Using routine primary care data in research: (in)efficient case studies and perspectives from the Asthma UK Centre for Applied Research.

Aim: We aimed to identify enablers and barriers of using primary care routine data for healthcare research, to formulate recommendations for improving efficiency in knowledge discovery.

Background: Data recorded routinely in primary care can be used for estimating the impact of interventions provided within routine care for all people who are clinically eligible. Despite official promotion of 'efficient trial designs', anecdotally researchers in the Asthma UK Centre for Applied Research (AUKCAR) have encountered multiple barriers to accessing and using routine data.

Synergistic design of CuO/CoFe₂O₄/MWCNTs ternary nanocomposite for enhanced photocatalytic degradation of tetracycline under visible light.

This study involves a novel CuO/CoFe₂O₄/MWCNTs (CCT) nanocomposite, developed by integrating cobalt ferrite (CoFe₂O₄) and copper oxide (CuO) nanoparticles onto multi-walled carbon nanotubes (MWCNTs), for the degradation of tetracycline (TC) under visible light. The photocatalyst was extensively characterized using XRD, HR-SEM, EDX, HR-TEM, UV-Vis, BET, and PL analysis. The synthesized CoFe₂O₄ and CuO nanoparticles exhibited crystallite sizes of 46.

Scorpion sting-induced malignant middle cerebral artery infarction.

A previously healthy middle-aged man in his 40s with a history of red scorpion envenomation presented to the emergency department for the management of an acute stroke syndrome, involving the left middle cerebral artery (MCA) territory, that developed 12 hours after the scorpion sting. He presented to the hospital 15 hours following the stroke. The activation of the autonomic nervous system by the Indian red scorpion venom is known to produce severe systemic manifestations, including cardiogenic shock and acute pulmonary oedema.

A series of genetically confirmed congenital lipodystrophy and diabetes in adult southern Indian patients.

In this study, we analysed the mutation spectrum in subjects with suspected lipodystrophy using a targeted Next-generation sequencing (NGS) approach. Subjects with suspected lipodystrophy were for screened six genes (AGPAT2, BSCL2, LMNA, PPARG, ZMPSTE24, INSR) and the variants identified were confirmed through Sanger sequencing. The clinical and biochemical parameters were compared among the mutation positive and negative subjects.

Identification of DLK1, a Notch ligand, as an immunotherapeutic target and regulator of tumor cell plasticity and chemoresistance in adrenocortical carcinoma.

Immunotherapeutic targeting of cell surface proteins is an increasingly effective cancer therapy. However, given the limited number of current targets, the identification of new surface proteins, particularly those with biological importance, is critical. Here, we uncover delta-like non-canonical Notch ligand 1 (DLK1) as a cell surface protein with limited normal tissue expression and high expression in multiple refractory adult metastatic cancers including small cell lung cancer (SCLC) and adrenocortical carcinoma (ACC), a rare cancer with few effective therapies.

Advocating Targeted Sequential Screening over Whole Exome Sequencing in 21-Hydroxylase Deficiency.

Objectives: Whole exome sequencing (WES) has emerged as the preferred method for diagnosing a range of Mendelian disorders. Nonetheless, the applicability of WES in genetic diagnosis of 21-hydroxylase deficiency (21-OHD) remains uncertain due to the intricacies involved in molecular analysis of the CYP21A2 gene.

Methods: In this case series, authors report the outcomes of couples or families who underwent WES followed by focused sequential strategy (FSS) targeting CYP21A2 gene hotspot mutations and targeted sequencing of genes associated with Congenital Adrenal Hyperplasia (CAH).

Update in the management of gastroenteropancreatic neuroendocrine tumors.

Neuroendocrine neoplasms are a diverse group of neoplasms that can occur in various areas throughout the body. Well-differentiated neuroendocrine tumors (NETs) most often arise in the gastrointestinal tract, termed gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Although GEP-NETs are still uncommon, their incidence and prevalence have been steadily increasing over the past decades.

The BRCA mutation spectrum among breast and ovarian cancers in India: highlighting the need to screen BRCA1 185delAG among South Indians.

Mutations in BRCA1 and BRCA2 significantly elevate the risk of developing breast and ovarian cancer. Limited data exists regarding the prevalence of BRCA mutations, and optimal, cost-effective testing strategies in developing countries like India. This study aimed to evaluate the utility of a Next Generation Sequencing (NGS) panel for BRCA1/2 mutation testing among women diagnosed with, or at risk of developing hereditary breast and ovarian cancers.

A real-world study of treatment sequences and second-line clinical outcomes in patients with HER2-positive metastatic breast cancer in US community practice.

Purpose: Standard-of-care for HER2-positive metastatic breast cancer (HER2 + mBC) patients consists of trastuzumab ± pertuzumab with chemotherapy in first-line (1L), and ado-trastuzumab emtansine (T-DM1) or the more recently approved trastuzumab deruxtecan (T-DXd) in second-line (2L). Contemporary data on treatment sequencing and real-world effectiveness is limited. This study aims to report 2L treatments and outcomes among HER2 + mBC patients in the United States (US).

Outdoor air pollution and near-fatal/fatal asthma attacks in children: A systematic review.

Background: Globally, observational studies have demonstrated an association between high levels of air pollution and asthma attacks in children. It remains unclear whether and to what extent exposure may be associated with increased near-fatal/fatal attacks.

Objective: To systematically review the evidence for an association between ambient outdoor air pollution and fatal and/or near-fatal asthma (NFA).

Pulmonary Metastasectomy for Adrenocortical Carcinoma-Not If, but When.

Background: Adrenocortical carcinoma (ACC) commonly metastasizes to the lungs, and pulmonary metastasectomy (PM) is utilized due to limited systemic options.

Methods: All ACC patients with initially only lung metastases (LM) from a single institution constituted this observational case series. Kaplan-Meier and Cox proportional hazard analyses evaluated the association with potential prognostic factors and outcomes.

Near-fatal and fatal asthma and air pollution: are we missing an opportunity to ask key questions?

There is an increasing body of evidence supporting the link between asthma attacks and air pollution in children. To our knowledge, there has only been one reported case of a fatal asthma attack in a child associated with air pollution and this was in the UK. This article considers why there is a lack of evidence on fatal/near-fatal asthma and air pollution.

Co prescription of anti-acid therapy reduces the bioavailability of mycophenolate mofetil in systemic sclerosis patients: A crossover trial.

Objective: Mycophenolate mofetil (MMF) is an effective treatment option for interstitial lung disease (ILD) in systemic sclerosis (SSc). Many patients require co-administration of proton pump inhibitors (PPI) or H2 receptor blockers (HRB) because of various gastrointestinal (GI) manifestations in SSc. Co-treatment with PPI or HRB have shown to reduce serum drug levels in post-transplant patients.

Comprehensive analysis of NiFeO/MWCNTs nanocomposite to degrade a healthcare waste - tetracycline.

Tetracycline (TC), a commonly used antibiotic for studying bacterial illnesses in living organisms, poses a significant risk to the aquatic environment. Despite various conventional methods having been attempted to remove TC antibiotics from water solutions, they have not proven effective. Consequently, the focus of the research is on the photocatalytic degradation of TC.

Retrospective study to estimate the prevalence and describe the clinicopathological characteristics, treatments received, and outcomes of HER2-low breast cancer.

Background: Approximately 80% of all breast cancers (BCs) are currently categorized as human epidermal growth factor receptor 2 (HER2)-negative [immunohistochemistry (IHC) 0, 1+, or 2+/in situ hybridization (ISH) negative]; approximately 60% of BCs traditionally categorized as HER2-negative express low levels of HER2. HER2-low (IHC 1+ or IHC 2+/ISH-) status became clinically actionable with approval of trastuzumab deruxtecan to treat unresectable/metastatic HER2-low BC. Greater understanding of patients with HER2-low disease is urgently needed.

Grade Progression and Intrapatient Tumor Heterogeneity as Potential Contributors to Resistance in Gastroenteropancreatic Neuroendocrine Tumors.

Gastroenteropancreatic neuroendocrine neoplasms (NENs) are a heterogenous group of tumors that are incurable when metastatic, regardless of grade. The aim of this article is to understand tumor heterogeneity and grade progression as possible contributors to drug resistance in gastroentropancreatic neuroendocrine tumors (GEP-NETs). Heterogeneity has been observed in the genetic, pathological, and imaging features of these tumors at baseline.

Pharmacist Involvement in an Acute Care of the Elderly Team: Impact on Appropriate Medication Use.

Currently, our institution does not have a full-time pharmacist rounding with the inpatient acute care of the elderly (ACE) team daily. We sought to evaluate the involvement of a clinical pharmacy service within the ACE team and its impact on appropriate medication use. The primary outcome was the number of drug-related problems (DRPs) and potentially inappropriate medications (PIMs) detected by the pharmacist compared with no pharmacist on the ACE team.

GRP78/BiP alleviates oxLDL-induced hepatotoxicity in familial hypercholesterolemia caused by missense variants of LDLR in a HepG2 cellular model.

Background And Aims: The accumulation of misfolded proteins, encoded by genetic variants of functional genes leads to Endoplasmic Reticulum (ER) stress, which is a critical consequence in human disorders such as familial hypercholesterolemia, cardiovascular and hepatic diseases. In addition to the identification of ER stress as a contributing factor to pathogenicity, extensive studies on the role of oxidized Low-Density Lipoprotein (oxLDL) and its ill effects in expediting cardiovascular diseases and other metabolic comorbidities are well documented. However, the current understanding of its role in hepatic insults needs to be revised.

Genetic disruption of mammalian endoplasmic reticulum-associated protein degradation: Human phenotypes and animal and cellular disease models.

Endoplasmic reticulum-associated protein degradation (ERAD) is a stringent quality control mechanism through which misfolded, unassembled and some native proteins are targeted for degradation to maintain appropriate cellular and organelle homeostasis. Several in vitro and in vivo ERAD-related studies have provided mechanistic insights into ERAD pathway activation and its consequent events; however, a majority of these have investigated the effect of ERAD substrates and their consequent diseases affecting the degradation process. In this review, we present all reported human single-gene disorders caused by genetic variation in genes that encode ERAD components rather than their substrates.