bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diet, exercise and dementia: The potential impact of a Mediterranean diet pattern and physical activity on cognitive health in a UK population
Authors: Bundy R. , Minihane A. M. 
Published: August 2018

AbstractDiet and physical activity play key roles in maintaining health and preventing or delaying disease. The global prevalence of dementia, an umbrella term describing a set of symptoms which affect cognitive function, is set to rise dramatically by 2050, with current drug treatments inadequate. Diet and physical activity are modifiable factors in dementia, influencing both disease risk and pathophysiology. It has been known since the 1950s that a Mediterranean diet has positive health benefits. Over the past 25 years, a causal link has been shown between consumption of a Mediterranean diet and decreased risk of cardiovascular disease, particularly in Mediterranean countries. There have also been indications that a Mediterranean diet and increased physical activity can improve cognitive health and delay the onset of dementia. However, causative demonstrations of these effects, as well as the feasibility of implementing such lifestyle changes in a non‐Mediterranean population, are lacking. The new MedEx‐UK programme will attempt to address both these points.
Sm‐p80‐based schistosomiasis vaccine: double‐blind preclinical trial in baboons demonstrates comprehensive prophylactic and parasite transmission‐blocking efficacy
Authors: Zhang Weidong , Molehin Adebayo J. , Rojo Juan U. , Sudduth Justin , Ganapathy Pramodh K. , Kim Eunjee , Siddiqui Arif J. , Freeborn Jasmin , Sennoune Souad R. , May Jordan , Lazarus Samra , Nguyen Catherine , Redman Whitni K. , Ahmad Gul , Torben Workineh , Karmakar Souvik , Le Loc , Kottapalli Kameswara R. , Kottapalli Pratibha , Wolf Roman F. , Papin James F. , Carey David , Gray Sean A. , Bergthold Jenn D. , Damian Raymond T. , Mayer Bryan T. , Marks Florian , Reed Steven G. , Carter Darrick , Siddiqui Afzal A. 
Published: August 2018

AbstractSchistosomiasis is of public health importance to an estimated one billion people in 79 countries. A vaccine is urgently needed. Here, we report the results of four independent, double‐blind studies of an Sm‐p80‐based vaccine in baboons. The vaccine exhibited potent prophylactic efficacy against transmission of Schistosoma mansoni infection and was associated with significantly less egg‐induced pathology, compared with unvaccinated control animals. Specifically, the vaccine resulted in a 93.45% reduction of pathology‐producing female worms and significantly resolved the major clinical manifestations of hepatic/intestinal schistosomiasis by reducing the tissue egg‐load by 89.95%. A 35‐fold decrease in fecal egg excretion in vaccinated animals, combined with an 81.51% reduction in hatching of eggs into the snail‐infective stage (miracidia), demonstrates the parasite transmission‐blocking potential of the vaccine. Substantially higher Sm‐p80 expression in female worms and Sm‐p80‐specific antibodies in vaccinated baboons appear to play an important role in vaccine‐mediated protection. Preliminary analyses of RNA sequencing revealed distinct molecular signatures of vaccine‐induced effects in baboon immune effector cells. This study provides comprehensive evidence for the effectiveness of an Sm‐p80‐based vaccine for schistosomiasis.
Reducing saccadic artifacts and confounds in brain imaging studies through experimental design
Authors: Tal Noam , Yuval‐Greenberg Shlomit 
Published: August 2018

AbstractSaccades constitute a major source of artifacts and confounds in brain imaging studies. Whereas some artifacts can be removed by omitting segments of data, saccadic artifacts cannot be typically eliminated by this method because of their high occurrence rate even during fixation (1–3 per second). Some saccadic artifacts can be alleviated by offline‐correction algorithms, but these methods leave nonnegligible residuals and cannot mitigate the saccade‐related visual activity. Here, we propose a novel yet simple approach for diminishing saccadic artifacts and confounds through experimental design. We suggest that specific tasks can lead to substantially less saccade occurrences around the time of stimulus presentation, starting from slightly before its onset and lasting for a few hundred milliseconds. In three experiments, we compared the frequency and size of saccades in a variety of tasks. Results of Experiment 1 showed that a foveal change‐detection task reduced the number and sizes of saccades, relative to a parafoveal orientation‐discrimination task. Experiment 2 replicated this finding with a parafoveal object recognition task. Experiment 3 showed that both foveal and parafoveal continuous change detection tasks induced fewer and smaller saccades than a discrete orientation‐discrimination task. We conclude that adding a foveal or a parafoveal continuous task reduces saccades' number and size. This would lead to better artifact correction and enable the omission of contaminated data segments. This study may be the first step toward developing saccade‐free experimental designs.
Rural Landowners, Energy Leasing, and Patterns of Risk and Inequality in the Shale Gas Industry
Authors: Bugden Dylan , Stedman Richard 
Published: August 2018

AbstractLandowners who lease property for shale gas development (i.e., “fracking”) face the possibility of procedural disenfranchisement and risk. They also stand to benefit financially from bonus and royalty payments. This article evaluates the frequency with which these experiences occur and how they vary between landowners. Using a mixed‐methods approach, we combine surveys and interviews with northeastern Pennsylvania landowners with a content analysis of energy lease documents. We find that landowners generally experience relatively infrequent environmental harm, receive substantial financial benefits, and leverage their property rights to secure better lease conditions. However, our findings also demonstrate that procedural disenfranchisement does occur, environmental risks are infrequent but real, and outcomes tend to vary by firm‐specific rather than sociostructural factors. Accordingly, the advantages conferred by private property are not a panacea for the alleviation of risk and inequality in energy development. These findings inject considerable nuance into ongoing discussions of risk, inequality, and shale gas development: Rather than perceiving themselves as victims, landowners tend to see themselves as beneficiaries of industry activity, an experience structured directly by their ownership of property and mineral rights.
Retrospective analysis of ocular neuropathies in diabetic dogs following cataract surgery
Authors: Foote Braidee C. , Michau Tammy M. , Welihozkiy Anja , Stine Jessica M. 
Published: August 2018

AbstractObjectivesTo describe and compare the cumulative incidence and clinical progression of ocular neuropathies in diabetic dogs vs nondiabetic dogs following cataract surgery.MethodsMedical records of 196 diabetic and 442 nondiabetic dogs who underwent cataract surgery between 2004 and 2015 were reviewed. The percentage of patients affected by neuropathy and potential risk factors were compared between groups.ResultsPatients with diabetes mellitus (DM) were 20.4 times more likely to develop an ocular neuropathy than patients withoutDM(12.24% vs 0.68%). Twenty‐four diabetic patients were affected by mononeuropathies or polyneuropathies including Horner's syndrome (n = 20), facial neuropathy (n = 5), and neurogenic keratoconjunctivitis sicca (NKCS) (n = 5). The odds of a diabetic patient developing Horner's syndrome andNKCSwere 86.3 and 20.7 times higher than a nondiabetic patient, respectively. The average duration ofDMprior to diagnosis of neuropathy was 659 days (range 110‐2390 days; median 559 days). Complete resolution was achieved in 10 of 22 neuropathies (45%) within an average of 248 days (range 21‐638 days; median 187 days) after diagnosis.ConclusionsThe odds of developing an ocular neuropathy, specifically Horner's syndrome andNKCS, are statistically higher in diabetic patients compared to nondiabetic patients. Neuropathies were observed as a long‐term complication in this group of diabetic patients, and complete resolution of the neuropathy was observed in less than half of the affected population.
Microbiota of the conjunctival sac of 120 healthy cats
Authors: Büttner Jessica Nina , Schneider Marianne , Csokai Jaqueline , Müller Elisabeth , Eule Johanna Corinna 
Published: August 2018

AbstractObjectivesTo describe the bacterial and fungal microbiota of the conjunctiva and factors influencing these microbiota of healthy cats. To evaluate the antimicrobial resistance profile and discuss the use of appropriate antimicrobial drugs.Animals studiedOne hundred and twenty healthy catsProceduresConjunctival samples with dry or premoistened swabs were obtained from both eyes and cultured for aerobic and anaerobic bacteria and fungi. In vitro bacterial, susceptibility testing was performed. The effects of age, sex, breed, season, living environment, and sample collection technique on the frequency and composition of microbial isolation were evaluated.ResultsIn 49 of 120 cats (40.8%) and 73 of 240 swabs (30.4%), microorganisms were isolated. Of the isolates, 71% (61/86) were Gram‐positive bacteria, 26% (22/86) were Gram‐negative bacteria, and 3% (3/86) were fungi.Staphylococcus felis(17/86; 19.8%) was the most commonly isolated species.Moraxella osloensis(5/86; 5.8%) was the most frequent Gram‐negative species. The season had a statistically significant influence (P = 0.04) on the frequency of isolation. The use of premoistened swabs increased the rate of Gram‐positive bacterial detection significantly (P = 0.03). The in vitro susceptibility testing showed high efficacy of chloramphenicol, gentamicin, pradofloxacin, and enrofloxacin.ConclusionsThe isolated microbiota aligns with previous studies performed in other countries, although the microbiota of cats in the present study showed wider bacterial diversity, and more Gram‐negative species were isolated. Swab sampling should be performed with premoistened swabs. The topical antimicrobials gentamicin and chloramphenicol are suitable therapeutics for first‐line treatment.
Ventral stabilization of thoracic kyphosis through bilateral intercostal thoracotomies using SOP (String of Pearls) plates contoured after a 3‐dimensional print of the spine
Authors: Mathiesen Christina B. , de la Puerta Benito , Groth Anna M. , Rutherford Scott , Cappello Rodolfo 
Published: August 2018

AbstractObjectiveTo describe a novel vertebral body stabilization and report its outcome in dogs with thoracic kyphosis and secondary myelopathy.Study designCase series.AnimalsSix pugs with thoracic kyphosis and secondary myelopathy.MethodsMedical records (2012‐2017) of dogs with chronic progressive pelvic limb ataxia and ambulatory proprioceptive paraparesis due to thoracic kyphosis were reviewed. Dogs were evaluated via MRI and computed tomography. A 3‐dimensional print of the kyphotic vertebral segment was used to precontour the SOP (String of Pearls) plates. Bilateral double, dorsal intercostal thoracotomies were performed to place precontoured SOP on the vertebral bodies. Long‐term (6‐16 months) clinical outcome was determined on the basis of neurological scoring (NS) and owner questionnaire.ResultsThe only intraoperative complication consisted of a lung laceration due to preexisting adhesions. Postoperative complications included seroma formation (n = 2) and incidental radiographic evidence of screw breakage (n = 2). NS at presentation ranged between 2 and 4 and improved to 1 at long‐term follow‐up in all dogs but 1 (NS = 2). All owners felt that their dog had excellent quality of life at follow‐up.ConclusionIn spite of the challenging local anatomy, all dogs undergoing vertebral stabilization with SOP placement experienced a good clinical outcome.Clinical significanceStabilization of vertebral bodies with precontoured SOP placed through bilateral thoracotomies may be considered as a treatment option for dogs with thoracic kyphosis and secondary myelopathy.
Fatigue‐related group III/IV muscle afferent feedback facilitates intracortical inhibition during locomotor exercise
Authors: Sidhu Simranjit K. , Weavil Joshua C. , Thurston Taylor S. , Rosenberger Dorothea , Jessop Jacob E. , Wang Eivind , Richardson Russell S. , McNeil Chris J. , Amann Markus 
Published: August 2018

Key Points
This study investigated the influence of group III/IV muscle afferents on corticospinal excitability during cycling exercise and focused on GABAB neuron‐mediated inhibition as a potential underlying mechanism.
The study provides novel evidence to demonstrate that group III/IV muscle afferent feedback facilitates inhibitory intracortical neurons during whole body exercise.
Firing of these interneurons probably contributes to the development of central fatigue during physical activity.
AbstractWe investigated the influence of group III/IV muscle afferents in determining corticospinal excitability during cycling exercise and focused on GABAB neuron‐mediated inhibition as a potential underlying mechanism. Both under control conditions (CTRL) and with lumbar intrathecal fentanyl (FENT) impairing feedback from group III/IV leg muscle afferents, subjects (n = 11) cycled at a comparable vastus‐lateralis EMG signal (∼0.26 mV) before (PRE; 100 W) and immediately after (POST; 90 ± 2 W) fatiguing constant‐load cycling exercise (80% Wpeak; 221 ± 10 W; ∼8 min). During, PRE and POST cycling, single and paired‐pulse (100 ms interstimulus interval) transcranial magnetic stimulations (TMS) were applied to elicit unconditioned and conditioned motor‐evoked potentials (MEPs), respectively. To distinguish between cortical and spinal contributions to the MEPs, cervicomedullary stimulations (CMS) were used to elicit unconditioned (CMS only) and conditioned (TMS+CMS, 100 ms interval) cervicomedullary motor‐evoked potentials (CMEPs). While unconditioned MEPs were unchanged from PRE to POST in CTRL, unconditioned CMEPs increased significantly, resulting in a decrease in unconditioned MEP/CMEP (P < 0.05). This paralleled a reduction in conditioned MEP (P < 0.05) and no change in conditioned CMEP. During FENT, unconditioned and conditioned MEPs and CMEPs were similar and comparable during PRE and POST (P > 0.2). These findings reveal that feedback from group III/IV muscle afferents innervating locomotor muscle decreases the excitability of the motor cortex during fatiguing cycling exercise. This impairment is, at least in part, determined by the facilitating effect of these sensory neurons on inhibitory GABAB intracortical interneurons.
Drooling Reduction Intervention randomised trial (DRI): comparing the efficacy and acceptability of hyoscine patches and glycopyrronium liquid on drooling in children with neurodisability
Authors: Parr Jeremy R , Todhunter Emma , Pennington Lindsay , Stocken Deborah , Cadwgan Jill , O’Hare Anne E , Tuffrey Catherine , Williams Jane , Cole Mike , Colver Allan F 
Published: August 2018

ObjectiveInvestigate whether hyoscine patch or glycopyrronium liquid is more effective and acceptable to treat drooling in children with neurodisability.DesignMulticentre, single-blind, randomised controlled trial.SettingRecruitment through neurodisability teams; treatment by parents.ParticipantsNinety children with neurodisability who had never received medication for drooling (55 boys, 35 girls; median age 4 years). Exclusion criteria: medication contraindicated; in a trial that could affect drooling or management.InterventionChildren were randomised to receive a hyoscine skin patch or glycopyrronium liquid. Dose was increased over 4 weeks to achieve optimum symptom control with minimal side-effects; steady dose then continued to 12 weeks.Primary and secondary outcomesPrimary outcome: Drooling Impact Scale (DIS) score at week-4. Secondary outcomes: change in DIS scores over 12 weeks, Drooling Severity and Frequency Scale and Treatment Satisfaction Questionnaire for Medication; adverse events; children’s perception about treatment.ResultsBoth medications yielded clinically and statistically significant reductions in mean DIS at week-4 (25.0 (SD 22.2) for hyoscine and 26.6 (SD 16) for glycopyrronium). There was no significant difference in change in DIS scores between treatment groups. By week-12, 26/47 (55%) children starting treatment were receiving hyoscine compared with 31/38 (82%) on glycopyrronium. There was a 42% increased chance of being on treatment at week-12 for children randomised to glycopyrronium relative to hyoscine (1.42, 95% CI 1.04 to 1.95).ConclusionsHyoscine and glycopyrronium are clinically effective in treating drooling in children with neurodisability. Hyoscine produced more problematic side effects leading to a greater chance of treatment cessation.Trial registration numbersISRCTN75287237; EUDRACT: 2013-000863-94; Medicines and Healthcare Products Regulatory Agency: 17136/0264/001-0003
A Phase I Trial of a Guadecitabine (SGI-110) and Irinotecan in Metastatic Colorectal Cancer Patients Previously Exposed to Irinotecan
Authors: Lee Valerie , Wang Judy , Zahurak Marianna , Gootjes Elske , Verheul Henk M. , Parkinson Rose , Kerner Zachary , Sharma Anup , Rosner Gary , De Jesus-Acosta Ana , Laheru Daniel , Le Dung T. , Oganesian Aram , Lilly Ellen , Brown Thomas , Jones Peter , Baylin Stephen , Ahuja Nita , Azad Nilofer 
Published: August 2018

AbstractPurpose:Chemotherapeutic resistance eventually develops in all patients with metastatic colorectal cancer (mCRC). Gene silencing through promoter demethylation is one potential reversible mechanism of resistance with administration of hypomethylating agents. We evaluated the safety and tolerability of guadecitabine and irinotecan in patients with mCRC previously treated with irinotecan.Patients and Methods:In this 3+3 dose-escalation study, patients with mCRC previously exposed to irinotecan received guadecitabine days 1 to 5 of a 28-day cycle and irinotecan 125 mg/m2 days 8 and 15 [dose level (DL) 1, guadecitabine 45 mg/m2; DL −1: guadecitabine 30 mg/m2; DL −1G: guadecitabine 30 mg/m2 with growth factor support (GFS); DL 1G: guadecitabine 45 mg/m2 with GFS].Results:Twenty-two patients were treated across four DLs. Dose-limiting toxicities were neutropenic fever (DL 1 and −1G), biliary drain infection (DL −1), colonic obstruction (DL −1), and severe dehydration (DL 1G). Most common toxicities were neutropenia (82% any grade, 77% Grade 3/4), neutropenic fever (23%), leukopenia (73% any grade, 50% Grade 3/4), and injection site reactions (64% total, 0% Grade 3/4). Patients received a median of 4.5 cycles of treatment; 12/17 evaluable patients had stable disease as best response, with one having initial disease progression but subsequently durable partial response. Circulating tumor DNA showed decrease in global demethylation by LINE-1 after treatment.Conclusions:We report the first study of chemo-priming with epigenetic therapy in gastrointestinal cancers. Guadecitabine 45 mg/m2 and irinotecan 125 mg/m2 with GFS was safe and tolerable in patients with mCRC, with early indication of benefit. These data have provided the basis for an ongoing phase II randomized, multicenter trial.
iRGD-guided Tumor-penetrating Nanocomplexes for Therapeutic siRNA Delivery to Pancreatic Cancer
Authors: Lo Justin H. , Hao Liangliang , Muzumdar Mandar D. , Raghavan Srivatsan , Kwon Ester J. , Pulver Emilia M. , Hsu Felicia , Aguirre Andrew J. , Wolpin Brian M. , Fuchs Charles S. , Hahn William C. , Jacks Tyler , Bhatia Sangeeta N. 
Published: August 2018

Abstract
Pancreatic cancer is one of the leading causes of cancer-related death, with 5-year survival of 8.5%. The lack of significant progress in improving therapy reflects our inability to overcome the desmoplastic stromal barrier in pancreatic ductal adenocarcinoma (PDAC) as well as a paucity of new approaches targeting its genetic underpinnings. RNA interference holds promise in targeting key mutations driving PDAC; however, a nucleic acid delivery vehicle that homes to PDAC and breaches the stroma does not yet exist. Noting that the cyclic peptide iRGD mediates tumor targeting and penetration through interactions with αvβ3/5 integrins and neuropilin-1, we hypothesized that “tandem” peptides combining a cell-penetrating peptide and iRGD can encapsulate siRNA to form tumor-penetrating nanocomplexes (TPN) capable of delivering siRNA to PDAC. The use of directly conjugated iRGD is justified by receptor expression patterns in human PDAC biopsies. In this work, we optimize iRGD TPNs with polyethylene glycol (PEG)-peptide conjugates for systemic delivery to sites of disease. We show that TPNs effectively knockdown siRNA targets in PDAC cell lines and in an immunocompetent genetically engineered mouse model of PDAC. Furthermore, we validate their tumor-penetrating ability in three-dimensional organoids and autochthonous tumors. In murine therapeutic trials, TPNs delivering anti-Kras siRNA significantly delay tumor growth. Thus, iRGD TPNs hold promise in treating PDAC by not only overcoming physical barriers to therapy, but by leveraging the stroma to achieve knockdown of the gold-standard genetic target. Moreover, the modular construction of this delivery platform allows for facile adaptation to future genetic target candidates in pancreatic cancer. Mol Cancer Ther; 17(11); 2377–88. ©2018 AACR.
Improving Efficacy and Safety of Agonistic Anti-CD40 Antibody Through Extracellular Matrix Affinity
Authors: Ishihara Jun , Ishihara Ako , Potin Lambert , Hosseinchi Peyman , Fukunaga Kazuto , Damo Martina , Gajewski Thomas F. , Swartz Melody A. , Hubbell Jeffrey A. 
Published: August 2018

Abstract
CD40 is an immune costimulatory receptor expressed by antigen-presenting cells. Agonistic anti-CD40 antibodies have demonstrated considerable antitumor effects yet can also elicit serious treatment-related adverse events, such as liver toxicity, including in man. We engineered a variant that binds extracellular matrix through a super-affinity peptide derived from placenta growth factor-2 (PlGF-2123-144) to enhance anti-CD40′s effects when administered locally. Peritumoral injection of PlGF-2123-144-anti-CD40 antibody showed prolonged tissue retention at the injection site and substantially decreased systemic exposure, resulting in decreased liver toxicity. In four mouse tumor models, PlGF-2123-144-anti-CD40 antibody demonstrated enhanced antitumor efficacy compared with its unmodified form and correlated with activated dendritic cells, B cells, and T cells in the tumor and in the tumor-draining lymph node. Moreover, in a genetically engineered BrafV600E βCatSTA melanoma model that does not respond to checkpoint inhibitors, PlGF-2123-144-anti-CD40 antibody treatment enhanced T-cell infiltration into the tumors and slowed tumor growth. Together, these results demonstrate the marked therapeutic advantages of engineering matrix-binding domains onto agonistic anti-CD40 antibody as a therapeutic given by tumori-regional injection for cancer immunotherapy.
Implications: Extracellular matrix-binding peptide conjugation to agonistic anti-CD40 antibody enhances antitumor efficacy and reduces treatment-related adverse events. Mol Cancer Ther; 17(11); 2399–411. ©2018 AACR.