bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trends and Variability of North American Cool-Season Extratropical Cyclones: 1979–2019
Authors: Fritzen Robert , Lang Victoria , Gensini Vittorio A. 
Published: August 2021

AbstractExtratropical cyclones are the primary driver of sensible weather conditions across the mid-latitudes of North America, often generating various types of precipitation, gusty non-convective winds, and severe convective storms throughout portions of the annual cycle. Given ongoing modifications of the zonal atmospheric thermal gradient due to anthropogenic forcing, analyzing the historical characteristics of these systems presents an important research question. Using the North American Regional Reanalysis, boreal cool-season (October–April) extratropical cyclones for the period 1979–2019 were identified, tracked, and classified based on their genesis location. Additionally, bomb cyclones—extratropical cyclones that recorded a latitude normalized pressure fall of 24 hPa in 24-hr—were identified and stratified for additional analysis. Cyclone lifespan across the domain exhibits a log-linear relationship, with 99% of all cyclones tracked lasting less than 8 days. On average, ≈ 270 cyclones were tracked across the analysis domain per year, with an average of ≈ 18 year−1 being classified as bomb cyclones. The average number of cyclones in the analysis domain has decreased in the last 20 years from 290 year−1 during the period 1979–1999 to 250 year−1 during the period 2000–2019. Spatially, decreasing trends in the frequency of cyclone track counts were noted across a majority of the analysis domain, with the most significant decreases found in Canada’s Northwest Territories, Colorado, and east of the Graah mountain range. No significant interannual or spatial trends were noted with bomb cyclone frequency.
Patient, parent and educator perspectives on paediatric concussion
Authors: Grool Anne M , DeMatteo Carol , Reed Nick , Newhook Dennis , Zemek Roger 
Published: August 2021

Background Past research on paediatric concussion awareness, management, impact and outcome priorities has focused on health care professionals and sports organizations, yet little is known about patient, parent and educator perspectives. Methods To address this knowledge gap, we conducted a qualitative descriptive study using semi-structured interviews with three participant groups: patient-participants including children with acute or chronic concussion; parent-participants including caregivers of children at risk for or with history of concussion; and educator-participants including teachers and athletic coaches from three Ontario secondary schools. We designed our interview guide to elicit participants’ perspectives across four domains: concussion awareness, concussion experience, support and resources, and outcome priorities. We analyzed our resultant data using a qualitative content analysis approach. Results Nine paediatric patient-participants, 17 parent-participants, and 14 educator-participants completed the study. Participants described concussion as a serious health concern and attributed greater concussion awareness to increased media attention and concussion protocol implementation within schools/sports. While most educator-participants regarded concussion protocols positively, some feared student manipulation. Parent- and educator-participants desired consistent information and resources from reliable sources. The impact of concussion ranged from a few days to prolonged absences (from school, sports, and socializing) and necessitated accommodations in both academic and sport settings. Short-term problems (e.g., decreased peer-contact) primarily troubled patient-participants, whereas long-term problems (e.g., impaired academics, psychological stress) concerned parent and educator groups. Conclusion Patients, parents and educators worry about the consequences of paediatric concussion. Initial concussion recovery in youth should focus on a timely return to academics and on minimizing social isolation by ensuring peer-contact during recovery.
Insertion of atypical glycans into the tumor antigen-binding site identifies DLBCLs with distinct origin and behavior
Authors: Chiodin Giorgia , Allen Joel D. , Bryant Dean J. , Rock Philip , Martino Enrica A. , Valle-Argos Beatriz , Duriez Patrick J. , Watanabe Yasunori , Henderson Isla , Blachly James S. , McCann Katy J. , Strefford Jonathan C. , Packham Graham , Geijtenbeek Teunis B. H. , Figdor Carl G. , Wright George W. , Staudt Louis M. , Burack Richard , Bowden Thomas A. , Crispin Max , Stevenson Freda K. , Forconi Francesco 
Published: August 2021

AbstractGlycosylation of the surface immunoglobulin (Ig) variable region is a remarkable follicular lymphoma–associated feature rarely seen in normal B cells. Here, we define a subset of diffuse large B-cell lymphomas (DLBCLs) that acquire N-glycosylation sites selectively in the Ig complementarity-determining regions (CDRs) of the antigen-binding sites. Mass spectrometry and X-ray crystallography demonstrate how the inserted glycans are stalled at oligomannose-type structures because they are buried in the CDR loops. Acquisition of sites occurs in ∼50% of germinal-center B-cell–like DLBCL (GCB-DLBCL), mainly of the genetic EZB subtype, irrespective of IGHV-D-J use. This markedly contrasts with the activated B-cell–like DLBCL Ig, which rarely has sites in the CDR and does not seem to acquire oligomannose-type structures. Acquisition of CDR-located acceptor sites associates with mutations of epigenetic regulators and BCL2 translocations, indicating an origin shared with follicular lymphoma. Within the EZB subtype, these sites are associated with more rapid disease progression and with significant gene set enrichment of the B-cell receptor, PI3K/AKT/MTORC1 pathway, glucose metabolism, and MYC signaling pathways, particularly in the fraction devoid of MYC translocations. The oligomannose-type glycans on the lymphoma cells interact with the candidate lectin dendritic cell–specific intercellular adhesion molecule 3 grabbing non-integrin (DC-SIGN), mediating low-level signals, and lectin-expressing cells form clusters with lymphoma cells. Both clustering and signaling are inhibited by antibodies specifically targeting the DC-SIGN carbohydrate recognition domain. Oligomannosylation of the tumor Ig is a posttranslational modification that readily identifies a distinct GCB-DLBCL category with more aggressive clinical behavior, and it could be a potential precise therapeutic target via antibody-mediated inhibition of the tumor Ig interaction with DC-SIGN–expressing M2-polarized macrophages.
T-follicular helper cell expansion and chronic T-cell activation are characteristic immune anomalies in Evans syndrome
Authors: Kumar Deepak , Prince Chengyu , Bennett Carolyn M. , Briones Michael , Lucas Laura , Russell Athena , Patel Kiran , Chonat Satheesh , Graciaa Sara , Edington Holly , White Michael H. , Kobrynski Lisa , Abdalgani Manar , Parikh Suhag , Chandra Sharat , Bleesing Jack , Marsh Rebecca , Park Sunita , Waller Edmund K. , Prahalad Sampath , Chandrakasan Shanmuganathan 
Published: August 2021

Abstract
Pediatric Evans syndrome (pES) is increasingly identified as the presenting manifestation of several inborn errors of immunity. Despite an improved understanding of genetic defects in pES, the underlying immunobiology of pES is poorly defined, and characteristic diagnostic immune parameters are lacking. We describe the immune characteristics of 24 patients with pES and compared them with 22 patients with chronic immune thrombocytopenia (cITP) and 24 healthy controls (HCs). Compared with patients with cITP and HC, patients with pES had increased circulating T-follicular helper cells (cTfh), increased T-cell activation, and decreased naïve CD4+ T cells for age. Despite normal or high immunoglobulin G (IgG) in most pES at presentation, class-switched memory B cells were decreased. Within the cTfh subset, we noted features of postactivation exhaustion with upregulation of several canonical checkpoint inhibitors. T-cell receptor β chain (TCR-β) repertoire analysis of cTfh cells revealed increased oligoclonality in patients with pES compared with HCs. Among patients with pES, those without a known gene defect had a similar characteristic immune abnormality as patients with defined genetic defects. Similarly, patients with pES with normal IgG had similar T-cell abnormalities as patients with low IgG. Because genetic defects have been identified in less than half of patients with pES, our findings of similar immune abnormalities across all patients with pES help establish a common characteristic immunopathology in pES, irrespective of the underlying genetic etiology.
A young woman presented with massive pulmonary embolism with inferior vena cava thrombus as a complication of nephrotic syndrome: a case report
Authors: Jeele Mohamed Osman Omar , Addow Rukia Omar Barei , Mohamud Mohamed Farah Yusuf 
Published: August 2021

AbstractNephrotic syndrome (NS) was first described in 1827 as the presence of proteinuria of ≥ 3.5 g/24 h, hypoalbuminemia < 3.0 g/dl, peripheral edema, hyperlipidemia, lipiduria, and increased thrombotic risk. Nephrotic syndrome has an incidence of three cases per 100,000 each year in adults. Nephrotic syndrome also has serious complications due to hypercoagulable state in both various venous and arteries which could lead thromboembolic events. The pathophysiology of hypercoagulability in the nephrotic syndrome is due to an imbalance of prothrombotic and antithrombotic factors, as well as impaired thrombolytic activities.Here, we will present a 19-year-old woman who presented to the emergency department complaining of chest pain and shortness of breath for 3 days. The patient was quickly diagnosed with pulmonary embolism and inferior vena cava thrombosis as a complication of nephrotic syndrome, allowing prompt initiation of anticoagulant therapy. After 2 weeks of admission, the patient’s condition resolved, her laboratory results returned to almost normal and the patient was discharged with oral prednisolone, coumadin, atorvastatin, and ramipril. We aim to determine which is the likely cause of pulmonary embolism in patients with nephrotic syndrome.
Antitumor efficiency of the natural alkaloid berberine complexed with C60 fullerene in Lewis lung carcinoma in vitro and in vivo
Authors: Grebinyk Anna , Prylutska Svitlana , Grebinyk Sergii , Evstigneev Maxim , Krysiuk Iryna , Skaterna Tetiana , Horak Iryna , Sun Yanfang , Drobot Liudmyla , Matyshevska Olga , Prylutskyy Yuriy , Ritter Uwe , Frohme Marcus 
Published: August 2021

Abstract
Background
Berberine (Ber) is a herbal alkaloid with pharmacological activity in general and a high anticancer potency in particular. However, due to its low bioavailability, the difficulty in reaching a target and choosing the right dose, there is a need to improve approaches of Ber use in anticancer therapy. In this study, Ber, noncovalently bound to a carbon nanostructure C60 fullerene (C60) at various molar ratios of the components, was explored against Lewis lung carcinoma (LLC).

Methods
C60–Ber noncovalent nanocomplexes were synthesized in 1:2, 1:1 and 2:1 molar ratios. Ber release from the nanocomplexes was studied after prolonged incubation at different pH with the liquid chromatography–mass spectrometry analysis of free Ber content. Biological effects of the free and C60-complaxated Ber were studied in vitro towards LLC cells with phase-contrast and fluorescence microscopy, flow cytometry, MTT reduction, caspase activity and wound closure assays. The treatment with C60–Ber nanocomplex was evaluated in vivo with the LLC-tumored C57Bl mice. The mice body weight, tumor size, tumor weight and tumor weight index were assessed for four groups, treated with saline, 15 mg C60/kg, 7.5 mg Ber/kg or 2:1 C60-Ber nanocomplex (15 mg C60/kg, 7.5 mg Ber/kg).

Results
Ber release from C60–Ber nanocomplexes was promoted with medium acidification. LLC cells treatment with C60–Ber nanocomplexes was followed by enhanced Ber intracellular uptake as compared to free Ber. The cytotoxicity of the studied agents followed the order: free Ber < 1:2 < 1:1 < 2:1 C60–Ber nanocomplex. The potency of cytotoxic effect of 2:1 C60–Ber nanocomplex was confirmed by 21.3-fold decrease of IC50 value (0.8 ± 0.3 µM) compared to IC50 for free Ber (17 ± 2 µM). C60–Ber nanocomplexes induced caspase 3/7 activation and suppressed the migration activity of LLC cells. The therapeutic potency of 2:1 C60–Ber nanocomplex was confirmed in a mouse model of LLC. The tumor growth in the group treated with 2:1 C60–Ber nanocomplex is suppressed by approximately 50% at the end of experiment, while in the tumor-bearing group treated with free Ber no therapeutic effect was detected.

Conclusions
This study indicates that complexation of natural alkaloid Ber with C60 may be a novel therapeutic strategy against lung carcinoma.

Graphical abstract
The effect of home visits as an additional recruitment step on the composition of the final sample: a cross-sectional analysis in two study centers of the German National Cohort (NAKO)
Authors: Krist Lilian , Bedir Ahmed , Fricke Julia , Kluttig Alexander , Mikolajczyk Rafael 
Published: August 2021

Abstract
Background
Participation in epidemiologic studies has been declining over the last decades. In addition to postal invitations and phone calls, home visits can be conducted to increase participation. The aim of this study was therefore to evaluate the effects of home visits in terms of response increase and composition of the additionally recruited and final sample.

Methods
In the framework of the German National Cohort (NAKO) recruitment process, two of 18 study centers, Halle (Saale) and Berlin-Center, performed home visits as additional recruitment step after postal invitation and reminders. Response increase was calculated and differences between participants recruited via home visits and standard recruitment were examined. Proportions are presented as percentages with 95%-confidence intervals.

Results
In the general population in Halle, 21.3-22.8% participated after postal invitation and two reminders in the five assessed recruitment waves. The increase of the overall response was 2.8 percentage points (95%confidence interval: 1.9-4.0) for home visits compared to 2.4 percentage points (95%CI: 1.7-3.3) for alternatively sent third postal reminder. Participants recruited via home visits had similar characteristics to those recruited via standard recruitment. Among persons of Turkish descent in Berlin-Center site of the NAKO, home visits conducted by native speakers increased the participation of women, persons living together with their partner, were born in Turkey, had lower German language skills, lower-income, lower education, were more often smokers and reported more often diabetes and depression to a degree which changed overall estimates for this subsample.

Conclusions
As an additional recruitment measure in the general population, home visits increased response only marginally, and the through home visits recruited participants did not differ from those already recruited. Among persons with migration background, home visits by a native speaker increased participation of persons not reached by the standard recruitment, but the effects of using a native speaker approach could not be separated from the effect of home visits.
Long-term prognosis after endoscopic submucosal dissection for colorectal tumors in patients aged over 80 years
Authors: Nishimura Tomoyuki , Oka Shiro , Tanaka Shinji , Kamigaichi Yuki , Tamari Hirosato , Shimohara Yasutsugu , Okamoto Yuki , Inagaki Katsuaki , Matsumoto Kenta , Tanaka Hidenori , Yamashita Ken , Ninomiya Yuki , Kitadai Yasuhiko , Arihiro Koji , Chayama Kazuaki 
Published: August 2021

Abstract
Background
In Japan, endoscopic submucosal dissection (ESD) is standardized for large colorectal tumors. However, its validity in the elderly population is unclear. We aimed to evaluate the safety and efficacy of ESD for colorectal tumors in elderly patients aged over 80 years.

Methods
ESD was performed on 178 tumors in 165 consecutive patients aged over 80 years between December 2008 and December 2018. We retrospectively evaluated the clinicopathological characteristics and clinical outcomes of ESD. We also assessed the prognosis of 160 patients followed up for more than 12 months.

Results
The mean patient age was 83.7 ± 3.1 years. The number of patients with comorbidities was 100 (62.5%). Among all patients, 106 (64.2%) were categorized as class 1 or 2 according to the American Society of Anesthesiologists classification of physical status (ASA-PS), and 59 (35.8%) were classified as class 3. The mean procedure time was 97.7 ± 79.3 min. The rate of histological en bloc resection was 93.8% (167/178). Delayed bleeding in 11 cases (6.2%) and perforation in 7 cases (3.9%) were treated conservatively. The 5-year survival rate was 89.9%. No deaths from primary disease (mean follow-up time: 35.3 ± 27.5 months) were observed. Overall survival rates were significantly lower in the non-curative resection group that did not undergo additional surgery than in the curative resection group (P = 0.0152) and non-curative group that underwent additional surgery (P = 0.0259). Overall survival rates were higher for ASA-PS class 1 or 2 patients than class 3 patients (P = 0.0105). Metachronous tumors (> 5 mm) developed in 9.4% of patients.

Conclusions
ESD for colorectal tumors in patients aged over 80 years is safe. Colorectal cancer-associated deaths were prevented although comorbidities pose a high risk of poor prognosis.
Overexpression of SGLT2 in the kidney of a P. gingivalis LPS-induced diabetic nephropathy mouse model
Authors: Kajiwara Koichiro , Sawa Yoshihiko 
Published: August 2021

Abstract
Background
The overexpression of sodium-glucose cotransporter 2 (SGLT2) in diabetic kidneys has been reported. It has also been established that the diabetic glomerular endothelium expresses the toll-like receptors TLR2 and TLR4. The present study aims to examine the renal SGLT2 induction by the TLR2/4 ligand Porphyromonas (P.) gingivalis lipopolysaccharide (Pg-LPS) in mouse diabetic nephropathy.

Methods
Immunohistochemical study and tissue RT-PCR analyses were performed on mouse kidneys in streptozotocin (STZ)-induced diabetic ICR mice (STZ-ICR), in healthy ICR mice administered Pg-LPS (LPS-ICR), and in diabetic ICR mouse kidneys with Pg-LPS-induced nephropathy (LPS-STZ).

Results
In the quantitative analysis of blood sugar levels, the mean time to reach 600 mg/dl was shorter in the LPS-STZ than in the STZ-ICR kidneys. The rise in blood glucose levels was significantly steeper in the LPS-STZ than in the STZ-ICR kidneys. According to these data the LPS-STZ model suggests a marked glucose intolerance. The expression of SGLT2 was significantly stronger in the whole of the renal parenchyma of the LPS-STZ than in the LPS-ICR or in the STZ-ICR. The expression of SGLT2 was observed both in the renal tubules and around the renal tubules, and in the glomeruli of the LPS-STZ kidneys. In the analysis by tissue real-time PCR and cell ELISA, the expression of the SGLT2 gene and protein was significantly stronger in the LPS-STZ than in the LPS-ICR or in the STZ-ICR. There were no differences in the renal SGLT2 production in the LPS-ICR and the STZ-ICR kidneys.

Conclusions
Abnormally high renal expression of SGLT2 occurs in diabetic kidneys with P. gingivalis LPS. Periodontitis may be an exacerbating factor in diabetic nephropathy as well as in diabetes.
Clinical characteristics of middle-aged and older patients with MS treated with interferon beta-1b: post-hoc analysis of a 2-year, prospective, international, observational study
Authors: Patti Francesco , Penaherrera Javier Nicolas , Zieger Lorissa , Wicklein Eva-Maria 
Published: August 2021

Abstract
Background
Despite trends towards the increased age of patients living with multiple sclerosis (MS), little is known about the response of older adults with MS to disease-modifying therapies (DMTs). Thus, a post-hoc analysis was undertaken using data from a 2-year, international, non-interventional, prospective cohort study (NCT00787657; BEACON: BEtaferon prospective study on Adherence, COping and Nurse support) of patients above the age of 40 years with MS and starting interferon beta-1b (IFNB-1b) treatment within 6 months before study entry.

Methods
Middle-aged and older patients with MS were divided into two sub-groups: 41–50 years and > 50 years. Treatment with IFNB-1b started within 6 months before study entry. Patients were followed-up for a 2-year observation period. Assessments included disease history and course, annualised relapse rate (ARR), Expanded Disability Scale Score (EDSS), treatment adherence, Hospital Anxiety and Depression Scale (HADS), and adverse events (AE).

Results
At baseline, the intention-to-treat (ITT) population (n = 481) aged 41–50 years (n = 327) and > 50 years (n = 154), had mean (standard deviation [SD]) ages of 45.1 (2.8) and 56.2 (4.2) years, maximum age of 72 years, and duration of MS since onset of symptoms of 3.9 (5.2) and 5.9 (7.1) years, respectively. At baseline, the proportion of patients with relapsing–remitting MS (RRMS) was 96.3 and 94.9 %, and secondary progressive MS (SPMS) was 3.7 and 5.1 %, in the 41–50 and > 50 years sub-groups, respectively. The ARR in the 2 years before study start was 0.93 (0.48) and 0.86 (0.54) for the 41–50 and > 50 years groups, respectively, and decreased since study start to 0.20 (1.09) and 0.07 (0.37), respectively. The percentage of patients with anxiety and depression, as measured by HADS, were stable over the study period. Polypharmacy (five or more medications) was seen in 32.3 and 41.2 % of patients aged 41–50 and > 50 years. No unexpected AEs were reported.

Conclusions
This study provides observational data on patients between 40 and 72 years of age, suggesting that IFNB-1b can be an effective and well-tolerated treatment option in MS patients of advanced age.

Trial registration
ClinicalTrials.gov, NCT00787657.
Randomized phase II study of SOX+B-mab versus SOX+C-mab in patients with previously untreated recurrent advanced colorectal cancer with wild-type KRAS (MCSGO-1107 study)
Authors: Nishizawa Yujiro , Haraguchi Naotsugu , Kim Hirotoshi , Ide Yoshihito , Nakata Ken , Okamura Shu , Kudo Toshihiro , Satoh Taroh , Uemura Mamoru , Matsuda Chu , Mizushima Tsunekazu , Murata Kohei , Doki Yuichiro , Eguchi Hidetoshi 
Published: August 2021

Abstract
Background
Although chemotherapy for metastatic colorectal cancer (mCRC) has improved, the standard chemotherapy regimens for patients with RAS wild-type mCRC remain debated. This study aimed to compare S-1 and oxaliplatin (SOX) + bevacizumab (B-mab) with SOX + cetuximab (C-mab) in patients with previously untreated recurrent advanced CRC with wild-type KRAS.

Methods
This randomized phase II, open-label, multicenter study compared the efficacy and safety of SOX+B-mab with SOX+C-mab in patients with previously untreated advanced CRC with wild-type KRAS. Between February 2012 and October 2016, 45 patients were enrolled.

Results
Overall response rates were 59.1 and 43.5% (p = 0.29) and disease control rates were 90.9 and 91.3% (p = 0.96) in the SOX+B-mab and SOX+C-mab groups, respectively. Median overall survival (OS) was 25.3 and 15.5 months (HR = 0.607, p = 0.167) and median progression-free survival (PFS) were 11.7 and 5.5 months (HR = 0.558, p = 0.077) in the SOX+B-mab and SOX+C-mab groups, respectively. The OS and PFS of patients with early tumor shrinkage (ETS) were not significantly different in the SOX+B-mab group. However, they were significantly better when ETS was ≥20 in the SOX+C-mab group (p = 0.032 and p = 0.003, respectively).

Conclusions
The efficacy and safety of SOX+B-mab and SOX+C-mab for wild-type KRAS recurrent advanced CRC as first-line chemotherapy were almost the same. Consideration of the treatment strategy based on ETS may improve patient prognosis, especially in patients receiving the SOX+C-mab regimen.

Trial registration
UMIN Clinical Trials Registry (UMIN000006706).
Date of registration: NOV/11/2011.
URL of trial registry record:
https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000007920