bluuebunny/crossref_metadata_2025_split huggingface dataset:
The diagnostic challenge of coexistent sarcoidosis and thyroid cancer – a retrospective study
Authors: Wenter Vera , Albert Nathalie L. , Ahmaddy Freba , Unterrainer Marcus , Hornung Julia , Ilhan Harun , Bartenstein Peter , Spitzweg Christine , Kneidinger Nikolaus , Todica Andrei 
Published: February 2021

AbstractBackgroundSarcoid lesions may mimic metastatic disease or recurrence in thyroid cancer (TC) patients as both diseases may affect the lungs and lymph nodes. We present the first study to systematically evaluate the clinical course of patients with (TC) after adjuvant radioactive iodine therapy (RIT) and concomitant sarcoidosis of the lung or the lymph nodes.MethodsWe screened 3285 patients and retrospectively identified 16 patients with TC (11 papillary thyroid cancer (PTC), 3 follicular thyroid cancer (FTC), 1 oncocytic PTC, 1 oncocytic FTC) and coexisting sarcoidosis of the lung and/or the lymph nodes treated at our institute. All patients had undergone thyroidectomy and initial adjuvant RIT. Challenges in diagnosing and the management of these patients were evaluated during long term follow-up (median 4.9 years (0.8–15.0 years)).ResultsMedian age at first diagnosis of TC was 50.1 years (33.0–71.5 years) and of sarcoidosis 39.4 years (18.0–63.9 years). During follow-up, physicians were able to differentiate between SA and persistent or recurrent TC in 10 of 16 patients (63%). Diagnosis was complicated by initial negative thyroglobulin (Tg), positive Tg antibodies and non-specific imaging findings. Histopathology can reliably distinguish between SA and TC in patients with one suspicious lesion.ConclusionPhysicians should be aware of the rare coexistence of sarcoidosis and TC. Lymphadenopathy and pulmonary lesions could be metastases, sarcoidosis or even a mix of both. Therefore, this rare patient group should receive a thorough work up including histopathological clarification and, if necessary, separately for each lesion.
False negative rate at 18F-FDG PET/CT in para-aortic lymphnode involvement in patients with locally advanced cervical cancer: impact of PET technology
Authors: Gouy Sebastien , Seebacher Veronika , Chargari Cyrus , Terroir Marie , Grimaldi Serena , Ilenko Anna , Maulard Amandine , Genestie Catherine , Leary Alexandra , Pautier Patricia , Morice Philippe , Deandreis Désirée 
Published: February 2021

Abstract
Background
The identification of factors responsible for false negative (FN) rate at 18F- Fluorodeoxyglucose (FDG) Positron Emission Tomography /Computed Tomography (PET/CT) in para-aortic (PA) lymph nodes in the presurgical staging of patients with locally advanced cervical cancer (LACC) is challenging. The aim of this study was to evaluate the impact of PET/CT technology.

Methods
A total of 240 consecutive patients with LACC (International Federation of Gynecology and Obstetrics, FIGO, stage IB2-IVA) and negative Magnetic Resonance Imaging (MRI) and/or Computed Tomography (CT) and negative 18F-FDG PET/CT in the PA region, undergoing laparoscopic PA lymphadenectomy before chemoradiotherapy were included. The FN rate in patients studied with Time of flight (TOF) PET/CT (TOF PET) or non-Time of flight PET/CT (no-TOF PET) technology was retrospectively compared.

Results
Patients presented with FIGO stage IB (n = 78), stage IIA-B (n = 134), stage III (n = 18) and stage IVa (n = 10), squamous cell carcinoma (n = 191) and adenocarcinoma (n = 49). 141/240 patients were evaluated with no-TOF PET/CT and 99/240 with TOF PET/CT. Twenty-two patients (9%) had PA nodal involvement at histological analysis and considered PET/CT FN findings. The FN rate was 8.5% for no-TOF PET and 10% for TOF PET subgroup respectively (p = 0.98). Ninety patients (38%) presented with pelvic node uptakes at PET/CT. The FN rate in the PA region was 18% (16/90) and 4% (6/150) in patients with and without pelvic node involvement at PET/CT respectively (19 vs 3% for no-TOF PET and 17 vs 5% for TOF PET subgroup).

Conclusions
In LACC, FN rate in PA lymph nodes detection is a clinical issue even for modern PET/CT, especially in patients with pelvic uptake. Surgical lymphadenectomy should be performed in case of negative PET/CT at PA level in these patients, while it could be discussed in the absence of pelvic uptake.
Diverse mechanisms activate the PI 3-kinase/mTOR pathway in melanomas: implications for the use of PI 3-kinase inhibitors to overcome resistance to inhibitors of BRAF and MEK
Authors: Tran Khanh B. , Kolekar Sharada , Jabed Anower , Jaynes Patrick , Shih Jen-Hsing , Wang Qian , Flanagan Jack U. , Rewcastle Gordon W. , Baguley Bruce C. , Shepherd Peter R. 
Published: February 2021

Abstract
Background
The PI 3-kinase (PI3K) pathway has been implicated as a target for melanoma therapy.

Methods
Given the high degree of genetic heterogeneity in melanoma, we sought to understand the breadth of variation in PI3K signalling in the large NZM panel of early passage cell lines developed from metastatic melanomas.

Results
We find the vast majority of lines show upregulation of this pathway, and this upregulation is achieved by a wide range of mechanisms. Expression of all class-IA PI3K isoforms was readily detected in these cell lines. A range of genetic changes in different components of the PI3K pathway was seen in different lines. Coding variants or amplification were identified in the PIK3CA gene, and amplification of the PK3CG gene was common. Deletions in the PIK3R1 and PIK3R2 regulatory subunits were also relatively common. Notably, no genetic variants were seen in the PIK3CD gene despite p110δ being expressed in many of the lines. Genetic variants were detected in a number of genes that encode phosphatases regulating the PI3K signalling, with reductions in copy number common in PTEN, INPP4B, INPP5J, PHLLP1 and PHLLP2 genes. While the pan-PI3K inhibitor ZSTK474 attenuated cell growth in all the lines tested, isoform-selective inhibition of p110α and p110δ inhibited cell growth in only a subset of the lines and the inhibition was only partial. This suggests that functional redundancy exists between PI3K isoforms. Furthermore, while ZSTK474 was initially effective in melanoma cells with induced resistance to vemurafenib, a subset of these cell lines concurrently developed partial resistance to PI3K inhibition. Importantly, mTOR-selective or mTOR/PI3K dual inhibitors effectively inhibited cell growth in all the lines, including those already resistant to BRAF inhibitors and ZSTK474.

Conclusions
Overall, this indicates a high degree of diversity in the way the PI3K pathway is activated in different melanoma cell lines and that mTOR is the most effective point for targeting the growth via the PI3K pathway across all of these cell lines.
LncRNA MT1JP plays a protective role in intrahepatic cholangiocarcinoma by regulating miR-18a-5p/FBP1 axis
Authors: Zhao Wei , Zhao Jing , Guo Xiao , Feng Yujie , Zhang Bingyuan , Tian Lantian 
Published: February 2021

Abstract
Background
Cholangiocarcinoma is a common malignant tumor of digestive system. LncRNA metallothionein 1 J, pseudogene (MT1JP) has been reported to play tumor-suppressing roles in multiple cancers. However, its effect on cholangiocarcinoma has not been evaluated.

Methods
The expression of MT1JP in intrahepatic cholangiocarcinoma specimens and paired para-carcinoma tissues were detected by real-time PCR. The overexpression plasmid and siRNA of MT1JP were transfected into intrahepatic cholangiocarcinoma cells to change the expression levels of MT1JP. CCK-8, flow cytometry and transwell assays were performed to measure proliferation, cell cycle transition, apoptosis, migration and invasion. Dual-luciferase reporter assay, real-time PCR and western blot were carried out to screen the miRNA bound by MT1JP. In addition, xenograft experiment was used to determine the tumorigenesis of cholangiocarcinoma cells in nude mice.

Results
MT1JP was downregulated in intrahepatic cholangiocarcinoma specimens, and its expression was related with TNM stage and lymph node metastasis. Overexpression of MT1JP inhibited proliferation, cell cycle transition, migration and invasion, and induced apoptosis in intrahepatic cholangiocarcinoma cells. The knockdown of MT1JP led to opposite results. MT1JP bound to miR-18a-5p to facilitate the expression of fructose-1,6-bisphosphatase 1 (FBP1). MiR-18a-5p was increased in intrahepatic cholangiocarcinoma samples, and its expression was negatively correlated with that of MT1JP. In addition, MT1JP also suppressed tumorigenesis in nude mice.

Conclusions
MT1JP alleviated proliferation, migration and invasion, and induced apoptosis in cholangiocarcinoma cells by regulating miR-18a-5p/FBP1 axis. These findings may provide novel insights for clinical diagnosis and treatment of cholangiocarcinoma.
A prognosis-related molecular subtype for early-stage non-small lung cell carcinoma by multi-omics integration analysis
Authors: Yang Kai , Wu Ying 
Published: February 2021

AbstractBackgroundEarly-stage non-small cell lung carcinoma (NSCLC) accounts for more than 80% of lung cancer, which is a kind of cancer with high heterogeneity, so the genetic heterogeneity and molecular subtype should be explored.MethodsPartitioning Around Medoid algorithm was used to acquire the molecular subtype for early-stage NSCLC based on prognosis-related mRNAs and methylation sites. Random forest (RF) and support vector machine (SVM) were used to build prediction models for subtypes.ResultsSix prognosis-related subtypes for early-stage NSCLC, including 4 subtypes for lung squamous cell carcinoma (LUSC) and 2 subtypes for lung adenocarcinoma (LUAD), were identified. There were highly expressed and hypermethylated gene regions for LUSC-C1 and LUAD-C2, highly expressed region for LUAD-C1, and hypermethylated regions for LUSC-C3 and LUSC-C4. Molecular subtypes for LUSC were mainly determined by DNA methylation (14 mRNAs and 362 methylation sites). Molecular subtypes for LUAD were determined by both mRNA and DNA methylation information (143 mRNAs and 458 methylation sites). Ten methylation sites were selected as biomarkers for prediction of LUSC-C1 and LUSC-C3, respectively. Nine genes and 1 methylation site were selected as biomarkers for LUAD subtype prediction. These subtypes can be predicted by the selected biomarkers with RF and SVM models.ConclusionsIn conclusion, we proposed a prognosis-related molecular subtype for early-stage NSCLC, which can provide important information for personalized therapy of patients.
A novel scoring system integrating molecular abnormalities with IPSS-R can improve the risk stratification in patients with MDS
Authors: Gu Siyu , Xia Jingya , Tian Yulu , Zi Jie , Ge Zheng 
Published: February 2021

Abstract
Background
The treatment strategies for Myelodysplastic Syndromes (MDS) are usually based on the risk stratification system. However, few risk signatures which integrate the revised international prognostic scoring system (IPSS-R) with gene mutations can be easily applied in the real world.

Methods
The training cohort of 63 MDS patients was conducted at Zhongda Hospital of Southeast University from January 2013 to April 2020. The validation cohort of 141 MDS patients was obtained from GSE129828. The mutation scoring system was based on the number of mutations and a unique favorable prognostic factor, which is SF3B1 mutation. Univariate Cox, multivariate Cox, and LASSO regression analyses were used to determine the significant factors that influenced the overall survival. The receiver operating characteristic curve (ROC) was used to evaluate the efficiency of the prognostic model.

Results
A novel risk scoring system we named “mutation combined with revised international prognostic scoring system (MIPSS-R)” was developed based on the results derived from multivariate analysis which assigned points to the IPSS-R and the mutation scores according to their relative statistical weight. Based on the quintile of the new scores, patients were divided into five risk levels. The Kaplan-Meier curves showed the superiority of MIPSS-R in separating patients from different groups, comparing with IPSS-R both in the training cohort (p = 1.71e-08 vs. p = 1.363e-04) and validation cohort (p = 1.788e-04 vs. p = 2.757e-03). The area under the ROC of MIPSS-R was 0.79 in the training cohort and 0.62 in the validation cohort. The retrospective analysis of our house patients showed that the risk levels of 57.41% of patients would adjust according to MIPSS-R. After changing risk levels, 38.71% of patients would benefit from treatment strategies that MIPSS-R recommends.

Conclusion
A mutation scoring system was conducted based on the number of mutations and a unique favorable prognostic factor. MIPSS-R, the novel integral risk stratification system was developed by integrating IPSS-R and the mutation scores, which is more effective on prognosis and treatment guidance for MDS patients.
Cisplatin plus paclitaxel chemotherapy with or without bevacizumab in postmenopausal women with previously untreated advanced cervical cancer: a retrospective study
Authors: Chu Guanghua , Liu Xiangzhen , Yu Weiguang , Chen Meiji , Dong Lingyun 
Published: February 2021

Abstract
Background
The aim of this study was to assess the survival outcomes of cisplatin-paclitaxel chemotherapy plus bevacizumab (CPB) versus cisplatin-paclitaxel chemotherapy alone (CPA) in postmenopausal women with previously untreated advanced cervical cancer (CC).

Methods
Consecutive postmenopausal women who experienced CPB or CPA were identified retrospectively from our medical centre during 2015–2019. Follow-up visits occurred 1 and 3 months after starting CPB or CPA. Afterwards, this assessment was conducted every 3 months for 1 year and then yearly thereafter. The primary endpoints were overall survival (OS) and progression-free survival (PFS); secondary endpoints were the frequency and severity of adverse events (AEs).

Results
Two hundred forty-six postmenopausal women were included (CPB, n = 124; CPA, n = 122). The median follow-up for the entire cohort was 24 months (range, 2–32). At the final follow-up, a significant difference was detected in terms of median OS (16.4 months [95% CI, 15.3–17.1] for CPB vs. 12.3 months [95% CI, 10.2–13.5] for CPA; hazard ratio (HR) 0.69, 95% CI, 0.49–0.99; p = 0.001), and the median PFS was longer in the CPB group than in the CPA group (9.2 months [95% CI, 8.3–10.7] vs. 7.9 months (95% CI, 6.1–8.6) (HR 0.62, 95% CI, 0.47–0.82; p < 0.001). There were significant differences in the number of AEs between the groups (hypertension grade ≥ 2 [p < 0.001], neutropenia grade ≥ 4 [p < 0.001], and thrombosis/embolism grade ≥ 3 [p = 0.030]).

Conclusions
Among postmenopausal women with previously untreated advanced CC, those who received CPB experienced superior survival benefits compared to those who received CPA. The safety profile for CPB was controllable despite the long duration of CPB use.
A randomized trial evaluating efficacy of overminus lenses combined with prism in the children with intermittent exotropia
Authors: Feng Yuelan , Jiang Jingjing , Bai Xueqing , Li Hui , Li Ningdong 
Published: February 2021

Abstract
Background
To evaluate the efficacy of overminus lenses combined with prism spectacles in children of 3 to 6 years of age with intermittent exotropia (IXT).

Methods
Sixty patients with IXT were randomly assigned to the treatment and observation groups. Each group included 30 IXT children aged 3 to 6 years. The treatment group was prescribed overminus lenses of − 2.50 D incorporated with the 2 PD base-in prisms on each side. Ocular alignment, the status of binocular vision, as well as the refraction changes were carried out and followed at 1, 3, 6, and 12 months. A revised form of the Newcastle Control Score (NCS) was used to evaluate the patients’ ability to control their IXT.

Results
After 12 months, the mean refractive error was 1.42 ± 1.25 D, and 1.43 ± 1.12 D for the observation and the treatment group, respectively (95% CI: − 0.61 to 0.62)); the mean exotropia control score was 5.72 ± 1.28 and 1.75 ± 1.18 in the observation and the treatment group, respectively (95% CI: − 4.63 to − 3.33); the mean near stereoacuity was 2.16 ± 0.42 log arcsec and 1.91 ± 0.26 log arcsec in the observation and the treatment group, respectively (95% CI: − 0.44 to − 0.06).

Conclusions
In our randomized clinical trial, overminus spectacles with prism significantly improved the control of IXT and stereopsis, by reducing the angle of strabismus in children with IXT. This treatment does not appear to cause myopia, at least in the manner used this series. A further randomized trial is warranted to assess the effect of overminus spectacles with prism after the treatment has been discontinued.

Trial registration
This study adheres to CONSORT 2010 guidelines. Chinese Clinical Trial Registry, ChiCTR1900025243. Registered 17 August 2019.
Concurrent and predictive validity of the infant motor profile in infants at risk of neurodevelopmental disorders
Authors:   the Clinical CareToy-R Consortium, Rizzi Riccardo , Menici Valentina , Cioni Maria Luce , Cecchi Alessandra , Barzacchi Veronica , Beani Elena , Giampietri Matteo , Cioni Giovanni , Sgandurra Giuseppina 
Published: February 2021

AbstractBackgroundPreterm infants and infants with perinatal brain injury show a higher incidence of neurodevelopmental disorders (NDD). The Infant Motor Profile (IMP) is a clinical assessment which evaluates the complexity of early motor behaviour. More data are needed to confirm its predictive ability and concurrent validity with other common and valid assessments such as the Alberta Infant Motor Scale (AIMS) and Prechtl’s General Movement Assessment (GMA). The present study aims to evaluate the concurrent validity of the IMP with the AIMS, to assess its association with the GMA, to evaluate how the IMP reflects the severity of the brain injury and to compare the ability of the IMP and the AIMS to predict an abnormal outcome in 5-month-old infants at risk of NDD.Methods86 infants at risk of NDD were retrospectively recruited among the participants of two clinical trials. Preterm infants with or without perinatal brain injury and term infants with brain injury were assessed at 3 months corrected age (CA) using the GMA and at 5 months CA using the IMP and the AIMS. The neurodevelopmental outcome was established at 18 months.ResultsResults confirm a solid concurrent validity between the IMP Total Score and the AIMS (Spearman’s ρ 0.76;p < .001) and a significant association between IMP Total Score and the GMA. Unlike the AIMS, the IMP Total score accurately reflects the severity of neonatal brain injury (p < .001) and proves to be the strongest predictor of NDD (p < .001). The comparison of ﻿areas under receiver operating characteristic curves (AUC) confirms that the IMP Total score has the highest diagnostic accuracy at 5 months (AUC 0.92). For an optimal IMP Total Score cut-off value of 70, the assessment shows high sensitivity (93%) and specificity (81%) (PPV 84%; NPV 90%).ConclusionsEarly motor behaviour assessed with the IMP is strongly associated with middle-term neurodevelopmental outcome. The present study confirms the concurrent validity of the IMP with the AIMS, its association with the GMA and its ability to reflect brain lesion load, hence contributing to the construct validity of the assessment.Trial registrationNCT01990183andNCT03234959(clinicaltrials.gov).
Selumetinib side effects in children treated for plexiform neurofibromas: first case reports of peripheral edema and hair color change
Authors: Baldo Francesco , Magnolato Andrea , Barbi Egidio , Bruno Irene 
Published: February 2021

Abstract
Background
Plexiform neurofibromas (PNs) are congenital tumors that affect around 50 % of the subjects with neurofibromatosis type 1. Despite being histologically benign, PNs can grow rapidly, especially in the pediatric age, and cause severe morbidities. In the past, various therapeutic approaches have been proposed to treat these masses, none of which obtained valuable results. Selumetinib, an inhibitor of mitogen-activated protein kinase (MEK) 1 and 2, has been the first molecule to demonstrate the ability of tackling the growth of PNs. The drug’s most common side effects, which usually are mild or moderate, include gastrointestinal symptoms (diarrhea, abdominal pain), dermatologic manifestations (maculo-papular and acneiform rash, paronychia, mucositis), and various laboratory test abnormalities (elevation of creatine kinase and aminotransferase).

Cases presentation
We report two previously undescribed adverse events in pediatric patients: peripheral edema and hair color change. The first case of peripheral edema occurred in a 7-year-old boy affected by a severe form of NF1, after two years of treatment with selumetinib at the standard dose (25 mg/m2twice a day). The edema involved the right leg, and the patient did not complain of pain. The second case of peripheral edema occurred in a 12-year-old girl after six months of therapy with selumetinib at the standard dose, involving her lower left leg. The patient initially complained of pain in that area, but it gradually and spontaneously resolved. In both patients, all the radiological exams, including lymphoscintigraphy, pelvic and abdominal ultrasound, and doppler ultrasound of the affected limb, as well as blood tests, revealed no abnormalities. Hair color change appeared in a 4-year-old boy after six months of therapy at the standard dose. The boy’s hair, whose natural color was dark blonde, became lighter in some areas. Despite the appearance of these side effects, all the patients and their families decided to continue the treatment with selumetinib, in considerations of its clinical benefits.

Conclusions
Since the use of selumetinib to treat plexiform neurofibromas is increasing in the pediatric population, clinicians should be aware of its side effects, so to decide whether continuing the treatment, reducing the dose or even interrupting it, when appropriate.
Mycoplasma hominis meningitis in an extremely preterm newborn: a case report
Authors: Ansari Najmus Sehr , Asztalos Elizabeth , Rolnitsky Asaph 
Published: February 2021

Abstract
Background
Mycoplasma Hominis is a micro-organism which is a part of the human genitourinary tract flora. Neonates are susceptible to acquire this pathogen either in utero or through vertical transmission. In rare cases, it may cause central nervous system infections with severe morbidity and mortality in preterm and term neonates.

Case presentation
We present a case of Mycoplasma Hominis meningitis in an extremely preterm neonate who presented with lethargy, tachycardia and seizures on day 7 of life. There was no history of maternal systemic or genitourinary infection during pregnancy and at the time of delivery. Empirical antibiotic therapy for neonatal meningitis was commenced after sending blood and cerebrospinal fluid cultures. Cerebrospinal fluid analysis showed pleocytosis with neutrophilic predominance, but no bacteria was identified on gram staining. Blood culture yielded no growth of any bacterial pathogen. However, growth of Mycoplasma Hominis was suspected in cerebrospinal fluid culture which was confirmed by 16S ribosomal ribonucleic acid (RNA) polymerase chain reaction analysis. Subsequently, antibiotics were changed to Moxifloxacin and Doxycycline which were given for a total duration of 6 weeks. Multiple cerebrospinal fluid cultures were performed during this treatment. No growth of any pathogen was identified on any of these cerebrospinal fluid cultures.

Conclusions
We report a rare case of Mycoplasma Hominis meningitis in an extremely preterm neonate which was successfully treated with a combination therapy of Moxifloxacin and Doxycycline.
It is important to consider the possibility of Mycoplasma Hominis meningitis in neonates who present with clinical signs and pleocytosis in cerebrospinal fluid but negative gram staining and no growth on conventional culture media.