anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Background: Gabapentinoid anticonvulsants are standard treatment for neuropathic pain and are often combined with opioids for treating cancer. It is assumed that this combination may heighten somnolence and respiratory depression due to the inhibitory effects of opioids on the central nervous system. Although pregabalin, a gabapentinoid, is known to increase somnolence frequency during opioid therapy, whether mirogabalin exerts similar effects on somnolence frequency under opioid therapy remains unknown. This study examined the signals of somnolence and respiratory depression in response to pregabalin and mirogabalin use by utilizing data from the Japanese Adverse Drug Event Report database and assessed their interaction with strong opioid analgesics. Methods: Information was obtained from the JADER database from April 2004 to August 2023 via the Pharmaceuticals and Medical Devices Agency website. The study focused on neuropathic pain medications, specifically "pregabalin" and "mirogabalin besilate." Adverse events were defined using preferred terms (PTs) from the Medical Dictionary for Regulatory Activities version 26.1. The PTs considered were "Somnolence (10041349)" and "Respiratory depression (10038678)." To investigate the effect of the combination of strong opioid analgesics with pregabalin and mirogabalin on the occurrence of somnolence, a multivariable logistic regression analysis was conducted. Results: Signals for somnolence were detected with the use of both drugs (pregabalin: information component (IC) [95% confidence intervals (CIs)]: 2.89 [2.70 to 3.08]; mirogabalin: IC [95% CIs] 2.50 [1.85 to 3.16]). When evaluating respiratory depression, a typical and serious adverse event of opioid analgesic use, a signal was detected with pregabalin use but not with mirogabalin use (pregabalin: (IC [95% CIs] 1.28 [0.83 to 1.73]; mirogabalin: IC [95% CIs] -0.15 [-2.20 to 1.89]). Multivariable analysis indicated that the use of strong opioid analgesics increased the occurrence of somnolence when combined with pregabalin but not when combined with mirogabalin (p = 0.004). Conclusion: While the safety of concomitant administation of mirogabalin with opioids remains controversial, caution should be exercised when using pregabalin, especially in combination with opioids for neuropathic pain, compared to that for mirogabalin.
Psoriasis is a chronic inflammatory skin disease characterized by excessive proliferation of keratinocytes and infiltration of immune cells. Although psoriasis has entered the era of biological treatment, there is still a need to explore more effective therapeutic targets and drugs due to the presence of resistance and adverse reactions to biologics. Remetinostat, an HDAC inhibitor, can maintain its potency within the skin with minimal systemic effects, making it a promising topical medication for treating psoriasis. But its effectiveness in treating psoriasis has not been evaluated. In this study, the topical application of remetinostat significantly improved psoriasiform inflammation in an imiquimod-induced mice model by inhibiting CD86 expression of CD11C+I-A/I-E+ dendritic cells (DCs) in the skin. Moreover, remetinostat could dampen the maturation and activation of bone marrow-derived DCs in vitro, as well as the expression of psoriasis-related inflammatory mediators by keratinocytes. In addition, remetinostat could promote keratinocyte differentiation without affecting its proliferation. Our findings demonstrate that remetinostat improves psoriasis by inhibiting the maturation and activation of DCs and the differentiation and inflammation of keratinocytes, which may facilitate the potential application of remetinostat in anti-psoriasis therapy.
FIELD: medicine. ^ SUBSTANCE: invention refers to medicine and concerns a new, earlier unknown form of ranitidine hydrochloride exhibiting properties of H2-blocker. Invention consists that the form of ranitidine is X-ray amorphous. The X-ray amorphous form is physically stable, there is also described the method for preparing said X-ray amorphous form of earlier known crystal modifications. ^ EFFECT: invention provides preparing the new X-ray amorphous form of ranitidine hydrochloride exhibiting improved specific antiulcer activity. ^ 12 cl, 1 tbl, 2 dwg
Skeletal muscle atrophy is a known risk factor for immunosuppressive conditions and for a poor prognosis in sepsis. However, its immunopathology has not been experimentally elucidated. This study investigated the effects of skeletal muscle atrophy on the immunopathology of sepsis. Male C57BL/6J mice were subjected to sciatic denervation (DN) and caecal ligation and puncture (CLP) to induce muscle atrophy or sepsis. The macrophages, myeloid-derived suppressor cells (MDSC), and T-cells in peritoneal and spleen were analysed using flow cytometry. DN-induced muscle atrophy did not affect macrophage and MDSC populations. In contrast, the percentage of cytotoxic T-lymphocyte-associated antigen (CTLA)-4+ CD4+ T-cells, programmed death (PD)-1+ CD8+ T-cells, regulatory T-cells, and the CTLA-4+ regulatory T-cells was statistically significantly higher in DN-CLP mice than in sham-CLP mice. Skeletal muscle atrophy before sepsis triggers excessive T cell immunosuppression, which may contribute to the exacerbation of sepsis under skeletal muscle atrophy.
Temporal interference (TI) stimulation is a type of low-intensity transcranial electrical stimulation with alternating current (tACS). In case of TI stimulation, 2 electric fields in kHz range are delivered to 4 electrodes, which are placed on the surface of the skull, to modulate neural oscillations.
A process for preparing a pharmaceutically-active extract of the root of a plant of the family Valerianacae, specifically, Valeriana officinalis L., is described. This process comprises the steps of adding the roots to an alcoholic extraction solvent to form a mixture, wherein the alcoholic extraction solvent comprises between approximately 50% to approximately 100% (v/v) in a remainder of water, and heating the mixture to a temperature of between approximately 70° C. to approximately 80° C. for a period of at least approximately two hours. By this process valerenic acid is obtained in the extract, and the extract has a content of valepotriates and valepotriate degradation products or derivatives that is substantially reduced with respect to the content of valepotriates in the roots, and has a content of valerenic acids that is not substantially reduced with respect to the content of valerenic acids in the roots. Also preferably, the content of volatile oils in the extract is also not substantially with respect to the content of volatile oils in the roots. A pharmaceutically-active extract of the root of a plant of the family Valerianaceae is also described. This extract is obtained by a process comprising the steps of adding the roots to an alcoholic extraction solvent to form a mixture, wherein the alcoholic extraction solvent comprises between approximately 50% (v/v) to approximately 100% (v/v) in a remainder of water, and heating the mixture to a temperature of between approximately 70° C. to approximately 80° C. for a period of at least approximately two hours. This extract may be used in the formulation of an ingestible form, preferably exhibiting sedative and/or muscle relaxant, and/or anxiolytic activity.
Oral trimethobenzamide compositions and methods for treating and controlling nausea and/or vomiting are disclosed in warm blooded animals, especially humans including children. The oral trimethobenzamide compositions and methods of the present invention are at least as effective as a 200 mg intramuscular (I.M.) trimethobenzamide HC1 injectable formulation. In addition, an oral composition containing about 300 mg of trimethobenzamide HC1 is uniquely approximately bioequivalent to a 200 mg intramuscular (I.M.) trimethobenzamide HC1 injectable formulation. The oral pediatric trimethobenzamide compositions and methods of the present invention are believed to be at least as effective as a 200 mg intramuscular (I.M.) trimethobenzamide HC1 injectable formulation when administered at a dose of about 100 mg. In addition, an oral pediatric composition containing about 120 mg of trimethobenzamide HC1 is believed to be uniquely approximately bioequivalent to a 200 mg intramuscular (I.M.) trimethobenzamide HC1 injectable formulation when administered at a dose of about 100 mg.
Human decomposition studies aim to understand the various factors influencing human decay to assess the deceased and develop postmortem interval (PMI) estimation methods. These types of studies are typically conducted through physical experiments examining the deceased; however, big data systems have the potential to transform how large-scale forensic anthropology research questions can be addressed with curated images of donors with known demographic, climatic, and postmortem historical data. This study introduces ICPUTRD (Image Cloud Platform for Use in Tagging and Research on Decomposition), a web-based software system, which enables forensic scientists to easily access, enhance (or curate), and analyze very large photographic collections documenting the longitudinal process of human decomposition. ICPUTRD, a JavaScript-based application, was designed and built through a combination of the Waterfall and Agile software development life-cycle methods and provides an image search and tagging features with a predefined nomenclature of forensic-related keywords. To evaluate the system, a user study was conducted, involving 27 participants who completed pre- and post-study surveys and three research tasks. Analysis of the study results confirmed the feasibility and practicality of ICPUTRD to facilitate aspects of forensic research and casework involving large collections of digital photographs of human decomposition. It was observed that the nomenclature lacked certain law enforcement keywords, so future work will focus on expanding it to ensure ICPUTRD is suited for all its intended users.
After a run-in phase of 2 weeks, patients will add 3 g of sodium chloride to every meal, using a NaCl tablet of 1 g. They will continue the sodium tablet for 4 weeks with a study visit every 2 weeks. A skin biopsy will be performed before the start of the augmented salt intake and after 4 weeks.
BACKGROUND: Developmental dysplasia of the hip (DDH) is one of the principal causes of secondary hip osteoarthritis, giving rise to considerable pain, impaired mobility, and a reduced quality of life. The optimal approach to managing individuals who have Crowe type IV DDH remains controversial. This study aimed to review the existing literature on the application of total hip arthroplasty (THA) as a treatment modality for Crowe type IV DDH, assessing its efficacy in addressing this severe hip deformity.
METHODS: A comprehensive search across the PubMed, Scopus, and Web of Science databases identified relevant studies. Inclusion criteria encompassed investigations reporting outcomes of THA in Crowe type IV DDH patients. Data extraction and quality assessment were performed independently by 2 reviewers. Utilizing R software, the prevalence of THA complications was analyzed through proportion analysis, employing the inverse variance method.
RESULTS: In this systematic review, a total of 74 studies were included, comprising a collective sample size of 2,829 patients (3,356 hips) diagnosed with Crowe type IV DDH. The posterior or posterolateral approach was the most commonly utilized surgical approach, followed by the lateral Hardinge and direct lateral approaches. The majority of studies have employed subtrochanteric osteotomies. Notably, post-THA, leg length discrepancy decreased, Trendelenburg sign resolved, and back pain was reduced. Patient-reported outcome measures like the Harris Hip Score improved significantly. The pooled prevalence rates of major postoperative complications were also assessed, including dislocation (7.2%), revision (8.7%), intraoperative fractures (10.5%), loosening (5.7%), nerve paralysis (5.6%), deep vein thrombosis (3.6%), infection (3.8%), heterotopic ossification grade 2 and above (6.1%), and a complicated patient rate of 11.0%.
CONCLUSIONS: Synthesizing diverse study data, an overview of THAs performance emerges, demonstrating significant enhancements in function, pain reduction, quality of life, and the correction of substantial leg length discrepancy. While THA has shown positive outcomes, instances of complications have been reported. The decision to undergo THA should involve a collaborative assessment between the surgeon and the patient, considering potential benefits and complications.
Thyroid hormones (THs) are critical regulators of muscle metabolism in both healthy and unhealthy conditions. Acting concurrently as powerful anabolic and catabolic factors, THs are endowed with a vital role in muscle mass maintenance. As a result, thyroid dysfunctions are the leading cause of a wide range of muscle pathologies, globally identified as myopathies. Whether muscle wasting is a common feature in patients with hyperthyroidism and is mainly caused by THs-dependent stimulation of muscle proteolysis, also muscle growth is often associated with hyperthyroid conditions, linked to THs-dependent stimulation of muscle protein synthesis. Noteworthy, also hypothyroid status negatively impacts on muscle physiology, causing muscle weakness and fatigue. Most of these symptoms are due to altered balance between muscle protein synthesis and breakdown. Thus, a comprehensive understanding of THs-dependent skeletal muscle protein turnover might facilitate the management of physical discomfort or weakness in conditions of thyroid disease. Herein, we describe the molecular mechanisms underlying the THs-dependent alteration of skeletal muscle structure and function associated with muscle atrophy and hypertrophy, thus providing new insights for targeted modulation of skeletal muscle dynamics.
Patients (pediatric and adults) with a diagnosis (radiological/ histopathological) of primary brain tumors registered in the neuro-oncology disease management group between January 2005 and December 2023 will be screened. Approximately 500-600 patients are expected to be eligible per year with imaging data (approximately 500 patients are treated annually with radiation in our center with available CT data for radiation planning, and another 100-200 patients having pre-operative or post-operative scans). For the above-mentioned time period, data is expected to be available from approximately 10,000 patients, which will be the upper limit of sample size for the current study.

The area of the primary tumor (or cavity and residual tumor indicating original location for post-operative data) will be segmented on CT and /or MRI as available. The peritumoral edema will be excluded from the segmented region. The segmentation will be done manually in an initial cohort of approximately 200-500 patients. Subsequently, a machine learning algorithm like a 3D U-net or deep learning-based technique will be trained on the initial data (and validated on the next 100-200 patients to assess algorithm accuracy and robustness) for rapid implementation and segmentation of the large data set. Once brain tumor regions are identified across the entire population, density maps will be generated to reciprocate the location of tumors on a quantitative scale as per age of the patient during diagnosis (age in years as continuous data and categorical data, i.e., age groups, e.g., infants, children, teens, adolescents. adults, and elderly). The generated density maps will be compared with regions of vertebrate brain regions (with openly available literature) across species with regards to the geological scale/ deep time units, e.g., in units of 10-50 million years. Similarly, the skull bony anatomy will be extracted from CT and/ or MRI data (applying techniques like window intensity thresholds without the need for segmentation). Patients with major defects in the calvarial skull from increased intracranial pressure or surgical interventions will be excluded from the analysis of calvarial anthropometry (however, it will be available for skull base anatomy assessment). The organizational patterns will be analyzed using machine learning models and other statistical models like Bayesian statistics and compared with other publicly available normal human populations without brain tumors (adjusting for age, race as applicable), fossil data of vertebrates/ hominids, non-human primates for link recognition. The density maps and anthropometric data will be compared within the entire cohort of patients with brain tumors (from the study) stratified by factors like age (as mentioned earlier), tumor location (e.g., supratentorial vs. infratentorial), tumor grade (benign vs. low grade vs high grade). The statistical analysis for density maps and anthropometry will be done by sharing anonymized data with collaborators with expertise in similar research from the Indian Statistical Institute (Geological Studies Unit and Interdisciplinary Statistical Research Unit).
The aim of the study was to examine the association between prenatal exposure to maternal Hypertensive disorder during pregnancy (HDP) on brain structure and neurocognitive functioning (NCF) in singleton children aged between 9 and 10 years using the baseline wave of the Adolescent Brain and Cognitive Development (ABCD) Study. The ABCD Study® interviewed each child (and their parents), measured NCF, and performed neuroimaging. Exposure to maternal high blood pressure (HBP) and preeclampsia or eclampsia (PE/EL) were extracted from the developmental history questionnaire. Differences in cortical thickness (CTh) and five cognitive abilities (two executive functions, working and episodic memory, processing speed, and two language abilities) between exposed and unexposed children were examined using generalized linear models. The mediating effects of CTh, birthweight, and BMI on the relationship between maternal HDP on NCF were also examined. A total of 584-children exposed to HBP, 387-children exposed to PE/EL, and 5,877 unexposed children were included in the analysis. Neither CTh nor NCF differed between the exposed and unexposed children with or without adjusting for the confounders including the child's age, sex, race, education, and birth histories. The whole-brain CTh did not mediate the relationships between HDP and NCF. However, the relationship between HDP and most of the NCF was mediated by the child's birthweight and BMI. Exposure to maternal HDP can affect their offspring's later-life cognitive abilities via low birthweight and BMI during childhood. Prospective longitudinal studies, following up from infancy, are needed to further delineate the association of HDP on children's cognitive abilities.
Diet and inflammation may contribute to the development of multiple sclerosis (MS). The aim of this systematic review and meta-analysis was to assess the association between proinflammatory diet, as estimated by the Dietary Inflammatory Index (DII®), and the likelihood of developing MS or other demyelinating autoimmune diseases. A systematic search was performed of search engines and databases (PubMed, ISI Web of Sciences, Scopus, and Embase) to identify relevant studies before 10th June 2023. The search identified 182 potential studies, from which 39 full-text articles were screened for relevance. Five articles with case-control design (n = 4,322, intervention group: 1714; control group: 2608) met the study inclusion criteria. The exposure variable was DII, with studies using two distinct models: quartile-based comparisons of DII and assessment of continuous DII. The meta-analysis of high versus low quartiles of DII with four effect sizes showed a significant association with MS/demyelinating autoimmune disease likelihood, with an odds ratio (OR) of 3.26 (95% confidence interval (CI) 1.16, 9.10). The meta-analysis of four studies with DII fit as a continuous variable showed a 31% increased likelihood of MS per unit increment; which was not statistically significant at the nominal alpha equals 0.05 (OR 1.31; 95% CI 0.95, 1.81). In conclusion, this systematic review and meta-analysis provides evidence of a positive association between higher DII scores with the likelihood of developing MS, highlighting that diet-induced inflammation could play a role in MS or other demyelinating autoimmune diseases risk.
Type 2 diabetes mellitus is a global epidemic that due to its increasing prevalence worldwide will likely become the most common debilitating health condition. Even if diabetes is primarily a metabolic disorder, it is now well established that key aspects of the pathogenesis of diabetes are associated with nervous system alterations, including deleterious chronic inflammation of neural tissues, referred here as neuroinflammation, along with different detrimental glial cell responses to stress conditions and neurodegenerative features. Moreover, diabetes resembles accelerated aging, further increasing the risk of developing age-linked neurodegenerative disorders. As such, the most common and disabling diabetic comorbidities, namely diabetic retinopathy, peripheral neuropathy, and cognitive decline, are intimately associated with neurodegeneration. As described in aging and other neurological disorders, glial cell alterations such as microglial, astrocyte, and Müller cell increased reactivity and dysfunctionality, myelin loss and Schwann cell alterations have been broadly described in diabetes in both human and animal models, where they are key contributors to chronic noxious inflammation of neural tissues within the PNS and CNS. In this review, we aim to describe in-depth the common and unique aspects underlying glial cell changes observed across the three main diabetic complications, with the goal of uncovering shared glial cells alterations and common pathological mechanisms that will enable the discovery of potential targets to limit neuroinflammation and prevent neurodegeneration in all three diabetic complications. Diabetes and its complications are already a public health concern due to its rapidly increasing incidence, and thus its health and economic impact. Hence, understanding the key role that glial cells play in the pathogenesis underlying peripheral neuropathy, retinopathy, and cognitive decline in diabetes will provide us with novel therapeutic approaches to tackle diabetic-associated neurodegeneration.