bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and molecular analysis of smoothened inhibitors in Sonic Hedgehog medulloblastoma
Authors: Pereira Victor , Torrejon Jacob , Kariyawasam Dulanjalee , Berlanga Pablo , Guerrini-Rousseau Léa , Ayrault Olivier , Varlet Pascale , Tauziède-Espariat Arnault , Puget Stéphanie , Bolle Stéphanie , Beccaria Kevin , Blauwblomme Thomas , Brugières Laurence , Grill Jacques , Geoerger Birgit , Dufour Christelle , Abbou Samuel 
Published: July 2021

Abstract

Background
Smoothened inhibitors (SMOi) have shown activity in Sonic Hedgehog (SHH) medulloblastoma, however this therapeutic class was not developed in children due to severe effects reported on growth. We hereby report long-term follow-up of young patients treated with SMOi for recurrent medulloblastoma.

Methods
Clinical data on response and toxicity from patients treated with vismodegib or sonidegib from 2011 to 2019 for a SHH medulloblastoma were retrospectively reviewed. Methylation analysis and whole exome sequencing were performed whenever possible.

Results
All patients with a somatic PTCH1 mutation responded to SMOi (6/8), including 2 prolonged complete responses. One patient was free of disease 8.2 years after treatment. SMOi was challenged again for 3 patients. Two of them had a response, one with SMOi alone, the other one in combination with temozolomide despite previous progression under monotherapy. SMO resistance mutations were found in patients from biopsy at relapse. Combination with temozolomide or surgery plus radiotherapy was associated with very long disease control in 2 patients. The most severe adverse events were myalgia and growth plate fusion with metaphyseal sclerosis. Normal growth velocity was recovered for 1 patient although her final height was below estimated target height.

Conclusions
Targeting SMO in mutated PTCH1 is an interesting strategy for long-term responses. Combination of SMOi with chemotherapy or surgery and local radiotherapy is an appealing strategy to prevent early resistance and diminish SMOi exposure, especially in young patients. Inhibition of SHH pathway causes growth and development impairment but partial recovery of the growth velocity is possible.
Partial substitution of fish oil for linseed oil enhances beneficial fatty acids from rumen biohydrogenation but reduces ruminal fermentation and digestibility in growing goats
Authors: Thanh Lam Phuoc , Phakachoed Noppharat , Suksombat Wisitiporn , Loor Juan J , Hang Tran Thi Thuy 
Published: July 2021

Abstract
This study was performed to investigate effects of partial replacement of fish oil (FO) for linseed oil (LO) on digestibility, ruminal fermentation and biohydrogenation in growing goats. Experiment 1 was carried out in four growing male goats aged 6 months in a 4 × 4 Latin square design. Goats were fed a basal diet supplemented with 25 g/kg dry matter either LO alone or in combination with tuna FO. Treatments were developed by replacing FO for LO at ratios of 0, 5, 10 and 15 g/kg DM corresponding to FO-0, FO-5, FO-10 and FO-15, respectively. Experiment 2 was carried out in an in vitro incubation system including 12 fermenters with the same four treatments. Each fermenter consisted of 40 mL goat ruminal fluid, 160 mL warm buffer, 2 g mixed substrates, and 50 mg FO-0, FO-5, FO-10 or FO-15. Fish oil inclusion reduced (P &lt; 0.05) digestibility and nitrogen retention in Experiment 1. Increasing doses of FO in the diet induced a strong drop (P &lt; 0.001) in ruminal total volatile fatty acid (VFA) concentration and protozoa population at 3 h post incubation, but did not affect individual VFA proportions. Substitution of FO for LO decreased mean concentrations of C18:0 (P = 0.057), c-9,c-12 C18:2 and C18:3n-3 (P &lt; 0.001), but increased (P &lt; 0.001) C20:5n-3 and C22:6n-3. Feeding FO-10 enhanced formation of ruminal c-9,t-11 conjugated linoleic acid (CLA) concentration compared with FO-0. Overall, combined data suggest that to improve ruminal concentrations of C20:5n-3, C22:6n-3, and c-9,t-11 CLA for deposition in tissues or milk with minimal risk of affecting digestibility and ruminal fermentation, a dietary supplementation of 15 g/kg LO and 10 g/kg FO would be suitable.
What Role Should Resistance Play in Training Health Professionals?
Authors: Ellaway Rachel H. , Wyatt Tasha R. 
Published: July 2021

The role that resistance plays in medicine and medical education is ill-defined. Although physicians and students have been involved in protests related to the COVID-19 pandemic, structural racism, police brutality, and gender inequity, resistance has not been prominent in medical education’s discourses, and medical education has not supported students’ role and responsibility in developing professional approaches to resistance. While learners should not pick and choose what aspects of medical education they engage with, neither should their moral agency and integrity be compromised. To that end, the authors argue for professional resistance to become a part of medical education.
This article sets out a rationale for a more explicit and critical recognition of the role of resistance in medical education by exploring its conceptual basis, its place both in training and practice, and the ways in which medical education might more actively embrace and situate resistance as a core aspect of professional practice. The authors suggest different strategies that medical educators can employ to embrace resistance in medical education and propose a set of principles for resistance in medicine and medical education.
Embracing resistance as part of medical education requires a shift in attention away from training physicians solely to replicate and sustain existing systems and practices and toward developing their ability and responsibility to resist situations, structures, and acts that are oppressive, harmful, or unjust.
Understanding How Semantic Structures of Individuals With Drug Addiction Transform As a Key to Effective Psychotherapy
Authors: Garifullin Ramil R. 
Published: July 2021

Objectives:
Semantic structures, sense-bearing elements, and values of a personality have been widely recognized as important factors in the treatment of patients with drug addiction. This research aims to enhance our understanding of transformations that occur in the system of values of drug-dependent patients, and to identify the values that need to be corrected during drug addiction psychotherapy.

Methods:
The values of 220 male patients with drug addiction aged between 20 and 60 years were studied by analyzing their verbal reactions and emotions expressed during conversations and by neurolinguistic programming.

Results:
The results of the statistical analysis showed that patients with drug addiction have basic values (learned during the normal life experience) that give way to values associated with the drug addiction experience, which is, however, simply gained and not lived through. Their system of values centers on drugs and drug intoxication.
In this research, drug addiction was viewed from the perspective of the semantic (sense-based) approach, which made it possible to develop some recommendations for effective psychotherapy of individuals with drug addiction based on their semantic structures.

Conclusion:
The psychotherapy of patients with drug addiction becomes effective when they are provided with a key value, that is, a value of their life experience, that is strong enough to replace the values of their drug-related experience.
Surgical Reduction of Spondylolisthesis During Lumbar Fusion
Authors: Lambrechts Mark J. , Barber Joshua A. , Beckett Nathan , Smith Caleb J. , Li Jinpu , Goldstein Christina L. , Leary Emily V. , Cook James L. , Choma Theodore J. 
Published: July 2021

Study Design:
This was a retrospective cohort study.

Objective:
The objective of this study was to quantify the rates of complication following surgical treatment for symptomatic degenerative and isthmic spondylolisthesis and to examine the association between slip reduction and complication rates.

Summary of Background Data:
It is unclear if the degree of spondylolisthesis reduction during lumbar spine fusion in adults influences the rate of surgical complications.

Methods:
This is a retrospective cohort study of 1-level and 2-level adult fusion patients with degenerative or isthmic spondylolisthesis. The degree of reduction and complications were calculated, and complication rates between those with and without reduction were compared.

Results:
The surgical reduction was improved by 1 Meyerding grade in 56.5% of the 140 patients included in this analysis. Of those patients, 60% had a grade 1 spondylolisthesis. In addition, 62.5% of grade 2 slips had an improvement by 1 grade. Surgical reduction during lumbar fusion did not result in a higher rate of complications compared with in situ fusion.

Conclusions:
During 1-level or 2-level lumbar fusion for degenerative or isthmic spondylolisthesis, a 1-grade reduction of the slip was achieved in 56% of patients in this retrospective case series. Reduction of the spondylolisthesis was not associated with a higher rate of complication when compared with in situ fusion.

Level of Evidence:
Level IV.
Stromal α-Smooth Muscle Actin Positivity Is Associated With High-Risk Basal Cell Carcinomas
Authors: Krum dos Santos Ana Carolina , Lima Darlan , Marchiori Bakos Renato , da Silva Cartell André , Rangel Bonamigo Renan 
Published: July 2021

Abstract:
The presence of myofibroblast differentiation has been proposed as an invading mechanism in basal cell carcinomas. However, small studies regarding α-smooth muscle actin positivity have led to conflicting results. This review of 100 cases examines the association between α-smooth muscle actin positivity on immunohistochemical studies and the clinical and histopathological characteristics of the tumor, including tumor size, thickness, subtype, topography, ulceration, 5-year recurrence rate, and age at diagnosis.
Follicular T-Helper Cells in Marginal Zone Lymphoma: Evidence of an Organoid Immune Response
Authors: Robson Alistair , Bakr Farrah , Rashidghamat Ellie , Willsmore Zena N. , Ally Mina , Greenblatt Danielle , Barlow Richard , Wain E. Mary , Child Fiona , Esdaile Ben , Kempf Werner 
Published: July 2021

Introduction:
Primary cutaneous marginal zone B-cell lymphoma (MZL) follows an indolent clinical course. Histopathologically, there is a polymorphous infiltrate that includes small lymphocyte-like and centrocyte-like B cells and plasma cells usually with a substantial T-cell fraction. Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder, in which the signature cells have a follicular T-helper (TFH) phenotype and are admixed with numerous B cells. Thus, both present histologies of combined B-cell and T-cell infiltrates and represent differential diagnoses. The presence of TFH in MZL has yet to be elucidated.

Methods:
Forty-one biopsies from 40 cases of MZL and 7 cases of lymphoid hyperplasia cutis (LCH) were stained with antibodies to follicular T-helper cells, including Bcl-6, PD-1, ICOS, and CD10, as part of their diagnostic workup, were reviewed, and the stained slides were evaluated semiquantitively. Five reactive lymph nodes were also evaluated as controls.

Results:
All cases of MZL and LCH contained TFH, albeit usually in low proportions. There were repeated differences in levels of expression between TFH markers, with PD1 and Bcl-6 being the most prevalent. The pattern of involvement in MZL and LCH closely mirrored that observed in the reactive lymph nodes.

Conclusion:
MZL includes TFH cells, similar to reactive lymph nodes, and a complexity of cell types. This provides evidence of an organoid immune response challenging its simple categorization as a malignancy.
The Role of Antisense Therapies Targeting Lipoprotein(a)
Authors: Plakogiannis Roda , Sorbera Maria , Fischetti Briann , Chen Mandy 
Published: July 2021

Abstract:
Atherosclerotic cardiovascular disease (ASCVD) continues to be the leading cause of preventable death in the United States. Elevated low-density lipoprotein cholesterol (LDL-C) is well known to result in cardiovascular disease. Mainstay therapy for reducing LDL-C and ASCVD risk is statin therapy. Despite achieving desired LDL-C levels with lipid-lowering therapy, cardiovascular residual risk often persists. Elevated lipoprotein(a) [Lp(a)] levels have been highlighted as an inherent independent predictor of ASCVD, and decreasing Lp(a) levels may result in a significant reduction in the residual risk in high-risk patients. To date, there are no approved medications to lower Lp(a) levels. Nicotinic acid, proprotein convertase subtilisin/kexin 9 inhibitors, and antisense oligonucleotide have demonstrated modest to potent Lp(a) reduction. Spotlight has been placed on antisense oligonucleotides and their role in Lp(a) lowering. APO(a)LRx is in the frontline for selectively decreasing Lp(a) concentrations and ongoing research may prove that this medication may lower Lp(a)-mediated residual risk, translating into cardiovascular benefit.
Impact of stroke work on the ability of left ventricular mass to account for pressure effects on function in a community with prevalent systemic flow-dependent hypertension
Authors: Bello Hamza , Woodiwiss Angela J. , Naran Ravi , Peterson Vernice R. , Libhaber Carlos D. , Mmopi Keneilwe N. , Mthembu Nonhlanhla , Masiu Mohlabani , Da Silva Fernandes Daniel , Bamaiyi Adamu J. , Peters Ferande , Sareli Pinhas , Norton Gavin R. 
Published: July 2021

Aims:
To determine whether the confounding influence of stroke work on left ventricular mass (LVM) limits the ability of LVM to detect hypertensive LV dysfunction in systemic flow-dependent hypertension.

Methods:
In a community with prevalent systemic flow-dependent hypertension (n = 709), arterial haemodynamics, LVM and LV function were determined using central arterial pressure, aortic velocity and diameter measurements in the outflow tract, and echocardiography with tissue Doppler imaging.

Results:
In multivariate models, stroke work showed markedly stronger relations with LVM index (LVMI) than blood pressure load [central arterial SBP (SBPc), backward wave pressure (Pb), 24-h SBP] (P < 0.0001 for comparisons). In contrast, although SBPc, Pb, and 24-h SBP were inversely associated with myocardial tissue shortening (s’) and lengthening (e’) velocity, stroke work was not. With adjustments for stroke work, positive relationships between SBPc, Pb, or 24-h SBP and LVMI were eliminated (P = 0.20 to P = 0.89), but strong relations between BP and s’, e’ or E/e’ (P = 0.009 to P < 0.0001) remained. In mediation analysis, stroke work fully accounted for BP effects on LVMI, but explained none of the effects of BP on LV function. Hence LVMI accounted for little of the impact of BP load on LV function. Although LVMI beyond stroke work (inappropriate LVM) improved on relations between LVMI and s’, it failed to improve on relations with e’ or E/e’ and contributed little beyond LVMI to the impact of BP on LV function.

Conclusion:
In systemic flow-dependent hypertension, the impact of stroke work markedly limits the ability of LVM to account for adverse effects of hypertension on LV function.
Systemic retinal biomarkers
Authors: Ranchod Tushar M. 
Published: July 2021

Purpose of review
Systemic retinal biomarkers are biomarkers identified in the retina and related to evaluation and management of systemic disease. This review summarizes the background, categories and key findings from this body of research as well as potential applications to clinical care.

Recent findings
Potential systemic retinal biomarkers for cardiovascular disease, kidney disease and neurodegenerative disease were identified using regression analysis as well as more sophisticated image processing techniques. Deep learning techniques were used in a number of studies predicting diseases including anaemia and chronic kidney disease. A virtual coronary artery calcium score performed well against other competing traditional models of event prediction.

Summary
Systemic retinal biomarker research has progressed rapidly using regression studies with clearly identified biomarkers such as retinal microvascular patterns, as well as using deep learning models. Future systemic retinal biomarker research may be able to boost performance using larger data sets, the addition of meta-data and higher resolution image inputs.
Adult retinopathy of prematurity: treatment implications, long term sequelae, and management
Authors: Chang Emmanuel , Rao Prethy 
Published: July 2021

Purpose of review
Classically, ROP has been considered a neonatal disease only; however, pediatric ophthalmologists and retinal specialists worldwide are recently facing a new paradigm shift. retinopathy of prematurity (ROP) is now considered a lifelong disease that extends well into adulthood. The purpose of this review is to describe the adult ROP anatomy and discuss the late sequelae and management of this disease.

Recent findings
Neonatal ROP treatments affect both anterior and posterior segment anatomy. Anterior segment changes secondary to inflammation and posterior ciliary nerve ablation range from acute to chronic pathology, including cataract, secondary glaucoma, and corneal decompensation. Persistent avascular retina can be present in previously treated Type 1 ROP eyes after anti-vascular endothelial growth factor or in ’normal’ untreated eyes that did not previously meet Type 1 ROP criteria. Persistent avascular retina is associated with lattice-like changes, retinal tears, and detachments. The location and extent of the ridge, posterior hyaloidal contraction and adhesion, and persistent avascular retina all contribute to a spectrum of findings ranging from reactivation of neovascularization, tractional, rhegmatogenous, or exudative detachments.

Summary
Understanding Adult ROP anatomy is critical in identification of retinal pathology and treatment choice. ROP patients require lifelong monitoring.
Prevalence of Female and Male Athlete Triad Risk Factors in Ultramarathon Runners
Authors: Høeg Tracy Beth , Olson Emily Miller , Skaggs Kira , Sainani Kristin , Fredericson Michael , Roche Megan , Kraus Emily 
Published: July 2021

Objective:
To identify the prevalence of male and female athlete triad risk factors in ultramarathon runners and explore associations between sex hormones and bone mineral density (BMD).

Design:
Multiyear cross-sectional study.

Setting:
One hundred-mile ultramarathon.

Participants:
Competing runners were recruited in 2018 and 2019.

Assessment of Risk Factors:
Participants completed a survey assessing eating behaviors, menstrual history, and injury history; dual-energy x-ray absorptiometry for BMD; and laboratory evaluation of sex hormones, vitamin D, and ferritin (2019 cohort only).

Main Outcome Measure:
A Triad Cumulative Risk Assessment Score was calculated for each participant.

Results:
One hundred twenty-three runners participated (83 males and 40 females, mean age 46.2 and 41.8 years, respectively). 44.5% of men and 62.5% of women had elevated risk for disordered eating. 37.5% of women reported a history of bone stress injury (BSI) and 16.7% had BMD Z scores <−1.0. 20.5% of men had a history of BSI and 30.1% had Z-scores <−1.0. Low body mass index (BMI) (<18.5 kg/m2) was seen in 15% of women and no men. The Triad Cumulative Risk Assessment classified 61.1% of women and 29.2% of men as moderate risk and 5.6% of both men and women as high risk.

Conclusions:
Our study is the first to measure BMD in both male and female ultramarathon runners. Our male population had a higher prevalence of low BMD than the general population; females were more likely to report history of BSI. Risk of disordered eating was elevated among our participants but was not associated with either low BMD or low BMI.
The justification for the progressive fibrotic phenotype
Authors: Kolb Martin RJ. , Flaherty Kevin R. 
Published: July 2021

Purpose of review
Describe the concept and recent data for the concept of progressive fibrotic interstitial lung disease (ILD).

Recent findings
Making an accurate diagnosis is critical to help determine appropriate therapy and predict prognosis. This is certainly true in the field of ILD where a diagnosis of idiopathic pulmonary fibrosis (IPF) leads a clinician to consider initiation of antifibrotic therapy, and avoidance of immunosuppression due to possible harm, at the time of diagnosis due to the high probability of disease progression. In other types of ILD immunosuppression may be helpful such as those associated with a connective tissue disease or in combination with antigen avoidance in hypersensitivity pneumonia. It is also recognized that despite initial approaches to therapy some non-IPF ILDs will develop progressive fibrosis leading to increased symptoms, decreased quality of life and early mortality. Once fibrosis is present, the biologic pathways responsible for progression can be redundant and respond in a similar fashion to antifibrotic therapy independent of the underlying disease.

Summary
There are clinical and biological rationale for the justification of a progressive fibrotic phenotype that complements the therapeutic decisions and prognosis provided by initial diagnosis.
Disease state prediction for 2019 novel coronavirus (COVID-19) pneumonia using CT manifestations and body temperature dynamic analysis
Authors: Liang Pan , Wang Rui , Ren Xiu-chun , Huang Wen-peng , Gao Jian-bo 
Published: July 2021

Abstract
2019 Novel Coronavirus (COVID-19) is a new acute infectious disease of respiratory system, posed a great threat to human health because of its strong infectivity and rapid progress. This study aimed to assess the severity of COVID-19 Pneumonia by analyzing the change of CT manifestations and body temperature.
This retrospective review included 22 patients with COVID-19 pneumonia. The imaging manifestations and clinical features were observed and evaluated.
Most of the infected patients were men (13/22, 59%). Fever (>38°C) (17/22, 77%) and cough (6/22, 27%) were the main symptoms. Leukocytes count decreased in 23% of patients and lymphocyte decreased in 41%. Twenty-one patients with pneumonia had abnormal findings on chest CT. The special CT manifestations were observed at the first CT examination when the lesions progressed, including a single ground glass nodule with uneven density, multiple ground glass opacities distributed in subpleural, and the ground glass opacities confined in superior lobe. The special CT manifestations were observed at the first CT examination when the lesions resolved, including ground glass opacities with homogeneous density. The lesion involved in the bilateral lungs and the absorption of the lesions mainly occurred in bilateral inferior lobes. Three patients had normalized body temperature increased more than 1°C within 1 to 2 days after admission. Ten patients fluctuated more than 1°C within 1 to 7 days after admission and the second CT scans showed the disease was at the progressive stage.
Dynamic analysis of CT manifestations and body temperature have the potential to predict the severity of COVID-19 pneumonia.