bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metformin attenuates hypothalamic inflammation via downregulation of RIPK1-independent microglial necroptosis in diet-induced obese mice
Authors: Li Xuan , Cai You , Luo Jiao , Ding Jingyun , Yao Guojun , Xiao Xiaohua , Tang Yizhe , Liang Zhen 
Published: November 2021

AbstractNecroptosis, a form of programmed cell death, accounts for many inflammations in a wide range of diseases. Diet-induced obesity is manifested by low-grade inflammation in the mediobasal hypothalamus (MBH), and microglia are implicated as critical responsive components for this process. Here, we demonstrate that microglial necroptosis plays a pivotal role in obesity-related hypothalamic inflammation, facilitating proinflammatory cytokine production, such as TNF-α and IL-1β. Treatment with the anti-diabetic drug metformin effectively reduces the obese phenotypes in the high-fat diet (HFD)-fed mice, attributing to remission of hypothalamic inflammation partly through repressing microglial necroptosis. Importantly, using the receptor-interacting protein kinase 1 inhibitor, necrostatin-1s, could not suppress the microglial inflammation nor prevent body weight gain in the obese mice, indicating that the microglial necroptosis is RIPK1-independent. Altogether, these findings offer new insights into hypothalamic inflammation in diet-induced obesity and provide a novel mechanism of action for metformin in obesity treatment.
Combining callers improves the detection of copy number variants from whole-genome sequencing
Authors: Coutelier Marie , Holtgrewe Manuel , Jäger Marten , Flöttman Ricarda , Mensah Martin A. , Spielmann Malte , Krawitz Peter , Horn Denise , Beule Dieter , Mundlos Stefan 
Published: November 2021

AbstractCopy Number Variants (CNVs) are deletions, duplications or insertions larger than 50 base pairs. They account for a large percentage of the normal genome variation and play major roles in human pathology. While array-based approaches have long been used to detect them in clinical practice, whole-genome sequencing (WGS) bears the promise to allow concomitant exploration of CNVs and smaller variants. However, accurately calling CNVs from WGS remains a difficult computational task, for which a consensus is still lacking. In this paper, we explore practical calling options to reach the best compromise between sensitivity and sensibility. We show that callers based on different signal (paired-end reads, split reads, coverage depth) yield complementary results. We suggest approaches combining four selected callers (Manta, Delly, ERDS, CNVnator) and a regenotyping tool (SV2), and show that this is applicable in everyday practice in terms of computation time and further interpretation. We demonstrate the superiority of these approaches over array-based Comparative Genomic Hybridization (aCGH), specifically regarding the lack of resolution in breakpoint definition and the detection of potentially relevant CNVs. Finally, we confirm our results on the NA12878 benchmark genome, as well as one clinically validated sample. In conclusion, we suggest that WGS constitutes a timely and economically valid alternative to the combination of aCGH and whole-exome sequencing.
The effect of systemic levels of TNF-alpha and complement pathway activity on outcomes of VEGF inhibition in neovascular AMD
Authors: Khan Adnan H. , Pierce Charles O. , De Salvo Gabriella , Griffiths Helen , Nelson Marie , Cree Angela J. , Menon Geeta , Lotery Andrew J. 
Published: November 2021

Abstract
Background/Objectives
Systemic levels of pro-inflammatory cytokines and activated complement components affect the risk and/or progression of neovascular age-related macular degeneration (AMD). This study investigated the effect of serum pro-inflammatory cytokine levels and complement pathway activity on the clinical response to vascular endothelial growth factor (VEGF) inhibition in neovascular AMD.

Methods
Sixty-five patients with a new diagnosis of neovascular AMD were observed over a six-month period in a single-centre, longitudinal cohort study. At each visit, the visual acuity score (VAS), central macular thickness (CMT), serum levels of CRP, pro-inflammatory cytokines (TNF-α, IL-1β, IL-2, IL-6 and IL-8), and complement pathway activity were measured. Participant DNA samples were sequenced for six complement pathway single nucleotide polymorphisms (SNPs) associated with AMD.

Results
A statistically significant difference in VAS was observed for serum levels of TNF-α only: there was a gain in VAS (from baseline) of 1.37 for participants below the 1st quartile of mean concentration compared to a reduction of 2.71 for those above the 3rd quartile. Statistical significance was maintained after Bonferroni correction (P value set at <0.006). No significant differences in CMT were observed. In addition, statistically significant differences, maintained after Bonferroni correction, were observed in serum complement activity for participants with the following SNPs: CFH region (rs1061170), SERPING1 (rs2511989) and CFB (rs641153). Serum complement pathway components did not significantly affect VAS.

Conclusions
Lower serum TNF-α levels were associated with an increase in visual acuity after anti-VEGF therapy. This suggests that targeting pro-inflammatory cytokines may augment treatment for neovascular AMD.
Deficiency of TET3 leads to a genome-wide DNA hypermethylation episignature in human whole blood
Authors: Levy Michael A. , Beck David B. , Metcalfe Kay , Douzgou Sofia , Sithambaram Sivagamy , Cottrell Trudie , Ansar Muhammad , Kerkhof Jennifer , Mignot Cyril , Nougues Marie-Christine , Keren Boris , Moore Hannah W. , Oegema Renske , Giltay Jacques C. , Simon Marleen , van Jaarsveld Richard H. , Bos Jessica , van Haelst Mieke , Motazacker M. Mahdi , Boon Elles M. J. , Santen Gijs W. E. , Ruivenkamp Claudia A. L. , Alders Marielle , Luperchio Teresa Romeo , Boukas Leandros , Ramsey Keri , Narayanan Vinodh , Schaefer G. Bradley , Bonasio Roberto , Doheny Kimberly F. , Stevenson Roger E. , Banka Siddharth , Sadikovic Bekim , Fahrner Jill A. 
Published: November 2021

AbstractTET3 encodes an essential dioxygenase involved in epigenetic regulation through DNA demethylation. TET3 deficiency, or Beck-Fahrner syndrome (BEFAHRS; MIM: 618798), is a recently described neurodevelopmental disorder of the DNA demethylation machinery with a nonspecific phenotype resembling other chromatin-modifying disorders, but inconsistent variant types and inheritance patterns pose diagnostic challenges. Given TET3’s direct role in regulating 5-methylcytosine and recent identification of syndrome-specific DNA methylation profiles, we analyzed genome-wide DNA methylation in whole blood of TET3-deficient individuals and identified an episignature that distinguishes affected and unaffected individuals and those with mono-allelic and bi-allelic pathogenic variants. Validation and testing of the episignature correctly categorized known TET3 variants and determined pathogenicity of variants of uncertain significance. Clinical utility was demonstrated when the episignature alone identified an affected individual from over 1000 undiagnosed cases and was confirmed upon distinguishing TET3-deficient individuals from those with 46 other disorders. The TET3-deficient signature - and the signature resulting from activating mutations in DNMT1 which normally opposes TET3 - are characterized by hypermethylation, which for BEFAHRS involves CpG sites that may be biologically relevant. This work expands the role of epi-phenotyping in molecular diagnosis and reveals genome-wide DNA methylation profiling as a quantitative, functional readout for characterization of this new biochemical category of disease.
Beyond the standard quantum limit for parametric amplification of broadband signals
Authors: Renger M. , Pogorzalek S. , Chen Q. , Nojiri Y. , Inomata K. , Nakamura Y. , Partanen M. , Marx A. , Gross R. , Deppe F. , Fedorov K. G. 
Published: November 2021

AbstractThe low-noise amplification of weak microwave signals is crucial for countless protocols in quantum information processing. Quantum mechanics sets an ultimate lower limit of half a photon to the added input noise for phase-preserving amplification of narrowband signals, also known as the standard quantum limit (SQL). This limit, which is equivalent to a maximum quantum efficiency of 0.5, can be overcome by employing nondegenerate parametric amplification of broadband signals. We show that, in principle, a maximum quantum efficiency of unity can be reached. Experimentally, we find a quantum efficiency of 0.69 ± 0.02, well beyond the SQL, by employing a flux-driven Josephson parametric amplifier and broadband thermal signals. We expect that our results allow for fundamental improvements in the detection of ultraweak microwave signals.
Room temperature XFEL crystallography reveals asymmetry in the vicinity of the two phylloquinones in photosystem I
Authors: Keable Stephen M. , Kölsch Adrian , Simon Philipp S. , Dasgupta Medhanjali , Chatterjee Ruchira , Subramanian Senthil Kumar , Hussein Rana , Ibrahim Mohamed , Kim In-Sik , Bogacz Isabel , Makita Hiroki , Pham Cindy C. , Fuller Franklin D. , Gul Sheraz , Paley Daniel , Lassalle Louise , Sutherlin Kyle D. , Bhowmick Asmit , Moriarty Nigel W. , Young Iris D. , Blaschke Johannes P. , de Lichtenberg Casper , Chernev Petko , Cheah Mun Hon , Park Sehan , Park Gisu , Kim Jangwoo , Lee Sang Jae , Park Jaehyun , Tono Kensuke , Owada Shigeki , Hunter Mark S. , Batyuk Alexander , Oggenfuss Roland , Sander Mathias , Zerdane Serhane , Ozerov Dmitry , Nass Karol , Lemke Henrik , Mankowsky Roman , Brewster Aaron S. , Messinger Johannes , Sauter Nicholas K. , Yachandra Vittal K. , Yano Junko , Zouni Athina , Kern Jan 
Published: November 2021

AbstractPhotosystem I (PS I) has a symmetric structure with two highly similar branches of pigments at the center that are involved in electron transfer, but shows very different efficiency along the two branches. We have determined the structure of cyanobacterial PS I at room temperature (RT) using femtosecond X-ray pulses from an X-ray free electron laser (XFEL) that shows a clear expansion of the entire protein complex in the direction of the membrane plane, when compared to previous cryogenic structures. This trend was observed by complementary datasets taken at multiple XFEL beamlines. In the RT structure of PS I, we also observe conformational differences between the two branches in the reaction center around the secondary electron acceptors A1A and A1B. The π-stacked Phe residues are rotated with a more parallel orientation in the A-branch and an almost perpendicular confirmation in the B-branch, and the symmetry breaking PsaB-Trp673 is tilted and further away from A1A. These changes increase the asymmetry between the branches and may provide insights into the preferential directionality of electron transfer.
Subjective well-being in non-obese individuals depends strongly on body composition
Authors: Chlabicz Małgorzata , Dubatówka Marlena , Jamiołkowski Jacek , Sowa Paweł , Łapińska Magda , Raczkowski Andrzej , Łaguna Wojciech , Moniuszko-Malinowska Anna M. , Waszkiewicz Napoleon , Kowalska Irina , Kamiński Karol A. 
Published: November 2021

AbstractWhile obesity has been correlated with welfare in the general population, there is not much data on the influence of body composition on welfare among the non-obese adult individuals. In this study, a total of 726 non-obese individuals from the general population were analyzed. The mean age was 46.8 ± 15.4 years and 42.1% of participants were male. The anthropometric measurements and dual energy X-ray absorptiometry (DEXA) were done. The mean value for the Satisfaction with Life Scale (SWLS) was 23.09 ± 5.43, for Euro Quality of Life Visual Analogue Scale (EQ-VAS) was 78.0 ± 14.5, and for the Beck Depression Inventory (BDI) was 6.7 ± 6.6. On the SWLS, the higher waist-hip ratio had a negative impact even after adjusting for age, gender, and concomitant diseases. EQ-VAS was inversely associated with android fat distribution and directly associated with muscle mass. BDI value was inversely associated with lower muscle mass, especially in lower limbs. The well-being of women was mainly associated with the distribution of adipose tissue and less with the distribution of muscle tissue—abdominal fat distribution has a particularly negative impact on well-being among women. In contrast, men’s well-being depends more on muscle mass and to a lesser extent on the distribution of fat tissue—a positive significant effect has lean mass and a circumference of thigh below gluteal fold.
Unraveling genetics of semi-determinacy and identification of markers for indeterminate stem growth habit in chickpea (Cicer arietinum L.)
Authors: Ambika  , Hegde Venkatraman , Nimmy M. S. , Bharadwaj C. , Tripathi Shailesh , Singh Rajesh Kumar , Kumar Rajendra 
Published: November 2021

AbstractChickpea (Cicer arietinum L.) is predominantly an indeterminate plant and tends to generate vegetative growth when the ambient is conducive for soil moisture, temperature and certain other environmental conditions. The semi-determinate (SDT) types are comparatively early, resistant to lodging and found to be similar in their yield potential to indeterminate (IDT) lines. Indeterminate and semi-determinate genotypes are found to be similar during early stage, which makes it difficult to distinguish between them. Thus, there is a need to identify molecular markers linked either to indeterminate or semi-determinate plant types. The present study was carried out to study the genetics of semi-determinacy and identify molecular markers linked to stem growth habit. The study was undertaken in the cross involving BG 362(IDT) × BG 3078-1(SDT). All F1 plants were indeterminate, which indicates that indeterminate stem type is dominant over semi-determinate. In further advancement to F2 generation, F2 plants are segregated in the ratio of 3(Indeterminate): 1(Semi-determinate) that indicates that the IDT and SDT parents which are involved in the cross differed for a single gene. The segregation pattern observed in F2 is confirmed in F3 generation. The parental polymorphic survey was undertaken for molecular analysis using total of 245 SSR markers, out of which 41 polymorphic markers were found to distinguish the parents and were utilized for bulked segregant analysis (BSA). The segregation pattern in F2 indicates that the IDT (Indeterminate) and SDT (Semi-determinate) parents which are involved in the cross differed for single gene. The segregation pattern of F2 and F3 derived from the cross BG 362 (IDT) × BG 3078-1 (SDT) confirmed the genotypic structure of the newly found SDT genotype BG 3078-1 as dt1dt1Dt2Dt2. Three SSR markers TA42, Ca_GPSSR00560 and H3DO5 were found to be putatively linked to Dt1 locus regulating IDT stem growth habit. Our results indicate that the SSR markers identified for Dt1 locus helps to differentiate stem growth habit of chickpea in its early growth stage itself and can be efficiently utilized in Marker Assisted Selection (MAS) for changed plant type in chickpea.
Validation scheme for solar coronal models: Constraints from multi-perspective observations in EUV and white light
Authors: Wagner A. , Asvestari E. , Temmer M. , Heinemann S. G. , Pomoell J. 
Published: November 2021

Context. In this paper, we present a validation scheme to investigate the quality of coronal magnetic field models, which is based on comparisons with observational data from multiple sources.
Aims. Many of these coronal models may use a range of initial parameters that produce a large number of physically reasonable field configurations. However, that does not mean that these results are reliable and comply with the observations. With an appropriate validation scheme, which is the aim of this work, the quality of a coronal model can be assessed.
Methods. The validation scheme was developed with the example of the EUropean Heliospheric FORecasting Information Asset (EUHFORIA) coronal model. For observational comparison, we used extreme ultraviolet and white-light data to detect coronal features on the surface (open magnetic field areas) and off-limb (streamer and loop) structures from multiple perspectives (Earth view and the Solar Terrestrial Relations Observatory – STEREO). The validation scheme can be applied to any coronal model that produces magnetic field line topology.
Results. We show its applicability by using the validation scheme on a large set of model configurations, which can be efficiently reduced to an ideal set of parameters that matches best with observational data.
Conclusions. We conclude that by using a combined empirical visual classification with a mathematical scheme of topology metrics, a very efficient and objective quality assessment for coronal models can be performed.
Development of a substorms catalog including the MPB observed at Panagjurishte station, Bulgaria
Authors: Guineva Veneta , Werner Rolf , Lubchich Andris , Atanassov Atanas , Bojilova Rumiana , Raykova Lyubomira , Valev Dimitar , Despirak Irina 
Published: November 2021

In this work the first results of the creation of a substorms catalog including the mid-latitude positive bays (MPB) registered at the Bulgarian station Panagjurishte (∼37° GMLat, ∼97° GMLon) are presented. MPB index characterizes the mid-latitude effect of substorm, which developed at auroral latitudes, and it is associated with the substorm current wedge.
The work went in several lines. First, the catalog design and content were taken. Second, tools of data processing have been developed. Third, substorms during two months, namely January and February 2013 were identified. And finally, data processing was implemented and the characteristics of the positive bays were determined.
The obtained data and their visualizations were put in a convenient folder and file structure, ftp positioned.
Facilitated Tenon-Free Conjunctival Autograft Preparation and Limited Tenon Removal Technique in Pterygium Surgery
Authors: Ucar Fikret , Seyrek Lutfi , Cetinkaya Servet , Ture Huseyin , Kadioglu Ekrem 
Published: November 2021

Abstract
Background The main complication of primary pterygium surgery is the recurrence of the pterygium. In the present study, we aimed to compare a classical technique and facilitated tenon-free conjunctival autograft preparation and a limited tenon removal technique in pterygium surgery in terms of recurrence rate, complications, and operation duration.
Material and Methods This is a retrospective, comparative, observational study. Group 1 comprised 120 eyes of 115 patients who underwent pterygium excision with a new facilitated tenon-free conjunctival-limbal autograft preparation and limited tenon removal technique between May 2017 and October 2019. Group 2 comprised 117 eyes of 113 patients who underwent pterygium excision with a conventional conjunctival-limbal autograft technique between January 2016 and May 2017.
Results The mean follow-up time after surgery was 18.2 ± 5.8 months in group 1 and 19.1 ± 6.3 months in group 2 (p = 0.25). The mean operation duration was 5.54 ± 1.22 (4 – 7) minutes in group 1 and 8.23 ± 1.26 (8 – 10) minutes in group 2 (p = 0.02). Flap edema was present in 33 eyes (28.2%) in group 2 and in 11 eyes (9.16%) in group 1. Flap edema was significantly higher in group 2 (p < 0.001). At the end of the 1-year follow-up of the patients, we observed recurrence in only one (0.83%) eye in group 1 and 14 (11.96%) eyes in group 2. The recurrence rate of group 1 was significantly less than that of group 2 (p < 0.001).
Conclusions The simplified technique of tenon-free conjunctival autograft preparation and limited tenon removal yielded better clinical outcomes without serious complications. Additionally, this technique shortened the surgical time and reduced surgeon-dependent factors.
Quality Requirements for gynecological ultrasound examinations of DEGUM level II – Recommendations of the Sections/Working Groups Gynecology and Obstetrics of DEGUM, ÖGUM and SGUM
Authors: Hoopmann Markus , Tutschek Boris , Merz Eberhard , Eichhorn Karl-Heinz , Kagan Karl Oliver , Heling Kai-Sven , Faber Renaldo , Rempen Andreas , Kaehler Christiane , Manegold-Brauer Gwendolin , Helmy Samir , Klaritsch Philipp , Grab Dieter 
Published: November 2021

AbstractGynecological sonography is the central and most frequently used technical examination method used by gynecologists. Its focus is on the clarification of masses of the uterus and the adnexa, fertility diagnosis, clarification of bleeding disorders and chronic and acute pelvic problems, pelvic floor and incontinence diagnosis as well as the differential diagnosis of disturbed early pregnancy. The indication for diagnostic and therapeutic interventions, preoperative planning and postoperative controls are largely based on the findings of gynecological sonography. These examinations are particularly dependent on the experience of the examiner.Based on the proven multi-stage concept of obstetric diagnostics, gynecological sonography should primarily be performed by an experienced and specialized examiner in patients for whom the initial gynecological examinations have not yet led to a sufficient assessment of the findings. So that the expert status required for this has an objective basis, the Gynecology and Obstetrics Section of DEGUM in cooperation with ÖGUM and SGUM implemented the option of acquiring DEGUM Level II for gynecological sonography. The effectiveness of the care in the multi-level concept depends on the quality of the ultrasound examination at level I. Quality requirements for the basic examination and the differentiation between the basic and further examination have therefore already been defined by DEGUM/ÖGUM. The present work is intended to set out quality requirements for gynecological sonography of DEGUM level II and for the correspondingly certified gynecologists.Common pathologies from gynecological sonography and requirements for imaging and documentation are described.
Air pollution interacts with genetic risk to influence cortical networks implicated in depression
Authors: Li Zhi , Yan Hao , Zhang Xiao , Shah Shefali , Yang Guang , Chen Qiang , Han Shizhong , Zhang Dai , Weinberger Daniel R. , Yue Weihua , Tan Hao Yang 
Published: November 2021

Significance
Air pollution is ubiquitous and may increase neuropsychiatric risk, including for depression. However, the neural underpinnings and whether this environmental risk acts independently or interactively with genetic risk mechanisms are not well understood. In healthy individuals exposed to significant air pollution, we find that combined high air pollution exposures and relatively high polygenic risk for depression disproportionately augmented stress-related effects on brain circuitry. The coexpression of depression-associated genes across the brain tracked corresponding brain connectivity, driven by individuals with higher polygenic risk and with higher exposures to air pollution. These findings add to the mechanistic understanding of brain processes implicated in how individuals with high genetic risk for depression may be particularly vulnerable to the brain effects of air pollution.
Modular origins of high-amplitude cofluctuations in fine-scale functional connectivity dynamics
Authors: Pope Maria , Fukushima Makoto , Betzel Richard F. , Sporns Olaf 
Published: November 2021

Significance
Brain regions engage in complex patterns of activation over time. Relating these patterns to neural processing is a central challenge in cognitive neuroscience. Recent work has identified brief intermittent bursts of brain-wide signal cofluctuations, called events, and shown that events drive functional connectivity. The origins of events are unclear. Here, we address this gap in knowledge by implementing computational models of neural oscillators coupled by anatomical connections derived from maps of the human cerebral cortex. Analysis of the emerging large-scale brain dynamics reveals brief episodes with high system-wide signal amplitudes. Simulated events closely correspond to those seen recently in empirical recordings. Notably, simulated events are significantly aligned with underlying structural modules, thus suggesting an important role of modular network organization.