Homogeneous Population Research Articles

The Clinicopathological Significance of Tumor Cell Subtyping in Appendiceal Neuroendocrine Tumors: A Series of 135 Tumors

Appendiceal neuroendocrine tumors (NETs) are common and often are identified as incidental lesions at the time of appendectomy. The guidelines for management are based on tumor size, degree of invasion, and the Ki67 proliferation index. Most small bowel NETs are composed of serotonin-producing EC-cells, but there are multiple other neuroendocrine cell types. In the rectum, there are L-cell tumors that express peptide YY (PYY), glucagon-like peptides (GLPs), and pancreatic polypeptide (PP); they are thought to have a better prognosis than serotonin-producing tumors. We investigated whether the appendix has distinct neuroendocrine tumor types based on cell type and whether that distinction has clinical significance. We collected 135 appendiceal NETs from the pathology archives of UHN Toronto and UHCMC (Cleveland). We analyzed the expression of biomarkers including CDX2, SATB2, PSAP, serotonin, glucagon (that detects GLPs), PYY, and pancreatic polypeptide (PP) and correlated the results with clinicopathologic parameters. Immunohistochemistry identified three types of appendiceal NETs. There were 75 (56%) classified as EC-cell tumors and 37 (27%) classified as L-cell tumors; the remaining 23 (17%) expressed serotonin and one of the L-cell biomarkers and were classified as mixed. EC-cell tumors were significantly larger with more extensive invasion involving the muscularis propria, subserosa, and mesoappendix compared with L-cell tumors. Mixed tumors were intermediate in all of these parameters. Both EC-cell and mixed tumors had lymphatic and/or vascular invasion while L-cell tumors had none. Unlike EC-cell NETs, L-cell tumors were not associated with lymph node metastasis. Tumor type correlated with pT stage and the only patient with distant metastatic disease in this series had an EC-cell tumor. Our study confirms that appendiceal NETs are not a homogeneous tumor population. There are at least three types of appendiceal NET, including EC-cell, L-cell, and mixed tumors. This information is important for surveillance of patients, as monitoring urinary 5HIAA levels is only appropriate for patients with serotonin-producing tumors, whereas measurement of GLPs and/or PP is more appropriate for patients with L-cell tumors. Our data also show that tumor type is of significance with EC-cell tumors exhibiting the most aggressive behavior.

Curse or a Blessing: Excessive Use of ChatGPT in Academia

This research study provides a comprehensive analysis of excessive use of ChatGPT in academia which started a debate that either the excessive use of ChatGPT in academia is a blessing or a curse. Recently, the advent of artificial intelligence (AI) like ChatGPT had dramatically enhanced the human and computer interaction by offering the unparalleled accessibility and convenience. The study has measured the potential factors of academia which caused the excessive use of ChatGPT. Instant gratification (IG), academia work overload (AW) and social isolation (SI) has been taken as the predictors of excessive use of ChatGPT in academia. By employing the Uses and Gratification theory, it has been observed that how university students seek the help of AI for gratification, to minimize their work load and to mitigate the impact of social isolation. To escape from hard work, to reduce the life stressor and to gain comfort, students constantly seek for positive reinforcement from their tutors. So, positive reinforcement (PR) has been taken as a mediator in the relationship between IG, AW, SI and excessive use of ChatGPT. Access and technical know-how will strengthen the relationship of IG, AW, SI and PR while lack of technological literacy will lessen the strength of such relationship. Hence, technological literacy (TL) has been taken a moderator for IG, AW, SI and PR. Data has been collected from a homogenous population of business and management students of public and private universities of southern Punjab, Pakistan. A survey has been by conducted by distributing a structured questionnaire to 1100 graduate and undergraduate students. Out of which 678 students responded. At the end 617 useable responses were recorded for analysis. It has been found that IG, AW and SI enhances the use of ChatGPT while PR partially moderates this relationship. Additionally, TL strengths the relationship of IG, AW, SI and PR. The study measured the possible reasons of excessive use of ChatGPT in the academia while the perils of AI is yet to be explored in academia.

The Influence Of The Drill Method On Futsal Passing Technique Skills Using The Inside Of The Foot

The purpose of this paper is to measure futsal passing skills using the drill method on a wall target. In group division, they were divided into two groups with 13 experimental students and 12 play method students. The result data obtained from the pre-test contained 3 (23%) students with adequate assessment criteria, and 10 (77%) students with inadequate assessment criteria. The increase occurred after being given the drilling method treatment on the wall target, and data obtained from post-test observations showed that there were 8 (61.5%) students who achieved the adequate assessment criteria and 5 (38.5%) students who achieved the good assessment criteria. The results of the normality test in the experimental group show that Ho is accepted, because calculated X2 X2 table. And the Homogeneity Test proves F count F table, so it can be said that the population is a homogeneous population. This research was said to be successful because students experienced progress as a result of applying the drill method treatment to the wall target.

One-Step Purification and N-Terminal Functionalization of Bioactive Proteins via Atypically Split Inteins.

Site-specific installation of non-natural functionality onto proteins has enabled countless applications in biotechnology, chemical biology, and biomaterials science. Though the N-terminus is an attractive derivatization location, prior methodologies targeting this site have suffered from low selectivity, a limited selection of potential chemical modifications, and/or challenges associated with divergent protein purification/modification steps. In this work, we harness the atypically split VidaL intein to simultaneously N-functionalize and purify homogeneous protein populations in a single step. Our method─referred to as VidaL-tagged expression and protein ligation (VEPL)─enables modular and scalable production of N-terminally modified proteins with native bioactivity. Demonstrating its flexibility and ease of use, we employ VEPL to combinatorially install 4 distinct (multi)functional handles (e.g., biotin, alkyne, fluorophores) to the N-terminus of 4 proteins that span three different classes: fluorescent (Enhanced Green Fluorescent Protein, mCherry), enzymatic (β-lactamase), and growth factor (epidermal growth factor). Moving forward, we anticipate that VEPL's ability to rapidly generate and isolate N-modified proteins will prove useful across the growing fields of applied chemical biology.

Long-Term Neurodevelopmental Outcomes in Children with Gastroschisis: A Review of the Literature.

This study aimed to investigate and present a review of the literature on long-term neurodevelopmental outcomes in children with gastroschisis. Gastroschisis is the most common abdominal wall defect. Children with gastroschisis are at high risk for premature birth, intestinal failure, sepsis, and repeated anesthesia exposure, which collectively increase the risk for adverse long-term neurodevelopmental outcomes. The existing literature on neurodevelopmental outcomes is limited in number, quality, and generalizability, creating a gap in clinical knowledge and care. Five internet databases were searched by a professional research librarian: Ovid MEDLINE, Scopus, Web of Science, PsycINFO, and Cochrane Library. Included articles were (1) published in English, (2) included postneonatal hospital discharge neurodevelopmental outcomes of children with gastroschisis, and (3) included patients under the age of 18 years. No date parameters were applied. The paucity of literature on long-term neurodevelopmental outcomes in gastroschisis children has left large gaps in the body of knowledge on post-hospital care of such children. In this review, 37 articles were found evaluating neurodevelopmental outcomes in gastroschisis and, while conclusions were contradictory, the literature broadly indicated the potential for neurodevelopmental deficits in the gastroschisis pediatric population. A significant limitation of this review was the heterogeneous samples included in available literature, which confounded the ability to determine cognitive risk of gastroschisis independent of other abdominal wall defects. Findings of this review demonstrate potential risk for neurodevelopmental deficits in the pediatric gastroschisis population exist, yet additional research is needed to definitively predict the significance, type, onset, and trajectory of neurodevelopmental impairment in this population. The significant gaps in long-term outcomes data have elucidated the need for prospective, longitudinal investigation of various cognitive domains in homogenous gastroschisis populations to properly evaluate prevalence of neurodevelopmental deficits and guide recommendations for long-term clinical care. KEY POINTS: · Limited literature exists regarding long-term neurodevelopmental outcomes in gastroschisis.. · There is some evidence to suggest worse cognitive behavioral outcomes in gastroschisis over time.. · Developmental surveillance, screening, and evaluation may be beneficial for gastroschisis patients..

Inclusive Teaching Online: Lessons Learned

ABSTRACT This study aimed to understand how students with disabilities were included in online classrooms as teachers reimagined learning during COVID-19 school shutdowns. Through a mixed-methods approach, researchers investigated the implications of COVID-19 restrictions for private school teachers in Dubai, UAE. Dubai private schools provide many different curriculums but present a uniquely homogenous socio-economic school population to study, in addition to ongoing mandates for inclusion during the shift to at-home learning. The study addressed the adaptations made by teachers that could continue to influence practices in the return to in-person learning. Researchers utilised an explanatory-sequential mixed methods approach to data collection. Initial surveys explored the training and experience of teachers, while interview data brought forth the challenges and successes experienced. Quantitative data was analysed using SPSS software and included a factor analysis. The hypothesis tests for seven independent variables revealed several factors that could potentially lead to more successful outcomes. Qualitative results revealed a lack of adequate training and support for the use of inclusive practices and a need for teachers to reflect on pandemic teaching practices. Teachers reported many innovations and inclusive teaching methods; however, many of these new innovative, inclusive practices risk being lost if teachers do not engage in critical reflection.

Connecting the dots: molecular pathways in bicuspid aortopathy explored

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Junta de Andalucía, Ministerio de Ciencia e Innovación Background Bicuspid aortic valve (BAV) is the most common congenital cardiac malformation. It predisposes to thoracic aortic dilatation (TAD), aneurysm and dissection. The current consensus is that the genetic defect that leads to the aortic valve malformation also causes structural anomalies of the ascending aorta. Altered hemodynamics caused by the abnormal valve morphology would accelerate aortic media degeneration. Molecular markers and pathways involved in the aetiology and pathophysiology of bicuspid aortopathy are poorly understood. Objective To elucidate the molecular and cellular mechanisms of the disease and to identify potential predictive molecular markers using a well-established isogenic hamster model (T strain) with a high (∼40%) incidence of BAV TAD. Methods Comparative quantitative proteomics combined with Western blot and morpho-molecular analyses in the ascending aorta of tricuspid aortic valve (TAV) and BAV animals from the T strain and TAV animals from a control strain. This strategy allows exploring independently the genetic and hemodynamic effects on the aorta in genetically homogeneous populations. Results The major molecular defect in the aorta of genetically homogeneous BAV individuals is PI3K/AKT overactivation caused by alterations in the EGF, ANGII and TGF-β signalling pathways. PI3K/AKT affects the downstream eNOS, MAP2K1/2, NF-κB, mTOR and WNT pathways. Most of these alterations are seen in independent patient studies with different clinical presentations, but not in TAV hamsters from the T strain, which mainly show downregulation of the WNT pathway. Conclusions We identify a combination of defective interconnected molecular pathways, directly linked to the central PI3K/AKT pathway, common to both BAV-associated TAD patients and hamsters. The defects indicate a shift of smooth muscle cells towards the synthetic phenotype induced by endothelial-to-mesenchymal transition, oxidative stress and inflammation. WNT signalling represents a genetic factor that may cause aortic structural abnormalities and aneurysm predisposition, whereas hemodynamics is the main trigger of molecular changes, likely determining the progression of aortopathy. We identify twenty-seven novel potential biomarkers with high predictive value.

Long-Term Oncologic Outcomes of Off-Clamp Robotic Partial Nephrectomy for Cystic Renal Tumors: A Propensity Score Matched-Pair Comparison of Cystic versus Pure Clear Cell Carcinoma.

Few data are available on survival outcomes of partial nephrectomy performed for cystic renal tumors. We present the first long-term oncological outcomes of cystic (cystRCC) versus pure clear cell renal cell carcinoma (ccRCC) in a propensity score-matched (PSM) analysis. Our "renal cancer" prospectively maintained database was queried for "cystRCC" or "ccRCC" and "off-clamp robotic partial nephrectomy" (off-C RPN). The two groups were compared for age, gender, tumor size, pT stage, and Fuhrman grade. A 1:3 PSM analysis was applied to reduce covariate imbalance to <10% and two homogeneous populations were generated. Student t- and Chi-square tests were used for continuous and categorical variables, respectively. Ten-year oncological outcomes were compared between the two cohorts using log-rank test. Univariable Cox regression analysis was used to identify predictors of disease progression after RPN. Out of 859 off-C RPNs included, 85 cases were cystRCC and 774 were ccRCC at histologic evaluation. After applying the PSM analysis, two cohorts were selected, including 64 cystRCC and 170 ccRCC. Comparable 10-year cancer-specific survival probability (95.3% versus 100%, p = 0.146) was found between the two cohorts. Conversely, 10-year disease-free survival probability (DFS) was less favorable for pure ccRCC than cystRCC (66.69% versus 90.1%, p = 0.035). At univariable regression analysis, ccRCC histology was the only independent predictor of DFS probability (HR 2.96 95% CI 1.03-8.47, p = 0.044). At the 10-year evaluation, cystRCC showed favorable oncological outcomes after off-C RPN. Pure clear cell variant histology displayed a higher rate of disease recurrence than cystic lesions.

Investigation of postoperative erectile dysfunction in colorectal surgery patients and comparison of results.

Although surgical treatment is curative for colorectal cancers, erectile dysfunction (ED) is one of the complications that affect the patient quality of life. The present study aimed to evaluate sexual dysfunction in patients who underwent anterior resection (AR) and low AR (LAR) surgery secondary to rectosigmoid pathologies in our clinic, to analyze the effective variables, and to compare the results. In the retrospectively designed study, male patients who underwent surgery for malignancy or other surgical pathologies in the General Surgery Clinic between January 2017 and December 2022 were examined. Female gender, patients under 18 years of age, and patients who refused to participate in the study were excluded. The high age of the patient increased the risk of severe ED in the postoperative period. However, surgical technique, alcohol use, American Society of Anesthesiologists (ASA) score, and Clavien-Dindo class were not determinants in the presence of severe ED. ED is an emerging medical problem that affects patients who undergo colorectal surgery adversely both in social and psychological aspects. Discussions on the issue are still ongoing. Clinicians' concerns can be addressed in the future as the number of prospectively designed studies involving more homogeneous and larger populations increases.

#1049 Genetic characteristics of autosomal dominant polycystic kidney disease in a Greek population

Abstract Background and Aims Autosomal dominant polycystic kidney disease (ADPKD) is the predominant monogenic renal genetic disorder, and the fourth leading cause of end stage kidney disease. Confirmatory genetic testing defines the disease, provides prognostic information and may support therapeutic management. This study aims to investigate the genetic characteristics of a substantial cohort of ADPKD patients from a single Greek center. Method Ninety-three patients (46 females, 47 males with a mean age of 34 ± 15 years) were enrolled from 59 distinct families attending the outpatient ADPKD clinic at the Nephrology Department of the General Hospital of Athens “G. Gennimatas.” Genetic analysis included targeted next-generation sequencing (tNGS) of over 600 clinically relevant genes, Sanger sequencing, and Multiplex ligation-dependent probe amplification (MLPA). Whole exome and whole genome sequencing (WES and WGS) studies were conducted in 3 patients with negative results. Magnetic Resonance Imaging (MRI) was performed in 74 out of 93 patients, revealing more than 10 renal cysts in all but one patient. Children with a positive family history (FH) displayed at least one cyst in echography, while two without FH had multiple renal cysts. Results Genetic diagnosis was established in 88 of 93 patients (94.5%). Seventy patients (75%), demonstrated single nucleotide variants (SNVs) and large deletions (4 patients) in the PKD1 gene, whereas SNVs and large deletions (5 patients) in the PKD2 gene were identified in 15 (16%) patients. Additionally, mutations in genes other than PKD1 and PKD2 were identified in 3 patients (3.5%). Two cases, involving a father and son, revealed the presence of a SEC61B variant; the father exhibited more than 10 renal cysts and liver cysts in the MRI, while the son displayed only liver cysts. Additionally, a third patient, a woman with nephrolithiasis and over 10 renal cysts in the MRI, exhibited a SLC3A1 variant. Notably, 5 patients (5.5%) with ADPKD phenotype had negative genetic analyses, despite the application of both WES and WGS in three of these patients. Truncating mutations in PKD1 were observed in 43 of 70 cases, (61%), while the rest (39%) had non-truncating mutations. Detected variants were classified as Pathogenic (45.5%), Likely Pathogenic (36%), and Variants of Uncertain Significance (VUS-13.5%, 12 cases), according to the guidelines of the American College of Medical Genetics and Genomics. Reclassification to Likely Pathogenic could be proposed for 6 out of 12 cases with VUS variants for which family segregation was noted. Finally, 52% and 82% of the detected variants have not been previously reported in ClinVar and gnomAD databases, respectively. Conclusion In this ethnically homogenous population, truncating mutations in the PKD1 gene were the predominant genetic cause of ADPKD, followed by PKD1 non-truncating mutations, PKD2 gene variants and other rare or undefined genetic etiologies.

Walking on a Balance Beam as a New Measure of Dynamic Balance to Predict Falls in Older Adults and Patients with Neurological Conditions.

Beam walking is a new test to estimate dynamic balance. We characterized dynamic balance measured by the distance walked on beams of different widths in five age groups of healthy adults (20, 30, 40, 50, 60years) and individuals with neurological conditions (i.e., Parkinson, multiple sclerosis, stroke, age: 66.9years) and determined if beam walking distance predicted prospective falls over 12months. Individuals with (n = 97) and without neurological conditions (n = 99, healthy adults, age 20-60) participated in this prospective longitudinal study. Falls analyses over 12months were conducted. The summed distance walked under single (walking only) and dual-task conditions (walking and serial subtraction by 7 between 300 to 900) on three beams (4, 8, and 12-cm wide) was used in the analyses. Additional functional tests comprised grip strength and the Short Physical Performance Battery. Beam walking distance was unaffected on the 12-cm-wide beam in the healthy adult groups. The distance walked on the 8-cm-wide beam decreased by 0.34m in the 20-year-old group. This reduction was ~ 3 × greater, 1.1m, in the 60-year-old group. In patients, beam walking distances decreased sharply by 0.8m on the 8 versus 12cm beam and by additional 1.6m on the 4 versus 8cm beam. Beam walking distance under single and dual-task conditions was linearly but weakly associated with age (R2 = 0.21 for single task, R2 = 0.27 for dual-task). Age, disease, and beam width affected distance walked on the beam. Beam walking distance predicted future falls in the combined population of healthy adults and patients with neurological conditions. Based on receiver operating characteristic curve analyses using data from the entire study population, walking ~ 8.0 of the 12m maximum on low-lying beams predicted future fallers with reasonable accuracy. Balance beam walking is a new but worthwhile measure of dynamic balance to predict falls in the combined population of healthy adults and patients with neurological conditions. Future studies are needed to evaluate the predictive capability of beam walking separately in more homogenous populations. Clinical Trial Registration Number NCT03532984.

Clinical trial eligibility of a real-world connective tissue disease cohort: Results from the LEAP cohort

IntroductionClassification criteria aim to identify a homogenous population of patients for research. We aimed to quantify how well phase-III trials in connective tissue diseases (CTDs) represent a real-world cohort. MethodsA comprehensive review of all major published phase-III trials in CTDs was performed (clinicaltrials.gov). Classification criteria utilised most commonly in clinical trials were applied to a multicentre unselected CTD cohort. ResultsThere were 42 CTD trials identified, with no trials in mixed (MCTD) or undifferentiated CTD (UCTD). The majority of trials (N = 38, 90 %) required patients to meet classification criteria for their respective disease. Eight (19.0 %) excluded patients with overlapping CTDs and a further two (4.8 %) excluded specific overlapping features, such as pulmonary arterial hypertension. One study explicitly allowed overlap syndromes. Our real-world CTD cohort included 391 patients. Patients with UCTD or MCTD (91/391, 23.3 %) would be excluded from participation in clinical trials for not having an eligible diagnosis. Of patients with primary Sjögren's syndrome (pSS), SLE, systemic sclerosis (SSc) or idiopathic inflammatory myopathy (IIM), 211/300 (70.3 %) met the classification criteria for their respective diagnosis and 24/211 (11.4 %) met criteria for >1 CTD. In total, 187/391 (47.8 %) would be eligible for recruitment, based upon their physician diagnosis, and most stringent trial eligibility criteria. ConclusionIn an unselected, real-world CTD cohort, up to half of patients are ineligible for clinical trials due to not meeting classification criteria, overlapping features or a lack of trials within their primary disease. To address this inequality in access to novel therapies, clinical trial design should evolve eligibility criteria in CTDs.

Ethnic and Gender Variations in Ischemic Stroke Patterns among Arab Populations in Northern Israel: A Preliminary Exploration towards Culturally Aware Personalized Stroke Care.

The Galilee region of Israel boasts a rich ethnic diversity within its Arab population, encompassing distinct Muslim, Christian, Druze, and Bedouin communities. This preliminary exploratory study uniquely examined potential ethnic and gender differences in ischemic stroke characteristics across these Arab subgroups, which are seldom investigated separately in Israel and are typically studied as a homogeneous "Arab" sector, despite significant variations in their ethnicity, culture, customs, and genetics. The current study aimed to comparatively evaluate stroke characteristics, including recurrence rates, severity, and subtypes, within and across these distinct ethnic groups and between genders. When examining the differences in stroke characteristics between ethnic groups, notable findings emerged. The Bedouin population exhibited significantly higher rates of recurrent strokes than Muslims (M = 0.55, SD = 0.85 vs. M = 0.25, SD = 0.56; p < 0.05). Large vessel strokes were significantly more prevalent among Christians (30%) than Druze (9.9%; p < 0.05). Regarding gender differences within each ethnic group, several disparities were observed. Druze women were six times more likely to experience moderate to severe strokes than their male counterparts (p < 0.05). Interestingly, Druze women also exhibited a higher representation of cardio-embolic stroke (19.8%) compared with Druze men (4.6%; p < 0.001). These findings on the heterogeneity in stroke characteristics across Arab ethnic subgroups and by gender underscore the need to reconsider the approach that views all ethnic groups comprising the Arab sector in Israel as a homogeneous population; instead, they should be investigated as distinct communities with unique stroke profiles, requiring tailored culturally aware community-based prevention programs and personalized therapeutic models. The identified patterns may guide future research to develop refined, individualized, and preventive treatment approaches targeting the distinct risk factors, healthcare contexts, and prevention needs of these diverse Arab populations.

Pengaruh Model Pembelajaran Case Based Learning Terhadap Kemampuan Menulis Teks Eksplanasi Pada Siswa Kelas XI SMA Negeri 3 Medan

This research was carried out with the aim of finding out the effect of the Case Based Learning learning model on the ability to write explanatory text. The population of this study was all students of class XI SMA Negeri 3 Medan, totaling 6 classes. Sampling in this study was carried out randomly, so 2 classes were obtained, namely class XI MIA-2 consisting of 30 students as the experimental class and class XI MIA-5 consisting of 30 students as the control class. From the data collection and processing that has been carried out, it shows that the ability to write explanatory text in class using the conventional model obtained an average value of 67.08 and a standard deviation of 9.87. Apart from that, judging from the normality test results of the Case Based Learning learning model, the results were Lcount&lt;Ltable, namely 0.137&lt;0.161. Then in the conventional learning model Lcount&lt;Ltable is 0.124&lt;0.161. Because Lcount is smaller than Ltable, the two data above are said to be normally distributed. Likewise, from the results of the data homogeneity test, namely Fcount&lt;Ftable, namely 0.51&lt;0.53, the data comes from a homogeneous population. After the normality test and homogeneity test, hypothesis testing is then carried out. From hypothesis testing, the results obtained are Tcount&gt;Ttable with hypothesis test results of 5.85&gt;1.699, then Ho is rejected and Ha is accepted so this proves that the Case Based Learning model is more influential in improving the ability to write explanatory text in class XI students at SMA Negeri 3 Medan .

Psychometric validation of the Danish version of the Major Depression Inventory using data from the Lolland-Falster health study (LOFUS)

Purpose The Major Depression Inventory (MDI) is a widely used self-rating depression scale commonly in primary care in Denmark. It has not been subject to robust psychometric validation in a general population setting. The aim of this study was to evaluate the psychometric measurement properties of the MDI when applied in the general population. Methods We evaluated statistical psychometric validity using modern test theory (confirmatory factor analysis, item response theory models and Rasch measurement theory) testing local independence and differential item function across groups defined by gender, age, education, and chronic disease status. Separate analyses across different strata and across different statistical models were employed. Results Regarding structural validity we consistently identified local dependence for the item two pairs (MDI2,MDI3) and (MDI4,MDI5) across strata. This result was confirmed by bifactor CFA models and item screening. We further identified substantial differential item functioning with respect to age group and with respect to chronic disease. We identified quantified the magnitude of this lack of measurement invariance. Conclusion The MDI is psychometrically valid in homogenous sub populations, but the disclosed evidence of local dependence means that published estimates of its reliability cannot be trusted. The lack of measurement invariance means that the instrument cannot be used to compare individuals or groups unless they are similar in terms of age group and chronic disease status.

An interventional cross-sectional study of electrolyte levels in newborns with hyperbilirubinemia before and after phototherapy in a tertiary care hospital in central India

Introduction This study protocol outlines a comprehensive investigation into the impact of phototherapy on electrolyte levels in newborns with hyperbilirubinemia. With a focus on neonates admitted to the Neonatal Intensive Care Unit (NICU) at Jawaharlal Nehru Medical College and AVBR Hospital, Sawangi, Wardha, Central India, the research aims to contribute valuable insights into the physiological changes associated with this common neonatal condition. The study’s introduction highlights the rationale, significance, and gaps in current knowledge, emphasising the need for a detailed exploration of electrolyte dynamics before and after phototherapy. Method The methodology involves a descriptive, interventional cross-sectional design with a calculated sample size of 264 neonates. Standardised protocols for data collection, including serum electrolyte analysis and urine-specific gravity assessment, will be employed. Inclusion and exclusion criteria are clearly defined to ensure a homogenous study population. Statistical analyses, utilising R Studio 4.3.1 will encompass descriptive statistics, comparative analysis, correlation analysis, and multivariate analysis to explore the nuanced relationships between variables. Rigorous ethical considerations and transparency in reporting will guide the data collection process. Expected Result Anticipated outcomes include a nuanced understanding of changes in serum electrolyte levels following phototherapy and the correlation of these changes with the treatment duration. The study is poised to shed light on the impact of gestational age and birth weight on electrolyte responses. Through rigorous statistical analysis, the research aims to provide evidence-based insights that can inform neonatal care protocols. The anticipated findings hold the potential to influence clinical practices, enhancing the quality of care provided to newborns with hyperbilirubinemia undergoing phototherapy.

Prevalence of the Gingival Phenotype in Adults and Associated Risk Factors: A Systematic Review of the Literature.

The relevance of assessing the gingival phenotype prior to the initiation of periodontal, orthodontic, or prosthetic therapy has been clearly demonstrated. However, publications on this subject are either old or concerned with the means of assessing the gingival phenotype or the main factors likely to modify it. The main objective of this systematic review of the literature was therefore to investigate the prevalence of different gingival phenotypes in adults in good general health and with a healthy periodontium. A systematic review of the literature was performed following the guidelines of PRISMA recommendations using an electronic search strategy on four databases (PubMed, Scopus, Cochrane Library, and Embase) complemented by a manual search. Three independent authors were involved in study selection, data extraction, and bias assessment. Results: Of 807 articles, 17 of them, published between 2012 and 2023, involving 3277 subjects from 11 countries and 9766 dental sites, fulfilled the inclusion criteria. The prevalence of the gingival phenotype could not be determined at the level of an individual or a dental arch because all the publications assessed this phenotype only at the level of certain dental sectors, and were not chosen at random. The maxillary central incisors and maxillary or mandibular first molar sectors were associated with a high and thick gingival phenotype, independently of the dental morphology, gender, and age of adult subjects. Furthermore, in these regions, this gingival phenotype tended to be associated with a thick vestibular bone table. In contrast, maxillary and mandibular incisors and premolars more often had a thin gingival phenotype. For other teeth, the results were less conclusive. It is important not to rely solely on the overall appearance of the dentition but to independently assess the thickness and height of the gingiva at each dental site requiring intervention. Finally, this study highlights a key point, namely the need for further longitudinal studies to determine the prevalence in healthy adults. For practicality and feasibility reasons, these studies should be designed according to therapeutic needs, dental sector by dental sector, and within homogeneous source populations. PROSPERO registration: CRD 42023392602.

Spatial heterogeneity in tumor adhesion qualifies collective cell invasion

Collective cell invasion (CCI), a canon of most invasive solid tumors, is an emergent property of the interactions between cancer cells and their surrounding extracellular matrix (ECM). However, tumor populations invariably consist of cells expressing variable levels of adhesive proteins that mediate such interactions, disallowing an intuitive understanding of how tumor invasiveness at a multicellular scale is influenced by spatial heterogeneity of cell-cell and cell-ECM adhesion. Here, we have used a Cellular Potts model-based multiscale computational framework that is constructed on the histopathological principles of glandular cancers. In earlier efforts on homogenous cancer cell populations, this framework revealed the relative ranges of interactions, including cell-cell and cell-ECM adhesion that drove collective, dispersed, and mixed multimodal invasion. Here, we constitute a tumor core of two separate cell subsets showing distinct intra- and inter-subset cell-cell or cell-ECM adhesion strengths. These two subsets of cells are arranged to varying extents of spatial intermingling, which we call the heterogeneity index (HI). We observe that low and high inter-subset cell adhesion favors invasion of high-HI and low-HI intermingled populations with distinct intra-subset cell-cell adhesion strengths, respectively. In addition, for explored values of cell-ECM adhesion strengths, populations with high HI values collectively invade better than those with lower HI values. We then asked how spatial invasion is regulated by progressively intermingled cellular subsets that are epithelial, i.e., showed high cell-cell but poor cell-ECM adhesion, and mesenchymal, i.e., with reversed adhesion strengths to the former. Here too, inter-subset adhesion plays an important role in contextualizing the proportionate relationship between HI and invasion. An exception to this relationship is seen for cases of heterogeneous cell-ECM adhesion where sub-maximal HI patterns with higher outer localization of cells with stronger ECM adhesion collectively invade better than their relatively higher-HI counterparts. Our simulations also reveal how adhesion heterogeneity qualifies collective invasion, when either cell-cell or cell-ECM adhesion type is varied but results in an invasive dispersion when both adhesion types are simultaneously altered.

BASiCS workflow: a step-by-step analysis of expression variability using single cell RNA sequencing data

Cell-to-cell gene expression variability is an inherent feature of complex biological systems, such as immunity and development. Single-cell RNA sequencing is a powerful tool to quantify this heterogeneity, but it is prone to strong technical noise. In this article, we describe a step-by-step computational workflow that uses the BASiCS Bioconductor package to robustly quantify expression variability within and between known groups of cells (such as experimental conditions or cell types). BASiCS uses an integrated framework for data normalisation, technical noise quantification and downstream analyses, propagating statistical uncertainty across these steps. Within a single seemingly homogeneous cell population, BASiCS can identify highly variable genes that exhibit strong heterogeneity as well as lowly variable genes with stable expression. BASiCS also uses a probabilistic decision rule to identify changes in expression variability between cell populations, whilst avoiding confounding effects related to differences in technical noise or in overall abundance. Using a publicly available dataset, we guide users through a complete pipeline that includes preliminary steps for quality control, as well as data exploration using the scater and scran Bioconductor packages. The workflow is accompanied by a Docker image that ensures the reproducibility of our results.

Immunological isolation and characterization of neuronal progenitors from human dental pulp: A laboratory-based investigation.

Dental pulp stem cells (DPSCs) contain a population of stem cells with a broad range of differentiation potentials, as well as more lineage-committed progenitors. Such heterogeneity is a significant obstacle to experimental and clinical applications. The aim of this study is to isolate and characterize a homogenous neuronal progenitor cell population from human DPSCs. Polysialylated-neural cell adhesion molecule (PSA-NCAM+) neural progenitors were isolated from the dental pulp of three independent donors using magnetic-activated cell sorting (MACS) technology. Immunofluorescent staining with a panel of neural and non-neural markers was used to characterize the magnetically isolated PSA-NCAM+ fraction. PSA-NCAM+ cells were then cultured in Neurobasal A supplemented with neurotrophic factors: dibutyryl cyclic-AMP, neurotrophin-3, B27 and N2 supplements to induce neuronal differentiation. Both PSA-NCAM+ and differentiated PSA-NCAM+ cells were used in Ca2+ imaging studies to assess the functionality of P2X3 receptors as well as membrane depolarization. PSA-NCAM+ neural progenitors were isolated from a heterogeneous population of hDPSCs using magnetic-activated cell sorting and anti-PSA-NCAM MicroBeads. Flow cytometry analysis demonstrated that immunomagnetic sorting significantly increased the purity of PSA-NCAM+ cells. Immunofluorescent staining revealed expression of pan-neuronal and mature neuronal markers, PGP9.5 and MAP2, respectively, as well as weak expression of the mature sensory markers, peripherin and islet1. ATP-induced response was mediated predominately by P2X3 receptors in both undifferentiated and differentiated cells, with a greater magnitude observed in the latter. In addition, membrane depolarizations were also detected in cells before and after differentiation when loaded with fast-voltage-responding fluorescent molecule, FluoVolt™ in response to potassium chloride. Interestingly, only differentiated PSA-NCAM+ cells were capable of spontaneous membrane oscillations. In summary, DPSCs contain a population of neuronal progenitors with enhanced neural differentiation and functional neural-like properties that can be effectively isolated with magnetic-activated cell sorting (MACS).