Patients with castration-resistant prostate cancer derive only modest clinical benefit from available therapies. Blockade of the inhibitory programmed death 1 (PD-1) receptor by monoclonal antibodies ...has been effective in several malignancies. Results from the prostate adenocarcinoma cohort of the nonrandomized phase Ib KEYNOTE-028 trial of pembrolizumab in advanced solid tumors are presented.
Key eligibility criteria included advanced prostate adenocarcinoma, unsuccessful standard therapy, measurable disease per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1), and PD-1 ligand (PD-L1) expression in ≥1% of tumor or stromal cells. Patients received pembrolizumab 10mg/kg every 2weeks until disease progression or intolerable toxicity for up to 24months. Primary end point was objective response rate (ORR) per RECIST v1.1 by investigator review.
Median patient age in this cohort (n=23) was 65years; 73.9% of patients received at least two prior therapies for metastatic disease. There were four confirmed partial responses, for an ORR of 17.4% 95% confidence interval (CI) 5.0%–38.8%; 8 of 23 (34.8%) patients had stable disease. Median duration of response was 13.5months. Median progression-free survival (PFS) and overall survival (OS) were 3.5 and 7.9months, respectively; 6-month PFS and OS rates were 34.8% and 73.4%, respectively. One patient remained on treatment at data cutoff. After a median follow-up of 7.9months, 14 (60.9%) patients experienced treatment-related adverse events (TRAEs), most commonly nausea (n=3, 13.0%). Four (17.3%) experienced grade 3/4 TRAEs: grade 3 peripheral neuropathy, grade 3 asthenia, grade 3 fatigue, and grade 4 lipase increase. No pembrolizumab-related deaths or discontinuations occurred.
Pembrolizumab resulted in durable objective response in a subset of patients with heavily pretreated, advanced PD-L1–positive prostate cancer, and its side effect profile was favorable.
NCT02054806
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Summary
In Asia, enthesitis‐related arthritis (ERA) is the most frequent category of juvenile idiopathic arthritis. ERA has a strong association with human leucocyte antigen (HLA)‐B27 and subclinical ...gut inflammation. In an HLA‐B27 transgenic rat model, the presence of Bacteroides bacteria in the gut appears to cause spondyloarthropathy (SpA). Thus, we studied gut microbiota in children with ERA. Stool specimens from 33 patients with ERA and 14 age‐matched healthy controls were studied; none had any gastrointestinal symptom, or had received a drug known to affect gut motility or microbiota in the preceding 6 weeks. From each specimen, a cDNA library for the V3 region of bacterial 16S rRNA was subjected to high‐throughput, massively parallel sequencing. Relationship of the specimens was studied using principal co‐ordinate analysis (PCoA), and abundances of various bacterial taxa and alpha diversity were compared between groups. In eight patients, a repeat faecal specimen was studied after 12 weeks of probiotic therapy. The 55 specimens yielded a median (range) of 397 315 (102 093–1 502 380) high‐quality reads each. In PCoA, gut microbiota from ERA showed a wider dispersion than those from controls. In patients, families Bacteroidaceae and Enterobacteriaceae were more abundant and Prevotellaceae were less abundant than in controls. Also, genera Bacteroides, Entercoccus and Klebsiella were over‐represented and genus Prevotella was under‐represented in ERA patients. Probiotic therapy led to a non‐significant increase in Prevotellaceae. Patients with ERA have a dysbiosis in the gut, with increased abundance of Bacteroides and reduction of Prevotella. Probiotic supplementation in a subset of patients did not reverse these changes significantly.
Gut microbiota from ERA showed a wider dispersion than those from controls
In patients, genera Bacteroides, Entercoccus and Klebsiella were overrepresented, and genus Prevotella was under‐represented
Probiotic therapy led to a non‐significant increase in Prevotellaceae.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Aim
The aim was to assess study factors that impact the association of cognitive disorders in people with periodontal disease (PD).
Method
Medline, EMBASE and Cochrane databases were ...searched until February 2022 using keywords and MeSH: (periodon* OR tooth loss OR missing teeth) AND (dementia OR Alzheimer’s Disease OR cognitive*). Observational studies reporting prevalence or risk of cognitive decline, dementia or Alzheimer’s disease (AD) in people with PD compared with healthy controls were included. Meta-analysis quantified the prevalence and risk (relative riskRR) of cognitive decline, dementia/AD, respectively. Meta-regression/subgroup analysis explored the impact of study factors including PD severity and classification type, and gender.
Results
Overall, 39 studies were eligible for meta-analysis: 13 cross-sectional and 26 longitudinal studies. PD demonstrated increased risks of cognitive disorders (cognitive decline—RR = 1.33, 95% CI = 1.13–1.55; dementia/AD—RR = 1.22, 95% CI = 1.14–1.31). Risk of cognitive decline increased with PD severity (moderate—RR = 1.14, 95% confidence interval CI = 1.07–1.22; severe—RR = 1.25, 95% CI = 1.18–1.32). For every 10% population increase in females, the risk of cognitive decline increased by 34% (RR = 1.34, 95% CI = 1.16–1.55). Self-reported PD showed a lower risk of cognitive disorders compared with clinical classification (cognitive decline—RR = 0.77, 95% CI = 0.65–0.91; dementia/AD—RR = 0.86, 95% CI = 0.77–0.96).
Conclusion
The prevalence and risk estimates of cognitive disorders in association with PD can be influenced by gender, the disease classification of PD and its severity. Further homologous evidence taking these study factors into consideration is needed to form robust conclusions.
Objectives
Cardiovascular disease (CVD) is a major cause of mortality; periodontal disease (PD) affects up to 50% of the world's population. Observational evidence has demonstrated association ...between CVD and PD. Absent from the literature is a systematic review and meta‐analysis of longitudinal cohort studies quantifying CVD risk in PD populations compared to non‐PD populations. To examine the risk of incident CVD in people with PD in randomised controlled trials and longitudinal cohort studies.
Material and Methods
We searched Medline, EMBASE and Cochrane databases up to 9th Oct 2019 using keywords and MeSH headings using the following concepts: PD, CVD, longitudinal and RCT study design. CVD outcomes included but were not restricted to any CVD, myocardial infarction, coronary heart disease (CHD) and stroke. Diagnosis method and severity of PD were measured either clinically or by self‐report. Studies comparing incident CVD in PD and non‐PD populations were included. Meta‐analysis and meta‐regression was performed to determine risk of CVD in PD populations and examine the effects of PD diagnosis method, PD severity, gender and study region.
Results
Thirty‐two longitudinal cohort studies were included after full text screening; 30 were eligible for meta‐analysis. The risk of CVD was significantly higher in PD compared to non‐PD (relative risk RR: 1.20, 95% CI: 1.14–1.26). CVD risk did not differ between clinical or self‐reported PD diagnosis (RR = 0.97, 95% CI: 0.87–1.07,). CVD risk was higher in men (RR: 1.16, 95% CI: 1.08–1.25) and severe PD (RR: 1.25, 95% CI: 1.15–1.35). Among all types of CVD, the risk of stroke was highest (RR = 1.24; 95% CI:1.12–1.38), the risk of CHD was also increased (RR = 1.14; 95% CI:1.08–1.21).
Conclusion
This study demonstrated modest but consistently increased risk of CVD in PD populations. Higher CVD risk in men and people with severe PD suggests population‐targeted interventions could be beneficial.
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CMK, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
This paper implements and evaluates the performance of a discriminatively trained continuous Hindi language speech recognition system. The system uses maximum mutual information and minimum phone ...error discriminative techniques with various numbers of Gaussian mixtures to train the automatic speech recognition (ASR) system. The training dataset consists of Hindi speech transcription. The experiments show a significant performance gain over maximum likelihood-based Hindi language speech recognition system. The system uses an efficient recurrent neural network (RNN)-based language modeling. The results indicate that the use of RNN-based language modeling enhances the performance of the ASR system. Further, the interpolation of
n
-gram language model (LM) with the RNNLM exhibits an additional increase in recognition performance of the implemented system. The proposed system introduces the concept of speaker adaption using maximum likelihood linear regression technique. The paper also gives an overview of the techniques used for discriminative training along with practical issues involved in their implementation.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, ODKLJ, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Native Sikkimese yak in Sikkim state of India is a pastoral treasure being raised through centuries-old transhumance practices and has evolved in response to natural and man-made selection. ...Currently, the population of Sikkimese yak is at risk with about five thousand total headcounts. Characterization is essential for taking appropriate decisions for conservation of any endangered population. In an attempt to phenotypically characterize the Sikkimese yaks, this study recorded phenotypic morphometric traits information, viz., body length (LG), height at withers (HT), heart girth (HG), paunch girth (PG), horn length (HL), horn circumference (HC), distance between horns (DbH), ear length (EL), face length (FL), face width (FW), and tail length with switch (TL), on 2154 yaks of both sexes. Multiple correlation estimation highlighted that HG and PG, DbH and FW, and EL and FW were highly correlated. Using principal component analysis, LG, HT, HG, PG, and HL were found to be the most important traits for phenotypic characterization of Sikkimese yak animals. Discriminant analysis based on different locations of Sikkim hinted at the existence of two separate clusters, however, broadly, phenotypic uniformity could be observed. Subsequent genetic characterization can offer greater insights and can pave the way for future breed registration and conservation of the population.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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