bluuebunny/crossref_metadata_2025 huggingface dataset:
At-Risk Tackling Techniques in American Football
Authors: Stockwell David W. , Blalock Richard , Podell Kenneth , Marco Rex A.W.
Published: February 2020

Background:

In American football, fewer fatalities and severe injuries have been seen annually since 1976, after data from 1971 through 1975 were retrospectively reviewed to better understand the mechanisms involved in catastrophic cervical spine injury and rules were enacted to prohibit certain types of aggressive tackling. The National Football Head and Neck Injury Registry was established in 1975.

Purpose:

To assess (1) tackling techniques that coaches were teaching at 3 levels—youth level (YL; 4th to 5th grades), middle school (MS; 6th to 8th grades), and high school (HS; 9th to 12th grades); (2) tackling techniques used during games; and (3) the successful tackle rates of these techniques.

Study Design:

Descriptive epidemiology study.

Methods:

Surveys were distributed via email to 500 coaches of YL, MS, and HS football teams in Texas. Coaches provided video recordings of football games, and all tackle attempts were graded by a single reviewer who watched game videos; 1000 consecutive tackles were observed for each group. Survey data included how coaches instructed their players to tackle, the types of tackles, the number of tackles versus missed tackles, the head position, and the initial contact. Data were analyzed with the chi-square test. A subset of 100 consecutive tackles at each level of play was reviewed by 2 blinded reviewers to assess intra- and interrater reliabilities.

Results:

In all groups, coaches responded that they preferred to teach the at-risk “head across the bow” tackling technique (83% YL, 81% MS, 75% HS). Coaches stated that they instructed players to “keep your head up,” as currently recommended, 89% in YL, 100% in MS, and 81% in HS. During games, players used head-up, inside-shoulder tackles more successfully across all groups (97.5% YL, 99.5% MS, 98.8% HS). While intra- and interrater reliabilities were in the good range, these scores were lower in the youth group.

Conclusion:

Our study supports the effectiveness of tackling with the head up and making the initial contact with the inside shoulder. Lower reliability ratings for the youth group were likely due to lower video quality and the lack of players’ tackling experience.
Are patients willing to accept longer travel times to decrease their risk associated with surgical procedures? A systematic review
Authors: Bühn Stefanie , Holstiege Jakob , Pieper Dawid
Published: February 2020

Background

Distance to a hospital is an influencing factor for patients´ decision making when choosing a hospital for surgery. It is unclear whether patients prefer to travel further to regional instead of local hospitals if the risk associated with elective surgery is lower in the farther hospital. The aim of our systematic review was to investigate patient preferences for the location of care, taking into consideration surgical outcomes and hospital distance.

Methods

MEDLINE (PubMed), EconLit, PsycInfo and EMBASE were searched until November 2019. We included experimental choice studies in which participants were asked to make a hypothetical decision where to go for elective surgery when surgical risk and/or distance to the hospitals vary. There was no restriction on the type of intervention or study. Reviewers independently extracted data using a standardized form. The number and proportion of participants willing to accept additional risk to obtain surgery in the local hospital was recorded. We also extracted factors associated with the decision.

Results

Five studies exploring participants´ preferences for local care were included. In all studies, there were participants who, independently of a decreased mortality risk or a higher survival benefit in the regional hospital, adhered to the local hospital. The majority of the patients were willing to travel longer to lower their surgical risk. Older age and fewer years of formal education were associated with a higher risk tolerance in the local hospital.

Conclusions

Whether patients were willing to travel for a lower surgery-associated risk could not be answered in a straightforward manner. The studies we identified showed that decision making also relies on factors other than on rational information on risk or distance to hospital.

Trial registration

International prospective register of ongoing systematic reviews (PROSPERO): CRD42016033655. Registered 1 January 2016.
Using text mining and sentiment analysis to analyse YouTube Italian videos concerning vaccination
Authors: Porreca Annamaria , Scozzari Francesca , Di Nicola Marta
Published: February 2020

Background

Recently, social networks have become a popular source of information on health topics. Particularly, in Italy, there is a lively discussion on the web regarding vaccines also because there is low vaccination coverage, vaccines hesitancy, and anti-vaccine movements. For these reasons, in 2017, Institutions have introduced a law to force children to make ten compulsory vaccines for school attendance and proposed a vaccination campaign. On social networks, this law has fostered a fierce discussion between pro-vaccinations and anti-vaccinations people. This paper aims to understand if and how the population’s opinion has changed before the law and after the vaccination campaign using the titles of the videos uploaded on Youtube in these periods.

Method

Using co-occurrence network (CON) and sentiment analysis, we analysed the topics of YouTube Italian videos on vaccines in 2017 and 2018.

Results

The CON confirms that vaccinations were very disapproved before the law. Instead, after the communication campaign, people start to be less critical. The sentiment analysis shows that the intense vaccination campaign also promoted by medical doctors pushed the sentiment to change polarity from a prevailing negative opinion in 2017 (52% negative) to a positive one in 2018 (54% positive).

Conclusion

At the population level, the potential misinformation of social networks could be significant and is a real risk for health. Our study highlights that vaccination campaigns on social networks could be an essential instrument of health policies and a sharp weapon to fight ignorance and misrepresentations of non-qualified people influencing individuals’ decision-making.
Using the 12-item short form health survey (SF-12) to assess self rated health of an engaged population impacted by hurricane Harvey, Houston, TX
Authors: Sansom Garett T. , Kirsch Katie , Horney Jennifer A.
Published: February 2020

Background

In the last decade there has been an increase in community-based organizations providing support and educational outreach to populations effected by hazards. Prior research has demonstrated various roles that community social capital can play in both the enhancement of disaster preparedness and the mitigation of physical and mental health impacts following a natural disaster.

Methods

To assess self-reported health of residents of South Houston, Texas impacted by Hurricane Harvey, attendees of a community event completed a survey that included the 12 item short form health survey version 2 (SF-12v2).

Results

Although survey participants were older and more likely to be African-American than the overall population of Houston, they had higher mental health composite scores that the national average, with increases in mental wellbeing associated with a longer length of residence in their neighborhood.

Conclusions

The City of Houston, with highly segregated, socially vulnerable populations at high risk from natural hazards, should consider ways to support community engagement around disaster preparedness, response, and recovery that may build community cohesion and improve post-disaster mental health.
Correlation between clinical parameters of crown and gingival morphology of anterior teeth and periodontal biotypes
Authors: Yin Xiao-jie , Wei Bang-yan , Ke Xiu-ping , Zhang Ting , Jiang Meng-yang , Luo Xia-yan , Sun Hui-qiang
Published: February 2020

Background

In this study, we conducted a quantitative analysis of the clinical parameters of crown and gingival morphology (CGM) of the maxillary anterior teeth (MAT). We also analyzed the correlation of these parameters with periodontal biotype (PB), with a view to providing objective standards for PB diagnosis.

Methods

The three-dimensional (3D) maxillary digital models of 56 individuals were obtained using an intra-oral scanner. The following parameters were measured with the SpaceClaim software: gingival angle (GA), papilla width (PW), papilla height (PH), crown length (CL), crown width (CW), crown width/crown length ratio (CW/CL), bucco-lingual width of the crown (BLW), contact surface width (CSW), and contact surface height/crown length ratio (CS/CL). The PB were determined based on the transparency of the periodontal probe through the gingival sulcus. Independent factors influencing PB were analyzed by logistic regression, and the optimal cutoff values for the independent influencing factors were analyzed using receiver operating characteristic curves (ROC curves).

Results

There was no significant difference in the parameters of CGM of the MAT at the left and right sides. The thick biotype accounted for 69.6%, and the parameters of GA, PW, PH, CW, CW/CL and CS/CL were significantly correlated with PB (P ≤ 0.2). GA (odds ratio (OR) = 1.206) and PW (OR = 5.048) were identified as independent predictive factors of PB, with areas under the ROC curve (AUC) of 0.807 and 0.881, respectively, and optimal cutoff values of 95.95° and 10.01 mm, respectively.

Conclusion

The CGMs of the MAT at the left and right side are symmetrical. The thin biotype accounts for a small proportion, and GA and PW are independent influencing factors of PB. GA of 95.95° and PW of 10.01 mm are the optimal cutoff values for categorization of individuals as thick biotype. This indicates that when the GA and PW of the right maxillary central incisor are G ≥ 95.95° and ≥ 10.01 mm, respectively, there is a higher probability that these individuals will be categorized as thick biotype.
The tanning hormone, bursicon, does not act directly on the epidermis to tan the Drosophila exoskeleton
Authors: Flaven-Pouchon Justin , Alvarez Javier V. , Rojas Candy , Ewer John
Published: February 2020

Background

In insects, continuous growth requires the periodic replacement of the exoskeleton. Once the remains of the exoskeleton from the previous stage have been shed during ecdysis, the new one is rapidly sclerotized (hardened) and melanized (pigmented), a process collectively known as tanning. The rapid tanning that occurs after ecdysis is critical for insect survival, as it reduces desiccation, and gives the exoskeleton the rigidity needed to support the internal organs and to provide a solid anchor for the muscles. This rapid postecdysial tanning is triggered by the “tanning hormone”, bursicon. Since bursicon is released into the hemolymph, it has naturally been assumed that it would act on the epidermal cells to cause the tanning of the overlying exoskeleton.

Results

Here we investigated the site of bursicon action inDrosophilaby examining the consequences on tanning of disabling the bursicon receptor (encoded by thericketsgene) in different tissues. To our surprise, we found that rapid tanning does not requirericketsfunction in the epidermis but requires it instead in peptidergic neurons of the ventral nervous system (VNS). Although we were unable to identify the signal that is transmitted from the VNS to the epidermis, we show that neurons that express theDrosophilainsulin-like peptide ILP7, but not the ILP7 peptide itself, are involved. In addition, we found that some of the bursicon targets involved in melanization are different from those that cause sclerotization.

Conclusions

Our findings show that bursicon does not act directly on the epidermis to cause the tanning of the overlying exoskeleton but instead requires an intermediary messenger produced by peptidergic neurons within the central nervous system. Thus, this work has uncovered an unexpected layer of control in a process that is critical for insect survival, which will significantly alter the direction of future research aimed at understanding how rapid postecdysial tanning occurs.
Mediating role of occupational stress and job satisfaction on the relationship between neuroticism and quality of life among Chinese civil servants: a structural equation model
Authors: Kong Wenwen , Yang Yaoyao , Zhang Feng , Wang Hui , Feng Danjun
Published: February 2020

Background

Knowledge on the quality of life (QOL) of civil servants is limited. Therefore, the aims of this study were to investigate the QOL of civil servants, and examine whether occupational stress and job satisfaction mediated the association between neuroticism and QOL in civil servants from Shandong, China.

Methods

The cross-sectional study included 559 civil servants aged 27 to 60 years from Shandong province in China. Participants completed questionnaires assessing neuroticism, occupational stress, job satisfaction, and QOL. Structural equation modeling (SEM) was conducted to examine the hypothetical model.

Results

Among the civil servants, the average score for QOL was 75.49 ± 14.73. The SEM analysis showed a good fit of the data to the hypothesized model. Neuroticism, occupational stress, and job satisfaction explained 38% of the variance of QOL. Neuroticism was positively correlated with occupational stress and negatively correlated with job satisfaction and QOL. A strong direct effect (− 0.386,P < 0.01) and moderate indirect effect (− 0.133,P < 0.01) of neuroticism on QOL mediated by occupational stress and job satisfaction were observed. In addition, a direct effect (− 0.197,P < 0.01) and an indirect effect (− 0.044,P < 0.01) of occupational stress on QOL mediated by job satisfaction were also observed.

Conclusions

Occupational stress and job satisfaction partly mediated the relationship between neuroticism and QOL among Chinese civil servants. Thus, selecting individuals with a low level of neuroticism as civil servants, reducing occupational stress, and increasing job satisfaction may be important measures to improve their QOL.
The exoskeleton expansion: improving walking and running economy
Authors: Sawicki Gregory S. , Beck Owen N. , Kang Inseung , Young Aaron J.
Published: February 2020

Since the early 2000s, researchers have been trying to develop lower-limb exoskeletons that augment human mobility by reducing the metabolic cost of walking and running versus without a device. In 2013, researchers finally broke this ‘metabolic cost barrier’. We analyzed the literature through December 2019, and identified 23 studies that demonstrate exoskeleton designs that improved human walking and running economy beyond capable without a device. Here, we reviewed these studies and highlighted key innovations and techniques that enabled these devices to surpass the metabolic cost barrier and steadily improve user walking and running economy from 2013 to nearly 2020. These studies include, physiologically-informed targeting of lower-limb joints; use of off-board actuators to rapidly prototype exoskeleton controllers; mechatronic designs of both active and passive systems; and a renewed focus on human-exoskeleton interface design. Lastly, we highlight emerging trends that we anticipate will further augment wearable-device performance and pose the next grand challenges facing exoskeleton technology for augmenting human mobility.
Analysis of risk factors for complications after femoral neck fracture in pediatric patients
Authors: Dai Zhen-Zhen , Zhang Zhi-Qiang , Ding Jing , Wu Zhen-Kai , Yang Xuan , Zhang Zi-Ming , Li Hai
Published: February 2020

Background

Pediatric femoral neck fracture is a rare injury but yields frequent complications. However, there is a paucity of data regarding the risk factors for these complications.

Purpose

The present article reports the rate of complications after femoral neck fracture in pediatric patients and investigates the possible risk factors.

Methods

We retrospectively reviewed 44 children (mean age of 9.0 years, range from 2 to 14 years) who were surgically treated for femoral neck fracture in a single trauma center with a mean follow-up of 57.75 months (range from 11 to 224 months). Related clinical factors were recorded and analyzed by multivariable logistic regression.

Results

Fracture displacement or Delbet-type fracture had no relation to the injury mechanism. However, younger children experienced severe trauma, combined injury, and low fracture location more than older individuals did. Children with combined injuries were more likely to have a longer waiting time for surgical reduction. Common complications included avascular necrosis (AVN) in 14 cases, nonunion of fracture in 2 cases, coxa vara in 4 cases, and premature physeal closure (PPC) in 7 cases. Only the Delbet type was an independent predictor of AVN (OR = 0.14, p = 0.030). Inadequate reduction was associated with higher rates of coxa vara (OR = 33.19, p = 0.032). Epiphysis penetration in children younger than 10 years old increased the rate of PPC (p = 0.032). No significant risk factor was found for fracture nonunion.

Conclusion

For femoral neck fracture in pediatric patients, both the injury mechanism and fracture characteristics have age-related distributions. Early reduction should be carried out as early as possible based on the safe condition of the child, but for younger children, transepiphyseal fixation should be avoided. AVN may be intrinsic to injury characteristics rather than resulting from the choice of treatment mode.
Examining the benefits and harms of Alzheimer’s disease screening for family members of older adults: study protocol for a randomized controlled trial
Authors: Fowler Nicole R. , Head Katharine J. , Perkins Anthony J. , Gao Sujuan , Callahan Christopher M. , Bakas Tamilyn , Suarez Shelley D. , Boustani Malaz A.
Published: February 2020

Background

Multiple national expert panels have identified early detection of Alzheimer’s disease and related dementias (ADRD) as a national priority. However, the United States Preventive Services Task Force (USPSTF) does not currently support screening for ADRD in primary care given that the risks and benefits are unknown. The USPSTF stresses the need for research examining the impact of ADRD screening on family caregiver outcomes.

Methods

The Caregiver Outcomes of Alzheimer’s Disease Screening (COADS) is a randomized controlled trial that will examine the potential benefits or harms of ADRD screening on family caregivers. It will also compare the effectiveness of two strategies for diagnostic evaluation and management after ADRD screening. COADS will enroll 1800 dyads who will be randomized into three groups (n = 600/group): the ‘Screening Only’ group will receive ADRD screening at baseline and disclosure of the screening results, with positive-screen participants receiving a list of local resources for diagnostic follow-up; the ‘Screening Plus’ group will receive ADRD screening at baseline coupled with disclosure of the screening results, with positive-screen participants referred to a dementia collaborative care program for diagnostic evaluation and potential care; and the control group will receive no screening. The COADS trial will measure the quality of life of the family member (the primary outcome) and family member mood, anxiety, preparedness and self-efficacy (the secondary outcomes) at baseline and at 6, 12, 18 and 24 months. Additionally, the trial will examine the congruence of depressive and anxiety symptoms between older adults and family members at 6, 12, 18 and 24 months and compare the effectiveness of two strategies for diagnostic evaluation and management after ADRD screening between the two groups randomized to screening (Screening Only versus Screening Plus).

Discussion

We hypothesize that caregivers in the screening arms will express higher levels of health-related quality of life, lower depressive and anxiety symptoms, and better preparation for caregiving with higher self-efficacy at 24 months. Results from this study will directly inform the National Plan to Address Alzheimer’s Disease, the USPSTF and other organizations regarding ADRD screening and early detection policies.

Trial registration

ClinicalTrials.gov, NCT03300180. Registered on 3 October.
A simple strategy based on fibers coated with surfactant-functionalized multiwalled carbon nanotubes to improve the properties of solid-phase microextraction of phenols in aqueous solution
Authors: Zhou Xueqing , Xie Yanli , Zhao Zhendong , Fu Wenyan
Published: February 2020

Methods and experiments

In this study, a functionalized multiwalled carbon nanotube (MWCNT)-coated solid-phase microextraction (SPME) fiber was developed for concentrating analytes in aqueous samples. Sodium deoxycholate (NaDC) was used as a dispersing agent for non-covalent modification of MWCNTs. The coating showed porous structure and large adsorption capacity. To investigate the capability of this MWCNTs/NaDC SPME fiber, it was applied to the analysis of phenols in aqueous solution. After extraction, the analytes were desorbed in an acetonitrile–water solution and analyzed using high-performance liquid chromatography.

Results

The MWCNTs/NaDC fiber exhibited good analytical performance, and fine preparation reproducibility was obtained with the relative standard deviations (RSDs) ranging from 4.9% to 10.2% (n = 6) in one batch, from 5.7% to 11.9% (n = 3) among different batches. Under the optimum extraction conditions, the detection limits were 0.15–0.30 ng/mL(S/N = 3), the linear detection ranges were 1–100 ng/mL (R2 ≥ 0.9997) for these analytes, and good recoveries (80.3–95.4%) were obtained for the spiked samples.

Conclusion

This is a simple and accurate pretreatment method for the analysis of phenols in aqueous samples.
Maternal diabetes and obesity influence the fetal epigenome in a largely Hispanic population
Authors: Rizzo Heather E. , Escaname Elia N. , Alana Nicholas B. , Lavender Elizabeth , Gelfond Jonathan , Fernandez Roman , Hibbs Matthew A. , King Jonathan M. , Carr Nicholas R. , Blanco Cynthia L.
Published: February 2020

Background

Obesity and diabetes mellitus are directly implicated in many adverse health consequences in adults as well as in the offspring of obese and diabetic mothers. Hispanic Americans are particularly at risk for obesity, diabetes, and end-stage renal disease. Maternal obesity and/or diabetes through prenatal programming may alter the fetal epigenome increasing the risk of metabolic disease in their offspring. The aims of this study were to determine if maternal obesity or diabetes mellitus during pregnancy results in a change in infant methylation of CpG islands adjacent to targeted genes specific for obesity or diabetes disease pathways in a largely Hispanic population.

Methods

Methylation levels in the cord blood of 69 newborns were determined using the Illumina Infinium MethylationEPIC BeadChip. Over 850,000 different probe sites were analyzed to determine whether maternal obesity and/or diabetes mellitus directly attributed to differential methylation; epigenome-wide and regional analyses were performed for significant CpG sites.

Results

Following quality control, agranular leukocyte samples from 69 newborns (23 normal term (NT), 14 diabetes (DM), 23 obese (OB), 9 DM/OB) were analyzed for over 850,000 different probe sites. Contrasts between the NT, DM, OB, and DM/OB were considered. After correction for multiple testing, 15 CpGs showed differential methylation from the NT, associated with 10 differentially methylated genes between the diabetic and non-diabetic subgroups, CCDC110, KALRN, PAG1, GNRH1, SLC2A9, CSRP2BP, HIVEP1, RALGDS, DHX37, and SCNN1D. The effects of diabetes were partly mediated by the altered methylation of HOOK2, LCE3C, and TMEM63B. The effects of obesity were partly mediated by the differential methylation of LTF and DUSP22.

Conclusions

The presented data highlights the associated altered methylation patterns potentially mediated by maternal diabetes and/or obesity. Larger studies are warranted to investigate the role of both the identified differentially methylated loci and the effects on newborn body composition and future health risk factors for metabolic disease. Additional future consideration should be targeted to the role of Hispanic inheritance. Potential future targeting of transgenerational propagation and developmental programming may reduce population obesity and diabetes risk.
Strong laws for weighted sums of random variables satisfying generalized Rosenthal type inequalities
Authors: Yi Yanchun , Chen Pingyan , Sung Soo Hak
Published: February 2020

Let $1\le p<2$1≤p<2 and $0<\alpha , \beta <\infty $0<α,β<∞ with $1/p=1/\alpha +1/\beta $1/p=1/α+1/β. Let $\{X_{n}, n\ge 1\}${Xn,n≥1} be a sequence of random variables satisfying a generalized Rosenthal type inequality and stochastically dominated by a random variable X with $E|X|^{\beta }< \infty $E|X|β<∞. Let $\{a_{nk}, 1\le k\le n, n\ge 1\}${ank,1≤k≤n,n≥1} be an array of constants satisfying $\sum_{k=1}^{n} |a_{nk}|^{\alpha }=O(n)$∑k=1n|ank|α=O(n). Marcinkiewicz–Zygmund type strong laws for weighted sums of the random variables are established. Our results generalize or improve the corresponding ones of Wu (J. Inequal. Appl. 2010:383805, 2010), Huang et al. (J. Math. Inequal. 8:465–473, 2014), and Wu et al. (Test 27:379–406, 2018).
Global carbon surcharge for the reduction of anthropogenic emission of carbon dioxide
Authors: Thess André , Klein Martin , Nienhaus Kristina , Pregger Thomas
Published: February 2020

Background

Many governments take the view that voluntary national targets to reduce greenhouse gas emissions are sufficient to avoid negative climate effects. In the absence of independent verification, however, pledges are unlikely to be sufficient for a rapid and strong reduction of emissions. It is often claimed that a global carbon tax could be an effective instrument. However, such a tax is difficult to set and to collect, especially in countries with poor administrative infrastructure.

Results

Here, we formulate and discuss a novel approach, the Global Carbon Surcharge (GCS), that mimics a carbon tax but does not require tax collection by governments. We define GCS as a requirement or a voluntary commitment encompassing all companies extracting carbon-carrying raw materials, namely coal, oil, gas and limestone, with the aim to burden their extraction with costs proportional to their carbon intensity. GCS mandates all companies to store these materials immediately after mining for a given period of time in the vicinity of the production site. Thereby, GCS generates additional costs that propagate through all sectors of the global economy. We elucidate how the investment costs for the storage infrastructure translate into surcharges on the raw materials.

Conclusions

We show that by a proper choice of the storage time and the size of the storage unit, GCS becomes equivalent to a carbon tax in the range between 50 and 100 € per ton of CO2 that is assumed to be necessary for the transition to a carbon-neutral energy system. An attractive feature of GCS is that it can be verified, in particular by citizens themselves, using publicly available satellite data. Finally, if compulsory storage is coupled to blockchain-based smart contracts and a mandatory (expensive) mining of cryptocurrency, GCS can be operated without governmental protectionism, corruption and fraud. However, the main uncertainties of the GCS approach lie in the substantial expansion of infrastructure and the fact that the induced price effects must be sufficient to achieve a rapid and far-reaching substitution of fossil fuels.
Race modifies default mode connectivity in Alzheimer’s disease
Authors: Misiura Maria B. , Howell J. Christina , Wu Junjie , Qiu Deqiang , Parker Monica W. , Turner Jessica A. , Hu William T.
Published: February 2020

Background

Older African Americans are more likely to develop Alzheimer’s disease (AD) than older Caucasians, and this difference cannot be readily explained by cerebrovascular and socioeconomic factors alone. We previously showed that mild cognitive impairment and AD dementia were associated with attenuated increases in the cerebrospinal fluid (CSF) levels of total and phosphorylated tau in African Americans compared to Caucasians, even though there was no difference in beta-amyloid 1–42 level between the two races.

Methods

We extended our work by analyzing early functional magnetic resonance imaging (fMRI) biomarkers of the default mode network in older African Americans and Caucasians. We calculated connectivity between nodes of the regions belonging to the various default mode network subsystems and correlated these imaging biomarkers with non-imaging biomarkers implicated in AD (CSF amyloid, total tau, and cognitive performance).

Results

We found that race modifies the relationship between functional connectivity of default mode network subsystems and cognitive performance, tau, and amyloid levels.

Conclusion

These findings provide further support that race modifies the AD phenotypes downstream from cerebral amyloid deposition, and identifies key inter-subsystem connections for deep imaging and neuropathologic characterization.
Comparative evaluation among laser-treated, machined, and sandblasted/acid-etched implant surfaces: an in vivo histologic analysis on sheep
Authors: De Tullio I. , Berardini M. , Di Iorio D. , Perfetti F. , Perfetti G.
Published: February 2020

Purpose

The aim of the present in vivo analysis was to evaluate the osseointegration process of titanium implants with three different surfaces (machined, sandblasted and acid-etched, and laser-treated) after 15 and 30 days of healing period.

Materials and methods

Thirty-six implants with different surfaces were placed in the iliac crest of four Bergamasca sheep. The implant surfaces tested were sandblasted and acid-etched (group A), laser-treated (group B), and fully machined (group C). Two animals were sacrificed after 15 days while the other two after 30 days. Histological and histomorphometric analyses were performed.

Results

After 30 days, the bone tissue layer onto implant groups A and B appeared almost continuous with small marrow spaces interruption, while on the machined surface (group C), larger spaces with marrow tissue alternated with the bony trabeculae onto the titanium surface. Implants in groups A and B showed significantly higher implant contact percentage (BIC%) value than group C (P < 0.05). Moreover, it was observed a BIC% increase in both groups A and B between 15 and 30 days while in the machined group (group C), the BIC% decreased.

Conclusion

Results from the present in vivo analysis revealed that both sandblasted/acid-etched and laser-treated titanium implants, compared to the machined ones, have higher values of osseointegration in less healing time.
Feasibility of procedures for a randomised pilot study of reduced exertion, high-intensity interval training (REHIT) with non-diabetic hyperglycaemia patients
Authors: Haines Matthew
Published: February 2020

Background

Physical activity and exercise interventions to improve health frequently bring about intended effects under ideal circumstances but often fail to demonstrate benefits in real-world contexts. The aim of this study was to describe the feasibility of an exercise intervention (reduced-exertion, high-intensity interval training) in non-diabetic hyperglycaemia patients delivered in a National Health Service setting to assess whether it would be appropriate to progress to a future large-scale study.

Methods

The intention was to recruit 40 participants from a single centre (specialist diabesity centre). Patients were eligible to take part if they were diagnostically defined as non-diabetic hyperglycaemic based on a glycated haemoglobin (HbA1c) value of 42–46 mmol mol. Study procedures including recruitment, occurrence of adverse events, intervention acceptability, and intervention adherence were used to assess feasibility.

Results

Key criteria for progression to a larger study were not met. The study revealed several issues including patient eligibility, challenges to recruitment, patient consent, and poor clinician engagement. Furthermore, despite the simplicity and convenience of using HbA1cto screen for diabetes risk, the process of accurately screening and case finding eligible patients was problematic. The small sample recruited for this trial (n= 6) also limits the interpretation of data, thus it is not possible to estimate the variability of intended outcomes to use in a formal sample size calculation for a full-scale trial. Some aspects of the intervention worked well. The acceptability of the exercise intervention and outcome measures met progression criteria thresholds and adherence was very high, with 97% of exercise sessions completed for participants that finished the study.

Conclusions

Given the issues, the trial is not feasible in its current form. Yet, this preparatory stage of trial design pre-empted problems with the intervention that could be changed to optimise the design and conduct of future studies. Solutions to the issues identified in this study revolve around using a dedicated local recruiter with a strong relationship among the healthcare team and patients, using participant incentives to take part, and allowing for a longer recruitment period.

Trial registration

ClinicalTrials.gov,NCT04011397. Registered 07 July 2019—retrospectively registered.
Normative data for two challenging tests of face matching under ecological conditions
Authors: Stacchi Lisa , Huguenin-Elie Eva , Caldara Roberto , Ramon Meike
Published: February 2020

Background

Unfamiliar face processing is an ability that varies considerably between individuals. Numerous studies have aimed to identify its underlying determinants using controlled experimental procedures. While such tests can isolate variables that influence face processing, they usually involve somewhat unrealistic situations and optimized face images as stimulus material. As a consequence, the extent to which the performance observed under laboratory settings is informative for predicting real-life proficiency remains unclear.

Results

We present normative data for two ecologically valid but underused tests of face matching: the Yearbook Test (YBT) and the Facial Identity Card Sorting Test (FICST). The YBT (n = 252) measures identity matching across substantial age-related changes in facial appearance, while the FICST (n = 218) assesses the ability to process unfamiliar facial identity despite superficial image variations. To determine the predictive value of both tests, a subsample of our cohort (n = 181) also completed a commonly used test of face recognition and two tests of face perception (the long form of the Cambridge Face Memory Test (CFMT+), the Expertise in Facial Comparison Test (EFCT) and the Person Identification Challenge Test (PICT)).

Conclusions

Focusing on the top performers identified independently per test, we made two important observations: 1) YBT and FICST performance can predict CFMT+ scores and vice versa; and 2) EFCT and PICT scores neither reliably predict superior performance in ecologically meaningful and challenging tests of face matching, nor in the most commonly used test of face recognition. These findings emphasize the necessity for using challenging and ecologically relevant, and thus highly sensitive, tasks of unfamiliar face processing to identify high-performing individuals in the normal population.
Analysis of prevalence and prognostic implications of early versus delayed PSA declines during radium-223 (Ra223) treatment among men with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Sidhu Amanjot , Zalewski Pawel , Kapoor Anil , Fleshner Neil , Chow Edward , Emmenegger Urban
Published: February 2020

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Background: Ra233 is a well-tolerated, bone-seeking alpha emitter that prolongs the survival of men with mCRPC. Since there is a lack of validated biomarkers useful for disease monitoring during Ra223 therapy, we sought to characterize prostate-specific antigen (PSA) response patterns within a retrospective cohort study of real-world Ra223 treatment in four cancer centres across Ontario. Methods: Of 198 patients (pts) overall, 64 were not included due to incomplete data. The remaining 134 pts were grouped into (i) early PSA responders with a ≥30% PSA decrease (PSA30) within 12 weeks of treatment start, (ii) pts with an initial PSA flare followed by decreasing PSA, and (iii) non-responders. We analyzed the overall survival (OS) of these three cohorts using the Kaplan-Meier method and log-rank testing. Results: PSA30 responses were rare (n = 11; 8.2%), PSA flares were seen in 20.2% of pts (n = 27), but the majority of pts did not achieve a PSA response (n = 96; 71.7%). Of the pts identified as having a PSA flare, 11/27 (40.7%) presented with a post-flare PSA decrease below baseline, whereas in 16/27 (59.3%) the PSA decreased below the flare peak but not below baseline. 5/27 (18.5%) pts with a PSA flare achieved a PSA30. The median OS was not reached, 15.8 months and 14.7 months in responders, flare pts and non-responders, respectively (p > 0.05). Similarly, one year OS was 90.9%, 67.7% and 63.9% in responders, flare pts and non-responders. Conclusions: PSA flares are seen in one fifth of men undergoing Ra223 therapy for mCRPC. Despite delayed PSA declines of varying degrees, the survival of PSA flare pts is comparable to men without any PSA decline.
TALAPRO-1: A phase II study of talazoparib (TALA) in men with DNA damage repair mutations (DDRmut) and metastatic castration-resistant prostate cancer (mCRPC)—First interim analysis (IA).
Authors: De Bono Johann S. , Mehra Niven , Higano Celestia S. , Saad Fred , Buttigliero Consuelo , Mata Marielena , Chen Hsiang-Chun , Healy Cynthia G. , Paccagnella M. Luisa , Czibere Akos , Fizazi Karim
Published: February 2020

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Background: Phase 2 and 3 studies with poly(ADP-ribose) polymerase inhibitors (PARPi) have demonstrated antitumor activity in patients (pts) with mCRPC with DDRmut who were previously treated with novel hormonal therapy (NHT). We report the first IA of a Phase 2 study of TALA, a potent inhibitor and trapper of PARP. Methods: TALAPRO-1 (NCT03148795) is enrolling pts (N ≈ 100) with measurable soft tissue disease, progressive mCRPC, and DDRmut likely to sensitize to PARPi (including ATM, ATR, BRCA1, BRCA2, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, RAD51C), who received 1–2 chemotherapy regimens (≥1 taxane-based) and progressed on ≥1 NHT (enzalutamide/abiraterone acetate). Pts receive oral TALA 1 mg/d (moderate renal impairment, 0.75 mg/d) until radiographic progression, unacceptable toxicity, or consent withdrawal. Primary endpoint is objective response rate (ORR; blinded independent review). Secondary endpoints are time to OR, duration of response, prostate-specific antigen (PSA) decrease ≥50%, circulating tumor cell (CTC) count conversion (to CTC = 0 and <5 per 7.5 mL of blood), time to PSA progression, radiographic progression-free survival (rPFS), overall survival, safety, pt-reported outcomes, and pharmacokinetics. A planned IA of safety and efficacy was performed after 20 pts with BRCA1/2 mutations were on treatment for ≥8 wks. Results: 81 pts received TALA as of June 5, 2019; 43 pts enrolled by Feb 12, 2019 were evaluable for the primary endpoint (20 BRCA1/2, 2 PALB2, 14 ATM, 7 other). All had received docetaxel and 49% prior cabazitaxel. Overall ORR (95% CI) was 25.6% (13.5–41.2), ORRBRCA1/2 50.0% (27.2–72.8), ORRATM 7.1% (0.2–33.9). Overall median (95% CI) rPFS was 5.6 months (mo) (3.5–8.2), rPFSBRCA1/2 8.2 mo (5.6–NE), rPFSATM 3.5 mo (1.7–8.1). Most common treatment-emergent adverse events (≥20%) were anemia, nausea, asthenia, decreased appetite, constipation, and platelet count decreased. Conclusions: TALA monotherapy demonstrates encouraging antitumor activity in docetaxel-pretreated mCRPC pts, especially those with BRCA1/2mut, and was generally well tolerated. This study was sponsored by Pfizer Inc. Clinical trial information: NCT03148795.
Safety of BXCL701, a small molecule inhibitor of dipeptidyl peptidases (DPP), with pembrolizumab, (pembro, anti-PD-1) monoclonal antibody, in men with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Aggarwal Rahul Raj , Costin Dan , O'Neill Vincent J. , Burg Cedric R , Healey Diane I. , De Bono Johann S. , Zhang Jingsong , Small Eric Jay
Published: February 2020

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Background: BXCL701 (talabostat previously PT100) is an oral small molecule inhibitor of dipeptidyl peptidases (DPP) specifically DPP4, DPP8 and DPP9, which trigger macrophage cell death via pyroptosis resulting in proinflammatory stimulation of the innate immunity pathway. BXCL701 also inhibits fibroblast activation protein (FAP) releasing the FAP-mediated block of T-cell migration into the tumor. Expression of PD-L1 correlates with amplification of DPP8 and DPP9. In syngeneic animal models, significant tumor responses were observed when BXCL701 was used with checkpoint inhibition. Methods: A phase 1b, multicenter study was undertaken. Eligible patients (pts) had progressing mCRPC (PCWG3), at least 1 line of systemic therapy and ≤ 2 lines of cytotoxic chemotherapy for mCRPC, no prior anti-PD-1/PD-L1 or other T-cell directed anti-cancer therapy, and an ECOG PS of ≤ 2. Pts received fixed dose pembro (200mg IV q21 days) with escalating doses of BXCL701 (0.4mg and 0.6mg PO QD days 1-14 of 21-day cycles) using a 3 X 3 design. The key endpoints were safety and identification of the recommended phase 2 dose (RP2D) for the combination. Composite response (RECIST, PSA, CTC) was also assessed. Results: 3 pts were treated at the initial dose level for at least 4 cycles. All pts remain on treatment. No DLT or SAEs were reported. Grade 3 treatment related adverse events (TRAE) were limited to thrombocytopenia with transfusion in 1 pt. The only TRAE reported in more than one pt was hypocalcemia (2 pts). Safety assessment of BXCL701+pembro is ongoing at the final dose escalation cohort. As DPP9 is amplified in approximately 17% of treatment associated small cell/neuroendocrine prostate cancer (tSCNC) compared to 5% or less in the broader prostate cancer population, the Phase 2 portion of this study will be limited to patients with evidence of t-SCNC or de novo SCNC, an aggressive phenotype with poor outcomes. Conclusions: BXCL701 0.4mg QD on days 1 to 14 of 21-day cycle plus pembrolizumab 200 mg IV on day 1 every 21 days is safe in pts with mCRPC. The final dose escalation supporting RP2D will be presented. Clinical trial information: NCT03910660.
Factors associated with positive germline testing results in men with prostate cancer following NCCN guideline expansion.
Authors: Hunt Trevor Charles , Greenberg Samantha , Ambrose Jacob P. , O'Neil Brock B. , Tward Jonathan David
Published: February 2020

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Background: Pathogenic variants (PV) in genes associated with hereditary cancer risk account for over 10% of cases in men with metastatic prostate cancer (PCa). NCCN guidelines encouraging germline testing (GT) in metastatic PCa were recently expanded to include all men with high risk, very high risk, or regional PCa. Previously, we showed that the rate of PV findings did not significantly decrease after expansion of these criteria. In this study, we sought to identify factors associated with a PV finding. Methods: Men with PCa underwent multi-gene GT for PVs from April 2016 – December 2018 according to NCCN guidelines pre- (2016-17) and post-expansion (2018). The association of patient-level factors of interest with a positive GT result, where at least one PV was identified, was modeled with univariate logistic regression while overall model significance was validated with ANOVA. Results: Of 410 men undergoing GT, 44 (10.7%) positive and 366 (89.3%) negative tests resulted. Mean age at diagnosis was 62.2 years. Positive testing remained stable from 9.4% to 11.2% following guideline expansion (p=0.62). None of the patient-level factors of interest were significantly associated with increased odds of a positive GT result in any model generated. These factors included age at diagnosis, race, pretreatment PSA, Gleason grade group, NCCN risk group, and family history of cancer (breast and ovarian, prostate, any cancer). Model p-values ranged from 0.84 for Gleason grade group to 0.12 for family history of any cancer. Conclusions: Future work will need to further elucidate the role of patient-level factors in identifying men with PCa at increased risk for harboring a germline PV. Nonetheless, the lack of identification of other factors associated with positive GT results and a stable PV detection rate of roughly 10% support the recent expansion of NCCN testing guidelines. Given these findings, consideration of even broader NCCN criteria for GT may be justified.
Evaluation of Proclarix, a prostate cancer risk score, used together with magnetic resonance imaging for the diagnosis of clinically significant prostate cancer.
Authors: Pye Hayley , Ahmed Hashim , Heavey Susan , Stopka-Farooqui Urszula , Johnston Edward , Schiess Ralph , Gillessen Silke , Punwani Shonit , Emberton Mark , Whitaker Hayley
Published: February 2020

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Background: The use of multi-parametric magnetic resonance imaging (mpMRI) has been a significant advance in the diagnosis of prostate cancer (PCa) recommended in a number of guidelines. There are considerable resource implications in scanning all men at risk of PCa. Furthermore, a significant number of mpMRIs are reported as indeterminate, leading to unnecessary biopsies. Proclarix is a CE-marked test based on two novel biomarkers, thrombospondin 1 (THBS1) and cathepsin D (CTSD), combined with PSA and age. A software algorithm returns a risk score that can be used as an aid in the identification of clinically significant PCa (any Grade Group 2 or greater). We aimed to assess the potential of Proclarix to identify those men who could safely avoid an upfront mpMRI or those men who could avoid biopsy when the mpMRI was indeterminate. Methods: Proclarix was correlated retrospectively with diagnostic data from 282 men recruited in the INNOVATE study (NCT02689271). INNOVATE involved men undergoing mpMRI followed by targeted and systematic biopsies in those with a suspicious mpMRI. Results: Median age and PSA were 66 (IQR 59-70) and 5.4 (3.8-7.8) ng/mL. 182 (65%) men underwent biopsy and 78 (43%) had GG≥2 PCa. Application of Proclarix in all 282 men undergoing mpMRI resulted in a sensitivity for clinically significant PCa (GG≥2) of 91%, a negative predictive value (NPV) of 92% and 38% specificity. When normalized to the same sensitivity of 91%, %fPSA resulted in both lower NPV (89%) and specificity (28%) when compared to Proclarix. 144 (51%) men had an indeterminate mpMRI of whom 84 (58%) had a biopsy and 13 (15%) had GG≥2 PCa. In these men, Proclarix had an NPV of 100%, at 100% sensitivity and a specificity of 34%. When results were compared using equal sensitivity, PSA density (cut-off 0.05 ng/mL), which is frequently used to inform the need for biopsy, had 10% specificity. Conclusions: The use of Proclarix could potentially allow 38% of men to avoid undergoing an mpMRI. In men with an indeterminate mpMRI, Proclarix could allow one-third to safely avoid biopsies without missing any clinically significant cancer.