bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and safety of glycoproteinIIb/IIIainhibitors in addition toP2Y12inhibitors inST‐segment elevation myocardial infarction: A subanalysis of thePOPularGenetics trial
Authors: Tavenier Anne H. , Claassens Daniel M. F. , Hermanides Renicus S. , Vos Gerrit J. A. , Bergmeijer Thomas O. , Kelder Johannes C. , Deneer Vera H. M. , van 't Hof Arnoud W. J. , ten Berg Jurriën M.
Published: July 2021

Background

Glycoprotein IIb/IIIa inhibitors (GPI) are still used in patients with ST‐segment elevation myocardial infarction (STEMI) who undergo primary percutaneous coronary intervention (PCI), although discussion about its clinical benefit is ongoing.

Methods

GPI use was analyzed in this subanalysis of the POPular Genetics trial, which randomized STEMI patients toCYP2C19genotype‐guided treatment (clopidogrel or ticagrelor) or standard treatment with ticagrelor/prasugrel. The composite thrombotic endpoint consisted of cardiovascular death, myocardial infarction (MI), definite stent thrombosis, and stroke at 30 days. The combined bleeding endpoint consisted of Platelet Inhibition and Patient Outcomes (PLATO) major and minor bleeding at 30 days. Univariable and multivariable analyses in addition to a propensity score‐matched (PSM) analysis were conducted.

Results

In total, 2378 patients, of whom 1033 received GPI and 1345 did not, were included. In multivariable analysis, GPI administration was associated with fewer thrombotic events (hazard ratio [HR] 0.22, 95% confidence interval [CI] 0.09–0.55) and MIs (HR 0.24, 95% CI 0.08–0.73). Furthermore, GPI administration was associated with an increase in bleedings (HR 2.02, 95% CI 1.27–3.19), driven by minor bleedings (HR 2.32, 95% CI 1.43–3.76), without a significant difference in major bleedings (HR 0.69, 95% CI 0.19–2.57). In the PSM analysis, no significant association was found.

Conclusion

In STEMI patients undergoing primary PCI, GPI administration was associated with a reduction in thrombotic events at a cost of an increase in (mostly minor) bleedings in multivariable analysis, while propensity score analysis did not show significant associations.
Fluorescent Molecular Logic Gates Driven by Temperature and by Protons in Solution and on Solid
Authors: West Matthew E. S. , Yao Chao‐Yi , Melaugh Gavin , Kawamoto Kyoko , Uchiyama Seiichi , de Silva A. Prasanna
Published: July 2021

Temperature‐driven fluorescent NOT logic is demonstrated by exploiting predissociation in a 1,3,5‐trisubstituted Δ2‐pyrazoline on its own and when grafted onto silica microparticles. Related Δ2‐pyrazolines become proton‐driven YES and NOT logic gates on the basis of fluorescent photoinduced electron transfer (PET) switches. Additional PASS 1 and YES+PASS 1 logic gates on silica are also demonstrated within the same family. Beside these small‐molecule systems, a polymeric molecular thermometer based on a benzofurazan‐derivatized N‐isopropylacrylamide copolymer is attached to silica to produce temperature‐driven fluorescent YES logic.
ChemBead Enabled High‐Throughput Cross‐Electrophile Coupling Reveals a New Complementary Ligand
Authors: Aguirre Ana L. , Loud Nathan L. , Johnson Keywan A. , Weix Daniel J. , Wang Ying
Published: July 2021

High‐throughput experimentation (HTE) methods are central to modern medicinal chemistry. While many HTE approaches to C−N and Csp2−Csp2 bonds are available, options for Csp2−Csp3 bonds are limited. We report here how the adaptation of nickel‐catalyzed cross‐electrophile coupling of aryl bromides with alkyl halides to HTE is enabled by AbbVie ChemBeads technology. By using this approach, we were able to quickly map out the reactivity space at a global level with a challenging array of 3×222 micromolar reactions. The observed hit rate (56 %) is competitive with other often‐used HTE reactions and the results are scalable. A key to this level of success was the finding that bipyridine 6‐carboxamidine (BpyCam), a ligand that had not previously been shown to be optimal in any reaction, is as general as the best‐known ligands with complementary reactivity. Such “cryptic” catalysts may be common and modern HTE methods should facilitate the process of finding these catalysts.
Effect of Sn content on Pt/CNT electrocatalysts for direct ethanol fuel cell application
Authors: Azcoaga Chort M. Florencia , Nagel Pablo A. , Veizaga Natalia S. , Rodríguez Virginia I. , de Miguel Sergio R.
Published: July 2021

Several bimetallic PtSn catalysts supported on multiwalled carbon nanotubes for ethanol electro‐oxidation were prepared by conventional impregnation‐reduction method. The Pt loading was kept at 20 wt.% and Pt:Sn atomic ratios of 5:1, 3:1, and 1:1 were selected. The catalysts were structurally characterized by temperature programmed reduction, X‐ray diffraction, X‐ray photoelectron spectroscopy, H2 chemisorption, cyclohexane dehydrogenation reaction, and transmission electron microscopy. The electrochemical characterization of the electrocatalytic materials was carried out in acid medium by cyclic voltammetry, linear sweep voltammetry, chronoamperometry, and CO stripping techniques. Among the different stoichiometries tested, the Pt(20)Sn(12.17)/CNT catalyst exhibited the highest electrocatalytic activity for ethanol oxidation reaction, with mass current density of 189.5 mA mgPt−1 at 796 mV (vs. Ag/AgCl).
Longitudinal association between cognitive depressive symptoms and D‐dimer levels in patients following acute myocardial infarction
Authors: von Känel Roland , Pazhenkottil Aju P. , Meister‐Langraf Rebecca E. , Znoj Hansjörg , Schmid Jean‐Paul , Zuccarella‐Hackl Claudia , Barth Jürgen , Schnyder Ulrich , Princip Mary
Published: July 2021

Background

A prothrombotic tendency could partially explain the poor prognosis of patients with coronary heart disease and depression. We hypothesized that cognitive depressive symptoms are positively associated with the coagulation activation marker D‐dimer throughout the first year after myocardial infarction (MI).

Methods

Patients with acute MI (mean age 60 years, 85% men) were investigated at hospital admission (n = 190), 3 months (n = 154) and 12 months (n = 106). Random linear mixed regression models were used to evaluate the relation between cognitive depressive symptoms, assessed with the Beck depression inventory (BDI), and changes in plasma D‐dimer levels. Demographics, cardiac disease severity, medical comorbidity, depression history, medication, health behaviors, and stress hormones were considered for analyses.

Results

The prevalence of clinical depressive symptoms (13‐item BDI score ≥ 6) was 13.2% at admission and stable across time. Both continuous (p < .05) and categorical (p < .010) cognitive depressive symptoms were related to higher D‐dimer levels over time, independent of covariates. Indicating clinical relevance, D‐dimer was 73 ng/ml higher in patients with a BDI score ≥ 6 versus those with a score < 6. There was a cognitive depressive symptom‐by‐cortisol interaction (p < .05) with a positive association between cognitive depressive symptoms and D‐dimer when cortisol levels were high (p < .010), but not when cortisol levels were low (p > .05). Fluctuations (up and down) of cognitive depressive symptoms and D‐dimer from one investigation to the next showed also significant associations (p < .05).

Conclusions

Cognitive depressive symptoms were independently associated with hypercoagulability in patients up to 1 year after MI. Hypothalamic–pituitary–adrenal axis could potentially modify this effect.
Comparison of new magnetic resonance imaging grading system with conventional endoscopy for the early detection of nasopharyngeal carcinoma
Authors: Liu Zhiwei , Li Hui , Yu Kelly J. , Xie Shang‐Hang , King Ann D. , Ai Qi‐Yong H. , Chen Wen‐Jie , Chen Xiao‐Xia , Lu Zi‐Jian , Tang Lin‐Quang , Wang Lin , Xie Chuan‐Miao , Ling Wei , Lu Yu‐Qiang , Huang Qi‐Hong , Coghill Anna E. , Fakhry Carole , Pfeiffer Ruth M. , Zeng Yi‐Xin , Cao Su‐Mei , Hildesheim Allan
Published: July 2021

Background

Although stratifying individuals with respect to nasopharyngeal carcinoma (NPC) risk with Epstein‐Barr virus–based markers is possible, the performance of diagnostic methods for detecting lesions among screen‐positive individuals is poorly understood.

Methods

The authors prospectively evaluated 882 participants aged 30 to 70 years who were enrolled between October 2014 and November 2018 in an ongoing, population‐based NPC screening program and had an elevated NPC risk. Participants were offered endoscopy and magnetic resonance imaging (MRI), and lesions were identified either by biopsy at a follow‐up endoscopy or further contact and linkage to the local cancer registry through December 31, 2019. The diagnostic performance characteristics of endoscopy and MRI for NPC detection were investigated.

Results

Eighteen of 28 identified NPC cases were detected by both methods, 1 was detected by endoscopy alone, and 9 were detected by MRI alone. MRI had significantly higher sensitivity than endoscopy for NPC detection overall (96.4% vs 67.9%; Pdifference = .021) and for early‐stage NPC (95.2% vs 57.1%; P = .021). The sensitivity of endoscopy was suggestively lower among participants who had previously been screened in comparison with those undergoing an initial screening (50.0% vs 81.2%; P = .11). The authors observed a higher overall referral rate by MRI versus endoscopy (17.3% vs 9.1%; P < .001). Cases missed by endoscopy had early‐stage disease and were more commonly observed for tumors originating from the pharyngeal recess.

Conclusions

MRI was more sensitive than endoscopy for NPC detection in the context of population screening but required the referral of a higher proportion of screen‐positive individuals. The sensitivity of endoscopy was particularly low for individuals who had previously been screened.
Validation and parameter optimization of a hybrid embedded/homogenized solid tumor perfusion model
Authors: Kremheller Johannes , Brandstaeter Sebastian , Schrefler Bernhard A. , Wall Wolfgang A.
Published: July 2021

The goal of this paper is to investigate the validity of a hybrid embedded/homogenized in‐silico approach for modeling perfusion through solid tumors. The rationale behind this novel idea is that only the larger blood vessels have to be explicitly resolved while the smaller scales of the vasculature are homogenized. As opposed to typical discrete or fully resolved 1D–3D models, the required data can be obtained with in‐vivo imaging techniques since the morphology of the smaller vessels is not necessary. By contrast, the larger vessels, whose topology and structure is attainable noninvasively, are resolved and embedded as one‐dimensional inclusions into the three‐dimensional tissue domain which is modeled as a porous medium. A sound mortar‐type formulation is employed to couple the two representations of the vasculature. We validate the hybrid model and optimize its parameters by comparing its results to a corresponding fully resolved model based on several well‐defined metrics. These tests are performed on a complex data set of three different tumor types with heterogeneous vascular architectures. The correspondence of the hybrid model in terms of mean representative elementary volume blood and interstitial fluid pressures is excellent with relative errors of less than 4%. Larger, but less important and explicable errors are present in terms of blood flow in the smaller, homogenized vessels. We finally discuss and demonstrate how the hybrid model can be further improved to apply it for studies on tumor perfusion and the efficacy of drug delivery.
How to Integrate CYP2D6 Phenoconversion Into Clinical Pharmacogenetics: A Tutorial
Authors: Cicali Emily J. , Elchynski Amanda L. , Cook Kelsey J. , Houder John T. , Thomas Cameron D. , Smith D. Max , Elsey Amanda , Johnson Julie A. , Cavallari Larisa H. , Wiisanen Kristin
Published: July 2021

CYP2D6 genotype is increasingly being integrated into practice to guide prescribing of certain medications. The CYP2D6 drug metabolizing enzyme is susceptible to inhibition by concomitant drugs, which can lead to a clinical phenotype that is different from the genotype‐based phenotype, a process referred to as phenoconversion. Phenoconversion is highly prevalent but not widely integrated into practice because of either limited experience on how to integrate or lack of knowledge that it has occurred. We built a calculator tool to help clinicians integrate a standardized method of assessing CYP2D6 phenoconversion into practice. During tool‐building, we identified several clinical factors that need to be considered when implementing CYP2D6 phenoconversion into clinical practice. This tutorial shares the steps that the University of Florida Health Precision Medicine Program took to build the calculator tool and identified clinical factors to consider when implementing CYP2D6 phenoconversion in clinical practice.
Halide Salt‐Catalyzed Crosslinked Polyurethanes for Supercapacitor Gel Electrolyte Applications
Authors: Wei Chien Sheau , Tay Jacob J. M. , Chee Celestine P. T. , Jun Loh Xian , Fam Derrick W. H. , Lim Jason Y. C.
Published: July 2021

Gel polymer electrolytes are an important advancement in energy storage technology due to their enhanced safety and practical ionic conductivities at ambient temperatures. Herein, a simple one‐step facile synthesis of chemically crosslinked polyurethanes containing polyethylene oxide (PEO) and polypropylene oxide (PPO) macromolecular segments was developed, using ubiquitous non‐toxic tetrabutylammonium or potassium chloride and bromide salts as catalysts. These salts were shown to catalyze the gelation of diol‐diisocyanate polyaddition reactions within minutes. When impregnated with a liquid electrolyte, the resulting gel electrolyte exhibited a practical ionic conductivity of 1.1×10−4 S cm−1 at 40 °C and low segmental chain motion activation energy (11 kJ mol−1). These findings further promote PEO‐PPO polyurethanes as a biocompatible class of materials suitable for further exploration as gel polymer electrolytes for supercapacitors.
Metapopulation dynamics of oysters: sources, sinks, and implications for conservation and restoration
Authors: Theuerkauf Seth J. , Puckett Brandon J. , Eggleston David B.
Published: July 2021

Metapopulation and source–sink dynamics are increasingly considered within spatially explicit management of wildlife populations, yet the application of these concepts has generally been limited to comparisons of the performance (e.g., demographic rates or dispersal) inside vs. outside protected areas, and at spatial scales that do not encompass an entire metapopulation. In the present study, a spatially explicit, size‐structured matrix model was applied to simulate the dynamics of an Eastern oyster (Crassostrea virginica) metapopulation in the second largest estuary in the United States—the Albemarle‐Pamlico Estuarine System in North Carolina. The model integrated larval dispersal simulations with empirical measures of oyster demographic rates to simulate the dynamics of the entire oyster metapopulation consisting of 646 reefs and five reef types: (1) restored subtidal reefs closed to harvest (i.e., sanctuaries or protected areas; n = 14), (2) restored subtidal reefs open to harvest (n = 53), (3) natural subtidal reefs open to harvest (n = 301), (4) natural intertidal reefs open to harvest (n = 129), and (5) oyster reefs on manmade, hard structures such as seawalls (n = 149). Key findings included (1) an overall stable, yet slightly declining oyster metapopulation, (2) variable reef type‐specific population trajectories, largely dependent on spatiotemporal variation in larval recruitment, (3) a greater relative importance of inter‐reef larval connectivity on metapopulation dynamics than local larval retention processes, and (4) spatiotemporal variation in the source–sink status of reef subpopulations wherein subtidal sanctuaries and reefs located in the northeastern portion of the estuary were frequent sources. From a management perspective, continued protection of oyster sanctuaries is warranted. Sanctuaries represented only 6.2% of the total reef area, however, they harbored 19% (± 2%) of all oysters and produced 25% (± 6%) of all larvae settling within the metapopulation. Additional management priorities should focus on restoration or conservation of subpopulations that serve as frequent source subpopulations (including those with poor demographic rates, but high connectivity potential), and management of harvest from sink subpopulations. The application of a source–sink framework and similar integrated modeling approach could inform management of oysters in other systems, as well as other species that exhibit similar metapopulation characteristics.
Axially‐ and Meso‐Substituted Aza‐Crown‐Ether‐Incorporated BIII Subporphyrins: Control of Electron‐Donating Ability by Metal Ion Chelation
Authors: Kise Koki , Lee Yu Jin , Tanaka Takayuki , Kim Dongho , Osuka Atsuhiro
Published: July 2021

A series of subporphyrin‐based fluorescent probes bearing 1‐aza‐15‐crown‐5 or 1‐aza‐18‐crown‐6 moieties at the meso or axial positions were prepared by Pd‐catalyzed Buchwald‐Hartwig amination reaction of the corresponding bromosubporphyrins. Both types of aza‐crown‐ether‐incorporated subporphyrins were fluorescent in solution and exhibited cation‐dependent absorption and fluorescence changes. In fluorescence titration experiments, opposite responses were observed for the two types of subporphyrins. Namely, fluorescence quenching occurred for the meso‐substituted subporphyrins while fluorescence enhancement was observed for the axially‐substituted subporphyrins. These results demonstrate the advantage of subporphyrins being viable to serve as turn‐off‐type or turn‐on‐type fluorescence probes, depending upon substitution pattern.
Using legacy data to reconstruct the past? Rescue, rigour and reuse in peatland geochronology
Authors: Quik Cindy , van der Velde Ype , Harkema Tom , van der Plicht Hans , Quik Jim , van Beek Roy , Wallinga Jakob
Published: July 2021

There is a growing interest in the rescue and reuse of data from past studies (so‐called legacy data). Data loss is alarming, especially where natural archives are under threat, such as peat deposits. Here we develop a workflow for reuse of legacy radiocarbon dates in peatland studies, including a rigorous quality assessment that can be tailored to specific research questions and study regions. A penalty is assigned to each date based on criteria that consider taphonomic quality (i.e., sample provenance) and dating quality (i.e., sample material and method used). The weights of quality criteria may be adjusted based on the research focus, and resulting confidence levels may be used in further analyses to ensure robustness of conclusions. We apply the proposed approach to a case study of a (former) peat landscape in the Netherlands, aiming to reconstruct the timing of peat initiation spatially. Our search yielded 313 radiocarbon dates from the 1950s to 2019. Based on the quality assessment, the dates—of highly diverse quality—were assigned to four confidence levels. Results indicate that peat initiation for the study area first peaked in the Late Glacial (~14,000 cal years BP), dropped during the Boreal (~9,500 cal years BP) and showed a second peak in the Subboreal (~4,500 cal years BP). We tentatively conclude that the earliest peak was mostly driven by climate (Bølling–Allerød interstadial), whereas the second was probably the result of Holocene sea level rise and related groundwater level rise in combination with climatic conditions (hypsithermal). Our study highlights the potential of legacy data for palaeogeographic reconstructions, as it is cost‐efficient and provides access to information no longer available in the field. However, data retrieval may be challenging, and reuse of data requires that basic information on location, elevation, stratigraphy, sample and laboratory analysis are documented irrespective of the original research aims.
On the use of IMU (inertial measurement unit) sensors in geomorphology
Authors: Maniatis Georgios
Published: July 2021

Inertial measurement units (IMUs) are mobile sensors assemblies constructed using a combination of MEMS (micro electrical mechanical systems) accelerometers, gyroscopes and magnetometers. Both the technology and its applications to geomorphic problems are developing rapidly, since they demonstrate the prospect of monitoring individual sediment grains, of various sizes, during transport and at high frequency. This prospect has numerous implications which range from hazard identification and warning to complex theoretical derivations for sediment transport modelling. At the same time, the deployment of IMUs needs to be underpinned by a number of technical considerations regarding the limitations of the technology and the physics of the inertial measurements. IMU measurements should be reported in a manner that allows for clear understanding of the scope of the study, with sufficient detail for repeatability and clear error characterization. At a secondary level, IMU measurements should be linked clearly with the physics of sediment motion. Here the author highlights five technical issues which can lead to the misinterpretation of IMU measurements. His scope is to begin a dialogue towards a collective agreement on a presentation/reporting protocol for IMU measurements in geomorphic studies that will allow for the coherent contextualization of the technology and accelerate its scientific impact within geosciences.
Cannabinoid signaling promotes the de‐differentiation and proliferation of Müller glia‐derived progenitor cells
Authors: Campbell Warren A. , Blum Sydney , Reske Alana , Hoang Thanh , Blackshaw Seth , Fischer Andy J.
Published: July 2021

Endocannabinoids (eCB) are lipid‐based neurotransmitters that are known to influence synaptic function in the visual system. eCBs are also known to suppress neuroinflammation in different pathological states. However, nothing is known about the roles of the eCB system during the transition of Müller glia (MG) into proliferating progenitor‐like cells in the retina. Accordingly, we used the chick and mouse model to characterize expression patterns of eCB‐related genes and applied pharmacological agents to investigate how the eCB system impacts glial reactivity and the capacity of MG to become Müller glia‐derived progenitor cells (MGPCs). We queried single cell RNA‐seq libraries to identify eCB‐related genes and identify cells with dynamic patterns of expression in damaged retinas. MG and inner retinal neurons expressed the eCB receptor CNR1, as well as enzymes involved in eCB metabolism. In the chick, intraocular injections of cannabinoids, 2‐Arachidonoylglycerol (2‐AG) and Anandamide (AEA), stimulated the formation of MGPCs. Cannabinoid Receptor 1 (CNR1)‐agonists and Monoglyceride Lipase‐inhibitor promoted the formation of MGPCs, whereas CNR1‐antagonist and inhibitors of eCB synthesis suppressed this process. In damaged mouse retinas where MG activate NFkB‐signaling, activation of CNR1 decreased and inhibition of CNR1 increased NFkB, whereas levels of neuronal cell death were unaffected. Surprisingly, retinal microglia were largely unaffected by increases or decreases in eCB‐signaling in both chick and mouse retinas. We conclude that the eCB system in the retina influences the reactivity of MG and the formation of proliferating MGPCs, but does not influence the reactivity of immune cells in the retina.
Correlation between peripheral blood automated hematopoietic progenitor cell counts and flow cytometric CD34+ cell counts differs according to diagnosis in patients undergoing autologous peripheral blood stem cell transplantation
Authors: Kim Sang‐Mi , Kim Hyun‐Young , Kim Seok Jin , Jang Jun Ho , Kim Kihyun , Kim Won Seog , Jung Chul Won , Cho Duck , Kang Eun‐Suk
Published: July 2021

Background

An automated hematopoietic progenitor cell count measurement in Sysmex XN analyzer (XN‐HPC) has been developed to assist flow cytometry CD34+ cell count measurement, which requires technical expertise and a long turnaround time. Here, we evaluated the correlation between XN‐HPC count and flow cytometric CD34+ cell count in pre‐harvest peripheral blood (PB) samples from patients undergoing autologous peripheral blood stem cell (PBSC) transplantation according to diagnosis and investigated the possible cause of the decreased correlation in plasma cell neoplasm patients.

Materials and Methods

We retrospectively included 399 patient data that had matched PB XN‐HPC count and CD34+ cell count of PB and apheresis product from Samsung Medical Center (SMC) and the Hematopoietic Stem Cell (HSC) registry. We assessed the diagnostic accuracy and the potential cutoff values of XN‐HPC count for predicting adequate PBSC collection.

Results

The PB XN‐HPC count was 1.6 and 1.3‐fold higher than the CD34+ cell count in SMC (25.0 vs 15.9/μl) and the HSC registry (20.0 vs 15.2/μl), respectively. Overall the correlation between the PB XN‐HPC and CD34+ cell count was moderate (SMC, r = 0.71; HSC registry, r = 0.66). A significant proportional and systemic bias with overestimation of XN‐HPC count were noted in the plasma cell neoplasm patients in both SMC and the HSC registry. However, no significant difference in correlation was observed according to myeloma‐related laboratory parameters in plasma cell neoplasm patients.

Conclusion

Our results suggest that XN‐HPC count should be interpreted cautiously in cancer patients undergoing autologous PBSC transplantation, especially in those with plasma cell neoplasm.
Metacognitive reflection and insight therapy in an inpatient setting: Transforming messianism to a coherent mission
Authors: Cohen‐Chazani Yael , Lysaker Paul H. , Roe David , Hasson‐Ohayon Ilanit
Published: July 2021

Metacognitive reflection and insight therapy (MERIT) is an integrative form of psychotherapy which seeks to help adults with serious mental illness make sense of the psychosocial challenges and possibilities they face and decide how to respond to them and direct their own recovery. In this article, we present an adaptation of MERIT to the context of an inpatient ward with an accompanied case illustration. Specifically, we describe how this approach is supported by a broad intersubjective framework, followed by a presentation of processes and contents of the treatment. Special attention is given to the concurrent improvements in reflective abilities and overall well‐being of the patient. The unique role that psychotherapy in general, and approaches that emphasize reflective processes in particular, play during acute crises in an inpatient setting is discussed.
Genetic counselor experiences with telehealth before and after COVID‐19
Authors: Mills Rachel , MacFarlane Ian M , Caleshu Colleen , Ringler Margaret A , Zierhut Heather A
Published: July 2021

While genetic counselor (GC) utilization of telehealth has increased in recent years, the onset of the COVID‐19 pandemic significantly accelerated the adoption of telehealth for many. We investigated GC experiences with telehealth including perceived advantages, disadvantages, and barriers using a one‐time online survey of GCs who provided direct patient care in recent years. The survey examined experiences with telehealth before and after the onset of COVID‐19. We made broad comparisons to findings from a similar study our research team conducted five years ago. GCs reported an increase in the utilization of telehealth over time, with significant increases from pre‐2017 (44%) to pre‐COVID‐19 (70%) and then to present (87%) (p<.001 and .02, respectively). There was no significant change in the total number of hours worked from pre‐COVID‐19 to the time of survey completion, nor were there significant changes in the amount of time spent on clinical responsibilities or interfacing with patients. However, the total number of hours worked in telehealth significantly increased (z = 5.05, p<.001) as did the percent of time spent interacting with patients via telehealth [t(72)=3.74, p<.001, d = 0.44]. Participants overwhelmingly preferred video (84%) over telephone; this differs from our previous survey where video was the preferred modality for 59% (p<.001). We utilized open‐ended questions to elicit reasons for modality preference. The most‐cited barrier to telehealth utilization was billing/reimbursement issues, with 39% noting this obstacle. This is consistent with our previous study where 30% cited billing/reimbursement as the primary barrier. These findings indicate a need for continued efforts to improve billing and reimbursement for genetic counseling offered via telehealth. They also present an opportunity for additional exploration regarding patient preferences for telehealth modality.
Role of liver transplantation in urea cycle disorders: Report from a nationwide study in Japan
Authors: Kido Jun , Matsumoto Shirou , Häberle Johannes , Inomata Yukihiro , Kasahara Mureo , Sakamoto Seisuke , Horikawa Reiko , Tanemura Akihiro , Okajima Hideaki , Suzuki Tatsuya , Nakamura Kimitoshi
Published: July 2021

Urea cycle disorders (UCDs) are inherited metabolic diseases causing hyperammonemia by defects in urea cycle enzymes or transporters. Liver transplantation (LT) currently is the only curative treatment option until novel therapies become available. We performed a nationwide questionnaire‐based study between January 2000 and March 2018 to investigate the effect of LT in patients with UCDs in Japan. A total of 231 patients with UCDs were enrolled in this study. Of them, a total of 78 patients with UCDs (30 male and 16 female ornithine transcarbamylase deficiency (OTCD), 21 carbamoyl phosphate synthetase 1 deficiency (CPSD), 10 argininosuccinate synthetase deficiency (ASSD) and 1 arginase 1 deficiency (ARGD)) had undergone LT. Concerning the maximum blood ammonia levels at the onset time in the transplanted male OTCD (N = 28), female OTCD (N = 15), CPSD (N = 21) and ASSD (N = 10), those were median 634 (IQR: 277‐1172), 268 (211‐352), 806 (535‐1382), and 628 (425‐957) μmol/L, respectively. The maximum blood ammonia levels in female OTCD were thus significantly lower than in the other UCDs (all P < .01). LT was effective for long‐term survival, prevented recurrent hyperammonemia attack, and lowered baseline blood ammonia levels in patients with UCDs. LT had limited effect for ameliorating neurodevelopmental outcome in patients with severe disease because hyperammonemia at the onset time already had a significant impact on the brain. Patients with ASSD may be more likely to survive without cognitive impairment by receiving early LT despite severe neonatal hyperammonemia ≥ 360 μmol/L. In patients with neonatal onset OTCD or CPSD, there may be additional factors with adverse effects on the brain that are not improved by LT.
Sensory perception of environmental cues as a modulator of aging and neurodegeneration: Insights from Caenorhabditis elegans
Authors: Dixit Anubhuti , Bhattacharya Bidisha
Published: July 2021

Environmental stimuli such as temperature, food, and smell significantly influence the physiology and behavior of animals. Animals are differentially adapted to maintain their internal body functions in response to varied environmental conditions. These external cues are sensed by specialized neurons which are a part of the chemosensory and thermosensory systems. The inability to respond correctly to varied environmental conditions may result in compromised bodily functions and reduced longevity. For example, the ability to sense food is derived from the integrated action of olfactory and gustatory systems. The damage to the olfactory system will affect our decision of palatable food items which in turn can affect the response of the gustatory system, ultimately causing abnormal feeding habits. Recent studies have provided evidence that aging is regulated by sensory perception of environment. Aging is one of the most common causes of various neurodegenerative diseases and the perception of environmental cues is also found to regulate the development of neurodegenerative phenotype in several animal models. However, specific molecular signaling pathways involved in the process are not completely understood. The research conducted on one of the best‐studied animal models of aging, Caenorhabditis elegans, has demonstrated multiple examples of gene–environment interaction at the neuronal level which affects life span. The findings may be useful to identify the key neuronal regulators of aging and age‐related diseases in humans owing to conserved core metabolic and aging pathways from worms to humans.
Transoral Laser Microsurgery for Glottic Cancer in Patients Over 75 Years Old
Authors: Paderno Alberto , Lancini Davide , Bosio Paolo , Del Bon Francesca , Fior Milena , Berretti Giulia , Alparone Marco , Deganello Alberto , Peretti Giorgio , Piazza Cesare
Published: July 2021

Objectives/Hypothesis

Laryngeal squamous cell carcinoma (LSCC) has a non‐negligible incidence in elderly patients. However, there is still no clear indication on the ideal treatment for early‐intermediate glottic LSCC in this specific age group. Both surgical and nonsurgical approaches may be burdened by complications and sequelae that negatively impact patient's health. In this setting, carbon dioxide transoral laser microsurgery (CO2 TOLMS) is a promising minimally invasive treatment option.

Study Design

Retrospective case series in a single tertiary academic institution.

Methods

Patients who underwent CO2 TOLMS for Tis‐T3 glottic LSCC from 1997 to 2017 were reviewed. Demographic, clinical, and tumor characteristics, as well as postoperative complications were recorded. Overall (OS), disease‐specific (DSS), recurrence‐free (RFS), laryngo‐esophageal dysfunction free survivals (LEDFS), and organ preservation (OP) were calculated.

Results

A total of 134 patients (mean age, 80 ± 4 years; median, 79; range, 75–93) were included in the study. Seven lesions were classified as pTis, 65 as pT1a, 22 as pT1b, 35 as pT2, and 5 as pT3. No treatment‐related death was observed. Twenty‐eight (20.9%) patients reported 10 surgical and 19 medical complications. Five‐year OS, DSS, RFS, LEDFS, and OP were 68.9%, 95.4%, 79.5%, 66%, and 92.5%, respectively. Age and comorbidities were associated with OS and LEDFS. Advanced T categories were negatively correlated with OS, DSS, RFS, LEDFS, and OP. Age and comorbidities were not significant risk factors for complications.

Conclusions

CO2 TOLMS can be considered a valuable therapeutic approach for selected Tis‐T3 glottic LSCC even in the elderly given its favorable oncologic outcomes and minimal aggressiveness.

Level of Evidence

4 Laryngoscope, 132:135–141, 2022
Distinct climate driven spatial patterns of frozen soil and vegetation that reflect plant sensitivities across the Tibetan Plateau
Authors: Zhou Bing‐Rong , Wu Liang , Song Ming‐Hua , Zhou Hua‐Kun , Li Yi‐Kang , Wang Min , Zhang Ting‐Jun , Yan Yu‐Qian , Ji Hai‐Juan
Published: July 2021

Earth's cryosphere and biosphere are extremely sensitive to climate changes, and transitions in states could alter the carbon emission rate to the atmosphere. However, little is known about the climate sensitivities of frozen soil and vegetation production. Moreover, how does climate heterogeneity control the spatial patterns of such sensitivities, and influence regional vulnerability of both frozen soil and vegetation production? Such questions are critical to be answered. We compiled long‐time‐series dataset including frozen soil depth (FD), normalized difference vegetation index (NDVI), and temperature and precipitation across Tibetan Plateau to quantify their sensitivities. Results reveal large spatial heterogeneity in FD and NDVI sensitivities. Precipitation alleviated FD sensitivities to warming in the cold northeast zone but accelerated FD sensitivities to precipitation in the warm south and southeast. Meanwhile, the positive warming effect on the NDVI was largely offset by slow increase of precipitation. Areas with high FD decreasing rate were found in northeast, inland, and south and southeast zones. Predominate area across the nine eco‐regions are characterized as medium FD decreasing rate, and are synchronized with positive NDVI response in inland and west Himalayas, but negative in northeast and south and southeast. Precipitation restriction on NDVI would be pronounced in moist south and southeast. Our study provides new information that makes a much‐needed contribution to advancing our understandings of the effects of global climate change on cryosphere and biosphere, which has important implications for global climate and our ability to predict, and therefore prepare for, future global climatic changes. Our attempt confirms that the method we used could be used to identify climate sensitivity of permafrost based on substantial observation data on active layer dynamics in future.
A case‐study on history and rates of gully erosion in Northeast China
Authors: Wen Yanru , Kasielke Till , Li Hao , Zepp Harald , Zhang Bin
Published: July 2021

Mollisols are of major importance for food security worldwide but are increasingly degraded by soil erosion. Mollisols in Northeast China have been converted into agricultural use only since the 19th century, but gullies are widely distributed. Gully erosion history, rates, and causes in this region remained unclear. We chose a study area with landforms and land‐use history typical for the central Mollisol region of Northeast China to estimate the initiation years and rates of gully erosion from 1968 to 2018 using aerial and satellite imageries. The outlet fan deposits of a large gully system were dated by Cesium‐137 (137Cs) and artifacts. Local farmers were interviewed to verify the results. Gully volumes were measured by a structure‐from‐motion technique using photos taken from an unmanned aerial vehicle. Our results showed that gully systems had already appeared on the steep slopes and along unpaved roads in 1968. They had become larger and more complex in 2018 by the upslope retreat of the main gullies and side gully formation. Gully incision started in the 1950s and 1960s when the original grassland and forest were completely converted into arable land. From 1968 to 2018, the gully density increased from 1.2 to 2.3 km km−2 and the gully heads retreated at speeds from 1.5 to 2.5 m yr−1. The soil loss from gully erosion ranged from 25.7 to 44.7 Mg yr−1 ha−1. These data demonstrate the severity of gully erosion in the Mollisol region of Northeast China and underline the importance of appropriate countermeasures.
Immediate and short‐term effects of Gufoni and Appiani liberatory maneuver for treatment of ageotropic horizontal canal benign paroxysmal positional vertigo: A prospective randomized trial
Authors: Lee Jiyeon , Lee Dong‐Han , Noh Haemin , Shin Jung Eun , Kim Chang‐Hee
Published: July 2021

Objective

To examine the treatment effects of repositioning maneuvers with the head turned 45° downwards (Gufoni maneuver) and 45° upwards (Appiani maneuver) in 25 patients with ageotropic horizontal semicircular canal (HSCC) benign paroxysmal positional vertigo (BPPV).

Methods

Patients were randomly assigned to the Gufoni or Appiani maneuvers, and their immediate and short‐term efficacy was investigated.

Results

The immediate treatment response was successful in four of 16 patients who were treated with the Appiani maneuver and were not successful in any of the nine patients treated with the Gufoni maneuver. The patients who showed spontaneous resolution during follow‐up outnumbered the patients who showed resolution of ageotropic HSCC BPPV immediately after the repositioning maneuvers.

Conclusion

This study showed a very low immediate resolution rate of ageotropic HSCC BPPV after the Gufoni maneuver; this may be attributed to the less effectiveness of the Gufoni maneuver against debris that often exists in the canal side of the cupula. Another interesting finding was that the rate of spontaneous resolution during the follow‐up period was higher than that of immediate resolution after the repositioning maneuvers, which may support the recently proposed hypothesis that ageotropic positional nystagmus can also be evoked by causes other than the otolithic attachment on the cupula, such as a slight change in the biochemical composition of the inner ear fluids.

Level of Evidence

3.
Numerical and Experimental Demonstration of Intermodal Dispersive Wave Generation
Authors: Lüpken Niklas M. , Timmerkamp Maximilian , Scheibinger Ramona , Schaarschmidt Kay , Schmidt Markus A. , Boller Klaus‐J. , Fallnich Carsten
Published: July 2021

Evidence of intermodal dispersive wave generation mediated by intermodal cross‐phase modulation (iXPM) between different transverse modes during supercontinuum generation in silicon nitride waveguides is presented. The formation of a higher‐order soliton in one strong transverse mode leads to phase modulation of a second, weak transverse mode by iXPM. The phase modulation enables not only supercontinuum generation but also dispersive wave generation within the weak mode, that otherwise has insufficient power to facilitate dispersive wave formation. The nonlinear frequency conversion scheme presented here suggests phase‐matching conditions beyond what is currently known, which can be exploited for extending the spectral bandwidth within supercontinuum generation.
Collaborative conversations during the time of COVID‐19: Building a “meta”‐learning community
Authors: Ferguson Lisa , Rentes Victor C. , McCarthy Lauren , Vinson Alexandra H.
Published: July 2021

Problem

COVID‐19 created new research, clinical, educational, and personal challenges, while simultaneously separating work teams who were under work‐from‐home restrictions. Addressing these challenges required new forms of collaborative groups.

Approach

To support the department community and the rapid sharing of new research, educational, clinical, and personal efforts, a Core Team from the Department of Learning Health Sciences at the University of Michigan developed a meeting series called the COVID Conversations. This Experience Report shares the organizational structure of the COVID Conversations, proposes a comparison to traditional Learning Communities, and reports the results of a questionnaire that gathered details about department members' COVID‐related activities.

Outcomes

We identify and describe salient similarities and differences between the COVID Conversations and the characteristics of Learning Communities. We also developed and piloted a taxonomy for characterizing LHS research projects that may be further developed for use in Learning Community planning, in conjunction with other maturity grids and ontologies. We propose the term “Meta‐Learning Community” to describe the structure and function of the COVID Conversations.

Next Steps

In academic medicine, remote work, telemedicine, and virtual learning may be here to stay. The COVID Conversations constitute a distinct and innovative form of collaborative work in which separate teams addressing distinct goals, yet sharing a common passion to tackle the issues brought by the pandemic, are able to share experiences and learn from one other. The challenges of COVID‐19 have made evident the need for multiple forms of organizing teamwork, and our study contributes the notion of a “Meta”‐Learning Community as a new form of collaborative work.
Enzymatic Synthesis of Polyesters and Their Bioapplications: Recent Advances and Perspectives
Authors: Hevilla Víctor , Sonseca Agueda , Echeverría Coro , Muñoz‐Bonilla Alexandra , Fernández‐García Marta
Published: July 2021

This article reviews the most important advances in the enzymatic synthesis of polyesters. In first place, the different processes of polyester enzymatic synthesis, i.e., polycondensation, ring opening, and chemoenzymatic polymerizations, and the key parameters affecting these reactions, such as enzyme, concentration, solvent, or temperature, are analyzed. Then, the latest articles on the preparation of polyesters either by direct synthesis or via modification are commented. Finally, the main bioapplications of enzymatically obtained polyesters, i.e., antimicrobial, drug delivery, or tissue engineering, are described. It is intended to point out the great advantages that enzymatic polymerization present to obtain polymers and the disadvantages found to develop applied materials.
Past and future drought trends, duration, and frequency in the semi‐arid Urmia Lake Basin under a changing climate
Authors: Mirgol Behnam , Nazari Meisam , Etedali Hadi Ramezani , Zamanian Kazem
Published: July 2021

Although the Urmia Lake has undergone remarkable drought conditions within the past decades mainly due to climate change, drought studies covering the entire Urmia Lake Basin and all drought aspects are lacking. The present study investigated the spatial and temporal drought conditions in the Urmia Lake Basin for the past (1988–2017) and future (2021–2050 and 2051–2080) periods using five general circulation models (GCMs) under the IPCC (Intergovernmental Panel on Climate Change) scenarios RCP 2.6, RCP 4.5, and RCP 8.5. The standardized precipitation index (SPI) and standardized precipitation and evapotranspiration index (SPEI) were compared. The SPEI predicted more drought events than the SPI, and it seemed to be a more suitable drought index than the SPI for the basin. In general, the future periods would encounter less drought conditions in terms of significant drought trends and duration than the observed period under all scenarios, but the frequency of quarterly severe drought events in the future periods would be higher than in the observed period. Furthermore, the stations Urmia (western bank) and Tabriz and Maragheh (eastern banks) would face the highest frequency of different types of quarterly drought events in the future periods compared with the observed period. The predicted high frequencies of drought events for the future periods can intensify the current low water level situation of the Urmia Lake, which seriously threatens all types of ecosystems in the basin. Therefore, serious actions need to be taken into account for efficient ecosystem and water resources management in the basin.
A local multi‐transmit coil combined with a high‐density receive array for cerebellar fMRI at 7 T
Authors: Priovoulos Nikos , Roos Thomas , Ipek Özlem , Meliado Ettore F. , Nkrumah Richard O. , Klomp Dennis W. J. , van der Zwaag Wietske
Published: July 2021

The human cerebellum is involved in a wide array of functions, ranging from motor control to cognitive control, and as such is of great neuroscientific interest. However, its function is underexplored in vivo, due to its small size, its dense structure and its placement at the bottom of the brain, where transmit and receive fields are suboptimal. In this study, we combined two dense coil arrays of 16 small surface receive elements each with a transmit array of three antenna elements to improve BOLD sensitivity in the human cerebellum at 7 T. Our results showed improved B1+ and SNR close to the surface as well as g‐factor gains compared with a commercial coil designed for whole‐head imaging. This resulted in improved signal stability and large gains in the spatial extent of the activation close to the surface (<3.5 cm), while good performance was retained deeper in the cerebellum. Modulating the phase of the transmit elements of the head coil to constructively interfere in the cerebellum improved the B1+, resulting in a temporal SNR gain. Overall, our results show that a dedicated transmit array along with the SNR gains of surface coil arrays can improve cerebellar imaging, at the cost of a decreased field of view and increased signal inhomogeneity.