Miracle-dz/UniFAR-FTUs huggingface dataset:
Rapid Analysis of Circadian Phenotypes in Arabidopsis Protoplasts Transfected with a Luminescent Clock Reporter

The plant circadian clock allows the anticipation of daily changes to the environment. This anticipation aids the responses to temporally predictable biotic and abiotic stress. Conversely, disruption of circadian timekeeping severely compromises plant health and reduces agricultural crop yields. It is therefore imperative that we understand the intricate regulation of circadian rhythms in plants, including the factors that affect motion of the transcriptional clockwork itself. Testing circadian defects in the model plant Arabidopsis thaliana (Arabidopsis) traditionally involves crossing specific mutant lines to a line rhythmically expressing firefly luciferase from a circadian clock gene promoter. This approach is laborious, time-consuming, and could be fruitless if a mutant has no circadian phenotype. The methodology presented here allows a rapid initial assessment of circadian phenotypes. Protoplasts derived from mutant and wild-type Arabidopsis are isolated, transfected with a rhythmically expressed luminescent reporter, and imaged under constant light conditions for 5 days. Luminescent traces will directly reveal whether the free-running period of mutant plants is different from wild-type plants. The advantage of the method is that any Arabidopsis line can efficiently be screened, without the need for generating a stably transgenic luminescent clock marker line in that mutant background.
The Serum Analysis of Dampness Syndrome in Patients with Coronary Heart Disease and Chronic Renal Failure Based on the Theory of “Same Syndromes in Different Diseases”

Aim To analyze the serum metabolites in patients with coronary heart disease (CHD) showing dampness syndrome and patients with chronic renal failure (CRF) showing dampness syndrome and to seek the substance that serves as the underlying basis of dampness syndrome in “same syndromes in different diseases. ” Methods. Metabolic spectrum by GC-MS was performed using serum samples from 29 patients with CHD showing dampness syndrome and 32 patients with CRF showing dampness syndrome. The principal component analysis and statistical analysis of partial least squares were performed to detect the metabolites with different levels of expression in patients with CHD and CRF. Furthermore, by comparing the VIP value and data mining in METLIN and HMDB, we identified the common metabolites in both patient groups. Results (1) Ten differential metabolites were found in patients with CHD showing dampness syndrome when compared to healthy subjects. Meanwhile, nine differential metabolites were found in patients with CRF showing dampness syndrome when compared to healthy subjects. (2) There were 9 differential metabolites identified when the serum metabolites of the CHD patients with dampness syndrome were compared to those of CRF patients with dampness syndrome. There were 4 common metabolites found in the serums of both patient groups.
Clinical Features of Celiac Disease: A Prospective Birth Cohort

OBJECTIVES: To investigate clinical features of celiac disease (CD) and their association with risk factors for CD in a genetic risk birth cohort. METHODS: Children from 6 clinical centers in 4 countries positive for HLA-DR3-DQ2 or DR4-DQ8 were annually screened for tissue transglutaminase antibodies (tTGA) and assessed for symptoms by questionnaires. Associations of symptoms with anthropometrics, known risk factors for CD, tTGA levels, and mucosal lesions in those biopsied were examined. RESULTS: Of 6706 screened children, 914 developed persistent positive tTGA, 406 underwent biopsies, and 340 had CD. Compared with age-matched tTGA-negative children, those with persistent tTGA were more likely to have symptoms at 2 (34% vs 19%, P < .001) and 3 years of age (28% vs 19%, P = .009) but not at 4 years (27% vs 21%, NS). Z-scores for height, weight, and BMI did not differ between groups. In children with persistent tTGA, having ≥1 symptom was associated with family history of CD (odds ratio = 2.59, 95% confidence interval, 1.21–5.57) but not with age, gender, or HLA-DR3-DQ2 homozygosity. At seroconversion, tTGA levels were higher in symptomatic than asymptomatic children (P < .001), in those from CD families (P < .001), and in US participants (P < .001) but not associated with age, gender, or HLA genotype. tTGA levels correlated with severity of mucosal lesions both in symptomatic (r = 0.53, P < .001) and asymptomatic children (r = 0.22, P = .01). CONCLUSIONS: A majority of children detected with persistent tTGA in screenings are asymptomatic and have normal growth by age 4 years. tTGA levels correlate more strongly with severity of mucosal lesions in symptomatic as compared with asymptomatic children.
Scharioth Macula Lens: A new intraocular implant for low-vision patients with stabilized maculopathy- first experience.

AIMS To present the initial results of Scharioth Macula Lens (SML) implantation. The SML is a new add-on intraocular lens designed to increase uncorrected near visual acuity (UCVA) in patients with stabilized maculopathy. METHODS Eight patients were included in the study. All met the indication criteria before SML implantation. An SML was implanted in the better seeing eye. Near and distance visual acuity were tested. Possible complications and patient complaints were recorded and patients were asked about their quality of vision after SML implantation. The examination was carried out on day 1, 1 week, 1, 3 and 6 months after surgery. RESULTS Six-month-results are presented. Apart from one, all patients with the SML had good near visual acuity at a recommended reading distance of 15 cm. Preoperatively, the mean (min-max) near UCVA was J13 (J8-J16), mean distance BCVA was 0.27. Postoperatively, the best results were after 1 month - near UCVA was J2.5 (J1-J7), distance BCVA was 0.26. Three months after surgery, this decreased to J4.5 (J1-J8); distance VA remained 0.25. Six months postoperatively - near vision was J4 (J1-J8) and distance VA was unchanged. Patients reported problems with reading speed and reading distance. Daily exercise improved their reading ability. One patient converted to wet AMD 3 months post-implantation. CONCLUSION The SML is a new hope for low-vision patients. It acts as a magnifier in the eye. It is a suitable method for increasing near visual acuity in patients with inactive maculopathy.
Linkage and retention in HCV care for HIV‐infected populations: early data from the DAA era

There is currently no published data on the effectiveness of DAA treatment for elimination of HCV infection in HIV‐infected populations at a population level. However, a number of relevant studies and initiatives are emerging. This research aims to report cascade of care data for emerging HCV elimination initiatives and studies that are currently being evaluated in HIV/HCV co‐infected populations in the context of implementation science theory.
The Value of Protocol Biopsies to Identify Patients With De Novo Donor‐Specific Antibody at High Risk for Allograft Loss

De novo donor‐specific antibody (dnDSA) is associated with antibody‐mediated rejection (AMR) and allograft loss, yet the allograft histology associated with dnDSA remains unclear. The aim of this study was to examine the allograft histology associated with dnDSA in patients with serial surveillance biopsies. We retrospectively studied adult conventional solitary kidney transplant recipients from October 2007 to May 2014. The definition of dnDSA was new donor‐specific antibody (DSA) with mean fluorescence intensity (MFI) >1000. The incidence of dnDSA was 7.0% (54 of 771) over mean follow‐up of 4.2 ± 1.9 years. Patients with dnDSA had reduced death‐censored allograft survival (87.0% vs. 97.0% no dnDSA, p < 0.01). Moreover, 94% of patients received a biopsy after dnDSA (mean of three biopsies per patient). AMR was present in 25.0% and 52.9% of patients at dnDSA detection and at 1 year, respectively. Patients with both class I and II dnDSA had the highest rate of allograft loss. The higher the sum MFI at dnDSA detection, the higher the incidence of AMR. In conclusion, patients with dnDSA without AMR at time of detection may benefit from a follow‐up biopsy within 1 year because AMR can be missed initially. In addition, the dnDSA class and sum MFI at baseline appear to be prognostic. The higher the sum MFI of dnDSA at baseline, the higher the incidence of AMR.
Robust Physical-World Attacks on Deep Learning Models

Recent studies show that the state-of-the-art deep neural networks (DNNs) are vulnerable to adversarial examples, resulting from small-magnitude perturbations added to the input. Given that that emerging physical systems are using DNNs in safety-critical situations, adversarial examples could mislead these systems and cause dangerous situations.Therefore, understanding adversarial examples in the physical world is an important step towards developing resilient learning algorithms. We propose a general attack algorithm,Robust Physical Perturbations (RP2), to generate robust visual adversarial perturbations under different physical conditions. Using the real-world case of road sign classification, we show that adversarial examples generated using RP2 achieve high targeted misclassification rates against standard-architecture road sign classifiers in the physical world under various environmental conditions, including viewpoints. Due to the current lack of a standardized testing method, we propose a two-stage evaluation methodology for robust physical adversarial examples consisting of lab and field tests. Using this methodology, we evaluate the efficacy of physical adversarial manipulations on real objects. Witha perturbation in the form of only black and white stickers,we attack a real stop sign, causing targeted misclassification in 100% of the images obtained in lab settings, and in 84.8%of the captured video frames obtained on a moving vehicle(field test) for the target classifier.
Development of Antimicrobial Packaging Film Made from Poly(Lactic Acid) Incorporating Titanium Dioxide and Silver Nanoparticles

Polylactide (PLA)/nano-TiO2 and PLA/nano-TiO2/nano-Ag blends films were prepared by a solvent volatilization method. Compared to pure PLA film, the nano-blend films have low water vapor permeability (WVP) and a poor transparency. With the increase of the NPs in the PLA, the tensile strength (TS) and elastic modulus (EM) decreased, while the elongation at break (ε) increased. SEM analysis indicated a rougher cross-section of the nano-blend films. According to the FTIR analysis, no new chemical bonds were formed in the nano-blend films. By using DSC to examine the crystallization and melting behavior, the result shows that the NPs have no effect on the glass transition (Tg) and melting temperature (Tm), but they caused an increase on the cold crystallization (Tc) and crystallinity (Xc). TGA results show that the addition of nanoparticles significantly improved the thermal stability. The PLA nano-blend films show a good antimicrobial activity against. E. coli and Listeria monocytogenes. Most important, we carried out migration tests, and verified that the release of NPs from the nano-blend films was within the standard limits.
Spore Heat Activation Requirements and Germination Responses Correlate with Sequences of Germinant Receptors and with the Presence of a Specific spoVA2mob Operon in Foodborne Strains of Bacillus subtilis

ABSTRACT Spore heat resistance, germination, and outgrowth are problematic bacterial properties compromising food safety and quality. Large interstrain variation in these properties makes prediction and control of spore behavior challenging. High-level heat resistance and slow germination of spores of some natural Bacillus subtilis isolates, encountered in foods, have been attributed to the occurrence of the spoVA2mob operon carried on the Tn1546 transposon. In this study, we further investigate the correlation between the presence of this operon in high-level-heat-resistant spores and their germination efficiencies before and after exposure to various sublethal heat treatments (heat activation, or HA), which are known to significantly improve spore responses to nutrient germinants. We show that high-level-heat-resistant spores harboring spoVA2mob required higher HA temperatures for efficient germination than spores lacking spoVA2mob. The optimal spore HA requirements additionally depended on the nutrients used to trigger germination, l-alanine (l-Ala), or a mixture of l-asparagine, d-glucose, d-fructose, and K+ (AGFK). The distinct HA requirements of these two spore germination pathways are likely related to differences in properties of specific germinant receptors. Moreover, spores that germinated inefficiently in AGFK contained specific changes in sequences of the GerB and GerK germinant receptors, which are involved in this germination response. In contrast, no relation was found between transcription levels of main germination genes and spore germination phenotypes. The findings presented in this study have great implications for practices in the food industry, where heat treatments are commonly used to inactivate pathogenic and spoilage microbes, including bacterial spore formers. IMPORTANCE This study describes a strong variation in spore germination capacities and requirements for a heat activation treatment, i.e., an exposure to sublethal heat that increases spore responsiveness to nutrient germination triggers, among 17 strains of B. subtilis, including 9 isolates from spoiled food products. Spores of industrial foodborne isolates exhibited, on average, less efficient and slower germination responses and required more severe heat activation than spores from other sources. High heat activation requirements and inefficient, slow germination correlated with elevated resistance of spores to heat and with specific genetic features, indicating a common genetic basis of these three phenotypic traits. Clearly, interstrain variation and numerous factors that shape spore germination behavior challenge standardization of methods to recover highly heat-resistant spores from the environment and have an impact on the efficacy of preservation techniques used by the food industry to control spores.
Blood Draw Barriers for Treatment with Clozapine and Development of a Point-of-Care Monitoring Device.

BACKGROUND While clozapine (CLZ) is the most effective antipsychotic drug for schizophrenia treatment, it remains underused. In order to understand the barriers of frequent blood draws for white blood cell counts (WBCs) and clozapine levels, we developed a psychiatrist survey and began an integrative approach of designing a point-of-care device that could eventually have real-time monitoring with immediate results. METHODS We ascertained barriers related to CLZ management and the acceptance of possible solutions by sending an anonymous survey to physicians in psychiatric practice (n=860). In parallel, we tested CLZ sensing using a prototype point-of-care monitoring device. RESULTS 255 responses were included in the survey results. The two barriers receiving mean scores with the highest agreement as being a significant barrier were patient nonadherence to blood work and blood work's burden on the patient (out of 28). Among nine solutions, the ability to obtain lab results in the physician's office or pharmacy was top ranked (mean±sd Likert scale [4.0±1.0]). Physicians responded that a point-of-care device to measure blood levels and WBCs would improve care and increase CLZ use. Residents ranked point-of-care devices higher than older physicians (4.07±0.87 vs. 3.47±1.08, p<0.0001). Also, the prototype device was able to detect CLZ reliably in 1.6, 8.2, and 16.3 μg/mL buffered solutions. DISCUSSION Survey results demonstrate physicians' desire for point-of-care monitoring technology, particularly among younger prescribers. Prototype sensor results identify that CLZ can be detected and integrated for future device development. Future development will also include integration of WBCs for a complete detection device.
Rotavirus shedding following administration of RV3-BB human neonatal rotavirus vaccine

ABSTRACT The RV3-BB human neonatal rotavirus vaccine aims to provide protection from severe rotavirus disease from birth. A phase IIa safety and immunogenicity trial was undertaken in Dunedin, New Zealand between January 2012 and April 2014. Healthy, full-term (≥ 36 weeks gestation) babies, who were 0–5 d old were randomly assigned (1:1:1) to receive 3 doses of oral RV3-BB vaccine with the first dose given at 0–5 d after birth (neonatal schedule), or the first dose given at about 8 weeks after birth (infant schedule), or to receive placebo (placebo schedule). Vaccine take (serum immune response or stool shedding of vaccine virus after any dose) was detected after 3 doses of RV3-BB vaccine in >90% of participants when the first dose was administered in the neonatal and infant schedules. The aim of the current study was to characterize RV3-BB shedding and virus replication following administration of RV3-BB in a neonatal and infant vaccination schedule. Shedding was defined as detection of rotavirus by VP6 reverse transcription polymerase chain reaction (RT-PCR) in stool on days 3–7 after administration of RV3-BB. Shedding of rotavirus was highest following vaccination at 8 weeks of age in both neonatal and infant schedules (19/30 and 17/27, respectively). Rotavirus was detected in stool on days 3–7, after at least one dose of RV3-BB, in 70% (21/30) of neonate, 78% (21/27) of infant and 3% (1/32) placebo participants. In participants who shed RV3-BB, rotavirus was detectable in stool on day 1 following RV3-BB administration and remained positive until day 4–5 after administration. The distinct pattern of RV3-BB stool viral load demonstrated using a NSP3 quantitative qRT-PCR in participants who shed RV3-BB, suggests that detection of RV3-BB at day 3–7 was the result of replication rather than passage through the gastrointestinal tract.
Inflammatory biomarkers and intellectual disability in patients with Down syndrome

BACKGROUND Intellectual disability (ID) is part of the Down syndrome (DS) phenotypic spectrum, but the exact molecular pathophysiology of ID in individuals with DS is not yet fully understood, with many research hypotheses still unproven. Basing on previous studies (which suggested a possible role of altered inflammatory response in DS-related ID), we assessed the serum levels of a number of inflammatory biomarkers [serum amyloid A (SAA), C-reactive protein (C-RP), high mobility group box-1 (HMGB1)] in a cohort of individuals with DS and healthy controls. METHODS In total, 24 children diagnosed with DS and 12 healthy controls were enrolled, and all underwent detailed cognitive assessment. Also, serum SAA, C-RP and HMGB1 levels were measured in all recruited subjects and correlated to the severity of ID in the DS group. RESULTS Serum SAA, C-RP and HMGB1 values were found to be significantly higher in the DS group compared with the healthy subjects (P = 0.001). In addition, serum HMGB1 levels positively correlated with C-RP and SAA in the DS group but not in the healthy controls. Only serum C-RP levels resulted inversely correlated (P < 0.01) with intelligence quotient (IQ); conversely, significant statistical correlations between serum SAA levels and IQ (as well as between HMGB1 and IQ) have been not found (P > 0.05). CONCLUSIONS The levels of the determined markers were higher in DS individuals compared with (cognitively) healthy subjects, and CRP showed a negative correlation with IQ in children with DS.
Insulin-like growth factor-1 restores dexamethasone-induced heart growth arrest in rats: the role of the ubiquitin pathway

OBJECTIVE: In skeletal muscle, glucocorticoids induce catabolism and proteolysis which is accomplished via the ubiquitin (Ub) proteolytic pathway. Cardiac muscle is a striated muscle which, compared to skeletal muscle, more abundantly expresses components of the Ub pathway, thus suggesting an important role for this pathway in heart physiology. The aim of our study was to explore the role of the Ub pathway in heart muscle physiology. DESIGN: We treated rats for three days with a pharmacologic dose of dexamethasone (DEXA) 0.5mg/100g body weight (BW). An attempt was also made to counteract the DEXA effect by co-treatment with insulinlike growth factor-1 (IGF-1; 0.35mg/100g BW). RESULTS: DEXA treatment caused a 7.8% decrease in heart weight compared to control (p<0.05) and also increased heart tissue levels of the ubiquitin-conjugating enzyme E2 and the 20S proteasome protein. Myofibrillar proteins degraded by the ubiquitin pathway (α-actin, myoglobin, and troponin 1) were all decreased by DEXA, while ubiquitinated forms of α-actin were increased. Co-treatment with IGF-1 completely prevented DEXA-induced decrease in heart weight, an effect which was accompanied by decreased heart tissue levels of several ubiquitinated proteins including α-actin, the 20S proteasome protein, E2-14kDa mRNA, and C-3 proteasome subunit mRNA, while the levels of non-ubiquinated α-actin, myoglobin, and troponin 1 were all partially restored. CONCLUSION: These results demonstrate that DEXA activates the ubiquitin proteolytic pathway in the heart and that IGF-1 efficiently counteracts this effect. Our findings reveal a possible mechanism for the anti-proteolytic actions of IGF-1 and its cardioprotective role involving the Ub pathway.
Phonological Working Memory for Words and Nonwords in Cerebral Cortex.

Purpose The primary purpose of this study was to identify the brain bases of phonological working memory (the short-term maintenance of speech sounds) using behavioral tasks analogous to clinically sensitive assessments of nonword repetition. The secondary purpose of the study was to identify how individual differences in brain activation were related to participants' nonword repetition abilities. Method We used functional magnetic resonance imaging to measure neurophysiological response during a nonword discrimination task derived from standard clinical assessments of phonological working memory. Healthy adult control participants (N = 16) discriminated pairs of real words or nonwords under varying phonological working memory load, which we manipulated by parametrically varying the number of syllables in target (non)words. Participants' cognitive and phonological abilities were also measured using standardized assessments. Results Neurophysiological responses in bilateral superior temporal gyrus, inferior frontal gyrus, and supplementary motor area increased with greater phonological working memory load. Activation in left superior temporal gyrus during nonword discrimination correlated with participants' performance on standard clinical nonword repetition tests. Conclusion These results suggest that phonological working memory is related to the function of cortical structures that canonically underlie speech perception and production.