Comprehensive and Accurate Molecular Profiling of Breast Cancer through mRNA Expression of ESR1, PGR, ERBB2, MKI67, and a Novel Proliferation Signature.

BACKGROUND: An accurate status determination of breast cancer biomarkers (ER, PR, HER2, Ki67) is crucial for guiding patient management. The "gold standard" for assessing these biomarkers in FFPE tissue is IHC, which faces challenges in standardization and exhibits substantial variability. In this study, we compare the concordance of a new commercial RT-qPCR kit with IHC in determining BC biomarker status. METHODS: The performance was evaluated using 634 FFPE specimens, which underwent histological analysis in accordance with standard of care methods. HER2 2+ tumors were referred to ISH testing. An immunoreactive score of ≥2/12 was considered positive for ER/PR and 20% staining was used as a cut-off for Ki67 high/low score. RT-qPCR and results calling were performed according to the manufacturer's instructions. RESULTS: High concordance with IHC was seen for all markers (93.2% for ER, 87.1% for PR, 93.9% for HER2, 77.9% for Ki67 and 80.1% for proliferative signature (assessed against Ki67 IHC)). CONCLUSIONS: By assessing the concordance with the results obtained through IHC, we sought to demonstrate the reliability and utility of the kit for precise BC subtyping. Our findings suggest that the kit provides a highly precise and accurate quantitative assessment of BC biomarkers.

Development of SkinTracker, an integrated dermatology mobile app and web portal enabling remote clinical research studies.

Introduction: In-person dermatology clinical research studies often face recruitment and participation challenges due to travel-, time-, and cost-associated barriers. Studies incorporating virtual/asynchronous formats can potentially enhance research subject participation and satisfaction, but few mobile health tools are available to enable remote study conduct. We developed SkinTracker, a patient-facing mobile app and researcher-facing web platform, that enables longitudinal collection of skin photos, patient reported outcomes, and biometric health and environmental data. Methods: Eight design thinking sessions including dermatologists, clinical research staff, software engineers, and graphic designers were held to create the components of SkinTracker. Following iterative prototyping, SkinTracker was piloted across six adult and four pediatric subjects with atopic dermatitis (AD) of varying severity levels to test and provide feedback on SkinTracker for six months. Results: The SkinTracker app enables collection of informed consent for study participation, baseline medical history, standardized skin photographs, patient-reported outcomes (e.g., Patient Oriented Eczema Measure (POEM), Pruritus Numerical Rating Scale (NRS), Dermatology Life Quality Index (DLQI)), medication use, adverse events, voice diary to document qualitative experiences, chat function for communication with research team, environmental and biometric data such as exercise and sleep metrics through integration with an Apple Watch. The researcher web portal allows for management and visualization of subject enrollment, skin photographs for examination and severity scoring, survey completion, and other patient modules. The pilot study requested that subjects complete surveys and photographs on a weekly to monthly basis via the SkinTracker app. Afterwards, participants rated their experience in a 7-item user experience survey covering app function, design, and desire for participation in future studies using SkinTracker. Almost all subjects agreed or strongly agreed that SkinTracker enabled more convenient participation in skin research studies compared to an in-person format. Discussion: To our knowledge, SkinTracker is one of the first integrated app- and web-based platforms allowing collection and management of data commonly obtained in clinical research studies. SkinTracker enables detailed, frequent capture of data that may better reflect the fluctuating course of conditions such as AD, and can be modularly customized for different skin conditions to improve dermatologic research participation and patient access.

Ziziphus mauritiana-derived nitrogen-doped biogenic carbon dots: Eco-friendly catalysts for dye degradation and antibacterial applications.

In this study, the naturally available Ziziphus Mauritiana was used as a bioresource for the preparation of bifunctional nitrogen doped carbon dots (N-CDs). The doping of nitrogen into the graphitic carbon skeleton and the in-situ formation of N-CDs were systematically identified by the various structural and morphological studies. The green fluorescent N-CDs were used as active catalysts for the removal of Safranin-O dye and achieved 79 % removal efficiency. Furthermore, the prepared N-CDs were used to evaluate antibacterial activity with four different bacterial species, such as Shigella flexneri, Staphylococcus aureus, Streptococcus pyogenes, and Klebsiella pneumoniae. Amongst these, the highest antimicrobial activity was achieved against Klebsiella pneumonia, with a maximum zone of inhibition of 14.6 ± 1.12 at a concentration of 100 g mL-1. Thus, the obtained results demonstrate the cost efficient bifunctional application prospects of N-CDs to achieve significant catalytic and antibacterial activities.

Regulation of ash slagging behavior of palm oil decanter cake by alum sludge addition.

Combustion of palm oil decanter cake (PODC) is a propitious alternative waste to energy means. However, the mono-combustion of PODC prompt severe ash slagging behavior which give rise to reduction in heat transfer and also shorten the lifespan of combustion reactors. In this study, alum sludge (AS) was introduced at different proportion of 30%, 50% and 70% to revamp the slagging characteristics of PODC during combustion. The addition of AS improved ash fusion temperature of PODC during co-combustion as ash fusion temperature increased significantly under high AS dosage. Slagging and fouling indices showed that at 50% AS addition, slagging tendency of the co-combustion ashes can be ignored. The predictive model for PODC-AS combustion showed good correlation coefficient with 0.89. Overall, co-combustion of PODC and AS is an ideal ash related problem-solving route. The proposed PODC slagging preventive method by AS was based on: (1) limited amount of aluminum content in PODC-AS system resulted in development of refractory ash (2) reduction in proportion of basic oxide which act as ash bonding glue played important role in the regulation of slagging (3) reduction of cohesive bond by formation of spongy and porous structure which prevented ash slagging.

Lyme Neuroborreliosis with Intracranial Hypertension and Erythema Multiforme: A Rare Presentation.

A 9-year-old previously healthy boy presented with high-grade intermittent fever, severe headache associated with neck stiffness for 5 days, rash over trunk and extremities for 4 days, vomiting for 3 days and diplopia for 2 days. There was no history of seizures, abnormal body movements, altered sensorium or focal deficits. On examination, he had maculopapular erythematous rashes over the trunk and extremities and erythema multiforme. He had bilateral abducens nerve palsy and the rest of the cranial nerve, sensory and motor examination was normal. He had neck stiffness and positive Kernig's sign. Fundus examination showed grade 4 papilledema. Cerebrospinal fluid workup revealed elevated opening pressure, lymphocytic pleocytosis, normal protein and glucose levels. Neuroimaging showed features suggestive of intracranial hypertension. Borrelia IgM and IgG antibodies came positive. The uniqueness of our case lies with two rare presenting manifestations of Lyme neuroborreliosis in the same child.

Evaluation of adenosine deaminase activity in serum of cattle and buffaloes in the diagnosis of bovine tuberculosis.

BACKGROUND AND AIM: Bovine tuberculosis (bTB) is a chronic bacterial disease of cattle caused by Mycobacterium bovis. bTB causes severe economic losses resulting from livestock deaths, chronic disease, and trade restrictions. Determination of serum levels of adenosine deaminase (ADA), an enzyme produced by monocytes/macrophages and lymphocytes, has been used in the diagnosis of human TB. This study aimed to evaluate the role of ADA enzyme activity in the diagnosis of bTB. MATERIALS AND METHODS: In this study, a total of 100 animals (cattle and buffaloes) were screened for bTB by comparative intradermal tuberculin test (CITT) and interferon-γ (IFN-γ) test and in serum samples obtained from 100 screened animals, ADA seric activity was evaluated using ADA-MTB kit procured from Tulip Diagnostics. RESULTS: A total of 18 animals were positive TB reactors by CITT, 8 were positive by IFN-γ, and 4 animals were positive by both CITT and IFN-γ. The average ADA value of bTB-positive animals either by CITT, IFN-γ, or both CITT and IFN-γ was 12.55 U/L, 14.8 U/L, and 18.36 U/L, respectively, in CID negative, it was 10.57 U/L and in IFN-γ negative, it was 10.59 U/L. CONCLUSION: The average ADA value of bTB-positive animals positive either by CITT, IFN-γ, or both CITT and IFN-γ was more than the average ADA value in animals negative for bTB by either of the tests.

Stem cell-related gene expression in clonal populations of mesenchymal stromal cells from bone marrow.

Decline in the frequency of potent mesenchymal stem cells (MSCs) has been implicated in ageing and degenerative diseases. Increasing the circulating stem cell population can lead to renewed recruitment of these potent cells at sites of damage. Therefore, identifying the ideal cells for ex vivo expansion will form a major pursuit of clinical applications. This study is a follow-up of previous work that demonstrated the occurrence of fast-growing multipotential cells from the bone marrow samples. To investigate the molecular processes involved in the existence of such varying populations, gene expression studies were performed between fast- and slow-growing clonal populations to identify potential genetic markers associated with stemness using the quantitative real-time polymerase chain reaction comprising a series of 84 genes related to stem cell pathways. A group of 10 genes were commonly overrepresented in the fast-growing stem cell clones. These included genes that encode proteins involved in the maintenance of embryonic and neural stem cell renewal (sex-determining region Y-box 2, notch homolog 1, and delta-like 3), proteins associated with chondrogenesis (aggrecan and collagen 2 A1), growth factors (bone morphogenetic protein 2 and insulin-like growth factor 1), an endodermal organogenesis protein (forkhead box a2), and proteins associated with cell-fate specification (fibroblast growth factor 2 and cell division cycle 2). Expression of diverse differentiation genes in MSC clones suggests that these commonly expressed genes may confer the maintenance of multipotentiality and self-renewal of MSCs.

Cellular senescence and longevity of osteophyte-derived mesenchymal stem cells compared to patient-matched bone marrow stromal cells.

This study aimed to determine the cellular aging of osteophyte-derived mesenchymal cells (oMSCs) in comparison to patient-matched bone marrow stromal cells (bMSCs). Extensive expansion of the cell cultures was performed and early and late passage cells (passages 4 and 9, respectively) were used to study signs of cellular aging, telomere length, telomerase activity, and cell-cycle-related gene expression. Our results showed that cellular aging was more prominent in bMSCs than in oMSCs, and that oMSCs had longer telomere length in late passages compared with bMSCs, although there was no significant difference in telomere lengths in the early passages in either cell type. Telomerase activity was detectable only in early passage oMSCs and not in bMSCs. In osteophyte tissues telomerase-positive cells were found to be located perivascularly and were Stro-1 positive. Fifteen cell-cycle regulator genes were investigated and only three genes (APC, CCND2, and BMP2) were differentially expressed between bMSC and oMSC. Our results indicate that oMSCs retain a level of telomerase activity in vitro, which may account for the relatively greater longevity of these cells, compared with bMSCs, by preventing replicative senescence.

Post-Traumatic Stress Disorder in subjects with schizophrenia and bipolar disorder.

The purpose of this study was to identify subjects with Post-traumatic Stress Disorder (PTSD) consequent to hallucinations and delusions and the experiences related to psychosis in schizophrenic and bipolar subjects. Schizophrenic and bipolar subjects were given questionnaires in order to evaluate PTSD incidence and symptoms. Subjects with classical types of trauma were excluded. Depression and stress scales were also answered. About one-third of schizophrenic subjects and one-half of bipolar subjects met PTSD criteria on the Penn PTSD Inventory. Hallucinations and delusions were identified as traumatic events in 60% of subjects with schizophrenia, but in only 15% of the subjects with bipolar disorder. Also, childhood abuse and various present stressors may contribute to the current PTSD symptomatology. Increases in PTSD scale scores were paralleled by increases in Beck depression scale scores. This study underscores the need for mental health clinicians to be sensitive to patients' illness experiences and to be aware of the therapeutic implications in treating PTSD in subjects with schizophrenia and bipolar illnesses.