bluuebunny/crossref_metadata_2025 huggingface dataset:
GGC repeat expansion in NOTCH2NLC induces dysfunction in ribosome biogenesis and translation
Authors: Fan Yu , Li Meng-jie , Yang Jing , Li Shuang-jie , Hao Xiao-yan , Li Jia-di , Wang Yun-chao , Tang Mi-bo , Zhang Chan , Shi Jing-jing , Ma Dong-rui , Guo Meng-nan , Liu Fen , Shen Si , Yao Da-bao , Zuo Chun-yan , Mao Cheng-yuan , Hu Zheng-wei , Zhang Shuo , Yang Zhi-hua , Guo Guang-yu , Yang Jing-hua , Xia Zong-ping , Xu Yu-ming , Shi Chang-he
Published: February 2023

GGC repeat expansion in the 5′ untranslated region (UTR) of NOTCH2NLC is associated with a broad spectrum of neurological disorders, especially neuronal intranuclear inclusion disease (NIID). Studies have found that GGC repeat expansion in NOTCH2NLC induces the formation of polyglycine (polyG)-containing protein, which is involved in the formation of neuronal intranuclear inclusions. However, the mechanism of neurotoxicity induced by NOTCH2NLC GGC repeats is unclear.

Here, we used NIID patient-specific induced pluripotent stem cell (iPSC)-derived 3D cerebral organoids (3DCOs) and cellular models to investigate the pathophysiological mechanisms of NOTCH2NLC GGC repeat expansion.

IPSC-derived 3DCOs and cellular models showed the deposition of polyG-containing intranuclear inclusions. The NOTCH2NLC GGC repeats could induce the upregulation of autophagic flux, enhance integrated stress response and activate EIF2α phosphorylation. Bulk RNA sequencing for iPSC-derived neurons and single-cell RNA sequencing (scRNA-seq) for iPSC-derived 3DCOs revealed that NOTCH2NLC GGC repeats may be associated with dysfunctions in ribosome biogenesis and translation. Moreover, NOTCH2NLC GGC repeats could induce the NPM1 nucleoplasm translocation, increase nucleolar stress, impair ribosome biogenesis and induce ribosomal RNA sequestration, suggesting dysfunction of membraneless organelles in the NIID cellular model. Dysfunctions in ribosome biogenesis and phosphorylated EIF2α and the resulting increase in the formation of G3BP1-positive stress granules may together lead to whole-cell translational inhibition, which may eventually cause cell death. Interestingly, scRNA-seq revealed that NOTCH2NLC GGC repeats may be associated with a significantly decreased proportion of immature neurons while 3DCOs were developing.

Together, our results underscore the value of patient-specific iPSC-derived 3DCOs in investigating the mechanisms of polyG diseases, especially those caused by repeats in human-specific genes.
Determination of Carnosic Acid by a Novel HPLC-UV Method in Human Plasma and Application to a Prototype Pharmacokinetic Study
Authors: Ceylan Burhan , Tırıs Gizem , Tekkeli Evrim Kepekci
Published: February 2023

An HPLC method with UV detection was developed for the determination of carnosic acid in human plasma and applied to a pharmacokinetic study after oral administration of Rosemary extract to a healthy volunteer. Sample preparation depends on liquid–liquid extraction with hexane. Chromatographic separation was achieved with C18 column (150 mm × 4.6 mm × 5 μm), at 25°C with isocratic elution, mobile phase composed of solution A (methanol), and solution B (2% o-phosphoric acid in water) (90:10, v/v) at flow rate of 1.0 mL/min. The analyte was detected at 230 nm. The retention time is 4.20 ± 0.03 min. The method was validated in terms of accuracy, precision, specificity, robustness and detection and quantification limits, in accordance with European Medicines Agency guidelines. LOD and LOQ were found to be 0.075 and 0.25 ng/mL, respectively. The method was applied to the analysis of carnosic acid in human plasma with good recovery as 91.7%. The plasma concentration-time profile and pharmacokinetic parameters: AUC0–t, AUC0–∞, Cmax, tmax, t1/2 were calculated according to the assays. The method can certainly be used for routine analysis of carnosic acid in human plasma after oral administration of Rosemary extract, and for phase I clinical studies and bioavailability-bioequivalance studies as well.
Changes in Body Mass Index with Longer-term Integrase Inhibitor Use: A Longitudinal Analysis of Data from the Randomized Trial to Prevent Vascular Events in Human Immunodeficiency Virus (REPRIEVE)
Authors: Kileel Emma M , Malvestutto Carlos D , Lo Janet , Fitch Kathleen V , Fichtenbaum Carl J , Aberg Judith A , Zanni Markella V , Martinez Esteban , Okeke Nwora Lance , Kumar Princy , Joao Esau , Bares Sara H , Berrner Daniel , Smieja Marek , Roa Jhoanna C , McCallum Sara , Douglas Pamela S , Ribaudo Heather J , Grinspoon Steven K
Published: February 2023

Over 2-years of follow-up, integrase strand transfer inhibitor (INSTI)-use was associated with weight gain among those on an INSTI <2 years at entry (+0.27 kg/m2/year; 95% confidence interval [CI], .22 to .33 vs +0.17 kg/m2/year; 95% CI, .12 to .23; P = .01), but not those on an entry INSTI >2 years.
Primary cardiac mesothelioma presenting with fulminant recurrent pericarditis: a case report
Authors: Schwartzenberg Shmuel , Shapira Yaron , Rubachevski Victor , Sharony Ram
Published: February 2023

Background

Primary pericardial mesothelioma is an extremely rare disease. Prognosis is poor, with little effects of chemo- or radio-therapy. The majority of cases is diagnosed at autopsy.

Case summary

A 22-year-old man, who presented with recurrent pericarditis and large pericardial effusion 2 months after a second BNT162b2 COVID-19 vaccine, underwent pericardiocentesis and pericardial window. Pathology specimen of pericardium revealed benign mesothelial inflammation, consistent with acute pericarditis. Four months later, he presented with a large pericardial mass manifesting in heart failure and underwent urgent pericardiectomy. A new pathology specimen immunostaining and fluorescence in situ hybridization analysis revealed pericardial mesothelioma. Despite intensive care, the patient died 3 weeks later.

Discussion

Primary pericardial mesothelial should be considered in the differential diagnosis of refractory recurrent pericarditis, even with prior biopsy-proven pericarditis or when a putative trigger (COVID-19 mRNA prior vaccination) is suspected, as was the case in this patient. Tumour diagnosis and identification consist of multimodal imaging and laboratory tests. A multidisciplinary, individualized care approach should be performed.
Postoperative ST-segment elevation caused by mechanical compression of the native right coronary artery by a pericardial drainage tube
Authors: Escherich Teresa , Mogilansky Christian , Massoudy Parwis
Published: February 2023

ST-segment elevation is often the first remarkable sign of postoperative cardiac ischaemia. It requires prompt diagnostic measures and an early treatment to improve the patient’s outcome. We describe a case of early postoperative ST-segment elevation due to mechanical compression of the native right coronary artery by a pericardial drainage tube in a patient after replacement of the ascending aorta.
Promotion of healthy nutrition in primary and secondary cardiovascular disease prevention: a clinical consensus statement from the European Association of Preventive Cardiology
Authors: Vassiliou Vassilios S , Tsampasian Vasiliki , Abreu Ana , Kurpas Donata , Cavarretta Elena , O’Flaherty Martin , Colombet Zoé , Siegrist Monika , De Smedt Delphine , Marques-Vidal Pedro
Published: February 2023

Background

Poor dietary habits are common and lead to significant morbidity and mortality. However, addressing and improving nutrition in various cardiovascular settings remain sub-optimal. This paper discusses practical approaches to how nutritional counselling and promotion could be undertaken in primary care, cardiac rehabilitation, sports medicine, paediatric cardiology, and public health.

Discussion

Nutrition assessment in primary care could improve dietary patterns and use of e-technology is likely to revolutionize this. However, despite technological improvements, the use of smartphone apps to assist with healthier nutrition remains to be thoroughly evaluated. Cardiac rehabilitation programmes should provide individual nutritional plans adapted to the clinical characteristics of the patients and include their families in the dietary management. Nutrition for athletes depends on the sport and the individual and preference should be given to healthy foods, rather than nutritional supplements. Nutritional counselling is also very important in the management of children with familial hypercholesterolaemia and congenital heart disease. Finally, policies taxing unhealthy foods and promoting healthy eating at the population or workplace level could be effective for prevention of cardiovascular diseases. Within each setting, gaps in knowledge are provided.

Conclusion

This clinical consensus statement contextualizes the clinician’s role in nutrition management in primary care, cardiac rehabilitation, sports medicine, and public health, providing practical examples of how this could be achieved.
Diagnostic delay in arrhythmogenic cardiomyopathy
Authors: Tini Giacomo , Graziosi Maddalena , Musumeci Beatrice , Targetti Mattia , Russo Domitilla , Parisi Vanda , Argirò Alessia , Ditaranto Raffaello , Leone Ornella , Autore Camillo , Olivotto Iacopo , Biagini Elena
Published: February 2023

Aims

Diagnosis of arrhythmogenic cardiomyopathy (ACM) may be challenging, as it comprises diverse phenotypes (right dominant, biventricular, and left dominant), and each may overlap with other clinical entities. The issue of differential diagnosis with conditions mimicking ACM has been previously highlighted; however, a systematic analysis of ACM diagnostic delay, and of its clinical implications, is lacking.

Methods and results

Data of all ACM patients from three Italian Cardiomyopathy Referral Centres were reviewed to assess the time from first medical contact to definitive ACM diagnosis; a significant diagnostic delay was defined as a time to ACM diagnosis ≥2 years. Baseline characteristics and clinical course of patients with and without diagnostic delay were compared. Of 174 ACM patients, 31% experienced diagnostic delay, with a median time to diagnosis of 8 years (20% in right-dominant ACM, 33% in left-dominant ACM, and 39% in biventricular). Patients with diagnostic delay, when compared with those without, more frequently exhibited an ACM phenotype with left ventricular (LV) involvement (74 vs. 57%, P = 0.04) and a specific genetic background (none had plakophilin-2 variants). The most common initial (mis)diagnoses were dilated cardiomyopathy (51%), myocarditis (21%), and idiopathic ventricular arrhythmia (9%). At follow-up, all-cause mortality was greater in those with diagnostic delay (P = 0.03).

Conclusion

Diagnostic delay is common in patients with ACM, particularly in the presence of LV involvement, and is associated with greater mortality at follow-up. Clinical suspicion and increasing use of tissue characterization by cardiac magnetic resonance in specific clinical settings are of key importance for the timely identification of ACM.
Routine versus selective near-infrared spectroscopy-guided shunting during carotid eversion endarterectomy
Authors: Kondov Stoyan , Bothe Dominique , Beyersdorf Friedhelm , Czerny Martin , Harloff Andreas , Pooth Jan-Steffen , Kaier Klaus , Schöllhorn Joachim , Kreibich Maximilian , Siepe Matthias , Rylski Bartosz
Published: February 2023

OBJECTIVES

The aim of this study was to compare outcomes of routine shunting to near-infrared spectroscopy (NIRS)-guided shunting in patients undergoing eversion endarterectomy (EEA) under general anaesthesia.

METHODS

We retrospectively evaluated data of all patients undergoing EEA of the internal carotid artery (ICA) in our department from January 2011 until January 2019. Included were patients with EEA of the ICA and the patients were divided into 2 groups: selective-shunting group and routine-shunting group. Patients (i) with patch angioplasty during the surgery, (ii) undergoing surgery for restenosis and (ii) stenosis after radiation therapy, (iii) without recorded regional cerebral oxygen saturation trends, (iv) presenting with an emergency treatment indication and (v) operated upon by residents were excluded. In all patients, EEA was performed in general anaesthesia and under NIRS monitoring. One-to-one propensity score matching was used to compare EEA outcomes after routine shunting to NIRS-guided shunting. Primary end points were defined as perioperative stroke and in-hospital mortality after EEA.

RESULTS

Routine and NIRS-guided selective shunting were applied in 340 (34.0%) and 661 (66.0%) patients, respectively. A total of 277 pairs were generated via propensity score matching. Fifty-eight (20.1%) from the selective-shunting group were intraoperatively shunted. Concomitant procedures were more frequently performed in the routine-shunting group [170 (61.4%) vs 47 (17.0%), 180 (65%) vs 101 (36.5%), and 60 (21.7%) vs 6 (2.2%), P < 0.001]. The perioperative stroke rate in the routine-shunting group was higher as well [11 (4.0%) vs 3 (1.1%), P = 0.022]. In-hospital death was overall 0.2% (n = 1). Multivariable logistic regression in the matched patient indicated age (odds ratio 1.050, 95% confidence interval 1.002–1.104, P = 0.046) and routine shunting (odds ratio 2.788, confidence interval 1.119–7.428, P = 0.032) as risk factors for perioperative stroke during EEA of the ICA.

CONCLUSIONS

We found that, during EEA of the ICA, under general anaesthesia, NIRS-guided selective shunting was associated with a lower incidence of perioperative stroke than routine shunting.
One Concept, Many Worlds: Teaching toward the Future in an Imperfect Discipline
Authors: Mitzen Jennifer
Published: February 2023

An earlier version of this Research Note was presented as the Keynote Address at the ISA Northeast Conference November 2022. The conference theme was “Imagining World Futures: Exploring Alternative Visions of International Studies and World Politics in the Next 20–200 Years.”
Cost-effectiveness of point-of-care interventions to tackle inappropriate prescribing of antibiotics in high- and middle-income countries: a systematic review
Authors: D’hulster Erinn , De Burghgraeve Tine , Luyten Jeroen , Verbakel Jan Y
Published: February 2023

Background

Antimicrobial resistance (AMR) is propagated by widespread inappropriate use of antibiotics. In response, point-of-care interventions (POCIs) have been developed in primary care to preserve antibiotic effectiveness. Many of these POCIs are adopted based on their clinical value. However, assessment of their cost-effectiveness is crucial as well.

Objectives

To summarize the evidence on cost-effectiveness of POCIs aimed at tackling inappropriate antibiotic prescriptions in primary care in middle- and high-income countries. We also evaluate the quality of the evidence with particular attention to how these economic evaluations faced the challenge of capturing the impact of these POCIs on AMR.

Methods

Six scientific databases (MEDLINE, Embase, Web of Science, NHS EED, NHS HTA, the Cochrane Library) were searched for eligible articles published from 1999 to 2022. Their quality was appraised by means of the Drummond and CHEERS checklist.

Results

Twenty-nine articles met the selection criteria. Using their own (implicit) definitions of cost-effectiveness, evidence reported that point-of-care testing, scoring tools, electronic interventions, communication training, and multidimensional and educational interventions are more cost-effective than standard care. In contrast, studies found dipstick testing and audit-and-feedback interventions to be not cost-effective. Data synthesis took a narrative approach as eligible studies were not similar and/or reliable enough to pool their results through meta-analysis.

Conclusions

More high-quality evidence is needed to attain a thorough understanding of the cost-effectiveness of POCIs. Heterogeneity in terms of interventions and efficiency measures complicates comparing and generalizing results. Methodological recommendations are urgently needed to economically evaluate POCIs, focusing on how AMR should be accounted for.
Bacillus species: factories of plant protective volatile organic compounds
Authors: Poulaki Eirini G , Tjamos Sotiris E
Published: February 2023

Several studies have described the potential use of volatile organic compounds (VOCs) emitted by soil microorganisms, specifically of the genus Bacillus, as a sustainable solution for disease management in plants. The Bacillus species have been extensively studied as biocontrol agents (BCAs) due to their ability to inhibit pathogens, trigger induced systemic resistance (ISR) in plants, and enhance plant growth. The ability of the Bacillus species to produce long-lasting resting structures, such as endospores, makes them particularly appealing as BCAs. In recent years, there has been a growing body of research on the effects of Bacillus-emitted VOCs on plant pathogen growth and the triggering of ISR. This review aims to highlight recent advances in the understanding of the biological activities of Bacillus-emitted VOCs, identify new subjects for VOCs research, and stimulate interest in the academic and agri-business sectors for developing pre- and post-harvest application methods.
A framework to identify ethical concerns with ML-guided care workflows: a case study of mortality prediction to guide advance care planning
Authors: Cagliero Diana , Deuitch Natalie , Shah Nigam , Feudtner Chris , Char Danton
Published: February 2023

Objective

Identifying ethical concerns with ML applications to healthcare (ML-HCA) before problems arise is now a stated goal of ML design oversight groups and regulatory agencies. Lack of accepted standard methodology for ethical analysis, however, presents challenges. In this case study, we evaluate use of a stakeholder “values-collision” approach to identify consequential ethical challenges associated with an ML-HCA for advanced care planning (ACP). Identification of ethical challenges could guide revision and improvement of the ML-HCA.

Materials and Methods

We conducted semistructured interviews of the designers, clinician-users, affiliated administrators, and patients, and inductive qualitative analysis of transcribed interviews using modified grounded theory.

Results

Seventeen stakeholders were interviewed. Five “values-collisions”—where stakeholders disagreed about decisions with ethical implications—were identified: (1) end-of-life workflow and how model output is introduced; (2) which stakeholders receive predictions; (3) benefit-harm trade-offs; (4) whether the ML design team has a fiduciary relationship to patients and clinicians; and, (5) how and if to protect early deployment research from external pressures, like news scrutiny, before research is completed.

Discussion

From these findings, the ML design team prioritized: (1) alternative workflow implementation strategies; (2) clarification that prediction was only evaluated for ACP need, not other mortality-related ends; and (3) shielding research from scrutiny until endpoint driven studies were completed.

Conclusion

In this case study, our ethical analysis of this ML-HCA for ACP was able to identify multiple sites of intrastakeholder disagreement that mark areas of ethical and value tension. These findings provided a useful initial ethical screening.
Preanalytical Factors Influencing the Stability of Ethanol in Antemortem Blood and Urine Samples
Authors: Olds Maria L , Kosecki Patrick A , Jones Alan W
Published: February 2023

The quantitative analysis of ethanol in blood and other biological specimens is a commonly requested service from forensic science and toxicology laboratories worldwide. The measured blood alcohol concentration (BAC) constitutes important evidence when alcohol-related crimes are investigated, such as drunken driving or drug-related sexual assault. This review article considers the importance of various preanalytical factors that might influence changes in the ethanol concentration in blood after collection and before analysis or reanalysis after various periods of storage. When blood samples were collected by venipuncture from living subjects in evacuated tubes containing sodium fluoride (NaF) preservative, there was no evidence that the BAC increased after collection. Most studies found that the BAC decreased after collection depending on storage conditions, such as time and temperature, and the amount of NaF preservative. After the storage of blood specimens in a refrigerator (4oC) for up to 1–4 weeks, the changes in the BAC were not analytically significant. After storage for up to 12 months at 4oC, under the same conditions, the BAC decreased on average by 0.01–0.02 g%. The loss of ethanol does not appear to depend on the type of evacuated tubes used (glass or plastic), nominal volume (5 mL or 10 mL) or the amount of NaF preservative. Urine alcohol concentrations were also stable after various periods of storage, although in cases of glycosuria and urinary tract and/or Candida infections, the addition of NaF (1% w/v) was essential to prevent post-sampling synthesis of ethanol.
Mutant NPM1 maintains RASGRP3 protein stability via interaction with MID1 to promote acute myeloid leukemia cell proliferation and autophagy
Authors: Wang Youping , Pan Chi , Zhang Xia , Zhao Aiqi , Dong Ying
Published: February 2023

Acute myeloid leukemia is a heterogeneous hematologic malignancy with high mortality in the world. NPM1 gene mutations are a frequent occurrence in acute myeloid leukemia, leading to abnormal autophagy, while the mechanism of NPM1 mutation-driven acute myeloid leukemia pathogenesis remains to be fully elucidated. GEO microarrays were used to screen for dysregulated autophagy-related genes in NPM1-mutant acute myeloid leukemia and analysis of RASGRP3 expression and prognosis. Next, we explored the potential molecular mechanisms relationship between RASGRP3 and NPM1 through utilizing immunoprecipitation, Western blot, and cycloheximide assay. Further, CCK8, EdU staining, immunofluorescence, and Western blot were performed to explore the effect of RASGRP3 on cell proliferation and apoptosis in NPM1-mutated acute myeloid leukemia. Finally, Western blot was used to study the mechanism of action of RASGRP3. RASGRP3 expression was upregulated in NPM1-mutated acute myeloid leukemia. Mislocalized NPM1-mA in the cytoplasm could bind to E3 ubiquitin-protein ligase MID1 to block degradation of the RASGRP3 protein. RASGRP3 could also activate the EGFR-STAT3 axis to promote proliferation and autophagy in acute myeloid leukemia. In conclusion, our results identified RASGRP3 as a proto-oncogene in NPM1-mutated acute myeloid leukemia. The RASGRP3-EGFR/STAT3 axis may be a promising therapeutic target for this unique leukemic subtype.
Using a novel CLEM system to localize lipid droplets and membranes in desiccated embryonic axis cells of soybean seeds
Authors: Khanam Salma , Funatsu Takayuki , Tanaka Koji , Kaneko Yasuko
Published: February 2023

Lipid droplets and membranes in radicle cells from desiccated embryonic axes of soybean (Glycine max) seeds were examined by a recently developed correlative light and electron microscopy system, which has been designed to facilitate the observation of identical locations using an upright reflected light microscope and compact SEM successively with minimum time lapse. Lipids are major components of membranes and are also stored in numerous lipid droplets lining plasma membranes in many seed cells. Fluorescently stained lipid droplets and membranes in the desiccated radicle cells were mainly located along the surface of shrunk protoplasm and around presumptive protein bodies, which will turn into vacuoles and increase their volume for radicle protrusion. Co-localization of lipid droplets and membranes suggests the presence of a membrane protection mechanism during desiccation and rehydration processes that ensures prompt elongation of radicle cells during germination.
Pharmaco-endoscopic therapy for weight regain post-gastric bypass: a case report
Authors: Jarrah Mohammad , Mokadem Mohamad
Published: February 2023

About 1 in every 4 patients who undergo bariatric surgery regains significant amount of weight some time along their journey, posing it as a serious problem that needs to be addressed in a pandemic of obesity. Lifestyle modification, anti-obesity medications, and bariatric endoscopy are multiple therapeutic options that can be used to support any weight loss attempt. A 53-year-old woman with morbid obesity who responded adequately to gastric-bypass regained significant weight 8 years later. We initially approached her post-operative weight regain in a behavioral, pharmacologic non-invasive manner; however, she failed to appropriately respond to several anti-obesity medications. Upper endoscopy revealed a dilated gastric pouch and gastro-jejunal anastomosis (GJA) that was reduced using argon plasma coagulation (APC), but also with a modest response. We then added liraglutide to her APC endo-therapy sessions and subsequentially patient started losing significantly more weight. For selective post-bariatric surgery weight re-gainers, endoscopic and pharmaco-therapy combined may be needed for more effective results.
Equipping the Offline Population with Internet Access in an Online Panel: Does It Make a Difference?
Authors: Bach Ruben L , Cornesse Carina , Daikeler Jessica
Published: February 2023

Online panel surveys are often criticized for their inability to cover the offline population, potentially resulting in coverage error. Previous research has demonstrated that non-internet users in fact differ from online individuals on several sociodemographic characteristics. In attempts to reduce coverage error due to missing the offline population, several probability-based online panels equip offline households with an internet connection and a simple computer or tablet. However, the question remains whether the recruitment of offline individuals for an online panel leads to substantial changes in survey estimates. That is, it is unclear whether estimates derived from the survey data are affected by the differences between the groups of online and offline individuals. Against this background, we investigate how the inclusion of the previously offline population into the German Internet Panel affects various survey estimates such as voting behavior and social engagement. Overall, we find little evidence for the claim that equipping otherwise offline individuals with online access affects the estimates derived from previously online individuals only.
The Thousand-Pulsar-Array programme on MeerKAT – VIII. The subpulse modulation of 1198 pulsars
Authors: Song X , Weltevrede P , Szary A , Wright G , Keith M J , Basu A , Johnston S , Karastergiou A , Main R A , Oswald L S , Parthasarathy A , Posselt B , Bailes M , Buchner S , Hugo B , Serylak M
Published: February 2023

We report on the subpulse modulation properties of 1198 pulsars using the Thousand-Pulsar-Array programme on MeerKAT. About 35 per cent of the analysed pulsars exhibit drifting subpulses that are more pronounced towards the death line, consistent with previous studies. We estimate that this common phenomenon is detectable in 60 per cent of the overall pulsar population if high-quality data were available for all. This large study reveals the evolution of drifting subpulses across the pulsar population in unprecedented detail. In particular, we find that the modulation period P3 follows a V-shaped evolution with respect to the characteristic age τc, such that the smallest P3 values, corresponding to the Nyquist period P3 ≃ 2, are found at τc ≃ 107.5 yr. The V-shaped evolution can be interpreted and reproduced if young pulsars possess aliased fast intrinsic P3, which monotonically increase, ultimately achieving a slow unaliased P3. Enhancement of irregularities in intrinsic subpulse modulation by aliasing in small-τc pulsars would explain their observed less well defined P3’s and weaker spectral features. Modelling these results as rotating subbeams, their circulation must slow down as the pulsar evolves. This is the opposite to that expected if circulation is driven by $\boldsymbol{E}\times \boldsymbol{B}$ drift. This can be resolved if the observed P3 periodicity is due to a beat between an $\boldsymbol{E}\times \boldsymbol{B}$ system and the pulsar period. As a by-product, we identified the correct periods and spin-down rates for 12 pulsars, for which harmonically related values were reported in the literature.
ALMA confirmation of an obscured hyperluminous radio-loud AGN at z = 6.853 associated with a dusty starburst in the 1.5 deg2 COSMOS field
Authors: Endsley Ryan , Stark Daniel P , Lyu Jianwei , Wang Feige , Yang Jinyi , Fan Xiaohui , Smit Renske , Bouwens Rychard , Hainline Kevin , Schouws Sander
Published: February 2023

We present band 6 ALMA observations of a heavily obscured radio-loud (L1.4 GHz = 1025.4 W Hz−1) active galactic nucleus (AGN) candidate at zphot = 6.83 ± 0.06 found in the 1.5 deg2 COSMOS field. The ALMA data reveal detections of exceptionally strong [C ii]158 $\mu$m (z[C ii] = 6.8532) and underlying dust continuum emission from this object (COS-87259), where the [C ii] line luminosity, line width, and 158 $\mu$m continuum luminosity are comparable to those seen from z ∼ 7 sub-mm galaxies and quasar hosts. The 158 $\mu$m continuum detection suggests a total infrared luminosity of $9\times 10^{12}\, \mathrm{ L}_\odot$ with corresponding very large obscured star formation rate (1300 M⊙ yr−1) and dust mass ($2\times 10^9\, \mathrm{ M}_\odot$). The strong break seen between the VIRCam and IRAC photometry perhaps suggests that COS-87259 is an extremely massive reionization-era galaxy with $M_\ast \approx 1.7\times 10^{11}\, \mathrm{ M}_\odot$. Moreover, the MIPS, PACS, and SPIRE detections imply that this object harbours an AGN that is heavily obscured ($\tau _{_{\mathrm{9.7\,\mu m}}}=2.3$) with a bolometric luminosity of approximately $5\times 10^{13}\, \mathrm{ L}_\odot$. Such a very high AGN luminosity suggests that this object is powered by an ≈1.6 × 10$^9\, \mathrm{ M}_\odot$ black hole if accreting near the Eddington limit, and is effectively a highly obscured version of an extremely ultraviolet (UV)-luminous (M1450 ≈ −27.3) z ∼ 7 quasar. Notably, these z ∼ 7 quasars are an exceedingly rare population (∼0.001 deg−2), while COS-87259 was identified over a relatively small field. Future very wide area surveys with e.g. Roman and Euclid have the potential to identify many more extremely red yet UV-bright z ≳ 7 objects similar to COS-87259, providing richer insight into the occurrence of intense obscured star formation and supermassive black hole growth among this population.
The Concentration–Mass relation of massive, dynamically relaxed galaxy clusters: agreement between observations and ΛCDM simulations
Authors: Darragh-Ford Elise , Mantz Adam B , Rasia Elena , Allen Steven W , Morris R Glenn , Foster Jack , Schmidt Robert W , Wenrich Guillermo
Published: February 2023

The relationship linking a galaxy cluster’s total mass with the concentration of its mass profile and its redshift is a fundamental prediction of the Cold Dark Matter (CDM) paradigm of cosmic structure formation. However, confronting those predictions with observations is complicated by the fact that simulated clusters are not representative of observed samples where detailed mass profile constraints are possible. In this work, we calculate the symmetry-peakiness-alignment (SPA) morphology metrics for maps of X-ray emissivity from the three hundred project hydrodynamical simulations of galaxy clusters at four redshifts, and thereby select a sample of morphologically relaxed, simulated clusters, using observational criteria. These clusters have on average earlier formation times than the full sample, confirming that they are both morphologically and dynamically more relaxed than typical. We constrain the concentration–mass–redshift relation of both the relaxed and complete sample of simulated clusters, assuming power-law dependences on mass (κm) and 1 + z (κζ), finding κm = −0.12 ± 0.07 and κζ = −0.27 ± 0.19 for the relaxed subsample. From an equivalently selected sample of massive, relaxed clusters observed with Chandra, we find κm = −0.12 ± 0.08 and κζ = −0.48 ± 0.19, in good agreement with the simulation predictions. The simulated and observed samples also agree well on the average concentration at a pivot mass and redshift providing further validation of the ΛCDM paradigm in the properties of the largest gravitationally collapsed structures observed. This also represents the first clear detection of decreasing concentration with redshift, a longstanding prediction of simulations in data.
The growth of brightest cluster galaxies in the TNG300 simulation: dissecting the contributions from mergers andin situstar formation
Authors: Montenegro-Taborda Daniel , Rodriguez-Gomez Vicente , Pillepich Annalisa , Avila-Reese Vladimir , Sales Laura V , Rodríguez-Puebla Aldo , Hernquist Lars
Published: February 2023

We investigate the formation of brightest cluster galaxies (BCGs) in the TNG300 cosmological simulation of the IllustrisTNG project. Our cluster sample consists of 700 haloes with $M_{\rm 200}\ge 5 \times 10^{13} \, {\rm M}_{\odot }$ at z = 0, along with their progenitors at earlier epochs. This includes 280 systems with $M_{\rm 200}\ge 10^{14} \, {\rm M}_{\odot }$ at z = 0, as well as three haloes with $M_{\rm 200}\ge 10^{15} \, {\rm M}_{\odot }$. We find that the stellar masses and star formation rates of our simulated BCGs are in good agreement with observations at z ≲ 0.4, and that they have experienced, on average, ∼2 (∼3) major mergers since z = 1 (z = 2). Separating the BCG from the intracluster light (ICL) by means of a fixed 30 kpc aperture, we find that the fraction of stellar mass contributed by ex situ (i.e. accreted) stars at z = 0 is approximately 70, 80, and 90 per cent for the BCG, BCG + ICL, and ICL, respectively. Tracking our simulated BCGs back in time using the merger trees, we find that they became dominated by ex situ stars at z ∼1–2, and that half of the stars that are part of the BCG at z = 0 formed early (z ∼ 3) in other galaxies, but ‘assembled’ onto the BCG until later times (z ≈ 0.8 for the whole sample, z ≈ 0.5 for BCGs in $M_{\rm 200}\ge 5 \times 10^{14} \, {\rm M}_{\odot }$ haloes). Finally, we show that the stellar mass profiles of BCGs are often dominated by ex situ stars at all radii, with stars from major mergers being found closer to the centre, while stars that were tidally stripped from other galaxies dominate the outer regions.
Transgenerational Social Structures and Fictional Actors: Community-Based Responsibility for Future Generations
Authors: Andina Tiziana , Corvino Fausto
Published: February 2023

The notion of transgenerational community is usually based on two diachronic interactions. The first interaction consists of present generations taking up the legacy (not only economic, but also institutional, artistic, cultural, and so forth) of past generations and giving it continuity, exercising a form of active agency. The second interaction occurs when present generations pass on their legacy to future generations. This is supposed to expand the boundaries of the community in a transgenerational sense (both backward- and forward-looking). In this article we argue that the transgenerational community can be grounded on a different ontological insight: future generations play the role of fictional actors for present generations, i.e., present generations entertain a present-time interaction with future generations, insofar as future generations are functional for the realization of transgenerational actions. This lays the foundations for more solid community-based bonds of intergenerational justice.
Global variations in critical drought thresholds that impact vegetation
Authors: Li Xiangyi , Piao Shilong , Huntingford Chris , Peñuelas Josep , Yang Hui , Xu Hao , Chen Anping , Friedlingstein Pierre , Keenan Trevor F , Sitch Stephen , Wang Xuhui , Zscheischler Jakob , Mahecha Miguel D
Published: February 2023

Identifying the thresholds of drought that, if crossed, suppress vegetation functioning is vital for accurate quantification of how land ecosystems respond to climate variability and change. We present a globally applicable framework to identify drought thresholds for vegetation responses to different levels of known soil-moisture deficits using four remotely sensed vegetation proxies spanning 2001–2018. The thresholds identified represent critical inflection points for changing vegetation responses from highly resistant to highly vulnerable in response to drought stress, and as a warning signal for substantial vegetation impacts. Drought thresholds varied geographically, with much lower percentiles of soil-moisture anomalies in vegetated areas covered by more forests, corresponding to a comparably stronger capacity to mitigate soil water deficit stress in forested ecosystems. Generally, those lower thresholds are detected in more humid climates. State-of-the-art land models, however, overestimated thresholds of soil moisture (i.e. overestimating drought impacts), especially in more humid areas with higher forest covers and arid areas with few forest covers. Based on climate model projections, we predict that the risk of vegetation damage will increase by the end of the twenty-first century in some hotspots like East Asia, Europe, Amazon, southern Australia and eastern and southern Africa. Our data-based results will inform projections on future drought impacts on terrestrial ecosystems and provide an effective tool for drought management.
Hospitalizations for Unspecified Mycoses in a Large Administrative Data Set and Implications for Fungal Disease Burden Estimates, United States, 2019–2021
Authors: Benedict Kaitlin , Baggs James , Wolford Hannah , Jackson Brendan R , Gold Jeremy A W
Published: February 2023

Fungal diseases are frequently coded as “unspecified mycoses” in data sets used to estimate disease burden. In a large administrative database, 50.9% of unspecified mycosis hospitalizations during 2019–2021 had positive fungal laboratory testing, most commonly Candida (79.1%), highlighting a potential need for improved coding practices and greater fungal laboratory testing.
Investigator-Determined Categories for Fever of Unknown Origin (FUO) Compared With International Classification of Diseases–10 Classification of Illness: A Systematic Review and Meta-analysis With a Proposal for Revised FUO Classification
Authors: Wright William F , Wang Jiangxia , Auwaerter Paul G
Published: February 2023

Background

Classifying fever of unknown origin (FUO) into categorical etiologies (ie, infections, noninfectious inflammatory, oncologic, miscellaneous, and undiagnosed disorders) remains unstandardized and subject to discrepancies. As some disease classifications change, a systematic review of studies would help physicians anticipate the frequency of illness types they may encounter that could influence care.

Methods

We systematically reviewed prospective FUO studies published across the Medline (PubMed), Embase, Scopus, and Web of Science databases from January 1, 1997, to July 31, 2022. We performed a meta-analysis to estimate associated pooled proportions between the investigator-determined choice of disease category and those determined by the International Classification of Diseases, 10th edition (ICD-10), methodology.

Results

The proportion of patients with a difference between the investigator and ICD-10-adjusted noninfectious inflammatory disorder category was 1.2% (95% CI, 0.005–0.021; P < .001), and the proportion was similar for the miscellaneous category at 1.5% (95% CI, 0.007–0.025; P < .001). The miscellaneous and noninfectious inflammatory disorders categories demonstrated significant across-study heterogeneity in the proportions of patients changing categories, with 52.7% (P = .007) and 51.0% (P = .010) I2, respectively.

Conclusions

Adjusting FUO-associated diagnoses by ICD-10 methodology was associated with a statistically significant risk of over- or underestimation of disease category frequency approximation when using a 5 FUO category system. An FUO diagnostic classification system that better reflects mechanistic understanding would assist future research and enhance comparability across heterogenous populations and different geographic regions. We propose an updated FUO classification scheme that streamlines categorizations, aligns with the current understanding of disease mechanisms, and should facilitate empirical decisions, if necessary.
Optimal Duration of Systemic Corticosteroids in Coronavirus Disease 2019 Treatment: A Systematic Review and Meta-analysis
Authors: Ssentongo Paddy , Yu Nyein , Voleti Navya , Reddy Surya , Ingram David , Chinchilli Vernon M , Paules Catharine I
Published: February 2023

Background

Corticosteroids confer a survival benefit in individuals hospitalized with coronavirus disease 2019 (COVID-19) who require oxygen. This meta-analysis seeks to determine the duration of corticosteroids needed to optimize this mortality benefit.

Methods

Electronic databases were searched to 9 March 2022, for studies reporting corticosteroid versus no corticosteroid treatment in hospitalized COVID-19 patients. We estimated the effect of corticosteroids on mortality by random-effects meta-analyses. Subgroup analyses and meta-analyses were conducted to assess the optimal duration of corticosteroid treatment while adjusting for the severity of disease, age, duration of symptoms, and proportion of control group given steroids.

Results

We identified 27 eligible studies consisting of 13 404 hospitalized COVID-19 patients. Seven randomized controlled trials and 20 observational studies were included in the meta-analysis of mortality, which suggested a protective association with corticosteroid therapy (risk ratio [RR], 0.71 [95% confidence interval {CI}, .58–.87]). Pooled analysis of 18 studies showed the greatest survival benefit for a treatment duration up to 6 days (RR, 0.54 [95% CI, .39–.74]). Survival benefit was 0.65 (95% CI, .51–.83) up to 7 days, and no additional survival benefit was observed beyond 7 days of treatment (RR, 0.64 [95% CI, .44–.93]). The survival benefit was not confounded by severity of disease, age, duration of symptoms, or proportion of control group given steroids.

Conclusions

In this meta-analysis, optimal duration of corticosteroid treatment for hospitalized COVID-19 patients was up to 6 days, with no additional survival benefit with >7 days of treatment.
Insights into cell wall changes during fruit softening from transgenic and naturally occurring mutants
Authors: Shi Yanna , Li Bai-Jun , Grierson Donald , Chen Kun-Song
Published: February 2023

Excessive softening during fleshy fruit ripening leads to physical damage and infection that reduce quality and cause massive supply chain losses. Changes in cell wall (CW) metabolism, involving loosening and disassembly of the constituent macromolecules, are the main cause of softening. Several genes encoding CW metabolizing enzymes have been targeted for genetic modification to attenuate softening. At least 9 genes encoding CW-modifying proteins have increased expression during ripening. Any alteration of these genes could modify CW structure and properties and contribute to softening, but evidence for their relative importance is sparse. The results of studies with transgenic tomato (Solanum lycopersicum), the model for fleshy fruit ripening, investigations with strawberry (Fragaria spp.) and apple (Malus domestica), and results from naturally occurring textural mutants provide direct evidence of gene function and the contribution of CW biochemical modifications to fruit softening. Here we review the revised CW structure model and biochemical and structural changes in CW components during fruit softening and then focus on and integrate the results of changes in CW characteristics derived from studies on transgenic fruits and mutants. Potential strategies and future research directions to understand and control the rate of fruit softening are also discussed.
The impact of health literacy: associations with disease activity and medication prescription in patients with rheumatoid arthritis
Authors: Gorter Anne , Bakker Mark M , ten Klooster Peter M , Boonen Annelies , Vonkeman Harald E
Published: February 2023

Objective

The aim of this study was to explore the longitudinal associations between health literacy profiles and disease activity and medication prescription in patients with RA.

Methods

Patients with RA who previously completed the Health Literacy Questionnaire (HLQ) and were assigned 1 of 10 distinct health literacy profiles based on cluster analysis were further aggregated into three groups: ‘several health literacy limitations’, ‘some health literacy limitations’ and ‘good health literacy’. Linear mixed modelling (LMM) was used to analyse the association between health literacy groups and disease activity over the course of 1 year. Chi-squared tests and logistic regression analyses were used to compare medication prescriptions between the groups.

Results

A total of 108 patients with RA were included. LMM showed a significant effect of health literacy group on disease activity over time (P = 0.010). Patients with ‘good health literacy’ had significantly lower disease activity over time [28-joint DAS with ESR (DAS28-ESR) = 2.4] than patients with ‘several health literacy limitations’ (DAS28-ESR = 3.1), independent of age, gender and education level. Patients with ‘good health literacy’ were most often prescribed a biologic DMARD (50%), whereas patients with ‘some health literacy limitations’ more commonly received a conventional synthetic DMARD only [72.7%; odds ratio (OR) 4.24], and patients with ‘several health literacy limitations’ were more often prescribed prednisolone (52.4%; OR 3.56).

Conclusion

Significant differences in longitudinal disease activity and medication prescription were observed between groups with different health literacy levels. These results stress the importance of insights into the role of health literacy in treatment and outcomes in patients with RA.
Morphological and Molecular Characterization, Including Parasitic and Pathogenic Studies of a New Spherical Cyst Nematode Species, Globodera vulgaris n. sp. (Nematoda: Heteroderidae), Associated with Potatoes in China
Authors: Xu Chunling , Yang Sihua , Xie Yujia , He Jin , Chen Yan , Pan Yonglang , Xie Hui
Published: February 2023

In this study, a new spherical cyst nematode belonging to the genus Globodera, herein described as Globodera vulgaris n. sp., was extracted from the roots and rhizosphere soil of potato and circumjacent weeds belonging to different families in three provinces in southwest China. The new species was characterized by 8 to 24 ridges between the anus and fenestra and an average Granek's ratio of 2.8 to 3.8 in cysts, a head with three to four annules, a dorsal knob anteriorly projected, ventral knobs round or anteriorly projected in second stage juveniles, a head with three to five annules, a short spicule with an average length of less than 30.0 μm, and a developed velum in males. Pathogenicity tests showed that G. vulgaris n. sp. infected potato but did not damage or affect the potato yield compared with the control, and it parasitized tomato with a low reproduction rate (RF < 1) while it did not parasitize tobacco (RF = 0). The new species was closely related to G. rostochiensis, based on molecular diagnostic marker sequences and constructed phylogenetic analysis, based on internal transcribed spacers of ribosomal DNA, large-subunit rDNA, and small-subunit rDNA. However, the new species exhibited differences from G. rostochiensis in terms of morphological characteristics, a wide host preference, lack of damage to hosts, and an egg-hatching rate induced by hatching factors.