bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conclusion: ‘A Covert Form ofWitchcraft’
Authors: Eidinow Esther 
Published: April 2023

AbstractThis chapter returns to the trials of Theoris, Phryne, and Ninon. Drawing together the arguments of the book so far, it suggests that their trials were prompted by social dynamics, and highlights phthonos and gossip. Aeschines’ comments about the trial of Socrates, in which he examines the informal reasons why Socrates was condemned to death, illustrate the important role played by specific social dynamics. The chapter ends by asking what is it that creates the right environment for gossip to become transformed into official legal action.
Hemostatic Net in Facelift Surgery: A 5-Year Single-Surgeon Experience
Authors: Janssen Tim J , Maheshwari Kavish , Sivadasan Anand , Waterhouse Norman 
Published: April 2023

Abstract

Background
The hemostatic net has been promoted as a safe and effective method to prevent hematoma formation following facelift procedures. To date there is little published evidence to validate the replicability and effectiveness of the technique.

Objectives
This study presents 2 cohorts of facelift patients from a single surgeon's practice to assess the impact of the hemostatic net on hematoma formation.

Methods
The records of 304 patients were reviewed on whom the hemostatic net was placed following a facelift between July 2017 and October 2022. Data were collected and assessed for complications and compared with a control group of 359 patients who underwent a facelift procedure without placement of a hemostatic net by the same surgeon between 1999 and 2004.

Results
A total of 663 patients were included. In this retrospective cohort study, analysis of available data showed a significantly reduced hematoma rate of 0.6% in the intervention group compared with 3.9% in the control group (P = .006722).

Conclusions
The use of the hemostatic net is a safe, reproducible, and effective technique in reducing the risk of hematoma in facelift surgery.

Level of Evidence: 4
FISHFactor: a probabilistic factor model for spatial transcriptomics data with subcellular resolution
Authors: Walter Florin C , Stegle Oliver , Velten Britta 
Published: April 2023

AbstractMotivationFactor analysis is a widely used tool for unsupervised dimensionality reduction of high-throughput datasets in molecular biology, with recently proposed extensions designed specifically for spatial transcriptomics data. However, these methods expect (count) matrices as data input and are therefore not directly applicable to single molecule resolution data, which are in the form of coordinate lists annotated with genes and provide insight into subcellular spatial expression patterns. To address this, we here propose FISHFactor, a probabilistic factor model that combines the benefits of spatial, non-negative factor analysis with a Poisson point process likelihood to explicitly model and account for the nature of single molecule resolution data. In addition, FISHFactor shares information across a potentially large number of cells in a common weight matrix, allowing consistent interpretation of factors across cells and yielding improved latent variable estimates.ResultsWe compare FISHFactor to existing methods that rely on aggregating information through spatial binning and cannot combine information from multiple cells and show that our method leads to more accurate results on simulated data. We show that our method is scalable and can be readily applied to large datasets. Finally, we demonstrate on a real dataset that FISHFactor is able to identify major subcellular expression patterns and spatial gene clusters in a data-driven manner.Availability and implementationThe model implementation, data simulation and experiment scripts are available under https://www.github.com/bioFAM/FISHFactor.
A Sensitive Ultra­performance Liquid Chromatography–Tandem Mass Spectrometric Method for Determination of Secalonic Acid F in Rat Plasma and Its Application to Pharmacokinetic Study
Authors: Ji Lei , Wang Pengyue , Wan Qingyun , Wang Gege , Liu Weizhong , Liu Desheng 
Published: April 2023

Abstract
Secalonic acid F (SAF) is a fungal secondary metabolite exhibited interesting pharmacological effect. In this study, a simple and sensitive ultra-performance liquid chromatography–tandem mass spectrometric (UPLC–MS/MS) method was developed and validated for the determination of SAF in rat plasma. Emodin was selected as the internal standard (IS), and plasma samples were prepared by liquid–liquid extraction with ethyl acetate. Chromatographic separation was operated on an Agilent SB-C18 column, and the mobile phase was a mixture of 0.5% formic acid in water and methanol (V:V = 20:80) at a flow rate of 0.3 mL/min. Detection was carried out with a 6460 triple-quadrupole mass spectrometer using electrospray ionization in the multiple-reaction monitoring mode. The MS/MS ion transitions monitored were m/z 639.3 → 415.4 and 269.0 → 225.1 for SAF and IS, respectively. Results showed the calibration curve of SAF was linear in the range of 2–500 ng·mL−1 with the correlation coefficient &gt; 0.99. The matrix effect, extraction recovery, dilution effect, intraday and inter-day precision and accuracy were all in acceptable limits. The analytes were also stable under different conditions. The validated method was successfully applied to a pharmacokinetic study after oral administration in Sprague-Dawley rats at a dose of 10 mg/kg.
Anti-CD20 should be the first-line treatment in high-risk membranous nephropathy
Authors: Zand Ladan , Fervenza Fernando C 
Published: April 2023

ABSTRACT
Membranous nephropathy (MN) is a common cause of nephrotic syndrome (NS) in adults and if untreated can progress to endstage kidney disease. Factors considered to place a patient at high or very high risk for progression include elevated serum creatinine at baseline, declining kidney function, persistent heavy proteinuria (&gt;8 g/24 h), or persistent NS, presence of life-threatening complications related to NS (such as venous thromboembolic events), or very high anti-PLA2R antibody titers (&gt;150 RU/ml). Patients who are at high or very high risk of progression should be treated with immunosuppression therapy to induce remission of proteinuria and to avoid progressive loss of kidney function. Traditional forms of immunosuppression for patients with MN have included the use of cyclic courses of corticosteroids with cyclophosphamide or calcineurin inhibitors. These forms of therapy are associated with significant toxicity, e.g. corticosteroids (infections, diabetes, weight gain), cyclophosphamide (infertility, severe leukopenia, malignancy), and calcineurin inhibitors (hypertension, nephrotoxicity). The introduction of anti-CD20+ B-cell therapies in the late 1990s has changed the landscape. In this article we will argue that anti-CD20+ B therapy should be the treatment of choice for patients at high/very high risk of progression when considering its efficacy and side-effect profile.
Effect of roxadustat on red blood cell lifespan in patients with long-term haemodialysis: a single-centre, prospective, single-arm study
Authors: Zhao Bing , Yang Xiaowei , Li Weidan , Zhu Huizi , Meng Qian , Ma Yongjian , Liu Yun , Zhou Yan , Lin Jiangong , Zhai Chunjuan , Zhao Lian , Sun Jing , Wang Rong 
Published: April 2023

ABSTRACT

Background
Reduced survival of red blood cells (RBCs) in patients with chronic kidney disease (CKD) is thought to contribute to renal anaemia. Although renal anaemia improved greatly because of the wide use of erythropoiesis-stimulating agents (ESAs) and the advancement of dialysis techniques, RBC longevity seems not to be obviously ameliorated.

Methods
In this single-centre, single-arm trial, patients who had been undergoing haemodialysis and ESA therapy with epoetin alfa for at least 12 weeks changed their anti-anaemia drugs from epoetin alfa to oral roxadustat three times per week for 24 weeks. The primary endpoint was the change in RBC lifespan from baseline at week 24. The change in the circulating percentage of eryptotic RBCs, RBC deformability and RBC oxygen transport ability were also assessed.

Results
A total of 27 patients were enrolled, with 26 completing the full course of intervention. At baseline, the average RBC lifespan was 60.1 days [standard deviation (SD) 14.4; n = 27]. At the end of the study period, 26 patients had an RBC lifespan measurement (83.9 days on average; SD 21.9). The RBC lifespan increased by 22.8 days on average [95% confidence interval (CI) 15.5–30.0, P &lt; .001]. This equated to an average RBC lifespan increase of 39.2% (95% CI 27.8–50.6). The percentage of circulating eryptotic RBCs, erythrocyte filtration index and the pressure at which haemoglobin is 50% saturated decreased significantly from baseline to week 24 (1.39 ± 0.44% versus 0.89 ± 0.25%, P &lt; .0001; 0.29 ± 0.12 versus 0.16 ± 0.08, P &lt; .0001 and 32.54 ± 4.83 versus 28.40 ± 2.29, P &lt; .001, respectively).

Conclusion
Roxadustat prolonged RBC lifespan in patients with long-term haemodialysis.
Impact of radiotherapy on adverse events of self-expanding metallic stents in patients with esophageal cancer
Authors: Machado Andressa A , Martins Bruno C , Josino Iatagan R , Chen André T C , Hong Carlos B C , Santos Alisson L D R , Lima Gustavo R A , Cordero Martin A C , Safatle-Ribeiro Adriana V , Pennacchi Caterina , Gusmon Carla C , Paulo Gustavo A , Lenz Luciano , Lima Marcelo S , Baba Elisa R , Kawaguti Fábio S , Uemura Ricardo S , Sallum Rubens A A , Ribeiro Jr Ulysses , Maluf-Filho Fauze 
Published: April 2023

Abstract
Self-expanding metallic stents (SEMS) are considered the treatment of choice for the palliation of dysphagia and fistulas in inoperable esophageal neoplasms. However, the safety of SEMSs in patients who received or who will be submitted to radiotherapy (RT) is uncertain. The study aimed to evaluate the impact of RT on adverse events (AEs) in patients with esophageal cancer with SEMSs. This is a retrospective study conducted at a tertiary cancer hospital from 2009 to 2018. We collected information regarding RT, the histological type of the tumor, the model of SEMSs and AEs after stent placement. Three hundred twenty-three patients with malignant stenosis or fistula were treated with SEMSs. The predominant histological type was squamous cell carcinoma (79.6%). A total of 282 partially covered and 41 fully covered SEMSs were inserted. Of the 323 patients, 182 did not received RT, 118 received RT before SEMS placement and 23 after. Comparing the group that received RT before stent insertion with the group that did not, the first one presented a higher frequency of severe pain (9/118 7.6% vs. 3/182 1.6%; P = 0.02). The group treated with RT after stent placement had a higher risk of global AEs (13/23 56.5% vs. 63/182 34.6%; P = 0.019), ingrowth/overgrowth (6/23 26.1% vs. 21/182 11.5%; P = 0.045) and gastroesophageal reflux (2/23 8.7% vs. 2/182 1.1%; P = 0.034). Treatment with RT before stent placement in patients with inoperable esophageal neoplasm prolongs survival and is associated with an increased risk of severe chest pain. Treatment with RT of patients with an esophageal stent increases the frequency of minor, not life-threatening AEs.
Ability to remotely monitor atrial high-rate episodes using a single-chamber implantable cardioverter-defibrillator with a floating atrial sensing dipole
Authors: Hindricks Gerhard , Theuns Dominic A , Bar-Lev David , Anguera Ignasi , Ayala Paredes Félix Alejandro , Arnold Martin , Geller J Christoph , Merkely Béla , Dyrda Katia Marjolaine , Perings Christian , Maglia Giampiero , Ploux Sylvain , Meyhöfer Jürgen , Blomström-Lundqvist Carina , Karjalainen Pasi , Liang Yanchun , Diemberger Igor , Wranicz Jerzy Krzysztof , Barr Craig , Quartieri Fabio , Timmel Tobias , Bollmann Andreas 
Published: April 2023

Abstract

Aims
To allow timely initiation of anticoagulation therapy for the prevention of stroke, the European guidelines on atrial fibrillation (AF) recommend remote monitoring (RM) of device-detected atrial high-rate episodes (AHREs) and progression of arrhythmia duration along pre-specified strata (6 min…&lt;1 h, 1 h…&lt;24 h, ≥ 24 h). We used the MATRIX registry data to assess the capability of a single-lead implantable cardioverter-defibrillator (ICD) with atrial sensing dipole (DX ICD system) to follow this recommendation in patients with standard indication for single-chamber ICD.

Methods and results
In 1841 DX ICD patients with daily automatic RM transmissions, electrograms of first device-detected AHREs per patient in each duration stratum were adjudicated, and the corresponding positive predictive values (PPVs) for the detections to be true atrial arrhythmia were calculated. Moreover, the incidence and progression of new-onset AF was assessed in 1451 patients with no AF history. A total of 610 AHREs ≥6 min were adjudicated. The PPV was 95.1% (271 of 285) for episodes 6min…&lt;1 h, 99.6% (253/254) for episodes 1 h…&lt;24 h, 100% (71/71) for episodes ≥24 h, or 97.5% for all episodes (595/610). The incidence of new-onset AF was 8.2% (119/1451), and in 31.1% of them (37/119), new-onset AF progressed to a higher duration stratum. Nearly 80% of new-onset AF patients had high CHA2DS2-VASc stroke risk, and 70% were not on anticoagulation therapy. Age was the only significant predictor of new-onset AF.

Conclusion
A 99.7% detection accuracy for AHRE ≥1 h in patients with DX ICD systems in combination with daily RM allows a reliable guideline-recommended screening for subclinical AF and monitoring of AF-duration progression.
Risk-Averse Importance Sampling of Tree Attributes in High-Risk Forested Areas
Authors: Roesch Francis A , Schroeder Todd A , McCollum Joseph M 
Published: April 2023

Abstract
This study develops the theory of risk-averse importance sampling and explains its potential application to forest inventory estimation through the use of a heuristic simulation. When the risk-producing elements of the landscape are known, a risk-averse sampling strategy can be created that results in fewer samples in high-risk areas. Our simulation shows that for certain high-risk populations, risk-averse importance sampling can be highly effective at reducing both risk to field crew members (requiring only 10% of the plot visits in the riskiest category) and sample variance relative to simple random sampling. The method is shown to be especially helpful when a population of values of interest decreases with increasing risk, with a reduction in mean square error (MSE) of 84% to 99% in these cases. The simulation also showed the opposite effect on MSE can be expected when values of interest increase with increasing risk. By increasing field crew safety, risk-averse importance sampling should also improve the frequency and accuracy of field observations, potentially leading to even bigger gains in estimate precision. We recommend risk-averse importance sampling any time hazardous conditions can result in a high number of missing observations and reasonably accurate characterizations of landscape risks can be developed.
Identification of immune cell infiltration landscape for predicting prognosis of colorectal cancer
Authors: Wu Xueqian , Li Jianxia , Zhang Yuanzhe , Cheng Yi , Wu Zehua , Zhan Weixiang , Deng Yanhong 
Published: April 2023

AbstractBackgroundThe tumor microenvironment plays an essential role in the therapeutic response to immunotherapy. It is necessary to identify immune cell infiltration (ICI) subtypes for evaluating prognosis and therapeutic benefits. This study aimed to evaluate the ICI score as an effective prognostic biomarker for immune response.MethodsThe cell-type identification by estimating relative subsets of RNA transcripts and the estimation of stromal and immune cells in malignant tumors using expression methods were used to analyse ICI landscapes in 161 colorectal cancer (CRC) samples with patients’ clinical and prognostic data, RNA sequencing data, and whole-exome sequencing data from the Sixth Affiliated Hospital, Sun Yat-sen University (Guangzhou, China). Statistical analysis and data processing were conducted to calculate ICI scores, and to analyse the prognosis of CRC patients with different ICI scores and other features. A similar analysis with RNA sequencing and clinical data of colon adenocarcinoma (COAD) samples from The Cancer Genome Atlas (TCGA) database was conducted to confirm the correctness of the findings.ResultsThe high-ICI score group with a better prognosis (hazard ratio [HR], 2.19; 95% confidence interval [CI], 1.03–4.64; log-rank test, P = 0.036) was characterized by the increased tumor mutational burden and interleukin-17 (IL-17) signaling pathway. Significant differences in the prognosis and the expression levels of immune checkpoints and chemokine marker genes were found between the two ICI score groups. For COAD samples from TCGA, the results also showed a significant difference in patients’ prognosis between the two ICI score groups (HR, 1.72; 95% CI, 1.00–2.96; log-rank test, P = 0.047).ConclusionsTumor heterogeneity induced differences in identifying ICI subtypes of CRC patients. The ICI score may serve as an effective biomarker for predicting prognosis, help identify new therapeutic markers for CRC, and develop novel effective immune checkpoint blockade therapies.
Siegel Zeros, Twin Primes, Goldbach’s Conjecture, and Primes in Short Intervals
Authors: Matomäki Kaisa , Merikoski Jori 
Published: April 2023

Abstract
We study the distribution of prime numbers under the unlikely assumption that Siegel zeros exist. In particular, we prove for $$ \begin{align*} & \sum_{n \leq X} \Lambda(n) \Lambda(\pm n+h) \end{align*}$$an asymptotic formula that holds uniformly for $h = O(X)$. Such an asymptotic formula has been previously obtained only for fixed $h$ in which case our result quantitatively improves those of Heath-Brown (1983) and Tao and Teräväinen (2021). Since our main theorems work also for large $h$, we can derive new results concerning connections between Siegel zeros and the Goldbach conjecture and between Siegel zeros and primes in almost all very short intervals.
Impact of long-term care insurance on health inequality in older adults in China based on the concentration index approach
Authors: Tian Yong , Fan Lijun , Zhou Menghan , Du Wei 
Published: April 2023

Abstract

Background
Several studies have shown that social security would reduce health inequalities. However, little was known about the relationship between long-term care insurance and health inequality. We aimed to evaluate the impact of long-term care insurance on health status and health inequality in older adults using a nationally representative cohort.

Methods
Based on four waves of data from the China Health and Retirement Longitudinal Study (CHARLS 2011, 2013, 2015 and 2018), we used the staggered difference in difference (DID) design with the order probit regression models and the concentration index approach as well as decomposition analysis to assess the contribution of long-term care insurance towards residents’ health status and health inequality in older adults aged ≥65 y. We further used the semi-parametric DID model for robustness testing.

Results
Long-term care insurance demonstrated its role, improving self-assessed health in the study population (βcoefficient: 0.090, 95% CI 0.087 to 0.092, p&lt;0.001). The estimation results of the semi-parametric DID were consistent with those of the staggered DID. The income-related health concentration index was 0.0005, having a contribution rate of 1.639% to health inequality in older adults. Decomposition analysis revealed that different policies and residential areas were more influential on the observed health inequalities.

Conclusions
The findings implied that long-term care insurance has widened the health inequality while improving health status in older adults. Additional investment in more comprehensive insurance coverage and increased accessibility to enhance implementation of long-term care insurance is warranted to close the gap.
Exploring the epidemiology of mcr genes, genetic context and plasmids in Enterobacteriaceae originating from pigs and humans on farms in Thailand
Authors: Leangapichart Thongpan , Stosic Milan S , Hickman Rachel A , Lunha Kamonwan , Jiwakanon Jatesada , Angkititrakul Sunpetch , Magnusson Ulf , Van Boeckel Thomas P , Järhult Josef D , Sunde Marianne 
Published: April 2023

Abstract

Objectives
In veterinary medicine, colistin has been widely used as therapeutic and prophylactic agent, and for growth promotion. However, colistin has been re-introduced into treatment of human MDR bacterial infections. We assessed the characteristics and spread of plasmid-borne colistin resistance among healthy pigs, workers with animal-contact and their household members in Thailand.

Methods
WGS and MIC data of 146 mcr-positive isolates from a cross-sectional One Health study were analysed. Long-read sequencing and conjugation were performed for selected isolates.

Results
mcr-carrying isolates were detected in 38% of pooled-pig samples and 16% of human faecal samples. Of 143 Escherichia coli and three Escherichia fergusonii, mcr-1, mcr-3, and mcr-9 variants were identified in 96 (65.8%), 61 (41.8%) and one (0.7%) isolate, respectively. Twelve E. coli co-harboured two mcr variants (mcr-1 and mcr-3). Clonal transmission was detected in five out of 164 farms. mcr-1 was mostly harboured by epidemic IncX4 and IncHI1 plasmids (89.9%). Conversely, mcr-3 was harboured by a range of different plasmids. Comparative plasmid studies suggested IncP and IncFII plasmids as possible endemic mcr-3 plasmids in Asian countries. Moreover, mcr-3 was associated with different mobile genetic elements including TnAs2, ISKpn40 and IS26/15DI. Detected genetic signatures (DRs) indicated recent mcr-3 transpositions, underlining the mobilizable nature of the mcr-3 cassette.

Conclusions
The epidemiology of mcr and the possible evolution of successful plasmids and transposition modules should be carefully monitored. Of special concern is the growing number of different horizontal gene transferring pathways encompassing various transposable modules the mcr genes can be shared between bacteria.
Using elemental staining and mapping techniques for simultaneous visualization of biological structures in the nucleus by multichannel electron microscopy
Authors: Strickfaden Hilmar , Abate Natnael , Förster Christian , Wuest Frank , Underhill D Alan , Hendzel Michael J 
Published: April 2023

Abstract
Transmission electron microscopy (TEM) has been essential in defining the structural organization of the cell due to its ability to image cell structures at molecular resolution. However, the absence of colour has made it very difficult to compare the distributions and relationships of two or more types of biomolecules simultaneously if they lack clear morphological distinctions. Furthermore, single-channel information limits functional analysis, particularly in the nucleoplasm, where fibrillar material could be chromatin, ribonucleic acid or protein. Where specific stains exist to discriminate among these molecules, they cannot be combined because conventional TEM is a single-channel technology. A potential path around this barrier is through electron spectroscopic imaging (ESI). ESI can map the distributions of chemical elements within an ultrathin section. Here, we present methods to stain specific molecules with elements that ESI can visualize to enable multichannel electron microscopy.