bluuebunny/crossref_metadata_2025_split huggingface dataset:
IMPACT OF A CLINICAL PATHWAY ON THE MANAGEMENT OF FIRST SEIZURES AT A DISTRICT GENERAL HOSPITAL
Authors: Georgieva Zoya , Altemimi Harith 
Published: October 2015

Diagnostic confidence and management of first seizures can be challenging, particularly for junior doctors. This audit evaluates the impact of a clinical pathway based on recommendations by the College of Emergency Medicine, which intended to improve the management of such patients at a UK DGH.A systematic search identified cases spanning 3 months either side of the date of introduction of the pathway. 23 pre- and 25 post-pathway cases presenting to A&E or as inpatients were randomly selected, excluding cases with a known seizure-related diagnosis.The pathway was only utilised in 16% of cases. Referral to neurology clinic increased from 30% to 52%, but attending within the recommended 2 weeks of ictus remained infrequent (8%). Clinical assessment worsened in several categories, including documenting a drug history, obtaining an ECG, and blood glucose measurement. Documenting discussions about driving decreased from 43% to 36%.Findings confirm suboptimal investigation and follow-up of first seizures, with a surprising deterioration after introduction of a local clinical guideline. This audit demonstrates the importance of cultural change in addition to the availability of a structured guideline. We propose this can be achieved by dedicated junior doctor training sessions and development of a patient information leaflet.
SERIAL NERVE CONDUCTION STUDIES IN A GUILLAIN-BARRÉ SYNDROME VARIANT: THE EVOLUTION OF DEMYELINATING CHANGES
Authors: Morgan Catherine , Wakerley Benjamin , Fuller Geraint 
Published: October 2015

Guillain Barré syndrome (GBS) varies both in terms of clinical phenotype and underlying pathology. Serial assessments allow greater understanding of the pathophysiology. The evolution of neurophysiological changes is particularly helpful in distinguishing between demyelination and reversible axonal conduction failure.Bilateral facial weakness with distal paraesthesias is a rare subtype of GBS. In the largest case series 64% had abnormalities in motor and 27% in sensory conduction on single neurophysiological assessments; this was interpreted as a demyelinating neuropathy.We report an 18-year-old male with bilateral lower motor neurone facial weakness preceded by distal paraesthesias following a ‘flu-like illness. Examination of power and sensation was normal. Deep tendon reflexes were present. Cerebrospinal fluid showed albuminocytologic dissociation. By 6 weeks his facial weakness had almost completely resolved without treatment.Serial nerve conduction studies were performed. The first study (day 4) found prolonged distal motor latency and delayed F waves in posterior tibial and common peroneal nerves; normal sensory studies. Second study (day 18) found distal motor latencies and F waves had increased in upper and lower limb nerves. Third study (day 60) found improvement but abnormalities remained with changes similar to the first study.The neurophysiological changes became more marked while he improved clinically. These serial studies confirmed the primary pathological process of this GBS variant to be demyelination.
A CLINICAL AUDIT OF ACUTE MANAGEMENT OF STROKE-LIKE EPISODES FROM A NATIONAL MITOCHONDRIAL DISEASE CENTRE
Authors: Shaw Sarah , Ng Yi Shiau , Whittaker Roger , McFarland Robert , Turnbull Doug , Gorman Grainne , Schaefer Andrew 
Published: October 2015

BackgroundMitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome is an acute and severe neurological presentation most commonly associated with a point mutation in the mitochondrial tRNA Leu (UUR)gene, m.3243A>G. The onset of stroke-like episodes (SLE) is often subtle and the diagnosis is not considered until progressive encephalopathy and refractory focal seizures ensue.ObjectiveTo review the acute management of SLE in patients with m.3243A>G related MELAS syndrome and implement revision of current centre guidelines.MethodThe medical records of adult patients (over 16 years) with m.3243A>G-related MELAS syndrome were reviewed over a 20 year period (1995 to 2014). Clinical presentation, brain imaging, EEG findings and seizure management were evaluated.ResultsWe identified 47 SLEs occurring in 22 m.3243A>G MELAS patients (mean age 33 years). Seizures of occipital origin were most common. Time to hospital admission and investigation was highly variable. Recognition and treatment of seizure activity was often delayed.ConclusionThis audit is the first to highlight the need for early recognition and prompt management of SLE in MELAS and the role of seizure control to improve clinical outcome.
CLINICAL MANIFESTATIONS OF DNMT1 MUTATIONS
Authors: Fox Robin , Gosal David , Ealing John , Murphy Helen 
Published: October 2015

DNMT1 gene mutations have been previously associated with neurological syndromes in small numbers of patients. We present seven cases – a patient with a previously unreported DNMT1 mutation and a family with six members affected by a more classical DNMT1 syndrome.A 20-year-old patient with a history of common variable immune deficiency presented with sensory loss. He developed a syndrome of hereditary sensory and autonomic neuropathy (HSAN1E), cataplexy, cerebellar atrophy, deafness, and cutaneous manifestations of a scleroderma spectrum disorder. There was no family history. Genetic testing revealed the patient was heterozygous for a previously unreported in-frame deletion mutation, c.1635_1637delCAA p.(Asn545del) in the DNMT1 gene exon 20. Parental DNA analysis suggested a de novo occurrence.A 53-year-old female patient presented with unsteadiness and falls. On assessment she was found to have cerebellar ataxia, bilateral ptosis, deafness and narcolepsy. Questioning revealed five further affected members of her family with the same clinical syndrome, in an autosomal dominant inheritance pattern. Genetic testing revealed a missense mutation in the exon 21 region of the DNMT1 gene – p.Ala570Val.DNMT1 mutations, whilst rare, are associated with a specific constellation of neurological features and increased recognition will lead to an increased understanding of this condition.
CASE REPORT: POURFOUR DU PETIT SYNDROME IN A PATIENT WITH MIGRAINE
Authors: Al-Ansari Aseel , Walters Richard Jon Llewellyn 
Published: October 2015

A 45-year old woman presented with a twelve-month history of intense migraines. She described episodes of blurred vision in association with the headaches, during which she invariably found that one or other of her pupils became dilated with a degree of eyelid retraction on the affected side. These unusual symptoms resolved spontaneously with improvement of the headache.After exclusion of a lesional cause with brain and neck imaging, we concluded that her symptoms were secondary to autonomic dysfunction in relation to her headache.Horner's syndrome is due to paralysis of the ipsilateral cervical sympathetic chain and comprises ptosis, miosis, enopthalmos and anhidrosis. A Reverse Horner's syndrome, otherwise known as Pourfour du Petit, in theory, is the opposite, and comprises eyelid retraction, mydriasis and hyperhidrosis. Where documented, it is attributed to irritation, rather than complete deficiency of the ipsilateral sympathetic chain. Previous case reports have shown that Pourfour du Petit can occur due to the same mechanisms as a Horner's syndrome. In only one other case report has it been described as an autonomic feature in relation to headache.
DELAYED DIAGNOSIS OF CADASIL IN A PATIENT WITH HEMIPLEGIC MIGRAINE
Authors: Matar Mazen , Sivagnanasundarum Jananee , Harikrishnan Sreedharan 
Published: October 2015

IntroductionCerebral Autosomal Dominant Angoipathy with Subcortical Infarcts and Leucoencephalopathy is a disorder caused by mutations in the NOTCH 3 gene. It is the most common cause of heritable stroke. Patients commonly present with migraine. Case report: we present a case of 31 year old female who came to neurology clinics with a history of recurrent attacks of migraine with aura of the hemiplegic type. These episodes began in her early twenties. She had no family history of note. Her examination was normal. Impression initially was felt to be migraine with aura.After agreeing to a treatment plan with the patient, she mentioned that her brother was also seen in Neurology clinics and that he was investigated with an MRI brain. His MRI images had shown wide spread white matter changes.We decided to perform an MRI brain which revealed subcortical and right anterior temporal white matter high signals. Genetic testing (NOTCH 3) confirmed diagnosis of CADASIL.Conclusionprevalence of CADASIL may be underestimated partly due to underdiagnoses, especially in patients presenting with migraine. Every attempt to gain an appropriate family history should be made to avoid misdiagnosis.
OCCIPITAL NERVE STIMULATION IN HIGHLY REFRACTORY CHRONIC HEADACHES: IDENTIFICATION OF POSSIBLE PREDICTORS OF SUCCESS
Authors: Miller Sarah , Fox Zoe , Watkins Laurence , Matharu Manjit 
Published: October 2015

IntroductionOccipital nerve stimulation (ONS) appears a promising treatment for refractory headaches. The procedure is invasive and response rates vary between studies. Identification of clinical predictors of outcome is therefore of importance.AimTo prospectively assess the efficacy of ONS in a cohort of intractable headache patients and identify clinical predictors of response.Methods165 patients undergoing ONS at a single centre were studied. Headache load was calculated at baseline and final follow-up. A positive response was defined as a 30% reduction in headache load. A multivariate logistic regression analysis was carried out to identify predictors of outcome.ResultsPatient group was highly refractory at baseline. At a mean follow up of 40 months the response rate of the group was 50%. Clinical factors identified with an increased likelihood of response were co-existent chronic migraine and chronic cluster and the presence of non-headache related pain disorders. Occipital pain was associated with a reduced likelihood of response. Adverse event rates were favourable.ConclusionONS is a potentially useful and safe treatment in refractory chronic headache disorders. The presence of multiple pain syndromes appears associated with increased likelihood of response and presence of occipital pain with a reduced likelihood.
PARKINSON'S DISEASE AND SPIRITUALITY
Authors: Coles Alasdair , Redfern Clare 
Published: October 2015

A limited literature suggests that people with Parkinson's disease have reduced religious beliefs, practices and experiences, compared to normal healthy controls. But we reasoned these results may be confounded by reduced mobility and social isolation associated with Parkinson's disease. So, we recruited a cohort of 42 Parkinson's patients and 39 controls with chronic respiratory disease, non-neurological autoimmune disease or rheumatological problems. Each subject was examined twice, 12 months apart and assessed on validated scales of handicap and impairment, with spirituality measured by the modified Brief Multidimensional Measure of Religiousness/Spirituality (BMMRS), an abbreviated Hood Mysticism Scale, and the Cloninger Transcendance Inventory.As expected, the Parkinson's group showed a greater decline in mobility and cognitive function over 12 months, compared to controls yet their religiosity scores were undiminished. Quantitative analysis showed significantly increased positive spiritual experiences in the Parkinson's group (p=0.04) relative to controls. “Religious support”, a proxy for involvement in a religious community, was maintained despite decreasing mobility. Qualitative accounts indicated that faith and spirituality were maintained in those patients with PD for whom it was important at baseline. We identified no aspect of faith that was reduced by degeneration of basal ganglia pathways.
Breast Cancer Risk in Relation to Ambient Air Pollution Exposure at Residences in the Sister Study Cohort
Authors: Reding Kerryn W. , Young Michael T. , Szpiro Adam A. , Han Claire J. , DeRoo Lisa A. , Weinberg Clarice , Kaufman Joel D. , Sandler Dale P. 
Published: October 2015

Abstract
Background: Some but not all past studies reported associations between components of air pollution and breast cancer, namely fine particulate matter ≤2.5 μm (PM2.5) and nitrogen dioxide (NO2). It is yet unclear whether risks differ according to estrogen receptor (ER) and progesterone receptor (PR) status.
Methods: This analysis includes 47,591 women from the Sister Study cohort enrolled from August 2003 to July 2009, in whom 1,749 invasive breast cancer cases arose from enrollment to January 2013. Using Cox proportional hazards and polytomous logistic regression, we estimated breast cancer risk associated with residential exposure to NO2, PM2.5, and PM10.
Results: Although breast cancer risk overall was not associated with PM2.5 [HR = 1.03; 95% confidence intervals (CI), 0.96–1.11], PM10 (HR = 0.99; 95% CI, 0.98–1.00), or NO2 (HR = 1.02; 95% CI, 0.97–1.07), the association with NO2 differed according to ER/PR subtype (P = 0.04). For an interquartile range (IQR) difference of 5.8 parts per billion (ppb) in NO2, the relative risk (RR) of ER+/PR+ breast cancer was 1.10 (95% CI, 1.02–1.19), while there was no evidence of association with ER−/PR− (RR = 0.92; 95% CI, 0.77–1.09; Pinteraction = 0.04).
Conclusions: Within the Sister Study cohort, we found no significant associations between air pollution and breast cancer risk overall. But we observed an increased risk of ER+/PR+ breast cancer associated with NO2.
Impact: Though these results suggest there is no substantial increased risk for breast cancer overall in relation to air pollution, NO2, a marker of traffic-related air pollution, may differentially affect ER+/PR+ breast cancer. Cancer Epidemiol Biomarkers Prev; 24(12); 1907–9. ©2015 AACR.
New Strategies in Engineering T-cell Receptor Gene-Modified T cells to More Effectively Target Malignancies
Authors: Schmitt Thomas M. , Stromnes Ingunn M. , Chapuis Aude G. , Greenberg Philip D. 
Published: October 2015

Abstract
The immune system, T cells in particular, have the ability to target and destroy malignant cells. However, antitumor immune responses induced from the endogenous T-cell repertoire are often insufficient for the eradication of established tumors, as illustrated by the failure of cancer vaccination strategies or checkpoint blockade for most tumors. Genetic modification of T cells to express a defined T-cell receptor (TCR) can provide the means to rapidly generate large numbers of tumor-reactive T cells capable of targeting tumor cells in vivo. However, cell-intrinsic factors as well as immunosuppressive factors in the tumor microenvironment can limit the function of such gene-modified T cells. New strategies currently being developed are refining and enhancing this approach, resulting in cellular therapies that more effectively target tumors and that are less susceptible to tumor immune evasion. Clin Cancer Res; 21(23); 5191–7. ©2015 AACR.
Multimodal Image-Guided Surgical and Photodynamic Interventions in Head and Neck Cancer: From Primary Tumor to Metastatic Drainage
Authors: Muhanna Nidal , Cui Liyang , Chan Harley , Burgess Laura , Jin Cheng S. , MacDonald Thomas D. , Huynh Elizabeth , Wang Fan , Chen Juan , Irish Jonathan C. , Zheng Gang 
Published: October 2015

Abstract
Purpose: The low survival rate of head and neck cancer (HNC) patients is attributable to late disease diagnosis and high recurrence rate. Current HNC staging has inadequate accuracy and low sensitivity for effective diagnosis and treatment management. The multimodal porphyrin lipoprotein-mimicking nanoparticle (PLP), intrinsically capable of positron emission tomography (PET), fluorescence imaging, and photodynamic therapy (PDT), shows great potential to enhance the accuracy of HNC staging and potentially HNC management.
Experimental Design: Using a clinically relevant VX-2 buccal carcinoma rabbit model that is able to consistently develop metastasis to regional lymph nodes after tumor induction, we investigated the abilities of PLP for HNC diagnosis and management.
Results: PLPs facilitated accurate detection of primary tumor and metastatic nodes (their PET image signal to surrounding muscle ratios were 10.0 and 7.3, respectively), and provided visualization of the lymphatic drainage from tumor to regional lymph nodes by both preoperative PET and intraoperative fluorescence imaging, allowing the identification of unknown primaries and recurrent tumors. PLP-PDT significantly enhanced cell apoptosis in mouse tumors (73.2% of PLP-PDT group vs 7.1% of PLP alone group) and demonstrated complete eradication of primary tumors and obstruction of tumor metastasis in HNC rabbit model without toxicity in normal tissues or damage to adjacent critical structures.
Conclusions: PLPs provide a multimodal imaging and therapy platform that could enhance HNC diagnosis by integrating PET/computed tomography and fluorescence imaging, and improve HNC therapeutic efficacy and specificity by tailoring treatment via fluorescence-guided surgery and PDT. Clin Cancer Res; 22(4); 961–70. ©2015 AACR.
Increased Expression of Beige/Brown Adipose Markers from Host and Breast Cancer Cells Influence Xenograft Formation in Mice
Authors: Singh Rajan , Parveen Meher , Basgen John M. , Fazel Sayeda , Meshesha Meron F. , Thames Easter C. , Moore Brandis , Martinez Luis , Howard Carolyn B. , Vergnes Laurent , Reue Karen , Pervin Shehla 
Published: October 2015

Abstract
The initiation and progression of breast cancer is a complex process that is influenced by heterogeneous cell populations within the tumor microenvironment. Although adipocytes have been shown to promote breast cancer development, adipocyte characteristics involved in this process remain poorly understood. In this study, we demonstrate enrichment of beige/brown adipose markers, contributed from the host as well as tumor cells, in the xenografts from breast cancer cell lines. In addition to uncoupling protein-1 (UCP1) that is exclusively expressed in beige/brown adipocytes, gene expression for classical brown (MYF5, EVA1, and OPLAH) as well as beige (CD137/TNFRSF9 and TBX1) adipocyte markers was also elevated in the xenografts. Enrichment of beige/brown characteristics in the xenografts was independent of the site of implantation of the breast tumor cells. Early stages of xenografts showed an expansion of a subset of mammary cancer stem cells that expressed PRDM16, a master regulator of brown adipocyte differentiation. Depletion of UCP1+ or Myf5+ cells significantly reduced tumor development. There was increased COX2 (MT-CO2) expression, which is known to stimulate formation of beige adipocytes in early xenografts and treatment with a COX2 inhibitor (SC236) reduced tumor growth. In contrast, treatment with factors that induce brown adipocyte differentiation in vitro led to larger tumors in vivo. A panel of xenografts derived from established breast tumor cells as well as patient tumor tissues were generated that expressed key brown adipose tissue–related markers and contained cells that morphologically resembled brown adipocytes.
Implications: This is the first report demonstrating that beige/brown adipocyte characteristics could play an important role in breast tumor development and suggest a potential target for therapeutic drug design. Mol Cancer Res; 14(1); 78–92. ©2015 AACR.
Risk Prediction Models for Colorectal Cancer: A Systematic Review
Authors: Usher-Smith Juliet A. , Walter Fiona M. , Emery Jon D. , Win Aung K. , Griffin Simon J. 
Published: October 2015

AbstractColorectal cancer is the second leading cause of cancer-related death in Europe and the United States. Survival is strongly related to stage at diagnosis and population-based screening reduces colorectal cancer incidence and mortality. Stratifying the population by risk offers the potential to improve the efficiency of screening. In this systematic review we searched Medline, EMBASE, and the Cochrane Library for primary research studies reporting or validating models to predict future risk of primary colorectal cancer for asymptomatic individuals. A total of 12,808 papers were identified from the literature search and nine through citation searching. Fifty-two risk models were included. Where reported (n = 37), half the models had acceptable-to-good discrimination (the area under the receiver operating characteristic curve, AUROC &gt;0.7) in the derivation sample. Calibration was less commonly assessed (n = 21), but overall acceptable. In external validation studies, 10 models showed acceptable discrimination (AUROC 0.71–0.78). These include two with only three variables (age, gender, and BMI; age, gender, and family history of colorectal cancer). A small number of prediction models developed from case–control studies of genetic biomarkers also show some promise but require further external validation using population-based samples. Further research should focus on the feasibility and impact of incorporating such models into stratified screening programmes. Cancer Prev Res; 9(1); 13–26. ©2015 AACR.See related article by Frank L. Meyskens, Jr., p. 11
Effect of Hyperacute Administration (Within 6 Hours) of Transdermal Glyceryl Trinitrate, a Nitric Oxide Donor, on Outcome After Stroke
Authors: Woodhouse Lisa , Scutt Polly , Krishnan Kailash , Berge Eivind , Gommans John , Ntaios George , Wardlaw Joanna , Sprigg Nikola , Bath Philip M. 
Published: October 2015

Background and Purpose—
Nitric oxide donors are candidate treatments for acute stroke, potentially through hemodynamic, reperfusion, and neuroprotectant effects, especially if given early. Although the large Efficacy of Nitric Oxide in Stroke (ENOS) trial of transdermal glyceryl trinitrate (GTN) was neutral, a prespecified subgroup suggested that GTN improved functional outcome if administered early after stroke onset.

Methods—
Prospective analysis of subgroup of patients randomized into the ENOS trial within 6 hours of stroke onset. Safety and efficacy of GTN versus no GTN were assessed using data on early and late outcomes.

Results—

Two hundred seventy-three patients were randomized within 6 hours of ictus: mean (SD) age, 69.9 (12.7) years; men, 154 (56.4%); ischemic stroke, 208 (76.2%); Scandinavian Stroke Scale, 32.1 (11.9); and total anterior circulation syndrome, 86 (31.5%). When compared with no GTN, the first dose of GTN lowered blood pressure by 9.4/3.3 mm Hg (
P
<0.01,
P
=0.064) and shifted the modified Rankin Scale to a better outcome by day 90, adjusted common odds ratio, 0.51 (95% confidence interval, 0.32–0.80). Significant beneficial effects were also seen with GTN for disability (Barthel Index), quality of life (EuroQol-Visual Analogue Scale), cognition (telephone Mini-Mental State Examination), and mood (Zung Depression Scale). GTN was safe to administer with less serious adverse events by day 90 (GTN 18.8% versus no GTN 34.1%) and death (hazard ratio, 0.44; 95% confidence interval, 0.20–0.99;
P
=0.047).

Conclusions—
In a subgroup analysis of the large ENOS trial, transdermal GTN was safe to administer and associated with improved functional outcome and fewer deaths when administered within 6 hours of stroke onset.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00989716.