Miracle-dz/UniFAR-FTUs huggingface dataset:
Trading patterns within and between regions: an analysis of Gould-Fernandez brokerage roles

This study examines patterns of regionalisation in the International Trade Network (ITN). The study makes use of Gould – Fernandez brokerage to examine the roles countries play in the ITN linking different regional partitions. An examination of three ITNs is provided for three networks with varying levels of technological content, representing trade in high tech, medium tech, and low-tech goods. Simulated network data, based on multiple approaches including an advanced network model controlling for degree centralisation and clustering patterns, is compared to the observed data to examine whether the roles countries play within and between regions are a result of centralisation and clustering patterns. The findings indicate that the roles countries play between and within regions are indeed a result of centralisation patterns and chiefly clustering patterns; indicating a need to examine the presence of hubs when investigating regionalisation and globalisation patterns in the modern global economy.
Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines

Human cytomegalovirus (HCMV) is a common viral pathogen of solid organ transplant recipients, neonates, and HIV-infected individuals. HCMV encodes homologs of several host genes with the potential to influence viral persistence and/or pathogenesis. ABSTRACT Human cytomegalovirus (HCMV) is a beta-herpesvirus carried by ∼80% of the world’s population. Acute infections are asymptomatic in healthy individuals but generate diverse syndromes in neonates, solid organ transplant recipients, and HIV-infected individuals. The HCMV gene US28 encodes a homolog of a human chemokine receptor that is able to bind several chemokines and HIV gp120. Deep sequencing technologies were used to sequence US28 directly from 60 clinical samples from Indonesian HIV patients and Australian renal transplant recipients, healthy adults, and neonates. Molecular modeling approaches were used to predict whether nine nonsynonymous mutations in US28 may alter protein binding to a panel of six chemokines and two variants of HIV gp120. Ninety-two percent of samples contained more than one variant of HCMV, as defined by at least one nonsynonymous mutation. Carriage of these variants differed between neonates and adults, Australian and Indonesian samples, and saliva samples and blood leukocytes. Two nonsynonymous mutations (N170D and R267K) were associated with increased levels of immediate early protein 1 (IE-1) and glycoprotein B (gB) HCMV-reactive antibodies, suggesting a higher viral burden. Seven of the nine mutations were predicted to alter binding of at least one ligand. Overall, HCMV variants are common in all populations and have the potential to affect US28 interactions with human chemokines and/or gp120 and alter responses to the virus. The findings relied on deep sequencing technologies applied directly to clinical samples, so the variants exist in vivo. IMPORTANCE Human cytomegalovirus (HCMV) is a common viral pathogen of solid organ transplant recipients, neonates, and HIV-infected individuals. HCMV encodes homologs of several host genes with the potential to influence viral persistence and/or pathogenesis. Here, we present deep sequencing of an HCMV chemokine receptor homolog, US28, acquired directly from clinical specimens. Carriage of these variants differed between patient groups and was associated with different levels of circulating HCMV-reactive antibodies. These features are consistent with a role for US28 in HCMV persistence and pathogenesis. This was supported by in silico analyses of the variant sequences demonstrating altered ligand-binding profiles. The data delineate a novel approach to understanding the pathogenesis of HCMV and may impact the development of an effective vaccine.
Dynamics and origin of rebound viremia in SHIV-infected infant macaques following interruption of long-term ART

Understanding viral rebound in pediatric HIV-1 infection may inform the development of alternatives to lifelong antiretroviral therapy (ART) to achieve viral remission. We thus investigated viral rebound after analytical treatment interruption (ATI) in 10 infant macaques orally infected with SHIV.C. CH505 and treated with long-term ART. Rebound viremia was detected within 7 to 35 days of ATI in 9 of 10 animals, with posttreatment control of viremia seen in 5 of 5 Mamu-A*01+ macaques. Single-genome sequencing revealed that initial rebound virus was similar to viral DNA present in CD4+ T cells from blood, rectum, and lymph nodes before ATI. We assessed the earliest sites of viral reactivation immediately following ATI using ImmunoPET imaging. The largest increase in signal that preceded detectable viral RNA in plasma was found in the gastrointestinal (GI) tract, a site with relatively high SHIV RNA/DNA ratios in CD4+ T cells before ATI. Thus, the GI tract may be an initial source of rebound virus, but as ATI progresses, viral reactivation in other tissues likely contributes to the composition of plasma virus. Our study provides potentially novel insight into the features of viral rebound in pediatric infection and highlights the application of a noninvasive technique to monitor areas of HIV-1 expression in children.
Evidence for a deep, distributed and dynamic code for animacy in human ventral anterior temporal cortex

How does the human brain encode semantic information about objects? This paper reconciles two seemingly contradictory views. The first proposes that local neural populations independently encode semantic features; the second, that semantic representations arise as a dynamic distributed code that changes radically with stimulus processing. Combining simulations with a well-known neural network model of semantic memory, multivariate pattern classification, and human electrocorticography, we find that both views are partially correct: information about the animacy of a depicted stimulus is distributed across ventral temporal cortex in a dynamic code possessing feature-like elements posteriorly but with elements that change rapidly and nonlinearly in anterior regions. This pattern is consistent with the view that anterior temporal lobes serve as a deep cross-modal ‘hub’ in an interactive semantic network, and more generally suggests that tertiary association cortices may adopt dynamic distributed codes difficult to detect with common brain imaging methods.
Application of Environmental DNA for Monitoring Red Sea Bream Iridovirus at a Fish Farm

Environmental DNA (eDNA) could be applied in monitoring waterborne viruses of aquatic animals. However, there are few data for practical application of eDNA in fish farms for the control of disease outbreaks. ABSTRACT Red sea bream iridoviral disease (RSIVD) causes high economic damage in mariculture in Asian countries. However, there is little information on the source of infection and viral dynamics in fish farms. In the present study, the dynamics of RSIV in a fish farm that mainly reared juveniles and broodstocks of red sea bream (Pagrus major) were monitored over 3 years (2016 to 2018) by targeting environmental DNA (eDNA) of seawater. Our monitoring demonstrated that red sea bream iridovirus (RSIV) was detected from the eDNA at least 5 days before an RSIVD outbreak in the juveniles. The viral loads of eDNA during the outbreak were highly associated with the numbers for daily mortality, and they reached a peak of 106 copies/liter seawater in late July in 2017, when daily mortality exceeded 20,000 fish. In contrast, neither clinical signs nor mortality was observed in the broodstocks during the monitoring periods, whereas the broodstocks were confirmed to be virus carriers by an inspection in October 2017. Interestingly, the viral load of eDNA in the broodstock net pens (105 copies/liter seawater) was higher than that in the juvenile net pens (104 copies/liter seawater) just before the RSIVD outbreak in late June 2017. After elimination of all RSIV-infected surviving juveniles and 90% of broodstocks, few RSIV copies were detected in the eDNA in the fish farm from April 2018 onward (fewer than 102 copies/liter seawater). These results imply that the virus shed from the asymptomatically RSIV-infected broodstock was transmitted horizontally to the juveniles and caused further RSIVD outbreaks in the fish farm. IMPORTANCE Environmental DNA (eDNA) could be applied in monitoring waterborne viruses of aquatic animals. However, there are few data for practical application of eDNA in fish farms for the control of disease outbreaks. The results of our field research over 3 years targeting eDNA in a red sea bream (Pagrus major) fish farm implied that red sea bream iridoviral disease (RSIVD) outbreaks in juveniles originated from virus shedding from asymptomatically virus-infected broodstocks. Our work identifies an infection source of RSIVD in a fish farm via eDNA monitoring, and it could be applied as a tool for application in aquaculture to control fish diseases.
The Temporal Dynamics of Spontaneous Emotional Brain States and Their Implications for Mental Health

Abstract Temporal processes play an important role in elaborating and regulating emotional responding during routine mind wandering. However, it is unknown whether the human brain reliably transitions among multiple emotional states at rest and how psychopathology alters these affect dynamics. Here, we combined pattern classification and stochastic process modeling to investigate the chronometry of spontaneous brain activity indicative of six emotions (anger, contentment, fear, happiness, sadness, and surprise) and a neutral state. We modeled the dynamic emergence of these brain states during resting-state fMRI and validated the results across two population cohorts—the Duke Neurogenetics Study and the Nathan Kline Institute Rockland Sample. Our findings indicate that intrinsic emotional brain dynamics are effectively characterized as a discrete-time Markov process, with affective states organized around a neutral hub. The centrality of this network hub is disrupted in individuals with psychopathology, whose brain state transitions exhibit greater inertia and less frequent resetting from emotional to neutral states. These results yield novel insights into how the brain signals spontaneous emotions and how alterations in their temporal dynamics contribute to compromised mental health.
Adaptive replanning using cone beam CT for deformation of original CT simulation

During a course of radiation therapy, anatomical changes such as a decrease in tumour size or weight loss can trigger the need for repeating a computed tomography (CT) simulation scan in order to generate a new treatment plan. This adaptive approach requires a separate appointment for an additional CT scan which generates additional burden, cost, and radiation exposure for patients.
Medical Specialists' Perspectives on the Influence of Electronic Medical Record Use on the Quality of Hospital Care: Semistructured Interview Study

Background Numerous publications show that electronic medical records (EMRs) may make an important contribution to increasing the quality of care. There are indications that particularly the medical specialist plays an important role in the use of EMRs in hospitals. Objective The aim of this study was to examine how, and by which aspects, the relationship between EMR use and the quality of care in hospitals is influenced according to medical specialists. Methods To answer this question, a qualitative study was conducted in the period of August-October 2018. Semistructured interviews of around 90 min were conducted with 11 medical specialists from 11 different Dutch hospitals. For analysis of the answers, we used a previously published taxonomy of factors that can influence the use of EMRs. Results The professional experience of the participating medical specialists varied between 5 and 27 years. Using the previously published taxonomy, these medical specialists considered technical barriers the most significant for EMR use. The suboptimal change processes surrounding implementation were also perceived as a major barrier. A final major problem is related to the categories “social” (their relationships with the patients and fellow care providers), “psychological” (based on their personal issues, knowledge, and perceptions), and “time” (the time required to select, implement, and learn how to use EMR systems and subsequently enter data into the system). However, the medical specialists also identified potential technical facilitators, particularly in the assured availability of information to all health care professionals involved in the care of a patient. They see promise in using EMRs for medical decision support to improve the quality of care but consider these possibilities currently lacking. Conclusions The 11 medical specialists shared positive experiences with EMR use when comparing it to formerly used paper records. The fact that involved health care professionals can access patient data at any time they need is considered important. However, in practice, potential quality improvement lags as long as decision support cannot be applied because of the lack of a fully coded patient record.
Use of likelihood estimates for variances for the design and evaluation of multiregional clinical trials with heterogeneous variances

Globalized drug development studies, such as multiregional clinical trials (MRCTs), have attracted much attention due to their ability to expedite drug development and shorten the time lag of drug release. While observing the overall effect of a new drug, the region‐specific effects to support drug registration in constituent regions can also be evaluated. Several challenges arise in conducting MRCTs, such as the heterogeneity in the variability of the primary endpoint across regions. However, most of the existing statistical methods assume a common variability, which may not be valid in practice due to differences across regions (eg, diversities in ethnicity or disparities in medical culture/practice). We present a statistical method for the design and evaluation of MRCTs to consider the heterogeneous variability across regions. We assessed the overall sample size requirement and addressed the region‐specific sample size determination to establish the consistency of treatment effects between the specific region and the entire group. We demonstrate the proposed approach with numerical examples.
Superiority of Baseline Biomechanical Properties over Corneal Tomography in Predicting Keratoconus Progression

Objectives: To determine corneal biomechanical and tomographic factors associated with keratoconus (KC) progression. Materials and Methods: This study included 111 eyes of 111 KC patients who were followed-up for at least 1 year. Progression was defined as the presence of progressive change between the first two consecutive baseline visits in any single parameter (A, B, or C) ≥95% confidence interval or two parameters ≥80% confidence interval for the KC population evaluated by the Belin ABCD progression display. The eye with better initial tomographic findings was chosen as the study eye. Analyzed Pentacam parameters were maximum keratometry (Kmax), minimum pachymetry (Kmin), central corneal thickness, thinnest corneal thickness, 90° vertical anterior and posterior coma data in Zernike analysis, and Belin Ambrosio Enhanced Ectasia Display Final D value. Corneal hysteresis (CH) and corneal resistance factor (CRF) were analyzed together with the waveform parameters obtained with Ocular Response Analyzer (ORA). Factors related to KC progression were evaluated using t-tests and logistic regression tests. Statistical significance was accepted as p<0.05. Results: There were 44 (mean age: 27.1±8.5 years, female: 25) and 67 (mean age: 31.1±9.1 years, female: 36) patients in the progressive and non-progressive groups, respectively. Although Pentacam parameters along with CH and CRF were similar between the two groups, ORA waveform parameter derived from the second applanation signal p2area was statistically significantly lower in the progressive group (p=0.02). Each 100-unit decrease in p2area increased the likelihood of keratoconus progression by approximately 30% in the logistic regression analysis (β=0.707, p=0.001, model r2=0.27). Conclusion: Parameters derived from the second applanation signal of ORA may be superior to conventional ORA parameters and corneal tomography in predicting KC progression.
iASPP contributes to cell cortex rigidity, mitotic cell rounding, and spindle positioning

Mangon et al. show that the protein iASPP, known as an inhibitor of p53, also interacts with the microtubule plus-end protein EB1 and the plasma membrane-to-actin cross-linker Myo1c to regulate mitotic cell cortical stiffness, mitotic rounding, and mitotic spindle positioning.
Increased FUN14 domain containing 1 (FUNDC1) ubiquitination level inhibits mitophagy and alleviates the injury in hypoxia-induced trophoblast cells

ABSTRACT Preeclampsia (PE) is a pregnancy disorder characterized by excessive trophoblast cell death. This study aims to explore the exact mechanism of the ubiquitination level of FUN14 domain containing 1 (FUNDC1) in mitophagy and injury in hypoxic trophoblast cells. In this study, HTR-8/SVneo trophoblast cells were cultured under normoxic and hypoxic conditions and PE mouse model was established. We found low ubiquitination level of FUNDC1 in hypoxic trophoblast cells and placenta of pregnant women with PE. Proteasome inhibitor MG-132 and protease activator MF-094 were added into HTR-8/SVneo trophoblast cells. Proteasome inhibitor MG-132 decreased FUNDC1 ubiquitination level while protease activator MF-094 increased FUNDC1 ubiquitination level. Inhibition of FUNDC1 ubiquitination promoted mitophagy and mitochondrial membrane potential (Δψm) in normoxic trophoblast cells, increased levels of reactive oxygen species (ROS) and malondialdehyde (MDA) and decreased levels of glutathione (GSH) and superoxide dismutase (SOD). In addition, FUNDC1 ubiquitination alleviated cell injury in PE mice in vivo. In conclusion, increased FUNDC1 ubiquitination level inhibited mitophagy and Δψm changes in hypoxic trophoblast cells, and thus alleviated oxidative injury.
Autism-Like Behavioral Phenotypes in Mice Treated with Systemic N-Methyl-D-Aspartate

Autism spectrum disorder (ASD) having core characteristics of social interaction problems and repetitive behaviors and interests affects individuals at varying degrees and comorbidities, making it difficult to determine the precise etiology underlying the symptoms. Given its heterogeneity, ASD is difficult to treat and the development of therapeutics is slow due to the scarcity of animal models that are easy to produce and screen with. Based on the theory of excitation/inhibition imbalance in the brain with ASD which involves glutamatergic and/or GABAergic neurotransmission, a pharmacologic agent to modulate these receptors might be a good starting point for modeling. N-methyl-D-aspartic acid (NMDA) is an amino acid derivative acting as a specific agonist at the NMDA receptor and therefore imitates the action of the neurotransmitter glutamate on that receptor. In contrast to glutamate, NMDA selectively binds to and regulates the NMDA receptor, but not other glutamate receptors such as AMPA and kainite receptors. Given this role, we aimed to determine whether NMDA administration could result in autistic-like behavior in adolescent mice. Both male and female mice were treated with saline or NMDA (50 and 75 mg/kg) and were tested on various behavior experiments. Interestingly, acute NMDA-treated mice showed social deficits and repetitive behavior similar to ASD phenotypes. These results support the excitation/inhibition imbalance theory of ASD and that NMDA injection can be used as a pharmacologic model of ASD-like behaviors.
18 F-Fludeoxyglucose-Positron Emission Tomography/Computed Tomography and Laparoscopy for Staging of Locally Advanced Gastric Cancer

IMPORTANCE The optimal staging for gastric cancer remains a matter of debate. OBJECTIVE To evaluate the value of 18 F-fludeoxyglucose–positron emission tomography with computed tomography (FDG-PET/CT) and staging laparoscopy (SL) in addition to initial staging by means of gastroscopy and CT in patients with locally advanced gastric cancer. DESIGN,SETTING,ANDPARTICIPANTS Thismulticenterprospective,observationalcohort study included
NONPIGMENTED VERSUS PIGMENTED: HEALTH VARIABLES AND GENETICS OF ALBINO FLORIDA GREEN TURTLE (CHELONIA MYDAS) HATCHLINGS COMPARED WITH NORMALLY PIGMENTED HATCHLINGS FROM THE SAME CLUTCH

Abstract: At the time of hatchling emergence from a nest laid on Juno Beach, Florida, US, by a normally pigmented green turtle (Chelonia mydas), 23 albino hatchlings and 75 normally pigmented hatchlings were observed. This condition is rarely seen in sea turtles, and little is known about blood analytes and genetics of albino wildlife to date. Therefore, the objective of our study was to assess and compare morphometric measurements (mass, minimum straight carapace length, body condition index), carapacial scute anomalies, a suite of hematologic and plasma biochemical analytes, and two glucose analysis methodologies (glucometer and dry chemistry analysis) in albino (n=20) versus normally pigmented (n=24) hatchlings from this nest. Genetic analyses were completed to identify paternal contributions of hatchlings and to test Mendelian inheritance assumptions. Although morphometric measurements, scute anomalies, and leukocyte morphology were similar between albino and normally pigmented hatchlings, several differences were observed in blood analyte data: immature erythrocytes, packed cell volume, heterophil:lymphocyte ratio, and glucose concentrations (by both methodologies) were significantly higher, whereas absolute immature heterophils, absolute lymphocytes, number of erythrocyte micronuclei, sodium, and chloride were significantly lower in albino hatchlings compared with normally pigmented hatchlings. Considerations for these differences include a stress response from sampling (e.g., timing of procedures or possibly from photosensitivity or reduced visual acuity in albinos) and different osmoregulation, which may reflect physiologic variations or stress. There was a small positive bias (0.10 mmol/L) with glucose by glucometer, similar to reports in other sea turtle species and confirming its suitability for use in hatchlings. All albino hatchlings analyzed (n=10) were from the same father, but the normally pigmented hatchlings (n=24) were from two other fathers. These findings provide insight into the physiology and genetics of albinism in sea turtles.