Miracle-dz/UniFAR-FTUs huggingface dataset:
Evidence of a developmental origin for β-cell heterogeneity using a dual lineage-tracing technology

ABSTRACT The Cre/loxP system has been used extensively in mouse models with a limitation of one lineage at a time. Differences in function and other properties among populations of adult β-cells is termed β-cell heterogeneity, which was recently associated with diabetic phenotypes. Nevertheless, the presence of a developmentally derived β-cell heterogeneity is unclear. Here, we have developed a novel dual lineage-tracing technology, using a combination of two recombinase systems, Dre/RoxP and Cre/LoxP, to independently trace green fluorescent Pdx1-lineage cells and red fluorescent Ptf1a-lineage cells in the developing and adult mouse pancreas. We detected a few Pdx1+/Ptf1a− lineage cells in addition to the vast majority of Pdx1+/Ptf1a+ lineage cells in the pancreas. Moreover, Pdx1+/Ptf1a+ lineage β-cells had fewer Ki-67+ proliferating β-cells, and expressed higher mRNA levels of insulin, Glut2, Pdx1, MafA and Nkx6.1, but lower CCND1 and CDK4 levels, compared with Pdx1+/Ptf1a− lineage β-cells. Furthermore, more TSQ-high, SSC-high cells were detected in the Pdx1+Ptf1a+ lineage population than in the Pdx1+Ptf1a− lineage population. Together, these data suggest that differential activation of Ptf1a in the developing pancreas may correlate with this β-cell heterogeneity. Summary: Using a novel dual lineage-tracing technology (Dre/RoxP and Cre/LoxP), differential activation of Ptf1a in the developing pancreas is revealed to potentially correlate with β-cell heterogeneity.
Robust repression of tRNA gene transcription during stress requires protein arginine methylation

This work examines how protein arginine methylation of Rpc31, a subunit of RNA Pol III, promotes negative regulation of tRNA biogenesis in the context of cellular stress. Protein arginine methylation is an important means by which protein function can be regulated. In the budding yeast, this modification is catalyzed by the major protein arginine methyltransferase Hmt1. Here, we provide evidence that the Hmt1-mediated methylation of Rpc31, a subunit of RNA polymerase III, plays context-dependent roles in tRNA gene transcription: under conditions optimal for growth, it positively regulates tRNA gene transcription, and in the setting of stress, it promotes robust transcriptional repression. In the context of stress, methylation of Rpc31 allows for its optimal interaction with RNA polymerase III global repressor Maf1. Interestingly, mammalian Hmt1 homologue is able to methylate one of Rpc31’s human homologue, RPC32β, but not its paralogue, RPC32α. Our data led us to propose an efficient model whereby protein arginine methylation facilitates metabolic economy and coordinates protein-synthetic capacity.
Development of a Standardized Grading Scale for Atherosclerotic Disease of the Head and Neck.

OBJECTIVE For research and risk factor analysis, a reproducible method quantifying atherosclerosis is necessary. Our aim was to develop a computed tomography (CT) angiography grading system to quantify atherosclerotic disease of the head and neck. METHODS Institutional review board-approved, retrospective analysis was performed on 152 patients who underwent head/neck CT angiography. A grading scale was designed to calculate plaque burden at multiple sites with the sum referred to as atherosclerosis score. Three radiologists calculated scores with an overlap of cases to calculate the intraclass correlation coefficient. RESULTS Without any prior training, the intraclass correlation coefficient between readers was considered fair. After a short tutorial, intraclass correlation coefficient was recalculated using separate patients, showing excellent correlation.Statistically significant positive correlation was found between atherosclerosis scale and age, hyperlipidemia, hypertension, and diabetes, but no correlation with sex or smoking status. CONCLUSIONS A simple, visual grading scale for atherosclerosis in head/neck CT angiography was used to standardize reporting and better characterize a patient's risk of stroke.
2D analytical potential modeling of junctionless DG MOSFETs in subthreshold region including proposal for calculating the threshold voltage

We derived an analytical two-dimensional model to calculate the potential within ultra-scaled junctionless double-gate MOSFETs (DG MOSFETs) valid in subthreshold region. We propose an approach how to calculate the threshold voltage of such devices, and present our first results. Compared to conventional MOSFETs, the proposed junctionless transistor has no pn-junctions. Its type of doping in the channel region is the same as in the source/drain. The device is turned on by creating a conducting channel in the center of the silicon, and turned off by depleting it. To ensure a safe switching behavior, the investigation of the subthreshold region is therefore important. A Comparison of our model with numerical simulation results confirms its validity for ultra-scaled devices having a channel length about 22 nm.
Exposure to Fine Particulate Matter and Ovarian Reserve Among Women from a Fertility Clinic.

BACKGROUND An increasing number of studies have linked air pollution to decreased fertility. Whether this is due to an effect on ovarian reserve is unknown. METHOD Our study included 632 women attending the Massachusetts General Hospital Fertility Center (2004-2015) who had a measured antral follicle count. Validated spatiotemporal models estimated daily particulate matter <2.5 µg/m (PM2.5) (based on residential address) for the 3 months before the antral follicle count. We analyzed associations with Poisson regression. RESULTS Every 2 µg/m increase in estimated PM2.5 exposure was associated with a -7.2% (95% confidence interval = -10.4%, -3.8%) lower antral follicle count adjusting for age, body mass index, smoking status, and year and season of the count. The association of PM2.5 with antral follicle count was stronger among women with female factor infertility (-16.3% per 2 µg/m). CONCLUSIONS Among women from an infertility clinic, higher PM2.5 exposure was associated with lower ovarian reserve, raising concern that air pollution may accelerate reproductive aging.
Needleless intradermal vaccination for foot-and-mouth disease induced granuloma-free effective protection in pigs

Vaccination is one of the most effective ways of controlling and preventing foot-and-mouth disease (FMD) outbreaks. The effective prevention of this disease requires the use of high-quality vaccines to meet the criteria that enable customers to use them simply. The administration of FMD vaccines containing oil-based adjuvants in pigs can induce the formation of granuloma in the muscle of the vaccinated, which makes these vaccines a less preferable option. Therefore, it is important to establish an FMD vaccine and vaccine delivery tool that offers better immunity and safer application. This study compared the immune responses of intramuscular and needleless intradermal vaccination in pigs. When the same amount of an FMD virus (FMDV) antigen was administered to pigs, both the intradermally and intramuscularly vaccinated groups were protected completely against a challenge of the homologous FMDV, but the intramuscularly vaccinated group showed an overall higher level of neutralizing antibodies. Importantly, the formation of granuloma in muscle could be excluded in the intradermally vaccinated group. Of the oil-based adjuvants selected in this study, ISA 207 was effective in eliciting immunogenicity in intradermal vaccination. In conclusion, a new vaccine formula can be chosen for the delivery of intradermal route to exclude the possibility of local reactions in the muscle and generate protective immunity against an FMDV challenge.
Medical Versus Implanted Device Therapy for Patients With Heart Failure With Reduced Ejection Fraction.

Over the past several decades, numerous advances in pharmacological and implantable cardiac device therapy have led to improvement in quality of life and mortality in patients with heart failure (HF). β-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists, and, more recently, angiotensin receptor neprilysin inhibitors (ARNIs) represent medical therapies, which have each been clearly demonstrated to improve mortality in patients with heart failure and reduced ejection fraction (HFrEF). Implantable cardiac rhythm device therapies demonstrated to improve outcomes in these patients include implantable cardioverter defibrillators (ICDs) and cardiac resynchronization therapy (CRT). Each of these therapies has been reproducibly shown to improve mortality in patients with HFrEF when used either individually or in combination with each other. However, the relative benefit on mortality reduction with pharmacological versus device therapy in these patients has been difficult to ascertain. In the current issue of Circulation: Arrhythmia and Electrophysiology, Tseng et al1 report interesting novel findings from a comprehensive systematic review and network meta-analysis, which aimed to examine the effect of pharmacological and device therapies on mortality in patients with HFrEF. The authors screened through all relevant randomized controlled trials since 1980 and identified 68 qualifying studies, which were analyzed in the network meta-analysis (45 medication-related and 23 device-related). They examined the relationship between HFrEF and mortality with a causal directed acyclic graph and then used Bayesian analyses to combine information from multiple studies over time to compare efficacy of medical and device therapy. Using these techniques, they were able to create rankograms to depict which therapies were most likely to reduce all-cause mortality. Based on the results of their analyses, the authors reached the following conclusions: 1. Pharmacological therapies, with or without the addition of ICD and CRT therapy, are associated with significant reduction in all-cause mortality. 2. The best combinations of pharmacological and device therapy include (1) ICD+angiotensin receptor blockers+β-blockers (plus or minus mineralocorticoid receptor antagonist) or ARNI+β-blockers+mineralocorticoid receptor antagonist. 3. Outcomes with ARNI+β-blockers+mineralocorticoid receptor antagonist appear to be not significantly different compared with ICD+OMT. The first conclusion of this study is apparent: numerous studies have shown time and time again the benefit of pharmacological therapies to improve outcomes in patients with HFrEF. Medications can attenuate mortality by modifying the negaEDITORIAL
Styrylquinoline - a versatile scaffold in medicinal chemistry.

BACKGROUND Styrylquinolines are characteristic fully aromatic compounds with flat, rather lipophilic structures. The first reports on their synthesis and biological activity were published roughly a century ago. However, their low selectivity, unfavorable toxicity and problems with their mechanism of action significantly hampered their development. As a result, they have been abandoned for most of the time since they were discovered. OBJECTIVE Their renaissance was observed by the antiretroviral activity of several styrylquinoline derivatives that have been reported to be HIV integrase inhibitors. Subsequently, other activities such as their antifungal and anticancer abilities have also been revisited. METHODS In the present review, the spectrum of the activity of styrylquinolines and their use in drug design is presented and analyzed. RESULTS New properties and applications that were reported recently have re-established styrylquinolines within medicinal and material chemistry. The considerable increase in the number of published papers regarding to their activity spectrum will ensure further discoveries in the field. Conclusions Styrylquinolines have earned a much stronger position in medicinal chemistry due to the discovery of their new activities, profound mechanisms of action and as drug candidates in clinical trials.
OVARIAN GRANULOSA CELL TUMORS IN CHILDHOOD

Granulosa cell tumors (GCT) of the ovary are prepubertal in 5% of the patients. In girls less than 20 years old, 80% of GCTs differ from those among adults. These juvenile granulosa cell tumors (JGCTs) are usually benign. GCTs belong to ovarian sex cord-stromal tumors, the more common ovarian tumors being epidermal and germinal. The etiology of GCT remains unknown. Most young children with GCT present with precocious pseudopuberty. Among adolescents GCT often causes menstrual irregularities, virilization, abdominal swelling, and pain. When JGCT is limited to the ovaries the outcome is excellent with only salpingo-oophorectomy. However, more widely spread tumors are difficult to treat and cause mortality. Cisplatin-containing chemotherapy can induce remissions in adult GCTs. Estrogens and peptide hormones, i.e., inhibin, are useful in the follow-up of the patients. The authors describe 3 children with GCT and review current data on this rare tumor from molecular biology to clinical aspects.
Bigram Part-of-Speech Tagger for Myanmar Language

A variety of Natural Language Processing (NLP) tasks, such as machine translation, benefit from knowledge of the words syntactic categories or Part-of-Speech (POS). Since there is no state-of-the-art POS tagger for Myanmar language and POS tagging is a necessary process for Myanmar to English machine translation system, the development of a Bigram POS tagger is described in this paper. This tagger uses the customized POS tagset which is divided into two groups: basic and finer. Our Bigram tagger has two phases for disambiguating the basic POS tags: training with Hidden Markov Models (HMM) using Baum-Welch algorithm and decoding with Viterbi algorithm. Before disambiguation, word boundaries must be identified because words are not separated by spaces and there is no standard break among words in Myanmar Language. Therefore, the process for identifying each word has to be done in advance. After disambiguation, to produce the better output, normalization rules are used in order to form tagged words with the finer POS tags. This paper proposes an approach that will segment the input sentence to build meaningful words and tag these words with appropriate POS tags. By experiments, this approach has the best performance for known words with a few ambiguous tags. Experimental results show that our approach achieves high accuracy (over 90%) for different testing input.
The applicability of multiparameter flow cytometry for the detection of minimal residual disease using different‐from‐normal panels to predict relapse in patients with acute myeloid leukemia after allogeneic transplantation

The MRD status detected using multiparameter flow cytometry (MFC) before allogeneic hematopoietic stem cell transplantation (allo‐HSCT) has crucial prognostic value for patients with acute myeloid leukemia (AML) in morphologic complete remission (CR). We designed a novel panel of antibodies to identify aberrant differentiation/maturation profiles of residual leukemia cells in patients who were not diagnosed at our institution, relapsed with an antigenic shift, or lack leukemia‐associated immunophenotypes.
Analysis of the microRNA Expression Profile of Bovine Monocyte-derived Macrophages Infected with Mycobacterium avium subsp. Paratuberculosis Reveals that miR-150 Suppresses Cell Apoptosis by Targeting PDCD4

M. avium subsp. paratuberculosis (MAP) is the causative pathogen of Johne’s disease, a chronic granulomatous enteritis that principally affects ruminants and can survive, proliferate and disseminate in macrophages. MicroRNAs (miRNAs) are important regulators of gene expression and can impact the processes of cells. To investigate the role of miRNAs in monocyte-derived macrophages (MDMs) during MAP infection, we used high-throughput sequencing technology to analyze small RNA libraries of MAP-infected and control MDMs. The results showed that a total of 21 miRNAs were differentially expressed in MDMs after MAP infection, and 8864 target genes were predicted. A functional analysis showed that the target genes were mainly involved in the MAPK signaling pathway, Toll-like receptor signaling pathway, NF-kappa B signaling pathway and apoptosis. In addition, using a dual-luciferase reporter assay, flow cytometry, and a small interfering (si)RNA knockdown assay, the role of miR-150 in regulating macrophage apoptosis by targeting the programmed cell death protein-4 (PDCD4) was demonstrated. These results provide an experimental basis to reveal the regulatory mechanism of MAP infection and suggest the potential of miRNAs as biomarkers for the diagnosis of Johne’s disease in bovines.
Pathogenicity of clade 2.3.4.4 H5N6 highly pathogenic avian influenza virus in three chicken breeds from South Korea in 2016/2017

In 2016, novel H5N6 highly pathogenic avian influenza virus emerged in Korea. During the outbreak, the virus caused the largest culling, especially in brown chicken lines. We determined the pathogenicity and transmissibility of the virus in 2 white chicken lines of the specific pathogen-free chickens, broilers and brown chicken line of Korean native chicken (KNC). A KNC had a longer virus shedding period and longer mean death time than others. Our study showed that this characteristic in the KNC might have contributed to a farm-to-farm transmission of the brown chicken farms.
Depression and Physical Activity Affect Diet Quality of Foreign-born Latina Women Living on the U.S.-Mexico Border

There is increasing evidence that depression may affect diet. However, little is known about the association between depression and diet quality among foreign-born Latinas. We hypothesized that depressive symptoms would be associated with poorer diet quality in foreign-born Latinas. Furthermore, we believed that physical activity (PA) would have a protective effect on diet quality for individuals experiencing depressive symptoms. Our study evaluated the diet (Healthy Eating Index) and PA (Actigraph GT3X activity monitors) of 534 foreign-born Latinas with and without depressive symptoms (Center for Epidemiological Studies Depression Scale). A series of logistic regression models were estimated to examine our hypotheses. As predicted, Latinas who were depressed had significantly lower odds of having a high-quality diet than non-depressed Latinas. Unexpectedly, among Latinas who met PA guidelines, depressed Latinas had a significantly lower probability of having higher-quality diets than their non-depressed counterparts. Our findings support current research stating that depressive symptoms are associated with lower Healthy Eating Index scores. More research is necessary to elucidate the relationship between PA and dietary quality of depressed Latinas. Innovative approaches to address mental health and the stressors that can compound its severity are needed to improve diet quality among foreign-born Latina women.
Numerical Study on Effective Conditions for the Induction of Apoptotic Temperatures for Various Tumor Aspect Ratios Using a Single Continuous-Wave Laser in Photothermal Therapy Using Gold Nanorods

Photothermal therapy can serve as an alternative to classic surgery in the treatment of patients with cancer. However, using photothermal therapy can result in local overheating and damage to normal tissues. Therefore, it is important to determine effective heating conditions based on heat transfer. In this study, we analyzed laser–tissue interactions in gold nanoparticle (GNP)-enhanced photothermal therapy based on the theory of heat transfer. The thermal behavior inside tissues during photothermal therapy was analyzed using numerical analysis. The apoptosis ratio was defined by deriving the area having a temperature distribution between 43 °C and 50 °C, which is required for inducing apoptosis. Thermal damage, caused by local heating, was defined using the thermal hazard value. Using this approach, we confirmed that apoptosis can be predicted with respect to tumor size (aspect ratio) and heating conditions (laser intensity and radius) in photothermal therapy with a continuous-wave laser. Finally, we determined the effective apoptosis ratio and thermal hazard value of normal tissue according to tumor size and heating conditions, thereby establishing conditions for inducing maximal levels of cell apoptosis with minimal damage to normal tissue. The optimization conditions proposed in this study can be a gentle and effective treatment option for photothermal therapy.
Genomic Profiling of Tumor Necrosis Factor Alpha (TNF-α) Receptor and Interleukin-1 Receptor Knockout Mice Reveals a Link between TNF-α Signaling and Increased Severity of 1918 Pandemic Influenza Virus Infection

ABSTRACT The influenza pandemic of 1918 to 1919 was one of the worst global pandemics in recent history. The highly pathogenic nature of the 1918 virus is thought to be mediated in part by a dysregulation of the host response, including an exacerbated proinflammatory cytokine response. In the present study, we compared the host transcriptional response to infection with the reconstructed 1918 virus in wild-type, tumor necrosis factor (TNF) receptor-1 knockout (TNFRKO), and interleukin-1 (IL-1) receptor-1 knockout (IL1RKO) mice as a means of further understanding the role of proinflammatory cytokine signaling during the acute response to infection. Despite reported redundancy in the functions of IL-1β and TNF-α, we observed that reducing the signaling capacity of each of these molecules by genetic disruption of their key receptor genes had very different effects on the host response to infection. In TNFRKO mice, we found delayed or decreased expression of genes associated with antiviral and innate immune signaling, complement, coagulation, and negative acute-phase response. In contrast, in IL1RKO mice numerous genes were differentially expressed at 1 day postinoculation, including an increase in the expression of genes that contribute to dendritic and natural killer cell processes and cellular movement, and gene expression profiles remained relatively constant at later time points. We also observed a compensatory increase in TNF-α expression in virus-infected IL1RKO mice. Our data suggest that signaling through the IL-1 receptor is protective, whereas signaling through the TNF-α receptor increases the severity of 1918 virus infection. These findings suggest that manipulation of these pathways may have therapeutic benefit.