bluuebunny/crossref_metadata_2025 huggingface dataset:
Amygdala hyperactivation relates to eating behaviour: a potential indicator of food addiction in Prader–Willi syndrome
Authors: Strelnikov Kuzma , Debladis Jimmy , Salles Juliette , Valette Marion , Cortadellas Julie , Tauber Maithé , Barone Pascal
Published: April 2023

Prader–Willi syndrome is a rare neurodevelopmental genetic disorder characterized by various endocrine, cognitive and behavioural problems. The symptoms include an obsession for food and reduced satiety, which leads to hyperphagia and morbid obesity. Neuropsychological studies have reported that Prader–Willi patients display altered social interactions with a specific weakness in interpreting social information and responding to them, a symptom close to that observed in autism spectrum disorders. In the present case-control study, we hypothesized that brain regions associated with compulsive eating behaviour would be abnormally activated by food-related odours in Prader–Willi syndrome, as these can stimulate the appetite and induce hunger-related behaviour. We conducted a brain imaging study using the olfactory modality because odours have a high-hedonic valence and can cause stronger emotional reactions than other modalities. Further, the olfactory system is also intimately associated with the endocrine regulation of energy balance and is the most appropriate modality for studies of Prader–Willi syndrome. A total of 16 Prader–Willi participants were recruited for this study, which is a significant achievement given the low incidence rate of this rare disease. The second group of 11 control age-matched subjects also participated in the brain imaging study. In the MRI scanner, using an MRI-compatible olfactometer during 56 block sessions, we randomly presented two odours (tulip and caramel), which have different hedonic valence and a different capacity to arouse hunger-related behaviour. Our results demonstrate that Prader–Willi participants have abnormal activity in the brain reward system that regulates eating behaviour. Indeed, we found that these patients had right amygdala activity up to five times higher in response to a food odour (caramel) compared with the tulip odour. In contrast, age-matched control participants had similar activity levels in response to both odours. The amygdala activity levels were found to be associated with the severity of the hyperphagia in Prader–Willi patients. Our results provide evidence for functional alteration of the right amygdala in Prader–Willi syndrome, which is part of the brain network involved in food addiction modulated by the ghrelin and oxytocin systems, which may drive the hyperphagia. Our study provides important new insights into the functioning of emotion-related brain circuits and pathology, and it is one of the few to explore the dysfunction of the neural circuits involved in emotion and addiction in Prader–Willi syndrome. It suggests new directions for the exploration and remediation of addictive behaviours.
Neural grafts containing exosomes derived from Schwann cell-like cells promote peripheral nerve regeneration in rats
Authors: Hu Taotao , Chang Shusen , Qi Fang , Zhang Zhonghui , Chen Jiayin , Jiang Lingli , Wang Dali , Deng Chengliang , Nie Kaiyu , Xu Guangchao , Wei Zairong
Published: April 2023

Background

Schwann cell-like cells (SCLCs), differentiated from mesenchymal stem cells, have shown promising outcomes in the treatment of peripheral nerve injuries in preclinical studies. However, certain clinical obstacles limit their application. Hence, the primary aim of this study was to investigate the role of exosomes derived from SCLCs (SCLCs-exo) in peripheral nerve regeneration.

Methods

SCLCs were differentiated from human amniotic mesenchymal stem cells (hAMSCs) in vitro and validated by immunofluorescence, real-time quantitative PCR and western blot analysis. Exosomes derived from hAMSCs (hAMSCs-exo) and SCLCs were isolated by ultracentrifugation and validated by nanoparticle tracking analysis, WB analysis and electron microscopy. A prefabricated nerve graft was used to deliver hAMSCs-exo or SCLCs-exo in an injured sciatic nerve rat model. The effects of hAMSCs-exo or SCLCs-exo on rat peripheral nerve injury (PNI) regeneration were determined based on the recovery of neurological function and histomorphometric variation. The effects of hAMSCs-exo or SCLCs-exo on Schwann cells were also determined via cell proliferation and migration assessment.

Results

SCLCs significantly expressed the Schwann cell markers glial fibrillary acidic protein and S100. Compared to hAMSCs-exo, SCLCs-exo significantly enhanced motor function recovery, attenuated gastrocnemius muscle atrophy and facilitated axonal regrowth, myelin formation and angiogenesis in the rat model. Furthermore, hAMSCs-exo and SCLCs-exo were efficiently absorbed by Schwann cells. However, compared to hAMSCs-exo, SCLCs-exo significantly promoted the proliferation and migration of Schwann cells. SCLCs-exo also significantly upregulated the expression of a glial cell-derived neurotrophic factor, myelin positive regulators (SRY-box transcription factor 10, early growth response protein 2 and organic cation/carnitine transporter 6) and myelin proteins (myelin basic protein and myelin protein zero) in Schwann cells.

Conclusions

These findings suggest that SCLCs-exo can more efficiently promote PNI regeneration than hAMSCs-exo and are a potentially novel therapeutic approach for treating PNI.
Sluggish investment, crisis and firm heterogeneity
Authors: Arrighetti Alessandro , Landini Fabio
Published: April 2023

The stagnation of investments and its causes have attracted great attention in the recent economic debate. In this paper, we show that during the Great Recession, the flattening of the capital formation rate at the firm level is not due to lower average propensity to invest. Rather, it is the result of growing heterogeneity of choices among firms. While a subset of firms is oriented towards increasing investments, another group substantially divest. The result is a polarization of conducts that tend to cancel each other out, resulting in a flattening of aggregate investment. We argue that this asymmetry in firm’s decisions depends on two main factors. The first one is the diversity of corporate strategies, which firms have developed in the past. The second driver is managerial discretion, that plays an important role in the adoption of specific investment/divestment trajectories when faced with a recession. The results of our empirical analysis provide strong support for our hypotheses: after controlling for contextual and firm-specific structural, financial and demographic variables, corporate strategies and managerial discretion in the allocation of liquid assets explain large part of the heterogeneity in investment decisions during the recession. Policy implications are discussed.
Analytical and Non-Analytical Variation May Lead to Inappropriate Antimicrobial Dosing in Neonates: An In Silico Study
Authors: Nguyen Thi A , Kirubakaran Ranita , Schultz Hayley B , Wong Sherilyn , Reuter Stephanie E , McMullan Brendan , Bolisetty Srinivas , Campbell Craig , Horvath Andrea R , Stocker Sophie L
Published: April 2023

Background

Therapeutic drug monitoring (TDM) of aminoglycosides and vancomycin is used to prevent oto- and nephrotoxicity in neonates. Analytical and nonanalytical factors potentially influence dosing recommendations. This study aimed to determine the impact of analytical variation (imprecision and bias) and nonanalytical factors (accuracy of drug administration time, use of non-trough concentrations, biological variation, and dosing errors) on neonatal antimicrobial dosing recommendations.

Methods

Published population pharmacokinetic models and the Australasian Neonatal Medicines Formulary were used to simulate antimicrobial concentration–time profiles in a virtual neonate population. Laboratory quality assurance data were used to quantify analytical variation in antimicrobial measurement methods used in clinical practice. Guideline-informed dosing recommendations based on drug concentrations were applied to compare the impact of analytical variation and nonanalytical factors on antimicrobial dosing.

Results

Analytical variation caused differences in subsequent guideline-informed dosing recommendations in 9.3−12.1% (amikacin), 16.2−19.0% (tobramycin), 12.2−45.8% (gentamicin), and 9.6−19.5% (vancomycin) of neonates. For vancomycin, inaccuracies in drug administration time (45.6%), use of non-trough concentrations (44.7%), within-subject biological variation (38.2%), and dosing errors (27.5%) were predicted to result in more dosing discrepancies than analytical variation (12.5%). Using current analytical performance specifications, tolerated dosing discrepancies would be up to 14.8% (aminoglycosides) and 23.7% (vancomycin).

Conclusions

Although analytical variation can influence neonatal antimicrobial dosing recommendations, nonanalytical factors are more influential. These result in substantial variation in subsequent dosing of antimicrobials, risking inadvertent under- or overexposure. Harmonization of measurement methods and improved patient management systems may reduce the impact of analytical and nonanalytical factors on neonatal antimicrobial dosing.
Hemostatic protocol and risk-reduction surgery for treating coronary artery disease with aortic stenosis in a patient with combined coagulation factor VIII and XI deficiency: a case report
Authors: Honda Sayaka , Shimahara Yusuke , Chikasawa Yushi , Ogino Hitoshi
Published: April 2023

Background

Cardiac surgery remains a significant challenge in patients with coagulation factor VIII (FVIII) deficiency, especially in those with multiple factor deficiencies.

Case summary

A 79-year-old man with combined FVIII and factor XI (FXI) deficiency was admitted for heart failure treatment. Transthoracic echocardiography revealed aortic stenosis (AS) with decreased left ventricular ejection fraction (LVEF) of 40%, mean aortic pressure gradient of 21 mmHg, and aortic valve area of 0.58 cm2. Coronary angiography revealed significant triple-vessel disease. The patient had multiple comorbidities, including diabetic end-stage renal disease treated with hemodialysis and liver cirrhosis (Child–Pugh score of A). Considering the high surgical risk, a two-stage treatment strategy was developed: the first with off-pump coronary artery bypass grafting (CABG), and the second with transcatheter aortic valve implantation if AS symptoms were significant after CABG. A perioperative hemostatic protocol by the author’s heart team was used to appropriately replenish recombinant FVIII concentrates and fresh frozen plasma. The target preoperative and postoperative FVIII coagulation activity values were set at 80–100% and 60–80%, respectively, whereas the target perioperative FXI coagulation activity value was set at 30–45%. Off-pump CABG without aortic manipulation was completed without bleeding events. Transthoracic echocardiography conducted 20 months postoperatively revealed LVEF of 65% and mean aortic pressure gradient of 31 mmHg. The patient leads a normal life 21 months after surgery.

Discussion

The hemostatic protocol and risk-reduction surgery provided satisfactory surgical results in a patient with significant coronary artery disease and AS, high-surgical-risks, and combined FVIII and FXI deficiency.
Early recurrence of attack after myocardial infarction with non-obstructive coronary arteries: a case report
Authors: Morooka Masaki , Kurihara Osamu , Takano Masamichi , Miyauchi Yasushi
Published: April 2023

Background

Diagnostic strategies depend on non-standardized workup, and the causes of myocardial infarction with non-obstructive coronary arteries remain unclear for some patients. Intracoronary imaging is recommended for detecting the missed causes by coronary angiography. Myocardial infarction with non-obstructive coronary arteries is a heterogeneous entity; a meta-analysis of myocardial infarction with non-obstructive coronary artery studies demonstrated that all-cause mortality rate at 1 year is 4.7%, and its prognosis is not so favourable.

Case summary

A 62-year-old man without remarkable medical history complained of acute chest pain at rest, which resolved at his arrival. Although echocardiography and electrocardiogram exhibited normal findings, the concentration of high-sensitive cardiac troponin T increased up to 0.384 from 0.04 ng/mL. Coronary angiography was performed, and mild stenosis of the proximal right coronary artery was detected. He was discharged without catheter intervention and medications as he reported no symptoms. He returned 8 days later because of inferoposterior ST-segment elevation myocardial infarction with ventricular fibrillation. Emergent coronary angiography showed that the mild stenosis of the proximal right coronary artery had progressed to total occlusion. Optical coherence tomography after thrombectomy revealed rupture of the thin-cap fibroatheroma and protruding thrombus.

Discussion

Patients presenting with myocardial infarction with non-obstructive coronary arteries and plaque disruption and/or thrombus detected by optical coherence tomography do not show normal coronaries on coronary angiography. Aggressive investigation into plaque disruption using intracoronary imaging is recommended even if coronary angiography demonstrates mild stenosis to prevent a fatal attack for suspicious cases of myocardial infarction with non-obstructive coronary arteries.
Strong selection is poorly aligned with genetic variation in Ipomoea hederacea: implications for divergence and constraint
Authors: Henry Georgia A , Stinchcombe John R
Published: April 2023

The multivariate evolution of populations is the result of the interactions between natural selection, drift, and the underlying genetic structure of the traits involved. Covariances among traits bias responses to selection, and the multivariate axis which describes the greatest genetic variation is expected to be aligned with patterns of divergence across populations. An exception to this expectation is when selection acts on trait combinations lacking genetic variance, which limits evolutionary change. Here we used a common garden field experiment of individuals from 57 populations of Ipomoea hederacea to characterize linear and nonlinear selection on 5 quantitative traits in the field. We then formally compare patterns of selection to previous estimates of within population genetic covariance structure (the G-matrix) and population divergence in these traits. We found that selection is poorly aligned with previous estimates of genetic covariance structure and population divergence. In addition, the trait combinations favored by selection were generally lacking genetic variation, possessing approximately 15%–30% as much genetic variation as the most variable combination of traits. Our results suggest that patterns of population divergence are likely the result of the interplay between adaptive responses, correlated responses, and selection favoring traits lacking genetic variation.
The Environmental Audit Screening Evaluation: Establishing Reliability and Validity of an Evidence-Based Design Tool
Authors: Kaup Migette L , Calkins Margaret P , Davey Adam , Wrublowsky Robert
Published: April 2023

Background and Objectives

Current assessment tools for long-term care environments have limited generalizability or ability to be linked to specific quality outcomes. To discriminate between different care models, tools are needed to assess important elements of the environmental design. The goal of this project was to systematically evaluate the reliability and validity of the Environmental Audit Screening Evaluation (EASE) tool to better enable the identification of best models in long-term care design to maintain quality of life for persons with dementia and their caregivers.

Research Design and Methods

Twenty-eight living areas (LAs) were selected from 13 sites similar in organizational/operational commitment to person-centered care but with very different LA designs. LAs were stratified into 3 categories (traditional, hybrid, and household) based primarily on architectural/interior features. Three evaluators rated each LA using the Therapeutic Environment Screening Scale (TESS-NH), Professional Environmental Assessment Protocol (PEAP), Environmental Audit Tool (EAT-HC), and EASE. One of each type of LA was reassessed approximately 1 month after the original assessment.

Results

EASE scores were compared against the scores of 3 existing tools to evaluate its construct validity. The EAT-HC was most closely related to the EASE (r = 0.88). The PEAP and the TESS-NH were less correlated to the EASE (r = 0.82 and 0.71, respectively). Analysis of variance indicated that the EASE distinguished between traditional and home-like settings (0.016), but not hybrid LAs. Interrater and inter-occasion reliability and agreement of the EASE were consistently high.

Discussion and Implications

Neither of the 2 U.S.-based existing environmental assessment tools (PEAP and TESS-NH) discriminated between the 3 models of environments. The EAT-HC was most closely aligned with the EASE and performed similarly in differentiating between the traditional and household models, but the dichotomous scoring of the EAT-HC fails to capture environmental nuances. The EASE tool is comprehensive and accounts for nuanced design differences across settings.
Reply to comment on Malkoti et al. () by Haney and Nakahara
Authors: Datta Arjun
Published: April 2023

We acknowledge errors in the surface wave Green's tensor shown by Malkoti et al., as pointed out in the Comment by Haney and Nakahara. Using their expressions for Love and Rayleigh wave Green's tensors valid in the near-field, we recompute multicomponent cross-correlation waveforms required for H/V amplitude ratio calculations. All else being equal, these new waveforms are practically indistinguishable from those of Malkoti et al. Differences due to the use of corrected Green's tensors, appear only when the receivers are placed close to the edges of the modelling domain, that is when the receiver separation is large compared to the domain size. Since Malkoti et al. used a modelling domain much larger than the receiver separation, their H/V calculations, and all associated findings, stand.
Association between minimum inhibitory concentration values and mortality risk in patients with Stenotrophomonas maltophilia infections: a retrospective cohort study of electronic health records from 148 US hospitals
Authors: Sarzynski Sadia H , Lawandi Alexander , Warner Sarah , Demirkale Cumhur Y , Strich Jeffrey R , Dekker John P , Babiker Ahmed , Li Willy , Kadri Sameer S
Published: April 2023

Background

Clinical data informing antimicrobial susceptibility breakpoints for Stenotrophomonas maltophilia infections are lacking. We sought to leverage real-world data to identify MIC values within the currently defined susceptible range that could discriminate mortality risk for patients with S. maltophilia infections and guide future breakpoint revisions.

Methods

Inpatients with S. maltophilia infection who received single-agent targeted therapy with levofloxacin or trimethoprim/sulfamethoxazole were identified in the Cerner HealthFacts electronic health record database. Encounters were restricted to those with MIC values reported to be in the susceptible range for both agents. Curation for exact (non-range) MIC values yielded sequentially granular model populations. Logistic regression was used to calculate adjusted OR (aOR) of mortality or hospice discharge associated with different susceptible-range MICs, controlling for patient- and centre-related factors, and infection site, polymicrobial infection and receipt of empirical therapy.

Results

Seventy-three of 851 levofloxacin-treated patients had levofloxacin MIC of exactly 2 mg/L (current Clinical and Laboratory Standards Institute (CLSI) susceptibility breakpoint) and served as the reference category for levofloxacin breakpoint models. In breakpoint model I (n = 501), aOR of mortality associated with infection due to isolates with levofloxacin MIC of ≤1 versus 2 mg/L were similar [aOR = 1.79 (95% CI 0.88–3.62), P = 0.11]. In breakpoint model IIa (n = 358), aOR of mortality associated with MIC ≤0.5 versus 2 mg/L were also similar [aOR 0.1.36 (95% CI 0.65–2.83), P = 0.41]. However, breakpoint model IIb (n = 297) displayed higher aOR of mortality associated with an MIC of 1 versus 2 mg/L [aOR 2.36 (95% CI 1.14–4.88), P = 0.02]. Only 9/645 trimethoprim/sulfamethoxazole-treated patients had trimethoprim/sulfamethoxazole MIC of exactly 2/38 mg/L precluding informative models for this agent.

Conclusions

In this retrospective study of real-world patients with S. maltophilia infection, risk-adjusted survival data do not appear to stratify patients clinically within current susceptible-range MIC breakpoint for levofloxacin (≤2 mg/L) by mortality.
Oroxylin a glucuronide as a novel class of reversible inhibitors of Sortase a, combats MRSA-induced infections
Authors: Jiang Xin , Kong Xiangri , Wang Xingye , Yu Zishu , Guo Xuerui , Jin Mengli , Chen Xiaoyu , Guan Jiyu , Wu Cui , Wei Lin , Zhang Chi , Song Guangqi , Jiang Tao , Wang Li , Zhao Yicheng , Song Wu
Published: April 2023

Aims

The main purpose of this study was to study the therapeutical effect of oroxylin A glucuronide (OAG) on methicillin-resistant Staphylococcus aureus (MRSA).

Methods and results

By substrate peptide reaction-based fluorescence resonance energy transfer (FRET) screening, we identified that OAG was an efficient inhibitor of Sortase A (SrtA) with an IC50 of 45.61 μg mL−1, and achieved efficacy in the treatment of Staphylococcus aureus (S. aureus) infections. We further demonstrated that OAG inhibited the adhesion of the S. aureus to fibrinogen, the surface protein A anchoring and diminished biofilm formation. Results obtained from fluorescence quenching assay elucidated a direct interaction between OAG and SrtA. Employing molecular dynamics simulations, we proved that OAG binds to the binding sites of R197, G192, E105, and V168 in the SrtA. Notably, OAG exhibited a robust therapeutic effect in a MRSA-induced pneumonia model.

Conclusions

We identified that OAG as a novel class of reversible inhibitors of SrtA, combats MRSA-induced Infections.
Change at the Top: The Necessity of Transitional Leadership Provisions in the Laws of Independent State-Based Institutions
Authors: Roberts Lyer Kirsten
Published: April 2023

The leadership of independent state-based bodies is critical to their independence and proper functioning. Where leadership ends, either within or outside of the term of office, legislation must ensure that the institution can continue to function. Transitional leadership provisions provide for the continuation of the powers of office in the event of the absence of the mandate holder. Through a textual analysis of the legislation of National Human Rights Institutions (NHRIs) and ombudspersons from 85 jurisdictions, this article identifies a lack of provision for transitional arrangements in enabling laws. It also discusses the problematic aspects of these legislative arrangements where they are present. It identifies the core requirements to ensure there is no leadership gap for an institution. The findings of the article are relevant for a broad range of state-based institutions including anti-corruption and data protection commissions, equality bodies and police oversight bodies, because all state mandated institutions risk their ability to function being undermined where legislation fails to account for a gap in leadership or does not include sufficient protections, such as immunity, for transitional office holders. This article calls for more robust focus on comprehensive transitional provisions in international standards on NHRIs and ombudspersons, and for the inclusion of such transitional provisions in the enabling laws of all legislatively mandated independent state-based institutions.
The efficacy and safety of trastuzumab deruxtecan (T-DXd) in HER2-expressing solid tumours: a single-arm meta-analysis
Authors: Kou Liqiu , Chen Xiu , Xie Xiaolu , Wen Qinglian , Li Jun , Li Yaling
Published: April 2023

Objective

We performed a meta-analysis to assess the efficacy and safety of T-DXd in the treatment of HER2-expressing solid tumours.

Methods

We systematically searched PubMed, Web of Science, Embase and the Cochrane Library and collected studies published before March 17, 2023, on T-DXd for HER2-expressing tumours for a meta-analysis. We performed a subgroup analysis based on the different cancer types and the doses used.

Results

There were 11 studies including 1349 HER2-expressing patients in this meta-analysis. The pooled ORR was 47.91%, and the pooled DCR was 87.01%. The mPFS and mOS combined were 9.63 and 10.71 months, respectively. The most common adverse reactions in grades 1–2 were decreased appetite (49.3%) and vomiting (43.0%). The netropemia (31.2%) and leukopenia (31.2%) were the most common grade 3 and higher adverse reactions. Subgroup analysis showed that breast cancer had the best ORR and DCR, with 66.96 and 96.52%, respectively.

Conclusions

Overall, the efficacy of T-DXd in treating HER2-expressing solid tumours is encouraging, especially breast and non-small cell lung cancers, and has an acceptable safety profile. However, concerns remain about potentially serious treatment adverse events (e.g. interstitial lung disease/pneumonia). More well-designed, large-scale randomized controlled trials are needed to demonstrate our study.
Perspectives of pharmacists and patients on pharmacist services to improve medication adherence among patients with diabetes in Indonesia
Authors: Presley Bobby , Groot Wim , Setiawan Eko , Pavlova Milena
Published: April 2023

Objectives

Pharmacists’ role in diabetes care is developing in improving medication adherence. Implementation of pharmacist services needs to consider patients’ and pharmacists’ perspectives as service users and providers, respectively. Therefore, this study investigates both perspectives on suitable pharmacist services to improve medication adherence in Indonesia.

Methods

This study used data collected based on open-ended survey questions, which were part of a survey among 917 patients and 99 pharmacists in community health centres (CHCs) and three hospitals in Surabaya, Indonesia. The open-ended questions aimed to elicit the perspective of patients and pharmacists on pharmacist services. The data were digitally recorded, transcribed and analysed in Atlas.ti 9th software using a pre-defined coding book. The data were then quantified.

Key findings

Most patients indicated they did not need services to improve medication adherence (67.25% CHCs vs. 63.06% hospitals). Those who did need services mostly preferred educational-based pharmacist services. This was also pharmacists’ most frequently mentioned service (45.45%). Consultation/counselling was the most common service to improve adherence according to pharmacists (66.67%) and patients (15.53% CHCs vs. 19.89% hospitals). Reminders about medication use and providing discussion sessions/seminars, and home care were other options mentioned. Limited human resources, time and pharmacists’ high workload were the most commonly identified barriers to implementing the desired pharmacist services.

Conclusion

Patients and pharmacists had similar perspectives on the desired services to improve medication adherence, especially educational-based services and consultation/counselling. Barriers to implementing services should be considered when evaluating the current practice and preparing for pharmacists’ future role in patient care.
Taming Pereboom’s Wild Coincidences
Authors: Müller Thomas
Published: April 2023

Pereboom’s ‘wild coincidences’ argument against agent-causal libertarianism is based on the claim that in a world governed by statistical laws, the dovetailing of indeterministic physical happenings with the free actions of agent causes would be a coincidence too wild to be credible. In this paper it is shown that the conclusion is valid for deterministic laws, but that it fails for statistical laws. Therefore, the ‘wild coincidences’ argument does not provide the promised empirical refutation of agent-causal libertarianism.
Thermodynamic properties of small flares in the quiet Sun observed by Hα and EUV: plasma motion of the chromosphere and time evolution of temperature/emission measure
Authors: Kotani Yuji , Ishii T T , Yamasaki D , Otsuji K , Ichimoto K , Asai A , Shibata K
Published: April 2023

Small flares frequently occur in the quiet Sun. Previous studies have noted that they share many common characteristics with typical solar flares in active regions. However, their similarities and differences are not fully understood, especially their thermal properties. In this study, we performed imaging spectroscopic observations in the Hα line taken with the Solar Dynamics Doppler Imager on the Solar Magnetic Activity Research Telescope (SMART/SDDI) at the Hida Observatory and imaging observations with the Atmospheric Imaging Assembly onboard Solar Dynamics Observatory (SDO/AIA). We analysed 25 cases of small flares in the quiet Sun over the thermal energy range of $10^{24}{\!-\!}10^{27}\, \mathrm{erg}$ , paying particular attention to their thermal properties. Our main results are as follows: (1) We observe a redshift together with line centre brightening in the Hα line associated with more than half of the small flares. (2) We employ differential emission measure analysis using AIA multitemperature (channel) observations to obtain the emission measure and temperature of the small flares. The results are consistent with the Shibata & Yokoyama (1999, 2002) scaling law. From the scaling law, we estimated the coronal magnetic field strength of small flares to be 5–15 G. (3) The temporal evolution of the temperature and the density shows that the temperature peaks precede the density peaks in more than half of the events. These results suggest that chromospheric evaporations/condensations play an essential role in the thermal properties of some of the small flares in the quiet Sun, as does for large flares.
Multimass modelling of Milky Way globular clusters – I. Implications on their stellar initial mass function above 1 M⊙
Authors: Dickson N , Hénault-Brunet V , Baumgardt H , Gieles M , Smith P J
Published: April 2023

The distribution of stars and stellar remnants (white dwarfs, neutron stars, and black holes) within globular clusters holds clues about their formation and long-term evolution, with important implications for their initial mass function (IMF) and the formation of black hole mergers. In this work, we present best-fitting multimass models for 37 Milky Way globular clusters, which were inferred from various data sets, including proper motions from Gaia EDR3 and HST, line-of-sight velocities from ground-based spectroscopy and deep stellar mass functions from HST. We use metallicity-dependent stellar evolution recipes to obtain present-day mass functions of stars and remnants from the IMF. By dynamically probing the present-day mass function of all objects in a cluster, including the mass distribution of remnants, these models allow us to explore in detail the stellar (initial) mass functions of a large sample of Milky Way GCs. We show that, while the low-mass mass function slopes are strongly dependent on the dynamical age of the clusters, the high-mass slope (α3; m > 1 M⊙) is not, indicating that the mass function in this regime has generally been less affected by dynamical mass loss. Examination of this high-mass mass function slope suggests an IMF in this mass regime consistent with a Salpeter IMF is required to reproduce the observations. This high-mass IMF is incompatible with a top-heavy IMF, as has been proposed recently. Finally, based on multimass model fits to our sample of Milky Way GCs, no significant correlation is found between the high-mass IMF slope and cluster metallicity.
Stirred, not shaken: star cluster survival in the slingshot scenario
Authors: Matus Carrillo D R , Fellhauer M , Boekholt T C N , Stutz A , Morales Inostroza M C B
Published: April 2023

We investigate the effects of an oscillating gas filament on the dynamics of its embedded stellar clusters. Motivated by recent observational constraints, we model the host gas filament as a cylindrically symmetrical potential, and the star cluster as a Plummer sphere. In the model, the motion of the filament will produce star ejections from the cluster, leaving star cluster remnants that can be classified into four categories: (a) filament-associated clusters, which retain most of their particles (stars) inside the cluster and inside the filament; (b) destroyed clusters, where almost no stars are left inside the filament, and there is no surviving bound cluster; (c) ejected clusters, that leave almost no particles in the filament, since the cluster leaves the gas filament; and (d) transition clusters, corresponding to those clusters that remain in the filament, but that lose a significant fraction of particles due to ejections induced by filament oscillation. Our numerical investigation predicts that the Orion Nebula cluster is in the process of being ejected, after which it will most likely disperse into the field. This scenario is consistent with observations which indicate that the Orion Nebula cluster is expanding, and somewhat displaced from the integral-shaped filament ridgeline.
Rotational state-changes in C5N− by collisions with He and H2
Authors: Biswas R , Giri K , González-Sánchez L , Gianturco F A , Lourderaj U , Sathyamurthy N , Veselinova A , Yurtsever E , Wester R
Published: April 2023

The anion C5N− is one of the largest linear (C,N)-bearing chains detected in the interstellar medium. Here we present and discuss the general features of new ab initio potential energy surfaces describing the interaction of this linear anion with He and H2. We employ a Legendre Polynomials expansion representation for the former and an artificial neural network fit for the latter. We then carry out quantum scattering calculations to yield rotationally inelastic cross-sections for collisions with He and H2, using relative translational energy values in the range of 0.1–300 cm−1. We then obtained the corresponding inelastic rate coefficients as a function of temperature covering the range from 1 to 100 K. The results for these two systems are compared with each other, as well as with the earlier results on the C3N− colliding with the same partners. We found that the final inelastic rate coefficients for this anion are all fairly large, those from collisions with H2 being the largest. The consequences of such findings on their non-equilibrium rotational populations in interstellar environments are discussed in our conclusions.
Witnessing the intracluster medium assembly at the cosmic noon in JKCS 041
Authors: Andreon S , Romero C , Aussel H , Bhandarkar T , Devlin M , Dicker S , Ladjelate B , Lowe I , Mason B , Mroczkowski T , Raichoor A , Sarazin C , Trinchieri G
Published: April 2023

In this work, we study the intracluster medium (ICM) of a galaxy cluster at the cosmic noon: JKCS 041 at z  = 1.803. A 28 h long Sunyaev-Zel’dovich (SZ) observation using MUSTANG-2 allows us to detect JKCS 041, even if intrinsically extremely faint compared to other SZ-detected clusters. We found that the SZ peak is offset from the X-ray centre by about 220 kpc in the direction of the brightest cluster galaxy, which we interpret as due to the cluster being observed just after the first passage of a major merger. JKCS 041 has a low central pressure and a low Compton Y compared to local clusters selected by their ICM, likely because the cluster is still in the process of assembly but also in part because of a hard-to-quantify bias in current local ICM-selected samples. JKCS 041 has a 0.5 dex fainter Y signal than another less massive z ∼ 1.8 cluster, exemplifying how much different weak-lensing mass and SZ mass can be at high redshift. The observations we present provide us with the measurement of the most distant resolved pressure profile of a galaxy cluster. Comparison with a library of plausibly descendants shows that JKCS 041 pressure profile will likely increase by about 0.7 dex in the next 10 Gyr at all radii.
Heat shock transcription factors demonstrate a distinct mode of interaction with mitotic chromosomes
Authors: Price Rachel M , Budzyński Marek A , Shen Junzhou , Mitchell Jennifer E , Kwan James Z J , Teves Sheila S
Published: April 2023

A large number of transcription factors have been shown to bind and interact with mitotic chromosomes, which may promote the efficient reactivation of transcriptional programs following cell division. Although the DNA-binding domain (DBD) contributes strongly to TF behavior, the mitotic behaviors of TFs from the same DBD family may vary. To define the mechanisms governing TF behavior during mitosis in mouse embryonic stem cells, we examined two related TFs: Heat Shock Factor 1 and 2 (HSF1 and HSF2). We found that HSF2 maintains site-specific binding genome-wide during mitosis, whereas HSF1 binding is somewhat decreased. Surprisingly, live-cell imaging shows that both factors appear excluded from mitotic chromosomes to the same degree, and are similarly more dynamic in mitosis than in interphase. Exclusion from mitotic DNA is not due to extrinsic factors like nuclear import and export mechanisms. Rather, we found that the HSF DBDs can coat mitotic chromosomes, and that HSF2 DBD is able to establish site-specific binding. These data further confirm that site-specific binding and chromosome coating are independent properties, and that for some TFs, mitotic behavior is largely determined by the non-DBD regions.
UBE2C promotes leptomeningeal dissemination and is a therapeutic target in brain metastatic disease
Authors: Paisana Eunice , Cascão Rita , Custódia Carlos , Qin Nan , Picard Daniel , Pauck David , Carvalho Tânia , Ruivo Pedro , Barreto Clara , Doutel Delfim , Cabeçadas José , Roque Rafael , Pimentel José , Miguéns José , Remke Marc , Barata João T , Faria Claudia C
Published: April 2023

Background

Despite current improvements in systemic cancer treatment, brain metastases (BM) remain incurable, and there is an unmet clinical need for effective targeted therapies.

Methods

Here, we sought common molecular events in brain metastatic disease. RNA sequencing of thirty human BM identified the upregulation of UBE2C, a gene that ensures the correct transition from metaphase to anaphase, across different primary tumor origins.

Results

Tissue microarray analysis of an independent BM patient cohort revealed that high expression of UBE2C was associated with decreased survival. UBE2C-driven orthotopic mouse models developed extensive leptomeningeal dissemination, likely due to increased migration and invasion. Early cancer treatment with dactolisib (dual PI3K/mTOR inhibitor) prevented the development of UBE2C-induced leptomeningeal metastases.

Conclusions

Our findings reveal UBE2C as a key player in the development of metastatic brain disease and highlight PI3K/mTOR inhibition as a promising anticancer therapy to prevent late-stage metastatic brain cancer.
Symmetry dictionary on charge and spin nonlinear responses for all magnetic point groups with nontrivial topological nature
Authors: Zhang Zhi-Fan , Zhu Zhen-Gang , Su Gang
Published: April 2023

Recently, charge or spin nonlinear transport with nontrivial topological properties in crystal materials has attracted much attention. In this paper, we perform a comprehensive symmetry analysis for all 122 magnetic point groups (MPGs) and provide a useful dictionary for charge and spin nonlinear transport from the Berry curvature dipole, Berry connection polarizability and Drude term with nontrivial topological nature. The results are obtained by conducting a full symmetry investigation of the matrix representations of six nonlinear response tensors. We further identify every MPG that can accommodate two or three of the nonlinear tensors. The present work gives a solid theoretical basis for an overall understanding of the second-order nonlinear responses in realistic materials.
A multifunctional nanocomposite hydrogel with controllable release behavior enhances bone regeneration
Authors: Mao Yingji , Zhang Yiwen , Wang Ying , Zhou Tao , Ma Bingxu , Zhou Pinghui
Published: April 2023

Autologous and allogeneic bone grafts remain the gold standard for repairing bone defects. However, donor shortages and postoperative infections contribute to unsatisfactory treatment outcomes. Tissue engineering technology that utilizes biologically active composites to accelerate the healing and reconstruction of segmental bone defects has led to new ideas for in situ bone repair. Multifunctional nanocomposite hydrogels were constructed by covalently binding silver (Ag+) core-embedded mesoporous silica nanoparticles (Ag@MSN) to bone morphogenetic protein-2 (BMP-2), which was encapsulated into silk fibroin methacryloyl (SilMA) and photo-crosslinked to form an Ag@MSN-BMP-2/SilMA hydrogel to preserve the biological activity of BMP-2 and slow its release. More importantly, multifunctional Ag+-containing nanocomposite hydrogels showed antibacterial properties. These hydrogels possessed synergistic osteogenic and antibacterial effects to promote bone defect repair. Ag@MSN-BMP-2/SilMA exhibited good biocompatibility in vitro and in vivo owing to its interconnected porosity and improved hydrophilicity. Furthermore, the multifunctional nanocomposite hydrogel showed controllable sustained-release activity that promoted bone regeneration in repairing rat skull defects by inducing osteogenic differentiation and neovascularization. Overall, Ag@MSN-BMP-2/SilMA hydrogels enrich bone regeneration strategies and show great potential for bone regeneration.
COMMERCIAL VOLTAGE INDICATOR AS A GAMMA RADIATION DETECTOR
Authors: Pejović Milić , Pejović Svetlana , Živanović Miloš
Published: April 2023

The paper analyses the possibility of commercial neon indicator lamp at low pressure application as a gamma radiation detector. The diode is most often used as an indicator in electrical switchers. The analysis was performed on the basis of experimental electrical breakdown time delay data as a function of relaxation time, applied voltage and gamma ray air kerma rate. It has been shown that the indicator can be used as a detector for relaxation time greater than 70 ms. During this time period, a complete recombination/de-excitation of the particles formed during previous breakdown and subsequent self-sustaining discharge, which can further initiate next breakdown, takes place. It was also shown that gamma radiation leads to a significant reduction in electrical breakdown time delay for applied voltages close to indicator breakdown voltage. Based on the behavior of the dependence of the mean value of the electrical breakdown time delay on the gamma ray air kerma rate, it was shown that the indicator can be used very efficiently as a detector up to air kerma rate of $\textsf{2.3}\cdot \textsf{10}^{-\textsf{5}}$ Gy/h, when the electrical breakdown time delay is measured for applied voltage 10% higher than the breakdown voltage.
Development of a Droplet Digital PCR Assay for Detection and Quantification of Stubby Root Nematode, Paratrichodorus allius, in Soil
Authors: Lawaju Bisho Ram , Yan Guiping , Whitworth Jonathan
Published: April 2023

The stubby root nematode Paratrichodorus allius is an important plant-parasitic nematode species within the Trichodoridae family. It can directly harm the plants by feeding on the roots or indirectly by transmitting Tobacco rattle virus. These nematodes are mostly diagnosed either by traditional microscopic methods or a polymerase chain reaction (PCR)-based method. Droplet digital PCR (ddPCR) is a novel PCR technique which is sensitive and precise in quantifying DNA templates of the test samples. In this study, we developed a ddPCR assay to detect and quantify P. allius in soil. The specificity and sensitivity of the assay was first determined using P. allius nematode DNA or DNA from sterilized soil artificially inoculated with P. allius, and the assay was used to quantify P. allius populations in field soils. The assay did not detect nematodes other than P. allius, thus showing high specificity. It was able to detect P. allius equivalent to a 0.01 and 0.02 portion of a single nematode in soil DNA and nematode DNA extracts, respectively. Highly linear relationships between DNA copy numbers from ddPCR and serial dilutions of known concentrations were observed with DNA from P. allius nematodes (R2 = 0.9842) and from artificially infested soil (R2 = 0.9464). The P. allius populations from field soils determined by ddPCR were highly correlated with traditional microscopic counts (R2 = 0.7963). To our knowledge, this is the first report of applying ddPCR to detect and quantify stubby root nematode in soil. The results of this study support the potentiality of a ddPCR assay as a new research tool in diagnostics of plant-parasitic nematodes.
Brief Communication on Pathologic Assessment of Persistent Stable Metastatic Lesions in Patients Treated With Anti-CTLA-4 or Anti-CTLA-4 + Anti-PD-1 Therapy
Authors: Buchbinder Elizabeth I. , Pfaff Kathleen L. , Turner Madison M. , Manos Michael , Ouyang Olivia , Ott Patrick A. , Giobbie-Hurder Anita , Rodig Scott J. , Hodi F. Stephen
Published: April 2023

Despite the wide use of immune checkpoint inhibition for the treatment of melanoma, the mechanisms leading to long-term stable disease are incompletely understood. Patients with metastatic melanoma who had received ipilimumab alone or ipilimumab plus nivolumab 2+years prior and attained at least 6 months of stable disease were identified. Positron emission tomography/computed tomography (PET/CT) was performed. Pretreatment and posttreatment biopsies of areas of stable disease were assessed for tumor, fibrosis, and inflammation. Seven patients underwent PET/CT and tissue biopsy. Fluorodeoxyglucose avid lesions on PET/CT ranged from no activity to an SUV of 22. In 6 patients, the residual stable lesions were composed of necrosis and fibrosis with a prominent pigment containing macrophages and no residual melanoma. In 1 patient, a nodal lesion demonstrated melanoma with active inflammation. In most patients with durable stable disease after treatment with ipilimumab or ipilimumab/nivolumab, residual lesions demonstrated predominantly necrosis and fibrosis consistent with resolving lesions. The presence of melanophages in these samples may suggest ongoing immune surveillance. One patient did demonstrate residual melanoma, indicating the need for ongoing monitoring of this patient population.