Miracle-dz/UniFAR-FTUs huggingface dataset:
Methylxanthine Composition and Consumption Patterns of Cocoa and Chocolate Products

: This chapter has compiled and evaluated the current information on the methylxanthine composition of cocoa and various chocolate foods and beverages, as well as the consumption pattern for these commodities. Although the earliest recorded reference to cacao was in 1502, it was not until 1876 that milk chocolate was invented, an event that formed the backbone of the chocolate industry today. The consumption of cocoa throughout the world has been influenced by a number of factors, and the period of peak consumption occurred during the early to mid-1960s when these factors were highly favorable. The greatest consumption of cocoa in metric tons over the past 10 yr has been in the United States, although the highest per capita consumer during this period was Switzerland. The African continent has been historically the primary producer of raw cocoa, with the Ivory Coast currently being the largest individual supplier. Limited marketing survey data is available for the consumption of methylxanthines in chocolate foods and beverages. In children and teenagers, the major dietary source of caffeine was found to be tea, followed by soft drinks and coffee, respectively. Although chocolate foods and beverages ranked the lowest of these dietary sources to provide caffeine, they do constitute the major source of dietary theobromine. Cacao is the major natural source of the xanthine base theobromine. Small amounts of caffeine are present in the bean along with trace amounts of theophylline. The methylxanthine content of beans varies with the varietal type, and is influenced by the fermentation process. Chocolate liquor is a semifinished product commonly called "baking" or "cooking" chocolate. The average theobromine and caffeine content of liquors has been reported at 1.2% and 0.21%, respectively. Cocoa powder, which is prepared after removal of the cocoa butter, contains about 1.9% theobromine and 0.21% caffeine. Chocolate beverages comprise the most widely studied category of chocolate products. Hot cocoa provides 62 mg/serving of theobromine and 4 mg/serving of caffeine when prepared from commercial instant mixes. Instant cold chocolate milk mixes supply an average of 58 mg/serving of theobromine and 5 mg/serving of caffeine. The methylxanthine content of chocolate foods has received only slight attention in the literature. The methylxanthine content of sweet chocolate ranges from 0.359 to 0.628% for theobromine and 0.017 to 0.125% for caffeine. (ABSTRACT TRUNCATED AT 400 WORDS)
Mass spectrometry‐based methods for robust measurement of Alzheimer's disease biomarkers in biological fluids

Alzheimer's disease (AD) is the most common form of dementia affecting 60%–70% of people afflicted with this disease. Accurate antemortem diagnosis is urgently needed for early detection of AD to enable reliable estimation of prognosis, intervention, and monitoring of the disease. The National Institute on Aging/Alzheimer's Association sponsored the ‘Research Framework: towards a biological definition of AD’, which recommends using different biomarkers in living persons for a biomarker‐based definition of AD regardless of clinical status. Fluid biomarkers represent one of key groups of them. Since cerebrospinal fluid (CSF) is in direct contact with brain and many proteins present in the brain can be detected in CSF, this fluid has been regarded as the best biofluid in which to measure AD biomarkers. Recently, technological advancements in protein detection made possible the effective study of plasma AD biomarkers despite their significantly lower concentrations versus to that in CSF. This and other challenges that face plasma‐based biomarker measurements can be overcome by using mass spectrometry. In this review, we discuss AD biomarkers which can be reliably measured in CSF and plasma using targeted mass spectrometry coupled to liquid chromatography (LC/MS/MS). We describe progress in LC/MS/MS methods’ development, emphasize the challenges, and summarize major findings. We also highlight the role of mass spectrometry and progress made in the process of global standardization of the measurement of Aβ42/Aβ40. Finally, we briefly describe exploratory proteomics which seek to identify new biomarkers that can contribute to detection of co‐pathological processes that are common in sporadic AD.
A glance of the layered transition metal oxide cathodes in sodium and lithium-ion batteries: difference and similarities

The fast-growing demand for energy storage devices has prompted diverse battery techniques, while the state-of-the-art Li-ion batteries (LIBs) continue to flourish, Na-ion batteries (SIBs) have been identified to be a promising alternative to share the burden with LIBs, particularly for large-scale grid storage applications. Both LIBs and SIBs techniques work based on similar fundamental mechanisms, with a heavy focus on the intercalation chemistry of layered transition metal oxides. However, the differences between Li-ion and Na-ion in terms of their size and Lewis acidity induce many different behaviors when crystallizing or diffusing in layered cathode materials. This minireview summarizes some typical cases where Li and Na-ion differ in layered cathode materials and discusses potential approaches to leverage their similarities and dissimilarities for future developments of high-performance SIBs.
Nuclear speckles: dynamic hubs of gene expression regulation

Complex, multistep biochemical reactions that routinely take place in our cells require high concentrations of enzymes, substrates, and other structural components to proceed efficiently and typically require chemical environments that can inhibit other reactions in their immediate vicinity. Eukaryotic cells solve these problems by restricting such reactions into diffusion‐restricted compartments within the cell called organelles that can be separated from their environment by a lipid membrane, or into membrane‐less compartments that form through liquid–liquid phase separation (LLPS). One of the most easily noticeable and the earliest discovered organelle is the nucleus, which harbors the genetic material in cells where transcription by RNA polymerases produces most of the messenger RNAs and a plethora of noncoding RNAs, which in turn are required for translation of mRNAs in the cytoplasm. The interior of the nucleus is not a uniform soup of biomolecules and rather consists of a variety of membrane‐less bodies, such as the nucleolus, nuclear speckles (NS), paraspeckles, Cajal bodies, histone locus bodies, and more. In this review, we will focus on NS with an emphasis on recent developments including our own findings about the formation of NS by two large IDR‐rich proteins SON and SRRM2.
Hidden link in gut–joint axis: gut microbes promote rheumatoid arthritis at early stage by enhancing ascorbate degradation

With great interest, we read the review article by Agus et al, which suggested that gut microbiome alterations could affect metabolic homeostasis. Moreover, gut microbiome alterations in concert with metabolites perturbation could contribute to the early development of rheumatoid arthritis (RA). We thus conducted a threepronged association study on multiomics datasets to detect the potential microbiome– metabolites–arthritis link. We integrated multiomics datasets including gut metagenomics, clinical phenotypes and metabolites of blood and kneejoint synovial fluid from 122 participants in the healthy group (n=27), osteoarthritis (OA) group (n=19) and RA group (n=76), using a threepronged association framework (figure 1, online supplemental material). Metagenomic genes were collapsed into metagenomic species (MGS) 4 and grouped into KEGG functional modules (figure 1A). Additionally, the coabundant metabolites were categorised into metabolite clusters using WGCNA framework (figure 1A). The functional modules associated with clinical phenotypes (eg, types of arthritis and levels of cytokines) were further identified and the crossdomain associations between these modules and metabolite clusters were assessed (figure 1B). Furthermore, the leaveoneout analysis was performed to determine the MGS that particularly contributed to the observed linkage between functional modules and clinical phenotypes (figure 1C). We found that gut microbial functionality in ascorbate degradation (KEGG module: M00550) was positively correlated with the types of arthritis (healthy=0, OA=1, RA=2, pWilcox=2.15×10 ) and the levels of proinflammatory cytokines TNF-α (tumour necrosis factor-α, pWilcox=6.59×10 ) and IL-6 (interleukin-6, pWilcox=1.12×10 ). Ascorbate (vitamin C) was previously reported to prevent the development of inflammatory arthritis, possibly through facilitating collagen synthesis, moderating autoimmune responses and ameliorating inflammation. Additionally, the patients with RA are usually ascorbate deficient and require highdose supplementation to maintain an acceptable plasma level of ascorbate. In this study, the functional module of ascorbate degradation was observed to positively correlate with the blood metabolite cluster MB02 (pWilcox=6.90×10 ), which was represented by the level of palmitic acid (kME (eigengenebased connectivity) =0.911, kIN (intramodular connectivity) =3.46, online supplemental table 1) that acts as a proinflammatory factor, upregulating IL-6 secretion by human chondrocytes and fibroblastlike synovial cells in inflammatory arthritis. Furthermore, we found that Letter
The effect of self-referential processing on anxiety in response to naturalistic and laboratory stressors

ABSTRACT Although stressful life events increase risk for symptoms of Generalised Anxiety Disorder (GAD), we know little about mechanisms that increase GAD symptoms during times of stress. Despite evidence that self-referential processing contributes to other forms of psychopathology, namely depression, it is unknown whether self-referential processing also contributes to symptoms of GAD. Thus, we examined the association of self-referential processing with GAD symptoms in response to a naturalistic stressor (Study 1; n=135) and with anxiety-tension in response to a laboratory stressor (Study 2; n=56). In Study 1, participants completed the self-referential encoding task (SRET) in their initial weeks of university, and we assessed GAD symptoms four times across the semester. In Study 2, participants completed the SRET immediately before a laboratory stressor, and we assessed moment-to-moment changes in anxiety-tension. Greater negatively biased self-referential processing was associated with higher GAD symptoms at the start of university and greater reactivity to the laboratory stressor. In contrast, greater positively biased self-referential processing served as a protective factor associated with greater decline in symptoms over time. This study is the first to demonstrate that there are valence-specific effects of self-referential processing on anxiety, suggesting that self-referential processing may be relevant to GAD.
The Social Life of Viruses.

Despite their simplicity, viruses exhibit certain types of social interactions. Situations in which a given virus achieves higher fitness in combination with other members of the viral population have been described at the level of transmission, replication, suppression of host immune responses, and host killing, enabling the evolution of viral cooperation. Although cellular coinfection with multiple viral particles is the typical playground for these interactions, cooperation between viruses infecting different cells is also established through cellular and viral-encoded communication systems. In general, the stability of cooperation is compromised by cheater genotypes, as best exemplified by defective interfering particles. As predicted by social evolution theory, cheater invasion can be avoided when cooperators interact preferentially with other cooperators, a situation that is promoted in spatially structured populations. Processes such as transmission bottlenecks, organ compartmentalization, localized spread of infection foci, superinfection exclusion, and even discrete intracellular replication centers promote multilevel spatial structuring in viruses. Expected final online publication date for the Annual Review of Virology, Volume 8 is September 2021. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
First World Consensus Conference on pancreas transplantation: Part II – recommendations

The First World Consensus Conference on Pancreas Transplantation provided 49 jury deliberations regarding the impact of pancreas transplantation on the treatment of diabetic patients, and 110 experts’ recommendations for the practice of pancreas transplantation. The main message from this consensus conference is that both simultaneous pancreas‐kidney transplantation (SPK) and pancreas transplantation alone can improve long‐term patient survival, and all types of pancreas transplantation dramatically improve the quality of life of recipients. Pancreas transplantation may also improve the course of chronic complications of diabetes, depending on their severity. Therefore, the advantages of pancreas transplantation appear to clearly surpass potential disadvantages. Pancreas after kidney transplantation increases the risk of mortality only in the early period after transplantation, but is associated with improved life expectancy thereafter. Additionally, preemptive SPK, when compared to SPK performed in patients undergoing dialysis, appears to be associated with improved outcomes. Time on dialysis has negative prognostic implications in SPK recipients. Increased long‐term survival, improvement in the course of diabetic complications, and amelioration of quality of life justify preferential allocation of kidney grafts to SPK recipients. Audience discussions and live voting are available online at the following URL address: http://mediaeventi.unipi. it/category/1st‐world‐consensus‐conference‐of‐pancreas‐transplantation/246.
Candidalysin delivery to the invasion pocket is critical for host epithelial damage induced by Candida albicans

The human pathogenic fungus Candida albicans is a frequent cause of mucosal infections. Although the ability to transition from the yeast to the hypha morphology is essential for virulence, hypha formation and host cell invasion per se are not sufficient for the induction of epithelial damage. Rather, the hypha‐associated peptide toxin, candidalysin, a product of the Ece1 polyprotein, is the critical damaging factor. While synthetic, exogenously added candidalysin is sufficient to damage epithelial cells, the level of damage does not reach the same level as invading C. albicans hyphae. Therefore, we hypothesized that a combination of fungal attributes is required to deliver candidalysin to the invasion pocket to enable the full damaging potential of C. albicans during infection. Utilising a panel of C. albicans mutants with known virulence defects, we demonstrate that the full damage potential of C. albicans requires the coordinated delivery of candidalysin to the invasion pocket. This process requires appropriate epithelial adhesion, hyphal extension and invasion, high levels of ECE1 transcription, proper Ece1 processing and secretion of candidalysin. To confirm candidalysin delivery, we generated camelid VHHs (nanobodies) specific for candidalysin and demonstrate localization and accumulation of the toxin only in C. albicans‐induced invasion pockets. In summary, a defined combination of virulence attributes and cellular processes is critical for delivering candidalysin to the invasion pocket to enable the full damage potential of C. albicans during mucosal infection.
Nitrogen and phosphorus losses by surface runoff and soil microbial communities in a paddy field with different irrigation and fertilization managements

Rice cultivation usually involves high water and fertilizer application rates leading to the nonpoint pollution of surface waters with phosphorus (P) and nitrogen (N). Here, a 10-year field experiment was conducted to investigate N and P losses and their impact factors under different irrigation and fertilization regimes. Results indicated that T2 (Chemical fertilizer of 240 kg N ha−1, 52 kg P ha−1, and 198 kg K ha−1 combined with shallow intermittent irrigation) decreased N loss by 48.9% compared with T1 (Chemical fertilizer of 273 kg N ha−1, 59 kg P ha−1, and 112 kg K ha−1 combined with traditional flooding irrigation). The loss ratio (total N loss loading/amount of applied N) of N was 9.24–15.90%, whereas that of P was 1.13–1.31% in all treatments. Nitrate N (NO3-−N) loss was the major proportion accounting for 88.30–90.65% of dissolved inorganic N loss through surface runoff. Moreover, the N runoff loss was mainly due to high fertilizer input, soil NO3-−N, and ammonium N (NH4+−N) contents. In addition, the N loss was accelerated by Bacteroidetes, Proteobacteria, Planotomycetes, Nitrospirae, Firmicutes bacteria and Ascomycota fungi, but decreased by Chytridiomycota fungi whose contribution to the N transformation process. Furthermore, T2 increased agronomic N use efficiency (AEN) and rice yield by 32.81% and 7.36%, respectively, in comparison with T1. These findings demonstrated that T2 might be an effective approach to ameliorate soil chemical properties, regulate microbial community structure, increase AEN and consequently reduce N losses as well as maintaining rice yields in the present study.
An unusual cause of acute cholangitis

Endoscopic treatment can be challenging in patients presenting with biliary adverse events and a biliodigestive diversion. Multiples approaches have been described. In the past decade, an overall technical success of 80–86% [1–3] of enteroscopy-assisted endoscopic retrograde cholangiopancreatography (ERCP) has been described. Herein, we report the original case of a 65-year-old patient with sickle cell disease who was referred to our department for an unusual acute cholangitis. The patient had undergone biliodigestive anastomosis and Roux-en-Y jejunal loop 25 years ago because of refractory macrolithiasis of the common bile duct. Of note, patients with sickle cell disease are prone to developing biliary adverse events [4]. The patient presented with fever and jaundice. The abdominal computed tomography (CT) scan confirmed the dilatation of the whole biliary tract and revealed a contiguous dilatation of the jejunal loop upstream of an impacted stone of 30mm (▶Fig. 1). Once the absence of another cause of biliary obstruction was confirmed by magnetic resonance cholangiopancreatography (MRCP) [5], hybrid enteroscopy-assisted ERCP was proposed for the patient. The enteroscopy was performed under general anesthesia, using a 3.2-mm working channel double-balloon enteroscope (EN-580T, Fujifilm, Tokyo, Japan). The push-and-pull technique was used to progress through the small bowel and the biliary loop was easily catheterized. Approximately 40 cm beyond the anastomosis, we identified a large biliary stone completely obstructing the lumen, impacted on a relative stenosis (▶Fig. 2). Lithotripsy was performed using 30-mm braided snare (Lariat; Life Partners Europe, Bagnolet, France) (▶Video 1). After multiple passes, the stone was completely broken up and the obstruction eliminated. The patient recovered well and was discharged 3 days later. The abdominal CTscan performed 1month later confirmed the absence of residual stones.
The role of race and scientific trust on support for COVID-19 social distancing measures in the United States

Pundits and academics across disciplines note that the human toll brought forth by the novel coronavirus (COVID-19) pandemic in the United States (U.S.) is fundamentally unequal for communities of color. Standing literature on public health posits that one of the chief predictors of racial disparity in health outcomes is a lack of institutional trust among minority communities. Furthermore, in our own county-level analysis from the U.S., we find that counties with higher percentages of Black and Hispanic residents have had vastly higher cumulative deaths from COVID-19. In light of this standing literature and our own analysis, it is critical to better understand how to mitigate or prevent these unequal outcomes for any future pandemic or public health emergency. Therefore, we assess the claim that raising institutional trust, primarily scientific trust, is key to mitigating these racial inequities. Leveraging a new, pre-pandemic measure of scientific trust, we find that trust in science, unlike trust in politicians or the media, significantly raises support for COVID-19 social distancing policies across racial lines. Our findings suggest that increasing scientific trust is essential to garnering support for public health policies that lessen the severity of the current, and potentially a future, pandemic.
Predicting road quality using high resolution satellite imagery: A transfer learning approach

Recognizing the importance of road infrastructure to promote human health and economic development, actors around the globe are regularly investing in both new roads and road improvements. However, in many contexts there is a sparsity—or complete lack—of accurate information regarding existing road infrastructure, challenging the effective identification of where investments should be made. Previous literature has focused on overcoming this gap through the use of satellite imagery to detect and map roads. In this piece, we extend this literature by leveraging satellite imagery to estimate road quality and concomitant information about travel speed. We adopt a transfer learning approach in which a convolutional neural network architecture is first trained on data collected in the United States (where data is readily available), and then “fine-tuned” on an independent, smaller dataset collected from Nigeria. We test and compare eight different convolutional neural network architectures using a dataset of 53,686 images of 2,400 kilometers of roads in the United States, in which each road segment is measured as “low”, “middle”, or “high” quality using an open, cellphone-based measuring platform. Using satellite imagery to estimate these classes, we achieve an accuracy of 80.0%, with 99.4% of predictions falling within the actual or an adjacent class. The highest performing base model was applied to a preliminary case study in Nigeria, using a dataset of 1,000 images of paved and unpaved roads. By tailoring our US-model on the basis of this Nigeria-specific data, we were able to achieve an accuracy of 94.0% in predicting the quality of Nigerian roads. A continuous case estimate also showed the ability, on average, to predict road quality to within 0.32 on a 0 to 3 scale (with higher values indicating higher levels of quality).