anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Recently, mRNA-based therapeutics, including vaccines, have gained significant attention in the field of gene therapy for treating various diseases. Among the various mRNA delivery vehicles, lipid nanoparticles (LNPs) have emerged as promising vehicles for packaging and delivering mRNA with low immunogenicity. However, while mRNA delivery has several advantages, the delivery efficiency and stability of LNPs remain challenging for mRNA therapy. In this study, an ionizable helper cholesterol analog, 3β[L-histidinamide-carbamoyl] cholesterol (Hchol) lipid is developed and incorporated into LNPs instead of cholesterol to enhance the LNP potency. The pKa values of the Hchol-LNPs are ≈6.03 and 6.61 in MC3- and SM102-based lipid formulations. Notably, the Hchol-LNPs significantly improve the delivery efficiency by enhancing the endosomal escape of mRNA. Additionally, the Hchol-LNPs are more effective in a red blood cell hemolysis at pH 5.5, indicating a synergistic effect of the protonated imidazole groups of Hchol and cholesterol on endosomal membrane destabilization. Furthermore, mRNA delivery is substantially enhanced in mice treated with Hchol-LNPs. Importantly, LNP-encapsulated SARS-CoV-2 spike mRNA vaccinations induce potent antigen-specific antibodies against SARS-CoV-2. Overall, incorporating Hchol into LNP formulations enables efficient endosomal escape and stability, leading to an mRNA delivery vehicle with a higher delivery efficiency.
Ocular inflammatory diseases can lead to visual loss in adults as well as in children. These conditions are usually characterized by repeated exacerbations and remissions. The underlying cause of majority of these conditions is not clear even though an autoimmune mechanism has been implicated. Various studies have reported an altered immunological profile in these patients. An underlying immune mechanism has been thought to be playing a role in at least some of the ocular inflammatory diseases. In addition, evidence from literature also suggests inflammatory disease may be an important mechanism leading to Age related macular degeneration and Diabetic retinopathy, two leading causes for vision loss. However, very little is known about the involvement of immune components in these patients.

This protocol proposes to test for proliferative cell mediated and humoral responses against self-antigens from patients with ocular inflammatory diseases, AMD and diabetic retinopathy. Patients will be recruited from other ongoing protocols. An attempt would be made to find any correlation between the clinical disease and the immunological findings. These findings will not be used for diagnostic nor therapeutic purposes.
The present invention provides methods and compositions for preventing platelet aggregation and for treating individuals suffering from conditions or undergoing procedures that may result in unwanted platelet aggregation, e.g. heparin-induced thrombotic thrombocytopenia. In particular the invention provides to methods and compositions for arterial vessel pacification. The methods are based on the administration of a therapeutically effective amount of a glycoprotein IIb/IIIa receptor antagonist, e.g. xemilofiban. The treatment may commence prior to a medical or surgical procedure or an outbreak of a condition, either of which results in the activation of platelets that may lead to thrombus formation, and may continue thereafter.
Electroencephalogram (EEG) provides noninvasive measures of brain activity and is found to be valuable for the diagnosis of some chronic disorders. Specifically, pre-treatment EEG signals in the alpha and theta frequency bands have demonstrated some association with antidepressant response, which is well-known to have a low response rate. We aim to design an integrated pipeline that improves the response rate of patients with major depressive disorder by developing a treatment policy guided by the resting state pre-treatment EEG recordings and other treatment effects modifiers. First, we design an innovative automatic site-specific EEG preprocessing pipeline to extract features with stronger signals than raw data. We then estimate the conditional average treatment effect (CATE) using causal forests and use a doubly robust technique to improve efficiency in the estimation of the average treatment effect. We present evidence of heterogeneity in the treatment effect and the modifying power of the EEG features, as well as a significant average treatment effect, a result that cannot be obtained with conventional methods. Finally, we employ an efficient policy learning algorithm to learn an optimal depth-2 treatment assignment decision tree and compare its performance with Q-Learning and outcome-weighted learning via simulation studies and an application to a large multi-site, double-blind, randomized controlled clinical trial, EMBARC.
OBJECTIVES: The 2018 American Gastroenterological Association (AGA) guidelines strongly recommended early oral feeding as tolerated in patients with acute pancreatitis (AP). We compare early oral feeding rates in AP patients hospitalized in the periods before (2013-2016, Period A) and after (2019-2020, Period B) publication of the AGA guidelines, hypothesizing increased adherence in Period B.
METHODS: We performed a retrospective cohort study of AP patients presenting to the emergency department during each period. Early oral feeding was defined as diet initiation within the first 48 hours of presentation.
RESULTS: The cohort included 276 AP cases in period A and 104 in period B. A higher percentage of patients were offered early oral feeding during period B as compared to period A (70.2% vs. 43.5%). Similarly, more patients in period B were started on solid diet as compared to period A (34.6% vs. 20.3%). On multivariable regression analysis, the independent predictors of delayed oral feeding included early opioid analgesics use (OR 0.37), presence of pancreatic necrosis (OR 0.14), and organ failure (OR 0.33).
CONCLUSIONS: More AP patients were initiated on early oral feeding in the period following the publication of the AGA guidelines. Opioid analgesics use, pancreatic necrosis, and organ failure were associated with delayed oral feeding.
PCT No. PCT/SE92/00243 Sec. 371 Date Nov. 19, 1992 Sec. 102(e) Date Nov. 19, 1992 PCT Filed Apr. 14, 1992 PCT Pub. No. WO92/18545 PCT Pub. Date Oct. 29, 1992The invention relates to new heparin derivatives from bovine or porcine heparin which have a molecular weight equal to or larger than the standard heparin, show a sulfur content which is equal to or higher than that of the starting heparin or at least 13% w/w, have an anticoagulant activity in the anti-FXa assay of less than 10% of the standard heparin it was made from , show a ratio of APTT activity over anti-FXa activity of 3-35, show a reduced prolongation of bleeding time compared to the standard heparin it was made from as measured in the rat tail after i.v. administration and show enhancement of the rate of development of coronary collaterals in dogs equal to or better than clinically used heparin. The invention also relates to processes for preparation of the new bovine and porcine heparin derivatives. The use of this product for the manufacturing of a medicament for treatment of ischemic heart disease and related vascular disorders and for the enhancement of the rate of development of coronary collateral perfusion is disclosed.
Emerging evidence showed that chronic inflammation and neuro-progression underlie bipolar disorder (BP). There were several neurobiological similarities between neuro-progression in BP and aging. Patients of BP also had many changes that were associated with early senescence. Meta-analysis showed that the association between dementia and BP were stronger than those with major depressive disorder, too. Therefore, some researchers proposed the theory of bipolar disorder as an illness of accelerated aging. However, BP is frequently under-recognized and misdiagnosed, especially bipolar II disorder (BP-II). Although the lifetime prevalence rate of BP-II ranges around 3-11%, many with BP-II were misdiagnosed as major depressive disorder and did not receive appropriate treatment. Therefore, neuro-progression may be found after decades of disease onset. The neuro-progression process, as accelerated aging process, may occur in the middle age period in BP-II patients, and contribute to the cognitive deficits, which were typically shown in old aged subjects with neurocognitive disorder. However, most of the past studies focused on bipolar I disorder (BP-I), there were few studies to investigate the early neuro-progression process in BP-II. Treatments for the cognitive deficits in middle-to-old aged BP-II patients were also lacked in literature.

Memantine (MM) has neuroprotective effects through the mechanisms of reducing neuroinflammation and increasing neurotrophic factors. The previous study showed that add-on low dose MM with mood stabilizers may attenuate inflammatory status and improve metabolic dysregulation in BP patients. Therefore, the investigators hypothesized that add-on MM 5 mg/day may reduce chronic inflammation, and subsequently improve neuro-progression process and cognitive function in middle-to-old aged BP-II patients. In current proposal, the investigators will conduct a randomized double-blind placebo-controlled study. The investigators will recruit 100-120 patients with BP-II who are older than 40 years old in three years, and allocate them to add-on MM or placebo plus standard valproic acid treatment in a 1: 1 ratio. The investigators will follow up the participants for 12 weeks and measure the severity of mood symptoms, neuropsychological tests and inflammatory markers to evaluate the therapeutic effects of add-on MM. The current proposal will provide the important data in whether add-on MM is able to improve the cognitive deficits due to neuro-progression in BP-II, and to prevent disease progression to a more severe form of neurocognitive disorder.
This study aimed to evaluate the safety and efficacy of delayed reconstruction of the perforator pedicle propeller flap after the induced membrane technique in the treatment of Gustilo IIIB open distal tibial fracture, and to evaluate the clinical outcome and complications of two different perforator pedicle propeller flaps.Thirty-four patients with Gustilo IIIB open distal tibial fractures treated by the induced membrane technique and delayed reconstruction of two different perforator pedicle propeller flaps from May 2017 to March 2022 were retrospectively analyzed. Patients were divided into two groups according to the different kinds of perforator pedicle propeller flaps covered. The operation required two stages. The Radiographic Union Score for Tibial fractures (RUST) was used to evaluate the healing of the tibial bone defect. The American Orthopaedic Foot and Ankle Society (AOFAS) score was used to evaluate ankle function. The complications associated with the technique were recorded.The number of serial debridements, excluding those performed during emergency and final operations, was a mean of 2.28 ± 0.83 in the PAPF group. The PAPF group had a mean bone defect length of 6.76 ± 0.69 cm, the median healing time of 13.11 ± 0.96 months, RUST score 12.68 ± 1.63, and AOFAS score of 84.12 ± 6.38. On the other hand the PTAPF group's mean bone defect length was 6.73 ± 0.95 cm, the median healing time 12.63 ± 1.46 months, RUST score 13.73 ± 1.53 and AOFAS score 82.79 ± 5.49. There were no observed significant differences the two groups in the number of serial debridements, bone defect length, bone union time, RUST score, or AOFAS score (p > 0.05). Flap size ranged from 9 × 6 cm2 to 14 × 7 cm2 in the PAPF group and from 9 × 6 cm2 to 13 × 7 cm2 in the PTAPF group. There were no severe complications such as flap-related complications or amputation. The differences in complications in the two groups were not statistically significant.In cases of severe open tibial fracture, the reconstructive method is important. When delayed reconstruction is inevitable, surgeons should first perform radical debridement, followed by vacuum sealing drainage as a bridging therapy; both PAPF and PTAPF can be considered for definitive soft tissue coverage.
<P>PROBLEM TO BE SOLVED: To provide a mesenchymal cell for formation of tooth capable of efficiently obtaining tooth retaining characteristic cell configuration and efficiently obtain the tooth in which characteristic cell configuration is retained.  <P>SOLUTION: A totipotent stem cell, e.g. embryonic carcinoma cell is cultured in the presence of a differentiation-inducing agent such as dimethyl sulfoxide, and the CD44-positive and CD29-positive cell or the CD44-positive and CD106-positive cell is selected from the differentiation-induced cell population as a tooth-forming mesenchymal cell. A first cell population comprising substantially only either one of a mesenchymal cell and an epithelial cell and a second cell population comprising substantially only the other are placed in the inside of a carrier which can allow the cells to be in contact with each other in a closely adhered state without mixing them and the cell populations are cultured, wherein the mesenchymal cell comprises the tooth-forming mesenchymal cell. As a result, the tooth having characteristic cell configuration is obtained.  <P>COPYRIGHT: (C)2008,JPO&INPIT
Silencing of Influenza virus RNA can be achieved by siDNA. These are oligodeoxynucleotides consisting of an antisense-strand homologous to the viral RNA and a second strand, partially complementary to the antisense-strand. The two strands are preferentially linked by a linker (eg 4 thymidines). Triple-helix formation with the target RNA is a preferred effect. The siDNA is superior to siRNA because it acts earlier, is easier taken up by the cell, the formation of RNA-DNA hybrids is preferred over double-stranded DNA or double-stranded RNA, which forms as tertiary structures in RNA genomes. Also the induction of interferon is less likely. siDNA is easier to synthesize and it is more stable. It can be combined with siRNA.
Varicella-zoster virus belongs to the herpesvirus family and its main host are humans, producing 2 different diseases: varicella in children and young adults and zoster in elder or immunodepressed subjects. We reported in the scientific medical literature the unexpected finding that the role of varicella-zoster virus in the pathogeny of Multiple Sclerosis (Archives of Neurology 61: 529-532, 2004). This finding allows us to foresee the use of a vaccine against this virus with preventive and therapeutic ends for multiple sclerosis which eventually could also be applicable in the prevention of varicella and zoster. Currently the only vaccine used in humans is that produced by attenuated live varicella-zoster viruses, this latter feature thus avoiding its therapeutic use in multiple sclerosis, wherein the chronic disease is caused by periodic exacerbations of the virus which remains latent in the host, therefore by injecting an attenuated and viable virus the infection may be exacerbated and promote the very latency of the vaccine virus. Our researches show that the most predominant genes of the varicella-zoster virus found in patients suffering multiple sclerosis were those corresponding to the ORF31 (gB), ORF67 (gI) and ORF68 (gE) genes. The recombinant vaccine of the present invention is constituted by proteins resulting from the aforementioned genes, said genes being inserted into a pNMT1-TOPO vector plasmid so as to transform Schizosaccharomyces pombe and obtain the recombinant viral proteins forming the vaccine. Said vaccine previously obtained from recombinant viral proteins avoids the risks associated with the use of vaccines from attenuated viable viruses. Moreover the use of the recombinant viral proteins is specific and sensitive to serological tests for the diagnostic of infections caused by varicella-zoster virus.
A total of 29 medically healthy patients (12 females and 17 males; age range 28-49 years, mean±SD: 38.22±8.21) with chronic periodontitis at the outpatient Ataturk University, Department of Periodontology, Faculty of Dentistry, Erzurum, Turkey, were selected for the study. The study, conducted from November 2015 to June 2016, was planned as a randomized, double-blinded, controlled clinical trial that used a split-mouth design. This study was proved by the ethics committee of Ataturk University Faculty of Dentistry, and all patients received verbal information regarding participation and provided written informed consent for including to the study.

Bone loss characteristics of the patients were diagnosed with full-mouth radiographs and cone-beam computed tomography. This study included the patients with moderate-to-severe chronic periodontitis with a probing depth of 5 mm or deeper and horizontal bone loss (one- or two-wall shallow interproximal defects) of at least two quadrants of the jaws after Phase-I periodontal therapy. After re-evaluating the results of Phase-I therapy, patients with any of the following were excluded from the study: 1) smoking or tobacco use in any form; 2) medications known to affect periodontal treatment and blood coagulation; 3) systemic conditions known to affect periodontal status; 4) pregnancy/lactation; and 5) poor oral hygiene (plaque index \[PI\] \>1.5) (Sillness and Loe; 1964). Patients with teeth with 3-wall intrabony defects, gingival recession, endodontic lesion, or furcation involvement were also excluded.
Medication non-adherence is a problem that affects up to 50% of patients with chronic diseases. The result is a failure to achieve therapeutic goals and an increased burden on the healthcare system. It is, therefore, highly appropriate to develop models to assess patient adherence to prescribed therapy. To date, there are many methods for doing this. However, several tools have been developed that subjectively or objectively, directly or indirectly, assess the level of patient adherence. Electronic medication packaging devices are among the most rapidly evolving methods of measuring adherence. Other emerging technologies include the use of artificial intelligence algorithms and ingestible biosensors. The former is being used to create applications for mobile phones and laptops. The latter appears to be the least susceptible to the risk of overestimating adherence but remains very expensive. Here, we present recent developments in measuring patient adherence, and provide details of achievements in objective methods for assessing adherence, such as electronic monitoring devices, video-observed therapy, and ingestible biosensors. A dedicated section on using artificial intelligence and machine learning in adherence measurement and reviewing questionnaires and scales used in specific diseases is also included. Methods are discussed along with their advantages and potential limitations. This article aimed to review current measures and future initiatives to improve patient medication adherence.
Human schistosomiasis is a parasitic disease caused by an infection with trematodes of the genus Schistosoma. The disease mainly affects impoverished populations. Around 800 million people are exposed to the infection, which is a public health problem in the tropical and subtropical regions of Africa, Asia, the Caribbean and South America. In Brazil, Schistosoma mansoni is the only species that causes schistosomiasis and the disease is widely distributed. Conventional diagnosis of the disease is carried out by detecting eggs using parasitological methods, such as the Kato-Katz test. Schistosomiasis has been reported in all regions of Brazil and is characterized as endemic in seven states in the Northeast Region and two states in the Southeast Region. In 2015, 78,7% of all cases reported in Brazil occurred in the Northeast Region. It is estimated that 1,5 million people is infected with this disease in Brazil and more than 25 millions live in areas with a high risk of transmission. Despite the reduction in mortality and morbidity, schistosomiasis was responsible for 8,756 deaths between 2000 and 2011 and 2,517 deaths between 2015 and 2019 in Brazil and it remains an important public health problem. In the state of Rio de Janeiro, some areas have low endemicity or isolated foci of Schistosoma mansoni and the majority of infected individuals have mild infections. The last survey of the disease in the state of Rio de Janeiro was carried out between 2010 and 2015 in students aged 7 to 17.Schistosomiasis was reported in 10 of the 21 municipalities studied. Of the 5,111 school children screened for S. mansoni infection, 46 (1,65%) were tested positive. Studies carried out in areas of low endemicity in Rio de Janeiro showed that among the 205 patients infected by S. mansoni in Sumidouro, around 84% were aged 14 or over and all, except one individual, had the intestinal form (91,2%) or hepato-intestinal (8,3%) of schistosomiasis. Another study carried out in Sumidouro showed that with tests based on patent Schistosoma egg infection determined by the Kato-Katz test, active infections were diagnosed in eight (8/108) individuals. The intensity of infection expressed by parasite loads ranged from 6 to 72 eggs per gram of feces/individual. The results showed DNA amplification in 32 of the 100 individuals tested by real-time PCR. All individuals with patent ovo infection showed positive DNA amplification. These studies showed that if we only analyzed school-age children using the Kato-Katz test, the majority of the infected population would never be diagnosed with S. mansoni infection. In situations of low endemicity, with low intensities of infection, with low severity in the population and in the most affected age groups, schistosomiasis requires a more sensitive diagnostic approach (e.g. screening by PCR rather than Kato test), otherwise many infected individuals will remain invisible to the healthcare system.
Risk Summary

Nirmatrelvir and ritonavir are present in human breast milk in small amounts (less than 2%). In a clinical lactation study in 8 lactating women, nirmatrelvir and ritonavir were estimated to be present in human milk at a mean weight-normalized infant daily dose of 0.16 mg/kg/day (1.8% of maternal weight-adjusted daily dose) and 0.006 mg/kg/day (0.2% of maternal weight-adjusted daily dose), respectively (see Data). 

There are no available data on the effects of nirmatrelvir or ritonavir on the breastfed infant or on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for PAXLOVID and any potential adverse effects on the breastfed infant from PAXLOVID or from the underlying maternal condition. Breastfeeding individuals with COVID-19 should follow practices according to clinical guidelines to avoid exposing the infant to COVID-19.

Data

In a clinical pharmacokinetics study, 8 healthy lactating women who were at least 12 weeks postpartum were administered 3 oral doses every 12 hours (steady state dosing) of 300 mg/100 mg nirmatrelvir/ritonavir. The mean daily amount of nirmatrelvir and ritonavir recovered in breast milk was 0.752 mg and 0.027 mg, respectively, representing 0.13% and 0.014% of the corresponding administered daily maternal doses (unadjusted for weight). The estimated daily infant dose (assuming average milk consumption of 150 mL/kg/day), was 0.16 mg/kg/day and 0.006 mg/kg/day, 1.8% and 0.2% of the maternal dose, respectively, for nirmatrelvir and ritonavir.