bluuebunny/crossref_metadata_2025 huggingface dataset:
Mucosal Addressin Cell Adhesion Molecule 1 Expression Reflects Mucosal Inflammation and Subsequent Relapse in Patients with Ulcerative Colitis
Authors: Uchiyama Kazuhiko , Takagi Tomohisa , Mizushima Katsura , Hirai Yasuko , Asaeda Kohei , Sugaya Takeshi , Kajiwara-Kubota Mariko , Kashiwagi Saori , Minagawa, Yuki , Hotta Yuma , Tanaka Makoto , Inoue Ken , Katada Kazuhiro , Kamada Kazuhiro , Ishikawa Takeshi , Yasuda Hiroaki , Konishi Hideyuki , Kishimoto Mitsuo , Naito Yuji , Itoh Yoshito
Published: December 2022

Background and Aims

Mucosal addressin cell adhesion molecule 1 [MAdCAM-1] is upregulated in the vascular endothelium of the colonic mucosa in ulcerative colitis [UC]. Although the association between MAdCAM-1 expression and mucosal inflammation has been discussed, the association with the clinical course of UC patients has not been reported. In this study we investigated not only the association between mucosal MAdCAM-1 expression and mucosal inflammation, but also its association with subsequent relapse in UC patients with clinical remission.

Methods

Eighty UC patients in remission who visited Kyoto Prefectural University of Medicine for follow-up for 2 years were included. Biopsy samples were collected during colonoscopy, and transcriptional expression levels of UC-related cytokines and MAdCAM-1 were quantified using real-time polymerase chain reaction. MAdCAM-1 mRNA expression and protein expression by immunohistochemistry were compared in patients who subsequently relapsed and those who remained in remission and were examined in relation to endoscopic findings, histological activity and cytokine expression.

Results

MAdCAM-1 expression was correlated with endoscopic severity, and significantly elevated in histologically active mucosa than inactive mucosa. Furthermore, MAdCAM-1 expression levels were closely correlated with those of several cytokines. MAdCAM-1 mRNA and protein expression were significantly higher in the relapse group than in the remission group, indicating that MAdCAM-1 expression in the mucosa is already elevated in UC patients in clinical remission who subsequently relapse.

Conclusions

MAdCAM-1 expression in the colonic mucosa of UC patients is related to mucosal inflammation and subsequent relapse; it may serve as a marker for both relapse and therapeutic effectiveness in UC.
Influence of age at surgery on left ventricular strain in patients with anomalous origin of left coronary artery from pulmonary artery
Authors: Kakarla Saikiran , Sasikumar Deepa , Varma Ravi Prasad , Kurup Harikrishnan K N , Gopalakrishnan Arun , Nair Krishna Kumar Mohanan , Dharan Baiju S , Krishnamoorthy Kavasseri M
Published: December 2022

OBJECTIVES

Myocardial strain abnormalities are described after surgical repair of anomalous left coronary artery from pulmonary artery (ALCAPA) even after recovery of ventricular function. The factors that predispose to the presence of these strain abnormalities in the presence of normal ventricular function are unknown. The aim of this study was to find out whether the age at repair influences the presence of global and regional strain abnormalities on follow-up.

METHODS

Repaired ALCAPA patients from a single centre (n = 40) with good ventricular ejection fraction on follow-up were recruited. Baseline and follow-up data were collected from electronic records. Global and regional myocardial strain assessment was done by speckle tracking echocardiography prospectively. The association between age at repair and strain abnormalities on follow-up was analysed.

RESULTS

The patients who presented earlier had significantly worse ventricular function pre-operatively compared to older patients (P < 0.0005). Global longitudinal strain was abnormal in 40% of patients with normal ventricular ejection fraction on follow-up. Presence of longitudinal strain abnormalities was more in patients who underwent repair at older age than in those who were repaired earlier (P < 0.0005). The probability of having normal longitudinal strain on follow-up was 81.6% if surgery was done before 7.8 months of age. If operated before 6 months, the odds of having normal myocardial strain was 11 times higher. Regional strain abnormalities of varying severity were present in all patients in the left and in some patients in the right coronary artery territories.

CONCLUSIONS

Older age at ALCAPA repair is associated with increased incidence of myocardial strain abnormalities. Regional strain abnormalities were found in both left and right coronary artery territories.
Associations of multidimensional fatigue with the physical, psychological, and situational factors in outpatients with heart failure: a cross-sectional study
Authors: Higa Hiroko , Lennie Terry A , Chung Misook L , Tsuchihashi-Makaya Miyuki
Published: December 2022

Aims

Fatigue, a distressing symptom in patients with heart failure (HF), is associated with progress and health outcomes. Fatigue has been identified as having multidimensions, but a few studies have used a multidimensional fatigue scale. Many factors related to HF, including physical, psychological, and situational factors, may impact fatigue. However, there is limited knowledge about how these HF-related factors are associated with multidimensional fatigue in outpatients with HF in Japan. The aim of this study was to identify HF-related factors [physical; clinical characteristics, New York Heart Association (NYHA) functional class and physical function, psychological; depressive symptoms and anxiety, situational; health literacy and perceived control] associated with the five dimensions of fatigue in outpatients with HF.

Methods and results

Outpatients with HF (N = 165, mean age = 69.5 years, 78.8% male) completed the survey and physical assessment of gait speed. Fatigue was assessed using five dimensions of the Multidimensional Fatigue Inventory-20. Multiple linear regression analysis was conducted for each dimension of fatigue. General fatigue was predicted by age, NYHA, and perceived control. Physical fatigue was predicted by NYHA, depressive symptoms, and perceived control. Reduced activity was predicted by NYHA, gait speed, depressive symptoms, communicative health literacy, and critical health literacy. The reduced motivation was predicted by depressive symptoms and perceived control. Mental fatigue was predicted by depressive symptoms.

Conclusion

Different factors were significantly associated with each fatigue dimension. Further research is needed to alleviate fatigue in patients with HF.
Metagenomics and metatranscriptomics reveal broadly distributed, active, novel methanotrophs in the Gulf of Mexico hypoxic zone and in the marine water column
Authors: Howe Kathryn L , Seitz Kiley W , Campbell Lauren G , Baker Brett J , Thrash J Cameron , Rabalais Nancy N , Rogener Mary-Kate , Joye Samantha B , Mason Olivia U
Published: December 2022

The northern Gulf of Mexico (nGOM) hypoxic zone is a shallow water environment where methane, a potent greenhouse gas, fluxes from sediments to bottom water and remains trapped due to summertime stratification. When the water column is destratified, an active planktonic methanotrophic community could mitigate the efflux of methane, which accumulates to high concentrations, to the atmosphere. To investigate the possibility of such a biofilter in the nGOM hypoxic zone we performed metagenome assembly, and metagenomic and metatranscriptomic read mapping. Methane monooxygenase (pmoA) was an abundant transcript, yet few canonical methanotrophs have been reported in this environment, suggesting a role for non-canonical methanotrophs. To determine the identity of these methanotrophs, we reconstructed six novel metagenome-assembled genomes (MAGs) in the Planctomycetota, Verrucomicrobiota and one putative Latescibacterota, each with at least one pmoA gene copy. Based on ribosomal protein phylogeny, closely related microbes (mostly from Tara Oceans) and isolate genomes were selected and co-analyzed with the nGOM MAGs. Gene annotation and read mapping suggested that there is a large, diverse and unrecognized community of active aerobic methanotrophs in the nGOM hypoxic zone and in the global ocean that could mitigate methane flux to the atmosphere.
Genome assembly of Thaumatotibia leucotreta, a major polyphagous pest of agriculture in sub-Saharan Africa
Authors: Bierman Anandi , Karsten Minette , Terblanche John S
Published: December 2022

The false codling moth (FCM; Thaumatotibia leucotreta, Meyrick; Lepidoptera: Tortricidae) is a highly polyphagous, major agricultural pest indigenous to sub-Saharan Africa. With growing international trade, there is an increasing concern about introducing this pest into other countries. In South Africa, FCM poses a risk to multiple crops, and is currently suppressed through a combination of chemical, microbial, cultural, augmentative biological control, and the sterile insect technique. Compared with other lepidopteran agricultural pests, such as codling moth Cydia pomonella, genetic and other -omic resources for FCM have not been as well developed and/or not made publicly available to date. The need to develop genomic resources to address questions around insecticide resistance, chemosensory capabilities, and ultimately, develop novel control methods (e.g. gene editing) of this pest is highlighted. In this study, an adult male was sequenced using long-read PacBio Sequel II reads and Illumina NextSeq short reads and assembled using a hybrid assembly pipeline and Pilon error correction. Using the chromosome-level genome assembly of Cy. pomonella, we performed comparative analysis, arranged FCM scaffolds to chromosomes, and investigated genetic variation related to insecticide resistance and chemosensory capabilities. This work provides a platform upon which to build future genomic research on this economically important agricultural pest.
Third Places for Older Adults’ Social Engagement: A Scoping Review and Research Agenda
Authors: Sugiyama Masaaki , Chau Hing-Wah , Abe Takumi , Kato Yusuke , Jamei Elmira , Veeroja Piret , Mori Kazuhiko , Sugiyama Takemi
Published: December 2022

Background and Objectives

Neighborhood places that facilitate older residents to meet and interact (third places) receive an increasing research interest as studies have consistently shown the benefits of social engagement for older adults’ health. This scoping review synthesized the findings of studies examining the role of third places in older adults’ social engagement.

Research Design and Methods

Searching 5 databases (CINAHL, Medline, PsycInfo, Scopus, and Web of Science) in October 2021, this study identified quantitative and qualitative studies that examined the relationships between third places and social engagement (interaction and network) among older adults.

Results

A total of 32 studies (12 quantitative and 20 qualitative studies) met the eligibility criteria. These studies examined 4 types of third place, namely, community facilities, local businesses, open/green spaces, and transition spaces. More than two thirds of the studies reviewed found that access to community facilities, local businesses, and open/green spaces were related to older adults’ social interaction. For the relationships between third places and social networks, the importance of accessible local businesses and the quality of open/green spaces was supported by fewer studies.

Discussion and Implications

The findings of quantitative and qualitative studies suggest that local places that are convenient to visit and comfortable to stay in for older adults are likely to enhance their social interaction and network. However, more specific evidence is needed to inform the planning and design of third places. The review discusses future research topics that address the gaps identified in the current literature.
Localized adaptive waveform inversion: theory and numerical verification
Authors: Yong Peng , Brossier Romain , Métivier Ludovic , Virieux Jean
Published: December 2022

Correctly interpreting phase events thanks to data processing techniques based on correlation or deconvolution has been the focus of numerous studies in the field of high-resolution seismic imaging using full-waveform inversion. To mitigate the non-convexity of the misfit function and the risk to converge towards non-informative local minima, correlation and deconvolution techniques make it possible to focus on phase information instead of amplitude information and to design more convex misfit function, alleviating the dependency of the full-waveform inversion process on the accuracy of initial models. Such techniques however rely on the assumption that phase events can be compared one by one, or that all the phase events are shifted in time in a similar way. This assumption is not satisfied in practice, which limits the effectiveness of these correlation/deconvolution-based methods. To overcome this issue, we propose to account for the non-stationary relation between observed and predicted data through a local in-time deconvolution technique, based on time–frequency analysis of the signal using a Gabor transform. This makes it possible to estimate instantaneous time-shift between locally coherent phase events. This strategy generalizes the conventional normalized deconvolution technique, which has been popularized under the name of adaptive waveform inversion. To support the introduction of our novel method, we compare it with four misfit functions based respectively on classical cross-correlation, penalized cross-correlation, penalized deconvolution, and adaptive waveform inversion. We analyse the behaviour of these methods on specific scenarios, and then propose a comparison on 2-D synthetic benchmarks. We show how our ‘localized’ adaptive waveform inversion applies in these realistic tests and overcomes some of the limitations of the aforementioned techniques.
Estimating the burden of disease attributable to high ambient temperature across climate zones: methodological framework with a case study
Authors: Liu Jingwen , Hansen Alana , Varghese Blesson M , Dear Keith , Tong Michael , Prescott Vanessa , Dolar Vergil , Gourley Michelle , Driscoll Timothy , Zhang Ying , Morgan Geoffrey , Capon Anthony , Bi Peng
Published: December 2022

Background

With high temperature becoming an increasing health risk due to a changing climate, it is important to quantify the scale of the problem. However, estimating the burden of disease (BoD) attributable to high temperature can be challenging due to differences in risk patterns across geographical regions and data accessibility issues.

Methods

We present a methodological framework that uses Köppen–Geiger climate zones to refine exposure levels and quantifies the difference between the burden observed due to high temperatures and what would have been observed if the population had been exposed to the theoretical minimum risk exposure distribution (TMRED). Our proposed method aligned with the Australian Burden of Disease Study and included two parts: (i) estimation of the population attributable fractions (PAF); and then (ii) estimation of the BoD attributable to high temperature. We use suicide and self-inflicted injuries in Australia as an example, with most frequent temperatures (MFTs) as the minimum risk exposure threshold (TMRED).

Results

Our proposed framework to estimate the attributable BoD accounts for the importance of geographical variations of risk estimates between climate zones, and can be modified and adapted to other diseases and contexts that may be affected by high temperatures.

Conclusions

As the heat-related BoD may continue to increase in the future, this method is useful in estimating burdens across climate zones. This work may have important implications for preventive health measures, by enhancing the reproducibility and transparency of BoD research.
Affinity of cefotiam for the alternative penicillin binding protein PBP3SAL used by Salmonella inside host eukaryotic cells
Authors: Cestero Juan J , Castanheira Sónia , González Henar , Zaragoza Óscar , García-del Portillo Francisco
Published: December 2022

Background

Following the invasion of eukaryotic cells, Salmonella enterica serovar Typhimurium replaces PBP2/PBP3, main targets of β-lactam antibiotics, with PBP2SAL/PBP3SAL, two homologue peptidoglycan synthases absent in Escherichia coli. PBP3SAL promotes pathogen cell division in acidic environments independently of PBP3 and shows low affinity for β-lactams that bind to PBP3 such as aztreonam, cefepime, cefotaxime, ceftazidime, ceftriaxone, cefuroxime and cefalotin.

Objectives

To find compounds with high affinity for PBP3SAL to control Salmonella intracellular infections.

Methods

An S. Typhimurium ΔPBP3 mutant that divides using PBP3SAL and its parental wild-type strain, were exposed to a library of 1520 approved drugs in acidified (pH 4.6) nutrient-rich LB medium. Changes in optical density associated with cell filamentation, a read-out of blockage in cell division, were monitored. Compounds causing filamentation in the ΔPBP3 mutant but not in wild-type strain—the latter strain expressing both PBP3 and PBP3SAL in LB pH 4.6—were selected for further study. The bactericidal effect due to PBP3SAL inhibition was evaluated in vitro using a bacterial infection model of cultured fibroblasts.

Results

The cephalosporin cefotiam exhibited higher affinity for PBP3SAL than for PBP3 in bacteria growing in acidified LB pH 4.6 medium. Cefotiam also proved to be effective against intracellular Salmonella in a PBP3SAL-dependent manner. Conversely, cefuroxime, which has higher affinity for PBP3, showed decreased effectiveness in killing intracellular Salmonella.

Conclusions

Antibiotics with affinity for PBP3SAL, like the cephalosporin cefotiam, have therapeutic value for treating Salmonella intracellular infections.
Wind turbine maximum power point tracking control based on unsupervised neural networks
Authors: Muñoz-Palomeque Eduardo , Sierra-García J Enrique , Santos Matilde
Published: December 2022

The main control goal of a wind turbine (WT) is to produce the maximum energy in any operating region. When the wind speed is under its rated value, the control must aim at tracking the maximum power point of the best power curve for a specific WT. This is challenging due to the non-linear characteristics of the system and the environmental disturbances it is subjected to. Direct speed control (DSC) is one of the main techniques applied to address this problem. In this strategy, it is necessary to design a speed controller to adjust the generator torque so to follow the optimum generator speed. In this work, we improve the DSC by implementing this speed controller with a radial basis function neural network (NN). An unsupervised learning algorithm is designed to tune the weights of the NN so it learns the control law that minimizes the generator speed error. With this proposed unsupervised neural control methodology, the electromagnetic torque that allows the optimal power extraction is obtained, and thus the best power coefficient (${C}_\mathrm{p}$) values. The proposal is tested on the OpenFAST non-linear model of the National Renewable Energy Laboratory 1.5 MW WT. Simulation results prove the good performance of this neuro-control approach as it maintains the WT variables into the appropriate range and tracks the rated operation values. It has been compared with the controller included in OpenFAST giving up to 7.87% more power.
Arteriovenous malformation of small intestine successfully treated by double-balloon enteroscopy and laparoscope-assisted surgery
Authors: Tohma Takayuki , Okabe Yasuyuki , Ushio Masaya , Saito Masaya
Published: December 2022

Arteriovenous malformation (AVM) of the small bowel is a rare disease and can be sometimes difficult to treat due to the diagnostic difficulty. We herein report a case of small intestinal bleeding of AVM successfully treated with double-balloon enteroscopy (DBE) and laparoscope-assisted resection. A 44-year-old man complained of hematochezia and visited the previous doctor. He underwent gastroscopy and colonoscopy, but no bleeding site was detected. However, he rebled 2 days later and became hypotensive. Abdominal computed tomography revealed a hypervascular nodule in the jejunum. He was transferred to our institution for further treatment. DBE was performed and revealed a small pulsatile lesion with a tiny mucosal break. We then injected a marking tattoo. Two days later, he underwent an operation. We were able to easily locate the tattooed lesion laparoscopically and performed jejunal partial resection. His postoperative course was uneventful. DBE enabled a precise diagnosis and minimal invasive surgery.
Online Screening and Personalized Education to Identify Post-Deployment Mental Health Need and Facilitate Access to Care
Authors: Mengeling Michelle A , Torner James C , Smith Jeffrey L , Cook Brian L , Sadler Anne G
Published: December 2022

Introduction

Reserve and National Guard (RNG) service members face increased risks for psychological and behavioral problems and are unlikely to seek mental health (MH) care after returning from military deployments. This article examines an online intervention (Web-Ed) with regard to participation, screening results, satisfaction, and intent to seek follow-up MH care, with comparisons by gender and post-deployment MH care receipt.

Materials and Methods

This was a cross-sectional study of 414 RNG service members (214 women and 200 men), who returned from deployments to or in support of the Iraq or Afghanistan wars within the prior 36 months. Participants completed Web-Ed, which includes screening, personalized education, and links to Veterans Health Administration health care.

Results

Positive post-deployment screening proportions, Web-Ed satisfaction, and intent to seek follow-up care were similar for men and women. Few had received MH care (33% women; 24% men), yet most screened positive on at least one screen (69% women; 72% men). Most indicated that they would recommend Web-Ed to other veterans (71% women; 67% men) and that they received useful information they may not have received otherwise (52% women; 53% men) regardless of gender or prior MH care. Almost half (40% women; 48% men) planned to seek further assessment from a health care provider as a direct result of Web-Ed.

Conclusions

Efforts to facilitate access to MH care among post-deployed RNG veterans should be ongoing, regardless of the length of time since deployment, Veterans Affairs enrollment status, prior MH care receipt, or gender. Online screening and personalized education engage veterans who have not sought MH care and provide new information to those who have.
Prospects for detecting transient quasi-monochromatic gravitational waves from glitching pulsars with current and future detectors
Authors: Moragues Joan , Modafferi Luana M , Tenorio Rodrigo , Keitel David
Published: December 2022

Pulsars are rotating neutron stars that emit periodic electromagnetic radiation. While pulsars generally slow down as they lose energy, some also experience glitches: spontaneous increases of their rotational frequency. According to several models, these glitches can also lead to the emission of long-duration transient gravitational waves (GWs). We present detection prospects for such signals by comparing indirect energy upper limits on GW strain for known glitches with the sensitivity of current and future ground-based GW detectors. We first consider the optimistic case of generic constraints based on the glitch size and find that realistic matched-filter searches in the fourth LIGO–Virgo–KAGRA observing run (O4) could make a detection, or set constraints below these indirect upper limits, for equivalents of 36 out of 726 previously observed glitches, and 74 in the O5 run. With the third-generation Einstein Telescope or Cosmic Explorer, 35–40 per cent of glitches would be accessible. When specializing to a scenario where transient mountains produce the post-glitch GW emission, following the Yim & Jones model, the indirect upper limits are stricter. Out of the smaller set of 119 glitches with measured healing parameter, as needed for predictions under that model, only 6 glitches would have been within reach for O4 and 14 for O5, with a similar percentage as before with third-generation detectors. We also discuss how this model matches the observed glitch population.
A search for variable subdwarf B stars in TESS Full Frame Images III. An update on variable targets in both ecliptic hemispheres – contamination analysis and new sdB pulsators
Authors: Sahoo S K , Baran A S , Worters H L , Németh P , Kilkenny D
Published: December 2022

We present an update on the variable star survey performed on the TESS 30 min Full Frame Image (FFI) data reported by our first two papers in this series. This update includes a contamination analysis in order to identify false positives and analysis of the TESS 10 min FFI data collected during Years 3 and 4 of the mission. We clarify the variability status of 2 995 targets identifying 1 403 variable stars. In addition, we spectroscopically classify 24 pre-filtered targets sampled with the 10 min FFI data and discover 11 new sdB pulsators. Future follow-up space- and/or ground-based data of variables reported here, to identify the nature of their variability and reveal spectroscopic parameters of the stars, would complement this work.
Model selection using time-delay lenses
Authors: Melia Fulvio , Wei Jun-Jie , Wu Xue-Feng
Published: December 2022

The sample of time-delay gravitational lenses appropriate for studying the geometry of the Universe continues to grow as dedicated campaigns, such as the Dark Energy Survey, the (Very Large Telescope) VLT Survey Telescope (VST) ATLAS survey, and the Large Synoptic Survey Telescope, complete their census of high-redshift sources. This catalogue now includes hundreds of strong lensing systems, at least 31 of which have reasonably accurate time-delay measurements. In this paper, we use them to compare the predictions of two competing Friedmann–Lemaître–Robertson–Walker models: flat Lambda cold dark matter (ΛCDM), characterized by two adjustable parameters (H0 and Ωm), and the Rh = ct universe (with H0 as the single free variable). Over the past decade, the latter has accounted for the data better than the standard model, most recently the emergence of well-formed galaxies discovered by JWST at cosmic dawn. Here, we show that the current sample of time-delay lenses favours Rh = ct with a likelihood of ∼$84{{\ \rm per\ cent}}$ versus ∼$16{{\ \rm per\ cent}}$ for the standard model. This level of accuracy will greatly improve as the ongoing surveys uncover many thousands of additional lens systems over the next several years.
CRISPRi-based programmable logic inverter cascade for antibiotic-free selection and maintenance of multiple plasmids
Authors: Kim Seong Keun , Kim Haseong , Woo Seung Gyun , Kim Tae Hyun , Rha Eugene , Kwon Kil Koang , Lee Hyewon , Lee Seung-Goo , Lee Dae-Hee
Published: December 2022

Antibiotics have been widely used for plasmid-mediated cell engineering. However, continued use of antibiotics increases the metabolic burden, horizontal gene transfer risks, and biomanufacturing costs. There are limited approaches to maintaining multiple plasmids without antibiotics. Herein, we developed an inverter cascade using CRISPRi by building a plasmid containing a single guide RNA (sgRNA) landing pad (pSLiP); this inhibited host cell growth by repressing an essential cellular gene. Anti-sgRNAs on separate plasmids restored cell growth by blocking the expression of growth-inhibitory sgRNAs in pSLiP. We maintained three plasmids in Escherichia coli with a single antibiotic selective marker. To completely avoid antibiotic use and maintain the CRISPRi-based logic inverter cascade, we created a novel d-glutamate auxotrophic E. coli. This enabled the stable maintenance of the plasmid without antibiotics, enhanced the production of the terpenoid, (−)-α-bisabolol, and generation of an antibiotic-resistance gene-free plasmid. CRISPRi is therefore widely applicable in genetic circuits and may allow for antibiotic-free biomanufacturing.
Genome-scale top-down strategy to generate viable genome-reduced phages
Authors: Yuan Shengjian , Shi Juan , Jiang Jianrong , Ma Yingfei
Published: December 2022

Efforts have been made to reduce the genomes of living cells, but phage genome reduction remains challenging. It is of great interest to investigate whether genome reduction can make phages obtain new infectious properties. We developed a CRISPR/Cas9-based iterative phage genome reduction (CiPGr) approach and applied this to four distinct phages, thereby obtaining heterogeneous genome-reduced mutants. We isolated and sequenced 200 mutants with loss of up to 8–23% (3.3–35 kbp) of the original sequences. This allowed the identification of non-essential genes for phage propagation, although loss of these genes is mostly detrimental to phage fitness to various degrees. Notwithstanding this, mutants with higher infectious efficiency than their parental strains were characterized, indicating a trade-off between genome reduction and infectious fitness for phages. In conclusion, this study provides a foundation for future work to leverage the information generated by CiPGr in phage synthetic biology research.
Changes in outcomes and factors associated with survival in melanoma patients with brain metastases
Authors: Hasanov Merve , Milton Denái R , Davies Alicia Bea , Sirmans Elizabeth , Saberian Chantal , Posada Eliza L , Opusunju Sylvia , Gershenwald Jeffrey E , Torres-Cabala Carlos A , Burton Elizabeth M , Colen Rivka R , Huse Jason T , Glitza Oliva Isabella C , Chung Caroline , McAleer Mary Frances , McGovern Susan L , Yeboa Debra N , Kim Betty Y S , Prabhu Sujit S , McCutcheon Ian E , Weinberg Jeffrey S , Lang Frederick F , Tawbi Hussein A , Li Jing , Haydu Lauren E , Davies Michael A , Ferguson Sherise D
Published: December 2022

Background

Treatment options for patients with melanoma brain metastasis (MBM) have changed significantly in the last decade. Few studies have evaluated changes in outcomes and factors associated with survival in MBM patients over time. The aim of this study is to evaluate changes in clinical features and overall survival (OS) for MBM patients.

Methods

Patients diagnosed with MBMs from 1/1/2009 to 12/31/2013 (Prior Era; PE) and 1/1/2014 to 12/31/2018 (Current Era; CE) at The University of Texas MD Anderson Cancer Center were included in this retrospective analysis. The primary outcome measure was OS. Log-rank test assessed differences between groups; multivariable analyses were performed with Cox proportional hazards models and recursive partitioning analysis (RPA).

Results

A total of 791 MBM patients (PE, n = 332; CE, n = 459) were included in analysis. Median OS from MBM diagnosis was 10.3 months (95% CI, 8.9–12.4) and improved in the CE vs PE (14.4 vs 10.3 months, P < .001). Elevated serum lactate dehydrogenase (LDH) was the only factor associated with worse OS in both PE and CE patients. Factors associated with survival in CE MBM patients included patient age, primary tumor Breslow thickness, prior immunotherapy, leptomeningeal disease, symptomatic MBMs, and whole brain radiation therapy. Several factors associated with OS in the PE were not significant in the CE. RPA demonstrated that elevated serum LDH and prior immunotherapy treatment are the most important determinants of survival in CE MBM patients.

Conclusions

OS and factors associated with OS have changed for MBM patients. This information can inform contemporary patient management and clinical investigations.
A universal training scheme and the resulting universality for machine learning phases
Authors: Tseng Yuan-Heng , Jiang Fu-Jiun , Huang C-Y
Published: December 2022

An autoencoder (AE) and a generative adversarial network (GAN) are trained only once on a one-dimensional (1D) lattice of 200 sites. Moreover, the AE contains only one hidden layer consisting of two neurons, and both the generator and the discriminator of the GAN are made up of two neurons as well. The training set employed to train both the considered unsupervised neural networks (NNs) is composed of two artificial configurations. Remarkably, despite their simple architectures, both the built AE and GAN have precisely determined the critical points of several models, including the three-dimensional classical O(3) model, the two-dimensional generalized classical XY model, the two-dimensional two-state Potts model, and the one-dimensional Bose–Hubbard model. In addition, a factor of several thousands in the speed of calculation is gained for the built AE and GAN when they are compared with the conventional unsupervised NN approaches. The results presented here, as well as those shown previously in the literature, suggest that when phase transitions are considered, an elegant universal neural network that is extremely efficient and is applicable to broad physical systems can be constructed with ease. In particular, since an NN trained with two configurations can be applied to many models, it is likely that when machine learning is concerned, the majority of phase transitions belong to a class having two elements, i.e. the Ising class.
Impact of COVID-19 pandemic on the management of patients with RA: a survey of rheumatologists in six European countries
Authors: Machado Pedro M , Verschueren Patrick , Grainger Rebecca , Jones Hannah , Piercy James , van Beneden Katrien , Caporali Roberto , Dejaco Christian , Fautrel Bruno
Published: December 2022

Objective

We aimed to describe, from the perspective of rheumatologists in Europe, how the coronavirus disease 2019 (COVID-19) pandemic has impacted their management of people with RA and the continuing medical education of physicians.

Methods

Rheumatologists participating in the Adelphi RA Disease Specific ProgrammeTM in six European countries were contacted in August and September 2020 for a telephone survey. Rheumatologists were asked seven attitudinal questions on changes to patient management, prescription behaviour and continuing education owing to COVID-19. Results were summarized with descriptive statistics.

Results

The telephone survey was completed by 284 rheumatologists. The most commonly reported changes to patient management were increased utilization of video/telephone consultations (66.5% of respondents), fewer visits (58.5%) and limiting physical contact (58.1%). Furthermore, 67.9% of rheumatologists who indicated that prescribing behaviour had changed switched their patients to self-administered medication, and 60.7% reported not starting patients on targeted synthetic DMARDs, biologic originator DMARDs or biosimilar DMARDs. In total, 57.6% of rheumatologists believed that changes in management would persist. Rheumatologists reported that 38.0% of patients expressed concerns about how COVID-19 would impact treatment, including access to treatment and the risk of infection. The biggest impact on rheumatologist education was a switch to online training and conferences.

Conclusion

All countries saw changes in patient management and prescribing behaviour, including the rapid uptake of telemedicine. It is important that the international rheumatology community learns from these experiences to prepare better for future pandemics and to address ongoing rheumatologist shortages.
Modified fibrin hydrogel for sustained delivery of RNAi lipopolyplexes in skeletal muscle
Authors: Ngarande Ellen , Doubell Emma , Tamgue Ousman , Mano Manuel , Human Paul , Giacca Mauro , Davies Neil Hamer
Published: December 2022

RNA interference is a promising therapeutical approach presently hindered by delivery concerns such as rapid RNA degradation and targeting of individual tissues. Injectable hydrogels are one potentially simple and direct route towards overcoming these barriers. Here we report on the utility of a combination of a mildly modified form of the clinically utilised fibrin hydrogel with Invivofectamine® 3.0, a lipid nonviral transfection vector, for local and sustained release. PEGylation of fibrin allowed for controlled release of small interfering RNA (siRNA)-lipopolyplexes for at least 10 days and greatly increased the stability of fibrin in vitro and in vivo. A 3D cell culture model and a release study showed transfection efficacy of siRNA-lipopolyplexes was retained for a minimum of 7 days. Injection in conjunction with PEGylated-fibrinogen significantly increased retention of siRNA-lipopolyplexes in mouse skeletal muscle and enhanced knockdown of myostatin mRNA that correlated with muscle growth. Thus, the increased efficacy observed here for the combination of a lipid nanoparticle, the only type of nonviral vector approved for the clinic, with fibrin, might allow for more rapid translation of injectable hydrogel-based RNA interference.
The Eleventh-Century ‘N’ Psalter from England: New Pieces of the Puzzle
Authors: Opalińska Monika , Pludra-Żuk Paulina , Chlebus Ewa
Published: December 2022

This paper presents an analysis of two recently found fragments of a Latin psalter with a continuous Old English gloss. The fragments were used as endleaf guards in an early modern book from the collection of Samuel Meienreis, currently held at the C. Norwid Library in Elbląg. We argue that the newly found parchment pieces match four other membra disiecta from the same eleventh-century codex produced in England. Since the formerly identified fragments were removed from the bindings of unknown books, their provenance and the origin of the manuscript from which they were removed have not been established, so far. The new findings partially fill this gap. In this paper we explore palaeographical and linguistic evidence, and the historical context of the manuscript waste found in Elbląg in an attempt to reconstruct the history of the so-called N Psalter to which all the extant pieces once belonged.
Hazed and Confused: The Effect of Air Pollution on Dementia
Authors: Bishop Kelly C , Ketcham Jonathan D , Kuminoff Nicolai V
Published: December 2022

We study whether long-term cumulative exposure to airborne small particulate matter (PM2.5) affects the probability that an individual receives a new diagnosis of Alzheimer's disease or related dementias. We track the health, residential location, and PM2.5 exposures of Americans aged sixty-five and above from 2001 through 2013. The expansion of Clean Air Act regulations led to quasi-random variation in individuals’ subsequent exposures to PM2.5. We leverage these regulations to construct instrumental variables for individual-level decadal PM2.5 that we use within flexible probit models that also account for any potential sample selection based on survival. We find that a 1 µg/m3 increase in decadal PM2.5 increases the probability of a new dementia diagnosis by an average of 2.15 percentage points (pp). All else equal, we find larger effects for women, older people, and people with more clinical risk factors for dementia. These effects persist below current regulatory thresholds.
Serum IFNα2 levels are associated with disease activity and outperform IFN-I gene signature in a longitudinal childhood-onset SLE cohort
Authors: Wahadat M Javad , Qi Hongchao , van Helden-Meeuwsen Cornelia G , Huijser Erika , van den Berg Lotte , van Dijk-Hummelman Annette , Göpfert Jens C , Heine Anne , Verkaaik Marleen , Schreurs Marco W J , Dik Willem A , Kamphuis Sylvia , Versnel Marjan A
Published: December 2022

Objective

To study the association of serum IFNα2 levels measured by ultrasensitive single-molecule array (Simoa) and the IFN-I gene signature (IGS) with disease activity and determine whether these assays can mark disease activity states in a longitudinal cohort of childhood-onset SLE (cSLE) patients.

Methods

Serum IFNα2 levels were measured in 338 samples from 48 cSLE patients and 67 healthy controls using an IFNα Simoa assay. Five-gene IGS was measured by RT-PCR in paired whole blood samples. Disease activity was measured by clinical SELENA-SLEDAI and BILAG-2004. Low disease activity was defined by Low Lupus Disease Activity State (LLDAS) and flares were characterized by SELENA-SLEDAI flare index. Analysis was performed using linear mixed models.

Results

A clear positive correlation was present between serum IFNα2 levels and the IGS (r = 0.78, P < 0.0001). Serum IFNα2 levels and IGS showed the same significant negative trend in the first 3 years after diagnosis. In this timeframe, mean baseline serum IFNα2 levels decreased by 55.1% (Δ 201 fg/ml, P < 0.001) to a mean value of 164 fg/ml, which was below the calculated threshold of 219.4 fg/ml that discriminated between patients and healthy controls. In the linear mixed model, serum IFNα2 levels were significantly associated with both cSELENA-SLEDAI and BILAG-2004, while the IGS did not show this association. Both IFN-I assays were able to characterize LLDAS and disease flare in receiver operating characteristic analysis.

Conclusions

Serum IFNα2 levels measured by Simoa technology are associated with disease activity scores and characterize disease activity states in cSLE.
Atypical hypnotic compound ML297 restores sleep architecture immediately following emotionally valenced learning, to promote memory consolidation and hippocampal network activation during recall
Authors: Martinez Jessy D , Brancaleone William P , Peterson Kathryn G , Wilson Lydia G , Aton Sara J
Published: December 2022

Sleep plays a critical role in consolidating many forms of hippocampus-dependent memory. While various classes of hypnotic drugs have been developed in recent years, it remains unknown whether, or how, some of them affect sleep-dependent memory consolidation mechanisms. We find that ML297, a recently developed candidate hypnotic agent targeting a new mechanism (activating GIRK1/2-subunit containing G-protein coupled inwardly rectifying potassium [GIRK] channels), alters sleep architecture in mice over the first 6 hr following a single-trial learning event. Following contextual fear conditioning (CFC), ML297 reversed post-CFC reductions in NREM sleep spindle power and REM sleep amounts and architecture, renormalizing sleep features to what was observed at baseline, prior to CFC. Renormalization of post-CFC REM sleep latency, REM sleep amounts, and NREM spindle power were all associated with improved contextual fear memory (CFM) consolidation. We find that improvements in CFM consolidation due to ML297 are sleep-dependent, and are associated with increased numbers of highly activated dentate gyrus (DG), CA1, and CA3 neurons during CFM recall. Together our findings suggest that GIRK1/2 channel activation restores normal sleep architecture— including REM sleep, which is normally suppressed following CFC—and increases the number of hippocampal neurons incorporated into the CFM engram during memory consolidation.
ETV2 Upregulation Marks the Specification of Early Cardiomyocytes and Endothelial Cells During Co-differentiation
Authors: Cao Xu , Mircea Maria , Yakala Gopala Krishna , van den Hil Francijna E , Brescia Marcella , Mei Hailiang , Mummery Christine L , Semrau Stefan , Orlova Valeria V
Published: December 2022

The ability to differentiate human-induced pluripotent stem cells (hiPSCs) efficiently into defined cardiac lineages, such as cardiomyocytes and cardiac endothelial cells, is crucial to study human heart development and model cardiovascular diseases in vitro. The mechanisms underlying the specification of these cell types during human development are not well understood which limits fine-tuning and broader application of cardiac model systems. Here, we used the expression of ETV2, a master regulator of hematoendothelial specification in mice, to identify functionally distinct subpopulations during the co-differentiation of endothelial cells and cardiomyocytes from hiPSCs. Targeted analysis of single-cell RNA-sequencing data revealed differential ETV2 dynamics in the 2 lineages. A newly created fluorescent reporter line allowed us to identify early lineage-predisposed states and show that a transient ETV2-high-state initiates the specification of endothelial cells. We further demonstrated, unexpectedly, that functional cardiomyocytes can originate from progenitors expressing ETV2 at a low level. Our study thus sheds light on the in vitro differentiation dynamics of 2 important cardiac lineages.
Cacao Swollen Shoot Viruses in Ghana
Authors: Gyamera Ebenezer Antwi , Domfeh Owusu , Ameyaw George Akumfi
Published: December 2022

Cacao swollen shoot virus causes cacao swollen shoot disease of Theobroma cacao (cacao) plants. At least six cacao-infecting Badnavirus species—Cacao swollen shoot Togo A virus, Cacao swollen shoot Togo B virus (previously known as Cacao swollen shoot virus), Cacao swollen shoot CE virus, Cacao swollen shoot Ghana M virus, Cacao swollen shoot Ghana N virus, and Cacao swollen shoot Ghana Q virus—are responsible for the swollen shoot disease of cacao in Ghana. Each of these species consists of a multiplicity of strains. The New Juaben strain, the most virulent cacao swollen shoot virus strain in Ghana, belongs to the Cacao swollen shoot Togo B virus species, and is a commonly used strain in laboratory transmission assays. Infection of cacao trees with multiple strains of the virus is common and new evidence suggests that these coinfections may have resulted in the emergence of recombinant strains of the virus. The impact of these emerging recombinant strains on disease severity is uncertain. This review focuses largely on the discovery of cacao swollen shoot virus in Ghana, diversity of the virus strains, molecular characterization, propagation of virus infection in cacao plants, emergence of recombinant virus strains, vector-mediated transmission of the virus, and the management of the cacao swollen shoot disease in Ghana. It also contains sections on the botany and origin of the cacao tree, its introduction to Ghana, the role of cacao swollen shoot disease in facilitating Ghana’s independence from Britain, and a brief history of chocolate.
“The Feeling of Failure Is Immense”: A Qualitative Analysis of the Experiences of Unmatched Residency Applicants Using Reddit
Authors: Morrissette Anita , Morrissette Matthew
Published: December 2022

Purpose

The increasing number of applicants who do not match to a residency program has been identified as an issue in Canada and the United States, yet the experiences of those individuals going unmatched have remained largely unexplored. By better understanding such experiences, medical schools will be better equipped to support unmatched graduates. The authors sought to understand the shared experiences of unmatched residency applicants, including those who did not match to American residency programs.

Method

The authors turned to the social media platform Reddit as their source of data to further understand the experiences of unmatched residency applicants, using a thematic analysis of comments posted on the subreddit r/medicalschool. The subreddit was searched for comments containing the term unmatched on August 16, 2021. A total of 206 comments containing content about first-person experiences of going unmatched were included in the thematic analysis.

Results

The 206 comments were authored by 124 unique usernames between the years of 2012 and 2021. Two primary themes emerged in the analysis: perceptions of insufficient return for investments made in medical education and concern about the possibility of going unmatched again in the future. Subthemes identified for the first theme were regret for pursuing medical school, perceptions of failure, and considering an alternative career. Subthemes identified for the second theme were perceived lack of transparency and fairness in the match process and desire to improve future applications, which sometimes involved considering applying to other specialties.

Conclusions

The results of this study suggest unmatched applicants are prone to a range of negative cognitive and emotional reactions. In light of these findings, medical schools should ensure effective supports are being offered to unmatched applicants in a timely and nonjudgmental manner. Future work should focus on investigating the outcomes of interventions for supporting unmatched applicants.