anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
AIMS: Gene therapy with cardiac phosphodiesterases (PDEs), such as phosphodiesterase 4B (PDE4B), has recently been described to effectively prevent heart failure (HF) in mice. However, exact molecular mechanisms of its beneficial effects, apart from general lowering of cardiomyocyte cyclic adenosine monophosphate (cAMP) levels, have not been elucidated. Here, we studied whether gene therapy with two types of PDEs, namely PDE2A and PDE4B, can prevent pressure-overload-induced HF in mice by acting on and restoring altered cAMP compartmentation in distinct subcellular microdomains.
METHODS AND RESULTS: HF was induced by transverse aortic constriction followed by tail-vein injection of adeno-associated-virus type 9 vectors to overexpress PDE2A3, PDE4B3, or luciferase for 8 weeks. Heart morphology and function was assessed by echocardiography and histology which showed that PDE2A and especially PDE4B gene therapy could attenuate cardiac hypertrophy, fibrosis, and decline of contractile function. Live cell imaging using targeted cAMP biosensors showed that PDE overexpression restored altered cAMP compartmentation in microdomains associated with ryanodine receptor type 2 (RyR2) and caveolin-rich plasma membrane. This was accompanied by ameliorated caveolin-3 decline after PDE2A3 overexpression, reduced RyR2 phosphorylation in PDE4B3 overexpressing hearts, and antiarrhythmic effects of both PDEs measured under isoproterenol stimulation in single cells. Strong association of overexpressed PDE4B but not PDE2A with RyR2 microdomain could prevent calcium leak and arrhythmias in human-induced pluripotent stem-derived cardiomyocytes with the A2254V mutation in RyR2 causing catecholaminergic polymorphic ventricular tachycardia.
CONCLUSION: Our data indicate that gene therapy with phosphodiesterases can prevent HF including associated cardiac remodelling and arrhythmias by restoring altered cAMP compartmentation in functionally relevant subcellular microdomains.
It is unknown whether imaging technologies have broad applications in brain mapping due to limited knowledge of the value of the results. Accurate identification of areas of eloquent brain function is vital to surgical decision making and to preservation of independence as patients with brain tumors who are higher functioning have better survival outcomes. Imaging technology has evolved to provide multiple non-invasive modalities for pre-operative testing of eloquent brain function and include functional MRI (fMRI) and magnetoencephalography (MEG). Eloquent brain is defined as a region controlling language, motor, or sensory function such that without its proper input, a person would be left with significant neurologic deficits. Studies conducted have shown that these non-invasive mapping modalities provide useful information, however, the information provided inconsistently predicts distribution of eloquent function.

Direct electrical stimulation (DES) at the time of surgery allows assessment of eloquent function directly from the brain surface (invasive) and is considered the gold standard in brain mapping. Therefore, in order to determine the true clinical applicability of the non-invasive mapping technologies, this study proposes to: (1) assess the predictive value of fMRI and MEG for sensorimotor and language functions by comparing their results to DES and (2) determine whether fMRI or MEG provides the most consistent and accurate information. These aims will be accomplished by by co-registering all mapping data (invasive and non-invasive) in a modifiable 3D rendering. In this way, the DES to fMRI and MEG can be evaluated as well as fMRI to MEG compared. The rationale for the proposed research is that understanding the reliability of our current technology will allow for safer surgeries and preservation of neurologic function. The expected outcomes for the work proposed in Aims 1 and 2 are identification of a predictive value for fMRI and MEG and determination if one modality should be utilized over the other pre-operatively for the most accurate information. The results of this study are expected to have an important positive impact because identification of accurate pre-operative non-invasive mapping modalities will allow tailored testing and possibly lead to negation of the need for intra-operative mapping in certain cases. It will also enhance patient outcomes by improving patient safety. Furthermore, it will serve as the basis for a multi-institutional mapping data bank.
BACKGROUND: Vitiligo is an auto-immune progressive depigmentation disorder of the skin due to loss of melanocytes. Genetic risk is one of the important factors for development of vitiligo. Preponderance of vitiligo in certain ethnicities is known which can be analysed by understanding the distribution of allele frequencies across normal populations. Earlier GWAS identified 108 risk alleles for vitiligo in Europeans and East Asians. In this study, 64 of these risk alleles were used for analysing their enrichment and depletion across populations (1000 Genomes Project and IndiGen) with reference to 1000 Genomes dataset. Genetic risk scores were calculated and Fisher's exact test was performed to understand statistical significance of their variation in each population with respect to 1000 Genomes dataset as reference. In addition to SNPs reported in GWAS, significant variation in allele frequencies of 1079 vitiligo-related genes were also analysed. Two-tailed Chi-square test and Bonferroni's multiple adjustment values along with fixation index (≥ 0.5) and minimum allele frequency (≥ 0.05) were calculated and used to prioritise the variants based on pairwise comparison across populations.
RESULTS: Risk alleles rs1043101 and rs10768122 belong to 3 prime UTR of glutamate receptor gene SLC1A2 are found to be highly enriched in the South Asian population when compared with the 'global normal' population. Intron variant rs4766578 (ATXN2) was found to be deleted in SAS, EAS and AFR and enriched in EUR and AMR1. This risk allele is found to be under positive selection in SAS, AMR1 and EUR. From the ancillary vitiligo gene list, nonsynonymous variant rs16891982 was found to be enriched in the European and the Admixed American populations and depleted in all others. rs2279238 and rs11039155 belonging to the LXR-α gene involved in regulation of metalloproteinase 2 and 9 (melanocyte precursors) were found to be associated with vitiligo in the North Indian population (in earlier study).
CONCLUSION: The differential enrichment/depletion profile of the risk alleles provides insight into the underlying inter-population variations. This would provide clues towards prioritisation of SNPs associated with vitiligo thereby elucidating its preponderance in different ethnic groups.
The present invention relates to a weak alkaline carbazitaxel derivative and a formulation thereof, and specifically relates to the synthesis of the weak alkaline carbazitaxel derivative, a liposome formulation comprising the derivative, and use of the derivative in a drug delivery system, belonging to the technical field of medical technologies. The weak alkaline carbazitaxel derivative connects carbazitaxel to a weak alkaline intermediate by means of an ester bond, and the ester bond can be broken by means of the action of esterase in vivo, so as to release an active drug. The structural formula thereof is as follows: wherein a linker is a C<sub>1</sub>-C<sub>4</sub> alkyl, C<sub>3</sub>-C<sub>6</sub> cycloalkyl or phenyl; [N] is N-methylpiperazinyl, piperidinyl, 4-(1-piperidinyl)piperidinyl, morpholinyl, tetrahydropyrrolyl, or other tertiary amine structure. The weak alkaline cabazitaxel derivative can be used to prepare a liposome formulation. The liposome formulation has the characteristics of high drug loading, high encapsulation efficiency, and good stability. After the administration by injection, the liposome formulation can greatly improve the circulation time of the drug in vivo, increase the accumulation amount of the drug in the tumor site, and improve the anti-tumor effect and tolerance dosage.
OBJECTIVES: To observe the effect of electroacupuncture (EA) on the expression of synaptic function related proteins PSD95 and MeCP2 and synaptic ultrastructure in sleep deprived rats, so as to explore its mechanism underlying improvement of learning and memory ability caused by sleep deprivation.
METHODS: SD rats were randomly divided into normal, model, EA and sham EA groups (n=10). The sleep deprivation model was prepared by modified multi-platform water environment. Rats of the EA group received EA stimulation at "Baihui" (GV20) and "Dazhui" (GV14), while the sham EA group received shallow needling 4 mm away from the above acupoints without electrical stimulation. The learning and memory ability was evaluated with Morris water maze test. The density of dendritic spines in hippocampal CA1 region was detected by Golgi staining. The synaptic ultrastructure of hippocampus was observed by electron microscope. The protein expression levels of PSD95 and MeCP2 in hippocampus was detected by Western blot.
RESULTS: Compared with the normal group, the escaping latency of the positioning navigation experiment in the model group was prolonged (P<0.05), the number of crossing the platform and the residence time in the target quadrant were decreased(P<0.05), the density of dendritic spines in the hippocampal CA1 area was decreased (P<0.05), the number of synapses was reduced, with swollen synaptosomes, blurred synaptic structure, disappeared and narrowed synaptic clefts, the protein expression levels of PSD95 and MeCP2 were significantly decreased (P<0.05) in the model group. Compared with the model group, the escape latency of the positioning navigation experiment was shortened (P<0.05), the number of crossing platforms and the time spent in the target quadrant were increased (P<0.05), the density of dendritic spines in the hippocampal CA1 region was increased (P<0.05), the morphology of synaptic improved, the protein expression levels of PSD95 and MeCP2 were increased (P<0.01) in the EA and sham EA groups. The improvement of the above indexes in EA group was more obvious than those in sham EA group.
CONCLUSIONS: EA can improve the learning and memory of sleep deprivation rats, which may be related to its function in regulating the expressions of synaptic related proteins PSD95 and MeCP2, and improving the synaptic structure.
Severe combined immunodeficiency (SCID) is a genetically heterogeneous life-threatening disease characterized by severely impaired T cell development with or without impaired natural killer (NK) and B cell development or function depending on the genetic defect. Mutations in recombination activating genes 1 and 2 (RAG1 and RAG2) represent about 20% of all types of SCID. SCID is a paediatric emergency since it leads to severe and recurrent infections often in combination with protracted diarrhoea and failure to thrive. When left untreated, it is usually fatal within the first year of life. Currently, the only curative treatment option for RAG-deficient SCID is allogeneic hematopoietic stem cell transplantation (HSCT). Despite improvements in HSCT in recent years, this treatment is associated with serious potential complications like graft-versus-host disease which results in an unfavourable outcome, particularly in patients who lack a human leukocyte antigen (HLA)-matched donor. In recent years, gene therapy based on transplantation of autologous gene-corrected hematopoietic stem cells (HSC) has evolved as an effective and safe therapeutic option for X-linked and ADA-deficient forms of SCID. We have recently demonstrated that gene therapy using lentiviral (LV) self-inactivating (SIN) vectors expressing codon-optimized human RAG1 in a mouse model for RAG1-deficient SCID effectively restores T and B cell development and function. In this phase I/II explorative intervention study feasibility, safety and efficacy of gene therapy using gene-corrected autologous CD34+-selected mobilized peripheral blood or bone marrow cells will be investigated in patients with RAG1-deficient SCID with an indication for allogeneic HSCT but lacking an human leukocyte antigen (HLA)-matched donor.
In this single-arm study, patients will receive doses of \[161 Tb\]Tb PSMA I\&T on Day 1 of every 6 week Cycle. The dose of \[161 Tb\]Tb PSMA I\&T will vary in dose-escalation. Up to 6 Cycles will be given.
The invention relates to a method for producing a flowable, ready-to-be-compressed medical intermediate product. According to said method, dried plant drug material is wetted together with the desired additives, carrier and/or adjuvants in a vacuum drying apparatus. Said apparatus is provided with a multi-limb agitator with a drive of its own which agitator extends through a cylindrical mixer and drying chamber. The apparatus can be provided with a filter, a regeneration device, a solvent condenser with aftercooler and collecting container, a recondenser and/or a process, control and monitoring device. The wet mixture is dried at an outer temperature of the apparatus of 20 DEG C to 50 DEG C, a product temperature between 20 DEG C and 45 DEG C and a pressure of 20 to 500 mbar to obtain the intermediate product. The invention also relates to the intermediate products as such.
In short-term, controlled trials, in alcohol-dependent patients, the incidence of AST elevations associated with Naltrexone Injection treatment was similar to that observed with oral naltrexone treatment (1.5% each) and slightly higher than observed with placebo treatment (0.9%).

In the 6-month controlled trial conducted in opioid dependent subjects, 89% had a baseline diagnosis of hepatitis C infection, and 41% had a baseline diagnosis of HIV infection. There were frequently observed elevated liver enzyme levels (ALT, AST, and GGT); these were more commonly reported as adverse events in the naltrexone injection 380 mg group than in the placebo group. Patients could not enroll in this trial if they had a baseline ALT or AST value that was more than three times the upper limit of normal. More patients treated with naltrexone injection in this study experienced treatment-emergent elevations in transaminases to more than three times the upper limit of normal than patients treated with placebo. Shifts to more than three times the upper limit of normal occurred in 20% of patients treated with naltrexone injection as compared with 13% of placebo patients. Shifts in values of AST to more than three times the upper limit were also more common in the naltrexone injection (14%) arm compared with the placebo (11%) arm.

Opioid-dependent patients treated with naltrexone injection experienced a mean maximal increase from baseline ALT levels of 61 IU/L compared with 48 IU/L in placebo patients. Similarly for AST, opioid-dependent patients treated with naltrexone injection experienced a mean maximal increase from baseline AST levels of 40 IU/L compared with 31 IU/L in placebo patients.
A considerable fraction of population in the world suffers from rare diseases. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and its related Cas proteins offer a modern form of curative gene therapy for treating the rare diseases. Hereditary transthyretin amyloidosis, hereditary angioedema, duchenne muscular dystrophy and Rett syndrome are a few examples of such rare diseases. CRISPR/Cas9, for example, has been used in the treatment of β-thalassemia and sickle cell disease (Frangoul et al., 2021; Pavani et al., 2021) [1,2]. Neurological diseases such as Huntington's have also been focused in some studies involving CRISPR/Cas (Yang et al., 2017; Yan et al., 2023) [3,4]. Delivery of these biologicals via vector and non vector mediated methods depends on the type of target cells, characteristics of expression, time duration of expression, size of foreign genetic material etc. For instance, retroviruses find their applicability in case of ex vivo delivery in somatic cells due to their ability to integrate in the host genome. These have been successfully used in gene therapy involving X-SCID patients although, incidence of inappropriate activation has been reported. On the other hand, ex vivo gene therapy for β-thalassemia involved use of BB305 lentiviral vector for high level expression of CRISPR biological in HSCs. The efficacy and safety of these biologicals will decide their future application as efficient genome editing tools as they go forward in further stages of human clinical trials. This review focuses on CRISPR/Cas based therapies which are at various stages of clinical trials for treatment of rare diseases and the constraints and ethical issues associated with them.
The present application relates to an apparatus treating inflammation and/or infection within a synovial joint. The application is comprised of a depot (55), tether (60) and cap (70). The depot is comprised of a biodegradable polymer which is impregnated with a biological agent targeted to treat the inflammation and/or infection. The depot is inserted into the synovial joint through an incision or hole in the synovial membrane. A tether that extends from the depot is then thread back through the incision or hole and coupled to a cap such that the depot is coupled to the synovial membrane on an interior side of the synovial joint capsule and the cap is secured to the membrane on an exterior side of the synovial joint capsule. Once secured, the depot degrades and gradually releases the biological agent over a sustained time period.
The subject will take an oral pill called Lapatinib. Each tablet is 250 mg. Subjects will take 1500mg (six 250mg tablets) of lapatinib once daily. Subjects must fast 1 hour prior to and 1 hour following dosing. If a subject is unable to swallow lapatinib tablets whole, the lapatinib may be crushed with a mortar and pestle to form a powder, and mix it in 4 oz (120 ml) of water to take by mouth or through a feeding tube. Then the subject will then rinse the mortar with 2 oz (60ml) of water to suspend the left-over powder, and then swallow the rinse or flush it down the feeding tube. You will have to repeat this rinse one more time.

Subjects will have a "MUGA" scan done at the very beginning to make sure that heart function is good. It will then be repeated every other month while on treatment. When the subjects have a MUGA scan, 3 cc's (less than one teaspoon) of blood will be drawn from your vein, and labeled with a radioactive substance. Then, subjects blood will be injected back into his/her arm through a catheter in your vein. The level of radiation you will be exposed to is very minimal. Then, a camera will take a "movie" of your heart. The entire procedure lasts about 90 minutes.
Inertial measurement units (IMUs) offer a portable and quantitative solution for clinical movement analysis. However, their application in non-specific low back pain (NSLBP) remains underexplored. This study compared the spine and pelvis kinematics obtained from IMUs between individuals with and without NSLBP and across clinical subgroups of NSLBP. A total of 81 participants with NSLBP with flexion (FP; n = 38) and extension (EP; n = 43) motor control impairment and 26 controls (No-NSLBP) completed 10 repetitions of spine movements (flexion, extension, lateral flexion). IMUs were placed on the sacrum, fourth and second lumbar vertebrae, and seventh cervical vertebra to measure inclination at the pelvis, lower (LLx) and upper (ULx) lumbar spine, and lower cervical spine (LCx), respectively. At each location, the range of movement (ROM) was quantified as the range of IMU orientation in the primary plane of movement. The ROM was compared between NSLBP and No-NSLBP using unpaired t-tests and across FP-NSLBP, EP-NSLBP, and No-NSLBP subgroups using one-way ANOVA. Individuals with NSLBP exhibited a smaller ROM at the ULx (p = 0.005), LLx (p = 0.003) and LCx (p = 0.01) during forward flexion, smaller ROM at the LLx during extension (p = 0.03), and a smaller ROM at the pelvis during lateral flexion (p = 0.003). Those in the EP-NSLBP group had smaller ROM than those in the No-NSLBP group at LLx during forward flexion (Bonferroni-corrected p = 0.005), extension (p = 0.013), and lateral flexion (p = 0.038), and a smaller ROM at the pelvis during lateral flexion (p = 0.005). Those in the FP-NSLBP subgroup had smaller ROM than those in the No-NSLBP group at the ULx during forward flexion (p = 0.024). IMUs detected variations in kinematics at the trunk, lumbar spine, and pelvis among individuals with and without NSLBP and across clinical NSLBP subgroups during flexion, extension, and lateral flexion. These findings consistently point to reduced ROM in NSLBP. The identified subgroup differences highlight the potential of IMU for assessing spinal and pelvic kinematics in these clinically verified subgroups of NSLBP.
African American (AA) kidney recipients have a higher risk of allograft rejection and failure compared to non-AAs, but to what extent these outcomes are due to genetic versus environmental effects is currently unknown. Herein, we tested the effects of recipient self-reported race versus genetic proportion of African ancestry (pAFR), and neighborhood socioeconomic status (SES) on kidney allograft outcomes in multiethnic kidney transplant recipients from Columbia University (N = 1083) and the University of Pennsylvania (N = 738). All participants were genotyped with SNP arrays to estimate genetic admixture proportions. US census tract variables were used to analyze the effect of neighborhood factors. In both cohorts, self-reported recipient AA race and pAFR were individually associated with increased risk of rejection and failure after adjustment for known clinical risk factors and neighborhood SES factors. Joint analysis confirmed that self-reported recipient AA race and pAFR were both associated with a higher risk of allograft rejection (AA: HR 1.61 (1.31-1.96), P = 4.05E-06; pAFR: HR 1.90 (1.46-2.48), P = 2.40E-06) and allograft failure (AA: HR 1.52 (1.18-1.97), P = .001; pAFR: HR 1.70 (1.22-2.35), P = .002). Further research is needed to disentangle the role of genetics versus environmental, social, and structural factors contributing to poor transplantation outcomes in kidney recipients of African ancestry.
In the experimental group, 51 patients underwent endoscopic stricturoplasty. A transparent cap was mounted on the front end of the endoscope, and a needle knife was inserted through the working channel of the endoscope. Under direct visualization, a radial incision was made at the site of the stricture, with an effort to preserve normal mucosal tissue as much as possible. The stricture was gradually incised until the endoscope could smoothly pass through.
Participants with drug-sensitive tuberculous randomized to the NTZ arm will receive nitazoxanide 1000 mg po twice daily for 14 days. After this time point, participants will be switched to WHO standard tuberculosis therapy with isoniazid, rifampin, pyrazinamide and ethambutol.
FIELD: cosmetology, dermatology. SUBSTANCE: the present innovation deals with either cosmetic or dermatological compositions to protect skin and/or hair against ultraviolet radiation containing light-protective system in cosmetically and/or dermatologically acceptable carrier to be able to filter UV-radiation, and mixture of polyethylenes consisting of one polyethylene with terminal acid carboxylic function and one polyethylene. The present innovation refers, also, to the product for increasing protection factor against UV-radiation consisting of polyethylene with terminal acid carboxylic function in either free or partially or completely neutralized form and one polyethylene. The present innovation enables to obtain compositions with protection indices being higher against compositions with only one light-protective system. EFFECT: higher efficiency of protection. 17 cl, 9 tbl