bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune infiltration phenotypes of prostate adenocarcinoma and their clinical implications
Authors: Ma Zehua , Cheng Xiankui , Yue Ting , Shangguan Xun , Xin Zhixiang , Zhang Weiwei , Pan Jiahua , Wang Qi , Xue Wei 
Published: June 2021

AbstractBackgroundTumor‐infiltrating immune cells participate in the initiation and progression of prostate adenocarcinoma (PRAD). However, it is not fully known how immune infiltration affects the development of PRAD and its clinical presentation.MethodsHerein, we investigated the immune infiltration phenotypes in PRAD based on transcriptome profiles, methylation profiles, somatic mutation, and copy number variations. We also developed an immune prognostic model (IPM) to identify unfavorable prognosis. To verify this model, immunohistochemistry staining was performed on a cohort of PRAD samples. Moreover, we constructed a nomogram to assess the survival of PRAD incorporating immune infiltration and other clinical features.ResultsWe categorized PRAD patients into high and low‐level clusters based on immune infiltration phenotypes. The patients in the high‐level clusters had worse survival than their low‐level counterparts. Gene set enrichment analysis indicated that both anti‐ and pro‐tumor terms were enriched in high‐level cluster. Moreover, we identified a positive correlation between anti‐ and pro‐tumor immune cells in PRAD microenvironment. Notably, Somatic mutation analysis showed patients in high‐level cluster had a higher somatic mutation burden of KMT2D, HSPA8, CHD7, and MAP1A. In addition, we developed an IPM with robust predictive ability. The model can distinguish high‐risk PRAD patients with poor prognosis from low‐risk PRAD patients in both training and another three independent validation datasets. Besides, we constructed a nomogram incorporating Gleason score, pathological T stage, and IPM for the prognosis prediction of PRAD patients, which displayed robust predictive ability and might contribute to clinical practice.ConclusionOur work illustrated the immune infiltration phenotypes strongly related to the poor prognosis of PRAD patients, and highlighted the potential of the IPM to identify unfavorable tumor features.
Real time identification of anomalous events in coastal regions using deep learning techniques
Authors: Perumal Varalakshmi , Murugaiyan SureshKumar , Ravichandran Pavithran , Venkatesan R. , Sundar R. 
Published: June 2021

SummaryThe present existing weather prediction systems deployed by weather forecasting agencies predict the anomalous events using numerical simulation models developed based on geophysics and oceanographic theories. The major disadvantage with existing models is that are explicit simulation models. So, we try to build a real time prediction system that will automatically predict the intensity of any marine natural disaster events and alert the authorities to take necessary actions using a satellite and observational real time data set including moored met ocean data. We propose a novel hybrid model which is a combination of Convolutional Neural Network (CNN) and Long Short‐Term Memory (LSTM). The paper analyzes various other models such as Gated Recurrent Unit (GRU), Bidirectional LSTM (Bi‐LSTM) Recurrent Neural Network (RNN), and Extreme Learning Machine. In addition the other standard CNN architectures are also analyzed. Since the residual CNN network is the most effective architecture, the paper proposes a modification of the residual CNN network by combining the residual CNN network with LSTM/GRU RNN network along with a proposed new activation function which was experimentally proved to be more effective than the deep learning community standard activation function ReLU. The proposed new activation function overcomes the dead neuron propagation problem in ReLU activation function and hence the model's accuracy is increased by more than 1%. The proposed CNN + LSTM/GRU model is benchmarked with UCR time series benchmark dataset and it is experimentally seen that the model performs better than all existing algorithms.
Lightweight fog‐centric auditing scheme to verify integrity of IoT healthcare data in the cloud environment
Authors: Yoosuf Mohamed Sirajudeen , R Anitha 
Published: June 2021

SummaryIoT healthcare applications have become very popular among medical societies. At regular intervals, the healthcare IoT devices collect the patient's health information and transfer it to cloud storage. Storing the health records in the cloud environment increases the vulnerability. Integrity verification performed at regular intervals ensures the safety and security of the healthcare data stored in the cloud. Existing schemes use RSA and BLS signatures to verify the authenticity. However, the size of the signature is too large in RSA and BLS schemes. Using large signatures for proving the authenticity increases the computation overhead. IoT devices have minimal resource capacity, hence performing heavily weighted integrity schemes will create an unbearable workload. Likewise, private auditing increases the communication overhead between IoT devices and cloud storage. To overcome these issues, a fog‐centric auditing scheme is proposed based on the Cramer–Shoup cryptosystem. The proposed scheme allows the fog nodes to perform integrity verification without compromising security. It reduces the communication overhead by 55%–60%. The size of the CS signature used in the scheme is far lesser than the existing signatures. Moreover, performing the inline deduplication on the fog layer improves the efficiency of cloud storage by 30%.
Pharmacogenetics‐Guided Advances in Antipsychotic Treatment
Authors: Islam Farhana , Men Xiaoyu , Yoshida Kazunari , Zai Clement C. , Müller Daniel J. 
Published: June 2021

Pharmacogenetics (PGx) research over the past 2 decades has produced extensive evidence for the influence of genetic factors on the efficacy and tolerability of antipsychotic treatment. However, the application of these findings to optimize treatment outcomes for patients in clinical practice has been limited. This paper presents a meta‐review of key PGx findings related to antipsychotic response and common adverse effects, including antipsychotic‐induced weight gain, tardive dyskinesia (TD), and clozapine‐induced agranulocytosis (CIAG), and highlights advances and challenges in clinical implementation. Most robust findings from candidate gene and genomewide association studies were reported for associations between polymorphisms in CYP2D6 and exposure and response to specific antipsychotics. As a result, product labels and guidelines from various PGx expert groups have provided selection and dosing recommendations based on CYP2D6 metabolizer phenotypes for commonly prescribed antipsychotics. Other interesting genetic targets include DRD2 for antipsychotic response, SLC18A2 for TD, and the human leukocyte antigen (HLA) genes, HLA‐DQB1 and HLA‐B, for CIAG. Well‐designed studies using large, well‐characterized samples that leverages international collaborations are needed to validate previous findings, as well as discover new genetic variants involved in antipsychotic response and adverse effects.
Next‐generation Bruton's tyrosine kinase inhibitor BIIB091 selectively and potently inhibits B cell and Fc receptor signaling and downstream functions in B cells and myeloid cells
Authors: Bame Eris , Tang Hao , Burns Jeremy C , Arefayene Million , Michelsen Klaus , Ma Bin , Marx Isaac , Prince Robin , Roach Allie M , Poreci Urjana , Donaldson Douglas , Cullen Patrick , Casey Fergal , Zhu Jing , Carlile Thomas M , Sangurdekar Dipen , Zhang Baohong , Trapa Patrick , Santoro Joseph , Muragan Param , Pellerin Alex , Rubino Stephen , Gianni Davide , Bajrami Bekim , Peng Xiaomei , Coppell Alex , Riester Katherine , Belachew Shibeshih , Mehta Devangi , Palte Mike , Hopkins Brian T , Scaramozza Matthew , Franchimont Nathalie , Mingueneau Michael 
Published: June 2021

AbstractObjectivesBruton's tyrosine kinase (BTK) plays a non‐redundant signaling role downstream of the B‐cell receptor (BCR) in B cells and the receptors for the Fc region of immunoglobulins (FcR) in myeloid cells. Here, we characterise BIIB091, a novel, potent, selective and reversible small‐molecule inhibitor of BTK.MethodsBIIB091 was evaluated in vitro and in vivo in preclinical models and in phase 1 clinical trial.ResultsIn vitro, BIIB091 potently inhibited BTK‐dependent proximal signaling and distal functional responses in both B cells and myeloid cells with IC50s ranging from 3 to 106 nm, including antigen presentation to T cells, a key mechanism of action thought to be underlying the efficacy of B cell‐targeted therapeutics in multiple sclerosis. BIIB091 effectively sequestered tyrosine 551 in the kinase pocket by forming long‐lived complexes with BTK with t1/2 of more than 40 min, thereby preventing its phosphorylation by upstream kinases. As a key differentiating feature of BIIB091, this property explains the very potent whole blood IC50s of 87 and 106 nm observed with stimulated B cells and myeloid cells, respectively. In vivo, BIIB091 blocked B‐cell activation, antibody production and germinal center differentiation. In phase 1 healthy volunteer trial, BIIB091 inhibited naïve and unswitched memory B‐cell activation, with an in vivo IC50 of 55 nm and without significant impact on lymphoid or myeloid cell survival after 14 days of dosing.ConclusionPharmacodynamic results obtained in preclinical and early clinical settings support the advancement of BIIB091 in phase 2 clinical trials.
Spatial Gaussian processes improve multi‐species occupancy models when range boundaries are uncertain and nonoverlapping
Authors: Wright Wilson J. , Irvine Kathryn M. , Rodhouse Thomas J. , Litt Andrea R. 
Published: June 2021

Abstract

Species distribution models enable practitioners to analyze large datasets of encounter records and make predictions about species occurrence at unsurveyed locations. In omnibus surveys that record data on multiple species simultaneously, species ranges are often nonoverlapping and misaligned with the administrative unit defining the spatial domain of interest (e.g., a state or province). Consequently, some species display differentially restricted extents within a study area. Assuming hard boundaries based on expert opinion or published range maps to restrict species occurrence predictions implies a false sense of certainty in model‐based inferences.

We propose a multi‐species occupancy model with a spatial Gaussian process on site‐specific effects for each species as a model‐based solution. Specifying informative Bayesian hyperpriors on the spatial hyperparameters encapsulates broad‐scale correlation among site occupancy probabilities for each species. We fit this model to acoustic detection/nondetection data collected with autonomous recording units during summer of 2016–2019 throughout Oregon and Washington, USA, on 15 bat species.

We found vast improvements in spatial predictions of spotted bat (Euderma maculatum), canyon bat (Parastrellus hesperus), and Brazilian free‐tailed bat (Tadarida brasiliensis) when the available environmental predictors were insufficient for characterizing their restricted ranges within the region.

In contrast, widespread species (Lasionycteris noctivagans, Myotis californicus, Myotis evotis, Myotis volans) were appropriately modeled using only environmental predictors, such as percentage forest cover and cliff and canyon cover.

Utilizing spatial Gaussian processes within a community or multi‐species model incorporates uncertainty in range boundaries and allows for simultaneous predictions for the entire faunal assemblage even if species have nonoverlapping or restricted ranges within a spatial domain of interest. Such modeling improvements are essential if species distribution models are to accurately inform monitoring, species recovery plans, and other conservation efforts.
Exposure to a common antidepressant alters crayfish behavior and has potential subsequent ecosystem impacts
Authors: Reisinger Alexander J. , Reisinger Lindsey S. , Richmond Erinn K. , Rosi Emma J. 
Published: June 2021

AbstractPharmaceuticals are ubiquitous in aquatic environments, yet little is known regarding their impacts on ecological processes. Selective serotonin reuptake inhibitors (SSRIs) are frequently prescribed human antidepressants and have been shown to alter crayfish behavior. These behavioral alterations are particularly relevant as crayfish play a central role in freshwater ecosystems and often reach high biomass in anthropogenically influenced environments commonly exposed to pharmaceutical contamination. Using a 14‐d artificial stream experiment, we exposed spinycheek crayfish (Faxonius limosus) to citalopram, a common SSRI, at an environmentally realistic concentration (0.5 µg/L). We used a Y‐shaped flume to quantify the effects of SSRI exposure on crayfish behavior and food/conspecific preference. We also tested the interacting effects of citalopram and crayfish on habitat‐specific and whole‐stream ecosystem functions and biomass. Crayfish exposed to SSRIs exhibited increased boldness (time to emerge from shelters;P < 0.05) and spent more time orienting to food resources than nonexposed crayfish. Crayfish increased water column chlorophylla(P < 0.01) and benthic organic matter (P = 0.03). Furthermore, crayfish potentially increased water column respiration (P = 0.09) and potentially decreased nitrate uptake (P = 0.05). SSRI exposure exhibited a potential effect of decreasing benthic chlorophylla(P = 0.07), but there were no significant CRAY+SSRI interactions. Neither crayfish nor SSRI treatments affected whole‐stream metabolism. These results suggest that citalopram has the potential to affect algal biomass but did not affect ecosystem functioning. However, alterations to crayfish behavior driven by SSRI exposure could lead to subsequent ecosystem‐level effects as crayfish did affect various response metrics. We were unable to detect the effects of altered crayfish behavior at the ecosystem scale during our study, likely due to the short time frame (2 weeks) of our experiment. Further work is needed to quantify longer‐term ecosystem consequences of sublethal effects of pharmaceuticals, but these results show that ecological responses to pharmaceuticals should consider the entire ecosystem.
Low‐density aspen seedling establishment is widespread following recent wildfires in the western United States
Authors: Kreider Mark R. , Yocom Larissa L. 
Published: June 2021

AbstractSexual regeneration is increasingly recognized as an important regeneration pathway for aspen in the western United States, a region previously thought to be too dry for seedling establishment except for during unusually wet periods. Because of this historical assumption, information on aspen seedling establishment and factors influencing its occurrence is limited and frequently anecdotal. We conducted a systematic field survey of 15 recent fire footprints that burned in 2018 in the western United States to quantify how common aspen seedling establishment is following fire and to identify factors associated with establishment. We found aspen seedling establishment in 12 of 15 (80%) of fire footprints surveyed, although densities were mostly low. Establishment probability was positively associated with mean annual precipitation and negatively associated with seed‐source distance and the density of asexual aspen regeneration. Our results suggest that aspen seedling establishment may be a widespread, if often low‐density, feature in postdisturbance areas. Even in low numbers, aspen seedlings may play a disproportionately large role in aspen regeneration ecology, providing adaptive capacity and facilitating local range expansion.
Controlling the Activity of a Caged Cobalt‐Porphyrin‐Catalyst in Cyclopropanation Reactions with Peripheral Cage Substituents
Authors: Mouarrawis Valentinos , Bobylev Eduard O. , de Bruin Bas , Reek Joost N. H. 
Published: June 2021

AbstractIn this study, three novel cubic cages were synthesized and utilized to encapsulate a catalytically active cobalt(II) meso‐tetra(4‐pyridyl)porphyrin guest. The newly developed caged catalysts (Co‐G@Fe8(Zn‐L ⋅ 1)6, Co‐G@Fe8(Zn‐L ⋅ 2)6 and Co‐G@Fe8(Zn‐L ⋅ 3)6) can be easily synthesized and differ in exo‐functionalization, which are either none, polar or apolar groups. This leads to a different polarity of the peripheral environment surrounding the cage, which affects the (relative) local concentration of the substrates surrounding the cage and hence indirectly influences the substrate availability of the catalysis embedded in the active site of the caged catalyst systems. The resulting increased local substrate concentrations give rise to higher catalytic activities of the respective caged catalyst in metalloradical catalyzed cyclopropanation reactions. Interestingly, the catalytic activity is the highest when the apolar cage catalyst (Co‐G@Fe8(Zn‐L ⋅ 1)6) is used, and lowest with the polar analog (Co‐G@Fe8(Zn‐L ⋅ 3)6). In addition, the catalytic activity of the cage without exo‐functionalities (Co‐G@Fe8(Zn‐L ⋅ 2)6) is nearly two times lower than that of Co‐G@Fe8(Zn‐L ⋅ 1)6 and three times higher than that of Co‐G@Fe8(Zn‐L ⋅ 3)6, which further demonstrates the effect of the peripheral functionalities on the cyclopropanation reaction.
Hexadentate Poly‐Lewis Acids Based on 1,3,5‐Trisilacyclohexane
Authors: Schäfer Fabian , Neumann Beate , Stammler Hans‐Georg , Mitzel Norbert W. 
Published: June 2021

AbstractWe report the preparation of hexadentate poly‐Lewis acids (PLA) based on 1,3,5‐trisilacyclohexane backbones bearing two alkynyl groups attached to each of the silicon atoms. A rigid hexadentate PLA bearing six Lewis‐acidic catecholatoboryl‐substituents was prepared by a tin‐boron exchange reaction. Its structure, determined by X‐ray diffraction, is the first of a Lewis‐acid‐functionalised donor‐free trisilacyclohexane. Flexible hexadentate PLA were prepared by hydroboration or hydrosilylation of hexavinyltrisilacyclohexane, resulting in PLA with six 9‐BBN, SiCl3, SiCl2Me or SiClMe2 groups. The Lewis‐acidity of the last one was increased by conversion with silver triflate, resulting in a PLA with six highly acidic silyl triflate groups attached to the 1,3,5‐trisilacyclohexane unit as TfOSiMe2‐C2H4‐ groups. Host‐guest experiments of the above PLA demonstrated the suitability of the flexible representatives for complexation of neutral Lewis‐based guest molecules under formation of 1 : 6 adducts (host: guest).
Pd0‐Mediated Cross‐Coupling of [11C]Methyl Iodide with Carboxysilane for Synthesis of [11C]Acetic Acid and its Active Esters: 11C‐Acetylation of Small, Medium, and Large Molecules
Authors: Doi Hisashi , Goto Miki , Sato Yuzuru 
Published: June 2021

AbstractA rapid Pd0‐mediated cross‐coupling of [11C]CH3I with carboxytriphenylsilane (1) to synthesize [2‐11C]acetic acid ([11C]2) and its corresponding imidyl esters as radiolabeling reagents for 11C‐acetylation is reported. The reaction of [11C]CH3I with 1 using a Pd2(dibenzylideneacetone)3/P(o‐tolyl)3 (1 : 4) catalyst in tetrahydrofuran/H2O (9 : 1) at 90 °C for 4 min afforded [11C]2 having satisfactory radioactivity and a good yield. The coupling of the cationic carbon atom of methyl iodide and the carboxyl group in 1 is an ionicity‐driven reversed‐polarity reaction. An injectable radiopharmaceutical formulation of [11C]2 prepared using 33 GBq of [11C]CH3I had a radioactivity of 7.4–7.8 GBq, and the decay‐corrected radiochemical yield of [11C]CH3I into [11C]2 was 63–73 %. [11C]2 was converted to [2‐11C]acetic acid phthalimidyl ester ([11C]3) or its succinimidyl ester ([11C]10), which were used for the 11C‐acetylation of 4‐aminophenol, oxytocin, and albumin. Injectable solutions of these products (0.25–2.0 GBq) are suitable for in vivo positron emission tomography studies.
The genomic origin of Zana of Abkhazia
Authors: Margaryan Ashot , Sinding Mikkel‐Holger S. , Carøe Christian , Yamshchikov Vladimir , Burtsev Igor , Gilbert M. Thomas P. 
Published: June 2021

AbstractEnigmatic phenomena have sparked the imagination of people around the globe into creating folkloric creatures. One prime example is Zana of Abkhazia (South Caucasus), a well‐documented 19th century female who was captured living wild in the forest. Zana's appearance was sufficiently unusual, that she was referred to by locals as an Almasty—the analog of Bigfoot in the Caucasus. Although the exact location of Zana's burial site was unknown, the grave of her son, Khwit, was identified in 1971. The genomes of Khwit and the alleged Zana skeleton were sequenced to an average depth of ca. 3× using ancient DNA techniques. The identical mtDNA and parent‐offspring relationship between the two indicated that the unknown woman was indeed Zana. Population genomic analyses demonstrated that Zana's immediate genetic ancestry can likely be traced to present‐day East‐African populations. We speculate that Zana might have had a genetic disorder such as congenital generalized hypertrichosis which could partially explain her strange behavior, lack of speech, and long body hair. Our findings elucidate Zana's unfortunate story and provide a clear example of how prejudices of the time led to notions of cryptic hominids that are still held and transmitted by some today.
Enrichment of polychlorinated biphenyls in river water by using magnetic adsorbents with high selectivity to nonplanar aromatic compounds and their analysis with gas chromatography–mass spectrometry
Authors: Wang Xuesong , Li Chunyan , Wu Dan , Shen Jiwei , Wei Yinmao , Wang Chaozhan 
Published: June 2021

AbstractPreviously our group reported a magnetic adsorbent, magGO@bottlebrush, which has high selectivity to nonplanar aromatic compounds with two or more phenyl rings. In this work, the magGO@bottlebrush was used for pre‐concentration of seven frequently concerned polychlorinated biphenyls (PCB28, PCB52, PCB101, PCB118, PCB138, PCB153, and PCB180) from river water samples, considering PCBs are hydrophobic compounds with two substituted benzene rings and have nonplanar structure, and gas chromatography–mass spectrometry (GC–MS) was used for the quantification. Several parameters affecting the extraction efficiency of the seven PCBs were investigated, under the best concerned extraction conditions, the developed method had excellent linearity (R2 > 0.9951) within the range of 1–100 pg/ml, it also possessed low limits of detection (0.33–0.90 pg/ml, S/N = 3) for the PCBs. Then, the enrichment and detection methods were applied to determine PCBs in two local rivers. PCB101, PCB118, and PCB138 were detected in one river, and their concentrations were 1.31, 0.69, and 10.01 pg/ml, respectively. The spiked recoveries of the river water samples were 63.33–119.29%, and the relative SD values were less than 17.33%. These results show that the proposed method has great potential application for the analysis of PCBs in river water samples.