FGFR4 Arg388 allele correlates with tumour thickness and FGFR4 protein expression with survival of melanoma patients

A single nucleotide polymorphism in the gene for FGFR4 (−Arg388) has been associated with progression in various types of human cancer. Although fibroblast growth factors (FGFs) belong to the most important growth factors in melanoma, expression of FGF receptor subtype 4 has not been investigated yet. In this study, the protein expression of this receptor was analysed in 137 melanoma tissues of different progression stages by immunohistochemistry. FGFR4 protein was expressed in 45% of the specimens and correlated with pTNM tumour stages (UICC, P=0.023 and AJCC, P=0.046), presence of microulceration (P=0.009), tumour vascularity (P=0.001), metastases (P=0.025), number of primary tumours (P=0.022), overall survival (P=0.047) and disease-free survival (P=0.024). Furthermore, FGFR4 Arg388 polymorphism was analysed in 185 melanoma patients by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The Arg388 allele was detected in 45% of the melanoma patients and was significantly associated with tumour thickness (by Clark's level of invasion (P=0.004) and by Breslow in mm (P=0.02)) and the tumour subtype nodular melanoma (P=0.002). However, there was no correlation of the FGFR4 Arg388 allele with overall and disease-free survival. In conclusion, the Arg388 genotype and the protein expression of FGFR4 may be potential markers for progression of melanoma

Analysis of Clinical Phenotypes through Machine Learning of First-Line H. pylori Treatment in Europe during the Period 2013–2022: Data from the European Registry on H. pylori Management (Hp-EuReg)

The segmentation of patients into homogeneous groups could help to improve eradication therapy effectiveness. Our aim was to determine the most important treatment strategies used in Europe, to evaluate first-line treatment effectiveness according to year and country. Data collection: All first-line empirical treatments registered at AEGREDCap in the European Registry on Helicobacter pylori management (Hp-EuReg) from June 2013 to November 2022. A Boruta method determined the “most important” variables related to treatment effectiveness. Data clustering was performed through multi-correspondence analysis of the resulting six most important variables for every year in the 2013–2022 period. Based on 35,852 patients, the average overall treatment effectiveness increased from 87% in 2013 to 93% in 2022. The lowest effectiveness (80%) was obtained in 2016 in cluster #3 encompassing Slovenia, Lithuania, Latvia, and Russia, treated with 7-day triple therapy with amoxicillin–clarithromycin (92% of cases). The highest effectiveness (95%) was achieved in 2022, mostly in Spain (81%), with the bismuth–quadruple therapy, including the single-capsule (64%) and the concomitant treatment with clarithromycin–amoxicillin–metronidazole/tinidazole (34%) with 10 (69%) and 14 (32%) days. Cluster analysis allowed for the identification of patients in homogeneous treatment groups assessing the effectiveness of different first-line treatments depending on therapy scheme, adherence, country, and prescription year

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

Actions and impediments for technical debt prevention: Results from a global family of industrial surveys

Background: Preventing the occurrence of technical debt (TD) in software projects can be cheaper than its payment. Prevention practices also help in catching inexperienced developers' 'not-so-good' solutions. However, little is known on how to prevent the occurrence of TD. Aims: To investigate, from the point of view of software practitioners, preventive actions that can be used to curb the occurrence of TD and the impediments that hamper the use of those actions. Method: We use data from the InsighTD Project, a family of industrial surveys specifically designed to study software engineering TD. We use a corpus of answers from 207 practitioners across different geographic locations to identify and analyze - both quantitatively and qualitatively - the TD preventive actions most used in practice. Results: We found that project planning, adoption of good practices, well-defined requirements, creating tests, and training are the most cited preventive actions that curb TD in software projects. We also identified seven preventive action categories and defined relationships among them and TD types. On the other hand, the main impediments to prevent TD are related to inappropriate project planning and lack of expertise of the team. Conclusions: Our list of preventive actions and impediments can help practitioners to implement policies for the sector and guide TD researches in a problem-driven way

On the relationship between technical debt management and process models

As technical debt (TD) potentially occurs as a result of poor decisions that affect software development tasks, one might expect that practitioners following different process models, such as agile, hybrid or traditional, will perceive and manage the effects of TD differently. This study investigates the potential relationship between development process models and TD effects and their management by surveying 432 practitioners from software organizations in Brazil, Chile, Colombia, and the United States. Results indicate that, although opinions about debt prevention and repayment are the same regardless of the process model, there are differences in how practitioners monitor and feel the effects of TD. Development teams can use our findings to have a clearer view of the possible effects and managerial influence of TD in their projects for each type of process model

Fatores relacionados à presença de anticorpos IgG anti-Toxoplasma gondii em caprinos leiteiros do Estado da Bahia.

A toxoplasmose constitui-se uma das principais causas de abortos e natimortos em caprinos leiteiros. O desenvolvimento da caprinocultura leiteira no Estado da Bahia, com o manejo intensivo e semi-intensivo têm permitido a propagação de vários coccídeos, incluindo o Toxoplasma gondii. A presença deste protozoário foi determinada em nove rebanhos, para tanto, utilizaram-se 373 caprinos de diferentes raças, categorias zootécnicas e idades. Do total de animais avaliados, 61 (16,35%) apresentaram reações positivas para anticorpos IgG anti-T.gondii (ponte de corte de 1:16), segundo a técnica de imunofluorescência indireta. Em todos os rebanhos foram encontrados animais positivos, com uma amplitude de variação entre 2 e 35% com títulos de 1:16 (13,1%), 1:32 (16,4%), 1:64 (16,4%), 1:128 (27,8%), 1:256 (11,5%) e > de 1:256 (14,8%). Considerando a categoria zootécnica, as fêmeas em lactação obtiveram o maior percentual de positividade (22,8%) seguida de fêmeas gestantes (20,8%), fêmeas secas (17%) e fêmeas jovens (11,1%). Com relação às raças estudadas, a Parda Alpina apresentou maior freqüência de positivos (18,8%), seguida da raça Saanen (16,8%) e Anglo Nubiana (4,8%). A faixa etária que apresentou maior número de reações positivas foi a de quatro a seis anos (26,67%). Os resultados analisados indicaram uma ampla distribuição deste coccídeo nos rebanhos caprinos leiteiros