bluuebunny/crossref_metadata_2025 huggingface dataset:
Measles epidemiology and viral nucleoprotein gene evolution in Shandong Province, China
Authors: Yuan Chuang , Wang Cheng , Zhu Kongfu , Li Song , Miao Zengmin
Published: June 2022

Measles, caused by measles virus (MeV), has not been eradicated in many regions and countries, threatening human health. Thus, it is beneficial for measles elimination to understand measles epidemiology and molecular evolution of key viral genes, such as nucleoprotein (N) gene. Based on public data, measles epidemiological information and MeV N gene sequences reported in Shandong Province, China were comprehensively collected and systematically analyzed. The results showed a positive correlation between population density and measles incidence (r = +0.31), while negative correlations were found between measles incidence and healthcare condition (r = −0.21) as well as average routine vaccination rate (r = −0.11). Additionally, the predominant lineage of MeV in Shandong was formed by genotype H1 strains, and the time of the most recent common ancestor of the N gene of MeV genotype H1 in Shandong traced back to 1987 (95% highest posterior density, 1984–1990) with relatively rapid evolution (mean rate, 1.267 × 10−3 substitutions/site/year). The genetic diversity of MeV N gene increased with the substantial emergence of major divergent clades of genotype H1 before 2005 and then remained relatively high and stable. In summary, these findings provided a significant insight into the measles elimination.
Evaluation of diagnostic test procedures for SARS‐CoV‐2 using latent class models
Authors: Stærk‐Østergaard Jacob , Kirkeby Carsten , Christiansen Lasse E. , Andersen Michael A. , Møller Camilla H. , Voldstedlund Marianne , Denwood Matthew J.
Published: June 2022

Polymerase chain reaction (PCR) and antigen tests have been used extensively for screening during the severe acute respiratory syndrome coronavirus 2 pandemics. However, the real‐world sensitivity and specificity of the two testing procedures in the field have not yet been estimated without assuming that the PCR constitutes a gold standard test. We use latent class models to estimate the in situ performance of both tests using data from the Danish national registries. We find that the specificity of both tests is very high (>99.7%), while the sensitivities are 95.7% (95% confidence interval [CI]: 92.8%–98.4%) and 53.8% (95% CI: 49.8%–57.9%) for the PCR and antigen tests, respectively. These findings have implications for the use of confirmatory PCR tests following a positive antigen test result: we estimate that serial testing is counterproductive at higher prevalence levels.
Free and glycosylated aroma compounds in grapes monitored by solid‐liquid extraction and dispersive liquid‐liquid microextraction combined with gas chromatography‐mass spectrometry
Authors: Oller‐Ruiz Ainhoa , Viñas Pilar , Hernández‐Córdoba Manuel , Fenoll José , Garrido Isabel , Campillo Natalia
Published: June 2022

Fifteen aroma compounds have been determined in their free and glycosylated forms in grapes using dispersive liquid‐liquid microextraction with gas chromatography‐mass spectrometry. The sample treatment includes a previous solid‐liquid extraction stage and subsequent parallel microextraction approaches to preconcentrate total aroma content and the free fraction. Thus, the extraction of the total content of analytes requires previous enzymatic hydrolysis of the bound forms. For preconcentration, chloroform (250 μl) and acetonitrile (1.5 ml) were added to 10 ml of the sample extract in the presence of 0.5 g sodium chloride. The absence of matrix effect in the samples allowed quantification against aqueous external standards. Limits of detection ranged between 5 and 30 ng/g, depending on the compound. Method accuracy was studied through recovery assays, with recoveries in the 82–115% range being obtained. Relative standard deviations for repeatability studies were lower than 12%. Four different samples of grapes were analyzed, being quantified linalool in its free form at concentrations in the 359–470 ng/g range, and benzyl alcohol, 2‐phenylethanol, and linalool oxide I and II in their bound forms between 52 and 464 ng/g.
Knowledge sharing in organization: Reviewing the foundations of the field and current themes using bibliometrics
Authors: Anand Amitabh , Dumazert Jean‐Pierre
Published: June 2022

Understanding the history, evolution, and present tendencies of a discipline requires a thorough review of its literature. Despite various review studies on the field of knowledge management (KM), its subdiscipline ‘knowledge sharing’ has only seen a handful of investigations with a slew of limitations. As a result, the present work aims to conduct a review of existing literature on knowledge sharing (KS) using complementary bibliometric methodologies. To do this, we conduct our reviews using two complimentary bibliometric techniques: ‘Co‐citation Reference Analysis’ (CCA‐R) and ‘Bibliographic Coupling Document Analysis’ (BCA‐D), and we highlight the field's origins and current themes. We then map our findings using free science visualization software (VOS viewer). The study's implications are examined, and we show new paths for further research.
Dimensions of Network Polymers
Authors: Tobita Hidetaka
Published: June 2022

The mean‐square radius of gyration Rg2 and the graph diameter D of the network polymers formed through the random crosslinking of predetermined primary chains with a fixed number of intermolecular and intramolecular crosslinks are investigated by the numerical calculation based on the graph theory. In the case of ring‐free polymers, D is the longest end‐to‐end path length, sometimes referred to as the maximum span length. The expected Rg2‐value for a given D is found to follow a linear relationship, Rg2 = a D + b, similarly as in the cases of the ring‐free polymers. The proportional coefficient, a decreases approximately linearly with the number of intramolecular crosslinks kc, or the cycle rank in the graph theory, essentially independent of the total number k of crosslinks and the primary chain length distribution. The contraction factor g of the average Rg2 of the whole network polymer system is also governed by kc, and decreases with kc. One may be able to design and control the Rg2‐values of crosslinked polymers through the magnitude of D, which is usually easier to imagine than the complex 3D architecture.
Whole‐genome circulating tumor DNA methylation landscape reveals sensitive biomarkers of breast cancer
Authors: Hai Luo , Li Lingyu , Liu Zongzhi , Tong Zhongsheng , Sun Yingli
Published: June 2022

The changes in circulating tumor DNA (ctDNA) methylation are believed to be early events in breast cancer initiation, which makes them suitable as promising biomarkers for early diagnosis. However, applying ctDNA in breast cancer early diagnosis remains highly challenging due to the contamination of background DNA from blood and low DNA methylation signals. Here, we report an improved way to extract ctDNA, reduce background contamination, and build a whole‐genome bisulfite sequencing (WGBS) library from different stages of breast cancer. We first compared the DNA methylation data of 74 breast cancer patients with those of seven normal controls to screen candidate methylation CpG site biomarkers for breast cancer diagnosis. The obtained 26 candidate ctDNA methylation biomarkers produced high accuracy in breast cancer patients (area under the curve [AUC] = 0.889; sensitivity: 100%; specificity: 75%). Furthermore, we revealed potential ctDNA methylated CpG sites for detecting early‐stage breast cancer (AUC = 0.783; sensitivity: 93.44%; specificity: 50%). In addition, different subtypes of breast cancer could be well distinguished by the ctDNA methylome, which was obtained through our improved ctDNA‐WGBS method. Overall, we identified high specificity and sensitivity breast cancer‐specific methylation CpG site biomarkers, and they will be expected to have the potential to be translated to clinical practice.
Common institutional ownership and corporate misconduct
Authors: Wang Ziwei , Wang Chunfeng , Fang Zhenming
Published: June 2022

This paper explores the relationship between common institutional ownership and corporate misconduct. Empirical evidence indicates that common institutional blockholders (institutional blockholders with multiple blockholdings), with advantages in information, experience and resources, can effectively inhibit corporate misconduct. Furthermore, the inhibitory effect is stronger in firms prone to commit misconduct. Empirical results also support the role of state blockholders with multiple blockholdings and common institutional blockholders with high ownership proportions in restraining corporate misconduct. This paper contributes to the heated debate on the economic implications of common ownership and provides additional evidence for the role of common blockholders in Chinese capital markets.
Solvability of the boundary‐value problem for a mixed equation involving hyper‐Bessel fractional differential operator and bi‐ordinal Hilfer fractional derivative
Authors: Karimov Erkinjon , Ruzhansky Michael , Toshtemirov Bakhodirjon
Published: June 2022

In a rectangular domain, a boundary‐value problem is considered for a mixed equation with a regularized Caputo‐like counterpart of hyper‐Bessel differential operator and the bi‐ordinal Hilfer's fractional derivative. By using the method of separation of variables a unique solvability of the considered problem has been established. Moreover, we have found the explicit solution of initial‐boundary problems for the heat equation with the regularized Caputo‐like counterpart of the hyper‐Bessel differential operator with the non‐zero starting point.
Solid‐state 31P and 109Ag CP/MAS NMR as a powerful tool for studying of silver(I) complexes with N‐thiophosphorylated thiourea and thioamide ligands
Authors: Rakhmatullin Aydar , Brusko Vasiliy V. , Shcherbitskaya Elmira R. , Polovov Ilya B. , Bakirov Rinat , Bessada Catherine
Published: June 2022

A family of three‐ and four‐coordinated silver(I) complexes of formulas [Ag(PPh3)2L], [Ag(PPh3)L], and [AgL]n with N‐thiophosphorylated thiourea and thioamide ligands of general formula RC(S)NHP(S)(OPri)2 [R = Ph, PhNH, iPrNH, tBuNH, NH2] have been studied by solid‐state 109Ag and 31P CPMAS NMR spectroscopy. 109Ag NMR spectra have provided valuable structural information about Ag coordination, which is in good accordance with the available crystal structure data. The data presented in this work represent a significant addition to the available 109Ag chemical shifts and chemical shifts anisotropies. The silver chemical shift ranges for different P,S‐environments and coordination state were discussed in detail. The 1J(31P–107/109Ag) and 2J(31P–31P) values were determined and analyzed.
Free‐breathing motion‐informed locally low‐rank quantitative 3D myocardial perfusion imaging
Authors: Hoh Tobias , Vishnevskiy Valery , Polacin Malgorzata , Manka Robert , Fuetterer Maximilian , Kozerke Sebastian
Published: June 2022

Purpose

To propose respiratory motion‐informed locally low‐rank reconstruction (MI‐LLR) for robust free‐breathing single‐bolus quantitative 3D myocardial perfusion CMR imaging. Simulation and in‐vivo results are compared to locally low‐rank (LLR) and compressed sensing reconstructions (CS) for reference.

Methods

Data were acquired using a 3D Cartesian pseudo‐spiral in‐out k‐t undersampling scheme (R = 10) and reconstructed using MI‐LLR, which encompasses two stages. In the first stage, approximate displacement fields are derived from an initial LLR reconstruction to feed a motion‐compensated reference system to a second reconstruction stage, which reduces the rank of the inverse problem. For comparison, data were also reconstructed with LLR and frame‐by‐frame CS using wavelets as sparsifying transform (‐wavelet).

Reconstruction accuracy relative to ground truth was assessed using synthetic data for realistic ranges of breathing motion, heart rates, and SNRs. In‐vivo experiments were conducted in healthy subjects at rest and during adenosine stress. Myocardial blood flow (MBF) maps were derived using a Fermi model.

Results

Improved uniformity of MBF maps with reduced local variations was achieved with MI‐LLR. For rest and stress, intra‐volunteer variation of absolute and relative MBF was lower in MI‐LLR (±0.17 mL/g/min [26%] and ±1.07 mL/g/min [33%]) versus LLR (±0.19 mL/g/min [28%] and ±1.22 mL/g/min [36%]) and versus ‐wavelet (±1.17 mL/g/min [113%] and ±6.87 mL/g/min [115%]). At rest, intra‐subject MBF variation was reduced significantly with MI‐LLR.

Conclusion

The combination of pseudo‐spiral Cartesian undersampling and dual‐stage MI‐LLR reconstruction improves free‐breathing quantitative 3D myocardial perfusion CMR imaging under rest and stress condition.
Free‐breathing, non‐ECG, simultaneous myocardial T1, T2, T2*, and fat‐fraction mapping with motion‐resolved cardiovascular MR multitasking
Authors: Cao Tianle , Wang Nan , Kwan Alan C. , Lee Hsu‐Lei , Mao Xianglun , Xie Yibin , Nguyen Kim‐Lien , Colbert Caroline M. , Han Fei , Han Pei , Han Hui , Christodoulou Anthony G. , Li Debiao
Published: June 2022

Purpose

To develop a free‐breathing, non‐electrocardiogram technique for simultaneous myocardial T1, T2, T2*, and fat‐fraction (FF) mapping in a single scan.

Methods

The MR Multitasking framework is adapted to quantify T1, T2, T2*, and FF simultaneously. A variable TR scheme is developed to preserve temporal resolution and imaging efficiency. The underlying high‐dimensional image is modeled as a low‐rank tensor, which allows accelerated acquisition and efficient reconstruction. The accuracy and/or repeatability of the technique were evaluated on static and motion phantoms, 12 healthy volunteers, and 3 patients by comparing to the reference techniques.

Results

In static and motion phantoms, T1/T2/T2*/FF measurements showed substantial consistency (R > 0.98) and excellent agreement (intraclass correlation coefficient > 0.93) with reference measurements. In human subjects, the proposed technique yielded repeatable T1, T2, T2*, and FF measurements that agreed with those from references.

Conclusions

The proposed free‐breathing, non‐electrocardiogram, motion‐resolved Multitasking technique allows simultaneous quantification of myocardial T1, T2, T2*, and FF in a single 2.5‐min scan.
Delayed pregnancy detection and return to fertility with extended levonorgestrel‐containing oral contraceptives: A real world setting cohort study
Authors: Kaplan Sigal , Bertoia Monica L. , Lass Amir , Wang Florence T. , Evans Alison , Dhanda Sandeep , Roy Debabrata , Seeger John D.
Published: June 2022

Purpose

As part of the European risk management plan of a 91‐day extended levonorgestrel‐containing combined oral contraceptive (COCLNG), a study was performed to assess its safety. This analysis was conducted to examine delayed pregnancy detection and return to fertility with extended combined oral contraceptives (COC).

Methods

We conducted a retrospective cohort study in new users of 91‐day COCLNG or 28‐day COCLNG within a US‐based healthcare claims database from 2006 to 2017. Delayed pregnancy detection during current COCLNG exposure was defined as the time between estimated pregnancy start and first prenatal care encounter. Additionally, the time between estimated pregnancy start and COCLNG discontinuation was measured. To measure return to fertility, pregnancy rates were estimated among females who discontinued treatment. 91‐day COCLNG users were propensity score‐matched to 28‐day COCLNG users. Hazard ratio for pregnancy was calculated using Cox proportional hazards models.

Results

The 91‐day and 28‐day COCLNG users had 25 593 and 76 586 treatment episodes, respectively. The median time to pregnancy detection was 64.5 and 61.0 days (p = 0.24) in users of 91‐day COCLNG and 28‐day COCLNG. The median exposure time to treatment after estimated pregnancy start was 54.0 and 38.0 days (p < 0.01). In the fertility analysis, pregnancy rates were 54.82 (95% CI, 50.05–59.93) and 69.30 (95% CI, 64.98–73.82) per 1000 person‐years in extended COCLNG discontinuers and 28‐day COCLNG discontinuers. The adjusted hazard ratio of pregnancy was 0.77 (95% CI, 0.69–0.85).

Conclusions

Small differences were observed for pregnancy rates and delayed pregnancy detection between 91‐day extended COCLNG and 28‐day COCLNG, which may be related to the longer days' supply of extended COCLNG. Differences in the fertility analysis may be related to unmeasured residual confounding.
Recyclable photoluminescent composites via incorporating ZnS‐based phosphors into dynamic crosslinking elastomeric matrixes
Authors: Wang Jinyun , Xia Biao , Su Tong , Lin Tengfei , Gao Min , Zhao Chunlin , Wu Xiao , Lin Cong
Published: June 2022

The rapid advances in photochromic devices have spurred great enthusiasm in the design and preparation of luminescent materials. It is an efficient and facile strategy to incorporate ZnS‐based phosphors into crosslinking polymer substrates, obtaining photochromic materials with excellent comprehensive properties. However, crosslinking polymeric ZnS‐based phosphor luminous materials are unable to be recycled and reprocess at the end of service, limiting their long‐term utilization and burdening the environment. Besides, few reported works have explored photoluminescent properties of samples during multiple reprocessing and recycling. Herein, enlightened by the intriguing dynamic covalent crosslinking technology, recyclable and photoluminescent elastomers, employed polymeric flexible matrixes with dynamic covalent joints integrated with ZnS:Cu and ZnS:Cu,Mn phosphors, were prepared in this work. Due to the breakage and reformation of exchangeable crosslinking connections and intensive interfacial interactions between polar elastomeric matrixes and luminophores, the original and recycled composites exhibit excellent recyclable, photoluminescent, and mechanical properties. We anticipate that the strategy of this work, inserted phosphors into dynamic crosslinking polymer matrixes with a facile fabrication process, paves the way for the recycling and long‐term utilization of photoluminescent materials.
Optimal analytical strategies for sensitive and quantitative phosphoproteomics using TMT‐based multiplexing
Authors: Koenig Claire , Martinez‐Val Ana , Franciosa Giulia , Olsen Jesper V.
Published: June 2022

In large‐scale quantitative mass spectrometry (MS)‐based phosphoproteomics, isobaric labeling with tandem mass tags (TMTs) coupled with offline high‐pH reversed‐phase peptide chromatographic fractionation maximizes depth of coverage. To investigate to what extent limited sample amounts affect sensitivity and dynamic range of the analysis due to sample losses, we benchmarked TMT‐based fractionation strategies against single‐shot label‐free quantification with spectral library‐free data independent acquisition (LFQ‐DIA), for different peptide input per sample. To systematically examine how peptide input amounts influence TMT‐fractionation approaches in a phosphoproteomics workflow, we compared two different high‐pH reversed‐phase fractionation strategies, microflow (MF) and stage‐tip fractionation (STF), while scaling the peptide input amount down from 12.5 to 1 μg per sample. Our results indicate that, for input amounts higher than 5 μg per sample, TMT labeling, followed by microflow fractionation (MF) and phospho‐enrichment, achieves the deepest phosphoproteome coverage, even compared to single shot direct‐DIA analysis. Conversely, STF of enriched phosphopeptides (STF) is optimal for lower amounts, below 5 μg/peptide per sample. As a result, we provide a decision tree to help phosphoproteomics users to choose the best workflow as a function of sample amount.
Green and rapid fabrication of copper oxide in enhanced electrode liquid phase plasma system
Authors: Yang Jason H. C. , Wu Shang‐Lin , Tsai Cheng‐Shiun
Published: June 2022

Copper(II) oxide nanoparticles have been successfully fabricated in a rapid fashion by a green method which requires nothing more than ultrapure water and copper pallets. In this study, liquid phase plasma system has been deployed to facilitate the synthesis process with tunable parameters of duty cycle (θ), pulse period (τ), copper pallet length, and the distance between electrodes, which essentially contributes to increased particle collision, extended reaction period, enlarged reactant size, and widened space, respectively. X‐ray diffraction (XRD) profile shows at 2 theta = 35.6° and 38.7°, along with Fourier‐transform infrared spectroscopy (FT‐IR) characteristic peaks at 435, 528, and 598 cm−1 confirm the presence of highly pure CuO nanoparticles with crystallites about 55–70 nm in length and 15–26 nm in width that develop agglomerated nanoparticles ranging 155–160 nm in size. Results also reveal that serrated structure electrodes can improve the particle formation rate by 32% from 0.22 to 0.29 g/h.
Defining and identifying early‐onset lung disease in cystic fibrosis with cumulative clinical characteristics
Authors: Huang Leslie , Lai HuiChuan J. , Antos Nicholas , Rock Michael J. , Asfour Fadi , Howenstine Michelle , Gaffin Jonathan M. , Farrell Philip M.
Published: June 2022

Background

Because of the heterogeneity in cystic fibrosis (CF) lung disease among young children, a clinical method to identify early‐onset lung disease is needed.

Objective

To develop a CF early‐onset lung disease (CFELD) scoring system by utilizing prospectively collected longitudinal data on manifestations in the first 3 years of life.

Design

We studied 145 infants born during 2012–2017, diagnosed through newborn screening by age 3 months, and followed to 36 months of age. Cough severity, pulmonary exacerbations (PEx), respiratory cultures, and hospitalizations were collected at each CF center visit (every 1–2 months in infancy and quarterly thereafter). These data were used to construct the CFELD system and to classify lung disease into five categories: asymptomatic, minimal, mild, moderate, and severe.

Results

The most frequent manifestation of CF early lung disease was MD‐reported PEx episodes, PEx hospitalizations, and positive Pseudomonas aeruginosa cultures. Parent‐reported cough severity was correlated with the number of respiratory hospitalizations (r = 0.48, p < 0.0001). The distribution of CFELD categories was 10% asymptomatic, 17% minimal, 29% mild, 33% moderate, and 12% severe. The moderate and severe categories occurred threefold higher in pancreatic insufficient (PI, 49%) versus sufficient subjects (16%), p < 0.0001. In addition to PI, gastrointestinal and nutrition‐related hospitalizations, plasma cytokines interleukin (IL)‐6 and IL‐10, duration of CFTR modulator therapy, and type of health insurance were significant predictors of CFELD scores.

Conclusion

The CFELD scoring system is novel, allows systematic evaluation of lung disease prognosis early, and may aid in therapeutic decision‐making particularly in the initiation of CFTR modulator therapy.
Understanding patterns of internal migration during the COVID‐19 pandemic in Spain
Authors: González‐Leonardo Miguel , López‐Gay Antonio , Newsham Niall , Recaño Joaquín , Rowe Francisco
Published: June 2022

Existing empirical work has analysed the impacts of COVID‐19 on mortality, fertility and international migration. Less is known about the ways in which the COVID‐19 pandemic has influenced the patterns of internal migration. Anecdotal reports of mass migration from large cities to less populated areas have emerged, but lack of data has prevented empirically assessing this hypothesis. Drawing on geographically granular administrative population register data, we aim to analyse the extent of change in the patterns of internal migration across the urban hierarchy in Spain during 2020. Our results show a decline of 2.5% in the number of internal migration moves, particularly during the early stages of the pandemic, returning to pre‐pandemic levels in late 2020. Results also reveal unusually large net migration losses in core cities and net migration gains in rural areas. Net migration losses in cities and gains in rural areas particularly accumulated following the elimination of the strict lockdown measures in June. Yet, these net losses and gains trended to pre‐pandemic levels in late 2020, and movements between cities, and between cities and suburbs, continued to dominate the internal migration system. Thus, while the COVID‐19 pandemic exerted notable changes in the geographic balance of internal migration flows, these changes appear to have been temporary and did not significantly alter the existing structures of the national migration system.
Rainbow trees in uniformly edge‐colored graphs
Authors: Aigner‐Horev Elad , Hefetz Dan , Lahiri Abhiruk
Published: June 2022

We obtain sufficient conditions for the emergence of spanning and almost‐spanning bounded‐degree rainbow trees in various host graphs, having their edges colored independently and uniformly at random, using a predetermined palette. Our first result asserts that a uniform coloring of , using a palette of size , a.a.s. admits a rainbow copy of any given bounded‐degree tree on at most vertices, where is arbitrarily small yet fixed. This serves as a rainbow variant of a classical result by Alon et al. pertaining to the embedding of bounded‐degree almost‐spanning prescribed trees in , where is independent of . Given an ‐vertex graph with minimum degree at least , where is fixed, we use our aforementioned result in order to prove that a uniform coloring of the randomly perturbed graph , using colors, where is arbitrarily small yet fixed, a.a.s. admits a rainbow copy of any given bounded‐degree spanning tree. This can be viewed as a rainbow variant of a result by Krivelevich et al. who proved that , where is independent of , a.a.s. admits a copy of any given bounded‐degree spanning tree. Finally, and with as above, we prove that a uniform coloring of using colors a.a.s. admits a rainbow spanning tree. Put another way, the trivial lower bound on the size of the palette required for supporting a rainbow spanning tree is also sufficient, essentially as soon as the random perturbation a.a.s. has edges.
A Hemicyanine‐Assembled Upconversion Nanosystem for NIR‐Excited Visualization of Carbon Monoxide Bio‐Signaling In Vivo
Authors: Ye Minan , Zhang Jie , Jiang Detao , Tan Qi , Li Jingyun , Yao Cheng , Zhu Chenjie , Zhou Yi
Published: June 2022

Carbon monoxide (CO) is considered as the second gasotransmitter involved in a series of physiological and pathological processes. Although a number of organic fluorescent probes have been developed for imaging CO, these probes display excitation within the ultraviolet or visible range, which restrict their applications in the complex biosystems. In the present work, a strategy is developed to construct an upconversion nanoparticles‐based nanosystem for upconversion luminescent (UCL) sensing CO. This nanosystem exhibits a fast response to CO with high sensitivity and selectivity in aqueous solution by a near‐infrared‐excited ratiometric UCL detection method. Meanwhile, laser scanning upconversion luminescence microscope experiments demonstrate that this nanosystem can visualize the endogenous CO bio‐signaling in living cells, deep tissues, zebrafish, and living mice by ratiometric UCL imaging. In particular, this nanosystem has been successfully employed in visualization of the endogenous CO bio‐signaling through up‐regulation of heme oxygenase‐1 (HO‐1) in the progression of hypoxia, acute inflammation, or ischemic injury. This work demonstrates that the outstanding performance of the nanosystem not only can provide an effective tool for further understanding the role of CO in the physiological and pathological environment, but also may have great potential ability for tracking the expression of HO‐1 in living systems.
Construction of Core‐Shell NanoMOFs@microgel for Aqueous Lubrication and Thermal‐Responsive Drug Release
Authors: Wu Wei , Liu Jianxi , Gong Peiwei , Li Zhihuan , Ke Cheng , Qian Yong , Luo Haowen , Xiao Lishuang , Zhou Feng , Liu Weimin
Published: June 2022

The construction of porous nanocarriers with good lubricating performance and stimuli‐responsive drug release is significant for the synergetic therapy of osteoarthritis (OA). Although metal‐organic framework nanoparticles (nanoMOFs) as carriers can support drug delivery, achieving the synergy of aqueous lubrication and stimuli‐responsive drug release is challenging. In this work, a core‐shell nanoMOFs@poly(N‐isopropylacrylamide) (PNIPAm) microgel hybrid via one‐pot soap‐free emulsion polymerization is developed. Programmable growth of the PNIPAm microgel layer on the surface of nanoMOFs is achieved by tuning the concentration of the monomer and the crosslinker in the reaction. Reversible swelling‐collapsing behaviors of the hybrid are realized by tuning the temperature below and above the lower critical solution temperature. When used as water lubrication additives, the hybrid enables reductions in both the coefficient of friction and wear volume. In vitro thermal‐responsive drug release is demonstrated on the diclofenac sodium‐loaded hybrid by controlling the swelling and collapsing states of the PNIPAm nanolayer. Moreover, the good biocompatibility of the hybrid is verified by culturing toward HeLa and BEAS‐2B cells. These results establish a nanoMOFs@microgel hybrid that can achieve friction and wear reduction and thermal‐responsive drug release.
Increasing the level of resistant starch in ‘Presidio’ rice through multiplex CRISPR–Cas9 gene editing of starch branching enzyme genes
Authors: Biswas Sudip , Ibarra Oneida , Shaphek Mariam , Molina‐Risco Marco , Faion‐Molina Mayra , Bellinatti‐Della Gracia Marcela , Thomson Michael J. , Septiningsih Endang M.
Published: June 2022

Rice (Oryza sativa L.) is an excellent source of starch, which is composed of amylopectin and amylose. Resistant starch (RS) is a starch product that is not easily digestible and absorbed in the stomach or small intestine and instead is passed on directly to the large intestine. Cereals high in RS may be beneficial to improve human health and reduce the risk of diet‐related chronic diseases. It has been reported through chemical mutagenesis and RNA interference studies that starch branching enzymes (SBEs) play a major role in contributing to higher levels of RS in cereal crops. In this study, we used multiplex clustered regularly interspaced short palindromic repeat (CRISPR)–CRISPR associated protein 9 (Cas9) genome editing to simultaneously target all four SBE genes in rice using the endogenous transfer RNA (tRNA)‐processing system for expressing the single‐guide RNAs (sgRNAs) targeting these genes. The CRISPR–Cas9 vector construct with four SBE gene sgRNAs was transformed into the U.S. rice cultivar Presidio using Agrobacterium‐mediated transformation. Knockout mutations were identified at all four SBE genes across eight transgene‐positive T0 plants. Transgene‐free T1 lines with different combinations of disrupted SBE genes were identified, with several SBE‐edited lines showing significantly increased RS content up to 15% higher than the wild‐type (WT) cultivar Presidio. Although further efforts are needed to fix all of the mutant alleles as homozygous, our study demonstrated the potential of multiplex genome editing to develop high‐RS lines.
Examination of care processes and treatment optimization for head and neck cancer patients in a community setting “hub and hub” model
Authors: Sethi Harleen K. , Walker Elijah , Weinsheim Travis , Brennan Matthew J. , Fundakowski Christopher E.
Published: June 2022

Objective

To examine referral pattern, the timing of diagnostic/staging processes, and treatment initiation for new head and neck cancer patients in a community setting.

Methods

Patients with a newly diagnosed previously untreated diagnosis of head neck cancer managed at Asplundh Cancer Pavilion/Abington Memorial Hospital from October 2018 to March 2020. Source of referral and preceding workup were examined as well as intervals between initial head and neck consult and various timepoints of treatment initiation.

Results

One hundred and five patients were included in the study. The primary referral sources were external general otolaryngology (56.3%). Oral surgery and dermatology obtained tissue biopsy approximately 80% of the time before referral. The average time from the ordering of initial staging positron emission tomography/computed tomography to finalized results was 14 days (range: 10–25 days). Patients referred from dermatology and oral surgery were more likely to require single modality care, namely definitive surgical management. Time to treatment initiation average was 37 days (range: 29–41 days). Patients with longer treatment times noted significantly higher times to both radiation and medical oncology consults (48.42 vs. 18.13 days; P < 0.001).

Conclusions

No notable differences in treatment initiation times were identified based on referral source or extent of workup performed before head/neck surgery consult. It appears the largest opportunities for improvement in terms of reducing overall treatment length exist in the optimization of radiation initiation time.
Predictive value of pituitary tumor morphology on outcomes and complications in endoscopic transsphenoidal surgery
Authors: Heffernan Andrew T. , Han Joseph K. , Campbell John , Reese James , Day William G. , Edwards Joshua , Singh Ran V. , Zhu Wylie , Lam Kent K.
Published: June 2022

Purpose

Endoscopic transsphenoidal surgery (ETSS) is an increasingly utilized approach for resection of pituitary tumors. Prior studies have evaluated preoperative tumor size, location, and extent as prognostic factors for surgical resection. There is little data on the relationship between preoperative pituitary tumor radiographic morphology and surgical outcomes.

Study Design

Retrospective longitudinal study.

Setting

Single tertiary care institution.

Subjects and Methods

Preoperative magnetic resonance imaging and computed tomography scans from patients undergoing ETSS for pituitary tumor resections from 2007 to 2017 were retrospectively evaluated. A neuroradiologist classified these pituitary tumors into six morphologic groups, each defined by volume, dimensions, extension, and shape. Surgical difficulty, rates of incomplete resection, and postoperative complications were then stratified in relation to the morphologic groups.

Results

Pituitary tumors from 131 patients were classified from preoperative imaging into six characteristic morphologies: (1) microtumor, (2) round, (3) transverse oblong, (4) superior‐inferior oblong, (5) bilobed, and (6) large lobulated. Tumors that were characterized with the large lobulated, bilobed, and transverse oblong morphologies correlated with higher rates of postoperative evidence of residual tumor (70%, 36%, and 47%, respectively, all P < 0.002). Likewise, large lobulated, bilobed, and transverse oblong morphologies were also associated with intraoperative cerebrospinal fluid leaks (70%, 31%, and 35%, respectively, all P < 0.05).

Conclusions

We describe a novel descriptive system for the morphology of pituitary tumors that can be determined from preoperative imaging. Different tumor morphologic groups are associated with varying degrees of gross tumor resection, complications, and surgical difficulty. Utilizing pituitary tumor morphology may aid surgeons in planning the extent of resection, need for complex closure, and patient counseling.
Implementation of an enhanced recovery after surgery protocol for head and neck cancer patients: Considerations and best practices
Authors: Prasad Aman , Chorath Kevin , Barrette Louis‐Xavier , Go Beatrice , Deng Jie , Moreira Alvaro , Rajasekaran Karthik
Published: June 2022

Enhanced recovery after surgery (ERAS) protocols have been developed in numerous surgical specialties as a means of systematically improving patient recovery, functional outcomes, cost savings, and resource utilization. Such multidisciplinary initiatives seek to minimize variability in several aspects of perioperative patient care, helping to reduce inpatient length of hospital stay, complications, and the overall resource and financial burden of surgical care. Head and neck oncology patients stand to benefit from the implementation of comprehensive ERAS protocols, as these patients have complex medical needs that may dramatically impact multiple aspects of their recovery, including breathing, eating, nutrition, pain, speech, swallowing, and communication. Implementing ERAS protocols for head and neck cancer patients may present unique challenges, and require significant interdisciplinary coordination and collaboration. We therefore sought to provide a comprehensive guide to the planning and institution of such ERAS systems at institutions undertaking care of head and neck cancer patients. Key elements to consider in the implementation of successful ERAS protocols for this population include organizing a team consisting of frontline leaders such as nursing staff, medical specialists, and associated health professionals; designing interventions based on systematically evaluated, high‐quality literature; and instituting a clear methodology for regularly updating protocols and auditing the success or potential limitations of a given intervention. Potential obstacles to the success of ERAS interventions for head and neck cancer patients include challenges in systematically tracking progress of the protocol, as well as resource limitations in a given health system.
Burnout and well‐being in otolaryngology trainees: A systematic review
Authors: Lawlor Skye K. , Low Christopher M. , Carlson Matthew L. , Rajasekaran Karthik , Choby Garret
Published: June 2022

Objective

To comprehensively review the recent published literature to characterize current trends of burnout and well‐being among otolaryngology trainees.

Methods

Study design: systematic review and meta‐analysis. A comprehensive literature review from 2000 to 2021 of studies related to otolaryngology resident burnout and well‐being, as well as the general topic of well‐being among surgical residents was completed. All included studies were summarized qualitatively. For the quantitative analysis, only articles reporting a Maslach burnout inventory (MBI), modified MBI or Mini‐Z‐ Burnout assessment were included.

Results

Twenty‐five articles were included in the qualitative summary and nine articles in the quantitative analysis. In the qualitative summary, trainees were reported to have increased levels of distress and emotional hardening compared to attending otolaryngologists. Total hours worked per week and female gender were associated with worsened well‐being. Residency program strategies to improve trainee well‐being include program‐sponsored wellness activities, dedicated wellness champions, and assistance with clerical burden. Implementation of protected nonclinical time has been shown to decrease burnout and increase well‐being among trainees. Moreover, formal trainee mentorship programs have also been shown to reduce trainee burnout and stress. In the quantitative analysis, rates of trainee burnout ranged from 29.7% to 86% with an overall trend towards reduced rates of burnout from 2006 to 2021. Utilizing a weighted average, the overall burnout among otolaryngology residents was 58.6%.

Conclusions

Rates of burnout remain high among otolaryngology trainees. Implementing formal mentorship programs and providing protected time during regular work hours appear to be effective tools to improve resident well‐being.
Is the clinical head impulse test helpful in cochlear implantation candidacy evaluation?
Authors: Jiam Nicole T. , Cai Yi , Wai Katherine C. , Polite Colleen , Kramer Kurt , Sharon Jeffrey D.
Published: June 2022

Objective

Vestibular dysfunction is a known risk of cochlear implantation (CI). However, the utility of the physical exam to screen CI candidates for vestibular dysfunction is not well‐studied. The objective of this study is to evaluate the preoperative role of the clinical head impulse test (cHIT) in subjects undergoing CI surgery evaluation.

Study Design Setting, and Subjects

We conducted a retrospective review of 64 adult CI candidacy cases between 2017 and 2020 at a tertiary health care center.

Methods

All patients underwent audiometric testing and evaluation by the senior author. Patients with an abnormal catch‐up saccade contralateral to their worse hearing ear during cHIT were referred for formal vestibular testing. Outcomes included clinical and formal vestibular results, operated ear with regard to audiometric and vestibular results, and postoperative vertigo.

Results

Among all CI candidates, 44% (n = 28) reported preoperative disequilibrium symptoms. Overall, 62% (n = 40) of the cHITs were normal, 33% (n = 21) were abnormal, and 5% (n = 3) were inconclusive. There was one patient who presented with a false positive cHIT. Among the patients who endorsed disequilibrium, 43% had a positive preoperative cHIT. Fourteen percent of the subjects (n = 9) without disequilibrium had an abnormal cHIT. In this cohort, bilateral vestibular impairment (71%) was more common than unilateral vestibular impairment (29%). In 3% of the cases (n = 2), surgical management was revisited or altered due to cHIT findings.

Conclusion

There is a high prevalence of vestibular hypofunction in the CI candidate population. Self‐reported assessments of vestibular function are often not congruent with cHIT results. Clinicians should consider incorporating cHITs as part of the preoperative physical exam to potentially avoid bilateral vestibular dysfunction in a minority of patients.
Enhanced recovery after surgery protocols for outpatient operations in otolaryngology: Review of literature
Authors: Chorath Kevin , Hobday Sara , Suresh Neeraj V. , Go Beatrice , Moreira Alvaro , Rajasekaran Karthik
Published: June 2022

Objective

Enhanced recovery after surgery (ERAS) protocols are patient‐centered, evidence‐based pathways designed to reduce complications, promote recovery, and improve outcomes following surgery. These protocols have been successfully applied for the management of head and neck cancer, but relatively few studies have investigated the applicability of these pathways for other outpatient procedures in otolaryngology. Our goal was to perform a systematic review of available evidence reporting the utility of ERAS protocols for the management of patients undergoing outpatient otolaryngology operations.

Methods

A systematic literature review was conducted using MEDLINE, EMBASE, SCOPUS, and gray literature. We identified studies that evaluated ERAS protocols among patients undergoing otologic, laryngeal, nasal/sinus, pediatric, and general otolaryngology operations. We assessed the outcomes and ERAS components across protocols as well as the study design and limitations.

Results

A total of eight studies fulfilled the inclusion criteria and were included in the analysis. Types of procedures evaluated with ERAS protocols included tonsillectomy and adenoidectomy, functional endoscopic sinus surgery, tympanoplasty and mastoidectomy, and septoplasty. A reduction in postoperative length of stay and hospital costs was reported in two and three studies, respectively. Comparative studies between ERAS and control groups showed persistent improvement in pre‐ and postoperative anxiety and pain levels, without an increase in postoperative complications and readmission rates.

Conclusions

A limited number of studies discuss implementation of ERAS protocols for outpatient operations in otolaryngology. These clinical pathways appear promising for these procedures as they may reduce length of stay, decrease costs, and improve pain and anxiety postoperatively.
Transition to extrauterine life and the modeling of perinatal asphyxia in rats
Authors: Ortiz Mauro , Loidl Fabián , Vázquez‐Borsetti Pablo
Published: June 2022

Generation of murine models for the study of birth‐related pathologies has proven to be a complex and controversial problem. Differences in the relative timing of developmental events of both species have led some researchers to suggest that the rat is born comparatively less developed than the human. The solution proposed to this problem would consist in the delay of the experiments of perinatal asphyxia (PA), usually up to 7–10 days, allowing developmental levels to “equalize” with the human at birth. This solution generates a new set of problems. The developmental milestones in both species follow a divergent temporal pattern. Increasing the age of the rat not only can improve resemblance with humans but also will make the model miss a crucial set of milestones related to birth. During this process, there are specific mechanisms to protect the fetus from neuronal damage, especially those caused by asphyxia. These factors are not present in models where the asphyxia is delayed. In these models, there will be more false positives and more damage that would not be present in humans exposed to PA.

This article is categorized under:

Cancer > Stem Cells and Development

Congenital Diseases > Environmental Factors

Neurological Diseases > Environmental Factors
Ideal treatment timing of orthodontic anomalies—a German clinical S3 practice guideline
Authors: Kirschneck Christian , Proff Peter , Lux Christopher
Published: June 2022

Purpose

Ideal treatment timing in orthodontics is controversially discussed depending on the type and extent of the dysgnathia and malocclusion present, especially with regard to efficiency, patient burden and treatment efforts of early compared to regular or late treatment. This German clinical practice guideline aims to clarify, at which time points an orthodontic anomaly can be effectively treated and how treatment efficiency differs depending on treatment timing.

Methods

A systematic literature search was performed in various guideline databases and databases PROSPERO, MEDLINE (PubMed), Cochrane Library, Web of Science, ClinicalTrials.gov and the International Clinical Trials Registry Platform according to a predefined PICO (Population, Intervention, Comparison and Outcomes with added qualitative search terms) search algorithm and strategy. Appraisal of scientific evidence of the individual studies checked for eligibility was carried out according to SIGN (Scottish Intercollegiate Guidelines Network), AMSTAR II (Assessing the Methodological Quality of Systemic Reviews), and AXIS (Appraisal Tool to Assess the Quality of Cross-sectional Studies) tools. Only controlled studies with a high, acceptable or moderate quality (and thus an acceptable risk of bias) were considered.

Results

A total of 309 studies of over 11,000 sources screened were identified to be eligible for inclusion and critically appraised for study quality and risk-of-bias. No relevant guidelines relating to the aims of the present guideline were found. Elected delegates of in total 21 German scientific societies and organizations agreed upon a total of 19 evidence-based statements and recommendations based on a nominal consensus process.

Conclusions

Although most malocclusions can be effectively treated both in the early, late mixed, and permanent dentition, evidence suggests that therapy of a pronounced skeletal or dental class II anomaly can be started early to reduce the risk of dental anterior tooth trauma, whereas in a moderate class II anomaly, therapy can preferably be carried out before or during the pubertal growth peak. Therapy of a skeletal or dental class III anomaly should be started early, as this also reduces the need for later surgery to correct the anomaly. The treatment of a pronounced skeletal or dental transverse anomaly should be started early in the upper jaw in order to utilize the high adaptivity of the maxillary structures in young patients.