anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
A process for the production of extremely pure galanthamine and galanthamine derivatives is provided. Racemic bromine narwedine is debrominated under palladium catalysis. The reaction mixture is then worked-up in the presence of oxygen or peroxides so that the palladium catalyst is converted into an insoluble form that can be easily separated. Further reaction is carried out by reduction of enantiomerically pure narwedine to form enantiomerically pure galanthamine, which is then alkylated or dealkylated, so that a corresponding substitution on the ring-nitrogen atom is achieved. By further purification, such as recrystallization, residual portions of palladium of below 5 ppm are achieved. The pure galanthamine can then be directly used as a pharmaceutical raw material.
BACKGROUND AND OBJECTIVE: Advanced liver fibrosis is a critical stage in the evaluation of chronic liver disease (CLD), holding clinical significance in the development of treatment strategies and estimating the disease progression.
METHODS: This paper proposes an innovative Global-Local Cross-View Network (GLCV-Net) for the automatic diagnosis of advanced liver fibrosis from ultrasound (US) B-mode images. The proposed method consists of three main components: 1. A Segmentation-enhanced Global Hybrid Feature Extractor for segmenting the liver parenchyma and extracting global features; 2. A Heatmap-weighted Local Feature Extractor for selecting candidate regions and automatically identifying suspicious areas to construct local features; 3. A Scale-adaptive Fusion Module to balance the contributions of global and local scales in evaluating advanced liver fibrosis.
RESULTS: The predictive performance of the model was validated on an internal dataset of 1003 chronic liver disease (CLD) patients and an external dataset of 46 CLD patients, both subjected to liver fibrosis staging through pathological assessment. On the internal dataset, GLCV-Net achieved 86.9% accuracy, 85.0% recall, 85.4% precision, and 85.2% F1-score. Further validation on the external dataset confirmed its robustness, with scores of 86.1% in accuracy, 83.1% in recall, 80.8% in precision, and 81.9% in F1-score.
CONCLUSION: These results underscore the GLCV-Net's potential as a promising approach for non-invasively and accurately diagnosing advanced liver fibrosis in CLD patients, breaking through the limitations of traditional methods by integrating global and local information of liver fibrosis, significantly enhancing diagnostic accuracy.
Ocular solutions containing at least one macrolide antibiotic and/or mycophenolic acid provide anti-inflammatory, anti-cell proliferation, anti-cell migration, anti-angiogenesis, antimicrobial, and antifungal effects. In one embodiment, the solution is administered intraocularly after cataract surgery before insertion of a replacement intraocular lens, resulting in reduced posterior capsular opacification which may eliminate the need for a subsequent surgery. The solution may be one that is invasively administered, for example, an irrigation or volume replacement solution containing at least one macrolide antibiotic such as tacrolimus, sirolimus, everolimus, cyclosporine, and ascomycin, or mycophenolic acid. The solution may be one that is non-invasively or topically administered in the form of drops, ointments, gels, creams, etc. and may include eye lubricants and contact lens solutions. The solution may contain a supratherapeutic concentration of agent(s) so that a therapeutic concentration of a topically administered solution accumulates in a diseased ocular structure sufficient to treat the disease. The agent(s) may be formulated with polymers or other components for extended or slow release to provide a substantially constant concentration over the course of treatment.
PROBLEM TO BE SOLVED: To easily produce a glucide containing trehalose having a refined and good sweetness, properties for regulating an osmotic pressure, a formativeness, moisture retention, properties for preventing precipitation of other glucide, etc., in high yield by allowing a maltose-trehalose converting enzyme to act on a solution containing sucrose. SOLUTION: This glucide containing trehalose is obtained by allowing a maltose-trehalose converting enzyme to act on a solution containing sucrose. An enzyme produced by a microorganism such as Pseudomonas putida H262 (FERM BP-4579) is preferably used as the before maltose-trehalose converting enzyme. The objective glucide containing trehalose is obtained by allowing the maltose-trehalose converting enzyme, preferably >=10 unit enzyme per gram solid, to act on the solution containing sucrose. The content of the trehalose is preferably increased by allowing an invertase to act on the liquid obtained by the enzymatic reaction and further treating the resultant liquid with a column chromatography by using a salt-type strong acid cation exchange resin.  Moreover, the reaction under the maltose-trehalose converting enzyme is preferably performed at 0-70 deg.C and within the pH range of 6-8.5.
BACKGROUND: In the era of targeted therapies, the influence of aging on cancer management varies from one patient to another. Assessing individual frailty using geriatric tools has its limitations, and is not appropriate for all patients especially the youngest one. Thus, assessing the complementary value of a potential biomarker of individual aging is a promising field of investigation. The chronic myeloid leukemia model allows us to address this question with obvious advantages: longest experience in the use of tyrosine kinase inhibitors, standardization of therapeutic management and response with minimal residual disease and no effect on age-related diseases. Therefore, the aim of the BIO-TIMER study is to assess the biological age of chronic myeloid leukemia or non-malignant cells in patients treated with tyrosine kinase inhibitors and to determine its relevance, in association or not with individual frailty to optimize the personalised management of each patient.
METHODS: The BIO-TIMER study is a multi-center, prospective, longitudinal study aiming to evaluate the value of combining biological age determination by DNA methylation profile with individual frailty assessment to personalize the management of chronic myeloid leukemia patients treated with tyrosine kinase inhibitors. Blood samples will be collected at diagnosis, 3 months and 12 months after treatment initiation. Individual frailty and quality of life will be assess at diagnosis, 6 months after treatment initiation, and then annually for 3 years. Tolerance to tyrosine kinase inhibitors will also be assessed during the 3-year follow-up. The study plans to recruit 321 patients and recruitment started in November 2023.
DISCUSSION: The assessment of individual frailty should make it possible to personalize the treatment and care of patients. The BIO-TIMER study will provide new data on the role of aging in the management of chronic myeloid leukemia patients treated with tyrosine kinase inhibitors, which could influence clinical decision-making.
TRIAL REGISTRATION: ClinicalTrials.gov , ID NCT06130787; registered on November 14, 2023.
Patients undergo collection of blood samples after starting immunotherapy and then at 6 and 12 months. Patients also undergo DXA scan over 5-10 minutes after starting immunotherapy and at 12 months.
Obesity has been associated with the occurrence and prevalence of various chronic metabolic diseases. The management of obesity has evolved to focus not only on reducing weight, but also on preventing obesity-related complications. Studies have shown that bioactive components in natural products like white kidney bean extract (WKBE), propolis ethanolic extract (PEE), and chromium picolinate (CrPi3) showed anti-obesity properties. However, no studies have examined the outcomes of combining any of these nutraceutical supplements. We compared the effects of HFD supplemented with WKBE, WKBE+PEE, or WKBE+PEE+CrPi3 against control and obese groups using Sprague-Dawley rats fed a 45% high-fat diet as an in vivo model. Nutritional parameters, biochemical parameters, and biomarkers of cardiovascular disease, liver function, kidney function, and gut health were among the comparable effects. Our findings showed that combining the three nutraceutical supplements had a synergetic effect on reducing weight gain, food utilization rate, abdominal fat, serum lipids, arterial and hepatic lipids, risk of cardiovascular disease, and blood glucose level, in addition to improving renal function and gut microbiota. We attributed these effects to the α-amylase inhibitor action of WKBE, flavonoids, and polyphenol content of PEE, which were potentiated with CrPi3 resulting in a further reduction or normalization of certain parameters.
INTRODUCTION: Balance and gait impairments are common in people with hereditary spastic paraplegia (HSP) and often result in falls. Measures that identify patients at risk of falling are clinically relevant, but relatively unexplored in HSP. Here, we evaluated the potential of different balance and gait constructs to (1) identify differences between healthy controls and people with HSP and (2) discriminate between fallers and non-fallers with HSP.
METHODS: We included 33 people with pure-HSP and 15 healthy controls. We assessed balance confidence (six-item Activities-specific Balance Confidence scale), clinical balance capacity (Mini-Balance Evaluation Systems Test) and gait capacity (ten-meter Walk Test). Biomechanical measures included spatiotemporal gait variability, mediolateral Margin of Stability (MoS), Foot Placement Deviation (FPD), and Local Divergence Exponents (LDEs) of trunk and pelvis, derived from treadmill-walking at comfortable and fixed gait speeds. People with HSP logged their falls during a fifteen-week period and were categorized as 'faller' (≥1 fall) or 'non-faller'.
RESULTS: People with HSP had significantly lower balance confidence, balance capacity, and gait capacity compared to age-matched controls. People with HSP also showed reduced gait stability, reflected by increased spatiotemporal gait variability, FPD, and LDEs of trunk and pelvis. Overall, 44 % of people with HSP were categorized as 'faller'. Balance confidence (AUC:0.84) and balance capacity (AUC:0.75) discriminated fallers from non-fallers, whereas none of the biomechanical measures significantly differed.
CONCLUSION: Balance confidence, clinical balance and gait capacity, and biomechanical measures are affected in HSP, but clinical measures showed potential to differentiate fallers from non-fallers in people with HSP.
After peripheral nerve injury (PNI), the long-term healing process at the injury site involves a progressive accumulation of collagen fibers and the development of localized scar tissue. Excessive formation of scar tissue within nerves hinders the process of nerve repair. In this study, we demonstrate that scar formation following nerve injury induces alterations in the local physical microenvironment, specifically an increase in nerve stiffness. Recent research has indicated heightened expression of Piezo1 in Schwann cells (SCs). Our findings also indicate Piezo1 expression in SCs and its association with suppressed proliferation and migration. Transcriptomic data suggests that activation of Piezo1 results in elevated expression of senescence-associated genes. GO enrichment analysis reveals upregulation of the TGF-β pathway. Overall, our study highlights the potential for Piezo1-induced signaling to regulate SC senescence and its potential significance in the pathophysiology of fibrotic scar formation surrounding peripheral nerves.
In Study 109, the efficacy and safety of switching from ATRIPLA, TRUVADA plus atazanavir (given with either cobicistat or ritonavir), or STRIBILD to GENVOYA once daily were evaluated in a randomized, open-label trial of virologically-suppressed (HIV-1 RNA less than 50 copies per mL) HIV-1 infected adults (N=1436). Subjects must have been suppressed (HIV-1 RNA less than 50 copies per mL) on their baseline regimen for at least 6 months and had no known resistance-associated substitutions to any of the components of GENVOYA prior to study entry. Subjects were randomized in a 2:1 ratio to either switch to GENVOYA at baseline (N=959), or stay on their baseline antiretroviral regimen (N=477). Subjects had a mean age of 41 years (range 21–77), 89% were male, 67% were White, and 19% were Black. The mean baseline CD4+ cell count was 697 cells per mm3 (range 79–1951).

Subjects were stratified by prior treatment regimen. At screening, 42% of subjects were receiving TRUVADA plus atazanavir (given with either cobicistat or ritonavir), 32% were receiving STRIBILD, and 26% were receiving ATRIPLA.

Treatment outcomes of Study 109 through 96 weeks are presented in Table 17.

Treatment outcomes were similar across subgroups receiving ATRIPLA, TRUVADA plus atazanavir (given with either cobicistat or ritonavir), or STRIBILD prior to randomization. In Study 109, the mean increase from baseline in CD4+ cell count at Week 96 was 60 cells per mm3 in GENVOYA-treated subjects and 42 cells per mm3 in subjects who stayed on their baseline regimen.
OBJECTIVES: Reduced cardiac outflow due to left ventricular hypertrophy has been suggested as a potential risk factor for development of cerebral white matter disease. Our study aimed to examine the correlation between left ventricular geometry and white matter disease volume to establish a clearer understanding of their relationship, as it is currently not well-established.
METHODS: Consecutive patients from 2016 to 2021 who were ≥18 years and underwent echocardiography, cardiac MRI, and brain MRI within one year were included. Four categories of left ventricular geometry were defined based on left ventricular mass index and relative wall thickness on echocardiography. White matter disease volume was quantified using an automated algorithm applied to axial T2 FLAIR images and compared across left ventricular geometry categories.
RESULTS: We identified 112 patients of which 34.8 % had normal left ventricular geometry, 20.5 % had eccentric hypertrophy, 21.4 % had concentric remodeling, and 23.2 % had concentric hypertrophy. White matter disease volume was highest in patients with concentric hypertrophy and concentric remodeling, compared to eccentric hypertrophy and normal morphology with a trend-P value of 0.028. Patients with higher relative wall thickness had higher white matter disease volume (10.73 ± 10.29 cc vs 5.89 ± 6.46 cc, P = 0.003), compared to those with normal relative wall thickness.
CONCLUSION: Our results showed that abnormal left ventricular geometry is associated with higher white matter disease burden, particularly among those with abnormal relative wall thickness. Future studies are needed to explore causative relationships and potential therapeutic options that may mediate the adverse left ventricular remodeling and its effect in slowing white matter disease progression.
The invention discloses an application of a combination drug in preparing a drug for treating nasopharyngeal carcinoma, wherein the combination drug comprises NLG-919 and cisplatin, and the concentration ratio of NLG-919 to cisplatin is 5-7: 1, NLG-919 has a concentration of 12.5-560. Mu. Mol/L and cisplatin has a concentration of 2.5-80. Mu. Mol/L. The invention also discloses application of the combination drug in restoring the sensitivity of nasopharyngeal carcinoma cisplatin resistant cells to cisplatin, wherein the combination drug comprises NLG-919 and cisplatin, and the concentration ratio of NLG-919 to cisplatin is 1-7: 1, NLG-919 has a concentration of 2.5-560. Mu. Mol/L and cisplatin has a concentration of 2.5-80. Mu. Mol/L. NLG-919 remarkably enhances the induction capability of cisplatin on apoptosis of nasopharyngeal carcinoma cells; meanwhile, the inhibition of cisplatin on the migration of nasopharyngeal carcinoma cells is enhanced, and the tumor metastasis is effectively overcome.
Recombinant TNF and recombinant IFN-G have been shown to be effective against the virus which causes AIDS and ARC in some laboratory studies, but may increase virus replication in other laboratory studies. Previous studies in humans showed no increase in virus cultures and some decrease in measurements of virus. Extensive preclinical data show that TNF and IFN-G are more effective together than separately in laboratory and animal studies. As single agents, both TNF and IFN-G have modest effect against HIV. Studies have demonstrated that TNF and IFN-G, in combination, can not only inhibit HIV infection of previously uninfected cells, but also can selectively induce the destruction of acutely infected target cells.

Patients with ARC who are positive for HIV antibody are randomized to receive one of three treatment arms: (1) TNF alone by intramuscular injection (IM); (2) IFN-G alone by IM; (3) TNF plus IFN-G. Patients receive IM injections 3 times weekly for 4 months (16 weeks). Repeated physical examinations and laboratory tests are used to monitor patients' safety. Serial HIV cultures and core antigen assays are employed to obtain evidence of antiviral activity and serial T cell and skin tests are used to measure immunologic effect.
BACKGROUND: Primaquine is an 8-aminoquinoline antimalarial. It is the only widely available treatment to prevent relapses of Plasmodium vivax malaria. The 8-aminoquinolines cause dose-dependent haemolysis in glucose-6-phosphate dehydrogenase deficiency (G6PDd). G6PDd is common in malaria endemic areas but testing is often not available. As a consequence primaquine is underused.
METHODS: We conducted an adaptive pharmacometric study to characterise the relationship between primaquine dose and haemolysis in G6PDd. The aim was to explore shorter and safer primaquine radical cure regimens compared to the currently recommended 8-weekly regimen (0.75 mg/kg once weekly), potentially obviating the need for G6PD testing. Hemizygous G6PDd healthy adult Thai and Burmese male volunteers were admitted to the Hospital for Tropical Diseases in Bangkok. In Part 1, volunteers were given ascending dose primaquine regimens whereby daily doses were increased from 7.5 mg up to 45 mg over 15-20 days. In Part 2 conducted at least 6 months later, a single primaquine 45 mg dose was given.
RESULTS: 24 volunteers were enrolled in Part 1, and 16 in Part 2 (13 participated in both studies). In three volunteers, the ascending dose regimen was stopped because of haemolysis (n=1) and asymptomatic increases in transaminases (n=2; one was hepatitis E positive). Otherwise the ascending regimens were well tolerated with no drug-related serious adverse events. In Part 1, the median haemoglobin concentration decline was 3.7 g/dL (range: 2.1-5.9; relative decline of 26% [range: 15-40%]). Primaquine doses up to 0.87 mg/kg/day were tolerated subsequently without clinically significant further falls in haemoglobin. In Part 2, the median haemoglobin concentration decline was 1.7 g/dL (range 0.9-4.1; relative fall of 12% [range: 7-30% decrease]). The ascending dose primaquine regimens gave seven times more drug but resulted in only double the haemoglobin decline.
CONCLUSIONS: In patients with Southeast Asian G6PDd variants, full radical cure treatment can be given in under 3 weeks compared with the current 8-week regimen.
FUNDING: Medical Research Council of the United Kingdom (MR/R015252/1) and Wellcome (093956/Z/10/C, 223253/Z/21/Z).
CLINICAL TRIAL NUMBER: Thai Clinical Trial Registry: TCTR20170830002 and TCTR20220317004.
With the development of video-assisted thoracoscopic surgery (VATS) techniques, minimally invasive thoracic surgery has evolved considerably over the last three decades. The concept of "tubeless" involves non-intubated anesthesia with spontaneous ventilation and no chest tube placement. Chest tube placement always causes pain, and its duration is known to be one of the most important factors influencing hospital stay and costs. Early tube removal allows patients to breathe deeply with less pain, which leads to more compliance with chest physiotherapy, as demonstrated by a concomitant improvement in patients' ventilatory function. Hence, more and more experienced surgeons choose the omission of chest tube placement after lung wedge resection. However, based on previous retrospective studies, residual pneumothorax was noted in about 10% cases, and some of them need re-intervention. Hence, the investigators designed a intra-operative two-lumen catheterization as improved drainage strategy. Therefore, this study evaluates the viability and safety of two-lumen catheterization versus omission of chest tube placement in patients with lung wedge resection.
(Also see CONTRAINDICATIONS, WARNINGS, CLINICAL PHARMACOLOGY: Drug Interactions) 

Nelfinavir is an inhibitor of CYP3A. Coadministration of VIRACEPT and drugs primarily metabolized by CYP3A (e.g., dihydropyridine calcium channel blockers, HMG-CoA reductase inhibitors, immunosuppressants and PDE5 inhibitors) may result in increased plasma concentrations of the other drug that could increase or prolong both its therapeutic and adverse effects. (See Tables 10 and 11). Nelfinavir is metabolized by CYP3A and CYP2C19. Coadministration of VIRACEPT and drugs that induce CYP3A or CYP2C19, such as rifampin, may decrease nelfinavir plasma concentrations and reduce its therapeutic effect. Coadministration of VIRACEPT and drugs that inhibit CYP3A or CYP2C19 may increase nelfinavir plasma concentrations.

Drug interaction studies reveal no clinically significant drug interactions between nelfinavir and didanosine, lamivudine, stavudine, zidovudine, efavirenz, nevirapine, or ketoconazole and no dose adjustments are needed. In the case of didanosine, it is recommended that didanosine be administered on an empty stomach; therefore, nelfinavir should be administered with food one hour after or more than 2 hours before didanosine.

Based on known metabolic profiles, clinically significant drug interactions are not expected between VIRACEPT and dapsone, trimethoprim/sulfamethoxazole, or itraconazole.
Pregnancy Category C. Studies in pregnant rats showed that abacavir is transferred to the fetus through the placenta. Fetal malformations (increased incidences of fetal anasarca and skeletal malformations) and developmental toxicity (depressed fetal body weight and reduced crown-rump length) were observed in rats at a dose which produced 35 times the human exposure, based on AUC. Embryonic and fetal toxicities (increased resorptions, decreased fetal body weights) and toxicities to the offspring (increased incidence of stillbirth and lower body weights) occurred at half of the above-mentioned dose in separate fertility studies conducted in rats. In the rabbit, no developmental toxicity and no increases in fetal malformations occurred at doses that produced 8.5 times the human exposure at the recommended dose based on AUC.

There are no adequate and well-controlled studies in pregnant women. ZIAGEN should be used during pregnancy only if the potential benefits outweigh the risk.

Antiretroviral Pregnancy Registry: To monitor maternal-fetal outcomes of pregnant women exposed to ZIAGEN, an Antiretroviral Pregnancy Registry has been established. Physicians are encouraged to register patients by calling 1-800-258-4263.
A nozzle, an apparatus, and a method are provided for mass production of dual-layer microparticles used as microcarriers. The nozzle includes a nozzle body having a first fluid passageway and a cover mounted to the nozzle body and having a second fluid passageway. A plurality of extension tubes is communicated with an end of the first fluid passageway and is spaced from each other. Each extension tube includes an outlet port distant to the first fluid passageway. A plurality of sleeves is communicated with the second fluid passageway. Each sleeve includes an opening distant to the second fluid passageway. Each extension tube extends into one of the sleeves. An outer wall of each extension tube is spaced from an inner wall of one of the sleeves. The outlet port of each extension tube is located between the second fluid passageway and the opening of one of the sleeves.