anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Malaria caused by Plasmodium falciparum continues to be a global problem with devastating consequences. Pregnancy malaria is associated with low birth weight, maternal anemia, and gestational hypertension, and both inflammation and the fetal response to infection may contribute to these poor outcomes. Pregnancy malaria is caused by P. falciparum-infected erythrocytes that bind to the placental receptor chondroitin sulfate A (CSA) and sequester in the placenta, where they cause disease and death for the mother and her offspring. Women become resistant to pregnancy malaria as they acquire antibodies that target surface proteins of placental parasites. Malaria vaccine candidates targeting the parasite s liver stage or blood stage may not protect pregnant women and their unborn children. The primary hypothesis in this study is that antibodies raised in animals against recombinant pregnancy malaria vaccine candidates will have a similar functional activity as naturally acquired antibodies. Up to 1500 pregnant women will be recruited into a cross sectional study that will be conducted in Rakai, Uganda. Women presenting for delivery and their newborns and women presenting for antenatal visit at Kalisizo Hospital, Rakai District will be enrolled. Samples collected from the women will be used in in-vitro assays to assess the functional activity of antisera raised against pregnancy malaria vaccine candidates as the primary outcome of this study. For our secondary outcomes, we will examine various factors that can lead to poor outcomes such as low birth weight of infants by measuring newborns for birth weight and physical and muscular maturity using the Dubowitz Ballard Exam for Gestational Age. We will also study the effects of intermittent preventive therapy during pregnancy (IPTp) on immune responses in the mother as well as the effect of HIV infection on the acquisition of immunity to pregnancy malaria. Clinical, parasitological and host response endpoints (including naturally acquired functional antibodies against CSA-binding parasites) will be analyzed using appropriate statistical methods, including adjustment for possible confounders, to determine factors associated with malaria infection and disease in pregnant women, as well as pregnancy outcomes.
Bone is one of the most frequently targeted organs in metastatic cancers including the breast. Breast cancer bone metastasis often results in devastating outcomes as limited treatment options are currently available. Therefore, innovative methods are needed to provide earlier detection and thus better treatment and prognosis. Here, we present a new approach to model bone-like microenvironments to detect invasion and extravasation of breast cancer cells using invasion/chemotaxis (IC-) and extravasation (EX-) chips, respectively. Our results show that the behaviors of MDA-MB-231 breast cancer cells on IC- and EX-chip models correlate with their in vivo metastatic potential. Our culture model constitutes cell lines representing osteoblasts, bone marrow stromal cells, and monocytes embedded in three-dimensional (3D) collagen I-based extracellular matrices of varying composition and stiffness. We show that collagen I offers a better bone-like environment for bone cells and matrix composition and stiffness regulate the invasion of breast cancer cells. Using in situ contactless rheological measurements under cell culture conditions, we show that the presence of cells increased the stiffness values of the matrices up to 1200 Pa when monitored for five days. This suggests that the cellular composition has a significant effect on regulating matrix mechanical properties, which in turn contribute to the invasiveness. The platforms we present here enable the investigation of the underlying molecular mechanisms in breast cancer bone metastasis and provide the groundwork of developing preclinical tools for the prediction of bone metastasis risk.
A major challenge for future health care is the care for dementia patients and their informal caregivers. In usual care, the problems of caregivers often remain invisible until a crisis occurs. This inhibition is partly the result of informal caregivers paying scant attention to their own problems. Another reason is that professionals may not know how to support informal caregivers pro-actively (Van Hout et al., 2000). Therefore the family support programme (Bengtson, 1985: Vernooij et al., 2000) has been transformed into a Systematic Care Programme (SCP-Dementia). The reasons for choosing and studying the efficiency of this programme are the potential to diagnose and treat problems systematically, to cover a wide range of individual problems, its flexibility in connecting interventions to these problems, its suitability for pro-activity and the positive effects of the programme found in our previous study (Vernooij et al., 2000). To study its efficiency a cluster randomised controlled trial design will be used. Randomisation will take place in each of three participating regions. Professionals in the ambulatory mental health care services (psychologists and social psychiatric nurses) will be randomly assigned to either the intervention group or the control group before the recruitment of patients and informal caregivers. The study population consists of pairs of patients and their informal caregivers visiting the ambulatory mental health care service for the first time. The intervention is the training in SCP-Dementia and its subsequent use. SCP-Dementia consists of an assessment of the caregiver's sense of competence and suggestions on how to deal with deficiencies in competence. The follow-up period is one year. The primary outcome is patients´ admissions to nursing homes or residential homes. The secondary outcome is quality of life. Caregivers´ quality of life is assessed by sense of competence (SCQ), depression (CES-D) and physical quality of life (EuroQol). Patients´ quality of life by behavioral problems is assessed by the NPI-Q and the QOL-AD-Scale. The difference in proposed effect was based on previous research in which 14% of the patients in the intervention group and 28% in the control group were institutionalized (Vernooij-Dassen, 1993;1995). To detect a 50% reduction in institutionalization rates with 80% power at the two sided significance level of 0.05, 132 patient-caregiver dyads would be needed for each of the intervention and control arm. We inflated this sample size by a design effect of 1.15 to 152 dyads per trial arm to allow for correlation of dyads within the same cluster (i.e. professional), assuming an average cluster size of four and an intracluster correlation coefficient of 0.05. Assuming a 25% dropout rate of patient-caregiver dyads, the study needed an final enrolment of 190 dyads in each trial arm. The economic evaluation is a cost-effectiveness analysis regarding a societal perspective. In the economic evaluation both costs and effects will be monetarized and consequently will result in a net benefit.
HAIR CONDITIONING PRODUCT                 James H. Donovan Abstract of the Disclosure Hair conditioning products and methods.  Hair con-ditioning agents, such as ditallow dimethylammonium chloride, are releasably affixed to one surface of a substrate.  The substrate, which must be flexible, impervious, and nonabsorbent, is provided with a backing sheet.  In use, the product is passed over and through the hair so that the hair conditioning agent is trans-ferred from the product to the hair.  Preferably, the hair has been shampooed and is still damp at the time the product is used.  After it has been treated with the product, the hair is easier to comb and detangle when wet and exhibits, when dry, enhanced softness, luster, and manageability.
A system and method for uniquely identifying data streams associated with medical equipment are described. The system may be implemented in a variety of ways, including as a combination of a medical device (120), a data stream identifier (204), and a medical device identifier (206). The medical device (120) generates a plurality of data streams. The data streams are uninterrupted transmissions of data from the medical device (120). The data streams include information regarding the operation of the medical device (120). The data stream identifier (204) attaches a unique data tag to the da ta streams. The medical device identifier (206) is configured to generate a medical device tag. The medical device tag includes information to uniquely identify the medical device (120) and is accessible from an external compute r (108). The data stream identifier (204) and the medical device identifier (206) are secured to the medical device.
BACKGROUND: Heart failure with reduced (HFrEF) or preserved ejection fraction (HFpEF) is characterized by low-grade chronic inflammation. Circulating neutrophils regroup 2 subtypes termed high- and low-density neutrophils (HDNs and LDNs). LDNs represent less than 2% of total neutrophil under physiological conditions, but their counts increase in multiple pathologies, releasing more inflammatory cytokines and neutrophil extracellular traps (NETs). The aims of this study were to assess the differential count and role of HDNs, LDNs, and NETs-related activities in patients with heart failure (HF).
METHODS: HDNs and LDNs were isolated from human blood by density gradient and purified by fluorescence-activated cell sorting (FACS) and their counts obtained by flow cytometry. Formation of NETs (NETosis) was quantified by confocal microscopy. Circulating inflammatory and NETosis biomarkers were measured by enzyme-linked immunosorbent assay (ELISA). Neutrophil adhesion onto human extracellular matrix (hECM) was assessed by optical microscopy.
RESULTS: A total of 140 individuals were enrolled, including 33 healthy volunteers (HVs), 41 HFrEF (19 stable patients and 22 presenting acute decompensated HF [ADHF]), and 66 patients with HFpEF (36 stable patients and 30 presenting HF decompensation). HDNs and LDNs counts were significantly increased up to 39% and 2740%, respectively, in patients with HF compared with HVs. In patients with HF, the correlations among LDNs counts and circulating inflammatory (CRP, IL-6 and -8), troponin T, N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and NETosis components were significant. In vitro, LDNs expressed more citrullinated histone H3 (H3Cit) and NETs and were more proadhesive, with ADHFpEF patients presenting the highest proinflammatory profile.
CONCLUSIONS: Patients with HFpEF present higher levels of circulating LDNs- and NETs-related activities, which are the highest in the context of acute HF decompensation.
BACKGROUND: Parathyroidectomy has been shown to be superior to medical management in treating hypercalcemia and preserving renal allograft function in patients with tertiary hyperparathyroidism after kidney transplant. Despite this evidence, parathyroidectomy remains underused. We aimed to evaluate outcomes in patients with tertiary hyperparathyroidism after kidney transplant based on management strategy (cinacalcet or parathyroidectomy) and optimal timing of parathyroidectomy.
METHODS: Data from TriNetX Dataworks included adult kidney transplant patients diagnosed with tertiary hyperparathyroidism between 1998 and 2021. Patients who underwent parathyroidectomy were compared with those receiving cinacalcet. Subgroups based on parathyroidectomy timing after transplant were analyzed (within 6 months, 6 months to 1 year, and between 1 and 3 years). Descriptive statistics and relative risks were calculated using TriNetX Live.
RESULTS: Patients receiving cinacalcet (n = 162) had a 77% higher risk of persistent hypercalcemia and a 73% higher risk of elevated parathyroid hormone levels than those who underwent parathyroidectomy (n = 338) within 3-10 years after the index event (start of cinacalcet or surgery). Parathyroidectomy performed 1 year after transplant (n = 132) was associated with a 57% lower risk of kidney stone formation and patients were 2 times more likely to maintain normal glomerular filtration rate than parathyroidectomy performed 1-3 years after transplant (n = 57). Even earlier parathyroidectomy (within 6 months of kidney transplant, n = 55) showed a 62% lower risk of persistent hypercalcemia, hyperphosphatemia, and kidney stone formation than surgery between 6 months and 1 year after transplant (n = 77).
CONCLUSION: Parathyroidectomy is more effective than cinacalcet in managing tertiary hyperparathyroidism after kidney transplant. In addition, opting for early parathyroidectomy (within 6 months after transplant) could enhance long-term outcomes.
BACKGROUND: Ferroptosis is a distinct form of cell death characterized by unique morphology, biochemistry, and genetics, playing a crucial role in the initiation, progression, prognosis, and therapeutic strategies of tumors. However, the impact of ferroptosis-related genes (FRGs) on the tumor microenvironment (TME) remains unclear. This study may advance the existing knowledge of FRGs in gastric cancer, and push ahead with more effective prognostic assessment and the development of more effective immunotherapy approaches.
METHODS: FRGs were acquired from the FerrDb database and a consensus clustering technique was adopted to categorize patients with GC into groups in line with the expression profiles of 44 FRGs in order to further investigate the expression properties of these proteins. Assessment of the immune status, microsatellite instability (MSI) and cancer stem cell (CSC) index between the high- and low- risk groups to assess the proportion of TIICs in the TME, ssGSVA was adopted to detect the abundance of infiltrating immune cells from the low-risk and high-risk groups. Expression levels of eight ferroptosis-related genes of prognostic signature in GC tissues and adjacent normal tissues was detected by RT-PCR.
RESULTS: In the GC cohort, TP53 has the highest mutation frequency (44 %), and was shown to be highly linked with the expression levels of 11 FRGs. In accordance with the Kaplan-Meier curve, the overall survival time of patients with subtype A (Low FRG-score) discernibly exceeded that of patients with subtype B (High FRG-score).In addition, there is a significant difference in the infiltration of most immune cells between subtype A and subtype B, and some important immune checkpoints (CTLA4, PDCD1, CD274, LAG3, PDCD1LG2, and HAVCR2) have higher expression in cluster A. Finally, low FRG-scores were significantly associated with MSI-H status, while high FRG-scores were significantly associated with microsatellite stable status (MSS). FRG-score is negatively related to the cancer stem cell (CSC).
CONCLUSION: Low FRG-score, due to its high microsatellite instability (MSI-H), high mutational load and immune activation, indicates the possible advantage of OS. In addition, the FRG-score was closely related to the cancer stem cell (CSC) index and the sensitive degree of chemotherapeutic drug.
Accessible, usable, and effective vaginal microbicides could significantly decrease the spread of HIV. Vaginal microbicides could be used with condoms to prevent HIV infection; they could also be used in situations in which an individual is unable to negotiate condom use. Vaginal microbicides are potentially bidirectional, preventing both male-to-female and female-to-male HIV transmission. This study will evaluate the safety and effectiveness of two vaginal microbicides, BufferGel and PRO 2000/5, in preventing the transmission of HIV. The study will also evaluate the effectiveness of these gels in preventing other common sexually transmitted infections (STIs).

BufferGel is a buffering agent designed to maintain normal vaginal acidity in the presence of ejaculate. Studies have shown that HIV is inactivated below a pH of 4 to 5.8. Carbopol 974, the major nonaqueous component of BufferGel, is commonly used as a gelling or tableting agent and has a well-documented safety record. BufferGel has proven safe and well tolerated in Phase I studies. PRO 2000/5 inhibits viral entry into susceptible cells. PRO 2000/5 has also been evaluated in Phase I studies and was found to be safe and well tolerated.

Participants in this study will be randomly assigned to receive one of four interventions: BufferGel, PRO 2000/5, placebo gel, or no gel. All participants will receive HIV risk reduction counseling, condoms, and diagnosis and treatment of sexually transmitted diseases. Participants in the three gel arms will be given single-use, prefilled applicators of gel and will be instructed to apply one dose of the product (BufferGel, PRO 2000/5, or placebo gel) intravaginally up to 60 minutes before each vaginal intercourse while in the study.

Participants will be enrolled for approximately 12 to 30 months, depending on when they enter the study. Participants will have two screening study visits and then monthly visits. Monthly study visits may take place at a clinic, the participant's home, or other community site. Monthly visits will include a medical interview; urine testing, including pregnancy testing; HIV and sexually transmitted infection risk reduction counseling; and distribution of study supplies (condoms and gel-filled applicators). Blood collection will occur at selected monthly visits. Four times a year, participants will be seen in the clinic for a more structured medical interview, pelvic exam, and HIV testing. At one of these visits, participants at particular sites who are willing will be asked to complete a behavioral risk assessment. At some visits vaginal fluid swabs will occur. Participants at non-US study sites will be asked for permission for these swabs to be stored for further testing. Assessment interviews will be both face to face and self-reporting.
No dose adjustment is necessary in patients with mild to moderate renal impairment (CLCR ≥30 mL/min). In patients with severe renal impairment (CLCR <30 mL/min as estimated by the Cockcroft-Gault equation for adults; CLCR <30 mL/min/1.73m2 as estimated by the Schwartz equation for pediatric patients) and in those with end-stage renal disease, a reduction of 25% of the maximum dosage is recommended [see Dosage and Administration (Error! Hyperlink reference not valid.) and Clinical Pharmacology (12.3)].

In all patients with renal impairment, dose initiation and titration should be based on clinical response and tolerability.

Lacosamide is effectively removed from plasma by hemodialysis. Dosage supplementation of up to 50% following hemodialysis should be considered.
Capsular contracture, a significant complication of breast-implant surgery, causes pain and deformation following the formation of a tight capsule around an implant. Current surgical and non-surgical treatment options are invasive, expensive, and typically administered for prolonged periods, potentially leading to side effects. To address these challenges, we developed a novel fish oil-encapsulated, poloxamer-based nanoemulsion gel with omega-3 (ω3) as the primary active component (NE-ω3 gel; N3G). This formulation can be injected during surgery, reducing the need for prolonged administration of medications and minimizing associated side effects. N3G was prepared through a two-step process involving the emulsification of fish oil followed by gelation with poloxamer to create a thermoreversible gel. Dynamic light-scattering analysis confirmed a uniform distribution of nanoemulsion particles, which had a mean diameter of 287 ± 8.599 nm and a PDI of 0.29 ± 0.047. FTIR and DSC analyses validated the encapsulation of fish oil within poloxamer micelles. Drug-release analysis demonstrated that more than 96% of fish oil was released within 10 h. In in vivo experiments, rats (n = 30) were divided into three groups: a negative control group (G1), a positive control group receiving fish oil (G2), and an experimental group with implants coated with N3G (G3). G3 exhibited a 21.2% reduction in capsular thickness compared to G1 and a 5.6% reduction compared to G2. In addition, significant decreases in fibrosis and myofibroblast counts were observed in G3. These results, supported by histological and gene expression analyses, highlight the effectiveness of N3G in reducing inflammation and fibrosis. This study underscores the therapeutic potential of N3G for capsular contracture, based on its persistence, thermoreversibility, and improved dosing and storage characteristics.
Liver fibrosis is characterized by the excessive accumulation of extracellular matrix proteins, which can lead to cirrhosis and liver cancer. Metabolic dysfunction-associated steatosis liver diseases are common causes of liver fibrosis, sharing a similar pathogenesis with carbon tetrachloride (CCl₄) exposure. This process involves the activation of hepatic stellate cells (HSCs) into myofibroblasts. However, the detailed mechanism and effective treatment strategies require further investigation. In this study, we uncovered a negative correlation between VDR expression and YAP within HSCs. Subsequently, we demonstrated that VDR exerted a downregulatory influence on YAP transcriptional activity in HSCs. Intriguingly, activation VDR effectively inhibited the culture induced activation of primary HSCs by suppressing the transcriptional activity of early YAP. Furthermore, in vivo results manifested that hepatic-specific deletion of YAP/TAZ ameliorates CCl4-induced liver fibrosis, and nullified the antifibrotic efficacy of VDR. Importantly, a YAP inhibitor rescued the exacerbation of liver fibrosis induced by hepatic-specific VDR knockout. Moreover, the combined pharmacological of VDR agonist and YAP inhibitor demonstrated a synergistic effect in diminishing CCl4-induced liver fibrosis, primary HSCs activation and hepatic injury in vivo. These effects were underpinned by their collective ability to inhibit HSC activation through AMPK activation, consequently curbing ATP synthesis and HSCs proliferation. In conclusion, our results not only revealed the inhibition of VDR on YAP-activated liver stellate cells but also identified a synergistic effect of VDR agonist and YAP inhibitor in an AMPKα-dependent manner, providing a practical foundation for integration of multi-targeted drugs in the therapy of CCl4-induced hepatic fibrosis.
ETHNOPHARMACOLOGICAL RELEVANCE: Piper methysticum G. Forst (Piperaceae) is traditionally consumed in Polynesian culture. The roots are used to produce an entheogenic drink and traditional medicine with sedative and anxiolytic properties. There is also evidence that it functions as a pain reliever. Kavalactones, its main active ingredients, exhibit psychoactive effects on the central nervous system. However, the active ingredients and pharmacological mechanisms underlying the analgesic effect of kavalactones are unclear.
AIM OF THE STUDY: This study investigated the effects of kavain and yangonin on nociception, inflammatory hyperalgesia, and neuropathic mechanical allodynia at the spinal level.
MATERIALS AND METHODS: Male Sprague-Dawley rats were administered kavain and yangonin (27.14 and 19.36 nmol/rat) via intrathecal injection. Tail-flick tests were performed to evaluate the anti-nociceptive properties. The efficacy of kavain and yangonin on inflammatory hyperalgesia was examined using a plantar test in rats with carrageenan-induced paw inflammation. The von Frey test was used to assess mechanical allodynia induced by partial sciatic nerve ligation.
RESULTS: Intrathecal injection of yangonin demonstrated a relatively potent anti-nociceptive effect and attenuated carrageenan-induced hyperalgesia. These effects were completely reversed by the co-administration of PF 514273, a cannabinoid 1 (CB1) receptor antagonist. However, yangonin did not affect mechanical allodynia at the spinal level. Kavain, another abundant kavalactone, did not affect nociception, hyperalgesia, or mechanical allodynia at the spinal level.
CONCLUSIONS: Overall, our study demonstrated that yangonin exerts anti-nociception and anti-inflammatory hyperalgesia effects via CB1 receptors at the spinal level. We identified a single kavalactone, yangonin, extracted from kava as a promising treatment for pain.