Unpolarized transverse momentum distributions from a global fit of Drell-Yan and semi-inclusive deep-inelastic scattering data

We present an extraction of unpolarized transverse-momentum-dependent parton distribution and fragmentation functions based on more than two thousand data points from several experiments for two different processes: semi-inclusive deep-inelastic scattering and Drell-Yan production. The baseline analysis is performed using the Monte Carlo replica method and resumming large logarithms at (NLL)-L-3 accuracy. The resulting description of the data is very good (chi(2)/N-dat = 1.06). For semi-inclusive deep-inelastic scattering, predictions for multiplicities are normalized by factors that cure the discrepancy with data introduced by higher-order perturbative corrections

May osteoarticular infections be influenced by vitamin D status? An observational study on selected patients

BACKGROUND: Vitamin D deficiency has been associated with a high number of health outcomes, and its role on the immune system has been deeply investigated in recent years, although poor data are still available on vitamin D status in orthopedic infections including those of prosthetic implants. METHODS: We focused on preoperative values of 25(OH)D in selected groups of patients with septic (Group A) or aseptic (Group B) prosthetic loosening, infective bone disease such as septic arthritis and osteomyelitis (Group C) and other orthopedic pathologies (Group D) to evaluate differences in the vitamin D status. RESULTS: A high prevalence of vitamin D deficiency was recorded among the study population (16.5\u2009\ub1\u20095.4 ng/mL, mean\u2009\ub1\u2009SD). Interestingly, all patients with an infection presented a higher 25(OH)D concentration (17.7\u2009\ub1\u20095.3 ng/mL) in respect to uninfected ones (15.1\u2009\ub1\u20095.6 ng/mL). Significantly higher levels of 25(OH)D were observed in patients with prosthetic joint infection (18.5\u2009\ub1\u20096.5 ng/mL), when compared with those presenting an aseptic loosening (13.6\u2009\ub1\u20099.4 ng/mL). CONCLUSIONS: Deficiency in vitamin D levels have been found in orthopaedic patients. Prosthetic joint infections seems to be associated to higher values of vitamin D in respect to other bone infections or to other orthopaedic conditions requiring surgery. More studies are needed to improve the knowledge on vitamin D status in these patients and to better clarify the role of vitamin D in relation to osteoarticular infections

Immune Checkpoint Inhibitors in Advanced Prostate Cancer: Current Data and Future Perspectives

In the last 10 years, many new therapeutic options have been approved in advanced prostate cancer (PCa) patients, granting a more prolonged survival in patients with metastatic disease, which, nevertheless, remains incurable. The emphasis on immune checkpoint inhibitors (ICIs) has led to many trials in this setting, with disappointing results until now. Therefore, we discuss the immunobiology of PCa, presenting ongoing trials and the available clinical data, to understand if immunotherapy could represent a valid option in this disease, and which subset of patients may be more likely to benefit. Current evidence suggests that the tumor microenvironment needs a qualitative rather than quantitative evaluation, along with the genomic determinants of prostate tumor cells. The prognostic or predictive value of immunotherapy biomarkers, such as PD-L1, TMB, or dMMR/MSI-high, needs further evaluation in PCa. Monotherapy with immune checkpoint inhibitors (ICIs) has been modestly effective. In contrast, combined strategies with other standard treatments (hormonal agents, chemotherapy, PARP inhibitors, radium-223, and TKIs) have shown some results. Immunotherapy should be better investigated in biomarker-selected patients, particularly with specific pathway aberrations (e.g., AR-V7 variant, HRD, CDK12 inactivated tumors, MSI-high tumors). Lastly, we present new possible targets in PCa that could potentially modulate the tumor microenvironment and improve antitumor activity with ICIs

Application of the Meet-URO score to metastatic renal cell carcinoma patients treated with second- and third-line cabozantinib

Background: The addition of neutrophil-to-lymphocyte ratio (NLR) and bone metastases to the International Metastatic RCC Database Consortium (IMDC) score (by the Meet-URO score) has been shown to better stratify pretreated metastatic renal cell carcinoma (mRCC) patients receiving nivolumab. This study aimed to validate the Meet-URO score in patients receiving cabozantinib to assess its predictivity and prognostic role. Methods: A multicenter retrospective analysis evaluated mRCC patients receiving ⩾second-line cabozantinib. NLR, IMDC score and bone metastases were assessed before the start of cabozantinib. The primary endpoint was overall survival (OS). Harrell’s c-index was calculated to compare the accuracy of the prediction of the two scores. Results: Overall, 174 mRCC patients received cabozantinib as second and third line (51.7% and 48.3%, respectively) with a median follow-up of 6.8 months. A shorter median overall survival (mOS) was observed for the IMDC poor-risk group, NLR ⩾3.2 and the presence of bone metastases, while the IMDC intermediate-risk group had a similar mOS to the favourable-risk one. Applying the Meet-URO score, three risk groups were identified: group 1 (55.2% of patients) with a score of 0–3, group 2 (38.5%) with a score of 4–8 and group 3 (6.3%) with a score of 9. Compared to group 1 (mOS: 39.4 months), a statistically significant worse mOS was observed in group 2 (11.2 months) and group 3 (3.2 months) patients, respectively. The Meet-URO c-index score was 0.640, showing a higher discriminative ability than the IMDC score (c-index: 0.568). Conclusion: This analysis showed that the Meet-URO score provides a more accurate prognostic stratification than the IMDC score in mRCC patients treated with ⩾second-line cabozantinib besides nivolumab. Moreover, it is an easy-to-use tool with no additional costs for clinical practice (web-calculator is available at: https://proviso.shinyapps.io/Meet-URO15_score/). Future investigations will include the application of the Meet-URO score to the first-line immunotherapy-based combination therapies

Leaching behaviour of pendimethalin causes toxicity towards different cultivars of Brassica juncea and Brassica campestris in sandy loam soil

An experiment was conducted at the farm of Zonal Adaptive Research Station, Uttar Banga Krishi Viswavidhyalaya, Pundibari, Cooch Behar, West Bengal to evaluate the effect of pendimethalin on the yield, weed density and phytotoxicity in different varieties of rai (Brassica juncea) and yellow sarson (B. campestris var. yellow sarson) under higher soil moisture regime in Terai region of West Bengal. Pre-emergence application of pendimethalin at higher dose i.e. 1.0 kg/ha recorded higher plant mortality (30.92%) due to the presence of higher concentration of pendimethalin residue (0.292 µg/g) till the tenth day of crop age and consequently had the reduced yield (12.59 q/ha) than the dose of 0.7 kg/ha (13.33 q/ha) where plant mortality was only 12.62% due to comparatively lower level of pendimethalin residue (0.192 µg/g). Although the application of pendimethalin at the rate of 1.0 kg/ha was able to control weed more efficiently (18.96/m2) than the dose of 0.7 kg/ha (30.41/m2) and subsequent lower doses. The herbicide leached down to the root zone resulting in phytotoxicity towards crop. Yellow sarson group (Brassica campestris) showed more susceptibility than rai (Brassica juncea) group against pendimethalin application at higher doses

Cross-resistance to elvitegravir and dolutegravir in 502 patients failing on raltegravir: a French national study of raltegravir-experienced HIV-1-infected patients

OBJECTIVES: The objectives of this study were to determine the prevalence and patterns of resistance to integrase strand transfer inhibitors (INSTIs) in patients experiencing virological failure on raltegravir-based ART and the impact on susceptibility to INSTIs (raltegravir, elvitegravir and dolutegravir). PATIENTS AND METHODS: Data were collected from 502 treatment-experienced patients failing a raltegravir-containing regimen in a multicentre study. Reverse transcriptase, protease and integrase were sequenced at failure for each patient. INSTI resistance-associated mutations investigated were those included in the last ANRS genotypic algorithm (v23). RESULTS: Among the 502 patients, at failure, median baseline HIV-1 RNA (viral load) was 2.9 log10 copies/mL. Patients had been previously exposed to a median of five NRTIs, one NNRTI and three PIs. Seventy-one percent harboured HIV-1 subtype B and the most frequent non-B subtype was CRF02_AG (13.3%). The most frequent mutations observed were N155H/S (19.1%), Q148G/H/K/R (15.4%) and Y143C/G/H/R/S (6.7%). At failure, viruses were considered as fully susceptible to all INSTIs in 61.0% of cases, whilst 38.6% were considered as resistant to raltegravir, 34.9% to elvitegravir and 13.9% to dolutegravir. In the case of resistance to raltegravir, viruses were considered as susceptible to elvitegravir in 11% and to dolutegravir in 64% of cases. High HIV-1 viral load at failure (P < 0.001) and low genotypic sensitivity score of the associated treatment with raltegravir (P < 0.001) were associated with the presence of raltegravir-associated mutations at failure. Q148 mutations were selected more frequently in B subtypes versus non-B subtypes (P = 0.004). CONCLUSIONS: This study shows that a high proportion of viruses remain susceptible to dolutegravir in the case of failure on a raltegravir-containing regimen