bluuebunny/crossref_metadata_2025_split huggingface dataset:
Medulloblastoma: clinicopathological parameters, risk stratification, and survival analysis of immunohistochemically validated molecular subgroups
Authors: Eid Asmaa Mustafa , Heabah Nehal Abd El-Ghaffar 
Published: February 2021

Abstract
Background
Medulloblastoma (MB) is a heterogeneous disease, displaying distinct genetic profiles with specific molecular subgroups. This study aimed to validate MB molecular subgrouping using surrogate immunohistochemistry and associate molecular subgroups, histopathological types, and available clinicopathological parameters with overall survival (OS) and progression-free survival (PFS) of MB patients. This study included 40 MBs; immunohistochemical staining, using β-catenin and GRB2-Associated Binding Protein 1 (GAB1) antibodies, was used to classify MB cases into wingless signaling activated (WNT), sonic hedgehog (SHH), and non-WNT/SHH molecular subgroups. Nuclear morphometric analysis (for assessment of degree of anaplasia) and Kaplan-Meier survival curves were done.

Results
MB cases were classified into WNT (10%), SHH (30%), and non-WNT/SHH (60%) subgroups. Histopathological types differed significantly according to tumor location (p< 0.001), degree of anaplasia (p = 0.014), molecular subgroups (p < 0.001), and risk stratification (p = 0.008). Molecular subgroups differed significantly in age distribution (p = 0.031), tumor location (p< 0.001), histopathological variants (p < 0.001), and risk stratification (p < 0.001). OS was 77.5% and 50% after 1 and 2 years, while PFS was 65% and 27.5% after 1 and 2 years, respectively. OS and PFS were associated significantly with histopathological variants (p < 0.001 and 0.001), molecular subgroups (p = 0.012 and 0.005), and risk stratification (p < 0.001 and < 0.001), respectively.

Conclusions
Medulloblastoma classification based on molecular subgroups, together with clinicopathological indicators, mainly histopathological types; accurately risk stratifies MB patients and predicts their survival.
COVID-19 causing acute deterioration of interstitial lung disease: a case report
Authors: Kathar Hussain Mohamed Rafi , Kulasekaran N. , Anand A. M. , Danassegarane Padma Reka 
Published: February 2021

Abstract
Background
Interstitial lung disease (ILD) comprises a heterogeneous group of disorders characterized by multifocal diffuse lung involvement. Similarly, COVID-19 has varied multispectral organ involvement. Patients with underlying ILD and coexistent COVID-19 infection may lead to an acute blow to the already deceased lung.

Case presentation
A 58-year-old man presented with fever and cough with expectoration for the past 4 days associated with breathlessness. He was a smoker and alcoholic for the past 20 years. His saturation was low in room air around 84% and improved to 98% with 10 l/min of nasal oxygen. Further investigation shows acute deterioration of ILD.

Conclusion
COVID-19 infection has a spectrum of manifestations. Acute deterioration of ILD is rarely reported in the literature. Etiology should be investigated further.
A practice facilitation-guided intervention in primary care settings to reduce cardiovascular disease risk: a cost analysis
Authors: Gold Heather T. , Siman Nina , Cuthel Allison M. , Nguyen Ann M. , Pham-Singer Hang , Berry Carolyn A. , Shelley Donna R. 
Published: February 2021

AbstractBackgroundA stepped-wedge, cluster randomized controlled trial assessed the effectiveness of practice facilitation (PF) for adoption of guidelines for prevention and treatment of cardiovascular disease risk factors. This study estimated the associated cost of PF for guideline adoption in small, private primary care practices.MethodsThe cost analysis included categories for start-up costs, intervention costs, and practice staff costs for the implemented PF-guided intervention. We estimated the total 1-year costs to operate the program and calculated the mean and range of the cost-per-practice by quarter of the intervention. We estimated the lower and upper bounds for all salary expenses, rounding to the nearest $100.ResultsTotal 1-year intervention costs for all 261 practices ranged from $7,900,000 to $10,200,000, with program and practice salaries comprising $6,600,000–$8,400,000 of the total. Start-up costs were a small proportion (3%) of the total 1-year costs. Excluding start-up costs, quarter 1 cost-per-practice was the most expensive at $20,400–$26,700, and quarter 4 was the least expensive at about $10,000. Practice staff time (compared with program staff time) was the majority of the staffing costs at 75–84%.ConclusionsThe PF strategy costs approximately $10,000 per practice per quarter for program and practice costs, once implemented and running at highest efficiency. Whether this program is “worth it” to the decision-maker depends on the relative costs and effectiveness of their other options for improving cardiovascular risk reduction.Trial registrationThis study is retrospectively registered on January 5, 2016, atwww.clinicaltrials.govasNCT02646488.
Matrix metalloproteinase-9 gene polymorphism (-1562 C/T) and its correlation with diabetic nephropathy
Authors: Shalaby Kholoud , Bahriz Rania , Mahsoub Nancy , El-Arman Mohammed M. , El-Said Ghada 
Published: February 2021

AbstractBackgroundMatrix metalloproteinase 9 (MMP-9) is an important inflammatory marker in diabetic nephropathy. Many studies assessed the association between MMP-9 gene polymorphism and different microvascular complications of type 2 diabetes mellitus, though the results were inconclusive and need further exploration. Our study aimed to assess the association between MMP-9 -1562C/T gene polymorphism and diabetic nephropathy in patients with type 2 diabetes mellitus.ResultsTaking CC genotype of rs3918242 (MMP-9-1562C/T SNP) as the reference genotype and C as the reference allele, TT genotype, T allele showed significantly lower frequency in diabetic nephropathy group than without nephropathy (2.9% versus 20%, 20% versus 35.7% respectively), with the possible significant protective effect against diabetic nephropathy development (OR = 0.269, 0.450 respectively); it was considered as an independent predictor for diabetic nephropathy occurrence.ConclusionsThis study suggested that T allele of MMP-9 -1562C/T single nucleotide polymorphism had a protective role against diabetic nephropathy development and also had a role for early prediction of patients susceptible to this complication, so it helps in prevention and management of those patients.
Evaluating Readability Scores of Treatment Summaries and Cancer Survivorship Care Plans
Authors: Kue Jennifer , Klemanski Dori L. , Browning Kristine K. 
Published: February 2021

PURPOSE: Treatment Summaries and Survivorship Care Plans (TS/SCPs) may be difficult for patients to comprehend because of readability, magnitude of information, and complex medical verbiage. METHODS: Readability scores were calculated for TS/SCP templates including ASCO, Oncolink, Journey Forward, and the authors' institution. The Simple Measure of Gobbledygook (SMOG) index, Flesch-Kincaid reading grade level, Coleman-Liau Index, and Gunning Fog index were used to assess readability. RESULTS: The Flesch-Kincaid reading ease scores for the blank ASCO templates ranged from 47.4 to 53.3, requiring a reading grade level of 10-12. Coleman-Liau and Gunning Fog scores showed that an 11th grade reading level is essential, and SMOG required a college education to comprehend the ASCO templates. For the colorectal case exemplar, Oncolink's template resulted in the lowest SMOG score (11.3; 11th grade), Flesch-Kincaid reading grade level (11; 11th grade), and Coleman-Liau score (12; 12th grade). Journey Forward's TS/SCP template scored the highest on the SMOG (21.2; college graduate), Flesch-Kincaid reading grade level (18.3; college graduate), and Gunning-Fog index (25.8; college graduate) compared with other TS/SCPs. CONCLUSION: The existing TS/SCP templates used by US cancer centers are written at a grade level beyond the comprehension of most adults. Cancer care teams should assess TS/SCP content for readability and use of plain language and reduce medical jargon.
Pitfalls in Performing and Interpreting Inferior Petrosal Sinus Sampling: Personal Experience and Literature Review
Authors: Perlman Jordan E , Johnston Philip C , Hui Ferdinand , Mulligan Guy , Weil Robert J , Recinos Pablo F , Yogi-Morren Divya , Salvatori Roberto , Mukherjee Debraj , Gallia Gary , Kennedy Laurence , Hamrahian Amir H 
Published: February 2021

Abstract

Context
Inferior petrosal sinus sampling (IPSS) helps differentiate the source of ACTH-dependent hypercortisolism in patients with inconclusive biochemical testing and imaging, and is considered the gold standard for distinguishing Cushing disease (CD) from ectopic ACTH syndrome. We present a comprehensive approach to interpreting IPSS results by examining several real cases.

Evidence Acquisition
We performed a comprehensive review of the IPSS literature using PubMed since IPSS was first described in 1977.

Evidence Synthesis
IPSS cannot be used to confirm the diagnosis of ACTH-dependent Cushing syndrome (CS). It is essential to establish ACTH-dependent hypercortisolism before the procedure. IPSS must be performed by an experienced interventional or neuroradiologist because successful sinus cannulation relies on operator experience. In patients with suspected cyclical CS, it is important to demonstrate the presence of hypercortisolism before IPSS. Concurrent measurement of IPS prolactin levels is useful to confirm adequate IPS venous efflux. This is essential in patients who lack an IPS-to-peripheral (IPS:P) ACTH gradient, suggesting an ectopic source. The prolactin-adjusted IPS:P ACTH ratio can improve differentiation between CD and ectopic ACTH syndrome when there is a lack of proper IPS venous efflux. In patients who have unilateral successful IPS cannulation, a contralateral source cannot be excluded. The value of the intersinus ACTH ratio to predict tumor lateralization may be improved using a prolactin-adjusted ACTH ratio, but this requires further evaluation.

Conclusion
A stepwise approach in performing and interpreting IPSS will provide clinicians with the best information from this important but delicate procedure.
Novel Recurrent Altered Genes in Chinese Patients With Anaplastic Thyroid Cancer
Authors: Zhang Lingyun , Ren Zhixiang , Su Zhengzheng , Liu Yang , Yang Tian , Cao Minyuan , Jiang Yong , Tang Ying , Chen Haining , Zhang Weihan , Gong Rixiang , Wei Tao , Peng Yong , Liu Bo , Zhang Wei , Yang Li , Hu Yiguo , Li Zhihui , Zhu Jingqiang , Xu Heng , Shu Yang , Luo Han 
Published: February 2021

Abstract

Background
Anaplastic thyroid cancer (ATC) is a rare but lethal malignancy, and few systematic investigations on genomic profiles of ATC have been performed in Chinese patients.

Methods
Fifty-four ATC patients in West China Hospital between 2010 to 2020 were retrospectively analyzed, while 29 patients with available samples were sequenced by whole-exome sequencing (WES). The associations between genomic alterations and clinical characteristics were statistically evaluated.

Results
The median overall survival was 3.0 months in the entire cohort, which was impacted by multiple clinical features, including age, tumor size, and different treatment strategies. In the WES cohort, totally 797 nonsilent mutations were detected; the most frequently altered genes were TP53 (48%), BRAF (24%), PIK3CA (24%), and TERT promoter (21%). Although these mutations have been well-reported in previous studies, ethnic specificity was exhibited in terms of mutation frequency. Moreover, several novel significantly mutated genes were identified including RBM15 (17%), NOTCH2NL (14%), CTNNA3 (10%), and KATNAL2 (10%). WES-based copy number alteration analysis also revealed a high frequent gain of NOTCH2NL (41%), which induced its increased expression. Gene mutations and copy number alterations were enriched in phosphatidylinositol 3-kinase/AKT/mechanistic target of rapamycin (mTOR), NOTCH, and WNT pathways.

Conclusions
This study reveals shared and ethnicity-specific genomic profiles of ATC in Chinese patients and suggests NOTCH2NL may act as a novel candidate driver gene for ATC tumorigenesis.
In Men With Obesity, T2DM Is Associated With Poor Trabecular Microarchitecture and Bone Strength and Low Bone Turnover
Authors: Vigevano Francesca , Gregori Giulia , Colleluori Georgia , Chen Rui , Autemrongsawat Vimlin , Napoli Nicola , Qualls Clifford , Villareal Dennis T , Armamento-Villareal Reina 
Published: February 2021

Abstract

Introduction
Obesity and type 2 Diabetes (T2D) are both associated with greater bone mineral density (BMD) but increased risk of fractures. The effect of the combination of both conditions on bone metabolism, microarchitecture, and strength in the obese population remains unknown.

Methods
Data from 112 obese men were collected. Bone turnover and biochemical markers were measured by enzyme-linked immunosorbent assay, body composition and BMD at all sites were assessed by dual energy X-ray absorptiometry, whereas bone microarchitecture and strength (stiffness and failure load) were measured by high-resolution peripheral computed tomography. Data were compared among metabolically healthy obese (MHO) and metabolically unhealthy obese (MUHO) with and without T2D and between obese without and with T2D.

Results
Compared to MHO and MUHO without T2D, MUHO with T2D had significantly lower levels of osteocalcin ((7.49 ± 3.0 and 6.03 ± 2.47 vs 4.24 ± 2.72 ng/mL, respectively, P = 0.003) and C-terminal telopeptide of type I collagen (CTx) (0.28 ± 0.10 and 0.29 ± 0.13 vs 0.21 ± 0.15 ng/mL, respectively, P = 0.02). Dividing our subjects simply into those with and without T2D showed that obese men with T2D had significantly lower levels of osteocalcin (P = 0.003) and CTx (P = 0.005), greater trabecular separation at the tibia and radius (P = 0.03 and P = 0.04, respectively), and lower tibial failure load and stiffness (both P = 0.04), relative to obese men without T2D.

Conclusion
In men, the combination of obesity and T2D is associated with reduced bone turnover and poorer trabecular bone microarchitecture and bone strength compared to those who are obese but without T2D, suggesting worse bone disease.
The Influence of Prepubertal Onset of Type 1 Diabetes and Age of Menarche on Polycystic Ovary Syndrome Diagnosis
Authors: Łebkowska Agnieszka , Adamska Agnieszka , Krentowska Anna , Uruska Aleksandra , Rogowicz-Frontczak Anita , Araszkiewicz Aleksandra , Ożegowska Katarzyna , Hryniewicka Justyna , Leśniewska Monika , Wender-Ożegowska Ewa , Zozulińska-Ziółkiewicz Dorota , Kowalska Irina 
Published: February 2021

Abstract

Context
Higher prevalence of polycystic ovary syndrome (PCOS) in women with type 1 diabetes (T1DM) is linked to exogenous insulin, especially when diabetes is diagnosed before puberty.

Objective
The study evaluates the impact of prepubertal onset of T1DM and insulin therapy on PCOS diagnosis and phenotypic characteristics in women with T1DM.

Design, Setting, and Patients
We studied 83 women with T1DM (age 26 ± 5 years, BMI 24 ± 3 kg/m2) 36 with premenarchal (PM) onset of T1DM [17 with PCOS diagnosed (PCOS+PM) and 19 without PCOS (noPCOS+PM)] and 47 women with postmenarchal onset of T1DM [24 with PCOS (PCOS-noPM) and 23 without PCOS (noPCOS-noPM)].

Outcome Measurements
Clinical examination, assessment of serum sex hormones, glycated hemoglobin (HbA1c) and ultrasonographic evaluation of the ovaries were performed in all women.

Results
Applying Rotterdam criteria, 49% of women with T1DM were diagnosed with PCOS. There were no differences in hormonal profile and ovarian parameters between PCOS+PM and PCOS-noPM. Women with T1DM+PM had higher insulin dose/24 h and U/kg bw/24 h than T1DM-noPM (P-values = 0.014 and 0.001, respectively). Both PCOS+PM and noPCOS+PM groups had higher insulin dose U/kg bw/24 h in comparison to PCOS-noPM (P-values = 0.004 and = 0.006, respectively). In multivariable logistic regression analysis, age of menarche [odds ratio (OR): 0.672; 95% confidence interval (CI): 0.465-0.971] and HbA1c (OR: 0.569; 95% CI: 0.383-0.846) were associated with the diagnosis of PCOS.

Conclusions
There were no differences in the prevalence of PCOS between T1DM+PM and T1DM-noPM; however, earlier menarche might have an influence on PCOS diagnosis in women with T1DM.
Efficacy and Safety of Dulaglutide in Older Patients: A post hoc Analysis of the REWIND trial
Authors: Riddle Matthew C , Gerstein Hertzel C , Xavier Denis , Cushman William C , Leiter Lawrence A , Raubenheimer Peter J , Atisso Charles M , Raha Sohini , Varnado Oralee J , Konig Manige , Lakshmanan Mark , Franek Edward 
Published: February 2021

Abstract

Context
Dulaglutide reduced major adverse cardiovascular events (MACE) in the Researching Cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) trial. Its efficacy and safety in older vs younger patients have not been explicitly analyzed.

Objective
This work aimed to assess efficacy and safety of dulaglutide vs placebo in REWIND by age subgroups (≥ 65 and &lt; 65 years).

Methods
A post hoc subgroup analysis of REWIND was conducted at 371 sites in 24 countries. Participants included type 2 diabetes patients aged 50 years or older with established cardiovascular (CV) disease or multiple CV risk factors, and a wide range of glycemic control. Patients were randomly assigned (1:1) to dulaglutide 1.5 mg or placebo as an add-on to country-specific standard of care. Main outcomes measures included MACE (first occurrence of the composite of nonfatal myocardial infarction, nonfatal stroke, or death from CV or unknown causes).

Results
There were 5256 randomly assigned patients who were 65 years or older (mean = 71.0), and 4645 were younger than 65 years (mean = 60.7). Baseline characteristics were similar in randomized treatment groups. Dulaglutide treatment showed a similar reduction in the incidence (11% vs 13%) of MACE in older vs younger patients. The rate of permanent study drug discontinuation, incidence of all-cause mortality, hospitalizations for heart failure, severe hypoglycemia, severe renal or urinary events, and serious gastrointestinal events were similar between randomized treatment groups within each age subgroup. The incidence rate of serious cardiac conduction disorders was numerically higher in the dulaglutide group compared to placebo within each age subgroup but the difference was not statistically significant.

Conclusion
Dulaglutide had similar efficacy and safety in REWIND in patients65 years and older and those younger than 65 years.
Stem cell quiescence: the challenging path to activation
Authors: Urbán Noelia , Cheung Tom H. 
Published: February 2021

ABSTRACT
Quiescence is a cellular state in which a cell remains out of the cell cycle but retains the capacity to divide. The unique ability of adult stem cells to maintain quiescence is crucial for life-long tissue homeostasis and regenerative capacity. Quiescence has long been viewed as an inactive state but recent studies have shown that it is in fact an actively regulated process and that adult stem cells are highly reactive to extrinsic stimuli. This has fuelled hopes of boosting the reactivation potential of adult stem cells to improve tissue function during ageing. In this Review, we provide a perspective of the quiescent state and discuss how quiescent adult stem cells transition into the cell cycle. We also discuss current challenges in the field, highlighting recent technical advances that could help overcome some of these challenges.
TRIP6 is required for tension at adherens junctions
Authors: Venkatramanan Srividya , Ibar Consuelo , Irvine Kenneth D. 
Published: February 2021

ABSTRACT
Hippo signaling mediates influences of cytoskeletal tension on organ growth. TRIP6 and LIMD1 have each been identified as being required for tension-dependent inhibition of the Hippo pathway LATS kinases and their recruitment to adherens junctions, but the relationship between TRIP6 and LIMD1 was unknown. Using siRNA-mediated gene knockdown, we show that TRIP6 is required for LIMD1 localization to adherens junctions, whereas LIMD1 is not required for TRIP6 localization. TRIP6, but not LIMD1, is also required for the recruitment of vinculin and VASP to adherens junctions. Knockdown of TRIP6 or vinculin, but not of LIMD1, also influences the localization of myosin and F-actin. In TRIP6 knockdown cells, actin stress fibers are lost apically but increased basally, and there is a corresponding increase in the recruitment of vinculin and VASP to basal focal adhesions. Our observations identify a role for TRIP6 in organizing F-actin and maintaining tension at adherens junctions that could account for its influence on LIMD1 and LATS. They also suggest that focal adhesions and adherens junctions compete for key proteins needed to maintain attachments to contractile F-actin.
Septins coordinate cell wall integrity and lipid metabolism in a sphingolipid-dependent process
Authors: Mela Alexander , Momany Michelle 
Published: February 2021

ABSTRACT
Septins colocalize with membrane sterol-rich regions and facilitate recruitment of cell wall synthases during wall remodeling. We show that null mutants missing an Aspergillus nidulans core septin present in hexamers and octamers (ΔaspAcdc11, ΔaspBcdc3 or ΔaspCcdc12) are sensitive to multiple cell wall-disturbing agents that activate the cell wall integrity MAPK pathway. The null mutant missing the octamer-exclusive core septin (ΔaspDcdc10) showed similar sensitivity, but only to a single cell wall-disturbing agent and the null mutant missing the noncore septin (ΔaspE) showed only very mild sensitivity to a different single agent. Core septin mutants showed changes in wall polysaccharide composition and chitin synthase localization. Mutants missing any of the five septins resisted ergosterol-disrupting agents. Hexamer mutants showed increased sensitivity to sphingolipid-disrupting agents. Core septins mislocalized after treatment with sphingolipid-disrupting agents, but not after ergosterol-disrupting agents. Our data suggest that the core septins are involved in cell wall integrity signaling, that all five septins are involved in monitoring ergosterol metabolism, that the hexamer septins are required for sphingolipid metabolism and that septins require sphingolipids to coordinate the cell wall integrity response.
Is Exercise a Cost-Effective Intervention for People Receiving Hemodialysis? A Narrative Review
Authors: Hurt Adam W. , March Daniel S. , Cooper Nicola J. , Burton James O. 
Published: February 2021

ABSTRACT
Chronic kidney disease is associated with elevated cardiovascular morbidity and mortality, which is particularly high in individuals with end-stage kidney disease receiving hemodialysis and leads to a disproportionate use of health care services. Although exercise is recommended for these patients, specific programs of exercise are yet to be implemented as part of routine care, which may be partly due to uncertainty over the cost-effectiveness of such programs. Within the current climate of limited funding and resources, health care providers are increasingly under pressure to ensure new treatments are cost-effective. Exercise programs have demonstrated some benefit to physical function and quality of life when used as part of the management of end-stage kidney disease. This may lead to reductions in the growing patient costs and hospitalizations, and improve quality of life. However, the cost-effectiveness of programs of exercise in this population has not been previously reported. Therefore, the objectives of this review are to describe cost-effectiveness, to highlight the potential for exercise programs to be cost-effective in this population, and to identify some future directions.