Miracle-dz/UniFAR-FTUs huggingface dataset:
The Living Environment and Thermal Behaviours of Older South Australians: A Multi-Focus Group Study

Ageing brings about physiological changes that affect people’s thermal sensitivity and thermoregulation. The majority of older Australians prefer to age in place and modifications to the home environment are often required to accommodate the occupants as they age and possibly become frail. However, modifications to aid thermal comfort are not always considered. Using a qualitative approach this study aims to understand the thermal qualities of the existing living environment of older South Australians, their strategies for keeping cool in hot weather and warm in cold weather and to identify existing problems related to planning and house design, and the use of heating and cooling. Data were gathered via seven focus group sessions with 49 older people living in three climate zones in South Australia. The sessions yielded four main themes, namely ‘personal factors’, ‘feeling’, ‘knowing’ and ‘doing’. These themes can be used as a basis to develop information and guidelines for older people in dealing with hot and cold weather.
Cellular Gene Expression during Hepatitis C Virus Replication as Revealed by Ribosome Profiling

Background: Hepatitis C virus (HCV) infects human liver hepatocytes, often leading to liver cirrhosis and hepatocellular carcinoma (HCC). It is believed that chronic infection alters host gene expression and favors HCC development. In particular, HCV replication in Endoplasmic Reticulum (ER) derived membranes induces chronic ER stress. How HCV replication affects host mRNA translation and transcription at a genome wide level is not yet known. Methods: We used Riboseq (Ribosome Profiling) to analyze transcriptome and translatome changes in the Huh-7.5 hepatocarcinoma cell line replicating HCV for 6 days. Results: Established viral replication does not cause global changes in host gene expression—only around 30 genes are significantly differentially expressed. Upregulated genes are related to ER stress and HCV replication, and several regulated genes are known to be involved in HCC development. Some mRNAs (PPP1R15A/GADD34, DDIT3/CHOP, and TRIB3) may be subject to upstream open reading frame (uORF) mediated translation control. Transcriptional downregulation mainly affects mitochondrial respiratory chain complex core subunit genes. Conclusion: After establishing HCV replication, the lack of global changes in cellular gene expression indicates an adaptation to chronic infection, while the downregulation of mitochondrial respiratory chain genes indicates how a virus may further contribute to cancer cell-like metabolic reprogramming (“Warburg effect”) even in the hepatocellular carcinoma cells used here.
Women Are Seen More than Heard in Online Newspapers

Feminist news media researchers have long contended that masculine news values shape journalists’ quotidian decisions about what is newsworthy. As a result, it is argued, topics and issues traditionally regarded as primarily of interest and relevance to women are routinely marginalised in the news, while men’s views and voices are given privileged space. When women do show up in the news, it is often as “eye candy,” thus reinforcing women’s value as sources of visual pleasure rather than residing in the content of their views. To date, evidence to support such claims has tended to be based on small-scale, manual analyses of news content. In this article, we report on findings from our large-scale, data-driven study of gender representation in online English language news media. We analysed both words and images so as to give a broader picture of how gender is represented in online news. The corpus of news content examined consists of 2,353,652 articles collected over a period of six months from more than 950 different news outlets. From this initial dataset, we extracted 2,171,239 references to named persons and 1,376,824 images resolving the gender of names and faces using automated computational methods. We found that males were represented more often than females in both images and text, but in proportions that changed across topics, news outlets and mode. Moreover, the proportion of females was consistently higher in images than in text, for virtually all topics and news outlets; women were more likely to be represented visually than they were mentioned as a news actor or source. Our large-scale, data-driven analysis offers important empirical evidence of macroscopic patterns in news content concerning the way men and women are represented.
18F-FDG PET/CT Is an Early Predictor of Pathologic Tumor Response and Survival After Preoperative Radiochemotherapy with Bevacizumab in High-Risk Locally Advanced Rectal Cancer

There is an unmet need for predictive biomarkers of the clinical benefit of antiangiogenic drugs. The aim of the present study was to prospectively evaluate the value of 18F-FDG PET/CT performed during and after preoperative chemoradiotherapy with bevacizumab for the prediction of complete pathologic tumor regression and survival in patients with MRI-defined high-risk locally advanced rectal cancer. Methods: Sixty-one patients treated in a nonrandomized phase II study (BRANCH) with concomitant or sequential (4 d before chemoradiotherapy) administration of bevacizumab with preoperative chemoradiotherapy were included. 18F-FDG PET/CT was performed at baseline, 11 d after the beginning of chemoradiotherapy (early), and before surgery (late). Metabolic changes were compared with pathologic complete tumor regression (TRG1) versus incomplete tumor regression (TRG2–TRG5), progression-free survival, cancer-specific survival, and overall survival. Receiver-operating-characteristic curves were calculated for those 18F-FDG PET/CT parameters that significantly correlated with TRG1. Results: Early total-lesion glycolysis and its percentage change compared with baseline (ΔTLG-early) could discriminate TRG1 from TRG2–TRG5. Only receiver-operating-characteristic analysis of ΔTLG-early showed an area under the curve greater than 0.7 (0.76), with an optimal cutoff at 59.5% (80% sensitivity, 71.4% specificity), for identifying TRG1. Late metabolic assessment could not discriminate between the 2 groups. After a median follow-up of 98 mo (range, 77–132 mo), metabolic responders (ΔTLG-early ≥ 59.5%) demonstrated a significantly higher 10-y progression-free survival (89.3% vs. 63.6%, P = 0.02) and cancer-specific survival (92.9% vs. 72.6%, P = 0.04) than incomplete metabolic responders. Conclusion: Our results suggest that early metabolic response can act as a surrogate marker of the benefit of antiangiogenic therapy. The findings provide further support for the use of early 18F-FDG PET/CT evaluation to predict pathologic response and survival in the preoperative treatment of patients with locally advanced rectal cancer. ΔTLG-early showed the best accuracy in predicting tumor regression and may be particularly useful in guiding treatment-modifying decisions during preoperative chemoradiotherapy based on expected response.
Long-Term Galsulfase Treatment Associated With Improved Survival of Patients With Mucopolysaccharidosis VI (Maroteaux-Lamy Syndrome): 15-Year Follow-Up From the Survey Study

Mucopolysaccharidosis VI (MPS VI) is a progressive lysosomal storage disorder with multiorgan and multisystemic pathology. Currently, galsulfase enzyme replacement therapy (ERT) is the only approved treatment for MPS VI. A cross-sectional survey study of 121 patients with MPS VI conducted in 2001 to 2002 and a 10-year follow-up study of the same patients (resurvey study; ClinicalTrials.gov NCT01387854) found that those receiving galsulfase at any time showed physical improvements and a lower mortality rate (16.5%) versus treatment-naive patients (50%). After ∼15 years, galsulfase-treated patients (n = 104) continue to have a survival advantage over treatment-naive patients (n = 14), as demonstrated by a 24% versus 57% mortality rate. This survival advantage is further supported by data from the commercial use of galsulfase (2005-2016), which show a 5-year mortality rate for galsulfase-treated patients of 12.5%. Together, these findings suggest that galsulfase ERT can increase life expectancies for patient.
The E3 ubiquitin ligase parkin is dispensable for metabolic homeostasis in murine pancreatic β cells and adipocytes

The E3 ubiquitin ligase parkin is a critical regulator of mitophagy and has been identified as a susceptibility gene for type 2 diabetes (T2D). However, its role in metabolically active tissues that precipitate T2D development is unknown. Specifically, pancreatic β cells and adipocytes both rely heavily on mitochondrial function in the regulation of optimal glycemic control to prevent T2D, but parkin's role in preserving quality control of β cell or adipocyte mitochondria is unclear. Although parkin has been reported previously to control mitophagy, here we show that, surprisingly, parkin is dispensable for glucose homeostasis in both β cells and adipocytes during diet-induced insulin resistance in mice. We observed that insulin secretion, β cell formation, and islet architecture were preserved in parkin-deficient β cells and islets, suggesting that parkin is not necessary for control of β cell function and islet compensation for diet-induced obesity. Although transient parkin deficiency mildly impaired mitochondrial turnover in β cell lines, parkin deletion in primary β cells yielded no deficits in mitochondrial clearance. In adipocyte-specific deletion models, lipid uptake and β-oxidation were increased in cultured cells, whereas adipose tissue morphology, glucose homeostasis, and beige-to-white adipocyte transition were unaffected in vivo. In key metabolic tissues where mitochondrial dysfunction has been implicated in T2D development, our experiments unexpectedly revealed that parkin is not an essential regulator of glucose tolerance, whole-body energy metabolism, or mitochondrial quality control. These findings highlight that parkin-independent processes maintain β cell and adipocyte mitochondrial quality control in diet-induced obesity.
Mental health screening in integrated care settings: Identifying rates of depression, anxiety, and posttraumatic stress among youth with HIV

ABSTRACT Rates of depression, anxiety, and posttraumatic stress disorder (PTSD) are greater in youth living with HIV (YLWH) than in the general population. Currently, depression screening guidelines exist for YLWH but not anxiety and PTSD. This study examined data from comprehensive mental health screenings conducted with YLWH, which included measures of depression, anxiety, and PTSD. Percentages of positive screeners were 35%, 25.7%, and 20.6% for depression, anxiety, and PTSD, respectively. Older participants reported more depression and anxiety symptoms. Participants with less education reported more PTSD symptoms. These findings support the need for universal and comprehensive mental health screenings for YLWH.
Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) and Endolysosomal Two-pore Channels Modulate Membrane Excitability and Stimulus-Secretion Coupling in Mouse Pancreatic β Cells*

Background: TPCs are regulated by NAADP and other factors. Results: NAADP-induced Ca2+ release from acidic stores evokes depolarizing currents in pancreatic β cells. Inhibition of NAADP signaling or TPC knock out attenuates Ca2+ signaling and insulin secretion. Conclusion: NAADP-evoked Ca2+ release enhances β cell excitability and insulin secretion in response to glucose or sulfonylureas. Significance: NAADP signaling pathways offer novel therapeutic targets for diabetes treatment. Pancreatic β cells are electrically excitable and respond to elevated glucose concentrations with bursts of Ca2+ action potentials due to the activation of voltage-dependent Ca2+ channels (VDCCs), which leads to the exocytosis of insulin granules. We have examined the possible role of nicotinic acid adenine dinucleotide phosphate (NAADP)-mediated Ca2+ release from intracellular stores during stimulus-secretion coupling in primary mouse pancreatic β cells. NAADP-regulated Ca2+ release channels, likely two-pore channels (TPCs), have recently been shown to be a major mechanism for mobilizing Ca2+ from the endolysosomal system, resulting in localized Ca2+ signals. We show here that NAADP-mediated Ca2+ release from endolysosomal Ca2+ stores activates inward membrane currents and depolarizes the β cell to the threshold for VDCC activation and thereby contributes to glucose-evoked depolarization of the membrane potential during stimulus-response coupling. Selective pharmacological inhibition of NAADP-evoked Ca2+ release or genetic ablation of endolysosomal TPC1 or TPC2 channels attenuates glucose- and sulfonylurea-induced membrane currents, depolarization, cytoplasmic Ca2+ signals, and insulin secretion. Our findings implicate NAADP-evoked Ca2+ release from acidic Ca2+ storage organelles in stimulus-secretion coupling in β cells.
Application of Isometric Resistance Training to Treat Hypertension

iv Acknowledgements . v List of Tables . viii List of Figures . ix List of Appendices . x List of Abbreviations . xi Chapter 1: Literature Review . 1 1.1 Cardiovascular Disease . 2 1.2 Hypertension . 3 1.2. 3 Blood Pressure Regulation . 5 1.2. 4 Blood Pressure Measurement . 10 1.2. 5 Pathophysiology of Hypertension . 14 1.2. 6 Prevention/Treatment of Hypertension . 16 1.3 Exercise Training . 19 1.3. 1 Acute Effects of Exercise on Blood Pressure . 20 1.3. 2 Chronic Effects of Exercise on Blood Pressure . 24 1.4 Cardiovascular Reactivity . 33 1.5 Detraining Effects on Blood Pressure . 34 1.6 Summary . 37 1.7 References . 39
Short Term Quality of Life After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

Peritoneal carcinomatosis (PC), which is called the advanced stage of abdominal cancer, continues to be a concern that has not been completely resolved in the present time. Due to both medical cost burdens and inferior treatment results of oncologic diseases with palliative chemo-radiotherapy or supportive care in advance, in 1989 Sugarbaker et al. (1) presented cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) as a remarkable method for appropriate patients with PC. Initially, this technique had excessive treatment-related morbidity and mortality as a major concern. However, completion of the learning curve in the experienced centers resulted an overall decrease in the postoperative morbidity and mortality, as shown in the recent studies (2, 3).
Expression of CD45, CD34, CD10, and human leukocyte antigen-DR in acute lymphoblastic leukemia

Background: Immunophenotypic analysis of leukemic cells by multicolor flow cytometry using different monoclonal antibodies labeled to various flourochromes, is an important, precise and rapid investigation for diagnosis, classification, prognosis prediction, and minimal residual disease detection in acute lymphoblastic leukemia (ALL). Objectives: The aims of study were to study the expression of CD45, CD34, CD10, human leukocyte antigen-DR (HLA-DR) in B and T-ALL among 114 Iraqi patients and compare findings with other reports worldwide. Patients, Materials and Methods: A retrospective cross-sectional study was conducted on 114 ALL patients of various age groups from different hematology centers in Baghdad who were referred to Flowcytometry Department at the Bone Marrow Transplantation Center/Private Nursing Home Hospital/Medical City for immunophenotypic classification using multi-color flow cytometry from the January 1, 2016, to the August 31, 2016. Results: Out of 114 patients, 71 patients were pediatric patients and 43 were adults. Eighty-three patients were classified as B-cell ALL and 31 patients as T-cell ALL. There was significant association between male gender, high white blood cells count and T-cell ALL subtype. Negative-dim-moderate CD45, positive CD34, and positive HLA-DR expressions were significantly associated with B-cell ALL. Common ALL antigen was seen in 86.7% of the B-cell ALL patients and was accompanied cTdT expression. Aberrant myeloid antigens were observed in 22.9% of B-cell ALL patients and in 35.5% of T-cell ALL. About 4.8% of the patients with B-cell ALL had aberrant T-linage antigens while 6.5% of the patients with T-cell ALL expressed aberrant B-cell lineage antigens. Conclusion: Immunophenotypic expression of ALL cells among Iraqi patients is to somewhat in accordance with various researches worldwide making immunophenotyping flow cytometry a crucial appliance in diagnosis, classification, risk stratification, and minimal residual disease detection in ALL.
Clinical study of co-relation between positive axillary lymph node status and size of the tumor in breast malignancies

Background: Breast lump in women is a common clinical condition encountered in day-to-day surgical practice and needs thorough evaluation. This study is focused on co-relation between axillary lymph nodal status and the size of the breast tumor through clinical, radioimaging, and pathological studies. The axillary lymph node study also helps to differentiate benign from malignant breast lumps. Patients and Methods: This study was carried out in the Department of Surgery, Great Eastern Medical School (GEMS) Hospital, Ragolu, Srikakulam, Andhra Pradesh, India. A total of 45 patients were selected for the study from among admitted cases to the Department of Surgery through clinical assessment, laboratory investigations, and ultrasound findings. After confirming the diagnosis of breast malignancy by fine needle aspiration cytology and Trucut biopsy in few cases, the patient had undergone operative intervention. Later, the specimens were sent for histopathological study. Results: Breast malignancy was found more commonly among female patients of 45–64 years of age with an incidence of 66% in present studies. Lump in the breast was the common presenting feature in all patients. Ultrasound findings and Trucut biopsy have shown high sensitivity and specificity up to 97–99%. Conclusion: The present study concludes that for the tumor size <10 mm, axillary lymph node dissection may not be needed. Larger the size of the tumor, the more probability of lymph nodal metastasis.
Delayed γH2AX foci disappearance in mammary epithelial cells from aged women reveals an age-associated DNA repair defect

Aging is a degenerative process in which genome instability plays a crucial role. To gain insight into the link between organismal aging and DNA repair capacity, we analyzed DNA double-strand break (DSB) resolution efficiency in human mammary epithelial cells from 12 healthy donors of young and old ages. The frequency of DSBs was measured by quantifying the number of γH2AX foci before and after 1Gy of γ-rays and it was higher in cells from aged donors (ADs) at all times analyzed. At 24 hours after irradiation, ADs retained a significantly higher frequency of residual DSBs than young donors (YDs), which had already reached values close to basal levels. The kinetics of DSB induction and disappearance showed that cells from ADs and YDs repair DSBs with similar speed, although analysis of early times after irradiation indicate that a repair defect may lie within the firing of the DNA repair machinery in AD cells. Indeed, using a mathematical model we calculated a constant factor of delay affecting aged human epithelial cells repair kinetics. This defect manifests with the accumulation of DSBs that might eventually undergo illegitimate repair, thus posing a relevant threat to the maintenance of genome integrity in older individuals.
Chronic myeloid leukemia and ferritin levels

Background: Ferritin is a positive acute-phase reactant, exhibiting increased levels in blood during the acute-phase response. High plasma ferritin levels have been reported for various types of cancers, irrespective of the amount of total body iron. Hence, this study was designed to assess the status of ferritin levels in chronic myeloid leukemia (CML) patients both before and after chemotherapy and to compare them with age- and sex-matched healthy controls. Methods: Thirty patients of CML after confirmed diagnosis were taken up for the study. CML patients were treated by imatinib therapy. Serum ferritin was estimated by enzyme-linked immunosorbent assay in thirty newly diagnosed CML patients and in thirty age- and sex-matched healthy controls. The test was repeated at first complete remission or at 3 months (whichever is earlier) in CML patients. Patients and controls were categorized into three groups as follows: (1) Group I: Control group –age- and sex-matched healthy volunteers (2) Group II: CML patients at the time of diagnosis (before imatinib therapy) (3) Group III: CML patients at first complete remission or at 3 months of imatinib therapy (whichever is earlier). Results: The ferritin levels were significantly increased in Group II and Group III (387.68 ± 221.61 ng/mL and 295.43 ± 169.17 ng/mL, respectively) as compared to controls (73.27 ± 60.82 ng/mL) (P = 0.000 and P = 0.000, respectively). The ferritin levels were decreased in Group III as compared to Group II, although the difference was not statistically significant (P = 0.075). Conclusion: Our study revealed that serum ferritin could be a useful marker in determining disease progression or monitor the effectiveness of treatment in leukemic patients.
Hearing impairment in children with congenital cytomegalovirus (CMV) infection based on distortion product otoacoustic emissions (DPOAE) and brain evoked response audiometry stimulus click (BERA Click) examinations

Congenital cytomegalovirus (congenital CMV) infection is a leading factor of nongenetic sensorineural hearing loss in children. Hearing loss caused by CMV infection does not have a pathognomonic configuration hence further research is needed. The development of knowledge on hearing loss caused by congenital CMV infection is progressing in many countries. Due to a lack of research in the context of Indonesia, this study assesses hearing impairment in children with congenital CMV infection in Indonesia, more specifically in the Cipto Mangunkusumo Hospital. Our objective was to profile hearing impairment in children 0-5 years of age with congenital CMV infection using Distortion Product Otoacoustic Emissions (DPOAE) and Brain Evoked Response Audiometry Stimulus Click (BERA Click) examinations. This cross-sectional study was conducted in the Cipto Mangunkusum Hospital from November, 2015 to May 2016 with 27 children 0-5 years of age with congenital CMV infection. Of individual ears studied, 58.0% exhibited sensorineural hearing loss. There was a significant relationship between developmental delay and incidence of sensorineural hearing loss. Subjects with a developmental delay were 6.57 times more likely (CI 95%; 1.88-22.87) to experience sensorineural hearing loss. Congenital CMV infection has an important role in causing sensorineural hearing loss in children.