Miracle-dz/UniFAR-FTUs huggingface dataset:
The role of the B cell receptor V region in peripheral B cell survival

We investigate the role of the antigen‐specific B cell receptor (BCR) in the establishment and maintenance of the peripheral B cell pools. We studied the fate of a population of transgenic B cells expressing a BCR without V region (TgΔVμ). We found that the TgΔVμ B cells can populate the peripheral B cell pools in the absence of other B cells, but when in the presence of a second population of non‐transgenic B cells, they are virtually absent from the mature B cell compartments. By studying the rate of accumulation of 5‐bromo‐2′‐deoxyuridine we show that the peripheral TgΔVμ B cells have a shorter life‐span compared to non‐transgenic B cells. By directly comparing the fate of two populations of transgenic B cells, either lacking or expressing a V region, we were able to assign the poorest competitive ability and the short peripheral survival of the TgΔVμ B cells to the lack of an antigen‐binding site. The results obtained support the involvement of the V region in the persistence of peripheral B cell populations.
Cytokines and their interactions with other inflammatory mediators in the pathogenesis of sepsis and septic shock

Sepsis and its potentially lethal complication, septic shock, belong to the most frequent causes of mortality in modern clinics and, especially, in intensive care units. Moreover, the incidence of this condition is steadily increasing. Multiple circumstances underlie this increasing trend: increasing longevity in developed countries with attendant susceptibility to infections; increased use of immunosuppressive therapy, e.g. for patients with organ transplants; and increased u-e of extensive and sophisticated surgery that allows survival for patients who would otherwise die of causes such as cancer, extensive trauma, burns, extensive blood loss. etc. The pathogenesis of shock has been a matter of intensive study for many years. The vascular and tissue alterations in shock have of old been recognized to be mainly due to the pharmacological actions of plasmaand tissue-derived mediators. Amongst these mediators, the so-called cytokines have recently received increasing attention of investigators. Not only have ‘older’ members of this molecular family (e.g. the endogenous pyrogens) been fully characterized, but new members have also been discovered. Moreover, the complex of interactions amongst cytokines, the socalled cytokine network, is now being progressively disentangled. Here we wish to review current views on the role of the cytokine network in sepsis. Before doing so, it may be useful to recall that the potentially lethal complications of sepsis always comprise three elements (Fig. 1). Any one of these may act
Hampering Immune Suppressors: Therapeutic Targeting of Myeloid-Derived Suppressor Cells in Cancer

Abstract Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells with suppressive properties that preferentially expand in cancer. Myeloid-derived suppressor cells mainly suppress T-cell proliferation and cytotoxicity, inhibit natural killer cell activation, and induce the differentiation and expansion of regulatory T cells. The wide spectrum of MDSC suppressive activity in cancer and its role in tumor progression have rendered these cells a promising target for effective cancer immunotherapy. In this review we briefly discuss the origin of MDSCs and their main mechanisms of suppression and focus more on the approaches developed up to date targeting of MDSCs in tumor-bearing animals and cancer patients.
Glyphosate rodent carcinogenicity bioassay expert panel review

Abstract Glyphosate has been rigorously and extensively tested for carcinogenicity by administration to mice (five studies) and to rats (nine studies). Most authorities have concluded that the evidence does not indicate a cancer risk to humans. The International Agency for Research on Cancer (IARC), however, evaluated some of the available data and concluded that glyphosate probably is carcinogenic to humans. The expert panel convened by Intertek assessed the findings used by IARC, as well as the full body of evidence and found the following: (1) the renal neoplastic effects in males of one mouse study are not associated with glyphosate exposure, because they lack statistical significance, strength, consistency, specificity, lack a dose-response pattern, plausibility, and coherence; (2) the strength of association of liver hemangiosarcomas in a different mouse study is absent, lacking consistency, and a dose-response effect and having in high dose males only a significant incidence increase which is within the historical control range; (3) pancreatic islet-cell adenomas (non-significant incidence increase), in two studies of male SD rats did not progress to carcinomas and lacked a dose-response pattern (the highest incidence is in the low dose followed by the high dose); (4) in one of two studies, a non-significant positive trend in the incidence of hepatocellular adenomas in male rats did not lead to progression to carcinomas; (5) in one of two studies, the non-significant positive trend in the incidence of thyroid C-cell adenomas in female rats was not present and there was no progression of adenomas to carcinomas at the end of the study. Application of criteria for causality considerations to the above mentioned tumor types and given the overall weight-of-evidence (WoE), the expert panel concluded that glyphosate is not a carcinogen in laboratory animals.
More on risk/benefit ratio of anti‐IL‐2 receptor monoclonal antibodies

Acute rejection arises when alloreactive T-cells infiltrate the graft. A critical step in the activation of these cells is the expression of the high affinity interleukin-2 receptor, which induces rapid proliferation of T-cells when interleukin-2 binds to it. The IL2-R consists of three transmembrane protein chains: a (CD25), b (CD122), and c (CD132). CD25 does not transduce a signal, but associates with CD122 and CD132 to form the receptor that triggers signaling [1]. Clinically efficient anti-IL2-R are directed at the a chain and disturbs the IL-2 high affinity site. A first human trial with a murine anti-IL2-R named 33B3.1, initiated in the middle 1980s, suggested the efficacy of monoclonal antibodies against IL-2 high affinity receptor in decreasing acute rejection episodes as well as a good clinical tolerance [2]. In a first randomized comparison of a nonmodified antibody with polyclonal antithymocyte globulin (ATG) induction, the use of this murine anti-IL2-R was followed by a similar incidence of acute rejections with 70% of patients being rejection-free within the first year post-transplant [3]. The benefit of anti-IL2-R induction was ultimately demonstrated in a large pivot study using a chimeric antibody [4]. The same results were subsequently confirmed in prospective randomized studies including high-risk recipients of renal retransplant [5] and simultaneous pancreas–kidney transplant [6]. These agents represent, with ATG, one of the most popular induction strategies used after renal transplantation. Lim et al. in this issue retrospectively analyzed from the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA), the long-term (i.e. 5 years) benefits of anti-interleukin-2 receptor monoclonal antibody (antiIL-2R) induction after all types of renal transplantation. From 2000 to 2006, 1470 patients received IL2-R induction and 1874 patients did not. Maintenance immunosuppression included calcineurin inhibitors (CNI), mycoplenolate mofetil, azathioprine, rapamycin, and steroids. The use of anti-IL2-R was associated with significantly less acute rejection episodes (although the incidence was 20%), improved graft function at 5 years (but not of graft survival) and a similar risk of adverse events, including malignancy-induced death [7]. In the absence of randomized studies focused on longterm end-points such as chronic rejection, malignancies, graft survival, patient survival etc. the balance between efficacy, safety, and cost is difficult to ascertain. Only retrospective analyses of large cohorts from national or international registries are able to identify predictive factors with potential direct effects on these crucial longterm endpoints. The term induction was introduced in the 1960s when ATG was initially given from the day of Correspondence Jean-Paul Soulillou MD, Departments of Nephrology and Clinical Immunology, Transplantation, ITUN, Nantes University Hospital, Nantes, France. Tel. : 33 240 08 74 10; fax: 33 240 08 74 11; e-mail: jean-paul. soulillou@univ-nantes.fr
Life-threatening exacerbation of Kaposi's sarcoma after prednisone treatment for immune reconstitution inflammatory syndrome.

The recovery of immune functions after the initiation of HAART has been associated with clinical deterioration despite control of immunological and virological parameters, a condition that is now termed ‘immune reconstitution inflammatory syndrome’ (IRIS) [1]. The most common IRIS-associated diseases are mycobacterial, cytomegalovirus, and herpes-associated conditions, including Kaposi’s sarcoma (KS) [1–3]. IRIS conditions associated with mycobacterial infections [4], retinal cytomegalovirus [5], cryptoccocal meningitis [6], and herpes zoster [7], have been treated with primary anti-infective therapy, the continuation of HAART and anti-inflammatory therapy, usually steroids, with varying degrees of success.
Identification of Novel Mutations in the LRR-Cap Domain of C21orf2 in Japanese Patients With Retinitis Pigmentosa and Cone-Rod Dystrophy.

PURPOSE C21orf2 encodes a ciliary protein related to syndromic and nonsyndromic retinal degeneration. The purpose of this study was to identify novel mutations of C21orf2 associated with syndromic autosomal recessive retinitis pigmentosa (arRP) and autosomal recessive cone-rod dystrophy (arCRD) by using whole exome sequencing of a Japanese cohort. METHODS Whole exome sequencing was performed on DNA from affected and healthy members from 147 families with retinal degenerations. Identified nonsense and missense mutations were further restricted by using the reported single nucleotide variation frequencies and inherited patterns. The effect of the mutations was examined by in vitro assays. RESULTS Novel mutations in C21orf2 were found in Japanese patients with arRP with skeletal defects or arCRD. Compound heterozygous mutations, from one family (p.V111M and p.Y107H), and a homozygous mutation, from another family (p.Y107C), were all located in the leucine-rich repeat C-terminal domain required for protein stabilization. C21orf2 was expressed in the retina through the developing to the mature stage, and the protein localized to the photoreceptor cilia in the adult retina. In vitro expression showed reduced levels and affected localizations of mutated protein products compared to the wild type. CONCLUSIONS The identified C21orf2 mutations decreased protein stability and affected cytoplasmic localization of C21orf2. Since C21orf2 was required for ciliogenesis, our data suggested that reduced levels of functional C21orf2 induced photoreceptor degradation through abnormal cilia formation, leading to arRP or arCRD in the retina.
A Novel Probabilistic Model for Link Unification Grammar

Since the early 90s, there has been a rising interest in applying probabilistic models in syntactic parsing, and significant progress has been achieved. The most influential work include, among others, research using probabilistic lexicalized context free grammars in the form of production rules (or similarly, tree-adjoining grammars and its derivatives), probabilistic dependency grammars; and probabilistic constraints-based grammars [Lafferty, J., Sleator, D. , and Temperley, D. , 1992; Magerman, D. , 1995; Collins, M, 1997; Eisner, J., 1997; Chelba and Jelinek, 1997; Ratnaparkhi, A. , 1999; Charniak, E. , 2000]. Based on the discussion of different methods, we propose a new bottom-up link unification parsing algorithm in the link grammar framework together with a novel probabilistic model. In addition, we also try to provide some intuitive justification for the assumptions made in the probabilistic model. Initial results in terms of bracket recall and precision on the Penn TreeBank close-test set have reached beyond 91%, which shows that our proposed probabilistic model is leading to an encouraging direction.
B Cell-Derived IL-10 Does Not Regulate Spontaneous Systemic Autoimmunity in MRL.Faslpr Mice

B cells contribute to the pathogenesis of chronic autoimmune disorders, like systemic lupus erythematosus (SLE), via multiple effector functions. However, B cells are also implicated in regulating SLE and other autoimmune syndromes via release of IL-10. B cells secreting IL-10 were termed “Bregs” and were proposed as a separate subset of cells, a concept that remains controversial. The balance between pro- and anti-inflammatory effects could determine the success of B cell-targeted therapies for autoimmune disorders; therefore, it is pivotal to understand the significance of B cell-secreted IL-10 in spontaneous autoimmunity. By lineage-specific deletion of Il10 from B cells, we demonstrated that B cell-derived IL-10 is ineffective in suppressing the spontaneous activation of self-reactive B and T cells during lupus. Correspondingly, severity of organ disease and survival rates in mice harboring Il10-deficient B cells are unaltered. Genetic marking of cells that transcribe Il10 illustrated that the pool of IL-10–competent cells is dominated by CD4 T cells and macrophages. IL-10–competent cells of the B lineage are rare in vivo and, among them, short-lived plasmablasts have the highest frequency, suggesting an activation-driven, rather than lineage-driven, phenotype. Putative Breg phenotypic subsets, such as CD1dhiCD5+ and CD21hiCD23hi B cells, are not enriched in Il10 transcription. These genetic studies demonstrated that, in a spontaneous model of murine lupus, IL-10–dependent B cell regulation does not restrain disease and, thus, the pathogenic effects of B cells are not detectably counterbalanced by their IL-10–dependent regulatory functions.
A prospective 5-year study of fixed partial prostheses supported by implants with machined and TiO2-blasted surface.

PURPOSE The aim of the present study was to evaluate whether there was a difference between machined and TiO(2)-blasted implants regarding survival rate and marginal bone loss during a 5-year observation period. MATERIALS AND METHODS A total of 133 implants (Astra Tech Dental Implants; Astra Tech AB, Mölndal, Sweden) were placed in 50 patients at 6 centers in 4 Scandinavian countries. Forty-eight implants were installed in the maxilla and 85 implants in the mandible. A randomization and a stratification were done, so that each fixed partial prosthesis was supported by at least 1 machined and 1 TiO(2)-blasted implant. The implant-supported fixed partial prostheses (ISFPP) were fabricated within 2 months after postoperative healing. A total of 52 ISFPP (17 maxillary, 35 mandibular) were inserted. The patients were clinically examined once a year for 5 years. At the annual follow-up, biological as well as technical complications were recorded. RESULTS Of the 133 implants placed, 3 were reported as failed after 5 years of follow-up, resulting in an overall cumulative survival rate of 97.6%. The cumulative implant survival rates were 100% for the TiO(2)-blasted implants and 95.1% for the machined implants. No significant difference in survival was, however, found between the machined and TiO(2)-blasted implants after 5 years. The mean marginal bone loss in the maxilla was 0.21 +/- 0.83 mm (SD) for the machined implants and 0.51 +/- 1.11 mm (SD) for the TiO(2)-blasted implants during the 5-year observation period. In the mandible, the mean marginal loss was 0.22 +/- 1.13 mm for the machined implants and 0.52 +/- 1.07 mm for the TiO(2)-blasted implants from baseline to the 5-year examination. No significant difference in marginal bone loss between the 2 surface groups was found during the 5-year observation period. CONCLUSIONS The present study shows good 5-year results with small ISFPP in the mandible, as well as in the maxilla. No significant differences were found in failure rate and marginal bone loss around implants with a machined rather than a TiO(2)-blasted surface. J Prosthodont 2001;10:2-7.
Risperidone in the treatment of first episode psychosis.

OBJECTIVE To evaluate the efficacy and safety of risperidone in Singapore patients with first-episode psychosis in an eight-week open label prospective study. METHOD Previously untreated male and female patients aged 18 - 65 with DSM IV schizophreniform disorder or DSM IV schizophrenia for no longer than 12 months were recruited from Woodbridge Hospital and Geylang Psychiatric Outpatient Clinic. Patients were treated with risperidone for 56 days. Outcome was assessed with the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression scale (CGI). Safety was assessed by monitoring of vital signs and by comparing the frequency of adverse events (AEs) before and after treatment. RESULTS 24 patients with a mean age of 33.29+/-9.12 years and a mean duration of illness of 166.5+/-111.4 days (median 180 days) were included. The mean risperidone dosage was 2.7 mg +/- 1.0 at day 56. Mean PANSS total scores reduced by 50.21% from 88.29+/-21.55 at baseline to 43.96+/-7.5 at endpoint (p < 0.001). The responder rate (> or = 20% reduction in the total PANSS score) was 87.5%. 13 patients (54.2%) exhibited a 50% or greater reduction in total PANSS score. Except for item G5 (mannerisms and posturing) all single PANSS items were reduced significantly. The CGI scores of all patients improved at endpoint. No serious adverse events were reported. CONCLUSIONS Overall the therapy of first-episode psychosis patients with risperidone was effective and safe.
Quadriceps strength and the time course of functional recovery after total knee arthroplasty.

STUDY DESIGN Prospective study with repeated measures. OBJECTIVES The overall goal of this investigation was to describe the time course of recovery of impairments and function after total knee arthroplasty (TKA), as well as to provide direction for rehabilitation efforts. We hypothesized that quadriceps strength would be more strongly correlated with functional performance than knee flexion range of motion (ROM) or pain at all time periods studied before and after TKA. BACKGROUND TKA is a very common surgery, but very little is known regarding the influence of impairments on functional limitations in this population. METHODS AND MEASURES Forty subjects who underwent unilateral TKA followed by rehabilitation, including 6 weeks of outpatient physical therapy, were studied. Testing occurred at 5 time periods: preoperatively, and at 1, 2, 3, and 6 months after surgery. Test measures included quadriceps strength, knee ROM, timed up-and-go test, timed stair-climbing test, bodily pain, and general health and knee function questionnaires. RESULTS Subjects experienced significant worsening of knee ROM, quadriceps strength, and performance on functional tests 1 month after surgery. Quadriceps strength went through the greatest decline of all the physical measures assessed and never matched the strength of the uninvolved limb. All measures underwent significant improvements following the 1-month test. Quadriceps strength was the most highly correlated measure associated with functional performance at all testing sessions. CONCLUSIONS Functional measures underwent an expected decline early after TKA, but recovery was more rapid than anticipated and long-term outcomes were better than previously reported in the literature. The high correlation between quadriceps strength and functional performance suggests that improved postoperative quadriceps strengthening could be important to enhance the potential benefits of TKA.
Technology, Group Process, and Group Outcomes: Testing the Connections in Computer-Mediated and Face-to-Face Groups

This article examines the effect of communication media on group processes and the consequent effect of processes on group cohesiveness, satisfaction, and productivity using mediated regression analysis. Data are based on Straus and McGrath (1994), in which 72 three-person groups worked on idea generation, intellective, and judgment tasks in either computer-mediated (CM) or face-to-face (FTF) discussions. Straus and McGrath found that in comparison to FTF groups, CM groups were less productive across tasks and expressed lower satisfaction in the judgment task. This article adds to findings about group outcomes by showing that CM groups expressed lower cohesiveness than did FTF groups. Analysis of communication processes shows that CM groups had higher proportions of task communication and disagreement and greater equality of participation. In contrast to prior reports that people using electronic communication are depersonalized, CM groups did not engage in more attacking behavior and they exchanged higher rates of supportive communication than did FTF groups. Mediated regression analysis reveals that the group process accounted for the effect of communication mode on cohesiveness and satisfaction but not on productivity. Results suggest that media effects on outcomes, as well as on processes such as task focus and equality of participation, are due to the rates by which CM and FTF groups operate and not necessarily because of any inherently depersonalizing feature of electronic communication.
PELVIC EPENDYMOMA ARISING FROM THE SMALL BOWEL

Summary A 37‐year‐old woman underwent resection of an abdominal tumour which was adherent to the wall of the ileum. The diagnosis of an ependymoma was supported by evidence of typical perivascular pseudorosettes which stained positive for glial fibrillary acidic protein and contained abundant intermediate filaments within the elongated processes by electron microscopy. Flow cytometric study showed a diploid population of tumour cells. This is the first case of an ependymoma arising from the small bowel without any connection to the genital tract, the omentum or with the sacroccygeal area. As is the case with other unusual and ectopic localisations of ependymomas, prognosis of this tumour is difficult to evaluate.
Wrinkly skin syndrome: Phenotype and additional manifestations

The wrinkly skin syndrome is an autosomal recessive disorder characterized by wrinkling of the skin of the dorsum of the hands and feet, decreased elastic recoil of the skin, an increased number of palmar and plantar creases, multiple musculoskeletal abnormalities, microcephaly, and mental retardation. Our patient is characteristic of the syndrome as previously described, and confirms the presence of mental retardation and microcephaly as component manifestations, with the additional findings of connective tissue abnormalities evidenced by an atrial septal aneurysm.
Amplification of chromosomal segment 4q12 in non-small cell lung cancer

In cancer, proto-oncogenes are often altered by genomic amplification. Here we report recurrent focal amplifications of chromosomal segment 4q12 overlapping the proto-oncogenes PDGFRA and KIT in non-small cell lung cancer (NSCLC). Single nucleotide polymorphism (SNP) array and fluorescent in situ hybridization (FISH) analysis indicate that 4q12 is amplified in 3-7% of lung adenocarcinomas and 8-10% of lung squamous cell carcinomas. In addition, we demonstrate that the NSCLC cell line NCI-H1703 exhibits focal amplification of PDGFRA and is dependent on PDGFRα activity for cell growth. Treatment of NCI-H1703 cells with PDGFRA-specific shRNAs or with the PDGFRα/KIT small molecule inhibitors imatinib or sunitinib leads to cell growth inhibition. However, these observations do not extend to NSCLC cell lines with lower-amplitude and broader gains of chromosome 4q. Together these observations implicate PDGFRA and KIT as potential oncogenes in NSCLC, but further study is needed to define the specific characteristics of those tumors that could respond to PDGFRα/KIT inhibitors.