bluuebunny/crossref_metadata_2025_split huggingface dataset:
An updated global atmospheric paleo‐reanalysis covering the last 400 years
Authors: Valler Veronika , Franke Jörg , Brugnara Yuri , Brönnimann Stefan 
Published: May 2021

AbstractData assimilation techniques are becoming increasingly popular for climate reconstruction. They benefit from estimating past climate states from both observation information and from model simulations. The first monthly global paleo‐reanalysis (EKF400) was generated over the 1600 and 2005 time period, and it provides estimates of several atmospheric fields. Here we present a new, considerably improved version of EKF400 (EKF400v2). EKF400v2 uses atmospheric‐only general circulation model simulations with a greatly extended observational network of early instrumental temperature and pressure data, documentary evidences and tree‐ring width and density proxy records. Furthermore, new observation types such as monthly precipitation amounts, number of wet days and coral proxy records were also included in the assimilation. In the version 2 system, the assimilation process has undergone methodological improvements such as the background‐error covariance matrix is estimated with a blending technique of a time‐dependent and a climatological covariance matrices. In general, the applied modifications resulted in enhanced reconstruction skill compared to version 1, especially in precipitation, sea‐level pressure and other variables beside the mostly assimilated temperature data, which already had high quality in the previous version. Additionally, two case studies are presented to demonstrate the applicability of EKF400v2 to analyse past climate variations and extreme events, as well as to investigate large‐scale climate dynamics.
Oligodendrocytes are susceptible to Zika virus infection in a mouse model of perinatal exposure: Implications for CNS complications
Authors: Schultz Verena , Barrie Jennifer A. , Donald Claire L. , Crawford Colin L. , Mullin Margaret , Anderson Thomas J. , Solomon Tom , Barnett Susan C. , Linington Christopher , Kohl Alain , Willison Hugh J. , Edgar Julia M. 
Published: May 2021

AbstractSome children with proven intrauterine Zika virus (ZIKV) infection who were born asymptomatic subsequently manifested neurodevelopmental delays, pointing to impairment of development perinatally and postnatally. To model this, we infected postnatal day (P) 5–6 (equivalent to the perinatal period in humans) susceptible mice with a mammalian cell‐propagated ZIKV clinical isolate from the Brazilian outbreak in 2015. All infected mice appeared normal up to 4 days post‐intraperitoneal inoculation (dpi), but rapidly developed severe clinical signs at 5–6 dpi. All nervous tissue examined at 5/6 dpi appeared grossly normal. However, anti‐ZIKV positive cells were observed in the optic nerve, brain, and spinal cord; predominantly in white matter. Co‐labeling with cell type specific markers demonstrated oligodendrocytes and astrocytes support productive infection. Rarely, ZIKV positive neurons were observed. In spinal cord white matter, which we examined in detail, apoptotic cells were evident; the density of oligodendrocytes was significantly reduced; and there was localized microglial reactivity including expression of the NLRP3 inflammasome. Together, our observations demonstrate that a clinically relevant ZIKV isolate can directly impact oligodendrocytes. As primary oligodendrocyte cell death can lead later to secondary autoimmune demyelination, our observations may help explain neurodevelopmental delays in infants appearing asymptomatic at birth and commend lifetime surveillance.
Submandibular gland degloving: A minimally invasive function‐preserving surgical approach for benign diseases
Authors: Piras Antonio , Rizzo Davide , Gallus Roberto , Artuso Alberto , Bussu Francesco 
Published: May 2021

AbstractIn the Video S1, a modified technique for submandibular gland resection in benign disease is shown. The main plane of dissection is below the fascia and immediately superficial to the fibrous capsule of the gland. The video shows the surgical steps and the structures that become evident along the procedure and illustrates some tips and tricks. Facial vessels are dissected, easily spared, and not ligated as it occurs in the classical technique. This technical variant is minimally invasive, respectful of anatomy, and through preservation of the fascial layer investing the gland aims at reducing the risk of injury to the marginalis mandibulae branch of the facial nerve, which lies within the fascia itself.
Sleep as a window on the sensorimotor foundations of the developing hippocampus
Authors: Del Rio‐Bermudez Carlos , Blumberg Mark S. 
Published: May 2021

AbstractThe hippocampal formation plays established roles in learning, memory, and related cognitive functions. Recent findings also suggest that the hippocampus integrates sensory feedback from self‐generated movements to modulate ongoing motor responses in a changing environment. Such findings support the view of Bland and Oddie (Behavioural Brain Research, 2001, 127, 119–136) that the hippocampus is a site of sensorimotor integration. In further support of this view, we review neurophysiological evidence in developing rats that hippocampal function is built on a sensorimotor foundation and that this foundation is especially evident early in development. Moreover, at those ages when the hippocampus is first establishing functional connectivity with distant sensory and motor structures, that connectivity is preferentially expressed during periods of active (or REM) sleep. These findings reinforce the notion that sleep, as the predominant state of early infancy, provides a critical context for sensorimotor development, including development of the hippocampus and its associated network.
Risk factors of ocular morbidity among under‐five years old children in Khartoum State‐ Sudan‐ 2020
Authors: Ibrahim Mohanad Kamaleldin Mahmoud , Wolvaardt Jacqueline Elizabeth , Elnimeiri Mustafa Khidir Mustafa 
Published: May 2021

AbstractBackground and AimsVisual impairment in early childhood can significantly affect the development of visual, motor, and cognitive function and potentially lead to long‐term adverse psychosocial consequences. This study aimed to identify the risk factors of ocular morbidity among under 5‐year old children in Khartoum State, Sudan.MethodsA cross‐sectional study was conducted in three tertiary eye care hospitals in Khartoum State, Sudan. The study included 391 children under the age of 5 years. The parent(s) were interviewed using a precoded, pretested, closed‐ended questionnaire that included questions regarding socio‐demographic profile and possible risk factors. Data were analyzed using Statistical Package for the Social Sciences (version 21.0). A P‐value of less than .05 was regarded as significant.ResultsThere was a significant association between participants with diabetes mellitus and poor vision (P‐value <.001). Two‐thirds of participants (57%) with visual impairment had mothers, who reportedly attended antenatal care services regularly (P‐value .001), revealing a significant statistical association. Maternal diseases, specifically diabetes, was identified as a risk factor for poor visual acuity in their offspring (P‐value <.001). A significant relation was revealed between family history of eye disease and the degree of relationship to the affected participant (P‐value <.001). There was an association between watching TV and current visual acuity (P‐value <.001); as well as using mobile phones and current visual acuity (P‐value <.001). Multilinear analysis revealed the stronger influence of TV watching rather than the use of mobile phones (P‐value <.001).ConclusionsDiabetes, diabetic mothers, a family history of ocular morbidity, watching television, and using mobile phones emerged as significant risk factors of ocular morbidity among children under the age of 5 years in this study. Many of these risk factors are either modifiable or controllable ocular morbidities among under‐five children can be reduced with suitable interventions.
The PI3K pathway as a therapeutic intervention point in inflammatory bowel disease
Authors: Winkelmann Paula , Unterweger Anna‐Lena , Khullar Diya , Beigel Florian , Koletzko Leandra , Siebeck Matthias , Gropp Roswitha 
Published: May 2021

AbstractWith glucose being the preferred source of energy in activated T cells, targeting glycolysis has become an attractive therapeutic intervention point for chronic inflammatory bowel diseases (IBD). The switch to glycolysis is mediated by phosphoinositide‐3‐kinases (PI3K) which relay signals from surface receptors to the AKT pathway. We first confirmed by analysis of the oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) that metabolism is shifted towards glycolysis in IBD patients as compared to non‐IBD donors. In contrast to non‐IBD donors, OCR correlated with ECAR (IBD: cor = 0.79, p = 2E‐10; non‐IBD: cor = 0.37, p = n.s.), in IBD patients. Second, we tested the PI3K inhibitor copanlisib as a potential therapeutic. Ex vivo, copanlisib suppressed the ECAR significantly in T cells activated by anti‐CD3 antibodies and significantly decreased ECAR rates in the presence of copanlisib (anti‐CD3: 58.24 ± 29.06; copanlisib: 43.16 ± 20.23, p < .000. In addition, copanlisib impaired the activation of CD4+ CD25+ T cells (anti‐CD3: 42.15 ± 21.46; anti‐CD3 + copanlisib: 26.06 ± 21.82 p = .013) and the secretion of cytokines (IFNγ: anti‐CD3: 6332.0 ± 5707.61 pmol/ml; anti‐CD3 + copanlisib: 6332.0 ± 5707.61, p = .018). In vivo, copanlisib significantly improved the histological scores (ethanol: 8.5 ± 3.81; copanlisib: 4.57 ± 2.82, p = .006) in the NSG‐UC mouse model. Orthogonal partial least square analysis confirmed the efficacy of copanlisib. These data suggest that the PI3K pathway provides an attractive therapeutic intervention point in IBD for patients in relapse. Targeting metabolic pathways have the potential to develop phase dependent therapies.
CCL17‐expressing dendritic cells in the intestine are preferentially infected by Salmonella but CCL17 plays a redundant role in systemic dissemination
Authors: Erazo Anna B. , Wang Nancy , Standke Lena , Semeniuk Adrian D. , Fülle Lorenz , Cengiz Sevgi C. , Thiem Manja , Weighardt Heike , Strugnell Richard A. , Förster Irmgard 
Published: May 2021

AbstractIntroduction
Salmonella spp. are a recognized and global cause of serious health issues from gastroenteritis to invasive disease. The mouse model of human typhoid fever, which uses Salmonella enterica serovar Typhimurium (STM) in susceptible mouse strains, has revealed that the bacteria gain access to extraintestinal tissues from the gastrointestinal tract to cause severe systemic disease. Previous analysis of the immune responses against Salmonella spp. revealed the crucial role played by dendritic cells (DCs) in carrying STM from the intestinal mucosa to the mesenteric lymph nodes (mLNs), a key site for antigen presentation and T cell activation. In this study, we investigated the influence of chemokine CCL17 on the dissemination of STM.MethodsWT, CCL17/EGFP reporter, or CCL17‐deficient mice were infected orally with STM (SL1344) or mCherry‐expressing STM for 1–3 days. Colocalization of STM with CCL17‐expressing DCs in Peyer's patches (PP) and mLN was analyzed by fluorescence microscopy. In addition, DCs and myeloid cell populations from naïve and Salmonella‐infected mice were analyzed by flow cytometry. Bacterial load was determined in PP, mLN, spleen, and liver 1 and 3 days after infection.ResultsHistological analysis revealed that CCL17‐expressing cells are located in close proximity to STM in the dome area of PP. We show that, in mLN, STM were preferentially located within CCL17+ rather than CCL17− DCs, besides other mononuclear phagocytes, and identified the CD103+ CD11b− DC subset as the main STM‐carrying DC population in the intestine. STM infection triggered upregulation of CCL17 expression in specific intestinal DC subsets in a tissue‐specific manner. The dissemination of STM from the gut to the mLN, however, was only moderately influenced by the presence of CCL17.ConclusionCCL17‐expressing DCs were preferentially infected by Salmonella in the intestine in comparison to other DC. Nevertheless, the production of CCL17 was not essential for the early dissemination of Salmonella from the gut to systemic organs.
A Distinct Variant of Pseudohypoparathyroidism (PHP) First Characterized Some 41 Years Ago Is Caused by the 3‐kbSTX16 Deletion
Authors: Kiuchi Zentaro , Reyes Monica , Brickman Arnold S , Jüppner Harald 
Published: May 2021

ABSTRACTIn 1980, Farfel and colleagues (NEJM, 1980;303:237–42) provided first evidence for two distinct variants of pseudohypoparathyroidism (PHP) that present with hypocalcemia and impaired parathyroid hormone (PTH)‐stimulated urinary cAMP and phosphate excretion, either in the presence or absence of Albright's hereditary osteodystrophy (AHO). An “abnormal allele” and an “unexpressed allele” were considered as underlying defects, predictions that turned out to be correct for both forms of PHP. Patients affected by the first variant (now referred to as PHP1A) were later shown to be carriers of inactivating mutations involving the maternal GNAS exons encoding Gsα. Patients affected by the second variant (now referred to as PHP1B) were shown in the current study to carry a maternal 3‐kb STX16 deletion, the most frequent cause of autosomal dominant PHP1B, which is associated with loss of methylation at GNAS exon A/B that reduces or abolishes maternal Gsα expression. However, the distinct maternal mutations leading to either PHP1A or PHP1B are disease‐causing only because paternal Gsα expression in the proximal renal tubules is silenced, ie, “unexpressed.” Our findings resolve at the molecular level carefully conducted investigations reported some 41 years ago that had provided first clues for the existence of two distinct PHP variants. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Impact of Tenofovir Disoproxil‐Induced Fanconi Syndrome on Bone Material Quality: A Case Report
Authors: Hadzimuratovic Benjamin , Haschka Judith , Hartmann Markus A , Blouin Stéphane , Fratzl‐Zelman Nadja , Zwerina Jochen , Kocijan Roland 
Published: May 2021

ABSTRACTTenofovir is a nucleotide analog reverse‐transcriptase inhibitor (NtARTI) used for treatment of chronic hepatitis B and human immunodeficiency virus (HIV). Fanconi syndrome (FS) is a condition affecting the proximal tubules of the kidney, leading to increased passage and impaired reabsorption of various small molecules such as glucose, phosphate, bicarbonate, and amino acids. Tenofovir disoproxil fumarate (TDF) is one of two pro‐drugs of tenofovir associated with a greater nephrotoxicity and renal complications such as FS with subsequent osteomalacia, acute kidney injury, and reduction of glomerular filtration rate (GFR) compared with tenofovir alafenamide (TAF). We present the case of a 33‐year‐old white woman treated with TDF because of chronic hepatitis B infection suffering four atraumatic fractures over the period of 2 years. The patient was taken off the TDF regimen 3 months before presentation. Initial blood and urine samples suggested the presence of TDF‐induced osteomalacia, which was confirmed by transiliac bone biopsy and histomorphometry. Moreover, bone mineral density distribution (BMDD) by quantitative backscattered electron imaging (qBEI) analysis showed that approximately 56% of the bone surface was normally mineralized and 44% showed a reduced mineralization consistent with the presence of osteomalacia. The patient made a significant recovery upon cessation of the causative agent. This case report emphasizes the use of bone biopsy, histomorphometry and qBEI in confirming the diagnosis of drug‐induced Fanconi syndrome and associated osteomalacia. © 2021 The Authors.JBMR Pluspublished by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Design, synthesis, and in vitro/vivo anticancer activity of 4‐substituted 7‐(3‐fluoro‐4‐methoxybenzyl)‐7H‐pyrrolo[2,3‐d]pyrimidines
Authors: Tsai Pei‐Yi , Hu Gong‐Siang , Huang Po‐Hsun , Jheng Huei‐Lin , Lan Chi‐Hsuan , Chen You‐Sin , Chang Jia‐Ming , Chuang Shih‐Hsien , Huang Jiann‐Jyh 
Published: May 2021

AbstractIn this paper, we report the design and synthesis of 4‐substituted 7‐(3‐fluoro‐4‐methoxybenzyl)‐7H‐pyrrolo[2,3‐d]pyrimidines of scaffold 6 as anticancer agents. A total of 19 derivatives of scaffold 6 bearing a C‐4 alkoxy, dialkylamino, alkyl, vinyl, or phenyl substituent were synthesized and evaluated. Among them, compound 6q having a C‐4 ethyl group and a benzylic methyl group showed the most potent in vitro anticancer activity, inhibiting the proliferation of Hela, MDA‐MB‐231, and MDA‐MB‐426 cancer cells at submicromolar concentrations (GI50: 0.11–0.58 μM). Compound 6q arrested the cell cycle of MDA‐MB‐231 at G2/M phase, and showed in vivo activity on nude mice bearing MDA‐MB‐231 xenografts. Compound 6q has served as an anticancer lead for further optimization.
The extended binary quadratic residue code of length 42 holds a 3‐design
Authors: Bonnecaze A. , Solé P. 
Published: May 2021

AbstractThe codewords of weight 10 of the [42, 21, 10] extended binary quadratic residue code are shown to hold a design of parameters . Its automorphism group is isomorphic to . Its existence can be explained neither by a transitivity argument, nor by the Assmus–Mattson theorem.
Elevated levels of interleukin‐35 and interleukin‐37 in adult patients with obstructive sleep apnea
Authors: Chen Bi , Liu Ya‐nan , Ji Lei , Liu Ping‐li , He Jun , Gan Yu‐ying , Ji Gui‐juan , Zhu Shu‐yang , Zhang Wen‐hui 
Published: May 2021

AbstractBackgroundSystemic inflammation has a critical role in the pathogenesis of obstructive sleep apnea (OSA). Interleukin (IL)‐35 and IL‐37 have been identified as novel immune‐modulating cytokines with anti‐inflammatory activities in numerous types of inflammatory disease. The present study aimed to examine the serum levels of IL‐35 and IL‐37 in patients with OSA, and to investigate their associations with the severity of OSA.MethodsA total of 97 patients, including 67 cases of OSA and 30 age‐ and gender‐matched healthy control subjects, were enrolled in the present study. All subjects were evaluated by overnight polysomnography. Serum IL‐35, IL‐37, and pro‐inflammatory cytokine IL‐1β levels were examined by ELISA.ResultsCompared with those in the control subjects, serum IL‐35, IL‐37, and IL‐1β levels were significantly elevated in patients with mild, moderate, or severe OSA. Furthermore, a severity‐dependent increase in serum IL‐35 and IL‐37 levels was observed in patients with OSA. IL‐35 and IL‐37 levels were positively correlated with the apnea‐hypopnea index (r = 0.742 and 0.578, respectively; both p < 0.001), while they were negatively correlated with the mean oxygen saturation (r = −0.461 and −0.339, respectively; both p < 0.001) and lowest oxyhaemoglobin saturation (r = −0.616 and −0.463, respectively; both p < 0.001) in patients with OSA. In addition, a positive correlation was observed between IL‐35 or IL‐37 and IL‐1β levels (all p < 0.001).ConclusionThe serum levels of IL‐35 and IL‐37 were significantly increased in patients with OSA and associated with the severity of OSA, implying that IL‐35 and IL‐37 may have a protective role in OSA by counteracting inflammatory responses.
Diagnostic value of serum human Galactomannan aspergillus antigen and 1,3‐beta‐D‐glucan in immunocompromised patient suspected fungal infection
Authors: Susianti Hani , Parmadi Lydiana , Firani Novi Khila , Setyawan Ungky Agus , Sartono Teguh Rahayu 
Published: May 2021

AbstractBackgroundThe prevalence of fungal infection (FI) in developing countries is high, but the diagnosis of FI is still challenging to determine, so it is needed evaluation of biomarkers other than microbiological culture, because the culture has low sensitivity, high cost, not available in every laboratory and needs a long time. The detection of human galactomannan Aspergillus antigen (GAL) and 1,3‐beta‐D‐glucan (BDG) on the fungal cell wall could be the promising biomarkers for fungal infection. Neutropenia, lymphopenia and CD4T cells in the immunocompromised patients are essential factors, but these cell associations with BDG and GAL levels have not been evaluated yet. The study aimed to evaluate GAL and BDG for detecting fungal infection and their association with total leucocyte count, neutrophil, monocyte, lymphocyte and CD4T cells.MethodA cross‐sectional study was conducted among 86 patient with suspected FI. Fungal infection established using EORTC/MSG criteria. Serology test performed using ELISA. Leucocyte cells were measured using a haematology autoanalyser, and CD4T cells were analysed using BD FACSPresto. Statistical analysis obtained using Spearman's correlation coefficient, ROC curve analysis and 2 × 2 contingency table.ResultsSerum Galactomannan and BDG had a significant correlation with CD4T cells and total lymphocyte count (p < 0.05). The cut‐off OD GAL >0.3 had sensitivity 54.6%, specificity 87.5% and AUC 0.71; meanwhile, the BDG cut‐off >115.78 pg/ mL had sensitivity 71.2%, specificity 52.4% and AUC 0.63 for detecting fungal infection.ConclusionsThe immunocompromised patients can undergo GAL for determining the diagnose of FI. The lower the CD4T cells and total lymphocyte count, the higher the GAL and BDG serum levels.
Impact of loosening and straw addition to the subsoil on crop performance and nitrogen leaching: A lysimeter study
Authors: Getahun Gizachew Tarekegn , Bergström Lars , Rychel Vide , Kätterer Thomas , Kirchmann Holger 
Published: May 2021

AbstractPoor subsoil properties are difficult to ameliorate and detrimental to soil fertility and crop yield. The effects of loosening (L) and loosening + straw (LS) ∼60 Mg ha–1 into the subsoil (25–40 cm depth) on crop yield, water flow, and the nitrogen (N) balance components under bare soil conditions and a barley (Hordeum vulgare L.) crop were investigated in an about 21‐mo lysimeter study and compared with a control treatment. Undisturbed soil columns (n = 12) were excavated from an agricultural field in May 2016, installed at a lysimeter station, and exposed to outdoor climatic conditions in Uppsala, Sweden, in August 2016. Spring barley (‘Makof’) was grown between June and September 2017. Total N leaching loads over the 21 mo were high (74–193 kg ha–1). The LS treatment reduced the N load by 49% (P = .01) and 62% (P = .001) compared with the L and control treatments, respectively. Loosening reduced N load by 25% (P < .07) compared with the control. Emissions of N2O were low (0.04–0.07 kg N ha–1), and no differences were observed between treatments. Leaf relative chlorophyll content was lower in the LS treatment than in the L and control treatments (P < .05). Yield was also lowest in the LS treatment (5.8 Mg ha–1) and was 7 and 8.5% lower than in the control and L treatments (P > .05), respectively. These results suggest that LS can reduce N leaching. The overall effects of LS on crop performance and N removal and leaching should be further scrutinized in long‐term field studies.