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Background and objectives: Myasthenia gravis (MG) and Guillain−Barré Syndrome (GBS) are autoimmune neuromuscular disorders that may present as neuromuscular emergencies requiring mechanical ventilation and critical care. Comparative outcomes of these disease processes, once severe enough to require mechanical ventilation, are not known. In this study, we compared the patients requiring mechanical ventilation in terms of in-hospital complications, length of stay, disability, and mortality between these two disease entities at a national level. Materials and Methods: Mechanically ventilated patients with primary diagnosis of MG (n = 6684) and GBS (n = 5834) were identified through retrospective analysis of Nationwide Inpatient Sample (NIS) database for the years 2006 to 2014. Results: Even though mechanically ventilated MG patients were older (61.0 ± 19.1 versus 54.9 ± 20.1 years) and presented with more medical comorbidities, they had lower disease severity on admission, as well as lower in-hospital complications sepsis, pneumonia, and urinary tract infections as compared with GBS patients. In the multivariate analysis, after adjusting for confounders including treatment, GBS patients had significantly higher disability (odds ratio (OR) 15.6, 95% confidence interval (CI) 10.9−22.2) and a longer length of stay (OR 3.48, 95% CI 2.22−5.48). There was no significant difference in mortality between the groups (8.45% MG vs. 10.0% GBS, p = 0.16). Conclusion: Mechanically ventilated GBS patients have higher disease severity at admission along with more in-hospital complications, length of stay, and disability compared with MG patients. Potential explanations for these findings include delay in the diagnosis, poor response to immunotherapy particularly in patients with axonal GBS variant, or longer recovery time after nerve damage.

Millions of tonnes of leftover biosolids are increasingly stockpiled every year around the globe. Biosolids are a product of the wastewater sludge treatment process. Stockpiles necessitate the use of large areas of increasingly valuable land. Biosolids have many beneficial uses and are currently utilised in agricultural and land rehabilitation applications. However, it is estimated that 30% of biosolids are unused and stockpiled. A second and seemingly unrelated environmental issue is the massive excavation of virgin soil for brick production. The annual production of 1500 billion bricks globally requires over 3.13 billion cubic metres of clay soil—equivalent to over 1000 soccer fields dug 440 m deep or to a depth greater than three times the height of the Sydney Harbour Bridge. This paper investigates and proposes a practical solution for the utilisation of the world’s excess biosolids in fired–clay bricks. The physical, chemical and mechanical properties of fired–clay bricks incorporating 25%, 20%, 15% and 10% biosolids have been tested. Bricks were produced from three different biosolids samples collected at Melbourne’s Eastern Treatment Plant (ETP 22) and the Western Treatment Plant (WTP 10 & WTP 17–29). Compressive strength testing indicated results ranging between 35.5 MPa and 12.04 MPa for the biosolids-amended bricks. Leachate analysis was conducted on the bricks before and after firing, and the results demonstrate that between 43 and 99% of the heavy metals tested were immobilised inside the fired bricks compared to the heavy metals tested in the raw mixture. All leachate concentrations were found to be insignificant for the biosolids-incorporated bricks tested in this study. Biosolids can have significantly different chemical characteristics depending on the origin of the wastewater and the treatment procedure. Suitable leachate analysis should be undertaken on biosolids and test bricks before large-scale production is approved. Scanning Electron Microscopy (SEM) images illustrate that biosolids-amended bricks have a higher porosity than the control bricks, which corresponds to the lower thermal conductivity values recorded for biosolids-amended bricks. In addition, brick firing energy demands are estimated to decrease by up to 48.6% for bricks incorporating 25% WTP 17–29 biosolids due to the higher organic content of the mixture containing biosolids. The emissions study and comparative Life Cycle Assessment results show that the incorporation of biosolids into bricks is a positive and sustainable alternative approach with respect to all environmental impacts arising from the stockpiling of biosolids and brick manufacturing. Based on the results found in this comprehensive study, this paper proposes the inclusion of a minimum of 15% biosolids content into 15% of brick production in order to completely recycle all the approximately 5 million tonnes of annual leftover biosolids production in Australia, New Zealand, the EU, the USA and Canada. This is a practical and sustainable proposal for recycling all the leftover biosolids worldwide. Utilisation of only 15% of biosolids in brick production would reduce the carbon footprint of brick manufacturing whilst satisfying all the environmental and engineering requirements for bricks.

Skeletal dysplasias are disorders associated with a generalized abnormality in the skeleton. The Gollop-Wolfgang complex (GWC) is a limb deficiency disorder and an unusual limb malformation with highly variable manifestations. Here we report an interesting case of a 5-month old male baby from India with Gollop-Wolfgang Complex showing bifurcation of the right femur, ectrodactyly of both feet, ectrodactyly of left hand, syndactyly of right hand and unusual presentation of bilateral fibular agenesis and caudal (Sacrococcygeal) agenesis. The etiology of GWC in this 5 month old male baby could possibly be attributed to spontaneous gene mutation. The clinical, radiographic findings and the unusual presentation are presented in detail.

Moyamoya is a rare idiopathic progressive vaso-occlusive disease characterized by irreversible condition of main blood vessels to the brain as they enter into the skull. We present a case of 36 year old African American female presenting to the Out Patient Clinic with headache which were on and off for 4-6 months and did not relieve on routine medical therapy. It was associated with weakness on right side for last few days. The patient was investigated with CT Angiogram, diagnosed as Moyamoya disease and operated. She has been followed up for the last 5 years and the patient has not complained of any headaches or focal neurological symptoms.

Advanced triple-negative breast cancer (TNBC) has poorer outcomes due to its aggressive behavior and restricted therapeutic options. While therapies like checkpoint inhibitors and PARP inhibitors offer some benefits, chemotherapy remains ineffective beyond the first line of treatment. Antibody–drug conjugates (ADCs) like sacituzumab govitecan-hziy (SG) represent a significant advancement. SG combines SN-38, an irinotecan derivative, with a Trop-2-targeting antibody via a pH-sensitive linking moiety, achieving a good drug:antibody ratio. In a phase I-II study involving metastatic TNBC (mTNBC) individuals, SG achieved an overall response rate of 33.3% and a median response period of 7.7 months. The phase III ASCENT trial demonstrated SG's efficacy in relapsed or refractory TNBC, improving median progression-free survival and median overall survival compared to chemotherapy. Common side effects include neutropenia, nausea, and fatigue. This article highlights the clinical potential, pharmacokinetics, safety profile, and resistance mechanisms of SG along with key ongoing clinical trials, emphasizing its role in managing refractory mTNBC, especially in third-line therapy. The review also discusses current strategies for managing adverse reactions and sequencing ADC treatments in clinical practice, along with the predicted basis of resistance. The optimal sequencing of SG relative to other ADCs, such as trastuzumab deruxtecan or T-DXd, remains an evolving question, especially as newer agents with distinct mechanisms of action and safety profiles enter the field. Further research is essential to establish evidence-based strategies for sequencing SG and addressing disease progression post-ADC therapy. [ABSTRACT FROM AUTHOR]

Currently available COVID vaccines are effective in reducing mortality and severity but do not prevent transmission of the virus or reinfection by the emerging SARS-CoV-2 variants. There is an obvious need for better and longer-lasting effective vaccines for various prevailing strains and the evolving SARS-CoV-2 virus, necessitating the development of a broad-spectrum vaccine that can be used to prevent infection by reducing both the transmission rate and re-infection. During the initial phases of SARS-CoV-2 infection, the nucleocapsid (N) protein is one of the most abundantly expressed proteins. Additionally, it has been identified as the most immunogenic protein of SARS-CoV-2. In this study, state-of-the-art bioinformatics techniques have been exploited to design novel multiple epitope vaccines using conserved regions of N proteins from prevalent strains of SARS-CoV-2 for the prediction of B- and T-cell epitopes. These epitopes were sorted based on their immunogenicity, antigenicity score, and toxicity. The most effective multi-epitope construct with possible immunogenic properties was created using epitope combinations. EAAAK, AAY, and GPGPG were used as linkers to connect epitopes. The developed vaccines have shown positive results in terms of overall population coverage and stimulation of the immune response. Potential expression of the chimeric protein construct was detected after it was cloned into the Pet28a/Cas9-cys vector for expression screening in Escherichia coli. The developed vaccine performed well in computer-based immune response simulation and covered a diverse allelic population worldwide. These computational findings are very encouraging for the further testing of our candidate vaccine, which could eventually aid in the control and prevention of SARS-CoV-2 infections globally.

We developed an innovative system that combines Natural Language Understanding (NLU), a curated knowledge base, and the efficient management of a Large Language Model (LLM) to support motivational health coaching. Using Rasa as the core framework, we enhanced it by integrating the GPT-3.5-turbo model. Users opt into reflective dialogues during conversations. When they respond to open-ended questions, their input goes directly to the GPT-3.5-turbo model, allowing for more flexible responses. To provide curated trustworthy content, we integrated a knowledge provision component that searches a PDF-based knowledge base and generates user-friendly responses using Retrieval-Augmented Generation. We tested the system in a real-world scenario by deploying it on a Nao robot in seven older adults' homes for 1–2 weeks, encouraging positive behavioral changes in some users. Our system serves as a valuable foundation for building an even more integrated, personalized system that can connect with other Application Programing Interfaces (APIs) and integrate with home sensors and edge devices. [ABSTRACT FROM AUTHOR]

For the optimal survival of a species, an organism coordinates its reproductive decisions with the nutrient availability of its niche. Thus, nutrient-sensing pathways like insulin-IGF-1 signaling (IIS) play an important role in modulating cell division, oogenesis, and reproductive aging. Lowering of the IIS leads to the activation of the downstream FOXO transcription factor (TF) DAF-16 in Caenorhabditis elegans which promotes oocyte quality and delays reproductive aging. However, less is known about how the IIS axis responds to changes in cell cycle proteins, particularly in the somatic tissues. Here, we show a new aspect of the regulation of the germline by this nutrient-sensing axis. First, we show that the canonical G1-S cyclin, Cyclin D/CYD-1, regulates reproductive fidelity from the uterine tissue of wild-type worms. Then, we show that knocking down cyd-1 in the uterine tissue of an IIS receptor mutant arrests oogenesis at the pachytene stage of meiosis-1 in a DAF-16-dependent manner. We observe activated DAF-16-dependent deterioration of the somatic gonadal tissues like the sheath cells, and transcriptional de-regulation of the sperm-to-oocyte switch genes which may be the underlying reason for the absence of oogenesis. Deleting DAF-16 releases the arrest and leads to restoration of the somatic gonad but poor-quality oocytes are produced. Together, our study reveals the unrecognized cell non-autonomous interaction of Cyclin D/CYD-1 and FOXO/DAF-16 in the regulation of oogenesis and reproductive fidelity. Author summary: The conserved insulin-IGF-1 signaling (IIS) pathway in Caenorhabditis elegans is a neuroendocrine cascade that surveils the availability of nutrients as well as exposure to environmental and cellular stressors to regulate somatic development, reproduction and aging, both cell autonomously and non-autonomously. Lowering IIS flux activates the downstream FOXO transcription factor DAF-16 that mediates most of these responses. How this pathway responds to perturbations in cell cycle proteins to influence reproductive decision is less known. Here we show that the G1-S phase cyclin, Cyclin D/CYD-1 and the IIS nutrient-sensing axis crosstalk to regulate oogenesis and germ cell quality. In the wild-type worms, we found that CYD-1 in the uterine tissue regulates oocyte health and reproductive fidelity. Knocking down cyd-1, only in the somatic uterine tissue of IIS mutants, leads to a DAF-16-dependent arrest of oogenesis. Interestingly, we observed DAF-16-dependent destruction of the somatic gonadal tissues and de-regulation of the sperm-to-oocyte switch genes when CYD-1 is depleted in the uterus of animals with lower IIS. We speculate that defects in cell cycle proteins in the uterus may be interpreted by activated DAF-16 as a potential threat to progeny health that is unlikely to be rectified. So, our study unveils a new function of activated FOXO/DAF-16 and Cyclin D/CYD-1 in maintaining oocyte health and reproductive fidelity. [ABSTRACT FROM AUTHOR]

Since life expectancy has increased significantly over the past century, society is being forced to discover innovative ways to support active aging and elderly care. The e-VITA project, which receives funding from both the European Union and Japan, is built on a cutting edge method of virtual coaching that focuses on the key areas of active and healthy aging. The requirements for the virtual coach were ascertained through a process of participatory design in workshops, focus groups, and living laboratories in Germany, France, Italy, and Japan. Several use cases were then chosen for development utilising the open-source Rasa framework. The system uses common representations such as Knowledge Bases and Knowledge Graphs to enable the integration of context, subject expertise, and multimodal data, and is available in English, German, French, Italian, and Japanese.

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder, which has complex diagnostic steps. Electrochemical immunoassays may make the diagnosis simpler and faster. Here, we present the detection of ALS-associated neurofilament light chain (Nf-L) protein through an electrochemical impedance immunoassay on reduced graphene oxide (rGO) screen-printed electrodes. The immunoassay was developed in two different media, i.e., buffer and human serum, to compare the effect of the media on their figures of merit and calibration models. The label-free charge transfer resistance (RCT) of the immunoplatform was used as a signal response to develop the calibration models. We found that exposure of the biorecognition layer to human serum improved the impedance response of the biorecognition element with significantly lower relative error. Moreover, the calibration model obtained in the human serum environment has higher sensitivity and a better limit of detection (0.087 ng/mL) than the buffer medium (0.39 ng/mL). The analyses of the ALS patient samples show that concentrations obtained from the buffer-based regression model was higher than the serum-based model. However, a high Pearson correlation (r = 1.00) between the media suggests that concentration in one medium may be useful to predict the concentration in the other medium. Moreover, the Nf-L concentration appears to increase with age in both male and female groups, while overall higher Nf-L was found in the male group than the female group.