bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recent Updates on Azido‐reductive Cyclization Approaches: Syntheses of aza‐Heterocyclic Frameworks
Authors: Soni Jay Prakash , Kadagathur Manasa , Shankaraiah Nagula 
Published: November 2021

AbstractThe first organic azide (phenyl azide) was synthesized in 1864 and since then, its structure, syntheses, and applications have reaped extreme attention from chemists across the globe. Later, the unambiguous documentation of its linear structure and chemical reactivity led to all‐embracing research in the chemistry of azides. The unique electronic structure and chemical reactivity placed the organic azides at the interface between chemistry, biology, medicine, and material science. In this regard, the reaction of azides where a single‐nitrogen atom is retained was well implemented for the synthesis of natural products and other vital organic frameworks embedding various aza‐heterocyclic skeletons. This review emphasizes the recent applications (2015–2021) of organic azides in the synthesis of the aforementioned organic molecules employing an azido‐reductive cyclization approach with the retention of a single nitrogen atom.
Simulated patterns of mitochondrial diversity are consistent with partial population turnover in Bronze Age Central Europe
Authors: Broccard Nicolas , Silva Nuno Miguel , Currat Mathias 
Published: November 2021

AbstractObjectivesThe analysis of ancient mitochondrial DNA from osteological remains has challenged previous conclusions drawn from the analysis of mitochondrial DNA from present populations, notably by revealing an absence of genetic continuity between the Neolithic and modern populations in Central Europe. Our study investigates how to reconcile these contradictions at the mitochondrial level using a modeling approach.Materials and MethodsWe used a spatially explicit computational framework to simulate ancient and modern DNA sequences under various evolutionary scenarios of post Neolithic demographic events and compared the genetic diversity of the simulated and observed mitochondrial sequences. We investigated which—if any—scenarios were able to reproduce statistics of genetic diversity similar to those observed, with a focus on the haplogroup N1a, associated with the spread of early Neolithic farmers.ResultsDemographic fluctuations during the Neolithic transition or subsequent demographic collapses after this period, that is, due to epidemics such as plague, are not sufficient to explain the signal of population discontinuity detected on the mitochondrial DNA in Central Europe. Only a scenario involving a substantial genetic input due to the arrival of migrants after the Neolithic transition, possibly during the Bronze Age, is compatible with observed patterns of genetic diversity.DiscussionOur results corroborate paleogenomic studies, since out of the alternative hypotheses tested, the best one that was able to recover observed patterns of mitochondrial diversity in modern and ancient Central European populations was one were immigration of populations from the Pontic steppes during the Bronze Age was explicitly simulated.
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

AbstractBackgroundA 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.MethodsA 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.ResultsIn 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.ConclusionAlthough 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

AbstractThere 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

AbstractIntroductionWe 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).MethodsThree 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.ResultsThe 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).DiscussionPE‐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

AbstractIbrutinib 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

AbstractA 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

AbstractSqualene 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

ObjectiveHyperuricemia 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.MethodsStudy 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).ResultsThe 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.ConclusionGut 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

AbstractIn 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

AbstractThis 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

AbstractTransitioning 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

AbstractNow 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

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

ABSTRACTDistance 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.