations, exposing severe cracks and damages across various points.
WHO Goals and Beyond: Managing HIV/TB Co-infection in South Africa
Authors: Olivier Cara , Luies Laneke
Published: October 2023

The intricate relationship between HIV and TB, particularly in South Africa which grapples with an alarming prevalence of both diseases, presents a multifaceted challenge influenced by historical, social, and biological factors. This review explores the co-dependent nature of these diseases and the challenges to effective control strategies. The ramifications of Apartheid significantly shaped these pandemics, with TB thriving in impoverished conditions marked by overcrowding and limited health care access. Co-infection intensifies health challenges, further complicating treatment and management. Despite commendable efforts, achieving the ambitious “End TB” and “End HIV” goals set by the World Health Organization (WHO) for 2030 remains intricate due to socio-economic disparities, health care constraints, and political dynamics. The recent emergence of the COVID-19 pandemic introduced additional complexities, disrupting diagnostic and treatment services. Nevertheless, South Africa’s resilience is evident through destigmatisation campaigns, innovative preventative interventions, and significant contributions to global research. The importance of prevalence studies cannot be overstated; accurate data collection and analysis remain pivotal for informed interventions and tracking progress towards WHO goals. Here, we elucidate the need for a unified and comprehensive national response, supported by international collaboration, to effectively address the enduring HIV and TB burden within South Africa. As the nation navigates intricate historical legacies, social factors, and evolving health challenges, a crucial question arises: Will South Africa ultimately meet the WHO’s elimination goals or at least reduce the number of HIV-related TB deaths? Recognising potential obstacles, it becomes imperative to strategise responses to enable effective syndemic management and advancement towards WHO’s objectives.
A Rare Histopathological Diagnosis: Endometrioid Adenocarcinoma Localized in the Rectum: a Case Report
Authors: Pace Marco , Carillo Giovanna , Paolo Marco Di Giovan , Stipa Francesco
Published: October 2023

Endometriosis-associated intestinal tumors represent malignant transformation of gastrointestinal endometriosis. Clinical features are similar to colon tumor with abdominal or pelvic pain, dyschezia, or bloody stools. Intestinal occlusion or perforation has also been described as a first presentation. The diagnosis is often postoperative, and it is based on specific immunohistochemical patterns (CK7+/CK20−). We present a rare case of a woman with a malignant transformation of an endometriotic lesion of the sigmoid colon, who underwent emergency surgery for intestinal occlusion. She underwent an exploratory laparotomy and Hartmann resection. The immunophenotypic analysis of the specimens revealed the following pattern: CK20−, CK7+, compatible with the diagnosis of endometrioid adenocarcinoma. Endometrioid carcinoma is a rare tumor, difficult to diagnose preoperatively because of similar symptoms of sigmoid carcinoma. A high index of suspicion in conjunction with careful histological and immunohistochemical examination (CK7, CK20, CDX2, CD10, ER, and PR) is important for establishing a correct diagnosis.
Enforceable Duties: Cicero and Kant on the Legal Nature of Political Order
Authors: Straumann Benjamin
Published: October 2023

This article seeks to show the importance of Cicero for Kant by pointing out the systematic relationship between their respective views on ethics and law. Cicero was important to Kant because Cicero had already elaborated an imperative, “quasi-jural” conception of duty or obligation. Cicero had also already prefigured the distinction between ethical duties and duties of justice. The article does not establish any direct historical influence, but points out interesting systematic overlaps. The most important in the realm of ethics are a universal rationalism; a rule-based normative framework of duty; and skepticism about (Cicero), or rejection of (Kant), eudaimonism. In the realm of political theory, it is the centrality of law and of property that unites both thinkers; both reject voluntarism in thinking that consensus flows from the right external laws, not the other way around, and thus creates a juridical community; and lastly, both Cicero and Kant believe that transparence, or publicity, is a key ideal that might be presupposed by both the ethical and the juridical domain. The article thus shows that both Cicero and Kant separate ethics from law, but there are indications that neither has given up the aspiration to bridge the two realms on a higher plane. This reading of Kant yields both a more Ciceronian Kant and allows us to perceive Kantian aspects of Cicero.
The effect of economic conditions on poverty perception in Minnesota
Authors: Siposné Nándori Eszter , Roufs Timothy G.
Published: October 2023

The paper analyzes subjective poverty in St. Louis County, Minnesota, with the methods of systematic data collection in 2020 and makes a diachronic comparison using the results of a similar survey from 2010. The paper identifies the most important poverty-related items and compares the precise meanings of the results of the 2010 and 2020 surveys. It also aims to find out how the recovery after the recession of 2008 modified perceptions of poverty. It is revealed that poverty in 2020 is mainly associated with items related to material needs. Many of the items mentioned in relation to poverty are related to financial issues, to basic human needs, or to physical safety. The paper concludes that in spite of the economic recovery, subjective poverty did not change significantly in the examined period.
Employing plant DNA barcodes for pomegranate species identification in Al-Baha Region, Saudi Arabia
Authors: Omari Alzahrani Fatima , Dguimi Houda Maaroufi , Alshaharni Mohammed O. , Albalawi Doha , Zaoui Sonia
Published: October 2023

The Punica granatum (Pomegranate) tree attracted a lot of interest for its nutritious fruits and therapeutic benefits. Although research on genetic diversity is important to develop breeding programs and implement efficient cultivar improvement, the genetic diversity of pomegranates in Saudi Arabia has not been investigated completely. The two important pomegranate cultivars in Al-Baha region of Saudi Arabia (Bidah-red and Bidah-green), which have recently gained considerable attention due to their unique sweet taste, were studied using DNA barcodes because information about their phylogeny is limited. To reveal the phylogeny of these two cultivars, three DNA barcodes [the internal transcribed spacer 2 (ITS2), ribulose 1,5-biphosphate carboxylase (rbcL), and intergenic spacer region (trnH-psbA)] were used. The ITS2 and psbA-trnH had sufficient polymorphism to allow distinction at the cultivar level, whereas the rbcL region had a uniform sequence; hence, it failed to discriminate among the cultivars. The two cultivars were found to be clustered in the same clade on the phylogenetic tree constructed using the ITS2 and psbA-trnH sequences, suggesting that they are either closely related or have adapted to their locations. As the ITS2 region exhibited higher polymorphism than psbA-trnH, the phylogenetic tree based on ITS2 indicated that Bidah-red and Bidah-green are distinct cultivars. We conclude that ITS2 and psbA-trnH DNA barcodes are capable of authenticating and identifying pomegranate cultivars and can assist in improving pomegranate quality in the future through molecular breeding.
The metaphysics of personhood in Confucian role ethics
Authors: Wang Jennifer
Published: October 2023

Inspired by early Confucian texts such as the Analects, Mencius, and Xunzi, defenders of Confucian role ethics argue that persons are constituted by their social roles and relationships. However, this has the puzzling implication that persons cannot survive changes in social roles and relationships. This paper proposes ways to understand this claim by appealing to the notions of essence, material constitution, and four-dimensionalism. In particular, it will be suggested that role ethicists should distinguish biological humans from persons and should say either that (i) persons are materially constituted by biological humans, or that (ii) persons are four-dimensional objects that merely overlap with biological humans. There has thus far not been much contact between early Chinese philosophy and contemporary metaphysics in this vein. A secondary goal of this paper is to demonstrate that views in early Chinese philosophy can be examined within frameworks from contemporary metaphysics, and furthermore, that the results include novel theses not yet recognized in contemporary metaphysics.
The Support to Mitigate the Impact of Suicide for Disaster Aid Workers of the 2011 Great East Japan Earthquake
Authors: Fukuchi Naru , Shigemura Jun , Obara Akiko
Published: October 2023

Suicide substantially impacts disaster-affected communities due to pre-existing psychosocial effects caused by the disaster. Following the Great East Japan Earthquake of 2011, local disaster aid workers had overworked for months, and many workers eventually died by suicide. Although many workplaces suffered this dual damage, there is limited literature on psychosocial postvention in this context. This study reports the activities of individual/group postventions provided to these aid workers. The bereaved person expressed grief for the loss of their colleagues and anger for not being protected. The postvention observed unusual and distinctive group dynamics. It was essential for mental health professionals to address 2 types of traumatic exposures in the group programs —trauma from the disaster and their colleagues’ deaths due to suicide. These postvention programs might be beneficial in maintaining aid workers’ mental health and helping them cope with the loss of their colleagues.
The Rule-of-Law as a Problem Space: Wāsṭa and the Paradox of Justice in Jordan
Authors: Doughan Yazan
Published: October 2023

This article explores structural entanglements between the rule-of-law, as a globalized aspirational horizon in post-Cold War politics, and corruption, as a highly salient malaise, by way of an ethnography of wāsṭa, an institutionalized practice of patronage in Jordan, and a salient object of corruption discourse in recent years. The article follows wāsṭa and anti-corruption practices in various sites where wāsṭa is most salient and most problematized and situates the contemporary practice in relation to historical transformations in Jordan’s political economy and global discourses on justice and development. While globalized anti-corruption discourses pit practices of patronage and brokerage like wāsṭa against the rule-of-law, an ethnographic and historical view illustrates how the latter is the condition of possibility of the former, the framework by which it is diagnosed, and its presumed cure. Thus, I argue that the rule-of-law should be understood as a historically specific “problem space” that posits corruption as a prime diagnostic of the ills of state and society while generating practical paradoxes and a perpetual sense of temporal out-of-jointedness for “developing” countries.
Precedent and Fairness
Authors: Perry Adam
Published: October 2023

Courts in common law systems decide cases as they decided like cases in the past—even if they believe they decided those past cases wrongly. What, if anything, justifies this practice? I defend two main claims. The first is that fairness favors treating like cases alike if that means treating them correctly. The second is that, in general, a court is as likely to decide an instant case correctly as it was to decide a previous and like case correctly. Together, these claims tell us that departing from and following precedent are equally likely to yield a correct decision, whereas following precedent may also yield a fair decision. Adhering to precedent is the dominant alternative, as a result. Fairness therefore justifies the practice of precedent. While this conclusion is not original, my argument for it is.
The role of primary health care in long-term care facilities during the COVID-19 pandemic in 30 European countries: a retrospective descriptive study (Eurodata study)
Authors: Guisado-Clavero Marina , Ares-Blanco Sara , Serafini Alice , Del Rio Lourdes Ramos , Larrondo Ileana Gefaell , Fitzgerald Louise , Vinker Shlomo , van Pottebergh Gijs , Valtonen Kirsi , Vaes Bert , Yilmaz Canan Tuz , Torzsa Péter , Tilli Paula , Sentker Theresa , Seifert Bohumil , Saurek-Aleksandrovska Natalija , Sattler Martin , Petricek Goranka , Petrazzuoli Ferdinando , Petek Davorina , Perjés Ábel , López Naldy Parodi , Neves Ana Luisa , Murauskienė Liubovė , Lingner Heidrun , Nessler Katarzyna , Heleno Bruno , Krztoń-Królewiecka Anna , Kostić Milena , Korkmaz Büsra Çimen , Knežević Snežana , Kirkovski Aleksandar , Karathanos Vasilis Trifon , Jandrić-Kočić Marijana , Ivanna Shushman , Ільков Оксана , Hoffmann Kathryn , Hanževački Miroslav , Gómez-Johansson Mila , Gjorgjievski Dragan , Domeyer Philippe-Richard J. , Peña Maryher Delphin , Divjak Asja Ćosić , Busneag Iliana-Carmen , Brutskaya-Stempkovskaya Elena , Bayen Sabine , Bakola Maria , Adler Limor , Assenova Radost , Astier-Peña María Pilar , Gómez Bravo Raquel
Published: October 2023

Background and aim:

Primary health care (PHC) supported long-term care facilities (LTCFs) in attending COVID-19 patients. The aim of this study is to describe the role of PHC in LTCFs in Europe during the early phase of the pandemic.

Methods:

Retrospective descriptive study from 30 European countries using data from September 2020 collected with an ad hoc semi-structured questionnaire. Related variables are SARS-CoV-2 testing, contact tracing, follow-up, additional testing, and patient care.

Results:

Twenty-six out of the 30 European countries had PHC involvement in LTCFs during the COVID-19 pandemic. PHC participated in initial medical care in 22 countries, while, in 15, PHC was responsible for SARS-CoV-2 test along with other institutions. Supervision of individuals in isolation was carried out mostly by LTCF staff, but physical examination or symptom’s follow-up was performed mainly by PHC.

Conclusion:

PHC has participated in COVID-19 pandemic assistance in LTCFs in coordination with LTCF staff, public health officers, and hospitals.
Tilted pulse front pumping techniques for efficient terahertz pulse generation
Authors: Tóth György , Polónyi Gyula , Hebling János
Published: October 2023

Optical rectification of femtosecond laser pulses has emerged as the dominant technique for generating single- and few-cycle terahertz (THz) pulses. The advent of the tilted pulse front pumping (TPFP) velocity matching technique, proposed and implemented two decades ago, has ushered in significant advancements of these THz sources, which are pivotal in the realm of THz pump-probe and material control experiments, which need THz pulses with microjoule energies and several hundred kV/cm electric field strengths. Furthermore, these THz sources are poised to play a crucial role in the realization of THz-driven particle accelerators, necessitating millijoule-level pulses with tens of MV/cm electric field strengths. TPFP has enabled the efficient velocity matching in lithium niobate crystals renowned for their extraordinary high nonlinear coefficient. Moreover, its adaptation to semiconductor THz sources has resulted in a two-hundred-times enhancement in conversion efficiency. In this comprehensive review, we present the seminal achievements of the past two decades. We expound on the conventional TPFP setup, delineate its scaling limits, and elucidate the novel generation TPFP configurations proposed to surmount these constraints, accompanied by their preliminary outcomes. Additionally, we provide an in-depth analysis of the THz absorption, refractive index, and nonlinear coefficient spectra of lithium niobate and widely used semiconductors employed as THz generators, which dictate their suitability as THz sources. We underscore the far-reaching advantages of tilted pulse front pumping, not only for LN and semiconductor-based THz sources but also for selected organic crystal-based sources and Yb-laser-pumped GaP sources, previously regarded as velocity-matched in the literature.
Control of CD4+ T cells to restrain inflammatory diseases via eukaryotic elongation factor 2 kinase
Authors: Peng Hao-Yun , Wang Liqing , Das Jugal Kishore , Kumar Anil , Ballard Darby J. , Ren Yijie , Xiong Xiaofang , de Figueiredo Paul , Yang Jin-Ming , Song Jianxun
Published: October 2023

CD4+ T cells, particularly IL-17-secreting helper CD4+ T cells, play a central role in the inflammatory processes underlying autoimmune disorders. Eukaryotic Elongation Factor 2 Kinase (eEF2K) is pivotal in CD8+ T cells and has important implications in vascular dysfunction and inflammation-related diseases such as hypertension. However, its specific immunological role in CD4+ T cell activities and related inflammatory diseases remains elusive. Our investigation has uncovered that the deficiency of eEF2K disrupts the survival and proliferation of CD4+ T cells, impairs their ability to secrete cytokines. Notably, this dysregulation leads to heightened production of pro-inflammatory cytokine IL-17, fosters a pro-inflammatory microenvironment in the absence of eEF2K in CD4+ T cells. Furthermore, the absence of eEF2K in CD4+ T cells is linked to increased metabolic activity and mitochondrial bioenergetics. We have shown that eEF2K regulates mitochondrial function and CD4+ T cell activity through the upregulation of the transcription factor, signal transducer and activator of transcription 3 (STAT3). Crucially, the deficiency of eEF2K exacerbates the severity of inflammation-related diseases, including rheumatoid arthritis, multiple sclerosis, and ulcerative colitis. Strikingly, the use of C188-9, a small molecule targeting STAT3, mitigates colitis in a murine immunodeficiency model receiving eEF2K knockout (KO) CD4+ T cells. These findings emphasize the pivotal role of eEF2K in controlling the function and metabolism of CD4+ T cells and its indispensable involvement in inflammation-related diseases. Manipulating eEF2K represents a promising avenue for novel therapeutic approaches in the treatment of inflammation-related disorders.
Genomic and transcriptomic insights into complex virus–prokaryote interactions in marine biofilms
Authors: Zhou Kun , Wong Tin Yan , Long Lexin , Anantharaman Karthik , Zhang Weipeng , Wong Wai Chuen , Zhang Rui , Qian Pei-Yuan
Published: October 2023

Marine biofilms are complex communities of microorganisms that play a crucial ecological role in oceans. Although prokaryotes are the dominant members of these biofilms, little is known about their interactions with viruses. By analysing publicly available and newly sequenced metagenomic data, we identified 2446 virus–prokaryote connections in 84 marine biofilms. Most of these connections were between the bacteriophages in the Uroviricota phylum and the bacteria of Proteobacteria, Cyanobacteria and Bacteroidota. The network of virus–host pairs is complex; a single virus can infect multiple prokaryotic populations or a single prokaryote is susceptible to several viral populations. Analysis of genomes of paired prokaryotes and viruses revealed the presence of 425 putative auxiliary metabolic genes (AMGs), 239 viral genes related to restriction–modification (RM) systems and 38,538 prokaryotic anti-viral defence-related genes involved in 15 defence systems. Transcriptomic evidence from newly established biofilms revealed the expression of viral genes, including AMGs and RM, and prokaryotic defence systems, indicating the active interplay between viruses and prokaryotes. A comparison between biofilms and seawater showed that biofilm prokaryotes have more abundant defence genes than seawater prokaryotes, and the defence gene composition differs between biofilms and the surrounding seawater. Overall, our study unveiled active viruses in natural biofilms and their complex interplay with prokaryotes, which may result in the blooming of defence strategists in biofilms. The detachment of bloomed defence strategists may reduce the infectivity of viruses in seawater and result in the emergence of a novel role of marine biofilms.
Nucleophosmin 1 cooperates with BRD4 to facilitate c-Myc transcription to promote prostate cancer progression
Authors: Hong Zhe , Xu Chengdang , Zheng Shengfeng , Wang Xinan , Tao Yiran , Tan Yao , Lin Guowen , Wu Denglong , Ye Dingwei
Published: October 2023

Nucleophosmin 1 (NPM1) is a multifunctional protein that promotes tumor progression in various cancers and is associated with a poor prognosis of prostate cancer (PCa). However, the mechanism by which NPM1 exerts its malignant potential in PCa remains elusive. Here, we showed that NPM1 is overexpressed in PCa cell lines and tissues and that the dysregulation of NPM1 promotes PCa proliferation. We also demonstrated that NPM1 transcriptionally upregulates c-Myc expression in PCa cells that is diminished by blockade of bromodomain-containing protein 4 (BRD4). Furthermore, we detected a correlation between NPM1 and c-Myc in patient PCa specimens. Mechanistically, NPM1 influences and cooperates with BRD4 to facilitate c-Myc transcription to promote PCa progression. In addition, JQ1, a bromodomain and extra-terminal domain (BET) inhibitor, in combination with NPM1 inhibition suppresses PCa progression in vitro and in vivo. These results indicate that NPM1 promotes PCa progression through a c-Myc -mediated pathway via BRD4, and blockade of the NPM1–c-Myc oncogenic pathway may be a therapeutic strategy for PCa.
Classification of second harmonic generation effect in magnetically ordered materials
Authors: Xiao Rui-Chun , Shao Ding-Fu , Gan Wei , Wang Huan-Wen , Han Hui , Sheng Z. G. , Zhang Changjin , Jiang Hua , Li Hui
Published: October 2023

The relationship between magnetic order and the second harmonic generation (SHG) effect is a fundamental area of study in condensed matter physics with significant practical implications. In order to gain a clearer understanding of this intricate relation, this study presents a comprehensive classification scheme for the SHG effect in magnetically ordered materials. This framework offers a straightforward approach to connecting magnetic order and the SHG effect. The characteristics of the SHG tensors in all magnetic point groups are studied using the isomorphic group method, followed by a comprehensive SHG effect classification scheme that includes seven types based on the symmetries of the magnetic phases and their corresponding parent phases. In addition, a tensor dictionary containing the SHG and linear magneto-optic (LMO) effect is established. Furthermore, an extensive SHG database of magnetically ordered materials is also built up. This classification strategy exposes an anomalous SHG effect with even characteristics (i.e., invariant) under time-reversal symmetry, which is solely contributed by magnetic structure. Moreover, the proposed classification scheme facilitates the determination of magnetic structures through the SHG effect.
Anti-tumor activity of a recombinant measles virus against canine lung cancer cells
Authors: Tamura Kei , Fujiyuki Tomoko , Moritoh Kanako , Akimoto Hayato , Iizuka Keigo , Sato Hiroki , Asano Kazushi , Yoneda Misako , Kai Chieko
Published: October 2023

Canine primary lung cancer with metastasis has a poor prognosis with no effective treatment. We previously generated a recombinant measles virus (MV) that lost binding affinity to a principal receptor, SLAM, to eliminate its virulence as a new cancer treatment strategy. The virus, rMV-SLAMblind, targets nectin-4, recently listed as a tumor marker, and exerts antitumor activity against nectin-4-positive canine mammary cancer and urinary bladder transitional cell carcinoma cells. However, the effectivity of rMV-SLAMblind for other types of canine cancers is still unknown. Here we evaluated the antitumor effect of rMV-SLAMblind to canine lung cancer. Nectin-4 is expressed on three canine lung cancer cell lines (CLAC, AZACL1, AZACL2) and rMV-SLAMblind was able to infect these cell lines. CLAC cells showed reduced cell viability after virus infection. In the CLAC xenograft nude mouse model, intratumoral administration of rMV-SLAMblind significantly suppressed tumor growth. In rMV-SLAMblind-treated mice, natural killer cells were activated, andCxcl10andIl12alevels were significantly increased in comparison with levels in the control group. In addition, the depletion of NK cells reduced the anti-tumor effect. To understand difference in efficacy among canine lung cancer cell lines, we compared virus growth and gene expression pattern after virus treatment in the three canine lung cancer cell lines; virus growth was highest in CLAC cells compared with the other cell lines and the induction of interferon (IFN)-beta and IFN-stimulated genes was at lower levels in CLAC cells. These results suggested that rMV-SLAMblind exhibits oncolytic effect against some canine lung cancer cells and the cellular response after the virus infection may influence its efficacy.
Single-shot X-ray absorption spectroscopy at X-ray free electron lasers
Authors: Harmand Marion , Cammarata Marco , Chollet Matthieu , Krygier Andrew G. , Lemke Henrik T. , Zhu Diling
Published: October 2023

X-ray Absorption Spectroscopy (XAS) is a widely used X-ray diagnostic method for studying electronic and structural properties of matter. At first glance, the relatively narrow bandwidth and the highly fluctuating spectral structure of X-ray Free Electron Lasers (XFEL) sources seem to require accumulation over many shots to achieve high data quality. To date the best approach to implementing XAS at XFEL facilities has been using monochromators to scan the photon energy across the desired spectral range. While this is possible for easily reproducible samples such as liquids, it is incompatible with many important systems. Here, we demonstrate collection of single-shot XAS spectra over 10s of eV using an XFEL source, with error bars of only a few percent. We additionally show how to extend this technique over wider spectral ranges towards Extended X-ray Absorption Fine Structure measurements, by concatenating a few tens of single-shot measurements. Our results pave the way for future XAS studies at XFELs, in particular those in the femtosecond regime. This advance is envisioned to be especially important for many transient processes that can only be initiated at lower repetition rates, for difficult to reproduce excitation conditions, or for rare samples, such as those encountered in high-energy density physics.
Response of soil bacteria on habitat-specialization and abundance gradient to different afforestation types
Authors: Qiu Zhenlu , Li Jie , Wang Peng , Wang Dong , Han Li , Gao Xiaojuan , Shu Jing
Published: October 2023

Studies involving response of subgroups of soil microorganisms to forest change, especially comparative studies on habitat-specialization and abundance gradient were still lack. In this study, we analyzed the response of soil bacterial diversity and structure to afforestation types and its relationship to environment of Fanggan ecological restoration area under the classification of subgroups by habitat-specialization and abundance gradient based on abundance ratio respectively. The results were: (1) On the habitat-specialization gradient, the variation of OTUs species number and abundance was consistent and positively correlated with habitat-specialization; on the abundance gradient, the variation was opposite and OTUs species number was negatively correlated with abundance gradient; (2) The distribution frequency of each subgroup on both gradients was the highest in broad-leaved forests, but the abundance was the opposite. The distribution frequency of the same stand showed no difference among habitat-specialization subgroups, but the abundant subgroup in broad-leaved forests was the highest among the abundance subgroups; (3) α-diversity was positively correlated with habitat-specialization but negatively with abundance, with the highest mostly in broad-leaved and mixed forests; (4) Community structure among stands on habitat-specialization gradient showed no significant difference, but that of rare subgroup between broad-leaved forests and other stands significantly differed. Plant diversity and vegetation composition correlated stronger with community structure than spatial distance and soil physicochemical properties on both gradients. Our results provided a new perspective for revealing the effects of afforestation types on soil bacteria from the comparison of habitat specialization and abundance gradient.
Optimization of Plasmodium vivax infection of colonized Amazonian Anopheles darlingi
Authors: Andrade Alice O. , Santos Najara Akira C. , Bastos Alessandra S. , Pontual José Daniel C. , Araújo Cristiane S. , Lima Analice S. , Martinez Leandro N. , Ferreira Amália S. , Aguiar Anna Caroline C. , Teles Carolina B. G. , Guido Rafael V. C. , Santana Rosa A. , Lopes Stefanie C. P. , Medeiros Jansen F. , Rizopoulos Zaira , Vinetz Joseph M. , Campo Brice , Lacerda Marcus Vinicius G. , Araújo Maisa S.
Published: October 2023

Obtaining Plasmodium vivax sporozoites is essential for in vitro culture of liver stage parasites, not only to understand fundamental aspects of parasite biology, but also for drug and vaccine development. A major impediment to establish high-throughput in vitro P. vivax liver stage assays for drug development is obtaining sufficient numbers of sporozoites. To do so, female anopheline mosquitoes have to be fed on blood from P. vivax-infected patients through an artificial membrane-feeding system, which in turns requires a well-established Anopheles colony. In this study we established conditions to provide a robust supply of P. vivax sporozoites. Adding a combination of serum replacement and antibiotics to the membrane-feeding protocol was found to best improve sporozoite production. A simple centrifugation method appears to be a possible tool for rapidly obtaining purified sporozoites with a minimal loss of yield. However, this method needs to be better defined since sporozoite viability and hepatocyte infection were not evaluated.
Tomato defences modulate not only insect performance but also their gut microbial composition
Authors: Bosorogan Andreea , Cardenas-Poire Erick , Gonzales-Vigil Eliana
Published: October 2023

Plants protect their tissues from insect herbivory with specialized structures and chemicals, such as cuticles, trichomes, and metabolites contained therein. Bacteria inside the insect gut are also exposed to plant defences and can potentially modify the outcome of plant–insect interactions. To disentangle this complex multi-organism system, we used tomato mutants impaired in the production of plant defences (odorless-2 and jasmonic acid–insensitive1) and two cultivars (Ailsa Craig and Castlemart), exposed them to herbivory by the cabbage looper (Trichoplusia ni H.) and collected the insect frass for bacterial community analysis. While the epicuticular wax and terpene profiles were variable, the leaf fatty acid composition remained consistent among genotypes. Moreover, larval weight confirmed the negative association between plant defences and insect performance. The distinctive frass fatty acid profiles indicated that plant genotype also influences the lipid digestive metabolism of insects. Additionally, comparisons of leaf and insect-gut bacterial communities revealed a limited overlap in bacterial species between the two sample types. Insect bacterial community abundance and diversity were notably reduced in insects fed on the mutants, with Enterobacteriaceae being the predominant group, whereas putatively pathogenic taxa were found in wildtype genotypes. Altogether, these results indicate that plant defences can modulate insect-associated bacterial community composition.