bluuebunny/crossref_metadata_2025 huggingface dataset:
Integration of Motivational Interviewing Within Prelicensure Nursing Programs
Authors: Badowski Donna , Rossler Kelly L. , Reiland Nanci , Gill Gembala Letitia (Tish)
Published: October 2021

Background:

Vital to the nurse-patient partnership is the use of active listening and a clear understanding of the patient's health care goals. Motivational Interviewing is an evidence-based, patient-centered communication technique that assists patients in self-identifying and committing to health behavior change.

Purpose:

This study explored whether, where, and how Motivational Interviewing is integrated into current prelicensure nursing curricula.

Methods:

An exploratory, descriptive study incorporated a researcher-developed survey.

Results:

Participants (N = 112) represented 5 types of prelicensure nursing programs from across the United States. Forty-one participants reported using Motivational Interviewing within their program with accreditation being the primary rationale. Seventy-one participants reported not integrating Motivational Interviewing within their program with lack of knowledge being the primary rationale.

Conclusion:

Further research on optimizing the integration of Motivational Interviewing educational content and practice into all levels and specialty areas of nursing education would help to identify best practices.
The 100 Most-Cited Articles in Liposuction
Authors: Reddy Rohin K. , Dutt Atul , Charles Walton N. , Hoyos Alfredo , Khajuria Ankur
Published: October 2021

Background

Liposuction is one of the most common cosmetic surgical procedures performed worldwide. Despite previous citation analyses in plastic surgery, the most-cited works in liposuction have not yet been qualitatively or quantitatively appraised. We hypothesized that use of validated outcome measures and levels of evidence would be low among these articles. Thus, we performed a bibliometric analysis aiming to comprehensively review the most-cited liposuction literature, evaluating characteristics and quality of the top 100 articles.

Methods

The 100 most-cited articles in liposuction were identified on Web of Science, across all available journals and years (1950–2020). Study details, including the citation count, main subject, and outcome measures, were extracted from each article by 2 independent reviewers. The level of evidence of each study was also assessed.

Results

The 100 most-cited articles in liposuction were cited by a total of 4809 articles. Citations per article ranged from 602 to 45 (mean, 92). Most articles were level of evidence 4 (n = 33) or 5 (n = 35), representative of the large number of case series, expert-opinion articles, and narrative reviews. Ten articles achieved level of evidence 3, 22 articles achieved level of evidence 2, and none reached level 1. The main subject was operative technique in 63 articles, followed by outcomes in 32 articles. Five articles assessed the metabolic effects of liposuction. Only 1 article used a validated objective cosmetic outcome measure, and none used validated patient-reported outcome measures.

Conclusions

This analysis provides an overview of the top cited liposuction literature. Overall, level of evidence was low, and no articles achieved the highest level of evidence. Improving the quality of literature requires prioritization of better-designed studies and incorporation of validated outcome measures, which will increase patient satisfaction and ensure provision of excellent, reproducible clinical care.
Correction of Midface Deficiency in Patient With Crouzon Syndrome by Orthognathic Surgery and Patient Specific Facial Implant: Case Report
Authors: Ha Sung-Ho , Lee HyunJong , Choi Jin-Young
Published: October 2021

Crouzon syndrome, also known as craniofacial dysostosis, is an autosomal dominant inherited disease characterized by early cranial fusion and consequential craniofacial malformations. In patients with Crouzon syndrome, the growth of the midface is affected due to early fusion of the cranial base, which results in exophthalmos, ocular ptosis, midface deficiency, and maxillary retrognathism. Frontofacial advancement using Le Fort III osteotomy is the conventional method for treating patients with Crouzon syndrome. However, this procedure has drawbacks such as extensive operation field and high possibility of serious complications (eg, meningitis). For patients with mild symptoms, facial esthetics and proper occlusion can be promoted through conventional orthognathic surgery, but midface deficiency cannot be completely resolved. Thus, in this case report, midface augmentation was performed for a patient with Crouzon syndrome by undergoing conventional orthognathic surgery, along with patient-specific implants made using a 3D virtual technique. Implants were 3D printed using polyetherketoneketone and simultaneously implanted during the orthognathic surgery. After the surgery, not only were the patient's occlusion and facial esthetics improved, but also exophthalmos and ocular ptosis were reduced by the midfacial augmentation effect of patient-specific implants placed in the midface. Since the implants were made exactly as what surgeons have intended through computer-aided design (CAD)/computer-aided manufacturing (CAM) and 3D printing techniques, problems such as under-/over-correction were avoided. In addition, the possibility of implant malpositioning was minimized using surgical stents as implants were passively fitted on the patient's bone surface. This case verified that the application of 3D technology to the field of oral and maxillofacial surgery can reduce the invasiveness of surgery and improve the accuracy of the operation. Therefore, by using cutting-edge technologies, the field of oral and maxillofacial surgery is expected to be developed further in the near future.
Comparison of Blowout Fracture Sites Observed in Young and Elderly East Asians
Authors: Hong Suji , Choi Kwang-Eon , Kim Joohyun , Baek Sehyun
Published: October 2021

The purpose of this study was to investigate the distribution of blowout fracture sites among age groups and compare clinical factors that can affect the fracture site. The authors reviewed 330 cases of blowout fracture surgeries and included 226 eyes of 226 patients aged between 20 and 29 years and between 50 and 59 years who underwent blowout fracture reconstruction between January 2017 and December 2020, in the Department of Ophthalmology at Korea University Hospital.

Medical records including patient demography, trauma etiology, and preoperative computed tomography image were evaluated. Ethmoidal cell septa and fracture site position were compared between the 2 age groups. The causes of injury were categorized into 3 groups: focal trauma, gross trauma, and other causes. Orbital floor fracture was the most common type (40.00%) in the young group, followed by medial wall fracture (25.33%). in contrast, medial wall fracture accounted for the largest proportion (42.11%) in the older group, and orbital floor fracture accounted for only 26.67%. The major cause of blowout fracture in young patients was focal trauma, whereas gross trauma was the most common cause in the older group. The number of ethmoidal cells was 4.19 ± 0.831 (2–6) in the young group and 3.91 ± 1.022 (2–6) in the old group (P 
< 0.05). Distribution of blowout fracture site differed between age groups, and these differences can be explained by cause of injury and number of ethmoidal cells.
Extravasation and outcomes in computed tomography and angiography in patients with pelvic fractures requiring transcatheter arterial embolization: A single-center observational study
Authors: Nakajima Kento , Yamaguchi Keishi , Abe Takeru , Taniguchi Hayato , Mizukami Saori , Sekikawa Zenjiro , Takeuchi Ichiro
Published: October 2021

BACKGROUND

Extravasation on contrast-enhanced computed tomography (CECT) is a helpful indicator of the need for transcatheter arterial embolization (TAE) for pelvic fractures. However, previous reports were inconsistent on cases in which angiography is necessary, even though there is no extravasation on computed tomography. This study aimed to describe and analyze the contradictory findings in cases where extravasation is observed on angiography but not on CECT, to contribute to improved management of patients with pelvic fractures.

METHODS

This was a retrospective single-center study. Patients with pelvic fractures who underwent CECT and TAE between 2014 and 2020 were included. We classified the patients into three groups: CECT and angiography with extravasation (CT+Angio+), CECT with no extravasation and angiography with extravasation (CT−Angio+), and CECT with extravasation and angiography without extravasation (CT+Angio−).

RESULTS

A total of 113 patients were included in the study: the CT+Angio+ group had 54 patients, CT−Angio+ group, 47; and CT+Angio− group, 12. The CT−Angio+ group had a significantly longer time from arrival to CECT than the CT+Angio+ group (27 minutes vs. 23 minutes, p < 0.05). The CT−Angio+ group had significantly more blood transfusions (fresh frozen plasma, platelets) within 24 hours than the CT+Angio− group did (p < 0.05), and ventilator management days (p < 0.05) and intensive care unit stays (p < 0.05) were significantly longer.

CONCLUSION

There was no significant difference in outcomes among the three groups. There was no difference in severity, transfusion volume, or mortality in patients with pelvic fractures needing TAE, classified as CT−Angio+, compared with that of CT+Angio+ patients. Even in the absence of extravasation in the pelvic region on CECT, angiography or TAE may still be necessary.

LEVEL OF EVIDENCE

Therapeutic/Care Management, Level IV.
Proposed Pathway for the Utilization of Pediatric Ambulatory EEG
Authors: Borlot Felippe , Kozlik Silvia , Alfaro Leanne , Payne Eric T. , Ho Alice W. , Appendino Juan P. , Scantlebury Morris H. , Jacobs Julia
Published: October 2021

Purpose:

The clinical utility of pediatric ambulatory-EEG (A-EEG) has been studied for decades, but limited information exists regarding which variables influence its utility. The authors aimed to evaluate clinical/EEG variables that may influence A-EEG yields and to develop a pathway for A-EEG utilization in children.

Methods:

Single-center retrospective review of A-EEGs performed from July 2019 to January 2021 in a tertiary referral center. The primary outcome was whether the A-EEG test successfully answered the referring physician's clinical question or influenced therapy. When it did, the A-EEG test was deemed useful. Clinical and EEG variables were assessed for their ability to predict utility. Further, the literature review generated 10 relevant prior studies whose details were used to generate a pathway for A-EEG utilization in children.

Results:

One hundred forty-two A-EEG studies were included (mean age 8.8 years, 48% male patients, mean A-EEG duration 33.5 hours). Overall, A-EEG was considered useful in 106 children (75%) but heavily influenced by A-EEG indication. Specifically, it was deemed useful for 94% of patients evaluated for electrical status epilepticus in slow-wave sleep, 92% of those evaluated for interictal/ictal burden, and 63% of those undergoing spell classification. The test indication (P < 0.001), a diagnosis of epilepsy (P = 0.02), and an abnormal routine EEG (P = 0.04) were associated with A-EEG test utility, although the multivariate analysis confirmed the test indication as the only independent outcome predictor of A-EEG.

Conclusions:

Pediatric A-EEG is extremely useful for evaluating electrical status epilepticus in slow-wave sleep and interictal/ictal burden and is often helpful for spell classification. Among all clinical and EEG variables analyzed, the test indication was the only independent outcome predictor of obtaining a helpful A-EEG.
The number of Follicle Stem Cells in a Drosophila ovariole
Authors: Kalderon Daniel , Melamed David , Reilein Amy
Published: October 2021

A paper by Reilein et al (2017) presented several fundamental new insights into the behavior of adult Follicle Stem Cells (FSCs) in the Drosophila ovary, including evidence that each ovariole hosts a large number of FSCs (14-16) maintained by population asymmetry (Reilein et al., 2017), rather than just two FSCs, dividing with largely individually asymmetric outcomes, as originally proposed (Margolis and Spradling, 1995; Nystul and Spradling, 2007). Fadiga and Nystul (2019) contest some of these conclusions on the basis of their repetition of a multicolor lineage strategy used by Reilein et al (2017) and repetition of earlier single-color lineage analysis. Here we outline a number of shortcomings in the execution and interpretation of those experiments that, in our opinion, undermine their conclusions. The central issue of general relevance concerns the importance of comprehensively analyzing all stem cell lineages, independent of any pre-conceptions, in order to identify all constituents and capture heterogeneous behaviors.
Boosting of the SARS-CoV-2-specific immune response after vaccination with single-dose Sputnik Light vaccine
Authors: Komissarov Alexey A. , Dolzhikova Inna V. , Efimov Grigory A. , Logunov Denis Y. , Mityaeva Olga , Molodtsov Ivan A. , Naigovzina Nelli B. , Peshkova Iuliia O. , Shcheblyakov Dmitry V. , Volchkov Pavel , Vasilieva Elena
Published: October 2021

Despite the measures taken worldwide, COVID-19 pandemic still progresses. While efficient antiviral drugs are not yet widely available, vaccination is the best option to control the infection rate. Although this option is obvious in case of COVID-19–naïve individuals, it is still unclear when individuals who have recovered from a previous SARS-CoV-2 infection should be vaccinated and whether the vaccination raises immune responses against the coronavirus and its novel variants. Here we measured the dynamics of the antibody and T-cell responses, as well as virus neutralizing activity (VNA) in serum against two SARS-CoV-2 variants, B.1.1.1 and B.1.617.2, among 84 individuals with different COVID-19 status who were vaccinated with Sputnik Light vaccine. We showed that vaccination of individuals previously exposed to the virus considerably boosts the existing immune response. In these individuals, RBD-specific IgG titers and VNA in serum were already elevated on the 7th day after vaccination, while COVID-19–naïve individuals developed the antibody response and VNA mainly 21 days post–vaccination. Additionally, we found a strong correlation between RBD-specific IgG titers and VNA in serum, and according to these data vaccination may be recommended if the RBD-specific IgG titers drop to 142.7 BAU/mL or below. In summary, the results of the study demonstrate that vaccination is beneficial both for COVID-19–naïve and recovered individuals, especially since it raises serum VNA against the B.1.617.2 variant – one of four the SARS-CoV-2 variants of concern.
EEG microstate dynamics indicate a U-shaped path to propofol-induced loss of consciousness
Authors: Artoni Fiorenzo , Maillard Julien , Britz Juliane , Seeber Martin , Lysakowski Christopher , Bréchet Lucie , Tramèr Martin R. , Michel Christoph M.
Published: October 2021

It is commonly believed that the stream of consciousness is not continuous but parsed into transient brain states manifesting themselves as discrete spatiotemporal patterns of global neuronal activity. Electroencephalographical (EEG) microstates are proposed as the neurophysiological correlates of these transiently stable brain states that last for fractions of seconds. To further understand the link between EEG microstate dynamics and consciousness, we continuously recorded high-density EEG in 23 surgical patients from their awake state to unconsciousness, induced by step-wise increasing concentrations of the intravenous anesthetic propofol. Besides the conventional parameters of microstate dynamics, we introduce a new method that estimates the complexity of microstate sequences. The brain activity under the surgical anesthesia showed a decreased sequence complexity of the stereotypical microstates, which became sparser and longer-lasting. However, we observed an initial increase in microstates’ temporal dynamics and complexity with increasing depth of sedation leading to a distinctive “U-shape” that may be linked to the paradoxical excitation induced by moderate levels of propofol. Our results support the idea that the brain is in a metastable state under normal conditions, balancing between order and chaos in order to flexibly switch from one state to another. The temporal dynamics of EEG microstates indicate changes of this critical balance between stability and transition that lead to altered states of consciousness.

Highlights

EEG microstates capture discrete spatiotemporal patterns of global neuronal activity

We studied their temporal dynamics in relation to different states of consciousness

We introduce a new method to estimate the complexity of microstates sequences

With moderate sedation complexity increases then decreases with full sedation

Complexity of microstate sequences is sensitive to altered states of consciousness
Patient-derived zebrafish xenograft models reveal ferroptosis as a fatal and druggable weakness in metastatic uveal melanoma
Authors: Groenewoud Arwin , Yin Jie , Gelmi Maria Chiara , Alsafadi Samar , Nemati Fariba , Decaudin Didier , Roman-Roman Sergio , Kalirai Helen , Coupland Sarah E. , Jochemsen Aart G. , Jager Martine J. , Snaar-Jagalska Ewa
Published: October 2021

Uveal melanoma (UM) is the most common intraocular melanoma, derived from transformed melanocytes of the uvea. Although treatment of primary UM is usually successful, there is a high risk (up to 50%) of liver metastasis with negligible long-term survival. There are currently no reproducible patient-derived animal models that faithfully recapitulate the latter stages of metastatic dissemination of UM, hindering the discovery of curative treatments. To overcome this problem and to accelerate the development of new metastatic UM treatments, we developed a patient-derived zebrafish xenograft (zf-PDX) model, using spheroid cultures generated from metastatic and primary UM tissues. Engrafted UM cells derived from these spheroid cultures give rise to metastatic lesions and recapitulate the molecular features of UMs and their potential drug sensitivity. Importantly, harnessing this versatile model, we reveal a high sensitivity of circulating UM cells to ferroptosis induction in vivo by Erastin and RSL3. Our findings are further corroborated by supportive analysis of patient data implicating ferroptosis as a new, and druggable, target for the treatment of metastatic UM patients, specifically in those with BAP1 loss in the tumor.
Phototroph-heterotroph interactions during growth and long-term starvation across Prochlorococcus and Alteromonas diversity
Authors: Weissberg Osnat , Aharonovich Dikla , Sher Daniel
Published: October 2021

Microbial interactions such as those between phytoplankton and bacteria been studied intensively using specific model organisms, due to their potential impact on ecosystems and biogeochemistry. Yet, to what extent interactions differ between closely related organisms, or how these interactions change over time or culture conditions, remains unclear. Here, we characterize the interactions between five strains each of two globally abundant marine microorganisms, Prochlorococcus (a phototroph) and Alteromonas (a heterotroph), from the first encounter between individual strains and over more than a year of repeated cycles of exponential growth and long-term nitrogen starvation. Prochlorococcus-Alteromonas interactions had little effect on traditional growth parameters such as Prochlorococcus growth rate, maximal fluorescence or lag phase, affecting primarily the dynamics of culture decline, which we interpret as representing cell mortality and lysis. The shape of the Prochlorococcus decline curve and the carrying capacity of the co-cultures were determined by the phototroph and not the heterotroph strains involved. Comparing various mathematical models of culture mortality suggests that Prochlorococcus death rate increases over time in mono-cultures but decreases in co-cultures, with cells potentially becoming more resistant to stress. Our results demonstrate intra-species differences in ecologically-relevant co-culture outcomes. These include the recycling efficiency of N and whether the interactions are mutually synergistic or competitive. They also highlight the information-rich growth and death curves as a useful readout of the interaction phenotype.

Significance Statement

Interactions between phytoplankton and marine bacteria impact global ecosystems and biogeochemistry. Here, we explore how intra-species variability affects the interactions between Prochlorococcus, a globally abundant photosynthetic cyanobacetrium and Alteromonas, a heterotrophic bacterium that lives off and recycles organic matter. Under nitrogen starvation, Prochlorococcus growing alone increasingly accumulate damage and die, whereas in co-culture with Alteromonas they become increasingly resilient. The specific Prochlorococcus strain had a much larger effect on co-culture behavior than the Alteromonas strain, determining whether the interactions are mutually synergistic or potentially competitive. These results show how ecologically relevant outcomes of interactions may vary between closely related microorganisms, and highlight growth and death curves from laboratory (co)-cultures as information-rich views of microbial growth and death.
Different mycorrhizal nutrient acquisition strategies shape tree species competition and coexistence dynamics
Authors: Van Nuland Michael E. , Ke Po-Ju , Wan Joe , Peay Kabir G.
Published: October 2021

Mycorrhizal fungi with different nutrient acquisition strategies influence the functional separation among plant species. This might drive resource competition dynamics that cumulatively impact tree species coexistence, but few manipulative experiments have directly tested this. Combining surveys and experiments in a modern coexistence theory framework, we tested how variation in mycorrhizal strategies and nutrient conditions affect competitive outcomes between co-occurring ectomycorrhizal (EM)and arbuscular mycorrhizal (AM) tree species. The dependency on EM symbioses increased with latitude and nitrogen (N) limitation, matching global trends. Host-specific soil microbiome conditioning and N fertilization combined to qualitatively affect coexistence outcomes. Lower N conditions favored EM over AM trees, but N fertilization reversed this outcome for southern species, consistent with regional-scale forest mycorrhizal transitions. As the magnitude and outcome of microbially-mediated competition depends on mycorrhizal differentiation and soil nutrient availability, this strongly supports the importance of mycorrhizal symbioses in driving large-scale biogeographic patterns of tree species.
KIBRA-PKCγ signaling pathway modulates memory performance in mice and humans
Authors: Tian Mengnan , Chen Qiang , Graves Austin R. , Goldschmidt Hana L. , Johnson Richard C. , Weinberger Daniel R. , Huganir Richard L.
Published: October 2021

Human memory is a polygenic cognitive trait that is fundamental to individual competence. Genome-wide association studies (GWAS) have identified KIBRA as a novel gene associated with human memory performance. KIBRA interacts with AMPA receptors (AMPARs) and proteins essential for synaptic plasticity. The deletion of Kibra in mice impairs synaptic plasticity and learning and memory. However, the molecular basis through which KIBRA regulates dynamic AMPAR trafficking underlying synaptic plasticity is still unknown. Here we report that KIBRA interacts with the neuronal specific kinase PKCγ to modulate AMPAR trafficking upon learning, and KIBRA-PKCƔ signaling pathway also associates with human memory performance. We find PKCƔ is an essential kinase that phosphorylates AMPARs upon learning, and the loss of KIBRA in mouse brain impedes PKCƔ-AMPAR interaction. Activation of PKCƔ enables KIBRA to recruit phosphorylated AMPARs to the synapse to promote LTP and learning. We further performed transcriptomic and genetic analyses in human postmortem brain samples, and behavioral and fMRI evaluations in living human subjects, to demonstrate the genetic interactions between KIBRA and PRKCG on memory performance and memory associated physiological engagement of the hippocampal memory system. Overall, our results support that the KIBRA-PKCƔ signaling pathway is crucial for modulating memory performance in mice and humans.
Signaling from the RNA sensor RIG-I is regulated by ufmylation
Authors: Snider Daltry L. , Park Moonhee , Murphy Kristen A. , Beachboard Dia C. , Horner Stacy M.
Published: October 2021

The RNA binding protein RIG-I is a key initiator of the antiviral innate immune response. The signaling that mediates the antiviral response downstream of RIG-I is transduced through the adaptor protein MAVS and results in the induction of type I and III interferons (IFN). This signal transduction occurs at endoplasmic reticulum (ER)-mitochondrial contact sites, to which RIG-I and other signaling proteins are recruited following their activation. RIG-I signaling is highly regulated to prevent aberrant activation of this pathway and dysregulated induction of IFN. Previously, we identified UFL1, the E3 ligase of the ubiquitin-like modifier conjugation system called ufmylation, UFL1, as one of the proteins recruited to membranes at ER-mitochondrial contact sites in response to RIG-I activation. Here, we show that UFL1, as well as the process of ufmylation, promote IFN induction in response to RIG-I activation. We find that following RNA virus infection, UFL1 is recruited to the membrane targeting protein 14-3-3ε, and that this complex is then recruited to activated RIG-I to promote downstream innate immune signaling. Importantly, we found that 14-3-3ε has an increase in UFM1-conjugation following RIG-I activation. Additionally, loss of cellular ufmylation prevents the interaction of 14-3-3ε with RIG-I, which abrogates the interaction of RIG-I with MAVS and thus downstream signal transduction that induces IFN. Our results define ufmylation as an integral regulatory component of the RIG-I signaling pathway and as a post-translational control for IFN induction.

Significance

The viral RNA sensor RIG-I initiates the antiviral innate immune response by activating a signaling cascade that induces interferon. Activation of the RIG-I signaling pathway is highly regulated to quickly mount a protective immune response while preventing dysregulation that can lead to excessive inflammation or autoimmune disorders. Here, we characterize one such mechanism of regulation. We describe that UFL1, an E3 ligase for the ubiquitin-like modifier conjugation system called ufmylation, is important to promote RIG-I signaling. Using molecular approaches, we show that ufmylation promotes RIG-I interaction with the membrane targeting protein 14-3-3ε. As such, ufmylation positively regulates RIG-I recruitment to its signaling adaptor proteins MAVS for induction of interferon in response to RNA virus infection.
Long-Term Inactivation of Sodium Channels as a Mechanism of Adaptation in CA1 Pyramidal Neurons
Authors: Upchurch Carol , Combe Crescent , Knowlton Christopher , Rousseau Valery , Gasparini Sonia , Canavier Carmen C.
Published: October 2021

Many hippocampal CA1 pyramidal cells function as place cells, increasing their firing rate when a specific place field is traversed. The dependence of CA1 place cell firing on position within the place field is asymmetric. We investigated the source of this asymmetry by injecting triangular depolarizing current ramps to approximate the spatially-tuned, temporally-diffuse depolarizing synaptic input received by these neurons while traversing a place field. Ramps were applied to CA1 pyramidal neurons from male rats in vitro (slice electrophysiology) and in silico (multi-compartmental NEURON model). Under control conditions, CA1 neurons fired more action potentials at higher frequencies on the up-ramp versus the down-ramp. This effect was more pronounced for dendritic compared to somatic ramps. We incorporated a four-state Markov scheme for NaV1.6 channels into our model and calibrated the spatial dependence of long-term inactivation according to the literature; this spatial dependence was sufficient to explain the difference in dendritic versus somatic ramps. Long-term inactivation reduced the firing frequency by decreasing open-state occupancy, and reduced spike amplitude during trains by decreasing occupancy in closed states, which comprise the available pool. PKC activator phorbol-dibutyrate, known to reduce NaV long-term inactivation, removed spike amplitude attenuation in vitro more visibly in dendrites and greatly reduced adaptation, consistent with our hypothesized mechanism. Intracellular application of a peptide inducing long-term NaV inactivation elicited spike amplitude attenuation during spike trains in the soma and greatly enhanced adaptation. Our synergistic experimental/computational approach shows that long-term inactivation of NaV1.6 is a key mechanism of adaptation in CA1 pyramidal cells.

Significance statement

The hippocampus plays an important role in certain types of memory, in part through context-specific firing of “place cells”; these cells were first identified in rodents as being particularly active when an animal is in a specific location in an environment, called the place field of that neuron. In this in vitro/in silico study, we found that long-term inactivation of sodium channels causes adaptation in the firing rate that could potentially skew the firing of CA1 hippocampal pyramidal neurons earlier within a place field. A computational model of the sodium channel revealed differential regulation of spike frequency and amplitude by long-term inactivation, which may be a general mechanism for spike frequency adaptation in the central nervous system.
Deep Heterogeneous Dilation of LSTM for Transient-phase Gesture Prediction through High-density Electromyography: Towards Application in Neurorobotics
Authors: Sun Tianyun , Hu Qin , Libby Jacqueline , Atashzar S. Farokh
Published: October 2021

Deep networks have been recently proposed to estimate motor intention using conventional bipolar surface electromyography (sEMG) signals for myoelectric control of neurorobots. In this regard, Deepnets are generally challenged by long training times (affecting practicality and calibration), complex model architectures (affecting the predictability of the outcomes), and a large number of trainable parameters (increasing the need for big data). Capitalizing on our recent work on homogeneous temporal dilation in a Recurrent Neural Network (RNN) model, this paper proposes, for the first time, heterogeneous temporal dilation in an LSTM model and applies that to high-density surface electromyography (HD-sEMG), allowing for the decoding of dynamic temporal dependencies with tunable temporal foci. In this paper, a 128-channel HD-sEMG signal space is considered due to the potential for enhancing the spatiotemporal resolution of human-robot interfaces. Accordingly, this paper addresses a challenging motor intention decoding problem of neurorobots, namely, transient intention identification. Our approach uses only the dynamic and transient phase of gesture movements when the signals are not stabilized or plateaued, which can significantly enhance the temporal resolution of human-robot interfaces. This would eventually enhance seamless real-time implementations. Additionally, this paper introduces the concept of “dilation foci” to modulate the modeling of temporal variation in transient phases. In this work a high number (e.g., 65) of gestures is included, which adds to the complexity and significance of the understudied problem. Our results show state-of-the-art performance for gesture prediction in terms of accuracy, training time, and model convergence.
Descriptive analysis of social determinant of mental health factors in an ethnically diverse Black adult population
Authors: Pederson Aderonke Bamgbose , Hawkins Devan , Lartey Lynette
Published: October 2021

Background

Black adults are often treated as a homogeneous group in research and health care despite the diversity within the Black population across ethnicity. This study considers ethnicity in assessing the heterogeneity among Black adults across multiple social determinants of mental health. Understanding the diversity within the Black population will help close the gap in mental health disparities by offering a more streamlined approach to meeting unmet mental health needs.

Methods

A cross-sectional descriptive study and analysis was conducted among Black adults in the United States (n = 269, ages 18-65) from diverse ethnic backgrounds (African-Americans, African immigrants, Afro-Caribbean immigrants). We calculated mean differences according to ethnicity, citizenship status, age group, and gender in the areas of medical mistrust, use of mental health services, depression symptom severity, mental health knowledge and stigma behavior.

Results

African Americans with moderate to severe depression symptoms had greater stigma behavior (mean = 12.2, SD = 3.2), than African Americans who screened in the minimal to mild depression range (mean = 13.1, SD = 3.5). Black immigrants across the spectrum of depression scores had greater stigma than African Americans (p = 0.037). Participants who identified as male had a prevalence of mild depression (5-9) that was 1.7 times higher than those who identified as female. Whereas, those who identified as female had a prevalence that was 1.2 times higher for moderate to severe depression (10-19) and 4.7 times higher for severe depression (20-27) compared to males (p = 0.021). Non-United States citizens reported higher medical mistrust (mean value difference = 0.16) compared to United States citizens (p = 0.011). We found statistically significant differences in depression symptom severity based on gender, prevalence of depression, medical mistrust and stigma behavior across demographic factors within the sample.

Conclusion

This study shows key variations across social determinant of mental health factors within the Black adult population. There is a need to better understand the heterogeneity within the Black population in order to improve the effectiveness of programs that seek to reduce mental health disparities.
Structure Insight into Photosystem I Octamer from Cyanobacteria
Authors: Chen Ming , He Yujie , Liu Dongyang , Tian Lijin , Xu Pengqi , Liu Xuan , Pan Yihang , He Jun , Zhang Ying
Published: October 2021

Diversity of photosystem oligomers is essential to understand how photosynthetic organisms adopted to light conditions. Given by the structural and physiological significance, the assemblies of PSI supercomplex is of great interest in both chloroplast and cyanobacteria recently. In this study, two novel photosystem I supercomplexes were isolated for the first time from the low light incubated culture of filamentous cyanobacterium Anabaena sp. PCC 7120. These complexes were defined as PSI hexamers and octamers through biochemical and biophysical characterization. Their 77K emission spectra indicated that the red forms of chlorophylls seemed not to be affected during oligomerization. By cryo-EM single particle analysis, a near-atomic (7.0 Å) resolution structure of PSI octamer was resolved, and the molecular assemblies of stable PSI octamer was revealed.
Sequence dependencies and mutation rates of localized mutational processes in cancer
Authors: Poulsgaard Gustav Alexander , Sørensen Simon Grund , Juul Randi Istrup , Nielsen Morten Muhlig , Pedersen Jakob Skou
Published: October 2021

Background

Cancer mutations accumulate through replication errors and DNA damage coupled with incomplete repair. Individual mutational processes often show strong sequence and regional preferences. As a result, some sequence contexts mutate at much higher rates than others. Mutational hotspots, with recurrent mutations across cancer samples, represent genomic positions with elevated mutation rates, often caused by highly localized mutational processes.

Results

We analyze the mutation rates of all 11-mer genomic sequence contexts using the PCAWG set of 2,583 pan-cancer whole genomes. We further associate individual mutations and contexts to mutational signatures and estimate their relative mutation rates. We show that hotspots generally identify highly mutable sequence contexts. Using these, we show that some mutational signatures are enriched in hotspot sequence contexts, corresponding to well-defined sequence preferences for the underlying localized mutational processes. This includes signature 17b (of unknown etiology) and signatures 62 (POLE), 7a (UV), and 72 (linked to lymphomas). In some cases, the mutation rate increases further when focusing on certain genomic regions, such as signature 62 in poised promoters, where the mutation is increased several thousand folds over the overall data set average.

Conclusion

We summarize our findings in a catalog of localized mutational processes, their sequence preferences, and their estimated mutation rates.
Brain macrophages acquire distinct transcriptomes prior to demyelination in multiple sclerosis
Authors: Miedema Anneke , Gerrits Emma , Brouwer Nieske , Jiang Qiong , Kracht Laura , Meijer Michel , Nutma Erik , Peferoen-Baert Regina , Pijnacker Anna T.E. , Wesseling Evelyn M. , Wijering Marion H.C. , Gabius Hans-Joachim , Amor Sandra , Eggen Bart J.L. , Kooistra Susanne M.
Published: October 2021

Multiple sclerosis (MS) is a disease of the central nervous system (CNS) that is characterized by inflammation and focal areas of demyelination, ultimately resulting in axonal degradation and neuronal loss. Several lines of evidence point towards a role for microglia and other brain macrophages in disease initiation and progression, but exactly how lesion formation is triggered is currently unknown. Here, we characterized early changes in MS brain tissue through transcriptomic analysis of normal appearing white matter (NAWM). We found that NAWM was characterized by enriched expression of genes associated with inflammation and cellular stress derived from brain macrophages. Single cell RNA sequencing confirmed an early stress response in brain macrophages in NAWM and identified specific macrophage subsets that associate with different stages of demyelinating lesions. These early changes associated with lesion development in MS brain tissue may provide therapeutic targets to limit lesion progression and demyelination.
Long-term stability of single neuron activity in the motor system
Authors: Jensen Kristopher T. , Harpaz Naama Kadmon , Dhawale Ashesh K. , Wolff Steffen B. E. , Ölveczky Bence P.
Published: October 2021

How an established behavior is retained and stably produced by a nervous system in constant flux remains a mystery. One possible solution is to fix the activity patterns of single neurons in the relevant circuits. Alternatively, activity in single cells could drift over time provided that the population dynamics are constrained to produce stable behavior. To arbitrate between these possibilities, we recorded single unit activity in motor cortex and striatum continuously for several weeks as rats performed stereotyped motor behaviors – both learned and innate. We found long-term stability in single neuron activity patterns across both brain regions. A small amount of drift in neural activity, observed over weeks of recording, could be explained by concomitant changes in task-irrelevant behavioral output. These results suggest that stereotyped behaviors are generated by stable single neuron activity patterns.
Neurons in human pre-supplementary motor area encode key computations for value-based choice
Authors: Aquino Tomas G. , Cockburn Jeffrey , Mamelak Adam N. , Rutishauser Ueli , O’Doherty John P.
Published: October 2021

Adaptive behavior in real-world environments demands that choices integrate over several variables, including the novelty of the options under consideration, their expected value, and uncertainty in value estimation. We recorded neurons from the human pre-supplementary motor area (preSMA), ventromedial prefrontal cortex (vmPFC) and dorsal anterior cingulate to probe how integration over decision variables occurs during decision-making. In contrast to the other areas, preSMA neurons not only represented separate pre-decision variables for each choice option, but also encoded an integrated utility signal and, subsequently, the decision itself. Conversely, post-decision related encoding of variables for the chosen option was more widely distributed and especially prominent in vmPFC. Our findings position the human preSMA as central to the implementation of value-based decisions.
Dendritic cell ICAM-1 strengthens immune synapses but is dispensable for effector and memory responses
Authors: Sapoznikov Anita , Kozlovski Stav , Feigelson Sara W , Davidzohn Natalia , Wigoda Noa , Feldmesser Ester , Petrovich-Kopitman Ekaterina , Grafen Anika , Biton Moshe , Alon Ronen
Published: October 2021

Lymphocyte priming in lymph nodes (LNs) depends on the formation of functional TCR specific immune synapses (ISs) with antigen (Ag) presenting dendritic cells. The high affinity LFA-1 ligand ICAM-1 has been implicated in different ISs studiedin vitro. The in vivo roles of DC ICAM-1 in Ag stimulated T cell differentiation have been unclear. In newly generated DC conditional ICAM-1 knockout mice, we report that under Th1 polarizing conditions, ICAM-1 deficient DCs could not engage in stable conjugates with newly generated CD8 blasts. Nevertheless, these DCs triggered normal lymphocyte priming, proliferation and differentiation into functional cytotoxic T cells (CTLs) and central memory lymphocytes (Tcm) in both vaccinated and virus infected skin. Single cell RNAseq analysis confirmed that Tcm were normally generated in these mice and gave rise to normal T effectors during a recall skin response. Our results suggest that although CD8 T cell blasts tightly bind DC-ICAM-1, strongly adhesive DC-T ISs are not necessary for functional TCR dependent DC mediated CD8 T cell proliferation and differentiation into productive effector and memory lymphocytes.

Sapoznikov et al generated a new genetic murine model deficient in dendritic cell expression of the key adhesion molecule ICAM-1 and found that CD8 lymphocytes do not require strong adhesion to dendritic cells for antigen-dependent differentiation into effector and memory T cells.
Phylogenetic analysis and in silico studies link spike Q675H mutation to SARS-CoV-2 adaptive evolution
Authors: Anna Bertelli , Pasqualina D’Ursi , Giovanni Campisi , Serena Messali , Maria Milanesi , Marta Giovanetti , Massimo Ciccozzi , Francesca Caccuri , Arnaldo Caruso
Published: October 2021

Genotype screening was implemented in Italy and showed a significant prevalence of new SARS-CoV-2 mutants carrying Q675H mutation, near the furin cleavage site of spike protein. Currently, this mutation, which is expressed on different SARS-CoV-2 lineages circulating worldwide, has not been thoughtfully investigated. Therefore, we performed phylogenetic and biocomputational analysis to better understand SARS-CoV-2 Q675H mutants’ evolutionary relationships with other circulating lineages and Q675H function in its molecular context. Our studies reveal that Q675H spike mutation is the result of parallel evolution because it arose independently in separate evolutionary clades. In silico data show that the Q675H mutation gives rise to a hydrogen-bonds network in the spike polar region delimiting the conformational space of the highly flexible loop containing the furin cleavage site. This results in an optimized directionality of arginine residues involved in interaction of spike with the furin binding pocket, thus improving proteolytic exposure of the viral protein. Furin was found to have a greater affinity for Q675H than Q675 substrate conformations. As a consequence, Q675H mutation is likely to confer a fitness advantage to SARS-CoV-2 by promoting a more efficient viral entry. Interestingly, here we show an ongoing increase in the occurrence of Q675H spike mutation in the most common SARS-CoV-2 variants of concern (VOC). This finding highlights that, VOC are still evolving and start acquiring the Q675H mutation. At the same time, it suggests that our hypothesis of fitness advantage prompted by Q675H could be concrete.
Neural network models for spinal implementation of muscle synergies
Authors: Song Yunqing , Hirashima Masaya , Takei Tomohiko
Published: October 2021

Muscle synergies have been proposed as functional modules to simplify the complexity of body motor control; however, their neural implementation is still unclear. Converging evidence suggests that output projections of the spinal premotor interneurons (PreM-INs) underlie the formation of muscle synergies, but they exhibit a substantial variation across neurons and exclude standard models assuming a small number of unitary “modules” in the spinal cord. Here we compared neural network models for muscle synergies to seek a biologically plausible model that reconciles previous clinical and electrophysiological findings. We examined three neural network models: one with random connections (non-synergy model), one with a small number of spinal synergies (simple synergy model), and one with a large number of spinal neurons representing muscle synergies with a certain variation (population synergy model). We found that the simple and population synergy models emulate the robustness of muscle synergies against cortical stroke observed in human stroke patients. Furthermore, the size of the spinal variation of the population synergy matched well with the variation in spinal PreM-INs recorded in monkeys. These results suggest that a spinal population with moderate variation is a biologically plausible model for the neural implementation of muscle synergies.
Spindle - slow oscillation coupling correlates with memory performance and connectivity changes in a hippocampal network after sleep
Authors: Bastian Lisa , Samanta Anumita , de Paula Demetrius Ribeiro , Weber Frederik , Schoenfeld Robby , Dresler Martin , Genzel Lisa
Published: October 2021

After experiences are encoded, post-encoding reactivations during sleep have been proposed to mediate long-term memory consolidation. Spindle-slow oscillation coupling during NREM sleep is a candidate mechanism through which a hippocampal-cortical dialogue may strengthen a newly formed memory engram. Here, we investigated the role of fast spindle- and slow spindle-slow oscillation coupling in the consolidation of spatial memory in humans with a virtual water maze task involving allocentric and egocentric learning strategies. Furthermore, we analyzed how resting-state functional connectivity evolved across learning, consolidation, and retrieval of this task using a data-driven approach. Our results show task-related connectivity changes in the executive control network, the default mode network, and the hippocampal network at post-task rest. The hippocampal network could further be divided into two subnetworks of which only one showed modulation by sleep. Decreased functional connectivity in this subnetwork was associated with higher spindle-slow oscillation coupling power, which was also related to better memory performance at test. Overall, this study contributes to a more holistic understanding of the functional resting-state networks and the mechanisms during sleep associated to spatial memory consolidation.