bluuebunny/crossref_metadata_2025 huggingface dataset:
Effective Reduction of Orbital Floor Fracture With Customized Balloon Using Contrast Agent And Micro Saw
Authors: Lee Sang Min , Leem Dae Ho
Published: November 2020

The purpose of this article is to introduce simple, minimally invasive, more effective, and more comfortable method using a customized balloon with contrast agent for orbital floor fracture. The customized balloon was fabricated to compensate for its shortcomings, based on the experiences from four patients who underwent the surgery of orbital floor fracture using a Foley catheter.

In a 33-year-old female patient with only orbital floor fracture, the reduction was performed using a transmaxillary approach with a customized balloon. The customized balloon was made using latex glove and 6 French gavage tube, and the contrast agent was injected within the balloon. A micro saw was used to form a window on the anterior wall of the maxillary sinus. Compared to the round bur, a micro saw can create an internal bevel along with minimal bone removal, which makes it possible to insert the bone fragment tightly without falling into the maxillary sinus when the fragment is repositioned. The use of contrast agent makes it more visible to determine the position of the balloon instantly during surgery by take portable radiograph. The balloon has removed after 3 weeks and no diplopia or no enophthalmos was observed. There remained very small defect on the anterior sinus wall about the size of gavage tube.

The transmaxillary approach, along with a conjunctival or subciliary approach, can be a good choice for the treatment of orbital fractures. Compared to the conventional Foley catheter, the application of a customized balloon and contrast agent supports the entire orbital floor evenly and wide, and fills the maxillary sinus without an empty space. It is easy to check the location of the balloon through x-ray photography during surgery, and has a very little discomfort for the patient.
Intraconal Orbital Hidrocystoma in an Infant
Authors: Bagheri Abbas , Veisi Amirreza , Rikhtehgar Mohamad Hasan , Kanavi Mozhgan Rezaei
Published: November 2020

Intraconal orbital hidrocystoma is a very rare entity. Herein, a 6-month old boy with an intraconal apocrine hidrocystoma will be reported. The patient presented with a left-sided mild proptosis and significant anisometropic hypermetropia. Clinical examinations revealed choroidal folds and optic disc blurring in the left eye. Orbital MRI disclosed an intraconal well-defined cystic lesion that was hypointense in T1 and hyperintense in T2 weighted images. The lesion was excised completely through a lateral orbitotomy and diagnosed histologically as an apocrine hidrocystoma. Excepting partial improvement of anisometropia, other clinical signs were improved after surgery.
Time-Lapse Between Presentation and Treatment of Mandibular Fractures: Is There a Correlation With Sensory Loss Recovery or No Recovery?
Authors: Yadav Sunil , Sachdeva Akash , Shekhawat Himanshu , Vinay
Published: November 2020

A prospective cohort study composed of 43 patients treated for unilateral mandibular fracture. The primary study variables were the post-traumatic IAN neurosensory score and the score after fracture reduction in two different groups on the basis of time lapse between presentation and treatment and displacement of mandible fracture. Appropriate descriptive and bivariate statistics were computed. The sample was analyzed over a one year period. It was observed that the recovery percentage (80%) was good in Group-A (n = 20) patients as compared to Group-B (n = 23) patients (43.47%) with significant P value of 0.015. Patients with displacement of ≥9 mm have neurosensory deficit of 80% while fracture displacement ≥ 5 mm to 8 mm have the neurosensory deficit of 34.21% which is significant with P value of 0.049. With each millimeter increase of displacement of fracture segments, more neurosensory deficit will be manifested. Delay in seeking in the treatment increases the risk because of continued movement. Where the injury is more severe, excessive displacement with increased time lapse from injury to surgical intervention, there is a higher possibility neurosensory deficit or no recovery. Early management can reduce the risk of permanent neurosensory deficits.
Associations Between Physical Activity and Changes in Depressive Symptoms and Health-related Quality of Life Across 7 Years After Roux-en-Y Gastric Bypass Surgery
Authors: King Wendy C. , Hinerman Amanda S. , White Gretchen E. , Courcoulas Anita P. , Belle Steven H.
Published: November 2020

Objective:

To examine associations of objectively-measured free-living physical activity (PA) with changes in depressive symptoms and mental and physical health-related quality of life (HRQoL) over 7 years after Roux-en-Y gastric bypass surgery (RYGB).

Background:

The contributions of PA to improvements in mental and physical health after RYGB, independent of weight loss, are unclear.

Methods:

Adults undergoing RYGB in a US multi-center cohort study wore an activity monitor and completed the Beck depression inventory (BDI) and 36-Item Short Form Health Survey (SF-36) annually ≤7 years (N = 646; 78% female, median age 47 years, median body mass index 46kg/m2). Linear mixed models estimated associations of quartiles of steps, sedentary behavior (SB), and moderate-to-vigorous intensity physical activity (MVPA), respectively, with pre-to-post-surgery changes in the BDI and SF-36 mental component summary and physical component summary scores, respectively, over 1–7 years post-surgery, with adjustment for sex, age, race, pre-surgery

body mass index, the respective pre-surgery score, treatment for depression (time-varying) and pre-to-post-surgery weight change (time-varying).

Results:

There were dose-response associations between steps, SB (inverse) and MVPA quartiles, respectively, with improvements in each score. Across follow-up, mean improvements in the BDI, Mental Component Summary and physical component summary scores, were 1.9 [95% confidence interval (CI), 1.0–2.8], 3.1 (95% CI, 1.5–4.7), and 4.0 (95% CI, 2.7–5.4) points higher, respectively, in the highest versus lowest steps quartile.

Conclusion:

Among adults who underwent RYGB, multiple objective PA measures were associated with decreases in depressive symptoms and improvements in mental and physical HRQoL throughout 7 years, independent of weight loss, indicating PA is a modifiable behavior to augment outcomes.
Percutaneous Internal Ring Suturing for the Minimal Invasive Treatment of Pediatric Inguinal Hernia: A 5-Year Single Surgeon Experience
Authors: Pogorelić Zenon , Čohadžić Tin , Jukić Miro , Nevešćanin Biliškov Ana
Published: November 2020

Purpose:

Percutaneous internal ring suturing (PIRS) is a minimally invasive surgical technique of laparoscopic hernia repair in children under the control of a laparoscope placed in the umbilicus. The aim of this study was to evaluate the management and postoperative outcomes of PIRS for inguinal hernia repair in children.

Patients and Methods:

All children who underwent PIRS for an inguinal hernia, between February 2015 and February 2020, were included in the prospective cohort study. The following parameters were recorded: age, gender, body mass index, lateralization of hernia, surgical and anesthesia times, level of pneumoperitoneum, additional trocar introduction, length of hospital stay, and intraoperative or postoperative complications and recurrences were recorded.

Results:

A total number of 228 PIRS procedures were performed in 188 children [126 (67%) male individuals and 62 (33%) female individuals] with a median age of 4 [interquartile range (IQR), 2 to 6] years and a median follow-up of 46 (IQR, 38 to 52) months. From the total number of hernia repairs there were 99 (52.7%) right, 49 (26.1%) left, and 40 (21.2%) bilateral hernia repairs. Median surgical time was 10 (IQR, 8 to 12) minutes for unilateral and 16 (IQR, 14 to 20) minutes for a bilateral repair. The median hospital stay was 24 (IQR, 8 to 24) hours. Regarding intraoperative complications, only 3 (1.3%) inferior epigastric veins injuries were recorded, without any consequences. During the follow-up period in 3 male children, hydrocele was recorded; in 2 cases, hydrocele resolved spontaneously and 1 required surgical treatment. No cases of other complications including testicular atrophy or recurrence were recorded.

Conclusion:

In a hands of an experienced pediatric laparoscopic surgeon, PIRS is a simple, safe, and effective technique for inguinal hernia repair in children with excellent outcomes, cosmetic results, and a low incidence of complications and recurrence.
Learning Curve in Robotic Primary Ventral Hernia Repair Using Intraperitoneal Onlay Mesh: A Cumulative Sum Analysis
Authors: Kudsi Omar Y. , Gokcal Fahri , Bou-Ayash Naseem , Crawford Allison S. , Chung Sebastian K. , Chang Karen , Litwin Demetrius
Published: November 2020

Background:

Cumulative sum (CUSUM) learning curves (LCs) are useful to analyze individual performance and to evaluate the acquisition of new skills and the evolution of those skills as experience is accumulated. The purpose of this study is to present a CUSUM LC based on the operative times of robotic intraperitoneal onlay mesh (rIPOM) ventral hernia repair (VHR) and identify differences observed throughout its phases.

Materials and Methods:

Patients who underwent rIPOM repair for elective, midline, and primary hernias were included. All procedures were performed exclusively by one surgeon within a 5-year period. CUSUM and risk-adjusted CUSUM were used to visualize the LC of rIPOM-VHR, based on operative times and complications. Once groups were obtained, univariate comparisons were performed.

Results:

Of the 90 rIPOM repairs, 25, 40, and 25 patients were allocated using a CUSUM analysis to the early, middle, and late phases, respectively. In terms of skin-to-skin times, the middle phase has a mean duration of 23 minutes shorter than the early phase (P<0.001), and the late phase has a mean duration 34 minutes shorter than the early phase (P<0.001). A steep decrease in off-console time was observed, with a 10-minute difference from early to middle phases. A consistent and gradual decrease in operative times was observed after completion of 36 cases, and a risk-adjusted CUSUM revealed improving outcomes after 55 cases.

Conclusions:

This study demonstrates and elucidates interval improvement in operative efficiency in rIPOM-VHR. Consistently decreasing operative times and simultaneous accumulated complication rates were observed after the completion of 55 cases.
Administration of valproic acid in clinically approved dose improves neurologic recovery and decreases brain lesion size in swine subjected to hemorrhagic shock and traumatic brain injury
Authors: Wakam Glenn K. , Biesterveld Ben E. , Pai Manjunath P. , Kemp Michael T. , O’Connell Rachel L. , Williams Aaron M. , Srinivasan Ashok , Chtraklin Kiril , Siddiqui Ali Z. , Bhatti Umar F. , Vercruysse Claire A. , Alam Hasan B.
Published: November 2020

BACKGROUND

Traumatic brain injury (TBI) and hemorrhage remain the leading causes of death after trauma. We have previously shown that a dose of valproic acid (VPA) at (150 mg/kg) can decrease brain lesion size and hasten neurologic recovery. The current Food and Drug Administration–approved dose of VPA is 60 mg/kg. We evaluate neurologic outcomes and brain lesion size of a single dose of VPA at a level currently within Food and Drug Administration–approved dose in swine subjected to TBI and hemorrhagic shock.

METHODS

Swine (n = 5/group) were subjected to TBI and 40% blood volume hemorrhage. Animals remained in shock for 2 hours before randomization to normal saline (NS) resuscitation alone (control), NS-VPA 150 mg/kg (VPA 150), or NS-VPA 50 mg/kg (VPA 50). Neurologic severity scores (range, 0–32) were assessed daily for 14 days, and brain lesion size was measured via magnetic resonance imaging on postinjury day (PID) 3.

RESULTS

Shock severity and laboratory values were similar in all groups. Valproic acid–treated animals demonstrated significantly less neurologic impairment on PID 1 and returned to baseline faster (PID 1 mean neurologic severity score, control = 22 ± 3 vs. VPA 150 mg/kg = 8 ± 7 or VPA 50 mg/kg = 6 ± 6; p = 0.02 and 0.003). Valproic acid–treated animals had significantly smaller brain lesion sizes (mean volume in mm3, control = 1,268.0 ± 241.2 vs. VPA 150 mg/kg = 620.4 ± 328.0 or VPA 50 mg/kg = 438.6 ± 234.8; p = 0.007 and 0.001).

CONCLUSION

In swine subjected to TBI and hemorrhagic shock, VPA treatment, in a dose that is approved for clinical use, decreases brain lesion size and reduces neurologic impairment compared with resuscitation alone.
Methods of visual assessment in children with cortical visual impairment
Authors: Chang Melinda Y. , Borchert Mark S.
Published: November 2020

Purpose of review

Cortical visual impairment (CVI) is the leading cause of pediatric visual impairment in developed countries. Currently, there is no standardized method of visual assessment in these children, who usually cannot participate in tests designed for typically developing children. A reproducible method of visual assessment that accurately reflects the multitude of visual deficits in CVI is critical to evaluate proposed therapies for this disorder. This review analyzes current research on methods of visual assessment in children with CVI.

Recent findings

Earlier studies focused on measuring visual acuity in children with CVI. More recent studies have emphasized other aspects of visual function, such as contrast sensitivity, motion detection, and visual search. Current research topics include questionnaires, functional vision assessment (CVI Range), neuropsychological tests of visual perception, and eye tracking. Eye tracking shows promise for visual assessment in both clinical and research settings because it is objective and quantitative, with the ability to assess diverse visual parameters.

Current research on visual assessment in children with CVI focuses on measuring deficits of visual function beyond visual acuity. This research represents an important step toward designing clinical trials to identify effective therapeutics for this increasingly prevalent disorder with heterogeneous manifestations.
The role of telemedicine in acute stroke treatment in times of pandemic
Authors: Hubert Gordian J. , Corea Francesco , Schlachetzki Felix
Published: November 2020

Purpose of review

The coronavirus disease 2019 (COVID-19) pandemic challenges many healthcare systems. This review provides an overview of the advantages of telemedicine during times of pandemic and the changes that have followed the outbreak of the COVID-19 disease.

Recent findings

Telemedicine has been utilized during infectious outbreaks for many years. COVID-19 has induced a variety of changes in laws (i.e. data privacy protection) and reimbursement procedures to accelerate new setups of telemedicine. Existing networks provide novel data about teleactivation resulting from social restrictions during the nadir of the lockdown in spring 2020.

Telemedicine is a safe and ideal expert support system for hospitals during infectious outbreaks. It makes high-quality medical procedures possible, limits potentially contagious interhospital transfers, saves critical resources such as protective gear and rescue/emergency transport services, and offers safe home office work for medical specialists.
Challenges of treatment adherence with direct oral anticoagulants in pandemic
Authors: Dittrich Tolga , Polymeris Alexandros , De Marchis Gian Marco
Published: November 2020

Purpose of review

Direct oral anticoagulants (DOAC) are crucial for the prevention of thromboembolic events in patients with nonvalvular atrial fibrillation. Drug adherence by the patient but also adherence to guidelines by the physician are suboptimal. This review highlights aspects of DOAC treatment during the coronavirus disease 2019 (COVID-19) pandemic and selected challenging scenarios.

Recent findings

For patients with a newly diagnosed indication for oral anticoagulation, a new interim clinical guidance recommends starting DOAC instead of vitamin K antagonists if DOAC are not contraindicated. The goal is to reduce the potential exposure of patients to severe acute respiratory syndrome coronavirus during the routine coagulation monitoring visits. As COVID-19 can lead to kidney failure, we discuss the challenges of DOAC dosing in kidney failures. Finally, we discuss two common challenges – when to start a DOAC after an ischemic stroke linked to atrial fibrillation, and whether cerebral microbleeds, including their count, are per se a contraindication to DOAC.

There are still open challenges regarding DOAC treatment on the patient and physician side, both related and unrelated to the pandemic.
Current advances in giant cell arteritis
Authors: Kaushik Megha , Ponte Cristina , Mollan Susan P.
Published: November 2020

Purpose of review

The aim of this study was to present the latest advances in giant cell arteritis (GCA) care, and recent national and international rheumatology societies guidance which influences clinical practice.

Recent findings

Cranial ultrasound reduces diagnostic delay and improves clinical outcomes. Immediate high dose glucocorticoids remain the standard treatment for GCA. Controlled trial evidence using Tocilizumab, an interleukin-6 receptor antagonist, shows good clinical efficacy with steroid-sparing effects.

Improved patient outcomes require formalizing pathways to diagnosis and closer liaison with rheumatology for long-term management with second-line therapies.
The clinical significance of simultaneous detection of pathogens from bronchoalveolar lavage fluid and blood samples by metagenomic next-generation sequencing in patients with severe pneumonia
Authors: Chen Jinlian , Zhao Yuxi , Shang Yongpeng , Lin Zhiwei , Xu Guangjian , Bai Bing , Zheng Jinxin , Li Peiyu , Mao Yuanchen , Deng Qiwen , Yu Zhijian
Published: November 2020

Introduction. Bloodstream infection is a common complication in patients with severe pneumonia and is regarded as an independent risk factor for prediction of poor outcome. Metagenomic next-generation sequencing (mNGS) has been widely applied for pathogen determination of various clinical specimens from patients with infectious diseases. However, the clinical significance of and necessity for simultaneous pathogen detection of both blood samples and bronchoalveolar lavage fluid (BALF) by mNGS in patients with severe pneumonia remains unclear.

Hypothesis/Gap Statement. Simultaneous detection of pathogens from both BALF and blood samples in patients with severe pneumonia helps to determine the complication of the bloodstream infection.

Aims. This study aimed to elucidate the clinical significance and necessity of pathogen detection simultaneously in both blood samples and BALF samples with the application of mNGS in patients with severe pneumonia.

Methods. In this study, 20 patients with severe pneumonia were enrolled and the potential pathogens in both BALF and blood samples were detected simultaneously by conventional microbial examination and mNGS tests. Moreover, multiple consecutive microbial detections were undertaken to investigate the dynamic variation of pathogens during the course of disease progression in two of the 20 patients.

Results. In 85 % (17/20) of the patients with severe pneumonia, various pathogens were determined positively in the BALF by mNGS, including 10 cases with bacterial infection, five cases with viral infection and two cases with fungal infection. By contrast, pathogens in 50 % (10/20) of cases could be detected positively in the BALF by conventional microbial tests. Among 17 severe pneumonia patients with mNGS-positive BALF, pathogens were also identified in 10 cases with mNGS-positive blood samples. By contrast, only one patient complicated with a bloodstream infection could be found by conventional bacterial culture. Moreover, the pathogens from BALF were highly consistent with that from blood samples detected by mNGS in the early stage of the disease. With disease progression and after recurrent antibiotic treatment, significant dynamic changes of the microbial species from the BALF and blood samples could be clearly found by mNGS.

Conclusions. This study emphasizes the utility of mNGS in the rapid simultaneous detection of pathogens from both BALF and blood samples in patients with severe pneumonia, and could allow determination of bloodstream infection and guide clinicians regarding antimicrobial treatments.
A repurposed, blood gene signature is associated with poor outcomes in SARS-CoV-2
Authors: Juan-Guardela Brenda M. , Sun Jiehuan , Zhang Tong , Xu Bing , Michaud Gaetane , Herazo-Maya Jose D.
Published: November 2020

Poor outcomes after SARS-CoV-2 infection are difficult to predict. Survivors may develop pulmonary fibrosis. We previously identified a 52-gene signature in peripheral blood, predictive of mortality in Idiopathic Pulmonary Fibrosis. In this study, we analyzed this signature in SARS-CoV-2 infected individuals and identified genomic risk profiles with significant differences in outcomes. Analysis of single cell expression data shows that monocytes, red blood cells, neutrophils and dendritic cells are the cellular source of the high risk gene signature.
A Synthetic Defective Interfering SARS-CoV-2
Authors: Yao Shun , Narayanan Anoop , Majowicz Sydney , Jose Joyce , Archetti Marco
Published: November 2020

Viruses thrive by exploiting the cells they infect but must also produce viral proteins to replicate and infect other cells. As a consequence, they are also susceptible to exploitation by defective versions of themselves that do not produce such proteins. A defective viral genome with deletions in protein-coding genes could still replicate in cells coinfected with full-length viruses, and even replicate faster due to its shorter size, interfering with the replication of the virus. We have created a synthetic defective interfering version of SARS-CoV-2, the virus causing the recent Covid-19 pandemic, assembling parts of the viral genome that do not code for any functional protein but enable it to be replicated and packaged. This synthetic defective genome replicates three times faster than SARS-CoV-2 in coinfected cells, and interferes with it, reducing the viral load of a cell by half in 24 hours. The synthetic genome is transmitted as efficiently as the full-length genome, confirming the location of the putative packaging signal of SARS-CoV-2. A version of such a synthetic construct could be used as a self-promoting antiviral therapy: by enabling replication of the synthetic genome, the virus promotes its own demise.

Graphic summary
Lineages of embryonic stem cells show non-Markovian state transitions
Authors: Udomlumleart Tee , Hu Sofia , Garg Salil
Published: November 2020

Pluripotent embryonic stem cells (ESCs) contain the ability to constitute the cell types of the adult vertebrate through a series of developmental state transitions. In culture, ESCs reversibly transition between states in a manner previously described as stochastic. However, whether ESCs retain memory of their previous states or transition in a memoryless (Markovian) process remains relatively unknown. Here we show lineages of ESCs do not exhibit the Markovian property: their previous states and kin relations influence future choices. In a subset of lineages, related ESCs remain likely to occupy the same state weeks after labeling. Unexpectedly, the distribution of lineages across states away from the equilibrium point predicted by a Markov model remains consistent over time, suggesting a conservation of informational entropy in this system. Additionally, some lineages appear highly dynamic in their ability to switch states but do not dominate the culture, suggesting that state switching is a separable property from growth. Together, these data suggest ESC state transitions are a proscribed process governed by additional variables.
Nucleosome plasticity is a critical element of chromatin liquid–liquid phase separation and multivalent nucleosome interactions
Authors: Farr Stephen E. , Woods Esmae J. , Joseph Jerelle A. , Garaizar Adiran , Collepardo-Guevara Rosana
Published: November 2020

Liquid–liquid phase separation (LLPS) of chromatin is an important mechanism that helps explain the membrane-less compartmentalization of the nucleus. Because chromatin compaction and LLPS are collective phenomena, linking their modulation to biophysical features of individual nucleosomes is challenging. Here, we develop a novel multiscale chromatin model that integrates atomistic representations, a chemically-specific coarse-grained model, and a minimal model. In tandem, we devise a transferable Debye-length exchange molecular dynamics approach to achieve enhanced sampling of high-resolution chromatin. We find that nucleosome thermal fluctuations become significant at physiological salt concentrations and destabilize the 30-nm fiber. Nucleosome breathing favors stochastic folding of chromatin and promotes LLPS by simultaneously boosting the transient nature and heterogeneity of nucleosome–nucleosome contacts, and the effective nucleosome valency. Our results put forward the intrinsic plasticity of nucleosomes as a key element in the liquid-like behavior of chromatin, and help reconcile longstanding differences between fiber-based and in vivo chromatin models.
Household-Level Risk Factors forAedes aegyptiPupal Density in Guayaquil, Ecuador
Authors: Ha Thien-An , León Tomás M. , Lalangui Karina , Ponce Patricio , Marshall John M. , Cevallos Varsovia
Published: November 2020

Background

Vector-borne diseases are a major cause of disease burden in Guayaquil, Ecuador, especially arboviruses spread byAedes aegyptimosquitoes. Understanding which household characteristics and risk factors lead to higherAe. aegyptidensities and consequent disease risk can help inform and optimize vector control programs.

Methods

Cross-sectional entomological surveys were conducted in Guayaquil between 2013 and 2016, covering household demographics, municipal services, potential breeding containers, presence ofAe. aegyptilarvae and pupae, and history of using mosquito control methods. A zero-truncated negative binomial regression model was fitted to data for estimating the household pupal index. An additional model assessed the factors of the most productive breeding sites across all of the households.

Results

Of surveyed households, 610 satisfied inclusion criteria. The final household-level model found that collection of large solid items (e.g., furniture and tires) and rainfall the week of and 2 weeks before collection were negatively correlated with average pupae per container, while bed canopy use, unemployment, container water volume, and the interaction between large solid collection and rainfall 2 weeks before the sampling event were positively correlated. Selection of these variables across other top candidate models with ΔAICc < 1 was robust, with the strongest effects from large solid collection and bed canopy use. The final container-level model explaining the characteristics of breeding sites found that contaminated water is positively correlated withAe. aegyptipupae counts while breeding sites composed of car parts, furniture, sewerage parts, vases, ceramic material, glass material, metal material, and plastic material were all negatively correlated.

Conclusion

Having access to municipal services like bulky item pickup was effective at reducing mosquito proliferation in households. Association of bed canopy use with higher mosquito densities is unexpected, and may be a consequence of large local mosquito populations or due to limited use or effectiveness of other vector control methods. The impact of rainfall on mosquito density is multifaceted, as it may both create new habitat and “wash out” existing habitat. Providing services and social/technical interventions focused on monitoring and eliminating productive breeding sites is important for reducing aquatic-stage mosquito densities in households at risk forAe. aegypti-transmitteddiseases.
Transcriptional regulation ofZIPgenes is independent of local zinc status in Brachypodium shoots upon zinc deficiency and resupply
Authors: Amini Sahand , Arsova Borjana , Gobert Sylvie , Carnol Monique , Bosman Bernard , Motte Patrick , Watt Michelle , Hanikenne Marc
Published: November 2020

The biological processes underlying zinc homeostasis are targets for genetic improvement of crops to counter human malnutrition. Detailed phenotyping, ionomic, RNA-Seq analyses and flux measurements with67Zn isotope revealed whole plant molecular events underlying zinc homeostasis upon varying zinc supply and during zinc resupply to starvedBrachypodium distachyon(Brachypodium) plants. Although both zinc deficiency and excess hindered Brachypodium growth, accumulation of biomass and micronutrients into roots and shoots differed depending on zinc supply. The zinc resupply dynamics involved 1893 zinc-responsive genes. Multiple ZIP transporter genes and dozens of other genes were rapidly and transiently down-regulated in early stages of zinc resupply, suggesting a transient zinc shock, sensed locally in roots. Notably genes with identical regulation were observed in shoots without zinc accumulation, pointing to root-to-shoot signals mediating whole plant responses to zinc resupply. Molecular events uncovered in the grass model Brachypodium are useful for the improvement of staple monocots.
Protein interactions between the oral bacteriaFusobacterium nucleatumandPorphyromonas gingivalisin biofilm and planktonic culture
Authors: Mohammed Marwan Mansoor Ali , Pettersen Veronika Kuchařová , Nerland Audun H. , Wiker Harald G. , Bakken Vidar
Published: November 2020

The opportunistic pathogensFusobacterium nucleatumandPorphyromonas gingivalisare Gram-negative bacteria associated with oral biofilm and periodontal disease. Although liquid cultures are often the preferred cultivation method in microbiology, bacterial cells in biofilm adopt a profoundly different phenotype reflecting the close cell-to-cell contact compare to their planktonic counterparts. To investigateF. nucleatumandP. gingivalisinteractions relevant in biofilm formation, we applied liquid chromatography-tandem mass spectrometry to determine the expressed proteome ofF. nucleatumandP. gingivaliscells that were grown either as biofilm or in planktonic culture, and individually or together.

The proteomic analyses detected 1,322F. nucleatumand 966P. gingivalisproteins. We statistically compared the proteins label-free quantitative (LFQ) intensities between biofilm and planktonic culture and identified significant changes (p-value ≤0.05) in 0,4%F. nucleatumproteins, 7%P. gingivalisproteins, and more than 14% of all proteins in the dual-species model. For both species, proteins involved in vitamin B2 (riboflavin) metabolic process had significantly increased levels in the biofilm condition. In both mono- and dual-species biofilm models,P. gingivalisincreased the production of proteins functional in translation, oxidation-reduction, and amino acid metabolism, when compared to planktonic cultures. However, when we compared LFQ intensities between mono- and dual-species models, over 90% of the significantly changedP. gingivalisproteins had their levels reduced in biofilm and planktonic settings of the dual-species model.

Our findings suggest that the two bacteria interact with each other at the protein level and indicate thatP. gingivalisreduces the production of multiple proteins because of more favourable growth conditions provided byF. nucleatumpresence. The results highlight the complex interactions of bacteria contributing to oral biofilm, which need to be considered in the design of future prevention strategies.
Improving water quality does not guarantee fish health: effects of ammonia pollution on the behaviour of wild-caught pre-exposed fish
Authors: Soler Patricia , Faria Melissa , Barata Carlos , García-Galea Eduardo , Lorente Beatriz , Vinyoles Dolors
Published: November 2020

Ammonia is a pollutant frequently found in aquatic ecosystems. In fish, ammonia can cause physical damage, alter its behaviour and even cause death. Exposure to ammonia also increases fish physiological stress, which can be measured through biomarkers. In this study, we analysed the effect of sublethal ammonia concentrations on the behaviour and the oxidative stress ofBarbus meridionalisthat had been pre-exposed to this compound in the wild. Wild-caught fish from a polluted site (pre-exposed fish) and from an unpolluted site (non-pre-exposed fish) were exposed, under experimental conditions, to total ammonia concentrations (TAN) of 0, 1, 5 and 8 mg/L. Swimming activity, feeding behaviour and oxidative stress response based on biomarkers were analysed. Pre-exposed fish showed both an altered behaviour and an altered oxidative stress response in the control treatment (0 mg/L). Differences in swimming activity were also found as pre-exposed fish swam less. Lower feeding activity (voracity and satiety) and altered response to oxidative stress were also observed at ≥ 1 mg/L TAN. Biomarker results confirmed pre-exposed fish suffer from a reduction in their antioxidant defences and, hence, showed increased oxidative tissue damage. In summary, pre-exposed fish showed more sensitivity to ammonia exposure than fish from a pristine site.
MarcoPolo: a clustering-free approach to the exploration of differentially expressed genes along with group information in single-cell RNA-seq data
Authors: Kim Chanwoo , Lee Hanbin , Jeong Juhee , Jung Keehoon , Han Buhm
Published: November 2020

A common approach to analyzing single-cell RNA-sequencing data is to cluster cells first and then identify differentially expressed genes based on the clustering result. However, clustering has an innate uncertainty and can be imperfect, undermining the reliability of differential expression analysis results. To overcome this challenge, we present MarcoPolo, a clustering-free approach to exploring differentially expressed genes. To find informative genes without clustering, MarcoPolo exploits the bimodality of gene expression to learn the group information of the cells with respect to the expression level directly from given data. Using simulations and real data analyses, we showed that our method puts biologically informative genes at high ranks more robustly than other existing methods. As our method provides information on how cells can be grouped for each gene, it can help identify cell types that are not separated well in the standard clustering process. Our method can also be used as a feature selection method to improve the robustness of the dimension reduction against changes in the parameters involved in the process.
Axon-secreted chemokine-like Orion is a signal for astrocyte infiltration during neuronal remodeling
Authors: Boulanger Ana , Thinat Camille , Züchner Stephan , Fradkin Lee G. , Lortat-Jacob Hugues , Dura Jean-Maurice
Published: November 2020

The remodeling of neurons is a conserved fundamental mechanism underlying nervous system maturation and function. Glial cells are known to clear neuronal debris but also to have an active role in the remodeling process. Developmental axon pruning ofDrosophilamemory center neurons occurs by a degenerative process mediated by infiltrating astrocytes. However, how these glial processes are recruited by the axons is unknown. In an unbiased screen, we identified a new gene (orion) which is necessary for both the pruning of some axons and removal of the resulting debris. Orion is secreted from the neurons and bears some features common to the chemokines, a family of chemoattractant cytokines. Thus, chemokine involvement in neuron/glial cell interaction is an evolutionarily ancient mechanism. We propose that Orion is the neuronal signal that elicits astrocyte infiltration required for developmental neuronal remodeling.
DisA limits RecA- and RadA/Sms-mediated replication fork remodelling to prevent genome instability
Authors: Torres Rubén , Alonso Juan C.
Published: November 2020

The DisA diadenylate cyclase (DAC), the DNA helicase RadA/Sms and the RecA recombinase are required to prevent a DNA replication stress during the revival of haploidBacillus subtilisspores. Moreover,disA, radAandrecAare epistatic among them in response to DNA damage. We show that DisA inhibits the ATPase activity of RadA/Sms C13A by competing for single-stranded (ss) DNA. In addition, DisA inhibits the helicase activity of RadA/Sms. RecA filamented onto ssDNA interacts with and recruits DisA and RadA/Sms onto branched DNA intermediates. In fact, RecA binds a reversed fork and facilitates RadA/Sms-mediated unwinding to restore a 3′-fork intermediate, but DisA inhibits it. Finally, RadA/Sms inhibits DisA DAC activity, but RecA counters this negative effect. We propose that RecA, DisA and RadA/Sms interactions, which are mutually exclusive, limit remodelling of stalled replication forks. DisA, in concert with RecA and/or RadA/Sms, indirectly contributes to template switching or lesion bypass, prevents fork breakage and facilitates the recovery of c-di-AMP levels to re-initiate cell proliferation.

Subject Categories

Genomic stability & Dynamics
find-tfbs: a tool to identify functional non-coding variants associated with complex human traits using open chromatin maps and phased whole-genome sequences
Authors: de Bellefon Sébastian Méric , Thibord Florian , Auer Paul L. , Blangero John , Coban-Akdemir Zeynep H , Floyd James S. , Fornage Myriam , Johnsen Jill M. , Lange Leslie A. , Lewis Joshua P. , Mathias Rasika A. , McHugh Caitlin P. , Moon Jee-Young , Reiner Alex P. , Stilp Adrienne M. ,   NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, Lettre Guillaume
Published: November 2020

Motivation

Whole-genome DNA sequencing (WGS) enables the discovery of non-coding variants, but tools are lacking to prioritize the subset that functionally impacts human phenotypes. DNA sequence variants that disrupt or create transcription factor binding sites (TFBS) can modulate gene expression. find-tfbs efficiently scans phased WGS in large cohorts to identify and count TFBSs in regulatory sequences. This information can then be used in association testing to find putatively functional non-coding variants associated with complex human diseases or traits.

Results

We applied find-tfbs to discover functional non-coding variants associated with hematological traits in the NHLBI Trans-Omics for Precision Medicine (TOPMed) WGS dataset (Nmax=44,709). We identified >2000 associations atP<1×10−9, implicating specific blood cell-types, transcription factors and causal genes. The vast majority of these associations are captured by variants identified in large genome-wide association studies (GWAS) for blood-cell traits. find-tfbs is computationally efficient and robust, allowing for the rapid identification of non-coding variants associated with multiple human phenotypes in very large sample size.

Availability

https://github.com/Helkafen/find-tfbsandhttps://github.com/Helkafen/find-tfbs-demo

Contacts

sebastian.meric.de.bellefon@umontreal.caandguillaume.lettre@umontreal.ca

Supplementary information

Supplementary data are available.
The multidisciplinary nature of COVID-19 research
Authors: Arencibia-Jorge Ricardo , García-García Lourdes , Galbán-Rodríguez Ernesto , Carrillo-Calvet Humberto
Published: November 2020

Objective

We analyzed the scientific output after COVID-19 and contrasted it with studies published in the aftermath of seven epidemics/pandemics: Severe Acute Respiratory Syndrome (SARS), Influenza A virus H5N1 and Influenza A virus H1N1 human infections, Middle East Respiratory Syndrome (MERS), Ebola virus disease, Zika virus disease, and Dengue.

Design/Methodology/Approach

We examined bibliometric measures for COVID-19 and the rest of studied epidemics/pandemics. Data were extracted from Web of Science, using its journal classification scheme as a proxy to quantify the multidisciplinary coverage of scientific output. We proposed a novel Thematic Dispersion Index (TDI) for the analysis of pandemic early stages.

Results/Discussion

The literature on the seven epidemics/pandemics before COVID-19 has shown explosive growth of the scientific production and continuous impact during the first three years following each emergence or re-emergence of the specific infectious disease. A subsequent decline was observed with the progressive control of each health emergency. We observed an unprecedented growth in COVID-19 scientific production. TDI measured for COVID-19 (29,4) in just six months, was higher than TDI of the rest (7,5 to 21) during the first three years after epidemic initiation.

Conclusions

COVID-19 literature showed the broadest subject coverage, which is clearly a consecuence of its social, economic, and political impact. The proposed indicator (TDI), allowed the study of multidisciplinarity, differentiating the thematic complexity of COVID-19 from the previous seven epidemics/pandemics.

Originality/Value

The multidisciplinary nature and thematic complexity of COVID-19 research were successfully analyzed through a scientometric perspective.
Contextual inference underlies the learning of sensorimotor repertoires
Authors: Heald James B. , Lengyel Máté , Wolpert Daniel M.
Published: November 2020

Humans spend a lifetime learning, storing and refining a repertoire of motor memories. However, it is unknown what principle underlies the way our continuous stream of sensorimotor experience is segmented into separate memories and how we adapt and use this growing repertoire. Here we develop a principled theory of motor learning based on the key insight that memory creation, updating, and expression are all controlled by a single computation – contextual inference. Unlike dominant theories of single-context learning, our repertoire-learning model accounts for key features of motor learning that had no unified explanation and predicts novel phenomena, which we confirm experimentally. These results suggest that contextual inference is the key principle underlying how a diverse set of experiences is reflected in motor behavior.
Bio-Physical Modeling ofGalvanicHuman Body Communication in Electro-Quasistatic Regime
Authors: Modak Nirmoy , Nath Mayukh , Chatterjee Baibhab , Maity Shovan , Sen Shreyas
Published: November 2020

Human Body Communication (HBC) is an alternative to radio wave-based Wireless Body Area Network (WBAN) because of its low-loss, wide bandwidth leading to enhanced energy efficiency. HBC also shows better performance in terms of physical security as most of the signal is confined within the body. To obtain optimum performance and usability, modeling of the body channel plays a vital role. Out of two HBC modalities, Galvanic HBC has the promise to provide lower loss compare to Capacitive HBC for shorter channel length. In this paper, we present the first lumped element based detailed model of Galvanic HBC channel which is used to explain the dependency of channel loss on the material property of skin, fat and muscle tissue layer along with electrode size, electrode separation, geometrical position of the electrodes and return path capacitance. The model considers the impedance of skin and muscle tissue layers and the effect of various coupling capacitances between the body and Tx/Rx electrodes to the Earth-ground. A 2D planner structure is simulated in HFSS to prove the validity of the proposed model. The effect ofsymmetryandasymmetryat the transmitter and receiver end are also explained using the model. The experimental results show that, due to the mismatch at the transmitter and receiver side, the loss increases gradually with channel length and saturates to a finite value as channel length becomes significantly longer compare to the transmitting or receiving electrode pair separation.
Elevated cerebrospinal fluid cytokine levels in tuberculous meningitis predict survival in response to dexamethasone
Authors: Whitworth Laura , Troll Rajan , Pagán Antonio J. , Roca Francisco , Edelstein Paul H. , Troll Mark , Tobin David , Phu Nguyen Hoan , Bang Nguyen Duc , Thwaites Guy , Thuong Nguyen Thuy Thuong , Sewell Roger , Ramakrishnan Lalita
Published: November 2020

Adjunctive treatment with anti-inflammatory corticosteroids like dexamethasone increases survival in tuberculosis meningitis. Dexamethasone responsiveness associates with a C/T variant inLeukotriene A4 Hydrolase (LTA4H), which regulates expression of the pro-inflammatory mediator leukotriene B4 (LTB4). TT homozygotes, with increased LTB4, have the highest survival when treated with dexamethasone and the lowest survival without. While the T allele is present in only a minority of the world’s population, corticosteroids confer modest survival benefit worldwide. Using Bayesian methods, we examined how pre-treatment levels of cerebrospinal fluid (CSF) pro-inflammatory cytokines affect survival in dexamethasone-treated tuberculous meningitis.LTA4HTT homozygosity was associated with global cytokine increases, including TNF. Association between higher cytokine levels and survival extended to non-TT patients, suggesting that other genetic variants may also induce dexamethasone-responsive pathological inflammation. These findings warrant studies that tailor dexamethasone therapy to pre-treatment CSF cytokine concentrations, while searching for additional genetic loci shaping the inflammatory milieu.
Development of a multiplexed targeted mass spectrometry assay for LRRK2-phosphorylated Rabs and Ser910/Ser935 biomarker sites
Authors: Nirujogi Raja S. , Tonelli Francesca , Taylor Matthew , Lis Pawel , Zimprich Alexander , Sammler Esther , Alessi Dario R
Published: November 2020

Mutations that increase the protein kinase activity of LRRK2 are one of the most common causes of familial Parkinson’s disease. LRRK2 phosphorylates a subset of Rab GTPases within their Switch-II motif, impacting interaction with effectors. We describe and validate a new, multiplexed targeted mass spectrometry assay to quantify endogenous levels of LRRK2-phosphorylated Rab substrates (Rab1, Rab3, Rab8, Rab10, Rab35 and Rab43) as well as total levels of Rabs, LRRK2 and LRRK2-phosphorylated at the Ser910 and Ser935 biomarker sites. Exploiting this assay, we quantify for the first time the relative levels of each of the pRab proteins in different cells (mouse embryonic fibroblasts, human neutrophils) and mouse tissues (brain, kidney, lung and spleen). We define how these components are impacted by Parkinson’s pathogenic mutations (LRRK2[R1441C] and VPS35[D620N]) and LRRK2 inhibitors. We find that the VPS35[D620N], but not LRRK2[R1441C] mutation, enhances Rab1 phosphorylation in a manner blocked by administration of an LRRK2 inhibitor, providing the first evidence that endogenous Rab1 is a physiological substrate for LRRK2. We exploit this assay to demonstrate that in Parkinson’s patients with VPS35[D620N] mutations, phosphorylation of multiple Rab proteins (Rab1, Rab3, Rab8, Rab10 and Rab43) is elevated. We highlight the benefits of this assay over immunoblotting approaches currently deployed to assess LRRK2 Rab signalling pathway.