bluuebunny/crossref_metadata_2025_split huggingface dataset:
Completed suicide rates of older adults in 5‐year age bands in Turkey between 2002 and 2013: A retrospective study
Authors: Altınöz Ali E , Yenilmez Çınar , Öner Setenay KD , Yıldız Pınar 
Published: December 2018

AimStudies have shown that the causes and methods of suicides differ among young and old individuals; consequently, it is important to identify the subgroups that are at high risk for suicide to aid in suicide prevention. The present study compared the causes and methods of suicides between 2002 and 2013 among older adults aged 65–69 years, 70–74 years and ≥75 years by completed crude suicide rate and sex.MethodsData detailing sex, the causes and methods of completed suicides in older adults aged 65–69 years, 70–74 years and ≥75 years that occurred between 2002 and 2013 were drawn from the Turkish Statistical Institute.ResultsIn all age groups, crude suicide rates were threefold more frequent among men than among women. In both sexes, the most frequent suicide cause was mental illness. In the group aged 65–69 years, the most common cause of suicide was financial difficulty for men and marital conflict for women. The most frequent suicide method among older adults of both sexes was hanging. In all age groups, firearms use was more common among men and jumping from a high place was more common among women.ConclusionThe present findings suggest that the most common suicide cause in both sexes and in all age groups was mental illness in Turkey. To prevent suicidal behavior in older adults,; it is important to diagnose mental disorders, such as mood disorders and substance abuse, and to treat them quickly. Geriatr Gerontol Int 2019; 19: 66–69.
Optimisation of Lithium Chromatography for Isotopic Analysis in Geological Reference Materials by MC‐ICP‐MS
Authors: Li Wenshuai , Liu Xiao‐Ming , Godfrey Linda V. 
Published: December 2018

The lithium isotope system can be an important tracer for various geological processes, especially tracing continental weathering. The key to this application is the accurate and precise determination of lithium isotopic composition. However, some of the previously established column separation methods are not well behaved when applied to chemically diverse materials, due to the significant variations in matrix/lithium ratios in some materials. Here, we report a new dual‐column system for lithium purification to achieve accurate and precise analysis of lithium isotopic compositions using a multi‐collector inductively coupled plasma‐mass spectrometer (MC‐ICP‐MS). Compared with single‐column systems, our dual‐column system yielded a consistent elution range of the lithium‐bearing fraction (7–16 ml) for samples with a large range of lithium loads and matrix compositions, so that column re‐calibration is not required. In addition, this method achieved complete lithium recovery and low matrix interference (e.g., Na/Li ≤ 1) with a short elution time (~ 6 h, excluding evaporation), with the entire procedure completed in 1.5 days. We report high precision Li isotopic compositions in twelve chemically diverse materials including seawater, silicates, carbonates, manganese nodules and clays. New recommended Li isotopic values and associated uncertainties are presented as reference values for quality control and inter‐laboratory calibration for future research and were consistent with previously published data. However, significant lithium isotopic variances (~ 1‰) in BHVO‐2 from different batches suggest Li isotopic heterogeneity in this reference material and that Li isotopic studies using this reference material should be treated with caution.
Defining clinically significant prostate cancer on the basis of pathological findings
Authors: Matoso Andres , Epstein Jonathan I 
Published: December 2018

The definition of clinically significant prostate cancer is a dynamic process that was initiated many decades ago, when there was already evidence that a great proportion of patients with prostate cancer diagnosed at autopsy never had any clinical symptoms. Autopsy studies led to examinations of radical prostatectomy (RP) specimens and the establishment of the definition of significant cancer at RP: tumour volume of 0.5 cm3, Gleason grade 6 [Grade Group (GrG) 1], and organ‐confined disease. RP studies were then used to develop prediction models for significant cancer by the use of needle biopsies. The first such model was used to delineate the first active surveillance (AS) criteria, known as the ‘Epstein’ criteria, in which patients with a cancer Gleason score of 3 + 3 = 6 (GrG1) involving fewer than two cores, and <50% of any given core, and a prostate‐specific antigen density of <0.15 ng/ml per cm3 had a minimal risk of significant cancer at RP. These were adopted as components of the ‘very‐low‐risk category’ of the National Comprehensive Cancer Network guidelines, in which AS is supported as a management option. With the increase in the popularity of AS, much research has been carried out to better define significant/insignificant cancer, in order to be able to safely offer AS to a larger proportion of patients without the risk of undertreatment. Research has focused on allowing higher volume tumours, focal extraprostatic extension, and a limited amount of Gleason pattern 4, and the significance of different morphological patterns of Gleason 4. Other areas of research that will probably impact on the field but that are not covered in this review include the molecular classification of tumours and imaging techniques.
Grading of prostate cancer: a work in progress
Authors: Kweldam C F , van Leenders G J , van der Kwast T 
Published: December 2018

Grading of prostate cancer has evolved substantially over time, not least because of major changes in diagnostic approach and concomitant shifts from late‐ to early‐stage detection since the adoption of PSA testing from the late 1980s. After the conception of the architecture‐based nine‐tier Gleason grading system more than 50 years ago, several changes were made in order to increase its prognostic impact, to reduce interobserver variation and to improve concordance between prostate needle biopsy and radical prostatectomy grading. This eventually resulted in the current five‐tier grading system, with a much more detailed description of the individual architectural patterns constituting the remaining three Gleason patterns (i.e. grades 3–5). Nevertheless, there is room for improvement. For instance, distinction of common grade 4 subpatterns such as ill‐formed and fused glands from the grade 3 pattern is challenging, blurring the division between low‐risk patients who could be eligible for deferred therapy and those who need curative therapy. The last few years have witnessed the publication of several studies on the prognostic impact of individual architectural subpatterns showing that, in particular, the cribriform pattern exceeded the prognostic impact of other grade 4 subpatterns. This review provides an overview of the changes in prostate cancer grading over time and provides a thorough description of the various Gleason subpatterns, the current evidence of their prognostic impact and areas of contention. Potential practical ways for improvements of the current grading system are also put forward.
A facile route for the preparation of silica foams using rice husk ash
Authors: Hossain SK Saddam , Mathur Lakshya , Bhardwaj Aman , Roy Pradip Kumar 
Published: December 2018

AbstractThis work aims to synthesize silica foam with around 75 vol. % open porosity without using any additive or pore forming agents, in order to prevent the generation of greenhouse gases during pore formation in the silica matrix. Waste rice husk ash (RHA) derived silica is used as a silica source, which is extracted through the alkali extraction synthesis route. Several physical characterizations such as X‐ray diffraction (XRD), scanning electron microscope (SEM), transmission electron microscopy (TEM), differential thermal‐thermogravimetric (DTA‐TGA) and FTIR analysis have been done for RHA extracted silica. Silica foam specimens are fabricated through control compaction pressure and at low foaming temperature. Samples which are fired at 550°C for 30 minutes exhibit both a adequate apparent porosity (AP; ~75.82%) and significant compressive strength (~1.54 MPa). It can also be observed that the porosity and strength values are changed with the variation in compaction pressure and foaming temperature.
Skin lesions in organ transplant recipients: a study of 177 consecutive Brazilian patients
Authors: Oliveira Walmar R. P. , Tirico Maria C. C. P. , Souza Anaisa A. V. , Codarin Felipe R. , Silva Lana L. C. , Festa Neto Cyro 
Published: December 2018

AbstractBackgroundSkin lesions are very common among organ transplant recipients (OTR), particularly infections and tumors, because of the immunosuppressive state these patients are put in.Methods177 OTR were examined. Skin lesions were categorized into neoplastic, infectious, and inflammatory diseases.ResultsThe mean age of OTR was 52 years, the mean age at transplantation was 42.7 years, and kidney was the most common organ transplanted (72%). Skin lesions were found in 147 patients (83%). Cutaneous infections were seen in 106 patients (60%). Warts (30%) had the larger incidence and were associated with azathioprine (P = 0.026), cyclosporine (P = 0.006), and tacrolimus (P = 0.009). Superficial mycoses occurred in 16% of OTR, mostly onychomycosis, which was associated with tacrolimus (P = 0.040). Actinic keratosis (AK) occurred in 31% of patients and cutaneous tumors in 56%. Squamous cell carcinoma (SCC) was the most common tumor type affecting 36% of OTR (n = 64), with invasive SCC predominating over in situ SCC, whereas basal cell carcinoma (BCC) accounted for 17%. Both SCC and BCC were more numerous in patients’ skin type I (P < 0.05). SCC was more frequent (36%) in combined kidney and liver recipients (P = 0.004), and BCC was associated with cyclosporine (P = 0.047). Inflammatory complications (acne, alopecia, hypertrichosis, and gingival overgrowth) were observed in 17.5% of patients.ConclusionsOrgan transplant recipients must be regularly evaluated by dermatologists, who should be alert to the onset of infections and skin (pre)malignant diseases in these patients.
High burden of the metabolic syndrome and its component disorders in South Africans with psoriasis
Authors: Goolam Mahyoodeen Nasrin , Crowther Nigel J. , Snyman Tracy , Pillay Lushen , Tikly Mohammed 
Published: December 2018

AbstractBackgroundPsoriasis is associated with cardiometabolic diseases (CMDs) in Caucasians, but no data is available from sub‐Saharan populations on either CMD prevalence or psoriasis risk factors. Our aim was to investigate the prevalence of CMDs in a predominantly non‐Caucasian cohort of South Africans with psoriasis and to determine the principal risk factors associated with psoriasis.MethodsThis was a cross‐sectional case‐control study of adult psoriasis patients (n = 103) and controls (n = 98), comparing sociodemographic, anthropometric, clinical, and biochemical characteristics. The groups were matched for gender, ethnicity, and body mass index (BMI).ResultsThe prevalence of metabolic syndrome (MetS) (52.4% vs. 33.7%; P = 0.007), type 2 diabetes (T2D) (25.2% vs. 4.1%; P < 0.0001), and hypertension (70.9% vs. 46.6%; P = 0.001) were all higher in the psoriasis group. High‐sensitivity CRP was higher in psoriasis patients than controls (4.70 (2.00, 10.9) vs. 2.00 (1.10, 4.80) ng/ml; P < 0.0005). Multivariable logistic regression analysis showed that severe psoriasis was independently associated with MetS (odds ratio [95% CIs]: 4.42 [1.72, 11.4]; P = 0.002), T2D (11.3 [3.07, 41.3]; P = 0.0002), and hypertension (2.48 [0.97, 6.32]; P = 0.05), whilst for psoriasis the principal risk factors were smoking (3.87 [1.97, 7.63]; P < 0.0001) and hsCRP (1.05 [1.00, 1.10]; P = 0.029), with completion of high school (0.23 [0.11, 0.48]; P < 0.0001) being protective.ConclusionsIn this population, psoriasis is characterized by a high burden of CMDs, particularly in those subjects with severe psoriasis. Inflammation plays a role in the etiology of psoriasis, whilst smoking and poor education further increase disease risk.
Lichen planus‐like keratosis: clinicopathological evaluation of 1366 cases
Authors: Vincek Vladimir 
Published: December 2018

AbstractBackgroundLichen planus‐like keratosis (LPLK) is a frequent skin lesion usually biopsied to rule out basal cell carcinoma (BCC). Because of overlapping histopathological characteristics, LPLK is frequently muddled with lichen planus (LP), lichenoid actinic keratosis (LAK), and lupus erythematosus (LE).ObjectiveTo investigate the clinical and histopathological characteristics of LPLK.MethodsA clinicopathologic review was performed of all LPLK cases (1366) signed in one calendar year in a busy academic practice.ResultsLPLK occurs mostly as a single lesion (97%) with the chest (41.4%) being the most common site. It is almost equally present in women and men (51.5%–48.5%). The most common clinical concern (65%) is basal cell carcinoma. Parakeratosis, red blood extravasation, and presence of dermal eosinophils and plasma cells, usually not seen in lichen planus, are helpful signs to suggest LPLK but are seen only in a minority of cases.ConclusionClinicopathologic correlation is necessary to diagnose lichen planus‐like keratosis, as the most consistent feature is a clinical history of a lesion/neoplastic process rather than an inflammatory process. There are histopathologic features that can help distinguish lichen planus‐like keratosis from lichen planus; however, these features are nonspecific and lacking in almost half of the cases.
The distribution of 4‐hydroxy‐hexenal and 4‐hydroxy‐nonenal in different vegetable oils and their formation from fatty acid methyl esters
Authors: Ma Lukai , Liu Guoqin , Cheng Weiwei , Liu Xinqi 
Published: December 2018

SummaryThe formation of 4‐hydroxy‐hexenal (HHE) and 4‐hydroxy‐nonenal (HNE) in eight vegetable oils was investigated at 180 °C. HHE was only detectable in soybean (SBO), rapeseed (RO) and linseed oils (LO). HNE was measured in all tested oils, but was found mainly in corn (CO), sunflower (SO) and soybean oil (SBO). Oil‐dependent formation of HHE/HNE was remarkably observed. Furthermore, different fatty acid methyl esters in tricaprylin, as model oil systems, were constructed to demonstrate their characteristic contribution to HHE/HNE formation. As expected, HHE and HNE originated from the oxidative degradation of methyl linolenate (MLN) and methyl linoleate (ML) respectively. Whereas low concentrations of MLN (<5.0%) and ML (<1.0%) produced no detectable HHE/HNE. The results suggested MLN/ML could induce both HHE/HNE formation and pro‐oxidation at higher concentrations. Unexpectedly, methyl stearate and methyl oleate slightly promoted HHE/HNE formation, which might be attributed to free radical transfer mechanisms during thermal oxidation.
How the thymus shaped immunology and beyond
Authors: Miller Jacques 
Published: December 2018

AbstractBarely 60 years ago, the thymus was considered to be a vestigial organ with no known function or just a graveyard for dying lymphocytes. Now, the thymus and its cells cover a vast area of immunology, genetics and epigenetics relating to medicine, including inflammation, infection, vaccination, dysbiosis, immunodeficiency, allergy, autoimmunity, transplantation, tissue repair, pregnancy and cancer. New technology and approaches, now becoming available, will lead to a much deeper understanding of many of these conditions. Hence, the thymus and its cells will be occupying researchers and clinicians for decades to come.
Primary immunodeficiencies caused by mutations in actin regulatory proteins
Authors: Janssen Erin , Geha Raif S. 
Published: December 2018

SummaryThe identification of patients with monogenic gene defects have illuminated the function of different proteins in the immune system, including proteins that regulate the actin cytoskeleton. Many of these actin regulatory proteins are exclusively expressed in leukocytes and regulate the formation and branching of actin filaments. Their absence or abnormal function leads to defects in immune cell shape, cellular projections, migration, and signaling. Through the study of patients’ mutations and generation of mouse models that recapitulate the patients’ phenotypes, our laboratory and others have gained a better understanding of the role these proteins play in cell biology and the underlying pathogenesis of immunodeficiencies and immune dysregulatory syndromes.
Zero tolerance! A perspective on monogenic disorders with defective regulatory T cells and IBD‐like disease
Authors: Abdel‐Motal Ussama M. , Al‐Shaibi Ahmad , Elawad Mamoun , Lo Bernice 
Published: December 2018

SummaryRecently, several studies have investigated a number of rare monogenic autoimmune disorders, in which the causative genetic defects were identified and found to affect the development or function of regulatory T cells (Tregs). The studies of these disorders have facilitated a deeper understanding of the mechanisms involved in immune regulation and tolerance. Furthermore, these studies have highlighted the importance of Tregs in maintaining homeostasis at the mucosal interface between the host and microbiome. Here, we offer our perspective on these monogenic autoimmune disorders, highlighting their overlapping clinical features with inflammatory bowel disease.
FAS and RAS related Apoptosis defects: From autoimmunity to leukemia
Authors: Meynier Sonia , Rieux‐Laucat Frédéric 
Published: December 2018

SummaryThe human adaptive immune system recognizes almost all the pathogens that we encounter and all the tumor antigens that may arise during our lifetime. Primary immunodeficiencies affecting lymphocyte development or function therefore lead to severe infections and tumor susceptibility. Furthermore, the fact that autoimmunity is a frequent feature of primary immunodeficiencies reveals a third function of the adaptive immune system: its self‐regulation. Indeed, the generation of a broad repertoire of antigen receptors (via a unique strategy of random somatic rearrangements of gene segments in T cell and B cell receptor loci) inevitably creates receptors with specificity for self‐antigens and thus leads to the presence of autoreactive lymphocytes. There are many different mechanisms for controlling the emergence or action of autoreactive lymphocytes, including clonal deletion in the primary lymphoid organs, receptor editing, anergy, suppression of effector lymphocytes by regulatory lymphocytes, and programmed cell death. Here, we review the genetic defects affecting lymphocyte apoptosis and that are associated with lymphoproliferation and autoimmunity, together with the role of somatic mutations and their potential involvement in more common autoimmune diseases.
What did we learn from CTLA‐4 insufficiency on the human immune system?
Authors: Mitsuiki Noriko , Schwab Charlotte , Grimbacher Bodo 
Published: December 2018

SummaryCytotoxic‐T‐lymphocyte‐antigen‐4 (CTLA‐4) is a negative immune regulator constitutively expressed on regulatory T (Treg) cells and upregulated on activated T cells. CTLA‐4 inhibits T cell activation by various suppressive functions including competition with CD28, regulation of the inhibitory function of Treg cells, such as transendocytosis, and the control of adhesion and motility. Intrinsic CTLA‐4 signaling has been controversially discussed, but so far no distinct signaling pathway has been identified. The CTLA‐4‐mediated Treg suppression plays an important role in the maintenance of peripheral tolerance and the prevention of autoimmune diseases. Human CTLA‐4 insufficiency is caused by heterozygous germline mutations in CTLA4 and characterized by a complex immune dysregulation syndrome. Clinical studies on CTLA4 mutation carriers showed a reduced penetrance and variable expressivity, suggesting modifying factor(s). One hundred and forty‐eight CTLA4 mutation carriers have been reported; patients showed hypogammaglobulinemia, recurrent infectious diseases, various autoimmune diseases, and lymphocytic infiltration into multiple organs. The CTLA‐4 expression level in Treg cells was reduced, while the frequency of Treg cells was increased in CTLA‐4‐insufficient patients. The transendocytosis assay is a specific functional test for the assessment of newly identified CTLA4 gene variants. Immunoglobulin substitution, corticosteroids, immunosuppressive therapy, and targeted therapy such as with CTLA‐4 fusion proteins and mechanistic target of rapamycin (mTOR) inhibitors were applied; patients with life‐threatening, treatment‐resistant symptoms underwent hematopoietic stem cell transplantation. The fact that in humans CTLA‐4 insufficiency causes severe disease taught us that the amount of CTLA‐4 molecules present in/on T cells matters for immune homeostasis. However, whether the pathology‐causing activated T lymphocytes in CTLA‐4‐insufficient patients are antigen‐specific is an unsolved question. CTLA‐4, in addition, has a role in autoimmune diseases and cancer. Anti‐CTLA‐4 drugs are employed as checkpoint inhibitors to target various forms of cancer. Thus, clinical research on human CTLA‐4 insufficiency might provide us a deeper understanding of the mechanism(s) of the CTLA‐4 molecule and immune dysregulation disorders.
Human adenosine deaminase 2 deficiency: A multi‐faceted inborn error of immunity
Authors: Moens Leen , Hershfield Michael , Arts Katrijn , Aksentijevich Ivona , Meyts Isabelle 
Published: December 2018

AbstractHuman adenosine deaminase 1 deficiency was described in the 1970s to cause severe combined immunodeficiency. The residual adenosine deaminase activity in these patients was attributed to adenosine deaminase 2. Human adenosine deaminase type 2 deficiency (DADA2), due to biallelic deleterious mutations in the ADA2 gene, is the first described monogenic type of small‐ and medium‐size vessel vasculitis. The phenotype of DADA2 also includes lymphoproliferation, cytopenia, and variable degrees of immunodeficiency. The physiological role of ADA2 is still enigmatic hence the pathophysiology of the condition is unclear. Preliminary data showed that in the absence of ADA2, macrophage differentiation is skewed to a pro‐inflammatory M1 subset, which is detrimental for endothelial integrity. The inflammatory phenotype responds well to anti‐TNF therapy with etanercept and that is the first‐line treatment for prevention of severe vascular events including strokes. The classic immunosuppressive drugs are not successful in controlling the disease activity. However, hematopoietic stem cell transplantation (HSCT) has been shown to be a definitive cure in DADA2 patients who present with a severe cytopenia. HSCT can also cure the vascular phenotype and is the treatment modality for patients’ refractory to anti‐cytokine therapies. In this review, we describe what is currently known about the molecular mechanisms of DADA2. Further research on the pathophysiology of this multifaceted condition is needed to fine‐tune and steer future therapeutic strategies.