Tag: pubmed

Arch Pathol Lab Med. 2022 Mar 28. doi: 10.5858/arpa.2021-0329-OA. Online ahead of print.

ABSTRACT

CONTEXT.—: Multiplex stool polymerase chain reaction tests (SPTs) simultaneously test for many enteric pathogens. However, the clinical significance of a positive result, particularly in the context of chronic gastrointestinal disease, remains controversial.

OBJECTIVE.—: To determine whether SPT results correlate with findings on colon biopsies obtained within a week of SPT or with clinical features.

DESIGN.—: We reviewed 261 colon biopsies during a 15-month period that were obtained within a week of SPT, along with available clinical information, from patients with and without chronic idiopathic inflammatory bowel disease (CIIBD). Statistical analysis was used to test associations between SPT result, histologic features, and clinical variables.

RESULTS.—: The most commonly detected pathogens were Clostridium difficile, enteropathogenic Escherichia coli, and norovirus. The presence of underlying CIIBD did not correlate with a positive SPT result or with a specific pathogen. Positive SPT result was significantly associated with neutrophilic activity, pseudomembranes, and increased intraepithelial lymphocytes. In addition, the presence of C difficile on SPT was significantly associated with pseudomembranes and neutrophilic activity. There were no other statistically significant relationships between SPT result and any other histologic abnormality. Only about half of SPT positive results were acted on clinically, and most patients with CIIBD were managed as having a presumed IBD flare.

CONCLUSIONS.—: SPTs have many advantages; however, interpretation of results, particularly in the background of chronic gastrointestinal disease, remains a challenge. Therapeutic decisions influenced by a positive SPT result should integrate biopsy findings, clinical data, and other laboratory testing to avoid inappropriate treatment.

PMID:35344996 | DOI:10.5858/arpa.2021-0329-OA

Neural Comput. 2022 Mar 23:1-36. doi: 10.1162/neco_a_01490. Online ahead of print.

ABSTRACT

Classification problems in the small data regime (with small data statistic T and relatively large feature space dimension D) impose challenges for the common machine learning (ML) and deep learning (DL) tools. The standard learning methods from these areas tend to show a lack of robustness when applied to data sets with significantly fewer data points than dimensions and quickly reach the overfitting bound, thus leading to poor performance beyond the training set. To tackle this issue, we propose eSPA+, a significant extension of the recently formulated entropy-optimal scalable probabilistic approximation algorithm (eSPA). Specifically, we propose to change the order of the optimization steps and replace the most computationally expensive subproblem of eSPA with its closed-form solution. We prove that with these two enhancements, eSPA+ moves from the polynomial to the linear class of complexity scaling algorithms. On several small data learning benchmarks, we show that the eSPA+ algorithm achieves a many-fold speed-up with respect to eSPA and even better performance results when compared to a wide array of ML and DL tools. In particular, we benchmark eSPA+ against the standard eSPA and the main classes of common learning algorithms in the small data regime: various forms of support vector machines, random forests, and long short-term memory algorithms. In all the considered applications, the common learning methods and eSPA are markedly outperformed by eSPA+, which achieves significantly higher prediction accuracy with an orders-of-magnitude lower computational cost.

PMID:35344997 | DOI:10.1162/neco_a_01490

Neural Comput. 2022 Mar 23:1-7. doi: 10.1162/neco_a_01494. Online ahead of print.

ABSTRACT

In this short note, we reify the connection between work on the storage capacity problem in wide two-layer treelike neural networks and the rapidly growing body of literature on kernel limits of wide neural networks. Concretely, we observe that the “effective order parameter” studied in the statistical mechanics literature is exactly equivalent to the infinite-width neural network gaussian process kernel. This correspondence connects the expressivity and trainability of wide two-layer neural networks.

PMID:35344992 | DOI:10.1162/neco_a_01494

Neural Comput. 2022 Mar 23:1-36. doi: 10.1162/neco_a_01491. Online ahead of print.

ABSTRACT

With the accelerated development of neural recording technology over the past few decades, research in integrative neuroscience has become increasingly reliant on data analysis methods that are scalable to high-dimensional recordings and computationally tractable. Latent process models have shown promising results in estimating the dynamics of cognitive processes using individual models for each neuron’s receptive field. However, scaling these models to work on high-dimensional neural recordings remains challenging. Not only is it impractical to build receptive field models for individual neurons of a large neural population, but most neural data analyses based on individual receptive field models discard the local history of neural activity, which has been shown to be critical in the accurate inference of the underlying cognitive processes. Here, we propose a novel, scalable latent process model that can directly estimate cognitive process dynamics without requiring precise receptive field models of individual neurons or brain nodes. We call this the direct discriminative decoder (DDD) model. The DDD model consists of (1) a discriminative process that characterizes the conditional distribution of the signal to be estimated, or state, as a function of both the current neural activity and its local history, and (2) a state transition model that characterizes the evolution of the state over a longer time period. While this modeling framework inherits advantages of existing latent process modeling methods, its computational cost is tractable. More important, the solution can incorporate any information from the history of neural activity at any timescale in computing the estimate of the state process. There are many choices in building the discriminative process, including deep neural networks or gaussian processes, which adds to the flexibility of the framework. We argue that these attributes of the proposed methodology, along with its applicability to different modalities of neural data, make it a powerful tool for high-dimensional neural data analysis. We also introduce an extension of these methods, called the discriminative-generative decoder (DGD). The DGD includes both discriminative and generative processes in characterizing observed data. As a result, we can combine physiological correlates like behavior with neural data to better estimate underlying cognitive processes. We illustrate the methods, including steps for inference and model identification, and demonstrate applications to multiple data analysis problems with high-dimensional neural recordings. The modeling results demonstrate the computational and modeling advantages of the DDD and DGD methods.

PMID:35344988 | DOI:10.1162/neco_a_01491

Audiol Neurootol. 2022 Mar 28:1-8. doi: 10.1159/000522566. Online ahead of print.

ABSTRACT

INTRODUCTION: The rates of cochlear nerve abnormalities and cochlear malformations in pediatric unilateral hearing loss (UHL) are conflicting in the literature, with important implications on management. The aim of this study was to investigate the incidence of cochlear nerve deficiency (CND) in pediatric subjects with UHL or asymmetric hearing loss (AHL).

METHODS: A retrospective chart review of pediatric subjects <18 years of age evaluated for UHL or AHL with fine-cut heavily T2-weighted magnetic resonance imaging (MRI) between January 2014 and October 2019 (n = 291) at a tertiary referral center was conducted. MRI brain and computed tomography temporal bone were reviewed for the presence of inner ear malformations and/or CND. Status of the ipsilateral cochlear nerve and inner ear was evaluated. Pure tone average (PTA) at 500, 1,000 and 2,000 Hz was assessed.

RESULTS: 204 subjects with UHL and 87 subjects with AHL were included. CND (aplasia or hypoplasia) was demonstrated in 61 pediatric subjects with UHL (29.9%) and 10 with AHL (11.5%). Ipsilateral cochlear malformations were noted in 25 subjects with UHL (12.3%) and 11 with AHL (12.6%), and ipsilateral vestibular malformations in 23 (11.3%) and 12 (13.8%) ears, respectively. Median PTA was statistically significantly higher in ears with CND (98.33) than ears with normal nerves (90.84).

DISCUSSION/CONCLUSION: Imaging demonstrated a high incidence of inner ear malformations, particularly CND, in pediatric subjects with UHL. Auditory findings indicated CND cannot be ruled out by thresholds alone as some CND ears did demonstrate measurable hearing. Radiologic evaluation by MRI should be performed in all patients within this population to guide counseling and management of hearing loss based on etiology, with implications on candidacy for cochlear implantation.

PMID:35344959 | DOI:10.1159/000522566

Oncology. 2022 Mar 28. doi: 10.1159/000524340. Online ahead of print.

ABSTRACT

BACKGROUND: In patients with hormone receptor positive metastatic breast cancer, Palbociclib has been shown to improve overall survival and progression-free survival (PFS) when combined with endocrine therapy. Dose modification of palbociclib is effective in the management of adverse events. Despite variable clinical response, no predictive biomarkers of efficacy to palbociclib have been identified in metastatic breast cancer. In our study, we aimed to assess the PFS of metastatic breast cancer patients who received dose-reduced palbociclib and compare the results in the non-dose reduced group. We also evaluated the clinical significance of progesterone receptor (PR) and Ki67 as predictive biomarkers of palbociclib.

METHODS: Seventy-six palbociclib-treated metastatic breast cancer patients were included in our study. PFS was compared between dose reduced and non-dose reduced groups. PR expression and Ki67 status were assessed by immunohistochemistry (IHC). Kaplan-Meier method and log-rank test were used to analyze PFS.

RESULTS: Of the 76 patients, 40 (52.6%) experienced dose reduction. Statistical analysis of the results revealed that there were no statistically significant differences observed between dose-reduced (16.5 months) vs non-dose reduced (17.7 months) patients in PFS (p=0.5493). For patients with Ki67 ≥ 14%, PFS was 15.2 months (95% CI: 10.2 to 22.2 months; p= 0.3024). In patients with PR ≥ 20%, median PFS was 25.0 months (lower 95% CI: 16.8 months; p=0.0069).

CONCLUSION: Our study indicated that dose reduction of palbociclib is frequently required but does not appear to affect PFS. PR expression was suggested to be a significant predictive factor for palbociclib responsiveness.

PMID:35344965 | DOI:10.1159/000524340

Tuberculosis (Edinb). 2022 Mar 18;134:102198. doi: 10.1016/j.tube.2022.102198. Online ahead of print.

ABSTRACT

Transient transfection of the respiratory mucosa of mice infected with Mycobacterium tuberculosis (Mtb) with gamma interferon (IFN-γ) promises benefits in disease therapy. We investigated preclinical efficacy of a dry powder inhalation (DPI) as a stand-alone versus adjunct to oral anti-tuberculosis (TB) chemotherapy in mice. We observed that this host-directed therapy mitigates the gross organ pathology and histopathology of lung and spleen tissue of infected mice receiving the DPI, either alone or as adjunct therapy. However, no statistically significant reduction in Mtb colony forming units (CFU) occurred if mice were given only DPI; but not drugs. We compared one and three doses a week of the DPI over four weeks; with or without concomitant oral drugs. There was no significant difference in lung CFU after four or 12 doses of the DPI alone, but, surprisingly, four doses were qualitatively better than 12 doses in mitigating lung pathology. Nodular lesions on the lung surface and the area occupied by these was significantly reduced after four doses of the DPI, even without oral drugs. Transient transfection with IFN-γ did not induce pathological inflammation of the lungs and airways. We conclude that IFN-γ, as expected of host-directed therapy, ‘heals the host; ‘ but does not ‘kill the bug.’

PMID:35344918 | DOI:10.1016/j.tube.2022.102198

Eur J Radiol. 2022 Mar 9;150:110227. doi: 10.1016/j.ejrad.2022.110227. Online ahead of print.

ABSTRACT

PURPOSE: To determine the normal thickness and MRI appearance of the Tibialis Posterior Tendon near the navicular insertion in normal volunteers.

MATERIALS AND METHODS: By using a 3T MRI system 41 ankles were imaged, and PD weighted images with fat saturation were acquired in the three orthogonal planes. Symptoms of tendon pathology and history of trauma or surgery of the tendon were used as volunteer exclusion criteria. Two different measurement points were determined to evaluate hyperintensity and thickness. Two radiologists assessed the internal signal of the Tibialis Posterior Tendon independently by using axial and coronal images. Tendon hyperintensity was classified from homogenously dark to different degrees of hyperintense signal, where 0 means no internal hyperintensity, 1 – minimal hyperintensity, 2 – moderate and 3 – marked. Correlations between the two observers were obtained by Cohen’s kappa. Descriptive statistics were also obtained.

RESULTS: Eight men and 13 women (total 21) volunteers, age range 19-43(average 24.7)years were included in the study. At measurement point-1 on the coronal images, observer-1 and observer-2 evaluated hyperintensity (mostly minimal) respectively in 90.5% and 95.3% of tendons with a Cohen’s kappa coefficient of 0.701 (moderate agreement) for the right foot and in 60% and 70% of tendons with a Cohen’s kappa coefficient of 0.624 (moderate agreement) for the left foot. On axial images both observers assessed hyperintensity (mostly marked) in 100% of the tendons with a coefficient of 0.763 (moderate agreement) for the right foot, and in 95% of tendons with a coefficient of 0.839 (strong agreement) for the left foot. At measurement point-2 on coronal images, both observers rated any degree of hyperintensity in 33.3% of tendons with a coefficient of 1.00 (perfect agreement) for the right foot, in 38.9% of tendons with a coefficient of 0.766 (moderate agreement) for the left foot. On axial images both observers evaluated hyperintensity (mostly minimal) in 100% of tendons with a kappa coefficient of 0.702 (moderate agreement) for the right foot, in 95% of tendons with a coefficient of 0.790 (moderate- to strong agreement) for the left foot.

CONCLUSION: The Tibialis Posterior Tendon, near the navicular insertion (navicular tendon and tarsometatarsal tendon), exhibits an apparent thickening and most importantly hyperintensity which should be regarded as a normal finding, and not lead to an erroneous diagnosis of tendinopathy. This observation was almost always the case for the navicular insertion and less so for the tarsometatarsal tendon.

PMID:35344915 | DOI:10.1016/j.ejrad.2022.110227

Mult Scler Relat Disord. 2022 Mar 15;61:103743. doi: 10.1016/j.msard.2022.103743. Online ahead of print.

ABSTRACT

BACKGROUND: Multiple Sclerosis (MS) is a chronic debilitating neurological disease affecting young adults. The disease involves immune-mediated demyelination of nerve fibers and neurons that leads to disruption of brain-body communication, leading to permanent nerve damage. MS-associated retrovirus envelope protein (MSRV-Env) has been detected in the blood and lesions of MS patients, and its role is suggested in the pathogenesis of MS. Temelimab is a humanized IgG4 monoclonal antibody (mAb) that targets the MSRV-Env protein and neutralizes its action. Several clinical trials have been conducted to evaluate the effectiveness of the drug in MS.

MATERIALS AND METHODS: A systemic search was conducted from electronic databases (PubMed/Medline, Cochrane Library, and Google Scholar) from inception to 11th sept 2021. All statistical analysis was conducted in Review Manager 5.4.1. Studies meeting inclusion criteria were selected. Those studies were selected which compared Temelimab therapy to inactive control. The primary outcome of interest was drug safety and efficacy; information about immunogenicity was also included. Random-effect model was used to pool the studies, and the result was reported in the risk ratio (RR) with corresponding 95% Confidence interval (CI).

RESULTS: Phase I, Phase II-a and Phase II-b trials demonstrate the safety and effectiveness of Temelimab. Our analysis showed statistically non-significant Risk Ratio (RR) of Adverse events in Temelimab group than that in placebo group (1.01 [0.70,1.46]; p-value = 0.94; I² = 0%) . Considering the effect of Temelimab on brain lesions, pooled result showed statistically significant Risk Ratio (RR) of brain lesions in placebo group than that in Temelimab group (0.75 [0.69,0.81), p-value < 0.00001, I² = 0% CONCLUSION: Qualitative and quantitative analysis of the trials assessing the safety and efficacy of Temelimab demonstrate that the drug is safe as well as favourable for use in MS patients.

PMID:35344907 | DOI:10.1016/j.msard.2022.103743

Mult Scler Relat Disord. 2022 Mar 5;61:103726. doi: 10.1016/j.msard.2022.103726. Online ahead of print.

ABSTRACT

BACKGROUND: Rehabilitation treatment may alleviate the disease severity of patients with NMOSD. The reports of rehabilitation exercise for NMOSD during acute phase are rare.

OBJECTIVE: To explore the efficacy and safety of rehabilitation exercise in patients with NMOSD during acute phase.

METHODS: This is a prospective cohort study of 36 patients (rehabilitation exercise group, RG) and 37 patients (control group, CG) in whom acute attack of NMOSD involved the spinal cord with EDSS≥4.5 were included. EDSS, American Spinal Injury Association Impairment Scale (AIS) grade, total motor score (TMS), light touch score (LTS), pin prick score (PPS), Berg balance scale (BBS), and Barthel index (BI) were used as outcome measures.

RESULTS: During hospitalization, EDSS scores of both groups decreased significantly (P<0.05). After treatment, the decline in EDSS was more significant in RG than in CG (P<0.05). The change reaching minimal clinically important difference (MCID) was observed in 90% (9/10) of patients in RG and in 27.78% (5/18) of patients in CG in the subgroup with EDSS 4.5-6.0 (MCID, 1.0), which was statistically significant between the groups (P<0.05). In the subgroup with EDSS 6.5-10.0 (MCID, 0.5), the proportion of patients with the change that reached MCID was significantly different between CG and RG (P<0.05). BBS, TMS, and BI score significantly improved after treatment (P<0.001). The improvement ranges of BBS, TMS, and BI scores were more significant in RG than CG (P<0.05). AIS grade improvement in RG was significantly higher than in CG. There were no significant changes in LTS and PPS after treatment in either of the groups. In RG, two mild adverse events were recorded.

CONCLUSION: Rehabilitation exercise may improve nervous system function, balance function, and activities of daily living in patients with acute NMOSD, with few adverse reactions.

PMID:35344908 | DOI:10.1016/j.msard.2022.103726