bluuebunny/crossref_metadata_2025 huggingface dataset:
Celnica na granicy imperium – Muzeum św. Brata Alberta w Igołomi / Customs house on the border of the empire. The Museum of St. Brother Albert in Igołomia
Authors: Siwek Andrzej
Published: November 2020

In 1815, Igołomia became a border village. The authorities of the Kingdom of Poland, and then the tsarist administration maintained a customs house in the village. Its role was to facilitate the trade of goods from the territory of the Kraków Republic and the Austrian partition to the Russian partition. In 1844–1846 Wojciech Chmielowski, father of Adam, the future Saint Brother Albert, was the head of the 1st-class customs house in Igołomia. Adam was born here on August 20, 1845. His short time in Igołomia did not affect his fate, but the historical place of his birth was commemorated. When the Albertine Sisters began their service in Igołomia in 1986, this memory was strengthened. In 1994–1995 a new religious house and the Museum of St. Brother Albert were founded. The museum was located in the historic customs building, although the building itself was not the home where the Saint was born. This building was subjected to demolition after the mid-19th century. In its place after 1857, a new customs house was built, which survived until recently, when it was demolished in 2010 and a new museum building was erected in its place. The museum refers to the place of birth of Saint Brother Albert, and part of the exhibition displays the tradition of the customs house.
Wielka Wojna na nadwiślańskim przedpolu Twierdzy Kraków / The Great War on the Vistula River outskirts of the Kraków Fortress
Authors: Niebylski Jakub
Published: November 2020

The study presents a description of the theatre of war operations on the left bank of theVistula River, on the eastern foreground of the Austro-Hungarian Kraków Fortress during the Great War, later called World War I. The fighting took place in the area of the former Russian partition, on November 16–25, 1914 and December 2–6, 1914. They were fought in the area occupied from August 6, 1914 by Austria-Hungary after the declaration of war on Russia. In historiography, these fights are called the Battle of Kraków. It was aimed at stopping the Russian offensive heading west and preventing the capture of the Kraków Fortress and stopping the further march of Russian army on Silesia, Bohemia and Berlin. The result of these actions was the military success of the Austro-Hungarian army, breaking the front and pushing the Russian troops eastwards, paid for with great personal losses on both sides and the destruction of local infrastructure. The testimonies of these events are war graves and cemeteries located in the battlefields, as well as numerous finds – remains of battles.
Lotnisko Pobiednik 1939 / Airstrip in Pobiednik 1939
Authors: Włodarczak Piotr
Published: November 2020

In the interwar period, in the northern part of the village of Pobiednik Wielki in today’s district of Kraków, a backup landing pad of the 2nd Aviation Regiment was built, based at Rakowice-Czyżyny airport in Kraków. From 1 to 4 September 1939, various air units of this regiment were stationed in Pobiednik – two squadrons of the Cracow III/2 Fighter Squadron (Nos 121 and 122), as well as planes of the 23rd and 26th Observation Squadron and Liaison Platoon No. 3. Fighter aircraft took off from here to fight German air bomber raids, and reconnaissance planes worked for the land units of the „Kraków” Army. The stay at the airstrip in Pobiednik, lasting only a few dozen hours, was an intensely active time for the Kraków aviation units.
Provincial mycology and the legacy of Henry Thomas Soppitt (1858–1899) (W. T. Stearn Prize 2019)
Authors: Smith Nathan E. C.
Published: November 2020

The essay explores the life and legacy of Henry Thomas Soppitt, focusing on his elucidation of the life cycle of the rust fungus Puccinia bistortae (F. Strauss) DC. It focuses on the impact this discovery had on the Yorkshire mycological community during a period of threat to its standing caused by the professionalization of science and subsequent degradation of the amateur. It goes on to explores how two Yorkshire mycologists and participants in the discovery, Charles Crossland and James Needham, used accounts of Soppitt's discovery to ensure his legacy and, later, to attempt to ensure the legacy of their community. It shows how these accounts were varied in their content and medium and analyses the relative value of collections to printed text to Yorkshire mycologists through the differences in their accounts.
Aloïs Humbert (1829–1887), the first professional curator of natural history in Geneva
Authors: Hollier John , Hollier Anita
Published: November 2020

Aloïs Humbert was the first scientist employed by the Musée académique de Genève, but his career as a whole has a much closer resemblance to his “gentleman scientist” contemporaries such as Henri de Saussure and Alphonse Pictet (both of whom also studied under François-Jules Pictet and contributed to the development of the museum) than to that of his successor in the post, Godefroy Lunel. His career is presented to throw light on the professionalization of science in nineteenth-century Geneva, and it is suggested that his prestige raised the status of the role of museum scientist, to the benefit of his successors.
The limits of imperial influence: John James Audubon in British North America
Authors: Lindsay Debra J.
Published: November 2020

For two decades, John James Audubon (1785–1851) travelled widely and frequently while working on his illustrated natural history volumes – still highly prized today for their aesthetic and scientific merit: Birds of America (1827–1838) and Viviparous Quadrupeds of North America (1846–1854). Neither independently wealthy nor employed as a salaried scientist, the artist-naturalist with a flair for marketing financed his projects by selling subscriptions. Successfully marketing Birds to members of the British aristocracy, as well as to organizations and to artistic and intellectual elites, Audubon was reluctant to take Quadrupeds to Britain even though sales there were key to the financial viability of his work. Instead, in 1842 Audubon travelled to Canada (now Ontario and Quebec), the most populous region of British North America. The colony was, he calculated, a viable source of subscribers; however, he was wrong. Moreover, having travelled to British North America previously, he should have expected modest returns. Nonetheless, he was optimistic that this expedition would succeed where those to New Brunswick (1832) and Labrador and Newfoundland (1833) had failed. This paper examines why success eluded Audubon in the colonies, arguing that entrepreneurialism buttressed by patronage – a winning strategy in Britain – failed because there was a vast difference between metropolis and hinterland when it came to supporting the arts and sciences.
Great auk (Pinguinus impennis) eggs in Bonn: correspondence between Emile Parzudaki and Robert Champley
Authors: Töpfer Till
Published: November 2020

Although Charles and Emile Parzudaki were well-connected natural history dealers of nineteenth-century Paris, many aspects of their life and work remain unknown. The example of two letters from Emile Parzudaki to Robert Champley that accompanied three great auk ( Pinguinus impennis) eggs to the Zoologisches Forschungsmuseum Alexander Koenig in Bonn reveal new aspects of the Parzudaki enterprise, indicating at least some travelling and collecting activities of Charles Parzudaki beyond Europe.
Frederick William Flattely (1888–1937): naturalist and “Renaissance man”
Authors: Moore P. Geoffrey
Published: November 2020

Attention is drawn to the contributions of Frederick William Flattely (1888–1937), noting the wide range of his natural history publications. He is best known for his ground-breaking guidebook on shore ecology, The Biology of the Sea-shore, first published with Charles Walton in 1922. Both started their careers at University College of Wales, Aberystwyth. Flattely was greatly influenced there by Professor Herbert J. Fleure; hence his interest in environmental matters, agriculture and parasitology. After removing via the University of Aberdeen to the University of Durham and concentrating on marine issues, he moved thence to the League of Nations in Rome as a technical editor (using his extensive linguistic skills). Of German extraction, he changed his surname from Durlacher to Flattely in 1914. He eventually took-up a position teaching biology at Leighton Park School, Reading. He is remembered there as an excellent teacher and motivator of students.
Narrative histories in mycology and the legacy of George Edward Massee (1845–1917)
Authors: Smith Nathan E. C.
Published: November 2020

Mycology is a relatively small and young discipline that has yet to achieve the institutional presence of similar disciplines such as botany and zoology. Because of this, mycological histories are often written by practitioners aiming to establish a narrative of professionalization that confirms mycology as a scientific discipline instead of a natural history pursuit. George Edward Massee (1845–1917) was one of the foremost mycologists of the late nineteenth century, achieving the top position in the field as Principal Assistant (Cryptogams) at the Royal Botanic Gardens, Kew, and publishing over 250 books and articles. Providing a link between the great Victorian mycologists Mordecai Cubitt Cooke (1825–1914) and the Revd Miles Joseph Berkeley (1803–1889) and the more modern school that included the likes of Elsie Maud Wakefield (1886–1972), he achieved this position without a university education. However, since his death, his achievements have been subject to multiple negative assessments and, as a result, he has become increasingly obscured in the history of British mycology. The majority of these unfavourable appraisals originated from the publications of Dr John Ramsbottom (1885–1974), a mycologist and historian who was a key member of the British Mycological Society and a founding member of the Society for the Bibliography of Natural History. These articles were published across the first half of the twentieth century, and Ramsbottom's works have since become standard texts in both the biography of Massee and the history of British mycology. Here I question the validity of the substance of Ramsbottom's claims against Massee, given the circumstances under which Ramsbottom's articles were written and the relationship between Massee and the fledgling British Mycological Society, initially run by Carleton Rea (1861–1946) and of which Ramsbottom was a senior member. I examine wider reasons for such strong criticism of Massee and explore the professional differences and relationships between Massee and Ramsbottom, placing the analysis firmly in the context of changing scientific practice occurring in the early twentieth century.
Post-World War II Group Psychology and the Limits of Leadership: Bion, Lacan and the Leaderless Goup
Authors: Maher Max
Published: November 2020

This article attempts to reveal something different about the afterlife of a number of innovations made in British psychiatry during World War II – in particular around the notion of leadership – by reading them in a much broader context which includes Jacques Lacan's article ‘Logical Time and the Assertion of Anticipated Certainty’ (1945). Within such a broader trajectory, considerations of leaders and leaderlessness, which pressed towards democracy and egalitarianism, intersect (paradoxically) with other currents, equally radical, which envision a totalizing reduction of individuals to a technocratic mass. The article's starting point is Jacques Lacan's high praise of British military psychiatry – in particular of W.H. Bion, John Rickman and John Rawlings Rees, consulting psychiatrist to the army during the war. It then weighs Lacan's description of their achievements against a historical account of where such experiments led in the post-war context, and the social functions envisaged for them, that differed from those Lacan hoped they could perform. It concludes with a comparison of Lacan's article ‘Logical Time’, his first published after reading Bion and Rickman, to the contemporary work of Friedrich von Hayek, the early theorist of neoliberal economics, to illustrate the profound ambiguity which exists within the political implications of psychoanalytic theories of groups.
Pandemics and Political Development: The Electoral Legacy of the Black Death in Germany
Authors: Gingerich Daniel , Vogler Jan
Published: November 2020

Do pandemics have lasting consequences for political behavior? We examine the consequences of the most deadly pandemic in recorded history: the Black Death (1347-1351). Our claim is that pandemics can influence politics in the long run if they impose sufficient loss of life so as to augment the price of labor relative to other factors of production. When this occurs, labor repressive regimes become untenable, which ultimately leads to the development of proto-democratic institutions and associated political cultures that shape modalities of political engagement for generations. We test our theory by tracing out the Black Death’s consequences in German-speaking Central Europe. We find that areas hit hardest by the pandemic were more likely to:(1) adopt inclusive political institutions and equitable land ownership patterns;(2) exhibit electoral behavior indicating independence from landed elite influence during the transition to mass politics; and (3) have significantly lower vote shares for Hitler's National Socialist Party.
A Machine Learning Approach for Tracing Tumor Original Sites With Gene Expression Profiles
Authors: Liang Xin , Zhu Wen , Liao Bo , Wang Bo , Yang Jialiang , Mo Xiaofei , Li Ruixi
Published: November 2020

Some carcinomas show that one or more metastatic sites appear with unknown origins. The identification of primary or metastatic tumor tissues is crucial for physicians to develop precise treatment plans for patients. With unknown primary origin sites, it is challenging to design specific plans for patients. Usually, those patients receive broad-spectrum chemotherapy, while still having poor prognosis though. Machine learning has been widely used and already achieved significant advantages in clinical practices. In this study, we classify and predict a large number of tumor samples with uncertain origins by applying the random forest and Naive Bayesian algorithms. We use the precision, recall, and other measurements to evaluate the performance of our approach. The results have showed that the prediction accuracy of this method was 90.4 for 7,713 samples. The accuracy was 80% for 20 metastatic tumors samples. In addition, the 10-fold cross-validation is used to evaluate the accuracy of classification, which reaches 91%.
Antibiotics as Major Disruptors of Gut Microbiota
Authors: Ramirez Jaime , Guarner Francisco , Bustos Fernandez Luis , Maruy Aldo , Sdepanian Vera Lucia , Cohen Henry
Published: November 2020

Advances in culture-independent research techniques have led to an increased understanding of the gut microbiota and the role it plays in health and disease. The intestine is populated by a complex microbial community that is organized around a network of metabolic interdependencies. It is now understood that the gut microbiota is vital for normal development and functioning of the human body, especially for the priming and maturation of the adaptive immune system. Antibiotic use can have several negative effects on the gut microbiota, including reduced species diversity, altered metabolic activity, and the selection of antibiotic-resistant organisms, which in turn can lead to antibiotic-associated diarrhea and recurrent Clostridioides difficile infections. There is also evidence that early childhood exposure to antibiotics can lead to several gastrointestinal, immunologic, and neurocognitive conditions. The increase in the use of antibiotics in recent years suggests that these problems are likely to become more acute or more prevalent in the future. Continued research into the structure and function of the gut microbiota is required to address this challenge.
Parasocial Relationships With President Trump as a Predictor of COVID-19 Information Seeking
Authors: Kelly Stephanie , Goke Ryan , McCall Mackenzy , Dowell S. Greg
Published: November 2020

As the number of COVID-19 cases climbed in the United States, President Trump came under fire for dismissing its severity despite evidence to the contrary. Those most impressionable by the President's claims might be those who have established a parasocial relationship with him. Results of this survey study indicate that each of the three parasocial variables assessed (i.e., friends, understanding, and brand), were negatively related to information seeking for COVID-19. Moreover, initial evidence was found that identification with the Trump brand was an indirect influence of information seeking. Consistent with the supported model, women and Democrats reported higher information seeking for COVID-19 than men and other political groups.
Technology and Media Use in Preschool Classrooms: Prevalence, Purposes, and Contexts
Authors: Dore Rebecca A. , Dynia Jaclyn M.
Published: November 2020

Although the amount of time that preschoolers spend with screen media at home is continuing to increase, less is known about the types of media experiences children are having in preschool settings. Furthermore, little research has investigated the purposes for which preschool teachers use technology and media in the classroom and the contexts in which such use occurs. The current study addresses that gap by providing a nuanced picture of technology and media use in preschool classrooms. Lead teachers were recruited via email lists of educators who participated in previous studies or expressed interest in receiving communication from our research group. Participants (N = 312, 98.6% female; Mage = 43.9 years) all taught preschool-age children. Participants were first asked to check which of four devices they used with children in their classroom (tablet, smartphone, computer, television). If participants responded that they used each device, they were asked how often. Survey items also assessed (1) Purposes: how often teachers used each device for instructional purposes (e.g., teaching new material, practicing material) and non-instructional purposes (e.g., entertainment, as a reward), and (2) Context: how often teachers used devices for both teacher-supported and non-teacher-supported activities. Results indicated that tablet and computer use were most common, whereas smartphone and television use were less prevalent. Teachers reported most frequently using tablets, computers, and smartphones for instructional purposes. Television was most frequently used for entertainment. Tablets and smartphones were most frequently used in teacher-supported individual contexts, whereas computers were most frequently used in teacher-supported whole group contexts. Latent class analysis showed five classes of classroom technology and media use: tablet and computer users, tablet only users, low technology users, computer for teacher-supported instruction users, and television only users. Finally, we determined that these classes were predicted by program funding (publicly- or privately-funded), teacher experience, and teacher education.
The VHL/HIF Axis in the Development and Treatment of Pheochromocytoma/Paraganglioma
Authors: Peng Song , Zhang Jun , Tan Xintao , Huang Yiqiang , Xu Jing , Silk Natalie , Zhang Dianzheng , Liu Qiuli , Jiang Jun
Published: November 2020

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors originating from chromaffin cells in the adrenal medulla (PCCs) or extra-adrenal sympathetic or parasympathetic paraganglia (PGLs). About 40% of PPGLs result from germline mutations and therefore they are highly inheritable. Although dysfunction of any one of a panel of more than 20 genes can lead to PPGLs, mutations in genes involved in the VHL/HIF axis includingPHD,VHL,HIF-2A (EPAS1), andSDHxare more frequently found in PPGLs. Multiple lines of evidence indicate that pseudohypoxia plays a crucial role in the tumorigenesis of PPGLs, and therefore PPGLs are also known as metabolic diseases. However, the interplay between VHL/HIF-mediated pseudohypoxia and metabolic disorder in PPGLs cells is not well-defined. In this review, we will first discuss the VHL/HIF axis and genetic alterations in this axis. Then, we will dissect the underlying mechanisms in VHL/HIF axis-driven PPGL pathogenesis, with special attention paid to the interplay between the VHL/HIF axis and cancer cell metabolism. Finally, we will summarize the currently available compounds/drugs targeting this axis which could be potentially used as PPGLs treatment, as well as their underlying pharmacological mechanisms. The overall goal of this review is to better understand the role of VHL/HIF axis in PPGLs development, to establish more accurate tools in PPGLs diagnosis, and to pave the road toward efficacious therapeutics against metastatic PPGLs.
A Deep Learning Approach to Population Structure Inference in Inbred Lines of Maize
Authors: López-Cortés Xaviera Alejandra , Matamala Felipe , Maldonado Carlos , Mora-Poblete Freddy , Scapim Carlos Alberto
Published: November 2020

Analysis of population genetic variation and structure is a common practice for genome-wide studies, including association mapping, ecology, and evolution studies in several crop species. In this study, machine learning (ML) clustering methods, K-means (KM), and hierarchical clustering (HC), in combination with non-linear and linear dimensionality reduction techniques, deep autoencoder (DeepAE) and principal component analysis (PCA), were used to infer population structure and individual assignment of maize inbred lines, i.e., dent field corn (n= 97) and popcorn (n= 86). The results revealed that the HC method in combination with DeepAE-based data preprocessing (DeepAE-HC) was the most effective method to assign individuals to clusters (with 96% of correct individual assignments), whereas DeepAE-KM, PCA-HC, and PCA-KM were assigned correctly 92, 89, and 81% of the lines, respectively. These findings were consistent with both Silhouette Coefficient (SC) and Davies–Bouldin validation indexes. Notably, DeepAE-HC also had better accuracy than the Bayesian clustering method implemented in InStruct. The results of this study showed that deep learning (DL)-based dimensional reduction combined with ML clustering methods is a useful tool to determine genetically differentiated groups and to assign individuals into subpopulations in genome-wide studies without having to consider previous genetic assumptions.
Immune Status Against Hepatitis B in Patients After Allogeneic Hematopoietic Cell Transplantation—Factors Affecting Early and Long-Lasting Maintenance of Protective Anti-HBs Titers
Authors: Piekarska Agnieszka , Wisniewski Piotr , Lewandowski Krzysztof , Gil Lidia , Trzonkowski Piotr , Bieniaszewska Maria , Zaucha Jan Maciej
Published: November 2020

The immunization of allogeneic hematopoietic cell transplantation (HCT) recipients against vaccine-preventable diseases is a part of posttransplantation guidelines. We conducted a prospective study to assess clinical and immunological parameters that would determine the response and long-term maintenance of protective antibody titers upon the hepatitis B virus (HBV) vaccination after HCT. The investigated variables included: vaccination of the HCT recipients and their donors prior to HCT, chronic graft versus host disease (cGVHD) and the timing of post-HCT vaccination, and B- and T-cell subtype status. Forty-two patients were immunized with three or more doses of recombinant hepatitis B surface antigen (rHBsAg) administered according to the individualized schedule of 0-1-2-6-(12) months. After vaccination, seroconversion was achieved in the whole group. The vaccines were categorized according to the antibody (Ab) titers as weak (WRs; 28.7%), good (GRs; 38%) or very good responders (VGRs; 3.3%). In multivariate logistic regression, severe cGVHD (OR= 15.5), and preceding donor immunization (OR= 0.13) were independent predictors of a weak response to vaccination. A prior belonging to the WR group impaired the durability of protection (OR= 0.17) at a median follow-up of 11.5 years. Patients with severe cGVHD showed a trend toward lower median Ab titers, although they required a higher rate of booster vaccine doses. All VGRs had CD4+ cells > 0.2 x 106/L. There was a lower mean rate of CD4+IL2+ lymphocytes in WRs. Vaccination demonstrated the immunomodulatory effect on B-cell and T-cell subsets and a Th1/Th2 cytokine profile, while shifts depended on a history of severe cGVHD and the type of vaccine responder. To conclude, vaccination of HCT donors against HBV allows a better response to vaccination in the respective HCT recipients. Double doses of rHBsAg should be considered in patients with cGVHD and in those not immunized before HCT. A dedicated intensified vaccination schedule should be administered to WRs.
A Neutrophil-Driven Inflammatory Signature Characterizes the Blood Transcriptome Fingerprint of Psoriasis
Authors: Rawat Arun , Rinchai Darawan , Toufiq Mohammed , Marr Alexandra K. , Kino Tomoshige , Garand Mathieu , Tatari-Calderone Zohreh , Kabeer Basirudeen Syed Ahamed , Krishnamoorthy Navaneethakrishnan , Bedognetti Davide , Karim Mohammed Yousuf , Sastry Konduru S. , Chaussabel Damien
Published: November 2020

Transcriptome profiling approaches have been widely used to investigate the mechanisms underlying psoriasis pathogenesis. Most researchers have measured changes in transcript abundance in skin biopsies; relatively few have examined transcriptome changes in the blood. Although less relevant to the study of psoriasis pathogenesis, blood transcriptome profiles can be readily compared across various diseases. Here, we used a pre-established set of 382 transcriptional modules as a common framework to compare changes in blood transcript abundance in two independent public psoriasis datasets. We then compared the resulting “transcriptional fingerprints” to those obtained for a reference set of 16 pathological or physiological states. The perturbations in blood transcript abundance in psoriasis were relatively subtle compared to the changes we observed in other autoimmune and auto-inflammatory diseases. However, we did observe a consistent pattern of changes for a set of modules associated with neutrophil activation and inflammation; interestingly, this pattern resembled that observed in patients with Kawasaki disease. This similarity between the blood-transcriptome signatures in psoriasis and Kawasaki disease suggests that the immune mechanisms driving their pathogenesis might be partially shared.
CD71+ Erythroid Cells in Human Neonates Exhibit Immunosuppressive Properties and Compromise Immune Response Against Systemic Infection in Neonatal Mice
Authors: Elahi Shokrollah , Vega-López Marco Antonio , Herman-Miguel Vladimir , Ramírez-Estudillo Carmen , Mancilla-Ramírez Javier , Motyka Bruce , West Lori , Oyegbami Olaide
Published: November 2020

Newborns are highly susceptible to infectious diseases. The underlying mechanism of neonatal infection susceptibility has generally been related to their under-developed immune system. Nevertheless, this notion has recently been challenged by the discovery of the physiological abundance of immunosuppressive erythroid precursors CD71+erythroid cells (CECs) in newborn mice and human cord blood. Here, as proof of concept, we show that these cells are also abundant in the peripheral blood of human newborns. Although their frequency appears to be more variable compared to their counterparts in mice, they rapidly decline by 4 weeks of age. However, their proportion remains significantly higher in infants up to six months of age compared to older infants. We found CD45 expressing CECs, as erythroid progenitors, were the prominent source of reactive oxygen species (ROS) production in both humans and mice. Interestingly, a higher proportion of CD45+CECs was observed in the spleen versus bone marrow of neonatal mice, which was associated with a higher ROS production by splenic CECs compared to their siblings in the bone marrow. CECs from human newborns suppressed cytokine production by CD14 monocytes and T cells, which was partially abrogated by apocynin in vitro. Moreover, the depletion of CECs in neonatal mice increased the number of activated effector immune cells in their spleen and liver, which rendered them more resistant to Listeria monocytogenes infection. This was evident by a significant reduction in the bacteria load in the spleen, liver and brain of treated-mice compared to the control group, which enhanced their survival rate. Our finding highlights the immunoregulatory processes mediated by CECs in newborns. Thus, such tightly regulated immune system in newborns/infants may explain one potential mechanism for the asymptomatic or mild COVID-19 infection in this population.
Vitamin D/CD46 Crosstalk in Human T Cells in Multiple Sclerosis
Authors: Killick Justin , Hay Joanne , Morandi Elena , Vermeren Sonja , Kari Saniya , Angles Thibault , Williams Anna , Damoiseaux Jan , Astier Anne L.
Published: November 2020

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS), in which T-cell migration into the CNS is key for pathogenesis. Patients with MS exhibit impaired regulatory T cell populations, and both Foxp3+ Tregs and type I regulatory T cells (Tr1) are dysfunctional. MS is a multifactorial disease and vitamin D deficiency is associated with disease. Herein, we examined the impact of 1,25(OH)2D3 on CD4+ T cells coactivated by either CD28 to induce polyclonal activation or by the complement regulator CD46 to promote Tr1 differentiation. Addition of 1,25(OH)2D3 led to a differential expression of adhesion molecules on CD28- and CD46-costimulated T cells isolated from both healthy donors or from patients with MS. 1,25(OH)2D3 favored Tr1 motility though a Vitamin D-CD46 crosstalk highlighted by increased VDR expression as well as increased CYP24A1 and miR-9 in CD46-costimulated T cells. Furthermore, analysis of CD46 expression on T cells from a cohort of patients with MS supplemented by vitamin D showed a negative correlation with the levels of circulating vitamin D. Moreover, t-Distributed Stochastic Neighbor Embedding (t-SNE) analysis allowed the visualization and identification of clusters increased by vitamin D supplementation, but not by placebo, that exhibited similar adhesion phenotype to what was observed in vitro. Overall, our data show a crosstalk between vitamin D and CD46 that allows a preferential effect of Vitamin D on Tr1 cells, providing novel key insights into the role of an important modifiable environmental factor in MS.
Integration of HF Radar Observations for an Enhanced Coastal Mean Dynamic Topography
Authors: Caballero Ainhoa , Mulet Sandrine , Ayoub Nadia , Manso-Narvarte Ivan , Davila Xabier , Boone Christine , Toublanc Florence , Rubio Anna
Published: November 2020

Satellite altimeters provide continuous information of the sea level variability and mesoscale processes for the global ocean. For estimating the sea level above the geoid and monitoring the full ocean dynamics from altimeters measurements, a key reference surface is needed: The Mean Dynamic Topography (MDT). However, in coastal areas, where, in situ measurements are sparse and the typical scales of the motion are generally smaller than in the deep ocean, the global MDT solutions are less accurate than in the open ocean, even if significant improvement has been done in the past years. An opportunity to fill in this gap has arisen with the growing availability of long time-series of high-resolution HF radar surface velocity measurements in some areas, such as the south-eastern Bay of Biscay. The prerequisite for the computation of a coastal MDT, using the newly available data of surface velocities, was to obtain a robust methodology to remove the ageostrophic signal from the HF radar measurements, in coherence with the scales resolved by the altimetry. To that end, we first filtered out the tidal and inertial motions, and then, we developed and tested a method that removed the Ekman component and the remaining divergent part of the flow. A regional high-resolution hindcast simulation was used to assess the method. Then, the processed HF radar geostrophic velocities were used in synergy with additional in situ data, altimetry, and gravimetry to compute a new coastal MDT, which shows significant improvement compared with the global MDT. This study showcases the benefit of combining satellite data with continuous, high-frequency, and synoptic in situ velocity data from coastal radar measurements; taking advantage of the different scales resolved by each of the measuring systems. The integrated analysis of in situ observations, satellite data, and numerical simulations has provided a further step in the understanding of the local ocean processes, and the new MDT a basis for more reliable monitoring of the study area. Recommendations for the replicability of the methodology in other coastal areas are also provided. Finally, the methods developed in this study and the more accurate regional MDT could benefit present and future high-resolution altimetric missions.
Crop-Zone Weed Mycobiomes of the South-Western Australian Grain Belt
Authors: Michael Pippa J. , Jones Darcy , White Nicole , Hane James K. , Bunce Michael , Gibberd Mark
Published: November 2020

In the absence of a primary crop host, secondary plant hosts may act as a reservoir for fungal plant pathogens of agricultural crops. Secondary hosts may potentially harbor heteroecious biotrophs (e.g., the stripe rust fungus Puccinia striiformis) or other pathogens with broad host ranges. Agricultural grain production tends toward monoculture or a limited number of crop hosts over large regions, and local weeds are a major source of potential secondary hosts. In this study, the fungal phyllospheres of 12 weed species common in the agricultural regions of Western Australia (WA) were compared through high-throughput DNA sequencing. Amplicons of D2 and ITS were sequenced on an Illumina MiSeq system using previously published primers and BLAST outputs analyzed using MEGAN. A heatmap of cumulative presence–absence for fungal taxa was generated, and variance patterns were investigated using principal components analysis (PCA) and canonical correspondence analysis (CCA). We observed the presence of several major international crop pathogens, including basidiomycete rusts of the Puccinia spp., and ascomycete phytopathogens of the Leptosphaeria and Pyrenophora genera. Unrelated to crop production, several endemic pathogen species including those infecting Eucalyptus trees were also observed, which was consistent with local native flora. We also observed that differences in latitude or climate zones appeared to influence the geographic distributions of plant pathogenic species more than the presence of compatible host species, with the exception of Brassicaceae host family. There was an increased proportion of necrotrophic Ascomycete species in warmer and drier regions of central WA, compared to an increased proportion of biotrophic Basidiomycete species in cooler and wetter regions in southern WA.
Development of an Immunogenomic Landscape-Based Prognostic Index of Head and Neck Squamous Cell Carcinoma
Authors: Long Jinhua , Zhang Shichao , Zeng Xianlin , Ouyang Yan , Wang Yun , Hu Zuquan , Ye Yuannong , Wu Weili , Jin Feng , Zhou Shi , Zeng Zhu
Published: November 2020

Head and neck squamous cell carcinoma (HNSCC) is the eighth leading cancer by incidence worldwide, with approximately 700,000 new cases in 2018 (accounting for 11% of all cancers). The occurrence and development of tumors are closely related to the immunological function of the body and sensitivity to treatment schemes as well as prognosis. It is urgent for clinicians to systematically study patients’ immune gene maps to help select a treatment plan and analyze the potential to cure HNSCC. Here, the transcriptomic data of HNSCC samples were downloaded from The Cancer Genome Atlas (TCGA), and 4,793 genes differentially expressed in normal and cancer tissues of HNSCC were identified, including 1,182 downregulated and 3,611 upregulated genes. From these genes, 400 differentially expressed immune-related genes (IRGs) were extracted, including 95 downregulated genes and 305 upregulated genes. The prognostic values of IRGs were evaluated by univariate Cox analysis, and 236 genes that were significantly related to the overall survival (OS) of patients were identified. The signaling pathways that play roles in the prognosis of IRGs were investigated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, and the expression profiles of IRGs and OS in 499 HNSCC patients based on TCGA dataset were integrated. Potential molecular mechanisms and characteristics of these HNSCC-specific IRGs were further explored with the help of a new prognostic index based on IRGs developed by least absolute shrinkage and selection operator (LASSO) Cox analysis. A total of 64 hub genes (IRGs associated with prognosis) were markedly associated with the clinical outcome of HNSCC patients. KEGG functional enrichment analysis revealed that these genes were actively involved in several pathways, e.g., cytokine–cytokine receptor interaction, T-cell receptor signaling, and natural killer cell-mediated cytotoxicity. IRG-based prognostic signatures performed moderately in prognostic predictions. Interestingly, the prognostic index based on IRGs reflected infiltration by several types of immune cells. These data screened several IRGs of clinical significance and revealed drivers of the immune repertoire, demonstrating the importance of a personalized IRG-based immune signature in the recognition, surveillance, and prognosis of HNSCC.
Case Report: Acute Bulbar Palsy Plus Syndrome: A Guillain-Barré Syndrome Variant More Prone to Be a Subtype Than Overlap of Distinct Subtypes
Authors: Cao Qian , Chu Hong , Fu Xiujuan , Yao Jiajia , Xiao Zheman , Lu Zuneng
Published: November 2020

Objective: Acute bulbar palsy plus (ABPp) syndrome is a rare regional variant of Guillain-Barré syndrome (GBS) characterized by acute bulbar palsy combined with other cranial symptoms or ataxia without limb and neck weakness. We aim to investigate characteristics of ABPp syndrome and analyze its nosological position within the GBS spectrum.

Methods: A patient with ABPp syndrome was reported, and previous case reports of patients who met the criteria for ABPp syndrome from the literature were reviewed.

Results: A total of 28 patients were included in our study. Median age was 32 years. Most of the patients (78.6%) were from Asia, and 75.0% had preceding infection. The main accompanying symptoms were ophthalmoplegia (85.7%), facial palsy (60.7%), and ataxia (50.0%). There existed asymmetric weakness in the form of unilateral facial palsy (32.1%) and ptosis (3.6%). Approximately half of the patients had albuminocytological dissociation. All the tested patients were seropositive for antiganglioside antibodies, of which the two most common were immunoglobulin G (IgG) anti-GT1a (77.3%) and anti-GQ1b (59.1%) antibodies. Over one-third of the patients who underwent electrophysiological assessment showed subclinical neuropathy beyond cranial nerves. The outcome was generally favorable as 89.3% of patients made full recovery within 5 months.

Conclusion: The hitherto largest case series of ABPp syndrome advances our understanding of this disease. Serologically, the presence of IgG anti-GT1a and anti-GQ1b antibodies predicts and contributes to the disease. Phenotypically, ABPp syndrome is more prone to be a separate subtype of GBS than overlap of distinct subtypes and has the potential to complement current diagnostic framework of GBS.
High-Fat Diet Alters the Expression of Reference Genes in Male Mice
Authors: Fan Xiuqin , Yao Hongyang , Liu Xuanyi , Shi Qiaoyu , Lv Liang , Li Ping , Wang Rui , Tang Tiantian , Qi Kemin
Published: November 2020

Quantitative PCR (qPCR), the most accurate and sensitive technique for quantifying mRNA expression, and choice of appropriate reference genes for internal error controlling in qPCR are essential to understanding the molecular mechanisms that drive the obesity epidemic and its comorbidities. In this study, using the high-fat diet (HFD)-induced obese mouse model, we assessed the expression of 10 commonly used reference genes to validate gene-expression stability in adipose tissue, liver, and muscle across different time points (4, 8, 12, and 16 weeks after HFD feeding) during the process of obesity. The data were analyzed by the GeNorm, NormFinder, BestKeeper, and Delta-Ct method, and the results showed that the most stable reference genes were different for a specific organ or tissue in a specific time point; however, PPIA, RPLP0, and YWHAZ were the top three most stable reference genes in qPCR experiments on adipose, hepatic tissues, and muscles of mice in diet-induced obesity. In addition, the mostly used genes ACTB and GAPDH were more unstable in the fat and liver, the ACTB mRNA levels were increased in four adipose tissues, and the GAPDH mRNA levels were decreased in four adipose tissues and liver after HFD feeding. These results suggest that PPIA, RPLP0, or YWHAZ may be more appropriate to be used as reference gene than ACTB and GAPDH in the adipose tissue and liver of mice during the process of high-fat diet-induced obesity.
Discovery and Validation of a Metastasis-Related Prognostic and Diagnostic Biomarker for Melanoma Based on Single Cell and Gene Expression Datasets
Authors: Wan Qi , Liu Chengxiu , Liu Chang , Liu Weiqin , Wang Xiaoran , Wang Zhichong
Published: November 2020

Background

Single cell sequencing can provide comprehensive information about gene expression in individual tumor cells, which can allow exploration of heterogeneity of malignant melanoma cells and identification of new anticancer therapeutic targets.

Methods

Single cell sequencing of 31 melanoma patients in GSE115978 was downloaded from the Gene Expression Omniniub (GEO) database. First, the limma package in R software was used to identify the differentially expressed metastasis related genes (MRGs). Next, we developed a prognostic MRGs biomarker in the cancer genome atlas (TCGA) by combining univariate cox analysis and the least absolute shrinkage and selection operator (LASSO) method and was further validated in another two independent datasets. The efficiency of MRGs biomarker in diagnosis of melanoma was also evaluated in multiple datasets. The pattern of somatic tumor mutation, immune infiltration, and underlying pathways were further explored. Furthermore, nomograms were constructed and decision curve analyses were also performed to evaluate the clinical usefulness of the nomograms.

Results

In total, 41 MRGs were screened out from 1958 malignant melanoma cell samples in GSE115978. Next, a 5-MRGs prognostic marker was constructed and validated, which show more effective performance for the diagnosis and prognosis of melanoma patients. The nomogram showed good accuracies in predicting 3 and 5 years survival, and the decision curve of nomogram model manifested a higher net benefit than tumor stage and clark level. In addition, melanoma patients can be divided into high and low risk subgroups, which owned differential mutation, immune infiltration, and clinical features. The low risk subgroup suffered from a higher tumor mutation burden (TMB), and higher levels of T cells infiltrating have a significantly longer survival time than the high risk subgroup. Gene Set Enrichment Analysis (GSEA) revealed that the extracellular matrix (ECM) receptor interaction and epithelial mesenchymal transition (EMT) were the most significant upregulated pathways in the high risk group.

Conclusions

We identified a robust MRGs marker based on single cell sequencing and validated in multiple independent cohort studies. Our finding provides a new clinical application for prognostic and diagnostic prediction and finds some potential targets against metastasis of melanoma.
Clinical Factors Associated With Chronic Pain in Communicative Adults With Cerebral Palsy: A Cross-Sectional Study
Authors: Chin Eric M. , Lenz Colleen , Ye Xiaobu , Campbell Claudia M. , Stashinko Elaine , Jantzie Lauren L. , Gerner Gwendolyn , Hoon Alexander H. , Robinson Shenandoah
Published: November 2020

Chronic pain is prevalent in adults with cerebral palsy. We aimed to explore associations between chronic pain and somatosensory, motor, cognitive, etiologic, and environmental factors in adults with cerebral palsy. This cross-sectional study enrolled 17 adult participants with cerebral palsy (mean age 31 years; 8 female; Gross Motor Functional Classification Status levels I-V) able to self-report and 10 neurotypical adult volunteers (mean age 34 years; 9 female). Participants reported pain characteristics, demographics, and affective factors. Physical examination included somatosensory and motor evaluation. Between-group comparisons used a ranksum test, and correlation analyses estimated effect size in terms of shared variance (ρ2). Individuals with cerebral palsy reported greater pain intensity, neuropathic qualities, and nociceptive qualities than control participants. Higher pain intensity was associated with female gender (ρ2 = 16%), anxiety/depression symptoms (ρ2 = 10%), and lower household income (ρ2 = 19%). It was also associated with better communicative ability (ρ2 = 21%), spinothalamic (sharp/temperature) sensory abnormalities (ρ2 = 33%), and a greater degree of prematurity (ρ2 = 17%). This study highlights similarity of chronic pain associations in people with cerebral palsy with patterns seen in other populations with chronic pain. Spinothalamic sensory abnormalities suggest central pain mechanisms.
Social Media Use in Adolescents With Functional Abdominal Pain
Authors: Samuel Eshan , Lahiri Sharmistha , Hashmi Syed , Navarro Fernando
Published: November 2020

Social media use is increasing in children in the U.S., which could be related to the high prevalence of functional gastrointestinal disorders in this population.

Objective: To investigate the relationship of social media use with the severity of gastrointestinal symptoms in patients with a functional abdominal pain or irritable bowel syndrome diagnosis.

Study Design: We administered a questionnaire to collect information about screen time, demographics, and a modified Validated Varni PedsQL Gastrointestinal symptom scale which assesses the severity of gastrointestinal (GI) symptoms.

Results: We surveyed a total of 59 subjects, which included 26 subjects with functional abdominal pain and 33 age-matched healthy controls. The median score across all 8 scales was about a third less for cases (median: 63; IQR: 55–78) than controls (median: 93; IQR: 83–95) (p < 0.001). Mean screen time in the study group (341 min/day) was very similar to that in the control group (331 min/day). There was no statistically significant association between screen time per day and the number of platforms used for either the cases or controls. YouTube (92%) and Instagram (88%) were the first and second most popular platforms used by the children with functional abdominal pain; Instagram (97%) and Snapchat (82%) were the most popular platforms in the healthy controls. Interestingly, social media were more often used for entertainment, reading, and productivity by the children with functional abdominal pain (p < 0.05).

Conclusion: The amount of screen time/day and the number of social media platforms used does not correlate with the severity of abdominal pain and other GI symptoms in adolescents with FGID. Further research will be needed to confirm if the platforms are used differently by children with functional gastrointestinal disorder.