Robotic Versus Manual Electrode Insertion in Cochlear Implant Surgery: An Experimental Study.

Objectives: This experimental study compares the precision and surgical outcomes of manual versus robotic electrode insertions in cochlear implantation.

Methods: Conducted on formalin-fixed cadaveric heads, the study involved nine senior neurotologists performing both manual and robotic insertions.

Results: The results showed no statistically significant difference between the two methods in insertion angle, cochlear coverage, or electrode coverage.

An unexpected opportunist: infection in an immunocompetent patient.

is an uncommon opportunistic fungal pathogen primarily affecting immunocompromised individuals. While rare, cases have been reported in immunocompetent patients. We present a documented case of invasive infection in an immunocompetent patient with no previous medical history.

A group 3 medulloblastoma stem cell program is maintained by OTX2-mediated alternative splicing.

OTX2 is a transcription factor and known driver in medulloblastoma (MB), where it is amplified in a subset of tumours and overexpressed in most cases of group 3 and group 4 MB. Here we demonstrate a noncanonical role for OTX2 in group 3 MB alternative splicing. OTX2 associates with the large assembly of splicing regulators complex through protein-protein interactions and regulates a stem cell splicing program.

From Antibodies to Artificial Intelligence: A Comprehensive Review of Diagnostic Challenges in Hashimoto's Thyroiditis.

Hashimoto's thyroiditis (HT) poses diagnostic challenges due to its diverse clinical presentation and the intricacies of autoimmune thyroid diseases. This comprehensive narrative review explores the evolving landscape of diagnostic challenges in HT, aiming to provide a thorough understanding of the complexities involved in its diagnosis. The diagnostic criteria for HT involve a multifaceted approach, including clinical features, laboratory findings, and imaging studies.

Effect of Sodium-Glucose Cotransporter 2 Inhibitors on the 24-Hour Ambulatory Blood Pressure in Patients With Type 2 Diabetes Mellitus and Hypertension: An Updated Meta-Analysis.

Objective: Sodium-glucose cotransporter 2 inhibitors (SGLT2i), initially developed for type 2 diabetes mellitus (DM) treatment, have shown potential benefits beyond glycemic control, including a positive impact on the blood pressure (BP). This meta-analysis aimed to evaluate their effects on patients with type 2 DM and hypertension.

Methods: We searched the PubMed, Google Scholar, and Cochrane databases for relevant randomized controlled trials published until May 31, 2023.

Compensatory cross-talk between autophagy and glycolysis regulates senescence and stemness in heterogeneous glioblastoma tumor subpopulations.

Despite tremendous research efforts, successful targeting of aberrant tumor metabolism in clinical practice has remained elusive. Tumor heterogeneity and plasticity may play a role in the clinical failure of metabolism-targeting interventions for treating cancer patients. Moreover, compensatory growth-related processes and adaptive responses exhibited by heterogeneous tumor subpopulations to metabolic inhibitors are poorly understood.

Metabolism-based targeting of MYC via MPC-SOD2 axis-mediated oxidation promotes cellular differentiation in group 3 medulloblastoma.

Group 3 medulloblastoma (G3 MB) carries the worst prognosis of all MB subgroups. MYC oncoprotein is elevated in G3 MB tumors; however, the mechanisms that support MYC abundance remain unclear. Using metabolic and mechanistic profiling, we pinpoint a role for mitochondrial metabolism in regulating MYC.

Analysing the behavioural, psychological, and demographic determinants of financial decision making of household investors.

Adding to the behavioural science domain, the principal idea behind the study is to investigate the impact of an array of behavioural, psychological, and demographic factors on financial decision making. The study utilizes a structured questionnaire to collect the opinions of 634 investors using a blend of random and snowball sampling techniques. The partial least squares structural equation modelling has been used to test hypotheses.

COVID-19 and stock returns: Evidence from the Markov switching dependence approach.

This paper aims to investigate the regime-switching and time-varying dependence between the COVID-19 pandemic and the US stock markets using a Markov-switching framework. It makes two contributions to the empirical literature by showing that: (a) the variations of the daily reported COVID-19 cases and cumulative COVID-19 deaths induced asymmetric lower (left) and upper (right) tail dependence with the stock markets, and its left and right tail dependence exhibited significant time-varying trends; and (b) the left and right tail dependence between the stock markets and the pandemic exhibited significant regime-switching behaviours, with its switching probabilities in the higher tail dependence stage all being greater than in the lower tail dependence stage after 1 December 2019. Moreover, given that there is concurrent but significant financial market reaction to any unexpected emergence of a transmittable respirational disease or a natural calamity, the outcomes have some vital implications to market players and policymakers.

Biallelic variants in PAX3 cause Klein syndrome.

Waardenburg syndrome is a group of genetic conditions that can cause hearing loss and pigmentation deficiency of the hair, skin, and eyes. Klein-Waardenburg syndrome (Waardenburg syndrome type 3) represents a distinct presentation of Waardenburg syndrome type 1 and includes musculoskeletal abnormalities in addition to dystopia canthorum hearing loss and pigmentary changes. Heterozygous or homozygous variants in the PAX3 gene cause Klein-Waardenburg syndrome.

Anatomy-Based Frequency Allocation in Cochlear Implantation: The Importance of Cochlear Coverage.

Objectives/hypothesis: This study aimed to compare the predicted anatomy-based frequency allocation of cochlear implant electrodes with the default standard frequencies.

Study Design: Retrospective study.

Methods: A retrospective analysis was performed using computed tomography (CT) images of patients who received cochlear implants at a tertiary referral center.

The Breast Tumor Microenvironment: A Key Player in Metastatic Spread.

The tumor microenvironment plays a pivotal role in the tumorigenesis, progression, and metastatic spread of many cancers including breast. There is now increasing evidence to support the observations that a bidirectional interplay between breast cancer cells and stromal cells exists within the tumor and the tumor microenvironment both at the primary tumor site and at the metastatic site. This interaction occurs through direct cell to cell contact, or by the release of autocrine or paracrine factors which can activate pro-tumor signaling pathways and modulate tumor behavior.

Regulation of the proline regulatory axis and autophagy modulates stemness in TP73/p73 deficient cancer stem-like cells.

Cancer stem-like cells (CSLCs) reside as a small population within tumors, which mostly contain a larger population of differentiated cells. With their unique self-renewing abilities, CSLCs remain refractory to various therapeutic interventions, which otherwise kill differentiated cancer cells, and thus are a major culprit behind cancer treatment failures and cancer relapse. Recently, the process of macroautophagy/autophagy has emerged as a potential therapeutic target for eliminating CSLCs, as autophagic homeostasis has been discovered to play an important role in the growth of cancer and normal stem cells, and is required for the maintenance of the non-differentiated state of CSLCs.

TAp73 Modifies Metabolism and Positively Regulates Growth of Cancer Stem-Like Cells in a Redox-Sensitive Manner.

Purpose: Stem-like cancer cells, with characteristic self-renewal abilities, remain highly refractory to various clinical interventions. As such, stemness-inhibiting entities, such as tumor suppressor p53, are therapeutically pursued for their anticancer activities. Interestingly, similar implications for tumor suppressor TAp73 in regulating stemness features within stem-like cancer cells remain unknown.

HDAC6 differentially regulates autophagy in stem-like versus differentiated cancer cells.

Cancer stem-like cells (CSCs), a small population of pluripotent cells residing within heterogeneous tumor mass, remain highly resistant to various chemotherapies as compared to the differentiated cancer cells. It is being postulated that CSCs possess unique molecular mechanisms, such as autophagic homeostasis, that allow CSCs to withstand the therapeutic assaults. Here we demonstrate that HDAC6 inhibition differentially modulates macroautophagy/autophagy in CSCs as compared to that of differentiated cancer cells.

Phosphoglycerate dehydrogenase inhibition induces p-mTOR-independent autophagy and promotes multilineage differentiation in embryonal carcinoma stem-like cells.

Cancer cells with a less differentiated stem-like phenotype are more resistant to therapeutic manipulations than their differentiated counterparts, and are considered as one of the main causes of cancer persistence and relapse. As such, induction of differentiation in cancer stem-like cells (CSLCs) has emerged as an alternative strategy to enhance the efficacy of anticancer therapies. CSLCs are metabolically distinct from differentiated cells, and any aberration from the intrinsic metabolic state can induce differentiation of CSLCs.

The NAD Salvage Pathway Supports PHGDH-Driven Serine Biosynthesis.

NAD is a key metabolic redox cofactor that is regenerated from nicotinamide through the NAD salvage pathway. Here, we find that inhibiting the NAD salvage pathway depletes serine biosynthesis from glucose by impeding the NAD-dependent protein, 3-phosphoglycerate dehydrogenase (PHGDH). Importantly, we find that PHGDH breast cancer cell lines are exquisitely sensitive to inhibition of the NAD salvage pathway.

Regulation of Cancer and Cancer-Related Genes via NAD.

Significance: NAD is an essential redox cofactor in cellular metabolism and has emerged as an important regulator of a wide spectrum of disease conditions, most notably, cancers. As such, various strategies targeting NAD synthesis in cancers are in clinical trials. Recent Advances: Being a substrate required for the activity of various enzyme families, especially sirtuins and poly(adenosine diphosphate [ADP]-ribose) polymerases, NAD-mediated signaling plays an important role in gene expression, calcium release, cell cycle progression, DNA repair, and cell proliferation.

A randomized controlled trial to assess the effect of a ketamine infusion on tourniquet hypertension during general anaesthesia in patients undergoing upper and lower limb surgery.

Background: Tourniquet hypertension arising from tourniquet inflation remains a primary concern to the anaesthetist. One drug commonly used to manage tourniquet hypertension is ketamine. No studies have examined the effect of ketamine on tourniquet hypertension for a period of more than one hour or an infusion of the same.

Accuracy of Non-Fasting Lipid Profile for the Assessment of Lipoprotein Coronary Risk.

Objective: To determine the diagnostic accuracy of non-fasting lipid profile in the diagnosis of hyperlipidemia, taking fasting lipid profile as gold standard, in adult population.

Study Design: Cross-sectional validation study.

Place And Duration Of Study: Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi, from July to December 2014.