anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
TBX3 behaves as a tumor suppressor or oncoprotein across cancer. However, TBX3 function remains undetermined in intrahepatic cholangiocarcinoma (iCCA), a deadly primary liver malignancy with few systemic treatment options. This study sought to investigate the impact of TBX3 on iCCA. We found that overexpression of TBX3 strongly inhibited human iCCA cell growth. In the Akt/FBXW7ΔF mouse iCCA model, overexpression of Tbx3 reduced cholangiocarcinogenesis in vivo, while inducible genetic knockout of Tbx3 accelerated iCCA growth. RNA-seq identified MAD2L1 as a downregulated gene in TBX3-overexpressing cells, and ChIP confirmed that TBX3 binds to the MAD2L1 promoter. CRISPR-mediated knockdown of Mad2l1 significantly reduced the growth of two iCCA models in vivo. Finally, we found that TBX3 expression is upregulated in ~20% of human iCCA samples, and its high expression is associated with less proliferation and better survival. MAD2L1 expression is upregulated in most human iCCA samples and negatively correlated with TBX3 expression. Altogether, our findings suggest that overexpression of TBX3 suppresses CCA progression via repressing MAD2L1 expression.
Reflecting the lack of standardized methods or benchmarks for tactile technologies, the known limits of tactile sensitivity was narrowed from millimeters, microns, to nanometers within the last 10 years by use of metal wires, wrinkled plastics, and silanes, respectively. Investigators will determine the optimal design of traditional bumps which yields the highest tactile stimulus in the smallest area. Investigators expect to find that current bumps are larger than necessary, and that the same information could be placed into a smaller area (higher information density). Then, investigators will augment bumps with designer materials to increase the tactile stimulus from a bump, thereby permitting even smaller bumps to increase information density. Beyond optimal design methods, the investigators' quantitative methods, enabled by making the mechanical stimulus the dependent variable, also serve as benchmarks between tactile aids.
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease of the airways and lungs that develops against harmful particles or gases with exacerbations. COPD exacerbations are characterized by worsening of dyspnea, coughing and expectoration. Exacerbations requiring hospitalization are the main cause of morbidity and mortality in COPD. Bronchiectasis is the irreversible extension of the bronchi. Usually follows with chronic sputum cough, airway obstruction and recurrent infection episodes. The association of bronchiectasis and COPD has long been known and its incidence is in the range of 30-50%. Coexistence of bronchiectasis with COPD may lead to worsening of the functional parameters as well as alteration of the microbiological pattern in exacerbations and may negatively affect the exacerbation result parameters.
When RISPERDAL® is co-administered with enzyme inducers (e.g., carbamazepine), the dose of RISPERDAL® should be increased up to double the patient's usual dose. It may be necessary to decrease the RISPERDAL® dose when enzyme inducers such as carbamazepine are discontinued [see Drug Interactions (7.1)]. Similar effect may be expected with co-administration of RISPERDAL® with other enzyme inducers (e.g., phenytoin, rifampin, and phenobarbital).

When fluoxetine or paroxetine is co-administered with RISPERDAL®, the dose of RISPERDAL® should be reduced. The RISPERDAL® dose should not exceed 8 mg per day in adults when co-administered with these drugs. When initiating therapy, RISPERDAL® should be titrated slowly. It may be necessary to increase the RISPERDAL® dose when enzyme inhibitors such as fluoxetine or paroxetine are discontinued [see Drug Interactions (7.1)].
Risk Summary

Based on findings from animal studies and its mechanism of action [see Clinical Pharmacology (12.1)], sorafenib may cause fetal harm when administered to a pregnant woman. There are no available data in pregnant women to inform a drug-associated risk. In animal reproduction studies, oral administration of sorafenib to pregnant rats and rabbits during the period of organogenesis resulted in embryo-fetal toxicities at maternal exposures that were significantly lower than human exposures at the recommended dose of 400 mg twice daily (see Data). Advise pregnant women and females of reproductive potential of the potential risk to a fetus.

The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data

Animal Data

In animal reproduction studies, sorafenib was teratogenic and induced embryo-fetal toxicity (including increased post-implantation loss, resorptions, skeletal retardations, and retarded fetal weight) when administered orally to pregnant rats and rabbits during the period of organogenesis. The effects occurred at doses considerably below the recommended human dose of 400 mg twice daily (approximately 500 mg/m2/day on a body surface area basis). Adverse intrauterine development effects were seen at doses >0.2 .mg/kg/day (1.2 mg/m2/day) in rats and ≥0.3 mg/kg/day (≥3.6 mg/m2/day) in rabbits. These doses result in exposures (AUC) that are approximately 0.008 times the AUC in patients at the recommended dose.
This was a Phase 2b, multi-center, randomized, double-blind, vehicle-controlled study to assess the efficacy and safety of SD-101 dermal cream (3% or 6%) on skin lesions in participants with Simplex, Recessive Dystrophic, or Junctional non-Herlitz EB.

SD-101 cream \[containing 3% or 6% or vehicle (0%)\] was applied topically, once a day to the entire body for a period of 90 days. Eligible participants had a target wound assessed at baseline. Selected target wound had to be at least a certain age and within a prespecified size range at study entry. Photographic confirmation of the target wound location was collected at baseline, and the picture saved from the first visit was used to confirm location of the target wound at subsequent visits. The participant returned to the study site at Week 2, Month 1, Month 4, and Month 5 (at 14, 30, 60, and 90 days, respectively) to have the target wound previously identified at baseline re-assessed for the level of healing. In addition, changes in itching, pain, body surface area coverage of blisters and lesions, and scaring of the healed target wound were also assessed at each visit.
Postoperative neurocognitive disorders (PND) are the most common neurological disorders following surgery and anaesthesia before and within 12 months after surgery, with a high prevalence in the geriatric population. PND can severely deteriorate the quality of life of patients, especially among the elderly, mainly manifested as memory loss, attention, decline and language comprehension disorders, mostly in elderly patients, with an incidence as high as 31%. Previous studies have also raised the possibility of accelerated cognitive decline and underlying neuropathological processes associated with diseases that affect cognitive performance (e.g. Alzheimer's dementia) for reasons related to anaesthesia and surgery. Currently, most research on PND has focused on various molecular pathways, especially in the geriatric population. The various hypotheses that have been proposed regarding the mechanisms imply peripheral neuroinflammation, oxidative stress, mitochondrial homeostasis, synaptic function, autophagy disorder, blood-brain barrier dysfunction, the microbiota-gut-brain axis and lack of neurotrophic support. However, the underlying pathogenesis and molecular mechanisms of PND have not yet been uncovered. Recent research has focused on mitochondrial homeostasis. In this paper, we present a review of various studies to better understand and characterize the mechanisms of associated cognitive dysfunction. As the biochemical basis of PND becomes more clearly defined, future treatments based on mitochondrial homeostasis modulation can prove to be very promising.
The invention belongs to the field of traditional Chinese medicine, and discloses a traditional Chinese medicine composition for healing a haemorrhoid postoperative wound and a preparation method thereof. The traditional Chinese medicine composition is composed of medicine for oral administration and medicine for external use. The medicine for oral administration is prepared from the root of clerodendron bungei steud, sheepear inula herb, gymnadnia conopsear broyn, herb of white clover, the root of bidentate achyranthes, safflower carthamus, peach kernels, elecampane and gallnuts. The medicine for external use is prepared from peperomia blanda, borneol, cutch, dragon's blood, golden cypress, field pennycress and Chinese violet. The medicine for oral administration has the effects of promoting blood circulation to remove blood stasis, inducing diuresis and reducing edema, and stopping bleeding and relieving pain. The medicine for external use has the effects of dispelling dampness and resolving toxin, promoting blood circulation to remove blood stasis, and relieving swelling and pain. According to the traditional Chinese medicine composition, by combining oral administration and external use, local circulation can be improved, tissue nutrition can be added, granulation growth is accelerated, and therefore the effect of healing the postoperative wound as soon as possible is achieved; both haemorrhoid causes and haemorrhoid postoperative pathological changes are considered, and the effect is remarkable.
AIMS: Lesbian, gay, bisexual, transgender and other people (LGBT+) individuals may have a greater risk of experiencing mental and physical health issues. In the past years, the predominant theme of research was HIV/AIDS and sexually transmitted infections (STIs). This study aimed to explore the most recent patterns in medical research concerning LGBT+ persons.
METHODS: A bibliometric analysis using Biblioshiny was conducted. Based on previous studies, years of observation ranged between 2008 and 2021. Web of Science Core Collection was used.
RESULTS: A total of 31,039 articles were selected. Top journals centered around HIV/AIDS and STIs (n = 6), followed by sexual behaviors/sexuality (n = 2) and LGBT+ health (n = 2). The US led in research output (n = 16,249). Papers were categorized into three main clusters (which showed different evolution across time): one addressing HIV/AIDS, STIs, and sexual behaviors, another focusing on mental health, discrimination, and stigma, and a third, smaller cluster examining transgender, intersex, and gender-diverse health.
CONCLUSIONS: This article highlighted a growth in LGBT+ health research, uncovering research disparities among countries. While HIV/AIDS and STIs still dominated, a crucial theme concerning mental health, discrimination, and stigma has been rising. Declining interest in gender-diverse health, and disparities in research attention to different LGBT+ subgroups, underscored the need for more comprehensive and inclusive research to address complex health disparities.
ABSTRACT OF THE DISCLOSURE             The present invention relates to a method which eliminates centrifugation and decantation steps, to be performed in an automatic manner for carrying out specific binding assay tests, wherein liquid and solid phases are present.           According to the invention, use is made of a specially designed device, consisting of a mixing reservoir into which is fitted snugly a mixer separator having a channel in the vertical axis of the mixer-separator.  A rack holding a number of said mixing reservoirs containing the incubated reagents and analytes, capped with the mixer separators, is placed into a press-device designed to perform at a controlled rate a downward movement.  The mixer separators are pushed downwards into the mixing reservoirs at a chosen rate for a preselected distance to complete the mass transport and separation operation.  The separation devices are removed and either one of the separated phases can be measured in the desired analytical instrument for a quantitative or qualitative determination.           The results obtained according to the present invention compare very favourably with those determined by other methods requiring centrifugation and/or decantation in the assay protocol.
The invention relates to a troche for enhancing bone mineral density based on milk mineral salt as a raw material. Most calcium tablets are poor in taste and unsatisfactory in effect. Therefore, the troche provided by the invention is prepared by milk mineral salt, vitamin D3, casein phosphopeptides, whole milk powder, mannite, sodium carboxymethylcellulose and magnesium stearate. The invention further relates to a preparation method of the troche for enhancing bone mineral density based on milk mineral salt as the raw material. The troche for enhancing bone mineral density based on milk mineral salt as the raw material provided by the invention has various functions of milk mineral salt, vitamin D3, casein phosphopeptides and whole milk powder, and the bone density of users is increased. The troche is better in taste, smaller in use level and free from dependency, so that the troche is suitable for various crowds except infants.
PURPOSE: Epigenetic dysregulation has been associated with many inherited disorders. RBBP5 (HGNC:9888) encodes a core member of the protein complex that methylates histone 3 lysine-4 and has not been implicated in human disease.
METHODS: We identify 5 unrelated individuals with de novo heterozygous variants in RBBP5. Three nonsense/frameshift and 2 missense variants were identified in probands with neurodevelopmental symptoms, including global developmental delay, intellectual disability, microcephaly, and short stature. Here, we investigate the pathogenicity of the variants through protein structural analysis and transgenic Drosophila models.
RESULTS: Both missense p.(T232I) and p.(E296D) variants affect evolutionarily conserved amino acids located at the interface between RBBP5 and the nucleosome. In Drosophila, overexpression analysis identifies partial loss-of-function mechanisms when the variants are expressed using the fly Rbbp5 or human RBBP5 cDNA. Loss of Rbbp5 leads to a reduction in brain size. The human reference or variant transgenes fail to rescue this loss and expression of either missense variant in an Rbbp5 null background results in a less severe microcephaly phenotype than the human reference, indicating both missense variants are partial loss-of-function alleles.
CONCLUSION: Haploinsufficiency of RBBP5 observed through de novo null and hypomorphic loss-of-function variants is associated with a syndromic neurodevelopmental disorder.
A gastrin analogue shows high uptake in CCK-2 receptor positive tumors and simultaneously a very low accumulation in the kidneys. This is achieved by a mini-gastrin analogue PP-F11 having the formula: PP-F11-X-DGlu-DGlu-DGlu-DGlu-DGlu-DGlu-Ala-Tyr-Gly-Trp-Y-Asp-Phe-NH2, wherein Y is an amino acid replacing methionine and X is a chemical group attached to the peptide for diagnostic and/or therapeutic intervention at CCK-2 receptor relevant diseases. Very suitable compounds with respect to a high tumor to kidney ratio are mini-gastrin analogues with six D-glutamic acids or six glutamines. These compounds still possess a methionine which can be oxidized easily which is a disadvantage for clinical application under GMP due to the forms which may occur. The elimination of the methionine leads to a lower affinity to oxidation which in general favors the tumor-kidney-ratio. Ideally, the methionine is replaced by norleucine. This PP-F11N mini gastrin exhibits currently the best tumor-kidney-ratio and is the most promising candidate.
BACKGROUND: Burnout is a condition characterized by emotional exhaustion, low personal accomplishment, and feelings of depersonalization that may evolve as a result of chronic occupational stress. Our goal for the study was to measure the degree of burnout among US dental school faculty with less than 10 years in academia.
MATERIALS AND METHODS: A mixed method approach to data collection was utilized for the study and included: A. A 15-items demographics survey B. Maslach Burnout Inventory (MBI) combined with the Area-Work life Scale (AWS) C. A survey open-ended response to respondent's general feelings about work environment.
RESULTS: MBI results from the data collected from 52 respondents indicate 7 or 13.46% of respondents are categorized with a 'burnout' profile. The most abundant categories recognized among this group are feelings of being "overextended" (34.62%) while 32.69% of the respondents self-report signs of being engaged. The results from this population indicate higher emotional exhaustion while levels of depersonalization are lower. The Area-Work life Scale (AWS) for this group indicates a higher sense of reward and control, while a lower frequency of workload balance and fairness are recognized. The data collected from the sample population suggest increased higher feelings of burnout at the 9-year mark, with increased administrative duties, and age range over 44 years.
CONCLUSION: Identifying factors in workload, work environment, and influences in the home that lead to burnout early in a faculty member's tenure and introducing reduction mechanisms are key to enhancing faculty production, satisfaction, and retention.
Compositions containing a tissue plasminogen activator (t-PA), epidermal growth factor (EGF), transforming growth factor-alpha (TGF alpha ), transforming growth factor-beta (TGF- beta ), human endothelial cell growth factor (ECGF), granulocyte macrophage colony stimulating factor (GM-CSF) and a fibronectin or large external transformation sensitive protein (LETS) including cell surface protein (CSP), cell adhesion protein (CAP), cell insoluble globulin (CIG) and/or opsonic-alpha 2 surface binding glycoprotein in a suitable physiologically acceptable carrier are useful for the treatment of humans when topically and/or subcutaneously applied. These compositions might also usefully contain or have employed in association therewith an adjuvant to aid in the transdermal transport or transfer of the compositions, particularly the active components therein, through or across the skin. Also, these compositions might also have contained therein or employed in association therewith an antiviral agent, such as an antiviral surfactant, for example, an antiviral nonionic surfactant, e.g. nonylphenoxypolyethoxy ethanol and/or human interferon, e.g. alpha-interferon. Additionally, these compositions might contain or have employed in association therewith an antitumor agent, such as tumor necrosis factor (TNF), target cell lysis factor (TCLF) and carcino-breaking factor (CBF). These compositions are useful in the treatment or healing of humans, e.g. in the treatment of viral and/or cancerous skin disorders or lesions and/or to expedite healing.
The gray mold fungus Botrytis cinerea is a necrotrophic pathogen that causes diseases in hundreds of plant species, including high-value crops. Its polyxenous nature and pathogenic success are due to its ability to perceive host signals in its favor. In this study, we found that laticifer cells of Euphorbia lathyris are a source of susceptibility factors required by B. cinerea to cause disease. Consequently, poor-in-latex (pil) mutants, which lack laticifer cells, show full resistance to this pathogen, whereas lot-of-latex mutants, which produce more laticifer cells, are hypersusceptible. These S factors are triterpenoid saponins, which are widely distributed natural products of vast structural diversity. The downregulation of laticifer-specific oxydosqualene cyclase genes, which encode the first committed step enzymes for triterpene and, therefore, saponin biosynthesis, conferred disease resistance to B. cinerea. Likewise, the Medicago truncatula lha-1 mutant, compromised in triterpenoid saponin biosynthesis, showed enhanced resistance. Interestingly, the application of different purified triterpenoid saponins pharmacologically complemented the disease-resistant phenotype of pil and hla-1 mutants and enhanced disease susceptibility in different plant species. We found that triterpenoid saponins function as plant cues that signal transcriptional reprogramming in B. cinerea, leading to a change in its growth habit and infection strategy, culminating in the abundant formation of infection cushions, the multicellular appressoria apparatus dedicated to plant penetration and biomass destruction in B. cinerea. Taken together, these results provide an explanation for how plant triterpenoid saponins function as disease susceptibility factors to promote B. cinerea pathogenicity.
Patients will receive IMTOX25 at 2mg/m²/dose, by IV administration, every other day for a total of 3 doses. A total of 6 cycles of treatment will be allowed. A cycle is equal to 6 weeks, with IMTOX25 infusion on Day 1, 3 and 5, followed by a 5 week rest period.
Patients will be randomized to receive a one-time dose of intrathecal hydromorphone or intrathecal morphine as part of their spinal anesthesia. The starting dose of intrathecal hydromorphone will be 40 micrograms. This will be adjusted in subsequent patients based on the previous patient's success or failure according to an up-and-down methodology utilizing a biased coin design.
Many adolescents and young adults living with chronic health conditions lack knowledge about their medical condition and confidence communicating with health care providers. Despite various positions statements on transition by the Canadian Pediatric Society, the American Academy of Pediatrics and the American Heart Association, there is limited evidence on the impact and effectiveness of transition interventions. Due to the convenience and accessibility of technology, adolescents embrace technology-based interventions to aid in their disease management and to improve their transition experience. However, there is a paucity of evidence-based apps in contrast to countless existing apps that are not evidence-based, which act as a barrier to physicians prescribing them. There is a pressing need for credible evidence on the effectiveness and value of health apps in improving self-management skills in adolescents.

Instead of redesigning a mobile app, the Just TRAC It! encourages youth to use existing functions on their personal phones to track their health information. This information is easily retrievable when visiting health care providers and can help youth take ownership in managing their own health. This free option, using the technology already on most phones, can be used for any patient population or disease category. The use of Just TRAC It! allows youth to electronically document all medical information that would previously be printed on their MyHealth Passport, but may offer additional functionality in terms of learning to manage their health. Further investigation is warranted to evaluate the effectiveness of Just TRAC It! on improving patient knowledge, self-management skills, and transition readiness.

The Stollery Children's Hospital is an international leader in pediatric to adult cardiology transition research, with two randomized clinical trials completed (CHAPTER 1 Trial, Mackie et al, Heart 2014 and CHAPTER 2 Trial, Mackie et al, BMC Cardiovascular 2016) and a 3rd in progress. The Just Trac It! Trial is an extension of our prior work. The results of the CHAPTER 1 Trial inform the current standard of care for transition interventions currently offered to all 16-18 year olds in our program who have had prior cardiac surgery, and this standard of care is the "usual care" (control) group for the Just Trac It! Study.