bluuebunny/crossref_metadata_2025_split huggingface dataset:
Childhood head trauma and the risk of childhood brain tumours: A case‐control study in Ontario, Canada
Authors: Cheng Sierra , McLaughlin John R. , Brown M. Catherine , Al‐Sawaihey Hamad , Rutka James , Bouffet Eric , Hawkins Cynthia , Cairney A. Elizabeth , Ranger Adrianna , Fleming Adam J. , Johnston Donna , Greenberg Mark , Malkin David , Hung Rayjean J. 
Published: September 2021

AbstractHead trauma in early childhood has been hypothesized as a potential risk factor for childhood brain tumours (CBTs). However, head trauma has not been extensively studied in the context of CBTs and existing studies have yielded conflicting results. A population‐based and hospital‐based case‐control study of children 0 to 15 years with newly diagnosed CBTs from 1997 to 2003 recruited across Ontario through paediatric oncology centres was conducted. Controls were frequency‐matched with cases by age, sex and geographical region. The association was assessed based on multivariable logistic regressions, accounting for child's age, sex, ethnicity, highest level of maternal education and maternal pack‐years of smoking during the pregnancy. Analyses were conducted separately based on age of first head trauma, sex and histology. A latency period analysis was conducted. Overall, based on 280 cases and 919 controls, CBTs were not significantly associated with previous history of head trauma (OR 1.34, 95% CI 0.96, 1.86), head trauma severity, number of head injuries, or head or neck X‐rays or computed tomography (CT) examinations. Results were consistent across sexes and histological subtypes. However, head trauma within the first year of life was significantly associated with CBTs (OR 2.00, 95% CI 1.01, 3.98), but the association diminished when adjusted for X‐ray or CT occurring during the same time period (OR 1.62, 95% CI 0.75, 3.49), albeit limited sample size. Overall, no association was observed between head trauma and CBTs among all children, while head trauma occurring within first year of life may warrant further investigation in future research.
Survival outcomes associated with completion of adjuvant oxaliplatin‐based chemotherapy for stage III colon cancer: A national population‐based study
Authors: Boyle Jemma M. , Kuryba Angela , Cowling Thomas E. , van der Meulen Jan , Fearnhead Nicola S. , Walker Kate , Braun Michael S. , Aggarwal Ajay 
Published: September 2021

AbstractThe impact of cycle completion rates of oxaliplatin‐based adjuvant chemotherapy for stage III colon cancer in real‐world practice is unknown. We assessed its impact, and that of treatment modification, on 3‐year cancer‐specific mortality. Four thousand one hundred and forty‐seven patients with pathological stage III colon cancer undergoing major resection from 2014 to 2017 in the English National Health Service were included. Chemotherapy data came from linked national administrative datasets. Competing risk regression analysis for 3‐year cancer‐specific mortality was performed according to completion of <6, 6‐11, or 12 5‐fluoropyrimidine and oxaliplatin (FOLFOX) cycles, or <4, 4‐7, or 8 capecitabine and oxaliplatin (CAPOX) cycles, adjusted for patient, tumour and hospital‐level characteristics. Median age was 64 years. Thirty‐two per cent of patients had at least one comorbidity. Forty‐two per cent of patients had T4 disease, and 40% had N2 disease. Compared to completion of 12 FOLFOX cycles, cancer‐specific mortality was higher in patients completing <6 cycles [subdistribution hazard ratios (sHR) 2.17; 95% CI 1.56‐3.03] or 6‐11 cycles (sHR 1.40; 95% CI 1.09‐1.78) (P < .001). Compared to completion of 8 CAPOX cycles, cancer‐specific mortality was higher in patients completing <4 cycles (sHR 2.02; 95% CI 1.53‐2.67) or 4‐7 cycles (sHR 1.63; 95% CI 1.27‐2.10) (P < .001). Dose reduction and early oxaliplatin discontinuation did not impact mortality in patients completing all cycles. Completion of all cycles of chemotherapy was associated with improved cancer‐specific survival in real‐world practice. Poor prognostic factors may have affected findings, however, patients completing <50% of cycles had poor outcomes. Clinicians may wish to facilitate completion with treatment modification in those able to tolerate it.
A transcriptome‐wide association study identifies novel candidate susceptibility genes for prostate cancer risk
Authors: Liu Duo , Zhu Jingjing , Zhou Dan , Nikas Emily G. , Mitanis Nikos T. , Sun Yanfa , Wu Chong , Mancuso Nicholas , Cox Nancy J. , Wang Liang , Freedland Stephen J. , Haiman Christopher A. , Gamazon Eric R. , Nikas Jason B. , Wu Lang 
Published: September 2021

AbstractA large proportion of heritability for prostate cancer risk remains unknown. Transcriptome‐wide association study combined with validation comparing overall levels will help to identify candidate genes potentially playing a role in prostate cancer development. Using data from the Genotype‐Tissue Expression Project, we built genetic models to predict normal prostate tissue gene expression using the statistical framework PrediXcan, a modified version of the unified test for molecular signatures and Joint‐Tissue Imputation. We applied these prediction models to the genetic data of 79 194 prostate cancer cases and 61 112 controls to investigate the associations of genetically determined gene expression with prostate cancer risk. Focusing on associated genes, we compared their expression in prostate tumor vs normal prostate tissue, compared methylation of CpG sites located at these loci in prostate tumor vs normal tissue, and assessed the correlations between the differentiated genes' expression and the methylation of corresponding CpG sites, by analyzing The Cancer Genome Atlas (TCGA) data. We identified 573 genes showing an association with prostate cancer risk at a false discovery rate (FDR) ≤ 0.05, including 451 novel genes and 122 previously reported genes. Of the 573 genes, 152 showed differential expression in prostate tumor vs normal tissue samples. At loci of 57 genes, 151 CpG sites showed differential methylation in prostate tumor vs normal tissue samples. Of these, 20 CpG sites were correlated with expression of 11 corresponding genes. In this TWAS, we identified novel candidate susceptibility genes for prostate cancer risk, providing new insights into prostate cancer genetics and biology.
FIGO good practice recommendations on cervical cerclage for prevention of preterm birth
Authors: Shennan Andrew , Story Lisa , Jacobsson Bo , Grobman William A. ,   the FIGO Working Group for Preterm Birth
Published: September 2021

AbstractCervical cerclage is an intervention which when given to the right women can prevent preterm birth and second‐trimester fetal losses. A history‐indicated cerclage should be offered to women who have had three or more preterm deliveries and/or mid‐trimester losses. An ultrasound‐indicated cerclage should be offered to women with a cervical length <25 mm if they have had one or more spontaneous preterm birth and/or mid‐trimester loss. In high‐risk women who have not had a previous mid‐trimester loss or preterm birth, an ultrasound‐indicated cerclage does not have a clear benefit in women with a short cervix. However, for twins, the advantage seems more likely at shorter cervical lengths (<15 mm). In women who present with exposed membranes prolapsing through the cervical os, a rescue cerclage can be considered on an individual case basis, taking into account the high risk of infective morbidity to mother and baby. An abdominal cerclage can be offered in women who have had a failed cerclage (delivery before 28 weeks after a history or ultrasound‐indicated [but not rescue] cerclage). If preterm birth has not occurred, removal is considered at 36–37 weeks in women anticipating a vaginal delivery.
FIGO good practice recommendations on the use of prenatal corticosteroids to improve outcomes and minimize harm in babies born preterm
Authors: Norman Jane , Shennan Andrew , Jacobsson Bo , Stock Sarah J. ,   the FIGO Working Group for Preterm Birth
Published: September 2021

AbstractFor women with a singleton or a multiple pregnancy in situations where active neonatal care is appropriate, and for whom preterm birth is anticipated between 24 and 34 weeks of gestation, one course of prenatal corticosteroids should ideally be offered 18 to 72 h before preterm birth is expected to improve outcomes for the baby. However, if preterm birth is expected within 18 h, prenatal corticosteroids should still be administered. One course of corticosteroids includes two doses of betamethasone acetate/phosphate 12 mg IM 24 h apart, or two doses of dexamethasone phosphate 12 mg IM 24 h apart. In women in whom preterm birth is expected within 72 h and who have had one course of corticosteroids more than a week previously, one single additional course of prenatal corticosteroids could be given at risk of imminent delivery. Prenatal corticosteroids should not be offered routinely to women in whom late preterm birth between 34 and 36 weeks is anticipated. In addition, prenatal corticosteroids should not be given routinely before cesarean delivery at term. Neither should prenatal corticosteroids be given “just in case”. Instead, prenatal steroid administration should be reserved for women for whom preterm birth is expected within no more than 7 days, based on the woman's symptoms or an accurate predictive test.
FIGO good practice recommendations on delayed umbilical cord clamping
Authors: Bianchi Ana , Jacobsson Bo , Mol Ben W. ,   the FIGO Working Group for Preterm Birth
Published: September 2021

AbstractDelayed cord clamping in the first minute in preterm infants born before 34 weeks of gestation improves neonatal hematologic measures and may reduce mortality without increasing any other morbidity. In term‐born babies, it also seems to improve both the short‐ and long‐term outcomes and shows favorable scores in fine motor and social domains. However, there is insufficient evidence to show what duration of delay is best. The current evidence supports not clamping the cord before 30 seconds for preterm births. Future trials could compare different lengths of delay. Until then, a period of 30 seconds to 3 minutes seems justified for term‐born babies.
FIGO staging for carcinoma of the vulva: 2021 revision
Authors: Olawaiye Alexander B. , Cotler Joseph , Cuello Mauricio A. , Bhatla Neerja , Okamoto Aikou , Wilailak Sarikapan , Purandare Chittaranjan N. , Lindeque Gerhard , Berek Jonathan S. , Kehoe Sean 
Published: September 2021

AbstractTo revise the FIGO staging for carcinoma of the vulva using a new approach that involves analyses of prospectively collected data. The FIGO Committee for Gynecologic Oncology reviewed the recent literature to gain an insight into the impact of the 2009 vulvar cancer staging revision. The Committee resolved to revise the staging with a goal of simplification and actively collaborated with the United States National Cancer Database to analyze prospectively collected data on carcinoma of the vulva. Many tumor characteristics were collected for all stages of vulvar cancer treated between 2010 and 2017. Statistical analysis was performed with SAS software. Overall survival was estimated based on tumor characteristics. Log‐rank and Wilcoxon tests were used to analyze overall survival similarities between and within groups of tumor characteristics. Characteristics with similar survivals were then grouped into the same stages and substages. Kaplan–Meier overall survival curves were generated for the resulting stages and substages. There were 12 063 cases with available data. The resulting new staging for carcinoma of the vulva has two substages in Stage I, no substage in Stage II, three substages in Stage III, and two substages in Stage IV. The Kaplan–Meier overall survival curves showed clear separation between stages and substages. The 2021 vulvar cancer staging is the first from the FIGO Committee for Gynecologic Oncology to be derived from data analyses. This revision has a new definition for depth of invasion, uses the same definition for lymph node metastases utilized in cervical cancer, and allows findings from cross‐sectional imaging to be incorporated into vulvar cancer staging. The 2021 FIGO staging for carcinoma of the vulva is data‐derived, validated, and much simpler than earlier revisions.
Successful treatment with immunoadsorption therapy in four patients with severe and refractory anti‐N‐methyl‐D‐aspartate receptor encephalitis
Authors: Yang Yu , Zhang Bingjun , Li Min , Li Jing 
Published: September 2021

AbstractThere is still no optimal treatment for patients with severe anti‐N‐methyl‐D‐aspartate receptor (NMDAR) encephalitis refractory to first‐line therapy (including intravenous methylprednisolone [IVMP] and intravenous immunoglobulin [IVIG]). A small study has shown that immunoadsorption (IA) is effective in treating anti‐NMDAR encephalitis. However, the effectiveness and safety of IA in the treatment of patients with refractory and severe anti‐NMDAR encephalitis is not fully known. Four patients with severe anti‐NMDAR encephalitis are reported, which were refractory to the first‐line immunotherapy including IVMP and IVIG. Immunoadsorption is performed during the fulminant stage of disease, and the effectiveness and safety of IA are assessed. The modified Rankin Scale (mRS) is used to assess neurological conditions before and after IA. Four patients with the most severe form of anti‐NMDAR encephalitis (two with teratoma and two with unknown origin) did not respond to one or more rounds of IVMP plus IVIG. They all required intensive care unit (ICU) support including long‐term mechanical ventilation, and thus developed ICU‐related complications. Gradual and steady improvement was observed after IA treatment. Except for mild hypotension in patient 1, no other adverse events were observed during IA. Two patients had good early overall recovery on discharge. The other two patients had a good outcome with mRS of 2 at the 12‐month follow‐up. This small case series suggests that IA may be an effective treatment option to accelerate the recovery of patients with severe and refractory anti‐NMDAR encephalitis.
Biochemical strategies of E3 ubiquitin ligases target viruses in critical diseases
Authors: Dubey Ankur R. , Jagtap Yuvraj A. , Kumar Prashant , Patwa Som M. , Kinger Sumit , Kumar Amit , Singh Sarika , Prasad Amit , Jana Nihar R. , Mishra Amit 
Published: September 2021

AbstractViruses are known to cause various diseases in human and also infect other species such as animal plants, fungi, and bacteria. Replication of viruses depends upon their interaction with hosts. Human cells are prone to such unwanted viral infections. Disintegration and reconstitution require host machinery and various macromolecules like DNA, RNA, and proteins are invaded by viral particles. E3 ubiquitin ligases are known for their specific function, that is, recognition of their respective substrates for intracellular degradation. Still, we do not understand how ubiquitin proteasome system‐based enzymes E3 ubiquitin ligases do their functional interaction with different viruses. Whether E3 ubiquitin ligases help in the elimination of viral components or viruses utilize their molecular capabilities in their intracellular propagation is not clear. The first time our current article comprehends fundamental concepts and new insights on the different viruses and their interaction with various E3 Ubiquitin Ligases. In this review, we highlight the molecular pathomechanism of viruses linked with E3 Ubiquitin Ligases dependent mechanisms. An enhanced understanding of E3 Ubiquitin Ligase‐mediated removal of viral proteins may open new therapeutic strategies against viral infections.
Association of serum adiponectin and leptin levels with renal function in kidney transplant recipients with or without new‐onset diabetes after transplantation
Authors: Pham Vu Thuy , Can Van Mao , Dang Thanh Chung , Nguyen Minh Tuan , Nguyen Trung Kien , Nguyen Duy Toan , Do Quyet , Tran Viet Tien , Le Viet Thang 
Published: September 2021

AbstractPurposeTo evaluate serum adiponectin and leptin concentration in new‐onset diabetes after transplantation (NODAT) and non‐NODAT patients and association with renal function in kidney transplant recipients (KTRs).Patients and methodsA study of 314 consecutive adults KTRs divided into four groups: 236 individuals without NODAT who had renal insufficiency (RI; n = 56) or normal renal function (n = 180) and 78 patients with NODAT who had RI (n = 17) or normal renal function (n = 61). NODAT was diagnosed based on venous fasting blood glucose or HbA1c with the criteria of the American Diabetes Association. Renal insufficiency was defined according to KDOQI 2002 guidelines.ResultsIn the NODAT group, the median level of serum adiponectin was lower than that of non‐NODAT one (30 µg/ml vs 37.15 µg/ml, p < 0.001); in contrast, the median leptin concentration was higher (4.27 ng/ml vs 4.05 ng/ml, p = 0.024). In the RI group, both median serum adiponectin and leptin levels were higher than those of non‐RI one (Adiponectin: 40.01 µg/ml vs 33.7 µg/ml; Leptin: 4.51 ng/ml vs 3.91 ng/ml, p < 0.001 both). We found that BMI was related to both adiponectin and leptin levels in both NODAT, non‐NODAT, and all subject groups, based on univariate and multivariate linear regression analysis.ConclusionNew‐onset diabetes after transplantation, BMI, and renal insufficiency were affected to the serum level of adiponectin and leptin in KTRs.
Formation of a protein corona on the surface of extracellular vesicles in blood plasma
Authors: Tóth Eszter Á. , Turiák Lilla , Visnovitz Tamás , Cserép Csaba , Mázló Anett , Sódar Barbara W. , Försönits András I. , Petővári Gábor , Sebestyén Anna , Komlósi Zsolt , Drahos László , Kittel Ágnes , Nagy György , Bácsi Attila , Dénes Ádám , Gho Yong Song , Szabó‐Taylor Katalin É. , Buzás Edit I. 
Published: September 2021

AbstractIn this study we tested whether a protein corona is formed around extracellular vesicles (EVs) in blood plasma. We isolated medium‐sized nascent EVs of THP1 cells as well as of Optiprep‐purified platelets, and incubated them in EV‐depleted blood plasma from healthy subjects and from patients with rheumatoid arthritis. EVs were subjected to differential centrifugation, size exclusion chromatography, or density gradient ultracentrifugation followed by mass spectrometry. Plasma protein‐coated EVs had a higher density compared to the nascent ones and carried numerous newly associated proteins. Interactions between plasma proteins and EVs were confirmed by confocal microscopy, capillary Western immunoassay, immune electron microscopy and flow cytometry. We identified nine shared EV corona proteins (ApoA1, ApoB, ApoC3, ApoE, complement factors 3 and 4B, fibrinogen α‐chain, immunoglobulin heavy constant γ2 and γ4 chains), which appear to be common corona proteins among EVs, viruses and artificial nanoparticles in blood plasma. An unexpected finding of this study was the high overlap of the composition of the protein corona with blood plasma protein aggregates. This is explained by our finding that besides a diffuse, patchy protein corona, large protein aggregates also associate with the surface of EVs. However, while EVs with an external plasma protein cargo induced an increased expression of TNF‐α, IL‐6, CD83, CD86 and HLA‐DR of human monocyte‐derived dendritic cells, EV‐free protein aggregates had no effect. In conclusion, our data may shed new light on the origin of the commonly reported plasma protein ‘contamination’ of EV preparations and may add a new perspective to EV research.
Effect of modulating glutamate signaling on myelinating oligodendrocytes and their development—A study in the zebrafish model
Authors: Turan Funda , Yilmaz Öznur , Schünemann Lena , Lindenberg Tobias T. , Kalanithy Jeshurun C. , Harder Alexander , Ahmadi Shiva , Duman Türker , MacDonald Ryan B. , Winter Dominic , Liu Changsheng , Odermatt Benjamin 
Published: September 2021

AbstractMyelination is crucial for the development and maintenance of axonal integrity, especially fast axonal action potential conduction. There is increasing evidence that glutamate signaling and release through neuronal activity modulates the myelination process. In this study, we examine the effect of manipulating glutamate signaling on myelination of oligodendrocyte (OL) lineage cells and their development in zebrafish (zf). We use the “intensity‐based glutamate‐sensing fluorescent reporter” (iGluSnFR) in the zf model (both sexes) to address the hypothesis that glutamate is implicated in regulation of myelinating OLs. Our results show that glial iGluSnFR expression significantly reduces OL lineage cell number and the expression of myelin markers in larvae (zfl) and adult brains. The specific glutamate receptor agonist, L‐AP4, rescues this iGluSnFR effect by significantly increasing the expression of the myelin‐related genes, plp1b and mbpa, and enhances myelination in L‐AP4‐injected zfl compared to controls. Furthermore, we demonstrate that degrading glutamate using Glutamat‐Pyruvate Transaminase (GPT) or the blockade of glutamate reuptake by L‐trans‐pyrrolidine‐2,4‐dicarboxylate (PDC) significantly decreases myelin‐related genes and drastically declines myelination in brain ventricle‐injected zfl. Moreover, we found that myelin‐specific ClaudinK (CldnK) and 36K protein expression is significantly decreased in iGluSnFR‐expressing zfl and adult brains compared to controls. Taken together, this study confirms that glutamate signaling is directly required for the preservation of myelinating OLs and for the myelination process itself. These findings further suggest that glutamate signaling may provide novel targets to therapeutically boost remyelination in several demyelinating diseases of the CNS.
Subanalgesic morphine doses augment fentanyl analgesia by interacting with delta opioid receptors in male rats
Authors: Barker Katherine E. , Lecznar Alynn J. , Schumacher Jill M. , Morris Jeffrey S. , Gutstein Howard B. 
Published: September 2021

AbstractOpioids are commonly used for the treatment of postoperative and post‐traumatic pain; however, their therapeutic effectiveness is limited by undesirable and life‐threatening side effects. Researchers have long attempted to develop opioid co‐administration therapies that enhance analgesia, but the complexity of opioid analgesia and our incomplete mechanistic understanding has made this a daunting task. We discovered that subanalgesic morphine doses (100 ng/kg–10 µg/kg) augmented the acute analgesic effect of fentanyl (20 µg/kg) following subcutaneous drug co‐administration to male rats. In addition, administration of equivalent drug ratios to naïve rat spinal cord membranes induced a twofold increase in G protein activation. The rate of GTP hydrolysis remained unchanged. We demonstrated that these behavioral and biochemical effects were mediated by the delta opioid receptor (DOP). Subanalgesic doses of the DOP‐selective agonist SNC80 also augmented the acute analgesic effect of fentanyl. Furthermore, co‐administration of the DOP antagonist naltrindole with both fentanyl‐morphine and fentanyl‐SNC80 combinations prevented augmentation of both analgesia and G protein activation. The mu opioid receptor (MOP) antagonist cyprodime did not block augmentation. Confocal microscopy of the substantia gelatinosa of rats treated with fentanyl, subanalgesic morphine, or this combination showed that changes in MOP internalization did not account for augmentation effects. Together, these findings suggest that augmentation of fentanyl analgesia by subanalgesic morphine is mediated by increased G protein activation resulting from a synergistic interaction between or heterodimerization of MOPs and DOPs. This finding is of great therapeutic significance because it suggests a strategy for the development of DOP‐selective ligands that can enhance the therapeutic index of clinically used MOP drugs.