bluuebunny/crossref_metadata_2025 huggingface dataset:
Reconstruction of bilateral inferomedial gluteal defects after resection of hidradenitis suppurativa with symmetrical keystone flaps designed parallel to relaxed skin-tension lines
Authors: Kim Hyo Bong , Lim Soo Yeon , Yoon Chi Sun , Kim Kyu Nam
Published: April 2020

Rationale:

Surgical treatment of hidradenitis suppurativa (HS) is challenging. Wide excision of affected lesions followed by skin graft or flap coverage has been recommended to achieve remission and prevent recurrence. Herein, we present our experience of bilateral inferomedial gluteal defects coverage using symmetrical keystone flaps (KFs) designed parallel to relaxed skin-tension lines (RSTLs).

Patient concerns:

An 18-year-old man was admitted for chronic inflammatory lesions in both inferomedial gluteal areas.

Diagnoses:

Physical examination revealed multiple sinuses with broad surrounding scars in both inferomedial gluteal areas, which led to a diagnosis of HS.

Interventions:

We performed wide excision on all affected lesions. The size of the final defects was 6 × 10 cm on the right side, and 5 × 9 cm on the left side. We covered the defects with KFs 9 × 15 cm (right) and 8 × 12 cm (left), which were based on the hotspots of the interior gluteal artery and internal pudendal artery perforators, and parallel to RSTLs.

Outcomes:

The flaps were inset without tension on each side, and the donor sites were closed primarily. All flaps fully survived and there were no postoperative complications. The patient was satisfied with the final outcome after 6 months of follow-up.

Lessons:

Successful reconstruction of bilateral inferomedial gluteal defects was achieved after resection of HS using symmetrical KFs designed parallel to RSTLs. The KF technique considering RSTLs could be a good reconstructive option for gluteal HS.
Successful treatment with matched unrelated donor peripheral blood stem cell transplantation for very severe aplastic anemia in presence of active infections
Authors: Huang Yu-Rong , Xie Cai-Qin , Tong Jie-Feng , Zhang Xiao-Hong , Xu Yang , Yuan Xiang-Gui
Published: April 2020

Rationale:

Very severe aplastic anemia (vSAA) with active infections is always fatal. Adequate infection control before hematopoietic stem cell transplantation is recommended.

Patient concerns:

A 38-year-old woman with vSAA suffered from acute perforated appendicitis and invasive pulmonary fungal infection, and she failed to respond to intense antimicrobial therapies.

Diagnosis:

She was diagnosed with refractory vSAA with stubborn acute perforated appendicitis and invasive pulmonary fungal infection.

Interventions:

We successfully completed an emergent reduced intensity conditioning-matched unrelated donor (MUD)-peripheral blood stem cell transplantation (PBSCT) as a salvage therapy in the presence of active infections. The conditioning regimens consisted of reduced cyclophosphamide 30 mg/kg/day from day-5 to day-3, fludarabine 30 mg/m2/day from day-5 to day-3 and porcine-antilymphocyte immunoglobulin 15 mg/kg/day from day-4 to day-2 without total body irradiation. Cyclosporin A, mycophenolate mofetil and short-term methotrexate were administered as graft-versus-host disease (GVHD) prophylaxis. Neutrophils and platelets were engrafted on day+15 and day+21. Appendiceal abscess and severe pneumonia developed after neutrophil engraftment, which were successfully managed with intense antimicrobial therapy and surgical intervention.

Outcomes:

Only limited cutaneous chronic GVHD was observed 5 months after transplantation. The patient still lives in a good quality of life 2 years after transplantation.

Lessons:

Active infections may be no longer a contraindication to hematopoietic stem cell transplantation for some patients with vSAA.
Standardized approach of albumin, midodrine and octreotide on hepatorenal syndrome treatment response rate
Authors: Hiruy Aklil , Nelson Joelle , Zori Andreas , Morelli Giuseppe , Cabrera Roniel , Kamel Amir
Published: April 2020

Background:

Hepatorenal syndrome (HRS) remains a serious complication of cirrhosis with a high mortality rate. There is little information on the effect of standardizing albumin, midodrine and octreotide combination on treatment response in patients with HRS.

Objective:

The aim of the study was to determine the impact of a standardized HRS treatment regimen on renal function recovery. The primary outcome was full response rate. Secondary outcomes included partial and no response rates, 30-day all-cause mortality, ICU length of stay (LOS), hospital LOS, liver transplantation and total dose of albumin.

Methods:

This retrospective study evaluated the impact of using a standardized approach with albumin, midodrine and octreotide on treatment response rates compared to a historical group.

Results:

Of the patients with HRS, 28 received a standardized approach with albumin, midodrine and octreotide while 60 received a nonstandardized approach. Ten percent of patients achieved full response in the prestandardization group compared with 25% in the poststandardization group (P = 0.07). Renal replacement therapy was significantly more prevalent in the prestandardization group vs. poststandardization group (45% vs. 21.4%, P = 0.03). Liver transplantation was performed significantly more often in the prestandardization group compared the poststandardization group (23% vs. 3.6%, P = 0.02). Amount of albumin used was statistically lower in the poststandardization group (425 vs. 332 g, P = 0.05). No significant differences in days of HRS treatment, mortality rate, hospital and ICU LOS were observed.

Conclusion:

A trend towards improved treatment response rate was observed after standardizing the HRS treatment regimen. Standardized therapy led to significantly lower rates of renal replacement therapy and liver transplantation, suggesting patients in poststandardization were effectively managed medically without requiring further intervention.
Role of noninvasive tools for prediction of clinically evident portal hypertension in children
Authors: Kumar Aditi , Lal Sadhna B. , Bhatia Anmol , Das Ashim
Published: April 2020

Background

Noninvasive tools (NITs) for predicting varices in children with portal hypertension (PHTN) are infrequently used.

Methods

Eighty-five consecutive, treatment-naïve children with PHTN and 97 controls were enrolled study from July 2017 to November 2018. Each case was evaluated by esophagogastroduodenoscopy (EGD) and various NITs: platelet spleen size Z (PSZ), clinical prediction rule (CPR), King’s variceal prediction rule (KVaPS), Splenic stiffness (SSM) and liver stiffness measurement (LSM) by point shear wave elastrography (pSWE).

Results

Had PHTN due to extra hepatic portal vein obstruction (EHPVO) and 70% due to cirrhosis [chronic liver disease (CLD)]. Sixty-five percent of PHTN cases had varices. Children with varices had lower platelet counts, lower albumin and larger spleens. SSM and LSM were significantly higher in cases as compared with controls. SSM was significantly higher in cases with varices than those without. SSM and LSM, at cutoffs of 3.8 and 3.2 kPa, respectively, discriminated PHTN cases from controls with an area under the curve (AUROC) of 0.67 (0.59–0.74). Both SSM and LSM predicted varices in CLD, but in EHPVO, only SSM predicted varices. SSM of 5.2 and 12.8 kPa, in CLD and EHPVO subgroups, respectively, had AUROC of 0.73 and 0.94 for variceal prediction. Blood-based NITs performed better in the CLD subgroup: aspartate aminotransferase platelet ratio index, CPR and KVPS predicted severity of PHTN with AUROC of 0.81, 0.92 and 0.93, respectively.

Conclusions

Blood-based NITs outperform elastography for prediction of PHTN/varices in children with CLD. SSM by pSWE is a better predictor of varices than LSM, especially in the EHPVO subgroup.
NordiQC Assessments of Keratin 5 Immunoassays
Authors: Thomsen Christian , Nielsen Ole , Nielsen Søren , Røge Rasmus , Vyberg Mogens
Published: April 2020

This paper is number 7 in a series developed through a partnership between ISIMM and NordiQC with the purpose of reporting research assessing the performance characteristics of immunoassays in an external proficiency testing program.
Radial Pronation Angle
Authors: Liu Lu , Liu Chang , Rong Yan-Bo , Bai Fan , Chen Shan-Lin
Published: April 2020

Introduction

Congenital proximal radioulnar synostosis (CPRUS) is a relatively rare forearm deformity that is characterized by a fixed pronated forearm of varying severity. The osseous synostosis between the proximal part of the ulna and the radius can be seen on the X-ray images in most cases. Many researchers have attempted to identify methods to measure the disease severity to guide in the treatment of CPRUS. However, to describe the overall deformity, the use of multiple indicators is essential, and some of these measurements require special software or need to be conducted on cadavers.

Objective

The aim of the current study was to introduce the radius pronation angle (RPA), a novel radiological evaluation index of CPRUS, and analyze the relationship between the RPA and the severity of the deformity.

Methods

Three-dimensional models of 43 CPRUS forearms (19 left forearms and 24 right forearms) of 32 patients (23 males and 9 females; average age was 6 years 8 months; range, from 1.5 to 27 years) treated at Beijing Ji Shui Tan Hospital during 2016 to 2019 were reconstructed using a computer-assisted technique. The special flexed posterior-anterior views of the X-ray image (the f-PA view) of the forearms were obtained, and the forearm rotation angle and the ulnar inner rotation angle were measured on each forearm. The RPA was measured on the f-PA view, and the lengths of the osseous synostosis, ulna, and the radial head were measured on the computed tomography scan images using the multiplanar reconstruction function. The Pearson index was analyzed between the RPA and the other measurements.

Results

The RPAs were correlated with the forearm rotation angle, ulnar inner rotation angle, relative length of the osseous synostosis, and the relative length of the radial head (P < 0.05).

Conclusions

The RPA can be measured quickly and easily on the f-PA view of the X-ray image and can be used as a reliable indicator of the severity of CPRUS.
Comparative Effectiveness of Transversus Abdominis Plane Blocks in Abdominally Based Autologous Breast Reconstruction
Authors: Chi David , Chen Austin D. , Ha Austin Y. , Yaeger Lauren H. , Lee Bernard T.
Published: April 2020

Background

The abdomen is the most common donor site in autologous microvascular free flap breast reconstruction and contributes significantly to postoperative pain, resulting in increased opioid use, length of stay, and hospital costs. Enhanced Recovery After Surgery (ERAS) protocols have demonstrated multiple clinical benefits, but these protocols are widely heterogeneous. Transversus abdominis plane (TAP) blocks have been reported to improve pain control and may be a key driver of the benefits seen with ERAS pathways.

Methods

A systematic review and meta-analysis of studies reporting TAP blocks for abdominally based breast reconstruction were performed. Studies were extracted from 6 public databases before February 2019 and pooled in accordance with the PROSPERO registry. Total opioid use, postoperative pain, length of stay, hospital cost, and complications were analyzed using a random effects model.

Results

The initial search yielded 420 studies, ultimately narrowed to 12 studies representing 1107 total patients. Total hospital length of stay (mean difference, −1.00 days; P < 0.00001; I
2 = 81%) and opioid requirement (mean difference, −133.80 mg of oral morphine equivalent; P < 0.00001; I
2 = 97%) were decreased for patients receiving TAP blocks. Transversus abdominis plane blocks were not associated with any significant differences in postoperative complications (P = 0.66), hospital cost (P = 0.22), and postoperative pain (P = 0.86).

Conclusions

Optimizing postoperative pain management after abdominally based microsurgical breast reconstruction is invaluable for patient recovery. Transversus abdominis plane blocks are associated with a reduction in length of stay and opioid use, representing a safe and reasonable strategy for decreasing postoperative pain.
Assessing Gaze Patterns in Common Cosmetic Procedures With Eye-Tracking Technology
Authors: Peterson Dylan J. , Azad Amee D. , Gkorila Aikaterina , Patel Ashraf A. , Boudreault Molly S. , Nazerali Rahim S.
Published: April 2020

Background

Understanding the salient features that draw focus when assessing aesthetics is important for maximizing perceived outcomes. Eye-tracking technology provides an unbiased method for determining the features that draw attention when evaluating aesthetic plastic surgery. This study aimed to characterize viewing patterns of plastic surgery patients and laypeople when assessing facial cosmetic procedure images.

Methods

Twenty women who previously underwent cosmetic procedures and twenty women without a history of cosmetic procedures were shown sixteen pairs of preprocedure and postprocedure images of patients who underwent laser resurfacing or lip augmentation. Image pairs were randomized to whether preprocedural or postprocedural images came first. Participants viewed each image until they decided upon an aesthetic rating (scored 1–10), while an eye-tracking device recorded participants' gaze.

Results

The patient group's average ratings were 8.2% higher for preprocedural images and 13.3% higher for postprocedural images (P < 0.05 for both). The patient group spent 20.4% less time viewing images but spent proportionally more time evaluating the relevant features of each procedure (41.7% vs 23.3%, P < 0.01), such as the vermillion border of the upper lip, labial commissure, or periorbital region (P < 0.05 for each). For both groups, the most common site of first fixation was the nose for laser resurfacing images (26.6%) and the labial commissure for lip augmentation images (37.7%). Both groups spent more time fixated on nasolabial folds, marionette lines, and the periorbital region when viewing pre–laser resurfacing images than postprocedural images. Overall, each group had similar viewing patterns for time to first fixation on and frequency of fixations for a particular feature.

Conclusions

Women who previously underwent cosmetic procedures view postprocedural images more favorably and require less time to assess images, likely related to familiarity with aesthetic procedures. These women spend more time fixated on relevant features, such as the vermillion border of the upper lip, the labial commissure, and the periorbital region, than the control group. Notably, each group spent less time focused on regions associated with wrinkles, such as the marionette and periorbital areas in post–laser resurfacing images, suggesting that the procedure reduces attention-drawing features in these areas.
Spiribacter aquaticus Leon et al. 2017 is a later heterotypic synonym of Spiribacter roseus Leon et al. 2016. Reclassification of Halopeptonella vilamensis Menes et al. 2016 as Spiribacter vilamensis comb. nov.
Authors: León María José , Galisteo Cristina , Ventosa Antonio , Sánchez-Porro Cristina
Published: April 2020

A comparative taxonomic study of

Spiribacter

and

Halopeptonella

species was carried out using a phylogenomic approach based on comparison of the core genome, orthologous average nucleotide identity (OrthoANIu), Genome-to-Genome Distance Calculator (GGDC) and average amino acid identity (AAI). Phylogenomic analysis based on 976 core translated gene sequences obtained from their genomes showed that

Spiribacter aquaticus

SP30T,

S. curvatus

UAH-SP71T,

S. roseus

SSL50T,

S. salinus

M19-40T and

Halopeptonella vilamensis

DSM 21056T formed a robust cluster, clearly separated from the remaining species of closely related taxa. AAI between

H. vilamensis

DSM 21056T and the species of the genus

Spiribacter

was ≥73.1 %, confirming that all these species belong to the same single genus. On the other hand,

S. roseus

SSL50T and

S. aquaticus

SP30T showed percentages of OrthoANIu and digital DNA–DNA hybridization of 98.4 % and 85.3 %, respectively, while these values among those strains and the type strains of the other species of

Spiribacter

and

H. vilamensis

DSM 21056T were ≤80.8 and 67.8 %, respectively. Overall, these data show that

S. roseus

SSL50T and

S. aquaticus

SP30T constitute a single species and thus that

S. aquaticus

SP30T should be considered as a later, heterotypic synonym of

S. roseus

SSL50T based on the rules for priority of names. We propose an emended description of

S. roseus

, including the features of

S. aquaticus

. We also propose the reclassification of

H. vilamensis

as Spiribacter vilamensis comb. nov.
Molecular determinants of β-arrestin coupling to formoterol-bound β1-adrenoceptor
Authors: Lee Yang , Warne Tony , Nehmé Rony , Pandey Shubhi , Dwivedi-Agnihotri Hemlata , Edwards Patricia C. , García-Nafría Javier , Leslie Andrew G.W. , Shukla Arun K. , Tate Christopher G.
Published: April 2020

The β1-adrenoceptor (β1AR) is a G protein-coupled receptor (GPCR) activated by the hormone noradrenaline, resulting in the coupling of the heterotrimeric G protein Gs1. G protein-mediated signalling is terminated by phosphorylation of the receptor C-terminus and coupling of β-arrestin 1 (βarr1, also known as arrestin-2), which displaces Gsand induces signalling through the MAP kinase pathway2. The ability of synthetic agonists to induce signalling preferentially through either G proteins or arrestins (biased agonism)3is important in drug development, as the therapeutic effect may arise from only one signalling cascade, whilst the other pathway may mediate undesirable side effects4. To understand the molecular basis for arrestin coupling, we determined the electron cryo-microscopy (cryo-EM) structure of the β1AR-βarr1 complex in lipid nanodiscs bound to the biased agonist formoterol5, and the crystal structure of formoterol-bound β1AR coupled to the G protein mimetic nanobody Nb806. βarr1 couples to β1AR in a distinct manner to how Gscouples to β2AR7, with the finger loop of βarr1 occupying a narrower cleft on the intracellular surface closer to transmembrane helix H7 than the C-terminal α5 helix of Gs. The conformation of the finger loop in βarr1 is different from that adopted by the finger loop in visual arrestin when it couples to rhodopsin8, and its β-turn configuration is reminiscent of the loop in Nb80 that inserts at the same position. β1AR coupled to βarr1 showed significant differences in structure compared to β1AR coupled to Nb80, including an inward movement of extracellular loop 3 (ECL3) and the cytoplasmic ends of H5 and H6. In the orthosteric binding site there was also weakening of interactions between formoterol and the residues Ser2115.42and Ser2155.46, and a reduction in affinity of formoterol for the β1AR-βarr1 complex compared to β1AR coupled to mini-Gs. These differences provide a foundation for the development of small molecules that could bias signalling in the β-adrenoceptors.
Forecasting COVID-19 impact in India using pandemic waves Nonlinear Growth Models
Authors: Kumar Pavan , Singh Ram Kumar , Nanda Chintan , Kalita Himangshu , Patairiya Shashikanta , Sharma Yagya Datt , Rani Meenu , Bhagavathula Akshaya Srikanth
Published: April 2020

The ongoing pandemic of the coronavirus disease 2019 (COVID-19) started in China and devastated a vast majority of countries. In India, COVID-19 cases are steadily increasing since January 30, 2020, and the government-imposed lockdown across the country to curtail community transmission. COVID-19 forecasts have played an important role in capturing the probability of infection and the basic reproduction rate. In this study, we predicted some trajectories of trajectories associated with COVID-19 in the coming days in India using an Auto-regression integrated moving average model (ARIMA) and Richard’s model. By the end of April 2020, the incidence of new cases is predicted to be 5200 (95% CI: 4650 to 6002) through the ARIMA model versus be 6378 (95% CI: 4904 to 7851) Richard model. We estimated that there would be a total of 197 (95% CI: 118 to 277) deaths and drop down in the recovery rates will reach around 501 (95% CI: 245 to 758) by the end of April 2020. These estimates can help to strengthen the implementation of strategies to increase the health system capacity and enactment of social distancing measures all over India.
Identification of a common deletion in the spike protein of SARS-CoV-2
Authors: Liu Zhe , Zheng Huanying , Yuan Runyu , Li Mingyue , Lin Huifang , Peng Jingju , Xiong Qianlin , Sun Jiufeng , Li Baisheng , Wu Jie , Hulswit Ruben J.G. , Bowden Thomas A. , Rambaut Andrew , Loman Nick , Pybus Oliver G , Ke Changwen , Lu Jing
Published: April 2020

Two notable features have been identified in the SARS-CoV-2 genome: (1) the receptor binding domain of SARS-CoV-2; (2) a unique insertion of twelve nucleotide or four amino acids (PRRA) at the S1 and S2 boundary. For the first feature, the similar RBD identified in SARs-like virus from pangolin suggests the RBD in SARS-CoV-2 may already exist in animal host(s) before it transmitted into human. The left puzzle is the history and function of the insertion at S1/S2 boundary, which is uniquely identified in SARS-CoV-2. In this study, we identified two variants from the first Guangdong SARS-CoV-2 cell strain, with deletion mutations on polybasic cleavage site (PRRAR) and its flank sites. More extensive screening indicates the deletion at the flank sites of PRRAR could be detected in 3 of 68 clinical samples and half of 22 in vitro isolated viral strains. These data indicate (1) the deletion of QTQTN, at the flank of polybasic cleavage site, is likely benefit the SARS-CoV-2 replication or infection in vitro but under strong purification selection in vivo since it is rarely identified in clinical samples; (2) there could be a very efficient mechanism for deleting this region from viral genome as the variants losing 23585-23599 is commonly detected after two rounds of cell passage. The mechanistic explanation for this in vitro adaptation and in vivo purification processes (or reverse) that led to such genomic changes in SARS-CoV-2 requires further work. Nonetheless, this study has provided valuable clues to aid further investigation of spike protein function and virus evolution. The deletion mutation identified in vitro isolation should be also noted for current vaccine development.
Neuroanatomy and Behaviour in Mice with a Haploinsufficiency of AT-Rich Interactive Domain 1B (ARID1B) Throughout Development
Authors: Ellegood J. , Petkova S.P. , Kinman A. , Qiu L.R. , Wade A. , Fernandes D. , Lindenmaier Z. , Crieghton A. , Nutter L. , Nord A.S. , Silverman J.L. , Lerch J.P.
Published: April 2020

One of the causal mechanisms underlying neurodevelopmental disorders (NDDs) is chromatin modification, and genes that regulate chromatin modify and control events regulating the formation of neural connections. AT-Rich Interactive Domain 1B(ARID1B), a chromatin modifier, has been shown to be reduced in autism spectrum disorder (ASD) and to affect rare and inherited genetic variation in a broad set of NDDs. For this work, a novel preclinical mouse model ofArid1bdeficiency was created and molecularly validated to characterize and define neuroanatomical, behavioural and transcriptional phenotypes. Brains of adultArid1b+/-mice had a smaller cerebellum along with a larger hippocampus and corpus callosum. In addition, a notable sex dependence was observed throughout development; males had an early emergence of the neuroanatomical phenotype around postnatal day 7, whereas females had a delayed emergence of the phenotype around postnatal day 40. Behavioural assays relevant to NDD were conducted during neonatal development and adulthood to evaluate general health, anxiety-like, motor, cognitive, and social behaviours inArid1b+/-mice. During neonatal development,Arid1b+/-mice exhibited robust impairments in ultrasonic vocalizations (USVs) and metrics of developmental growth. As adults,Arid1b+/-mice showed low motor skills in open field exploration and normal three chambered approach.Arid1b+/-mice had learning and memory deficits in novel object recognition but surprisingly not in visual discrimination and reversal touchscreen tasks. Social interactions in the male-female social dyad with USVs revealed social deficits on some but not all parameters. No repetitive behaviours were observed. This study represents a full investigation ofArid1b+/-haploinsufficiency throughout development and highlights the importance of examining both sexes throughout development in NDDs.
Perceptual decisions and oculomotor responses rely on temporally distinct streams of evidence
Authors: Lisi Matteo , Morgan Michael J. , Solomon Joshua A.
Published: April 2020

Perceptual decisions often require the integration of noisy sensory evidence over time. This process is formalized with sequential sampling models, where evidence is accumulated up to a decision threshold before a choice is made. Although intuition suggests that decision formation must precede the preparation of a motor response (i.e., the action used to communicate the choice), neurophysiological findings have suggested that these two processes might be one and the same. To test this idea, we developed a reverse-correlation protocol in which the visual stimuli that influence decisions can be distinguished from those guiding motor responses. In three experiments, we found that the temporal weighting function of oculomotor responses did not overlap with the relatively early weighting function of stimulus properties having an impact on decision formation. These results support a timeline in which perceptual decisions are formed, at least in part, prior to the preparation of a motor response.
Virus-host interactome and proteomic survey of PMBCs from COVID-19 patients reveal potential virulence factors influencing SARS-CoV-2 pathogenesis
Authors: Li Jingjiao , Guo Mingquan , Tian Xiaoxu , Liu Chengrong , Wang Xin , Yang Xing , Wu Ping , Xiao Zixuan , Qu Yafei , Yin Yue , Fu Joyce , Zhu Zhaoqin , Liu Zhenshan , Peng Chao , Zhu Tongyu , Liang Qiming
Published: April 2020

The ongoing coronavirus disease (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a global public health concern due to relatively easy person-to-person transmission and the current lack of effective antiviral therapy. However, the exact molecular mechanisms of SARS-CoV-2 pathogenesis remain largely unknown. We exploited an integrated proteomics approach to systematically investigate intra-viral and virus-host interactomes for the identification of unrealized SARS-CoV-2 host targets and participation of cellular proteins in the response to viral infection using peripheral blood mononuclear cells (PBMCs) isolated from COVID-19 patients. Using this approach, we elucidated 251 host proteins targeted by SARS-CoV-2 and more than 200 host proteins that are significantly perturbed in COVID-19 derived PBMCs. From the interactome, we further identified that non-structural protein nsp9 and nsp10 interact with NKRF, a NF-КB repressor, and may precipitate the strong IL-8/IL-6 mediated chemotaxis of neutrophils and overexuberant host inflammatory response observed in COVID-19 patients. Our integrative study not only presents a systematic examination of SARS-CoV-2-induced perturbation of host targets and cellular networks to reflect disease etiology, but also reveals insights into the mechanisms by which SARS-CoV-2 triggers cytokine storms and represents a powerful resource in the quest for therapeutic intervention.
Cell cycle abnormality is a cellular phenotype in OCD
Authors: Manjappa Pravallika , Balachander Srinivas , Naaz Safoora , Nadella Ravi Kumar , Shukla Tulika , Paul Pradip , Purushottam Meera , Reddy YC Janardhan , Jain Sanjeev , Viswanath Biju , Sud Reeteka
Published: April 2020

Abnormal indices of cell cycle regulation have been reported in multiple psychiatric disorders. Though reports specific to obsessive compulsive disorder (OCD) are scant, numerous studies have highlighted partly common underlying biology in psychiatric disorders, cell cycle regulation being one such process. In this study, we therefore aimed to explore cell cycle in OCD. To the best of our knowledge, this is the first study to investigate these effects in OCD. We also evaluated the effect of in vitro fluoxetine, commonly used serotonin reuptake inhibitor (SRI) in OCD patients, on cell cycle regulation. The effects of both disease (OCD) and treatment (SRI) were assessed using lymphoblastoid cell lines (LCLs), derived from OCD patients and healthy controls, as a model system. LCLs were treated with 10μM of fluoxetine for 24 hours, and the percentage of cells in each phase of the cell cycle was determined by flow cytometry. We observed a lower proportion of cells in the G2/M phase in OCD cases than controls. The findings suggest that cell cycle dysregulation could be peripheral cellular phenotype for OCD. Among cases, all of whom had been systematically characterized for SRI treatment response, LCLs from non-responders to SRI treatment had a lower proportion of cells in G2/M phase than responders.
Ambient nitrogen dioxide pollution and spread ability of COVID-19 in Chinese cities
Authors: Yao Ye , Pan Jinhua , Liu Zhixi , Meng Xia , Wang Weidong , Kan Haidong , Wang Weibing
Published: April 2020

The Coronavirus (COVID-19) epidemic, which was first reported in December 2019 in Wuhan, China, has caused 219,331 confirmed cases as of 20 March 2020, with 81,301 cases being reported in China. It has been declared a pandemic by the World Health Organization in 11 March 2020 (1). Although massive intervention measures have been implemented in China (e.g. shutting down cities, extending holidays and travel ban) and many other countries, the spread of the disease are unlikely to be stopped over the world shortly. It is becoming evident that environmental factors are associated with seasonality of respiratory-borne diseases’ epidemics (2). Previous studies have suggested that ambient nitrogen dioxide (NO2) exposure may play a role in the phenotypes of respiratory diseases, including, but not limited to, influenza, asthma and severe acute respiratory syndrome (SARS). NO2), for example, might increase the susceptibility of adults to virus infections (3). High exposure to NO2 before the start of a respiratory viral infection is associated with the severity of asthma exacerbation (4). This study aims to assess the associations of ambient NO2 levels with spread ability of COVID-19 across 63 Chinese cities, and provides information for the further prevention and control of COVID-19.
Comparing performance of deep convolutional neural network with orthopaedic surgeons on identification of total hip prosthesis design from plain radiographs
Authors: Borjali Alireza , Chen Antonia F. , Bedair Hany S. , Melnic Christopher M. , Muratoglu Orhun K. , Morid Mohammad A. , Varadarajan Kartik M.
Published: April 2020

A crucial step in preoperative planning for a revision total hip replacement (THR) surgery is accurate identification of failed implant design, especially if one or more well-fixed/functioning components are to be retained. Manual identification of the implant design from preoperative radiographic images can be time-consuming and inaccurate, which can ultimately lead to increased operating room time, more complex surgery, and increased healthcare costs. No automated system has been developed to accurately and efficiently identify THR implant designs. In this study, we present a novel, fully automatic and interpretable approach to identify the design of nine different THR femoral implants from plain radiographs using deep convolutional neural network (CNN). We also compared the CNN’s performance with three board-certified and fellowship trained orthopaedic surgeons. The CNN achieved on-par accuracy with the orthopaedic surgeons while being significantly faster. The need for additional training data for less distinct designs was also highlighted. Such CNN can be used to automatically identify the design of a failed THR femoral implant preoperatively in just a fraction of a second, saving time and improving identification accuracy.
A Gaussian model for the time development of the Sars-Cov-2 corona pandemic disease. Predictions for Germany made on March 30, 2020
Authors: Schlickeiser R. , Schlickeiser F.
Published: April 2020

For Germany it is predicted that the first wave of the corona pandemic disease reaches its maximum of new infections on April 11th, 2020days with 90 percent confidence. With a delay of about 7 days the maximum demand on breathing machines in hospitals occurs on April 18th, 2020days. The first pandemic wave ends in Germany end of May 2020. The predictions are based on the assumption of a Gaussian time evolution well justified by the central limit theorem of statistics. The width and the maximum time and thus the duration of this Gaussian distribution are determined from a statisticalχ2-fit to the observed doubling times before March 28, 2020.
A hybrid cytcmaturation system enhances the bioelectrical performance of engineeredEscherichia coliby improving the rate-limiting step
Authors: Su Lin , Fukushima Tatsuya , Ajo-Franklin Caroline M.
Published: April 2020

Bioelectronic devices can use electron flux to enable communication between biotic components and abiotic electrodes. We have modifiedEscherichia colito electrically interact with electrodes by expressing the cytochromecfromShewanella oneidensisMR-1. However, we observe inefficient electrical performance, which we hypothesize is due to the limited compatibility of theE. colicytochromecmaturation (Ccm) systems with MR-1 cytochromec. Here we test whether the bioelectronic performance ofE. colican be improved by constructing hybrid Ccm systems containing protein domains from bothE. coliandS. oneidensisMR-1. The hybrid CcmH increased cytochromecexpression by increasing the abundance of CymA 60%, while only slightly changing the abundance of the other cytochromesc. Electrochemical measurements showed that the overall current from the hybridccmstrain increased 121% relative to the wildtypeccmstrain, with an electron flux per cell of 12.3 ± 0.3 fA·cell-1. Additionally, the hybridccmstrain doubled its electrical response with the addition of exogenous flavin, and quantitative analysis of this demonstrates CymA is the rate-limiting step in this electron conduit. These results demonstrate that this hybrid Ccm system can enhance the bioelectrical performance of the cytcexpressingE. coli, allowing the construction of more efficient bioelectronic devices.
Precursor intensity-based label-free quantification software tools for proteomic and multiomic analysis within the Galaxy Platform
Authors: Mehta Subina , Easterly Caleb , Sajulga Ray , Millikin Robert J. , Argentini Andrea , Eguinoa Ignacio , Martens Lennart , Shortreed Michael R. , Smith Lloyd M. , McGowan Thomas , Kumar Praveen , Johnson James E. , Griffin Timothy J. , Jagtap Pratik
Published: April 2020

For mass spectrometry-based peptide and protein quantification, label-free quantification (LFQ) based on precursor mass peak (MS1) intensities is considered reliable due to its dynamic range, reproducibility, and accuracy. In LFQ workflows, protein abundance changes are inferred from peptide-level information, including microbial peptides (for metaproteomics) and peptides carrying post-translational modifications (for proteomics) and/or variant sequences (for proteogenomics). Multi-omics studies (such as proteogenomics and metaproteomics) rely on peptide detection and quantification to identify and quantify peptides that map to unique proteoforms and metaproteins. The Galaxy for proteomics (Galaxy-P) platform has proven useful for the development of accessible workflows to identify proteins in these complex multi-omic studies. However, proteomics workflows within the Galaxy platform have lacked well-tested label-free quantification tools.

In this study, our main goals were to evaluate two recently published open-source LFQ tools and to implement them within the Galaxy platform, enabling their easy integration with established workflows. These two tools, moFF and FlashLFQ, were selected based on their described peptide quantification capabilities and amenability to Galaxy implementation. Through rigorous testing and communication with the tools’ developers, we gained insights into the software features necessary for maximizing the performance of each tool. Software features evaluated included: a) match-between-runs (MBR); b) using both Thermo .raw and HUPO standards .mzML file formats as input for improved quantification; c) use of containers and/or conda packages; d) parameters needed for analyzing large input datasets; and e) optimization and validation of software performance. This work 1) establishes a process for software implementation, optimization and validation within Galaxy; and 2) makes powerful new tools for LFQ available which should prove highly useful for a variety of proteomics and multi-omics applications employing the Galaxy platform.
Discovery of a hidden transient state in all bromodomain families
Authors: Raich Lluís , Meier Katharina , Günther Judith , Christ Clara D. , Noé Frank , Olsson Simon
Published: April 2020

Bromodomains (BDs) are small protein modules that interact with acetylated marks in histones. These post-translational modifications are pivotal to regulate gene expression, making BDs promising targets to treat several diseases. While the general structure of BDs is well known, their dynamical features and their interplay with other macromolecules are poorly understood, hampering the rational design of potent and selective inhibitors. Here we combine extensive molecular dynamics simulations, Markov state modeling and structural data to reveal a novel and transiently formed state that is conserved across all BD families. It involves the breaking of two backbone hydrogen bonds that anchor the ZA-loop with the αAhelix, opening a cryptic pocket that partially occludes the one associated with histone binding. Our results suggest that this novel state is an allosteric regulatory switch for BDs, potentially related to a recently unveiled BD-DNA binding mode.
Modelling the spatial crosstalk between two biochemical signals explains wood formation dynamics and tree-ring structure
Authors: Hartmann Félix P. , Rathgeber Cyrille B. K. , Badel Eric , Fournier Meriem , Moulia Bruno
Published: April 2020

In conifers, xylogenesis produces during a growing season a very characteristic tree-ring structure: large thin-walled earlywood cells followed by narrow thick-walled latewood cells. Although many factors influence the dynamics of differentiation and the final dimensions of xylem cells, the associated patterns of variation remain very stable from one year to the next. While radial growth is characterised by an S-shaped curve, the widths of xylem differentiation zones exhibit characteristic skewed bell-shaped curves. These elements suggest a strong internal control of xylogenesis. It has long been hypothesised that much of this regulation relies on a morphogenetic gradient of auxin. However, recent modelling works have shown that while this hypothesis could account for the dynamics of stem radial growth and the zonation of the developing xylem, it failed to reproduce the characteristic tree-ring structure. Here we investigated the hypothesis of a regulation by a crosstalk between auxin and a second biochemical signal, using dynamical modelling. We found that, in conifers, such a crosstalk is sufficient to simulate the characteristic features of wood formation dynamics, as well as the resulting tree-ring structure. In this model, auxin controls cell enlargement rates while another signal (e.g., cytokinin, TDIF) drives cell division and auxin polar transport.

Highlight

A dynamical model proves that two interacting signals (auxin, plus a cytokinin or the TDIF peptide) can drive wood formation dynamics and tree-ring structure development in conifers.
Feminisation of complex traits inDrosophila melanogastervia female-limited X chromosome evolution
Authors: Lund-Hansen Katrine K. , Abbott Jessica K. , Morrow Edward H.
Published: April 2020

A handful of studies have investigated sexually antagonistic constraints on obtaining sex-specific fitness optima, though exclusively through male-genome-limited evolution experiments. In this paper, we established a female-limited X chromosome evolution experiment, where we used an X chromosome balancer to enforce the inheritance of the X chromosome through the matriline, thus removing exposure to male selective constraints. This approach eliminates the effects of sexually antagonistic selection on the X chromosome, permitting evolution towards a single sex-specific optimum. After multiple generations of selection, we found strong evidence that body size and development time had moved towards a female-specific optimum, whereas reproductive fitness and locomotion activity remained unchanged. The changes in body size and development time are consistent with previous results, and suggest that the X chromosome is enriched for sexually antagonistic genetic variation controlling these traits. The lack of change in reproductive fitness and locomotion activity could be due to a number of mutually non-exclusive explanations, including a lack of sexually antagonistic variance on the X chromosome or confounding effects of the use of the balancer chromosome. This study is the first to employ female-genome-limited selection and adds to the understanding of the complexity of sexually antagonistic genetic variation.
Prion infection, transmission and cytopathology modelled in a low-biohazard human cell line
Authors: Avar Merve , Heinzer Daniel , Steinke Nicolas , Doğançay Berre , Moos Rita , Lugan Severine , Cosenza Claudia , Hornemann Simone , Andréoletti Olivier , Aguzzi Adriano
Published: April 2020

Transmission of prion infectivity to susceptible murine cell lines has simplified prion titration assays and has greatly reduced the need for animal experimentation. However, murine cell models suffer from technical and biological constraints. Human cell lines might be more useful, but they are much more biohazardous and are often poorly infectible. Here we describe the human clonal cell line hovS, which lacks the humanPRNPgene and expresses instead the ovinePRNPVRQ allele. HovS cells were highly susceptible to the PG127 strain of sheep-derived murine prions, reaching up to 90% infected cells in any given culture, and were maintained in a continuous infected state for at least 14 passages. Infected hovS cells produced proteinase K-resistant prion protein (PrPSc), pelletable PrP aggregates andbona fideinfectious prions capable of infecting further generations of naïve hovS cells and mice expressing the VRQ allelic variant of ovine PrPC. Infection in hovS led to prominent cytopathic vacuolation akin to the spongiform changes observed in individuals suffering from prion diseases. In addition to expanding the toolbox for prion research to human experimental genetics, the hovS cell line provides a human-derived system that does not require human prions. Hence, the manipulation of scrapie-infected hovS cells may present fewer biosafety hazards than that of genuine human prions.
Dopaminergic signalling modulates reward-driven music memory consolidation
Authors: Ferreri Laura , Mas-Herrero Ernest , Cardona Gemma , Zatorre Robert J. , Antonijoan Rosa M. , Valle Marta , Riba Jordi , Ripollés Pablo , Rodriguez-Fornells Antoni
Published: April 2020

Previously, we providedcausalevidence for a dopamine-dependent effect of intrinsic reward on memory during self-regulated learning (Ripollés et al., 2016; Ripollés et al., 2018). Here, we further investigated the dopamine-dependent link between reward and memory by focusing on one of the most iconicabstractrewards in humans: music. Twenty-nine healthy participants listened to unfamiliar excerpts—which had to be remembered following a consolidation period—after the intake of a dopaminergic antagonist, a dopaminergic precursor, and a placebo across three separated sessions. The intervention modulated the pleasantness experienced during music-listening and memory recognition of the presented songs (i.e., lower with the antagonist, higher with the precursor) in individuals with higher sensitivity to musical reward. Our work highlights the flexibility of the human dopaminergic system, which is able to enhance memory formation not only through explicit and/or primary reinforcers but also via intrinsic, abstract, or aesthetic rewards of different natures.
A high-density human mitochondrial proximity interaction network
Authors: Antonicka Hana , Lin Zhen-Yuan , Janer Alexandre , Weraarpachai Woranontee , Gingras Anne-Claude , Shoubridge Eric A.
Published: April 2020

We used BioID, a proximity-dependent biotinylation assay, to interrogate 100 mitochondrial baits from all mitochondrial sub-compartments to create a high resolution human mitochondrial proximity interaction network. We identified 1465 proteins, producing 15626 unique high confidence proximity interactions. Of these, 528 proteins were previously annotated as mitochondrial, nearly half of the mitochondrial proteome defined by Mitocarta 2.0. Bait-bait analysis showed a clear separation of mitochondrial compartments, and correlation analysis among preys across all baits allowed us to identify functional clusters involved in diverse mitochondrial functions, and to assign uncharacterized proteins to specific modules. We demonstrate that this analysis can assign isoforms of the same mitochondrial protein to different mitochondrial sub-compartments, and show that some proteins may have multiple cellular locations. Outer membrane baits showed specific proximity interactions with cytosolic proteins and proteins in other organellar membranes, suggesting specialization of proteins responsible for contact site formation between mitochondria and individual organelles. This proximity network will be a valuable resource for exploring the biology of uncharacterized mitochondrial proteins, the interactions of mitochondria with other cellular organelles, and will provide a framework to interpret alterations in sub-mitochondrial environments associated with mitochondrial disease.

Bullet points

We created a high resolution human mitochondrial protein proximity map using BioID

Bait-bait analysis showed that the map has sub-compartment resolution and correlation analysis of preys identified functional clusters and assigned proteins to specific modules

We identified isoforms of matrix and IMS proteins with multiple cellular localizations and an endonuclease that localizes to both the matrix and the OMM

OMM baits showed specific interactions with non-mitochondrial proteins reflecting organellar contact sites and protein dual localization