bluuebunny/crossref_metadata_2025 huggingface dataset:
Polycarbazole Electropolymerization Materials with Excellent Electrochromic Performance Based on Phenothiazine/Phenoxazine Group
Authors: Huang Qidi , Chen Jianai , Shao Xiongchao , Dong Yujie , Li Weijun , Zhang Cheng
Published: July 2022

Electrochromic small molecules suffer from the difficult film processibility and serious dissolvability at their oxidation state, which greatly limit their applications in electrochromic areas. Here, well‐defined electrochemical polymer structures, pCZ‐FSQ and pCZ‐FEQ, are obtained by taking advantage of the unique electrochemical dimerization of carbazole, and low redox‐potential phenothiazine and phenoxazine groups are introduced as an electrochromic color‐changing unit with the interruption of conjugation between them via an alkyl chain linkage. The obtained polymer films pCZ‐FSQ and pCZ‐FEQ are composed of the independent dimeric carbazole and organic small molecule units. Finally, they exhibit outstanding electrochromic properties with optical contrast of more than 50%, switching time of less than 1 s, excellent stability (over 500 cycles of optical stability), and ultrahigh coloration efficiency (276 cm2C−1for pCZ‐FSQ,384 cm2C−1for pCZ‐FEQ). This is thought to be greatly attributed to the well‐defined electrochemical polymer structures with dual electrochromic color‐changing properties of both phenothiazine/phenoxazine and dimeric carbazole. This can also provide some implications for the future in‐depth study of small molecule electrochromism and the solution to the problem of difficult processing of small molecules.
Improved p‐version finite element matrix conditioning using semi‐orthogonal modal approximation functions
Authors: Winterscheidt Daniel
Published: July 2022

Recursive equations for the efficient computation of nearly orthogonal, C0 continuous p‐version approximation functions (“max‐orthogonal”) are developed in one dimension and used to construct hexagonal (“brick”) element approximation functions. A modification to the functions is presented to simplify adaptive p‐refinement, resulting in “semi‐orthogonal” approximation functions. These functions are found to produce Laplace equation stiffness matrices, as well as mass matrices, with substantially lower condition numbers compared to standard Legendre‐based modal functions. Sample problems are presented using a conjugate gradient matrix solver to compare the matrix solution computation times using max‐orthogonal, semi‐orthogonal, and standard modal functions. Automatic adaptive polynomial refinement is also discussed and applied to these sample problems. The semi‐orthogonal functions are found to be an efficient and practical means of achieving very well‐conditioned p‐version finite element matrices.
A study of distributed‐order time fractional diffusion models with continuous distribution weight functions
Authors: Yu Qiang , Turner Ian , Liu Fawang , Moroney Timothy
Published: July 2022

The distributed‐order time fractional diffusion model with Dirichlet nonhomogeneous boundary conditions on a finite domain is considered. Four choices of continuous distribution weight functions with mean μ and standard deviation σ are investigated to study their impact on both the short‐time and long‐time solution behavior. An implicit numerical method implemented on a graded mesh is proposed to solve the model and the stability and convergence analysis are presented. Semi‐analytic solutions are also derived for these distributions to assess the accuracy of the scheme. Numerical results highlight that the four continuous distribution weight functions produce a short‐time solution behavior that is consistent with those solutions from the classical time fractional partial differential equation with fractional order γ* = μ. There are however long‐time differences in the solution behavior that become more distinguishable as σ increases. In particular, we find a smaller value of σ produces more diffuse profiles and the diffusion rate slows as σ increases. Furthermore, the asymptotic behavior of the solution may be influenced by the time‐fractional orders ranging between the smallest nonzero weight order and mean μ for the continuous uniform and raised cosine distribution weight functions, respectively. Similar findings are also observed for the truncated normal and beta distributions.
Prenatal ultrasound findings associated with PIGW variants: One more piece in the FRYNS syndrome puzzle? PIGW‐related prenatal findings
Authors: Ronzoni Luisa , Boito Simona , Meossi Camilla , Cesaretti Claudia , Rinaldi Berardo , Agolini Emanuele , Rizzuti Tommaso , Pezzoli Laura , Silipigni Rosamaria , Novelli Antonio , Iascone Maria , Persico Nicola , Natacci Federica
Published: July 2022

Objective

We describe the prenatal ultrasound findings and autopsy of three fetuses with multiple congenital anomalies (MCA) whose diagnostic workup suggested the same genetic etiology. We conducted a literature review to corroborate the molecular results and find evidence that the identified variants are responsible for the phenotype seen.

Methods

Trio‐based Exome Sequencing (ES) analysis was performed on chorionic villus samples. We reviewed available reports dealing with prenatal manifestations of genes involved in the Glycosylphosphatidylinositols (GPI) biosynthesis defects (GPIBDs).

Results

Prenatal findings shared by all the three pregnancies included facial dysmorphisms, brain malformations of the posterior fossa, skeletal and genitourinary anomalies. ES analysis identified homozygous variants of uncertain significance in PIGW in the three fetuses. Prenatal findings of the three pregnancies overlapped with those previously described for PIGW variants and with those associated with PIGN, PIGV and PIGA variants.

Conclusion

Based on the phenotypic overlap between the prenatal findings in our three cases and other cases with pathogenic variants in other genes involved in GPIBDs, we speculate that the variants identified in the three fetuses are likely causal of their phenotype and that the PIGWclinical spectrum might extend to MCA, mainly involving brain, skeletal and genitourinary systems. Moreover, we suggest that also PIGW could be involved in Fryns/Fryns‐like phenotypes.
Recent advances in morphologically controlled synthesis of graphene oxide‐based nanocomposite as catalyst and fuel additive
Authors: Shahbaz Iqra , Jamil Saba , Bibi Shamsa , Khan Shanza Rauf , Janjua Muhammad Ramzan Saeed Ashraf
Published: July 2022

Nanocomposites become very important because of their reduce size (1–100 nm), large surface area, excellent optical magnetic, and electrical and mechanical properties. In many applications, graphene oxide‐based metallic nanocomposites emerged as an outstanding class of nanomaterials that are used for different applications. (GO‐ZnO) nanocomposite has gained more importance in recent years. The present research study is designed to synthesize nanocomposites and aims to monitor its characteristics and applications. Graphene oxide is synthesized by Hummers' method. Metal salts are used as precursor source of respective metal oxides. Wet chemical synthesis method such as solvothermal/hydrothermal and copreciptation processes is used because of its low cost and easy applications as compared with other processes used in the past, which have been costly and difficult to handle. Scanning electron microscopy (SEM) and X‐ray diffraction (XRD) techniques are used to discriminate GO‐Zinc oxide metallic nanocomposites. XRD is used to investigate the crystal structure, and SEM images showed that the synthesized GO/ZnO nanocomposites is irregular in shape with merged surfaces and the size is 100 nm−1 μm. The dark and light color shows hollow morphology of the nanocomposites, and particles are merged with each other and irregular in shape. The obtained data are statistically analyzed by using regression analysis for the further interpretations. VESTA, MATCH, Origin pro is used for the interpretation of XRD results of synthesized nanocomposites. Applications of metallic (GO/Zn) nanocomposite as catalytic activity and colorimetry, flash point, fire point, cloud point, pour point, specific gravity, and viscosity and for the degradation of Drimarene Red K‐4BL is performed.
Enhancement of the Dielectric Properties of Polyvinyl Alcohol by Adding TiO2Nanoparticles
Authors: El-Gamal Abear Abdullah
Published: July 2022

High dielectric constant nanocomposite polymer films based polyvinyl alcohol (PVA) with different weight ratios of nanoparticles (NPs) TiO2(1.0, 2.5, 5.0, and 10) are prepared by the casting method. The structure of TiO2NPs is studied using TEM and XRD spectra, where the FTIR spectra show a strong interaction between PVA and TiO2NPs. The addition of TiO2NPs to the composites improves their mechanical properties. The dielectric parameters and AC conductivity are explored in the 10 Hz to 107 Hz frequency range at different temperatures. PVA composite films filled with 5.0 wt% TiO2NPs exhibit the highest dielectric constant (ε′) reaching up to 26 at 25 °C and 100 Hz. The origins of the enhanced dielectric properties are investigated using theoretical predictions of the effectiveε′of composites. The activation energy of a dielectric relaxation process is computed. As the temperature rises, the relaxation time lengthens slightly. A conduction mechanism is described based on thermally activated electron hops at the Fermi edge.
A gradient‐free distributed optimization method for convex sum of nonconvex cost functions
Authors: Pang Yipeng , Hu Guoqiang
Published: July 2022

This article presents a special type of distributed optimization problems, where the summation of agents' local cost functions (i.e., global cost function) is convex, but each individual can be nonconvex. Unlike most distributed optimization algorithms by taking the advantages of gradient, the considered problem is allowed to be nonsmooth, and the gradient information is unknown to the agents. To solve the problem, a Gaussian‐smoothing technique is introduced and a gradient‐free method is proposed. We prove that each agent's iterate approximately converges to the optimal solution both with probability 1 and in mean, and provide an upper bound on the optimality gap, characterized by the difference between the functional value of the iterate and the optimal value. The performance of the proposed algorithm is demonstrated by a numerical example and an application in privacy enhancement.
Unified estimation for Cox regression model with nonmonotone missing at random covariates
Authors: Thiessen David Luke , Zhao Yang , Tu Dongsheng
Published: July 2022

This article investigates a unified estimator for Cox regression model (Cox, 1972) when covariate data are missing at random (Rubin, 1976). It extends the idea of using parametric working models (Zhao and Liu, 2021) to extract the partial information contained in the incomplete observations. The working models are flexible and convenient to deal with nonmonotone missing data patterns. It can also incorporate auxiliary variables into the analysis to reduce estimation bias and improve efficiency. The unified estimator is consistent and more efficient than the (weighted) complete case estimator. Similar to multiple imputation (MI) method (Rubin, 1987 and 1996), the proposed method is also based on standard (weighted) complete data analysis and can be easily implemented in standard software. Simulation studies comparing the unified estimator with the substantive model compatible modification of the fully conditional specification MI (SMC‐FCS) estimator (Bartlett et al., 2015) in various settings indicate that the unified estimator is consistent and as efficient as SMC‐FCS estimator. Data from a clinical trial in patients with early breast cancer are analyzed for illustration.
Higher order asymptotic refinements in Bell regressions
Authors: Lemonte Artur J.
Published: July 2022

The discrete Bell distribution and its associated regression model were introduced recently in the statistical literature. The Bell distribution has proved to be a useful alternative to the traditional Poisson distribution, mainly to deal with overdispersion. Likelihood‐based inference on the Bell regression parameters relies on asymptotic assumptions like the sample size going to infinity. In this paper, we focus on the small‐sample case and consider higher order asymptotic refinements in this class of regression models. In particular, we derive the second‐order biases of the maximum likelihood estimators, which are used to define bias‐corrected estimators. The preventive method to bias reducing is also considered. We provide a simple matrix formula for the skewness of the distributions of the maximum likelihood estimators, and also derive a simple matrix formula for the second‐order variance–covariance matrix of the maximum likelihood estimators in this class of regression models. We use Monte Carlo simulations to verify the performance of the proposed methods. Our simulation results suggest that the analytical expressions we derive deliver more reliable results in small‐sized samples. An empirical application to a real data set is considered for illustrative purposes.
The Critical Role of Carbon Nanotubes in Bridging Academic Research to Commercialization of Lithium Batteries
Authors: Zhu Sheng , Ni Jiangfeng
Published: July 2022

Rechargeable lithium batteries have been intensively explored due to their potential to deliver a high energy and stable cycling performance. Yet considerable achievements have been reported on battery performance in lab‐based research, a broad gap from fundamental research to their industrial application needs to be filled. The significant advances in the field of carbon nanotubes over the past decades make it a promising candidate to bridge such a gap. Nevertheless, a systematic and profound understanding of its roles in Li batteries is lacking. In this review, we discuss the critical role of carbon nanotube in developing several lithium techniques such as Li‐ion, Li‐sulfur, and Li‐air cells. The focus is laid on the elevation of device capacity, energy, and cyclic life to meet the practical demand. We hope this paper, together with other recently‐proposed guiding principles, will pave the way for the massive application of carbon nanotube‐based lithium batteries.
Effect of environment‐friendly intercalated Coal and coal gangue on flame‐retardant, antistatic, and mechanical properties of poly(vinyl chloride)/acrylonitrile–styrene–acrylate composites
Authors: Xu Fuqin , He Xiaofang , Hou Zhaoyang , Cao Xinxin , Yang Xiaoyong , Ma Zhihui , Cai Jing , Niu Yapeng
Published: July 2022

Coal‐based environment‐friendly PVC/ASA flame‐retardant and antistatic composites were made by melt blending poly(vinyl chloride)/acrylonitrile–styrene‐acrylate (PVC/ASA) with self‐made alkaline calcium‐based coal gangue thermal stabilizer (Y‐CG) and dimethyl sulfoxide (DMSO) intercalation modified Coal (A‐Coal). The flame‐retardant mechanism of PVC/ASA/A‐Coal/Y‐CG composites was due to incombustible gas, maze effect, carbon residue layer and blowing‐out effect through limiting oxygen index (LOI), vertical combustion (UL‐94) and scanning electron microscope (SEM) test. The results indicated that PVC/ASA/12A‐Coal/10Y‐CG composites had the best flame‐retardant properties with LOI value of 31.8% and can pass the V‐0 rating in the UL‐94 test. After combustion, PVC/ASA/12A‐Coal/10Y‐CG composites formed a dense carbon layer that inhibits gas released and heat transferred. The surface resistivity () and volume resistivity () of PVC/ASA/A‐Coal/Y‐CG composites first decreased and then increased with the increase of A‐Coal content. The and values of PVC/ASA/12A‐Coal/10Y‐CG composites decreased to the minimum values of 5.14 × 106 Ω and 9.05 × 105 Ω·cm. The tensile strength and impact strength of PVC/ASA/A‐Coal/Y‐CG composites first increased and then decreased with A‐Coal content. The tensile strength and impact strength of PVC/ASA/12A‐Coal/10Y‐CG composites reached the maximum of 65.03 MPa and 17.52 kJ/m2, respectively. To sum up, the incorporation of A‐Coal and Y‐CG can reinforce and toughen PVC/ASA composites, but it can also enhance their flame‐retardant, antistatic properties.
Successful treatment of pyruvate kinase deficiency and inflammatory bowel disease comorbid with exocrine pancreatic insufficiency and hypocobalaminaemia in a cat
Authors: Konishi Keisuke , Okazaki Seiji , Kono Shota , Nakamura Takayuki , Ushigusa Takahiro
Published: July 2022

A 3‐year‐old Abyssinian cat presented with chronic diarrhoea and weight loss. Blood examination and abdominal ultrasound examination identified severe macrocytic hypochromic anaemia and thickened intestinal walls. Pyruvate kinase deficiency and inflammatory bowel disease (IBD) were diagnosed based on gene analysis and intestinal biopsy findings, respectively. Additional blood evaluation identified exocrine pancreatic insufficiency (EPI) and hypocobalaminaemia. To eliminate the primary cause of haemolysis, we performed splenectomy, which stabilised the progression of anaemia for approximately 37 days. However, anaemia progressed on day 43 after splenectomy; therefore, 1 mg/kg prednisolone (PO q24h) was administered for stabilising erythrocytes and management of IBD. Significant improvements in the severity of anaemia, echinocyte counts and gastrointestinal clinical signs caused by IBD and EPI were observed with gastrointestinal diet, cobalamin and pancreatic enzymes supplementation. Prednisolone dose was then tapered to 0.5 mg/kg PO every 72 hours. There was no relapse of severe anaemia or signs of IBD or EPI.
Stampedes I: fishnet OPE and octagon Bootstrap with nonzero bridges
Authors: Olivucci Enrico , Vieira Pedro
Published: July 2022

Abstract

Some quantities in quantum field theory are dominated by so-called leading logs and can be re-summed to all loop orders. In this work we introduce a notion of stampede which is a simple time-evolution of a bunch of particles which start their life in a corner — on the very right say — and hop their way to the opposite corner — on the left — through the repeated action of a quantum Hamiltonian. Such stampedes govern leading logs quantities in certain quantum field theories. The leading euclidean OPE limit of correlation functions in the fishnet theory and null double-scaling limits of correlators in $$ \mathcal{N} $$
N
= 4 SYM are notable examples. As an application, we use these results to extend the beautiful bootstrap program of Coronado [1] to all octagons functions with arbitrary diagonal bridge length.
Spurious poles in a finite volume
Authors: Pang Jin-Yi , Ebert Martin , Hammer Hans-Werner , Müller Fabian , Rusetsky Akaki , Wu Jia-Jun
Published: July 2022

Abstract

Using effective-range expansion for the two-body amplitudes may generate spurious sub-threshold poles outside of the convergence range of the expansion. In the infinite volume, the emergence of such poles leads to the inconsistencies in the three-body equations, e.g., to the breakdown of unitarity. We investigate the effect of the spurious poles on the three-body quantization condition in a finite volume and show that it leads to a peculiar dependence of the energy levels on the box size L. Furthermore, within a simple model, it is demonstrated that the procedure for the removal of these poles, which was recently proposed in ref. [1] in the infinite volume, can be adapted to the finite-volume calculations. The structure of the exact energy levels is reproduced with an accuracy that systematically improves order by order in the EFT expansion.
High-fat diet activates splenic NOD1 and enhances neutrophil recruitment and neutrophil extracellular traps release in the spleen of ApoE-deficient mice
Authors: Fernández-García Victoria , González-Ramos Silvia , Avendaño-Ortiz José , Martín-Sanz Paloma , Gómez-Coronado Diego , Delgado Carmen , Castrillo Antonio , Boscá Lisardo
Published: July 2022

In the course of atherogenesis, the spleen plays an important role in the regulation of extramedullary hematopoiesis, and in the control of circulating immune cells, which contributes to plaque progression. Here, we have investigated the role of splenic nucleotide-binding oligomerization domain 1 (NOD1) in the recruitment of circulating immune cells, as well as the involvement of this immune organ in extramedullary hematopoiesis in mice fed on a high-fat high-cholesterol diet (HFD). Under HFD conditions, the absence of NOD1 enhances the mobilization of immune cells, mainly neutrophils, from the bone marrow to the blood. To determine the effect of NOD1-dependent mobilization of immune cells under pro-atherogenic conditions, Apoe−/− and Apoe−/−Nod1−/− mice fed on HFD for 4 weeks were used. Splenic NOD1 from Apoe−/− mice was activated after feeding HFD as inferred by the phosphorylation of the NOD1 downstream targets RIPK2 and TAK1. Moreover, this activation was accompanied by the release of neutrophil extracellular traps (NETs), as determined by the increase in the expression of peptidyl arginine deiminase 4, and the identification of citrullinated histone H3 in this organ. This formation of NETs was significantly reduced in Apoe−/−Nod1−/− mice. Indeed, the presence of Ly6G+ cells and the lipidic content in the spleen of mice deficient in Apoe and Nod1 was reduced when compared to the Apoe−/− counterparts, which suggests that the mobilization and activation of circulating immune cells are altered in the absence of NOD1. Furthermore, confirming previous studies, Apoe−/−Nod1−/− mice showed a reduced atherogenic disease, and diminished recruitment of neutrophils in the spleen, compared to Apoe−/− mice. However, splenic artery ligation reduced the atherogenic burden in Apoe−/− mice an effect that, unexpectedly was lost in Apoe−/−Nod1−/− mice. Together, these results suggest that neutrophil accumulation and activity in the spleen are driven in part by NOD1 activation in mice fed on HFD, contributing in this way to regulating atherogenic progression.
CD146 increases stemness and aggressiveness in glioblastoma and activates YAP signaling
Authors: Liang Yuanke , Voshart Daniëlle , Paridaen Judith T. M. L. , Oosterhof Nynke , Liang Dong , Thiruvalluvan Arun , Zuhorn Inge S. , den Dunnen Wilfred F. A. , Zhang Guojun , Lin Haoyu , Barazzuol Lara , Kruyt Frank A. E.
Published: July 2022

Glioblastoma (GBM), a highly malignant and lethal brain tumor, is characterized by diffuse invasion into the brain and chemo-radiotherapy resistance resulting in poor prognosis. In this study, we examined the involvement of the cell adhesion molecule CD146/MCAM in regulating GBM aggressiveness. Analyses of GBM transcript expression databases revealed correlations of elevated CD146 levels with higher glioma grades, IDH-wildtype and unmethylated MGMT phenotypes, poor response to chemo-radiotherapy and worse overall survival. In a panel of GBM stem cells (GSCs) variable expression levels of CD146 were detected, which strongly increased upon adherent growth. CD146 was linked with mesenchymal transition since expression increased in TGF-ß-treated U-87MG cells. Ectopic overexpression of CD146/GFP in GG16 cells enhanced the mesenchymal phenotype and resulted in increased cell invasion. Conversely, GSC23-CD146 knockouts had decreased mesenchymal marker expression and reduced cell invasion in transwell and GBM-cortical assembloid assays. Moreover, using GSC23 xenografted zebrafish, we found that CD146 depletion resulted in more compact delineated tumor formation and reduced tumor cell dissemination. Stem cell marker expression and neurosphere formation assays showed that CD146 increased the stem cell potential of GSCs. Furthermore, CD146 mediated radioresistance by stimulating cell survival signaling through suppression of p53 expression and activation of NF-κB. Interestingly, CD146 was also identified as an inducer of the oncogenic Yes-associated protein (YAP). In conclusion, CD146 carries out various pro-tumorigenic roles in GBM involving its cell surface receptor function, which include the stimulation of mesenchymal and invasive properties, stemness, and radiotherapy resistance, thus providing an interesting target for therapy.
Influence of intermediate roll shifting on strip shape in a CVC-6 tandem cold mill based on a 3D multi-stand FE model
Authors: Li Lianjie , Xie Haibo , Zhang Tao , Pan Di , Li Xingsheng , Chen Fenghua , Liu Tianwu , Liu Xu , Liu Hongqiang , Sun Li , Jiang Zhengyi
Published: July 2022

Intermediate roll shifting (IRS) is widely used for improving the strip shape in the six-high tandem cold mill, but most related studies are limited to a single stand. To fill the knowledge gap, a three-dimensional (3D) multi-stand elastic–plastic finite element (FE) model was developed for a continuously variable crown (CVC)-6 tandem cold mill using data transfer, which was then validated by industrial experimental results. Based on this FE model, the effects of the IRS on the strip crown, strip flatness, loaded roll gap profile and contact normal stress between rolls at each stand were quantitatively analysed. The results show that from Stand 1 (S1) to Stand 5 (S5), the regulation ability of the IRS on the strip crown shows a decreasing trend, which depends on the strip plastic rigidity; in contrast, the regulation ability on the quadratic flatness experiences an obvious increase from S1 to Stand 4 (S4), then a drop at S5, while the IRS exerts little effect on the quartic flatness and quartic crown of the loaded roll gap. Moreover, the most uniform distribution of contact normal stress emerges at different IRSs from S1 to S5. These findings can contribute to a better understanding of the role of the IRS in controlling the strip shape during tandem cold rolling (TCR).
Going deeper into the toxicokinetics of synthetic cannabinoids: in vitro contribution of human carboxylesterases
Authors: Wagmann Lea , Stiller Rebecca G. , Fischmann Svenja , Westphal Folker , Meyer Markus R.
Published: July 2022

Synthetic cannabinoids (SC) are new psychoactive substances known to cause intoxications and fatalities. One reason may be the limited data available concerning the toxicokinetics of SC, but toxicity mechanisms are insufficiently understood so far. Human carboxylesterases (hCES) are widely known to play a crucial role in the catalytic hydrolysis of drugs (of abuse). The aim of this study was to investigate the in vitro contribution of hCES to the metabolism of the 13 SC 3,5-AB-5F-FUPPYCA, AB-5F-P7AICA, A-CHMINACA, DMBA-CHMINACA, MBA-CHMINACA, MDMB-4F-BINACA, MDMB-4en-PINACA, MDMB-FUBICA, MDMB-5F-PICA, MMB-CHMICA, MMB-4en-PICA, MMB-FUBINACA, and MPhP-5F-PICA. The SC were incubated with recombinant hCES1b, hCES1c, or hCES2 and analyzed by liquid chromatography–ion trap mass spectrometry to assess amide or ester hydrolysis in an initial activity screening. Enzyme kinetic studies were performed if sufficient hydrolysis was observed. No hydrolysis of the amide linker was observed using those experimental conditions. Except for MDMB-5F-PICA, ester hydrolysis was always detected if an ester group was present in the head group. In general, SC with a terminal ester bearing a small alcohol part and a larger acyl part showed higher affinity to hCES1 isozymes. Due to the low hydrolysis rates, enzyme kinetics could not be modeled for the SC with a tert-leucine-derived moiety, but hydrolysis reactions of MPhP-5F-PICA and of those containing a valine-derived moiety followed classic Michaelis–Menten kinetics. In conclusion, drug–drug/drug–food interactions or hCES polymorphisms may prolong the half-life of SC and the current results help to estimate the risk of toxicity in the future after combining them with activity and clinical data.
Targeted detection of cancer cells during biopsy allows real-time diagnosis of pulmonary nodules
Authors: Kennedy Gregory T. , Azari Feredun S. , Bernstein Elizabeth , Nadeem Bilal , Chang Ashley , Segil Alix , Sullivan Neil , Encarnado Emmanuel , Desphande Charuhas , Kucharczuk John C. , Leonard Kaela , Low Philip S. , Chen Silvia , Criton Aline , Singhal Sunil
Published: July 2022

Background

The diagnostic yield of biopsies of solitary pulmonary nodules (SPNs) is low, particularly in sub-solid lesions. We developed a method (NIR-nCLE) to achieve cellular level cancer detection during biopsy by integrating (i) near-infrared (NIR) imaging using a cancer-targeted tracer (pafolacianine), and (ii) a flexible NIR confocal laser endomicroscopy (CLE) system that can fit within a biopsy needle. Our goal was to assess the diagnostic accuracy of NIR-nCLE ex vivo in SPNs.

Methods

Twenty patients with SPNs were preoperatively infused with pafolacianine. Following resection, specimens were inspected to identify the lesion of interest. NIR-nCLE imaging followed by tissue biopsy was performed within the lesion and in normal lung tissue. All imaging sequences (n = 115) were scored by 5 blinded raters on the presence of fluorescent cancer cells and compared to diagnoses by a thoracic pathologist.

Results

Most lesions (n = 15, 71%) were adenocarcinoma-spectrum malignancies, including 7 ground glass opacities (33%). Mean fluorescence intensity (MFI) by NIR-nCLE for tumor biopsy was 20.6 arbitrary units (A.U.) and mean MFI for normal lung was 6.4 A.U. (p < 0.001). Receiver operating characteristic analysis yielded a high area under the curve for MFI (AUC = 0.951). Blinded raters scored the NIR-nCLE sequences on the presence of fluorescent cancer cells with sensitivity and specificity of 98% and 97%, respectively. Overall diagnostic accuracy was 97%. The inter-observer agreement of the five raters was excellent (κ = 0.95).

Conclusions

NIR-nCLE allows sensitive and specific detection of cancer cells in SPNs. This technology has far-reaching implications for diagnostic needle biopsies and intraprocedural decision-making.
Radionuclide imaging and therapy directed towards the tumor microenvironment: a multi-cancer approach for personalized medicine
Authors: van der Heide Circe D. , Dalm Simone U.
Published: July 2022

Targeted radionuclide theranostics is becoming more and more prominent in clinical oncology. Currently, most nuclear medicine compounds researched for cancer theranostics are directed towards targets expressed in only a small subset of cancer types, limiting clinical applicability. The identification of cancer-specific targets that are (more) universally expressed will allow more cancer patients to benefit from these personalized nuclear medicine–based interventions. A tumor is not merely a collection of cancer cells, it also comprises supporting stromal cells embedded in an altered extracellular matrix (ECM), together forming the tumor microenvironment (TME). Since the TME is less genetically unstable than cancer cells, and TME phenotypes can be shared between cancer types, it offers targets that are more universally expressed. The TME is characterized by the presence of altered processes such as hypoxia, acidity, and increased metabolism. Next to the ECM, the TME consists of cancer-associated fibroblasts (CAFs), macrophages, endothelial cells forming the neo-vasculature, immune cells, and cancer-associated adipocytes (CAAs). Radioligands directed at the altered processes, the ECM, and the cellular components of the TME have been developed and evaluated in preclinical and clinical studies for targeted radionuclide imaging and/or therapy. In this review, we provide an overview of the TME targets and their corresponding radioligands. In addition, we discuss what developments are needed to further explore the TME as a target for radionuclide theranostics, with the hopes of stimulating the development of novel TME radioligands with multi-cancer, or in some cases even pan-cancer, application.
Deep Learning–driven classification of external DICOM studies for PACS archiving
Authors: Jonske Frederic , Dederichs Maximilian , Kim Moon-Sung , Keyl Julius , Egger Jan , Umutlu Lale , Forsting Michael , Nensa Felix , Kleesiek Jens
Published: July 2022

Objectives

Over the course of their treatment, patients often switch hospitals, requiring staff at the new hospital to import external imaging studies to their local database. In this study, the authors present MOdality Mapping and Orchestration (MOMO), a Deep Learning–based approach to automate this mapping process by combining metadata analysis and a neural network ensemble.

Methods

A set of 11,934 imaging series with existing anatomical labels was retrieved from the PACS database of the local hospital to train an ensemble of neural networks (DenseNet-161 and ResNet-152), which process radiological images and predict the type of study they belong to. We developed an algorithm that automatically extracts relevant metadata from imaging studies, regardless of their structure, and combines it with the neural network ensemble, forming a powerful classifier. A set of 843 anonymized external studies from 321 hospitals was hand-labeled to assess performance. We tested several variations of this algorithm.

Results

MOMO achieves 92.71% accuracy and 2.63% minor errors (at 99.29% predictive power) on the external study classification task, outperforming both a commercial product (82.86% accuracy, 1.36% minor errors, 96.20% predictive power) and a pure neural network ensemble (72.69% accuracy, 10.3% minor errors, 99.05% predictive power) performing the same task. We find that the highest performance is achieved by an algorithm that combines all information into one vote-based classifier.

Conclusion

Deep Learning combined with metadata matching is a promising and flexible approach for the automated classification of external DICOM studies for PACS archiving.

Key Points

• The algorithm can successfully identify 76 medical study types across seven modalities (CT, X-ray angiography, radiographs, MRI, PET (+CT/MRI), ultrasound, and mammograms).

• The algorithm outperforms a commercial product performing the same task by a significant margin (> 9% accuracy gain).

• The performance of the algorithm increases through the application of Deep Learning techniques.
Should the early surgery threshold be moved to 72 h in over-85 patients with hip fracture? A single-center retrospective evaluation on 941 patients
Authors: De Luca Alessandro , Murena Luigi , Zanetti Michela , De Colle Paolo , Ratti Chiara , Canton Gianluca
Published: July 2022

Aim

Aim of the study was to assess whether early surgery and other clinical and orthogeriatric parameters could affect mortality rate in hip fracture patients aged > 85.

Materials and methods

Data regarding a 42-month period were retrospectively obtained from the institutional medical records and registry data. Gender, age, fracture pattern, surgical technique, type of anesthesia, timing of surgical intervention (within 24, 48 or 72 h from admission), days of hospitalization, mortality rate divided in intra-hospital, at 30 days and at 1 year were collected for the whole population. Some additional data were collected for an orthogeriatric subgroup.

Results

941 patients were considered, with a mean age of 89 years. Surgery was performed within 24, 48 and 72 h in 24.4%, 54.5% and 66.1% of cases, respectively. Intra-hospital mortality rate resulted to be 3.4%, while mortality at 30 days and 1 year resulted to be 4.5% and 31%, respectively. Early surgery within 48 and 72 h were significantly associated with a lower intra-hospital and 30-day mortality rate. In the orthogeriatric subgroup (394 patients), a significant association with a higher mortality rate was found for general anesthesia, number of comorbidities, ADL (Activities of Daily Living) < 3, transfer to other departments.

Conclusions

In over-85 hip fracture patients, the threshold for early surgery might be moved to 72 h to allow patients pre-operative stabilization and medical optimization as intra-hospital and 30-day mortality rates remain significantly lower. Advanced age, male sex, number of comorbidities, pre-operative dependency in ADL, general anesthesia, length of hospitalization and transfer to other departments were significantly related to mortality rate.
The clinical relevance of serum versus CSF NMDAR autoantibodies associated exclusively with psychiatric features: a systematic review and meta-analysis of individual patient data
Authors: Blackman Graham , Lim Mao Fong , Pollak Thomas , Al-Diwani Adam , Symmonds Mkael , Mazumder Asif , Carter Ben , Irani Sarosh , David Anthony
Published: July 2022

Background

A variety of psychiatric syndromes are associated with NMDAR autoantibodies; however, their clinical relevance when only present in the serum is unclear. We explored whether patients with CSF NMDAR autoantibodies could be distinguished from patients with serum-only NMDAR autoantibodies.

Methods

The electronic databases MEDLINE, EMBASE, PubMed, and PsycINFO were searched. Articles reporting adult patients with isolated psychiatric features and positive for NMDAR autoantibodies with relevant investigations were included. Patient level meta-analysis compared patients positive for CSF NMDAR autoantibodies with patients positive for serum NMDAR autoantibodies, but negative for CSF NMDAR autoantibodies. Dichotomous data were analysed using crude odds ratios (OR), whilst continuous data were analysed using Mann–Whitney Test (U). The protocol was prospectively registered (CRD42018082210).

Results

Of 4413 publications, 42 were included, reporting 79 patients. Median age was 34 years (IQR 19 years); 56% (45/79) were female and 24% (16/68) had a tumour. In total, 41 patients were positive for CSF autoantibodies and 20 were positive for serum-only autoantibodies. Patients with CSF autoantibodies were significantly more likely to be female (p < 0.001) and have a rapid (< 3 month) onset of symptoms (p = 0.02) than patients with serum-only autoantibodies. They were also more likely to present with psychosis (p < 0.001), exhibit EEG (p = 0.006), MRI (p = 0.002), and CSF (p = 0.001) abnormalities, but less likely to present with insomnia (p = 0.04).

Conclusions

Patients with an isolated psychiatric syndrome with CSF NMDAR autoantibodies can potentially be distinguished from those with serum-only NMDAR autoantibodies based on clinicodemographic and investigation findings.
Association between lipid trajectories during pregnancy and risk of postpartum glucose intolerance after gestational diabetes mellitus: a cohort study
Authors: Yang Zhuofan , Li Zhuyu , Cheng Yunjiu , Chen Peisong , Wang Dongyu , Chen Haitian , Chen Wei , Wang Zilian
Published: July 2022

Aims

To assess lipid trajectories throughout pregnancy in relation to early postpartum glucose intolerance in women with gestational diabetes mellitus (GDM).

Methods

This prospective cohort study included 221 Chinese women with GDM who completed plasma lipid test in each trimester of pregnancy and oral glucose tolerance test at 6–9 weeks postdelivery between January 1, 2018 and January 8, 2020. Using the group-based trajectory modeling, total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-c), and high-density lipoprotein-cholesterol(HDL-c) were identified separately as three trajectories: low, moderate, and high trajectory. The associations between lipid trajectories and early postpartum glucose intolerance were all evaluated.

Results

Seventy-three participants developed postpartum glucose intolerance. For patients in low, moderate and high trajectory, the incidence of postpartum glucose intolerance was 38.4%, 34.9%, and 17.9%, respectively. GDM women with lower LDL-c trajectories presented a higher risk of postpartum glucose intolerance. The adjusted odds ratio (95% CI) for glucose intolerance was 3.14 (1.17–8.39) in low LDL-c trajectory and 2.68 (1.05–6.85) in moderate trajectory when compared with the high one. However, TC trajectory was not associated with the risk of postpartum glucose intolerance, nor were TG trajectory and HDL-c trajectory. Moreover, a significant difference of insulin sensitivity was observed in participants with different LDL-c trajectories; participants in high LDL-c trajectory had the highest insulin sensitivity, whereas the women in low LDL-c trajectory had the lowest insulin sensitivity (P = 0.02).

Conclusions

The high trajectory of LDL-c during pregnancy may play a protective role on postpartum glucose intolerance in women with GDM. Further studies are warranted to explore the underlying mechanism.

Trial registration The study was reviewed and approved by the Institutional Review Board of The First Affiliated Hospital of Sun Yat-sen University (reference number: [2014]No. 93). All participants provided written informed consent forms, and the ethics committee approved this consent procedure.
Interlaboratory comparisons of chemical measurements: Quo Vadis?
Authors: Meija Juris , Possolo Antonio
Published: July 2022

In numerous articles and editorials, many of which were published in ACQUAL, Paul De Bièvre laid out challenges time and again about how the application of statistical methods can help improve our understanding of chemical measurements. Paul’s insights and incisive criticism were as illuminating and as provocative as in all other areas that he looked into—from counting to consensus building, from the validity of common statistical assumptions to the impact of model uncertainty. This memorial contribution briefly revisits some of these concerns illustrated by examples from interlaboratory comparisons and proposes an optimistic outlook for how the statistical arts practised in close collaboration between chemist and statistician will continue to add value to the chemical sciences.
Highly perturbed genes and hub genes associated with type 2 diabetes in different tissues of adult humans: a bioinformatics analytic workflow
Authors: De Silva Kushan , Demmer Ryan T. , Jönsson Daniel , Mousa Aya , Forbes Andrew , Enticott Joanne
Published: July 2022

Type 2 diabetes (T2D) has a complex etiology which is not yet fully elucidated. The identification of gene perturbations and hub genes of T2D may deepen our understanding of its genetic basis. We aimed to identify highly perturbed genes and hub genes associated with T2D via an extensive bioinformatics analytic workflow consisting of five steps: systematic review of Gene Expression Omnibus and associated literature; identification and classification of differentially expressed genes (DEGs); identification of highly perturbed genes via meta-analysis; identification of hub genes via network analysis; and downstream analysis of highly perturbed genes and hub genes. Three meta-analytic strategies, random effects model, vote-counting approach, and p value combining approach, were applied. Hub genes were defined as those nodes having above-average betweenness, closeness, and degree in the network. Downstream analyses included gene ontologies, Kyoto Encyclopedia of Genes and Genomes pathways, metabolomics, COVID-19-related gene sets, and Genotype-Tissue Expression profiles. Analysis of 27 eligible microarrays identified 6284 DEGs (4592 downregulated and 1692 upregulated) in four tissue types. Tissue-specific gene expression was significantly greater than tissue non-specific (shared) gene expression. Analyses revealed 79 highly perturbed genes and 28 hub genes. Downstream analyses identified enrichments of shared genes with certain other diabetes phenotypes; insulin synthesis and action-related pathways and metabolomics; mechanistic associations with apoptosis and immunity-related pathways; COVID-19-related gene sets; and cell types demonstrating over- and under-expression of marker genes of T2D. Our approach provided valuable insights on T2D pathogenesis and pathophysiological manifestations. Broader utility of this pipeline beyond T2D is envisaged.
Interleukin-6 as a prognostic biomarker of clinical outcomes after traumatic brain injury: a systematic review
Authors: Ooi Setthasorn Zhi Yang , Spencer Robert James , Hodgson Megan , Mehta Samay , Phillips Nicholas Lloyd , Preest Gwilym , Manivannan Susruta , Wise Matt P , Galea James , Zaben Malik
Published: July 2022

Traumatic brain injury (TBI) is a major cause of mortality and morbidity worldwide. There are currently no early biomarkers for prognosis in routine clinical use. Interleukin-6 (IL-6) is a potential biomarker in the context of the established role of neuroinflammation in TBI recovery. Therefore, a systematic review of the literature was performed to assess and summarise the evidence for IL-6 secretion representing a useful biomarker for clinical outcomes. A multi-database literature search between January 1946 and July 2021 was performed. Studies were included if they reported adult TBI patients with IL-6 concentration in serum, cerebrospinal fluid (CSF) and/or brain parenchyma analysed with respect to functional outcome and/or mortality. A synthesis without meta-analysis is reported. Fifteen studies were included, reporting 699 patients. Most patients were male (71.7%), and the pooled mean age was 40.8 years; 78.1% sustained severe TBI. Eleven studies reported IL-6 levels in serum, six in CSF and one in the parenchyma. Five studies on serum demonstrated higher IL-6 concentrations were associated with poorer outcomes, and five showed no signification association. In CSF studies, one found higher IL-6 levels were associated with poorer outcomes, one found them to predict better outcomes and three found no association. Greater parenchymal IL-6 was associated with better outcomes. Despite some inconsistency in findings, it appears that exaggerated IL-6 secretion predicts poor outcomes after TBI. Future efforts require standardisation of IL-6 measurement practices as well as assessment of the importance of IL-6 concentration dynamics with respect to clinical outcomes, ideally within large prospective studies. Prospero registration number: CRD42021271200
Regeneration of periodontal bone defects with mesenchymal stem cells in animal models. Systematic review and meta-analysis
Authors: Chauca-Bajaña Luis , Velasquez-Ron Byron , Tomás-Carmona Inmaculada , Camacho-Alonso Fabio , Pérez-Jardón Alba , Pérez‐Sayáns Mario
Published: July 2022

The aim of this study was to evaluate the efficacy of mesenchymal stem cells (MSCs) in the regeneration of periodontal bone defects in animal models. A systematic review and meta-analysis were conducted following the PRISMA guidelines, and the study was recorded in PROSPERO under reference number CDR42021247462. The PICO question was: is periodontal regeneration (cementum, periodontal ligament and alveolar bone) with MSCs more effective than other techniques? Three groups were considered: Group 1: MSCs alone or mixed with regenerative materials. Group 2: only regenerative materials. Group 3: no regenerative material nor MSCs. The search was conducted using MeSH with a total of 18 articles for qualitative analysis and 5 for quantitative analysis. For the meta-analysis, a modification of the effect size algorithm was developed, which considered a comparison of means between treatments using the Student's t sample distribution. When comparing the effect size between Group 1 and Group 2, the effect size for the new cementum was 2.83 mm with an estimated confidence interval of 95% (CI 95%) between 0.48 and 5.17 mm. When considering the fit to a random-effects model, the combined variance (τ2) was 6.1573 mm, with a standard deviation (SD) of 5.6008 mm and a percentage of total heterogeneity I2 of 92.33% (p < 0.0001). For new bone, the effect size was 0.88 mm, CI 95% − 0.25 to 2.01 mm, τ2 = 1.3108 mm (SD = 1.2021 mm) and I2 = 80.46%, p = 0.0004). With regard to the new periodontal ligament, it was not possible for the meta-analysis to be performed. MSCs have a greater capacity for tissue regeneration in root cementum than in alveolar bone compared to other regenerative materials.