Voxel Based Morphometry (VBM) studies typically involve a comparison between groups of individuals; this approach however does not allow inferences to be made at the level of the individual. In ...recent years, an increasing number of research groups have attempted to overcome this issue by performing single case studies, which involve the comparison between a single subject and a control group. However, the interpretation of the results is problematic; for instance, any significant difference might be driven by individual variability in neuroanatomy rather than the neuropathology of the disease under investigation, or might represent a false positive due to the data being sampled from non-normally distributed populations. The aim of the present investigation was to empirically estimate the likelihood of detecting significant differences in gray matter volume in individuals free from neurological or psychiatric diagnosis. We compared a total of 200 single subjects against a group of 16 controls matched for age and gender, using two independent datasets from the Neuroimaging Informatics Tools and Resources Clearinghouse. We report that the chance of detecting a significant difference in a disease-free individual is much higher than previously expected; for instance, using a standard voxel-wise threshold of p<0.05 (corrected) and an extent threshold of 10 voxels, the likelihood of a single subject showing at least one significant difference is as high as 93.5% for increases and 71% for decreases. We also report that the chance of detecting significant differences was greatest in frontal and temporal cortices and lowest in subcortical regions. The chance of detecting significant differences was inversely related to the degree of smoothing applied to the data, and was higher for unmodulated than modulated data. These results were replicated in the two independent datasets. By providing an empirical estimation of the number of significant increases and decreases to be expected in each cortical and subcortical region in disease-free individuals, the present investigation could inform the interpretation of future single case VBM studies.
► Single subject VBM shows high false positive rates in the healthy population. ► Differences in single subjects are more likely to reflect increases than decreases. ► Differences are mainly located in frontal and temporal areas of the neocortex. ► Single subject VBM studies of patients should be interpreted with caution.
Merkel cell carcinoma (MCC) is a rare aggressive neuroendocrine cutaneous carcinoma with a high mortality rate. The MCC etiology is not fully understood. Merkel cell-associated polyomavirus (MCPyV) ...was found in MCC patients, indicating a risk factor for the tumor. Caucasian, elderly, and immunocompromised individuals are more likely to develop this tumor. HLA-G consists of a non-classical class I (Ib) HLA molecule with an immunoregulatory function and was associated with tumor escape in different types of tumors, nonetheless, never been studied in MCC. The purpose of this study was to evaluate the HLA-G expression and also to detect the MCPyV in MCC patients and correlate it with the clinical course of the disease. Forty-five MCC patients were included in a retrospective study. Formalin-fixed paraffin-embedded cutaneous skin biopsies were used by immunohistochemistry and RT-PCR to verify the HLA-G expression and MCPyV infection. HLA-G expression was found in 7 (15.6%), while the presence of MCPyV was detected in 28 (62.2%) of the studied patients. No significant association was found between HLA-G expression and MCPyV infection (
p
= 0.250). The presence of MCPyV was associated with areas of low sunlight exposure (
p
= 0.042) and the HLA-G expression with progression to death (
p
= 0.038). HLA-G expression was detected in MCC patients, as well as the MCPyV presence was confirmed. These markers could represent factors with a possible impact on patient survival; however, further studies with a greater number of patients are needed, to better elucidate the possible role in disease progression.
To analyze a multi-institutional series of type C thymic carcinomas (TCs) (including neuroendocrine tumors), focusing on the expression and mutations of c-KIT.
Immunohistochemical expression of ...c-KIT/CD117, p63, CD5 and neuroendocrine markers, as well as mutational analysis of c-KIT exons 9, 11, 13, 14, 17 by direct sequencing of 48 cases of TCs. Immunohistochemical and molecular data were statistically crossed with clinicopathological features.
Overall, 29 tumors (60%) expressed CD117, 69% were positive for CD5 and 85% (41 cases) for p63. Neuroendocrine markers stained all six atypical carcinoids and five poorly-differentiated thymic squamous cell carcinomas. Overall, six CD117-positive cases (12.5%) showed c-KIT mutation. No mutation was detected in CD117-negative tumors and carcinoids. All the mutations were found in poorly-differentiated thymic squamous cell carcinomas expressing CD117, CD5, p63 and lacking neuroendocrine markers (6 of 12 cases with these features). Mutations involved exon 11 (four cases: V559A, L576P, Y553N, W557R), exon 9 (E490K) and exon 17 (D820E).
All TCs need an immunohistochemical screening with CD117, while c-KIT mutation analysis is mandatory only in CD117-positive cases, particularly when coexpressing CD5 and p63, lacking neuroendocrine differentiation. The finding of c-KIT mutation can predict efficacy with different c-KIT inhibitors.
Objective
To evaluate partial HPV16/18 genotyping as a possible biomarker to select women attending HPV‐based cervical cancer screening at higher risk to be referred to colposcopy.
Design
...Population‐based cohort study.
Setting
Organised cervical cancer screening programmes (Italy).
Population
Women with high‐risk HPV infection (period: 2015–2019).
Methods
We analysed the association between partial HPV16/18 genotyping, cytology triage and histologically confirmed diagnosis of high‐grade cervical intraepithelial neoplasia (CIN3+) lesions.
Main outcome measures
Detection rate (DR) and positive predictive value (PPV) for histologically confirmed CIN3+ (any episode in the 2 years after baseline); sensitivity for CIN3+ and number of colposcopies needed for lesion detection.
Results
The study included 145 437 women screened with HPV testing by the clinically validated COBAS 4800 HPV assay (Roche). Overall, 9601 (6.6%) women were HPV+ at baseline; HPV16 and HPV18 were present in 1865 and 594 samples, respectively. The cumulative (baseline plus 1‐year repeat) cytology positivity was 42.8% and high‐grade cytology was significantly higher (P < 0.0001) among women with HPV16 infection at baseline (15.2%). The cumulative CIN3+ DR for women with HPV16, HPV18 and other HPV‐type infections was 9.8%, 3.4% and 1.8%, respectively.
Conclusions
Partial HPV16 genotyping may play a role in triage, whereas HPV18 seems to behave much more similarly to the other HPV types and does not provide additional stratification. HPV16 genotyping combined with high‐grade cytology can be envisaged as a triage biomarker in cervical screening to maximise CIN3+ detection while minimising colposcopy at baseline or 1‐year repeat.
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HPV16 genotyping combined with high‐grade cytology can be used as triage biomarker for CIN3+ in HPV‐positive women.
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HPV16 genotyping combined with high‐grade cytology can be used as a triage biomarker for CIN3+ in HPV‐positive women.
To describe the decay stage of coarse woody debris (CWD) a five decay-class system has been introduced and it is currently the most commonly applied. This system is based on visual, geometric and ...tactile features of the wood in the field; however, a detailed chemical characterization is often missing. Furthermore, the driving mechanisms (particularly substrate quality vs. environmental conditions) of deadwood decay are controversially discussed. Consequently, we investigated how typical major and minor chemical parameters of wood were correlated with the decay stage. The decomposition patterns of Norway spruce (Picea abies (L.) Karst) and European larch (Larix decidua Mill.) CWD of an Alpine setting were analyzed, and how the chemical and physical parameters were affected by the substrate and environmental conditions was checked. Two altitudinal sequences, having a different exposure (north- vs. south-facing sites), were sampled. We measured main biochemical compounds (lignin and cellulose), physical properties (density and water content), element concentrations (C, N, P, K, Ca, Mg, Fe, Mn), and the carbon isotopic signature (δ13C) of living trees and CWD at five decomposition stages (decay classes). Most investigated wood physico-chemical parameters such as wood density, water content, lignin and cellulose and even minor constituents (N, Ca, Mg, P, Fe, Mn) correlated well to the five decay-class system. Some important components, such as the carbon concentration and δ13C, did not vary with increasing decomposition. Our hypothesis that the different substrate should be traceable during CWD decay had to be rejected, although some statistically significant chemical differences between larch and spruce were measured in the living trees. The chosen tree species were probably not different enough to be chemically traceable in the CWD. Already in decay class 1, these differences were zeroed. The site conditions (expressed by the different altitudes and exposure) influenced only some of the investigated parameters, namely lignin, the δ13C isotopic ratio and nutrients such as P, Ca and K.
Introduction and hypothesis
The aim of the study was to compare the efficacy and safety of transvaginal trocar-guided polypropylene mesh insertion with traditional colporrhaphy for treatment of ...anterior vaginal wall prolapse.
Methods
This is a randomized controlled trial in which women with advanced anterior vaginal wall prolapse, at least stage II with Ba ≥ +1 cm according to the Pelvic Organ Prolapse Quantification (POP-Q) classification, were randomly assigned to have either anterior colporrhaphy (
n
= 39) or repair using trocar-guided transvaginal mesh (
n
= 40). The primary outcome was objective cure rate of the anterior compartment (point Ba) assessed at the 12-month follow-up visit, with stages 0 and I defined as anatomical success. Secondary outcomes included quantification of other vaginal compartments (POP-Q points), comparison of quality of life by the prolapse quality of life (P-QOL) questionnaire, and complication rate between the groups after 1 year. Study power was fixed as 80 % with 5 % cutoff point (
p
< 0.05) for statistical significance.
Results
The groups were similar regarding demographic and clinical preoperative parameters. Anatomical success rates for colporrhaphy and repair with mesh placement groups were 56.4 vs 82.5 % (95 % confidence interval 0.068–0.54), respectively, and the difference between the groups was statistically significant (
p
= 0.018). Similar total complication rates were observed in both groups, with tape exposure observed in 5 % of the patients. There was a significant improvement in all P-QOL domains as a result of both procedures (
p
< 0.001), but they were not distinct between groups (
p
> 0.05).
Conclusions
Trocar-guided transvaginal synthetic mesh for advanced anterior POP repair is associated with a higher anatomical success rate for the anterior compartment compared with traditional colporrhaphy. Quality of life equally improved after both techniques. However, the trial failed to detect differences in P-QOL scores and complication rates between the groups.
This study focuses on the biological and morphological development of humus profiles in forested Italian Alpine soils as a function of
climate
. Humus form description, systematic investigation of ...microannelid communities and polyphasic biochemical fingerprinting of soil microbial communities (denaturing gradient gel electrophoresis (DGGE) and phospholipid fatty acid analysis (PLFA)) were performed to compare sites differing in mean annual temperature due to different altitude and exposure. Although the soil biota showed complex responses, several differences in soil biological properties seem to be due to thermal differences. Although soil acidity also determines biological properties, it is not a state factor but rather influenced by them. The thickness of the organic layer and the acidification of the subjacent mineral horizon increased under cooler conditions (north-exposure; higher altitude), whereas the thickness of the A horizon inversely decreased. Species richness of microannelid assemblages was higher under warmer conditions (south-exposure; lower altitude) and the vertical distribution of microannelids shifted along the gradient to lower temperatures from predominant occurrence in the mineral soil to exclusive occurrence in the organic layer. Microbial biomass (total PLFA) was higher at the cooler sites; the prevalence of Gram-negative bacteria could be ascribed to their better adaptation to lower temperature, pH and nutrient contents. The δ
13
C signatures of the PLFA markers suggested a lower decomposition rate at the cooler sites, resulting in a lower respiratory loss and an accumulation of weakly decomposed organic material. DGGE data supported the PLFA results. Both parameters reflected the expected thermal sequence. This multidisciplinary case study provided indications of an association of
climate
, mesofauna and microbiota using the humus form as an overall link. More data are however needed and further investigations are encouraged.
Summary
A variety of fungal pulmonary infections can produce radiologic findings that mimic lung cancers. Distinguishing these infectious lesions from lung cancer remains challenging for radiologists ...and clinicians. In such cases, radiographic findings and clinical manifestations can be highly suggestive of lung cancer, and misdiagnosis can significantly delay the initiation of appropriate treatment. Likewise, the findings of imaging studies cannot replace the detection of a species as the aetiological agent. A biopsy is usually required to diagnose the infectious nature of the lesions. In this article, we review the clinical, histologic and radiologic features of the most common fungal infections that can mimic primary lung cancers, including paracoccidioidomycosis, histoplasmosis, cryptococcosis, coccidioidomycosis, aspergillosis, mucormycosis and blastomycosis.
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