anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
AIMS/HYPOTHESIS: Diabetic retinopathy is characterised by neuroinflammation that drives neuronal and vascular degenerative pathology, which in many individuals can lead to retinal ischaemia and neovascularisation. Infiltrating macrophages and activated retina-resident microglia have been implicated in the progression of diabetic retinopathy, although the distinct roles of these immune cells remain ill-defined. Our aim was to clarify the distinct roles of macrophages/microglia in the pathogenesis of proliferative ischaemic retinopathies.
METHODS: Murine oxygen-induced retinopathy is commonly used as a model of ischaemia-induced proliferative diabetic retinopathy (PDR). We evaluated the phenotype macrophages/microglia by immunostaining, quantitative real-time RT-PCR (qRT-PCR), flow cytometry and scRNA-seq analysis. In clinical imaging studies of diabetic retinopathy, we used optical coherence tomography (OCT) and OCT angiography.
RESULTS: Immunostaining, qRT-PCR and flow cytometry showed expression levels of M1-like macrophages/microglia markers (CD80, CD68 and nitric oxide synthase 2) and M2-like macrophages/microglia markers (CD206, CD163 and macrophage scavenger receptor 1) were upregulated in areas of retinal ischaemia and around neo-vessels, respectively. scRNA-seq analysis of the ischaemic retina revealed distinct ischaemia-related clusters of macrophages/microglia that express M1 markers as well as C-C chemokine receptor 2. Inhibition of Rho-kinase (ROCK) suppressed CCL2 expression and reduced CCR2-positive M1-like macrophages/microglia in areas of ischaemia. Furthermore, the area of retinal ischaemia was reduced by suppressing blood macrophage infiltration not only by ROCK inhibitor and monocyte chemoattractant protein-1 antibody but also by GdCl3. Clinical imaging studies of diabetic retinopathy using OCT indicated potential involvement of macrophages/microglia represented by hyperreflective foci in areas of reduced perfusion.
CONCLUSIONS/INTERPRETATION: These results collectively indicated that heterotypic macrophages/microglia differentially contribute to retinal ischaemia and neovascularisation in retinal vascular diseases including diabetic retinopathy. This adds important new information that could provide a basis for a more targeted, cell-specific therapeutic approach to prevent progression to sight-threatening PDR.
OBJECTIVE: This retrospective study assesses the influence of osteoporosis on the short-term clinical outcomes of lateral lumbar interbody fusion (LLIF) surgery in patients with lumbar degenerative diseases (LDDs), focusing on complications, pain intensity, and quality of life (QOL) improvements. The primary aim of this study is to investigate the impact of osteoporosis on the short-term clinical outcomes following LLIF surgery in LDD patients, with a particular focus on the incidence of cage subsidence (CS) and overall patient well-being postoperatively.
METHODS: A retrospective review was conducted on 73 patients who underwent LLIF for LDD. Patients were categorized into 2 groups based on osteoporosis status determined by dual-energy X-ray absorptiometry scans: those with osteoporosis (n = 20) and those without osteoporosis (n = 53). Data collection included demographics, surgical details, complications, magnetic resonance imaging analysis, pain intensity, and QOL (Japanese Orthopaedic Association Back Pain Evaluation Questionnaire).
RESULTS: The groups had no significant differences regarding operative time, estimated blood loss, and hospital stay duration. However, the incidence of CS was 40% in patients with osteoporosis, compared to 17% in nonosteoporotic patients. Despite this, significant improvements in spinal canal dimensions were observed in both groups. Both groups experienced significant reductions in pain intensity, with notable improvements in functional outcomes assessed by the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire, indicating the overall effectiveness of LLIF in enhancing patient well-being and functionality, irrespective of osteoporosis status.
CONCLUSIONS: Osteoporosis increases the risk of CS in LLIF surgery for LDD patients but does not affect short-term pain relief and QOL improvements.
En bloc resection of bladder tumor (ERBT) was first employed by Kawada T. et al. in 1997. The technique showed promising results in terms of safety and tumor staging. Development of laser surgery and emergence of the holmium (Ho:YAG) and later thulium (Tm:YAG) lasers in the 1990s enabled laser ERBT with subsequent studies demonstrating high efficacy and safety of the new techniques. Ho:YAG and Tm:YAG ERBT have distinct advantages over conventional TURBT such as the complete absence of the obturator nerve reflex and hence, lower risks of perforation or bleeding as well as a higher quality specimens for pathologic examination, due to lack of the cautery effect. Recently, a new type of thulium laser was developed - that allows to decrease the penetration depth less than 0.15 mm, which is two times less than that of Tm:YAG. Another advantage is the decreased carbonization compared to Tm:YAG due to better water absorption of laser energy. All these aspects make Tm:YAG a precise tool that may improve the resection quality resulting in better management. Data on laser ERBT of NMIBC with Tm:YAG is limited and that on Tm-fiber laser ERBT is absent altogether. The investigators hypothesized that Tm-fiber laser ERBT would result in a lower probability of adverse events and better recurrence-free survival compared to conventional TURBT.
We randomly selected the 40 pregnant women diagnosed GDM by two-step procedure based on Carpenter-Coustan criteria at this hospital. The diagnosis of GDM was confirmed if at least 2 of 4 glucose levels exceed based on Carpenter-Coustan criteria: fasting ≥ 95 mg/dL (5.3 mmol/L), 1 hour ≥ 180 mg/dL ( 10.0 mmol/L), 2 hour ≥ 155 mg/dL (8.6 mmol/L), and 3 hour ≥ 140 mg/dL (7.8 mmol/L).
Most addiction research has focused on reward- and impulsivity-related neurocircuitry. However, the impact of the withdrawal/negative affect stage in the addiction cycle has been somewhat overlooked, despite it being commonly evident in the clinic. This stage crucially drives negative reinforcement of repeated drug use and relapse, yet less is known about its neural underpinnings. How negative emotional processing is dysregulated in substance dependence is incompletely understood and may manifest differentially across the types of substances. In turn, the regions involved in negative emotional processing may show different patterns of dysregulation. Understanding how neurocircuitry involved in negative states differs across various substances may help inform new targets for treatments. Following a comprehensive literature search of studies examining negative emotional processing in substance dependence, a quantitative approach was deemed inappropriate. Instead, we employed a narrative approach to exploring neural responses to tasks involving emotional processing in alcohol, cocaine, opioid and cannabis dependence. Regions that were found to be dysregulated included the amygdala, insula, anterior cingulate, and medial prefrontal cortex. However, patterns of reactivity differed across alcohol, cocaine, opioid and cannabis dependence. Brain activation in alcohol dependence broadly appeared blunted in response to negative affective stimuli and emotional faces, whilst conversely appeared heightened in cocaine dependence. In opioid dependence, the amygdala was consistently implicated, whilst the insula, anterior cingulate, and medial prefrontal cortex were implicated in cannabis dependence. However, there was wide variability amongst the studies, with very few studies investigating opioid and cannabis dependence. These findings suggest emotional dysregulation varies according to the type of substance dependence. However, the variability in findings and lack of studies highlights the need for more research in this area. Further characterisation of emotional dysregulation in substance dependence will enable identification of treatment targets. More targeted treatments that modulate negative emotional processing could substantially improve outcomes by aiding relapse prevention.
Multiple sclerosis (MS) is the most common chronic autoimmune demyelinating and neurodegenerative disease of the central nervous system (CNS) of disabling neurological diseases in young adults in France. Patients with MS can present a wide range of symptoms spread over time and space such as motor, sensory, visual or vesico-sphincter deficits. One of the current challenges in treating patients with symptoms suggestive of MS is to assess the risk of an inflammatory flare in order to avoid or limit the installation of an irreversible neurological handicap. At present, the inflammatory activity of the disease is evaluable only by cerebral imaging (MRI). However, these examinations can not be carried out as often as necessary because of their accessibility, cost, duration and the potential deleterious effects of gadolinium accumulation. This is why a blood biomarker able to report early on the inflammatory activity of the disease would be of great help during the monitoring and treatment of patients. TWEAK (TNF-related weak inducer of apoptosis or TNFSF12) is a pro-inflammatory cytokine member of the TNF family. This cytokine is overexpressed in tissues with chronic inflammatory diseases such as MS. It is produced by monocytes / macrophages and microglial cells and can exist in soluble or membrane form.the investigators of our clinical department were the first to describe the pro-inflammatory role of TWEAK in MS. Indeed, we have demonstrated in an animal model of MS that the inhibition of TWEAK makes it possible to reduce the severity of the disease. Our recent work (manuscript submitted for publication) has also shown results from a series of 28 patients with MS suggesting that the serum TWEAK assay may be an early marker of thrust occurrence. the investigators propose to study the concentration variations of the serum soluble form of cytokine TWEAK during the first year of MS and to analyze their correlation with the occurrence of an inflammatory disease outbreak. the investigators will perform a prospective study in which 50 patients with MS in the isolated clinical syndrome stage will be included over a 12-month period. Mental Cerebral MRIs will be performed for each patient at baseline (T0), month 6, and month 12. Serum dosages of TWEAK will be performed each month for each patient for one year. Patients will also be treated with soluble TNF, the leader in the TNF family of ligands, anti-TWEAK antibodies (which may interfere with the activity and dosage of TWEAK) as well as C-reactive Protein C ( search for intercurrent infectious episode). These dosages will be correlated with the clinical evolution (appearance or not of an inflammatory flare) as well as the data of the imagery (number of lesions raised or not by the gadolinium).
The proposed research will conduct the first ever dose-determination trial of a behavioral intervention to improve engagement in HIV care, antiretroviral therapy (ART) adherence and HIV viral suppression. The trial is designed to inform the implementation of behavioral interventions, including several in CDC's Compendium of Evidence-Based Interventions. Behavioral counseling has the flexibility and reach to overcome numerous challenges to HIV care, including social, emotional, and structural barriers. However, basic questions of how to best implement and scale-up interventions remain unanswered, such as "how much intervention is needed to achieve HIV suppression in subgroups of patients facing individual and social challenges?" There are currently no dose-determination trials in the HIV behavioral intervention literature to guide implementation decisions and health service policy. In the proposed research the investigators specifically aim to: (a) determine the minimum effective dose of an evidence-based HIV treatment engagement and adherence intervention, (b) identify subgroups of patients requiring greater and fewer intervention resources to achieve and sustain viral suppression, and (c) the costs associated with intervention dose-response. Participants who are receiving ART with empirically determined low-adherence will be randomized to either: (a) the dose determination condition of weekly evidence-based behavioral self-regulation counseling until achieving HIV suppression or (b) fixed dose 5-weekly sessions of evidence-based behavioral self-regulation counseling sessions. The dose determination condition adjusts to patient needs and determines the dose to achieve optimal adherence / HIV suppression, in contrast to the fixed dose condition that does not adjust to patient response. The trial is therefore designed to determine the number of behavioral counseling intervention sessions needed to achieve and sustain HIV suppression. Once meeting criteria for adherence / viral suppressed, counseling in the dose-determination condition is suspended. In contrast, the fixed-dose condition is delivered in five prescribed sessions as disseminated by the CDC. Follow-up assessments commence for 12-months from baseline with the primary endpoint of 12-month blood plasma HIV viral load and secondary outcome of ART adherence. Response to counseling is defined by achieving viral suppression and non-response is defined by not achieving optimal adherence / viral suppression. Participants in both the dose-determination and fixed-session conditions who initially respond and rebound to unsuppressed viral load will receive additional counseling with redose-response monitored and analyzed. Longitudinal analyses will examine intervention dose for key patient subgroups and dose-response cost-effectiveness analyses to guide resource allocation and implementation decisions. This research is aimed at informing health policy makers and programmatic decisions regarding intervention implementation to increase the likelihood of sustained HIV suppression.
Methods: This 3-year prospective project will be divided into four phases: (1) Exploration of the IP-SDM needs of continuous breast cancer rehabilitation: We will interview breast cancer patients and consult breast cancer care professionals with different disciplines to understand the IP-SDM needs of breast cancer rehabilitation in each treatment period. (2) Development of communication and decision aids: An expert panel will develop a mobile application prototype of communication and decision aids. The prototype will be testes for the understandability and applicability by breast cancer patients. (3) Development of decision coaching and IP-SDM training programs: We will consult experts to develop a decision coaching training program for breast cancer patients and an IP-SDM training program for interprofessional rehabilitation team. (4) Evaluation of the effectiveness of the patient-centered continuous and interdisciplinary shared decision making approach for breast cancer rehabilitation: We will conduct a parallel-group, single-blinded randomized controlled trial and recruit 116 breast cancer patients at Taipei Medical University Hospital to evaluate the effectiveness of the IP-SDM approach.

Expected results and impacts: We expect that the patient-centered continuous and interdisciplinary shared decision making approach for breast cancer rehabilitation will effectively improve patients' IP-SDM self-efficacy, quality of IP-SDM process, patients' satisfaction with decision, concordance between preferences and the chosen options, patients' upper limb function and health-related quality of life. In the future, this IP-SDM approach will be promising to be applied to other medical institutions and other cancer populations, so as to enhance patient-centered, interprofessional and continuous practice in cancer care.
BACKGROUND: Neonatal hypoxia ischemia (HI) related brain injury is one of the major causes of learning disabilities and memory deficits in children. In both human and animal studies, female neonate brains are less susceptible to HI than male brains. Phosphorylation of the nerve growth factor receptor TrkB has been shown to provide sex-specific neuroprotection following in vivo HI in female mice in an estrogen receptor alpha (ERα)-dependent manner. However, the molecular and cellular mechanisms conferring sex-specific neonatal neuroprotection remain incompletely understood. Here, we test whether female neonatal hippocampal neurons express autonomous neuroprotective properties and assess the ability of testosterone (T) to alter this phenotype.
METHODS: We cultured sexed hippocampal neurons from ERα+/+ and ERα-/- mice and subjected them to 4 h oxygen glucose deprivation and 24 h reoxygenation (4-OGD/24-REOX). Sexed hippocampal neurons were treated either with vehicle control (VC) or the TrkB agonist 7,8-dihydroxyflavone (7,8-DHF) following in vitro ischemia. End points at 24 h REOX were TrkB phosphorylation (p-TrkB) and neuronal survival assessed by immunohistochemistry. In addition, in vitro ischemia-mediated ERα gene expression in hippocampal neurons were investigated following testosterone (T) pre-treatment and TrkB antagonist therapy via q-RTPCR. Multifactorial analysis of variance was conducted to test for significant differences between experimental conditions.
RESULTS: Under normoxic conditions, administration of 3 µM 7,8-DHF resulted an ERα-dependent increase in p-TrkB immunoexpression that was higher in female, as compared to male neurons. Following 4-OGD/24-REOX, p-TrkB expression increased 20% in both male and female ERα+/+ neurons. However, with 3 µM 7,8-DHF treatment p-TrkB expression increased further in female neurons by 2.81 ± 0.79-fold and was ERα dependent. 4-OGD/24-REOX resulted in a 56% increase in cell death, but only female cells were rescued with 3 µM 7,8-DHF, again in an ERα dependent manner. Following 4-OGD/3-REOX, ERα mRNA increased ~ 3 fold in female neurons. This increase was blocked with either the TrkB antagonist ANA-12 or pre-treatment with T. Pre-treatment with T also blocked the 7,8-DHF- dependent sex-specific neuronal survival in female neurons following 4-OGD/24-REOX.
CONCLUSIONS: OGD/REOX results in sex-dependent TrkB phosphorylation in female neurons that increases further with 7,8-DHF treatment. TrkB phosphorylation by 7,8-DHF increased ERα mRNA expression and promoted cell survival preferentially in female hippocampal neurons. The sex-dependent neuroprotective actions of 7,8-DHF were blocked by either ANA-12 or by T pre-treatment. These results are consistent with a model for a female-specific neuroprotective pathway in hippocampal neurons in response to hypoxia. The pathway is activated by 7,8-DHF, mediated by TrkB phosphorylation, dependent on ERα and blocked by pre-exposure to T.
Pyrazinamide inhibits renal excretion of urates, frequently resulting in hyperuricemia which is usually asymptomatic. If hyperuricemia is accompanied by acute gouty arthritis, pyrazinamide should be discontinued.

Pyrazinamide should be used with caution in patients with a history of diabetes mellitus, as management may be more difficult.

Primary resistance of M. tuberculosis to pyrazinamide is uncommon. In cases with known or suspected drug resistance, in vitro susceptibility tests with recent cultures of M. tuberculosis against pyrazinamide and the usual primary drugs should be performed. There are few reliable in vitro tests for pyrazinamide resistance. A reference laboratory capable of performing these studies must be employed.
Mean plasma clearance and volume of distribution for total valproate are 0.56 L/hr/1.73 m2 and 11 L/1.73 m2, respectively. Mean plasma clearance and volume of distribution for free valproate are 4.6 L/hr/1.73 m2 and 92 L/1.73 m2. Mean terminal half-life for valproate monotherapy ranged from 9 to 16 hours following oral dosing regimens of 250 mg to 1000 mg.

The estimates cited apply primarily to patients who are not taking drugs that affect hepatic metabolizing enzyme systems. For example, patients taking enzyme-inducing antiepileptic drugs (carbamazepine, phenytoin, and phenobarbital) will clear valproate more rapidly. Because of these changes in valproate clearance, monitoring of antiepileptic concentrations should be intensified whenever concomitant antiepileptics are introduced or withdrawn.
A linear dispensing system is provided that includes a plurality of channels, a pair of parallel rails, a plurality of carriers and a plurality of linear motor modules. The channels are configured to hold inventory products at an orientation. The pair of parallel rails is disposed at a bottom portion of the channels. The carriers are slidably disposed on the rails and have a conveyor unit configured to pick the inventory product from the channels while substantially maintaining the same geometric orientation as in the channel. The linear motor modules are disposed between the parallel rails and aligned end to end. The linear motor modules are coupled with the carriers and configured to pass the carriers to an adjacent linear motor module. Each carrier delivers a plurality of selected products of varying shapes to a universal escapement structure where the products are labeled, imaged, verified and dispensed.
Five optimized genes of capsid L1 protein from human papillomavirus type 16, 58, 18, 6 and 11, which are modified by using insect's preferred codons and so on. Method for modifying those genes to express more highly in insect cells. Virus-like particle's vaccine compositions comprising HPV L1 proteins or their functional relatives produced by using those modified genes. Those optimized genes of L1 can be used to produce HPV 16 VLP, HPV 58VLP, HPV 18VLP, HPV 6 VLP, HPV 11VLP in insect cells. Yields of virus-like particles derived from those optimized HPV L1 genes are high. Mixed multivalent vaccines comprising above optimized HPV L1 genes can be used to prevent and treat multiple HPV infection and diseases related with it.
Subjects will participate in a total of seven group sessions. There will be 4 or 6 subjects per group and one therapist will be assigned to each subject for a total of 4 or 6 therapists. In addition, there will be one Group Leader that will facilitate the group sessions. Group sessions will occur once per week for approximately five weeks. The first three sessions are "Preparatory" sessions followed by three "Integration" sessions. During the week following the third Preparatory session and prior to the first Integration session, participants will participate in a psilocybin session.
The prescreening study consists of genetic and visual assessments and will require at least 1 onsite visit. All clinical assessments performed are for the purpose of determining research eligibility for ACDN-01 clinical trials.
BACKGROUND AND OBJECTIVES: Malignant sweat gland tumors are rare, with the most common being eccrine porocarcinoma (EP). Approximately 18% of benign eccrine poroma (EPO) transit to EP. Previous research has provided first insights into the mutational landscape of EP. However, only few studies have performed gene expression analyses. This leaves a gap in the understanding of EP biology and potential drivers of malignant transformation from EPO to EP.
METHODS: Transcriptome profiling of 23 samples of primary EP and normal skin (NS). Findings from the EP samples were then tested in 17 samples of EPO.
RESULTS: Transcriptome profiling revealed diversity in gene expression and indicated biologically heterogeneous sub-entities as well as widespread gene downregulation in EP. Downregulated genes included CD74, NDGR1, SRRM2, CDC42, ANXA2, KFL9 and NOP53. Expression levels of CD74, NDGR1, SRRM2, ANXA2, and NOP53 showed a stepwise-reduction in expression from NS via EPO to EP, thus supporting the hypothesis that EPO represents a transitional state in EP development.
CONCLUSIONS: We demonstrated that EP is molecularly complex and that evolutionary trajectories correspond to tumor initiation and progression. Our results provide further evidence implicating the p53 axis and the EGFR pathway. Larger samples are warranted to confirm our findings.