Miracle-dz/UniFAR-FTUs huggingface dataset:
Neurological Manifestations in Systemic Lupus Erythematosus: A Single Centre Study from North East India.

INTRODUCTION Neurological manifestations although common in Systemic Lupus Erythematosus (SLE), are often not recognized due to their diversed and varied presentation. Therefore, the study was planned to highlight the pattern of neurological involvement in SLE to help in early recognition. AIM To study the pattern of neurological involvement in SLE and its correlation with disease activity and different investigation. MATERIALS AND METHODS This hospital based prospective observational study was carried out from August 2009 to July 2010. Diagnosed cases of SLE [based upon American Rheumatism Association (ARA) criteria] who presented with neurological manifestations at the time of diagnosis or develop during the course of the disease were included in the study. They were assessed clinically and investigated with neuroimaging and neurophysiological tests as applicable. RESULTS In total, 52 consecutive patients with SLE were evaluated, 92% were female. The most common age group was 21 to 25 years. Nervous system involvement was found in 19 (36.54%) patients. Cognitive impairment was the most frequent manifestation, present in 11 (57.89%) patients followed by seizure disorder in eight patients (42.1%). Peripheral neuropathy was diagnosed in eight (42.1%), acute confusional state in six (31.57%) and headache and depression was diagnosed in five (26.31%) patients each. Less common manifestations were psychosis, movement disorder and aseptic meningitis. Percentage of neurological manifestations directly correlated with disease activity. A significant difference was found in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score between the patients with Neuro Psychiatric Systemic Lupus Erythematosus (NPSLE) and those without NPSLE (32.42±16.34 Vs 17.3±10.6). CONCLUSION Neurological involvement in SLE is seen relatively early in the course of the disease with cognitive impairment being the most common manifestation and correlate with disease activity.
Expression of smoothened protein in colon cancer and its prognostic value for postoperative liver metastasis.

UNLABELLED BACKGROUDS: The hedgehog (Hh) signaling pathway is composed of patched (PTCH) and smoothened (SMO), two transmembrane proteins, and downstream glioma-associated oncogene homolog (Gli) transcription factors. Hh signaling plays a pathological role in the occurrence and development of various cancers. METHODS To investigate the expression of SMO protein in colon cancer and its association with clinicopathological parameters and postoperative liver metastasis, immunohistochemistry was performed with paraffin-embedded specimens of 96 cases. Relationships between SMO protein expression and clinicopathological parameters, postoperative liver metastasis were analyzed. RESULTS IHC examination showed that SMO protein expression was significantly increased in colon cancer tissues compared to normal colon tissues (P = 0.042), positively related to lymph node metastases (P = 0.018) and higher T stages (P = 0.026). Postoperative live metastasis-free survival was significantly longer in the low SMO expression group than in those with high SMO expression (48.7 ± 8.02 months vs 28.0 ± 6.86 months, P=0.036). Multivariate analysis showed SMO expression level to be an independent prognostic factor for postoperative live metastasis-free survival (95% confidence interval [CI] =1.46-2.82, P = 0.008). CONCLUSIONS Our results suggest that in patients with colon cancer, the SMO expression level is an independent biomarker for postoperative liver metastasis, and SMO might play an important role in colon cancer progression.
How well do parental and peer relationships in adolescence predict health in adulthood?

Aim: Although health effects of social relationships are well-researched, long-term health consequences of adolescent family as well as peer relationships are poorly understood. The aim of the study was to explore the prospective importance of parental and peer social relationships in adolescence on internalising and functional somatic symptoms in adulthood. Methods: Data were drawn from four waves of the Northern Swedish Cohort Study, response rate 94.3%, N=1001. Outcome variables were internalising and functional somatic symptoms at the ages of 21, 30 and 42. Relationship variables at age 16 were poor parental contact and three indicators of poor peer relationships. Associations were assessed in multivariate ordinal logistic regressions with adjustment for confounders and baseline health. Results: Results show that the main relationships-related predictors of adult internalising symptoms were self-rated poor peer relationships in terms of spending time alone during after-school hours and poor parental relationship. Functional somatic symptoms on the other hand were most strongly associated with poor parental contact and not being happy with classmates at age 16. Conclusions: The quality of parental and peer relationships in adolescence predicts adult mental and functional somatic health as much as 26 years later, even when accounting for confounders and adolescent symptomatology. This study extends past research by exploring how both adolescent parental and peer relationships (self-reported as well as teacher reported) predict adult self-reported health.
Evidence for a role of the 5-HT1B receptor and its adaptor protein, p11, in l-DOPA treatment of an animal model of Parkinsonism

Parkinson's disease (PD) is characterized by a progressive degeneration of substantia nigra dopaminergic neurons projecting to the striatum. Restoration of dopamine transmission by l-DOPA relieves symptoms of PD but causes prominent side effects. There is a strong serotonin innervation of the striatum by serotonergic neurons that remains relatively preserved in PD. The study of this innervation has been largely neglected. Here, we demonstrate that chronic l-DOPA administration to 6-OHDA-lesioned rodents increases, via D1 receptors, the levels of the 5-HT1B receptor and its adaptor protein, p11, in dopamine-denervated striatonigral neurons. Using unilaterally 6-OHDA-lesioned p11 WT and KO mice, it was found that administration of a selective 5-HT1B receptor agonist, CP94253, inhibited l-DOPA-induced rotational behavior and abnormal involuntary movements in a p11-dependent manner. These data reveal an l-DOPA-induced negative-feedback mechanism, whereby the serotonin system may influence the symptomatology of Parkinsonism.
New β‐lactam–β‐lactamase inhibitor combinations in clinical development

Tazobactam was the most recent β‐lactamase inhibitor to be approved in 1993. Since the approval of piperacillin–tazobactam, the complexity of β‐lactamase–mediated resistance among Gram‐negative bacilli has increased enormously. After more than 20 years since the first such combination, amoxicillin–clavulanic acid, was approved, several new β‐lactam–β‐lactamase inhibitor combinations have reached late‐stage (phase II and beyond) clinical trials. These include ceftolozane–tazobactam (2:1, ratios of β‐lactam to β‐lactamase inhibitor in parentheses), ceftazidime–avibactam (4:1), ceftaroline–avibactam (1:1), and imipenem–cilastatin–MK‐7655 (2:2:1 and 4:4:1). Avibactam and MK‐7655 are diazabicyclooctane (DABCO) inhibitors and thus not β‐lactams themselves; they include class A carbapenemases and class C enzymes within their spectra of activity. Ceftolozane is an antipseudomonal cephalosporin, and tazobactam is used to protect it against extended spectrum β‐lactamases to which it is labile. Additional novel combinations are in preclinical development. This review will focus on the biochemistry, antimicrobial activity, pharmacodynamics, and clinical development of these novel combinations.
Isolation and measurement of pancreatic amylase in human serum and urine.

We describe a sensitive quantitative procedure for separating isoamylases in human serum, urine, and tissue homogenates. Two components have been discerned with chromatographic characteristics resembling those of pancreatic and salivary amylases, respectively. Several lines of evidence—derived from studies in normal subjects, pancreatectomized patients, and patients with acute pancreatitis—indicate that the pancreas is probably the source of the component in serum and urine that exhibits characteristics of pancreatic amylase. The source of the component resembling salivary amylase has not yet been fully defined. Isoamylase analysis of extracts of fallopian tube and liver revealed two amylase components with chromatographic properties similar to pancreatic and salivary amylases, respectively.
Expression of Cdx2 and Claudin-2 in the Multistage Tissue of Gastric Carcinogenesis

In this paper, we investigated Cdx2 and claudin-2 expression in pathological paraffin tissues of sinus ventriculi from gastroscopic biopsy to determine the correlation between the expressions of these 2 genes during gastric carcinogenesis by immunochemical ABC technique. Altogether, we analyzed 108 chronic superficial gastritis, 55 chronic atrophic gastritis, 109 intestinal-type metaplasia, 93 dysplasia and 52 gastric intestinal-type adenocarcinoma samples. Our results indicated that the percentage of Cdx2-positive cases was 0% (0/108) for chronic superficial gastritis, 0% (0/55) for chronic atrophic gastritis, 90.83% (99/109) for intestinal-type metaplasia, 51.61% (48/93) for dysplasia and 61.54% (32/52) for gastric intestinal-type adenocarcinoma, primarily expressed in the cell nucleus and partly in the cytoplasm (p < 0.05); interestingly, the percentage for the intestine-type metaplasia was markedly high. The percentage of claudin-2-positive cases was 0% (0/108) for chronic superficial gastritis, 0% (0/55) for chronic atrophic gastritis, 0% (0/109) for intestinal-type metaplasia, 35.48% (33/93) for dysplasia and 71.15% (37/52) for gastric intestinal-type adenocarcinoma, primarily in the cell membrane and gradually increased in the multistage process of gastric carcinogenesis (p < 0.05). Significant correlations were found between claudin-2 and Cdx2 protein expression in dysplasia and intestine-type adenocarcinoma (r = 0.112, p < 0.05). Thus, there may be a correlation between the expression of claudin-2 and Cdx2 in stages of dysplasia and cancer.
Modeling, Analysis and Performance Comparison of Two Direct Sampling DCSK Receivers under Frequency Nonselective Fading Channels

Two direct sampling correlator-type receivers for differential chaos shift keying (DCSK) communication systems under frequency nonselective fading channels are proposed. These receivers operate based on the same hardware platform with different architectures. In the ﬁrst scheme, namely Sum-Delay-Sum (SDS) receiver, the sum of all samples in a chip period is correlated with its delayed version. The correlation value obtained in each bit period is then compared with a ﬁxed threshold to decide the binary value of recovered bit at the output. On the other hand, the second scheme, namely Delay-Sum-Sum (DSS) receiver, calculates the correlation value of all samples with its delayed version in a chip period. The sum of correlation values in each bit period is then compared with the threshold to recover the data. The conventional DCSK transmitter, frequency nonselective Rayleigh fading channel, and two proposed receivers are mathematically modeled in discrete-time domain. We evaluated the BER performance of the receivers by means of both theoretical analysis and numerical simulation. The performance comparison shows that the two proposed receivers can perform well under the studied channel, where the performances get better when the number of paths increases and the DSS receiver outperforms the SDS one.
Évaluation génétique et génomique de nouveaux caractères en bovins laitiers

La mise en place de la selection genomique rend possible l’inclusion de nouveaux caracteres dans les objectifs de selection, en profitant des marges offertes par l’augmentation du progres genetique sur les caracteres historiques. En parallele, les attentes des eleveurs, de la societe et des filieres orientent la selection genetique vers des objectifs plus larges et complexes. Deux groupes de nouveaux caracteres ont ete analyses dans le cadre de l’amelioration genetique des bovins laitiers : les caracteres de carcasse des jeunes bovins de races mixtes et les caracteres de resistance aux lesions podales en race Holstein, afin de preparer la mise en place d’une selection genetique et genomique de ces caracteres. Pour ces deux caracteres, les modeles d’evaluation polygenique les plus pertinents ont ete developpes et les parametres genetiques correspondant ont ete estimes. Ces derniers revelent que la selection genetique des caracteres de carcasse des jeunes bovins sera relativement aisee, alors que celle de la resistance aux lesions podales sera plus difficile, mais possible, du fait de l’existence d’une variabilite genetique. Ils mettent egalement en evidence qu’un progres genetique sur les caracteres de carcasse des jeunes bovins n’est pas genetiquement oppose a un progres genetique sur la production laitiere. Ils mettent enfin en evidence deux groupes de lesions podales genetiquement distinctes. Par ailleurs, plusieurs strategies pour prendre en compte la nonexhaustivite des donnees de lesions podales ont ete testees. Plusieurs approches d’evaluation ont ete comparees. Pour les deux groupes de caracteres, l’approche dite « Single-Step Genomic BLUP » s’est revelee la plus prometteuse, meme si les autres approches genomiques « en deux etapes », donnaient des resultats aux caracteristiques relativement proches. Ces etudes ont mene a la mise en place d’evaluations genetiques et genomiques en routine pour les deux groupes de caracteres, pour lesquelles les methodes d’evaluation classiques ont ete retenues par souci de coherence avec les evaluations actuelles, tout en demontrant l’interet d’une evolution vers l’approche en une etape a moyen terme. Les principales questions soulevees et les grandes etapes identifiees lors des etudes de ces deux caracteres ont ete rassemblees au sein d’une ebauche de methodologie pour le developpement d’evaluations genetiques pour de nouveaux caracteres.
Hemodynamic Maladjustment and Disease Progression in Nephrosis with FSGS

Idiopathic nephrotic syndrome (NS) associated with focal segmental glomerulosclerosis (FSGS) and severe renal function impairment is usually refractory to the conventional treatment and progresses to end‐stage renal disease. Herein, we reported 10 patients with NS‐FSGS who had initially had CCr 34 ± 12 mL/min/1.73m2 (normal 120 mL/min/1.73m2), FE Mg 7.8 ± 2.6% (normal 2.2%), 24‐h urinary protein 3.1 g (normal < 200 mg) and been followed up for over 10 years. The initial intrarenal hemodynamic study revealed a marked elevation of efferent arteriolar resistance (RE 17289 ± 8636 dyne.s.cm− 5; normal 3000 dyne.s.cm− 5), intraglomerular hypertension (PG 57 ± 1 mm Hg; normal 52 mm Hg), hyperfiltration (FF 0.24; normal 0.2), marked reductions in GFR 35 ± 17 mL/min/1.73m2, renal plasma flow (RPF 159 ± 61 mL/min/1.73m2; normal 600 mL/min/1.73m2) and peritubular capillary flow (PTCF 123 ± 57 mL/min/1.73m2; normal 480 mL/min/1.73m2). Such a hemodynamic alteration indicated a hemodynamic maladjustment with a preferential constriction at RE. Treatment consists of multidrugs, namely angiotensin converting enzyme inhibitor, calcium channel blocker, antiplatelet and anticoagulant, with or without angiotensin II receptor antagonist. Following the treatment, correction of hemodynamic maladjustment has been achieved which is characterized by reductions in RE 6046 ± 2191 dyne.s. cm− 5, PG 52 ± mm Hg, FF 0.19 ± 0.1 and increments in RPF 341 ± 118 mL/min/1.73m2, PTCF 280 ± 106 mL/min/1.73m2 and GFR 64 ± 17 mL/min/1.73m2. Coinciding with hemodynamic improvement, there has been a steadily increased creatinine clearance and improvement in FE Mg 4.3 ± 2.6% and suppression of proteinuria 0.29 ± 0.4g/24 h after the period of follow‐up of greater than 10 years.
Depression among Alzheimer's caregivers: Identifying risk factors

Purpose: The purpose of this study was to reveal risk factors contributing to the development of depression among caregivers of Alzheimer's disease patients. Methods: In a cross-sectional study, all caregivers of consecutive Alzheimer's disease patients were asked to participate in the study. Patient and caregiver depression was evaluated by using the Yesavage Geriatric Depression Scale (GDS). Information regarding patients' functional status, driving status, and type of behavioral abnormalities was obtained from caregivers. Patients' functional status was evaluated by using the Katz Activity of Daily Living (ADL) scale. The Folstein Mini-Mental Status Examination (MMSE) was used to evaluate cognition. Risk factors for Alzheimer's caregiver depression were assessed by means of logistic regression analysis. Results: A total of 92 patients and caregivers were evaluated. Fifteen were excluded due to incomplete data. A total of 77 pairs were included in this analysis. The age of caregivers ranged from 28 to 88 years. Mean (standard deviation [SD]) age was 63.1 (SD = 16.3) years old. Husbands and wives (caregivers) accounted for 49.4 percent; daughters or sons (or daughters-or sons-in-law) accounted for 42.9 percent. There were 29 caregivers (38 percent) found to be depressed. By using multivariate analysis, the following factors have been identified as risk factors for depression in Alzheimer's caregivers: depression in the dementia patient; ADL functional scores of 12 or greater; and the presence of hallucinations. Conclusion: Three risk factors were found to have a strong association with Alzheimer's caregiver depression. Early recognition of such risk factors may help to identify Alzheimer's caregivers with depression.
Changes in the Uptake of GABA and Taurine During Neuronal and Glial Maturation

Abstract: The influence of the time of culture on GABA and taurine uptake was investigated in spontaneously matured cultures of glial and neuronal origins and in cultures treated with cyclic nucleotides. In the spontaneously matured cultures the capacity of the high‐affinity neuronal GABA transport system increased with time in culture. Essentially opposite results were found for the uptake of GABA by glial cultures. In contrast with the neuronal uptake of GABA, the capacity of the taurine transport system was significantly decreased. Uptake of taurine into glia, however, exhibited a progressive increase with the period of culture. The values of Km, for the high‐affinity systems were always found to range around 10 μM. It is suggested that, in mature cells, neuronal uptake sites are of prime importance for GABA transport, while taurine uptake may be more specifically directed towards glial cells. When cultures were treated with cyclic nucleotide derivatives, a morphological differentiation was induced, which could not be linked to a stimulation of GABA or taurine uptake systems as compared with the non‐treated cultures.
Biological response modifiers for the treatment of Crohn’s disease

Although standard medical therapy in Crohn’s disease is efficient in most patients, a substantial proportion of patients suffering from chronic active disease do not adequately respond to standard therapy. In these patients, alternative regimens have to be considered. Due to the major advances in understanding the pathogenesis of this complex disease involving genetic, environmental, microbial and immunological factors, various new biological therapies targeting key mechanisms have emerged. In this review, a critical appraisal of modern therapeutical concepts will be presented, focusing on antibody and small inhibitory molecule therapies, including inhibition of TNF-α and other pro-inflammatory cytokines, adhesion molecules and T cell activation, as well as hormonal therapies.
Spleen serves as a reservoir of osteoclast precursors through vitamin D-induced IL-34 expression in osteopetrotic op/op mice

Osteoclasts are generated from monocyte/macrophage-lineage precursors in response to colony-stimulating factor 1 (CSF-1) and receptor activator of nuclear factor-κB ligand (RANKL). CSF-1–mutated CSF-1op/op mice as well as RANKL−/− mice exhibit osteopetrosis (OP) caused by osteoclast deficiency. We previously identified RANKL receptor (RANK)/CSF-1 receptor (CSF-1R) double-positive cells as osteoclast precursors (OCPs), which existed in bone in RANKL−/− mice. Here we show that OCPs do not exist in bone but in spleen in CSF-1op/op mice, and spleen acts as their reservoir. IL-34, a newly discovered CSF-1R ligand, was highly expressed in vascular endothelial cells in spleen in CSF-1op/op mice. Vascular endothelial cells in bone also expressed IL-34, but its expression level was much lower than in spleen, suggesting a role of IL-34 in the splenic generation of OCPs. Splenectomy (SPX) blocked CSF-1–induced osteoclastogenesis in CSF-1op/op mice. Osteoclasts appeared in aged CSF-1op/op mice with up-regulation of IL-34 expression in spleen and bone. Splenectomy blocked the age-associated appearance of osteoclasts. The injection of 2-methylene-19-nor-(20S)-1α,25(OH)2D3 (2MD), a potent analog of 1α,25-dihidroxyvitamin D3, into CSF-1op/op mice induced both hypercalcemia and osteoclastogenesis. Administration of 2MD enhanced IL-34 expression not only in spleen but also in bone through a vitamin D receptor-mediated mechanism. Either splenectomy or siRNA-mediated knockdown of IL-34 suppressed 2MD-induced osteoclastogenesis. These results suggest that IL-34 plays a pivotal role in maintaining the splenic reservoir of OCPs, which are transferred to bone in response to diverse stimuli, in CSF-1op/op mice. The present study also suggests that the IL-34 gene in vascular endothelial cells is a unique target of vitamin D.
Low-Dose Oral Cyclophosphamide and Methotrexate Maintenance for Hormone Receptor-Negative Early Breast Cancer: International Breast Cancer Study Group Trial 22-00.

PURPOSE To evaluate the benefit of low-dose cyclophosphamide and methotrexate (CM) maintenance, which previously demonstrated antitumor activity and few adverse effects in advanced breast cancer, in early breast cancer. PATIENTS AND METHODS International Breast Cancer Study Group (IBCSG) Trial 22-00, a randomized phase III clinical trial, enrolled 1,086 women (1,081 intent-to-treat) from November 2000 to December 2012. Women with estrogen receptor- and progesterone receptor-negative (< 10% positive cells by immunohistochemistry) early breast cancer any nodal and human epidermal growth factor receptor 2 status, were randomly assigned anytime between primary surgery and 56 days after the first day of last course of adjuvant chemotherapy to CM maintenance (cyclophosphamide 50 mg/day orally continuously and methotrexate 2.5 mg twice/day orally on days 1 and 2 of every week for 1 year) or to no CM. The primary end point was disease-free survival (DFS), which included invasive recurrences, second (breast and nonbreast) malignancies, and deaths. RESULTS After a median of 6.9 years of follow-up, DFS was not significantly better for patients assigned to CM maintenance compared with patients assigned to no CM, both overall (hazard ratio [HR], 0.84; 95% CI, 0.66 to 1.06;P = .14) and in triple-negative (TN) disease (n = 814; HR, 0.80; 95% CI, 0.60 to 1.06). Patients with TN, node-positive disease had a nonstatistically significant reduced HR (n = 340; HR, 0.72; 95% CI, 0.49 to 1.05). Seventy-one (13%) of 542 patients assigned to CM maintenance did not start CM. Of 473 patients who received at least one CM maintenance dose (including two patients assigned to no CM), 64 (14%) experienced a grade 3 or 4 treatment-related adverse event; elevated serum transaminases was the most frequently reported (7%), followed by leukopenia (2%). CONCLUSION CM maintenance did not produce a significant reduction in DFS events in hormone receptor-negative early breast cancer. The trend toward benefit observed in the TN, node-positive subgroup supports additional exploration of this strategy in the TN, higher-risk population.