Miracle-dz/UniFAR-FTUs huggingface dataset:
Three Emerging Coronaviruses in Two Decades

In the past two decades, the world has seen three coronaviruses emerge and cause outbreaks that have caused considerable global health consternation Coronaviruses are enveloped, nonsegmented, single-stranded, positive-sense RNA viruses that have a characteristic appearance on electron microscopy negative staining Image 1 As a matter of fact, the characteristic electron microscopy appearance was the clue to amplify and sequence nucleic acids from Dr Urbani’s (one of the health care providers who died of severe acute respiratory syndrome [SARS] in 2003) respiratory specimen using a consensus coronavirus primer 1 The sequence of the virus was significantly different from other coronaviruses known to cause human disease at the time The virus was ultimately named SARS-CoV, as febrile patients had severe acute respiratory syndrome and could present with pneumonia and lower respiratory symptoms such as cough and dyspnea 2 The SARS-CoV outbreak started in Guangdong, China, and spread to many countries in Southeast Asia, North America, Europe, and South Africa Transmission was primarily person to person through droplets that occurred during coughing or sneezing, through personal contact (shaking hands), or by touching contaminated surfaces Of note, health professionals were particularly at risk of acquiring the disease, as transmission also occurred if isolation precautions were not followed and during certain procedures The last case of SARS-CoV occurred in September 2003, after having infected over 8,000 persons and causing 774 deaths with a case fatality rate calculated at 9 5%
A Comparative Study on the Self-Assembly of Peptide TGV-9 by In Situ Atomic Force Microscopy

Abstract Previous studies of amyloid diseases reported that the aggregating proteins share a similar conserved peptide sequence which can form the cross-β-sheet-containing nanostructures like nanofilaments. The template-assisted self-assembly (TASA) of peptides on inorganic substrates with different hydrophilicity could be an alternative approach to shed light on the fibrillization mechanism of proteins/peptides in vivo. To figure out the effect of interfaces on amyloid aggregation, we herein employed in situ atomic force microscopy (AFM) to investigate the self-assembling of a Parkinson disease-related core peptide sequence (TGV-9) on a hydrophobic liquid–solid interface via real-time observation of the dynamic fibrillization process. The results show that TGV-9 forms one-dimensional nanostructures on the surface of highly ordered pyrolytic graphite (HOPG) with three preferred growth orientations, which are consistent with the atomic lattice of HOPG, indicating an epitaxial growth or TASA. Conversely, the nanostructures formed in bulk solution can be free-standing nanofilaments, and the fibrillization mechanism is different from that on HOPG. These results could not only deepen the understanding of the protein/peptide aggregation mechanism but also benefit for the early diagnosis and clinic treatment of related diseases.
Effect of Pembrolizumab Plus Neoadjuvant Chemotherapy on Pathologic Complete Response in Women With Early-Stage Breast Cancer: An Analysis of the Ongoing Phase 2 Adaptively Randomized I-SPY2 Trial.

Importance Approximately 25% of patients with early-stage breast cancer who receive (neo)adjuvant chemotherapy experience a recurrence within 5 years. Improvements in therapy are greatly needed. Objective To determine if pembrolizumab plus neoadjuvant chemotherapy (NACT) in early-stage breast cancer is likely to be successful in a 300-patient, confirmatory randomized phase 3 neoadjuvant clinical trial. Design, Setting, and Participants The I-SPY2 study is an ongoing open-label, multicenter, adaptively randomized phase 2 platform trial for high-risk, stage II/III breast cancer, evaluating multiple investigational arms in parallel. Standard NACT serves as the common control arm; investigational agent(s) are added to this backbone. Patients with ERBB2 (formerly HER2)-negative breast cancer were eligible for randomization to pembrolizumab between November 2015 and November 2016. Interventions Participants were randomized to receive taxane- and anthracycline-based NACT with or without pembrolizumab, followed by definitive surgery. Main Outcomes and Measures The primary end point was pathologic complete response (pCR). Secondary end points were residual cancer burden (RCB) and 3-year event-free and distant recurrence-free survival. Investigational arms graduated when demonstrating an 85% predictive probability of success in a hypothetical confirmatory phase 3 trial. Results Of the 250 women included in the final analysis, 181 were randomized to the standard NACT control group (median [range] age, 47 [24.77] years). Sixty-nine women (median [range] age, 50 [27-71] years) were randomized to 4 cycles of pembrolizumab in combination with weekly paclitaxel followed by AC; 40 hormone receptor (HR)-positive and 29 triple-negative. Pembrolizumab graduated in all 3 biomarker signatures studied. Final estimated pCR rates, evaluated in March 2017, were 44% vs 17%, 30% vs 13%, and 60% vs 22% for pembrolizumab vs control in the ERBB2-negative, HR-positive/ERBB2-negative, and triple-negative cohorts, respectively. Pembrolizumab shifted the RCB distribution to a lower disease burden for each cohort evaluated. Adverse events included immune-related endocrinopathies, notably thyroid abnormalities (13.0%) and adrenal insufficiency (8.7%). Achieving a pCR appeared predictive of long-term outcome, where patients with pCR following pembrolizumab plus chemotherapy had high event-free survival rates (93% at 3 years with 2.8 years' median follow-up). Conclusions and Relevance When added to standard neoadjuvant chemotherapy, pembrolizumab more than doubled the estimated pCR rates for both HR-positive/ERBB2-negative and triple-negative breast cancer, indicating that checkpoint blockade in women with early-stage, high-risk, ERBB2-negative breast cancer is highly likely to succeed in a phase 3 trial. Pembrolizumab was the first of 10 agents to graduate in the HR-positive/ERBB2-negative signature. Trial Registration ClinicalTrials.gov Identifier: NCT01042379.
Electrocardiographic Changes in Liver Cirrhosis—Clues for Cirrhotic Cardiomyopathy

Background and Objectives: Cirrhotic cardiomyopathy is a chronic cardiac dysfunction associated with liver cirrhosis, in patients without previous heart disease, irrespective of the etiology of cirrhosis. Electrocardiography (ECG) is an important way to evaluate patients with cirrhosis and may reveal significant changes associated with liver disease. Our study aimed to evaluate ECG changes in patients with diagnosed liver cirrhosis and compare them to patients with chronic hepatitis. Materials and Methods: We evaluated laboratory findings and ECG tracings in 63 patients with cirrhosis and 54 patients with chronic hepatitis of viral etiology. The end points of the study were prolonged QT interval, QRS hypovoltage and T-peak-to-T-end decrease. We confirmed the diagnosis of cirrhotic cardiomyopathy using echocardiography data. Results: Advanced liver disease was associated with prolonged QT intervals. Also, QRS amplitude was lower in patients with decompensated cirrhosis than in patients with compensated liver disease. We found an accentuated deceleration of the T wave in patients with cirrhosis. These findings correlated to serum levels of albumin, cholesterol and ammonia. Conclusions: ECG changes in liver cirrhosis are frequently encountered and are important noninvasive markers for the presence of cirrhotic cardiomyopathy.
Let it bloom: cross‐talk between light and flowering signaling in Arabidopsis

The terrestrial environment is complex, with many parameters fluctuating on daily and seasonal basis. Plants, in particular, have developed complex sensory and signaling networks to extract and integrate information about their surroundings in order to maximize their fitness and mitigate some of the detrimental effects of their sessile lifestyles. Light and temperature each provide crucial insights on the surrounding environment and, in combination, allow plants to appropriately develop, grow and adapt. Cross‐talk between light and temperature signaling cascades allows plants to time key developmental decisions to ensure they are ‘in sync’ with their environment. In this review, we discuss the major players that regulate light and temperature signaling, and the cross‐talk between them, in reference to a crucial developmental decision faced by plants: to bloom or not to bloom?
Constitutive activity of a G protein‐coupled receptor, DRD1, contributes to human cerebral organoid formation

The intricate balance of neural stem cell (NSC) amplification and neurogenesis is central to nervous system development. Dopamine D1 receptor (DRD1) is a typical G protein‐coupled receptor (GPCR) mainly expressed in neurogenic area, with high constitutive activity. The receptor appears in the embryonic period before the formation of mature synaptic contacts, which indicates that dopamine receptor and its constitutive activity play crucial roles in the embryonic brain development. Here, we found that DRD1 was enriched in human NSCs. Inhibition of the receptor activity by its inverse agonists promoted human NSCs proliferation and impeded its differentiation. These results were also mimicked by genetic knockdown of DRD1, which also blocked the effects of inverse agonists, suggesting a receptor‐dependent manner. More interestingly, knock‐in A229T mutant with reduced DRD1 constitutive activity by CRISPR‐Cas9 genome editing technology resulted into increased endogenous human NSCs proliferation. These results were well reproduced in human cerebral organoids, and inhibition of the DRD1 constitutive activity by its inverse agonists induced the expansion and folding of human cerebral organoids. The anatomic analysis uncovered that decreasing the constitutive activity of DRD1 by its inverse agonists promoted the NSCs proliferation and maintenance that led to hindered cortical neurogenesis. Further mechanistic studies revealed that the PKC‐CBP pathway was involved in the regulation by DRD1. Thus, our findings indicate that the constitutive activity of DRD1 and possibly other GPCRs plays an important role in the development of human nervous system.
Maxillomandibular Advancement for the Treatment of Obstructive Sleep Apnea in Patients With Normal or Class I Malocclusion.

BACKGROUND Maxillomandibular advancement is an effective surgical option for obstructive sleep apnea (OSA) that achieves enlargement of the upper airway by physically expanding the facial skeleton. The authors sought to determine whether an advancement of 10 mm predicts surgical success and if any correlation existed between the magnitude of mandibular/maxillary advancement and improvement in polysomnography metrics using aggregated individual patient data from multiple studies. METHODS A search of the PubMed database was performed to identify relevant articles that included preoperative and postoperative polysomnography data and measurements of the advancement of both the maxillary and mandibular portions of the face in patients with normal or class I malocclusion. Each patient was stratified into "Success" or "Failure" groups based on criteria defining a "Success" as a 50% preoperative to post-operative decrease in AHI or RDI and a post-operative AHI or RDI <20. RESULTS A review of the PubMed database yielded 162 articles. Review of these resulted in 9 manuscripts and a total of 109 patients who met the inclusion criteria. There was no statistically significant difference in the amount of anterior advancement of either the mandible (P = 0.96) or the maxilla (P = 0.23) between the "Success" or "Failure" groups. CONCLUSIONS While there is a paucity of individual data available, the current data does not support an ideal amount of maxillary or mandibular advancement that is required to obtain a surgical success in the treatment of OSA. Until a multicenter, prospective, randomized trial is performed, surgical planning should be tailored to patient-specific anatomy to achieve the desired result.
Efficacy of Alveolar Ridge Preservation: A Randomized Controlled Trial

Alveolar ridge preservation (ARP) therapy is indicated to attenuate the physiologic resorptive events that occur as a consequence of tooth extraction with the purpose of facilitating tooth replacement therapy. This randomized controlled trial was primarily aimed at testing the efficacy of ARP as compared with unassisted socket healing. A secondary objective was to evaluate the effect that local phenotypic factors play in the volumetric reduction of the alveolar bone. A total of 53 subjects completed the study. Subjects were randomized into either the control group, which involved only tooth extraction (EXT n = 27), or the experimental group, which received ARP using a combination of socket grafting with a particulate bone allograft and socket sealing with a nonabsorbable membrane (dPTFE) following tooth extraction (ARP n = 26). A set of clinical, linear, volumetric, implant-related, and patient-reported outcomes were assessed during a 14-wk healing period. All linear bone assessments (horizontal, midbuccal, and midlingual reduction) revealed that ARP is superior to EXT. Likewise, volumetric bone resorption was significantly higher in the control group (mean ± SD: EXT = −15.83% ± 4.48%, ARP = −8.36% ± 3.81%, P < 0.0001). Linear regression analyses revealed that baseline buccal bone thickness is a strong predictor of alveolar bone resorption in both groups. Interestingly, no significant differences in terms of soft tissue contour change were observed between groups. Additional bone augmentation to facilitate implant placement in a prosthetically acceptable position was deemed necessary in 48.1% of the EXT sites and only 11.5% of the ARP sites (P < 0.004). Assessment of perceived postoperative discomfort at each follow-up visit revealed a progressive decrease over time, which was comparable between groups. Although some extent of alveolar ridge remodeling occurred in both groups, ARP therapy was superior to EXT as it was more efficacious in the maintenance of alveolar bone and reduced the estimated need for additional bone augmentation at the time of implant placement (ClinicalTrials.gov NCT01794806).
Linkages between changes in plant and mycorrhizal fungal community composition at high versus low elevation in alpine ecosystems.

Arbuscular mycorrhizal fungi (AMF) play an important role in maintaining plant diversity and productivity in grassland ecosystems. However, very few studies have investigated how AMF and plant communities co-vary between contrasting environments in natural ecosystems. Intensive sampling (50 soil samples) was conducted in natural open grasslands at both 3570 and 4556 m on Mount Segrila on the Southeast Tibetan Plateau. We used 454-pyrosequencing to investigate soil AMF communities and to explore relationships between AMF diversity and plant richness, productivity and community composition. AMF diversity was negatively correlated with plant richness at 3570 m but positively at 4556 m. Differences in AMF community composition between elevations were attributable to plant community composition, soil pH and available phosphorus concentration. The AMF community was more phylogenetically clustered at the higher elevation than the lower elevation. However, greater phylogenetic clustering (under dispersion) of AMF communities at the two elevations was positively correlated with above-ground biomass. Our results indicate that plant community composition and environmental filtering are the primary drivers structuring the AMF community. Phylogenetic relatedness may be important in explaining the function of AMF communities in alpine ecosystems.
Hospice Care: Hope and Meaning in Life Mediate Subjective Well-Being of Staff

Objectives: Subjective well-being has been associated with decreased work burnout and elevated work engagement. We investigated the impact of hope and meaning in life on subjective well-being among workers in a hospice care setting. Comparison was made to health-care workers in a rehabilitation unit. Methods: Thirty-five hospice care workers were surveyed and their responses compared with those of 36 rehabilitation workers. Survey instruments measuring hope, meaning in life, work engagement, and satisfaction with life were utilized. Results: Individuals working in a hospice care center have significantly higher levels of work engagement than their counterparts in rehabilitation. For both groups, hope was significantly related to subjective well-being. For hospice care but not rehabilitation workers, meaning in life was also related to subjective well-being. Multivariate analysis showed that hope and meaning in life were independent factors predicting subjective well-being in hospice care workers. Significance of Results: Hospice care workers are highly engaged in their work despite the challenging nature of their work. What characterizes these workers is a level of subjective well-being that is related to both meaning in life and hope. Maintaining a high level of subjective well-being may be an important factor in preventing burnout among those working in hospice care settings.
DIVERSITY AND MARKETING OF DRIED FISH PRODUCTS IN NEPAL

Various dried fish products are available in Nepalese markets. The information on diversity and marketing system of dried fish products in the country is scanty. Survey on dried fish was carried out in 19 districts to elucidate the species diversity, market channels and consumer’s preference of dried fish. Exotic species such as Harpodon nehereus, Penaeus spp. , Stolephorus spp. imported from several Asian countries shares approximately 70 percent of the dried fish market of the country. The dried fish products available in the market are in the form of sun-dried, smoked, spicy instant fish and fish pickle. Marketing system of dried fish varies for indigenous captured fish, cultured fish and imported fish. Price of dried fish varied greatly being high in rainy season associated with short supply and increased demand, and relatively low during winter months because of excess supply. Survey findings indicated that consumer’s preference on dried fish species is different with their different believes, traditional knowledge and eco-region. However, quality of dried fish available in market is a concern.
Assessing Students’ Mathematical Misconceptions through Concept Maps and Online Discussion Transcripts: Inner Product Spaces

Knowing students’ mathematical misconceptions can help educators trace the sources of the cause and help students learn conceptual and procedural knowledge in balance. This study aims to investigate students' misconceptions through students’ concept maps and online discussion transcripts. This case study takes the inner product spaces as the learning subjects. The types of misconceptions are investigated based on the source of errors. Based on the findings, the author identifies students’ learning difficulties and proposes certain learning activities to help students learn.
Electoral Cycles in Food Prices: Evidence from India

Do prices of essential food commodities vary with the timing of elections? Using weekly retail price data of 16 food items between 1993 and 2012 in 28 cities across India, we nd existence of a ‘political price cycle’ in onions and not in other commodities, conrming a commonly held (but hitherto empirically untested) view that onion prices are an electorally salient issue. ere is suggestive evidence that the opportunistic cycles are strongest when: (a) incumbent state governments are aligned with the center, (b) incumbent state governments win with large majorities, and (c) in periods when the market is unregulated. e ndings can be explained by the role of informal regulatory strategies such as collusion between incumbent governments and trading cartels, who exercise signicant inuence in the market supply of onions.
LaeA-Like Methyltransferases in Penicillium chrysogenum

The nine LaeA-like methyltransferases in Penicillium chrysogenum contain the same S-adenosyl-methionine (SAM) binding domain -with a nuclear localization signal at the N-terminus sequenceas the primary identified LaeA protein. While LaeA was identified as a positive global regulator, the LaeA-like methyltransferases, in particular PcLlm3 and PcLlm7, exhibit negative affect by silencing secondary metabolite pathways in industrial strain of P. chrysogenum. The high transcription of Pcllm7 and even higher Pcllm3 transcript level in the more industrially advanced strain indicated the possible role in regulation of Nonribosomal Peptide Synthetases (NRPSs) and Polyketide Synthases (PKSs). Deletion of Pcllm3 and Pcllm7 caused activation of the pks11 expression, whose transcript level was enhanced in the double mutant ∆Pcllm3∆Pcllm7. This study reveals the function of PcLlm3 and PcLlm7 as negative transcriptional regulators. 3 3.
Scientific Productivity and Academic Promotion: A Study on French and Italian Physicists

The paper examines the determinants of scientific productivity (number of articles and journals' impact factor) for a panel of about 3600 French and Italian academic physicists active in 2004-05. Endogeneity problems concerning promotion and productivity are addressed by specifying a generalized Tobit model, in which a selection probit equation accounts for the individual scientist's probability of promotion to her present rank, and a productivity regression estimates the effects of age, gender, cohort of entry, and collaboration characteristics, conditional on the scientist's rank. We find that the size and international nature of collaborative projects and co-authors' past productivity have very significant impacts on current productivity, while age and gender, and past productivity are also influential determinants of both productivity and probability of promotion. Furthermore we show that the stop-and-go policies of recruitment and promotion, typical of the Italian and French centralized academic systems of governance, can leave significant long-lasting cohort effects on research productivity.
An Empirical Evaluation on Robustness and Uncertainty of Regularization Methods

Despite apparent human-level performances of deep neural networks (DNN), they behave fundamentally differently from humans. They easily change predictions when small corruptions such as blur and noise are applied on the input (lack of robustness), and they often produce confident predictions on out-of-distribution samples (improper uncertainty measure). While a number of researches have aimed to address those issues, proposed solutions are typically expensive and complicated (e.g. Bayesian inference and adversarial training). Meanwhile, many simple and cheap regularization methods have been developed to enhance the generalization of classifiers. Such regularization methods have largely been overlooked as baselines for addressing the robustness and uncertainty issues, as they are not specifically designed for that. In this paper, we provide extensive empirical evaluations on the robustness and uncertainty estimates of image classifiers (CIFAR-100 and ImageNet) trained with state-of-the-art regularization methods. Furthermore, experimental results show that certain regularization methods can serve as strong baseline methods for robustness and uncertainty estimation of DNNs.