bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nivolumab for the salvage treatment of desperate germ cell tumor: A case report
Authors: Aksun MS , Ucgul E , Sahin TK , Guven DC , Aksoy S 
Published: December 2020

Introduction Testicular germ cell tumors (GCT) are the most common tumor in young men. Their distinctive feature is the exceptional response to platin based combination chemotherapy.Since the prognosis is poor in relapsed and refractory patients, the immune checkpoint inhibitors are candidate agents in these patients although clinical trials are mostly lacking. Herein, we describe a patient with a refractory nonseminomatous GCT using nivolumab as a last resort therapy and provided long term response without any significant toxicity. Case report A 41-year-old male presented with the complaint of flank pain eleven years ago. The patient underwent a retroperitoneal lymph node excision and pathology reported as the mixed germ cell tumor. There were no mass in the testicles and the patient was diagnosed with a primary retroperitoneal GCT. Since the disease has progressed under multiple lines of chemotherapy and autologous stem cell transplantation, treatment was started with nivolumab. Management and outcome The patient started to treatment with nivolumab 3 mg/kg two weekly as a last resort treatment. The nivolumab was continued and the patient's response to this treatment is ongoing and has been stable for 13 months. Discussion There are limited treatment options in platinum-refractory germ cell tumors. Recently, immune checkpoint inhibitors tried in this setting with some success in especially non-seminomatous GCTs. We see a good response and prolonged benefit with the use of nivolumab in our patient. Further research including prospective studies on the use of immune checkpoint inhibitors in platinum-resistant testicular cancer can further delineate the role of immunotherapy.
Evaluating the quality and safety of the BreastScreen remote radiology assessment model of service delivery in Australia
Authors: Lindsay Daniel , Bates Nicole , Callander Emily , Johnston Karen , Carlisle Karen , Smith Deb , Evans Rebecca , Larkins Sarah 
Published: December 2020

Introduction Breast cancer is the most commonly diagnosed cancer in Australian women. Given the diverse geography and populations within Australia, the ability to offer a telemedicine-supported breast screening and assessment service may increase access. The aim of this study was to assess clinical outcomes of a telemedicine-based remote radiology assessment service delivery model for detecting breast cancer in regional Australian women compared to the traditional radiologist onsite model. Methods This study was a pre–post intervention study using de-identified administrative data. Data were collected from seven sites across three health jurisdictions within Australia. There were a total of 21,117 assessment visits, with 10,508 (49.8%) pre- and 10,609 (50.2%) post-remote model implementation. Of the 10,609 post-remote model visits, 3,904 (36.8%) were under the remote model. The main outcome was cancer detection, split into any cancer, any invasive cancer or any small invasive cancer. Timeliness of assessment was also examined. Results After adjusting for multiple factors, there were no statistically significant differences in cancer detection rates between the remote and onsite models (adjusted odds ratio (AOR) = 1.02, 95% CI 0.86–1.19, n.s.). Implementing the remote assessment model had statistically significant positive effects on the timeliness of assessment (AOR = 0.68, 95% CI 0.59–0.77, p < 0.001). Discussion This study found the remote model delivers safe and high-quality assessment services, with equivalent rates of cancer detection and improved timeliness of assessment when compared to the traditional onsite model. Careful monitoring and ongoing evaluation of any health-service model is important for ongoing safety, efficiency and acceptability.
Social work, emotion management and the transformation of the welfare state
Authors: Turtiainen Jussi , Anttila Erkko , Väänänen Ari 
Published: December 2020

Summary Drawing from the sociological and organizational scholarship of emotion management in human service work, our historical analysis elaborates on how external pressures and efficiency requirements jeopardize employees’ ability to carry out emotional labour in the public sector. Building on the Finnish social workers’ accounts published in a professional trade paper in 1975–2009, the article provides an insight into the emotional challenges and dissonances of interactive work. Findings The article suggests that social workers’ emotional job requirements are deeply embedded in and influenced by the broader social context and changes in the welfare state. The article indicates how workers’ emotion management underwent changes and readjustments from the heyday of the expansive welfare state of the mid-1970s, through the severe economic recession of the 1990s, and was bound by the ideological reform of the Finnish welfare policy in the 1990s and 2000s. Applications Historical prospect to emotion management shows social workers, social work students and the academic community how employees’ emotion management has been gradually recognized as a crucial element of relational client work over the decades, but also how workers’ emotional job requirements and demeanours are intertwined with broader societal changes. Second, emotion management research provides a solid framework to elaborate emotional and ethical dissonances which are embedded in social work more profoundly.
Variant in NHLRC2 leads to increased hnRNP C2 in developing neurons and the hippocampus of a mouse model of FINCA disease
Authors: Hiltunen Anniina E. , Kangas Salla M. , Ohlmeier Steffen , Pietilä Ilkka , Hiltunen Jori , Tanila Heikki , McKerlie Colin , Govindan Subashika , Tuominen Hannu , Kaarteenaho Riitta , Hallman Mikko , Uusimaa Johanna , Hinttala Reetta 
Published: December 2020

Abstract
Background
FINCA disease is a pediatric cerebropulmonary disease caused by variants in the NHL repeat-containing 2 (NHLRC2) gene. Neurological symptoms are among the first manifestations of FINCA disease, but the consequences of NHLRC2 deficiency in the central nervous system are currently unexplored.

Methods
The orthologous mouse gene is essential for development, and its complete loss leads to early embryonic lethality. In the current study, we used CRISPR/Cas9 to generate an Nhlrc2 knockin (KI) mouse line, harboring the FINCA patient missense mutation (c.442G > T, p.Asp148Tyr). A FINCA mouse model, resembling the compound heterozygote genotype of FINCA patients, was obtained by crossing the KI and Nhlrc2 knockout mouse lines. To reveal NHLRC2-interacting proteins in developing neurons, we compared cortical neuronal precursor cells of E13.5 FINCA and wild-type mouse embryos by two-dimensional difference gel electrophoresis.

Results
Despite the significant decrease in NHLRC2, the mice did not develop severe early onset multiorgan disease in either sex. We discovered 19 altered proteins in FINCA neuronal precursor cells; several of which are involved in vesicular transport pathways and actin dynamics which have been previously reported in other cell types including human to have an association with dysfunctional NHLRC2. Interestingly, isoform C2 of hnRNP C1/C2 was significantly increased in both developing neurons and the hippocampus of adult female FINCA mice, connecting NHLRC2 dysfunction with accumulation of RNA binding protein.

Conclusions
We describe here the first NHLRC2-deficient mouse model to overcome embryonic lethality, enabling further studies on predisposing and causative mechanisms behind FINCA disease. Our novel findings suggest that disrupted RNA metabolism may contribute to the neurodegeneration observed in FINCA patients.
High-expression of ROCK1 modulates the apoptosis of lens epithelial cells in age-related cataracts by targeting p53 gene
Authors: Hu Shanshan , Su Dongmei , Sun Lei , Wang Zhongying , Guan Lina , Liu Shanhe , Zhao Baowen , Liu Yong , Shi Cuige , Yu Jianbo , Ma Xu 
Published: December 2020

Abstract
Background
Age-related cataract (ARC) is a serious visual impairment disease, and its pathogenesis is unclear. This article aims to investigate the role of ROCK1 in the apoptosis of lens epithelial cells (LECs) in age-related cataracts.

Methods
We collect anterior capsule samples from normal people, patients with age-related cataracts, young mice and naturally aging cataract mice. The oxidative stress-induced apoptosis model was constructed by cultivating HLE-B3 cells with H2O2. MTT, Hoechst 33342, and TUNEL assay were performed to explore proliferation and apoptosis. HE assay was used to observe cell morphology. The gene and protein expression were assessed by quantitative real-time PCR, western blot, immunofluorescence, and immunohistochemical staining.

Result
The results from the clinic and mice experiments showed that the numbers of lens epithelial cells from cataract individuals were less than the control individuals. In vitro, the apoptotic cells were increased in lens epithelial cells under H2O2 treatment. The ROCK1 protein level increased in the lens epithelial cells from age-related cataract patients and the old mice, respectively. Meanwhile, the up-regulation of the ROCK1 gene was associated with H2O2-induced HLE-B3 cells apoptosis. MTT and apoptosis assay showed ROCK1 was necessary in mediating H2O2-induced lens epithelial cells apoptosis through ROCK1 over-expression and knockdown experiment, respectively. Further investigation showed that p53 protein levels had been increased during ROCK1-mediated apoptosis in response to H2O2. Besides, ROCK1 phosphorylated p53 at ser15 to up-regulate its protein level.

Conclusions
This study established the novel association of ROCK1/p53 signaling with lens epithelial cells apoptosis and age-related cataract genesis.
Identification of an RNA binding protein-related gene signature in hepatocellular carcinoma patients
Authors: Wang Li , Zhou Na , Qu Jialin , Jiang Man , Zhang Xiaochun 
Published: December 2020

Abstract
Background
Hepatocellular carcinoma (HCC) is a common malignant primary cancer with high mortality. Previous studies have demonstrated that RNA binding proteins (RBPs) are involved in the biological processes of cancers, including hepatocellular cancer.

Methods
In this study, we aimed to identify the clinical value of RNA-binding proteins for hepatocellular carcinoma. We obtained gene expression and clinical data of hepatocellular carcinoma patients from the TCGA and ICGC databases. The prognostic value of RBP-related genes in patients with hepatocellular carcinoma and their function were studied by comprehensive bioinformatics analyses. The gene signature of SMG5, EZH2, FBLL1, ZNF239, and IGF2BP3 was generated by univariate and multivariate Cox regression and LASSO regression analyses. We built and verified a prognostic nomogram based on RBP-related genes. The gene signature was validated by the ICGC database. The expression of RBP-related genes was validated by the Oncomine database, the Human Protein Atlas and Kaplan–Meier plotter.

Result
Most RBP-related genes were significantly different in cancer and normal tissues. The survival of patients in the different groups was significantly different. The gene signature showed good performance for predicting the survival of HCC patients by having a better area under the receiver operating characteristic curve than other clinicopathological parameters.

Conclusion
Gene signatures based on RNA-binding proteins can be independent risk factors for hepatocellular carcinoma patients.
Escape from X chromosome inactivation and female bias of autoimmune diseases
Authors: Mousavi Mohammad Javad , Mahmoudi Mahdi , Ghotloo Somayeh 
Published: December 2020

AbstractGenerally, autoimmune diseases are more prevalent in females than males. Various predisposing factors, including female sex hormones, X chromosome genes, and the microbiome have been implicated in the female bias of autoimmune diseases. During embryogenesis, one of the X chromosomes in the females is transcriptionally inactivated, in a process called X chromosome inactivation (XCI). This equalizes the impact of two X chromosomes in the females. However, some genes escape from XCI, providing a basis for the dual expression dosage of the given gene in the females. In the present review, the contribution of the escape genes to the female bias of autoimmune diseases will be discussed.
A scoping review of worldwide studies evaluating the effects of prehospital time on trauma outcomes
Authors: Bedard Alexander F. , Mata Lina V. , Dymond Chelsea , Moreira Fabio , Dixon Julia , Schauer Steven G. , Ginde Adit A. , Bebarta Vikhyat , Moore Ernest E. , Mould-Millman Nee-Kofi 
Published: December 2020

AbstractBackgroundAnnually, over 1 billion people sustain traumatic injuries, resulting in over 900,000 deaths in Africa and 6 million deaths globally. Timely response, intervention, and transportation in the prehospital setting reduce morbidity and mortality of trauma victims. Our objective was to describe the existing literature evaluating trauma morbidity and mortality outcomes as a function of prehospital care time to identify gaps in literature and inform future investigation.Main bodyWe performed a scoping review of published literature in MEDLINE. Results were limited to English language publications from 2009 to 2020. Included articles reported trauma outcomes and prehospital time. We excluded case reports, reviews, systematic reviews, meta-analyses, comments, editorials, letters, and conference proceedings. In total, 808 articles were identified for title and abstract review. Of those, 96 articles met all inclusion criteria and were fully reviewed. Higher quality studies used data derived from trauma registries. There was a paucity of literature from studies in low- and middle-income countries (LMIC), with only 3 (3%) of articles explicitly including African populations. Mortality was an outcome measure in 93% of articles, predominantly defined as “in-hospital mortality” as opposed to mortality within a specified time frame. Prehospital time was most commonly assessed as crude time from EMS dispatch to arrival at a tertiary trauma center. Few studies evaluated physiologic morbidity outcomes such as multi-organ failure.ConclusionThe existing literature disproportionately represents high-income settings and most commonly assessed in-hospital mortality as a function of crude prehospital time. Future studies should focus on how specific prehospital intervals impact morbidity outcomes (e.g., organ failure) and mortality at earlier time points (e.g., 3 or 7 days) to better reflect the effect of early prehospital resuscitation and transport. Trauma registries may be a tool to facilitate such research and may promote higher quality investigations in Africa and LMICs.
Cerebrospinal fluid findings and hypernatremia in COVID-19 patients with altered mental status
Authors: Toklu Hale , Ganti Latha , Crimi Ettore , Cintron Cristobal , Hagan Joshua , Serrano Enrique 
Published: December 2020

Abstract
Background
The objective of the study was to assess the cerebrospinal fluid (CSF) findings in COVID-19 patients.

Aims
This was an observational retrospective cohort from electronic medical records of hospitalized patients (n = 2655) with confirmed COVID-19 between February 15, 2020, and April 15, 2020, in 182 hospitals from a large health system in the USA. The review of data yielded to a total of 79 patients in 20 hospitals who had CSF analysis.

Methods
Outcomes during hospitalization, including hospital length of stay, disease severity, ventilator time, and in-hospital death were recorded. Independent variables collected included patient demographics, diagnoses, laboratory values, and procedures.

Results
A total of 79 patients underwent CSF analysis. Of these, antigen testing was performed in 73 patients. Ten patients had CSF analysis for general markers such as total protein, cell count, glucose, clarity, and color. Seven of the 10 cases (70%) had normal total cell count and normal white blood cell count in CSF. Sixty-three percent (5/8) had elevated total protein. Two patients had normal levels of lactate dehydrogenase (LDH) and 1 patient had significantly elevated (fourfold) neuron-specific enolase (NSE) level in CSF.

Conclusion
Unlike bacterial infections, viral infections are less likely to cause remarkable changes in CSF glucose, cell count, or protein. Our observations showed no pleocytosis, but mild increase in protein in the CSF of the COVID-19 patients. The fourfold elevation of NSE may have diagnostic/prognostic value as a biomarker in CSF for COVID-19 patients who have altered mental status.

Graphical abstract
Linear space string correction algorithm using the Damerau-Levenshtein distance
Authors: Zhao Chunchun , Sahni Sartaj 
Published: December 2020

Abstract
Background
The Damerau-Levenshtein (DL) distance metric has been widely used in the biological science. It tries to identify the similar region of DNA,RNA and protein sequences by transforming one sequence to the another using the substitution, insertion, deletion and transposition operations. Lowrance and Wagner have developed an O(mn) time O(mn) space algorithm to find the minimum cost edit sequence between strings of length m and n, respectively. In our previous research, we have developed algorithms that run in O(mn) time using only O(s∗min{m,n}+m+n) space, where s is the size of the alphabet comprising the strings, to compute the DL distance as well as the corresponding edit sequence. These are so far the fastest and most space efficient algorithms. In this paper, we focus on the development of algorithms whose asymptotic space complexity is linear.

Results
We develop linear space algorithms to compute the Damerau-Levenshtein (DL) distance between two strings and determine the optimal trace (corresponding edit operations.)Extensive experiments conducted on three computational platforms–Xeon E5 2603, I7-x980 and Xeon E5 2695–show that, our algorithms, in addition to using less space, are much faster than earlier algorithms.

Conclusion
Besides using less space than the previously known algorithms,significant run-time improvement was seen for our new algorithms on all three of our experimental platforms. On all platforms, our linear-space cache-efficient algorithms reduced run time by as much as 56.4% and 57.4% in respect to compute the DL distance and an optimal edit sequences compared to previous algorithms. Our multi-core algorithms reduced the run time by up to 59.3% compared to the best previously known multi-core algorithms.
The evolution of the huntingtin-associated protein 40 (HAP40) in conjunction with huntingtin
Authors: Seefelder Manuel , Alva Vikram , Huang Bin , Engler Tatjana , Baumeister Wolfgang , Guo Qiang , Fernández-Busnadiego Rubén , Lupas Andrei N. , Kochanek Stefan 
Published: December 2020

AbstractBackgroundThe huntingtin-associated protein 40 (HAP40) abundantly interacts with huntingtin (HTT), the protein that is altered in Huntington’s disease (HD). Therefore, we analysed the evolution of HAP40 and its interaction with HTT.ResultsWe found that in amniotes HAP40 is encoded by a single-exon gene, whereas in all other organisms it is expressed from multi-exon genes. HAP40 co-occurs with HTT in unikonts, including filastereans such asCapsaspora owczarzakiand the amoebozoanDictyostelium discoideum,but both proteins are absent from fungi.Outside unikonts, a few species, such as the free-living amoeboflagellateNaegleria gruberi, contain putative HTT and HAP40 orthologs.Biochemically we show that the interaction between HTT and HAP40 extends to fish, and bioinformatic analyses provide evidence for evolutionary conservation of this interaction. The closest homologue of HAP40 in current protein databases is the family of soluble N-ethylmaleimide-sensitive factor attachment proteins (SNAPs).ConclusionOur results indicate that the transition from a multi-exon to a single-exon gene appears to have taken place by retroposition during the divergence of amphibians and amniotes, followed by the loss of the parental multi-exon gene. Furthermore, it appears that the two proteins probably originated at the root of eukaryotes. Conservation of the interaction between HAP40 and HTT and their likely coevolution strongly indicate functional importance of this interaction.
Apneic laryngeal oxygenation during elective fiberoptic intubation – a technical simulation
Authors: Schroeder Daniel C. , Wetsch Wolfgang A. , Finke Simon-Richard , Dusse Fabian , Böttiger Bernd W. , Herff Holger 
Published: December 2020

Abstract
Background
Sedation during elective fiberoptic intubation for difficult airway can cause respiratory depression, apnea and periods of desaturation. During apneic episodes, hypoxemia can be prevented by insufflation of oxygen in the deep laryngeal space. The aim of this study was to evaluate an oropharyngeal oxygenation device (OOD) designed for deep laryngeal insufflation during fiberoptic intubation.

Methods
The OOD is split in the front to form a path for the bronchoscope. An external lumen delivers oxygen in the deep laryngeal space. In this experimental study, air application (as control group), oxygen application via nasal prongs, oxygen application via the OOD, and oxygen application via the working channel of a bronchoscope were compared in a technical simulation. In a preoxygenated test lung of a manikin, decrease of the oxygen saturation was measured over 20 min for each method.

Results
Oxygen saturation in the test lung dropped from 97 ± 1% (baseline in all groups) to 58 ± 3% in the control-group (p < 0.001 compared to all other groups) and to 78 ± 1% in the nasal prong group (p < 0.001 compared to all other groups). Oxygen saturation remained at 95 ± 2% in both the OOD group and the bronchoscopy group (p = 0.451 between those two groups).

Conclusion
Simulating apneic laryngeal oxygenation in a preoxygenated manikin, both oxygen insufflation via the OOD and the bronchoscope kept oxygen saturation in the test lung at 95% over 20 min. Both methods significantly were more effective than oxygen insufflation via nasal prongs.
Endoscopic ultrasound with fine needle aspiration is useful in pancreatic cysts smaller than 3 cm
Authors: Faias Sandra , Cravo Marília , Pereira da Silva João , Chaves Paula , Dias Pereira A. 
Published: December 2020

Abstract
Background
In current guidelines, endoscopic ultrasound with fine-needle aspiration (EUS-FNA) is recommended in pancreatic cystic lesions (PCLs) with worrisome features (size ≥ 3 cm, mural nodule, or Wirsung dilation).

Objective
To evaluate the diagnostic ability and assess the accuracy of EUS-FNA in PCLs smaller than 3 cm.

Methods
Retrospective study of PCLs < 3 cm (2007–2016) undergoing EUS-FNA. Clinical, EUS and pancreatic cystic fluid (PCF) data were prospectively registered. Performance of EUS-FNA with PCF analysis for the detection of malignancy and accuracy in surgical cohort were analyzed.

Results
We evaluated 115 patients with PCLs < 3 cm who underwent EUS-FNA. 19 patients underwent surgery, 7 had malignant, 8 pre-malignant, and the remaining 4 benign lesions. Mass/mural nodule was present in 27% of the cysts, CEA level was higher than 192 ng/mL in 39.4% of patients, and only 35% of cytologic samples were informative. Nevertheless, additional FNA for PCF analysis improved the diagnostic performance of EUS imaging—AUC = 0.80 versus AUC = 60.

Conclusion
EUS-FNA has good accuracy in PCLs < 3 cm. It confirmed malignancy even in lesions without worrisome features (nodule/mass), with two in every five resections showing high-risk/malignant lesions. EUS-FNA was also useful to diagnose benign cysts, possibly allowing surveillance to be stopped in one in every five patients.