bluuebunny/crossref_metadata_2025 huggingface dataset:
Spectropolarimetry of magnetic Chemically Peculiar stars in the Orion OB1 association
Authors: Semenko Eugene , Romanyuk Iosif , Yakunin Ilya , Kudryavtsev Dmitry , Moiseeva Anastasiya
Published: July 2022

We summarize the results of a spectropolarimetric survey of 56 chemically peculiar (CP) stars in the association of Orion OB1. We uniformly collected the observational material with the 6-m telescope BTA of the Special Astrophysical Observatory in 2013–2021. We identify 14 new magnetic CP stars with a longitudinal magnetic field exceeding approximately 500 G. The studied sample contains 31 magnetic stars or 55 per cent of the whole CP population in Orion OB1. We show that the percentage of the magnetic CP stars and the field strength drop sharply with age. The mean longitudinal magnetic field in the young subgroup OB1b (log t = 6.23) is confidently almost three times stronger than in the older subgroups OB1a (log t = 7.05) and OB1c (log t = 6.66). In the Orion Nebula, a place with the youngest stellar population (log t < 6.0), we detect the magnetic field only in 20 per cent of CP stars. Such an occurrence drastically differs from 83 per cent of magnetic CP stars in the nearby subgroup OB1c. We consider this effect an observational bias caused by a significant portion of a very young population with the signatures of Herbig Ae/Be stars. The technique we used for magnetic measurements and the quality of available data do not allow us to detect weak fields in the case of stars with a limited number of lines and emissions in spectra.
Antibiotics for Preventing Recurrent Urinary Tract Infection: Systematic Review and Meta-analysis
Authors: Jent Philipp , Berger Julia , Kuhn Annette , Trautner Barbara W , Atkinson Andrew , Marschall Jonas
Published: July 2022

Recurrent urinary tract infections are a common health problem. The only comprehensive synthesis on antibiotic prophylaxis in the last 15 years has been a guideline-embedded meta-analysis. We conducted a systematic review and meta-analysis of randomized controlled trials published up to October 13, 2020, evaluating patients age ≥12 years with either ≥2 episodes of lower urinary tract infection (UTI) within 6 months or ≥3 in the past year. Placebo or antibiotics were allowed as comparators. Study quality was low. In the 11 placebo-controlled trials, the risk for developing UTI was 85% lower with prophylaxis in comparison with placebo (risk ratio [RR], 0.15; 95% CI, 0.08–0.29). In the 9 head-to-head trials, the efficacy of the antibiotic agents appeared similar: The pooled RR indicated no difference between nitrofurantoin and comparators (RR, 1.01; 95% CI, 0.74–1.37), nor trimethoprim (+/- sulfamethoxazole; RR, 1.34; 95% CI, 0.89–2.03) or norfloxacin and comparators (RR, 1.17; 95% CI, 0.43–1.70). Studies comparing intermittent (postcoital) with continuous strategies revealed intermittent application to be equally effective.
RADIOPROTECTION SURVEILLANCE OF THE TJ-II OPERATION BY TLD
Authors: Noguerales C , Álvarez A , Ascasibar E , Carrasco R , Liniers M , Medrano M , Rodríguez-Rodrigo L , Vico A
Published: July 2022

The TJ-II stellarator presently in operation at the National Laboratory of Fusion is subject to radiological surveillance in compliance with the Spanish Nuclear Regulation. During its pulsed operation hard X-rays are emitted by the runaway electrons, and soft X-rays are generated by bremsstrahlung of thermalized electrons. Inside the experimental hall, the plasma heating systems and some active diagnostics are additional sources of radiation. Outside the experimental hall, some auxiliary systems, such as high-voltage power supplies, must be checked for radiological influence. In order to verify the adequate radiological classification of the different working areas, 15 dosemeters are distributed in radiologically controlled areas close to the machine, as well as in areas of public use in the TJ-II building. The integrated dose equivalent is analyzed to help establish the range of radiological influence of the stellarator. The results of the period 2015–20 are presented and analyzed.
Scoring sleep with artificial intelligence enables quantification of sleep stage ambiguity: hypnodensity based on multiple expert scorers and auto-scoring
Authors: Bakker Jessie P , Ross Marco , Cerny Andreas , Vasko Ray , Shaw Edmund , Kuna Samuel , Magalang Ulysses J , Punjabi Naresh M , Anderer Peter
Published: July 2022

Study Objectives

To quantify the amount of sleep stage ambiguity across expert scorers and to validate a new auto-scoring platform against sleep staging performed by multiple scorers.

Methods

We applied a new auto-scoring system to three datasets containing 95 PSGs scored by 6–12 scorers, to compare sleep stage probabilities (hypnodensity; i.e. the probability of each sleep stage being assigned to a given epoch) as the primary output, as well as a single sleep stage per epoch assigned by hierarchical majority rule.

Results

The percentage of epochs with 100% agreement across scorers was 46 ± 9%, 38 ± 10% and 32 ± 9% for the datasets with 6, 9, and 12 scorers, respectively. The mean intra-class correlation coefficient between sleep stage probabilities from auto- and manual-scoring was 0.91, representing excellent reliability. Within each dataset, agreement between auto-scoring and consensus manual-scoring was significantly higher than agreement between manual-scoring and consensus manual-scoring (0.78 vs. 0.69; 0.74 vs. 0.67; and 0.75 vs. 0.67; all p < 0.01).

Conclusions

Analysis of scoring performed by multiple scorers reveals that sleep stage ambiguity is the rule rather than the exception. Probabilities of the sleep stages determined by artificial intelligence auto-scoring provide an excellent estimate of this ambiguity. Compared to consensus manual-scoring, sleep staging derived from auto-scoring is for each individual PSG noninferior to manual-scoring meaning that auto-scoring output is ready for interpretation without the need for manual adjustment.
Imaging in the Evaluation of Esophageal Trauma Including Surgery
Authors: Salehpoor Ali , Shiehmorteza Masoud , Terrazas Martha , Thompson William
Published: July 2022

Esophageal perforation and anastomotic leak of the postsurgical esophagus place patients at significant risk for morbidity and mortality, requiring prompt and accurate diagnosis through imaging. Plain radiographs may be obtained during the initial evaluation of symptoms but have low sensitivity and specificity for esophageal perforation. With clinical suspicion for perforation, CT with oral contrast should be obtained initially due to its high sensitivity, utility in surgical planning, and usefulness in evaluating underlying causes or other etiologies for symptoms. With a negative CT, perforation is ruled out and subsequent fluoroscopic esophagography is unnecessary. In patients with postsurgical anatomy such as esophagectomy, diagnosis is difficult and concurrent review of CT and fluoroscopy is more sensitive than either modality alone.
Nutrition management and pancreatitis in children: new insights
Authors: Dike Chinenye R. , Abu-El-Haija Maisam
Published: July 2022

Recent findings

Early initiation of feeds is safe and possible in mild to moderate pediatric acute pancreatitis (AP) and is not associated with increased pain or increased serum lipase level. Enteral nutrition within 48 h of admission compared to no feeds within 48 h (NPO) is associated with a significant reduction in length of stay, reduced progression to severe acute pancreatitis, decreased ICU transfers, and increased weight gain at follow-up. Early standard fat meals did not worsen pain or serum lipase levels in children with mild to moderate AP.

Purpose of review

Nutrition is essential in the management of AP in children. Diet before, during, and after an attack of AP can affect outcomes. Here, we highlight recent advances that have been made in the last decade on nutritional interventions in pediatric acute pancreatitis and provide future directions for research.

Early enteral nutrition is safe and feasible in pediatric mild to moderate AP and is associated with improved outcomes. There are only a handful of studies on nutritional interventions in pediatric mild to moderate AP. Further studies are needed to understand the effects of early enteral nutrition in pediatric severe AP.
Association of Unilateral Latissimus Dorsi Muscle Harvest for Breast Reconstruction with Postoperative Spinal Posture
Authors: Kim Jisu , Lee Hojune , Pyon Jai-Kyong , Mun Goo-Hyun , Bang Sa Ik , Jeon Byung-Joon , Lee Kyeong-Tae
Published: July 2022

Background:

The latissimus dorsi (LD) muscle originates from the lower thoracic spine with broad attachment and plays a subsidiary role in spinal postural stability. We investigated whether harvesting unilateral LD muscle for breast reconstruction could influence spinal posture in the long-term.

Methods:

Patients who underwent immediate unilateral breast reconstruction between 2002 and 2010 were reviewed. They were grouped according to reconstruction methods: LD muscle flap and tissue expander/implant. The Cobb angle was assessed twice at each of five different time points (preoperative/postoperative 2, 4, 6, and 8 years) by an independent physician blinded to the reconstruction modality. Postoperative scoliosis was defined as a mean Cobb angle >10° at 8 years postoperatively. The trends of changes in Cobb angle over time and the rate of postoperative scoliosis were compared between reconstruction methods.

Results:

In total, 153 women were analyzed, including 102 using LD muscle flap and 51 using tissue expander/implant, with a median follow-up of 103.0 months. The LD flap group showed enhanced trends of increasing postoperative Cobb angles as compared with the tissue expander/implant group, and the difference remained significant after adjusting for other variables (p = 0.001). The rate of postoperative scoliosis was significantly higher in the LD flap group than in the control group (p = 0.029). Multivariable analyses revealed that use of the LD flap was associated with a significantly increased rate of postoperative scoliosis.

Conclusions:

Unilateral LD muscle flap harvest for breast reconstruction might be associated with changes of spinal posture in the long run.
“Introduction of a low-cost and automated four-dimensional assessment system of the face.”
Authors: Petrides George A. , Joy Christopher , Dolk Oliver , Low Tsu-Hui (Hubert) , Lovell Nigel , Eviston Timothy J.
Published: July 2022

Existing automated objective grading systems either fail to consider the face’s complex 3D morphology or suffer from poor feasibility and usability. Consumer-based Red Green Blue Depth (RGB-D) sensors and/or smartphone integrated 3D hardware can inexpensively collect detailed four-dimensional facial data in real-time but are yet to be incorporated into a practical system. This study aims to evaluate the feasibility of a proof-of-concept automated 4D facial assessment system using an RGB-D sensor (termed OpenFAS) for use in a standard clinical environment. This study was performed on normal adult volunteers and patients with facial nerve palsy (FNP). The setup consists of the Intel RealSense SR300 connected to a laptop running the OpenFAS application. The subject sequentially mimics the facial expressions shown on screen. Each frame is landmarked, and automatic anthropometric calculations are performed. Any errors during each session were noted. Landmarking accuracy was estimated by comparing the ‘ground-truth position’ of landmarks annotated manually to those placed automatically. 18 participants were included in the study, nine healthy participants and nine patients with FNP. Each session was standardized at approximately 106 seconds. 61.8% of landmarks were automatically annotated within approximately 1.575mm of their ground-truth locations. Our findings support that OpenFAS is usable and feasible in routine settings, laying down the critical groundwork for a facial assessment system that addresses the shortcomings of existing tools. However, the iteration of OpenFAS presented in this study is undoubtedly nascent with future work including improvements to landmarking accuracy, analyses components, and RGB-D technology required before clinical application.
M3CV:A Multi-subject, Multi-session, and Multi-task database for EEG-based Biometrics Challenge
Authors: Huang Gan , Hu Zhenxing , Chen Weize , Liang Zhen , Li Linling , Zhang Li , Zhang Zhiguo
Published: July 2022

EEG signals exhibit commonality and variability across subjects, sessions, and tasks. But most existing EEG studies focus on mean group effects (commonality) by averaging signals over trials and subjects. The substantial intra- and inter-subject variability of EEG has often been overlooked. The recently significant technological advances in machine learning, especially deep learning, have brought technological innovations to EEG signal application in many aspects, but there are still great challenges in cross-session, cross-task, and cross-subject EEG decoding. In this work, an EEG-based biometric competition based on a large-scale M3CV (A Multi-subject, Multi-session, and Multi-task Database for investigation of EEG Commonality and Variability) database was launched to better characterize and harness the intra- and inter-subject variability and promote the development of machine learning algorithm in this field. In the M3CV database, EEG signals were recorded from 106 subjects, of which 95 subjects repeated two sessions of the experiments on different days. The whole experiment consisted of 6 paradigms, including resting-state, transient-state sensory, steady-state sensory, cognitive oddball, motor execution, and steady-state sensory with selective attention with 14 types of EEG signals, 120,000 epochs. With the learning tasks of the identification and verification, the performance metrics and baseline methods were introduced in the competition. In general, the proposed M3CV dataset and the EEG-based biometric competition aim to provide the opportunity to develop advanced machine learning algorithms for achieving an in-depth understanding of the commonality and variability of EEG signals across subjects, sessions, and tasks.
Modulating hierarchical learning by high-definition transcranial alternating current stimulation at theta frequency
Authors: Liu Meng , Dong Wenshan , Wu Yiling , Verbeke Pieter , Verguts Tom , Chen Qi
Published: July 2022

Considerable evidence highlights the dorsolateral prefrontal cortex (DLPFC) as a key region for hierarchical (i.e., multi-level) learning. In a previous electroencephalography (EEG) study we found that the low-level prediction errors (PEs) were encoded by frontal theta oscillations (4–7Hz), centered on right DLPFC (rDLPFC). However, the causal relationship between frontal theta oscillations and hierarchical learning remains poorly understood. To investigate this question, in the current study, participants received theta (6Hz) and sham high-definition transcranial alternating current stimulation (HD-tACS) over the rDLPFC, while performing the probabilistic reversal learning task. Behaviorally, theta tACS induced a significant reduction in accuracy for the stable environment, but not for the volatile environment, relative to the sham condition. Computationally, we implemented a combination of a hierarchical Bayesian learning and a decision model. Theta tACS induced a significant increase in low-level (i.e., probability-level) learning rate and uncertainty of low-level estimation relative to sham condition. Instead, the temperature parameter of the decision model, which represents (inverse) decision noise, was not significantly altered due to theta stimulation. These results indicate that theta frequency may modulate the (low-level) learning rate. Furthermore, environmental features (e.g., its stability) may determine whether learning is optimized as a result.
Emergence of persistent and sequential representations in the hippocampal-prefrontal circuitry during associative learning
Authors: Souza Bryan C. , Klee Jan L. , Mazzucato Luca , Battaglia Francesco P.
Published: July 2022

Temporal associations between sensory stimuli separated in time rely on the interaction between the hippocampus and medial prefrontal cortex (mPFC). However, it is not known how changes in their neural activity support the emergence of temporal association learning. Here, we use simultaneous electrophysiological recordings in the hippocampal CA1 region and mPFC of mice to elucidate the neural dynamics underlying memory formation in an auditory trace conditioning task. We found that in both areas conditioned (CS+/CS−) and unconditioned stimuli (US) evoked similar temporal sequences of neural responses that progressively diverged during learning. Additionally, persistent CS representations emerged in mPFC after learning, supported by CS+ coding states whose transient reactivation reliably predicted lick onset and behavioral performance on single trials. These results show that coordination of temporal sequences in CA1 and persistent activity in mPFC may underlie temporal association learning, and that transient reactivations of engrams in mPFC predict the animal behavior.

Highlights

Temporal representation of CS+, but not CS− and US, strengthens in CA1 after learning.

Similarity between stimulus and reward temporal representations decrease with learning, but is recovered in error trials.

Representation of stimulus identity is strong and stable in PFC since stimulus onset, while it only emerges in CA1 during trace period.

Neural states defined on faster time-scales reveal the emergence of CS coding states in PFC whose onset predicts lick times and task performance.

PFC-CA1 states do not increase coordination during late CS+ stimulus and trace.

Abstract Figure

Figure 0:

Graphical Abstract
Subthalamic stimulation evoked cortical responses relate to motor performance in Parkinson’s disease
Authors: Bahners Bahne H. , Spooner Rachel K. , Hartmann Christian J. , Schnitzler Alfons , Florin Esther
Published: July 2022

Subthalamic deep brain stimulation is effective in alleviating motor symptoms in Parkinson’s disease. Establishing the clinically best stimulation settings often requires time-consuming test sessions and creates a need for biomarkers to optimize this process. While stimulation-evoked cortical responses have been proposed as such a neurophysiological marker, their relationship to motor performance has not yet been studied systematically. For this aim, we recorded finger-tapping movements and cortical responses evoked by different stimulation amplitudes of 22 patients with Parkinson’s disease using magnetoencephalography. The motor cortex amplitude was a significant predictor of a higher finger tap frequency and a more regular tapping profile. In addition, subthalamic stimulation evoked responses in the inferior and middle frontal gyrus, and the supplementary motor area. While earlier studies relied on a limited cortical coverage, we reveal a cortical distribution of responses that aligns with the basal ganglia-thalamo-cortical network. Our study sheds light on the relationship between cortical responses evoked by subthalamic stimulation and motor performance based on objective quantitative parameters. Stimulation-evoked responses could guide clinical programming in the future.
A short-term decellularisation technique for porcine carotid arteries that conveys a structural stimulus to cells
Authors: Fitzpatrick E. , Gaul R. , Smekens C. , Mathieu P. , Meehan B. , Tornifoglio B. , Cahill P.A. , Lally C.
Published: July 2022

In many cases, treatment for stenotic atherosclerotic lesions requires the use of bypass grafts to divert blood flow around the diseased vessel sections. Autologous vessels are considered the “gold standard” for bypass conduits; however, the shortage of healthy autologous vessels has resulted in an increasing focus on optimising synthetic, biological and/or tissue engineered vascular bypass grafts. While many of the previously published methods have been shown to fall short of producing an ideal TEVG, this report presents a decellularisation process that produces an acellular vascular graft that is efficient, cost effective, and could be readily automated. The resulting graft can be used “off the shelf”, has preserved arterial structure and mechanical properties, and conforms to decellularisation criteria regarding the sufficient removal of cellular and genetic components. Additionally, the graft does not require any priming, supports molecular transport, can withstand supraphysiological pressures, and can support cell attachment and growth under physiological strain conditions whilst providing structural cues for cell adhesion and growth.

Impact statement

Vascular disease remains the leading cause of mortality worldwide. In the absence of suitable autologous vessels, there currently exists a clear clinical need for ‘off the shelf’ vascular grafts that can successfully bypass diseased arteries. This paper outlines a short-term method for obtaining such a graft. The technique used involves decellularising porcine carotid arteries whilst preserving arterial structure and mechanical properties and is compliant with the international standard for implantable vascular prostheses: EN ISO 7198:2017. Additionally, this protocol is cost and time effective, and produces reproducible “ready to use” acellular grafts that support molecular transport, can withstand supraphysiological pressures, and can support cell attachment and growth with controlled structural cues under physiological strain conditions.
Improving Memory via Automated Targeted Memory Reactivation during Sleep
Authors: Whitmore Nathan W. , Harris Jasmine C. , Kovach Torin , Paller Ken A.
Published: July 2022

A widely accepted view in memory research is that previously acquired information can be reactivated during sleep, leading to persistent memory storage. Recently, Targeted Memory Reactivation (TMR) has been developed as a technique whereby specific memories can be reactivated during sleep using a sensory stimulus linked to prior learning. TMR can improve various types of memory, raising the possibility that it may be useful for cognitive enhancement and clinical therapy. A major challenge for the expanded use of TMR is that experimenters must manually control stimulation timing and intensity, which is impractical in most settings. To address this limitation, we developed the SleepStim system for automated TMR in the home environment. SleepStim includes a smartwatch to collect movement and heart-rate data, plus a smartphone to emit auditory cues. A machine-learning model identifies periods of deep non-REM sleep and triggers TMR sounds within these periods. We tested whether this system could replicate the spatial-memory benefit of in-lab TMR. Participants learned the locations of objects on a grid, and then half of the object locations were reactivated during sleep over three nights. In an experiment with 61 participants, the TMR effect was nonsignificant but varied systematically with stimulus intensity; low-intensity but not high-intensity stimuli produced memory benefits. In a second experiment with 24 participants, we limited stimulus intensity and found that TMR reliably improved spatial memory, consistent with effects observed in laboratory studies. We conclude that SleepStim can effectively accomplish automated TMR and that avoiding sleep disruption is critical for TMR benefits.
Mechanical vibration modulates regional cerebral blood flow and biomechanical co-variance network in a frequency-dependent manner
Authors: Kong Linghan , Qiu Suhao , Chen Yu , He Zhao , Huang Peiyu , He Qiang , Zhang Ru-Yuan , Feng Xi-Qiao , Deng Linhong , Li Yao , Yan Fuhua , Yang Guang-Zhong , Feng Yuan
Published: July 2022

Human brain experiences vibration of certain frequency during various physical activities such as vehicle transportation and machine operation or accidents, which may cause traumatic brain injury or other brain diseases. However, little is known about what happened to brain after vibration stimuli. Here, with a custom-built electromagnetic actuator, vibration was induced in the brain while cerebral blood flow (CBF) and brain stiffness were measured at 20, 30, 40 Hz for 52 healthy volunteers. With increasing frequency, multiple regions of the brain showed increasingly reduced CBF, while the size of such regions also expanded. The vibration-induced CBF reduction regions largely fell inside the brain’s default mode network (DMN), with about 58 or 46 % overlap at 30 or 40 Hz, respectively. By establishing a biomechanical co-variance network based on tissue stiffness, analysis of small-world properties and modularity showed an increased disruption of the network with increased frequency. These findings demonstrate frequency-dependent features of vibration modulation to brain. Furthermore, the overlap between CBF reduction regions and DMN, and the vibration-induced decrease of biomechanical network connections suggest a interweaved relationship between blood flow, tissue stiffness, and cognitive functions. These may provide critical insights into the mechanical stimulus to brain and vibration-induced brain pathologies.
In utero exposure to cannabidiol disrupts select early-life behaviors in a sex-specific manner
Authors: Iezzi Daniela , Caceres Alba , Chavis Pascale , Manzoni Olivier J.J.
Published: July 2022

Cannabidiol (CBD), one of the main components of cannabis, is generally considered safe, despite the lack of studies on the possible consequences of its consumption during critical periods of neurodevelopment, including prenatal life. Although CBD crosses the placenta and its use during pregnancy is steadily increasing, the impact of gestational CBD exposure on early life is unknown. Here, we combined behavioral exploration and deep learning to assess how in utero exposure to low doses of CBD alters pre-weaning behaviors in mouse pups of both sexes. The data reveal that pups from CBD-treated dams exhibit sex-specific alterations in weight growth, homing behavior, and the syllabic repertoire of ultrasonic vocalizations. Thus, prenatal CBD is associated with alterations in innate behavioral responses and communication skills.
USP30 inhibition induces mitophagy and reduces oxidative stress in parkin-deficient and CCCP-stressed human iPSC-derived neurons
Authors: Okarmus Justyna , Agergaard Jette Bach , Stummann Tina C. , Haukedal Henriette , Ambjørn Malene , Freude Kristine K. , Fog Karina , Meyer Morten
Published: July 2022

Ubiquitination of mitochondrial proteins plays an important role in the cellular regulation of mitophagy. The E3 ubiquitin ligase parkin (encoded by PARK2) and the ubiquitin-specific protease 30 (USP30) have both been reported to regulate ubiquitination of outer mitochondrial proteins and thereby mitophagy. Loss of E3 ligase activity is thought to be pathogenic in both sporadic and inherited Parkinson’s disease (PD), with loss-of-function mutations in PARK2 being the most frequent cause of autosomal recessive PD.

The aim of the present study was to evaluate whether mitophagy induced by USP30 inhibition provides a functional rescue in isogenic human induced pluripotent stem cell-derived dopaminergic neurons with and without PARK2 knockout (KO).

Our data show that healthy neurons responded to CCCP-induced mitochondrial damage by clearing the impaired mitochondria and that this process was accelerated by USP30 inhibition. Parkin-deficient neurons showed an impaired mitophagic response to CCCP challenge, although mitochondrial ubiquitination was enhanced. USP30 inhibition promoted mitophagy in PARK2 KO neurons, independently of whether left in basal conditions or treated with CCCP. In PARK2 KO, as in control neurons, USP30 inhibition balanced oxidative stress levels by reducing excessive production of reactive oxygen species. Interestingly, non-dopaminergic neurons, were the main driver of the beneficial effects of USP30 inhibition.

Our findings demonstrate that USP30 inhibition is a promising approach to boost mitophagy and improve cellular health, also in parkin-deficient cells, and support the potential relevance of USP30 inhibitors as a novel therapeutic approach in diseases with a need to combat neuronal stress mediated by impaired mitochondria.
Decoupling of interacting neuronal populations by time-shifted stimulation through spike-timing-dependent plasticity
Authors: Asl Mojtaba Madadi , Valizadeh Alireza , Tass Peter A.
Published: July 2022

The synaptic organization of the brain is constantly modified by activity-dependent synaptic plasticity. In several neurological disorders, abnormal neuronal activity and pathological synaptic connectivity may significantly impair normal brain function. Reorganization of neuronal circuits by therapeutic stimulation has the potential to restore normal brain dynamics. Increasing evidence suggests that the temporal stimulation pattern crucially determines the long-lasting therapeutic effects of stimulation. Here, we tested whether a specific pattern of brain stimulations can enable the suppression of pathologically strong inter-population synaptic connectivity through spike-timing-dependent plasticity (STDP). More specifically, we tested how introducing a time shift between stimuli delivered to two interacting populations of neurons can effectively decouple them. To that end, we first used a tractable model, i.e., two bidirectionally coupled leaky integrate-and-fire (LIF) neurons, to theoretically analyze the optimal range of stimulation frequency and time shift for decoupling. We then extended our results to two reciprocally connected neuronal populations (modules) where inter-population delayed connections were modified by STDP. As predicted by the theoretical results, appropriately time-shifted stimulation causes a decoupling of the two-module system through STDP, i.e., by unlearning pathologically strong synaptic interactions between the two populations. Based on the overall topology of the connections, the decoupling of the two modules, in turn, causes a desynchronization of the populations that outlasts the cessation of stimulation. Decoupling effects of the time-shifted stimulation can be realized by time-shifted burst stimulation as well as time-shifted continuous simulation. Our results provide insight into the further optimization of a variety of multichannel stimulation protocols aiming at a therapeutic reshaping of diseased brain networks.
Sclerostin influences exercise-induced adaptations in body composition and white adipose tissue morphology in male mice
Authors: Kurgan N , Stoikos J , Baranowski BJ , Yumol J , Dhaliwal R , Sweezey-Munroe JB , Fajardo VA , Gittings W , MacPherson REK , Klentrou P
Published: July 2022

Sclerostin is an inhibitor of the osteogenic Wnt/β-catenin signalling pathway that has an endocrine role in regulating adipocyte differentiation and metabolism. Additionally, subcutaneous white adipose tissue (scWAT) sclerostin content decreases following exercise training (EXT). Therefore, we hypothesized that EXT-induced reductions in adipose tissue sclerostin may play a role in regulating adaptations in body composition and whole-body metabolism. To test this hypothesis, 10-week-old male C57BL/6J mice were either sedentary (SED) or performing 1h of treadmill running at ∼65-70% VO2max 5 d/week (EXT) for 4 weeks and had subcutaneous (s.c) injections of either saline (C) or recombinant sclerostin (S) (0.1 mg/kg body mass) 5 d/week; thus, making 4 groups (SED-C, EXT-C, SED-S, and EXT-S; n=12/group). No differences in body mass were observed between experimental groups, while food intake was higher in EXT (p=0.03) and S (p=0.08) groups. There was a higher resting energy expenditure in all groups compared to SED-C. EXT-C had a higher lean mass and lower fat mass percentage compared to SED-C and SED-S. No differences in body composition were observed in either the SED-S or EXT-S groups. Lower scWAT (inguinal), vWAT (epididymal) mass, and scWAT adipocyte cell size and increased percentage of multilocular cells in scWAT were observed in the EXT-C group compared to SED-C, while lower vWAT was only observed in the EXT-S group. EXT mice had increased iWAT Lrp4 and mitochondrial content and sclerostin treatment only inhibited increased Lrp4 content with EXT. Together, these results provide evidence that reductions in resting sclerostin with exercise training may influence associated alterations in energy metabolism and body composition, particularly in scWAT.
CanSeer: A Method for Development and Clinical Translation of Personalized Cancer Therapeutics
Authors: Butt Rida Nasir , Amina Bibi , Sultan Muhammad Umer , Tanveer Zain Bin , Hussain Risham , Akbar Rida , Khan Salaar , Gondal Mahnoor Naseer , Khalid Muhammad Farhan , Faisal Amir , Shoaib Muhammad , Chaudhary Safee Ullah
Published: July 2022

Computational modeling and analysis of biomolecular network models annotated with cancer patient-specific multi-omics data can enable the development of personalized therapies. Current endeavors aimed at employingin silicomodels towards personalized cancer therapeutics remain to be fully translated. In this work, we present “CanSeer” a novel multi-stage methodology for developingin silicomodels towards clinical translation of personalized cancer therapeutics. The proposed methodology integrates state-of-the-art dynamical analysis of biomolecular network models with patient-specific genomic and transcriptomic data to assess the individualized therapeutic responses to targeted drugs and their combinations.CanSeer’stranslational approach employs transcriptomic data (RNA-seq based gene expressions) with genomic profile (CNVs, SMs, and SVs). Specifically, patient-specific cancer driver genes are identified, followed by the selection of druggable and/or clinically actionable targets for therapeutic interventions. To exemplifyCanSeer, we have designed three case studies including (i) lung squamous cell carcinoma, (ii) breast invasive carcinoma, and (iii) ovarian serous cystadenocarcinoma. The case study on lung squamous cell carcinoma concluded that restoration of Tp53 activity together with an inhibition of EGFR as an efficacious combinatorial treatment for patients with Tp53 and EGFR cancer driver genes. The findings from the cancer case study helped identify personalized treatments including APR-246, APR-246+palbociclib, APR-246+osimertinib, APR-246+afatinib, APR-246+osimertinib+dinaciclib, and APR-246+afatinib+dinaciclib. The second case study on breast invasive carcinoma revealedCanSeer’s potential to elucidate drug resistance against targeted drugs and their combinations including KU-55933, afuresertib, ipatasertib, and KU-55933+afuresertib. Lastly, the ovarian cancer case study revealed the combinatorial efficacy of APR-246+carmustine, and APR-246+dinaciclib for treating ovarian serous cystadenocarcinoma. Taken together,CanSeeroutlines a novel method for systematic identification of optimal tailored treatments with mechanistic insights into patient-to-patient variability of therapeutic response, drug resistance mechanism, and cytotoxicity profiling towards personalized medicine.
Decision-making processes in perceptual learning depend on effectors
Authors: Ivanov Vladyslav , Manenti Giorgio L. , Plewe Sandrin S. , Kagan Igor , Schwiedrzik Caspar M.
Published: July 2022

Visual perceptual learning is traditionally thought to arise in visual cortex. However, typical perceptual learning tasks also involve systematic mapping of visual information onto motor actions. Because the motor system contains both effector-specific and effector-unspecific representations, the question arises whether visual perceptual learning is effector-specific itself, or not. Here, we study this question in an orientation discrimination task. Subjects learn to indicate their choices either with joystick movements or with manual reaches. After training, we challenge them to perform the same task with eye movements. We dissect the decision-making process using the drift diffusion model. We find that learning effects on the rate of evidence accumulation depend on effectors, albeit not fully. This suggests that during perceptual learning, visual information is mapped onto effector-specific integrators. Overlap of the populations of neurons encoding motor plans for these effectors may explain partial generalization. Taken together, visual perceptual learning is not limited to visual cortex, but also affects sensorimotor mapping at the interface of visual processing and decision making.
Sex-Specific Effects of Early-Life Iron Deficiency and Prenatal Choline Treatment on Adult Rat Hippocampal Transcriptome
Authors: Liu Shirelle X. , Fredrickson Tenille K. , Mancipe Natalia Calixto , Georgieff Michael K. , Tran Phu V.
Published: July 2022

Background

Fetal-neonatal iron deficiency (ID) causes long-term neurocognitive and affective dysfunctions. Clinical and preclinical studies have shown that early-life ID produces sex-specific effects. However, little is known about the molecular mechanisms underlying these early-life ID-induced sex-specific effects on neural gene regulation.

Objective

To illustrate sex-specific transcriptome alteration in adult rat hippocampus induced by fetal-neonatal ID and prenatal choline treatment.

Methods

Pregnant rats were fed an iron-deficient (4 mg/kg Fe) or iron-sufficient (200 mg/kg Fe) diet from gestational day (G) 2 to postnatal day (P) 7 with or without choline supplementation (5 g/kg choline) from G11-18. Hippocampi were collected from P65 offspring of both sexes and analyzed for changes in gene expression.

Results

Both early-life ID and choline treatment induced transcriptional changes in adult female and male rat hippocampus. Both sexes showed ID-induced alterations in gene networks leading to enhanced neuroinflammation. In females, ID-induced changes indicating enhanced activity of oxidative phosphorylation and fatty acid metabolism, which are contrary to the ID effect in males. Prenatal choline supplementation induced the most robust changes in gene expression, particularly in the iron-deficient animals where it partially rescued ID-induced dysregulations. Choline supplementation also altered hippocampal transcriptome in the iron-sufficient rats with indications for both beneficial and adverse effects.

Conclusions

This study provided unbiased global assessments of gene expression regulated by iron and choline status in a sex-specific manner, with greater effects in female than male rats. Our new findings highlight potential sex-specific gene networks regulated by iron and choline status for further investigation.
Terminal flourishes but not trills differ between urban and rural chaffinch song
Authors: Yelimlieş Alper , Atalas Berkay , Önsal Çağla , Akçay Çağlar
Published: July 2022

Anthropogenic noise interrupts the acoustic communication between animals living in urban habitats. Accumulating evidence suggests that animals can evade this interruption using various strategies such as shifting frequencies upwards or increasing the duration of their signals. In this study, we compared the time and frequency-related characteristics of songs and rain calls of common chaffinches (Fringilla coelebs) inhabiting rural forests and an urban park in Turkey. Most of the song phrases and rain calls did not differ in any of the characteristics measured between urban and rural chaffinches. Terminal flourish phrases of the songs, however, had lower minimum frequencies and broader bandwidth in urban territories, contrary to our predictions. We discuss this finding in relation to its potential adaptive significance.
Cell type- and state- resolved immune transcriptomic profiling identifies glucocorticoid-responsive molecular defects in multiple sclerosis T cells
Authors: Roostaei Tina , Sabrin Afsana , Kivisäkk Pia , McCabe Cristin , Nejad Parham , Felsky Daniel , Touil Hanane , Vlachos Ioannis S. , Hui Daniel , Fransson Jennifer , Patsopoulos Nikolaos A. , Kuchroo Vijay K. , Zujovic Violetta , Weiner Howard L. , Klein Hans-Ulrich , De Jager Philip L.
Published: July 2022

The polygenic and multi-cellular nature of multiple sclerosis (MS) immunopathology necessitates cell-type-specific molecular studies in order to improve our understanding of the diverse mechanisms underlying immune cell dysfunction in MS. Here, by generating a dataset of 1,075 transcriptomes from 209 participants (167 MS and 42 healthy), we assessed MS-associated transcriptional changes in six implicated cell-type-states: naïve and memory helper T cells and classical monocytes purified from peripheral blood, each in their primary (ex vivo, unstimulated) andin vitrostimulated states. Our data suggest that primary profiles show larger MS-associated differences than the post-stimulation contexts. We further identified shared and distinct changes in individual genes, biological pathways, and co-expressed gene modules in MS T cells and monocytes, and prioritized genes such asZBTB16as MS-associated regulators in both cell types. Of six identified MS-associated co-expressed gene modules, three (two lymphoid and one myeloid) were replicated in independent data from peripheral blood mononuclear cells (PBMC) and monocyte-derived macrophages. A subsequentin silicodrug screen prioritized small-molecule compounds for reversing the perturbation of the MS-associated modules. The effects of glucocorticoid receptor agonists as the top-identified therapeutic class for the replicated T cell modules were validated using targetedin silicoanalyses andin vitroexperiments, suggesting the coordinated dysregulation of glucocorticoid-responsive genes in MS T cells. In summary, our study identifies and validates individual genes and co-expressed gene modules from T and myeloid cells that are perturbed in MS, offering new targets for therapeutic discovery and biomarker development to guide the management of MS.
A brain-wide form of presynaptic active zone plasticity orchestrates resilience to brain aging in Drosophila
Authors: Huang Sheng , Piao Chengji , Beuschel Christine B. , Sigrist Stephan J.
Published: July 2022

The brain as a central regulator of stress integration determines what is threatening, stores memories and regulates physiological adaptations across the aging trajectory. While sleep homeostasis is linked to brain resilience, how age-associated changes intersect to adapt brain resilience remains enigmatic. We here provide evidence that a brain-wide form of presynaptic active zone plasticity (“PreScale”) promotes resilience by coupling sleep, longevity and memory during aging. PreScale increased until mid-age and contributed to the age-adaption of sleep patterns, in effect promoting longevity but not memory of aging flies. Mechanistically, imaging and electrophysiology suggest that genetically-encoded PreScale reprograms neuronal activity, membrane firing patterns and excitability of the sleep-promoting dorsal fan-shaped body neurons, qualitatively similar to aging. Flies metabolically reprogrammed by spermidine towards extended longevity and preserved memory skipped PreScale and subsequently age-associated sleep pattern changes. Acute deep sleep induction in mid-age flies reset PreScale back to juvenile levels and restored memory. Taken together, early along aging trajectory, PreScale seems to steer trade-offs between longevity and memory, illustrating how life strategy manifests on circuit and synaptic plasticity levels.

GRAPHIC ABSTRACT

Presynaptic plasticity at the active zone (AZ) during early aging triggers sleep pattern changes, and subsequently steers trade-offs between memory formation and longevity. Interventions like spermidine (Spd) and Gaboxadol (THIP) supplementation suppress PreScale and allow for new memory formation and lifespan extension.
Structural spine plasticity: learning and forgetting of odor-specific subnetworks in the olfactory bulb
Authors: Meng John Hongyu , Riecke Hermann
Published: July 2022

Learning to discriminate between different sensory stimuli is essential for survival. In rodents, the olfactory bulb, which contributes to odor discrimination via pattern separation, exhibits extensive structural synaptic plasticity involving the formation and removal of synaptic spines, even in adult animals. The network connectivity resulting from this plasticity is still poorly understood. To gain insight into this connectivity we present here a computational model for the structural plasticity of the reciprocal synapses between the dominant population of excitatory principal neurons and inhibitory interneurons. It incorporates the observed modulation of spine stability by odor exposure. The model captures the striking experimental observation that the exposure to odors does not always enhance their discriminability: while training with similar odors enhanced their discriminability, training with dissimilar odors actually reduced the discriminability of the training stimuli (Chu et al, 2016). Strikingly, this differential learning does not require the activity-dependence of the spine stability and occurs also in a model with purely random spine dynamics in which the spine density is changed homogeneously, e.g., due to a global signal. However, the experimentally observed odor-specific reduction in the response of principal cells as a result of extended odor exposure (Kato et al. 2012) and the concurrent disinhibition of a subset of principal cells arise only in the activity-dependent model. Moreover, this model predicts the experimentally testable recovery of odor response through weak but not through strong odor re-exposure and the forgetting of odors via exposure to interfering odors. Combined with the experimental observations, the computational model provides strong support for the prediction that odor exposure leads to the formation of odor-specific subnetworks in the olfactory bulb.

Author Summary

A key feature of the brain is its ability to learn through the plasticity of its network. The olfactory bulb in the olfactory system is a remarkable brain area whose anatomical structure evolves substantially still in adult animals by establishing new synaptic connections and removing existing ones. We present a computational model for this process and employ it to interpret recent experimental results. By comparing the results of our model with those of a random control model we identify various experimental observations that lend strong support to the notion that the network of the olfactory bulb comprises learned, odor-specific subnetworks. Moreover, our model explains the recent observation that the learning of odors does not always improve their discriminability and provides testable predictions for the recovery of odor response after repeated odor exposure and for when the learning of new odors interferes with retaining the memory of familiar odors.