bluuebunny/crossref_metadata_2025 huggingface dataset:
Self‐reported olfactory and gustatory dysfunction and psychophysical testing in screening for COVID‐19: A systematic review and meta‐analysis
Authors: Hoang Minh P. , Staibano Phillip , McHugh Tobial , Sommer Doron D. , Snidvongs Kornkiat
Published: November 2021

Background

A substantial proportion of coronavirus disease‐2019 (COVID‐19) patients demonstrate olfactory and gustatory dysfunction (OGD). Self‐reporting for OGD is widely used as a predictor of COVID‐19. Although psychophysical assessment is currently under investigation in this role, the sensitivity of these screening tests for COVID‐19 remains unclear. In this systematic review we assess the sensitivity of self‐reporting and psychophysical tests for OGD.

Methods

A systematic search was performed on PubMed, EMBASE, and ClinicalTrials.gov from inception until February 16, 2021. Studies of suspected COVID‐19 patients with reported smell or taste alterations were included. Data were pooled for meta‐analysis. Sensitivity, specificity, and diagnostic odds ratio (DOR) were reported in the outcomes.

Results

In the 50 included studies (42,902 patients), self‐reported olfactory dysfunction showed a sensitivity of 43.9% (95% confidence interval [CI], 37.8%‐50.2%), a specificity of 91.8% (95% CI, 89.0%‐93.9%), and a DOR of 8.74 (95% CI, 6.67‐11.46) for predicting COVID‐19 infection. Self‐reported gustatory dysfunction yielded a sensitivity of 44.9% (95% CI, 36.4%‐53.8%), a specificity of 91.5% (95% CI, 87.7%‐94.3%), and a DOR of 8.83 (95% CI, 6.48‐12.01). Olfactory psychophysical tests analysis revealed a sensitivity of 52.8% (95% CI, 25.5%‐78.6%), a specificity of 88.0% (95% CI, 53.7%‐97.9%), and a DOR of 8.18 (95% CI, 3.65‐18.36). One study used an identification test for gustatory sensations assessment.

Conclusion

Although demonstrating high specificity and DOR values, neither self‐reported OGD nor unvalidated and limited psychophysical tests were sufficiently sensitive in screening for COVID‐19. They were not suitable adjuncts in ruling out the disease.
The epidemiology is promising, but the trial evidence is weak. Why pharmacological dementia risk reduction trials haven't lived up to expectations, and where do we go from here?
Authors: Peters Ruth , Dodge Hiroko H. , James Sarah , Jicha Gregory A. , Meyer Pierre‐Francois , Richards Marcus , Smith A. David , Yassine Hussein N. , Abner Erin , Hainsworth Atticus H. , Kehoe Patrick G. , Beckett Nigel , Anderson Craig S. , Anstey Kaarin J.
Published: November 2021

There is an urgent need for interventions that can prevent or delay cognitive decline and dementia. Decades of epidemiological research have identified potential pharmacological strategies for risk factor modification to prevent these serious conditions, but clinical trials have failed to confirm the potential efficacy for such interventions. Our multidisciplinary international group reviewed seven high‐potential intervention strategies in an attempt to identify potential reasons for the mismatch between the observational and trial results. In considering our findings, we offer constructive recommendations for the next steps. Overall, we observed some differences in the observational evidence base for the seven strategies, but several common methodological themes that emerged. These themes included the appropriateness of trial populations and intervention strategies, including the timing of interventions and other aspects of trials methodology. To inform the design of future clinical trials, we provide recommendations for the next steps in finding strategies for effective dementia risk reduction.
Neuropsychological, neuropsychiatric, and quality‐of‐life assessments in Alzheimer's disease patients treated with plasma exchange with albumin replacement from the randomized AMBAR study
Authors: Boada Mercè , López Oscar L. , Olazarán Javier , Núñez Laura , Pfeffer Michael , Puente Orlando , Piñol‐Ripoll Gerard , Gámez José E. , Anaya Fernando , Kiprov Dobri , Alegret Montserrat , Grifols Carlota , Barceló Miquel , Bozzo Jordi , Szczepiorkowski Zbigniew M. , Páez Antonio ,   the AMBAR Trial Group
Published: November 2021

Introduction

We report the effects of plasma exchange (PE) with albumin replacement on neuropsychological, neuropsychiatric, and quality‐of‐life (QoL) outcomes in mild‐to‐moderate Alzheimer's disease (AD) patients in a phase 2b/3 trial (Alzheimer's Management by Albumin Replacement [AMBAR] study).

Methods

Three hundred forty‐seven patients were randomized into placebo (sham‐PE) and three PE‐treatment arms with low/high doses of albumin, with/without intravenous immunoglobulin (IVIG). Specific test measurements were performed at baseline; month 2 (weekly conventional PE); months 6, 9, and 12 (monthly low‐volume PE [LVPE]); and month 14.

Results

The PE‐treated mild‐AD cohort improved their language fluency and processing speed versus placebo at month 14 (effect sizes: >100%; P‐values: .03 to .001). The moderate‐AD cohort significantly improved short‐term verbal memory (effect sizes: 94% to >100%; P‐values: .02 to .003). The progression of the neuropsychiatric symptoms of PE‐treated was similar to placebo. Mild‐AD patients showed improved QoL (P‐values: .04 to .008).

Discussion

PE‐treated AD patients showed improvement in memory, language abilities, processing speed, and QoL‐AD. No worsening of their psychoaffective status was observed.
Tumorzellspezifisches Targeting von Ibrutinib: Einführung von elektrostatischen Antikörper‐Inhibitor‐Konjugaten (AiCs)
Authors: Faust Andreas , Bäumer Nicole , Schlütermann Alina , Becht Manuel , Greune Lilo , Geyer Christiane , Rüter Christian , Margeta Renato , Wittmann Lisa , Dersch Petra , Lenz Georg , Berdel Wolfgang E. , Bäumer Sebastian
Published: November 2021

Ibrutinib ist ein Inhibitor der Bruton‐Tyrosinkinase, der für die Behandlung von Patienten mit chronischer lymphatischer Leukämie, Mantelzell‐Lymphom und Waldenström‐Makroglobulinämie zugelassen und mit Nebenwirkungen verbunden ist. Um seine Toxizität zu minimieren, haben wir Ibrutinib mit einem zellgerichteten, internalisierenden Antikörper verbunden. Dazu synthetisierten wir ein polyanionisches Derivat, Ibrutinib‐Cy3.5, das seine volle Funktionalität beibehält. Dieser anionische Inhibitor wird durch unser Anti‐CD20‐Protamin‐Targeting‐Konjugat und freies Protamin komplexiert und assembliert dadurch spontan zu einem elektrostatisch stabilisierten vesikulären Nanoträger. Die Komplexierung führte zu einer Akkumulation des Wirkstoffs, der durch die CD20‐Antigen‐Internalisierung in die Zellen aufgenommen und in seiner Wirksamkeit verstärkt wurde. In vivo beobachteten wir eine signifikante Anreicherung des Wirkstoffs in Xenotransplantat‐Lymphom‐Tumoren bei Mäusen mit defizientem Immunsystem und eine signifikant verbesserte Reaktion auf niedrigere Dosen im Vergleich zum ursprünglichen Wirkstoff.
Substitution of diarylphosphoryl azides with aliphatic amines catalyzed by simple rare‐earth metal salts: Efficient and novel preparation of phosphoryl amides
Authors: Peng Xin‐Hua , Bai Rui , Liu Shanshan , Li Zhuo , Jiao Lin‐Yu
Published: November 2021

A novel and high efficient protocol was disclosed herein for the rare‐earth metal salt‐catalyzed substitution of phosphoryl azides with amines. In this homogeneous catalysis system, different diarylphosphoryl azides and aliphatic and aromatic amines were evaluated under the optimized reaction conditions, and a series of phosphoryl amides were generated through LaCl3 catalysis for the first time in moderate to excellent isolated yields. Different from well‐tolerated phosphoryl azide substrates, the amino nucleophiles, however, were mainly limited to primary amines; their secondary analogues or anilines were reluctant to experience desired transformations. Nevertheless, this methodology has proven to be a simple, practical, and scalable application of the promising lanthanide catalyst toward the exiting methodology library to prepare phosphoryl amides.
Separation of squalene from olive oil deodorizer distillate using short‐path molecular distillation
Authors: Cetinbas Sena , Gumus‐Bonacina Cansu Ekin , Tekin Aziz
Published: November 2021

Squalene was recovered from an olive oil deodorizer distillate (OODD) containing 40% of squalene by a two‐step process. The first step was to esterify the free fatty acids (FFAs) to make them less volatile. The second step was to separate the squalene by molecular distillation. The best esterification conditions were found to be 190°C and 360 min, where FFA content of the reaction mixture was reduced from 49.3% to 7.9%, however, an inevitable squalene loss (30%) was also observed due to a discontinuous operation. The remaining squalene (28%) in the esterified mixture was then distilled using a molecular distillation unit at elevated temperatures (190–230°C) and pressures (0.05–5 mmHg). When the temperature and vacuum during distillation increased, FFA content in the distillate reduced while distillate yield and squalene purity increased. The highest distillate yield (27.7%) and squalene purity (98.1%) were obtained at the highest applied temperature (230°C) under the lowest absolute pressure (0.05 mmHg), where FFA content of distillate was measured as 1.8%. High percentage of squalene (95%–98%) could be distilled at 230°C between 0.05 and 0.5 mmHg absolute pressures. The overall squalene recovery after all treatments was calculated as 68%.
Association Between Gut Microbiota and Elevated Serum Urate in Two Independent Cohorts
Authors: Wei Jie , Zhang Yuqing , Dalbeth Nicola , Terkeltaub Robert , Yang Tuo , Wang Yilun , Yang Zidan , Li Jiatian , Wu Ziying , Zeng Chao , Lei Guanghua
Published: November 2021

Objective

Hyperuricemia is a precursor to gout and is often present in other metabolic diseases that are promoted by microbiome dysbiosis. We undertook this study to examine the association of gut microbiota with hyperuricemia and serum urate levels in humans.

Methods

Study participants were derived from a community‐based observational study, the Xiangya Osteoarthritis Study (discovery cohort). Hyperuricemia was defined as the presence of a serum urate level >357 μmoles/liter in women and >416 μmoles/liter in men. Gut microbiota were analyzed using 16S ribosomal RNA sequencing of stool samples. We examined the relationship of microbiota dysbiosis (i.e., richness, diversity, composition, and relative abundance of microbiota taxa) and predicted functional pathways to prevalent hyperuricemia and serum urate levels. We verified the associations in an independent observational study, the Step Study (validation cohort).

Results

The discovery cohort consisted of 1,392 subjects from rural areas (mean age 61.3 years, 57.4% women, 17.2% with hyperuricemia). Participants with hyperuricemia had decreased richness and diversity, altered composition of microbiota, and lower relative abundances of genus Coprococcus compared to those with normouricemia. Predicted KEGG metabolism pathways including amino acid and nucleotide metabolisms were significantly altered in subjects with hyperuricemia compared to those with normouricemia. Gut microbiota richness, diversity, and low relative abundances of genus Coprococcus were also associated with high levels of serum urate. These findings were replicated in the validation cohort with 480 participants.

Conclusion

Gut microbiota dysbiosis is associated with elevated serum urate levels. Our study examines the possibility that microbiota dysbiosis may modulate these levels.
Gene–environment interaction identification via penalized robust divergence
Authors: Ren Mingyang , Zhang Sanguo , Ma Shuangge , Zhang Qingzhao
Published: November 2021

In high‐throughput cancer studies, gene–environment interactions associated with outcomes have important implications. Some commonly adopted identification methods do not respect the “main effect, interaction” hierarchical structure. In addition, they can be challenged by data contamination and/or long‐tailed distributions, which are not uncommon. In this article, robust methods based on ‐divergence and density power divergence are proposed to accommodate contaminated data/long‐tailed distributions. A hierarchical sparse group penalty is adopted for regularized estimation and selection and can identify important gene–environment interactions and respect the “main effect, interaction” hierarchical structure. The proposed methods are implemented using an effective group coordinate descent algorithm. Simulation shows that when contamination occurs, the proposed methods can significantly outperform the existing alternatives with more accurate identification. The proposed approach is applied to the analysis of The Cancer Genome Atlas (TCGA) triple‐negative breast cancer data and Gene Environment Association Studies (GENEVA) Type 2 Diabetes data.
Stakeholder engagement in business models for sustainability: The stakeholder value flow model for sustainable development
Authors: Attanasio Giovanna , Preghenella Nadia , De Toni Alberto Felice , Battistella Cinzia
Published: November 2021

This paper aims to investigate how stakeholder groups engaged by the company contribute to the value flow of business models for sustainability. The research aims to expand the knowledge on business models for sustainability by highlighting the most important contributions of stakeholders that are relevant from a value flow and sustainable development perspective. The research methodology is a multiple case study in five Italian B corporations. The paper contribution is a stakeholder value flow model of business models for sustainability that categorizes the stakeholders engaged in the specific value flow dimension, namely, value intention, value proposition, value creation, value delivery and value capture. The stakeholder value flow model can facilitate a systematic and deeper analysis of stakeholder contributions to the company business model. Moreover, the stakeholder value flow model can be used to map from the company perspective the most significant relationships and to facilitate the stakeholder engagement towards sustainable development.
Low carbon transition risk in mutual fund portfolios: Managerial involvement and performance effects
Authors: Reboredo Juan C. , Otero González Luis A.
Published: November 2021

Transitioning to a low‐carbon economy to mitigate the effects of climate change involves risks. We investigate the effects of managerial ownership and management on the low carbon transition risk of mutual fund portfolios and the effects of low carbon transition risk on mutual fund performance and flows. Using low carbon transition risk ratings based on the unmanaged carbon risk of the companies included in fund portfolios, we find that managerial ownership and the socially responsible focus of the fund reduce fund portfolio exposure to carbon risk, whereas active management has the opposite effect. Furthermore, we find that funds with low carbon transition risk produce a better risk‐adjusted performance are more sensitive to tail risks and exhibit a better fund flow performance.
Characteristics of contrast‐enhanced ultrasound for diagnosis of solid clear cell renal cell carcinomas ≤4 cm: A meta‐analysis
Authors: Liu Yang , Kan Yanmin , Zhang Jincun , Li Ning , Wang Yihua
Published: November 2021

Now solid renal tumors ≤4 cm is the most common, especially the subtype of clear cell renal cell carcinoma (ccRCC) of malignant kidney tumors in clinical. However, there is not specific characteristics of contrast‐enhanced ultrasound (CEUS) be recommended by the EFSUMB Guidelines in distinguish the essence of the kidney tumor with different sizes. Therefore, this meta‐analysis aimed to assess the ability of CEUS to diagnose solid ccRCC (sccRCC) ≤4 cm. We comprehensively searched the Cochrane Library, Embase, PubMed, and Web of Science databases from their inception to 28 July 2020, for studies reporting the CEUS features of sccRCC lesions ≤4 cm. Additional articles were identified through the Chinese National Knowledge Infrastructure database. Studies were selected independently by two investigators and the relevant data were extracted. Discrepancies were resolved via discussion with the senior author. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies‐2 tool, and the sensitivity and specificity of each study were determined and plotted as a receiver operating characteristic curve. Ten studies were included in this meta‐analysis. Hyperenhancement showed medium sensitivity (67%–89%) and specificity (42%–75%) for diagnosing sccRCC ≤4 cm, fast‐in contrast agent and heterogeneous enhancement showed high diagnostic abilities (area under curve (AUC) 0.74–0.84), but the presence of a pseudocapsule and fast‐out contrast agent had poor diagnostic ability (AUC <0.70). The combination of hyperenhancement and iso‐enhancement showed high sensitivity (98%) for diagnosing sccRCC ≤4 cm. Hyperenhancement, fast‐in contrast agent, and heterogeneous enhancement may be specific features that could help to identify sccRCC ≤4 cm, while the presence of a pseudocapsule and fast‐out of contrast agent may have low diagnostic values. The combination of multiple indexes may improve the diagnostic value of CEUS for sccRCC ≤4 cm.
Treatment patterns and survival in metastatic castration‐sensitive prostate cancer in the US Veterans Health Administration
Authors: Freedland Stephen J. , Sandin Rickard , Sah Janvi , Emir Birol , Mu Qiao , Ratiu Anna , Hong Agnes , Serfass Lucile , Tagawa Scott T.
Published: November 2021

Background

Limited real‐world data exist on treatment patterns and outcomes in patients with metastatic castration‐sensitive prostate cancer (mCSPC).

Methods

A retrospective cohort study was conducted, using the Veterans Health Administration claims database (April 2013–March 2018). Among 369,734 prostate cancer patients, we selected all men who developed metastases within 90 days before or after medical/surgical castration and who received androgen deprivation therapy (ADT). Patients were categorized into four cohorts: ADT‐only (± <90‐day nonsteroidal anti‐androgen [NSAA] use), ADT + NSAA, ADT + docetaxel, and ADT + abiraterone. Main outcomes were treatment patterns, time‐to‐progression to metastatic castration‐resistant disease, and overall survival. Multivariable analysis and sensitivity analysis were conducted.

Results

Of 1395 patients, 874 (63%) received ADT‐only, 338 (24%) received ADT + NSAA, 108 (8%) received ADT + docetaxel, and 75 (5%) received ADT + abiraterone. Proportions on ADT‐only and ADT + NSAA declined (from 66% to 60% and from 31% to 17%, respectively) over the study period, while proportions prescribed ADT + docetaxel or abiraterone increased from 3% to 9% and from 1% to 15%, respectively. Patients treated with ADT + NSAA had similar risks of castration‐resistant disease (hazard ratio [HR] 1.05; 95% confidence interval [CI]: 0.87, 1.26) and overall mortality (HR 1.22; 95% CI: 0.97, 1.54) as ADT‐only.

Conclusions

Most patients with mCSPC initiating ADT received ADT‐only or ADT + NSAA, despite the emergence of docetaxel and novel hormonal therapies. Even in the most recent period (2017 to early 2018), only 24% of men received intensified therapy with agents known to prolong survival versus ADT‐only. These data in real‐world clinical practice suggest substantial room for improved outcomes in patients with mCSPC.
Global students' counselling self‐efficacy and experiences of a United States‐based counselling training programme
Authors: Basma Dareen , Chen Szu‐Yu
Published: November 2021

Distance counsellor education programmes in the United States have expanded educational opportunities for global students to pursue counselling training while remaining in their home countries. The purpose of this mixed‐methods study was to explore global counselling students' and recent counselling graduates' perceived applicability and practicality of the learned counselling knowledge, skills and interventions within their own global and cultural communities. A total of 12 individuals participated in the study; results showed that participants believed that they were capable of demonstrating helping skills and effectively working with clients. Qualitative findings identified participants' need for additional programmatic and institutional support and globally inclusive curriculum. The authors discuss implications for counsellor educators who provide distance counselling training for global students. Finally, the authors provide recommendations for future research to enhance the quality of distance counselling training in counsellor education programmes.
Laminar Fluid Mixing in Micromixers: Description of Pull‐Push Effects
Authors: Haghighinia Arash , Movahedirad Salman , Azad Babak Kamali Doust
Published: November 2021

A numerical study was performed on laminar mixing of fluids by means of embedded microbarriers against the flow direction in two three‐dimensional T‐micromixers. Two microchannels with different obstacle arrangements were considered, and the effect of volumetric flow rate Q on two‐stream pull‐push motion was investigated. With increasing Q and distance of the barriers to the sidewalls K, different vortices and fluid movement patterns develop in the two micromixers. Maximum mass transfer is obtained for the micromixer with smaller K value. With decreasing K, pull‐push movement strongly affects fluid merging, and the quality of mixing increases. Moreover, the effect of fluid tortuosity was studied, and a direct relationship between hydrodynamic fluid tortuosity and mass transfer was found.
Metal‐Free Synthesis of Benzo[a]phenanthridines from Aromatic Aldehydes, Cyclohexanones, and Aromatic Amines
Authors: Jiang Pingyu , Shan Zhifei , Chen Shanping , Wang Quanyuan , Jiang Shuxin , Zheng Haolin , Deng Guo‐Jun
Published: November 2021

Comprehensive Summary

A three‐component synthesis of benzo[α]phenanthridines from aromatic aldehydes, cyclohexanones, and aromatic amines has been developed, which is mediated by KI/DMSO/camphorsulfonic acid to afford a variety of functionalized benzo[α]phenanthridines in satisfactory yields. The present strategy provides a biaryl motif ortho to the nitrogen atom which has the potential to be used as ligand by further modification. With the advantages of readily available starting materials, transition‐metal‐free conditions, gram‐scale synthesis, and broad substrate scope, this three‐component protocol provides an efficient approach for the preparation of diverse benzo[α]phenanthridines.
Cyclic (Amino)(Aryl)Nitrenium Cations with Lewis Acidity Controlled by Remote Substituents
Authors: Wang Wenqing , Zheng Xin , Zhang Leran , Li Shunjie , Zhao Yue , Wang Xinping
Published: November 2021

Comprehensive Summary

N‐Heterocyclic nitrogen Lewis acids are important in synthetic chemistry. Stable cyclic (amino)(aryl)nitrenium cations, cyc‐1+—cyc‐3+, were synthesized by chemical oxidation of aryl azo compounds with different substituents, iPr, H and I, at the para positions of the phenyl group. The excited triplet states of cyc‐1+—cyc‐3+ abstract H‐atoms step by step to generate radical intermediates cyc‐1H•+—cyc‐3H•+ traced by EPR spectroscopy and products cyc‐1H2+—cyc‐3H2+ characterized by single crystal X‐ray diffraction. The Lewis acidity of species cyc‐1+—cyc‐3+ are remote substituent‐dependent. Cyc‐2+—cyc‐3+ have much higher acidity than those previously reported congeners based on energies of LUMOs. The electrophilicity enables them to form Lewis adducts with neutral Lewis base Me3P, and to gain one‐electron to produce neutral radicals cyc‐1•—cyc‐3•.
Factors Affecting the Catalytic Performance of Nano‐catalysts
Authors: Yang Hongling , Wu Yue , Zhuang Zewen , Li Yang , Chen Chen
Published: November 2021

Comprehensive Summary

Nano‐catalysis plays a vital role in the industrially chemical transformations. The increasingly severe energy crisis and environmental issues spur scientists to exploit novel nano‐catalysts in diverse fields. It is essential to understand the fundamental physicochemical properties of nano‐catalysts to develop efficient systems, whose design can be subsequently precisely tuned at the atomic level. In this review, we summarize several key factors affecting the catalytic activity of nano‐catalysts, including structure, composition, size, and interface, providing guidance for the atomic level control of high‐efficient nano‐catalysts. Finally, we present a brief conclusion and some thoughts on nano‐catalysis.

What is the most favorite and original chemistry developed in your research group?

Nanomaterials for catalysis and renewable energy.

How do you supervise your students?

I always encourage my students to innovate, persist and enjoy their researches.

What is the most important personality for scientific research?

Strong interest.

What are your hobbies? What's your favorite book(s)?

Reading, travelling and gaming. My favorite books are novels that give me a variety of different experiences.

How do you keep balance between research and family?

I always try to make time to be with my family, however busy I am.
Clofarabine monotherapy in two patients with refractory Langerhans cell histiocytosis
Authors: Irie Masahiro , Nakano Tomohiro , Katayama Saori , Suzuki Tasuku , Moriya Kunihiko , Watanabe Yuko , Suzuki Nobu , Saitoh‐Nanjyo Yuka , Onuma Masaei , Rikiishi Takeshi , Niizuma Hidetaka , Sasahara Yoji , Kure Shigeo
Published: November 2021

Background

Better therapeutic options other than conventional chemotherapy for pediatric patients with refractory Langerhans cell histiocytosis (LCH) remain undetermined.

Case

We successfully treated two patients with refractory and risk organ negative LCH with clofarabine (CLO) monotherapy after recurrence. We administered total 23 courses of CLO monotherapy in patient 1 and 4 courses in patient 2. Both patients had distinct clinical manifestations but achieved a durable complete response with acceptable adverse effects of transient myelosuppression. CLO monotherapy was still effective when he had the second recurrent lesion after first completion of CLO in patient 1. We could discontinue prednisolone to control his refractory inflammation of LCH after completing CLO chemotherapy in patient 2.

Conclusion

Although large‐scale studies are warranted, CLO monotherapy could be a therapeutic option for high efficacy and feasibility besides other intensive combination chemotherapies or allogeneic hematopoietic stem cell transplantation for refractory LCH without risk organ involvement in children.
Data dissemination approach using machine learning techniques for WBANs
Authors: Punj Roopali , Kumar Rakesh
Published: November 2021

Nowadays, the technological advancements of low power electronic and sensing devices, wearable systems, communication technologies, and cloud computing have encouraged the provision of ubiquitous health monitoring, medical diagnosis, and treatment consultations. The data collected from the patients are transmitted to mHealth server for real‐time and self‐reliant activity detection, behavior analysis, ambient assisted living, elderly care, activity of daily living, rehabilitations, entertainments, and surveillance in smart home environments. This helps in building sensor analyst systems that analyze the data on mHealth server for disseminating it to the respective end users. This is of utmost importance as it can provide real time feedback to patients, family members, caregivers, and so forth about the behavioral changes of elderly people and people with special needs. In this article, we have proposed knowledge based data dissemination system using machine learning techniques that analyses the data collected on mHealth server in three steps. First, the data are analyzed using support vector machine, k‐nearest neighbor, neural network, and logistic regression. Second, it finds hidden patterns from the data using hidden Markov model (HMM). Third, it defines fuzzy rules to disseminate the data to the end users. The system has been compared against conventional approaches. The uniqueness of the system lies in the fact that it uses temporal nature of data and provides with real‐time feedback as well as predicts outcomes and detects hidden patterns. The results have shown that the techniques NN, HMM, and fuzzy logic when used in conjunction with each other for disease prediction, hidden pattern detection, and data dissemination gives an accuracy of 98%. Thus, increasing effectiveness of sensor analyst system.
Sustainable Flow‐Synthesis of (Bulky) Nucleoside Drugs by a Novel and Highly Stable Nucleoside Phosphorylase Immobilized on Reusable Supports
Authors: Benítez‐Mateos Ana I. , Paradisi Francesca
Published: November 2021

The continuous synthesis of valuable nucleoside drugs was achieved in up to 99 % conversion by using a novel halotolerant purine nucleoside phosphorylase from Halomonas elongata (HePNP). HePNP showed an unprecedented tolerance to DMSO, usually required for substrate solubility, and could be immobilized on agarose microbeads through disulfide bonds, via a genetically fused Cystag. This covalent yet reversible binding chemistry showcased the reusability of agarose microbeads in a second round of enzyme immobilization with high reproducibility, reducing waste and increasing the sustainability of the process. Finally, the flow synthesis of a Nelarabine analogue (6‐O‐methyl guanosine) was optimized to full conversion on a 10 mm scale within 2 min residence time, obtaining the highest space‐time yield (89 g L−1 h−1) reported to date. The cost‐efficiency of the system was further enhanced by a catch‐and‐release strategy that allowed to recover and recirculate the excess of sugar donor from the downstream water waste.
Identifying UiO‐67 Metal‐Organic Framework Defects and Binding Sites through Ammonia Adsorption
Authors: Swaroopa Datta Devulapalli Venkata , McDonnell Ryan P. , Ruffley Jonathan P. , Shukla Priyanka B. , Luo Tian‐Yi , De Souza Mattheus L. , Das Prasenjit , Rosi Nathaniel L. , Karl Johnson J. , Borguet Eric
Published: November 2021

Ammonia is a widely used toxic industrial chemical that can cause severe respiratory ailments. Therefore, understanding and developing materials for its efficient capture and controlled release is necessary. One such class of materials is 3D porous metal‐organic frameworks (MOFs) with exceptional surface areas and robust structures, ideal for gas storage/transport applications. Herein, interactions between ammonia and UiO‐67‐X (X: H, NH2, CH3) zirconium MOFs were studied under cryogenic, ultrahigh vacuum (UHV) conditions using temperature‐programmed desorption mass spectrometry (TPD‐MS) and in‐situ temperature‐programmed infrared (TP‐IR) spectroscopy. Ammonia was observed to interact with μ3−OH groups present on the secondary building unit of UiO‐67‐X MOFs via hydrogen bonding. TP‐IR studies revealed that under cryogenic UHV conditions, UiO‐67‐X MOFs are stable towards ammonia sorption. Interestingly, an increase in the intensity of the C−H stretching mode of the MOF linkers was detected upon ammonia exposure, attributed to NH−π interactions with linkers. These same binding interactions were observed in grand canonical Monte Carlo simulations. Based on TPD‐MS, binding strength of ammonia to three MOFs was determined to be approximately 60 kJ mol−1, suggesting physisorption of ammonia to UiO‐67‐X. In addition, missing linker defect sites, consisting of H2O coordinated to Zr4+ sites, were detected through the formation of nNH3⋅H2O clusters, characterized through in‐situ IR spectroscopy. Structures consistent with these assignments were identified through density functional theory calculations. Tracking these bands through adsorption on thermally activated MOFs gave insight into the dehydroxylation process of UiO‐67 MOFs. This highlights an advantage of using NH3 for the structural analysis of MOFs and developing an understanding of interactions between ammonia and UiO‐67‐X zirconium MOFs, while also providing directions for the development of stable materials for efficient toxic gas sorption.
A 1‐GHz GC‐eDRAM in 7‐nm FinFET with static retention time at 700 mV for ultra‐low power on‐chip memory applications
Authors: Seyedzadeh Sany Bahareh , Ebrahimi Behzad
Published: November 2021

Conventional static random‐access memory (SRAM) suffers from high leakage power in advanced complementary metal‐oxide‐semiconductor nodes. Meanwhile, gain‐cell embedded dynamic random‐access memory (GC‐eDRAM) is an area‐efficient alternative to SRAM, although it requires periodic refresh cycles. In this regard, this study proposes a fin field‐effect transistor (FinFET)‐based 5T GC‐eDRAM bitcell that addresses the leakage power issue of SRAM while avoiding the bandwidth‐consuming refreshes of GC‐eDRAM. Furthermore, for the feasibility of scaling down transistors, the gain‐cell design is based on the FinFET, which overcomes short‐channel problems. The proposed 5T bitcell provides additional internal feedback relative to the 4T all‐nMOS fully depleted‐silicon on insulator (FD‐SOI) gain cell to ensure the static retention of both “1” and “0” data. The 2‐kB array was simulated by employing a 7‐nm FinFET predictive technology model (PTM) using HSPICE. The simulation results show that the proposed 5T bitcell (at 0.7 V) enables over 13× smaller data retention power and 10× area reduction compared to the 4T all‐nMOS GC‐eDRAM cell in a 28‐nm FD‐SOI technology.
Geographic variation in the skulls of the horseshoe bats,Rhinolophus simulatorandR. cf. simulator: Determining the relative contributions of adaptation and drift using geometric morphometrics
Authors: Mutumi Gregory L. , Jacobs David S. , Bam Lunga
Published: November 2021

The relative contributions of adaptation and genetic drift to morphological diversification of the skulls of echolocating mammals were investigated using two horseshoe bat species,Rhinolophus simulatorandR. cf. simulator, as test cases. We used 3D geometric morphometrics to compare the shapes of skulls of the two lineages collected at various localities in southern Africa. Size and shape variation was predominantly attributed to selective forces; the between‐population variance (B) was not proportional to the within‐population variance (W). Modularity was evident in the crania ofR. simulatorbut absent in the crania ofR. cf. simulatorand the mandibles of both species. The skulls of the two lineages thus appeared to be under different selection pressures, despite the overlap in their distributions. Difference in the crania ofR. cf. simulatorwas centered largely on the nasal dome region ofR. cf. simulatorbut on the cranium and mandibles ofR. simulator. It is likely that the size and shape of the nasal dome, which acts as a frequency‐dependent acoustic horn, is more crucial inR. cf. simulatorthan inR. simulatorbecause of the higher echolocation frequencies used byR. cf. simulator. A larger nasal dome inR. cf. simulatorwould allow the emission of higher intensity pulses, resulting in comparable detection distances to that ofR. simulator. In contrast, selection pressure is probably more pronounced on the mandibles and cranium ofR. simulatorto compensate for the loss in bite force because of its elongated rostrum. The predominance of selection probably reflects the stringent association between environment and the optimal functioning of phenotypic characters associated with echolocation and feeding in bats.
Spectrum sensing in cognitive radio: A deep learning based model
Authors: Xing Huanlai , Qin Haoxiang , Luo Shouxi , Dai Penglin , Xu Lexi , Cheng Xinzhou
Published: November 2021

Spectrum sensing is an efficient technology for addressing the shortage of spectrum resources. Widely used methods usually employ model‐based features as the test statistics, such as energies and eigenvalues, ignoring the temporal correlation aspect. Deep learning based methods have the potential to focus on various aspects, including temporal correlation. However, the existing ones are not good at capturing the temporal correlation features from spectrum data as traditional convolutional neural network (CNN) and long short‐term memory network (LSTM) are used for feature extraction. Traditional CNNs were not designed to capture the global temporal correlations from time series data. Standard LSTM captures the temporal correlations based on the data collected from previous time slots only and cannot emphasize some important parts of a time series. This article proposes a data‐driven deep learning based model to classify the received raw signals automatically, where the received signal data is considered time‐series data. The proposed deep neural network (DNN) model is mainly featured with 1‐dimensional convolutional neural network (1D CNN), bidirectional long short‐term memory network (BiLSTM), and self‐attention (SA). The 1D CNN and BiLSTM are responsible for extracting the local features and global correlations from the time series data, and BiLSTM could extract sufficient features in opposite directions. The SA layer enables the classifier network to emphasize those important features obtained by BiLSTM. The simulation results demonstrate that our model performs better than a number of existing DNN models in terms of the probabilities of missed detection and false alarm, especially when the signal to noise ratio is low. Moreover, the impacts of the modulation scheme and sample length on the detection performance are studied.
A Negative Feedback Loop and Transcription Factor Cooperation Regulate Zonal Gene Induction by 2, 3, 7, 8‐Tetrachlorodibenzo‐p‐Dioxin in the Mouse Liver
Authors: Yang Yongliang , Filipovic David , Bhattacharya Sudin
Published: November 2021

The cytochrome P450 (Cyp) proteins Cyp1A1 and Cyp1A2 are strongly induced in the mouse liver by the potent environmental toxicant 2, 3, 7, 8‐tetrachlorodibenzo‐p‐dioxin (TCDD), acting through the aryl hydrocarbon receptor (AHR). The induction of Cyp1A1 is localized within the centrilobular regions of the mouse liver at low doses of TCDD, progressing to pan‐lobular induction at higher doses. Even without chemical perturbation, metabolic functions and associated genes are basally zonated in the liver lobule along the central‐to‐portal axis. To investigate the mechanistic basis of spatially restricted gene induction by TCDD, we have developed a multiscale computational model of the mouse liver lobule with single‐cell resolution. The spatial location of individual hepatocytes in the model was calibrated from previously published high‐resolution images. A systems biology model of the network of biochemical signaling pathways underlying Cyp1A1 and Cyp1A2 induction was then incorporated into each hepatocyte in the model. Model simulations showed that a negative feedback loop formed by binding of the induced Cyp1A2 protein to TCDD, together with cooperative gene induction by the β‐catenin/AHR/TCDD transcription factor complex and β‐catenin, help produce the spatially localized induction pattern of Cyp1A1. Although endogenous WNT regulates the metabolic zonation of many genes, it was not a driver of zonal Cyp1A1 induction in our model. Conclusion: In this work, we used data‐driven computational modeling to identify the mechanistic basis of zonally restricted gene expression induced by the potent and persistent environmental pollutant TCDD. The multiscale model and derived results clarify the mechanisms of dose‐dependent hepatic gene induction responses to TCDD. Additionally, this work contributes to our broader understanding of spatial gene regulation along the liver lobule.
Clinical presentation, complications, and outcomes of hospitalized COVID‐19 patients in an academic center with a centralized palliative care consult service
Authors: Baker Sarah M. , Leedy Doug J. , Klafter Jesse Abbott , Zhang Yilin , Secrest Kayla M. , Osborn Tristan R. , Cheng Richard K. , Judson Seth D. , Merel Susan E. , Mikacenic Carmen , Bhatraju Pavan K. , Liles W. Conrad
Published: November 2021

Background and Aims

Palliative care is a critical component of the response of a healthcare system to a pandemic. We present risk factors associated with mortality and highlight an operational palliative care consult service in facilitating early identification of risk factors to guide goal‐concordant care and rational utilization of finite healthcare resources during a pandemic.

Methods

In this case series of 100 consecutive patients hospitalized with COVID‐19, we analyzed clinical data, treatment including palliative care, and outcomes in patients with SARS‐CoV‐2 infection admitted to three hospitals in Seattle, Washington. We compared data between patients who were discharged and non‐survivors.

Results

Age (OR 4.67 [1.43, 15.32] ages 65‐79; OR 3.96 [1.05, 14.89] ages 80‐97), dementia (OR 5.62 [1.60, 19.74]), and transfer from a congregate living facility (OR 5.40 [2.07, 14.07]), as well hypoxemia and tachypnea (OR 7.00 [2.91, 22.41]; OR 2.78 [1.11, 6.97]) were associated with mortality. Forty‐one (41%) patients required intensive care and 22 (22%) invasive mechanical ventilation. Forty‐six (46%) patients were seen by the palliative care service, resulting in a change of resuscitation status in 54% of admitted patients. Fifty‐eight (58%) patients recovered and were discharged, 34 (34%) died, and eight (8%) remained hospitalized, of which seven ultimately survived and one died.

Conclusions

Older age, dementia, and congregate living were associated with mortality. Early discussions of goals of care facilitated by an operational palliative care consult service can effectively guide goal‐concordant care in patients at high risk for mortality during a pandemic. Development of a functional palliative care consult service is an important component of pandemic planning.
The Impact of Chiral Citronellyl‐Functionalization on Indolenine and Anilino Squaraine Thin Films
Authors: Balzer Frank , Schumacher Marvin F. , Mattiello Sara , Schulz Matthias , Zablocki Jennifer , Schmidtmann Marc , Meerholz Klaus , Serdar Sariciftci N. , Beverina Luca , Lützen Arne , Schiek Manuela
Published: November 2021

The impact on chiral aggregation in solution processed and thermally annealed thin films of two indolenine and one anilino squaraines with chiral (S)‐citronellyl functionalization at the nitrogen of the squaraine backbone is investigated. A pseudo polymorphic crystal structure is obtained for one of the indolenine squaraines, but thin films of both compounds are basically non‐aggregated and truly isotropic as evidenced by spectroscopic ellipsometry. The anilino squaraine coalesces and readily aggregates to circular dichroic but discontinuous thin films. The extent of circular dichroism correlates with the morphology of the samples, which is quantified by Mueller matrix polarimetry in combination with atomic force microscopy. The shape of the CD spectra reinforces the hybrid Frenkel and charge‐transfer excitonic nature of the characteristic double hump signatures within unpolarized absorbance spectra of previously investigated non‐chiral anilino squaraines with linear alkyl chain functionalization. Such excitonic CD offers an additional design parameter for next‐generation opto‐electronic devices.
Multi‐party computation mechanism for anonymous equity block trading: A secure implementation of turquoise plato uncross
Authors: Cartlidge John , Smart Nigel P. , Talibi Alaoui Younes
Published: November 2021

Dark pools are financial trading venues where orders are entered and matched in secret so that no order information is leaked. By preventing information leakage, dark pools offer the opportunity for large volume block traders to avoid the costly effects of market impact. However, dark pool operators have been known to abuse their privileged access to order information. To address this issue, we introduce a provably secure multi‐party computation mechanism that prevents an operator from accessing and misusing order information. Specifically, we implement a secure emulation of Turquoise Plato Uncross, Europe's largest dark pool trading mechanism, and demonstrate that it can handle real world trading throughput, with guaranteed information integrity.
A pioneer study on human 3‐nitropropionic acid intoxication: Contributions from metabolomics
Authors: Bendiksen Skogvold Hanne , Yazdani Mazyar , Sandås Elise Mørk , Østeby Vassli Anja , Kristensen Erle , Haarr Dagfinn , Rootwelt Helge , Elgstøen Katja Benedikte Prestø
Published: November 2021

The neurotoxin 3‐nitropropionic acid (3‐NPA) is an inhibitor of succinate dehydrogenase, an enzyme participating both in the citric acid cycle and the mitochondrial respiratory chain. In human intoxications, it produces symptoms such as vomiting and stomach ache in mild cases, and dystonia, coma, and sometimes death in severe cases. We report the results from a liquid chromatography‐Orbitrap mass spectrometry metabolomics study mapping the metabolic impacts of 3‐NPA intoxication in plasma, urine, and cerebrospinal fluid (CSF) samples of a Norwegian boy initially suspected to suffer from a mitochondrial disease. In addition to the identification of 3‐NPA, our findings included a large number of annotated/identified altered metabolites (80, 160, and 62 in plasma, urine, and CSF samples, respectively) belonging to different compound classes, for example, amino acids, fatty acids, and purines and pyrimidines. Our findings indicated protective mechanisms to attenuate the toxic effects of 3‐NPA (e.g., decreased oleamide), occurrence of increased oxidative stress in the patient (such as increased free fatty acids and hypoxanthine) and energy turbulence caused by the intoxication (e.g., increased succinate). To our knowledge, this is the first case of 3‐NPA intoxication reported in Norway and the first published metabolomics study of human 3‐NPA intoxication worldwide. The unexpected identification of 3‐NPA illustrates the importance for health care providers to consider intake‐related intoxications during diagnostic evaluations, treatment and follow‐up examinations for neurotoxicity and a wide range of metabolic derangements.
Structural binding perspectives of common plasticizers and a flame retardant, BDE‐153, against thyroxine‐binding globulin: potential for endocrine disruption
Authors: Sheikh Ishfaq Ahmad , Beg Mohd Amin
Published: November 2021

The human exposure to diverse endocrine‐disrupting chemicals (EDCs) has increased dramatically over several decades with very adverse health effects. Plasticizers and flame retardants constitute important classes of EDCs interfering in endocrine physiology including the thyroid function. Thyroxine (T4) is an important hormone regulating metabolism and playing key roles in developmental processes. In this study, six phthalate and nonphthalate plasticizers and one flame retardant (BDE‐153) were subjected to structural binding against thyroxine‐binding globulin (TBG). The aim was to understand their potential role in thyroid dysfunction using structural binding approach. The structural study was performed using Schrodinger's induced fit docking, followed by binding energy estimations of ligands and the molecular interaction analysis between the ligands and the amino acid residues in the TBG ligand‐binding pocket. The results indicated that all the compounds packed tightly into the TBG ligand‐binding pocket with similar binding pattern to that of TBG native ligand, T4. A high majority of TBG interacting amino acid residues for ligands showed commonality with native ligand, T4. The estimated binding energy values were highest for BDE‐153 followed by nonphthalate plasticizer, DINCH, with values comparable with native ligand, T4. The estimated binding energy values of other plasticizers DEHP, DEHT, DEHA, ATBC, and TOTM were less than DINCH. In conclusion, the tight docking conformations, amino acid interactions, and binding energy values of the most of the indicated ligands were comparable with TBG native ligand, T4, suggesting their potential for thyroid dysfunction. The results revealed highest potential thyroid disruptive action for BDE‐153 and DINCH.