bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of the predominant human NK cell effector subset mediating ADCC against HIV‐infected targets coated with BNAbs or plasma from PLWH
Authors: Tomescu Costin , Kroll Kyle , Colon Krystal , Papasavvas Emmanouil , Frank Ian , Tebas Pablo , Mounzer Karam , Reeves Roger Keith , Montaner Luis J.
Published: June 2021

The potential of immunotherapy strategies utilizing broadly neutralizing antibodies (BNAbs), such as 3BNC117 and 10‐1074, to limit viral replication while also facilitating clearance of HIV infected cells has heightened interest in identifying the predominant NK effector subset(s) capable of mediating antibody dependent cellular cytotoxicity (ADCC). Utilizing advanced polychromatic flow cytometry, we identified that CD57 positive NK cells from ART‐suppressed in People Living With HIV (PLWH) expressed significantly higher levels of the CD16 FcγR receptor, 2B4 ADCC coreceptor, and HLA‐DR activation marker while NKG2C positive NK cells expressed significantly higher levels of the CD2 ADCC coreceptor (p < 0.001, n = 32). Functionally, CD57 positive NK cells from ART‐suppressed PLWH with either high or low NKG2C expansion exhibited significantly enhanced degranulation and IFN‐γ production against heterologous gp120‐coated ADCC targets coated with HIV reference plasma compared to CD57 negative NK cells (p = 0.0029, n = 11). CD57 positive NK cells from control donors lacking NKG2C expansion also exhibited significantly more degranulation and IFN‐γ production at every timepoint tested against both heterologous ADCC targets (p = 0.019, n = 9) and HIV‐1 infected autologous CD4+ primary T cells coated with BNAbs. Together, our data support CD57 positive and NKG2C positive NK cells as the predominant ADCC effector subsets capable of targeting HIV‐infected CD4+ cells in the presence of 3BNC117 and 10‐1074 immunotherapy.
Generation of Catalytically Active Gold Nanocrystals in Water Induced with Ferrocene Carboxylate
Authors: Wang Changlong , Brudo Agathe , Ducrot Laurine , Fu Fangyu , Ruiz Jaime , Escobar Ane , Martinez‐Villacorta Angel , Moya Sergio , Astruc Didier
Published: June 2021

The fabrication and properties of anisotropic gold nanoparticles (AuNPs) are of great interest from fundamental and application standpoints. Whereas various neutral ferrocene derivatives have been shown to reduce AuIII to Au0NPs owing to slightly exergonic electron transfer in biphasic systems, the question remained open for water soluble ferrocenes containing electron withdrawing substituents increasing the FeIII/FeII oxidation potential. Here, it is shown that reaction of sodium ferrocene carboxylate, NaFcCO2, alone, does not reduce H[AuIIICl4] to stable AuNPs under ambient conditions in water. On the other hand, reaction between NaFcCO2 and H[AuIIICl4] in water in the presence of poly (vinyl pyrrolidone) (PVP), citrate or other 1,2,3‐triazole (trz)‐containing stabilizers is shown to produce catalytically active Au nanocrystals with various shapes. EDX results confirm the fixation of the ferrocenyl carboxylate ligand onto the AuNP surface. 4‐nitrophenol reduction to 4‐aminophenol by Na[BH4] in water proceeds in the presence of the various stabilizers, without induction time in most cases, which confirms the weakness of the ferrocenyl carboxylate ligand bonded to the AuNP surface and the favorable role of ferrocenyl carboxylate ligand for catalysis at the AuNP surface.
Crystal Structures of Tetramesityl‐Substituted Tetracyclopenta[def,jkl,pqr,vwx]tetraphenylene
Authors: Miyoshi Hirokazu , Hisaki Ichiro , Tobe Yoshito
Published: June 2021

Crystal structures of tetramesityl‐substituted tetracyclopenta[def,jkl,pqr,vwx]tetraphenylene (TCPTP) derivative were determined for crystals containing different solvents, CHCl3, CH2Cl2, acetone, and benzene at different temperatures to discuss the conjugation modes in the antiaromatic system, i. e., whether it adopts a D2h structure consisting of local aromatic sextets and quinodimethane substructures or a D4h double annulenenoid structure. The structures of the TCPTP core in all crystals determined at 113 K or 93 K resemble those of the theoretical D2h geometry, whereas the bond lengths at room temperature (293 K) adopt averaged values of the theoretical D2h and D4h geometries. These results are interpreted in terms of disorder of two perpendicularly oriented D2h structures at room temperature and support the theoretical prediction which favours the D2h geometry. The slightly different bond length distributions in the crystals are ascribed to the different space in the vicinity of the molecule which allows the molecule to adopt the two orientations in different occupancies.
Nickel‐Catalyzed Asymmetric Hydrogenation of Hydrazones
Authors: Li Bowen , Liu Dan , Hu Yanhua , Chen Jianzhong , Zhang Zhenfeng , Zhang Wanbin
Published: June 2021

An efficient nickel‐catalyzed asymmetric hydrogenation of hydrazones to chiral hydrazines has been realized with up to 99 % yield and 99.4 : 0.6 er. Deuterium labelling experiments indicated that the hydrazone substrates undergo imine‐enamine tautomerization in the mixed solvents. Studies on the effects of acids revealed that the required acid assistance promoted the dissociation of the active nickel catalyst in the catalytic cycle.
Recent advances in microbial capture of hydrogen sulfide from sour gas via sulfur‐oxidizing bacteria
Authors: Chen Zheng , Yang Gama , Hao Xuemi , Samak Nadia A. , Jia Yunpu , Peh Sumit , Mu Tingzhen , Yang Maohua , Xing Jianmin
Published: June 2021

Biological desulfurization offers several remarkably environmental advantages of operation at ambient temperature and atmospheric pressure, no demand of toxic chemicals as well as the formation of biologically re‐usable sulfur (S0), which has attracted increasing attention compared to conventionally physicochemical approaches in removing hydrogen sulfide from sour gas. However, the low biomass of SOB, the acidification of process solution, the recovery of SOB, and the selectivity of bio‐S0 limit its industrial application. Therefore, more efforts should be made in the improvement of the BDS process for its industrial application via different research perspectives. This review summarized the recent research advances in the microbial capture of hydrogen sulfide from sour gas based on strain modification, absorption enhancement, and bioreactor modification. Several efficient solutions to limitations for the BDS process were proposed, which paved the way for the future development of BDS industrialization.
A new optimization technique to solve the latency aware controller placement problem in software defined networks
Authors: Dhar Mili , Bhattacharyya Bidyut K. , Kanti Debbarma Mrinal , Debbarma Swapan
Published: June 2021

Software defined networking (SDN) is a modern and upcoming standard in today's network as it centralizes the network intelligence by separating the control plane from the forwarding plane. Placing a controller in an appropriate location and minimizing the switch to controller (SC) latency are important factors in SDN. In this article, we proposed a mathematical algorithm to form the clusters and placed one controller in each cluster to shorten the worst‐case SC latency. We have proposed a technique called the “$‐method” by using the distance matrix of the network nodes and placed a “$” whenever we have found the matrix element is greater than a given maximum distance. Initially, the maximum distance is calculated using the center of mass method that we have developed for minimizing the average SC latency. Our method guarantees that it will generate the minimum worst‐case SC latency efficiently that one could ever achieve for a different number of controller placement. Simulation has been done under some real‐world network topologies from the dataset of Internet Topology Zoo. Our result shows that the “$‐method” performs better compared with other existing algorithms in terms of worst‐case SC latency minimization with less number of controllers. Further, we have analyzed our method for the failure mode of a controller by assigning the switches of that failed controller to its nearest controllers which shows that our method also performs better in terms of network fault tolerance and improves network resilience.
Effect of slurry ice during storage on myofibrillar protein of Pseudosciaena crocea
Authors: Guan Feng , Chen Yirui , Zhao Simin , Chen Zhuo , Yu Chen , Yuan Yongjun
Published: June 2021

In order to explore the effect of slurry ice on myofibrillar protein of Pseudosciaena crocea, the changes in myofibrillar protein and muscle microstructure during storage were studied with crushed ice as a control. During the storage period, the rate of decrease in myofibrillar protein content, Ca2+‐ATPase activity, and total sulfhydryl groups in the slurry ice group was lower than in the control group (p < .05). There was a significant linear correlation between the hydrophobicity and the storage time (Rcrushed ice (4℃) = 0.9881, Rslurry ice (4℃) = 0.9878, Rslurry ice (−1℃) = 0.9674), and trichloroacetic acid (TCA) soluble peptide content was lower than in the control group at the same time. Slurry ice (−1℃) was optimal in maintaining protein content in P. crocea; the arrangement of myofibrils in P. crocea treated by slurry ice was compact and the gaps were small. Slurry ice can delay the denaturation and degradation of fish myofibrillar protein and maintain its quality.
Study on relationship between bacterial diversity and quality of Huangjiu (Chinese Rice Wine) fermentation
Authors: Xie Guangfa , Zheng Huajun , Qiu Zheling , Lin Zichen , Peng Qi , Dula Bealu Girma , Elsheery Nabil Ibrahim , Lu Yin , Shen Chi , Fu Jianwei , Yang Huanyi , Han Jiongping , Lu Jian , Liu Guanming
Published: June 2021

Huangjiu (Chinese rice wine) is brewed in an open environment, where bacteria play an important role during the fermentation process. In this study, bacterial community structure and composition changes in the fermented mash liquid of mechanized Huangjiu, well‐fermented manual Huangjiu (wines of good qualities), and poorly fermented manual Huangjiu (wines of poor qualities: spoilage, high acidity, low alcohol content) in different fermentation stages from Guyuelongshan Shaoxing Huangjiu company were analyzed via metagenomic sequencing. And bacterial metabolic difference was analyzed via gene prediction of metabolic pathway enzymes. The results showed that the bacterial diversity degree was abundant, and the number of bacterial species in every sample was approximately 200–400. Lactic acid bacteria (LAB) dominated the bacterial community of Huangjiu fermentation, and lactobacillus was predominant species in well‐fermented Huangjiu while Lactobacillus brevis had an absolute dominance in spoilage Huangjiu. Further, gene prediction revealed that transformation of malate to pyruvate and lactate anabolism was more active in mash liquid of well‐fermented manual Huangjiu, while acetate accumulation was stronger in mash liquid of poorly fermented manual Huangjiu, which explained acidity excess reason in poorly fermented Huangjiu at gene level.
Comparison of genetic risk prediction models to improve prediction of coronary heart disease in two large cohorts of the MONICA/KORA study
Authors: Bauer Alina , Zierer Astrid , Gieger Christian , Büyüközkan Mustafa , Müller‐Nurasyid Martina , Grallert Harald , Meisinger Christa , Strauch Konstantin , Prokisch Holger , Roden Michael , Peters Annette , Krumsiek Jan , Herder Christian , Koenig Wolfgang , Thorand Barbara , Huth Cornelia
Published: June 2021

It is still unclear how genetic information, provided as single‐nucleotide polymorphisms (SNPs), can be most effectively integrated into risk prediction models for coronary heart disease (CHD) to add significant predictive value beyond clinical risk models. For the present study, a population‐based case‐cohort was used as a trainingset (451 incident cases, 1488 noncases) and an independent cohort as testset (160 incident cases, 2749 noncases). The following strategies to quantify genetic information were compared: A weighted genetic risk score including Metabochip SNPs associated with CHD in the literature (GRSMetabo); selection of the most predictive SNPs among these literature‐confirmed variants using priority‐Lasso (PLMetabo); validation of two comprehensive polygenic risk scores: GRSGola based on Metabochip data, and GRSKhera (available in the testset only) based on cross‐validated genome‐wide genotyping data. We used Cox regression to assess associations with incident CHD. C‐index, category‐free net reclassification index (cfNRI) and relative integrated discrimination improvement (IDIrel) were used to quantify the predictive performance of genetic information beyond Framingham risk score variables. In contrast to GRSMetabo and PLMetabo, GRSGola significantly improved the prediction (delta C‐index [95% confidence interval]: 0.0087 [0.0044, 0.0130]; IDIrel: 0.0509 [0.0131, 0.0894]; cfNRI improved only in cases: 0.1761 [0.0253, 0.3219]). GRSKhera yielded slightly worse prediction results than GRSGola.
Multitrait transcriptome‐wide association study (TWAS) tests
Authors: Feng Helian , Mancuso Nicholas , Pasaniuc Bogdan , Kraft Peter
Published: June 2021

Multitrait tests can improve power to detect associations between individual single‐nucleotide polymorphisms (SNPs) and several related traits. Here, we develop methods for multi‐SNP transcriptome‐wide association (TWAS) tests to test the association between predicted gene expression levels and multiple phenotypes. We show that the correlation in TWAS test statistics for multiple phenotypes has the same form as multitrait statistics for the single‐SNP setting. Thus, established methods for combining single‐SNP test statistics across multiple traits can be extended directly to the TWAS setting. We performed an extensive evaluation across eight multitrait methods in simulations that varied gene‐phenotype effect sizes in addition to the underlying covariance structure among the phenotypes. We found that all multitrait TWAS tests have well‐calibrated Type I error (except ASSET, which can have a slightly elevated or depressed Type I error rate). Our results show that multitrait TWAS can improve statistical power compared with multiple single‐trait TWAS followed by Bonferroni correction. To illustrate our approach to real data, we conducted a multitrait TWAS of four circulating lipid traits from the Global Lipids Genetics Consortium. We found that our multitrait Wald TWAS approach identified 506 genes associated with lipid levels compared with 87 identified through Bonferroni‐corrected single‐trait TWAS. Overall, we find that our proposed multitrait TWAS framework outperforms single‐trait approaches to identify new genetic associations, especially for functionally correlated phenotypes and phenotypes with overlapping genome‐wide association studies samples, leading to insights into the genetic architecture of multiple phenotypes.
Conflict exposure and health: Evidence from the Gaza Strip
Authors: Di Maio Michele , Leone Sciabolazza Valerio
Published: June 2021

We study the impact of conflict exposure on health in the Gaza Strip using individual‐level longitudinal data and geo‐localized information on conflict‐related violent events. Results show that individuals living in localities exposed to more conflict events have a higher probability of suffering from a physical impairment and a chronic disease. Two mechanisms contribute to explain why living in conflict‐affected area increases the incidence of physical impairment: conflict increases the difficulty to reach health facilities and it decreases individual income. The conflict‐induced increase in the probability of having high blood pressure is instead consistent with the development of Post‐Traumatic Stress Disorder (PTSD) due to the exposure to conflict‐related violent events.
Perioperative pain management and opioid‐reduction in head and neck endocrine surgery: An American Head and Neck Society Endocrine Surgery Section consensus statement
Authors: Ferrell Jay K. , Shindo Maisie L. , Stack Brendan C. , Angelos Peter , Bloom Gary , Chen Amy Y. , Davies Louise , Irish Jonathan C. , Kroeker Teresa , McCammon Susan D. , Meltzer Charles , Orloff Lisa A. , Panwar Aru , Shin Jennifer J. , Sinclair Catherine F. , Singer Michael C. , Wang Tiffany V. , Randolph Gregory W.
Published: June 2021

Background

This American Head and Neck Society (AHNS) consensus statement focuses on evidence‐based comprehensive pain management practices for thyroid and parathyroid surgery. Overutilization of opioids for postoperative pain management is a major contributing factor to the opioid addiction epidemic however evidence‐based guidelines for pain management after routine head and neck endocrine procedures are lacking.

Methods

An expert panel was convened from the membership of the AHNS, its Endocrine Surgical Section, and ThyCa. An extensive literature review was performed, and recommendations addressing several pain management subtopics were constructed based on best available evidence. A modified Delphi survey was then utilized to evaluate group consensus of these statements.

Conclusions

This expert consensus provides evidence‐based recommendations for effective postoperative pain management following head and neck endocrine procedures with a focus on limiting unnecessary use of opioid analgesics.
Linking minimal and detailed models of CA1 microcircuits reveals how theta rhythms emerge and their frequencies controlled
Authors: Chatzikalymniou Alexandra Pierri , Gumus Melisa , Skinner Frances K.
Published: June 2021

The wide variety of cell types and their biophysical complexities pose a challenge in our ability to understand oscillatory activities produced by cellular‐based computational network models. This challenge stems from their high‐dimensional and multiparametric natures. To overcome this, we implement a solution by linking minimal and detailed models of CA1 microcircuits that generate intrahippocampal (3–12 Hz) theta rhythms. We leverage insights from minimal models to guide explorations of more detailed models and obtain a cellular perspective of theta generation. Our findings distinguish the pyramidal cells as the theta rhythm initiators and reveal that their activity is regularized by the inhibitory cell populations, supporting a proposed hypothesis of an “inhibition‐based tuning” mechanism. We find a strong correlation between input current to the pyramidal cells and the resulting local field potential theta frequency, indicating that intrinsic pyramidal cell properties underpin network frequency characteristics. This work provides a cellular‐based foundation from which in vivo theta activities can be explored.
Efficacy of amisulpride for depressive symptoms in individuals with mental disorders: A systematic review and meta‐analysis
Authors: Zangani Caroline , Giordano Barbara , Stein Hans‐Christian , Bonora Stefano , D'Agostino Armando , Ostinelli Edoardo Giuseppe
Published: June 2021

Background

Depressive symptoms occur in several psychiatric disorders, often in the absence of a formal diagnosis of depression. We aimed to evaluate the efficacy and the tolerability of amisulpride, both alone and as augmentation therapy, in the treatment of depressive symptoms in individuals with any major psychiatric disorder.

Methods

We searched PubMed, Embase, PsycINFO, GreyLit, OpenGrey and ProQuest up to March 2020 for randomised controlled trials focussing on the treatment of an acute depressive episode in any major psychiatric disorder. A random‐effect meta‐analysis was performed to synthesize the findings on depressive symptoms (primary outcome), response rate and tolerability.

Results

We retrieved 11 studies including 2065 patients with a diagnosis of dysthymia (eight studies), major depression (one study) or schizophrenia (two studies). Amisulpride 50 mg/day was associated with a larger reduction of depressive symptoms compared to placebo (standardised mean difference [SMD] = −0.70, CI 95% −0.92, −0.49; I2 = 0.0%), and was found to be comparable to selective serotonin reuptake inhibitors (SSRIs; SMD = −0.08, CI 95% −0.23, 0.06, I2 = 0.0%), amineptine, imipramine and amitriptyline in the treatment of dysthymia (three studies, not pooled). In individuals with schizophrenia, amisulpride administered at higher doses (>400 mg/day) was comparable to olanzapine and risperidone (two studies, not pooled). In terms of tolerability, amisulpride was superior to placebo for dysthymia (odds ratio [OR] = 3.94, CI 95% 1.07, 14.48; I2 = 0.0) and comparable with SSRIs (OR = 0.94, CI 95% 0.55, 1.62; I2 = 0.0%).

Conclusion

Treatment with amisulpride could be a valid choice for selected individuals with dysthymia or depressive symptoms in the context of schizophrenia. More studies on the efficacy and tolerability of amisulpride are needed to draw firm conclusions on its potential benefits in other psychiatric disorders.
RIP3/MLKL pathway‐regulated necroptosis: A new mechanism of paclitaxel‐induced peripheral neuropathy
Authors: Ma Dongyang , Zhao Shuang , Liu Xin , Li Zhao , Li Huizhou , Liu Jiaxin , Cao Jing , Wang Xiuli
Published: June 2021

Paclitaxel (PTX) chemotherapy treatment often leads to neuropathic pain, which is resistant to available analgesic treatments. Death of cells and neuroinflammatory response are associated with PTX‐induced peripheral neuropathy (PIPN). Necroptosis is a form of regulated necrotic cell death that accompanies strong inflammatory response. It is mediated by receptor‐interacting protein kinase 3 (RIP3) and mixed‐lineage kinase domain‐like protein (MLKL), which contribute to the pathogenesis of several neurodegenerative diseases. Nevertheless, the role of necroptosis in PIPN remains unexplored. The aim of this study was to investigate the role of necroptosis in PIPN using its antagonists (necrostatin‐1 and Nec‐1). The quartic PTX administration (accumulated dose: 8 mg/kg, ip) in rats induced robust hyperalgesia and allodynia with significant cell necrosis and an increase in proinflammatory cytokines in the dorsal root ganglion (DRG). PTX application also increased RIP3 and MLKL protein levels in DRG, which were primarily in neurons. Moreover, it also promoted satellite glial cells (SGCs) activation, as assayed by glial fibrillary acidic protein (GFAP) upregulation. All these PTX‐induced changes were prevented by the Nec‐1 treatment. When taken together, the present study indicated that RIP3/MLKL pathway‐regulated neuronal necroptosis, which promoted an inflammatory cascade reaction in DRG, might be a new mechanism of PIPN.
More constructions for Sperner partition systems
Authors: Gowty Adam , Horsley Daniel
Published: June 2021

An ‐Sperner partition system is a set of partitions of some ‐set such that each partition has nonempty parts and no part in any partition is a subset of a part in a different partition. The maximum number of partitions in an ‐Sperner partition system is denoted . In this paper we introduce a new construction for Sperner partition systems based on a division of the ground set into many equal‐sized parts. We use this to asymptotically determine in many cases where is bounded as becomes large. Further, we show that this construction produces a Sperner partition system of maximum size for numerous small parameter sets . By extending a separate existing construction, we also establish the asymptotics of when for almost all odd values of .
The role of psychosocial factors in Black women's self‐efficacy in receiving genetic counseling and testing
Authors: Ding Huanghe , Sutton Arnethea L. , Hurtado‐de‐Mendoza Alejandra , Sheppard Vanessa B.
Published: June 2021

Higher self‐efficacy in receiving genetic counseling and testing (GCT) has been associated with greater participation in GCT for women at risk of hereditary breast and ovarian cancer (HBOC), but little is known about correlates of self‐efficacy in Black women eligible for GCT. The goal of this secondary analysis was to identify sociodemographic and psychosocial factors regarding GCT. Multivariable regression analysis was conducted to assess the relationship between self‐efficacy and correlates of interest. Of the 100 Black women surveyed, most women had a college degree (64%), were employed (84%), and had health insurance (93%). In the multivariable model, greater self‐efficacy was associated with more positive attitudes toward GCT (Β = 0.126; CI = 0.01 to 0.25; p = 0.039), greater confidence in the Genetic Information Nondiscrimination Act (GINA) (Β = 0.250; CI = 0.04 to 0.46; p = 0.019), and lower ratings of perceived difficulty obtaining GCT (Β = −0.219; CI = −0.46 to −0.10; p = 0.003). Community‐level interventions to promote self‐efficacy are needed that address perceived barriers to GCT, with the goals of increasing GINA Law awareness in the general public, increasing accessibility to genetic counseling (e.g., telemedicine), and promoting more positive attitudes about GCT.
Neutrophils vs. amoebas: Immunity against the protozoan parasiteEntamoeba histolytica
Authors: Rosales Carlos
Published: June 2021

Entamoeba histolytica is a protozoan parasite with high prevalence in developing countries, and causes amoebiasis. This disease affects the intestine and the liver, and is the third leading cause of human deaths among parasite infections. E. histolytica infection of the intestine or liver is associated with a strong inflammation characterized by a large number of infiltrating neutrophils. Consequently, several reports suggest that neutrophils play a protective role in amoebiasis. However, other reports indicate that amoebas making direct contact with neutrophils provoke lysis of these leukocytes, resulting in the release of their lytic enzymes, which in turn provoke tissue damage. Therefore, the role of neutrophils in this parasitic infection remains controversial. Neutrophils migrate from the circulation to sites of infection, where they display several antimicrobial functions, including phagocytosis, degranulation, and formation of neutrophil extracellular traps (NET). Recently, it was found that E. histolytica trophozoites are capable of inducing NET formation. Neutrophils in touch with amoebas launched NET in an explosive manner around the amoebas and completely covered them in nebulous DNA and cell aggregates where parasites got immobilized and killed. In addition, the phenotype of neutrophils can be modified by the microbiome resulting in protection against amoebas. This review describes the mechanisms of E. histolytica infection and discusses the novel view of how neutrophils are involved in innate immunity defense against amoebiasis. Also, the mechanisms on how the microbiome modulates neutrophil function are described.
Cyclovirus detection in Chilean adults with and without community‐acquired pneumonia
Authors: Prades Yara , Pizarro Rolando , Ruiz Mauricio , Moreno Cristian , Avendaño Luis F. , Luchsinger Vivian
Published: June 2021

Cycloviruses (CyV) (genus Cyclovirus, family Circoviridae) are nonenveloped DNA viruses. The first report in humans was in 2010 and research has focused only on disease‐associated human sample detection. The only HuACyV (CyCV‐ChileNPA1, HuACyV10) reported in the Chilean population was in children (3.3%) with an acute respiratory infection. Its detection in respiratory samples from adults, with/without respiratory disease remains unknown. The aim of this study was to detect HuACyV10 in adults with and without respiratory disease. HuACyV10 was studied in nasopharyngeal swabs from 105 hospitalized adults with community‐acquired pneumonia (CAP) and 104 adults without respiratory symptoms. Total nucleic acids were extracted, and viral rep and cp gene fragments were amplified by real‐time polymerase chain reaction. HuACyV10 was detected in 19.05% adults with CAP and in 0.96% asymptomatic adults, being significantly higher in adult CAP than asymptomatic (n = 1) ones (p = 0.0001). C
t values were between 26.7 and 39.6, and the median was 34.1 for rep and 33.8 for the CAP in adults CAP (p = 0.68), and 35.7 and 36.0, respectively, in the asymptomatic case. HuACyV10 detection in CAP adults concentrated in the Autumn–Winter season of the Southern hemisphere. The only asymptomatic adult with HuACyV10 was detected in the Spring–Summer period. In this first report of HuACyV10 in respiratory samples from adults, detection was significantly higher in CAP than in asymptomatic adults. As the sensitivity of both rep and cp genes was similar, both can be applied for detecting HuACyV10. It would be advisable to investigate the pathogenic role of HuACyV10 in adult respiratory infections.

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Efficient extra‐mitochondrial aerobic ATP synthesis in neuronal membrane systems
Authors: Ravera Silvia , Bartolucci Martina , Calzia Daniela , Morelli Alessandro M. , Panfoli Isabella
Published: June 2021

The nervous system displays high energy consumption, apparently not fulfilled by mitochondria, which are underrepresented therein. The oxidative phosphorylation (OxPhos) activity, a mitochondrial process that aerobically provides ATP, has also been reported also in the myelin sheath and the rod outer segment (OS) disks. Thus, commonalities and differences between the extra‐mitochondrial and mitochondrial aerobic metabolism were evaluated in bovine isolated myelin (IM), rod OS, and mitochondria‐enriched fractions (MIT). The subcellular fraction quality and the absence of contamination fractions have been estimated by western blot analysis. Oxygen consumption and ATP synthesis were stimulated by conventional (pyruvate + malate or succinate) and unconventional (NADH) substrates, observing that oxygen consumption and ATP synthesis by IM and rod OS are more efficient than by MIT, in the presence of both kinds of respiratory substrates. Mitochondria did not utilize NADH as a respiring substrate. When ATP synthesis by either sample was assayed in the presence of 10–100 µM ATP in the assay medium, only in IM and OS it was not inhibited, suggesting that the ATP exportation by the mitochondria is limited by extravesicular ATP concentration. Interestingly, IM and OS but not mitochondria appear able to synthesize ATP at a later time with respect to exposure to respiratory substrates, supporting the hypothesis that the proton gradient produced by the electron transport chain is buffered by membrane phospholipids. The putative transfer mode of the OxPhos molecular machinery from mitochondria to the extra‐mitochondrial structures is also discussed, opening new perspectives in the field of neurophysiology.
Resonance Raman spectroscopic analysis of the iron–sulfur cluster redox chain of the Ralstonia eutropha membrane‐bound [NiFe]‐hydrogenase
Authors: Siebert Elisabeth , Schmidt Andrea , Frielingsdorf Stefan , Kalms Jacqueline , Kuhlmann Uwe , Lenz Oliver , Scheerer Patrick , Zebger Ingo , Hildebrandt Peter
Published: June 2021

Iron–sulfur (Fe–S) centers are versatile building blocks in biological electron transfer chains because their redox potentials may cover a wide potential range depending on the type of the cluster and the specific protein environment. Resonance Raman (RR) spectroscopy is widely used to analyze structural properties of such cofactors, but it remains still a challenge to disentangle the overlapping signals of metalloproteins carrying several Fe–S centers. In this work, we combined RR spectroscopy with protein engineering and X‐ray crystallography to address this issue on the basis of the oxygen‐tolerant membrane‐bound hydrogenase from Ralstonia eutropha that catalyzes the reversible conversion of hydrogen into protons and electrons. Besides the NiFe‐active site, this enzyme harbors three different Fe–S clusters constituting an electron relay with a distal [4Fe–4S], a medial [3Fe–4S], and an unusual proximal [4Fe–3S] cluster that may carry a hydroxyl ligand in the superoxidized state. RR spectra were measured from protein crystals by varying the crystal orientation with respect to the electric field vector of the incident laser to achieve a preferential RR enhancement for individual Fe–S clusters. In addition to spectral discrimination by selective reduction of the proximal cluster, protein engineering allowed for transforming the proximal and medial cluster into standard cubane‐type [4Fe–4S] centers in the C19G/C120G and P242C variants, respectively. The latter variant was structurally characterized for the first time in this work. Altogether, the entirety of the RR data provided the basis for identifying the vibrational modes characteristic of the various cluster states in this “model” enzyme as a prerequisite for future studies of complex (FeS)‐based electron transfer chains.
Three‐dimensional printing‐based personalized limb salvage and reconstruction treatment of pelvic tumors
Authors: Wu Junxiang , Xie Kai , Luo Dinghao , Wang Lei , Wu Wen , Yan Mengning , Ai Songtao , Dai Kerong , Hao Yongqiang
Published: June 2021

Background and Objectives

The treatment of pelvic tumors is widely recognized to be challenging. The purpose of this study was to evaluate the efficacy of personalized three‐dimensional (3D) printing‐based limb salvage and reconstruction treatment for pelvic tumors.

Methods

Twenty‐eight pelvic tumor patients were enrolled. 3D printing lesion models and osteotomy templates were prepared for surgery planning, prosthesis design, and osteotomy assistance during surgery. 3D printing‐based personalized pelvic prostheses were manufactured and used in all 28 patients. Follow‐up of postoperative survival, prosthesis survival, imaging examinations, and Musculoskeletal Tumor Society (MSTS) lower limb functional scores were carried out.

Results

The mean follow‐up period was 32.2 months, during which 16 patients had disease‐free survival, 3 survived with the disease, and 9 died. The prostheses were stable, and the mean offset of the center of rotation was 5.48 mm. The prosthesis‐bone interface showed good integration. For the 19 surviving patients, the mean MSTS lower limb functional score was 23.2. Postoperative complications included superficial infection in six patients and hip dislocation in three patients.

Conclusions

Personalized 3D printing‐based limb salvage and reconstruction was an effective treatment for pelvic tumors. Our patients achieved good early postoperative efficacy and functional recovery.
Major modifications to minimize thoracic esophago‐gastric leak and eradicate esophageal stricture after Ivor Lewis esophagectomy
Authors: Housman Brian , Lee Dong‐Seok , Wolf Andrea , Nicastri Daniel , Kaufman Andrew , Rizk Nabil , Housman Arno , Song Kimberly , Hakami Ardeshir , Flores Raja M.
Published: June 2021

Background

The Ivor Lewis esophagectomy (ILE) remains the procedure of choice for localized middle or lower esophageal carcinoma. Nevertheless, anastomotic leak remains a common complication with rates from 3% to 25% and a stricture rate as high as 40%. The frequency of these complications suggests that the procedure itself may have inherent limitations including the use of potentially ischemic tissue for the esophagogastric anastomosis. We introduce a modified technique that reduces operative steps, preserves blood supply, and uses a modified esophagogastric anastomosis.

Methods

All consecutive patients undergoing ILE with the described modified technique were identified. An esophagram was performed on postoperative day six or seven. To ensure that all cases were identified, anastomotic leaks were defined as any radiographic evidence of contrast extravasation.

Results

A total of 110 patients underwent the modified esophagectomy with 2 anastomotic leaks (1.82%) and zero strictures. There was 1 late death but no early deaths (<30 or 90 days) or early re‐admissions (<30 days). The average number of risk factors was 2.12, and 98 patients (90%) had at least 1 risk factor in their medical history.

Conclusions

The modifications proposed simplify procedural steps, limit unnecessary dissection and introduce a technique that ends the practice of connecting ischemic tissue. We believe this technique contributes to surgical durability and reduces the rate of postoperative leak and eliminates stricture.
Obesity is not associated with disease‐free interval, melanoma‐specific survival, or overall survival in patients with clinical stage IB‐II melanoma after SLNB
Authors: Deckers Eric A. , Kruijff Schelto , Bastiaannet Esther , van Ginkel Robert J. , Hoekstra‐Weebers Josette E. H. M. , Hoekstra Harald J.
Published: June 2021

Background and Objectives

Clinicopathologic characteristics have prognostic value in clinical stage IB‐II patients with melanoma. Little is known about the prognostic value of obesity that has been associated with an increased risk for several cancer types and worsened prognosis after diagnosis. This study aims to examine effects of obesity on outcome in patients with clinical stage IB‐II melanoma.

Methods

Prospectively recorded data of patients with clinical stage IB‐II melanoma who underwent sentinel lymph node biopsy (SLNB) between 1995 and 2018 at the University Medical Center of Groningen were collected from medical files and retrospectively analyzed. Cox‐regression analyses were used to determine associations between obesity (body mass index> 30), tumor (location, histology, Breslow‐thickness, ulceration, mitotic rate, SLN‐status) and patient‐related variables (gender, age, and social‐economic‐status [SES]) and disease‐free interval (DFI), melanoma‐specific survival (MSS), and overall survival (OS).

Results

Of the 715 patients, 355 (49.7%) were women, median age was 55 (range 18.6‐89) years, 149 (20.8%) were obese. Obesity did not significantly affect DFI (adjusted hazard ratio [HR] = 1.40; 95% confidence interval [CI] = 0.98–2.00; p = 0.06), MSS (adjusted HR = 1.48;95%CI = 0.97–2.25; p = 0.07), and OS (adjusted HR = 1.25; 95% CI = 0.85–1.85; p = 0.25). Increased age, arm location, increased Breslow‐thickness, ulceration, increased mitotic rate, and positive SLN‐status were significantly associated with decreased DFI, MSS, and OS. Histology, sex, and SES were not associated.

Conclusion

Obesity was not associated with DFI, MSS, or OS in patients with clinical stage IB‐II melanoma who underwent SLNB.
The prognostic impact of resection margin status varies according to the genetic and morphological evaluation (GAME) score for colorectal liver metastasis
Authors: Wang Hong‐Wei , Wang Li‐Jun , Jin Ke‐Min , Bao Quan , Li Juan , Wang Kun , Xing Bao‐Cai
Published: June 2021

Background

Surgical margin status remains a controversial factor in predicting the outcome of colorectal liver metastases (CRLM) resection. Our study aims to evaluate the effects of surgical margins on oncologic outcomes with regard to the genetic and morphological evaluation (GAME) score.

Methods

R1 resection was defined as having a less than 1 mm margin width. Patients who underwent surgery for CRLM from January 2005 to December 2018 were recruited. The patients were divided into two risk subgroups, namely, the low or medium risk (GAME 0–3) and high‐risk (GAME score 4 or more) groups. The effects of margin status on overall survival (OS) and recurrence‐free survival rate (RFS) were examined.

Results

In total, 661 patients were recruited, among which 159 (24.1%) had R1 resection. Before hepatectomy, 514 patients showed a low or medium risk (R1 resection: n = 124), while 147 patients demonstrated a high risk (R1 resection: n = 35). In the whole cohort, multivariable analysis did show that R1 resection was associated with worse RFS and OS. While further research only found that in the low or medium risk group, R1 resection was related to poor OS and RFS. Meanwhile, in the high risk group, no significant difference was found in the median OS and RFS among patients with R0 or R1 resection.

Conclusion

The prognostic role of margin status varied according to the GAME score. Margin clearance only improved survival rates in patients with low or medium GAME score. In contrast, R1 resection demonstrated similar oncologic outcomes with R0 resection in patients with high GAME score.
Development of a standardized histopathology scoring system for intervertebral disc degeneration and regeneration in rabbit models‐An initiative of the ORSspine section
Authors: Gullbrand Sarah E. , Ashinsky Beth G. , Lai Alon , Gansau Jennifer , Crowley James , Cunha Carla , Engiles Julie B. , Fusellier Marion , Muehleman Carol , Pelletier Matthew , Presciutti Steven , Schol Jordy , Takeoka Yoshiki , Yurube Takashi , Zhang Yejia , Masuda Koichi , Iatridis James C.
Published: June 2021

Background

The rabbit lumbar spine is a commonly utilized model for studying intervertebral disc degeneration and for the pre‐clinical evaluation of regenerative therapies. Histopathology is the foundation for which alterations to disc morphology and cellularity with degeneration, or following repair or treatment are assessed. Despite this, no standardized histology grading scale has yet been established for the spine field for any of the frequently utilized animal models.

Aims

The purpose of this study was to establish a new standardized scoring system to assess disc degeneration and regeneration in the rabbit model.

Materials and Methods

The scoring system was formulated following a review of the literature and a survey of spine researchers. Validation of the scoring system was carried out using images provided by 4 independent laboratories, which were graded by 12 independent graders of varying experience levels. Reliability testing was performed via the computation of intra‐class correlation coefficients (ICC) for each category and the total score. The scoring system was then further refined based on the results of the ICC analysis and discussions amongst the authors.

Results

The final general scoring system involves scoring 7 features (nucleus pulposus shape, area, cellularity and matrix condensation, annulus fibrosus/nucleus pulposus border appearance, annulus fibrosus morphology, and endplate sclerosis/thickening) on a 0 (healthy) to 2 (severe degeneration) scale. ICCs demonstrated overall moderate to good agreement across graders. An addendum to the main scoring system is also included for use in studies evaluating regenerative therapeutics, which involves scoring cell cloning and morphology within the nucleus pulposus and inner annulus fibrosus.

Discussion

Overall, this new scoring system provides an avenue to improve standardization, allow a more accurate comparison between labs and more robust evaluation of pathophysiology and regenerative treatments across the field.

Conclusion

This study developed a histopathology scoring system for degeneration and regeneration in the rabbit model based on reported practice in the literature, a survey of spine researchers, and validation testing.
Determination of eight endocrine disruptor pesticides in bovine milk at trace levels by dispersive liquid‐liquid microextraction followed by GC‐MS determination
Authors: Sharma Nisha , Thakur Pragati , Chaskar Manohar G.
Published: June 2021

Endocrine disrupting chemicals are chemicals that interfere with any aspect of the endocrine system. Several natural and synthetic chemicals, including pesticides, have been identified as endocrine disruptors, which potentially inhibit the reproductive activity of the hormonal system. The pervasive occurrence with trace level concentrations and extensive variety are the reported characteristics of these chemicals.

In this study, a dispersive liquid‐liquid microextraction method coupled with gas chromatography and mass spectrometry for the determination of eight potential endocrine disruptor pesticides (Lindane, Diazinon, Fenitrothion, Malathion, Aldrin, α‐Endosulfan, β‐Endosulfan, Methoxychlor) in bovine milk samples was developed. Several parameters that can influence the extraction efficiency were studied. Under optimized conditions, the calibration curves of all eight analytes presented coefficient of determination higher than 0.998 (range level of 2.0‐1000 ng/mL). The limits of detection and quantification ranged from 0.90 to 5.00 ng/mL and 2.50 to 15.0 ng/mL, respectively.
Correlation of alterations in the KEAP1/CUL3/NFE2L2 pathway with radiation failure in larynx squamous cell carcinoma
Authors: Sheth Siddharth , Farquhar Douglas R. , Schrank Travis P. , Stepp Wesley , Mazul Angela , Hayward Michele , Lenze Nicholas , Little Paul , Jo Heejoon , Major M. Ben , Chera Bhishamjit S. , Zevallos Jose P. , Hayes D. Neil
Published: June 2021

Objectives

Patients with laryngeal squamous cell carcinoma (LSCC) often fail radiation therapy (RT), when received as monotherapy or in combination with other treatment modalities. Mechanisms for RT failure are poorly understood. We hypothesized that tumors failing RT would have increased rates of somatic mutations in genes associated with radiation resistance, particularly in genes associated with the NFE2L2 oxidative stress pathway. Using targeted exome sequencing on pretreated LSCC tumors, we retrospectively compared somatic mutation profile with clinical data and response to treatment.

Methods

Tumors were classified as either radiation‐resistant (RR) or radiation‐sensitive (RS). RR was defined as persistent or recurrent disease within 2 years of receiving full‐dose RT. Early stage (ES) LSCC was defined as Stage I or II tumors without lymph node involvement. Eight genes associated with radiation resistance were prioritized for analysis. RT‐qPCR was performed on five NFE2L2 pathway genes.

Results

Twenty LSCC tumors were included and classified as either RR (n = 8) or RS (n = 12). No differences in individual rates of somatic mutations by genes associated with radiation resistance were identified. Higher rates of total mutational burden (TMB) and increased alterations associated with the NFE2L2 pathway was observed in RR vs RS tumors (P < .05). In an analysis of only ES‐LSCC patients (RR, n = 3 and RS, n = 3), RR tumors had increased NFE2L2 somatic pathway mutations (P = .014) and increased NQO1 mRNA expression (P = .05).

Conclusion

Increased TMB and NFE2L2 pathway alterations were associated with radiation resistance in LSCC. NQO1 mRNA expression may serve as a biomarker for RT response in ES‐LSCC.

Level of Evidence: II1.
Donor Morbidity Is Equivalent Between Right and Left Hepatectomy for Living Liver Donation: A Meta‐Analysis
Authors: Vargas Paola A. , McCracken Emily K.E. , Mallawaarachchi Indika , Ratcliffe Sarah J. , Argo Curtis , Pelletier Shawn , Zaydfudim Victor M. , Oberholzer Jose , Goldaracena Nicolas
Published: June 2021

Maximizing liver graft volume benefits the living donor liver recipient. Whether maximizing graft volume negatively impacts living donor recovery and outcomes remains controversial. Patient randomization between right and left hepatectomy has not been possible due to anatomic constraints; however, a number of published, nonrandomized observational studies summarize donor outcomes between 2 anatomic living donor hepatectomies. This meta‐analysis compares donor‐specific outcomes after right versus left living donor hepatectomy. Systematic searches were performed via PubMed, Cochrane, ResearchGate, and Google Scholar databases to identify relevant studies between January 2005 and November 2019. The primary outcomes compared overall morbidity and incidence of severe complications (Clavien‐Dindo >III) between right and left hepatectomy in donors after liver donation. Random effects meta‐analysis was performed to derive summary risk estimates of outcomes. A total of 33 studies (3 prospective and 30 retrospective cohort) were used to identify 7649 pooled patients (5993 right hepatectomy and 1027 left hepatectomy). Proportion of donors who developed postoperative complications did not significantly differ after right hepatectomy (0.33; 95% confidence interval [CI], 0.27‐0.40) and left hepatectomy (0.23; 95% CI, 0.17‐0.29; P = 0.19). The overall risk ratio (RR) did not differ between right and left hepatectomy (RR, 1.16; 95% CI, 0.83‐1.63; P = 0.36). The relative risk for a donor to develop severe complications showed no differences by hepatectomy side (Incidence rate ratio, 0.97; 95% CI, 0.67‐1.40; P = 0.86). There is no evidence that the overall morbidity differs between right and left lobe donors. Publication bias reflects institutional and surgeon variation. A prospective, standardized, multi‐institutional study would help quantify the burden of donor complications after liver donation.