OutSingle: a novel method of detecting and injecting outliers in RNA-Seq count data using the optimal hard threshold for singular values.

MOTIVATION: Finding outliers in RNA-sequencing (RNA-Seq) gene expression (GE) can help in identifying genes that are aberrant and cause Mendelian disorders. Recently developed models for this task rely on modeling RNA-Seq GE data using the negative binomial distribution (NBD). However, some of those models either rely on procedures for inferring NBD's parameters in a nonbiased way that are computationally demanding and thus make confounder control challenging, while others rely on less computationally demanding but biased procedures and convoluted confounder control approaches that hinder interpretability. RESULTS: In this article, we present OutSingle (Outlier detection using Singular Value Decomposition), an almost instantaneous way of detecting outliers in RNA-Seq GE data. It uses a simple log-normal approach for count modeling. For confounder control, it uses the recently discovered optimal hard threshold (OHT) method for noise detection, which itself is based on singular value decomposition (SVD). Due to its SVD/OHT utilization, OutSingle's model is straightforward to understand and interpret. We then show that our novel method, when used on RNA-Seq GE data with real biological outliers masked by confounders, outcompetes the previous state-of-the-art model based on an ad hoc denoising autoencoder. Additionally, OutSingle can be used to inject artificial outliers masked by confounders, which is difficult to achieve with previous approaches. We describe a way of using OutSingle for outlier injection and proceed to show how OutSingle outperforms its competition on 16 out of 18 datasets that were generated from three real datasets using OutSingle's injection procedure with different outlier types and magnitudes. Our methods are applicable to other types of similar problems involving finding outliers in matrices under the presence of confounders. AVAILABILITY AND IMPLEMENTATION: The code for OutSingle is available at https://github.com/esalkovic/outsingle.

The sensitivity of acute myeloid leukemia cells to cytarabine is increased by suppressing the expression of Heme oxygenase-1 and hypoxia-inducible factor 1-alpha.

BACKGROUND: Acute myeloid leukemia (AML), a malignancy Often resistant to common chemotherapy regimens (Cytarabine (Ara-c) + Daunorubicin (DNR)), is accompanied by frequent relapses. Many factors are involved in causing chemoresistance. Heme Oxygenase-1 (HO-1) and Hypoxia-Inducible Factor 1-alpha (HIF-1α) are two of the most well-known genes, reported to be overexpressed in AML and promote resistance against chemotherapy according to several studies. The main chemotherapy agent used for AML treatment is Ara-c. We hypothesized that simultaneous targeting of HO-1 and HIF-1α could sensitize AML cells to Ara-c. METHOD: In this study, we used our recently developed, Trans-Activator of Transcription (TAT) - Chitosan-Carboxymethyl Dextran (CCMD) - Poly Ethylene Glycol (PEG) - Nanoparticles (NPs), to deliver Ara-c along with siRNA molecules against the HO-1 and HIF-1α genes to AML primary cells (ex vivo) and cell lines including THP-1, KG-1, and HL-60 (in vitro). Subsequently, the effect of the single or combinational treatment on the growth, proliferation, apoptosis, and Reactive Oxygen Species (ROS) formation was evaluated. RESULTS: The designed NPs had a high potential in transfecting cells with siRNAs and drug. The results demonstrated that treatment of cells with Ara-c elevated the generation of ROS in the cells while decreasing the proliferation potential. Following the silencing of HO-1, the rate of apoptosis and ROS generation in response to Ara-c increased significantly. While proliferation and growth inhibition were considerably evident in HIF-1α-siRNA-transfected-AML cells compared to cells treated with free Ara-c. We found that the co-inhibition of genes could further sensitize AML cells to Ara-c treatment. CONCLUSIONS: As far as we are aware, this study is the first to simultaneously inhibit the HO-1 and HIF-1α genes in AML using NPs. It can be concluded that HO-1 causes chemoresistance by protecting cells from ROS damage. Whereas, HIF-1α mostly exerts prolific and direct anti-apoptotic effects. These findings imply that simultaneous inhibition of HO-1 and HIF-1α can overcome Ara-c resistance and help improve the prognosis of AML patients.

Umbrella review and network meta-analysis of diagnostic imaging test accuracy studies in Differentiating between brain tumor progression versus pseudoprogression and radionecrosis.

PURPOSE: In this study we gathered and analyzed the available evidence regarding 17 different imaging modalities and performed network meta-analysis to find the most effective modality for the differentiation between brain tumor recurrence and post-treatment radiation effects. METHODS: We conducted a comprehensive systematic search on PubMed and Embase. The quality of eligible studies was assessed using the Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) instrument. For each meta-analysis, we recalculated the effect size, sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio from the individual study data provided in the original meta-analysis using a random-effects model. Imaging technique comparisons were then assessed using NMA. Ranking was assessed using the multidimensional scaling approach and by visually assessing surface under the cumulative ranking curves. RESULTS: We identified 32 eligible studies. High confidence in the results was found in only one of them, with a substantial heterogeneity and small study effect in 21% and 9% of included meta-analysis respectively. Comparisons between MRS Cho/NAA, Cho/Cr, DWI, and DSC were most studied. Our analysis showed MRS (Cho/NAA) and 18F-DOPA PET displayed the highest sensitivity and negative likelihood ratios. 18-FET PET was ranked highest among the 17 studied techniques with statistical significance. APT MRI was the only non-nuclear imaging modality to rank higher than DSC, with statistical insignificance, however. CONCLUSION: The evidence regarding which imaging modality is best for the differentiation between radiation necrosis and post-treatment radiation effects is still inconclusive. Using NMA, our analysis ranked FET PET to be the best for such a task based on the available evidence. APT MRI showed promising results as a non-nuclear alternative.

Higher expression of SALL4-A isoform is correlated with worse outcomes and progression of the disease in subtype of testicular germ cell tumours.

BACKGROUND: The transcription factor SALL4 is associated with embryonic pluripotency and has proposed as a novel immunohistochemistry (IHC) marker for diagnosing germ cell tumours. SALL4 comprises three isoforms, and SALL4-A being the full-length isoform. Studying its isoforms could revolutionize testicular cancer prognosis and subtype differentiation. METHODS: The expression and clinical significance of isoform 'A' of SALL4 was evaluated in 124 testicular germ cell tumours (TGCTs) subtypes, adjacent 67 normal tissues and 22 benign tumours, using immunohistochemistry on tissue microarrays (TMA). RESULTS: A statistically significant higher expression of nuclear and cytoplasmic SALL4-A was detected in TGCTs histological subtypes and benign tumours compared to the normal tissues. Seminoma and yolk sac tumours had the highest nuclear and cytoplasmic expression of SALL4-A. A significant correlation was detected between the higher nuclear expression of SALL4-A and increased pT stages (P = 0.026) in seminomas. Whereas in embryonal carcinomas, cytoplasmic expression of SALL4-A was associated with the tumour recurrence (P = 0.04) and invasion of the epididymis (P = 0.011). CONCLUSIONS: SALL4-A isoform expression in the cytoplasm and nucleus of TGCTs may be associated with histological differentiation. In the seminoma subtype of TGCTs, higher expression of SALL4-A may be used as a predictive indicator of poorer outcomes and prognosis.

Occupational Preferences, Childhood Behavior, and Openness: The Role of Sex, Sexual Orientation, and Gender Identity in Iran.

Previous research suggests that both same-sex attraction and the personality trait "openness" are associated with sex-atypical preferences and behaviors. Here, we examined the links between adulthood occupational preferences, childhood play behavior, and openness among Iranian cisgender gynephilic males (n = 228), cisgender ambiphilic males (n = 48), cisgender androphilic males (n = 178), transgender androphilic males (n = 58), cisgender androphilic females (n = 226), cisgender ambiphilic females (n = 94), cisgender gynephilic females (n = 31), and transgender gynephilic females (n = 121) from Iran. Cisgender and transgender same-sex attracted males and females exhibited sex-atypical occupational preferences with the latter group showing even more sex-atypicality than the former. The personality trait openness did not differ between cisgender groups. Transgender androphilic males had a significantly higher mean score for openness compared to cisgender androphilic females and transgender gynephilic females, whereas transgender gynephilic females had a significantly lower mean score compared to cisgender androphilic males. In both males and females, childhood sex-atypicality, same-sex attraction, and openness were associated with sex-atypical occupational preferences. Our findings from Iran provides cross-cultural support for interconnectedness of childhood and adulthood sex-atypicality, openness, and same-sex attraction in males and females who are cisgender and transgender.

The effect of service-based learning on health education competencies of students in community health nursing internships.

AIM: This study investigated the impact of service-based learning on the health education competencies of students in community health nursing internships. community health nursing internship is one of the areas where students acquire health education competencies. Studies have shown that some students have poor health education competencies, and new educational interventions, such as service-based learning, can help improve their competencies. METHOD: This quasi-experimental study was conducted in 2021-2022. The participants were final-year nursing students affiliated to Kerman University of Medical Sciences. All participants (n = 72) were selected via the census method and randomly divided into intervention and control groups (36 participants in each group). The students in the intervention group attended a service-based learning program for 20 days. The data were collected before and one month after intervention using a 48-item health education qualification questionnaire. The collected data were analyzed using SPSS22 software. RESULTS: The results showed that the mean health education competencies scores were lower before intervention in the intervention and control group (165.75 ± 23.09) (170.16 ± 28.58)(p > 0.05). There was no significant difference between the two groups in terms of their mean scores on health education competencies(p > 0.05). The health education competencies score increased significantly for the participants in the intervention group (191.58 ± 28.35) compared to the control group (165.97 ± 28.11) after intervention. CONCLUSION: Nursing administrators and professors need to take effective steps to empower nursing students as much as possible and incorporate service-based learning techniques in clinical education programs for nursing students.

Prospective Randomized Trial of Na/K Citrate for the Prevention of Contrast-Induced Nephropathy in High-risk Patients.

Background: Contrast-induced nephropathy (CIN) or contrast-induced acute kidney injury (CI-AKI) refers to an acute kidney injury (AKI) occurring after exposure to contrast media, commonly used in diagnostic procedures or therapeutic angiographic interventions. Recently, Na/K citrate, used for urine alkalinization, has been assessed for preventing CIN. This experiment evaluated Na/K citrate's efficacy in preventing CIN in high-risk patients undergoing cardiac catheterization. Methods: A prospective randomized clinical trial involved 400 patients with moderate- to high-risk factors for CIN undergoing elective percutaneous coronary intervention (PCI). They were randomly assigned to either the control or Na/K citrate groups. The Na/K citrate group (n = 200) received a 5 g Na/K citrate solution diluted in 200 mL water 2 hours before and 4 hours after the first administration, along with intravenous hydration for 2 hours before and 6 hours after the procedure. In contrast, the control group (n = 200) received only intravenous hydration. Serum creatinine (SCr) levels were measured before contrast exposure and 48 hours afterward. CIN was defined as a 25% increase in serum creatinine (SCr) or > 0.5 mg/dL 48 hours after contrast administration. The significance level was set at P ˂ 0.05. Results: CIN was observed in 33 patients (16.5%) in the control group and 6 patients (3%) in the Na/K citrate group. The incidence of CIN was found to have a significant difference between the 2 groups 48 hours after receiving the radiocontrast agent (P < 0.001). Conclusion: Our results show that Na/K citrate is helpful and substantially reduces the incidence of CIN.

Deep learning in ovarian cancer diagnosis: a comprehensive review of various imaging modalities.

Ovarian cancer poses a major worldwide health issue, marked by high death rates and a deficiency in reliable diagnostic methods. The precise and prompt detection of ovarian cancer holds great importance in advancing patient outcomes and determining suitable treatment plans. Medical imaging techniques are vital in diagnosing ovarian cancer, but achieving accurate diagnoses remains challenging. Deep learning (DL), particularly convolutional neural networks (CNNs), has emerged as a promising solution to improve the accuracy of ovarian cancer detection. This systematic review explores the role of DL in improving the diagnostic accuracy for ovarian cancer. The methodology involved the establishment of research questions, inclusion and exclusion criteria, and a comprehensive search strategy across relevant databases. The selected studies focused on DL techniques applied to ovarian cancer diagnosis using medical imaging modalities, as well as tumour differentiation and radiomics. Data extraction, analysis, and synthesis were performed to summarize the characteristics and findings of the selected studies. The review emphasizes the potential of DL in enhancing the diagnosis of ovarian cancer by accelerating the diagnostic process and offering more precise and efficient solutions. DL models have demonstrated their effectiveness in categorizing ovarian tissues and achieving comparable diagnostic performance to that of experienced radiologists. The integration of DL into ovarian cancer diagnosis holds the promise of improving patient outcomes, refining treatment approaches, and supporting well-informed decision-making. Nevertheless, additional research and validation are necessary to ensure the dependability and applicability of DL models in everyday clinical settings.

Recent advances on high-efficiency of microRNAs in different types of lung cancer: a comprehensive review.

Carcinoma of the lung is among the most common types of cancer globally. Concerning its histology, it is categorized as a non-small cell carcinoma (NSCLC) and a small cell cancer (SCLC) subtype. MicroRNAs (miRNAs) are a member of non-coding RNA whose nucleotides range from 19 to 25. They are known to be critical regulators of cancer via epigenetic control of oncogenes expression and by regulating tumor suppressor genes. miRNAs have an essential function in a tumorous microenvironment via modulating cancer cell growth, metastasis, angiogenesis, metabolism, and apoptosis. Moreover, a wide range of information produced via several investigations indicates their tumor-suppressing, oncogenic, diagnostic assessment, and predictive marker functions in different types of lung malignancy. miRNA mimics or anti-miRNAs can be transferred into a lung cancer cell, with possible curative implications. As a result, miRNAs hold promise as targets for lung cancer treatment and detection. In this study, we investigate the different functions of various miRNAs in different types of lung malignancy, which have been achieved in recent years that show the lung cancer-associated regulation of miRNAs expression, concerning their function in lung cancer beginning, development, and resistance to chemotherapy, also the probability to utilize miRNAs as predictive biomarkers for therapy reaction.

The prognostic and therapeutic potential of HO-1 in leukemia and MDS.

BACKGROUND: Heme oxygenase-1 (HO-1), a heme-degrading enzyme, is proven to have anti-apoptotic effects in several malignancies. In addition, HO-1 is reported to cause chemoresistance and increase cell survival. Growing evidence indicates that HO-1 contributes to the course of hematological malignancies as well. Here, the expression pattern, prognostic value, and the effect of HO-1 targeting in HMs are discussed. MAIN BODY: According to the recent literature, it was discovered that HO-1 is overexpressed in myelodysplastic syndromes (MDS), chronic myeloid leukemia (CML), acute myeloblastic leukemia (AML), and acute lymphoblastic leukemia (ALL) cells and is associated with high-risk disease. Furthermore, in addition to HO-1 expression by leukemic and MDS cells, CML, AML, and ALL leukemic stem cells express this protein as well, making it a potential target for eliminating minimal residual disease (MRD). Moreover, it was concluded that HO-1 induces tumor progression and prevents apoptosis through various pathways. CONCLUSION: HO-1 has great potential in determining the prognosis of leukemia and MDS patients. HO-1 induces resistance to several chemotherapeutic agents as well as tyrosine kinase inhibitors and following its inhibition, chemo-sensitivity increases. Moreover, the exact role of HO-1 in Chronic Lymphocytic Leukemia (CLL) is yet unknown. While findings illustrate that MDS and other leukemic patients could benefit from HO-1 targeting. Future studies can help broaden our knowledge regarding the role of HO-1 in MDS and leukemia. Video abstract.

Graphene oxide nanoarchitectures in cancer therapy: Drug and gene delivery, phototherapy, immunotherapy, and vaccine development.

The latest advancements in oncology involves the creation of multifunctional nanostructures. The integration of nanoparticles into the realm of cancer therapy has brought about a transformative shift, revolutionizing the approach to addressing existing challenges and limitations in tumor elimination. This is particularly crucial in combating the emergence of resistance, which has significantly undermined the effectiveness of treatments like chemotherapy and radiotherapy. GO stands as a carbon-derived nanoparticle that is increasingly finding utility across diverse domains, notably in the realm of biomedicine. The utilization of GO nanostructures holds promise in the arena of oncology, enabling precise transportation of drugs and genetic material to targeted sites. GO nanomaterials offer the opportunity to enhance the pharmacokinetic behavior and bioavailability of drugs, with documented instances of these nanocarriers elevating drug accumulation at the tumor location. The GO nanostructures encapsulate genes, shielding them from degradation and facilitating their uptake within cancer cells, thereby promoting efficient gene silencing. The capability of GO to facilitate phototherapy has led to notable advancements in reducing tumor progression. By PDT and PTT combination, GO nanomaterials hold the capacity to diminish tumorigenesis. GO nanomaterials have the potential to trigger both cellular and innate immunity, making them promising contenders for vaccine development. Additionally, types of GO nanoparticles that respond to specific stimuli have been applied in cancer eradication, as well as for the purpose of cancer detection and biomarker diagnosis. Endocytosis serves as the mechanism through which GO nanomaterials are internalized. Given these advantages, the utilization of GO nanomaterials for tumor elimination comes highly recommended.

The effect of scenario-based training on the Core competencies of nursing students: a semi-experimental study.

INTRODUCTION: Competency is defined as the variety of skills and knowledge required to perform a specific task. Due to the specificity of pediatric nursing, students face some challenges in acquiring core competencies. Therefore, the use of new training methods in pediatric nursing is necessary. One of the modern learning methods is learning based on clinical scenarios. Thus, this study aimed to investigate the effect of scenario-based education on the core competencies of nursing students. METHOD: This quasi-experimental study employed a pre-test and post-test design. All participants (n = 72) were selected via the census method and randomly divided into intervention (N = 33) and control groups (N = 40). The data were collected using a demographic information questionnaire and the Nursing Students' Clinical Competencies Questionnaire. Before the intervention, both groups completed the pre-tests. After one month, the students in both groups completed post-tests. RESULTS: The average score of core competencies for the students in the intervention group after the training (247.05, SD = 36.48) increased compared to before the intervention (229.05, SD = 36.58) (P > 0.05). The average score of the core competencies for the students in the control group after the training was 240.76 (SD = 35.36) compared to 235.56 (SD = 27.94) before the intervention, with no significant difference (P < 0.05). The independent t-test did not show a significant difference between the control and intervention groups before and after the intervention (P > 0.05). CONCLUSION: The results indicated the effectiveness of scenario-based training on the core competencies of students in the intervention group. Accordingly, nursing administrators and professors are recommended to incorporate new scenario-based teaching and learning methods in educational programs of universities. It is also necessary to conduct more research into the effectiveness of this method in combination with other training methods like team-based and problem-based training.

SNPs of ACE1 (rs4343) and ACE2 (rs2285666) genes are linked to SARS-CoV-2 infection but not with the severity of disease.

COVID-19 and the renin-angiotensin system (RAS) are linked by angiotensin-converting enzyme 2 (ACE2), a key enzyme in RAS that has been validated as a SARS-CoV-2 receptor. Functional ACE1/ACE2 gene polymorphisms may lead to the imbalance between ACE/ACE2 ratio and thus generating RAS imbalance that is associated with higher degrees of lung damage in ARDS that may contribute to the COVID-19 infection outcome. Herein, we investigated the role of RAS gene polymorphisms, ACE1 (A2350G) and ACE2 (G8790A) as risk predictors for susceptibility and severity of COVID-19 infection. A total of 129 included: negative controls without a history of COVID-19 infection (n = 50), positive controls with a history of COVID-19 infection who were not hospitalized (n = 35), and patients with severe COVID-19 infection who were hospitalized in the intensive care unit (n = 44). rs4343 of ACE and rs2285666 of ACE2 were genotyped using PCR-RFLP method. Our results indicated that susceptibility to COVID-19 infection was associated with age, GG genotype of A2350G (Pa = 0.01; OR 4.7; 95% CI 1.4-15.1 and Pc = 0.040; OR 2.5; 95% CI 1.05-6.3) and GG genotype of G8790A (Pa = 0.044; OR 6.17; 95% CI 1.05-35.71 and Pc = 0.0001; OR 5.5; 95% CI 2.4-12.4). The G allele of A2350G (Pa = 0.21; OR 1.74; 95% CI 0.73-4.17 and Pc = 0.007; OR 2.1; 95% CI 1.2-3.5) and G allele of G8790A (Pa = 0.002; OR 4.26; 95% CI 1.7-10.65 and Pc = 0.0001; OR 4.7; 95% CI 2.4-9.2) were more frequent in ICU-admitted patients and positive control group. Also lung involvement due to COVID-19 infection was associated with age and the comorbidities such as diabetes. In conclusion, our findings support the association between the wild genotype (GG) of ACE2 and homozygote genotype (GG) of ACE1 and sensitivity to COVID-19 infection, but not its severity. However, confirmation of this hypothesis requires further studies with more participants.

Production and characterization of a new specific monoclonal antibody against A-isoform of SALL4: A novel emerging testicular cancer marker.

SALL4 transcription factor plays an important role to maintain the pluripotent and self-renewal of embryonic stem cells. It contributes to the growth of many cancers and embryonic development. With the exception of spermatogonia, SALL4 expression is silenced in most adult tissues after birth; nevertheless, it is re-expressed in a subset of different solid malignancies. SALL4 is a new, precise biomarker for testicular germ cell cancers that was just introduced. The whole isoform of SALL4 is called SALL4-A. Regarding the lack of antibody against human SALL4 isoforms, the pattern of expression, the role of each isoform remain unknown. Furthermore, in isoform specific evaluations, we aimed, for the first time, to produce and characterize mAb against human SALL4-A. Immunization of mice were performed with a selected 33-mer synthetic peptide of SALL4-A conjugated with KLH. Hybridoma cells were screened by ELISA for positive reactivity with SALL4-A peptide. From the ascites fluid of mice that had been injected with hybridoma cells, anti-SALL4-A mAbs were isolated using a protein G column. Reactivity of the mAbs was evaluated using the peptide and SALL4-A recombinant protein by ELISA and IHC on testicular cancer tissue as positive control, and normal kidney, stomach and prostate tissues as negative control. The produced mAb could well detect SALL4-A in testicular cancer tissues using IHC, while the reactivity was negative in normal kidney, stomach and prostate tissues. Using ELISA, the mAb affinity for the peptide and SALL4-A recombinant protein was assessed, and it was shown to be reasonably high. The mAb detected SALL4-A in nucleus and cytoplasm of several cancer cells and spermatogonia in testicular cancer tissue. In addition, it could recognize SALL4-A recombinant protein. Our produced monoclonal antibody against isoform-A of human SALL4 can specifically recognize SALL4-A using either IHC or ELISA. We hope that this mAb could help researchers in isoform-specific study of human SALL4.

Caps Captioning: A Modern Image Captioning Approach Based on Improved Capsule Network.

In image captioning models, the main challenge in describing an image is identifying all the objects by precisely considering the relationships between the objects and producing various captions. Over the past few years, many methods have been proposed, from an attribute-to-attribute comparison approach to handling issues related to semantics and their relationships. Despite the improvements, the existing techniques suffer from inadequate positional and geometrical attributes concepts. The reason is that most of the abovementioned approaches depend on Convolutional Neural Networks (CNNs) for object detection. CNN is notorious for failing to detect equivariance and rotational invariance in objects. Moreover, the pooling layers in CNNs cause valuable information to be lost. Inspired by the recent successful approaches, this paper introduces a novel framework for extracting meaningful descriptions based on a parallelized capsule network that describes the content of images through a high level of understanding of the semantic contents of an image. The main contribution of this paper is proposing a new method that not only overrides the limitations of CNNs but also generates descriptions with a wide variety of words by using Wikipedia. In our framework, capsules focus on the generation of meaningful descriptions with more detailed spatial and geometrical attributes for a given set of images by considering the position of the entities as well as their relationships. Qualitative experiments on the benchmark dataset MS-COCO show that our framework outperforms state-of-the-art image captioning models when describing the semantic content of the images.

The comprehensiveness and comprehensibility of publicly-available, state-approved advance directive documents.

The COVID-19 pandemic has increased attention to end-of-life decision-making and advance care planning. Advance directives (ADs) are documents that express an individual's wishes regarding their medical care if they are incapacitated and may appoint someone to make decisions for them. The purpose of the current study was to evaluate the comprehensiveness and comprehensibility of the widely available state-approved AD documents provided to the public online. Their content was coded using a grounded theory approach, and the reading level of the documents was assessed. Preferences related to important issues, such as pain relief, were commonly included (92.2% of forms), but other issues, such as whether someone would approve of artificial respiration (39.2%) or CPR (35.3%), were less often addressed. The average reading level of the forms (M = grade 7.64; SD = 1.28) was above the recommended 5th grade level. Overall, there was meaningful variability in the comprehensiveness and comprehensibility of AD documents, suggesting incompatibility for those recording their end-of-life preferences across states and the need for future work to increase their user-friendliness and ability to record authentic advance care wishes.

Potential biomarkers for testicular germ cell tumour: Risk assessment, diagnostic, prognostic and monitoring of recurrence.

Testicular germ cell tumour (TGCT) is considered a relatively rare malignancy usually occurring in young men between 15 and 35 years of age, and both genetic and environmental factors contribute to its development. The majority of patients are diagnosed in an early-stage of TGCTs with an elevated 5-year survival rate after therapy. However, approximately 25% of patients show an incomplete response to chemotherapy or tumours relapse. The current therapies are accompanied by several adverse effects, including infertility. Aside from classical serum biomarker, many studies reported novel biomarkers for TGCTs, but without proper validation. Cancer cells share many similarities with embryonic stem cells (ESCs), and since ESC genes are not transcribed in most adult tissues, they could be considered ideal candidate targets for cancer-specific diagnosis and treatment. Added to this, several microRNAs (miRNA) including miRNA-371-3p can be further investigated as a molecular biomarker for diagnosis and monitoring of TGCTs. In this review, we will illustrate the findings of recent investigations in novel TGCTs biomarkers applicable for risk assessment, screening, diagnosis, prognosis, prediction and monitoring of the relapse.

Protein Kinase C as a Therapeutic Target in Non-Small Cell Lung Cancer.

Driver-directed therapeutics have revolutionized cancer treatment, presenting similar or better efficacy compared to traditional chemotherapy and substantially improving quality of life. Despite significant advances, targeted therapy is greatly limited by resistance acquisition, which emerges in nearly all patients receiving treatment. As a result, identifying the molecular modulators of resistance is of great interest. Recent work has implicated protein kinase C (PKC) isozymes as mediators of drug resistance in non-small cell lung cancer (NSCLC). Importantly, previous findings on PKC have implicated this family of enzymes in both tumor-promotive and tumor-suppressive biology in various tissues. Here, we review the biological role of PKC isozymes in NSCLC through extensive analysis of cell-line-based studies to better understand the rationale for PKC inhibition. PKC isoforms α, ε, η, ι, ζ upregulation has been reported in lung cancer, and overexpression correlates with worse prognosis in NSCLC patients. Most importantly, PKC isozymes have been established as mediators of resistance to tyrosine kinase inhibitors in NSCLC. Unfortunately, however, PKC-directed therapeutics have yielded unsatisfactory results, likely due to a lack of specific evaluation for PKC. To achieve satisfactory results in clinical trials, predictive biomarkers of PKC activity must be established and screened for prior to patient enrollment. Furthermore, tandem inhibition of PKC and molecular drivers may be a potential therapeutic strategy to prevent the emergence of resistance in NSCLC.

The Impact of Facial Asymmetry on the Surgical Outcome of Crooked Nose: A Case Control Study.

BACKGROUND: Facial asymmetry is considered a reason for patient dissatisfaction with the outcome of rhinoplasty. OBJECTIVES: The aim of this study was to evaluate the impact of facial asymmetry on patient postoperative satisfaction with crooked nose and to investigate the relationship between visual perception of asymmetry and anthropometric measurements. METHODS: In this retrospective study, 61 rhinoplasty patients with crooked noses were assessed. Utilizing frontal view photos, pre- and postoperative nasal deviation angles were calculated. The patients were divided into 2 groups based on the visual presence of facial asymmetry. Moreover, anthropometric characteristics of the face were evaluated utilizing facial soft tissue landmarks. Patient satisfaction with surgery outcomes, including both aesthetic and functional aspects, was assessed employing the Persian version of the Standardized Cosmesis and Health Nasal Outcomes Survey. RESULTS: Based on the observations, 19 (30.2%) and 44 (69.8%) patients had I-type and C-type noses, respectively. In both groups, the deviation angle decreased significantly postoperatively (P < 0.001). Regarding the subjective evaluation of facial asymmetry, 22 (34.9%) and 41 (65.1%) cases had symmetric and asymmetric faces, respectively. Anthropometric measurements were also consistent with visual assessments of asymmetry. Satisfaction scores were significantly higher after surgery in all patients; however, there was no significant difference in the mean aesthetic improvement between symmetric (15.83 ± 2.68) and asymmetric faces (15.23 ± 4.46) (P = 0.531). The power of study was 97.8%. CONCLUSIONS: Rhinoplasty in patients with deviated noses and asymmetric faces may have comparable results with symmetric ones.

Lightweight Fine-Grained Access Control for Wireless Body Area Networks.

Wireless Body Area Network (WBAN) is a highly promising technology enabling health providers to remotely monitor vital parameters of patients via tiny wearable and implantable sensors. In a WBAN, medical data is collected by several tiny sensors and usually transmitted to a server-side (e.g., a cloud service provider) for long-term storage and online/offline processing. However, as the health data includes several sensitive information, providing confidentiality and fine-grained access control is necessary to preserve the privacy of patients. In this paper, we design an attribute-based encryption (ABE) scheme with lightweight encryption and decryption mechanisms. Our scheme enables tiny sensors to encrypt the collected data under an access control policy by performing very few computational operations. Also, the computational overhead on the users in the decryption phase is lightweight, and most of the operations are performed by the cloud server. In comparison with some excellent ABE schemes, our encryption mechanism is more than 100 times faster, and the communication overhead in our scheme decreases significantly. We provide the security definition for the new primitive and prove its security in the standard model and under the hardness assumption of the decisional bilinear Diffie-Hellman (DBDH) problem.