bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural analyses of the GI.4 norovirus by cryo-electron microscopy and X-ray crystallography revealing binding sites for human monoclonal antibodies
Authors: Kimura-Someya Tomomi , Katsura Kazushige , Kato-Murayama Miyuki , Hosaka Toshiaki , Uchikubo-Kamo Tomomi , Ihara Kentaro , Hanada Kazuharu , Sato Shin , Murayama Kazutaka , Kataoka Michiyo , Shirouzu Mikako , Someya Yuichi 
Published: April 2024

ABSTRACT

Noroviruses are major causative agents of acute nonbacterial gastroenteritis in humans. There are neither antiviral therapeutic agents nor vaccines for noroviruses at this time. To evaluate the potential usefulness of two previously isolated human monoclonal antibody fragments, CV-1A1 and CV-2F5, we first conducted a single-particle analysis to determine the cryo-electron microscopy structure of virus-like particles (VLPs) from the genogroup I genotype 4 (GI.4) Chiba strain uniformly coated with CV-1A1 fragments. The results revealed that the GI.4-specific CV-1A1 antibody bound to the P2 subdomain, in which amino acids are less conserved and variable. Interestingly, a part of the CV-1A1 intrudes into the histo-blood group antigen-binding site, suggesting that this antibody might exert neutralizing activity. Next, we determined the crystal structure of the protruding (P) domain of the capsid protein in the complex form with the CV-2F5 antibody fragment. Consistent with the cross-reactivity, the CV-2F5 bound to the P1 subdomain, which is rich in amino acids conserved among the GI strains, and moreover induced a disruption of Chiba VLPs. These results suggest that the broadly reactive CV-2F5 antibody can be used as both a universal detection reagent and an antiviral drug for GI noroviruses.

IMPORTANCE
We conducted the structural analyses of the VP1 protein from the GI.4 Chiba norovirus to identify the binding sites of the previously isolated human monoclonal antibodies CV-1A1 and CV-2F5. The cryo-electron microscopy of the Chiba virus-like particles (VLPs) complexed with the Fv-clasp forms of GI.4-specific CV-1A1 revealed that this antibody binds to the highly variable P2 subdomain, suggesting that this antibody may have neutralizing ability against the GI.4 strains. X-ray crystallography revealed that the CV-2F5 antibody bound to the P1 subdomain, which is rich in conserved amino acids. This result is consistent with the ability of the CV-2F5 antibody to react with a wide variety of GI norovirus strains. It is also found that the CV-2F5 antibody caused a disruption of VLPs. Our findings, together with previous reports on the structures of VP1 proteins and VLPs, are expected to open a path for the structure-based development of antivirals and vaccines against norovirus disease.
New opioid prescription claims and their clinical indications: results from health administrative data in Quebec, Canada, over 14 years
Authors: Attisso Eugene , Guenette Line , Dionne Clermont E , Kröger Edeltraut , Dialahy Isaora , Tessier Sebastien , Jean Sonia 
Published: April 2024

ObjectivesDescribe new opioid prescription claims, their clinical indications and annual trends among opioid naïve adults covered by the Quebec’s public drug insurance plan (QPDIP) for the fiscal years 2006/2007–2019/2020.Design and settingA retrospective observational study was conducted using data collected between 2006/2007 and 2019/2020 within the Quebec Integrated Chronic Disease Surveillance System, a linkage administrative data.ParticipantsA cohort of opioid naïve adults and new opioid users was created for each study year (median number=2 263 380 and 168 183, respectively, over study period).InterventionNo.Main outcome measure and analysesA new opioid prescription was defined as the first opioid prescription claimed by an opioid naïve adult during a given fiscal year. The annual incidence proportion for each year was then calculated and standardised for age. A hierarchical algorithm was built to identify the most likely clinical indication for this prescription. Descriptive and trend analyses were performed.ResultsThere was a 1.7% decrease of age-standardised annual incidence proportion during the study period, from 7.5% in 2006/2007 to 5.8% in 2019/2020. The decrease was highest after 2016/2017, reaching 5.5% annual percentage change. Median daily dose and days’ supply decreased from 27 to 25 morphine milligram equivalent/day and from 5 to 4 days between 2006/2007 and 2019/2020, respectively. Between 2006/2007 and 2019/2020, these prescriptions’ most likely clinical indications increased for cancer pain from 34% to 48%, for surgical pain from 31% to 36% and for dental pain from 9% to 11%. Inversely, the musculoskeletal pain decreased from 13% to 2%. There was good consistency between the clinical indications identified by the algorithm and prescriber’s specialty or user’s characteristics.ConclusionsNew opioid prescription claims (incidence, dose and days’ supply) decreased slightly over the last 14 years among QPDIP enrollees, especially after 2016/2017. Non-surgical and non-cancer pain became less common as their clinical indication.
Predicting pressure injury risk in hospitalised patients using machine learning with electronic health records: a US multilevel cohort study
Authors: Padula William V , Armstrong David G , Pronovost Peter J , Saria Suchi 
Published: April 2024

ObjectiveTo predict the risk of hospital-acquired pressure injury using machine learning compared with standard care.DesignWe obtained electronic health records (EHRs) to structure a multilevel cohort of hospitalised patients at risk for pressure injury and then calibrate a machine learning model to predict future pressure injury risk. Optimisation methods combined with multilevel logistic regression were used to develop a predictive algorithm of patient-specific shifts in risk over time. Machine learning methods were tested, including random forests, to identify predictive features for the algorithm. We reported the results of the regression approach as well as the area under the receiver operating characteristics (ROC) curve for predictive models.SettingHospitalised inpatients.ParticipantsEHRs of 35 001 hospitalisations over 5 years across 2 academic hospitals.Main outcome measureLongitudinal shifts in pressure injury risk.ResultsThe predictive algorithm with features generated by machine learning achieved significantly improved prediction of pressure injury risk (p<0.001) with an area under the ROC curve of 0.72; whereas standard care only achieved an area under the ROC curve of 0.52. At a specificity of 0.50, the predictive algorithm achieved a sensitivity of 0.75.ConclusionsThese data could help hospitals conserve resources within a critical period of patient vulnerability of hospital-acquired pressure injury which is not reimbursed by US Medicare; thus, conserving between 30 000 and 90 000 labour-hours per year in an average 500-bed hospital. Hospitals can use this predictive algorithm to initiate a quality improvement programme for pressure injury prevention and further customise the algorithm to patient-specific variation by facility.
Social media for palliative and end-of-life care research: a systematic review
Authors: Wang Yijun , Koffman Jonathan , Gao Wei , Zhou Yuxin , Chukwusa Emeka , Curcin Vasa 
Published: April 2024

BackgroundSocial media with real-time content and a wide-reaching user network opens up more possibilities for palliative and end-of-life care (PEoLC) researchers who have begun to embrace it as a complementary research tool. This review aims to identify the uses of social media in PEoLC studies and to examine the ethical considerations and data collection approaches raised by this research approach.MethodsNine online databases were searched for PEoLC research using social media published before December 2022. Thematic analysis and narrative synthesis approach were used to categorise social media applications.Results21 studies were included. 16 studies used social media to conduct secondary analysis and five studies used social media as a platform for information sharing. Ethical considerations relevant to social media studies varied while 15 studies discussed ethical considerations, only 6 studies obtained ethical approval and 5 studies confirmed participant consent. Among studies that used social media data, most of them manually collected social media data, and other studies relied on Twitter application programming interface or third-party analytical tools. A total of 1 520 329 posts, 325 videos and 33 articles related to PEoLC from 2008 to 2022 were collected and analysed.ConclusionsSocial media has emerged as a promising complementary research tool with demonstrated feasibility in various applications. However, we identified the absence of standardised ethical handling and data collection approaches which pose an ongoing challenge. We provided practical recommendations to bridge these pressing gaps for researchers wishing to use social media in future PEoLC-related studies.
Discontinuing semaglutide after weight loss: strategy for weight maintenance and a possible new side effect
Authors: Carris Nicholas W. , Wallace Shawn , DuCoin Christopher G. , Mhaskar Rahul , Stern Marilyn , Bunnell Brian 
Published: April 2024

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) facilitate weight loss. Weight regain off therapy is concerning. We reported the case of a 35-year-old male prescribed oral semaglutide with 22.7 kg weight loss over 120 days. Herein, we describe the clinical course when discontinuing GLP-1 RA therapy, one approach to maintaining weight loss after discontinuation, and a possible new side effect. At day 120, we continued oral semaglutide 7 mg daily, down from 14 mg, for weight maintenance with subsequent weight regain. We re-increased semaglutide to 14 mg/day with weight re-loss within 1 month and weight maintance for a year. We then discontinued semaglutide; weight loss was maintained for 6 months. The patient reported lactose intolerance ∼13 months before starting semaglutide. During semaglutide therapy, the patient reported worsened lactose intolerance and new gluten intolerance. Food allergy/celiac testing were negative. Intolerances did not improve with semaglutide discontinuation. Six months after semaglutide discontinuation, the patient was diagnosed with small intestinal bacterial overgrowth, possibly worsened by semaglutide. Factors potentially supporting weight maintenance were early drug treatment for new-onset obesity, non-geriatric age, strength training, and diet modification. The case highlights tailoring approaches to maintain weight loss without GLP-1 RAs. Trials are needed to optimize weight maintenance strategies.
Preclinical Efficacy of a PSMA-Targeted Actinium-225 Conjugate (225Ac-Macropa-Pelgifatamab): A Targeted Alpha Therapy for Prostate Cancer
Authors: Schatz Christoph A. , Zitzmann-Kolbe Sabine , Moen Ingrid , Klotz Monika , Nair Shankari , Stargard Stefan , Bjerke Roger M. , Wickstrøm Biseth Katrine , Feng Yuan Zeng , Indrevoll Bård , Cruciani Veronique , Karlsson Jenny , Haendler Bernard , Nielsen Carsten H. , Alfsen Maria Z. , Hammer Stefanie , Hennekes Hartwig , Cuthbertson Alan , Hagemann Urs B. , Larsen Åsmund 
Published: April 2024

Abstract

Purpose:
Initially, prostate cancer responds to hormone therapy, but eventually resistance develops. Beta emitter-based prostate-specific membrane antigen (PSMA)-targeted radionuclide therapy is approved for the treatment of metastatic castration-resistant prostate cancer. Here we introduce a targeted alpha therapy (TAT) consisting of the PSMA antibody pelgifatamab covalently linked to a macropa chelator and labeled with actinium-225 and compare its efficacy and tolerability with other TATs.

Experimental Design:
The in vitro characteristics and in vivo biodistribution, antitumor efficacy, and tolerability of 225Ac-macropa-pelgifatamab (225Ac-pelgi) and other TATs were investigated in cell line– and patient-derived prostate cancer xenograft models. The antitumor efficacy of 225Ac-pelgi was also investigated in combination with the androgen receptor inhibitor darolutamide.

Results:
Actinium-225-labeling of 225Ac-pelgi was efficient already at room temperature. Potent in vitro cytotoxicity was seen in PSMA-expressing (LNCaP, MDA-PCa-2b, and C4-2) but not in PSMA-negative (PC-3 and DU-145) cell lines. High tumor accumulation was seen for both 225Ac-pelgi and 225Ac-DOTA-pelgi in the MDA-PCa-2b xenograft model. In the C4-2 xenograft model, 225Ac-pelgi showed enhanced antitumor efficacy with a T/Cvolume (treatment/control) ratio of 0.10 compared with 225Ac-DOTA-pelgi, 225Ac-DOTA-J591, and 227Th-HOPO-pelgifatamab (227Th-pelgi; all at 300 kBq/kg) with T/Cvolume ratios of 0.37, 0.39, and 0.33, respectively. 225Ac-pelgi was less myelosuppressive than 227Th-pelgi. 225Ac-pelgi showed dose-dependent treatment efficacy in the patient-derived KuCaP-1 model and strong combination potential with darolutamide in both cell line– (22Rv1) and patient-derived (ST1273) xenograft models.

Conclusions:
These results provide a strong rationale to investigate 225Ac-pelgi in patients with prostate cancer. A clinical phase I study has been initiated (NCT06052306).
Cabeza de ofidio, ojos de reptil: a propósito de Paris-Austerlitz, de Rafael Chirbes
Authors: Valls Fernando 
Published: April 2024

El artículo discute la última novela del escritor valenciano Rafael Chirbes, Paris-Austerlitz. Se cuenta en esta novela el encuentro durante 1986, en un París sórdido, naturalista, entre un maduro obrero francés especializado y un joven español de familia acomodada aspirante a pintor. La desigual relación que mantienen, territorio propicio para la lucha de clases, transitará por la pasión, el interés, los celos y el desamor, aunque la aparición de la plaga, del mal, llevará a quien más se entrega, al menos pragmático de los dos, a la muerte”
Influence of Body Mass Index on Radiation Exposure Across Imaging Modalities in the Evaluation of Chest Pain
Authors: Sperry Brett W. , Vamenta Mary Stefanie , Gunta Satya Preetham , Thompson Randall C. , Einstein Andrew J. , Castillo Michelle , Chaudhary Priyanka D. , Bremner Luca I. , Cohen Yosef A. , Bateman Timothy M. , McGhie A. Iain 
Published: April 2024

Background
Essential to a patient‐centered approach to imaging individuals with chest pain is knowledge of differences in radiation effective dose across imaging modalities. Body mass index (BMI) is an important and underappreciated predictor of effective dose. This study evaluated the impact of BMI on estimated radiation exposure across imaging modalities.

Methods and Results

This was a retrospective analysis of patients with concern for cardiac ischemia undergoing positron emission tomography (PET)/computed tomography (CT), cadmium zinc telluride single‐photon emission CT (SPECT) myocardial perfusion imaging, or coronary CT angiography (CCTA) using state‐of‐the‐art imaging modalities and optimal radiation‐sparing protocols. Radiation exposure was calculated across BMI categories based on established cardiac imaging–specific conversion factors. Among 9046 patients (mean±SD age, 64.3±13.1 years; 55% men; mean±SD BMI, 30.6±6.9 kg/m
2
), 4787 were imaged with PET/CT, 3092 were imaged with SPECT/CT, and 1167 were imaged with CCTA. Median (interquartile range) radiation effective doses were 4.4 (3.9–4.9) mSv for PET/CT, 4.9 (4.0–6.3) mSv for SPECT/CT, and 6.9 (4.0–11.2) mSv for CCTA. Patients at a BMI <20 kg/m
2
had similar radiation effective dose with all 3 imaging modalities, whereas those with BMI ≥20 kg/m
2
had the lowest effective dose with PET/CT. Radiation effective dose and variability increased dramatically with CCTA as BMI increased, and was 10 times higher in patients with BMI >45 kg/m
2
compared with <20 kg/m
2
(median, 26.9 versus 2.6 mSv). After multivariable adjustment, PET/CT offered the lowest effective dose, followed by SPECT/CT, and then CCTA (
P
<0.001).

Conclusions
Although median radiation exposure is modest across state‐of‐the‐art PET/CT, SPECT/CT, and CCTA systems using optimal radiation‐sparing protocols, there are significant variations across modalities based on BMI. These data are important for making patient‐centered decisions for ischemic testing.
Origins
Authors: Tucker Aviezer 
Published: April 2024

Abstract
Scientific origins are information sources that transmit encoded information signals to receivers. Originary sciences identify information preserving receivers and decode the signals to infer their origins. Paradigmatic cases of scientific origination such as the Big Bang, the origins of species, horizontal gene transfer, the origin of the Polynesian potato, and ideational origins in the history of ideas are analyzed to discover what is common to them ontologically and epistemically. Some causes are not origins. Origination supervenes on causation, but has different properties. The unique properties of origins that causes do not share shield theories of origination from the kind of counterexamples and counterintuitive results that challenge comparable theories of causation. The epistemology of origination may serve as a basis for founding a novel epistemic and methodological division of the sciences into originary historical sciences and causal theoretical sciences.
Sperm development and structure in Bursaphelenchus luxuriosae (Nematoda: Aphelenchoidea: Aphelenchoididae)
Authors: Yushin Vladimir V. , Gliznutsa Lyubov A. , Kanzaki Natsumi , Ryss Alexander 
Published: April 2024

Summary
Sperm development and structure in the wood-inhabiting fungal and plant-feeding nematode, Bursaphelenchus luxuriosae, were studied using transmission electron microscopy to evaluate interspecific similarities and differences of spermatozoa in nematodes. In general, spermatogenesis in B. luxuriosae fits the ‘rhabditid’ pattern supported by morphological and phylogenetic analysis of the order Rhabditida. Spermatocyte development includes formation of complexes of fibrous bodies (FBs) with membranous organelles (MOs), the complexes dissociate in the spermatids into separate components, and the immature sperm contain MOs but lack FBs, which transform into a dense matrix of sperm cytoplasm. The female spermatheca contains mature spermatozoa as bipolar cells subdivided into a pseudopod devoid of organelles and a main cell body containing a nucleus without a nuclear envelope, numerous mitochondria, and peripheral MOs as pouches opening to the exterior via pores. Data on B. luxuriosae are used for analysis of variable quantitative and morphological characteristics of spermatozoa in Aphelenchoidea. General size of spermatozoa and their MOs have little value for comparative analysis. The MO knobbles look uniform in immature spermatozoa of each aphelenchoidid species studied and may be considered as a taxonomically specific ultrastructural feature. The presence or absence of FBs in immature spermatozoa demonstrates the diagnostic value of the aphelenchoidid sperm structure at the species level. Analysis also shows close similarity of spermatozoa in Bursaphelenchus spp. and Caenorhabditis elegans, the model species with comprehensive data on sperm biology. This may be used to identify new ways for the control and suppression of harmful nematode species such as B. xylophilus.
Scrutizing the Constructions of waʾd through Major Lexicographical Sources
Authors: Paraskeva Tsampika-Mika 
Published: April 2024

Abstract
The term waʾd is commonly understood to refer to the alleged custom of the pre-Islamic era to bury new-born girls alive after their birth. As such, it has become part and parcel of the portrayal of pre-Islamic Arabia (ǧāhiliyya). The present paper provides a thorough analysis of the concept of waʾd and its relevant cognates, as they occur in major lexicographical sources, aiming to shed light on certain mechanisms of construction of what is traditionally accepted as an accurate depiction of a real practice.
Nothochrysinae (Neuroptera: Chrysopidae) from the early Eocene Fur Formation, Denmark, with description of a new genus
Authors: MAKARKIN VLADIMIR N. , PERKOVSKY EVGENY E. 
Published: April 2024

Furochrysa alisae gen et sp. nov. is described, and Stephenbrooksia multifurcata Willmann, 1993 and Danochrysa madseni Willmann, 1993 are re-described based on their holotypes and additional specimens from the early Eocene Fur Formation of Denmark. The very long crossvein 1icu between CuA and CuP in the hind wing distinguishes Furochrysa gen. nov. from all other Nothochrysinae. The hind wing venation of the holotype of S. multifurcata is strongly aberrant; in particular, its MA is deeply forked proximad the origin of RP, while it is not forked proximad the pseudocubitus in other Chrysopidae. The forewing venation of the three examined specimens of D. madseni show variability in the branching of the anterior branch of CuP and A2. The chrysopid assemblage of the early Eocene Fur Formation strongly differs from that of the late Paleogene (late Eocene/Oligocene) of Europe, while the nothochrysines of the early and late Paleogene of North America do not especially differ.
Cost Savings of Whole Blood Versus Component Therapy at a Community Level 1 Trauma Center
Authors: Murphy Rachel C. , Johnson Tyler W. , Mack Thomas J. , Burke Rachel E. , Damiano Nicholas P. , Heger Laura , Minner Nicholas , German Emily , Wilson Angela , Mount Michael G. , Thurston Brian C. , Mentzer Caleb J. 
Published: April 2024

Background Blood product component-only resuscitation (CORe) has been the standard of practice in both military and civilian trauma care with a 1:1:1 ratio used in attempt to recreate whole blood (WB) until recent data demonstrated WB to confer a survival advantage, leading to the emergence of WB as the contemporary resuscitation strategy of choice. Little is known about the cost and waste reduction associated with WB vs CORe. Methods This study is a retrospective single-center review of adult trauma patients admitted to a community trauma center who received WB or CORe as part of their massive transfusion protocol (MTP) resuscitation from 2017 to 2021. The WB group received a minimum of one unit WB while CORe received no WB. Univariate and multivariate analyses were completed. Statistical analysis was conducted using a 95% confidence level. Non-normally distributed, continuous data were analyzed using the Wilcoxon rank sum test. Results 576 patients were included (201 in WB and 375 in CORe). Whole blood conveyed a survival benefit vs CORe (OR 1.49 P < .05, 1.02-2.17). Whole blood use resulted in an overall reduction in products prepared (25.8%), volumes transfused (16.5%), product waste (38.7%), and MTP activation (56.3%). Cost savings were $849 923 annually and $3 399 693 over the study period. Discussion Despite increased patient volumes over the study period (43.7%), the utilization of WB as compared to CORe resulted in an overall $3.39 million cost savings while improving mortality. As such, we propose WB should be utilized in all resuscitation strategies for the exsanguinating trauma patient.