bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Systemic Renin-Angiotensin System in COVID-19
Authors: Reindl-Schwaighofer Roman , Hödlmoser Sebastian , Domenig Oliver , Krenn Katharina , Eskandary Farsad , Schörgenhofer Christian , Rumpf Benedikt , Karolyi Mario , Traugott Marianna , Abrahamowicz Agnes , Tinhof Viktoria , Mayfurth Hannah , Rathkolb Vincent , Mußnig Sebastian , Schmölz Lukas , Ullrich Roman , Heinzel Andreas , König Franz , Binder Christina , Bonderman Diana , Strassl Robert ,   Elisabeth Puchhammer-St&#x00F6, Gorkiewicz Gregor , Aberle Judith , Jilma Bernd , Wenisch Christoph , Poglitsch Marko , Oberbauer Rainer , Zoufaly Alexander , Hecking Manfred 
Published: February 2022

Abstract

Introduction: SARS-CoV-2 gains cell entry via angiotensin-converting enzyme (ACE) 2, a membrane-bound enzyme of the “alternative” (alt) renin-angiotensin system (RAS). ACE2 counteracts angiotensin II by converting it to potentially protective angiotensin 1-7.Methods: Using mass spectrometry, we assessed key metabolites of the classical RAS (angiotensins I–II) and alt-RAS (angiotensins 1-7 and 1-5) pathways as well as ACE and ACE2 concentrations in 159 patients hospitalized with COVID-19, stratified by disease severity (severe, n=76; non-severe, n=83). Plasma renin activity (PRA-S) was calculated as the sum of RAS metabolites. We estimated ACE activity using the angiotensin II:I ratio (ACE-S) and estimated systemic alt-RAS activation using the ratio of alt-RAS axis metabolites to PRA-S (ALT-S). We applied mixed linear models to assess how PRA-S and ACE/ACE2 concentrations affected ALT-S, ACE-S, and angiotensins II and 1-7.Results: Median angiotensin I and II levels were higher with severe versus non-severe COVID-19 (both p<0.05), demonstrating activation of classical RAS. The difference disappeared with analysis limited to patients not taking a RAS inhibitor. ALT-S in severe COVID-19 increased with time (days 1–6: 0.12; days 11–16: 0.22) and correlated with ACE2 concentration (r=0.831). ACE-S was lower in severe versus non-severe COVID-19 (p<0.001), but ACE concentrations were similar between groups and weakly correlated with ACE-S (r=0.232). In mixed linear models, renin activity most strongly predicted angiotensin II and 1-7 levels. ACE2 also predicted angiotensin 1-7 levels and ALT-S. No single factor or the combined model, however, could fully explain ACE-S.Conclusions: Angiotensin II was elevated in severe COVID-19 but markedly influenced by RAS inhibitors and driven by overall RAS activation. ACE-S was significantly lower with severe COVID-19 and did not correlate with ACE concentrations. A shift to the alt-RAS axis because of increased ACE2 could partially explain the relative reduction in angiotensin II levels.
Changes in belowground interactions between white lupin and wheat along nitrogen and phosphorus gradients
Authors: Boudsocq Simon , Cros Camille , Hinsinger Philippe , Lambers Hans 
Published: February 2022

Abstract
Background and aims The positive effects of cereal-legume intercropping can occur through complementarity and facilitation for the acquisition of soil nitrogen (N) and phosphorus (P). However, the magnitude of the benefits depends on the availability of such resources. To improve our understanding and design best-performing systems, we evaluated the performance and underlying mechanisms of a cereal-legume mixture on two crossed gradients of N and P. Methods In a pot experiment, wheat (Triticum aestivum L.) and white lupin (Lupinus albus L.) were grown separately or together on four levels of N combined with four levels of P. We compared biomass, N content, P content, shoot-to-root biomass ratios and white lupin production of cluster roots and nodules of sole crops with those of intercrops. We used the relative interaction intensity index to determine how the nature of the interaction between the two species changed along the two resource gradients. Results Regardless of N and P supply, combined biomass and N content of intercropped wheat and white lupin were 29% and 23% greater, respectively. Intercropping increased P content by 34%, on average, particularly at the lowest P supply. While wheat benefited from intercropping in all treatments, white lupin’s performances decreased with increasing N and P supply, resulting in a shift from mutualism to competition along the two gradients and compensation mechanisms between the two species. Conclusion Nutrient availability negatively influenced the nature and mechanisms of wheat-lupin interaction. However, mutualistic interactions were the less productive, while competition was associated with the more productive situations.
Identifying Key Genes and Functionally Enriched Pathways in B cells from Peripheral Blood of Rheumatoid Arthritis Patients by Bioinformatics Analysis and Validation
Authors: Wu Fengping , Gao Jinfang , Zhao Xingxing , Kang Jie , Wang Xuexue , Niu Qing , Liu Jiaxi , Zhang Liyun 
Published: February 2022

Abstract
Rheumatoid arthritis is a common chronic inflammatory disease. B cells are critical for the development of RA, but so far, we still know little about the role of B cells in the pathogenesis of RA. In the present study, we downloaded mRNA expression profiles of B cells from the peripheral blood (BCPB) of 7 RA patients and 9 healthy people from the Gene Expression Omnibus (GEO) database. Using weighted gene co-expression network analysis (WGCNA) in conjunction with differentially expressed gene (DEGs) analysis, we identified 23 RA-trait different expression genes. In the subsequent protein protein interaction (PPI) network constructed by RA-trait DEGs, we eventually identified 5 hub genes (TLR8, CCR2, CX3CR1, GIMAP6 and C1QA). Compared with healthy people, these hub genes are significantly highly expressed in BCPB of RA patients in the dataset GSE4588. qRT-PCR results showed TLR8, CCR2, CX3CR1 were compatible with our bioinformatics analyses. Combined with other biological interpretations, our current study might provide a basis for identifying key genes and potential pathways related to the pathogenesis of BCPB of RA patients.
Conditioned media of mouse macrophages promote neuronal differentiation of mouse hippocampal cells
Authors: Öztürk Ayla Batu , Öztürk Nail Can , Ayaz Furkan 
Published: February 2022

Abstract
Understanding how the immune system associates with the pathophysiological hippocampal neurobiology in the neurodegenerative diseases is an emerging topic. Since the cellular population of hippocampal neurogenic niche is extraordinarily diverse, there is still a large gap in our understanding of the interactions between the immune cells and hippocampal neurons under even normal conditions, setting aside the disease conditions. To examine how the hippocampal neurons receive and respond to the cellular factors from the immune cells, we introduced the conditioned cell culture media (CM) of unstimulated, and lipopolysaccharide stimulated RAW 264.7 macrophages to HT22 hippocampal cells during and after they were exposed to neuronal differentiation environment to mimic the states during and after the initiation of the neurogenesis. Then, HT22 cell responses were further examined by assessing immunocytochemical expression of CR protein and mRNA levels of Ascl1, Bdnf, Nrf2 and Rac1 genes via semi quantitative image analysis and q-RT-PCR, respectively. Our results suggest that culturing the HT22 cells with the unstimulated CM of macrophages substantially increased calretinin protein expression, while the latter media containing quite high levels of inflammatory cytokines, measured by ELISA, resulted in decreased protein levels for Calretinin. Additionally, Ascl1 gene expression levels in HT22 cells had similar trends as calretinin protein levels in the presence of CM of stimulated versus unstimulated media. Whereas there was no substantial difference in the gene expression levels for the Bdnf, Nrf2 and Rac1 genes. Overall, our results imply that utilization of HT22 cells and macrophage interplay can be instructive to decipher the molecular mechanisms of cellular communication between the immune system cells and neurons. Our overarching aim is developing immunotherapy strategies by using non-CNS derived immune system cells to modulate the neurogenesis in disease conditions such as Multiple Sclerosis, Alzheimer’s and ALS to enable the recovery in the patients.
Osteoarticular Infections At A Pediatric Emergency Core Hospital In Japan
Authors: Takei Mikiko , Suga Kenichi , Takeuchi Shunsuke , Tayama Takahiro , Fujioka Keisuke , Ono Akemi , Shono Miki , Shichijo Koichi , Kosaka Hirofumi , Kobayashi Naoto , Kondo Shuji 
Published: February 2022

Abstract

Objectives: Osteomyelitis (OM) and septic arthritis (SA) in childhood might cause complications, sequelae, or even death if diagnosis and treatment are delayed. Early diagnosis of pediatric OM/SA depends on a healthcare system that is easily accessible and provides multidisciplinary management and early imaging studies. Here, we examined the outcomes of OM/SA at a pediatric emergency core hospital in Japan.Methods: This was a single-center, retrospective, observational cohort study　conducted at Tokushima Prefectural Central Hospital, a pediatric emergency core hospital in Japan. Pediatric outpatients who underwent magnetic resonance imaging at the hospital in the period 2012–2020 were recruited. Primary outcomes were sequelae, recurrent symptoms, chronicity, and death. The data collected included time from onset to first hospital visit, hospitalization, and initiation of effective antibiotics.Results: Fifteen OM/SA patients (9 OM, 4 SA, 2 OM+SA) were recruited. In these patients, symptoms were fever (100 %, n = 15), pain (93.3 %, n = 14), limited range of motion (73.3 %, n = 11), swelling (40.0 %, n = 6), and reluctance to feed (46.7 %, n = 7). The identified major pathogens included methicillin-susceptible Staphylococcus aureus (40.0 %, n = 6) and methicillin-resistant S. aureus (13.3 %, n = 2). Mean time from onset to first hospital visit, hospitalization, and initiation of effective antibiotics was 2 days, 3.9 ± 1.8 days, and 4.9 ± 2.2 days, respectively. All OM/SA patients recovered without complications or sequelae.Conclusions: In this study, all patients with OM/SA showed a good prognosis. Despite the small sample size, this pilot study suggests that the pediatric emergency core system in Japan provides early treatment and a good prognosis for patients diagnosed with OM/SA.
Effect of Tobacco Cultivation on Soil Fertility and Farmer’s Profitability in the Socio-Economic Perspective of Bangladesh
Authors: Joardar Jagadish Chandra , Fathema Kaniz , Basu Sudipa 
Published: February 2022

Abstract
Tobacco cultivation and production in Bangladesh have expanded by 99.68% and 219.4%, respectively, over the last decade. The study aimed to assess the impact of tobacco cultivation on soil fertility and to compare the soil fertility status of tobacco-based (TB) and non-tobacco-based (NTB) cropping fields. The study also compared the tobacco production cost and the financial cost-effectiveness of ranchers' land utilized for tobacco farming. The researchers used soil nutrient index (SNI) to analyze the soil fertility level of TB and NTB cropping fields. A total of 40 soil samples (20 TB and 20 NTB) were collected randomly from farmers' fields in Mirpur Upazila of Bangladesh's Kushtia district. Socio-demographic and financial data from 50 tobacco ranchers were collected from the investigation territory via a well-structured questionnaire. Soil nitrogen, phosphorus, sulfur, calcium and magnesium levels in TB fields were significantly lower than in NTB fields. Soil organic matter and pH in TB fields are substantially higher than in NTB fields. There was no substantial change in electrical conductivity or potassium. Based on the SNI results, the soil fertility in both cases was rated as medium. The average total cost of production for tobacco cultivation was 122190 BDT per acre of land. The average yield, all-in income, and net income per acre of land were 1292kg, 172851 BDT, and 50661 BDT, respectively, with a benefit-cost proportion of 1.42. Tobacco growers may benefit from reviewing the study's findings in making informed decisions on fertilizer applications for crops other than tobacco.
An F type star in a 51-minute orbital period eclipsing binary
Authors: Burdge Kevin , El-Badry Kareem , Marsh Thomas , Rappaport Saul , Brown Warren , Caiazzo Ilaria , Chakrabarty Deepto , Dhillon Vikram , Fuller Jim , Gänsicke Boris , Graham Matthew , Kara Erin , Kulkarni Shrii , Littlefair Stuart , Mroz Przemyslaw , Rodríguez-Gil Pablo , Roestel Jan van , Simcoe Robert , Bellm Eric , Drake Andrew , Dekany Richard , Masci Frank , Riddle Reed , Smith Roger , Prince Thomas 
Published: February 2022

Abstract
In over a thousand known cataclysmic variables (CVs), where a white dwarf is accreting from a hydrogen-rich star, only a dozen have orbital periods below 75 minutes1–8. One way to achieve these short periods requires the donor star to have undergone substantial nuclear evolution prior to interacting with the white dwarf9, 10, and it is expected that these objects will transition to helium accretion. These transitional CVs have been proposed as progenitors of helium CVs9–12 30 , also called AM CVn stars, one of the most abundant sources of gravitational radiation detectable by the Laser Space Interferometer Antenna13 . However, no known transitional CV is expected to reach an orbital period short enough to account for most of the helium CV population, leaving the role of this evolutionary pathway unclear. Here, we report observations of ZTF J1813+4251, a 51-minute orbital period fully eclipsing binary system consisting of an F type star, with a temperature comparable to that of the Sun but a density 100 times greater, accreting onto a white dwarf. Phase-resolved spectra, multi-band light curves and the broadband spectral energy distribution allow us to obtain precise and robust constraints on the masses, radii and temperatures of both components. Evolutionary modeling shows that ZTF J1813+4251 is destined to become a helium CV binary, reaching an orbital period under 20 minutes, rendering ZTF J1813+4251 a previously missing link between helium CV binaries and hydrogen-rich CVs.
A Novel Ensemble Method for Predicting Wheat Yield Using Feature Selection-based Deep Learning and Hyperspectral Vegetation Indices
Authors: Fei Shuaipeng , Li Lei , Han Zhiguo , Chen Zhen , Xiao Yonggui 
Published: February 2022

Abstract
Background: Wheat is an important food crop globally, and timely prediction of wheat yield in breeding efforts can improve the efficiency of selection. Traditional plant breeding based on grain yield selection is time-consuming, costly, and destructive. There is a great need for innovative methods to enhance efficiency and accelerate genetic gains in the breeding cycle. Results: In this study, a new ensemble learning method was developed to predict wheat yield by combining hyperspectral data and deep learning-based regression technology. For this, 207 wheat cultivars and breeding lines were grown under full and limited irrigation treatments, and their canopy hyperspectral reflectance was measured at the flowering, early grain fill (EGF), mid grain fill (MGF), and late grain fill (LGF). Firstly 115 vegetation indices (VIs) were extracted from the hyperspectral reflectance and combined with four feature selection methods i.e., mean decrease impurity (MDI), Boruta, FeaLect, and Relief to train deep neural network (DNN) models for yield prediction. Then, a novel ensemble learning framework was developed by combining the predicted values of selected and the full features using multiple linear regression (MLR). The results show that feature selection methods achieved higher yield prediction accuracy than the full features, where MDI method performed best across growth stages, with the mean R2 ranging from 0.634-0.666 (mean RMSE = 0.926-0.967 t ha-1). The proposed ensemble method outperformed all the FS methods across growth stages, with the mean R2 ranging from 0.648-0.679 (mean RMSE = 0.911-0.950 t ha-1). Conclusions: By integrating multiple FS methods and DNN, more prediction potential of hyperspectral data can be exploited, and this ensemble method is also applicable to trait estimation of other crops.
MGMT Gene Promoter Methylation by Pyrosequencing Method Correlates Volumetric Response and Neurological Status in IDH Wild-type Glioblastomas
Authors: Hosoya Tomohiro , Narita Yoshitaka , Takahashi Masamichi , Honda-Kitahara Mai , Miyakita Yasuji , Ohno Makoto , Yanagisawa Shunsuke , Omura Takaki , Kawauchi Daisuke , Tamura Yukie , Kikuchi Miyu , Nakano Tomoyuki , Yoshida Akihiko , Igaki Hiroshi , Matsushita Yuko , Ichimura Koichi 
Published: February 2022

Abstract
Purpose
Although the usefulness of O⁶-methylguanine DNA methyltransferase (MGMT) promoter methylation analysis for predicting response to chemoradiotherapy and the prognosis of patients with glioblastoma has been widely reported, there is still no consensus regarding how to define MGMT promoter methylation percentage (MGMTpm%) cutoffs by pyrosequencing method. The aim of this study was to determine the optimal cutoff value of MGMT promoter methylation status using volumetric analysis focused on the tumor volume ratio (TVR) measured by MRI.
Methods
This retrospective study included newly diagnosed IDH wild-type glioblastoma patients with residual tumor after surgery, followed by local radiotherapy with temozolomide. TVR was defined as the tumor volume at 6 months after the initial chemoradiotherapy administration divided by the tumor volume before the start of therapy. The mean MGMTpm% of 16 CpG islands (74–89) was analyzed using pyrosequencing. We statistically analyzed the correlation between MGMTpm%, TVR, and change in Karnofsky performance status (KPS).
Results
The study included 44 patients with residual tumors. Thirteen (92.9%) of 14 patients with MGMTpm% ≥23.9% showed 50% or more volumetric response, leading to prolonged survival, and 17 (70.8%) of 24 patients with MGMTpm% < 8.2% had progressive disease after initial chemoradiotherapy administration. Three (50.0%) of six patients with MGMTpm% 8.2% - < 23.9% had stable disease or partial response.
Conclusion
Evaluation of MGMTpm% by pyrosequencing is important in predicting the volumetric response and prognosis of glioblastoma patients with residual tumors.
The effect of Nizimuddinia zanardinii algae on biochemical parameters and histopathological changes induced by cholestatic liver fibrosis in male rats
Authors: Nasiri Modara , Hajikhani Ramin , Mortazavi Pejman , Ebrahim Mahsa Ale , Bananaj Maryam 
Published: February 2022

Abstract
Background: Liver fibrosis is an important health problem in the world; the excessive deposition of type 1 collagen is the most characteristic feature of liver fibrosis. Algae is one of the natural resources that contains biologically active compounds that have anti-inflammatory, antioxidant and immune-stimulating properties. In this study, the effect of brown algae Nizimuddinia zanardinii on liver damage caused by cholestatic liver fibrosis in rats was evaluated. Material and Methods: 54 male rats were randomly classified in nine groups: control, sham, BDL, treatment and Nizimuddinia control. In the treatment group, after BDL, rats were given Nizimuddinia zanradinii extract via intragastric gavage for 45 days (once per day). parameters contains ALT, AST, ALP, cholesterol, triglyceride, albumin, total protein, SOD and CAT and histopathological assessments evaluated. Results: Treatment with Nizimuddinia zanardinii significantly weakened these alterations. In order to, in the treatment groups, TGF-β1 expression was severe, noticeable and low, respectively. In treatment groups, α-SMA expression was remarkable and mildly observed in hepatocytes and hyperplastic bile ducts, respectively. Conclusions: Based on this study, the N. zanardinii extract may protect the liver and have anti-fibrotic effects through its antioxidant and reducing the expression of TGF-β1 and α-SMA.
Factors Associated With Non-Compliance to Diabetes Medication in a Rapidly Urbanizing Region in Ghana: A Mixed-Methods Study.
Authors: Berkoh Dorice A. , Owiredu William B. K. A. , Gyasi Samuel F. , Donkoh Emmanuel T. , Ngala Robert 
Published: February 2022

Abstract
Background
Failure to achieve adequate glycaemic control can lead to debilitating complications for diabetics. Strict compliance to prescribed diet, lifestyle and medication can prevent complications.
Methods
In order to examine factors accompanying non-compliance behaviour to diabetes medication in a rapidly urbanizing region of Ghana, a mixed approach was adopted. Study subjects (N: 160, mean age: 58.3) were interviewed at the Diabetic Clinic of the Brong-Ahafo Regional Hospital, Sunyani. Compliance to diabetes treatment was evaluated with an adapted Morisky Medication Adherence Scale (MMAS). Face-to-face interviews of 20 subjects allowed for more personalized exploration of psychosocial aspects of non-compliance. The interviews were audio recorded, transcribed verbatim, and coded using the Nvivo software. Qualitative data was processed and subjected to inductive thematic analysis.
Results
Majority of study participants reported an optimum (n = 121, 75.6%) level of compliance to diabetes medication, although some also reported poor compliance (n = 39, 24.4%). Qualitative responses received during interviews suggest that poor compliance may be attributable to misconceptions about religious beliefs and practices. Psychosocial factors relating to felt stress, the inevitability of fate and compliance fatigue were also discovered to undermine compliance. Non-compliance behaviour was also explained by socioeconomic status and barriers to health-seeking behaviour.
Conclusion
Reported medication compliance was among the highest in out-patient settings in Ghana. However, contextual determinants of non-compliance have to be addressed. Efforts to improve compliance to diabetic medication could benefit from interventions that address superstition, target psychological aspects of chronic disease management and remove operational barriers to healthcare delivery such as transportation costs and long waiting times.
Large-gap Peripheral Nerve Repair Using Xenogeneic Transplants in Rhesus Macaques
Authors: Holzer Paul , Chang Elizabeth J. , Tarlton Jamie , Lu Diana , Gillespie Natasha , Rogers Kaitlyn , Adkins Jon , Metea Monica , LaRochelle Alan , Wicks Joan , Onel Buket , Gullans Steve , Doloff Joshua C. , Scobie Linda , Cetrulo Curtis L. , Monroy Rod 
Published: February 2022

Abstract
Surgical intervention is required to successfully treat severe, large-gap (≥4 cm) peripheral nerve injuries. However, all existing treatments have shortcomings and an alternative to the use of autologous nerves is needed. Human andporcine nerves are physiologically similar, with comparable dimensions and architecture, presence and distribution of Schwann cells, and conserved features of the extracellular matrix (ECM). We report the repair of fully transected radial nerves in 10 Rhesus Macaques using viable, whole sciatic nerve from genetically engineered (GalT-KO), designated pathogen free (DPF) porcine donors. This resulted in the regeneration of the transected nerve, recovery of wrist extension function, distal muscle reinnervation, and recovery of nerve conduction velocities and compound muscle action potentials statistically equivalent to autologous controls. We also demonstrate the absence of immune rejection, systemic porcine cell migration, and detectable residual porcine material. Our findings support the safety and efficacy of viable porcine nerve transplants, suggest the interchangeable therapeutic use of cross-species cells, and highlight the broader clinical potential of xenotransplantation.