Towards a more efficient healthcare system: Opportunities and challenges caused by hospital closures amid the COVID-19 pandemic.

A substantial number of United States (U.S.) hospitals have closed in recent years. The trend of closures has accelerated during the COVID-19 pandemic, as hospitals have experienced financial hardship from reduced patient volume and elective surgery cases, as well as the thin financial margins for treating patients with COVID-19. This trend of hospital closures is concerning for patients, healthcare providers, and policymakers. In this current opinion piece, we first describe the challenges caused by hospital closures and discuss what policymakers should know based on the existing research. We then discuss unique opportunities for researchers to inform policymakers by conducting careful studies that can shed light on different implications, trade-offs, and consequences of various strategies that can be followed.

ANATOMICAL VARIABILITY OF CUTANEOUS NERVES OF ANTERIOR FEMORAL REGION IN HUMAN FETUSES.

OBJECTIVE: The aim: Is to find out the features of innervation of the skin of the anterior femoral region and the fascia lata during the fetal period of human development. PATIENTS AND METHODS: Materials and methods: The study was carried out on 64 preparations of the lower extremities of human fetuses of 4-10 months using macromicroscopic preparation and morphometry. Macropreparations of the skin nerves of the lower extremities of different age fetuses with anatomical variants were subject to photo documentation. RESULTS: Results: The features of cutaneous nerve fetal topography of the anterior femoral region and the broad fascia of the femur were revealed, their connections were established, and their layering was determined. It was found that in human fetuses, not only the lateral cutaneous femoral nerve but in most cases the branches of other nerves of the lumbar plexus, except for the obturator nerve, are directed to the skin of the anterior-lateral femur surface. The innervation of the medial femur surface is provided by the following nerve complex: obturator, femoral, saphenous and genitofemoral nerves. CONCLUSION: Conclusions: Taking into account the fact that the terminal branches of adjacent cutaneous nerves of the femoral region intersect and overlap, innervation bypasses are formed, due to which, in case of possible damage to one of the nerves, its insufficiency is compensated to a certain extent. Anastomoses were found between the cutaneous nerves, in the form of loops of various shapes and sizes, namely: between the cutaneous-fascia branches of the femoral and ilioinguinal nerves and the femoral and obturator nerves.

Inherited genetic variant predisposes to aggressive but not indolent prostate cancer.

Autopsy studies suggest that most aging men will develop lesions that, if detected clinically, would be diagnosed as prostate cancer (PCa). Most of these cancers are indolent and remain localized; however, a subset of PCa is aggressive and accounts for more than 27,000 deaths in the United States annually. Identification of factors specifically associated with risk for more aggressive PCa is urgently needed to reduce overdiagnosis and overtreatment of this common disease. To search for such factors, we compared the frequencies of SNPs among PCa patients who were defined as having either more aggressive or less aggressive disease in four populations examined in the Genetic Markers of Susceptibility (CGEMS) study performed by the National Cancer Institute. SNPs showing possible associations with disease severity were further evaluated in an additional three independent study populations from the United States and Sweden. In total, we studied 4,829 and 12,205 patients with more and less aggressive disease, respectively. We found that the frequency of the TT genotype of SNP rs4054823 at 17p12 was consistently higher among patients with more aggressive compared with less aggressive disease in each of the seven populations studied, with an overall P value of 2.1 x 10(-8) under a recessive model, exceeding the conservative genome-wide significance level. The difference in frequency was largest between patients with high-grade, non-organ-confined disease compared with those with low-grade, organ-confined disease. This study demonstrates that inherited variants predisposing to aggressive but not indolent PCa exist in the genome, and suggests that the clinical potential of such variants as potential early markers for risk of aggressive PCa should be evaluated.

Clinical practice of new nurse graduates in Lebanon: challenges and perspectives through the eyes of preceptors.

New nurse graduates continue to experience difficulty balancing their preparation for practice with the expectations of the workplace. Few studies have explored the transition practices of nurse graduates through the challenges that they experience. This article presents the findings of a research study that explored the perceptions of preceptors regarding the clinical practice of nurse graduates using the qualitative multiple case study design. Twenty preceptors, selected from three recognized hospitals in Beirut, Lebanon, underwent semistructured interviews. Interview questions were based on an extensive literature review and on Tanner's (2006) judgment dimensions to categorize transition practices. An exhaustive discussion of the practices led to the identification of major themes that illustrate the clinical experiences of new nurse graduates: (1) inventory of competencies, (2) learning experience, (3) technical and theoretical mysteries, and (4) challenge of one's potential. The themes provide directives that curriculum leaders and executive nurses can use to plan initiatives that assist in the effective transition of new nurse graduates to the professional role.

Research priorities to reduce the impact of COVID-19 in low- and middle-income countries.

Background: The COVID-19 pandemic has caused disruptions to the functioning of societies and their health systems. Prior to the pandemic, health systems in low- and middle-income countries (LMIC) were particularly stretched and vulnerable. The International Society of Global Health (ISoGH) sought to systematically identify priorities for health research that would have the potential to reduce the impact of the COVID-19 pandemic in LMICs. Methods: The Child Health and Nutrition Research Initiative (CHNRI) method was used to identify COVID-19-related research priorities. All ISoGH members were invited to participate. Seventy-nine experts in clinical, translational, and population research contributed 192 research questions for consideration. Fifty-two experts then scored those questions based on five pre-defined criteria that were selected for this exercise: 1) feasibility and answerability; 2) potential for burden reduction; 3) potential for a paradigm shift; 4) potential for translation and implementation; and 5) impact on equity. Results: Among the top 10 research priorities, research questions related to vaccination were prominent: health care system access barriers to equitable uptake of COVID-19 vaccination (ranked 1st), determinants of vaccine hesitancy (4th), development and evaluation of effective interventions to decrease vaccine hesitancy (5th), and vaccination impacts on vulnerable population/s (6th). Health care delivery questions also ranked highly, including: effective strategies to manage COVID-19 globally and in LMICs (2nd) and integrating health care for COVID-19 with other essential health services in LMICs (3rd). Additionally, the assessment of COVID-19 patients' needs in rural areas of LMICs was ranked 7th, and studying the leading socioeconomic determinants and consequences of the COVID-19 pandemic in LMICs using multi-faceted approaches was ranked 8th. The remaining questions in the top 10 were: clarifying paediatric case-fatality rates (CFR) in LMICs and identifying effective strategies for community engagement against COVID-19 in different LMIC contexts. Interpretation: Health policy and systems research to inform COVID-19 vaccine uptake and equitable access to care are urgently needed, especially for rural, vulnerable, and/or marginalised populations. This research should occur in parallel with studies that will identify approaches to minimise vaccine hesitancy and effectively integrate care for COVID-19 with other essential health services in LMICs. ISoGH calls on the funders of health research in LMICs to consider the urgency and priority of this research during the COVID-19 pandemic and support studies that could make a positive difference for the populations of LMICs.

Teaching domains of clinical instruction from the experiences of preceptors.

Clinical teaching is vital to prepare nursing students for the role, build learning experiences, and ease transition. This study aimed at exploring the pedagogical principles that guide clinical educators in teaching undergraduate nursing students. The descriptive, qualitative, multiple-case study design, guided by the cognitive task analysis research, helped gain insights into how 18 nurse preceptors provided clinical instruction. The design entailed direct observation of preceptors while teaching students followed by interviews. Observation notes and interview data were analyzed using pattern identification and data thematization. Teaching practices of preceptors were grouped into four domains: (1) partnership, (2) competence-building, (3) nurturing, and (4) meaning-making. The domains represent the pedagogical principles that underpin the preceptors' instructional practice. While the focus of instruction was on competence-building of students, the meaning-making domain was found subordinated by most of preceptors. The findings support prior recommendations that expertise and proficiency must not be the sole agents for selecting preceptors. This study will significantly contribute to the advancement of nursing education through an improved education system that incorporates the four domains in clinical instruction in general, and preceptor preparation in specific. The emergent domains contribute to setting the framework of clinical instruction.

Inhibition of thioredoxin-interacting protein and inflammasome assembly using verapamil mitigates diabetic retinopathy and pancreatic injury.

It has been previously demonstrated by our group that genetic inhibition of thioredoxin-interacting-protein (TXNIP) preserved retinal neuronal function in chemically-induced retinopathy. Moreover, elevated intracellular levels of TXNIP and calcium ions play important roles in hyperglycemia-induced oxidative stress and inflammation. Current study aimed to appraise the potential therapeutic benefits of pharmacological inhibition of TXNIP using verapamil in diabetic retinopathy. Diabetic retinopathy was assessed in type-1 diabetes rat model induced by a single intravenous injection of streptozotocin (45 mg/kg), with or without daily treatment with verapamil (10 mg/kg, oral) for 4 months. Verapamil treatment commenced 48 h post-streptozotocin insult and continued for 16 weeks. Untreated diabetic rats exhibited higher expression of toll-like-receptor-4 (TLR4), TXNIP, nucleotide-binding domain-like receptor protein-3 (NLRP3), caspase-1, cytochrome-c, and ssDNA as assessed immunohistochemically in both retinal and pancreatic tissues 16 weeks post-diabetes induction. This was associated with a reduced thioredoxin reductase (Trx-R) activity, increased release of TNF-α and IL-1ß into vitreous fluid along with retinal ganglion cell (RGC) loss, pancreatic islets shrinkage, and enhanced CD34 expression. The treatment with verapamil enhanced Trx-R activity, significantly inhibited TLR4 mediated NLRP3-inflammasome assembly with subsequent diminishing of inflammatory markers (TNF-α and IL-1ß) release into the vitreous, suppression of pathological angiogenesis, and preservation of RGC count and pancreatic islets diameter. Current study showed that using the calcium channel blocker, verapamil, interferes with the pathogenesis of diabetic retinopathy and pancreatic islets damage at multiple levels mainly through the inhibition of TLR4, TXNIP and NLRP3-inflammasome, suggesting its promising role as an anti-diabetic and a neuroprotective agent.

A metabolomic endotype of bioenergetic dysfunction predicts mortality in critically ill patients with acute respiratory failure.

Acute respiratory failure (ARF) requiring mechanical ventilation, a complicating factor in sepsis and other disorders, is associated with high morbidity and mortality. Despite its severity and prevalence, treatment options are limited. In light of accumulating evidence that mitochondrial abnormalities are common in ARF, here we applied broad spectrum quantitative and semiquantitative metabolomic analyses of serum from ARF patients to detect bioenergetic dysfunction and determine its association with survival. Plasma samples from surviving and non-surviving patients (N = 15/group) were taken at day 1 and day 3 after admission to the medical intensive care unit and, in survivors, at hospital discharge. Significant differences between survivors and non-survivors (ANOVA, 5% FDR) include bioenergetically relevant intermediates of redox cofactors nicotinamide adenine dinucleotide (NAD) and NAD phosphate (NADP), increased acyl-carnitines, bile acids, and decreased acyl-glycerophosphocholines. Many metabolites associated with poor outcomes are substrates of NAD(P)-dependent enzymatic processes, while alterations in NAD cofactors rely on bioavailability of dietary B-vitamins thiamine, riboflavin and pyridoxine. Changes in the efficiency of the nicotinamide-derived cofactors' biosynthetic pathways also associate with alterations in glutathione-dependent drug metabolism characterized by substantial differences observed in the acetaminophen metabolome. Based on these findings, a four-feature model developed with semi-quantitative and quantitative metabolomic results predicted patient outcomes with high accuracy (AUROC = 0.91). Collectively, this metabolomic endotype points to a close association between mitochondrial and bioenergetic dysfunction and mortality in human ARF, thus pointing to new pharmacologic targets to reduce mortality in this condition.

Genetic variants and family history predict prostate cancer similar to prostate-specific antigen.

PURPOSE: Although prostate-specific antigen (PSA) is the best biomarker for predicting prostate cancer, its predictive performance needs to be improved. Results from the Prostate Cancer Prevention Trial revealed the overall performance measured by the areas under curve of the receiver operating characteristic at 0.68. The goal of the present study is to assess the ability of genetic variants as a PSA-independent method to predict prostate cancer risk. EXPERIMENTAL DESIGN: We systematically evaluated all prostate cancer risk variants that were identified from genome-wide association studies during the past year in a large population-based prostate cancer case-control study population in Sweden, including 2,893 prostate cancer patients and 1,781 men without prostate cancer. RESULTS: Twelve single nucleotide polymorphisms were independently associated with prostate cancer risk in this Swedish study population. Using a cutoff of any 11 risk alleles or family history, the sensitivity and specificity for predicting prostate cancer were 0.25 and 0.86, respectively. The overall predictive performance of prostate cancer using genetic variants, family history, and age, measured by areas under curve was 0.65 (95% confidence interval, 0.63-0.66), significantly improved over that of family history and age (0.61%; 95% confidence interval, 0.59-0.62; P = 2.3 x 10(-10)). CONCLUSION: The predictive performance for prostate cancer using genetic variants and family history is similar to that of PSA. The utility of genetic testing, alone and in combination with PSA levels, should be evaluated in large studies such as the European Randomized Study for Prostate Cancer trial and Prostate Cancer Prevention Trial.

Rethinking clinical instruction through the zone of proximal development.

BACKGROUND: The complexity of the learning environment and intricacy of nursing tasks make it difficult for students to learn without the assistance of an expert. Teaching in the zone of proximal development (ZPD) aims at positioning learners in the zone of what they can do and develop with assistance to reach full potential and independence. ZPD is deemed essential to understand how teaching and learning take place; however, its implications for clinical educators are limited and need further exploration. OBJECTIVES: This research study aimed at exploring the instructional strategies that preceptors use to guide and support the development of undergraduate nursing students, from what they are capable of doing with assistance to what they can become and do independently. DESIGN: The qualitative multiple case study research design was used to gain insights into the teaching experiences of 18 nurse preceptors situated in three recognized hospitals in Lebanon. METHODS: Each preceptor was interviewed face-to-face using questions that were developed from a three-hour observation. Vygotsky's learning principles formed the reference point for this study. Analytic induction and constant comparison of preceptors' responses were applied throughout the study to unravel assisted strategies that target the potential learning zones of the student. RESULTS: Three assumptions emerged from the data to underpin the preceptors' assistive strategies that help move learners from a cannot-do-level to can do independently. The assumptions are: (1) learning from clinical experience, (2) teaching beyond student ability, and (3) teaching for autonomy. In-depth analysis of both assumptions and strategies that focus instruction within each student's ZPD converged on a framework of three constructs: differentiated instruction, instructional scaffolding, and influencing a positive learning environment. CONCLUSION: It is imperative that clinical educators be most receptive to instruction that targets the student's ZPD, as the zone represents a potential phase in student learning. This study provides a ZPD framework for intensifying learning gains from clinical practice.

Development and Evaluation of the Chromatic Behavior of an Intelligent Packaging Material Based on Cellulose Acetate Incorporated with Polydiacetylene for an Efficient Packaging.

Global growth of the food industry and the demand for new products with natural characteristics, safe conditions and traceability have driven researches for the development of technologies such as intelligent packaging, capable to fulfil those needs. Polydiacetylene (PDA) is a synthetic material that has been highlighted in research field as a sensor substance, which can be used to produce intelligent packaging capable to detect chemical or biochemical changes in foods and in their environment due to PDA's color transition from blue to red. This work focused on the development and optimization of an intelligent packaging constituted of a polymeric matrix of cellulose acetate-based incorporated with PDA as the substance sensor. Cellulose acetate films (3% wt.) were developed by a casting method, and the amounts of triethyl citrate plasticizer (TEC) (0-25% wt. of cellulose-acetate) and PDA (0-60 mg) were analyzed to optimize the conditions for the best color transitioning at this study range. The compound amounts incorporated into polymeric matrices were established according to Central Composite Designs (CCD). Three more design variables were analyzed, such as the polymerization time of PDA under UV light exposition (0-60 min), pH values (4-11) and temperature exposure on the film (0-100 °C), important factors on the behavior of PDA's color changing. In this study, film thickness and film color coordinates were measured in order to study the homogeneity and the color transitioning of PDA films under different pH and temperature conditions, with the purpose of maximizing the color changes through the optimization of PDA and TEC concentrations into the cellulose acetate matrix and the polymerization degree trigged by UV light irradiation. The optimal film conditions were obtained by adding 50.48 g of PDA and 10% of TEC, polymerization time of 18 min under UV light, at 100 °C ± 2 °C of temperature exposure. The changes in pH alone did not statistically influence the color coordinates measured at the analyzed ratio; however, variations in pH associated with other factors had a significant effect on visual color changes, and observations were described. PDA films were optimized to maximize color change in order to obtain a cheap and simple technology to produce intelligent packaging capable to monitor food products along the distribution chain in real time, improving the food quality control and consumer safety.

Changes in screening colonoscopy following Medicare reimbursement and cost-sharing changes.

OBJECTIVES: To compare existing algorithms for classifying screening vs diagnostic colonoscopies and to quantify the increase in screening colonoscopy rates when Medicare began reimbursement in 2001 and when the Affordable Care Act (ACA) eliminated cost-sharing. DATA SOURCES: Twenty percent random sample of fee-for-service (FFS) Medicare claims, 2000-2012. STUDY DESIGN: Using recent administrative codes as tarnished gold standards, we examined the sensitivity and specificity of five published algorithms for classifying colonoscopies and calculated annual screening colonoscopy rates. We estimated the change in rates after Medicare began reimbursement and used difference-in-differences analysis to estimate the effects of eliminating cost-sharing by comparing states with and without a mandate to cover screening colonoscopy prior to the ACA. FINDINGS: Model-based algorithms have higher sensitivity (0.53-0.99) than expert-based algorithms (0.35-0.39), but lower specificity (0.43-0.65 vs 0.79-0.88). All algorithms detected increases in screening from both Medicare's reimbursement change (range: 24-93/10 000) and the 2011 cost-sharing change (range: 1.1-34/10 000). Difference-in-difference estimates of the ACA's effect varied from 51 to 155 tests per 10 000 depending on the algorithm. CONCLUSIONS: Screening colonoscopy rates increased after eliminating cost-sharing in 2011, but the increase's size varied depending on the algorithm used to classify the indication. Improvements are needed in Medicare coding for screening.

The cost-effectiveness of medication, laser trabeculoplasty, and trabeculectomy for treatment of open-angle glaucoma in South Korea.

OBJECTIVES: Open-angle glaucoma (OAG) imposes high disease burden in South Korea. Although various effective interventions are available to manage the progression of OAG, there is limited data on the cost-effectiveness of these treatment strategies in South Korea. METHODS: Using a Markov cohort model, we evaluated the cost-effectiveness of 3 major treatment strategies (medication, laser trabeculoplasty, and trabeculectomy) for South Korean patients with OAG. We projected a 25-year time horizon to study a hypothetical cohort of 10,000 patients of age 40 with mild OAG. The outcome measures were quality-adjusted life-years (QALYs) gained, cost from the societal perspective, and the incremental cost-effectiveness ratio (ICER) of medication, laser trabeculoplasty, and trabeculectomy. Interventions were evaluated at a willingness-to-pay (WTP) threshold of 30,000,000 KRW ($29,152) per QALY gained. Deterministic and probabilistic sensitivity analyses were conducted to address the model uncertainty. RESULTS: The mean costs for medication, laser trabeculoplasty, and trabeculectomy were 29,661,740 KRW, 17,34,1342 KRW, and 22,275,438 KRW, respectively. The mean QALYs gained were 15.7, 15.3, and 14.8 for medication, laser trabeculoplasty, and trabeculectomy, respectively. Surgery was strongly dominated because it generated fewer expected QALYs but incurred greater expected cost than laser. The ICER was 30,885,179 KRW per QALY for medication versus laser trabeculoplasty. Laser was cost-effective, however, at a lower WTP threshold of 21,000,000 KRW per QALY gained or below. The results were most sensitive to the progression rates from mild to moderate glaucoma under laser treatment. CONCLUSION: Under the WTP threshold of 30,000,000 KRW per QALY, medication was cost-effective compared with laser trabeculoplasty and trabeculectomy for treating mild OAG in South Korean population. Laser, however, can be a cost-effective alternative in more resource-limited settings.

Correction: The cost-effectiveness of systematic screening for age-related macular degeneration in South Korea.

[This corrects the article DOI: 10.1371/journal.pone.0206690.].

The cost-effectiveness of systematic screening for age-related macular degeneration in South Korea.

BACKGROUND: Interventions that can facilitate early diagnosis of age-related macular degeneration (AMD) will facilitate early treatment and improve clinical outcomes but there has been concerns about additional medical costs to the health care system. An examination through a retina fundus photography by a non-specialist has been suggested as a potential cost-effective alternative to a direct examination by a specialist, but limited scientific data exists on the cost-effectiveness of screening strategies for AMD. Our objective is to conduct an economic evaluation of various population-wide screening strategies for AMD among the South Korean population. METHODS AND FINDINGS: Using a Markov cohort model, we evaluated the cost-effectiveness of four AMD screening strategies (opportunistic examination, opportunistic treatment, systematic photography, and systematic examination) in comparison with status quo (no screening) for South Korean adults. We projected a life time horizon to study a hypothetical cohort of 100,00 persons of age 40 with and without AMD at baseline. The outcome measures were quality-adjusted life-years (QALYs) gained, cost from the societal perspective, and the incremental cost-effectiveness ratio (ICER) of each strategy. Interventions were evaluated at a willingness-to-pay (WTP) threshold of 30,000,000 KRW ($27,538) per QALY gained. Deterministic and probabilistic sensitivity analyses were conducted to address the model uncertainty. Opportunistic examination was strongly dominated because it generated fewer expected QALYs but incurred greater expected cost than the other screening strategies. The mean lifetime expected costs were 289,013 KRW, 363,692 KRW, 9,351,964 KRW, and 12,309,783 KRW, and the mean QALYs gained were 37.73, 37.75, 40.47, 40.68, for no screening, opportunistic treatment, systematic photography, and systematic examination, respectively. The results were most sensitive to the utility weight of mild AMD, the probability of complication from treatment, the cost of being in mild AMD, and the probability of recovery from complication. After eliminating the two weakly dominated strategies, systematic photography was cost-effective at the ICER of 3,310,448 KRW per QALY in comparison to status quo. CONCLUSIONS: Under the WTP threshold of 30,000,000 KRW per QALY, systematic photography is cost-effective for screening AMD in South Korean adults. Systematic examination by ophthalmologists generates more expected QALY and cost compared to systematic photography.

Correction: The cost-effectiveness of systematic screening for age-related macular degeneration in South Korea.

[This corrects the article DOI: 10.1371/journal.pone.0206690.].

Context-Based Pedagogy: A Framework From Experience.

BACKGROUND: Attempts to transform teaching practice are inadvertently subjected to several hurdles, mostly attributed to the lack of a guiding framework. This study aimed at unraveling the conceptual underpinnings of the context-based pedagogy, being perceived the pedagogy that prepares professionals for future practice. METHOD: Through focus group interviews, data were collected from 16 nursing students who had case studies as the main instructional format in three major courses. The participants were divided into three focus groups, and interview questions were based on three educational parameters: the learning environment, instructional format, and instructional process. RESULTS: Initial findings revealed an array of classroom activities that characterize each parameter. An in-depth analysis of these activities converged on four concepts: (a) dynamic learning environment, (b) realism, (c) thinking dispositions, and (d) professional formation. CONCLUSION: These concepts improvise a beginning framework for educators and curriculum leaders that can be used to integrate cases in the curriculum and to facilitate the contextualization of knowledge. [J Nurs Educ. 2016;55(7):391-395.].

Differentially correlated genes in co-expression networks control phenotype transitions.

BACKGROUND: Co-expression networks are a tool widely used for analysis of "Big Data" in biology that can range from transcriptomes to proteomes, metabolomes and more recently even microbiomes. Several methods were proposed to answer biological questions interrogating these networks. Differential co-expression analysis is a recent approach that measures how gene interactions change when a biological system transitions from one state to another. Although the importance of differentially co-expressed genes to identify dysregulated pathways has been noted, their role in gene regulation is not well studied. Herein we investigated differentially co-expressed genes in a relatively simple mono-causal process (B lymphocyte deficiency) and in a complex multi-causal system (cervical cancer). METHODS: Co-expression networks of B cell deficiency (Control and BcKO) were reconstructed using Pearson correlation coefficient for two mus musculus datasets: B10.A strain (12 normal, 12 BcKO) and BALB/c strain (10 normal, 10 BcKO). Co-expression networks of cervical cancer (normal and cancer) were reconstructed using local partial correlation method for five datasets (total of 64 normal, 148 cancer). Differentially correlated pairs were identified along with the location of their genes in BcKO and in cancer networks. Minimum Shortest Path and Bi-partite Betweenness Centrality where statistically evaluated for differentially co-expressed genes in corresponding networks.    Results: We show that in B cell deficiency the differentially co-expressed genes are highly enriched with immunoglobulin genes (causal genes). In cancer we found that differentially co-expressed genes act as "bottlenecks" rather than causal drivers with most flows that come from the key driver genes to the peripheral genes passing through differentially co-expressed genes. Using in vitro knockdown experiments for two out of 14 differentially co-expressed genes found in cervical cancer (FGFR2 and CACYBP), we showed that they play regulatory roles in cancer cell growth. CONCLUSION: Identifying differentially co-expressed genes in co-expression networks is an important tool in detecting regulatory genes involved in alterations of phenotype.

Case-based learning: What traditional curricula fail to teach.

BACKGROUND: Case-based learning seeks to contextualize learning and to enhance the transition of nurses to practice. This instructional approach is gaining widespread interest in nursing education since the unfolding process emulates the work environment. Case-based learning holds great promise to the development of professional skills. An assumption that was worth researching to determine what those skills are. OBJECTIVES: This study aimed at exploring perceptions of nursing students who had completed two undergraduate nursing courses using case-based learning to be able to identify professional skills that may be gained by this instructional approach. DESIGN: The qualitative focus group research technique was used to explore the perceptions of 16 nursing students who used CBL in two adult health nursing courses in the junior year of an undergraduate nursing program in Beirut, Lebanon. The sample was divided into three groups of four to six students each. METHOD: Thematic analysis using cross-group analysis and inductive constant comparison. FINDINGS: The analyzed data converged on three learning practices that were developed by the case study approach: (a) recognizing the particulars of a clinical situation, (b) making sense of patient data and informing decisions, and (c) reflection. In-depth analysis of these practices helped unravel four professional attributes that form the tenets of case-based learning: (1) a salience of clinical knowledge, (2) multiple ways of thinking, (3) professional self-concept, and (4) professional caring. CONCLUSION: Since professional skills are developmental in nature, educational programs may play an active role in the skill acquisition process. In search of those ineffable skills, four professional attributes emerged from the study findings. Findings support concerns of higher education regarding the ability of the traditional curriculum to meet the expectations of employers at the workplace.

Reverse enGENEering of Regulatory Networks from Big Data: A Roadmap for Biologists.

Omics technologies enable unbiased investigation of biological systems through massively parallel sequence acquisition or molecular measurements, bringing the life sciences into the era of Big Data. A central challenge posed by such omics datasets is how to transform these data into biological knowledge, for example, how to use these data to answer questions such as: Which functional pathways are involved in cell differentiation? Which genes should we target to stop cancer? Network analysis is a powerful and general approach to solve this problem consisting of two fundamental stages, network reconstruction, and network interrogation. Here we provide an overview of network analysis including a step-by-step guide on how to perform and use this approach to investigate a biological question. In this guide, we also include the software packages that we and others employ for each of the steps of a network analysis workflow.