bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-world outcomes associated with standard half-life and extended half-life factor replacement products for treatment of haemophilia A and B
Authors: Chhabra Amit , Spurden Dean , Fogarty Patrick F. , Tortella Bartholomew J. , Rubinstein Emily , Harris Simon , Pleil Andreas M. , Mellor Jennifer , de Courcy Jonathan , Alvir José
Published: April 2020

Standard-of-care treatment for haemophilia A or B is to maintain adequate coagulation factor levels through clotting factor administration. The current study aimed to evaluate annualised bleeding rates (ABR) and treatment adherence for haemophilia A or B patients receiving standard half-life (SHL) vs. extended half-life (EHL) factor replacement products. We analysed data from the Adelphi Disease-Specific Programmes, a health record–based survey of United States and European haematologists. Analysis included 651 males with moderate-to-severe haemophilia A or B (the United States, n = 132; Europe, n = 519). The haemophilia A analysis included 501 patients (SHL, n = 435; EHL, n = 66). In the combined United States/European population, mean (SD) ABR was 1.7 (1.69) for the SHL group and 1.8 (2.00) for the EHL group. A total of 72% of patients receiving SHL factor VIII and 75% of patients receiving EHL factor VIII in the combined population were fully adherent (no doses missed of the last 10 doses), as reported by physicians. The haemophilia B analysis included 150 patients (SHL, n = 114; EHL, n = 36). The mean (SD) ABR in the combined population was 2.1 (2.16) for patients receiving SHL factor IX (FIX) and 1.4 (1.48) for patients receiving EHL FIX. The percentage of fully adherent patients (physician-reported) was similar in both treatment groups (SHL FIX, 68%; EHL FIX, 73%). In this preliminary real-world survey in a relatively small sample of patients, measures of ABR and adherence between SHL and EHL products were evaluated. Additional real-world research on prescribing patterns, SHL vs. EHL effectiveness, and adherence is warranted.
Photoreceptor assessment in focal laser-treated central serous chorioretinopathy using adaptive optics and fundus autofluorescence
Authors: Ochinciuc Radu , Ochinciuc Uliana , Stanca Horia T. , Barac Ramona , Darabus Diana , Şuţă Marius , Baltă Florian , Burcea Marian
Published: April 2020

This study analyzed cone density, cone mosaic, and fundus autofluorescence (FAF) images in patients with focal laser-treated central serous chorioretinopathy (CSC).

Observational case series.

Forty-two eyes of 21 patients with unilateral treated CSC and bilateral best-corrected visual acuity of 1.0 (decimal fraction) were included. FAF and cone mosaic images were obtained in all patients with an adaptive optics fundus camera. Densities were recorded at 20 points throughout the macula, and choroidal thicknesses were measured.

Mean choroidal thicknesses were 419.95 ± 110.33 μm in normal eyes, 459.09 ± 90.07 μm in eyes with active CSC, and 438.61 ± 107.57 μm in treated eyes. The highest density of cones in healthy eyes was 38146 cones/mm2, with a 5.66-μm intercellular space (IS), at 700 μm temporal to the center. In eyes with treated CSC, the highest density was 32749 cones/mm2, with a 6.13-μm IS, at 500 μm nasal to the center. In all quadrants, median values of maximum cone density were significantly higher in healthy eyes (P = .02,P = .003,P = .0001, andP = .001). Three types of lesions were identified on FAF and were correlated with those on cone mosaic images. Strong correlations were detected between the presence of hypoautofluorescent lesions on the first FAF image and a greater difference between maximum values of photoreceptor density (r2 = 0.46,P = .03), as well as between the presence of hypoautofluorescent lesions and the duration of pathology (r2 = 0.68,P < .001).

The presence of hypoautofluorescent lesions and the duration of pathology were negative prognostic factors in CSC. Laser treatment could prevent photoreceptor loss.
Clinical and sonographic features of nipple lesions
Authors: Cai Siman , Wang Hongyan , Zhu Qingli , Li Jianchu , Sun Qiang , Jiang Yuxin
Published: April 2020

Background:

The aim of this study was to present several cases of benign and malignant nipple lesions and contribute to diagnosis and differential diagnosis.

Methods:

A retrospective study was conducted on 13 patients. All of the patients were evaluated by ultrasonography, and 11 of them had pathological results. We analyzed the clinical and sonographic features.

Results:

There were 3 malignant lesions, 7 benign lesions, and 3 congenital nipple dysplasia, listed as follows:

Malignant lesions (n = 3, 23%): Paget's disease (PD, n = 3, 23%). All of the patients with PD showed unilateral nipple erosion, discharge, and pain. The ultrasound showed abundant blood flow (n = 3, 23%); 2 patients (n = 2, 15%) had microcalcifications.

Benign lesions (n = 7, 54%): Adenoma of the nipple (n = 2, 15%). One patient (n = 1, 8%) had nipple erosion and discharge. Two patients (n = 2, 15%) had a palpable nodule in the nipple. The ultrasound of both patients (n = 2, 15%) showed regular-shaped, clear border nodule with abundant blood flow (n = 2, 15%).

Leiomyoma of the nipple (n = 1, 8%): This male patient was characterized by unilateral nipple enlargement and pain. The ultrasound showed a regular nodule with absent blood flow.

Plasma cell mastitis (n = 2, 15%): Two patients showed unilateral nipple inversion and pain. One patient (n = 1, 8%) showed swollen and redness. The 2 patients showed a lesion in the gland around the nipple present as an irregular shape and unclear boundary hypoechoic mass.

Nipple wart (n = 2, 15%): Two patients showed a unilateral soft exogenous neoplasm. Both of the patients showed a hypoechoic wart; the echo was similar to the nipple, the border was clear, and had no blood flow in the wart.

Nipple Dysplasia (n = 3, 23%): Accessory nipple (n = 3, 23%). Two patients (n = 2, 15%) had accessory nipples in the subcoastal area, 1 patient (n = 1, 8%) in the areolar. All of the patients’ sonographic features were the same as the nipple.

The positive predict value (PPV) of the clinical symptoms: Erosion and discharge are both 75% (P < 0.05). The PPV of the US manifestations: irregular shape, indictinct margin, abundant blood flow, microcalcification, thicken skin in diagnosing malignant lesions are 60%,60%,60%,100%,100%, respectively (P < 0.05).

Conclusions:

The characteristic sonographic features together with clinical symptoms contribute to the diagnosis of nipple lesions.
The utilization of an overground robotic exoskeleton for gait training during inpatient rehabilitation—single-center retrospective findings
Authors: Swank Chad , Trammell Molly , Bennett Monica , Ochoa Christa , Callender Librada , Sikka Seema , Driver Simon
Published: April 2020

Overground robotic exoskeleton gait training is increasingly utilized during inpatient rehabilitation yet without clear guidelines. We describe clinical characteristics associated with robotic exoskeleton gait training and examine outcomes of people with spinal cord injury and stroke who completed usual rehabilitation care with or without robotic exoskeleton gait training. Retrospective review of medical records over a 36 months period. Inpatients with spinal cord injury or stroke and ≥1 robotic exoskeleton gait training session were included. After obtaining a complete list of robotic exoskeleton gait training participants, medical records were reviewed for comparable matches as determined by gait functional independence measure score <4, age 18–100 years, meeting exoskeleton manufacturer eligibility criteria, and participating in usual care only. Functional independence measure was collected on all patients. For spinal cord injury, we collected the walking index for spinal cord injury II. For stroke, we collected the Stroke Rehabilitation Assessment of Movement Measure. Fifty-nine people with spinal cord injury (n = 31 robotic exoskeleton gait training; n = 28 usual care) and 96 people post-stroke (n = 44 robotic exoskeleton gait training; n = 52 usual care) comprised the medical record review. Fifty-eight percent of patients with spinal cord injury and 56% of patients post-stroke completed 5+ robotic exoskeleton gait training sessions and were included in analyses. Robotic exoskeleton gait training dosage varied between our patients with spinal cord injury and patients post-stroke. Robotic exoskeleton gait training utilization during inpatient rehabilitation required consideration of unique patient characteristics impacting functional outcomes. Application of robotic exoskeleton gait training across diagnoses may require different approaches during inpatient rehabilitation.
Nursing Support During Latent Phase Labor
Authors: Breman Rachel Blankstein , Neerland Carrie
Published: April 2020

Purpose:

The purpose of this scoping review was to synthesize the literature on nursing support during the latent phase of the first stage of labor. In 2014, the definition of the beginning of active labor changed from 4 centimeters (cm) to 6 cm cervical dilation. More women may have an induction of labor based on results of recent research showing no causal increase in risk of cesarean birth with elective induction of labor for low-risk nulliparous women. Therefore, in-hospital latent phase labor may be longer, increasing the need for nursing support.

Design:

Scoping review of the literature from 2009 to present.

Methods:

We conducted the review using key words in PubMed, CINAHL, and Scopus. Search terms included different combinations of “latent or early labor,” “birth,” “support,” “nursing support,” “obstetrics,” and “onset of labor.” Peer-reviewed research and quality improvement articles from 2009 to present were included if they had specific implications for nursing care during the latent phase of labor. Articles were excluded if they were not specific to nursing, focused exclusively on tool development, or were from the perspective of pregnant women or providers only.

Results:

Ten articles were included. Results were synthesized into six categories; support of physiologic labor and birth, the nurse's own personal view of labor, birth environment, techniques and tools, decision-making, and importance of latent labor discussion during the prenatal period.

Clinical Implications:

Support for physiologic labor and birth is an important consideration for use of nonpharmacological methods during latent labor. The nurse's own personal view on labor support can influence the support that laboring women receive. Nurses may need additional education on labor support methods.
Associations of Total, Cognitive/Affective, and Somatic Depressive Symptoms and Antidepressant Use With Cardiovascular Disease–Relevant Biomarkers in HIV: Veterans Aging Cohort Study
Authors: Stewart Jesse C. , Polanka Brittanny M. , So-Armah Kaku A. , White Jessica R. , Gupta Samir K. , Kundu Suman , Chang Chung-Chou H. , Freiberg Matthew S.
Published: April 2020

Objective

We sought to determine the associations of total, cognitive/affective, and somatic depressive symptoms and antidepressant use with biomarkers of processes implicated in cardiovascular disease in HIV (HIV-CVD).

Methods

We examined data from 1546 HIV-positive and 843 HIV-negative veterans. Depressive symptoms were assessed using the Patient Health Questionnaire-9, and past-year antidepressant use was determined from Veterans Affair pharmacy records. Monocyte (soluble CD14 [sCD14]), inflammatory (interleukin-6 [IL-6]), and coagulation (D-dimer) marker levels were determined from previously banked blood specimens. Linear regression models with multiple imputation were run to estimate the associations between depression-related factors and CVD-relevant biomarkers.

Results

Among HIV-positive participants, greater somatic depressive symptoms were associated with higher sCD14 (exp[b] = 1.02, 95% confidence interval [CI] = 1.00–1.03) and D-dimer (exp[b] = 1.06, 95% CI = 1.00–1.11) after adjustment for demographics and potential confounders. Further adjustment for antidepressant use and HIV factors slightly attenuated these relationships. Associations were also detected for antidepressant use, as selective serotonin reuptake inhibitor use was related to lower sCD14 (exp[b] = 0.95, 95% CI = 0.91–1.00) and IL-6 (exp[b] = 0.86, 95% CI = 0.76–0.96), and tricyclic antidepressant use was related to higher sCD14 (exp[b] = 1.07, 95% CI = 1.03–1.12) and IL-6 (exp[b] = 1.14, 95% CI = 1.02–1.28). Among HIV-negative participants, total, cognitive/affective, and somatic depressive symptoms were associated with higher IL-6, and tricyclic antidepressant use was related to higher sCD14.

Conclusions

Our novel findings suggest that a) monocyte activation and altered coagulation may represent two pathways through which depression increases HIV-CVD risk and that b) tricyclic antidepressants may elevate and selective serotonin reuptake inhibitors may attenuate HIV-CVD risk by influencing monocyte and inflammatory activation.
Fluid-filled Cystic Lesions of the Lungs
Authors: Green Daniel B. , Wallace Andrew B. , Restrepo Carlos S. , Merrick Daniel T. , Raptis Demetrios A. , Bhalla Sanjeev , Vargas Daniel
Published: April 2020

A pulmonary cyst usually refers to an air-filled space with a smooth, thin wall. Fluid-filled cystic lesions of the lungs include a range of etiologies such as true cysts, congenital malformations, infections, and benign and malignant neoplasms. With relatively little solid component, these lesions often have similar imaging appearances to one another. This article focuses on key imaging features and clinical characteristics that can be used to narrow the differential diagnosis.
An Epidemiological Analysis and Comparison of Single Site and Multiple Site Fracture Repair: An NSQIP Analysis
Authors: Torabi Sina J. , Brauer Philip R. , Salehi Parsa P. , Ma Anthony K. , Lee Jonathan Y. , Lee Yan H.
Published: April 2020

We aimed to utilize the 2010 to 2017 National Surgical Quality Improvement Program to evaluate the epidemiology and efficacy of facial fracture repairs, specifically comparing multiple fracture site repairs (MFR) compared to single fracture site repairs (SFR). Of 4739 patients, 718 (15.2%) were found to have undergone MFR. A total of 577 (80.4%) of the MFRs involved the midface only. A total of 2114 (52.6%) of the SFRs were mid-face fractures, while 1825 (45.4%) involved the lower-face and only 82 (2.0%) involved the upper-face. The most frequent MFR was combined orbital and malar/zygoma repair (230 cases [32.0%]). When comparing MFR and SFR of the mid-face, MFR patients were more commonly male, White, operated on by plastic surgeons, presented with contaminated wounds, and active smokers. While MFRs were associated with a longer operative time (P < 0.001) and a longer postoperative hospital stay (P < 0.001), there were no differences in reoperation or readmission. Overall, complication rates were low, but slightly higher in the mid-face MFR group (1.4% in mid-face SFR and 3.0% in mid-face MFR; P = 0.019). Sub-analysis of mid-face only MFRs and middle-lower-face MFRs revealed no difference in postoperative complication rates (3.0% and 7.0%, respectively; P = 0.071). The data presented suggests that MFR are a relatively common occurrence. Although plastic surgeons perform MFRs more frequently, it is currently unclear whether the underlying reason is a product of differences in training, coding patterns, or referral patterns. Though MFRs require more hospital resources, complications rates are low. This will help manage patient expectations and guide patient counseling before surgery, as well as help to plan postoperative care.
Real-time detection of COVID-19 epicenters within the United States using a network of smart thermometers
Authors: Chamberlain S.D. , Singh I. , Ariza C. , Daitch A. , Philips P. , Dalziel B. D.
Published: April 2020

Containing outbreaks of infectious disease requires rapid identification of transmission hotspots, as the COVID-19 pandemic demonstrates. Focusing limited public health resources on transmission hotspots can contain spread, thus reducing morbidity and mortality, but rapid data on community-level disease dynamics is often unavailable. Here, we demonstrate an approach to identify anomalously elevated levels of influenza-like illness (ILI) in real-time, at the scale of US counties. Leveraging data from a geospatial network of thermometers encompassing more than one million users across the US, we identify anomalies by generating accurate, county-specific forecasts of seasonal ILI from a point prior to a potential outbreak and comparing real-time data to these expectations. Anomalies are strongly correlated with COVID-19 case counts and may provide an early-warning system to locate outbreak epicenters.

One Sentence Summary

Distributed networks of smart thermometers track COVID-19 transmission epicenters in real-time.
Dynamics of the cell fate specifications during female gametophyte development inArabidopsis
Authors: Susaki Daichi , Suzuki Takamasa , Maruyama Daisuke , Ueda Minako , Higashiyama Tetsuya , Kurihara Daisuke
Published: April 2020

The female gametophytes of angiosperms contain cells with distinct functions, such as those that enable reproduction via pollen tube attraction and fertilization. Although the female gametophyte undergoes unique developmental processes, such as several rounds of nuclear division without cell plate formation, and the final cellularization, it remains unknown when and how the cell fate is determined during their development. Here, we visualized the living dynamics of female gametophyte development and performed transcriptome analysis of its individual cell types, to assess the cell fate specifications inArabidopsis thaliana. We recorded time lapses of the nuclear dynamics and cell plate formation from the one-nucleate stage to the seven-cell stage after cellularization, using thein vitroovule culture system. The movies showed that the nuclear division occurred along the micropylar-chalazal axis. During cellularization, the polar nuclei migrated while associating with forming edge of the cell plate. Then, each polar nucleus migrated to fuse linearly towards each other. We also tracked the gene expression dynamics and identified that the expression of theMYB98pro::GFP, a synergid-specific marker, was initiated before cellularization, and then restricted to the synergid cells after cellularization. This indicated that cell fates are determined immediately after cellularization. Transcriptome analysis of the female gametophyte cells of the wild type andmyb98mutant, revealed that themyb98synergid cells had the egg cell-like gene expression profile. Although in themyb98, the egg cell-specific gene expressions were properly initiated only in the egg cells after cellularization, but subsequently expressed ectopically in one of the two synergid cells. These results, together with the various initiation timings of the egg cell-specific genes suggest the complex regulation of the individual gametophyte cells, such as cellularization-triggered fate initiation, MYB98-dependent fate maintenance, cell morphogenesis, and organelle positioning. Our system of live-cell imaging and cell-type-specific gene expression analysis provides insights into the dynamics and mechanisms of cell fate specifications in the development of female gametophytes in plants.
Structural and functional analysis of a potent sarbecovirus neutralizing antibody
Authors: Pinto Dora , Park Young-Jun , Beltramello Martina , Walls Alexandra C. , Tortorici M. Alejandra , Bianchi Siro , Jaconi Stefano , Culap Katja , Zatta Fabrizia , De Marco Anna , Peter Alessia , Guarino Barbara , Spreafico Roberto , Cameroni Elisabetta , Case James Brett , Chen Rita E. , Havenar-Daughton Colin , Snell Gyorgy , Telenti Amalio , Virgin Herbert W. , Lanzavecchia Antonio , Diamond Michael S. , Fink Katja , Veesler David , Corti Davide
Published: April 2020

SARS-CoV-2 is a newly emerged coronavirus responsible for the current COVID-19 pandemic that has resulted in more than one million infections and 73,000 deaths1,2. Vaccine and therapeutic discovery efforts are paramount to curb the pandemic spread of this zoonotic virus. The SARS-CoV-2 spike (S) glycoprotein promotes entry into host cells and is the main target of neutralizing antibodies. Here we describe multiple monoclonal antibodies targeting SARS-CoV-2 S identified from memory B cells of a SARS survivor infected in 2003. One antibody, named S309, potently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 by engaging the S receptor-binding domain. Using cryo-electron microscopy and binding assays, we show that S309 recognizes a glycan-containing epitope that is conserved within the sarbecovirus subgenus, without competing with receptor attachment. Antibody cocktails including S309 along with other antibodies identified here further enhanced SARS-CoV-2 neutralization and may limit the emergence of neutralization-escape mutants. These results pave the way for using S309 and S309-containing antibody cocktails for prophylaxis in individuals at high risk of exposure or as a post-exposure therapy to limit or treat severe disease.
Absence of SARS-CoV-2 infection in cats and dogs in close contact with a cluster of COVID-19 patients in a veterinary campus
Authors: Temmam Sarah , Barbarino Alix , Maso Djérène , Behillil Sylvie , Enouf Vincent , Huon Christèle , Jaraud Ambre , Chevallier Lucie , Backovic Marija , Pérot Philippe , Verwaerde Patrick , Tiret Laurent , van der Werf Sylvie , Eloit Marc
Published: April 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which originated in Wuhan, China, in 2019, is responsible for the COVID-19 pandemic. It is now accepted that the wild fauna, probably bats, constitute the initial reservoir of the virus, but little is known about the role pets can play in the spread of the disease in human communities, knowing the ability of SARS-CoV-2 to infect some domestic animals. We tested 21 domestic pets (9 cats and 12 dogs) living in close contact with their owners (belonging to a veterinary community of 20 students) in which two students tested positive for COVID-19 and several others (n = 11/18) consecutively showed clinical signs (fever, cough, anosmia, etc.) compatible with COVID-19 infection. Although a few pets presented many clinical signs indicative for a coronavirus infection, no animal tested positive for SARS-CoV-2 by RT-PCR and no antibodies against SARS-CoV-2 were detectable in their blood using an immunoprecipitation assay. These original data can serve a better evaluation of the host range of SARS-CoV-2 in natural environment exposure conditions.
Separable influences of reward on visual processing and choice
Authors: Soltani Alireza , Rakhshan Mohsen , Schafer Robert J , Burrows Brittany E , Moore Tirin
Published: April 2020

Primate vision is characterized by constant, sequential processing and selection of visual targets to fixate. Although expected reward is known to influence both processing and selection of visual targets, similarities and differences between these effects remains unclear mainly because they have been measured in separate tasks. Using a novel paradigm, we simultaneously measured the effects of reward outcomes and expected reward on target selection and sensitivity to visual motion in monkeys. Monkeys freely chose between two visual targets and received a juice reward with varying probability for eye movements made to either of them. Targets were stationary apertures of drifting gratings, causing the endpoints of eye movements to these targets to be systematically biased in the direction of motion. We used this motion-induced bias as a measure of sensitivity to visual motion on each trial. We then performed different analyses to explore effects of objective and subjective reward values on choice and sensitivity to visual motion in order to find similarities and differences between reward effects on these two processes. Specifically, we used different reinforcement learning models to fit choice behavior and estimate subjective reward values based on the integration of reward outcomes over multiple trials. Moreover, to compare the effects of subjective reward value on choice and sensitivity to motion directly, we considered correlations between each of these variables and integrated reward outcomes on a wide range of timescales. We found that in addition to choice, sensitivity to visual motion was also influenced by subjective reward value, even though the motion was irrelevant for receiving reward. Unlike choice, however, sensitivity to visual motion was not affected by objective measures of reward value. Moreover, choice was determined by the difference in subjective reward values of the two options whereas sensitivity to motion was influenced by the sum of values. Finally, models that best predicted visual processing and choice used sets of estimated reward values based on different types of reward integration and timescales. Together, our results demonstrate separable influences of reward on visual processing and choice, and point to the presence of multiple brain circuits for integration of reward outcomes.
Background white noise and speech facilitate visual working memory
Authors: Han Sizhu , Zhu Ruizhen , Ku Yixuan
Published: April 2020

In contrast to background white noise, the detrimental effects of background speech on verbal working memory (WM) were often explained by speech interference in the same verbal modality. Yet, those results were confounded with potential differences between arousal levels induced by speech and white noise. To address the role of arousal, in the present study, we minimized the verbal interference and used a visual WM task to test the influence of background speech or white noise. Electrodermal activity (EDA) and Electromyography (EMG) were recorded simultaneously to indicate the arousal levels of participants. Results showed that both background speech and white noise significantly improved visual WM performance. The change of performance further correlated with the change of physiological signals linked with arousal. Taken together, our results suggest that both background speech and white noise facilitate visual WM through raising the arousal level.
Application of single nuclei RNA sequencing to assess the hepatic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin
Authors: Nault Rance , Fader Kelly A. , Bhattacharya Sudin , Zacharewski Tim R.
Published: April 2020

Cell-specific transcriptional responses are lost in the averages of bulk RNA sequencing. We performed single nuclei RNA sequencing (snSeq) on frozen liver samples from male C57BL/6 mice in response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Approximately 19,907 hepatic genes were detected across 16,015 sequenced nuclei from control and treated samples. Eleven cell-(sub)types were identified including distinct hepatocyte sub-populations, consistent with the cell diversity of the liver. TCDD increased macrophages from 0.5% to 24.7%, while neutrophils were only present in treated samples. The number of differentially expressed genes correlated with the basal expression level ofAhr. In addition to expected functional enrichments within each cell-(sub)type, RAS signaling was enriched in nonparenchymal cells. snSeq also identified a Kupffer cell subtype highly expressingGpnmb, consistent with a dietary NASH model. Overall, snSeq distinguished cell-specific transcriptional changes and population shifts consistent with the hepatotoxicity of TCDD.
Selective control of working memory in prefrontal, parietal, and visual cortex
Authors: Panichello Matthew F. , Buschman Timothy J.
Published: April 2020

Cognitive control guides behavior by controlling what, where, and how information is represented in the brain. Previous work has shown parietal and prefrontal cortex direct attention, which controls the representation of external sensory stimuli1,2. However, the neural mechanisms controlling the selection of representations held ‘in mind’, in working memory, are unknown. To address this, we trained two monkeys to switch between two tasks, requiring them to either select an item from a set of items held in working memory or attend to one stimulus from a set of visual stimuli. Simultaneous neural recordings in prefrontal, parietal, and visual cortex found prefrontal cortex played a primary role in selecting an item from working memory, representing selection before parietal and visual cortex. Surprisingly, a common population representation in prefrontal cortex encoded selection of an item in working memory and attention to an external stimulus, suggesting prefrontal cortex may act as a domain-general controller. Selection acted on memory representations in two ways. First, selection improved the accuracy of memory reports by enhancing the selected item’s representation in prefrontal and parietal cortex. Second, selection transformed memory representations in a task-dependent manner. Before selection, when both items were relevant to the task, the identity of each item was represented in an independent subspace of neural activity. After selection, the representation of only the selected item was transformed into a new subspace that was used to guide the animal’s behavioral report. Together, our results provide insight into how prefrontal cortex controls working memory representations, selectively enhancing and transforming them to support behavior.
Microbial community composition is affected by press, but not pulse, seawater intrusion
Authors: Mobilian Courtney , Wisnoski Nathan I. , Lennon Jay T. , Alber Merryl , Widney Sarah , Craft Christopher B.
Published: April 2020

Tidal freshwater marshes (TFMs) are threatened by seawater intrusion, which can affect microbial communities and alter biogeochemical processes. Here, we report on Seawater Addition Long Term Experiment (SALTEx), a manipulative field experiment that investigated continuous (press) and episodic (pulse, 2 months/yr) inputs of brackish water on microbial communities in a TFM. After 2.5 years, microbial diversity was lower in press treatments than in control (untreated) plots. Sulfate reducers increased in response to both press and pulse treatments whereas methanogens did not differ among treatments. Our results suggest that microbial communities in TFMs are resilient to episodic events, but that continuous seawater intrusion may alter bacterial diversity in ways that affect ecosystem functioning.

Scientific Significance Statement

Sea level rise and seawater intrusion threaten tidal freshwater marshes (TFMs) and the important ecosystem services they provide. Intrusion of seawater in TFMs can occur across a range of timescales, such as episodic events, like storm surges or drought, or continuous intrusion as a result of rising sea level. The effects of these stressors on TFM microbial communities are not well understood. Our multi-year field manipulation of brackish water inputs revealed that microbial communities were resilient to short-term pulses of salinity whereas continuous seawater intrusion led to reduced microbial diversity along with changes in relative abundance of key functional groups. Such alterations may diminish the ability of TFMs to sequester carbon and cycle nutrients.
Graph convolutional networks for drug response prediction
Authors: Nguyen Tuan , Nguyen Giang T.T. , Nguyen Thin , Le Duc-Hau
Published: April 2020

Background

Drug response prediction is an important problem in computational personalized medicine. Many machine-learning-based methods, especially deep learning-based ones, have been proposed for this task. However, these methods often represent the drugs as strings, which are not a natural way to depict molecules. Also, interpretation (e.g., what are the mutation or copy number aberration contributing to the drug response) has not been considered thoroughly.

Methods

In this study, we propose a novel method, GraphDRP, based on graph convolutional network for the problem. In GraphDRP, drugs were represented in molecular graphs directly capturing the bonds among atoms, meanwhile cell lines were depicted as binary vectors of genomic aberrations. Representative features of drugs and cell lines were learned by convolution layers, then combined to represent for each drug-cell line pair. Finally, the response value of each drug-cell line pair was predicted by a fully-connected neural network. Four variants of graph convolutional networks were used for learning the features of drugs.

Results

We found that GraphDRP outperforms tCNNS in all performance measures for all experiments. Also, through saliency maps of the resulting GraphDRP models, we discovered the contribution of the genomic aberrations to the responses.

Conclusion

Representing drugs as graphs can improve the performance of drug response prediction.

Availability of data and materials

Data and source code can be downloaded athttps://github.com/hauldhut/GraphDRP.
Introduction of theAspergillus fumigatusα-1,2-mannosidase MsdS intoTrichoderma reeseileads to abnormal polarity and improves the ligno-cellulose degradation
Authors: Ghimire Prakriti Sharma , Ouyang Haomiao , Zhao Guangya , Xie Mingming , Zhou Hui , Yang Jinghua , Jin Cheng
Published: April 2020

α-1,2-Mannosidase is an important enzyme essential for N-glycan processing and plays a significant role in the biosynthesis and organization of fungal cell wall. Lacking of α-1,2-mannosidase leads to cell wall defect in yeast and filamentous fungi.Trichoderma reeseiis known to be non-toxic to human, and its N-glycan on secreted glycoprotein is Man8GlcNAc2. To evaluate the significance of the N-glycan processing inT. reesei, in this studyAspergillus fumigatusα-1, 2-mannosidase MsdS, an enzyme that cleaves N-linked Man8GlcNAc2in Golgi to produce Man6GlcNAc2on secreted glycoprotein, was introduced intoT. reesei. ThemsdS-expressing strain Tr-MsdS produced a major glycoform of Man6GlcNAc2on its secreted glycoproteins, instead of Man8GlcNAc2in the parent strain. Although the cell wall content ofmsdS-expressing strain Tr-MsdS was changed, it appeared that the cell wall integrity was not affected. However, phenotypes such as increased conidiation, multiple budding and random branching were observed in strain Tr-MsdS. In addition, expression of MsdS intoT. resseialso affected protein secretion and improved the ligno-cellulose degradation ofT. reesei. Our results indicate that processing of the N-glycan is species-specific and plays an important role in protein secretion inT. reesei, specially cellulases. Also, our results provide a new strategy to improve cellulases production by interfering the N-glycan processing inT. reesei.

Importance

For the first time, the N-glycan processing is shown to play an important role in polarized growth and protein secretion inT. reesei. In addition, our results show that alterated N-glycan processing enhances cellulose degradation, which provides a strategy to improve cellulases production inT. reesei.
The public health impact of fecal microbiota transplantation
Authors: Mamoon Lamia , Olesen Scott W.
Published: April 2020

Although fecal microbiota transplantation (FMT) is a recommended, clinically efficacious, and cost-effective treatment for recurrent Clostridioides difficile infection (CDI), the scale of FMT use in the United States is unknown. We developed a population-level CDI model and estimated that 48,000 FMTs could be performed annually, preventing 32,000 CDI recurrences.
Orbitofrontal-striatal structural alterations linked to negative symptoms at different stages of the schizophrenia spectrum
Authors: Kirschner Matthias , Schmidt André , Hodzic-Santor Benazir , Burrer Achim , Manoliu Andrei , Zeighami Yashar , Yau Yvonne , Abbasi Nooshin , Maatz Anke , Habermeyer Benedikt , Abivardi Aslan , Avram Mihai , Brandl Felix , Sorg Christian , Homan Philipp , Riecher-Rössler Anita , Borgwardt Stefan , Seifritz Erich , Dagher Alain , Kaiser Stefan
Published: April 2020

Among the most debilitating manifestations of schizophrenia are negative symptoms such as anhedonia and apathy. Imaging studies have linked these symptoms to morphometric abnormalities in two brain regions implicated in reward and motivation: the orbitofrontal cortex (OFC) and ventral striatum. Negative symptoms generally are associated with reduced OFC thickness, while apathy specifically maps to reduced striatal volume. However, it remains unclear whether these tissue losses are a consequence of chronic illness and its treatment, or an underlying phenotypic trait. Here we use multicentre MRI data to investigate orbitofrontal-striatal abnormalities across the schizophrenia-spectrum from healthy populations with schizotypy, to unmedicated and medicated first-episode psychosis patients, and patients with chronic schizophrenia. Striatal volumes and OFC thickness were estimated from T1-weighted images acquired in all three diagnostic groups and controls from four sites (n=337). Results were first established in one test cohort (“Zurich sample”) and replicated in three independent samples. There was a correlation between apathy and striatal volume only in healthy individuals with schizotypy; however, medicated patients exhibited larger striatal volumes, which appears to be a consequence of antipsychotic medications. The association between reduced OFC thickness and negative symptoms generally also appeared to vary along the disease course, being significant only in first-episode psychosis patients. In schizotypy there was increased OFC relative to controls. Our findings suggest that negative symptoms associate with a temporal continuum of orbitofrontal-striatal abnormalities that may predate the occurrence of schizophrenia. Thicker OFC in schizotypy may represent either compensatory or pathological mechanisms prior to disease-onset.
The role of procalcitonin in early differential diagnosis of suspected children with COVID-19
Authors: Peng Denggao , Zhang Jing , Xu Yingqi , Liu Zhichao , Wu Pengyao
Published: April 2020

Background

We aimed to identify clinical features of coronavirus disease 2019 (COVID-19) in children and evaluate the role of procalcitonin in early differential diagnosis.

Methods

A retrospective analysis was performed on all suspected pediatric cases.

Results

39 (50.6%) of 77 suspected cases were comfirmed, 4 (5.2%) of them had viral coinfection. Compared with non-COVID-19 group (n=33), COVID-19 confirmed group (n=39) had fewer fever(OR[95% CI]0.467[0.314-0.694]; P=.000) and symptoms of acute respiratory infection (0.533[0.36–0.788]; P=.001), more asymptomatic (13.568[1.895-96.729]; P=.000), and more family cluster infections (5.077[2.224-11.591]; P=.000), while computed tomography had more positive findings of viral pneumonia (1.822[1.143-2.906]; P=.008). Age (6.9[3.6-10.5] vs 5[2.1-7.6]; P=. 088) and gender were statistically insignificant. Procalcitonin (0.05[0.029-0.076] vs 0.103[0.053-0.21]; P= 000) of COVID-19 alone group (n=35) was significantly reduced. While compared with coinfection group (n=4), procalcitonin (0.05[0.029-0.076] vs 0.144[0.109-2.26]; P=.010) was also reduced. The area under curve of model is 0.834 ([95% CI][0.741-0.926]; P=.000). Procalcitonin as a differential indicator of COVID-19 alone, its area under curve is 0.809 ([0.710-0.909]; P=.000). The optimal cut-off value is 0.1 ng/mL, the sensitivity, specificity, positive and negative predictive value of differentiating are 65.9%, 78.6%, 82.9%, and 59.2%, respectively.

Conclusions

Asymptoms or mild symptoms, positive computed tomography findings and family cluster infection are the main clinical features of COVID-19 in children. With good performance, procalcitonin can provide an important basis for differentiating COVID-19 alone and other viral infection or viral coinfection.
Body stoichiometry of heterotrophs: assessing drivers of interspecific variations in elemental composition
Authors: Andrieux Benjamin , Signor Juliette , Guillou Vincent , Danger Michael , Jabot Franck
Published: April 2020

Aim

To document how body stoichiometry of heterotrophs varies globally and to assess phylogenetic, trophic, habitat and body mass drivers of this interspecific variation in elemental composition, focusing on carbon (C), nitrogen (N) and phosphorus (P).

Location

Worldwide.

Time period

1930 – 2018.

Major taxa studied

Amphibians, fishes (Euteleosteomorpha and Otomorpha), invertebrates, mammals, microbes and sauropsids (birds and reptiles).

Methods

We compiled from the scientific literature a global database of body elemental composition of heterotrophs in marine, freshwater and terrestrial realms. We used model selection and ANCOVA analyses to investigate the proportion of variance in elemental composition explained by taxonomic groups, diet, habitat and body mass. We assessed the phylogenetic signal in body stoichiometry using Blomberg’s K and Pagel’s λ statistics. We assessed the phylogenetic structure of interspecific variation in body stoichiometry using mixed models with nested taxonomic levels as random factors. We finally assessed the co-variation in elemental composition using linear models.

Results

Our database currently gathers 17848 independent observations on 1491 species. Body elemental composition was found to be widely variable among species with the four assessed drivers significantly contributing to this variation. Taxonomic group is the strongest contributor to interspecific variance for the stoichiometric traits studied, followed by habitat, diet and body mass. More precisely, stoichiometric traits are generally variable at the three taxonomic levels studied (class, order and family), resulting in a significant but relatively modest phylogenetic signal. Finally, we found significant co-variation among the three body elemental contents, resulting in taxonomic group-specific C:N:P spectrums.

Main conclusions

Our global synthesis of body stoichiometry of heterotrophs reveals a strong interspecific variability that is only modestly explained by the species attributes investigated: body mass, habitat and diet. It further reveals that this taxonomically structured residual variation in body stoichiometry seems to be constrained along taxonomic group-specific elemental spectrums.
De novo protein synthesis in distinct centrolateral amygdala interneurons is required for associative emotional memories
Authors: Shrestha Prerana , Shan Zhe , Marmarcz Maggie , Ruiz Karen San Agustin , Zerihoun Adam Taye , Juan Chien-Yu , Herrero-Vidal Pedro Manuel , Pelletier Jerry , Heintz Nathaniel , Klann Eric
Published: April 2020

To survive in a dynamic environment, animals need to identify and appropriately respond to stimuli that signal danger1,2. At the same time, animal survival also depends on suppressing the threat response during a stimulus that predicts absence of threat, i.e. safety3-5. Understanding the biological substrates of differential threat memories in which animals learn to flexibly switch between expressing and suppressing defensive responses to a threat-predictive cue and a safety cue, respectively, is critical for developing treatments for memory disorders such as PTSD6. A key brain area for processing and storing threat memories is the centrolateral amygdala (CeL), which receives convergent sensory inputs from the parabrachial nucleus and the basolateral amygdala and connects directly to the output nucleus of amygdala, the centromedial nucleus, to mediate defensive responses7-9. Despite a plethora of studies on the importance of neuronal activity in specific CeL neuronal populations during memory acquisition and retrieval10-12, little is known about regulation of their protein synthesis machinery. Consolidation of long-term, but not short-term, threat memories requires de novo protein synthesis, which suggests that the translation machinery in CeL interneurons is tightly regulated in order to stabilize associative memories. Herein, we have applied intersectional chemogenetic strategies in CeL interneurons to block cell type-specific translation initiation programs that are sensitive to depletion of eukaryotic initiation factor 4E (eIF4E) and phosphorylation of eukaryotic initiation factor 2α (p-eIF2α), respectively. We show that in a differential threat conditioning paradigm, de novo translation in somatostatin-expressing (SOM) interneurons in the CeL is necessary for long-term storage of conditioned threat response whereas de novo translation in protein kinase Cδ-expressing (PKCδ) interneurons in the CeL is essential for storing conditioned response inhibition to a safety cue. Further, we show that oxytocinergic neuromodulation of PKCδ interneurons during differential threat learning is important for long-lasting cued threat discrimination. Our results indicate that the molecular elements of a differential threat memory trace are compartmentalized in distinct CeL interneuron populations and provide new mechanistic insight into the role of de novo protein synthesis in consolidation of long-term memories.
Humans sacrifice decision-making for action execution when a demanding control of movement is required
Authors: Reynaud Amélie J. , Saleri Lunazzi Clara , Thura David
Published: April 2020

A growing body of evidence suggests that decision-making and action execution are governed by partly overlapping operating principles. Especially, previous work proposed that a shared decision urgency/movement vigor signal, possibly computed in the basal ganglia, coordinates both deliberation and movement durations in a way that maximizes the reward rate. Recent data support one aspect of this hypothesis, indicating that the urgency level at which a decision is made influences the vigor of the movement produced to express this choice. Here we investigated whether conversely, the motor context in which a movement is executed determines decision speed and accuracy. Twenty human subjects performed a probabilistic decision task in which perceptual choices were expressed by reaching movements toward targets whose size and distance from a starting position varied in distinct blocks of trials. We found strong evidence for an influence of the motor context on most of the subjects’ decision policy but contrary to the predictions of the “shared regulation” hypothesis, we observed that slow movements executed in the most demanding motor blocks in terms of accuracy were often preceded by faster and less accurate decisions compared to blocks of trials in which big targets allowed expression of choices with fast and inaccurate movements. These results suggest that decision-making and motor control are not regulated by one unique “invigoration” signal determining both decision urgency and action vigor, but more likely by independent, yet interacting, decision urgency and movement vigor signals.

NEW & NOTEWORTHY

Recent hypotheses propose that choices and movements share optimization principles derived from economy, possibly implemented by one unique context-dependent regulation signal determining both processes speed. In the present behavioral study conducted on human subjects, we demonstrate that action properties indeed influence perceptual decision-making, but that decision duration and action vigor are actually independently set depending on the difficulty of the movement executed to report a choice.