anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
OBJECTIVES: I. Determine the maximum tolerated dose or hematopoietically active dose of leridistim administered with induction chemotherapy in older patients with acute myeloid leukemia. II. Determine the effect of leridistim on the duration of grade IV neutropenia during the induction course in these patients. III. Determine the safety and tolerability of leridistim in these patients. IV. Compare the effect of leridistim vs filgrastim (G-CSF) on the duration of thrombocytopenia, the incidence of infection, and the need for IV antibiotics in these patients. V. Compare the effect of leridistim vs G-CSF on the number of days of platelet and/or red blood cell transfusions in these patients.

OUTLINE: This is a dose escalation study of leridistim and then a randomized, open label, multicenter study. Patients are randomized to one of two treatment arms. All patients receive induction chemotherapy consisting of daunorubicin IV over 15-30 minutes on days 1-3 and cytarabine IV continuously on days 1-7. Patients who do not achieve aplasia after one induction course may receive a second course. Dose Escalation Phase: Patients receive leridistim subcutaneously (SQ) every other day beginning on day 11-14 and continuing for 42 days or until blood counts recover. Cohorts of 6 patients receive escalating doses of leridistim until the maximum tolerated dose (MTD) or hematopoietically active dose (HAD) has been determined. The MTD is defined as the dose prior to the dose level at which at least 2 of the same dose limiting toxicities occur in different patients. Consolidation Phase: Patients then receive consolidation chemotherapy consisting of cytarabine IV over 1 hour every 12 hours (patients 70 years and under) or every 24 hours (patients over 70 years) on days 1-6. Beginning 24-48 hours after completion of consolidation chemotherapy, patients receive leridistim as above. Randomized Phase: Eligible patients will receive induction and consolidation chemotherapy as outlined above. Then patients are randomized to one of two treatments. Arm I: Patients receive leridistim SQ every other day for up to 42 days or until blood counts recover. Arm II: Patients receive filgrastim (G-CSF) SQ daily for up to 42 days or until blood counts recover. Patients are followed at day 30 and then at 6 and 12 months.

PROJECTED ACCRUAL: A total of 86 patients (36 for phase I and 50 for phase II) will be accrued for this study.
Alzheimer's disease (AD) is distinguished by cognitive dysfunction and neuroinflammation in the brain. 2'-Fucosyllactose (2'-FL) is a major human milk oligosaccharide (HMO) that is abundantly present in breast milk and has been demonstrated to exhibit immunomodulatory effects. However, the role of 2'-FL and HMO in gut microbiota modulation in relation to AD remains insufficiently investigated. This study aimed to elucidate the preventive effect of the 2'-FL and HMO impact of AD and the relevant mechanism involved. Here, the behavioral results showed that 2'-FL and HMO intervention decreased the expression of Tau phosphorylation and amyloid-β (Aβ), inhibited neuroinflammation, and restored cognitive impairment in AD mice. The metagenomic analysis proved that 2'-FL and HMO intervention restored the dysbiosis of the gut microbiota in AD. Notably, 2'-FL and HMO intervention significantly enhanced the relative abundance of Clostridium and Akkermansia. The metabolomics results showed that 2'-FL and HMO enhanced the oleoyl-l-carnitine metabolism as potential drivers. More importantly, the levels of oleoyl-l-carnitine were positively correlated with the abundances of Clostridium and Akkermansia. These results indicated that 2'-FL and HMO had therapeutic potential to prevent AD-induced cognitive impairment, which is of great significance for the treatment of AD.
The Continuous Enrollment is a Facebook-delivered weight loss intervention. For this group, the study team continued to enroll participants through week 8. This arm captures only those participants that were added to the group during these 8 weeks. They were enrolled in the study after the original 80 participants were randomized.
Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer and it lacks specific therapeutic targets and effective treatment protocols. By analyzing a proteomic TNBC dataset, we found significant upregulation of sideroflexin 1 (SFXN1) in tumor tissues. However, the precise function of SFXN1 in TNBC remains unclear. Immunoblotting was performed to determine SFXN1 expression levels. Label-free quantitative proteomics and liquid chromatography-tandem mass spectrometry were used to identify the downstream targets of SFXN1. Mechanistic studies of SFXN1 and cellular inhibitor of PP2A (CIP2A) were performed using immunoblotting, immunofluorescence staining, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Functional experiments were used to investigate the role of SFXN1 in TNBC cells. SFXN1 was significantly overexpressed in TNBC tumor tissues and was associated with unfavorable outcomes in patients with TNBC. Functional experiments demonstrated that SFXN1 promoted TNBC growth and metastasis in vitro and in vivo. Mechanistic studies revealed that SFXN1 promoted TNBC progression by inhibiting the autophagy receptor TOLLIP (toll interacting protein)-mediated autophagic degradation of CIP2A. The pro-tumorigenic effect of SFXN1 overexpression was partially prevented by lapatinib-mediated inhibition of the CIP2A/PP2A/p-AKT pathway. These findings may provide a new targeted therapy for patients with TNBC.
This is a pilot study to describe the immunological responses and clinical outcome associated with administration of recombinant human Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) as surgical adjuvant therapy in patients with malignant melanoma who are at high risk for recurrence (Stage II T4, III and IV). The immunological responses include serum neopterin levels. In a sub-set of study participants, additional immunologic testing will be done, including monocyte cytotoxicity to a melanoma cell line and phenotypic and functional markers of dendritic and T cell activation in peripheral blood mononuclear cells. The clinical end points of the study include safety, time to disease recurrence, time to disseminated disease, and survival. Eligible patients are those with high-risk melanoma who are clinically tumor free following surgery. Treatment will consist of GM-CSF at 125 g/m2 once daily (maximum dose 250 g) for 14 days followed by 14 days of rest (28 day cycle) for 1 year. Clinical status will be monitored until death or until the patient has been tumor free for five years, whichever event occurs first. Immunologic responses will be determined pretreatment, at the end of the first 14 days of dosing (Day 15), after the 14-day rest period (Day 29) and at the end of 14 days of dosing in cycles 6 (Day 155) and 13 (Day 351). Clinical outcome will be determined according to patient risk group (ultra-high risk Stage IIIC or IV versus high-risk Stage II T4, Stage IIIA and Stage IIIB). The pilot study will also assess the association of the immunological responses with clinical response and safety by patient risk group.
Participants in the Once Weekly Structured Contact group will take part in an 6-month exercise intervention and attend one structured group exercise session per week. They will engage in aerobic and resistance training for approximately 80 minutes per exercise session. Additionally, they will attend three exercise evaluations and six study visits.
The dosages of the D-IVA-GSE and I-IVA-GSE are based on the FITT principle of exercise prescription (frequency, intensity, time, and type). The D-IVA-GSE group will perform two, 15- minute GSE sessions (30-minutes total per day), seven days per week.
The optimal goal of neoadjuvant chemotherapy (NAC) for breast cancer is to achieve pathologic complete response (pCR) with the least toxicity. As more effective therapies become available, one challenge is how to evaluate the response of tumor in a timely manner, so an optimal regimen can be given to the patient. Reliable imaging methods that can monitor and predict NAC response are needed. MRI is known as the most accurate imaging modality to evaluate the response to NAC based on tumor shrinkage, but so far there is no reliable parameter that can be measured at early times after the administration of drugs to predict the final treatment outcome. Furthermore, some patients may have contradiction to receive MRI, or cannot tolerate the long scan time in a prone position. Other imaging modalities that can measure early functional (particularly metabolic) changes are being investigated, and have shown some success. In this study investigators will assess the role of an MR-compatible scinti-mammography (MRI-SMM) system for monitoring and predicting NAC response. A total of 75 breast cancer patients receiving NAC will be enrolled, and each subject will receive 3 imaging studies before, during, and after completing NAC. The aims are: 1) to compare the tumor size measured by SMM and MRI at different times; 2) to evaluate the respective diagnostic accuracy of the post-NAC residual disease measured by SMM and MRI by comparing to pathological examination results as the gold standard; 3) to investigate the respective and combined ability of MRI and SMM, based on pre-treatment and early changes in the first follow-up imaging, for predicting pathologic complete response (pCR). The diagnostic results obtained using MRI and SMM from tumors of varying stages at different times during NAC will provide important information for establishing the role of a standalone SMM system, as well as the combined MRI-SMM system, for management of breast cancer patients.
For the treatment of status epilepticus in children, the solution should be injected slowly, taking one minute for administration (See WARNINGS, particularly for use in children). For other indications, the solution should be injected slowly taking at least one minute for each 5 mg (1 mL) given. Do not use small veins, such as those on the dorsum of the hand or wrist. Extreme care should be taken to avoid intra-arterial administration or extravasation.

Do not mix or dilute diazepam with other solutions or drugs in syringe or infusion container. If it is not feasible to administer diazepam directly intravenous, it may be injected slowly through the infusion tubing as close as possible to the vein insertion.

Once the acute symptomatology has been properly controlled with diazepam injection, the patient may be placed on oral therapy with diazepam if further treatment is required.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

NOTE: Solution may appear colorless to light yellow.
This pilot study will collect information about the the potential to use an evidence-based skills training program designed for older people with serious mental illness (SMI), the Helping Older People Experience Success (HOPES) program, to help nursing home residents with SMI gain the skills needed to successfully live in the community. Although HOPES was originally designed to help older people with SMI maintain their residence in the community, the curriculum holds promise for helping nursing home residents with SMI to learn how to return to life in the community. Positive findings would be used to develop a grant application for a larger study of HOPES in nursing home residents with SMI. To evaluate the feasibility and acceptability of HOPES in nursing home settings, the investigators will enroll up to 12 residents of the Glencliff Home in Glencliff, New Hampshire. Participants will be individuals interested in discharge from Glencliff and are willing to attend multiple weekly skills training classes and several assessment sessions. Study participation will last until 6 months after discharge from Glencliff.
OBJECTIVE: Increasing perceptual load alters behavioral outcomes in post-stroke fatigue (PSF). While the effect of perceptual load on top-down attentional processing is known, here we investigate if increasing perceptual load modulates bottom-up attentional processing in a fatigue dependent manner.
METHODS: In this cross-sectional observational study, in 29 first-time stroke survivors with no clinical depression, an auditory oddball task consisting of target, standard, and novel tones was performed in conditions of low and high perceptual load. Electroencephalography was used to measure auditory evoked potentials. Perceived effort was rated using the visual analog scale at regular intervals during the experiment. Fatigue was measured using the fatigue severity scale. The effect of fatigue and perceptual load on behavior (response time, accuracy, and effort rating) and auditory evoked potentials (amplitude and latency) was examined using mixed model ananlysis of variances (ANOVA).
RESULTS: Response time was prolonged with greater perceptual load and fatigue. There was no effect of load or fatigue on accuracy. Greater effort was reported with higher perceptual load both in high and low fatigue. p300a amplitude of auditory evoked potentials (AEP) for novel stimuli was attenuated in high fatigue with increasing load when compared to low fatigue. Latency of p300a was longer in low fatigue with increasing load when compared to high fatigue. There were no effects on p300b components, with smaller N100 in high load conditions.
INTERPRETATION: High fatigue specific modulation of p300a component of AEP with increasing load is indicative of distractor driven alteration in orienting response, suggestive of compromise in bottom-up selective attention in PSF.
OBJECTIVE: There is a high prevalence and incidence rate of asymptomatic sexually transmitted infections (STIs) during pregnancy in adolescent girls and young women in Africa. The association between STIs and pregnancy outcomes in a hyperepidemic HIV setting has not been well described.
METHODS: Pregnant women, HIV-1 negative and <28 weeks' gestation at three primary health clinics in KwaZulu-Natal, South Africa were enrolled from February 2017 to March 2018. Vaginal swabs collected at the first and later antenatal visits were stored and retrospectively tested for HSV-2, Trichomonas vaginalis, Chlamydia trachomatis and Neisseria gonorrhoeae at the end of the study. The association between STIs detected at first and later antenatal visits and pregnancy outcome was assessed using multivariable logistic regression models adjusted for maternal age and treatment received for symptomatic STIs.
RESULTS: Testing positive Mycoplasma genitalium at the first antenatal visit was significantly associated with low birth weight (odds ratio [OR] 5.22; 95% confidence interval [CI]: 1.10-15.98). Testing positive for T. vaginalis at the repeat visit was significantly associated with preterm births (OR 2.37; 95% CI: 1.11-5.03), low birth weight (OR 2.56; 1.16-5.63) and a composite adverse pregnancy outcome (OR 2.11; 95% CI: 1.09-4.08). Testing positive for HSV-2 at the repeat visit was also likely associated with experiencing a preterm birth or any adverse pregnancy outcome (OR 3.39; 95% CI: 0.86-13.3) (P = 0.096).
CONCLUSIONS: Among predominantly asymptomatic STIs, M. genitalium detected at baseline visit was significantly associated with low birth weight, while T. vaginalis detected at the repeat visit in later pregnancy was significantly associated with preterm birth. Further research is warranted to study the impact of etiological testing of STIs at more than one antenatal visit and empirical treatment on pregnancy outcomes.
New systems, devices, methods and other techniques for eliciting, standardizing and recording patient-reported data in clinical healthcare settings are provided. A new form of specialized computer hardware and software control system is provided, applying new machine learning techniques for translating patients' freeform verbalizations and other patient-reported data to standardized significance codes. In some embodiments, the system also translates such significance codes into standardized medical terminology that is more easily actionable by healthcare providers, as part of a new form of personal health record generated by patients (“PHRP”). In some embodiments, health-related data is normalized based on techniques known as translation vectors. Such translation vectors generate standardized significance codes based on common usage of terms by user(s) of the control system (e.g., a cohort of demographically-related patient users), and subsequent entries of such terms by such a user then causes the control system to enter data at least partially defined by the same significance codes.In some embodiments, patients' personal health records, including language usage and experiences over time, also adjust the translation of such freeform verbalizations into significance codes, and medically-actionable terminology. For example, in some embodiments, such records impact the designation of probable diagnoses, triggers, comorbidities and suggested treatments, as then recorded and suggested to healthcare providers. In some such embodiments, new graphical user interfaces are provided for generating, storing and managing such a PHRP, and generating interventions based thereon.In some embodiments, the system generates a colloquy, e.g., a script, to aid a healthcare provider in efficiently eliciting significant patient-reported data in a standard format. In some embodiments, such a script is modified and generated in real time, based on the course of the colloquy.In some embodiments, techniques involving external, objectively sensed healthcare measurements are implemented, which the system may use to validate and calibrate translation vectors between subjective expressions from patients to universal significance codes, based on related expressions from other, similar patients (e.g., from a similar demographic cohort of patients).
A compound represented by the general formula (I), a salt of the compound, or a hydrate of either thereof. They have an excellent antipruritic effect and have an excellent metabolic effect. The compound represented by the general formula (I), salt of the compound, or hydrate of either thereof, in a preparation for external use, has excellent absorbability into the skin. The preparation for external use has excellent stability because the ingredients incorporated are less apt to separate out even in long-term storage. (I) [In the formula, R represents hydroxy, C1-6 alkoxy optionally substitutedby C1-6 alkoxy, or amino optionally substituted by C1-6 alkyl.].
Regulatory elements responsible for tissue-specific transcriptional regulation of the human β3-adrenergic receptor (β3-AR) are identified. A region localized between -6.50 and -6.30 kb of the proximal promoter contained three sequences that act synergistically to achieve full transcriptional activity. One segment, termed segment A, contains an Sp1 binding site. Another of the sequences, termed segment B, is a binding site for a trans-acting factor present in cells that constitutively express β3-AR. In a specific embodiment, the trans-acting factor is expressed in neuroblastoma (SK-N-MC) and brown adipose tissue cells, but little or not at all in CV-1, HeLa, or white adipose tissue cells. The third segment, C, is an S1 nuclease-sensitive site having CCTT repeats. Recombinant vectors under control of this transcriptional regulation region, particularly containign the B and C segments, provide a substrate for high throughput assays, such as reporter gene assays, to identify compounds that can increase the level of expression of β3-AR. The B segment nucleic acids also provide for isolation and cloning of the trans-acting factor. Mechanisms of transcriptional regulation and identification of other adjacent proteins involved in the regulation of the hβ3-AR gene expression are provided.
The intervention is a in-class yoga course taught by yoga instructors for 3 times per week for 3 months. This class is based on "Peggy Cappy's Program: More Yoga for Every Body". Class is taught at Sanford Wellness Centers in Sioux Falls, South Dakota and Fargo, North Dakota. Each class in 1 hour in length.
Participants complete questionnaires about quality of life and preferences for supportive care treatment, wear accelerometerundergo heart rate variability(HRV) testing over 10-15 minutes while both lying down and standing, complete a walking test, wear an accelerometer for a period of 1 week, and undergo a single Dual X-ray Absorptiometry (iDXA) scan over 10 minutes. Other interventions include: Laboratory Biomarker Analysis, Quality-of-Life Assessments, and othe Questionnaire Administration.
Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, and arises from melanocytes within the choroid plexus of the eye. The development of metastasis is common and occurs in approximately 50% of patients with posterior UM within 15 years of initial diagnosis and treatment. As no effective systemic therapy has yet been identified for this disease, outcomes for metastatic UM are poor with a median survival of 12 months.

There is no FDA approved therapy for patients with advanced UM. Studies have shown that inhibition of the Mitogen-activated protein kinase (MAPK) pathway with the MEK inhibitor selumetinib (hyd-sulfate AZD6244) is an effective therapy for uveal melanoma but despite this treatment, cures are not achieved. Although drugs such as selumetinib have been studied when patients take the treatment every day, research has shown that in some cases, it may be better to use the treatment on an intermittent schedule. Such a strategy may reduce the side effects, allow higher doses of the drug to be used, more completely block the MAPK pathway, and prevent the development of drug resistance mechanisms within the tumor.
Toothpaste with 1000 ppm fluoride and above are more effective in a caries prevention in comparison to toothpastes with lower fluoride concentration or to placebo. Higher fluoride concentrations in toothpastes increase risk for development of tooth fluorosis. Children in first three years of life are most susceptible due to formation of permanent incisors and first molars in this period, beside younger children ingest more toothpaste compared to older children. Fluoride exposure can be measured in nails, where the average plasma fluoride concentration is reflected. The aim of our study was to determine fluoride concentration in fingernails and estimate if there is a correlation between fluoride concentration in fingernails and fluoride concentration in toothpaste used. In our study were included parents and children who had participated in previous studies from parenting class until children's 3 years of age. At that time children were randomly assigned to one of two groups, of which one was being given a toothpaste with 500 ppm fluoride and the other with 1000 ppm fluoride. Children were examined regularly until the age of 3. Children were invited to participate in another clinical examination at 4 years of age. At the time of examination parents were asked to fulfil a questionnaire about oral hygiene habits and a sample of children's fingernails were taken. A questionnaire fulfilled 200 parents, 169 children were examined, finger nail fluoride was analysed by using a gas chromatography method in 161 children. We determined that in 76 % the toothpaste chosen was not appropriate according to EAPD guidelines, 66 % parents was using toothpaste with 500 ppm fluoride for their children. The mean fingernail concentration was 1,43 ng/mg (SD = 0,08). The difference between groups using toothpastes with different fluoride concentrations, and compared with other factors, was not statistically significant. The mean concentration of fluoride in nails of our test group was low compared to reported values in similar studies and there was no significant difference between groups regarding to toothpaste used.

In addition, fluorosis of permanent incisors will be evaluated at 13 years of age and correlated with toothpaste fluoride concentration.