Miracle-dz/UniFAR-FTUs huggingface dataset:
Primary meningeal anaplastic largecell lymphoma

Sir, Anaplastic large cell lymphoma (ALCL) is an aggressive lymphoid malignancy. Primary involvement of the central nervous system is extremely uncommon with only nine cases reported since 1988. The majority of these have been in children. A case of ALK-negative, null cell type ALCL, involving the tentorium cerebelli, in an elderly woman is presented. An 82-year-old woman presented with lower cranial nerve signs of approximately three months duration. Magnetic resonance imaging (MRI) showed a contrastenhancing lesion attached to the tentorium cerebelli and compressing the brainstem (Fig. 1). A radiological diagnosis of meningioma was made. A full blood examination showed no abnormality. The patient underwent posterior fossa craniotomy and decompression. Craniotomy generated fragments of a densely hypercellular tumour composed of large, pleomorphic, often multinucleated cells mixed with small mature lymphocytes (Fig. 2A). In some areas, collections of eosinophils were identified. Broad bands of mature collagen were seen in some areas giving the tumour a vaguely nodular appearance. The large cells were strongly immunoreactive for CD30 (Fig. 2B), but were negative for the T lymphocyte marker, CD3. The majority of the small cells showed CD3 immunoreactivity.ModeratenumbersofCD68zmonocyte– macrophages were identified. No ALK-1 reactivity was seen. Epstein–Barr virus DNA could not be detected by polymerase chain reaction performed on formalin-fixed, paraffin-embedded tissue. A VP shunt, to relieve hydrocephalus, was inserted at the time of decompression of the meningeal tumour. Postoperative MRIs of the abdomen and chest as well as bone marrow trephine showed no evidence of systemic disease. The patient refused chemotherapy and died 6 weeks after surgery. A post mortem was not performed. Anaplastic large cell lymphoma (ALCL) is an aggressive, rare form of non-Hodgkin’s lymphoma usually affecting children and young adults. There is a 6:1 male preponderance in the second and third decades. The disease has both nodal and extranodal manifestations. Common extranodal sites include skin, bone (solitary or multiple lesions), soft tissues, lung and liver. The central nervous system is rarely involved. Identification of ALCL arose out of attempts, in the early 1980s, to find antigens specific for Hodgkin’s disease, in particular for Reed– Sternberg cells. Proliferation of large irregular, often multinucleated cells with abundant cytoplasm and surface and perinuclear CD30 immunoreactivity is characteristic of ALCL. CD30 was initially called Ki-1 and these tumours were originally known as ‘Ki-1 large cell lymphomas’. CD30 is known to be a member of the nerve growth factor/tumour necrosis factor receptor (TNFR) superfamily of proteins. The protein is rich in cysteine residues, but its precise biological function is unknown. Multinucleated CD30z cells may be confused with Reed–Sternberg cells, but the large numbers Fig. 1 MRI showing a contrast-enhancing lesion attached to tentorium cerebelli (white arrow).
The Influence of Virtual Agents on Player Experience and Performance

This paper contributes a systematic research approach as well as findings of an empirical study conducted to investigate the effect of virtual agents on task performance and player experience in digital games. As virtual agents are supposed to evoke social effects similar to real humans under certain conditions, the basic social phenomenon social facilitation is examined in a testbed game that was specifically developed to enable systematical variation of single impact factors of social facilitation. Independent variables were the presence of a virtual agent (present vs. not present) and the output device (ordinary monitor vs. head-mounted display). Results indicate social inhibition effects, but only for players using a head-mounted display. Additional potential impact factors and future research directions are discussed.
Specific Gene Silencing by Artificial MicroRNAs in Physcomitrella patens: An Alternative to Targeted Gene Knockouts1[C][W][OA]

MicroRNAs (miRNAs) are approximately 21-nucleotide-long RNAs processed from nuclear-encoded transcripts, which include a characteristic hairpin-like structure. MiRNAs control the expression of target transcripts by binding to reverse complementary sequences directing cleavage or translational inhibition of the target RNA. Artificial miRNAs (amiRNAs) can be generated by exchanging the miRNA/miRNA* sequence within miRNA precursor genes, while maintaining the pattern of matches and mismatches in the foldback. Thus, for functional gene analysis, amiRNAs can be designed to target any gene of interest. The moss Physcomitrella patens exhibits the unique feature of a highly efficient homologous recombination mechanism, which allows for the generation of targeted gene knockout lines. However, the completion of the Physcomitrella genome necessitates the development of alternative techniques to speed up reverse genetics analyses and to allow for more flexible inactivation of genes. To prove the adaptability of amiRNA expression in Physcomitrella, we designed two amiRNAs, targeting the gene PpFtsZ2-1, which is indispensable for chloroplast division, and the gene PpGNT1 encoding an N-acetylglucosaminyltransferase. Both amiRNAs were expressed from the Arabidopsis (Arabidopsis thaliana) miR319a precursor fused to a constitutive promoter. Transgenic Physcomitrella lines harboring the overexpression constructs showed precise processing of the amiRNAs and an efficient knock down of the cognate target mRNAs. Furthermore, chloroplast division was impeded in PpFtsZ2-1-amiRNA lines that phenocopied PpFtsZ2-1 knockout mutants. We also provide evidence for the amplification of the initial amiRNA signal by secondary transitive small interfering RNAs, although these small interfering RNAs do not seem to have a major effect on sequence-related mRNAs, confirming specificity of the amiRNA approach.
Temporal evolution of main ambient PM 2. 5 sources in Santiago, Chile, from 1998 to 2012

Abstract. The inhabitants of Santiago, Chile have been exposed to harmful levels of air pollutants for decades. The city's poor air quality is a result of steady economic growth, and stable atmospheric conditions adverse to mixing and ventilation that favor the formation of oxidants and secondary aerosols. Identifying and quantifying the sources that contribute to the ambient levels of pollutants is key for designing adequate mitigation measures. Estimating the evolution of source contributions to ambient pollution levels is also paramount to evaluating the effectiveness of pollution reduction measures that have been implemented in recent decades. Here, we quantify the main sources that have contributed to fine particulate matter (PM2. 5) between April 1998 and August 2012 in downtown Santiago by using two different source-receptor models (PMF 5.0 and UNMIX 6.0) that were applied to elemental measurements of 1243 24 h filter samples of ambient PM2.5. PMF resolved six sources that contributed to ambient PM2. 5, with UNMIX producing similar results: motor vehicles (37.3 ± 1.1 %), industrial sources (18.5 ± 1.3 %), copper smelters (14.4 ± 0.8 %), wood burning (12.3 ± 1.0 %), coastal sources (9.5 ± 0.7 %) and urban dust (3.0 ± 1.2 %). Our results show that over the 15 years analyzed here, four of the resolved sources significantly decreased [95 % confidence interval]: motor vehicles 21.3 % [2.6, 36.5], industrial sources 39.3 % [28.6, 48.4], copper smelters 81.5 % [75.5, 85.9], and coastal sources 58.9 % [38.5, 72.5], while wood burning did not significantly change and urban dust increased by 72 % [48.9, 99.9]. These changes are consistent with emission reduction measures, such as improved vehicle emission standards, cleaner smelting technology, introduction of low-sulfur diesel for vehicles and natural gas for industrial processes, public transport improvements, etc. However, it is also apparent that the mitigation expected from the above regulations has been partially offset by the increasing amount of private vehicle use in the city, with motor vehicles becoming the dominant source of ambient PM2. 5 in recent years. Consequently, Santiago still experiences ambient PM2. 5 levels above the annual and 24 h Chilean and World Health Organization standards, and further regulations are required to reach ambient air quality standards.
Effects of Glucose and Starch on Lactate Production by Newly Isolated Streptococcus bovis S1 from Saanen Goats

ABSTRACT When ruminants are fed high-concentrate diets, Streptococcus bovis proliferates rapidly and produces lactate, potentially causing rumen acidosis. Understanding the regulatory mechanisms of the metabolism of this species might help in developing dietary strategies to alleviate rumen acidosis. S. bovis strain S1 was newly isolated from the ruminal fluid of Saanen dairy goats and then used to examine the effects of glucose and starch on bacterial metabolism and gene regulation of the organic acid-producing pathway in cultures at a pH of 6.5. Glucose or starch was added to the culture medium at 1 g/liter, 3 g/liter (close to a normal range in the rumen fluid), or 9 g/liter (excessive level). Lactate was the dominant acid produced during the fermentation, and levels increased with the amount of glucose or starch in a dose-dependent manner (P < 0.001). The production of formate and acetate in the fermentation media fluctuated slightly with the dose but accounted for small fractions of the total acids. The activities of lactate dehydrogenase (LDH) and α-amylase (α-AMY) increased with the starch dose (P < 0.05), but the α-AMY activity did not change with the glucose dose. The relative expression levels of the genes ldh, pfl (encoding pyruvate formate lyase), ccpA (encoding catabolite control protein A), and α-amy were higher at a dose of 9 g/liter than at 1 g/liter (P < 0.05). Expression levels of pfl and α-amy genes were higher at 3 g/liter than at 1 g/liter (P < 0.05). The fructose 1,6-diphosphate (FDP) concentration tended to increase with the glucose and starch concentrations. In addition, the S. bovis S1 isolate fermented glucose much faster than starch. We conclude that the quantities of glucose and soluble starch had a major effect on lactate production due to the transcriptional regulation of metabolic genes. IMPORTANCE This work used a newly isolated S. bovis strain S1 from the rumen fluid of Saanen goats and examined the effects of glucose and soluble starch on organic acid patterns, enzyme activity, and expression of genes for in vitro fermentation. It was found that lactate was the dominant product from S. bovis strain S1, and the quantities of both glucose and starch in the medium were highly correlated with lactate production and with the corresponding changes in associated enzymes and genes. Therefore, manipulating the metabolic pathway of S. bovis to alter the dietary level of readily fermentable sugar and carbohydrates may be a strategy to alleviate rumen acidosis.
Reply to reviewer #1

GENERAL The entire abstract will need to be rewritten in view of the results contained in the DOIs listed at the end of this review. It reflects omissions and mistaken assumptions listed in the detailed commentary that follows. The scaling of variance has to recognise that the variance of atmospheric variables obtained by observations acquired by adequate measurement techniques does not converge. That is one of several relevant results obtained by the finding that atmospheric variables have non-Gaussian probability distributions, with fat-tailed power laws best represented by Lévy statistics. The zoo of scaling behaviours displayed in this manuscript arises from this basic fact and its consequences. These facts have to be at least recognised as being in existence rather than simply ignored as in the present manuscript.
Mechanistic Studies of Antiproliferative Effects of Salvia triloba and Salvia dominica (Lamiaceae) on Breast Cancer Cell Lines (MCF7 and T47D)

Abstract Ethanol extracts obtained from two Salvia species, S. triloba and S. dominica, collected from the flora of Jordan, were evaluated for their antiproliferative activity against MCF7 and T47D breast cancer cell lines by the sulforhodamine B assay. The ethanol extracts were biologically active with IC50 values of (29.89 ±0.92) and (38.91 ±2.44) μg/mL for S. triloba against MCF7 and T47D cells, respectively, and (5.83 ±0.51) and (12.83 ±0.64) μg/mL for S. dominica against MCF7 and T47D cells, respectively. Flow cytometry analysis and the annexinV-propidium iodide (PI) assay revealed apoptosismediated, and to a lesser extent necrosis-induced, cell death by the S. triloba and S. dominica ethanolic extracts in T47D cells. The mechanism of apoptosis was further investigated by determining the levels of p53, p21/WAF1, FasL (Fas ligand), and sFas (Fas/APO-1). The extract from S. triloba induced a more pronounced enrichment in cytoplasmic mono- and oligonucleosomes than that from S. dominica (p < 0:05) in T47D cells. In response to the extract from S. dominica, but not from S. triloba, the proapoptotic efficacy was specifically regulated by p21. Extracts from both Salvia spp. did not enhance p53 levels, and apoptosis induced by them was not caspase-8- or sFas/FasL-dependent. Thus, our findings indicate that S. triloba and S. dominica ethanolic extracts may be useful in breast cancer management/treatment via proapoptotic cytotoxic mechanisms.
Detection of Human Bocavirus Species 2 and 3 in Bivalve Shellfish in Italy

ABSTRACT Human bocavirus (HBoV) has been shown to be a common cause of respiratory infections and gastroenteritis in children. Recently, HBoVs have been detected in sewage and river waters in Italy and worldwide. However, studies on their presence in other water environments and in bivalve mollusks are not yet available. In this study, 316 bivalve shellfish samples collected in three Italian regions over a 6-year period (2012 to 2017) were analyzed by nested PCR and sequencing using broad-range primer pairs targeting the capsid proteins VP1 and VP2 of HBoV. The virus was detected in 27 samples (8.5% of the total samples), and a statistically significant difference was found within the three regions. A further 13 samples, collected in geographic and temporal proximity to positive samples, were included in the study to assess the spread of HBoV in shellfish production areas at the time of contamination. Twelve of these additional samples were found to be positive for HBoV. All positive samples in this study were characterized as HBoV species 2 (17 samples; 8 different sequences) or species 3 (22 samples; 4 different sequences). This study reports the occurrence of HBoV in bivalve shellfish and shows evidence of considerable spatial spread of the virus throughout shellfish production areas. Further studies are needed to elucidate both the role of HBoV as an agent of gastroenteritis and the risk for foodborne transmission of this virus. IMPORTANCE Human bocavirus is recognized as an important cause of acute respiratory tract infections and has recently been considered an etiological agent of gastroenteritis in the pediatric population. Our findings document that HBoVs are detected in bivalve shellfish with a relevant prevalence and suggest that an assessment of the risk for foodborne transmission of these viruses should be undertaken.
Limits for Rumor Spreading in stochastic populations

Biological systems can share and collectively process information to yield emergent effects, despite inherent noise in communication. While man-made systems often employ intricate structural solutions to overcome noise, the structure of many biological systems is more amorphous. It is not well understood how communication noise may affect the computational repertoire of such groups. To approach this question we consider the basic collective task of rumor spreading, in which information from few knowledgeable sources must reliably flow into the rest of the population. In order to study the effect of communication noise on the ability of groups that lack stable structures to efficiently solve this task, we consider a noisy version of the uniform PULL model. We prove a lower bound which implies that, in the presence of even moderate levels of noise that affect all facets of the communication, no scheme can significantly outperform the trivial one in which agents have to wait until directly interacting with the sources. Our results thus show an exponential separation between the uniform PUSH and PULL communication models in the presence of noise. Such separation may be interpreted as suggesting that, in order to achieve efficient rumor spreading, a system must exhibit either some degree of structural stability or, alternatively, some facet of the communication which is immune to noise. We corroborate our theoretical findings with a new analysis of experimental data regarding recruitment in Cataglyphis niger desert ants.
Estimation of sodium and potassium intakes assessed by two 24 h urine collections in healthy Japanese adults: a nationwide study

Excess Na intake and insufficient K intake are well-known risk factors for CVD. International comparative studies have reported that Japan has the highest intake of Na and the lowest intake of K in the world. However, no recent study has precisely assessed Na and K intakes in Japanese adults. In the present study, Na and K intakes were estimated from two 24 h urine collections implemented in twenty-three out of forty-seven prefectures in Japan. Apparently healthy men (n 384) and women (n 376), aged 20 to 69 years, who had been working in welfare facilities were recruited, with data collection conducted in February and March 2013. The mean Na excretion was 206·0 mmol/d in men and 173·9 mmol/d in women. The respective values of K excretion were 51·6 and 47·2 mmol/d. The excretion of both Na and K varied considerably among the prefectures, and was higher in subjects with a higher BMI. In contrast, only K excretion was associated with age. After estimating the usual intakes of Na and K, it was found that none of the male subjects met the recommended Na intake values of the WHO, and that only 3·2 % met those of the Japanese government. The respective values for females were 0·1 and 5·0 %. For K intake, 7·5 % of the total subjects met the recommended values of the WHO and 21·7 % met those of the Japanese government. These findings suggest that there is an urgent need for the development of an effective intervention programme to reduce Na intake and promote K intake in the Japanese population.
The safety and efficacy of sunitinib before planned nephrectomy in metastatic clear cell renal cancer

Background: The safety and efficacy of upfront sunitinib, before nephrectomy in metastatic clear cell renal cancer (mCRC), has not been prospectively evaluated. Methods: Two prospective single-arm phase II studies investigated either two cycles (study A: n = 19) or three cycles (study B: n = 33) of sunitinib before nephrectomy in mCRC. Results: Overall, 38 of 52 (73%) of patients obtained clinical benefit (by RECIST) before surgery. The partial response rate of the primary tumour was 6% [median reduction in longest diameter of 12% (range 8%−35%)]. No patients became ineligible due to local progression of disease. A nephrectomy was carried out in 37 (71%) of patients. Necrosis (>50%) was a prominent feature at nephrectomy in 49%. Surgical complications (Clavien–Dindo classification) occurred in 10 (27%) patients, including one death (3%). The median blood loss and surgical time were 725 (90–4200) ml and 189 (70–420) min, respectively. The median progression-free survival was 8 months (95% confidence interval 6–15 months). A comparison of two versus three pre-surgery cycles showed no significant difference in terms of surgical complications or efficacy. Conclusions: Nephrectomy after upfront sunitinib can be carried out safely. It obtains control of disease. Randomised studies are required to address if this approach is beneficial.
Cooperative but distinct early co-signaling events originate from ERBB2 and ERBB1 receptors upon trastuzumab treatment in breast cancer cells

ERBB2 receptor belongs to the ERBB tyrosine kinase receptor family. At variance to the other family members, ERBB2 is a constitutively active orphan receptor. Upon ligand binding and activation, ERBB receptors form homo- or hetero-dimers with the other family members, including ERBB2, promoting an intracellular signaling cascade. ERBB2 is the preferred dimerization partner and ERBB2 heterodimers signaling is stronger and longer acting compared to heterodimers between other ERBB members. The specific contribution of ERBB2 in heterodimer signaling is still undefined. Here we report the formation of circular dorsal ruffles (CDRs) upon treatment of the ERBB2-overexpressing breast cancer cell lines SK-BR-3 and ZR751 with Trastuzumab, a therapeutic humanized monoclonal antibody directed against ERBB2. We found that in SK-BR-3 cells Trastuzumab leads to surface redistribution of ERBB2 and ERBB1 in CDRs, and that the ERBB2-dependent ERK1/2 phosphorylation and ERBB1 expression are both required for CDR formation. In particular, in these cells CDR formation requires activation of both the protein regulator of actin polymerization N-WASP, mediated by ERK1/2, and of the actin depolymerizing protein cofilin, mediated by ERBB1. Furthermore, we suggest that this latter event may be inhibited by the negative cell motility regulator p140Cap, as we found that p140Cap overexpression led to cofilin deactivation and inhibition of CDR formation. In conclusion, here we show for the first time an ERBB2-specific signaling contribution to an ERBB2/ERBB1 heterodimer, in the activation of a complex biological process such as the formation of CDRs.
All your face are belong to us: breaking Facebook's social authentication

Two-factor authentication is widely used by high-value services to prevent adversaries from compromising accounts using stolen credentials. Facebook has recently released a two-factor authentication mechanism, referred to as Social Authentication, which requires users to identify some of their friends in randomly selected photos. A recent study has provided a formal analysis of social authentication weaknesses against attackers inside the victim's social circles. In this paper, we extend the threat model and study the attack surface of social authentication in practice, and show how any attacker can obtain the information needed to solve the challenges presented by Facebook. We implement a proof-of-concept system that utilizes widely available face recognition software and cloud services, and evaluate it using real public data collected from Facebook. Under the assumptions of Facebook's threat model, our results show that an attacker can obtain access to (sensitive) information for at least 42% of a user's friends that Facebook uses to generate social authentication challenges. By relying solely on publicly accessible information, a casual attacker can solve 22% of the social authentication tests in an automated fashion, and gain a significant advantage for an additional 56% of the tests, as opposed to just guessing. Additionally, we simulate the scenario of a determined attacker placing himself inside the victim's social circle by employing dummy accounts. In this case, the accuracy of our attack greatly increases and reaches 100% when 120 faces per friend are accessible by the attacker, even though it is very accurate with as little as 10 faces.