bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of sleep restriction therapy for insomnia on sleep pressure and arousal: a randomized controlled mechanistic trial
Authors: Maurer Leonie F , Espie Colin A , Omlin Ximena , Emsley Richard , Kyle Simon D
Published: August 2021

Study Objectives

Sleep restriction therapy (SRT) effectively treats insomnia but mechanisms are poorly understood. Theoretical models suggest that potentiation of sleep pressure and reduction of arousal are key mechanisms of action. To our knowledge, this has never been directly tested. We designed a randomized controlled trial with embedded mechanistic measurement to investigate if SRT causally modifies multidimensional assessments of sleep pressure and arousal.

Methods

Participants aged 25–55 who met DSM-5 diagnostic criteria for insomnia disorder were randomized to four weeks of SRT or time in bed regularization (TBR), a control intervention that involves prescription of a regular but not reduced time in bed. Sleep pressure was assessed through daily diary appraisal of morning and evening sleepiness, weekly Epworth sleepiness scale (ESS) scores, psychomotor vigilance, and non-rapid eye movement (NREM) delta power (0.75–4.5 Hz) from ambulatory polysomnographic recordings. Arousal was assessed through daily diary appraisal of cognitive arousal, the pre-sleep arousal scale (PSAS), and NREM beta power (15–32 Hz). Outcomes were assessed at baseline (2-week period prior to randomization), during the intervention phase (1–4 weeks post-randomization), and at 12-week follow-up. We performed intention-to-treat analyses using linear mixed models. For continuous daily measures, the treatment period was split into early (weeks 1–2) and late (weeks 3–4) treatment.

Results

Fifty-six participants (39 females, mean age = 40.78 ± 9.08) were assigned to SRT (n = 27) or TBR (n = 29). The SRT group showed enhanced sleep pressure relative to TBR, reflected in (1) enhanced sleepiness in the evening during early (d = 1.17) and late treatment (d = 0.92), and in the morning during early treatment (d = 0.47); (2) higher daytime sleepiness on the ESS at weeks-1 and -2 (d = 0.54, d = 0.45); and (3) reduced psychomotor vigilance at week-1 (d = 0.34). The SRT group also showed reduced arousal relative to TBR, reflected in lower levels of daily-monitored cognitive arousal during early treatment (d = 0.53) and decreased PSAS total score at week-4 and week-12 (ds ≥ 0.39). Power spectral analysis of all night NREM sleep revealed an increase in relative, but not absolute, EEG delta power at week-1 and week-4 (ds ≥ 0.52) and a decrease of relative EEG beta power at week-4 (d = 0.11).

Conclusion

For the first time, we show that SRT increases sleep pressure and decreases arousal during acute implementation, providing support for mechanism-of-action.
Insomnia predicts treatment engagement and symptom change: a secondary analysis of a web-based CBT intervention for veterans with PTSD symptoms and hazardous alcohol use
Authors: Buckheit Katherine A , Nolan Jon , Possemato Kyle , Maisto Stephen , Rosenblum Andrew , Acosta Michelle , Marsch Lisa A
Published: August 2021

Posttraumatic Stress Disorder (PTSD) and hazardous drinking are highly comorbid, and often more severe than PTSD or hazardous drinking alone. Integrated, web-based interventions for PTSD/hazardous drinking may increase access to care, but have demonstrated equivocal results in reducing PTSD and hazardous drinking. One factor that may explain treatment engagement and symptom change is the presence of insomnia symptoms. The current study conducted secondary data analysis of a randomized controlled trial of an integrated web-based intervention for PTSD symptoms and hazardous drinking to examine insomnia symptoms as predictors of PTSD symptoms, alcohol use, and treatment engagement. In the parent study, 162 veterans in primary care reporting PTSD symptoms and hazardous drinking were randomized to receive either the intervention or treatment as usual. The current study examined insomnia among veterans who received the intervention (n = 81). Regression models tested baseline insomnia symptoms as predictors of treatment engagement, follow-up PTSD symptoms, and alcohol use. Hierarchical regression models tested change in insomnia during treatment as a predictor of follow-up PTSD symptoms and alcohol use. Results showed baseline insomnia predicted treatment engagement and follow-up drinking days, but not PTSD symptoms or heavy drinking days. Although overall change in insomnia was small, it predicted follow-up PTSD and heavy drinking days, but not drinking days. Results are consistent with previous research highlighting the importance of identifying and treating insomnia in the course of integrated treatment for PTSD/hazardous drinking. Future research should investigate how to best integrate insomnia, PTSD, and/or hazardous drinking interventions to maximize treatment engagement.
The central role of Italy in the spatial spread of USUTU virus in Europe
Authors: Zecchin B , Fusaro A , Milani A , Schivo A , Ravagnan S , Ormelli S , Mavian C , Michelutti A , Toniolo F , Barzon L , Monne I , Capelli G
Published: August 2021

USUTU virus (USUV) is an arbovirus maintained in the environment through a bird–mosquito enzootic cycle. Previous surveillance plans highlighted the endemicity of USUV in North-eastern Italy. In this work, we sequenced 138 new USUV full genomes from mosquito pools (Culex pipiens) and wild birds collected in North-eastern Italy and we investigated the evolutionary processes (phylogenetic analysis, selection pressure and evolutionary time-scale analysis) and spatial spread of USUV strains circulating in the European context and in Italy, with a particular focus on North-eastern Italy. Our results confirmed the circulation of viruses belonging to four different lineages in Italy (EU1, EU2, EU3 and EU4), with the newly sequenced viruses from the North-eastern regions, Veneto and Friuli Venezia Giulia, belonging to the EU2 lineage and clustering into two different sub-lineages, EU2-A and EU2-B. Specific mutations characterize each European lineage and geographic location seem to have shaped their phylogenetic structure. By investigating the spatial spread in Europe, we were able to show that Italy acted mainly as donor of USUV to neighbouring countries. At a national level, we identified two geographical clusters mainly circulating in Northern and North-western Italy, spreading both northward and southward. Our analyses provide important information on the spatial and evolutionary dynamics of USUTU virus that can help to improve surveillance plans and control strategies for this virus of increasing concern for human health.
Comparison of Chloroprocaine Versus Lidocaine With Epinephrine, Sodium Bicarbonate, and Fentanyl for Epidural Extension Anesthesia in Elective Cesarean Delivery: A Randomized, Triple-blind, Noninferiority Study
Authors: Sharawi N. , Bansal P. , Williams M. , Spencer H. , Mhyre J.M.
Published: August 2021

(Anesth Analg. 2021;132:666–675)

To facilitate intrapartum cesarean delivery anesthesia, patients with ongoing neuraxial labor analgesia receive a more potent local anesthetic through the epidural catheter to establish surgical anesthesia. When this technique is successful, patients can forego other neuraxial or general anesthesia for cesarean delivery. The study institution uses 2 anesthetic solutions for epidural extension anesthesia: 3% chloroprocaine (CP), or a mixture of 2% lidocaine, epinephrine, sodium bicarbonate, and fentanyl (LEBF). Since the mixture takes time to prepare, CP is used for unanticipated emergencies on labor and delivery. This randomized, triple-blind, noninferiority study aimed to compare the surgical anesthesia onset times of CP and LEBF for epidural extension anesthesia for cesarean delivery.
New Persistent Opioid Use After Acute Opioid Prescribing in Pregnancy: A Nationwide Analysis
Authors: Peahl A.F. , Morgan D.M. , Dalton V.K. , Zivin K. , Lai Y.L. , Hu H.M. , Langen E. , Low L.K. , Brummett C.M. , Waljee J.F. , Bauer M.E.
Published: August 2021

(Am J Obstet Gynecol. 2020;223:566.e1–566.e13)

Reduction of opioid prescription following delivery has become a priority nationwide. Independent of mode of delivery, postpartum opioid exposure has been linked to new persistent use after delivery. This retrospective cohort study assessed rates of opioid prescription during pregnancy to understand the impact on long-term opioid use, including new persistent opioid use (NPOU) and long-term opioid use after delivery.
Maternal Mortality in the United States: Research Gaps, Opportunities, and Priorities
Authors: Chinn J.J. , Eisenberg E. , Dickerson S.A. , King R.B. , Chakhtoura N. , Lim I.A.L. , Grantz K.L. , Lamar C. , Bianchi D.W.
Published: August 2021

(Am J Obstet Gynecol. 2020;223:568.e1–568.e5)

There has been a rise of pregnancy-related mortality in the United States between 1987 and 2016, with an increase from 7.2 to 16.9 maternal deaths per 100,000 live births. Of these maternal deaths, racial disparities exist. Non-Hispanic black women experience .3 times the number of maternal deaths as non-Hispanic white women. In addition, more than half of the annual maternal deaths within the United States are attributed to preventable causes. As research is an essential component of discovering causes and reversing the rise of maternal morbidity rates, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) convened 2 workshops in 2019 to identify research gaps, examine current science, and focus on research priorities for this topic.
Effect of Inadequate Sleep on Clinician Performance
Authors: Saadat H.
Published: August 2021

(Anesth Analg. 2021;132:1338–1343)

Sleep deprivation (SD) can have adverse effects on cognitive function and decision-making, and lead to motor vehicle accidents and devastating health and environmental disasters. Sleep occurs in 4 stages in cycles lasting 90 to 120 minutes. Most adults need 7 to 9 hours per night. There are a number of sleep disturbances and disorders, including insomnias, excessive somnolence (DOES), and parasomnias. SD is categorized into long-term SD (>45 h), short-term SD (≤45 h), and partial SD (<7 h/24 h).
The Effect of the No Pain Labor and Delivery–Global Health Initiative on Cesarean Delivery and Neonatal Outcomes in China: An Interrupted Time-series Analysis
Authors: Drzymalski D.M. , Guo J.-C. , Qi X.-Q. , Tsen L.C. , Sun Y. , Ouanes J.-P.P. , Xia Y. , Gao W.D. , Ruthazer R. , Hu F. , Hu L.-Q.
Published: August 2021

(Anesth Analg. 2021;132:698–706)

The proportion of births by cesarean delivery (CD) has been increasing in China, to an average of 34.6% in 2014, ranging from 4% to 62.5% across provinces. CD is associated with maternal and neonatal risks, and the Chinese government has begun initiatives to lower the rate of CD. The No Pain Labor and Delivery–Global Health Initiative (NPLD-GHI) conducts week-long training programs using an interdisciplinary team to teach advances of obstetrics, neonatology, and anesthesiology, aiming to help lower the rate of CD and improve outcomes. This study examined the effects of the NPLD-GHI program in a large hospital in a rural province, primarily focusing on the rate of CD.
The Effects of Nitroglycerin on the Oxytocin Dose-response Profile in Oxytocin-desensitized and Naive Human Myometrium: An In Vitro Study
Authors: Jayasooriya G.S. , Carvalho J.C.A. , Luca A. , Balki M.
Published: August 2021

(Anesth Analg. 2021;132:231–239)

During delivery, nitroglycerin is used clinically to reduce uterine tone, in situations such as uterine hyperstimulation or difficult fetal extraction. Oxytocin (OT) is an uterotonic used to induce contractions and after delivery to prevent postpartum hemorrhage. OT exposure in myometrium can cause desensitization of OT receptors. A previous study by Lau et al1 found OT can achieve satisfactory uterine tone following the use of nitroglycerin myometrium in vitro, but it is not clear if the use of nitroglycerin affects the dose needed to reestablish uterine tone. This in vitro study investigates whether nitroglycerin alters the OT dose-response in OT-desensitized and OT-naive tissues.
Adaptation of an Obstetric Anesthesia Service for the Severe Acute Respiratory Syndrome Coronavirus-2 Pandemic: Description of Checklists, Workflows, and Development Tools
Authors: Li Y. , Ciampa E.J. , Zucco L. , Levy N. , Colella M. , Golen T. , Shainker S.A. , Lunderberg J.M. , Ramachandran S.K. , Hess P.E.
Published: August 2021

(Anesth Analg. 2021;132:31–37)

Health care workers have a significant risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure and infection. Current guidelines detailing the management of patients with confirmed or suspected SARS-CoV-2 infection do not adequately address preparations aimed at mitigating SARS-CoV-2 infection risks associated with procedures specific to obstetric anesthesia. There is a need for workflows and checklists that maintain safety, provide effective care for patients with or without SARS-CoV-2 infection, and reduce waste during labor analgesia, cesarean neuraxial anesthesia, general anesthesia, and situations such as conversion of labor analgesia to cesarean anesthesia. This report discusses the COVID response workflows developed by the Beth Israel Deaconess Medical Center in Boston.
Good at Heart: Developing a Tertiary Perinatal Cardiac Service; the First Eight Years of Experience
Authors: Heland S. , de Chellis A. , Rieder W. , Sleeman M. , Johns J. , Lancefield T. , Robinson A. , Fung A. , Walker S.
Published: August 2021

(Aust N Z J Obstet Gynaecol. 2020;60:760–765)

Improved obstetric care in high income countries has reduced overall maternal mortality and morbidity, but an increasing trend of cardiac disease contribution to adverse maternal outcomes has emerged. In developed countries, cardiac disease is now the most common cause of indirect maternal death. In 2009, Mercy Hospital for Women created a multidisciplinary perinatal cardiac service to improve outcomes in parturients with congenital and acquired cardiac disease. This study describes outcomes after the first 8 years of that service and summarizes potential needs of tertiary care related to the significant risks that maternal heart disease poses to fetal and maternal well-being.
European Minimum Standards for Obstetric Analgesia and Anaesthesia Departments: An Experts’ Consensus
Authors: Guasch E. , Brogly N. , Mercier F.J. , Ioscovich A. , Weiniger C.F. , Lucas N. , Chassard D. , Kranke P. , Whitaker D. , Geldner G. , Sabelnikovs O. , de Robertis E.
Published: August 2021

(Eur J Anaesthesiol. 2020;37:1115–1125)

Currently, no minimum standards of anesthesia care for obstetric patients have been defined in Europe or the European Union. Moreover, obstetric anesthesia standards vary widely within and between countries. Providing recommendations for obstetric anesthesia care helps improve maternal safety and quality care across Europe.
Fluid Loading Therapy to Prevent Spinal Hypotension in Women Undergoing Elective Cesarean Section: Network Meta-analysis, Trial Sequential Analysis and Meta-regression
Authors: Rijs K. , Mercier F.J. , Lucas D.N. , Rossaint R. , Klimek M. , Heesen M.
Published: August 2021

(Eur J Anaesthesiol. 2020;37:1126–1142)

Up to 80% of women experience hypotension after spinal anesthesia without prophylaxis for cesarean delivery (CD). The recommended approach to prevent hypotension is a phenylephrine infusion at the time of spinal anesthesia. Fluid-loading strategies can also play a part in maintaining hemodynamic stability. While some meta-analyses exist on the use of fluid therapy to prevent hypotension due to spinal anesthesia, it is unclear whether these studies had sufficient power to draw conclusions. The aim of this study was to employ network meta-analysis with trial sequence analysis and meta-regression to determine the optimal fluid-loading strategy to prevent hypotension due to spinal anesthesia in elective CDs.
Transversus Abdominis Plane Block Compared With Wound Infiltration for Postoperative Analgesia Following Cesarean Delivery: A Systematic Review and Network Meta-analysis
Authors: Sultan P. , Patel S.D. , Jadin S. , Carvalho B. , Halpern S.H.
Published: August 2021

(Can J Anesth/J Can Anesth. 2020;67:1710–1727)

Multimodal analgesia including long-acting neuraxial opioids is the first choice for postoperative analgesia after cesarean delivery (CD). When contraindications to neuraxial anesthesia are present or long-acting opioids are omitted, then post-CD analgesia may consist of local anesthetic techniques, such as transversus abdominis plane (TAP) blocks or wound infiltration (WI). These techniques have been shown to reduce pain scores and opioid requirements following CD, but studies comparing the two have had conflicting results. In this systematic review and network meta-analysis (NMA), the analgesic efficacy and side effects of TAP blocks were compared to WI following CD in the absence of long-acting neuraxial opioids.
Breathing for 2
Authors: Rudder M. , Russo M. , Ventetuolo C.E.
Published: August 2021

(N Engl J Med. 2021;384:61–68)

This feature contained details about 1 patient’s case, with a clinician’s commentary interspersed throughout. The case was that of a 29-year-old woman at 26 weeks gestation with undifferentiated connective tissue disease, presenting with cough, and shortness of breath.
The Surgeon and the Mother
Authors: Heather Carmichael
Published: August 2021

(N Engl J Med. 2021;384:302–303)
Function and regulation of muscle stem cells in skeletal muscle development and regeneration: a narrative review
Authors: Zhu Han , Lin Xin , Diao Yarui
Published: August 2021

Skeletal muscle plays an essential role in generating the mechanical force necessary to support the movement of our body and daily exercise. Compared with cardiac and smooth muscle, in mammals, skeletal muscle exhibits remarkable regenerative capacity in response to damage. Muscle stem cells, also known as satellite cells, directly contribute to regeneration. Here, we review primary and secondary myogenesis processes with a focus on muscle stem cells, as well as the function and regulation of muscle stem cells in adult muscle regeneration in mammals.
Association of Social Media Use on Sleep Quality and Performance Among Collegiate Athletes
Authors: Watkins Rhonda A. , Sugimoto Dai , Hunt Danielle , Oldham Jessie , Cacolice Paul A. , Stracciolini Andrea
Published: August 2021

Objective:

(1) To examine the effect of social media (SM) use on sleep quality and (2) to determine the effect of SM on competition performance among college athletes.

Design:

Cross-sectional study.

Setting:

Two local Division III colleges, MA, USA.

Participants:

National Collegiate Athletic Association Division III swim and track and field athletes.

Intervention:

Data were collected onsite through an SM use form, the lifestyle survey, and the Patient-Reported Outcomes Measurement Information System Sleep Disturbance Questionnaire. Participants were divided into 3 groups based on their SM volume: (1) less active SM users (≤2 h/d), (2) moderately active SM users (>2-≤5 h/d), and (3) active SM users (>5 h/d) for analysis.

Main Outcome Measures:

Sleep quality and sport performance data collected through publicly available competition results. The independent variable, SM volume (hours of SM use per day over 7 days), was collected using the iPhone screen time function.

Results:

The cohort consisted of 40 male track and field athletes and 47 female track and field (37, 79%) and swimming (10, 21%) athletes. Mean SM use was 4.6 ± 3.4 h/d. The sleep quality of active SM users was worse than less active SM users (P = 0.033). There was an independent association between increased Facebook time and poor performance after adjusting confounders (adjusted odds ratio: 0.990, 95% confidence interval: 0.981-0.999, P = 0.049).

Conclusions:

High SM use has a negative impact on sleep quality and may hinder competition performance among college athletes. These findings may have implications for developing SM use guidelines for college athletes to improve their sleep quality and performance.
Does Blood-Brain Barrier Disruption Define the Glioma Extracellular Metabolome?
Authors: Riviere-cazaux Cecile , Carlstrom Lucas P. , Rajani Karishma , Munoz-casabella Amanda , Rahman Masum , Gharibi-Loron Ali , Brown Desmond A. , Miller Kai J , White Jaclyn J. , Himes Benjamin T. , Jusue-Torres Ignacio , Ikram Samar , Ransom Seth , Hirte Renee , Oh Ju-Hee , Elmquist William F. , Sarkaria Jann N. , Vaubel Rachael A. , Rodriguez Moses , Warrington Arthur , Kizilbash Sani H. , Burns Terry C.
Published: August 2021

Background

The extracellular microenvironment modulates cancer behavior. Although radiographic contrast enhancement is an ominous finding in gliomas, it remains unclear if the associated blood-brain barrier disruption merely reflects or functionally supports tumor aggressiveness.

Methods

We utilized intra-operative microdialysis to sample the extracellular metabolome of radiographically diverse regions during fifteen neurosurgical resections. The global extracellular metabolome of recovered microdialysate was evaluated via ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) and assessed using enrichment and correlation analyses.

Results

Among 162 named metabolites identified via ultra-performance liquid chromatography tandem mass spectrometry, guanidinoacetate (GAA), was 126.32x higher in enhancing tumor than in adjacent brain. 48 additional metabolites were 2.05-10.18x more abundant in enhancing tumor than brain. With exception of GAA, and 2-HG in IDH-mutant gliomas, differences between non-enhancing tumor and brain microdialysate were comparatively modest and less consistent. The enhancing but not the non-enhancing glioma metabolome was significantly enriched for plasma-associated metabolites largely comprising amino acids and carnitines.

Conclusions

Our findings suggest that metabolite diffusion through a disrupted blood-brain barrier may largely define the enhancing extracellular glioma metabolome. Future studies are needed to determine how the altered extracellular metabolome impacts glioma behavior.
Comparison of Object Detection Approaches Applied to Field Images of Papanicolaou Stained Cytology Slides
Authors: Victória Matias André , Cerentini Allan , Buschetto Macarini Luiz Antonio , Atkinson Amorim João Gustavo , Daltoé Felipe Perozzo , von Wangenheim Aldo
Published: August 2021

Papanicolaou is an inexpensive and non-invasive method, generally applied to detect cervical cancer, that can also be useful to detect cancer on oral cavities. Although oral cancer is considered a global health issue with 350.000 people diagnosed over a year it can successfully be treated if diagnosed at early stages. The manual process of analyzing cells to detect abnormalities is time-consuming and subject to variations in perceptions from different professionals. To evaluate a possible solution to the automation of this process, in this paper we employ the object detection deep learning approach in the analysis of this type of image using 3 models: RetinaNet, Faster R-CNN, and Mask R-CNN. We trained and tested the models using images from 6 cytology slides (4 cancer cases and 2 healthy samples) and our results show that Mask R-CNN was the best model for localization and classification of nuclei with an IoU of 0.51 and recall of abnormal nuclei of 0.67.
How Strong Is a Mother’s Love? Exploring the Mediating Role of Mother-Child Relationship Quality on the Link between Child Abuse Experiences and Adult Intimate Partner Violence Perpetration
Authors: Yin Shuya , McLay Molly M.
Published: August 2021

Purpose

Intimate partner violence (IPV) has detrimental effects on individuals’ physical and mental health. Intergenerational violence transmission theory posits that child abuse (CA) is an important determinant of later IPV perpetration due to socially learned aggression and expectations of violence in romantic relationships. However, less research exists on family protective factors like the mother-child relationship, the strength of which may mediate this link. The present study explored the association between mother-child relationships, child abuse, and adult IPV perpetration—specifically, whether mother–child relationship quality mediated the effects on the link between child abuse and later IPV.

Methods

This study analyzed data from individuals who completed Waves I and Wave IV of the National Longitudinal Study of Adolescent Health (N=3718 respondents). Structural equation modeling (SEM) was used to investigate mediation dynamics between CA, mother-child relationship, and adult IPV perpetration.

Results

Structural equation model fit the data well (CFI = .918, RMSEA = .051 [.045, .057]). The mediation model revealed that the direct effect of childhood abuse on IPV was .067 (p<.001), while the indirect effect of childhood abuse on IPV (i.e., the effect operating through the mother-child relationship) was .005 (p<.001).

Conclusions

While CA remains a significant risk factor for adult IPV perpetration, findings suggest that high-quality mother-child relationships may have a buffering effect and aid in preventing intergenerational violence transmission. Continued efforts to research, fund, and implement interventions that build healthy family dynamics are needed to support traumatized children into adulthood and end intergenerational violence.
Mapping the human corticoreticular pathway with multimodal delineation of the gigantocellular reticular nucleus and high-resolution diffusion tractography
Authors: Boyne Pierce , DiFrancesco Mark , Awosika Oluwole O. , Williamson Brady , Vannest Jennifer
Published: August 2021

The corticoreticular pathway (CRP) is a major motor tract that provides volitional input to the reticular formation motor nuclei and may be an important mediator of motor recovery after central nervous system damage. However, its cortical origins, trajectory and laterality are incompletely understood in humans. This study aimed to map the human CRP and generate an average CRP template in standard MRI space. Following recently established guidelines, we manually delineated the primary reticular formation motor nucleus (gigantocellular reticular nucleus [GRN]) using several group-mean MRI contrasts from the Human Connectome Project (HCP). CRP tractography was then performed with HCP diffusion-weighted MRI data (N=1,065) by selecting diffusion streamlines that reached both the frontal cortex and GRN. Corticospinal tract (CST) tractography was also performed for comparison. Results suggest that the human CRP has widespread origins, which overlap with the CST across most of the motor cortex and include additional exclusive inputs from the medial and anterior prefrontal cortices. The estimated CRP projected through the anterior and posterior limbs of the internal capsule before partially decussating in the midbrain tegmentum and converging bilaterally on the pontomedullary reticular formation. Thus, the CRP trajectory appears to partially overlap the CST, while being more distributed and anteromedial to the CST in the cerebrum before moving posterior to the CST in the brainstem. These findings have important implications for neurophysiologic testing, cortical stimulation and movement recovery after brain lesions. We expect that our GRN and tract maps will also facilitate future CRP research.

HIGHLIGHTS

The corticoreticular pathway (CRP) is a major tract with poorly known human anatomy

We mapped the human CRP with diffusion tractography led by postmortem & animal data

The CRP appears to originate from most of the motor cortices and further anterior

The estimated CRP had distributed and bilateral projections to the brainstem

These findings have important implications for motor recovery after brain lesions
Effectiveness of surface-based North Atlantic right whale detection methods for vessel strike mitigation
Authors: Baille Loïcka M.R. , Zitterbart Daniel P.
Published: August 2021

Increasing commercial and recreational use of the world’s ocean leads to growing concerns on vessel and marine mammal encounters. For endangered species, like the North Atlantic right whale (NARW), vessel strikes can be responsible for the majority of the recorded deaths. Reducing the number of vessel strikes is key to improve North Atlantic right whale protection and a number of mitigation methods have been proposed and implemented. In this manuscript, we developed an agent-based model to assess the effectiveness of surface-based whale detection methods for vessel strike mitigation. We find that the effectiveness of such systems varies highly depending on the vessel’s speed and maneuverability. We also find that if vessel-based whale detection systems are used in conjunction with other mitigation measures such as general speed restrictions, they can be very effective and could lead to a significant decrease in vessel strikes when deployed at a large-scale.
Neural Correlates and Functional Cognitive Maps in Breast Cancer Survivors Receiving Different Chemotherapy Regimens; a QEEG/HEG – based Investigation
Authors: Gharamaleki Maryam Vasaghi , Mousavi Seyedeh Zahra , Owrangi Maryam , Gholamzadeh Mohammad Javad , Kamali Ali-Mohammad , Dehghani Mehdi , Chakrabarti Prasun , Nami Mohammad
Published: August 2021

Background

Post-chemotherapy cognitive impairment commonly known as “chemobrain” or “chemofog” is a well-established clinical disorder affecting various cognitive domains including attention, visuospatial working memory, executive function, etc. Although several studies have confirmed the chemobrain in recent years, scant experiments have evaluated the potential neurotoxicity of different chemotherapy regimens and agents. In this study, we aimed to evaluate the extent of attention deficits, one of the commonly affected cognitive domains, among breast cancer patients treated with different chemotherapy regimens through neuroimaging techniques.

Methods

Breast cancer patients treated with two commonly prescribed chemotherapy regimens, AC-T and TAC, and healthy volunteers were recruited. Near-infrared hemoencephalography (nirHEG) and quantitative electroencephalography (qEEG) assessments were recorded for each participant at rest and during task performance to compare the functional cortical changes associated with each chemotherapy regimen.

Results

The qEEG analysis revealed increased power of high alpha/low beta or sensorimotor rhythm (SMR) frequency in left fronto-centro-parietal regions involved in dorsal and ventral attention networks (DAN and VAN) in the AC-T-treated group comparing to the TAC and control group. The AC-T group also had the highest current source density (CSD) values in DAN and VAN-related centers in 10 and 15 Hz associated with the lowest Z-scored FFT coherence in the mentioned regions.

Conclusions

The mentioned findings revealed increased cognitive workload and lack of cognitive ease in breast cancer patients treated with the AC-T regimen proposing the presumable neurotoxic sequelae of this chemotherapy regimen in comparison with the TAC regimen.
Explant analysis of Utah electrode arrays implanted in human cortex for brain-computer-interfaces
Authors: Woeppel Kevin , Hughes Christopher , Herrera Angelica J. , Eles James , Tyler-Kabara Elizabeth C. , Gaunt Robert A. , Collinger Jennifer L. , Cui Xinyan Tracy
Published: August 2021

Brain-computer interfaces are being developed to restore movement for people living with paralysis due to injury or disease. Although the therapeutic potential is great, long-term stability of the interface is critical for widespread clinical implementation. While many factors can affect recording and stimulation performance including electrode material stability and host tissue reaction, these factors have not been investigated in human implants. In this clinical study, we sought to characterize the material integrity and biological tissue encapsulation via explant analysis in an effort to identify factors that influence electrophysiological performance.

We examined a total of six Utah arrays explanted from two human participants involved in intracortical BCI studies. Two Pt arrays were implanted for 980 days in one participant (P1) and two Pt and two iridium oxide (IrOx) arrays were implanted for 182 days in the second participant (P2). We observed that the recording quality followed a similar trend in all 6 arrays with an initial increase in peak-to-peak voltage during the first 30-40 days and gradual decline thereafter in P1.

Using optical and two-photon microscopy (TPM) we observed a higher degree of tissue encapsulation on both arrays implanted for longer durations in participant P1. We then used scanning electron microscopy and energy dispersive X-ray spectroscopy to assess material degradation. All measures of material degradation for the Pt arrays were found to be more prominent in the participant with a longer implantation time. Two IrOx arrays were subjected to brief survey stimulations, and one of these arrays showed loss of iridium from majority of the stimulated sites. Recording performance appeared to be unaffected by this loss of iridium, suggesting that the adhesion of IrOx coating may have been compromised by the stimulation, but the metal layer did not detach until or after array removal.

In summary, both tissue encapsulation and material degradation were more pronounced in the arrays that were implanted for a longer duration. Additionally, these arrays also had lower signal amplitude and impedance. New biomaterial strategies that minimize fibrotic encapsulation and enhance material stability should be developed to achieve high quality recording and stimulation for longer implantation periods.
Dose-effect relationship of ginger interposed moxibustion for allergic rhinitis: study protocol for a randomised, placebo-controlled and parallel clinical trial
Authors: Wen Yunfan , Wang Wen , Ni Yingna , Gui Yeqiao , Hu Zhihai , Wang Yi , Han Mengke , Zhang Dongmin , Shu Shi , Zhou Shuang
Published: August 2021

Introduction

Allergic rhinitis has a severe impact on patients’ life quality, and the incidence rate keeps increasing. Moxibustion is widely used for treating allergic rhinitis, and quantity is the basis of moxibustion efficacy. The purpose of this study is to evaluate the relationship between the different quantities of moxibustion and the efficacy of moxibustion in the treatment of allergic rhinitis. This study may be conductive to the standardization of moxibustion and furnish the mechanism of dose-effect relationship of moxibustion with data and new ideas.

Methods and analysis

This randomized, placebo-controlled clinical trial will include 33 patients with allergic rhinitis who will be randomly assigned into three groups in a 1:1:1 ratio: high-dose moxibustion group, low-dose moxibustion group and sham moxibustion control group. All groups will be treated once every other day, 20 days for one treatment course. And the patients will receive treatment for 2 courses with an interval of 2 days between courses. We will conduct a follow-up 30 days later after completion of treatments. The primary outcome measure is Total Nasal Symptom Score, carried out at baseline, 3, 6 and 10 weeks. Secondary outcome measure is Rhino Conjunctivitis Quality of Life Questionnaire, carried out at baseline, 6 and 10 weeks.

Ethics and dissemination

This trail has been approved by the IRB of Shanghai TCM-Integrated Hospital, Shanghai University of TCM. The results of the trial will be disseminated in peer-reviewed journals.

Trial registration number

ChiCTR2100050373; Pre-results.

Strengths and limitations of this study

A randomised, placebo-controlled and parallel clinical trial will be conducted to test if ginger interposed moxibustion would have curative effect on allergic rhinitis and reveal the preliminary dose-effect relationship of moxibustion.

This study will set high-dose moxibustion group and low-dose moxibustion group to test if more quantities of ginger interposed moxibustion would achieve better therapeutic effects on allergic rhinitis.

Further study should be carried out to test if the curative effect of ginger interposed moxibustion would be positively correlated with the quantities.
Poly(A) tail length is a major regulator of maternal gene expression during the mammalian oocyte-to-embryo transition
Authors: Liu Yusheng , Nie Hu , Zhang Chuanxin , Hou Zhenzhen , Wang Jiaqiang , Lu Falong
Published: August 2021

Transcription is silent during the mammalian oocyte-to-embryo transition (OET) until zygotic genome activation (ZGA). Therefore, the OET relies on post-transcriptional regulation of maternal mRNA, among which poly(A) tail lengths have been found to regulate translation for a small number of genes1–3. However, transcriptome-wide poly(A) tail length dynamics and their role in gene expression during the mammalian OET remain unknown. Here, we quantified transcriptome-wide mRNA poly(A) tail length dynamics during the mammalian OET using PAIso-seq1 and PAIso-seq24,5, two methods with different underlying principles that preserve the poly(A) tail information. We revealed that poly(A) tail length was highly dynamic during the mouse OET, and Btg4 is responsible for global maternal mRNA deadenylation. We found that the poly(A) tail length positively associated with translational efficiency transcriptome-wide in mouse oocytes. In addition, genes with different alternative polyadenylation isoforms show longer poly(A) tails for isoforms with distal polyadenylation sites compared to those with proximal polyadenylation sites in mouse, rat, pig and human oocytes after meiotic resumption, which is not seen in cultured cell lines. Surprisingly, mammalian embryos, namely mouse, rat, pig, and human embryos, all experience highly conserved global mRNA re-polyadenylation after fertilization, providing molecular evidence that the early embryo development before ZGA is driven by re-polyadenylated maternal mRNAs rather than newly transcribed mRNAs. Together, our study reveals the conserved mRNA poly(A) tail length landscape. This resource can be used for exploring spatiotemporal post-transcriptional regulation throughout the mammalian OET.
Disruption of the grid cell network in a mouse model of early Alzheimer’s disease
Authors: Ying Johnson , Keinath Alexandra T. , Lavoie Raphael , Vigneault Erika , Mestikawy Salah El , Brandon Mark P.
Published: August 2021

Early-onset familial Alzheimer’s disease (AD) is marked by an aggressive buildup of amyloid beta (Aβ) proteins, yet the neural circuit operations impacted during the initial stages of Aβ pathogenesis remain elusive. Here, we report a coding impairment of the medial entorhinal cortex (MEC) grid cell network in a transgenic mouse model of familial AD that over-expresses Aβ throughout the hippocampus and entorhinal cortex. Grid cells showed reduced spatial periodicity, spatial stability, and synchrony with interneurons and head-direction cells. In contrast, the spatial coding of non-grid cells within the MEC, and place cells within the hippocampus, remained intact. Grid cell deficits emerged at the earliest incidence of Aβ fibril deposition and coincided with impaired spatial memory performance in a path integration task. These results demonstrate that widespread Aβ-mediated damage to the entorhinal-hippocampal circuit results in an early impairment of the entorhinal grid cell network.
Neural evidence for the successor representation in choice evaluation
Authors: Russek Evan M. , Momennejad Ida , Botvinick Matthew M. , Gershman Samuel J. , Daw Nathaniel D.
Published: August 2021

Evaluating choices in multi-step tasks is thought to involve mentally simulating trajectories. Recent theories propose that the brain simplifies these laborious computations using temporal abstraction: storing actions’ consequences, collapsed over multiple timesteps (the Successor Representation; SR). Although predictive neural representations and, separately, behavioral errors (“slips of action”) consistent with this mechanism have been reported, it is unknown whether these neural representations support choices in a manner consistent with the SR. We addressed this question by using fMRI to measure predictive representations in a setting where the SR implies specific errors in multi-step expectancies and corresponding behavioral errors. By decoding measures of state predictions from sensory cortex during choice evaluation, we identified evidence that behavioral errors predicted by the SR are accompanied by predictive representations of upcoming task states reflecting SR predicted erroneous multi-step expectancies. These results provide neural evidence for the SR in choice evaluation and contribute toward a mechanistic understanding of flexible and inflexible decision making.
Adaptation of anammox bacteria to low temperature via gradual acclimation and cold shocks: distinctions in protein expression, membrane composition and activities
Authors: Kouba V. , Vejmelkova D. , Zwolsman E. , Hurkova K. , Navratilova K. , Laureni M. , Vodickova P. , Podzimek T. , Hajslova J. , Pabst M. , van Loosdrecht M.C.M. , Bartacek J. , Lipovova P. , Weissbrodt D.G.
Published: August 2021

Anammox bacteria enable an efficient removal of nitrogen from sewage in processes involving partial nitritation and anammox (PN/A) or nitrification, partial denitrification, and anammox (N-PdN/A). In mild climates, anammox bacteria must be adapted to ≤15 °C, typically by gradual temperature decrease; however, this takes months or years. To reduce the time necessary for the adaptation, an unconventional method of ‘cold shocks’ is promising, involving hours-long exposure of anammox biomass to extremely low temperatures. We compared the efficacies of gradual temperature decrease and cold shocks to increase the metabolic activity of anammox (fed batch reactor, planktonic “Ca. Kuenenia”). We assessed the cold shock mechanism on the level of protein expression (quantitative shot-gun proteomics, LC-HRMS/MS) and structure of membrane lipids (UPLC-HRMS/MS). The shocked culture was more active (0.66±0.06 vs 0.48±0.06 kg-N/kg-VSS/d) and maintained the relative content of N-respiration proteins at levels consistent levels with the initial state, whereas the content of these proteins decreased in gradually acclimated culture. Cold shocks also induced a more efficient up-regulation of cold shock proteins (e.g. CspB, TypA, ppiD). Ladderane lipids characteristic for anammox evolved to a similar end-point in both cultures which confirms their role in anammox bacteria adaptation to cold and indicates a three-pronged adaptation mechanism involving ladderane lipids (ladderane alkyl length, introduction of shorter non-ladderane alkyls, polar headgroup). Overall, we show the outstanding potential of cold shocks for low-temperature adaptation of anammox bacteria and provide yet unreported detailed mechanisms of anammox adaptation to low temperatures.

Highlights

Anammox bacteria were adapted to low T by gradual acclimation and cold shocks

The shocked culture was more active (0.66±0.06 vs 0.48±0.06 kg-N/kg-VSS/d)

N-respiration proteins content decreased in gradually acclimated bacteria

Several cold shock proteins were upregulated more efficiently by cold shocks

At ↓T, anammox adjusted ladderane membrane lipid composition in three aspects

Graphical abstract
NBI-921352, a First-in-Class, NaV1.6 Selective, Sodium Channel Inhibitor That Prevents Seizures inScn8aGain-of-Function Mice, and Wild-Type Mice and Rats
Authors: Johnson JP , Focken Thilo , Khakh Kuldip , Tari Parisa Karimi , Dube Celine , Williams Aaron , Andrez Jean-Christophe , Bankar Girish , Bogucki David , Burford Kristen , Chang Elaine , Chowdhury Sultan , Dean Richard , de Boer Gina , Decker Shannon , Dehnhardt Christoph , Feng Mandy , Gong Wei , Goodchild Samuel J , Grimwood Michael , Hasan Abid , Hussainkhel Angela , Jia Qi , Lee Stephanie , Li Jenny , Lin Sophia , Lindgren Andrea , Lofstrand Verner , Mezeyova Janette , Namdari Rostam , Nelkenbrecher Karen , Shuart Noah Gregory , Sojo Luis , Sun Shaoyi , Taron Matthew , Waldbrook Matthew , Weeratunge Diana , Wesolowski Steven , Wilson Michael , Xie Zhiwei , Yoo Rhena , Young Clint , Zenova Alla , Zhang Wei , Cutts Alison J , Sherrington Robin P , Pimstone Simon N , Winquist Raymond , Cohen Charles J , Empfield James R
Published: August 2021

NBI-921352 (formerly XEN901) is a novel sodium channel inhibitor designed to specifically target NaV1.6 channels. Such a molecule provides a precision-medicine approach to targetSCN8A-related epilepsy syndromes (SCN8A-RES), where gain-of-function (GoF) mutations lead to excess NaV1.6 sodium current, or other indications where NaV1.6 mediated hyper-excitability contributes to disease (Gardella and Moller, 2019; Johannesen et al., 2019; Veeramah et al., 2012). NBI-921352 is a potent inhibitor of NaV1.6 (IC500.051 µM), with exquisite selectivity over other sodium channel isoforms (selectivity ratios of 756X for NaV1.1, 134X for NaV1.2, 276X for NaV1.7, and >583X for NaV1.3, NaV1.4, and NaV1.5). NBI-921352 is a state-dependent inhibitor, preferentially inhibiting activated (inactivated or open) channels. The state dependence leads to potent stabilization of inactivation, inhibiting NaV1.6 currents, including resurgent and persistent NaV1.6 currents, while sparing the closed/rested channels. The isoform-selective profile of NBI-921352 led to a robust inhibition of action-potential firing in glutamatergic excitatory pyramidal neurons, while sparing fast-spiking inhibitory interneurons, where NaV1.1 predominates. Oral administration of NBI-921352 prevented electrically induced seizures in aScn8aGoF mouse, as well as in wild-type mouse and rat seizure models. NBI-921352 was effective in preventing seizures at lower brain and plasma concentrations than commonly prescribed sodium channel inhibitor antiseizure medicines (ASMs) carbamazepine, phenytoin, and lacosamide. NBI-921352 was well tolerated at higher multiples of the effective plasma and brain concentrations than those ASMs. NBI-921352 is entering phase II proof-of-concept trials for the treatment ofSCN8A-developmental epileptic encephalopathy (SCN8A-DEE) and adult focal-onset seizures.
Novel System to Monitor In Vivo Neural Graft Activity After Spinal Cord Injury
Authors: Ago Kentaro , Nagoshi Narihito , Imaizumi Kent , Kitagawa Takahiro , Kawai Momotaro , Kajikawa Keita , Shibata Reo , Kamata Yasuhiro , Kojima Kota , Shinozaki Munehisa , Kondo Takahiro , Iwano Satoshi , Miyawaki Atsushi , Ohtsuka Masanari , Bito Haruhiko , Kobayashi Kenta , Shibata Shinsuke , Shindo Tomoko , Kohyama Jun , Matsumoto Morio , Nakamura Masaya , Okano Hideyuki
Published: August 2021

Expectations for neural stem/progenitor cell (NS/PC) transplantation as a treatment for spinal cord injury (SCI) are increasing. However, whether and how grafted cells are incorporated into the host neural circuit and contribute to motor function recovery remain unknown. The aim of this project was to establish a novel non-invasive in vivo imaging system to visualize the activity of neural grafts by which we can simultaneously demonstrate the circuit-level integration between the graft and host, and the contribution of graft neuronal activity to host behaviour. We introduced Akaluc, a newly engineered luciferase, under control of a potent neuronal activity-dependent synthetic promoter, E-SARE, into NS/PCs and engrafted the cells into SCI model mice. Through the use of this system, we reveal that the activity of grafted cells was integrated with host behaviour and driven by host neural circuit inputs. This non-invasive system is expected to help elucidate the therapeutic mechanism of cell transplantation treatment for SCI and determine better therapy techniques that maximize the function of cells in the host circuit.