Protocol for performing metabolic pathway-based subtyping of breast tumors.

Here, we present a protocol for analyzing the global metabolic landscape in breast tumors for the purpose of metabolism-based patient stratification. We describe steps for analyzing 1,454 metabolic genes representing 90 metabolic pathways and subjecting them to an algorithm that calculates the deregulation score of 90 pathways in each tumor sample, thus converting gene-level information into pathway-level information. We then detail procedures for performing clustering analysis to identify metabolic subtypes and using machine learning to develop a signature representing each subtype. For complete details on the use and execution of this protocol, please refer to Iqbal et al.1.

Feline lung-digit syndrome: A differential diagnosis for shifting, waxing and waning lameness in a cat.

The clinical presentation, cytologic findings, radiographic findings, and postmortem assessment of a cat with primary pulmonary adenocarcinoma with multiple digital metastasis are described. An unusual shifting, waxing and waning pattern of lameness, suspected to be an early manifestation of digital metastasis before any gross lesions were visible, was documented. Initial cytologic finding of a lung nodule was equivocal for diagnosis of neoplasia despite being strongly suspicious. Palliative management was short-lived, with rapid progression culminating in widespread metastasis to multiple digits, muscles, and other organs. The diagnosis of pulmonary adenocarcinoma was confirmed via necropsy and histopathology. Key clinical message: This case report highlights that feline lung-digit syndrome is an important differential diagnosis for an acute, waxing and waning, shifting leg lameness in an older cat. This pattern of lameness should raise the index of suspicion for an underlying primary lung neoplasm, and thoracic imaging (radiographs) should be considered.

Syndrome pulmonaire-digital félin : un diagnostic différentiel des boiteries changeantes, croissantes et décroissantes chez un chatLa présentation clinique, les résultats cytologiques, les résultats radiographiques et l'évaluation post mortem d'un chat atteint d'adénocarcinome pulmonaire primaire avec métastases numériques multiples sont décrits. Un schéma inhabituel de boiterie, variable, croissante et décroissante, suspecté d'être une manifestation précoce de métastases digitales avant que des lésions macroscopiques ne soient visibles, a été documenté. La découverte cytologique initiale d'un nodule pulmonaire était équivoque pour le diagnostic de néoplasie bien qu'elle soit fortement suspecte. La prise en charge palliative a été de courte durée, avec une progression rapide aboutissant à des métastases généralisées à plusieurs doigts, muscles et autres organes. Le diagnostic d'adénocarcinome pulmonaire a été confirmé par autopsie et histopathologie.Message clinique clé :Ce rapport de cas souligne que le syndrome pulmonaire-digital félin est un diagnostic différentiel important pour une boiterie aiguë, croissante et décroissante et mobile des pattes chez un chat ágé. Ce type de boiterie devrait faire suspecter une tumeur primaire du poumon sous-jacente, et une imagerie thoracique (radiographies) devrait être envisagée.(Traduit par Dr Serge Messier).

Nanoparticle-Based Rice Husk Liquid Smoke as Periodontitis Therapy through OPG, RANK, and RANKL Expression.

Introduction: Periodontitis therapy employing nanomaterials with submicron sizes holds promise for enhancing osteogenesis and facilitating periodontal cell proliferation. This study aims to assess the potential of nanoparticle-based rice husk liquid smoke (n-RHLS) in an animal model of periodontitis by evaluating the expression of osteoprotegerin (OPG), receptor activator of nuclear factor-kß (RANK), and receptor activator of nuclear factor-kß ligand (RANKL). Methods: Twenty-eight male Wistar rats were inoculated with 109 CFU/ml of Porphyromonas gingivalis in the sulcus mandibular incisor region to create periodontitis and subsequently treated with n-RHLS while the control with saline. Immunohistochemical staining was performed on the mandibular incisor to assess OPG, RANK, and RANKL expression 2 and 7 days after treatment. Results: OPG expression exhibited a significant increase at both 2 and 7 days, while RANKL expression decreased notably after 7 days of treatment using n-RHLS (p < 0.05). In contrast, RANK expression did not show significant differences compared to the control groups (p > 0.05). Conclusion: Nanostructured liquid smoke derived from rice husk nanoparticles (n-RHLS) demonstrates potential as a therapeutic agent for periodontitis, especially on OPG/RANK/RANKL expression, by modulating OPG and RANKL expression to support periodontal tissue health.

A nanoformulation of cisplatin with arabinoxylan having enhanced activity against hepatocellular carcinoma through upregulation of apoptotic and necroptotic pathways.

Cisplatin is a versatile drug used to treat various types of cancer, but it is associated with high toxicity and resistance problems. Several approaches, including nanotechnology, have been adopted to minimize the toxic effects and to overcome the resistance of cisplatin. Most of the nanoformulations involve the use of synthetic or semisynthetic polymers as drug carriers. In this study arabinoxylan nanoparticles have been investigated as drug reservoirs for intestinal drug delivery. The drug-loaded arabinoxylan nanoparticles (size: ∼1.8 nm, polydispersity index: 0.3 ± 0.04) were prepared and nanoformulation was characterized by various analytical techniques. The nanoformulation was found to be stable (zeta potential: 31.6 ± 1.1 mV). An in vitro cytotoxicity against HepG2 and HEK 293 cell lines was studied. The cell viability analysis showed greater efficacy than the standard cisplatin (IC50: cisplatin 2.4, arabinoxylan nanoformulation 1.3 µg mL-1). The expression profile of carcinogenic markers revealed a six-fold upregulation of MLKL and 0.9-fold down regulation of KRAS, suggesting the activation of the necroptotic pathway by the drug-loaded nanoparticles. The nanoformulation exhibited a sustained release of cisplatin with a cumulative release of ∼40 % (at pH 7.4) and ∼30 % (at pH 5.5) over a period of 12 h with very low initial burst. The study suggests that the use of the new nanoformulation can significantly reduce the required dose of cisplatin without compromising efficacy and more efficient release at basic pH.

Air Pollution: Challenges to Human Health in Pakistan.

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Torus fractures - diagnosis and management.

Torus fractures are a common paediatric injury involving the distal radius. Patients typically present following a fall onto the outstretched hand, with wrist pain as their primary complaint. The principal investigation of choice is a plain radiograph of the wrist joint. These fractures should be managed with a soft-bandage and immediate discharge approach and do not require specialist follow-up. Clinicians have historically had differing views regarding optimal management of torus fractures. It is therefore important for hospital clinicians to uniformly understand the most up-to-date management of this condition. This review provides an overview of the epidemiology, anatomy, diagnosis and management, with an aim to improve outcomes.

Medicinal plants of Southeast Asia with anti-α-glucosidase activity as potential source for type-2 diabetes mellitus treatment.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetes mellitus, a widespread chronic illness, affects millions worldwide, and its incidence is increasing alarmingly, especially in developing nations. Current pharmacological treatments can be costly and have undesirable side effects. To address this, medicinal plants with antidiabetic effects, particularly targeting α-glucosidase for controlling hyperglycaemia in type-2 diabetes mellitus (T2DM), hold promise for drug development with reduced toxicity and adverse reactions. AIM OF THIS REVIEW: This review aims to succinctly collect information about medicinal plant extracts that exhibit antidiabetic potential through α-glucosidase inhibition using acarbose as a standard reference in Southeast Asia. The characteristics of this inhibition are based on in vitro studies. MATERIALS AND METHODS: Relevant information on medicinal plants in Southeast Asia, along with α-glucosidase inhibition studies using acarbose as a positive control, was gathered from various scientific databases, including Scopus, PubMed, Web of Science, and Google Scholar. RESULTS: About 49 papers were found from specific counties in Southeast Asia demonstrated notable α-glucosidase inhibitory potential of their medicinal plants, with several plant extracts showcasing activity comparable to or surpassing that of acarbose. Notably, 19 active constituents were identified for their α-glucosidase inhibitory effects. CONCLUSIONS: The findings underscore the antidiabetic potential of the tested medicinal plant extracts, indicating their promise as alternative treatments for T2DM. This review can aid in the development of potent therapeutic medicines with increased effectiveness and safety for the treatment of T2DM.

Industrially Scalable Textile Sensing Interfaces for Extended Artificial Tactile and Human Motion Monitoring without Compromising Comfort.

Smart wearables with the capability for continuous monitoring, perceiving, and understanding human tactile and motion signals, while ensuring comfort, are highly sought after for intelligent healthcare and smart life systems. However, concurrently achieving high-performance tactile sensing, long-lasting wearing comfort, and industrialized fabrication by a low-cost strategy remains a great challenge. This is primarily due to critical research gaps in novel textile structure design for seamless integration with sensing elements. Here, an all-in-one biaxial insertion knit architecture is reported to topologically integrate sensing units within double-knit loops for the fabrication of a large-scale tactile sensing textile by using low-cost industrial manufacturing routes. High sensitivity, stability, and low hysteresis of arrayed sensing units are achieved through engineering of fractal structures of hierarchically patterned piezoresistive yarns via blistering and twisting processing. The as-prepared tactile sensing textiles show desirable sensing performance and robust mechanical property, while ensuring excellent conformability, tailorability, breathability (288 mm s-1), and moisture permeability (3591 g m-2 per day) for minimizing the effect on wearing comfort. The multifunctional applications of tactile sensing textiles are demonstrated in continuously monitoring human motions, tactile interactions with the environment, and recognizing biometric gait. Moreover, we also demonstrate that machine learning-assisted sensing textiles can accurately predict body postures, which holds great promise in advancing the development of personalized healthcare robotics, prosthetics, and intelligent interaction devices.

Analysis of Correlation Between LncRNA TDRG1 Expression and its Prognosis in Cervical Carcinoma Tissues.

To explore and analyze the correlation between LncRNA TDRG1 expression degree and the prognosis of cervical carcinoma tissues. The cervical cancer tissues and para-carcinoma tissues of 106 patients with cervical carcinoma surgically removed in our hospital were chosen as specimens. LncRNA TDRG1 expression in cervical carcinoma tissues and para-carcinoma tissues was inspected by real-time fluorescence quantitative PCR, and the correlation between LncRNA TDRG1 and the clinicopathological parameters and disease prognosis was analyzed. The relative expression of LncRNA TDRG1 in cervical carcinoma tissues was critically gone up (P < 0.05) compared to para-carcinoma tissues. The relative expression of LncRNA TDRG1 in cervical carcinoma was correlated with FIGO staging, lymph node metastasis, infiltrating depth of cervical basal, and the differentiation of cancer cells (P < 0.05). According to the results of the Kaplan-Meier curve and Log-rank test, the overall survival conditions of subjects with low-lncRNA TDRG1 were superior to that of those with high-lncRNA TDRG1 expression (P < 0.05). The expression of LncRNA TDRG1 in cervical carcinoma tissues and the clinicopathological features in predicting the overall survival (OS) in sufferers with cervical carcinoma were investigated by the Cox regression model. LncRNA TDRG1 expression in cervical carcinoma tissues is tightly associated with the progression and prognosis of cervical carcinoma, which may be a latent biological indicator for clinical diagnosis and prognosis of cervical carcinoma.

The pivotal role of compelling high-risk electrocardiographic markers in prediction of ventricular arrhythmic risk in arrhythmogenic right ventricular cardiomyopathy: A systematic review and meta-analysis.

INTRODUCTION: Several investigations have shown that existing risk stratification processes remain insufficient for stratifying sudden cardiac death risk in arrhythmogenic right ventricular cardiomyopathy (ARVC). Multiple auxiliary parameters are investigated to offer a more precise prognostic model. Our aim was to assess the association between several ECG markers (epsilon waves, prolonged terminal activation duration (TAD) of QRS, fragmented QRS (fQRS), late potentials on signal-averaged electrocardiogram (SA-ECG), T-wave inversion (TWI) in right precordial leads, and extension of TWI in inferior leads) with the risk of developing poor outcomes in ARVC. METHODS: A systematic literature search from several databases was conducted until September 9th, 2023. Studies were eligible if it investigated the relationship between the ECG markers with the risk of developing ventricular arrhythmic events. RESULTS: This meta-analysis encompassed 25 studies with a total of 3767 participants. Our study disclosed that epsilon waves, prolonged TAD of QRS, fQRS, late potentials on SA-ECG, TWI in right precordial leads, and extension of TWI in inferior leads were associated with the incremental risk of ventricular arrhythmias, implantable cardioverter-defibrillator shock, and sudden cardiac death, with the risk ratios ranging from 1.46 to 2.11. In addition, diagnostic test accuracy meta-analysis stipulated that the extension of TWI in inferior leads had the uppermost overall area under curve (AUC) value amidst other ECG markers apropos of our outcomes of interest. CONCLUSION: A multivariable risk assessment strategy based on the previously stated ECG markers potentially enhances the current risk stratification models in ARVC patients, especially extension of TWI in inferior leads.

Mature teratoma of liver in an adult male patient.

Teratomas are germ cell tumors occurring usually in gonadal organs. They are neoplasms composed of one or more of the three germ layers. Extragonadal teratomas are uncommonly reported in the literature. The liver is an extremely rare site for teratoma, constituting < 1% of all teratomas. The majority of the liver teratomas are found in the pediatric population with only a dozen cases reported in adults to the best of our knowledge. We present a case of a 27-year-old male with a history of abdominal pain of 5 months duration. CT scan revealed liver mass suggesting teratoma. The patient underwent cholecystectomy and segmental liver resection. Histopathology revealed mature cystic teratoma. Complete resection remains the best treatment option. Teratomas of the liver are extremely rare, constituting < 1% of all teratomas. An extensive review of the literature yielded < 50 cases of primary hepatic teratomas with only a dozen cases in adults and only two cases in males.

Does maternal health voucher scheme have association with distance inequality in maternal and newborn care utilization? Evidence from rural Bangladesh.

BACKGROUND: Bangladesh has made substantial progress in maternal health. However, persistent inequities in service use undermine the achievements at the national level. In 2007, the government introduced a Maternal Health Voucher Scheme (MHVS) to reduce barriers to service utilization. The current study explores the impact of MHVS on reducing distance inequality in utilization across the maternal and newborn continuum of care (MNCoC). METHODS: A cross-sectional survey was conducted from October'2017 to April'2018 in four selected MHVS sub-districts of Chattogram and Sylhet Divisions of Bangladesh. 2,400 women with at-least one child aged below two years were randomly selected. Both bivariate and multivariate analyses were carried out to explore the absolute and relative influence of the voucher scheme and chi-square test was used for hypothesis testing. RESULTS: Nineteen percent of the women were MHVS beneficiaries and 23% of them lived within 5 km of the health facility. Among the beneficiaries no significant differences were observed in the utilization of at-least 4 antenatal visits, skilled-assistance at delivery, postnatal care, and MNCoC between those living closer to the health facility and those living far away. However, a higher facility delivery rate was observed among beneficiary women living closer. By contrast, for non-beneficiaries, a significant difference was found in service use between women living closer to health facilities compared to those living further away. CONCLUSION: The study found the use of MNCoC to be similar for all MHVS beneficiaries irrespective of their distance to health facilities whereas non-beneficiary women living further away had lower utilization rates. MHVS could have potentially reduced distance-related inequality for its beneficiaries. However, despite the provision of transport incentives under MHVS the reduction in inequality in facility delivery was limited. We propose a revision of the transportation incentive adjusting for distance, geographical remoteness, road condition, and transport cost to enhance the impact of MHVS.

Cardiology residents' attitudes towards clinical supervision: a multi-centered study.

PURPOSE: Residents' gender, residency level, and hospital types might influence their attitudes towards clinical supervision (CS); however, reports of its impact on cardiology residency are nonexistent. We explore the effect of gender, residency level, and hospital location's effect on Indonesian cardiology trainees' attitudes towards CS. METHODS: A multi-centered, cross-sectional study was conducted. We invited 490 Indonesian cardiology residents in September- October 2019 to complete the Cardiology CS Scale. Residents' attitudes, gender, university, and residency year were expressed using descriptive statistics. A Mann-Whitney test analyzed the gender and university location effect on residents' attitudes. Training year and university's impact were subjected to the Kruskal-Wallis test; a p-value of <0.05 reflected a significant result. RESULTS: A total of 388 residents agreed to participate (response rate=79.18%). Most of them were male (n=229 [59,02%]), attended universities in Java Island (n=262 [67,52%]), and were in their 2nd-3rd year of training (n=95 [24.48%], each). There were no significant differences in residents' attitudes between genders (U [Nmale=229, Nfemale=159]=17,908.50, z=-0.27, p=0.78). Generally, their attitudes were significantly affected by the university (H(7)=47.38, p<0.01). However, the university location (located in Java Island or outside Java Island) does not affect residents' attitude towards CS (U [NJava=262, Nnon-Java=126]=15,237.00, z=-1.23, p=0.22). In addition, the residents' training year also affected the residents' response (H(2)=14.278, p<0.01). CONCLUSION: Cardiology residents' attitudes towards CS are significantly influenced by training year and university but not gender or university location. The results might provide insightful information for further improvement of CS in cardiology training and guide further evaluation.

Examining the Association Between Serotonergic Antidepressants and Blood Transfusion Requirements in Orthopaedic Surgery: A Comprehensive Analysis.

AIM: The study aimed to investigate the association between the use of serotonergic antidepressants and blood transfusion requirements in orthopedic surgical patients. METHODOLOGY: A retrospective follow-up study was conducted at Kota Trauma Hospital, Kota, Rajasthan focusing on patients who underwent orthopedic surgeries between November 2021 through December 2022. Patients were categorized into two groups: users of serotonergic antidepressants and users of other antidepressants (non-selective serotonergic antidepressants). The requirement for blood transfusion for both groups was assessed. Covariate factors, such as medication use and comorbidities (e.g., diabetes mellitus, cardiovascular diseases), were examined to control potential confounding variables. RESULT: A total of 170 subjects with complete medical records were included in the study. The results presented a significant association between the usage of serotonergic antidepressants and blood transfusion requirements (p=0.001). While no significant differences between the two groups were observed in perioperative hemoglobin levels and fluid infusion, there was a significant difference in blood loss and postoperative drainage. CONCLUSION: Serotonergic antidepressant usage was correlated with increased blood transfusion requirements in orthopedic surgery patients on antidepressants. The study underscores the importance of considering medication factors in perioperative management and highlights potential implications for patient care strategies.

Metabolic stratification of human breast tumors reveal subtypes of clinical and therapeutic relevance.

Extensive metabolic heterogeneity in breast cancers has limited the deployment of metabolic therapies. To enable patient stratification, we studied the metabolic landscape in breast cancers (∼3000 patients combined) and identified three subtypes with increasing degrees of metabolic deregulation. Subtype M1 was found to be dependent on bile-acid biosynthesis, whereas M2 showed reliance on methionine pathway, and M3 engaged fatty-acid, nucleotide, and glucose metabolism. The extent of metabolic alterations correlated strongly with tumor aggressiveness and patient outcome. This pattern was reproducible in independent datasets and using in vivo tumor metabolite data. Using machine-learning, we identified robust and generalizable signatures of metabolic subtypes in tumors and cell lines. Experimental inhibition of metabolic pathways in cell lines representing metabolic subtypes revealed subtype-specific sensitivity, therapeutically relevant drugs, and promising combination therapies. Taken together, metabolic stratification of breast cancers can thus aid in predicting patient outcome and designing precision therapies.

A critical review of sustainable application of biochar for green remediation: Research uncertainty and future directions.

Biochar, a carbon-rich material produced from the pyrolysis of organic biomass, has gained significant attention as a potential solution for sustainable green remediation practices. Several studies analyze biomass-derived biochar techniques and environmental applications, but comprehensive assessments of biochar limitations, uncertainty, and future research directions still need to be improved. This critical review aims to present a comprehensive analysis of biochar's efficacy in environmental applications, including soil, water, and air, by sequentially addressing its preparation, application, and associated challenges. The review begins by delving into the diverse methods of biochar production, highlighting their influence on physical and chemical properties. This review explores the diverse applications of biochar in remediating contaminated soil, water, and air while emphasizing its sustainability and eco-friendly characteristics. The focus is on incorporating biochar as a remediation technique for pollutant removal, sequestration, and soil improvement. The review highlights the promising results obtained from laboratory-scale experiments, field trials, and case studies, showcasing the effectiveness of biochar in mitigating contaminants and restoring ecosystems. The environmental benefits and challenges of biochar production, characterization, and application techniques are critically discussed. The potential synergistic effects of combining biochar with other remediation methods are also explored to enhance its efficacy. A rigorous analysis of the benefits and drawbacks of biochar for diverse environmental applications in terms of technical, environmental, economic, and social issues is required to support the commercialization of biochar for large-scale uses. Finally, future research directions and recommendations are presented to facilitate the development and implementation of biochar-based, sustainable green remediation strategies.

Conversion of archeological iron rust employing coconut husk lignin.

Rust powder collected from an archeological iron was evaluated by complementary analyses such as FTIR, XRD, XRF, and SEM/EDX. The analyses revealed that lepidocrocite (L) was the major component in the archeological iron. Coconut husk (CH) can be classified as a type of lignocellulosic biomass of renewable resources that are widely available, especially in coastal areas. In this research, the isolated lignin extracted from CH is being studied as a potential alternative for environmentally friendly applications. The isolated lignin from soda and organosolv pulping went through several analyses such as FTIR, NMR (13C and 2D-HSQC), and TGA analyses. The analyses showed that lignin isolated via soda pulping has superior antioxidant capabilities due to its greater phenolic-OH content compared to lignin isolated from organosolv pulping. The effects of lignin concentrations, pH, and reaction time were utilized in rust conversion studies of an archeological iron. 5 wt% of soda lignin (SL) was revealed as the ideal condition in this rust conversion study with a value of 84.21 %. The treated rust powder with 5 wt% of SL was then further gone through several complementary analyses, which revealed that the treated rust had nearly transformed into an amorphous state.

The soluble suppression of tumorigenicity 2 as a biomarker of early cardiac remodeling in bradycardia patients receiving permanent pacemaker therapy.

Aim: This study aims to evaluate: the difference of soluble suppression of tumorigenicity 2 (sST2) level, a biomarker for cardiac remodeling and echocardiography parameters value prior to and 1 month after implantation; and the association between pacemaker parameters and pacemaker mode along with delta sST2 levels. Materials & methods: This prospective cohort study enrolled all symptomatic bradycardia patients aged >18 years with preserved ejection fraction who underwent permanent pacemaker (PPM) implantation. Results: A total of 49 patients were included in this study. The sST2 level (ng/ml) were significantly different between prior and 1 month following PPM implantation (23.4 ± 28.4 vs 39.9 ± 63.7; p = 0.001). Conclusion: The early cardiac remodeling has occurred within 1 month after PPM implantation as indicated by increasing delta sST2 level.

It is widely known that pacing induced cardiomyopathy, which results from the utilization of a permanent pacemaker (PPM) within a long-term duration, will increase the risk of mortality and morbidity. Hence, early detection of the cardiac remodeling process is warranted in order to prevent this course. In this study, the soluble suppression of tumorigenicity 2 level (ng/ml), known as an indicator of cardiac remodeling, was significantly higher in 1 month following PPM implantation compared with the baseline (23.4 ± 28.4 vs 39.9 ± 63.7; p = 0.001). Thus, it denotes that early cardiac remodeling might occur earlier than expected, within 1 month following PPM implantation.

Susceptibility of Diabetic Patients to COVID-19 Infections: Clinico-Hematological and Complications Analysis.

BACKGROUND: Coronavirus disease 2019 has become a global health threat resulting in a catastrophic spread and more than 3.8 million deaths worldwide. It has been suggested that there is a negative influence of diabetes mellites (DM), which is a complex chronic disease, on COVID-19 severe outcomes. Other factors in diabetic patients may also contribute to COVID-19 disease outcomes, such as older age, obesity, hyperglycaemia, hypertension, and other chronic conditions. METHODS: A cohort study was conducted on the demographics, clinical information, and laboratory findings of the hospitalised COVID-19 with DM and non-DM patients were obtained from the medical records in King Faisal Specialist Hospital and Research Centre, Saudi Arabia. RESULTS: Among the study population, 108 patients had DM, and 433 were non-DM patients. Patients with DM were more likely to present symptoms such as fever (50.48%), anorexia (19.51%), dry cough (47.96%), shortness of breath (35.29%), chest pain (16.49%), and other symptoms. There was a significant decrease in the mean of haematological and biochemical parameters, such as haemoglobin, calcium, and alkaline phosphate in people with diabetes compared to non-diabetics and a considerable increase in other parameters, such as glucose, potassium, and cardiac troponin. CONCLUSIONS: According to the findings of this study, patients who have diabetes have a greater risk of developing more severe symptoms associated with COVID-19 disease. This could result in more patients being admitted to the intensive care unit as well as higher mortality rates.