Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of diagnostic ultrasound use in a breast cancer detection strategy in Northern Peru

To evaluate the diagnostic impact of point-of-care breast ultrasound by trained primary care physicians (PCPs) as part of a breast cancer detection program using clinical breast exam in an underserved region of Peru. Medical records and breast ultrasound images of symptomatic women presenting to the Breast Cancer Detection Model (BCDM) in Trujillo, Peru were collected from 2017–2018. Performance was measured against final outcomes derived from regional cancer center medical records, fine needle aspiration results, patient follow-up (sensitivity, specificity, positive, and negative predictive values), and by percent agreement with the retrospective, blinded interpretation of images by a fellowship-trained breast radiologist, and a Peruvian breast surgeon. The diagnostic impact of ultrasound, compared to clinical breast exam (CBE), was calculated for actual practice and for potential impact of two alternative reporting systems. Of the 171 women presenting for breast ultrasound, 23 had breast cancer (13.5%). Breast ultrasound used as a triage test (current practice) detected all cancer cases (including four cancers missed on confirmatory CBE). PCPs showed strong agreement with radiologist and surgeon readings regarding the final management of masses (85.4% and 80.4%, respectively). While the triage system yielded a similar number of biopsies as CBE alone, using the condensed and full BI-RADS systems would have reduced biopsies by 60% while identifying 87% of cancers immediately and deferring 13% to six-month follow-up. Point-of-care ultrasound performed by trained PCPs improves diagnostic accuracy for managing symptomatic women over CBE alone and enhances access. Greater use of BI-RADS to guide management would reduce the diagnostic burden substantially.
Tridentate 3-Substituted Naphthoquinone Ruthenium Arene Complexes: Synthesis, Characterization, Aqueous Behavior, and Theoretical and Biological Studies

A series of nine RuII arene complexes bearing tridentate naphthoquinone-based N,O,O-ligands was synthesized and characterized. Aqueous stability and their hydrolysis mechanism were investigated via UV/vis photometry, HPLC-MS, and density functional theory calculations. Substituents with a positive inductive effect improved their stability at physiological pH (7.4) intensely, whereas substituents such as halogens accelerated hydrolysis and formation of dimeric pyrazolate and hydroxido bridged dimers. The observed cytotoxic profile is unusual, as complexes exhibited much higher cytotoxicity in SW480 colon cancer cells than in the broadly chemo- (incl. platinum-) sensitive CH1/PA-1 teratocarcinoma cells. This activity pattern as well as reduced or slightly enhanced ROS generation and the lack of DNA interactions indicate a mode of action different from established or previously investigated classes of metallodrugs.
DeepR2cov: deep representation learning on heterogeneous drug networks to discover anti-inflammatory agents for COVID-19

Abstract Recent studies have demonstrated that the excessive inflammatory response is an important factor of death in coronavirus disease 2019 (COVID-19) patients. In this study, we propose a deep representation on heterogeneous drug networks, termed DeepR2cov, to discover potential agents for treating the excessive inflammatory response in COVID-19 patients. This work explores the multi-hub characteristic of a heterogeneous drug network integrating eight unique networks. Inspired by the multi-hub characteristic, we design 3 billion special meta paths to train a deep representation model for learning low-dimensional vectors that integrate long-range structure dependency and complex semantic relation among network nodes. Based on the representation vectors and transcriptomics data, we predict 22 drugs that bind to tumor necrosis factor-α or interleukin-6, whose therapeutic associations with the inflammation storm in COVID-19 patients, and molecular binding model are further validated via data from PubMed publications, ongoing clinical trials and a docking program. In addition, the results on five biomedical applications suggest that DeepR2cov significantly outperforms five existing representation approaches. In summary, DeepR2cov is a powerful network representation approach and holds the potential to accelerate treatment of the inflammatory responses in COVID-19 patients. The source code and data can be downloaded from https://github.com/pengsl-lab/DeepR2cov.git.
Vaccines and Disease Relapses in Children with Nephrotic Syndrome.

More than half of children with idiopathic nephrotic syndrome develop frequent relapses or steroid depen-dence and require chronic use of immune suppres-sants, such as cyclosporin, mycophenolate mofetil, or B cell – depleting therapies, to maintain disease in remission (1). Loss of endogenous antibodies in the nephrotic urines and pharmacologic immune suppres-sion contribute to a higher risk for upper respiratory viral infections and in ﬂ uenza in children with steroid-dependent nephrotic syndrome. These infectious episodes may cause or induce relapse of nephrotic syndrome.Thisformed the background for the 2012 Kidney Disease Improving Global Outcomes guidelines that recommend pneumococcal, annual in ﬂ uenza, and inactivated vaccines, whereas they contraindicate live attenuated vaccines (measles, mumps, rubella, varicel-la, rotavirus, and yellow fever), especially in patients on immunosuppressive or cytotoxic agents (2). Patho-genic mechanisms of nephrotic syndrome are still not fully elucidated, but increasing evidence points at a dysregulation of the immune system, involving both B and T cells. This also raises the intriguing hypothesis that vaccines, by eliciting an immune response, promote disease relapses (3). Overall, previous retrospective analysis reported that in ﬂ uenza virus vaccination in children with nephrotic syndrome is not associated with a higher risk of relapse (4).
The morphology control of polyaniline as conducting polymer in fuel cell technology

Electrically conducting polymers described as a new class of 'synthetic metals' reached a high interest in the last years, confirmed by the 2000 Nobel Prize in chemistry for the discovery and development of conductive polymers (Alan J. Heeger, Alan G. MacDiarmid and Hideki Shirakawa). The most commonly studied classes of conducting polymer were: polyacetylene, polytiophene, polypyrole, polyaniline and derivates, being investigated as conducting matrices for electrocatalytic applications. Among them, polyaniline (PANI) is one of the most studied materials because of its high conductivity upon doping with acids (10 -10 2 S/cm), well behaved electrochemistry, and easy preparation under reproducible conditions by both electro - polymerization and chemically oxidation of aniline, chemical and electrical stability and good environmental stability. The purpose of our research is to obtain a conductive and stable polymer, with a high surface area, by variation of different preparation techniques and parameters, in sense of polymer morphology control. The research interest is to implement the conducting polymers in fuel cell technology, as Membrane Electrode Assembly (MEA) components or conducting supports for noble metal deposition.
EFFECT OF DIFFERENT MECHANICAL VIBRATION ON BLOOD PARAMETERS OF ONE DAY OLD BROILER CHICKEN

Mechanical vibrations are congenital to any system of transportation. In poultry industry, the higher or lower intensity of this agent during the transportation of eggs and chickens can increase the production losses and decrease the efficiency of the system as a whole. This study was carried out to investigate the effects of mechanical vibration (MV) generated by mechanized equipment on eggs, chickens mortality and levels of some blood biochemicals (triglyceride, glucose, cholesterol, calcium, phosphorus, urea) were analyzed in one days chickens. The data showed that the glucose and urea concentrations in blood of one day old chicks and their mortality increased with increasing vibration levels but calcium, cholesterol and triglyceride levels decreased. Levels of vibration seemed not to affect all of parameters. Mechanical vibrations may be responsible for the incidence of cracks, in addition to promoting the agitation of internal constituents (yolk and albumen), which could potentially compromise the quality of birth and hatchlings. The mechanical vibration are related to stress, discomfort and depreciation of the welfare of the birds, changed in glucose and corticosteroids levels and thus affect other factors as well as the quality of the meat. Keywords : Glucose, Cholesterol, Triglyceride, Calcium, Phosphorus, Urea, Mortality, Broiler chick, Mechanical vibration
Correction

BIOCHEMISTRY Correction for “Mutations in the linker domain affect phosphoSTAT3 function and suggest targets for interrupting STAT3 activity,” by Claudia Mertens, Bhagwattie Haripal, Sebastian Klinge, and James E. Darnell, which appeared in issue 48, December 1, 2014, of Proc Natl Acad Sci USA (112:14811–14816; first published November 9, 2015; 10.1073/pnas.1515876112). The authors note that on the sixth page of the article, right column, third full paragraph, line 1, “we learned that the compound described” should instead have appeared as “we learned from a private confidential communication that the compound described. ” The online version has been corrected. www.pnas. org/cgi/doi/10.1073/pnas.1522662112
Bee foraging preferences, microbiota and pathogens revealed by direct shotgun metagenomics of honey

Honeybees (Apis mellifera) continue to succumb to human and environmental pressures despite their crucial role in providing essential ecosystem services. Owing to their foraging and honey production activities, honeybees form complex relationships with species across all domains, such as plants, viruses, bacteria (symbiotic and pathogenic), and other hive pests, making honey a valuable biomonitoring tool for assessing their ecological niche. Thus, the application of honey shotgun metagenomics (SM) has paved the way for a detailed description of the species honeybees interact with, in order to better assess the multiple factors governing their health. Here, we describe the implementation of optimized honey DNA extraction methodology coupled to direct shotgun metagenomics (Direct-SM) analysis, and to a computationally optimised and validated pipeline for taxonomic classification of species detected in honey. By comparing honey collected across 3 harvesting seasons in a stable apiary, we show that Direct-SM can describe the variability of sampled plant species, revealing honeybee behavioural adaptation. In addition, we reveal that Direct-SM can non-invasively capture the diversity of species comprising the core and non-core bacterial communities of the gut microbiome. Finally, we show that this methodology is applicable for the monitoring of pathogens and particularly for the biomonitoring varroa infestation. These results suggest that Direct-SM can accurately and comprehensively describe honeybee ecological niches and can be deployed to assess bee health in the field.
A Comprehensive Model of Glucose-Insulin Regulation Including Acute and Prolonged Effects of Physical Activity in Type 1 Diabetes

Objective For type 1 diabetic patients, accurate adjustment of insulin treatment to physical activity (PA) is a challenging open problem. Glucose uptake by the exercising muscles increases acutely, causing increased hepatic glucose production to maintain glucose homeostasis. Meanwhile, insulin sensitivity is elevated for a prolonged period to drive glycogen repletion during recovery. These processes strongly depend on PA duration and intensity, making their combined effects difficult to predict accurately. In this work, we develop a model of glucose-insulin regulation that captures PA from low to high intensity including acute and prolonged effects on glucose metabolism. Methods We extended an existing minimal model of glucose-insulin regulation to capture PA-driven changes in glucose metabolism. We incorporated the insulin-independent increase in glucose uptake and production, including the effects of glycogen depletion and of high-intensity PA on production. The model also captures the prolonged increase in insulin sensitivity. Results The model accurately predicts glucose dynamics of published data during short and prolonged PA of moderate to high intensity and during subsequent recovery. In-silico full-day studies elucidate the effects of timing, duration and intensity of PA and of insulin bolus reduction on glucose levels during and after the activity. Conclusion The proposed model captures the blood glucose dynamics during all main PA regimes. Significance Mathematical models of glucose-insulin regulation are critical components of closed-loop insulin delivery and clinical decision support systems for achieving good glycemic control. The presented model shows potential for the development and assessment of algorithms targeting treatment adjustment to PA.
All-optical mechanobiology interrogation of YAP in human cancer and normal cells using a novel multi-functional system

Long-term multi-functional imaging and analysis of live cells require streamlined functional coordination of various hardware and software platforms. However, manual control of various equipment produced by different manufacturers is labor-intensive and time-consuming, potentially decreasing the accuracy, reproducibility, and quality of acquired data. Therefore, an all-in-one and user-programmable system that enables automatic, multi-functional, and long-term image acquisition and is compatible with most fluorescent microscopy platforms can desirably benefit the scientific community. In this paper, we introduce the full operating protocols of utilizing a novel integrated software system that consists of (1) a home-built software program, titled “Automatic Multi-functional Integration Program (AMFIP)”, which enables automatic multi-channel imaging acquisition, and (2) a suite of quantitative imaging analysis and cell traction computation packages. We applied this integrated system to reveal the previously unknown relationship between the spatial-temporal distribution of mechano-sensitive Yes-associated protein (YAP) and the cell mechanics, including cell spreading and traction, in human normal cells (B2B) and lung cancer cells (PC9). Leveraging our system’s capability of multi-channel control and readout, we found: (1) B2B normal cells and PC9 cancer cells show distinct YAP expression, traction, and cell dynamics relationship during cell spreading and migration processes; and (2) PC9 cancer cells apply noticeable peri-nuclear forces on substrates. In summary, this paper presents a detailed stepwise protocol on how to utilize an integrated user-programmable system that enables automatic multi-functional imaging and analysis to elucidate YAP mechanosensitivity. These tools open the possibility for detailed explorations of multifaceted signaling dynamics in the context of cell physiology and pathology. SUMMARY This paper presents a detailed stepwise protocol on how to utilize an integrated user-programmable system that enables all-optical electro-mechanobiology interrogation to elucidate YAP mechanosensitivity.
Bipolar-associated miR-499-5p controls neuroplasticity by downregulating the Cav1.2 L-type voltage gated calcium channel subunit CACNB2

Bipolar disorder (BD) is a chronic mood disorder characterized by alternating manic and depressive episodes, often in conjunction with cognitive deficits. Dysregulation of neuroplasticity and calcium homeostasis as a result of complex genetic environment interactions are frequently observed in BD patients, but the underlying molecular mechanisms are largely unknown. Here, we show that a BD-associated microRNA, miR-499-5p, regulates neuronal dendrite development and cognitive function by downregulating the BD risk gene CACNB2. miR-499-5p expression is increased in peripheral blood of BD patients and healthy subjects at risk of developing the disorder due to a history of childhood maltreatment. This up-regulation is paralleled in the hippocampus of rats which underwent juvenile social isolation. Elevating miR-499-5p levels in rat hippocampal pyramidal neurons impairs dendritogenesis and reduces surface expression and activity of the voltage-gated L-type calcium channel Cav1.2. We further identified CACNB2, which encodes a regulatory β-subunit of Cav1.2, as a direct target of miR-499-5p in neurons. CACNB2 downregulation is required for the miR-499-5p dependent impairment of dendritogenesis, suggesting that CACNB2 is an important downstream target of miR-499-5p in the regulation of neuroplasticity. Finally, elevating miR-499-5p in the hippocampus in vivo is sufficient to induce short-term memory impairments in rats haploinsufficient for the Cav1.2 pore forming subunit Cacna1c. Taken together, we propose that stress-induced upregulation of miR-499-5p contributes to dendritic impairments and deregulated calcium homeostasis in BD, with specific implications for the neurocognitive dysfunction frequently observed in BD patients.
Right Temporoparietal Junction Encodes Mental Experience of Others More Than Evaluating False Versus True Belief

When people make inferences about other people’s minds, called theory of mind (ToM), a network in the cerebral cortex becomes active. ToM experiments sometimes use the false belief task, in which subjects decide whether a story character believes A or B. The “false” belief occurs if the character believes A when B is true. We devised a version in which subjects judged whether a cartoon head “believed” a ball to be in box 1 or box 2. The task was a visual, reaction-time version of a ToM task. We proposed two alternative hypotheses. In hypothesis 1, cortical regions of interest within the ToM network should distinguish between false and true belief trials, reflecting outside information that the subjects have about the cartoon character. In hypothesis 2, the ToM network should distinguish between conditions only if the subjects think that the cartoon character can distinguish between the conditions, thus reflecting a model of the internal contents of the cartoon character’s mind. The results supported hypothesis 2. Events that the cartoon could not “see” did not affect activity in the ToM network; the same events, when the cartoon could apparently “see” them, significantly affected activity in the right temporoparietal junction (TPJ). The results support the view that the right TPJ participates in modeling the mental states of others, rather than in evaluating the accuracy of the beliefs of others, and may help explain why previous experiments showed mixed results when directly comparing false belief to true belief conditions. Significance statement How do we understand the minds of others? A specific network of areas in the human brain is known to emphasize building models of other people’s minds. In one traditional hypothesis, this network helps us distinguish whether someone else’s beliefs are true or false. Here we show that the network is relatively insensitive to one’s own, outside knowledge about whether someone else’s beliefs are true or false. Instead, at least one node in the network appears to limit itself mainly to reconstructing the other person’s point of view. This social cognition network may be more about empathy than about critical evaluation. Classification Social Sciences - Psychological and Cognitive Sciences
Effect of different methods and rates of phosphorus application in mungbean

Poor performance of fertilizer phosphorus is one of the major causes depressing the productivity of the crops. An investigation was, therefore, carried out under field conditions to compare the relative efficacy of broadcast, banding and fertigation technique for improving P use efficiency in mungbean. The response to P applied through fertigation was more pronounced as compared to broadcast and banding method. Significantly highest mungbean yield, P uptake, P recoveries and agronomic efficiency were recorded with fertigation and the lowest with broadcast method. The low rate of P application resulted in a relatively higher P recovery and agronomic efficiency compared to higher rate of P application by either method.
The mitotic checkpoint protein MAD2 delivers monoamine transporters to endocytosis

Monoamine transporters retrieve serotonin (SERT), dopamine (DAT) and norepinephrine (NET) from the synaptic cleft. Surface levels of transporters are also regulated by internalization. Clathrin-mediated endocytosis of cargo proteins requires adaptor protein 2 (AP2), which recruits cargo to the nascent clathrin-cage. The transporter C-terminus is required for internalization but lacks an AP2-binding site. In the present work, we show that internalization of SERT and DAT relies on MAD2, a protein of the mitotic spindle assembly checkpoint (SAC). A MAD2-interaction motif in the transporter C-terminus interacts with MAD2. This binding is contingent on the closed conformation of MAD2 and allowed for the recruitment of two additional SAC proteins, BubR1 and p31COMET as well as AP2. MAD2, BubR1 and p31COMET are present in serotoninergic neurons of the dorsal raphe, corroborating a biological role of the identified interactions. Depletion of MAD2 in HEK-293 cells stably expressing SERT and DAT decreases constitutive and triggered endocytosis, respectively. Altogether, our study describes a candidate mechanism, which connects monoamine transporters to the endocytic machinery and thus supports their internalization.
Selective sweeps influence diversity over large regions of the mouse genome

To what extent do substitutions in protein-coding versus gene-regulatory regions contribute to fitness change over time? Answering this question requires estimates of the extent of selection acting on beneficial mutations in the two classes of sites. New mutations that have advantageous or deleterious fitness effects can induce selective sweeps and background selection, respectively, causing variation in the level of neutral genetic diversity along the genome. In this study, we analyse the profiles of genetic variability around protein-coding and regulatory elements in the genomes of wild mice to estimate the parameters of positive selection. We find patterns of diversity consistent with the effects of selection at linked sites, which are similar across mouse taxa, despite differences in effective population size and demographic history. By fitting a model that combines the effects of selective sweeps and background selection, we estimate the strength of positive selection and the frequency of advantageous mutations. We find that strong positive selection is required to explain variation in genetic diversity across the murid genome. In particular, we estimate that beneficial mutations in protein-coding regions have stronger effects on fitness than do mutations in gene-regulatory regions, but that mutations in gene-regulatory regions are more common. Overall though, our parameter estimates suggest that the cumulative fitness changes brought about by beneficial mutations in protein-coding may be greater than those in gene-regulatory elements.
Ramp compression of tantalum to 330 GPa

We report on the stress–density and rate-dependent response for Ta, ramp compressed to 330 GPa with strain rates up to 5 × 108 s−1. We employ temporally shaped laser drives to compress Ta stepped foils over several to tens of nanoseconds. Lagrangian wave-profile analysis reveals a stress–density relationship which falls below the Hugoniot, above the hydrostat, and is consistent with ramp-compression experiments at lower strain rates. We also report on the peak elastic stress prior to plastic deformation as a function of strain rate for laser-driven ramp and shock-compression data spanning the 1–50 × 107 s−1 strain-rate range. When combined with previously published lower strain data (101–107 s−1), we observe a change in rate dependence, suggesting a transition from thermally activated to defect-limited (phonon drag) dislocation motion occurring at a strain rate of about 105 s−1.