Chemoresistance in human ovarian cancer: the role of apoptotic regulators

Ovarian cancer is among the most lethal of all malignancies in women. While chemotherapy is the preferred treatment modality, chemoresistance severely limits treatment success. Recent evidence suggests that deregulation of key pro- and anti-apoptotic pathways is a key factor in the onset and maintenance of chemoresistance. Furthermore, the discovery of novel interactions between these pathways suggests that chemoresistance may be multi-factorial. Ultimately, the decision of the cancer cell to live or die in response to a chemotherapeutic agent is a consequence of the overall apoptotic capacity of that cell. In this review, we discuss the biochemical pathways believed to promote cell survival and how they modulate chemosensitivity. We then conclude with some new research directions by which the fundamental mechanisms of chemoresistance can be elucidated

Use of clinical chromosomal microarray in Chinese patients with autism spectrum disorder—implications of a copy number variation involving DPP10

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Copy number variation in Hong Kong patients with autism spectrum disorder

Oral Free Paper Session: Oral Presentation 6 [best oral presentation]BACKGROUND AND AIMS: When offering chromosomal microarray for patients with autism spectrum disorder (ASD), as according to international standards, copy number variations of uncertain significance (CNV VUS) are frequently identified, which leads to challenges in genetic counselling. We aim to study the CNV findings in children with ASD in Hong Kong, and to gather information for reclassification of recurrent CNV VUS. METHODS: ASD patients from the Department of Paediatrics and Adolescent Medicine QMH/HKU were recruited if their Array Comparative Genomic Hybridization (aCGH) were done anytime from January 2011 to August 2014 in Prenatal Diagnostic Laboratory, Tsan Yuk Hospital. Diagnosis of ASD was made by developmental paediatricians and clinical psychologists using the criteria from Diagnostic and Statistical Manual of Mental Disorders, Fourth or Fifth Edition. NimbleGen CGX-135k oligonucleotide array and Agilent CGX 60k oligonucleotide array were used. Information was summarised from the literature and existing databases to re-classify CNV VUS occurring in our ASD cohort. RESULTS: Among 288 patients with ASD in our cohort, we identified 5 patients with pathogenic CNV (1.74%) and 5 patients with likely pathogenic CNV (1.74%). Among all the CNV VUS, one variant overlapping DPP10 (hg[19] chr2:116,534,689-116,672,358) was recurrently found in Chinese individuals. The frequency of this variant in our ASD cohort was 0.35% (1 in 288), and 0.96% (9 in 935) in our controls. (P=0.467, two-tailed Fisher’s exact test). Similar CNVs were suggested to be ASD-related in previous studies recruiting mainly Caucasians. However, there were Chinese individuals with typical development possessing similar CNVs identified in independent sources (9 from our internal database, 1 from Singapore Genome Variation Project, 24 from The Singapore Prospective Study Program). CONCLUSIONS: Our study explored the CNV findings in Hong Kong paediatric ASD patients. The CNV overlapping DPP10 may be a Chinese-related copy-number variation in Hong Kong Chinese, and we reclassified it to be likely benign in our locality. Our result emphasized the need to account for ethnicity to give the most precise interpretation of aCGH data.published_or_final_versio

Classification and Lateralization of Temporal Lobe Epilepsies with and without Hippocampal Atrophy Based on Whole-Brain Automatic MRI Segmentation

Brain images contain information suitable for automatically sorting subjects into categories such as healthy controls and patients. We sought to identify morphometric criteria for distinguishing controls (n = 28) from patients with unilateral temporal lobe epilepsy (TLE), 60 with and 20 without hippocampal atrophy (TLE-HA and TLE-N, respectively), and for determining the presumed side of seizure onset. The framework employs multi-atlas segmentation to estimate the volumes of 83 brain structures. A kernel-based separability criterion was then used to identify structures whose volumes discriminate between the groups. Next, we applied support vector machines (SVM) to the selected set for classification on the basis of volumes. We also computed pairwise similarities between all subjects and used spectral analysis to convert these into per-subject features. SVM was again applied to these feature data. After training on a subgroup, all TLE-HA patients were correctly distinguished from controls, achieving an accuracy of 96 ± 2% in both classification schemes. For TLE-N patients, the accuracy was 86 ± 2% based on structural volumes and 91 ± 3% using spectral analysis. Structures discriminating between patients and controls were mainly localized ipsilaterally to the presumed seizure focus. For the TLE-HA group, they were mainly in the temporal lobe; for the TLE-N group they included orbitofrontal regions, as well as the ipsilateral substantia nigra. Correct lateralization of the presumed seizure onset zone was achieved using hippocampi and parahippocampal gyri in all TLE-HA patients using either classification scheme; in the TLE-N patients, lateralization was accurate based on structural volumes in 86 ± 4%, and in 94 ± 4% with the spectral analysis approach. Unilateral TLE has imaging features that can be identified automatically, even when they are invisible to human experts. Such morphometric image features may serve as classification and lateralization criteria. The technique also detects unsuspected distinguishing features like the substantia nigra, warranting further study

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

A new approach to understand female breast cancer experiences: a study of a movement based focus group of women with breast cancer

Conference Theme: New Horizons in Cancer Car

Scales of spatiotemporal variability in macroinvertebrate abundance and diversity in monsoonal streams: Detecting environmental change

1.We quantified spatial and temporal variability in benthic macroinvertebrate species richness, diversity and abundance in six unpolluted streams in monsoonal Hong Kong at different scales using a nested sampling design. The spatial scales were regions, stream sites and stream sections within sites; temporal scales were years (1997-99), seasons (dry versus wet seasons) and days within seasons. 2.Spatiotemporal variability in total abundance and species richness was greater during the wet season, especially at small scales, and tended to obscure site- and region-scale differences, which were more conspicuous during the dry season. Total abundance and richness were greater in the dry season, reflecting the effects of spate-induced disturbance during the wet season. Species diversity showed little variation at the seasonal scale, but variability at the site scale was apparent during both seasons. 3.Despite marked variations in monsoonal rainfall, inter-year differences in macroinvertebrate richness and abundance at the site scale during the wet season were minor. Inter-year differences were only evident during the dry season when streams were at base flow and biotic interactions may structure assemblages. 4.Small-scale patchiness within riffles was the dominant spatial scale of variation in macroinvertebrate richness, total abundance and densities of common species, although site or region was important for some species. The proportion of total variance contributed by small-scale spatial variability increased during the dry season, whereas temporal variability associated with days was greater during the wet season. 5.The observed patterns of spatiotemporal variation have implications for detection of environmental change or biomonitoring using macroinvertebrate indicators in streams in monsoonal regions. Sampling should be confined to the dry season or, in cases where more resources are available, make use of data from both dry and wet seasons. Sampling in more than one dry season is required to avoid the potentially confounding effects of inter-year variation, although variability at that scale was relatively small. © 2011 Blackwell Publishing Ltd.link_to_subscribed_fulltex

The use of NOS understandings in the evaluation of Science News by Nonscience Majors

Conference Theme: Toward Equity and Justice: Many Different Voices, Cultures, and Languages in Science Education Research for Quality Science Learning and TeachingCritical evaluation of reports about science news has been a desired outcome from a scientifically literate populace. Without science background as sophisticated as scientists’, evaluation of science news proves a challenge to the public. It is generally assumed that understandings of nature of science (NOS) will lead to this desired outcome of scientific literacy. This paper aimed at examining the criteria applied and the capacity in which they were applied by nonscience majors in evaluating science news. Sixty-four nonscience majors from a local community college completed the Health News Evaluation Questionnaire. Participants focused more on the cognitive aspects of science than the social or epistemological aspect in the evaluation, and news of socioscientific nature elicited more responses pertaining to the social aspect of science than reports of scientific research. These indicated the capacity of nonscience majors in drawing upon the cognitive aspects of science despite their limited science background. This study demonstrated the use of NOS aspects and the degree and capacity to which they were applied in the evaluation of science in the media by nonscience majors, and laid the foundation for future studies to further explore the assumed role of NOS in critical evaluation of science news

Understandings of Nature of Science and Multiple Perspective Evaluation of Science News by Non-science Majors

Understandings of nature of science (NOS) are a core component of scientific literacy, and a scientifically literate populace is expected to be able to critically evaluate science in the media. While evidence has remained inconclusive on whether better NOS understandings will lead to critical evaluation of science in the media, this study aimed at examining the correlation therein. Thirty-eight non-science majors, enrolled in a science course for non-specialists held in a local community college, evaluated three health news articles by rating the extent to which they agreed with the reported claims and providing as many justifications as possible. The majority of the participants were able to evaluate and justify their viewpoint from multiple perspectives. Students’ evaluation was compared with their NOS conceptions, including the social and cultural embedded NOS, the tentative NOS, the peer review process and the community of practice. Results indicated that participants’ understanding of the tentative NOS was significantly correlated with multiple perspective evaluation of science news reports of socioscientific nature (r = 0.434, p < 0.05). This moderate correlation suggested the association between understanding of the tentative NOS and multiple perspective evaluation of science in the media of socioscientific nature. However, the null result for other target NOS aspects in this study suggested a lack of evidence to assume that understanding the social dimensions of science would have significant influence on the evaluation of science in the media. Future research on identifying the reasons for why and why not NOS understandings are applied in the evaluation will move this field forward