Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of Antihypertensive Treatment on Cerebral Blood Flow in Older Adults: a Systematic Review and Meta-Analysis

Background: In older age, the benefits of antihypertensive treatment (AHT) become less evident, with greater associated risk. Of particular concern is compromising cerebral blood flow (CBF), especially in those with cognitive impairment. Methods: We created a synthesis of the published evidence by searching multiple electronic databases from 1970 to May 2021. Included studies had participants with mean age ≥50 years, hypertension or cognitive impairment, and assessed CBF before and after initiating AHT. Two authors independently determined eligibility and extracted data. Study quality was assessed using The Risk of Bias in Nonrandomized Studies of Interventions tool. We summarized study characteristics (qualitative synthesis) and performed random-effects meta-analyses (quantitative synthesis). Results: Thirty-two studies (total n=1306) were included, of which 23 were eligible for meta-analysis. In line with the qualitative synthesis, the meta-analysis indicated no effect of AHT initiation on CBF (standardized mean difference, 0.08 [95% CI, −0.07 to 0.22]; P=0.31, I2=42%). This was consistent across subgroups of acute versus chronic AHT, drug class, study design, and CBF measurement. Subgroups by age demonstrated an increase in CBF after AHT in those aged >70 years (standardized mean difference, 4.15 [95% CI, 0.16–8.15]; P=0.04, I2=42%), but not in those aged 50 to 65 and 65 to 70 years (standardized mean difference, 0.18 [95% CI,−2.02 to 2.38]; P=0.87, I2=49%; standardized mean difference, 1.22 [95% CI, −0.45 to 2.88]; P=0.15, I2=68%). Overall, risk of bias was moderate-to-high and quality of evidence (Grading of Recommendations Assessment, Development and Evaluation) was very low, reflecting the observational nature of the data. Conclusions: Accepting the observed limitations, current evidence does not suggest a harmful effect of AHT on CBF. Concerns over CBF should not preclude treatment of hypertension.
Unconscious Influences on “Free Will” Movement Initiation: Slow-wave Brain Stimulation and the Readiness Potential

Abstract A central objective in the study of volition has been to identify how changes in neural activity relate to voluntary—“free will”—movement. The readiness potential (RP) is observed in the EEG as a slow-building signal that precedes action onset. Many consider the RP as a marker of an underlying preparatory process for initiating voluntary movement. However, the RP may emerge from ongoing slow-wave brain oscillations that influence the timing of movement initiation in a phase-dependent manner. Transcranial alternating current stimulation (tACS) enables brain oscillations to be entrained at the frequency of stimulation. We delivered tACS at a slow-wave frequency over frontocentral motor areas while participants (n = 30) performed a simple, self-paced button press task. During the active tACS condition, participants showed a tendency to initiate actions in the phase of the tACS cycle that corresponded to increased negative potentials across the frontocentral motor region. Comparisons of premovement EEG activity observed over frontocentral and central scalp electrodes showed earlier onset and increased amplitude of RPs from active stimulation compared with sham stimulation. This suggests that movement-related activity in the brain can be modulated by the delivery of weak, nonconsciously perceptible alternating currents over frontocentral motor regions. We present novel findings that support existing theories, which suggest the timing of voluntary movement is influenced by the phase of slow-changing oscillating brain states.
Starter feed for carnivorous species as a practical replacement of bloodworms for a vertebrate model organism in ageing, turquoise killifish Nothobranchius furzeri.

The absence of a controlled diet is unfortunate in a promising model organism for ageing - the turquoise killifish (Nothobranchius furzeri Jubb, 1971). Currently captive N. furzeri are fed bloodworm but it is not known whether this is an optimal diet. Replacing bloodworm with a practical dry feed would reduce diet variability. In the present study, we estimated the nutritional value of the diet ingested by wild fish and determined the fish-body amino acid profile as a proxy for their nutritional requirements. We compared the performance of fish fed four commercial feeds containing 46%-64% protein to that achieved with bloodworm and that of wild fish. Wild fish target a high protein (60%) diet and this is supported by their superior performance on high protein diets in captivity. In contrast, feeds for omnivores led to slower growth, lower fecundity and unnatural liver size. In comparison to wild fish, a bloodworm diet led to lower body condition, overfeeding, and male liver enlargement. Out of the four dry feeds tested, the fish fed Aller matched wild fish in body condition and liver size and was comparable to bloodworm in terms of growth and fecundity. A starter feed for carnivorous species appears to be a practical replacement for bloodworm for N. furzeri. The use of dry feeds improved performance in comparison to bloodworms and thus may contribute to reducing response variability and improving research reproducibility in N. furzeri research. This article is protected by copyright. All rights reserved.
Understanding Discussions of Sexual Assault in Young Women on a Peer Support Mental Health App: A Content Analysis

Trauma narratives may have been influenced by the Me Too movement, with thousands of individuals disclosing sexual violence stories online. Youth, the largest demographic of online users, may prefer the anonymity of the Internet to discuss experiences of sexual assault. Understanding the ways that young women, especially those experiencing mental health difficulties, discuss their experiences is important as they are at higher risk of revictimization and continued poor mental health. We searched for terms related to acts of sexual assault on a mental health peer-support app, TalkLife, and compared the number of posts during the initial wave of the Me Too movement (October 2017–March 2018) to the same time period in the previous year (October 2016–March 2017). We found a significant increase in posts related to sexual assault of 49.7% between the Pre and Post Me Too time periods (p < .001), controlling for a general increase in posts. A content analysis of 700 randomly selected posts found that a substantial number of young women used TalkLife to discuss their experiences of sexual assault, and these self-disclosures were mostly hopeless or depressing in tone. Additionally, neither the nature nor the number of self-disclosures varied across time points. The negative tone of the self-disclosures in the current study is worrying because the way women talk about their trauma can shape how they understand it, which could lead to negative self-appraisal and continued mental health difficulties. Online spaces have the potential to support young women and facilitate help-seeking, but we must be attentive to how they are used.
A qualitative study showing that a telecare tool can have benefits before and during the initial hearing assessment appointment

Abstract Objective To examine patient and audiologist experiences and perspectives of using a patient-centred telecare tool, the Ida Institute’s Why Improve My Hearing? (WIMH) Tool, before and during the initial hearing assessment appointment. Design A qualitative study comprising individual semi-structured interviews using a maximum variation sampling strategy. The data were analysed using an established thematic analysis technique. Study sample Fifteen participants, including ten patients (i.e. adults with hearing loss) and five audiologists, were recruited from Adult Audiology Services within the United Kingdom’s publicly-funded National Health Service (NHS). Results Three themes described the impact of using the WIMH Tool. Theme 1 (i.e. enhanced preparation before the appointment): the Tool helps patients to better understand and accept their hearing difficulties in advance of their first appointment. Theme 2 (i.e. enriched discussion during the appointment): the tool can enhance patient-centred communication, as well as the efficiency of the appointment. Theme 3 (i.e. varied impact on outcomes following the appointment): the Tool can improve patient motivation, readiness, and involvement in decision-making, though it may have limited impact on additional outcomes, such as adherence. Conclusion The WIMH Tool can be successfully implemented in audiological practice, resulting in benefits before and during the initial hearing assessment appointment.
Stromal oncostatin M cytokine promotes breast cancer progression by reprogramming the tumor microenvironment

The tumor microenvironment (TME) is reprogrammed by cancer cells and participates in all stages of tumor progression. The contribution of stromal cells to the reprogramming of the TME is not well understood. Here, we provide evidence of the role of the cytokine oncostatin M (OSM) as central node for multicellular interactions between immune and nonimmune stromal cells and the epithelial cancer cell compartment. OSM receptor (OSMR) deletion in a multistage breast cancer model halted tumor progression. We ascribed causality to the stromal function of the OSM axis by demonstrating reduced tumor burden of syngeneic tumors implanted in mice lacking OSMR. Single-cell and bioinformatic analysis of murine and human breast tumors revealed that OSM expression was restricted to myeloid cells, whereas OSMR was detected predominantly in fibroblasts and, to a lower extent, cancer cells. Myeloid-derived OSM reprogrammed fibroblasts to a more contractile and tumorigenic phenotype and elicited the secretion of VEGF and proinflammatory chemokines CXCL1 and CXCL16, leading to increased myeloid cell recruitment. Collectively, our data support the notion that the stromal OSM/OSMR axis reprograms the immune and nonimmune microenvironment and plays a key role in breast cancer progression.
Bacteriophage protein Gp46 is a cross-species inhibitor of nucleoid-associated HU proteins

Significance Histone-like protein from Escherichia coli strain U93 (HU) protein is the most abundant nucleoid-associated protein in bacteria, which plays a fundamental role in chromosomal compaction and organization. It is essential for most bacteria as well as Apicomplexans, thus an important target for the development of antimicrobial and antimalaria drugs. We report Gp46 as a phage protein HU inhibitor. It inhibits HU of Bacillus subtilis by occupying its DNA binding site, thus preventing chromosome segregation during cell division. As key residues for the interaction are highly conserved, Gp46 interacts with HUs of a broad range of pathogens, including many pathogenic bacteria and Apicomplexan parasites like Plasmodium falciparum. Thus, this cross-species property could benefit antibiotic and antimalaria drug development that targets HU.
Fast-track revision hip arthroplasty: a multicenter cohort study on 1,345 elective aseptic major component revision hip arthroplasties

Background and purpose Data on application of fast-track/enhanced recovery protocols in revision hip arthroplasty (R-THA) surgery is scarce. We report length of stay (LOS), risk of LOS > 5 days, and readmission ≤ 90 days after revision hip arthroplasty in centers with a well-established fast-track protocol in both primary and revision procedures. Patients and methods This is an observational cohort study from the Centre for Fast-track Hip and Knee Replacement and the Danish Hip Arthroplasty Register. Consecutive elective aseptic major component revision hip arthroplasties from 6 dedicated fast-track centers from 2010 to 2018 were included. Results 1,345 R-THAs were analyzed, including 23% total revisions, 52% acetabular component revisions, and 25% femoral component revisions. Mean age was 70 years (SD 12) and 61% were female. Median LOS was 3 days (interquartile range [IQR] 2–6), decreasing from median 6 (IQR 3–10) days in 2010 to 2 (IQR 1–4) days in 2018. The 90-day readmission rate was 20%, but showed a fluctuating and increasing trend from 13% in 2010 to 28% in 2018. Risk factors for LOS > 5 days and readmission were use of walking aid, preoperative hemoglobin ≤ 13 g/dL, pharmacological treated psychiatric disorder, age ≥ 80 years, age 70–79 years (only LOS > 5 days), cardiac disease (only LOS > 5 days), pulmonary disease (only readmission), BMI ≥ 35 (only LOS > 5 days) and ≥ 1 previous revision (only LOS > 5 days). Interpretation LOS decreased to median 2 days at the end of the study period, but the 90 days readmission risk remained high (> 20%). Several risk factors for postoperative complications were identified, suggesting that at-risk patients should be treated using an extended fast-track/enhanced recovery protocol focusing on preoperative optimization and postoperative monitoring as well as surgical techniques to reduce hip dislocations.
Hiring women into senior leadership positions is associated with a reduction in gender stereotypes in organizational language

Significance Gender inequality has been deemed the “greatest human rights challenge of our time” by the United Nations, and scholars across numerous disciplines agree that gender stereotypes represent a primary way by which this inequality is maintained. Yet changing stereotypes in a systemic, enduring way is extremely difficult. This is at least in part because stereotypes are transmitted and perpetuated through the language societies and organizations use to describe women, especially those in leadership roles. Here, we show that hiring women into leadership positions is associated with organizations characterizing women in more leadership-congruent, agentic ways. This shift mitigates a critical barrier to women’s progression in organizations and society: the incongruence of what it means to be a woman and a leader.
Emotion Downregulation Targets Interoceptive Brain Regions While Emotion Upregulation Targets Other Affective Brain Regions

Researchers generally agree that when upregulating and downregulating emotion, control regions in the prefrontal cortex turn up or down activity in affect-generating brain areas. However, the “affective dial hypothesis” that turning up and down emotions produces opposite effects in the same affect-generating regions is untested. We tested this hypothesis by examining the overlap between the regions activated during upregulation and those deactivated during downregulation in 54 male and 51 female humans. We found that upregulation and downregulation both recruit regulatory regions, such as the inferior frontal gyrus and dorsal anterior cingulate gyrus, but act on distinct affect-generating regions. Upregulation increased activity in regions associated with emotional experience, such as the amygdala, anterior insula, striatum, and anterior cingulate gyrus as well as in regions associated with sympathetic vascular activity, such as periventricular white matter, while downregulation decreased activity in regions receiving interoceptive input, such as the posterior insula and postcentral gyrus. Nevertheless, participants' subjective sense of emotional intensity was associated with activity in overlapping brain regions (dorsal anterior cingulate, insula, thalamus, and frontal pole) across upregulation and downregulation. These findings indicate that upregulation and downregulation rely on overlapping brain regions to control and assess emotions but target different affect-generating brain regions. SIGNIFICANCE STATEMENT Many contexts require modulating one's own emotions. Identifying the brain areas implementing these regulatory processes should advance understanding emotional disorders and designing potential interventions. The emotion regulation field has an implicit assumption we call the affective dial hypothesis: both emotion upregulation and downregulation modulate the same emotion-generating brain areas. Countering the hypothesis, our findings indicate that up- and down-modulating emotions target different brain areas. Thus, the mechanisms underlying emotion regulation might differ more than previously appreciated for upregulation versus downregulation. In addition to their theoretical importance, these findings are critical for researchers attempting to target activity in particular brain regions during an emotion regulation intervention.
Love, sex, and commitment: relationship choices and trajectories among unmarried youth in India

Abstract There is limited research in India to understand young people's decision-making processes about intimate relationships before marriage. This paper, adopting a life course perspective, explains relationship choices and diachronic trajectories of relationships from adolescence to young adulthood. Retrospective data were collected from 1240 never married 20–29-year-old men and women living in Pune using a relationships history calendar. All the relationships from 10 years of age onwards were plotted on the calendar, and information on predictor variables was collected through structured questionnaires. Data were analysed using descriptive statistics. Sequence analysis approach was used to identify different typologies. Overall, 76% of the participants reported having at least one relationship. More women compared to men (84% vs 70%) ever had a relationship. The median age of starting the first relationship was 17 years for women and 18 for men. Different relationship types were reported, such as “serious”, casual, “friends with benefit”, and “exploring”. The level of emotional involvement, commitment, and physical intimacy significantly differed in different relationship types with significant gender differences. Four typologies of relationships were observed, labelled as (1) Commitment–No sex (N = 187); (2) Commitment–Sex-Some exploration (N = 189); (3) No commitment–Exploration (N = 281), and (4) No relationship (N = 583). Compared to men, women were more likely to follow the trajectory of “Commitment-No sex” (RR 2.13, CI 1.5–3.03). Family environment was significantly related to young people's relationship choices. The findings strongly suggest the need to adopt a developmental perspective towards intimate relationships to understand and address the vulnerabilities of young people across the life course.
Craniocervical Instability in Ehlers-Danlos Syndrome—A Systematic Review of Diagnostic and Surgical Treatment Criteria

Study Design Systematic review. Objective Ehlers-Danlos Syndrome (EDS) comprises a spectrum of connective tissue disorders, which may be associated with cranio-cervical instability (CCI). There is a lack of consensus on diagnostic imaging parameters, indications, and outcomes of surgical treatment. Methods This systematic review analyses the literature on diagnostic methods and/or criteria for CCI, screening the databases Ovid Medline, Embase, Cochrane Library, and PubMed. Articles were included based on the PRISMA guidelines and assessed using the Newcastle-Ottawa Quality Assessment Scale (NOS) and according to their evidence level. Results Sixteen articles, including 78 surgical patients, met the inclusion criteria. The main diagnostic measures for CCI were dynamic x-rays and CT imaging. Ten different radiographic parameters were reported, of which 4 were the most frequently applied for surgical decision-making: the clivo-axial angle (CXA), the Harris measurement, the Grabb–Mapstone–Oakes measurement, and the angular displacement of C1 to C2. The evidence level ranged between III and V and the article quality between 4 and 8 out of 9 stars on the NOS Scale. Conclusions There is a lack of high quality, prospective evidence regarding the evaluation of suspected CCI in patients with EDS. Based on our systematic review, we recommend that the CXA, Harris measurement, Grabb–Mapstone–Oakes measurement, and the angular displacement of C1 to C2 be used to evaluate suspected CCI in EDS patients. Surgical fixation of suspected CCI should only be performed in cases with clear radiographic presence of instability and concordant symptoms/signs. Consensus-based guidelines and care pathways are required.
Environmental enrichment enhances patterning and remodeling of synaptic nanoarchitecture as revealed by STED nanoscopy

Synaptic plasticity underlies long-lasting structural and functional changes to brain circuitry and its experience-dependent remodeling can be fundamentally enhanced by environmental enrichment. It is unknown, however, whether and how environmental enrichment alters the morphology and dynamics of individual synapses. Here, we present a virtually crosstalk free, two-color in vivo STED microscope to simultaneously superresolve the dynamics of endogenous PSD95 of the post-synaptic density and spine geometry. With environmental enrichment, the size distributions of PSD95 and spine head sizes were sharper than in controls, indicating that synaptic strength is set more precisely with environmental enrichment. Spine head geometry and PSD95 assemblies were highly dynamic but their changes correlated only mildly. With environmental enrichment, the topography of the PSD95 nanoorganization was more dynamic; changes in size were smaller than in mice housed in standard cages and depended linearly on their original size. Thus, two-color in vivo time-lapse imaging of synaptic nanoorganization uncovers a unique synaptic nanoplasticity associated with the enhanced learning capabilities under environmental enrichment.
Bottom-up and top-down modulation of route selection in imitation

ABSTRACT The cognitive system selects the most appropriate action imitative process: a semantic process – relying on long-term memory representations for known actions, and low-level visuomotor transformations for unknown actions. These two processes work in parallel; however, how context regularities and cognitive control modulate them is unclear. In this study, process selection was triggered contextually by presenting mixed known and new actions in predictable or unpredictable lists, while a cue on the forthcoming action triggered top-down control. Known were imitated faster than the new actions in the predictable lists only. Accuracy was higher and reaction times faster in the uncued conditions, and the predictable faster than the unpredictable list in the uncued condition only. In the latter condition, contextual factors modulate process selection, as participants use statistical regularities to perform the task at best. With the cue, the cognitive system tries to control response selection, resulting in more errors and longer reaction times.