Search Results (479)

Background/Objectives: Accurate and rapid detection of Mycobacterium tuberculosis complex (MTBC) and drug resistance is essential for effective tuberculosis (TB) management, particularly in high-burden settings. The Cobas^® MTB and Cobas MTB/RIF-INH assays are moderate-complexity nucleic acid amplification tests that detect MTBC and resistance to rifampicin (RIF) and isoniazid (INH). Methods: This study evaluated the clinical diagnostic performance of the Cobas assays on sputum, using liquid culture as the reference standard and Xpert MTB/RIF Ultra (Xpert Ultra) for comparison. Diagnostic accuracy of the Cobas MTB assay on tongue swabs (TS) was also assessed. Results: In a study population (n = 354) with 56% HIV prevalence, the overall sensitivity and specificity of Cobas MTB on sputum was 93.8% (95% CI: 84.8–98.3) and 100% (95% CI: 98.7–100) compared with culture. The assay showed almost perfect agreement with Xpert Ultra (Cohen’s kappa = 0.904). Among HIV-positive participants, sensitivity was 88.2% (95% CI: 72.5–96.7). RIF resistance profiling by Cobas MTB/RIF-INH was fully concordant with culture and Xpert Ultra. Three INH-resistant cases were missed, likely due to genotypic–phenotypic discordance. Although specimen numbers were small, TS demonstrated better diagnostic accuracy when using a diluted (66%) microbial inactivation solution. Conclusions: The Cobas MTB and MTB/RIF-INH assays demonstrated high diagnostic accuracy compared to culture and Xpert Ultra on sputum. Findings support TS as an alternative specimen type for MTBC detection using an optimized protocol. These findings underscore the potential of the Cobas assays as reliable alternatives for TB and resistance diagnostics, particularly in settings where rapid, accurate detection of MTBC and RIF or INH resistance is crucial. Full article

Objectives: Histopathological growth patterns (HGPs) of liver metastases have been shown to possess prognostic significance. To date, only 2 studies have evaluated the reproducibility of HGP assessment. The aim of our study was to assess the interobserver reproducibility of HGP classification in liver metastases. Methods: A retrospective, consecutive, single-center cohort study was conducted, including patients who underwent surgical resection for liver metastases at the University of Szeged between 2011 and 2023. A comprehensive database was established, incorporating basic histopathological data for each case. Histological slides were independently reviewed by 2 pathologists, 3 pathology specialist trainees, and 2 medical students with varying levels of experience in gastrointestinal pathology. Interobserver agreement was evaluated using intraclass correlation coefficients (ICC) and Fleiss’ kappa. Results: The study included resection specimens from 205 patients, comprising 336 metastatic lesions, predominantly of gastrointestinal origin (n = 188). Excellent interobserver agreement was observed among specialist trainees (ICC = 0.911) and board-certified pathologists (ICC = 0.984). Overall agreement among all 7 evaluators was good (ICC = 0.822). Conclusions: Our findings demonstrate that HGPs can be reliably assessed by individuals with at least 2 years of experience in general pathology. To our knowledge, this is the first study to include the largest number of board-certified pathologists and pathology specialist trainees in a HGP reproducibility analysis. Additionally, no comprehensive literature review on this topic has been previously conducted. Full article

Background: Antinuclear antibodies (ANAs) play a crucial role in diagnosing systemic autoimmune rheumatic diseases, particularly systemic lupus erythematosus. The recommended standard for ANA detection is indirect immunofluorescence testing (IIFT) using human epithelial (HEp-2) cells. Since visual interpretation (VI) of IIFT images is time-consuming and labor-intensive, research is focusing on automated interpretation systems that use artificial intelligence (AI). Methods: Consecutive serum samples (number of sera = 143) from routine clinical care were collected from patients visiting our tertiary rheumatology center. ANA were detected by IIFT with visual interpretation and compared with IIFT using the AI-based interpretation system akiron^® NEO (Medipan, 15827 Blankenfelde-Mahlow, Germany). ANA titer levels and patterns were analyzed according to the Competent Level of the International Consensus on ANA Pattern classification. Results: Agreement of positive/negative ANA discrimination between AI-aided and VI-IIFT at the recommended cut-off of 80 was good (Cohen’s kappa [κ] 0.69) but significantly different (McNemar test, p < 0.0001). At a cut-off of ≥1/80, the agreement was improved (κ 0.76) and the difference between both methods was non-significant (p = 1.0000). The ANA pattern recognition agreement between both approaches was moderate (κ = 0.54). The direct comparison using only the akiron^® NEO HEp-2 cell ANA assay revealed a good agreement (0.67), which improved to very good (κ = 0.80) when differences between ANA patterns anti-cell (AC)4/5 and AC2 were neglected. Notably, titer levels in the automated evaluations were frequently assessed at higher values than in the gold standard interpretation. Conclusions: Our study demonstrates a good agreement for positive/negative ANA discrimination. ANA pattern recognition by AI-aided interpretation showed moderate to very good agreement with VI. Further research and algorithm refinement (e.g., improved pattern recognition and titer calibration) are necessary to support its future implementation as a reliable screening method. Full article

Tetranychus mexicanus (McGregor, 1950) (Tetranychidae) is considered one of the primary phytosanitary problems in passion fruit crops, resulting in significant production losses. Understanding the impact of this mite species’ activity on the physiology of passion fruit plants can serve as a basis for developing sustainable management strategies. With this in mind, this research sought to analyze, using supervised and unsupervised machine learning models, how T. mexicanus mite infestation influences gas exchange, chlorophyll “a” and chlorophyll “b” levels, fluorescence, and thermal response of passion fruit plants. We tested the hypothesis that juvenile and adult mites alter the physiological and thermal response patterns of plants. Only the variables related to the fluorescent response (Fo, Fm, and Fv) had a significant relationship with mite infestation. In the joint comparison of multiple fluorescent variables, there were differences between the treatments of plants infested and not infested by T. mexicanus. The variables’ initial fluorescence (Fo), maximum fluorescence (Fm), and variable fluorescence (Fv) of chlorophyll a had a direct negative impact on both reproductive activity, as measured by the number of eggs and nymphs produced, and the total number of mites found. The unsupervised model based on multidimensional scaling with the k-means algorithm revealed a clear separation between the groups of infested passion fruit plants (Group 1) and healthy plants (Group 2). The Fo response was described with high accuracy for the reproductive rate (75%) and total infestation of eggs, nymphs, and adults of the mites (99.99%). Kappa values were moderate (Kappa = 0.50) and high (Kappa = 0.99) for reproductive and total rates of T. mexicanus, respectively. Additionally, the thermal response revealed that the infested passion fruit plants had a median temperature of 25.1 °C, compared to a median temperature of 25.7 °C, with notable differences between these medians. Therefore, the T. mexicanus mite altered both the fluorescent and thermal patterns of passion fruit plants. Our findings have implications for the development of early detection tools and the generation of future resistance breeding. Full article

Inflammatory muscle loss results from excessive inflammatory responses, causing muscle damage and weakness. In the current investigation, we evaluated the protective effects of diphlorethohydroxycarmalol (DPHC) against tumor necrosis factor-alpha (TNF-α)-induced skeletal muscle inflammation and muscle loss and elucidated the underlying mechanisms. Furthermore, the effect of DPHC on swimming performance was confirmed under TNF-α-induced inflammatory muscle loss-conditioned zebrafish by assessing the swimming number, distance moved, time spent swimming, frequency of swimming zebrafishes in an upstream swim track (Zone A). In vivo behavioral endurance test results indicated that TNF-α treatment significantly decreased the number of swimming zebrafish and swimming distance in Zone A compared with the Control. Meanwhile, the DPHC treatment significantly increased the number of swimming zebrafish and swimming distance in Zone A compared to TNF-α-induced zebrafish. These findings indicate that DPHC treatment effectively improved the swimming performance of TNF-α-induced zebrafish. In an additional study, TNF-α significantly induced inflammatory muscle loss by upregulating nuclear factor kappa light chain enhancer of activated B cells (NF-κB) mitogen activated protein kinase (MAPK) associated proteins and MuRF-1 in the skeletal muscle tissues of TNF-α-induced zebrafish. However, DPHC administration significantly counteracted TNF-α-induced inflammation and muscle loss by downregulating NF-Κb and MAPK-associated proteins, as well as the muscle degradation-related proteins MuRF-1 and MAFbx, in the skeletal muscle tissues of TNF-α-induced zebrafish. In summary, our research findings demonstrated that DPHC from Ishige okamurae could be used for the development of nutraceuticals or functional foods targeting inflammatory muscle loss. Full article

Background/Objectives: In many low- and middle-income countries (LMICs), including Bosnia and Herzegovina, oncology services are constrained by a limited number of specialists and uneven access to evidence-based care. Artificial intelligence (AI), particularly large language models (LLMs) such as ChatGPT, may provide clinical decision support to help standardize treatment and assist clinicians where oncology expertise is scarce. This study aimed to evaluate the concordance, safety, and clinical appropriateness of ChatGPT-generated treatment recommendations compared to decisions made by a multidisciplinary team (MDT) in the management of newly diagnosed breast cancer patients. Methods: This retrospective study included 91 patients with newly diagnosed, treatment-naïve breast cancer, presented to an MDT in Bosnia and Herzegovina in 2023. Patient data were entered into ChatGPT-4.0 to generate treatment recommendations. Four board-certified oncologists, two internal and two external, evaluated ChatGPT’s suggestions against MDT decisions using a 4-point Likert scale. Agreement was analyzed using descriptive statistics, Cronbach’s alpha, and Fleiss’ kappa. Results: The mean agreement score between ChatGPT and MDT decisions was 3.31 (SD = 0.10), with high consistency across oncologist ratings (Cronbach’s alpha = 0.86). Fleiss’ kappa indicated moderate inter-rater reliability (κ = 0.31, p < 0.001). Higher agreement was observed in patients with hormone receptor-negative tumors and those treated with standard chemotherapy regimens. Lower agreement occurred in cases requiring individualized decisions, such as low-grade tumors or uncertain indications for surgery or endocrine therapy. Conclusions: ChatGPT showed high concordance with MDT treatment plans, especially in standardized clinical scenarios. In resource-limited settings, AI tools may support oncology decision-making and help bridge gaps in clinical expertise. However, careful validation and expert oversight remain essential for safe and effective use in practice. Full article

Schizophrenia is a severe recurrent chronic disease that affects a large number of patients. Numerous genetic and epigenetic factors are involved in the pathogenesis of this disease. The involvement of magnesium and zinc has been relatively little studied and often underestimated. The main mechanisms by which zinc and magnesium are involved in the pathogenesis of these diseases is their influence on the neurotransmitter systems at the cerebral level (dopaminergic, glutamatergic, serotoninergic, GABAergic, catecholaminergic and cannabinoid systems). The action of many other factors involved in one form or another in the pathogenesis of schizophrenia is influenced by magnesium and zinc. Among these factors, we mention neuroinflammation, oxidative stress, nuclear factor kB (NF-kappaB), galanin, brain-derived neurotrophic factor (BDNF), substance P(SP), oxytocin, ACTH, prolactin and others. There are also data related to some interactions between antipsychotic medication and the two cations, as well as to disturbed physiological processes (sleep, appetite) in patients with schizophrenia. The existing data show that the concentrations of the two cations must always be determined and the deficits immediately corrected. Full article

Background/Objectives: In 2017, the Canadian Government updated labeling requirements for prepackaged products to include potassium as a mandatory nutrient. Higher potassium intakes are beneficial in the general population, but for those with hyperkalemia, a lower potassium intake is recommended. Methods: The Canadian Food Inspection Agency (CFIA) collects food products and analyzes them to determine their potassium content. The authors requested data collected by the CFIA between January 2005 and November 2023 through an Access to Information request (A-2023-00410). Paired-sample two-sided t-tests were used to compare the difference between the labeled and analyzed potassium contents. Cohen’s Kappa was also used to assess agreement between values. Results: Data were available for 406 food items, with 376 having a labeled and analyzed potassium value. The number of samples within each product type was not equally spread; 60% of samples (243/405) were considered dairy analogs—comprising either plant-based milk or cheese products. The mean difference between analyzed and labeled potassium content was statistically significant at 15 mg per serving (SD, 68 mg; 95% CI, 8–22 mg; p < 0.001). Cohen’s Kappa suggested moderate agreement between labeled and analyzed values (κ = 0.376; 95% CI, 0.305–0.447; p < 0.001). A total of 271 (69.7%) products exceeded a ±10% difference, with 90 (23.9%) over-reporting potassium and 181 (48.1%) under-reporting potassium. Conclusions: The total number of products that were compliance-tested for potassium in Canada was relatively low and skewed disproportionately toward plant-based dairy analogs. Most products had labeled potassium values that differed from the lab-analyzed values, with a greater tendency to under-report vs. over-report potassium content. This suggests that at least some labels may not be accurate enough to correctly identify high-potassium foods for those who are following a low-potassium diet. Full article

In recent years, gut–brain axis signaling has been recognized as an essential factor modifying behavior, mood, cognition, and cellular viability under physiological and pathological conditions. Consequently, the intestinal microbiome has become a potential therapeutic target in neurological and psychiatric disorders. The microbiota-derived metabolite of tryptophan (Trp), indole-3-propionic acid (IPA), was discovered to target a number of molecular processes and to impact brain function. In this review, we outline the key mechanisms by which IPA may affect neuronal activity and survival and provide an update on the evidence supporting the neuroprotective action of the compound in various experimental paradigms. Accumulating data indicates that IPA is a free radical scavenger, a ligand of aryl hydrocarbon receptors (AhR) and pregnane X receptors (PXR), and an anti-inflammatory molecule. IPA decreases the synthesis of the proinflammatory nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), tumor necrosis factor-α (TNF-α), and other cytokines, reduces the generation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome, and enhances the synthesis of neurotrophic factors. Furthermore, produced in the gut, or administered orally, IPA boosts the central levels of kynurenic acid (KYNA), a neuroprotective metabolite of Trp. IPA reduces the release of proinflammatory molecules in the gut, breaking the gut–inflammation–brain vicious cycle, which otherwise leads to neuronal loss. Moreover, as a molecule that easily enters central compartment, IPA may directly impact brain function and cellular survival. Overall, the gathered data confirms neuroprotective features of IPA, and supports its potential use in high-risk populations, in order to delay the onset and ameliorate the course of neurodegenerative disorders and cognitive impairment. Clinical trials evaluating IPA as a promising therapeutic add-on, able to slow down the progress of neurodegenerative disorders such as Alzheimer’s or Parkinson’s disease and to limit the morphological and behavioral consequences of ischemic stroke, are urgently needed. Full article

Swiprosin-1 (SWS1/EFhd2) is a calcium-binding adaptor protein involved in cytoskeletal regulation, but its physiological role in bone homeostasis remains largely undefined. To elucidate its function in osteoclast biology, we examined SWS1 expression and activity during osteoclastogenesis using primary murine bone marrow-derived macrophages, siRNA-mediated knockdown, and SWS1 knockout (KO) mice. SWS1 was predominantly localized to the nucleus in precursor cells and redistributed to the F-actin ring in mature osteoclasts. Receptor activator of nuclear factor-kappa B ligand stimulation significantly downregulated SWS1 mRNA expression. Loss of SWS1 enhanced osteoclast formation, F-actin ring integrity, and bone resorption, accompanied by elevated expression of osteoclastogenic markers. In vivo, male SWS1 KO mice exhibited deteriorated trabecular bone microarchitecture with increased osteoclast numbers. Mechanistically, SWS1 deficiency intensified αvβ3 integrin-associated cytoskeletal signaling and upregulated Akt, MAPK, NF-κB, and PLCγ2 pathways. These results indicate that SWS1 negatively regulates osteoclast differentiation and function by restraining cytoskeletal reorganization and downstream signaling. Collectively, our findings establish SWS1 as a novel modulator of osteoclast activity and a potential therapeutic target for osteolytic bone disorders. Full article

Background: Electronic monitoring adherence devices (EAMDs) are increasingly being utilized in various healthcare settings to track medication adherence. Objective: To determine the accuracy of the Sensal Health MyAide™ Smart Doc in capturing dose removal from the vial, specifically the time of dose removal and the number of pills removed for each actuation of the device. Methods: This validation study compares the device’s recording of dose withdrawals from a prescription vial by simulated patients against reference documentation reported using MS Forms by the participants. Three participants completed a 4-day study consisting of two non-consecutive 1 h sessions per day encompassing six actuations from the prescription vial to be captured by the Sensal Health MyAide™ Smart Dock after their informed consent was obtained. Statistical analysis included percent agreement and Cohen’s kappa assessing agreement between user-reported data and electronic measurement data recorded by the MyAide™ Smart Dock. Outcome measures included confirmation of the specific user, time of dose removal (±1 min), and the number of pills withdrawn. Results: Three subjects were recruited to provide data for a total of 144 actuations. The study found perfect 100% agreement across the number of pills withdrawn and specific users withdrawing the pills and 99% agreement for the time of administration. The Cohen’s kappa values for the outcome measures were 1.00 (95%CI [1.00, 1.00]) for the number of pills dispensed and specific user and 0.993 (95%CI [0.990, 0.996]) for the time of administration. Conclusions: This study found that the Sensal Health MyAide™ Smart Dock can accurately record the time of administration, the number of pills dispensed, and the identity of the user dispensing the pills. Full article

A multicenter molecular biomarker survey was conducted in Multiple Sclerosis (MS) centers across Central-Eastern European countries, encompassing a population of 107 million. Our aim was to provide a “snapshot” for future studies investigating the use of molecular biomarkers in MS. A self-report questionnaire was distributed via email to MS centers in seven Central-Eastern European countries (Croatia, Czech Republic, Poland, Romania, Serbia, Slovakia, and Slovenia) and to four reference centers (two in Austria, one in Germany, and one in Denmark), focusing on cerebrospinal fluid (CSF) analysis and molecular biomarkers in MS. Responding centers routinely request CSF oligoclonal band (OCB) testing in suspected MS cases, although no consensus exists on the number of CSF-restricted bands required to define OCB positivity, either within or between countries. More than half of the surveyed centers in the Czech Republic, Slovakia, Slovenia, and the reference centers request kappa free light chain (κFLC) testing in patients with suspected MS. Neurofilament light chain (NfL) is frequently used as a molecular biomarker for MS in Romania, Slovakia, and the reference centers. In summary, besides the use of CSF-specific OCB there is no consensus among the surveyed countries regarding the use of molecular biomarkers in MS. Full article

Context: It has been claimed that recently, in England, the places with the greatest amount of housing built were the places that least needed them. This is an accusation that has echoes in a number of countries around the globe. The lack of construction leads to greater unaffordability and a lower level of economic activity than could have been achieved if labour, particularly those with high human capital, was not so constrained as to where they could afford to live. The recent National Planning Policy Framework for England imposes mandatory targets on housing planning authorities. As such, the following question is raised: will the targets result in additional residential homes being located in places of greater need than the prevailing pattern? Research Questions: The paper sets out to consider the spatial mismatch between housing additions and national benefit in terms of unaffordability and productivity. Specifically, do the concentrations of high and/or low rates of the prevailing rates of additional dwellings and the target rates of adding dwellings correspond with the clusters of high and/or low unaffordability and productivity? A further question considered is: does the spatial distribution of additional dwellings match the clusters of population growth? Method: The values of the variables are transformed at the first stage into Anselin’s LISA categories. LISA maps can reveal unusually high spatial concentrations of values, or clusters. The second stage entails comparing sets of the transformed data for agreement of the classifications. An agreement coefficient is provided by Fleiss’s kappa. Data: The data used is of additional dwellings, the total number of dwellings, population estimates, gross value added per hour worked (productivity data), and house price–earnings ratios. The period of study covers the eight years prior to 2020 and the two years after, omitting 2020 itself due to the unusual impact on economic activity. All the data is at local authority district level. Findings: The hot and cold spots of additional dwellings do not correspond those of house price–earnings ratios or productivity. However, population growth hot spots show moderate agreement with those of where additional dwellings are concentrated. This is in line with findings from elsewhere, suggesting that population follows housing supply. Concentrations of districts with relatively high targets per unit of existing stocks are found correspond (agree strongly) with clusters of house price–earnings ratios. Links between productivity and housing are much weaker. Conclusions: The strong link between targets and affordability suggests that if the targets are met, the claim that the places that build the most housing are the places that least need them can be challenged. That said, house-price–earnings ratios present a view of unaffordability that will favour greater building in the countryside rather than cities outside of London, which runs against concentrating new housing in urban areas consistent with fostering clusters/agglomerations implicit in the new modern industrial strategy. Full article

Background/Objectives: First-trimester referral scans in high-risk pregnancies are performed by expert fetal medicine operators using an extended protocol that includes direct fetal heart assessment. This study evaluated inter-operator agreement in characterizing the four-chamber view (4CV) and three vessels and trachea view (3VTV) using color Doppler during such scans in both normal and abnormal cases. Methods: Two independent operators and a fetal cardiologist, all blinded to final diagnoses, retrospectively reviewed 2D images and video clips of the 4CV and 3VTV in 90 fetuses (45 with congenital heart disease [CHD] and 45 controls). The 4CV was classified into four patterns: (1) two atrioventricular (A-V) inflows of similar size, (2) one A-V inflow filling two ventricles, (3) one A-V inflow filling one ventricle, and (4) two A-V inflows with disproportion. The 3VTV was assessed for (1) normal V-sign, (2) abnormal vessel number, (3) abnormal vessel dimension, (4) abnormal spatial relationships, and (5) ductal dependence. Agreement was measured using Cohen’s Kappa. Results: Perfect agreement (K = 1) was seen in normal cases. In CHD cases, inter-operator and operator–cardiologist agreement was almost perfect for 4CV (K = 0.83–0.96) and substantial for 3VTV (K = 0.77–0.80). The lowest agreement occurred with ventricular disproportion in 4CV and abnormalities in vessel number and size in 3VTV. Conclusions: Expert operators show strong agreement in interpreting 4CV and 3VTV patterns in first-trimester scans using color Doppler. However, certain abnormalities—particularly ventricular disproportion and vessel anomalies—remain challenging to consistently interpret. Full article

Background: Microbial analyses of tissue samples are of paramount importance for diagnostic and therapeutic purposes in the course of septic revision arthroplasty. Isolation and identification of the causative pathogens pave the way for successful treatment of periprosthetic joint infections, which necessitates a reliable microbiological workup. It is unknown if there are inconsistencies in pathogen detection and differentiation between accredited laboratories in the context of septic revision arthroplasty. Methods: Tissue samples of forty consecutive patients undergoing septic total hip and knee revision surgery were sent to two different accredited and certified laboratories and tested for pathogen growth and bacterial differentiation. Results: Each institution analyzed 200 specimens. Twenty-five patients (62.5%) showed consistent results between laboratories. Diverging results were observed in 15 of 40 patients (37.5%). Of these, three individuals showed pathogen growth in only one laboratory. In 12 patients with discrepant results, laboratory analyses revealed a partly different pathogen spectrum. With regard to clinical impact and infection eradication, the respective differences implicated a therapeutic response by a change of the administered postoperative antibiotic treatment in five (12.5%) of the patients. The kappa correlation coefficient indicated a slight value in terms of data consistency between institutions (k = 0.227, p = 0.151). Conclusions: The majority of evaluated samples show comparable results with regard to microbiological evaluation. Nevertheless, a substantial number of specimens were classified differently. The observed discrepancies pose a challenge for postoperative decision-making. Against this background, standardized microbiological protocols remain mandatory for a conclusive clinical implication to eradicate PJI. Full article