Chromatin regulation of transcriptional enhancers and cell fate by the Sotos syndrome gene NSD1.

Nuclear receptor-binding SET-domain protein 1 (NSD1), a methyltransferase that catalyzes H3K36me2, is essential for mammalian development and is frequently dysregulated in diseases, including Sotos syndrome. Despite the impacts of H3K36me2 on H3K27me3 and DNA methylation, the direct role of NSD1 in transcriptional regulation remains largely unknown. Here, we show that NSD1 and H3K36me2 are enriched at cis-regulatory elements, particularly enhancers. NSD1 enhancer association is conferred by a tandem quadruple PHD (qPHD)-PWWP module, which recognizes p300-catalyzed H3K18ac. By combining acute NSD1 depletion with time-resolved epigenomic and nascent transcriptomic analyses, we demonstrate that NSD1 promotes enhancer-dependent gene transcription by facilitating RNA polymerase II (RNA Pol II) pause release. Notably, NSD1 can act as a transcriptional coactivator independent of its catalytic activity. Moreover, NSD1 enables the activation of developmental transcriptional programs associated with Sotos syndrome pathophysiology and controls embryonic stem cell (ESC) multilineage differentiation. Collectively, we have identified NSD1 as an enhancer-acting transcriptional coactivator that contributes to cell fate transition and Sotos syndrome development.

Rapid and robust directed differentiation of mouse epiblast stem cells into definitive endoderm and forebrain organoids.

Directed differentiation of pluripotent stem cells (PSCs) is a powerful model system for deconstructing embryonic development. Although mice are the most advanced mammalian model system for genetic studies of embryonic development, state-of-the-art protocols for directed differentiation of mouse PSCs into defined lineages require additional steps and generates target cell types with lower purity than analogous protocols for human PSCs, limiting their application as models for mechanistic studies of development. Here, we examine the potential of mouse epiblast stem cells cultured in media containing Wnt pathway inhibitors as a starting point for directed differentiation. As a proof of concept, we focused our efforts on two specific cell/tissue types that have proven difficult to generate efficiently and reproducibly from mouse embryonic stem cells: definitive endoderm and neural organoids. We present new protocols for rapid generation of nearly pure definitive endoderm and forebrain-patterned neural organoids that model the development of prethalamic and hippocampal neurons. These differentiation models present new possibilities for combining mouse genetic tools with in vitro differentiation to characterize molecular and cellular mechanisms of embryonic development.

The HyperPed-COVID international registry: Impact of age of onset, disease presentation and geographical distribution on the final outcome of MIS-C.

OBJECTIVES: The aim of the study was to establish an international multicenter registry to collect data on patients with Multisystem Inflammatory Syndrome in Children (MIS-C), in order to highlight a relationship between clinical presentation, age of onset and geographical distribution on the clinical outcome. STUDY DESIGN: Multicenter retrospective study involving different international societies for rare immunological disorders.1009 patients diagnosed with MIS-C between March and September 2022, from 48 centers and 22 countries were collected. Five age groups (<1, 1-4, 5-11, 12-16, >16 years) and four geographic macro-areas, Western Europe, Central-Eastern Europe, Latin America, Asian-African resource-limited countries (LRC), were identified. RESULTS: Time to referral was significantly higher in LRC. Intensive anti-inflammatory treatment, including biologics, respiratory support and mechanic ventilation were more frequently used in older children and in European countries. The mortality rate was higher in very young children (<1 year), in older patients (>16 years of age) and in LRC. Multivariate analysis identified the residence in LRC, presence of severe cardiac involvement, renal hypertension, lymphopenia and non-use of heparin prophylaxis, as the factors most strongly associated with unfavorable outcomes. CONCLUSIONS: The stratification of patients by age and geographic macro-area provided insights into the clinical presentation, treatment and outcome of MIS-C. The mortality and sequelae rates exhibited a correlation with the age and geographical areas. Patients admitted and treated in LRC displayed more severe outcomes, possibly due to delays in hospital admission and limited access to biologic drugs and to intensive care facilities.

British South Asian ancestry participants views of pharmacogenomics clinical implementation and research: a thematic analysis.

BACKGROUND: South Asian ancestry populations are underrepresented in genomic studies and therapeutics trials. British South Asians suffer from multi-morbidity leading to polypharmacy. Our objective was to elucidate British South Asian ancestry community perspectives on pharmacogenomic implementation and sharing pharmacogenomic clinical data for research. METHODS: Four focus groups were conducted (9-12 participants in each). Two groups were mixed gender, while one group was male only and one was female only. Simultaneous interpretation was available to participants in Urdu and Bengali. Focus groups were recorded and abridged transcription and thematic analysis were undertaken. RESULTS: There were 42 participants, 64% female. 26% were born in the UK or Europe. 52% were born in Bangladesh and 17% in Pakistan. 36% reported university level education. Implementation of pharmacogenomics was perceived to be beneficial to individuals but pose a risk of overburdening resource limited systems. Pharmacogenomic research was perceived to be beneficial to the community, with concerns about data privacy and misuse. Data sharing was desirable if the researchers did not have a financial stake, and benefits would be shared. Trust was the key condition for the acceptability of both clinical implementation and research. Trust was linked with medication compliance. Education, outreach, and communication facilitate trust. CONCLUSIONS (SIGNIFICANCE AND IMPACT OF THE STUDY): Pharmacogenomics implementation with appropriate education and communication has the potential to enhance trust and contribute to increased medication compliance. Trust drives data sharing, which would enable enhanced representation in research. Representation in scientific evidence base could cyclically enhance trust and compliance.

Primary mucosal melanomas of the head and neck are characterised by overexpression of the DNA mutating enzyme APOBEC3B.

AIMS: Primary head/neck mucosal melanomas (MMs) are rare and exhibit aggressive biologic behaviour and elevated mutational loads. The molecular mechanisms responsible for high genomic instability observed in head/neck MMs remain elusive. The DNA cytosine deaminase APOBEC3B (A3B) constitutes a major endogenous source of mutation in human cancer. A3B-related mutations are identified through C-to-T/-G base substitutions in 5'-TCA/T motifs. Herein, we present immunohistochemical and genomic data supportive of a role for A3B in head/neck MMs. METHODS AND RESULTS: A3B protein levels were assessed in oral (n = 13) and sinonasal (n = 13) melanomas, and oral melanocytic nevi (n = 13) by immunohistochemistry using a custom rabbit α-A3B mAb (5210-87-13). Heterogeneous, selective-to-diffuse, nuclear only, A3B immunopositivity was observed in 12 of 13 (92.3%) oral melanomas (H-score range = 9-72, median = 40) and 8 of 13 (62%) sinonasal melanomas (H-score range = 1-110, median = 24). Two cases negative for A3B showed prominent cytoplasmic staining consistent with A3G. A3B protein levels were significantly higher in oral and sinonasal MMs than intraoral melanocytic nevi (P < 0.0001 and P = 0.0022, respectively), which were A3B-negative (H-score range = 1-8, median = 4). A3B levels, however, did not differ significantly between oral and sinonasal tumours (P > 0.99). NGS performed in 10 sinonasal MMs revealed missense NRAS mutations in 50% of the studied cases and one each KIT and HRAS mutations. Publicly available whole-genome sequencing (WGS) data disclosed that the number of C-to-T mutations and APOBEC3 enrichment score were markedly elevated in head/neck MMs (n = 2). CONCLUSION: The above data strongly indicate a possible role for the mutagenic enzyme A3B in head/neck melanomagenesis, but not benign melanocytic neoplasms.

Health outcomes of sensory hypersensitivities in myalgic encephalomyelitis/chronic fatigue syndrome and multiple sclerosis.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a poorly understood chronic illness with many case definitions that disagree on key symptoms, including hypersensitivities to noise and lights. The aim of the current study was to understand the prevalence rates and characteristics of these symptoms amongst people with ME/CFS and to compare them to people with another chronic illness, multiple sclerosis (MS). International datasets consisting of 2,240 people with either ME/CFS or MS have completed the DePaul Symptom Questionnaire (DSQ) and the Short Form Health Survey Questionnaire (SF-36). Hypersensitivities to noise and lights were indicated from items on the DSQ, and participants were analyzed against DSQ and SF-36 subscales through a multivariate analysis of covariance. There were significantly higher percentages of people with hypersensitivities in the ME/CFS sample compared to the MS sample. Regardless of illness, participants that exhibited both hypersensitivities reported greater symptomology than those without hypersensitivities. Healthcare providers and researchers should consider these symptoms when developing treatment plans and evaluating ME/CFS case diagnostic criteria.

Sex hormones regulate metainflammation in diet-induced obesity in mice.

Men have a statistically higher risk of metabolic and cardiovascular disease than premenopausal women, but the mechanisms mediating these differences are elusive. Chronic inflammation during obesity contributes to disease risk and is significantly more robust in males. Prior work demonstrated that compared with obese males, obese females have reduced proinflammatory adipose tissue macrophages (ATMs). Given the paucity of data on how sex hormones contribute to macrophage responses in obesity, we sought to understand the role of sex hormones in promoting obesity-induced myeloid inflammation. We used gonadectomy, estrogen receptor-deficient alpha chimeras, and androgen-insensitive mice to model sex hormone deficiency. These models were evaluated in diet-induced obesity conditions (high-fat diet [HFD]) and in vitro myeloid assays. We found that ovariectomy increased weight gain and adiposity. Ovariectomized females had increased ATMs and bone marrow myeloid colonies compared with sham-gonadectomized females. In addition, castrated males exposed to HFD had improved glucose tolerance, insulin sensitivity, and adiposity with fewer Ly6chi monocytes and bone marrow myeloid colonies compared with sham-gonadectomized males, although local adipose inflammation was enhanced. Similar findings were observed in androgen-insensitive mice; however, these mice had fewer CD11c+ ATMs, implying a developmental role for androgens in myelopoiesis and adipose inflammation. We concluded that gonadectomy results in convergence of metabolic and inflammatory responses to HFD between the sexes, and that myeloid estrogen receptor alpha contributes minimally to diet-induced inflammatory responses, whereas loss of androgen-receptor signaling improves metabolic and inflammatory outcomes. These studies demonstrate that sex hormones play a critical role in sex differences in obesity, metabolic dysfunction, and myeloid inflammation.

Associations of accelerometer measured school- and non-school based physical activity and sedentary time with body mass index: IPEN Adolescent study.

BACKGROUND: This study examined the strength, shape and direction of associations of accelerometer-assessed overall, school- and non-school-based moderate-to-vigorous physical activity (MVPA) and sedentary time (ST) with BMI among adolescents across the world. Second, we examined whether these associations differed by study site and sex. METHODS: Cross-sectional data from the IPEN Adolescent study, an observational multi-country study, were used. Participants wore an accelerometer for seven days, reported height and weight, and completed a socio-demographic survey. In total, 4852 adolescents (46.6% boys), aged 11-19 years (mean age = 14.6, SD = 1.7 years) were included in the analyses, using generalized additive mixed models. RESULTS: Adolescents accumulated on average 41.3 (SD = 22.6) min/day of MVPA and 531.8 (SD = 81.1) min/day of ST, and the prevalence of overweight and obesity was 17.2% (IOTF), but these mean values differed by country. Linear negative associations of accelerometer-based MVPA and ST with standardized BMI scores and the likelihood of being overweight/obese were found. School-based ST and non-school-based MVPA were more strongly negatively associated to the outcomes than non-school based ST and school-based MVPA. Study site moderated the associations; adolescent sex did not. No curvilinear associations were found. CONCLUSIONS: This multi-country study confirmed the importance of MVPA as a potential protective factor against overweight/obesity in adolescents. Non-school-based MVPA seemed to be the main driver of these associations. Unexpected results were found for ST, calling for further examination in methodologically sound international studies but using inclinometers or pressure sensors to provide more precise ST measures.

Explainable Artificial Intelligence Model for Stroke Prediction Using EEG Signal.

State-of-the-art healthcare technologies are incorporating advanced Artificial Intelligence (AI) models, allowing for rapid and easy disease diagnosis. However, most AI models are considered "black boxes," because there is no explanation for the decisions made by these models. Users may find it challenging to comprehend and interpret the results. Explainable AI (XAI) can explain the machine learning (ML) outputs and contribution of features in disease prediction models. Electroencephalography (EEG) is a potential predictive tool for understanding cortical impairment caused by an ischemic stroke and can be utilized for acute stroke prediction, neurologic prognosis, and post-stroke treatment. This study aims to utilize ML models to classify the ischemic stroke group and the healthy control group for acute stroke prediction in active states. Moreover, XAI tools (Eli5 and LIME) were utilized to explain the behavior of the model and determine the significant features that contribute to stroke prediction models. In this work, we studied 48 patients admitted to a hospital with acute ischemic stroke and 75 healthy adults who had no history of identified other neurological illnesses. EEG was obtained within three months following the onset of ischemic stroke symptoms using frontal, central, temporal, and occipital cortical electrodes (Fz, C1, T7, Oz). EEG data were collected in an active state (walking, working, and reading tasks). In the results of the ML approach, the Adaptive Gradient Boosting models showed around 80% accuracy for the classification of the control group and the stroke group. Eli5 and LIME were utilized to explain the behavior of the stroke prediction model and interpret the model locally around the prediction. The Eli5 and LIME interpretable models emphasized the spectral delta and theta features as local contributors to stroke prediction. From the findings of this explainable AI research, it is expected that the stroke-prediction XAI model will help with post-stroke treatment and recovery, as well as help healthcare professionals, make their diagnostic decisions more explainable.

1,5-Benzothiazepine Derivatives: Green Synthesis, In Silico and In Vitro Evaluation as Anticancer Agents.

Considering the importance of benzothiazepine pharmacophore, an attempt was carried out to synthesize novel 1,5-benzothiazepine derivatives using polyethylene glycol-400 (PEG-400)-mediated pathways. Initially, different chalcones were synthesized and then subjected to a cyclization step with benzothiazepine in the presence of bleaching clay and PEG-400. PEG-400-mediated synthesis resulted in a yield of more than 95% in less than an hour of reaction time. Synthesized compounds 2a-2j were investigated for their in vitro cytotoxic activity. Moreover, the same compounds were subjected to systematic in silico screening for the identification of target proteins such as human adenosine kinase, glycogen synthase kinase-3ß, and human mitogen-activated protein kinase 1. The compounds showed promising results in cytotoxicity assays; among the tested compounds, 2c showed the most potent cytotoxic activity in the liver cancer cell line Hep G-2, with an IC50 of 3.29 ± 0.15 µM, whereas the standard drug IC50 was 4.68 ± 0.17 µM. In the prostate cancer cell line DU-145, the compounds displayed IC50 ranges of 15.42 ± 0.16 to 41.34 ± 0.12 µM, while the standard drug had an IC50 of 21.96 ± 0.15 µM. In terms of structural insights, the halogenated phenyl substitution on the second position of benzothiazepine was found to significantly improve the biological activity. This characteristic feature is supported by the binding patterns on the selected target proteins in docking simulations. In this study, 1,5-benzothiazepines have been identified as potential anticancer agents which can be further exploited for the development of more potent derivatives.

Enhancement of Anti-Tumoral Properties of Paclitaxel Nano-Crystals by Conjugation of Folic Acid to Pluronic F127: Formulation Optimization, In Vitro and In Vivo Study.

A brand-new nano-crystal (NC) version of the hydrophobic drug Paclitaxel (PT) were formulated for cancer treatment. A stable NC formulation for the administration of PT was created using the triblock co-polymer Pluronic F127. To achieve maximum entrapment effectiveness and minimal particle size, the formulation was improved using the central composite design by considering agitation speed and vacuum pressure at five levels (coded as +1.414, +1, 0, -1, and -1.414). According to the Design Expert software's predictions, 13 runs were created and evaluated for the chosen responses. The formulation prepared with an agitation speed of 1260 RPM and a vacuum pressure of 77.53 mbar can meet the requirements of the ideal formulation in order to achieve 142.56 nm of PS and 75.18% EE, according to the level of desirability (D = 0.959). Folic acid was conjugated to Pluronic F127 to create folate receptor-targeted NC. The drug release profile of the nano-crystals in vitro demonstrated sustained release over an extended period. Folate receptor (FR)-targeted NC (O-PT-NC-Folate) has also been prepared by conjugating folic acid to Pluronic F127. MTT test is used to validate the targeting efficacy on the FR-positive human oral cancer cell line (KB). At pharmacologically relevant concentrations, the PT nano-crystal formulation did not cause hemolysis. Compared to non-targeted NC of PT, the O-PT-NC-Folate showed a comparable but more sustained anti-cancer effect, according to an in vivo anti-tumor investigation in NCI/ADR-RES cell lines. The remarkable anti-tumor effectiveness, minimal toxicity, and simplicity of scale-up manufacturing of the NC formulations indicate their potential for clinical development. Other hydrophobic medications that are formulated into nano-systems for improved therapy may benefit from the formulation approach.

Social integration in recovery living environments: A dynamic network approach.

Oxford Houses (OHs) are a large network of self-run community-based settings for individuals with substance use disorders. This present study explored a model based on conceptualizing recovery home social systems as dynamic multirelational (multiplex) social networks. The model is developed from data obtained from 42 OH recovery homes in three parts of the US, addressing whole networks of friendship, close friendship, and willingness to loan money. Findings indicated that close friend and loan relationships mutually reinforced each other over time as they coevolved. These types of insights can help community psychologists to better understand complex network dynamics in community-based settings.

Willingness to Lend Resources is Associated with Increases in Recovery and Participation in Community Activities.

Recovery homes may facilitate individuals with substance use disorders re-integration back into community settings by providing friendship, resources, and advice. Participants of the current study were over 600 residents of 42 Oxford House recovery homes. Findings indicated that willingness to share resources in the form of loans was associated with higher levels of house involvement in recovery home chapters. Active involvement in house and community affairs may influence more recovery within homes or may be an indicator of houses with residents with more capacities and skills for positive long-term health outcomes. Such findings suggest that recovery is a dynamic process with multiple ecological layers embedding individuals, their immediate social networks, and the wider community.

Risks for Developing Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in College Students Following Infectious Mononucleosis: A Prospective Cohort Study.

BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) involves severe fatigue, unrefreshing sleep, and cognitive impairment, leading to functional difficulties; prior studies have not evaluated risk factors with behavioral and immune data collected before developing ME/CFS. Up to 5% of university students develop infectious mononucleosis (IM) annually, and 9-12% meet criteria for ME/CFS 6 months later. We sought to determine predictors of ME/CFS. METHODS: We enrolled college students at the start of the school year (time 1), identified those who developed IM (time 2), and followed them for 6 months (time 3), identifying 3 groups: those who developed ME/CFS, severe ME/CFS (meeting >1 set of criteria), and who were asymptomatic. We conducted 8 behavioral and psychological surveys and analyzed cytokines at 3 time points. RESULTS: 238 of the 4501 students (5.3%) developed IM; 6 months later, 55 of the 238 (23%) met criteria for ME/CFS and 157 (66%) were asymptomatic. 67 of the 157 asymptomatic students served as controls. Students with severe ME/CFS were compared with students who were asymptomatic at 3 time points. The former group was not different from the latter group at time 1 (prior to developing IM) in stress, coping, anxiety, or depression but were different in several behavioral measures and had significantly lower levels of IL-6 and IL-13. At time 2 (when they developed IM), the 2 ME/CFS groups tended to have more autonomic complaints and behavioral symptoms while the severe-ME/CFS group had higher levels of IL-12 and lower levels of IL-13 than the recovered group. CONCLUSIONS: At baseline, those who developed ME/CFS had more physical symptoms and immune irregularities, but not more psychological symptoms, than those who recovered.

Squamous Odontogenic Tumor: Review of the Literature and Report of a New Case.

PURPOSE: Squamous odontogenic tumor (SOT) is a rare, benign, locally infiltrative odontogenic tumor of the gnathic bones. It is composed of islands of bland, well-differentiated squamous epithelium of varying shape and size. Because of histologic overlap, SOT has often been overdiagnosed as ameloblastoma and squamous cell carcinoma. It thus becomes important to understand the clinical, radiologic, histopathologic, and treatment characteristics of this tumor. MATERIALS AND METHODS: Using the PubMed and Google Scholar databases, we searched for reported cases of SOT published in the English-language literature. We were able to retrieve 49 acceptable cases and perform a comprehensive literature review of the intraosseous SOTs, with emphasis on their clinical, radiographic, and pathologic characteristics, as well as treatment strategies. In addition, we present an additional case of SOT affecting the posterior mandible in a 44-year-old female patient. RESULTS: The tumor in the posterior mandible in our patient was accompanied by acute pain and treated by enucleation. Histopathologic evaluation showed variably sized islands of benign squamous epithelium scattered in a fibrous stroma, consistent with the diagnosis of an SOT. Uneventful healing was noted at the 1-month postoperative appointment. However, the patient was lost to long-term follow-up. Our literature review showed that the average age at the time of diagnosis of SOT is 34.2 years. Men and women are equally affected, and the tumor does not show a predilection for either jaw bone. The most common locations are the anterior maxilla and posterior mandible. Most SOTs are treated conservatively by enucleation or curettage, whereas aggressive or recurrent tumors require radical resection. CONCLUSIONS: Careful evaluation of the excised specimen, with immunohistochemical investigations, may prove rewarding in differentiating an SOT from other odontogenic neoplasms and thus minimize the patient's chances of undergoing an unnecessary aggressive intervention.

Revisiting the plant growth-promoting rhizobacteria: lessons from the past and objectives for the future.

Plant beneficial rhizobacteria (PBR) is a group of naturally occurring rhizospheric microbes that enhance nutrient availability and induce biotic and abiotic stress tolerance through a wide array of mechanisms to enhance agricultural sustainability. Application of PBR has the potential to reduce worldwide requirement of agricultural chemicals and improve agro-ecological sustainability. The PBR exert their beneficial effects in three major ways; (1) fix atmospheric nitrogen and synthesize specific compounds to promote plant growth, (2) solubilize essential mineral nutrients in soils for plant uptake, and (3) produce antimicrobial substances and induce systemic resistance in host plants to protect them from biotic and abiotic stresses. Application of PBR as suitable inoculants appears to be a viable alternative technology to synthetic fertilizers and pesticides. Furthermore, PBR enhance nutrient and water use efficiency, influence dynamics of mineral recycling, and tolerance of plants to other environmental stresses by improving health of soils. This report provides comprehensive reviews and discusses beneficial effects of PBR on plant and soil health. Considering their multitude of functions to improve plant and soil health, we propose to call the plant growth-promoting bacteria (PGPR) as PBR.

p16INK4a as a proliferation marker unrelated to HPV expression in odontogenic cysts and tumors.

INTRODUCTION: p16INK4a is a tumor suppressor protein that retards cell cycle progression from G1 to S phase. Prior studies have evaluated p16INK4a expression in odontogenic keratocyst and ameloblastoma, but data regarding other odontogenic cysts and tumors have been sparse. METHODS: With IRB approval, cases from the following entities were identified from archives of the UF Oral Pathology Biopsy Service (2005-2015): benign incidental odontogenic rest, dentigerous cyst, lateral periodontal cyst, calcifying odontogenic cyst, glandular odontogenic cyst, odontogenic keratocyst, orthokeratinized odontogenic cyst, adenomatoid odontogenic tumor, calcifying epithelial odontogenic tumor, and ameloblastoma. All cases were submitted for p16INK4a immunohistochemical testing. RESULTS: Results were scored as follows: nuclear and cytoplasmic staining of <5% cells (score 0), 5%-25% (score 1), 25%-50% (score 2), >50% (score 3). No significant difference in p16INK4a staining was noted between odontogenic cysts and the listed odontogenic tumors (chi-square, P = .540). When comparing lesions with higher recurrence rates (over 25% as reported in the literature) versus lesions with low recurrence rates (under 25%), higher recurrence correlated to significantly higher p16INK4a positivity (chi-square, P = .001). Follow-up testing was performed on 18 cases with "2" or "3" p16INK4a expression scores for high-risk HPV strains through HPV in situ hybridization (ISH) messenger RNA testing with no cases exhibiting a positive result. CONCLUSION: This study exhibits an association between increased p16INK4a positivity and odontogenic lesions with higher recurrence rates and highlights the role of p16INK4a as a progression marker unrelated to HPV expression in this group of pathologic entities.

Elective neck dissection in T1/T2 oral squamous cell carcinoma with N0 neck: essential or not? A systematic review and meta-analysis.

INTRODUCTION: Oral squamous cell carcinoma (SCC) is characterized by a high risk of cervical lymph node metastasis with a high incidence of occult metastasis. A strong debate is still present regarding the best treatment for early oral cavity cancer with N0 neck. OBJECTIVE: The aim of the present study was to compare between the results of elective neck dissection (END) and watchful waiting (observation or therapeutic neck dissection) in patients with early-stage (T1/T2) oral squamous cell carcinoma with N0 neck. DATA SOURCES: Medline database (https://www.pubmed.com), Google Scholar and Scopus. PATIENTS AND METHODS: A systematic review and meta-analysis for the evaluation of regional recurrence rate and 5-year survival rate after elective neck dissection (END) or watchful waiting in early oral cancers were conducted. This study included published English medical articles (which met our predetermined inclusion criteria) in the last 30 years, concerning early oral SCC with N0 neck. 24 articles were included (4 randomized studies and 20 observational "retrospective" studies) with a total number of 2190 of patients who underwent END and 1619 who underwent watchful waiting. Regarding the 5-year survival rate, (10) studies were included with a total number of 1211 patients who underwent END and 948 who underwent watchful waiting. RESULTS: Regarding the regional recurrence rate, (END) was associated with significantly lower risk of recurrence when compared with observation. Regarding the 5-year survival rate, END was associated with a better survival rate than the observational group. CONCLUSIONS: Elective neck dissection is better than watchful waiting in early (T1/T2) stage oral cavity squamous cell carcinoma with N0 neck, regarding regional recurrence and 5-year survival rate.

Regressive models for risk prediction of repeated multinomial outcomes: An illustration using Health and Retirement Study data.

Life expectancy is increasing in many countries and this may lead to a higher frequency of adverse health outcomes. Therefore, there is a growing demand for predicting the risk of a sequence of events based on specified factors from repeated outcomes. We proposed regressive models and a framework to predict the joint probabilities of a sequence of events for multinomial outcomes from longitudinal studies. The Markov chain is used to link marginal and sequence of conditional probabilities to predict the joint probability. Marginal and sequence of conditional probabilities are estimated using marginal and regressive models. An application is shown using the Health and Retirement Study data. The bias of parameter estimates for all models from all bootstrap simulation is less than 1% in most of the cases. The estimated mean squared error is also very low. Results from the simulation study show negligible bias and the usefulness of the proposed model. The proposed model and framework would be useful to solve real-life problems from various fields and big data analysis.

A Novel Multiplex RT-PCR Assay for Simultaneous Detection of Dengue and Chikungunya Viruses.

The goal of the study was to develop a specific, sensitive, and cost-effective molecular RT-PCR diagnostic assay for the rapid and simultaneous detection of the serotypes of dengue virus (DENV) and Chikungunya virus (CHIKV) from sera of suspected febrile patients. A single-tube, single-step multiplex RT-PCR (mRT-PCR) assay was designed for the detection of viral genomes from clinical and field samples. Specificity and sensitivity of the mRT-PCR assay were evaluated against six different combinations using two reverse transcriptases (AMV-RT and RT-Ace) and three DNA polymerases (LA-Taq, rTaq, and Tth). Among the six combinations, the AMV-RT and LA-Taq combination was more specific and sensitive than other enzyme combinations for detecting viral genomes of DENV-1, DENV-2, DENV-3, and DENV-4 (p < 0.01), and for detecting viral genomes of CHIKV (p < 0.05). The detection limits of the mRT-PCR were 10 focus forming units (FFU) for CHIKV and 1 FFU, 20 FFU, 0.1 FFU, and 10 FFU for DENV-1, DENV-2, DENV-3, and DENV-4, respectively. The primers used for the mRT-PCR did not show any cross-reactivity among the serotypes of DENV or CHIKV. Specificity and sensitivity of the newly developed mRT-PCR were validated using serum samples collected from febrile patients during dengue outbreaks in Bangladesh. The sensitivity for serotype detection of DENV and CHIKV was superior to the virus isolation method and the antigen detection method using the Dengue NS1-Ag assay. This novel mRT-PCR method can be used for molecular epidemiological surveillance of DENV and CHIKV in epidemic and endemic countries.