Regulated Proteolysis of MutSγ Controls Meiotic Crossing Over.

Crossover recombination is essential for accurate chromosome segregation during meiosis. The MutSγ complex, Msh4-Msh5, facilitates crossing over by binding and stabilizing nascent recombination intermediates. We show that these activities are governed by regulated proteolysis. MutSγ is initially inactive for crossing over due to an N-terminal degron on Msh4 that renders it unstable by directly targeting proteasomal degradation. Activation of MutSγ requires the Dbf4-dependent kinase Cdc7 (DDK), which directly phosphorylates and thereby neutralizes the Msh4 degron. Genetic requirements for Msh4 phosphorylation indicate that DDK targets MutSγ only after it has bound to nascent joint molecules (JMs) in the context of synapsing chromosomes. Overexpression studies confirm that the steady-state level of Msh4, not phosphorylation per se, is the critical determinant for crossing over. At the DNA level, Msh4 phosphorylation enables the formation and crossover-biased resolution of double-Holliday Junction intermediates. Our study establishes regulated protein degradation as a fundamental mechanism underlying meiotic crossing over.

New bio-based monomers: tuneable polyester properties using branched diols from biomass.

A family of monomers, including 2,5-hexandiol, 2,7-octandiol, 2,5-furandicarboxylic acid (FDCA), terephthalic acid (TA), and branched-chain adipic and pimelic acid derivatives, all find a common derivation in the biomass-derived platform molecule 5-(chloromethyl)furfural (CMF). The diol monomers, previously little known to polymer chemistry, have been combined with FDCA and TA derivatives to produce a range of novel polyesters. It is shown that the use of secondary diols leads to polymers with higher glass transition temperatures (Tg) than those prepared from their primary diol equivalents. Two methods of polymerisation were investigated, the first employing activation of the aromatic diacids via the corresponding diacid chlorides and the second using a transesterification procedure. Longer chain diols were found to be more reactive than the shorter chain alternatives, generally giving rise to higher molecular weight polymers, an effect shown to be most pronounced when using the transesterification route. Finally, novel diesters with high degrees of branching in their hydrocarbon chains are introduced as potential monomers for possible low surface energy materials applications.

Corticosteroids compromise survival in glioblastoma.

Glioblastoma is the most common and most aggressive primary brain tumour. Standard of care consists of surgical resection followed by radiotherapy and concomitant and maintenance temozolomide (temozolomide/radiotherapy→temozolomide). Corticosteroids are commonly used perioperatively to control cerebral oedema and are frequently continued throughout subsequent treatment, notably radiotherapy, for amelioration of side effects. The effects of corticosteroids such as dexamethasone on cell growth in glioma models and on patient survival have remained controversial. We performed a retrospective analysis of glioblastoma patient cohorts to determine the prognostic role of steroid administration. A disease-relevant mouse model of glioblastoma was used to characterize the effects of dexamethasone on tumour cell proliferation and death, and to identify gene signatures associated with these effects. A murine anti-VEGFA antibody was used in parallel as an alternative for oedema control. We applied the dexamethasone-induced gene signature to The Cancer Genome Atlas glioblastoma dataset to explore the association of dexamethasone exposure with outcome. Mouse experiments were used to validate the effects of dexamethasone on survival in vivo Retrospective clinical analyses identified corticosteroid use during radiotherapy as an independent indicator of shorter survival in three independent patient cohorts. A dexamethasone-associated gene expression signature correlated with shorter survival in The Cancer Genome Atlas patient dataset. In glioma-bearing mice, dexamethasone pretreatment decreased tumour cell proliferation without affecting tumour cell viability, but reduced survival when combined with radiotherapy. Conversely, anti-VEGFA antibody decreased proliferation and increased tumour cell death, but did not affect survival when combined with radiotherapy. Clinical and mouse experimental data suggest that corticosteroids may decrease the effectiveness of treatment and shorten survival in glioblastoma. Dexamethasone-induced anti-proliferative effects may confer protection from radiotherapy- and chemotherapy-induced genotoxic stress. This study highlights the importance of identifying alternative agents such as vascular endothelial growth factor antagonists for managing oedema in glioblastoma patients. Beyond the established adverse effect profile of protracted corticosteroid use, this analysis substantiates the request for prudent and restricted use of corticosteroids in glioblastoma.

EMPACT syndrome: limited evidence despite a high-risk cohort.

Serious dermatologic adverse events such as erythema multiforme (EM) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) have been reported in patients receiving antiepileptic drugs (AEDs) and cranial radiotherapy (RT). Given the frequency of AED-associated rashes and the infrequency of serious dermatologic adverse events after cranial RT, we sought to further assess the prevalence of cutaneous eruptions in patients receiving an AED before and after cranial RT. We reviewed medical records of patients taking AEDs while undergoing RT for a high-grade glioma and recorded demographic, disease, and treatment parameters, as well as the development of rashes. Rashes were found in 19 % of patients taking AEDs. Phenytoin was most commonly implicated (93 %) in rash formation compared with other AEDs (P < 0.0001), both before and during RT. Most rashes (76 %) occurred before starting RT (P < 0.0001). However, of those during RT, most were associated with phenytoin compared with other AEDs (P = 0.002). One case of SJS was noted in a patient receiving phenytoin prior to RT. While rashes were slightly less prevalent in patients receiving temozolomide compared with those not receiving temozolomide (3.4 vs 4.8 %), this difference was not statistically significant (P = 0.65). Rashes are relatively common in patients receiving AEDs, with the highest incidence associated with phenytoin. However, the risk of serious dermatologic events is low. There did not appear to be an association between the receipt of cranial radiotherapy and the development of AED-associated rash with phenytoin or other AEDs.

Survival of patients treated with radiation therapy for anaplastic astrocytoma.

BACKGROUND: Anaplastic astrocytoma (AA) represents 7% of primary brain tumors in adults. Patient-, tumor-, and treatment-related factors are thought to be predictive of survival. We retrospectively assessed the association of patient-, tumor-, and treatment-related factors with survival in AA treated with radiotherapy (RT) at our institution. PATIENTS AND METHODS: Medical records of patients with AA treated with RT between 1987 and 2007 were reviewed. Patient-, tumor-, and treatment-related variables were recorded and used to assign patients to a Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA) classification. First use of chemotherapy was recorded. Log-rank tests and Cox regression models were used to assess for an association of patient-, tumor- and treatment-related factors with survival. RESULTS: One-hundred twenty-six patients were eligible for study. Median age, Karnofsky performance status, and duration of symptoms were 43 years, 90, and 8 weeks. Median radiation dose was 59.4 Gy; 61% of patients underwent tumor resection, and 17% and 41% of patients received temozolomide during and after RT. Median survival was 31 months, and 2-year survival was 58%. RTOG RPA class was associated with survival (p < 0.001), but use of temozolomide during or after RT was not (p > 0.05). CONCLUSIONS: In this retrospective study with inherent limitations, RTOG RPA classification was associated with survival. Further studies are necessary to confirm or refute this finding.

Radiotherapy and concomitant temozolomide may improve survival of elderly patients with glioblastoma.

Survival of elderly patients with glioblastoma (GBM) is poor, but improves with tumor resection and radiotherapy (RT). Concurrent temozolomide (TMZ) chemotherapy during RT improves the survival of younger patients with GBM, but the benefit in elderly patients is unclear. Medical records of patients ≥65 years old with primary GBM, histologically confirmed at Memorial Sloan-Kettering Cancer Center and treated with RT, were reviewed. Survival was associated with patient (age, performance status), tumor (single or multiple), and treatment (extent of surgery, RT field, technique, fractionation and use of concurrent TMZ) characteristics in a multivariable Cox regression model. Grade ≥3 hematologic toxicity rates were compared to reported rates in younger patients. Median age of the 291 patients studied was 71 years. Longer survival was associated with younger age, tumor resection, and concomitant TMZ and RT (p < 0.01). Concurrent TMZ and RT improved median survival of patients with favorable prognostic factors from 12 to 21 months and from 10 to 13 months in patients 65-70 and ≥71 years old, respectively. Concomitant TMZ and RT increased the 2 year OS rate from 14 to 41 % and from 5 to 24 % in patients 65-70 and ≥71 years old, respectively. Grade 3-4 thrombocytopenia was significantly more frequent in the present cohort. Survival of elderly patients with GBM may be prolonged with the use of concomitant TMZ during RT. An ongoing randomized study will determine the benefit of this approach in a prospective fashion.

Structural brain alterations associated with dyslexia predate reading onset.

Functional magnetic resonance imaging studies have reported reduced activation in parietotemporal and occipitotemporal areas in adults and children with developmental dyslexia compared to controls during reading and reading related tasks. These patterns of regionally reduced activation have been linked to behavioral impairments of reading-related processes (e.g., phonological skills and rapid automatized naming). The observed functional and behavioral differences in individuals with developmental dyslexia have been complemented by reports of reduced gray matter in left parietotemporal, occipitotemporal areas, fusiform and lingual gyrus and the cerebellum. An important question for education is whether these neural differences are present before reading is taught. Developmental dyslexia can only be diagnosed after formal reading education starts. However, here we investigate whether the previously detected gray matter alterations in adults and children with developmental dyslexia can already be observed in a small group of pre-reading children with a family-history of developmental dyslexia compared to age and IQ-matched children without a family-history (N = 20/mean age: 5:9 years; age range 5:1-6:5 years). Voxel-based morphometry revealed significantly reduced gray matter volume indices for pre-reading children with, compared to children without, a family-history of developmental dyslexia in left occipitotemporal, bilateral parietotemporal regions, left fusiform gyrus and right lingual gyrus. Gray matter volume indices in left hemispheric occipitotemporal and parietotemporal regions of interest also correlated positively with rapid automatized naming. No differences between the two groups were observed in frontal and cerebellar regions. This discovery in a small group of children suggests that previously described functional and structural alterations in developmental dyslexia may not be due to experience-dependent brain changes but may be present at birth or develop in early childhood prior to reading onset. Further studies using larger sample sizes and longitudinal analyses are needed in order to determine whether the identified structural alterations may be utilized as structural markers for the early identification of children at risk, which may prevent the negative clinical, social and psychological outcome of developmental dyslexia.

Coordinated postnatal down-regulation of multiple growth-promoting genes: evidence for a genetic program limiting organ growth.

Children grow, but adults do not. The cessation of growth in multiple organs is the end result of a progressive decline in cell proliferation beginning in early life. The mechanisms responsible for this growth deceleration are largely unknown. Using expression microarray and real-time PCR, we identified a common program of gene expression in lung, kidney, and liver during growth deceleration in juvenile rats. Gene ontology analyses and siRNA-mediated knockdown in vitro indicated that many of the down-regulated genes are growth promoting. Down-regulated genes in the program showed declining histone H3K4 trimethylation with age, implicating underlying epigenetic mechanisms. To investigate the physiological processes driving the genetic program, a tryptophan-deficient diet was used to temporarily inhibit juvenile growth in newborn rats for 4 wk. Afterward, microarray analysis showed that the genetic program had been delayed, implying that it is driven by body growth itself rather than age. Taken together, the findings suggest that growth in early life induces progressive down-regulation of a large set of proliferation-stimulating genes, causing organ growth to slow and eventually cease.

Obesity and cancer risk: recent review and evidence.

The prevalence of overweight and obesity is increasing worldwide, and the evidence base for a link between obesity and cancer is growing. In the United States, approximately 85,000 new cancer cases per year are related to obesity. Recent research has found that as the body mass index increases by 5 kg/m2, cancer mortality increases by 10%. Additionally, studies of patients who have had bariatric surgery for weight loss report reductions in cancer incidence and mortality, particularly for women. The goal of this review is to provide an update of recent research, with a focus on epidemiologic studies on the link between obesity and cancer. In addition, we will briefly review hypothesized mechanisms underlying the relationship between obesity and cancer. High priorities for future research involve additional work on the underlying mechanisms, and trials to examine the effect of lifestyle behavior change and weight loss interventions on cancer and intermediate biomarkers.

[Telemedicine in secondary prevention and rehabilitation of stroke during the COVID-19 pandemic]. / Telemedicina en prevención secundaria y rehabilitación del accidente cerebrovascular durante la pandemia por COVID-19.

The COVID-19 pandemic resulted in limited access of post-stroke patients to their usual medical follow-up and rehabilitation. To continue these activities, we adopted a technology that is free and has universal access. We remotely followed 32 patients after discharge from the stroke unit during the mandatory lock-down. This allowed to continue with medical controls, physical therapy and speech pathology treatments. All patients fully complied with medical treatment and self-monitoring of vascular risk factors. Early discontinuation of rehabilitation therapies was identified and immediately compensated with tele-rehabilitation. All expressed their willingness to continue with this treatment modality. This strategy was successful to effectively continue medical follow-up and rehabilitation supervision with the collaboration of families, is an accessible and low-cost technology that could be replicated and used in health institutions that treat neurovascular diseases.

La pandemia COVID-19 limitó el acceso de los pacientes post accidente cerebro vascular a los controles de seguimiento médico y a la rehabilitación, por lo cual decidimos incorporar herramientas tecnológicas gratuitas y accesibles para su continuación. Realizamos seguimiento remoto a 32 pacientes dados de alta en los primeros tres meses del período de aislamiento social preventivo obligatorio con el objetivo de continuar controles médicos, rehabilitación física y fonoaudiológica. El 100% adhirió al tratamiento médico y al auto-monitoreo de factores de riesgo; detectamos en forma temprana la interrupción de las terapias de rehabilitación y mantuvimos la adherencia por medio de tele-rehabilitación. Los 32 pacientes mostraron disponibilidad para seguir con esta modalidad de atención, permitiendo continuar el seguimiento médico y supervisar la rehabilitación con la colaboración de las familias. Es una metodología accesible y de bajo costo que podría ser replicada y utilizada en instituciones de salud que traten enfermedades neurovasculares.

Changes in cell-cycle kinetics responsible for limiting somatic growth in mice.

In mammals, the rate of somatic growth is rapid in early postnatal life but then slows with age, approaching zero as the animal approaches adult body size. To investigate the underlying changes in cell-cycle kinetics, [methyl-H]thymidine and 5'-bromo-2'deoxyuridine were used to double-label proliferating cells in 1-, 2-, and 3-wk-old mice for four weeks. Proliferation of renal tubular epithelial cells and hepatocytes decreased with age. The average cell-cycle time did not increase in liver and increased only 1.7 fold in kidney. The fraction of cells in S-phase that will divide again declined approximately 10 fold with age. Concurrently, average cell area increased approximately 2 fold. The findings suggest that somatic growth deceleration primarily results not from an increase in cell-cycle time but from a decrease in growth fraction (fraction of cells that continue to proliferate). During the deceleration phase, cells appear to reach a proliferative limit and undergo their final cell divisions, staggered over time. Concomitantly, cells enlarge to a greater volume, perhaps because they are relieved of the size constraint imposed by cell division. In conclusion, a decline in growth fraction with age causes somatic growth deceleration and thus sets a fundamental limit on adult body size.

Smaller feedback ERN amplitudes during the BART are associated with a greater family history density of alcohol problems in treatment-naïve alcoholics.

BACKGROUND: Alcoholism is characterized by impaired decision-making (i.e., choosing intoxication in the face of mounting negative consequences). This impairment may involve a reduced brain response to the negative consequences of behavior, which supports an inclination to engage in risky behaviors. The feedback error-related negativity (F-ERN) is hypothesized to reflect the valence attached to the negative consequences of behavior. Performance on the Balloon Analogue Risk Task (BART) measures risk-taking propensity. We recorded F-ERNs during the BART and during a BART simulation, where individuals observed the rewards and consequences of (someone else's) BART performance. METHODS: EEGs were recorded on 22 actively drinking, treatment-naïve alcoholics during the BART and BART simulation. F-ERNs were measured and their association with psychological and alcohol use measures was examined. RESULTS: F-ERNs over fronto-central electrode sites were observed to balloon pops in the BART and BART simulation. F-ERNs during the BART were more than twice the amplitude of F-ERNs during the BART simulation. Smaller F-ERN amplitudes from the BART (but not the BART simulation) were associated with a greater family history density of alcohol problems. CONCLUSION: The results suggest a possible link between the genetic vulnerability toward developing alcoholism and the brain's response to the negative consequences of behavior.

The Cognitive Science of Sketch Worksheets.

Computational modeling of sketch understanding is interesting both scientifically and for creating systems that interact with people more naturally. Scientifically, understanding sketches requires modeling aspects of visual processing, spatial representations, and conceptual knowledge in an integrated way. Software that can understand sketches is starting to be used in classrooms, and it could have a potentially revolutionary impact as the models and technologies become more advanced. This paper looks at one such effort, Sketch Worksheets, which have been used in multiple classroom experiments already, with students ranging from elementary school to college. Sketch Worksheets are a software equivalent of pencil and paper worksheets commonly found in classrooms, but they provide on-the-spot feedback based on what students draw. They are built on the CogSketch platform, which provides qualitative visual and spatial representations and analogical processing based on computational models of human cognition. This paper explores three issues. First, we examine how research from cognitive science and artificial intelligence, combined with the constraints of creating new kinds of educational software, led to the representations and processing in CogSketch. Second, we examine how these capabilities have been used in Sketch Worksheets, drawing upon experiments with fifth-grade students in biology and college students in engineering design and in geoscience. Finally, we examine some open issues in sketch understanding that need to be addressed to better model high-level aspects of vision, and for sketch understanding systems to reach their full potential for supporting education.

Promoting Sketching in Introductory Geoscience Courses: CogSketch Geoscience Worksheets.

Research from cognitive science and geoscience education has shown that sketching can improve spatial thinking skills and facilitate solving spatially complex problems. Yet sketching is rarely implemented in introductory geosciences courses, due to time needed to grade sketches and lack of materials that incorporate cognitive science research. Here, we report a design-centered, collaborative effort, between geoscientists, cognitive scientists, and artificial intelligence (AI) researchers, to characterize spatial learning challenges in geoscience and to design sketch activities that use a sketch-understanding program, CogSketch. We developed 26 CogSketch worksheets that use cognitive science-based principles to scaffold problem solving of spatially complex geoscience problems and report observations of an implementation in an introductory geoscience course where students used CogSketch or human-graded paper worksheets. Overall, this research highlights the principles of interdisciplinary design between cognitive scientists, geoscientists, and AI researchers that can inform the collaborative design process for others aiming to develop effective educational materials.

Electrochemical Coupling of Biomass-Derived Acids: New C8 Platforms for Renewable Polymers and Fuels.

Electrolysis of biomass-derived carbonyl compounds is an alternative to condensation chemistry for supplying products with chain length >C6 for biofuels and renewable materials production. Kolbe coupling of biomass-derived levulinic acid is used to obtain 2,7-octanedione, a new platform molecule only two low process-intensity steps removed from raw biomass. Hydrogenation to 2,7-octanediol provides a chiral secondary diol largely unknown to polymer chemistry, whereas intramolecular aldol condensation followed by hydrogenation yields branched cycloalkanes suitable for use as high-octane, cellulosic gasoline. Analogous electrolysis of an itaconic acid-derived methylsuccinic monoester yields a chiral 2,5-dimethyladipic acid diester, another underutilized monomer owing to lack of availability.

Telemedicina en prevención secundaria y rehabilitación del accidente cerebrovascular durante la pandemia por COVID-19 / Telemedicine in secondary prevention and rehabilitation of stroke during the COVID-19 pandemic

Resumen La pandemia COVID-19 limitó el acceso de los pacientes post accidente cerebro vascular a los controles de seguimiento médico y a la rehabilitación, por lo cual decidimos incorporar herramientas tecnológicas gratuitas y accesibles para su continuación. Realizamos seguimiento remoto a 32 pacientes dados de alta en los primeros tres meses del período de aislamiento social preventivo obligatorio con el objetivo de continuar controles médicos, rehabilitación física y fonoaudiológica. El 100% adhirió al tratamiento médico y al auto-monitoreo de factores de riesgo; detectamos en forma temprana la interrupción de las terapias de rehabilita ción y mantuvimos la adherencia por medio de tele-rehabilitación. Los 32 pacientes mostraron disponibilidad para seguir con esta modalidad de atención, permitiendo continuar el seguimiento médico y supervisar la rehabilitación con la colaboración de las familias. Es una metodología accesible y de bajo costo que podría ser replicada y utilizada en instituciones de salud que traten enfermedades neurovasculares.

Abstract The COVID-19 pandemic resulted in limited access of post-stroke patients to their usual medical follow-up and rehabilitation. To continue these activities, we adopted a technology that is free and has universal access. We remotely followed 32 patients after discharge from the stroke unit during the mandatory lock-down. This allowed to continue with medical controls, physical therapy and speech pathology treatments. All patients fully complied with medical treatment and self-monitoring of vascular risk factors. Early discontinuation of rehabilitation therapies was identified and immediately compensated with tele-rehabilitation. All expressed their willingness to continue with this treatment modality. This strategy was successful to effectively continue medical follow-up and rehabilitation supervision with the collaboration of families, is an accessible and low-cost technology that could be replicated and used in health institutions that treat neurovascular diseases.

Possible Adverse Effects of Repeated Botulinum Toxin A Injections to Decrease Post-Stroke Spasticity in Adults Undergoing Rehabilitation: A Review of the Literature.

Botulinum toxin A (Botox A) is widely prescribed for the management of spasticity due to stroke, and many patients receive repeated injections because the paralyzing effect diminishes after 3 to 4 months. There are many studies that report local complications of Botox A at the injected site. However, little is known about non-local or systemic adverse events with repeated injections. The purpose of this research was to examine published data about adverse effects of repeated Botox A injections. MEDLINE, CINAHL, and PEDro databases were searched for articles that report adverse effects from Botox A injections for reduction of post-stroke spasticity in adults. Based on studies selected for review, the adverse effects from Botox A injections can be classified into local, systemic, and subclinical types. Systemic and subclinical adverse effects are not commonly reported and need further studies. Therapists and the rehabilitation team need to be aware of the potential of these risk factors that may affect the participation of patients undergoing rehabilitation, and therefore other alternatives to these injections may need to be considered.

Valproic acid use during radiation therapy for glioblastoma associated with improved survival.

PURPOSE: Valproic acid (VA) is an antiepileptic drug (AED) and histone deacetylase (HDAC) inhibitor taken by patients with glioblastoma (GB) to manage seizures, and it can modulate the biologic effects of radiation therapy (RT). We investigated whether VA use during RT for GB was associated with overall survival (OS). METHODS AND MATERIALS: Medical records of 544 adults with GB were retrospectively reviewed. Analyses were performed to determine the association of Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA) class, seizure history, and concurrent temozolomide (TMZ) and AED use during RT with OS. RESULTS: Seizures before the end of RT were noted in 217 (40%) patients, and 403 (74%) were taking an AED during RT; 29 (7%) were taking VA. Median OS in patients taking VA was 16.9 months (vs 13.6 months taking another AED, P=.16). Among patients taking an AED during RT, OS was associated with VA (P=.047; hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.27-1.07), and RTOG RPA class (P<.0001; HR, 1.49; 95% CI, 1.37-1.61). Of the 5 most common AEDs, only VA was associated with OS. Median OS of patients receiving VA and TMZ during RT was 23.9 months (vs 15.2 months for patients taking another AED, P=.26). When the analysis was restricted to patients who received concurrent TMZ, VA use was marginally associated with OS (P=.057; HR, 0.54; 95% CI, -0.09 to 1.17), independently of RTOG RPA class and seizure history. CONCLUSIONS: VA use during RT for GB was associated with improved OS, independently of RTOG RPA, seizure history, and concurrent TMZ use. Further studies of treatment that combines HDAC inhibitors and RT are warranted.

The influence of rest period instructions on the default mode network.

The default mode network (DMN) refers to regional brain activity that is greater during rest periods than during attention-demanding tasks; many studies have reported DMN alterations in patient populations. It has also been shown that the DMN is suppressed by scanner background noise (SBN), which is the noise produced by functional magnetic resonance imaging (fMRI). However, it is unclear whether different approaches to "rest" in the noisy MR environment can alter the DMN and constitute a confound in studies investigating the DMN in particular patient populations (e.g., individuals with schizophrenia, Alzheimer's disease). We examined 27 healthy adult volunteers who completed an fMRI experiment with three different instructions for rest: (1) relax and be still, (2) attend to SBN, or (3) ignore SBN. Region of interest analyses were performed to determine the influence of rest period instructions on core regions of the DMN and DMN regions previously reported to be altered in patients with or at risk for Alzheimer's disease or schizophrenia. The dorsal medial prefrontal cortex (dmPFC) exhibited greater activity when specific resting instructions were given (i.e., attend to or ignore SBN) compared to when non-specific resting instructions were given. Condition-related differences in connectivity were also observed between regions of the dmPFC and inferior parietal/posterior superior temporal cortex. We conclude that rest period instructions and SBN levels should be carefully considered for fMRI studies on the DMN, especially studies on clinical populations and groups that may have different approaches to rest, such as first-time research participants and children.