bluuebunny/crossref_metadata_2025 huggingface dataset:
Disruption in normal correlational patterns of metabolic networks in the limbic circuit during transient global amnesia
Authors: Segobin Shailendra , Renault Cyrielle , Viader Fausto , Eustache Francis , Pitel Anne Lise , Quinette Peggy
Published: March 2023

Transient global amnesia is characterized by the sudden apparition of severe episodic amnesia, mainly anterograde, associated with emotional changes. Even though the symptoms are stereotyped, cerebral mechanism underlying transient global amnesia remains unexplained and previous studies using positron emission tomography do not show any clear results or consensus on cerebral regions impacted during transient global amnesia. This study included a group of 10 transient global amnesic patients who underwent 18F-fluorodeoxyglucose positron emission tomography during the acute or recovery phase of the episode and 10 paired healthy controls. Episodic memory was evaluated with the encoding-storage-retrieval paradigm and a story recall test of the Wechsler’s memory scale and anxiety was assessed with the Spielberger scale. We used statistical parametric mapping to identify modifications of whole-brain metabolism. Regarding hypometabolism, there was no brain region systematically affected in all transient global amnesic patients and the comparison between amnesic patients and controls did not show any significant differences. To better understand the specific implication of the limbic circuit in the pathophysiology of transient global amnesia, we then conducted a correlational analysis that included regions of this network. Our findings showed that in healthy controls, regions of the limbic circuit seem to operate in a synchronized way with all regions being highly correlated to each other. On the opposite, in transient global amnesic patients, we observed a clear disruption of this normal correlational patterns between regions with the medial temporal lobe (the hippocampus, parahippocampal gyrus and amygdala) included in one cluster and the orbitofrontal cortex, anterior and posterior cingulate gyrus and thalamus gathered in the other one. Given the individual variability in the time course of transient global amnesia, the direct comparison between a group of patients and controls does not seem to favour the identification of subtle and transient alterations in regional metabolism. The involvement of an extended network, such as the limbic circuit, seems more likely to explain the symptoms of patients. Indeed, the synchronization of regions within the limbic circuit seems to be altered during transient global amnesia, which could explain the amnesia and anxiety observed in transient global amnesic patients. The present study thus deepens our understanding of the mechanisms underlying not only amnesia but also the emotional component of transient global amnesia by considering it as a disruption in the normal correlational patterns within the limbic circuit.
Longer-term outcomes of gastroesophageal reflux disease treated with magnetic sphincter augmentation
Authors: Puri Aiysha , Steven Sue , Markar Sheraz R , Boyle Nicholas
Published: March 2023

Surgical intervention for gastroesophageal reflux disease (GERD) has historically been limited to fundoplication. Magnetic sphincter augmentation (MSA) is a less invasive alternative that was introduced 15 years ago, and it may have a superior side-effect profile. To date, however, there has been just a single published study reporting outcomes in a UK population. This study reports quality-of-life (QOL) outcomes and antacid use in patients undergoing MSA, with a particular focus on postoperative symptoms and those with severe reflux. A single-center cohort study was carried out to assess the QOL outcomes and report long-term safety outcomes in patients undergoing MSA. GERD-health-related quality of life (GERD-HRQL) and Reflux Symptom Index (RSI) scores were collected preoperatively, and immediately postoperatively, at 1-, 2-, 3-, and 5-year follow-up time points. All patients underwent preoperative esophagogastroduodenoscopy, impedance, and manometry. Two hundred and two patients underwent laparoscopic MSA over 9 years. The median preoperative GERD-HRQL score was 31, and the median RSI score was 17. There was a reduction in all scores from preoperative values to each time point, which was sustained at 5-year follow-up; 13% of patients had a preoperative DeMeester score of >50, and their median preoperative GERD-HRQL and RSI scores were 32 and 15.5, respectively. These were reduced to 0 at the most recent follow-up. There was a significant reduction in antacid use at all postoperative time points. Postoperative dilatation was necessary in 7.4% of patients, and the device was removed in 1.4%. Erosion occurred in no patients. MSA is safe and effective at reducing symptom burden and improving QOL scores in patients with both esophageal and laryngopharyngeal symptoms, including those with severe reflux.
Fewer transfusions are still more—red blood cell transfusions affect long-term mortality in cardiac surgery
Authors: Tang Mariann , Ravn Hanne Berg , Andreasen Jan Jesper , Greisen Jacob , Thomassen Sisse , Fabrin Anja , Jakobsen Carl-Johan
Published: March 2023

OBJECTIVES

Previous studies indicated higher long-term mortality after the transfusion of allogeneic red blood cells (RBC); newer recommendations emphasize lower transfusion rates. The consequences of the transfusion of RBCs in cardiac surgery are unclear because later studies focused on transfusion triggers and short-term outcomes. Reports on long-term complications after cardiac surgery are few.

MATERIAL AND METHODS

The mandatory Western Denmark Heart Registry was used to identify all adult cardiac operations performed in 4 centres from 2000 to 2019. Patients with multiple entries or previous cardiac operations, special/complex procedures, dying within 30 days and not eligible for follow-up were excluded.

RESULTS

A total of 32,581 adult cardiac operations performed in 4 centres from 2000 to 2019 were included. The Kaplan–Meier survival plot for low-risk patients undergoing simple cardiac operations showed a significantly lower 15-year survival (0.384 vs 0.661) of patients who received perioperative RBC transfusions [odds ratio 2.43 (confidence level 2.23–2.66)]. The risk decreased with increasing comorbidity or age. No difference was found in high-risk patients. The adjusted risk ratio after an RBC transfusion, including age, sex, comorbidity and surgery, was 1.62 (1.48–1.77).

CONCLUSIONS

Despite reduced transfusion rates, long-term follow-up on especially low-risk patients undergoing comparable cardiac operations still demonstrates substantially more deaths of patients receiving perioperative RBC transfusions. Even transfusion of 1–2 units is associated with increased long-term mortality.
Best ablation strategy in patients with premature ventricular contractions with multiple morphology: a single-centre experience
Authors: Mohanty Sanghamitra , Burkhardt John D , Di Biase Luigi , Mohanty Prasant , Shetty Sai Shishir , Gianni Carola , Della Rocca Domenico G , Baho Karim K , Morris Trevor , Mayedo Angel , MacDonald Bryan , Al-Ahmad Amin , Bassiouny Mohamed , Gallinghouse Gerald Joseph , Horton Rodney , Natale Andrea
Published: March 2023

Aims

This study aimed to examine the clinical benefits of targeted ablation of all Premature ventricular complex (PVC) morphologies vs. predominant PVC only.

Methods and results

A total of 171 consecutive patients with reduced left ventricular ejection fraction (LVEF) and ≥2 PVC morphology with high burden (>10%/day) undergoing their first ablation procedure were included in the analysis. At the initial procedure, prevalent PVC alone was ablated in the majority. However, at the redo, all PVC morphologies were targeted for ablation. : At the first procedure, 152 (89%) patients received ablation of the dominant PVC only. In the remaining 19 (11%) patients, all PVC morphologies were ablated. At two years, high PVC burden was detected in 89 (52%) patients. Repeat procedure was performed in 78 of 89, where all PVC morphologies were ablated. At 5 years after the repeat procedure, 71 (91%) had PVC burden of <5% [3.8 ± 1.1% vs. 15.4 ± 4.3% in successful vs. failed subjects (P < 0.001)]. In patients with low PVC burden after the initial procedure, LVEF improved from 37.5% to 41.6% [mean difference (MD): 3.39 ± 2.9%, P < 0.001], whereas a reduction in LVEF from 39.8% to 34.5% (MD: 6.45 ± 4.7%, P < 0.001) was recorded in patients with high PVC burden. One year after the repeat procedure, LVEF improved from 36.2% to 41.7% (MD: 5.5 ± 4.3%, P < 0.001) in patients with successful ablation.

Conclusion

In this observational series, ablation of all PVC morphologies was associated with significantly lower PVC burden and improvement of LVEF at long-term follow-up, compared with ablation of the dominant morphology only.
Should lethal arrhythmias in hypertrophic cardiomyopathy be predicted using non-electrophysiological methods?
Authors: Saumarez Richard , Silberbauer John , Scannell Jack , Pytkowski Mariusz , Behr Elijah R , Betts Timothy , Della Bella Paulo , Peters Nicholas S
Published: March 2023

While sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) is due to arrhythmias, the guidelines for prediction of SCD are based solely on non-electrophysiological methods. This study aims to stimulate thinking about whether the interests of patients with HCM are better served by using current, ‘risk factor’, methods of prediction or by further development of electrophysiological methods to determine arrhythmic risk. Five published predictive studies of SCD in HCM, which contain sufficient data to permit analysis, were analysed to compute receiver operating characteristics together with their confidence bounds to compare their formal prediction either by bootstrapping or Monte Carlo analysis. Four are based on clinical risk factors, one with additional MRI analysis, and were regarded as exemplars of the risk factor approach. The other used an electrophysiological method and directly compared this method to risk factors in the same patients. Prediction methods that use conventional clinical risk factors and MRI have low predictive capacities that will only detect 50–60% of patients at risk with a 15–30% false positive rate [area under the curve (AUC) = ∼0.7], while the electrophysiological method detects 90% of events with a 20% false positive rate (AUC = ∼0.89). Given improved understanding of complex arrhythmogenesis, arrhythmic SCD is likely to be more accurately predictable using electrophysiologically based approaches as opposed to current guidelines and should drive further development of electrophysiologically based methods.
Avoiding unnecessary ventricular pacing is associated with reduced incidence of heart failure hospitalizations and persistent atrial fibrillation in pacemaker patients
Authors: Arnold Martin , Richards Mark , D’Onofrio Antonio , Faulknier Brett , Gulizia Michele , Thakur Ranjan , Sakata Yasushi , Lin Wenjiao , Pollastrelli Annalisa , Grammatico Andrea , Auricchio Angelo , Boriani Giuseppe
Published: March 2023

Aims

In bradycardia patients treated with dual-chamber pacing, we aimed to evaluate whether pacing with atrioventricular (AV) delay management [AV hysteresis (AVH)], compared with standard pacing with fixed AV delays, reduces unnecessary ventricular pacing percentage (VPP) and is associated with better clinical outcomes. Main study endpoints were the incidence of heart failure hospitalizations (HFH), persistent atrial fibrillation (AF), and cardiac death.

Methods and results

Data from two identical prospective observational studies, BRADYCARE I in the USA and BRADYCARE II in Europe, Africa, and Asia, were pooled. Overall, 2592 patients (75 ± 10 years, 45.1% female, 50% with AVH) had complete clinical and device data at 1-year follow-up and were analysed. Primary pacing indication was sinus node disease (SND) in 1177 (45.4%), AV block (AVB) in 974 (37.6%), and other indications in 441 (17.0%) patients. Pacing with AVH, compared with standard pacing, was associated with a lower 1-year incidence of HFH [1.3% vs. 3.1%, relative risk reduction (RRR) 57.5%, P = 0.002] and of persistent AF (5.3% vs. 7.7%, RRR = 31.1%, P = 0.028). Cardiac mortality was not different between groups (1.0% vs. 1.4%, RRR = 27.8%, P = 0.366). Pacing with AVH, compared with standard pacing, was associated with a lower (P < 0.001) median VPP in all patients (7% vs. 75%), in SND (3% vs. 44%), in AVB (25% vs. 98%), and in patients with other pacing indications (3% vs. 47%).

Conclusion

Cardiac pacing with AV delay management via AVH is associated with reduced 1-year incidence of HFH and persistent AF, most likely due to a reduction in VPP compared to standard pacing.
Four billion years of microbial terpenome evolution
Authors: Hoshino Yosuke , Villanueva Laura
Published: March 2023

Terpenoids, also known as isoprenoids, are the largest and most diverse class of organic compounds in nature and are involved in many membrane-associated cellular processes, including membrane organization, electron transport chain, cell signaling, and phototrophy. Terpenoids are ancient compounds with their origin presumably before the last universal common ancestor. However, Bacteria and Archaea are known to possess two distinct terpenoid repertoires and utilize terpenoids differently. Most notably, archaea constitute their cellular membrane solely made of terpenoid-based phospholipids, contrary to the bacterial membrane that consists of fatty acid-based phospholipids. Thus, the composition of ancestral membranes at the beginning of cellular life and the diversification of terpenoids in early life remain enigmatic. This review addresses these key issues through comprehensive phylogenomic analyses of extant terpenoid biosynthesis enzymes in Bacteria and Archaea. We aim to infer the basal components of terpenoid biosynthesis machinery that have an ancient origin before the divergence of the two domains and shed light on the deep evolutionary connection between terpenoid biochemistry and early life.
The microbiology of Power-to-X applications
Authors: Logroño Washington , Kleinsteuber Sabine , Kretzschmar Jörg , Harnisch Falk , De Vrieze Jo , Nikolausz Marcell
Published: March 2023

Power-to-X (P2X) technologies will play a more important role in the conversion of electric power to storable energy carriers, commodity chemicals and even food and feed. Among the different P2X technologies, microbial components form cornerstones of individual process steps. This review comprehensively presents the state-of-the-art of different P2X technologies from a microbiological standpoint. We are focusing on microbial conversions of hydrogen from water electrolysis to methane, other chemicals and proteins. We present the microbial toolbox needed to gain access to these products of interest, assess its current status and research needs, and discuss potential future developments that are needed to turn todays P2X concepts into tomorrow's technologies.
Metformin extends the chronological lifespan of fission yeast by altering energy metabolism and stress resistance capacity
Authors: Şeylan Ceren , Tarhan Çağatay
Published: March 2023

The antiaging properties of metformin used for the treatment of type-2 diabetes mellitus have been studied extensively, but there is more to discover regarding underlying mechanisms. Here, we show that metformin significantly prolongs the chronological lifespan (CLS) of Schizosaccharomyces pombe through mechanisms similar to those observed in mammalian cells and other model organisms. While the presence of metformin in the medium caused an increase in carbohydrate consumption and ATP production, it reduced reactive oxygen species production and alleviate oxidative damage parameters such as lipid peroxidation and carbonylated proteins. We also tested whether the effect of metformin changed with the time it was added to the medium and observed that the lifespan-prolonging effect of metformin was related to the glucose concentration in the medium and did not prolong lifespan when added after glucose was completely depleted in the medium. On the other hand, cells inoculated in glucose-free medium containing metformin also showed extended lifespan suggesting that mechanisms other than that solely depend on glucose availability may be involved in extending the lifespan. These results suggest that metformin prolongs lifespan especially affecting energy metabolism and stress resistance capacity and that fission yeast can be effectively used when investigating the antiaging mechanisms of metformin.
An automated earthquake detection and characterization tool for rapid earthquake and tsunami response in Western Mediterranean
Authors: Menager Marine , Guilhem Trilla Aurélie , Delouis Bertrand
Published: March 2023

A method of moment tensor inversion with a grid search on the source location and time is presently considered by the French Tsunami Service Provider (TSP or CENALT in French) for rapid earthquake and tsunami warning in the western Mediterranean Sea and the North-East Atlantic Ocean. The approach follows the GRiD MT (Grid-based Real-time Determination of Moment Tensors) methodology already implemented in other regions. Here, we show developments made towards its implementation for moderate to large earthquakes in the Ibero–Maghreb region, which is prone to generate tsunamis in the western Mediterranean Sea. Results obtained for a dozen of events, contrasting in magnitudes, locations and focal mechanisms, validate the choices made for the inversion parameters (grid resolution, frequency band, velocity models, etc.). Their source solutions are compared to published solutions from seismological institutes including GFZ and USGS. Besides, we describe the special care needed for a correct real-time event detection analysis, and in particular for obtaining the most appropriate source solution out of the thousand ones explored by the method. Rapid GRiD MT solutions can in turn be used for rapid tsunami simulations run by the TSP operator.
Toward an experimental system for the examination of protein mannosylation in Actinobacteria
Authors: Saxena Hirak , Buenbrazo Nakita , Song Won-Yong , Li Connie , Brochu Denis , Robotham Anna , Ding Wen , Tessier Luc , Chen Rui , Kelly John , Wakarchuk Warren
Published: March 2023

The Actinobacterial species Cellulomonas fimi ATCC484 has long been known to secrete mannose-containing proteins, but a closer examination of glycoproteins associated with the cell has never been reported. Using ConA lectin chromatography and mass spectrometry, we have surveyed the cell-associated glycoproteome from C. fimi and collected detailed information on the glycosylation sites of 19 cell-associated glycoproteins. In addition, we have expressed a previously known C. fimi secreted cellulase, Celf_3184 (formerly CenA), a putative peptide prolyl-isomerase, Celf_2022, and a penicillin-binding protein, Celf_0189, in the mannosylation capable host, Corynebacterium glutamicum. We found that the glycosylation machinery in C. glutamicum was able to use the recombinant C. fimi proteins as substrates and that the glycosylation matched closely that found in the native proteins when expressed in C. fimi. We are pursuing this observation as a prelude to dissecting the biosynthetic machinery and biological consequences of this protein mannosylation.
Antibiotic consumption trends in Ghana: analysis of six-years pharmacy issue data from a secondary healthcare facility
Authors: Labi Appiah-Korang , Kartey Bridget S , Hedidor George Kwesi , Nuertey Benjamin Demah , Kodjoe Elsie , Vanderpuije Leslie No , Obeng-Nkrumah Noah
Published: March 2023

Background

Surveillance of hospital antibiotic consumption provides data to inform corrective action and for monitoring antimicrobial stewardship activities. This study described antibiotic consumption patterns from 2016 through 2021 at a secondary healthcare facility in Ghana.

Methods

Using the WHO methodology for surveillance of antimicrobial consumption in hospitals, we analysed a 6-year pharmacy issue data at the Eastern Regional Hospital. We report on the defined daily dose (DDD) per 100 patients, types of antibiotics consumed according to Anatomic Therapeutic Classification (ATC), WHO AWaRe classification; trends in antibiotic consumption and expenditure per DDD of antibiotics consumed.

Results

Over the period, the mean (±standard deviation) antibiotic consumption rate was 256.7 ± 33 DDD/100 patients per year. A linear regression model showed an insignificant decreasing trend in antibiotic consumption (coefficient for time –0.561; P = 0.247). The top three consumed antibiotics in DDD/100 patients at ATC level 5 were amoxicillin-clavulanate (n = 372.6), cefuroxime (n = 287.4) and sulfamethoxazole-trimethoprim (n = 145.8). The yearly Access-to-Watch ratio decreased from 2.4 in 2016 to 1.2 in 2021. The mean yearly cost of antibiotics was $394 206 ± 57 618 US dollars. The top three antibiotics consumed in terms of cost were clindamycin $718 366.3, amoxicillin-clavulanate $650 928.3 and ceftriaxone $283 648.5.

Conclusion

This study showed a sturdy rate of antibiotic consumption over the 6-year period with a year-on-year decrease in the Access-to-Watch antibiotic ratio. Data from pharmacy drug issues offer an opportunity to conduct antibiotic consumption surveillance at the hospital and national level in Ghana.
Dietary inflammatory and insulinemic potential, risk of hepatocellular carcinoma, and chronic liver disease mortality
Authors: Long Lu , Liu Xing , Petrick Jessica , Liu Wanqing , Lee Jeffrey K , Liao Linda , Lai Michelle J , Yang Wanshui , Libermann Towia A , Roberts Lewis R , McGlynn Katherine A , Tabung Fred K , Zhang Xuehong
Published: March 2023

Background

Diet modulates inflammation and insulin response and may be an important modifiable factor in the primary prevention of hepatocellular carcinoma (HCC) and chronic liver disease (CLD). We developed the empirical dietary inflammatory pattern (EDIP) and empirical dietary index for hyperinsulinemia (EDIH) scores to assess the inflammatory and insulinemic potentials of diet. We prospectively examined the associations of EDIP and EDIH at baseline with the following HCC risk and CLD mortality.

Design

We followed 485 931 individuals in the National Institutes of Health–American Association of Retired Persons Diet and Health Study since 1995. Cox proportional hazards regression was used to calculate multivariable hazard ratios (HRs) and 95% confidence intervals (CIs).

Results

We confirmed 635 incident HCC cases and 993 CLD deaths. Participants in the highest compared with those in the lowest EDIP quartile had a 1.35 times higher risk of developing HCC (95% CI = 1.08 to 1.70, Ptrend = .0005) and a 1.70 times higher CLD mortality (95% CI = 1.41 to 2.04, Ptrend < .0001). For the same comparison, participants with the highest EDIH were at increased risk of HCC (HR = 1.53, 95% CI = 1.20 to 1.95, Ptrend = .0004) and CLD mortality (HR = 1.72, 95% CI = 1.42 to 2.01, Ptrend < .0001). Similar positive associations of scores with HCC risk and CLD mortality were observed for both women and men. Moreover, individuals in both the highest EDIP and EDIH tertiles had a 92% increased HCC risk (95% CI = 1.43 to 2.58) and 98% increased CLD mortality (95% CI = 1.27 to 3.08) compared with those in both lowest tertiles.

Conclusions

Our findings suggest that inflammation and hyperinsulinemia are potential mechanisms linking diet to HCC development and CLD mortality.
Accuracy and Probabilism in Infinite Domains
Authors: Nielsen Michael
Published: March 2023

The best accuracy arguments for probabilism apply only to credence functions with finite domains, that is, credence functions that assign credence to at most finitely many propositions. This is a significant limitation. It reveals that the support for the accuracy-first programme in epistemology is a lot weaker than it seems at first glance, and it means that accuracy arguments cannot yet accomplish everything that their competitors, the pragmatic (Dutch book) arguments, can. In this paper, I investigate the extent to which this limitation can be overcome. Building on the best arguments in finite domains, I present two accuracy arguments for probabilism that are perfectly general—they apply to credence functions with arbitrary domains. I then discuss how the arguments’ premisses can be challenged. We will see that it is particularly difficult to characterize admissible accuracy measures in infinite domains.
Observational constraints of an anisotropic boost due to the projection effects using redMaPPer clusters
Authors: Sunayama Tomomi
Published: March 2023

Optical clusters identified from red-sequence galaxies suffer from projection effects, where interloper galaxies along the line of sight to a cluster are mistaken as genuine members of the cluster. In the previous study, we found that the projection effects cause the boost on the amplitudes of clustering and lensing on large scale compared to the expected amplitudes in the absence of any projection effects. These boosts are caused by preferential selections of filamentary structure aligned to the line of sight due to distance uncertainties in photometric surveys. We model the projection effects with two simple assumptions and develop a novel method to quantify the size of the boost using cluster-galaxy cross-correlation functions. We validate our method using mock cluster catalogues built from cosmological N-body simulations and find that we can obtain unbiased constraints on the boost parameter with our model. We then apply our analysis on the SDSS redMaPPer clusters and find that the size of the boost is roughly 20 per cent for all the richness bins except the cluster sample with the richness bin λ ∈ [30, 40]. This is the first study to constrain the boost parameter independent from cluster cosmology studies and provides a self-consistency test for the projection effects.
A photoelectric study of the eclipsing binary EG Serpentis
Authors: Thurman Glenn M
Published: March 2023

A ubvy photoelectric study of the early A-type, detached eclipsing binary EG Serpentis (EG Ser) has been undertaken at Mount Laguna Observatory. Simultaneous observation on two telescopes has been employed for the first time at the observatory. Approximately 2000 standardized differential magnitudes are presented along with standardized colours and V magnitudes of the EG Ser field. A new ephemeris is determined that indicates a small positive displacement of secondary eclipse. The photometric elements are solved for using the NDE model, and the presence of a small, but non-zero, orbital eccentricity is confirmed. The photometry is combined with published spectroscopy to obtain absolute parameters for the system. The colour excess of and distance to the binary are determined. An approximate age is estimated. The results are compared with the only other published solution (of about the same vintage) and recent light-curve solutions by the author of this study.
Formation of supermassive stars in the first star clusters
Authors: Reinoso Bastián , Klessen Ralf S , Schleicher Dominik , Glover Simon C O , Solar P
Published: March 2023

The formation of supermassive stars is believed to be an essential intermediate step for the formation of the massive black hole seeds that become the supermassive black holes powering the quasars observed in the early Universe. Numerical simulations have shown that supermassive stars can form in atomic-cooling haloes when protostars reach accretion rates higher than ∼10−2 M⊙ yr−1 and fragmentation is suppressed on pc scales. It is, however, still uncertain if a supermassive star still emerges when fragmentation occurs at smaller scales and a cluster of stars is formed instead. In this work, we explore the problem of massive object formation due to the interplay of collisions and accretion in star clusters at low metallicity. We model a small embedded cluster of accreting protostars following subparsec scale fragmentation during the collapse of a primordial gas cloud, and follow its evolution by performing N-body plus hydrodynamical simulations. Our results show that supermassive stars with 103 and 104 M⊙ are always formed due to the interplay of collisions and accretion, and in some cases these objects are part of a binary system. The resulting supermassive star is surrounded by tens of smaller stars with typical masses in the range 1–100 M⊙.
The physical origin of supercompetitive accretion during the formation of the first supermassive black holes
Authors: Schleicher Dominik R G , Reinoso Bastián , Klessen Ralf S
Published: March 2023

Numerical simulations have shown the occurrence of a scenario termed ‘supercompetitive accretion’, a term that describes a situation where only the central few objects grow supermassive while a larger number of stars compete for the reservoir, with significant accretion flows of ≳0.1 M⊙ yr−1. This scenario particularly implies that the presence of fragmentation will not necessarily impeed the formation of a central massive object. We, here, explore this phenomenon using analytical estimates for growth via collisions and accretion, considering accretion due to self-gravity as well as Bondi–Hoyle accretion. Particularly, we explore under what conditions the accretion on to the central massive object breaks down, and derive a criterion that depends on the mass of the most massive object and the mass in fragments. For compact clusters with sizes about 0.1 pc, we further find that the mass growth by collisions is comparable to the growth via accretion. Our results are validated through the comparison with numerical simulations, and we overall conclude that supercompetitive accretion is a valid mechanism for the formation of very massive objects in the early Universe.
The effects of time-variable absorption due to gamma-ray bursts in active galactic nucleus accretion discs
Authors: Ray Michael , Lazzati Davide , Perna Rosalba
Published: March 2023

Both long and short gamma-ray bursts (GRBs) are expected to occur in the dense environments of active galactic nucleus (AGN) accretion discs. As these bursts propagate through the discs they live in, they photoionize the medium causing time-dependent opacity that results in transients with unique spectral evolution. In this paper, we use a line-of-sight radiation transfer code coupling metal and dust evolution to simulate the time-dependent absorption that occurs in the case of both long and short GRBs. Through these simulations, we investigate the parameter space in which dense environments leave a potentially observable imprint on the bursts. Our numerical investigation reveals that time-dependent spectral evolution is expected for central supermassive black hole masses between 105 and 5 × 107 solar masses in the case of long GRBs, and between 104 and 107 solar masses in the case of short GRBs. Our findings can lead to the identification of bursts exploding in AGN disc environments through their unique spectral evolution coupled with a central location. In addition, the study of the time-dependent evolution would allow for studying the disc structure, once the identification with an AGN has been established. Finally, our findings lead to insight into whether GRBs contribute to the AGN emission, and which kind, thus helping to answer the question of whether GRBs can be the cause of some of the as-of-yet unexplained AGN time variability.
Exciting the transit timing variation phases of resonant sub-Neptunes
Authors: Choksi Nick , Chiang Eugene
Published: March 2023

There are excesses of sub-Neptunes just wide of period commensurabilities like the 3:2 and 2:1, and corresponding deficits narrow of them. Any theory that explains this period ratio structure must also explain the strong transit timing variations (TTVs) observed near resonance. Besides an amplitude and a period, a sinusoidal TTV has a phase. Often overlooked, TTV phases are effectively integration constants, encoding information about initial conditions or the environment. Many TTVs near resonance exhibit non-zero phases. This observation is surprising because dissipative processes that capture planets into resonance also damp TTV phases to zero. We show how both the period ratio structure and the non-zero TTV phases can be reproduced if pairs of sub-Neptunes capture into resonance in a gas disc while accompanied by a third eccentric non-resonant body. Convergent migration and eccentricity damping by the disc drives pairs to orbital period ratios wide of commensurability; then, after the disc clears, secular forcing by the third body phase shifts the TTVs. The scenario predicts that resonant planets are apsidally aligned and possess eccentricities up to an order of magnitude larger than previously thought.
Photometric study of the late-time near-infrared plateau in Type Ia supernovae
Authors: Deckers M , Graur O , Maguire K , Shingles L , Brennan S J , Anderson J P , Burke J , Chen T-W , Galbany L , Grayling M J P , Gutiérrez C P , Harvey L , Hiramatsu D , Howell D A , Inserra C , Killestein T , McCully C , Müller-Bravo T E , Nicholl M , Newsome M , Padilla Gonzalez E , Pellegrino C , Terreran G , Terwel J H , Toy M , Young D R
Published: March 2023

We present an in-depth study of the late-time near-infrared plateau in Type Ia supernovae (SNe Ia), which occurs between 70 and 500 d. We double the existing sample of SNe Ia observed during the late-time near-infrared plateau with new observations taken with the Hubble Space Telescope, Gemini, New Technology Telescope, the 3.5-m Calar Alto Telescope, and the Nordic Optical Telescope. Our sample consists of 24 nearby SNe Ia at redshift < 0.025. We are able to confirm that no plateau exists in the Ks band for most normal SNe Ia. SNe Ia with broader optical light curves at peak tend to have a higher average brightness on the plateau in J and H, most likely due to a shallower decline in the preceding 100 d. SNe Ia that are more luminous at peak also show a steeper decline during the plateau phase in H. We compare our data to state-of-the-art radiative transfer models of nebular SNe Ia in the near-infrared. We find good agreement with the sub-Mch model that has reduced non-thermal ionization rates, but no physical justification for reducing these rates has yet been proposed. An analysis of the spectral evolution during the plateau demonstrates that the ratio of [Fe ii] to [Fe iii] contribution in a near-infrared filter determines the light curve evolution in said filter. We find that overluminous SNe decline slower during the plateau than expected from the trend seen for normal SNe Ia.
New EoR power spectrum limits from MWA Phase II using the delay spectrum method and novel systematic rejection
Authors: Kolopanis Matthew , Pober Jonathan C , Jacobs Daniel C , McGraw Samantha
Published: March 2023

We present an analysis of Epoch of Reionization (EoR) data from Phase II of the Murchison Widefield Array using the simpleds delay spectrum pipeline. Prior work analysed the same observations using the fhd/εppsilon imaging pipeline, and so the present analysis represents the first time that both principal types of 21 cm cosmology power spectrum estimation approaches have been applied to the same data set. Our limits on the 21 cm power spectrum amplitude span a range in k space of $|k| \lt 1 \, h_{100}\, {\rm Mpc}^{-1}$ with a lowest measurement of Δ2(k) ≤ 4.58 × 103 mK2 at $k = 0.190\, h_{100}\, \rm {Mpc}^{-1}$ and z = 7.14. In order to achieve these limits, we need to mitigate a previously unidentified common mode systematic in the data set. If not accounted for, this systematic introduces an overall negative bias that can make foreground contaminated measurements appear as stringent, noise-limited constraints on the 21 cm signal amplitude. The identification of this systematic highlights the risk in modelling systematics as positive-definite contributions to the power spectrum and in ‘conservatively’ interpreting all measurements as upper limits.
Investigation of treatment continuity, usefulness, and nocebo effect in switching from the original etanercept to its biosimilar in patients with rheumatoid arthritis: A JET observational study in Japanese clinical practice
Authors: Matsubara Tsukasa , Katayama Kou , Sagawa Akira , Yoshida Masaaki , Mitsuka Takeshi , Hashimoto Keisuke , Izumihara Tomomaro , Kondo Masakazu , Izumiyama Tomomasa , Miyake Nobumasa , Yoshii Ichiro , Oribe Motohiro , Momohara Shigeki , Funahashi Keiko
Published: March 2023

Objectives

To assess the usefulness and onset of nocebo effects after switching from the original etanercept (ETN) to a biosimilar (BS) in routine clinical practice at rheumatology clinics in Japan (13 sites).

Methods

A total of 165 patients (87.0% women, age = 57.88 ± 15.07 years, and disease duration = 10.32 ± 7.71 years), whose low disease activity was maintained with the original ETN for ≥12 weeks, and who agreed to switch treatment to its BS, were included. The end-points were disease activity score 28 (DAS28)-C-reactive protein and DAS28-erythrocyte sedimentation rate.

Results

No significant difference was observed between the changes in DAS28-C-reactive protein and DAS28-erythrocyte sedimentation rate >12 weeks before switching and >12 weeks after switching (P = 0.132 and 0.334, respectively). The treatment continuation rate during the 52 weeks after switching to BS was 97.3%. During this period, BS was discontinued in only four patients, and no nocebo effects were suspected in these four patients.

Conclusion

Switching from ETN to BS was effective even in routine clinical practice at rheumatology clinics in Japan, and no nocebo effects were observed. Sufficient explanations to patients by rheumatologists and the additional payment for drug costs between patients at hospital visits effectively improved the continuation rate without any nocebo effect.
DFT and TD-DFT study of Optical and Electronic Properties of new donor–acceptor–donor (D–A–D′) monomers for polymer solar cells
Authors: Lyakurwa Melchizedek , Numbury Surendra Babu
Published: March 2023

The Density Functional Theory (DFT) and time-dependent-DFT method with Becke’s three-parameter Lee-Yang–Parr functional approach at a basis set of 6-311G was used to analyze the ground state and excited state properties of newly designed donor–acceptor–donor (D–A–D′) donor molecules based on triphenylamine and carbazole as donor units and benzothiadiazole and its derivatives as acceptor units to make a total of nine potential monomers. The energies associated with highest occupied molecular orbital, lowest occupied molecular orbital, energy gap (Eg), electron excitation (Eopt), exciton binding (Eb) and open-circuit voltage (Voc) were calculated, and the simulated absorption spectra in both gas and chlorobenzene solvent were plotted. The outcomes of replacing the acceptor building unit and substituting the donor units to tailor the optoelectronic properties of the designed monomers were discussed. The monomer molecules A7, A8 and A9 are suitable for [6,6]-phenyl-C61-butyric acid methyl ester because of their small Eg, Eopt, Eb and, more importantly, large Voc values. Suggesting changing the acceptor unit and substituting the donor units of the D–A–D′ seem to be an excellent approach to tailoring the optoelectronic properties of the molecules.
Drug decriminalization: The importance of policy change for the health and wellbeing of children and youth in Canada
Authors: Holland Alyson , Etches Selene , Gander Sarah
Published: March 2023

The criminalization of drug use and possession has demonstrable harms on the health of children and youth, with disproportionate effects on Black people, Indigenous people, people from other racially oppressed communities, and people living in poverty. Drug decriminalization, by separating personal possession and use of drugs from the criminal justice system, allows for a health-based approach to drug policy. Paediatricians are well-positioned to advocate for policies within a decriminalization framework to prioritize the physical and mental health of children and youth.
Image-Based Quantification of Arabidopsis thaliana Stomatal Aperture from Leaf Images
Authors: Takagi Momoko , Hirata Rikako , Aihara Yusuke , Hayashi Yuki , Mizutani-Aihara Miya , Ando Eigo , Yoshimura-Kono Megumi , Tomiyama Masakazu , Kinoshita Toshinori , Mine Akira , Toda Yosuke
Published: March 2023

The quantification of stomatal pore size has long been a fundamental approach to understand the physiological response of plants in the context of environmental adaptation. Automation of such methodologies not only alleviates human labor and bias but also realizes new experimental research methods through massive analysis. Here, we present an image analysis pipeline that automatically quantifies stomatal aperture of Arabidopsis thaliana leaves from bright-field microscopy images containing mesophyll tissue as noisy backgrounds. By combining a You Only Look Once X–based stomatal detection submodule and a U-Net-based pore segmentation submodule, we achieved a mean average precision with an intersection of union (IoU) threshold of 50% value of 0.875 (stomata detection performance) and an IoU of 0.745 (pore segmentation performance) against images of leaf discs taken with a bright-field microscope. Moreover, we designed a portable imaging device that allows easy acquisition of stomatal images from detached/undetached intact leaves on-site. We demonstrated that this device in combination with fine-tuned models of the pipeline we generated here provides robust measurements that can substitute for manual measurement of stomatal responses against pathogen inoculation. Utilization of our hardware and pipeline for automated stomatal aperture measurements is expected to accelerate research on stomatal biology of model dicots.
Technology and Tool Development for BACPAC: Qualitative and Quantitative Analysis of Accelerated Lumbar Spine MRI with Deep-Learning Based Image Reconstruction at 3T
Authors: Han Misung , Bahroos Emma , Hess Madeline E , Chin Cynthia T , Gao Kenneth T , Shin David D , Villanueva-Meyer Javier E , Link Thomas M , Pedoia Valentina , Majumdar Sharmila
Published: March 2023

Objectives

To evaluate whether combining fast acquisitions with deep-learning reconstruction can provide diagnostically useful images and quantitative assessment comparable to standard-of-care acquisitions for lumbar spine magnetic resonance imaging (MRI).

Methods

Eighteen patients were imaged with both standard protocol and fast protocol using reduced signal averages, each protocol including sagittal fat-suppressed T2-weighted, sagittal T1-weighted, and axial T2-weighted 2D fast spin-echo sequences. Fast-acquisition data was additionally reconstructed using vendor-supplied deep-learning reconstruction with three different noise reduction factors. For qualitative analysis, standard images as well as fast images with and without deep-learning reconstruction were graded by three radiologists on five different categories. For quantitative analysis, convolutional neural networks were applied to sagittal T1-weighted images to segment intervertebral discs and vertebral bodies, and disc heights and vertebral body volumes were derived.

Results

Based on noninferiority testing on qualitative scores, fast images without deep-learning reconstruction were inferior to standard images for most categories. However, deep-learning reconstruction improved the average scores, and noninferiority was observed over 24 out of 45 comparisons (all with sagittal T2-weighted images while 4/5 comparisons with sagittal T1-weighted and axial T2-weighted images). Interobserver variability increased with 50 and 75% noise reduction factors. Deep-learning reconstructed fast images with 50% and 75% noise reduction factors had comparable disc heights and vertebral body volumes to standard images (r2≥ 0.86 for disc heights and r2≥ 0.98 for vertebral body volumes).

Conclusions

This study demonstrated that deep-learning-reconstructed fast-acquisition images have the potential to provide noninferior image quality and comparable quantitative assessment to standard clinical images.
Course and predictors of work productivity in gout — results from the NOR-Gout longitudinal 2-year treat-to-target study
Authors: Uhlig Till , Karoliussen Lars F , Sexton Joe , Provan Sella Aarrestad , Kvien Tore K , Haavardsholm Espen A , Hammer Hilde Berner
Published: March 2023

Objectives

In patients with gout there is a lack of longitudinal studies on the course of work productivity. We explored longitudinal changes in and predictors of work productivity over 2 years.

Methods

Patients in the NOR-Gout observational study with a recent gout flare and serum urate (sUA) >360 µmol/l attended tight-control visits during escalating urate lowering therapy according to a treat-to-target strategy. From the Work Productivity and Activity Impairment (WPAI) questionnaire, scores for work productivity and activity impairment were assessed over 2 years together with the Beliefs about Medicines Questionnaire and a variety of demographic and clinical variables.

Results

At baseline patients had a mean age of 56.4 years and 95% were males. WPAI scores at baseline were 5.0% work missed (absenteeism), 19.1% work impairment (presenteeism), 21.4% overall work impairment and 32.1% activity impairment. Work productivity and activity impairment improved during the first months, and remained stable at 1 and 2 years. Comorbidities were not cross-sectionally associated with WPAI scores at baseline, but predicted worse work impairment and activity impairment at year 1. The Beliefs about Medicines Questionnaire subscale with concerns about medicines at baseline independently predicted worse overall work impairment and worse activity impairment at year 1.

Conclusions

In patients with gout who were intensively treated to the sUA target, work productivity and activity impairment were largely unchanged and at 1 year predicted by comorbidities and patient concerns about medication.
Etanercept originator versus etanercept biosimilar for the treatment of rheumatoid arthritis as a first biologic: results from the BSRBR-RA
Authors: Kearsley-Fleet Lianne , Rokad Aasiyah , Tsoi Man-Fung , Zhao Sizheng Steven , Lunt Mark , Watson Kath D ,   BSRBR-RA Contributors Group, Hyrich Kimme L
Published: March 2023

Objectives

Etanercept biosimilars show comparable efficacy to their originators among biologic-naïve patients with RA in randomized controlled trials. Nationwide guidelines have obligated prescribing of etanercept biosimilars from 2016, resulting in significant cost savings. This analysis aimed to compare the effectiveness of etanercept originator vs etanercept biosimilar amongst biologic-naïve RA patients treated in routine clinical practice in the UK.

Methods

Biologic-naïve RA patients starting etanercept in the British Society for Rheumatology Biologics Register in Rhematoid Arthritis (BSRBR-RA) cohort study from 2010 were included. Data collected at start of therapy includes patient demographics and disease activity. Follow-up data includes changes in disease activity and anti-rheumatic therapy. Six- and 12-month primary outcomes include DAS for 28-joints (DAS28) remission, EULAR response and minimal clinically important difference in function. Etanercept drug survival was assessed using Kaplan–Meier and Cox regression, including reasons for treatment withdrawal. Multiple imputation accounted for missing data. Propensity-decile adjustment was used to account for confounding by indication.

Results

A total of 1806 biologic-naïve RA patients started etanercept: 1009 originator, 797 biosimilar. At 6 and 12 months, the proportion of patients achieving DAS28 remission and EULAR response were similar between treatments. During follow-up, 19% of originator patients switched onto etanercept biosimilar. Patients were censored at time of switch. Patients on originator were no more likely to stop therapy vs biosimilar; 71% of originator and 76% of biosimilar patients remained on therapy at 1 year.

Conclusions

In one of the largest analyses of patients with RA, biologic-naïve RA patients treated with etanercept originator showed similar outcomes vs biosimilar using real-world data. Drug survival, and disease activity after 6 and 12 months of therapy, was similar between cohorts.