Miracle-dz/UniFAR-FTUs huggingface dataset:
Intrinsic Functional Boundaries of Lateral Frontal Cortex in the Common Marmoset Monkey

The common marmoset (Callithrix jacchus) is a small New World primate species that has been recently targeted as a potentially powerful preclinical model of human prefrontal cortex dysfunction. Although the structural boundaries of frontal cortex were described in marmosets at the start of the 20th century (Brodmann, 1909) and refined more recently (Paxinos et al., 2012), the broad functional boundaries of marmoset frontal cortex have yet to be established. In this study, we sought to functionally derive boundaries of the marmoset lateral frontal cortex (LFC) using ultra-high field (9.4 T) resting-state functional magnetic resonance imaging (RS-fMRI). We collected RS-fMRI data in seven (four females, three males) lightly anesthetized marmosets and used a data-driven hierarchical clustering approach to derive subdivisions of the LFC based on intrinsic functional connectivity. We then conducted seed-based analyses to assess the functional connectivity between these clusters and the rest of the brain. The results demonstrated seven distinct functional clusters within the LFC. The functional connectivity patterns of these clusters with the rest of the brain were also found to be distinct and organized along a rostrocaudal gradient, consonant with those found in humans and macaques. Overall, these results support the view that marmosets are a promising preclinical modeling species for studying LFC dysfunction related to neuropsychiatric or neurodegenerative human brain diseases. SIGNIFICANCE STATEMENT The common marmoset is a New World primate that has garnered recent attention as a powerful complement to canonical Old World primate (e.g., macaques) and rodent models (e.g., rats, mice) for preclinical modeling of the human brain in healthy and diseased states. A critical step in the development of marmosets for such models is to characterize functional network topologies of frontal cortex in healthy, normally functioning marmosets, that is, how these circuitries are functionally divided and how those topologies compare to human circuitry. To our knowledge, this is the first study to demonstrate functional boundaries of the lateral frontal cortex and the corresponding network topologies in marmoset monkeys.
The Utility of Preoperative Arteriography for Free Flap Planning in Patients with Chronic Lower Extremity Wounds

Background: In patients with lower extremity wounds, free tissue transfer is often the last option before amputation, making it crucial to optimize preoperative planning to prevent flap breakdown. No consensus exists regarding preoperative vascular workup before lower extremity free tissue transfer. In this study, the authors analyzed the utility of using arteriography for lower extremity free flap planning. Methods: A retrospective review was performed of 57 patients who underwent lower extremity arteriography and 59 free flap operations for lower extremity wounds between November of 2014 and August of 2017. Findings were used to guide flap recipient vessel selection. Arterial abnormality was addressed by means of endovascular intervention, where appropriate. Encountered abnormality was described and patient demographics, comorbidities, and outcomes were analyzed for correlation with abnormal angiographic studies. Results: Angiographic abnormalities were observed in 40 patients (67.8 percent), including 23 (57.5 percent) with stenosis/occlusion, 20 (50.0 percent) with atretic/nonvisualized vessels, and 11 (27.5 percent) requiring endovascular intervention. Stenosis/occlusion was detected in nine patients (15.3 percent) with no previously known arterial disease, leading to a new diagnosis of peripheral vascular disease. The flap survival rate was 98.3 percent, six patients (10.2 percent) ultimately progressed to amputation, and 53 patients (89.8 percent) were able to continue community ambulation at a mean follow-up time of 15.1 ± 9.51 months (range, 1.67 to 35.2 months). After arteriography, two patients (3.39 percent) suffered contrast-induced acute kidney injury. No other complications were noted. Conclusion: Preoperative lower extremity arteriography aids in the diagnosis of peripheral vascular disease, allows for timely endovascular intervention, and allows for optimal flap recipient vessel selection with a low complication rate. CLINICAL QUESTION/LEVEL OF EVIDENC: Diagnostic, IV.
Using deep neural networks along with dimensionality reduction techniques to assist the diagnosis of neurodegenerative disorders

The analysis of neuroimaging data is frequently used to assist the diagnosis of neurodegenerative disorders such as Alzheimer's disease (AD) or Parkinson's disease (PD) and has become a routine procedure in the clinical practice. During the past decade, the pattern recognition community has proposed a number of machine learning-based systems that automatically analyse neuroimaging data in order to improve the diagnosis. However, the high dimensionality of the data is still a challenge and there is room for improvement. The development of novel classification frameworks as TensorFlow, recently released as open source by Google Inc., represents an opportunity to continue evolving these systems. In this work, we demonstrate several computer-aided diagnosis (CAD) systems based on Deep Neural Networks that improve the diagnosis for AD and PD and outperform those based on classical classifiers. In order to address the small sample size problem we evaluate two dimensionality reduction algorithms based on Principal Component Analysis and Non-Negative Matrix Factorization (NNMF), respectively. The performance of developed CAD systems is assessed using 4 datasets with neuroimaging data of different modalities.
Crime, criminal networks and the survival strategies of the poor in early eighteenth-century London

This morning one Rebecca Hart, a poor Woman belonging to the Parish of St. James’s, was committed to Prison for stealing several Quantities of Coals, the Property of Mr. Nathan Robley. It was sworn against her that she had declared, ‘It was no Sin in the Poor to rob the Rich; and that if it was, J— C— had died to procure the Pardon of all such Sinners. ’ The Prisoner all the Time she was before the Justice, appeared with uplifted Eyes, and behaved herself as if she had been engaged in her Devotions, appealing to Heaven for her Innocence, and invoking the most sacred Names as Witnesses of her not having committed a Fact, for which there appeared unquestionable Evidence.1
Virus-inclusive single-cell RNA sequencing reveals the molecular signature of progression to severe dengue

Significance A fraction of the 400 million people infected with dengue annually progresses to severe dengue (SD). Yet, there are currently no biomarkers to predict disease progression. We profiled the landscape of host transcripts and viral RNA in thousands of single blood cells from dengue patients prior to progressing to SD. We discovered cell type-specific immune activation and candidate predictive biomarkers. We also determined preferential virus association with specific cell populations, particularly naive B cells and monocytes. We explored immune activation of bystander cells, clonality and somatic evolution of adaptive immune repertoires, as well as viral genomics. This multifaceted approach could advance understanding of pathogenesis of any viral infection, map an atlas of infected cells, and promote the development of prognostics. Dengue virus (DENV) infection can result in severe complications. However, the understanding of the molecular correlates of severity is limited, partly due to difficulties in defining the peripheral blood mononuclear cells (PBMCs) that contain DENV RNA in vivo. Accordingly, there are currently no biomarkers predictive of progression to severe dengue (SD). Bulk transcriptomics data are difficult to interpret because blood consists of multiple cell types that may react differently to infection. Here, we applied virus-inclusive single-cell RNA-seq approach (viscRNA-Seq) to profile transcriptomes of thousands of single PBMCs derived early in the course of disease from six dengue patients and four healthy controls and to characterize distinct leukocyte subtypes that harbor viral RNA (vRNA). Multiple IFN response genes, particularly MX2 in naive B cells and CD163 in CD14+ CD16+ monocytes, were up-regulated in a cell-specific manner before progression to SD. The majority of vRNA-containing cells in the blood of two patients who progressed to SD were naive IgM B cells expressing the CD69 and CXCR4 receptors and various antiviral genes, followed by monocytes. Bystander, non-vRNA–containing B cells also demonstrated immune activation, and IgG1 plasmablasts from two patients exhibited clonal expansions. Lastly, assembly of the DENV genome sequence revealed diversity at unexpected sites. This study presents a multifaceted molecular elucidation of natural dengue infection in humans with implications for any tissue and viral infection and proposes candidate biomarkers for prediction of SD.
Towards Personalized, Brain-Based Behavioral Intervention for Transdiagnostic Anxiety: Transient Neural Responses to Negative Images Predict Outcomes Following a Targeted Computer-Based Intervention

Objective: Clinical anxiety is prevalent, highly comorbid with other conditions, and associated with significant medical morbidity, disability, and public health burden. Excessive attentional deployment toward threat is a transdiagnostic dimension of anxiety seen at both initial and sustained stages of threat processing. However, group-level observations of these phenomena mask considerable within-group heterogeneity that has been linked to treatment outcomes, suggesting that a transdiagnostic, individual differences approach may capture critical, clinically relevant information. Method: Seventy clinically anxious individuals were randomized to receive 8 sessions of attention bias modification (ABM; n = 41 included in analysis), a computer-based mechanistic intervention that specifically targets initial stages of threat processing, or a sham control (n = 21). Participants completed a mixed block/event-related functional MRI task optimized to discriminate transient from sustained neural responses to threat. Results: Larger transient responses across a wide range of cognitive-affective regions (e.g., ventrolateral prefrontal cortex, anterior cingulate cortex, amygdala) predicted better clinical outcomes following ABM, in both a priori anatomical regions and whole-brain analyses; sustained responses did not. A spatial pattern recognition algorithm using transient threat responses successfully discriminated the top quartile of ABM responders with 68% accuracy. Conclusions: Neural alterations occurring on the relatively transient timescale that is specifically targeted by ABM predict favorable clinical outcomes. Results inform how to expand on the initial promise of neurocognitive treatments like ABM by fine-tuning their clinical indications (e.g., through personalized mechanistic intervention relevant across diagnoses) and by increasing the range of mechanisms that can be targeted (e.g., through synergistic treatment combinations and/or novel neurocognitive training protocols designed to tackle identified predictors of nonresponse).
Perceptions of asymptomatic malaria infection and their implications for malaria control and elimination in Laos

Background In the Greater Mekong Sub-region (GMS), malaria elimination efforts are targeting the asymptomatic parasite reservoirs. Understanding community perceptions about asymptomatic malaria infections and interventions that target this reservoir is critical to the design of community engagement. This article examines knowledge, attitudes, perceptions and practices related to asymptomatic malaria infections and mass drug administration (MDA) in malaria-endemic villages in southern Savannakhet Province, Laos. Methods A questionnaire consisting of questions on socio-demographic characteristics, knowledge, attitudes, perceptions and practices on malaria and MDA was administered to each household head or representative (n = 281) in four villages. These topics were also further discussed in 12 single-gender focus group discussions (FGDs). The FGDs were conducted in all four villages and consisted of eight to 10 participants. Results A minority (14.2%; 40/281) of respondents agreed that a seemingly healthy person could have malaria parasite in his or her blood. Half (52%; 146/281) disagreed and one third (33.8%, 95/281) were unsure. Respondents who responded that “MDA aims to cure everyone” [AOR = 4.6; CI: 1.6–13.1], “MDA is to make our community malaria free” [AOR = 3.3; CI: 1.3–8.1] and “I will take part in future MDA” [AOR = 9.9; CI: 1.2–78.8] were more likely to accept the idea of asymptomatic malaria. During FGDs, respondents recalled signs and symptoms of malaria (fever, chills and headache), and described malaria as a major health problem. Symptomatic and asymptomatic malaria infections were associated with their work in the forest and living conditions. Measures described to eliminate malaria included using mosquito nets, wearing long-sleeved clothes and taking medicine when symptomatic. Most respondents were unaware of MDA as a tool to eliminate malaria. Conclusions Awareness of asymptomatic malaria infections, and MDA as a tool to eliminate malaria, was low. With the need to target asymptomatic malaria carriers for elimination efforts in the GMS, as well as informing target groups about asymptomatic infection, accompanying community engagement must build trust in interventions through the active collaboration of government stakeholders, key local persons and community members. This entails training and devolving responsibilities to the community members to implement and sustain the control and elimination efforts.
Cooperative hunting in a discrete predator–prey system

We propose and investigate a discrete-time predator–prey system with cooperative hunting in the predator population. The model is constructed from the classical Nicholson–Bailey host-parasitoid system with density dependent growth rate. A sufficient condition based on the model parameters for which both populations can coexist is derived, namely that the predator’s maximal reproductive number exceeds one. We study existence of interior steady states and their stability in certain parameter regimes. It is shown that the system behaves asymptotically similar to the model with no cooperative hunting if the degree of cooperation is small. Large cooperative hunting, however, may promote persistence of the predator for which the predator would otherwise go extinct if there were no cooperation.
Identifying Preanalytic and Postanalytic Laboratory Quality Gaps Using a Data Warehouse and Structured Multidisciplinary Process.

CONTEXT. — The laboratory total testing process includes preanalytic, analytic, and postanalytic phases, but most laboratory quality improvement efforts address the analytic phase. Expanding quality improvement to preanalytic and postanalytic phases via use of medical data warehouses, repositories that include clinical, utilization, and administrative data, can improve patient care by ensuring appropriate test utilization. Cross-department, multidisciplinary collaboration to address gaps and improve patient and system outcomes is beneficial. OBJECTIVE. — To demonstrate medical data warehouse utility for characterizing laboratory-associated quality gaps amenable to preanalytic or postanalytic interventions. DESIGN. — A multidisciplinary team identified quality gaps. Medical data warehouse data were queried to characterize gaps. Organizational leaders were interviewed about quality improvement priorities. A decision aid with elements including national guidelines, local and national importance, and measurable outcomes was completed for each gap. RESULTS. — Gaps identified included (1) test ordering; (2) diagnosis, detection, and documentation, and (3) high-risk medication monitoring. After examination of medical data warehouse data including enrollment, diagnoses, laboratory, pharmacy, and procedures for baseline performance, high-risk medication monitoring was selected, specifically alanine aminotransferase, aspartate aminotransferase, complete blood count, and creatinine testing among patients receiving disease-modifying antirheumatic drugs. The test utilization gap was in monitoring timeliness (eg, >60% of patients had a monitoring gap exceeding the guideline recommended frequency). Other contributors to selecting this gap were organizational enthusiasm, regulatory labeling, and feasibility of a significant laboratory role in addressing the gap. CONCLUSIONS. — A multidisciplinary process facilitated identification and selection of a laboratory medicine quality gap. Medical data warehouse data were instrumental in characterizing gaps.
Beyond confidence: Development of a measure assessing the 5C psychological antecedents of vaccination

Background Monitoring the reasons why a considerable number of people do not receive recommended vaccinations allows identification of important trends over time, and designing and evaluating strategies to address vaccine hesitancy and increase vaccine uptake. Existing validated measures assessing vaccine hesitancy focus primarily on confidence in vaccines and the system that delivers them. However, empirical and theoretical work has stated that complacency (not perceiving diseases as high risk), constraints (structural and psychological barriers), calculation (engagement in extensive information searching), and aspects pertaining to collective responsibility (willingness to protect others) also play a role in explaining vaccination behavior. The objective was therefore to develop a validated measure of these 5C psychological antecedents of vaccination. Methods and findings Three cross-sectional studies were conducted. Study 1 uses factor analysis to develop an initial scale and assesses the sub-scales’ convergent, discriminant, and concurrent validity (N = 1,445, two German convenience-samples). In Study 2, a sample representative regarding age and gender for the German population (N = 1,003) completed the measure for vaccination in general and for specific vaccinations to assess the potential need for a vaccine-specific wording of items. Study 3 compared the novel scale’s performance with six existing measures of vaccine hesitancy (N = 350, US convenience-sample). As an outcome, a long (15-item) and short (5-item) 5C scale were developed as reliable and valid indicators of confidence, complacency, constraints, calculation, and collective responsibility. The 5C sub-scales correlated with relevant psychological concepts, such as attitude (confidence), perceived personal health status and invulnerability (complacency), self-control (constraints), preference for deliberation (calculation), and communal orientation (collective responsibility), among others. The new scale provided similar results when formulated in a general vs. vaccine-specific way (Study 2). In a comparison of seven measures the 5C scale was constantly among the scales that explained the highest amounts of variance in analyses predicting single vaccinations (between 20% and 40%; Study 3). The present studies are limited to the concurrent validity of the scales. Conclusions The 5C scale provides a novel tool to monitor psychological antecedents of vaccination and facilitates diagnosis, intervention design and evaluation. Its short version is suitable for field settings and regular global monitoring of relevant antecedents of vaccination.
Cross-Species Immune Recognition Between Plasmodium vivax Duffy Binding Protein Antibodies and the Plasmodium falciparum Surface Antigen VAR2CSA

Background In pregnancy, Plasmodium falciparum parasites express the surface antigen VAR2CSA, which mediates adherence of red blood cells to chondroitin sulfate A (CSA) in the placenta. VAR2CSA antibodies are generally acquired during infection in pregnancy and are associated with protection from placental malaria. We observed previously that men and children in Colombia also had antibodies to VAR2CSA, but the origin of these antibodies was unknown. Here, we tested whether infection with Plasmodium vivax is an alternative mechanism of acquisition of VAR2CSA antibodies. Methods We analyzed sera from nonpregnant Colombians and Brazilians exposed to P. vivax and monoclonal antibodies raised against P. vivax Duffy binding protein (PvDBP). Cross-reactivity to VAR2CSA was characterized by enzyme-linked immunosorbent assay, immunofluorescence assay, and flow cytometry, and antibodies were tested for inhibition of parasite binding to CSA. Results Over 50% of individuals had antibodies that recognized VAR2CSA. Affinity-purified PvDBP human antibodies and a PvDBP monoclonal antibody recognized VAR2CSA, showing that PvDBP can give rise to cross-reactive antibodies. Importantly, the monoclonal antibody inhibited parasite binding to CSA, which is the primary in vitro correlate of protection from placental malaria. Conclusions These data suggest that PvDBP induces antibodies that functionally recognize VAR2CSA, revealing a novel mechanism of cross-species immune recognition to falciparum malaria.
WRF-Chem modeling of particulate matter in the Yangtze River Delta region: Source apportionment and its sensitivity to emission changes

China has been troubled by high concentrations of fine particulate matter (PM2.5) for many years. Up to now, the pollutant sources are not yet fully understood and the control approach still remains highly uncertain. In this study, four month-long (January, April, July and October in 2015) WRF-Chem simulations with different sensitivity experiments were conducted in the Yangtze River Delta (YRD) region of eastern China. The simulated results were compared with abundant meteorological and air quality observations at 138 stations in 26 YRD cities. Our model well captured magnitudes and variations of the observed PM2.5, with the normal mean biases (NMB) less than ±20% for 19 out of the 26 YRD cities. A series of sensitivity simulations were conducted to quantify the contributions from individual source sectors and from different regions to the PM2.5 in the YRD region. The calculated results show that YRD local source contributed 64% of the regional PM2.5 concentration, while outside transport contributed the rest 36%. Among the local sources, industry activity was the most significant sector in spring (25%), summer (36%) and fall (33%), while residential source was more important in winter (38%). We further conducted scenario simulations to explore the potential impacts of varying degrees of emission controls on PM2.5 reduction. The result demonstrated that regional cooperative control could effectively reduce the PM2.5 level. The proportionate emission controls of 10%, 20%, 30%, 40% and 50% could reduce the regional mean PM2.5 concentrations by 10%, 19%, 28%, 37% and 46%, respectively, and for places with higher ambient concentrations, the mitigation efficiency was more significant. Our study on source apportionment and emission controls can provide useful information on further mitigation actions.
Neutropenia in the age of genetic testing: Advances and challenges

Identification of genetic causes of neutropenia informs precision medicine approaches to medical management and treatment. Accurate diagnosis of genetic neutropenia disorders informs treatment options, enables risk stratification, cancer surveillance, and attention to associated medical complications. The rapidly expanding genetic testing options for the evaluation of neutropenia have led to exciting advances but also new challenges. This review provides a practical guide to germline genetic testing for neutropenia.