bluuebunny/crossref_metadata_2025 huggingface dataset:
Incomplete activation and ionization of dopants in Si at room temperature
Authors: Abenante Luigi
Published: January 2023

A new model for incomplete ionization of dopants in Si is presented, where the Fermi level of free carriers may displace with respect to the case of full activation of dopants. The curves of the ratio of free-carrier density and active-dopants density vs doping, which are calculated at partial activation of dopants with the new model, overlap exactly with the curves of the same quantity calculated at full activation of dopants with a reported model. Calculations are performed with and without reported parameterizations of the density of states and occupancy probability of the dopant band simulating incomplete ionization around the Mott concentration. With parameterizations, comparisons with Hall-mobility data show that the curves of free-carrier density calculated at partial dopant activation with the new model are more accurate than the curves of the same quantity calculated at full dopant activation with the reported model. Without parameterizations, the new model allows calculating for the same carrier species curves of majority-carrier mobility that fit measured data of minority-carrier mobility at high dopings and agree with the Klaassen mobility model for minority carriers. The consistency with the band theory of the new and reported models is discussed, and the new model is found to be the most appropriate in this respect. The free-carrier density calculated with the new model without parameterizations overlaps at high dopings with free-carrier density calculated with reported models for band-gap narrowing and allows calculating curves of Auger lifetime of majority carriers that fit measured lifetime data of minority carriers.
Strong and ductile medium manganese steel processed by low-temperature partitioning
Authors: Yi Li , Xuekun Shang , Qingwen Guan , Binbin He
Published: January 2023

Conventional medium Mn steels processed by intercritical annealing (IA) demonstrate low yield strength. The present work investigates the effect of low-temperature partitioning (LTP) on the microstructure and tensile properties of medium Mn steel. It is found that medium Mn steel processed by LTP at 300°C possesses ultra-high yield strength of 1683 MPa and proper uniform elongation of 11.3%. The LTP process does not reduce the yield strength but substantially enhances the tensile ductility. The increase of the tensile ductility after LTP treatment can be ascribed to the reduction of the residual stress, martensitic transformation, and the well-developed ductile fracture behaviour. The present LTP process provides an alternative pathway to develop strong and ductile medium Mn steel.
Outer retinal degeneration in a non-human primate model using temporary intravitreal tamponade with N-methyl-N-nitrosourea in cynomolgus monkeys
Authors: Choi Kwang-Eon , Cha Seongkwang , Yun Cheolmin , Ahn Jungryul , Hwang Seil , Kim Young-Jin , Jung Hachul , Eom Heejong , Shin Dongkwan , Oh Jaeryung , Goo Yong Sook , Kim Seong-Woo
Published: January 2023

Objective: The main objective of this study was to induce and evaluate drug-dose-dependent outer retinal degeneration in cynomolgus monkeys by application of N-methyl-N-nitrosourea (MNU). Approach: Intravitreal temporary tamponade induced outer retinal degeneration with MNU solutions (2–3 mg ml−1) after vitrectomy in five cynomolgus monkeys. Optical coherence tomography (OCT), fundus autofluorescence (FAF), full-field electroretinography (ffERG), and visual evoked potentials (VEP) were performed at baseline and weeks 2, 6, and 12 postoperatively. At week 12, OCT angiography, histology, and immunohistochemistry were performed. Main results: Outer retinal degeneration was observed in four monkeys, especially in the peripheral retina. Anatomical and functional changes occurred at week 2 and persisted until week 12. FAF images showed hypoautofluorescence dots, similar to AF patterns seen in human retinitis pigmentosa. Hyperautofluorescent lesions in the pericentral area were also observed, which corresponded to the loss of the ellipsoid zone on OCT images. OCT revealed thinning of the outer retinal layer adding to the loss of the ellipsoid zone outside the vascular arcade. Histological findings confirmed that the abovementioned changes resulted from a gradual loss of photoreceptors from the perifovea to the peripheral retina. In contrast, the inner retina, including ganglion cell layers, was preserved. Functionally, a decrease or extinction of scotopic ffERGs was observed, which indicated rod-dominant loss. Nevertheless, VEPs were relatively preserved. Significance: Therefore, we can conclude that temporary exposure to intravitreal MNU tamponade after vitrectomy induces rod-dominant outer retinal degeneration in cynomolgus monkeys, especially in the peripheral retina.
Nanoprecipitates enhanced wear resistance of laser powder bed fusion-processed high-strength Al−Cu−Mg−Si−Ti alloy
Authors: Wang Qingzheng , El Mansori Mohamed , El hadrouz Mourad , Kang Nan , Lin Xin
Published: January 2023

Solidification cracking during laser powder bed fusion (LPBF) and poor wear resistance of high-strength aluminum alloys hinder their application in aerospace and automotive fields. In the present work, a novel defect-free Al-Cu-Mg-Si-Ti alloy was manufactured by LPBF. The densification behavior research shows that the threshold value to manufacture the full-density Al-Cu-Mg-Si-Ti alloy by LPBF is a volumetric energy density (VED) of 141.7 J mm−3. The LPBF processed sample shows a heterogeneous microstructure consisting of ultrafine equiaxed grains and columnar grains. Dry sliding tests indicate that the wear rate of the as-built samples is 3.9 ± 0.4 × 10−5 cm3 m−1 with dominant abrasive wear under an applied load of 2.1 N. At an applied load of 24 N, the wear mechanism transforms to severe delamination and abrasion with a high wear rate of 42.1 ± 0.1 × 10−5 cm3 m−1. After the aging treatment, the size and number density of nanosized S’ and Q’ precipitated phases increase significantly, which results in an increased hardness and better wear resistance.
A study on hot deformation behavior of Ti-6Al-2V-0.5Zr-1.5Mo alloys
Authors: Ren Ke , Zheng Biju
Published: January 2023

Ti-6Al-2V-0.5Zr-1.5Mo alloys is a new type of titanium alloys developed on the basis of Ti-6Al-4V alloys. Compared with Ti-6Al-4V alloys, they are low in cost and excellent in performance. To offer an idea for hot working production, their thermal deformation behavior was studied through a Gleeble3500 machine, and the microstructure evolution during the thermal deformation was analyzed. After the experiment, the true stress-strain curves at strain rates of 0.001 s−1, 0.01 s−1, 0.1 s−1 and 1 s−1 at temperatures of 800 °C, 850 °C, 900 °C, and 950 °C were worked out. The result showed that the flow stress decreased as the deformation temperature rose and the strain rate fell. The peak stress constitutive equation and flow stress prediction model were built through the Arrhenius equation. The correlation coefficient between the predicted data and the experimental data reached 0.9811, which meant that the flow stress could be predicated accurately through Arrhenius equation. In addition, the processing map was established based on the DMM theory, and the best process parameters of such an alloy were figured out.
Quantum machine learning of large datasets using randomized measurements
Authors: Haug Tobias , Self Chris N , Kim M S
Published: January 2023

Quantum computers promise to enhance machine learning for practical applications. Quantum machine learning for real-world data has to handle extensive amounts of high-dimensional data. However, conventional methods for measuring quantum kernels are impractical for large datasets as they scale with the square of the dataset size. Here, we measure quantum kernels using randomized measurements. The quantum computation time scales linearly with dataset size and quadratic for classical post-processing. While our method scales in general exponentially in qubit number, we gain a substantial speed-up when running on intermediate-sized quantum computers. Further, we efficiently encode high-dimensional data into quantum computers with the number of features scaling linearly with the circuit depth. The encoding is characterized by the quantum Fisher information metric and is related to the radial basis function kernel. Our approach is robust to noise via a cost-free error mitigation scheme. We demonstrate the advantages of our methods for noisy quantum computers by classifying images with the IBM quantum computer. To achieve further speedups we distribute the quantum computational tasks between different quantum computers. Our method enables benchmarking of quantum machine learning algorithms with large datasets on currently available quantum computers.
Indian heatwaves in a future climate with varying hazard thresholds
Authors: Rao K Koteswara , Jyoteeshkumar Reddy P , Chowdary Jasti S
Published: January 2023

India has experienced remarkable changes in temperature extremes in recent decades due to rapid global warming leading to extreme heat events with disastrous societal impacts. In response to continuing global warming, this study investigates summertime (March–June) heatwave characteristics over India in the present and future climate. During 1951–2020, India Meteorological Department observational data show rising trends in heatwave characteristics such as frequency, intensity, duration, and season length, mainly over India’s northwest, central, and south peninsular regions. Further, the present study explores the changes in future heatwave characteristics using the state-of-the-art statistically downscaled bias-corrected climate models data from Coupled Model Intercomparison Project Phase 6 (CMIP6) of the Shared Socioeconomic Pathway scenario. This study uses varying hazard thresholds, namely fixed (time-invariant historical climatological threshold) and decadal moving thresholds (time-varying future climatological threshold), to define heatwaves and examine the future changes in heatwave characteristics over India. Results show a significant increase in mean summertime heatwaves defined using fixed thresholds in terms of their frequency, duration, number, amplitude, cumulative magnitude, and season length in the near future (NF) (2025–2054) and the far future (FF) (2065–2094) compared to the baseline period (1985–2014) over much of India, with the most substantial increases seen in the FF. However, heatwaves defined using the decadal moving thresholds show no significant changes in their characteristics during the NF but a substantial change in the FF over many parts of India. This work is the first attempt to use bias-corrected CMIP6 models data to project heatwave characteristics utilising the concept of the varying hazard thresholds across India. Overall, this study provides a comprehensive assessment of climate change’s impact on Indian heatwaves, which can help in planning better adaptation and mitigation strategies.
GlobeCorr: interactive globe-based visualization for correlation datasets
Authors: Arab Mariam , Woods Nolan , Garlock Emma S , Winsor Geoffrey L , Parks Jaclyn P , Jia Baofeng , Doiron Dany , Takaro Tim K , Brook Jeffrey R , Brinkman Fiona S L
Published: January 2023

Motivation

Increasingly complex omics datasets are being generated, along with associated diverse categories of metadata (environmental, clinical, etc.). Looking at the correlation between these variables can be critical to identify potential confounding factors and novel relationships. To date, some correlation globe software has been developed to aid investigations; however, they lack secure, dynamic visualization capability.

Results

GlobeCorr.ca is a web-based application designed to provide user-friendly, interactive visualization and analysis of correlation datasets. Users load tabular data listing pairwise variables and their correlation values, and GlobeCorr creates a dynamic visualization using ribbons to represent positive and negative correlations, optionally grouped by domain/category (such as microbiome taxa against other metadata). GlobeCorr runs securely (locally on a user’s computer) and provides a simple method for users to visualize and summarize complex datasets. This tool is applicable to a wide range of disciplines and domains of interest, including the bioinformatics/microbiome and metadata examples provided within.

Availability and Implementation

See https://GlobeCorr.ca; Code provided under an open source MIT license: https://github.com/brinkmanlab/globecorr.
Lifestyle trajectories and ischaemic heart diseases: a prospective cohort study in UK Biobank
Authors: Gao Yinyan , Chen Yancong , Hu Mingyue , Song Jinlu , Zhang Zixuan , Sun Hui , Wang Jiali , Lin Yijuan , Wu Irene X Y
Published: January 2023

Aims

To evaluate the associations of baseline and long-term trajectories of lifestyle with incident ischaemic heart diseases (IHDs).

Methods and results

29 164 participants in the UK Biobank who had at least one follow-up assessment and were free of IHD at the last follow-up assessment were included. We constructed a weighted unhealthy lifestyle score though summing five lifestyle factors [smoking, physical activity, diet, body mass index, and sleep duration]. Lifestyle assessed at baseline (2006–09), the first follow-up assessment (2012–13), and the second follow-up assessment (since 2014) were used to derive the trajectories of each individual. The joint categories were created through cross-classifying the three baseline lifestyle categories (ideal, intermediate, and poor) by the three lifestyle trajectory categories (improve, maintain, and decline). During a median follow-up period of 4.2 years, 868 IHD events were recorded. The hazard ratio (HR) of incident IHD associated with per unit increase in unhealthy lifestyle trajectory was 1.08 [95% confidence interval (CI): 0.99–1.17]. Subgroup analyses indicated such association was stronger among individuals with hypertension (HR: 1.13, 95% CI: 1.03–1.24), diabetes (HR: 1.23, 95% CI: 0.96–1.58), or hyperlipidaemia (HR: 1.09, 95% CI: 0.97–1.22). Compared with participants consistently adhering to an ideal lifestyle (ideal–maintain), the HRs of incident IHD were 1.30 (1.07–1.58) for intermediate–maintain, 1.52 (1.23–1.88) for poor–maintain, 1.25 (0.93–1.68) for intermedia–improve, 1.48 (1.17–1.88) for poor–improve, 1.46 (1.08–1.99) for intermedia–decline, and 1.77 (1.21–2.59) for poor–decline.

Conclusions

A declined lifestyle trajectory increased the risk of incident IHD, irrespective of baseline lifestyle levels. Individuals with hypertension, diabetes, or hyperlipidaemia were more predisposed to the influence of lifestyle change.
1. The State of Nature
Authors: Wolff Jonathan
Published: January 2023

This chapter examines whether it is possible for human beings to live in a state of nature. Sometimes it is claimed that not only have human beings always lived under a state, but that it is the only way they possibly could live. On this view, which is often associated with Aristotle, the state exists naturally in the sense of being natural to human beings. In response, some theorists argue that human beings have been able to live without the state. To elucidate the issue further, this chapter analyses the views of Thomas Hobbes, John Locke, and Jean-Jacques Rousseau. It also considers the arguments of anarchists and suggests that the gap between rational anarchism and the defence of the state is vanishingly small.
3. Who Should Rule?
Authors: Wolff Jonathan
Published: January 2023

This chapter considers the question of what sort of state and government we should have. A common assumption is that only a democracy is ever fully justifiable. Anything else—a tyranny, an aristocracy, an absolute monarchy—lacks justification. But what is a democracy? Is it really so attractive? The chapter explores some of the most fundamental problems in formulating democratic theory before looking at arguments for and against democracy itself. It first examines the tension between the idea of democracy as a system of ‘majority rule’, and the idea of democratic ‘consideration for individuals’. It then analyses Plato’s arguments against democracy, focusing on his use of the so-called craft analogy to defend his position, along with his concept of guardianship. It also discusses Jean-Jacques Rousseau’s notion of the general will and concludes with an overview of representative democracy.
4. The Place of Liberty
Authors: Wolff Jonathan
Published: January 2023

This chapter explores the theory that, to avoid the ‘tyranny of the majority’, we should be given the liberty to act just as we wish, provided that we do no harm to others. The focus is on John Stuart Mill’s Liberty Principle (also known as the Harm Principle), according to which you may justifiably limit a person’s freedom of action only if they threaten harm to another. The chapter considers Mill’s arguments based on the Liberty Principle, including his claim there should be complete freedom of thought and discussion, and that harming another’s interests is not a sufficient condition to justify constraint. It also discusses justifications for the Liberty Principle by focusing on issues of rights and utility, individuality and progress, and liberty as an intrinsic good. It concludes with an analysis of some of the problems of the kind of liberalism espoused by Mill’s Liberty Principle.
5. The Distribution of Property
Authors: Wolff Jonathan
Published: January 2023

This chapter examines the concept of distributive justice, asking in particular whether citizens should have the liberty to acquire and dispose of property however they see fit, or whether there are justified restrictions on economic activity in the name of liberty or justice. It begins with a discussion of the problem of distributive justice, taking into account a variety of differing opinions on how a liberal society should distribute property, along with the so-called income parade. It then considers property and markets, focusing on John Locke’s ideas, and the free market principle. It also explores John Rawls’s theory of justice and some of the criticisms levelled against him, including those by Robert Nozick.
6. Justice for Everyone, Everywhere?
Authors: Wolff Jonathan
Published: January 2023

This chapter examines some issues that have come to greater attention in more recent decades, with particular emphasis on what it calls ‘oversights’ of justice. It begins by arguing that some of the greatest political philosophers suffered from ‘oversights’, notably Karl Marx, Mary Wollstonecraft, and John Stuart Mill. It then considers some of these oversights of justice, first by looking at issues of gender equality, then at racial justice, followed by issues of disability and sexual orientation, each from the standpoint of what is known as ‘domestic justice’: justice as it operates within a single state. It also explores questions of global justice, including immigration, and global inequalities of wealth, along with justice to future generations, especially in relation to climate change. These discussions reflect areas of great contemporary concern, both in political philosophy and in real life.
2. Globalization and global politics
Authors: McGrew Anthony
Published: January 2023

This chapter examines the characteristics of contemporary globalization and how they are reshaping world politics. It argues that both the Covid-19 pandemic and climate change are indicative of just how deeply enmeshed the fate of communities and societies across the world has become, not to mention how globalization simultaneously unifies and divides the world. It explains why globalization challenges some of our traditional ways of thinking and theorizing about world politics. It asks whether there are limits to globalization or whether it is inevitable. It also considers the extent to which globalization is responsible for the emerging shift in the structure of world power, namely the ‘decline of the West’ and the ‘rise of the rest’. Two case studies are presented: one is about global food security and the other is about multicentric globalization.
18. Race in world politics
Authors: Shilliam Robbie
Published: January 2023

This chapter examines the ways in which race can been understood as a fundamental ordering principle of world politics. It explores how the histories of European imperialism and colonialism are crucial for understanding the global impact of race, and whether contemporary world politics is less racist than it was in the past. It also considers the relationship between race, biology, and culture. The chapter concludes by discussing the historical processes that gave rise to race, some key debates around the conceptualization of race, and how race continues to order world politics. Two case studies are presented: the first is about race, caste, and Dalits in India; the second looks into the world of ecofascism.
Ethanolic leaf extract ofDatura stramoniumattenuates methotrexate-induced biochemical alterations in Wistar Albino rats
Authors: Alum Esther U , Inya Joseph E , Ugwu Okechukwu P C , Obeagu Emmanuel I , Aloke Chinyere , Aja Patrick M , Okpata Mmesoma G , John Esther C , Orji Manasseh O , Onyema Ozioma
Published: January 2023

Objectives

Methotrexate (MTX) is a commonly used anti-cancer drug. However, its usage could lead to various biochemical dysregulations culminating in organ toxicity. Globally, most plant products have been used for the treatment of several diseases. Thus, we investigated the effect of Datura stramonium ethanolic leaf extract (DSELE) supplementation in MXT-induced biochemical alterations in rats.

Methods

Rats were divided into four groups: Group 1 received normal saline (5 mg/kg b. w), Group 2 received DSELE (200 mg/kg), Group 3 received 20 mg/kg MXT while rats in Group 4 received 200 mg/kg + MTX 20 mg/kg. Normal saline and DSELE were administered per os for 21 days while MXT single injection was given intraperitoneally on day 18 and the rats were sacrificed after 3 days. Thereafter, biochemical parameters were evaluated.

Key findings

MTX caused a significant (P < 0.05) increase in serum activities of liver enzymes (AST, ALT and ALP) and levels of total cholesterol and low-density lipoprotein while the levels of total protein and albumin decreased significantly relative to the normal control. Interestingly, DSELE administration favourably modulated MXT-induced biochemical alterations to levels comparable to normal control.

Conclusions

DSELE can be a useful combinatorial natural product in MTX chemotherapy since it mitigates MXT-induced biochemical alterations in rats.
Secure reconstruction after pancreaticoduodenectomy: Review and improved our continuous duct-to-mucosa anastomosis
Authors: Hwang Tsann-Long , Kao Hao-Wei , Hsu Chih-Po , Hsu Jun-Te , Yeh Chun-Nan , Yeh Ta-Sen
Published: January 2023

Pancreatic anastomotic leakage is the most common major complication after pancreaticoduodenectomy (PD). The incidence of pancreatic anastomotic leak or fistula has declined to less than 20%, and mortality from this complication has decreased to less than 10% in recent years. The ideal surgical procedures to achieve the most secure pancreaticojejunostomy were compared and reviewed. A single-institution and personal experience was retrogradely compared with two periods between 1988 and 2017, which involved 121 patients who were designed to compare the outcome of complications with or without pancreatic stump by four to six sutures before continuous duct-to-mucosa PD. The surgical reconstruction technique was standardized and unique, and the pancreaticojejunal anastomosis was created using the duct-to-mucosa without (group A, n = 62) and with (group B, n = 59) interrupted stump sutures. The rate of grade A pancreatic fistula was 6.9% in group A and 0% in group B (P < 0.05). Postoperative mortality was 0% in group B. No patient underwent reoperative PD due to pancreatic anastomotic leak. The length of stay during admission and after surgery was significant lower in group B, which was due to less complication after surgery. Interrupted suture of pancreatic stump with a continuous duct-to-mucosa end-to-side pancreaticojejunostomy plus external drainage is the best secure method for pancreaticojejunostomy after PD.
The effects of nuclear DNA mutations on mitochondrial function
Authors: Heuer Beth
Published: January 2023

The multiple functions of mitochondria, including adenosine triphosphate synthesis, are controlled by the coordination of both the mitochondrial DNA (mtDNA) and the nuclear DNA (nDNA) genomes. Mitochondrial disorders manifest because of impairment of energy metabolism. This article focuses on mutations in two nuclear genes and their effect on mitochondrial function. Mutations in the polymerase gamma, or POLG, gene are associated with multisystemic disease processes, including Alpers Syndrome, a severe childhood-onset syndrome. Mutations in the OPA1 gene are associated with autosomal dominant optic atrophy and other neurologic, musculoskeletal, and ophthalmologic symptoms. When assessing for disorders affecting energy metabolism, sequencing of both the mtDNA genome and the nDNA whole exome sequencing is necessary.
Changes in von Willebrand Factor Multimers, Concentration, and Function During Pediatric Extracorporeal Membrane Oxygenation*
Authors: Van Den Helm Suelyn , Letunica Natasha , Barton Rebecca , Weaver Asami , Yaw Hui Ping , Karlaftis Vasiliki , McCafferty Conor , Cai Tengyi , Newall Fiona , Horton Stephen B. , Chiletti Roberto , Johansen Amy , Best Derek , McKittrick Joanne , Butt Warwick , d’Udekem Yves , MacLaren Graeme , Linden Matthew D. , Ignjatovic Vera , Monagle Paul
Published: January 2023

OBJECTIVES:

To investigate changes in von Willebrand factor (VWF) concentration, function, and multimers during pediatric extracorporeal membrane oxygenation (ECMO) and determine whether routine monitoring of VWF during ECMO would be useful in predicting bleeding.

DESIGN:

Prospective observational study of pediatric ECMO patients from April 2017 to May 2019.

SETTING:

The PICU in a large, tertiary referral pediatric ECMO center.

PATIENTS:

Twenty-five neonates and children (< 18 yr) supported by venoarterial ECMO.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Arterial blood samples were collected within 24 hours pre-ECMO, daily for the first 5 days of ECMO, every second day until decannulation, and 24 hours post-ECMO. The STA R Max analyzer was used to measure VWF antigen (VWF:Ag) and ristocetin cofactor (VWF:RCo) activity. VWF collagen binding (VWF:CB) was measured using an enzyme-linked immunosorbent assay. VWF multimers were measured using the semi-automated Hydragel 11 VWF Multimer assay. Corresponding clinical data for each patient was also recorded. A total of 25 venoarterial ECMO patients were recruited (median age, 73 d; interquartile range [IQR], 3 d to 1 yr). The median ECMO duration was 4 days (IQR, 3–8 d) and 15 patients had at least one major bleed during ECMO. The percentage of high molecular weight multimers (HMWM) decreased and intermediate molecular weight multimers increased while patients were on ECMO, irrespective of a bleeding status. VWF:Ag increased and the VWF:RCo/VWF:Ag and VWF:CB/VWF:Ag ratios decreased while patients were on ECMO compared with the baseline pre-ECMO samples and healthy children.

CONCLUSIONS:

Neonates and children on ECMO exhibited a loss of HMWM and lower VWF:CB/VWF:Ag and VWF:RCo/VWF:Ag ratios compared with healthy children, irrespective of major bleeding occurring. Therefore, monitoring VWF during ECMO would not be useful in predicting bleeding in these patients and changes to other hemostatic factors should be investigated to further understand bleeding during ECMO.
Diffusion Weighted MRI could precisely predict the pTERT mutation status of GBM using a residual convolutional neural network
Authors: Hu Congman , Fang Ke , Du Quan , Chen Jiarui , Wang Lin , Li Lanjuan , Zhang Jianmin , Bai Ruiliang , Wang Yongjie
Published: January 2023

Background

Telomerase reverse transcriptase promoter (pTERT) mutation status plays a key role in the decision-making and prognosis prediction of glioblastoma (GBM). The purpose of this study was to assess the prediction value of diffusion-weighted imaging (DWI) in the pTERT mutation status of GBM

Methods

MR imaging data and molecular information of 266 patients with GBM were obtained from the Second Affiliated Hospital of Zhejiang University (n=266). We trained the same residual convolutional neural network (ResNet) for each MR modality, including structural MRIs (T1-weighted, T2-weighted, contrast enhanced T1-weighted) and DWI and its associated ADC map, and their combinations to compare the predictive capacities between DWI and conventional structural MRI. Moreover, we explored the effect of different Region of interests (ROIs) on the outcome of pTERT mutation status prediction: entire tumor (solid tumor, edema and cystic regions), tumor core (solid tumor), and enhanced tumor.

Results

Structural MRI modalities and their combination performed poorly in predicting the pTERT mutation status (accuracy, 51-54%, AUC, 0.545-0.571), while DWI in combination with its ADC maps yielded the best predictive performance (accuracy = 85.2%, AUC= 0.934). The further including of radiological and clinical characteristics could not further improve the predictive performance of pTERT mutation status. Among the three ROI selections, the entire tumor volume yielded the best prediction performance.

Conclusion

DWI and its associated ADC maps shows promising prediction value in the pTERT mutation in GBM and are suggested to be included into the MRI protocol of GBM in clinical practice.

Key Points

The ResNet model constructed by radiomics provided great help for the prediction of pTERT mutation in glioblastoma.

In the ResNet prediction model, conventional structural MRI was of little value while DWI and its associated ADC maps shows excellent value.

The model using the whole tumor as ROI showed best predictive capacity and potentiality for future clinical application.
Cancer Cell’s Seven Achilles Heels: Considerations for design of anti-cancer drug combinations
Authors: Gahramanov Valid , Vizeacoumar Frederick S. , Morales Alain Morejon , Bonham Keith , Sakharkar Meena K. , Vizeacoumar Franco J. , Freywald Andrew , Sherman Michael Y.
Published: January 2023

Loss of function screens using shRNA and CRISPR are routinely used to identify genes that modulate responses of tumor cells to anti-cancer drugs. Here, by integrating GSEA and CMAP analyses of multiple published shRNA screens, we identified a core set of pathways that affect responses to multiple drugs with diverse mechanisms of action. This suggests that these pathways represent “weak points” or “Achilles heels”, whose mild disturbance should make cancer cells vulnerable to a variety of treatments. These “weak points” include proteasome, protein synthesis, RNA splicing, RNA synthesis, cell cycle, Akt-mTOR, and tight junction-related pathways. Therefore, inhibitors of these pathways are expected to sensitize cancer cells to a variety of drugs. This hypothesis was tested by analyzing the diversity of drugs that synergize with FDA-approved inhibitors of the proteasome, RNA synthesis, and Akt-mTOR pathways. Indeed, the quantitative evaluation indicates that inhibitors of any of these signaling pathways can synergize with a more diverse set of pharmaceuticals, compared to compounds inhibiting targets distinct from the “weak points” pathways. Our findings described here imply that inhibitors of the “weak points” pathways should be considered as primary candidates in a search for synergistic drug combinations.
Spatiotemporal Evolution of SARS-CoV-2 Alpha and Delta Variants during a Large Nationwide Outbreak in Vietnam, 2021
Authors: Tam Nguyen Thi , Anh Nguyen To , Tung Trinh Son , Thach Pham Ngoc , Dung Nguyen Thanh , Trang Van Dinh , Hung Le Manh , Dien Trinh Cong , Ngoc Nghiem My , Van Duyet Le , Cuong Phan Manh , Mai Phuong Hoang Vu , Thai Pham Quang , Nhu Tung Nguyen Le , Huy Man Dinh Nguyen , Phong Nguyen Thanh , Quang Vo Minh , Ngoc Thoa Pham Thi , Truong Nguyen Thanh , Phuong Thao Tran Nguyen , Linh Dao Phuong , Tai Ngo Tan , Bao Ho The , Vuong Vo Trong , Kim Nhung Huynh Thi , Dieu Hong Phan Nu , Phuoc Hanh Le Thi , Chung Le Thanh , Thanh Nhan Nguyen Thi , Thanh Ton That , Hung Do Thai , Mai Huynh Kim , Long Trinh Hoang , Trang Nguyen Thu , Hong Thuong Nguyen Thi , Thu Hong Nguyen Thi , Truc Nhu Le Nguyen , Han Ny Nguyen Thi , Thuy Cao Thu , Thanh Le Kim , Nguyet Lam Anh , Quynh Mai Le Thi , Thuong Tang Chi , Nga Le Hong , Thanh Tran Tan , Thwaites Guy , van Doorn H. Rogier , Van Vinh Chau Nguyen , Kesteman Thomas , Van Tan Le ,   OUCRU COVID-19 research group
Published: January 2023

In 2021, Vietnam experienced a large nationwide outbreak of COVID-19, with over 1.7 million infections and 32,000 deaths. We generated 1,303 SARS-CoV-2 whole-genome sequences, and mapped out the public health measures alongside the evolutionary trajectory of the pathogen. The Alpha variant caused sporadic outbreaks in early 2021 prior to the upsurge in cases associated with the Delta variant from June onward. The Delta variant outbreak was almost entirely confined to the AY.57 lineage, accounting for 99.2% of 1,212 Delta variant sequences, and resulting from a single introduction. Viral dispersal from the north, where it was first introduced into Vietnam, to the south, marked the start of the nationwide outbreak, with the south subsequently seeding the virus back to the other regions. Distinct AY.57 phylogenetic clusters in different regions of Vietnam were documented, pointing to the impact of in-country lockdown. Genomic surveillance is critical to inform pandemic response.
Plasma Microbial Cell-free DNA Sequencing from Over 15,000 Patients Identified a Broad Spectrum of Pathogens
Authors: Park Sarah Y. , Chang Eliza J , Ledeboer Nathan , Messacar Kevin , Lindner Martin S. , Venkatasubrahmanyam Shivkumar , Bercovici Sivan , Wilber Judith C. , Vaughn Marla Lay , Perkins Bradley A. , Nolte Frederick S.
Published: January 2023

Microbial cell-free DNA (mcfDNA) sequencing is an emerging infectious disease diagnostic tool which enables unbiased pathogen detection from plasma. The Karius Test®, a commercial mcfDNA sequencing assay developed by and available since 2017 from Karius, Inc. (Redwood City, CA), detects and quantifies mcfDNA as molecules/μl in plasma. The commercial sample data and results for all tests conducted from April 2018 through mid-September 2021 were evaluated for laboratory performance metrics, reported pathogens, and data from test requisition forms. A total of 18,690 reports were generated from 15,165 patients in a hospital setting among 39 states and the District of Columbia. The median time from sample receipt to reported result was 26 hours (IQR 25–28), and 96% of samples had valid test results. Almost two-thirds (65%) of patients were adults, and 29% at the time of diagnostic testing had ICD10 codes representing a diverse array of clinical scenarios. There were 10,752 (58%) reports that yielded at least one taxon for a total of 22,792 detections spanning 701 unique microbial taxa. The 50 most common taxa detected included 36 bacteria, 9 viruses, and 5 fungi. Opportunistic fungi (374Aspergillusspp., 258Pneumocystis jirovecii, 196Mucorales, and 33 dematiaceous fungi) comprised 861 (4%) of all detections. Additional diagnostically challenging pathogens (247 zoonotic and vector borne pathogens, 144Mycobacteria, 80Legionellaspp., 78 systemic dimorphic fungi, 69Nocardiaspp., and 57 protozoan parasites) comprised 675 (3%) of all detections. We report the largest cohort of patients tested using plasma mcfDNA sequencing. The wide variety of pathogens detected by plasma mcfDNA sequencing reaffirm our understanding of the ubiquity of some infections while also identifying taxa less commonly detected by conventional methods.
Risk factors for long COVID among healthcare workers, Brazil, 2020–2022
Authors: Marra Alexandre R. , Sampaio Vanderson Souza , Ozahata Mina Cintho , da Silva Rafael Lopes Paixão , Brito Anderson , Bragatte Marcelo , Kalil Jorge , Miraglia João Luiz , Malheiros Daniel Tavares , Guozhang Yang , Teich Vanessa Damazio , Victor Elivane da Silva , Pinho João Renato Rebello , Cypriano Adriana , Vieira Laura Wanderly , Polonio Miria , de Oliveira Solange Miranda , Ricardo Victória Catharina Volpe , Maezato Aline Miho , Callado Gustavo Yano , Schettino Guilherme de Paula Pinto , de Oliveira Ketti Gleyzer , Santana Rúbia Anita Ferraz , Malta Fernanda de Mello , Amgarten Deyvid , Boechat Ana Laura , Kobayashi Takaaki , Perencevich Eli , Edmond Michael B. , Rizzo Luiz Vicente
Published: January 2023

Objectives

We aimed to determine risk factors for the development of long coronavirus disease (COVID) in healthcare workers (HCWs).

Methods

We conducted a case-control study among HCWs who had confirmed COVID-19 infection working in a Brazilian healthcare system between March 1, 2020 and July 15, 2022. Cases were defined as those having long COVID per the Centers for Disease Control and Prevention definition. Controls were defined as HCWs who had documented COVID-19 infection but did not develop long COVID. Multiple logistic regression was used to assess the association between exposure variables and long COVID during 180 days of follow-up.

Results

Of 7,051 HCWs diagnosed with COVID-19 infection, 1,933 (27.4%) who developed long COVID were compared to 5,118 (72.6%) who did not. The majority of those with long COVID (51.8%) had 3 or more symptoms. Factors associated with development of long COVID were female sex (OR 1.21 [CI95 1.05-1.39]), age (OR 1.01 [CI95 1.00-1.02]), and two or more COVID-19 infections (1.27 [CI95 1.07-1.50]). Those infected with the Delta variant (OR 0.30 [CI95 0.17-0.50]) or the Omicron variant (OR 0.49 [CI95 0.30-0.78]), and those receiving four COVID-19 vaccine doses prior to infection (OR 0.05 [CI95 0.01-0.19]) were significantly less likely to develop long COVID.

Conclusions

Long COVID can be prevalent among HCWs. We found that acquiring more than one COVID-19 infection was a major risk factor for long COVID, while maintenance of immunity via vaccination was highly protective.
Deciphering microbiota of acute upper respiratory infections: a comparative analysis of PCR and mNGS methods for lower respiratory trafficking potential
Authors: Almas Sadia , Carpenter Rob E. , Singh Anuradha , Rowan Chase , Tamrakar Vaibhav K. , Sharma Rahul
Published: January 2023

Although it is clinically important for acute respiratory tract (co)infections to have rapid and accurate diagnosis, it is critical that respiratory medicine understand the advantages of current laboratory methods. In this study we tested nasopharyngeal samples (n=29) with a commercially available PCR assay and compared the results with hybridization capture-based mNGS workflow. Detection criteria for positive PCR samples was Ct<35 and for mNGS samples >40% target coverage, median depth of 1X and RPKM>10. A high degree of concordance (98.33% PPA and 100% NPA) was recorded. However, mNGS yielded positive 29 additional microorganisms (23 bacteria, 4 viruses, and 2 fungi) beyond PCR. We then characterize the microorganisms of each method into three phenotypic categories using the IDbyDNA Explify® Platform for consideration of infectivity and trafficking potential to the lower respiratory region. The findings are significant for providing a comprehensive yet clinically relevant microbiology profile of acute upper respiratory infection, especially important in immunocompetent respiratory cases or where traditional syndromic approaches fail to identify pathogenicity. Accordingly, this technology can be used to supplement current syndromic-based tests and data can quickly and effectively be phenotypically characterized for trafficking potential, clinical (co)infection, and comorbid consideration—with promise to reduce morbidity and mortality.

Highlights

What are the main findings?

Although there was a high concordance between methodologies, a hybridization capture-based mNGS workflow was able to detect 29 additional upper respiratory microorganisms versus PCR.

Identified microorganisms were rapidly characterized into three phenotypic groups for infectivity and trafficking potential.

What is the implication of the main finding?

A hybridization capture-based mNGS workflow can provide a comprehensive yet clinically relevant microbiology profile of acute upper respiratory infection

Deciphering upper respiratory microbiota with phenotypic grouping has potential to provide respiratory medicine a tool to better manage immunocompetent and complex respiratory cases.
Non-steroidal anti-inflammatories for analgesia in critically ill patients: a systematic review and meta-analysis of randomized control trials
Authors: Ma Chen-Hsiang , Tworek Kimberly B. , Kung Janice Y. , Kilcommons Sebastian , Wheeler Kathleen , Parker Arabesque , Senaratne Janek , Macintyre Erika , Sligl Wendy , Karvellas Constantine J. , Zampieri Fernando G , Kutsogiannis Demetrios Jim , Basmaji John , Lewis Kimberley , Chaudhuri Dipayan , Sharif Sameer , Rewa Oleksa G. , Rochwerg Bram , Bagshaw Sean M. , Lau Vincent I.
Published: January 2023

Purpose

While opioids are part of usual care for analgesia in the intensive care unit (ICU), there are concerns regarding excess use. This is a systematic review of non-steroidal anti-inflammatories (NSAIDs) use in critically ill adult patients.

Methods

We conducted a systematic search of MEDLINE, EMBASE, CINAHL, and Cochrane Library. We included randomized control trials (RCTs) comparing NSAIDs alone or as an adjunct to opioids for analgesia. The primary outcome was opioid utilization. We reported mean difference for continuous outcomes and relative risk for dichotomous outcomes with 95% confidence intervals (CIs). We evaluated study risk of bias using the Cochrane risk of bias tool and evidence certainty using GRADE.

Results

We included 15 RCTs (n=1621 patients). Adjunctive NSAID therapy to opioids reduced 24-hour oral morphine equivalent consumption by 21.4mg (95% CI: 11.8-31.0mg reduction, high certainty) and probably reduced pain scores (measured by visual analogue scale) by -6.1mm (95% CI: -12.2 to +0.1, moderate certainty). Adjunctive NSAIDs probably had no impact on duration of mechanical ventilation (-1.6 hours, 95% CI: -0.4 to -2.7 hours, moderate certainty) and may have no impact on ICU length of stay (-2.1 hours, 95% CI: -6.1 to +2.0 hours, low certainty). Variability in reporting of adverse outcomes (e.g. gastrointestinal bleeding, acute kidney injury) precluded their meta-analysis.

Conclusion

In critically ill adult patients, NSAIDs reduced opioid use, probably reduced pain scores, but were uncertain for duration of mechanical ventilation or ICU length of stay. Further research is required to characterize the prevalence of NSAID-related adverse outcomes.

Take-Home Message

In this systematic review and meta-analysis of 15 randomized control trials that included 1621 critically ill adult patients, the addition of non-steroidal anti-inflammatories to an opioid analgesic strategy reduced 24-hour opioid use and modestly reduced pain with no impact on duration of mechanical ventilation or ICU length of stay.
Alternative epidemic indicators for COVID-19: a model-based assessment of COVID-19 mortality ascertainment in three settings with incomplete death registration systems
Authors: McCabe Ruth , Whittaker Charles , Sheppard Richard J. , Abdelmagid Nada , Ahmed Aljaile , Alabdeen Israa Zain , Brazeau Nicholas F. , Abd Elhameed Abd Elhameed Ahmed , Bin-Ghouth Abdulla Salem , Hamlet Arran , AbuKoura Rahaf , Barnsley Gregory , Hay James A. , Alhaffar Mervat , Besson Emilie Koum , Saje Semira Mitiku , Sisay Binyam Girma , Gebreyesus Seifu Hagos , Sikamo Adane Petros , Worku Aschalew , Ahmed Yakob Seman , Mariam Damen Haile , Sisay Mitike Molla , Checchi Francesco , Dahab Maysoon , Endris Bilal Shikur , Ghani Azra C. , Walker Patrick G. T. , Donnelly Christl A. , Watson Oliver J.
Published: January 2023

Not all COVID-19 deaths are officially reported and, particularly in low-income and humanitarian settings the magnitude of such reporting gaps remain sparsely characterised. Alternative data sources, including burial site worker reports, satellite imagery of cemeteries and social-media-conducted surveys of infection, may offer solutions. By merging these data with independently conducted, representative serological studies within a mathematical modelling framework, we aim to better understand the range of under-reporting using the example of three major cities: Addis Ababa (Ethiopia), Aden (Yemen) and Khartoum (Sudan) during 2020. We estimate 69% - 100%, 0.8% - 8.0% and 3.0% - 6.0% of COVID-19 deaths were reported in these three settings, respectively. In future epidemics, and in settings where vital registrations systems are absent or limited, using multiple alternative data sources could provide critically-needed, improved estimates of epidemic impact. However, ultimately, functioning vital registration systems are needed to ensure that, in contrast to COVID-19, the impact of future pandemics or other drivers of mortality are reported and understood worldwide.

One sentence summary

We demonstrate the suitability of alternative data sources to assess the under-ascertainment of COVID-19 mortality.
Promoting Sleep Duration in the Pediatric Setting Using a Mobile Health Platform: A Randomized Optimization Trial
Authors: Mitchell Jonathan A. , Morales Knashawn H. , Williamson Ariel A. , Jawahar Abigail , Juste Lionola , Vajravelu Mary Ellen , Zemel Babette S. , Dinges David F. , Fiks Alexander G.
Published: January 2023

Objective

Determine the optimal combination of digital health intervention component settings that increase average sleep duration by ≥30 minutes per weeknight.

Methods

Optimization trial using a 25factorial design. The trial included 2 week run-in, 7 week intervention, and 2 week follow-up periods. Typically developing children aged 9-12y, with weeknight sleep duration <8.5 hours were enrolled (N=97). All received sleep monitoring and performance feedback. The five candidate intervention components (with their settings to which participants were randomized) were: 1) sleep goal (guideline-based or personalized); 2) screen time reduction messaging (inactive or active); 3) daily routine establishing messaging (inactive or active); 4) child-directed loss-framed financial incentive (inactive or active); and 5) caregiver-directed loss-framed financial incentive (inactive or active). The primary outcome was weeknight sleep duration (hours per night). The optimization criterion was: ≥30 minutes average increase in sleep duration on weeknights.

Results

Average baseline sleep duration was 7.7 hours per night. The highest ranked combination included the core intervention plus the following intervention components: sleep goal (either setting was effective), caregiver-directed loss-framed incentive, messaging to reduce screen time, and messaging to establish daily routines. This combination increased weeknight sleep duration by an average of 39.6 (95% CI: 36.0, 43.1) minutes during the intervention period and by 33.2 (95% CI: 28.9, 37.4) minutes during the follow-up period.

Conclusions

Optimal combinations of digital health intervention component settings were identified that effectively increased weeknight sleep duration. This could be a valuable remote patient monitoring approach to treat insufficient sleep in the pediatric setting.