bluuebunny/crossref_metadata_2025 huggingface dataset:
Programmable RNA N1‐Methyladenosine Demethylation by a Cas13d‐Directed Demethylase
Authors: Xie Shanshan , Jin Hao , Yang Feng , Zheng Hong , Chang Yongxia , Liao Ying , Zhang Ye , Zhou Tianhua , Li Yang
Published: June 2021

N1‐methyladenosine (m1A) is a prevalent and reversible RNA modification, which plays a crucial role in the regulation of RNA fate and gene expression. However, the lack of tools to precisely manipulate m1A sites in specific transcripts has hindered efforts to clarify the association between a specific m1A‐modified transcript and its phenotypic outcomes. Here we develop a CRISPR‐Cas13d‐based tool called reengineered m1A modification valid eraser (termed “REMOVER”) for targeted m1A demethylation of a specific transcript. The catalytically inactive RfxCas13d (dCasRx) is fused to the m1A demethylase ALKBH3, and the dCasRx‐ALKBH3 fusion protein can mediate potent demethylation of m1A‐modified RNAs. We further find that REMOVER can specifically demethylate m1A of MALAT1 and PRUNE1 RNAs, thereby significantly increasing their stability. Our study establishes REMOVER as a tool for targeted RNA demethylation of specific m1A‐modified transcripts, which enables further elucidation of the relationship between m1A modification of specific transcripts and their phenotypic outcomes.
Influence of V/P switchover point, injection speed, and holding pressure on quality consistency of injection‐molded parts
Authors: Huang Ming‐Shyan , Nian Shih‐Chih , Lin Guan‐Ting
Published: June 2021

During the injection molding of molten polymers, the control strategy is switched from speed control to pressure control at the filling‐to‐packing (V/P) switchover point. V/P switchover influences part quality and process stability. V/P switchover timing traditionally depends on the degree of volumetric filling of molten polymer in the cavity and is limited to obtain a smooth and repeatable pressure curve for each injection, indicating consistent part quality. Repeatability is affected by the V/P switchover point, injection speed, holding pressure, and holding time. This study clarifies the effect of the injection speed, V/P switchover point, and first‐stage holding pressure setting on cavity pressure curves and injection molding quality. These factors were optimized and verified through the injection molding of integrated circuit trays. The experimental results indicate that adjusting the rear speed of filling stage, V/P switchover point, and first‐stage holding pressure, can yield the ideal pressure curve and improve process stability. Compared with the initial process parameter setting, part warpage was reduced by 40% from 0.042 to 0.025 mm, deviation of part width at the end of the filling pattern was reduced by 54% from 0.024 to 0.011 mm, and width range was reduced by 50% from 0.006 to 0.003 mm.
High‐throughput CRISPR‐mediated 3D enrichment platform for functional interrogation of chemotherapeutic resistance
Authors: Grandhi Taraka S. P. , To Jeremy , Romero Angelica , Luna Fabio , Barnes Whitney , Walker John , Moran Rita , Newlin Robbin , Miraglia Loren , Orth Anthony P. , Horman Shane R.
Published: June 2021

Cancer is a disease of somatic mutations. These cellular mutations compete to dominate their microenvironment and dictate the disease outcome. While a therapeutic approach to target‐specific oncogenic driver mutations helps to manage the disease, subsequent molecular evolution of tumor cells threatens to overtake therapeutic progress. There is a need for rapid, high‐throughput, unbiased in vitro discovery screening platforms that capture the native complexities of the tumor and rapidly identify mutations that confer chemotherapeutic drug resistance. Taking the example of the CDK4/6 inhibitor (CDK4/6i) class of drugs, we show that the pooled in vitro CRISPR screening platform enables rapid discovery of drug resistance mutations in a three‐dimensional (3D) setting. Gene‐edited cancer cell clones assembled into an organotypic multicellular tumor spheroid (MCTS), exposed to CDK4/6i caused selection and enrichment of the most drug‐resistant phenotypes, detectable by next‐gen sequencing after a span of 28 days. The platform was sufficiently sensitive to enrich for even a single drug‐resistant cell within a large, drug‐responsive complex 3D tumor spheroid. The genome‐wide 3D CRISPR‐mediated knockout screen (>18,000 genes) identified several genes whose disruptions conferred resistance to CDK4/6i. Furthermore, multiple novel candidate genes were identified as top hits only in the microphysiological 3D enrichment assay platform and not the conventional 2D assays. Taken together, these findings suggest that including phenotypic 3D resistance profiling in decision trees could improve discovery and reconfirmation of drug resistance mechanisms and afford a platform for exploring noncell autonomous interactions, selection pressures, and clonal competition.
Antiplasmodial and Cytotoxic Activities of Extract and Compounds from Ozoroa obovata (Oliv.) R. & A. Fern. var. obovata
Authors: Tajuddeen Nasir , Swart Tarryn , Hoppe Heinrich C. , van Heerden Fanie R.
Published: June 2021

Ozoroa obovata (Oliv.) R. & A. Fern. var. obovata found in KwaZulu‐Natal in South Africa was investigated for phytochemical constituents, and for antiplasmodial and cytotoxic effects. The plant leaves were collected from the University of KwaZulu‐Natal (UKZN) arboretum on the Pietermaritzburg Campus, in March 2019. The inhibitory activity against 3D7 Plasmodium falciparum was determined using the parasite lactate dehydrogenase (pLDH) assay and cytotoxicity against HeLa cells was evaluated using the resazurin assay. The bioactive compounds were isolated by chromatographic purification and their structures were established with spectroscopic and spectrometric techniques. The plant leaf extract displayed significant antiplasmodial activity at 50 μg/mL and was also cytotoxic against HeLa cells. Chromatographic purification of the extract led to the isolation of two biflavonoids, four flavonoid glycosides, a steroid glycoside, and a megastigmene derivative. The compounds displayed antiplasmodial and antiproliferative activities at 50 μg/mL but the activity was substantially reduced at 10 μg/mL. The activities and compounds are being reported in O. obovata for the first time.
Promises and Challenges of Sn‐Based Anodes for Sodium‐Ion Batteries†
Authors: Hu Chenjing , Hou Xiaoxiao , Bai Zhongchao , Yun Longteng , Zhang Xuanrui , Wang Nana , Yang Jian
Published: June 2021

Sn‐based composites are considered as one of the promising anode materials for sodium‐ion batteries (SIBs) due to their high theoretical capacities and suitable operation voltages. However, they suffer the huge volume change and unstable electrolyte/electrode interface during sodiation/desodiation, which causes structure collapse and serious capacity loss. In the past few years, great efforts have been made to ameliorate the performances of Sn by rationally designing electrode structures/components or optimizing electrolyte composition. Here, the underlying sodium‐storage reactions in Sn are summarized based on the results from theoretical calculations and advanced characterizations. Then, the recent progresses of Sn‐based composites, i.e., Sn‐based alloys, Sn/C composites, and Sn oxides/sulfides, with various structures for SIBs are discussed in details. After that, how the electrolyte affects solid‐electrolyte interphase and the electrochemical performances is shown. Finally, the future directions for the applications of Sn‐based composites in SIBs are suggested. Hence, this review provides a comprehensive scenario about the applications of Sn‐based composites in SIBs. It will benefit the future development of alloy‐type anodes in SIBs.
Estimation of design‐based mean squared error of a small area mean model‐based estimator under a nested error linear regression model
Authors: Stefan Marius , Hidiroglou Michael A.
Published: June 2021

In this article, we propose a conditional model estimator (cmmse) for the design‐based mean squared error (dMSE) of a small area mean estimator under the basic unit level model. The mean squared error dMSE refers to the variability of a small area estimator over all possible sample selections. It is different from the model mean squared error (mMSE), traditionally used to measure the efficiency in small area estimation problems. For known model parameters, Rao, Rubin‐Bleuer & Estevao [Rao et al., Survey Methodology 2018; 44, 151–166] showed that dMSE depends on two quadratic finite population parameters. A design estimator of dMSE, denoted as dmse, is obtained by substituting the quadratic parameters with their corresponding design unbiased estimators. Rao, Rubin‐Bleuer & Estevao [Rao et al., Survey Methodology 2018; 44, 151–166] proposed a composite MSE estimator (cmse) based on both the design and the model. This estimator is defined as a weighted average between the design‐based dmse and a model‐based estimator (mmse). Given known variance components, we obtain a new formula for dMSE that accounts for the estimation of the fixed model coefficients. Our conditional model MSE estimator cmmse is obtained by replacing the quadratic finite population parameters by their best predictions under the model, in the new formula of dMSE. Properties of the proposed estimator are studied in terms of design bias, relative root mean squared error, coverage rate and a score function of the confidence intervals.
Measuring force generation within reconstituted microtubule bundle assemblies using optical tweezers
Authors: Al Azzam Omayma , Trussell Cameron Lee , Reinemann Dana N.
Published: June 2021

Kinesins and microtubule associated proteins (MAPs) are critical to sustain life, facilitating cargo transport, cell division, and motility. To interrogate the mechanistic underpinnings of their function, these microtubule‐based motors and proteins have been studied extensively at the single molecule level. However, a long‐standing issue in the single molecule biophysics field has been how to investigate motors and associated proteins within a physiologically relevant environment in vitro. While the one motor/one filament orientation of a traditional optical trapping assay has revolutionized our knowledge of motor protein mechanics, this reductionist geometry does not reflect the structural hierarchy in which many motors work within the cellular environment. Here, we review approaches that combine the precision of optical tweezers with reconstituted ensemble systems of microtubules, MAPs, and kinesins to understand how each of these unique elements work together to perform large scale cellular tasks, such as but not limited to building the mitotic spindle. Not only did these studies develop novel techniques for investigating motor proteins in vitro, but they also illuminate ensemble filament and motor synergy that helps bridge the mechanistic knowledge gap between previous single molecule and cell level studies.
Public–private collaboration in the provision of palliative care for children and adolescents with cancer: A Chilean experience
Authors: Fernández Jazmine , Roje Dunja , Rossell Nuria , Zubieta Marcela
Published: June 2021

Background

In Chile, children and adolescents with cancer in need of palliative care receive services through a collaborative scheme run in coordination between the hospitals of the public health system that attend children with cancer and the non‐profit civil society organization Fundación Nuestros Hijos (FNH).

Aim

The main objective of this article is to offer a summary of the Chilean experience in the provision of palliative care services for children and adolescents with cancer, as an example of a public‐private partnership that improves the quality of life and the end‐of‐life experience for the children, adolescents, and their families.

Methods and results

The palliative care program works with the children and their families as main members of the team, providing medical services for pain and symptom alleviation, psycho‐social support, rehabilitation for the improvement of quality of life, and aid to secure the best physical conditions for the child at home or in temporary housing for the whole family.

Conclusion

The private‐public collaboration between the Chilean health system and the FNH is a successful model to help families suffering the devastating loss of a child.
Quantitative modelling of fish habitat in a large regulated river in a changing climate
Authors: Wegscheider Bernhard , Linnansaari Tommi , Monk Wendy A. , Ndong Mouhamed , Haralampides Katy , St‐Hilaire Andre , Schneider Matthias , Curry R. Allen
Published: June 2021

The expansion of hydropower in combination with the already existing infrastructure and a changing climate are significantly influencing the world's rivers. The resulting alteration in flow regimes is expected to strongly affect fish habitat and associated fish communities both spatially and temporally. Using habitat modelling, this study identified habitat bottlenecks during the critical summer low flow period and fish assemblages that will be most susceptible to regulated and predicted future flow regimes in the Saint John River downstream the Mactaquac Generating Station. Expert knowledge‐based habitat models were applied at the meso‐scale to evaluate the influence of alternative future flow regimes on habitat suitability indices of fish assemblages. Dam renewal and removal scenarios predicted low habitat suitability for rheophilic fish species, particularly during prolonged low flow periods in dry years. Limnophilic and eurytopic fish assemblages were not expected to be limited in habitat conditions. Overall, the proposed modelling approach represents a promising tool to support the development of environmental flows in large regulated rivers that face challenges with ageing infrastructure and a changing climate.
Oxidative Degradation of Azo Dyes in Aqueous Solution by Water‐Soluble Iron Porphyrin Catalyst
Authors: Saha Tapan Kumar , Frauendorf Holm , Meyer Franc
Published: June 2021

Textile and food industries produce a significant volume of effluents containing azo dyes and other pollutants. These effluents are serious environmental threats, and new methods for their treatment and for the degradation of azo dyes are thus attracting much attention. The current study deals with the oxidative degradation of azo dyes by meso‐tetrakis(1‐methylpyridinium‐4‐yl)prophyrinatoiron(III), [FeIII(tmpyp)], and meta‐chloroperoxy benzoic acid (m‐CPBA) in aqueous solution at room temperature. The catalytic degradation of azo dyes was investigated by using rapid‐scan stopped‐flow spectrophotometry as a function of solution pH, [catalyst], [m‐CPBA], [dye] and [surfactants]. To obtain mechanistic insight, the reaction between [FeIII(tmpyp)] and m‐CPBA was also studied in aqueous solution in absence of azo dyes. Spectral analyses and kinetic data show that [FeIII(tmpyp)] is transformed into the transient intermediate [FeIV(O)(tmpyp)].+ (a compound I analog) within 20–30 ms followed by the formation of relatively stable [FeIV(O)(tmpyp)] (a compound II analog). Batch experiments reveal that the dye degradation rate is influenced by the solution pH and the concentrations of [FeIII(tmpyp)], m‐CPBA, dye, and surfactants. On the basis of the kinetic and spectroscopic data, a mechanistic scheme for the dye degradation reaction and a steady‐state rate equation are proposed. The products resulting from oxidative degradation of the azo dye amaranth have been analyzed by HPLC‐UV‐HRMS.
Nitric Oxide Release for Enhanced Biocompatibility and Analytical Performance of Implantable Electrochemical Sensors
Authors: Zhang Qi , Meyerhoff Mark E.
Published: June 2021

The real‐time, continuous monitoring of glucose/lactate, blood gases and electrolytes by implantable electrochemical sensors holds significant value for critically ill and diabetic patients. However, the wide‐spread use of such devices has been seriously hampered by implant‐initiated host responses (e. g., thrombus formation, inflammatory responses and bacterial infection) when sensors are implanted in blood or tissue. As a result, the accuracy and usable lifetime of in vivo sensors are often compromised. Nitric oxide (NO) is an endogenous gas molecule able to inhibit platelet adhesion/activation, inflammatory responses and bacterial growth. As such, the release of NO from the surfaces of in vivo sensors is a promising strategy for enhancement of their biocompatibility and analytical performance. In this review, the physiological functions of NO to improve the biocompatibility of implantable electrochemical sensors are introduced, followed by a brief analysis of chemical approaches to realize NO release from such devices. A detailed summary of the various types of NO releasing electrochemical sensors reported to date and their performance in benchtop and/or in vivo testing are also provided. Finally, the prospects of future developments to further advance NO releasing sensor technology for clinical use are discussed.
Development of low‐cost planar electrodes and microfluidic channels for applications in capacitively coupled contactless conductivity detection (C4D)
Authors: Takekawa Victor Sadanory , Marques Letícia Aparecida , Strubinger Ethan , Segato Thiago Pinotti , Bogusz Stanislau , Brazaca Laís Canniatti , Carrilho Emanuel
Published: June 2021

Electrochemical techniques are commonly applied to micro total analysis system (μTAS) devices mainly due to its high sensitivity and miniaturization capacity. Among many electrochemical techniques, capacitively coupled contactless conductivity detection (C4D) stands out for not requiring direct electrode‐solution contact, avoiding several problems such as electrolysis, bubble formation, and metal degradation. Furthermore, the instrumentation required for C4D measurements is compact, low cost, and easy to use, allowing in situ measurements to be performed even by nonspecialized personal. Contrarily, the production of metallic electrodes and microchannels adequate for C4D measurements commonly requires specialized facilities and workers, increasing the costs of applying these methods. We propose alternatives to batch manufacture metallic electrodes and polymeric microchannels for C4D analysis using more straightforward equipment and lower‐cost materials. Three devices with different dielectric layer compositions and electrode sizes were tested and compared regarding their analytical performance. The constructed platforms have shown a reduction of more than 64% in cost when compared to traditional techniques and displayed good linearity (R2 ≥ 0.994), reproducibility (RSD ≤ 4.07%, n = 3), and limits of detection (≤0.26 mmol/L) when measuring standard NaCl samples. Therefore, the proposed methods were successfully validated and are available for further C4D applications such as diagnosis of dry‐eye syndrome.
Testing and estimation of X‐chromosome SNP effects: Impact of model assumptions
Authors: Song Yilin , Biernacka Joanna M. , Winham Stacey J.
Published: June 2021

Interest in analyzing X chromosome single nucleotide polymorphisms (SNPs) is growing and several approaches have been proposed. Prior studies have compared power of different approaches, but bias and interpretation of coefficients have received less attention. We performed simulations to demonstrate the impact of X chromosome model assumptions on effect estimates. We investigated the coefficient biases of SNP and sex effects with commonly used models for X chromosome SNPs, including models with and without assumptions of X chromosome inactivation (XCI), and with and without SNP–sex interaction terms. Sex and SNP coefficient biases were observed when assumptions made about XCI and sex differences in SNP effect in the analysis model were inconsistent with the data‐generating model. However, including a SNP–sex interaction term often eliminated these biases. To illustrate these findings, estimates under different genetic model assumptions are compared and interpreted in a real data example. Models to analyze X chromosome SNPs make assumptions beyond those made in autosomal variant analysis. Assumptions made about X chromosome SNP effects should be stated clearly when reporting and interpreting X chromosome associations. Fitting models with SNP × Sex interaction terms can avoid reliance on assumptions, eliminating coefficient bias even in the absence of sex differences in SNP effect.
Colonic perforation due to ovarian cancer invasion: An unusual event
Authors: Pitarch‐Martínez María , Blanco‐Elena Juan Antonio , Robles‐Quesada María Teresa , Alberca‐Páramo Ana , Granados‐García José
Published: June 2021

Synopsis

The present study reports a case of colonic perforation, which is a rare presentation of ovarian cancer that requires emergent surgical treatment.
In vivo evidence for the cellular basis of central hypoventilation of Rett syndrome and pharmacological correction in the rat model
Authors: Wu Yang , Cui Ningren , Xing Hao , Zhong Weiwei , Arrowood Colin , Johnson Christopher M. , Jiang Chun
Published: June 2021

Rett syndrome (RTT) is a neurodevelopmental disorder caused mostly by mutations in the MECP2 gene. RTT patients show periodical hypoventilation attacks. The breathing disorder contributing to the high incidence of sudden death is thought to be due to depressed central inspiratory (I) activity via unknown cellular processes. Demonstration of such processes may lead to targets for pharmacological control of the RTT‐type hypoventilation. We performed in vivo recordings from medullary respiratory neurons on the RTT rat model. To our surprise, both I and expiratory (E) neurons in the ventral respiratory column (VRC) increased their firing activity in Mecp2‐null rats with severe hypoventilation. These I neurons including E–I phase‐spanning and other I neurons remained active during apneas. Consistent with enhanced central I drive, ectopic phrenic discharges during expiration as well as apnea were observed in the Mecp2‐null rats. Considering the increased I neuronal firing and ectopic phrenic activity, the RTT‐type hypoventilation does not seem to be caused by depression in central I activity, neither reduced medullary I premotor output. This as well as excessive E neuronal firing as shown in our previous studies suggests inadequate synaptic inhibition for phase transition. We found that the abnormal respiratory neuronal firing, ectopic phrenic discharge as well as RTT‐type hypoventilation all can be corrected by enhancing GABAergic inhibition. More strikingly, Mecp2‐null rats reaching humane endpoints with severe hypoventilation can be rescued by GABAergic augmentation. Thus, defective GABAergic inhibition among respiratory neurons is likely to play a role in the RTT‐type hypoventilation, which can be effectively controlled with pharmacological agents.
Bird flu outbreak amidst COVID‐19 pandemic in South Africa: Efforts and challenges at hand
Authors: Uwishema Olivier , Adriano Lubanga F. , Chalhoub Elie , Onyeaka Helen , Mhanna Melissa , David Success C. , Nasrallah Yves , Ribeiro Lucas L. P. A. , Berjaoui Christin
Published: June 2021

Over the months of April and May 2021, South Africa has witnessed several outbreaks of highly infective avian influenza (H5N1) in different poultry farms. This came as a shock to a country that was already battling with the deadly COVID‐19 pandemic. The emergence of the virus has spurred import bans and massive culls in the poultry business. Local experts have also called for a restriction on the movement of people and cars in and out of their chicken farms. Employees have also been encouraged to shower in the mornings when they arrive at the farms and wear fresh clothes, as the flu spreads very quickly. In a country that is already facing the economic implications of the COVID‐19, this has the potential to cause a significant dent in the economy, as well as severely impact people's day‐to‐day life. Bird flu—also called avian influenza—is a viral infection that can infect not only birds but also humans and other animals. The threat of a new influenza pandemic has prompted countries to draft national strategic preparedness plans to prevent, contain and mitigate the next human influenza pandemic. This paper describes the South African burden, current efforts, and preparedness against the avian influenza virus.
A novel method for ranking CMIP6 global climate models over the southeast Asian region
Authors: Desmet Quentin , Ngo‐Duc Thanh
Published: June 2021

The performance of 28 CMIP6 models in simulating the Southeast Asian (SEA) climate is investigated. An evaluation methodology is developed to evaluate spatiotemporal patterns of precipitation, near‐surface temperature, and 850‐hPa wind. Mean annual cycles of temperature and rainfall are assessed separately over Indochina, the Maritime Continent, and the Philippines; and the summer and winter seasons are selected for studying spatial patterns. Within these distinctions, statistics comparing the models to reference data are calculated. The patterns' shape and phase are notably studied, and wind direction differences are assessed specifically over the most major wind flows. We present a scoring procedure allowing us to give each model a unique score reporting on the diverse evaluation aspects, hence establishing a ranking. The process rests on a scoring function growing exponentially with the performance: it favours the models combining good performances according to the largest number of criteria. The assessment highlights EC‐Earth3 and EC‐Earth3‐Veg, which conduct excellent simulations of the regional patterns of rainfall and wind. Their temperature outputs are also reliable, but CNRM‐CM6 ranks first for this variable, while finishing third globally. Local differences are discussed: we emphasize, among other things, the diverse impact of topography on temperature and rainfall, or the frequent deviation of winter winds circulating from the South China Sea to the Java Sea. In addition, a similarity study reveals major difficulties for simulating near‐equatorial annual cycles of temperature and precipitation whereas the summer monsoon spatial rainfall patterns bring out the largest discrepancies. In any event, the top models pointed out by our ranking constitute a high‐performance subset that further climate modelling experiments in SEA can rely on.
Untargeted metabolomics analysis identifies creatine, myo‐inositol, and lipid pathway modulation in a murine model of tendinopathy
Authors: Sikes Katie J. , McConnell Anna , Serkova Natalie , Cole Brian , Frisbie David
Published: June 2021

Tendinopathy has been broadly characterized as alterations in cell proliferation, extracellular matrix turnover/synthesis, and inflammatory alterations. However, the underlying glucose metabolism pathways which contribute to these responses have not been well explored. The potential link between glucose metabolism and tendon pathology is interesting from a global standpoint since the development of spontaneous tendinopathy is associated with systemic metabolic disorders including diabetes mellitus. Therefore, the overarching goal of this study was to understand the potential pathogenic role of glucose metabolism‐driven mechanisms in the development of tendinopathy. To test this, we have utilized an untargeted metabolomics approach to discover pathways which may be altered following tendinopathic injury and treadmill running in an established murine model of TGF‐β1 induced tendinopathy. While specific tendon glucose alterations were not observed via metabolomics or 18F‐fluoroeoxyglucose (FDG) positron emission tomography/microcomputed tomography imaging (18F‐FDG PET/CT), metabolites including creatinine, D‐chiro‐inositol, and lipids were dysregulated following tendon injury. As novel pathways for manipulation, the creatine pathway, myo‐inositol pathway, and lipid signaling may lead to the development of enhanced preventative strategies and therapeutic options for all patients who suffer from tendon‐related injuries.
Vein preservation strategies to improve the survival rate of the infrahyoid musculocutaneous flap
Authors: Nguyen Khoi Anh , Ngo Tham Xuan , Nguyen Can Quoc , Wein Richard O.
Published: June 2021

The infrahyoid musculocutaneous flap (IHMCF) is a good alternative in the reconstruction of moderate‐sized oral cavity surgical defects. Insufficient venous drainage can significantly affect the survival rate of this flap.

Objectives

Identify the survival rates of the IHMCF and evaluate the functional capacity of reconstructed patients.

Design

We report a case series.

Setting

This study took place at the Department of Head and Neck Surgery of Oncology Hospital Ho Chi Minh City, the largest oncology center in South Vietnam.

Participants

One hundred and twelve patients with surgical defects after oral cavity resection for cancer underwent IHMCF reconstruction from November 2013 to November 2018. During the harvest of the flap, our modification of the surgical technique specifically attempted to preserve more secondary veins for IHMCF.

Main Outcome Measures

Postoperative viability of the flap was checked by clinical observation. The last examination was performed at 3‐months after reconstructive operation or after the completion of adjuvant radiotherapy. The functional capacity of our patients was evaluated by three physicians (Head and Neck Surgeon, Radiation Oncologist, and Physiatrist) with understandability of speech scale and the functional oral intake score items assessed.

Results

Two cases of partial skin necrosis (1.8%) were experienced. The majority of patients demonstrated favorable functional rehabilitation at long‐term follow up.

Conclusions

The IHMCF is a reliable flap suitable for moderate‐sized defects of the oral cavity. Altering the surgical approach to specifically preserve more venous outflow can improve the survival rate of the flap.

Level of Evidence

4.
Reliability and construct validity of the Duchenne Video Assessment
Authors: Contesse Marielle G. , Sapp Amber T. L. , Apkon Susan D. , Lowes Linda P. , Dalle Pazze Laura , Leffler Mindy G.
Published: June 2021

Introduction

The Duchenne Video Assessment (DVA) assesses quality of movement as an indication of Duchenne muscular dystrophy (DMD) disease severity. Caregivers video record patients performing home‐based movement tasks using a mobile application, and physical therapists (PTs) rate the videos using scorecards with prespecified compensatory movement criteria. Reliability and construct validity of the DVA were tested using video and Pediatric Outcomes Data Collection Instrument (PODCI) data from patients with DMD and healthy controls from a separate study.

Methods

Fifteen PTs were trained and certified as DVA raters. All raters scored videos of five subjects performing each movement task; nine raters rescored the same videos four weeks later. Three raters scored videos from an average of 25 subjects for each movement task. Aggregate scores were used to test construct validity. An expert DMD clinician assigned each video to a severity group for known‐groups analyses. Differences between rater scores across severity groups were tested and correlations between DVA and PODCI scores were calculated.

Results

Inter‐rater reliability (intraclass correlation coefficient [ICC]) between all 15 raters ranged from 0.70 to 0.97 for all movement tasks. Mean intra‐rater reliability ICC for nine raters ranged from 0.82 to 0.98 for all movement tasks. There were statistically significant differences between known severity groups for all movement tasks. The DVA correlated strongly with related PODCI constructs of physical function and weakly with unrelated constructs.

Discussion

The DVA was found to be a reliable and valid tool for measuring quality of movement as an indication of disease severity.
Evaluation of the 24‐h pad weight test as continence rate assessment tool after artificial urinary sphincter implantation for postprostatectomy urinary incontinence: A Swedish retrospective cohort study
Authors: Reus Christine , Brattås Izabelle , Volz Daniela , Sydén Filip , Grufman Katarina Hallén , Mozer Pierre , Renström‐Koskela Lotta
Published: June 2021

Aim

Patient‐reported pad‐count as continence rate assessment tool after artificial urinary sphincter (AUS) implantation is common. However, lack of standardized continence definition using this method results in heterogeneous published efficacy outcomes. Data on 24‐h pad weight tests (PWT) after primary AUS implantation for postprostatectomy urinary incontinence (PPUI) is scarce.

Our aim was to evaluate the 24‐h PWT as an efficacy assessment tool and correlate it to qualitative outcomes using validated questionnaires.

Methods

This retrospective, single center, follow‐up cohort study, evaluated 180 patients who underwent primary AUS implantation for PPUI from 2005 to 2018. Voiding diaries, 24‐h PWT, validated patient satisfaction and quality of life (QoL) questionnaires were collected pre‐operatively and at 3–6 months postactivation, using the institution's Electronic Medical Records.

Results

The median preoperative and postoperative 24‐h PWT values were 494 (interquartile range [IQR]: 304–780) and 7 (IQR: 0–25) g respectively with a significant improvement in urinary leakage of 489.5 g 99.1% (p < 0.001). Median preoperative and postoperative I‐QoL results increased from 33.5 (IQR: 19.3–63.6) to 86.4 (IQR: 73.9–94.3) points, with a significant 52.9 points improvement in QoL (p < 0.001). Similarly, the median preoperative and postoperative ICIQ‐SF values decreased from 20 (IQR: 17–21) to 5 (IQR: 3–9) points, showing a significant improvement of 15 points (p < 0.001). We also found a significant correlation between PWT and patient satisfaction.

Conclusion

The 24‐h PWT provides a reliable and objective assessment of continence rates, with a strong correlation to qualitative outcomes, after primary AUS implantation for PPUI. Its use could help reduce reported outcome heterogeneity across studies.
Multidisciplinary Care ofBRAF-MutantStageIIIMelanoma: A Physicians Perspective Review
Authors: Cornelius Lynn A. , Fields Ryan C. , Tarhini Ahmad
Published: June 2021

Prognosis among patients with stage III melanoma can vary widely depending on the risk of disease relapse. Therefore, it is vital to optimize patient care through accurate diagnosis and staging as well as thoughtful treatment planning. A multidisciplinary team (MDT) approach, which involves active collaboration among physician specialists across a patient's disease journey, has been increasingly adopted as the standard of care for treatment of a variety of cancers, including melanoma. This review provides an overview of MDT care principles for patients with BRAF-mutant–positive, stage III cutaneous melanoma and summarizes current literature, clinical experiences, and institutional best practices. Therapeutic goals from dermatologic, surgical, and medical oncologist perspectives regarding MDT care throughout a patient's disease course are discussed. Additionally, the role of each specialty's involvement in testing for predictive biomarkers at relevant time points to facilitate informed treatment decisions is discussed. Last, instances of successful MDT treatment of other cancers and key lessons to optimize MDT patient care in cutaneous melanoma are provided. Several aspects of MDT patient care are considered vital, such as the importance of staging via pathological examination and imaging, biomarker testing, and interdisciplinary physician and patient engagement throughout the course of treatment. Use of MDTs has the potential to improve patient care in cutaneous melanoma by improving the speed and accuracy of diagnosis, implementing a personalized treatment plan early on, and being proactive in adverse event management. Physician perspectives described in this review may lead to better outcomes, quality of life, and overall patient satisfaction.

Implications for Practice

As more cancer therapies emerge, it is critical to optimize patient care and treatment planning. The multidisciplinary team (MDT) approach, which involves active collaboration among specialists, has led to encouraging survival results in multiple cancer types. As MDT care becomes more widely adopted in the treatment of melanoma, accurate diagnosis and staging are important, as clinical outcomes for stage III disease vary widely by substage. Because ~50% of melanomas harbor BRAF mutations, testing is important for an informed treatment decision. Interdisciplinary physician-patient engagement throughout the course of treatment can improve comorbidity and adverse event management to optimize patients' treatment journeys.
Using social media to understand adults’ experiences of physical activity as a child living with type 1 diabetes
Authors: Morrow Diane , Lennon Marilyn , Kirk Alison , Muirhead Fiona
Published: June 2021

Challenges exist in facilitating engagement with physical activity for adolescents living with type 1 diabetes. These are known to include both physical and psychosocial barriers. Exploring retrospective reflections of lived experiences of adults growing up with diabetes may provide meaningful insights into these challenges, to help inform future interventions that aim to increase physical activity in adolescents living today with type 1 diabetes (T1D).

The aim of this study was to understand adults’ experiences of physical activity as a child living with T1D.

Social media were used (Twitter and Facebook) to allow adults to share their experiences of engaging in physical activity as a child with T1D. The digital stories (posts) were then thematically analysed to understand underlying factors affecting engagement (both positively and negatively) with physical activity as a child living with diabetes.

A total of 42 individual participants took part, providing 68 posts (44 replies from Twitter, 24 from Facebook). The six key themes generated as contributing factors that affected engagement with physical activity as a child living with T1D were: (1) Acceptance; (2) Education and knowledge; (3) Support; (4) Coping behaviours; (5) Identity; and (6) Perceptions of control.

Our childhood experiences may influence later behaviours as an adult. It is important to understand what factors adults identify retrospectively as influencing their engagement with physical activity as a child. Using social media to capture childhood experiences enabled the identification of six key themes for consideration in the design of interventions to support physical activity in adolescents living with T1D. Copyright © 2021 John Wiley & Sons.
A critical assessment of factors influencing the perceived professional benefit of internet nurses
Authors: Li Xiaoxu , Zhu Yichang , Yang Bo , Wu Bing , Wang Meixiang , Zhao Yun
Published: June 2021

Objective

We investigated the perceived professional benefit of nurses engaged in internet nursing services of Internet Cooperative Hospitals in Nanjing, China, and explored factors influencing nurse assessment.

Method

From July to August 2020, 300 nurses engaged in internet nursing services at the Internet Cooperative Hospitals of Nanjing, China were assessed using a standardized general information questionnaire with a cumulative score of 145 (range 29‐145).

Result

The perceived professional benefit score measured in this study was 121.21 ± 14.97. Linear regression analysis showed that personal recognition of internet nursing services, children's education, position, leader's attitude toward nurses engaging in internet nursing services, and the number of night shifts were the main factors influencing score.

Conclusion

This study demonstrated that perceived professional benefit was influenced by diverse factors. We recommend that targeted intervention measures be used to ensure that nursing managers provide opportunities and platforms for nurses who actively participate in online nursing services.
Epidemiology, prognosis and management of potassium disorders in Covid‐19
Authors: Noori Maryam , Nejadghaderi Seyed A. , Sullman Mark J. M. , Carson‐Chahhoud Kristin , Kolahi Ali‐Asghar , Safiri Saeid
Published: June 2021

Coronavirus disease (Covid‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), is currently the largest health crisis facing most countries. Several factors have been linked with a poor prognosis for this disease, including demographic factors, pre‐existing comorbidities and laboratory parameters such as white blood cell count, D‐dimer, C‐reactive protein, albumin, lactate dehydrogenase, creatinine and electrolytes. Electrolyte abnormalities particularly potassium disorders are common among Covid‐19 patients. Based on our pooled analysis, hypokalemia and hyperkalemia occur in 24.3% and 4.15% of Covid‐19 patients, respectively. Potassium level deviation from the normal range may increase the chances of unfavorable outcomes and even death. Therefore, this article reviewed the epidemiology of potassium disorders and explained how hypokalemia and hyperkalemia are capable of deteriorating cardiac outcomes and the prognosis of Covid‐19 for infected patients. The article finishes by highlighting some important considerations in the management of hypokalemia and hyperkalemia in these patients.
Hepatic vein tumor thrombosis in patients with hepatocellular carcinoma: Prevalence and clinical significance
Authors: Mähringer‐Kunz Aline , Meyer Franziska I. , Hahn Felix , Müller Lukas , Düber Christoph , Pinto Dos Santos Daniel , Galle Peter R. , Weinmann Arndt , Kloeckner Roman , Schotten Sebastian
Published: June 2021

Background

There is strong evidence that portal vein tumor thrombosis (PVTT) is associated with poor survival in patients with hepatocellular carcinoma (HCC). However, data regarding the clinical significance of hepatic vein tumor thrombosis (HVTT) is rare, particularly in Western patients.

Objective

To determine the HVTT prevalence in a Western patient population and its impact on survival.

Methods

We included 1310 patients with HCC treated in our tertiary referral center between January 2005 and December 2016. HVTT and PVTT were diagnosed with contrast‐enhanced cross‐sectional imaging. Overall survival (OS) was calculated starting from the initial HCC diagnosis, and in a second step, starting from the first appearance of vascular invasion.

Results

We observed macrovascular invasion (MVI) in 519 patients who suffered from either isolated HVTT (n = 40), isolated PVTT (n = 352), or both combined (HVTT + PVTT) (n = 127). Calculated from the initial HCC diagnosis, the median OS for patients with isolated HVTT was significantly shorter than that of patients without MVI (13.3 vs. 32.5 months, p < 0.001). Calculated from the first appearance of MVI, the median OS was similar among patients with isolated HVTT (6.5 months), isolated PVTT (5 months), and HVTT + PVTT (5 months). Multivariate analysis confirmed HVTT as an independent risk factor for poor survival.

Conclusions

HVTT may be more common than typically reported. In most patients, it was accompanied by PVTT. Isolated HVTT occurred less frequently and later than isolated PVTT; however, once developed, it had the same deleterious impact on survival. Therefore, patients with HVTT should be classified as advanced stage of HCC.
“I have Learned Non-Euclidean Geometry Just from this Book” - Some facets of the correspondence between Friedrich Engel and David Hilbert
Authors: Ullrich Peter
Published: June 2021

Friedrich Engel and David Hilbert learned to know each other at Leipzig in 1885 and exchanged letters in particular during the next 15 years which contain interesting information on the academic life of mathematicians at the end of the 19th century. In the present article we will mainly discuss a statement by Hilbert himself on Moritz Pasch’s influence on his views of geometry, and on personnel politics concerning Hermann Minkowski and Eduard Study but also Engel himself.
A 15-min non-competitive homogeneous assay for microcystin and nodularin based on time-resolved Förster resonance energy transfer (TR-FRET)
Authors: Akter Sultana , Lamminmäki Urpo
Published: June 2021

Simple and rapid methods are required for screening and analysis of water samples to detect cyanobacterial cyclic peptide hepatotoxins: microcystin/nodularin. Previously, we reported a highly sensitive non-competitive heterogeneous assay for microcystin/nodularin utilizing a generic anti-immunocomplex (anti-IC) single-chain fragment of antibody variable domains (scFv) isolated from a synthetic antibody library together with a generic adda ((2S,3S,4E,6E,8S,9S)-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4,6-dienoic acid)-specific monoclonal antibody (Mab) recognizing the common adda part of the microcystin/nodularin. Using the same antibody pair, here we report a homogeneous non-competitive assay for microcystin/nodularin based on TR-FRET (time-resolved Förster resonance energy transfer) measurement. The anti-IC scFv labeled with Alexa Fluor 680 and the Mab labeled with europium enabled the FRET process to occur in the presence of microcystin/nodularin. The TR-FRET signal is proportional to the toxin concentration in the sample. The rapid (15 min) homogeneous assay without requiring any washing step detected all the tested nine toxin variants (microcystin-LR, -dmLR, -RR, -dmRR, -YR, -LY, -LF -LW, and nodularin-R). Very good signal to blank ratio (~13) was achieved using microcystin-LR and the sample detection limit (blank+3SD of blank) for microcystin-LR was ~0.3 μg/L (~0.08 μg/L in 80-μL reaction well). The practical application of the TR-FRET assay was demonstrated with water samples spiked with microcystin-LR as well as with environmental water. The average recoveries of microcystin-LR from spiked water ranged from 65 to 123%. Good correlation (r2 = 0.73 to 0.99) with other methods (liquid chromatography-mass spectrometry and previously reported heterogeneous assay) was found when environmental samples were analyzed. The developed wash-free assay has the potential to play as a quick screening tool to detect microcystin/nodularin from water below the World Health Organization’s guideline limit (1 μg/L of microcystin-LR).

Graphical abstract
Fracture Incidence and the Relevance of Dietary and Lifestyle Factors Differ in the United Kingdom and Hong Kong: An International Comparison of Longitudinal Cohort Study Data
Authors: Hayhoe Richard P. G. , Chan Ruth , Skinner Jane , Leung Jason , Jennings Amy , Khaw Kay-Tee , Woo Jean , Welch Ailsa A.
Published: June 2021

Geographic variation in fracture risk may be due to divergent profiles of dietary, lifestyle, and other risk factors between populations. We investigated differences in fracture rates between two older-population cohorts: the European Prospective Investigation into Cancer and Nutrition (EPIC) Norfolk cohort (n = 7732) in the United Kingdom (UK), and the Mr and Ms Os cohort (n = 3956) in Hong Kong (HK). Data were collected by questionnaires, laboratory assessments, and hospital records. Incidence of hip, spine, and wrist fractures in the two cohorts was calculated and multivariable regression was used to explore variables important to fracture risk. Total hip, spine, and wrist fracture incidence was higher in the UK vs HK for women (13.70 vs 8.76 per 1000 person-years; p < 0.001), but not men (5.95 vs 5.37 per 1000 person-years; p = 0.337), and the proportions of different fractures also varied between cohorts (p < 0.001). Hip fracture was the most common UK fracture (accounting for 56.8% fractures in men and 52.6% in women), while wrist fracture was most common in HK (42.9% in men and 57.9% in women). The major contributor to total fracture risk in multivariable regression models of both cohorts and sexes, was age; with BMI also an important contributor to fracture risk HK men and UK women. The distribution of factors relevant to fracture risk, and the rates of different fractures, varied significantly between UK and HK cohorts. However, the importance of each factor in contributing to fracture risk was similar between the cohorts. The differences in fracture rates suggest targeted approaches may be required when developing interventions and public health recommendations to reduce the burden of osteoporosis in these two countries.