Miracle-dz/UniFAR-FTUs huggingface dataset:
Passing on wisdom: exploring the end-of-life wishes of Aboriginal people from the Midwest of Western Australia.

INTRODUCTION Indigenous patients with life-limiting conditions have complex needs, experience reduced access to and uptake of treatment, and have lower utilisation of palliative care services than the general population. Lack of understanding of the role of palliative care and poor availability of culturally safe specialist palliative care services impact on Indigenous people's end-of-life decision-making. METHODS To understand Aboriginal people's perspectives and experiences at the end of life, an exploratory study using facilitated group discussions in community settings in a region of Western Australia was undertaken. Local Aboriginal people were engaged to talk frankly about their wishes and concerns around end of life. The community consultations included two meetings at the local Aboriginal corporation, an evening meeting for invited community members, a meeting at the local Aboriginal community controlled health service and two further meetings of community members at local gathering places. These were supplemented by the analysis of previous in-depth video-recorded interviews that were undertaken with Aboriginal people with cancer reporting on their concerns and wishes. RESULTS The community consultations raised considerable discussion about wills, where to die, burial versus cremation, and the cost of funerals. Possibilities emerging from participants' reflections on the issue were public celebrations to honour someone's life, the potential use of sorting cards to help discussions about end-of-life personal wishes, and interest in making and decorating coffins. Aboriginal people with cancer raised similar issues, and focused on avoiding family disharmony by ensuring their family were aware of their end-of-life wishes. CONCLUSION Within a safe space, Aboriginal people were happy to talk about end-of-life wishes, although certain aspects of death remain contentious. Sorting cards, ceremonies, education and care roles involving Aboriginal people offer potential means for effectively engaging Aboriginal people in preparing for death and dealing with grief.
Adolescent Hyperuricemia with Lipid Storage Myopathy: A Clinical Study

Background In this study, we investigated the clinical and pathological features of patients with lipid storage myopathy (LSM) complicated with hyperuricemia, to improve clinicians’ understanding of metabolic multi-muscular disorder with metabolic disorders, and to reduce the risk of missed diagnosis of LSM. Material/Methods From January 2005 to December 2017, 8 patients underwent muscle biopsy and diagnosed by muscle pathology and genetic testing in our hospital. All 8 patients were in compliance with LSM diagnosis. We collected data on the patient’s clinical performance, adjuvant examination, treatment, and outcomes to provide a comprehensive report and description of LSM patients with hyperuricemia. Results All patients were diagnosed as having ETFDH gene mutations. The main clinical manifestations of patients were chronic limb and trunk weakness, limb numbness, and muscle pain. The serum creatine kinase (CK) values in all patients were higher than normal values. Electromyography showed 3 cases of simple myogenic damage and 3 cases of neurogenic injury. Hematuria metabolic screening showed that 2 patients had elevated glutaric aciduria, and 1 patient had elevated fatty acyl carnitine in the blood. All patients were given riboflavin treatment, and the clinical symptoms were significantly improved, and 3 patients returned to normal uric acid levels after treatment. Pathological staining showed an abnormal deposition of lipid droplets in muscle fibers. Conclusions If an adolescent hyperuricemia patient has abnormal limb weakness, exercise intolerance, and elevated serum CK values, clinicians need to be highly alert to the possibility of LSM. Early diagnosis and treatment of LSM should improve the clinical symptoms and quality of life and reduce complications.
Targeting FAT1 Inhibits Carcinogenesis, Induces Oxidative Stress and Enhances Cisplatin Sensitivity through Deregulation of LRP5/WNT2/GSS Signaling Axis in Oral Squamous Cell Carcinoma

FAT atypical cadherin 1 (FAT1) regulates cell-cell adhesion and extracellular matrix architecture, while acting as tumor suppressor or oncogene, context-dependently. Despite implication of FAT1 in several malignancies, its role in oral squamous cell carcinoma (OSCC) remains unclear. Herein, we document the driver-oncogene role of FAT1, and its mediation of cell-death evasion, proliferation, oncogenicity, and chemoresistance in OSCC. In-silica analyses indicate FAT1 mutations are frequent and drive head-neck SCC, with enhanced expression defining high-risk population and poor prognosis. We demonstrated aberrant FAT1 mRNA and protein expression in OSCC compared with non-cancer tissues, whereas loss-of-FAT1-function attenuates human primary SAS and metastatic HSC-3 OSCC cell viability, without affecting normal primary human gingival fibroblast cells. shFAT1 suppressed PCNA and upregulated BAX/BCL2 ratio in SAS and HSC-3 cells. Moreover, compared with wild-type cells, shFAT1 concomitantly impaired HSC-3 cell migration, invasion, and clonogenicity. Interestingly, while over-expressed FAT1 characterized cisplatin-resistance (CispR), shFAT1 synchronously re-sensitized CispR cells to cisplatin, enhanced glutathione (GSH)/GSH synthetase (GSS)-mediated oxidative stress and deregulated LRP5/WNT2 signaling. Concisely, FAT1 is an actionable driver-oncogene in OSCC and targeting FAT1 in patients with erstwhile cisplatin-resistant OSCC is therapeutically promising.
Decrease of miR-19b-3p in Brain Microvascular Endothelial Cells Attenuates Meningitic Escherichia coli-Induced Neuroinflammation via TNFAIP3-Mediated NF-κB Inhibition

Meningitic Escherichia coli can traverse the host’s blood–brain barrier (BBB) and induce severe neuroinflammatory damage to the central nervous system (CNS). During this process, the host needs to reasonably balance the battle between bacteria and brain microvascular endothelial cells (BMECs) to minimize inflammatory damage, but this quenching of neuroinflammatory responses at the BBB is unclear. MicroRNAs (miRNAs) are widely recognized as key negative regulators in many pathophysiological processes, including inflammatory responses. Our previous transcriptome sequencing revealed numbers of differential miRNAs in BMECs upon meningitic E. coli infection; we next sought to explore whether and how these miRNAs worked to modulate neuroinflammatory responses at meningitic E. coli entry of the BBB. Here, we demonstrated in vivo and in vitro that meningitic E. coli infection of BMECs significantly downregulated miR-19b-3p, which led to attenuated production of proinflammatory cytokines and chemokines via increasing the expression of TNFAIP3, a negative regulator of NF-κB signaling. Moreover, in vivo injection of miR-19b-3p mimics during meningitic E. coli challenge further aggravated the inflammatory damage to mice brains. These in vivo and in vitro findings indicate a novel quenching mechanism of the host by attenuating miR-19b-3p/TNFAIP3/NF-κB signaling in BMECs in response to meningitic E. coli, thus preventing CNS from further neuroinflammatory damage.
Biomimetic Groundwork for Thermal Exchange Structures Inspired by Plant Leaf Design

Geometry is a determining factor for thermal performance in both biological and technical systems. While biology has inspired thermal design before, biomimetic translation of leaf morphology into structural aspects of heat exchangers remains largely unaddressed. One determinant of plant thermal endurance against environmental exposure is leaf shape, which modulates the leaf boundary layer, transpiration, evaporative cooling, and convective exchange. Here, we lay the research groundwork for the extraction of design principles from leaf shape relations to heat and mass transfer. Leaf role models were identified from an extensive literature review on environmentally sensitive morphology patterns and shape-dependent exchange. Addressing canopy sun–shade dimorphism, sun leaves collected from multiple oak species exceeded significantly in margin extension and shape dissection. Abstracted geometries (i.e., elongated; with finely toothed edges; with few large-scale teeth) were explored with paper models of the same surface area in a controlled environment of minimal airflow, which is more likely to induce leaf thermal stress. For two model characteristic dimensions, evaporation rates were significantly faster for the dissected geometries. Shape-driven transfer enhancements were higher for the smaller models, and finely toothed edges reached local cooling up to 10 °C below air temperature. This investigation breaks new ground for solution-based biomimetics to inform the design of evaporation-assisted and passively enhanced thermal systems.
Utilization of a Diet Optimization Model in Ensuring Adequate Intake among Pregnant Women in Selangor, Malaysia

Achieving nutritional requirements for pregnant women in rural or suburban households while maintaining the intake of local and culture-specific foods can be difficult. Usage of a linear programming approach can effectively generate diet optimization models that incorporate local and culturally acceptable menus. This study aimed to determine whether a realistic and affordable diet that achieves recommended nutrient intakes for pregnant women could be formulated from locally available foods in Malaysia. A cross-sectional study was conducted to assess the dietary intake of 78 pregnant women using a 24-h dietary recall and a 3-day food record. A market survey was also carried out to estimate the cost of raw foods that are frequently consumed. All linear programming analyses were done using Excel Solver to generate optimal dietary patterns. Our findings showed that the menus designed from diet optimization models using locally available foods would improve dietary adequacy for the seven food groups based on the Malaysian Dietary Guidelines 2010 (MDG 2010) and the 14 nutrients based on Recommended Nutrient Intake 2017 (RNI 2017) in pregnant women. However, inadequacies remained for iron and niacin, indicating that these nutrients may require supplementation.
Basic Human Body Dimensions Relate to Alcohol Dependence and Predict Hospital Readmission

Alcohol dependence is a severe mental illness and there is a need for more effective preventive and therapeutic strategies. Translational research suggests that intrauterine sex hormone exposure modulates the risk and course of alcohol dependence during adulthood. During development, sex hormones permanently shape sexually dimorphic body dimensions. Thus, these dimensions may provide insight into sex hormone organization. Here, we compared body measurements (absolute, relative to, and residualized on height) between 200 alcohol-dependent in-patients and 240 age-matched healthy control subjects and investigated how these measurements associate with the patients’ prospective 12- and 24-month outcome. The results show that alcohol dependence is related to lower absolute, relative, and residualized body measurements for height and weight, head circumference, bitragion head arc, lip-chin distance, hip, thigh, and calf circumference, and foot length and breadth. In male alcohol-dependent in-patients, higher risk, shorter latency, and more alcohol-related readmissions were predicted by higher absolute, relative, and residualized thigh and calf circumferences. The second-to-fourth finger length ratio, a putative proxy for prenatal sex hormone organization, was not convincingly correlated with the body dimensions, suggesting that the results represent pubertal (or later) effects. The study’s findings have implications for further research. The body measurements’ high accessibility may facilitate the future transition into clinical settings.
Blended Achievement in Transnational Schools as Collaborative Learning Communities- Toward a Systemic Assessment Framework

Education in public and private schools and higher education institutions is experiencing by beginning of the 21 st century accelerating methodical changes from massive residential to online, blended, and wireless teaching and learning. Assessment on another hand, while looked upon as the backbone of educational systems and the steering operational mechanism of classroom educational programs is either neglectfully applied or sporadically practiced as in the cases of diagnostic needs and formative assessments. Further, online schooling (OLS) is generally lacking the merits of face-to-face communication, instruction, counseling, guidance and follow-up of students' learning achievements. Hence it is urgent for OLS, to adopt a compatible systemic approach to firstly deliver curricula, instruction and learning in more rational manners; to secondly fill the assessment gap which current schooling is suffering, and thirdly to mentor students of blended learning towards their achievement ends. The systemic assessment framework presented in this article for measuring blended achievement in transnational schools as collaborative learning communities is aimed to serve above ultimate reforming purposes.
Music Perception of Cochlear Implant Users

i DECLARATION AND PREFACE . iv ACKNOWLEDGEMENTS. vi TABLE OF CONTENTS. ix TABLE OF FIGURES. xv TABLE OF TABLES. xvii LIST OF ABBREVIATIONS. xx CHAPTER 1: INTRODUCTION. 1 CHAPTER 2: OVERVIEW OF SOUND, HEARING & MUSIC . 5 2.1 SOUND.5 2.2 HEARING AND HEARING LOSS . 7 2.3 PSYCHOACOUSTICS . 10 2.3.1 Loudness.11 2.3.2 Pitch.12 2.3.3 Timbre.17 2.3. 4 The Perceptual Consequences of a Cochlear Hearing Loss.18 2.4 MUSIC . 20 2.5 MUSIC STIMULI IN COMPARISON TO SPEECH STIMULI . 21 CHAPTER 3: COCHLEAR IMPLANTS. 25 3.1 OVERVIEWOF THE COCHLEAR IMPLANT . 26 3.1.1 Nucleus Cochlear Implants.35 3.2 SPEECH PROCESSORS.37 3.2.1 Nucleus Speech Processors . 38 3.3 SPEECH-PROCESSINGSTRATEGIES.41 3.3.1 Analogue Stimulation-Based Strategies . 41 3.3.1.1 Compressed Analogue (CA) strategy . 41 3.3.1.2 Simultaneous Analogue Stimulation strategy (SAS). 42
Advancing Rheumatoid Arthritis Synovial Biopsy Analysis: One B Cell at a Time

While biologic therapies have dramatically improved the management of rheumatoid arthritis (RA), not all patients respond well to treatment and the field continues to await individualized medicine approaches that promise to determine effective medications based on a patient's distinct disease features. The cellular and molecular characterization of an individual's synovium holds promise to understand pathology, predict outcomes and tailor treatment decisions, akin to the histologic and genetic assessment of tumor tissue that guides cancer care.
Distribution of Refractive Errors among Healthy Infants and Young Children between the Age of 6 to 36 Months in Kuala Lumpur, Malaysia—A Pilot Study

Uncorrected refractive error, especially myopia, in young children can cause permanent visual impairment in later life. However, data on the normative development of refractive error in this age group is limited, especially in Malaysia. The aim of this study was to determine the distribution of refractive error in a sample of infants and young children between the ages of 6 to 36 months in a prospective, cross-sectional study. Cycloplegic retinoscopy was conducted on both eyes of 151 children of mean age 18.09 ± 7.95 months. Mean spherical equivalent refractive error for the right and left eyes was +0.85 ± 0.97D and +0.86 ± 0.98D, respectively. The highest prevalence of refractive error was astigmatism (26%), followed by hyperopia (12.7%), myopia (1.3%) and anisometropia (0.7%). There was a reduction of hyperopic refractive error with increasing age. Myopia was seen to emerge at age 24 months. In conclusion, the prevalence of astigmatism and hyperopia in infants and young children was high, but that of myopia and anisometropia was low. There was a significant reduction in hyperopic refractive error towards emmetropia with increasing age. It is recommended that vision screening be conducted early to correct significant refractive error that may cause disruption to clear vision.
Dependency on e-resources among Social Science Faculty Universities in Iran

The present study is aimed at assessment of e-resources dependency by Iranian social science faculty members. A total of 232 faculty members from various universities in Iran were randomly selected. A questionnaire for measuring dependency on various e-resources: e-books, e-journals, e-tutorials, online databases, CD-ROM databases and e-reports was a administered to sample population. Statistical methods like descriptive statistics and chi-square tests were applied to verify the hypotheses. Results showed that Iranian faculty members were more dependent on all the e-resources except for e-books selected for the study. It was also observed that Iranian faculty members were more dependent on e-journals, followed by online data bases, e-tutorials and least on e-reports. The reasons for dependency on various e-resources are discussed.
Hippocampal oscillatory dynamics and sleep atonia are altered in an animal model of fibromyalgia: Implications in the search for biomarkers

The pathogenesis of fibromyalgia is still unknown. Core symptoms include pain, depression, and sleep disturbances with high comorbidity, suggesting alterations in the monoaminergic system as a common origin of this disease. The reserpine‐induced myalgia (RIM) model lowers pain thresholds and produces depressive‐like symptoms. The present work aims to evaluate temporal dynamics in the oscillatory profiles and motor activity during sleep in this model and to evaluate if the model mimics the sleep disorders that occur in fibromyalgia patients. Hippocampal and electromyogram activity were recorded in chronically implanted rats. Following 3 days of basal recordings, reserpine was administered on three consecutive days to achieve the RIM. Postreserpine recordings were taken on alternate days for 21 days. Reserpine induced changes in the sleep architecture with more transitions between states, and a different pattern between the administration period and postreserpine weeks. Administration days were characterized by a larger amount of rapid eyes movement sleep with dominant theta waves without atonia. Following the reserpinization, theta oscillations were always more fragmented and with lower frequency. On the postreserpine days, sleep was dominated by slow‐wave sleep with fast intrusions and reduced hierarchical coupling with spindles and ripples. Simultaneous electromyography recordings also showed muscle twitches during sleep and the dissociation of theta activity and muscle atonia. Abnormally high slow waves, alpha/delta intrusions, frequent transitions, and muscle twitches are common traits in fibromyalgia. Therefore, our analyses support the validity of the RIM model to study sleep disorders in fibromyalgia, and provide new insights into the research of oscillographic biomarkers.
Single-cell gene expression analyses reveal distinct self-renewing and proliferating subsets in the leukemia stem cell compartment in acute myeloid leukemia.

Standard chemotherapy for acute myeloid leukemia (AML) targets proliferative cells and efficiently induces complete remission; however, many patients relapse and die of their disease. Relapse is caused by leukemia stem cells (LSCs), the cells with self-renewal capacity. Self-renewal and proliferation are separate functions in normal hematopoietic stem cells (HSCs) in steady state conditions. If these functions are also separate functions in LSCs, then antiproliferative therapies may fail to target self-renewal, allowing for relapse. We investigated whether proliferation and self-renewal are separate functions in LSCs as they often are in HSCs. Distinct transcriptional profiles within LSCs of Mll-AF9/NRASG12V murine AML were identified using single-cell RNA sequencing. Single-cell qPCR revealed that these genes were also differentially expressed in primary human LSCs and normal human HSPCs. A smaller subset of these genes was upregulated in LSCs relative to HSPCs; this subset of genes constitutes "LSC-specific" genes in human AML. To assess the differences between these profiles, we identified cell surface markers, CD69 and CD36, whose genes were differentially expressed between these profiles. In vivo mouse reconstitution assays revealed that only CD69High LSCs were capable of self-renewal and were poorly proliferative. In contrast, CD36High LSCs were unable to transplant leukemia but were highly proliferative. These data demonstrate that the transcriptional foundations of self-renewal and proliferation are distinct in LSCs as they often are in normal stem cells and suggest that therapeutic strategies that target self-renewal, in addition to proliferation, are critical to prevent relapse and improve survival in AML.
Epstein–Barr Virus BALF0 and BALF1 Modulate Autophagy

Autophagy is an essential catabolic process that degrades cytoplasmic components within the lysosome, therefore ensuring cell survival and homeostasis. A growing number of viruses, including members of the Herpesviridae family, have been shown to manipulate autophagy to facilitate their persistence or optimize their replication. Previous works showed that the Epstein–Barr virus (EBV), a human transforming gammaherpesvirus, hijacked autophagy during the lytic phase of its cycle, possibly to favor the formation of viral particles. However, the viral proteins that are responsible for an EBV-mediated subversion of the autophagy pathways remain to be characterized. Here we provide the first evidence that the BALF0/1 open reading frame encodes for two conserved proteins of the Bcl-2 family, BALF0 and BALF1, that are expressed during the early phase of the lytic cycle and can modulate autophagy. A putative LC3-interacting region (LIR) has been identified that is required both for BALF1 colocalization with autophagosomes and for its ability to stimulate autophagy.
Wisteria floribunda agglutinin‐positive human Mac‐2‐binding protein as a predictive marker of liver fibrosis in human immunodeficiency virus/hepatitis C virus coinfected patients

In human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfected patients, the progression of liver failure is reported to be more aggressive than that in HCV mono‐infected patients. Wisteria floribunda agglutinin‐positive human Mac‐2‐binding protein (WFA+‐M2BP) is well recognized as a liver fibrosis glycobiomarker with a unique fibrosis‐related glycoalteration. We analyzed HIV/HCV coinfected patients’ M2BP levels as a possible marker for predicting liver fibrosis.
Impaired sarcoplasmic reticulum Ca2+ release is the major cause of fatigue‐induced force loss in intact single fibres from human intercostal muscle

Changes in intramuscular Ca2+ handling contribute to development of fatigue and disease‐related loss of muscle mass and function. To date, no data on human intact living muscle fibres have been described. We manually dissected intact single fibres from human intercostal muscle and simultaneously measured force and myoplasmic free [Ca2+] at physiological temperature. Based on their fatigue resistance, two distinct groups of fibres were distinguished: fatigue sensitive and fatigue resistant. Force depression in fatigue and during recovery was due to impaired sarcoplasmic reticulum Ca2+ release in both groups of fibres. Acidification did not affect force production in unfatigued fibres and did not affect fatigue development in fatigue‐resistant fibres. The current study provides novel insight into the mechanisms of fatigue in human intercostal muscle.
Changes in pharyngeal collapsibility and genioglossus reflex responses to negative pressure during the respiratory cycle in obstructive sleep apnoea

Impaired pharyngeal anatomy and increased airway collapsibility is a major cause of obstructive sleep apnoea (OSA) and a mediator of its severity. Upper airway reflexes to changes in airway pressure provide important protection against airway closure. This study shows increased pharyngeal collapsibility and attenuated genioglossus reflex responses during expiration in people with OSA.