bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementing the human right to science in the regulatory governance of artificial intelligence in healthcare
Authors: Ho Calvin W L 
Published: October 2023

Abstract
Artificial intelligence (AI) enables a medical device to optimize its performance through machine learning (ML), including the ability to learn from past experiences. In healthcare, ML is currently applied within controlled settings in devices to diagnose conditions like diabetic retinopathy without clinician input, for instance. In order to allow AI-based medical devices (AIMDs) to adapt actively to its data environment through ML, the current risk-based regulatory approaches are inadequate in facilitating this technological progression. Recent and innovative regulatory changes introduced to regulate AIMDs as a software, or ‘software as a medical device’ (SaMD), and the adoption of a total device/product-specific lifecycle approach (rather than one that is point-in-time) reflect a shift away from the strictly risk-based approach to one that is more collaborative and participatory in nature, and anticipatory in character. These features are better explained by a rights-based approach and consistent with the human right to science (HRS). With reference to the recent explication of the normative content of HRS by the Committee on Economic, Social and Cultural Rights of the United Nations, this paper explains why a rights-based approach that is centred on HRS could be a more effective response to the regulatory challenges posed by AIMDs. The paper also considers how such a rights-based approach could be implemented in the form of a regulatory network that draws on a ‘common fund of knowledges’ to formulate anticipatory responses to adaptive AIMDs. In essence, the HRS provides both the mandate and the obligation for states to ensure that regulatory governance of high connectivity AIMDs become increasingly collaborative and participatory in approach and pluralistic in substance.
Management of calcified right atrial myxoma extending into the inferior vena cava: a case report
Authors: Khan Mohammad Qaiser Aziz , Zaheer Amna , Yasir Sarib Bin , Fatima Ramsha , Anand Ayush 
Published: October 2023

Abstract
Cardiac myxomas can rarely involve the right atrium, get calcified and involve the inferior vena cava (IVC). Early surgical intervention is critical to prevent life-threatening complications. We presented the case of a 39-year-old male with fever, cough and shortness of breath for 1 week. Initial laboratory investigations revealed leucocytosis and thrombocytopenia. His electrocardiogram was normal, and his chest X-ray showed bilateral infiltrates. Based on the findings of a high-resolution chest computed tomography scan, echocardiography and cardiac magnetic resonance imaging, we made a provisional diagnosis of calcified right atrial myxoma extending up to the IVC. We managed the case with cardiopulmonary bypass via aortic cannulation followed by a right atriotomy. Post-operatively, the patient’s condition improved and was doing well on monthly follow-ups.
New transient ULX candidate in NGC 4254: evidence of circumbinary disc?
Authors: Allak Sinan 
Published: October 2023

ABSTRACT
This paper presents the identification of a new transient ultraluminous X-ray source (ULX) candidate (ULX-3) with reaching a peak luminosity of ∼4 × 1039 erg s−1 in NGC 4254 by using archival Chandra, Swift/X-Ray Telescope, Hubble Space Telescope, and JWST observations. From precise astrometric calculations, unique optical, near-infrared, and mid-infrared counterparts were found. The spectral energy distribution (SED) and colour–magnitude diagrams of counterparts of the new ULX candidate were plotted to constrain the nature of the possible donor star. Evidence of a circumbinary disc was found from its SED with two blackbody temperatures of 1000 and 200 K. Moreover, according to the X-ray hardness ratios, ULX-3 exhibits very hard to very soft transitions as seen in some high-mass X-ray binaries with Be-star donors. Moreover, ULX-3 varies by more than two orders of magnitude in the 0.3–10 keV energy band as seen in typical transient ULXs.
New insights on ν–DM interactions
Authors: Brax Philippe , van de Bruck Carsten , Valentino Eleonora Di , Giaré William , Trojanowski Sebastian 
Published: October 2023

ABSTRACT
We revisit the possibility of using cosmological observations to constrain models that involve interactions between neutrinos and dark matter. We show that small-scale measurements of the cosmic microwave background (CMB) with a few per cent accuracy are critical to uncover unique signatures from models with tiny couplings that would require a much higher sensitivity at lower multipoles, such as those probed by the Planck satellite. We analyse the high-multipole data released by the Atacama Cosmology Telescope, both independently and in combination with Planck and baryon acoustic oscillation measurements, finding a compelling preference for a non-vanishing coupling, $\log _{10}u_{\nu \textrm {DM}}=-5.20^{+1.2}_{-0.74}$ at 68 per cent confidence level. This aligns with other CMB-independent probes, such as Lyman-α. We illustrate how this coupling could be accounted for in the presence of dark matter interactions with a sterile neutrino.
Elevated A-to-I RNA editing in COVID-19 infected individuals
Authors: Merdler-Rabinowicz Rona , Gorelik David , Park Jiwoon , Meydan Cem , Foox Jonathan , Karmon Miriam , Roth Hillel S , Cohen-Fultheim Roni , Shohat-ophir Galit , Eisenberg Eli , Ruppin Eytan , Mason Christopher E , Levanon Erez Y 
Published: October 2023

Abstract
Given the current status of coronavirus disease 2019 (COVID-19) as a global pandemic, it is of high priority to gain a deeper understanding of the disease's development and how the virus impacts its host. Adenosine (A)-to-Inosine (I) RNA editing is a post-transcriptional modification, catalyzed by the ADAR family of enzymes, that can be considered part of the inherent cellular defense mechanism as it affects the innate immune response in a complex manner. It was previously reported that various viruses could interact with the host's ADAR enzymes, resulting in epigenetic changes both to the virus and the host. Here, we analyze RNA-seq of nasopharyngeal swab specimens as well as whole-blood samples of COVID-19 infected individuals and show a significant elevation in the global RNA editing activity in COVID-19 compared to healthy controls. We also detect specific coding sites that exhibit higher editing activity. We further show that the increment in editing activity during the disease is temporary and returns to baseline shortly after the symptomatic period. These significant epigenetic changes may contribute to the immune system response and affect adverse outcomes seen in post-viral cases.
Pathogenic signal peptide variants in the human genome
Authors: Gutierrez Guarnizo Sneider Alexander , Kellogg Morgana K , Miller Sarah C , Tikhonova Elena B , Karamysheva Zemfira N , Karamyshev Andrey L 
Published: October 2023

Abstract
Secreted and membrane proteins represent a third of all cellular proteins and contain N-terminal signal peptides that are required for protein targeting to endoplasmic reticulum (ER). Mutations in signal peptides affect protein targeting, translocation, processing, and stability, and are associated with human diseases. However, only a few of them have been identified or characterized. In this report, we identified pathogenic signal peptide variants across the human genome using bioinformatic analyses and predicted the molecular mechanisms of their pathology. We recovered more than 65 thousand signal peptide mutations, over 11 thousand we classified as pathogenic, and proposed framework for distinction of their molecular mechanisms. The pathogenic mutations affect over 3.3 thousand genes coding for secreted and membrane proteins. Most pathogenic mutations alter the signal peptide hydrophobic core, a critical recognition region for the signal recognition particle, potentially activating the Regulation of Aberrant Protein Production (RAPP) quality control and specific mRNA degradation. The remaining pathogenic variants (about 25%) alter either the N-terminal region or signal peptidase processing site that can result in translocation deficiencies at the ER membrane or inhibit protein processing. This work provides a conceptual framework for the identification of mutations across the genome and their connection with human disease.
Radiomic features define risk and are linked to DNA methylation attributes in primary CNS lymphoma
Authors: Nenning Karl-Heinz , Gesperger Johanna , Furtner Julia , Nemc Amelie , Roetzer-Pejrimovsky Thomas , Choi Seung-Won , Mitter Christian , Leber Stefan L , Hofmanninger Johannes , Klughammer Johanna , Ergüner Bekir , Bauer Marlies , Brada Martina , Chong Kyuha , Brandner-Kokalj Tanisa , Freyschlag Christian F , Grams Astrid , Haybaeck Johannes , Hoenigschnabl Selma , Hoffermann Markus , Iglseder Sarah , Kiesel Barbara , Kitzwoegerer Melitta , Kleindienst Waltraud , Marhold Franz , Moser Patrizia , Oberndorfer Stefan , Pinggera Daniel , Scheichel Florian , Sherif Camillo , Stockhammer Guenther , Stultschnig Martin , Thomé Claudius , Trenkler Johannes , Urbanic-Purkart Tadeja , Weis Serge , Widhalm Georg , Wuertz Franz , Preusser Matthias , Baumann Bernhard , Simonitsch-Klupp Ingrid , Nam Do-Hyun , Bock Christoph , Langs Georg , Woehrer Adelheid 
Published: October 2023

Abstract

Background
The prognostic roles of clinical and laboratory markers have been exploited to model risk in patients with primary CNS lymphoma, but these approaches do not fully explain the observed variation in outcome. To date, neuroimaging or molecular information is not used. The aim of this study was to determine the utility of radiomic features to capture clinically relevant phenotypes, and to link those to molecular profiles for enhanced risk stratification.

Methods
In this retrospective study, we investigated 133 patients across 9 sites in Austria (2005–2018) and an external validation site in South Korea (44 patients, 2013–2016). We used T1-weighted contrast-enhanced MRI and an L1-norm regularized Cox proportional hazard model to derive a radiomic risk score. We integrated radiomic features with DNA methylation profiles using machine learning-based prediction, and validated the most relevant biological associations in tissues and cell lines.

Results
The radiomic risk score, consisting of 20 mostly textural features, was a strong and independent predictor of survival (multivariate hazard ratio = 6.56 [3.64–11.81]) that remained valid in the external validation cohort. Radiomic features captured gene regulatory differences such as in BCL6 binding activity, which was put forth as testable treatment target for a subset of patients.

Conclusions
The radiomic risk score was a robust and complementary predictor of survival and reflected characteristics in underlying DNA methylation patterns. Leveraging imaging phenotypes to assess risk and inform epigenetic treatment targets provides a concept on which to advance prognostic modeling and precision therapy for this aggressive cancer.
Utilizing Ceftazidime/Avibactam Therapeutic Drug Monitoring in the Treatment of Neurosurgical Meningitis Caused by Difficult-to-Treat Resistant Pseudomonas aeruginosa and KPC-Producing Enterobacterales
Authors: Yasmin Mohamad , Nutman Amir , Wang Lu , Marshall Steven , Chen Ke , Wang Jiping , Yahav Dafna , Lupinsky Liad , Hujer Andrea M , Bhimraj Adarsh , van Duin David , Li Jian , Bonomo Robert A 
Published: October 2023

Abstract

Background
Central nervous system (CNS) infections caused by Klebsiella pneumoniae carbapenemase (KPC)–producing Enterobacterales and difficult-to-treat resistant (DTR) Pseudomonas aeruginosa represent a formidable clinical challenge. Antimicrobial regimens that efficiently penetrate the cerebrospinal fluid (CSF) and achieve sufficient concentrations associated with microbiologic and clinical cure are limited. We evaluated therapy with ceftazidime-avibactam (CAZ-AVI) in order to guide precise dosing in the treatment of CNS infections.

Methods
Therapeutic drug monitoring (TDM) was performed in 3 patients with health care–associated ventriculitis and meningitis (HAVM) using CAZ-AVI 2.5 g infused intravenously every 8 hours as standard and extended infusion. Simultaneous CSF and plasma samples were obtained throughout the dosing interval in each patient. Concentrations of CAZ and AVI were determined by liquid chromatography/mass spectrometry.

Results
Bacterial identification revealed KPC-producing Klebsiella pneumoniae (KPC-Kp), DTR Pseudomonas aeruginosa, and KPC-producing Enterobacter cloacae (KPC-Ent.c). All isolates were resistant to carbapenems. The minimum inhibitory concentrations (MICs) of CAZ-AVI were 0.25/4, 4/4, and 0.25/4 μg/mL, respectively. CAZ and AVI concentrations were determined in CSF samples ranging from 29.0 to 15.0 µg/mL (CAZ component) and 4.20 to 0.92 µg/mL (AVI component), respectively. AVI achieved concentrations ≥1 µg/mL in 11 out of 12 CSF samples collected throughout the dosing interval. Clinical and microbiologic cure were attained in all patients.

Conclusions
Postinfusion concentrations of CAZ-AVI were measured in plasma and CSF samples obtained from 3 patients with complicated CNS infections caused by antimicrobial-resistant isolates. The measured concentrations revealed that standard CAZ and AVI exposures sufficiently attained values correlating to 50% fT &gt; MIC, which are associated with efficient bacterial killing.
A comparative study of three modes of s-process nucleosynthesis in extremely metal-poor AGB stars
Authors: Yamada Shimako , Suda Takuma , Komiya Yutaka , Aikawa Masayuki , Fujimoto Masayuki Y 
Published: October 2023

Abstract
Carbon-enhanced metal-poor (CEMP) stars in the Galactic halo have a wide range of neutron-capture element abundance patterns. To identify their origin, we investigate three modes of s-process nucleosynthesis that have been proposed to operate in extremely metal-poor asymptotic giant branch (AGB) stars: convective 13C burning, which occurs when hydrogen is engulfed by helium-flash convection in low-mass AGB stars; convective 22Ne burning, which occurs in helium-flash convection of intermediate-mass AGB stars; and radiative 13C burning, which occurs in the 13C pocket that is formed during inter-pulse periods. We show that the production of s-process elements per iron seed (s-process efficiency) does not depend on metallicity below [Fe$/$H] = −2, because 16O in the helium zone dominates the neutron poison. The convective 13C mode can produce a variety of s-process efficiencies for Sr, Ba, and Pb, including the maxima observed among CEMP stars. The 22Ne mode only produces the lowest end of s-process efficiencies among CEMP models. We show that the combination of these two modes can explain the full range of observed enrichment of s-process elements in CEMP stars. In contrast, the 13C pocket mode can hardly explain the high level of enrichment observed in some CEMP stars, even if considering star-to-star variations of the mass of the 13C pocket. These results provide a basis for discussing the binary mass transfer origin of CEMP stars and their subgroups.
The NLR immune receptor ADR1 and lipase-like proteins EDS1 and PAD4 mediate stomatal immunity in Nicotiana benthamiana and Arabidopsis
Authors: Wang Hanling , Song Susheng , Gao Shang , Yu Qiangsheng , Zhang Haibo , Cui Xiulin , Fan Jun , Xin Xiufang , Liu Yule , Staskawicz Brian , Qi Tiancong 
Published: October 2023

Abstract
In the presence of pathogenic bacteria, plants close their stomata to prevent pathogen entry. Intracellular nucleotide-binding leucine-rich repeat (NLR) immune receptors recognize pathogenic effectors and activate effector-triggered immune responses. However, the regulatory and molecular mechanisms of stomatal immunity involving NLR immune receptors are unknown. Here, we show that the Nicotiana benthamiana RPW8-NLR central immune receptor ACTIVATED DISEASE RESISTANCE 1 (NbADR1), together with the key immune proteins ENHANCED DISEASE SUSCEPTIBILITY 1 (NbEDS1) and PHYTOALEXIN DEFICIENT 4 (NbPAD4), plays an essential role in bacterial pathogen- and flg22-induced stomatal immunity by regulating the expression of salicylic acid (SA) and abscisic acid (ABA) biosynthesis or response-related genes. NbADR1 recruits NbEDS1 and NbPAD4 in stomata to form a stomatal immune response complex. The transcription factor NbWRKY40e, in association with NbEDS1 and NbPAD4, modulates the expression of SA and ABA biosynthesis or response-related genes to influence stomatal immunity. NbADR1, NbEDS1, and NbPAD4 are required for the pathogen infection-enhanced binding of NbWRKY40e to the ISOCHORISMATE SYNTHASE 1 promoter. Moreover, the ADR1-EDS1-PAD4 module regulates stomatal immunity in Arabidopsis (Arabidopsis thaliana). Collectively, our findings show the pivotal role of the core intracellular immune receptor module ADR1-EDS1-PAD4 in stomatal immunity, which enables plants to limit pathogen entry.
Did California Act to Save Lives? AB 392 and fatal officer-involved shootings
Authors: Powell Zachary A 
Published: October 2023

Abstract
American police face considerable criticism from the public about the perceived unnecessary and excessive use of deadly force in civilian interactions. Police reform advocates often call for widespread change to reduce officer-involved shootings and other forms of deadly force. Some, such as California, pursued statewide legal interventions to limit police deadly force. AB 392, the California Act to Save Lives, changed the deadly force standard so that objectively reasonable officers, when considering the totality of circumstances, can only use deadly force when necessary to defend human life. The stricter standard was designed to limit officer deadly force and reduce civilian deaths so this paper considers the efficacy of AB 392 on the incidence of fatal force in California. The results of interrupted time series and synthetic control method (SCM) analyses find no evidence of a reduction in deadly force after the passage of AB 392. Any effort to change deadly force should be coupled with legislative changes and evidence-based practices. Policymakers, practitioners, and researchers will need to explore a multi-pronged approach to reduce deadly force encounters.
Potential effects of spirulina and date palm pollens on zinc oxide nanoparticles -induced hepatoxicity, oxidative stress, and inflammation in male albino rats
Authors: Al-Azhary Diaa B , Sawy Samar A , Fawzy Hassan Hanaa , Meligi Noha M 
Published: October 2023

AbstractIntroduction: The application of Zinc oxide nanoparticles (ZnO NPs) is substantially growing in industrial products. Therefore, humans are increasingly exposed to ZnO NPs daily due to their extensive range of applications, raising worries about their possible toxicity. Aim: In this study, the ameliorative effects of raw Phoenix dactylifera L. (date palm) pollens (DPP) and Spirulina platensis (SP) independently against ZnO NPS-induced hepatoxicity in male albino rats were examined. Methods: Six groups (6/group) of adult male albino rats received oral treatment using distilled water (control), SP (1000 mg/kg b. wt.), DPP (100 mg/kg b. wt.), ZnO NPs (100 mg/kg b. wt.), ZnO NPs +SP, and ZnO NPs + DPP respectively for 15 days. Results: The results of the biochemical investigation indicated that the administration of ZnO NPs substantially upregulated (p &lt; 0.05) transaminases, alkaline phosphatase, and bilirubin serum levels. Malondialdehyde and pro-inflammatory cytokine serum levels were also elevated after ZnO NPs administration. Simultaneously, the downregulated catalase and glutathione peroxidase serum activities were significantly suppressed in ZnO NPs treated rats. Moreover, exposure to ZnO NPs induced liver histopathological alterations. The administration of SP and DPP ameliorated the aforementioned effects caused by ZnO NPs. This result can be attributable to the downregulation of hepatic transaminases, alkaline phosphatase, and bilirubin in the serum and the antioxidation system's equilibration, thus alleviating the accumulation of reactive oxygen species. Conclusion: SP and DPP are natural antioxidants with the potential to eliminate inflammation as well as oxidative damage caused by ZnO NPs in hepatic tissue.
The Mechanisms of Luteolin in Treating COVID-19 Based on Bioinformatics Analysis and Molecular Docking
Authors: Rong Hechen , Zeng Yu , Zheng Nan , Wang Yiwei , Guo Zhonghong , Wang Kun , Huang Xiaoping 
Published: October 2023

Abstract
Luteolin is a natural flavonoid that has a variety of pharmacological activities, such as anti-inflammatory, anti-allergic, anti-bacterial, anti-viral, apoptosis inhibition, cell autophagy regulation, and anti-tumor activity. It is one of the main ingredients of an expert-recommended herbal formula for the prevention and treatment of coronavirus disease 2019 (COVID-19). This suggests that luteolin has strong pharmacological effects on the prevention and treatment of COVID-19. The aims of this study were to identify the molecular targets of luteolin and to infer the possible mechanisms by which it exerts its pharmacological effects. The GSE159787 data set was obtained from the Gene Expression Omnibus online database, and differentially expressed genes were analyzed. There were 22 upregulated differentially expressed genes enriched in the COVID-19 signaling pathway, suggesting that the upregulation of these genes may be closely related to the occurrence of COVID-19. Molecular docking results showed that luteolin had strong binding efficiency to 20 of these 22 key genes. Six of these genes (CFB, EIF2AK2, OAS1, MAPK11, OAS3, and STAT1) showed strong binding activity. Luteolin can regulate the COVID-19 signaling pathway by combining with these targets, which may have a therapeutic effect on COVID-19.
Nomogram for Predicting Viral Shedding Time of SARS-CoV-2 Delta Variant in Patients with COVID-19: A Retrospective Study
Authors: Zhou Jiejun , Fan Lin , Li Duo , Chen Mingwei , Yang Tian 
Published: October 2023

Abstract

Background
The coronavirus disease 2019 (COVID-19) cases continue to rise, and the demand for medical treatment and resources in healthcare systems surges. Assessing the viral shedding time (VST) of patients with COVID-19 can facilitate clinical decision making. Although some studies have been conducted on the factors affecting the VST of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), few prediction models are currently available.

Methods
This retrospective study included the consecutive patients with COVID-19 admitted to Xi’an Chest Hospital in Shaanxi, China, for treatment between December 19, 2021 and February 5, 2022. The clinical data of the patients were extracted from their electronic medical records. Combining significant factors affecting the VST, a nomogram was developed to predict the VST of the SARS-CoV-2 Delta variant in patients with COVID-19.

Results
We included 332 patients in this study. The average VST was 21 d. VST was significantly prolonged in patients with severe clinical symptoms, sore throat, old age, long time from onset to diagnosis, and an abnormal white blood cell count. Consequently, we developed a nomogram prediction model using these 5 variables. The concordance index (C-index) of this nomogram was 0.762, and after internal validation using bootstrapping (1000 resamples), the adjusted C-index was 0.762. The area under the nomogram’s receiver operator characteristic curve showed good discriminative ability (0.965). The calibration curve showed high consistency. The VST was prolonged in the group with lower model fitting scores according to the Kaplan-Meier curve (χ2=286, log-rank P < 0.001).

Conclusions
We developed a nomogram for predicting VST based on 5 easily accessible factors. It can effectively estimate the appropriate isolation period, control viral transmission, and optimize clinical strategies.