Miracle-dz/UniFAR-FTUs huggingface dataset:
Real-Time Functional Connectivity-Informed Neurofeedback of Amygdala-Frontal Pathways Reduces Anxiety

Background: Deficient emotion regulation and exaggerated anxiety represent a major transdiagnostic psychopathological marker. On the neural level these deficits have been closely linked to impaired, yet treatment-sensitive, prefrontal regulatory control over the amygdala. Gaining direct control over these pathways could therefore provide an innovative and promising intervention to regulate exaggerated anxiety. To this end the current proof-of-concept study evaluated the feasibility, functional relevance and maintenance of a novel connectivity-informed real-time fMRI neurofeedback training. Methods: In a randomized crossover sham-controlled design, 26 healthy subjects with high anxiety underwent real-time fMRI-guided neurofeedback training to enhance connectivity between the ventrolateral prefrontal cortex (vlPFC) and the amygdala (target pathway) during threat exposure. Maintenance of regulatory control was assessed after 3 days and in the absence of feedback. Training-induced changes in functional connectivity of the target pathway and anxiety ratings served as primary outcomes. Results: Training of the target, yet not the sham control, pathway significantly increased amygdala-vlPFC connectivity and decreased levels of anxiety. Stronger connectivity increases were significantly associated with higher anxiety reduction on the group level. At the follow-up, volitional control over the target pathway was maintained in the absence of feedback. Conclusions: The present results demonstrate for the first time that successful self-regulation of amygdala-prefrontal top-down regulatory circuits may represent a novel intervention to control anxiety. As such, the present findings underscore both the critical contribution of amygdala-prefrontal circuits to emotion regulation and the therapeutic potential of connectivity-informed real-time neurofeedback.
Genetic Structure and Eco-Geographical Differentiation of Lancea tibetica in the Qinghai-Tibetan Plateau

The uplift of the Qinghai-Tibetan Plateau (QTP) had a profound impact on the plant speciation rate and genetic diversity. High genetic diversity ensures that species can survive and adapt in the face of geographical and environmental changes. The Tanggula Mountains, located in the central of the QTP, have unique geographical significance. The aim of this study was to investigate the effect of the Tanggula Mountains as a geographical barrier on plant genetic diversity and structure by using Lancea tibetica. A total of 456 individuals from 31 populations were analyzed using eight pairs of microsatellite makers. The total number of alleles was 55 and the number per locus ranged from 3 to 11 with an average of 6.875. The polymorphism information content (PIC) values ranged from 0.2693 to 0.7761 with an average of 0.4378 indicating that the eight microsatellite makers were efficient for distinguishing genotypes. Furthermore, the observed heterozygosity (Ho), the expected heterozygosity (He), and the Shannon information index (I) were 0.5277, 0.4949, and 0.9394, respectively, which indicated a high level of genetic diversity. We detected high genetic differentiation among all sampling sites and restricted gene flow among populations. Bayesian-based cluster analysis (STRUCTURE), principal coordinates analysis (PCoA), and Neighbor-Joining (NJ) cluster analysis based on microsatellite markers grouped the populations into two clusters: the southern branch and the northern branch. The analysis also detected genetic barriers and restricted gene flow between the two groups separated by the Tanggula Mountains. This study indicates that the geographical isolation of the Tanggula Mountains restricted the genetic connection and the distinct niches on the two sides of the mountains increased the intraspecific divergence of the plants.
Hydrodynamics of frontal striking in aquatic snakes: drag, added mass, and the possible consequences for prey capture success

Transient locomotion under water is highly constrained by drag and added mass, yet some aquatic snakes catch their prey using a fast forward acceleration, with the mouth opened. These aquatic snakes show a convergence of their head shape in comparison with closely related species that do not forage under water. As both drag and added mass are related to some extent to the shape of the moving object, we explored how shape impacts the hydrodynamic forces applied to the head of a snake during a prey capture event. We compared two 3D-printed heads representing typical shapes of aquatically-foraging and non-aquatically-foraging snakes, and frontal strike kinematics based on in vivo observations. By using direct force measurements, we calculated the drag and added mass coefficient of the two models. Our results show that both drag and added mass are reduced in aquatic snakes. The drag coefficient of the aquatic model is 0.24, which is almost two times smaller than the non-aquatic model. The added mass coefficient of the aquatic model is 0.15 versus 0.24 for the non-aquatic model, showing that the convergence of head shape in aquatically foraging snakes is associated with a hydrodynamic advantage during frontal striking. The vorticity field measurements with particle image velocimetry show that a less intense recirculation bubble behind the jaw of the aquatic model, compared to the non-aquatic model, might be the basis of this advantage.
Examining the associations between children's receptive language skills and developmental domains in the United States and Turkey

Abstract This study examined the relations between receptive language development and other developmental domains of preschoolers from low-income families, through an inter-cultural perspective involving the United States and Turkey. A total of 471 children and their caregivers participated in Turkey, while 287 participated in the United States. Children's development was assessed using the Ages and Stages Questionnaire for both samples. Different versions of the Peabody Picture Vocabulary Test were used for Turkish and US samples, to measure receptive language development. Results revealed similar patterns, with some differences, between the two countries. Receptive language predicted only communication and personal–social scales in the Turkish sample, while the US children's receptive language skills were associated with communication, problem solving, personal–social, and fine and gross motor development scales. These results were discussed in the context of each country, and the comparative conclusions contribute to the extant literature by illustrating the importance of language for three domains.
Sunitinib in patients with pancreatic neuroendocrine tumors: update of safety data.

AIM To describe the long-term safety of sunitinib in patients with progressive, well-differentiated, advanced/metastatic pancreatic neuroendocrine tumors. PATIENTS & METHODS Sunitinib- and placebo-treated patients from the Phase III study continued to receive sunitinib (37.5 mg on a continuous daily-dosing regimen) in two open-label extension studies. RESULTS Median (range) treatment exposure: 30.2 (0.7-269.4) and 87.1 (3.9-319.4) weeks for medium-term (n = 41) and long-term-treated (n = 61) populations, respectively. All patients experienced ≥1 adverse event (AE); 47 (45.6%) reported serious AEs. Common all-causality AEs: diarrhea (63.1%); neutropenia (43.7%); abdominal pain (40.8%). Fifteen (14.6%) patients discontinued treatment due to treatment-related AEs. CONCLUSION The safety of extended sunitinib treatment was consistent with the known safety profile of sunitinib in pancreatic neuroendocrine tumors.
Histopathology of diffusion imaging abnormalities in cerebral amyloid angiopathy

Objective We sought to determine the underlying mechanism for altered white matter diffusion tensor imaging (DTI) measures at the histopathologic level in patients with cerebral amyloid angiopathy (CAA). Methods Formalin-fixed intact hemispheres from 9 CAA cases and 2 elderly controls were scanned at 3-tesla MRI, including a diffusion-weighted sequence. DTI measures (i.e., fractional anisotropy [FA] and mean diffusivity [MD]) and histopathology measures were obtained from 2 tracts: the anterior thalamic radiation and inferior longitudinal fasciculus. Results FA was reduced in both tracts and MD was increased in cases with CAA compared to controls. Regional FA was significantly correlated with tissue rarefaction, myelin density, axonal density, and white matter microinfarcts. MD correlated significantly with tissue rarefaction, myelin density, and white matter microinfarcts, but not axonal density. FA and MD did not correlate with oligodendrocytes, astrocytes, or gliosis. Multivariate analysis revealed that tissue rarefaction (β = −0.32 ± 0.12, p = 0.009) and axonal density (β = 0.25 ± 0.12, p = 0.04) were both independently associated with FA, whereas myelin density was independently associated with MD (β = −0.32 ± 0.12, p = 0.013). Finally, we found an association between increased MD in the frontal white matter and CAA severity in the frontal cortex (p = 0.035). Conclusions These results suggest that overall tissue loss, and in particular axonal and myelin loss, are major components underlying CAA-related alterations in DTI properties observed in living patients. The findings allow for a more mechanistic interpretation of DTI parameters in small vessel disease and for mechanism-based selection of candidate treatments to prevent vascular cognitive impairment.
Ultrastructural Changes and Putative Phage Particles Observed in Sweet Orange Leaves Infected with 'Candidatus Liberibacter asiaticus'.

Huanglongbing (HLB), also known as citrus greening, is currently the most destructive citrus disease. Anatomical analyses of HLB-affected sweet orange were carried out by light and electron microscopy. As compared with healthy citrus, the phloem plasmodesmata were plugged with callose, and in some samples the phloem was collapsed. Chloroplast structures were deformed. Prophage sequences occupy a significant portion of the genome of 'Candidatus Liberibacter asiaticus' and have been used to distinguish strains from Yunnan and Guangdong provinces in China and Florida. Interestingly, a large number of possible putative phage particles were observed attached on the surface of 'Ca. L. asiaticus' cells in plants inoculated with strain FJ3 from Fujian Province, China. Phage particles have been observed previously only in periwinkle plants artificially inoculated in Florida with 'Ca. L. asiaticus' that carried the SC1-type prophage. PCR assays verified the presence of the SC1-type prophage sequences previously described from this bacterium in Florida in the FJ3 isolate. This is the first time that suspected phage particles have been observed in sweet orange trees infected with 'Ca. L. asiaticus. '
Flunarizine as prophylaxis for episodic migraine: a systematic review with meta-analysis

Abstract Based on few clinical trials, flunarizine is considered a first-line prophylactic treatment for migraine in several guidelines. In this meta-analysis, we examined the pooled evidence for its effectiveness, tolerability, and safety. Prospective randomized controlled trials of flunarizine as a prophylaxis against migraine were identified from a systematic literature search, and risk of bias was assessed for all included studies. Reduction in mean attack frequency was estimated by calculating the mean difference (MD), and a series of secondary outcomes—including adverse events (AEs)—were also analyzed. The database search yielded 879 unique records. Twenty-five studies were included in data synthesis. We scored 31/175 risk of bias items as “high,” with attrition as the most frequent bias. A pooled analysis estimated that flunarizine reduces the headache frequency by 0.4 attacks per 4 weeks compared with placebo (5 trials, 249 participants: MD −0.44; 95% confidence interval −0.61 to −0.26). Analysis also revealed that the effectiveness of flunarizine prophylaxis is comparable with that of propranolol (7 trials, 1151 participants, MD −0.08; 95% confidence interval −0.34 to 0.18). Flunarizine also seems to be effective in children. The most frequent AEs were sedation and weight increase. Meta-analyses were robust and homogenous, although several of the included trials potentially suffered from high risk of bias. Unfortunately, reporting of AEs was inconsistent and limited. In conclusion, pooled analysis of data from partially outdated trials shows that 10-mg flunarizine per day is effective and well tolerated in treating episodic migraine—supporting current guideline recommendations.
Chewing the Fat: The Conserved Ability of DNA Viruses to Hijack Cellular Lipid Metabolism

Viruses manipulate numerous host factors and cellular pathways to facilitate the replication of viral genomes and the production of infectious progeny. One way in which viruses interact with cells is through the utilization and exploitation of the host lipid metabolism. While it is likely that most—if not all—viruses require lipids or intermediates of lipid synthesis to replicate, many viruses also actively induce lipid metabolic pathways to sustain a favorable replication environment. From the formation of membranous replication compartments, to the generation of ATP or protein modifications, viruses exhibit differing requirements for host lipids. Thus, while the exploitation of lipid metabolism is a common replication strategy, diverse viruses employ a plethora of mechanisms to co-opt these critical cellular pathways. Here, we review recent literature regarding the exploitation of host lipids and lipid metabolism specifically by DNA viruses. Importantly, furthering the understanding of the viral requirements for host lipids may offer new targets for antiviral therapeutics and provide opportunities to repurpose the numerous FDA-approved compounds targeting lipid metabolic pathways as antiviral agents.
Accelerated Degeneration of a Bovine Pericardial Bioprosthetic Aortic Valve in Children and Young Adults

Background— Experience with aortic valve replacement (AVR) with current-generation pericardial bioprostheses in young patients is limited. The death of a child with accelerated bioprosthetic aortic stenosis prompted enhanced surveillance of all such patients at our institution. Methods and Results— We reviewed records of 27 patients who had undergone AVR (median follow-up, 13.7 months) with a bovine pericardial bioprosthesis at ⩽30 years of age. In the Mitroflow LXA valve group (n=15), freedom from valve failure was 100% at 1 year, 53% (95% confidence interval, 12–82) at 2 years, and 18% (95% confidence interval, 1–53) at 3 years. No Magna/Magna Ease valves (n=12) failed by 3 years. Among valve failure patients, median age at AVR was 12 years (range, 10–21 years). Life-threatening prosthetic aortic stenosis was detected at a median of 6 months after prior echocardiograms showing mild or less gradients. Patients with Mitroflow LXA compared with Magna/Magna Ease valves were smaller (median body surface area, 1.42 versus 1.93 m2; P=0.002) and younger (median age, 13.0 versus 20.9 years; P=0.02) at AVR. Pathology demonstrated diffuse intrinsic leaflet calcification, not associated with inflammation or infection, and virtually immobile leaflets in closed position. Conclusions— Young patients undergoing AVR with Mitroflow LXA pericardial valves are at high risk for rapid progression from mild or less to severe aortic stenosis over months, highlighting their need for heightened echocardiographic surveillance and suggesting that this aortic bioprosthesis should not be implanted in the young. Current data are insufficient to assess the safety of AVR with other pericardial bioprostheses in children and the youngest adults.
Extracellular Vesicles as Transmitters of Hypoxia Tolerance in Solid Cancers

Tumour hypoxia is a common feature of solid tumours that contributes to poor prognosis after treatment. This is mainly due to increased resistance of hypoxic cells to radio- and chemotherapy and the association of hypoxic cells with increased metastasis development. It is therefore not surprising that an increased hypoxic tumour fraction is associated with poor patient survival. The extent of hypoxia within a tumour is influenced by the tolerance of individual tumor cells to hypoxia, a feature that differs considerably between tumors. High numbers of hypoxic cells may, therefore, be a direct consequence of enhanced cellular capability inactivation of hypoxia tolerance mechanisms. These include HIF-1α signaling, the unfolded protein response (UPR) and autophagy to prevent hypoxia-induced cell death. Recent evidence shows hypoxia tolerance can be modulated by distant cells that have experienced episodes of hypoxia and is mediated by the systemic release of factors, such as extracellular vesicles (EV). In this review, the evidence for transfer of a hypoxia tolerance phenotype between tumour cells via EV is discussed. In particular, proteins, mRNA and microRNA enriched in EV, derived from hypoxic cells, that impact HIF-1α-, UPR-, angiogenesis- and autophagy signalling cascades are listed.
Perinatal depression care pathway for obstetric settings

Abstract Perinatal depression is common and can have deleterious effects on mothers, infants, children, partners, and families. Despite this, few women who screen positive for depression receive psychiatric treatment. A comprehensive perinatal depression care pathway includes: (1) screening, (2) assessment, (3) triage and referral, (4) treatment access, (5) treatment initiation, (6) symptom monitoring, and (7) adaptation of treatment based on measurement until symptoms remit. This depression care pathway provides a scaffold on which to frame the challenges encountered when, and the opportunities that exist for, addressing depression in obstetric settings. Comprehensive interventions that address each step on the care pathway are needed to support obstetric practices in providing high-quality, evidence-based, effective treatment including pro-active follow-up for depression management. Despite recent attention being brought to, and significant progress in the field of maternal mental health, gaps in care persist. Ultimately, depression care needs to be fully integrated into obstetric care. Additionally, more targeted maternal mental health support and structure are needed for integration to occur and ultimately be optimized. Specific areas requiring more attention include consistency of screening, evaluation of patients with a positive depression screen for bipolar disorder, anxiety or substance use disorders, and monitoring of symptom improvement.
The Multimodal Nature of High-Intensity Functional Training: Potential Applications to Improve Sport Performance

Training for sports performance requires the development of multiple fitness components within the same program. In this context, training strategies that have the potential to concomitantly enhance metabolic and musculoskeletal fitness are of great value for athletes and coaches. The purpose of this manuscript is to review the current studies on high-intensity functional training (HIFT) and to assess how HIFT could be utilized in order to improve sport-specific performance. Studies on untrained and recreationally-active participants have led to positive results on aerobic power and anaerobic capacity, and muscular endurance, while results on muscular strength and power are less clear. Still, HIFT sessions can elicit high levels of metabolic stress and resistance training exercises are prescribed with parameters that can lead to improvements in muscular endurance, hypertrophy, strength, and power. As similar training interventions have been shown to be effective in the athletic population, it is possible that HIFT could be a time-efficient training intervention that can positively impact athletes’ performances. While the potential for improvements in fitness and performance with HIFT is promising, there is a clear need for controlled studies that employ this training strategy in athletes in order to assess its effectiveness in this population.
Meta-Analysis of Quantitative Trait Loci Associated with Seedling-Stage Salt Tolerance in Rice (Oryza sativa L.)

Soil and water salinity is one of the major abiotic stresses that reduce growth and productivity in major food crops including rice. The lack of congruence of salt tolerance quantitative trait loci (QTLs) in multiple genetic backgrounds and multiple environments is a major hindrance for undertaking marker-assisted selection (MAS). A genome-wide meta-analysis of QTLs controlling seedling-stage salt tolerance was conducted in rice using QTL information from 12 studies. Using a consensus map, 11 meta-QTLs for three traits with smaller confidence intervals were localized on chromosomes 1 and 2. The phenotypic variance of 3 meta-QTLs was ≥20%. Based on phenotyping of 56 diverse genotypes and breeding lines, six salt-tolerant genotypes (Bharathy, I Kung Ban 4-2 Mutant, Langmanbi, Fatehpur 3, CT-329, and IARI 5823) were identified. The perusal of the meta-QTL regions revealed several candidate genes associated with salt-tolerance attributes. The lack of association between meta-QTL linked markers and the level of salt tolerance could be due to the low resolution of meta-QTL regions and the genetic complexity of salt tolerance. The meta-QTLs identified in this study will be useful not only for MAS and pyramiding, but will also accelerate the fine mapping and cloning of candidate genes associated with salt-tolerance mechanisms in rice.
An open source autocorrelation-based method for fetal heart rate estimation from one-dimensional Doppler ultrasound

Objective: Open research on fetal heart rate (FHR) estimation is relatively rare, and evidence for the utility of metrics derived from Doppler ultrasound devices has historically remained hidden in the proprietary documentation of commercial entities, thereby inhibiting its assessment and improvement. Nevertheless, recent studies have attempted to improve FHR estimation; however, these methods were developed and tested using datasets composed of few subjects and are therefore unlikely to be generalizable on a population level. The work presented here introduces a reproducible and generalizable autocorrelation (AC)-based method for FHR estimation from one-dimensional Doppler ultrasound (1D-DUS) signals. Approach: Simultaneous fetal electrocardiogram (fECG) and 1D-DUS signals generated by a hand-held Doppler transducer in a fixed position were captured by trained healthcare workers in a European hospital. The fECG QRS complexes were identified using a previously published fECG extraction algorithm and were then over-read to ensure accuracy. An AC-based method to estimate FHR was then developed on this data, using a total of 721 1D-DUS segments, each 3.75 s long, and parameters were tuned with Bayesian optimization. The trained FHR estimator was tested on two additional (independent) hand-annotated Doppler-only datasets recorded with the same device but on different populations: one composed of 3938 segments (from 99 fetuses) acquired in rural Guatemala, and another composed of 894 segments (from 17 fetuses) recorded in a hospital in the UK. Main results: The proposed AC-based method was able to estimate FHR within 10% of the reference FHR values 96% of the time, with an accuracy of 97% for manually identified good quality segments in both of the independent test sets. Significance: This is the first work to publish open source code for FHR estimation from 1D-DUS data. The method was shown to satisfy estimations within 10% of the reference FHR values and it therefore defines a minimum accuracy for the field to match or surpass. Our work establishes a basis from which future methods can be developed to more accurately estimate FHR variability for assessing fetal wellbeing from 1D-DUS signals.