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Previous studies have shown that inquiry-based learning (IBL) and flipped learning effectively promote student engagement and learning outcomes in language classrooms. Meanwhile, technology-enhanced formative assessment (TEFA) with well-designed instructional strategies can provide engaging learning opportunities for learners of English as a Foreign Language (EFL). However, research on combining these three teaching approaches to enhance foreign language skills is scarce. Specifically, this study integrated IBL and TEFA in flipped EFL writing instruction to address the research gap. A mixed-method design was employed to explore 48 students' writing performance and their perceptions of these creative teaching strategies. The results of the quantitative analysis indicate that combining IBL and TEFA increased students' writing quality, as shown by the significant difference between their pretest and posttest writing scores. In addition, qualitative analysis of their written reflections indicated that they appreciated the dynamic and interactive learning atmosphere, displayed positive attitudes, and perceived the value of IBL and TEFA. The students also provided insights regarding the difficulties they experienced with this teaching method. The implications concerning the impact of IBL and TEFA in teaching flipped EFL writing are discussed, highlighting future suggestions for EFL educators.

The anion exchanger protein SLC26A3 (down-regulated in adenoma, DRA) is expressed in the luminal membrane of intestinal epithelial cells in colon, where it facilitates the absorption of Cl- and oxalate. We previously identified a 4,8-dimethylcoumarin class of SLC26A3 inhibitors that act from the SLC26A3 cytoplasmic surface, and demonstrated their efficacy in mouse models of constipation and hyperoxaluria. Here, screening of 50,000 new compounds and 1740 chemical analogs of active compounds from the primary screen produced five novel classes of SLC26A3-selective inhibitors (1,3-dioxoisoindoline-amides; N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)acetamides; thiazolo-pyrimidin-5-ones; 3-carboxy-2-phenylbenzofurans and benzoxazin-4-ones) with IC50 down to 100 nM. Kinetic washout and onset of action studies revealed an extracellular site of action for the thiazolo-pyrimidin-5-one and 3-carboxy-2-phenylbenzofuran inhibitors. Molecular docking computations revealed putative binding sites for these inhibitors. In a loperamide model of constipation in mice, orally administered 7-(2-chloro-phenoxymethyl)-3-phenyl-thiazolo [3,2-a]pyrimidin-5-one (3a) significantly increased stool weight, pellet number and water content. SLC26A3 inhibitors with an extracellular site of action offer the possibility of creating non-absorbable, luminally acting inhibitors with minimal systemic exposure following oral administration. Our findings also suggest that inhibitors of related SLC26 anion transporters with an extracellular site of action might be identified for pharmacological modulation of selected epithelial ion transport processes.

Previous studies have shown that inquiry-based learning (IBL) and flipped learning effectively promote student engagement and learning outcomes in language classrooms. Meanwhile, technology-enhanced formative assessment (TEFA) with well-designed instructional strategies can provide engaging learning opportunities for learners of English as a Foreign Language (EFL). However, research on combining these three teaching approaches to enhance foreign language skills is scarce. Specifically, this study integrated IBL and TEFA in flipped EFL writing instruction to address the research gap. A mixed-method design was employed to explore 48 students’ writing performance and their perceptions of these creative teaching strategies. The results of the quantitative analysis indicate that combining IBL and TEFA increased students’ writing quality, as shown by the significant difference between their pretest and posttest writing scores. In addition, qualitative analysis of their written reflections indicated that they appreciated the dynamic and interactive learning atmosphere, displayed positive attitudes, and perceived the value of IBL and TEFA. The students also provided insights regarding the difficulties they experienced with this teaching method. The implications concerning the impact of IBL and TEFA in teaching flipped EFL writing are discussed, highlighting future suggestions for EFL educators.

This paper explores the ways in which Mexican immigrants experience, narrate, and describe stress and the extent to which it impacts their efforts at engaging in physical activity using a biocitizenship framework. Data were derived from a mixed-method study among Mexicans living in New York City recruited from a large Catholic church. The qualitative sample of 25 participated in quantitative and qualitative components of the study and as such we include some of these quantitative indicators as descriptors. Our main qualitative findings reveal that study participants experience stress and time constraint as factors that contribute to the waning of their physical and mental well-being. As such, time constraints for many of our participants were among the factors that contributed to high perceived levels of stress. They attributed this to their difficulty maintaining a physically active lifestyle due to factors like the fast-paced lifestyle in New York, working long hours, and not having enough time to exercise, though some important differences in narratives were noted across gender. Findings have implications for interventions aimed at improving the health of immigrants in general and Mexican immigrants in New York City specifically.

Colleges are engaging students in collaborative design courses on diverse projects. More of the courses could be focusing on cross-disciplinary entrepreneurship projects including computer science and information systems students with other disciplinary students. The authors of this paper describe a course that is focusing on collaborative design and cross-disciplinary entrepreneurship on innovation projects by students as members of self-directed teams. The course is involving the students on crowdfunding projects of product prototyping, from which they are learning a marketable repertoire of skills. The findings of this paper will be beneficial to educators in colleges of computer science and information systems considering enriching pedagogical practices to be contemporary with the demands of industry.

The present study examined the perception of teachers of the new educational curriculum in Ghana. Responses from six teachers interviewed were developed into a questionnaire and posted on the websites of teacher unions via WhatsApp. In all, 74 teachers responded. From the study teachers perceived that the new curriculum is important as it will encourage group work, assist students to get lifelong skills, prepare students for the job market, promote inclusive education, promote gender equality, and considers Ghanaian students' culture and society. The findings further revealed that the current curriculum does not includes difficult content for teaching but contains a lot of workloads, lacks teaching and learning materials and includes long class periods. Teachers were also of the view that the government should involve teachers in planning the curriculum, get books and learning materials ready, train teachers in advance and pilot a new curriculum before implementation. In a nutshell, the new curriculum should involve many teachers in planning before implementation.

College students can be advocates for people with disabilities. Collaboration on community projects in a school of computer science and information systems can be desirable for people with disabilities and students. The authors analyze the collaborative impacts from courses in Web Design for Non-Profit Organizations with moderately impaired but nimble people with cognitive disabilities. The authors find course features of e-Portfolios facilitating the engagement and the advocacy of the students for mentored people with disabilities. The findings can help instructors in information systems in cultivating e-Portfolios on course projects of students with those with disabilities.

Objective: To determine the risk of malignancy of Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) indeterminate Thyroid Nodules (Bethesda III, IV and V) by combining cytologic (TSBRTC) and Thyroid Imaging Reporting and Data Systems (TI-RADS) ultrasonographic features based on final histopathology. Methods: Design: Retrospective review of records Setting: Tertiary Private Training Hospital Participants: 551 records Results: Among 81 eligible participants, 59 out of 84 nodules (70.24%) wer malignant on histopathology. The malignancy risk of Bethesda classification was 60.87% (28 out of 46) for Bethesda III, 57.14% (8 out of 14) for Bethesda IV and 95.83% for Bethesda V. The malignancy risk for TI-RADS categories was 0 % (0/1) for TI-RADS 2, 50% (10 out of 20) for TI-RADS 3, 71.05 % for TI-RADS 4 and 91.67 % for TI-RADS 5. The highest risk of malignancy (100%) was associated with [Bethesda IV/TI-RADS 1, 2, and 3], [Bethesda V/TI-RADS 1, 2 and 3 [Bethesda IV and V/TI-RADS 1, 2 and 3] and [Bethesda IV/TI-RADS 5]. The lowest risk of malignancy (33.33%) was associated with [Bethesda III/TI-RADS1, 2 and 3]. A high Bethesda classification (Bethesda V) was almost 5x more likely to have a malignant anatomorphology compared with Bethesda III (p = .05) while a TI-RADS 4 or 5 category was almost 5x more likely to have a malignant anatomorphology compared to TI-RADS 1, 2 or 3 (p = .026). Conclusion: This study showed that TI-RADS scoring is a sensitive diagnostic classification in recognizing patients with thyroid cancer and combining Bethesda classification and TI-RADS scoring increases the sensitivity in the diagnosis of malignant thyroid nodules. A higher likelihood of malignancy is associated with higher Bethesda classification and TI-RADS scoring.

SLC26A6 (also known as putative anion transporter 1 [PAT1]) is a Cl-/HCO3- exchanger expressed at the luminal membrane of enterocytes where it facilitates intestinal Cl- and fluid absorption. Here, high-throughput screening of 50,000 synthetic small molecules in cells expressing PAT1 and a halide-sensing fluorescent protein identified several classes of inhibitors. The most potent compound, the pyrazolo-pyrido-pyrimidinone PAT1inh-B01, fully inhibited PAT1-mediated anion exchange (IC50 ~350 nM), without inhibition of the related intestinal transporter SLC26A3 (also known as DRA). In closed midjejunal loops in mice, PAT1inh-B01 inhibited fluid absorption by 50%, which increased to >90% when coadministered with DRA inhibitor DRAinh-A270. In ileal loops, PAT1inh-B01 blocked fluid absorption by >80%, whereas DRAinh-A270 was without effect. In colonic loops, PAT1inh-B01 was without effect, whereas DRAinh-A270 completely blocked fluid absorption. In a loperamide constipation model, coadministration of PAT1inh-B01 with DRAinh-A270 increased stool output compared with DRAinh-A270 alone. These results provide functional evidence for complementary and region-specific roles of PAT1 and DRA in intestinal fluid absorption, with PAT1 as the predominant anion exchanger in mouse ileum. We believe that PAT1inh-B01 is a novel tool to study intestinal ion and fluid transport and perhaps a drug candidate for small intestinal hyposecretory disorders such as cystic fibrosis-related meconium ileus and distal intestinal obstruction syndrome.

Policy-makers in Ireland advocate teacher collaboration as being a vital component of educational reform and school improvement in inclusive and participatory communities of practice. The objective of this research study was to attempt to achieve a depth of understanding of the role played by principals in the reification of the Department of Education and Skills (DES) policy around collaborative practice in their schools. This paper attempts to capture a snapshot of the current culture around teacher collaborative practice and the extent to which such practice is enabled and/or encouraged by senior management. A qualitative approach was used to gather the necessary data which were analysed using a grounded theory approach. Some key findings include: principals have an astute awareness of how collaborative practice is conceptualised and contextualised within the Irish education system; there exists a broad range of formal and informal practices already at play; principals believe that clear structures and strategies will herald the creation of a new pedagogical landscape propagated by meaningful and highly effective collaborative practice; school leaders actively encourage and endorse collaborative practice; principals are positively seeking to re-culture schools and mediate the traditional norms that many teachers are essentially fearful to forsake.

The demand for graduates in STEM continues to expand in industry. To address the demand, not enough focus is on programs for students with disabilities having knowledge in STEM. This paper describes a post-secondary program at a school of computer science and information systems that is contributing marketability in STEM for moderately impaired but intellectually nimble students with developmental and intellectual disabilities. The findings of this paper denote contributions of academic identity, content learning of information systems technology and limited norms of sociability from the program, as a foundation for opportunities in STEM for the students. The results of this study can encourage other schools of computer science and information systems in pursuing special education programs in STEM for this niche population of students.

College does not bestow enough engagement of computer science and information systems students with higher-functioning people with disabilities. Information systems students without disabilities do not have enough experiences in diversity with equivalently skilled students with disabilities. In this paper, the authors expand the knowledge of information systems students without disabilities through "Disability Film Festivals" depicting not the impairments but the intelligence of those with disabilities. The authors learn that features of the films are facilitating engagement and facilitating advocacy of the information systems students for the diversity of those with disabilities having inherent information systems skills. The findings of this study from 2015 will be beneficial to information systems professors and students in encouraging more receptivity to higher-functioning students with disabilities.

BackgroundPancreatic ductal adenocarcinoma (PDAC) is the most common pancreatic malignancy, which rarely metastasizes to the spine.Case descriptionHere, we present a lytic lumbar metastatic PDAC resulting in severe epidural spinal cord compression (ESCC) with instability. The lesion required preoperative particle embolization, surgical decompression, and fusion.ConclusionThis case report shows that PDAC may metastasize to the lumbar spine requiring routine decompression with fusion.

Available CFTR modulators provide no therapeutic benefit for cystic fibrosis (CF) caused by many loss-of-function mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel, including N1303K. We previously introduced the concept of 'co-potentiators' (combination-potentiators) to rescue CFTR function in some minimal function CFTR mutants. Herein, a screen of ~120,000 drug-like synthetic small molecules identified active co-potentiators of pyrazoloquinoline, piperidine-pyridoindole, tetrahydroquinoline and phenylazepine classes, with EC50 down to ~300 nM following initial structure-activity studies. Increased CFTR chloride conductance by up to 8-fold was observed when a co-potentiator (termed 'Class II potentiator') was used with a classical potentiator ('Class I potentiator') such as VX-770 or GLPG1837. To investigate the range of CFTR mutations benefitted by co-potentiators, 14 CF-associated CFTR mutations were studied in transfected cell models. Co-potentiator efficacy was found for CFTR missense, deletion and nonsense mutations in nucleotide binding domain-2 (NBD2), including W1282X, N1303K, c.3700A > G and Q1313X (with corrector for some mutations). In contrast, CFTR mutations G85E, R334W, R347P, V520F, R560T, A561E, M1101K and R1162X showed no co-potentiator activity, even with corrector. Co-potentiator efficacy was confirmed in primary human bronchial epithelial cell cultures generated from a N1303K homozygous CF subject. The Class II potentiators identified here may have clinical benefit for CF caused by mutations in the NBD2 domain of CFTR.

Abstract Background There is growing attention and policy debate about the sharing of personal information that the modernization of electricity grids requires. This is particularly important for big data management in smart grids that needs access to data generated and sent through devices such as smart meters. Using the Nordic Countries as a case study, this study investigates the willingness of people to share personal information for energy efficiency. The study builds upon data from the Eurobarometer survey and binary logistic regressions. Results Nordic countries exhibit a higher willingness to share personal information compared to the rest of the EU countries. However, despite high levels of concern for climate change and other pro-environmental attitudes found overall among Europeans, the willingness to share personal information is not as prevalent and is still mainly shaped by socio-demographic features such as gender and age. Key predictors also included climate change perception and congruence of citizen engagement with environmentally friendly behaviors. Several contextual and market-specific issues framing these findings are discussed (e.g., trust, energy use). Conclusions Even when high levels of pro-environmental attitudes in certain countries are found, let alone the Nordics, this does not mean people are willing to share personal information that would support pro-environmental energy efficiency behaviors and policies.

Super-resolution microscopy in cultured cells is employed to dissect the effect of hydroxychloroquine (HCQ) at the plasma membrane and HCQ directly perturbs clustering of the SARS-CoV-2 receptor ACE2 with endocytic lipids and PIP2 clusters.

Firms in industry continue to be attracted by the benefits of Big Data Analytics. The benefits of Big Data Analytics projects may not be as evident as frequently indicated in the literature. The authors of the study evaluate factors in a customized methodology that may increase the benefits of Big Data Analytics projects. Evaluating firms in the financial industry, the authors find that business and procedural factors, such as collaboration maturity of the organization and Big Data Analytics governance, are more important than the nuances of technology, such as hardware and product software of technology firms, in beginning to maximize the potential of Big Data Analytics in the firms. The findings of the paper will benefit educators in improving Big Data Analytics curricular programs to be current with the patterns of firms fruitfully initiating Big Data Analytics systems.

Pendrin is a transmembrane chloride/anion antiporter that is strongly upregulated in the airways in rhinoviral infection, asthma, cystic fibrosis and chronic rhinosinusitis. Based on its role in the regulation of airway surface liquid depth, pendrin inhibitors have potential indications for treatment of inflammatory airways diseases. Here, a completely regioselective route to tetrahydro-pyrazolopyridine pendrin inhibitors based on 1,3-diketone and substituted hydrazine condensation was been developed. Structure-activity relationships at the tetrahydropyridyl nitrogen were investigated using a focused library, establishing the privileged nature of N-phenyl ureas and improving inhibitor potency by greater than 2-fold.

The severe acute respiratory syndrome coronavirus 2 responsible for COVID-19 remains a persistent threat to mankind, especially for the immunocompromised and elderly for which the vaccine may have limited effectiveness. Entry of SARS-CoV-2 requires a high affinity interaction of the viral spike protein with the cellular receptor angiotensin-converting enzyme 2. Novel mutations on the spike protein correlate with the high transmissibility of new variants of SARS-CoV-2, highlighting the need for small molecule inhibitors of virus entry into target cells. We report the identification of such inhibitors through a robust high-throughput screen testing 15,000 small molecules from unique libraries. Several leads were validated in a suite of mechanistic assays, including whole cell SARS-CoV-2 infectivity assays. The main lead compound, calpeptin, was further characterized using SARS-CoV-1 and the novel SARS-CoV-2 variant entry assays, SARS-CoV-2 protease assays and molecular docking. This study reveals calpeptin as a potent and specific inhibitor of SARS-CoV-2 and some variants.

The benefits of Big Data Analytics are cited frequently in the literature. However, the difficulties of implementing Big Data Analytics can limit the number of organizational projects. In this study, the authors evaluate business, procedural and technical factors in the implementation of Big Data Analytics, applying a methodology program. Focusing on organizations in the health sector, the authors learn that business and procedural factors are collectively more critical than factors of technology in managing Big Data Analytics projects that attempt to contribute discernible impact; and they further learn that managing for practical results than for strategy is more evident on the projects in the sector. The study will benefit educators in improving Big Data Analytics curricula with a methodology program and will benefit practitioners in the sector in initiating systems.

The most common cystic fibrosis-causing mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) is deletion of phenylalanine at residue 508 (∆F508). The ∆F508 mutation impairs folding of nucleotide binding domain 1 (NBD1) and interfacial interactions of NBD1 and the membrane spanning domains. Here, we report a domain-targeted screen to identify ∆F508-CFTR modulators that act on NBD1. A biochemical screen for ΔF508-NBD1 cell surface expression was done in Madin-Darby canine kidney cells expressing a chimeric reporter consisting of ΔF508-NBD1, the CD4 transmembrane domain, and an extracellular horseradish peroxidase (HRP) reporter. Using a luminescence readout of HRP activity, the screen was robust with a Z' factor of 0.7. The screening of ~20,000 synthetic small molecules allowed the identification of compounds from four chemical classes that increased ∆F508-NBD1 cell surface expression by up to 4-fold; for comparison, a 12-fold increased cell surface expression was found for a wild-type NBD1 chimera. While the compounds were inactive as correctors of full-length ΔF508-CFTR, several carboxamide-benzothiophenes had potentiator activity with low micromolar EC50. Interestingly, the potentiators did not activate G551D or wild-type CFTR. Our results provide a proof of concept for a cell-based NBD1 domain screen to identify ∆F508-CFTR modulators that target the NBD1 domain.

BackgroundCurrent modulator therapies for some cystic fibrosis-causing CFTR mutants, including N1303K, have limited efficacy. We provide evidence here to support combination potentiator (co-potentiator) therapy for mutant CFTRs that are poorly responsive to single potentiators.MethodsFunctional synergy screens done on N1303K and W1282X CFTR, in which small molecules were tested with VX-770, identified arylsulfonamide-pyrrolopyridine, phenoxy-benzimidazole and flavone co-potentiators.ResultsA previously identified arylsulfonamide-pyrrolopyridine co-potentiator (ASP-11) added with VX-770 increased N1303K-CFTR current 7-fold more than VX-770 alone. ASP-11 increased by ~65% of the current of G551D-CFTR compared to VX-770, was additive with VX-770 on F508del-CFTR, and activated wild-type CFTR in the absence of a cAMP agonist. ASP-11 efficacy with VX-770 was demonstrated in primary CF human airway cell cultures having N1303K, W1282X and G551D CFTR mutations. Structure-activity studies on 11 synthesized ASP-11 analogs produced compounds with EC50 down to 0.5 μM.ConclusionsThese studies support combination potentiator therapy for CF caused by some CFTR mutations that are not effectively treated by single potentiators.

SLC26A3 (downregulated in adenoma; DRA) is a Cl-/anion exchanger expressed in the luminal membrane of intestinal epithelial cells, where it facilitates electroneutral NaCl absorption. SLC26A3 loss of function in humans or mice causes chloride-losing diarrhea. Here, we identified slc26a3 inhibitors in a screen of 50,000 synthetic small molecules done in Fischer rat thyroid (FRT) cells coexpressing slc26a3 and a genetically encoded halide sensor. Structure-activity relationship studies were done on the most potent inhibitor classes identified in the screen: 4,8-dimethylcoumarins and acetamide-thioimidazoles. The dimethylcoumarin DRAinh-A250 fully and reversibly inhibited slc26a3-mediated Cl- exchange with HCO3-, I-, and thiocyanate (SCN-), with an IC50 of ~0.2 μM. DRAinh-A250 did not inhibit the homologous anion exchangers slc26a4 (pendrin) or slc26a6 (PAT-1), nor did it alter activity of other related proteins or intestinal ion channels. In mice, intraluminal DRAinh-A250 blocked fluid absorption in closed colonic loops but not in jejunal loops, while the NHE3 (SLC9A3) inhibitor tenapanor blocked absorption only in the jejunum. Oral DRAinh-A250 and tenapanor comparably reduced signs of constipation in loperamide-treated mice, with additive effects found on coadministration. DRAinh-A250 was also effective in loperamide-treated cystic fibrosis mice. These studies support a major role of slc26a3 in colonic fluid absorption and suggest the therapeutic utility of SLC26A3 inhibition in constipation.

College curricula of engineering and information systems do not afford frequent engagement with individuals with disabilities. The authors of this research study analyzed the benefits of disability films for a community film festival of largely engineering and information systems students and individuals with developmental and intellectual disabilities. The authors learned that disability film media enables discernable engagement and advocacy of the students for the rights of individuals with disabilities. The authors also learned that the disability film media facilitates engagement and self-advocacy of the individuals for themselves. This study will be beneficial to instructors in engineering and information systems, and instructors in liberal arts, evaluating film media as an exciting method for involving students with individuals with disabilities on multidisciplinary projects of public service.