bluuebunny/crossref_metadata_2025_split huggingface dataset:
Augmentative and alternative communication intervention for in-patient individuals with post-stroke aphasia: study protocol of a parallel-group, pragmatic randomized controlled trial
Authors: Huang Li , Chen Szu-Han Kay , Xu Shutian , Wang Yongli , Jin Xing , Wan Ping , Sun Jikang , Tao Jiming , Zhang Sicong , Zhang Guohui , Shan Chunlei 
Published: November 2021

Abstract
Background
People with post-stroke aphasia commonly receive speech-language therapy (SLT) when they are admitted to hospitals. Commonly, these patients reported communication difficulties in in-patient settings. Augmentative and alternative communication (AAC) has been reported as an effective treatment approach to improve communication effectiveness, language performance, decreasing depression, and improving quality of life for this population. However, little evidence has demonstrated the use of AAC intervention (AACT) in early recovery from people with post-stroke aphasia in in-patient rehabilitation settings for improving these patients’ communication effectiveness. The pilot randomized controlled trial (RCT) will explore the effectiveness and feasibility of including AACT in regular SLT for in-patient people with post-stroke aphasia.

Method
This pilot RCT is a single-blind, randomized controlled trial with two parallel groups. Both groups receive a 1-h treatment session, including either both AACT and SLT or SLT only for ten consecutive days. We aim to include 22 in-patient participants with post-stroke aphasia in each group. Participants will be assessed at pre- and post-intervention and 2 weeks after intervention. The primary outcomes are the ability of communication measured by the communication of basic needs subtest in the Functional Assessment of Communication Skills for Adult (FACS) and the overall language performance measured by the Chinese Standard Aphasia Battery (ABC). The secondary outcomes include a 10-min conversation, the 10-item Hospital version of the Stroke Aphasic Depression Questionnaire (SADQH-10), the Stroke-Specific Quality of Life Scale (SS-QOL), and a patient and caregiver satisfaction questionnaire.

Discussion
This pilot RCT will contribute to new scientific evidence to the field of aphasia rehabilitation in early recovery during the in-patient period. The paper describes the trial, which will explore the effect of combining AACT and SLT and SLT only, our choice of primary and secondary outcome measures, and proposed analyses. The study results will provide information for implementing AACT in the regular in-patient SLT of future RCTs.

Trial registration
Chinese Clinical Trial Registry database (ChiCTR) ChiCTR2000028870. Registered on 5 January 2020
The ACAMTO study—impact of add-on osteopathic treatment on adolescent patients with anorexia nervosa: study protocol for a randomized controlled trial
Authors: Letranchant Aurélie , Montebello Yunkyung Kim-de , bigre Corinne Dugré-Le , Wagner Agathe , Curt Florence , Silva Jérôme , Nicolas Isabelle , Votadoro Pablo , Kalindjian Nina , Korchonnoff Anna , Gutierre Andréa , Novelli Ana Beatriz , Pham-Scottez Alexandra , Corcos Maurice 
Published: November 2021

Abstract
Background
Anorexia nervosa (AN) mainly affects women (sex ratio 1/10) and most often starts during adolescence. The prognosis of AN remains poor (10% of deaths and high risk of chronicity). Body dissatisfaction, disturbances in recognition and identification of body sensations are some of the key symptoms of AN. However, there is a contrast between this consensual observation of body image disorders in AN, and the relative deficit of specifically targeted body treatments. Our proposal for a body approach specifically dedicated to AN is based on the understanding that posture, breathing, muscle tension and body perception are closely linked to our psychological and emotional state and are therefore disturbed in patients with AN. The purpose of this monocentric randomized controlled trial is to evaluate if a targeted osteopathic protocol treatment for AN in addition to treatment as usual (TAU) is significantly more effective than TAU alone.

Methods
In total, 72 patients meeting the inclusion criteria will be randomly assigned to one of the two treatment groups: one receiving the specific osteopathic treatment targeted for AN in addition to the TAU (group A) and the other one, receiving TAU only (group B). The patients in group A will receive 5 30-min osteopathic treatment sessions. Soft specific palpatory techniques on the diaphragm, digestive system and cervical region will be performed. The TAU is defined by the multidisciplinary approach recommended by the French health high authority. The primary outcome is the evaluation of interoceptive sensibility and secondary outcomes include clinical and psychopathology-related symptoms with assessment of somatic dysfunctions’ evolution. A qualitative study will also be carried out, applying the Interpretative Phenomenological Analysis method. Patients will be included for a maximum of 14 weeks between the inclusion time and the last evaluation.

Discussion
If the results of the study are positive (statistically significant efficacy of this osteopathic treatment protocol), the study will provide arguments in favor of osteopathic sessions as a possible non-invasive additional treatment option in the multidisciplinary care approach for patients with AN.

Trial registration
ClinicalTrials.gov ID: NCT04666415, Release Date: December 11, 2020; N° ID-RCB: 2019-A02613-54.
Genetic diversity and immunogenicity of the merozoite surface protein 1 C-terminal 19-kDa fragment of Plasmodium ovale imported from Africa into China
Authors: Xu Qinwen , Liu Sihong , Kassegne Kokouvi , Yang Bo , Lu Jiachen , Sun Yifan , Zhong Wenli , Zhang Miaosa , Liu Yaobao , Zhu Guoding , Cao Jun , Cheng Yang 
Published: November 2021

Abstract
Background
Merozoite surface protein 1 (MSP1) plays an essential role in erythrocyte invasion by malaria parasites. The C-terminal 19-kDa region of MSP1 has long been considered one of the major candidate antigens for a malaria blood-stage vaccine against Plasmodium falciparum. However, there is limited information on the C-terminal 19-kDa region of Plasmodium ovale MSP1 (PoMSP119). This study aims to analyze the genetic diversity and immunogenicity of PoMSP119.

Methods
A total of 37 clinical Plasmodium ovale isolates including Plasmodium ovale curtisi and Plasmodium ovale wallikeri imported from Africa into China and collected during the period 2012–2016 were used. Genomic DNA was used to amplify P. ovale curtisi (poc) msp119 (pocmsp119) and P. ovale wallikeri (pow) msp119 (powmsp119) genes by polymerase chain reaction. The genetic diversity of pomsp119 was analyzed using the GeneDoc version 6 programs. Recombinant PoMSP119 (rPoMSP119)-glutathione S-transferase (GST) proteins were expressed in an Escherichia coli expression system and analyzed by western blot. Immune responses in BALB/c mice immunized with rPoMSP119-GST were determined using enzyme-linked immunosorbent assay. In addition, antigen-specific T cell responses were assessed by lymphocyte proliferation assays. A total of 49 serum samples from healthy individuals and individuals infected with P. ovale were used for the evaluation of natural immune responses by using protein microarrays.

Results
Sequences of pomsp119 were found to be thoroughly conserved in all the clinical isolates. rPoMSP119 proteins were efficiently expressed and purified as ~ 37-kDa proteins. High antibody responses in mice immunized with rPoMSP119-GST were observed. rPoMSP119-GST induced high avidity indexes, with an average of 92.57% and 85.32% for rPocMSP119 and rPowMSP119, respectively. Cross-reactivity between rPocMSP119 and rPowMSP119 was observed. Cellular immune responses to rPocMSP119 (69.51%) and rPowMSP119 (52.17%) induced in rPocMSP119- and rPowMSP119-immunized mice were found in the splenocyte proliferation assays. The sensitivity and specificity of rPoMSP119-GST proteins for the detection of natural immune responses in patients infected with P. ovale were 89.96% and 75%, respectively.

Conclusions
This study revealed highly conserved gene sequences of pomsp119. In addition, naturally acquired humoral immune responses against rPoMSP1 were observed in P. ovale infections, and high immunogenicity of rPoMSP119 in mice was also identified. These instructive findings should encourage further testing of PoMSP119 for rational vaccine design.

Graphical abstract
Functional characterization of two clip domain serine proteases in innate immune responses of Aedes aegypti
Authors: Wang Hao-Cheng , Wang Qiu-Hui , Bhowmick Biswajit , Li Yi-Xun , Han Qian 
Published: November 2021

AbstractBackgroundClip domain serine proteases (CLIPs), a very diverse group of proteolytic enzymes, play a crucial role in the innate immunity of insects. Innate immune responses are the first line of defense in mosquitoes against the invasion of pathogenic microorganisms. The Toll pathway, immunodeficiency (IMD) pathway and melanization are the main processes of innate immunity inAedes aegypti. CLIPS are classified into five subfamilies—CLIPA, CLIPB, CLIPC, CLIPD, and CLIPE—based on their sequence specificity and phylogenetic relationships. We report the functional characterization of the genes that code for two CLIPs inAe. aegypti(Ae):Ae-CLIPB15andAe-CLIPB22.MethodsClustal Omega was used for multiple amino acid sequence alignment ofAe-CLIPB15andAe-CLIPB22with differentCLIPgenes from other insect species. The spatiotemporal expression profiles ofAe-CLIPB15andAe-CLIPB22were examined. We determined whetherAe-CLIPB15andAe-CLIPB22respond to microbial challenge and tissue injury. RNA interference (RNAi) was used to explore the function ofAe-CLIPB15andAe-CLIPB22in the defense ofAe. aegyptiagainst bacterial and fungal infections. The expression levels of nuclear factor kappa B (NF-κB) transcription factorsREL1andREL2in the Toll pathway and IMD pathway after bacterial infection were investigated. Finally, the change in phenoloxidase (PO) activity inAe-CLIPB15andAe-CLIPB22knockdown adults was investigated.ResultsWe performed spatiotemporal gene expression profiling ofAe-CLIPB15andAe-CLIPB22genes inAe.aegyptiusing quantitative real-time polymerase chain reaction. These genes were expressed in different stages and tissues. The messenger RNA (mRNA) levels for both genes were also up-regulated by Gram-negative bacteriaEscherichia coli, Gram-positive bacteriaStaphylococcus aureusand fungalBeauveria bassianainfections, as well as in the tissue injury experiments. RNAi-mediated knockdown ofAe-CLIPB15led to a significant decrease of PO activity in the hemolymph ofAe. aegypti, while other RNAi experiments revealed that bothAe-CLIPB15andAe-CLIPB22were involved in immune defense against bacterial and fungal infections. The mRNA expression of NF-κB transcription factorsREL1andREL2in the Toll pathway and IMD pathway differed betweenAe-CLIPB15andAe-CLIPB22knockdown mosquitoes infected with bacteria and wild type mosquitoes infected with bacteria.ConclusionsOur findings suggest thatAe-CLIPB15andAe-CLIPB22play a critical role in mosquito innate immunity, and that they are involved in immune responses to injury and infection. Their regulation of transcription factors and PO activity indicates that they also play a specific role in the regulation of innate immunity.Graphical Abstract
Development of a chemogenomics library for phenotypic screening
Authors: Dafniet Bryan , Cerisier Natacha , Boezio Batiste , Clary Anaelle , Ducrot Pierre , Dorval Thierry , Gohier Arnaud , Brown David , Audouze Karine , Taboureau Olivier 
Published: November 2021

AbstractWith the development of advanced technologies in cell-based phenotypic screening, phenotypic drug discovery (PDD) strategies have re-emerged as promising approaches in the identification and development of novel and safe drugs. However, phenotypic screening does not rely on knowledge of specific drug targets and needs to be combined with chemical biology approaches to identify therapeutic targets and mechanisms of actions induced by drugs and associated with an observable phenotype. In this study, we developed a system pharmacology network integrating drug-target-pathway-disease relationships as well as morphological profile from an existing high content imaging-based high-throughput phenotypic profiling assay known as “Cell Painting”. Furthermore, from this network, a chemogenomic library of 5000 small molecules that represent a large and diverse panel of drug targets involved in diverse biological effects and diseases has been developed. Such a platform and a chemogenomic library could assist in the target identification and mechanism deconvolution of some phenotypic assays. The usefulness of the platform is illustrated through examples.
Alpha-synuclein from patient Lewy bodies exhibits distinct pathological activity that can be propagated in vitro
Authors: Marotta Nicholas P. , Ara Jahan , Uemura Norihito , Lougee Marshall G. , Meymand Emily S. , Zhang Bin , Petersson E. James , Trojanowski John Q. , Lee Virginia M.-Y. 
Published: November 2021

AbstractLewy bodies (LBs) are complex, intracellular inclusions that are common pathological features of many neurodegenerative diseases. They consist largely of aggregated forms of the protein alpha-Synuclein (α-Syn), which misfolds to give rise to beta-sheet rich amyloid fibrils. The aggregation of monomers into fibrils occurs readily in vitro and pre-formed fibrils (PFFs) generated from recombinant α-Syn monomers are the basis of many models of LB diseases. These α-Syn PFFs recapitulate many pathological phenotypes in both cultured cells and animal models including the formation of α-Syn rich, insoluble aggregates, neuron loss, and motor deficits. However, it is not clear how closely α-Syn PFFs recapitulate the biological behavior of LB aggregates isolated directly from patients. Direct interrogation of the cellular response to LB-derived α-Syn has thus far been limited. Here we demonstrate that α-Syn aggregates derived from LB disease patients induce pathology characterized by a prevalence of large somatic inclusions that is distinct from the primarily neuritic pathology induced by α-Syn PFFs in our cultured neuron model. Moreover, these LB-derived aggregates can be amplified in vitro using recombinant α-Syn to generate aggregates that maintain the unique, somatic pathological phenotype of the original material. Amplified LB aggregates also showed greater uptake in cultured neurons and greater pathological burden and more rapid pathological spread in injected mouse brains, compared to α-Syn PFFs. Our work indicates that LB-derived α-Syn from diseased brains represents a distinct conformation species with unique biological activities that has not been previously observed in fully recombinant α-Syn aggregates and demonstrate a new strategy for improving upon α-Syn PFF models of synucleinopathies using amplified LBs.
Assembly of α-synuclein and neurodegeneration in the central nervous system of heterozygous M83 mice following the peripheral administration of α-synuclein seeds
Authors: Macdonald Jennifer A. , Chen John L. , Masuda-Suzukake Masami , Schweighauser Manuel , Jaunmuktane Zane , Warner Thomas , Holton Janice L. , Grossman Annabelle , Berks Richard , Lavenir Isabelle , Goedert Michel 
Published: November 2021

AbstractPeripheral administration (oral, intranasal, intraperitoneal, intravenous) of assembled A53T α-synuclein induced synucleinopathy in heterozygous mice transgenic for human mutant A53T α-synuclein (line M83). The same was the case when cerebellar extracts from a case of multiple system atrophy with type II α-synuclein filaments were administered intraperitoneally, intravenously or intramuscularly. We observed abundant immunoreactivity for pS129 α-synuclein in nerve cells and severe motor impairment, resulting in hindlimb paralysis and shortened lifespan. Filaments immunoreactive for pS129 α-synuclein were in evidence. A 70% loss of motor neurons was present five months after an intraperitoneal injection of assembled A53T α-synuclein or cerebellar extract with type II α-synuclein filaments from an individual with a neuropathologically confirmed diagnosis of multiple system atrophy. Microglial cells changed from a predominantly ramified to a dystrophic appearance. Taken together, these findings establish a close relationship between the formation of α-synuclein inclusions in nerve cells and neurodegeneration, accompanied by a shift in microglial cell morphology. Propagation of α-synuclein inclusions depended on the characteristics of both seeds and transgenically expressed protein.
No patella resurfacing total knee arthroplasty leads to reduction in the thickness of patellar cartilage to less than half within 5 years: a quantitative longitudinal evaluation using MRI
Authors: Sato Dai , Inoue Masayuki , Sasaki Takuro , Uchida Jun , Onodera Tomohiro , Kondo Eiji , Iwasaki Norimasa 
Published: November 2021

AbstractPurposePatellar resurfacing in total knee arthroplasty (TKA) remains controversial as recent meta-analyses have not shown its clear superiority; however, most authors recommend it because it is associated with less frequent anterior knee pain and need for reoperation. We aimed to clarify the changes in patellar cartilage thickness in no patellar resurfacing TKA using a ceramic femoral component on magnetic resonance imaging (MRI).MethodsBetween 2009 and 2014, 40 consecutive patients (59 knees) were included in this study. All patients underwent TKA using zirconia ceramic femoral implants without patellar resurfacing. Indications for no patellar resurfacing TKA were absence of anterior knee pain, patellar compression pain, and osteoarthritic changes in the patellofemoral joint on plain radiography. The mean postoperative follow-up duration was 81.5 months (range, 25–131 months). Clinical and radiological evaluations were performed preoperatively and 5 years after TKA. Patellar cartilage thickness was evaluated preoperatively and every year for 5 years after TKA using MRI T2-weighted imaging. The patellar cartilage was divided into three regions of interest: medial, central, and lateral. To standardise the variation in patellar thickness among patients, the percent cartilage thickness was calculated.ResultsThe implant’s position was appropriate in all cases. Compared to preoperative scores, 5 years postoperatively, the Japanese Orthopedic Association score and Oxford knee score significantly improved from 52.1 to 84.7; mean tilting angle and congruence angle did not change significantly; mean lateral shift ratio significantly increased from 7.1% to 14.6%; cartilage thickness significantly decreased (P < 0.05); and the percentage cartilage thickness of the central, medial, and lateral cartilage zones gradually thinned to less than half. Four patients underwent conversion to patellar resurfacing due to anterior knee pain, without loosening the femoral and tibial implants.ConclusionThe patellar cartilage thickness decreased to less than half its preoperative level within 5 years after no patellar resurfacing TKA; this would led to clinical problems and conversion to patellar resurfacing.Level of evidenceLevel III.
Effects of therapeutic plasma exchange on the endothelial glycocalyx in septic shock
Authors: Stahl Klaus , Hillebrand Uta Carola , Kiyan Yulia , Seeliger Benjamin , Schmidt Julius J. , Schenk Heiko , Pape Thorben , Schmidt Bernhard M. W. , Welte Tobias , Hoeper Marius M. , Sauer Agnes , Wygrecka Malgorzata , Bode Christian , Wedemeyer Heiner , Haller Hermann , David Sascha 
Published: November 2021

Abstract
Background
Disruption of the endothelial glycocalyx (eGC) is observed in septic patients and its injury is associated with multiple-organ failure and inferior outcomes. Besides this biomarker function, increased blood concentrations of shedded eGC constituents might play a mechanistic role in septic organ failure. We hypothesized that therapeutic plasma exchange (TPE) using fresh frozen plasma might influence eGC-related pathology by removing injurious mediators of eGC breakdown while at the time replacing eGC protective factors.

Methods
We enrolled 20 norepinephrine-dependent (NE > 0.4 μg/kg/min) patients with early septic shock (onset < 12 h). Sublingual assessment of the eGC via sublingual sidestream darkfield (SDF) imaging was performed. Plasma eGC degradation products, such as heparan sulfate (HS) and the eGC-regulating enzymes, heparanase (Hpa)-1 and Hpa-2, were obtained before and after TPE. A 3D microfluidic flow assay was performed to examine the effect of TPE on eGC ex vivo. Results were compared to healthy controls.

Results
SDF demonstrated a decrease in eGC thickness in septic patients compared to healthy individuals (p = 0.001). Circulating HS levels were increased more than sixfold compared to controls and decreased significantly following TPE [controls: 16.9 (8–18.6) vs. septic patients before TPE: 105.8 (30.8–143.4) μg/ml, p < 0.001; vs. after TPE: 70.7 (36.9–109.5) μg/ml, p < 0.001]. The Hpa-2 /Hpa-1 ratio was reduced in septic patients before TPE but normalized after TPE [controls: 13.6 (6.2–21.2) vs. septic patients at inclusion: 2.9 (2.1–5.7), p = 0.001; vs. septic patients after TPE: 13.2 (11.2–31.8), p < 0.001]. Ex vivo stimulation of endothelial cells with serum from a septic patient induced eGC damage that could be attenuated with serum from the same patient following TPE.

Conclusions
Septic shock results in profound degradation of the eGC and an acquired deficiency of the protective regulator Hpa-2. TPE removed potentially injurious eGC degradation products and partially attenuated Hpa-2 deficiency.
Trial registration clinicaltrials.gov NCT04231994, retrospectively registered 18 January 2020
Changes in surface water masses in the northern East China Sea since the Last Glacial Maximum based on diatom assemblages
Authors: Shirota Keiko , Okazaki Yusuke , Konno Susumu , Miyairi Yosuke , Yokoyama Yusuke , Kubota Yoshimi 
Published: November 2021

AbstractWe investigated diatom assemblages for the last 19 ka in a piston core KY07-04 PC01 collected from the northern Okinawa Trough, East China Sea. Most of the diatom taxa in the Core KY07-04 PC01 were subtropical to temperate marine species throughout the core. Pronounced turnover of major diatom groups from periphytic to planktonic taxa occurred during deglaciation between 17 and 14 ka ago. During the Last Glacial Maximum (LGM) to early deglaciation, the representative taxa were Paralia spp., a periphytic diatom abundant in continental shelves of the modern East China Sea covering the Chinese Coastal Water. Relative abundances of Paralia spp. rapidly decreased during 15–14 ka ago, corresponding to sea-level rise, displaced by planktonic taxa such as Thalassionema. Thalassionema nitzschioides varieties living in subtropical water increased since 12 ka and have reached the present level at 8 ka ago, suggesting strengthening the influences of Kuroshio water in the northern East China Sea during the early to middle Holocene. Warm planktonic diatom taxa such as Nitzschia bicapitata also gradually increased from 12 to 8 ka ago. Near the core top, a sudden increase in N. bicapitata might relate to the intensifying Kuroshio during the latest Holocene.