bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel strategy for dynamic modeling of genome-scale interaction networks
Authors: Borzou Pooya , Ghaisari Jafar , Izadi Iman , Eshraghi Yasin , Gheisari Yousof
Published: February 2023

Motivation

The recent availability of omics data allows the construction of holistic maps of interactions between numerous role-playing biomolecules. However, these networks are often static, ignoring the dynamic behavior of biological processes. On the other hand, dynamic models are commonly constructed on small scales. Hence, the construction of large-scale dynamic models that can quantitatively predict the time-course cellular behaviors remains a big challenge.

Results

In this study, a pipeline is proposed for the automatic construction of large-scale dynamic models. The pipeline uses a list of biomolecules and their time-course trajectories in a given phenomenon as input. First, the interaction network of the biomolecules is constructed. To state the underlying molecular events of each interaction, it is translated into a map of biochemical reactions. Next, to define the kinetics of the reactions, an ordinary differential equation (ODE) is generated for each involved biomolecule. Finally, the parameters of the ODE system are estimated by a novel large-scale parameter approximation method. The high performance of the pipeline is demonstrated by modeling the response of a colorectal cancer cell line to different chemotherapy regimens. In conclusion, Systematic Protein Association Dynamic ANalyzer constructs genome-scale dynamic models, filling the gap between large-scale static and small-scale dynamic modeling strategies. This simulation approach allows for holistic quantitative predictions which are critical for the simulation of therapeutic interventions in precision medicine.

Availability and implementation

Detailed information about the constructed large-scale model of colorectal cancer is available in supplementary data. The SPADAN toolbox source code is also available on GitHub (https://github.com/PooyaBorzou/SPADAN).

Supplementary information

Supplementary data are available at Bioinformatics online.
scGCL: an imputation method for scRNA-seq data based on graph contrastive learning
Authors: Xiong Zehao , Luo Jiawei , Shi Wanwan , Liu Ying , Xu Zhongyuan , Wang Bo
Published: February 2023

Motivation

Single-cell RNA-sequencing (scRNA-seq) is widely used to reveal cellular heterogeneity, complex disease mechanisms and cell differentiation processes. Due to high sparsity and complex gene expression patterns, scRNA-seq data present a large number of dropout events, affecting downstream tasks such as cell clustering and pseudo-time analysis. Restoring the expression levels of genes is essential for reducing technical noise and facilitating downstream analysis. However, existing scRNA-seq data imputation methods ignore the topological structure information of scRNA-seq data and cannot comprehensively utilize the relationships between cells.

Results

Here, we propose a single-cell Graph Contrastive Learning method for scRNA-seq data imputation, named scGCL, which integrates graph contrastive learning and Zero-inflated Negative Binomial (ZINB) distribution to estimate dropout values. scGCL summarizes global and local semantic information through contrastive learning and selects positive samples to enhance the representation of target nodes. To capture the global probability distribution, scGCL introduces an autoencoder based on the ZINB distribution, which reconstructs the scRNA-seq data based on the prior distribution. Through extensive experiments, we verify that scGCL outperforms existing state-of-the-art imputation methods in clustering performance and gene imputation on 14 scRNA-seq datasets. Further, we find that scGCL can enhance the expression patterns of specific genes in Alzheimer’s disease datasets.

Availability and implementation

The code and data of scGCL are available on Github: https://github.com/zehaoxiong123/scGCL.

Supplementary information

Supplementary data are available at Bioinformatics online.
Equivariant estimation of Fréchet means
Authors: McCormack A , Hoff P D
Published: February 2023

The Fréchet mean generalizes the concept of a mean to a metric space setting. In this work we consider equivariant estimation of Fréchet means for parametric models on metric spaces that are Riemannian manifolds. The geometry and symmetry of such a space are partially encoded by its isometry group of distance-preserving transformations. Estimators that are equivariant under the isometry group take into account the symmetry of the metric space. For some models, there exists an optimal equivariant estimator, which will necessarily perform as well or better than other common equivariant estimators, such as the maximum likelihood estimator or the sample Fréchet mean. We derive the general form of this minimum risk equivariant estimator and in a few cases provide explicit expressions for it. A result for finding the Fréchet mean for distributions with radially decreasing densities is presented and used to find expressions for the minimum risk equivariant estimator. In some models the isometry group is not large enough relative to the parametric family of distributions for there to exist a minimum risk equivariant estimator. In such cases, we introduce an adaptive equivariant estimator that uses the data to select a submodel for which there is a minimum risk equivariant estimator. Simulation results show that the adaptive equivariant estimator performs favourably relative to alternative estimators.
Large-scale transient peri-ictal perfusion magnetic resonance imaging abnormalities detected by quantitative image analysis
Authors: Köstner Manuel , Rebsamen Michael , Radojewski Piotr , Rummel Christian , Jin Baudouin , Meier Raphael , Ahmadli Uzeyir , Schindler Kaspar , Wiest Roland
Published: February 2023

Epileptic seizures require a rapid and safe diagnosis to minimize the time from onset to adequate treatment. Some epileptic seizures can be diagnosed clinically with the respective expertise. For more subtle seizures, imaging is mandatory to rule out treatable structural lesions and potentially life-threatening conditions. MRI perfusion abnormalities associated with epileptic seizures have been reported in CT and MRI studies. However, the interpretation of transient peri-ictal MRI abnormalities is routinely based on qualitative visual analysis and therefore reader dependent. In this retrospective study, we investigated the diagnostic yield of visual analysis of perfusion MRI during ictal and postictal states based on comparative expert ratings in 51 patients. We further propose an automated semi-quantitative method for perfusion analysis to determine perfusion abnormalities observed during ictal and postictal MRI using dynamic susceptibility contrast MRI, which we validated on a subcohort of 27 patients. The semi-quantitative method provides a parcellation of 3D T1-weighted images into 32 standardized cortical regions of interests and subcortical grey matter structures based on a recently proposed method, direct cortical thickness estimation using deep learning–based anatomy segmentation and cortex parcellation for brain anatomy segmentation. Standard perfusion maps from a Food and Drug Administration–approved image analysis tool (Olea Sphere 3.0) were co-registered and investigated for region-wise differences between ictal and postictal states. These results were compared against the visual analysis of two readers experienced in functional image analysis in epilepsy. In the ictal group, cortical hyperperfusion was present in 17/18 patients (94% sensitivity), whereas in the postictal cohort, cortical hypoperfusion was present only in 9/33 (27%) patients while 24/33 (73%) showed normal perfusion. The (semi-)quantitative dynamic susceptibility contrast MRI perfusion analysis indicated increased thalamic perfusion in the ictal cohort and hypoperfusion in the postictal cohort. Visual ratings between expert readers performed well on the patient level, but visual rating agreement was low for analysis of subregions of the brain. The asymmetry of the automated image analysis correlated significantly with the visual consensus ratings of both readers. We conclude that expert analysis of dynamic susceptibility contrast MRI effectively discriminates ictal versus postictal perfusion patterns. Automated perfusion evaluation revealed favourable interpretability and correlated well with the classification of the visual ratings. It may therefore be employed for high-throughput, large-scale perfusion analysis in extended cohorts, especially for research questions with limited expert rater capacity.
Caloric restriction for the immunometabolic control of human health
Authors: Procaccini Claudio , de Candia Paola , Russo Claudia , De Rosa Giusy , Lepore Maria Teresa , Colamatteo Alessandra , Matarese Giuseppe
Published: February 2023

Nutrition affects all physiological processes occurring in our body, including those related to the function of the immune system; indeed, metabolism has been closely associated with the differentiation and activity of both innate and adaptive immune cells. While excessive energy intake and adiposity have been demonstrated to cause systemic inflammation, several clinical and experimental evidence show that calorie restriction (CR), not leading to malnutrition, is able to delay aging and exert potent anti-inflammatory effects in different pathological conditions. This review provides an overview of the ability of different CR-related nutritional strategies to control autoimmune, cardiovascular, and infectious diseases, as tested by preclinical studies and human clinical trials, with a specific focus on the immunological aspects of these interventions. In particular, we recapitulate the state of the art on the cellular and molecular mechanisms pertaining to immune cell metabolic rewiring, regulatory T cell expansion, and gut microbiota composition, which possibly underline the beneficial effects of CR. Although studies are still needed to fully evaluate the feasibility and efficacy of the nutritional intervention in clinical practice, the experimental observations discussed here suggest a relevant role of CR in lowering the inflammatory state in a plethora of different pathologies, thus representing a promising therapeutic strategy for the control of human health.
Race Theory versus a Religious World-View: SS–Ustaša Relations and Islam in the Independent State of Croatia
Authors: Bartulin Nevenko
Published: February 2023

This article analyses SS policy toward the Bosnian Muslims of the Independent State of Croatia (NDH) within the context of the ideological and political relationship between the German Reich and the Ustaša regime. As part of its broader aim of mobilising Muslim support for Germany during the Second World War, the SS adopted and pursued a pan-Islamic policy in its effort to recruit Muslim soldiers for the Croatian-Bosnian Waffen-SS Handschar Division. Although the SS officially regarded the Bosnian Muslims as ‘Croats of the Islamic faith’ and Aryans, SS propaganda focused on the appeal to religious sentiments and treated them primarily as members of a global Islamic community. This unique pan-Islamic policy was the product not only of broader geopolitical aims that arose in reaction to wartime exigencies but also a widespread Nazi Islamophilic attitude that was combined with the anti-Catholic ideology characteristic of the SS leadership. The SS’s pro-Islamic policy actually undermined one of the main political-ideological aims of the Ustaša government, namely, the integration of the Bosnian Muslims into the Aryan-Croatian ‘national community’. Contrary to the widespread historiographical view that the Ustaše were a politically Catholic movement, this article highlights the fact that they adhered to a clearly secular racial-nationalist ideology, while the SS exaggerated the influence of clericalism in the NDH. Historiographical accounts of SS policy toward Islam in the Balkans have tended to play down the role of the Ustaše and Nazi anti-Catholicism, even though a more thorough analysis of SS-Ustaša relations can shed more light, as this article shows, on the precise nature of the relationship between race and religion in National Socialist ideology.
The legacies of war for Ukraine
Authors: Munroe Ellen , Nosach Anastasiia , Pedrozo Moisés , Guarnieri Eleonora , Riaño Juan Felipe , Tur-Prats Ana , Valencia Caicedo Felipe
Published: February 2023

This article reviews the literature on the multifaceted consequences of historical conflict. We revisit three key topics, which are especially relevant for the current Ukrainian context. (1) The negative long-term impact of bombing campaigns and political repression against civilians. (2) The interplay between forced migration, refugees and war. (3) The role of gender and war, with a special focus on sex ratios and conflict-related sexual violence. We conclude with an empirical investigation of the Russian war against Ukraine, including aforementioned historical determinants such as ethnic populations, historical political repression and voting outcomes.
Social Security Reform and the Untapped Potential of Human Rights Law
Authors: Rowe Christopher
Published: February 2023

The courts have done little to ameliorate the harsh ‘austerity’ reforms pursued by the government since 2010, adopting a highly deferential approach towards human rights claims in the social security context. This article identifies the two key moves to achieve this result: adopting the manifestly without reasonable foundation standard of justification and treating indirect discrimination claims on suspect grounds as not ‘real’ discrimination claims. It shows nonetheless the untapped potential of Convention rights, since even within this framework strong arguments were still available to the courts, based on the functioning of the social security system, which should have rendered two of the harshest reforms, the two-child limit and especially the benefit cap, Convention incompatible. The cap, which limits the subsistence benefits of unemployed families, is justified as a work-incentive policy, yet through Universal Credit the state also independently assesses families affected by the cap as doing all that they reasonably can to find work.
Bypassing the Incumbent: Leadership Tenure and Foreign Aid Channels
Authors: Allen Susan Hannah , Ferry Lauren Lee , Shammama Obaida
Published: February 2023

The traditional perception is that foreign aid provides leaders in recipient states access to nontax revenue, which incumbents may be able to manipulate in order to provide public or private goods as is required to maintain office. Recognizing this possibility, donors have been shifting away from direct government-to-government aid and toward bypass aid, administered by NGOs and civil society groups rather than the regime directly. Receiving aid through alternative channels is designed to increase aid’s effectiveness, yet it has potential implications for incumbent leaders who may have less ability to manipulate aid receipts to their benefit. In this paper, we argue that bypass aid should negatively affect leaders’ tenure, conditional on the political institutions in place. Using data on bypass aid from 2004 to 2017, we find evidence of a punishing effect and conclude that bypass aid is a particularly acute problem for leaders in authoritarian regimes. The findings imply that efficiency and stability may present a tradeoff for potential donors and that bypass aid may not be the panacea of the aid effectiveness movement.
Development and validation of a one-tube, nested real-time PCR method suitable for routine detection ofMycobacterium bovisin animal tissue
Authors: Morris Rowan P , Montoya Teresa , Price Natasha , Nicklin Babita , Hogarth Philip J , Mayers Jo , Sawyer Jason , McGoldrick Adrian
Published: February 2023

Aims

Development and validation of a real-time PCR test for high-throughput routine screening of animal tissue for Mycobacterium bovis and other Mycobacterium tuberculosis complex (MTBC) members.

Methods and results

A preliminary study compared the results of a combination of five tissue preparation/DNA extraction methods and nine PCR assays on a panel of 92 cattle tissue samples of known M. bovis culture status (55 positive and 37 negative). The combination of DNA extraction and PCR was found to be important in achieving optimal detection of M. bovis. The optimal combination of a simple tissue preparation/DNA extraction method and a one-tube, nested real-time PCR to maximize the sensitivity of detection of an M. bovis-specific RD4 deletion and an IS1081 MTBC-specific target was selected for further evaluation. In total, tissue samples collected from 981 cattle and 366 non-bovine animals and submitted for routine TB culture were parallel tested with the selected method, as well as tissue samples obtained from 156 animals in certified TB-free cattle herds.

Conclusion

For cattle, the optimized RD4-IS1081 PCR test exhibited a diagnostic sensitivity of 96% (95% CI: 94–97%) and specificity of 97% (95% CI: 95–98%) compared to culture. Specificity was 100% when testing the 156 samples from known TB-free cattle. For non-bovine species, the PCR had a diagnostic sensitivity of 93% (95% CI: 83–98%) and a specificity of 99% (95% CI: 97–100%).
A CRISPR/Cas12a-Mediated Sensitive DNA Detection System for Gene-Edited Rice
Authors: Wang Zhi , Huang Chunmeng , Wei Shuang , Zhu Pengyu , Li Yiming , Fu Wei , Zhang Yongjiang
Published: February 2023

Background

In recent years, genome editing technology represented by clustered regularly interspaced short palindromic repeat/CRISPR-associated nuclease 9 （CRISPR/Cas9） has been developed and applied in transgenic research and development, and transgenic products have been developed for a variety of applications. Gene editing products, unlike traditional genetically modified crops, which are generally obtained by target gene deletion, insertion, base mutation, etc., may not differ significantly at the gene level from conventional crops, which increases the complexity of testing.

Objective

We established a specific and sensitive CRISPR/Cas12a-mediated gene editing system to detect target fragments in a variety of transgenic rice lines and commercial rice-based processing products.

Methods

In this study, the CRISPR/Cas12a visible detection system was optimized for the visualization of nucleic acid detection in gene-edited rice. The fluorescence signals were detected by both gel electrophoresis and fluorescence-based methods.

Results

The detection limit of the CRISPR/Cas12a detection system established in this study was more precise, especially for low-concentration samples. In addition to achieving single-base detection in gene-edited rice, we showed that different base mutations in the target sequence have different detection efficiencies by sitewise variant compact analysis. The CRISPR/Cas12a system was verified via a common transgenic rice strain and commercial rice sources. The results proved that the detection method could not only be tested in samples with multiple mutation types but could also effectively detect target fragments in commercial rice products.

Conclusion

We have developed a set of efficient detection methods with CRISPR/Cas12a for gene-edited rice detection to provide a new technical basis for rapid field detection of gene-edited rice.

Highlights

The CRISPR/Cas12a-mediated visual detection method used to detect gene-edited rice was evaluated for its specificity, sensitivity, and robustness.
Adventive Population ofTrissolcus japonicus(Hymenoptera: Scelionidae), Parasitoid ofHalyomorpha halys(Hemiptera: Pentatomidae), Discovered in Southwestern Idaho
Authors: Richardson Kate V , Alston Diane G , Spears Lori R
Published: February 2023

Adventive populations of Trissolcus japonicus (Ashmead) have been detected in the eastern and western United States including the western states of Washington, Oregon, California, and Utah. These populations may provide classical biological control for the invasive brown marmorated stink bug, Halyomorpha halys (Stål), which can cause economic loss to many specialty crops in western North America. Idaho has not previously been surveyed for the exotic T. japonicus or native parasitoids of H. halys. In July 2021, T. japonicus was discovered emerging from wild H. halys egg masses in Star, Idaho (43.69788, −116.49427), and was detected on yellow sticky cards from July to September. This is the first record of T. japonicus in the state of Idaho. T. japonicus constituted only a small portion of Trissolcus species detected; other species included T. euschisti (Ashmead), T. hullensis (Harrington), and T. utahensis (Ashmead). Genetic population level analysis of T. japonicus specimens from Idaho supports the likelihood of its expansion inland from the west coast, inhabiting ecozones previously considered unsuitable due to high temperatures and low humidity. This report opens the prospect of an effective biological control agent for H. halys in Idaho and potentially other hot and dry geographic regions and expands documentation of the presence of adventive T. japonicus populations in North America.
Designing to detect heteroscedasticity in a regression model
Authors: Lanteri Alessandro , Leorato Samantha , López-Fidalgo Jesús , Tommasi Chiara
Published: February 2023

We consider the problem of designing experiments to detect the presence of a specified heteroscedastity in Gaussian regression models. We study the relationship of the Ds- and KL-criteria with the noncentrality parameter of the asymptotic chi-squared distribution of a likelihood-based test, for local alternatives. We found that, when the heteroscedastity depends on one parameter, the two criteria coincide asymptotically and that the D1-criterion is proportional to the noncentrality parameter. Differently, when it depends on several parameters, the KL-optimum design converges to the design that maximizes the noncentrality parameter. Our theoretical findings are confirmed through a simulation study.
A spatial stochastic frontier model introducing inefficiency spillovers
Authors: Galli Federica
Published: February 2023

This paper develops a spatial Durbin stochastic frontier model for panel data introducing spillover effects in the determinants of technical efficiency (SDF-STE). The model nests several existing spatial and non-spatial stochastic frontier specifications and is estimated using maximum-likelihood techniques. Estimates are shown to be unbiased even for small sample sizes and for alternative specifications of the spatial weight matrix implementing different Monte Carlo simulations. Finally, an application to the Italian accommodation sector is provided. Empirical findings suggest the relevance of the SDF-STE model in capturing labour productivity and knowledge spillover effects.
Incidental contrast opacification of the appendix secondary to urological intervention
Authors: Hunn Samuel , Winston Joshua , Davies Nicholas
Published: February 2023

A 23-year-old otherwise well male, with right ureteric stent in situ placed electively for a 9-mm symptomatic pelviureteric junction stone underwent a right ureteropyeloscopy, retrograde pyelogram laser lithotripsy and stent exchange for stone clearance. The procedure was uncomplicated. Following stent removal on day 2, the patient developed acute right lower quadrant pain, which was investigated with non-contrast CT abdomen. The scan demonstrated a contrast-filled vermiform appendix, secondary to vicarious contrast excretion. This case report describes a rare manifestation of vicarious contrast excretion and explains this phenomenon.
Incidental ectopic adrenal cortical tissue in the descending mesocolon in an elderly female: a first case report in the literature
Authors: Al-janabi Moatasem Hussein , Allan Ali , Salloum Rabab
Published: February 2023

Ectopic adrenal tissue (EAT) is an extremely unusual finding. The most common site is the genitourinary tract and pelvis, and more frequently in males than females. In our report, we discuss an ectopic adrenal cortical tissue detected in the descending mesocolon in an elderly female. To the best of our knowledge, this case is the first report in the English literature.
Journey of a stone—thirty years on
Authors: Nan Xinyi , Prabha Ramesh Damodaran , Rashid Muddassir , Patel Bhavik
Published: February 2023

Laparoscopic cholecystectomy is the gold standard surgical treatment of gallstone disease and a commonly performed procedure in general surgery. Retained gallstones from intraoperative spillage remain largely asymptomatic and complications are rare. Peak incidence of presentation occurs within a year; however, it is important to recognize retained gallstones as a differential for acute presentations even many years postoperatively. We present the case of a 74-year-old female who presented with a retained-gallstone-associated abdominal wall abscess 30 years after spillage during the original surgery, which was successfully treated with a stepwise extraperitoneal approach with local drainage.
Repurposing for the just transition: energy companies need to future-proof their structure and strategy
Authors: Heffron Raphael J
Published: February 2023

In order to achieve a just transition to a low-carbon economy, there is a need for large-scale and far-reaching organizational reform. In particular, this needs to happen with multi-national and state-owned energy companies. These firms play a key role in societies worldwide today, however, they are ignoring or neglecting their role in the energy transition and the wider movement towards achieving a low-carbon economy in a ‘just’ way. These companies are transitioning far too slowly and the rhetoric they advance is now outdated given the current market and societal dynamics. Early indications are that Governments and the public remain willing to assist in financing the transitioning of these companies. However, this support will have a time limit. This short brief focuses on the need for these companies to ‘repurpose’ themselves, to obtain requisite data for their decision-making and begin future-proofing their strategies which includes themselves individually also.
Understanding the origin of CEMP – no stars through ultra-faint dwarfs
Authors: Rossi Martina , Salvadori Stefania , Skúladóttir Ása , Vanni Irene
Published: February 2023

The origin of Carbon Enhanced Metal-Poor (CEMP-no) stars with low abundances of neutron-capture elements is still unclear. These stars are ubiquitous, found primarily in the Milky Way halo and ultra-faint dwarf galaxies (UFDs). To make a major step forward, we developed a data-calibrated model for Böotes I that simultaneously includes all carbon sources: supernovae and asymptotic giant branch (AGB) stars both from first (Pop III) stars, and subsequent normal star formation (Pop II). We demonstrate that each of these sources leaves a specific chemical signature in the gas, allowing us to identify the origin of present day CEMP-no stars through their location in the A(C)–[Fe/H] diagram. The CEMP stars with A(C) > 6 are predominantly enriched by AGB Pop II stars. We identify a new class of moderate CEMP-s stars with A(C) ∼7 and 0 < [Ba/Fe] < + 1, imprinted by winds from AGB stars. True Pop III descendants are predicted to have A(C) < 6 and a constant [C/Mg] with [Fe/H], in perfect agreement with observations in Böotes I and the Milky Way halo. For the first time we now have a complete picture of the origins of CEMP-no stars which can and will be verified with future observations.
CAS Array: design and assessment of a genotyping array for Chinese biobanking
Authors: Tian Zijian , Chen Fei , Wang Jing , Wu Benrui , Shao Jian , Liu Ziqing , Zheng Li , Wang You , Xu Tao , Zhou Kaixin
Published: February 2023

Background

Chronic diseases are becoming a critical challenge to the aging Chinese population. Biobanks with extensive genomic and environmental data offer opportunities to elucidate the complex gene–environment interactions underlying their aetiology. Genome-wide genotyping array remains an efficient approach for large-scale genomic data collection. However, most commercial arrays have reduced performance for biobanking in the Chinese population.

Materials and methods

Deep whole-genome sequencing data from 2 641 Chinese individuals were used as a reference to develop the CAS array, a custom-designed genotyping array for precision medicine. Evaluation of the array was performed by comparing data from 384 individuals assayed both by the array and whole-genome sequencing. Validation of its mitochondrial copy number estimating capacity was conducted by examining its association with established covariates among 10 162 Chinese elderly.

Results

The CAS Array adopts the proven Axiom technology and is restricted to 652 429 single-nucleotide polymorphism (SNP) markers. Its call rate of 99.79% and concordance rate of 99.89% are both higher than for commercial arrays. Its imputation-based genome coverage reached 98.3% for common SNPs and 63.0% for low-frequency SNPs, both comparable to commercial arrays with larger SNP capacity. After validating its mitochondrial copy number estimates, we developed a publicly available software tool to facilitate the array utility.

Conclusion

Based on recent advances in genomic science, we designed and implemented a high-throughput and low-cost genotyping array. It is more cost-effective than commercial arrays for large-scale Chinese biobanking.
Inverse mass ordering of light scalar mesons in the Nambu–Jona-Lasinio model
Authors: Saionji Takahiro , Jido Daisuke , Harada Masayasu
Published: February 2023

The masses of the low-lying scalar mesons are investigated in the three-flavor Nambu–Jona-Lasinio (NJL) model by treating the scalar mesons as composite objects of a quark and an antiquark. It is known that a simple $\bar{q}q$ picture fails to reproduce the so-called inverse mass ordering for the scalar mesons. Recently a new mechanism to reproduce the observed mass spectrum of the scalar mesons was proposed in a linear sigma model by introducing flavor symmetry breaking induced by the U(1) axial anomaly. Motivated by this proposal, we examine whether this new mechanism also works in the NJL model. By calculating the scalar meson masses, we find that the NJL model reproduces the observed mass ordering with sufficient strength of the new term. With this mechanism, it turns out that the constituent strange quark mass becomes degenerate to that of the up and down quarks if the inverse mass ordering is reproduced. We also discuss the scalar diquark masses to check the consistency of the degeneracy of the constituent quark masses with the light baryon masses.
Exploring Microbial Dysbiosis in Orchards Affected by Little Cherry Disease
Authors: Yurgel Svetlana N. , Sallato C. Bernardita , Cheeke Tanya E.
Published: February 2023

The phytoplasma ‘ Candidatus Phytoplasma pruni’, a causative agent of little cherry disease (LCD), has become an increasing problem for sweet cherry growers in Washington State, which is the largest producer of cherry fruit in the United States. The control of LCD currently relies on the identification and removal of infected trees, which has proven to be difficult because of the prolonged asymptomatic but still contagious state of the disease, and the lack of reliable and economical tests. Thus, the development of new approaches for early detection of LCD will be an important step in the successful control of this tree fruit disease. To identify potential microbial indicators of ‘ Ca. P. pruni’ infection, we evaluated the bacterial and fungal communities in the roots of cherry trees from two different orchards that were (i) infected with ‘ Ca. P. pruni’ and symptomatic; (ii) infected with ‘ Ca. P. pruni’ but remained asymptomatic; and (iii) healthy, with non-‘ Ca. P. pruni’-infected trees. We found significant variation in the microbiomes between the two cherry orchards, with the location being a stronger driving factor determining the fungal compared with the bacterial community. The fungal communities were less affected by the disease conditions compared with the bacterial microbiome. Overall, this study demonstrates the feasibility of the microbiome approach for the early detection of LCD caused by ‘ Ca. P. pruni’ but also demonstrates that more orchards need to be sampled because location was a stronger contributor to the microbiome of cherry tree roots than disease condition.
Resistance to QoI and DMI Fungicides Does Not Reduce Virulence of C. beticola Isolates in North Central United States
Authors: Liu Yangxi , Del Rio Mendoza Luis E. , Qi Aiming , Lakshman Dilip , Bhuiyan M. Z. R. , Wyatt Nathan , Neubauer Jonathan , Bolton Melvin , Khan Mohamed F. R.
Published: February 2023

Cercospora leaf spot (CLS) is a destructive disease limiting sugar beet production and is managed using resistant cultivars, crop rotation, and timely applications of effective fungicides. Since 2016, its causal agent, Cercospora beticola, has been reported to be resistant to quinone outside inhibitors (QoIs) and to have reduced sensitive to demethylation inhibitors (DMIs) in sugar beet growing areas in North Dakota and Minnesota. Isolates of C. beticola resistant to QoIs, DMIs, and both QoIs and DMIs were collected from fields in Foxhome, Minnesota, in 2017. Fitness of these resistant isolates was compared with that of QoI- and DMI-sensitive isolates in laboratory and greenhouse studies. In the lab, mycelial growth, spore production, and spore germination were measured. The results showed that resistant isolates had significantly less mycelial growth and spore production than sensitive isolates, while no significant difference in spore germination was detected. In the greenhouse, six leaf-stage sugar beets were inoculated with a spore suspension made from each resistant group and incubated in separate humidity chambers. CLS disease severity was evaluated visually at 7, 14, and 21 days after inoculation (DAI), and the areas under disease progress curve (AUDPC) were calculated. Resistant isolates had significantly smaller AUDPC but still caused as high disease severity as the sensitive ones at 21 DAI. Although QoI- and/or DMI-resistant isolates had a relatively slower disease development, they still caused high disease severity and need to be factored in disease management practices.
Targeting XBP1 mRNA splicing sensitizes glioblastoma to chemotherapy
Authors: Dowdell Amiee , Marsland Mark , Faulkner Sam , Gedye Craig , Lynam James , Griffin Cassandra P. , Marsland Joanne , Jiang Chen Chen , Hondermarck Hubert
Published: February 2023

Glioblastoma (GBM) is the most frequent and deadly primary brain tumor in adults. Temozolomide (TMZ) is the standard systemic therapy in GBM but has limited and restricted efficacy. Better treatments are urgently needed. The role of endoplasmic reticulum stress (ER stress) is increasingly described in GBM pathophysiology. A key molecular mediator of ER stress, the spliced form of the transcription factor x‐box binding protein 1 (XBP1s) may constitute a novel therapeutic target; here we report XBP1s expression and biological activity in GBM. Tumor samples from patients with GBM (n = 85) and low‐grade glioma (n = 20) were analyzed by immunohistochemistry for XBP1s with digital quantification. XBP1s expression was significantly increased in GBM compared to low‐grade gliomas. XBP1s mRNA showed upregulation by qPCR analysis in a panel of patient‐derived GBM cell lines. Inhibition of XBP1 splicing using the small molecular inhibitor MKC‐3946 significantly reduced GBM cell viability and potentiated the effect of TMZ in GBM cells, particularly in those with methylated O6‐methylguanine‐DNA methyl transferase gene promoter. GBM cells resistant to TMZ were also responsive to MKC‐3946 and the long‐term inhibitory effect of MKC‐3946 was confirmed by colony formation assay. In conclusion, this data reveals that XBP1s is overexpressed in GBM and contributes to cancer cell growth. XBP1s warrants further investigation as a clinical biomarker and therapeutic target in GBM.
Comparison of Single-level Cervical Radiculopathy Outcomes Between Posterior Endoscopic Cervical Decompression and Anterior Cervical Discectomy and Fusion
Authors: Chen Yuanyuan , Zhang Tao , Cai Bin , Xu Jianguang , Lian Xiaofeng
Published: February 2023

Study Design:

A retrospective cohort study.

Objective:

To investigate the mid-term results and technical possibilities of posterior endoscopic cervical decompression (PECD) in the treatment of cervical radiculopathy.

Summary of Background Data:

PECD has been used in the treatment of cervical radiculopathy for the past decades; there is a paucity of studies directly comparing its outcomes with anterior cervical discectomy and fusion (ACDF) for patients with single-level cervical radiculopathy.

Patients and Methods:

From January 2016 to December 2018, clinical and radiologic data of 42 patients were collected. Patients were followed for a mean of 40.6 months (range: 30–54 mo) after surgery. Changes in cervical lordosis and degeneration of adjacent segments were analyzed. Dysphagia was assessed using the Bazaz score, and clinical outcomes were analyzed using the Neck Disability Index and visual analog scoring system.

Results:

There were no significant differences in neurological outcomes between the two groups. Significant between-group differences in postoperative dysphagia were observed (P < 0.05). There were significant differences in postoperative segmental Cobb angles and disc height between the two groups (P < 0.05). Degenerative changes in the adjacent segments occurred in 5 patients in the ACDF group and 1 patient in the PECD group (P < 0.05); no revision surgery was needed.

Conclusions:

Clinical outcomes of PECD for patients with unilateral radiculopathy were satisfactory. On the premise of a strict selection of indications, we consider this technique to be a safe supplement and alternative to ACDF for patients with unilateral cervical radiculopathy. Longer follow-up periods are required to confirm these observations.
Residual Neuropathic Pain in Postoperative Patients With Cervical Ossification of Posterior Longitudinal Ligament
Authors: Miyagi Masayuki , Inoue Gen , Yoshii Toshitaka , Egawa Satoru , Sakai Kenichiro , Kusano Kazuo , Nakagawa Yukihiro , Hirai Takashi , Wada Kanichiro , Katsumi Keiichi , Kimura Atsushi , Furuya Takeo , Nagoshi Narihito , Kanchiku Tsukasa , Nagamoto Yukitaka , Oshima Yasushi , Nakashima Hiroaki , Ando Kei , Takahata Masahiko , Mori Kanji , Nakajima Hideaki , Murata Kazuma , Matsunaga Shunji , Kaito Takashi , Yamada Kei , Kobayashi Sho , Kato Satoshi , Ohba Tetsuro , Inami Satoshi , Fujibayashi Shunsuke , Katoh Hiroyuki , Kanno Haruo , Koda Masao , Takahashi Hiroshi , Ikeda Shinsuke , Imagama Shiro , Kawaguchi Yoshiharu , Takeshita Katsushi , Matsumoto Morio , Takaso Masashi , Okawa Atsushi , Yamazaki Masashi
Published: February 2023

Study Design:

A prospective multi-institutional observational study.

Objective:

To investigate and identify risk factors for residual neuropathic pain after surgery in patients with cervical ossification of posterior longitudinal ligament (c-OPLL).

Summary of Background Data:

Patients with c-OPLL often require surgery for numbness and paralysis of the extremities; however, postoperative neuropathic pain can considerably deteriorate their quality of life.

Methods:

Out of 479 patients identified from multicenter c-OPLL registries between 2014 and 2017, 292 patients who could be followed up for 2 years postoperatively were reviewed, after excluding patients with nervous system comorbidities. Demographic details; medical history; radiographic factors including the K-line, spinal canal occupancy rate of OPLL, cervical kyphosis angle, and presence of spinal cord myelomalacia; preoperative Japanese Orthopaedic Association (JOA) score; surgical procedure (fusion or decompression surgery); postoperative neurological deterioration; and the visual analogue scale for pain and numbness in the upper extremities (U/E) or trunk/lower extremities (L/E) at baseline and at 2 years postoperatively were assessed. Patients were grouped into residual and non-residual groups based on a postoperative visual analogue scale ≥40 mm. Risk factors for residual neuropathic pain were evaluated by multiple logistic regression analysis.

Results:

The prevalence of U/E and L/E residual pain in postoperative c-OPLL patients was 51.7% and 40.4%, respectively. The U/E residual group had a poor preoperative JOA score and longer illness duration, and fusion surgery was more common in the residual group than in non-residual group. The L/E residual group was older with a poorer preoperative JOA score. On multivariate analysis, risk factors for U/E residual pain were long illness duration and poor preoperative JOA score, whereas those for L/E residual pain were age and poor preoperative JOA score.

Conclusions:

The risk factors for residual spinal neuropathic pain after c-OPLL surgery were age, long duration of illness, and poor preoperative JOA score.

Level of Evidence:

IV
Short-Term Outcomes of Neuromuscular Electrical Stimulation in Critically Ill Patients
Authors: Mahran Ghada S. K. , Mehany Mogeda M. , Abbas Mostafa S. , Shehata Abd-ElRady , AbdElhafeez Azza S. , Obiedallah Ahmed A. , Mohamed Sherif A.
Published: February 2023

Muscle weakness acquired in the intensive care unit (ICU) adversely affects outcomes of ICU patients. This article reports the short-term respiratory effects of neuromuscular electrical stimulation (NMES) in critically ill patients. Patients were randomly assigned to an intervention group (NMES + conventional physiotherapy) and a control group (sham NMES + conventional physiotherapy). The application of NMES in the intervention group resulted in a significant decrease in the duration of mechanical ventilation and reduced the number of weaning trial failures. Other positive outcomes included reductions in the length of ICU stays and decreased mortality when compared with the control group.
Electrolyte Imbalance Among Patients With and With No ST-Elevation Myocardial Infarction
Authors: Dreidi Mu'taz , Asmar Imad , Jaghama Maram , Alrimawi Intima , Atout Maha
Published: February 2023

Electrolytes imbalances are highly prevalent and have shown a high impact on mortality in patients with acute myocardial infarction. These electrolytes imbalance have prognostic value in predicting mortality in patients with acute myocardial infarction. The purpose of this study was to assess the prognostic value of electrolyte imbalances in predicting 1-month mortality among patients with myocardial infarction with and with no ST-elevation. This cohort study was conducted in a referral hospital in the West Bank, Palestine. All patients with confirmed medical diagnosis of acute myocardial infarction and admitted to the medical coronary care unit in the hospital were eligible participants. A convenience sample of 186 participants was obtained. These participants were followed up for 1 month to assess their survival (alive or dead). Demographic and clinical data were recorded by reviewing their health records. The derived data were analyzed using SPSS version 19. About 36% of all patients were found to be hyponatremic, 15% of them have hypokalemia, and 9% of patients had hypocalcemia. There was a significant difference between STEMI and non-STEMI in sodium (t = 4.7, P < .001). A multivariate logistic regression analysis was performed to predict 1-month mortality for patients with myocardial infarction with and with no ST-elevation. The predictors that were found to be significant are sodium (odds ratio [OR] = 0.789, P = .010), calcium (OR = 0.221, P = .014), diastolic blood pressure (OR = 0.933, P = .047), and blood urea nitrogen (OR = 0.821, P = .005). Electrolyte imbalance was highly prevalent among patients with acute myocardial infarction. Hyponatremia and hypocalcemia were present and associated significantly with predicting 1-month mortality. Health care providers should take into consideration the electrolytes of patients with acute myocardial infarction from the first moment of admission and correct them early to maximize the clinical outcomes and survival for patients.
Nursing Students' Understanding of Palliative Care in Palestine
Authors: Salameh Basma , Ayed Ahmad , Fashafsheh Imad , Alrazeeni Daifallah M. , Batran Ahmed , Ahmed Fadia
Published: February 2023

Palliative care is a method of preventing and alleviating suffering for patients who have been diagnosed with terminal diseases by early detection, accurate assessments, and pain and symptom management. Patients and their families can then mitigate related physical, psychological, and spiritual challenges and thus will have a better quality of life. This article reports a study that evaluated undergraduate nursing students' knowledge of and attitude and self-efficacy toward palliative and end-of-life care in Palestine. A descriptive, cross-sectional design was used among a convenience sample of 449 undergraduate nursing students at the end of their second, third, and fourth years. The results of this research revealed that nursing students had low levels of knowledge about palliative care and low self-efficacy toward end-of-life care. The majority of students reported a positive disposition toward the provision of end-of-life care. The most important predictors of knowledge, attitudes, and self-efficacy were age, having attended a seminar/lecture on the issue, experiencing death while providing care, and having experienced a death in the family or close friends. Furthermore, elevated levels of knowledge were significantly associated with higher level of attitude (P < .001) about palliative care.
Extraskeletal Myxoid Chondrosarcoma
Authors: Brodsky Casey N. , Bucala Matthew D. , Abdulfatah Eman M. , Siegel Geoffrey W.
Published: February 2023

Objectives:

Extraskeletal myxoid chondrosarcoma (EMC) is an ultrarare soft tissue sarcoma, and a limited number of studies are published regarding its clinical course and efficacy of treatment. The goal of this retrospective case series is to explore patient characteristics, treatment approaches, and oncologic outcomes to help inform future EMC management.

Methods:

All patients with a diagnosis of EMC seen at the University of Michigan Sarcoma Center between 1998 and 2021 were identified. A chart review was performed to analyze demographics, tumor characteristics, treatments, and outcomes.

Results:

Forty-four patients with EMC were identified. The median follow-up was 49.8 months. The median age at diagnosis was 57 (range: 25 to 79), and 35 patients (80%) were male. Thirty-four patients (77%) had locoregional disease at diagnosis, and 26 patients (59%) ultimately developed metastatic disease. After locoregional curative-intent surgery, 15 patients had documented recurrence, of which 11 were metastatic (73%). Five-year overall survival was 79% for all patients, 86% for locoregional disease, and 58% for metastatic disease; for locoregional disease, 5-year disease-free and metastasis-free survival post-surgery were 43% and 53%, respectively; 1-year progression-free survival for metastatic disease from the start of first-line systemic therapy was 43%. Older age was the only factor statistically associated with improved prognosis, although perioperative radiotherapy, lower histologic grade, and negative margins also had directional associations with outcomes.

Conclusions:

The data in this patient series are generally consistent with published literature on EMC and demonstrate a high recurrence rate, high propensity for metastasis, and high rate of progression of metastatic disease on systemic therapy.