anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
The novel positively charged pro-drugs of oxicams and related compounds of the general formula (1) 'Structure 1' were designed and synthesized. The positively charged amino groups of these pro-drugs not only greatly increase the solubility of the drugs, but also bond to the negative charge on the phosphate head group of membranes and push the pro-drug into the cytosol. The results indicate that the pro-drugs permeate human skin approximately 100 times faster than oxicams and related compounds. Plasma drug concentrations peak 1-2 hours after oral administration of oxicams and related compounds, whereas these pro-drugs require only about 50 minutes to reach peak plasma drug concentrations upon transdermal administration. In plasma, more than 90% of the pro-drugs can return to the parent drug structure within a few minutes. These prodrugs can be used to treat any oxicams-treatable conditions in humans or animals. Second, the prodrug can be administered not only orally but also transdermally for any kind of medical treatments and avoids most of the side effects of oxicams. Controlled transdermal administration systems of these pro-drugs can stabilize the concentration of oxicams and related compounds in the blood at optimal therapeutic blood levels, enhance therapeutic efficacy and reduce the side effects of oxicams and related compounds. Another great benefit of transdermal administration of these prodrugs is that administration is more convenient, particularly to children.
OBJECTIVE: To investigate the independent risk variables associated with the potential invasiveness of ductal carcinoma in situ (DCIS) on multi-parametric ultrasonography, and further construct a nomogram for risk assessment.
METHODS: Consecutive patients from January 2017 to December 2022 who were suspected of having ductal carcinoma in situ (DCIS) based on magnetic resonance imaging or mammography were prospectively enrolled. Histopathological findings after surgical resection served as the gold standard. Grayscale ultrasound, Doppler ultrasound, shear wave elastography (SWE), and contrast-enhanced ultrasound (CEUS) examinations were preoperative performed. Binary logistic regression was used for multifactorial analysis to identify independent risk factors from multi-parametric ultrasonography. The correlation between independent risk factors and pathological prognostic markers was analyzed. The predictive efficacy of DCIS associated with invasiveness was assessed by logistic analysis, and a nomogram was established.
RESULTS: A total of 250 DCIS lesions were enrolled from 249 patients, comprising 85 pure DCIS and 165 DCIS with invasion (DCIS-IDC), of which 41 exhibited micro-invasion. The multivariate analysis identified independent risk factors for DCIS with invasion on multi-parametric ultrasonography, including image size (>2cm), Doppler ultrasound RI (≥0.72), SWE's Emax (≥66.4 kPa), hyper-enhancement, centripetal enhancement, increased surrounding vessel, and no contrast agent retention on CEUS. These factors correlated with histological grade, Ki-67, and human epidermal growth factor receptor 2 (HER2) (P < 0.1). The multi-parametric ultrasound approach demonstrated good predictive performance (sensitivity 89.7 %, specificity 73.8 %, AUC 0.903), surpassing single US modality or combinations with SWE or CEUS modalities. Utilizing these factors, a predictive nomogram achieved a respectable performance (AUC of 0.889) for predicting DCIS with invasion. Additionally, a separate nomogram for predicting DCIS with micro-invasion, incorporating independent risk factors such as RI (≥0.72), SWE's Emax (≥65.2 kPa), and centripetal enhancement, demonstrated an AUC of 0.867.
CONCLUSION: Multi-parametric ultrasonography demonstrates good discriminatory ability in predicting both DCIS with invasion and micro-invasion through the analysis of lesion morphology, stiffness, neovascular architecture, and perfusion. The use of a nomogram based on ultrasonographic images offers an intuitive and effective method for assessing the risk of invasion in DCIS. Although the nomogram is not currently considered a clinically applicable diagnostic tool due to its AUC being below the threshold of 0.9, further research and development are anticipated to yield positive outcomes and enhance its viability for clinical utilization.
The invention discloses a siRNA drug carrier. An active component of the siRNA drug carrier is a nano-particle with positive charge formed by polymer which can be polyethylene glycol monomethyl ether-polycaprolactone-polyphosphate ester tri-block copolymer concretely. The invention also provides a polyethylene glycol monomethyl ether-polycaprolactone-polyphosphate ester copolymer and a method for synthesizing the copolymer. The biocompatible tri-block copolymer provided by the invention forms the nano-particles by self-assembly in aqueous solution and has good stability, simple preparation method and high repeatability. The polymer nano-particle is used as a carrier which can protect siRNA from degrading and can also combine with the self size effect of the nano-particle. Nano-micelle has good biocompatibility, and macromolecular micelle has the characteristics of very good stability, convenient preparation and the like, thereby ensuring the biodegradable nano-micelle has good application prospect in siRNA delivery and disease treatment based on RNA interference.
AIM: Rectal cancers requiring beyond total mesorectal excision (bTME) are traditionally operated using an open approach, but the use of minimally invasive robot-assisted procedures is increasing. Introduction of minimal invasive surgery for complex cancer cases could be associated with compromised surgical margins or increased complication rates. Therefore, reporting results both clinical and oncological in large series is important. Since bTME procedure reports are heterogeneous, comparing results is often difficult. In this study, a magnetic resonance imaging (MRI) classification system was used to describe the bTME surgery according to pelvic compartments.
METHODS: Consecutive patients with primary rectal cancer operated with laparoscopic robot-assisted bTME were prospectively included for 2 years. All patients had tumors that threatened the mesorectal fascia, invaded adjacent organs, and/or involved metastatic pelvic lateral lymph nodes. Short-term clinical outcomes and oncological specimen quality were registered. Surgery was classified according to pelvic compartments resected.
RESULTS: Clear resection margins (R0 resection) were achieved in 95 out of 105 patients (90.5%). About 26% had Accordion Severity Grading System of Surgical Complications grade 3-4 complications and 15% required re-operations. About 7% were converted to open surgery. The number of compartments resected ranged from one to the maximum seven, with 83% having two or three compartments resected. All 10 R1 resections occurred in the lateral and posterior compartments.
CONCLUSIONS: The short-term clinical outcomes and oncological specimen quality after robot-assisted bTME surgery were comparable to previously published open bTME surgery. The description of surgical procedures using the Royal Marsden MRI compartment classification was feasible.
A prior clinical gene transfer study of intrahepatic adeno-associated virus (AAV) vector administration of the factor IX gene (AAV2-hFIX16) to adult subjects with severe hemophilia B enrolled several subjects from 2001 through 2004. These subjects received various doses of AAV2-hFIX16 manufactured by Avigen, Inc. (Alameda, CA). They were monitored up to at least one year following vector administration for evaluation of adverse events and for indices of efficacy. At the time study enrollment was suspended by Avigen, Inc., and IND 9398 under which the study was conducted was transferred to The Children's Hospital of Philadelphia (May 2005), there were no guidelines for long-term follow-up of the trial subjects. However, in an unrelated study conducted in France, of pediatric subjects administered integrating retrovirus vectors for X-linked severe combined immune deficiency (X-SCID), several leukemias developed years after transfer of the γc common chain gene. The underlying mechanism was attributed to proviral integration near, and upregulation of, proto-oncogenes such as LMO-2, coupled with robust expression of the γc common chain, inducing unregulated cellular proliferation. In response to these events, and in concert with the NIH and gene transfer scientific community, the U.S. Food and Drug Administration (US FDA) issued guidelines for the 'long-term follow-up of gene transfer subjects'. Since AAV vectors have a low rate of genomic integration, the risks of integration are low, but the long-term effect of the persistence of vector particles in humans is unknown. The investigators plan to enroll available subjects from the prior intrahepatic AAV gene transfer study to this observational study to follow them for up to 15 years after gene transfer.

An additional subject received AAV2-hFIX16 vector, manufactured by CCMT at CHOP, via hepatic artery infusion in January 2009. The study AAV2-hFIX-002, an amendment to the prior Avigen, Inc. clinical protocol modified to include transient immunomodulation, was conducted under IND 9398. This subject was monitored for three years following vector administration under clinical study AAV2-hFIX-002; amendment one of the current protocol transfers his annual long-term follow-up visits to AAV2-hFIX16-LTFU-01.

Spark Therapeutics will be the study sponsor; prior vector administration sites or referral/follow up sites will participate as study sites. The long-term follow-up (LTFU) study will consist primarily of endpoints including annual history, physical examination, blood tests, urinalysis, and periodic liver ultrasound. Adverse event reporting will focus on the development of oncologic, hematologic, neurologic and auto-immune events following gene transfer as specified in the November 2006 FDA Center for Biologics Evaluation and Research (CBER) guidance document entitled, "Gene Therapy Clinical Trials - Observing Subjects for Delayed Adverse Events."1 The LTFU study seeks to provide longitudinal information, and should adverse events occur, more timely discovery and treatment.
Zoladex 3.6 mg (goserelin acetate) will be injected once every 4 weeks (± 7 days). One oral tamoxifen 20 mg tablet will also be taken daily.
The PNE will follow the principles established by Explain Pain, addressing reconceptualization of pain, emphasizing modern neuroscience concepts. The PNE workshop will last 40 minutes (2 sessions). The movement control exercises will consist of active exercises that address posture and control of movements which are impaired and trigger pain. The session will last approximately 30 minutes, starting with the execution of the coordination exercises in the control of movement with an intensity of 10 to 30 repetitions and then performing exercises for stretching in 3 series of 30 seconds. Finally, strengthening exercises in 3 sets of 15 repetitions will be implemented. The exercises will be administered 1 session/week (volunteers will be oriented to execute the same exercises at home twice a week). The volunteers will receive 8 sessions at the clinic.
Patients will receive neoadjuvant chemotherapy alone with carboplatin AUC 5 D1 and paclitaxel 80mg/m² D1 D8 D15 and cemiplimab 350 mg D1-D21 (3 cycles of 4 weeks). Patients will subsequently receive curative hypofractionated radiotherapy (55 Gy/20fr). After radiotherapy, patients will receive maintenance immunotherapy with Cemiplimab 350 mg every 3 weeks for a period of 12 months.
Patients allocated to the standard care arm will receive routine intensive care for hypoxic respiratory failure, including mechanical ventilation as per local practices, weaning of sedation and assessment for extubation. Patients who continue to deteriorate will be eligible for initiation of V-V ECMO if they meet the ECMO to rescue lung injury in severe ARDS (EOLIA) criteria: Partial pressures of arterial oxygen (PaO2):Fraction of inspired oxygen (FiO2)\<50 for 3 hours, PaO2:FiO2\<80 for 6 hours, pH\<7.25 with PaCO2 \>60 for \>6 hours.
A novel cellular product composed of chemically-treated macrophages for treating fibrosis diseases. The cellular product has the beneficial effect of protecting organs against fibrosis-induced lesions and dysfunction by reducing collagen content. The macrophages are treated with mitochondrial respiratory chain inhibitors and cultured under hypoxia conditions. They express a higher level of anti-fibrosis bio-markers and a reduced level of pro-fibrosis bio-markers. The macrophages can be administered to animals with pulmonary fibrosis via tail vein or intratracheal injection. The invention can also be used to treat patients with Idiopathic Pulmonary Fibrosis, liver fibrosis, myocardial fibrosis, and renal fibrosis. A novel technique produces and manufactures cellular products for therapeutic purposes by using tissue culture vehicles coated with temperature-responsive polymer material. This novel technique has a clear advantage in growing more cells and preserving cell integrity compared to conventional methods.
Cetuximab + mFOLFOX6: Cetuximab (500mg/m2 IV ) will be given. Oxaliplatin (85 mg/m2 IV over 2 h on day 1), Leucovorin calcium (350 mg/m2 IV over 2 h on day 1) plus a bolus of 5FU (400 mg/m2) followed by a 46h-48h IV infusion of 5FU 2400 mg/m2 will be repeated for every 2 weeks. The regimens repeat every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
OBJECTIVE: This study aimed to evaluate the efficacy and safety of neuroendoscopy for treating hypertensive putamen hemorrhage (HPH), compared with traditional craniotomy.
METHODS: We retrospectively analyzed 81 consecutive patients with HPH treated with neuroendoscopy (n=36) or craniotomy (n=45) in the Department of Neurosurgery at the Anhui Provincial Hospital Affiliated to Anhui Medical University between January 2015 and December 2017. We compared the clinical and radiographic outcomes, excluded 14 patients who did not meet the inclusion criteria. Patient characteristics in emergency room were recorded. In addition, hospitalization days, total cost during hospitalization, operative time, blood loss, evacuation rate, rebreeding, intracranial infection, pulmonary infection, epilepsy, hemorrhage of digestive tract, venous thrombus, hypoproteinemia, aphasia, oculomotor paralysis, mortality, Modified Rankin Scale score 6 months after surgery, and Glasgow Outcome Scale score 6 months after surgery were compared between the 2 groups.
RESULTS: Comparative analysis of preoperative patient data revealed no notable disparities. Neuroendoscopic surgery afford distinct benefits including reduced operative time, minimal patient blood loss, and enhanced efficacy in hematoma evacuation. However, the incidence of postoperative complications such as rebleeding, intracranial infections, pulmonary infections, postoperative epilepsy, hemorrhage of digestive tract, venous thrombus, hypoproteinemia, aphasia, and oculomotor paralysis did not significantly differ. In contrast, endoscopic techniques, relative to conventional craniotomy for hematoma evacuation, are characterized by less invasive incisions, a marked decrease in the duration of hospitalization, and a substantial reduction in associated healthcare costs. Furthermore, endoscopic techniques contribute to superior long-term recuperative outcomes in patients, without altering mortality rates.
CONCLUSIONS: In comparison to the conventional method of craniotomy, the utilization of neuroendoscopy in the treatment of hypertensive putamen hemorrhage (HPH) may offer a more efficacious, minimally invasive, and cost-effective approach. This alternative approach has the potential to decrease the length of hospital stays and improve long-term neurologic outcomes, without altering mortality rates.
ETHNOPHARMACOLOGICAL RELEVANCE: In Traditional Chinese Medicine (TCM), cholestasis liver disease belongs to jaundice. Yinchenzhufu decoction (YCZFD) is a classic formula used for treating jaundice.
AIM OF THE STUDY: This study was aimed to investigate the potential mechanism and effective components of YCZFD in chronic cholestatic liver injury (CCLI).
MATERIALS AND METHODS: A chronic cholestatic mouse model induced by 3, 5-diethoxycarbonyl-1, 4-dihydroxychollidine was used to investigate the effect of YCZFD. Then, metabolomics was used to investigate the metabolites influenced by YCZFD. Serum and liver bile acid (BA) levels were measured using liquid chromatography coupled with triple quadruple mass spectrometry (LC-MS/MS), and the gene and protein expressions of BA transporters and metabolic enzymes were detected. Additionally, the pharmacokinetics of multiple components of YCZFD was explored to clarify the potential effective components. The effects of absorbed components of YCZFD on BA metabolism and transporter function, inflammation, and farnesoid X receptor (FXR) and pregnane X receptor (PXR) activation were analyzed using sandwich cultured rat hepatocytes, AML12 cells, and dual-luciferase receptor systems, respectively.
RESULTS: YCZFD decreased the liver damage in chronic cholestatic mice. Serum metabolomics results indicated that the main pathways influenced by YCZFD involved primary BA biosynthesis and arachidonic acid metabolism. YCZFD upregulated the expression of FXR, PXR, and BA efflux transporters and the metabolic enzymes of liver tissues, promoting BA excretion and metabolism in cholestatic mice. Additionally, YCZFD downregulated the expression of genes and proteins of the toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) pathway and decreased liver inflammation. The pharmacokinetic study indicated that multiple components showed different pharmacokinetic properties. Among the absorbed components of YCZFD, multiple components activated the transcription of FXR and PXR, regulated BA transporters and metabolic enzyme function, and reduced the gene expression of TLR4 and NF-κB1.
CONCLUSION: YCZFD can ameliorate CCLI by promoting the excretion and metabolism of BAs and inhibiting inflammation via the TLR4/NF-κB signaling pathway. The multiple components of YCZFD could act on BA homeostasis regulation and anti-inflammation, exhibiting a combined effect against CCLI.
PURPOSE: Cochlear implantation is a well-established option for early intervention. Children with hearing impairment and their parents are users of intervention services, with parents being more suited to provide insight into their experiences. The purpose of the current study was to describe the experiences of parents of children with cochlear implants (CIs) in the South African context.
METHODS: A qualitative research design was employed. Non-probability, purposive sampling was used. Seven, online semi-structured interviews were conducted with parents of children with CIs. Data were analysed using inductive thematic analysis.
RESULTS: Participants expressed feelings of certainty and assurance in the CI journey. Participants extended gratitude to the healthcare professionals involved in their children's CI journey. Feelings of doubt and stress were noted when coming to terms with the decision of cochlear implantation and financial stressors were noted as a challenge. Many participants found it challenging transitioning their children into school.
CONCLUSIONS: Parents conveyed having no regrets with their decision of cochlear implantation for their child and were grateful for the support provided by healthcare professionals. However, financial, and educational challenges remain. Findings suggest the need for more financial support for cochlear implantation in South Africa, and for adequate inclusive educational settings.
Both neuroinflammation and iron accumulation play roles in the pathogenesis of Parkinson's disease (PD). However, whether inflammation induces iron dyshomeostasis in dopaminergic neurons at an early stage of PD, at which no quantifiable dopaminergic neuron loss can be observed, is still unknown. As for the inflammation mediators, although several cytokines have been reported to increase in PD, the functions of these cytokines in the SN are double-edged and controversial. In this study, whether inflammation could induce iron dyshomeostasis in dopaminergic neurons through high mobility group protein B1 (HMGB1) in the early stage of PD is explored. Lipopolysaccharide (LPS), a toxin that primarily activates glia cells, and 6-hydroxydopamine (6-OHDA), the neurotoxin that firstly impacts dopaminergic neurons, were utilized to mimic PD in rats. We found a common and exceedingly early over-production of HMGB1, followed by an increase of divalent metal transporter 1 with iron responsive element (DMT1+) in the dopaminergic neurons before quantifiable neuronal loss. HMGB1 neutralizing antibody suppressed inflammation in the SN, DMT1+ elevation in dopaminergic neurons, and dopaminergic neuronal loss in both LPS and 6-OHDA administration- induced PD models. On the contrary, interleukin-1β inhibitor diacerein failed to suppress these outcomes induced by 6-OHDA. Our findings not only demonstrate that inflammation could be one of the causes of DMT1+ increase in dopaminergic neurons, but also highlight HMGB1 as a pivotal early mediator of inflammation-induced iron increase and subsequent neurodegeneration, thereby HMGB1 could serve as a potential target for early-stage PD treatment.
BACKGROUND: Molecular surveillance of infectious diseases allows the monitoring of pathogens beyond the granularity of traditional epidemiological approaches and is well-established for some of the most relevant infectious diseases such as malaria. The presence of genetically distinct pathogenic variants within an infection, referred to as multiplicity of infection (MOI) or complexity of infection (COI) is common in malaria and similar infectious diseases. It is an important metric that scales with transmission intensities, potentially affects the clinical pathogenesis, and a confounding factor when monitoring the frequency and prevalence of pathogenic variants. Several statistical methods exist to estimate MOI and the frequency distribution of pathogen variants. However, a common problem is the quality of the underlying molecular data. If molecular assays fail not randomly, it is likely to underestimate MOI and the prevalence of pathogen variants.
METHODS AND FINDINGS: A statistical model is introduced, which explicitly addresses data quality, by assuming a probability by which a pathogen variant remains undetected in a molecular assay. This is different from the assumption of missing at random, for which a molecular assay either performs perfectly or fails completely. The method is applicable to a single molecular marker and allows to estimate allele-frequency spectra, the distribution of MOI, and the probability of variants to remain undetected (incomplete information). Based on the statistical model, expressions for the prevalence of pathogen variants are derived and differences between frequency and prevalence are discussed. The usual desirable asymptotic properties of the maximum-likelihood estimator (MLE) are established by rewriting the model into an exponential family. The MLE has promising finite sample properties in terms of bias and variance. The covariance matrix of the estimator is close to the Cramér-Rao lower bound (inverse Fisher information). Importantly, the estimator's variance is larger than that of a similar method which disregards incomplete information, but its bias is smaller.
CONCLUSIONS: Although the model introduced here has convenient properties, in terms of the mean squared error it does not outperform a simple standard method that neglects missing information. Thus, the new method is recommendable only for data sets in which the molecular assays produced poor-quality results. This will be particularly true if the model is extended to accommodate information from multiple molecular markers at the same time, and incomplete information at one or more markers leads to a strong depletion of sample size.