anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Keratoconus is a progressive eye disorder primarily affecting individuals in adolescence and early adulthood. The ectatic changes in the cornea cause thinning and cone-like steepening leading to irregular astigmatism and reduced vision. Keratoconus is a complex disorder with a multifaceted aetiology and pathogenesis, including genetic, environmental, biomechanical and cellular factors. Environmental factors, such as eye rubbing, UV light exposure and contact lens wearing, are associated with disease progression. On the cellular level, a complex interplay of hormonal changes, alterations in enzymatic activity that modify extracellular membrane stiffness, and changes in biochemical and biomechanical signalling pathways disrupt collagen cross-linking within the stroma, contributing to structural integrity loss and distortion of normal corneal anatomy. Clinically, keratoconus is diagnosed through clinical examination and corneal imaging. Advanced imaging platforms have improved the detection of keratoconus, facilitating early diagnosis and monitoring of disease progression. Treatment strategies for keratoconus are tailored to disease severity and progression. In early stages, vision correction with glasses or soft contact lenses may suffice. As the condition advances, rigid gas-permeable contact lenses or scleral lenses are prescribed. Corneal cross-linking has emerged as a pivotal treatment aimed at halting the progression of corneal ectasia. In patients with keratoconus with scarring or contact lens intolerance, surgical interventions are performed.
FIELD: organic chemistry, chemical technology, biochemistry, medicine. SUBSTANCE: invention proposes three alternative methods for preparing derivatives of pyrazolo[3,4-d] pyrimidine-7-one of the general formula (I)   or their pharmaceutically acceptable salts wherein: Q represents oxygen atom; R 1  represents hydrogen atom, lower alkyl, azetidinyl, -(C 1 -C 6 -alkyl)-Het wherein Het is taken among pyridyl, morpholinyl and piperidinyl, or (C 1 -C 6 -alkyl)-phenyl being azethidinyl, Het or phenyl in two latter groups can be substituted optionally with cyano-group, lower alkyl, CO 2 R 7 ; R 2  represents lower alkyl; R 3  represents lower alkyl or cycloalkyl; R 4  represents halogen atom, nitro-group, C(O)R 8 ; R 7  and R 8  represent lower alkyl. The first method involves interaction of compound of the formula (II)   wherein X represents removing group; R 1 , R 2 , R 4  represent as they are given above with  - OR 3  generated from alcohol R 3 OH in the presence of a base or from solution of alcohol salt ZOR 3  in suitable solvent wherein R 3  means as given above; Z means cation of alkaline or alkaline-earth metal in the presence of trapping agent of the formula: TOC(O)W wherein OT represents OR 3  or OT represents residue of volume alcohol or non-nucleophilic alcohol or residue of alcohol that can be removed by azeotropy method during reaction; C(O)W means residue of carboxylic acid. The second method involves interaction of compound of the formula (III)   wherein X represents removing group; R 1 , R 2 , R 4  mean such as they are given above with  - OR 3  generated as described above in the presence of above characterized trapping agent. The third method involves interaction of compound of the formula (V)   wherein Q and R 1 -R 4  have values given in the cl. 1 in the presence of a base taken among the group consisting of steric hindered base alkoxide, amide, hydride, oxide, carbonate or hydrocarbonate of alkaline or alkaline- earth metal and trapping agent characterized above. Invention provides preparing compounds of the formula (I) that are inhibitors of cyclic guanosine- -3',5'-monophosphate phosphodiesterase and useful, for example, in treatment of erectile dysfunction in males. EFFECT: improved preparing method, valuable medicinal properties of compounds, high yield. 7 cl, 3 tbl, 11 ex
In both conditions, the contents of the UP manual were worked following the 2nd edition of the UP manual (Barlow et al., 2018). In the 5-session version, modules 1 (Motivation for change and commitment to treatment) and 8 (Achievement, maintenance, and relapse prevention) were removed and modules 6 and 7 (interoceptive and emotional exposure) were combined. The sessions were group sessions, 2 hours long and weekly.
This is a phase II single arm study with sequential treatments available by response where all participants begin therapy with a combination of celecoxib and interferon alpha-2b (CI, treatment-1). Response to CI therapy will be assessed at six months by clinical and radiographic evaluations. Those patients who have achieved a partial response (improvement in pain, improvement in functioning, or ≥50% reduction in tumor size) or complete response (resolution of pain, and normalization of functioning with a ≥ 90% reduction in tumor size) will continue with the same CI therapy for up-to two years on study.
BACKGROUND: A multidrug-resistant lineage of Staphylococcus epidermidis named ST215 is a common cause of prosthetic joint infections and other deep surgical site infections in Northern Europe, but is not present elsewhere. The increasing resistance among S. epidermidis strains is a global concern. We used whole-genome sequencing to characterize ST215 from healthcare settings.
RESULTS: We completed the genome of a ST215 isolate from a Swedish hospital using short and long reads, resulting in a circular 2,676,787 bp chromosome and a 2,326 bp plasmid. The new ST215 genome was placed in phylogenetic context using 1,361 finished public S. epidermidis reference genomes. We generated 10 additional short-read ST215 genomes and 11 short-read genomes of ST2, which is another common multidrug-resistant lineage at the same hospital. We studied recombination's role in the evolution of ST2 and ST215, and found multiple recombination events averaging 30-50 kb. By comparing the results of antimicrobial susceptibility testing for 31 antimicrobial drugs with the genome content encoding antimicrobial resistance in the ST215 and ST2 isolates, we found highly similar resistance traits between the isolates, with 22 resistance genes being shared between all the ST215 and ST2 genomes. The ST215 genome contained 29 genes that were historically identified as virulence genes of S. epidermidis ST2. We established that in the nucleotide sequence stretches identified as recombination events, virulence genes were overrepresented in ST215, while antibiotic resistance genes were overrepresented in ST2.
CONCLUSIONS: This study features the extensive antibiotic resistance and virulence gene content in ST215 genomes. ST215 and ST2 lineages have similarly evolved, acquiring resistance and virulence through genomic recombination. The results highlight the threat of new multidrug-resistant S. epidermidis lineages emerging in healthcare settings.
Organizing pneumonia (OP) is defined histologically by the presence of granulation tissue within alveolar ducts and alveoli. Recently, several lymphoid neoplasms have been implicated as a risk factor for OP, however, OP as a primary manifestation of malignancy transformation has not been widely reported in the literature. Here, we report a case of a patient with a history of chronic lymphocytic leukemia (CLL) who presented with weight loss, low-grade fever, lymphadenopathy, and bilateral pulmonary infiltrates revealed in imaging studies. Video-assisted thoracoscopic lung biopsy showed CLL cells within the pulmonary vessels and areas of OP in the lung parenchyma. Subsequent lymph nodes biopsies were consistent with CLL transformation to diffuse large B-cell lymphoma (DLBCL). To our knowledge, this is the first reported case of OP associated with CLL transformation into DLBCL. This case suggests that OP could represent a form of immunological reaction to ongoing Richter transformation.
The Hepatitis C virus (HCV) uses host cellular lipid metabolism to produce infectious virus particles. In order to find cellular factors involved in the multiplication of HCV, the present inventors used HCV-cc-infected cells to screen for the siRNA library targeting host genes that regulate lipid metabolism and lipid droplet formation. Of 10 final candidate genes, the gene encoding AAM-B was selected and characterized. siRNA-mediated AAM-B knockdown was shown to impair production of infectious HCV particles in both Jc1 RNA electroplated cells and Jc1-infected cells. AAM-B knockdown exerts no effect on lipid droplet formation. Also, AAM-B was found to interact with NS4B through the C-terminal region of NS4B. It was confirmed using transient or stable AAM-B expression that AAM-B colocalized with NS4B in the cytoplasm. Immunofluorescence data shows that AAM-B recruits NS4B to sites in close proximity of lipid droplets to facilitate HCV propagation. Collectively, the data shows that HCV utilizes AAM-B through NS4B to facilitate viral propagation.
The invention is a kind of Chinese traditional medicine preparation for curing hemorrhoids and the manufacturnig method. It selects a little part of mirabilis jalapa root and crushes them into middle powder. The effective materials in the residue mirabilis jalapa root, rhubarb, goldthread are produced ito tiny powder by water or alcohol extraction. The tiny powder and the middle powder are blended evenly, and they are produced into preparation by current technology. Compared with current technology, the invention has a good effect, low cost no toxic side effect, convenient for use. It has functions of clearing away heat and desiccation, hemostasis. It applies to internal hemorrhoid bleeding and external hemorrhoid swelling and pain.
BACKGROUND: The association between upper gastrointestinal symptoms and delayed gastric emptying (GE) shows conflicting results. This study aimed to assess whether the symptoms of the Gastroparesis Cardinal Symptom Index (GCSI) and/or the scores were associated with the result of GE tests and whether they could predict delayed GE.
METHODS: Patients referred for suspected gastroparesis (GP) were included in a prospective database. Demographical data, medical history, and symptoms of the GCSI score were collected for each patient. A GE scintigraphy was then performed with a 4-hour recording. Delayed GE was defined as a retention rate ≥ 10% at 4 h.
RESULTS: Among 243 patients included in this study, 110 patients (45%) had delayed GE. The mean age (49.9 vs. 41.3 years; p < 0.001) and weight loss (9.4 kg vs. 5.6 kg; p = 0.025) were significantly higher in patients with delayed GE. Patients with diabetes or a history of surgery had a higher prevalence of delayed GE (60% and 78%, respectively) than patients without comorbidity (17%; p < 0.001). The GCSI score was higher in patients with delayed GE (3.06 vs. 2.80; p = 0.045), but no threshold was clinically relevant to discriminate between patients with normal and delayed GE. Only vomiting severity was significantly higher in patients with delayed GE (2.19 vs. 1.57; p = 0.01).
CONCLUSION: GE testing should be considered when there are symptoms such as a higher weight loss, comorbidities (diabetes, and history of surgery associated with GP), and the presence of vomiting. Other symptoms and the GCSI score are not useful in predicting delayed GE.
PURPOSE: To provide an article capable of generating aerosol without generating any combustion product by inserting a specific noncombustion type heat source into a volatile component contg. a flavoring material and a drug. CONSTITUTION: In this article, a heat-resistant, electrically insulating cartridge 20 that has an open end 22 in the vicinity of an air intake region 25 and a tightly sealed end 28 in the vicinity of the side of a mouthpiece end 30 of a rod 15, is inserted into the rod 15 consisting of a base material 11 on which a volatile component contg. a flavoring material and a drug is supported and which is wrapped with a cylindrical outer-wrap 13. Also, a noncombustion type heat source 35 consisting of at least two metallic materials each of which is composed of a mixture contg. Fe and Mg in a ratio of Fe:Mg of 10:1 to 1:1 and capable of electrochemically acting on the other, and a dispersant that is solid in the ordinary state, such as cellulose, is inserted into this cartridge 20 and encapsulated in it with a moisture-impermeable plug 38.  Then, this rod 15 and a filter element 43 consisting of a filter medium 45 encircled with an outer-wrap 47 are joined together by using mouthpiece paper 50.
OBJECTIVE: This study aims to characterize patient-reported chemotherapy-induced toxicity in patients with breast cancer, determine its association with treatment regimens and patient characteristics, identify toxicity symptom clusters within a specific chemotherapy timeframe and analyze the correlation between symptom clusters within and between the timeframe to understand the changes and influences across chemotherapy.
METHODS: Forty-six patient-reported toxicities during neoadjuvant/adjuvant chemotherapy for breast cancer were evaluated using adapted CTCAE version 4.0. Chi-Square/Fisher's Exact test was performed to analyze the difference in the incidence of toxicity symptoms by chemotherapy regimens. Poisson regression performed to assess factors associated with patient's total chemotherapy toxicity. Exploratory factor analysis (EFA) conducted to identify symptom clusters at T1 (first half) and T2 (second half of planned cycle). Factor scores were generated and Spearman correlation performed to explore the factor scores correlation between symptom clusters.
RESULTS: A total of 142 patients with stage I-III breast cancer were included. The incidence of several toxicities differed significantly among three chemotherapy regimens. Subjects age ≥51 years are associated with lower number of reported toxicity (IRR/incidence rate ratio = 0.94, 95% confidence interval/CI 0.88 to 0.99, p = 0.042). Receiving more chemotherapy cycles are associated with higher number of reported toxicity (IRR = 1.06, 95% CI 1.03 to 1.10, p<0.001). Two symptom clusters identified at T1 (psychoneurological-pain/PNP-T1 and gastrointestinal-psychological/GIP-T1 cluster) and three at T2 (psychoneurological-pain/PNP-T2, epithelial/EPI-T2, and gastrointestinal cluster/GI-T2), with moderate-strong positive correlation between PNP-T1 and GIP-T2 (p<0.001), PNP-T1 and PNP-T2 (p<0.001), and GIP-T1 and PNP-T2 (p<0.001).
CONCLUSIONS: This study investigated 46 patient-reported toxicities prospectively during adjuvant/neoadjuvant chemotherapy for early breast cancer. Anthracycline-taxane combination regimen had higher proportions of toxicity incidence. Subject's age and number of chemotherapy cycles significantly associated with total number of toxicity symptoms. Two symptom clusters at T1 and three at T2 were identified, with significant correlation between symptom clusters within and between chemotherapy timeframe.
UNLABELLED: A number of neurotransmitters have been detected in tumor microenvironment and proved to modulate cancer oncogenesis and progression. We previously found that biosynthesis and secretion of neurotransmitter 5-hydroxytryptamine (5-HT) was elevated in colorectal cancer cells. In this study, we discovered that the HTR2B receptor of 5-HT was highly expressed in colorectal cancer tumor tissues, which was further identified as a strong risk factor for colorectal cancer prognostic outcomes. Both pharmacological blocking and genetic knocking down HTR2B impaired migration of colorectal cancer cell, as well as the epithelial-mesenchymal transition (EMT) process. Mechanistically, HTR2B signaling induced ribosomal protein S6 kinase B1 (S6K1) activation via the Akt/mTOR pathway, which triggered cAMP-responsive element-binding protein 1 (CREB1) phosphorylation (Ser 133) and translocation into the nucleus, then the phosphorylated CREB1 acts as an activator for ZEB1 transcription after binding to CREB1 half-site (GTCA) at ZEB1 promoter. As a key regulator of EMT, ZEB1, therefore, enhances migration and EMT process in colorectal cancer cells. We also found that HTR2B-specific antagonist (RS127445) treatment significantly ameliorated metastasis and reversed EMT process in both HCT116 cell tail-vein-injected pulmonary metastasis and CT26 cell intrasplenic-injected hepatic metastasis mouse models.
IMPLICATIONS: These findings uncover a novel regulatory role of HTR2B signaling on colorectal cancer metastasis, which provide experimental evidences for potential HTR2B-targeted anti-colorectal cancer metastasis therapy.
The data presented below include references to the steady-state acyclovir AUC observed in humans treated with 1 gram valacyclovir hydrochloride given orally 3 times a day to treat herpes zoster. Plasma drug concentrations in animal studies are expressed as multiples of human exposure to acyclovir [see Clinical Pharmacology (12.3)].  
Valacyclovir was noncarcinogenic in lifetime carcinogenicity bioassays at single daily doses (gavage)of valacyclovir giving plasma acyclovir concentrations equivalent to human levels in the mouse bioassay and 1.4 to 2.3 times human levels in the rat bioassay. There was no significant difference in the incidence of tumors between treated and control animals, nor did valacyclovir shorten the latency of tumors.  
Valacyclovir was tested in 5 genetic toxicity assays. An Ames assay was negative in the absence or presence of metabolic activation. Also negative were an in vitro cytogenetic study with human lymphocytes and a rat cytogenetic study.  
In the mouse lymphoma assay, valacyclovir was not mutagenic in the absence of metabolic activation. In the presence of metabolic activation (76% to 88% conversion to acyclovir), valacyclovir was mutagenic.  
Valacyclovir was mutagenic in a mouse micronucleus assay.  
Valacyclovir did not impair fertility or reproduction in rats at 6 times human plasma levels.
EPRONTIA can cause fetal harm when administered to a pregnant woman. Data from pregnancy registries indicate that infants exposed to topiramate in uterohave an increased risk of major congenital malformations, including but not limited to cleft lip and/or cleft palate (oral clefts), and of being small for gestational age (SGA). When multiple species of pregnant animals received topiramate at clinically relevant doses, structural malformations, including craniofacial defects, and reduced fetal weights occurred in offspring [ see Use in Specific Populations (8.1) ]. 

Consider the benefits and the risks of EPRONTIA when administering this drug in women of childbearing potential, particularly when EPRONTIA is considered for a condition not usually associated with permanent injury or death [ see Use in Specific Populations ( 8.1), Patient Counseling Information ( 17) ]. EPRONTIA should be used during pregnancy only if the potential benefit outweighs the potential risk. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus [ see Use in Specific Populations ( 8.1) ].
BACKGROUND: Very low birthweight infants (VLBWIs) often undergo chest radiographic examinations without standardization or objectivity. This study aimed to assess the association of two radiographic scores, the Brixia and radiographic assessment of lung edema (RALE), with oxygenation index (OI) in ventilated VLBWIs and to determine the optimal cutoff values to predict hypoxic respiratory severity.
METHODS: VLBWIs who received invasive respiratory support with arterial lines between January 2010 and October 2023 were enrolled in this study (n = 144). The correlation between the Brixia or RALE scores and OI was investigated. Receiver operating characteristic curve analysis was performed to determine the optimal cutoff points of the two radiographic scores for predicting OI values (OI ≥5, ≥10, and ≥15).
RESULTS: The enrolled infants had a median gestational age of 27 weeks (interquartile range [IQR], 25-28 weeks) and a median birthweight of 855 g (IQR, 684-1003 g). Radiographic scoring methods correlated with the OI (Brixia score: r = 0.79, p < 0.001; RALE score: r = 0.72, p < 0.001). The optimal cutoff points for predicting OI values were as follows: Brixia score: OI ≥5, 10; OI ≥10, 13; OI ≥15, 15; RALE score: OI ≥5, 22; OI ≥10, 31; and OI ≥15, 40.
CONCLUSIONS: Brixia and RALE scores are useful predictive markers of the oxygenation status in intubated VLBWIs with stable hemodynamics. These scores are easy to use and promising tools for clinicians to identify patients with a higher risk of hypoxic respiratory failure.
The placebo will have identical appearance and taste with the study product only lacking the bacteria. All subjects from this group will receive 2 x 20 mg omeprazole per day and Placebo 1 chewable tablet per day for 28 days.
INTRODUCTION: Aortic stenosis (AS) is common affecting >13% of adults over the age of 75 years. In people who develop symptoms, without valve replacement, prognosis is dismal with mortality as high as 50% at 1 year. In asymptomatic patients, the timing of valve intervention is less well defined and a strategy of watchful waiting is recommended. Many, however, may develop symptoms and attribute this to age related decline, rather than worsening AS. Timely intervention in asymptomatic severe AS is critical, since delayed intervention often results in poor outcomes. Proactive surveillance of symptoms, quality of life and functional capacity should enable timely identification of people who will benefit from aortic valve replacement. There are no data however, to support the clinical and cost effectiveness of such an approach in a healthcare setting in the UK. The aim of this pilot trial is to test the feasibility of a full-scale randomised controlled trial (RCT) to determine the utility of proactive surveillance in people with asymptomatic severe AS to guide the timing of intervention.
METHODS AND ANALYSIS: APRAISE-AS is a multi-centre, non-blinded, two-arm, parallel group randomised controlled trial of up to 66 participants aged >18 years with asymptomatic severe AS. Participants will be randomised to either standard care or standard care supplemented with the APRAISE-AS intervention. Primary outcomes will capture; adherence to and participant acceptability of the intervention, recruitment and retention rates, and completeness of data collection. The findings will be used to inform the sample size and most appropriate outcome measure(s) for a full-scale RCT and health economic evaluation.
ETHICS AND DISSEMINATION: Ethical approval was granted by the Black Country REC, reference: 22/WM/0214. Results will be submitted for publication in peer-reviewed journals and disseminated at local, regional and national meetings where appropriate.
TRIAL REGISTRATION NUMBER: ISRCTN19413194 registered on 14.07.2023.
1. E-2-[4-(4-chloro-1,2-diphenyl-but-1-enyl)phenoxy]ethanol or a pharmaceutically acceptable ester thereof. 2. A pharmaceutical composition which comprises E-2-[4-(4-chloro-1,2-diphenyl-but-1-enyl)phenoxy]ethanol or a pharmaceutically acceptable ester thereof as an active ingredient together with a pharmaceutically acceptable carrier. 3. A method of lowering serum cholesterol levels which method comprises administering to a patient in need of such treatment an effective amount of E-2-[4-(4-chloro-1,2-diphenyl-but-1-enyl)phenoxy]ethanol or a pharmaceutically acceptable ester thereof. 4. A method for the prevention or treatment of atherosclerosis which method comprises administering to a patient in need of such treatment an effective amount of E-2-[4-(4-chloro-1,2-diphenyl-but-1-enyl)phenoxy]-ethanol or a pharmaceutically acceptable ester thereof. 5. A method of hormone replacement therapy (HRT) which method comprises administering to a patient in need of such therapy an effective amount of E-2-[4-(4-chloro-1,2-diphenyl-but-1-enyl)phenoxy]ethanol or a pharmaceutically acceptable ester thereof.