Category: Nevin Manimala

Cancer Sci. 2022 Feb 4. doi: 10.1111/cas.15291. Online ahead of print.

ABSTRACT

Immunotherapy is currently recognized as the fourth modality in cancer therapy. CTLs can detect cancer cells via complexes involving human leukocyte antigen (HLA) class I molecules and peptides derived from tumor antigens, resulting in antigen-specific cancer rejection. The peptides may be predicted in silico using machine learning-based algorithms. Neopeptides, derived from neoantigens encoded by somatic mutations in cancer cells, are putative immunotherapy targets, as they have high tumor specificity and immunogenicity. Here, we used our pipeline to select 278 neoepitopes with high predictive “SCORE” from the tumor tissues of 46 patients with hepatocellular carcinoma or metastasis of colorectal carcinoma. We validated peptide immunogenicity and specificity by in vivo vaccination with HLA-A2, A24, B35, and B07 transgenic mice using ELISpot assay, in vitro and in vivo killing assays. We statistically evaluated the power of our prediction algorithm and demonstrated the capacity of our pipeline to predict neopeptides (area under the curve = 0.687, p < 0.0001). We also analyzed the potential of long peptides containing the predicted neoepitopes to induce CTLs. Our study indicated that the short peptides predicted using our algorithm may be intrinsically present in tumor cells as cleavage products of long peptides. Thus, we empirically demonstrated that the accuracy and specificity of our prediction tools may be potentially improved in vivo using the HLA transgenic mouse model. Our data will help to feedback algorithms to improve in silico prediction, potentially allowing researchers to predict peptides for personalized immunotherapy.

PMID:35122353 | DOI:10.1111/cas.15291

Eur J Neurol. 2022 Feb 4. doi: 10.1111/ene.15271. Online ahead of print.

ABSTRACT

BACKGROUND: Successful long-term treatment of spasticity in people with multiple sclerosis (pwMS) is challenging. We investigated the effects of multidisciplinary inpatient rehabilitation (MIR) and an individualized self-training program delivered by an App on spasticity in pwMS.

METHODS: First we assessed the efficacy of 4-weeks MIR in ambulatory pwMS (EDSS<7.0) with moderate to severe lower limb spasticity (defined by ≥4 points on the Numeric Rating Scale for spasticity (NRSs)) in a cohort of 115 pwMS in 7 rehabilitation centers in Austria. In case of a clinically relevant improvement in spasticity of ≥20% on the NRSs following MIR (n=94), pwMS were randomly allocated in a 1:1 ratio to either a newly designed “MS-spasticity App” or to a paper-based self-training program for 12 weeks. The primary outcome was change in NRSs (DRKS00023960).

RESULTS: MIR led to a significant reduction of 2.0 points on the NRSs (95% Confidence Interval (CI) 2.5 to 2.0; p<0.000). MIR was further associated with a statistically significant improvement in spasticity on the modified Ashworth scale, strength and all mobility outcomes. Following MIR, self-training with “MS-spasticity App” was associated with a sustained positive effect on the NRSs, while paper-based self-training led to a worsening in spasticity (median NRSs difference 1.0; 95% CI 1.7 to 0.3; p=0.009). “MS-spasticity App” was also associated with a significantly better adherence to self-training (95% versus 72% completion rate; p<0.001).

CONCLUSION: In pwMS, MIR is able to significantly improve lower-limb spasticity, strength and mobility. Following MIR, an individually tailored anti-spasticity program delivered by an App leads to sustained positive long-term management.

PMID:35122365 | DOI:10.1111/ene.15271

Eur J Cancer Care (Engl). 2022 Feb 5:e13556. doi: 10.1111/ecc.13556. Online ahead of print.

ABSTRACT

OBJECTIVE: To report the uptake rate of cervical cancer screening (the Papanicolaou [Pap] test) and identify the perceived barriers associated with screening uptake among South Asian women in Hong Kong.

METHODS: This cross-sectional study involved a structured survey of 776 South Asian women aged 21 and above, recruited from the community. The participants’ demographic characteristics, Pap test uptake and responses to a validated 14-item scale of perceived barriers to screening was collected. The data were analysed using descriptive statistics and logistic regression.

RESULTS: The Pap test uptake rate was 40.3%. Multivariate analysis identified two perceived barriers significantly associated with the participants’ Pap test uptake: (1) not knowing where to have the test and (2) the belief that they did not need a test if they felt well.

CONCLUSION: Although language problems and embarrassment are commonly reported barriers to screening by South Asians, the participants were more concerned about where to have the test and whether they needed it. Future interventions should thus focus on enhancing their access to the service and clarifying their understanding of the need.

PMID:35122343 | DOI:10.1111/ecc.13556

Int J Paediatr Dent. 2022 Feb 4. doi: 10.1111/ipd.12955. Online ahead of print.

ABSTRACT

AIM: The aim of this in vitro study is to comparatively evaluate the band fit of the metallic band-loop space maintainers fabricated by conventional and 3D printing technology for clinical applications.

DESIGN: Sixteen digital intraoral impressions were selected and resin models were printed with 3D printer. Forty band-loop space maintainers were fabricated (n=20 for conventional group and n=20 for digital group). To evaluate the band fit of conventional and CAD/CAM fabricated space maintainers, cement space was visualized with low viscosity condensation silicone material on resin models. Digital evaluation was done by dual scan method superimposing two scans of resin models covered with or without a silicone layer on the abutment tooth. The mean quadratic deviation (Root Mean Square, RMS) was calculated. RMS values between the groups were evaluated with Student-t test. Statistical significance was set as p <0.05.

RESULTS: No statistical significance was found between the conventional and digital groups (p=0.56).

CONCLUSIONS: Within the limitations of this study, the band fit of conventional and CAD/CAM-fabricated space maintainers had no difference. There is a need for studies about CAD/CAM-fabricated appliances regarding other aspects such as fracture strength and patient comfort.

PMID:35122341 | DOI:10.1111/ipd.12955

Dig Endosc. 2022 Feb 4. doi: 10.1111/den.14244. Online ahead of print.

ABSTRACT

OBJECTIVE: Three high-risk flat and depressed lesions (FDLs), laterally spreading tumors non-granular type (LST-NG), depressed lesions, and large sessile serrated lesions (SSLs), are highly attributable to post-colonoscopy colorectal cancer (CRC). Efficient and organized educational programs on detecting high-risk FDLs are lacking. We aimed to explore whether a web-based educational intervention with training on FIND clues (fold deformation, intensive stool/mucus attachment, no vessel visibility, and demarcated reddish area) may improve the ability to detect high-risk FDLs.

METHODS: This was an international web-based randomized control trial that enrolled non-expert endoscopists in 13 Asian countries. The participants were randomized into either education or non-education group. All participants took the pre-test and post-test to read 60 endoscopic images (40 high-risk FDL, 5 polypoid, 15 no lesions) and answered whether there was a lesion. Only the education group received a self-education program (video and training questions and answers) between the tests. The primary outcome was a detection rate of high-risk FDLs.

RESULTS: In total, 284 participants were randomized. After excluding non-responders, the final data analyses were based on 139 participants in the education group and 130 in the non-education group. The detection rate of high-risk FDLs in the education group significantly improved by 14.7% (66.6% to 81.3%) compared with -0.8% (70.8% to 70.0%) in the non-education group. Similarly, the detection rate of LST-NG, depressed lesions, and large SSLs significantly increased only in the education group by 12.7%, 12.0%, and 21.6%, respectively.

CONCLUSION: Short self-education focusing on detecting high-risk FDLs was effective for Asian non-expert endoscopists. (UMIN000042348).

PMID:35122323 | DOI:10.1111/den.14244

J Eur Acad Dermatol Venereol. 2022 Feb 5. doi: 10.1111/jdv.17986. Online ahead of print.

ABSTRACT

BACKGROUND: Incidence of surgical site infection (SSI) following Mohs micrographic surgery (MMS) among patients with diabetes is largely unknown.

OBJECTIVE: Evaluate diabetes as a potential SSI risk factor in MMS by comparing SSI incidence in a cohort of patients with and without diabetes.

METHODS: 5-year retrospective review to determine SSI rate in patients with diabetes compared to patients without diabetes. SSI incidence in patients with diabetes was further compared by A1c, and the impact of antibiotics on SSI rate was also examined.

RESULTS: Overall rate of SSI was 1.47% (53/3,597 cases). SSI rate among patients with diabetes was 1.95% (14/719 cases) compared to 1.35% (39/2,878 cases) in patients without diabetes, with a non-significant odds ratio for SSI of 1.45 (95% CI = 0.78-2.68, p = 0.241). Multivariable logistic regression analysis revealed no difference in SSI. Stratification of diabetic patients by A1c into ≥7.0 and <7.0 compared to patients without diabetes yielded no statistically significant difference in SSI among all groups (p = 0.815). Whether an antibiotic was prescribed did not significantly impact SSI rate between groups.

CONCLUSION: No significant difference in postoperative SSI was found in patients with diabetes compared to patients without diabetes following MMS regardless of degree of glycemic control.

PMID:35122334 | DOI:10.1111/jdv.17986

Cogn Sci. 2022 Feb;46(2):e13102. doi: 10.1111/cogs.13102.

ABSTRACT

How does prior linguistic knowledge modulate learning in verbal auditory statistical learning (SL) tasks? Here, we address this question by assessing to what extent the frequency of syllabic co-occurrences in the learners’ native language determines SL performance. We computed the frequency of co-occurrences of syllables in spoken Spanish through a transliterated corpus, and used this measure to construct two artificial familiarization streams. One stream was constructed by embedding pseudowords with high co-occurrence frequency in Spanish (“Spanish-like” condition), the other by embedding pseudowords with low co-occurrence frequency (“Spanish-unlike” condition). Native Spanish-speaking participants listened to one of the two streams, and were tested in an old/new identification task to examine their ability to discriminate the embedded pseudowords from foils. Our results show that performance in the verbal auditory SL (ASL) task was significantly influenced by the frequency of syllabic co-occurrences in Spanish: When the embedded pseudowords were more “Spanish-like,” participants were better able to identify them as part of the stream. These findings demonstrate that learners’ task performance in verbal ASL tasks changes as a function of the artificial language’s similarity to their native language, and highlight how linguistic prior knowledge biases the learning of regularities.

PMID:35122322 | DOI:10.1111/cogs.13102

J Clin Lab Anal. 2022 Feb 5:e24258. doi: 10.1002/jcla.24258. Online ahead of print.

ABSTRACT

BACKGROUND: Calprotectin is a calcium-binding protein that can be measured in serum, plasma, and feces. Increased serum and plasma calprotectin concentrations have been found in chronic inflammatory rheumatic disorders. An analytical and clinical evaluation of the DiaSorin Liaison® fecal Calprotectin assay using LIAISON® XL was performed.

METHODS: The protocol included an analytical and clinical evaluation in which imprecision, the linearity of dilution, differences between serum and plasma samples and method comparison with CalproLab™ ELISA kit were assessed. Serum calprotectin concentrations in active (n = 26) and remission (n = 23) rheumatoid arthritis (RA) patients were compared.

RESULTS: The intra-day and inter-day analytical imprecision CVs ranged from 2.9% to 4.0% and 2.7% to 10.4%, respectively. Correlation between measured and expected values was high (R > 0.99), indicating good linearity. The Wilcoxon signed-rank test showed that serum and plasma matched samples presented statistically significant differences (p < 0.001) being the highest concentrations of calprotectin observed in serum samples. Deming regression equation was as follows: Diasorin calprotectin (μg/ml) = -0.32 (95% CI: -0.65 – -0.05) +1.58 (95% CI: 1.42-1.79).* Calprolab calprotectin (μg/ml). Significantly higher serum calprotectin levels were found in RA patients with active disease when compared to patients with low disease activity or in clinical remission (mean ± SD) [(3.35 μg/ml ± 1.55) vs. (1.63 μg/ml ± 0.52), p < 0.001] and these levels correlated well with all disease activity indices.

CONCLUSIONS: The DiaSorin Liaison® fecal Calprotectin assay adapted for serum samples showed adequate technical performances and the clinical performances were similar to other assays.

PMID:35122317 | DOI:10.1002/jcla.24258

Cogn Sci. 2022 Feb;46(2):e13100. doi: 10.1111/cogs.13100.

ABSTRACT

Humans have the ability to learn surprisingly complicated statistical information in a variety of modalities and situations, often based on relatively little input. These statistical learning (SL) skills appear to underlie many kinds of learning, but despite their ubiquity, we still do not fully understand precisely what SL is and what individual differences on SL tasks reflect. Here, we present experimental work suggesting that at least some individual differences arise from stimulus-specific variation in perceptual fluency: the ability to rapidly or efficiently code and remember the stimuli that SL occurs over. Experiment 1 demonstrates that participants show improved SL when the stimuli are simple and familiar; Experiment 2 shows that this improvement is not evident for simple but unfamiliar stimuli; and Experiment 3 shows that for the same stimuli (Chinese characters), SL is higher for people who are familiar with them (Chinese speakers) than those who are not (English speakers matched on age and education level). Overall, our findings indicate that performance on a standard SL task varies substantially within the same (visual) modality as a function of whether the stimuli involved are familiar or not, independent of stimulus complexity. Moreover, test-retest correlations of performance in an SL task using stimuli of the same level of familiarity (but distinct items) are stronger than correlations across the same task with stimuli of different levels of familiarity. Finally, we demonstrate that SL performance is predicted by an independent measure of stimulus-specific perceptual fluency that contains no SL component at all. Our results suggest that a key component of SL performance may be related to stimulus-specific processing and familiarity.

PMID:35122313 | DOI:10.1111/cogs.13100

Cogn Sci. 2022 Feb;46(2):e13094. doi: 10.1111/cogs.13094.

ABSTRACT

Children with developmental language disorder (DLD) served as a test case for determining the role of extant vocabulary knowledge, endogenous attention, and phonological working memory abilities in cross-situational word learning. First-graders (M_age = 7 years; 3 months), 44 with typical development (TD) and 28 with DLD, completed a cross-situational word-learning task comprised six cycles, followed by retention tests and independent assessments of attention, memory, and vocabulary. Children with DLD scored lower than those with TD on all measures of learning and retention, a performance gap that emerged in the first cycle of the cross-situational protocol and that we attribute to weaknesses in initial encoding. Over cycles, children with DLD learned words at a similar rate as their TD peers but they were less flexible in their strategy use, demonstrating a propose-but-verify approach but never a statistical aggregation approach. Also, they drew upon different mechanisms to support their learning. Attention played a greater role for the children with DLD, whereas extant vocabulary size played a greater role for the children with TD. Children navigate the problem space of cross-situational learning via varied routes. This conclusion is offered as motivation for theorists to capture all learners, not just the most typical ones.

PMID:35122309 | DOI:10.1111/cogs.13094