bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical behavior of recurrent hormone receptor–positive breast cancer by adjuvant endocrine therapy within the Breast International Group 1‐98 clinical trial
Authors: Leone Jose P. , Cole Bernard F. , Regan Meredith M. , Thürlimann Beat , Coates Alan S. , Rabaglio Manuela , Giobbie‐Hurder Anita , Gelber Richard D. , Ejlertsen Bent , Harvey Vernon J. , Neven Patrick , Láng Istvan , Bonnefoi Herve , Wardley Andrew , Goldhirsch Aron , Di Leo Angelo , Colleoni Marco , Vaz‐Luis Ines , Lin Nancy U.
Published: December 2020

Background

Endocrine therapy resistance is a major cause of distant recurrence (DR) in hormone receptor–positive breast cancer. This study evaluated differences in survival after DR in patients treated with different adjuvant endocrine therapy regimens in the Breast International Group (BIG) 1‐98 trial.

Methods

BIG 1‐98 compared 5 years of adjuvant treatment among 4 arms: tamoxifen (T), letrozole (L), tamoxifen followed by letrozole (TL), and letrozole followed by tamoxifen (LT). After a median follow‐up of 8.1 years, 911 of 8010 patients (T, 302; L, 285; TL, 170; and LT, 154) had DR as the site of first recurrence. Univariate and multivariate Cox analyses were performed to determine features associated with post‐DR survival.

Results

The median follow‐up time after DR was 59 months (interquartile range, 29‐88 months). Among all patients with DR, 38.1% were 65 years old or older at enrollment, 61.9% had tumors larger than 2 cm, and 69.7% were node positive. Neoadjuvant or adjuvant chemotherapy was administered to 35.6% of the patients. There was no difference in post‐DR survival by treatment arm (median survival, 20.8 months for T, 17.9 months for L, 17.3 months for TL, and 20.8 months for LT; P = .21). In multivariate analysis, older patients (hazard ratio [HR], 1.35; 95% confidence interval [CI], 1.15‐1.59) and patients with tumors larger than 2 cm (HR, 1.19; 95% CI, 1.00‐1.41), 4 or more positive nodes (HR, 1.31; 95% CI, 1.05‐1.64), progesterone receptor (PR)–negative tumors (HR, 1.25; 95% CI, 1.02‐1.52), or shorter disease‐free survival (DFS) had significantly worse post‐DR survival.

Conclusions

Treatment with adjuvant T, L, or their sequences was not associated with differences in survival after DR. Significant differences in survival were observed by age, primary tumor size, nodal and PR status, and DFS, and this suggests that traditional baseline high‐risk features remain prognostic in the metastatic setting.
Examining the dynamic nature of nonverbal communication between Black patients with cancer and their oncologists
Authors: Hamel Lauren M. , Moulder Robert , Harper Felicity W. K. , Penner Louis A. , Albrecht Terrance L. , Eggly Susan
Published: December 2020

Background

Although communication quality is associated with patient outcomes, racial disparities in communication exist, disproportionately burdening Black patients. However, most communication research focuses on verbal behaviors in predominantly White patient populations. We used a newly developed and theory‐guided network analysis that examines the dynamic interplay and behavioral convergence and divergence between Black patients with cancer and their oncologists during cancer treatment discussions.

Methods

We applied a nonverbal behavioral coding system to thin slices of video recordings of Black patients and their oncologists discussing treatment. We then estimated 3 networks: 1) a temporal network to determine whether a nonverbal behavior predicts another nonverbal behavior at the next time point in an interaction, and how much each nonverbal behavior influences other nonverbal behaviors and is influenced by other nonverbal behaviors; 2) a contemporaneous network to determine whether a nonverbal behavior co‐occurs with other nonverbal behaviors at the same time point in an interaction; and 3) a between‐dyads network to examine the covariation between nonverbal behaviors across all dyads.

Results

Black patients (n = 74) and their non‐Black physicians (n = 15) showed a mix of convergence and divergence in their nonverbal behaviors at the same points in time, from one time point to the next, and across dyads. Across analyses, convergence was most likely to occur when physicians matched their behaviors to their patients; especially with smiling, gaze, leaning, and laughter behaviors.

Conclusion

Our findings reveal patterns of modifiable behaviors that can potentially inform interventions to reduce disparities in clinical communication and, in turn, treatment and mortality disparities.
Commensal fungi and their cell‐wall β‐glucans direct differential responses in human intestinal epithelial cells
Authors: Cohen‐Kedar Sarit , Keizer Danielle , Schwartz Suzana , Rabinowitz Keren M. , Kaboub Kawsar , Shaham Barda Efrat , Sadot Eran , Wolff‐Bar Meirav , Shaltiel Tali , Dotan Iris
Published: December 2020

Intestinal epithelial cells (IECs) are the first to encounter luminal antigens and play an active role in intestinal immune responses. We previously reported that β‐glucans, major fungal cell‐wall glycans, induced chemokine secretion by IEC lines in a Dectin‐1‐ and Syk‐dependent manner. Here, we show that in contrast to β‐glucans, stimulation of IEC lines with Candida albicans and Saccharomyces cerevisiae did not induce secretion of any of the proinflammatory cytokines IL‐8, CCL2, CXCL1, and GM‐CSF. Commensal fungi and β‐glucans activated Syk and ERK in IEC lines. However, only β‐glucans activated p38, JNK, and the transcription factors NF‐κB p65 and c‐JUN, which were necessary for cytokine secretion. Furthermore, costimulation of IEC lines with β‐glucans and C. albicans yielded decreased cytokine secretion compared to stimulation with β‐glucans alone. Finally, ex vivo stimulation of human colonic mucosal explants with zymosan and C. albicans, leads to epithelial Syk and ERK phosphorylation, implying recognition of fungi and similar initial signaling pathways as in IEC lines.

Lack of cytokine secretion in response to commensal fungi may reflect IECs’ response to fungal glycans, other than β‐glucans, that contribute to mucosal tolerance. Skewed epithelial response to commensal fungi may impair homeostasis and contribute to intestinal inflammation.
Numerical simulation study on the mechanical behavior of shale core and reservoir rock mass
Authors: Li Yalong , Xiong Wei , Hu Zhiming , Duan Xianggang
Published: December 2020

After the hydraulic fracturing of the shale reservoir, the stress field changes during the mining process. The stress sensitivity of the reservoir affects its development capabilities. Moreover, the stress sensitivity of shale reservoirs obtained by various researchers using different experimental methods is not uniform. This study analyzes the physical background differences between reservoir rock mass and experimental core. In this study, we establish the “support structure model” of the reservoir and show that the reservoir rock body has a structural overall effect, such that the supporting effect of the surrounding rock on the overlying strata is very strong. At the same time, we also establish the transverse isotropic numerical model of the shale reservoir on the basis of the real physical background of the reservoir and the experimental physical core model on the basis of the real physical background of the core test. This study shows that the equivalent mechanical behavior of the core test in the holder is pure core compression without the support and pull of the whole rock mass structure. In the real reservoir, the reservoir rock mass has significant structural effect. The actual compression change of real reservoir mining is less than the pure compression displacement of the experimental test core. The core stress sensitivity of the conventional experimental test does not directly describe the true stress‐strain effect of the macroscopic reservoir rock mass as a structural whole. A laboratory stress‐sensitive test apparatus and method that is equivalent to the physical background of a real reservoir needs to be improved or designed.
Musical instrument training program improves verbal memory and neural efficiency in novice older adults
Authors: Guo Xia , Yamashita Masatoshi , Suzuki Maki , Ohsawa Chie , Asano Kohei , Abe Nobuhito , Soshi Takahiro , Sekiyama Kaoru
Published: December 2020

Previous studies indicate that musical instrument training may improve the cognitive function of older adults. However, little is known about the neural origins of training‐related improvement in cognitive function. Here, we assessed the effects of instrumental training program on cognitive functions and neural efficiency in musically naïve older adults (61–85 years old). Participants were assigned to either the intervention group, which received a 4‐month instrumental training program using keyboard harmonica, or a control group without any alternative training. Cognitive measurements and functional magnetic resonance imaging during visual working memory (VWM) task were administered before and after the intervention in both groups. Behavioral data revealed that the intervention group significantly improved memory performance on the test that measures verbal recall compared to the control group. Neuroimaging data revealed that brain activation in the right supplementary motor area, left precuneus, and bilateral posterior cingulate gyrus (PCgG) during the VWM task decreased after instrumental training only in the intervention group. Task‐related functional connectivity (FC) analysis revealed that the intervention group showed decreased FC between the right PCgG and left middle temporal gyrus, and between the left putamen and right superior temporal gyrus (lPu‐rSTG) during a VWM task after the intervention. Furthermore, a greater improvement in memory performance in the intervention group was associated with a larger reduction in lPu‐rSTG FC, which might be interpreted as improved neural efficiency. Our results indicate that the musical instrument training program may contribute to improvements in verbal memory and neural efficiency in novice older adults.
Hsa_circ_0102171 aggravates the progression of cervical cancer through targeting miR‐4465/CREBRF axis
Authors: Tang Xi , Wen Xiaomin , Li Zhouyu , Wen Danxia , Lin Ling , Liu Jinquan , Li Mingyi
Published: December 2020

Cervical cancer (CC) has caused numerous cancer‐related deaths in women. Recent years, circular RNAs have been reported as vital factors in CC tumorigenesis. Our current study focused on the role of hsa_circ_0102171 (called circ_0102171 subsequently) in CC. At first, we applied reverse transcription polymerase chain reaction to detect the expression of circ_0102171 in CC tissues and cells. Subsequently, we silenced circ_0102171 to conduct loss‐of‐function assays, including cell counting kit‐8 assay, 5‐ethynyl‐2'‐deoxyuridine staining, Transwell assay, and flow cytometry analysis. Interestingly, we discovered that circ_0102171 expressed at a high level in CC tissues and cells. Functionally, silencing circ_0102171 prohibited cell proliferation, migration and invasion, and strengthened cell apoptosis in CC in vitro. Mechanistic investigations revealed that circ_0102171 could act as a sponge for miR‐4465. Gain‐of‐function assays demonstrated that miR‐4465 hindered the growth and migration of CC cells. Moreover, circ_0102171 enhanced the level of CREB3 regulatory factor (CREBRF) which was the downstream target of miR‐4465. Rescue assays suggested that CREBRF and miR‐4465 could involve in circ_0102171‐mediated CC progression. Finally, in vivo data supported that silencing circ_0102171 hindered CC cell growth. In conclusion, circ_0102171 aggravates CC progression via targeting miR‐4465/CREBRF axis.
Repair bond strength and surface topography of resin‐ceramic and ceramic restorative blocks treated by laser and conventional surface treatments
Authors: Bayraktar Yusuf , Arslan Merve , Demirtag Zulfikar
Published: December 2020

This study intended to compare the repair bond strength of computer‐aided design/computer‐aided manufacturing (CAD/CAM) blocks consisting of resin and feldspathic ceramics following different surface treatments using the microtensile bond strength (μTBS) test. Ten specimens were prepared with 4 mm height for Vita Enamic (VE), Lava Ultimate (LU), Vita Mark II (VM), and thermocycled (10,000 cycle, 5–55°C). Each material was categorized into one of five subgroups according to following surface treatments: (a) bur grinding (BG), (b) hydrofluoric acid etching (HF), (c) neodymium‐doped yttrium aluminum garnet (Nd:YAG or NY), (d) erbium‐doped yttrium aluminum garnet (Er:YAG or EY), and (e) erbium, chromium‐doped yttrium, scandium, gallium, and garnet (Er,Cr:YSGG or ECY) laser conditioning. After surface treatment procedures, specimens were properly restored to 4 mm high with a micro‐hybrid composite resin. Bar specimens (1 × 1 × 8 mm) were obtained using a low‐speed cutting machine and then thermocycled (10,000 cycle, 5–55°C). The μTBS was tested at 1 mm/min crosshead speed, and failure modes were evaluated. Data were analyzed with two‐way ANOVA and post hoc Tukey tests. LU‐BG showed significantly higher μTBS (32.94 ± 5.80 MPa) compared to LU‐laser groups (p < .05). VE‐BG showed significantly higher μTBS (22.06 ± 4.26 MPa) compared to other VE groups (p < .05). Among the laser groups, the NY laser produced the lowest (p < .05) μTBS for LU (13.42 ± 3.44 MPa) and VE (2.27 ± 0.85 MPa), while EY showed the highest (p < .05). Laser‐treated VM groups were all prefailured. VM‐HF produced a higher μTBS (18.73 ± 3.75 MPa) than VM‐BG (5.05 ± 1.76 MPa) (p < .05).
Frontline Science: Estrogen-related receptor γ increases poly(I:C)-mediated type I IFN expression in mouse macrophages
Authors: Kim Ki-Sun , Kim Don-Kyu , Na Soon-Young , Jung Yoon Seok , Cho Sung Jin , Kim Jina , Lee In-Kyu , Kim Young-Hoon , Lee Chul-Ho , Jeong Won-Il , Jo Eun-Kyeong , Choi Hueng-Sik
Published: December 2020

Although type I IFNs (IFN-I) are important for the innate and adaptive immune responses to suppress viral replication, prolonged IFN-I signaling in macrophages suppresses the immune response. Nuclear receptor estrogen-related receptor γ (ERRγ) regulates the transcription of genes involved in endocrine and metabolic functions. However, the role of ERRγ in macrophage immune responses to viruses remains largely unknown. ERRγ expression was significantly induced in mouse bone marrow-derived macrophages (BMDMs) treated with polyinosinic-polycytidylic acid (poly(I:C)). Our results indicated that the induction of ERRγ expression by poly(I:C) is mediated through activation of the cytoplasmic dsRNA receptors, retinoic acid-inducible gene I and melanoma differentiation-associated protein 5. In BMDMs, overexpression of ERRγ significantly increased gene expression and secretion of the IFN-I genes, IFN-α and IFN-β, whereas abolition of ERRγ significantly attenuated poly(I:C)-mediated IFN-I secretion. Chromatin immunoprecipitation assays and mutation analyses of the IFN-I promoters revealed that ERRγ regulates the transcription of IFN-α and IFN-β by binding to a conserved ERR response element in each promoter region. Finally, GSK5182 significantly suppressed poly(I:C)-mediated induction of IFN-I gene expression and secretion in BMDMs. Taken together, these findings reveal a previously unrecognized role for ERRγ in the transcriptional control of innate and adaptive immune response to dsRNA virus replication.
Immune checkpoint markers and anti-CD20-mediated NK cell activation
Authors: Wang Zhaoming , Weiner George J
Published: December 2020

Anti-CD20 mAb is an effective therapy for most B-cell malignancies. Checkpoint blockade has been used to enhance T-cell-mediated antitumor response. Little is known about the biologic significance of immune checkpoints expressed by NK cells in anti-CD20-based therapy. To investigate the role of checkpoints in anti-CD20-mediated NK cell biology, Raji B-cell lymphoma cells, and PBMCs from normal donors were cocultured with rituximab (RTX), obinutuzumab (OBZ), or trastuzumab as a control mAb for between 20 h and 9 d. RTX and OBZ induced a dose-dependent NK cell up-regulation of T-cell immunoreceptor with Ig and ITIM domain (TIGIT) and T-cell immunoglobulin mucin-3 (TIM3), but not PD1, CTLA4, or LAG3. Resting CD56dim NK had higher TIGIT and TIM3 expression than resting CD56bright NK although TIGIT and TIM3 were up-regulated on both subsets. NK cells with the CD16 158VV single nucleotide polymorphism had greater TIM3 up-regulation than did NK from VF or FF donors. TIGIT+ and TIM3+ NK cells degranulated, produced cytokines, and expressed activation markers to a greater degree than did TIGIT– or TIM3– NK cells. Blockade of TIGIT, TIM3, or both had little impact on RTX-induced NK cell proliferation, degranulation, cytokine production, or activation. Taken together, TIGIT and TIM3 can serve as markers for anti-CD20-mediated NK cell activation, but may not serve well as targets for enhancing the anti-tumor activity of such therapy.
Evaluation of a deformable image registration quality assurance tool for head and neck cancer patients
Authors: Mee Molly , Stewart Kate , Lathouras Marika , Truong Helen , Hargrave Catriona
Published: December 2020

Introduction

A challenge in implementing deformable image registration (DIR) in radiation therapy planning is effectively communicating registration accuracy to the radiation oncologist. This study aimed to evaluate the MIM® quality assurance (QA) tool for rating DIR accuracy.

Methods

Retrospective DIR was performed on CT images for 35 head and neck cancer patients. The QA tool was used to rate DIR accuracy as good, fair or bad. Thirty registered patient images were assessed independently by three RTs and a further five patients assessed by five RTs. Ratings were evaluated by comparison of Hausdorff Distance (HD), Mean Distance to Agreement (MDA), Dice Similarity Coefficients (DSC) and Jacobian determinants for parotid and mandible subregions on the two CTs post‐DIR. Inter‐operator reliability was assessed using Krippendorff's alpha coefficient (KALPA). Rating time and volume measures for each rating were also calculated.

Results

Quantitative metrics calculated for most anatomical subregions reflected the expected trend by registration accuracy, with good obtaining the most ideal values on average (HD = 7.50 ± 3.18, MDA = 0.64 ± 0.47, DSC = 0.90 ± 0.07, Jacobian = 0.95 ± 0.06). Highest inter‐operator reliability was observed for good ratings and within the parotids (KALPA 0.66–0.93), whilst ratings varied the most in regions of dental artefact. Overall, average rating time was 33 minutes and the least commonly applied rating by volume was fair.

Conclusion

Results from qualitative and quantitative data, operator rating differences and rating time suggest highlighting only bad regions of DIR accuracy and implementing clinical guidelines and RT training for consistent and efficient use of the QA tool.
Efficacy of Photodynamic Anti‐Microbial Chemotherapy for Acanthamoeba Keratitis In Vivo
Authors: Dwia Pertiwi Yunialthy , Chikama Taiichiro , Sueoka Kentaro , Ko Ji‐Ae , Kiuchi Yoshiaki , Onodera Makoto , Sakaguchi Takemasa
Published: December 2020

Background and Objectives

Acanthamoeba keratitis is a sight‐threatening infectious disease that is difficult to treat. The aim of this study was to evaluate TONS504 (cationic chlorin derivative photosensitizer)‐mediated photodynamic antimicrobial chemotherapy (PACT) in vivo as a potential treatment for Acanthamoeba keratitis.

Study Design/Materials and Methods

Acanthamoeba keratitis was induced by soft contact lenses incubated with 1 × 105/ml Acanthamoeba castellanii, which were placed over debrided corneas with temporary tarsorrhaphy. Thirty‐eight male Japanese white rabbits were randomly divided into three groups (normal eye, no treatment, and treatment groups). TONS504 was administered as eye drops at 1 mg/ml, followed by light‐emitting diode irradiation after the establishment of keratitis at 7 days after infectious contact lens exposure. All animals were evaluated under a slit‐lamp microscope every 3 days for 6 days after the treatment. Clinical scores based on corneal epithelial defects detected by fluorescein staining, stromal opacity edema, and vascular infiltration into the cornea were determined. After 6 days, the eyes were enucleated for histopathological analysis.

Results

Clinical signs of infection in the treatment group were markedly reduced for up to 6 days after treatment. Histopathology showed a regular arrangement of stromal fibers and a small number of inflammatory cells in 58% of the corneas. However, 42% of corneas in the treatment group showed infiltrating neutrophils and irregular alignment of stromal collagen fibers.

Conclusions

Our TONS504‐PACT achieved complete recovery from keratitis in 58% of the rabbit models. Further studies are required to determine the conditions for the maximal effectiveness of our TONS504‐PACT for Acanthamoeba keratitis. Lasers Surg. Med. © 2020 Wiley Periodicals LLC
Corrosion behavior of T24, T92, VM12, and AISI 304 steels exposed to KCl–NaCl–K2SO4–Na2SO4 salt mixtures
Authors: Abu‐Warda Najib , López Antonio J. , Pedraza Fernando , Utrilla Maria V.
Published: December 2020

The corrosion mechanisms of T24, T92, VM12, and AISI 304 steels are studied under the influence of NaCl–KCl, NaCl–Na2SO4, and KCl–K2SO4 salt mixtures in a dry air atmosphere at 650°C for 15 days. NaCl–KCl was the most aggressive deposit and AISI 304 stainless steel exhibited the highest corrosion resistance. There was no relation between the Cr content of the ferritic steels and their corrosion resistance in NaCl–KCl. In contrast, the resistance of high‐Cr steels was better when exposed to NaCl–Na2SO4 and KCl–K2SO4. The high‐Cr and the low‐Cr steels were more susceptible to NaCl–Na2SO4 and to KCl–K2SO4, respectively.
Critical regularity criteria for Navier–Stokes equations in terms of one directional derivative of the velocity
Authors: Chen Hui , Fang Daoyuan , Zhang Ting
Published: December 2020

In this paper, we consider the 3D Navier–Stokes equations in the whole space. We investigate some new inequalities and a priori estimates to provide the critical regularity criteria in terms of one directional derivative of the velocity field, namely,
,
,
. Moreover, we extend the range of q while the solution is axisymmetric, that is, the axisymmetric solution u is regular in (0, T], if
,
,
Fasciculation analysis reveals a novel parameter that correlates with predicted survival in amyotrophic lateral sclerosis
Authors: Wannop Kate , Bashford James , Wickham Aidan , Iniesta Raquel , Drakakis Emmanuel , Boutelle Martyn , Mills Kerry , Shaw Chris
Published: December 2020

Introduction

Prognostic uncertainty in amyotrophic lateral sclerosis (ALS) confounds clinical management planning, patient counseling, and trial stratification. Fasciculations are an early clinical hallmark of disease and can be quantified noninvasively. Using an innovative analytical method, we correlated novel fasciculation parameters with a predictive survival model.

Methods

Using high‐density surface electromyography, we collected biceps recordings from ALS patients on their first research visit. By accessing an online survival prediction tool, we provided eight clinical and genetic parameters to estimate individual patient survival. Fasciculation analysis was performed using an automated algorithm (Surface Potential Quantification Engine), with a Cox proportional hazards model to calculate hazard ratios.

Results

The median predicted survival for 31 patients was 41 (interquartile range, 31.5‐57) months. Univariate hazard ratios were 1.09 (95% confidence interval [CI], 1.03‐1.16) for the rate of change of fasciculation frequency (RoCoFF) and 1.10 (95% CI, 1.01‐1.19) for the amplitude dispersion rate. Only the RoCoFF remained significant (P = .04) in a multivariate model.

Discussion

Noninvasive measurement of fasciculations at a single time‐point could enhance prognostic models in ALS, where higher RoCoFF values indicate shorter survival.
Seeding of Gastrostomy Tube Site in Patient With Squamous Cell Carcinoma of the Tongue: A Case Report
Authors: Wescott Bethaney , Seegmiller Sara , Mohamed Elfadil Osman , Schneckloth Jill , Hurt Ryan T. , Mundi Manpreet S.
Published: December 2020

Enteral nutrition (EN) is a widely used therapeutic tool to provide nutrition support for patients with various clinical conditions, including different types of cancer. Head and neck cancers, often complicated by dysphagia, are among leading indications for enteral feeding. Percutaneous endoscopic gastrostomy (PEG) and percutaneous endoscopic jejunostomy (PEJ) tubes are typically used to deliver EN. This article presents a case report of a young male with squamous cell carcinoma of the tongue. Unfortunately, he developed metastasis of his cancer at the right lateral side of the PEG placement site, requiring surgical resection of seeded growth at the PEG site. This rare complication can be challenging, as it requires a high index of suspicion to diagnose and can potentially limit nutrition support options. A number of theories have been proposed to explain seeding during PEG/PEJ placement, including direct repositioning of malignant cells during instrumentation. A specific placement technique has not been shown to be superior, as seeding was reported with all placement techniques. However, given the lack of statistically powerful studies to describe this entity, there are still gaps we need to explore to better understand seeding of feeding tubes and best practices around diagnosis and early treatment. EN continues to be an important part of caring for patients with cancer during active or palliative treatments. Understanding potential risks in the setting of cancer metastasis is beneficial to the patients and multidisciplinary teams involved. Early recognition of possible seeding of feeding tube sites is necessary to ensure subsequent timely surgical intervention.
Tracing the path of inhaled nitric oxide: Biological consequences of protein nitrosylation
Authors: Bhatia Vikram , Elnagary Lara , Dakshinamurti Shyamala
Published: December 2020

Nitric oxide (NO) is a comprehensive regulator of vascular and airway tone. Endogenous NO produced by nitric oxide synthases regulates multiple signaling cascades, including activation of soluble guanylate cyclase to generate cGMP, relaxing smooth muscle cells. Inhaled NO is an established therapy for pulmonary hypertension in neonates, and has been recently proposed for the treatment of hypoxic respiratory failure and acute respiratory distress syndrome due to COVID‐19. In this review, we summarize the effects of endogenous and exogenous NO on protein S‐nitrosylation, which is the selective and reversible covalent attachment of a nitrogen monoxide group to the thiol side chain of cysteine. This posttranslational modification targets specific cysteines based on the acid/base sequence of surrounding residues, with significant impacts on protein interactions and function. S‐nitrosothiol (SNO) formation is tightly compartmentalized and enzymatically controlled, but also propagated by nonenzymatic transnitrosylation of downstream protein targets. Redox‐based nitrosylation and denitrosylation pathways dynamically regulate the equilibrium of SNO‐proteins. We review the physiological roles of SNO proteins, including nitrosohemoglobin and autoregulation of blood flow through hypoxic vasodilation, and pathological effects of nitrosylation including inhibition of critical vasodilator enzymes; and discuss the intersection of NO source and dose with redox environment, in determining the effects of protein nitrosylation.
Influence of the Growth Substrate on the Internal Quantum Efficiency of AlGaN/AlN Multiple Quantum Wells Governed by Carrier Localization
Authors: Jacopin Gwénolé , Frankerl Christian , Tillner Nadine , Davies Matthew John , Rossbach Georg , Brandl Christian , Hoffmann Marc Patrick , Zeisel Roland , Hoffmann Axel , Lugauer Hans-Jürgen
Published: December 2020

The influence of the growth substrate on the internal quantum efficiency (IQE) of deep ultraviolet light‐emitting diodes is studied. Two nominally identical Al‐rich AlGaN/AlN multi‐quantum‐well (MQW) structures grown by metal–organic vapor phase epitaxy (MOVPE) on different substrates are investigated. The first MQW structure is grown on a native AlN substrate, whereas the second one is deposited on an AlN template on sapphire. By the combination of atomic force microscopy (AFM), photoluminescence (PL), and cathodoluminescence (CL) spectroscopy, it is demonstrated that the dislocation‐mediated spiral growth of MQWs on sapphire results in the more efficient localization of carriers. This effect helps to prevent nonradiative carrier recombination at point defects, improving the IQE of the structure.
On the metrological traceability and hierarchy of stable isotope reference materials aimed at realisation of the VPDB scale: Revision of the VPDBδ13C scale based on multipoint scale‐anchoring RMs
Authors: Assonov Sergey , Fajgelj Ales , Allison Colin , Gröning Manfred
Published: December 2020

Rationale

In recent years, the primary reference material (RM) for the VPDB scale, NBS19, has become unavailable, and the RM used for low‐end scale‐anchoring, LSVEC, was found unsuitable due a drift in theδ13C value. Given these problems, new RMs aimed at realising the VPDBδ13C scale with low uncertainty were produced. Establishing the consistency of the new RMs with the “old” RMs prompted our revision of the underlying principles of RM value assignments, and the VPDBδ13C scale realisation and its long‐term sustainability.

Methods

Analysis of major developments of the VPDB scale, a review of the contemporary requirements for RMs, and comparison with well‐established measurement scales have been performed, with the aim of revising the VPDBδ13C scale, principles of RM value assignments, and calibrator hierarchy. Requirements for scale‐anchoring RMs with low uncertainty and measures to establish the scale sustainability have been formulated.

Results

The revised scale realisation is based on multiple reference points, well‐defined calibration hierarchy and the use of well‐understood methods for value assignment. The realisation scheme includes the new primary RM IAEA‐603 and scale‐anchoring RMs IAEA‐610, IAEA‐611 and IAEA‐612, coveringδ13C from +2.46 to −36.7 ‰ VPDB, with uncertainties, including inhomogeneity and stability assessment, of less than 0.015 ‰. The values of these four RMs were assigned in a mutually consistent way; agreement between measurements made using this realisation with those made using the VPDB scale of 2006 has been demonstrated on NIST CO2RMs 8562–8564.

Conclusions

Multipoint‐anchoring of the VPDBδ13C scale provides several distinct “points” on the scale as means for cross‐measurements to check the stability and viability of RMs and detect drift of values, if any. This ensures that theδ13C scale is suitable for the most demanding applications, and provides options for developing further RMs with high accuracy inside a robust scale realisation scheme.
Ni‐Rich Layered Cathode Materials by a Mechanochemical Method for High‐Energy Lithium‐Ion Batteries
Authors: Tron Artur , Hong Meihua , Don Park Yeong , Kim Jiyong , Mun Junyoung
Published: December 2020

Ni‐rich cathode materials are attractive for use in high energy density lithium‐ion batteries due to low Co, high specific capacity and low cost; however, due to the poor cycling stability of materials with high Ni content of over 80 %, their large‐scale application in electric vehicles is limited. Furthermore, for industrial applications, it is important to simplify the synthetic procedures to reduce the manufacturing cost of the cathode material. A mechanochemical method is introduced for a combination of carbonate and hydroxide starting materials with Ni content of over 80, 85, and 90 %. These precursor materials are stable in air and are easy to use for the synthesis of LiNixCoyMnzO2 materials by solid state reaction. The crystalline structures and surface morphologies of the obtained mixed precursors and LiNixCoyMnzO2 powders are characterized using X‐ray diffraction analysis and field scanning electron microscopy with energy dispersive X‐Ray spectroscopy. The electrochemical performance is evaluated by repeat charge‐discharge cycling and measurement of the rate capability for various potential ranges from 3.0 to various high cut‐off potentials of 4.2, 4.3 and 4.4 V vs. Li/Li+. The results suggest that the whole process is very simple and similar to that used in the production of commercial LiNixCoyMnzO2, with no additional equipment needed in the application of this synthesis method for industrial purposes.
Microstructural Evolution during Homogenization and Hot Deformation for As‐Cast H13 Steel
Authors: Han Yahui , Li Changsheng , Ren Jinyi , Qiu Chunlin , Li En , Chen Shuaishuai
Published: December 2020

The hot compression experiments are accomplished to investigate the microstructural evolution of as‐cast H13 steel during homogenization treatment and hot deformation. At a certain homogenization temperature, the dynamic recrystallization (DRX) volume fraction increases with increasing strain and deformation temperature and decreasing strain rate. However, the DRX is also easy to proceed at a high strain rate of 5 s−1 due to the high shear stress. The recrystallization is inhibited in a dendrite segregation region. The residual dendrite segregation left after homogenization treatment will improve the recrystallization nucleation rate during the subsequent deformation. The recrystallization grains preferentially nucleate in the dendrite region, and the grain growth is inhibited by the dendrite segregation. The partial homogenization before deformation is beneficial to achieve the fine microstructure.
Astaxanthin as a new Raman probe for biosensing of specific subcellular lipidic structures: can we detect lipids in cells under resonance conditions?
Authors: Czamara Krzysztof , Adamczyk Adriana , Stojak Marta , Radwan Basseem , Baranska Malgorzata
Published: December 2020

Here we report a new Raman probe for cellular studies on lipids detection and distribution. It is (3S, 3'S)-astaxanthin (AXT), a natural xanthophyll of hydrophobic properties and high solubility in lipids. It contains a chromophore group, a long polyene chain of eleven conjugated C=C bonds including two in the terminal rings, absorbing light in the visible range that coincides with the excitation of lasers commonly used in Raman spectroscopy for studying of biological samples. Depending on the laser, resonance (excitation in the visible range) or pre-resonance (the near infrared range) Raman spectrum of astaxanthin is dominated by bands at ca. 1008, 1158, and 1520 cm−1that now can be also a marker of lipids distribution in the cells. We showed that AXT accumulates in lipidic structures of endothelial cells in time-dependent manner that provides possibility to visualize e.g. endoplasmic reticulum, as well as nuclear envelope. As a non-toxic reporter, it has a potential in the future studies on e.g. nucleus membranes damage in live cells in a very short measuring time.
Brückenvenenverletzungen bei Schütteltrauma
Authors: Wittschieber D. , Muggenthaler H. , Mall G. , Mentzel H.-J.
Published: December 2020

Das Schütteltrauma-Syndrom ist eine häufige Variante misshandlungsbedingter Kopfverletzungen bei Säuglingen und Kleinkindern und nach wie vor Gegenstand intensiver Forschungsbemühungen. Unter Verwendung verschiedener Bildgebungsmodalitäten wurden in den letzten Jahren mehrere Studien zur diagnostischen und forensischen Relevanz traumatisierter Brückenvenen durchgeführt. Im vorliegenden Beitrag werden der aktuelle Forschungsstand dargestellt und forensische Implikationen erörtert. Im Ergebnis der Metaanalyse der sieben gegenwärtig vorliegenden Untersuchungen ist festzustellen, dass Brückenvenenverletzungen bzw. Brückenvenenthrombosen häufig als rundlich und erweitert wirkende bzw. tubulär gestaltete Strukturen imponieren. Das „Tadpole“-Zeichen kann hierfür als ein wertvolles Hilfsmittel zu deren Identifizierung dienen. Insbesondere T2*/SWI-Sequenzen ermöglichen eine gute Detektierbarkeit dieser Läsionen und sollten bei Verdacht auf eine misshandlungsbedingte Kopfverletzung immer zusätzlich erstellt werden. Schlussfolgernd ist zu empfehlen, dass das Vorhandensein von radiologisch detektierbaren Brückenvenenverletzungen stets Anlass dazu geben sollte, auch nach weiteren Anzeichen einer Kindesmisshandlung zu suchen.
Retrospektiver Vergleich der roboterassistierten und der laparoskopischen Pyeloplastik an zwei Zentren
Authors: Griessner H. , Oberhammer L. , Pallauf M. , Oswald D. , Kunit T. , Colleselli D. , Merseburger A. , Kramer M. , Lusuardi L. , Mitterberger M.
Published: December 2020

Ziel

Wir verglichen in unserer retrospektiven Multicenterstudie die Ergebnisse der konventionell laparoskopischen Nierenbeckenplastik (L-NBP) mit denen der roboterassistierten Nierenbeckenplastik (R-NBP) nach Einführung des da Vinci X-Systems.

Methoden

Insgesamt wurden im definierten Zeitraum von Mai 2015 bis September 2019 76 Nierenbeckenplastiken an zwei unterschiedlichen Universitätskliniken durchgeführt. Für die Datenanalyse wurden 63 Patienten berücksichtigt, welche entweder eine L‑NBP (n = 27) oder eine R‑NBP (n = 36) nach Anderson und Hynse erhielten.

Ergebnisse

Das mediane Follow-up lag bei 22,5 (L-NBP) bzw. 12,7 (R-NBP) Monaten. Die statistische Analyse der Patientengruppen ergab bzgl. Alter, BMI, Geschlecht und betroffener Seite keinen statistischen Unterschied. Die Operationszeit war in der Gruppe der R‑NBP nicht statistisch signifikant kürzer (180 ± 72 vs. 159 ± 54 min, p = 0,194). Bezüglich postoperativer Major- bzw. Minor-Komplikationen nach Clavien-Dindo, Krankenhausaufenthaltsdauern (7,48 ± 2,86 vs. 6,33 ± 2,04 Tage) und Erfolgsrate ergab sich ebenso kein statistisch signifikanter Unterschied.

Schlussfolgerung

Unsere Daten zeigen keinen signifikanten Unterschied der beiden Gruppen bezogen auf die peri- und postoperativen Ergebnisse. Es konnte gezeigt werden, dass für den Patienten auch unmittelbar nach Implementierung eines robotischen Systems kein Nachteil entsteht.
Analysing the Operative Experience of Paediatric Surgical Trainees in Sub‐Saharan Africa Using a Web‐Based Logbook
Authors: Mooney Ciaran , Tierney Sean , O'Flynn Eric , Derbew Miliard , Borgstein Eric
Published: December 2020

Background

The expansion of local training programmes is crucial to address the shortages of specialist paediatric surgeons across Sub‐Saharan Africa. This study assesses whether the current training programme for paediatric surgery at the College of Surgeons of East, Central and Southern Africa (COSECSA) is exposing trainees to adequate numbers and types of surgical procedures, as defined by local and international guidelines.

Methods

Using data from the COSECSA web‐based logbook, we retrospectively analysed numbers and types of operations carried out by paediatric surgical trainees at each stage of training between 2015 and 2019, comparing results with indicative case numbers from regional (COSECSA) and international (Joint Commission on Surgical Training) guidelines.

Results

A total of 7,616 paediatric surgical operations were recorded by 15 trainees, at different stages of training, working across five countries in Sub‐Saharan Africa. Each trainee recorded a median number of 456 operations (range 56–1111), with operative experience increasing between the first and final year of training. The most commonly recorded operation was inguinal hernia (n = 1051, 13.8%). Trainees performed the majority (n = 5607, 73.6%) of operations recorded in the eLogbook themselves, assisting in the remainder. Trainees exceeded both local and international recommended case numbers for general surgical procedures, with little exposure to sub‐specialities.

Conclusions

Trainees obtain a wide experience in common and general paediatric surgical procedures, the number of which increases during training. Post‐certification may be required for those who wish to sub‐specialise. The data from the logbook are useful in identifying individuals who may require additional experience and centres which should be offering increased levels of supervised surgical exposure.
Fasted plasma asprosin concentrations are associated with menstrual cycle phase, oral contraceptive use and training status in healthy women
Authors: Leonard A. N. , Shill A. L. , Thackray A. E. , Stensel D. J. , Bishop Nicolette C.
Published: December 2020

Purpose

Asprosin, an orexigenic hormone that stimulates hepatic glucose release, is elevated in insulin resistance and associated with obesity. Plasma asprosin concentrations may also be related to female sex hormone levels; higher levels are reported in women with polycystic ovary syndrome (PCOS) but this may be related to peripheral insulin resistance also associated with PCOS. Clarification of female-specific factors influence on the plasma asprosin response is crucial for studies investigating asprosin. Therefore, this study determined the association of menstrual phase, oral contraceptive (OC) use (as a pharmacological influence on sex hormone levels) and training status (as a physiological influence on sex hormone levels) on plasma asprosin levels in pre-menopausal women.

Methods

Fasting plasma asprosin, 17β-estradiol (E2) and progesterone, were assessed in 32 healthy untrained and trained women with regular menstrual cycles (non-OC; n = 8 untrained, n = 6 trained) or using OC (n = 10 untrained, n = 8 trained) during early follicular, late follicular and mid-luteal menstrual phases (or the time-period equivalent for OC users).

Results

Asprosin was lower in OC (0.75 ± 0.38 ng mL−1) than non-OC users (1.00 ± 0.37 ng mL−1; p = 0.022). Across a cycle, asprosin was highest in the early follicular equivalent time-point in OC users (0.87 ± 0.37 ng mL−1) but highest in the mid-luteal phase in non-OC users (1.09 ± 0.40 ng mL−1). Asprosin concentrations varied more across a cycle in untrained than trained women, with higher concentrations in the early follicular phase compared to the late follicular and mid-luteal (training status-by-menstrual phase interaction p = 0.028).

Conclusion

These findings highlight the importance of considering OC use, menstrual cycle phase and to a lesser extent training status when investigating circulating asprosin concentrations in females.
A multi objective volleyball premier league algorithm for green scheduling identical parallel machines with splitting jobs
Authors: Salimifard Khodakaram , Li Jingpeng , Mohammadi Davood , Moghdani Reza
Published: December 2020

Parallel machine scheduling is one of the most common studied problems in recent years, however, this classic optimization problem has to achieve two conflicting objectives, i.e. minimizing the total tardiness and minimizing the total wastes, if the scheduling is done in the context of plastic injection industry where jobs are splitting and molds are important constraints. This paper proposes a mathematical model for scheduling parallel machines with splitting jobs and resource constraints. Two minimization objectives - the total tardiness and the number of waste - are considered, simultaneously. The obtained model is a bi-objective integer linear programming model that is shown to be of NP-hard class optimization problems. In this paper, a novel Multi-Objective Volleyball Premier League (MOVPL) algorithm is presented for solving the aforementioned problem. This algorithm uses the crowding distance concept used in NSGA-II as an extension of the Volleyball Premier League (VPL) that we recently introduced. Furthermore, the results are compared with six multi-objective metaheuristic algorithms of MOPSO, NSGA-II, MOGWO, MOALO, MOEA/D, and SPEA2. Using five standard metrics and ten test problems, the performance of the Pareto-based algorithms was investigated. The results demonstrate that in general, the proposed algorithm has supremacy than the other four algorithms.
Assessing the age specificity of infection fatality rates for COVID-19: systematic review, meta-analysis, and public policy implications
Authors: Levin Andrew T. , Hanage William P. , Owusu-Boaitey Nana , Cochran Kensington B. , Walsh Seamus P. , Meyerowitz-Katz Gideon
Published: December 2020

Determine age-specific infection fatality rates for COVID-19 to inform public health policies and communications that help protect vulnerable age groups. Studies of COVID-19 prevalence were collected by conducting an online search of published articles, preprints, and government reports that were publicly disseminated prior to 18 September 2020. The systematic review encompassed 113 studies, of which 27 studies (covering 34 geographical locations) satisfied the inclusion criteria and were included in the meta-analysis. Age-specific IFRs were computed using the prevalence data in conjunction with reported fatalities 4 weeks after the midpoint date of the study, reflecting typical lags in fatalities and reporting. Meta-regression procedures in Stata were used to analyze the infection fatality rate (IFR) by age. Our analysis finds a exponential relationship between age and IFR for COVID-19. The estimated age-specific IFR is very low for children and younger adults (e.g., 0.002% at age 10 and 0.01% at age 25) but increases progressively to 0.4% at age 55, 1.4% at age 65, 4.6% at age 75, and 15% at age 85. Moreover, our results indicate that about 90% of the variation in population IFR across geographical locations reflects differences in the age composition of the population and the extent to which relatively vulnerable age groups were exposed to the virus. These results indicate that COVID-19 is hazardous not only for the elderly but also for middle-aged adults, for whom the infection fatality rate is two orders of magnitude greater than the annualized risk of a fatal automobile accident and far more dangerous than seasonal influenza. Moreover, the overall IFR for COVID-19 should not be viewed as a fixed parameter but as intrinsically linked to the age-specific pattern of infections. Consequently, public health measures to mitigate infections in older adults could substantially decrease total deaths.
An evaluation of the molecular mode of action of trans-resveratrol in the Porphyromonas gingivalis lipopolysaccharide challenged neuronal cell model
Authors: Bahar Bojlul , Singhrao Sim K.
Published: December 2020

Porphyromonas gingivalis triggers a range of innate immune responses in the host that may contribute to the development of periodontitis and dementing diseases including Alzheimer’s disease (AD). This study aimed to assess the mode of action of trans-resveratrol in modulating the P. gingivalis lipopolysaccharide (PgLPS) induced metabolic inflammation in a neuronal cell model. Confluent IMR-32 neuroblastoma cells were treated with trans-resveratrol from Polygonum cuspidatum in the presence or absence of PgLPS. The abundance of messenger ribo-nucleic acid (mRNA) transcripts of a panel of 92 genes was quantitatively assessed through targeted transcriptome profiling technique and the biochemical pathways affected were identified through Ingenuity Pathway Analysis. Gene expression analysis revealed that trans-resveratrol down-regulated the mRNA of multiple gene markers including growth factors, transcription factors, kinases, trans-membrane receptors, cytokines and enzymes that were otherwise activated by PgLPS treatment of IMR-32 neuroblastoma cells. Pathway analysis demonstrated that the cellular oxidative stress caused by the activation of phosphoinositide-3-kinase/Akt1 (PI3K/Akt1) pathway that leads to the production of reactive oxygen species (ROS), chronic inflammatory response induced by the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) pathway and nutrient utilization pathways were favourably modulated by trans-resveratrol in the PgLPS challenged IMR-32 cells. This study demonstrates the potential of trans-resveratrol as a bioactive compound with multiple modes of intracellular action further supporting its therapeutic application in neuroinflammatory diseases.