Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of Insulin Glargine and Liraglutide Therapy on Liver Fat as Measured by Magnetic Resonance in Patients With Type 2 Diabetes: A Randomized Trial

OBJECTIVE This study determined the effects of insulin versus liraglutide therapy on liver fat in patients with type 2 diabetes inadequately controlled with oral agents therapy, including metformin. RESEARCH DESIGN AND METHODS Thirty-five patients with type 2 diabetes inadequately controlled on metformin monotherapy or in combination with other oral antidiabetic medications were randomized to receive insulin glargine or liraglutide therapy for 12 weeks. The liver proton density fat fraction (PDFF) was measured by MRS. The mean liver PDFF, the total liver volume, and the total liver fat index were measured by MRI. The Student t test, the Fisher exact test, and repeated-measures ANOVA were used for statistical analysis. RESULTS Insulin treatment was associated with a significant improvement in glycated hemoglobin (7.9% to 7.2% [62.5 to 55.2 mmol/mol], P = 0.005), a trend toward a decrease in MRS-PDFF (12.6% to 9.9%, P = 0.06), and a significant decrease in liver mean MRI-PDFF (13.8% to 10.6%, P = 0.005), liver volume (2,010.6 to 1,858.7 mL, P = 0.01), and the total liver fat index (304.4 vs. 209.3 % ⋅ mL, P = 0.01). Liraglutide treatment was also associated with a significant improvement in glycated hemoglobin (7.6% to 6.7% [59.8 to 50.2 mmol/mol], P < 0.001) but did not change MRS-PDFF (P = 0.80), liver mean MRI-PDFF (P = 0.15), liver volume (P = 0.30), or the total liver fat index (P = 0.39). CONCLUSIONS The administration of insulin glargine therapy reduced the liver fat burden in patients with type 2 diabetes. However, the improvements in the liver fat fraction and glycemia control were not significantly different from those in the liraglutide group.
The Use of Ground-Based GPS Precipitable Water Measurements over China to Assess Radiosonde and ERA-Interim Moisture Trends and Errors from 1999 to 2015

AbstractGlobal positioning system (GPS) data from over 260 ground-based permanent stations in China covering the period from 1 March 1999 to 30 April 2015 were used to estimate precipitable water (PW) above each site with an accuracy of about 0.75 mm. Four types of radiosondes (referred to as GZZ2, GTS1, GTS1-1, and GTS1-2) were used in China during this period. Instrumentation type changes in radiosonde records were identified by comparing PW calculated from GPS and radiosonde data. Systematic errors in different radiosonde types introduced significant biases to the estimated PW trends at stations where more than one radiosonde type was used. Estimating PW trends from reanalysis products (ERA-Interim), which assimilate the unadjusted radiosonde humidity data, resulted in an artificial downward PW trend at almost all stations in China. The statistically significant GPS PW trends are predominantly positive, consistent in sign with the increase in moisture expected from the Clausius–Clapeyron relation due t.
Resting Memory CD8+ T Cells are Hyperreactive to Antigenic Challenge In Vitro

The characteristics of CD8+ T cells responsible for memory responses are still largely unknown. Particularly, it has not been determined whether different activation thresholds distinguish naive from memory CD8+ T cell populations. In most experimental systems, heterogeneous populations of primed CD8+ T cells can be identified in vivo after immunization. These cells differ in terms of cell cycle status, surface phenotype, and/or effector function. This heterogeneity has made it difficult to assess the activation threshold and the relative role of these subpopulations in memory responses. In this study we have used F5 T cell receptor transgenic mice to generate a homogeneous population of primed CD8+ T cells. In the F5 transgenic mice, peptide injection in vivo leads to activation of most peripheral CD8+ T cells. In vivo BrdU labeling has been used to follow primed T cells over time periods spanning several weeks after peptide immunization. Our results show that the majority of primed CD8+ T cells generated in this system are not cycling and express increased levels of CD44 and Ly6C. These cells remain responsive to secondary peptide challenge in vivo as evidenced by short term upregulation of activation markers such as CD69 and CD44. The activation thresholds of naive and primed CD8+ T cells were compared in vitro. We found that CD8+ T cells from primed mice are activated by peptide concentrations 10–50-fold lower than naive mice. In addition, the kinetics of interleukin 2Rα chain upregulation by primed CD8+ T cells differ from naive CD8+ T cells. These primed hyperresponsive CD8+ T cells might play an important role in the memory response.
Statistical group sparse beamforming for green Cloud-RAN via large system analysis

In this paper, we develop a statistical group sparse beamforming framework to minimize the network power consumption for green cloud radio access networks (Cloud-RANs). It will promote group sparsity structures in the beamforming vectors, which will provide a good indicator for remote radio head (RRH) ordering to enable adaptive RRH selection for power saving. In contrast to the previous works that depend heavily on instantaneous channel state information (CSI), the proposed algorithm only depends on the long-term channel state attenuation for RRH ordering, which does not require frequent update, thereby significantly reducing the computation overhead. This is achieved by developing a smoothed ℓp-minimization approach to induce group sparsity in beamforming vectors, followed by an iterative reweighted-ℓ2 algorithm via the principles of the majorization-minimization (MM) algorithm and the Lagrangian duality theory. With the well-structured closed-form solutions at each iteration, we further leverage the large-dimensional random matrix theory to derive deterministic approximations for the squared ℓ2-norm of the induced group sparse beamforming vectors in the large system regimes. The deterministic approximation results only depend on statistical CSI and will guide the RRH ordering. Simulation results demonstrate the near-optimal performance of the proposed algorithm, even in finite systems.
Do Childhood Adversities Predict Suicidality? Findings from the General Population of the Metropolitan Area of São Paulo, Brazil

Background Childhood adversities have been associated with a number of medical and psychiatric outcomes. However, the reported effects that specific childhood adversities have on suicidality vary across studies. Method This was a cross-sectional, stratified, multistage area probability investigation of a general population in Brazil, designated the São Paulo Megacity Mental Health Survey. The World Mental Health Composite International Diagnostic Interview was applied in 5037 individuals ≥ 18 years of age, in order to assess 12 different adversities occurring during childhood and/or adolescence, as well as to look for associations between those adversities and subsequent suicidality in different age strata. Results Over half of the respondents reported at least one childhood adversity. Only physical abuse was consistently associated with suicide attempts in all subsequent life stages (OR = 2.1). Among adults 20–29 years of age, the likelihood of a suicide attempt was correlated with parental divorce, whereas suicidal ideation was associated with prior sexual abuse. Among adults over 30 years of age, physical illness and economic adversity emerged as relevant childhood adversities associated with suicide attempts, whereas sexual abuse, family violence, and economic adversity were associated with suicidal ideation. Conclusion Childhood adversities, especially physical abuse, are likely associated with unfavorable consequences in subsequent years. For suicidality across a lifespan, the role of different childhood adversities must be examined independently.
Mkk4 Is a Negative Regulator of the Transforming Growth Factor Beta 1 Signaling Associated With Atrial Remodeling and Arrhythmogenesis With Age

Background Atrial fibrillation (AF), often associated with structural, fibrotic change in cardiac tissues involving regulatory signaling mediators, becomes increasingly common with age. In the present study, we explored the role of mitogen‐activated protein kinase kinase 4 (Mkk4), a critical component of the stress‐activated mitogen‐activated protein kinase family, in age‐associated AF. Methods and Results We developed a novel mouse model with a selective inactivation of atrial cardiomyocyte Mkk4 (Mkk4ACKO). We characterized and compared electrophysiological, histological, and molecular features of young (3‐ to 4‐month), adult (6‐month), and old (1‐year) Mkk4ACKO mice with age‐matched control littermates (Mkk4F/F). Aging Mkk4ACKO mice were more susceptible to atrial tachyarrhythmias than the corresponding Mkk4F/F mice, showing characteristic slow and dispersed atrial conduction, for which modeling studies demonstrated potential arrhythmic effects. These differences paralleled increased interstitial fibrosis, upregulated transforming growth factor beta 1 (TGF‐β1) signaling and dysregulation of matrix metalloproteinases in Mkk4ACKO, compared to Mkk4F/F, atria. Mkk4 inactivation increased the sensitivity of cultured cardiomyocytes to angiotensin II–induced activation of TGF‐β1 signaling. This, in turn, enhanced expression of profibrotic molecules in cultured cardiac fibroblasts, suggesting cross‐talk between these two cell types in profibrotic signaling. Finally, human atrial tissues in AF showed a Mkk4 downregulation associated with increased production of profibrotic molecules, compared to findings in tissue from control subjects in sinus rhythm. Conclusions These findings together demonstrate, for the first time, that Mkk4 is a negative regulator of the TGF‐β1 signaling associated with atrial remodeling and arrhythmogenesis with age, establishing Mkk4 as a new potential therapeutic target for treating AF.
Proposed Diagnostic Criteria for Chronic Antibody‐Mediated Rejection in Liver Allografts

Donor‐specific alloantibodies (DSA) can cause acute antibody‐mediated rejection (AMR) in all solid organ allografts. However, long‐term outcome in patients with posttransplant DSA needs further study. We retrospectively evaluated prospectively collected paired serum, tissue, and data on 45 matched DSA− positive [DSA+; mean florescence intensity (MFI) ≥10 000] and ‐negative (DSA−) recipients of a primary liver‐only allograft from January 2000 to April 2009. Blinded histopathologic evaluation demonstrated that DSA+ versus DSA− patients were more likely to have subtle inflammation and unique patterns of fibrosis, despite normal or near‐normal liver function tests. Stepwise multivariable modeling developed a score (putatively named the chronic AMR [cAMR] score) that included interface activity, lobular inflammation, portal tract collagenization, portal venopathy, sinusoidal fibrosis, and hepatitis C virus status. The score was developed (c = 0.811) and cross‐validated (c = 0.704) to predict allograft failure. Two cutoffs were employed to optimize sensitivity and specificity (80% each); a value >27.5 predicted 50% 10‐year allograft failure. We propose chronic AMR as a potential new entity defined by (1) a high cAMR score, (2) DSA, and (3) elimination of other potential causes of a similar injury pattern. In conclusion, cAMR score calculation identified liver allograft recipients with DSA at highest risk for allograft loss, although independent validation is needed.
Twenty years of research into Chlamydia-like organisms: a revolution in our understanding of the biology and pathogenicity of members of the phylum Chlamydiae.

Chlamydiae are obligate intracellular bacteria that share a unique but remarkably conserved biphasic developmental cycle that relies on a eukaryotic host cell for survival. Although the phylum was originally thought to only contain one family, the Chlamydiaceae, a total of nine families are now recognized. These so-called Chlamydia-like organisms (CLOs) are also referred to as 'environmental chlamydiae', as many were initially isolated from environmental sources. However, these organisms are also emerging pathogens, as many, such as Parachlamydia sp. , Simkania sp. and Waddlia sp. , have been associated with human disease, and others, such as Piscichlamydia sp. and Parilichlamydia sp. , have been documented in association with diseases in animals. Their strict intracellular nature and the requirement for cell culture have been a confounding factor in characterizing the biology and pathogenicity of CLOs. Nevertheless, the genomes of seven CLO species have now been sequenced, providing new information on their potential ability to adapt to a wide range of hosts. As new isolation and diagnostic methods advance, we are able to further explore the richness of this phylum with further research likely to help define the true pathogenic potential of the CLOs while also providing insight into the origins of the 'traditional' chlamydiae.
Neuronal Synchronization in Human Posterior Parietal Cortex during Reach Planning

Although single-unit studies in monkeys have identified effector-related regions in the posterior parietal cortex (PPC) during saccade and reach planning, the degree of effector specificity of corresponding human regions, as established by recordings of the blood oxygen level-dependent signal, is still under debate. Here, we addressed this issue from a different perspective, by studying the neuronal synchronization of the human PPC during both reach and saccade planning. Using magnetoencephalography (MEG), we recorded ongoing brain activity while subjects performed randomly alternating trials of memory-guided reaches or saccades. Additionally, subjects performed a dissociation task requiring them to plan both a memory-guided saccade and reach to locations in opposing visual hemifields. We examined changes in spectral power of the MEG signal during a 1.5 s memory period in relation to target location (left/right) and effector type (eye/hand). The results show direction-selective synchronization in the 70–90 Hz gamma frequency band, originating from the medial aspect of the PPC, when planning a reaching movement. In contrast, activity in a more central portion of the PPC was synchronized in a lower gamma band (50–60 Hz) when planning the direction of a saccade. Both observations were corroborated in the dissociation task. In the lower frequency bands, we observed sustained alpha-band (8–12 Hz) desynchronization in occipitoparietal regions, but in an effector-unspecific manner. These results suggest that distinct modules in the posterior parietal cortex encode movement goals of different effectors by selective gamma-band activity, compatible with the functional organization of monkey PPC.
Efficiency of Private Household Sand Filters in Removing Nutrients and Microbes from Wastewater in Finland

Sand filters have been shown to be an economic and effective solution for wastewater treatment in private households, although the removal of phosphorus (P) may be insufficient. However, P removal can be improved by adding a P-adsorbing material, such as biotite, into the sand filters. The physico-chemical characteristics and the microbial quality of the effluents of family-scale sand filters without adsorbing media (SF), sand filters with a biotite layer (B), and sand filters with a modular filter (MB) were followed for one year. Sand filters with a biotite layer displayed the highest capacity to remove nitrogen (N) and biological oxygen demand BOD7. The efficiency of these filters did not depend on the age of the filter or the season. The P load of the effluent did not differ between sand filters with and without a biotite layer, but the modular sand filter failed to adequately reduce P. The treatment efficiency of sand filters without biotite decreased with increasing age. These private household sand filters can be a good way to treat domestic wastewaters, since these generally comply with the minimum requirements of a Finnish Decree (157/2017). However, enteric viruses (noro- and adenoviruses) were commonly found in the effluents, and the numbers of Escherichia coli were often above 103 colony forming units (CFU) 100 mL−1 (limit for the the EU Bathing Water Directive 2006/7/EC) for good water quality), signifying a risk of microbial contamination of nearby drinking water wells, as well as bathing and irrigation waters.
The Four‐Domain Development Diagram: A Guide for Holistic Design of Effective Learning Experiences for the Twenty‐first Century Engineer

The twenty‐first century challenges engineering educators to design learning experiences to strategically and holistically target students' development, including cognitive, psychomotor, social and affective domains. We propose a guide for the design process. The Four‐Domain Development Diagram (4DDD) is a synthesis of learning theory and empirical data. This guide maps the relationships among the major factors that influence learning and presents them in the form of a causal loop diagram, a tool used by systems dynamicists to show how changes in important factors affect other factors within the system. In this paper, we present the theoretical and empirical basis of the 4DDD. We also describe how the 4DDD can be used as a design guide for instructional changes that promote more effective learning experiences for the broader cognitive, social, affective, and psychomotor development required of today's engineering graduate.
Treatment of respiratory insufficiency in Duchenne's muscular dystrophy: nasal ventilation in the initial stages.

Fourteen patients with Duchenne's muscular dystrophy (DMD) received nasal ventilation at the beginning of the declining phase of their vital capacity (VC). At that point, the mean value (SD) of their vital capacity was 1,756 (363) mL notably inferior to the predicted values. Nasal ventilation was performed according to a precise protocol, with an average nocturnal duration of 8 h. The annual decline of vital capacity was about 70 ml, showing a significant reduction compared with the value of 200 mL.yr-1 of untreated patients. Follow-up of treated patients (3.8 yrs; SD 1.9 yrs) has enabled us to distinguish different groups of results with useful practical consequences. In 29% of cases, the initial progression of decline of vital capacity was poorly modified by the treatment. In 71% of patients, the decline of VC was significantly decreased. In 35% of cases tracheal ventilation followed nasal ventilation. The normal mortality rate of DMD has greatly changed as a result of this method.
Can we be both resilient and well, and what choices do people have? Incorporating agency into the resilience debate from a fisheries perspective.

In the midst of a global fisheries crisis, there has been great interest in the fostering of adaptation and resilience in fisheries, as a means to reduce vulnerability and improve the capacity of fishing society to adapt to change. However, enhanced resilience does not automatically result in improved well-being of people, and adaptation strategies are riddled with difficult choices, or trade-offs, that people must negotiate. This paper uses the context of fisheries to explore some apparent tensions between adapting to change on the one hand, and the pursuit of well-being on the other, and illustrates that trade-offs can operate at different levels of scale. It argues that policies that seek to support fisheries resilience need to be built on a better understanding of the wide range of consequences that adaptation has on fisher well-being, the agency people exert in negotiating their adaptation strategies, and how this feeds back into the resilience of fisheries as a social-ecological system. The paper draws from theories on agency and adaptive preferences to illustrate how agency might be better incorporated into the resilience debate.
Maternal UNC-45 is involved in cytokinesis and colocalizes with non-muscle myosin in the early Caenorhabditis elegans embryo

The Caenorhabditis elegans UNC-45 protein contains tetratricopeptide repeats and a domain with similarity to fungal proteins, and it differentially colocalizes with myosin heavy chain B in the body wall muscles of adult worms. Although it is essential for normal myosin filament assembly in body wall muscle development, strong mutants show a previously unexplained maternal effect. We show here that the UNC-45 protein is maternally contributed and is present in all cells of the early embryo whereas zygotic UNC-45 expression is only detected in the developing muscle cells. Embryos produced from adults with reduced germline expression of UNC-45 exhibit cytokinesis defects suggesting that UNC-45 has a novel role in the early embryo in addition to muscle development. Yeast two-hybrid screens show that UNC-45 can directly interact with NMY-2, a non-muscle type II myosin, and UNC-45 and NMY-2 colocalize at cell boundaries in early embryos. Localization of UNC-45 at these boundaries is dependent upon the presence of NMY-2. Our results suggest that UNC-45 interacts with more than one type of myosin and functions in the embryo to regulate cytoplasmic myosin assembly and/or stability during cytokinesis.
Glutathione S-Transferase Interacting with Far-Red Insensitive 219 Is Involved in Phytochrome A-Mediated Signaling in Arabidopsis 1(W)(OA)

Far-red (FR) insensitive 219 (FIN219) was previously shown to be involved in phytochrome A-mediated FR light signaling. To further understand its function and regulatory relation with other light-signaling components, a yeast two-hybrid approach was used to isolate FIN219-interacting partners. Here, we demonstrate that FIN219-interacting protein 1 (FIP1) interacts with FIN219 in vitro and in vivo and is composed of 217 amino acids that belong to the tau class of the large glutathione S-transferase gene family. FIP1 was further shown to have glutathione S-transferase activity. The gain offunction and partial loss of function of FIP1 resulted in a hyposensitive hypocotyl phenotype under continuous FR (cFR) light and a delayed flowering phenotype under long-day conditions, which suggests that FIP1 may exist in a complex to function in the regulation of Arabidopsis (Arabidopsis thaliana) development. In addition, FIP1 mRNAwas down-regulated in the suppressor of phytochrome A-105 1 mutant and differentially expressed in constitutive photomorphogenic 1-4 (cop1-4) and cop1-5 mutants under cFR. Intriguingly, FIP1 expression was up-regulated in the fin219 mutant under all light conditions, except cFR. Furthermore, promoter activity assays revealed that FIP1 expression was light dependent, mainly associated with vascular tissues, and developmentally regulated. Subcellular localization studies revealed that the b-glucuronidase-FIP1 fusion protein was localized in the nucleus and cytoplasm. Taken together, these data indicate that FIP1 may interact with FIN219 to regulate cell elongation and flowering in response to light.