anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
The present disclosure provides Adenine Base Editors (ABEs) with background specificity, i.e., preference for pyrimidine located 5 'of the target adenosine, or preference for purine located 5' of the target adenosine. In addition, methods of targeted nucleic acid editing are provided. Further provided are pharmaceutical compositions comprising ABE. Vectors useful for generating and delivering ABE are also provided, including vector systems for engineering ABE by directed evolution. Cells containing such vectors and ABE are also provided. Further provided are therapeutic methods and uses comprising administration of ABE.
BACKGROUND: Biallelic pathogenic variants in USH2A lead to Usher syndrome or non-syndromic retinitis pigmentosa, and shown to have geographical and ethnical distribution in previous studies. This study provided a deeper understanding of the detailed clinical features using multimodal imaging, genetic spectrum, and genotype-phenotype correlations of USH2A-related retinal dystrophies in Taiwan.
RESULTS: In our cohort, the mean age at first visit was 47.66 ± 13.54 years, and the mean age at symptom onset, which was referred to the onset of nyctalopia and/or visual field constriction, was 31.21 ± 15.24 years. Among the variants identified, 23 (50%) were missense, 10 (22%) were splicing variants, 8 (17%) were nonsense, and 5 (11%) were frameshift mutations. The most predominant variant was c.2802T>G, which accounted for 21% of patients, and was located in exon 13. Patients with truncated alleles had significantly earlier symptom onset and seemly poorer disease progression regarding visual acuity, ellipsoid zone line length, and hypofluorescent lesions in the macula than those who had the complete gene. However, the clinical presentation revealed similar progression between patients with and without the c.2802T>G variant. During long-term follow-up, the patients had different ellipsoid zone line progression rates and were almost evenly distributed in the fast, moderate, and slow progression subgroups. Although a younger onset age and a smaller baseline intact macular area was observed in the fast progression subgroup, the results showed no significant difference.
CONCLUSIONS: This is the first cohort study to provide detailed genetic and longitudinal clinical analyses of patients with USH2A-related retinal dystrophies in Taiwan. The mutated allele frequency in exon 13 was high in Taiwan due to the predominant c.2802T>G variant. Moreover, truncated variants greatly impacted disease progression and determined the length of therapeutic windows. These findings provide insight into the characteristics of candidates for future gene therapies.
The invention discloses a carrier composition for nucleic acid transfer and application thereof in preparation of small interfering RNA drugs. The composition is obtained by uniformly mixing polyethylene glycol-polylactic acid and (polyamide-amine) -2-propionic acid-3-methyl maleic anhydride-polycaprolactone. The siRNA is added into the carrier composition solution, and a complex of the siRNA and the nano-particles is obtained by a double emulsification method, so that the small interfering RNA drug is obtained. The invention can prepare the nano-particles which can efficiently combine with siRNA, and reduce the minimum NP ratio required by the complete combination of siRNA and nano-particles. Moreover, the small interfering RNA drug can effectively enter cells, effectively silence the expression of pathogenic target genes, and inhibit the growth of breast cancer in vivo. Therefore, the drug delivery system has good prospect in the drug delivery of siRNA and similar small nucleic acid drugs for treating diseases.
Patients receive adavosertib PO QD on days 1, 3, and 5 or 1-5 weekly, and temozolomide PO QD on days 1-5. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
Participants will attend group sessions with a trained facilitator held over videoconference. Sessions will each last 2 hours and be held once weekly for 10 weeks. Sessions will include stress management skills training and health education content.
PROBLEM TO BE SOLVED: To obtain a topical cosmetic compositions for reducing or preventing signs of cellulite containing inositol phosphate as an active ingredient and a carrier thereby increasing the strength and the firmness of the dermic layer and the epidermal layer. SOLUTION: A cosmetic composition containing about 0.5 to 30 wt.% of inositol phosphate and 70-99.9 wt.% of a cosmetically acceptable carrier is topically applied to the skin to reduce or prevent the sign of cellulite. The inositol phosphate is preferably phytic acid. Particularly, a water-soluble salt as alkali metal, alkaline earth metal, ammonium or a 2-12C alkanol ammonium phytate is suitable. According to this method, the collagen synthesis in the skin can be increased. In this treatment, xanthine or an α-hydroxyacid can be applied to the skin.
The present invention relates to the prevention and/or the treatment of a disease associated with altered autophagy and/or Shh transduction, such as a cancer, an immune disease, an infectious disease, a metabolic disease, a cardiovascular disease, a (cardio)myopathy, heart failure, a lysosomal disease, spinal cord injury and trauma, a neurodegenerative disease and a pulmonary disease. The inventors showed that Gigaxonin promotes the fine-tuning of autophagy, by the means of its interaction with ATG16L1. In particular, cells depleted of Gigaxonin (GAN -/- neurons) exhibit ATG16L1 aggregation and a reduced capacity to produce autophagosomes, whereas overexpression of Gigaxonin rescues ATG16L1 aggregation and restores autophagy flux in GAN -/- neurons. The inventors also demonstrate that Gigaxonin is a key positive regulator of the Shh pathway, enabling receiving cells to convey signaling into motility. In particular, Gigaxonin depletion inhibits Shh transduction in the gan zebrafish model and patient cells, through a mechanism involving the interaction and degradation of the PTCH receptor. This pinpoints to an evolutionary-conserved and reversible mechanism that controls the entry point of Shh signalling and to the developmental origin of GAN. Thus, the present invention relates to a modulator of the expression, stability, degradation and/or activity of Gigaxonin, of the Gigaxonin/ATG16L1 or PTCH interaction and/or of the functionality of the Gigaxonin/ATG16L1 or PTCH interaction, for the prevention and/or the treatment of a disease associated with altered autophagy, Shh signaling and/or neurodegenerative disease.
The present invention relates to a novel mechanism for controlling RNA virus replication and gene expression using a conditional protease approach that is modulated using specific protease inhibitors. More specifically, it relates to single-stranded RNA viruses, preferably single-stranded RNA viruses of the order mononegavirales, comprising a polynucleotide sequence encoding at least one protein necessary for transcription and/or replication of the virus, a protease and a cleavage site for said protease. Protease inhibitors can be used to inhibit proteases, so that the protease and the cleavage site of the protease form a regulatable switch. The effect of the protease inhibitor may be changed from an ON switch to an OFF switch by changing the insertion site of the adjustable switch from an intramolecular position to an intermolecular position in at least one protein necessary for viral transcription and/or replication. RNA viruses can also encode heterologous proteins, the expression of which is then regulated by modulating viral activity. ON switches can also be used in RNA viruses to directly regulate heterologous protein expression. In vivo and in vitro uses of the viruses with conditional viral activity or heterologous protein expression are also provided.
PURPOSE: A composition containing Oenanthe javanica(BLUME.) extract and a method for preparing the same are provided to prevent and relieve fatty liver. CONSTITUTION: A method for preparing a composition containing OENANTHE javanica(BLUME.) extract for relieving fatty liver comprises: a step of drying and pulverizing whole plant or upper part of Oenanthe javanica(BLUME.); a step of adding extraction solvent and refluxing; and a step of filtering or concentrating the extract. The extraction solvent includes water or low carbon number alcohol of 1-4 carbon atoms.
The recognition that DNA can be ADP ribosylated provides an unexpected regulatory level of how ADP-ribosylation contributes to genome stability, epigenetics and immunity. Yet, it remains unknown whether DNA ADP-ribosylation (DNA-ADPr) promotes genome stability and how it is regulated. Here, we show that telomeres are subject to DNA-ADPr catalyzed by PARP1 and removed by TARG1. Mechanistically, we show that DNA-ADPr is coupled to lagging telomere DNA strand synthesis, forming at single-stranded DNA present at unligated Okazaki fragments and on the 3' single-stranded telomere overhang. Persistent DNA-linked ADPr, due to TARG1 deficiency, eventually leads to telomere shortening. Furthermore, using the bacterial DNA ADP-ribosyl-transferase toxin to modify DNA at telomeres directly, we demonstrate that unhydrolyzed DNA-linked ADP-ribose compromises telomere replication and telomere integrity. Thus, by identifying telomeres as chromosomal targets of PARP1 and TARG1-regulated DNA-ADPr, whose deregulation compromises telomere replication and integrity, our study highlights and establishes the critical importance of controlling DNA-ADPr turnover for sustained genome stability.
Passive leg raising (PLR) test is used to predict fluid responsiveness, which is performed by raising the legs of the patient to 45°. Cardiac output will be collected from both PAC and LiDCO before and after PLR.
Existing tools for predicting postoperative complications in women undergoing surgery for gynecological neoplasms are evaluated in this narrative review. Although surgery is a very efficient therapy for gynecological tumors, it is not devoid of the possibility of negative postoperative outcomes. Widely used tools at present, such as the Surgical Apgar Score and the Modified Frailty Index, fail to consider the complex characteristics of gynecological malignancies and their related risk factors. A thorough search of the PubMed database was conducted for our review, specifically targeting studies that investigate several aspects impacting postoperative outcomes, including nutritional status, obesity, albumin levels, sodium levels, fluid management, and psychological well-being. Research has shown that both malnutrition and obesity have a substantial impact on postoperative mortality and morbidity. Diminished sodium and albumin levels together with compromised psychological well-being can serve as reliable indicators of negative consequences. The role of appropriate fluid management in enhancing patient recovery was also investigated. The evidence indicates that although current mechanisms are useful, they have limitations in terms of their range and do not thoroughly address these recently identified risk factors. Therefore, there is a need for a new, more comprehensive tool that combines these developing elements to more accurately forecast postoperative problems and enhance patient results in gynecological oncology. This paper highlights the need to create such a tool to improve clinical practice and the treatment of patients.
The invention relates to a skin-whitening chloasma-reducing skin-brightening composition comprising raw materials of, by weight: 0.5 to 20 parts of nicotinamide, 0.1 to 15 parts of L-ascorbic acid 2-glucoside, 0.1 to 10 parts of an yeast extract, 0.05 to 10 parts of sodium lactate/sodium gluconate, 0.01 to 3.5 parts of sodium hydroxide, and 10 to 60 parts of water. With the composition provided by the invention, appearing and transferring of skin melanin can be inhibited or prevented from various perspectives; skin collagen protein synthesizing can be promoted, skin nutrients can be supplemented, such that skin aging can be retarded; and whitening effects can be achieved rapidly. Whitening active components are likely to be decomposed, oxidized, and discolored. With the composition, the problems can be solved; influences of lights and heat on the effective components are reduced. The product produced by the invention is safer than other whitening agents. With the product produced by the invention, nutrients required by skins can be provided. With a sustained-releasing technology, the whitening effect is more durable.
AAs in South Carolina bear an unequal burden of cancer incidence and mortality compared to their European American counterparts. The Research Program (RP) is committed to investigating and eliminating this burden through the careful conduct of research studies in partnership with their AA community partners. The overall aim of the RP is to support the SCCDCN-II in its mission to reduce, and ultimately eliminate, cancer health disparities using a community-based participatory research (CBPR) approach to design and conduct research projects in AA communities in South Carolina. The goals of the research program are to: support the SCCDCN by serving as a research liaison/consultant for all community-based activities; foster and support meaningful partnerships between academic researchers and community leaders and representatives; conduct a two-arm physical activity and dietary intervention trial for breast cancer prevention among African-American women in the investigators target communities of faith; conduct a pilot study to determine African-American men's and women's knowledge about prostate cancer screening and their knowledge and attitudes regarding participation in prostate cancer research, including National Cancer Institute (NCI) sponsored clinical trials; support additional research in cancer disparities through a Pilot Study post-transition year and to develop and implement an SCCDCN-II internal pilot grants program in years 4 and 5; and partner with community representatives to disseminate program findings and to work with colleagues in the AC, and Community Outreach and Training Programs to develop community capacity aimed at sustaining programs to improve health The two-arm intervention trial will be aimed at testing the effectiveness of a community-designed, family-based dietary and PA behavioral intervention on modifying biomarkers of inflammation and decreasing breast density with a randomized controlled design. The prostate cancer pilot will be aimed at assessing current knowledge and attitudes regarding prostate cancer prevention and screening, and participation in prostate cancer research; changes in knowledge and attitudes about research participation following a pilot education program; and culturally appropriate strategies for promoting cancer research among AAs in a faith-based community. All activities of the research program will be conducted in partnership with identified SCCDCN II community partners, the State Baptist YWA of the Women's BEMC, SCPHCA, CCBHSN, and Insights Consulting. It is anticipated that research activities will be conducted in all 5 years of the granting period with opportunities for research partnerships in all State Baptist YWA regions throughout the state.
The invention discloses a traditional Chinese medicine composition for treating the alcoholic liver. The traditional Chinese medicine composition for treating the alcoholic liver comprises eclipta alba, corn stigmas, mysore thorn roots, homelockleaved moonwort, tung tree fruits, spina gleditsiae, pteris cretica, polygonum multiflorum, curcuma aromatica, pseudobulbus calanthes fimbriatae, fimbriate calanthe pseudobulb, tarragon, butterflybush flowers, lalang grass rhizome, pluchea indica, fleshy spurge leaves and bamboo leaves. The traditional Chinese medicine composition nurses the health of a patient according to the root cause determined by a traditional Chinese physician for the alcoholic liver, and therapeutic principles are clear; medicines for conditioning the spleen, the liver, the stomach and the like are used for reasonable compatibility so that the effect of treating the spleen-deficiency and qi-stagnation reflux esophagitis can be realized. The traditional Chinese medicine composition is special for treating the alcoholic liver, is safe during clinical application and does not stimulate the viscera when taken. By means of the reasonable compatibility of all the components, the treatment effect is effectively improved, the drug properties are changed or relieved, and the toxicity and side effects of the medicines are eliminated. The treatment period is short and the treatment effect is remarkable. Clinical application studies show that the cure rate of the traditional Chinese medicine composition for the alcoholic liver reaches 95% and the total effective rate reaches 99%.
Although there is no clinical experience with the use of Butorphanol Tartrate Nasal Spray in nursing mothers, butorphanol has been detected in milk following administration of butorphanol tartrate injection to nursing mothers. The amount an infant would receive is probably clinically insignificant (estimated 4 mcg/L of milk in a mother receiving 2 mg IM four times a day). It should be assumed that butorphanol will appear in the milk in similar amounts following the nasal route of administration. 

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Butorphanol Tartrate Nasal Spray and any potential adverse effects on the breastfed infant from butorphanol or from the underlying maternal condition. 

Infants exposed to Butorphanol Tartrate Nasal Spray through breast milk should be monitored for excess sedation and respiratory depression. Withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped.
Religiosity and spirituality are fundamental aspects of the human experience, shaping beliefs, values, and how individuals navigate life's challenges. Religiosity refers to the degree to which individuals identify with, and participate in the practices and beliefs of, a particular religion. It encompasses behaviors like prayer, attending religious services, and following religious teachings. Spirituality, on the other hand, is a broader concept that reflects a sense of connection to something larger than oneself, a search for meaning and purpose in life. This connection can be expressed through religious beliefs, but it can also be independent of religion, encompassing a connection to nature, humanity, or a sense of purpose. Research has increasingly explored the complex interplay between these constructs and mental health. The relationship between religiosity/spirituality and mental health is multifaceted. Religious involvement can provide individuals with social support, a sense of belonging, and a framework for coping with stress. Spiritual beliefs can offer comfort, hope, and a sense of purpose, potentially promoting resilience in the face of challenges. However, the relationship is not always straightforward. Certain religious beliefs or practices could contribute to feelings of guilt, shame, or isolation, potentially impacting mental health. Additionally, negative religious coping styles, such as feeling angry or abandoned by God, might exacerbate mental health problems. Given the centrality of religion in the Arab world, including Egypt, a deeper look into the associations between religiosity/spirituality and psychiatric disorders such as depression and anxiety is warranted.
Serious adverse reactions including fatal reactions and the “gasping syndrome” occurred in premature neonates and low-birth weight infants who received benzyl alcohol dosages of 99 to 234 mg/kg/day (blood levels of benzyl alcohol were 0.61 to 1.378 mmol/L). Symptoms associated with “gasping syndrome” and other potential adverse reactions include gradual neurological deterioration, seizures, intracranial hemorrhage, hematological abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse. Premature neonates and low-birth weight may be more likely to develop these reactions because they may be less able to metabolize benzyl alcohol. The minimum amount of benzyl alcohol at which toxicity may occur is not known. Mesna injection contains 10.4 mg/mL of the preservative benzyl alcohol. Avoid use of mesna in premature neonates and low-birth weight infants. MESNEX tablets do not contain benzyl alcohol [See Use in Specific Populations (8.4)].
Patients will be instructed to start the treatment after two weeks from the day which consent was signed and for a duration of two weeks in wait-list control group. A follow-up visit will be on week 2 for a mid-term review and for the dispense of treating material.
Deployment of the tear gas agent 2-chlorobenzalmalononitrile (CS) for riot control has significantly increased in recent years. The effects of CS have been believed to be transient and benign. However, CS induces severe pain, blepharospasm, lachrymation, airway obstruction, and skin blisters. Frequent injuries and hospitalizations have been reported after exposure. We have identified the sensory neuronal ion channel, transient receptor potential ankyrin 1 (TRPA1), as a key CS target resulting in acute irritation and pain and also as a mediator of neurogenic inflammation. Here, we examined the effects of pharmacologic TRPA1 inhibition on CS-induced cutaneous injury. We modeled CS-induced cutaneous injury by applying 10 μl CS agent [200 mM in dimethyl sulfoxide (DMSO)] to each side of the right ears of 8- to 9-week-old C57BL/6 male mice, whereas left ears were applied with solvent only (DMSO). The TRPA1 inhibitor HC-030031 or A-967079 was administered after CS exposure. CS exposure induced strong tissue swelling, plasma extravasation, and a dramatic increase in inflammatory cytokine levels in the mouse ear skin. We also showed that the effects of CS were not transient but caused persistent skin injuries. These injury parameters were reduced with TRPA1 inhibitor treatment. Further, we tested the pharmacologic activity of advanced TRPA1 antagonists in vitro. Our findings showed that TRPA1 is a crucial mediator of CS-induced nociception and tissue injury and that TRPA1 inhibitors are effective countermeasures that reduce key injury parameters when administered after exposure. Additional therapeutic efficacy studies with advanced TRPA1 antagonists and decontamination strategies are warranted. SIGNIFICANCE STATEMENT: 2-Chlorobenzalmalononitrile (CS) tear gas agent has been deployed as a crowd dispersion chemical agent in recent times. Exposure to CS tear gas agents has been believed to cause transient acute toxic effects that are minimal at most. Here we found that CS tear gas exposure causes both acute and persistent skin injuries and that treatment with transient receptor potential ion channel ankyrin 1 (TRPA1) antagonists ameliorated skin injuries.