anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
The exact mechanism of action of methoxsalen is not known. The best-known biochemical reaction of methoxsalen is with DNA. Methoxsalen, upon photoactivation, conjugates and forms covalent bonds with DNA which leads to the formation of both monofunctional (addition to a single strand of DNA) and bifunctional adducts (crosslinking of psoralen to both strands of DNA). Reactions with proteins have also been described. The formation of photoadducts results in inhibition of DNA synthesis, cell division and epidermal turnover.

For the palliative treatment of Cutaneous T-Cell Lymphoma, Photopheresis consists of removing a portion of the patient's blood and separating the red blood cells from the white cell layer (buffy coat) by centrifugation. The red cells are returned to the patient and the UVADEX® Sterile Solution is then injected into the instrument and mixed with the buffy coat. The instrument then irradiates this drug-cell mixture with ultraviolet light (UVA light, 320–400 nm) and returns the treated cells to the patient. See the appropriate Operator's Manual for details of this process. Although extracorporeal phototherapy exposes less than 10% of the total body burden of malignant cells to methoxsalen plus light, some patients achieve a complete response. Animal studies suggest that the photopheresis may activate an immune-mediated response against the malignant T-cells.

Use of the THERAKOS® UVAR and UVAR XTS® Photopheresis Systems after oral administration of methoxsalen were previously approved for the treatment of Cutaneous T-Cell Lymphoma. Interpatient variability in peak plasma concentration after an oral dose of methoxsalen ranges from 6 to 15 fold. UVADEX® is injected directly into the separated buffy coat in the instrument in an attempt to diminish this interpatient variability and to improve the exposure of the cells to the drug.

Methoxsalen is reversibly bound to serum albumin and is also preferentially taken up by epidermal cells. Methoxsalen is rapidly metabolized in humans, with approximately 95% of the drug excreted as metabolites in the urine within 24 hours.

Systemic administration of methoxsalen followed by UVA exposure leads to cell injury. The most obvious manifestation of this injury after skin exposure is delayed erythema, which may not begin for several hours and peaks at 48–72 hours. The inflammation is followed over several days to weeks, by repair which is manifested by increased melanization of the epidermis and thickening of the stratum corneum.

The total dose of methoxsalen delivered in UVADEX® is substantially lower (approximately 200 times) than that used with oral administration. More than 80% of blood samples collected 30 minutes after reinfusion of the photoactivated buffy coat had methoxsalen levels below detection limits of the assay (<10 ng/ml), and the mean plasma methoxsalen concentration was approximately 25 ng/ml.
Apply product to the affected area(s) twice daily or as directed by a physician. Product should not be used in excess of recommendations or for prolonged use in the anal canal. If the condition does not respond to repeated courses of product or should worsen, discontinue use and seek the advice of your physician.

Patient Directions for Rectal Administration: Remove moist wipe from box, tear open the package, gently clean the affected area and discard moist wipe. (Note: The moist wipe does not contain any of the prescribed active ingredients.) The cap and foil seal should be removed from the tube and the applicator tip firmly screwed onto the end of the tube and tightened. (Do not over tighten.) While holding the tube, gently squeeze the tube until a small amount of gel comes out of the applicator openings. This will lubricate the applicator tip. Gently insert the applicator tip into anal area. Continue squeezing the body of the tube as you move it around the areas of discomfort, and lastly, around and in the anal opening (if directed by physician). Do not completely insert the applicator and tube into the anus or insert deep into the rectum. Do not insert a loose applicator tip into the anus or rectum. Once application is completed, the tube and applicator tip should be gently removed and discarded.
The present invention provides an improved process for preparing modafinil, whereby it may be isolated in high purity by a single crystallization. The process produces modafinil free of sulphone products of over-oxidation and other byproducts. The invention further provides new crystalline Forms II-VI of modafinil and processes for preparing them. Each of the new forms is differentiated by a unique powder X-ray diffraction pattern. The invention further provides pharmaceutical compositions containing novel modafinil Forms II-IV and VI. ® KIPO & WIPO 2007
This intervention will adapt an already-existing evidence-based Centering Parenting program. Investigators will not provide clinical care to participants. Investigators will also address topics that are specific to African American families. Investigators will conduct 9 90 min sessions via zoom and in person.
Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disease characterized by recurrent attacks of fever and polyserositis. Its first description as a new entity was published by Siegal in 1945. Colchicine has been the treatment of choice for this disease since 1972. Significant progress has been made over the years in understanding FMF's clinical features, diagnosis, mode of inheritance, pathogenesis and therapeutic approach. However, many old paradigms related to FMF have proven inaccurate, leading to the emergence of new concepts that provide more precise insights. The term 'FMF' is no longer appropriate as the disease is found beyond the Mediterranean basin. The concept of diagnosis based only upon clinical ground proved to be wrong. The paradigm that MEFV mutations in FMF lead to loss of function of the encoded peptide pyrin turned out to be a gain of function mutation. Finally, the concept that as a genetic disease FMF should be treated for life was found to be inaccurate for the subpopulation of the heterozygote patients. Thus, the breakthroughs of identifying the gene associated with the disease (MEFV) and the deciphering of its pathogenesis revolutionized our old paradigms and replaced them with new and more precise insights.
INTRODUCTION AND HYPOTHESIS: Genitourinary fistula is a devastating ailment that has an impact on women's physical health, mental health, emotional health, and financial security. The management of genitourinary fistula depends on the type, size, and duration of fistula formation. The purpose of this study is to report the features of genitourinary fistula in Iranian women and our experience in the management of fistula.
METHODS: Retrospective chart reviews of 283 patients were performed to determine the cause of the fistula, prior repairs, tissue interposition, and the success rate. The operation was considered successful if the patient did not have any urine leakage during the observation time.
RESULTS: The mean (SD) age of women was 49.51 (19.39; range: 21-70) years, Of these, 137 (52.9%) had a history of previous genitourinary fistula surgery. The average fistula was 1.53 (0.041) cm in size. The median (interquartile range) operation lasted 70 (15) min. The success rate after fistula repair was 91.5%. The typical follow-up period lasted 13.26 (range: 1-88) months. Forty-three (15.2%) patients had a big fistula (>2.5 cm) and 4 patients (1.4%) had a history of pelvic radiation therapy, among other reasons for failure. After a second repair, all patients' initial failures were resolved. There were no significant complications, as classified by Clavien-Dindo class 2 or greater. Additionally, there were no bowel, ureteral, or nerve injuries.
CONCLUSIONS: Our patients with genitourinary fistula had a successful outcome following repair techniques, without any significant morbidity or mortality.
Oral bacteria naturally secrete extracellular vesicles (EVs), which have attracted attention for their promising biomedical applications including cancer therapeutics. However, our understanding of EV impact on tumor progression is hampered by limited in vivo models. In this study, we propose a facile in vivo platform for assessing the effect of EVs isolated from different bacterial strains on oral cancer growth and dissemination using the larval zebrafish model. EVs were isolated from: wild-type Aggregatibacter actinomycetemcomitans and its mutant strains lacking the cytolethal distending toxin (CDT) or lipopolysaccharide (LPS) O-antigen; and wild-type Porphyromonas gingivalis. Cancer cells pretreated with EVs were xenotransplanted into zebrafish larvae, wherein tumor growth and metastasis were screened. We further assessed the preferential sites for the metastatic foci development. Interestingly, EVs from the CDT-lacking A. actinomycetemcomitans resulted in an increased tumor growth, whereas EVs lacking the lipopolysaccharide O-antigen reduced the metastasis rate. P. gingivalis-derived EVs showed no significant effects. Cancer cells pretreated with EVs from the mutant A. actinomycetemcomitans strains tended to metastasize less often to the head and tail compared to the controls. In sum, the proposed approach provided cost- and labor-effective yet efficient model for studying bacterial EVs in oral carcinogenesis, which can be easily extended for other cancer types. Furthermore, our results support the notion that these nanosized particles may represent promising targets in cancer therapeutics.
The disclosure relates to a conjugate comprising a membrane anchoring agent, polyethylene glycol effective and a functional molecule that is in increasing the lifespan of sperm in the female reproductive tract, wherein the functional molecule is attached to the polyethylene glycol by an attachment group. Example conjugates are shown in the abstract figure. The functional molecule may be catalase, glutathione, CD55, CD59, CD73, DNaseI or SPAM1. The membrane anchoring agent may be a lipid, such as cholesterol, diacylglycerolipids, dialkylglycerolipids, glycerophospholipids, sphingosine derived diacyl- and dialkyl- lipids, ceramide, phosphatidate, phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl serine, phosphatidyl inositol or phosphatidyl glycerol. The attachment group may be ester amine reactive groups, maleimide, vinyl sulfone, iodoacetamide, orthopyridyl disulphide, hydrazide, benzotriazole, succinimidyl carbonate or succinimidyl active esters based on priopionic and butanoic acids. The disclosure also relates to a method for preparing a composition for use in artificial insemination or in vitro fertilization using sperm and the conjugate.
Placebo delivered in capsule format. Participants will be instructed to take 2 capsules of placebo for 4 weeks during the run-in period. On day 1 participants will be instructed to take 2 capsules of placebo in the morning before breakfast for 12 weeks.
Serious or life-threatening hypoventilation may occur at any time during the use of fentanyl transdermal system especially during the initial 24–72 hours following initiation of therapy and following increases in dose.

Because significant amounts of fentanyl continue to be absorbed from the skin for 20‑27 hours or more after the patch is removed, hypoventilation may persist beyond the removal of fentanyl transdermal system. Consequently, patients with hypoventilation should be carefully observed for degree of sedation and their respiratory rate monitored until respiration has stabilized.

The use of concomitant CNS active drugs requires special patient care and observation.

Respiratory depression is the chief hazard of opioid agonists, including fentanyl the active ingredient in fentanyl transdermal system. Respiratory depression is more likely to occur in elderly or debilitated patients, usually following large initial doses in non-tolerant patients, or when opioids are given in conjunction with other drugs that depress respiration.

Respiratory depression from opioids is manifested by a reduced urge to breathe and a decreased rate of respiration, often associated with the "sighing" pattern of breathing (deep breaths separated by abnormally long pauses). Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. This makes overdoses involving drugs with sedative properties and opioids especially dangerous.

Fentanyl transdermal system should be used with extreme caution in patients with significant chronic obstructive pulmonary disease or cor pulmonale, and in patients having a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression. In such patients, even usual therapeutic doses of fentanyl transdermal system may decrease respiratory drive to the point of apnea. In these patients, alternative non-opioid analgesics should be considered, and opioids should be employed only under careful medical supervision at the lowest effective dose.
A man in his 60s presented to an outside hospital with persistent groin pain and a scrotal mass which was thought to be a recurrent hernia. Three months after initial presentation, the patient was found to have dedifferentiated liposarcoma (LPS) of the spermatic cord. LPS of the spermatic cord is a rare entity; however, clinicians should have LPS on the differential diagnosis especially in men with recurrent scrotal pain and mass. If unrecognised, LPS is associated with a high degree of morbidity and mortality. LPS can be subdivided into well-differentiated LPS, dedifferentiated LPS, myxoid LPS and pleomorphic LPS. In patients with advanced or metastatic LPS, chemotherapy consisting of Adriamycin, ifosfamide and mesna is used despite LPS being relatively chemoresistant. Therapies inhibiting mouse double minute 2 homologue, an oncoprotein that is a negative regulator of the tumour suppressor p53, appear to be promising in preclinical trials.
Administration of captopril results in a reduction of peripheral arterial resistance in hypertensive patients with either no change, or an increase, in cardiac output. There is an increase in renal blood flow following administration of captopril and glomerular filtration rate is usually unchanged. In patients with heart failure, significantly decreased peripheral (systemic vascular) resistance and blood pressure (afterload), reduced pulmonary capillary wedge pressure (preload) and pulmonary vascular resistance, increased cardiac output, and increased exercise tolerance time (ETT) have been demonstrated.

Reductions of blood pressure are usually maximal 60 to 90 minutes after oral administration of an individual dose of captopril. The duration of effect is dose related and is extended in the presence of a thiazide-type diuretic. The full effect of a given dose may not be attained for 6 to 8 weeks (see DOSAGE AND ADMINISTRATION). The blood pressure lowering effects of captopril and thiazide-type diuretics are additive. In contrast, captopril and beta-blockers have a less than additive effect.

Blood pressure is lowered to about the same extent in both standing and supine positions. Orthostatic effects and tachycardia are infrequent but may occur in volume-depleted patients. Abrupt withdrawal of captopril has not been associated with a rapid increase in blood pressure.  
  
Studies in rats and cats indicate that captopril does not cross the blood-brain barrier to any significant extent.  
  
Hydrochlorothiazide: Thiazides affect the renal tubular mechanism of electrolyte reabsorption. At maximal therapeutic dosage all thiazides are approximately equal in their diuretic potency.  
Thiazides increase excretion of sodium and chloride in approximately equivalent amounts. Natriuresis causes a secondary loss of potassium and bicarbonate.  
The mechanism of the antihypertensive effect of thiazides is unknown. Thiazides do not affect normal blood pressure.  
The mean plasma half-life of hydrochlorothiazide in fasted individuals has been reported to be approximately 2.5 hours.  
Onset of diuresis occurs in two hours and the peak effect at about four hours. Its action persists for approximately six to twelve hours. Hydrochlorothiazide is eliminated rapidly by the kidney.
Then the investigators will conduct the field testing (Beta test) with patient and clinician facing the decision in real time. The purpose of Beta test is to test the usability of DA_LCMT 2.0 in "real-world setting". Clinician and patients will use the DA_LCMT 2.0 for real-time decision making. The conversation of decision progress will be audio-recorded. After the decision is made by patients, structured interview will be conducted and audio-recorded separately between clinician and patients. All the field testing interviews will conducted one-on-one and written informed consent will be obtained prior to each interview. Each field testing interview will last for about 20 minutes.
The invention discloses a skin care product and a preparation method thereof. The core component of the product is a reducing agent and a precipitator, wherein the reducing agent is selected from vitamin C, vitamin E, glutathione, vitamin A and vitamin D, and the precipitator is selected from calcium carbonate, pearl powder, magnesium carbonate, barium carbonate, calcium phosphate, magnesium phosphate, barium phosphate, calcium silicate, magnesium silicate and barium silicate. The molar ratio of the reducing agent and the precipitator is 1:(3-6). The core component in the skin care product accounts for 5-10wt%. PH value of the skin care product is 6.6-7.4. The skin care product can be used for safely and effectively removing iron which accelerates natural aging and optical aging of skins in the skins, and can be mixed in use with conventional skin care products to realize a better anti-aging effect.
Students spend a considerable amount of time in school. This study aimed to determine the prevalence of musculoskeletal pain and the association between the pain and suitability of school furniture and daily activities among primary school and university students. A total of 238 primary and university students participated in the study. The adapted Nordic questionnaire was used to assess pain prevalence, the BackPEI questionnaire was used to assess school-related factors, and student furniture mismatch calculations were performed to determine the anthropometric suitability of school furniture. Most students did not have a proper body posture while sitting, did not lift objects properly, and used TV and computer frequently. A high student-furniture mismatch was found for seat and desk height. The neck, lower back, shoulders, and upper back were the most affected body parts. Our study confirmed that musculoskeletal pain occurs in primary school students and increases with age, especially lower back pain. Proper backpack wearing was found to be an important factor in alleviating neck pain. Students who sat or lifted objects properly were more likely to report upper back pain, and students whose backrest height was appropriate were more likely to report lower back pain. Further efforts should be made to establish a comparable study protocol using objective methods to obtain more valid and reliable data to study school-related risk factors for musculoskeletal pain in students using prospective study protocols.
The SIT consisted of a combination of aerobic, resistance, balance, and flexibility exercises. Exercise started with 5 min of warm-up followed by bouts of 5-10 min of exercise consisting of 5-20 s all-out sprints followed by 15-45 s of low cadence recovery (1:3-1:2 work-rest ratio). The duration of the sprints and active recovery were modified throughout the program. To ensure that participants exercised at the appropriate intensity, the OMNI scale 8-10 (Stanish \& Aucoin, 2007) was applied during the home intervention, and an HR chest band (H10 Polar, Electro, Kempele, Finland) was used during the gym intervention.
This study aims to compare outcomes of rib fracture patients with and without COVID-19 in Michigan. Data from the Michigan Trauma Quality Improvement Program (MTQIP) identified adults hospitalized from January 1, 2020, to October 31, 2022, with at least one rib fracture and a completed COVID-19 test on admission. Patients were propensity score matched 1:1 using 20 variables. The primary outcome was hospital length of stay (LOS). Secondary outcomes were mortality, ventilator days, intensive care unit (ICU) LOS, pneumonia, and ventilator-assisted pneumonia (VAP). 13,305 total patients were identified. 232 patients matched into both the COVID+ and COVID- groups. COVID was associated with increased LOS (7 days vs. 5 days, P < 0.001). There were no significant differences between the two groups when evaluating secondary outcomes. Our study indicates that although COVID-19 infection is associated with increased LOS, COVID may not contribute to additional morbidity or mortality in traumatic rib fracture patients.
Staphylococcus aureus is a pulmonary pathogen associated with substantial human morbidity and mortality. As vaccines targeting virulence determinants have failed to be protective in humans, other factors are likely involved in pathogenesis. Here we analysed transcriptomic responses of human clinical isolates of S. aureus from initial and chronic infections. We observed upregulated collagenase and proline transporter gene expression in chronic infection isolates. Metabolomics of bronchiolar lavage fluid and fibroblast infection, growth assays and analysis of bacterial mutant strains showed that airway fibroblasts produce collagen during S. aureus infection. Host-adapted bacteria upregulate collagenase, which degrades collagen and releases proline. S. aureus then imports proline, which fuels oxidative metabolism via the tricarboxylic acid cycle. Proline metabolism provides host-adapted S. aureus with a metabolic benefit enabling out-competition of non-adapted strains. These data suggest that clinical settings characterized by airway repair processes and fibrosis provide a milieu that promotes S. aureus adaptation and supports infection.