bluuebunny/crossref_metadata_2025 huggingface dataset:
Reactions of Ferrocenium Hexafluorophosphate with P−OR Nucleophiles Give Ring C−H Functionalization or Ring Replacement Products Depending on the Phosphorus Reagent
Authors: Chamkin Aleksandr A. , Krivykh Vasily V. , Kreindlin Arkady Z. , Dolgushin Fedor M. , Ustynyuk Nikolai A.
Published: March 2021

Ferrocenium hexafluorophosphate reacts with different P−OR nucleophiles (PR3) in CH2Cl2 at room temperature to give either half‐sandwich complexes [CpFe(PR3)3](PF6) (PR3=P(OMe)3, P(OEt)3, PhP(OMe)2) or ferrocenylphosphonium salts [CpFe(C5H4PR3)](PF6) (PR3=iPr2P(OMe), iPr2P(OEt)). Mixtures of both products are formed for some other nucleophiles (PR3=Ph2P(OMe), Ph2P(OEt), PhP(OiPr)2). The mechanism of the former reaction was established using DFT calculations. This reaction pathway is especially characteristic of π‐acceptor nucleophiles, which is presumably explained by their ability to stabilize the 19e intermediates. The result of the reaction with tertiary phosphines, aminophosphines, and P−OR nucleophiles can be reliably predicted based on the values of the Tolman electronic parameter (below 2070 cm−1 – only ferrocenylphosphonium salt, in between 2073 cm−1 and 2080 cm−1 – only half‐sandwich complex, and in the range from 2070 cm−1 to 2073 cm−1 – mixtures of both products).
Precision length determination and in silico simulation in PCR of microsatellite repeat sequences
Authors: Shioi Seijiro , Shimamoto Akiyoshi , Nakagami Yuki , Qin Lexin , Shimokawa Mototsugu , Oda Shinya
Published: March 2021

Despite being commonplace, polymerase chain reactions (PCRs) still contain many unknown aspects. One example is microsatellite PCR, which is now widely used for various purposes from ecology to cancer medicine. Since this category of repetitive DNA sequences induces polymerase slippage not only in vivo but also in vitro, microsatellite PCR products comprise a complex combination of DNA fragments with various lengths and have, therefore, been empirically interpreted. The primary obstacle for understanding microsatellite PCR was the intrinsic inaccuracy in sizing of DNA fragments in capillary electrophoresis (CE), which, however, has been overcome by elucidating intrinsic sizing errors in each fragment length range. Secondly, the slippage properties of the thermostable polymerases were first clarified in detail using primer extension assays. Furthermore, using the obtained slippage parameters and our original program, we have first reconstructed microsatellite PCR in silico. The entire processes of complex microsatellite PCR have, thus, been more clearly understood.
Alveolinids from the Lower Indus Basin, Pakistan (Eastern Neo‐Tethys): Systematic and biostratigraphic implications
Authors: Rahman Maqsood Ur , Hanif Muhammad , Jiang Tao , Wahid Sohail
Published: March 2021

The alveolinid group of larger benthic foraminifera has been vastly studied in western and central Neo‐Tethys, but less well analysed in eastern Neo‐Tethys. In this study, 19 Ypresian (Ilerdian–Cuisian) and Early Lutetian species of Alveolina have been identified and their biometrics, taxonomy, and biostratigraphic correlation with western and central Neo‐Tethys discussed. The Taxa of Early Ypresian age (SBZ5‐9) includes Alveolina vredenburgi, A. dedolia, A. subpyrenaica, A. cf. subpyrenaica, A. moussoulensis, A. aragonensis, A. decipiens, A. cylindrata, and A. ilerdensis. The Late Ypresian age (SBZ10‐12) taxa includes A. ruetimeyeri A. oblonga, A. haymanensis, A. lehneri, A. cosinensis cosigena, A. aff. frumentiformis, A sp. aff. A. azzarolii, and A. elliptica. The Early Lutetian age (SBZ13) taxa include A. stercusmuris and A. keili. The identified species have a close affinity to those reported from other areas of the Tethyan realm. However, some of these Alveolina species are considered to have stratigraphic ranges longer than formerly reported. The first appearance of A. ilerdensis (SBZ8‐10) is recorded earlier in SBZ7. The first appearance of A. ruetimeyeri (SBZ10‐11) is recorded earlier in SBZ‐9. The study provides more evidence for understanding the evolution of the Alveolina species and their biostratigraphic distribution in the eastern Tethyan realm.
Coenzyme Q10 inhibits RANKL‐induced osteoclastogenesis by regulation of mitochondrial apoptosis and oxidative stress in RAW264.7 cells
Authors: Zheng Delu , Cui Chenli , Shao Chen , Wang Yanqiu , Ye Chengsong , Lv Gaoyou
Published: March 2021

Coenzyme Q10 (CoQ10) has been reported to improve bone density and the number of trabeculae in postmenopausal osteoporosis, but the mechanism remains to be elucidated. We aimed to investigate the effects of CoQ10 on receptor activator of NF‐κB ligand (RANKL)‐induced osteoclastogenesis and the underlying molecular mechanisms. RAW264.7 cells were treated with different concentrations of RANKL to differentiate into osteoclasts, and then these cells were treated with different concentrations of CoQ10 with or without H2O2. Tartrate‐resistant acid phosphatase staining was performed to detect osteoclasts. Cell viability was tested by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay, cell apoptosis was examined by flow cytometry, and the effects of CoQ10 on protein and messenger RNA expression of mitochondrial apoptosis‐associated proteins and osteoclast marker proteins were measured by quantitative reverse transcription polymerase chain reaction and western blot, respectively. Furthermore, enzyme‐linked immunosorbent assay was conducted to analyze the activities of malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT). RANKL significantly induced osteoclastogenesis in RAW264.7 cells, with the greatest efficiency at 50 ng/ml. CoQ10 had no significant effects on cell viability but it significantly increased the percentages of cell apoptosis. Mechanically, CoQ10 statistically decreased the levels of Bcl‐2 and cytochrome C in mitochondria and upregulated the levels of Bax, cleaved caspase 3, and cytochrome C in the cytoplasm. Moreover, CoQ10 significantly decreased RANKL‐induced osteoclastogenesis regardless of exposure to H2O2. In addition, CoQ10 statistically reduced MDA activity and elevated the activities of SOD and CAT, as well as the expression of oxidative stress‐related proteins. CoQ10 may inhibit RANKL‐induced osteoclastogenesis by regulation of mitochondrial apoptosis and oxidative stress in RAW264.7 cells.
STAT3 activation in microglia exacerbates hippocampal neuronal apoptosis in diabetic brains
Authors: Yun Jang‐Hyuk , Lee Da‐Hye , Jeong Han‐Seok , Kim Hye Sun , Ye Sang‐Kyu , Cho Chung‐Hyun
Published: March 2021

Diabetes mellitus (DM) characterized by hyperglycemia leads to a variety of complications, including cognitive impairment or memory loss. The hippocampus is a key brain area for learning and memory and is one of the regions that is most sensitive to diabetes. However, the pathogenesis of diabetic neuronal lesion is not yet completely understood. We focused on the association of microglia activation and brain lesions in diabetes. In this study, we investigated whether and how signal transducer and activator of transcription 3 (STAT3) activation in microglia affects neuronal lesions in diabetic brains. Using a streptozotocin‐induced type 1 DM model, we showed enhanced hippocampal neuronal apoptosis that was associated with increased STAT3 activation. We found that hyperglycemia increased the expression of inflammatory cytokines such as interferon‐γ (IFN‐γ) and interleukin‐6, in the diabetic hippocampus. In particular, IFN‐γ induced autocrine activation of microglia, and STAT3 activation is important for this process. We also demonstrated that STAT3 activation in microglia increased tumor necrosis factor‐α (TNF‐α) expression; subsequently, TNF‐α increased neuronal apoptosis by increasing reactive oxygen species (ROS) levels in the neuronal cells. We also took advantage of mice lacking STAT3 in microglia and demonstrated that depletion of microglial STAT3 reduced neuronal apoptosis in the diabetic hippocampus. Taken together, these results suggest that STAT3 activation in microglia plays an important role in hyperglycemia‐induced neuronal apoptosis in the diabetic hippocampus and provide a potential therapeutic benefit of STAT3 inhibition in microglia for preventing diabetic neuronal lesions.
Gift Recipients’ Beliefs About Occasion‐based and Nonoccasion‐based Gifts: The Importance of Signaling Care and Meeting Expectations in Gift Giving
Authors: Givi Julian , Galak Jeff
Published: March 2021

Most gifts are occasion‐based as opposed to nonoccasion‐based. That is, most gifts are given in the presence of a special occasion, rather than in the absence of one. Across a series of scenario‐based studies, the present research demonstrates that, despite occasion‐based gifts being much more common, recipients anticipate that their happiness levels will be quite high when receiving nonoccasion‐based gifts, varying little with gift quality. In contrast, they anticipate that their happiness levels will not always be high when receiving occasion‐based gifts, varying greatly with gift quality. These diverging outcomes arise because the caliber of gift that is required to signal care and thus meet a recipient’s expectation is much lower for nonoccasion‐based gifts than for occasion‐based ones. Critically, givers misforecast recipients’ anticipated positive reactions to nonoccasion‐based gifts, helping to explain why these gifts are, unfortunately, rather rare.
MOG antibody‐positive cerebral cortical encephalitis: Two case reports and literature review
Authors: Tian Fei , Liu Xuejun , Yang Chengqing , Wang Bingbing , Song Zhenfeng , Zhang Ying
Published: March 2021

Objective

To investigate the clinical and MRI features of myelin oligodendrocyte glycoprotein (MOG) antibody‐positive cerebral cortical encephalitis.

Methods

To summarize the clinical manifestations, magnetic resonance imaging (MRI) features, and diagnosis and treatment of two children diagnosed with MOG antibody‐positive cortical encephalitis in our hospital, and to analyze all of the literature on MOG antibody‐positive associated cerebral cortical encephalitis published in the last 10 years.

Results

A total of 24 patients, 20 adults, and 4 children were included. The main symptoms of all observed patients were as follows: seizures 20/24 (83%), headache 18/24 (75%), fever 13/24 (54%), and increased cell number in cerebrospinal fluid 22/24 (92%). The main radiological sign was enhanced FLAIR signal in cortical 24/24 (100%), including enhanced fluid‐attenuated inversion recovery (FLAIR) signal in unilateral cortical 20/24 (83%).

Conclusions

The clinical manifestations of MOG antibody‐positive cerebral cortical encephalitis are complex and varied, and long‐term follow‐up is needed to clarify the prognosis and recurrence, providing reference for the clinical treatment.
Functional conservation and divergence of color‐pattern‐related agouti family genes in teleost fishes
Authors: Liang Yipeng , Grauvogl Maximilian , Meyer Axel , Kratochwil Claudius F.
Published: March 2021

While color patterns are highly diverse across the animal kingdom, certain patterns such as countershading and stripe patterns have evolved repeatedly. Across vertebrates, agouti‐signaling genes have been associated with the evolution of both patterns. Here we study the functional conservation and divergence by investigating the expression patterns of the two color‐pattern‐related agouti‐signaling genes, agouti‐signaling protein 1 (asip1) and agouti‐signaling protein 2b (asip2b, also known as agrp2) in Teleostei. We show that the dorsoventral expression profile of asip1 and the role of the “stripe repressor” asip2b are shared across multiple teleost lineages and uncover a previously unknown association between stripe–interstripe patterning and both asip1 and asip2b expression. In some species, including the zebrafish (Danio rerio), these two genes show complementary and overlapping expression patterns in line with functional redundancy. Our results thus suggest how conserved and novel functions of agouti‐signaling genes might have shaped the evolution of color patterns across teleost fishes.
Germline evaluation of patients undergoing tumor genomic profiling: An academic cancer center’s experience with implementing a germline review protocol
Authors: Stachowiak Samantha , Jacquart Amanda , Zimmermann Michael T. , George Ben , Dong Huaying , Geurts Jennifer L.
Published: March 2021

Tumor genomic profiling (TGP) has the potential to identify germline variants in addition to its primary use of informing cancer treatment based on genetic alterations within the tumor. However, there are no formal consensus guidelines to identify patients who would be eligible for genetic counseling (GC) and germline testing (GT) testing in patients undergoing TGP. The purpose of this study is to describe an institutionally developed Germline Review Protocol (GRP) to evaluate adult cancer patient cases already undergoing TGP to determine GC referral eligibility. We report on our retrospective experience implementing this protocol into practice wherein 172 patients out of 638 patients reviewed (27%) were recommended for a GC referral over a 17‐month time period. Of those 172 patients recommended for a GC referral, only 34 patients (20%) completed GC and GT. Among patients who received GT, 15 (44%) were positive for at least one pathogenic or likely pathogenic (P/LP) variant, seven patients (21%) were negative and 12 patients (35%) had at least 1 variant of uncertain significance (VUS). The primary reason GC and GT was not completed was because the patient moved to hospice care or was deceased. This is one of the first studies outlining the process and results of a formalized institutional protocol to facilitate patient referrals for GC and GT based on TGP results.
ACE2 models of frequently contacted animals provide clues of their SARS‐CoV‐2 S protein affinity and viral susceptibility
Authors: Ma Cheng , Gong Caixia
Published: March 2021

The outbreak of atypical pneumonia (coronavirus disease 2019 [COVID‐19]) has been a global pandemic and has caused severe losses to the global economy. The virus responsible for COVID‐9, severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), has a spike glycoprotein (S protein) that binds angiotensin‐converting enzyme 2 (ACE2) present on host cell membranes to gain entry. Based on the full‐length human ACE2 cryo‐EM structure, we generated homology models of full‐length ACE2 proteins from various species (gorilla, monkey, pig, bovine, sheep, cat, dog, mouse, and rat). Although these ACE2 molecules were found to share similar overall structures, their S–ACE2 interface residues differed. These differences likely result in variations in the ACE2 binding affinities to the SARS‐CoV‐2 S protein. The highest affinities are predicted for human, gorilla, and monkey, while mouse and rat ACE2 are predicted to have the lowest affinities. Cat ACE2 is predicted to have a lower S protein affinity than dog ACE2. Although affinity is not the only factor that affects viral susceptibility, it is one of the most important factors. Thus, we believe that care should be taken with these animals to prevent the spread of SARS‐CoV‐2 among animal and human populations.
Outcomes among 10,314 hospitalized COVID‐19 patients at a tertiary care government hospital in Delhi, India
Authors: Malhotra Vikas , Basu Saurav , Sharma Nandini , Kumar Suresh , Garg Sandeep , Dushyant Kumar , Borle Amod
Published: March 2021

A significant proportion of patients with coronavirus disease 2019 (COVID‐19) require timely hospitalization to reduce the risk of complications and mortality. We describe the trends of the age and gender stratified outcomes among hospitalized COVID‐19 patients with moderate to severe illness at the largest dedicated tertiary care COVID‐19 government hospital in New Delhi, India. A retrospective cohort study through secondary data analysis from in‐patient hospital data of patients admitted from April 1 to November 15, 2020 was conducted. The data of 10,314 laboratory‐confirmed patients with COVID‐19 was analyzed, of which 8899 (86.28%) were discharged after recovery, and 1415 (13.72%) died. The mean (SD) age of the hospitalized patients was 46.43 (18.74) years (n = 10,309) including 6031 (58.50%) male and 4278 (41.50%) female patients (n = 10,309). On bivariate analysis, increasing age was associated with significantly higher odds of mortality in both gender (p < .001). The mortality rate in female patients was lower (11.92%) compared with male patients (15.75%) (p = .675). However, elderly women had the highest odds of mortality (p < .001), indicating the possible role of delayed health seeking behavior, secondary to familial, and social neglect. Mortality in the patients with COVID‐19 also occurred early after admission suggesting rapid deterioration, delayed reporting by patients, or their late referral from other health facilities. However, the overall statewide recovery rate showed steady improvement since the onset of the pandemic. In contrast, the recovery rate among the moderate‐severe cases that were hospitalized at this tertiary care center during the same period reflected a lower nonspecific zigzag pattern indicating limited effectiveness of the COVID‐19 treatment regimens.
pT3 N0 Laryngeal Squamous Cell Carcinoma: Oncologic Outcomes and Prognostic Factors of Surgically Treated Patients
Authors: Mattioli Francesco , Fermi Matteo , Molinari Giulia , Capriotti Vincenzo , Melegari Gabriele , Bertolini Federica , D'Angelo Elisa , Tirelli Giancarlo , Presutti Livio
Published: March 2021

Objectives/Hypothesis

To assess the disease control, survival rates, and prognostic factors of exclusive surgical treatment for patients with pT3 N0 laryngeal squamous cell carcinoma (LSCC).

Study Design

Multicentric retrospective cohort study.

Methods

Multicentric retrospective case series of previously untreated patients with pT3 R0N0 LSCC, who received exclusive surgery between 2011 and 2019. Tumor location; subsite involvement; grading; and lymphatic, vascular, and perineural invasion were reported. Overall survival (OS), disease‐specific survival (DSS), and disease‐free survival (DFS) were measured.

Results

Fifty‐four patients (mean age 67.1; male sex 83.3%; mean follow‐up period 37 months) underwent total laryngectomy (48.1%) or partial laryngectomy (51.9%). Ipsilateral or bilateral neck dissection was performed in 46 (85.2%) cases. Perineural invasion was more frequent in case of supraglottic involvement than glottic involvement (85.7% vs. 14.3%, P = .03). Five (9.3%) patients experienced recurrence (3 local recurrences, 1 nodal recurrence, 1 distant recurrence). Rate of recurrence differed between glottic (0%), supraglottic (80%), and transglottic (20%) tumors (P = .01), with a lower risk yielded by glottic involvement (odds ratio [OR], 0.05, 95% confidence interval [95% CI], 0.01–0.56, P = .01). A higher risk was recorded in case of perineural invasion (OR, 66.0, 95% CI, 1.41–3085.3, P = .03). The OS, DSS, and DFS were 79.6%, 96.3%, and 90.7%, without differences regarding the type of surgery. The DFS was lower in case of supraglottic involvement when compared to purely glottic LSCC (83.9% vs. 100%, P = 0.02).

Conclusions

Exclusive surgery is a safe option for patients with pT3 R0N0 LSCC. Adjuvant treatments or closer follow‐up monitoring might be considered in case of supraglottic involvement or perineural invasion.

Level of Evidence

4 Laryngoscope, 131:2262–2268, 2021
Improving peer‐review by developing reviewers' feedback literacy
Authors: Chong Sin Wang
Published: March 2021

Key points

There is a need to train journal peer reviewers to provide professional, constructive, and actionable feedback: i.e., develop their feedback literacy.

Journals and publishers can improve the way they support peer reviewers' feedback literacy by raising awareness and providing guidance and exemplars of good practice.

Existing online peer‐review training resources developed by major publishers only focus on content of feedback but neglect the socio‐emotional aspect of feedback.

Resources to develop peer reviewers' feedback literacy should be formulated by adopting knowledge‐based, skills‐based, and community‐based approaches.
N6‐Methyladenosine (m6A) readers are dysregulated in renal cell carcinoma
Authors: von Hagen Felix , Gundert Larissa , Strick Alexander , Klümper Niklas , Schmidt Doris , Kristiansen Glen , Tolkach Yuri , Toma Marieta , Ritter Manuel , Ellinger Jörg
Published: March 2021

N6‐Methyladenosine (m6A) is the most common modification of messenger RNA (mRNA) in mammals. It critically influences RNA metabolism and plays an essential role in virtually all types of bioprocesses including gene expression, tissue development, self‐renewal and differentiation of stem cells, stress response and circadian clock control. It plays a crucial role in carcinogenesis and could be used as a prognostic and a diagnostic tool and as a target for new anticancer therapies. m6A modification is dynamically and reversibly regulated by three types of proteins. Methyltransferases, so‐called “writers” add a methyl group to the adenosine, which can be removed by demethylases, also called “erasers.” m6A‐specific RNA‐binding proteins, from here on referred to as “readers,” preferentially bind to the m6A site and mediate biological functions, such as translation, splicing or decay of RNA. In this study, we examined the expression of the six m6A readers HNRNPA2B1, HNRNPC, YTHDC1 and YTHDF1‐3 in clear cell renal carcinoma (ccRCC). We show that on mRNA level the expression of all six m6A readers is significantly downregulated compared to normal renal tissue and on protein level five out of six readers are dysregulated. Lower levels of some m6A readers are correlated with advanced stage and grade as well as associated with a shorter overall, progression‐free and cancer‐specific survival. In summary, we could show that m6A readers are dysregulated in ccRCC and might therefore act as a tumor marker, could give further information on the individual prognosis and be a target of innovative cancer therapy.
Nonlinear modulation ofCOVID‐19 transmission by climate conditions
Authors: Gao Meng , Zhou Qiming , Yang Xian , Li Qingxiang , Zhang Shiqing , Yung Ken Kin Lam , Guo Yike
Published: March 2021

COVID‐19 is spreading rapidly worldwide, posing great threats to public health and economy. This study aims to examine how the transmission of COVID‐19 is modulated by climate conditions, which is of great importance for better understanding of the seasonal feature of COVID‐19. Constrained by the accurate observations we can make, the basic reproduction numbers (R0) for each country were inferred and linked to temperature and relative humidity (RH) with statistical analysis. UsingR0as the measure of COVID‐19 transmission potential, we find stronger transmission of COVID‐19 under mildly warm (0°C <T< 20°C) and humid (RH > 60%) climate conditions, while extremely low (T< −2°C) and high (T> 20°C) temperature or a dry climate (RH < 60%) weakens transmission. The established nonlinear relationships between COVID‐19 transmission and climate conditions suggest that seasonal climate variability may affect the spread and severity of COVID‐19 infection, and temperate coastal regions with mildly warm and humid climate would be susceptible to large‐scale outbreaks.
Anti‐Obesity Effect ofT. ChebulaFruit Extract on High Fat Diet Induced Obese Mice: A Possible Alternative Therapy
Authors: Subramanian Gowtham , Shanmugamprema Deepankumar , Subramani Ramya , Muthuswamy Karthi , Ponnusamy Vinithra , Tankay Kalpana , Velusamy Thirunavukkarasu , Krishnan Vasanth , Subramaniam Selvakumar
Published: March 2021

Occurrence of obesity and its associated metabolic disorders continues to escalate. The present study evaluates the anti‐obesity effects of ethanolic fruit extract ofTerminalia chebula(EETC) on high fat diet induced obese mice. The bioactive compounds present in the EETC is evaluated by Fourier‐transform infrared (FT‐IR), Gas chromatography‐mass spectrometry (GC‐MS), and Liquid chromatography‐mass spectrometry (LC‐MS) analysis. The effects of EETC on energy intake, glucose tolerance, and various biochemical parameters were analyzed using laboratory mice. Relative gene expression of Fatty acid synthase (FAS), Peroxisome proliferator‐activated receptors α (PPARα), Carnitine palmitoyltransferase‐1 (CPT‐1), Tumor necrosis factor alpha (TNF‐α) as well as Interleukin 6 (IL‐6) were analyzed in liver and adipose tissues. The findings reveal the hypolipidemic and anti‐obesity potential of EETC on high fat fed obese mice. EETC exerts its anti‐obesity effects by suppressing lipogenesis through reduction in lipogenic enzyme (FAS) expression, increased fatty acid oxidation via PPARα and CPT‐1 and by triggering the anti‐inflammatory responses. To our knowledge, this is the first report of the effect of EETC on PPARα and CPT‐1 in in vivo.
Superoxide free radical spin‐lattice relaxivity: A quench‐assisted MR study
Authors: MacKinnon Martin J. , Berkowitz Bruce A. , Shih Yen‐Yu Ian
Published: March 2021

Purpose

QuEnch‐assiSTed (QUEST) MRI provides a unique biomarker of excessive production of paramagnetic free radicals (oxidative stress) in vivo. The contribution from superoxide, a common upstream species found in oxidative stress‐based disease, to the QUEST metric is unclear. Here, we begin to address this question by measuring superoxide spin‐lattice relaxivity (r1) in phantoms.

Methods

Stable superoxide free radicals were generated in water phantoms of potassium superoxide (. To measure r1, 1/T1 of different concentration solutions of KO2 in the presence and absence of the antioxidant superoxide dismutase were measured. The 1/T1 confounding factors including acquisition sequence, pH, and water source were also evaluated.

Results

The T1‐weighted signal intensity increased with KO2 concentration. No contribution from pH, or reaction products other than superoxide, noted on 1/T1. Superoxide r1 was measured to be 0.29 mM−1 s−1, in agreement with that reported for paramagnetic molecular oxygen and nitroxide free radicals.

Conclusion

Our first‐in‐kind measurement of superoxide free radical r1 suggests a detection sensitivity of QUEST MRI on the order of tens of μM, within the reported level of free radical production during oxidative stress in vivo. Similar studies for other common free radicals are needed.
Ultrashort echo time Cones double echo steady state (UTE‐Cones‐DESS) for rapid morphological imaging of short T2 tissues
Authors: Jang Hyungseok , Ma Yajun , Carl Michael , Jerban Saeed , Chang Eric Y. , Du Jiang
Published: March 2021

Purpose

In this study, we aimed to develop a new technique, ultrashort echo time Cones double echo steady state (UTE‐Cones‐DESS), for highly efficient morphological imaging of musculoskeletal tissues with short T2s. We also proposed a novel, single‐point Dixon (spDixon)‐based approach for fat suppression.

Methods

The UTE‐Cones‐DESS sequence was implemented on a 3T MR system. It uses a short radiofrequency (RF) pulse followed by a pair of balanced spiral‐out and spiral‐in readout gradients separated by an unbalanced spoiling gradient in‐between. The readout gradients are applied immediately before or after the RF pulses to achieve a UTE image (S+) and a spin/stimulated echo image (S−). Weighted echo subtraction between S+ and S− was performed to achieve high contrast specific to short T2 tissues, and spDixon was applied to suppress fat by using the intrinsic complex signal of S+ and S−. Six healthy volunteers and five patients with osteoarthritis were recruited for whole‐knee imaging. Additionally, two healthy volunteers were recruited for lower leg imaging.

Results

The UTE‐Cones‐DESS sequence allows fast volumetric imaging of musculoskeletal tissues with excellent image contrast for the osteochondral junction, tendons, menisci, and ligaments in the knee joint as well as cortical bone and aponeurosis in the lower leg within 5 min. spDixon yields efficient fat suppression in both S+ and S− images without requiring any additional acquisitions or preparation pulses.

Conclusion

The rapid UTE‐Cones‐DESS sequence can be used for high contrast morphological imaging of short T2 tissues, providing a new tool to assess their association with musculoskeletal disorders.
Evaluation of a Random Forest Model to Identify Invasive Carp Eggs Based on Morphometric Features
Authors: Goode Katherine , Weber Michael J. , Matthews Aaron , Pierce Clay L.
Published: March 2021

Three species of invasive carp—Grass Carp Ctenopharyngodon idella, Silver Carp Hypophthalmichthys molitrix, and Bighead Carp H. nobilis—are rapidly spreading throughout North America. Monitoring their reproduction can help to determine establishment in new areas but is difficult due to challenges associated with identifying fish eggs. Recently, random forest models provided accurate identification of eggs based on morphological traits, but the models have not been validated using independent data. Our objective was to evaluate the predictive performance of egg identification models developed by Camacho et al. (2019) for classifying invasive carp eggs by using an independent data set. When invasive carp were grouped as one category, predictive accuracy was high at the following levels: family (89%), genus (90%), species (91%), and species with reduced predictor variables (94%). Invasive carp predictive accuracy decreased when we only considered observations from newly sampled locations (family: 9%; genus: 22%; species: 30%; species with reduced predictor variables: 70%), suggesting potential differences in egg characteristics among locations. Random forest models using a combination of previous and new data resulted in high predictive accuracy for invasive carp (96–98%) when invasive carp were grouped as one class for all models at the family, genus, and species levels. The two most influential predictor variables were average membrane diameter and average embryo diameter; the probability of predicting an invasive carp egg increased with these metrics. High predictive accuracy metrics suggest that these trained and validated random forest models can be used to identify invasive carp eggs based on morphometric variables. However, decreased performance at new locations suggests that more research would be beneficial to determine the models’ applicability to a larger spatial region.
Higher‐order explicit schemes based on the method of characteristics for hyperbolic equations with crossing straight‐line characteristics
Authors: Lakoba Taras I. , Jewell Jeffrey S.
Published: March 2021

We develop method of characteristics schemes based on explicit Runge–Kutta and pseudo‐Runge–Kutta third‐ and fourth‐order solvers along the characteristics. Schemes based on Runge–Kutta solvers are found to be strongly unstable for certain physics‐motivated models. In contrast, schemes based on pseudo‐Runge–Kutta solvers are shown to be only weakly unstable for periodic boundary conditions and essentially stable for the more physically relevant nonreflecting boundary conditions. Our implementation of nonreflecting boundary conditions does not rely on interpolation.
Improving mechanical properties and fretting wear resistance of ultra‐high‐molecular‐weight‐polyethylene via incorporation of zeolitic imidazolate frameworks‐carbon nano‐fiber
Authors: Xin Xiaocui , Wang Yunxia , Meng Zhaojie , Yan Fengyuan
Published: March 2021

Zeolitic imidazolate frameworks (denoted as ZIF8) were combined with carbon nano‐fiber (denoted as CNF) by a facile liquid‐phase chemical route to afford ZIF8‐CNF nano‐hybrid as the filler of ultra‐high‐molecular‐weight‐polyethylene (abridged as UHMWPE). The as‐prepared ZIF8‐CNF nano‐filler was incorporated into UHMWPE matrix via hot pressing to obtain the UHMWPE‐matrix composite. The effects of CNF, ZIF8, and ZIF8‐CNF on the thermal stability, mechanical properties, and fretting wear behavior of UHMWPE were comparatively investigated based on thermogravimetric analysis‐differential scanning calorimetry, scanning electron microscopy, X‐ray diffraction, and stress–strain testing. Findings indicate that ZIF8‐CNF can significantly promote the crystallization of UHMWPE and improve its thermal stability and mechanical properties. Besides, the high interfacial strength between the ZIF8‐CNF nano‐filler and UHMWPE matrix is favorable for facilitating the transfer of load from the polymer matrix to the inorganic filler and for the formation of transfer film on worn steel surface, thereby alleviating adhesion, abrasion, and plastic deformation. Therefore, the ZIF8‐CNF/UHMWPE composite exhibits much better fretting wear resistance than neat UHMWPE, CNF/UHMWPE composite, and ZIF8/UHMWPE composite.
Single daily dosing versus divided dosing intravenous ondansetron to prevent chemotherapy‐induced nausea and vomiting among children: A comparative randomized double‐blind controlled trial
Authors: Ruktrirong Jittra , Traivaree Chanchai , Monsereenusorn Chalinee , Photia Apichat , Lertvivatpong Nawachai , Rujkijyanont Piya
Published: March 2021

Background

Chemotherapy‐induced nausea and vomiting (CINV) is a common complication in cancer treatment. Ondansetron is an effective antiemetic drug widely used to prevent CINV; however, the effective administrative dosing strategies among pediatrics remain unclear. The study aimed to investigate clinical effectiveness of single daily dosing versus divided dosing ondansetron.

Methods

In all, 194 children undergoing chemotherapy were randomized to receive either single daily dosing (0.3 mg/kg/dose) or divided dosing (0.15 mg/kg/dose every 8 hours) intravenous ondansetron for 24 hours. Clinical parameters including number of emesis episodes, nausea scores, appetite levels, parent's satisfaction, and adverse effects within 24 hours were analyzed.

Results

No significant differences were found between the two dosing strategies concerning number of emesis episodes and parent's satisfaction. However, nonleukemic hematologic malignancies and concurrent administration of intrathecal methotrexate–hydrocortisone–cytarabine (IT‐MHA) were associated with increased risk of acute‐phase vomiting. Interestingly, none of the patients aged under 7 years, receiving divided dosing ondansetron, presented nausea symptoms compared with those receiving single daily dosing (p‐value .034). No significant differences regarding headache were observed between the two dosing strategies and none of the patients experienced QTc prolongation.

Conclusion

Ondansetron administered as divided dosing should be considered among children aged under 7 years to prevent chemotherapy‐induced nausea and among patients receiving low emetogenic chemotherapy to maintain their appetite. Both administrative dosing strategies were well tolerated with no significant adverse effects.
Diagnostic utility of MDCT in evaluation of persistent stridor in children: Large airway causes and benefit of additional findings
Authors: Sodhi Kushaljit S. , Rana Pratyaksha , Bhatia Anmol , Saxena Akshay K. , Mathew Joseph L. , Winant Abbey J. , Lee Edward Y.
Published: March 2021

Objectives

To assess the diagnostic utility of MDCT in the evaluation of persistent stridor in children for the underlying large airway causes and benefit of additional findings.

Methods

All consecutive pediatric patients who underwent MDCT for the evaluation of persistent stridor from December 2018 to February 2020 were included. Two pediatric radiologists independently reviewed MDCT studies for the presence of abnormalities at six large airway levels: (1) nasopharynx, (2) oropharynx, (3) glottis, (4) subglottis, (5) trachea, and (6) mainstem bronchi. In addition, studies were evaluated for the presence of non‐airway abnormalities. Interobserver agreement between two reviewers was evaluated with kappa statistics.

Results

There were a total of 40 pediatric patients (age range: 1 day–4 years. MDCT detected large airway abnormalities in 20 (50%) out of 40 patients, including 4 (20%) in nasopharynx, 4 (20%) in glottis, 4 (20%) in trachea, 3 (15%) in subglottis, 3 (15%) in mainstem bronchi, and 2 (10%) in oropharynx. Non‐airway abnormalities were seen in 13 (32.5%) children, including 9 (69%) in the lungs, 3 (23%) in the soft tissue, and 1 (8%) in the bone. The remaining 7 (17.5%) studies were normal. There was excellent interobserver agreement seen for detecting large airway and non‐airway abnormalities (k > 0.90).

Conclusion

MDCT has high diagnostic utility in diagnosing large airway causes of persistent stridor in children. It can also provide additional information regarding non‐airway abnormalities. Therefore, MDCT has the potential to be utilized as a noninvasive problem‐solving imaging modality in pediatric patients with persistent stridor.
The improvement in continuity and integrity of survivorship care for breast cancer survivors in Chinese healthcare system
Authors: Lou Shuchang , Li Jun , Xu Dejing
Published: March 2021

Breast cancer is a major threat to human health. For a long term, breast cancer and the side effects of cancer treatments affect health and life quality of cancer survivors. With the development of medical technology for breast cancer in recent decades, the long‐term survival rate of breast cancer patients has been dramatically improved. There is an urgent need to identify and establish a health care model that could provide more customized, long‐term, and comprehensive medical services for breast cancer patients, especially for those in China. Multiple cancer survivorship care plans that have been widely used in Western countries, such as chronic care, shared care, and disease‐specific model, were summarized from original researches, systemic reviews, and health guidelines published by national and international health organizations. In currently available cancer survivorship care plans, oncology nurses played an indispensable significant role. But current existing cancer survivorship care plans could not be directly implemented in China due to different cultural backgrounds between Eastern and Western countries. Some adjustments and modifications need to be done on the basis of existing survivorship care plan to make it more suitable to Chinese patients' needs and with Chinese characteristics. For providing continuous and integrated high‐quality cancer survivorship care suitable for Chinese health care system, innovative technologies (telehealth, internet‐based symptom monitoring, mobile applications, etc.) could be rationally used as supplementary tools for current cancer survivorship care plans.
Nonparametric goodness‐of‐fit testing for parametric covariate models in pharmacometric analyses
Authors: Hartung Niklas , Wahl Martin , Rastogi Abhishake , Huisinga Wilhelm
Published: March 2021

The characterization of covariate effects on model parameters is a crucial step during pharmacokinetic/pharmacodynamic analyses. Although covariate selection criteria have been studied extensively, the choice of the functional relationship between covariates and parameters, however, has received much less attention. Often, a simple particular class of covariate‐to‐parameter relationships (linear, exponential, etc.) is chosen ad hoc or based on domain knowledge, and a statistical evaluation is limited to the comparison of a small number of such classes. Goodness‐of‐fit testing against a nonparametric alternative provides a more rigorous approach to covariate model evaluation, but no such test has been proposed so far. In this manuscript, we derive and evaluate nonparametric goodness‐of‐fit tests for parametric covariate models, the null hypothesis, against a kernelized Tikhonov regularized alternative, transferring concepts from statistical learning to the pharmacological setting. The approach is evaluated in a simulation study on the estimation of the age‐dependent maturation effect on the clearance of a monoclonal antibody. Scenarios of varying data sparsity and residual error are considered. The goodness‐of‐fit test correctly identified misspecified parametric models with high power for relevant scenarios. The case study provides proof‐of‐concept of the feasibility of the proposed approach, which is envisioned to be beneficial for applications that lack well‐founded covariate models.
Ultrafast Electron Transfer in Binary Nanoparticle Superlattices under High Pressure
Authors: Cheng Ji-Chao , Pan Ling-Yun , Tu Hong-Yu , Qi Hong-Jian , Ji Wen-Yu , Li Fang-Fei , Wang Ying-Hui , Xu Shu-Ping , Men Zhi-Wei , Cui Tian
Published: March 2021

The interparticle spacing of a heterostructure is a crucial factor affecting electron transfer (ET) process. Herein, binary nanoparticle superlattices (BNSLs) composed of CdSe/ZnS quantum dots (QDs) and Au nanoclusters (NCs) are prepared. Steady‐state and time‐resolved spectra illustrate that the ET accelerates as the pressure increases because pressure effectively adjusts the interparticle spacing. The results also demonstrate that the trap state of the CdSe/ZnS QDs affects the ET process of BNSLs.
GFS model fidelity in capturing the transition of low‐pressure area to monsoon depression
Authors: Sarkar Sahadat , Mukhopadhyay Parthasarathi , Dutta Somenath , Phani Murali Krishna R. , Kanase Radhika D. , Prasad V. S. , Deshpande Medha S.
Published: March 2021

Low‐pressure areas and monsoon depressions are the synoptic‐scale systems that contribute largely to the Indian summer monsoon rainfall. India Meteorological Department currently uses a high‐resolution (∼12 km) Global Forecasting System (GFS) model for short‐ and medium‐range operational forecasts over the Indian region. In this study, we have evaluated the performance of the GFS model in capturing the transition of low‐pressure areas (LPAs) to monsoon depressions (L2D). GFS has a good fidelity in capturing synoptic variance over the Indian region, and can simulate the composite precipitation structure for L2D cases. The upper‐level warm core temperature structure is prominent for L2D cases, while it is at the lower level for the cases where the LPA does not intensify and remains as low (RL) pressure area. GFS can simulate the upper‐level warm core temperature structure up to 24 hr. The model has good fidelity in capturing the upper‐level potential vorticity maxima for L2D cases but amplitude is underestimated as the lead time increases. GFS fails to reproduce the potential vorticity structure and amplitude for RL cases. Positive lower‐ to middle‐level heating to the west/southwest sector of the system is seen for L2D cases but the heating is at the lower level for RL cases. Heating structures for L2D cases are slightly underestimated by GFS but it fails to simulate the structure for RL cases. The model greatly underestimates the vertical velocity for L2D cases and RL cases with increasing lead time. Positive moisture convergence is seen at the lower level near the system centre. GFS underestimates the moisture convergence for both the cases and the southward tilt with height is also not captured well. GFS has good fidelity in simulating the dynamical parameters associated with L2D cases but shows lesser fidelity for RL cases.
Understanding the dependence of storm splitting on numerical models: Comparing UM and WRF
Authors: Dipankar Anurag , Rajagopalan Ragi , Huang Xiang‐Yu
Published: March 2021

This article performs a systematic study to understand the dependence of the splitting of an initially axisymmetric storm on the various components of the Unified Model (UM) and Weather Research and Forecasting model (WRF). The models are adapted to keep their differences at a minimum. Results at km‐scale grid resolution show that the models differ significantly even under a controlled environment with no surface and radiative forcing. The initial storm in UM splits into two within the first hour. WRF also produces two separate updraughts, but it does not split entirely because of a secondary downdraught that falls just ahead of the original updraught. The cold pool from this downdraught converges with the oncoming winds at lower levels to generate a ring of updraughts connecting the two. UM also shows a similar secondary downdraught, but it is relatively weak. Experiments with the successive reduction in complexity of the microphysics scheme show that the models start to differ with the inclusion of rain processes. Sensitivity experiments with the magnitude of turbulent mixing length do not impact this aspect of model behaviour. Resolution sensitivity experiments show that the storm does not split in UM for a horizontal resolution of O(100 m), whereas WRF behaves consistently across all the resolutions. Through further analyses, we argue that the formal accuracy of the model dynamical core has no control in deciding whether the initial storm will undergo a split or not.
A particle flow filter for high‐dimensional system applications
Authors: Hu Chih‐Chi , van Leeuwen Peter Jan
Published: March 2021

A novel particle filter proposed recently, the particle flow filter (PFF), avoids the long‐existing weight degeneracy problem in particle filters and, therefore, has great potential to be applied in high‐dimensional systems. The PFF adopts the idea of a particle flow, which sequentially pushes the particles from the prior to the posterior distribution, without changing the weight of each particle. The essence of the PFF is that it assumes the particle flow is embedded in a reproducing kernel Hilbert space, so that a practical solution for the particle flow is obtained. The particle flow is independent of the choice of kernel in the limit of an infinite number of particles. Given a finite number of particles, we have found that a scalar kernel fails in high‐dimensional and sparsely observed settings. A new matrix‐valued kernel is proposed that prevents the collapse of the marginal distribution of observed variables in a high‐dimensional system. The performance of the PFF is tested and compared with a well‐tuned local ensemble transform Kalman filter (LETKF) using the 1,000‐dimensional Lorenz 96 model. It is shown that the PFF is comparable to the LETKF for linear observations, except that explicit covariance inflation is not necessary for the PFF. For nonlinear observations, the PFF outperforms LETKF and is able to capture the multimodal likelihood behavior, demonstrating that the PFF is a viable path to fully nonlinear geophysical data assimilation.
Pornography and its impact on the sexual health of men
Authors: Kirby Mike
Published: March 2021

Increased internet access has been accompanied by increased numbers of adolescent and adult men viewing online pornography, and there is growing concern about how this may affect their sexual development, sexual function, mental health and intimate relationships. This paper briefly reviews men's relationship with porn and the possible impact on sexual function.
Sepsis: an important treatable illness, but susceptible to hype
Authors: Kirby Roger
Published: March 2021

Misunderstanding about sepsis, and misguided perceptions about treatment success rates, do a disservice to healthcare practitioners who, in the vast majority of cases, achieve the best possible outcomes for patients with life‐threatening infection.