bluuebunny/crossref_metadata_2025 huggingface dataset:
The Influence of Diet Quality on Clutch Size and Laying Pattern in Mallards
Authors: Eldrigde Jan L. , Krapu Gary L.
Published: September 2019

We measured the effect of diet quality on variation in the seasonal pattern of Mallard (Anas platyrhynchos) reproduction. Twenty wild-strain hens, consisting of 10 sibling pairs, were maintained in captivity. One sib of each pair was fed an enriched diet, and the other was fed wheat. The wheat diet resulted in reduced clutch size, egg size, laying rate, number of nesting attempts, and total eggs laid. Diet did not affect laying initiation, duration, or the seasonal pattern of change in clutch and egg size with each renest. We believe the variation and pattern observed are adaptations to a highly variable prairie environment where the probability of reproductive success decreases as the season progresses.
Nest-Site Selection and Temporal Patterns in Habitat Use of Roseate and Common Terns
Authors: Burger Joanna , Gochfeld Michael
Published: September 2019

Roseate Terns (Sterna dougallii) nest in a wide variety of habitats. We examined nest-site selection in a mixed-species colony of Roseate and Common (S. hirundo) terns on the interdune area of a barrier beach to determine species differences, to identify which characteristics at nest sites differed from the available habitat, and to compare nest-site preferences of early- and late-nesting Roseate Terns. Both species nested in the same area, but Roseate Terns nested under dense vegetation and Common Terns nested in more open sites. For Roseate Terns, cover within 0.5 m of the nest was greater than that within 1 m; the opposite was true for Common Terns. Cover within 5 m was similar for both species. Roseate and Common terns select different habitat features. Site characteristics of early- and late-nesting Roseate Tern nests differed. Late-nesting terns used sites with greater cover within 0.5 m, less cover within 5 m, taller vegetation, and with less visibility compared with early-nesting terns. Late-nesting Roseate Terns were still able to find sites in dense cover. At this colony, competition between the two species may not be limiting, and abundant sites remain available.
Hypersynchronization in mild cognitive impairment: the ‘X’ model
Authors: Pusil Sandra , López María Eugenia , Cuesta Pablo , Bruña Ricardo , Pereda Ernesto , Maestú Fernando
Published: September 2019

Hypersynchronization has been considered as a biomarker of synaptic dysfunction along the Alzheimeŕs disease continuum. In a longitudinal MEG study, Pusil et al. reveal changes in functional connectivity upon progression from MCI to Alzheimer’s disease. They propose the ‘X’ model to explain their findings, and suggest that hypersynchronization predicts conversion.
Muscle mass and plasma myostatin after exercise training: a substudy of Renal Exercise (RENEXC)—a randomized controlled trial
Authors: Zhou Yunan , Hellberg Matthias , Hellmark Thomas , Höglund Peter , Clyne Naomi
Published: September 2019

Background

Sarcopenia increases as renal function declines and is associated with higher morbidity and mortality. Myostatin is a negative regulator of muscle growth. Its expression in response to exercise is unclear. In this prespecified substudy of the Renal Exercise (RENEXC) trial, we investigated the effects of 12 months of exercise training on sarcopenia, muscle mass and plasma myostatin and the relationships between physical performance, muscle mass and plasma myostatin.

Methods

A total of 151 non-dialysis-dependent patients (average measured glomerular filtration rate 23 ± 8 mL/min/1.73 m2), irrespective of age or comorbidity, were randomly assigned to either strength or balance in combination with endurance training. Body composition was measured with dual-energy X-ray absorptiometry. Plasma myostatin was analysed using enzyme-linked immunosorbent assay kits.

Results

After 12 months, the prevalence of sarcopenia was unchanged, leg and whole-body lean mass increased significantly in the balance group and was unchanged in the strength group. Whole fat mass decreased significantly in both groups. There were no significant between-group differences in sarcopenia or body composition. Plasma myostatin levels increased significantly in both groups, with a significant difference in favour of the strength group. Plasma myostatin was significantly positively related to muscle mass and physical performance at baseline, but these relationships were attenuated after 12 months.

Conclusions

Exercise training seems to be effective in preventing sarcopenia and maintaining muscle mass in non-dialysis-dependent patients with chronic kidney disease (CKD). However, the role of plasma myostatin on muscle mass and physical performance in patients with CKD warrants further study.
Survival, costs, and health care resource use by line of therapy in US Medicare patients with newly diagnosed glioblastoma: a retrospective observational study
Authors: Aly Abdalla , Singh Prianka , Korytowsky Beata , Ling You-Li , Kale Hrishikesh P , Dastani Homa B , Botteman Marc F , Norden Andrew D
Published: September 2019

Background

Glioblastoma (GBM) is associated with poor prognosis, large morbidity burden, and limited treatment options. This analysis evaluated real-world treatment patterns, overall survival, resource use, and costs among Medicare patients with GBM.

Methods

This retrospective observational study evaluated Medicare patients age 66 years or older with newly diagnosed GBM using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data from 2007 through 2013. Patients were followed from diagnosis to death or end of follow-up. An algorithm defined treatment patterns as lines of therapy (LOTs). The Kaplan-Meier method was used to estimate overall survival for the full sample as well as by LOT, surgical resection, Charlson Comorbidity Index (CCI), tumor size, and age. Resource use and costs during the follow-up period were reported in terms of total and per-patient-per-month (PPPM) estimates.

Results

A total of 4308 patients with GBM were identified (median age, 74 years; CCI of 0, 52%). The most commonly used first LOT was temozolomide (82%), whereas chemotherapy + bevacizumab was most prevalent for second-line (42%) and third-line (58%) therapy. The median overall survival was 5.9 months for resected patients and 3 months for unresected patients, with considerable heterogeneity depending on patient characteristics. A great proportion of patients had claims for an ICU admission (86.2%), skilled nursing facility (76.9%), and home health (56.0%) in the postdiagnosis period. The cumulative mean cost was $95 377 per patient and $18 053 PPPM, mostly attributed to hospitalizations.

Conclusions

Limited treatment options, poor survival, and economic burden emphasize the need for novel interventions to improve care for Medicare patients with GBM.
Awareness of axial spondyloarthritis among chiropractors and osteopaths: findings from a UK Web-based survey
Authors: Yong Cee Y , Hamilton Jill , Benepal Jatinder , Griffiths Katie , Clark Zoë E , Rush Amanda , Sengupta Raj , Martindale Jane , Gaffney Karl
Published: September 2019

Objective

Chiropractors and osteopaths are important professional partners in the management of axial spondyloarthritis (axSpA). In view of recent advances in diagnosis and treatment, we sought to understand their current knowledge and working practices.

Methods

A Web-based survey was advertised to chiropractors and osteopaths via the Royal College of Chiropractors and the Institute of Osteopathy.

Results

Of 382 completed responses [237 chiropractors (62%) and 145 osteopaths (38%)], all were familiar with AS, but only 63 and 25% were familiar with the terms axSpA and non-radiographic axSpA, respectively. Seventy-seven per cent were confident with inflammatory back pain. Respondents routinely asked about IBD (91%), psoriasis (81%), acute anterior uveitis (49%), peripheral arthritis (71%), genitourinary/gut infection (56%), enthesitis (30%) and dactylitis (20%). Eighty-seven per cent were aware of the association between axSpA and HLA-B27. Only 29% recognized that axSpA was common in women. Forty per cent recommend an X-ray (pelvic in 80%) and, if normal, 27% would recommend MRI of the sacroiliac joints and whole spine. Forty-four per cent were aware of biologic therapies. Forty-three per cent were confident with the process of onward referral to rheumatology via the general practitioner (GP). The principal perceived barrier to onward referral was reluctance by the GP to accept their professional opinion.

Conclusion

Overall knowledge of ankylosing spondylitis is good, but the term axSpA is poorly understood. Specific learning needs include gender preponderance, awareness of acute anterior uveitis and the availability of biological therapies. There is lack of confidence in the onward referral process to rheumatology via the GP.
P49 Two cases of persistent isolated motor mononeuropathy secondary to etanercept in paediatric population
Authors: MacMahon Jayne M , McHugh John , MacDermott Emma J , Killeen Orla G
Published: September 2019

Background

Juvenile idiopathic arthritis (JIA) is the most common form of inflammatory arthritis in children and has an annual incidence of 33 per 100,000. With the introduction of biologic therapies, the goal of disease remission, both on and off treatment, is becoming increasingly achievable. Etanercept, a TNF-α inhibitor, was the first biologic to be used in JIA and is currently recommended as an add-on therapy in patients with inadequate response to methotrexate alone. While it is generally considered to have a good safety profile, a number of adverse events have been documented, including neuropathy.

Methods

We present two cases of etanercept related mononeuropathy, which persisted despite intravenous immunoglobulin (IVIG) therapy.

Results

Case 1: A 12 year-old girl with polyarticular JIA, who had commenced on etanercept 2 years previously, presented with an acute inability to fully flex her right index finger, associated with intermittent paraesthesia over the area. On examination, there was weakness in the deep flexor digit II and she was unable to flex at the distal interphalangeal joint. Deep tendon reflexes and sensation were normal. Nerve conduction studies showed absence of voluntarily recruited motor potentials in the right flexor digitorum profundus median to right digit II. Etanercept was discontinued and following review by a paediatric neurologist, a course of IVIG was commenced. To date, however, there has been no appreciable clinical improvement.

Case 2: A 7 year-old girl with oligoarticular JIA, who had commenced on etanercept 3 years prior, presented with a ten week history of selective weakness in her left hand and absent power in her flexor pollicis longus. On examination, there was an apparent weakness in her flexor pollicis longus with 0/5 power. Sensory and deep tendon reflexes were normal. Etanercept was discontinued. EMG and nerve conduction studies definitively outruled a proximal median neuropathy or any median motor problem outside of the anterior interosseous nerve. EMG did not find incontrovertible evidence of motor conduction block however this remains a possible and indeed plausible mechanism. She was referred to paediatric neurology and a course of IVIG was commenced.

Conclusion

While etanercept remains a widely used medication in the setting of JIA, these case studies highlight the potential neurological adverse events that can occur. To our knowledge are the first reports of persistent isolated motor neuropathy secondary to etanercept use in the paediatric population.

Conflicts of Interest

The authors declare no conflicts of interest.
P51 Is it injury or inflammation: teenage boy with back pain
Authors: Deepak Samundeeswari , Dandy Tracey , Isles Rachel
Published: September 2019

Background

A 14 year-old boy was referred by an orthopaedic colleague at the district hospital for evaluation of ankylosing spondylitis. The child was previously fit and well. His symptoms reported at the referral was back pain and also possibility of foot drop on the right ankle. His dad had ankylosing spondylitis and was on biologic treatment. Also, there was significant history of autoimmunity in other family members.

Methods

During the initial consultation, we revisited the history. The boy reported that main symptoms were recurrent popping sensation of his right side shoulder associated with pain and burning sensation on the shoulder which usually settles after an hour. He is sporty boy and plays regular rugby, football and used to throw discus. He denied any history of injury or illnesses preceding his symptoms. There was past history of fracture of right ankle on two occasions managed conservatively. There were no other systemic symptoms.

On examination, the child was afebrile and systemically looked well. There was no lymphadenopathy, mouth ulcers or clubbing. His cardio respiratory examination was normal. Abdomen was soft with no organomegaly. He was noted to have winging of scapula on the right side and weakness of the abductor muscles on the right side shoulder. There was wasting of muscles around the right ankle. He was noticed to have bilateral cavovarus and high arched feet. There was scoliosis at the thoracic and lumbar level. His muscle tone, power and reflexes were all normal.

Results

With his clinical presentation of winging of scapula, long thoracic nerve palsy was considered and he was referred to local physiotherapy. MRI spine done at local hospital was reviewed in the MSK radiology meeting and this showed no evidence of ankylosing spondylitis and confirmed scoliosis. His blood tests showed normal full blood count, liver and kidney function, raised creatinine kinase of 358 and HLA B27 positive. The repeat creatinine kinase was normal (153).The nerve conduction study of both the upper and lower limbs were normal. He was also seen by the neurology team. Further discussion with sport medicine colleagues and advised to continue physiotherapy. On the review 3 months later, his symptoms were much improved.

Conclusion

The presentation of a teenage boy with back pain and family history of ankylosing spondylitis warrants further evaluation. Thorough history, examination and early referral to specialist centre is beneficial for appropriate management of complex situations like this.

Conflicts of Interest

The authors declare no conflicts of interest.
P57 Ensuring safe and efficient prescribing: an audit of external prescription requests from the National Centre of Paediatric Rheumatology, Ireland
Authors: Byrne Dearbhla , MacMahon Jayne M , Deely Derek , Peate Karen , O’Gara Emir , MacDermott Emma J , Killeen Orla G
Published: September 2019

Background

Medication prescribing in paediatric rheumatology is closely monitored, particularly as a large number of medications used are either DMARDs or biologic therapy. Within our centre, we aim to give prescriptions when patients are attending outpatient clinics however due to long waiting lists, some patients require prescriptions before their clinic appointment. Currently, this is arranged by parents phoning in to our secretaries, however they often do not have the medication dose or route and this can delay efficient prescribing. We have also found that as most patients have their blood monitoring done in a primary care setting, we do not have access to their results.

The aim of our audit was to formally assess outpatient prescribing in our centre, with a view to streamlining the process.

Methods

Data was collected over a one month period between 05/03/19 and the 05/04/19. Each prescription request was received by our CNS or secretary and passed to the NCHDs. The date and medication required was documented, along with chart availability, last clinic date, last bloods taken, whether the parents gave the dose and if a prescription was ultimately written. All data was analysed using Microsoft Excel.

Results

In total 36 prescriptions were requested. The majority of prescriptions (28) were routine prescriptions, with an additional 6 for ‘emergency’ prescriptions (e.g. diclofenac, ondansetron, NSAIDs and prednisolone) and 2 prescriptions were for a change in medication. Overall, 17 requests were for biologic agents, 7 for methotrexate and 5 for both biologic and methotrexate. Charts were available for 27 patients. Of those not available, 5 parents had given doses with their requests. If doses and charts were not available the dose from the last clinic letter on the system was used. Only in 10 cases out of 36, did parents leave a dose for medication with their prescription request. In total, 21 patients had recent blood tests recorded on our hospital database in the last 3 months and 27 had had clinic appointments in the preceding 6 months, with 13 of these occurring in the preceding 3 months.

Conclusion

This study highlights the large volume of external prescription requests received, as well as the potential for error in prescribing. We are currently planning on introducing a form that parents will be required to complete with all prescription requests, detailing dose and route of medication along with the results of their most recent blood tests. We hope that this will both streamline the process and allow for safer prescribing and plan to re-audit 3 months after its implementation.

Conflicts of Interest

The authors declare no conflicts of interest.
P64 Connecting the dots: towards patient-centric outcome-based RA management: a patient initiative
Authors: Umaashanker Chitra , Shenoy Padmanabha
Published: September 2019

Background

A chronic illness like RA which can result in crippling, chronic pain and disability, needs a fourfold approach to address the wellbeing of the patient, namely physical medicine, suitable diet, mild to moderate exercise and mental/emotional wellbeing. This need for multipronged approach brings its own challenges in the current ecosystem of medical care in India. Adding to the fact that any treatment aimed at control/cure of RA can last for months and years makes the whole process tedious and frustrating at times.

The organisation Parihaar aims to address this challenge by providing continuous support to the patient in order to equip them to become an active partaker in their treatment, and also aims to bring relevant stakeholders together.

Methods

Parihaar addresses the gaps in current ecosystem in chronic autoimmune illness management with help from technology and the internet.

Results

Parihaar is a project that is underway. It is a patient initiative supported by a rheumatologist.

Conclusion

Parihaar is a small step that is addressing a large issue. It is complementary to the current healthcare ecosystem in India, and its success truly depends on adoption and usage.

Conflicts of Interest

The authors declare no conflicts of interest.
A meta-analysis of biologic therapies on risk of new or recurrent cancer in patients with rheumatoid arthritis and a prior malignancy
Authors: Xie Wenhui , Xiao Shiyu , Huang Yanrong , Sun Xiaoying , Gao Dai , Ji LanLan , Li Guangtao , Zhang Zhuoli
Published: September 2019

Objectives

To explore the risk of new and recurrent cancer in adult RA patients with prior malignancy and subsequently exposed to biologic therapies.

Methods

Separate searches were performed of PubMed, EMBASE and Cochrane Library and conference proceedings for observational studies reporting cancer incidence or recurrence in patients with RA and prior malignancy treated with biologics and conventional synthetic DMARDs (csDMARDs). Mantel-Haenszel fixed-effects method was conducted to calculate relative risk and 95% CI.

Results

A total of 12 studies involving 13 598 patients and 32 473 patient-years of follow-up were included (10, 3 and 1 studies for TNF inhibitors [TNFi], rituximab and anakinra, respectively). The crude incidence of new and recurrent cancer per 1000 patient-years were 34.4 for TNFi, 32.3 for rituximab, 32.3 for anakinra and 31.8 for csDMARDs. In the quantitative meta-analysis, biologics were not associated with an increased risk of new or recurrent cancer compared with csDMARDs in patients with RA and prior cancer (TNFi: relative risk = 0.95, 95% CI = 0.83, 1.09; rituximab: relative risk = 0.89, 95% CI = 0.52, 1.53). Secondary analyses of stratification of cancer types, the interval between initiation of TNFi and prior cancer diagnosis, and duration of TNFi exposure, found similar results.

Conclusion

Compared with csDMARDs, there is no increased risk of developing cancer overall or some specific subtypes in RA patients with a prior cancer receiving biologics. More investigations are warranted to explore the risk of cancer development in individual cancer as well as to determine optimal time to initiate biologic therapy after the diagnosis of cancer or completion of cancer treatment.
Managing a Destructive, Episodic Crop Disease: A National Survey of Wheat and Barley Growers’ Experience With Fusarium Head Blight
Authors: Cowger Christina , Smith Joy , Boos Dennis , Bradley Carl A. , Ransom Joel , Bergstrom Gary C.
Published: September 2019

The main techniques for minimizing Fusarium head blight (FHB, or scab) and deoxynivalenol in wheat and barley are well established and generally available: planting of moderately FHB-resistant cultivars, risk monitoring, and timely use of the most effective fungicides. Yet the adoption of these techniques remains uneven across the FHB-prone portions of the U.S. cereal production area. A national survey was undertaken by the U.S. Wheat and Barley Scab Initiative in 17 states where six market classes of wheat and barley are grown. In 2014, 5,107 usable responses were obtained. The highest percentages reporting losses attributable to FHB in the previous 5 years were in North Dakota, Maryland, Kentucky, and states bordering the Great Lakes but across all states, ≥75% of respondents reported no FHB-related losses in the previous 5 years. Adoption of cultivar resistance was uneven by state and market class and was low except among hard red spring wheat growers. In 13 states, a majority of respondents had not applied an FHB-targeted fungicide in the previous 5 years. Although the primary FHB information source varied by state, crop consultants were considered to be an important source or their primary source of information on risk or management of FHB by the largest percentage of respondents. Use of an FHB risk forecasting website was about twice as high in North Dakota as the 17-state average of 6%. The most frequently cited barriers to adopting FHB management practices were weather or logistics preventing timely fungicide application, difficulty in determining flowering timing for fungicide applications, and the impracticality of FHB-reducing rotations. The results highlight the challenges of managing an episodically damaging crop disease and point to specific areas for improvement.
Implementation of the Neonatal Sepsis Calculator in Early-Onset Sepsis and Maternal Chorioamnionitis
Authors: Akangire Gangaram , Simpson Elizabeth , Weiner Julie , Noel-MacDonnell Janelle , Petrikin Joshua , Sheehan Michael
Published: September 2019

Background:

Utilization of the neonatal sepsis calculator published by Kaiser Permanente is rapidly increasing. This freely available online tool can be used in assessment of early-onset sepsis (EOS) in newborns 34 weeks' gestation or more based on maternal risk factors and neonatal examination. However, many hospitals lack standard guidelines for its use, leading to provider discomfort with practice change.

Purpose:

The goal of this project was to study the antibiotic use rate for EOS at a level III neonatal intensive care unit and create standardized guidelines and staff education for using the sepsis calculator. Our ultimate goal was to decrease antibiotic use for EOS in newborns 34 weeks' gestation or more.

Methods:

A standard quality improvement Plan-Do-Study-Act (PDSA) model was utilized with a plan to study the problem, implement the intervention, and test again for improvement. The primary outcome of interest was a decrease in the use of antibiotics for EOS in neonates 34 weeks' gestation or more.

Results:

Over a 4-month period, prior to sepsis calculator implementation, antibiotic use for suspected EOS was 11% and blood culture was done on 14.8% of live births. After implementation of the sepsis calculator and completion of the PDSA cycle, sepsis calculator use was greater than 95%, antibiotic use dropped significantly to 5% (P = .00069), and blood culture use dropped to 7.6% (P = .00046).

Implications for Practice:

Staff education and systematic intervention using a PDSA model can significantly impact patient care, decreasing the administration of antibiotics to infants at risk for sepsis.

Implications for Research:

Future research is needed to decrease antibiotic use in premature infants less than 34 weeks' gestation with similar risk factors and clinical features.

Video Abstract available at
https://journals.na.lww.com/advancesinneonatalcare/Pages/videogallery.aspx?videoId=34&autoPlay=true
National Burden of Hospitalization Due to Cutaneous Melanoma in Adolescents and Young Adults
Authors: Tripathi Raghav , Knusel Konrad D. , Ezaldein Harib H. , Bordeaux Jeremy S. , Scott Jeffrey F.
Published: September 2019

Objectives:

Although adolescents and young adults (AYA) suffer disproportionately from cutaneous melanoma (CM), little is known regarding the burden of CM leading to hospitalization in AYA. The objective of this study was to elucidate sociodemographic/hospitalization characteristics of AYA CM inpatients, determine which factors lead to the greater length of stay (LOS) and cost of care for AYA CM inpatients, and evaluate trends in the prevalence, LOS, and cost of care for AYA CM hospitalizations.

Materials and Methods:

A retrospective cohort study of nationally representative data from the 2009 to 2015 National Inpatient Sample. Multivariable survey-weighted logistic regression models were used to determine sociodemographic factors associated with AYA CM hospitalization. Multivariable survey-weighted linear regression models were used to determine characteristics associated with the greater cost of care and LOS in AYA CM inpatients.

Results:

A total of 8986 AYA CM inpatients were included in this study. The prevalence of AYA CM hospitalizations is decreasing over time while the cost of care is increasing. On average, AYA CM hospitalizations were 3.3 days long and cost $38,018.40. Controlling for all covariates, male sex, older age, non-Hispanic white race, higher income, private insurance, and elective admissions were associated with AYA hospitalization due to CM (P<0.0001). Male sex was associated with longer LOS (P=0.007) and cost of care (P=0.01) among AYA hospitalized for CM.

Conclusions:

Despite a decreasing prevalence of CM hospitalizations in AYA inpatients, the economic burden of these hospitalizations is increasing. Substantial sex-based differences exist in the inpatient burden of AYA CM. Further research is required to elucidate the causes of these differences and prevent AYA hospitalization due to CM.
Associations of IL-12, IL12R polymorphisms and serum IL-12 levels with high-risk human papillomavirus susceptibility in rural women from Luohe, Henan, China
Authors: Song Jiayu , Zhang Qingwei , Wang Rong , Sun Mingzhen , Jin Shaoju
Published: September 2019

Background:

Interleukin 12 (IL-12) and interleukin 12 receptor (IL12R), key inflammatory cytokines in the immune system, participate in bridging the innate immunity and adaptive immunity. No previous work has reported the role of IL-12 and IL12R in high-risk human papillomavirus (hrHPV) susceptibility. The purpose of this study was to investigate the association of IL-12, IL12R polymorphisms, and serum IL-12 levels with hrHPV susceptibility in rural women from Luohe, Henan, China.

Methods:

Two hundred sixty cases with hrHPV infection and 260 healthy controls were selected. Enzyme-linked immunosorbent assays were used to detect the serum IL-12 levels, and the polymorphisms of IL12B rs3212227, IL12RB1 rs393548, and IL12RB1 rs436857 were determined using DNA sequencing.

Results:

The serum IL-12 levels were significantly lower in cases with hrHPV infection compared with those in healthy controls (P < .01).There was no significant difference in IL12 rs3212227, IL12RB1rs436857, and IL12RB1rs393548 genotype and allele frequencies between cases and controls (P > .05). Furthermore, with respect to the IL12 rs3212227 polymorphism with serum IL-12 levels, although serum IL-12 levels were lower in cases than in controls, we did not find any differences between serum IL-12 levels and genotypes in cases(P > .05).

Conclusions:

Our data demonstrates that low serum IL-12 levels may be associated with hrHPV susceptibility but are not associated with IL-12 gene polymorphisms; furthermore, IL-12 and IL12R gene polymorphisms may not contribute susceptibility to hrHPV in rural women from Luohe, Henan, China.
Arterial wall structural changes in noncirrhotic chronic hepatitis C patients
Authors: Sliem Hamdy A. , Salem Ahmed S. , Hussien Walid M. , El Sayed Hind R.A.
Published: September 2019

Background

Hepatitis C virus (HCV) infection is a major overall health predicament. Patients with HCV infection may progress to hepatic and extrahepatic complications. There are emerging groups of data on accelerated vascular changes triggering subclinical atherosclerosis. Nevertheless, whether these changes are associated with an increased risk of morbidity and mortality is unclear.

Aim

To determine subclinical arterial wall structural changes in noncirrhotic chronic hepatitis C patients and the impact of possible cofactors.

Patients and methods

Forty-two patients with noncirrhotic chronic HCV and 42 healthy controls matched in terms of age and sex were subjected to clinical, biochemical, and imaging measures for the evaluation of arterial wall changes (aortic elasticity/stiffness and carotid intima-media thickness). Elasticity was evaluated by measuring the aortic diameter and pulse wave velocity.

Results

Nonsignificant greater mean aortic diameter was found among the cases than the control group (P = 0.67). The mean carotid intima-media thickness was quite similar in both groups (P = 0.12). The mean pulse wave velocity measures were twice those in the cases than the control group, indicating greater tendencies toward arterial stiffness among patients with HCV (P < 0.001). There was no significant relationship between any of the laboratory investigations (lipid and HCV-RNA values) and any of the vascular imaging investigations.

Conclusion

Aortic diameter and aortic stiffness are increased among chronic hepatitis C patients than healthy controls; however, there is no significant difference in carotid intima thickness.
Comparisons of Depression, Sexual Function, and Quality of Life Between Women With Gynecological Cancers and Race-Matched Healthy Controls
Authors: Bai Jinbing , Belcher Sarah M. , Meador Rebecca , Daniel Gaea , Shelton Joseph , Patel Pretesh , Dolan Mary , Arluck Jessica , Khanna Namita , Horowitz Ira , Liu Tian , Watkins Bruner Deborah
Published: September 2019

Background

Although higher incidence and mortality of gynecological cancer (GynCa) are documented in black compared with white women, few studies have documented quality of life (QOL) or healthy control comparisons.

Objective

This study compared depression, sexual function, and QOL between patients with GynCa and race-matched healthy controls.

Methods

Patients with GynCa and healthy controls completed the Patient Health Questionnaire-9, Female Sexual Function Index, and Functional Assessment of Cancer Therapy–General measures at baseline; GynCa patients were assessed again at 6 months post–radiation therapy (RT).

Results

Analyses included 84 participants (51% white, 49% black), including 28 GynCa patients and 56 controls with similar marital status. Compared with healthy controls, patients were younger, had a higher body mass index, and had more depression (P = .01); 82% of the patients and 71% of the healthy controls met criteria for sexual dysfunction at baseline (P = .29). Patients pre-RT had greater sexual dysfunction and lower QOL (P = .001) than controls did; patients at 6-month post-RT showed improved sexual function scores compared with pre-RT, with similar results to controls. White GynCa patients reported less sexual desire (P = .02), more pain (P = .05), and lower total Female Sexual Function Index scores (P = .01) than did black GynCa patients. Both black and white GynCa patients reported lower total QOL than their race-matched controls did (P = .07 and P = .002).

Conclusions

Women with GynCa reported more depression and lower QOL than did healthy controls pre-RT. Among GynCa patients, white women had more sexual dysfunction than black women did.

Implications for Practice

The differences in sexual dysfunction between white and black women with GynCa suggest developing guidelines directing routine sexual assessment and rehabilitation in women treated for GynCa.
Point mass dynamics on spherical hypersurfaces
Authors: Dritschel David G.
Published: September 2019

The equations of motion are derived for a system of point masses on the (hyper)surface

S

n

of a sphere embedded in

R

n
+
1

for any dimension
n
 > 1. Owing to the symmetry of the surface, the equations take a particularly simple form when using the Cartesian coordinates of

R

n
+
1

. The constraint that the distance of the
j
th mass ∥

r

j

∥ from the origin remains constant (i.e. each mass remains on the surface) is automatically satisfied by the equations of motion. Moreover, the equations are a Hamiltonian system with a conserved energy as well as a host of conserved angular momenta. Several examples are illustrated in dimensions
n
 = 2 (the sphere) and
n
 = 3 (the glome).

This article is part of the theme issue ‘Topological and geometrical aspects of mass and vortex dynamics’.
Gels for Live Analysis of Compartmentalized Environments (GLAnCE): A Tissue Model to Probe Tumour Phenotypes at Tumour-Stroma Interfaces
Authors: D’Arcangelo Elisa , Wu Nila C. , Chen Tianhao , Shahaj Andi , Cadavid Jose L. , Huang Linwen , Ailles Laurie , McGuigan Alison P.
Published: September 2019

The interface between a tumour and the adjacent stroma is a site of great importance for tumour development. At this site, carcinoma cells are highly proliferative, undergo invasive phenotypic changes, and directly interact with surrounding stromal cells, such as cancer-associated fibroblasts (CAFs) which further exert pro-tumorigenic effects. Here we describe the development of GLAnCE (Gels for Live Analysis of Compartmentalized Environments), an easy-to-use hydrogel-culture platform for investigating CAF-tumour cell interaction dynamics in vitro at a tumour-stroma interface. GLAnCE enables observation of CAF-mediated enhancement of both tumour cell proliferation and invasion at the tumour-stroma interface in real time, as well as stratification between phenotypes at the interface versus in the bulk tumour tissue compartment. We found that CAF presence resulted in the establishment of an invasion-permissive, interface-specific matrix environment, that leads to carcinoma cell movement outwards from the tumour edge and tumour cell invasion. Furthermore, the spatial stratification capability of GLAnCE was leveraged to discern differences between tumour cell epithelial-to-mesenchymal (EMT) transition genes induced by paracrine signaling from CAFs versus genes induced by interface-specific, CAF-mediated microenvironment. GLAnCE combines high usability and tissue complexity, to provide a powerful in vitro platform to probe mechanisms of tumour cell movement specific to the microenvironment at the tumour-stroma interface.
ATF4 regulates neuronal death in models of Parkinson’s Disease
Authors: Demmings Matthew D. , Petroff Gillian N. , Tarnowski-Garner Heather E. , Cregan Sean P.
Published: September 2019

Parkinson’s Disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra resulting in severe motor impairments. However, the mechanisms underlying this neuronal loss remain largely unknown. Activating Transcription Factor 4 (ATF4), a key mediator of the Integrated Stress Response (ISR), is a transcription factor that during prolonged activation can induce the expression of pro-apoptotic target genes. Oxidative stress and ER stress have been implicated in PD and these factors are known to activate the ISR. In this study, we have determined, that both PD neurotoxins (MPP+ and 6-OHDA) and α-synuclein aggregation induced by pre-formed human alpha-synuclein fibrils (PFFs) cause sustained upregulation of ATF4 expression in mouse primary cortical and mesencephalic neurons. Furthermore, we demonstrate that PD neurotoxins induce the expression of the pro-apoptotic factors Chop, Trb3 and Puma in an ATF4-dependent manner. Importantly, using neurons derived from ATF4 +/+ and ATF4 -/- mice, we demonstrate that ATF4 promotes neuronal apoptosis and dopaminergic cell loss in cellular models of PD. Finally, we demonstrate that the eIF2α kinase inhibitor C16 suppresses MPP+ and 6-OHDA induced ATF4 activation and protects against PD neurotoxin induced neuronal death. Taken together these results indicate that ATF4 is a key regulator of dopaminergic cell death induced by PD neurotoxins and pathogenic α-synuclein aggregates and highlight the ISR as a potential therapeutic target in PD.
Increases in structural shortest path lengths provide information about the distal neurophysiological consequences of focal brain lesions
Authors: Griffis Joseph C. , Metcalf Nicholas V. , Corbetta Maurizio , Shulman Gordon L.
Published: September 2019

Focal brain lesions disrupt resting-state functional connectivity, but the underlying structural mechanisms are unclear. Here, we examined the direct and indirect effects of structural disconnections on resting-state functional connectivity in a large sample of sub-acute stroke patients with heterogeneous brain lesions. We defined direct disconnections as the loss of direct structural connections between two regions, and indirect disconnections as increases in the shortest structural path length between two regions that lack direct structural connections. On average, nearly 20% of all region pairs suffered either a direct or indirect disconnection by the lesions in our sample. Importantly, both directly and indirectly disconnected region pairs showed more severe functional connectivity disruptions than region pairs with spared direct and indirect connections, respectively, although functional connectivity disruptions tended to be most severe between region pairs that sustained direct structural disconnections. Together, these results emphasize the widespread impacts of focal brain lesions on the structural connectome, and show that these impacts are reflected by disruptions of the functional connectome. Further, they indicate that in addition to direct structural disconnections, lesion-induced increases in the structural shortest path lengths between indirectly structurally connected region pairs provide information about the remote functional disruptions caused by focal brain lesions.
Cerebral perfusion and metabolism coupling during a critical time window provides rapid assessment of cardiac arrest severity and prognosis in a preclinical model
Authors: Wilson R. H. , Crouzet C. , Torabzadeh M. , Bazrafkan A. , Maki N. , Alcocer J. , Tromberg B. J. , Choi B. , Akbari Y.
Published: September 2019

Improved quantitative understanding of the dynamic relationship among cerebral blood flow, oxygen consumption, and electrical activity is important to clinicians treating acute brain injury. Such knowledge would elucidate the neurovascular response to ischemia, helping to potentially guide treatment. Using a multimodal optical imaging platform and a clinically-relevant rat model of cardiac arrest (CA) and cardiopulmonary resuscitation (CPR), we continuously measured cerebral blood flow (CBF), brain tissue oxygenation (StO2), cerebral metabolic rate of oxygen (CMRO2), and cerebral electrical activity (electrocorticography; ECoG). Multiple phases of cerebral hemodynamic recovery, with different degrees of mismatch between CBF and CMRO2, were observed following CPR. At 1 min post-resuscitation, we observed that the ratio CBF/CMRO2 is indicative of CA duration/severity and prognostic (with 87% accuracy) of short-term neurological recovery measured by the re-initiation of ECoG activity. These measurements provide the earliest known metrics for assessment of CA severity and prognosis post-CPR. Interestingly, the accuracy of this information is lost beyond 2-3 minutes post-CPR, highlighting a critical, easily overlooked, period immediately post-CPR. These metrics do not require pre-resuscitation data, underscoring translational potential in emergency-response settings when pre-CA information is unavailable. These metrics encourage validation in human studies, potentially offering real-time feedback during CA/CPR to optimize neurological outcome.
Antigenicity and Potential Use of A Novel Brucella Multiepitope Recombinant Protein in the Diagnosis of Brucellosis
Authors: Yin Dehui , Bai Qiongqiong , Li Li , Xu Lichun , Xu Kun , Li Juan
Published: September 2019

Currently, brucellosis is a reemerged zoonotic infectious disease with an increased incidence in recent years. A simple, rapid and sensitive method for diagnosing brucellosis has important significance for early diagnosis and early treatment, which can help to reduce medical burden and economic loss. Previously, a multiple epitope recombinant protein was constructed based on linear B-cell epitope prediction tools. In this study, the recombinant protein was used as an antigen to study the immune response produced by immunized mice, and goat serum was used to verify its diagnostic accuracy.The production of antibodies was successfully induced in the vaccinated mice. Through analyzing the serum antibody subtypes, the primary antibody was identified as IgG. Flow cytometric analysis revealed that the percentage of CD4+, CD8+ and the CD4+/CD8+ ratios were increased by T cell subsets in mouse splenocytes, indicating that the recombinant protein induced a strong immune response in mice and that it had strong immunoreactivity. Using indirect ELISA, the recombinant protein correctly diagnosed positive and negative brucellosis samples. Compared with the whole bacterial antigen, the recombinant protein had a weaker sensitivity but a stronger specificity.In this study, animal experiments showed that the recombinant protein had good antigenicity, and indirect ELISA indicates that it can be used as an antigen to diagnose brucellosis. Therefore, the recombinant protein is a potential candidate antigen for brucellosis vaccine development and serological diagnosis.
HaploHide: A Data Hiding Framework for Privacy Enhanced Sharing of Personal Genetic Data
Authors: Harmanci Arif , Jiang Xiaoqian , Zhi Degui
Published: September 2019

Personal genetic data is becoming a digital commodity as millions of individuals have direct access to and control of their genetic information. This information must be protected as it can be used for reidentification and potential discrimination of individuals and relatives. While there is a great incentive to share and use genetic information, there are limited number of practical approaches for protecting it when individuals would like to make use of their genomes in clinical and recreational settings. To enable privacy-enhanced usage of genomic data by individuals, we propose a crowd-blending-based framework where portions of the individual’s haplotype is “hidden” within a large sample of other haplotypes. The hiding framework is motivated by the existence of large-scale population panels that we utilize for generation of the crowd of haplotypes in which the individual’s haplotype is hidden. We demonstrate the usage of hiding in two different scenarios: Sharing of variant alleles on genes and sharing of GWAS variant alleles. We evaluate hiding framework by testing reidentification of hidden individuals using numerous measures of individual reidentification. In these settings, we discuss how effective hiding can be accomplished when the adversary does not have access to auxiliary identifying information. Compared to the existing approaches for protecting privacy, which require substantial changes in the computational infrastructure, e.g., homomorphic encryption, hiding-based framework does not incur any changes to the infrastructure. However, the processing must be performed for every sample in the crowd and therefore data processing cost will increase as the crowd size increases.
Mechanism of gating and partial agonist action in the glycine receptor
Authors: Yu Jie , Zhu Hongtao , Lape Remigijus , Greiner Timo , Shahoei Rezvan , Wang Yuhang , Du Juan , Lü Wei , Tajkhorshid Emad , Sivilotti Lucia , Gouaux Eric
Published: September 2019

The glycine receptor is a pentameric, neurotransmitter-activated ion channel that transitions between closed/resting, open and desensitized states. Glycine, a full agonist, produces an open channel probability (Po) of ∼1.0 while partial agonists, such as taurine and γ-amino butyric acid (GABA) yield submaximal Po values. Despite extensive studies of pentameric Cys-loop receptors, there is little knowledge of the molecular mechanisms underpinning partial agonist action and how the receptor transitions from the closed to open and to desensitized conformations. Here we use electrophysiology and molecular dynamics (MD) simulations, together with a large ensemble of single particle cryo-EM reconstructions, to show how agonists populate agonist-bound yet closed channel states, thus explaining their lesser efficacy, yet also populate agonist-bound open and desensitized states. Measurements within the neurotransmitter binding pocket, as a function of bound agonist, provide a metric to correlate the extent of agonist-induced conformational changes to open channel probability across the Cys-loop receptor family.
Initial data release and announcement of the Fish10K: Fish 10,000 Genomes Project
Authors: Fan Guanngyi , Song Yue , Huang Xiaoyun , Yang Liandong , Zhang Suyu , Zhang Mengqi , Yang Xianwei , Chang Yue , Zhang He , Li Yongxin , Liu Shanshan , Yu Lili , Seim Inge , Feng Chenguang , Wang Wen , Wang Kun , Wang Jing , Xu Xun , Yang Huanming , Chen Nansheng , Liu Xin , He Shunping
Published: September 2019

With more than 30,000 species, fish are the largest and most ancient vertebrate group. Despite their critical roles in many ecosystems and human society, fish genomics lags behind work on birds and mammals. This severely limits our understanding of evolution and hinders progress on the conservation and sustainable utilization of fish. Here, we announce the Fish10K project, an international collaborative project or initiative? aiming to sequence 10,000 representative fish genomes under a systematic context within ten years, and officially welcome collaborators to join this effort. As a step towards this goal, we herein describe a feasible workflow for the procurement and storage of biospecimens, and sequencing and assembly strategies. To illustrate, we present the genomes of ten fish species from a cohort of 93 species chosen for technology development.