bluuebunny/crossref_metadata_2025 huggingface dataset:
The Anscombe-Lewis Debate: New Archival Sources Considered
Authors: Stockton Jim , Lipscomb Benjamin J.B.
Published: April 2021

Meeting from 26 January 1942 through 26 May 1972, the Oxford University Socratic Club was a fixture of Oxford intellectual life for three decades. Founded by Miss Stella Aldwinckle, chaplain to undergraduate women students for the Oxford Pastorate, the club was an immediate success and quickly became a favoured venue for students and faculty alike, with C.S. Lewis serving as club president and senior member (advisor) from its inception to December 1954. One of the club's most famous papers was delivered 2 February 1948, when twenty-eight-year-old Somerville philosopher G.E.M. Anscombe presented a critique of a key argument in Lewis's recently published Miracles (1947). Most of the critical literature on the event has come from Lewis biographers. Less has been written about Anscombe's perspective, one reason being a lack of primary evidence. Following a framing discussion of the Socratic Club's early years, Lewis's persona and role in the club, and Anscombe's early biography, this article presents three unpublished pieces of primary evidence – a letter by Anscombe, a remark about Lewis by Ludwig Wittgenstein, and a full transcription of the meeting minutes – before briefly considering the light they shed on the exchange between Anscombe and Lewis.
FARELERDE SKOPOLAMİNLE BOZULMUŞ ÖĞRENME VE BELLEK ÜZERİNE NÖROTENSİN AGONİSTİ PD149163’ÜN ETKİSİ
Authors: TOPUZ Ruhan Deniz , KAYA Oktay
Published: April 2021

Nörotensin (NT), santral sinir sisteminde nöromodülatör, nörotransmitter ve nörohormon olarak görev yapan bir tridekapeptittir. NT; vücut sıcaklığının düzenlenmesi, ağrı, motor aktivite, öğrenme ve bellek yapılanması gibi fizyolojik süreçlerde rol oynar. Bu çalışmada NT agonisti PD149163’ün akut ve kronik kullanımının skopolaminle oluşturulmuş bellek bozukluğu üzerine etkilerinin incelenmesi amaçlandı. Bu çalışma Trakya Üniversitesi Hayvan Deneyleri Yerel Etik kurulundan 2019.02.01 karar no ile onaylanmıştır. Çalışmada toplam 32 adet Balb/c türü erişkin erkek fare 4 gruba ayrıldı. Öğrenme ve bellek fonksiyonları Morris su labirenti testinde değerlendirildi. 7 gün boyunca skopolamin (1 mg/kg i.p.) uygulandıktan sonra akut ve kronik (7 gün, 4 mg/kg, i.p) PD149163 tedavisinin öğrenme ve bellek bozukluğunu geri döndürüp döndürmediği incelendi. Çalışmada yüzme eğitimlerinden elde edilen veriler, tekrarlayan ölçümler iki yönlü varyans analizi (ANOVA ) ile analiz edildi. Probe verileri tek yönlü varyans analizi ile değerlendirildi. Kronik PD149163 uygulamasının Morris su labirenti testinde ne öğrenme fazında ne de bellek fazında iyileştirici bir etkisi olmadı. Akut PD149163 uygulamasının skopolaminle oluşturulmuş bellek bozukluğu üzerine herhangi bir etkisi olmadı. Çalışmamızda NT agonistinin skopolaminle oluşturulan öğrenme ve bellek bozukluğunda düzeltici etkisi görülmemiştir. NT reseptörleri yeni ilaç hedefleri olarak değerlendirilmelerine karşın bu alanda yapılacak çok fazla sayıda çalışmaya ihtiyaç olduğu düşüncesindeyiz.
KÜKÜRT DİOKSİT DÜZEYLERİNİN KIRKLARELİ İL MERKEZİNDEKİ ÖLÜMLER ÜZERİNE ETKİSİNİN İNCELENMESİ
Authors: KARAGÖZOĞLU Seda , ASAV Engin
Published: April 2021

Hava kirliliği, çeşitli kimyasal süreçler sonucunda oluşan ürünler tarafından havanın doğal bileşiminin bozulmasıdır. Bu bozulma biyolojik çeşitliliği ve doğal yaşamı olumsuz yönde etkilemektedir. Hava kirliliğine sebep olan hava kirleticilerinin maruz kalma süresi, derişim ve kimyasal özelliklerine bağlı olarak insan sağlığı üzerinde olumsuz etkileri bulunmaktadır. Bu çalışmanın amacı; hava kirliliğine sebep olan moleküllerden biri olan kükürt dioksitin Kırklareli il merkezindeki ölümler üzerine etkisinin incelenmesidir. Araştırma örneklemini, Kırklareli il merkezindeki 01.02.2014-31.01.2019 tarihleri arasında gerçekleşen, 18-85 yaş arasındaki 1381 bulaşıcı olmayan doğal ölüm vakası oluşturmuştur. Kükürt dioksit (SO2) seviyelerine ilişkin veriler Çevre ve Şehircilik Bakanlığının hava kalitesi izleme ağının internet sitesinden sağlanmıştır. Kükürt dioksit seviyelerinin, belirtilen tarihlerdeki aylara göre dağılımı ve ölüm sayıları ile olan bağıntısının saptanması SPSS 22.0 yazılımı kullanılarak gerçekleştirilmiştir. Araştırmanın analiz sonuçlarında 2014-2019 yılları arasındaki bazı aylarda kükürt dioksit (SO2) düzeyleri Dünya Sağlık Örgütü’nün (DSÖ) belirlediği sınır değerinin üzerinde olsa da yıllık ortalamaların sınır değerlerinin altında kaldığı açıkça gözükmektedir. Ölüm sayılarının yıllara göre değişimi ile yıllık ortalama kükürt dioksit seviyeleri arasındaki bağıntının değerlendirilmesi, yorumlanması ve kıyaslanması bu sınır değerleri göz önüne alınarak yapılmıştır.
Exosomal Transfer of miR-185 Is Controlled by hnRNPA2B1 and Impairs Re-endothelialization After Vascular Injury
Authors: Si Yi , Liu Fei , Wang Dongqing , Fang Chao , Tang Xiao , Guo Baolei , Shi Zhenyu , Dong Zhihui , Guo Daqiao , Yue Jianing , Fu Weiguo
Published: April 2021

Dysfunction of endothelial cells (ECs) contributes to restenosis after vascular reconstruction for patients with coronary artery disease (CAD). The intercellular communication between ECs and vascular smooth muscle cells (VSMCs) might be critical in the development of restenosis and can be mediated by exosomes carrying functional microRNAs. miR-185 is reported to be associated with atherosclerosis, whether it plays a similar role in restenosis is unknown. In this study, we observed an elevated level of extracellular miR-185 in platelet-derived growth factor (PDGF)-stimulated VSMCs. The medium from PDGF-stimulated VSMCs promoted miR-185 expression in rat aortic ECs and inhibited EC angiogenesis. PDGF-stimulated VSMCs transferred miR-185 into ECs via exosomes. Furthermore, we found that the CXCL12 gene, a target of miR-185, is essential for the angiogenic potential of ECs. Exosomes derived from miR-185 mimic transfected VSMCs attenuated re-endothelialization after vascular injury. Moreover, we show that exosome-mediated miR-185 transfer is modulated by hnRNPA2B1. We also observed that hnRNPA2B1 is up-regulated during neointima formation and hnRNPA2B1 inhibition accelerates re-endothelialization and attenuates neointima formation following carotid injury. Taken together, our results indicate that exosomal miR-185 transfer from VSMCs to ECs is controlled by hnRNPA2B1 and impairs re-endothelialization after vascular injury.
PprA Protein Inhibits DNA Strand Exchange and ATP Hydrolysis of Deinococcus RecA and Regulates the Recombination in Gamma-Irradiated Cells
Authors: Rajpurohit Yogendra Singh , Sharma Dhirendra Kumar , Misra Hari S.
Published: April 2021

DrRecA and PprA proteins function are crucial for the extraordinary resistance to γ-radiation and DNA strand break repair in Deinococcus radiodurans. DrRecA mediated homologous recombination help in DNA strand break repair and cell survival, while the PprA protein confers radio-resistance via its roles in DNA repair, genome maintenance, and cell division. Genetically recA and pprA genes interact and constitute an epistatic group however, the mechanism underlying their functional interaction is not clear. Here, we showed the physical and functional interaction of DrRecA and PprA protein both in solution and inside the cells. The absence of the pprA gene increases the recombination frequency in gamma-irradiated D. radiodurans cells and genomic instability in cells growing under normal conditions. PprA negatively regulates the DrRecA functions by inhibiting DrRecA mediated DNA strand exchange and ATPase function in vitro. Furthermore, it is shown that the inhibitory effect of PprA on DrRecA catalyzed DNA strand exchange was not due to sequestration of homologous dsDNA and was dependent on PprA oligomerization and DNA binding property. Together, results suggest that PprA is a new member of recombination mediator proteins (RMPs), and able to regulate the DrRecA function in γ-irradiated cells by protecting the D. radiodurans genome from hyper-recombination and associated negative effects.
Organoids of the Female Reproductive Tract: Innovative Tools to Study Desired to Unwelcome Processes
Authors: Heremans Ruben , Jan Ziga , Timmerman Dirk , Vankelecom Hugo
Published: April 2021

The pelviperineal organs of the female reproductive tract form an essential cornerstone of human procreation. The system comprises the ectodermal external genitalia, the Müllerian upper-vaginal, cervical, endometrial and oviductal derivatives, and the endodermal ovaries. Each of these organs presents with a unique course of biological development as well as of malignant degeneration. For many decades, various preclinical in vitro models have been employed to study female reproductive organ (patho-)biology, however, facing important shortcomings of limited expandability, loss of representativeness and inadequate translatability to the clinic. The recent emergence of 3D organoid models has propelled the field forward by generating powerful research tools that in vitro replicate healthy as well as diseased human tissues and are amenable to state-of-the-art experimental interventions. Here, we in detail review organoid modeling of the different female reproductive organs from healthy and tumorigenic backgrounds, and project perspectives for both scientists and clinicians.
Shedding New Lights Into STED Microscopy: Emerging Nanoprobes for Imaging
Authors: Liu Yanfeng , Peng Zheng , Peng Xiao , Yan Wei , Yang Zhigang , Qu Junle
Published: April 2021

First reported in 1994, stimulated emission depletion (STED) microscopy has long been regarded as a powerful tool for real-time superresolved bioimaging . However, high STED light power (101∼3 MW/cm2) is often required to achieve significant resolution improvement, which inevitably introduces phototoxicity and severe photobleaching, damaging the imaging quality, especially for long-term cases. Recently, the employment of nanoprobes (quantum dots, upconversion nanoparticles, carbon dots, polymer dots, AIE dots, etc.) in STED imaging has brought opportunities to overcoming such long-existing issues. These nanomaterials designed for STED imaging show not only lower STED power requirements but also more efficient photoluminescence (PL) and enhanced photostability than organic molecular probes. Herein, we review the recent progress in the development of nanoprobes for STED imaging, to highlight their potential in improving the long-term imaging quality of STED microscopy and broadening its application scope. We also discuss the pros and cons for specific classes of nanoprobes for STED bioimaging in detail to provide practical references for biological researchers seeking suitable imaging kits, promoting the development of relative research field.
The Development of a Virtual World Problem-Based Learning Tutorial and Comparison With Interactive Text-Based Tutorials
Authors: Jivram Trupti , Kavia Sheetal , Poulton Ella , Hernandez Aurora Sésé , Woodham Luke A. , Poulton Terry
Published: April 2021

Collaborative learning through case-based or problem-based learning (PBL) scenarios is an excellent way to acquire and develop workplace knowledge associated with specific competencies. At St George's, University of London we developed an interactive online form of decision-based PBL (D-PBL) for our undergraduate medical course using web-based virtual patients (VPs). This method of delivery allowed students to consider options for clinical management, to take decisions and to explore the consequences of their chosen actions. Students had identified this as a more engaging type of learning activity compared to conventional paper-based/linear PBL and demonstrated improved exam performance in controlled trials. We explored the use of Second Life (SL), a virtual world and immersive 3D environment, as a tool to provide greater realism than our interactive image and text-based D-PBL patient cases. Eighteen separate tutorial groups were provided with their own experience of the same patient scenario in separate locations within the virtual world. The study found that whilst a minority of students reported that the Second Life experience felt more realistic, most did not. Students favored the simpler interaction of the web-based VPs, which already provided them with the essential learning needed for practice. This was in part due to the time proximity to exams and the extra effort required to learn the virtual world interface. Nevertheless, this study points the way towards a scalable process for running separate PBL sessions in 3D environments.
Temperature Induced Physiological Reaction Norms of the Coccolithophore Gephyrocapsa oceanica and Resulting Coccolith Sr/Ca and Mg/Ca Ratios
Authors: Müller Marius N. , Blanco-Ameijeiras Sonia , Stoll Heather M. , Mendez-Vicente Ana , Lebrato Mario
Published: April 2021

Coccolithophores are one of the major contributors to the pelagic production of calcium carbonate and their fossilized remains are a key component of the biogeochemical cycles of calcium (Ca), magnesium (Mg), and other divalent cations present in the intracellular precipitated calcitic structures (coccoliths). The geochemical signature of coccoliths (e.g., Sr/Ca and Mg/Ca ratios) is used as paleoproxy to reconstruct past environmental conditions and to understand the underlying physiological precipitation kinetics. Here, we present the elemental fractionation of Sr and Mg in calcite of the coccolithophore Gephyrocapsa oceanica from controlled laboratory experiments applying an extended temperature gradient (12 to 27°C). The physiological reaction norm of G. oceanica, in terms of growth rate, exhibited optimum behavior while the partition coefficient of Sr (DSr) was linearly correlated with temperature and DMg indicated no specific trend. Our results indicate: (1) a presumably secondary physiological control of DSr, and (2) the importance of calibrating coccolithophore-based proxies using experiments that include the full physiological reaction norms (i.e., a possible non-linear response) to environmental drivers (e.g., temperature, salinity, and pH, etc.). The presented results contribute to an improved understanding of the underlying physiological kinetics involved in regulating coccolith elemental fractionation and give additional implications for designing future laboratory experiments to calibrate and apply coccolithophore based paleoproxies on the fossil sediment record.
Re-Evaluating the Surface Rupture and Slip Distribution of the AD 1609 M7 1/4 Hongyapu Earthquake Along the Northern Margin of the Qilian Shan, NW China: Implications for Thrust Fault Rupture Segmentation
Authors: Huang Xiongnan , Yang Xiaoping , Yang Haibo , Hu Zongkai , Zhang Ling
Published: April 2021

The Hexi Corridor is located beyond the northeastern edge of the Tibetan Plateau, and it is bounded by a series of active thrusts along the northern margin of the Qilian Shan and the southern piedmont of the Longshou Shan. Historically, five destructive earthquakes have occurred along the Hexi Corridor, which indicates that this region poses high potential seismic risks. The 1609 Hongyapu earthquake occurred along the Fodongmiao-Hongyazi fault in the northern Qilian Shan, China, and it killed more than 840 people and destroyed a large number of buildings. Presently, there are different opinions as to the distribution and length of the surface rupture of this event along the Fudongmiao–Hongyazi fault. Thus, we searched all of the fault scarps on the Holocene surfaces and suspected surface rupture locations related to the 1609 earthquake based on previous studies and developed detailed remote-sensing interpretations along the fault. An abundance of north-facing scarps on the younger fans and terrace faces, slightly higher than the active modern stream bed, were found along the Fodongmiao-Hongyazi fault in the area ranging from the Hongshuiba River (39.52°N, 98.41°E) in the west to the Shuiguan River (39.07°N, 99.37°E) in the east. Based on our research, we estimate a surface rupture length as ∼98 km based on the distribution of the fault scarps on Late Holocene surfaces and constraints provided by age dating. Most of the surface ruptures are preserved as fault scarps and indicate an average vertical surface offset of ∼1.0 m, a value found consistently in three segments of the fault. The surface rupture features indicate that segments of the fault ruptured together coseismically during the 1609 earthquake, i.e., a multisegment rupture. Using the surface fault traces, length of 98 or 90 km (without the Shuiguan River section), dip of 30° inferred from previous reflection profiles, a rigidity of 3.3 × 1010 N/m2, and dip slip average as 1.9 m converted from our observations of the offsets, we computed the magnitude of this event as ca. Mw 7.2–Mw 7.4.
Climate Patterns in the World’s Longest History of Storm-Erosivity: The Arno River Basin, Italy, 1000–2019 CE
Authors: Diodato Nazzareno , Ljungqvist Fredrik Charpentier , Bellocchi Gianni
Published: April 2021

Rainfall erosivity causes considerable environmental damage by driving soil loss. However, the long-term evolution of erosive forcing (over centennial to millennial time-scales) remains essentially unknown. Using a rainfall erosivity model (REMARB), this study simulates the variability of rainfall erosivity in Arno River Basin (ARB), Italy, a Mediterranean fluvial basin, for the period 1000–2019 CE resulting in the world’s longest time-series of erosivity. The annual estimates show a noticeable and increasing variability of rainfall erosivity during the Little Ice Age (∼1250–1849), especially after c. 1490, until the end of 18th century. During this cold period, erosive forcing reached ∼1600 MJ mm hm−2 h−1 yr−1once every four years, and ∼3000 MJ mm hm−2 h−1 yr−1once every 20 years. The extremes of rainfall erosivity (the 98th percentile) followed a similar increasing trend, with an acceleration of the hydrological hazard (erosivity per unit of rainfall) during the 20th century. The comparison ofREMARBoutput with the sediment yield of the basin (1951–2010) confirmed the model’s ability to predict geomorphological effects in the ARB. Thus, our methodology could be applied to simulate erosivity in environmentally similar basins. A relationship has been identified between the Atlantic Multidecadal Variation and erosivity patterns, suggesting a role of North Atlantic circulation dynamics on the hydrology of central Italy’s fluvial basins.
On the Nature of Quality in the Contexts of Academic Publication and Sustainability
Authors: Shephard Kerry , Thondhlana Gladman , Wolff Lili-Ann , Belluigi Dina Zoe , Rieckmann Marco , Vega-Marcote Pedro
Published: April 2021

Six experienced academic reviewers and editors explored the nature of quality in academic publication processes in the contexts of sustainability, education for sustainability and the Sustainable Development Goals (SDGs). This article documents their exploration as a collaborative autoethnography structured around the authors’ personal reflections on matters such as: how current quality indicators define the quality of academic publications; how effective current quality assurance processes may be; how congruent open access publication processes may be with the ideals of sustainability and of the SDGs; and about what new and different indicators of quality might look like. An inductive analysis of their reflections yielded three emergent and reoccurring themes: casting doubt on the fitness for purpose of current academic publication processes and means to assure their quality; seeking justice for all involved in academic publication; and creating opportunities for change. In writing this article, authors considered these themes and how academia might address them.
Tenors Not Sopranos: Bio-Mechanical Constraints on Calling Song Frequencies in the Mediterranean Field-Cricket
Authors: Jonsson Thorin , Montealegre-Z Fernando , Soulsbury Carl D. , Robert Daniel
Published: April 2021

Male crickets and their close relatives bush-crickets (Gryllidae and Tettigoniidae, respectively; Orthoptera and Ensifera) attract distant females by producing loud calling songs. In both families, sound is produced by stridulation, the rubbing together of their forewings, whereby the plectrum of one wing is rapidly passed over a serrated file on the opposite wing. The resulting oscillations are amplified by resonating wing regions. A striking difference between Gryllids and Tettigoniids lies in wing morphology and composition of song frequency: Crickets produce mostly low-frequency (2–8 kHz), pure tone signals with highly bilaterally symmetric wings, while bush-crickets use asymmetric wings for high-frequency (10–150 kHz) calls. The evolutionary reasons for this acoustic divergence are unknown. Here, we study the wings of actively stridulating male field-crickets (Gryllus bimaculatus) and present vibro-acoustic data suggesting a biophysical restriction to low-frequency song. Using laser Doppler vibrometry (LDV) and brain-injections of the neuroactivator eserine to elicit singing, we recorded the topography of wing vibrations during active sound production. In freely vibrating wings, each wing region resonated differently. When wings coupled during stridulation, these differences vanished and all wing regions resonated at an identical frequency, that of the narrow-band song (∼5 kHz). However, imperfections in wing-coupling caused phase shifts between both resonators, introducing destructive interference with increasing phase differences. The effect of destructive interference (amplitude reduction) was observed to be minimal at the typical low frequency calls of crickets, and by maintaining the vibration phase difference below 80°. We show that, with the imperfect coupling observed, cricket song production with two symmetric resonators becomes acoustically inefficient above ∼8 kHz. This evidence reveals a bio-mechanical constraint on the production of high-frequency song whilst using two coupled resonators and provides an explanation as to why crickets, unlike bush-crickets, have not evolved to exploit ultrasonic calling songs.
Soluble BTN2A1 Is a Potential Prognosis Biomarker in Pre-Treated Advanced Renal Cell Carcinoma
Authors: Billon Emilien , Chanez Brice , Rochigneux Philippe , Albiges Laurence , Vicier Cécile , Pignot Géraldine , Walz Jochen , Chretien Anne-Sophie , Gravis Gwenaelle , Olive Daniel
Published: April 2021

The development of immune checkpoint inhibitors (ICI) has dramatically changed the landscape of therapies for metastatic renal cell carcinoma. However, many patients do not benefit from such therapy and prognostic or predictive validated biomarker validated for ICI are still needed to better select and treat patient. Plasmatic soluble immune checkpoints have been described as potential immune biomarkers in hematological malignancies and solids tumors, then, we would like to explore the prognostic value of different soluble immune checkpoints in patients with mRCC treated with nivolumab after TKI. We prospectively collected plasma samples before nivolumab infusion from 38 patients previously treated for mRCC with TKI at Paoli-Calmettes Institute, from the NIVOREN GETUG-AFU 26 study (NCT03013335). Enzyme-linked immunosorbent assays (ELISA) were performed for soluble forms of PD-1, PD-L1, global BTN3, BTLA, BTN3A1 and BTN2A1. Among the different soluble checkpoints analyzed, only high baseline plasmatic level of BTN2A1 was significantly associated with shorter PFS: median PFS was 3.95 months for sBTN2A1high vs 14.30 months for sBTN2A1low (sBTN2A1 cut-off: 6.7ng/mL; HR = 2.26, 95%CI [0.68 – 4.60], p = 0.0307). There was no statistical difference in OS between sBTN2A1high and sBTN2A1low. Our results suggest that the baseline level of plasmatic BTN2A1 could be an independent prognosis factor of PFS after nivolumab for pre-treated patient with mRCC. However, these results need to be validated in a larger prospective cohort and the biological role of BTN subfamily and γδ T cell immunity in mRCC must be elucidated.
Study on the Properties and Mechanisms of a Cement-Stabilized Aggregate Mixture With Vibration Mixing
Authors: Li Ping , Wei Di , Zhang Dongmei , Xiong Jianping , Xu Sheng
Published: April 2021

In order to understand the influence of the vibration mixing method on the performance of cement-stabilized aggregate mixture (CSAM), in this study, an unconfined compressive strength test, drying shrinkage test and the influence of gradation characteristics on compressive strength were used to systematically analyze the performance of CSAM based on vibration mixing. At the same time, the influence mechanism of vibration mixing on the interface transition zone of cement aggregate was analyzed by use of a scanning electron microscope (SEM), and the influence of the mixing method on cement dispersion uniformity was studied by the ethylene diamine tetraacetic acid (EDTA) titration method. The results show that 7 days of unconfined compressive strength and crack resistance of the CSAM with vibration mixing is better than those of the ordinary mixing, and the aggregate grade has a great influence on the compressive strength of the CSAM. Vibration mixing can improve the micro-water-cement ratio uniformity of CSAM and significantly improve the bonding condition of the interface transition zone between cement paste and aggregate, thus enhancing the structural compactness of CSAM. The dispersion uniformity of cement under the vibration mixing is better than that of ordinary mixing.
One-Year Adherence to Continuous Positive Airway Pressure With Telemonitoring in Sleep Apnea Hypopnea Syndrome: A Randomized Controlled Trial
Authors: Contal Olivier , Poncin William , Vaudan Stéphanie , De Lys Angélique , Takahashi Hiromitsu , Bochet Séverine , Grandin Stéphane , Kehrer Philippe , Charbonnier Florian
Published: April 2021

Study Objective: Telemedicine (TM) for continuous positive airway pressure (CPAP) treated patients may save health-care resources without compromising treatment effectiveness. We assessed the effect of TM (AirView Online System, ResMed) during the CPAP habituation phase on 3-month and 1-year treatment adherence and efficacy in patients with moderate-to-severe obstructive sleep apnea (OSA).

Methods: At CPAP initiation, 120 patients diagnosed with OSA were randomized to either usual care (UC) or TM during the habituation phase (clinical registration: ISRCTN12865936). Both groups received a first face-to-face appointment with a sleep care giver at CPAP initiation. Within the following month, 2 other physical visits were scheduled in the UC group whereas two phone consultations were planned in the TM group, in which CPAP parameters were remotely adapted. Additional physical visits were programmed at the patient's request. Face-to-face consultations were scheduled at 3 and 12 months after CPAP initiation. The primary outcome was the mean CPAP daily use over the course of 12 months.

Results: Twenty of 60 patients stopped CPAP therapy in the UC group vs. 14 of 60 in the TM group (p = 0.24). In per protocol analysis, mean [95% CI] daily CPAP use among 86 patients still using CPAP at 12 months was 279 [237; 321] min in the 38 patients on UC and 279 [247; 311] min in the 43 patients on TM, mean difference [95% CI]: 0 [−52; 52] min, P = 0.99. Total consultation time per patient was not different between groups, TM: 163 [147; 178] min, UC: 178 [159; 197] min, difference: −15 [−39; 9] min, p = 0.22.

Conclusions: Telemedicine during the CPAP habituation phase did not alter daily CPAP use or treatment adherence and did not require more healthcare time. Telemedicine may support clinic attendance for CPAP titration.

Clinical Trial Registration: [ISRCTN], identifier [ISRCTN12865936].
Metabolic Alterations in Shrimp Stomach During Acute Hepatopancreatic Necrosis Disease and Effects of Taurocholate on Vibrio parahaemolyticus
Authors: Kumar Ramya , Tung Teng-Chun , Ng Tze Hann , Chang Che-Chih , Chen Yi-Lun , Chen Yi-Min , Lin Shih-Shun , Wang Han-Ching
Published: April 2021

Acute hepatopancreatic necrosis disease (AHPND), a recently emerged bacterial shrimp disease, has increased shrimp mortality and caused huge economic losses in many Asian countries. However, molecular factors underlying pathogenesis of this disease remain largely unknown. Our objective was to characterize metabolic alterations in shrimp stomach during AHPND and determine effects of taurocholate on AHPND-causing Vibrio parahaemolyticus. Based on metabolomics, pathways for lipid metabolism and for primary bile acid (BA) synthesis were majorly affected following AHPND infection. Bile acid metabolites, namely taurocholate, were downregulated in the metabolomics database. This prompted us to study effects of taurocholate on biofilm formation, PirABvp toxin release and biofilm detachment capabilities in AHPND-causing V. parahaemolyticus. Treatment of this bacterium with high concentration of taurocholate, a primary bile acid, induced biofilm formation, PirABvp toxin release and facilitated the dispersion of bacterial cells. Taken together, our findings suggest that AHPND infection can affect the lipid metabolites in shrimp stomach, and further suggest that the primary bile acid taurocholate is important for the virulence of AHPND-causing V. parahaemolyticus.
Bioaugmented Phytoremediation of Metal-Contaminated Soils and Sediments by Hemp and Giant Reed
Authors: Ferrarini Andrea , Fracasso Alessandra , Spini Giulia , Fornasier Flavio , Taskin Eren , Fontanella Maria Chiara , Beone Gian Maria , Amaducci Stefano , Puglisi Edoardo
Published: April 2021

We assessed the effects of EDTA and selected plant growth-promoting rhizobacteria (PGPR) on the phytoremediation of soils and sediments historically contaminated by Cr, Ni, and Cu. A total of 42 bacterial strains resistant to these heavy metals (HMs) were isolated and screened for PGP traits and metal bioaccumulation, and two Enterobacter spp. strains were finally selected. Phytoremediation pot experiments of 2 months duration were carried out with hemp (Cannabis sativa L.) and giant reed (Arundo donax L.) grown on soils and sediments respectively, comparing in both cases the effects of bioaugmentation with a single PGPR and EDTA addition on plant and root growth, plant HM uptake, HM leaching, as well as the changes that occurred in soil microbial communities (structure, biomass, and activity). Good removal percentages on a dry mass basis of Cr (0.4%), Ni (0.6%), and Cu (0.9%) were observed in giant reed while negligible values (<100‰) in hemp. In giant reed, HMs accumulated differentially in plant (rhizomes > > roots > leaves > stems) with largest quantities in rhizomes (Cr 0.6, Ni 3.7, and Cu 2.2 g plant–1). EDTA increased Ni and Cu translocation to aerial parts in both crops, despite that in sediments high HM concentrations in leachates were measured. PGPR did not impact fine root diameter distribution of both crops compared with control while EDTA negatively affected root diameter class length (DCL) distribution. Under HM contamination, giant reed roots become shorter (from 5.2 to 2.3 mm cm–3) while hemp roots become shorter and thickened from 0.13 to 0.26 mm. A consistent indirect effect of HM levels on the soil microbiome (diversity and activity) mediated by plant response (root DCL distribution) was observed. Multivariate analysis of bacterial diversity and activity revealed not only significant effects of plant and soil type (rhizosphere vs. bulk) but also a clear and similar differentiation of communities between control, EDTA, and PGPR treatments. We propose root DCL distribution as a key plant trait to understand detrimental effect of HMs on microbial communities. Positive evidence of the soil-microbe-plant interactions occurring when bioaugmentation with PGPR is associated with deep-rooting perennial crops makes this combination preferable over the one with chelating agents. Such knowledge might help to yield better bioaugmented bioremediation results in contaminated sites.
Exploring Trait Trade-Offs for Fungal Decomposers in a Southern California Grassland
Authors: Alster Charlotte J. , Allison Steven D. , Glassman Sydney I. , Martiny Adam C. , Treseder Kathleen K.
Published: April 2021

Fungi are important decomposers in terrestrial ecosystems, so their responses to climate change might influence carbon (C) and nitrogen (N) dynamics. We investigated whether growth and activity of fungi under drought conditions were structured by trade-offs among traits in 15 fungal isolates from a Mediterranean Southern California grassland. We inoculated fungi onto sterilized litter that was incubated at three moisture levels (4, 27, and 50% water holding capacity, WHC). For each isolate, we characterized traits that described three potential lifestyles within the newly proposed “YAS” framework: growth yield, resource acquisition, and stress tolerance. Specifically, we measured fungal hyphal length per unit litter decomposition for growth yield; the potential activities of the extracellular enzymes cellobiohydrolase (CBH), β-glucosidase (BG), β-xylosidase (BX), and N-acetyl-β-D-glucosaminidase (NAG) for resource acquisition; and ability to grow in drought vs. higher moisture levels for drought stress tolerance. Although, we had hypothesized that evolutionary and physiological trade-offs would elicit negative relationships among traits, we found no supporting evidence for this hypothesis. Across isolates, growth yield, drought stress tolerance, and extracellular enzyme activities were not significantly related to each other. Thus, it is possible that drought-induced shifts in fungal community composition may not necessarily lead to changes in fungal biomass or decomposer ability in this arid grassland.
Brazilian Artisanal Cheeses: Diversity, Microbiological Safety, and Challenges for the Sector
Authors: Pineda Ana Paulina Arellano , Campos Gabriela Zampieri , Pimentel-Filho Natan Jesus , Franco Bernadette Dora Gombossy de Melo , Pinto Uelinton Manoel
Published: April 2021

Artisanal cheeses made with raw milk are highly appreciated products in Brazil. Most of these cheeses are produced in small facilities across different production regions in the country, some of which have been granted a protected designation of origin and are award winners. The most prominent state that manufactures these products is Minas Gerais (MG), but production is also gaining strength in other Brazilian states. The major challenge faced by artisanal cheese production is related to microbial risks associated with foodborne pathogens when the quality of the raw milk is unsatisfactory. Regulations created for the dairy industry are constantly been revised and adapted, considering the small-scale production of Brazilian artisanal cheeses, in order to guarantee safety at all steps of cheese production and commercialization. This text presents a summary of the huge diversity of artisanal cheeses produced in the country, grouped by geographical regions, and reviews the current challenges faced by producers and government considering the safety of these cheeses.
Identification of mRNA-, circRNA- and lncRNA- Associated ceRNA Networks and Potential Biomarkers for Preeclampsia From Umbilical Vein Endothelial Cells
Authors: Chen Dan , He Biwei , Zheng Panchan , Wang Shuying , Zhao Xueya , Liu Jinyu , Yang Xingyu , Cheng Weiwei
Published: April 2021

Objective

The etiology and pathogenesis of preeclampsia (PE) remain unclear, and ideal biomarkers for the early detection of PE are scarce. The involvement of the competing endogenous RNA (ceRNA) hypothesis in PE is only partially understood. The present study aimed to delineate a regulatory network in PE comprised of messenger RNAs (mRNAs), circular RNAs (circRNAs), long non-coding RNAs (lncRNAs), and microRNAs (miRNAs) via ceRNA profiles from human umbilical vein endothelial cells (HUVECs) to further reveal the pathogenesis of PE and potential biomarkers.

Methods

Differentially expressed mRNAs, circRNAs, and lncRNAs were detected in HUVECs from early onset preeclampsia (EOPE) cases (n= 4) and normal pregnancies (n= 4) by microarray analysis. Bioinformatics analysis was performed to systematically analyze the data, and a relevant ceRNA network was constructed. RNAs (ANGPT2,LIPG,hsa_circ_0025992,hsa_circ_0090396,hsa_circ_0066955,hsa_circ_0041203,hsa_circ_0018116,lnc-C17orf64-1:1,lnc-SLC27A2-2:1, andlnc-UEVLD-5:1) were validated by quantitative real-time PCR (qRT-PCR) in 10 pairs of HUVECs and placental tissues from PE patients and normal pregnancies. Furthermore, expression ofhsa_circ_0025992was detected in maternal peripheral blood samples from PE patients (n= 24) and normal pregnancies (n= 30) to confirm its potential as a novel biomarker. The receiver operating characteristic (ROC) curve was applied to analyze its diagnostic value.

Results

Compared with HUVECs from normal pregnancies, HUVECs from EOPE cases had 33 differentially expressed mRNAs (DEmRNAs), 272 DEcircRNAs, and 207 DElncRNAs. GO and KEGG analyses of the DERNAs revealed the biological processes and pathways involved in PE. Based on the microarray data and the predicted miRNAs, a ceRNA network was constructed with four mRNAs, 34 circRNAs, nine lncRNAs, and 99 miRNAs. GO and KEGG analyses of the network reinforced the crucial roles of metabolic disorders, the p53 and JAK/STAT signaling pathways in PE. In addition, ROC analysis indicated thathsa_circ_0025992could be used as a novel biomarker for PE.

Conclusion

A novel ceRNA network was revealed in PE, and the potential ofhsa_circ_0025992to serve as a new biomarker was confirmed.
Being the Family Caregiver of a Patient With Dementia During the Coronavirus Disease 2019 Lockdown
Authors: Zucca Milena , Isella Valeria , Lorenzo Raffaele Di , Marra Camillo , Cagnin Annachiara , Cupidi Chiara , Bonanni Laura , Laganà Valentina , Rubino Elisa , Vanacore Nicola , Agosta Federica , Caffarra Paolo , Sambati Renato , Quaranta Davide , Guglielmi Valeria , Appollonio Ildebrando M. , Logroscino Giancarlo , Filippi Massimo , Tedeschi Gioacchino , Ferrarese Carlo , Rainero Innocenzo , Bruni Amalia C. ,   the SINdem COVID-19 Study Group
Published: April 2021

Background: Family caregivers of patients with dementia are at high risk of stress and burden, and quarantine due to the coronavirus disease 2019 (COVID-19) pandemic may have increased the risk of psychological disturbances in this population. The current study was carried out during the national lockdown declared in March 2020 by the Italian government as a containment measure of the first wave of the coronavirus pandemic and is the first nationwide survey on the impact of COVID-19 lockdown on the mental health of dementia informal caregivers.

Methods: Eighty-seven dementia centers evenly distributed on the Italian territory enrolled 4,710 caregiver–patient pairs. Caregivers underwent a telephone interview assessing classical symptoms of caregiver stress and concern for the consequences of COVID-19 infection on patient’s health. We calculated prevalence of symptoms and regressed them on various potential stress risk factors: caregivers’ sociodemographic characteristics and lifestyle, patients’ clinical features, and lockdown-related elements, like discontinuity in medical care.

Results: Approximately 90% of caregivers reported at least one symptom of stress, and nearly 30% reported four or more symptoms. The most prevalent symptoms were concern for consequences of COVID-19 on patient’s health (75%) and anxiety (46%). The main risk factors for stress were identified as a conflicting relationship with the patient and discontinuity in assistance, but caregiver’s female sex, younger age, lower education, and cohabitation with the patient also had an impact. Availability of help from institutions or private individuals showed a protective effect against sense of abandonment but a detrimental effect on concern about the risk for the patient to contract COVID-19. The only protective factor was mild dementia severity, which was associated with a lower risk of feeling isolated and abandoned; type of dementia, on the other hand, did not affect stress risk.

Conclusion: Our results demonstrate the large prevalence of stress in family caregivers of patients with dementia during the COVID-19 pandemic and have identified both caregivers and situations at a higher risk of stress, which should be taken into account in the planning of interventions in support of quarantined families and patients.
Case Report: Histiocytic Necrotizing Lymphadenitis (Kikuchi–Fujimoto Disease) Concurrent With Aseptic Meningitis
Authors: Song Yanna , Liu Shan , Song Lei , Chen Huaqiu , Bai Miaoshui , Yan Jinhua , Luo Tianfei , Liu Kangding , Sun Li , Zhao Yang
Published: April 2021

Kikuchi–Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis, is a rare, benign, self-limiting disease characterized by local lymphadenopathy. Central nervous system involvement in KFD is extremely rare and remains a diagnostic challenge. Only 41 cases of aseptic meningitis associated with KFD have been reported worldwide, with just four cases (including our case) of KFD with meningitis as the first symptom. We report a case of KFD accompanied by aseptic meningitis with severely high intracranial pressure (400 mmH2O), increased white blood cell count (56 × 106/L), and moderately elevated protein level (0.52 g/L). This case is unique in the delayed appearance of lymphadenopathy. After 1 month of treatment with steroids, fever, headache, and lymphadenopathy gradually disappeared, and the result of cerebrospinal fluid examination gradually became normal. In conclusion, based on our case findings and our literature review on KFD with aseptic meningitis, a diagnosis of KFD should be considered when delayed appearance of lymphadenopathy is observed in patients with aseptic meningitis.
Pathophysiological Bases of Comorbidity in Migraine
Authors: Altamura Claudia , Corbelli Ilenia , de Tommaso Marina , Di Lorenzo Cherubino , Di Lorenzo Giorgio , Di Renzo Antonio , Filippi Massimo , Jannini Tommaso B. , Messina Roberta , Parisi Pasquale , Parisi Vincenzo , Pierelli Francesco , Rainero Innocenzo , Raucci Umberto , Rubino Elisa , Sarchielli Paola , Li Linxin , Vernieri Fabrizio , Vollono Catello , Coppola Gianluca
Published: April 2021

Despite that it is commonly accepted that migraine is a disorder of the nervous system with a prominent genetic basis, it is comorbid with a plethora of medical conditions. Several studies have found bidirectional comorbidity between migraine and different disorders including neurological, psychiatric, cardio- and cerebrovascular, gastrointestinal, metaboloendocrine, and immunological conditions. Each of these has its own genetic load and shares some common characteristics with migraine. The bidirectional mechanisms that are likely to underlie this extensive comorbidity between migraine and other diseases are manifold. Comorbid pathologies can induce and promote thalamocortical network dysexcitability, multi-organ transient or persistent pro-inflammatory state, and disproportionate energetic needs in a variable combination, which in turn may be causative mechanisms of the activation of an ample defensive system with includes the trigeminovascular system in conjunction with the neuroendocrine hypothalamic system. This strategy is designed to maintain brain homeostasis by regulating homeostatic needs, such as normal subcortico-cortical excitability, energy balance, osmoregulation, and emotional response. In this light, the treatment of migraine should always involves a multidisciplinary approach, aimed at identifying and, if necessary, eliminating possible risk and comorbidity factors.
High Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols (FODMAP) Consumption Among Endurance Athletes and Relationship to Gastrointestinal Symptoms
Authors: Killian Lauren A. , Muir Jane G. , Barrett Jacqueline S. , Burd Nicholas A. , Lee Soo-Yeun
Published: April 2021

Endurance athletes commonly experience lower gastrointestinal (GI) symptoms similar to those of irritable bowel syndrome (IBS). Previous research on the restriction of fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP), a diet-based mitigation strategy initially developed for IBS, has shown promise for application in athlete populations. Athlete's dietary strategies surrounding exercise have not been formally assessed in relation to FODMAP content of foods or sports nutrition products. Additionally, the FODMAP content of athlete's habitual diets has not been examined in larger sample sizes. This research aims to investigate the FODMAP content of endurance athlete diets by examining these three areas, in conjunction with GI symptoms. Dietary habits surrounding exercise and GI symptoms were examined in 430 endurance athletes using a previously validated Endurance Athlete Questionnaire. A subset of athletes (n = 73) completed a FODMAP-specific food frequency questionnaire for habitual intake. The most commonly reported sports nutrition products were analyzed for FODMAP content using standardized analytical methods. Mean habitual intakes were compared to previous FODMAP studies and medians were compared between those with and without lower GI symptoms. Athletes commonly consumed high FODMAP foods during pre-race dinners and breakfasts, with over 60% reporting specific high FODMAP foods. More frequent nutrition product use, particularly solid, gel/gummy, and homemade products, was often related to increased frequency of GI symptoms. Of the sixteen commonly used sports nutrition products tested, seven were high FODMAP in one serving. All but one of the remaining products became high FODMAP when consumed in multiple servings, as is likely the case during endurance exercise. Average habitual FODMAP intake was 26.1 g (±15.9 g), similar to intakes classified as high FODMAP in previous research on FODMAPs and IBS or GI symptoms. Only 15.1% of athletes consumed a diet that would be considered low in FODMAP. Exploratory analyses showed higher intake of some FODMAP types among athletes exhibiting various lower GI symptoms. Overall, this study demonstrated that FODMAP intake by endurance athletes is high both surrounding exercise and habitually, and may be contributing to GI symptoms experienced during exercise. This information can be utilized when analyzing athlete diets and selecting foods to decrease GI symptoms.
GEO Data Mining Identifies OLR1 as a Potential Biomarker in NSCLC Immunotherapy
Authors: Liu Bin , Wang Ziyu , Gu Meng , Zhao Cong , Ma Teng , Wang Jinghui
Published: April 2021

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. The tumor immune microenvironment (TME) in NSCLC is closely correlated to tumor initiation, progression, and prognosis. TME failure impedes the generation of an effective antitumor immune response. In this study, we attempted to explore TME and identify a potential biomarker for NSCLC immunotherapy. 48 potential immune-related genes were identified from 11 eligible Gene Expression Omnibus (GEO) data sets. We applied the CIBERSORT computational approach to quantify bulk gene expression profiles and thereby infer the proportions of 22 subsets of tumor-infiltrating immune cells (TICs); 16 kinds of TICs showed differential distributions between the tumor and control tissue samples. Multiple linear regression analysis was used to determine the correlation between TICs and 48 potential immune-related genes. Nine differential immune-related genes showed statistical significance. We analyzed the influence of nine differential immune-related genes on NSCLC immunotherapy, and OLR1 exhibited the strongest correlation with four well-recognized biomarkers (PD-L1, CD8A, GZMB, and NOS2) of immunotherapy. Differential expression of OLR1 showed its considerable potential to divide TICs distribution, as determined by non-linear dimensionality reduction analysis. In immunotherapy prediction analysis with the comparatively reliable tool TIDE, patients with higher OLR1 expression were predicted to have better immunotherapy outcomes, and OLR1 expression was potentially highly correlated with PD-L1 expression, the average of CD8A and CD8B, IFNG, and Merck18 expression, T cell dysfunction and exclusion potential, and other significant immunotherapy predictors. These findings contribute to the current understanding of TME with immunotherapy. OLR1 also shows potential as a predictor or a regulator in NSCLC immunotherapy.