bluuebunny/crossref_metadata_2025 huggingface dataset:
Two-dimensional silicon nanomaterials for optoelectronics
Authors: Deng Xuebiao , Chen Huai , Yang Zhenyu
Published: April 2023

Silicon nanomaterials have been of immense interest in the last few decades due to their remarkable optoelectronic responses, elemental abundance, and higher biocompatibility. Two-dimensional silicon is one of the new allotropes of silicon and has many compelling properties such as quantum-confined photoluminescence, high charge carrier mobilities, anisotropic electronic and magnetic response, and non-linear optical properties. This review summarizes the recent advances in the synthesis of two-dimensional silicon nanomaterials with a range of structures (silicene, silicane, and multilayered silicon), surface ligand engineering, and corresponding optoelectronic applications.
A family of flexible two-dimensional semiconductors: MgMX2Y6 (M = Ti/Zr/Hf; X = Si/Ge; Y = S/Se/Te)
Authors: Yuan Junhui , Xue Kanhao , Miao Xiangshui , Ye Lei
Published: April 2023

Inspired by the recently predicted 2D MX2Y6 (M = metal element; X = Si/Ge/Sn; Y = S/Se/Te), we explore the possible applications of alkaline earth metal (using magnesium as example) in this family based on the idea of element replacement and valence electron balance. Herein, we report a new family of 2D quaternary compounds, namely MgMX2Y6 (M = Ti/Zr/Hf; X = Si/Ge; Y = S/Se/Te) monolayers, with superior kinetic, thermodynamic and mechanical stability. In addition, our results indicate that MgMX2Y6 monolayers are all indirect band gap semiconductors with band gap values ranging from 0.870 to 2.500 eV. Moreover, the band edges and optical properties of 2D MgMX2Y6 are suitable for constructing multifunctional optoelectronic devices. Furthermore, for comparison, the mechanical, electronic and optical properties of In2X2Y6 monolayers have been discussed in detail. The success of introducing Mg into the 2D MX2Y6 family indicates that more potential materials, such as Ca- and Sr-based 2D MX2Y6 monolayers, may be discovered in the future. Therefore, this work not only broadens the existing family of 2D semiconductors, but it also provides beneficial results for the future.
Entanglement witness and multipartite quantum state discrimination
Authors: Ha Donghoon , Kim Jeong San
Published: April 2023

We consider multipartite quantum state discrimination and show that the minimum-error discrimination by separable measurements is closely related to the concept of entanglement witness (EW). Based on the properties of EW, we establish some necessary and/or sufficient conditions on minimum-error discrimination by separable measurements. We also provide some conditions on the upper bound of the maximum success probability over all possible separable measurements. Our results are illustrated by examples of multidimensional multipartite quantum states. Finally, we provide a systematic way in terms of the EW to construct multipartite quantum state ensembles showing nonlocality in state discrimination.
Characteristics of 1D ordered arrays of optical centers in solid-state photonics
Authors: Kling Trevor , Hosseini Mahdi
Published: April 2023

Collective interaction of emitter arrays has lately attracted significant attention due to its role in controlling directionality of radiation, spontaneous emission and coherence. We focus on light interactions with engineered arrays of solid-state emitters in photonic resonators. We theoretically study light interaction with an array of emitters or optical centers embedded inside a microring resonator and discuss its application in the context of solid-state photonic systems. We discuss how such arrays can be experimentally realized and how the inhomogeneous broadening of mesoscopic atomic arrays can be leveraged to study broadband collective excitations in the array.
Probabilistic behavioral distance and tuning—reducing and aggregating complex systems
Authors: Hellmann Frank , Zolotarevskaia Ekaterina , Kurths Jürgen , Raisch Jörg
Published: April 2023

Given two dynamical systems, we quantify how similar they are with respect to their interaction with the outside world. We focus on the case where simpler systems act as a specification for a more complex one. Combining a behavioral and probabilistic perspective we define several useful notions of the distance of a system to a specification. We show that these distances can be used to tune a complex system. We demonstrate that our approach can successfully make non-linear networked systems behave like much smaller networks, allowing us to aggregate large sub-networks into one or two effective nodes. Finally, we discuss similarities and differences between our approach and

H
∞

model reduction.
Initial state reconstruction on graphs
Authors: Khoa Vo , Truong Mai , Hogan Imhotep , Williams Roselyn
Published: April 2023

The presence of noise is an intrinsic problem in acquisition processes for digital images. One way to enhance images is to combine the forward and backward diffusion equations. However, the latter problem is well known to be exponentially unstable with respect to any small perturbations on the final data. In this scenario, the final data can be regarded as a blurred image obtained from the forward process, and that image can be pixelated as a network. Therefore, we study in this work a regularization framework for the backward diffusion equation on graphs. Our aim is to construct a spectral graph-based solution based upon a cut-off projection. Stability and convergence results are provided together with some numerical experiments.
HPV Cotesting of Unsatisfactory Papanicolaou Tests: Implications for Follow-up Intervals
Authors: Chen Fei , Hsu Lin Lawrence , Hindi Issa , Sun Wei , Shafizadeh Negin , Szeto Oliver , Brandler Tamar C , Simsir Aylin
Published: April 2023

Objectives

The 2019 American Society of Colposcopy and Cervical Pathology management guidelines recommend that patients with an unsatisfactory Papanicolaou (Pap) test (UPT) and negative human papillomavirus (HPV) cotest undergo repeat age-based screening in 2 to 4 months. The rationale is that a negative HPV test in the setting of an UPT may reflect an inadequate sample and therefore should not be interpreted as truly “negative.” For patients 25 years and older who are cotested, if HPV is positive for the 16 or 18 genotypes, direct referral for colposcopy is recommended. Our study aimed to determine if a negative HPV cotest result is predictive of the absence of a high-grade squamous intraepithelial lesion (HSIL) and whether these patients may be called back for repeat testing at an interval longer than 2 to 4 months.

Methods

Follow-up cervical cytology and biopsy results in women with UPT and HPV cotests from January 2017 to December 2021 were collected. Original UPT and HPV cotest results were correlated with the follow-up Pap and biopsy results.

Results

There were 1,496 (2.28%) UPT cases out of 65,641 total Pap tests. Among the 1,496 UPT cases, 1,010 (67.5%) had HPV cotesting; 676 (45.1%) were followed by repeat Pap or biopsy within 4 months and 850 (56.8%) within 12 months. The total follow-up rate was 81%, with a range of 3 days to 36 months. The HSIL rate in HPV-positive cases was 5.7% (3/53) vs 0.4% (2/539) (P = .006) in HPV-negative cases. In UPT, HPV cotesting showed negative predictive values for low-grade and high-grade squamous intraepithelial lesion detection of 98.5% and 99.6%, respectively, while positive predictive values were 19% and 5.7%.

Conclusions

A negative HPV cotest in individuals with UPT predicted the lack of HSIL in our study. Compliance with the recommended follow-up time of 2 to 4 months for women with UPT was low (45.1%). Our study suggests that women with UPT and negative HPV cotest may be safely called back at an interval longer than 4 months.
Multiorgan Involvement of Dormant Uveal Melanoma Micrometastases in Postmortem Tissue From Patients Without Coexisting Macrometastases
Authors: Gill Viktor T , Norrman Emelie , Sabazade Shiva , Karim Ali , Lardner Emma , Stålhammar Gustav
Published: April 2023

Objectives

Almost half of all patients diagnosed with uveal melanoma will die of metastatic disease. This has been attributed to early seeding of micrometastases. We investigate the presence, density, organ involvement, and characteristics of micrometastases of uveal melanoma in tissue obtained at autopsy of patients with and without coexisting macrometastases.

Methods

Patients diagnosed with primary uveal melanoma at a national referral center between 1960 and 2020 (n = 4,282) were cross-referenced with autopsy registers at nearby hospitals. Eleven patients were included. Formalin-fixed, paraffin-embedded tissue samples obtained during autopsy were examined with routine histology, immunohistochemistry, and immunomagnetic separation.

Results

Micrometastases were detected in 5 of 5 patients with and in 5 of 6 patients without coexisting macrometastases. Micrometastases were identified in several sites, including lungs, kidneys, myocardium, and bone marrow. Their highest density per mm2 of tissue was seen in the liver. Of 11 examined patients, 2 had at least 1 BAP-1–positive metastasis. All micrometastases had immune cell infiltrates and no or very low proliferative activity.

Conclusions

We demonstrate multiorgan involvement of apparently dormant micrometastases in patients with uveal melanoma. This suggests that micrometastases are present in nearly all patients diagnosed with primary uveal melanoma, regardless of coexisting macrometastases.
Residency application content and considerations based on residency director review of a fictitious CV: What really matters?
Authors: Pate Adam N , Mills Alex R , Fleming Joshua W , Phan Ha K , Street Margaret , Pitcock James J
Published: April 2023

Purpose

This research was conducted to evaluate the influence of a pharmacy residency candidate’s prior work or research experience on the potential for selection for an interview. Additionally, residency program directors (RPDs) were asked to evaluate the importance of letters of intent and recommendation, rank the importance of typical curriculum vitae (CV) items along with general preferences, and provide advice for a standout CV.

Methods

This cross-sectional, survey-based study recruited RPDs to review a work-focused or research-focused fictitious residency candidate CV and complete a 33-question survey regarding interest in interviewing the fictitious candidate and their general perceptions of significant factors in interview candidate selection.

Results

A total of 456 RPDs responded to the survey, with 229 respondents assigned to evaluate the work-focused CV and 227 assigned to review the research-focused CV. Among RPDs who provided CV evaluations, 81.2% (147/181) of those who reviewed the research-focused CV and 78.3% (137/175) of those who reviewed the work-focused CV gave a positive evaluation (P > 0.05). Work experience and extracurricular activities were considered the most important CV sections, and high-quality advanced pharmacy practice experience (APPE) rotations and pharmacy work experience were perceived to have the highest correlation with success in residency.

Conclusion

This work supports the importance of candidates creating a well-rounded CV in preparing themselves for residency. Pharmacy-related work experience and high-quality APPE rotations seem to be key in an RPD’s opinions of predicted success in a residency program. The CV remains a vital document in the residency candidate review process, and it deserves a high degree of effort in ensuring it adequately reflects professional experiences.
nestedcv: an R package for fast implementation of nested cross-validation with embedded feature selection designed for transcriptomics and high-dimensional data
Authors: Lewis Myles J , Spiliopoulou Athina , Goldmann Katriona , Pitzalis Costantino , McKeigue Paul , Barnes Michael R
Published: April 2023

Motivation

Although machine learning models are commonly used in medical research, many analyses implement a simple partition into training data and hold-out test data, with cross-validation (CV) for tuning of model hyperparameters. Nested CV with embedded feature selection is especially suited to biomedical data where the sample size is frequently limited, but the number of predictors may be significantly larger (P ≫ n).

Results

The nestedcv R package implements fully nested k × l-fold CV for lasso and elastic-net regularized linear models via the glmnet package and supports a large array of other machine learning models via the caret framework. Inner CV is used to tune models and outer CV is used to determine model performance without bias. Fast filter functions for feature selection are provided and the package ensures that filters are nested within the outer CV loop to avoid information leakage from performance test sets. Measurement of performance by outer CV is also used to implement Bayesian linear and logistic regression models using the horseshoe prior over parameters to encourage a sparse model and determine unbiased model accuracy.

Availability and implementation

The R package nestedcv is available from CRAN: https://CRAN.R-project.org/package=nestedcv.
Structure-aware protein self-supervised learning
Authors: Chen Can (Sam) , Zhou Jingbo , Wang Fan , Liu Xue , Dou Dejing
Published: April 2023

Motivation

Protein representation learning methods have shown great potential to many downstream tasks in biological applications. A few recent studies have demonstrated that the self-supervised learning is a promising solution to addressing insufficient labels of proteins, which is a major obstacle to effective protein representation learning. However, existing protein representation learning is usually pretrained on protein sequences without considering the important protein structural information.

Results

In this work, we propose a novel structure-aware protein self-supervised learning method to effectively capture structural information of proteins. In particular, a graph neural network model is pretrained to preserve the protein structural information with self-supervised tasks from a pairwise residue distance perspective and a dihedral angle perspective, respectively. Furthermore, we propose to leverage the available protein language model pretrained on protein sequences to enhance the self-supervised learning. Specifically, we identify the relation between the sequential information in the protein language model and the structural information in the specially designed graph neural network model via a novel pseudo bi-level optimization scheme. We conduct experiments on three downstream tasks: the binary classification into membrane/non-membrane proteins, the location classification into 10 cellular compartments, and the enzyme-catalyzed reaction classification into 384 EC numbers, and these experiments verify the effectiveness of our proposed method.

Availability and implementation

The Alphafold2 database is available in https://alphafold.ebi.ac.uk/. The PDB files are available in https://www.rcsb.org/. The downstream tasks are available in https://github.com/phermosilla/IEConv\_proteins/tree/master/Datasets. The code of the proposed method is available in https://github.com/GGchen1997/STEPS_Bioinformatics.
A case of Paederus dermatitis in Western Europe: a signal for a One Health–One World concept for the dermatologist
Authors: Descatha Alexis , Ezzedine Khaled , Le Roux Gael
Published: April 2023

This reported case of Paederus dermatitis in Western Europe materializes the concept of One Health–One World to dermatologists. Although the condition is benign, the dermatologist should be aware of the diagnosis of Paederus dermatitis as global warming may lead to its spread in Western countries.
Basal ganglia functional connectivity network analysis does not support the ‘noisy signal’ hypothesis of Parkinson’s disease
Authors: Williams David
Published: April 2023

The ‘noisy signal’ hypothesis of basal ganglia dysfunction in Parkinson’s disease (PD) suggests that major motor symptoms of the disorder are caused by the development of abnormal basal ganglia activity patterns resulting in the propagation of ‘noisy’ signals to target systems. While such abnormal activity patterns might be useful biomarkers for the development of therapeutic interventions, correlation between specific changes in activity and PD symptoms has been inconsistently demonstrated, and raises questions concerning the accuracy of the hypothesis. Here, we tested this hypothesis by considering three nodes of the basal ganglia network, the subthalamus, globus pallidus interna, and cortex during self-paced and cued movements in patients with PD. Interactions between these regions were analyzed using measures that assess both linear and non-linear relationships. Marked changes in the network are observed with dopamine state. Specifically, we detected functional disconnection of the basal ganglia from the cortex and higher network variability in untreated PD, but various patterns of directed functional connectivity with lower network variability in treated PD. When we examine the system output, significant correlation is observed between variability in the cortico-basal ganglia network and muscle activity variability but only in the treated state. Rather than supporting a role of the basal ganglia in the transmission of noisy signals in patients with PD, these findings suggest that cortico-basal ganglia network interactions by fault or design, in the treated Parkinsonian state, are actually associated with improved cortical network output variability.
Cancer-associated fibroblasts-derived exosome-mediated transfer of miR-345-5p promotes the progression of colorectal cancer by targeting CDKN1A
Authors: Shi Weikun , Liu Yuxin , Qiu Xiaoyuan , Yang Ling , Lin Guole
Published: April 2023

Colorectal cancer (CRC) is the second leading cause of cancer-induced death in the world. Cancer-associated fibroblasts (CAFs) released exosomes that contributed to cancer progression. This research was carried out to study the influence of CRC-associated fibroblasts-derived exosomes on the phenotype of CRC cells and the underlying mechanism. CAFs-derived exosomes (CAFs-exo) and normal fibroblasts (NFs)-derived exosomes (NFs-exo) were recognized by transmission electronic microscopy, nanoparticle tracking analysis and western blot analysis. Cell counting kit-8, flow cytometry analysis, colony formation assay, Transwell, qRT-PCR, immunofluorescence, immunohistochemistry staining and xenografts model were carried out to proceed with function studies in vitro and in vivo. The results showed that CAFs-exo induced cell proliferation, migration and invasion, while NFs-exo did not influence the tumor biological properties of CRC cells. Using qRT-PCR, miR-345-5p was observed to be a notably up-regulated miRNA in CAFs-exo compared to NFs-exo. CAFs-exo could mediate the transfer of miR-345-5p to CRC cells, and downregulation of miR-345-5p in CAFs notably reversed the pro-tumoral effect of CAFs-exo on CRC cells. Based on online prediction database, CDKN1A was proved as a direct downstream target of miR-345-5p in CRC cells, which was lowly expressed and negatively associated with miR-345-5p in CRC tumors. Furthermore, miR-345-5p upregulation-mediated tumor biological behaviors were abrogated by exogenous CDKN1A. In CRC cells-beared tumor xenograft, CAFs-exo administration promoted tumor growth and decreased CDKN1A expression, whereas miR-345-5p inhibition reversed these effects. The present study revealed that by interacting with CDKN1A, CAF-derived exosomal miR-345-5p promotes CRC progression and metastasis.
Inhibition of lung adenocarcinoma by combinations of sulfasalazine (SAS) and disulfiram-copper (DSF-Cu) in cell line models and mice
Authors: Bagherpoor Alireza Jian , Shameem Mohammad , Luo Xianghua , Seelig Davis , Kassie Fekadu
Published: April 2023

Sulfasalazine (SAS) is a repurposed antitumor drug which inhibits the proliferation and survival of cancer cells by inhibiting the xCT cellular antioxidant system. Recent clinical studies have shown that, due to poor bioavailability, the antitumor effects of SAS monotherapy are minimal. Therefore, we hypothesized that DSF, another repurposed drug that has demonstrated anticancer effects, or its complex with copper (DSF-copper, DSF-Cu) could potentiate the antilung cancer effects of SAS. Exposure of non-small cell lung cancer cells to therapeutically achievable concentrations of SAS-induced low-to-moderate cytotoxic effects (20–40% reduction in cell viability) and, unexpectedly, induced the antioxidant protein NRF2 and its downstream effectors xCT and ALDH1A1. However, combinations of SAS and DSF-Cu, but not SAS and DSF, induced a significantly higher cytotoxic effect (64–88% reduction in cell viability), apoptosis and generation of mitochondrial reactive oxygen species as compared with SAS or DSF-Cu alone. Moreover, DSF-Cu abrogated SAS-induced NRF2, xCT and ALDH1A1 expression. In a mouse model of lung tumor, SAS + DSF-Cu showed a higher efficacy than the individual drugs in reducing the number and size of tumors as well as the incidence and multiplicity of lung adenocarcinoma. Taken together, our findings indicate that the observed antilung cancer effects of SAS plus DSF-Cu are mediated, at least in part, via impairment of reactive oxygen species defense and ­enhancement of oxidative stress and provide evidence for the preventive/therapeutic potential of this combinatorial approach against lung cancer.
High exposure to tacrolimus is associated with spontaneous remission of recurrent membranous nephropathy after kidney transplantation
Authors: Buxeda Anna , Caravaca-Fontán Fernando , Vigara Luis Alberto , Pérez-Canga José Luis , Calatayud Emma , Coloma Ana , Mazuecos Auxiliadora , Rodrigo Emilio , Sancho Asunción , Melilli Edoardo , Praga Manuel , Pérez-Sáez María José , Pascual Julio
Published: April 2023

Introduction

We aimed to characterize the incidence and clinical presentation of membranous nephropathy (MN) after kidney transplantation (KT), and to assess allograft outcomes according to proteinuria rates and immunosuppression management.

Methods

Multicenter retrospective cohort study including patients from six Spanish centers who received a KT between 1991–2019. Demographic, clinical, and histological data were collected from recipients with biopsy-proven MN as primary kidney disease (n = 71) or MN diagnosed de novo after KT (n = 4).

Results

Up to 25.4% of patients with biopsy-proven MN as primary kidney disease recurred after a median time of 18.1 months posttransplant, without a clear impact on graft survival. Proteinuria at 3-months post-KT was a predictor for MN recurrence (rMN, HR 4.28; P = 0.008). Patients who lost their grafts had higher proteinuria during follow-up [1.0 (0.5–2.5) vs 0.3 (0.1–0.5) g/24 h], but only eGFR after recurrence treatment predicted poorer graft survival (eGFR < 30 ml/min: RR = 6.8). We did not observe an association between maintenance immunosuppression and recurrence diagnosis. Spontaneous remission after rMN was associated with a higher exposure to tacrolimus before recurrence (trough concentration/dose ratio: 2.86 vs 1.18; P = 0.028). Up to 94.4% of KT recipients received one or several treatments after recurrence onset: 22.2% rituximab, 38.9% increased corticosteroid dose, and 66.7% ACEi/ARBs. Only 21 patients had proper antiPLA2R immunological monitoring.

Conclusions

One-fourth of patients with biopsy-proven MN as primary kidney disease recurred after KT, without a clear impact on graft survival. Spontaneous remission after rMN was associated with a higher exposure to tacrolimus before recurrence.
The circadian protein BMAL1 supports endothelial cell cycle during angiogenesis
Authors: Astone Matteo , Oberkersch Roxana E , Tosi Giovanni , Biscontin Alberto , Santoro Massimo M
Published: April 2023

Aims

The circadian clock is an internal biological timer that co-ordinates physiology and gene expression with the 24-h solar day. Circadian clock perturbations have been associated to vascular dysfunctions in mammals, and a function of the circadian clock in angiogenesis has been suggested. However, the functional role of the circadian clock in endothelial cells (ECs) and in the regulation of angiogenesis is widely unexplored.

Methods and results

Here, we used both in vivo and in vitro approaches to demonstrate that ECs possess an endogenous molecular clock and show robust circadian oscillations of core clock genes. By impairing the EC-specific function of the circadian clock transcriptional activator basic helix-loop-helix ARNT like 1 (BMAL1) in vivo, we detect angiogenesis defects in mouse neonatal vascular tissues, as well as in adult tumour angiogenic settings. We then investigate the function of circadian clock machinery in cultured EC and show evidence that BMAL and circadian locomotor output cycles protein kaput knock-down impair EC cell cycle progression. By using an RNA- and chromatin immunoprecipitation sequencing genome-wide approaches, we identified that BMAL1 binds the promoters of CCNA1 and CDK1 genes and controls their expression in ECs.

Conclusion(s)

Our findings show that EC display a robust circadian clock and that BMAL1 regulates EC physiology in both developmental and pathological contexts. Genetic alteration of BMAL1 can affect angiogenesis in vivo and in vitro settings.
CHARGE syndrome-associated CHD7 acts at ISL1-regulated enhancers to modulate second heart field gene expression
Authors: Stathopoulou Athanasia , Wang Ping , Thellier Charlotte , Kelly Robert G , Zheng Deyou , Scambler Peter J
Published: April 2023

Aims

Haploinsufficiency of the chromo-domain protein CHD7 underlies most cases of CHARGE syndrome, a multisystem birth defect including congenital heart malformation. Context specific roles for CHD7 in various stem, progenitor, and differentiated cell lineages have been reported. Previously, we showed severe defects when Chd7 is absent from cardiopharyngeal mesoderm (CPM). Here, we investigate altered gene expression in the CPM and identify specific CHD7-bound target genes with known roles in the morphogenesis of affected structures.

Methods and results

We generated conditional KO of Chd7 in CPM and analysed cardiac progenitor cells using transcriptomic and epigenomic analyses, in vivo expression analysis, and bioinformatic comparisons with existing datasets. We show CHD7 is required for correct expression of several genes established as major players in cardiac development, especially within the second heart field (SHF). We identified CHD7 binding sites in cardiac progenitor cells and found strong association with histone marks suggestive of dynamically regulated enhancers during the mesodermal to cardiac progenitor transition of mESC differentiation. Moreover, CHD7 shares a subset of its target sites with ISL1, a pioneer transcription factor in the cardiogenic gene regulatory network, including one enhancer modulating Fgf10 expression in SHF progenitor cells vs. differentiating cardiomyocytes.

Conclusion

We show that CHD7 interacts with ISL1, binds ISL1-regulated cardiac enhancers, and modulates gene expression across the mesodermal heart fields during cardiac morphogenesis.
Of Rights and Riots: Indenture and (Mis)Rule in the Late Nineteenth-Century British Caribbean
Authors: Auerbach Sascha
Published: April 2023

This article builds on the work of Walter Rodney, Thomas Holt, Gad Heuman, Diana Paton, and others who have investigated the complexities of post-slavery societies in the Caribbean. It addresses the dynamics of resistance and the re-working of legal and cultural processes that took place in the half-century following emancipation. Whereas indenture plays a tertiary role in these previous analyses, it is the central concern of this article. Through a close examination of the 1872 killing of five indentured Indian workers on the Devonshire Castle plantation, I analyse how the institution of indenture restructured the interrelation of the colonial state, labour control and violence in British Guiana. I consider the killings not only in the context typically employed by Caribbean historians to examine race, labour and violence—that of slave rebellions and African-Caribbean revolts in the post-emancipation era—but also in relation to the 1857 Indian Rebellion and in the context of an Empire-wide narrative that justified violent state repression against colonised peoples. Although this is largely a microhistorical account, I hope to provide some useful avenues of analysis by which indenture (primarily approached until now through the lens of social history) can be more broadly engaged as an institution that catalysed a new relationship between the state and labour management, that fostered new (or, at least, revised) discourses of the role of violence in colonialism, and that generated new patterns of response and resistance among subalterns.
Importance of cystatin C in estimating glomerular filtration rate: the PARADIGM-HF trial
Authors: Tolomeo Paolo , Butt Jawad H , Kondo Toru , Campo Gianluca , Desai Akshay S , Jhund Pardeep S , Køber Lars , Lefkowitz Martin P , Rouleau Jean L , Solomon Scott D , Swedberg Karl , Vaduganathan Muthiah , Zile Michael R , Packer Milton , McMurray John J V
Published: April 2023

Aims

The 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation combining creatinine and cystatin C provides a better estimation of glomerular filtration rate (GFR) compared to the creatinine-only equation.

Methods and results

CKD-EPI creatinine-cystatin C equation (creatinine-cystatin) was compared to creatinine-only (creatinine) equation in a subpopulation of Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM-HF). Patients were categorized according to difference in eGFR using the two equations: Group 1 (<−10 mL/min/1.73 m2, i.e. creatinine-cystatin more than 10 mL/min lower than creatinine), Group 2 (>−10 and <10 mL/min/1.73 m2), and Group 3 (>10 mL/min/1.73 m2, i.e. creatinine-cystatin more than 10 mL/min higher than creatinine). Cystatin C and creatinine were available in 1966 patients at randomization. Median (interquartile range) eGFR difference was −0.7 (−6.4–4.8) mL/min/1.73 m2. Compared to creatinine, creatinine-cystatin led to a substantial reclassification of chronic kidney disease stages. Overall, 212 (11%) and 355 (18%) patients were reallocated to a better and worse eGFR category, respectively. Compared to patients in Group 2, those in Group 1 (lower eGFR with creatinine-cystatin) had higher mortality and those in Group 3 (higher eGFR with creatinine-cystatin) had lower mortality. Increasing difference in eGFR (due to lower eGFR with creatinine-cystatin compared to creatinine) was associated with increasing elevation of biomarkers (including N-terminal pro-B-type natriuretic peptide and troponin) and worsening Kansas City Cardiomyopathy Questionnaire clinical summary score. The reason why the equations diverged with increasing severity of heart failure was that creatinine did not rise as steeply as cystatin C.

Conclusion

The CKD-EPI creatinine-only equation may overestimate GFR in sicker patients.

Clinical Trial Registration

URL: https://www.clinicaltrials.gov; Unique Identifier: NCT01035255.
Multi-centre, prospective randomized comparison of three different substrate ablation strategies for persistent atrial fibrillation
Authors: Li Kaige , Xu Changhao , Zhu Xiyao , Wang Xinhua , Ye Ping , Jiang Weifeng , Wu Shaohui , Xu Kai , Li Xiangting , Wang Ying , Zheng Qidong , Wang Yanzhe , Leng Lihua , Zhang Zengtang , Han Bing , Zhang Yu , Qin Mu , Liu Xu
Published: April 2023

Aims

The optimal strategy for persistent atrial fibrillation (PerAF) is poorly defined. We conducted a multicentre, randomized, prospective trial to compare the outcomes of different ablation strategies for PerAF.

Methods and results

We enrolled 450 patients and randomly assigned them in a 1:1:1 ratio to undergo pulmonary vein isolation and subsequently undergo the following three different ablation strategies: anatomical guided ablation (ANAT group, n = 150), electrogram guided ablation (EGM group, n = 150), and extensive electro-anatomical guided ablation (EXT group, n = 150). The primary endpoint was freedom from atrial fibrillation (AF) lasting longer than 30 s at 12 months after a single ablation procedure. After 12 months of follow-up, 72% (108) of patients in the EXT group were free from AF recurrence, as compared with the 64% (96) in the EGM group (P = 0.116), and 54% (81) in the ANAT group (P = 0.002). The EXT group showed less AF/atrial tachycardia recurrence than the EGM group (60% vs. 50%, P = 0.064) and the ANAT group (60% vs. 37.3%, P < 0.001). The EXT group showed the highest rate of AF termination (66.7%), followed by 56.7% in the EGM group, and 20.7% in the ANAT group. The AF termination signified less AF recurrence at 12 months compared to patients without AF termination (30.1% vs. 42.7%, P = 0.008). Safety endpoints did not differ significantly between the three groups (P = 0.924).

Conclusions

Electro-anatomical guided ablation achieved the most favourable outcomes among the three ablation strategies. The AF termination is a reliable ablation endpoint.
Use and perceived effectiveness of non-pharmacological home remedies for digestive symptoms: a questionnaire-based survey among primary care patients
Authors: Sebo Paul , Gaboreau Yoann , Morel Marie , Haller Dagmar M , Maisonneuve Hubert
Published: April 2023

Background

Patients frequently visit their primary care physician (PCP) for digestive symptoms. We aimed to compile a list of non-pharmacological home remedies (NPHRs) that patients frequently use and find effective so that PCPs can then propose them to their patients with various digestive symptoms.

Methods

In this questionnaire-based survey on the use and perceived effectiveness of NPHRs for digestive symptoms, 50 randomly selected Swiss or French PCPs consecutively recruited 20–25 patients between March 2020 and July 2021. These patients were given a list of 53 NPHRs previously developed by our research team. They were asked whether they used them (Y/N) and whether they considered them to be ineffective, not very effective, moderately effective, or very effective in treating abdominal pain (14 NPHRs), bloating (2), constipation (5), diarrhoea (10), digestion trouble (12), nausea/vomiting (2) and stomach pain (8). We considered NPHRs to be perceived as effective if patients reported that they were moderately or very effective.

Results

A total of 1,012 patients agreed to participate in the study (participation rate = 84.5%, median age = 52 years, women = 61%). The two most frequently used NPHRs were rice cooking water for diarrhoea (29% of patients) and prunes for constipation (22%). The perceived effectiveness of the NPHRs ranged from 82% (fennel infusions for abdominal pain) to 95% (bicarbonate for stomach pain).

Conclusion

Our data could be useful to PCPs interested in proposing NPHRs to their patients suffering from digestive disorders, and more generally to all PCPs interested in learning more about patients’ use of NPHRs in primary care.
Status Seeking through Peacekeeping: Ukraine's Quest for a Positive Social Identity in the International System
Authors: Dobrescu Madalina
Published: April 2023

When do states pursue status enhancement through peacekeeping and how do they go about it? This article argues that states’ contributions to peace operations can be related to attempts at acquiring a positive identity in the international arena through membership in highly ranked groups. Drawing on insights from social identity theory and peacekeeping and burden-sharing research, the article elaborates on how states choose an identity management strategy that involves peacekeeping practices, the factors influencing states’ ability to pursue status through peacekeeping, and the conditions for succeeding in acquiring the desired social identity. Ukraine's significant peacekeeping engagement in the first two decades following independence represents an intriguing case of an emerging state positioning itself in the international and regional systems, which makes it a relevant case study to explore. Therefore, the article discusses how two of Ukraine's formative peacekeeping experiences have fostered, or alternatively undermined, the pursuit of a positive social identity, first as a sovereign state and member of the broader international community and second as an aspiring member of the Western community of states.
A DEAD-box RNA helicase mediates meiotic silencing by unpaired DNA
Authors: Sy Victor T , Boone Erin C , Xiao Hua , Vierling Michael M , Schmitz Shannon F , Ung Quiny , Trawick Sterling S , Hammond Thomas M , Shiu Patrick K T
Published: April 2023

During the sexual phase of Neurospora crassa, unpaired genes are subject to a silencing mechanism known as meiotic silencing by unpaired DNA (MSUD). MSUD targets the transcripts of an unpaired gene and utilizes typical RNA interference factors for its process. Using a reverse genetic screen, we have identified a meiotic silencing gene called sad-9, which encodes a DEAD-box RNA helicase. While not essential for vegetative growth, SAD-9 plays a crucial role in both sexual development and MSUD. Our results suggest that SAD-9, with the help of the SAD-2 scaffold protein, recruits the SMS-2 Argonaute to the perinuclear region, the center of MSUD activity.
Dispersal inference from population genetic variation using a convolutional neural network
Authors: Smith Chris C R , Tittes Silas , Ralph Peter L , Kern Andrew D
Published: April 2023

The geographic nature of biological dispersal shapes patterns of genetic variation over landscapes, making it possible to infer properties of dispersal from genetic variation data. Here, we present an inference tool that uses geographically distributed genotype data in combination with a convolutional neural network to estimate a critical population parameter: the mean per-generation dispersal distance. Using extensive simulation, we show that our deep learning approach is competitive with or outperforms state-of-the-art methods, particularly at small sample sizes. In addition, we evaluate varying nuisance parameters during training—including population density, demographic history, habitat size, and sampling area—and show that this strategy is effective for estimating dispersal distance when other model parameters are unknown. Whereas competing methods depend on information about local population density or accurate inference of identity-by-descent tracts, our method uses only single-nucleotide-polymorphism data and the spatial scale of sampling as input. Strikingly, and unlike other methods, our method does not use the geographic coordinates of the genotyped individuals. These features make our method, which we call “disperseNN,” a potentially valuable new tool for estimating dispersal distance in nonmodel systems with whole genome data or reduced representation data. We apply disperseNN to 12 different species with publicly available data, yielding reasonable estimates for most species. Importantly, our method estimated consistently larger dispersal distances than mark-recapture calculations in the same species, which may be due to the limited geographic sampling area covered by some mark-recapture studies. Thus genetic tools like ours complement direct methods for improving our understanding of dispersal.
BABA-induced pathogen resistance: a multi-omics analysis of the tomato response reveals a hyper-receptive status involving ethylene
Authors: Zapletalová Martina , Rancurel Corinne , Industri Benoit , Bardin Marc , Le Brigand Kevin , Nicot Philippe , Magnone Virginie , Seassau Aurélie , Barbry Pascal , Potěšil David , Zdráhal Zbyněk , Ponchet Michel , Lochman Jan
Published: April 2023

Prior exposure to microbial-associated molecular patterns or specific chemical compounds can promote plants into a primed state with stronger defence responses. β-aminobutyric acid (BABA) is an endogenous stress metabolite that induces resistance protecting various plants towards diverse stresses. In this study, by integrating BABA-induced changes in selected metabolites with transcriptome and proteome data, we generated a global map of the molecular processes operating in BABA-induced resistance (BABA-IR) in tomato. BABA significantly restricts the growth of the pathogens Oidium neolycopersici and Phytophthora parasitica but not Botrytis cinerea. A cluster analysis of the upregulated processes showed that BABA acts mainly as a stress factor in tomato. The main factor distinguishing BABA-IR from other stress conditions was the extensive induction of signaling and perception machinery playing a key role in effective resistance against pathogens. Interestingly, the signalling processes and immune response activated during BABA-IR in tomato differed from those in Arabidopsis with substantial enrichment of genes associated with jasmonic acid (JA) and ethylene (ET) signalling and no change in Asp levels. Our results revealed key differences between the effect of BABA on tomato and other model plants studied until now. Surprisingly, salicylic acid (SA) is not involved in BABA downstream signalization whereas ET and JA play a crucial role.
Stabilization and destabilization of hybrid systems by periodic stochastic controls based on Lévy noise
Authors: Li Wenrui , Fei Weiyin , Liang Yong , Mao Xuerong
Published: April 2023

We focus in this paper on determining whether or not a periodic stochastic feedback control based on Lévy noise can stabilize or destabilize a given non-linear hybrid system. Using the Lyapunov functions and the periodic functions, we establish some sufficient conditions on the stability and instability for non-linear hybrid systems with Lévy noise. Moreover, we use some numerical examples and simulations to illustrate that an unstable (or stable) non-linear hybrid system can be stabilized (or destabilized) via periodic stochastic feedback control based on Lévy noise.
Understanding German Foreign Policy in the (Post-)Merkel Era—Review Essay
Authors: Eberle Jakub
Published: April 2023

This essay reviews four recent books on Germany's foreign policy with emphasis on the era of Angela Merkel. The evaluation is based on their (a) added value to scholarship on German foreign policy, (b) theoretical sophistication and contribution to IR, and (c) relevance also for the post-Merkel era. I argue that the books bring in valuable insights regarding the enduring, yet also changeable role of anti-militarism and provide knowledgeable analyses of the failure of Germany's policies toward Russia. Importantly, they enrich also broader literatures, especially in their focus on discursive change and state power in the European Union context. I demonstrate that these ideas help us understand Germany's struggle to redefine its role after Russia's invasion of Ukraine, and offer more nuanced analyses of Germany's policies and their specifics, staying clear of treating the country as a priori exceptional.
Evaluation of the tolerance of ceftriaxone by subcutaneous route in patients ≥75 years old in geriatric departments: a prospective observational study
Authors: Renoncourt Thomas , Dossoubadjiokila Justine , Mondet Lisa , Pecquet Pauline-Eva , Bennouna Nysrine , Gras-Champel Valerie , Bennis Youssef , Bloch Frédéric
Published: April 2023

Objectives

The subcutaneous (SC) route provides an alternative to the IV or oral route for drug administration in the elderly. The benefits of SC administration have been proven for hydration but are still debated for antibiotics because tolerance remains uncertain, especially in the frail geriatric population. Here, we aimed to improve current knowledge concerning the tolerance profile of ceftriaxone SC administration at both the systemic and cutaneous level, as well as in terms of pain.

Patients and methods

This was a prospective descriptive study of SC ceftriaxone tolerance in a geriatric department. We included all patients over 75 years of age who received a prescription for SC ceftriaxone in our hospital over a 5 month period.

Methods

We evaluated the systemic and local tolerance of SC ceftriaxone. Nurses were asked about their perceptions concerning its use.

Results

Among 117 patients, 57% presented with pain and 60% with a mild local adverse effect, such as the formation of oedema in one-third of patients, induration or transient erythema. Finally, there were no serious local adverse effects and two systemic adverse effects were observed (one diarrhoea and one Clostridioides difficile colitis). Pain was mainly related to the skin breach and oedema formation.

Conclusions

We did not find any worrying signs concerning the use of SC ceftriaxone but this study shows that its wide use must consider pain management, which is often overlooked.
Assessing the Immunization Information System and electronic health record interface accuracy for COVID-19 vaccinations
Authors: McGreevy Sheila , Murray Megan , Montero Leny , Gibson Cheryl , Comfort Branden , Barry Michael , Kirmer-Voss Kalee , Coy Allison , Zufer Tahira , Rampon Kathryn H , Woodward Jennifer
Published: April 2023

Objective

Our objective is to assess the accuracy of the COVID-19 vaccination status within the electronic health record (EHR) for a panel of patients in a primary care practice when manual queries of the state immunization databases are required to access outside immunization records.

Materials and Methods

This study evaluated COVID-19 vaccination status of adult primary care patients within a university-based health system EHR by manually querying the Kansas and Missouri Immunization Information Systems.

Results

A manual query of the local Immunization Information Systems for 4114 adult patients with “unknown” vaccination status showed 44% of the patients were previously vaccinated. Attempts to assess the comprehensiveness of the Immunization Information Systems were hampered by incomplete documentation in the chart and poor response to patient outreach.

Conclusions

When the interface between the patient chart and the local Immunization Information System depends on a manual query for the transfer of data, the COVID-19 vaccination status for a panel of patients is often inaccurate.