Miracle-dz/UniFAR-FTUs huggingface dataset:
Derivation of nephrogenic adenomas from renal tubular cells in kidney-transplant recipients.

BACKGROUND Nephrogenic adenomas are benign, tumor-like lesions within the urothelial mucosa of the urinary tract that are not uncommon in renal-transplant recipients. We investigated the origin of nephrogenic adenomas in renal-transplant recipients. METHODS Tissue sections were analyzed by fluorescence in situ hybridization with the use of probes for the X and Y chromosomes, by immunohistochemical methods with the use of antibodies to renal tubular antigens, and by lectin histochemical methods. Forty-six nephrogenic adenomas from 29 patients were analyzed. RESULTS All nephrogenic adenomas in 14 female recipients of transplants from male donors and 10 male recipients of transplants from female donors showed the same sex-chromosome status as the donor kidney, but not the same sex-chromosome status as the recipient's surrounding bladder tissue. The nephrogenic adenomas from all 6 female recipients of transplants from female donors showed female chromosomes, and those from the 16 male recipients of transplants from male donors showed male chromosomes. The presence of aquaporin 1, PAX2, and lectin-binding capacity for peanut agglutinin, Lotus tetragonolobus agglutinin, and Sophora japonica agglutinin in nephrogenic adenomas indicated an origin from renal tubular cells. CONCLUSIONS Nephrogenic adenomas in renal-transplant recipients are derived from tubular cells of the renal transplants and are not metaplastic proliferations of the recipient's bladder urothelium.
Prognostic impact of discordance between triple-receptor measurements in primary and recurrent breast cancer.

BACKGROUND We evaluated discordance in expression measurements for estrogen receptor (ER), progesterone receptor (PR), and HER2 between primary and recurrent tumors in patients with recurrent breast cancer and its effect on prognosis. METHODS A total of 789 patients with recurrent breast cancer were studied. ER, PR, and HER2 status were determined by immunohistochemistry (IHC) and/or FISH. Repeat markers for ER, PR, and HER2 were available in 28.9%, 27.6%, and 70.0%, respectively. Primary and recurrent tumors were classified as triple receptor-negative breast cancer (TNBC) or receptor-positive breast cancer (RPBC, i.e. expressing at least one receptor). Discordance was correlated with clinical/pathological parameters. RESULTS Discordance for ER, PR, and HER2 was 18.4%, 40.3%, and 13.6%, respectively. Patients with concordant RPBC had significantly better post-recurrence survival (PRS) than discordant cases; patients with discordant receptor status had similarly unfavorable survival as patients with concordant TNBC. IHC scores for ER and PR showed weak concordance between primary and recurrent tumors. Concordance of HER2-FISH scores was higher. CONCLUSIONS Concordance of quantitative hormone receptor measurements between primary and recurrent tumors is modest consistent with suboptimal reproducibility of measurement methods, particularly for IHC. Discordant cases have poor survival probably due to inappropriate use of targeted therapies. However, biological change in clinical phenotype cannot be completely excluded.
Outcome of in-patient falls in hospitals with 100% single rooms and multi-bedded wards.

BACKGROUND Falls in hospital account for almost two-fifths of the patient safety incidents reported to the National Reporting and Learning System in U.K. Studies have suggested an increased incidence of falls in single-bedded hospitals. OBJECTIVE To compare the outcome of in-patient falls occurring in units with 100% single rooms (SRs) and multi-bedded wards (M-BWs). SAMPLING DESIGN AND METHODS: An observational study. Retrospective standard incident reporting data (DATIX) on in-patient falls and associated injury were obtained from both sites over 18 months each. There was no change in demographics, size and characteristics of population except change in the geography of new hospitals. RESULTS The total number of in-patient fall incidents reported over the 3 years was 1,749. The mean age of patients on M-BW and SR sites was 81.0 ± 2.4 (51.3% females) and 80.3 ± 10.3 (50.7% females), respectively. The mean incidence of falls/1,000 patient-bed days on M-BW and SR sites was 5.44 ± 4.76 and 15.82 ± 19.56, respectively (P < 0.01). Overall fracture incidence/1,000 patient-bed days on M-BW and SR sites was 0.07 ± 0.48 and 0.36 ± 1.52 (P < 0.01), respectively. The hip fracture incidence/1,000 patient-bed days on M-BW and SR sites was 0.04 ± 0.38 and 0.15 ± 1.00 (P < 0.01), respectively. One-year mortality from the date of first incident fall was lower in M-BWs (41.1%) compared with SRs (47.1%), but this is not significant (P = 0.12). CONCLUSION This observational study shows a significantly increased incidence of falls and fracture in a hospital design with SRs compared with a multi-bedded facility. Consideration should be given to increased incidence of falls and falls-related injury in SRs when deciding on the percentage of single-room provision in new hospitals to admit frail older adults.
Reference values for the incremental shuttle walk test in patients with cardiovascular disease entering exercise-based cardiac rehabilitation

ABSTRACT The incremental shuttle walk test (ISWT) is used to assess functional capacity of patients entering cardiac rehabilitation. Factors such as age and sex account for a proportion of the variance in test performance in healthy individuals but there are no reference values for patients with cardiovascular disease. The aim of this study was to produce reference values for the ISWT. Participants were n = 548 patients referred to outpatient cardiac rehabilitation who underwent a clinical examination and performed the ISWT. We used regression to identify predictors of performance and produced centile values using the generalised additive model for location, scale and shape model. Men walked significantly further than women (395 ± 165 vs. 269 ± 118 m; t = 9.5, P < 0.001) so data were analysed separately by sex. Age (years) was the strongest predictor of performance in men (β = −5.9; 95% CI: −7.1 to −4.6 m) and women (β = −4.8; 95% CI: −6.3 to 3.3). Centile curves demonstrated a broadly linear decrease in expected ISWT values in males (25–85 years) and a more curvilinear trend in females. Patients entering cardiac rehabilitation present with highly heterogeneous ISWT values. Much of the variance in performance can be explained by patients’ age and sex. Comparing absolute values with age-and sex-specific reference values may aid interpretation of ISWT performance during initial patient assessment at entry to cardiac rehabilitation.
Image persistence in 1.7 μm cut-off HgCdTe focal plane arrays for SNAP

Image persistence, an elevated dark current caused by prior illumination, has been a chronic problem in near infrared focal plane arrays. It has the potential to interfere with precision photometric surveys for astronomy such as the Supernova/acceleration probe (SNAP) and other missions to study dark energy. By presenting a plausible model and supporting data, we address widespread misconceptions that persistence is a consequence of saturation and that it can be mitigated by multiple resets. Persistence increases monotonically with stimulus amplitude until the detector diodes approach forward bias, and, for the Teledyne detectors tested, is linear over most of that range, significantly improving the accuracy of calibration possible. We characterize the functional form of the temporal response, superposition of the decay curves from multiple stimuli and suppression of persistence by signal in the current frame. The effect of stimulus duration on response time constants, and the resulting scope for overly optimistic interpretation of manufacturer's data are described. Spatial variability in the amplitude and shape of the decay curve are examined. Worst case requirements for tracking prior exposure history, and some mitigation options are discussed together with practical compromises for correcting the complex behavior of persistence, given that the time required to calibrate individual pixels to sufficient accuracy is prohibitive.
Modulation of Cortical Nitric Oxide Synthase, Glutamate, and Redox State by Nifedipine and Taurine in PTZ‐kindled Mice

Summary: Purpose: Correlation between pentylenetetrazol (PTZ)‐induced kindling and the cortical nitric oxide synthase (NOS), intracellular calcium [Ca2+]i, glutamate, and free radicals was studied in mice, as well as the modulatory action of nifedipine and taurine on these parameters.
Lymphatic and Capillary Invasion Patterns in Triple Negative Breast Cancer

Triple negative breast cancer (TNBC) comprises approximately 15 to 20 per cent of all breast cancer cases. Many studies have detected less lymph node metastasis in TNBC than sporadic breast cancers. In this study, we studied capillary and lymphatic invasion in tumors of patients with TNBC. To differentiate the capillary invasion and lymphovascular invasion. We used the Anti-human CD34 and antihuman D2-40 antibodies. Antihuman CD34 antibodies stain the blood vessels and lymphatics. However, antihuman D2-40 antibodies stain lymphatics specifically. Two experienced pathologists blinded to clinical data evaluated capillary and lymphatic invasion existence in 39 TNBC patients’ tumor samples. Tumor samples were immunohistochemically stained with CD34 (endothelial cell marker) and D2–40 (podoplanin, a membrane protein, specific for lymphatic endothelium). The CD34-positive samples were categorized into two groups depending on their reaction with D2-40: lymphatic (D2-40-positive) and capillary (D2-40-negative) invasion. We have detected vascular invasion in 15 of 39 samples (38.5%) with CD34. Among those, capillary invasion was found in 14 (35.9%) and lymphatic invasion in three (7.7%) and both in two (5.1%) tumors. We did not find any significant correlation among capillary invasion, lymphatic invasion, vascular invasion, tumor grade, menopause status, history of cancer, and TNM. Capillary invasion is more commonly observed than lymphatic invasion in patients with TNBC. This finding supports the fact that more hematogenous metastasis (spreading) and less lymph node metastasis are seen in patients with TNBC.
Identification of incompletely specified multiple-valued Kleenean functions

This paper focuses on incompletely specified multiple-valued Kleenean functions (1991). It is easy to verify that they do not have functional completeness in the class of all functions on the unit interval. Therefore, not all incompletely specified functions on the unit interval are incompletely specified multiple-valued Kleenean functions. In this paper, we will clarify a necessary and sufficient condition for an incompletely specified function to be an incompletely specified multiple-valued Kleenean function. Further, we show an algorithm which derives one of the logic formulas representing the incompletely specified multiple-valued Kleenean function. In considering the application of multiple-valued Kleenean functions, we will show an example which suggests the possibility that input-output data can be described abstractly in terms of multiple-valued Kleenean functions.
Arthroscopic Brostrom Technique

Surgical strategy regarding chronic lateral ankle instability is undergoing an evolution from traditional open procedures to minimally invasive and arthroscopic techniques. The development of arthroscopic techniques for the ankle mirrors the processes witnessed for the shoulder and knee over the last 30 years. The arthroscopic Brostrom is a novel technique that allows the surgeon to use an arthroscope to perform a lateral ankle ligament reconstruction that was previously thought possible only through open surgical technique. Indications and contraindications for the arthroscopic technique are essentially the same as those for an open Brostrom type of procedure. The arthroscopic Brostrom procedure is easy to remember and relatively simple to perform for the surgeon who has mastered basic ankle arthroscopy. The authors’ results discussed in this article reveal that the arthroscopic Brostrom is a safe and effective procedure with outcomes at least equal to published results for traditional open techniques. Level of Evidence: Level V, expert opinion.
Interference with Sin3 function induces epigenetic reprogramming and differentiation in breast cancer cells

Sin3A/B is a master transcriptional scaffold and corepressor that plays an essential role in the regulation of gene transcription and maintenance of chromatin structure, and its inappropriate recruitment has been associated with aberrant gene silencing in cancer. Sin3A/B are highly related, large, multidomian proteins that interact with a wide variety of transcription factors and corepressor components, and we examined whether disruption of the function of a specific domain could lead to epigenetic reprogramming and derepression of specific subsets of genes. To this end, we selected the Sin3A/B-paired amphipathic α-helices (PAH2) domain based on its established role in mediating the effects of a relatively small number of transcription factors containing a PAH2-binding motif known as the Sin3 interaction domain (SID). Here, we show that in both human and mouse breast cancer cells, the targeted disruption of Sin3 function by introduction of a SID decoy that interferes with PAH2 binding to SID-containing partner proteins reverted the silencing of genes involved in cell growth and differentiation. In particular, the SID decoy led to epigenetic reprogramming and reexpression of the important breast cancer-associated silenced genes encoding E-cadherin, estrogen receptor α, and retinoic acid receptor β and impaired tumor growth in vivo. Interestingly, the SID decoy was effective in the triple-negative M.D. Anderson-Metastatic Breast-231 (MDA-MB-231) breast cancer cell line, restoring sensitivity to 17β-estradiol, tamoxifen, and retinoids. Therefore, the development of small molecules that can block interactions between PAH2 and SID-containing proteins offers a targeted epigenetic approach for treating this type of breast cancer that may also have wider therapeutic implications.
Comparison of transarterial and multiple nerve stimulation techniques for axillary block using a high dose of mepivacaine with adrenaline

Background: High‐dose transarterial (TA) technique results in high effectiveness of the axillary block. The technique is fast and simple, but does not produce a satisfactory success rate when using the manufacturer’s recommended dose of mepivacaine. The multiple nerve stimulation (MNS) technique requires more time and experience. This double‐blind study compared effectiveness, safety and the time used to obtain an effective analgesia in 101 patients, having an axillary block by either TA or MNS techniques.
The Schizosaccharomyces pombe Pzh1 protein phosphatase regulates Na+ ion influx in a Trk1-independent fashion.

We have previously shown that fission yeast encodes a PPZ-like phosphatase, designated Pzhl, which is an important determinant of cation homeostasis. pzh1 delta mutants display increased tolerance to Na+ ions, but they are hypersensitive to KC1 [Balcells, L. , Gómez, N. , Casamayor, A. , Clotet, J. & Ariño, J. (1997) Eur. J. Biochem. 250, 476-483]. We have immunodetected Pzh1 in yeast extracts and found that this phosphatase is largely associated with particulate fractions. Cells defective in Pzh1 do not show altered efflux of Na+ or Li+ ions, but they accumulate these cations more slowly than wild-type cells. K+ ion content of pzh1 delta cells is about twice that of wild-type cells, and this can be explained by decreased efflux of K+. Therefore, Pzh1 may regulate both Na+ influx and K+ efflux in fission yeast. To test the possible relationship between K+ uptake, Na+ tolerance and Pzh1 function, we deleted the trk1+ gene, which encodes a putative high-affinity transporter of K+ ions. trkl delta mutants grew well even at relatively low concentrations of KCl and did not show significantly altered content or influx of K+ ions. However, they showed a Na(+)-sensitive phenotype which was greatly intensified by deletion of the sod2+ gene (which encodes the major determinant for efflux of Na+ ions), and clearly ameliorated by deletion of the pzh1 phosphatase, as well as by moderate concentrations of KCl in the medium. These results suggest that Trk1 does not mediate the effect of Pzh1 on NaCl tolerance and that fission yeast contains efficient systems, other than Trk1, for uptake of K+ ions.
Outer membrane lipid homeostasis via retrograde phospholipid transport in Escherichia coli

Biogenesis of the outer membrane (OM) in Gram-negative bacteria, which is essential for viability, requires the coordinated transport and assembly of proteins and lipids, including lipopolysaccharides (LPS) and phospholipids (PLs), into the membrane. While pathways for LPS and OM protein assembly are well-studied, how PLs are transported to and from the OM is not clear. Mechanisms that ensure OM stability and homeostasis are also unknown. The trans-envelope Tol-Pal complex, whose physiological role has remained elusive, is important for OM stability. Here, we establish that the Tol-Pal complex is required for PL transport and OM lipid homeostasis in Escherichia coli. Cells lacking the complex exhibit defects in lipid asymmetry and accumulate excess phospholipids (PLs) in the OM. This imbalance in OM lipids is due to defective retrograde PL transport in the absence of a functional Tol-Pal complex. Thus, cells ensure the assembly of a stable OM by maintaining an excess flux of PLs to the OM only to return the surplus to the inner membrane. Our findings also provide insights into the mechanism by which the Tol-Pal complex may promote OM invagination during cell division.
STAT3 phosphorylation in injured axons before sensory and motor neuron nuclei: Potential role for STAT3 as a retrograde signaling transcription factor

STAT3 is a latent transcription factor that is activated by plasma membrane growth factor receptor complexes. Conditional gene disruption data indicate that it contributes to the survival of cranial motor neurons after peripheral nerve lesion. In agreement, levels of activated STAT3 (Tyr705‐phosphorylated STAT3) have been shown to increase in the nuclei of adult cranial motor neurons during their regeneration after the same injury. The data presented here demonstrate that STAT3 is similarly but not identically affected in sciatic motor neurons after sciatic nerve injury. In addition, we find that sensory neuron nuclei also display an analogous increase in activated STAT3, thereby supporting a role for STAT3 in the survival and regeneration of these cells. Most interesting, the present data indicate that peripheral nerve lesion leads to a very rapid activation of STAT3 in axons at the lesion site. This response increases during the first 24 hours after injury and extends back to the motor and sensory neurons such that phospho‐STAT3–immunoreactive axons are first detected in the dorsal root ganglia and ventral spinal cord at the same postlesion time intervals at which the activated STAT3 is first detected in the neuronal nuclei. Together these data raise the possibility that axonal STAT3, activated at the injury site, acts as a retrograde signaling transcription factor, which promotes the survival and regeneration of both sensory and motor neurons. J. Comp. Neurol. 474:535–545, 2004. © 2004 Wiley‐Liss, Inc.
Clinical outcomes in t(4;14) multiple myeloma: a chemotherapy-sensitive disease characterized by rapid relapse and alkylating agent resistance.

PURPOSE To determine whether primary drug resistance or rapid relapse explains the poor prognosis seen in t(4;14)-positive multiple myeloma (MM). PATIENTS AND METHODS A total of 131 patients treated with high-dose therapy (HDT) were assessed, of whom 19 were t(4;14) positive. We examined the presentation features, chemotherapy responsiveness at presentation and to salvage therapies at relapse, and overall survival outcomes. RESULTS t(4;14)-positive patients had a predominance of the immunoglobulin A isotype (52.6%) but otherwise baseline characteristics were indistinguishable. After treatment with vincristine, doxorubicin, and dexamethasone or dexamethasone alone, 17 (89.7%) of the 19 patients achieved a partial response and 11 patients (57.9%) demonstrated an additional 50% reduction in paraprotein after HDT. Thus, t(4;14)-positive patients are chemotherapy sensitive; however, early progression was common, with 26% of patients progressing before HDT and a median progression-free survival after HDT of only 14.1 months. At relapse, a resistance to alkylating agents was evident, with no responses (zero of 11 patients) seen with conventional-dose alkylating agents. Salvage regimens using thalidomide and/or dexamethasone achieved at least minimal response in 59% of patients. The duration of response was short, however, with a median of only 4.7 months. The median overall survival after HDT was 24.2 months. CONCLUSION We conclude that t(4;14)-positive MM is chemotherapy sensitive but rapid relapse occurs. Resistance to alkylating agents is evident at relapse. The development of novel therapeutic agents is required, including the early clinical study of targeted fibroblast growth factor receptor 3 tyrosine kinase inhibitors, which have shown promise in preclinical studies.
In Vitro Bone Production Using Stem Cells Derived From Human Dental Pulp

To harvest bone for autologous grafting is a daily problem encountered by craniofacial and oral surgeons. Stem cells derived from human dental pulp are able to differentiate in osteoblasts and are a potential source of autologous bone produced in vitro. The authors describe their preliminary results in this new field with its potential application in craniomaxillofacial surgery. Dental pulp was gently extracted from 34 human permanent teeth (all third molars) of patients 19 to 37 years of age. After they were digested, the cells were selected using a cytometer for c-kit, STRO-1, CD34, CD45, and then for CD44 and RUNX-2. This study, made on a considerable number of cases, provided evidence that dental pulp is extremely rich in stem cells, which were c-kit+/CD34+/STRO-1+/CD45−, capable of differentiation toward several stromal-derived differentiated cells and mainly osteoblasts. These findings, supported by the large number of cases, are of great interest for tissue regeneration, tissue-based clinical therapies, and transplantation.
A Functional Complex of Adenovirus Proteins E1B-55kDa and E4orf6 Is Necessary To Modulate the Expression Level of p53 but Not Its Transcriptional Activity

ABSTRACT In adenovirus-infected cells, binding of E1B-55kDa and E4orf6 to the tumor suppressor protein p53 inhibits its transcriptional activity and causes rapid turnover of the protein. To investigate the requirements of the E1B-E4orf6 complex to modulate p53 function, we generated an E4orf6 mutant that failed to associate functionally and physically with E1B-55kDa but still interacted with p53. We confirm that E4orf6 and E1B-55kDa reduce p53 transactivation individually and show that their combined inhibition is additive rather than synergistic. Furthermore, we found that downregulation of p53's expression level, but not transcriptional inhibition of p53, depends on a functional E1B-E4 complex. A functional interaction of E1B-55kDa with p53, on the other hand, is a prerequisite for both transcriptional repression and downregulation of p53. The separation of these two functions will enable further dissection of the requirements for oncogenicity by the E4orf6 protein.