bluuebunny/crossref_metadata_2025 huggingface dataset:
A Chiral Lanthanide Tag for Stable and Rigid Attachment to Single Cysteine Residues in Proteins for NMR, EPR and Time‐Resolved Luminescence Studies
Authors: Herath Iresha D. , Breen Colum , Hewitt Sarah H. , Berki Thomas R. , Kassir Ahmad F. , Dodson Charlotte , Judd Martyna , Jabar Shereen , Cox Nicholas , Otting Gottfried , Butler Stephen J.
Published: June 2021

A lanthanide‐binding tag site‐specifically attached to a protein presents a tool to probe the protein by multiple spectroscopic techniques, including nuclear magnetic resonance, electron paramagnetic resonance and time‐resolved luminescence spectroscopy. Here a new stable chiral LnIII tag, referred to as C12, is presented for spontaneous and quantitative reaction with a cysteine residue to generate a stable thioether bond. The synthetic protocol of the tag is relatively straightforward, and the tag is stable for storage and shipping. It displays greatly enhanced reactivity towards selenocysteine, opening a route towards selective tagging of selenocysteine in proteins containing cysteine residues. Loaded with TbIII or TmIII ions, the C12 tag readily generates pseudocontact shifts (PCS) in protein NMR spectra. It produces a relatively rigid tether between lanthanide and protein, which is beneficial for interpretation of the PCSs by single magnetic susceptibility anisotropy tensors, and it is suitable for measuring distance distributions in double electron–electron resonance experiments. Upon reaction with cysteine or other thiol compounds, the TbIII complex exhibits a 100‐fold enhancement in luminescence quantum yield, affording a highly sensitive turn‐on luminescence probe for time‐resolved FRET assays and enzyme reaction monitoring.
A fast sequential algorithm for the matrix chain ordering problem
Authors: Lacmou Zeutouo Jerry , Kengne Tchendji Vianney , Myoupo Jean Frédéric
Published: June 2021

This article presents a fast sequential algorithm for the matrix chain ordering problem. Our solution is based on Yao's sequential algorithm that solves this problem in time by reducing the total number of distinct subproblems to be performed. We solve them fastly by avoiding some unnecessary computations. Our strategy consists in organizing the evaluation of the subproblems according to their dependencies instead of their precedence order as in the previous solutions. In many cases, our solution runs in time. An experimental study is conducted to benchmark the performance of our algorithm by measuring the average of the results obtained on five random data sets. This shows that our algorithm is 18.93 faster than Yao's sequential algorithm and 5.07 faster than the previous best CGM‐based parallel solutions on 32 processors.
Prognostic impact of Clinical Frailty Scale in patients with heart failure with preserved ejection fraction
Authors: Sunaga Akihiro , Hikoso Shungo , Yamada Takahisa , Yasumura Yoshio , Uematsu Masaaki , Tamaki Shunsuke , Abe Haruhiko , Nakagawa Yusuke , Higuchi Yoshiharu , Fuji Hisakazu , Mano Toshiaki , Kurakami Hiroyuki , Yamada Tomomi , Kitamura Tetsuhisa , Sato Taiki , Oeun Bolrathanak , Kida Hirota , Kojima Takayuki , Sotomi Yohei , Dohi Tomoharu , Okada Katsuki , Suna Shinichiro , Mizuno Hiroya , Nakatani Daisaku , Sakata Yasushi ,   OCVC‐Heart Failure Investigators
Published: June 2021

Aims

Frailty is associated with prognosis of cardiovascular diseases. However, the significance of frailty in patients with heart failure with preserved ejection fraction (HFpEF) remains to be elucidated. The purpose of this study was to examine the prognostic significance of the Clinical Frailty Scale (CFS) in real‐world patients with HFpEF using data from a prospective multicentre observational study of patients with HFpEF (PURSUIT‐HFpEF study).

Method and Results

We classified 842 patients with HFpEF enrolled in the PURSUIT‐HFpEF study into two groups using CFS. The registry enrolled patients hospitalized with a diagnosis of decompensated heart failure. Median age was 82 [interquartile range: 77, 87], and 45% of the patients were male. Of 842 patients, 406 were classified as high CFS (CFS ≥ 4, 48%) and 436 as low CFS (CFS ≤ 3, 52%). The primary endpoint was the composite of all‐cause mortality and heart failure admission. Secondary endpoints were all‐cause mortality and heart failure admission. Patients with high CFS were older (85 vs. 79 years, P < 0.001), predominantly female (65% vs. 46%, P < 0.001) and more likely to have New York Heart Association (NYHA) ≥ 2 (75% vs. 53%, P < 0.001) and a higher level of NT‐proBNP (1360 vs 838 pg/mL, P < 0.001) than those with low CFS. Patients with high CFS had a significantly greater risk of composite endpoint (Kaplan–Meier estimated 1‐year event rate 39% vs. 23%, log‐rank P < 0.001), all‐cause mortality (Kaplan–Meier estimated 1‐year event rate 17% vs. 7%, log‐rank P < 0.001) and heart failure admission (Kaplan–Meier estimated 1‐year event rate 28% vs. 19%, log‐rank P = 0.002) than those with low CFS. Multivariable Cox regression analysis revealed that high CFS was significantly associated with composite endpoint (adjusted HR 1.92, 95% CI 1.35–2.73, P < 0.001), all‐cause mortality (adjusted HR 2.54, 95% CI 1.39–4.66, P = 0.003) and heart failure admission (adjusted HR 1.55, 95% CI 1.03–2.32, P = 0.035) even after adjustment for covariates. Moreover, change in CFS grade was also significantly associated with composite endpoint (adjusted HR 1.23, 95% CI 1.11–1.36, P < 0.001), all‐cause mortality (adjusted HR 1.32, 95% CI 1.13–1.55, P = 0.001) and heart failure admission (adjusted HR 1.15, 95% CI 1.02–1.30, P = 0.021).

Conclusions

Frailty assessed by the CFS was associated with poor prognosis in patients with HFpEF.
Recent Advances in Electrochemical Sensors for Mycotoxin Detection in Food
Authors: Chen Xiao , Wu Huimin , Tang Xiaoqian , Zhang Zhaowei , Li Peiwu
Published: June 2021

Mycotoxins pose a grave global threat to human life and health by contaminating food and feed and cause enormous losses in healthcare and trading. Trace mycotoxin concentrations and diverse matrices in food make identification and measurement challenges, necessitating highly specific and sensitive detection methods. Electrochemical (EC) sensors are characterized by simple operation, outstanding sensitivity, low cost, and facile miniaturization and have become a promising strategy for addressing specificity and sensitivity in detection. Recent studies on EC sensors for mycotoxin detection for food safety are reviewed here. First, we summarize the fabrication of EC sensors and techniques with enhanced specificity and sensitivity. Then, we review state‐of‐the‐art EC sensors for detecting major mycotoxins. Challenges and opportunities for this technology are further discussed. Finally, in‐depth information is provided on using EC sensors to detect mycotoxins for food safety, as well as the development of EC sensors for academic study and practical application.
COVID‐19 sniffer dog experimental training: Which protocol and which implications for reliable sidentification?
Authors: Angeletti Silvia , Travaglino Francesco , Spoto Silvia , Pascarella Maria Chiara , Mansi Giorgia , De Cesaris Marina , Sartea Silvia , Giovanetti Marta , Fogolari Marta , Plescia Davide , Macera Massimiliano , Incalzi Raffaele Antonelli , Ciccozzi Massimo
Published: June 2021

The introduction of trained sniffer dogs for COVID‐19 detection could be an opportunity, as previously described for other diseases. Dogs could be trained to detect volatile organic compounds (VOCs), the whiff of COVID‐19. Dogs involved in the study were three, one male and two females from different breeds, Black German Shepherd, German Shepherd, and Dutch Shepherd. The training was performed using sweat samples from SARS‐CoV2 positive patients and from SARS‐Cov2 free patients admitted at the University Hospital Campus Bio‐medico of Rome. Gauze with sweat was collected in a glass jar with a metal top and put in metal boxes used for dog training. The dog training protocol was performed in two phases: the olfactory conditioning and the olfactory discrimination research. The training planning was focused on the switch moment for the sniffer dog, the moment when the dog was able to identify VOCs specific for COVID‐19. At this time, the dog was able to identify VOCs specific for COVID‐19 with significant reliability, in terms of the number of correct versus incorrect (p < 0.0001) reporting. In conclusion, this protocol could provide a useful tool for sniffer dogs' training and their introduction in a mass screening context. It could be cheaper and faster than a conventional testing method.
High‐Efficiency Drive for IPMSM Considering Copper Loss and Iron Loss
Authors: Zhang Yunfei , Qi Rong
Published: June 2021

This paper presents a maximum efficiency algorithm (MEA), aiming at minimizing both copper loss and iron loss, for the interior permanent magnet synchronous motor (IPMSM) drive system. The equivalent circuit model is utilized to reach the optimal dq‐current function with the optimal process. Besides, the current–voltage limitation algorithm for the MEA is proposed to solve the current limitation and the voltage limitation issues. The feasible region for the MEA is the intersection of the maximum current region and the maximum voltage region. With the IPMSM test platform, the validated experiments and efficiency tests were implemented to evaluate the proposed strategy. The experiments indicate the MEA operation is effective and feasible to improve the efficiency of the IPMSM. Besides, the feasible operating region of the IPMSM can be extended by the MEA. With the advantage of improving efficiency and extending the operating region, the MEA is suitable for applying the IPMSM drive system.
Chemical-potential-assisted particle production in FRW spacetimes
Authors: Sou Chon Man , Tong Xi , Wang Yi
Published: June 2021

Abstract

We analyze gravitational particle production assisted by chemical potential. By utilizing the uniformly smoothed Stokes-line method and Borel summation, we gain insight into the fine-grained history of enhanced particle production. Analytic/semi-analytic formulae describing the production amount, time and width are obtained for both spin-1 and spin-1/2 particles in various FRW spacetimes. Our work also serves as a concrete demonstration of the uniformly smoothed Stokes-line method applied to cosmology.
Ökonomische Auswirkung der COVID-19-Pandemie in der Allgemein- und Viszeralchirurgie
Authors: Binder Johannes , Brunner Maximilian , Maak Matthias , Denz Axel , Weber Georg F. , Grützmann Robert , Krautz Christian
Published: June 2021

Hintergrund

Bereits während der ersten Welle der COVID-19-Pandemie wurden die deutschen Krankenhäuser dazu aufgefordert, ihre elektiven Operationskapazitäten einzuschränken, um eine Überlastung des Gesundheitswesens abzuwenden. Im März 2020 wurden mit dem COVID-19-Krankenhausentlastungsgesetz finanzielle Hilfen zum Ausgleich dieser Einschränkungen vereinbart. Die Auswirkungen dieser Maßnahmen wurden in dieser Studie regional untersucht.

Material und Methoden

Es wurden die Leistungsdaten und Erlöskennzahlen der Klinik für Allgemein- und Viszeralchirurgie des Universitätsklinikums Erlangen (UKER) und der Chirurgischen Abteilung des Kreiskrankenhauses St. Anna Höchstadt/Aisch (KKH) im Zeitraum 01.04. bis 30.06.2019 mit denen des Jahres 2020 verglichen.

Ergebnisse

Es zeigte sich eine deutliche Reduktion der Bettenauslastung und der Fallzahlen stationär behandelter Patienten. Letztere sanken um 20,06 % im UKER bzw. 60,76 % im KKH. Nichtonkologische elektive Operationen nahmen um 33,04 % (UKER) bzw. 60,87 % (KKH) ab. Die Anzahl der Notfalleingriffe blieb am UKER unverändert und verringerte sich am KKH um 51,58 %.Die Erlöse aus DRG („diagnosis-related groups“) sanken um 22,12 % (UKER) und 54 % (KKH). Nach Berücksichtigung der Ausgleichszahlungen und Einsparungen aus variablen Sachkosten verzeichnete das UKER einen Verlust von −3,87 %, das KKH erreichte hingegen einen positiven Erlöseffekt von 6,5 %.

Diskussion

Die nichtselektive Einschränkung des elektiven Operationsbetriebs beeinflusste die Patientenversorgung und die Erlöskennzahlen an beiden Standorten signifikant. In Bezug auf die Schaffung von Intensivkapazitäten erscheint diese ungezielte Maßnahme jedoch nicht effizient. Zudem führte die einheitliche Freihaltepauschale zu einer unausgeglichenen Verteilung der finanziellen Hilfen zwischen den untersuchten Kliniken.
Association between cerebral perfusion and paediatric postoperative cerebellar mutism syndrome after posterior fossa surgery—a systematic review
Authors: Ahmadian Narjes , van Baarsen K. M. , Robe P. A. J. T. , Hoving E. W.
Published: June 2021

Background

Paediatric postoperative cerebellar mutism syndrome (ppCMS) is a common complication following the resection of a cerebellar tumour in children. It is hypothesized that loss of integrity of the cerebellar output tracts results in a cerebello-cerebral “diaschisis” and reduced function of supratentorial areas of the brain.

Methods

We performed a systematic review of the literature according to the PRISMA guidelines, in order to evaluate the evidence for hypoperfusion or hypofunction in the cerebral hemispheres in patients with ppCMS. Articles were selected based on the predefined eligibility criteria and quality assessment.

Results

Five studies were included, consisting of three prospective cohort studies, one retrospective cohort study and one retrospective case control study. Arterial spin labelling (ASL) perfusion MRI, dynamic susceptibility contrast (DSC) perfusion MRI and single photon emission computed tomography (SPECT) were used to measure the cerebral and cerebellar tissue perfusion or metabolic activity. Reduced cerebral perfusion was predominantly demonstrated in the frontal lobe.

Conclusions

This systematic review shows that, after posterior fossa tumour resection, cerebral perfusion is reduced in ppCMS patients compared to patients without ppCMS. Well-powered prospective studies, including preoperative imaging, are needed to ascertain the cause and role of hypoperfusion in the pathophysiology of the syndrome.
Metabolic cost in healthy fit older adults and young adults during overground and treadmill walking
Authors: Das Gupta Sauvik , Bobbert Maarten , Faber Herre , Kistemaker Dinant
Published: June 2021

Purpose

The purpose of this study was to determine whether net metabolic cost of walking is affected by age per se.

Methods

We selected 10 healthy, active older adults (mean age 75 years) and 10 young adults (mean age 26 years), and determined their preferred overground walking speed. On the same day, in a morning and afternoon session, we had them walk at that speed overground and on a treadmill while we measured oxygen consumption rate. From the latter we subtracted the rate in sitting and calculated net metabolic cost.

Results

Anthropometrics were not different between the groups nor was preferred walking speed (1.27 m s−1 both groups). There was no difference in net metabolic cost of overground walking between older and young adults (e.g., in the morning 2.64 and 2.56 J kg−1 m−1, respectively, p > 0.05). In the morning session, net metabolic cost of walking was higher on the treadmill than overground in our older adults by 0.6 J kg−1 m−1 (p < 0.05), but not in young adults.

Conclusion

First, there is no effect of age per se on metabolic cost of overground walking. Second, older adults tend to have higher metabolic cost of walking on a treadmill than walking overground at preferred speed, and adaptation may take a long time. The commonly reported age-related elevation of metabolic cost of walking may be due to confounding factors causing preferred walking speed to be lower in older adults, and/or due to older adults reacting differently to treadmill walking than young adults.
Effekt der COVID-19-Pandemie und des Lockdowns auf die Inzidenz von Herzinfarktpatienten in Deutschland – Ergebnisse einer Metaanalyse
Authors: Rattka Manuel , Dreyhaupt Jens , Winsauer Claudia , Stuhler Lina , Baumhardt Michael , Rottbauer Wolfgang , Imhof Armin
Published: June 2021

Hintergrund

Mit dem Beginn der COVID-19-Pandemie wurde weltweit über das Phänomen der rückläufigen Einweisungen von Herzinfarktpatienten berichtet. In dieser Metaanalyse wird die Häufigkeit der Vorstellungen von STEMI- und NSTEMI-Patienten in Deutschland während und vor der COVID-19-Pandemie analysiert.

Methoden

Es erfolgte eine selektive Literaturrecherche mit den Suchbegriffen „COVID“ und „myocardial infarction“ oder „STEMI“ oder „NSTEMI“ und „Germany“ in PubMed, Web of Science und Embase.

Ergebnisse

Basierend auf unserer Suchstrategie, konnten aus 40 identifizierten Studien 5 in unsere Metaanalyse aufgenommen werden. Diese ergab, dass die Häufigkeit der Krankenhauseinweisungen von Patienten mit akutem Myokardinfarkt in Deutschland während der Pandemie signifikant reduziert war (Inzidenzratenverhältnis [Incidence Rate Ratio, IRR] = 0,849, 95%-Konfidenzintervall: 0,827–0,872). Dies traf sowohl auf Patienten mit STEMI (IRR = 0,875, 95%-Konfidenzintervall: 0,837–0,914) als auch auf Patienten mit NSTEMI (IRR = 0,760, 95%-Konfidenzintervall: 0,633–0,911) zu.

Schlussfolgerung

In der vorliegenden Metaanalyse konnten wir zeigen, dass auch in Deutschland während der COVID-19-Pandemie die Häufigkeit der Krankenhauseinweisungen von Herzinfarktpatienten drastisch rückläufig war. Während der noch andauernden Pandemie ist es essenziell, die Bevölkerung weiterhin über die Symptome eines Herzinfarktes und die Dringlichkeit der akuten medizinischen Versorgung zu informieren und aufzuklären, um einer potenziellen Gefährdung von Herzinfarktpatienten vorzubeugen.
Experimental study of one-step economical retarded sandstone acid
Authors: Yang FuLin
Published: June 2021

The objective of this study is to experimentally evaluate a new acid combination of HEDP: CH3COOH as a retarded acid to minimize some limitations of high-temperature sandstone acidizing, such as fast acid-rock reaction and secondary precipitation pipeline corrosion. In this work, the acid–base titration, core-powder solubility test, scale deposition test, corrosion rate measurement and corefloods were carried out to evaluate the performances of the acid combination, including acidity characteristics, retarded performance, preventing scale rate, corrosivity and improving permeability. And then the microstructure and mineral content in sandstone samples were observed and analyzed with SEM–EDS. The results of evaluation tests indicated that the new acid combination has excellent performances on retarded rate, preventing scale deposition, permeability enhancement and lower corrosivity, comparing with conventional mud acid. The results of SEM and EDS showed that the microstructure and mineral content of sandstone changed after acid treatment. Compared with mud acid, the new acid system can react more with small particles on sandstone surface and less with the skeleton of samples and the decrease in the contents of Mg, Al, Na, K, Ca and Fe is relatively lower.
Imagine a school: Children draw and explain the ideal environmental school
Authors: Gal Adiv , Gan Dafna
Published: June 2021

Using drawings and accompanying written and oral explanations by third- and sixth-grade students, this phenomenological study is an examination of the children’s perception of the ideal environmental school. Analysis of the 128 features in the drawing yielded four categories: (1) physical – with natural areas and outdoor learning, (2) cognitive – core subjects and environmental ones, (3) emotional – the students’ feelings and the spaces for releasing stress and energy and (4) educational – environmental education (EE) includes a variety of pedagogies, features of nature and environmental solutions. While the drawings and explanations presented the school as the children know it, without boundary-breaking imagination and creativity, they also showed a desire for a positive school atmosphere, defined as essential to holistic EE and to leading environmental change. The positive atmosphere, nature and the environmental spaces can be the foundation of developing EE that is not fear based, which often generates helplessness and prevents action. The recommendations emphasise the need to enhance positive thinking and not to focus only on fear tactics as a means to enhance holistic EE and protect the environment.
Fragment(s) of the Past: Archives, Conflicts, and Civic Rights in Algiers, 1830–1870
Authors: Grangaud Isabelle
Published: June 2021

The first thirty years of the French conquest of Algeria witnessed the large-scale destruction of Algiers’s cultural heritage. Researching the processes by which this came about leads us to consider the conditions of production of two sources that refer to the period before the conquest: Les édifices religieux de l’ancien Alger (The Religious Edifices of Old Algiers), by Albert Devoulx, and the “Ottoman collection” of archives initially established by the same figure. This dual archaeology, based on the reconstitution of Devoulx’s activities during his lifetime, reveals a virulent struggle over civic rights and particularly over the appropriation of endowments established by the city’s religious institutions. The sources considered here were part and parcel of this struggle. By paying attention to the claims they set out and the interactions between them, it becomes possible to retrace the disappearance of the mosques of Algiers and to appreciate the true nature of these sources.
Natural Experiments and Causality in Economic History: On Their Relations to Theory and Temporality
Authors: Bourgeois-Gironde Sacha , Monnet Éric
Published: June 2021

A recent and influential research methodology, mainly endorsed by economists, proposes to renew historical analysis based on the notions of natural experiment and causality. It has the dual ambition of unifying various disciplines around a common understanding of causality in order to tackle major historical questions (such as the role of colonization, political regimes, or religion in economic development) and of making the analysis of history more scientific. The definition of causality it promotes—of the “interventionist” type—tends to liken historical events to laboratory experiments. This is articulated with a neo-institutionalist perspective aimed at measuring the long-term effects of past institutional changes, which are considered exogenous. In the first part of this article, we present the ambitions, contributions, methods, and hypotheses (implicit and explicit) of this approach, showing how it differs from more traditional quantitative economic history and placing it in the context of the recent empirical and neo-institutionalist “turns” of the economic discipline. In a second stage, we consider the criticism—often scathing—voiced by historians or economists against this method and its objectives. Finally, we emphasize the many difficulties posed by this approach when it comes to taking into account the historicity of phenomena, to producing general statements based on particular cases, and to providing a complete and coherent definition of causality in history.
Rewarding in International Law: It's About Time
Authors: Creamer Cosette D.
Published: June 2021

Anne van Aaken and Betül Simsek's article represents a significant contribution to the literature on international legal compliance. It pushes forward our understanding of the role that positive incentives play in its promotion, usefully highlights potential tradeoffs between positive and negative incentives, and identifies ways in which rewards and penalties may be employed together. While the authors suggest that a richer understanding of rewarding is useful for questions of institutional design, they purposefully focus on the compliance-side of the coin. This essay builds on their theoretical and conceptual ground-clearing to consider rewarding's implications for treaty negotiations and design. In doing so, it focuses on the role that time implicitly plays in the authors’ analysis and argues that assumptions about time horizons inflect all design calculations. For this reason, understandings of temporal dynamics should be foregrounded in both academic and policy realms.
Passionate souls: Elisabeth of Bohemia and René Descartes
Authors: Kitagawa Tomoko L.
Published: June 2021

The mathematical investigations of natural phenomena in the seventeenth century led to the inventions of calculus and probability. While we know the works of eminent natural philosophers and mathematicians such as Isaac Newton (1643-1727), we know little about the learned women who made important contributions in the seventeenth century. This article features Princess Elisabeth of Bohemia (1618-1680), whose intellectual ability and curiosity left a unique mark in the history of mathematics. While some of her family members were deeply involved in politics, Elisabeth led an independent, scholarly life, and she was a close correspondent of René Descartes (1596-1650) and Gottfried Leibniz (1646-1716).
The lost boarding pass and other practical problems
Authors: Grimmett Geoffrey R. , Stirzaker David R.
Published: June 2021

The world is amply supplied with probability teasers. These can mystify and intoxicate. Here are some classics.
Equality of areas among the ears of the Routh triangle
Authors: Hajja Mowaffaq
Published: June 2021

Figure 1 below shows a triangle ABC and three cevians AX, BY and CZ with intersection points
A Jar of Shaykhs’ Teeth: Medicine, Politics, and the Fragments of History in Kuwait
Authors: Goffman Laura Frances
Published: June 2021

This article examines ʿAbd al-Ilah al-Qinaʿi's early 20th-century melding of local, imperial, and transoceanic health practices alongside his 21st-century reemergence as a protonational Kuwaiti doctor. In the early 20th century, geographically and ideologically expansive horizons of health care fostered the emergence of hybrid medical practices. Facilitated by his access to multiple medical spheres and his proximity to Kuwait's rulers, ʿAbd al-Ilah was uniquely positioned to meet the demands of health-seeking consumers. In the 21st century, Kuwaitis' search for a national history that naturalizes claims to citizenship has resulted in ʿAbd al-Ilah's new designation as Kuwait's first doctor. Both processes—the interplay between local cultures of health and emergent institutions and the imagining of medical history as a nativist teleology—demonstrate how health-seeking and history-writing efforts of a range of historical actors have placed medicine at the center of politics in Kuwait.
mRNA-seq and miRNA-seq profiling analyses reveal molecular mechanisms regulating induction of fruiting body in Ophiocordyceps sinensis
Authors: Zhang Han , Yue Pan , Tong Xinxin , Bai Jing , Yang Jingyan , Guo Jinlin
Published: June 2021

Ophiocordyceps sinensishas been a source of valuable materials in traditional Asian medicine for over two thousand years. With recent global warming and overharvest, however, the availability of these wild fungi has decreased dramatically. While fruiting body ofO. sinensishas been artificially cultivated, the molecular mechanisms that govern the induction of fruiting body at the transcriptional and post-transcriptional levels are unclear. In this study, we carried out both mRNA and small RNA sequencing to identify crucial genes and miRNA-like RNAs (milRNAs) involved in the development of fruiting body. A total of 2875 differentially expressed genes (DEGs), and 71 differentially expressed milRNAs (DEMs) were identified among the mycoparasite complex, the sclerotium (ST) and the fruiting body stage. Functional enrichment and Gene Set Enrichment Analysis indicated that the ST had increased oxidative stress and energy metabolism and that mitogen-activated protein kinase signaling might induce the formation of fruiting body. Integrated analysis of DEGs and DEMs revealed that n_os_milR16, n_os_milR21, n_os_milR34, and n_os_milR90 could be candidate milRNAs that regulate the induction of fruiting body. This study provides transcriptome-wide insight into the molecular basis of fruiting body formation inO. Sinensisand identifies potential candidate genes for improving induction rate.
The risk of pancreatic adenocarcinoma following SARS-CoV family infection
Authors: Ebrahimi Sadrabadi Amin , Bereimipour Ahmad , Jalili Arsalan , Gholipurmalekabadi Mazaher , Farhadihosseinabadi Behrouz , Seifalian Alexander M.
Published: June 2021

COVID 19 disease has become a global catastrophe over the past year that has claimed the lives of over two million people around the world. Despite the introduction of vaccines against the disease, there is still a long way to completely eradicate it. There are concerns about the complications following infection with SARS-CoV-2. This research aimed to evaluate the possible correlation between infection with SARS-CoV viruses and cancer in an in-silico study model. To do this, the relevent dataset was selected from GEO database. Identification of differentially expressed genes among defined groups including SARS-CoV, SARS-dORF6, SARS-BatSRBD, and H1N1 were screened where the |Log FC| ≥ 1and p < 0.05 were considered statistically significant. Later, the pathway enrichment analysis and gene ontology (GO) were used by Enrichr and Shiny GO databases. Evaluation with STRING online was applied to predict the functional interactions of proteins, followed by Cytoscape analysis to identify the master genes. Finally, analysis with GEPIA2 server was carried out to reveal the possible correlation between candidate genes and cancer development. The results showed that the main molecular function of up- and down-regulated genes was “double-stranded RNA binding” and actin-binding, respectively. STRING and Cytoscape analysis presented four genes, PTEN, CREB1, CASP3, and SMAD3 as the key genes involved in cancer development. According to TCGA database results, these four genes were up-regulated notably in pancreatic adenocarcinoma. Our findings suggest that pancreatic adenocarcinoma is the most probably malignancy happening after infection with SARS-CoV family.
Effects of large herbivore grazing on relics of the presumed mammoth steppe in the extreme climate of NE-Siberia
Authors: Reinecke Jennifer , Ashastina Kseniia , Kienast Frank , Troeva Elena , Wesche Karsten
Published: June 2021

The Siberian mammoth steppe ecosystem changed dramatically with the disappearance of large grazers in the Holocene. The concept of Pleistocene rewilding is based on the idea that large herbivore grazing significantly alters plant communities and can be employed to recreate lost ecosystems. On the other hand, modern rangeland ecology emphasizes the often overriding importance of harsh climates. We visited two rewilding projects and three rangeland regions, sampling a total of 210 vegetation relevés in steppe and surrounding vegetation (grasslands, shrublands and forests) along an extensive climatic gradient across Yakutia, Russia. We analyzed species composition, plant traits, diversity indices and vegetation productivity, using partial canonical correspondence and redundancy analysis. Macroclimate was most important for vegetation composition, and microclimate for the occurrence of extrazonal steppes. Macroclimate and soil conditions mainly determined productivity of vegetation. Bison grazing was responsible for small-scale changes in vegetation through trampling, wallowing and debarking, thus creating more open and disturbed plant communities, soil compaction and xerophytization. However, the magnitude of effects depended on density and type of grazers as well as on interactions with climate and site conditions. Effects of bison grazing were strongest in the continental climate of Central Yakutia, and steppes were generally less affected than meadows. We conclude that contemporary grazing overall has rather limited effects on vegetation in northeastern Siberia. Current rewilding practices are still far from recreating a mammoth steppe, although large herbivores like bison can create more open and drier vegetation and increase nutrient availability in particular in the more continental Central Yakutian Plain.
Predictive modeling of parafoveal information processing during reading
Authors: Seelig Stefan , Risse Sarah , Engbert Ralf
Published: June 2021

Skilled reading requires information processing of the fixated and the not-yet-fixated words to generate precise control of gaze. Over the last 30 years, experimental research provided evidence that word processing is distributed across the perceptual span, which permits recognition of the fixated (foveal) word as well as preview of parafoveal words to the right of fixation. However, theoretical models have been unable to differentiate the specific influences of foveal and parafoveal information on saccade control. Here we show how parafoveal word difficulty modulates spatial and temporal control of gaze in a computational model to reproduce experimental results. In a fully Bayesian framework, we estimated model parameters for different models of parafoveal processing and carried out large-scale predictive simulations and model comparisons for a gaze-contingent reading experiment. We conclude that mathematical modeling of data from gaze-contingent experiments permits the precise identification of pathways from parafoveal information processing to gaze control, uncovering potential mechanisms underlying the parafoveal contribution to eye-movement control.
Impact of rs2414096 polymorphism of CYP19 gene on susceptibility of polycystic ovary syndrome and hyperandrogenism in Kashmiri women
Authors: Ashraf Sairish , Rasool Shayaq Ul Abeer , Nabi Mudasar , Ganie Mohd Ashraf , Masoodi Shariq R. , Amin Shajrul
Published: June 2021

Polycystic ovary syndrome (PCOS) is the most common reproductive endocrine disorder in pre-menopausal women having complex pathophysiology. Several candidate genes have been shown to have association with PCOS. CYP19 gene encodes a key steroidogenic enzyme involved in conversion of androgens into estrogens. Previous studies have reported contradictory results with regard to association of SNP rs2414096 in CYP19 gene with PCOS and hyperandrogenism in different ethnic populations. Present study was aimed to investigate the impact of SNP rs2414096 polymorphism of CYP19 gene on susceptibility of PCOS and hyperandrogenism in Kashmiri women. Further we also studied the genotypic-phenotypic association for various clinical and biochemical parameters of this polymorphism. Case control study. 394 PCOS cases diagnosed on the basis of Rotterdam criteria and age matched 306 healthy women. We found a significant differences in genotypic frequency (χ2 = 18.91, p < 0.05) as well as allele frequency (OR 0.63, CI 0.51–0.78, χ2 = 17.66, p < 0.05) between PCOS women and controls. The genotype–phenotype correlation analysis showed a significant difference in FG score (p = 0.047) and alopecia (p = 0.045) between the three genotypes. Also, the androgen excess markers like DHEAS (p < 0.001), Androstenedione (p < 0.001), Testosterone (p < 0.001) and FAI (p = 0.005) were significantly elevated in GG genotype and showed a significant difference in additive model in PCOS women. rs2414096 polymorphism of CYP19 gene is associated with the risk of PCOS as well as with clinical and biochemical markers of hyperandrogenism, hence suggesting its role in clinical manifestations of PCOS in Kashmiri women.
Quality of life in keratoconus: evaluation with Keratoconus Outcomes Research Questionnaire (KORQ)
Authors: Pinto Roberto Damian Pacheco , Abe Ricardo Yuji , Gomes Flávia Cid , Barbisan Paulo Rodolfo Tagliari , Martini Alexandre Fattah , de Almeida Borges Daniel , Fernandes Arthur Gustavo , Arieta Carlos Eduardo Leite , Alves Monica
Published: June 2021

To assess the quality of life of keratoconus patients using the Keratoconus Outcomes Research Questionnaire (KORQ), translated and validated in Portuguese language. The KORQ is the only validated keratoconus specific questionnaire and has a high rating for its psychometric properties. This cross-sectional study enrolled 100 keratoconus patients from a tertiary referral eye hospital between April 2018 and June 2019. Associations between age, sex, allergic conjunctivitis, keratoconus stage, best-corrected visual acuity (BCVA), maximum simulated keratometry (Kmax), steep keratometry (K2), pachymetry, treatments performed, hydrops, and KORQ scores were evaluated using univariate (Wilcoxon test and the Kruskal Wallis test) and multivariate linear regression with stepwise backward modeling. Lower KORQ scores are associated with better quality of life, whereas, higher scores are associated with greater impairment of functional activities and symptoms. Among the 100 patients, mild, moderate, and severe keratoconus were observed in 15%, 46% and 39% of participants, respectively. Univariate analysis showed lower function scores values, with male sex (p < 0.05) and both functional and symptom scores were significantly associated with BCVA < 0.3 (LogMAR) (p < 0.05). Multivariate analysis indicated significantly lower functional scores in individuals with BCVA < 0.3 (LogMAR) (p < 0.001) and those with a history of crosslinking treatment (p = 0.022), while symptom scores were only significantly associated with only BCVA < 0.3 (LogMAR) (p < 0.001). In patients with keratoconus, BCVA in the better eye and history of crosslinkig were factors associated with better quality of life scores using the KORQ.
Ocular pigmentation in humans, great apes, and gibbons is not suggestive of communicative functions
Authors: Caspar Kai R. , Biggemann Marco , Geissmann Thomas , Begall Sabine
Published: June 2021

Pigmentation patterns of the visible part of the eyeball, encompassing the iris and portions of the sclera, have been discussed to be linked to social cognition in primates. The cooperative eye hypothesis suggests the white sclera of humans to be a derived adaptive trait that enhances eye-mediated communication. Here, we provide a comparative analysis of ocular pigmentation patterns in 15 species of hominoids (humans, great apes & gibbons) that show marked differences in social cognition and quantify scleral exposure at the genus level. Our data reveals a continuum of eye pigmentation traits in hominoids which does not align with the complexity of gaze-mediated communication in the studied taxa. Gibbons display darker eyes than great apes and expose less sclera. Iridoscleral contrasts in orangutans and gorillas approach the human condition but differ between congeneric species. Contrary to recent discussions, we found chimpanzee eyes to exhibit a cryptic coloration scheme that resembles gibbons more than other apes. We reevaluate the evidence for links between social cognition and eye pigmentation in primates, concluding that the cooperative eye hypothesis cannot explain the patterns observed. Differences in scleral pigmentation between great apes and humans are gradual and might have arisen via genetic drift and sexual selection.
Multiscale modelling of cerebrovascular injury reveals the role of vascular anatomy and parenchymal shear stresses
Authors: Farajzadeh Khosroshahi Siamak , Yin Xianzhen , K. Donat Cornelius , McGarry Aisling , Yanez Lopez Maria , Baxan Nicoleta , J. Sharp David , Sastre Magdalena , Ghajari Mazdak
Published: June 2021

Neurovascular injury is often observed in traumatic brain injury (TBI). However, the relationship between mechanical forces and vascular injury is still unclear. A key question is whether the complex anatomy of vasculature plays a role in increasing forces in cerebral vessels and producing damage. We developed a high-fidelity multiscale finite element model of the rat brain featuring a detailed definition of the angioarchitecture. Controlled cortical impacts were performed experimentally and in-silico. The model was able to predict the pattern of blood–brain barrier damage. We found strong correlation between the area of fibrinogen extravasation and the brain area where axial strain in vessels exceeds 0.14. Our results showed that adjacent vessels can sustain profoundly different axial stresses depending on their alignment with the principal direction of stress in parenchyma, with a better alignment leading to larger stresses in vessels. We also found a strong correlation between axial stress in vessels and the shearing component of the stress wave in parenchyma. Our multiscale computational approach explains the unrecognised role of the vascular anatomy and shear stresses in producing distinct distribution of large forces in vasculature. This new understanding can contribute to improving TBI diagnosis and prevention.
CB1R activation in nucleus accumbens core promotes stress-induced reinstatement of cocaine seeking by elevating extracellular glutamate in a drug-paired context
Authors: Guzman Andrea S. , Avalos Maria P. , De Giovanni Laura N. , Euliarte Pia V. , Sanchez Marianela A. , Mongi-Bragato Bethania , Rigoni Daiana , Bollati Flavia A. , Virgolini Miriam B. , Cancela Liliana M.
Published: June 2021

Preclinical models of stress-induced relapse to drug use have shown that the dysregulation of glutamatergic transmission within the nucleus accumbens (NA) contributes notably to the reinstatement of cocaine-seeking behavior in rodents. In this sense, there has been increasing interest in the cannabinoid type-1 receptor (CB1R), due to its crucial role in modulating glutamatergic neurotransmission within brain areas involved in drug-related behaviors. This study explored the involvement of CB1R within the NA subregions in the restraint stress-induced reinstatement of cocaine-conditioned place preference (CPP), as well as in the regulation of glutamatergic transmission, by using a pharmacological approach and the in vivo microdialysis sampling technique in freely moving rats. CB1R blockade by the antagonist/inverse agonist AM251 (5 nmol/0.5 μl/side) or CB1R activation by the agonist ACEA (0.01 fmol/0.5 μl/side), prevented or potentiated restraint stress-induced reinstatement of cocaine-CPP, respectively, after local administration into NAcore, but not NAshell. In addition, microdialysis experiments demonstrated that restraint stress elicited a significant increase in extracellular glutamate in NAcore under reinstatement conditions, with the local administration of AM251 or ACEA inhibiting or potentiating this, respectively. Interestingly, this rise specifically corresponded to the cocaine-associated CPP compartment. We also showed that this context-dependent change in glutamate paralleled the expression of cocaine-CPP, and disappeared after the extinction of this response. Taken together, these findings demonstrated the key role played by CB1R in mediating reinstatement of cocaine-CPP after restraint stress, through modulation of the context-specific glutamate release within NAcore. Additionally, CB1R regulation of basal extracellular glutamate was demonstrated and proposed as the underlying mechanism.
Pathogenesis of hemorrhagic disease caused by elephant endotheliotropic herpesvirus (EEHV) in Asian elephants (Elephas maximus)
Authors: Guntawang Thunyamas , Sittisak Tidaratt , Kochagul Varankpicha , Srivorakul Saralee , Photichai Kornravee , Boonsri Kittikorn , Janyamethakul Thittaya , Boonprasert Khajohnpat , Langkaphin Warangkhana , Thitaram Chatchote , Pringproa Kidsadagon
Published: June 2021

Elephant endotheliotropic herpesvirus-hemorrhagic disease (EEHV-HD) is an acute fatal disease in elephants. Despite the fact that the underlying pathogenesis of EEHV-HD has been proposed, it remains undetermined as to what mechanisms drive these hemorrhagic and edematous lesions. In the present study, we have investigated and explained the pathogenesis of acute EEHV-HD using blood profiles of EEHV-HD and EEHV-infected cases, hematoxylin and eosin (H&E) stain, special stains, immunohistochemistry, quantitative polymerase chain reaction (PCR) and reverse transcriptase polymerase chain reaction (RT-PCR). It was found that EEHV genomes were predominantly detected in various internal organs of EEHV-HD cases. Damage to endothelial cells, vasculitis and vascular thrombosis of the small blood vessels were also predominantly observed. Increases in platelet endothelial cell adhesion molecules-1 (PECAM-1)- and von Willebrand factor (vWF)-immunolabeling positive cells were significantly noticed in injured blood vessels. The expression of pro-inflammatory cytokine mRNA was significantly up-regulated in EEHV-HD cases when compared to EEHV-negative controls. We have hypothesized that this could be attributed to the systemic inflammation and disruption of small blood vessels, followed by the disseminated intravascular coagulopathy that enhanced hemorrhagic and edematous lesions in EEHV-HD cases. Our findings have brought attention to the potential application of effective preventive and therapeutic protocols to treat EEHV infection in Asian elephants.
Immunomodulatory effects of different intravenous immunoglobulin preparations in chronic lymphocytic leukemia
Authors: Colado Ana , Elías Esteban Enrique , Sarapura Martínez Valeria Judith , Cordini Gregorio , Morande Pablo , Bezares Fernando , Giordano Mirta , Gamberale Romina , Borge Mercedes
Published: June 2021

Hypogammaglobulinemia is the most frequently observed immune defect in chronic lymphocytic leukemia (CLL). Although CLL patients usually have low serum levels of all isotypes (IgG, IgM and IgA), standard immunoglobulin (Ig) preparations for replacement therapy administrated to these patients contain more than 95% of IgG. Pentaglobin is an Ig preparation of intravenous application (IVIg) enriched with IgM and IgA (IVIgGMA), with the potential benefit to restore the Ig levels of all isotypes. Because IVIg preparations at high doses have well-documented anti-inflammatory and immunomodulatory effects, we aimed to evaluate the capacity of Pentaglobin and a standard IVIg preparation to affect leukemic and T cells from CLL patients. In contrast to standard IVIg, we found that IVIgGMA did not modify T cell activation and had a lower inhibitory effect on T cell proliferation. Regarding the activation of leukemic B cells through BCR, it was similarly reduced by both IVIgGMA and IVIgG. None of these IVIg preparations modified spontaneous apoptosis of T or leukemic B cells. However, the addition of IVIgGMA on in vitro cultures decreased the apoptosis of T cells induced by the BCL-2 inhibitor, venetoclax. Importantly, IVIgGMA did not impair venetoclax-induced apoptosis of leukemic B cells. Overall, our results add new data on the effects of different preparations of IVIg in CLL, and show that the IgM/IgA enriched preparation not only affects relevant mechanisms involved in CLL pathogenesis but also has a particular profile of immunomodulatory effects on T cells that deserves further investigation.