Cura Personalis: Institutionalizing Compassion during Emergency Remote Teaching

Faced with the fears and anxieties brought on by the COVID-19 crisis, educational institutions had to devise new compassion-based teaching and learning policies and approaches that recognized and provided for the pandemic’s psychological and emotional toll. This paper describes how the Ateneo de Manila University in the Philippines enacted its core value of cura personalis, care for the entire person, in the context of emergency remote teaching. We describe the circumstances that prompted the greater emphasis on compassion and the adjustments to classroom management, course content, class interactions, and assessment. Finally we describe the tradeoffs or costs of this approach

Transactional Distances During Emergency Remote Teaching Experiences

The Transactional Distance Theory posits that successful remote learning occurs when teachers decrease psychological or transactional gaps. Narrowing the transactional distance can be achieved through a balance of appropriate course structure and dialogue, fostering healthy student autonomy in the process. This paper describes the Emergency Remote Teaching experiences of faculty and students of the Ateneo de Manila University in the Philippines. It examines these experiences in the context of the transactional distance framework. Findings show that a sudden shift to remote learning mandates greater student autonomy, which increases transactional distance. Because of this, efforts by faculty to increase student-teacher dialogue are critical in preventing this distance from widening further. Implications for teacher professional development are subsequently discussed

Development and Field Testing of a MALL for Filipino with a Reusable Framework for Mobile-Based Drills

This paper describes the development and field testing of Ibigkas! Filipino, a mobile game that exercises learners’ fluency in identifying synonyms (kasingkahulugan) and antonyms (kasalungat) in the Filipino language. Twenty-four students from Grades 4, 5, and 6 were invited to play and answer comprehension tests to determine whether the game helped them improve their understanding of the content. Self-report questionnaires assessed the extent to which they enjoyed it. Additionally, three teachers were invited to a focus group discussion (FGD) to gather their insights about the game and how they may use it in their classes. Self-report feedback from students showed the game was fun, interesting, and sufficiently challenging. A significant increase in the post-test comprehension scores of the Grade 4 participants was found. This shows the potential of the game to make learning fun while helping realize learning goals. Teachers indicated they can use the game to supplement their Filipino classes and that the students will be receptive to the idea of utilizing a game for learning

Development and Field Testing of a Narrative-Centered Digital Game for English Comprehension

This paper describes the development and field testing of Learning Likha: Rangers to the Rescue, a narrative-centered, mobile-based digital game for practicing English comprehension. Twenty-seven (27) student participants from Grades 4, 5, and 6 were invited to play the game and answer a comprehension test to determine their level of understanding of the game’s contents. Self-report questionnaires were also used to assess the extent to which they enjoyed playing the game. Three (3) teachers were likewise invited for a focus group discussion (FGD) to gather their insights about the game and how they may use it in their classes. Student’s self-reported feedback indicated they found the game fun, interesting, and sufficiently challenging. Post-test comprehension scores were generally good. Younger participants scored lower than their older peers but the differences were found to be not significant. Teachers indicated the game has the potential to be used as a supplement for their classes and that their students would enjoy playing it

For People and Planet: Teachers’ Evaluation of an Educational Mobile Game and Resource Pack

For People and Planet: An SDG Adventure refers to a freely available Android-based narrative adventure game and teacher resource pack that helps learners see the United Nations Sustainable Development Goals (SDGs) in their day-to-day lives. In this paper, we describe the results of an evaluation of both the game and the resource pack by eight (8) middle school teachers. After playing the game and reading the resource pack, teachers gave their feedback about what they liked best and least about the materials, how they could use these resources for their classes, and how these resources could be improved further. Overall, teachers’ feedback was positive. They complemented the game’s visuals and sound design and appreciated the game’s contextualization. They affirmed the relevance of the game’s contents to their lessons and the usefulness of the teacher resource pack as it provided them with notes, additional activities, and sample assessments. They gave some useful suggestions such as the need for more visual cues within the game and tutorials for the mini-games, and glossary of terms for the teacher resource pack. The game and resource pack underwent some revision following the feedback of the teachers. Performing the user test was essential to ensuring the quality of the game and the resource pack, and to increase the probability that the game will actually be used in schools

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170.

We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER(+) or ER(-)) and human ERBB2 (HER2(+) or HER2(-)) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER(-) tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.352

Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations.

The prevalence and spectrum of germline mutations in BRCA1 and BRCA2 have been reported in single populations, with the majority of reports focused on White in Europe and North America. The Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) has assembled data on 18,435 families with BRCA1 mutations and 11,351 families with BRCA2 mutations ascertained from 69 centers in 49 countries on six continents. This study comprehensively describes the characteristics of the 1,650 unique BRCA1 and 1,731 unique BRCA2 deleterious (disease-associated) mutations identified in the CIMBA database. We observed substantial variation in mutation type and frequency by geographical region and race/ethnicity. In addition to known founder mutations, mutations of relatively high frequency were identified in specific racial/ethnic or geographic groups that may reflect founder mutations and which could be used in targeted (panel) first pass genotyping for specific populations. Knowledge of the population-specific mutational spectrum in BRCA1 and BRCA2 could inform efficient strategies for genetic testing and may justify a more broad-based oncogenetic testing in some populations

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors