Miracle-dz/UniFAR-FTUs huggingface dataset:
Multiplicity issues for platform trials with a shared control arm

ABSTRACT This paper provides in-depth discussion about different types of error generated in platform trials with a common control arm, and how they compare to the ones arisen from standard independent trials. We provide our views on some of the popular “myths” associated with such design, under the frequentist framework. It is found that platform trial generally performs quite well in terms of type I error rate, false discovery rate, and power. In most cases, these operating characteristics of a platform trial are comparable to or even better than running individual trials.
Mhealth interventions to improve health and quality of life related outcomes for informal dementia caregivers: A scoping review

ABSTRACT Background The devastating effects of dementia extend to the health and well-being of informal dementia caregivers. The physical and mental requirements of serving as a dementia caregiver are evidenced in the negative health effects that this population experiences. There is a present need for effective interventions to improve health and quality of life in informal dementia caregivers. Objective To investigate the health and well-being related outcomes following mHealth use in dementia caregiver and care recipient populations. Methods A scoping review was undertaken to investigate mHealth use in dementia caregivers. Searches spanning four databases yielded 172 articles. Following screening procedures, 12 articles were included for data extraction. Results Articles were organized into three major themes: social and indirect support, health education, and technology-supported monitoring. Social and indirect support apps may be valuable for caregiver stress relief, confidence, and fatigue. Health education apps were found to 1) assist with the organization of user’s health information, and 2) impact depressive symptoms. Monitoring apps provided caregivers with methods of observing both physical and emotional well-being. Conclusion Currently, the limited evidence on the usability and usefulness of mHealth within dementia caregiver populations indicates that mHealth holds promise as an intervention platform and warrants continued investigation. Abbreviations: AD: Alzheimer’s Disease; CANE: Camberwell Assessment of Need for the Elderly; CCS: Caregiver Competence Scale, CDN: COGKNOW Day Navigator; CES-D: Center for Epidemiologic Studies Depression Scale; CG: Caregivers; CQoL-AD: Carer’s Overall Quality of Life in Alzheimer’s Disease; Dx: Diagnosis; ESM: experience sampling methodology; FB: Facebook; PA: Positive Affect; Pss-14: Perceived Stress Scale; QOL: Quality of Life; RCSS: Revised Caregiving Satisfaction Scale; SSCQ: Short Sense of Competence Questionnaire
Bottom-up perceptual salience and top-down retro-cues concurrently determine state in visual working memory

Recent studies have demonstrated that in visual working memory (VWM), only items in an active state can guide attention. Further evidence has revealed that items with higher perceptual salience or items prioritised by a valid retro-cue in VWM tend to be in an active state. However, it is unclear which factor (perceptual salience or retro-cues) is more important for influencing the item state in VWM or whether the factors can act concurrently. Experiment 1 examined the role of perceptual salience by asking participants to hold two features with relatively different perceptual salience (colour vs. shape) in VWM while completing a visual search task. Guidance effects were found when either colour or both colour and shape in VWM matched one of the search distractors but not when shape matched. This demonstrated that the more salient feature in VWM can actively guide attention, while the less salient feature cannot. However, when shape in VWM was cued to be more relevant (prioritised) in Experiment 2, we found guidance effects in both colour-match and shape-match conditions. That is, both more salient but non-cued colour and less salient but cued shape could be active in VWM, such that attentional selection was affected by the matching colour or shape in the visual search task. This suggests that bottom-up perceptual salience and top-down retro-cues can jointly determine the active state in VWM.
“Our Beauty Is in Our Breasts”: A Culture-Centered Approach to Understanding Cancer Perceptions in Kwa Zulu Natal, South Africa

Breast cancer is an incapacitating physical illness. It was once reported predominantly by patients in developed countries. With the advent of globalization, it is increasingly becoming a major health concern in developing countries such as South Africa. Breast cancer researchers have continuously advocated for original studies that address this condition from a sociocultural perspective. Consequently, in this article I examine the perceptions of breast cancer patients from underprivileged parts of Kwa Zulu Natal (KZN). Thirty semi-structured interviews were conducted with Zulu women at a tertiary hospital in the region. A culture-centered approach was utilized to gauge their perceptions of life as breast cancer patients within the conservative Zulu community. The findings revealed that this ailment is generally misunderstood, which has adverse implications for the patients. Furthermore, there is a dire need for breast cancer communication interventions that can acquaint the Zulu community with this condition.
Light-Weight Student LSTM for Real-Time Wildfire Smoke Detection

As the need for wildfire detection increases, research on wildfire smoke detection combining low-cost cameras and deep learning technology is increasing. Camera-based wildfire smoke detection is inexpensive, allowing for a quick detection, and allows a smoke to be checked by the naked eye. However, because a surveillance system must rely only on visual characteristics, it often erroneously detects fog and clouds as smoke. In this study, a combination of a You-Only-Look-Once detector and a long short-term memory (LSTM) classifier is applied to improve the performance of wildfire smoke detection by reflecting on the spatial and temporal characteristics of wildfire smoke. However, because it is necessary to lighten the heavy LSTM model for real-time smoke detection, in this paper, we propose a new method for applying the teacher–student framework to deep LSTM. Through this method, a shallow student LSTM is designed to reduce the number of layers and cells constituting the LSTM model while maintaining the original deep LSTM performance. As the experimental results indicate, our proposed method achieves up to an 8.4-fold decrease in the number of parameters and a faster processing time than the teacher LSTM while maintaining a similar detection performance as deep LSTM using several state-of-the-art methods on a wildfire benchmark dataset.
The role and regulation of VEGF-mediated ERK5 activity in endothelial cells

Extracellular signal-regulated kinase 5 (ERK5) is the newest member of the mitogen- activated protein kinase (MAPK) family following the discovery of ERK1/2, JNK and p38 MAPK. ERK5 consists of an N-terminal kinase domain, similar to the other MAPK members, and a large C-terminal domain, which is unique in structure and function from the other MAPK members. ERK5 is activated in response to a multitude of extracellular stimuli, including pro-angiogenic factors in endothelial cells. The physiological importance of ERK5 was highlighted following Erk5 gene ablation in mice, where a severe disruption to cardiovascular development and loss of vascular integrity was observed, resulting in embryonic lethality. This study investigated the differences in ERK5 activation between vascular endothelial growth factor (VEGF) stimulation of primary human dermal microvascular endothelial cells (HDMECs) compared to epidermal growth factor (EGF) stimulation of HeLa (immortalised epithelial cervical cancer cell line) cells. It was discovered that in contrast to other growth factors, VEGF appeared unique in its ability to induce ERK5 phosphorylation in HDMECs, stimulating ERK5 activity via a VEGFR-2/PLCγ-dependent pathway. Utilisation of the innovative Phos-tagTM reagent in SDS-PAGE facilitated the novel discovery that VEGF was only able to induce phosphorylation of the threonine (Thr)218/tyrosine (Tyr)220 residues present within the activation loop of the kinase domain. In contrast, EGF stimulation of HeLa cells resulted in phosphorylation of ERK5 on Thr218/Tyr220 as well as additional C- terminal residues such as Thr732. It was further demonstrated that contrary to EGF, VEGF stimulation of HDMECs did not evoke a nuclear translocation of ERK5, instead, ERK5 appeared to localise to the cytoplasm and plasma membrane. The analysis of intracellular signalling pathways following treatment with small-molecule inhibitors against MAPK/ERK kinase 5 (MEK5) and ERK5 kinase activity, revealed that VEGF-mediated ERK5 activation regulated phosphorylation of AKT in HDMECs. Furthermore, with an apparent co- localisation of ERK5 and AKT in the cytoplasm and at the plasma membrane of HDMECs, it was hypothesised that the two proteins were interacting partners. Adenoviral-mediated expression of FLAG-tagged ERK5 revealed that VEGFR-2, ERK5 and AKT co- immunoprecipitated in HDMECs, suggesting the possibility of a complex between these proteins at the cell periphery following VEGF stimulation and VEGFR-2 internalisation. Taken together, this study shows that VEGF appears to induce a unique activation of ERK5 in endothelial cells, which facilitates its interaction with AKT and subsequent regulation of AKT phosphorylation, ultimately regulating endothelial cell survival.
The Importance of Self-Determination to the Quality of Life of People with Intellectual Disability: A Perspective

There is both an intuitive and theoretical link between self-determination and quality of life for people with intellectual and developmental disabilities. Theoretically, definitions of self-determination have framed the construct with regard to its contribution to a person’s overall quality of life, while theoretical frameworks of quality of life have included self-determination among the core dimensions contributing to enhanced quality of life. These theoretical linkages have been supported by research on the quality of life and self-determination of people with intellectual and developmental disabilities and the relationships between these constructs. This article provides an overview of theoretical frameworks of self-determination, their relationship with theoretical frameworks of quality of life, and research pertaining to these constructs with people with intellectual and developmental disabilities. It is concluded that self-determination and quality of life are important constructs in designing supports that enable people with intellectual and developmental disabilities and that an important means to enhance the quality of life of people with intellectual and developmental disabilities is to promote and enable people to be self-determined.
Enhancement of HIFU thermal therapy in perfused tissue models using micron-sized FTAC-stabilized PFOB-core endovascular sonosensitizers

Abstract Background High intensity focused ultrasound (HIFU) is clinically accepted for the treatment of solid tumors but remains challenging in highly perfused tissue due to the heat sink effect. Endovascular liquid-core sonosensitizers have been previously suggested to enhance the thermal energy deposition at the focal area and to lower the near-/far-field heating. We are investigating the therapeutic potential of PFOB-FTAC micro-droplets in a perfused tissue-mimicking model and postmortem excised organs. Method A custom-made in vitro perfused tissue-mimicking model, freshly excised pig kidneys (n = 3) and liver (n = 1) were perfused and subjected to focused ultrasound generated by an MR-compatible HIFU transducer. PFOB-FTAC sonosensitizers were injected in the perfusion fluid up to 0.235% v/v ratio. Targeting and on-line PRFS thermometry were performed on a 3 T MR scanner. Assessment of the fluid perfusion was performed with pulsed color Doppler in vitro and with dynamic contrast-enhanced (DCE)-MRI in excised organs. Results Our in vitro model of perfused tissue demonstrated re-usability. Sonosensitizer concentration and perfusion rate were tunable in situ. Differential heating under equivalent HIFU sonications demonstrated a dramatic improvement in the thermal deposition due to the sonosensitizers activity. Typically, the energy deposition was multiplied by a factor between 2.5 and 3 in perfused organs after the administration of micro-droplets, while DCE-MRI indicated an effective perfusion. Conclusion The current PFOB-FTAC micro-droplet sonosensitizers provided a large and sustained enhancement of the HIFU thermal deposition at the focal area, suggesting solutions for less technological constraints, lower risk for the near-/far- field heating. We also report a suitable experimental model for other MRgHIFU studies
A chromosome-level genome assembly of the woolly apple aphid, Eriosoma lanigerum (Hausmann) (Hemiptera: Aphididae)

Woolly apple aphid (WAA, Eriosoma lanigerum Hausmann) (Hemiptera: Aphididae), is a major pest of apple trees (Malus domestica, order Rosales) and is critical to the economics of the apple industry in most parts of the world. Here, we generated a chromosome-level genome assembly of WAA – representing the first genome sequence from the aphid subfamily Eriosomatinae – using a combination of 10X Genomics linked-reads and in vivo Hi-C data. The final genome assembly is 327 Mb, with 91% of the assembled sequences anchored into six chromosomes. The contig and scaffold N50 values are 158 kb and 71 Mb, respectively, and we predicted a total of 28,186 protein-coding genes. The assembly is highly complete, including 97% of conserved arthropod single-copy orthologues based on BUSCO analysis. Phylogenomic analysis of WAA and nine previously published aphid genomes, spanning four aphid tribes and three subfamilies, reveals that the tribe Eriosomatini (represented by WAA) is recovered as a sister group to Aphidini + Macrosiphini (subfamily Aphidinae). We identified syntenic blocks of genes between our WAA assembly and the genomes of other aphid species and find that two WAA chromosomes (El5 and El6) map to the conserved Macrosiphini and Aphidini X chromosome. Our high-quality WAA genome assembly and annotation provides a valuable resource for research in a broad range of areas such as comparative and population genomics, insect-plant interactions and pest resistance management.
Rehearsal of tactile working memory: Premotor cortex recruits two dissociable neuronal content representations

Recent working memory (WM) research has focused on identifying brain regions that retain different types of mental content. Only few neuroimaging studies have explored the mechanism of attention‐based refreshing, which is a type of rehearsal and is thought to implement the dynamic components of WM allowing for update of WM contents. Here, we took advantage of the distinct coding properties of the superior parietal lobe (SPL), which retains spatial layout information, and the right inferior frontal gyrus (IFG), which retains frequency information of vibrotactile stimuli during tactile WM. In an fMRI delayed match‐to‐sample task, participants had to internally rehearse sequences of spatial layouts or vibratory frequencies. Our results replicate the dissociation of SPL and IFG for the retention of layout and frequency information in terms of activation differences between conditions. Additionally, we found strong premotor cortex (PMC) activation during rehearsal of either stimulus type. To explore interactions between these regions we used dynamic causal modeling and found that activation within the network was best explained by a model that allows the PMC to drive activity in the SPL and IFG during rehearsal. This effect was content‐specific, meaning that the PMC showed stronger influence on the SPL during pattern rehearsal and stronger influence on the IFG during frequency rehearsal. In line with previously established PMC contributions to sequence processing, our results suggest that it acts as a content‐independent area that flexibly recruits content‐specific regions to bring a WM item into the focus of attention during the rehearsal of tactile stimulus sequences.
A multi-institution study: comparison of the heating patterns of five different MR-guided deep hyperthermia systems using an anthropomorphic phantom

Abstract Introduction Within the hyperthermia community, consensus exists that clinical outcome of the treatment radiotherapy and/or chemotherapy plus hyperthermia (i.e. elevating tumor temperature to 40 − 44 °C) is related to the applied thermal dose; hence, treatment quality is crucial for the success of prospective multi-institution clinical trials. Currently, applicator quality assurance (QA) measurements are implemented independently at each institution using basic cylindrical phantoms. A multi-institution comparison of heating quality using magnetic resonance thermometry (MRT) and anatomical representative anthropomorphic phantoms provides a unique opportunity to obtain novel QA insights to facilitate multi-institution trial evaluation. Objective Perform a systematic QA procedure to compare the performance of MR-compatible hyperthermia systems in five institutions. Methods and materials Anthropomorphic phantoms, including pelvic and spinal bones, were produced. Clinically relevant power of 600 watts was applied for ∼12 min to allow for 8 sequential MR-scans. The 3D-heating distribution, steering capabilities, and presence of off-target heating were analyzed. Results The evaluated devices show comparable heating profiles for centric and eccentric targets. The differences observed in the 3D-heating profiles are the result of variations in the exact phantom positioning and applicator characteristics, whereby positioning of the phantom followed current ESHO-QA guidelines. Conclusion Anthropomorphic phantoms were used to perform QA-measurements of MR-guided hyperthermia systems operating in MR-scanners of different brands. Comparable heating profiles are shown for the five evaluated institutions. Subcentimeter differences in position substantially affected the results when evaluating the heating patterns. Integration of advanced phantoms and precise positioning in QA-guidelines should be evaluated to guarantee the best quality patient care.
Cocoa (Theobroma cacao L.) Seed Proteins’ Anti-Obesity Potential through Lipase Inhibition Using In Silico, In Vitro and In Vivo Models

The aim of this study was to determine the pancreatic lipase (PL) inhibitory effect of cocoa protein (CP) hydrolysates (CPH) using in silico and in vitro approaches, and an in vivo high-fat diet (HF) obese rat model. The results showed better theoretical affinity on PL for cocoa peptides EEQR, GGER, QTGVQ, and VSTDVNIE released from vicilin and albumins (−6.5, −6.3, −6.2, and −6.1 kcal/mol, respectively). Absorption, distribution, metabolism, and excretion (ADMET) prediction showed the human intestinal absorption (HIA) capacity of orlistat and eight cocoa peptides, demonstrating that they presented a low probability of toxicity with values lower than 0.6, while the orlistat has a high probability of hepatotoxicity with a mean value of 0.9. CPH (degree of hydrolysis of 55%) inhibited PL with an IC50 (concentration needed to inhibit 50% of enzyme activity) value of 1.38 mg/mL. The intragastric administration of 150 mg CP/kg/day to rats increased total lipids and triglycerides excretion in feces, ranging from 11% to 15% compared to the HF-diet. The HF + CP-diet also significantly decreased (p < 0.05) the apparent rate of fat absorption compared with the HF group. These results suggest that CP has anti-obesity potential by inhibiting PL, thus helping to prevent the development of non-communicable diseases.
Managed Care after Acute Myocardial Infarction (MC-AMI) Reduces Total Mortality in 12-Month Follow-Up—Results from a Poland’s National Health Fund Program of Comprehensive Post-MI Care—A Population-Wide Analysis

Introduction: Advances in the acute treatment of myocardial infarction (AMI) substantially reduced in-hospital mortality, but the post-discharge prognosis is still unacceptable. The Managed Care in Acute Myocardial Infarction (MC-AMI) is a program of Poland’s National Health Fund that aims at comprehensive post-AMI care to improve long-term prognosis. The aim of the study was to assess the effect of MC-AMI on all-cause mortality in one-year follow-up. Methods: MC-AMI includes acute MI treatment, complex revascularization, cardiac rehabilitation (CR), scheduled one-year outpatient follow-up, and prevention of sudden cardiac death. In this retrospective observational study performed in a province of Silesia, Poland, we analyzed 3893 MC-AMI participants, and compared them to 6946 patients in the control group. After propensity score matching, we compared two groups of 3551 subjects each. To assess the effect of MC-AMI and other variables on mortality, we preformed a Cox regression. Results: MC-AMI was related with mortality reduction by 38% in a 12-month observation period and the effect persisted even after. Multivariable Cox regression analysis revealed MC-AMI participation to be inversely associated with 1-year mortality (HR 0.52, 95%CI 0.42–0.65, p < 0.001). Besides that, older age (HR 1.47/10 y), ST-elevation AMI (HR 1.41), heart failure (HR 2.08), diabetes (HR 1.52), and dialysis (HR 2.38) were significantly associated with the primary endpoint. Among MC-AMI components, cardiac rehabilitation (HR 0.34) and strict outpatient care (HR 0.42) are the crucial factors affecting mortality reduction. Conclusions: Participation in MC-AMI reduced 1-year mortality by 38% and the effect persisted after the program had been completed.
Effect of Limosilactobacillus reuteri LRE02–Lacticaseibacillus rhamnosus LR04 Combination on Antibiotic-Associated Diarrhea in a Pediatric Population: A National Survey

Probiotics are living microorganisms, which, upon oral ingestion, may prevent antibiotic-associated diarrhea (AAD) through the normalization of an unbalanced gastrointestinal flora. The objective of this study was to evaluate the benefits of a probiotic combination (Limosilactibacillus reuteri LRE02-DSM 23878 and Lacticaseibacillus rhamnosus LR04-DSM 16605) on the prevention of AAD in an outpatient pediatric setting. Questionnaires were delivered to pediatricians by each patient/parent during the visits after antibiotics and probiotics treatment to monitor physiological parameters. The primary outcome of both groups (probiotics and no probiotics treated) was the evaluation of the prevalence of AAD between the two groups. Evaluation of stool consistency using the Bristol Stool Scale (BSS) score was performed, as well as the evaluation of AAD duration, frequencies of daily evacuation, and the beginning of diarrhea and weight loss during AAD in both groups and related to antibiotic categories. Results indicated that probiotics, at the recommended dosage of 1.2 × 109 CFU (Colony Forming Unit) per day for 30 days, are associated with lower rates of AAD and a decreased number of days with diarrhea, independent of the type of antibiotic used. Moreover, the use of probiotics resulted in a normal stool consistency in a shorter time period, as evaluated by the BSS.