bluuebunny/crossref_metadata_2025 huggingface dataset:
Pre-production results from ATLAS ITk Strip Sensors Quality Assurance Testchip
Authors: Allport P. , Bach E. , Basso M.J. , Chisholm A. , Cindro V. , Fadeyev V. , Fernández-Tejero J. , Fleta C. , George W. , Gonella L. , Hara K. , Hirose S. , Ishii T. , Klein C. , Knight T. , Koffas T. , Kopsalis I. , Kroll J. , Kuramochi K. , Kvasnicka J. , Latonova V. , Mandic I. , Mikestikova M. , Orr R.S. , Rossi E. , Saito K. , Sánchez S. , Soldevila U. , Staats E. , Ullán M. , Unno Y.
Published: November 2022

The production of strip sensors within the framework of the ATLAS Inner Tracker (ITk) development is a process which requires continuous evaluation during the full production period (about 4 years). Such an evaluation is divided into two different parts: Quality Control (QC), which focuses on the final product (the actual sensors) and tries to identify possible defects once the fabrication is completed, and Quality Assurance (QA), which aims to prevent deviations in the manufacturing process and uses specifically-designed test structures. The initial sensor pre-production consists of 5% (1041 sensors) of the total number of sensors expected during production. As part of pre-production, the collaboration has measured key parameters from miniature strip sensors (minis), monitor diodes (MD8), and the ATLAS Testchip, before and after irradiation. In this contribution we focus on the analysis of the results of the MD8 and the Testchip. All parameters have been obtained from the test structures (MD8, bias resistors, interdigitated structures, field oxide capacitors, coupling capacitors, punch-through protection structures and cross-bridge resistors) measured at the different test sites (KEK/Tsukuba, Birmingham, Toronto, Ljubljana, Valencia, Carleton, Prague, CNM-Barcelona). The results are compared to predefined pre- and post-irradiation specifications for each tested parameter.
Monte Carlo simulation method of polarization effects in Laser Compton Scattering on relativistic electrons
Authors: Filipescu Dan
Published: November 2022

Quasi-monochromatic, high energy and highly polarized γ-ray beam sources based on Compton scattering of laser photons (LCS) on relativistic electrons have developed for the last few decades as established instruments for nuclear physics studies. Following an extensive photoneutron experimental campaign at the LCS γ-ray beam line of the NewSUBARU synchrotron radiation facility at SPring8, Japan, a dedicated simulation code was developed for characterizing the incident γ-ray beams. The eliLaBr code is implemented using Geant4 and is available on the GitHub repository (github.com/dan-mihai-filipescu/eliLaBr). The present work describes step-by-step the Monte Carlo algorithm with focus on modeling the polarization properties of the scattered photon. The polarization is treated independently both in the Stokes parameters and in the polarization vector formalisms. An intervalidation between the two methods is given. Based on polarization state description requirements of different Geant4 physics classes, user recommendations are given on which of the two methods to be employed.

The spatial and energy distributions for the LCS γ-ray beam and its Stokes parameters are obtained for head-on laser — relativistic electron collisions, where several incident laser polarization states were considered: linear, unpolarized, circular and mixed linear and circular polarization. Results of previous investigations on the polarization of Compton scattered photons are reproduced.

The influence of variable incident angle between photon and electron beam was also investigated. We show that the degree of polarization transfer from the incident photon to the scattered photon increases with the collision angle, where head-on is considered 0°. However, as the polarization transfer is strongly influenced by the incident photon energy, we show that, for γ-ray sources based on Compton scattering of laser photons on relativistic electrons, the polarization degree of the incident photon is almost completely transferred to the scattered photon for any incident angle.
Multivariate Gaussian Random Fields over Generalized Product Spaces involving the Hypertorus
Authors: Bachoc François , Peron Ana , Porcu Emilio
Published: November 2022

The paper deals with multivariate Gaussian random fields defined over generalized product spaces that involve the hypertorus. The assumption of Gaussianity implies the finite dimensional distributions to be completely specified by the covariance functions, being in this case matrix valued mappings.

We start by considering the spectral representations that in turn allow for a characterization of such covariance functions. We then provide some methods for the construction of these matrix valued mappings. Finally, we consider strategies to evade radial symmetry (called isotropy in spatial statistics) and provide representation theorems for such a more general case.
Infinitesimal invariance of completely Random Measures for 2D Euler Equations
Authors: Grotto Francesco , Peccati Giovanni
Published: November 2022

We consider suitable weak solutions of 2-dimensional Euler equations on bounded domains, and show that the class of completely random measures is infinitesimally invariant for the dynamics. Space regularity of samples of these random fields falls outside of the well-posedness regime of the PDE under consideration, so it is necessary to resort to stochastic integrals with respect to the candidate invariant measure in order to give a definition of the dynamics. Our findings generalize and unify previous results on Gaussian stationary solutions of Euler equations and point vortices dynamics. We also discuss difficulties arising when attempting to produce a solution flow for Euler’s equations preserving independently scattered random measures.
Translanguaging Practices in Content-based Instruction in L2 Arabic
Authors: Oraby Ebtissam , Azaz Mahmoud
Published: November 2022

Using the tenets of translanguaging and with a focus on Arabic as a diglossic language, we examine the fluid and dynamic practices that transcend the boundaries between/among Standard Arabic, Arabic dialects, and English in content-based instruction in an advanced Arabic literature course. Using conversation analysis, we show how translingual practices in learner–learner and teacher–learner interactions and discussions utilize the available linguistic repertoires in the classroom discourse. These practices broke the priori established boundaries that set Standard Arabic as the target language. The use of Arabic dialects and English in the literature course promoted the negotiation of complex concepts, facilitated the engagement with and critical interpretation of literary texts, and enhanced the meaning-making process at large. The utilization of these translingual practices has maximized Arabic learners’ gains. The article theoretically enriches recent discussions about the role of available linguistic repertoires in the ideological divide between language and content courses in language programs. It also advances the position that pedagogical translanguaging destabilizes the status of standard varieties as the target in diglossic languages.
Surgical resection rates after neoadjuvant therapy for localized pancreatic ductal adenocarcinoma: meta-analysis
Authors: Brown Zachary J , Heh Victor , Labiner Hanna E , Brock Guy N , Ejaz Aslam , Dillhoff Mary , Tsung Allan , Pawlik Timothy M , Cloyd Jordan M
Published: November 2022

Background

Neoadjuvant therapy is increasingly being used before surgery for localized pancreatic cancer. Given the importance of completing multimodal therapy, the aim of this study was to characterize surgical resection rates after neoadjuvant therapy as well as the reasons for, and long-term prognostic impact of, not undergoing resection.

Methods

A systematic review and meta-analysis of prospective trials and high-quality retrospective studies since 2010 was performed to calculate pooled resection rates using a generalized random-effects model for potentially resectable, borderline resectable, and locally advanced pancreatic cancer. Median survival times were calculated using random-effects models for patients who did and did not undergo resection.

Results

In 125 studies that met the inclusion criteria, neoadjuvant therapy consisted of chemotherapy (36.8 per cent), chemoradiation (15.2 per cent), or chemotherapy and radiation (48.0 per cent). Among 11 713 patients, the pooled resection rates were 77.4 (95 per cent c.i. 71.3 to 82.5), 60.6 (54.8 to 66.1), and 22.2 (16.7 to 29.0) per cent for potentially resectable, borderline resectable, and locally advanced pancreatic cancer respectively. The most common reasons for not undergoing resection were distant progression for resectable and borderline resectable cancers, and local unresectability for locally advanced disease. Among 42 studies with survival data available, achieving surgical resection after neoadjuvant therapy was associated with improved survival for patients with potentially resectable (median 38.5 versus 13.3 months), borderline resectable (32.3 versus 13.9 months), and locally advanced (30.0 versus 14.6 months) pancreatic cancer (P < 0.001 for all).

Conclusion

Although rates of surgical resection after neoadjuvant therapy vary based on anatomical stage, surgery is associated with improved survival for all patients with localized pancreatic cancer. These pooled resection and survival rates may inform patient–provider decision-making and serve as important benchmarks for future prospective trials.
Mitochondrial haplogroups and cognitive progression in Parkinson’s disease
Authors: Liu Ganqiang , Ni Chunming , Zhan Jiamin , Li Weimin , Luo Junfeng , Liao Zhixiang , Locascio Joseph J , Xian Wenbiao , Chen Ling , Pei Zhong , Corvol Jean-Christophe , Maple-Grødem Jodi , Campbell Meghan C , Elbaz Alexis , Lesage Suzanne , Brice Alexis , Hung Albert Y , Schwarzschild Michael A , Hayes Michael T , Wills Anne-Marie , Ravina Bernard , Shoulson Ira , Taba Pille , Kõks Sulev , Beach Thomas G , Cormier-Dequaire Florence , Alves Guido , Tysnes Ole-Bjørn , Perlmutter Joel S , Heutink Peter , van Hilten Jacobus J , Barker Roger A , Williams-Gray Caroline H , Scherzer Clemens R ,   International Genetics of Parkinson Disease Progression (IGPP) Consortium, Liu Ganqiang , Valentino Rebecca R , Peng Jiajie , Liao Zhixiang , Locascio Joseph J , Corvol Jean-Christophe , Dong Xianjun , Maple-Grødem Jodi , Campbell Meghan C , Elbaz Alexis , Lesage Suzanne , Brice Alexis , Mangone Graziella , Growdon John H , Hung Albert Y , Schwarzchild Michael A , Hayes Michael T , Wills Anne-Marie , Herrington Todd M , Ravian Bernard , Shoulson Ira , Taba Pille , Kõks Sulev , Beach Thomas G , Cormier-Dequaire Florence , Alves Guido , Tysnes Ole-Bjørn , Perlmutter Joel S , Heutink Peter , van Hilten Jacobus J , Kasten Meike , Mollenhauer Brit , Trenkwalder Claudia , Klein Christine , Barker Roger A , Williams-Gray Caroline H , Marinus Johan , Scherzer Clemens R
Published: November 2022

Mitochondria are a culprit in the onset of Parkinson’s disease, but their role during disease progression is unclear. Here we used Cox proportional hazards models to exam the effect of variation in the mitochondrial genome on longitudinal cognitive and motor progression over time in 4064 patients with Parkinson’s disease. Mitochondrial macro-haplogroup was associated with reduced risk of cognitive disease progression in the discovery and replication population. In the combined analysis, patients with the super macro-haplogroup J, T, U# had a 41% lower risk of cognitive progression with P = 2.42 × 10−6 compared to those with macro-haplogroup H. Exploratory analysis indicated that the common mitochondrial DNA variant, m.2706A>G, was associated with slower cognitive decline with a hazard ratio of 0.68 (95% confidence interval 0.56–0.81) and P = 2.46 × 10−5. Mitochondrial haplogroups were not appreciably linked to motor progression. This initial genetic survival study of the mitochondrial genome suggests that mitochondrial haplogroups may be associated with the pace of cognitive progression in Parkinson’s disease over time.
Inflammation as a chemoprevention target in asbestos-induced malignant mesothelioma
Authors: Kadariya Yuwaraj , Sementino Eleonora , Shrestha Ujjawal , Gorman Greg , White Jonathan M , Ross Eric A , Clapper Margie L , Neamati Nouri , Miller Mark Steven , Testa Joseph R
Published: November 2022

Malignant mesothelioma (MM) is an incurable cancer of the serosal lining that is often caused by exposure to asbestos. Therefore, novel agents for the prevention and treatment of this disease are urgently needed. Asbestos induces the release of pro-inflammatory cytokines such as IL-1β and IL-6, which play a role in MM development. IL-6 is a component of the JAK-STAT3 pathway that contributes to inflammation-associated tumorigenesis. Glycoprotein 130 (gp130), the signal transducer of this signaling axis, is an attractive drug target because of its role in promoting neoplasia via the activation of downstream STAT3 signaling. The anticancer drug, SC144, inhibits the interaction of gp130 with the IL-6 receptor (IL6R), effectively blunting signaling from this inflammatory axis. To test whether the inflammation-related release of IL-6 plays a role in the formation of MM, we evaluated the ability of SC144 to inhibit asbestos-induced carcinogenesis in a mouse model. The ability of sulindac and anakinra, an IL6R antagonist/positive control, to inhibit MM formation in this model was tested in parallel. Asbestos-exposed Nf2+/−;Cdkn2a+/− mice treated with SC144, sulindac or anakinra showed significantly prolonged survival compared to asbestos-exposed vehicle-treated mice. STAT3 activity was markedly decreased in MM specimens from SC144-treated mice. Furthermore, SC144 inhibited STAT3 activation by IL-6 in cultured normal mesothelial cells, and in vitro treatment of MM cells with SC144 markedly decreased the expression of STAT3 target genes. The emerging availability of newer, more potent SC144 analogs showing improved pharmacokinetic properties holds promise for future trials, benefitting individuals at high risk of this disease.
Embedding research ethics into an international development programme: a case study of Evidence and Collaboration for Inclusive Development (ECID) in Nigeria
Authors: Bollaert Cathy , Aliyu Talatu , Cascant-Sempere Ma Josep
Published: November 2022

This case study engages critically with the challenges of integrating research into an international development programme. Recognizing knowledge production is currently dominated by western and colonial systems of meaning–making, the case study also explores how development research can be less extractive and how it can promote more equitable forms of knowledge production. This is explored and illustrated through the ethical challenges raised in the Evidence and Collaboration for Inclusive Development (ECID) programme. This was a four-year programme, funded by the UK Government, and delivered through a consortium of nine partners led by Christian Aid, and implemented by in-country partner organizations in Myanmar, Nigeria and Zimbabwe during 2019–2021.

The article begins by contextualizing the ECID programme within the wider research environment and within the Nigerian country context (which is given particular focus). It then explores the ethical challenges that emerged from the programme and how these were addressed. The paper concludes by offering an innovative model for shifting power in development research and doing research ethically with communities in a development programme. This requires thinking about how ethics in development research and practice can be reviewed in organizations, which typically do not have their own ethics review boards, and in ways which do not reproduce western hegemony in relation to whose knowledge and ethics count in research practice.
Sleeve lobectomy in patients with non-small-cell lung cancer: a report from the European Society of Thoracic Surgery database 2021
Authors: Gonzalez Michel , Chriqui Louis-Emmanuel , Décaluwé Herbert , Aigner Clemens , Rényi-Vámos Ferenc , Opitz Isabelle , Furák József , Szanto Zalan , Brunelli Alessandro , Falcoz Pierre-Emmanuel
Published: November 2022

OBJECTIVES

For centrally located lung tumours, sleeve lobectomy is preferred over pneumectomy. We report on the surgical practices and perioperative outcomes of sleeve resections based on data from the European Society of Thoracic Surgeons database.

METHODS

We retrieved data of patients undergoing sleeve lobectomy or bilobectomy from 2007 to 2021. We evaluated baseline characteristics, surgical approach, neoadjuvant treatments, morbidity and postoperative outcomes of open and video-assisted thoracoscopic surgery (VATS) procedures.

RESULTS

In total, 1652 patients (median age: 63 years; females/males: 446/1206) underwent sleeve lobectomy (n = 1536) or bilobectomy (n = 116) by open thoracotomy (n = 1491; 90.2%) or VATS (n = 161; 9.8%) with a thoracotomy conversion rate of 21.1% (n = 34); 398 (24.1%) patients received neoadjuvant treatment. Overall morbidity and 30-day mortality were 40.6% and 2.2%, respectively. Bronchial anastomotic complications occurred in 29 patients (1.8%) with conservative treatment in 6 cases (20.7%) and operative management in 23 (79.3%). On multivariable analysis, factors related to the elevated risk of cardiopulmonary complications were body mass index < 20 [odds ratio (OR): 2.26; P < 0.001] and bilobectomy (OR : 2.28, P < 0.001). Age <60 years (OR: 0.71, P = 0.013), female sex (OR: 0.54, P < 0.001) and VATS (0.64, P < 0.001) were associated with decreased risk. Neoadjuvant treatment was not associated with increased risks of cardiopulmonary complications (OR: 1.05; P = 0.664). Compared to open thoracotomy, VATS was associated with significantly decreased overall morbidity (30.4% vs 41.7%, P = 0.006) and length of stay (median: 5 days vs 8 days; P < 0.001).

CONCLUSIONS

Sleeve lobectomies can be safely performed after neoadjuvant treatment. The VATS approach fosters shorter length of stay and decreased morbidity.
Association of reproductive factors with cardiovascular disease risk in pre-menopausal women: nationwide population-based cohort study
Authors: Jeong Su-Min , Jeon Keun Hye , Jung Wonyoung , Yoo Jung Eun , Yoo Juhwan , Han Kyungdo , Kim Ju Youn , Lee Dong-Yun , Lee You-Bin , Shin Dong Wook
Published: November 2022

Background

Although the morbidity and mortality of cardiovascular diseases (CVD) are rising in young women, the risk factors of CVD among Korean pre-menopausal women have not been intensively investigated.

Aims

To determine how age at menarche and other female reproductive factors are associated with the risk of CVD in pre-menopausal women.

Methods and results

A total of 1 088 992 pre-menopausal women who participated in health screening in 2009 were included. The study outcomes were myocardial infarction (MI) and ischaemic stroke. Cox proportional hazards regression analysis was conducted with adjustment of traditional CVD risk factors and reproductive factors.

Results

Mean age was 43.8 ± 5.3 years (98.9%, < 55 years), 3.5% were current smokers, and 1.2% were heavy drinkers. During a mean follow-up of 8.3years [9 032 685.9 person-years (PY)], there were 10 876 CVD events (1.0 per 1000 PY).With later menarche, the risk of CVD increased; ≤12 years [adjusted hazard ratio (HR) 1.04, 95% confidence interval 0.93–1.16], 13 years (reference), 14 years (1.06, 0.98–1.14), 15 years (1.15, 1.07–1.24), 16 years (1.23, 1.14–1.34), and ≥17 years (1.33, 1.24–1.44). Compared with non-users, oral contraceptives (OC) users (≥1 year) had an increased risk of CVD (1.11, 1.01–1.22) (P for trend = 0.007).

Conclusions

Later menarche than the mean age at menarche (13 years old) and the use of OC (≥1 year) were associated with a higher risk of CVD, after adjusting for traditional cardiovascular risk factors. This study suggests that female reproductive factors could be unique risk factors for CVD in pre-menopausal women.
Mycobacterium tuberculosis sRNA MTS2823 regulates the growth of the multidrug-resistant strain in macrophages
Authors: Chen Zhen , Jiang Wei , Zhang Mengli , Yu Bo , Li Wei , Liu Jijun , Ai Fen
Published: November 2022

Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is a serious contagious disease. MTB-encoded small regulatory RNA (sRNA) MTS2823 was reported to be upregulated in the plasma of TB patients. Nevertheless, whether MTS2823 is implicated in MTB drug resistance is unclear. Human macrophage cell line THP-1 was infected with the drug-susceptible strain H37Rv or the multidrug-resistant (MDR) strain 8462. Colony-forming unit assay was implemented for evaluating intracellular growth of the MTB strains. Enzyme-linked immunosorbent assay was used for measurement of inflammatory cytokines. Real-time quantitative polymerase chain reaction was utilized to assess MTS2823 and recombinase A (recA) expression in strains 8462 and H37Rv. Nitric oxide (NO) production in the MDR strain-infected THP-1 cells was measured. In this study, MTS2823 was found to display a low level in the MDR strain. Overexpressing MTS2823 promoted intracellular growth of the MDR strain and inhibited inflammatory cytokine and NO production in infected THP-1 cells. RecA might be a target of MTS2823 in the MDR strain. Overall, MTB-encoded sRNA MTS2823 displays a low level and regulates the growth of the MDR strain in THP-1 cells by modulating recA.
Multi-glycomic analysis of spheroid glycocalyx differentiates 2- and 3-dimensional cell models
Authors: Zhou Qingwen , Alvarez Michael Russelle S , Solakyildirim Kemal , Tena Jennyfer , Serrano Luster Mae N , Lam Matthew , Nguyen Cynthia , Tobias Fernando , Hummon Amanda B , Nacario Ruel C , Lebrilla Carlito B
Published: November 2022

A multi-glycomic method for characterizing the glycocalyx was employed to identify the difference between 2-dimensional (2D) and 3-dimensional (3D) culture models with two human colorectal cancer cell lines, HCT116 and HT29. 3D cell cultures are considered more representative of cancer due to their ability to mimic the microenvironment found in tumors. For this reason, they have become an important tool in cancer research. Cell–cell interactions increase in 3D models compared to 2D, indeed significant glycomic changes were observed for each cell line. Analyses included the N-glycome, O-glycome, glycolipidome, glycoproteome, and proteome providing the most extensive characterization of the glycocalyx between 3D and 2D thus far. The different glycoconjugates were affected in different ways. In the N-glycome, the 3D cells increased in high-mannose glycosylation and in core fucosylation. Glycolipids increased in sialylation. Specific glycoproteins were found to increase in the 3D cell, elucidating the pathways that are affected between the two models. The results show large structural and biological changes between the 2 models suggesting that the 2 are indeed very different potentially affecting individual outcomes in the study of diseases.
A neurodevelopmental disorder associated with an activatingde novomissense variant inARF1
Authors: Ishida Morié , Otero María G , Freeman Christina , Sánchez-Lara Pedro A , Guardia Carlos M , Pierson Tyler Mark , Bonifacino Juan S
Published: November 2022

ADP-ribosylation factor 1 (ARF1) is a small GTPase that regulates membrane traffic at the Golgi apparatus and endosomes through recruitment of several coat proteins and lipid-modifying enzymes. Here, we report a pediatric patient with an ARF1-related disorder because of a monoallelic de novo missense variant (c.296 G > A; p.R99H) in the ARF1 gene, associated with developmental delay, hypotonia, intellectual disability and motor stereotypies. Neuroimaging revealed a hypoplastic corpus callosum and subcortical white matter abnormalities. Notably, this patient did not exhibit periventricular heterotopias previously observed in other patients with ARF1 variants (including p.R99H). Functional analysis of the R99H-ARF1 variant protein revealed that it was expressed at normal levels and properly localized to the Golgi apparatus; however, the expression of this variant caused swelling of the Golgi apparatus, increased the recruitment of coat proteins such as coat protein complex I, adaptor protein complex 1 and GGA3 and altered the morphology of recycling endosomes. In addition, we observed that the expression of R99H-ARF1 prevented dispersal of the Golgi apparatus by the ARF1-inhibitor brefeldin A. Finally, protein interaction analyses showed that R99H-ARF1 bound more tightly to the ARF1-effector GGA3 relative to wild-type ARF1. These properties were similar to those of the well-characterized constitutively active Q71L-ARF1 mutant, indicating that the pathogenetic mechanism of the R99H-ARF1 variant involves constitutive activation with resultant Golgi and endosomal alterations. The absence of periventricular nodular heterotopias in this R99H-ARF1 subject also indicates that this finding may not be a consistent phenotypic expression of all ARF1-related disorders.
Characterization of Classical Sheep Scrapie in White-tailed Deer after Experimental Oronasal Exposure
Authors: Greenlee Justin J , Moore S Jo , Cassmann Eric D , Lambert Zoe J , Kokemuller Robyn D , Smith Jodi D , Kunkle Robert A , Kong Qingzhong , Greenlee M Heather West
Published: November 2022

Background

Classic scrapie is a prion disease of sheep and goats that is associated with accumulation of abnormal prion protein (PrPSc) in the central nervous and lymphoid tissues. Chronic wasting disease (CWD) is the prion disease of cervids. This study was conducted to determine the susceptibility of white-tailed deer (WTD) to the classic scrapie agent.

Methods

We inoculated WTD (n = 5) by means of a concurrent oral/intranasal exposure with the classic scrapie agent from sheep or oronasally with the classic scrapie agent from goats (n = 6).

Results

All deer exposed to the agent of classic scrapie from sheep accumulated PrPSc. PrPSc was detected in lymphoid tissues at preclinical time points, and necropsies in deer 28 months after inoculation showed clinical signs, spongiform lesions, and widespread PrPSc in neural and lymphoid tissues. Western blots on samples from the brainstem, cerebellum, and lymph nodes of scrapie-infected WTD have a molecular profile similar to CWD and distinct from samples from the cerebral cortex, retina, or the original classic scrapie inoculum. There was no evidence of PrPSc in any of the WTD inoculated with classic scrapie prions from goats.

Conclusions

WTD are susceptible to the agent of classic scrapie from sheep, and differentiation from CWD may be difficult.
Validation of a New Salt-Assisted HS-GC–FID Method for the Determination of Ethanol in the Vitreous Humor
Authors: Musile Giacomo , Pigaiani Nicola , Pasetto Emma , Ballotari Marco , Tagliaro Franco , Bortolotti Federica
Published: November 2022

Headspace gas chromatography with a flame ionization detector (HS-GC–FID) is a well-established approach for determining blood alcohol concentration, including in cadaveric specimens. Although the integrity of blood specimens can be adequately guaranteed after the sampling, the quantification of ethanol in cadaveric blood can be affected by postmortem fermentative phenomena occurring between the time since death and the sampling of biofluids. The vitreous humor is less affected by putrefactive phenomena allowing compound determination and its use as an alternative biological matrix. The present work aimed to develop and validate a method using the salting-out effect and based on HS-GC–FID for the determination of ethanol in the vitreous humor. The reported analytical method is based on a simple vitreous humor pre-treatment consisting of a dilution (1:9) with a solution of 2.5 mol/L K2CO3 and 0.0012 mol/L tert-butanol (internal standard). After 1 min of incubation, part of the specimen evaporated in the headspace (2,000 µL) is injected into the chromatographic system and analyzed in isothermal mode (40°C), with a chromatographic time of 1.6 min. The method was validated in terms of selectivity, the lowest limit of detection, intraday and total imprecision, and trueness (bias). The determination of ethanol in the vitreous humor and blood was carried out in 75 cases. The correlation between the two matrices was confirmed in 61 cases. However, 14 vitreous humor specimens showed lower ethanol concentrations, and in the related blood specimens, it was possible to identify the signal of n-propanol, a typical product of postmortem microbial fermentation, that justifies the excess of ethanol in the blood specimens.
Observational constraints on varying fundamental constants in a minimal CPC model
Authors: Cuzinatto R R , Holanda R F L , Pereira S H
Published: November 2022

A minimal model based on the Co-varying Physical Couplings (CPC) framework for gravity is proposed. The CPC framework is based on the assumptions of a metric-compatible four-dimensional Riemannian manifold, where a covariantly conserved stress-energy tensor acts as source of the field equations, which are formally the same as Einstein field equations, but where the couplings {G, c, Λ} are allowed to vary simultaneously. The minimal CPC model takes Λ as a genuine constant while c and G vary in an entangled way that is consistent with Bianchi identity and the aforementioned assumptions. The model is constrained using the most recent galaxy cluster gas mass fraction observational data. Our result indicates that the functions c(z) and G (z) = G0 (c/c0)4 are compatible with constant couplings for the two different parametrizations of c = c(z) adopted here.
Subcellular redox responses reveal different Cu-dependent antioxidant defenses between mitochondria and cytosol
Authors: Zhang Yuteng , Wen Meng-Hsuan , Qin Guoting , Cai Chengzhi , Chen Tai-Yen
Published: November 2022

Excess intracellular Cu perturbs cellular redox balance and thus causes diseases. However, the relationship between cellular redox status and Cu homeostasis and how such an interplay is coordinated within cellular compartments has not yet been well established. Using combined approaches of organelle-specific redox sensor Grx1-roGFP2 and non-targeted proteomics, we investigate the real-time Cu-dependent antioxidant defenses of mitochondria and cytosol in live HEK293 cells. The Cu-dependent real-time imaging experiments show that CuCl2 treatment results in increased oxidative stress in both cytosol and mitochondria. In contrast, subsequent excess Cu removal by bathocuproine sulfonate, a Cu chelating reagent, lowers oxidative stress in mitochondria but causes even higher oxidative stress in the cytosol. The proteomic data reveal that several mitochondrial proteins, but not cytosolic ones, undergo significant abundance change under Cu treatments. The proteomic analysis also shows that proteins with significant changes are related to mitochondrial oxidative phosphorylation and glutathione synthesis. The differences in redox behaviors and protein profiles in different cellular compartments reveal distinct mitochondrial and cytosolic response mechanisms upon Cu-induced oxidative stress. These findings provide insights into how redox and Cu homeostasis interplay by modulating specific protein expressions at the subcellular levels, shedding light on understanding the effects of Cu-induced redox misregulation on the diseases.
Time for a drought experiment: Do you know your plants’ water status?
Authors: Juenger Thomas E , Verslues Paul E
Published: November 2022

Drought stress is an increasing concern because of climate change and increasing demands on water for agriculture. There are still many unknowns about how plants sense and respond to water limitation, including which genes and cellular mechanisms are impactful for ecology and crop improvement in drought-prone environments. A better understanding of plant drought resistance will require integration of several research disciplines. A common set of parameters to describe plant water status and quantify drought severity can enhance data interpretation and research integration across the research disciplines involved in understanding drought resistance and would be especially useful in integrating the flood of genomic data being generated in drought studies. Water potential (ψw) is a physical measure of the free energy status of water that, along with related physiological measurements, allows unambiguous description of plant water status that can apply across various soil types and environmental conditions. ψw and related physiological parameters can be measured with relatively modest investment in equipment and effort. Thus, we propose that increased use of ψw as a fundamental descriptor of plant water status can enhance the insight gained from many drought-related experiments and facilitate data integration and sharing across laboratories and research disciplines.
High-Resolution Melting-Based Marker Development for Wheat Leaf Rust Resistance Gene Lr34
Authors: Kaur Shivreet , Pennington Taylor , Conley Emily J. , Green Andrew , Kolmer James , Anderson James , Gupta Rajeev , Gill Upinder
Published: November 2022

Deploying adult plant resistance (APR) against rust diseases is an important breeding objective of most wheat-breeding programs. The gene Lr34 is an effective and widely deployed broad-spectrum APR gene in wheat against leaf rust fungus Puccinia triticina. Various molecular markers have been developed for Lr34, but they either require post-PCR handling processes or are not economical. Herein, we developed a high-resolution melting (HRM)-based diagnostic assay for Lr34 based on a 3-bp ‘TTC’ deletion in exon 11 of the resistant allele. The susceptible cultivar Thatcher (Tc) and the near-isogenic Thatcher line (RL6058) with Lr34 yielded distinct melting profiles and were differentiated with high reproducibility. For further validation, all three copies of Lr34 were cloned in plasmid vectors, and HRM analysis using individual and combination (equimolar mixture of three copies) homoeologs yielded distinct melting profiles. An additional layer of genotyping was provided by a LunaProbe assay. The allele-specific probes successfully distinguished the homoeologs but not Tc and RL6058. Furthermore, the practical deployment of the HRM assay was tested by running the marker on a set of breeding lines. When compared with a kompetitive allele-specific PCR (KASP) Lr34 assay, the HRM assay had similar genotyping results and was able to accurately differentiate the resistant and susceptible breeding lines. However, our HRM assay was unable to detect the heterozygote. To our knowledge, this is the first report of an HRM assay for genotyping a wheat rust resistance gene.
Assessing Clinically Significant Cognitive Impairment Using the NIH Toolbox in Individuals with Co-occurring Serious Mental Illness and Alcohol Use Disorder
Authors: Jett Julianne D. , Kordas Gordon , Parent Sara , Keshtkar Mohammad , Shin Rachel , King Paige , McPherson Sterling M. , Ries Richard , Roll John M. , McDonell Michael G. , Chaytor Naomi
Published: November 2022

Objective

Serious mental illnesses (SMI) and alcohol use disorder (AUD) co-occurrence (SMI-AUD) is common, yet little is known about the prevalence and risk factors of cognitive impairment for this population. We used the National Institutes of Health (NIH) Toolbox to identify clinically significant cognitive impairment (CSCI), describe the cognitive profile, and investigate whether psychiatric and AUD severity measures are associated with CSCI in individuals with SMI-AUD.

Methods

CSCI was defined as 2 or more fully corrected fluid subtest T scores below a set threshold based on an individual’s crystalized composite score. Psychiatric severity measures included the Structured Clinical Interview for DSM-V (SCID-5) for SMI diagnosis and the Positive and Negative Syndrome Scale. AUD severity measures included the SCID-5 for AUD symptom severity score, years of alcohol use, and urine ethyl glucuronide levels. A multivariable logistic regression was used to investigate the adjusted effects of each variable on the probability of CSCI.

Results

Forty-one percent (N = 55/135) of our sample had CSCI compared with the base rate of 15% from the NIH Toolbox normative sample. Subtests measuring executive function most frequently contributed to meeting criteria for CSCI (Flanker and Dimensional Change Card Sort). A history of head injury (P = 0.033), increased AUD symptom severity score (P = 0.007) and increased negative symptom severity score (P = 0.027) were associated with CSCI.

Conclusions

Cognition should be considered in the treatment of people with SMI-AUD, particularly in those with history of brain injury, higher AUD symptom severity, and/or negative symptom severity.
Prediction Model for Job Retention According to the Type of Return to Work Among Industrially Injured Workers in Korea
Authors: Bae Suk Won , Won Jong-Uk , Park Wha Me
Published: November 2022

Objectives

This study aimed to investigate how the type of return to work after an industrial accident affects job retention.

Methods

Using data from the panel study of workers' compensation insurance first-third, and hazard ratios (HRs) and 95% confidence intervals were calculated for workers leaving their jobs.

Results

The HR leaving their jobs were higher in the “reemployed” compared with that in the “returned to original work,” with HR of 2.69 (2.33–3.10). According workers' status, the HRs leaving their jobs were higher among the “reemployed” than among those who “returned to original work.” Regular and daily workers' HRs were 1.70 (1.37–2.11) and 3.55 (2.96–4.26), respectively.

Conclusions

The findings suggest that to increase job retention rate, protection policies for reemployed workers or support for employers who hire reemployed workers should be considered.
Identification of Risk Factors of Recurrence Among Patients With Vulvar Paget Disease Treated With Conservative Surgery
Authors: Pergialiotis Vasilios , Christodoulou Theano , Ferousis Loukas , Thomakos Nikolaos , Rodolakis Alexandros , Haidopoulos Dimitrios
Published: November 2022

Objectives

Vulvar Paget disease (VPD) is a benign disease with high recurrence rates. Standard treatment involves conservative surgery with wide local excision of the lesion. The purpose of the present study is to identify factors that increase the risk of relapse.

Materials and Methods

We conducted a retrospective study and included patients treated with conservative surgery for noninvasive VPD. Cox regression analysis was carried out to assess the independent effect of age, presence of positive margins, tumor size greater than 4 cm, bilateral lesions, and compositive morbidity and pathology on recurrence free survival. Post hoc power analysis was performed with the G-power tool using an α error of 0.05.

Results

Overall, 39 patients were included with a median age of 70 years (46–85 years). Of those, 19 patients relapsed within a median duration of 30.5 months (5–132 months). Twelve patients (63%) experienced at least a second relapse. The presence of composite comorbidity significantly affected the interval to recurrence (30.09 vs 71.80 months, p = .032). Univariate Cox regression analysis revealed that the presence of composite pathology features was indicative of a higher risk of recurrence (hazard ratio = −3.71, p = .024). The sample size did not allow for adequate power for this latter finding. Microscopically involved tumor margins and tumor size greater than 4 cm did not predict patients at risk of experiencing relapsing disease.

Conclusions

Patients with noninvasive VPD experience high relapse rates. The presence of concurrent benign vulvar pathology may increase these rates, although larger sample sizes are needed to ascertain our findings.
Psychosexual Impact on a Sample of Hispanic Women With Human Papillomavirus
Authors: Colón-Valentín Janyfel , Esteban Caleb , Frontera-Hernández Mariana , Gutiérrez del Arroyo-Lebrón Verónica , Rivera-Casul Giuliana , Hoyos Viviana , Romaguera Josefina
Published: November 2022

Objectives

Our study investigates the psychosexual impact of human papillomavirus (HPV) diagnosis and its associated conditions on Hispanic women living in Puerto Rico.

Materials and Methods

A cross-sectional quantitative study was conducted on 205 women between 21 and 65 years old who received services at the Gynecology Clinics of the Medical Sciences Campus from April 2019 to December 2019. After obtaining approval from the institutional review board (March 27, 2019) and the informed consent of participants, participants completed a sociodemographic questionnaire and 4 psychological symptomatology-based questionnaires that measured levels of anxiety, depression, sexual satisfaction, and self-esteem.

Results

Of the participants, 48.8% had a known diagnosis of HPV (n = 100) compared with 51.2% without a known HPV diagnosis (n = 105). A Mann-Whitney U test analysis for independent samples was used, which showed that patients with known HPV diagnoses had higher reported levels of anxiety in the Generalized Anxiety Disorder Scale with a statistical significance of 0.03, as compared with patients without a known HPV diagnosis. There was no significant difference in reported levels of depressive symptoms, self-esteem, or sexual satisfaction between the groups.

Conclusions

Our findings show that in this group of Hispanic women living in Puerto Rico, being diagnosed with HPV and its associated conditions can be associated with higher anxiety symptoms. Further studies are warranted in this population to help improve their health outcomes and access to proper primary and preventive care.
Relationship between 18F-fluorodeoxyglucose PET/computed tomography metabolic parameters and clinicopathology in endometrial cancer
Authors: Yao Xinchao , Tan Xiaoyue , Zhang Hongna , Yuan Hui , Zeng Baozhen , He Li , Jiang Lei
Published: November 2022

Objective

Endometrial cancer (EC) is the most common invasive gynecological malignancy. This study aimed to retrospectively analyze the relationship between 18F-fluorodeoxyglucose (18F-FDG) PET/computed tomography (CT) parameters and clinicopathological factors in EC patients, and assess whether 18F-FDG PET/CT can be applied for predicting the expressed status of histologic molecular markers.

Methods

Pretreatment clinicopathological characteristics and 18F-FDG PET/CT parameters of maximum standard uptake value (SUVmax), metabolic tumor volume and total lesion glycolysis of primary lesion (MTV-P and TLG-P), and combination of primary lesion and metastases (MTV-C and TLG-C) were retrospectively reviewed in 101 patients with EC.

Results

The median age of these 101 patients was 55 years (range, 35–85 years), and 95 patients (94.1%) presented with abnormal vaginal bleeding, 26 patients (25.7%) with elevated serum cancer antigen 125 (CA-125) and 46 patients (45.5%) with increased human epididymis protein 4 (HE4). Sixty-nine cases were at International Federation of Gynecology and Obstetrics (FIGO) stage I, eight at stage II, 20 at stage III, and four at stage IV. FDG uptake was avid in all cases, and the median SUVmax, MTV-P, TLG-P, MTV-C, and TLG-C were 12.9 (range, 2.8–34.2), 8.1 (range, 0.9–547.8), 52.2 (range, 2.5–4420.6), 8.2 (range, 0.9–790.3), and 58.4 (range, 2.5–6972.2), respectively. Estrogen receptor (ER) and progesterone receptor (PR) positive expressions were in 93.1% (94/101) and 90.1% (91/101) patients, respectively. The median Ki-67 index of 101 cases was 40% (range, 0–95%). P53 pattern was tested in 89 patients and 24 cases were mutant type (27.0%). Mesenchymal-epithelial transition factor (c-Met) expression was investigated in 86 patients, and the positivity was in 36 patients (41.9%). Higher PET/CT metabolic parameters were observed in patients with elevated CA-125 and HE4, advanced FIGO stage and higher Ki-67 index (P < 0.05), but had no association with ER/PR expression, P53 pattern, and c-Met expression (P > 0.05).

Conclusion

FDG uptake in EC was associated with serum CA-125 and HE4, FIGO stage, and Ki-67 index, but no correlations were found between glucose metabolism and ER/PR, P53, and c-Met.
Antibiotic administration within 1 hour for open lower extremity fractures is not associated with decreased risk of infection
Authors: Grigorian Areg , Schellenberg Morgan , Inaba Kenji , Martin Matthew , Matsushima Kazuhide , Lekawa Michael , Nahmias Jeffry
Published: November 2022

BACKGROUND

Open fractures have a high risk of infection with limited data correlating timing of prophylactic antibiotic administration and rate of subsequent infection. The Trauma Quality Improvement Program has established a standard of antibiotic administration within 1 hour of arrival, but there is a lack of adequately powered studies validating this quality metric. We hypothesize that open femur and/or tibia fracture patients undergoing orthopedic surgery have a decreased risk of infectious complications (osteomyelitis, deep and superficial surgical site infection) if antibiotics are administered within 1 hour of presentation compared with administration after 1 hour.

METHODS

The 2019 Trauma Quality Improvement Program was queried for adults with isolated (Abbreviated Injury Scale <1 for the head/face/spine/chest/abdomen/upper extremity) open femur and/or tibia fractures undergoing orthopedic surgery. Transfer patients were excluded. Patients receiving early antibiotics (EA) within 1 hour were compared with patients receiving delayed antibiotics (DA) greater than 1 hour from arrival.

RESULTS

Of 3,367 patients identified, 2,400 (70.4%) received EA. Patients receiving EA had a higher rate of infections compared with DA (1.1% vs. 0.2%, p = 0.011). After adjusting for age, comorbidities, injury severity, nerve/vascular trauma to the lower extremity, washout of the femur/tibia performed in <6 hours, blood transfusion, and admission vitals, patients in the EA group had a similar associated risk of surgical site infection/osteomyelitis compared with the DA cohort (p = 0.087). These results remained in subset analyses of patients with only femur, only tibia, and combined femur/tibia open fractures (all p > 0.05).

CONCLUSION

In this large national analysis, approximately 70% of isolated open femur or tibia fracture patients undergoing surgery received antibiotics within 1 hour. After adjusting for known risk factors of infection, there was no association between timing of antibiotic administration and infection. Reconsideration of the quality metric of antibiotic administration within 1 hour for open fractures appears warranted.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level IV.
Thrombotic storm in coronavirus disease 2019: from underlying mechanisms to its management
Authors: Zebardast Arghavan , Latifi Tayebeh , Shabani Mehdi , Hasanzadeh Ali , Danesh Manizheh , Babazadeh Sara , Sadeghi Farzin
Published: November 2022

Introduction. Coronavirus disease 2019 (COVID-19) identified in December 2019 in Wuhan, China, is associated with high mortality rates worldwide.

Hypothesis/Gap Statement. Thrombotic problems, such as coagulopathy, are common in COVID-19 patients. Despite anticoagulation, thrombosis is more common in patients in the intensive care unit and patients with more severe disease. Although the exact mechanisms of coagulopathy in COVID-19 patients are still unclear, studies showed that overactivation of the renin-angiotensin system (RAS), cytokine storm, endothelial damage, formation of neutrophil extracellular traps (NETs), and also extracellular vesicles (EVs) in response to COVID-19 induced inflammation can lead to systemic coagulation and thrombosis.

Aim. The management of COVID-19 patients requires the use of basic and readily available laboratory markers, both on admission and during hospitalization. Because it is critical to understand the pathophysiology of COVID-19 induced coagulopathy and treatment strategies, in this review we attempt to explain the underlying mechanism of COVID-19 coagulopathy, its diagnosis, and the associated successful treatment strategies.

Conclusion. The exact mechanisms behind COVID-19-related coagulopathy are still unclear, but several studies revealed some mechanisms. More research is needed to determine the best anticoagulant regimen and to study other therapeutic options.