bluuebunny/crossref_metadata_2025 huggingface dataset:
How do expectant fathers respond to infant cry? Examining brain and behavioral responses and the moderating role of testosterone
Authors: Khoddam Hannah , Goldenberg Diane , Stoycos Sarah A , Horton Katelyn Taline , Marshall Narcis , Cárdenas Sofia I , Kaplan Jonas , Saxbe Darby
Published: April 2020

Expectant parents’ responses to infant cry may indicate future risk and resiliency in the parent-child relationship. Most studies of parental reactivity to infant cry have focused on mothers, and few studies have focused on expectant fathers, although fathers make important contributions to parenting. Additionally, although different responses to infant cry (behavioral, psychological and neural) are hypothesized to track together, few studies have analyzed them concurrently. The current investigation aimed to address these gaps by characterizing multimodal responses to infant cry within expectant fathers and testing whether prenatal testosterone moderates these responses. Expectant fathers responded to infant cry vs frequency-matched white noise with increased activation in bilateral areas of the temporal lobe involved in processing speech sounds and social and emotional stimuli. Handgrip force, which has been used to measure parents’ reactivity to cry sounds in previous studies, did not differentiate cry from white noise within this sample. Expectant fathers with higher prenatal testosterone showed greater activation in the supramarginal gyrus, left occipital lobe and precuneus cortex to cry sounds. Expectant fathers appear to interpret and process infant cry as a meaningful speech sound and social cue, and testosterone may play a role in expectant fathers’ response to infant cry.
The Gray Area of Defining Sexual Assault: An Exploratory Study of College Students’ Perceptions
Authors: Baldwin-White Adrienne , Bazemore Brooke
Published: April 2020

College-age women are disproportionately at risk of experiencing sexual assault. Sexual assault causes tremendous psychological distress for survivors. Therefore, it is imperative to understand the perceptions that affect the perpetration of sexual assault. One of those potential factors is how college students conceptualize and define sexual assault. The current qualitative study demonstrated that college students do not have consistent images of sexual assault and often rely on their own perceptions and experiences to define it. Creating and providing a standard of sexual assault based on the reality of college students can provide a foundation for creating effective prevention strategies.
A Grain Rot of Rice in Iran Caused by a Xanthomonas Strain Closely Related to X. sacchari
Authors: Mirghasempour S. Ali , Huang Shiwen , Studholme David J. , Brady Carrie L.
Published: April 2020

Rice grain rot disease was detected for the first time in Mazandaran Province, Iran. The bacteria isolated from infected rice plants showed grains rotted and darkening. A Xanthomonas strain closely connected to X. sacchari was identified using molecular and whole genome sequencing approaches confirmed as the causal agent by fulfilling Koch’s postulates.
Pediatric hypertension
Authors: Benenson Irina , Waldron Frederick A. , Porter Sallie
Published: April 2020

The prevalence of pediatric hypertension is growing. Hypertension during childhood remains a major risk factor for adverse cardiovascular events later in life. NPs should be aware of current guidelines on screening, diagnosis, and treatment of hypertension in children to improve care for this patient population.
Sugammadex versus Neostigmine for Reversal of Neuromuscular Blockade and Postoperative Pulmonary Complications (STRONGER)
Authors: Kheterpal Sachin , Vaughn Michelle T. , Dubovoy Timur Z. , Shah Nirav J. , Bash Lori D. , Colquhoun Douglas A. , Shanks Amy M. , Mathis Michael R. , Soto Roy G. , Bardia Amit , Bartels Karsten , McCormick Patrick J. , Schonberger Robert B. , Saager Leif
Published: April 2020

Background

Five percent of adult patients undergoing noncardiac inpatient surgery experience a major pulmonary complication. The authors hypothesized that the choice of neuromuscular blockade reversal (neostigmine vs. sugammadex) may be associated with a lower incidence of major pulmonary complications.

Methods

Twelve U.S. Multicenter Perioperative Outcomes Group hospitals were included in a multicenter observational matched-cohort study of surgical cases between January 2014 and August 2018. Adult patients undergoing elective inpatient noncardiac surgical procedures with general anesthesia and endotracheal intubation receiving a nondepolarizing neuromuscular blockade agent and reversal were included. Exact matching criteria included institution, sex, age, comorbidities, obesity, surgical procedure type, and neuromuscular blockade agent (rocuronium vs. vecuronium). Other preoperative and intraoperative factors were compared and adjusted in the case of residual imbalance. The composite primary outcome was major postoperative pulmonary complications, defined as pneumonia, respiratory failure, or other pulmonary complications (including pneumonitis; pulmonary congestion; iatrogenic pulmonary embolism, infarction, or pneumothorax). Secondary outcomes focused on the components of pneumonia and respiratory failure.

Results

Of 30,026 patients receiving sugammadex, 22,856 were matched to 22,856 patients receiving neostigmine. Out of 45,712 patients studied, 1,892 (4.1%) were diagnosed with the composite primary outcome (3.5% sugammadex vs. 4.8% neostigmine). A total of 796 (1.7%) patients had pneumonia (1.3% vs. 2.2%), and 582 (1.3%) respiratory failure (0.8% vs. 1.7%). In multivariable analysis, sugammadex administration was associated with a 30% reduced risk of pulmonary complications (adjusted odds ratio, 0.70; 95% CI, 0.63 to 0.77), 47% reduced risk of pneumonia (adjusted odds ratio, 0.53; 95% CI, 0.44 to 0.62), and 55% reduced risk of respiratory failure (adjusted odds ratio, 0.45; 95% CI, 0.37 to 0.56), compared to neostigmine.

Conclusions

Among a generalizable cohort of adult patients undergoing inpatient surgery at U.S. hospitals, the use of sugammadex was associated with a clinically and statistically significant lower incidence of major pulmonary complications.

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Collapse of Global Neuronal States in Caenorhabditis elegans under Isoflurane Anesthesia
Authors: Awal Mehraj R. , Wirak Gregory S. , Gabel Christopher V. , Connor Christopher W.
Published: April 2020

Background

A comprehensive understanding of how anesthetics facilitate a reversible collapse of system-wide neuronal function requires measurement of neuronal activity with single-cell resolution. Multineuron recording was performed in Caenorhabditis elegans to measure neuronal activity at varying depths of anesthesia. The authors hypothesized that anesthesia is characterized by dyssynchrony between neurons resulting in a collapse of organized system states.

Methods

Using light-sheet microscopy and transgenic expression of the calcium-sensitive fluorophore GCaMP6s, a majority of neurons (n = 120) in the C. elegans head were simultaneously imaged in vivo and neuronal activity was measured. Neural activity and system-wide dynamics were compared in 10 animals, progressively dosed at 0%, 4%, and 8% isoflurane. System-wide neuronal activity was analyzed using principal component analysis.

Results

Unanesthetized animals display distinct global neuronal states that are reflected in a high degree of correlation (R = 0.196 ± 0.070) between neurons and low-frequency, large-amplitude neuronal dynamics. At 4% isoflurane, the average correlation between neurons is significantly diminished (R = 0.026 ± 0.010; P < 0.0001 vs. unanesthetized) and neuron dynamics shift toward higher frequencies but with smaller dynamic range. At 8% isoflurane, interneuronal correlations indicate that neuronal activity remains uncoordinated (R = 0.053 ± 0.029; P < 0.0001 vs. unanesthetized) with high-frequency dynamics that are even further restricted. Principal component analysis of unanesthetized neuronal activity reveals distinct structure corresponding to known behavioral states. At 4% and 8% isoflurane this structure is lost and replaced with randomized dynamics, as quantified by the percentage of total ensemble variance captured by the first three principal components. In unanesthetized worms, this captured variance is high (88.9 ± 5.4%), reflecting a highly organized system, falling significantly at 4% and 8% isoflurane (57.9 ± 11.2%, P < 0.0001 vs. unanesthetized, and 76.0 ± 7.9%, P < 0.001 vs. unanesthetized, respectively) and corresponding to increased randomization and collapse of system-wide organization.

Conclusions

Anesthesia with isoflurane in C. elegans corresponds to high-frequency randomization of individual neuron activity, loss of coordination between neurons, and a collapse of system-wide functional organization.

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Proliferating Onychomatricoma. Clinical, Dermoscopical, and Pathologic Features of Onychomatricoma New Variant Resembling Onycholemmal/Squamous Cell Carcinoma
Authors: Perrin Christophe , Ambrosetti Damien , Balme Brigitte , Thomas Luc
Published: April 2020

Proliferating onychomatricoma is a new challenging variant of onychomatricoma that can clinically and histologically mimic squamous cell carcinoma/onycholemmal carcinoma. This is a retrospective case series study of the clinicopathologic and dermoscopic features of 6 patients with a pathologic diagnosis of proliferating onychomatricoma, which was conducted in the dermatology and dermatopathology departments of 2 university hospitals and a private nail's dermatology consultation. The clinical, histological, and immunohistochemical features and follow-up of 6 patients with proliferating onychomatricoma were analyzed; we compare our finding with 6 cases of conventional onychomatricoma. The female-to-male ratio was 1:1 with involvement of fingers in 4 and toe in 2. Among the symptoms were verrucous lesion simulating squamous cell carcinoma, nail thickening, periungual erythema, and pain; symptom duration ranged from 5 to 8 years. Clinical, dermoscopical en face free-margin view, and nail-clipping histologic findings reveal a nail wall-like pattern with pitting. Intraoperative, noncontact, polarizing, light dermoscopy was available in 1 case and showed the typical signs of onychomatricoma (OM). Histologically, all cases showed a well-differentiated, infiltrative, squamous, proliferative lesion exhibiting a lobulated and cystic pattern of growth in the dermis. Abrupt keratinization reminiscent of trichilemmal keratinization, but corresponding in fact to keratogenous spheres, was noted as well as a dysmaturative epithelial pattern. No atypical cytomorphological changes were found. Proliferating onychomatricoma is a new variant of onychomatricoma, which can be misdiagnosed as squamous cell carcinoma/onycholemmal carcinoma; its proper recognition may minimize morbidity associated with inappropriate treatment. Proliferating OM can be differentiated from conventional OM clinically by a free-edge wall-like pattern and on histology of nail clipping by the relatively small size of the cavities. Dermoscopic and nail clipping attributes as free-edge honeycomb-like cavities associated with conventional OM are well established and permit a diagnosis of OM without an invasive nail biopsy. The free-edge wall-like pattern is a distinct new dermoscopic and nail-clipping pattern that should raise for the others onychogenic neoplasms and prompt the clinician to obtain a biopsy specimen. In addition to proliferating OM, the differential diagnosis includes a micropapilliferum variant of OM, onychocytic matricoma, and onychocytic carcinoma.
Multilevel analysis exploring the relative importance of workplace resources in explaining nurses’ workload perceptions: Are we setting the right focus?
Authors: Oppel Eva-Maria , Mohr David C.
Published: April 2020

Background

Nurses’ workload has become increasingly recognized as an important determinant of nurse turnover and shortage and has been also associated with poorer quality of care. Despite strong evidence that heavy workloads have negative consequences, we still lack a comprehensive understanding of the workplace characteristics that contribute most to improving nurses’ workload, the relative importance of each in doing so, or indeed the workplace characteristics and other factors that drive nurses’ perceptions of their workload.

Purpose

The aim of this study was to examine workplace resources as antecedents of nurses’ perceptions of their workload and to investigate their relative importance in explaining workload perceptions. We considered workplace resources related to staffing, professional relationships, and technology.

Methodology

The study sample comprised nurse-reported and administrative data from U.S. Veterans Health Administration hospitals between 2014 and 2017. Our multilevel analyses are based on data from 20,330 nurses working in 273 work groups at 123 hospitals. We developed and empirically tested a theoretical model using multilevel mixed-effects linear regression. The relative importance of workplace resources was assessed by dominance analysis.

Results

Staffing levels, relational climate, and information technology were significantly associated with nurses’ workload perceptions. Dominance analysis indicated that relational resources are the most important measure in explaining nurses’ workload perceptions.

Practice Implications

This is the first study to examine the relative importance of workplace resources in explaining nurses’ perceptions of their workload. Our results suggest that much might be gained by investing in interventions to boost relational resources. In turn, these findings could lead to more targeted, effective, and resource efficient interventions to improve nurses’ workload.
REVISED CLASSIFICATION OF THE OPTICAL COHERENCE TOMOGRAPHY OUTER RETINAL BANDS BASED ON CENTRAL SEROUS CHORIORETINOPATHY ANALYSIS
Authors: Bloom Steven M. , Singal Inder P.
Published: April 2020

Purpose:

To evaluate the optical coherence tomography (OCT) imaging findings in recent onset neurosensory retinal detachments induced by central serous chorioretinopathy and to attempt to corroborate these findings with proposed anatomical correlates.

Methods:

Retinal detachments due to central serous chorioretinopathy of less than 3 months' duration and the surrounding area were scanned with OCT. The imaging of the outer retinal bands was evaluated according to proposals by Cuenca et al and the IN•OCT Consensus classification.

Results:

Optical coherence tomography findings in 11 eyes (11 patients) with CSC showed that all hyperreflective bands above Band 4 were variably continuous within the outer portion of the serous detachment. We then attempted to reconcile inconsistencies in current explanations for the outer retinal bands to propose changes to the outer retinal OCT nomenclature.

Conclusion:

Our patients' OCT findings support the current standard that Band 3 is an outer retinal structure and that Band 4 represents the retinal pigment epithelium/Bruch complex. Confusion exists regarding whether the interdigitation zone extends halfway up or for the full length of the outer segments, and the hyporeflective band between Bands 3 and 4 has yet to receive an appropriate term. We therefore propose a modification to the IN•OCT Consensus classification by renaming the trilaminar hyporeflective, hyperreflective, and hyporeflective bands between Bands 2 and 4 as the outer segment–interdigitation zone complex consisting of the inner, middle, and outer segment–interdigitation zone, respectively.
ANATOMICAL CHANGES ON SEQUENTIAL MULTIMODAL IMAGING IN PERIFOVEAL EXUDATIVE VASCULAR ANOMALOUS COMPLEX
Authors: Verhoekx Jennifer S. N. , Smid Lisette M. , Vermeer Koenraad A. , Martinez Ciriano José P. , Yzer Suzanne
Published: April 2020

Purpose:

To report a series of 21 patients with perifoveal exudative vascular anomalous complex (PEVAC) and to investigate the anatomical changes over time.

Methods:

We conducted a retrospective study. Clinical data of consecutive patients, presenting at the Rotterdam Eye Hospital between 2014 and 2019, were analyzed. The data collected included best-corrected visual acuity, fundus photography, optical coherence tomography (OCT), OCT-angiography, fluorescence angiography, and indocyanine green angiography.

Results:

We included 21 patients with a PEVAC lesion with a mean follow-up of 24.3 ± 13.8 months (range, 9–46 months). Patients with PEVAC were on average 75.3 ± 11.1 years (range, 53–90 years). The large perifoveal vascular aneurysmal abnormality was associated with small retinal hemorrhages in six patients and hard exudates in three patients. The PEVAC lesion was associated with intraretinal cystic spaces on OCT in 15 patients. Twelve of 21 patients showed no changes in cystic spaces on OCT during follow-up: 9 patients had stable cystic spaces and 3 patients had no cystic spaces. In contrast, in 9 of 21 patients, we observed changes in cystic spaces on OCT during follow-up. In two patients, cystic spaces appeared during follow-up, and in seven patients, there was a spontaneous resolution of cystic spaces. In three of these seven patients, the PEVAC lesion completely disappeared. Two patients, with stable intraretinal cystic spaces on OCT, were treated with intravitreal injections of anti–vascular endothelial growth factor without improvement.

Conclusion:

Perifoveal exudative vascular anomalous complex is an idiopathic perifoveal retinal vascular abnormality that is associated with intraretinal cystic spaces. These intraretinal cystic spaces associated with a PEVAC lesion, and even the PEVAC lesion itself, can have a spontaneous resolution over time.
A new noninvasive method for assessing mild coronary atherosclerosis: transthoracic convergent color Doppler after heart rate reduction. Validation vs. intracoronary ultrasound
Authors: Caiati Carlo , Lepera Mario Erminio , Pollice Paolo , Iacovelli Fortunato , Favale Stefano
Published: April 2020

Background

A more sensitive transthoracic color Doppler technology (convergent color Doppler), along with a heart rate (HR) reduction and new tomographic planes, can greatly improve coronary blood flow velocity (BFV) recordings in the left main (LMCA) and left anterior descending (LAD) coronary arteries, allowing the detection of even a slight acceleration of BFV due to mild coronary stenosis.

Methods

A group of 26 patients underwent convergent color Doppler transthoracic echocardiography (CC-Doppler TTE) in the LMCA and in the LAD coronary arteries before and after HR lowering. A second group of 71 patients scheduled for intravascular ultrasound, expanded to 96 with 25 more patients with normal LAD (by angiography/low likelihood of disease), underwent BFV Doppler recordings by CC-Doppler TTE of the whole LAD (specifically the proximal, mid and distal segments) to detect a localized increase in BFV, after attaining maximal and reference BFV in each segment.

Results

In the first group, HR reduction dramatically improved the detection of optimal flow in the LMCA and LAD, from 4 to 54% and from 6 to 94% of the segments, respectively (P < 0.001). In the second group intravascular ultrasonography (IVUS) showed mild stenoses in 60 patients. The maximum velocity was higher in the diseased segment than normal segments (49 ± 24 vs. 33 ± 11 cm/s; P < 0.001) and as the reference velocity was similar (32 ± 9 vs. 33 ± 11 cm/s; P = ns), the % increase was also higher (52 ± 52 vs. 0.7 ± 3%; P < 0.001). Using a >21% increase in velocity as a cutoff value, the sensitivity and specificity of CC-Doppler TTE in detecting at least one LAD plaque were 87% (52/60 patients [pts]) and 100% (36/36 pts), respectively.

Conclusion

CC-Doppler TTE evaluation of LAD BFV is greatly improved after reducing HR, allowing accurate noninvasive assessment of mild LAD stenosis with no radiation exposure.
The relationship between fibrinogen-to-albumin ratio and in-stent restenosis in patients with coronary artery disease undergoing drug-eluting stenting
Authors: Chen Tao , Sun Jing-Lin , Zhang Jian
Published: April 2020

Background

In-stent restenosis (ISR) remains a significant clinical problem in patients with coronary artery disease (CAD) treated with percutaneous coronary intervention (PCI). Recent studies identified the fibrinogen-to-albumin ratio (FAR) as a novel inflammatory marker to predict inflammation in chronic diseases. This study aimed to investigate the relationship between FAR and ISR in patients with DES implantation.

Methods

A total of 506 consecutive CAD patients were enrolled. Subjects history of successful native vessel PCI with DES at least 12 months prior to undergoing repeat angiography for chest pain. Patients were divided between ISR group (n = 125) and no-ISR group (n = 381). ISR was defined as luminal stenosis ≥50% located within the stent or up to 5 mm beyond the stent edges by the quantitative coronary analysis. Laboratory parameters were measured before angiography. Significant factors associated with ISR were evaluated by multivariate logistic regression analysis.

Results

Baseline characteristics were similar between the ISR and no-ISR groups. The ISR group had significantly higher FAR level compared with the no-ISR group (73.26 ± 17.68 vs. 64.90 ± 15.88, P < 0.05). Furthermore, the ISR group had significantly lower albumin level and higher prevalence of diabetes mellitus compared to no-ISR (P < 0.05). In a multivariate analysis, FAR (odds ratio [OR] = 1.039, 95% confidence interval (CI) = 1.024–1.054), albumin (OR = 0.923, 95% CI = 0.389–0.977) and diabetes mellitus (OR = 2.663, 95% CI = 1.587–4.468) were significantly associated with ISR.

Conclusion

FAR is significantly associated with the development of ISR in CAD patients undergoing PCI with DES implantation.
Primary Cutaneous CD4+ Small/Medium T-Cell Lymphoproliferative Disorders
Authors: Beltzung Fanny , Ortonne Nicolas , Pelletier Laura , Beylot-Barry Marie , Ingen-Housz-Oro Saskia , Franck Frédéric , Pereira Bruno , Godfraind Catherine , Delfau Marie-Hélène , D’Incan Michel , Vergier Béatrice
Published: April 2020

Primary cutaneous CD4+small/medium T-cell lymphoproliferative disorder (PCSMLPD) is a recently recognized entity in the 2017 World Health Organization (WHO) classification. It belongs to the T-follicular helper (TFH) lymphoproliferations. The clinical, pathologic, and molecular features of this localized disease are underresearched. We conducted a retrospective multicentric study of 60 patients with a PCSMLPD that presented as a single cutaneous lesion. Clinical, pathologic, and targeted molecular analyses were performed. PCSMLPD presented mostly as a nodule (45%), located on the head and neck area (50%) in adults (mean age: 59 y [43.3 to 75.2]). All patients had an indolent disease course, either at initial staging or during follow-up (mean: 16.6 mo [1.3 to 31.9]). Spontaneous regression was reported in 31.9% of cases. The infiltrates were most often nodular and/or diffuse, expanding in the whole dermis (78%, Pattern 1), rather than subepidermal band-like in the superficial dermis (22%, Pattern 2). Epidermotropism, folliculotropism, and capillary hyperplasia were common. The expression of TFH lineage markers was more extensive in lesions with Pattern 2, but a substantial B-cell infiltrate was seen in both types of lesions. A clonal rearrangement of the TCR genes was identified in 68% of cases. One sample of the 13 tested revealed a mutation in theDNMT3Agene among the 9 genes studied (TET2,DNMT3A,IDH2,RHOA,SETD2,PLCG1,STAT3, STAT5B, andCD28). PCSMLPD follows a benign clinical course and can spontaneously regress after biopsy. Although PCSMLPD expresses TFH lineage markers, mutations usually found in angioimmunoblastic T-cell lymphomas are uncommon.
Pregnancy-associated Inflammatory Myofibroblastic Tumors of the Uterus Are Clinically Distinct and Highly Enriched for TIMP3-ALK and THBS1-ALK Fusions
Authors: Devereaux Kelly A. , Fitzpatrick Megan B. , Hartinger Sara , Jones Carol , Kunder Christian A. , Longacre Teri A.
Published: April 2020

As inflammatory myofibroblastic tumors (IMTs) have become more widely recognized in the female genital tract, an intriguing subset of uterine tumors associated with pregnancy has emerged. Whether uterine IMTs occurring in the setting of pregnancy are clinically or biologically distinct from other uterine IMTs is unknown. Furthermore, little is known about the perinatal factors that may influence the development of these tumors. Here, we report the largest case series of 8 pregnancy-associated IMTs. All pregnancy-associated IMTs in this series occurred in association with pregnancy complications, including abnormal implantation (n=1), gestational diabetes (n=2), preeclampsia and/or HELLP syndrome (n=2), antiphospholipid syndrome (n=1), premature rupture of membranes (n=1), and hepatitis B (n=1). Notably, all IMTs were expelled at the time of delivery or immediately postpartum and were either adherent to the placenta or presented as separate, detached tissue. Tumors ranged from 2.0 to 6.0 cm (median, 3.9 cm), were well-circumscribed and showed classic histologic features of IMTs, including myxoid stroma and a lymphoplasmacytic infiltrate. Seven of 8 cases were positive by ALK immunohistochemistry and confirmed to have an ALK gene rearrangement by fluorescent in situ hybridization and RNA sequencing. The ALK-rearranged IMTs were found to be particularly enriched for TIMP3-ALK (n=5) and THBS1-ALK (n=2) fusions. The single case that was negative for an ALK rearrangement exhibited the classic morphology of an IMT. None of the 4 cases with available clinical follow-up recurred. The clinicopathologic features of pregnancy-associated IMTs in this series in conjunction with those reported in the literature suggests that these may be transient tumors that develop during pregnancy and shed at parturition; they appear to have a relatively indolent clinical course and favorable outcome, although studies with a longer duration of follow-up are still required.
Immunotherapy and Response Assessment in Malignant Glioma
Authors: Bagley Stephen J. , Desai Arati S. , Nasrallah MacLean P. , O’Rourke Donald M.
Published: April 2020

Glioblastoma (GBM) is the deadliest form of brain cancer and recurs uniformly. Despite aggressive treatment with maximal safe surgical resection, adjuvant radiation with temozolomide chemotherapy, and alternating electrical field therapy, median survival for newly diagnosed GBM remains <2 years. Novel therapies are desperately needed. Immunotherapy, which has led to significant improvement in patient outcomes across many tumor types, is currently being studied in a large number of GBM clinical trials. One of the biggest challenges in immunotherapy trials in GBM has been accurate response assessment using currently available imaging modalities, including magnetic resonance imaging. In this review, we will discuss the rationale for immunotherapy for GBM, immunotherapeutic modalities currently under clinical evaluation in GBM, and the challenges and recent advances in imaging response assessment in GBM immunotherapy.
Machine Learning and Deep Neural Network Applications in the Thorax
Authors: Remy-Jardin Martine , Faivre Jean-Baptiste , Kaergel Rainer , Hutt Antoine , Felloni Paul , Khung Suonita , Lejeune Anne-Laure , Giordano Jessica , Remy Jacques
Published: April 2020

The radiologic community is rapidly integrating a revolution that has not fully entered daily practice. It necessitates a close collaboration between computer scientists and radiologists to move from concepts to practical applications. This article reviews the current littérature on machine learning and deep neural network applications in the field of pulmonary embolism, chronic thromboembolic pulmonary hypertension, aorta, and chronic obstructive pulmonary disease.
The neonicotinoid insecticide imidacloprid disrupts bumblebee foraging rhythms and sleep
Authors: Tasman Kiah , Rands Sean A. , Hodge James J.L.
Published: April 2020

Neonicotinoids have been implicated in the large declines observed in flying insects such as bumblebees, an important group of pollinators[1]. Neonicotinoids are agonists of nicotinic acetylcholine receptors that are found throughout the insect central nervous system, and are the main mediators of synaptic neurotransmission[2]. These receptors are important for the function of the insect central clock and circadian rhythms[3, 4]. The clock allows pollinators to coincide their activity with the availability of floral resources, favourable flight temperatures, as well as impacting learning, navigation and communication[5]. Here we show that exposure to the field relevant concentration of 10 µg/L of imidacloprid can cause a reduction in foraging activity and reduce both locomotor and foraging rhythmicity inBombus terrestris. Foragers showed an increase in daytime sleep and an increase in the proportion of activity occurring at night. This would likely negatively impact foraging and pollination opportunities, reducing the ability of the colony to grow and reproduce, endangering crop yields.
An emerging target paradigm evokes fast visuomotor responses on human upper limb muscles
Authors: Kozak Rebecca A. , Cecala Aaron L. , Corneil Brian D.
Published: April 2020

To reach towards a seen object, visual information has to be transformed into motor commands. Visual information such as the object’s colour, shape, and size is processed and integrated within numerous brain areas, then ultimately relayed to the motor periphery. In some instances we must react as fast as possible. These fast visuomotor transformations, and their underlying neurological substrates, are poorly understood in humans as they have lacked a reliable biomarker. Stimulus-locked responses (SLRs) are short latency (<100 ms) bursts of electromyographic (EMG) activity representing the first wave of muscle recruitment influenced by visual stimulus presentation. SLRs provide a quantifiable output of rapid visuomotor transformations, but SLRs have not been consistently observed in all subjects in past studies. Here we describe a new, behavioural paradigm featuring the sudden emergence of a moving target below an obstacle that consistently evokes robust SLRs. Human participants generated visually-guided reaches toward or away from the emerging target using a robotic manipulandum while surface electrodes recorded EMG activity from the pectoralis major muscle. In comparison to previous studies that investigated SLRs using static stimuli, the SLRs evoked with this emerging target paradigm were larger, evolved earlier, and were present in all participants. Reach reaction times (RTs) were also expedited in the emerging target paradigm. This paradigm affords numerous opportunities for modification that could permit systematic study of the impact of various sensory, cognitive, and motor manipulations on fast visuomotor responses. Overall, our results demonstrate that an emerging target paradigm is capable of consistently and robustly evoking activity within a fast visuomotor system.

We present a new behavioual paradigm that elicits robust fast visuomotor responses on human upper limb muscles during visually guided reaches.
Recurrent processing drives experience-dependent plasticity for perceptual decisions
Authors: Jia Ke , Zamboni Elisa , Kemper Valentin , Rua Catarina , Reis Goncalves Nuno , Ng Adrian Ka Tsun , Rodgers Christopher T. , Williams Guy , Goebel Rainer , Kourtzi Zoe
Published: April 2020

Learning and experience are critical for translating ambiguous sensory information from our environments to perceptual decisions. Yet, evidence on how training molds the adult human brain remains controversial, as fMRI at standard resolution does not allow us to discern the finer-scale mechanisms that underlie sensory plasticity. Here, we combine ultra-high field (7T) functional imaging at sub-millimetre resolution with orientation discrimination training to interrogate experience-dependent plasticity across cortical depths. Our results provide evidence for recurrent plasticity, by contrast to sensory encoding vs. feedback mechanisms. We demonstrate that learning alters orientation-specific representations in superficial rather than middle V1 layers, suggesting changes in read-out rather than input signals. Further, learning increases feedforward rather than feedback layer-to-layer connectivity in occipito-parietal regions, suggesting that sensory plasticity gates perceptual decisions. Our findings propose finer-scale plasticity mechanisms that re-weight sensory signals to inform improved decisions, bridging the gap between micro- and macro-circuits of experience-dependent plasticity.
Lipid Landscape of the Human Retina and Supporting Tissues Revealed by High Resolution Imaging Mass Spectrometry
Authors: Anderson David M.G. , Messinger Jeffrey D. , Patterson Nathan H. , Rivera Emilio S. , Kotnala Ankita , Spraggins Jeffrey M. , Caprioli Richard M. , Curcio Christine A. , Schey Kevin L.
Published: April 2020

The human retina evolved to facilitate complex visual tasks. It supports vision at light levels ranging from starlight to sunlight, and its supporting tissues and vasculature regulate plasma-delivered lipophilic essentials for vision, including retinoids (vitamin A derivatives). The human retina is of particular interest because of its unique anatomic specializations for high-acuity and color vision that are also vulnerable to prevalent blinding diseases. The retina’s exquisite cellular architecture is composed of numerous cell types that are aligned horizontally, giving rise to structurally distinct cell, synaptic, and vascular layers that are visible in histology and in diagnostic clinical imaging. Suitable for retinal investigations, MALDI imaging mass spectrometry (IMS) technologies are now capable of providing images at low micrometer spatial resolution with high levels of chemical specificity. In this study, a multimodal imaging approach combined with a recently developed method of high accuracy multi-image registration was used to define the localization of lipids in human retina tissue at laminar, cellular, and sub-cellular levels. Data acquired by IMS combined with autofluorescence and bright-field microscopy of human retina sections in macular and peripheral regions indicate differences in distributions and abundances of lipid species across and within single cell types. Of note is localization of signals within specific layers of macula, localization within different compartments of photoreceptors and RPE, complementarity of signals between macular retina and non-macular RPE, and evidence that lipids differing by a single double bond can have markedly different distributions.
Spatial cueing effects are not what we thought: on the timing of attentional deployment
Authors: Yaron Itay , Lamy Dominique
Published: April 2020

Extensive research has shown that objects that are salient or match our task goals are most likely to capture attention. But are we at the mercy of the constant changes occurring in our environment, and automatically move our attention to the ever-changing location with the highest priority? Or do we wait for clues that the appropriate moment has arrived to deploy our attention? We addressed this hitherto neglected issue in three experiments. Using a spatial-cueing paradigm, we examined whether attention is deployed as soon as a salient change occurs (the cue), or only when the context signaling that attention should be deployed appears (the search display). The cue matched the target color and was therefore expected to enjoy high attentional priority. We used two separate response compatibility manipulations, one pertaining to the cue, in the cueing display, and the other to the cued distractor, in the search display. Neutral conditions allowed us to disentangle the respective effects of these manipulations. Our results support the hypothesis that attention does not occur until the search-relevant context appears. These findings challenge the traditional interpretation of spatial-cueing effects. They are discussed within the Priority Accumulation Framework (PAF) that we confront to other attention models.
Defining the resilience of the human salivary microbiota by a 520 days longitudinal study in confined environment: the Mars500 mission
Authors: Bacci Giovanni , Mengoni Alessio , Emiliani Giovanni , Chiellini Carolina , Cipriani Edoardo Giovanni , Bianconi Giovanna , Canganella Francesco , Fani Renato
Published: April 2020

The human microbiota plays several roles in health and disease but is often difficult to determine which part is in intimate relationships with the host vs. the occasional presence. During the Mars500 mission, six crewmembers lived completely isolated from the outer world for 520 days following standardized diet regimes. The mission constitutes the first spaceflight simulation to Mars and was a unique experiment to determine, in a longitudinal study design, the composition and importance of the resident vs. a more variable microbiota—the fraction of the human microbiota that changes in time and according to environmental conditions—in humans. Here we report the characterization of the salivary microbiota from 88 samples taken during and after the mission for a total of 720 days. Amplicon sequencing of the V3-V4 region of 16S rRNA gene was performed and results were analyzed monitoring the diversity of the microbiota while evaluating the effect of the three main variables present in the experimental system: time, diet, and individuality of each subject. Results, though showing statistically significant effects of all three variables, highlighted a main contribution of salivary microbiota personalized features, that is an individual-based resilience of the microbiota. Such findings open the way to consider salivary microbiota under the light of a pronounced personalization even after sharing the same physical space for more than a year.
The Alzheimer’s disease-associated protectivePlcγ2-P522R variant promotes beneficial microglial functions
Authors: Takalo Mari , Wittrahm Rebekka , Wefers Benedikt , Parhizkar Samira , Jokivarsi Kimmo , Kuulasmaa Teemu , Mäkinen Petra , Martiskainen Henna , Wurst Wolfgang , Xiang Xianyuan , Marttinen Mikael , Poutiainen Pekka , Haapasalo Annakaisa , Hiltunen Mikko , Haass Christian
Published: April 2020

Background

Microglia-specific genetic variants are enriched in several neurodegenerative diseases, including Alzheimer’s disease (AD), implicating a central role for alterations of the innate immune system in the disease etiology. A rare coding variant in thePLCG2gene (rs72824905, p.P522R) selectively expressed in microglia and macrophages was recently identified and shown to reduce the risk for AD.

Methods

To assess the role of this variant in the context of immune cell functions, we generated a Plcγ2-P522R knock-in (KI) mouse model using CRISPR/Cas9 gene editing.

Results

Functional analyses of macrophages derived from homozygous KI mice and wild type (WT) littermates revealed that the P522R variant potentiates the primary function of Plcγ2 as a Pip2-metabolizing enzyme. This was associated with improved survival, enhanced phagocytic activity, and increased acute inflammatory response of the KI cells. Enhanced phagocytosis was also observed in mouse BV2 microglia-like cells overexpressing human PLCγ2-P522R, but not in PLCγ2-WT expressing cells. Furthermore, the brain mRNA signature together with microglia-specific PET imaging indicated microglia activation in Plcγ2-P522R KI mice.

Conclusion

Thus, we have delineated cellular mechanisms of the protective Plcγ2-P522R variant, which provide further support for the emerging idea that activated microglia exert protective functions in AD.
Prenatal treatment with rapamycin restores enhanced hippocampal mGluR-LTD and mushroom spine size in a Down’s syndrome mouse model
Authors: Urbano-Gámez Jesús David , Benito Itziar , Casañas Juan José , Montesinos María Luz
Published: April 2020

Down syndrome (DS) is the most frequent genetic cause of intellectual disability including hippocampal-dependent memory deficits. We have previously reported hippocampal mTOR (mammalian target of rapamycin) hyperactivation, and related plasticity as well as memory deficits in Ts1Cje mice, a DS experimental model. Here we report that performance of Ts1Cje mice in novel object recognition (NOR) is impaired, but it is ameliorated by rapamycin treatment. Proteome characterization of hippocampal synaptoneurosomes (SNs) from these mice predicted an alteration of synaptic plasticity pathways, including long term depression (LTD), which was reversed by rapamycin. Accordingly, mGluR-LTD (metabotropic Glutamate Receptor-Long Term Depression) is enhanced in the hippocampus of Ts1Cje mice and this is correlated with an increased proportion of a particular category of mushroom spines in hippocampal pyramidal neurons. Remarkably, prenatal treatment of these mice with rapamycin normalized both phenotypes, supporting the therapeutic potential of rapamycin/rapalogs for DS intellectual disability.
Driving Integrative Structural Modeling with Serial Capture Affinity Purification
Authors: Liu Xingyu , Zhang Ying , Wen Zhiui , Hao Yan , Banks Charles , Lange Jeffrey J , Slaughter Brian , Unruh Jay , Florens Laurence , Abmayr Susan , Workman Jerry , Washburn Michael
Published: April 2020

Streamlined characterization of protein complexes remains a challenge for the study of protein interaction networks. Here, we describe Serial Capture Affinity Purification (SCAP) where two separate proteins are tagged with either the HaloTag or the SNAP-tag, permitting a multi-step affinity enrichment of specific protein complexes. The multifunctional capabilities of these protein tagging systems also permit in vivo validation of interactions using FRET and FCCS quantitative imaging. When coupling SCAP to cross-linking mass spectrometry, an integrated structural model of the complex of interest can be generated. We demonstrate this approach using the Spindlin1 and SPINDOC chromatin associated protein complex, culminating in a structural model with two SPINDOC docked on one SPIN1 molecule. In this model, SPINDOC interacts with the SPIN1 interface previously shown to bind a lysine and arginine methylated sequence of histone H3 Taken together, we present an integrated affinity purification, live cell imaging, and cross linking mass spectrometry approach for the building of integrative structural models of protein complexes.
Interaction capacity underpins community diversity
Authors: Ushio Masayuki
Published: April 2020

How patterns in community diversity emerge is a long-standing question in ecology. Theories and experimental studies suggested that community diversity and interspecific interactions are interdependent. However, evidence from multitaxonomic, high-diversity ecological communities is lacking because of practical challenges in characterizing speciose communities and their interactions. Here, I analyzed time-varying causal interaction networks that were reconstructed using 1197 species, DNA-based ecological time series taken from experimental rice plots and empirical dynamic modeling, and show that species interaction capacity, namely, the sum of interaction strength that a single species gives and receives, underpins community diversity. As community diversity increases, the number of interactions increases exponentially but the mean species interaction capacity of a community becomes saturated, weakening interaction among species. These patterns are explicitly modeled with simple mathematical equations, based on which I propose the “interaction capacity hypothesis,” namely, that species interaction capacity and network connectance are proximate drivers of community diversity. Furthermore, I show that total DNA copy number and temperature influence species interaction capacity and connectance nonlinearly, explaining a large proportion of diversity patterns observed in various systems. The interaction capacity hypothesis enables mechanistic explanations of community diversity, and how species interaction capacity is determined is a key question in ecology.
Average semivariance yields accurate estimates of the fraction of marker-associated genetic variance and heritability in complex trait analyses
Authors: Feldmann Mitchell J. , Piepho Hans-Peter , Bridges William C , Knapp Steven J.
Published: April 2020

The development of genome-informed methods for identifying quantitative trait loci (QTL) and studying the genetic basis of quantitative variation in natural and experimental populations has been driven by advances in high-throughput genotyping. For many complex traits, the underlying genetic variation is caused by the segregation of one or more 'large-effect' loci, in addition to an unknown number of loci with effects below the threshold of statistical detection. The large-effect loci segregating in populations are often necessary but not sufficient for predicting quantitative phenotypes. They are, nevertheless, important enough to warrant deeper study and direct modelling in genomic prediction problems. We explored the accuracy of statistical methods for estimating the fraction of marker-associated genetic variance (p) and heritability (H^2_M) for large-effect loci underlying complex phenotypes. We found that commonly used statistical methods overestimate p and H^2_M. The source of the upward bias was traced to inequalities between the expected values of variance components in the numerators and denominators of these parameters. Algebraic solutions for bias-correcting estimates of p and H^2_M were found that only depend on the degrees of freedom and are constant for a given study design. We discovered that average semivariance methods, which have heretofore not been used in complex trait analyses, yielded unbiased estimates of p and H^2_M, in addition to best linear unbiased predictors of the additive and dominance effects of the underlying loci. The cryptic bias problem described here is unrelated to selection bias, although both cause the overestimation of p and H^2_M. The solutions we described are predicted to more accurately describe the contributions of large-effect loci to the genetic variation underlying complex traits of medical, biological, and agricultural importance.
Origin and Evolution of DNA methyltransferases (DNMT) along the tree of life: A multi-genome survey
Authors: Bhattacharyya Madhumita , De Subhajyoti , Chakrabarti Saikat
Published: April 2020

Background

Cytosine methylation is a common DNA modification found in most eukaryotic organisms including plants, animals, and fungi. (Cytosine-5)-DNA methyltransferases (C5-DNA MTases) belong to the DNMT family of enzymes that catalyze the transfer of a methyl group from S-adenosyl methionine (SAM) to cytosine residues of DNA. In mammals, four members of the DNMT family have been reported: DNMT1, DNMT3a, DNMT3b and DNMT3L, but only DNMT1, DNMT3a and DNMT3b possess methyltransferase activity. There have been many reports about the methylation landscape in different organisms yet there is no systematic report of how the enzyme DNA (C5) methyltransferases have evolved in different organisms.

Result

DNA methyltransferases are found to be present in all three domains of life. However, significant variability has been observed in length, copy number and sequence identity when compared across kingdoms. Sequence conservation is greatly increased in invertebrates and vertebrates compared to other groups. Similarly, sequence length has been found to be increased while domain lengths remain more or less conserved. Vertebrates are also found to be associated with more conserved DNMT domains. Finally, comparison between single nucleotide polymorphisms (SNPs) prevailing in human populations and evolutionary changes in DNMT vertebrate alignment revealed that most of the SNPs were conserved in vertebrates.

Conclusion

The sequences (including the catalytic domain and motifs) and structure of the DNMT enzymes have been evolved greatly from bacteria to vertebrates with a steady increase in complexity and specificity. This study provides a systematic report of the evolution of DNA methyltransferase enzyme across different lineages of tree of life.