bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of bromodomain and extra-terminal proteins targets constitutively active NFκB and STAT signaling in lymphoma and influences the expression of the antiapoptotic proteins BCL2A1 and c-MYC
Authors: Pieper Nadja M. , Schnell Julia , Bruecher Daniela , Knapp Stefan , Vogler Meike 
Published: August 2024

AbstractThe antiapoptotic protein BCL2A1 is highly, but very heterogeneously expressed in Diffuse Large B-cell Lymphoma (DLBCL). Particularly in the context of resistance to current therapies, BCL2A1 appears to play an important role in protecting cancer cells from the induction of cell death. Reducing BCL2A1 levels may have therapeutic potential, however, no specific inhibitor is currently available. In this study, we hypothesized that the signaling network regulated by epigenetic readers may regulate the transcription of BCL2A1 and hence that inhibition of Bromodomain and Extra-Terminal (BET) proteins may reduce BCL2A1 expression thus leading to cell death in DLBCL cell lines. We found that the mechanisms of action of acetyl-lysine competitive BET inhibitors are different from those of proteolysis targeting chimeras (PROTACs) that induce the degradation of BET proteins. Both classes of BETi reduced the expression of BCL2A1 which coincided with a marked downregulation of c-MYC. Mechanistically, BET inhibition attenuated the constitutively active canonical nuclear factor kappa-light-chain-enhancer of activated B-cells (NFκB) signaling pathway and inhibited p65 activation. Furthermore, signal transducer of activated transcription (STAT) signaling was reduced by inhibiting BET proteins, targeting another pathway that is often constitutively active in DLBCL. Both pathways were also inhibited by the IκB kinase inhibitor TPCA-1, resulting in decreased BCL2A1 and c-MYC expression. Taken together, our study highlights a novel complex regulatory network that links BET proteins to both NFκB and STAT survival signaling pathways controlling both BCL2A1 and c-MYC expression in DLBCL.
Graphical Abstract
1–10-100: Unifying goals to mobilize global action on antimicrobial resistance
Authors: Rogers Van Katwyk Susan , Poirier Mathieu J. P. , Chandy Sujith J. , Faure Kim , Fisher Caitlin , Lhermie Guillaume , Moodley Arshnee , Sarkar Satyajit , Sophie Masika , Strong Kayla , Weldon Isaac , Hoffman Steven J. 
Published: August 2024

AbstractThe Bellagio Group for Accelerating AMR Action met in April 2024 to develop the ambitious but achievable 1–10-100 unifying goals to galvanize global policy change and investments for antimicrobial resistance mitigation: 1 Health; 10 million lives saved; and 100% sustainable access to effective antimicrobials. High profile political goals such as the Paris Agreement’s objective to keep global warming well below 2° Celsius compared to pre-industrial levels, UNAIDS’ 90–90-90 goal, and the Sustainable Development Goals challenge global norms, direct attention towards relevant activities, and serve an energizing function to motivate action over an extended period of time. The 1–10-100 unifying goals propose to unite the world through a One Health approach to safeguard human health, animal welfare, agrifood systems, and the environment from the emergence and spread of drug-resistant microbes and infections; save over 10 million lives by 2040 through concerted efforts to prevent and appropriately treat infections while preserving the vital systems and services that depend on sustained antimicrobial effectiveness; and commit to ensuring that antimicrobials are available and affordable for all, used prudently, and secured for the future through innovation. Compared to existing technical targets, these unifying goals offer advantages of focusing on prevention, encouraging multisectoral action and collaboration, promoting health equity, recognizing the need for innovation, and integrating with Sustainable Development Goals. By committing to 1 Health, 10 million lives saved, and 100% sustainable access to effective antimicrobials, we can protect lives and livelihoods today and safeguard options for tomorrow.
“It's normal to be afraid”: attacks on healthcare in Ouaka, Haute-Kotto, and Vakaga prefectures of the Central African Republic, 2016–2020
Authors: Kostandova Natalya , OKeeffe Jennifer , Ali Blaise Bienvenu , Somsé Pierre , Mahieu Audrey , Bingou Odilon Guesset , Dackpa Sebastien , Mbonimpa Gerard , Rubenstein Leonard 
Published: August 2024

AbstractIntroductionAttacks on healthcare have further weakened the already fragile health system in the Central African Republic. We investigated attacks on healthcare in three conflict-affected prefectures—Ouaka, Haute-Kotto, and Vakaga—from 2016 to 2020. The study aim was to gain an in-depth understanding of the immediate and long-term effects of attacks on healthcare workers, facilities, supply chain, quality of care, and other components of the health system. We provide a qualitative description of the incidents, assess their impacts, identify mitigation efforts, and discuss challenges to recovery.MethodsWe used purposive and snowball sampling to identify participants in the study. Semi-structured key informant interviews were conducted with administrative and health authorities, front-line personnel, and staff of non-governmental organizations. Interviews were done in Sango, French, or English. Recorded interviews were transcribed and notes taken for non-recorded interviews. Transcripts and notes were analyzed using inductive coding, allowing participant responses to guide findings.ResultsOf 126 attacks identified over the study period, 36 key informants discussed 39 attacks. Attacks included killings, physical and sexual assault, abductions, arson, shelling with grenades, pillage, occupations, and verbal threats. The violence led to extended closures and debilitating shortages in healthcare services, disproportionately affecting vulnerable populations, such as children under five, or people who are elderly, chronically ill, or displaced. Healthcare workers faced psychological trauma and moral injury from repeated attacks and the inability to provide adequate care. Personnel and communities made enormous efforts to mitigate impacts, and advocate for assistance. They were limited by failed reporting mechanisms, ongoing insecurity, persistent lack of resources and external support.ConclusionEffective strategies to safeguard healthcare from violence exist but better support for communities and health workers is essential, including measures to assess needs, enhance security, and facilitate recovery by quickly rebuilding, resupplying, and re-staffing facilities. CAR’s government, international organizations, and donors should make concerted efforts to improve reporting mechanisms and end impunity for perpetrators. Their investment in community organizations and long-term health system support, especially for health worker training, salaries, and psychosocial care, are vital steps towards building resilience against and mitigating the impacts of attacks on healthcare.
Astrocyte-derived dominance winning reverses chronic stress-induced depressive behaviors
Authors: Noh Kyungchul , Oh Junyoung , Cho Woo-Hyun , Hwang Minkyu , Lee Sung Joong 
Published: August 2024

AbstractIndividuals with low social status are at heightened risk of major depressive disorder (MDD), and MDD also influences social status. While the interrelationship between MDD and social status is well-defined, the behavioral causality between these two phenotypes remains unexplored. Here, we investigated the behavioral relationships between depressive and dominance behaviors in male mice exposed to chronic restraint stress and the role of medial prefrontal cortex (mPFC) astrocytes in these behaviors. Chronic restraint stress induced both depressive and submissive behaviors. Chemogenetic mPFC astrocyte activation significantly enhanced dominance in chronic stress-induced submissive mice by increasing the persistence of defensive behavior, although it did not affect depressive behaviors. Notably, repetitive winning experiences following mPFC astrocyte stimulation exerted anti-depressive effects in chronic restraint stress-induced depressive mice. These data indicate that mPFC astrocyte-derived winning experience renders anti-depressive effects, and may offer a new strategy for treating depression caused by low status in social hierarchies by targeting mPFC astrocytes.
Non-invasive versus arterial pressure monitoring in the pre-hospital critical care environment: a paired comparison of concurrently recorded measurements
Authors: Perera Yani , Raitt James , Poole Kurtis , Metcalfe David , Lewinsohn Asher 
Published: August 2024

Abstract
Background
Blood pressure monitoring is important in the pre-hospital management of critically ill patients. Non-invasive blood pressure (NIBP) measurements are commonly used but the accuracy of standard oscillometric cuff devices may be affected by extremes of physiology and adverse conditions (e.g. vibration) during transport. This study aimed to quantify the accuracy of NIBP measurements amongst patients requiring pre-hospital critical care.

Methods
A retrospective cohort study was undertaken using data from patients treated by a pre-hospital critical team between 1st May 2020 and 30th April 2023 that had NIBP measured concurrently with invasive blood pressure (IBP) arterial manometry. An acceptable difference was determined a priori to be < 20mmHg for systolic blood pressure (SBP) and diastolic blood pressure (DBP), and < 10mmHg for mean arterial pressure (MAP). The primary outcome was “pairwise agreement”, i.e. the proportion of paired observations that fell within this range of acceptability. Bland-Altman plots were constructed together with 95% limits of agreement to visualise differences between pairs of data. Associations with patient age, reason for critical care, transport status, haemodynamic shock, severe hypertension, and arterial catheter position were explored in univariate analyses and by fitting multivariable logistic regression models.

Results
There were 2,359 paired measurements from 221 individual patients with a median age of 57. The most frequent reason for transport was cardiac arrest (79, 35.7%). Bland-Altman analyses suggested unacceptably wide limits of agreement with NIBP overestimating both SBP and MAP during hypotension and underestimating these values during hypertension. Haemodynamic shock (SBP < 90mmHg) was independently associated with reduced pairwise agreement for SBP (adjusted odds ratio [aOR] 0.52, 95% CI 0.35 to 0.77), DBP (aOR 0.65, 95% CI 0.42 to 0.99) and MAP (aOR 0.53, 95% CI 0.36 to 0.78) and severe hypertension (SBP > 160mmHg) with reduced pairwise agreement for SBP (aOR 0.17, 95% CI 0.11 to 0.27). There was no association between patient transport and agreement between the methods for SBP, DBP, or MAP.

Conclusions
Non-invasive blood pressure measurements are often inaccurate in the pre-hospital critical care setting, particularly in patients with haemodynamic instability. Clinicians should be cautious when interpreting NIBP measurements and consider direct arterial pressure monitoring when circumstances allow.
Systematic assessment of HER2 status in ductal carcinoma in situ of the breast: a perspective on the potential clinical relevance
Authors: Van Bockstal Mieke R. , Wesseling Jelle , Lips Ester H. , Smidt Marjolein , Galant Christine , van Deurzen Carolien H. M. 
Published: August 2024

AbstractIn many countries, hormone receptor status assessment of ductal carcinoma in situ (DCIS) is routinely performed, as hormone receptor-positive DCIS patients are eligible for adjuvant anti-hormonal treatment, aiming to reduce the ipsilateral and contralateral breast cancer risk. Although HER2 gene amplification and its associated HER2 protein overexpression constitute a major prognostic and predictive marker in invasive breast carcinoma, its use in the diagnosis and treatment of DCIS is less straightforward. HER2 immunohistochemistry is not routinely performed yet, as the role of HER2-positivity in DCIS biology is unclear. Nonetheless, recent data challenge this practice. Here, we discuss the value of routine HER2 assessment for DCIS. HER2-positivity correlates strongly with DCIS grade: around four in five HER2-positive DCIS show high grade atypia. As morphological DCIS grading is prone to interobserver variability, HER2 immunohistochemistry could render grading more robust. Several studies showed an association between HER2-positive DCIS and ipsilateral recurrence risk, albeit currently unclear whether this is for overall, in situ or invasive recurrence. HER2-positive DCIS tends to be larger, with a higher risk of involved surgical margins. HER2-positive DCIS patients benefit more from adjuvant radiotherapy: it substantially decreases the local recurrence risk after lumpectomy, without impact on overall survival. HER2-positivity in pure biopsy-diagnosed DCIS is associated with increased upstaging to invasive carcinoma after surgery. HER2 immunohistochemistry on preoperative biopsies might therefore provide useful information to surgeons, favoring wider excisions. The time seems right to consider DCIS subtype-dependent treatment, comprising appropriate local treatment for HER2-positive DCIS patients and de-escalation for hormone receptor-positive, HER2-negative DCIS patients.
Insights into the m6A demethylases FTO and ALKBH5 : structural, biological function, and inhibitor development
Authors: Gao Zewei , Zha Xuan , Li Min , Xia Xueli , Wang Shengjun 
Published: August 2024

AbstractN6-methyladenosine (m6A) is dynamically regulated by methyltransferases (termed “writers”) and demethylases (referred to as “erasers”), facilitating a reversible modulation. Changes in m6A levels significantly influence cellular functions, such as RNA export from the nucleus, mRNA metabolism, protein synthesis, and RNA splicing. They are intricately associated with a spectrum of pathologies. Moreover, dysregulation of m6A modulation has emerged as a promising therapeutic target across many diseases. m6A plays a pivotal role in controlling vital downstream molecules and critical biological pathways, contributing to the pathogenesis and evolution of numerous conditions. This review provides an overview of m6A demethylases, explicitly detailing the structural and functional characteristics of FTO and ALKBH5. Additionally, we explore their distinct involvement in various diseases, examine factors regulating their expression, and discuss the progress in inhibitor development.
Low-complexity cooperative active and passive beamforming multi-RIS-assisted communication networks
Authors: Elsherbini Mostafa M. , Omer Osama A. , Salah Mostafa 
Published: August 2024

AbstractReconfigurable intelligent surface (RIS) is a groundbreaking technology that has a significant potential for sixth generation (6G) networks. Its unique capability to control wireless environments makes it an attractive option. However, the spatial diversity increased by assisting users with all deployed RISs, this investigation has two drawbacks the high complexity design, and the received signals by the far RISs are severely attenuated. Therefore, we propose a RIS selection strategy to select the proper RISs as a pre-stage before the joint beamforming between the base station (BS) and RISs to reduce the high complexity of joint beamforming optimization. Furthermore, the joint active and passive beamforming problem based on the selection is formulated. Hence, achieving spatial diversity by examining cooperation between passive beamforming of multi-hop RIS, leads to a challenging problem. To tackle this issue, we design an algorithm for the RIS selection scheme. Also, to relax the non-convexity of the proposed problem, we decouple the problem into solvable subproblems by utilizing the fractional programming (FP) and quadratic transform (QT) optimization methods. Simulation results have demonstrated through different user locations the effectiveness of the selection strategy in performance enhancement by 30% in the sum rate, besides an obvious reduction in the complexity cost than other techniques.
Policy brief of the Belgian Europe’s Beating Cancer Plan mirror group: children, adolescents and young adults with cancer
Authors: Poirel Hélène A. , Schittecatte Gabrielle , Van Aelst Fabienne ,   on behalf of the Thematic Working Group (TWG) ‘Children, Adolescents and Young Adults (CAYAs) with Cancer’, Vandermeulen Ad , Gerbaux Alice , Amorim Christiani Andrade , Van Damme An , Uyttebroeck Anne , Brichard Benedicte , De Wilde Bram , Gunst Brecht , Stals Caroline , De Witte Chloë , Jungels Christiane , Devalck Christine , Geurten Claire , Dierickx Daan , Bogaert Delfien , Heenen Delphine , Romaen Elien , Balducci Elisa , Van Valckenborgh Els , Lippens Evi , Dequiedt Franck , Levy Gabriel , Neefs Hans , Segers Heidi , Chiairi Ibrahim , Demeestere Isabelle , De Munter Johan , Verlooy Joris , Messiaen Julie , Lemiere Jurgen , Van Beek Karen , Vandenabeele Karen , Maes Katrien , Dubois Kleo , Polastro Laura , Van Camp Laurens , Van De Voorde Lien , Lapeire Lore , Le Roux Manon , Chavez Marcela , Condorelli Margherita , Caillier Marie , Vander Haegen Marie , Van Damme Nancy , Belpame Nathalie , Kholmanskikh Olga , Bartoszk Paulina , Mazilier Pauline , Mayeur Pierre , Philippet Pierre , Vandekeere Saar , Verschueren Sabine , Jacobs Sandra , Moreels Sofie , Gijssels Stefan , Boterberg Tom , Van Genechten Toon , Albarani Valentina 
Published: August 2024

AbstractChildren and Adolescents and Young Adults with cancer represent a young population with specific needs, which need to be addressed in a patient- and cancer-driven way. There is an urgent need to support and extend the ongoing initiatives in Belgium. First, multidisciplinary care programmes dedicated to children need to be reviewed, and those for Adolescents and Young Adults need to be developed with close collaboration between paediatric and adult oncology and haematology teams. This needs to be done considering the entire patient journey; from cancer prevention, diagnosis, treatment, rehabilitation, follow-up of late effects, transition pathways between paediatric and adult wards, and palliative care. Second, national haemato/oncology precision programmes adapted to this young population with rare cancers, including infrastructure to manage cancer gene predisposition in CAYAs with cancers and their relatives, needs to be developed. This multi-level plan aims to ensure improved outcome with high quality of care for the young population with cancer in Belgium in line with Europe’s Beating Cancer Plan initiatives.
Hybrid nanostructures for neurodegenerative disease theranostics: the art in the combination of biomembrane and non-biomembrane nanostructures
Authors: Gao Chao , Xiong Ran , Zhang Zhi-yu , Peng Hua , Gu Yuan-kai , Xu Wei , Yang Wei-ting , Liu Yan , Gao Jie , Yin You 
Published: August 2024

AbstractThe diagnosis of neurodegenerative diseases (NDDs) remains challenging, and existing therapeutic approaches demonstrate little efficacy. NDD drug delivery can be achieved through the utilization of nanostructures, hence enabling multimodal NDD theranostics. Nevertheless, both biomembrane and non-biomembrane nanostructures possess intrinsic shortcomings that must be addressed by hybridization to create novel nanostructures with versatile applications in NDD theranostics. Hybrid nanostructures display improved biocompatibility, inherent targeting capabilities, intelligent responsiveness, and controlled drug release. This paper provides a concise overview of the latest developments in hybrid nanostructures for NDD theranostics and emphasizes various engineering methodologies for the integration of diverse nanostructures, including liposomes, exosomes, cell membranes, and non-biomembrane nanostructures such as polymers, metals, and hydrogels. The use of a combination technique can significantly augment the precision, intelligence, and efficacy of hybrid nanostructures, therefore functioning as a more robust theranostic approach for NDDs. This paper also addresses the issues that arise in the therapeutic translation of hybrid nanostructures and explores potential future prospects in this field.
The impact of hygienic living conditions on the differentiation of male body height at the beginning of the twentieth century in the USSR
Authors: Lebedeva Lidia , Godina Elena 
Published: August 2024

Abstract
Background
The positive changes in hygienic living conditions are commonly believed to explain secular changes in body height and the age of maturity. However, it is difficult to estimate the separate impacts of these factors due to the lack of social and economic data and variations in the sources of information.
We hypothesized that final male body height could be associated with various socioeconomic indicators, such as the development of the medical care system, the quality of nutrition, and the level of sanitary and hygienic conditions. Moreover, we hypothesized that male body height could be associated with the level of morbidity in the region during the time of conscript childhood (from 1 to 7 years old).

Materials and methods
We used two main sources of information in the analyses. The first is the data from the Statistical Reference Book published by the Central Statistical Committee in 1929. The second is the annual data from the Statistical Reference Book published in the Russian Empire. Since the conscripts were born between 1906 and 1909, we used datasets from 1910 to 1913. To analyze the data, we used a method of analyzing interacting variables called St. Nicolas House Analysis (SNHA).

Results
Our analyses revealed direct associations between the morbidity of some diseases and male body height and other anthropometric parameters.

Conclusions
There are associations between conscript final body height and the morbidity of influenza, dysentery and some venereal diseases, such as chancroid and syphilis. There were no associations between conscript final body height and the level of morbidity during childhood. However, other final parameters, such as BMI, weight, and chest circumference, could be associated with the morbidity of malaria, scabies, scurvy, and scarlet fever during childhood. The prevalence of these diseases could be strongly connected with unfavorable living conditions. The results are similar for both urban and rural areas.
Genetic factors, risk prediction and AI application of thrombotic diseases
Authors: Wang Rong , Tang Liang V. , Hu Yu 
Published: August 2024

AbstractIn thrombotic diseases, coagulation, anticoagulation, and fibrinolysis are three key physiological processes that interact to maintain blood in an appropriate state within blood vessels. When these processes become imbalanced, such as excessive coagulation or reduced anticoagulant function, it can lead to the formation of blood clots. Genetic factors play a significant role in the onset of thrombotic diseases and exhibit regional and ethnic variations. The decision of whether to initiate prophylactic anticoagulant therapy is a matter that clinicians must carefully consider, leading to the development of various thrombotic risk assessment scales in clinical practice. Given the considerable heterogeneity in clinical diagnosis and treatment, researchers are exploring the application of artificial intelligence in medicine, including disease prediction, diagnosis, treatment, prevention, and patient management. This paper reviews the research progress on various genetic factors involved in thrombotic diseases, analyzes the advantages and disadvantages of commonly used thrombotic risk assessment scales and the characteristics of ideal scoring scales, and explores the application of artificial intelligence in the medical field, along with its future prospects.