bluuebunny/crossref_metadata_2025 huggingface dataset:
Single-stapling technique versus hand-sewn anastomosis in inter-sphincteric resection with transanal total mesorectal excision (Super SST): protocol for a multicentre randomized clinical trial
Authors: Kitaguchi Daichi , Wakabayashi Masashi , Hasegawa Hiro , Ando Koji , Ikeda Koji , Tsukada Yuichiro , Nishizawa Yuji , Ito Masaaki
Published: January 2023

Background

Currently, hand-sewn anastomosis is the standard procedure for inter-sphincteric resection (ISR); however, distal purse-string suturing during transanal total mesorectal excision (TaTME) has allowed a single-stapling technique (SST). Although it was originally intended for cases requiring anastomosis of 2 cm or more above the anorectal junction (ARJ), SST could be safely performed in ISR. The aim of this trial is to determine the superiority of SST over hand-sewn anastomosis in ISR with TaTME.

Methods

The Super SST trial is a multicentre randomized clinical trial comparing stapled and hand-sewn anastomoses in ISR with TaTME. The trial will recruit patients scheduled for TaTME with anastomosis below the ARJ, who will be allocated 1:1 to receive either hand-sewn or stapled anastomosis. The primary endpoint is anastomosis-related complications within 30 postoperative days. Secondary endpoints include all early and late complications, operating time, reoperation, mortality rate, length of postoperative hospital stay, readmission, incidence of anal pain and rectal mucosal prolapse, length of temporary stoma retention, the proportion of patients with a temporary stoma at 1 year after surgery, and anorectal function at 1 year after surgery.

Conclusion

This trial will provide important clinical insights for new and promising anastomotic options for patients with very low rectal cancer.

Registration number: UMIN000047818 (https://www.umin.ac.jp/ctr/index-j.htme).
Randomized double-blind placebo-controlled clinical trial to evaluate the effect of a mixture of probiotic strains on symptom severity and use of corticosteroids in children and adolescents with atopic dermatitis
Authors: Feíto-Rodríguez Marta , Ramírez-Boscà Ana , Vidal-Asensi Santiago , Fernández-Nieto Diego , Ros-Cervera Gonzalo , Alonso-Usero Vicent , Prieto-Merino David , Núñez-Delegido Eva , Ruzafa-Costas Beatriz , Sánchez-Pellicer Pedro , Genovés Salvador , Navarro-López Vicente
Published: January 2023

Background

The intestinal microbiota is altered in patients with atopic dermatitis (AD) when compared with those of the healthy population. Some interventions with specific probiotic preparations already demonstrate a change in composition of this microbiota accompanied by improvement in the disease.

Objectives

This research work was designed to evaluate clinical efficacy of the probiotic preparation, and to measure the effect of the intervention on the total dose of corticosteroids administered to subjects.

Methods

This double-blind, randomized, placebo-controlled clinical trial including 70 participants with AD aged 4–17 years was designed to evaluate the clinical effect, compared with placebo, of a probiotic mixture of Bifidobacterium lactis, Bifidobacterium longum and Lactobacillus casei at a total daily consumption of 1 × 109 colony-forming units per capsule, over 12 weeks. After randomization and exclusion, 35 patients were allocated to probiotic and 35 to placebo. Clinical variables analysed were SCORAD (SCORing of Atopic Dermatitis) and Investigator Global Assessment (IGA) indices; effect on the amount of topical corticosteroids used; and assessment of safety.

Results

Mean SCORAD index at 12 weeks showed a statistically significant difference of −5.43 (95% confidence interval −10.65 to −0.21) between probiotic (SCORAD 13.52) and placebo groups (SCORAD 18.96); P = 0.04. Comparison between groups showed a statistically significant difference in the number of patients with IGA score improvement over the 12-week intervention: 29 of 32 (90.5%) in the probiotic group vs. 17 of 30 (56.7%) in the placebo group (P < 0.002). A comparison between groups of the proportions of days using corticosteroids and the total dose (g) of corticosteroids between baseline and end of study showed no significant difference, but between weeks 6 and 12 there was a statistically significant reduction in the probiotic group when compared with the placebo group in both variables. Numbers of adverse events were similar in both groups of treatment.

Conclusions

The probiotic mix used in this clinical trial demonstrated efficacy on the change in activity index of AD compared with placebo. Furthermore, the total number of days and total amount of topical corticosteroids required by participants in the probiotic group showed a significant reduction compared with placebo between 6 and 12 weeks.
Memorizing poetry
Authors: Culler Jonathan
Published: January 2023

Before the mid-twentieth century, pedagogy in many countries involved a considerable amount of memorization, perhaps especially in engagements with literature. But after World War II, the practice of memorization and public recitation virtually disappeared in American schools, generally replaced by a practice of analysis in which the poem is experienced principally as an object of interpretation. Here, Jonathan Culler describes the undergraduate course ‘Major Poets’, taught by him for many years at Cornell University. For each of the poets studied (including Shakespeare, Pope, Keats, and Dickinson), the students were asked to complete a variety of exercises, one of which was to memorize and recite a poem of at least 12 lines. In doing so, the highly patterned language of the poem was presented not as something to be interpreted, but as a discourse to be repeated, performed, and appreciated in other ways.
The Evolution of Databases in the Age of Targeted Sanctions
Authors: Portela Clara , Charron Andrea
Published: January 2023

Databases constitute key research tools in sanctions scholarship. Over the past few years, we have witnessed a proliferation of sanctions databases: while only a single dataset was available until 2009, this number had increased to five by 2020; thus, the choice has more than doubled in less than a decade. This essay assesses the evolution observed. It reviews the five major datasets, comparing some of their basic choices, and evaluates them along two dimensions: the extent to which they capture targeted sanctions and the degree to which they brought innovations to the subfield. We find that targeted sanctions are not adequately reflected in databases, which remain state-centric in their approach. We conclude that the crafting of new databases does not entail an incremental refinement in which each iteration renders its predecessors obsolete. Rather, the evolution observed has resulted in a diverse set of options with different emphases. We nevertheless observe that a trend toward innovation has yielded to one toward consolidation, more focused on enlarging the empirical testing ground than in innovating. We conclude by discussing implications for the development of sanctions scholarship.
Glyphosate-based herbicide use affects individual microbial taxa in strawberry endosphere but not the microbial community composition
Authors: Mathew Suni Anie , Fuchs Benjamin , Nissinen Riitta , Helander Marjo , Puigbò Pere , Saikkonen Kari , Muola Anne
Published: January 2023

Aims

In a field study, the effects of treatments of glyphosate-based herbicides (GBHs) in soil, alone and in combination with phosphate fertilizer, were examined on the performance and endophytic microbiota of garden strawberry.

Methods and results

The root and leaf endophytic microbiota of garden strawberries grown in GBH-treated and untreated soil, with and without phosphate fertilizer, were analyzed. Next, bioinformatics analysis on the type of 5-enolpyruvylshikimate-3-phosphate synthase enzyme was conducted to assess the potential sensitivity of strawberry-associated bacteria and fungi to glyphosate, and to compare the results with field observations. GBH treatments altered the abundance and/or frequency of several operational taxonomic units (OTUs), especially those of root-associated fungi and bacteria. These changes were partly related to their sensitivity to glyphosate. Still, GBH treatments did not shape the overall community structure of strawberry microbiota or affect plant performance. Phosphate fertilizer increased the abundance of both glyphosate-resistant and glyphosate-sensitive bacterial OTUs, regardless of the GBH treatments.

Conclusions

These findings demonstrate that although the overall community structure of strawberry endophytic microbes is not affected by GBH use, some individual taxa are.
Plasma protein levels of young healthy pigs as indicators of disease resilience
Authors: Chen Yulu , Lonergan Steven , Lim Kyu-Sang , Cheng Jian , Putz Austin M , Dyck Michael K , Canada PigGen , Fortin Frederic , Harding John C S , Plastow Graham S , Dekkers Jack C M
Published: January 2023

Selection for disease resilience, which refers to the ability of an animal to maintain performance when exposed to disease, can reduce the impact of infectious diseases. However, direct selection for disease resilience is challenging because nucleus herds must maintain a high health status. A possible solution is indirect selection of indicators of disease resilience. To search for such indicators, we conducted phenotypic and genetic quantitative analyses of the abundances of 377 proteins in plasma samples from 912 young and visually healthy pigs and their relationships with performance and subsequent disease resilience after natural exposure to a polymicrobial disease challenge. Abundances of 100 proteins were significantly heritable (false discovery rate (FDR) <0.10). The abundance of some proteins was or tended to be genetically correlated (rg) with disease resilience, including complement system proteins (rg = −0.24, FDR = 0.001) and IgG heavy chain proteins (rg = −0.68, FDR = 0.22). Gene set enrichment analyses (FDR < 0.2) based on phenotypic and genetic associations of protein abundances with subsequent disease resilience revealed many pathways related to the immune system that were unfavorably associated with subsequent disease resilience, especially the innate immune system. It was not possible to determine whether the observed levels of these proteins reflected baseline levels in these young and visually healthy pigs or were the result of a response to environmental disturbances that the pigs were exposed to before sample collection. Nevertheless, results show that, under these conditions, the abundance of proteins in some immune-related pathways can be used as phenotypic and genetic predictors of disease resilience and have the potential for use in pig breeding and management.
The Socioecology of Parental Adjustment to Pediatric Cancer: The Roles of Individual and Neighborhood Socioeconomic Status in Parental Social Support and Depressive Symptoms
Authors: Davidson Savannah , Contreras Janie , Santamaría Claudia Reino , Alba-Suarez Juliana , Patel Puja , Greenspahn Emily , Boucher Lori , Rodriguez Erin M
Published: January 2023

Objective

Parents of children with cancer are at risk for depressive symptoms, and previous research has linked their level of distress to various demographic, social, and economic factors. However, little research has examined associations between parental depressive symptoms and multiple socioecological factors at once. The current study examined how socioeconomic status (SES) at the individual and neighborhood level is related to parental depressive symptoms and social support satisfaction in Latinx and non-Latinx parents of children recently diagnosed with cancer, and whether social support satisfaction mediated associations between SES and depressive symptoms.

Methods

Parents (N = 115; 82% female; 30% Latinx) completed questionnaires reporting their demographic information, social support satisfaction, and depressive symptoms. Neighborhood SES was coded by block group level based on participants’ home addresses.

Results

Individual, but not neighborhood, SES was positively associated with social support satisfaction, and higher social support satisfaction was associated with lower depressive symptoms. There was a significant indirect effect of individual (but not neighborhood) SES on depressive symptoms through social support satisfaction. Latinx parents reported lower individual SES, but not lower social support satisfaction or depressive symptoms than non-Latinx parents.

Conclusions

These results highlight the important role of social support in the adjustment of parents who have a child with pediatric cancer. Findings suggest that families may benefit from services that target multiple levels of their social ecology.
Religion Pays: The Business of Art Industry Entrepreneurs and Splendour in the Spaces of Nineteenth-Century Irish Catholicism
Authors: McGee Caroline M
Published: January 2023

During the nineteenth century legislative reforms and religious revival in Ireland brought about significant change in the practice and position of Catholicism. This fostered a consumer revolution in religious art and architecture as architects, religious figures and a Catholic bourgeoisie aspired to recreate the architectural magnificence and status associated with Catholic churches of the medieval period in Ireland and Europe. The characteristic splendour of these interiors owes much to commercial producers of religious art from Britain and Europe. Makers of stained glass and decorative mosaics, in particular, dominated the Irish market even after the establishment of an Irish Arts and Crafts movement from the early 1890s and continued to thrive well into the twentieth century, even as Irish artist-designed church art grew more popular with patrons. This essay takes a fresh approach to analysing the spaces of Irish Catholicism by exploring the ‘backstage’ of religion from the perspective of commercial church art business history. It draws out two themes central to this Roundtable: the ways in which local sacred spaces and landscapes were impacted by transnational exchanges and processes, and the relationship between physical space and imaginative space in architectural production.
Laboratory Diagnosis of Primary Amoebic Meningoencephalitis
Authors: Rojo Juan U , Rajendran Rajkumar , Salazar Jose H
Published: January 2023

Primary amebic meningoencephalitis (PAM) is a fulminant fatal human disease caused by the free-living amoeba Naegleria fowleri. Infection occurs after inhalation of water containing the amoeba, typically after swimming in bodies of warm freshwater. N. fowleri migrates to the brain where it incites meningoencephalitis and cerebral edema leading to death of the patient 7 to 10 days postinfection. Although the disease is rare, it is almost always fatal and believed to be underreported. The incidence of PAM in countries other than the United States is unclear and possibly on track to being an emerging disease. Poor prognosis is caused by rapid progression, suboptimal treatment, and underdiagnosis. As diagnosis is often performed postmortem and testing is only performed by a few laboratories, more accessible testing is necessary. This article reviews the current methods used in the screening and confirmation of PAM and makes recommendations for improved diagnostic practices and awareness.
Eco-friendly synthesis of silver nanoparticles using Eisenia bicyclis seaweed, their antimicrobial and anticancer activities
Authors: Badr Hoida Ali , Sayed Sherif A , Obiedallah Marwa
Published: January 2023

Silver nanoparticle (AgNPs) production with antibacterial and antitumor properties is an important application in the medical field. This study introduces a novel organism that can be used for the large-scale production of AgNPs. The edible brown alga Eisenia bicyclis was used as a reducing agent to biosynthesize stable AgNPs.

In this study, we achieved producing 50 mg AgNPs using only 1 g dried E. bicyclis seaweed. AgNP biosynthesis was performed at optimized conditions of a reaction temperature of 90°C, a seaweed extract concentration of 0.4%, and an AgNO3 concentration of 0.5 mM within 20 min, and the results showed that the formed nanoparticles are spherical and monodispersed with an average size 18.5 ± 1.2 nm. The antibacterial activity of biosynthesized AgNPs was evaluated against some human clinical pathogens. Results showed that AgNPs had antibacterial activity against all tested bacterial strains, with the appearance of a clear zone equal to or larger than positive controls. Also, there was a concentration-dependent growth inhibition of in vitro cultured breast cancer cells treated with AgNPs and overexpression of p53 and Bax, and underexpression of Bcl-2. AgNPs synthesized by this method provide a potential source for antibacterial and anticancer applications.
Impact of filter material and holding time on spore sampling efficiency in water
Authors: Ratliff Katherine , Abdel-Hady Ahmed , Monge Mariela , Mikelonis Anne , Touati Abderrahmane
Published: January 2023

Bacillus anthracis and other environmentally persistent pathogens pose a significant threat to human and environmental health. If contamination is spread over a wide area (e.g. resulting from a bioterrorism or biowarfare incident), readily deployable and scalable sample collection methods will be necessary for rapidly developing and implementing effective remediation strategies. A recent surge in environmental (eDNA) sampling technologies could prove useful for quantifying the extent and levels of contamination from biological agents in environmental and drinking water. In this study, three commonly used membrane filtration materials (cellulose acetate, cellulose nitrate, and nylon) were evaluated for spore filtration efficiency, yielding recoveries from 17%–68% to 25%–117% for high and low titer samples, respectively, where cellulose nitrate filters generated the highest recoveries. A holding time test revealed no statistically significant differences between spore recoveries when analyzed at the specified timepoints, suggesting that eDNA filter sampling techniques can yield and maintain a relatively high recovery of spores for an extended period of time between filtration and analysis without a detrimental impact on spore recoveries. The results shown here indicate that emerging eDNA technologies could be leveraged for sampling following a wide-area contamination incident and for other microbiological water sampling applications.
The Photonic Atom Probe as a Tool for the Analysis of the Effect of Defects on the Luminescence of Nitride Quantum Structures
Authors: Dimkou Ioanna , Houard Jonathan , Rochat Névine , Dalapati Pradip , Di Russo Enrico , Cooper David , Grenier Adeline , Monroy Eva , Rigutti Lorenzo
Published: January 2023

By collecting simultaneously optical and chemical/morphological data from nanoscale volumes, the Photonic Atom Probe (PAP) can be applied not only to the study of the relationship between optical and structural properties of quantum emitter but also to evaluate the influence of other factors, such as the presence of point defects, on the photoluminescence. Through the analysis of multiple layers of InGaN/GaN quantum dots (QDs), grown so that the density of structural defects is higher with increasing distance from the substrate, we establish that the light emission is higher in the regions exhibiting a higher presence of structural defects. While the presence of intrinsic point defects with non-radiative recombination properties remains elusive, our result is consistent with the fact that QD layers closer to the substrate behave as traps for non-radiative point defects. This result demonstrates the potential of the PAP as a technique for the study of the optical properties of defects in semiconductors.
Fountain-driven gas accretion feeding star formation over the disc of NGC 2403
Authors: Li Anqi , Fraternali Filippo , Marasco Antonino , Trager Scott C , Pezzulli Gabriele , Mancera Piña Pavel E , Verheijen Marc A W
Published: January 2023

We use a dynamical model of galactic fountain to study the neutral extraplanar gas (EPG) in the nearby spiral galaxy NGC 2403. We have modelled the EPG as a combination of material ejected from the disc by stellar feedback (i.e. galactic fountain) and gas accreting from the inner circumgalactic medium (CGM). This accretion is expected to occur because of cooling/condensation of the hot CGM (corona) triggered by the fountain. Our dynamical model reproduces the distribution and kinematics of the EPG H i emission in NGC 2403 remarkably well and suggests a total EPG mass of $4.7^{+1.2}_{-0.9}\times 10^8\, \mathrm{M_\odot }$, with a typical scale height of around 1 kpc and a vertical gradient of the rotation velocity of $-10.0\pm 2.7\, \mathrm{km\, s^{-1}\, kpc^{-1}}$. The best-fitting model requires a characteristic outflow velocity of $50\pm 10\, \mathrm{km\, s^{-1}}$. The outflowing gas starts out mostly ionized and only becomes neutral later in the trajectory. The accretion rate from the condensation of the inner hot CGM inferred by the model is 0.8 $\mathrm{M}_\odot \, \mathrm{yr}^{-1}$, approximately equal to the star-formation rate in this galaxy (0.6 $\mathrm{M}_\odot \, \mathrm{yr}^{-1}$). We show that the accretion profile, which peaks at a radius of about 4.5 kpc, predicts a disc growth rate compatible with the observed value. Our results indicate that fountain-driven corona condensation is a likely mechanism to sustain star formation, as well as the disc inside-out growth in local disc galaxies.
The nature and origins of the low surface brightness outskirts of massive, central galaxies in Subaru HSC
Authors: Jackson Thomas M , Pasquali Anna , La Barbera Francesco , More Surhud , Grebel Eva K
Published: January 2023

We explore the stellar mass density and colour profiles of 118 low redshift, massive, central galaxies, selected to have assembled 90 per cent of their stellar mass 6 Gyr ago, finding evidence of the minor merger activity expected to be the driver behind the size growth of quiescent galaxies. We use imaging data in the g, r, i, z, y bands from the Subaru Hyper Suprime-Cam survey and perform SED fitting to construct spatially well-resolved radial profiles in colour and stellar mass surface density. Our visual morphological classification reveals that ∼42 per cent of our sample displays tidal features, similar to previous studies, ∼43 per cent of the remaining sample displays a diffuse stellar halo, and only ∼14 per cent displays no features, down to a limiting μr-band ∼ 28 mag arcsec−2. We find good agreement between the stacked colour profiles of our sample to those derived from previous studies and an expected smooth, declining stellar mass surface density profile in the central regions (< 3 Re). However, we also see a flattening of the profile (Σ* ∼ 107.5 M⊙ kpc−2) in the outskirts (up to 10 Re), which is revealed by our method of specifically targeting tidal/accretion features. We find similar levels of tidal features and behaviour in the stellar mass surface density profiles in a younger comparison sample, however, a lack of diffuse haloes. We also apply stacking techniques similar to those in previous studies, finding such procedures wash out tidal features and thereby produce smooth declining profiles. The stellar material in the outskirts contributes on average ∼1010 M⊙ or a few per cent of the total stellar mass and has similar colours to SDSS satellites of similar stellar mass.
Using angular two-point correlations to self-calibrate the photometric redshift distributions of DECaLS DR9
Authors: Xu Haojie , Zhang Pengjie , Peng Hui , Yu Yu , Zhang Le , Yao Ji , Qin Jian , Sun Zeyang , He Min , Yang Xiaohu
Published: January 2023

Calibrating the redshift distributions of photometric galaxy samples is essential in weak lensing studies. The self-calibration method combines angular auto- and cross-correlations between galaxies in multiple photometric redshift (photo-z) bins to reconstruct the scattering rates matrix between redshift bins. In this paper, we test a recently proposed self-calibration algorithm using the DECaLS Data Release 9 and investigate to what extent the scattering rates are determined. We first mitigate the spurious angular correlations due to imaging systematics by a machine learning based method. We then improve the algorithm for χ2 minimization and error estimation. Finally, we solve for the scattering matrices, carry out a series of consistency tests, and find reasonable agreements: (1) finer photo-z bins return a high-resolution scattering matrix, and it is broadly consistent with the low-resolution matrix from wider bins; (2) the scattering matrix from the Northern Galactic Cap is almost identical to that from Southern Galactic Cap; (3) the scattering matrices are in reasonable agreement with those constructed from the power spectrum and the weighted spectroscopic subsample. We also evaluate the impact of cosmic magnification. Although it changes little the diagonal elements of the scattering matrix, it affects the off-diagonals significantly. The scattering matrix also shows some dependence on scale cut of input correlations, which may be related to a known numerical degeneracy between certain scattering pairs. This work demonstrates the feasibility of the self-calibration method in real data and provides a practical alternative to calibrate the redshift distributions of photometric samples.
Size-selective accretion of dust on to CPDs: low CPD masses and filtration of larger grains
Authors: Karlin Samuel M , Panić Olja , van Loo Sven
Published: January 2023

The major satellites of Jupiter and Saturn are believed to have formed in circumplanetary discs (CPDs), which orbit forming giant protoplanets. Gas and dust in CPDs have different distributions and affect each other by drag, which varies with grain size. Yet simulations of multiple dust grain sizes with separate dynamics have not been done before. We seek to assess how much dust of each grain size there is in CPDs. We run multifluid 3D hydrodynamical simulations including gas and four discrete grain sizes of dust from 1 μm to 1 mm, representing a continuous distribution. We consider a 1MJup protoplanet embedded in a protoplanetary disc around a 1 M⊙ star. Our results show a truncated MRN (Mathis-Rumpl-Nordsieck) distribution at smaller grain sizes, which starts to tail off by a = 100 μm and is near zero at 1 mm. Large dust grains, which hold most of the dust mass, have very inefficient accretion to the CPD, due to dust filtration. Therefore, CPDs’ dust masses must be small, with mass ratio ∼ a few × 10−6 to the protoplanet. These masses and the corresponding millimetre opacities are in line with CPD fluxes observed to date.
Multifrequency variability study of flat-spectrum radio quasar PKS 0346-27
Authors: Kamaram Sushanth Reddy , Prince Raj , Pramanick Suman , Bose Debanjan
Published: January 2023

We have presented a multiwavelength temporal and spectral study of the blazar PKS 0346-27 for the period 2019 January–2021 December (MJD 58484–59575) using data from Fermi-LAT (γ-rays), Swift-XRT (X-rays), and Swift-UVOT (ultraviolet and optical). We identified multiple flaring episodes by analysing the gamma-ray light curve generated from the Fermi-LAT data over a 2-yr period. The light curves of these individual gamma-ray flares with 1-d binning were then modelled using a sum-of-exponentials fit. We found the minimum variability times for the gamma-ray light curve to be 1.34 ± 0.3 d and a range of 0.1–3.2 d for the Swift wavelengths, suggesting the compactness of the source. The broad-band emission mechanism was studied by modelling the simultaneous multiwaveband spectral energy distributions (SEDs) using the one-zone leptonic emission mechanism. We found that the optical-UV and X-ray data can be explained by the synchrotron and synchrotron self-Compton (SSC) emissions. However, the disc component of the external Compton (EC) radiation is dominant at higher energies with contributions from the EC broad-line region component and SSC. Further, we performed a power spectral density analysis with data from the gamma-ray light curve using the power spectrum response method. With the power-law model, the best-fitting slope of 2.15 ± 0.87 was found. This source could be a promising target for the upcoming Cherenkov telescope array for its harder spectrum at lower energies (tens of GeV).
HiJAKing Immunotherapy-Resistant Melanoma for a Cure
Authors: Shi Lewis Zhichang , Shen Hongxing , Ojo Oluwagbemiga A , Bonner James A
Published: January 2023

Immune checkpoint blockers (ICBs) have brought great promise to patients with advanced melanoma, a tumor type that was claimed largely incurable not long ago. However, therapeutic resistance to ICBs has limited their utility in the clinic. Here, we provide a commentary on recent research endeavors concerning ICB resistance in melanoma patients.
An international survey of current management practices for polymyalgia rheumatica by general practitioners and rheumatologists
Authors: Donskov Agnete Overgaard , Mackie Sarah Louise , Hauge Ellen Margrethe , Toro-Gutiérrez Carlos Enrique , Hansen Ib Tønder , Hemmig Andrea Katharina , Van der Maas Aatke , Gheita Tamer , Nielsen Berit Dalsgaard , Douglas Karen M J , Conway Richard , Rezus Elena , Dasgupta Bhaskar , Monti Sara , Matteson Eric L , Sattui Sebastian E , Matza Mark , Ocampo Vanessa , Gromova Margarita , Grainger Rebecca , Bran Andrea , Appenzeller Simone , Goecke Annelise , Colman Nelly , Keen Helen I , Kuwana Masataka , Gupta Latika , Salim Babur , Harifi Ghita , Erraoui Mariam , Ziade Nelly , Al-Ani Nizar Abdulateef , Ajibade Adeola , Knitza Johannes , Frølund Line , Yates Max , Pimentel-Quiroz Victor R , Lyrio Andre Marun , Sandovici Maria , Van der Geest Kornelis S M , Helliwell Toby , Brouwer Elisabeth , Dejaco Christian , Keller Kresten Krarup
Published: January 2023

Objectives

To explore current management practices for PMR by general practitioners (GPs) and rheumatologists including implications for clinical trial recruitment.

Methods

An English language questionnaire was constructed by a working group of rheumatologists and GPs from six countries. The questionnaire focused on: 1: Respondent characteristics; 2: Referral practices; 3: Treatment with glucocorticoids; 4: Diagnostics; 5: Comorbidities; and 6: Barriers to research. The questionnaire was distributed to rheumatologists and GPs worldwide via members of the International PMR/Giant Cell Arteritis Study Group.

Results

In total, 394 GPs and 937 rheumatologists responded to the survey. GPs referred a median of 25% of their suspected PMR patients for diagnosis and 50% of these were returned to their GP for management. In general, 39% of rheumatologists evaluated patients with suspected PMR >2 weeks after referral, and a median of 50% of patients had started prednisolone before rheumatologist evaluation. Direct comparison of initial treatment showed that the percentage prescribing >25 mg prednisolone daily for patients was 30% for GPs and 12% for rheumatologists. Diagnostic imaging was rarely used. More than half (56%) of rheumatologists experienced difficulties recruiting people with PMR to clinical trials.

Conclusion

This large international survey indicates that a large proportion of people with PMR are not referred for diagnosis, and that the proportion of treatment-naive patients declined with increasing time from referral to assessment. Strategies are needed to change referral and management of people with PMR, to improve clinical practice and facilitate recruitment to clinical trials.
Role of MEF2C in the Endothelial Cells Derived from Human Induced Pluripotent Stem Cells
Authors: Li Tao , Conroy Kelsey L , Kim Amy M , Halmai Julian , Gao Kewa , Moreno Emily , Wang Aijun , Passerini Anthony G , Nolta Jan A , Zhou Ping
Published: January 2023

Human induced pluripotent stem cells (hiPSCs) not only provide an abundant source of vascular cells for potential therapeutic applications in vascular disease but also constitute an excellent model for understanding the mechanisms that regulate the differentiation and the functionality of vascular cells. Here, we reported that myocyte enhancer factor 2C (MEF2C) transcription factor, but not any other members of the MEF2 family, was robustly upregulated during the differentiation of vascular progenitors and endothelial cells (ECs) from hiPSCs. Vascular endothelial growth factors (VEGF) strongly induced MEF2C expression in endothelial lineage cells. The specific upregulation of MEF2C during the commitment of endothelial lineage was dependent on the extracellular signal regulated kinase (ERK). Moreover, knockdown of MEF2C with shRNA in hiPSCs did not affect the differentiation of ECs from these hiPSCs, but greatly reduced the migration and tube formation capacity of the hiPSC-derived ECs. Through a chromatin immunoprecipitation-sequencing, genome-wide RNA-sequencing, quantitative RT-PCR, and immunostaining analyses of the hiPSC-derived endothelial lineage cells with MEF2C inhibition or knockdown compared to control hiPSC-derived ECs, we identified TNF-related apoptosis inducing ligand (TRAIL) and transmembrane protein 100 (TMEM100) as novel targets of MEF2C. This study demonstrates an important role for MEF2C in regulating human EC functions and highlights MEF2C and its downstream effectors as potential targets to treat vascular malfunction-associated diseases.
Effect of recent floods on women’s reproductive health in Pakistan: an alarming situation
Authors: Ochani Sidhant , Aaqil Syeda Ilsa , Nazir Abubakar , Athar Fatima Binte , Ullah Kaleem
Published: January 2023

The most frequent natural calamity in developed and developing nations is flooding, which has significantly increased morbidity and mortality globally. Over the previous 30 years, flooding has harmed more than 2.8 billion people globally and claimed the lives of over 200,000 individuals. The effect of floods on a population’s health varies depending on the population’s vulnerability. It greatly impairs the quality of life of everyone in the affected area. However, pregnant women are more vulnerable to the negative impact of flood-related changes, and floods may have a variety of detrimental psychological and pathological impacts on women’s reproductive health. The UN Population Fund predicts that 1700 women will give birth each day, and ~500,000 pregnant women will be affected by the catastrophe of the flood. According to the United Nations Population Fund (UNFPA), about 650,000 pregnant women in flood-affected areas need maternal health services to ensure a healthy pregnancy and delivery. Up to 73,000 expectant mothers will require competent delivery attendants, neonatal care, and support in the upcoming month.
Novel metabolic phenotypes for extrahepatic complication of nonalcoholic fatty liver disease
Authors: Yi Jiayi , Wang Lili , Guo Jiajun , Ren Xiangpeng
Published: January 2023

Background and Aims:

Phenotypic heterogeneity among patients with NAFLD is poorly understood. We aim to identify clinically important phenotypes within NAFLD patients and assess the long-term outcomes among different phenotypes.

Methods:

We analyzed the clinical data of 2311 participants from the Third National Health and Nutrition Examination Survey (NHANES III) and their linked mortality data through December 2019. NAFLD was diagnosed by ultrasonographic evidence of hepatic steatosis without other liver diseases and excess alcohol use. A 2-stage cluster analysis was applied to identify clinical phenotypes. We used Cox proportional hazard models to explore all-cause and cause-specific mortality between clusters.

Results:

We identified 3 NAFLD phenotypes. Cluster 1 was characterized by young female patients with better metabolic profiles and lower prevalence of comorbidities; Cluster 2 by obese females with significant insulin resistance, diabetes, inflammation, and advanced fibrosis and Cluster 3 by male patients with hypertension, atherogenic dyslipidemia, and liver and kidney damage. In a median follow-up of 26 years, 989 (42.8%) all-cause mortality occurred. Cluster 1 patients presented the best prognosis, whereas Cluster 2 and 3 had higher risks of all-cause (Cluster 2—adjusted HR: 1.48, 95% CI: 1.16–1.90; Cluster 3—adjusted HR: 1.29, 95% CI: 1.01–1.64) and cardiovascular (Cluster 2—adjusted HR: 2.01, 95% CI: 1.18–3.44; Cluster 3—adjusted HR: 1.75, 95% CI: 1.03–2.97) mortality.

Conclusions:

Three phenotypically distinct and clinically meaningful NAFLD subgroups have been identified with different characteristics of metabolic profiles. This study reveals the substantial disease heterogeneity that exists among NAFLD patients and underscores the need for granular assessments to define phenotypes and improve clinical practice.
Postnatal CMV Infection and Antiviral Treatment in Extremely Premature Infants: A 12-Year Retrospective Analysis
Authors: Košiček Rok , Kristan Borut , Erčulj Vanja , Kornhauser Cerar Lilijana , Petrovec Miroslav , Pokorn Marko , Spirovska Ana , Uršič Tina , Grosek Štefan
Published: January 2023

Background:

The impact and outcomes of postnatal cytomegalovirus (CMV) infection are not entirely clear. We aimed to determine the associations between treatment outcomes of postnatal CMV infection and its antiviral treatment.

Methods:

Retrospective study in a tertiary center. Infants of < 29 weeks gestational age who were tested for postnatal CMV infection were included. CMV-infected infants were compared to uninfected infants (control group). CMV-infected infants were either treated with ganciclovir and/or valganciclovir (CMVPT group) or not (CMVPNT group). Demographic, clinical, laboratory, treatment, and outcome data were collected. Primary outcomes were the length of stay, death before discharge and hearing impairment, cognitive and motor development as assessed by the Denver Developmental Screening Test II, and neurologic impairment at the corrected age of 1.5–2 years.

Results:

We included 103 extremely premature infants. The Median (interquartile range [IQR]) length of stay was 94 (69–112) days in control, 85 (70–102) days in CMVPNT, and 100 (88–137) days in the CMVPT group. Mortality before discharge was 6% in control, 3.8% in CMVPNT, and 3.7% in the CMVPT group. Normal hearing at follow-up was found in 30/37 infants in control (81.1%), 13/13 infants in CMVPNT (100%), and 17/20 infants in the CMVPT group (85%). Denver Developmental Screening Test II results did not differ among the three groups. Neurologic impairment was found in 21/37 infants (56.8%) in control, 9/13 infants in CMVPNT (69.2%), and 14/20 infants in CMVPT group (70%).

Conclusions:

The associations between antiviral treatment of postnatal CMV infection and better treatment outcomes were nonsignificant.
Higher Troponin Levels on Admission are associated With Persistent Cardiac Magnetic Resonance Lesions in Children Developing Myocarditis After mRNA-Based COVID-19 Vaccination
Authors: Manno Emma Concetta , Amodio Donato , Cotugno Nicola , Rossetti Chiara , Giancotta Carmela , Santilli Veronica , Zangari Paola , Rotulo Gioacchino Andrea , Villani Alberto , Giglioni Emanuele , Turchetta Attilio , Cafiero Giulia , Franceschini Alessio , Chinali Marcello , Porzio Ottavia , Secinaro Aurelio , Palma Paolo
Published: January 2023

Background:

Acute pericarditis/myocarditis is a rare complication of the mRNA-based vaccines and although mostly self-limiting, long-term sequelae remain unclear.

Methods:

We enrolled all patients admitted to the emergency department between September 2021 and February 2022 meeting the CDC work case definition, with symptoms onset after mRNA-based COVID-19 vaccine. Alternative virologic causes were excluded. Clinical data, laboratory values, cardiologic evaluation, electrocardiogram (ECG), and echocardiogram (ECHO) were collected on admission, at discharge, and during follow-up in all patients. Cardiac Magnetic Resonance (CMR) was performed only in those with signs consistent with myocarditis.

Results:

We observed 13 patients (11M and 2F), median age 15 years, affected by acute pericarditis/myocarditis after COVID-19 mRNA vaccination (11 after Comirnaty® and 2 after Spikevax®). Symptoms’onset occurred at a median of 5 days (range, 1 to 41 days) after receiving mRNA vaccine (13 Prizer 2 Moderna): 4 patients (31%) after the 1st dose, 6 (46%) after the 2nd, and 3 (23%) after 3rd dose. Increased levels of high-sensitive troponin T (hsTnT) (median 519,5 ng/mL) and N-terminal-pro hormone BNP (NT-proBNP) (median 268 pg/mL) and pathognomonic ECG and ECHO abnormalities were detected. On admission, 7 of 13 (54%) presented with myopericarditis, 3 (23%) with myocarditis, and 3 (23%) with pericarditis; CMR was performed in 5 patients upon pediatric cardiologist prescription and findings were consistent with myocarditis. At 12 weeks of follow-up, all but one patient (92%), still presenting mild pericardial effusion at ECHO, were asymptomatic with normal hsTnT and NT-proBNP levels and ECG. On CMR 6 of 9 patients showed persistent, although decreased, myocardial injury. Higher hsTnT levels on admission significantly correlated with persistent CMR lesions.

Conclusion:

Evidence of persistent CMR lesions highlights the need for a close and standardized follow-up for those patients who present high hsTnT levels on admission.
Fluctuations in Pediatric Acute Otitis Media Burden During the First Two COVID-19 Years in Israel
Authors: Zloczower Elchanan , Pitaro Jacob , Hazan Itai , Warman Meir , Ziv Oren , Yaakov Omer , Marom Tal
Published: January 2023

Background:

To study pediatric acute otitis media (AOM) burden fluctuations before and during the first two COVID years, which were characterized by measures to reduce the spread of airborne diseases. We used urinary tract infection (UTI) as a comparison infection.

Methods:

This was a cross-sectional study encompassing three pre-COVID years (March 1, 2017–February 29, 2020) and the first two COVID years (March 1, 2020–February 28, 2021, and March 1, 2021-February 28, 2022). Records were retrieved from the Clalit Health Services database, Israel’s largest healthcare maintenance organization. Children 0–15 years with AOM and UTI episodes were categorized according to age (1>, 1–4, 5–15 years). We collected demographics, seasonality, AOM complications, antibiotic prescriptions, and recent COVID-19 infections. The average AOM/UTI rates of the three pre-COVID years vs. two COVID years were used to calculate the incidence rate ratios (IRRs).

Results:

We identified 1,102,826 AOM and 121,263 UTI episodes. The median age at AOM diagnosis was 2.0 years (IQR, 1.1–4.1). Male predominance, age at presentation, and the dominant age group of 1–4 years did not change during the COVID years. While UTI episode rates decreased during the COVID years (IRR 0.76, 95% CI, 0.68–0.84, P < 0.001), the reduction in AOM episode rates was >2-fold (IRR 0.46, 95% CI, 0.34–0.63, P < 0.001). The largest decrease was observed among children 1–4 years old during the first COVID year (β=−1,938 AOM episodes/100,00 children, 95% CI, −2,038 to −1,912, P < 0.001). Recent COVID-19 infection was associated with low AOM morbidity (IRR 0.05, 95% CI 0.05–0.05, P < 0.001).

Conclusions:

AOM burden substantially decreased during the first COVID year but almost reached pre-pandemic levels during the second year.
Ageing and chronic obstructive pulmonary disease: interrelationships
Authors: Kakkera Krishna , Atchley William T. , Kodali Maneetha , Bartter Thaddeus
Published: January 2023

Purpose of review

As life expectancy increases, the ageing population accrues an increasing burden of chronic conditions and functional compromise. Some conditions that lead to compromise are deemed part of ‘natural ageing,’ whereas others are considered to represent disease processes. Ageing (’a natural process’) and chronic obstructive pulmonary disease (’a disease’) share many common features, both pulmonary and systemic. At times, the pathways of injury are the same, and at times they are concurrent. In some cases, age and disease are separated not by the presence but by the severity of a finding or condition. This brief review aims to compare some of the similarities between ageing and COPD and to compare/contrast mechanisms for each.

Recent findings

At the cellular level, the natural process of ageing includes multiple systemic and molecular mechanisms. COPD, though defined by progressive pulmonary compromise, can also be a systemic disease/process. It has become evident that specific senescence pathways like p-16 and the sirtuin family of proteins are implicated both in ageing and in COPD. Also common to both ageing and COPD are increased inflammatory markers, leucocyte response abnormalities, and DNA-level abnormalities.

The prevalence of COPD increases with increasing age. COPD contributes to the accrued burden of chronic disease and is a significant contributor to morbidity and mortality in this population. This review attempts to summarize some of similarities between ageing and COPD and their underlying mechanisms.
Effects of GLP-1 on ovarian dysfunction in polycystic ovary syndrome: A protocol for systematic review and meta-analysis
Authors: Zhang Caifeng , Yan Dongling , Wang Xiaojing , Cheng Dianchen
Published: January 2023

Background:

Polycystic ovary syndrome (PCOS) is a frequent endocrine disorder in women, it is the principal cause of infertility and amenorrhea. Due to its high recurrence rate, poor prognosis and serious complications, more works on the research of PCOS are needed. Therefore, we performed a protocol for systematic review and meta-analysis to investigate the efficacy and safety of glucagon-like peptide-1 receptor agonists on ovarian dysfunction in PCOS.

Methods:

This study protocol has been registered in the PROSPERO and the registration number is CRD42020188247. The procedure of this protocol will be conducted according to the Preferred Reporting Item for Systematic Review and Meta-analysis Protocols guidance. A comprehensive search of several databases from 1966 to November 2022 will be conducted. The databases includes Ovid Medline In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and PubMed. The risk of bias of the included studies will be assessed using the Cochrane tool of risk of bias. All statistical analyses will be conducted using the software program Review Manager version 5.3.

Results:

The results of this systematic review will be published in a peer-reviewed journal.

Conclusion:

This systematic review will provide evidence to judge whether glucagon-like peptide-1 receptor agonist is superior to metformin in patients with PCOS.
QRS-T angle as a predictor of pulmonary arterial hypertension: A review
Authors: Li Bo , Liu Xuhan , Wang Baoguo , Liu Xiuqing , Zhang Weihua
Published: January 2023

Spatial QRS-T angle is a vector projection of ventricular gradient, reflecting the heterogeneity of ventricular repolarization. The QRS vector is projected into three dimensional (3D) space to obtain the frontal QRSf vector and Tf vector. The frontal QRS-T Angle can be obtained by simple calculation. In several studies of diseases that cause pulmonary hypertension, there has been evidence that changes in the QRS-T Angle can predict disease. Electrocardiogram (ECG) is a cheap and noninvasive test, and its clinical significance in the diagnosis of pulmonary hypertension should be further studied.