Miracle-dz/UniFAR-FTUs huggingface dataset:
Neural Extractive Summarization with Side Information

Most extractive summarization methods focus on the main body of the document from which sentences need to be extracted. However, the gist of the document may lie in side information, such as the title and image captions which are often available for newswire articles. We propose to explore side information in the context of single-document extractive summarization. We develop a framework for single-document summarization composed of a hierarchical document encoder and an attention-based extractor with attention over side information. We evaluate our model on a large scale news dataset. We show that extractive summarization with side information consistently outperforms its counterpart that does not use any side information, in terms of both informativeness and fluency.
Estimation of the Number of Women Living with Metastatic Breast Cancer in the United States

Background: Distant metastatic breast cancer (MBC), including metastases found at diagnosis (de novo) and those occurring later (recurrence), represents the most severe form of the disease, when resource utilization is most intensive. Yet, the number of women living with MBC in the United States is unknown. The objective of this article is to use population-based data to estimate the prevalence of MBC. Methods: We used a back-calculation method to estimate MBC prevalence from U.S. breast cancer mortality and survival from the Surveillance, Epidemiology and End Results (SEER) registries. On the basis of the illness–death process, this method assumes that each observed breast cancer death is the result of MBC, either de novo or a recurrence with metastatic disease. Results: We estimate that by January 1, 2017, there will be 154,794 women living with MBC in the United States, three in four initially diagnosed with stage I–III breast cancer who later progressed to MBC. Median survival and 5-year relative survival for de novo MBC increased over the years, especially in younger women. We estimate a two-fold increase in 5-year relative survival rate from 18% to 36%, for women diagnosed with de novo MBC at age 15–49 between 1992–1994 and 2005–2012, respectively. Conclusions: This study demonstrates an increasing number of women in the United States living with MBC, likely the result of improvements in treatment and aging of the U.S. population. Impact: The increasing burden of MBC highlights the importance of documenting recurrence to foster more research into the specific needs of this understudied population. Cancer Epidemiol Biomarkers Prev; 26(6); 809–15. ©2017 AACR.
Systems analysis in Cellvibrio japonicus resolves predicted redundancy of β‐glucosidases and determines essential physiological functions

Degradation of polysaccharides forms an essential arc in the carbon cycle, provides a percentage of our daily caloric intake, and is a major driver in the renewable chemical industry. Microorganisms proficient at degrading insoluble polysaccharides possess large numbers of carbohydrate active enzymes (CAZymes), many of which have been categorized as functionally redundant. Here we present data that suggests that CAZymes that have overlapping enzymatic activities can have unique, non‐overlapping biological functions in the cell. Our comprehensive study to understand cellodextrin utilization in the soil saprophyte Cellvibrio japonicus found that only one of four predicted β‐glucosidases is required in a physiological context. Gene deletion analysis indicated that only the cel3B gene product is essential for efficient cellodextrin utilization in C. japonicus and is constitutively expressed at high levels. Interestingly, expression of individual β‐glucosidases in Escherichia coli K‐12 enabled this non‐cellulolytic bacterium to be fully capable of using cellobiose as a sole carbon source. Furthermore, enzyme kinetic studies indicated that the Cel3A enzyme is significantly more active than the Cel3B enzyme on the oligosaccharides but not disaccharides. Our approach for parsing related CAZymes to determine actual physiological roles in the cell can be applied to other polysaccharide‐degradation systems.
PD-L1 protein expression assessed by immunohistochemistry is neither prognostic nor predictive of benefit from adjuvant chemotherapy in resected non-small cell lung cancer

Background The expression of programmed death (PD) ligand 1 (PD-L1) protein expression assessed by immunohistochemistry (IHC) has been correlated with response and survival benefit from anti-PD-1/PD-L1 immune checkpoint inhibitor therapies in advanced non-small cell lung carcinoma (NSCLC). The efficacy of several agents appears correlated with PD-L1 expression. It remains controversial whether PD-L1 is prognostic in NSCLC. We assessed the prognostic value of PD-L1 IHC and its predictive role for adjuvant chemotherapy in early stage NSCLC. Patients and methods Tumor sections from three pivotal adjuvant chemotherapy trials (IALT, JBR.10, CALGB 9633) using the E1L3N antibody were studied in this pooled analysis. PD-L1 staining intensity and percentage in both tumor cells (TCs) and immune cells (ICs) were scored by two pathologists. The average or consensus PD-L1 expression levels across intensities and/or percent cells stained were correlated with clinicopathological and molecular features, patient survivals and potential benefit of adjuvant chemotherapy. Results Results from 982 patients were available for analysis. Considering staining at any intensities for overall PD-L1 expression, 314 (32.0%), 204 (20.8%) and 141 (14.3%) tumor samples were positive for PD-L1 staining on TCs using cut-offs at ≥1%, ≥10% and ≥25%, respectively. For PD-L1 expressing ICs, 380 (38.7%), 308 (31.4%) and 148 (15.1%) were positive at ≥ 1%, ≥10% and 25% cut-offs, respectively. Positive PD-L1 was correlated with squamous histology, intense lymphocytic infiltrate, and KRAS but not with TP53 mutation. EGFR mutated tumors showed statistically non-significant lower PD-L1 expression. PD-L1 expression was neither prognostic with these cut-offs nor other exploratory cut-offs, nor were predictive for survival benefit from adjuvant chemotherapy. Conclusions PD-L1 IHC is not a prognostic factor in early stage NSCLC patients. It is also not predictive for adjuvant chemotherapy benefit in these patients.
An optimal operating strategy for fixed-bed bioreactors used in wastewater treatment.

Optimization of a fixed-bed bioreactor used in wastewater treatment is addressed. The objective of optimization is to maximize the treatment efficiency of the biofilter by manipulating the feed flow rate while satisfying operational constraints. Numerical results indicate that the optimal input is characterized as being on the boundary of the admissible region. Thus, the characterized optimal solution is implemented using a simple feedback control law, which provides the optimal input profile despite variations in substrate inlet concentration and biomass growth rate.
Chikungunya Virus Overcomes Polyamine Depletion by Mutation of nsP1 and the Opal Stop Codon To Confer Enhanced Replication and Fitness

ABSTRACT Polyamines, which are small positively charge molecules present in all cells, play important roles in the replication of DNA and RNA viruses. Chikungunya virus (CHIKV) relies on polyamines for translation of the viral genome upon viral entry, and pharmacological depletion of polyamines limits viral replication. However, the potential development of antiviral resistance necessitates a better understanding of how polyamines function and can be targeted via compounds that alter polyamine levels. We have isolated CHIKV that is resistant to polyamine depletion and contains two mutations in the nonstructural protein 1 (nsP1)-coding region in combination with a mutation to the opal stop codon preceding nsP4. These mutations, in addition to promoting viral replication in polyamine-depleted cells, confer enhanced viral replication in vitro and in vivo. The nsP1 mutations enhance membrane binding and methyltransferase activities, while the stop codon mutation allows increased downstream translation. These mutations, when combined, enhance viral fitness, but individual mutants are attenuated in mosquitoes. Together, our results suggest that CHIKV can evolve resistance to polyamine depletion and that pharmaceuticals targeting the polyamine biosynthetic pathway may be best used in combination with other established antivirals to mitigate the development of resistance. IMPORTANCE Chikungunya virus is a mosquito-borne virus that has infected millions worldwide. Its expansion into the Americas and rapid adaptation to new mosquito hosts present a serious threat to human health, which we can combat with the development of antiviral therapies as well as understanding how these viruses will mutate when exposed to antiviral therapies. Targeting polyamines, small positively charged molecules in the cell, may be a potential strategy against RNA viruses, including chikungunya virus. Here, we have described a virus that is resistant to polyamine depletion and has increased fitness in cells and in full organisms. Mutations in viral genome capping machinery, membrane binding activity, and a stop codon arise, and their altered activities enhance replication in the absence of polyamines. These results highlight strategies by which chikungunya virus can overcome polyamine depletion and emphasize continued research on developing improved antiviral therapies.
Pathogenic Events in a Nonhuman Primate Model of Oral Poliovirus Infection Leading to Paralytic Poliomyelitis

ABSTRACT Despite a great deal of prior research, the early pathogenic events in natural oral poliovirus infection remain poorly defined. To establish a model for study, we infected 39 macaques by feeding them single high doses of the virulent Mahoney strain of wild type 1 poliovirus. Doses ranging from 107 to 109 50% tissue culture infective doses (TCID50) consistently infected all the animals, and many monkeys receiving 108 or 109 TCID50 developed paralysis. There was no apparent difference in the susceptibilities of the three macaque species (rhesus, cynomolgus, and bonnet) used. Virus excretion in stool and nasopharynges was consistently observed, with occasional viremia, and virus was isolated from tonsils, gut mucosa, and draining lymph nodes. Viral replication proteins were detected in both epithelial and lymphoid cell populations expressing CD155 in the tonsil and intestine, as well as in spinal cord neurons. Necrosis was observed in these three cell types, and viral replication in the tonsil/gut was associated with histopathologic destruction and inflammation. The sustained response of neutralizing antibody correlated temporally with resolution of viremia and termination of virus shedding in oropharynges and feces. For the first time, this model demonstrates that early in the infectious process, poliovirus replication occurs in both epithelial cells (explaining virus shedding in the gastrointestinal tract) and lymphoid/monocytic cells in tonsils and Peyer's patches (explaining viremia), extending previous studies of poliovirus pathogenesis in humans. Because the model recapitulates human poliovirus infection and poliomyelitis, it can be used to study polio pathogenesis and to assess the efficacy of candidate antiviral drugs and new vaccines. IMPORTANCE Early pathogenic events of poliovirus infection remain largely undefined, and there is a lack of animal models mimicking natural oral human infection leading to paralytic poliomyelitis. All 39 macaques fed with single high doses ranging from 107 to 109 TCID50 Mahoney type 1 virus were infected, and many of the monkeys developed paralysis. Virus excretion in stool and nasopharynges was consistently observed, with occasional viremia; tonsil, mesentery lymph nodes, and intestinal mucosa served as major target sites of viral replication. For the first time, this model demonstrates that early in the infectious process, poliovirus replication occurs in both epithelial cells (explaining virus shedding in the gastrointestinal tract) and lymphoid/monocytic cells in tonsils and Peyer's patches (explaining viremia), thereby supplementing historical reconstructions of poliovirus pathogenesis. Because the model recapitulates human poliovirus infection and poliomyelitis, it can be used to study polio pathogenesis, candidate antiviral drugs, and the efficacy of new vaccines.
Design, Simulation and Characterization of Compliant Microfluidic Devices

A new technique has been developed to make valves and other microfluidic structures by patterned welding of compliant thermoplastic films. Electrical contacts, packaging, and low leakage connections with external tubing to these structures have also been demonstrated. An electrostatically driven normally open microvalve made of thermoplastic materials is presented. The microvalves are compatible with a wide range of fluids. The microvalve is limited to actuation voltages less than 600 V because of the breakdown voltage limitation of 1.4 µm thick Mylar film. The pressure range is limited by the value of the closing voltages to few kPa, although the valve can withstand much higher applied pressures (~20 kPa). The operating temperature should be limited to 100 oC because of the low melting point of the LLDPE tubing and support rings. The measured leak rate for well manufactured microvalves was less than 10% of the flow rate. The proposed fabrication method for welding very thin polyester sheets is used to produce several types of micromixers and demonstrate its potential use for producing different designs of mixer structures that can be modified as needed without the need for a photolithography or microfabrication facilities. The proposed fabrication technique is applicable for the design of the planar microfluidic devices.
Losartan for the nephropathy of sickle cell anemia: A phase‐2, multicenter trial

Nephropathy is a common and progressive complication of sickle cell anemia (SCA). In SCA mice, we found that hyperangiotensinemia in the absence of hypertension underlies nephropathy, and its downregulation by losartan, an angiotensin‐II‐receptor‐1 blocker, reduced albuminuria and progression of nephropathy. Therefore, we performed a phase‐2 trial of oral losartan, given for 6 months, to explore whether it reduced albuminuria in children and adults with SCA. Participants were allocated to groups defined by class of baseline urinary albumin‐to‐creatinine ratio (UACR): no albuminuria (NoA), microalbuminuria (MicroA), and macroalbuminuria (MacroA). The primary endpoint was a ≥25% reduction UACR from baseline. There were 32 evaluable participants (mean age 24 years; NoA = 14, MicroA = 12, MacroA = 6). The primary endpoint was met in 83% of the MacroA group (P < 0.0001) and 58% of the MicroA group (P < 0.0001). Median fold‐change in UACR was −0.74 for MacroA and −0.46 for MicroA. In MacroA and MicroA, UACR classification improved in 50% but worsened in 11%. Urine osmolality and estimated glomerular filtration rate (eGFR) did not change significantly. Losartan was discontinued in three participants [leg cramps, N = 1; decline in eGFR >25% (142➝104 mL/minute/1.73 m2), N = 1; rise in serum creatinine >50% (0.2➝0.3 mg/dL), N = 1]. Albuminuria was associated with diastolic dysfunction and impaired functional capacity, although cardiopulmonary status was unchanged after 6 months of losartan therapy. In summary, losartan decreased urinary albumin excretion in most participants with albuminuria. Those with macroalbuminuria had the greatest benefit. This study forms the basis for a phase‐3, randomized, placebo‐controlled trial of losartan for the nephropathy of SCA.
Study of Uptake of Pb and Cd by Three Nutritionally Important Indian Vegetables Grown in Artificially Contaminated Soils of Mumbai, India

The ability of nutritionally important vegetable species as heavy metal accumulators was assessed. The root, stem and leaf content of the two metals lead and cadmium in the three plant varieties Spinach (Spinaciaoleracea), Fenugreek (Trigonellafoenum-graecum) and Red Amaranth (Amaranthuscruentus) was determined using pot experiments. Metal analysis was done using AAS. The metal concentration in different tissues varied according to plant part, type of metal, soil properties, morphological differences in plants, physiological differences in terms of heavy metal content, omission, increased uptake, foliarabsorption, etc. Highest metal concentration was reported in roots of all three plant varieties. Red Amaranth and Spinach showed higher tendency to accumulate lead and cadmium respectively. Among the two metals, Pb was accumulated more than Cd indicating plant affinity towards Pb. Transfer factor index also gave supporting values. None of the transfer factor exceeded 1 showing that none of the three species are hyperaccumulators. But they are certainly accumulating metals in its tissues. The root to shoot translocation factors concluded that metals are getting retained in roots and minimum levels are getting transferred in shoot parts. This indicates that roots which are insignificant for dietary intake of humans contain maximum quantities of heavy metal. Whereas the leaves that are nutritionally important for humans accumulate low levels of metals. Lead concentration in leaves of Red Amaranth and Spinach exceeded Indian standards. While lead concentration in Fenugreek and cadmium concentration in all the three vegetables was detected to be within the prescribed limits. This shows that elevated levels of Cd in soil may not add it significantly in human food chain but the same for Pb may raise its concentration in plants thereby increasing its toxicity.
Paper physics: Fractionation of microfibrillated cellulose and its effects on tensile index and elongation of paper

In this work we examine the fractionation of microfibrillated cellulose (MFC) and its effect on the physical properties of paper. In the first part of this work, we evaluate the fractionation of commercially available MFC using multiple stages of traditional fractionation unit operations, namely a hydrocyclone, a pressure screen, and a novel technique based upon the control of the threshold for motion in a weak gel. The results indicate that a smaller fibre length average fraction could be obtained using the gel separation technique than using multiple stages of separation in both the hydrocyclone and the pressure screen. With the gel technique we were able to reduce the average fibre length of the MFC from 221 µm to 100 µm. In the second part of the work, composite paper samples were formed by addition of fractionated and non-fractionated MFC to chemical wood fibres and the strength of the resulting composites were studied. The results showed 25% improvement in tensile index by addition of MFC and an additional 10% improvement in tensile strength by addition of fractionated MFC using the gel technique.
In Vivo and in Vitro Proteome Analysis of Human Immunodeficiency Virus (HIV)-1-infected, Human CD4+ T Cells*

Host-directed therapies against HIV-1 are thought to be critical for long term containment of the HIV-1 pandemic but remain elusive. Because HIV-1 infects and manipulates important effectors of both the innate and adaptive immune system, identifying modulations of the host cell systems in humans during HIV-1 infection may be crucial for the development of immune based therapies. Here, we quantified the changes of the proteome in human CD4+ T cells upon HIV-1 infection, both in vitro and in vivo. A SWATH-MS approach was used to measure the proteome of human primary CD4+ T cells infected with HIV-1 in vitro as well as CD4+ T cells from HIV-1-infected patients with paired samples on and off antiretroviral treatment. In the in vitro experiment, the proteome of CD4+ T cells was quantified over a time course following HIV-1 infection. 1,725 host cell proteins and 4 HIV-1 proteins were quantified, with 145 proteins changing significantly during the time course. Changes in the proteome peaked 24 h after infection, concomitantly with significant HIV-1 protein production. In the in vivo branch of the study, CD4+ T cells from viremic patients and those with no detectable viral load after treatment were sorted, and the proteomes were quantified. We consistently detected 895 proteins, 172 of which were considered to be significantly different between the viremic patients and patients undergoing successful treatment. The proteome of the in vitro-infected CD4+ T cells was modulated on multiple functional levels, including TLR-4 signaling and the type 1 interferon signaling pathway. Perturbations in the type 1 interferon signaling pathway were recapitulated in CD4+ T cells from patients. The study shows that proteome maps generated by SWATH-MS indicate a range of functionally significant changes in the proteome of HIV-infected human CD4+ T cells. Exploring these perturbations in more detail may help identify new targets for immune based interventions.
Histopathological Characterization and Whole Exome Sequencing of Ectopic Thyroid: Fetal Architecture in a Functional Ectopic Gland from Adult Patient

Ectopic thyroid results from a migration defect of the developing gland during embryogenesis causing congenital hypothyroidism. But it has also been detected in asymptomatic individuals. This study aimed to investigate the histopathological, functional, and genetic features of human ectopic thyroids. Six samples were histologically examined, and the expression of the specific thyroid proteins was assessed by immunohistochemistry. Two samples were submitted to whole exome sequencing. An oropharynx sample showed immature fetal architecture tissue with clusters or cords of oval thyrocytes and small follicles; one sample exhibited a normal thyroid pattern while four showed colloid goiter. All ectopic thyroids expressed the specific thyroid genes and T4 at similar locations to those observed in normal thyroid. No somatic mutations associated with ectopic thyroid were found. This is the first immature thyroid fetal tissue observed in an ectopic thyroid due to the arrest of structural differentiation early in the colloid stage of development that proved able to synthesize thyroid hormone but not to respond to TSH. Despite the ability of all ectopic thyroids to synthetize specific thyroid proteins and T4, at some point in life, it may be insufficient to support body growth leading to hypothyroidism, as observed in some of the patients.
Passive acquired mucosal immunity to group A streptococci by secretory immunoglobulin A

We present a model in which animals are passively immunized at a mucosal site, allowing one to evaluate immunological protection at the mucosal level only. Affinity-purified, anti-M protein sIgA administered intranasally protected mice against systemic infection after intranasal challenge with group A streptococci. In contrast, anti-M protein serum Ig administered intranasally was not protective at this site, although it neutralized the antiphagocytic property of M protein and promoted phagocytosis. Protection by sIgA occurred despite the lower immunoreactivity of sIgA to purified M protein compared with serum Ig. The data suggest that sIgA can protect at the mucosa and may preclude the need for opsonic IgG in preventing streptococcal infection.