bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of a novel heterozygous mutation in the MITF gene in an Iranian family with Waardenburg syndrome type II using next‐generation sequencing
Authors: Nasirshalal Mahzad , Panahi Mohammad , Javanshir Nahid , Salmani Hamzeh
Published: May 2021

Background

Waardenburg syndrome (WS) is a genetically heterogeneous syndrome with both autosomal recessive and dominant inheritance. WS causes skin and iris pigmentation accumulation and sensorineural hearing loss, in varying degrees. There are four WS types with different characteristics. WS1 and WS2 are the most common and have a dominant inheritance. WS2 is caused by mutations in the microphthalmia‐associated transcription factor (MITF) gene.

Methods

An Iranian couple with hearing loss was recruited in the present study. First, they were screened for GJB2 and GJB6 gene mutations, and then whole‐exome sequencing 100X was performed along with bioinformatics analysis.

Results

A novel pathogenic heterozygous mutation, c.425T>A; p.L142Ter, was detected in the MITF gene's exon 4. Bioinformatics analysis predicted c.425T>A; p.L142Ter as a possible pathogenic variation. It appears that the mutated transcript level declines through nonsense‐mediated decay. It probably created a significantly truncated protein and lost conserved and functional domains like basic helix‐loop‐helix‐zipper proteins. Besides, the variant was utterly co‐segregated with the disease within the family.

Conclusions

We investigated an Iranian family with congenital hearing loss and identified a novel pathogenic variant c.425T>A; p. L142Ter in the MITF gene related to WS2. This variant is a nonsense mutation, probably leading to a premature stop codon. Our data may be beneficial in upgrading gene mutation databases and identifying WS2 causes.
Performance of HIV detection in Zhejiang province in China: The Pareto principle at work
Authors: Zhang Jiafeng , Ding Xiaobei , Zhou Xin , Chen Wanjun , Yao Jiaming , Guo Zhihong , Chen Lin , Xia Yan , Fan Qin
Published: May 2021

Background

Timely detection of HIV infection is critical for curbing the AIDS epidemic, and building an extensive and effective HIV laboratory network is of great importance. Therefore, improving quality management of the laboratory network and optimizing detection strategies are desirable research issues.

Methods

We assessed the applicability of the Pareto principle to HIV detection performance. We conducted a retrospective review of basic information and numbers of screening tests among an HIV laboratory network (1,452 laboratories) in Zhejiang province in 2014 and statistically analyzed HIV testing data for different population categories.

Results

Approximately, 80% of the cumulative HIV screening tests and positive screening tests originated from 17.3% (251/1,452) and 11.7% (170/1,452) of the laboratories in the whole province, respectively, and similar patterns were observed at the prefectural level. We found that the top five population screening categories (25%, 5/20) had the highest contribution (approximately 80%) to not only the number of screening tests (77.2%) but also the numbers of positive (76.4%) and confirmed positive tests (81.5%).

Conclusions

The Pareto principle provides a method for identifying noteworthy laboratories to deliver prior quality supervision and developing highly efficient screening strategies that best suit local needs.
Application of Physiologically Based Pharmacokinetic‐Pharmacodynamic Modeling in Preterm Neonates to Guide Gentamicin Dosing Decisions and Predict Antibacterial Effect
Authors: Neeli Harshith , Hanna Nazeeh , Abduljalil Khaled , Cusumano Jaclyn , Taft David R.
Published: May 2021

Clinical studies in preterm neonates are rarely performed due to ethical concerns and difficulties associated with trials and recruitment. Consequently, dose selection in this population is primarily empirical. Scaling neonatal doses from adult doses does not account for developmental changes and may not accurately predict drug kinetics. This is especially important for gentamicin, a narrow therapeutic index aminoglycoside antibiotic. While gentamicin's bactericidal effect is associated with its peak plasma concentration, keeping trough concentrations below 1 µg/mL prevents toxicity and also helps to counteract adaptive resistance in bacteria such as Escherichia coli. In this study, physiologically based pharmacokinetic‐pharmacodynamic (PBPK‐PD) modeling was used to support and/or guide dosing decisions and to predict the antibacterial effect in preterm neonates. A gentamicin PBPK model was successfully verified in healthy adults and preterm neonates across all gestational ages. Clinical data from a neonatal intensive care unit at NYU Langone Hospital–Long Island was used to identify dosing regimens associated with increased incidence of elevated gentamicin trough concentrations in different preterm patient cohorts. Model predictions demonstrated that a higher dose with an extended‐dosing interval (every 36 hours) in neonates with a postmenstrual age of 30 to 34 weeks and ≥35 weeks, with postnatal age 8 to 28 days and 0 to 7 days, respectively, were more likely to have a trough <1 µg/mL when compared with once‐daily (every 24 hours) dosing. PBPK‐PD modeling suggested that a higher dose administered every 36 hours may provide effective antibacterial therapy.
Using learning management software data to compare students' actual and self‐reported viewing of video lectures
Authors: Scott JoAnna M. , Bohaty Brenda S. , Gadbury‐Amyot Cynthia C.
Published: May 2021

Purpose

Student engagement is typically measured by class attendance and questionnaires. Learning management systems (LMS) provide additional sources of objective data that can evaluate student performance. This study compared dental students’ self‐report of course video viewing with LMS data.

Methods

Dental students in a 2018 flipped pediatric dentistry course were given a questionnaire after course completion that captured self‐reported course video viewing. Student data and time spent on videos were extracted from the LMS and matched to the questionnaire. McNemar's test evaluated differences between self‐reported and matching LMS data.

Results

Of the 109 enrolled students, 99 (91%) completed the questionnaire. Most students self‐reported that they watched more than half of the videos (71%), re‐watched at least once (89%), and watched at times other than 8 a.m.–5 p.m. (80%). Of the 104 students with data from the LMS, 40% of students watched more than half of the videos, 49% re‐watched at least one video, and 60% watched between 8 a.m.–5 p.m. LMS data showed 14 (13%) students did not watch any videos. Significant differences were found between self‐reported video viewing and matched LMS video data in (1) percentage of videos watched, (2) number of times videos were re‐watched, and (3) most frequent time for watching the videos (p < 0.001 for all).

Conclusion

Technology is a tool that helps instructors more accurately track students’ study habits compared to observation or self‐report. When evaluating time spent watching videos via an LMS, students tend to overestimate the amount of viewing time.
Sleep disorders during pregnancy and postpartum depression: A systematic review and meta‐analysis
Authors: Maghami Mahboobeh , Shariatpanahi Seyyed Payam , Habibi Danial , Heidari‐Beni Motahar , Badihian Negin , Hosseini Mohsen , Kelishadi Roya
Published: May 2021

Background

Postpartum depression (PPD) is one of the most important mental disorders in recent years. However, the effects of prenatal sleep disorders on the development of PPD among pregnant women have not been elucidated. This review aims to provide a summary of the literature evaluating the relation between sleep disorders during pregnancy and PPD.

Method

A systematic literature search was conducted in PubMed, Web of Science, Scopus, Google Scholar, and Embase up to September 2020. All observational studies (cross‐sectional, case–control, and cohort) and studies that assessed the association between sleep disorders during pregnancy and PPD were included. Total sample of 36,873 women from 13 studies was entered to meta‐analysis. An aggregate effect size estimate (odds ratio) was generated using the comprehensive meta‐analysis software. A random effects model was set a priori. Heterogeneity and publication bias were examined using the standard meta‐analytic approaches.

Result

We found maternal sleep disorder increased odds of PPD (point estimate, 3.300; 95% confidence interval [CI], 2.136–5.098;p < .001;n = 13). However, there was significant heterogeneity (Q, 131.250;df, 12;p < .001;I2, 90.857%). The estimated effect size was significant for all categorical studies. According to meta‐regression, no moderating factor (age and publication year) significantly mediated the estimated effect size.

Conclusion

We found a significant relationship between sleep disturbances during pregnancy and PPD. Women with sleep disorders are at an increased risk of developing PPD, which warrants screening pregnant mothers for sleep disturbances. Also, we found that the increasing age in pregnancy was associated with increased risk of PPD.
Oral health‐related quality of life is associated with physical frailty: A cross‐sectional study of Japanese community‐dwelling older adults
Authors: Motoishi Yuya , Yamanashi Hirotomo , Kitamura Masayasu , Hayashida Hideaki , Kawasaki Koji , Nobusue Kenichi , Nonaka Fumiaki , Honda Yukiko , Shimizu Yuji , Kawashiri Shin‐ya , Tamai Mami , Nagata Yasuhiro , Saito Toshiyuki , Maeda Takahiro
Published: May 2021

Background

Physical frailty is related to adverse outcomes, and poor oral health has been linked to malnourishment. Subjective measures of oral health‐related quality of life (OHRQoL) have been used as indicators of the oral health problems of older adults, and they have been associated with malnourishment. This study aimed to assess OHRQoL's association with physical frailty.

Methods

Cross‐sectional study was conducted using data from the Nagasaki Islands Study that enrolled participants aged ≥60 years at Japanese national medical check‐ups from 2014 to 2019. Physical frailty phenotype criteria were determined using the modified Fried frailty phenotype model. OHRQoL was assessed using the Geriatric Oral Health Assessment Index (GOHAI). Dentists conducted clinical dental examinations. Simple correlation and linear regression analyses were performed to investigate the associations of number of physical frailty phenotype criteria with GOHAI and other oral health indicators.

Results

Among 1341 participants with a mean age of 72 years, GOHAI score was significantly associated with number of physical frailty phenotype criteria (B = −0.01, 95% confidence interval: −0.02 to −0.01, p < 0.001). The association remained significant after adjustment for age, sex, body mass index, history of hypertension, history of diabetes mellitus, smoking status, Kessler‐6 score, and number of remaining teeth.

Conclusions

Oral health‐related quality of life was associated with physical frailty in Japanese community‐dwelling older adults.
Is there a role for doravirine in African HIV treatment programmes? A large observational resistance study in South Africa
Authors: Steegen Kim , Moorhouse Michelle , Wensing Annemarie MJ , Venter Willem DF , Hans Lucia
Published: May 2021

Introduction

Dolutegravir has replaced efavirenz in most low‐ and middle‐income countries, due to better tolerability and formidable resistance profile, but dolutegravir side effects suggest alternatives are needed. We evaluated doravirine resistance in South Africa as a first step to assess whether doravirine may replace dolutegravir.

Methods

A retrospective dataset was analysed for predicted doravirine susceptibility, including sequences obtained from three patient groups. First, data from 277 patients initiating antiretroviral treatment (ART) were collected between February 2013 and October 2014 as part of a national survey. Second, data from 788 patients experiencing NNRTI‐based ART failure were obtained between February 2013 and October 2014 as part of a national survey. Third, data derived from 584 patients who had genotypic drug resistance testing requested after NNRT‐based failure as part of individual patient management between January 2016 and December 2019. Pol sequences were generated using validated population‐based in‐house genotyping and submitted to Stanford HIVdb v8.9.

Results and discussion

Less than 5% of patients initiating ART presented with genotypic doravirine resistance, whereas most patients experiencing NNRTI‐based ART failure presented with predicted intermediate (41.0%) or high‐level resistance (43.8%) to doravirine. High‐level resistance to doravirine was commonly predicted by the presence of at least three DRMs (79.7%). The predicted resistance profile to doravirine in ART‐naïve patients is promising, but less so in those experiencing failure to first‐generation NNRTIs. Accumulation of NNRTI DRMs seems to be an important factor in the poor resistance prediction for doravirine.

Conclusions

Although doravirine is approved as initial therapy in patients who are ART‐naïve, it is currently recommended to obtain a genotype prior to the initiation of ART. Clinical studies are needed to ascertain whether predicted resistance profiles in ART naïve and NNRTI‐treated patients translate into poor clinical outcomes, especially in settings where genotypic resistance testing is not available.
A vital technology: Review of the literature on mobile phone use among pastoralists
Authors: Parlasca Martin C.
Published: May 2021

Mobile phones fit well into the lives of pastoralists in low‐income countries. The technology is firmly integrated into most pastoralist communities, affecting and transforming several core activities. Most studies concerned with this relationship, however, have narrow regional and thematic foci. The complementarity or discrepancy between relevant research is unknown, and a critical assessment of the current state of research is lacking. This study identifies, summarizes, and analyzes relevant studies, showing that the literature attests generally positive influences of mobile phones although some negative effects also occur. Effects on pastoralists' income, environmental externalities, and gender roles are not yet sufficiently understood.
SLC25A42‐associated mitochondrial encephalomyopathy: Report of additional founder cases and functional characterization of a novel deletion
Authors: Aldosary Mazhor , Baselm Shahad , Abdulrahim Maha , Almass Rawan , Alsagob Maysoon , AlMasseri Zainab , Huma Rozeena , AlQuait Laila , Al‐Shidi Tarfa , Al‐Obeid Eman , AlBakheet Albandary , Alahideb Basma , Alahaidib Lujane , Qari Alya , Taylor Robert W. , Colak Dilek , AlSayed Moeenaldeen D. , Kaya Namik
Published: May 2021

SLC25A42 is the main transporter of coenzyme A (CoA) into mitochondria. To date, 15 individuals have been reported to have one of two bi‐allelic homozygous missense variants in the SLC25A42 as the cause of mitochondrial encephalomyopathy, of which 14 of them were of Saudi origin and share the same founder variant, c.871A > G:p.Asn291Asp. The other subject was of German origin with a variant at canonical splice site, c.380 + 2 T > A. Here, we describe the clinical manifestations and the disease course in additional six Saudi patients from four unrelated consanguineous families. While five patients have the Saudi founder p.Asn291Asp variant, one subject has a novel deletion. Functional analyses on fibroblasts obtained from this patient revealed that the deletion causes significant decrease in mitochondrial oxygen consumption and ATP production compared to healthy individuals. Moreover, extracellular acidification rate revealed significantly reduced glycolysis, glycolytic capacity, and glycolytic reserve as compared to control individuals. There were no changes in the mitochondrial DNA (mtDNA) content of patient fibroblasts. Immunoblotting experiments revealed significantly diminished protein expression due to the deletion. In conclusion, we report additional patients with SLC25A42‐associated mitochondrial encephalomyopathy. Our study expands the molecular spectrum of this condition and provides further evidence of mitochondrial dysfunction as a central cause of pathology. We therefore propose that this disorder should be included in the differential diagnosis of any patient with an unexplained motor and speech delay, recurrent encephalopathy with metabolic acidosis, intermittent or persistent dystonia, lactic acidosis, basal ganglia lesions and, especially, of Arab ethnicity. Finally, deep brain stimulation should be considered in the management of patients with life altering dystonia.
Use of continuous cranial shape variation in the identification of divergent crocodile species of the genus Mecistops
Authors: Carr Amanda N. , Nestler Jennifer H. , Vliet Kent A. , Brochu Christopher A. , Murray Christopher M. , Shirley Matthew H.
Published: May 2021

The discovery of cryptic biodiversity has blossomed under the advancements of genetic techniques, but species identification via morphology remains crucial to effective conservation efforts. In this study, we tested the use of continuous cranial shape variation in distinguishing the two living species of Mecistops: the West African slender‐snouted crocodile (M. cataphractus) and the Central African slender‐snouted crocodile (M. leptorhynchus). Using a combination of geometric morphometric characters and ratios of linear measurements, we identified statistically significant variation in cranial bone and overall skull shape of mature individuals that corroborates existing molecular and discrete morphological evidence for two distinct, extant species within Mecistops. Specifically, variation in the shape of the nasal appears particularly diagnostic, while ratios involving metrics of snout length to snout width at the premaxillary notch offer distinguishing features easily measured in the field. Because of the complementary results and applications of the morphometric and cranial ratio analyses, we argue that both methodologies remain relevant to species identification. Moreover, we recommend continued cooperation between geneticists and morphologists in diagnosing species of conservation concern.
Plants control soil gas exchanges possibly via mucilage
Authors: Haupenthal Adrian , Brax Mathilde , Bentz Jonas , Jungkunst Hermann F. , Schützenmeister Klaus , Kroener Eva
Published: May 2021

Background: Gaseous matter exchanges in soil are determined by the connectivity of the pore system which is easily clogged by fresh root exudates. However, it remains unclear how a hydrogel (e.g., mucilage) affects soil pore tortuosity and gas diffusion properties when drying.

Aims: The aim of this viewpoint study is to extend the understanding of gas exchange processes in the rhizosphere by (a) relating it to the patterns formed by drying mucilage within pore space and (b) to give a concept of the effect of drying mucilage on soil gas diffusivity using the combination of experimental evidence and simulations.

Methods: To describe the effect of mucilage on soil gas exchanges, we performed gas diffusion experiments on dry soil–mucilage samples and took images of glass beads mixed with mucilage to visualize the formation of mucilage after drying, using Environmental Scanning Electron Microscopy. Finally, we set up simulations to characterize the geometric distribution of mucilage within soil during the drying process.

Results: Experiments of gas diffusion show that mucilage decreases gas diffusion coefficient in dry soil without significantly altering bulk density and porosity. Electron microscopy indicates that during drying mucilage forms filaments and interconnected structures throughout the pore space reducing gas phase connectivity. The evolution of these geometric structures is explained via pore scale modelling based on identifying the elastic strength of rhizodeposition during soil drying.

Conclusion: Our results suggest that releasing mucilage may be a plant adaption strategy to actively alter gas diffusion in soil.
Tourist inspiration and its consequences: The moderating role of neuroticism
Authors: Khoi Nguyen Huu , Le Angelina Nhat‐Hanh , Tran Mai Dong
Published: May 2021

Drawing on the cognitive appraisal theory, this study contributes by investigating how and why tourist inspiration elicits emotional responses of delight and transcendence, which in turn affect the intention to revisit a particular destination under the moderating effect of neuroticism. This study uses PLS‐SEM to test the proposed hypotheses on a dataset of 238 international tourists traveling to Vietnam. The results indicate that the states of inspired‐by and inspired‐to have positive effects on delight and transcendence, which in turn exert a positive influence on the intention to revisit. Neuroticism has negative moderating effects on the relationship between tourist inspiration and emotional responses.
Hearing loss in inner ear and systemic autoimmune disease: A systematic review of post‐cochlear implantation outcomes
Authors: Lee Jonathan , Biggs Kirsty , Muzaffar Jameel , Bance Manohar , Monksfield Peter
Published: May 2021

Objectives

To assess outcomes following cochlear implantation (CI) in patients with hearing loss secondary to primary or secondary autoimmune inner ear disease (AIED).

Methods

A systematic review and narrative synthesis was completed according to PRISMA guidelines. Databases searched included MEDLINE, PubMed, EMBASE, Web of Science, Cochrane Collection, and ClinicalTrials.gov. No limits were placed on year of publication or language.

Results

A total of 551 studies were identified, of which 29 were included after removal of duplicates, and screening the title, abstract, and full text. All except one study were OCEBM grade IV. 114 of 115 patients displayed improvement in hearing following cochlear implantation. With implant use, roughly a third of these patients had hearing that improved over time, a third improved and plateaued, and a third remained stable. There was no additional risk of perioperative complications found in AIED patients compared what is generally accepted in general cochlear implantation, although two episodes of device failure after 6 months were noted, and four patients with secondary AIED displayed poor initial audiological outcomes.

Conclusion

CI in both primary and secondary AIED provides marked improvement in hearing. Early CI may be a valid management option, provide long‐lasting hearing in patients and reduce the side effects of long‐term systemic immunosuppressants. However, patients should be counseled residual hearing may be lost if there is cochlear ossification or fibrosis which may make implant insertion more traumatic.

Level of Evidence

NA.
Self‐Assembly or Coassembly of Multiresponsive Histidine‐Containing Elastin‐Like Polypeptide Block Copolymers
Authors: Abdelghani Mona , Shao Jingxin , Le Duc H. T. , Wu Hanglong , van Hest Jan C. M.
Published: May 2021

In this study a histidine containing elastin‐like polypeptide (ELP) diblock copolymer is described with multiresponsive assembly behavior. Self‐assembly into micelles is examined by two methods. First, the self‐assembly is triggered by the addition of divalent metal ions, with Zn2+ being the most suitable one. Increasing the Zn2+ concentration stabilizes the nanoparticles over a large temperature window (4–45 °C). This diblock exhibits furthermore pH‐responsiveness, and particles disassemble under mildly acidic conditions. Second, the coassembly of this ELP with a diblock ELP is examined, which is not responsive to pH and metal ions. Coassembly is triggered by heating the ELPs quickly above the transition temperature of the less hydrophobic block, which results in stable nanoparticles without the need to add metal ions. This novel ELP system offers a versatile modular nanocarrier platform that can respond to different stimuli and can be tuned effectively.
Zirconium‐Embedded Polyhedral Oligomeric Silsesquioxane Containing Phosphaphenanthrene‐Substituent Group Used as Flame Retardants for Epoxy Resin Composites
Authors: Zeng Birong , He Kaibin , Wu Haiyang , Ye Jianyu , Zheng Xianghong , Luo Weiang , Xu Yiting , Yuan Conghui , Dai Lizong
Published: May 2021

A zirconium hybrid polyhedral oligomeric silsesquioxane derivative (Zr–POSS–bisDOPO) is synthesized by the corner‐capping and Kabachnik–Fields reactions. It is characterized by Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy (NMR), and then used as a flame retardant in diglycidyl ether of bisphenol A (DGEBA) to endow epoxy resin (EP) with flame retardancy. The flame retardancy, thermal stability, and mechanical properties of the cured EP/Zr–POSS–bisDOPO composites are investigated. The results show that when Zr–POSS–bisDOPO is added by 5–7 wt%, the EP/Zr–POSS–bisDOPO composites pass the UL‐94 V‐0 rating test. In addition, they have a better flame‐retardant effect than pure EP. The combination of Zr atom embedded in the SiO cubic cage and the two phosphaphenanthrene substituent groups in one corner of cubic cage is expected to realize the Zr/Si/P ternary intramolecular hybrid synergistic effect and achieve the possibility of dispersing metal–POSS cages at a sub‐micrometer‐scale level into polymer matrix. It also proves that Zr–POSS–bisDOPO produces phosphorus‐containing free radicals and terminates the chain reactions in gas phase. Meanwhile the SiOSi and ZrO units are retained in the solid phase, which promote the char formation and enhance the flame retardancy. This kind of Zr‐doped POSS will be helpful for developing the new metal–POSS hybrid flame‐retardant and polymer composites.
Ultra‐Stretchable Monofilament Flexible Sensor with Low Hysteresis and Linearity based on MWCNTs/Ecoflex Composite Materials
Authors: Zhang Yanlin , Zhu Xubin , Liu Yitao , Liu Li , Xu Qiang , Liu Hao , Wang Wei , Chen Li
Published: May 2021

Wearable human–computer interaction equipment is a common technology, which can improve the comfort, convenience, and safety of the human body, and also can monitor human health. The flexible and wearable tensile sensor can be conveniently installed on clothes or directly connected to the body. This provides a convenient, timely, and portable solution for the detection of human motion. Therefore, wearable electronic equipment is gaining more attention. In this paper, a highly stretchable, flexible, and sensitive strain sensor which is based on multi‐walled carbon nanotubes/Ecoflex nanocomposites is reported. A monofilament tensile sensor obtains good linearity (10.77%), low hysteresis (1.63%), good stability (6000 cycles under 100% strain), and ultra‐high strain range (ε = 1300%). This ultra‐stretchable sensor has potential applications in human motion monitoring, medical rehabilitation, health monitoring, human–computer interaction, and soft robots.
Advances in Electrospun Fiber‐Based Flexible Nanogenerators for Wearable Applications
Authors: Arica Tugce A. , Isık Tugba , Guner Tugrul , Horzum Nesrin , Demir Mustafa M.
Published: May 2021

In today's digital age, the need and interest in personal and portable electronics shows a dramatic growth trend in daily life parallel to the developments in sensors technologies and the internet. Wearable electronics that can be attached to clothing, accessories, and the human body are one of the most promising subfields. The energy requirement for the devices considering the reduction in device sizes and the necessity of being flexible and light, the existing batteries are insufficient and nanogenerators have been recognized a suitable energy source in the last decade. The mechanical energy created by the daily activities of the human body is an accessible and natural energy source for nanogenerators. Fiber‐structured functional materials contribute to the increase in energy efficiency due to their effective surface to volume ratio while providing the necessary compatibility and comfort for the movements in daily life with its flexibility and lightness. Among the potential solutions, electrospinning stands out as a promising technique that can meet these requirements, allowing for simple, versatile, and continuous fabrication. Herein, wearable electronics and their future potential, electrospinning, and its place in energy applications are overviewed. Moreover, piezoelectric, triboelectric, and hybrid nanogenerators fabricated or associated with electrospun fibrous materials are presented.
Clinical Profiles and Mortality of COVID‐19 Inpatients with Parkinson's Disease in Germany
Authors: Scherbaum Raphael , Kwon Eun Hae , Richter Daniel , Bartig Dirk , Gold Ralf , Krogias Christos , Tönges Lars
Published: May 2021

Background

Comprehensive, nationwide data regarding Parkinson's disease (PD) hospitalizations, coronavirus disease 2019 (COVID‐19) in‐hospital frequency, and COVID‐19‐associated inpatient mortality during the first wave of the COVID‐19 pandemic are not available.

Objective

To provide a nationwide analysis on hospitalized PD patients in Germany and evaluate the impact of the COVID‐19 pandemic.

Methods

We conducted a cross‐sectional study using an administrative claims database covering 1468 hospitals and 5,210,432 patient hospitalizations including a total of 30,872 COVID‐19+ cases between January 16 and May 15, 2020.

Results

Compared to 2019, hospitalizations for PD transiently decreased by up to 72.7% in 2020. COVID‐19 frequency was significantly higher in the population of 64,434 PD patients (693 being COVID‐19+) than in non‐PD patients (1.1% vs. 0.6%, P < 0.001), especially in subjects with advanced age (≥ 65 years). Regarding established COVID‐19 risk comorbidities, COVID‐19+ inpatients with PD showed higher incidences than non‐PD COVID‐19+ subjects, particularly hypertension and chronic kidney disease. Advanced age and male sex were significantly more frequent in COVID‐19+ than in COVID‐19− PD patients. The COVID‐19 inpatient mortality rate was much higher in PD patients than in non‐PD patients (35.4% vs. 20.7%, P < 0.001), especially in patients aged 75–79 years. Of note, overall inpatient mortality of PD patients was significantly higher in 2020 than in 2019 (5.7% vs. 4.9%, P < 0.001).

Conclusions

PD inpatients are more frequently affected by COVID‐19 and suffer from increased COVID‐19‐associated mortality in comparison to non‐PD patients. More comprehensive studies are needed to assess the significance of associated comorbidities for COVID‐19 risk and mortality in PD. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
Is Persistent Motor or Vocal Tic Disorder a Milder Form of Tourette Syndrome?
Authors: Claudio‐Campos Karla , Stevens Daniel , Koo Sang‐Wahn , Valko Alexa , Bienvenu Oscar Joseph , Budman Cathy B. , Cath Danielle C. , Darrow Sabrina , Geller Daniel , Goes Fernando S. , Grados Marco A. , Greenberg Benjamin D. , Greenberg Erica , Hirschtritt Matthew E. , Illmann Cornelia , Ivankovic Franjo , King Robert A. , Knowles James A. , Krasnow Janice , Lee Paul C. , Lyon Gholson J. , McCracken James T. , Robertson Mary M. , Osiecki Lisa , Riddle Mark A. , Rouleau Guy , Sandor Paul , Nestadt Gerald , Samuels Jack , Scharf Jeremiah M. , Mathews Carol A. ,   for the Tourette Association of America International Consortium for Genetics (TAAICG) and the OCD Collaborative Genetics Association Study (OCGAS)
Published: May 2021

Background

Persistent motor or vocal tic disorder (PMVT) has been hypothesized to be a forme fruste of Tourette syndrome (TS). Although the primary diagnostic criterion for PMVT (presence of motor or vocal tics, but not both) is clear, less is known about its clinical presentation.

Objective

The goals of this study were to compare the prevalence and number of comorbid psychiatric disorders, tic severity, age at tic onset, and family history for TS and PMVT.

Methods

We analyzed data from two independent cohorts using generalized linear equations and confirmed our findings using meta‐analyses, incorporating data from previously published literature.

Results

Rates of obsessive–compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD) were lower in PMVT than in TS in all analyses. Other psychiatric comorbidities occurred with similar frequencies in PMVT and TS in both cohorts, although meta‐analyses suggested lower rates of most psychiatric disorders in PMVT compared with TS. ADHD and OCD increased the odds of comorbid mood, anxiety, substance use, and disruptive behaviors, and accounted for observed differences between PMVT and TS. Age of tic onset was approximately 2 years later, and tic severity was lower in PMVT than in TS. First‐degree relatives had elevated rates of TS, PMVT, OCD, and ADHD compared with population prevalences, with rates of TS equal to or greater than PMVT rates.

Conclusions

Our findings support the hypothesis that PMVT and TS occur along a clinical spectrum in which TS is a more severe and PMVT a less severe manifestation of a continuous neurodevelopmental tic spectrum disorder. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
Longitudinal Analysis of Multiple Neurotransmitter Metabolites in Cerebrospinal Fluid in Early Parkinson's Disease
Authors: Kremer Thomas , Taylor Kirsten I. , Siebourg‐Polster Juliane , Gerken Thomas , Staempfli Andreas , Czech Christian , Dukart Juergen , Galasko Douglas , Foroud Tatiana , Chahine Lana M. , Coffey Christopher S. , Simuni Tanya , Weintraub Daniel , Seibyl John , Poston Kathleen L. , Toga Arthur W. , Tanner Caroline M. , Marek Kenneth , Hutten Samantha J. , Dziadek Sebastian , Trenkwalder Claudia , Pagano Gennaro , Mollenhauer Brit
Published: May 2021

Background

Cerebrospinal fluid (CSF) levels of monoamine metabolites may represent biomarkers of Parkinson's disease (PD).

Objective

The aim of this study was quantification of multiple metabolites in CSF from PD versus healthy control subjects (HCs), including longitudinal analysis.

Methods

Absolute levels of multiple monoamine metabolites in CSF were quantified by liquid chromatography coupled with tandem mass spectrometry from 161 individuals with early PD and 115 HCs from the Parkinson's Progression Marker Initiative and de novo PD (DeNoPA) studies.

Results

Baseline levels of homovanillic acid (HVA) and 3,4‐dihydroxyphenylacetic acid (DOPAC) were lower in individuals with PD compared with HCs. HVA levels correlated with Movement Disorder Society Unified Parkinson's Disease Rating Scale total scores (P < 0.01). Both HVA/dopamine and DOPAC/dopamine levels correlated with caudate nucleus and raw DOPAC with putamen dopamine transporter single‐photon emission computed tomography uptake ratios (P < 0.01). No metabolite changed over 2 years in drug‐naive individuals, but some changed on starting levodopa treatment.

Conclusions

HVA and DOPAC CSF levels mirrored nigrostriatal pathway damage, confirming the central role of dopaminergic degeneration in early PD. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
Expectations of Benefit in a Trial of a Candidate Disease‐Modifying Treatment for Parkinson Disease
Authors: Mestre Tiago A. , Macklin Eric A. , Ascherio Alberto , Ferreira Joaquim J. , Lang Anthony E. , Schwarzschild Michael A. ,   the Parkinson Study Group SURE‐PD3 Investigators
Published: May 2021

Background

Expectations of benefit have an important therapeutic impact. How well study participants understand the concept of slowing disease progression and how their expectations of benefit are shaped in related clinical trials is not well known.

Objective

We aimed to assess expectancy and treatment arm preference of participants in a disease‐modification trial in Parkinson disease (PD).

Methods

Participant expectations and treatment preference were assessed before treatment randomization in the SURE‐PD3 trial (NCT02642393).

Results

We included 297 PD patients (0.71 ± 0.67 years after diagnosis). Pre‐randomization, 90% of participants expressed a preference for inosine (active treatment) allocation (n = 266/297), and 53% (n = 158) expected to be “somewhat” or “a lot better” in their symptoms over 2 years of treatment with inosine.

Conclusions

Participants of a disease‐modification trial in PD had likely unrealistic expectations of benefit (ie, improvement in symptoms over years), which may affect clinical trial interpretation and calls for improved education in future disease‐modification trials in PD. © 2021 International Parkinson and Movement Disorder Society
Onset of Skin, Gut, and Genitourinary Prodromal Parkinson's Disease: A Study of 1.5 Million Veterans
Authors: Scott Gregory D. , Lim Miranda M. , Drake Matthew G. , Woltjer Randy , Quinn Joseph F.
Published: May 2021

Background

Prodromal Parkinson's disease of skin, genitourinary, and gastrointestinal systems offers a unique window for understanding early disease pathogenesis and developing disease modifying treatments. However, prior studies are limited by incomplete timing information, small sample size, and lack of adjustment for known confounders. Verifying prodromal timing and identifying new disorders in these accessible organs is critically important given their broad use.

Objective

We aimed to measure onset timing for gastrointestinal, genitourinary, and skin disorders in a large, nationwide clinically characterized cohort of 1.5 million participants.

Methods

Patients with Parkinson's disease (n = 303,693) were identified using diagnostic codes in the medical records database of the United States Veterans Affairs healthcare system and were compared 4:1 with matched controls. Disorder prevalence and estimated onset times were assessed for 20 years preceding diagnosis.

Results

The earliest significantly increased prodromal disorders were gastroesophageal reflux, sexual dysfunction, and esophageal dyskinesia at 17, 16, and 15 years before diagnosis. Estimated onset times for each disorder occurred 5.5 ± 3.4 years before the first measured increase. The earliest estimated onset times were smell/taste, upper gastrointestinal tract, and sexual dysfunction at 20.9, 20.6, and 20.1 years before diagnosis. Onset times for constipation and urinary dysfunction were notably longer by 7 and 9 years compared to prior studies in sleep disorder patients. Dermatophytosis and prostatic hypertrophy were identified as new high prevalence prodromal disorders.

Conclusions

Gastrointestinal, genitourinary, and skin disorders manifest decades before diagnosis of Parkinson's disease, reiterating their potential as sites for developing early diagnostic testing and understanding pathogenesis.
A novel essential splice site variant in SPTB in a large hereditary spherocytosis family
Authors: Nieminen Taina T. , Liyanarachchi Sandya , Comiskey Daniel F. , Wang Yanqiang , Li Wei , Hendrickson Isabella V. , Brock Pamela , de la Chapelle Albert , He Huiling
Published: May 2021

Background

We studied a large family with 22 individuals affected with autosomal dominant hereditary spherocytosis (HS).

Methods

Genome‐wide linkage, whole‐genome sequencing (WGS), Sanger sequencing, RT‐PCR, and ToPO TA cloning analyses were performed.

Results

We revealed a heterozygous G>A transition in the 14q23 locus, at position +1 of the intron 8 donor splice site of the spectrin beta, erythrocytic (SPTB) gene. This splice variant (SPTB c.1064+1G>A) was confirmed by Sanger sequencing and showed complete co‐segregation with HS in the family. Further RT‐PCR reactions and sequencing analysis indicated that the variant leads to the exclusion of exon 8 and subsequent frameshift in exon 9 and a premature stop codon in SPTB. Translation of the altered allele would lead to a truncation with a loss of all spectrin repeat domains in SPTB protein.

Conclusion

This variant is novel and has not been found in any databases. We propose that this splice variant explains the spherocytosis phenotype observed in this large family.
Ion exchange for halide perovskite: From nanocrystal to bulk materials
Authors: Jiang Haotian , Cui Siqi , Chen Yu , Zhong Haizheng
Published: May 2021

Halide perovskite, an ionic semiconductor, with the typically structural composition of ABX3 has become the extremely popular star in optoelectronics due to its superior photophysical properties and easily solution processing. In comparison with the traditional semiconductors, the perovskite possesses a low crystal formation energy with facile solution synthesis, which results into its soft and dynamic crystal lattice. Therefore, the post‐synthetic composition tuning via ion exchange has been proved to be an effective technique to introduce heteroatoms into perovskite lattice. In this review, we summarize the recent progress on ion exchange of halide perovskites, including mechanisms, methods, as well as different scales from low‐dimensional nanoscale to bulk crystal. Besides, we also briefly discuss the prospective of ion exchange for halide perovskites, and hope it benefit for the structural design and compositional optimization in halide perovskites for various optoelectronic applications.
Risk of obstetric anal sphincter injury with fundal pressure in second stage of labor: Transperineal ultrasound study
Authors: Öncü Hande N. , Aydın Serdar , Arıoğlu Çağrı
Published: May 2021

Aims

Clinical management of the second stage of labor and effectiveness of preventive measures for severe perineal tears are controversial. The aim of this study was to evaluate the effect of using uterine fundal pressure during the second stage of delivery on obstetric anal sphincter injury (OASI), among primiparous women using three‐dimensional (3D) transperineal ultrasonography.

Methods

A total of 73 women who had their first vaginal birth were included in the study, the fundal pressure group included women where the fundal pressure maneuver was applied (n = 37); and the control group included women who delivered spontaneously without fundal pressure (n = 36). Tomographic ultrasound imaging with 3D transperineal assessment was performed within 48 h of delivery, internal anal sphincter (IAS) and external anal sphincter (EAS) defect were determined.

Results

Five (13.5%) women in the fundal pressure group, seven (20%) women in the control group had complete EAS defect (p = 0.4). Complete IAS defect was observed in one (2.7%) woman in the fundal pressure group and two (5.7%) women in the control group (p = 0.5). A Half‐moon sign was observed in one woman in both groups (p = 0.9). The rate of other signs was similar in both groups. Multivariate regression models revealed that none of age, fetal birth weight, episiotomy, length of the second stage of labor, fundal pressure application status, and number were independent predictors of complete IAS or EAS defect.

Conclusion

Fundal pressure with mediolateral episiotomy during the second stage of delivery does not increase the rate of OASI detected with ultrasonography.
Influence of the blending method over the thermal and mechanical properties of biodegradable polylactic acid/polyhydroxybutyrate blends and their wood biocomposites
Authors: Pérez‐Fonseca Aida A. , Herrera‐Carmona Vanessa S. , Gonzalez‐García Yolanda , Martín del Campo Alan S. , González‐López Martín E. , Ramírez‐Arreola Daniel E. , Robledo‐Ortíz Jorge R.
Published: May 2021

This study focused on the effect of the processing method on the thermal, mechanical, and biodegradation properties of polylactic acid/polyhydroxybutyrate (PLA/PHB) blends and their wood biocomposites. The blending techniques were dry‐blending or twin‐screw extrusion, both followed by compression molding. PLA/PHB blends were prepared using 15 and 25% wt. of PHB and biocomposites with 20 and 30% wt. of wood particles. Moreover, a compatibilizer was used during the extrusion process to achieve better matrix‐fiber adhesion. The results showed that the crystallinity of PLA significantly increased with PHB and wood, especially after twin‐screw extrusion. The best results in tensile, flexural, and impact strength were obtained with the extruded and compatibilized PLA/PHB blends, with values higher than the neat biopolymers. The compatibilized biocomposite with 15% wt. PHB, and 20% wt. wood particles showed higher tensile, flexural, and impact properties than PLA. The biodegradation test showed that all samples were disintegrated (above 40%) after 40 days in compost medium, observing slight decreases in the biodegradation rate when PHB or wood particles were added. Even when the lower mechanical properties were obtained with the dry‐blending technique, they are still competitive for different applications, providing the possibility to produce blends and biocomposites, avoiding the extrusion process that requires more energy consumption and longer processing times.
Phase stability of colloidal spheres mixed with supramolecular rod‐like polymers
Authors: Peters Vincent F. D. , Vis Mark , Tuinier Remco
Published: May 2021

Mixtures of colloids and supramolecular polymers exhibit stimuli‐responsive phase behavior. In previous work (Peters and Tuinier, Physica A 510, 233 [2018]) the polymers were treated as fully flexible chains, while in experimental systems supramolecular polymers may have a certain degree of stiffness. Here we predict that for stiff rod‐like supramolecular polymers phase separation can occur at much lower polymer concentrations than for flexible supramolecular polymers. Additionally, it is demonstrated that colloid–polymer interactions can significantly influence the equilibrium polymer size distribution, however this does not strongly affect the phase behavior of the mixture. At the low polymer concentrations at which the system already gets unstable, the effect of excluded volume interactions between polymers chains themselves is small. Finally, for an experimental system it is predicted that a variety of re‐entrant phase transitions may be observed within a realistic temperature range as illustrated by a specific example.
Predicting the potential for spread of emerald ash borer (Agrilus planipennis) in Great Britain: What can we learn from other affected areas?
Authors: Webb Cerian R. , Mona Tamas , Gilligan Christopher A.
Published: May 2021

Societal Impact Statement

Emerald ash borer (EAB) is thought to have arrived in North America and European Russia at least 10 years prior to detection. Despite heightened awareness that EAB could invade Great Britain (GB), detection in the early stages of establishment is difficult, and initial symptoms might be mistaken for Chalara ash dieback. Our results suggest that if partial resistance to EAB inFraxinus excelsiordoes not significantly dampen EAB population dynamics, then EAB could establish and spread across large parts of southern England within a relatively short time period; however, further northern spread may be limited by the relatively cool climate.

The accidental introduction of emerald ash borer (EAB) to North America and European Russia in the 1990s has resulted in an ongoing crisis with millions of ash trees damaged and killed at immense economic and social cost. Improving our understanding of how rapidly the pest might spread should it enter Great Britain (GB) plays an essential part in planning for a potential outbreak.

Two metrics are used to investigate the potential dynamics of EAB in GB: the observed rate of spread in the North American and Russian regions; and the relationship between degree days and emergence that may determine environmental suitability and whether the life cycle is univoltine or semivoltine.

The pest is still spreading in North America and European Russia with an overall average rate of spread between 2002 and 2018 of approximately 50 km a year. Early detection of the pest is difficult, but a similar delay in detection to that in North America would result in a costly and hard to control outbreak. Comparison of degree days between regions suggests that a semivoltine life cycle is most likely in most areas of GB but spread maybe limited by the relatively cool climate in parts of GB.

There are several potentially important differences in the biophysical environment in GB compared with North America and European Russia. However, the speed with which it has invaded these areas highlights the need for early surveillance and mitigations to minimise human‐mediated spread of this highly destructive pest.