bluuebunny/crossref_metadata_2025 huggingface dataset:
Enabling simulation of high‐dimensional micro‐macro biophysical models through hybrid CPU and multi‐GPU parallelism
Authors: Cook Steven , Shinar Tamar
Published: April 2021

Micro‐macro models provide a powerful tool to study the relationship between microscale mechanisms and emergent macroscopic behavior. However, the detailed microscopic modeling requires tracking and evolving a potentially high‐dimensional configuration space at high computational cost. In this work, we present a novel parallel algorithm for simulating a high‐dimensional micro‐macro model of a gliding motility assay. We utilize a holistic approach aligning the data residency and simulation scales with the hybrid CPU and multi‐GPU hardware. Our novel approach achieves a speedup factor of 9.25× over previous GPU‐accelerated micro‐macro methods on the same hardware. Furthermore, by decoupling dependencies in the microstructure update, we are able to efficiently distribute the microstructure over multiple GPUs with minimal overhead. We test on up to four GPUs and observe excellent scaling, suggesting that significant further speedups are achievable with additional GPUs. Our approach enables micro‐macro simulations of higher complexity and resolution than would otherwise be feasible.
Polynomial algorithms for computing the isolated toughness of interval and split graphs
Authors: Li Fengwei , Ye Qingfang , Broersma Hajo , Zhang Xiaoyan
Published: April 2021

The isolated toughness of a noncomplete graph G is defined as: , where C(G) is the collection of all vertex cutsets of G and i(G − Y) stands for the number of isolated vertices in G − Y. If G is a complete graph, we set . This isolated toughness parameter is closely related to the existence of factors and fractional factors in graphs. These factors and fractional factors are well‐studied within graph theory, and have various applications in several fields related to computer science. In this article, we pay our attention to the computational complexity of computing the isolated toughness. We present polynomial algorithms for computing the exact value of for interval graphs and for split graphs, two well‐studied special graph classes.
Arylethynyl Helices Supported by π‐Stacking and Halogen Bonding
Authors: Bowling Nathan P. , Speetzen Erin D. , Bosch Eric
Published: April 2021

Co‐crystallization of a pyridyl‐containing arylethynyl (AE) moiety with 1,4‐diiodotetrafluorobenzene leads to unique, figure‐eight shaped helical motifs within the crystal lattice. A slight twist in the AE backbone allows each AE unit to simultaneously interact with haloarene units that are stacked on top of one another. Left‐handed (M) and right‐handed (P) helices are interspersed in a regular pattern throughout the crystal. The major driving forces for assembly are 1) halogen bonding between the pyridyl nitrogen atoms and the iodine substituents of the haloarene, with N⋅⋅⋅I distances between 2.81 and 2.84 Å, and 2) π‐π stacking of the haloarenes, with distances of approximately 3.57 Å between centroids. Halogen bonding and π‐π stacking not only work in concert, but also seem to mutually enhance one another. Calculations suggest that the presence of π‐π stacking modestly intensifies the halogen bonding interaction by <0.2 kcal/mol; likewise, halogen bonding to the haloarene enhances the π‐π stacking interaction by 0.59 kcal/mol.
A Disease Progression Model to Quantify the Nonmotor Symptoms of Parkinson’s Disease in Participants With Leucine‐Rich Repeat Kinase 2 Mutation
Authors: Ahamadi Malidi , Mehrotra Nitin , Hanan Nathan , Lai Yee Ka , Gheyas Ferdous , Anton Judith , Bani Massimo , Boroojerdi Babak , Smit Hans , Weidemann Jonas , Macha Sreeraj , Thuillier Vincent , Chen Chao , Yang Minhua , Williams‐Gray Caroline H. , Stebbins Glenn T. , Pagano Gennaro , Hang Yaming , Marek Kenneth , Venuto Charles S. , Javidnia Monica , Dexter David , Pedata Anne , Stafford Bob , Akalu Mussie , Stephenson Diane , Romero Klaus , Sinha Vikram ,   the Critical Path for Parkinson’s Consortium
Published: April 2021

Leucine‐rich repeat kinase 2 (LRRK2) inhibitors are currently in clinical development as interventions to slow progression of Parkinson’s disease (PD). Understanding the rate of progression in PD as measured by both motor and nonmotor features is particularly important in assessing the potential therapeutic effect of LRRK2 inhibitors in clinical development. Using standardized data from the Critical Path for Parkinson’s Unified Clinical Database, we quantified the rate of progression of the Movement Disorder Society–sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS‐UPDRS) Part I (nonmotor aspects of experiences of daily living) in 158 participants with PD who were carriers and 598 participants with PD who were noncarriers of at least one of three different LRRK2 gene mutations (G2019S, R1441C/G, or R1628P). Age and disease duration were found to predict baseline disease severity, while presence of at least one of these three LRRK2 mutations was a predictor of the rate of MDS‐UPDRS Part I progression. The estimated progression rate in MDS‐UPDRS Part I was 0.648 (95% confidence interval: 0.544, 0.739) points per year in noncarriers of a LRRK2 mutation and 0.259 (95% confidence interval: 0.217, 0.295) points per year in carriers of a LRRK2 mutation. This analysis demonstrates that the rate of progression based on MDS‐UPDRS Part I is ~ 60% lower in carriers as compared with noncarriers of LRRK2 gene mutations.
If they don't care, I won't share: Feeling unrelated to one's in‐group increases selfishness instead of behavior for the greater good
Authors: Klein Sina A. , Rudert Selma C.
Published: April 2021

Individuals cooperate more with others to whom they feel connected. As a consequence, reduced belonging to an in‐group decreases cooperation with this group, but not with others. Sometimes, however, there may be no new group available to (re)affiliate with. In this case, reduced belonging may either increase cooperation on a higher level, such as with the superordinate group humanity, or increase selfishness. We investigate this in an online experiment and a survey study. Study 1 (N = 299) showed that being ostracized in Cyberball reduced cooperation with the ostracizers and increased selfish behavior, while cooperation with humanity did not increase. Similarly, Study 2 (N = 1300) showed that lower feelings of belonging were associated with more selfishness, as fewer participants decided to donate to a humanitarian cause. These findings highlight the importance of inclusion and integration for societies and communities who wish to maintain a high level of cooperation.
What activities of daily living at discharge affect the discharge destination of patients in an acute‐care hospital in Japan: A retrospective factor analysis
Authors: Tachi Tomoya , Otsubo Manami , Toyoshima Manabu , Katsuno Hayato , Ueno Anri , Noguchi Yoshihiro , Aoyama Satoshi , Yasuda Masahiro , Mizui Takashi , Goto Chitoshi , Teramachi Hitomi
Published: April 2021

It is important to clarify the influence of activities of daily living (ADL) at discharge on the discharge destination of hospitalised patients. The Functional Independence Measure (FIM) is a widely used ADL assessment scale. In this retrospective study, we aimed to identify what ADL based on FIM at discharge affect the discharge destination of hospitalised patients in an acute‐care hospital, in addition to how nutritional status and the number of drugs used, as well as types of disease, affect discharge‐to‐home. We surveyed age, sex, disease type, length of hospital stay, discharge destination, FIM score at discharge, serum albumin level, and the number of continued drugs in hospitalised patients who underwent rehabilitation in Gifu Municipal Hospital (Gifu, Japan) between January 2014 and December 2014. Multiple logistic regression analysis was performed with discharge to home as a dependent variable and age, sex, disease, FIM score and polypharmacy as independent variables. Multiple logistic regression analysis indicated that a significantly high percentage of discharged‐to‐home patients were associated with ‘self‐care’ (≥33 points; OR: 2.03), ‘sphincter control’ (≥14 points; OR: 1.49), ‘transfers’ (≥13 points; OR: 1.94), and ‘locomotion’ (≥7 points; OR: 3.55), among others. High FIM sub‐scale scores at discharge for self‐care, sphincter control, transfers, and locomotion were clarified as factors associated with discharge‐to‐home. These findings of the association of ADL based on FIM and discharge destination would be useful in deciding discharge destinations for patients in an acute‐phase hospital.
How far can we forecast? Statistical tests of the predictive content
Authors: Breitung Jörg , Knüppel Malte
Published: April 2021

We develop tests for the null hypothesis that forecasts become uninformative beyond some maximum forecast horizon h∗. The forecast may result from a survey of forecasters or from an estimated parametric model. The first class of tests compares the mean‐squared prediction error of the forecast to the variance of the evaluation sample, whereas the second class of tests compares it with the mean‐squared prediction error of the recursive mean. We show that the forecast comparison may easily be performed by adopting the encompassing principle, which results in simple regression tests with standard asymptotic inference. Our tests are applied to forecasts of macroeconomic key variables from the survey of Consensus Economics. The results suggest that these forecasts are barely informative beyond two to four quarters ahead.
Dental hygiene student attitudes about benefits of baccalaureate degree and factors impacting entry‐level program choice
Authors: Reid Heather L. , Boyd Linda D. , Vineyard Jared
Published: April 2021

Purpose/objectives

Although the bachelor's degree is the entry‐level degree option supported by the American Dental Hygienists’ Association, the majority of dental hygiene programs remain associate degree. The aim of this study was to explore factors impacting entry‐level program choice and examine attitudes and perceptions of dental hygiene students pertaining to a bachelor's degree (BS) as the entry‐level degree.

Methods

A cross‐sectional survey research design was utilized with a convenience sample of dental hygiene students (n = 429) from the United States and Canada. The 33‐item survey had four sections: demographics, factors influencing program choice, attitudes, and perceptions of a BS. Descriptive and inferential analysis was used to explore the relationship between variables.

Results

The completion rate was 91% (n = 384). Factors that most influenced program choice included: location (74%), cost (68%), and time to completion (47.7%). Students with mothers who graduated from college were more likely to rank time to completion as their number one factor (37%) (χ2[df2] = 19.6, p < 0.001, phi = 0.33). Students in bachelor's programs were significantly more likely to believe a bachelor's degree better prepared clinicians for duties required in future practice and that the entry‐level degree should be raised to a bachelor's degree (p < 0.001). While more students in associate degree program agreed there were opportunities in education without a bachelor's degree (p < 0.05).

Conclusion

Cost, time to completion, and location were the factors influencing students’ program choice. While the dental hygiene profession advocates raising the entry‐level degree to a bachelor's programs, less than 40% of dental hygiene students supported this change.
Silica sulfuric acid mediated synthesis of naphtho[2,1‐b]furan derivatives and development of one‐pot multicomponent synthesis of substituted pyrazole derivatives
Authors: Uppalapati Divya Sree , Dachuru Rama Sekhara Reddy , Sunkara Satya Veni
Published: April 2021

Silica sulfuric acid (SSA) mediated synthesis of naphtho[2,1‐b]furan derivatives starting from β‐nitrostyrene derivatives and β‐naphthol derivatives under solvent‐free conditions have been developed. The scope of SSA as a heterogeneous catalyst is extended to one‐pot multicomponent reaction for the synthesis of functionalized pyrazole derivatives under solvent‐free conditions from readily available β‐nitrostyrene derivatives, acetyl acetone, and hydrazine hydrate. The synthetic methods have significant advantages such as solvent‐free conditions, simple operation, shorter reaction times, ease and clean isolation procedures, and very good yields of products.
Tissue Probability Based Registration of Diffusion‐Weighted Magnetic Resonance Imaging
Authors: Malovani Cfir , Friedman Naama , Ben‐Eliezer Noam , Tavor Ido
Published: April 2021

Background

Current registration methods for diffusion‐MRI (dMRI) data mostly focus on white matter (WM) areas. Recently, dMRI has been employed for the characterization of gray matter (GM) microstructure, emphasizing the need for registration methods that consider all tissue types.

Purpose

To develop a dMRI registration method based on GM, WM, and cerebrospinal fluid (CSF) tissue probability maps (TPMs).

Study Type

Retrospective longitudinal study.

Population

Thirty‐two healthy participants were scanned twice (legacy data), divided into a training‐set (n = 16) and a test‐set (n = 16), and 35 randomly‐selected participants from the Human Connectome Project.

Field Strength/Sequence

3.0T, diffusion‐weighted spin‐echo echo‐planar sequence; T1‐weighted spoiled gradient‐recalled echo (SPGR) sequence.

Assessment

A joint segmentation‐registration approach was implemented: Diffusion tensor imaging (DTI) maps were classified into TPMs using machine‐learning approaches. The resulting GM, WM, and CSF probability maps were employed as features for image alignment. Validation was performed on the test dataset and the HCP dataset. Registration performance was compared with current mainstream registration tools.

Statistical Tests

Classifiers used for segmentation were evaluated using leave‐one‐out cross‐validation and scored using Dice‐index. Registration success was evaluated by voxel‐wise variance, normalized cross‐correlation of registered DTI maps, intra‐ and inter‐subject similarity of the registered TPMs, and region‐based intra‐subject similarity using an anatomical atlas. One‐way ANOVAs were performed to compare between our method and other registration tools.

Results

The proposed method outperformed mainstream registration tools as indicated by lower voxel‐wise variance of registered DTI maps (SD decrease of 10%) and higher similarity between registered TPMs within and across participants, for all tissue types (Dice increase of 0.1–0.2; P < 0.05).

Data Conclusion

A joint segmentation‐registration approach based on diffusion‐driven TPMs provides a more accurate registration of dMRI data, outperforming other registration tools. Our method offers a “translation” of diffusion data into structural information in the form of TPMs, allowing to directly align diffusion and structural images.

Level of Evidence: 1

Technical Efficacy Stage: 1
Noncontrast‐Enhanced MR‐Based Conductivity Imaging for Breast Cancer Detection and Lesion Differentiation
Authors: Suh June , Kim Jun‐Hyeong , Kim Soo‐Yeon , Cho Nariya , Kim Dong‐Hyun , Kim Rihyeon , Kim Eun Sil , Jang Myoung‐jin , Ha Su Min , Lee Su Hyun , Chang Jung Min , Moon Woo Kyung
Published: April 2021

Background

There is increasing interest in noncontrast‐enhanced MRI due to safety concerns for gadolinium contrast agents.

Purpose

To investigate the clinical feasibility of MR‐based conductivity imaging for breast cancer detection and lesion differentiation.

Study Type

Prospective.

Subjects

One hundred and ten women, with 112 known cancers and 17 benign lesions (biopsy‐proven), scheduled for preoperative MRI.

Field Strength/Sequence

Non‐fat‐suppressed T2‐weighted turbo spin‐echo sequence (T2WI), dynamic contrast‐enhanced MRI and diffusion‐weighted imaging (DWI) at 3T.

Assessment

Cancer detectability on each imaging modality was qualitatively evaluated on a per‐breast basis: the conductivity maps derived from T2WI were independently reviewed by three radiologists (R1–R3). T2WI, DWI, and pre‐operative digital mammography were independently reviewed by three other radiologists (R4–R6). Conductivity and apparent diffusion coefficient (ADC) measurements (mean, minimum, and maximum) were performed for 112 cancers and 17 benign lesions independently by two radiologists (R1 and R2). Tumor size was measured from surgical specimens.

Statistical Tests

Cancer detection rates were compared using generalized estimating equations. Multivariable logistic regression analysis was performed to identify factors associated with cancer detectability. Discriminating ability of conductivity and ADC was evaluated by using the areas under the receiver operating characteristic curve (AUC).

Results

Conductivity imaging showed lower cancer detection rates (20%–32%) compared to T2WI (62%–71%), DWI (85%–90%), and mammography (79%–88%) (all P < 0.05). Fatty breast on MRI (odds ratio = 11.8, P < 0.05) and invasive tumor size (odds ratio = 1.7, P < 0.05) were associated with cancer detectability of conductivity imaging. The maximum conductivity showed comparable ability to the mean ADC in discriminating between cancers and benign lesions (AUC = 0.67 [95% CI: 0.59, 0.75] vs. 0.84 [0.76, 0.90], P = 0.06 (R1); 0.65 [0.56, 0.73] vs. 0.82 [0.74, 0.88], P = 0.07 (R2)).

Data Conclusion

Although conductivity imaging showed suboptimal performance in breast cancer detection, the quantitative measurement of conductivity showed the potential for lesion differentiation.

Evidence Level

1

Technical Efficacy

Stage 2
Historical trends in the trade wind inversion in the tropical North Atlantic Ocean and Caribbean
Authors: Ramseyer Craig A. , Miller Paul W.
Published: April 2021

The trade wind inversion (TWI) serves as an important stabilizing mechanism in the tropical North Atlantic (TNA) region, including the Caribbean basin. Previous studies have diagnosed the TWI using in situ observations and radiosondes, typically over tropical islands. However, studies relying on these point measurements are unable to discern the climatology and evolution of the TWI over the rest of the TNA. This study addresses this gap in the literature through the use of high‐resolution ERA5 reanalysis model level data. Due to the advances in the ERA line of reanalysis products, ERA5 now provides vertical level resolution as fine as ~4 mb in the lower troposphere, enabling the identification of shallow inversions, such as the TWI, consistently on a climatological time scale in remote regions of the world. While still coarser than observed soundings, this reanalysis‐based approach provides a first attempt in understanding TNA TWI variability and its strength and frequency trends from 1979 to 2019. The TWI climatology constructed here finds consilience with previous modelling and observational studies in terms of the spatial variability of the TWI base and strength across this domain. Stronger and more frequent TWIs are noted across the central TNA across all seasons. Results from a Mann–Kendall analysis reveals increasing trends in TWI frequency and strength that vary spatially across the domain based on season. The most widespread and strongest increasing TWI frequency and strength signal is over the central TNA from December to July. Due to the regionalization of trends noted, potential regional forcing mechanisms responsible for these changes are discussed.
Defective cuprous oxide as a selective surface‐enhanced Raman scattering sensor of dye adulteration in Chinese herbal medicines
Authors: Jiang Yuxiao , Cong Shan , Song Ge , Sun Hongzhao , Zhang Wei , Yao Weirong , Zhao Zhigang
Published: April 2021

Chinese herbal medicine is an ancient part of humanity's heritage. However, the quality of commercial Chinese herbal remedies is currently compromised by illegal dyeing and adulteration. A rapid screening method of suspected dyeing compounds based on surface‐enhanced Raman scattering (SERS) has proven difficult to develop due to the extreme complexity of the extraction of traditional Chinese medicinal products, as well as the lack of selective signal enhancement for target adulterants on commercially available Ag or Au substrates. Defective Cu2O nanostructures provide specific anchoring sites for dye adulterants such as Sudan red dyes on the basis of coordination between hydroxyl/azo groups and exposed Cu sites. This coordination facilitates an effective analyte–substrate charge‐transfer, resulting in a prominent Raman signal enhancement for the analyte. Based on the mechanism of selective signal enhancement on Cu2O, this study shows that the adulterant Sudan red III in the extractions of various herbal medicines can be detected directly even at an extremely low concentration of 0.3 mg/kg. The findings suggest the advantages of semiconducting materials as promising SERS substrates for practical applications.
Postoperative duration of opioid use and acute healthcare services use in cancer patients hospitalized for thoracic surgery
Authors: Kurteva Siyana , Tamblyn Robyn , Khosrow‐Khavar Farzin , Meguerditchian Ari N.
Published: April 2021

Background

Postoperative pain control is an important cancer care component. However, opioid consumption has resulted in a surge of adverse events, with thoracic surgery patients having the highest rate of persistent use. The effect of opioid duration post‐discharge and the risk of increased acute healthcare use in this population remains unclear.

Methods

A prospective cohort of non‐metastatic cancer patients was assembled from an academic health center in Montreal (Canada). Clinical data linked to administrative claims from the universal healthcare program was used to determine the association between time‐varying opioid patterns and emergency department (ED) visits/re‐admissions/death 3 months following thoracic surgery.

Results

Of the 610 patients, 77% had at least one opioid dispensed post‐discharge. Compared to non‐opioid users, <15 days of use was associated with a 42% decreased risk of acute healthcare events, adjusted HR 0.58, 95% CI (0.40–0.85); longer durations were not associated with an increased risk. Compared to short‐term use (<15 days), use of >30 days was associated with a 72% increased risk of the outcome, aHR: 1.72, 95% CI (1.01–2.93).

Conclusion

There was a variation in the risk of acute healthcare use associated with postsurgical opioid use. Findings from this study may be used to inform postoperative prescribing practices.
Superior Laryngeal Nerve Block for Treatment of Neurogenic Cough
Authors: Duffy James R. , Litts Juliana K. , Fink Daniel S.
Published: April 2021

Objectives

This study aimed to add to the body of evidence for efficacy of Superior Laryngeal Nerve (SLN) blocks for treatment of neurogenic cough. Efficacy at short‐ and long‐term intervals are presented as well as relationships with laryngoscopic findings.

Methods

A retrospective chart review of patients treated with SLN block between 2018 and 2020 was conducted. Patient demographics, videostroboscopic findings, and patient‐subjective perception of outcomes were recorded and analyzed. Cough Severity Index (CSI) scores from pre‐injection, short‐term follow‐up, and long‐term follow‐up were compared.

Results

Twenty patients underwent SLN block in the clinic setting. Four patients were excluded for incomplete records. The indication was neurogenic cough refractory to medical management and/or cough suppression therapy. Patients with short‐term follow‐up (n = 13) had statistically significant decrease in CSI scores, with a mean baseline CSI of 24.3 decreasing to 16.15 (P = .006). Patients with evidence of Vocal Fold Motion/Vibratory Abnormalities (VFA) (n = 8) showed improvement in short‐term CSI scores, with a mean baseline CSI of 24.13 decreasing to 14.5 (P = .004). Those without evidence of VFA did not have statistically significant improvement in short‐term CSI scores. At long‐term follow‐up, patients with VFA had improvements that approached statistical significance with a mean baseline CSI of 22.56 decreasing to 14.56 (P = .057), while patients without VFA showed no improvement.

Conclusions

Our results are consistent with previous literature indicating efficacy of SLN block. The presence of VFA may be an indicator of patients who experience increased therapeutic effect.

Level of Evidence

4 Laryngoscope, 131:E2676–E2680, 2021
Net community metabolism of a Posidonia oceanica meadow
Authors: Champenois Willy , Borges Alberto V.
Published: April 2021

We report a 12‐yr data set (August 2006–October 2018) of nearly continuous estimates (n = 3275) of gross primary production (GPP), community respiration (CR), and net community production (NCP) in a Posidonia oceanica seagrass meadow, computed from O2 measurements on a mooring at 10 m bottom depth in the Bay of Revellata (Corsica). Both NCP and CR were correlated to GPP and followed the leaf biomass seasonal cycle. The meadow was net autotrophic (NCP of 23 ± 8 mol O2 m−2 yr−1, GPP [83 ± 16 mol O2 m−2 yr−1] > −CR [−60 ± 9 mol O2 m−2 yr−1]), in agreement with oxygen oversaturation (104% at annual scale, 101% in winter, and 109% in summer). Calcification (CAL) and CaCO3 dissolution (DIS) rates were evaluated from dissolved inorganic carbon measurements in benthic chamber incubations (August 2006–2009). The meadow was found to be a net sink of CaCO3 (DIS > CAL) at an annual rate of 7 mol CaCO3 m−2 yr−1 that matched estimates of CaCO3 deposition on the meadow by sedimentation from the water column. CAL from epiphyte coralline algae was correlated to GPP, but CAL : GPP ratio (0.1) was lower than reported for coralline algae in cultures (0.6) due to the additional contribution of Posidonia to GPP. Both NCP and net DIS contributed to an annual CO2 sink of −30 mol CO2 m−2 yr−1 distinctly stronger than the estimated net air‐sea CO2 flux (−1 mol CO2 m−2 yr−1). This suggests that CO2 input by vertical mixing and/or transport by horizontal advection also strongly contribute to the net atmospheric CO2 exchange.
Eutrophication alters bacterial co‐occurrence networks and increases the importance of chromophoric dissolved organic matter composition
Authors: Zhou Lei , Zhou Yongqiang , Tang Xiangming , Zhang Yunlin , Zhu Guangwei , Székely Anna J , Jeppesen Erik
Published: April 2021

Eutrophication affects bacterial communities by fueling them with nutrients and carbon sources. While the influence of physicochemical conditions on bacterial communities is well studied, little is known about how dissolved organic matter (DOM) quality affects bacterial interspecific interactions and community composition with increasing eutrophication. Here, we examined the relative importance of physicochemical conditions and chromophoric DOM (CDOM) composition for bacterial community variation across trophic gradients using 109 samples data collected in 33 lakes of the Yangtze‐Huaihe River basin. We found a notable increase of bacterial abundance, elevated modularity of co‐occurrence networks, and decreased habitat niche breadths from mesotrophic sites to hyper‐eutrophic sites, suggesting changes in co‐occurrence patterns with eutrophication. Variation partitioning revealed that the proportion purely explained by CDOM composition was higher at the moderate‐ and hyper‐eutrophic sites than at the mesotrophic sites. Moreover, the module structures of the networks correlated significantly with CDOM composition at the eutrophic sites but not at the mesotrophic sites. The significant negative correlation between community‐level habitat niche breadths and the intensities of the protein‐like components at the moderate‐ and hyper‐eutrophic sites indicates a strong association between biolabile protein‐like compounds and habitat specialists in nutrient and substrate enriched lake systems. Our results suggest that consideration of DOM composition can strengthen the identification of links between environmental factors and bacterial community composition and interspecific interactions, especially under resource‐rich conditions.
Warming exacerbates the impact of nutrient enrichment on microbial functional potentials important to the nutrient cycling in shallow lake mesocosms
Authors: Ren Lijuan , Liu Yuanyuan , Lauridsen Torben L. , Søndergaard Martin , Han Boping , Wang Jianjun , Jeppesen Erik , Zhou Jizhong , Wu Qinglong L.
Published: April 2021

Shallow lakes, the most numerous waterbodies on Earth, are susceptible to climate warming and nutrient enrichment whose effects on the microbial functional potentials are not yet fully understood, however. Here, we applied a microarray‐based technology termed GeoChip 5.0 to investigate microbial functional genes at the beginning of April in shallow lake ecosystems simulated in mesocosms that have been undergoing nutrient enrichment and warming for 9 yr. Our results showed that warming exacerbated the impact of nutrient enrichment on microbial metabolic potentials and significantly elevated the microbial autotrophy potentials, carbon degradation potentials (e.g., starch, hemicellulose, cellulose, and chitin), and polyphosphate mobilization potentials. We also observed that warming enhanced the impacts of nutrient enrichment on microbial functional gene structure. The combination of warming and nutrient enrichment increased the deterministic effect from phytoplankton, causing higher interlinking of microbial functional genes involved in the carbon, nitrogen, phosphorus, and sulfur cycling in correlation‐based networks. Overall, we propose that the joint effect of warming and nutrient enrichment promoted the autotrophic carbon supply and the heterotrophic carbon demand and changed the carbon fluxes in the experimental mesocosms.
Highly Ordered 3D Tissue Engineering Scaffolds as a Versatile Culture Platform for Nerve Cells Growth
Authors: Chen Tingkuo , Jiang Haiming , Zhu Yibin , Chen Xueliu , Zhang Dao , Li Xiang , Shen Fangcheng , Xia Hongyan , Min Yonggang , Xie Kang
Published: April 2021

Tissue engineering scaffolds provide an encouraging alternative for nerve injuries due to their biological support for nerve cell growth, which can be used for neuronal repair. Nerve cells have been reported to be mostly cultured on 2D scaffolds that cannot mimic the native extracellular matrix. Herein, highly ordered 3D scaffolds are fabricated for nerve cell culture by melt electrospinning writing, the microstructures and geometries of the scaffolds could be well modulated. An effective strategy for scaffold surface modification to promote nerve cell growth is proposed. The effects of scaffolds with different surface modifications, viz., plasma treatment, single poly‐D‐lysine (PDL) coating after plasma treatment, single laminin (LM) coating after plasma treatment, double PDL and LM coatings after plasma treatment, on PC12 cell growth are evaluated. Experiments show the scaffold modified with double PDL and LM coatings after plasma treatment facilitated the growth of PC12 cells most effectively, indicating the synergistic effect of PDL and LM on the growth of nerve cells. This is the first systematic and quantitative study of the effects of different scaffold surface modifications on nerve cell growth. The above results provide a versatile culture platform for growing nerve cells, and for recovery from peripheral nerve injury.
A two‐dimensional diffusion coefficient determination problem for the time‐fractional equation
Authors: Durdiev Durdimurod K. , Rahmonov Askar A. , Bozorov Zavqiddin R.
Published: April 2021

In this paper, we consider two‐dimensional inverse problem for a fractional diffusion equation. The inverse problem is reduced to the equivalent integral equation. For solving this equation, the contracted mapping principle is applied. The local existence and global uniqueness results are proven. Also, the stability estimate is obtained.
Technical Note: ID‐card‐size dosimeter based on radiochromic films for continuous personnel monitoring
Authors: Prikhodko Victor V. , Alexeyev Alexander S. , Guskov Pavel A. , Novikov Sergey G. , Somov Andrey I. , Svetukhin Vyacheslav V.
Published: April 2021

Purpose

This paper is aimed at investigating the feasibility of developing a personal dosimeter of cumulative radiation dose which would incorporate the following features: 1) a small size compared to that of a proximity ID card; 2) instant dose readout; 3) no power source; 4) moderate cost. The dosimeter is proposed as a potential replacement for TLD and OSL dosimeters used by nuclear industry workers and some medical staff groups.

Methods

An original detector design is developed containing a two‐color LED, two photodetectors located in one plane covered with a mirror coating. The power necessary for the operation comes from an RFID reader. A small (5x5 mm) piece of Gafchromic EBT3 photochromic film sensitive to both X‐ray and gamma radiation is used as a sensor. Irradiation of samples under X‐ray and gamma radiation is carried out in the dose range of 0.1 cGy–1 Gy. The transmittance spectra are measured in the 300 nm–1100 nm spectral range.

Results

Several prototypes of the dosimeter are presented, the distinctive features of which are the absence of the power source, easy transmitting of the dosimetric data via a RF channel, and a slim form factor. Several sources of dose uncertainties are analyzed and ways to eliminate them are outlined. The average dose confidence interval (α = 0.05) calculated from the response curve is shown to equal 0.02 cGy. This makes it possible to reliably measure doses as low as 0.1 cGy, which corresponds to the minimum value claimed for Gafchromic EBT3.

Conclusions

The proposed idea of an ID‐card‐size dosimeter is feasible and has a number of advantages over TLD and OSL dosimeters, in particular, instant reading of the dose data using RFID/NFC readers, and a possibility of integrating into ERP systems.
Low b‐value diffusion tensor imaging for measuring pseudorandom flow of cerebrospinal fluid
Authors: Bito Yoshitaka , Harada Kuniaki , Ochi Hisaaki , Kudo Kohsuke
Published: April 2021

Purpose

Cerebrospinal fluid (CSF) plays an important role in the clearance system of the brain. Recently, low b‐value diffusion tensor imaging (low‐b DTI) has been reported to be useful in the observation of CSF flow; however, the precise flow property observed by low‐b DTI has not been fully investigated. Accordingly, a mathematical framework of low‐b DTI is proposed for investigating CSF and clarifying its pseudorandom flow.

Theory

The framework will show that the limit of the diffusion tensor as b‐value decreases to zero approximately represents the covariance of the velocity distribution of the CSF’s pseudorandom flow.

Methods

The low b‐value diffusion tensor (DTL) of whole‐brain CSF was obtained using diffusion‐weighted echo‐planar imaging. Seven healthy volunteers were scanned for intersubject analysis; three of the volunteers was consecutively scanned for repeatability analysis. Obtained DTL was visually assessed by ellipsoid‐representation map and was statistically evaluated by calculating mean diffusivity (MD) and fractional anisotropy (FA) in regions of interest (ROIs) representing intensive pseudorandom flow.

Results

Obtained DTL consistently shows large and anisotropic diffusivity in some segments of CSF, typically the ROIs around the foramen of Monro, the aqueduct, the prepontine cistern, the middle cerebral artery, and the Sylvian fissure throughout the study. The statistical analysis shows high repeatability and consistently high MD and FA in all the ROIs for all the volunteers.

Conclusion

From the viewpoint of the proposed framework, the high and anisotropic DTL in the ROIs indicates large covariance of velocity distribution, which represents intensive pseudorandom flows of CSF.
Genetic Structure and Diversity of the Endemic Carolina Madtom and Conservation Implications
Authors: Cope W. Robert , Kwak Thomas J. , Black Tyler R. , Pacifici Krishna , Harris Sheila C. , Miller Caitlin M. , Raley Morgan E. , Hallerman Eric M.
Published: April 2021

Identification and conservation of genetic diversity within and among freshwater fish populations are important to better manage and conserve imperiled species. The Carolina Madtom Noturus furiosus is a small, nongame catfish that is endemic to the Tar and Neuse River basins of North Carolina. Genetic structure has not been studied in the species, and given recent population declines in both basins, identification of remaining genetic diversity within the species is vital for informing conservation efforts. To assess the status and trends of Carolina Madtom genetic structure, we analyzed genetic markers from 173 individuals to (1) define population genetic structure, (2) assess intra- and interbasin genetic differentiation in the Tar and Neuse River basins, and (3) present management implications to guide conservation efforts. Using 10 microsatellite primers developed for the related Yellowfin Madtom N. flavipinnis, we observed low genetic diversity in Carolina Madtoms. Genotype frequencies within samples were not in Hardy–Weinberg equilibrium, with a deficit of heterozygotes that could be due to family structure, inbreeding, or segregation of null alleles. Mean (±SD) M-ratios for the Tar River (0.414 ± 0.117) and Neuse River (0.117 ± 0.102) basin collections indicated that both populations have experienced recent demographic bottlenecks, with that in the Neuse River basin population being more severe. Effective population size estimates for the respective populations were small, on the order of tens of individuals, driving low genetic diversity within populations. However, the multilocus population differentiation metrics GST′ (mean ± SE = 0.135 ± 0.031) and DEST (0.125 ± 0.029) were significantly different from zero (P < 0.001), indicating significant genetic differentiation between the Tar and Neuse River basin populations. Our findings will inform managers on the status of genetic variation in the Carolina Madtom and will guide conservation toward protective listing and management decisions to maintain the viability of this important endemic species.
Community leadership as multi‐dimensional capacities: A conceptual framework and preliminary findings for community foundations
Authors: Wu Viviana Chiu Sik
Published: April 2021

Community foundations are increasingly looked to as community leaders that coalesce money, people, knowledge, and networks for addressing public problems at the local level. However, the field remains difficult to grasp—what it is and how it materializes in practice. Drawing from both academic and practitioner literature, this article proposes a multidimensional conceptual framework that construes community leadership in six capacities ranging from (a) strategizing, (b) convening, (c) knowledge building, (d) capacity building, (e) partnering, to (f) policy engagement. I applied this conceptual framework to analyze 539 annual reports of U.S. community foundations using semi‐automated content analysis. The empirical analysis shows that they tend to specialize in one or a few leadership capacities, but not necessarily all six components. In particular, the capability approach to community leadership through capacity building, partnering, and policy engagement is more favorable among community foundations than a participatory approach through convening and knowledge building. This article contributes to building the conceptual foundation and provides preliminary evidence to advance future research on the foundations' role in community leadership.
Safety and Feasibility of Radiotherapy Plus Camrelizumab for Locally Advanced Esophageal Squamous Cell Carcinoma
Authors: Zhang Wencheng , Yan Cihui , Gao Xuan , Li Xiaoxia , Cao Fuliang , Zhao Gang , Zhao Jingjing , Er Puchun , Zhang Tian , Chen Xi , Wang Yuwen , Jiang Yao , Wang Quanren , Zhang Baozhong , Qian Dong , Wang Jun , Zhou Dejun , Ren Xiubao , Yu Zhentao , Zhao Lujun , Yuan Zhiyong , Wang Ping , Pang Qingsong
Published: April 2021

Lessons Learned

Background

We conducted a phase Ib study of radiotherapy plus programmed cell death protein 1 (PD-1) monoclonal antibody camrelizumab as first-line treatment for locally advanced esophageal squamous cell carcinoma (ESCC).

Methods

We planned to enroll 20 patients with newly diagnosed locally advanced ESCC. Patients received 60 Gy radiation (2.0 Gy/fraction, 5 fractions/week), with camrelizumab (200 mg every 2 weeks) starting with radiotherapy and continuing for 32 weeks (i.e., for 16 cycles). The primary endpoints were safety and feasibility. Secondary endpoints were rates of radiologic and pathologic response, overall survival (OS), and progression-free survival (PFS). Study data were collected by the week during radiotherapy (RT), every month during the maintenance camrelizumab treatment, and every 3 months after treatment. Tumor microenvironment and peripheral blood were monitored at baseline and after 40 Gy radiation for association with efficacy.

Results

Twenty patients were enrolled and received treatment. One patient (patient 10) was excluded upon discovery of a second tumor in the bladder during treatment, leaving 19 patients for analysis. Toxicity was deemed tolerable. Fourteen (74%) patients had assessed objective response. At a median follow-up time of 31.0 months (95% confidence interval [CI], 27.0–35.1), median OS and PFS times were 16.7 months (95% CI, 5.9–27.9) and 11.7 months (95% CI, 0–30.3), respectively. OS and PFS rates at 24 months were 31.6% and 35.5%, respectively. Kaplan-Meier analysis revealed associations between the following factors and OS/PFS: tumor programmed cell death ligand 1 (PD-L1) expression, PD-1+CD8+, PD-1+CD4+ T cells, and PD-L1+CD4+ T cells; peripheral blood CD4+, CD8+, CD4+ regulatory T cells, and their subsets.

Conclusion

Radiotherapy plus camrelizumab had manageable toxicity and antitumor efficacy for locally advanced ESCC. Several biomarkers were associated with clinical benefit and deserve further study.
A PhaseIIStudy of Durvalumab in Combination with Tremelimumab in Patients with Rare Cancers
Authors: Edenfield William Jeffery , Chung Ki , O'Rourke Mark , Cull Elizabeth , Martin Julie , Bowers Heather , Smith Wesley , Gluck William Larry
Published: April 2021

Lessons Learned

Disease control with signals of response were demonstrated, which should lead to future validating clinical trials using checkpoint inhibitors in this underserved rare malignancy population. Although the study of single types of rare cancers is practically challenging, clinical trial designs that aggregate such patients into cohorts treated similarly are feasible, even in the community setting.

Background

Patients with rare cancers are an underserved population with limited access to clinical trials aside from phase I trials in the refractory setting. Treatment of these patients is often based on collections of anecdotes and small denominator review articles. Despite broad evidence of efficacy of combined immune checkpoint blockade across multiple tumor types, patients with rare tumors have not been afforded the opportunity for these therapies.

Methods

A phase II, investigator-initiated, single institution trial using durvalumab (1,500 mg every [Q]4 weeks × 13) and tremelimumab (75 mg Q4 weeks × 7, then Q12 weeks × 2) is reported. The population included 50 patients with advanced rare solid tumors (incidence <6/100,000 per year). The phase II dose and safety profile were defined in prior phase I trials. All patients had exhausted standard therapy options and all had received at least one prior line of systemic therapy (n = 49) unless a standard treatment option did not exist (n = 1).

Results

A complete response was demonstrated in one patient with anal cancer. Striking partial responses were seen in four patients. Prolonged disease stability was noted in 18 patients. Thirteen patients experienced disease progression. Patients were considered unevaluable if unable to initiate therapy (n = 6) or unable to complete two cycles of therapy (n = 8). In all cases, patients were unevaluable because of clinical deterioration. The toxicity profile paralleled prior published studies. Toxicities were manageable and without new signals. There were two events of grade 4 immune-mediated hepatitis and one death from pneumonitis.

Conclusion

This single-cohort basket trial demonstrated clinical activity from combined checkpoint blockade in 23 of the 36 evaluable patients. Patients with rare cancers, not eligible for immunotherapy via conventional clinical trial mechanisms, should be considered for this therapy through compassionate use, further clinical trials, and national registry programs.
Carbonized polymer dots with dual‐wavelength emission for labeling nucleoli in live cells through hydrogen bonding‐induced aggregation
Authors: Guan Linbo , He Ping , Chang Jinming , Yong Qiwen , Lei Jingxin , Wu Bo , Yuan Anqian , Xiao Yao , Bai Huai
Published: April 2021

We prepared carboxyl‐containing carbonized polymer dots (CPDs) with dual‐wavelength emission through a simple hydrothermal method. The CPDs emit blue light in live cells under the excitation at 405 nm, and show green fluorescence in cytoplasm and nucleoli when excited at 488 nm. No fluorescence can be seen in nuclei except nucleoli under the excitation at 488 nm, which means that the CPDs have excellent ability of labeling nucleoli in live cells with low background interference. This ability of the CPDs is derived from the aggregation induced by the hydrogen bonding between the carboxyl groups of the CPDs and the hydroxyl groups of ribonucleic acid at nucleoli. Fluorescence and cell culture passage experiments prove that the CPDs have no strong interaction with RNA, and all of them can be excreted out of cells in a couple of days. In vivo imaging for Caenorhabditis elegans indicates that the CPDs show the possibility of labeling nucleoli in live organisms in real‐time.
Synthesis and characterization of poly(L‐lactide)‐block‐poly(ε‐caprolactone)‐grafted titanium dioxide nanoparticles via ring‐opening in situ grafting polymerization
Authors: Ebrahimi Hossein , Sharif Farhad , Ramazani SA Ahmad
Published: April 2021

The synthesis of nanocomposites via in situ grafting polymerization due to its ability to produce polymeric materials with promising microscopic and macroscopic characteristics is becoming very attractive. In this paper, different poly(L‐Lactide)‐block‐poly(ε‐caprolactone) (PLLA‐b‐PCL) copolymers were in situ synthesized in the presence of modified titanium dioxide (TiO2) nanoparticles (mTNP) as the initiator and stannous octoate as the catalyst. The surface of TiO2 was modified by grafting aminopropyl trimethoxy silane to improve initiator efficiency. Copolymers with 90/10, 70/30, and 50/50 mass ratio of L‐lactide/ ε‐caprolactone and 5 wt% of mTNP (proportional to ε‐caprolactone) were synthesized. The samples were characterized by HNMR, CNMR, FTIR, GPC, TGA, TEM, and DSC, confirming the successful formation of PLLA‐b‐PCL on the surface of mTNP. Tensile test results showed the synthesized nanocomposite with mass ratio of LLA/CL = 70/30 had optimum mechanical properties among other nanocomposites and also in comparison with the neat PLA.