bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exome sequencing identifies SLIT2 variants in primary CNS lymphoma
Authors: Kaulen Leon D. , Erson‐Omay E. Zeynep , Henegariu Octavian , Karschnia Philipp , Huttner Anita , Günel Murat , Baehring Joachim M. 
Published: January 2021

SummarySLIT2 constitutes a known tumour suppressor gene, which has not yet been implicated in the pathogenesis of primary central nervous system lymphoma (PCNSL). Performing exome sequencing on paired blood and tumour DNA samples from six treatment‐naïve PCNSL patients, we identified novel SLIT2 variants (p.N63S, p.T590M, p.T732S) that were associated with shorter progression‐free survival in our cohort and shorter overall survival in a large validation cohort of lymphoid malignancies from the cBio Cancer Genomics Portal. WNT‐ and NF‐κB‐reporter luciferase assays suggest detected alterations are loss‐of‐function variants. Given the possible prognostic implications, the role of SLIT2 in PCNSL pathogenesis and progression warrants further investigation.
The long‐term outcome of urethrotomy for primary urethral strictures: a population‐based analysis
Authors: Eredics Klaus , Röthlin Florian , Wachabauer David , Sevcenco Sabina , Marszalek Martin , Mock Karl , Madersbacher Stephan 
Published: January 2021

ObjectiveTo determine the long‐term outcome of endoscopic urethrotomy for primary urethral strictures based on a population‐based approach.Patients and MethodsWe analysed a nationwide database of all patients with urethral stricture disease who underwent endoscopic urethrotomy as a primary intervention between January 2006 and December 2007. All patients were followed individually for 7–9 years. Frequencies and types of surgical re‐interventions were documented. Repeat surgical interventions were stratified into three treatment types: urethrotomy, urethroplasty, and end‐to‐end urethral anastomosis.ResultsA total of 1203 men underwent urethrotomy during the index period. The median (SD, range) patient age was 63 (15.7, 20–85) years. A total of 136 patients (11%) died during follow‐up. Within the follow‐up period, 932 patients (78%) received no further surgical re‐intervention for recurrent disease, and 176 patients (14.6%) required one, 53 (4.5%) two, and 41 (3.4%) three or more procedures. The mean number of re‐interventions was 1.5/patient and the lowest re‐intervention rate was in patients aged ≥80 years (13.9%). In 236 cases (68%) at least one repeat urethrotomy was performed. An open reconstruction was performed in 87 cases (32%), with urethroplasty in 21 patients (24%), and end‐to‐end anastomosis in 66 patients (76%). The mean interval until re‐intervention was 29.5 months.ConclusionsThis long‐term population‐based study suggests that the invasive re‐treatment rate in men following initial urethrotomy is 22% within 8 years and lowest in the advanced age cohort.
A novel oncotherapy strategy: Direct thrombin inhibitors suppress progression, dissemination and spontaneous metastasis in non‐small cell lung cancer
Authors: Zhao Bing , Wu Mengfang , Hu Zhihuang , Wang Tianfa , Yu Jinchao , Ma Yixin , Wang Qi , Zhang Yanling , Chen Di , Li Tianyu , Li Yaran , Yu Min , Wang Huijie , Mo Wei 
Published: January 2021

Background and PurposeCancer cachexia and cancer‐associated thrombosis are potentially fatal outcomes of advanced cancer. Nevertheless, thrombin expression in non‐small cell lung cancer (NSCLC) primary tumour tissues and the association between prognosis of NSCLC patients remain largely unknown.Experimental ApproachClinical pathological analysis was performed to determine the relationship between thrombin and tumour progression. Effects of r‐hirudin and direct thrombin inhibitor peptide (DTIP) on cancer progression were evaluated. Western blotting, immunohistochemistry, and immunofluorescence were used to explore the inhibition mechanism of r‐hirudin and DTIP. The therapeutic effect of the combination of DTIP and chemotherapy was determined.Key ResultsThrombin expression in NSCLC tissues was closely related to clinicopathological features and the prognosis of patients. Thrombin deficiency inhibited tumour progression. The novel thrombin inhibitors, r‐hirudin and DTIP, inhibited cell invasion and metastasis in vitro. They inhibited tumour growth and metastasis in orthotopic lung cancer model, inhibited cell invasion, and prolonged survival after injection of tumour cells via the tail vein. They also inhibited angiogenesis and spontaneous metastases from subcutaneously inoculated tumours. The promotion by thrombin of invasion and metastasis was abolished in PAR‐1‐deficient NSCLC cells. r‐hirudin and DTIP inhibited tumour progression through the thrombin‐PAR‐1‐mediated RhoA and NF‐κB signalling cascades via inhibiting MMP9 and IL6 expression. DTIP potentiated chemotherapy‐induced growth and metastatic inhibition and inhibited chemotherapy‐induced resistance in mice.Conclusions and ImplicationsThrombin makes a substantial contribution, together with PAR‐1, to NSCLC malignancy. The anti‐coagulants, r‐hirudin and DTIP, could be used in anti‐tumour therapy and a combination of DTIP and chemotherapy might improve therapeutic effects.
The impact of molecular profile on the lymphatic spread pattern in stage III colon cancer
Authors: Song Jihyung , Kataoka Kozo , Yamada Takeshi , Shiozawa Manabu , Sonoyama Tomohiro , Beppu Naohito , Ueda Koji , Kuriyama Sho , Kanazawa Akiyoshi , Ikeda Masataka , Ceelen Wim 
Published: January 2021

AbstractThe anatomical spread of lymph node (LN) metastasis is of practical importance in the surgical management of colon cancer (CC). We examined the effect of KRAS, BRAF, and microsatellite instability (MSI) on LN count and anatomical spread pattern in stage III CC. We determined KRAS, BRAF, and MSI status from stage III CC patients. Biomarker status was correlated with LN count and anatomical spread pattern, which was classified as sequential or skipped. Relapse‐free survival (RFS) was estimated using Kaplan‐Meier method, and correlations were assessed using log‐rank and Cox regression analyses. We analyzed 369 stage III CC patients. The proportion of KRAS mutant (mt), BRAF mt, and MSI‐high (H) were 44.2% (163/344), 6.8% (25/344), and 6.8% (25/344), respectively. The mean number of metastatic LN was higher in microsatellite‐stable (MSS) compared with MSI patients (3.5 vs. 2.7, P = .0406), although no differences were observed in accordance with KRAS or BRAF status. Interestingly, patients with BRAF mt and MSI‐H were less likely to harbor skipped metastatic LN (9.3% vs 20% and 4% vs 10.5% compared with BRAF wild‐type (wt) and MSS, respectively), but KRAS status did not predict anatomical spread pattern. Patients with KRAS wt and MSI‐H showed superior RFS compared with KRAS mt and MSS patients, respectively, whereas BRAF status did not affect RFS. Differences exist in the anatomical pattern of invaded LN in accordance with the molecular status of stage III CC. Patients with MSI‐H CC have less invaded and skipped LN, suggesting that a tailored surgical approach is possible.
TARBP2 promotes tumor angiogenesis and metastasis by destabilizing antiangiogenic factor mRNAs
Authors: Zhou Meicen , Lu Wenbao , Li Bingwei , Liu Xueting , Li Ailing 
Published: January 2021

AbstractTumor angiogenesis is a crucial step in the further growth and metastasis of solid tumors. However, its regulatory mechanism remains unclear. Here, we showed that TARBP2, an RNA‐binding protein, played a role in promoting tumor‐induced angiogenesis both in vitro and in vivo through degrading the mRNAs of antiangiogenic factors, including thrombospondin1/2 (THBS1/2), tissue inhibitor of metalloproteinases 1 (TIMP1), and serpin family F member 1 (SERPINF1), by targeting their 3′untranslated regions (3′UTRs). Overexpression of TARBP2 promotes tumor cell–induced angiogenesis, while its knockdown inhibits tumor angiogenesis. Clinical cohort analysis revealed that high expression level of TARBP2 was associated with poor survival of lung cancer and breast cancer patients. Mechanistically, TARBP2 physically interacts with the stem‐loop structure located in the 3′UTR of antiangiogenic transcripts, leading to mRNA destabilization by the dsRNA‐binding domains 1/2 (dsRBDs1/2). Notably, the expression level of TARBP2 in human tumor tissue is negatively correlated with the expression of antiangiogenic factors, including THBS1/2, and brain‐specific angiogenesis inhibitor 1 (BAI1). Moreover, TARBP2 expression is strongly associated with tumor angiogenesis in a group of human lung cancer samples. Collectively, our results highlight that TARBP2 is a novel tumor angiogenesis regulator that could promote tumor angiogenesis by selectively downregulating antiangiogenic gene expression.
Children Persist Less When Adults Take Over
Authors: Leonard Julia A. , Martinez Dominique N. , Dashineau Samantha C. , Park Anne T. , Mackey Allyson P. 
Published: January 2021

Children need to learn to persist through challenges, yet adults sometimes step in to solve problems for them. Here, we looked at how adult taking over related to children’s persistence. In an observational study (N = 34, ages 4–8), we found that parents who took over more often during a challenging puzzle task rated their children as dispositionally less persistent. To establish whether taking over can cause reduced persistence, we ran two preregistered experiments (N = 150, ages 4–5). Children assigned to a taking over condition persisted less on a subsequent task compared to those in a teaching or a baseline condition. Reframing the context did not ameliorate the negative impact of taking over. The results suggest that taking over impairs children’s persistence.
Pre‐ and postoperative 68Ga‐DOTATOC positron emission tomography for hormone‐secreting pituitary neuroendocrine tumours
Authors: Tjörnstrand Axel , Casar‐Borota Olivera , Heurling Kerstin , Schöll Michael , Gjertsson Peter , Ragnarsson Oskar , Filipsson Nyström Helena 
Published: January 2021

AbstractObjectivesSomatostatin receptors (SSTRs) are potential targets for detecting pituitary neuroendocrine tumours (PitNETs) that can be visualized effectively with 68Ga‐labelled PET tracers. With this study, we have evaluated the diagnostic properties of such a tracer, 68Ga‐DOTATOC, in patients with hormone‐producing PitNETs before and after surgery.Design/MethodsThis prospective case‐control study presents preoperative positron emission tomography (PET) and histopathological data in 18 patients with somatotroph (n = 8), corticotroph (n = 7) and thyrotroph (n = 3) PitNETs. Patients were scanned pre‐ and postoperatively with 68Ga‐DOTATOC PET. For the postoperative part of the study, patients with gonadotroph tumours (n = 7) were also included. Fifteen pituitary healthy controls underwent the same protocol once. The maximum standard uptake value (SUVmax) was analysed in manually outlined regions around the tumour in patients and around the pituitary gland in controls. specimens were collected during surgery in subjects for assessment of adenohypophyseal tumour cell type and the SSTR expression.ResultsThyrotroph tumours showed higher uptake (median SUVmax 41.1; IQR 37.4‐60.0) and corticotroph tumours lower uptake (SUVmax 6.8; 2.6‐9.3) than normal pituitary gland (SUVmax 13.8; 12.1‐15.5). The uptake in somatotroph tumours (SUVmax 15.9; 11.6‐19.7) was similar to the uptake in the pituitary gland. There was a strong correlation between SUVmax and SSTR2 expression (r = .75 (P < .01)). In the postoperative evaluation, PET was able to correlate tracer uptake with biochemical cure and noncure in patients with an abnormal postoperative magnetic resonance image and a preoperative tumour uptake SUVmax > 13.8.Conclusions68Ga‐DOTATOC PET can be used to detect thyrotroph tumours in the pre‐ and postoperative imaging assessment. Corticotroph tumours had a significantly lower uptake compared to the pituitary gland but without a distinct increased tumour uptake the clinical postoperative value is limited.
Thyroid eye disease: Redefining its management—A review
Authors: Jain Amy P. , Jaru‐Ampornpan Pimkwan , Douglas Raymond S. 
Published: January 2021

AbstractThyroid eye disease (TED) is a debilitating, vision threatening disease that dramatically alters patients' quality of life. Until recently, the management of TED is a long arduous course with supportive therapy, followed by an extensive surgical treatment plan to reverse the disease endpoints. Teprotumumab offers an early, safe therapeutic intervention to help reverse disease end points such as diplopia and proptosis and improve quality of life.
Improving clinical practice in ENT: Lessons learnt from the COVID‐19 pandemic
Authors: Tysome James R. 
Published: January 2021

AbstractDuring the COVID‐19 pandemic, the ENT community has demonstrated strong clinical leadership, adaptability to rapid change, enhanced clinical pathways and local networks, widespread use of digital technology for consultation and teaching and redirection of research programmes. These have permanently changed the way we work and, when the current global pandemic improves as COVID‐19 infections drop and vaccination programmes are rolled out, we should ensure that the positive changes that have been made are embedded in clinical practice to improve patient care.
Urinary dysfunction after colorectal cancer treatment and its impact on quality of life – a national cross‐sectional study in women
Authors: Sinimäki Saija , Elfeki Hossam , Kristensen Marianne Højsgaard , Laurberg Søren , Emmertsen Katrine J. 
Published: January 2021

AbstractAimThe aim of this study was to investigate urinary dysfunction and its impact on the quality of life of colorectal cancer survivors. We also wanted to identify the risk factors for impaired urinary function.MethodA national cross‐sectional study was performed including patients treated for colorectal cancer between 2001 and 2014. Patients answered questionnaires regarding urinary function and quality of life, including the International Consultation on Incontinence Questionnaire – Female Lower Urinary Tract Symptoms (ICIQ‐FLUTS), measuring filling, voiding and incontinence. Data were compared with data on demographics and treatment‐related factors from the Danish Colorectal Cancer Group (DCCG) database.ResultsWe found that rectal cancer treatment significantly impaired urinary function compared with colon cancer treatment (filling score p = 0.003, voiding p < 0.0001, incontinence p = 0.0001). Radiotherapy was the single most influential risk factor for high filling (p = 0.0043), voiding (p < 0.0001) and incontinence (p < 0.0001) scores, whereas type of rectal resection was only significant in crude analysis. Urinary dysfunction was strongly associated with an impaired quality of life.ConclusionUrinary dysfunction is common after treatment for colorectal cancer, particularly if the treatment includes radiotherapy. All patients must be informed of the risk before cancer treatment, and functional outcome should be routinely assessed at follow‐up.
Development of a SARS‐CoV‐2 rapid antibody detection kit and study on dynamic changes in antibodies in infected patients
Authors: Wang Huihui , Li Xuemei , Li Tao , Wang Lianzi , Wang Li , Lin Jiawang , Zhang Shubing , Xu Yuanhong , Wei Wei 
Published: January 2021

AbstractIntroductionSevere acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has spread rapidly to 185 regions and countries around the world with more than 2.8 million confirmed infections and 203,044 deaths. Respiratory diseases caused by SARS‐CoV‐2 are serious threats to human health.ObjectivesTo develop a rapid detection kit for new coronavirus antibodies and use it to study the dynamic changes in antibodies in clinically confirmed SARS‐CoV‐2‐infected patients.MethodsThe SARS‐CoV‐2 IgM/IgG antibody test kit (colloidal gold method) was developed. Serum SARS‐CoV‐2 IgM and IgG antibodies were tested in SARS‐CoV‐2‐ and non‐SARS‐CoV‐2‐infected persons, respectively.Results and conclusionThe sensitivities of the SARS‐CoV‐2 IgM/IgG antibody test kit (colloidal gold method) were 50%, 70%, 92.5% and 97.5% after 1–3 days, 4–6 days, 7–9 days and >9 days of admission, respectively, and the specificities of the IgM, IgG and IgM + IgG antibodies were all 100%. Using the SARS‐CoV‐2 IgM/IgG antibody test kit (colloidal gold method), the positive rates of SARS‐CoV‐2 IgM and IgG antibodies increased from 50% to 92.5% after 1–3 days, 4–6 days and 7–9 days of admission, which showed an increasing trend. The titers of the SARS‐CoV‐2 IgM and IgG antibodies in the positive specimens increased with the length of admission.
Should CT be used for the diagnosis of RT‐PCR‐negative suspected COVID‐19 patients?
Authors: Rona Günay , Arifoğlu Meral , Voyvoda Nuray , Batırel Ayşe 
Published: January 2021

AbstractIntroductionThe diagnosis of patients with Coronavirus disease 2019 (COVID‐19) suspicion but negative reverse transcriptase‐polymerase chain reaction (RT‐PCR) test is challenging.ObjectiveWe aimed to investigate the diagnostic value of chest computed tomography (CT) in RT‐PCR‐negative patients with suspected COVID‐19.Materials and methodsThe study included patients who were admitted to our hospital with the suspicion of COVID‐19 between 1 April 2020 and 30 April 2020 and tested negative after RT‐PCR test, and underwent CT for further diagnosis. Initial CT findings were classified as typical, indeterminate, and atypical for COVID‐19, and negative for pneumonia. Incidental findings on CT were noted.ResultsOf the 338 patients with a mean age of 57 years (min 18 years–max 96 years), 168 (49.70%) were male and 170 (50.29%) were female. The most common symptoms were cough (58.87%), fever (40.82%), and dyspnea (39.34%). The CT findings were typical for COVID‐19 in 109 (32.24%) patients, indeterminate in 47 (13.90%) patients, and atypical in 77 (22.78%) patients. The CT findings of 105 (31.06%) patients were negative for pneumonia. Incidental lung nodules suspicious of malignancy were identified in seven patients. Seventy‐seven patients (22.78%) had extrapulmonary incidental findingsConclusionThe diagnostic value of CT in RT‐PCR‐negative patients with suspected COVID‐19 is not very high. Based on clinical, laboratory, and chest x‐ray findings, it may be more appropriate to refer patients to CT after the first triage, when necessary.
Association between p73 G4C14‐to‐A4T14 polymorphism and lung cancer risk: A systematic review and meta‐analysis
Authors: Du Fenghua , Wang Xiaojun , Qin Dandan , Zhu Rongjun , Kong Weibo , Kong Xiangzhou , Min Xuhong 
Published: January 2021

AbstractObjectiveThis study was conducted to evaluate the relationship between the p73 G4C14‐to‐A4T14 polymorphism (hereafter, G4C14‐to‐A4T14) and lung cancer risk.MethodsThe studies on the relationship between G4C14‐A4T14 and lung cancer risk published as of November 5, 2018, were comprehensively searched in PubMed, Embase, the Cochrane Library, the Chinese Wanfang database, China National Knowledge Infrastructure (CNKI), and China Biology Medicine (CBM). The last update was on May 24, 2019. Statistical analysis was performed using Stata 12.0.ResultsThe association between G4C14‐A4T14 and lung cancer risk was analyzed in nine studies. The findings indicate no association between G4C14‐to‐A4T14 and lung cancer risk (allele model: OR = 0.90, 95% CI: 0.73–1.11, I2 = 86.0%, P = .330; dominant model: OR = 0.93, 95% CI: 0.74–1.17, I2 = 82.6%, P = .551; recessive model: OR = 0.75, 95% CI: 0.50–1.13, I2 = 75.2%, P = .165; homozygote model: OR = 0.74, 95% CI: 0.47–1.17, I2 = 79.6%, P = .199; heterozygote model: OR = 0.98, 95% CI: 0.80–1.21, I2 = 75.8%, P = .879). The heterogeneity between subgroups by cancer types and genotyping method was significantly reduced. After the deletion of suspected duplicates, no association was found between G4C14‐to‐A4T14 and lung cancer susceptibility.ConclusionOur meta‐analysis confirms that G4C14‐to‐A4T14 is not significantly related to lung cancer risk.
Assessing risk of Lymantria dispar L. invasion management to monarch butterflies (Danaus plexippus)
Authors: Nunez‐Mir Gabriela C. , Walter Jonathan A. , Johnson Derek M. 
Published: January 2021

AbstractConflicting conservation goals that lead to management tradeoffs are not uncommon in conservation practice. In this study, we explore a potential conflict between the management of a destructive invasive insect pest, Lymantria dispar, and conservation of a widely declining iconic species, the monarch butterfly (Danaus plexippus). Specifically, we assess the risk of exposure of susceptible monarch larvae to aerial applications of Btk, a Lepidoptera‐specific larvicide used in L. dispar suppression and eradication. Our findings indicate minimal conflict between L. dispar management and monarch conservation, as spatial overlap between Btk aerial applications and monarch larvae was found to be marginal. Furthermore, the results of our study indicated specific actions management can take to further minimize potential conflict between these conservation goals. Our study could serve as a guide to other efforts to evaluate potential tradeoffs between the management of invasive species and the conservation of vulnerable species.
Habitat use as indicator of adaptive capacity to climate change
Authors: Teitelbaum Claire S. , Sirén Alexej P. K. , Coffel Ethan , Foster Jane R. , Frair Jacqueline L. , Hinton Joseph W. , Horton Radley M. , Kramer David W. , Lesk Corey , Raymond Colin , Wattles David W. , Zeller Katherine A. , Morelli Toni Lyn 
Published: January 2021

AbstractAimPopulations of cold‐adapted species at the trailing edges of geographic ranges are particularly vulnerable to the negative effects of climate change from the combination of exposure to warm temperatures and high sensitivity to heat. Many of these species are predicted to decline under future climate scenarios, but they could persist if they can adapt to warming climates either physiologically or behaviourally. We aim to understand local variation in contemporary habitat use and use this information to identify signs of adaptive capacity. We focus on moose (Alces alces), a charismatic species of conservation and public interest.LocationThe northeastern United States, along the trailing edge of the moose geographic range in North America.MethodsWe compiled data on occurrences and habitat use of moose from remote cameras and GPS collars across the northeastern United States. We use these data to build habitat suitability models at local and regional spatial scales and then to predict future habitat suitability under climate change. We also use fine‐scale GPS data to model relationships between habitat use and temperature on a daily temporal scale and to predict future habitat use.ResultsWe find that habitat suitability for moose will decline under a range of climate change scenarios. However, moose across the region differ in their use of climatic and habitat space, indicating that they could exhibit adaptive capacity. We also find evidence for behavioural responses to weather, where moose increase their use of forested wetland habitats in warmer places and/or times.Main conclusionsOur results suggest that there will be significant shifts in moose distribution due to climate change. However, if there is spatial variation in thermal tolerance, trailing‐edge populations could adapt to climate change. We highlight that prioritizing certain habitats for conservation (i.e., thermal refuges) could be crucial for this adaptation.