bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Physical Therapy Dosage on Functional Recovery Following TBI
Authors: Tolland Joseph , Miccile Lauren A. , Burke Katherine 
Published: December 2019

Background/Purpose:
Evidence supporting neurorehabilitation dosage after traumatic brain injury is limited. High-dose, high-intensity intervention, involving maximal frequency, time, and patient participation, facilitates neuroplasticity and optimizes outcomes. This patient made significant functional progress with the dosage of therapy provided, warranting investigation into the optimal dosage of therapy in this patient population.

Case Description:
A 27-year-old man with severe, traumatic brain injury defined by the Glasgow Coma Scale received physical therapy in an acute care hospital within a large academic medical center. Due to insurance complications, he was unable to be discharged to an inpatient rehabilitation facility. He remained in the hospital receiving physical therapy until he was safe to be discharged home.

Intervention:
The patient received an average of 16 minutes of physical therapy, 4 times/week, totaling 320 minutes over 35 additional days spent in the acute hospital setting. Treatment focused on progressing functional mobility, preventing complications, and task-specific functional training.

Outcomes:
The patient received a 79% lower dosage of physical therapy than expected based on standard requirements at an acute rehabilitation facility. The patient progressed from actively performing less than 25% of functional tasks to performing 100% of functional tasks with supervision for safety. He ambulated with supervision and negotiated stairs with contact guard assistance at time of discharge.

Discussion:
The patient made significant functional gains. This raises the question of optimal dosage of rehabilitation following traumatic brain injury. We challenge therapists to consider that the optimal dose of rehabilitation in the acute care setting remains unknown and further investigation is needed.
Hearing Recovery After Ejection of Air in a Case of Traumatic Pneumolabyrinth: Mechanism and Management Options
Authors: Oda Kiyoshi , Yamamoto Hiroki , Kobayashi Toshimitsu , Hidaka Hiroshi , Ikeda Ryoukichi , Yoshida Naohiro 
Published: December 2019

Objective:
To describe a case of traumatic pneumolabyrinth and subsequent hearing recovery after ejection of air with transcanal endoscopic surgical exploration.

Patients:
A 38-year-old man was struck by his child while cleaning his ear with an ear pick made of bamboo, which penetrated deep into the left ear canal. Severe vertigo with vomiting and left hearing impairment ensued. In addition, high-resolution computed tomography demonstrated an air density within the vestibule.

Interventions:
Exploratory tympanotomy was performed endoscopically a day after the injury and air was ejected from the oval window surgically.

Main Outcome Measures:
High-resolution computed tomography, audiologic testing.

Results:
Several hours after surgery, the patient's subjective vestibular symptoms lessened and 7 days after surgery, the patient felt slight dizziness when moving his head and no apparent spontaneous nystagmus was observed with an infrared charge-coupled device camera and was discharged from the hospital. Two years later, there are no subjective vestibular symptoms at all and the pure-tone average of his left ear improved to 16.7 dB.

Conclusion:
We presented a case of traumatic pneumolabyrinth and the subsequent hearing recovery after ejection of air following endoscopic exploratory tympanotomy. We propose that initial management for traumatic pneumolabyrinth should be ejection of the air bubble if it is located solely in the vestibule and sparing the cochlea.
Latest developments in living kidney donation
Authors: Hilbrands Luuk B. 
Published: December 2019

Purpose of review
Although the first successful kidney transplantation 65 years ago was performed with a living donor kidney, the number of living donor kidney transplantations has increased especially during the last 2 decades. The enlargement of living donor programs was made possible by new modes of living donation and by expansion of the living donor pool. At the same time, the long-term risks of kidney donation have been better delineated. In this review, the latest developments on these topics are summarized.

Recent findings
While the results of ABO-incompatible living kidney transplantation are superior to those of deceased donor transplantation, recent meta-analyses show a reduced patient and graft survival as compared with ABO compatible transplantation as well as increased risk of severe infection and bleeding. Kidney paired donation programs can be extended by including compatible couples and by advanced donation, although the latter raises ethical concerns. Living donors appear to have a higher risk of end-stage renal disease and this is especially true for obese donors and probably also for black donors with an APOL1 high-risk genotype. The importance of psychosocial outcomes after living kidney donation is increasingly recognized.

Summary
Living donor kidney transplantation remains the optimal treatment option for patients with end-stage renal disease. To increase the donor pool, a well developed paired kidney donation program and sufficient reimbursement of costs associated with donation are essential ingredients. Other ways of expanding the donor pool, such as ABO-incompatible transplantation, use of higher risk donors, providing donors with financial incentives and advanced donation are associated with medical, ethical and logistical complications. There should be a careful selection and follow-up of living kidney donors with attention for medical consequences as well as for psychosocial outcomes.
Evaluation of a Multimodal Resuscitation Program and Comparison of Mouth-to-Mouth and Bag-Mask Ventilation by Relatives of Children With Chronic Diseases*
Authors: Michel Jörg , Hofbeck Michael , Neunhoeffer Felix , Müller Manuel , Heimberg Ellen 
Published: December 2019

Objectives:
Children with chronic critical illness are at higher risk for cardiopulmonary arrests. Before chronically ill children are discharged from hospital, family members receive training in basic life support at many institutions. We evaluated whether a multimodal training program is able to teach adherence to current resuscitation guidelines and whether laypersons can be trained to perform both bag-mask ventilation and mouth-to-mouth ventilation equally effective in infants.

Design:
Prospective observational study.

Setting:
Pediatric critical care unit of a tertiary referral center.

Subjects:
Relatives of children with chronic illness prior to discharge from hospital.

Interventions:
Multimodal emergency and cardiopulmonary resuscitation training program.

Measurements and Main Results:
Following participation in our cardiopulmonary resuscitation training program 56 participants performed 112 simulated cardiopulmonary resuscitations (56 with mouth-to-mouth ventilation, 56 with bag-mask ventilation). Nearly all participants checked for consciousness and breathing. Shouting for help and activation of the emergency response system was only performed in half of the cases. There was almost full adherence to the resuscitation guidelines regarding number of chest compressions, chest compression rate, compression depth, full chest recoil, and duration of interruption of chest compression for rescue breaths. The comparison of mouth-to-mouth ventilation and bag-mask ventilation revealed no significant differences regarding the rate of successful ventilation (mouth-to-mouth ventilation: 77.1% ± 39.6%, bag-mask ventilation: 80.4% ± 38.0%; p = 0.39) and the cardiopulmonary resuscitation performance.

Conclusions:
A standardized multimodal cardiopulmonary resuscitation training program for family members of chronically ill children is effective to teach good cardiopulmonary resuscitation performance and adherence to resuscitation guidelines. Laypersons could be successfully trained to equally perform mouth-to-mouth and bag-mask ventilation technique.
Microglia Clear Neuron-released α-Synuclein via Selective Autophagy and Prevent Neurodegeneration
Authors: Choi Insup , Zhang Yuanxi , Seegobin Steven P. , Pruvost Mathilde , Wang Qian , Purtell Kerry , Zhang Bin , Yue Zhenyu 
Published: December 2019

AbstractMicroglia maintain brain homeostasis by removing neuron-derived components such as myelin and cell debris. The evidence linking microglia to neurodegenerative diseases is growing, however, the precise mechanisms remain poorly understood. Herein we report a neuroprotective role for microglia in the clearance of neuron-released α-synuclein. Neuronal α-synuclein activates microglia, which in turn engulf α-synuclein into autophagosomes for degradation via selective autophagy (termed Synucleinphagy). Synucleinphagy is initiated by the interaction of α-synuclein with Toll-like receptor 4 (TLR4), which induces transcriptional upregulation ofp62/SQSTM1through the NF-κB signaling pathway without causing TLR4 endocytosis. Induction of p62, an autophagy receptor, is necessary for the formation of α-synuclein/ubiquitin-positive puncta that are degraded by autophagy. Finally, disruption of microglial autophagy in mice expressing human α-synuclein promotes the accumulation of misfolded α-synuclein and causes midbrain dopaminergic neuron degeneration. Our study thus identifies a novel neuroprotective function of microglia in the clearance of α-synuclein via TLR4-NF-κB-p62 mediated Synucleinphagy.
REPIC: A database for exploringN6-methyladenosine methylome
Authors: Liu Shun , He Chuan , Chen Mengjie 
Published: December 2019

AbstractThe REPIC (RNAEpitranscriptomeCollection) database records about 10 million peaks called from publicly available m6A-seq and MeRIP-seq data using our unified pipeline. These data were collected from 672 samples of 49 studies, covering 61 cell lines or tissues in 11 organisms. REPIC allows users to queryN6-methyladenosine (m6A) modification sites by specific cell lines or tissue types. In addition, it integrates m6A/MeRIP-seq data with 1,418 histone ChIP-seq and 118 DNase-seq data tracks from the ENCODE project in a modern genome browser to present a comprehensive atlas of m6A, histone modification sites and chromatin accessibility regions. REPIC is accessible athttp://epicmod.uchicago.edu/repic.
Robust nucleation control via crisscross polymerization of DNA slats
Authors: Minev Dionis , Wintersinger Christopher M. , Ershova Anastasia , Shih William M. 
Published: December 2019

AbstractNatural biomolecular assemblies such as actin filaments or microtubules polymerize in a nucleation-limited fashion1,2. The barrier to nucleation arises in part from chelate cooperativity, where stable capture of incoming monomers requires straddling multiple subunits on a filament end3. For programmable self-assembly from building blocks such as synthetic DNA4–23, it is likewise desirable to be able to suppress spontaneous nucleation24–31. However, existing approaches that exploit just a low level of cooperativity can limit spontaneous nucleation only for slow growth, near-equilibrium conditions32. Here we introduce ultracooperative assembly of ribbons densely woven from single-stranded DNA slats. An inbound “crisscross” slat snakes over and under six or more previously captured slats on a growing ribbon end, forming weak but specific half-duplex interactions with each. We demonstrate growth of crisscross ribbons with distinct widths and twists to lengths representing many thousands of slat additions. Strictly seed-initiated extension is attainable over a broad range of temperatures, divalent-cation concentrations, and free-slat concentrations, without unseeded ribbons arising even after a hundred hours to the limit of agarose-gel detection. We envision that crisscross assembly will be broadly enabling for all-or-nothing formation of microstructures with nanoscale features, algorithmic self-assembly, and signal amplification in diagnostic applications requiring extreme sensitivity.
Bioremediation of chlorpyrifos and 3,5,6-trichloro-2-pyridinol (TCP) by a paddy field bacterial isolate: Insights from genome analysis for possible biodegradation pathway
Authors: Nayak Tanmaya , Adhya Tapan Kumar , Panda Ananta N , Das Bhaskar , Raina Vishakha 
Published: December 2019

AbstractChlorpyrifos (CP) is one of the world’s most widely used organophosphorous pesticides (OPs) in agriculture, has led to contaminate soil and water ecosystems along with human species. Here, we report a newly isolated strain,Ochrobactrumsp. CPD-03 form a paddy field which could degrade CP and its metabolite TCP (3,5,6-trichloro-2-pyridinol) in 48 hours with an efficiency of 85-88% in minimal salt medium. GC-MS analysis revealed possible metabolites during CP degradation. Whole genome analysis indicated the presence of arylesterase and existence of other genes accountable for xenobiotic compounds degradation. CPD-03 exhibited chemotactic features towards CP along with other OPs suggesting its versatile role for possible mineralization of these toxicants. Further screening of CPD-03 also displayed plant growth promoting activities. Taken altogether, our results highlight the potentials of this new isolateOchrobactrumsp. CPD-03 in bioremediation and application in OP-contaminated ecosystem.
Differences in Activation of Intracellular Signalling in Primary Human Retinal Endothelial Cells Between Isoforms of VEGFA-165
Authors: Dailey Wendelin , Shunemann Roberto , Yang Fang , Moore Megan , Knapp Austen , Chen Peter , Deshpande Mrinalini , Metcalf Brandon , Tompkins Quentin , Guzman Alvaro E. , Felisky Jennifer , Mitton Kenneth P. 
Published: December 2019

ABSTRACTPurposeThere are reports that a b-isoform of Vascular Endothelial Growth Factor-A-165 (VEGFA165b) is predominant in normal human vitreous, switching to the a-isoform (VEGFA165a) in the vitreous of some diseased eyes. While these isoforms appear to have a different ability to activate the VEGF-Receptor-2 (VEGFR2) in various endothelial cells, the nature of their ability to activate intracellular signalling pathways is not fully characterized, especially in retinal endothelial cells. We determined their activation potential for two key intracellular signalling pathways (MAPK, AKT) over complete dose-response curves and compared potential effects on the expression of several VEGFA165target genes in primary human retinal microvascular endothelial cells (HRMECs).MethodsTo determine full dose-response curves for the activation of MAPK (ERK1/2), AKT and VEGFR2, direct in-cell western assays were developed using primary Human Retinal Microvascular Endothelial Cells (HRMECs). Potential differences in dose-response effects on gene expression markers related to endothelial cell / leukocyte adhesion (ICAM1, VCAM1andSELE) and tight-junctions (CLDN5andOCLN) were tested by quantitative-PCR.ResultsActivation dose-response analysis revealed much stronger activation of MAPK, AKT and VEGFR2 by the a-isoform at lower doses. MAPK activation in primary HRMECs displayed a sigmoidal dose-response to a range of VEGFA165a concentrations spanning 10-250 pM, which shifted higher into the 100-5,000 pM range with VEGFA165b. Similar maximum activation of MAPK was achieved by both isoforms at high concentration. Maximum activation of AKT by VEGFA165b was only half of the maximum activation from VEGFA165a. At a lower intermediate dose, where VEGFA165a activated intracellular signalling stronger than VEGFA165b, the changes to VEGFA target gene expression was generally greater with VEGFA165a.ConclusionsIn primary HRMECs, VEGFA165a could maximally activate MAPK and AKT at lower concentrations where VEGFA165b had relatively little effect. The timing for maximal activation of MAPK was similar for both isoforms, which is different than reprorted for non-retinal endothelial cells. While VEGFA165a and VEGFA165b are limited to the sequence of their six C-terminal six amino acids, this results in a large difference in their ablility to activate at least two key intracellular signalling pathways and potentially VEGF target gene expression in primary human retinal endothelial cells.
Tubular STAT3 limits renal inflammation in autosomal dominant polycystic kidney disease
Authors: Viau Amandine , Baziz Maroua , Aka Amandine , Nguyen Clément , Kuehn E. Wolfgang , Terzi Fabiola , Bienaimé Frank 
Published: December 2019

ABSTRACTThe inactivation of the ciliary proteins polycystin 1 or 2 leads to autosomal dominant polycystic kidney disease (ADPKD), the leading genetic cause of chronic kidney disease. Both cilia signaling and interstitial inflammation play a critical role in the disease. Yet, the reciprocal interactions between immune and tubular cells are not well characterized. The transcription factor STAT3, which is suspected to fuel ADPKD progression, is involved in crosstalks between immune and non-immune cells in various tissues and is a component of the cilia proteome. Here, we explore how STAT3 intersects with cilia signaling, renal inflammation and cyst growth using conditional murine models of post-developmentalPkd1,Stat3and cilia ablation. Our results indicate that, although primary cilia directly modulate STAT3 activationin vitro, the bulk of STAT3 activation in polycystic kidneys occurs through an indirect mechanism in which primary cilia trigger macrophage recruitment to the kidney, which in turn promotes STAT3 activation. Surprisingly, while disruptingStat3inPkd1deficient tubules slightly reduced cyst burden, it resulted in a massive infiltration of the cystic kidneys by macrophages and T cells, precluding any improvement of kidney function. Mechanistically, STAT3 represses the expression of the inflammatory chemokines CCL5 and CXCL10 in polycystic kidneys and cultured tubular cells. These results demonstrate that STAT3 is not a critical driver of cyst growth in ADPKD but plays a major role in the crosstalk between immune and tubular cells that shapes disease expression.
Local adaptation fuels cryptic speciation in terrestrial annelids
Authors: Marchán Daniel Fernández , Novo Marta , Sánchez Nuria , Domínguez Jorge , Díaz Cosín Darío J. , Fernández Rosa 
Published: December 2019

AbstractUncovering the genetic and evolutionary basis of cryptic speciation is a major focus of evolutionary biology. Next Generation Sequencing (NGS) allows the identification of genome-wide local adaptation signatures, but has rarely been applied to cryptic complexes - particularly in the soil milieu - as is the case with integrative taxonomy. The earthworm genus Carpetania, comprising six previously suggested putative cryptic lineages, is a promising model to study the evolutionary phenomena shaping cryptic speciation in soil-dwelling lineages. Genotyping-By-Sequencing (GBS) was used to provide genome-wide information about genetic variability between seventeen populations, and geometric morphometrics analyses of genital chaetae were performed to investigate unexplored cryptic morphological evolution. Genomic analyses revealed the existence of three cryptic species, with half of the previously-identified potential cryptic lineages clustering within them. Local adaptation was detected in more than 800 genes putatively involved in a plethora of biological functions (most notably reproduction, metabolism, immunological response and morphogenesis). Several genes with selection signatures showed shared mutations for each of the cryptic species, and genes under selection were enriched in functions related to regulation of transcription, including SNPs located in UTR regions. Finally, geometric morphometrics approaches partially confirmed the phylogenetic signal of relevant morphological characters such as genital chaetae. Our study therefore unveils that local adaptation and regulatory divergence are key evolutionary forces orchestrating genome evolution in soil fauna.
Linker histone variant H1t is closely associated with repressed repeat-element chromatin domains in pachytene spermatocytes
Authors: Mahadevan Iyer Aditya , Kumar Sanjeev , Satyanarayana Rao Manchanahalli R. 
Published: December 2019

AbstractBackgroundH1t is the major linker histone variant in pachytene spermatocytes, where it constitutes 50-60% of total H1. This linker histone variant was previously reported to localize in the nucleolar rDNA element in mouse spermatocytes. Our main aim was to determine the extra-nucleolar localization of this linker histone variant in pachytene spermatocytes.ResultsWe generated H1t-specific antibodies in rabbits and validated its specificity by multiple assays like ELISA, western blot, etc. Genome-wide occupancy studies, as determined by ChIP-sequencing in P20 mouse testicular cells revealed that H1t did not closely associate with active gene promoters and open chromatin regions. Annotation of H1t bound genomic regions revealed that H1t is depleted from DSB hotspots and TSS, but are predominantly associated with retrotransposable repeat elements like LINE and LTR in pachytene spermatocytes. These chromatin domains are repressed based on co-association of H1t observed with methylated CpGs and repressive histone marks like H3K9me3 and H4K20me3 in vivo. Mass spectrometric analysis of proteins associated with H1t-containing oligonucleosomes identified piRNA-PIWI pathway proteins, repeat-repression associated proteins and heterochromatin proteins confirming the association with repressed repeat-element genomic regions. We validated the interaction of key proteins with H1t-containing oligonucleosomes by use of ChIP-western blot assays. On the other hand, we observe majority of H1t peaks to be associated with the intergenic spacer of the rDNA element, also in association with SINE elements of the rDNA element. Thus, we have identified the genomic and chromatin features of both nucleolar and extranucleolar localization patterns of linker histone H1t in the context of pachytene spermatocytes.ConclusionsH1t-containing repeat-element LINE and LTR chromatin domains are associated with repressive marks like methylated CpGs, histone modifications H3K9me3 and H4K20me3, and heterochromatin proteins like HP1β, Trim28, PIWIL1 etc. Apart from localisation of H1t at the rDNA element, we demonstrate the extranucleolar association of this linker histone variant at repeat-associated chromatin domains in pachytene spermatocytes. We hypothesize that H1t might induce local chromatin relaxation to recruit heterochromatin and repeat repression-associated protein factors necessary for TE (transposable element) repression, the final biological effect being formation of closed chromatin repressed structures.
Mesoscale Dynamics of Spectrin and Acto-Myosin shape Membrane Territories during Mechanoresponse
Authors: Ghisleni Andrea , Galli Camilla , Monzo Pascale , Ascione Flora , Fardin Marc-Antoine , Scita Giorgio , Li Qingsen , Maiuri Paolo , Gauthier Nils 
Published: December 2019

AbstractThe spectrin cytoskeleton is a major component of the cell cortex. While ubiquitously expressed, its dynamic interaction with the other cortex components, including the plasma membrane or the acto-myosin cytoskeleton, is poorly understood. Here, we investigated how the spectrin cytoskeleton re-organizes spatially and dynamically under the membrane during changes in cell mechanics. We found spectrin and acto-myosin cytoskeletons to be spatially distinct but cooperating during mechanical challenges, such as cell adhesion and contraction, or compression, stretch and osmolarity fluctuations, creating a cohesive cortex supporting the plasma membrane. Actin territories control protrusions and contractile structures while spectrin territories concentrate in retractile zones and low-actin density/inter-contractile regions, acting as a fence to organize membrane trafficking events. We unveil here the existence of a dynamic interplay between acto-myosin and spectrin cytoskeletons necessary to support a mesoscale organization of the lipid bilayer into spatially-confined cortical territories during cell mechanoresponse.