bluuebunny/crossref_metadata_2025 huggingface dataset:
ptFVa (
Pseudonaja Textilis
Venom-Derived Factor Va) Retains Structural Integrity Following Proteolysis by Activated Protein C
Authors: Schreuder Mark , Liu Xiaosong , Cheung Ka Lei , Reitsma Pieter H. , Nicolaes Gerry A.F. , Bos Mettine H.A.
Published: June 2021

Objective:

The Australian snake venom ptFV (
Pseudonaja textilis
venom-derived factor V) variant retains cofactor function despite APC (activated protein C)-dependent proteolysis. Here, we aimed to unravel the mechanistic principles by determining the role of the absent Arg306 cleavage site that is required for the inactivation of FVa (mammalian factor Va).

Approach and Results:

Our findings show that in contrast to human FVa, APC-catalyzed proteolysis of ptFVa at Arg306 and Lys507 does not abrogate ptFVa cofactor function. Remarkably, the structural integrity of APC-proteolyzed ptFVa is maintained indicating that stable noncovalent interactions prevent A2-domain dissociation. Using Molecular Dynamics simulations, we uncovered key regions located in the A1 and A2 domain that may be at the basis of this remarkable characteristic.

Conclusions:

Taken together, we report a completely novel role for uniquely adapted regions in ptFVa that prevent A2 domain dissociation. As such, these results challenge our current understanding by which strict regulatory mechanisms control FVa activity.
Functional Calsequestrin-1 Is Expressed in the Heart and Its Deficiency Is Causally Related to Malignant Hyperthermia-Like Arrhythmia
Authors: Sun Zhipeng , Wang Luqi , Han Lu , Wang Yue , Zhou Yuan , Li Qiang , Wu Yongquan , Talabieke Shaletanati , Hou Yunlong , Wu Lulin , Liu Ronghua , Fu Zhiping , You Hongjie , Li Bai-Yan , Zheng Yuanyuan , Luo Dali
Published: June 2021

Background:

Calsequestrins (Casqs), comprising the Casq1 and Casq2 isoforms, buffer Ca
2+
and regulate its release in the sarcoplasmic reticulum of skeletal and cardiac muscle, respectively. Human inherited diseases associated with mutations in
CASQ1
or
CASQ2
include malignant hyperthermia/environmental heat stroke (MH/EHS) and catecholaminergic polymorphic ventricular tachycardia. However, patients with an MH/EHS event often experience arrhythmia for which the underlying mechanism remains unknown.

Methods:

Working hearts from conventional (
Casq1
-KO) and cardiac-specific (
Casq1
-CKO)
Casq1
knockout mice were monitored in vivo and ex vivo by ECG and electric mapping, respectively. MH was induced by 2% isoflurane and treated intraperitoneally with dantrolene. Time-lapse imaging was used to monitor intracellular Ca
2+
activity in isolated mouse cardiomyocytes or neonatal rat ventricular myocytes with knockdown, overexpression, or truncation of the
Casq1
gene. Conformational change in both Casqs was determined by cross-linking Western blot analysis.

Results:

Like patients with MH/EHS,
Casq1
-KO and
Casq1
-CKO mice had faster basal heart rate and ventricular tachycardia on exposure to 2% isoflurane, which could be relieved by dantrolene. Basal sinus tachycardia and ventricular ectopic electric triggering also occurred in
Casq1
-KO hearts ex vivo. Accordingly, the ventricular cardiomyocytes from
Casq1
-CKO mice displayed dantrolene-sensitive increased Ca
2+
waves and diastole premature Ca
2+
transients/oscillations on isoflurane. Neonatal rat ventricular myocytes with Casq1-knockdown had enhanced spontaneous Ca
2+
sparks/transients on isoflurane, whereas cells overexpressing Casq1 exhibited decreased Ca
2+
sparks/transients that were absent in cells with truncation of 9 amino acids at the C terminus of Casq1. Structural evaluation showed that most of the Casq1 protein was present as a polymer and physically interacted with ryanodine receptor-2 in the ventricular sarcoplasmic reticulum. The Casq1 isoform was also expressed in human myocardium. Mechanistically, exposure to 2% isoflurane or heating at 41 °C induced Casq1 oligomerization in mouse ventricular and skeletal muscle tissues, leading to a reduced Casq1/ryanodine receptor-2 interaction and increased ryanodine receptor-2 activity in the ventricle.

Conclusions:

Casq1 is expressed in the heart, where it regulates sarcoplasmic reticulum Ca
2+
release and heart rate. Casq1 deficiency independently causes MH/EHS-like ventricular arrhythmia by trigger-induced Casq1 oligomerization and a relief of its inhibitory effect on ryanodine receptor-2–mediated Ca
2+
release, thus revealing a new inherited arrhythmia and a novel mechanism for MH/EHS arrhythmogenesis.
Pravastatin Versus Placebo in Pregnancies at High Risk of Term Preeclampsia
Authors: Döbert Moritz , Varouxaki Anna Nektaria , Mu An Chi , Syngelaki Argyro , Ciobanu Anca , Akolekar Ranjit , De Paco Matallana Catalina , Cicero Simona , Greco Elena , Singh Mandeep , Janga Deepa , del Mar Gil Maria , Jani Jacques C. , Bartha José Luis , Maclagan Kate , Wright David , Nicolaides Kypros H.
Published: June 2021

Background:

Effective screening for term preeclampsia is provided by a combination of maternal factors with measurements of mean arterial pressure, serum placental growth factor, and serum soluble fms-like tyrosine kinase-1 at 35 to 37 weeks of gestation, with a detection rate of ≈75% at a screen-positive rate of 10%. However, there is no known intervention to reduce the incidence of the disease.

Methods:

In this multicenter, double-blind, placebo-controlled trial, we randomly assigned 1120 women with singleton pregnancies at high risk of term preeclampsia to receive pravastatin at a dose of 20 mg/d or placebo from 35 to 37 weeks of gestation until delivery or 41 weeks. The primary outcome was delivery with preeclampsia at any time after randomization. The analysis was performed according to intention to treat.

Results:

A total of 29 women withdrew consent during the trial. Preeclampsia occurred in 14.6% (80 of 548) of participants in the pravastatin group and in 13.6% (74 of 543) in the placebo group. Allowing for the effect of risk at the time of screening and participating center, the mixed-effects Cox regression showed no evidence of an effect of pravastatin (hazard ratio for statin/placebo, 1.08 [95% CI, 0.78–1.49];
P
=0.65). There was no evidence of interaction between the effect of pravastatin, estimated risk of preeclampsia, pregnancy history, adherence, and aspirin treatment. There was no significant between-group difference in the incidence of any secondary outcomes, including gestational hypertension, stillbirth, abruption, delivery of small for gestational age neonates, neonatal death, or neonatal morbidity. There was no significant between-group difference in the treatment effects on serum placental growth factor and soluble fms-like tyrosine kinase-1 concentrations 1 and 3 weeks after randomization. Adherence was good, with reported intake of ≥80% of the required number of tablets in 89% of participants. There were no significant between-group differences in neonatal adverse outcomes or other adverse events.

Conclusions:

Pravastatin in women at high risk of term preeclampsia did not reduce the incidence of delivery with preeclampsia.

Registration:

URL:
https://www.isrctn.com
; Unique identifier ISRCTN16123934.
The spider genus Patrera Simon (Araneae: Dionycha, Anyphaeninae) in the Atlantic Forest biome, with the description of one new species from Brazil
Authors: OLIVEIRA LUIZ FERNANDO M. , BRESCOVIT ANTONIO D.
Published: June 2021

The species of Patrera Simon, 1903 from Brazilian Atlantic Forest biome are revised. With more than 2715 specimens examined, nine species were found and, of these, only one new species is described, Patrera teresopolis n. sp. from state of Rio de Janeiro. The other valid names were described by a single author: Patrera procera (Keyserling, 1891), P. longipes (Keyserling, 1891), P. virgata (Keyserling, 1891), P. cita (Keyserling, 1891), P. tensa (Keyserling, 1891), n. comb., P. opertanea (Keyserling, 1891), n. comb., P. concolor (Keyserling, 1891), n. comb. and P. recentissima (Keyserling, 1891), n. comb. (Later four here transferred from Teudis O. Pickard-Cambridge, 1896) and P. pellucida (Keyserling, 1891), n. comb. (here transferred from Sillus F.O. Pickard-Cambridge, 1900). The males of Patrera opertanea, P. pellucida and P. recentissima are described for the first time. The species Teudis itatiayae Mello-Leitão, 1915 and Sillus delicatus Mello-Leitão, 1922 are synonymized with P. longipes; Osoriella pallidoemanu Mello-Leitão, 1926 is synonymized with P. concolor. All species are described, illustrated and mapped. The known distribution of Patrera procera and P. longipes is expanded to Argentina and that of Patrera procera to Paraguay.
The Japanese species of the genus Gracilentulus (Protura: Acerentomidae)
Authors: NAKAMURA OSAMI
Published: June 2021

The Japanese members of the proturan genus Gracilentulus comprise five species: G. aokii Imadaté, G. chichibuensis Nakamura, G. macrotarsus sp. nov., G. microtrichus sp. nov., and G. europaeus Szeptycki. In the present study, the new Gracilentulus species are described while G. europaeus is described based on Japanese specimens. Gracilentulus europaeus belongs to the “gracilis” group, which was recorded in Japan for the first time herein. Supplementary notes are provided on G. aokii and G. chichibuensis. A key to the species that lack sensillum b’ on the foretarsus is also provided.
Four new species of the genus Trichodromeus Luze, 1903 from Nepal and Pakistan (Coleoptera: Staphylinidae: Omaliinae: Anthophagini)
Authors: SHAVRIN ALEXEY V.
Published: June 2021

Four new species of the genus Trichodromeus Luze, 1903 are described and illustrated: T. acutipenis Shavrin, sp.n., T. jaegeri Shavrin, sp.n. and T. kaliyuga Shavrin, sp.n. from Nepal, and T. trilobatus Shavrin, sp.n. from Pakistan (Azad Kashmir). A key to species and distribution maps for all Nepalese species are provided. The genus is recorded from Nepal for the first time.
Alpha-taxonomy and phylogeny of African Junoniini butterflies based on morphological data, with an emphasis on genitalia, and COI barcode (Lepidoptera: Nymphalidae)
Authors: PYRCZ TOMASZ W. , FLORCZYK KLAUDIA , COLLINS STEVE , SÁFIÁN SZABOLCS , MAHECHA-J. OSCAR , LACHOWSKA-CIERLIK DOROTA
Published: June 2021

The tribe Junoniini is a predominantly Paleotropical group of the cosmopolitan butterfly subfamily Nymphalinae (Nymphalidae), with highest diversity in the Afrotropical region. Its systematics and relationships are not entirely resolved. Question marks remain concerning the validity of some genera; and the apparently close relationship between the Indo-Australian genus Yoma and the Afrotropical Protogoniomorpha, as evidenced by molecular phylogenies, remains a puzzle. Here, we present a cladistic analysis, based on 42 characters of the male and female genitalia of 41 species of Junoniini belonging to six genera, nearly all of them continental Afrotropical, and 3 species of two Indo-Australian genera Yoma and Rhinopalpa. A ML COI-based tree is produced for 36 species of Afrotropical Junoniini and Yoma. The molecular data are consistent with previous studies. However, morphological analysis does not confirm a close relationship between Protogoniomorpha and Yoma. Despite the evolution of a number of modifications, the male genitalia within all genera and species of the Junoniini share a cohesive build plan, in particular a transformed sacculus, from which Yoma is highly divergent. The position of the genus Kamilla, previously synonymized with Junonia, is discussed. Three East African coast taxa, Junonia elgiva stat. reinst., Protogoniomorpha nebulosa stat. reinst. and Salamis amaniensis stat. reinst., and one from central Africa, Precis silvicola stat. reinst. are raised to species level, based on comparative analysis of their male genitalia.
Contribution to the study of Epeorus Eaton, 1881 (Ephemeroptera: Heptageniidae) from India
Authors: VASANTH M. , SELVAKUMAR C. , SUBRAMANIAN K. A. , SIVARAMAKRISHNAN K. G. , SINHA BIKRAMJIT
Published: June 2021

Seven species of the genus Epeorus Eaton, 1881 are described so far from India of which redescription is attempted herein for 3 species viz. E. (C.) psi Eaton 1883, E. (E.) gilliesi Braasch 1981, E. (E.) petersi Sivaruban, Venkataraman & Sivaramakrishnan 2013 based on the fresh collections. Four species viz., E. (E.) aculeatus Braasch 1990, E. (E.) bifurcatus Braasch & Soldán 1979, E. (E.) unicornutus Braasch 2006 and E. (E.) unispinosus Braasch 1980 are new records to this country. Totally, 11 species of the genus Epeorus from India are dealt with herein of which six belongs to the subgenus Epeorus viz. E. (E.) aculeatus Braasch 1990, E. (E.) bifurcatus Braasch & Soldán 1979, E. (E.) gilliesi Braasch, 1981 and E. (E.) petersi Sivaruban, Venkataraman & Sivaramakrishnan 2013, E. (E.) unispinosus Braasch 1980, E. (E.) unicornutus Braasch 2006 and four to the subgenus Caucasiron viz., E. (C.) kapurkripalanorum Braasch 1983, E. (C.) papillatus Braasch, 2006a, E. (C.) psi Eaton 1883 which larva is described in details for the first time and E. (C.) suspicatus Braasch, 2006b . The subgeneric status of E. lahaulensis Kapur & Kripalani 1963 cannot be fixed due to non-availability of larval description. A dichotomous key to the larvae of available species in India is presented. Distribution of subgenera and species within India is discussed.
2. The Nature of Psychiatric Diagnoses
Authors: Hens Kristien
Published: June 2021

This chapter explores a first meaning of autism, that it is a psychiatric disorder defined in a diagnostic manual. We investigate what a psychiatric disorder is. I give an overview of philosophical discussions about the distinction between mind and brain, psychology and biology. I explain how biological explanations for mental disorders have the advantage that they can take away feelings of guilt and open up routes towards healing. At the same time I argue, using Karl Jasper’s distinction between understanding and explanation, that reductionist approaches that merely give a causal biological explanation of mental disorders neglect the importance of understanding the meaning and context in which phenomena occur.
6. Epistemic Injustice and Language
Authors: Hens Kristien
Published: June 2021

This chapter explores why it had taken a long time before people considered testimonials of autistic people as valuable input of information. I analyse this as an example of epistemic injustice. I also elaborate on what this means to incorporate experiences of those who cannot express themselves very well in words, such as autistic people who do not use verbal language or people with an intellectual disability. I argue that this does not mean that these testimonials should be valued less, but that it is the moral duty of researchers, clinicians and ethicists to actively search for ways to take seriously testimonials that are a bit harder to understand or collect.
7. Experiences of Autism
Authors: Hens Kristien , Langenberg Raymond
Published: June 2021

This chapter describes qualitative research of myself and others of the experiences of autistic persons. Such research demonstrates that autism is not solely a fixed identity that is persistent throughout one’s life. The diagnosis is a description of one’s functioning and can form the basis of how others understand you. As such, it is often a welcome explanation of the challenges people experience. But the meaning of autism and of the diagnosis of autism changes. There is the possibility for learning and misunderstanding in the interaction with others and the question of what it means to be autistic itself.
8. Interlude
Authors: Hens Kristien
Published: June 2021

This chapter offers some speculative reflections on autism and time. I describe autistic experiences of time in literature and in empirical research. Such experiences may be different from neurotypical experiences of time. However, this does not mean that autistic people are permanently out of sync with neurotypical people and vice versa. Respecting each other’s vulnerability is a question of adapting the own behaviour to accommodate the other and recognizing a joint base from which the other can be understood to help the other tackle challenges in such a way that they feel comfortable.
Prologue
Authors: Hens Kristien
Published: June 2021

This chapter introduces the major themes of the book. The first theme is that of the many meanings of autism. The second theme is the importance of experience in knowing a phenomenon such as autism. The third theme is looking dynamically at biology.
Frequency-Dependent Estimation of Effective Spatial Degrees of Freedom
Authors: Kunz Torben , Laepple Thomas
Published: June 2021

Climate variability occurs over wide ranges of spatial and temporal scales. It exhibits a complex spatial covariance structure, which depends on geographic location (e.g., tropics vs extratropics) and also consists of a superposition of (i) components with gradually decaying positive correlation functions and (ii) teleconnections that often involve anticorrelations. In addition, there are indications that the spatial covariance structure depends on frequency. Thus, a comprehensive assessment of the spatiotemporal covariance structure of climate variability would require an extensive set of statistical diagnostics. Therefore, it is often desirable to characterize the covariance structure by a simple summarizing metric that is easy to compute from datasets. Such summarizing metrics are useful, for example, in the context of comparisons between climate models or between models and observations. Here we introduce a frequency-dependent version of a simple measure of the effective spatial degrees of freedom. The measure is based on the temporal variance of the global average of some climate variable, and its novel aspect consists in its frequency dependence. We also provide a clear geometric interpretation of the measure. Its easy applicability is demonstrated using near-surface temperature and precipitation fields obtained from a paleoclimate model simulation. This application reveals a distinct scaling behavior of the spatial degrees of freedom as a function of frequency, ranging from monthly to millennial scales.
Impact of Temperature on Physical and Mental Health: Evidence from China
Authors: Yang Zhiming , Yang Bo , Liu Pengfei , Zhang Yunquan , Yuan Xiao-Chen
Published: June 2021

Climate may significantly affect human society. Few studies have focused on the temperature impact on residents’ health, especially mental health status. This paper uses 98 423 observations in China to study the relationship between temperature and health, based on the China Family Panel Studies survey during 2010–16. We analyze the health effects of extreme hot and cold weather and compare the effects under different social demographic factors including gender, age, and income. We find that temperature and health status exhibit a nonlinear relationship. Women and low-income households are more likely to be impacted by extreme cold, whereas men, the elderly, and high-income households are more sensitive to extreme heat. Our results highlight the potential effects of extreme temperatures on physical and mental health and provide implications for future policy decisions to protect human health under a changing climate.
Weather, Values, Capacity and Concern: Toward a Social-Cognitive Model of Specialty Crop Farmers’ Perceptions of Climate Change Risk
Authors: Han Guang , Schoolman Ethan D. , Arbuckle J. Gordon , Morton Lois Wright
Published: June 2021

As specialty crop production has become increasingly important to U.S. agriculture, public and private stakeholders have called for research and outreach efforts centered on risks posed by climate change. Drawing on a survey of specialty crop farmers, this study explores farmers’ perceptions of climate change risks. Underlying cognitive, experiential, and socio-cultural factors hypothesized to influence farmers’ climate change risk perceptions are tested using structural equation modeling techniques. Results show that specialty crop farmers exhibit an overall moderate concern about climatic risks. The more capable and prepared farmers feel themselves to be, the less concerned they are about climate change. Farmers who have recently experienced more extreme weather events perceive climate change to present greater risks. In addition, farmers’ risk perceptions are also shaped by attitudes toward human exemptionalism and productivism values. Based on these findings, we provide recommendations for outreach and future research.
Micromechanical modeling for the in-plane mechanical behavior of orthogonal three-dimensional woven ceramic matrix composites with transverse and matrix cracking
Authors: Onodera Sota , Tsuyuki Junpei , Okabe Tomonaga
Published: June 2021

Ceramic matrix composites (CMCs) are currently being considered for applications in the hot-section components of aviation gas turbines owing to their favorable characteristics. Herein, a micromechanical modeling is presented for orthogonal 3 D woven CMCs under in-plane loading. The three-dimensional effective compliance of the 3 D woven composite was derived using three-dimensional laminate theory and continuum damage mechanics. The damage variables were used to describe the stiffness reduction due to the transverse and matrix cracking in each fiber bundle. The calculation method for the transverse and matrix cracking evolutions under in-plane loading was established by introducing mixed-mode damage criteria. The stress redistribution among the fiber bundles of 3 D woven CMCs due to the fiber/matrix interfacial debonding around matrix cracking was considered to capture the interaction between the matrix and transverse crack evolutions. Additionally, a mesomechanical model comprising finite element analysis and damage mechanics was established to evaluate the stress perturbation due to the geometry of the woven structure. The edge face of the 3 D woven CMC was experimentally observed to measure the transverse and matrix cracks that occurred in each fiber bundle. The transverse and matrix crack densities predicted by the micromechanical and mesomechanical models reasonably agreed with the experimental results up to crack saturation. Furthermore, the micromechanical model reproduced the nonlinear stress–strain response under tensile and shear loading using mixed-mode damage criteria.
Meta-heuristic-based offloading task optimization in mobile edge computing
Authors: Abbas Aamir , Raza Ali , Aadil Farhan , Maqsood Muazzam
Published: June 2021

With the recent advancements in communication technologies, the realization of computation-intensive applications like virtual/augmented reality, face recognition, and real-time video processing becomes possible at mobile devices. These applications require intensive computations for real-time decision-making and better user experience. However, mobile devices and Internet of things have limited energy and computational power. Executing such computationally intensive tasks on edge devices either leads to high computation latency or high energy consumption. Recently, mobile edge computing has been evolved and used for offloading these complex tasks. In mobile edge computing, Internet of things devices send their tasks to edge servers, which in turn perform fast computation. However, many Internet of things devices and edge server put an upper limit on concurrent task execution. Moreover, executing a very small size task (1 KB) over an edge server causes increased energy consumption due to communication. Therefore, it is required to have an optimal selection for tasks offloading such that the response time and energy consumption will become minimum. In this article, we proposed an optimal selection of offloading tasks using well-known metaheuristics, ant colony optimization algorithm, whale optimization algorithm, and Grey wolf optimization algorithm using variant design of these algorithms according to our problem through mathematical modeling. Executing multiple tasks at the server tends to provide high response time that leads to overloading and put additional latency at task computation. We also graphically represent the tradeoff between energy and delay that, how both parameters are inversely proportional to each other, using values from simulation. Results show that Grey wolf optimization outperforms the others in terms of optimizing energy consumption and execution latency while selected optimal set of offloading tasks.
Autophagy receptors as viral targets
Authors: Ylä-Anttila Päivi
Published: June 2021

Activation of autophagy is part of the innate immune response during viral infections. Autophagy involves the sequestration of endogenous or foreign components from the cytosol within double-membraned vesicles and the delivery of their content to the lysosomes for degradation. As part of innate immune responses, this autophagic elimination of foreign components is selective and requires specialized cargo receptors that function as links between a tagged foreign component and the autophagic machinery. Pathogens have evolved ways to evade their autophagic degradation to promote their replication, and recent research has shown autophagic receptors to be an important and perhaps previously overlooked target of viral autophagy inhibition. This is a brief summary of the recent progress in knowledge of virus-host interaction in the context of autophagy receptors.
Effects of chiropractic spinal manipulation on laser-evoked pain and brain activity
Authors: Provencher Benjamin , Northon Stéphane , Gevers Montoro Carlos , O’Shaughnessy Julie , Piché Mathieu
Published: June 2021

The aim of this study was to examine the mechanisms underlying hypoalgesia induced by spinal manipulation (SM). Eighty-two healthy volunteers were assigned to one of the four intervention groups: no intervention, SM at T4 (homosegmental to pain), SM at T8 (heterosegmental to pain) or light mechanical stimulus at T4 (placebo). Eighty laser stimuli were applied on back skin at T4 to evoke pain and brain activity related to Aδ- and C-fibers activation. The intervention was performed after 40 stimuli. Laser pain was decreased by SM at T4 (p = 0.028) but not T8 (p = 0.13), compared with placebo. However, brain activity related to Aδ-fibers activation was not significantly modulated (all p > 0.05), while C-fiber activity could not be measured reliably. This indicates that SM produces segmental hypoalgesia through inhibition of nociceptive processes that are independent of Aδ fibers. It remains to be clarified whether the effect is mediated by the inhibition of C-fiber activity.
mLoc-mRNA: predicting multiple sub-cellular localization of mRNAs using random forest algorithm coupled with feature selection via elastic net
Authors: Meher Prabina Kumar , Rai Anil , Rao Atmakuri Ramakrishna
Published: June 2021

Background

Localization of messenger RNAs (mRNAs) plays a crucial role in the growth and development of cells. Particularly, it plays a major role in regulating spatio-temporal gene expression. The in situ hybridization is a promising experimental technique used to determine the localization of mRNAs but it is costly and laborious. It is also a known fact that a single mRNA can be present in more than one location, whereas the existing computational tools are capable of predicting only a single location for such mRNAs. Thus, the development of high-end computational tool is required for reliable and timely prediction of multiple subcellular locations of mRNAs. Hence, we develop the present computational model to predict the multiple localizations of mRNAs.

Results

The mRNA sequences from 9 different localizations were considered. Each sequence was first transformed to a numeric feature vector of size 5460, based on thek-mer features of sizes 1–6. Out of 5460 k-mer features, 1812 important features were selected by the Elastic Net statistical model. The Random Forest supervised learning algorithm was then employed for predicting the localizations with the selected features. Five-fold cross-validation accuracies of 70.87, 68.32, 68.36, 68.79, 96.46, 73.44, 70.94, 97.42 and 71.77% were obtained for the cytoplasm, cytosol, endoplasmic reticulum, exosome, mitochondrion, nucleus, pseudopodium, posterior and ribosome respectively. With an independent test set, accuracies of 65.33, 73.37, 75.86, 72.99, 94.26, 70.91, 65.53, 93.60 and 73.45% were obtained for the respective localizations. The developed approach also achieved higher accuracies than the existing localization prediction tools.

Conclusions

This study presents a novel computational tool for predicting the multiple localization of mRNAs. Based on the proposed approach, an online prediction server “mLoc-mRNA” is accessible athttp://cabgrid.res.in:8080/mlocmrna/. The developed approach is believed to supplement the existing tools and techniques for the localization prediction of mRNAs.
VISPR-online: a web-based interactive tool to visualize CRISPR screening experiments
Authors: Cui Yingbo , Wang Zihang , Köster Johannes , Liao Xiangke , Peng Shaoliang , Tang Tao , Huang Chun , Yang Canqun
Published: June 2021

Background

VISPR is an interactive visualization and analysis framework for CRISPR screening experiments. However, it only supports the output of MAGeCK, and requires installation and manual configuration. Furthermore, VISPR is designed to run on a single computer, and data sharing between collaborators is challenging.

Results

To make the tool easily accessible to the community, we present VISPR-online, a web-based general application allowing users to visualize, explore, and share CRISPR screening data online with a few simple steps. VISPR-online provides an exploration of screening results and visualization of read count changes. Apart from MAGeCK, VISPR-online supports two more popular CRISPR screening analysis tools: BAGEL and JACKS. It provides an interactive environment for exploring gene essentiality, viewing guide RNA (gRNA) locations, and allowing users to resume and share screening results.

Conclusions

VISPR-online allows users to visualize, explore and share CRISPR screening data online. It is freely available at http://vispr-online.weililab.org, while the source code is available at https://github.com/lemoncyb/VISPR-online.
PEPC of sugarcane regulated glutathione S-transferase and altered carbon–nitrogen metabolism under different N source concentrations in Oryza sativa
Authors: Lian Ling , Lin Yuelong , Wei Yidong , He Wei , Cai Qiuhua , Huang Wei , Zheng Yanmei , Xu Huibin , Wang Fuxiang , Zhu Yongsheng , Luo Xi , Xie Huaan , Zhang Jianfu
Published: June 2021

Background

Phosphoenolpyruvate carboxylase (PEPC) plays an important role in the primary metabolism of higher plants. Several studies have revealed the critical importance of PEPC in the interaction of carbon and nitrogen metabolism. However, the function mechanism of PEPC in nitrogen metabolism is unclear and needs further investigation.

Results

This study indicates that transgenic rice expressing the sugarcane C4-PEPC gene displayed shorter primary roots and fewer crown roots at the seedling stage. However, total nitrogen content was significantly higher in transgenic rice than in wild type (WT) plants. Proteomic analysis revealed that there were more differentially expressed proteins (DEPs) responding to nitrogen changes in transgenic rice. In particular, the most enriched pathway “glutathione (GSH) metabolism”, which mainly contains GSH S-transferase (GST), was identified in transgenic rice. The expression of endogenous PEPC, GST and several genes involved in the TCA cycle, glycolysis and nitrogen assimilation changed in transgenic rice. Correspondingly, the activity of enzymes including GST, citrate synthase, 6-phosphofructokinase, pyruvate kinase and ferredoxin-dependent glutamate synthase significantly changed. In addition, the levels of organic acids in the TCA cycle and carbohydrates including sucrose, starch and soluble sugar altered in transgenic rice under different nitrogen source concentrations. GSH that the substrate of GST and its components including glutamic acid, cysteine and glycine accumulated in transgenic rice. Moreover, the levels of phytohormones including indoleacetic acid (IAA), zeatin (ZT) and isopentenyladenosine (2ip) were lower in the roots of transgenic rice under total nutrients. Taken together, the phenotype, physiological and biochemical characteristics of transgenic rice expressing C4-PEPC were different from WT under different nitrogen levels.

Conclusions

Our results revealed the possibility that PEPC affects nitrogen metabolism through regulating GST, which provide a new direction and concepts for the further study of the PEPC functional mechanism in nitrogen metabolism.
Assessing the accuracy of ultrasound measurements of tracheal diameter: an in vitro experimental study
Authors: Ye Ran , Cai Feifei , Guo Chengnan , Zhang Xiaocheng , Yan Dan , Chen Chengshui , Chen Bin
Published: June 2021

Background

Recent studies indicate that ultrasound can detect changes in tracheal diameter during endotracheal tube (ETT) cuff inflation. We sought to assess the accuracy of ultrasound measurement of tracheal diameter, and to determine the relationship between tracheal wall pressure (TWP), cuff inflation volume (CIV), and the degree of tracheal deformation.

Methods

Our study comprised two parts: the first included 45 porcine tracheas, the second 41 porcine tracheas. Each trachea was intubated with a cuffed ETT, which was connected to an injector and the manometer via a three-way tap. The cuff was inflated and the cuff pressure recorded before and after intubation. The tracheal diameter was measured using ultrasound. This included three separate measurements: outer transverse diameter (OTD), internal transverse diameter (ITD), and anterior tracheal wall thicknesses (ATWT). A precision electronic Vernier caliper was also used to measure tracheal diameter. We calculated TWP and the percentage change of tracheal diameter. The Bland–Altman method, linear regression, and locally weighted regression (LOESS) were used to analyze the data.

Results

There were strong correlation and agreement for OTD (r = 0.97, P < 0.001) and ITD (r = 0.90, P < 0.001) as measured by ultrasound and by precision electronic Vernier caliper, but a poor correlation for ATWT (r = 0.58, P < 0.001). There was a strong correlation between the percentage change of OTD (OTD%, r = 0.75, P < 0.001) and CIV, the percentage change of ITD (ITD%, r = 0.77, P < 0.001) and CIV, TWP (r = 0.75, P < 0.001) and CIV. And a strong correlation was also found between TWP and OTD% (r = 0.84, P < 0.001), TWP and ITD% (r = 0.84, P < 0.001).

Conclusions

Use of ultrasound to measure OTD and ITD is accurate, but is less accurate for ATWT. There is a close correlation between OTD%, ITD%, CIV and TWP.
Psychometric properties of instruments to measure parenting practices and children’s movement behaviors in low-income families from Brazil
Authors: Goncalves Widjane Sheila Ferreira , Byrne Rebecca , de Lira Pedro Israel Cabral , Viana Marcelo Tavares , Trost Stewart G.
Published: June 2021

Background

Childhood obesity has increased remarkably in low and middle-income (LMIC) countries. Movement behaviors (physical activity, screen time, and sleep) are crucial in the development of overweight and obesity in young children. Yet, few studies have investigated the relationship between children’s movement behaviors and parenting practices because validated measures for use among families from LMIC are lacking. This study evaluated the psychometric properties of previously validated measures of young children’s physical activity, screen time, and sleep and parenting practices, translated and culturally adapted to Brazilian families.

Methods

A total of 78 parent-child dyads completed an interviewer-administered survey twice within 7 days. Child physical activity, sedentary time and sleep were concurrently measured using a wrist-worn accelerometer. Internal consistency and test-retest reliability was assessed using McDonald’s Omega and Intraclass Correlation Coefficients (ICC’s). Concurrent validity was evaluated by calculating Spearman correlations between parent reported child behaviors and accelerometer measured behaviors.

Results

Seventeen of the 19 parenting practices scales exhibited acceptable internal consistency reliability (Ω ≥ 0.70). Test-retest reliability ICC’s were acceptable and ranged from 0.82 - 0.99. Parent reported child physical activity was positively correlated with objectively measured total movement (rho= 0.29 - 0.46, p < .05) and energetic play (rho= 0.29 – 0.40, p < .05). Parent reported child screen time was positively correlated with objectively measured sedentary time; (rho = 0.26, p < .05), and inversely correlated with total movement (rho = - 0.39 – - 0.41, p < .05) and energetic play (rho = - 0.37 – - 0.41, p < .05). Parent reported night-time sleep duration was significantly correlated with accelerometer measured sleep duration on weekdays (rho = 0.29, p < .05), but not weekends.

Conclusions

Measurement tools to assess children’s movement behaviors and parenting practices, translated and culturally adapted for use in Brazilian families, exhibited acceptable evidence of concurrent validity, internal consistency, and test-retest reliability.
Evaluation of intermediate care for knee and hip osteoarthritis: a mixed-methods study
Authors: Arslan Ilgin G. , Voorbrood Vincent M. I. , Stitzinger Saskia A. G. , van de Kerkhove Maarten-Paul , Rozendaal Rianne M. , van Middelkoop Marienke , Bindels Patrick J. E. , Bierma-Zeinstra Sita M. A. , Schiphof Dieuwke
Published: June 2021

Background

To evaluate intermediate care for knee and hip osteoarthritis (KHOA) in the general practice that incorporate specialist services into general practice to prevent unnecessary referrals to hospitals.

Methods

We used a mixed methods approach including semi-structured interviews, patient experience questionnaires and data from medical records from three intermediate care projects. Semi-structured interviews were conducted with patients, general practitioners (GPs), orthopaedists and a healthcare manager in intermediate care. Satisfaction of patients who received intermediate care (n = 100) was collected using questionnaires. Referral data and healthcare consumption from medical records were collected retrospectively from KHOA patients before (n = 96) and after (n = 208) the implementation of intermediate care.

Results

GPs and orthopaedists in intermediate care experienced more intensive collaboration compared to regular care. This led to a perceived increase in GPs’ knowledge enabling better selection of referrals to orthopaedics and less healthcare consumption. Orthopaedists felt a higher workload and limited access to diagnostic facilities. Patients were satisfied and experienced better access to specialists’ knowledge in a trusted environment compared to regular care. Referrals to physiotherapy increased significantly after the implementation of intermediate care (absolute difference = 15%; 95% CI = 7.19 to 22.8), but not significantly to orthopaedics (absolute difference = 5.9%; 95% CI = -6.18 to 17.9).

Conclusions

Orthopaedists and GPs perceived the benefits of an intensified collaboration in intermediate care. Intermediate care may contribute to high quality of care through more physiotherapy referrals. Further research with longer follow-up is needed to confirm these findings and give more insight in referrals and healthcare consumption.
Biliary peritonitis due to liver cyst rupture in autosomal dominant polycystic kidney disease
Authors: Matsuo Hiroshi , Katayama Kan , Hayasaki Aoi , Iizawa Yusuke , Endo Mayumi , Murata Tomohiro , Mizuno Shugo , Dohi Kaoru
Published: June 2021

Background

Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent genetic kidney disease and polycystic liver disease is its major extrarenal manifestation, however biliary peritonitis due to a liver cyst rupture is extremely rare.

Case presentation

The patient was a 71-year-old Japanese woman who was diagnosed with ADPKD 3 years previously and developed right abdominal pain suddenly 1 month previously. As abdominal computed tomography (CT) showed a ruptured liver cyst in the right lobe, she was admitted to our hospital. Her symptoms improved with conservative management and she was discharged from the hospital after 1 week. Although she was asymptomatic for a while, she noticed abdominal distension and general malaise at 1 month after hospital discharge. Since abdominal CT showed massive ascites, she was admitted to our hospital again. A physical examination revealed abdominal distention without tenderness. Her serum creatinine, alkaline phosphatase, γ-glutamyl transpeptidase, total bilirubin, and CA19-9 were elevated. Abdominal paracentesis revealed amber transparent ascites and the bilirubin and CA19-9 concentrations were high. She was diagnosed with biliary peritonitis due to a ruptured liver cyst. Hemodialysis treatment was initiated with drainage of the ascites. The outflow of the ascites was no tendency to decrease and drip infusion cholangiography (DIC)-CT revealed a communication between the ruptured cyst and an intrahepatic bile duct. On day 31, she was transferred to a university hospital and abdominal surgery was performed. After removing the necrotic roof of the ruptured cyst on the right liver lobe, the orifice of the bile leakage was sutured. Cholecystectomy was performed and cholangiography showed no stones in the common bile duct. Abdominal CT one month after the operation showed no recurrence of ascites and she was discharged on day 49. Hemodialysis treatment was discontinued immediately after discharge because urine volume increased and her creatinine level decreased. There has been no recurrence of ascites since then.

Conclusions

While rare, biliary peritonitis can occur in association with the rupture of a liver cyst in ADPKD patients due to communication between the cyst and the intrahepatic bile duct, and DIC-CT should be recommended when biliary cyst rupture is suspected.
Quantitative assessments of pupillary light reflexes in hospital-onset unresponsiveness
Authors: Lee Hyunjo , Choi Soh Hyun , Park Bobin , Hong Yoon-Hee , Lee Han-Bin , Jeon Sang-Beom
Published: June 2021

Background

Patients who develop hospital-onset unresponsiveness should be promptly managed in order to avoid clinical deterioration. Pupillary examination through pupillary light reflex is the gold standard method in the initial evaluation of unresponsive patients. However, the current method of shining light and subjective description often shows poor reliability. The objective of this study is to explore whether a quantitative measurement of pupillary light reflexes is useful in detecting brain herniation syndrome and predicting neurological outcomes in patients who developed hospital-onset unresponsiveness after admission for non-neurological reasons.

Methods

This was a registry-based observational study on patients who activated the neurological rapid response team at Asan Medical Center (Seoul, Korea). Hospital-onset unresponsiveness was defined as a newly developed unresponsive state as assessed by the ACDU (Alert, Confused, Drowsy, and Unresponsive) scale during the hospital stay. Demographics, comorbidities, pupillometry parameters including Neurological Pupil index, brain herniation syndrome, in-hospital mortality, and modified Rankin Scale at 3-months were analyzed.

Results

In 214 consecutive patients with hospital-onset unresponsiveness, 37 (17%) had brain herniation syndrome. The optimal cut-off value of Neurological Pupil index for detecting brain herniation syndrome was < 1.6 (specificity, 91% [95% confidence interval (CI) = 86–95]; sensitivity, 49% [95% CI = 32–66]). The in-hospital mortality rate was 28% (59/214); the Neurological Pupil index was negatively associated with in-hospital mortality after adjustments for the presence of brain herniation syndrome (adjusted odds ratio = 0.77, 95% CI = 0.62–0.96). Poor neurological outcomes (modified Rankin Scale ≥4) at 3 months was observed in 76% (152/201) of the patients; the Neurological Pupil index was negatively associated with poor neurological outcomes after adjustments for clinical variables (adjusted odds ratio = 0.67, 95% CI = 0.49–0.90).

Conclusions

Quantitative measurements of pupillary light reflexes may be useful for early detection of potentially life-threatening neurological conditions in patients with hospital-onset unresponsiveness.
Next-generation sequencing combined with serological tests based pathogen analysis for a neurocysticercosis patient with a 20-year history:a case report
Authors: Chen Bin , Chen Zheng , Yang Yi-shu , Cai Gui-lan , Xu Xiao-jiao , Guan Hong-zhi , Ren Hai-tao , Tuo Hou-zhen
Published: June 2021

Background

Neurocysticercosis (NCC) is the most common helminthic infection of the central nervous system (CNS) caused by the larval stage of Taenia solium. Accurate and early diagnosis of NCC remains challenging due to its heterogeneous clinical manifestations, neuroimaging deficits, variable sensitivity, and specificity of serological tests. Next-generation sequencing (NGS)-based pathogen analysis in patient’s cerebrospinal fluid (CSF) with NCC infection has recently been reported indicating its diagnostic efficacy. In this case study, we report the diagnosis of a NCC patient with a symptomatic history of over 20 years using NGS analysis and further confirmation of the pathology by immunological tests.

Case presentation

This study reports the clinical imaging and immunological features of a patient with a recurrent headache for more than 20 years, which worsened gradually with the symptom of fever for more than 7 years and paroxysmal amaurosis for more than 1 year. By utilizing NGS technique, the pathogen was detected in patient’s CSF, and the presence of Taenia solium-DNA was confirmed by a positive immunological reaction to cysticercus IgG antibody in CSF and serum samples. The symptoms of the patient were alleviated, and the CSF condition was improved substantially after the anti-helminthic treatment.

Conclusions

This study suggests that combining CSF NGS with cysticercus IgG testing may be a highly promising approach for diagnosing the challenging cases of NCC. Further studies are needed to evaluate the parasitic DNA load in patients’ CSF for the diagnosis of disease severity, stage, and monitoring of therapeutic responses.
Efficacy and safety of pulsed radiofrequency modulation of thoracic dorsal root ganglion or intercostal nerve on postherpetic neuralgia in aged patients: a retrospective study
Authors: Huang Xuehua , Ma Yanfeng , Wang Weimin , Guo Yunxiu , Xu Bo , Ma Ke
Published: June 2021

Background

Postherpetic neuralgia (PHN) is common in elderly patients and can be alleviated by pulsed radiofrequency (PRF). However, PRF treatments display different efficacy on different nerves. The purpose of this study was to evaluate the efficacy and safety of ultrasound-guided PRF modulation on thoracic dorsal root ganglion (DRG) or intercostal nerve (ICN) for PHN in aged patients and to provide a theoretical basis for clinical treatment.

Methods

We classified aged patients into two groups, DRG group and ICN group, based on the needle tip position. Visual analogue scale (VAS) and concise health status questionnaire (Short-form 36 health/survey questionnaire, SF-36) were used to evaluate the pain intensity and the life quality of the patients before and 2, 4 and 12 weeks after the PRF treatments. We also recorded the adverse reactions during the treatments.

Results

After the PRF treatment, the scores of VAS and SF-36 (assessing general health perception, social function, emotional role, mental health, and pain) improved significantly in both groups (P < 0.05). The mean VAS score in the DRG group was significantly lower than that in the ICN group 2 weeks after treatment, and remained for 12 weeks. The SF-36 scores in the DRG group were significantly higher than those in the ICN group (P < 0.05). We found a similar incidence of adverse reactions between the two groups (P > 0.05).

Conclusions

PRF therapy is safe and effective for elderly patients with postherpetic neuralgia. However, PRF treatment in dorsal root ganglion is superior to that in intercostal nerve with improving VAS and SF-36 scores to a greater extent in older patients.

Trial registration

ChiCTR2100044176.