Miracle-dz/UniFAR-FTUs huggingface dataset:
Urinary excretion of cyclophosphamide in humans, determined by phosphorus-31 nuclear magnetic resonance spectroscopy.

Phosphorus-31 NMR spectroscopy was used to analyze urine samples from patients treated with cyclophosphamide (CP) on 2 consecutive days. CP and all of its known phosphorylated metabolites except the tautomeric pair 4-hydroxycyclophosphamide/aldophosphamide, i.e. carboxycyclophosphamide (CXCP), dechloroethylcyclophosphamide (DCCP), alcophosphamide, ketophosphamide, and phosphoramide mustard (PM), were determined. Several other signals corresponding to unknown CP-related compounds were observed. Seven of them were identified; all were hydrolysis products of CP or its metabolites (one from CP, two from CXCP, three from DCCP, and one from PM). Twenty-four-hour urinary excretion of unmetabolized CP was not significantly different on the first (17% of the daily administered dose) and second (16%) days of treatment. The amounts of phosphorylated metabolites excreted in 24-hr urine samples were much higher after the second CP dose (37%) than after the first (20%), suggesting autoinduction of CP metabolism. CXCP and its two degradation products (accounting for 7-10% of CXCP) were by far the major metabolites (11.5 and 23% after the first and second doses, respectively). DCCP plus its degradation products and alcophosphamide each represented 2-3% on the first day of treatment and 5% on the second day of treatment. Levels of PM and its degradation products were extremely low (0.3 and 0.6% after the first and second CP doses, respectively), as were those of ketophosphamide (0.4 and 0.6% on the first and second days of treatment, respectively). We noted only modest interpatient variation in excreted levels of CP and all of its metabolites.
A multicenter clinical study evaluating the confirmed complete molecular response rate in imatinib-treated patients with chronic phase chronic myeloid leukemia by using the international scale of real-time quantitative polymerase chain reaction

Achievement of complete molecular response in patients with chronic phase chronic myeloid leukemia has been recognized as an important milestone in therapy cessation and treatment-free remission; the identification of predictors of complete molecular response in these patients is, therefore, important. This study evaluated complete molecular response rates in imatinib-treated chronic phase chronic myeloid leukemia patients with major molecular response by using the international standardization for quantitative polymerase chain reaction analysis of the breakpoint cluster region-Abelson1 gene. The correlation of complete molecular response with various clinical, pharmacokinetic, and immunological parameters was determined. Complete molecular response was observed in 75/152 patients (49.3%). In the univariate analysis, Sokal score, median time to major molecular response, ABCG2 421C>A, and regulatory T cells were significantly lower in chronic phase chronic myeloid leukemia patients with complete molecular response than in those without complete molecular response. In the multivariate analysis, duration of imatinib treatment (odds ratio: 1.0287, P=0.0003), time to major molecular response from imatinib therapy (odds ratio: 0.9652, P=0.0020), and ABCG2 421C/C genotype (odds ratio: 0.3953, P=0.0284) were independent predictors of complete molecular response. In contrast, number of natural killer cells, BIM deletion polymorphisms, and plasma trough imatinib concentration were not significantly associated with achieving a complete molecular response. Several predictive markers for achieving complete molecular response were identified in this study. According to our findings, some chronic myeloid leukemia patients treated with imatinib may benefit from a switch to second-generation tyrosine kinase inhibitors (ClinicalTrials.gov, UMIN000004935).
PROSPECTIVE COMPARISON BETWEEN SEDATED HIGH‐DEFINITION ORAL AND UNSEDATED ULTRATHIN TRANSNASAL ESOPHAGOGASTRODUODENOSCOPY IN THE SAME SUBJECTS: PILOT STUDY

Background: Recently, quality as well as acceptability has been a concern regarding endoscopy. The aim of the present study was to compare the acceptability and quality of sedated high‐definition esophagogastroduodenoscopy (sHD‐EGD) using a newly developed high‐definition videoscope with those of unsedated ultrathin esophagogastroduodenoscopy (uUT‐EGD) using a 5.2 mm videoscope.
Optical coherence tomography and autofluorescence findings in areas with geographic atrophy due to age-related macular degeneration.

PURPOSE To analyze outer retinal changes within the atrophic lesion in patients with geographic atrophy (GA) secondary to age-related macular degeneration. METHODS Twenty-one simultaneously obtained fundus autofluorescence (FAF, excitation, 488 nm; emission, 500-700 nm) and spectral-domain optical coherence tomography (SD-OCT) scans (Spectralis HRA+OCT; Heidelberg Engineering, Heidelberg, Germany) of 21 GA patients (mean age, 75.1 ± 7.4 years) were included and separately exported. Two readers independently graded the following parameters: width of the atrophic lesion on the FAF image at the site where the SD-OCT scan had been placed; and on the SD-OCT image, widths of the linear disruption of the outer nuclear layer, the external limiting membrane, and the inner and outer segments of the photoreceptor layer (IPRL) and width of the disruption of choroidal signal enhancement. Results. The mean width of the atrophic lesion by FAF imaging was 2.83 mm (95% confidence interval, 2.37-3.29). The linear disruption of choroidal hyperreflectivity showed the closest agreement with 2.83 mm (2.37-3.28), whereas the linear width of disrupted IPRL was larger (3.10 mm; 2.65-3.55). Overall, the width of the atrophic lesion correlated significantly with all five SD-OCT parameters (P < 0.0001, r = 0.96-0.99). CONCLUSIONS These findings demonstrate that the atrophic lesions identified with FAF represent irreversible underlying outer retinal damage. The observation that the width of the atrophic lesion identified with FAF, although significantly correlated but not identical with the width of disruption within the cellular layers of the retina, is consistent with the dynamic nature of the disease. (ClinicalTrials.gov numbers, NCT00393692, NCT00599846.).
Properties and functional roles of hyperpolarization‐gated currents in guinea‐pig retinal rods

1 The inward rectification induced by membrane hyperpolarization was studied in adult guinea‐pig rods by the perforated‐patch‐clamp technique. 2 CsCl blocked the rectification observed in both voltage‐ and current‐clamp recordings at voltages negative to −60 mV, while BaCl2 blocked the inward relaxation observed at voltages positive to −60 mV. The current activated at −90 mV had a low selectivity between sodium and potassium and reversed at −31.0 mV. 3 These observations suggest that two inward rectifiers are present in guinea‐pig rods: a hyperpolarization‐activated (Ih) and a hyperpolarization‐deactivated (Ikx) current. The functional roles of Ih and Ikx were evaluated by stimulating rods with currents sinusoidally modulated in time. 4 Rods behave like bandpass amplifiers, with a peak amplification of 1.5 at about 2 Hz. For hyperpolarizations that mainly gate Ikx, amplification and phase shifts are fully accounted for by a rod membrane analogue model that includes an inductance. For hyperpolarizations that also gate Ih, a harmonic distortion became apparent. 5 Bandpass filtering and amplification of rod signals, associated with Ih and Ikx gating by membrane hyperpolarization, are strategically located to extend, beyond the limits imposed by the slow phototransductive cascade, the temporal resolution of signals spreading to the rod synapse.
Radiographic Study of the Fifth Metatarsal for Optimal Intramedullary Screw Fixation of Jones Fracture

Background: Jones fractures occur in the relatively avascular metadiaphyseal junction of the fifth metatarsal (MT), which predisposes these fractures to delayed union and nonunion. Operative treatment with intramedullary (IM) screw fixation is recommended in certain cases. Incorrect screw selection can lead to refractures, nonunion, and cortical blowout fractures. A better understanding of the anatomy of the fifth MT could aid in preoperative planning, guide screw size selection, and minimize complications. Methods: We retrospectively identified foot computed tomographic (CT) scans of 119 patients that met inclusion criteria. Using interactive 3-dimensional (3-D) models, the following measurements were calculated: MT length, “straight segment length” (distance from the base of the MT to the shaft curvature), and canal diameter. Results: The diaphysis had a lateroplantar curvature where the medullary canal began to taper. The average straight segment length was 52 mm, and corresponded to 68% of the overall length of the MT from its proximal end. The medullary canal cross-section was elliptical rather than circular, with widest width in the sagittal plane and narrowest in coronal plane. The average coronal canal diameter at the isthmus was 5.0 mm. A coronal diameter greater than 4.5 mm at the isthmus was present in 81% of males and 74% of females. Conclusion: To our knowledge, this is the first anatomic description of the fifth metatarsal based on 3-D imaging. Excessive screw length could be avoided by keeping screw length less than 68% of the length of the fifth metatarsal. A greater than 4.5 mm diameter screw might be needed to provide adequate fixation for most study patients since the isthmus of the medullary canal for most were greater than 4.5 mm. Clinical Relevance: Our results provide an improved understanding of the fifth metatarsal anatomy to guide screw diameter and length selection to maximize screw fixation and minimize complications.
Cutaneous Wound Healing: Myofibroblastic Differentiation and in Vitro Models

Wound healing is an interactive, dynamic 3-phased process. During the formation of granulation tissue, many fibroblastic cells acquire some morphological and biochemical smooth muscle features and are called myofibroblasts. Myofibroblasts participate in both granulation tissue formation and remodeling phases. Excessive scarring, which is a feature of impaired healing, is a serious health problem that may affect the patient's quality of life. The treatment costs of such lesions are high, and often, the results are unsatisfactory. To understand the wound healing process better and to promote improvement in human healing, models are needed that can predict the in vivo situation in humans. In vitro models allow the study of cell behavior in a controlled environment. Such modeling partitions and reduces to small scales behavior perceived in vivo. This article is focused on `fibroblasts. ' In vitro models to study wound healing, the role of (myo)fibroblasts, and skin reconstruction in tissue replacement and promotion of wound healing are discussed.
How much weight gain occurs following smoking cessation? A comparison of weight gain using both continuous and point prevalence abstinence.

Estimates of postcessation weight gain vary widely. This study determined the magnitude of weight gain in a cohort using both point prevalence and continuous abstinence criteria for cessation. Participants were 196 volunteers who participated in a smoking cessation program and who either continuously smoked (n = 118), were continuously abstinent (n = 51), or who were point prevalent abstinent (n = 27) (i.e., quit at the 1-year follow-up visit but not at others). Continuously abstinent participants gained over 13 lbs. (5.90 kg) at 1 year, significantly more than continuously smoking (M = 2.4 lb.) and point prevalent abstinent participants (M = 6.7 lbs., or 3.04 kg). Individual growth curve analysis confirmed that weight gain and the rate of weight gain (pounds per month) were greater among continuously smoking participants and that these effects were independent of gender, baseline weight, smoking and dieting history, age, and education. Results suggest that studies using point prevalence abstinence to estimate postcessation weight gain may be underestimating postcessation weight gain.
HCV chronic hepatitis in patients with HIV: clinical management issues

HIV-hepatitis C virus (HCV) coinfection is common and affects more than one-third of all HIV infected persons worldwide. Prevalence among risk categories varies according to shared risk factors for transmission, mainly intravenous drug use (IDU) and hemophiliacs. Chronic HCV infection seems to accelerate the course of HIV disease, resulting in a worsened clinical and immunological progression. At the same time, several studies suggest that HIV disease modifies the natural history of HCV infection, leading to a faster course of progression from active hepatitis to cirrhosis, to end stage liver disease and death. HCV infection mimics opportunistic diseases because its natural history is significantly accelerated in HIV patients. Since highly active antiretroviral therapy (HAART) has slowed the progression of HIV disease and decreased the rate of HIV associated mortality, the prognosis of HIV disease has been modified, and the need to treat HCV coinfection become a significant issue. Because of the poor response rate obtained by either interferon alone or interferon thrice weekly plus ribavirin, the combination of pegylated interferon and ribavirin will probably become the standard of care, although the clinicians should be aware of the overlapping toxicity of nucleoside analogues and ribavirin. Many selected categories of patients pose particular challenges to physicians treating HCV infection: nonresponders to interferon, cirrhotic patients, and patients infected with both HCV and HBV. Liver transplantation in HIV patients is currently under evaluation, but should become the rescue therapy for HIV patients with end stage liver disease.
Calcified Amyloid Tumor of Neck with Exuberant Giant Cell Reaction

Amyloidosis is a group of disorders characterized by an extracellular deposition of an abnormal amount of proteins in a variety of organs resulting from abnormal folding of protein. It typically presents as disseminated deposits. Tumor like localized presentation of amyloidosis in the absence of systemic amyloidosis is referred to as amyloidoma or amyloid tumor. Amyloidoma is the least common presentation of tissue amyloid deposition. Amyloidoma of soft tissue is again a very rare entity, especially in the neck region. Calcification and minimum giant cell reaction can occur in amyloidoma. However, extensive calcification and exuberant giant cell reaction in amyloidoma of soft tissue neck make it difficult to diagnose. In this report, we discuss such a rare case with its differential diagnoses.
The importance of mini-puberty for fertility in cryptorchidism.

PURPOSE Mini-puberty is the hormonal surge of gonadotropins and testosterone which occurs in early infancy. It induces the development and transformation of gonocytes into Ad spermatogonia, which is impaired in many cryptorchid testes. We examine the role of testosterone in the transformation and development of Ad spermatogonia. MATERIALS AND METHODS A total of 32 patients 1 to 7 years old were treated with human chorionic gonadotropin (HCG) to achieve epididymo-testicular descent before orchiopexy (group 1), and 33 patients underwent orchiopexy without previous hormonal treatment (group 2). A testicular biopsy was obtained during surgery from all the patients. The number of Ad spermatogonia per tubular cross section (Ad/tbx) was assessed and compared between the 2 groups. The number of Ad spermatogonia per tubular cross section in group 1 was also correlated with the post-stimulatory testosterone plasma values. RESULTS In group 1, 17 patients had greater than 0.1 Ad/tbx, and the remaining patients had 0.1 or less Ad/tbx. In group 2, 6 patients had greater than 0.1 Ad/tbx. Of the boys with cryptorchidism 35% responded inadequately to HCG stimulation, while 10% did not respond. Those patients with suboptimal Leydig cell capacity (and an inadequate response to HCG stimulation) had a defective Ad spermatogonia differentiation of 0.1 or less. CONCLUSIONS Boys with cryptorchidism with an insufficient testosterone surge after HCG risk infertility despite early and successful surgery. The testicular biopsy assists in identifying those who might benefit from hormonal treatment following successful orchiopexy.
Intergovernmental Fiscal Transfers and Local Incentives and Responses: The Case of Indonesia

Indonesian policymakers are convinced that a number of perverse incentives are embedded in their system of intergovernmental transfers. Officials in countries throughout the developing world have similar views about their own intergovernmental frameworks. In Indonesia, perverse incentives are thought to negatively influence a wide range of local government fiscal behaviours, including as regards own-source revenues, spending and savings. An empirical analysis of the local government response to transfers, however, offers only mixed support for the existence and strength of the presumed incentives. Overall, the findings in this paper highlight the benefits to central governments of rigorously examining assumed perverse incentives in their intergovernmental frameworks before embarking on attempts to expunge them.
Effect of dentin-cleaning techniques on the shear bond strength of self-adhesive resin luting cement to dentin.

OBJECTIVE This in vitro study evaluated the influence of different cleansing techniques on the bond strength of self-adhesive cement to dentin. METHODS AND MATERIALS A total of 33 noncarious human molars were sectioned mesiodistally and embedded in chemically cured resin with the buccal or lingual surfaces facing upward. Superficial dentin was exposed and resin disk provisional restorations were cemented to the dentin surfaces with noneugenol provisional cement and were stored in distilled water at 37°C. After seven days, the provisional restorations were removed and 13 specimens were randomly assigned to each of the five groups (n=13), according to the following cleansing treatments: G1-excavator (control); G2-0.12% chlorhexidine digluconate; G3-40% polyacrylic acid; G4-mixture of flour pumice and water; and G5-sandblasting with 50 μm aluminum oxide particles at a pressure of 87 psi. Resin composite disks (Filtek Supreme Plus, 3M ESPE Dental Products, St Paul, MN, USA) 4.7 (±0.1) mm in diameter and 3.0 (±0.5) mm in height were cemented with self-adhesive cement (RelyX Unicem, 3M ESPE), photocured, and stored in distilled water at 37°C for 24 hours. Shear bond strength testing was conducted using a universal test machine at a crosshead speed of 0.5 mm/min until failure. RESULTS Data were analyzed using analysis of variance (ANOVA) and the Tukey-B rank order test. Sandblasting with aluminum oxide (11.32 ± 1.70 MPa) produced significantly higher shear bond strength values compared with any other treatment groups (p<0.05). No significant differences were found between G1-control (7.74 ± 1.72 MPa), G2-chlorhexidine (6.37 ± 1.47 MPa), and G4-pumice (7.33 ± 2.85 MPa) (p<0.05).
Business Cycles and the Cross-Section of Currency Returns

We show that business cycles are a key driver of currency excess returns: strong economies offer high returns while weak economies offer low or negative returns, which holds both inand out-of-sample. Surprisingly, the returns stem primarily from spot exchange rate predictability and are uncorrelated with common currency strategies. Moreover, a business cycle factor that captures the spread in economic conditions across countries is priced in cross-sections of currency excess returns arising from carry, momentum and value strategies. We discuss the implications of these results for international macro-finance theory and for global investors seeking novel sources of currency portfolio diversification.
Asymmetric Consumption Effects of Transitory Income Shocks

We use the responses of a representative sample of Dutch households to survey questions that ask how much their consumption would change in response to unexpected, transitory income shocks (positive or negative). The questionnaire also distinguishes between relatively small income changes (a one-month increase or drop in income), and relatively larger ones (equal to three-months' income). The results are broadly in line with models of intertemporal choice with precautionary saving, borrowing constraints and finite horizons.
The C-terminal domain is essential for protective activity of the Bordetella pertussis adenylate cyclase-hemolysin

The adenylate cyclase-hemolysin of Bordetella pertussis consists of a cell-invasive N-terminal adenylate cyclase domain linked to a C-terminal RTX hemolysin containing extensive glycine-rich repeats. The toxin is an essential virulence factor required in the initial stages of infection. Adenylate cyclase-hemolysin was also shown to be a potent vaccinating antigen inducing protection against B. pertussis colonization of the mouse respiratory tract. This protective activity depends on a posttranslational fatty-acylation modification. We used a set of deletion derivatives of the recombinant adenylate cyclase-hemolysin to localize the protective epitopes on the 1,706-residue toxin. We show that specific anti-adenylate cyclase-hemolysin antibodies present in the sera of B. pertussis-infected mice and humans are directed predominantly against the modification-and-repeat portion of the toxin, contained in the last 800 residues of the adenylate cyclase-hemolysin. These antibodies appear to recognize conformational epitopes present only in a structure formed by the intact C-terminal half of the toxin. There was no correlation between the capacity of the truncated adenylate cyclase-hemolysin derivatives to induce both toxin-neutralizing antibodies upon immunization of mice and protective immunity. However, only the truncated proteins which were recognized by the sera of infected mice and humans and which had their last 800 residues intact had the capacity to induce protection of mice against colonization by B. pertussis. This indicates that the structure of the modification-and-repeat region of adenylate cyclase-hemolysin is critical for its protective activity.
Dynamic Information in the Identification and Discrimination of Vowels

Abstract The dynamic theory of vowel perception emphasizes the importance of the consonant transitions in CVC syllables to the identification of the vowel itself. However, the dynamic theory is relatively vague in terms of what perceptual processes may be involved and it says nothing about the role of auditory and/or phonetic memory for such ‘dynamic events’. The present study created three synthetic [É]-[ε] continua consisting of a [b Vb] full-syllable continuum, a silent-center continuum (which had over 72% of the medial vowel replaced by silence) and an isolated vowel continuum to specifically examine (1) the use of auditory and phonetic memory for dynamic acoustic cues and (2) the ability of listeners to track the trajectories of very brief formant transitions. Experiment 1 demonstrated that there were no significant differences among the three continua in terms of listener identifications but that the silent-center tokens demonstrated significantly lower within-category discriminations, perhaps because of degraded auditory representation. Experiment 2 required listeners to make cross-continuum vowel discriminations and showed that some degree of acoustic similarity was important – listeners were particularly poor at discriminating between the silent-center and vowel-only tokens. This suggests that listeners were not able to make discriminations on the basis of abstract vowel labels alone. Experiment 3 demonstrated that listeners could make quite accurate vowel identifications even when as little as 1 pitch period of acoustic energy signaled the consonant transitions in the silent-center tokens. Experiment 4 showed that listeners’ identifications of the silent-center stimuli were based on the formant changes in the transitions rather than their endpoint frequencies.