bluuebunny/crossref_metadata_2025 huggingface dataset:
Spontaneous subdural haematoma in a neonate requiring urgent surgical evacuation
Authors: Copley Phillip Correia , Dean Bethan , Davidson Angela L. , Jackson Michael , Sokol Drahoslav
Published: September 2020

We describe the unusual case of a clinically significant subdural haematoma without any underlying cause in a term baby delivered by an elective caesarean section, which required surgical evacuation. We review the literature and describe the presentation, investigation and management options in infants with this infrequent condition.
Adding the Coping Power Programme to parent management training: the cost-effectiveness of stacking interventions for children with disruptive behaviour disorders
Authors: Nystrand Camilla , Helander Maria , Enebrink Pia , Feldman Inna , Sampaio Filipa
Published: September 2020

Parent management training (PMT) programmes and child cognitive behavioural therapy are recommended approaches for treatment of oppositional defiant disorder in children, and combining these may be effective. However, little is known regarding the economic efficiency of this additive effect. A within-trial cost-effectiveness analysis was carried out in Sweden including 120 children aged 8–12 who screened positive for disruptive behaviour disorders, within a psychiatric care setting, and their parents. They were randomly assigned to either the Swedish group-based PMT Comet, or to an enhanced version, where an additional child component was provided, the Coping Power Programme (CPP). Child behaviour problems as well as healthcare and educational resource use were measured at baseline, post-test and at two-year follow-up. A net benefit regression framework was used to estimate differences in costs and health outcomes between the two intervention arms during the two-year period. Comet with CPP cost on average 820 EURO more per family than Comet only. At the 2-year follow-up, there were 37% recovered cases of ODD in Comet with CPP, in comparison to 26% in the Comet only arm. At a willingness-to-pay of approximately 62,300 EURO per recovered case of ODD, Comet with CPP yielded positive net benefits, in comparison to Comet only. Offering children the CPP simultaneously as their parents receive PMT, in comparison to only providing PMT, yields clinically relevant gains. Despite the relatively small cost for CPP, investment in combining PMT and CPP should be guided by resource prioritisation. Trial registration number: ISRCTN10834473, date of registration: 23/12/2015
Recycling behavior of private households: an empirical investigation of individual preferences in a club good experiment
Authors: Menges Roland , Cloos Janis , Greiff Matthias , Wehrle Jacob , Goldmann Daniel , Rabe Lisa
Published: September 2020

While recycling helps to limit the use of primary resources, it also requires considerable technological investments in regional circular flow systems. The effectiveness of recycling systems, however, also depends on household behavior. Therefore, current research increasingly focuses on behavioral and psychological theories of altruism, moral behavior, and social preferences. From an economic perspective, recycling systems can be understood as public goods with contributions resulting in positive externalities. In this context, the literature shows that recycling behavior highly depends on the perception of how others behave. In neutrally framed public good experiments, contributions tend to increase when alternative public goods are offered and group identity is generated. We aim to contribute to this discussion by observing household behavior concerning recycling opportunities in controlled settings. For this purpose, we study a laboratory experiment in which individuals contribute to recycling systems: At first, only one public recycling system (public good) is offered. After dividing societies into two clubs, “high” and “low” according to their environmental attitudes, excludable club systems (club goods) are added as alternative recycling options for each club. The results of our pilot experiment show that adding a more exclusive recycling club option increases individual contributions to recycling compared with a pure public good framework. However, this increase in cooperation is only significant for those clubs where members with higher environmental attitudes are pooled.

Graphic abstract
Challenges in approximating the Black and Scholes call formula with hyperbolic tangents
Authors: Mininni Michele , Orlando Giuseppe , Taglialatela Giovanni
Published: September 2020

In this paper, we introduce the concept of standardized call function and we obtain a new approximating formula for the Black and Scholes call function through the hyperbolic tangent. Differently from other solutions proposed in the literature, this formula is invertible; hence, it is useful for pricing and risk management as well as for extracting the implied volatility from quoted options. The latter is of particular importance since it indicates the risk of the underlying and it is the main component of the option’s price. That is what trading desks focus on. Further we estimate numerically the approximating error of the suggested solution and, by comparing our results in computing the implied volatility with the most common methods available in the literature, we discuss the challenges of this approach.
The efficacy and safety of pertuzumab plus trastuzumab and docetaxel as a first-line therapy in Japanese patients with inoperable or recurrent HER2-positive breast cancer: the COMACHI study
Authors: Takahashi Masato , Ohtani Shoichiro , Nagai Shigenori E. , Takashima Seiki , Yamaguchi Miki , Tsuneizumi Michiko , Komoike Yoshifumi , Osako Tomofumi , Ito Yoshinori , Ikeda Masahiko , Ishida Kazushige , Nakayama Takahiro , Takashima Tsutomu , Asakawa Takashi , Matsumoto Sho , Shimizu Daisuke , Masuda Norikazu
Published: September 2020

Purpose

In the CLEOPATRA study of patients with human epidermal growth factor receptor 2 (HER2)-positive recurrent or metastatic breast cancer, the Japanese patient subgroup did not demonstrate the improved progression-free survival (PFS) of pertuzumab plus trastuzumab and docetaxel vs. placebo that was seen in the overall population. Therefore, COMACHI was conducted to confirm the efficacy and safety of this treatment regimen in this patient subgroup.

Methods

This was a phase IV study of pertuzumab plus trastuzumab and docetaxel in Japanese patients with histologically/cytologically confirmed inoperable or recurrent HER2-positive breast cancer. All patients received pertuzumab, trastuzumab, and docetaxel intravenously every 3 weeks until disease progression/unacceptable toxicity. The primary endpoint was investigator-assessed PFS. Secondary endpoints were overall survival (OS), investigator-assessed objective response rate, and duration of response (DoR). Safety was also assessed.

Results

At final analysis, median investigator-assessed PFS was 22.8 months (95% CI 16.9–37.5). From first dose, OS rate at 1 year was 97.7%; and at 2 and 3 years were 88.5% and 79.1%, respectively. Of the 118 patients with measurable disease at baseline, response rate was 83.9% (95% CI 77.3–90.5) and median investigator-assessed DoR was 26.3 months (95% CI 17.1–not evaluable). Treatment was well tolerated, with no new safety signals detected.

Conclusions

Our results suggest similar efficacy and safety for pertuzumab plus trastuzumab and docetaxel in Japanese patients compared with the overall population of CLEOPATRA, providing further support for this combination therapy as standard of care for Japanese patients with inoperable or recurrent HER2-positive breast cancer.
Is repeated pulmonary metastasectomy justified?
Authors: Forster Céline , Ojanguren Amaya , Perentes Jean Yannis , Zellweger Matthieu , Federici Sara , Krueger Thorsten , Abdelnour-Berchtold Etienne , Gonzalez Michel
Published: September 2020

Recurrence after pulmonary metastasectomy (PM) is frequent, but it is unclear to whom repeated pulmonary metastasectomy (RPM) offers highest benefits. Retrospective analysis of oncological and post-operative outcomes of consecutive patients who underwent PM from 2003 to 2018. Overall survival (OS) and disease-free interval (DFI) were calculated. Cox regression was used to identify variables influencing OS and DFI. In total, 264 patients (female/male: 114/150; median age: 62 years) underwent PM for colorectal cancer (32%), sarcoma (19%), melanoma (16%) and other primary tumors (33%). Pulmonary metastasectomy was approached by video-assisted thoracic surgery (VATS) in 73% and pulmonary resection was realized by non-anatomical resection in 76% of cases. The overall median follow-up time was 33 months (IQR 16–56 months) and overall 5-year survival rate was 62%. Local or distant recurrences were observed in 172 patients (65%) and RPM could be performed in 66 patients (25%) for a total of 116 procedures. RPM was realized by VATS in 49% and pulmonary resection by wedge in 77% of cases. In RPM patients, the 5-year survival rate after first PM was 79%. Post-operative cardio-pulmonary complication rate (13% vs. 12%; p = 0.8) and median length of stay (4 vs. 5 days; p = 0.2) were not statistically different between first PM and RPM. Colorectal cancer (HR 0.56), metachronous metastasis (HR 0.48) and RPM (HR 0.5) were associated with better survival. In conclusion, our results suggest that RPM offers favorable survival rates without increasing post-operative morbidity.
Phase II trial of SM-88, a cancer metabolism based therapy, in non-metastatic biochemical recurrent prostate cancer
Authors: Gartrell Benjamin A. , Roach Mack , Retter Avi , Sokol Gerald H. , Del Priore Giuseppe , Scher Howard I.
Published: September 2020

BackgroundAndrogen deprivation therapy (ADT) is a standard treatment for high-risk biochemically-recurrent, non-metastatic prostate cancer (BRPC) but is not curative and associated with toxicity. Racemetyrosine (SM-88) is an amino-acid analogue used with methoxsalen, phenytoin, and sirolimus (MPS) to enhance SM-88 activity.MethodA phase 1b/2, open-label trial in BRPC and rising PSA. Patients were given daily SM-88 (230 mg BID), methoxsalen (10 mg), phenytoin (50 mg), and sirolimus (0.5 mg)). Outcome measures included changes in PSA, circulating tumor cells (CTCs) and imaging.Results34 subjects were screened, 23 treated and 21 remained on study for ≥12 weeks. The median PSA was 6.4 ng/ml (range 1.7–80.1); doubling-time 6.2 months (range 1.4–36.6) and baseline testosterone 319.1 ng/ml (range 2.5–913.7). Median duration of therapy was 6.5 months (2.6–14.0). CTCs (median 48.5 cells/4 ml (range 15–268) at baseline) decreased a median of 65.3% in 18 of 19 patients. For patients who achieved an absolute CTC nadir count of <10 cells/4 ml (n = 10), disease control was 100% i.e. no metastases or PSA progression, while on trial (p = 0.005). PSA fell by≥50% in 4.3% (1 subject). No patients developed metastatic disease while on treatment (metastases free survival =100%). There were no treatment-related adverse events (AEs) and quality of life was unchanged from baseline on the EORTC QLQ-C30 and QLQ-PR25. Testosterone levels rose slightly on SM-88 and were unrelated to efficacy or toxicity.ConclusionsUse of SM-88 was associated with disease control while maintaining QOL. SM-88 may delay the need for ADT and the associated hormonal side effects. Larger trials are planned.

Trial registration number, date of registration - NCT02796898, June 13, 2016
Automated demarcation of requirements in textual specifications: a machine learning-based approach
Authors: Abualhaija Sallam , Arora Chetan , Sabetzadeh Mehrdad , Briand Lionel C. , Traynor Michael
Published: September 2020

A simple but important task during the analysis of a textual requirements specification is to determine which statements in the specification represent requirements. In principle, by following suitable writing and markup conventions, one can provide an immediate and unequivocal demarcation of requirements at the time a specification is being developed. However, neither the presence nor a fully accurate enforcement of such conventions is guaranteed. The result is that, in many practical situations, analysts end up resorting to after-the-fact reviews for sifting requirements from other material in a requirements specification. This is both tedious and time-consuming. We propose an automated approach for demarcating requirements in free-form requirements specifications. The approach, which is based on machine learning, can be applied to a wide variety of specifications in different domains and with different writing styles. We train and evaluate our approach over an independently labeled dataset comprised of 33 industrial requirements specifications. Over this dataset, our approach yields an average precision of 81.2% and an average recall of 95.7%. Compared to simple baselines that demarcate requirements based on the presence of modal verbs and identifiers, our approach leads to an average gain of 16.4% in precision and 25.5% in recall. We collect and analyze expert feedback on the demarcations produced by our approach for industrial requirements specifications. The results indicate that experts find our approach useful and efficient in practice. We developed a prototype tool, named DemaRQ, in support of our approach. To facilitate replication, we make available to the research community this prototype tool alongside the non-proprietary portion of our training data.
An Empirical Investigation of Relevant Changes and Automation Needs in Modern Code Review
Authors: Panichella Sebastiano , Zaugg Nik
Published: September 2020

Recent research has shown that available tools for Modern Code Review (MCR) are still far from meeting the current expectations of developers. The objective of this paper is to investigate the approaches and tools that, from a developer’s point of view, are still needed to facilitate MCR activities. To that end, we first empirically elicited a taxonomy of recurrent review change types that characterize MCR. The taxonomy was designed by performing three steps: (i) we generated an initial version of the taxonomy by qualitatively and quantitatively analyzing 211 review changes/commits and 648 review comments of ten open-source projects; then (ii) we integrated into this initial taxonomy, topics, and MCR change types of an existing taxonomy available from the literature; finally, (iii) we surveyed 52 developers to integrate eventually missing change types in the taxonomy. Results of our study highlight that the availability of new emerging development technologies (e.g., Cloud-based technologies) and practices (e.g., Continuous delivery) has pushed developers to perform additional activities during MCR and that additional types of feedback are expected by reviewers. Our participants provided recommendations, specified techniques to employ, and highlighted the data to analyze for building recommender systems able to automate the code review activities composing our taxonomy. We surveyed 14 additional participants (12 developers and 2 researchers), not involved in the previous survey, to qualitatively assess the relevance and completeness of the identified MCR change types as well as assess how critical and feasible to implement are some of the identified techniques to support MCR activities. Thus, with a study involving 21 additional developers, we qualitatively assess the feasibility and usefulness of leveraging natural language feedback (automation considered critical/feasible to implement) in supporting developers during MCR activities. In summary, this study sheds some more light on the approaches and tools that are still needed to facilitate MCR activities, confirming the feasibility and usefulness of using summarization techniques during MCR activities. We believe that the results of our work represent an essential step for meeting the expectations of developers and supporting the vision of full or partial automation in MCR.
The Significance of Value Additivity
Authors: Brown Campbell
Published: September 2020

Whether value is “additive,” that is, whether the value of a whole must equal the sum of the values of its parts, is widely thought to have significant implications in ethics. For example, additivity rules out “organic unities,” and is presupposed by “contrast arguments.” This paper reconsiders the significance of value additivity. The main thesis defended is that it is significant only for a certain class of “mereologies”, roughly, those in which both wholes and parts are “complete”, in the sense that they can exist independently. For example, value additivity is significant in the case of a mereology of material objects, but not in the case of a mereology of propositions.
Mapping QTLs for tolerance to salt stress at the early seedling stage in rice (Oryza sativa L.) using a newly identified donor ‘Madina Koyo’
Authors: Amoah Nana Kofi Abaka , Akromah Richard , Kena Alex Wireko , Manneh Baboucarr , Dieng Ibnou , Bimpong Isaac Kofi
Published: September 2020

Salt stress is a menace to rice production and a threat to food security worldwide. We evaluated 308 F4 families from Sahel 317/Madina Koyo for tolerance to salt stress at the early seedling stage. To better understand genomic regions controlling tolerance in the population, we genotyped the progenies and the two parents using single nucleotide polymorphism (SNP) markers and regressed the genotypic data on their phenotype to detect QTLs. An average reduction of 63.4% was observed for all fitness-related traits among the F4 families. A total of 46 progenies recorded an average salt injury score (SIS) between 1–3 and were rated as tolerant to salt stress at the early seedling stage. A high-density genetic map was constructed for the 12 rice chromosomes using 3698 SNP markers. Multiple interval mapping identified 13 QTLs for SIS, shoot length, shoot dry weight and root length on chromosomes 2, 3, 4, 6, 7, 10 and 12, with trait increasing alleles coming from both parents. Two (qSDW2 and qRL2.2) and three (qSL2, qRL2.1 and qSIS2) QTLs at different regions on chromosome 2 and another two on chromosome 7 (qSDW7 and qSL7) were tightly linked. These QTLs could facilitate breeding for salt tolerance at the early seedling stage as direct selection for one, would mean indirectly selecting for the other. Fine mapping of these novel QTLs in a different genetic background is necessary to confirm their stability and usefulness in breeding for tolerance to salinity in rice.
Backward Stochastic Differential Equations Driven by G-Brownian Motion with Double Reflections
Authors: Li Hanwu , Song Yongsheng
Published: September 2020

In this paper, we study the reflected backward stochastic differential equations driven by G-Brownian motion with two reflecting obstacles, which means that the solution lies between two prescribed processes. A new kind of approximate Skorohod condition is proposed to derive the uniqueness and existence of the solutions. The uniqueness can be proved by a priori estimates and the existence is obtained via a penalization method.
Designable elements of integrative learning environments at the boundary of school and work: a multiple case study
Authors: Bouw Erica , Zitter Ilya , de Bruijn Elly
Published: September 2020

Learning environment designs at the boundary of school and work can be characterised as integrative because they integrate features from the contexts of school and work. Many different manifestations of such integrative learning environments are found in current vocational education, both in senior secondary education and higher professional education. However, limited research has focused on how to design these learning environments and not much is known about their designable elements (i.e. the epistemic, spatial, instrumental, temporal and social elements that constitute the learning environments). The purpose of this study was to examine manifestations of two categories of integrative learning environment designs: designs based on incorporation; and designs based on hybridisation. Cross-case analysis of six cases in senior secondary vocational education and higher professional education in the Netherlands led to insights into the designable elements of both categories of designs. We report findings about the epistemic, spatial, instrumental, temporal and social elements of the studied cases. Specific characteristics of designs based on incorporation and designs based on hybridisation were identified and links between the designable elements became apparent, thus contributing to a deeper understanding of the design of learning environments that aim to connect the contexts of school and work.
Polynomials under Ornstein–Uhlenbeck noise and an application to inference in stochastic Hodgkin–Huxley systems
Authors: Höpfner Reinhard
Published: September 2020

We discuss estimation problems where a polynomial $$s\rightarrow \sum _{i=0}^\ell \vartheta _i s^i$$

s
→

∑

i
=
0

ℓ

ϑ
i

s
i

with strictly positive leading coefficient is observed under Ornstein–Uhlenbeck noise over a long time interval. We prove local asymptotic normality (LAN) and specify asymptotically efficient estimators. We apply this to the following problem: feeding noise $$dY_t$$

d

Y
t

into the classical (deterministic) Hodgkin–Huxley model in neuroscience, with $$Y_t=\vartheta t + X_t$$

Y
t

=
ϑ
t
+

X
t

and X some Ornstein–Uhlenbeck process with backdriving force $$\tau $$
τ
, we have asymptotically efficient estimators for the pair $$(\vartheta ,\tau )$$

(
ϑ
,
τ
)

; based on observation of the membrane potential up to time n, the estimate for $$\vartheta $$
ϑ
converges at rate $$\sqrt{n^3\,}$$

n
3

.
A Review of HIV Pre-exposure Prophylaxis Streamlining Strategies
Authors: Siegler Aaron J. , Steehler Kevin , Sales Jessica M. , Krakower Douglas S.
Published: September 2020

Purpose of Review

Standard care for HIV pre-exposure prophylaxis (PrEP) in the USA creates substantial burdens for patients, clinicians, and the healthcare system; to optimize uptake, there is a need for innovative strategies to streamline its provision.

Recent Findings

Our review, structured by the expanded chronic care model, identified eleven promising strategies to streamline PrEP care. Approaches ranged widely in mechanism of action. Using text messages to support care was the only strategy with clinical trial evidence supporting its use. Other modalities such as patient navigation, telemedicine PrEP models, alternate dosing availability, same-day prescription, and provider training have promising pilot or associational data and seem likely to lower barriers to entering into or remaining in care. Many of the strategies have established success in related domains such as HIV care, meriting consideration in evaluating their use for PrEP.

Making PrEP care less burdensome will be an important part of bringing it to scale. Text message interventions have proven efficacy and merit broad adoption. Encouraging preliminary evidence for other strategies indicates the importance of building a stronger evidence base to clarify the effect of each strategy. Ongoing development of an evidence base should not delay the use of these promising strategies; instead, it calls for careful consideration for how each program may best match its environment to facilitate PrEP prescribing and use.
Forests in common: Learning from diversity of community forest arrangements in Europe
Authors: Lawrence Anna , Gatto Paola , Bogataj Nevenka , Lidestav Gun
Published: September 2020

Europe has a wealth of community forest arrangements. This paper aims to transcend the diversity of locally specific terms and forms, to highlight the value of considering them inclusively. Building on methods to make sense of diversity, we use reflexive grounded inquiry in fifteen cases in Italy, Scotland, Slovenia and Sweden. Within four dimensions (forest, community, relationships between them, and relationships with wider society), we identify 43 subdimensions to describe them collectively. Our approach shows how European arrangements contribute to wider discourses of collective natural resource management. Both tradition and innovation in Europe inform options for environmental governance. Arrangements challenge the distinction between ‘communities of place’ and ‘communities of interest’, with implications for social and environmental justice. They exemplify multilevel environmental governance through both vertical and horizontal connections. Emerging from long histories of political and environmental pressures, they have a role in enhancing society’s connection with nature and adaptive capacity.
The missing pieces for better future predictions in subarctic ecosystems: A Torneträsk case study
Authors: Pascual Didac , Åkerman Jonas , Becher Marina , Callaghan Terry V. , Christensen Torben R. , Dorrepaal Ellen , Emanuelsson Urban , Giesler Reiner , Hammarlund Dan , Hanna Edward , Hofgaard Annika , Jin Hongxiao , Johansson Cecilia , Jonasson Christer , Klaminder Jonatan , Karlsson Jan , Lundin Erik , Michelsen Anders , Olefeldt David , Persson Andreas , Phoenix Gareth K. , Rączkowska Zofia , Rinnan Riikka , Ström Lena , Tang Jing , Varner Ruth K. , Wookey Philip , Johansson Margareta
Published: September 2020

Arctic and subarctic ecosystems are experiencing substantial changes in hydrology, vegetation, permafrost conditions, and carbon cycling, in response to climatic change and other anthropogenic drivers, and these changes are likely to continue over this century. The total magnitude of these changes results from multiple interactions among these drivers. Field measurements can address the overall responses to different changing drivers, but are less capable of quantifying the interactions among them. Currently, a comprehensive assessment of the drivers of ecosystem changes, and the magnitude of their direct and indirect impacts on subarctic ecosystems, is missing. The Torneträsk area, in the Swedish subarctic, has an unrivalled history of environmental observation over 100 years, and is one of the most studied sites in the Arctic. In this study, we summarize and rank the drivers of ecosystem change in the Torneträsk area, and propose research priorities identified, by expert assessment, to improve predictions of ecosystem changes. The research priorities identified include understanding impacts on ecosystems brought on by altered frequency and intensity of winter warming events, evapotranspiration rates, rainfall, duration of snow cover and lake-ice, changed soil moisture, and droughts. This case study can help us understand the ongoing ecosystem changes occurring in the Torneträsk area, and contribute to improve predictions of future ecosystem changes at a larger scale. This understanding will provide the basis for the future mitigation and adaptation plans needed in a changing climate.
Nordic Bioeconomy Pathways: Future narratives for assessment of water-related ecosystem services in agricultural and forest management
Authors: Rakovic Jelena , Futter Martyn N. , Kyllmar Katarina , Rankinen Katri , Stutter Marc I. , Vermaat Jan , Collentine Dennis
Published: September 2020

Further development of the bioeconomy, the substitution of bioresources for fossil resources, will lead to an increased pressure on land and water resources in both agriculture and forestry. It is important to study whether resultant changes in land management may in turn lead to impairment of water services. This paper describes the Nordic Bioeconomy Pathways (NBPs), a set of regional sectoral storylines nested within the global Shared Socioeconomic Pathways (SSP) framework developed to provide the BIOWATER research program with land management scenarios for projecting future developments to explore possible conflicts between land management changes and the Water Framework Directive (WFD). The NBPs are a set of narrative storylines capturing a range of plausible future trajectories for the Nordic bioeconomy until 2050 and that are fit for use within hydrological catchment modelling, ecosystem service studies and stakeholder dialogue about possible changes in agricultural and forestry management practices.
FOXO3 is targeted by miR-223-3p and promotes osteogenic differentiation of bone marrow mesenchymal stem cells by enhancing autophagy
Authors: Long Cheng , Cen Shiqiang , Zhong Zhou , Zhou Chang , Zhong Gang
Published: September 2020

Mesenchymal stem cells (MSCs) are a promising regenerative medicine. The roles of miRNAs in osteogenic differentiation of bone marrow MSCs (BM-MSCs) remained less reported. Forkhead Box O3 (FOXO3) and alkaline phosphatase (ALP) levels in the BM-MSCs were measured on 3, 7, and 14 days after osteogenic differentiation. After transfection of FOXO3 overexpression plasmids or siFOXO3 into BM-MSCs, factors related to osteogenic differentiation or cell autophagy were determined. Besides, 3-methyladenine or rapamycin, as well as miR-223-3p mimic or inhibitor were applied to further determine the effect of FOXO3 in BM-MSCs. FOXO3 and ALP levels were increased in a time-dependent manner with osteogenic differentiation, supported by Alizarin Red Staining. Furthermore, up-regulated FOXO3 increased levels of ALP and factors related to osteogenic differentiation by increasing levels of autophagy-related factors. FOXO3, targeted by miR-223-3p, reversed the effects of miR-223-3p on factors related to BM-MSC autophagy and osteogenic differentiation. Down-regulated miR-223-3p expression promoted osteogenic differentiation of BM-MSCs by enhancing autophagy via targeting FOXO3, suggesting the potential of miR-223-3p as a therapeutic target for enhancing bone functions.
Alexithymia and metabolic syndrome: the mediating role of binge eating
Authors: Conti Chiara , Di Francesco Giulia , Severo Melania , Lanzara Roberta , Richards Katie , Guagnano Maria Teresa , Porcelli Piero
Published: September 2020

Purpose

Alexithymia, a personality trait characterized by difficulties in emotional processing, has been associated with unhealthy behaviors and chronic medical conditions. This study aimed to further develop our understanding of this complex relationship by investigating whether alexithymia increases the risk of metabolic syndrome (MetS) in participants with obesity or overweight through the mediating role of binge eating (BE).

Methods

A consecutive sample of 238 treatment-seeking patients with obesity or overweight were recruited. Alexithymia (TAS-20), binge eating symptoms (BES), body mass index (BMI), and depression and anxiety symptoms (HADS) were concurrently assessed.

Results

Almost half of the participants met the criteria for MetS (44.12%). Compared to patients without MetS, those with MetS were older, had a longer duration of overweight, and had a higher BMI (p < 0.01). Individual with MetS also had higher HADS, BES, and TAS-20 scores, particularly difficulty identifying and describing feelings. The structural equation modeling (SEM) analysis revealed that BES levels exerted a significant direct effect on MetS (p < 0.01), and that TAS-20 levels exerted a significant direct effect on BES (p < 0.01), anxiety (p < 0.001) and depression (p < 0.001). Moreover, psychological distress (anxiety, p = 0.01, and depression, p = .05) indirectly affected MetS through the mediating effect of BES, and TAS-20 (p = 0.01) indirectly affected MetS through the mediating effect of HADS and BES. Finally, age had a significant direct effect on MetS (p < 0.001).

Conclusion

Our findings indicate that alexithymia is a concurrent causative factor to the development of MetS through the mediating role of BE and psychological distress.

Level of evidence

Level III, case–control analytic study.
Smart healthcare solutions using the internet of medical things for hand gesture recognition system
Authors: Mahmoud Nourelhoda M. , Fouad Hassan , Soliman Ahmed M.
Published: September 2020

Patient gesture recognition is a promising method to gain knowledge and assist patients. Healthcare monitoring systems integrated with the Internet of Things (IoT) paradigm to perform the remote solutions for the acquiring inputs. In recent years, wearable sensors, and information and communication technologies are assisting for remote monitoring and recommendations in smart healthcare. In this paper, the dependable gesture recognition (DGR) using a series learning method for identifying the action of patient monitoring through remote access is presented. The gesture recognition systems connect to the end-user (remote) and the patient for instantaneous gesture identification. The gesture is recognized by the analysis of the intermediate and structuring features using series learning. The proposed gesture recognition system is capable of monitoring patient activities and differentiating the gestures from the regular actions to improve the convergence. Gesture recognition through remote monitoring is indistinguishable due to the preliminary errors. Further, it is convertible using series learning. Therefore, the misdetections and classifications are promptly identified using the DGR and verified by comparative analysis and experimental study. From the analysis, the proposed DGR approach attains 94.92% high precision for the varying gestures and 89.85% high accuracy for varying mess factor. The proposed DGR reduces recognition time to 4.97 s and 4.93 s for the varying gestures and mess factor, respectively.
Family environment and school engagement:An investigation of cross‐lagged effects
Authors: Harris Charlene , Vazsonyi Alexander T. , Özdemir Yalçın , Sağkal Ali Serdar
Published: September 2020

Introduction

Although an extensive body of work has shown that family functioning is linked to adolescent outcomes, less is known about how the family affects school outcomes and vice versa. The present longitudinal study tested reciprocal relationships between the family environment and school engagement during the middle school years.

Methods

A cross‐lagged latent model tested these effects in 378 Turkish youth (53.7% males;M= 11.73,SD= 0.53) evaluated annually (Waves 1, 2, and 3) in grades 6 through 8.

Results

Findings showed the family environment positively predicted developmental changes in school engagement at each time point (β range = 0.18 to 0.24); school engagement also positively predicted developmental changes in the family environment (β range = 0.12 to 0.28). Follow‐up multigroup tests by age, sex, and family structure showed that the reciprocal links between the family environment and school engagement were invariant.

Conclusions

Study findings supported reciprocal longitudinal links between developmental changes of the family environment and school engagement. They extend previous research by highlighting the continued importance of the home environment on developmental changes in academic performance in adolescents, and thus, inform parents, educators, and policymakers on the relevance of the family in promoting academic engagement and achievement in adolescence.
Emotional separation, parental trust, and psychosocial adjustment in preadolescence and early adolescence
Authors: Sugimura Kazumi , Hihara Shogo , Hatano Kai
Published: September 2020

Introduction

Emotional separation and parental trust are two fundamental components of parent‐adolescent relationships across different cultural contexts. Previous research showed that emotional separation hindered adolescents’ psychosocial adjustment, while parental trust benefited it. However, research on preadolescence is lacking. Preadolescence is a crucial period, as theories and findings suggest that too early autonomy around puberty had negative consequences for psychosocial adjustment. This study focused on preadolescence and early adolescence and tested two hypotheses: that emotional separation would be negatively, and parental trust would be positively, associated with psychosocial adjustment, and that this pattern of associations would be more salient in preadolescence than in early adolescence.

Methods

Participants were 856 preadolescent elementary schoolers (49.6% girls; age range 9–12 years, Mage = 10.79, SD = 0.92) and 518 early adolescent junior high schoolers (47.7% girls, age range 12–15 years; Mage = 13.56, SD = 0.98) in Japan, who completed measures of emotional separation, parental trust, and psychosocial adjustment (industry, school adaptation, and daily life behaviors).

Results

Emotional separation was negatively associated with reviewing learning contents and doing homework. Parental trust was positively associated with industry, school adaptation, waking up at regular times, and observing rules at school. These relationships did not differ between age groups.

Conclusions

This study highlights that emotional separation has a negative relationship, and parental trust has a positive relationship, with psychosocial adjustment throughout preadolescence and adolescence.
PD-1 blockade as a future treatment for colorectal cancer with microsatellite instability
Authors: Russo Diana Maria Leite da Cunha , Barbosa Laura Elisabete Ribeiro
Published: September 2020

Introduction Colorectal cancer is the third most common cancer worldwide, with about 15% of these tumours related with microsatellite instability, which confers distinct characteristics to these tumours, both clinicopathological and in the response to treatments. In fact, the poor response to chemotherapy in these tumours has led to the investigation for new treatments, with immunotherapy being the most successful one to date. The focus of this review is to assess the response of microsatellite unstable colorectal cancer to PD-1 blockade, and the mechanisms behind that response.

Methods A PubMed research was conducted, resulting in the inclusion of 47 articles in this review.

Results Microsatellite instability results in a high neoantigen load, leading to a highly active immune microenvironment of the tumour, mainly due to T-cells. To counteract this, there is an upregulation of PD-1, acting as a “brake” for immune cells, facilitating tumour growth and metastasis. This upregulation makes these tumours great candidates for treatment with PD-1 blockade, as seen in many clinical trials, where the overall responses and progression free survival rates were higher than those observed in microsatellite stable tumours.

Conclusion With the importance of colorectal cancer with microsatellite instability new treatments are necessary. Therefore, PD-1 blockade is a promising treatment for colorectal cancer with microsatellite instability, with improvement in survival rates and a better prognosis for these patients.
Fournier’s gangrene by perianal abscess
Authors: de Souza Natiele Santos , Santos Djoney Rafael dos , Westphalen André Pereira , Netto Fernando Antonio Campelo Spencer
Published: September 2020

Objective To describe and analyze the cases of Fournier’s Gangrene caused by perianal abscess treated in a tertiary hospital in western Paraná, correlating possible factors that influence mortality, with emphasis on late diagnosis and therapy.

Methods A retrospective and descriptive case series was carried out based on the analysis of medical records of patients with Fournier’s Gangrene due to perianal abscess from January 2012 to December 2017.

Results Thirty-one patients with Fournier’s Gangrene due to perianal abscess were treated in the period: 26 men and 5 women. Mean age was 53.51 ± 14.5 years. The most prevalent comorbidity in this group was type 2 diabetes mellitus, showing a strong correlation with mortality. The mean time from disease progression, from the initial symptom to the admission at the service, was 9.6 ± 6.81 days. All patients were submitted to antibiotic therapy and surgical treatment, with a mean of 3.25 ± 2.89 procedures/patient. Seven (22.58%) patients died and all of them showed signs of sepsis on admission; only 2 patients with sepsis did not die.

Conclusion The presence of sepsis on admission and type 2 diabetes mellitus were strongly correlated with mortality.
Procalcitonin as an early marker in the detection of anastomotic intestinal leak in a Universitary Hospital of Bogotá
Authors: Navarrete Elkin Eduardo Benítez , Beltrán-García Tatiana Carolina , Mosquera María Fernanda , Rojas Valeria Martinez , Medina Daniel Alejandro Buitrago , Avendaño Carlos Edgar Figueroa
Published: September 2020

Introduction Anastomotic leakage is a complication of intestinal anastomosis, with an incidence of 2%–7% in centers of experience. To be able to achieve an early detection, serological markers such as Procalcitonin were included.

Methods Descriptive retrospective cohort study of patients taken to colorectal surgery with intestinal anastomosis, the objective is to estimate association between procalcitonin (≥2 ng/dl) as an early inflammatory marker and anastomotic leakage in a Coloproctological Service of a highest level of health care hospital, between September 2017 and January 2019.

Results Cohort of 237 patients, 51% women (18–89 years), with multiple comorbidities in 81% of patients, colon cancer was the most operated pathology (53.1%). Laparoscopic approach was the most applied 60.34%, colorectal anastomosis was the most frequently performed (47.26%). Ileocolic anastomosis presented a higher frequency (43.75%-n:7) of dehiscence. Anastomotic leakage was associated with a serum procalcitonin positive 3 days postoperatively (p-value <0.05). Patients with a positive result had 4.28 times higher risk of presenting an anastomotic leak, compared to this risk in those patients with negative results 3 days postoperatively, this association was statistically significant 95% CI (1.34–14.16); p value <0.05.

Conclusion Anastomotic leakage is a source of morbidity in patients taken to intestinal anastomosis. It's necessary to guarantee an early diagnosis of this complication, prevent abscesses and secondary peritonitis, providing adequate treatment and even reducing the associated mortality. We recommend including the procalcitonin in the assessment protocol on the third day of postoperative follow-up.
Obesity treatment effect in Danish children and adolescents carrying Melanocortin-4 Receptor mutations
Authors: Trier Cæcilie , Hollensted Mette , Schnurr Theresia M. , Lund Morten Asp Vonsild , Nielsen Tenna Ruest Haarmark , Rui Gao , Andersson Ehm Astrid , Svendstrup Mathilde , Bille Dorthe Sadowa , Gjesing Anette P. , Fonvig Cilius Esmann , Frithioff-Bøjsøe Christine , Balslev-Harder Marie , Quan Shi , Gamborg Michael , Pedersen Oluf , Ängquist Lars , Holm Jens-Christian , Hansen Torben
Published: September 2020

Objectives

To determine the prevalence of Melanocortin-4 Receptor (MC4R) mutations in a cohort of children and adolescents with overweight or obesity and to determine whether treatment responses differed between carriers and noncarriers.

Methods

Using target region capture sequencing, an MC4R mutation screen was performed in 1261 Danish children and adolescents enrolled at a tertiary multidisciplinary childhood obesity treatment center. Measurements of anthropometrics, blood pressure, fasting blood biochemistry including lipid and hormone levels, and dual-energy X-ray absorptiometry were performed at baseline and throughout treatment.

Results

Of 1209 children and adolescents that met all criteria to be included in the described analyses, 30 (2.5%) carried damaging or unresolved MC4R mutations. At baseline, mutation carriers exhibited higher concentrations of plasma thyroid-stimulating hormone (p = 0.003), and lower concentrations of plasma thyroxine (p = 0.010) compared to noncarriers. After a median of 1 year of treatment (range 0.5–4.0 years), body mass index (BMI) standard deviation score (SDS) was reduced in noncarriers but not in carriers, and this difference in treatment response was statistically significant (p = 0.005). Furthermore, HDL cholesterol was reduced in carriers, a response significantly different from that of noncarriers (p = 0.017).

Conclusion

Among Danish children and adolescents with overweight or obesity entering a tertiary lifestyle intervention, 2.5% carried damaging or unresolved MC4R mutations. In contrast to noncarriers, carriers of damaging or unresolved MC4R mutations failed to reduce their BMI SDS during obesity treatment, indicating a need for personalized treatment based on the MC4R genotype.
Investigation of glycaemic traits in psychiatric disorders using Mendelian randomisation revealed a causal relationship with anorexia nervosa
Authors: Adams Danielle M. , Reay William R. , Geaghan Michael P. , Cairns Murray J.
Published: September 2020

Data from observational studies have suggested an involvement of abnormal glycaemic regulation in the pathophysiology of psychiatric illness. This may be an attractive target for clinical intervention as glycaemia can be modulated by both lifestyle factors and pharmacological agents. However, observational studies are inherently confounded, and therefore, causal relationships cannot be reliably established. We employed genetic variants rigorously associated with three glycaemic traits (fasting glucose, fasting insulin, and glycated haemoglobin) as instrumental variables in a two-sample Mendelian randomisation analysis to investigate the causal effect of these measures on the risk for eight psychiatric disorders. A significant protective effect of a natural log transformed pmol/L increase in fasting insulin levels was observed for anorexia nervosa after the application of multiple testing correction (OR = 0.48 [95% CI: 0.33-0.71]—inverse-variance weighted estimate). There was no consistently strong evidence for a causal effect of glycaemic factors on the other seven psychiatric disorders considered. The relationship between fasting insulin and anorexia nervosa was supported by a suite of sensitivity analyses, with no statistical evidence of instrument heterogeneity or horizontal pleiotropy. Further investigation is required to explore the relationship between insulin levels and anorexia.
Telomere length and human hippocampal neurogenesis
Authors: Palmos Alish B. , Duarte Rodrigo R. R. , Smeeth Demelza M. , Hedges Erin C. , Nixon Douglas F. , Thuret Sandrine , Powell Timothy R.
Published: September 2020

Short telomere length is a risk factor for age-related disease, but it is also associated with reduced hippocampal volumes, age-related cognitive decline and psychiatric disorder risk. The current study explored whether telomere shortening might have an influence on cognitive function and psychiatric disorder pathophysiology, via its hypothesised effects on adult hippocampal neurogenesis. We modelled telomere shortening in human hippocampal progenitor cells in vitro using a serial passaging protocol that mimics the end-replication problem. Serially passaged progenitors demonstrated shorter telomeres (P ≤ 0.05), and reduced rates of cell proliferation (P ≤ 0.001), with no changes in the ability of cells to differentiate into neurons or glia. RNA-sequencing and gene-set enrichment analyses revealed an effect of cell ageing on gene networks related to neurogenesis, telomere maintenance, cell senescence and cytokine production. Downregulated transcripts in our model showed a significant overlap with genes regulating cognitive function (P ≤ 1 × 10−5), and risk for schizophrenia (P ≤ 1 × 10−10) and bipolar disorder (P ≤ 0.005). Collectively, our results suggest that telomere shortening could represent a mechanism that moderates the proliferative capacity of human hippocampal progenitors, which may subsequently impact on human cognitive function and psychiatric disorder pathophysiology.