anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Carcinogenicity studies have not been conducted with lenvatinib. Lenvatinib mesylate was not mutagenic in the in vitro bacterial reverse mutation (Ames) assay. Lenvatinib was not clastogenic in the in vitro mouse lymphoma thymidine kinase assay or the in vivo rat micronucleus assay.

No specific studies with lenvatinib have been conducted in animals to evaluate the effect on fertility; however, results from general toxicology studies in rats, monkeys, and dogs suggest there is a potential for lenvatinib to impair fertility. Male dogs exhibited testicular hypocellularity of the seminiferous epithelium and desquamated seminiferous epithelial cells in the epididymides at lenvatinib exposures approximately 0.02 to 0.09 times the AUC at the recommended clinical dose of 24 mg once daily. Follicular atresia of the ovaries was observed in monkeys and rats at exposures 0.2 to 0.8 times and 10 to 44 times the AUC at the recommended clinical dose of 24 mg once daily, respectively. In addition, in monkeys, a decreased incidence of menstruation was reported at lenvatinib exposures lower than those observed in humans at the recommended clinical dose of 24 mg once daily.
PURPOSE: The role of topical vancomycin in fracture-related infection (FRI) is debatable. Very few studies have reported their efficacy in open and high-risk extremity fractures. This study aimed to assess topical vancomycin's role in reducing FRI in closed fractures undergoing open surgical intervention with an implant.
METHODS: This prospective randomized cohort study was carried out between February 2021 to January 2022. Patients with isolated closed fractures, who were planned for open reduction and internal fixation within 2 weeks from the time of injury were included for this study. The data collected included age, gender, socioeconomic status, mechanism of injury, diagnosis, Tscherne classification, and time interval to take up for surgery. Patients were randomized into the intervention and control groups using the block randomization technique. The control group received only systemic antibiotic prophylaxis, whereas the intervention group received topical application of vancomycin powder in the surgical wound alongside systemic antibiotic prophylaxis. The primary outcome measure was the incidence of FRI among these individuals. Clinical and radiological findings and culture reports (in cases with infection) were recorded during the post-operative period and at 6 weeks of follow-up. All relevant statistical calculations were done using STATA statistical/data analysis-parallel edition version 16.0 (StataCorp LLC). The quantitative variables like age and duration of the surgery were assessed for normalcy by Shapiro-Wilk W test. An independent samples t-test with equal variances was applied to the age data. Fisher's exact test was used for the analysis of the primary outcome measure (presence of FRI following surgery), and "Risk of FRI" and "Risk difference" between the 2 groups was calculated. The strength of the association between qualitative variables was assessed using the Fisher's exact and Chi-square tests, respectively.
RESULTS: There were 88 patients included in this study. No statistical significance was found about FRI between both groups (p = 0.494). At 6 weeks following surgery, no incidence of infection was observed in the intervention group. Two infections (4.5%) were found in the control group, with positive cultures reported in one of them but none in the treatment group. Radiologically, 15.9% of patients in the control group showed lysis around the implant compared to 2.3% in the intervention group. Impaired fracture healing was observed in 22.7% of patients in the intervention group compared to 15.9% in the control group.
CONCLUSION: Applying topical vancomycin in closed fractures undergoing open reduction and internal fixation does not significantly reduce the incidence of FRI until the end of 6 weeks following surgery.
To conduct a feasibility clinical trial to test a novel patient sensing automated treadmill device devised by local engineers for subacute hemiplegic stroke patients for gait rehabilitation. This device incorporates patient automated variable speeds and feedback, increased safety features with patient support harness and visual feedback providing ambulatory gait monitoring data. Methodology: 10 stable subacute hemiparetic stroke subjects will undergo supervised treadmill training using this device targeted at improving gait speed and walking independence. Outcomes will be measured at 4 time points pre and post training using clinical scales and temporal-spatial gait measurements. Importance of research to medicine: This study tests the possibility of patient initiated control and closed loop sensing feedback system to provide increased intensity, reduced risk of gait destabilisation and fall risk which are associated with current fixed treadmill training. Potential benefits with new device: Ability to train at self selected variable speeds including fast speeds, improved hemiplegic leg swing initiation and stride length, less assistance required from physiotherapist and reduced fall risk due to overhead safety harness and treadmill sensing and increased patient confidence. Possibility of ambulatory gait speed and force loading during treadmill training. Potential risks: Minor risks of fall are minimised as there is a safety harness and supervision by physiotherapist. Anticipated risks related to repetitive treadmill training with regards to cardiovascular and musculoskeletal side effects will be mitigated with strict patient inclusion and exclusion criteria.
Acebutolol is well absorbed from the GI tract. It is subject to extensive first-pass hepatic biotransformation, with an absolute bioavailability of approximately 40% for the parent compound. The major metabolite, an N-acetyl derivative (diacetolol), is pharmacologically active. This metabolite is equipotent to acebutolol and in cats is more cardioselective than acebutolol; therefore, this first-pass phenomenon does not attenuate the therapeutic effect of acebutolol. Food intake does not have a significant effect on the area under the plasma concentration-time curve (AUC) of acebutolol although the rate of absorption and peak concentration decreased slightly.

The plasma elimination half-life of acebutolol is approximately 3 to 4 hours, while that of its metabolite, diacetolol, is 8 to 13 hours. The time to reach peak concentration for acebutolol is 2.5 hours and for diacetolol, after oral administration of acebutolol, 3.5 hours.

Within the single oral dose range of 200 to 400 mg, the kinetics are dose proportional. However, this linearity is not seen at higher doses, probably due to saturation of hepatic biotransformation sites. In addition, after multiple dosing the lack of linearity is also seen by AUC increases of approximately 100% as compared to single oral dosing. Elimination via renal excretion is approximately 30% to 40% and by nonrenal mechanisms 50% to 60%, which includes excretion into the bile and direct passage through the intestinal wall.

Acebutolol has a low binding affinity for plasma proteins (about 26%). Acebutolol and its metabolite, diacetolol, are relatively hydrophilic and, therefore, only minimal quantities have been detected in the cerebrospinal fluid (CSF). 

Drug interaction studies with tolbutamide and warfarin indicated no influence on the therapeutic effects of these compounds. Digoxin and hydrochlorothiazide plasma levels were not affected by concomitant acebutolol administration. The kinetics of acebutolol were not significantly altered by concomitant administration of hydrochlorothiazide, hydralazine, sulfinpyrazone, or oral contraceptives.

In patients with renal impairment, there is no effect on the elimination half-life of acebutolol, but there is decreased elimination of the metabolite, diacetolol, resulting in a two- to three-fold increase in its half-life. For this reason, the drug should be administered with caution in patients with renal insufficiency (see PRECAUTIONS). Acebutolol and its major metabolite are dialyzable.

Acebutolol crosses the placental barrier and is secreted in breast milk.

In geriatric patients, the bioavailability of acebutolol and its metabolite is increased, approximately two-fold, probably due to decreases in the first-pass metabolism and renal function in the elderly.
OBJECTIVES: to evaluate inflammation and vascularization in a model of apical periodontitis in diabetic Wistar rats through histopathological examination of blood vessels and immunohistochemical examination of interleukin 1b (IL-1b) and tumor necrosis factor-a (TNF-a).
METHODOLOGY: Diabetes was induced in 20 Wistar rats using multiple low-dose injections of streptozotocin (STZ) until blood glucose levels stabilized above 300 mg/dL, confirmed by glucometer. Under anesthesia, apical periodontitis was induced in the right mandibular first molars. After preparing the access cavity and extirpating pulp and canal, the teeth were left open. Apical periodontitis was projected seven days afterwards and the Wistar rats were assigned in random into four groups, each group consisting of five rats. The first group (C14) was euthanized 14 days post-induction, while the second group (C28) was euthanized 28 days later, serving as controls. The third group (T14) received mesenchymal stem cells from human umbilical cords and was euthanized after 14 days, while the fourth group (T28) received mesenchymal stem cells from human umbilical cord and was euthanized after 28 days. The number of blood vessels and the expressions of IL-1b and TNF-a were analyzed. Data were evaluated with ANOVA and by Tukey's HSD test, with significance at p<0.05.
RESULTS: Both control and treatment groups showed a significant increase in vascularization in the apical periodontal area of apical periodontitis in the control and treatment groups at 14 and 28 days (p<0.05). A significant reduction of IL-1b and TNF-a levels was found in the mesenchymal stem cells treatment groups when compared to control groups (p<0.05).
CONCLUSION: Our findings support the use of mesenchymal stem cells from human umbilical cords to decrease inflammation and increase vascularization in an induced apical periodontitis model in diabetes mellitus Wistar rats.
FIELD: medicine.SUBSTANCE: invention refers to medicine, namely to ophthalmology. For ultraviolet (UV) cross-linking of the cornea with progressive keratectasia in the patients with developed far-reaching keratoconus and iatrogenic ectasia after refractive interventions preliminary revealing the most thin section of cornea according to patient's pachymetric chart and area of ectasia. De-epithelialisation of cornea in 8.5 mm zone, saturation of de-epithelised cornea and soft contact lens with 0.1 % aqueous solution of riboflavin. Riboflavin-saturated contact lens is then trepaned to produce a disc with diameter of 3–5 mm and thickness of 120 mcm, which is perforated. Thereafter, the disc is placed on the cornea so that its center coincides with the apex of the cone on the basis of the data of topographic pachymetry and keratotopography of the patient. Ultraviolet irradiation is performed capacity of 3 mW/cm2for 30 minutes, or 9 mW/cm2for 10 minutes, or 18 mW/cm2for 5 minutes.EFFECT: method provides a therapeutic effect and protection of deep layers of the cornea by local thickening in a zone of maximum thinning and distribution of radiation at the same depth throughout the entire surface of the cornea, access of oxygen to the cornea during the procedure, as well as possibility of the patients with a thin cornea treatment by the cross-linking method.1 cl, 3 ex
Many cancer-driving protein targets remain undruggable due to a lack of binding molecular scaffolds. In this regard, octahedral metal complexes with unique and versatile three-dimensional structures have rarely been explored as inhibitors of undruggable protein targets. Here, we describe antitumor iridium(III) pyridinium-N-heterocyclic carbene complex 1a, which profoundly reduces the viability of lung and breast cancer cells as well as cancer patient-derived organoids at low micromolar concentrations. Compound 1a effectively inhibits the growth of non-small-cell lung cancer and triple-negative breast cancer xenograft tumors, impedes the metastatic spread of breast cancer cells, and can be modified into an antibody-drug conjugate payload to achieve precise tumor delivery in mice. Identified by thermal proteome profiling, an important molecular target of 1a in cellulo is Girdin, a multifunctional adaptor protein that is overexpressed in cancer cells and unequivocally serves as a signaling hub for multiple pivotal oncogenic pathways. However, specific small-molecule inhibitors of Girdin have not yet been developed. Notably, 1a exhibits high binding affinity to Girdin with a Kd of 1.3 μM and targets the Girdin-linked EGFR/AKT/mTOR/STAT3 cancer-driving pathway, inhibiting cancer cell proliferation and metastatic activity. Our study reveals a potent Girdin-targeting anticancer compound and demonstrates that octahedral metal complexes constitute an untapped library of small-molecule inhibitors that can fit into the ligand-binding pockets of key oncoproteins.
Chronic pain is the key manifestations of rheumatoid arthritis. Neuroinflammation in the spinal cord drives central sensitization and chronic pain. Ferroptosis has potentially important roles in the occurrence of neuroinflammation and chronic pain. In the current study, mouse model of collagen-induced arthritis was established by intradermal injection of type II collagen in complete Freund's adjuvant (CFA) solution. CFA inducement resulted in swollen paw and ankle, mechanical and spontaneous pain, and impaired motor coordination. The spinal inflammation was triggered, astrocytes were activated, and increased NLRP3-mediated inflammatory signal was found in CFA spinal cord. Oxidative stress and ferroptosis in the spinal cord were manifested. Meanwhile, enhancive spinal GSK-3β activity and abnormal phosphorylated Drp1 were observed. To investigate the potential therapeutic options for arthritic pain, mice were intraperitoneally injected with AB4 for three consecutive days. AB4 treatment reduced pain sensitivity and increased the motor coordination. In the spinal cord, AB4 treatment inhibited NLRP3 inflammasome-mediated inflammatory response, increased antioxidation, decreased mitochondrial reactive oxygen species and ferroptosis. Furthermore, AB4 decreased GSK-3β activity by binding with GSK-3β through five electrovalent bonds. Our findings indicated that AB treatment relieves arthritis pain by inhibiting GSK-3β activation, increasing antioxidant capability, reducing Drp1-mediated mitochondrial dysfunction and suppressing neuroinflammation.
Chimeric antigen receptor (CAR) T-cell therapy has demonstrated remarkable success in treating various B-cell malignancies, redirecting T-cell cytotoxicity toward cancer cells. Despite its efficacy, CAR-T therapy is associated with potential risks, including cytokine release syndrome (CRS) and cytopenia. We present a case of a 69-year-old man with diffuse large B-cell lymphoma treated with axicabtagene-ciloleucel CAR-T therapy, who developed a rare and severe cutaneous toxicity resembling toxic epidermal necrolysis (TEN). The patient exhibited persistent fevers, CRS, and subsequent development of a widespread erythematous macular eruption, progressing to vesiculation with bullae. Notably, allopurinol-induced TEN was considered with the patient's recent exposure to allopurinol, although the onset and minimal mucosal involvement did not align with typical presentations of allopurinol-induced cases. The cutaneous reaction, distinct from typical SJS/TEN, showed minimal mucosal involvement and coincided with the cytokine release storm, differing from allopurinol-induced TEN. Despite the absence of guidelines, the patient was managed with systemic steroids, achieving significant improvement. This case expands the spectrum of CAR-T therapy-related cutaneous toxicities, highlighting the need for early recognition of histopathology and tailored management by dermatologists. Further understanding of these reactions is crucial for optimizing the safety profile of this groundbreaking immunotherapy.
FIELD: medicine. SUBSTANCE: invention relates to conservative methods of treatment of trophic ulcers of venous genesis. Method involves applying on ulcer dialdehydecellulose-base napkins containing immobilized trypsin and 100 mg of mexidol. Additionally, mexidol is administrated by intramuscular route at the dose 100 ml per injection for 5 days. EFFECT: accelerated and simplified treatment of trophic ulcers. 1 tbl, 1 ex
Two major issues appear in improving the prognosis of cancer patients, the first is early detection and the second is the risk of recurrence or the early diagnosis of recurrence in order to propose the most appropriate treatment for patients.

Cancer is a DNA disease that is characterized by the acquisition by the tumor cell during carcinogenesis of a number of recurrent genetic alterations. The development of molecular tools that can easily characterize these abnormalities specific to tumor cells, allows us to consider their use in clinical practice. These genetic alterations could represent useful molecular markers for detecting the presence of tumor DNA in various biological fluids including plasma of cancer patients. This circulating tumor DNA, whose nature is confirmed by the similarity of genetic alterations with those observed from DNA extracted from tumor cells of the patients, represents a molecular marker of cancer available from a single sample and could be an alternative to the use of more conventional markers such as CEA. We propose in this study to confirm the predictive value on the risk of recurrence or metastasis of circulating tumor DNA in plasma of patients with colorectal cancer from a cohort study (250 patients with non-metastatic colorectal cancer (Stage II and III). This is a multicenter prospective study. The cohort of patients will be followed for a minimum period of 36 months. A biological analysis of the tumor in search for the main genetic alterations of colorectal cancer cells will be made (KRAS, NRAS, TP53, BRAF and APC mutations as well as the presence of a microsatellite instability). These same genetic alterations will be sought on a plasma sample taken before surgery and during follow-up (9 samples in total). The objectives of this study will be 1/to assess the prognostic value of the presence of circulating tumor DNA in plasma, by searching for an association between the risk of and the presence of genetic alteration in the plasma of these patients, 2/to search for a relationship between initial rate of circulating tumor DNA and the risk of local recurrence,3/ to characterize the relationship between the type of alterations in the plasma at the initial diagnosis of circulating tumor DNA and the risk of recurrence 4/ to assess during the follow-up the prognostic value of the occurrence of tumor circulating DNA.
The patients were asked to stretch for 20 s with the other hand with the shoulder in internal rotation, elbow in extension, forearm in pronation, wrist in flexion and ulnar deviation. In the first week, stretching exercises were recommended to be performed 3 sets a day, 5⨯20 s in one set and 45 s rest interval before strengthening exercises. The application will be performed with the thumb in the transverse direction, with the pressure tolerated by the individual, for 10 minutes after numbness is obtained, the treatment lasts approximately 10-15 minutes.
PCT No. PCT/US97/00370 Sec. 371 Date Apr. 13, 1998 Sec. 102(e) Date Apr. 13, 1998 PCT Filed Jan. 3, 1997 PCT Pub. No. WO97/25446 PCT Pub. Date Jul. 17, 1997A method for generating adenoviral vectors from polynucleotides such as plasmids wherein there occurs recombinase-mediated transfer of an adenoviral ITR and terminal proteins bound to the ITR to a plasmid, thus enabling the plasmid to replicate as an adenoviral vector. Such method enables the rapid generation of adenoviral vectors at high titers from plasmids without the use of selectable markers and screening procedures. Such method enables the rapid generation of adenoviral vectors devoid of adenovirus backbone genes. The method also may be employed to generate hybrid adenoviral-retroviral vectors that convert transduced cells into producer cells that produce retroviral vectors to effect high level, permanent genetic modification of cells in vivo.
Cognitive impairment (CI) is regarded as a remarkable burden in COVID-19 survivors. Its prevalence and profile, and relationships with the disease clinical and laboratory indices, remain unclear. The present study investigated, in a large sample of patients recovered from COVID-19, the frequency of CI with both a face-to-face screening tool and comprehensive test battery (MCCB). The study also evaluated the profile of CI and its relationships with COVID-19 clinical and laboratory indices and with psychopathological features. Out of 1344 subjects assessed for eligibility, 736 completed the screening phase 11 months after the COVID-19 infection; 402 participated in the baseline phase and completed an in depth cognitive, clinical and laboratory assessment about one month later. More than one third of the screened subjects presented a CI (COG+); it was associated to age, education, male gender, COVID-19 severity, and presence of anosmia, dyspnea at rest and exertional dyspnea during the acute phase. COG+ subjects showed a higher severity of depression, anxiety and post-traumatic distress, and worse global functioning, than subjects without CI. The MCCB showed that 45% of the subjects had a CI involving attention, working memory, verbal learning, visual learning, and reasoning and problem solving. Finally, neurocognitive functioning was inversely correlated with LDH blood levels, a potential biomarker of disease severity. According to our findings, cognitive functioning should be routinely and periodically assessed in COVID-19 patients, especially in older subjects, who experienced more severe COVID-19 symptoms. In case of persisting dysfunctions cognitive training programs should be considered as treatment strategies.
TNF alpha  antagonist compounds and methods of using the same are disclosed. The compounds comprise a molecular surface that is substantially similar to at least one molecular surface of human TNF alpha . The compounds bind to TNF receptors but do not produce the same biological effect as that which occurs when TNF alpha  binds to a TNF receptor. Methods of inhibiting tumor necrosis factor activity are disclosed. The methods comprise the step of contacting tumor necrosis factor alpha with a TNF alpha  antagonist. Methods of treating individuals suspected of suffering from or being susceptible to a disease or disorder mediated by tumor necrosis factor-alpha activity are disclosed. The methods comprise the step of administering to said individual a therapeutically effective amount of a TNF alpha  antagonist.
<P>PROBLEM TO BE SOLVED: To provide a safe anti-inflammatory agent and painkiller derived from a natural product and having little side effect.  <P>SOLUTION: The anti-inflammatory agent and painkiller contain at least one of kaempferol 3-O-rhamnoside and quercitrin as an active ingredient. These compounds can be obtained by extracting a defatted seed of kiwi with hydrated ethanol. Therefor, the extract of the seed of the kiwi can be the active ingredient, which is preferable. The anti-inflammatory agent and the painkiller using the compounds as the active ingredients can be contained in a food, a medicine and an external preparation for the skin.  <P>COPYRIGHT: (C)2007,JPO&INPIT