Miracle-dz/UniFAR-FTUs huggingface dataset:
Fiber Connectivity Density in Cerebral Small-Vessel Disease Patients With Mild Cognitive Impairment and Cerebral Small-Vessel Disease Patients With Normal Cognition

Abnormal structural connectivity of cerebral small-vessel disease (CSVD) is associated with cognitive impairment. But the different characteristics of structural connectivity have not been elucidated in early CSVD patients. The current study aimed to investigate the potential differences of structural connectivity in CSVD patients with mild cognitive impairment (MCI) and CSVD patients with normal cognition. Twenty-two CSVD patients with MCI, 34 CSVD patients with normal cognition, and 35 controls, who were age, sex, and education matched underwent diffusion tensor imaging and high resolution T1-weighted imaging. Clinical characteristics, lacunar infarct volume, white matter hyperintensity (WMH) volume, and global atrophy were quantitatively evaluated. Maps of fiber connectivity density (FiCD) were constructed and compared across groups in vertex levels. Pearson correlation was used to estimate the imaging–clinical relationships with control of general characteristics. CSVD patients with MCI had higher lesion load of WMH and lacunar infarcts, and correspondingly lower global FiCD value than CSVD patients with normal cognition (P < 0.01). Lacunar infarct (r = −0.318, P < 0.01) and WMH (r = −0.400, P < 0.01), but not global atrophy, age, or sex, were significantly correlated with the global FiCD value. CSVD patients with normal cognition showed decreased FiCD value mainly in the prefrontal areas (P < 0.01 with Monte Carlo correction). Compared with CSVD patients with normal cognition, CSVD patients with MCI showed significantly decreased FiCD value in enlarged frontal and parietal areas (P < 0.01 with Monte Carlo correction). Inter-group comparisons showed regional enhanced impairment of connectivity density in CSVD patients with MCI in the left superior frontal gyrus, the left precuneus, and the orbital part of the right inferior frontal gyrus (P < 0.01 with Monte Carlo correction). Regional FiCD value of frontal and parietal areas was associated with the cognitive function (P < 0.01). In conclusion, cognitively normal CSVD patients already have disruptions of structural connectivity. The extent and intensity of connectivity disruptions in frontal and parietal areas may underlie the mechanism of cognitive impairment in CSVD. Fiber connectivity density measurements may be helpful for quantitative description of structural cortical connectivity.
Interactive Effects of Rising Temperature and Nutrient Enrichment on Aquatic Plant Growth, Stoichiometry, and Palatability

The abundance and stoichiometry of aquatic plants are crucial for nutrient cycling and energy transfer in aquatic ecosystems. However, the interactive effects of multiple global environmental changes, including temperature rise and eutrophication, on aquatic plant stoichiometry and palatability remain largely unknown. Here, we hypothesized that (1) plant growth rates increase faster with rising temperature in nutrient-rich than nutrient-poor sediments; (2) plant carbon (C): nutrient ratios [nitrogen (N) and phosphorus (P)] respond differently to rising temperatures at contrasting nutrient conditions of the sediment; (3) external nutrient loading to the water column limits the growth of plants and decreases plant C:nutrient ratios; and that (4) changes in plant stoichiometry affect plant palatability. We used the common rooted submerged plant Vallisneria spiralis as a model species to test the effects of temperature and nutrient availability in both the sediment and the water column on plant growth and stoichiometry in a full-factorial experiment. The results confirmed that plants grew faster in nutrient-rich than nutrient-poor sediments with rising temperature, whereas external nutrient loading decreased the growth of plants due to competition by algae. The plant C: N and C: P ratios responded differently at different nutrient conditions to rising temperature. Rising temperature increased the metabolic rates of organisms, increased the nutrient availability in the sediment and enhanced plant growth. Plant growth was limited by a shortage of N in the nutrient-poor sediment and in the treatment with external nutrient loading to the water column, as a consequence, the limited plant growth caused an accumulation of P in the plants. Therefore, the effects of temperature on aquatic plant C:nutrient ratios did not only depend on the availability of the specific nutrients in the environment, but also on plant growth, which could result in either increased, unaltered or decreased plant C:nutrient ratios in response to temperature rise. Plant feeding trial assays with the generalist consumer Lymnaea stagnalis (Gastropoda) did not show effects of temperature or nutrient treatments on plant consumption rates. Overall, our results implicate that warming and eutrophication might interactively affect plant abundance and plant stoichiometry, and therefore influence nutrient cycling in aquatic ecosystems.
Step-by-Step, an E-Mental Health Intervention for Depression: A Mixed Methods Pilot Study From Lebanon

Background E-mental health is an established mode of delivering treatment for common mental disorders in many high income countries. However, evidence of its effectiveness in lower income countries is lacking. This mixed methods study presents lessons learned and preliminary data on the feasibility of a minimally guided e-mental health intervention in Lebanon. The aim was to pilot test Step-by-Step, a WHO guided e-mental health intervention, and research methods prior to future, controlled testing. Methods Participants were recruited using social media and advertisements in primary care clinics. Participants completed baseline and post-intervention questionnaires on depression symptoms (primary outcome, PHQ-8), anxiety symptoms, well-being, disability and self-perceived problem severity, and a client satisfaction questionnaire. In addition, seven completers, four drop-outs, 11 study staff, and four clinic managers were interviewed with responses thematically analyzed. Website analytics were used to understand participant behavior when using the website. Results A total of 129 participants signed up via the Step-by-Step website. Seventy-four participants started session 1 after completing pre-test questionnaires and 26 completed both baseline and post-intervention data. Among those who completed post-assessments, depression symptoms improved (PHQ-8 scores (t=5.62, p < 0.001 two-tailed, df = 25). Wilcoxon signed ranks tests showed a significant difference between baseline and post-Step-by-Step scores on all secondary outcome measures. Client satisfaction data was positive. Interview responses suggested that the intervention could be made more appropriate for younger, single people, more motivating, and easier to use. Those who utilized the support element of the intervention were happy with their relationship with the non-specialist support person (e-helper), though some participants would have preferred specialist support. E-helpers would have liked more training on complex cases. Website analytics showed that many users dropped out before intervention start, and that some re-entered screening data having been excluded from the study. Conclusion Step-by-Step skills and techniques, model of service integration, and its non-specialist support element are acceptable. Though the sample was small and non-controlled and drop-out was high, results suggest that it may be effective in reducing depression and anxiety symptoms and increasing well-being. Lessons learned will inform content revision, the development of an app version of Step-by-Step, and the research methodology of upcoming effectiveness studies.
Pregnancy Gestation Impacts on HIV-1-Specific Granzyme B Response and Central Memory CD4 T Cells

Pregnancy induces alterations in peripheral T-cell populations with both changes in subset frequencies and anti-viral responses found to alter with gestation. In HIV-1 positive women anti-HIV-1 responses are associated with transmission risk, however detailed investigation into both HIV-1-specific memory responses associated with HIV-1 control and T-cell subset changes during pregnancy have not been undertaken. In this study we aimed to define pregnancy and gestation related changes to HIV-1-specific responses and T-cell phenotype in ART treated HIV-1 positive pregnant women. Eleven non-pregnant and 24 pregnant HIV-1 positive women were recruited, peripheral blood samples taken, fresh cells isolated, and compared using ELISpot assays and flow cytometry analysis. Clinical data were collected as part of standard care, and non-parametric statistics used. Alterations in induced IFNγ, IL-2, IL-10, and granzyme B secretion by peripheral blood mononuclear cells in response to HIV-1 Gag and Nef peptide pools and changes in T-cell subsets between pregnant and non-pregnant women were assessed, with data correlated with participant clinical parameters and longitudinal analysis performed. Cross-sectional comparison identified decreased IL-10 Nef response in HIV-1 positive pregnant women compared to non-pregnant, while correlations exhibited reversed Gag and Nef cytokine and protease response associations between groups. Longitudinal analysis of pregnant participants demonstrated transient increases in Gag granzyme B response and in the central memory CD4 T-cell subset frequency during their second trimester, with a decrease in CD4 effector memory T cells from their second to third trimester. Gag and Nef HIV-1-specific responses diverge with pregnancy time-point, coinciding with relevant T-cell phenotype, and gestation associated immunological adaptations. Decreased IL-10 Nef and both increased granzyme B Gag response and central memory CD4 T cells implies that amplified antigen production is occurring, which suggests a period of compromised HIV-1 control in pregnancy.
Growing Up in a Changing Climate: How Temperature Affects the Development of Morphological, Behavioral and Physiological Traits of a Marsupial Mammal

Climate change is likely to affect many mammalian phenotypes, yet little is known whether and how phenotypic plasticity is involved in responding to thermal challenges during mammalian development. We investigated the effect of continuous cold or warm exposure during development on morphological, behavioral, and functional variables of yellow-footed antechinus (Antechinus flavipes), a semelparous Australian marsupial mammal. Captive-bred young were exposed to two ambient temperatures (Ta), cold (17°C) or warm (25°C), once weaned. Treatments were reversed and metabolic rate (MR) measurements repeated after 2 months. We measured body mass weekly, activity continuously, and MRs over a range of Ta once they were adults. Growth rate was similar in both groups, but was faster in males. Antechinus in the warm group were initially more active than the cold group and decreased activity when exposed to cold, whereas the cold group increased activity when exposed to warm. Interestingly, females changed their night-time activity when Ta was changed, whereas males changed their daytime activity. MRs were originally lower in the warm group in comparison to the cold group for both sexes and increased slightly for females, but not for males, after being exposed to cold. After exposure to warm Ta, the MRs of the cold group decreased significantly over the entire Ta-range for both sexes. Our results reveal that temperatures experienced during development can influence behavioral and physiological traits in antechinus. Such phenotypic plasticity is vital for a species that within 1 year is dependent on a single breeding event and experiences a complete population turnover.
Collagen Kinase Receptors as Potential Therapeutic Targets in Metastatic Colon Cancer

Colorectal cancer (CRC) is one of the leading causes of tumor-related death worldwide. While surgery can cure patients with early stage CRC, the 5-year survival rate is only 10% for patients with metastatic disease. Therefore, new anti-metastatic therapies are needed for this cancer. Metastatic spread defines the dissemination of cancer cells with tumor-initiating capacities from the primary tumor and their colonization of distinct organs, mainly the liver, for secondary tumor formation. Although the underlying mechanisms are not fully understood, components of the tumor microenvironment have gained strong interest. Among the known metastatic-promoting factors, collagens are extracellular matrix components that are deposited within the tumor, the tumor microenvironment, and at metastatic site(s), and are recognized to play essential roles during metastasis development. Here, we review recent findings on the metastatic role of the collagen receptors Discoidin Domain Receptors 1 and 2 (DDR1 and DDR2) in CRC and discuss the therapeutic value of targeting these receptor tyrosine kinases in this cancer.
Triple Network Model Dynamically Revisited: Lower Salience Network State Switching in Pre-psychosis

Emerging evidence has attributed altered network coordination between the default mode, central executive, and salience networks (DMN/CEN/SAL) to disturbances seen in schizophrenia, but little is known for at-risk psychosis stages. Moreover, pinpointing impairments in specific network-to-network interactions, although essential to resolve possibly distinct harbingers of conversion to clinically diagnosed schizophrenia, remains particularly challenging. We addressed this by a dynamic approach to functional connectivity, where right anterior insula brain interactions were examined through co-activation pattern (CAP) analysis. We utilized resting-state fMRI in 19 subjects suffering from subthreshold delusions and hallucinations (UHR), 28 at-risk for psychosis with basic symptoms describing only self-experienced subclinical disturbances (BS), and 29 healthy controls (CTR) matched for age, gender, handedness, and intelligence. We extracted the most recurring CAPs, compared their relative occurrence and average dwell time to probe their temporal expression, and quantified occurrence balance to assess the putative loss of competing relationships. Our findings substantiate the pivotal role of the right anterior insula in governing CEN-to-DMN transitions, which appear dysfunctional prior to the onset of psychosis, especially when first attenuated psychotic symptoms occur. In UHR subjects, it is longer active in concert with the DMN and there is a loss of competition between a SAL/DMN state, and a state with insula/CEN activation paralleled by DMN deactivation. These features suggest that abnormal network switching disrupts one's capacity to distinguish between the internal world and external environment, which is accompanied by inflexibility and an excessive awareness to internal processes reflected by prolonged expression of the right anterior insula-default mode co-activation pattern.
Metabolic Engineering a Model Oilseed Camelina sativa for the Sustainable Production of High-Value Designed Oils

Camelina sativa (L.) Crantz is an important Brassicaceae oil crop with a number of excellent agronomic traits including low water and fertilizer input, strong adaptation and resistance. Furthermore, its short life cycle and easy genetic transformation, combined with available data of genome and other “-omics” have enabled camelina as a model oil plant to study lipid metabolism regulation and genetic improvement. Particularly, camelina is capable of rapid metabolic engineering to synthesize and accumulate high levels of unusual fatty acids and modified oils in seeds, which are more stable and environmentally friendly. Such engineered camelina oils have been increasingly used as the super resource for edible oil, health-promoting food and medicine, biofuel oil and high-valued chemical production. In this review, we mainly highlight the latest advance in metabolic engineering towards the predictive manipulation of metabolism for commercial production of desirable bio-based products using camelina as an ideal platform. Moreover, we deeply analysis camelina seed metabolic engineering strategy and its promising achievements by describing the metabolic assembly of biosynthesis pathways for acetyl glycerides, hydroxylated fatty acids, medium-chain fatty acids, ω-3 long-chain polyunsaturated fatty acids, palmitoleic acid (ω-7) and other high-value oils. Future prospects are discussed, with a focus on the cutting-edge techniques in camelina such as genome editing application, fine directed manipulation of metabolism and future outlook for camelina industry development.
Stakeholder Assessment of Evidence-Based Guideline Dissemination and Implementation in a Dental Group Practice

Objective: This evaluation captures the perspectives of multiple stakeholders within a salaried dental care delivery organization (dentists, dental assistants, dental hygienists, and dental management) on the implementation of a pit-and-fissure sealant guideline in the Kaiser Permanente Dental Program. Also assessed is the role of formal processes and structures in providing a framework for guideline implementation. Methods: We collected qualitative data through field observations, stakeholder interviews (n = 6), and focus groups (30 participants in 5 focus groups). Field observation notes captured summaries of conversations and other activities. Interviews and focus groups were recorded and transcribed. We analyzed transcripts and field notes using a template analysis with NVivo 12 software to identify themes related to the existing implementation process of clinical guidelines and stakeholder perspectives on the strengths and weaknesses of this process. Results: Stakeholders perceived 2 main barriers for achieving implementation of the pit-and-fissure sealant guideline: 1) shortcomings in the implementation infrastructure resulting in lack of clarity about the roles and responsibilities in the guideline implementation process and lack of effective mechanisms to disseminate guideline content and 2) resource constraints, such as limited human, space, and material resources. Perceived opportunities for the dissemination and implementation of guidelines included recognition of the importance of guidelines in dental practice and well-functioning workflows within dental specialties. Conclusion: Our research points to the importance of developing and maintaining an infrastructure to ensure standardized, predictable mechanisms for implementation of guidelines and thereby promoting practice change. While addressing resource constraints may not be possible in all circumstances, an important step for improving guideline implementation—wherever feasible—would be the development of a robust implementation infrastructure that captures and delineates roles and responsibilities of different clinical actors in the guideline implementation process. Knowledge Transfer Statement: The results of this study can be used by health care leadership and administrators to understand possible reasons for a lack of guideline implementation and provide suggestions for establishing sustainable infrastructure to promote the adoption of clinical guidelines in salaried dental clinics.
Corticotropin-Releasing Factor Receptor-1 Neurons in the Lateral Amygdala Display Selective Sensitivity to Acute and Chronic Ethanol Exposure

Abstract The lateral amygdala (LA) serves as the point of entry for sensory information within the amygdala complex, a structure that plays a critical role in emotional processes and has been implicated in alcohol use disorders. Within the amygdala, the corticotropin-releasing factor (CRF) system has been shown to mediate some of the effects of both stress and ethanol, but the effects of ethanol on specific CRF1 receptor circuits in the amygdala have not been fully established. We used male CRF1:GFP reporter mice to characterize CRF1-expressing (CRF1+) and nonexpressing (CRF1−) LA neurons and investigate the effects of acute and chronic ethanol exposure on these populations. The CRF1+ population was found to be composed predominantly of glutamatergic projection neurons with a minority subpopulation of interneurons. CRF1+ neurons exhibited a tonic conductance that was insensitive to acute ethanol. CRF1− neurons did not display a basal tonic conductance, but the application of acute ethanol induced a δ GABAA receptor subunit-dependent tonic conductance and enhanced phasic GABA release onto these cells. Chronic ethanol increased CRF1+ neuronal excitability but did not significantly alter phasic or tonic GABA signaling in either CRF1+ or CRF1− cells. Chronic ethanol and withdrawal also did not alter basal extracellular GABA or glutamate transmitter levels in the LA/BLA and did not alter the sensitivity of GABA or glutamate to acute ethanol-induced increases in transmitter release. Together, these results provide the first characterization of the CRF1+ population of LA neurons and suggest mechanisms for differential acute ethanol sensitivity within this region.
The Utility of Diffusion Tensor Imaging in Neuromodulation: Moving Beyond Conventional Magnetic Resonance Imaging

Conventional targeting methods for neuromodulation therapies are insufficient for visualizing targets along white matter pathways and localizing targets in patient‐specific space. Diffusion tensor imaging (DTI) holds promise for enhancing neuromodulation targeting by allowing detailed visualization of white matter tracts and their connections on an individual level.
H+ Transport by K+ EXCHANGE ANTIPORTER3 Promotes Photosynthesis and Growth in Chloroplast ATP Synthase Mutants1[OPEN]

Proton antiport across the thylakoid membrane up-regulates photosynthesis and growth in an Arabidopsis mutant with low chloroplast ATP synthase levels and high proton motive force. The composition of the thylakoid proton motive force (pmf) is regulated by thylakoid ion transport. Passive ion channels in the thylakoid membrane dissipate the membrane potential (Δψ) component to allow for a higher fraction of pmf stored as a proton concentration gradient (ΔpH). K+/H+ antiport across the thylakoid membrane via K+ EXCHANGE ANTIPORTER3 (KEA3) instead reduces the ΔpH fraction of the pmf. Thereby, KEA3 decreases nonphotochemical quenching (NPQ), thus allowing for higher light use efficiency, which is particularly important during transitions from high to low light. Here, we show that in the background of the Arabidopsis (Arabidopsis thaliana) chloroplast (cp)ATP synthase assembly mutant cgl160, with decreased cpATP synthase activity and increased pmf amplitude, KEA3 plays an important role for photosynthesis and plant growth under steady-state conditions. By comparing cgl160 single with cgl160 kea3 double mutants, we demonstrate that in the cgl160 background loss of KEA3 causes a strong growth penalty. This is due to a reduced photosynthetic capacity of cgl160 kea3 mutants, as these plants have a lower lumenal pH than cgl160 mutants, and thus show substantially increased pH-dependent NPQ and decreased electron transport through the cytochrome b6f complex. Overexpression of KEA3 in the cgl160 background reduces pH-dependent NPQ and increases photosystem II efficiency. Taken together, our data provide evidence that under conditions where cpATP synthase activity is low, a KEA3-dependent reduction of ΔpH benefits photosynthesis and growth.