bluuebunny/crossref_metadata_2025 huggingface dataset:
High‐risk group of upper and middle mediastinal lymph node metastasis in patients with esophagogastric junction carcinoma
Authors: Yura Masahiro , Takeuchi Hiroya , Fukuda Kazumasa , Nakamura Rieko , Suda Koichi , Wada Norihito , Kawakubo Hirofumi , Kitagawa Yuko
Published: October 2018

Aim

The aim of the present study was to clarify esophagogastric junction (EGJ) carcinoma patients who are at high risk of upper and middle mediastinal lymph node (MLN) metastasis.

Methods

This was a retrospective study and included 110 consecutive patients with EGJ carcinoma who underwent R0/R1 resection at Keio University Hospital between January 2000 and December 2013.

Results

Of the 110 patients, 18 (16.3%) had MLN metastasis, and the number increased to 23 (20.9%) when recurrence cases were added (adenocarcinoma, N = 11; squamous cell carcinoma, N = 12). Patients whose tumor epicenter was located above the EGJ had a significantly higher incidence of MLN metastasis/recurrence (18/51 [35.3%]) than those whose tumor epicenter was located below the EGJ (5/59 [8.5%]). The MLN metastasis/recurrence rate was particularly high when the distance from the EGJ to the proximal edge of the primary tumor was >3 cm for the upper and middle mediastinum (18.8%). Patients in a selected group (≥T2 and tumor epicenter located above the EGJ or below the EGJ with ≥3 cm esophageal invasion) showed 17.9% and 15.4% upper and middle MLN metastasis/recurrence rates, respectively. Therapeutic value of MLN dissection was relatively high (#105 + 106: 8.9, #110: 12.2).

Conclusions

Therapeutic value of MLN dissection to treat EGJ carcinomas was relatively high in patients with MLN metastasis. Our algorithm could select patients at high risk for MLN metastasis.
Impact of T‐cell depletion strategies on outcomes following hematopoietic stem cell transplantation for idiopathic aplastic anemia: A study on behalf of the European blood and marrow transplant severe aplastic anemia working party
Authors: Samarasinghe Sujith , Clesham Katherine , Iacobelli Simona , Sbianchi Giulia , Knol Cora , Hamladji Rose‐Marie , Socié Gerard , Aljurf Mahmoud , Koh Mickey , Sengeloev Henrik , Dalle Jean‐Hugues , Robinson Stephen , Van Lint Maria Teresa , Halkes Constantijn J. M. , Beelen Dietrich , Mufti Ghulam J. , Snowden John , Blaise Didier , de Latour Regis Peffault , Marsh Judith , Dufour Carlo , Risitano Antonio M ,   Severe Aplastic Anaemia Working Party of the EBMT
Published: October 2018

We retrospectively analyzed the outcomes of 1837 adults and children with severe aplastic anemia (SAA) who underwent matched sibling donor (MSD) and matched unrelated donor (MUD) hemopoietic stem cell transplantation (HSCT) between 2000 and 2013. Patients were grouped by transplant conditioning containing either anti‐thymocyte globulin (ATG) (n = 1283), alemtuzumab (n = 261), or no serotherapy (NS) (n = 293). The risks of chronic GvHD were significantly reduced when ATG or alemtuzumab were compared with NS (P = .021 and .003, respectively). Acute GVHD was significantly reduced in favor of alemtuzumab compared with ATG (P = .012) and NS (P < .001). By multivariate analysis, when compared with ATG, alemtuzumab was associated with a lower risk of developing acute (OR 0.262; 95% CI 0.14‐0.47; P < .001) and chronic GVHD (HR 0.58; 95% CI 0.35‐0.94; P = .027). OS was significantly better in ATG and alemtuzumab patients compared with NS (P = .010 and .025). Our data shows inclusion of serotherapy in MSD and MUD HSCT for patients with SAA reduces chronic GVHD and provides a survival advantage over patients not receiving serotherapy. Notably, alemtuzumab reduced the risk of acute and chronic GvHD compared with ATG and indicates that alemtuzumab might be the serotherapy of choice for MSD and MUD transplants for SAA.
Duplicated distal phalanx of thumb or hallux in trisomy 13: A recurrent feature in a series of 42 fetuses
Authors: Létard Pascaline , Guimiot Fabien , Dupont Céline , Rosenblatt Jonathan , Delezoide Anne‐Lise , Khung‐Savatovsky Suonavy
Published: October 2018

Trisomy 13 or Patau syndrome (PS) is a well‐known aneuploidy characterized by a polymalformative syndrome. We described a large series of fetuses with PS and compared them with cases described in the literature, most of which were live‐born. In all, 42 fetuses, aged from 14 to 41 gestational weeks (GW), were examined. The main defects observed were similar to those described in live‐born patients: congenital heart defects (76%), holoprosencephaly spectrum anomalies including arhinencephaly and hypotelorism (74%), urinary tract anomalies (71%), ear anomalies (69%), postaxial polydactyly (67%), anogenital anomalies (60%), anophthalmos, and/or microphthalmos (53%), brachycephaly (45%), and oro‐facial clefts (45%). A duplication or triplication of at least one distal phalanx of the thumb or hallux was present in 38% of fetuses. This sign has only been reported previously in one patient in the literature. Fetal examination in trisomy 13, is thus, useful to complete the phenotype or to orient diagnosis toward trisomy 13 in the absence of cytogenetic analysis.
Sound Generating Structures of the Humpback Dolphin Sousa plumbea (Cuvier, 1829) and the Directionality in Dolphin Sounds
Authors: Frainer Guilherme , Plön Stephanie , Serpa Nathalia B. , Moreno Ignacio B. , Huggenberger Stefan
Published: October 2018

The macroscopic morphology of structures involved in sound generation in the Indian Ocean humpback dolphin (Sousa plumbea) were described for the first time using computed tomography imaging and standard gross dissection techniques. The Indian Ocean humpback dolphin may represent a useful comparative model to the bottlenose dolphin (Tursiops sp.) to provide insights into the functional anatomy of the sound production in dolphins, since these coastal dolphins exhibit similar body size and share similarities on acoustic behavior. The general arrangement of sound generating structures, that is, air sacs and muscles, was similar in both the bottlenose dolphin and the Indian Ocean humpback dolphin. The main difference between the two species existed in a small left posterior branch of the melon in the Indian Ocean humpback dolphin, which was not found in the bottlenose dolphin and might reflect an adaptation of directionality for high frequency communication sounds as seen in some other delphinids (e.g., Lagenorhynchus sp., Grampus griseus). Thus, this may be the main reason for the asymmetry of the sound production structures in dolphins. Additionally, the longer rostrum in Indian Ocean humpback dolphins might suggest a more directional echolocation beam compared to the Lahille's bottlenose dolphin. Anat Rec, 302:849–860, 2019. © 2018 Wiley Periodicals, Inc.
5‐Hydroxytryptamine and Dopamine Neurons in the Cerebellum of the New‐Hatching Yangtze AlligatorAlligator sinensis
Authors: Ren Shijia , Chen Meifang , Yang Lanying , Liu Zaiqun
Published: October 2018

Nissl and immunohistochemical staining methods were used to morphologically characterize the cerebellum of the new‐hatching Yangtze alligator, and the cerebellar histological structure and the distribution profiles of 5‐hydroxytryptamine (5‐HT) and dopamine (DA) neurons were investigated for the first time. The results of cerebellar histological structure showed that there was a ventriculus cerebelli in the cerebellum of the new‐hatching Yangtze alligator, the surface of the cerebellar cortex was not very smooth, the cerebellar cortex could be divided into four layers, which include external granular layer, molecular layer, Purkinje cell layer and granular layer, Purkinje cell layer could be characterized specially by multilayer, two cerebellar nuclei termed as the nucleus cerebelli lateralis and the nucleus cerebelli medialis were found in the cerebellar medulla. 5‐hydroxytryptamine‐immunoreactive (5‐HT‐IR) and dopamine‐immunoreactive (DA‐IR) neurons and fibers distributed widely in the cerebellum. The structures and profiles of 5‐HT‐IR and DA‐IR neurons and fibers in the cerebellum of the Yangtze alligator were similar to that reported in other reptiles, but also had some specific features. The abundance of 5‐HT and DA in cerebellum suggested that these highly conserved neurotransmitters would play important roles in motor control. Anat Rec, 302:861–868, 2019. © 2018 Wiley Periodicals, Inc.
Good Vibrations: The Evolution of Whisking in Small Mammals
Authors: Muchlinski Magdalena N. , Wible John R. , Corfe Ian , Sullivan Matthew , Grant Robyn A.
Published: October 2018

While most mammals have whiskers, some tactile specialists—mainly small, nocturnal, and arboreal species—can actively move their whiskers in a symmetrical, cyclic movement called whisking. Whisking enables mammals to rapidly, tactually scan their environment to efficiently guide locomotion and foraging in complex habitats. The muscle architecture that enables whisking is preserved from marsupials to primates, prompting researchers to suggest that a common ancestor might have had moveable whiskers. Studying the evolution of whisker touch sensing is difficult, and we suggest that measuring an aspect of skull morphology that correlates with whisking would enable comparisons between extinct and extant mammals. We find that whisking mammals have larger infraorbital foramen (IOF) areas, which indicates larger infraorbital nerves and an increase in sensory acuity. While this relationship is quite variable and IOF area cannot be used to solely predict the presence of whisking, whisking mammals all have large IOF areas. Generally, this pattern holds true regardless of an animal's substrate preferences or activity patterns. Data from fossil mammals and ancestral character state reconstruction and tracing techniques for extant mammals suggest that whisking is not the ancestral state for therian mammals. Instead, whisking appears to have evolved independently as many as seven times across the clades Marsupialia, Afrosoricida, Eulipotyphla, and Rodentia, with Xenarthra the only placental superordinal clade lacking whisking species. However, the term whisking only captures symmetrical and rhythmic movements of the whiskers, rather than all possible whisker movements, and early mammals may still have had moveable whiskers. Anat Rec, 2018. © 2018 American Association for Anatomy.
Swing‐Stabilization Up for a Rotatory‐Elastic Pendulum Via Nonlinear Sub‐Optimal Control
Authors: Sánchez Bonifacio , Ordaz Patricio , Santos Omar
Published: October 2018

This paper deals with the smooth control design for Swing‐Stabilization Up of underactuated pendular robot. The considered system has, at least, two different no actuated links, one of them is pendular like elbow, the other one is prismatic and elastic. Thus, the control aim is to swing‐up and stabilize the underactuated system by using non‐switched control algorithm. To this, the control algorithm summarizes the concept of sub‐optimal control, the energy based control and the Kalman's canonical decomposition to unify the Swing‐Up and Stabilization of the considered underactuated system. In order to test the designed control algorithm, experimental results are presented for the non‐conventional rotatory elastic‐pendulum system.
Congenital heart disease complexity and childhood cancer risk
Authors: Collins R. Thomas , Von Behren Julie , Yang Wei , Carmichael Suzan L. , Reynolds Peggy , Fisher Paul G. , Shaw Gary M.
Published: October 2018

Background

Childhood cancer is increased in those with birth defects, including those with congenital heart disease (CHD). Lymphoma risk is increased in children with CHD. This study analyzes the effect of CHD and CHD severity on childhood cancer risk.

Methods

We analyzed cancer risk in a population‐based cohort of children with and without CHD born between 1988 and 2004 by linking data from the California Birth Defects Monitoring Program with data from the California Cancer Registry. We compared cancer risk in children with and without CHD, excluding children with chromosomal anomalies.

Results

Of >3 million children in the birth cohort, 65,585 had birth defects (2%), 25,981 with CHD. Cancer occurred in 4,781 (0.15%) children, 43 (0.17%) with CHD. Cancer risk in CHD was increased (hazard ratio [HR]) 2.63, 95% CI: 1.95, 3.55). Leukemia was the most common cancer in those without CHD (1,722/4,738, 36%), central nervous system tumors were second (1,073/4,738, 23%), and lymphoma third (410/4,738, 9%). Among children with CHD, lymphoma and leukemia occurred with the same frequency (12/43, 28% for each). HR for lymphoma was 8.37 (CI: 4.71, 14.86) with CHD versus without. HR for leukemia was 2.05 (CI: 1.16, 3.61) with CHD versus without. CHD complexity was higher in lymphoma (3, interquartile range [IQR]: 2–3) than those with leukemia (1, IQR, 1–2; p < .02).

Conclusion

Cancer risk is increased in children with CHD. Lymphoma risk is increased in CHD and is correlated with more complex CHD. These results suggest a shared developmental origin for CHD and lymphoma may be present.
My Favorite Animal, Amphioxus: Unparalleled for Studying Early Vertebrate Evolution
Authors: Escriva Hector
Published: October 2018

Amphioxus represents the most basally divergent group in chordates and probably the best extant proxy to the ancestor of all chordates including vertebrates. The amphioxus, or lancelets, are benthic filter feeding marine animals and their interest as a model in research is due to their phylogenetic position and their anatomical and genetic stasis throughout their evolutionary history. From the first works in the 19th century to the present day, enormous progress is made mainly favored by technical development at different levels, from spawning induction and husbandry techniques, through techniques for studies of gene function or of the role of different signalling pathways through embryonic development, to functional genomics techniques. Together, these advances foretell a plethora of interesting developments in the world of research with the amphioxus model. Here, the discovery and development of amphioxus as a superb model organism in evolutionary and evolutionary‐developmental biology are reviewed.
The self‐reduction synthesis and luminescent properties of Eu2+/Eu3+ activated BaZrxSi3O7+2x phosphors with white light emission for white light‐emitting diodes
Authors: Zhong Jianlin , Yu Lixin , Man Xiaoqin , Sun Wei , Wu Xiao , Jiang Xiaofang , Gao Zhengyu , Guo Qihuang , Zou Yingxuan
Published: October 2018

The BaZrxSi3O7+2x:Eu2+/Eu3+ (2%, molar ratio) phosphors were prepared with adding different amounts of zirconium dioxide (ZrO2) (x = 0, 0.2, 0.4, 0.6, 0.8, and 1) by a self‐reduction method under air conditions. X‐ray diffraction, photoluminescence properties, thermal quenching properties and luminescent lifetimes of the prepared samples were systematically analyzed. In BaZrxSi3O7+2x:Eu2+/Eu3+, both the 4f → 5d transitions of Eu2+ and sharp emissions assigned to 5D0 → 7FJ (J = 0, 1, 2, 3, 4) transitions of Eu3+ were observed. In addition, the results also reveal that the amount of ZrO2 affects the crystal structure, the self‐reduction process and further influences the relative intensity of Eu2+/Eu3+ in all samples. Therefore, the diverse emission colors can be obtained and modulated by controlling the content of ZrO2. The highlight of this work is that the white light emission is observed, when x is 0.4, 0.6, 0.8 and 1, respectively.
The anatomical relationship between the sural nerve and small saphenous vein: An ultrasound study of healthy participants
Authors: Garagozlo Cameron , Kadri Omar , Atalla Mina , Polanco Fernando , Massaband Andrew , Coey James , Sulaiman Sara
Published: October 2018

Procedures involving the small saphenous vein (SSV) can result in sural nerve (SN) damage due to the proximity of the two structures. The relationship between the SN and SSV has previously been described in cadaveric studies with limited scope on surface landmarks. This study investigates the relationship between the SN and SSV in vivo through ultrasound. Transverse/short‐axis ultrasound scans of 128 legs (64 healthy participants) were taken by a single observer using a GE Logiq e ultrasound system with a 5–13 Hz linear transducer (GE Logiq 12L‐RS). The SN was identified and traced from the lateral malleolus to the popliteal fossa noting its course and proximity to the SSV. The distance between the SN and SSV was measured at points representing the distal 50% and 25% of the total leg length (the distance between the medial tibial condyle and the inferior edge of the medial malleolus). The SN and SSV were visualized in all participants regardless of BMI and atypical anatomical relationship were noted in 20.3%. The SN pierced the fascia in the distal 25.9% ± 5.3% of the total leg length. The distance between the SN and SSV was 4.06 ± 1.8 mm and 3.4 ± 1.4 mm in the distal 50% and 25% points of the total leg length, respectively. There was no significant effect of sex or body side. The SSV is a viable option for multiple vein harvest. Ultrasound visualization can be a beneficial tool for delineating variations of the SN in relation to SSV prior to surgery. Clin. Anat. 32:277–281, 2019. © 2018 Wiley Periodicals, Inc.
Fabrication of Stable and Well‐connected Proton Path in Catalyst Layer for High Temperature Polymer Electrolyte Fuel Cells
Authors: Luo Fang , Zhang Quan , Yang Zehui , Guo Long , Yu Xinxin , Qu Konggang , Ling Ying , Yang Jun , Cai Weiwei
Published: October 2018

It is of importance to establish stable and well‐connected proton path in the catalyst layer to promote the fuel cell performance. Here, we describe a novel method to fabricate stable and efficient proton path for high temperature polymer electrolyte fuel cells (HT‐PEFCs), in which the ionic liquid is doped into the platinum electrocatalyst. The electrochemical results depict that ionic liquid doped electrocatalyst exhibits comparable electrochemical surface area (ESA) and enhanced durability indicating that ionic liquid negligibly affects the hydrogen adsorption/desorption process and protects the electrocatalyst from carbon corrosion. Interestingly, the catalyzing activity toward oxygen reduction reaction (ORR) of Pt electrocatalyst is boosted after doping with ionic liquid mainly due to the modified electronic structures of Pt atoms induced by nitrogen atoms from ionic liquid resulting in weak interaction between Pt atoms and intermediates. The fuel cell performance of ionic liquid doped electrocatalyst is much improved ascribed to the homogeneously dispersed ionic liquid on the surface of Pt electrocatalyst facilitating the fabrication of triple phase boundaries (TPBs) as a result of efficient proton conduction in the catalyst layer. The fuel cell performance only decreases 10 % after 100,000 potential cycles from 1.0 to 1.5 V versus RHE suggesting that ionic liquid forms a stable proton path in the catalyst layer. Thus, the ionic liquid doped Pt electrocatalyst is applicable for the real HT‐PEFC operation.
Recent Advances in Methylation: A Guide for Selecting Methylation Reagents
Authors: Chen Yantao
Published: October 2018

Methylation is a well‐known structural modification in organic and medicinal chemistry. This review summarizes recent advances in methylation by categorizing specific methylation reagents. The challenges of mono N‐methylation of aliphatic amines and N‐methylation of peptides are discussed. This review will be useful for chemists wanting to select the appropriate reagents for methylation chemistry. Based on the large diversity of methylation reagents and their wide scope, this review also broadens perspectives on which strategies to select for utilizing a particular methylation, resulting in an increased flexibility in synthetic route planning.
Recent Progress in Fluorescence Signal Design for DNA‐Based Logic Circuits
Authors: Yang Shu , Yang Chunrong , Huang Dan , Song Lingbo , Chen Jianchi , Yang Qianfan
Published: October 2018

DNA‐based logic circuits, encoding algorithms in DNA and processing information, are pushing the frontiers of molecular computers forward, owing to DNA′s advantages of stability, accessibility, manipulability, and especially inherent biological significance and potential medical application. In recent years, numerous logic functions, from arithmetic to nonarithmetic, have been realized based on DNA. However, DNA can barely provide a detectable signal by itself, so that the DNA‐based circuits depend on extrinsic signal actuators. The signal strategy of carrying out a response is becoming one of the design focuses in DNA‐based logic circuit construction. Although work on sequence and structure design for DNA‐based circuits has been well reviewed, the strategy on signal production lacks comprehensive summary. In this review, we focused on the latest designs of fluorescent output for DNA‐based logic circuits. Several basic strategies are summarized and a few designs for developing multi‐output systems are provided. Finally, some current difficulties and possible opportunities were also discussed.
Synthesis of Diverse α‐Fluoroalkoxyaryl Derivatives and Their Use for the Generation of Fluorinated Macrocycles
Authors: Cogswell Thomas J. , Dahlén Anders , Knerr Laurent
Published: October 2018

Introduction of difluorinated functionality has emerged as a powerful means for conformational design with minimal steric footprint. Synthetic approaches for the preparation of aryl difluoromethylene ether containing novel building blocks were established, enabling the inclusion of the aryl difluoromethylene ether system into macrocyclic scaffolds for the first time.
The small molecule AMBMP disrupts microtubule growth, ciliogenesis, cell polarity, and cell migration
Authors: Werner Michael , del Castillo Urko , Ventrella Rosa , Brotslaw Eva , Mitchell Brian
Published: October 2018

2‐Amino‐4‐(3,4‐[methylenedioxy]benzylamino)‐6‐(3‐methoxyphenyl)pyrimidine (AMBMP) is a small molecule that has been previously reported to be both a Wnt agonist and a microtubule (MT) regulator. Here we report a detailed analysis of AMBMPs effects on MTs and on MT associated cellular processes including cell polarity, ciliogenesis, and cell migration. Specifically, treatment of Xenopus embryos with AMBMP leads to defects similar to the MT depolymerizing drug nocodazole, including a failure to generate or polarize cilia (depending on the timing of treatment) and a loss of the cell movements associated with radial intercalation. The dramatic effect AMBMP has on basic MT based cellular functions suggests that its usefulness as a Wnt regulator is questionable. Moreover, it may be an important new tool for experimental or pharmacological manipulation of MTs.
Depiction of the perfusion components’ volume fraction distribution in generalized intravoxel incoherent motion by using Gaussian mixture model
Authors: Wang Shunli , Liu Wanyu , Kuai Zixiang , Zhu Yuemin
Published: October 2018

Gaussian mixture model (GMM) was proposed to depict the perfusion volume fraction distribution in the generalized intravoxel incoherent motion model (GIVIM) to improve GIVIM's ability of describing complex perfusion conditions and their changes. Different hepatic perfusion conditions were accounted for by performing different combinations of imaging sequence and diffusion time on six normal livers. In order to evaluate GIVIM‐GMM's reliability in perfusion condition analysis, the fitting to diffusion‐weighted (DW) data and the consistency between diffusion‐related parameters’ change and the data's change were tested and the recent GIVIM and the triexponential models were chosen for comparison. The difference of the fitting results was evaluated by performing the extra‐sum‐of‐squares F test and information criteria on normal human DW data. The difference of the consistency was assessed by using two‐tailed paired Student's t test. In the extra‐sum‐of‐squares F test, the relative difference ratio F values derived from the GIVIM and GIVIM‐GMM and that derived from the triexponential model and the GIVIM‐GMM are respectively 25.334 and 27.976, which indicates that significant difference existed and that the GIVIM‐GMM provides better fit to the normal human liver DW data. In information criteria test, the evidence ratio values were determined by dividing the GIVIM's or triexponential model's correct probability by the GIVIM‐GMM's. Both evidence ratio values (2.3942 × 10−10, 8.6167 × 10−9, respectively) are much smaller than 1, which also expresses that the best model used to fit the normal human liver DW data was the GIVIM‐GMM. In two‐tailed paired student's t test, the GIVIM‐GMM provides more parameters to give a finer description of perfusion than the triexponential model or GIVIM. In short, all the results demonstrated that the GIVIM‐GMM provides better performance than the existing IVIM models for depicting the signal attenuation in DW imaging.
Survival of patients with head and neck cancer treated with definitive radiotherapy and concurrent cisplatin or concurrent cetuximab: A Surveillance, Epidemiology, and End Results‐Medicare analysis
Authors: Xiang Michael , Holsinger F. Christopher , Colevas A. Dimitrios , Chen Michelle M. , Le Quynh‐Thu , Beadle Beth M.
Published: October 2018

Background

Cisplatin and cetuximab are both systemic therapies commonly used in combination with radiation (RT) for the definitive treatment of head and neck cancers, but their comparative efficacy is unclear.

Methods

Patients with locoregionally advanced (American Joint Committee on Cancer stage III‐IVB) squamous cell carcinomas of the oropharynx, larynx, or hypopharynx were identified in the Surveillance, Epidemiology, and End Results‐Medicare database. Patients received either cisplatin or cetuximab concurrent with RT, as determined by Medicare claims. The primary study outcome was head and neck cancer‐specific mortality (CSM) analyzed with competing risks. Filtering, propensity score matching, and multivariable Fine‐Gray regression were used to adjust for differences between the cisplatin and cetuximab cohorts, including age, comorbidity, and cycles of systemic therapy received.

Results

The total cohort consisted of 1395 patients, of whom 786 (56%) received cisplatin and 609 (44%) received cetuximab; the median follow‐up was 3.5 years in the patients who remained alive. In the cetuximab cohort, CSM was significantly higher than in the cisplatin cohort (39% vs 25% at 3 years; P < .0001). In the matched cohorts (n = 414), the adjusted hazard ratio of CSM for cetuximab was 1.65 (95% confidence interval, 1.30‐2.09; P < .0001) relative to cisplatin, corresponding to an absolute difference of approximately 10% in both CSM and overall survival at 3 years. Cetuximab was associated with less dysphagia, more dermatitis, and a similar incidence of mucositis.

Conclusions

In this sizeable, national patient population, treatment with cetuximab was associated with significantly higher CSM than cisplatin. These results suggest that cisplatin may be the preferred chemotherapeutic agent in this setting.
The prognostic and predictive impact of inflammatory biomarkers in patients who have advanced‐stage cancer treated with immunotherapy
Authors: Bilen Mehmet A. , Martini Dylan J. , Liu Yuan , Lewis Colleen , Collins Hannah H. , Shabto Julie M. , Akce Mehmet , Kissick Haydn T. , Carthon Bradley C. , Shaib Walid L. , Alese Olatunji B. , Pillai Rathi N. , Steuer Conor E. , Wu Christina S. , Lawson David H. , Kudchadkar Ragini R. , El‐Rayes Bassel F. , Master Viraj A. , Ramalingam Suresh S. , Owonikoko Taofeek K. , Harvey R. Donald
Published: October 2018

Background

Optimal prognostic and predictive biomarkers for patients with advanced‐stage cancer patients who received immunotherapy (IO) are lacking. Inflammatory markers, such as the neutrophil‐to‐lymphocyte ratio (NLR), the monocyte‐to‐lymphocyte ratio (MLR), and the platelet‐to‐lymphocyte ratio (PLR), are readily available. The authors investigated the association between these markers and clinical outcomes of patients with advanced‐stage cancer who received IO.

Methods

A retrospective review was conducted of 90 patients with advanced cancer who received treatment on phase 1 clinical trials of IO‐based treatment regimens. NLR, MLR, and PLR values were log‐transformed and treated as continuous variables for each patient. Overall survival (OS), progression‐free survival (PFS), and clinical benefit were used to measure clinical outcomes. For univariate associations and multivariable analyses, Cox proportional‐hazards models or logistic regression models were used.

Results

The median patient age was 63 years, and most were men (59%). The most common histologies were melanoma (33%) and gastrointestinal cancers (22%). High baseline NLR, MLR, and PLR values were associated significantly with worse OS and PFS (P < .05) and a lower chance of benefit (NLR and PLR; P < .05). Increased NLR, MLR, and PLR values 6 weeks after baseline were associated with shorter OS and PFS (P ≤ .052).

Conclusions

Baseline and early changes in NLR, MLR, and PLR values were strongly associated with clinical outcomes in patients who received IO‐based treatment regimens on phase 1 trials. Confirmation in a homogenous patient population treated on late‐stage trials or outside of trial settings is warranted. These values may warrant consideration for inclusion when risk stratifying patients enrolled onto phase 1 clinical trials of IO agents.
A phase 1 study to assess the safety, tolerability, and pharmacokinetics of CXD101 in patients with advanced cancer
Authors: Eyre Toby A. , Collins Graham P. , Gupta Avinash , Coupe Nicholas , Sheikh Semira , Whittaker John , Wang Lai Mun , Campo Leticia , Soilleux Elizabeth , Tysoe Finn , Cousins Richard , La Thangue Nick , Folkes Lisa K. , Stratford Michael R. L. , Kerr David , Middleton Mark R.
Published: October 2018

Background

In the current study, the authors sought to determine the maximum tolerated dose (MTD) of the novel class 1 selective histone deacetylase inhibitor CXD101 in a dose escalation study in patients with advanced solid tumors or recurrent/refractory lymphoma.

Methods

The authors escalated the dose of CXD101 from 1 mg twice daily orally for 5 days in a 21‐day cycle (3+3 design).

Results

A total of 39 patients were enrolled, 36 of whom received CXD101. Of the 30 patients in the escalation cohort, 29 were evaluable for determination of the dose‐limiting toxicity (DLT). DLTs were noted at doses of 16 mg twice daily (1 of 6 patients), 20 mg twice daily (1 of 6 patients), and 24/25 mg twice daily (2 of 5 patients, both of whom developed neutropenic fever). The MTD was 20 mg twice daily, which achieved maximal plasma concentrations (±standard deviation) of 231±76 nM to 342±126 nM, which was within the biologically active range. Six patients received 20 mg twice daily in an expansion cohort. The most frequent adverse events were fatigue, nausea, and reversible cytopenia. Key grade 3 to 4 adverse events (according to Common Terminology Criteria for Adverse Events criteria [version 4.03]) included thrombocytopenia (11%), neutropenia (17%), and neutropenic fever (2%) across the 133 CXD101 cycles given. The toxicity profile was similar to that of licensing studies with other histone deacetylase inhibitors. In 22 evaluable patients receiving a dose of ≥16 mg twice daily (17 of whom had lymphoma and 5 of whom had solid tumors), 3 partial responses (2 in patients with classic Hodgkin lymphoma after allogenic stem cell transplantation and 1 in a patient with angioimmunoblastic T‐cell lymphoma) and 1 complete response (in a patient with follicular lymphoma) were noted (overall response rate of 18%) in addition to 9 patients who achieved durable stable disease. Responses were noted predominantly among patients with lymphoma (tumor reduction noted in 63% of patients on standard computed tomography).

Conclusions

The MTD in the current study was found to be 20 mg twice daily. Encouraging and durable activity was observed in patients with Hodgkin lymphoma, T‐cell lymphoma, and follicular lymphoma.
Whole mouse brain connectomics
Authors: Allan Johnson G. , Wang Nian , Anderson Robert J. , Chen Min , Cofer Gary P. , Gee James C. , Pratson Forrest , Tustison Nicholas , White Leonard E.
Published: October 2018

Methods have been developed to allow quantitative connectivity of the whole fixed mouse brain by means of magnetic resonance imaging (MRI). We have translated what we have learned in clinical imaging to the very special domain of the mouse brain. Diffusion tensor imaging (DTI) of perfusion fixed specimens can now be performed with spatial resolution of 45 μm3, that is, voxels that are 21,000 times smaller than the human connectome protocol. Specimen preparation has been optimized through an active staining protocol using a Gd chelate. Compressed sensing has been integrated into high performance reconstruction and post processing pipelines allowing acquisition of a whole mouse brain connectome in <12 hr. The methods have been validated against retroviral tracer studies. False positive tracts, which are especially problematic in clinical studies, have been reduced substantially to ~28%. The methods have been streamlined to provide high‐fidelity, whole mouse brain connectomes as a routine study. The data package provides holistic insight into the mouse brain with anatomic definition at the meso‐scale, quantitative volumes of subfields, scalar DTI metrics, and quantitative tractography.
Time‐Resolved Chemically Induced Dynamic Nuclear Polarization of Biologically Important Molecules
Authors: Morozova Olga B. , Ivanov Konstantin L.
Published: October 2018

In this work, we review the hyperpolarization technique named chemically induced dynamic nuclear polarization (CIDNP), focusing on the time‐resolved variant of this method and its biological applications. We introduce the main principles of polarization formation in liquids at high magnetic fields, provided by the so‐called spin sorting mechanism. Applications of CIDNP to studying fast reactions of short‐lived free radicals of biologically important molecules are discussed, as well as the potential of the method to probe the structure and magnetic parameters of such radicals. We also explain the principles of protein CIDNP and discuss applications of time‐resolved CIDNP to studies of protein structure and dynamics.
Experimental Evidence of the Mechanism of Selective Catalytic Reduction of NO with NH3 over Fe‐Containing BEA Zeolites
Authors: Boroń Paweł , Rutkowska Małgorzata , Gil Barbara , Marszałek Bartosz , Chmielarz Lucjan , Dzwigaj Stanislaw
Published: October 2018

Various temperature‐programmed techniques were used as tools in mechanistic studies of selective catalytic reduction (SCR) of NO with ammonia in the presence of Fe‐containing BEA zeolites. Moreover, FTIR studies of adsorbed NH3 and NO were conducted to determine the interactions of reactants with the catalyst surface. Iron was introduced into BEA zeolite by three different methods: i) two‐step post‐synthesis; ii) conventional wet impregnation; iii) ion exchange. The catalytic activity was dependent on the method used for iron introduction. The reactivities of NH3 and NO adsorbed on iron‐modified zeolites obtained by impregnation and ion‐exchange methods were higher than those measured for the catalyst obtained by a two‐step post‐synthesis method. The activity of Fe‐containing zeolites in SCR was related to the form of deposited iron species, as well as to the nature, strength, and concentration of acid sites. Possible reaction pathways of NO reduction over the FeBEA zeolite catalysts were presented and discussed.
In vivo metabolic and SHG imaging for monitoring of tumor response to chemotherapy
Authors: Lukina Maria M. , Dudenkova Varvara V. , Shimolina Lyubov’ E. , Snopova Ludmila B. , Zagaynova Elena V. , Shirmanova Marina V.
Published: October 2018

Although chemotherapy remains one of the main types of treatment for cancer, treatment failure is a frequent occurrence, emphasizing the need for new approaches to the early assessment of tumor response. The aim of this study was to search for indicators based on optical imaging of cellular metabolism and of collagen in tumors in vivo that enable evaluation of their response to chemotherapy. The study was performed on a mouse colorectal cancer model with the use of cisplatin, paclitaxel, and irinotecan. The metabolic activity of the tumor cells was assessed using fluorescence lifetime imaging of the metabolic cofactor reduced nicotinamide adenine dinucleotide (phosphate), NAD(P)H. Second harmonic generation (SHG) imaging was used to analyze the extent and properties of collagen within the tumors. We detected an early decrease in the free/bound NAD(P)H ratio in all treated tumors, indicating a shift toward a more oxidative metabolism. Monitoring of collagen showed an early increase in the amount of collagen followed by an increase in the extent of its orientation in tumors treated with cisplatin and paclitaxel, and decrease in collagen content in the case of irinotecan. Our study suggests that changes in cellular metabolism and fibrotic stroma organization precede morphological alterations and tumor size reduction, and that this indicates that NAD(P)H and collagen can be considered as intrinsic indicators of the response to treatment. This is the first time that these parameters have been investigated in tumors in vivo in the course of chemotherapy with drugs having different mechanisms of action. © 2018 International Society for Advancement of Cytometry
CD133 expression in circulating hematopoietic progenitor cells
Authors: Cimato Thomas R. , Conway Alexis , Nichols Julianne , Wallace Paul K.
Published: October 2018

Background

Circulating hematopoietic progenitors (HPCs) are involved in inflammatory diseases such as atherosclerosis, the immune response to cancer, and disorders of the hematopoietic system. HPC characterization by flow cytometry typically utilizes CD34 in combination with other cell surface markers to identify cell populations that give rise to specific hematopoietic lineages. CD133, also known as prominin‐1, is a cell surface protein found in HPCs that has a similar but not interchangeable expression pattern with CD34 for characterization of HPC populations. Our goal was to determine the distribution of CD133 expression within HPC sub‐types amongst circulating CD34+ cells.

Methods

The quantity of different HPC populations within the CD34+ CD133+ and CD34+ CD133− fractions of venous blood obtained from healthy human subjects was measured using multicolor flow cytometry.

Results

The majority of circulating CD34+ cells is CD133−. CD133+ CD34+ cells express low levels of CD38, contain cell populations bearing cell surface markers of hematopoietic stem cells, multipotent progenitors, and multilymphoid progenitors, and are largely devoid of CD38 expressing lineage specified progenitors. These findings clarify the composition of circulating CD133+ CD34+ cell types in adult human subjects. © 2018 International Clinical Cytometry Society
Distributed compressed sensing‐based multiuser channel estimation for frequency‐selective hybrid mmWave MIMO system
Authors: Zhang Ruoyu , Zhang Jiayan , Gao Yulong , Zhao Honglin
Published: October 2018

The multiuser millimeter wave (mmWave) MIMO system has been considered as a promising technology for future 5G cellular networks since high volume of data rates can be achieved by simultaneously supporting multiple users. However, the channel estimation is challenging due to the multiuser interference in frequency‐selective hybrid mmWave MIMO system. In this paper, we focus on the multiuser uplink wideband channel estimation with frequency selectivity. Specifically, a layer‐precoder reuse strategy is proposed, in which each transmission frame is divided into several subframes and the users share a common precoder at each subchannel of different subcarriers. Then, instead of only estimating channel of one user, multiuser frequency‐selective channel can be jointly estimated via a sparse recovery formulation. Furthermore, by exploiting the common sparsity among subchannels in frequency‐selective mmWave system, a distributed compressed sensing (DCS)–based channel estimation is proposed to jointly acquire the channel state information of all users via weighted least square to further reduce the pilot overhead. In addition, the Cramer‐Rao lower bound (CRLB) is derived for multiuser frequency‐selective channel estimation. Simulation results demonstrate that the proposed DCS‐based method can asymptotically approach the CRLB of channel estimation.
Sedimentology and the facies architecture of the Ghaggar‐Hakra Formation, Barmer Basin, India: Implications for early Cretaceous deposition on the north‐western Indian Plate margin
Authors: Beaumont Hazel , Clarke Stuart M. , Burley Stuart D. , Taylor Andrew M. , Mohapatra Pinakadhar
Published: October 2018

Fluvial strata of the Lower Cretaceous Ghaggar‐Hakra Formation are exposed in fault blocks on the central‐eastern margin of the Barmer Basin, Rajasthan. The sedimentology of these outcrops are described from 114 logs (thicknesses up to 100 m) and 53 two‐dimensional correlation panels. The formation comprises three distinct channel belt sandstone packages defined as the Darjaniyon‐ki Dhani, Sarnoo and Nosar sandstones separated by thick siltstone‐dominated floodplain successions. The sediments were deposited in a sub‐tropical, low sinuosity fluvial system that matures into a highly sinuous fluvial system. The Nosar Sandstone, the youngest of the three packages, exhibits a significant increase in energy and erosive power compared to those underlying it. This distinct change in fluvial style is interpreted as being rejuvenation due to an actively developing rift network forming accommodation space, rather than climatic controls acting on part of the depositional system. Consequently, the Ghaggar‐Hakra Formation at outcrop represents Lower Cretaceous syn‐rift deposition within the Barmer Basin with active localized fault movement from Nosar Sandstone times onward. These findings provide sedimentological evidence in support of pre‐Palaeogene northwest–southeast extension in the Barmer Basin. Moreover, they imply Cretaceous extension took place widely along the northern extremity of the West Indian Rift System consistent with plate tectonic models of the break‐up of Gondwana and evolution of the Indian Ocean. Outcrops of Lower Cretaceous strata are patchy across India and Pakistan. This study provides valuable material which, when combined with the available published data, facilitates a re‐evaluation of Lower Cretaceous palaeogeography for the north‐west Indian Plate. The reconstruction demonstrates a complex fluvial system, where the sediments are preserved sporadically as early syn‐rift strata. The findings imply a high preservation potential for early Cretaceous fluvial successions within rifted fault blocks near Saraswati and Aishwarya of the Barmer Basin beneath the Palaeogene fill that likely have significant potential for further hydrocarbon exploration.
A primer on investigating the role of the microbiome in brain and cognitive development
Authors: Kelsey Caroline , Dreisbach Caitlin , Alhusen Jeanne , Grossmann Tobias
Published: October 2018

Incorporating information regarding the gut microbiota into psychobiological research promises to shed new light on how individual differences in brain and cognitive development emerge. However, the investigation of the gut‐brain axis in development is still in its infancy and poses several challenges, including data analysis. Considering that the gut microbiome is an eco‐system containing millions of bacteria, one needs to utilize a breadth of methodologies and data analytic techniques. The present review serves two purposes. First, this review will inform developmental psychobiology researchers about the emerging study of the gut‐brain axis in development and second, this review will propose methodologies and data analytic strategies for integrating microbiome data in developmental research.
Metabolic and isotopic signature of short‐term DHEA administration in women: Comparison with findings in men
Authors: Buisson Corinne , Frelat Claire , Privat Kévin , Martinat Nicolas , Audran Michel , Collomp Katia
Published: October 2018

The impact of dehydroepiandrosterone (DHEA) administration has been widely studied for anti‐doping purposes in men, whereas only a few studies have been performed in women. In the present study, the impact of DHEA on the steroid profile parameters and their carbon isotopic ratios was explored. Eleven healthy young women and 10 healthy young men received two treatments: One with 100 mg/day of DHEA for 28 days and one with a placebo according to a double‐blind crossover protocol. Urine and saliva (only in females) samples were collected before and for 72 hours after each short‐term treatment. In all female subjects, concentrations of the urinary parameters of the steroid profile were highly impacted by short‐term DHEA administration including epitestosterone (E). Gas chromatography–combustion–isotope ratio mass spectrometry (GC–C–IRMS) analysis was performed and positive results were observed for E in the four female subjects where E concentration was adequate for such analysis, whereas men results remained negative for E. Last, the ability of the Anti‐Doping Administration and Management System (ADAMS) software used for the athlete biological passport to identify such doping was assessed. Of the 11 passports generated for female subjects, 10 were automatically classified as an atypical passport finding (ATPF). For the remaining passport with normal status in one woman, the variability of the concentrations prevented the ADAMS software from adjusting individual limits. The most impacted markers in women were T/E and 5αAdiol/E, with a detection window of 36 hours for 5αAdiol/E. In addition, good correlations were observed for DHEA and T concentrations in urine and saliva in females.
Development of a fluvoxamine detection system using a Quenchbody, a novel fluorescent biosensor
Authors: Sasao Ako , Takaki Michiyo , Jeong Hee‐Jin , Yonemitsu Kosei , Ohtsu Yuki , Tsutsumi Hiroshi , Furukawa Shota , Morioka Hiroshi , Ueda Hiroshi , Nishitani Yoko
Published: October 2018

The misuse of psychotropic drugs intended for medical treatment represents a recent worldwide public health concern. Quenchbody (Q‐body) is a novel fluoroimmunosensor that can detect an antigen immediately without additional reagents or washing steps. Here, we describe creating Q‐bodies for the detection of the antidepressant fluvoxamine (FLV) and determining optimal conditions to achieve the highest fluorescence intensity (FI). We prepared five Q‐bodies with the fluorophore labeled at either the N‐ or C‐ terminus and with different linker lengths. Fluorescence was measurable within minutes, indicating the interaction of Q‐bodies with FLV. The normalized FI (FI ratio) of the N‐terminus labeled Q‐body increased approximately 1.5‐fold upon FLV addition; Q‐bodies labeled at the C‐terminus did not significantly increase FI. Among the fluorescence dyes used in this study, Rhodamine 6G labeled Q‐body showed the best FI ratio. EC50 values of the N‐terminus labeled Q‐bodies were similar (23.2–224nM) regardless of linker length or labeling dye. We examined whether the Q‐body could be applicable to serum matrix instead of phosphate‐buffered saline. The intact serum interfered strongly with the Q‐body fluorescence. However, the FI ratios of the Q‐body for FLV‐spiked serum filtrate, for which proteins were removed by filtration, showed a dose‐dependency for detecting FLV levels. Deproteinization, which does not interfere with Q‐body fluorescence measurements, is likely necessary to detect serum FLV with high sensitivity. This study demonstrates the potential of Q‐body probes as a tool towards developing creative immunoassay applications.