TASK DEFINITION: In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.
PROBLEM: Ebola virus (EBOV) disease can result in a range of symptoms anywhere from virtually asymptomatic to severe hemorrhagic fever during acute infection. Additionally, spans of asymptomatic persistence in recovering survivors is possible, during which transmission of the virus may occur. In acute infection, substantial cytokine storm and bystander lymphocyte apoptosis take place, resulting in uncontrolled, systemic inflammation in affected individuals. Recently, studies have demonstrated the presence of EBOV proteins VP40, glycoprotein (GP), and nucleoprotein (NP) packaged into extracellular vesicles (EVs) during infection. EVs containing EBOV proteins have been shown to induce apoptosis in recipient immune cells, as well as contain pro-inflammatory cytokines. In this manuscript, we review the current field of knowledge on EBOV EVs including the mechanisms of their biogenesis, their cargo and their effects in recipient cells. Furthermore, we discuss some of the effects that may be induced by EBOV EVs that have not yet been characterized and highlight the remaining questions and future directions. It is estimated that only approximately 20%-25% of GP products are the membrane-anchored GP 1,2 form, while the remaining 75%-80% are of the secreted type, with~70% sGP and~5% ssGP [7] [8] [9] [10] . During early infection, EBOV targets mainly monocytes/macrophages and dendritic cells (DCs). It is thought that these migrating cells aid in systemic dissemination of the virus throughout the host, especially into secondary lymphoid organs and the liver. Intense replication of the virus then takes place in other host cell types, including endothelial cells, epithelial cells, fibroblasts and hepatocytes [11] [12] [13] [14] . Fatal filovirus infections often involve severely dysregulated innate and adaptive immune responses, defective coagulation, and are typified by systemic cytokine storm and multi-organ failure. Immune system damage includes type-I and type-II interferon (IFN) antagonism by VP35 and VP24, respectively, NK and T-cell depletion known as bystander lymphocyte apoptosis, and impaired DC maturation [15] . Severe presentations of disease are accompanied by viral replication within and necrosis of the spleen, liver, kidneys, gonads, gastrointestinal tract and endocardium [13, 16] . In those who are fortunate enough to survive acute Ebola virus disease (EVD), the virus becomes undetectable in the blood, depicting a typical phenotype of viral clearance. However, either entire virus or viral components may remain detectable in patients relatively long after recovery, particularly in immune-privileged sites [17] [18] [19] [20] [21] [22] [23] [24] . Notably, recent studies have shown that over 1 in 4 male survivors from the 2016 outbreak contained virus within their semen up to 7-9 months past the disappearance of EVD symptoms. Furthermore, virus has still been detectable up to 16-18 months later [17] . This type of "clinical latency" or persistent infection has significance for public health in the following ways: (1) viral reservoirs within immune privileged sites have implications for reemergence and persistence of the virus within the infected individual, potentially allowing for resurgence of infection, morbidity, and mortality [25]; (2) these reservoirs may allow for the transmission of the virus to additional individuals long after initial infection, hindering efforts to control the spread of outbreaks by public health infrastructures [25]; and (3) significant political, socio-economic, and social stigma considerations must be taken into account for policies to support the normal life and travel of EVD survivors [26] [27] [28] [29] . Spread of the virus by this route is of particular concern, as several cases of sexual transmission from male to female have already been documented. One of the first such cases involved transmission from a man 6 months past his recovery to a woman in Liberia [30, 31] . To date, three additional "flare-ups" of EBOV by sexual contact have been determined, together accounting for approximately half of the eight mini-outbreaks caused by persistently infected survivors documented since 2016 [32] [33] [34] [35] . The most concerning of these cases occurred over 480 days (nearly 17 months) past the initial recovery of the patient [35] . To further complicate the matter, there have been multiple reports addressing potential asymptomatic or undiagnosed portions of the population. Previous studies have put the number of seropositive but undiagnosed/asymptomatic individuals anywhere between 0%-47% [36] [37] [38] [39] [40] [41] [42] [43] [44] . This of course implies that such individuals may represent an invisible source of viral transmission and future outbreaks. Exemplifying this is a case involving an asymptomatic mother who likely transmitted EBOV to her 9-month-old infant (as determined by sequencing and phylogenetic analysis) through breast milk, ultimately resulting in the fatality of the child [19] . Interestingly, the asymptomatic father's semen was also EBOV-positive, but was distantly related to the strains found in the mother and child. Currently, the mechanism of this viral persistence is not well characterized, although new studies have hinted as several possibilities, which will be discussed later. Extracellular vesicles (EVs) are small, membrane-bound vesicles that are released from numerous cell types and are involved in cell-to-cell communication. The intercellular communication is mediated by EV cargo, consisting of nucleic acids and proteins, which can be transferred between cells to elicit a phenotypic change in the recipient cell [45] [46] [47] . EVs are heterogeneous; as such, the current literature separates EVs into several different categories based mainly on differences in size and cellular origin, including subtypes such as exosomes and microvesicles [48] . Microvesicles bud directly from the plasma membrane and are generally larger than exosomes with diameters ranging from Viruses 2019, 11, 410 3 of 25

SOLUTION: viruses Extracellular Vesicles and Ebola Virus: A New Mechanism of Immune Evasion

PROBLEM: Background: We undertook a 2X2 factorial, randomized controlled trial (RCT) to assess whether vitamin D 3 supplementation (10,000 international units per week) versus placebo and gargling versus no gargling could prevent viral, clinical upper respiratory tract infection (URTI) in university students. Methods: We randomized 600 students into 4 treatment arms: 1) vitamin D 3 and gargling, 2) placebo and gargling, 3) vitamin D 3 and no gargling, and 4) placebo and no gargling. Students completed weekly electronic surveys and submitted self-collected mid-turbinate nasal flocked swabs during September and October in 2010 or 2011. Symptomatic students also completed an electronic symptom diary. The primary and secondary outcomes were the occurrence of symptomatic clinical URTI and laboratory confirmed URTI respectively. Results: Of 600 participants, 471 (78.5%) completed all surveys while 43 (7.2%) completed none; 150 (25.0%) reported clinical URTI. Seventy participants (23.3%) randomized to vitamin D 3 reported clinical URTI compared to 80 (26.7%) randomized to placebo (RR:0.79, CI 95 :0.61-1.03, p = 0.09). Eighty-five participants (28.3%) randomized to gargling reported clinical URTI compared to 65 participants (21.7%) randomized to the no gargling arm (RR:1.3, CI 95 :0.92-1.57, p = 0.19). Laboratory testing identified 70 infections (46.7 per 100 URTIs). Vitamin D 3 treatment was associated with a significantly lower risk for laboratory confirmed URTI (RR: 0.54, CI 95 :0.34-0.84, p = 0.007) and with a significantly lower mean viral load measured as log 10 viral copies/mL (mean difference: 0.89, CI 95: -1.7, 0.06, p = 0.04). Fewer students assigned to gargling experienced laboratory confirmed URTI, however this was not statistically significant (RR:0.82, CI 95 :0.53-1.26, p = 0.36). Conclusions: These results suggest that vitamin D 3 is a promising intervention for the prevention of URTI. Vitamin D 3 significantly reduced the risk of laboratory confirmed URTI and may reduce the risk of clinical infections. Trial registration: Clinical Trials Registration: NCT01158560.

SOLUTION: Vitamin D 3 and gargling for the prevention of upper respiratory tract infections: a randomized controlled trial

PROBLEM: The need to protect public health during the current COVID-19 pandemic has necessitated conference cancellations on an unprecedented scale. As the scientific community adapts to new working conditions, it is important to recognize that some of our actions may disproportionately affect early-career researchers and scientists from countries with limited research funding. We encourage all conference organizers, funders and institutions who are able to do so to consider how they can mitigate the unintended consequences of conference and travel cancellations and we provide seven recommendations for how this could be achieved. The proposed solutions may also offer long-term benefits for those who normally cannot attend conferences, and thus lead to a more equitable future for generations of researchers.

SOLUTION:
Mitigating the impact of conference and travel cancellations on researchers' futures