Identification of hub genes associated with head and neck squamous cell carcinoma by integrated bioinformatics approach and RNA-seq validation analysis.

Head and neck squamous cell carcinoma (HNSC) is one of the most lethal malignancies around the globe. Due to its complex nature, the diagnostic and prognostic signatures of HNSC remain poorly understood. This study was launched to identify signature genes and their signaling pathways related to the development of HNSC. In the current study, we retrieved the GSE53819 dataset from the Gene Expression Omnibus (GEO) database to determine the differentially expressed genes (DEGs) using the "Limma" R package. Adjusted P values P < 0.05 and |logFC| ≥ 1 were selected as the filtering conditions. To identify hub genes, the protein-protein interaction (PPI) network construction of the DEGs was performed using STRING. We further used UALCAN, GEPIA, OncoDB, GENT2, MEXPRESS, and HPA databases for the expression, validation, survival, and methylation analyses of the hub genes. The cBioPortal tool was used to investigate the genetic alterations in hub genes. CancerSEA, TIMER, DAVID, ENCORI, and DrugBank were also used to explore a few more hub gene-associated parameters. Lastly, HOK, FaDu, and SCC25 cell lines were used to validate hub gene expression via RNA sequencing (RNA-seq) technique. A total of top 250 DEGs were selected for detailed analysis in this study. From these DEGs, prognostic and diagnostic associated four hub genes, which could serve as potential molecular biomarkers and therapeutic targets in HNSC patients were identified. Four hub genes, including down-regulated DNAH1 and DNALI1, while up-regulated DNAH9 and CCDC151 were strongly implicated in HNSC. We also validated the same expression pattern of the hub genes using RNA-seq analysis in HNSC and normal cell lines. Moreover, this study also revealed some novel links between DNAH1, DNALI1, DNAH9, and CCDC151 expression and genetic alterations, promoter methylation status, immune cell infiltration, miRNAs, gene enrichment terms, and various chemotherapeutic drugs. In conclusion, we indicated four hub genes (DNAH1, DNALI1, DNAH9, and CCDC151) and their associated signaling pathways, which may improve our understanding of HNSC and could be used as new therapeutic targets.

Adherence to Clinical Practice Guideline Recommendations in Women with Gestational Diabetes and Associations with Maternal and Infant Health-A Cohort Study.

Gestational diabetes mellitus (GDM) is managed by dietary advice, but limited evidence exists about the impact of adherence on health. We assessed whether adherence to the New Zealand Ministry of Health dietary recommendations is associated with maternal and infant health in women with GDM. Data from 313 women with GDM were used. Adherence to food-related recommendations was scored from 0 (no adherence) to 10 (adhered to all recommendations) and analysed in tertile groups (high, moderate, low adherence). Adherence to visiting a dietitian and appropriate weight gain were assessed as yes or no. Chi-square, ANOVA, and odds ratios were used to compare groups. High dietary adherence compared to low adherence was associated with reduced oral hypoglycaemic and insulin use (OR = 0.55, CI = 0.30-1.00). Visiting a dietitian compared to not was associated with increased oral hypoglycaemic and insulin use (OR = 2.96, CI = 1.12-7.80), decreased odds of a large-for-gestational-age infant (OR = 0.32, CI = 0.14-0.73) and neonatal hyperbilirubinaemia (OR = 0.27, CI = 0.08-0.95). Greater than recommended compared with recommended weight gain was associated with increased oral hypoglycaemic and insulin use (OR = 2.51, CI = 1.26-5.01), while lower than recommended weight gain was associated with decreased postpartum haemorrhage (OR = 0.45, CI = 0.23-0.91) and increased breastfeeding (OR = 1.96, CI = 1.04-3.70). Adherence to dietary recommendations for women with GDM likely improves health outcomes.

Sociodemographic Factors Associated with Adherence to Dietary Guidelines in Women with Gestational Diabetes: A Cohort Study.

Dietary advice is the cornerstone of care for women with gestational diabetes mellitus (GDM). However, adherence to this advice is variable. We aimed to identify the proportion of women with GDM who adhere to the New Zealand nutrition guideline recommendations and assess the sociodemographic factors linked to dietary adherence. We assessed dietary intake at 36 weeks' gestation in a cohort of 313 women with GDM and compared this with the dietary recommendations for the management of GDM. Associations between maternal characteristics and dietary adherence were assessed using ANOVA, chi square, logistic regression, and linear regression tests. Women with GDM had an average adherence score of 6.17 out of 10 to dietary recommendations, but no one adhered to all the recommendations. Adherence to recommendations was lowest for saturated fat, and wholegrain breads and cereals. While 85% visited a dietitian, only 28% of women achieved their recommended weight gain. Maternal factors associated with lower dietary adherence were primiparity, no previous history of GDM, being underweight, and smoking. Adherence to the dietary recommendations by women with GDM in New Zealand for the management could be improved. Further research is needed to identify ways for women with GDM to improve their dietary adherence.

Dietary recommendations for women with gestational diabetes mellitus: a systematic review of clinical practice guidelines.

CONTEXT: Dietary advice is the cornerstone of care for women with gestational diabetes mellitus (GDM) to improve maternal and infant health. OBJECTIVES: This study aimed to compare dietary recommendations made in clinical practice guidelines (CPGs) for the management of GDM, evaluate their evidence base, identify research gaps, and assess CPG quality. The PRISMA guidelines were used. DATA SOURCES: Six databases were searched for CPGs, published between 2000 and 2019, that included dietary advice for the management of GDM. DATA EXTRACTION: Two reviewers independently assessed CPG quality (using the AGREE II tool) with respect to dietary recommendations (their strength, evidence base, and research gaps). DATA ANALYSIS: Of the 31 CPGs, 68% were assessed as low quality, mainly due to lack of editorial independence. Dietary advice was recommended as the first-line treatment by all CPGs, although the dietary recommendations themselves varied and sometimes were contradictory. Most dietary recommendations were strongly made (70%), but they were often based on very low-quality (54%), or low-quality (15%) evidence. Research gaps were identified for all diet-related recommendations. CONCLUSION: High-quality research is needed to improve the evidence base and address the research gaps identified. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42019147848.

Acinar cell carcinoma of the pancreas: a clinicopathologic and cytomorphologic review.

Acinar cell carcinoma (ACC) is a rare malignancy of the pancreas with unique clinical, molecular, and morphologic characteristics. Clinically, these cancers can present with hypersecretory syndrome caused by the release of lipase into the circulation. Surgical resection is the treatment of choice for patients with organ-confined disease; however, with recent advances in precision medicine, therapies targeting the distinct molecular profile of ACC are on the horizon. Cytomorphologic features of ACC have been well described in the literature; and in conjunction with available clinical data and appropriate ancillary studies, an accurate diagnosis can be rendered in most instances. The aim of the current article is to present a comprehensive review of ACC based on available literature while attempting to shed light on some of its key histologic and cytologic characteristics.

Cytomorphologic findings of low-grade fibromyxoid sarcoma.

INTRODUCTION: Low-grade fibromyxoid sarcoma (LGFMS) is a rare fibroblastic tumor characterized by a prolonged clinical course and malignant biological behavior. Given its deceptively bland cytomorphology, a diagnosis can be quite challenging notably on fine-needle aspiration (FNA). In an attempt to shed light on some of the distinctive cytomorphologic characteristics, this study was conducted to review all cases of LGFMS in our database, correlating available clinical data, immunohistochemical findings, and molecular analysis. MATERIALS AND METHODS: This series included 20 FNAs from 18 patients with a histologically confirmed LGFMS diagnosis from 3 large academic institutions. Detailed cytomorphologic analysis for each case was documented in conjunction with corresponding clinical characteristics and provided ancillary testing. RESULTS: Out of 14 adequate FNA samples, 9 (64.2%) demonstrated a mixture of fibrous and myxoid pattern; the majority of cases were composed of deceptively bland tumor cells with rare nuclear pleomorphism and nuclear membrane irregularities. A MUC4 immunostain was performed on 5 specimens; all tested positive (100%). FUS rearrangement was detected in 4 out of 5 cases (80%). Follow-up information revealed 5-year recurrence in 1 case and metastatic disease in 2 cases, to the lung/pleura (8 years) and fourth rib (1 year), respectively. CONCLUSIONS: The presence of bland spindle cells and associated with myxoid matrix material, in the appropriate clinical setting, can suggest LGFMS and direct additional confirmatory testing. A definitive diagnosis of LGFMS on FNA requires adequate sampling, familiarity with key cytomorphologic features, acquisition of diagnostic material for a cell block preparation and ancillary testing, and clinicoradiologic correlation.

Impact of the Current US Preventive Services Task Force Recommendations for Cervical Cancer Screening in Young Women 21 to 29 Years Old.

OBJECTIVES: In 2012, the US Preventive Services Task Force decreased the recommended frequency of cervical cytology screening to once every 3 years and recommended against testing women younger than 21 years regardless of sexual history. We evaluated the impact of this in 21 to 29-year-old women at a tertiary care academic medical center in 2011 and 2017. METHODS: We retrospectively analyzed Papanicolaou test results at two time points in 21- to 29-year-old women. RESULTS: There was a decrease in the number of high-grade lesions in 21- to 25-year-old women (odds ratio [OR], 0.36) from 2011 to 2017. Within the 26- to 29-year-old patient group, there was a trend toward a higher percentage of high-grade squamous intraepithelial lesion (HSIL) in 2017 compared to 2011 on cytology, which did not reach statistical significance (OR, 1.46). However, follow-up histologic specimens showed a higher percentage of HSIL in 2017 compared to 2011 in this age group (OR, 2.16). CONCLUSIONS: Our findings suggest that the cervical cancer screening guidelines introduced in 2012 have not had a detrimental impact on the outcomes of cervical cancer screening for 21- to 25-year-old women. However, we need to continue monitoring the effects of decreased screening in 26- to 29-year-old women.

Cytopathologic characteristics of HPV-related small cell carcinoma of the oropharynx.

BACKGROUND: Human papillomavirus (HPV)-related squamous cell carcinoma (SqCC) of the oropharynx is an epidemiologically and clinically distinct form of SqCC that is associated with an improved prognosis. However, HPV-related small cell carcinoma of the oropharynx is a rare and newly described variant that is associated with aggressive clinical behavior and poor outcomes. To date, fewer than 2 dozen reports of this entity exist in the literature, and there is no discussion of cytopathologic features. This article reports 6 cases and discusses the salient cytomorphologic findings, ancillary studies, and challenges when this entity is encountered. METHODS: Anatomic pathology archives were searched to identify patients with a diagnosis of HPV-related small cell carcinoma of the oropharynx. Medical records were reviewed to document the following: age, sex, smoking status, other relevant clinical history, primary location, treatment, and clinical outcome. Both p16 and high-risk HPV in situ hybridization (ISH) studies were positive in at least 1 specimen from each patient. The pathologic diagnoses, cytomorphologic characteristics, immunocytochemical stains, and HPV ISH studies were reviewed and recorded for all available cases. RESULTS: Six patients with 11 cytopathology specimens of HPV-related small cell carcinoma of the oropharynx were identified. The mean age was 61.3 years, and all patients died with widely metastatic disease (mean, 23 months; range, 12-48 months). Mixed small cell carcinoma and SqCC components were present in half of the cases. CONCLUSIONS: The identification of a small cell component can be reliably performed with cytology preparations and is crucial because this (and not the HPV status) determines the prognosis.

Hypertension in Egypt: a systematic review.

BACKGROUND: With 29% of the world's adult population projected to have hypertension by the year 2025, prevention and management of hypertension have become a public health priority. Hypertension also referred to as high blood pressure, in which the arteries have persistent high blood pressure. This results in a condition where the heart has to work harder than normal to flow blood through the vessels. A few years ago, there was no sufficient information about the epidemiology of hypertension, treatment protocols and its consequences in Egypt. Lately, there has been a major change in health system in Egypt, including research development. OBJECTIVES: To evaluate the existing data on prevalence, levels of awareness, treatment and control of hypertension in Egypt with a view of suggestive actions that could enhance control of hypertension and improve quality of life of the patients. METHODS: Six databases (Pub Med, Cochrane, MEDLINE, Sciencedirect, MedEase, Embase) were searched in November 2013, applying the following criteria: published from January 1995 to November 2013 written in English and carried out on human subjects. RESULTS: 21 studies were included in the systematic review of the prevalence, awareness, and control of hypertension in Egypt. The sample size ranged from 27 subjects to 12008 subjects, and the age range from 6-95 years. Every study had both male and female representatives. In most of the studies, the women were more than the men. CONCLUSION: There are declines in the levels of awareness of hypertension and even lower levels of control. Research is required to reveal reasons behind these near to the ground levels of control and treatment, and especially awareness, in order to put in the picture policy for the improvement of quality of life of hypertensive patients in Egypt.

Compliance with pharmacological treatment among patients after minimally invasive coronary bypass grafting.

BACKGROUND: We sought to evaluate patients' adherence to optimal pharmacotherapy as recommendedby the European Society of Cardiology, together with the assessment of potential clinical determinants of medical non-compliance in a large cohort of patients after endoscopic atraumatic coronary artery bypassing (EACAB). METHODS: This cross sectional study was conducted in a group of 706 individuals who underwent EACAB between April 1998 and December 2010. Data covering current pharmacological treatment with antiplatelet agents, beta-blockers (BB) (or heart rate lowering calcium channel blockers [CCB] in case of intolerance and/or poor efficacy of beta-blockade), angiotensin-converting enzyme (ACE) inhibitors (or angiotensin receptor blockers [ARB]) and statins was acquired. Mean duration of observation after the surgery was 2132 ± 1313 days. RESULTS: Complete follow-up data has been obtained from 415 living patients (341 males). Amongst them, 353 (85%) received antiplatelet agents, while BB or CCB were routinely ingested by 349 (84%) patients. Statins were used by 310 (74.7%) individuals and 274 (66%) subjects took ACE inhibitors or ARB. Baseline demographic and clinical features, including major co-morbidities had no impact on patients' compliance with all investigated medications. There was no clear association between adherence to treatment and risk of rehospitalization or occurrence of major cerebral and cardiovascular events. CONCLUSIONS: EACAB patients' compliance with pharmacotherapy guidelines is insufficient and is unrelated to demographic and clinical features of the subjects. Multidisciplinary approach involving health education, enhancement in prescription drug affordability and a better rapport between doctors and patients should be incorporated into clinical practice to overcome therapeutic disobedience.

Quality of life in patients after minimally invasive endoscopic atraumatic coronary artery bypass grafting: a long-term follow-up.

BACKGROUND: Quality of life (QoL) is an acknowledged parameter that subjectively describes treatment effectiveness and is used also in cardiac surgery. Minimally-invasive totally endoscopic atraumatic coronary artery bypass grafting (EACAB) does not require the use of cardiopulmonary bypass, reduces hospital stay and facilitates early rehabilitation. Therefore, this procedure should significantly improve QoL in patients with coronary artery disease. AIM: To assess QoL during a 12-year follow-up in patients who underwent EACAB. METHODS: The study group comprised 706 consecutive patients who underwent EACAB between April 1998 and December 2010. Median duration of follow-up was 1918 days. QoL was assessed by either telephone interview or letter correspondence. Complete data were obtained from 413 persons aged 59 ± 6 years. We evaluated the effect of pre- and postoperative variables on QoL. RESULTS: Compared with the preoperative period, a marked improvement in QoL after EACAB was reported by 38.6%, and improvement by 37.2% of patients. No change in QoL was noted by 18.8% of subjects, and 5.4% of responders reported deterioration of QoL. The following parameters were found to have no impact on QoL: gender (p = 0.3), myocardial infarction (MI) before EACAB (p = 0.3), diabetes mellitus (p = 0.7), and baseline angina severity by the Canadian Cardiovascular Society (CCS) classification (p = 0.8). Time delay between the surgery and QoL assessment had no impact on the results. During the follow-up, reported QoL was related to the severity of angina symptoms (p = 0.006), need for rehospitalisation (p = 0.02), MI (p = 0.04) and repeated revascularisation (p = 0.02). In multivariate analysis, only MI had a significant impact on QoL (p = 0.04). Current drug therapy had no impact on QoL. CONCLUSIONS: EACAB significantly improved QoL in coronary patients. MI during follow-up was associated with deterioration of QoL.

Do malaria preventive interventions reach the poor? Socioeconomic inequities in expenditure on and use of mosquito control tools in Sudan.

OBJECTIVES: To determine levels of socioeconomic inequities in the prevention of malaria, and to examine the implications of the findings for improving the equitable control of malaria in the Sudan. METHODS: A cross-sectional survey using a pre-tested interviewer-administered questionnaire was administered to 720 randomly selected householders from six localities in Gezira and Khartoum States. A socioeconomic status (SES) index, which was developed using principal components analysis, was used to examine socioeconomic inequity in the prevention of malaria. FINDINGS: Socioeconomic status was positively related to expenditures and use of vector control tools. The poorest households spent the least amounts of money to prevent malaria and were the least likely to own mosquito nets. CONCLUSION: The inequity in the prevention of malaria in the study areas has to be redressed before malaria can be effectively controlled in Sudan. Malaria control managers should continually determine the extent to which malaria preventive tools reach the poorest socioeconomic groups, and fashion strategies that will ensure that equity is always maintained.

Socio-economic inequity in demand for insecticide-treated nets, in-door residual house spraying, larviciding and fogging in Sudan.

BACKGROUND: In order to optimally prioritize and use public and private budgets for equitable malaria vector control, there is a need to determine the level and determinants of consumer demand for different vector control tools. OBJECTIVES: To determine the demand from people of different socio-economic groups for indoor residual house-spraying (IRHS), insecticide-treated nets (ITNs), larviciding with chemicals (LWC), and space spraying/fogging (SS) and the disease control implications of the result. METHODS: Ratings and levels of willingness-to-pay (WTP) for the vector control tools were determined using a random cross-sectional sample of 720 householdes drawn from two states. WTP was elicited using the bidding game. An asset-based socio-economic status (SES) index was used to explore whether WTP was related to SES of the respondents. RESULTS: IRHS received the highest proportion of highest preferred rating (41.0%) followed by ITNs (23.1%). However, ITNs had the highest mean WTP followed by IRHS, while LWC had the least. The regression analysis showed that SES was positively and statistically significantly related to WTP across the four vector control tools and that the respondents' rating of IRHS and ITNs significantly explained their levels of WTP for the two tools. CONCLUSION: People were willing to pay for all the vector-control tools, but the demand for the vector control tools was related to the SES of the respondents. Hence, it is vital that there are public policies and financing mechanisms to ensure equitable provision and utilisation of vector control tools, as well as protecting the poor from cost-sharing arrangements.