bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of MAPK/ERK signalling in Merlin-null Schwann cells leads to increased and sustained immune cell infiltration in the peripheral nervous system
Authors: Woodhouse Evyn , Laraba Liyam , Lespade Charlotte , Srotyr Marie , Lloyd Alison C , Parkinson David B 
Published: October 2021

Abstract

Aims
Previous work has shown that increased numbers of macrophages are associated with more rapid schwannoma tumour growth and we are interested in signals that control entry of macrophages and other immune cells into these tumours. Activation of the Raf-kinase domain and the Raf/MEK/ERK pathway within Schwann cells has been observed to induce an inflammatory response in peripheral nerves in the absence of injury. Activation of an inducible Raf-kinase transgene in Schwann cells allows modelling of acute demyelination of peripheral nerves without nerve injury. This Raf-oestrogen receptor fusion protein (Raf-TR) is activated by the oestrogen analogue Tamoxifen and so allows targeted, controlled activation of the Raf/MEK/ERK pathway within the Schwann cells.
Here, in order to understand drivers of tumour formation, we assess the effect of MAPK activation in Merlin-null Schwann cells upon immune cell infiltration within the PNS.

Method
RafTR-P0CRE-NF2fl/fl mice of 4-6 weeks age were injected daily (IP) with 2mg of 4-hydroxy-tamoxifen or vehicle (corn oil) control for 5 consecutive days. RafTR was activated on either a Merlin (NF2) wild-type (NF2 fl/fl, P0-CRE-) or NF2 null (NF2 fl/fl, P0-CRE+) background and effects on immune cell infiltration studied in each condition.
Immunofluorescence was performed in the dorsal root ganglia (DRGs) and sciatic nerves of mice to identify various immune cell infiltrates at various timepoints. These will include neutrophils, mast cells, T-Cells and macrophages using the cell markers Csf3r, C-kit, CD3 and IBA1 respectively.

Results
At 21 days post treatment, a significantly increased infiltration of macrophages within the sciatic nerve and dorsal root ganglia was observed in mice treated with Tamoxifen when compared to vehicle controls. Loss of NF2 led to a massive increase in the number of macrophages recruited to peripheral nerves in tamoxifen-treated mice compared to Cre- mice and Cre+ treated with vehicle alone. Further assessment of other immune cell infiltration including neutrophils, mast cells and T cells are ongoing.

Conclusion
Raf/MEK/ERK signalling, in the absence of tumour suppressor Merlin, significantly increases the infiltration of inflammatory cells such as macrophages into peripheral nerves even in the absence of injury. As this effect is enhanced in NF2 null mice, this suggests that Merlin plays an important role in inhibiting the inflammatory response in peripheral nerves. It also suggests that Merlin could be involved in maintaining the blood nerve barrier (BNB), as in its absence the greater influx of immune cells into the nerves and DRGs suggests a more complete loss of BNB function than just activation of the Raf/MEK/ERK cascade alone.
Clinical Features at Presentation for Glioblastoma Patients Impact Survival Predictions in a Machine Learning Model
Authors: Lawrence Alistair , Sinha Rohit , Mitrasinovic Stefan , Price Stephen 
Published: October 2021

Abstract

Aims
To generate an accurate prediction model for greater than median survival using Random Forest machine learning analysis and to compare the model to a traditional logistic regression analysis model on the same Glioblastoma Dataset.

Method
In this single centre retrospective cohort study, all patients with histologically diagnosed primary GB from October 2014 to April 2019 were included (n=466). Machine learning algorithms encompassing multiple logistic regression and a Random Forest, Gini index-based decision tree model with 100,000 trees were used. 17 clinical, molecular and treatment specific binarily categorised variables were used. The dataset was split 70:30 into training and validating sets.

Results
The dataset contained 466 patients. 326 patients made up the training set and 140 the validation set. The Random Forest model’s accuracy for predicting 18-month survival was 86.4% compared to the Logistic Regression model’s accuracy of 85.7%. The top 5 factors that the Random Forest model used to predict survival over 18 months were; mean MGMT status &gt;10%, if the patient underwent gross total resection, whether the patient had adjuvant temozolomide, whether the patient had a neurological deficit on presentation, and the sex of the patient.

Conclusion
Machine learning can be applied in the context of GB prognostic modelling. The models show that as well as the known factors that affect GB survival, the presenting symptom may also have an impact on prognostication.
Fatal Love
Authors: Devji Faisal 
Published: October 2021

Abstract
̧Interest is commonly seen as the fundamental unit of liberal politics—though in a narrowly economic sense it also forms the basis of a leftist vision of history. But while there has been no dearth of interest-based action as much as analysis in modern Indian politics, its “excessive” character, whether sacrificial, idealistic, or cruel, has permitted the category itself to be questioned, especially where religious relations are concerned. This chapter looks at how Ambedkar, Gandhi, Iqbal, Savarkar, and Jinnah were part of a conversation on the apparent “lack” or limitation of interest in Indian politics. For these men it was the absence of interest as a foundational category in Indian society, attributed to the fact that property did not define social relations there, that made for its violence as much as its spiritualism. Their problem was either to create interests where they didn’t exist, or to dispense with them altogether.
Development of Quality of Life Assessment Questionnaire Associated with Osmophobia in People with Migraine
Authors: Tanik Nermin , Bektas Murat 
Published: October 2021

AbstractBackgroundIt is important to implement disease-specific precautions to develop quality of life in migraine. The effect of osmophobia, which is one of the specific symptoms of migraine that might help to differentiate migraine from other headache disorders, on quality of life is unknown. The aim of the present study was to develop a practicable and reliable scale that assesses the effect of osmophobia on quality of life in migraine.MethodsThis cross-sectional study was carried out with 163 patients with migraine and 110 healthy individuals for control group. The scale items were constructed based on after literature review, expert opinions, and preliminary trial stage. A semi-structured interview was conducted with the patients by the Neurologist to evaluate the presence of osmophobia retrospectively. Migraine osmophobia-related quality of life assessment (MORA) consisted of 6 items including personal care, eating or cooking, house cleaning, close relationship, social life and traveling.ResultsThe Cronbach's α coefficient was 0.86; and the Guttman split-half coefficient was 0.83. Receiver operating characteristic analysis showed an area under the curve of 0.943 (95%) confidence interval [CI] = 0.902–0.984), a cutoff score of &gt;9.5, a sensitivity of 91.6%, a specificity of 85.7%. Mean scores of the MORA differed between people with migraine (with and without osmophobia) and healthy controls (&lt;0.001).ConclusionMORA is a valid and reliable self-report questionnaire that assesses the effect of osmophobia on quality of life in migraine. This questionnaire appears to be a practicable diagnostic instrument in clinical practice and research.
Ruminal in situ degradability of forage components and in vitro organic matter digestibility of warm-season grasses treated with calcium oxide
Authors: Ciriaco Francine M , Henry Darren D , Beierbach Romina , Schulmeister Tessa M , Ruiz-Moreno Martin , Garcia-Ascolani Mariana E , Podversich Federico , Dubeux Jose C B , DiLorenzo Nicolas 
Published: October 2021

Abstract
An experiment was designed to evaluate the effects of CaO on ruminal in situ degradability (RISD) of forage components and in vitro organic matter digestibility (IVOMD) of warm-season forages. Bahiagrass (Paspalum notatum; BH) or Tifton 85 bermudagrass (Cynodon spp.; BM) hay were stored in 20-L buckets in two consecutive years (n = 4/treatment) as follows: 1) untreated dry BH or BM (DH); 2) hydrated BH or BM stored for 7 d (W7); 3) hydrated BH or BM stored for 14 d (W14); 4) hydrated BH or BM + 5% [dry matter (DM) basis] CaO stored for 7 d (CO5-7); 5) hydrated BH or BM + 5% (DM basis) CaO stored for 14 d (CO5-14); and 6) hydrated BH or BM + 10% (DM basis) CaO stored for 14 d (CO10). With exception of the dry treatment (DH), tap water was added to forages under the remaining treatments to reach a DM concentration of 50%. Ruminal in situ degradability of DM, organic matter (OM), crude protein (CP), neutral detergent fiber (NDF), and acid detergent fiber (ADF) of BH and BM was determined for 24, 48, and 72 h in two ruminally cannulated steers consuming BH. Data were analyzed as a randomized block design using bucket as the experimental unit. The model included the fixed effect of treatment and the random effect of year. Concentration of NDF was reduced (P &lt; 0.001) when BH and BM were treated with 10% and 5% CaO and compared with DH. However, only CO10 promoted a reduction (P = 0.007) in ADF concentration of BH, whereas CO10 and CO5, regardless of storage length, reduced (P ≤ 0.006) ADF concentration of BM, when compared with DH. At all ruminal incubation time points, a treatment effect (P &lt; 0.001) was observed on RISD of DM, OM, CP, NDF, and ADF of BH and BM, where all treatments containing CaO promoted greater degradability when compared with DH, W7, and W14, which did not differ (P &gt; 0.05). Ruminal degradability of forage components was greatest (P &lt; 0.05) for CO10, followed by CO5-7 and CO5-14, which did not differ (P &gt; 0.05). In vitro organic matter digestibility was increased (P &lt; 0.001) in both BH and BM when CaO was applied and compared to DH. Treatment of BH and BM with CaO seems to be an effective method of promoting increased digestibility of forage components, including fiber fractions, when applied at 5% of the forage DM with potential additional benefits to BH when applied at 10%.
NEW METHOD FOR REDUCING ARTIFACTUAL FLOW DEFICITS CAUSED BY COMPENSATION TECHNIQUES IN THE CHORIOCAPILLARIS WITH OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY
Authors: Nesper Peter L. , Fawzi Amani A. 
Published: October 2021

Purpose:
To mitigate artifactual choriocapillaris flow deficits in optical coherence tomography angiography, which are a side effect of inverse structural optical coherence tomography compensation.

Methods:
In a modified algorithm, we set pixels in the original structural optical coherence tomography that were greater than one SD above the mean intensity (hyperreflective regions) to the mean pixel intensity of the image to remove hyporeflective regions in the inverse slab. We compared this algorithm to the original using flow deficit density and multiscale structural similarity index obtained from three distinct thresholding methods (local Phansalkar, global MinError (I), and global Li).

Results:
We included 16 eyes of 16 healthy subjects (31.1 ± 6.9 years, 10 females). Using the modified optical coherence tomography correction, flow deficit density was lower compared with the original algorithm using Phansalkar (P < 0.001) but higher using Li thresholding (P = 0.049). Multiscale structural similarity index was increased after applying the modified algorithm with all three thresholding methods (P < 0.001), indicating a closer relationship to the original optical coherence tomography angiography scan.

Conclusion:
We demonstrate a new method that significantly reduced the introduction of artifactual flow deficits in the choriocapillaris during postprocessing. Given the improved multiscale structural similarity index, we believe our algorithm more accurately represents the choriocapillaris.
Mechanically and Physiologically Optimizing Prosthetic Elevated Vacuum Systems in People with Transtibial Amputation: A Pilot Study
Authors: Youngblood Robert T. , Hafner Brian J. , Czerniecki Joseph M. , Larsen Brian G. , Allyn Katheryn J. , Sanders Joan E. 
Published: October 2021

ABSTRACT

Introduction
The most suitable elevated vacuum (EV) pressure may differ for each individual prosthesis user depending on suspension needs, socket fit, prosthetic components, and health. The mechanical and physiological effects of EV were evaluated in an effort to determine the optimal vacuum pressure for three individuals.

Methods
Instrumented EV sockets were created based on the participants’ regular EV sockets. Inductive distance sensors were embedded into the wall of the socket at select locations to measure limb movement relative to the socket. Each participant conducted an activity protocol while limb movement, limb fluid volume, and user-reported comfort were measured at various socket vacuum pressure settings.

Results
Increased socket vacuum pressure resulted in reduced limb-socket displacement for each participant; however, 81% to 93% of limb movement was eliminated by a vacuum pressure setting of 12 (approximately −9 inHg). Relative limb-socket displacement by sensor location varied for each participant, suggesting distinct differences related to socket fit or residual limb tissue content. The rate of limb fluid volume change and the change in socket comfort did not consistently differ with socket vacuum pressure, suggesting a more complex relationship unique to each individual.

Conclusions
Practitioners may use individual responses to optimize socket vacuum pressure settings, balancing the mechanical and physiological effects of EV for improved clinical outcomes.

Clinical Relevance
Understanding the effects of various socket vacuum pressure settings on individuals’ outcomes may improve clinical implementation of EV. In this study, the highest available vacuum setting did not always produce maximum comfort and limb fluid volume benefit, and similar levels of suspension were achieved with lower vacuum settings.
Splice correction therapies for familial hypercholesterolemic patients with low-density lipoprotein receptor mutations
Authors: McIntosh Craig S. , Watts Gerald F. , Wilton Steve D. , Aung-Htut May T. 
Published: October 2021

Purpose of review
Antisense oligomers (ASOs) have been available for decades: however, only recently have these molecules been applied clinically. This review aims to discuss the possible development of antisense-mediated splice correction therapies as precision medicines for familial hypercholesterolemic patients carrying mutations that compromise normal splicing of the low-density lipoprotein receptor (LDLR) gene transcript.

Recent findings
Three antisense drugs are currently being assessed in ongoing clinical trials for dyslipidemias, aiming to lower the plasma concentrations of lipoproteins that lead to end-organ damage, principally coronary artery disease. Although a handful of drugs may be applicable to many patients with familial hypercholesterolemia (FH), mutation-specific personalised antisense drugs may be even more effective in selected patients. Currently, there is no therapy that effectively addresses mutations in the LDLR, the major cause of FH. Many mutations in the LDLR that disrupt normal pre-mRNA processing could be applicable to splice correction therapy to restore receptor activity.

Summary
Precision medicine could provide long-term economic and social benefits if they can be implemented effectively and sustainably. Many mutations found in the LDLR gene could be amendable to therapeutic splice correction and we should consider developing a therapeutic ASO platform for these mutations.
Worldwide epidemiology of neuro-coronavirus disease in children: lessons for the next pandemic
Authors: Alcamo Alicia M. , McGuire Jennifer L. , Kanthimathinathan Hari Krishnan , Roa Juan David , Fink Ericka L. 
Published: October 2021

Purpose of review
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has overwhelmed the global community, negatively impacting patient health and research efforts; associated neurological manifestations are a significant cause of morbidity. This review outlines the worldwide epidemiology of neurologic manifestations of different SARS-CoV-2 clinical pediatric phenotypes, including acute coronavirus disease 2019 (COVID-19), multisystem inflammatory syndrome in children (MIS-C) and postacute sequelae of COVID-19 (PASC). We discuss strategies to develop adaptive global research platforms for future investigation into emerging pediatric neurologic conditions.

Recent findings
Multicenter, multinational studies show that neurological manifestations of acute COVID-19, such as smell/taste disorders, headache, and stroke, are common in hospitalized adults (82%) and children (22%), associated with increased mortality in adults. Neurological manifestations of MIS-C are reported in up to 20% of children, including headache, irritability, and encephalopathy. Data on PASC are emerging and include fatigue, cognitive changes, and headache. Reports of neurological manifestations in each phenotype are limited by lack of pediatric-informed case definitions, common data elements, and resources.

Summary
Coordinated, well resourced, multinational investigation into SARS-CoV-2-related neurological manifestations in children is critical to rapid identification of global and region-specific risk factors, and developing treatment and mitigation strategies for the current pandemic and future health neurologic emergencies.
The Effect of Lidocaine Delivered by Jet Injection on First Attempt Venous Access Success Rates in the Pediatric Emergency Department
Authors: Redmond Paul , Blackshear Chad , Davis Justin 
Published: October 2021

Background
Jet injection of 1% lidocaine (J-Tip) has been used in the pediatric emergency department (PED) to reduce pain associated with venipuncture, but there are limited data on the effect of J-Tip on first-attempt venous access success rates. We sought to determine if using a J-Tip altered the first-attempt venous access success rate in the PED. Then, we examined the effect of J-Tip use on pain scores and resource utilization during peripheral venous access.

Methods
We prospectively evaluated children over 6 months of age who required peripheral venous access in the PED. The exposure group received 0.25 mL of 1% buffered lidocaine via jet injection 90 seconds before peripheral venous access. The control group received no local anesthesia. Parent and nurse surveys were completed during the visit.

Results
There was no difference in first attempt success rate between the exposure (n = 136) and control (n = 90) groups (87% vs 88%, P = 0.82). J-Tip use was associated with improved pain scores based on child report (median 1 vs 3; P < 0.001), parent report (median 1 vs 3; P < 0.001), and nurse assessment (median 0 vs 3; P < 0.001).

Conclusions
Use of J-Tip in the PED to reduce pain associated with peripheral venous access did not lead to a reduction in first-attempt success rates for peripheral venous access. J-Tip was well received among nurses and parents and was associated with improved pain scores.
Guiding caregivers through disclosure: a qualitative investigation into caregivers’ responses to a disclosure intervention for HIV-infected children in Soweto, South Africa
Authors: Joyce Celeste , Ramsammy Candice , Galvin Lisa , Leshabane Given , Liberty Afaaf , Otwombe Kennedy , Buckley Janice , Milovanovic Minja , Violari Avy 
Published: October 2021

AbstractAwareness of Human Immunodeficiency Virus (HIV) status improves health outcomes in HIV infected children, yet disclosure is often delayed by hesitant caregivers. This qualitative investigation explored how 30 caregivers responded to a HIV Disclosure study conducted between 2017 and 2020 at Chris Hani Baragwanath Academic Hospital, Soweto, South Africa. Caregivers were assisted in disclosing to their children, aged 7-13 years; followed by a sub-sample of caregivers interviewed to elaborate on findings.1) Barriers to disclosure included caregivers being ill-equipped, fear of negative consequences and children considered lacking emotional or cognitive readiness. 2) Deflecting diagnosis and the need for medication motivated caregivers to disclosure. 3) Apprehension was evident during disclosure, however, overall disclosure was a positive experience with the support of the healthcare providers. These results highlight the significant role healthcare providers play in supporting caregivers through the disclosure process and how, in turn, this has a positive impact on the community as a whole.
Back to the medical classes-Part I-Strategy for return to the presential practices during COVID-19 pandemics in a Brazilian Medical School
Authors: Nogueira Saad Maria Auxiliadora , Jardim Pereira Vinicius César , Bueno Arnaldo Costa , Vieira Alan Araujo , Pombo March Maria de Fátima , Salgado Quintans Maria Dolores , Mendonça Barcellos Bruno , da Cunha Ferreira Laura , Moura Ronchini Karla Regina Oliveira , Coca Velarde Luis Guillermo , Araújo Cardoso Claudete Aparecida , da Silva André Ricardo Araujo 
Published: October 2021

AbstractIntroductionIn Brazil, practices of medical students have been interrupted due to COVID-19 to meet emergency demands.AimTo describe a strategy for a controlled return to the presential practices for medical students.MethodsWe developed a standardized protocol to be applied before and during the return of the practical classes in medical students of Universidade Federal Fluminense, in the follow months after COVID-19 pandemic beginning. The protocol was comprised in three parts: Remote training on COVID-19 prevention; Face-to-face training focused in COVID-19 prevention, handwashing and personal protective equipment use; Investigation of students COVID-19 status before starting practical activities and weekly monitoring for COVID-19 during seven weeks. The training was done by medical teachers in small groups for medical students of the last lective semester.ResultsThe classes were interrupted on March 12, 2020 and returned in August 10, 2020. Seventy-one students were trained and followed. The mean age was 26.6 years (26.7 ±0.835) and 54% were female. Forty-nine (69%) students over 71 had a private health insurance, 60 (84.5%) shared a house/apartment with one or more person and 12(16.9%) reported a previous comorbidity. Eighteen (25.4%) over 71 reported previous symptoms of COVID-19, being positive in two students. During the follow-up, fourteen (19.7%) over 71 students were placed in quarantine due to signals/symptoms compatible with COVID-19 or contact with symptomatic case. Only two cases (2.8%) were confirmed and occurred in Brazilian epidemiological week 37.ConclusionThe protocol was successful in minimizing COVID-19 acquisition during practical classes of medical students.