bluuebunny/crossref_metadata_2025 huggingface dataset:
Bordetella pertussis Infection in Infants and Young Children in Shanghai, China, 2016–2017: Clinical Features, Genotype Variations of Antigenic Genes and Macrolides Resistance
Authors: Fu Pan , Wang Chuanqing , Tian He , Kang Zhihua , Zeng Mei
Published: August 2018

Background:

The global resurgence of pertussis in countries with high vaccination coverage has been a concern of public health.

Methods:

Nasopharyngeal swabs were collected for Bordetella pertussis culture from children with suspected pertussis. Clinical and vaccination information were reviewed through electronic medical chart and immunization record. Antibiotics susceptibility was evaluated using E-test for erythromycin, azithromycin, clarithromycin and sulfamethoxazole/trimethoprim. The MLST genotypes and 7 antigenic genes (ptxP, ptxA, ptxC, Prn, fim3, fim2 and tcfA) of Bordetella pertussis were identified by polymerase chain reaction amplification and sequencing.

Results:

During January 2016 to September 2017, a total of 141 children 1–48 months of age were culture-confirmed with pertussis, of whom 98 (69.5%) were younger than 6 months, 25 (17.7%) had completed at least 3 doses of DTaP and 75 (53.2%) had a clear exposure to household members with persistent cough. Fully vaccinated cases manifested milder disease than unvaccinated and not-fully vaccinated cases. All strains were MLST2. High-virulent strains characteristic of ptxP3/prn2/ptxC2 constituted 41.1% (58/141) and were all susceptible to macrolides while low-virulent strains characteristic of ptxP1/prn1/ptxC1 constituted 58.9% (83/141) and 97.6% (81/83), respectively, were highly resistant to macrolides.

Conclusions:

Pertussis is resurging among infants and young children in Shanghai, and household transmission is the main exposure pathway. The high-virulent strains harboring ptxP3/prn2/ptxC2 and the macrolide-resistant Bordetella pertussis strains are quite prevalent. These issues impose a public health concern in Shanghai. Our findings are important to modify the DTaP vaccination strategy and the management guideline of pertussis in China.
Pharmacokinetics and Safety of Single Intravenous Doses of Ceftolozane/Tazobactam in Children With Proven or Suspected Gram-Negative Infection
Authors: Bradley John S. , Ang Jocelyn Y. , Arrieta Antonio C. , Larson Kajal B. , Rizk Matthew L. , Caro Luzelena , Yang Shan , Yu Brian , Johnson Matthew G. , Rhee Elizabeth G.
Published: August 2018

Background:

Drug-resistant Gram-negative bacteria are a growing threat to children; thus new antibiotics are needed to treat infections caused by these pathogens. Ceftolozane/tazobactam is active against many Gram-negative pathogens and is approved for treatment of complicated intra-abdominal and urinary tract infections in adults, but has not been evaluated in children.

Methods:

This phase 1, noncomparative, open-label, multicenter study characterized the pharmacokinetics (by noncompartmental analysis), safety, and tolerability of single intravenous doses of ceftolozane/tazobactam in pediatric patients (birth [7 days postnatal] to < 18 years of age) with proven/suspected Gram-negative infection or receiving perioperative prophylaxis (clinicaltrials.gov NCT02266706). Patients were enrolled into 1 of 6 age groups to receive a single, age-based ceftolozane/tazobactam dose, with timed blood sample collection for determining plasma concentrations of ceftolozane and tazobactam. Safety and tolerability were also evaluated.

Results:

Thirty-seven patients received study drug; 34 were included in the pharmacokinetic population. Ceftolozane and tazobactam pharmacokinetic parameters were generally comparable for patients 3 months to < 18 years of age. Patients from birth (7 days postnatal) to < 3 months of age had lower clearance than older children, likely due to the immature renal function of these young infants. No deaths, study drug-related serious adverse events, or clinically significant laboratory abnormalities were observed after administration of ceftolozane/tazobactam.

Conclusions:

The doses evaluated in this study yielded ceftolozane/tazobactam exposure levels generally comparable with those in adults. Single doses of ceftolozane/tazobactam were well-tolerated, and no safety concerns were identified. These data informed pharmacokinetic/pharmacodynamic models to derive pediatric dose recommendations for phase 2 ceftolozane/tazobactam clinical trials.
Influenza-associated Hospitalization in Children Younger Than 5 Years of Age in Suzhou, China, 2011–2016
Authors: Yu Jia , Zhang Xiyan , Shan Wei , Gao Junmei , Hua Jun , Tian Jianmei , Ding Yunfang , Zhang Jun , Chen Liling , Song Ying , Zhou Suizan , Iuliano A. Danielle , Greene Carolyn M. , Zhang Tao , Zhao Genming
Published: August 2018

Background:

Studying the burden and risk factors associated with severe illness from influenza infection in young children in eastern China will contribute to future cost-effectiveness analyses of local influenza vaccine programs.

Methods:

We conducted prospective, severe acute respiratory infection (SARI) surveillance at Suzhou University–Affiliated Children’s Hospital to estimate influenza-associated hospitalizations in Suzhou University–Affiliated Children’s Hospital by month in children younger than 5 years of age from October 2011 to September 2016. SARI was defined as fever (measured axillary temperature ≥ 38°C) and cough or sore throat or inflamed/red pharynx in the 7 days preceding hospitalization. We combined SARI surveillance data with healthcare utilization survey data to estimate and characterize the burden of influenza-associated SARI hospitalizations in Suzhou within this age group in the 5-year period.

Results:

Of the 36,313 SARI cases identified, 2,297 from respiratory wards were systematically sampled; of these, 259 (11%) were influenza positive. Estimated annual influenza-associated SARI hospitalization rates per 1,000 children younger than 5 years of age ranged from 4 (95% confidence interval [CI], 2–5) in the 2012–2013 season to 16 (95% CI, 14–19) in the 2011–2012 season. The predominant viruses were A/H3N2 (59%) in 2011–12, both A/H1N1pdm09 (42%) and B (46%) in 2012–13, A/H3N2 (71%) in 2013–14, A/H3N2 (55%) in 2014–15 and both A/H1N1pdm09 (50%) and B (50%) in 2015–16. The age-specific influenza-associated SARI hospitalization rates for the 5-year period were 11 (95% CI, 8–15) per 1,000 children 0–5 months of age; 8 (95% CI, 7–10) per 1,000 children 6–23 months of age and 5 (95% CI, 4–5) per 1,000 children 24–59 months of age, respectively.

Conclusions:

From 2011 to 2016, influenza-associated SARI hospitalization rates in children aged younger than 5 years of age in Suzhou, China, were high, particularly among children 0–5 months of age. Higher hospitalization rates were observed in years where the predominant circulating virus was influenza A/H3N2. Immunization for children > 6 months, and maternal and caregiver immunization for those < 6 months, could reduce influenza-associated hospitalizations in young children in Suzhou.
Use of Triple Combination Antiretroviral Therapy With Raltegravir as Empiric HIV Therapy in the High-risk HIV-exposed Newborn
Authors: Trahan Marie-Julie , Lamarre Valérie , Metras Marie-Elaine , Kakkar Fatima
Published: August 2018

The recent approval of raltegravir granules for suspension in the newborn population offers a new option for the antiretroviral prophylaxis of newborns for the prevention of perinatal transmission. However, there are little data on its use in preterm infants, nor on outcomes following its use as empiric HIV therapy for newborns subsequently found to be infected. We describe here the use of RAL granules for suspension in these cases.
Tetrodotoxin-sensitive voltage-gated sodium channels regulate bladder afferent responses to distension
Authors: Grundy Luke , Erickson Andelain , Caldwell Ashlee , Garcia-Caraballo Sonia , Rychkov Grigori , Harrington Andrea , Brierley Stuart M.
Published: August 2018

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a prevalent, chronic bladder disorder that negatively impacts the quality of life for ∼5% of the western population. Hypersensitivity of mechanosensory afferents embedded within the bladder wall is considered a key component in mediating IC/BPS symptoms. Bladder infusion of voltage-gated sodium (Nav) channel blockers show clinical efficacy in treating IC/BPS symptoms; however, the current repertoire of Navchannels expressed by and contributing to bladder afferent function is unknown. We used single-cell reverse-transcription polymerase chain reaction of retrogradely traced bladder-innervating dorsal root ganglia (DRG) neurons to determine the expression profile of Navchannels, and patch-clamp recordings to characterise the contribution of tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) Navchannels to total sodium current and neuronal excitability. We determined the TTX-S and TTX-R contribution to mechanosensitive bladder afferent responses ex vivo and spinal dorsal horn activation in vivo. Single-cell reverse-transcription polymerase chain reaction of bladder-innervating DRG neurons revealed significant heterogeneity in Navchannel coexpression patterns. However, TTX-S Navchannels contribute the vast majority of the total sodium current density and regulate the neuronal excitability of bladder DRG neurons. Furthermore, TTX-S Navchannels mediate almost all bladder afferent responses to distension. In vivo intrabladder infusion of TTX significantly reduces activation of dorsal horn neurons within the spinal cord to bladder distension. These data provide the first comprehensive analysis of Navchannel expression within sensory afferents innervating the bladder. They also demonstrate an essential role for TTX-S Navchannel regulation of bladder-innervating DRG neuroexcitability, bladder afferent responses to distension, and nociceptive signalling to the spinal cord.
Do patients with interictal migraine modulate pain differently from healthy controls? A psychophysical and brain imaging study
Authors: Kisler Lee B. , Granovsky Yelena , Coghill Robert C. , Sprecher Elliot , Manor David , Yarnitsky David , Weissman-Fogel Irit
Published: August 2018

Studies in interictal migraine show either normal or impaired pain modulation, at the psychophysical level. To date, pain modulation in migraineurs has yet to be explored concurrent with imaging methods. We aimed to investigate brain activity associated with endogenous analgesia by functional magnetic resonance imaging in attack-free migraineurs. Thirty-nine episodic migraineurs and 35 controls participated. Endogenous analgesia efficiency was assessed by the conditioned pain modulation (CPM) paradigm during functional magnetic resonance imaging. Conditioned pain modulation included 4 stimulation sequences of either test stimulus (noxious contact heat at forearm) given stand alone (Ts_alone) or concomitant to contralateral foot immersion in cold water (Ts_conditioned). The psychophysical CPM (Ts_conditioned minus Ts_alone; 0-10 numerical rating scale) and related brain activity were examined. No group differences were found in the psychophysical CPM (controls: −0.52 ± 0.80; migraineurs: −0.20 ± 0.88; repeated-measures analysis of variance: P = 0.110) or related brain activity (family wise error [P < 0.05] correction at the voxel level). Within groups, controls showed a significant CPM effect (Ts_alone: 6.15 ± 2.03 vs Ts_conditioned: 5.63 ± 1.97; P < 0.001), whereas migraineurs did not (Ts_alone: 5.60 ± 1.92 vs Ts_conditioned: 5.39 ± 2.30; P = 0.153); yet, both groups showed significant CPM-related decreased deactivation in prefrontal areas including the superior frontal gyrus and parietal regions including precuneus. The change in brain activity seems related to task demands rather than to pain reduction. The lack of group difference between migraineurs and controls in CPM and its related brain activity may result from (1) the specific CPM methodology used in this study, since migraineurs are reported to show various pain modulation efficiency for different test paradigms and/or (2) pathophysiological diversity of patients with migraine.
Structural, functional, and symptom relations in painful distal symmetric polyneuropathies: a systematic review
Authors: Karlsson Pall , Hincker Alexander M. , Jensen Troels Staehelin , Freeman Roy , Haroutounian Simon
Published: August 2018

The diagnosis of distal symmetric polyneuropathies (DSPs) relies on the presenting symptomatology and neurological sensory examination, supported by objectively quantified structural and functional changes in sensory nerves. Although these separate components have important diagnostic utility, the associations between the structural vs the symptomatic and functional findings in painful DSP are still unclear. It is assumed that delineation of the correlations, or lack of such, between structure, clinical presentation, and function will contribute to a better understanding and treatment of DSP. This systematic review assessed small fiber morphology in patients with different types of painful DSP, and compared it with symptoms, signs, and nerve fiber function. Overall, 111 papers met the inclusion criteria for the systematic review. The results indicate that epidermal nerve fiber loss, in isolation, is not a useful indicator of painful symptoms or their severity in DSP. Intraepidermal nerve fiber density correlated reasonably well with neuropathy scores on tools assessing signs and symptoms (such as the Michigan Neuropathy Screening Instrument and the Total Neuropathy Score), but less so with symptom measures only. Among various psychophysical sensory measures, warmth detection and heat pain thresholds correlated best with intraepidermal nerve fiber density, particularly when assessed at the same anatomical site. The observed sources of heterogeneity, and the lack of associations between structural and functional measures in several studies are discussed. A framework is proposed for uniform assessment of nerve fiber parameters for investigating clinically relevant mechanisms of neuropathic pain in DSP.
Salivary Cortisol Profile Under Different Stressful Situations in Female College Students: Moderating Role of Anxiety and Sleep
Authors: Suh Minhee
Published: August 2018

Objectives: This study investigated the level of cortisol under different stressful situations and its relationship with sleep and anxiety in female college students. Methods: Salivary cortisol was measured 6 times a day during a routine period free of examination stress and a stressful period. Area under the curve (AUC) was calculated for cortisol level for awakening response (AUCAG) and during the day (AUCTG). Sleep characteristics and anxiety were measured using an actigraph and the Spielberger State-Trait Anxiety Inventory, respectively, during the different periods. Results: Thirty-six people participated in the study. During the stressful period, anxiety had a positive correlation with sleep efficiency (P = .020), wake after sleep onset (P = .023), and mean wake episodes during sleep (P = .048). Poorer sleep efficiency (P = .014), greater wake after sleep onset (P = .008), and mean wake episodes during sleep (P = .044) were significantly associated with less AUCAG. Trait anxiety was significantly higher in participants with greater AUCTG (P = .008). Conclusions: Female college students with increased anxiety under the stressful situation slept better. Those with poor sleep showed attenuated morning cortisol secretion. Those with higher trait anxiety had greater cortisol during the day.
Cannabis and the Health and Performance of the Elite Athlete
Authors: Ware Mark A. , Jensen Dennis , Barrette Amy , Vernec Alan , Derman Wayne
Published: August 2018

Objective:

Cannabis (marijuana) is undergoing extensive regulatory review in many global jurisdictions for medical and nonmedical access. Cannabis has potential impact on the health of athletes as well as on performance in both training and in competition. The aim of this general review is to identify and highlight the challenges in interpreting information with respect to elite athletic performance, and to point to important research areas that need to be addressed.

Data Sources:

A nonsystematic literature review was conducted using Medline and PubMed for articles related to cannabis/marijuana use and sports/athletic performance; abstracts were reviewed by lead author and key themes identified and explored.

Main Results:

Cannabis may be primarily inhaled or ingested orally for a range of medical and nonmedical reasons; evidence for efficacy is limited but promising for chronic pain management. Although evidence for serious harms from cannabis use on health of athletes is limited, one should be cognizant of the potential for abuse and mental health issues. Although the prevalence of cannabis use among elite athletes is not well-known, use is associated with certain high-risk sports. There is no evidence for cannabis use as a performance-enhancing drug.

Conclusions:

Medical and nonmedical cannabis use among athletes reflects changing societal and cultural norms and experiences. Although cannabis use is more prevalent in some athletes engaged in high-risk sports, there is no direct evidence of performance-enhancing effects in athletes. The potential beneficial effects of cannabis as part of a pain management protocol, including reducing concussion-related symptoms, deserve further attention.
Low Vision Enhancement with Head-mounted Video Display Systems: Are We There Yet?
Authors: Deemer Ashley D. , Bradley Christopher K. , Ross Nicole C. , Natale Danielle M. , Itthipanichpong Rath , Werblin Frank S. , Massof Robert W.
Published: August 2018

SIGNIFICANCE

Head-mounted video display systems and image processing as a means of enhancing low vision are ideas that have been around for more than 20 years. Recent developments in virtual and augmented reality technology and software have opened up new research opportunities that will lead to benefits for low vision patients. Since the Visionics low vision enhancement system (LVES), the first head-mounted video display LVES, was engineered 20 years ago, various other devices have come and gone with a recent resurgence of the technology over the past few years. In this article, we discuss the history of the development of LVESs, describe the current state of available technology by outlining existing systems, and explore future innovation and research in this area. Although LVESs have now been around for more than two decades, there is still much that remains to be explored. With the growing popularity and availability of virtual reality and augmented reality technologies, we can now integrate these methods within low vision rehabilitation to conduct more research on customized contrast-enhancement strategies, image motion compensation, image-remapping strategies, and binocular disparity, all while incorporating eye-tracking capabilities. Future research should use this available technology and knowledge to learn more about the visual system in the low vision patient and extract this new information to create prescribable vision enhancement solutions for the visually impaired individual.
68Ga-PSMA Uptake in Angiolipoma
Authors: Dekker Irma , van der Leest Marloes , van Rijk Maartje C. , Gerritsen Winald R. , Arens Anne I. J.
Published: August 2018

68Ga-PSMA PET/CT is an imaging technique used in staging and detection of prostate cancer. However, enhanced uptake on 68Ga-PSMA PET/CT scan has also been ascribed to other malignant and benign lesions. We report on a case of a 56-year-old man with treated prostate carcinoma who had a 68Ga-PSMA PET/CT scan for restaging. 68Ga-PSMA uptakes in the prostatic bed and in multiple subcutaneous lesions were seen. Histopathology of a subcutaneous lesion revealed angiolipoma. It is important to be aware of the existence of the growing amount of reports on enhanced 68Ga-PSMA uptake unrelated to prostate cancer.
99mTc-Pertechnetate-SPECT/US Hybrid Imaging Enhances Diagnostic Certainty Compared With Conventional Thyroid Imaging With Scintigraphy and Ultrasound
Authors: Freesmeyer Martin , Winkens Thomas , Kuehnel Christian , Opfermann Thomas , Seifert Philipp
Published: August 2018

Evaluation of thyroid ultrasound and 99mTc-pertechnetate scintigraphy side by side frequently produces ambiguous results regarding the correct assignment of anatomy and functionality of a nodule. We describe the usefulness of 99mTc-pertechnetate-SPECT/US-fusion imaging. A 75-year-old woman was referred for exclusion of cold nodules. After conventional diagnostics (in vitro thyroid parameters, B mode–US, planar 99mTc-pertechnetate-thyroid scintigraphy), a SPECT was performed using a conventional gamma camera. The SPECT data set was transferred to an ultrasound device (LOGIQ E9), and sensor-navigated 3D ultrasound was performed. Both data sets (SPECT/US) were fused in real time, revealing the exact functional state of multiple nodules.
Value of 18F-FET PET in Patients With Suspected Tumefactive Demyelinating Disease—Preliminary Experience From a Retrospective Analysis
Authors: Barbagallo Massimo , Albatly Abdulrahman A. , Schreiner Simon , Hayward-Könnecke Helen K. , Buck Alfred , Kollias Spyros S. , Huellner Martin W.
Published: August 2018

Purpose

To investigate the diagnostic value of 18F-fluoroethyl-L-tyrosine (FET) positron emission tomography (PET) in patients with suspected tumefactive demyelinating disease.

Methods

We retrospectively examined FET-PET and MR imaging of 21 patients (12 female, 9 male) with known demyelinating disease and newly diagnosed tumefactive lesions. The maximum standardized uptake value (SUVmax), time activity curves (TAC) and lesion-to-background ratio (TBR) of these lesions were calculated. The standard of reference consisted of biopsy and/or follow-up imaging. FET parameters of true neoplastic lesions and tumefactive demyelinating lesions were compared using Mann-Whitney U-test and receiver operating characteristic (ROC) analysis.

Results

Nine patients (42.9%) had neoplastic lesions, 12 patients (57.1%) had tumefactive demyelinating lesions. TBRmax, SUVmax and TAC were significantly different between demyelinating lesions and neoplastic lesions: Tumors had a higher TBRmax (3.53 ± 1.09 vs. 1.48 ± 0.31, respectively; P < 0.001) and SUVmax (3.95 ± 1.59 vs. 1.86 ± 0.50, respectively; P < 0.001) than tumefactive demyelinating lesions. The TAC of tumors was significantly higher compared to tumefactive demyelinating lesions at all time points (P < 0.05). ROC analysis revealed that a TBRmax threshold of 2.2 and a SUVmax threshold of 2.5 could reliably differentiate tumor and tumefactive demyelination (area under the curve, 1.000 and 0.958, respectively).

Conclusion

In patients with demyelinating disease, FET-PET parameters TBRmax (cut-off 2.2) and SUVmax (cut-off 2.5) are able to distinguish tumefactive demyelinations from true neoplastic lesions.
Diagnostic 123I Whole Body Scan Prior to Ablation of Thyroid Remnant in Patients With Papillary Thyroid Cancer
Authors: Song Hong , Mosci Camila , Akatsu Haruko , Basina Marina , Dosiou Chrysoula , Iagaru Andrei
Published: August 2018

Objectives

The use of 123I whole body scintigraphy (WBS) before 131I radioiodine ablation (RIA) of the post-surgical thyroid remnant in patients with papillary thyroid cancer (PTC) remains debated. The American Thyroid Association’s guidelines state that WBS may be useful before RIA (rating C—expert opinion). Some institutions do not use 123I WBS before RIA in their routine clinical protocol. We were therefore prompted to evaluate the impact of 123I WBS prior to ablation of thyroid remnant in patients with PTC.

Methods

We reviewed data from 152 consecutive patients with PTC who had total thyroidectomy and were referred for RIA between August 2007 and February 2009 at our institution. The group included 107 women and 45 men, 13–82 years old (mean ± SD: 45.5 ± 18.3). Three endocrinologists blinded to the results of the 123I WBS reviewed patients’ data including sex, age, pathology, thyroglobulin (Tg) level, anti-Tg antibodies, thyroid stimulating hormone (TSH) level and ultrasound results. Each endocrinologist then returned a form with the recommended 131I dose for each participant, according to the following rules: 50–75 mCi (remnant ablation), 75–125 mCi (lymph nodes metastases), 150 mCi (lung metastases), and 200 mCi (bone metastases). We compared their recommended doses with the actual 131I doses prescribed after the pre-therapy 123I WBS.

Results

All three endocrinologists recommended the same dose in 98.7% of the cases. The dose prescribed by the endocrinologists matched the dose administered after analyzing the 123I WBS in 77 patients (51%). However, for 46 patients (30%) the endocrinologists would have given a lower dose, for 18 patients (12%) a higher dose than that administered based on the results of the 123I WBS, while 11 patients (7%) would have been treated unnecessarily (5/11 had no 123I uptake and 6/11 had 123I uptake in the breasts).

Conclusions

Our study suggests a significant role of the pre-therapy 123I WBS in PTC patients referred for 131I ablation post-thyroidectomy. The actual 131I dose that was administered based on the 123I WBS differed from the dose recommended in the absence of the 123I WBS in 49% of the cases.
Increased 18F-FDG Uptake in Lhermitte-Duclos Disease With Cowden Syndrome Revealed by PET-MRI
Authors: Piekarski Eve , Pyatigorskaya Nadya , Dormont Didier , Galanaud Damien , Kas Aurélie
Published: August 2018

A 62-year-old woman, with the history of breast and colorectal cancer, presented intermittent diplopia. A cerebellar lesion was revealed by 18F-FDG PET-MRI without post-gadolinium enhancement, but with increased perfusion and strong 18F-FDG uptake. The diagnosis of Cowden syndrome with PTEN gene mutation, linked to higher risk of neoplasia and occurrence of hamartomatous lesions characteristic of the Lhermitte-Duclos disease (LDD), was confirmed by genetic investigation.
The Pattern of Striatal Dopamine Depletion as a Prognostic Marker in De Novo Parkinson Disease
Authors: Chung Seok Jong , Yoo Han Soo , Lee Hye Sun , Oh Jungsu S. , Kim Jae Seung , Sohn Young H. , Lee Phil Hyu
Published: August 2018

Purpose

To investigate whether the patterns of striatal dopamine depletion could provide prognostic information on the clinical profiles of early-stage Parkinson disease (PD).

Methods

Approximately 634 patients with drug-naive PD who underwent 18F-FP-CIT PET scans were followed up for at least 2 years. After quantifying dopamine transporter (DAT) availability in each striatal subregion, the patterns of striatal dopamine depletion of each patient were assessed based on (1) the degree of dopamine loss in the other striatal subregions compared to the posterior putamen (inter-subregional ratio [ISR]) and (2) the interhemispheric asymmetry of dopamine loss in the posterior putamen (asymmetry index [AI]). According to their patterns, we assessed the longitudinal changes in l-dopa-equivalent doses and l-dopa-induced dyskinesia (LID)-free times using the linear mixed model and Cox regression model, respectively.

Results

There was no significant correlation between the ISR and AI values (Pearson correlation coefficient, 0.150). The linear mixed model showed that higher AI values were associated with slower longitudinal increases in l-dopa-equivalent dose across time (P = 0.003), whereas ISR values were not (P = 0.154). The Cox regression model demonstrated that higher ISR values were associated with early development of LID (hazard ratio, 1.693; P = 0.010), whereas AI values were not (P = 0.269).

Conclusions

The present study demonstrated that the pattern of anterior-to-posterior gradient and right-to-left asymmetry of striatal DAT availability predicted the development of LID and increasing doses of dopaminergic medications.
Predictive Value of FDG PET/CT to Detect Lymph Node Metastases in Cervical Cancer
Authors: Brunette Laurie L. , Bonyadlou Shahram , Ji Lingyun , Groshen Susan , Shuster Dena , Mehta Arjun , Sposto Richard , Matsuo Koji , Lin Yvonne G. , Roman Lynda D.
Published: August 2018

Purpose

The aim of this study was to determine the prognostic significance of PET/CT findings in women with cervical cancer and describe the normalization of lymph node SUVmax (nSUVmax).

Materials and Methods

A retrospective review was performed of 113 patients with cervical cancer who underwent a PET/CT before receiving definitive therapy. SUVmax measurements were normalized to the SUV of the pelvic blood pool. Patient, tumor, and PET/CT data were correlated to extracervical recurrence-free survival (ecRFS) and lymph node pathology.

Results

Of 113 patients, there were 23 (20%) extracervical recurrences. On univariate analysis, stage, histology, nSUVmax, and radiographic size of the primary tumor, and nSUVmax of the most hypermetabolic lymph node were significantly associated with ecRFS. On multivariable analysis, nSUVmax and radiographic size of the primary tumor remained associated with ecRFS (both P < 0.001). Sixty-six patients underwent pelvic, common iliac, and/or para-aortic nodal sampling. The sensitivity, specificity, false-negative, and false-positive rates of PET/CT for lymph node metastases were 53%, 75%, 6%, and 82%, respectively. On univariate analysis, nSUVmax, and radiographic size of the primary tumor, and nSUVmax of the most hypermetabolic lymph node, and radiographic size of the largest lymph node, were associated with the presence of at least one pathologically positive lymph node. On multivariable analysis, only the radiographic size of the largest lymph node remained significantly associated with lymph node metastases (P < 0.001).

Conclusions

The size and nSUVmax of the primary tumor were associated with ecRFS. PET/CT has a low false-negative rate but high false-positive rate for lymph node metastases.
Individual preventive social distancing during an epidemic may have negative population-level outcomes
Authors: Leung Ka Yin , Ball Frank , Sirl David , Britton Tom
Published: August 2018

The outbreak of an infectious disease in a human population can lead to individuals responding with preventive measures in an attempt to avoid getting infected. This leads to changes in contact patterns. However, as we show in this paper, rational behaviour at the individual level, such as social distancing from infectious contacts, may not always be beneficial for the population as a whole. We use epidemic network models to demonstrate the potential negative consequences at the population level. We take into account the social structure of the population through several network models. As the epidemic evolves, susceptible individuals may distance themselves from their infectious contacts. Some individuals replace their lost social connections by seeking new ties. If social distancing occurs at a high rate at the beginning of an epidemic, then this can prevent an outbreak from occurring. However, we show that moderate social distancing can worsen the disease outcome, both in the initial phase of an outbreak and the final epidemic size. Moreover, the same negative effect can arise in real-world networks. Our results suggest that one needs to be careful when targeting behavioural changes as they could potentially
worsen
the epidemic outcome. Furthermore, network structure crucially influences the way that individual-level measures impact the epidemic at the population level. These findings highlight the importance of careful analysis of preventive measures in epidemic models.
Repair and remodelling in the shells of the limpetPatella vulgata
Authors: O'Neill M. , Mala R. , Cafiso D. , Bignardi C. , Taylor D.
Published: August 2018

Limpets and other molluscs rely on shells to protect them from physical damage, predation, dehydration, etc. If the shell becomes damaged, this may significantly impair its function. In this work, experiments were carried out to investigate the effect of damage on the strength of shells of the common limpet (Patella vulgata) and their ability to repair this damage effectively. Shells were damaged in three ways: (i) low-energy impacts; (ii) abrasion of the outer layer; and (iii) creation of a small hole in the apex of the shell. Shells were left to repair for several time periods (0, 10, 30 and 60 days). The mechanical strength was evaluated by impacting the shells with a weight dropped from a known height. The damage reduced the strength (defined as impact energy to failure) by 50–70% depending on damage type. After 60 days, limpets in all three groups had repaired their shells significantly, bringing their strength to 79–91% of the control value (in each case, samples were statistically indistinguishable from their control counterparts). Measurements of the thickness of the shell at the apex suggest that the main effect of low-energy impact and abrasion is reduction in thickness, which correlates linearly with the impact energy needed for failure. The method of repair is believed to be by the growth of fresh shell material on the inside of the shell, though we could not identify this new material specifically. Even after 60 days, the shells were still statistically thinner than the controls. Consequently, there may be some other strengthening mechanism at work. This work has demonstrated the remarkable ability of limpets to detect the mechanical weakening of their shells caused by relatively subtle forms of damage and to take appropriate action to restore shell strength.
Designing stem cell niches for differentiation and self-renewal
Authors: Donnelly Hannah , Salmeron-Sanchez Manuel , Dalby Matthew J.
Published: August 2018

Mesenchymal stem cells, characterized by their ability to differentiate into skeletal tissues and self-renew, hold great promise for both regenerative medicine and novel therapeutic discovery. However, their regenerative capacity is retained only when in contact with their specialized microenvironment, termed thestem cell niche. Niches provide structural and functional cues that are both biochemical and biophysical, stem cells integrate this complex array of signals with intrinsic regulatory networks to meet physiological demands. Although, some of these regulatory mechanisms remain poorly understood or difficult to harness with traditional culture systems. Biomaterial strategies are being developed that aim to recapitulate stem cell niches, by engineering microenvironments with physiological-like niche properties that aim to elucidate stem cell-regulatory mechanisms, and to harness their regenerative capacityin vitro. In the future, engineered niches will prove important tools for both regenerative medicine and therapeutic discoveries.
Use of a powered ankle–foot prosthesis reduces the metabolic cost of uphill walking and improves leg work symmetry in people with transtibial amputations
Authors: Montgomery Jana R. , Grabowski Alena M.
Published: August 2018

People with transtibial amputations (TTAs) who use a powered ankle–foot prosthesis have equivalent metabolic costs and step-to-step transition work for level-ground walking over a range of speeds compared to non-amputees. The effects of using a powered compared to passive-elastic prosthesis for sloped walking are unknown. We sought to understand how the use of passive-elastic compared to powered ankle–foot prostheses affect metabolic cost and step-to-step transition work during sloped walking. Ten people (six M, four F) with TTAs walked 1.25 m s
−1
at 0°, ±3°, ±6° and ±9° using their own passive-elastic prosthesis and the BiOM powered ankle–foot prosthesis, while we measured metabolic rates, kinematics and kinetics. We calculated net metabolic power, individual leg step-to-step transition work and individual leg net work symmetry. The net metabolic power was 5% lower during walking on +3° and +6° uphill slopes when subjects used the BiOM compared to their passive-elastic prosthesis (
p
< 0.05). The use of the BiOM compared to a passive-elastic prosthesis did not affect individual leg step-to-step transition work (
p
> 0.05), but did improve individual leg net work symmetry on +6° and +9° uphill slopes (
p
< 0.01). People with TTAs who use a powered ankle–foot prosthesis have the potential to reduce metabolic costs and increase symmetry during walking on uphill slopes.
Generalized Erdős numbers for network analysis
Authors: Morrison Greg , Dudte Levi H. , Mahadevan L.
Published: August 2018

The identification of relationships in complex networks is critical in a variety of scientific contexts. This includes the identification of globally central nodes and analysing the importance of pairwise relationships between nodes. In this paper, we consider the concept of topological proximity (or ‘closeness’) between nodes in a weighted network using the generalized Erdős numbers (GENs). This measure satisfies a number of desirable properties for networks with nodes that share a finite resource. These include: (i) real-valuedness, (ii) non-locality and (iii) asymmetry. We show that they can be used to define a personalized measure of the importance of nodes in a network with a natural interpretation that leads to new methods to measure centrality. We show that the square of the leading eigenvector of an importance matrix defined using the GENs is strongly correlated with well-known measures such as PageRank, and define a personalized measure of centrality that is also well correlated with other existing measures. The utility of this measure of topological proximity is demonstrated by showing the asymmetries in both the dynamics of random walks and the mean infection time in epidemic spreading are better predicted by the topological definition of closeness provided by the GENs than they are by other measures.
Characteristics of biochar pellets from corn straw under different pyrolysis temperatures
Authors: Xing Xianjun , Fan Fangyu , Jiang Wen
Published: August 2018

Biomass resources have the potential to produce clean-energy. However, their physico-chemical properties are inferior to those of coal, and thus, biomass resources are not regarded as ideal feedstock for industrial application. In the present study, the pyrolysis of corn (maize) straw pellets was performed under different temperatures (400, 450, 500, 550 and 600°C) at a 10°C min
−1
heating rate and 30 min residence time, and the characteristics of biochar pellets were carefully investigated, particularly their elemental composition, hydrophobicity and mechanical resistance. Fourier transform infrared, proximate analysis and scanning electron microscopy were performed. Results indicated that the mass and energy yields of the biochar pellets decreased from 35.46 to 28.65% and from 50.17 to 45.52%, respectively, at increased temperature. Meanwhile, the higher heating value of the biochar pellets increased from 15.45 MJ kg
−1
in the raw materials to 21.86 and 24.55 MJ kg
−1
in the biochar produced at 400 and 600°C, respectively. In addition, biochar pellets showed good hydrophobicity, which benefited their storage and transportation, though mechanical resistance decreased. The pellets had compact structures, regular shapes and weakened or no functional groups in contrast with raw pellets, and these properties played important roles in the improvements.
Loss of miR-143 and miR-145 in condyloma acuminatum promotes cellular proliferation and inhibits apoptosis by targeting NRAS
Authors: Liu Xiaoyan , Zhang Yu , Wang Su , Liu Guoying , Ruan Liming
Published: August 2018

The expression profile of miRNAs and their function in condyloma acuminatum (CA) remains unknown. In this study, we aimed to detect the effects of miR-143 and miR-145, the most downregulated in CA samples using high-throughput sequencing, on cell proliferation and apoptosis, to determine a novel therapeutic target for CA recurrence. RT-qPCR was used to validate the lower expression of miR-143 and miR-145 in a larger size of CA samples, and the expression of NRAS in CA samples was significantly higher than self-controls as determined by western blotting assay. Luciferase assay was performed to confirm that miR-143 or miR-145 targeted NRAS directly. Transduction of LV-pre-miR-143 or LV-pre-miR-145 to human papilloma virus (HPV)-infected SiHa cells led to reduced proliferation, greater apoptosis and inhibition of expression of NRAS, PI3 K p110
α
and p-AKT. However, knockout of miR-143 or miR-145 in human epidermal keratinocytes by delivery of CRISPR/CAS9-gRNA for target miRNAs protected cells from apoptosis and upregulated expression of target genes as described above. MiR-143 and miR-145 sensitized cells to nutlin-3a, a p53 activator and MDM2 antagonist, while their loss protected cells from the stress of nutlin-3a. Furthermore, siRNA targeting NRAS showed similar effects on proliferation and apoptosis as miR-143 or miR-145. Taken together, our results suggest that loss of miR-143 or miR-145 in CA protects HPV-infected cells from apoptosis induced by environmental stress, in addition to promoting cellular proliferation and inhibiting apoptosis by targeting NRAS/PI3 K/ATK. Restoration of miR-143 or miR-145 might provide an applicable and novel approach to block the recurrence and progression of CA.
Algorithmically probable mutations reproduce aspects of evolution, such as convergence rate, genetic memory and modularity
Authors: Hernández-Orozco Santiago , Kiani Narsis A. , Zenil Hector
Published: August 2018

Natural selection explains how life has evolved over millions of years from more primitive forms. The speed at which this happens, however, has sometimes defied formal explanations when based on random (uniformly distributed) mutations. Here, we investigate the application of a simplicity bias based on a natural but algorithmic distribution of mutations (no recombination) in various examples, particularly binary matrices, in order to compare evolutionary convergence rates. Results both on synthetic and on small biological examples indicate an accelerated rate when mutations are not statistically uniform butalgorithmically uniform. We show that algorithmic distributions can evolve modularity and genetic memory by preservation of structures when they first occur sometimes leading to an accelerated production of diversity but also to population extinctions, possibly explaining naturally occurring phenomena such as diversity explosions (e.g. the Cambrian) and massive extinctions (e.g. the End Triassic) whose causes are currently a cause for debate. The natural approach introduced here appears to be a better approximation to biological evolution than models based exclusively upon random uniform mutations, and it also approaches a formal version of open-ended evolution based on previous formal results. These results validate some suggestions in the direction that computation may be an equally important driver of evolution. We also show that inducing the method on problems of optimization, such as genetic algorithms, has the potential to accelerate convergence of artificial evolutionary algorithms.
Adaptive evolution of synchronous egg-hatching in compensation for the loss of parental care
Authors: Jarrett Benjamin J. M. , Rebar Darren , Haynes Hannah B. , Leaf Miranda R. , Halliwell Chay , Kemp Rachel , Kilner Rebecca M.
Published: August 2018

Interactions among siblings are finely balanced between rivalry and cooperation, but the factors that tip the balance towards cooperation are incompletely understood. Previous observations of insect species suggest that (i) sibling cooperation is more likely when siblings hatch at the same time, and (ii) this is more common when parents provide little to no care. In this paper, we tested these ideas experimentally with the burying beetle,Nicrophorus vespilloides. Burying beetles convert the body of a small dead vertebrate into an edible nest for their larvae, and provision and guard their young after hatching. In our first experiment, we simulated synchronous or asynchronous hatching by adding larvae at different intervals to the carrion-breeding resource. We found that ‘synchronously’ hatched broods survived better than ‘asynchronously’ hatched broods, probably because ‘synchronous hatching’ generated larger teams of larvae, that together worked more effectively to penetrate the carrion nest and feed upon it. In our second experiment, we measured the synchronicity of hatching in experimental populations that had evolved for 22 generations without any post-hatching care, and control populations that had evolved in parallel with post-hatching care. We found that larvae were more likely to hatch earlier, and at the same time as their broodmates, in the experimental populations that evolved without post-hatching care. We suggest that synchronous hatching enables offspring to help each other when parents are not present to provide care. However, we also suggest that greater levels of cooperation among siblings cannot compensate fully for the loss of parental care.
Increased reproductive investment associated with greater survival and longevity in Cassin's auklets
Authors: Johns Michael E. , Warzybok Pete , Bradley Russell W. , Jahncke Jaime , Lindberg Mark , Breed Greg A.
Published: August 2018

Individuals increase lifetime reproductive output through a trade-off between investment in future survival and immediate reproductive success. This pattern may be obscured in certain higher quality individuals that possess greater reproductive potential. The Cassin's auklet (Ptychoramphus aleuticus) is a long-lived species where some individuals exhibit greater reproductive ability through a behaviour called double brooding. Here, we analyse 32 years of breeding histories from marked known-age auklets to test whether double brooding increases lifetime fitness despite the increased mortality and reduced lifespan higher reproductive effort would be expected to incur. Multistate mark–recapture modelling revealed that double brooding was strongly positively associated with higher annual survival and longevity. The mean (95% confidence interval) apparent survival was 0.69 (0.21, 0.91) for individuals that executed a single brood and 0.96 (0.84, 0.99) for those that double-brooded. Generalized linear mixed models indicated individuals that attempted multiple double broods over their lifetime were able to produce on average seven times as many chicks and live nearly 6 years longer than birds that never attempted a double brood. We found that high-quality individuals exhibited both increased reproductive effort and longevity, where heterogeneity in individual quality masked expected life-history trade-offs.