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Antiviral drugs do not currently exist for the treatment of enterovirus infections, which are often severe and potentially life-threatening. We conducted high-throughput molecular screening and identified a structurally diverse set of compounds that inhibit the replication of coxsackievirus B3, a commonly encountered enterovirus. These compounds did not interfere with the function of the viral internal ribosome entry site or with the activity of the viral proteases, but they did drastically reduce the synthesis of viral RNA and viral proteins in infected cells. Sequence analysis of compound-resistant mutants suggests that the viral 2C protein is targeted by most of these compounds. These compounds demonstrated antiviral activity against a panel of the most commonly encountered enteroviruses and thus represent potential leads for the development of broad-spectrum anti-enteroviral drugs.

The Belt and Road Initiative (BRI) is a massive, ambitious, long-term project initiated by the Chinese government, with participation from many other countries, to facilitate trade and improve logistics in an effort to promote global economic development. In this paper, we identified the supply chain and logistics innovations linked to the BRI. These innovations include new routes and modes for global trade, new supply chain design, reduction of cross-border logistics frictions, and entrepreneurial development. Examples of some of these innovations are emerging, while new ones are being developed. These innovations can enable businesses to improve their operational performances and create economic value. At the same time, to realize the full potentials of BRI, new work processes and technologies, incentive alignment, collaborations among businesses, and optimized planning are needed. This provides great opportunities for researchers to explore how to overcome barriers and achieve the full values of BRI.

Abstract Background This study aims to investigate the application value of three-dimensional arterial spin labeling (3DASL) in investigating cerebral blood flow dynamics in full-term neonates. Methods A total of 60 full-term neonates without known intracranial pathology were recruited for 3DASL examination. These neonates were divided into three groups: 1–3 day group, 4–7 day group, and 8–15 day group. On the cerebral blood flow (CBF) images, regions of interest (ROI) were selected from the frontal white matter, parietal white matter, basal ganglia, corona radiata, thalamus and brainstem, and the CBF values of each ROI were recorded. The CBF values of ROIs at bilaterally symmetric locations, the values of each ROI between males and females, and the values of each ROI among these three different age groups were compared. Results The difference in CBF values of the frontal white matter, parietal white matter, basal ganglia, corona radiata and thalamus at the bilateral symmetric positions were not statistically significant. There was no statistical difference in the CBF values of each brain region between the male and female groups. The CBF values at the basal ganglia region, corona radiata and parietal white matter were higher in the 8–15 day group, when compared to the 1–3 day and 4–7 day groups (P

Background The identification of V‐raf murine sarcoma viral oncogene homolog B1 (BRAF)V600E mutations has been recommended in patients with Langerhans cell histiocytosis (LCH) with difficult diagnosis and failure of first‐line treatment. The reported frequencies of BRAFV600E mutations vary in Chinese patients with LCH. Methods We conducted a retrospective analysis of LCH patients with a definitive pathological diagnosis who were hospitalized between 2013 and 2017. The BRAFV600E mutations were detected with the human BRAFV600E amplification refractory mutation system‐PCR (ARMS‐PCR) kit from the collected tissue samples. Results This study consisted of 46 male (68.7%) and 21 female (31.3%) patients, with a mean age of 29.1 years (range, 2–76 years). Most were adults (45/67.2%) with the multisysytem‐LCH (MS‐LCH) disease subtype (49/61.3%). The overall frequency of BRAFV600E mutations was 22.4% (15 of 67 patients), confirmed by PCR analysis. These mutations were not closely correlated with age (nonadults vs. adults = 5/22.7% vs. 10/22.2%, P = 0.54), gender (female vs. male = 9/19.6% vs. 6/28.6%, P = 0.61), LCH classification type (single system: MS‐risk organ+: MS‐risk organ− = 3/16.7%: 12:28.6%: 0, P = 0.19) or prognosis (cured: improved/stable: exacerbated: died = 4/44.4%: 19.2%: 20%: 0, P = 0.37). There were 33 patients (49.2%) with lung involvement, and 12 patients (36.3%) underwent lung biopsies; after screening, four patients were diagnosed with solitary pulmonary LCH, all of whom were negative for BRAFV600E mutations. Conclusion The BRAFV600E mutation rate in patients with LCH was lower than those reported in other studies. In addition, BRAFV600E mutations might not be correlated with age, gender, LCH classification type or prognosis for Chinese cases.

Abstract Purpose To evaluate and determine age‐related changes in rat brains by studying the diffusion kurtosis imaging results among different age groups of rats. Methods Sprague–Dawley (SD) rats underwent conventional magnetic resonance imaging (MRI) and diffusion Kurtosis Imaging (DKI). Two diffusion values of mean kurtosis (MK) and kurtosis (K⊥) were measured and analyzed based on laterality, brain regions and age groups. The MK and K⊥ data were plotted against different age groups. Results No laterality was found for the MK or K⊥ values in the cerebral cortex (CT), external capsule (EC), or caudate putamen (CPu) regions. In contrast, significant changes in these values were observed among different age groups. Changes of the MK and K⊥ values were significant in both hemispheres in the EC, the CT, and the CPu brain regions. The changes in the MK and K⊥ values showed a parabolic relationship with ages in all the brain regions. Conclusion No laterality in the MK and K⊥ values was observed for the EC, CT, or CPu regions of the rat brain. Significant changes in MK and K⊥ values were both observed among different age groups, thus suggesting diffusion kurtosis imaging as an efficient tool for studying brain aging in rats.

Background: The contemporary incidence of heart failure (HF) in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) remains unclear. This prospective cohort study was designed to study the incidence and predictors of new-onset HF in CAD patients after PCI (ChiCTR1900023033).Methods: From January 2014 to December 2018, 3,910 CAD patients without HF history undergoing PCI were prospectively enrolled. Demographics, medical history, cardiovascular risk factors, cardiac parameters, and medication data were collected at baseline. Multivariable adjusted competing-risk regression analysis was performed to examine the predictors of incident HF.Results: After a median follow-up of 63 months, 497 patients (12.7%) reached the primary endpoint of new-onset HF, of which 179, 110, and 208 patients (36.0, 22.1, and 41.9%) were diagnosed as having HF with reduced ejection fraction (EF) (HFrEF), HF with mid-range EF (HFmrEF), and HF with preserved EF (HFpEF), respectively. Higher B-type natriuretic peptide (BNP) or E/e′ level, lower estimated glomerular filtration rate (eGFR) level, and atrial fibrillation were the independent risk factors of new-onset HF. Gender (male) and angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker (ACEI/ARB) prescription were the negative predictors of new-onset HF. Moreover, it was indicated that long-term ACEI/ARB therapy, instead of beta-blocker use, was linked to lower risks of development of all three HF subtypes (HFrEF, HFmrEF and HFpEF).Conclusions: This prospective longitudinal cohort study shows that the predominant subtype of HF after PCI is HFpEF and ACEI/ARB therapy is accompanied with reduced risks of incident HF across three subtypes.

BackgroundOccurrence of portal vein tumor thrombus (PVTT) worsens the outcomes of hepatocellular carcinoma (HCC) and imparts high economic burden on society. Patients with high risks of having hypercoagulation are more likely to experience thrombosis. Herein, we examined how preoperative international normalized ratio (INR) was related to the incidence and extent of PVTT, and associated with survival outcomes in HCC patients following R0 liver resection (LR).MethodsPatients with HCC and PVTT were enrolled from six major hospitals in China. The overall survival (OS) and recurrence-free survival (RFS) rates of individuals with different INR levels were assessed with Cox regression analysis as well as Kaplan-Meier method.ResultsThis study included 2207 HCC patients, among whom 1005 patients had concurrent PVTT. HCC patients in the Low INR group had a significantly higher incidence of PVTT and more extensive PVTT than the Normal and High INR groups (P

Problem definition: We consider intertemporal pricing in the presence of reference effects and consumer heterogeneity. Our research question encompasses how to estimate heterogeneous consumer reference effects from data and how to efficiently compute the optimal pricing policy. Academic/practical relevance: Understanding reference effects is essential for designing pricing policies in modern retailing. Our work contributes to this area by incorporating consumer heterogeneity under arbitrary distributions. Methodology: We propose a mixed logit demand model that allows arbitrary joint distributions of valuations, responsiveness to prices, and responsiveness to reference prices among consumers. We use a nonparametric estimation method to learn consumer heterogeneity from transaction data. Further, we formulate the pricing optimization as an infinite horizon dynamic programming problem and solve it by applying a modified policy iteration algorithm. Results: Moreover, we investigate the structure of optimal pricing policies and prove the suboptimality of constant pricing policies even when all consumers are loss-averse according to the classical definition. Our numerical studies show that our estimation and optimization framework improves the expected revenue of retailers via accounting for heterogeneity. We validate our model using real data from JD.com, a large E-commerce retailer, and find empirical evidence of consumer heterogeneity. Managerial implications: In practice, ignoring consumer heterogeneity may lead to a significant loss of revenue. Furthermore, heterogeneous reference effect offers a strong motive for promotions and price fluctuations. History: This paper has been accepted as part of the 2020 MSOM Data Driven Research Challenge. Funding: This work was partially supported by the National Natural Science Foundation of China [Grant 71991462]. Supplemental Material: The e-companion is available at https://doi.org/10.1287/msom.2022.1134. [ABSTRACT FROM AUTHOR]

Background: Patients with Cushing's disease (CD) with hypercortisolism have an increased risk of opportunistic infection. However, most CD patients exposed to infections are diagnostic latency, leading to a poor prognosis. Methods: Six patients in our hospital and an additional six patients in the literature were included in this study. Clinical information of CD patients with pulmonary Cryptococcus neoformans are reviewed. Results: The average baseline total cortisol and ACTH in serum at 8 am of all the patients was 44.85 μg/dL (normal range 4.0–22.3 μg/dL) and 200.3 pg/mL (normal range 0–46 pg/mL), respectively. Lymphopenia was found in 2 out of 6 patients in our hospital. The pulmonary radiologic findings included nodules (4/12), masses with or without a cavity (5/12), infiltration (5/12), and consolidation (4/12). The diagnosis of C. neoformans was established by lung pathology results (7/12), microorganism culture (3/12), and serum cryptococcal polysaccharide antigen (4/12). Lung lobectomy was performed in two patients who had a nodule in one lung lobe. Antifungal drugs were administered, including amphotericin-B (7/12), fluconazole (4/12), flucytosine (2/12) and liposomal amphotericin (1/12). Additional therapies for CD included trans-sphenoidal pituitary adenoma surgery (9/12), adrenalectomy (1/12) and ketoconazole (2/12). Seven patients survived, and five patients died. Conclusion: Pulmonary C. neoformans is an uncommon but fatal opportunistic infection in CD patients. Pulmonary nodules or masses should be aggressively investigated to exclude the C. neoformans among CD patients. The infiltration lesions in chest CT scan and lymphopenia are associated with poor prognosis. Keywords: Cushing's disease, Lung, Cryptococcus neoformans