bluuebunny/crossref_metadata_2025 huggingface dataset:
Nothing to lose: a grounded theory study of patients’ and healthcare professionals’ perspectives of being involved in the consent process for oncology trials with non-curative intent
Authors: Murphy Mary , McCaughan Eilís , Carson Matthew A , Donovan Monica , Wilson Richard H , Fitzsimons Donna
Published: October 2020

Background

Clinical cancer research trials may offer little or no direct clinical benefit to participants where a cure is no longer possible. As such, the decision-making and consent process for patient participation is often challenging.

Aim

To gain understanding of how patients make decisions regarding clinical trial participation, from the perspective of both the patient and healthcare professionals involved.

Methods

In-depth, face to face interviews using a grounded theory approach. This study was conducted in a regional Cancer Centre in the United Kingdom. Of the 36 interviews, 16 were conducted with patients with cancer that had non-curative intent and 18 with healthcare professionals involved in the consent process.

Results

‘Nothing to lose’ was identified as the core category that underpinned all other data within the study. This highlighted the desperation articulated by participants, who asserted trial participation was the ‘only hope in the room’. The decision regarding participation was taken within a ‘trusting relationship’ that was important to both patients and professionals. Both were united in their ‘fight against cancer’. These two categories are critical in understanding the decision-making/consent process and are supported by other themes presented in the theoretical model.

Conclusion

This study presents an important insight into the complex and ethically contentious situation of consent in clinical trials that have non-curative intent. It confirms that patients with limited options trust their doctor and frequently hold unrealistic hopes for personal benefit. It highlights a need for further research to develop a more robust and context appropriate consent process.
Relationship between metacognitive awareness and motivation to learn in medical students
Authors: Siqueira Marina Alves Martins , Gonçalves Johnatan Padovez , Mendonça Vitor Silva , Kobayasi Renata , Arantes-Costa Fernanda Magalhães , Tempski Patricia Zen , Martins Mílton de Arruda
Published: October 2020

Background

In self-regulated learning, learning is defined as metacognitively guided, intrinsically motivated and strategic. In the context of medical education, the development of self-regulated learning can be associated with better academic and clinical performance. Hence, this report focuses on demonstrating the association between metacognitive awareness and motivation to learn among medical students in the clinical sciences portion of their education (3rd and 4th years of the medical programme) and characterizing medical students’ motivational factors.

Methods

We performed a cross-sectional study with a qualitative and quantitative approach involving medical students from the University of Sao Paulo (USP) in Brazil. We have selected validated self-report questionnaires for the evaluation of metacognition (the Schraw and Dennison Metacognitive Awareness Inventory - MAI) and motivation to learn (the Baranik, Barron and Finney Achievement Goals for a Work Domain - AGWD). MAI has two domains: knowledge about cognition and regulation of cognition. AGWD divides achievement goals into mastery approach, mastery avoidance, performance approach and performance avoidance goal orientations. We also performed a qualitative analysis based on an open-ended question: “What motivates me the most in medical training?”

Results

One hundred eighty-five students completed the questionnaires: 103 (55.67%) were men, 110 (59.45%) were in their fourth year of the medical programme, and 152 (82.16%) were up to 24 years old. Only the knowledge about cognition domain of MAI was significantly associated with motivation to learn. We found that higher scores on the knowledge about cognition domain of MAI was associated with the mastery approach goal orientation (p = 0.003, median 0.71, IQR 0.23) and that lower scores on this same domain was associated with a mastery avoidance goal orientation (p = 0.034, median 0.65, IQR 0.14). The open-ended question showed that altruism, personal satisfaction, financial feedback, personal and supportive networks and graduating were motivational factors.

Conclusions

Metacognitive awareness and motivation to learn are closely related. This association may represent a potential target for the educational process, as deans and faculty can adopt strategies focused on promoting self-regulated learning concerning students’ motivational factors. This could enhance academic outcomes and promote more enjoyable learning.
Mentoring in the clinical training of midwifery students - a focus study of the experiences and opinions of midwifery students at the Medical University of Warsaw participating in a mentoring program
Authors: Stefaniak Małgorzata , Dmoch-Gajzlerska Ewa
Published: October 2020

Background

The current system of clinical training for midwifery students in Poland is in need of considerable revision to adapt it to the global standards and the expectations of healthcare providers, healthcare users and student midwives themselves. Aim of this study was to report the experiences of midwifery students participating in a mentor-led clinical training program and their opinions of mentoring as a novel training method.

Methods

A qualitative descriptive study that used a focus group was undertaken in the period from October 2017 to June 2019. The participants were 12 s- and third-year midwifery students at the Medical University of Warsaw who at various times during the study period had their clinical training in the Department of Obstetrics, Solec Hospital in Warsaw, Poland. All students had previous experience of clinical training other than clinical mentorship. At the end of the study, a focus group interview was conducted with all 12 participants. Five questions were selected to guide the focus group discussion: Did you get any valuable learning experience during your clinical training? How did this clinical training differ from your previous clinical training? What was your experience of one-on-one mentoring? Did the mentoring program meet your expectations? What do you think could be changed to make the proposed mentor-led clinical training more effective?

Results

Four themes were identified. The study demonstrated that mentoring was perceived by the participants as an innovative and effective method of clinical training for midwifery students. All students positively evaluated the quality of the mentor-led clinical training which allowed improving their clinical skills and building new competencies. Students believed they could effectively use their clinical skills and make informed decisions in a safe and supportive clinical learning environment. They felt that their inclusion in the therapeutic team contributed to better patient care.

Conclusions

The use of innovative forms of clinical training at undergraduate level improves its effectiveness and in the future should be reflected in a high-quality maternity care. Mentoring has its advantages for both, mentor and mentee, but the main goal is to develop and improve professional competencies of the junior partner.
The use of mobile phone functionalities by patients with asthma and their desire to use for self-care purposes
Authors: Nabovati Ehsan , Farzandipour Mehrdad , Heidarzadeh Arani Marzieh , Akbari Hossein , Sharif Reihane , Anvari Shima
Published: October 2020

Background

Mobile health (mHealth) has good potential for promoting self-care in patients suffering from chronic diseases. The patients' positive attitude toward this technology is a key factor for the successful implementation. The present study was conducted to investigate the asthma patients' use of mobile phone functionalities and their desire to receive self-care services through this technology.

Methods

This survey study was conducted in Iran in 2018. The study population consisted of 146 patients suffering from asthma. The data collection tool was a questionnaire containing items on the demographic characteristics of patients, current use of mobile phone functionalities, and desire to use them for receiving self-care services. Data were analyzed using descriptive and analytical statistics.

Results

Out of the 160 questionnaires distributed, 146 (91.25%) were completed. The majority of the participants had smartphones (84.9%). Less than half of the participants occasionally used mobile phone functionalities including mobile phone calls (42.5%) and mobile Internet (40.4%) to receive asthma-related information. A significant number of the participants had never used smartphone applications (72.6%) and E-mail (66.4%) to receive asthma-related information. The participants had their greatest use of Internet search, followed by social media, to receive information about asthma symptoms, allergenic and irritating substances, medicinal therapy, and how to use therapy aids. The participants were most willing to use social media for receiving asthma information, communicating with other patients, receiving reminders about doctor's appointment, and receiving warnings about the lack of asthma control.

Conclusion

In Iran as a developing country, asthma patients use Internet search mostly to receive instructional information and are willing to use social media rather than other mobile phone functionalities to receive self-care services. These patients believe that mobile phones are appropriate for receiving instructional information and reminders.
Natriuretic peptides for the detection of diastolic dysfunction and heart failure with preserved ejection fraction—a systematic review and meta-analysis
Authors: Remmelzwaal Sharon , van Ballegooijen Adriana J. , Schoonmade Linda J. , Dal Canto Elisa , Handoko M. Louis , Henkens Michiel T. H. M. , van Empel Vanessa , Heymans Stephane R. B. , Beulens Joline W. J.
Published: October 2020

Background

An overview of the diagnostic performance of natriuretic peptides (NPs) for the detection of diastolic dysfunction (DD) and heart failure with preserved ejection fraction (HFpEF), in a non-acute setting, is currently lacking.

Methods

We performed a systematic literature search in PubMed and Embase.com (May 13, 2019). Studies were included when they (1) reported diagnostic performance measures, (2) are for the detection of DD or HFpEF in a non-acute setting, (3) are compared with a control group without DD or HFpEF or with patients with heart failure with reduced ejection fraction, (4) are in a cross-sectional design. Two investigators independently assessed risk of bias of the included studies according to the QUADAS-2 checklist. Results were meta-analysed when three or more studies reported a similar diagnostic measure.

Results

From 11,728 titles/abstracts, we included 51 studies. The meta-analysis indicated a reasonable diagnostic performance for both NPs for the detection of DD and HFpEF based on AUC values of approximately 0.80 (0.73–0.87; I2 = 86%). For both NPs, sensitivity was lower than specificity for the detection of DD and HFpEF: approximately 65% (51–85%; I2 = 95%) versus 80% (70–90%; I2 = 97%), respectively. Both NPs have adequate ability to rule out DD: negative predictive value of approximately 85% (78–93%; I2 = 95%). The ability of both NPs to prove DD is lower: positive predictive value of approximately 60% (30–90%; I2 = 99%).

Conclusion

The diagnostic performance of NPs for the detection of DD and HFpEF is reasonable. However, they may be used to rule out DD or HFpEF, and not for the diagnosis of DD or HFpEF.
Elucidation of molecular links between obesity and cancer through microRNA regulation
Authors: Dogan Haluk , Shu Jiang , Hakguder Zeynep , Xu Zheng , Cui Juan
Published: October 2020

Background

Obesity contributes to high cancer risk in humans and the mechanistic links between these two pathologies are not yet understood. Recent emerging evidence has associated obesity and cancer with metabolic abnormalities and inflammation where microRNA regulation has a strong implication.

Methods

In this study, we have developed an integrated framework to unravel obesity-cancer linkage from a microRNA regulation perspective. Different from traditional means of identifying static microRNA targets based on sequence and structure properties, our approach focused on the discovery of context-dependent microRNA-mRNA interactions that are potentially associated with disease progression via large-scale genomic analysis. Specifically, a meta-regression analysis and the integration of multi-omics information from obesity and cancers were presented to investigate the microRNA regulation in a dynamic and systematic manner.

Results

Our analysis has identified a total number of 2,143 unique microRNA-gene interactions in obesity and seven types of cancer. Common interactions in obesity and obesity-associated cancers are found to regulate genes in key metabolic processes such as fatty acid and arachidonic acid metabolism and various signaling pathways related to cell growth and inflammation. Additionally, modulated co-regulations among microRNAs targeting the same functional processes were reflected through the analysis.

Conclusion

We demonstrated the statistical modeling of microRNA-mediated gene regulation can facilitate the association study between obesity and cancer. The entire framework provides a powerful tool to understand multifaceted gene regulation in complex human diseases that can be generalized in other biomedical applications.
Correction to: Virotheranostics, a double-barreled viral gun pointed toward cancer; ready to shoot?
Authors: Keshavarz Mohsen , Sabbaghi Ailar , Miri Seyed Mohammad , Rezaeyan Abolhasan , Arjeini Yaser , Ghaemi Amir
Published: October 2020

An amendment to this paper has been published and can be accessed via the original article.
Health systems readiness and quality of inpatient malaria case-management in Kano State, Nigeria
Authors: Ojo Abiodun A. , Maxwell Kolawole , Oresanya Olusola , Adaji Justice , Hamade Prudence , Tibenderana James K. , Abubakar Saddiq S. , Audu Bala M. , Njidda Ahmad , Gubio Aishatu B. , Snow Robert W. , Zurovac Dejan
Published: October 2020

Background

Nigeria was among the first African countries to adopt and implement change of treatment policy for severe malaria from quinine to artesunate. Seven years after the policy change health systems readiness and quality of inpatient malaria case-management practices were evaluated in Kano State of Nigeria.

Methods

A cross-sectional survey was undertaken in May 2019 at all public hospitals. Data collection comprised hospital assessments, interviews with inpatient health workers and data extraction from medical files for all suspected malaria patients admitted to the paediatric and medical wards in April 2019. Descriptive analyses included 22 hospitals, 154 health workers and 1,807 suspected malaria admissions analysed from malaria test and treat case-management perspective.

Results

73% of hospitals provided malaria microscopy, 27% had rapid diagnostic tests and 23% were unable to perform any parasitological malaria diagnosis. Artemisinin-based combination therapy (ACT) was available at 96% of hospitals, artemether vials at 68% while injectable quinine and artesunate were equally stocked at 59% of hospitals. 32%, 21% and 15% of health workers had been exposed to relevant trainings, guidelines and supervision respectively. 47% of suspected malaria patients were tested while repeat testing was rare (7%). 60% of confirmed severe malaria patients were prescribed artesunate. Only 4% of admitted non-severe test positive cases were treated with ACT, while 76% of test negative patients were prescribed an anti-malarial. Artemether was the most common anti-malarial treatment for non-severe test positive (55%), test negative (43%) and patients not tested for malaria (45%). In all categories of the patients, except for confirmed severe cases, artemether was more commonly prescribed for adults compared to children. 44% of artesunate-treated patients were prescribed ACT follow-on treatment. Overall compliance with test and treat policy for malaria was 13%.

Conclusions

Translation of new treatment policy for severe malaria into inpatient practice is compromised by lack of malaria diagnostics, stock-outs of artesunate and suboptimal health workers’ practices. Establishment of the effective supply chain and on-going supportive interventions for health workers accompanied with regular monitoring of the systems readiness and clinical practices are urgently needed.
A modified microchip-based flow chamber system for evaluating thrombogenicity in patients with thrombocytopenia
Authors: Atari Bengo , Ito Takashi , Nagasato Tomoka , Ohnishi Tomoko , Hosokawa Kazuya , Yasuda Tomotsugu , Maruyama Ikuro , Kakihana Yasuyuki
Published: October 2020

Background

In the intensive care unit (ICU), patients with thrombocytopenia are at high risk for bleeding and should be assessed for their thrombogenic potential. However, the analytical conditions of conventional hemostatic tests are unsuitable for the evaluation of low-platelet samples. Here we aimed to establish suitable analytical conditions with the Total Thrombus-formation Analysis System (T-TAS) for quantitative assessment of thrombogenic potential in patients with thrombocytopenia and to investigate how T-TAS values relate to bleeding symptoms and the effects of platelet transfusion.

Methods

Modified chips with a different chamber depth were developed for the analysis of low-platelet samples in the T-TAS. We included 10 adult patients admitted to the ICU of Kagoshima University Hospital who required platelet transfusion. Patients were divided into major and minor bleeding groups according to their bleeding scale before platelet transfusion. The thrombogenic potential of these patients before and after platelet transfusion was assessed with hemostatic function tests, including rotational thromboelastometry, multiplate aggregometry, and the T-TAS.

Results

Analysis of low-platelet samples revealed that, compared with the conventional chip (80-μm-deep chamber), the modified chip (50-μm-deep chamber) achieved higher sensitivity in detecting elevation of flow pressure caused by growth of an occlusive thrombus in the T-TAS analytical chamber. All patients in the minor bleeding group retained thrombogenic potential that occluded the modified chip (occlusion time 16.3 ± 3.3 min), whereas most patients in the major bleeding group were unable to occlude the modified chip during the 30-min measurement (P <  0.01). The recovery of thrombogenic potential after platelet transfusion was confirmed with the T-TAS and correlated with the function, rather than the count, of transfused platelets. Among all evaluated parameters in hemostatic function tests, only the T-TAS showed significant differences in occlusion time and area under the curve both between the minor and major bleeding groups and between pre- and post-platelet transfusion.

Conclusions

We developed a modified microchip-based flow chamber system that reflects the hemostatic function of patients with thrombocytopenia.
Building an enabling environment and responding to resistance to sexuality education programmes: experience from Jharkhand, India
Authors: Plesons Marina , Khanna Aarushi , Ziauddin Mohammed , Gogoi Aparajita , Chandra-Mouli Venkatraman
Published: October 2020

Background

Despite the substantial need for sexuality education and evidence on its effectiveness, implementing organisations continue to grapple with numerous challenges, especially related to community support and resistance. This article aims to analyse the experience ofUdaan,a programme that has achieved remarkable success in Jharkhand, India, to answer the following questions: (1) What strategies didUdaanuse to create a supportive environment? and (2) What processes didUdaanuse to respond to resistance during its implementation?

Methods

We reviewed programme documents and publications, synthesized key themes, identified questions of interest, and conducted interviews with key informants from the Centre for Catalyzing Change’s leadership.

Results

Community support forUdaanwas built by ensuring that the curriculum was responsive to the context, capitalizing on an enabling policy environment, institutionalizingUdaanthrough government-led implementation, prioritizing careful selection and training of teachers, emphasizing monitoring and evaluation, and engaging with community gatekeepers.Udaaneffectively responded to resistance by organizing a formal curriculum review, orienting editors of local newspapers on the programme; responding to questions and concerns; and proactively creating positive visibility.

Conclusion

The lessons fromUdaanprovide insight into approaches that can be used to design and sustain sexuality education programmes in complex settings.
Building capacity in dissemination and implementation science: a systematic review of the academic literature on teaching and training initiatives
Authors: Davis Rachel , D’Lima Danielle
Published: October 2020

Background

The field of dissemination and implementation (D&I) science has grown significantly over recent years. Alongside this, an increased demand for training in D&I from researchers and implementers has been seen. Research describing and evaluating D&I training opportunities, referred to here as ‘capacity building initiatives’ (CBIs), can help provide an understanding of different methods of training as well as training successes and challenges. However, to gain a more detailed understanding of the evidence-base and how D&I CBIs are being reported in publications, a field-wide examination of the academic literature is required.

Methods

Systematic review to identify the type and range of D&I CBIs discussed and/or appraised in the academic literature. EMBASE, Medline and PsycINFO were searched between January 2006 and November 2019. Articles were included if they reported on a D&I CBI that was developed by the authors (of each of the included articles) or the author’s host institution. Two reviewers independently screened the articles and extracted data using a standardised form.

Results

Thirty-one articles (from a total of 4181) were included. From these, 41 distinct D&I CBIs were identified which focussed on different contexts and professions, from 8 countries across the world. CBIs ranged from short courses to training institutes to being part of academic programmes. Nearly half were delivered face-face with the remainder delivered remotely or using a blended format. CBIs often stipulated specific eligibility criteria, strict application processes and/or were oversubscribed. Variabilities in the way in which the D&I CBIs were reported and/or evaluated were evident.

Conclusions

Increasing the number of training opportunities, as well as broadening their reach (to a wider range of learners), would help address the recognised deficit in D&I training. Standardisation in the reporting of D&I CBIs would enable the D&I community to better understand the findings across different contexts and scientific professions so that training gaps can be identified and overcome. More detailed examination of publications on D&I CBIs as well as the wider literature on capacity building would be of significant merit to the field.
Electroencephalographic features in patients undergoing extracorporeal membrane oxygenation
Authors: Peluso Lorenzo , Rechichi Serena , Franchi Federico , Pozzebon Selene , Scolletta Sabino , Brasseur Alexandre , Legros Benjamin , Vincent Jean-Louis , Creteur Jacques , Gaspard Nicolas , Taccone Fabio Silvio
Published: October 2020

Background

Neurologic injury is one of the most frequent causes of death in patients undergoing extracorporeal membrane oxygenation (ECMO). As neurological examination is often unreliable in sedated patients, additional neuromonitoring is needed. However, the value of electroencephalogram (EEG) in adult ECMO patients has not been well assessed. Therefore, the aim of this study was to assess the occurrence of electroencephalographic abnormalities in patients treated with extracorporeal membrane oxygenation (ECMO) and their association with 3-month neurologic outcome.

Methods

Retrospective analysis of all patients undergoing venous–venous (V–V) or venous–arterial (V–A) ECMO with a concomitant EEG recording (April 2009–December 2018), either recorded intermittently or continuously. EEG background was classified into four categories: mild/moderate encephalopathy (i.e., mostly defined by the presence of reactivity), severe encephalopathy (mostly defined by the absence of reactivity), burst-suppression (BS) and suppressed background. Epileptiform activity (i.e., ictal EEG pattern, sporadic epileptiform discharges or periodic discharges) and asymmetry were also reported. EEG findings were analyzed according to unfavorable neurological outcome (UO, defined as Glasgow Outcome Scale < 4) at 3 months after discharge.

Results

A total of 139 patients (54 [41–62] years; 60 (43%) male gender) out of 596 met the inclusion criteria and were analyzed. Veno–arterial (V–A) ECMO was used in 98 (71%); UO occurred in 99 (71%) patients. Continuous EEG was performed in 113 (81%) patients. The analysis of EEG background showed that 29 (21%) patients had severe encephalopathy, 4 (3%) had BS and 19 (14%) a suppressed background. In addition, 11 (8%) of patients had seizures or status epilepticus, 10 (7%) had generalized periodic discharges or lateralized periodic discharges, and 27 (19%) had asymmetry on EEG. In the multivariate analysis, the occurrence of ischemic stroke or intracranial hemorrhage (OR 4.57 [1.25–16.74]; p = 0.02) and a suppressed background (OR 10.08 [1.24–82.20]; p = 0.03) were independently associated with UO. After an adjustment for covariates, an increasing probability for UO was observed with more severe EEG background categories.

Conclusions

In adult patients treated with ECMO, EEG can identify patients with a high likelihood of poor outcome. In particular, suppressed background was independently associated with unfavorable neurological outcome.
Stuck-moving needle acupuncture myofascial trigger point to treat idiopathic frozen shoulder: study protocol for a randomized controlled trial
Authors: Bai Yang , Wang Ying , Chen Bo , Qin Yinan , Lei Qianqian , Zhao Hailong , Lu Jingbao , Fan Qian , Wang Yali , Song Hongbo , Cheng Maomao , Wang Wei , Hu Shengen , Du Yuan Hao , Xia Tian
Published: October 2020

Background

There are evidence for the efficacy of acupuncture treatment for chronic shoulder pain, however, it remains unclear the best acupuncture modes for effective treatment. We compared the effect of the myofascial trigger point (MTrp) stuck-moving needle acupuncture with that of common acupuncture treatments. Further, we evaluated the efficacy and safety of stuck-moving needle acupuncture for the MTrp in improving pain and range of motions in patients with idiopathic frozen shoulder. The aim of present study is to select an effective therapy for patients with idiopathic frozen shoulder.

Methods

Randomized controlled trial will be conducted in the three clinical centers of Qingyang Traditional Chinese Medicine Hospital, Qingyang Xifeng district People’s Hospital, and Qingyang Second People’s Hospital in China from February 2020 to January 2021. One hundred and eight frozen shoulder patients will be recruited and randomized into one of three groups in a 1:1:1 ratio of the stuck-moving needle acupuncture group, common acupuncture control group, and physical exercise control group. This trial will include a 1-week baseline period, a 3-week treatment period, and a 12-week follow-up period. During the 3 weeks of the treatment period, patients will receive nine sessions of acupuncture. The primary outcome will be related to change in the Visual Analogue Scale (VAS) and measurement of range of joint motion (ROM) from the baseline period to the 12-week follow-up period. Secondary outcome measures will include measurement of pressure pain threshold (PPT), pressure pain tolerance (PTT), Oxford Shoulder Score (OSS), 36-item short form survey, and patient satisfaction evaluation. Adverse events also will be recorded for safety assessment.

Discussion

The results of this trial will allow us to compare the difference in efficacy between stuck-moving needle acupuncture MTrP with that of common acupuncture treatments. The findings from this trial will be published in the peer-reviewed journals.

Trial registration

Acupuncture-Moxibustion Clinical Trial Registry (ChiMCTR1900002862) and Chinese Clinical Trial Registry (ChiCTR1900028452). Registered on 22 December 2019. http://www.chictr.org.cn/showproj.aspx?proj=47354
Existence and uniqueness results for fractional Navier boundary value problems
Authors: Bachar Imed , Eltayeb Hassan
Published: October 2020

We establish the existence, uniqueness, and positivity for the fractional Navier boundary value problem:
$$\begin{aligned} \textstyle\begin{cases} D^{\alpha }(D^{\beta }\omega )(t)=h(t,\omega (t),D^{\beta }\omega (t)), & 0< t< 1, \\ \omega (0)=\omega (1)=D^{\beta }\omega (0)=D^{\beta }\omega (1)=0, \end{cases}\displaystyle \end{aligned}$$

{

D
α

(

D
β

ω
)
(
t
)
=
h
(
t
,
ω
(
t
)
,

D
β

ω
(
t
)
)
,

0
<
t
<
1
,

ω
(
0
)
=
ω
(
1
)
=

D
β

ω
(
0
)
=

D
β

ω
(
1
)
=
0
,

where $\alpha,\beta \in (1,2]$
α
,
β
∈
(
1
,
2
]
, $D^{\alpha }$

D
α

and $D^{\beta }$

D
β

are the Riemann–Liouville fractional derivatives. The nonlinear real function h is supposed to be continuous on $[0,1]\times \mathbb{R\times R}$
[
0
,
1
]
×

R
×
R

and satisfy appropriate conditions. Our approach consists in reducing the problem to an operator equation and then applying known results. We provide an approximation of the solution. Our results extend those obtained in (Dang et al. in Numer. Algorithms 76(2):427–439, 2017) to the fractional setting.
Multi-scale habitat selection and impacts of climate change on the distribution of four sympatric meso-carnivores using random forest algorithm
Authors: Rather Tahir Ali , Kumar Sharad , Khan Jamal Ahmad
Published: October 2020

Background

The habitat resources are structured across different spatial scales in the environment, and thus animals perceive and select habitat resources at different spatial scales. Failure to adopt the scale-dependent framework in species habitat relationships may lead to biased inferences. Multi-scale species distribution models (SDMs) can thus improve the predictive ability as compared to single-scale approaches. This study outlines the importance of multi-scale modeling in assessing the species habitat relationships and may provide a methodological framework using a robust algorithm to model and predict habitat suitability maps (HSMs) for similar multi-species and multi-scale studies.

Results

We used a supervised machine learning algorithm, random forest (RF), to assess the habitat relationships of Asiatic wildcat (Felis lybica ornata), jungle cat (Felis chaus), Indian fox (Vulpes bengalensis), and golden-jackal (Canis aureus) at ten spatial scales (500–5000 m) in human-dominated landscapes. We calculated out-of-bag (OOB) error rates of each predictor variable across ten scales to select the most influential spatial scale variables. The scale optimization (OOB rates) indicated that model performance was associated with variables at multiple spatial scales. The species occurrence tended to be related strongest to predictor variables at broader scales (5000 m). Multivariate RF models indicated landscape composition to be strong predictors of the Asiatic wildcat, jungle cat, and Indian fox occurrences. At the same time, topographic and climatic variables were the most important predictors determining the golden jackal distribution. Our models predicted range expansion in all four species under future climatic scenarios.

Conclusions

Our results highlight the importance of using multiscale distribution models when predicting the distribution and species habitat relationships. The wide adaptability of meso-carnivores allows them to persist in human-dominated regions and may even thrive in disturbed habitats. These meso-carnivores are among the few species that may benefit from climate change.
Maintaining the balance of TDP-43, mitochondria, and autophagy: a promising therapeutic strategy for neurodegenerative diseases
Authors: Huang Chunhui , Yan Sen , Zhang Zaijun
Published: October 2020

Mitochondria are the energy center of cell operations and are involved in physiological functions and maintenance of metabolic balance and homeostasis in the body. Alterations of mitochondrial function are associated with a variety of degenerative and acute diseases. As mitochondria age in cells, they gradually become inefficient and potentially toxic. Acute injury can trigger the permeability of mitochondrial membranes, which can lead to apoptosis or necrosis. Transactive response DNA-binding protein 43 kDa (TDP-43) is a protein widely present in cells. It can bind to RNA, regulate a variety of RNA processes, and play a role in the formation of multi-protein/RNA complexes. Thus, the normal physiological functions of TDP-43 are particularly important for cell survival. Normal TDP-43 is located in various subcellular structures including mitochondria, mitochondrial-associated membrane, RNA particles and stress granules to regulate the endoplasmic reticulum–mitochondrial binding, mitochondrial protein translation, and mRNA transport and translation. Importantly, TDP-43 is associated with a variety of neurodegenerative diseases, including amyotrophic lateral sclerosis, frontotemporal dementia and Alzheimer's disease, which are characterized by abnormal phosphorylation, ubiquitination, lysis or nuclear depletion of TDP-43 in neurons and glial cells. Although the pathogenesis of TDP-43 proteinopathy remains unknown, the presence of pathological TDP-43 inside or outside of mitochondria and the functional involvement of TDP-43 in the regulation of mitochondrial morphology, transport, and function suggest that mitochondria are associated with TDP-43-related diseases. Autophagy is a basic physiological process that maintains the homeostasis of cells, including targeted clearance of abnormally aggregated proteins and damaged organelles in the cytoplasm; therefore, it is considered protective against neurodegenerative diseases. However, the combination of abnormal TDP-43 aggregation, mitochondrial dysfunction, and insufficient autophagy can lead to a variety of aging-related pathologies. In this review, we describe the current knowledge on the associations of mitochondria with TDP-43 and the role of autophagy in the clearance of abnormally aggregated TDP-43 and dysfunctional mitochondria. Finally, we discuss a novel approach for neurodegenerative treatment based on the knowledge.
Physiological and transcriptome changes induced by exogenous putrescine in anthurium under chilling stress
Authors: Sun Xiangli , Yuan Zebin , Wang Bo , Zheng Liping , Tan Jianzhong , Chen Fadi
Published: October 2020

Background

Chilling stress is the major factor limiting plant productivity and quality in most regions of the world. In the present study, we aimed to evaluate the effects of putrescine (Put) and polyamine inhibitor d-arginine (d-arg) on the chilling tolerance of anthurium (Anthurium andraeanum).

Results

Anthurium seedlings were pretreated with five different concentrations of Put solution or d-arg solution. Subsequently, the seedlings were subjected to chilling stress at 6 °C for 3 days, followed by a recovery at 25 °C for 1 day. Relative permeability of the plasma membrane, as well as physiological and morphologic parameters was assessed during the experiments. Additionally, transcriptome sequencing and patterns of differential gene expression related to chilling response were analyzed by qRT-PCR in 1.0 mM Put-treated and untreated anthurium seedlings. Results indicated that the supplementation of exogenous Put decreased the extent of membrane lipid peroxidation and the accumulation of malondialdehyde (MDA), promoted the antioxidant activities and proline content and maintained the morphologic performances compared with the control group. This finding indicated that the application of exogenous Put could effectively decrease the injury and maintain the quality of anthurium under chilling conditions. In contrast, the treatment of d-arg exhibited the opposite effects, which confirmed the effects of Put.

Conclusions

This research provided a possible approach to enhance the chilling tolerance of anthurium and reduce the energy consumption used in anthurium production.
Efficacy of low-dose local clindamycin in different times for microbial decontamination of autogenous particulate bone graft
Authors: Mohajerani Hassan , Irajian Gholamreza , Latifi Fatemeh , Masjedian Faramarz , Tabrizi Reza
Published: October 2020

Background

Clindamycin in low concentration (20 μg/mL) is safe for vitality and osteogenic potential of bone cells. The aim of this study was to evaluate the efficacy of local clindamycin (20 μg/mL) in two different exposure times, for microbial decontamination of particulate bone graft, collected during implant site preparation.

This non-randomized parallel-group study was conducted on samples from 17 patients. The particulate bone collected during implant site preparation was divided into three portions by weight: in group S1, the particulate bone was immersed in thioglycolate broth without any antibiotic treatment; in group S2, the collected particulate bone was irrigated with 100 mL clindamycin solution (20 μg/mL); and in group S3, the collected particulate bone was soaked in one ml clindamycin solution (20 μg/mL) for 3 min. Samples in the three groups were cultured in aerobic and anaerobic media and species and CFU count of isolated bacteria were determined.

Results

Analysis of the data demonstrated a significant difference among the three groups in the mean count of total microorganisms (P = 0.001). The difference in the mean count of anaerobic and aerobic microorganisms in the three groups was statistically significant as well (P = 0.001). Pseudomonas aeruginosa was the only microorganism that was not affected with the mentioned antibiotic.

Conclusions

Local use of low-dose clindamycin (20 μg/mL)—irrigation or 3 min immersing—is effective for the decontamination of particulate bone grafts.
nSARS-Cov-2, pulmonary edema and thrombosis: possible molecular insights using miRNA-gene circuits in regulatory networks
Authors: Khurana P. , Gupta A. , Sugadev R. , Sharma Y. K. , Varshney R. , Ganju L. , Kumar B.
Published: October 2020

Background

Given the worldwide spread of the novel Severe Acute Respiratory Syndrome Coronavirus 2 (nSARS-CoV-2) infection pandemic situation, research to repurpose drugs, identify novel drug targets, vaccine candidates have created a new race to curb the disease. While the molecular signature of nSARS-CoV-2 is still under investigation, growing literature shows similarity among nSARS-CoV-2, pulmonary edema, and thromboembolic disorders due to common symptomatic features. A network medicine approach is used to to explore the molecular complexity of the disease and to uncover common molecular trajectories of edema and thrombosis with nSARS-CoV-2.

Results and conclusion

A comprehensive nSARS-CoV-2 responsive miRNA: Transcription Factor (TF): gene co-regulatory network was built using host-responsive miRNAs and it’s associated tripartite, Feed-Forward Loops (FFLs) regulatory circuits were identified. These regulatory circuits regulate signaling pathways like virus endocytosis, viral replication, inflammatory response, pulmonary vascularization, cell cycle control, virus spike protein stabilization, antigen presentation, etc. A unique miRNA-gene regulatory circuit containing a consortium of four hub FFL motifs is proposed to regulate the virus-endocytosis and antigen-presentation signaling pathways. These regulatory circuits also suggest potential correlations/similarity in the molecular mechanisms during nSARS-CoV-2 infection, pulmonary diseases and thromboembolic disorders and thus could pave way for repurposing of drugs. Some important miRNAs and genes have also been proposed as potential candidate markers. A detailed molecular snapshot of TGF signaling as the common pathway, that could play an important role in controlling common pathophysiologies among diseases, is also put forth.
The use of patient-reported outcomes to detect adverse events in metastatic melanoma patients receiving immunotherapy: a randomized controlled pilot trial
Authors: Tolstrup Lærke K. , Bastholt Lars , Dieperink Karin B. , Möller Sören , Zwisler Ann-Dorthe , Pappot Helle
Published: October 2020

Background

A randomized controlled pilot trial was conducted to assess if melanoma patients treated with immunotherapy had the number of grade 3 or 4 adverse events during treatment reduced by 50% using a tailored electronic patient-reported outcomes tool in addition to standard toxicity monitoring compared to standard monitoring alone. Secondary endpoints were: if more AEs were reported in the intervention group, if there was a difference between the two groups in the number of telephone consultations, extra out-patient visits, number of days in the hospital, days in steroid treatment and the time patients experienced grade 2 or higher toxicity.

Patients and methods

Melanoma patients receiving immunotherapy at the Department of Oncology, Odense University Hospital, Denmark participated. Standard care included assessment of AEs by a clinician before each treatment cycle using the Common Terminology Criteria for Adverse Events. In addition, patients randomized to the intervention reported their AEs weekly by an electronic PRO-tool based on the PRO-CTCAE platform.

Results

One hundred forty-six melanoma patients were randomized. In this study, we did not detect a difference between the two groups in the number of grade 3 or 4 AEs (P = 0.983), in the overall number of AEs (P = 0.560) or in the time the patients in the two groups experienced grade 2 or higher toxicity (0.516). The number of phone contacts was significantly higher in the intervention group (P = 0.009) and there was a tendency towards patients in the intervention group having more extra visits (P = 0.156).

Conclusion

It has been examined if the number of severe AEs for melanoma patients receiving immunotherapy could be reduced by involving the patients in the reporting of symptoms. The results do not justify the expansion of the pilot study into a regular phase III study with this particular set-up. However, a significant difference in the number of phone contacts was found as patients in the intervention group called more frequently, indicating that their attention to AEs was increased. Even though the use of an electronic PRO tool could not reduce the number of severe AEs in this melanoma population, a positive impact on other endpoints such as QoL, communication, or treatment-planning, cannot be excluded.

Trial registration

Clinicaltrials.gov NCT03073031 Registered 8 March 2017, Retrospectively registered.
Whole-exome sequencing and homozygosity mapping identify variants in NCOR1 and MAP2K3 associated with non-syndromic congenital heart defects
Authors: Gholipoorfeshkecheh Rahim , Agarwala Swati , G Kavya , Krishnappa Santhosh , Savitha Mysore R. , Ramachandra Nallur B.
Published: October 2020

Background

Homozygosity mapping is an efficient gene mapping method applicable to recessive disorders. It can detect homozygous segments of identical haplotype structures shared at a higher frequency among ventricular septal defect (VSD) and tetralogy of Fallot (TOF) cases. This study aims to identify the recessive genes involved in congenital heart disease (CHD) cases by homozygosity mapping. A total of 36 CHD cases of Indian origin were recruited based on inclusion and exclusion criteria, disease severity, and hole size. Of these, ten prediagnosed VSD and TOF cases were selected for homozygosity mapping. For in silico validation of variations, overlapping gene variants were analyzed from 26 cases based on pathogenecity and haploinsufficiency scores.

Results

Genome-wide homozygosity mapping identified 34 homozygous regions with a maximum block length of 80 bp marked for the CHD samples under study. A total of 4863 genes were identified in these 34 homozygous regions, which were present across almost all chromosomes except chromosomes 4, 8, 12, and 13. The homozygosity region found in chromosome 17 revealed genes for CHD manifestation. This homozygous region contained VSD- and TOF-related genes—Nuclear Corepressor 1 (NCOR1) and Mitogen-Activated Protein Kinase Kinase 3 (MAP2K3). In silico validation identified damaging variants for NCOR1 and MAP2K3. Three variants, G207C, C241T, and G244A, were found on exon 2 in the transcript NM_001190438 for NCOR1. Three variants were also found for MAP2K3, namely G194T and C199T in exon 5 and C578T in exon 8 in the transcript NM_002756. All these variants were present in the protein kinase domain.

Conclusion

Presence of homozygous regions identifies recessive genes leading to disease severity. Defects in recessive genes NCOR1 and MAP2K3 are responsible for abnormal myogenesis, resulting in CHD manifestation.
Prospective associations between ECG abnormalities and death or myocardial infarction in a cohort of 980 employed, middle-aged Swedish men
Authors: Dimberg Lennart , Eriksson Bo , Enqvist Per
Published: October 2020

Background

In 1993, 1000 randomly selected employed Swedish men aged 45–50 years were invited to a nurse-led health examination with a survey on life style, fasting lab tests, and a 12-lead ECG. A repeat examination was offered in 1998. The ECGs were classified according to the Minnesota Code. Upon ethical approval, endpoints in terms of MI and death over 25 years were collected from Swedish national registers with the purpose of analyzing the independent association of ECG abnormalities as risk factors for myocardial infarction and death.

Results

Seventy-nine of 977 participants had at least one ECG abnormality 1993 or 1998.

One hundred participants had a first MI over the 25 years. Odds ratio for having an MI in the group that had one or more ECG abnormality compared with the group with two normal ECGs was estimated to 3.16. 95%CI (1.74; 5.73), p value 0.0001.

One hundred fifty-seven participants had died before 2019. For death, similarly no statistically significant difference was shown, OR 1.52, 95%CI (0.83; 2.76).

Conclusions

Our study suggests that presence of ST- and R-wave changes is associated with an independent 3–4-fold increased risk of MI after 25 years follow-up, but not of death. A 12-lead resting ECG should be included in any MI risk calculation on an individual level.
Debt sustainability and the fiscal reaction function: evidence from MIST countries
Authors: Ogbeifun Lawrence , Shobande Olatunji
Published: October 2020

The use of public debt is not new in financing developmental objectives. A significant challenge arose when it became obvious that the indebted countries could not fulfill its existing financial obligation to the rest of the world where debt is sourced. For a panel of 4 heterogeneous countries from 1990 to 2017, we study governments’ reactions to debt accumulation and the corrective measures taken when its borrowings result in a rise in debt–GDP ratio. The study evidence is based on the fixed effect and the feasible generalized least squares estimators. We find evidence that primary balance improves by about 0.005–0.013 for every 1 percentage point increase in central government debt after controlling for other relevant factors. The results further suggest that the accrued interest payments on debt reflect the effective debt management policies across the countries, whereas the activities on the current account balance impose a possible threat to the primary balance. The study calls for policies that increase fiscal bases through the reduction in fiscal expenditure and the reinforcement of tax base revenue across the MIST countries.