Miracle-dz/UniFAR-FTUs huggingface dataset:
Harmonization of glutamic acid decarboxylase and islet antigen-2 autoantibody assays for national institute of diabetes and digestive and kidney diseases consortia.

BACKGROUND/RATIONALE Autoantibodies to islet antigen-2 (IA-2A) and glutamic acid decarboxylase (GADA) are markers for diagnosis, screening, and measuring outcomes in National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) consortia studies. A harmonization program was established to increase comparability of results within and among these studies. METHODS Large volumes of six working calibrators were prepared from pooled sera with GADA 4.8-493 World Health Organization (WHO) units/ml and IA-2A 2-235 WHO units/ml. Harmonized assay protocols for IA-2A and GADA using (35)S-methionine-labelled in vitro transcribed and translated antigens were developed based on methods in use in three NIDDK laboratories. Antibody thresholds were defined using sera from patients with recent onset type 1 diabetes and healthy controls. To evaluate the impact of the harmonized assay protocol on concordance of IA-2A and GADA results, two laboratories retested stored TEDDY study sera using the harmonized assays. RESULTS The harmonized assays gave comparable but not identical results in the three laboratories. For IA-2A, using a common threshold of 5 DK units/ml, 549 of 550 control and patient samples were concordantly scored as positive or negative, specificity was greater than 99% with sensitivity 64% in all laboratories. For GADA, using thresholds equivalent to the 97th percentile of 974 control samples in each laboratory, 1051 (97.9%) of 1074 samples were concordant. On the retested TEDDY samples, discordance decreased from 4 to 1.8% for IA-2A (n = 604 samples; P = 0.02) and from 15.4 to 2.7% for GADA (n = 515 samples; P < 0.0001). CONCLUSION Harmonization of GADA and IA-2A is feasible using large volume working calibrators and common protocols and is an effective approach to ensure consistency in autoantibody measurements.
Allogeneic stem cell transplantation for children with acquired severe aplastic anaemia: a retrospective study by the Viva‐Asia Blood and Marrow Transplantation Group

We retrospectively analysed the outcomes of 127 children with acquired severe aplastic anaemia (SAA) who had received haematopoietic stem cell transplantation (HSCT) between 2000 and 2011 in one of the 10 Asia Pacific institutions. Fifty‐three were matched sibling donor (MSD) and 74 were alternative donor (AD), including 22 matched unrelated donor, 32 mismatched unrelated donor and 20 mismatched related donor. With a median follow up 45·5 months (13–139) and when compared to the MSD group, AD recipients had more grade II‐IV acute graft‐versus‐host disease (aGVHD; 14·3% vs. 32·8%, P = 0·029), but similar grade III‐IV aGVHD (10·2% vs. 12·5%, P = 0·774), graft failure (GF) (15·1% vs. 15·5%, P = 0·658) and 5‐year overall survival (90·6% vs. 83·7%, P = 0·251). As a source of stem cell, peripheral blood stem cells (PBSC) resulted in less GF (18% vs. 9·1% P = 0·013), similar grade II‐IV aGVHD (28·1% vs. 17·4%, P = 0·258), chronic GVHD (25·8% vs. 29·3%, P = 0·822) and similar outcomes (89·7% vs. 82·4%, P =0 ·665) when compared to bone marrow (BM). In univariate analysis, GF (P < 0·001) and grade II‐IV aGVHD (P = 0·009) were predictors of poor survival. In multivariate analysis, only GF was associated with poor survival (P = 0·012). The outcome of AD and PBSC HSCT were comparable to that of MSD and BM HSCT in the Asia Pacific region.
Further Results on T-Coloring and Frequency Assignment Problems

A graph coloring problem (called T-coloring) is investigated in which integers are assigned to the vertices of a graph G, under the constraint that the absolute value of the difference between integers assigned to adjacent vertices does not belong to a forbidden set (called the T-set). The T-coloring problem has applications in the radio frequency channel assignment problem. T-sets of the form $\{0,s,23,\ldots,ks\}\cup S$, where $s,k\geq 1$ and $S\supseteq\{s+1,s+2,\ldots,ks-1\}$, are considered. This set has been named the k-multiple of s set. Values of interest are the minimum cardinality, $\chi_T(G)$, and the minimum span ${\rm sp}_T(G)$, of the set of assigned integers, over all possible T-colorings of G. A greedy algorithm, which T-colors perfectly orderable graphs in $\chi_T(G)$ colors with span ${\rm sp}_T(G)$ (for a k-multiple of s set), is given.
Increased prevalence of psychopathology and maladaptive personality traits after long-term cure of Cushing's disease.

CONTEXT AND OBJECTIVE Psychopathology and maladaptive personality traits are often observed during the active phase of Cushing's disease (CD). We hypothesized that patients with long-term cure of CD show persistent psychopathology and maladaptive personality traits. DESIGN Four questionnaires on frequently occurring psychopathology in somatic illnesses were used, including the Apathy Scale, Irritability Scale, Hospital Anxiety and Depression Scale, and Mood and Anxiety Symptoms Questionnaire short-form. Personality was assessed using the Dimensional Assessment of Personality Pathology short-form (DAPPs). PATIENTS AND CONTROL SUBJECTS We included 51 patients cured of CD (16% men, 53 ± 13 yr) and 51 matched controls. In addition, we included 55 patients treated for nonfunctioning pituitary macroadenomas (55% men, 62 ± 10 yr), and 55 matched controls. RESULTS Mean duration of remission was 11 yr (range 1-32 yr). Compared with matched controls, patients cured from CD scored significantly worse on virtually all questionnaires. Compared with nonfunctioning pituitary macroadenoma patients, patients treated for CD scored worse on apathy (P < 0.001), irritability (P < 0.001), anxiety (P < 0.001), negative affect and lack of positive affect (P < 0.001 on both scales), somatic arousal (P < 0.001), and 11 of 18 subscales of the Dimensional Assessment of Personality Pathology short-form (P < 0.05). CONCLUSIONS Patients with long-term cured CD show an increased prevalence of psychopathology and maladaptive personality traits. These observations suggest irreversible effects of previous glucocorticoid excess on the central nervous system rather than an effect of pituitary tumors and/or their treatment in general. This may also be of relevance for patients treated with high doses of exogenous glucocorticoids.
Information: The Key to Health Service Quality

Total quality management (TQM) is one of many new quality initiatives being introduced in the NHS to improve the quality of information and overall service quality. Out‐patient departments were targeted by the Department of Health as an area in which to start quality improvements, particularly regarding the provision of information to patients. Describes a study undertaken in a rheumatology out‐patients clinic which examined the flow of information, where information can be improved and how TQM can help improvement. Based on the hypothesis that patients′ and staff′s perceptions of information quality differ to the extent that some patients are not satisfied with information quality and this is inconsistent with a TQM approach. The quality of information was measured in three areas: sufficiency, understanding, and selectivity. A structured questionnaire was used and 80 patients and 11 staff were interviewed. Discusses differences in perceptions of information. Further research is needed to make a detailed study of information flow and to identify specific areas of information provision for improvement.
Evaluating gene expression profiling by quantitative polymerase chain reaction to develop a clinically feasible test for outcome prediction in multiple myeloma

The gene expression profiles (GEPs) of 96 selected genes were analysed by real‐time quantitative polymerase chain reaction (qPCR) with a TaqMan low‐density array card in isolated tumour plasma cells (PCs) from 157 newly diagnosed multiple myeloma (MM) patients. This qPCR‐based GEP correctly classified cases following the Translocation‐cyclin D classification. Classic prognostic parameters and qPCR‐based GEP predicted MM patient outcome and, although multivariate analyses revealed that cytogenetic risk (standard vs. high risk) was the variable that most strongly predicted prognosis, GEP added significant information for risk stratification. Considering only the standard risk cytogenetic patients, multivariate analyses revealed that high β2‐microglobulin, low CDKN1A and high SLC19A1 gene expression levels independently predicted a short time‐to‐progression (TTP), while high International Staging System stage, low CDKN2B and high TBRG4 gene expression predicted poor overall survival (OS). A gene expression risk score enabled the division of standard risk patients into two groups with different TTPs (83% vs. 38% at 3 years, P < 0·0001) and OS rates (88% vs. 61% at 5 years; P = 0·003). This study demonstrates that quantitative PCR is a robust, accurate and feasible technique for implementing in the daily routine as a surrogate for GEP‐arrays.
Lattice-Simplex Coverings and the 84-Shape

It is known that diameters of abelian Cayley graphs with n generators are related to Manhattan diameters of a particular type of lattice tile called a Cayley tile and that determining the lower bound of those diameters is related to the density of lattice-simplex coverings of Rn. We construct a natural tile associated with each lattice-simplex covering and show that the 84-shape (discovered in [R. Dougherty and V. Faber, The Degree-Diameter Problem for Several Varieties of Cayley Graphs, http://www.c3.lanl.gov/dm/pub/laces.html (1994) and C. M. Fiduccia, J. S. Zito, and E. Mann, Network Interconnection Architectures and Translational Tilings, Tech. report, Center for Computing Science, Bowie, MD, 1994]) represents a local mininum of the density of lattice coverings of R3 by a particular simplex D (the convex hull of the unit basis vectors).
Enhanced excretion of vitamin D binding protein in type 1 diabetes: a role in vitamin D deficiency?

CONTEXT Vitamin D deficiency is an increasingly recognized comorbidity in patients with both type 1 (T1D) and type 2 diabetes, particularly associated with the presence of diabetic nephropathy. OBJECTIVE Because we have previously reported enhanced excretion of megalin in the urine of T1D patients with microalbuminuria, we hypothesized that concurrent urinary loss of the megalin ligand, vitamin D binding protein, might contribute mechanistically to vitamin D deficiency. DESIGN AND PARTICIPANTS Examining a study cohort of 115 subjects with T1D, aged 14-40 yr, along with 55 age-matched healthy control subjects, we measured plasma and urine concentrations of vitamin D binding protein (VDBP) along with serum concentrations of total calcium, parathyroid hormone, 25-hydroxyvitamin D, and 1, 25-dihydroxyvitamin D; these results were compared between groups and investigated for relationships with metabolic control status or with albuminuria. MAIN OUTCOME MEASURE Between-group differences in urinary VDBP concentration were the main outcome measures. RESULTS A marked increase in the urinary excretion of VDBP was apparent in subjects with T1D, compared with control subjects. Using multivariate regression modeling, significant correlates of urinary VDBP excretion included microalbuminuria (P = 0.004), glycosylated hemoglobin (P = 0.010), continuous glucose monitoring system average capillary glucose (P = 0.047), and serum 1,25(OH)(2)D concentrations (P = 0.037). Vitamin D deficiency or insufficiency was slightly more prevalent in diabetic subjects with albuminuria, coincident with the increase in urine VDBP excretion. CONCLUSIONS These findings suggest that, theoretically, exaggerated urinary loss of VDBP in T1D, particularly in persons with albuminuria, could contribute mechanistically to vitamin D deficiency in this disease.
Serum FSH and testicular morphology in male infertility

OBJECTIVE In patients with azoospermia serum FSH helps to differentiate between obstruction or spermatogenetic dysfunction as the possible cause of this condition. The role of FSH in the diagnosis of infertile men with oligoasthenoteratozoospermia is less clearly defined. In order to evaluate the diagnostic significance of serum FSH in the management of male infertility, serum FSH levels were related to testicular morphology from bilateral biopsies of infertile men.
Paracoccidioidomicose: estudo radiológico e pulmonar de 58 casos

Provas funcionais respiratorias foram realizadas em 58 pacientes com Paracoccidioidomicose (Pbmicose) pulmonar uni e multifocal em 52; tumoral em 5 e genital feminino interno em 01. A idade oscilou de 20 a 74 anos e a duracao da doenca variou de 3 a 25 anos. Manifestacoes respiratorias, tegumentares e linfaticas foram predominantes. Catorze deles desenvolveram Cor pulmonale, funcao renal alterada em 19, modificacoes eletrocardiograficas em 8 e atividade hiporeatora adrenal em 13 dos 20 casos estudados. A analise radiologica revelou lesoes designadas: leve em 16; moderada em 24 e grave em 18 que a evolucao evidenciaram: manutencao e piora, respectivamente, em 35 e em 23 deles. As provas funcionais respiratorias mostraram: espirografia normal em 17; obstrutivo em 32 e misto em 9 doentes. O espaco morto foi superior a 35% em 25 e a ventilacao alveolar minuto estava elevada em 54. A diferenca alveolo-arterial de Oxigenio estava aumentada em todos. A analise estatistica revelou associacao significativa entre radiologia: evolucao radiologica e a funcao pulmonar. A Pbmicose em doentes tabagistas inveterados conduziu ao enfisema, enquanto que as modificacoes alveolo-arteriais anoxemicas propiciaram a disseminacao da Doenca de Lutz.
Loss of the C terminus of melanocortin receptor 2 (MC2R) results in impaired cell surface expression and ACTH insensitivity.

OBJECTIVE Mutations in melanocortin receptor 2 (MC2R) and its related melanocortin receptor accessory protein (MRAP) cause familial glucocorticoid deficiency. We identified a novel MC2R mutation, K289fs. This unique mutation in the C terminus of MC2R is located in the intracellular part of the protein for which the exact function is unknown. SETTING A 6-wk-old boy presented with severe hypoglycemia, unmeasurable cortisol, and grossly elevated ACTH but normal electrolytes. Genetic analysis revealed homozygote K289fs mutation in MC2R. His parents and siblings were heterozygous but phenotypically normal. INTERVENTION AND RESULTS The role of the C terminus of MC2R was studied in two cell systems. Because the K289fs mutant changes the last eight amino acids of the protein and leads to protein elongation, wild-type MC2R and C-terminally mutated constructs were tested for activity to respond to ACTH in an OS3 cell-based reporter assay. Wild-type and alanine-substituted constructs responded normally to ACTH. By contrast K289fs and M290X had a total loss of activity. Cell surface assays and confocal localization studies revealed that K289fs and M290X receptors were not found at the cell surface, indicating that their transport from the endoplasmic reticulum to the cell membrane is disrupted. Interestingly, coimmunoprecipitation experiments showed no alteration in the interaction of mutant MC2R with MRAP, suggesting that interaction between these two proteins does not guarantee normal localization. CONCLUSIONS Loss of the C terminus of MC2R impairs cell surface expression and ACTH sensitivity but does not disrupt interaction of MC2R with MRAP. These findings highlight the extreme sensitivity of MC2R to structural disruption.
Continuum of Zero Points of a Mapping on a Compact, Convex Set

Let X be a nonempty, compact and convex set in Rn and $\phi$ be an outer semicontinuous mapping from X to the collection of nonempty, compact convex subsets of Rn. We show that for any nonzero vector c in Rn there exists a set of stationary points of $\phi$ on X with respect to c connecting a point in the boundary of X at which $c^{\top} x$ is minimized on X to another point in the boundary of X at which $c^{\top}x$ is maximized on X. We provide several conditions on $\phi$ under which there exists a continuum of zero points of $\phi$ connecting two such points in the boundary of X, and an intersection result on a convex, compact set. An application to constrained equilibria is also given.
Validation and reliability of a disease‐specific quality of life measure (the TranQol) in adults and children with thalassaemia major

This study aimed to demonstrate the validity, reliability and responsiveness of a new disease‐specific quality of life (QoL) questionnaire for children and adults with thalassaemia major, the Transfusion‐dependent QoL questionnaire (TranQol). 106 participants (51 adults and 55 children) were recruited from six North American thalassaemia treatment centres with a mean age of 20·7 years (standard deviation [SD] 9, range 7–51 years). The mean total TranQol score was 71 (SD 17, 32–97) on a scale of 0–100. Patients with co‐morbidities had significantly lower scores (63 vs. 75, P = 0·001). TranQol scores showed substantial agreement (P < 0·001) with the Health Utilities Index Mark 3 (all patients, r = 0·65), the Pediatric QoL (children, r = 0·77) and the Short Form (36) physical (adults, r = 0·69) and mental summary scores (r = 0·76). In the subgroup who rated their QoL as better, there was a 4·0 point (SD 9·0) improvement in TranQol scores, from baseline of 67·1–71·1 one week later (P = 0·008). Test–retest reliability was excellent (intra‐class correlation coefficient, 0·93). The TranQol was valid, with acceptable correlation for all administered measures and was reliable and responsive to change. The TranQol can be incorporated into future studies of thalassaemia major.
Haematopoietic stem cell transplantation for severe sickle cell disease in childhood: a single centre experience of 50 patients

Despite improvements in medical management, sickle cell disease (SCD) remains associated with severe morbidity and decreased survival. Allogeneic haematopoietic stem cell transplantation (HSCT) remains the only curative approach. We report the outcome of 50 consecutive children with severe SCD that received HSCT in our unit between November 1988 and April 2013. The stem cell source was bone marrow (n = 39), cord blood (n = 3), bone marrow and cord blood (n = 7) and peripheral blood stem cells (n = 1). All patients had ≥1 severe manifestation: 37 presented with recurrent vaso‐occlusive crises/acute chest syndrome, 27 cerebral vasculopathy and 1 nephropathy. The conditioning regimen consisted of busulfan + cyclophosphamide (BuCy) before November 1991 and BuCy + rabbit antithymocyte globulin after that date. Since 1995, all patients have been treated with hydroxycarbamide (HC) prior to transplantation for a median duration of 2·7 years. Median age at transplantation and median follow‐up was 8·3 and 7·7 years, respectively. Acute graft‐versus‐host disease (GVHD) and chronic GVHD were observed in 11 and 10 patients, respectively. An excellent outcome was achieved, with 8‐year overall survival and event‐free survival (EFS) rates of 94·1% and 85·6%, respectively. Since HC introduction, no graft failure occurred and EFS reached 97·4%. Prior treatment with HC may have contributed to successful engraftment.
Clinical Course of Acute Maxillary Sinusitis Documented by Sequential MRI Scanning

A prospective study was designed to assess clinical and mucosal changes that occur during resolution of acute maxillary sinusitis. Thirteen previously healthy subjects with symptoms of acute sinusitis and radiographic opacification of at least one maxillary sinus were entered into the study and treated with amoxicillin/clavulinate potassium. Assessment of clinical symptoms, clinical examination, and magnetic resonance imaging (MRI) of the maxillary sinuses were performed at baseline and at days 3, 7, 10, 14, 21, 28 and 56 after initiation of therapy. The T2 values from the MRI scans were analyzed to approximate the more viscous and more fluid-like components of the maxillary sinus contents. After three days of antibiotic therapy, there was marked improvement in facial tenderness, thickness of nasal discharge, volume of nasal discharge, headache, and nasal congestion. Ten to 14 days of treatment were required, however, for improvement in nasal patency. MRI analysis of the volume percentage of air in the involved sinuses showed that by 10 days, only half of the opacification (fluid and thickened mucosa) had resolved. By 56 days, the sinuses were only about 80% aerated. This improvement was attributed mainly to resolution of the more fluid-like component. This study shows that: (1) tissue/fluid changes in sinusitis can be followed with MRI, and (2) although treatment of acute maxillary sinusitis generally results in clinical resolution of symptoms within one week, mucosal changes can persist for 8 weeks or more.
Osteonecrosis of the jaw and renal safety in patients with newly diagnosed multiple myeloma: Medical Research Council Myeloma IX Study results

Bisphosphonates are recommended in patients with osteolytic lesions secondary to multiple myeloma. We report on the safety of bisphosphonate therapy with long‐term follow‐up in the Medical Research Council Myeloma IX study. Patients with newly diagnosed multiple myeloma were randomised to zoledronic acid (ZOL; 4 mg intravenously every 21–28 d) or clodronate (CLO; 1600 mg/d orally) plus chemotherapy. Among 1960 patients (5·9‐year median follow‐up), both bisphosphonates were well tolerated. Acute renal failure events were similar between groups (ZOL 5·2% vs. CLO 5·8% at 2 years; incidence plateaued thereafter). The overall incidence of confirmed osteonecrosis of the jaw (ONJ) was low, but higher with ZOL (ZOL 3·7% vs. CLO 0·5%; P < 0·0001). ONJ events were generally low grade and most occurred between 8 and 30 months (median time to ONJ, 23·7 months). Among 10 patients with ONJ recovery data, four patients in the ZOL group completely recovered, two patients improved, and three patients experienced no improvement; one CLO patient experienced no improvement. Dental surgery or trauma preceded ONJ in six ZOL patients. The incidence of renal adverse events was similar for ZOL and CLO. ONJ incidence remained low and was lower with CLO compared to ZOL. We have seen no further ONJ cases to date.
Long‐term follow‐up and second malignancies in 487 patients with hairy cell leukaemia

A large, multicentre, retrospective survey of patients with hairy cell leukaemia (HCL) was conducted in France to determine the frequency of second malignancies and to analyse the long‐term effects of the established purine nucleoside analogues (PNAs), cladribine and pentostatin. The survey retrospectively reviewed the medical history of patients and their immediate family, clinical and biological presentation at the time of HCL diagnosis, treatment choice, response to treatment, time to relapse and cause of death. Data were collected for 487 patients with HCL. Of the patients included in the survey, 18% (88/487) had a familial history of cancers, 8% (41/487) presented with malignancies before HCL diagnosis and 10% (48/487) developed second malignancies after HCL was diagnosed. An excess incidence of second malignancies was observed, with a standardized incidence ratio (SIR) of 1·86 (95% confidence interval (CI): 1·34–2·51), with no significant difference between PNAs. For second haematological malignancies alone, the SIR was markedly increased at 5·32 (95% CI: 2·90–8·92). This study highlights the high frequency of cancers in HCL patients and their family members. The frequency of second malignancies is notably increased, particularly for haematological malignancies. The respective role of pentostatin and cladribine in the development of second malignancies is debatable.