Synthesis and Reactivity of Base-Stabilized and Base-Free Silaimidoyl Bromides.

The reactivity of the base-free bromosilylene dtbpCbzSiBr (dtbpCbz = 1,8-bis(3,5-di-tert-butylphenyl)-3,6-di-tert-butylcarbazolyl) toward carbodiimides and azides was studied in order to generate base-stabilized and base-free silaimidoyl bromides, respectively. The steric bulk of carbodiimides and azides allows control over the reactivity. While with small substituents such as tert-butyl or adamantyl, the reactions cannot be stopped at the Si═N stage, with large substituents, they lead to C-H activation in the product. The Dipp substituent (Dipp = 2,6-diisopropylphenyl) allowed the isolation of the silaimidoyl bromide dtbpCbzSi(Br)NDipp and its CNDipp-coordinated analogue. The reactivity of the Si═N double bond species was studied with respect to cycloaddition and donor exchange reactions.

Ureterorenoscopic Stone Removal without Antibiotic Prophylaxis.

INTRODUCTION: The aim of this study was to assess the feasibility of sparing routine antibiotic prophylaxis in patients without preoperative urinary tract infection undergoing ureterorenoscopy (URS) for stone removal. METHODS: A retrospective, monocentric study was conducted to evaluate the outcome of a modified perioperative antibiotic management strategy according to the principles of antibiotic stewardship. Patients with preoperative unremarkable urine culture received no antibiotic prophylaxis for URS stone removal (NoPAP). The NoPAP group was compared to a historic URS cohort, when antibiotic prophylaxis (PAP) was standard of care. Analysis focused on postoperative complications. RESULTS: Postoperative fever occurred in 1% of the NoPAP and 2% of the PAP patients (p = 0.589). Clavien 1-3 complications did not differ between groups with 9% in the NoPAP and 6.2% in the PAP (p = 0.159). No Clavien 4-5 complications were seen. We identified a residual stone (p = 0.033) and an ASA score 3-4 (p = 0.004) as significant risk factors for postoperative fever. By sparing routine antibiotic prophylaxis, the overall antibiotic usage was reduced from 100% (PAP) to 8.3% (NoPAP). CONCLUSION: Sparing a routine antibiotic prophylaxis during URS for stone removal seems feasible in patients with unremarkable preoperative urine culture for most of the patients. A prospective validation is warranted.

Impact of SARS-CoV-2-Pandemic on diagnosis of prostate cancer.

Introduction The aim of this study was to prove if the SARS-CoV-2-pandemic resulted in a delay in diagnosis and treatment of prostate cancer (PC). Methods A monocentric, retrospective analysis was conducted at a university cancer center. Included were all patients with untreated PC diagnosed between January 2019 and December 2021. The observation covered 22 months of the SARS-CoV-2-pandemic and 14 months preceding it. Results 969 men prior (T0) and 1343 during pandemic (T1) where included. Mean age was 68.0 (SD 8.2). Median initial PSA was 8.1 ng/ml (T0) and 7.9 ng/ml (T1, p= 0.288). Time from biopsy to tumor board (T0: 1.3 months vs. T1: 0.9 months, p=0.001), to staging (T0: 1,1 months vs. T1: 0.75 months, p=0.707) and to therapy (T0: 3.0 months vs. T1: 2.0 months, p<0.001) were shortened during pandemic. Classified by d'Amico, a significant shift towards higher risk groups was seen (p=0.024). Local staging showed an insignificant increase in locally advanced PCs. Metastatic diseases decreased from 10.3 % to 8.9% (p=0.433). Pathological staging showed pT3+ in 44.4% vs. 44.7% (p=0.565) and pN+ in 9.9 % vs 9.6% (p=0.899). Conclusion Regarding the diagnosis and treatment of PC, we could not demonstrate any delays due to the SARS-CoV-2-pandemic.

Silylenes with a Small Chalcogenide Substituent: Tuning Frontier Orbital Energies from O to Te.

The general synthesis of heteroleptic acyclic silylenes with a bulky carbazolyl substituent (dtbpCbz) is detailed and a series of compounds with a chalcogenide substituent of the type [(dtbpCbz)SiE16R] (E16R=OtBu, SEt, SePh, TePh) is reported. With the bulky carbazolyl substituent present, the chalcogenide moiety can be very small, as is shown by incorporating groups as small as ethyl, phenyl or tert-butyl. For the first time, the electronic properties of the silylene can be tuned along a complete series of chalcogenide substituents. The effects are clearly visible in the NMR and UV/Vis spectra, and were rationalised by DFT computations. The reactivity of the heaviest chalcogenide-substituted silylenes was probed by reactions with trimethylphosphine selenide and the terphenyl azide TerN3 (Ter=2,6-dimesitylphenyl).

Strain-Driven, Non-Catalysed Ring Expansion of Silicon Heterocycles.

Silacycles are ubiquitous building blocks. Small silacycles can typically be expanded catalytically. A silirane, silirene and phosphasilirene as well as a siletane and a silolene were prepared starting from the base-free bromosilylene [(dtbp Cbz)SiBr] (dtbp Cbz=1,8-bis(3,5-ditertbutylphenyl)-3,6-ditertbutylcarbazolyl). As these heterocycles were derived from a dicoordinated silylene, they are susceptible to reactions with an external base. The three-membered silacycles readily undergo non-catalysed ring expansion reactions with isonitriles yielding the related four-membered silacycles. Surprisingly, the ring-expanded derivatives of the silirane undergo up to two further isomerisation reactions, first by enamine formation and then by another ring expansion. DFT computations were utilised to gauge the scope of this reactivity pattern. Three-membered silacycles should essentially universally undergo a ring expansion with isonitriles, while for four-membered silacycles, only very few instances are predicted to accommodate more challenging kinetic requirements of this ring expansion. Larger silacycles lack the ring strain energy required for this ring expansion reaction and are not expected to be expanded.

Multi-site comparison of parametric T1 and T2 mapping: healthy travelling volunteers in the Berlin research network for cardiovascular magnetic resonance (BER-CMR).

BACKGROUND: Parametric mapping sequences in cardiovascular magnetic resonance (CMR) allow for non-invasive myocardial tissue characterization. However quantitative myocardial mapping is still limited by the need for local reference values. Confounders, such as field strength, vendors and sequences, make intersite comparisons challenging. This exploratory study aims to assess whether multi-site studies that control confounding factors provide first insights whether parametric mapping values are within pre-defined tolerance ranges across scanners and sites. METHODS: A cohort of 20 healthy travelling volunteers was prospectively scanned at three sites with a 3 T scanner from the same vendor using the same scanning protocol and acquisition scheme. A Modified Look-Locker inversion recovery sequence (MOLLI) for T1 and a fast low-angle shot sequence (FLASH) for T2 were used. At one site a scan-rescan was performed to assess the intra-scanner reproducibility. All acquired T1- and T2-mappings were analyzed in a core laboratory using the same post-processing approach and software. RESULTS: After exclusion of one volunteer due to an accidentally diagnosed cardiac disease, T1- and T2-maps of 19 volunteers showed no significant differences between the 3 T sites (mean ± SD [95% confidence interval] for global T1 in ms: site I: 1207 ± 32 [1192-1222]; site II: 1207 ± 40 [1184-1225]; site III: 1219 ± 26 [1207-1232]; p = 0.067; for global T2 in ms: site I: 40 ± 2 [39-41]; site II: 40 ± 1 [39-41]; site III 39 ± 2 [39-41]; p = 0.543). CONCLUSION: Parametric mapping results displayed initial hints at a sufficient similarity between sites when confounders, such as field strength, vendor diversity, acquisition schemes and post-processing analysis are harmonized. This finding needs to be confirmed in a powered clinical trial. Trial registration ISRCTN14627679 (retrospectively registered).

The illusion of stable fertility preferences.

Fertility preferences have long played a key role in models of fertility differentials and change. We examine the stability of preferences over time using rich panel data on Kenyan women's fertility desires, expectations, actual fertility, and recall of desires in three waves over a nine-year period, when respondents were in their 20s. We find that although desired fertility is quite unstable, most women perceive their desires to be stable. Under hypothetical future scenarios, few expect their desired fertility to increase over time but, in fact, such increases in fertility desires are common. Moreover, when asked to recall past desires, most respondents report previously wanting exactly as many children as they desire today. These patterns of bias are consistent with the emerging view that fertility desires are contextual, emotionally laden, and structured by identity.

Short-term results of the combined application of neodymium-doped yttrium aluminum garnet (Nd:YAG) laser and erbium-doped yttrium aluminum garnet (Er:YAG) laser in the treatment of periodontal disease: a randomized controlled trial.

OBJECTIVES: Nd:YAG and Er:YAG lasers have been previously used as an adjunct in periodontal therapy. The aim of this single-blinded randomized controlled clinical trial was to evaluate the efficacy of a combined application of Nd:YAG and Er:YAG laser irradiation in periodontal treatment. MATERIALS AND METHODS: Twenty-two patients with at least one site of ≥ 6 mm periodontal probing depth (PPD) after mechanical debridement with curettes and sonic instruments at periodontal reevaluation were included in the study. Patients were randomly allocated at a 1:1 ratio to either a combined Nd:YAG/Er:YAG laser therapy (test group) or a "turned off" laser therapy (control group). The Nd:YAG laser was used for periodontal pocket deepithelialization and to stabilize the resulting blood clot. The Er:YAG laser was primarily used for root surface modification. PPD (mm), clinical attachment level (CAL, mm), and bleeding on probing (BOP, +/-) at the site of laser treatment were evaluated at baseline and 2 months after treatment. RESULTS: The mean improvements from baseline to 2-month follow-up for PPD were significantly better in the laser group (2.05 ± 0.82 mm) compared to the control group (0.64 ± 0.90 mm; p = 0.001). Likewise, the gain in CAL was significantly better in the laser group (1.50 ± 1.10 mm) than in the control group (0.55 ± 1.01mm; p = 0.046). CONCLUSIONS: The combined application of Nd:YAG and Er:YAG laser irradiation as an adjunct to conventional non-surgical therapy showed a significant beneficial effect on periodontal treatment results. CLINICAL RELEVANCE: Combined Nd:YAG and Er:YAG laser irradiation could be a useful procedure additionally to conventional non-surgical periodontal therapy to improve periodontal treatment results. CLINICAL TRIAL REGISTRATION: ISRCTN registry #ISRCTN32132076.

Designer epigenome modifiers enable robust and sustained gene silencing in clinically relevant human cells.

Targeted modulation of gene expression represents a valuable approach to understand the mechanisms governing gene regulation. In a therapeutic context, it can be exploited to selectively modify the aberrant expression of a disease-causing gene or to provide the target cells with a new function. Here, we have established a novel platform for achieving precision epigenome editing using designer epigenome modifiers (DEMs). DEMs combine in a single molecule a DNA binding domain based on highly specific transcription activator-like effectors (TALEs) and several effector domains capable of inducing DNA methylation and locally altering the chromatin structure to silence target gene expression. We designed DEMs to target two human genes, CCR5 and CXCR4, with the aim of epigenetically silencing their expression in primary human T lymphocytes. We observed robust and sustained target gene silencing associated with reduced chromatin accessibility, increased promoter methylation at the target sites and undetectable changes in global gene expression. Our results demonstrate that DEMs can be successfully used to silence target gene expression in primary human cells with remarkably high specificity, paving the way for the establishment of a potential new class of therapeutics.

Streptococcus thermophilus CRISPR-Cas9 Systems Enable Specific Editing of the Human Genome.

RNA-guided nucleases (RGNs) based on the type II CRISPR-Cas9 system of Streptococcus pyogenes (Sp) have been widely used for genome editing in experimental models. However, the nontrivial level of off-target activity reported in several human cells may hamper clinical translation. RGN specificity depends on both the guide RNA (gRNA) and the protospacer adjacent motif (PAM) recognized by the Cas9 protein. We hypothesized that more stringent PAM requirements reduce the occurrence of off-target mutagenesis. To test this postulation, we generated RGNs based on two Streptococcus thermophilus (St) Cas9 proteins, which recognize longer PAMs, and performed a side-by-side comparison of the three RGN systems targeted to matching sites in two endogenous human loci, PRKDC and CARD11. Our results demonstrate that in samples with comparable on-target cleavage activities, significantly lower off-target mutagenesis was detected using St-based RGNs as compared to the standard Sp-RGNs. Moreover, similarly to SpCas9, the StCas9 proteins accepted truncated gRNAs, suggesting that the specificities of St-based RGNs can be further improved. In conclusion, our results show that Cas9 proteins with longer or more restrictive PAM requirements provide a safe alternative to SpCas9-based RGNs and hence a valuable option for future human gene therapy applications.

Outcomes in Cardiac Transthyretin Amyloidosis and Association With New York Heart Association Class: Real-World Data.

BACKGROUND: Results from ATTR-ACT (Safety and Efficacy of Tafamidis in Patients With Transthyretin Cardiomyopathy) indicate that tafamidis prolongs survival and reduces cardiovascular hospitalizations in cardiac transthyretin amyloidosis (ATTR-CA). However, real-world data supporting these findings are scarce. Thus, we sought to characterize the clinical outcome of patients with ATTR-CA treated with tafamidis in a real-world setting and assess the prognostic role of the New York Heart Association (NYHA) classification. METHODS AND RESULTS: We conducted a retrospective observational study, enrolling a consecutive sample of patients with ATTR-CA (wild-type or variant) treated with tafamidis. Clinical outcome was tracked through follow-up visits or phone calls. Primary outcomes were death and major adverse cardiac events (MACE), a composite end point of death and hospitalizations for acute cardiac decompensation, myocardial infarction, severe arrythmias, or stroke. Kaplan-Meier analysis estimated overall and MACE-free survival including NYHA subgroups (NYHA I/II versus NYHA III). One hundred sixty-seven patients with ATTR-CA (94.6% wild-type) were enrolled and followed for a median of 539 [323-869] days. Median overall survival was not reached. Estimated 1-year, 2-year, and 5-year overall survival among the whole cohort was 93.5%, 85.9%, and 70.2%, respectively. Overall survival was higher in the NYHA I/II subgroup (P=0.002). Median MACE-free survival time was 1082 (95% CI, 962-1202) days. MACE-free survival was higher in the NYHA I/II subgroup (P<0.001). With respective hazard ratios of 5.85 (95% CI, 1.48-23.18; P=0.012) and 3.95 (95% CI, 1.99-7.84; P<0.001), NYHA III was an independent predictor of death and MACE. CONCLUSIONS: Treatment of ATTR-CA with tafamidis led to substantial improvements of clinical outcome. NYHA classification at treatment initiation is a reliable tool to provide patients with individualized prognostic information.

Sex-specific structural and functional cardiac remodeling during healthy aging assessed by cardiovascular magnetic resonance.

BACKGROUND: Aging as a major non-modifiable cardiac risk factor challenges future cardiovascular medicine and economic demands, which requires further assessments addressing physiological age-associated cardiac changes. OBJECTIVES: Using cardiovascular magnetic resonance (CMR), this study aims to characterize sex-specific ventricular adaptations during healthy aging. METHODS: The population included healthy volunteers who underwent CMR at 1.5 or 3 Tesla scanners applying cine-imaging with a short-axis coverage of the left (LV) and right (RV) ventricle. The cohort was divided by sex (female and male) and age (subgroups in years): 1 (19-29), 2 (30-39), 3 (40-49), and 4 (≥50). Cardiac adaptations were quantitatively assessed by CMR indices. RESULTS: After the exclusion of missing or poor-quality CMR datasets or diagnosed disease, 140 of 203 volunteers were part of the final analysis. Women generally had smaller ventricular dimensions and LV mass, but higher biventricular systolic function. There was a significant age-associated decrease in ventricular dimensions as well as a significant increase in LV mass-to-volume ratio (LV-MVR, concentricity) in both sexes (LV-MVR in g/ml: age group 1 vs. 4: females 0.50 vs. 0.57, p=0.016, males 0.56 vs. 0.67, p=0.024). LV stroke volume index decreased significantly with age in both sexes, but stronger for men than for women (in ml/m2: age group 1 vs. 4: females 51.76 vs. 41.94, p<0.001, males 55.31 vs. 40.78, p<0.001). Ventricular proportions (RV-to-LV-volume ratio) were constant between the age groups in both sexes. CONCLUSIONS: In both sexes, healthy aging was associated with an increase in concentricity and a decline in ventricular dimensions. Furthermore, relevant age-related sex differences in systolic LV performance were observed.

A simplified approach to discriminate between healthy subjects and patients with heart failure using cardiac magnetic resonance myocardial deformation imaging.

Aims: Left ventricular global longitudinal strain (LV-GLS) shows promise as a marker to detect early heart failure (HF). This study sought to (i) establish cardiac magnetic resonance imaging (CMR)-derived LV-GLS cut-offs to differentiate healthy from HF for both acquisition-based and post-processing techniques, (ii) assess agreement, and (iii) provide a method to convert LV-GLS between both techniques. Methods and results: A secondary analysis of a prospective study enrolling healthy subjects (n = 19) and HF patients (n = 56) was conducted. LV-GLS was measured using fast strain-encoded imaging (fSENC) and feature tracking (FT). Receiver operating characteristic (ROC) analyses were performed to derive and evaluate LV-GLS cut-offs discriminating between healthy, HF with mild deformation impairment (DI), and HF with severe DI. Linear regression and Bland-Altman analyses assessed agreement. Cut-offs discriminating between healthy and HF were identified at -19.3% and -15.1% for fSENC and FT, respectively. Cut-offs of -15.8% (fSENC) and -10.8% (FT) further distinguished mild from severe DI. No significant differences in area under ROC curve were identified between fSENC and FT. Bland-Altman analysis revealed a bias of -4.01%, 95% CI -4.42, -3.50 for FT, considering fSENC as reference. Linear regression suggested a factor of 0.76 to rescale fSENC-derived LV-GLS to FT. Using this factor on fSENC-derived cut-offs yielded rescaled FT LV-GLS cut-offs of -14.7% (healthy vs. HF) and -12% (mild vs. severe DI). Conclusion: LV-GLS distinguishes healthy from HF with high accuracy. Each measurement technique requires distinct cut-offs, but rescaling factors facilitate conversion. An FT-based LV-GLS ≥ -15% simplifies HF detection in clinical routine.

The prognostic impact of human leukocyte antigen (HLA) class I antigen abnormalities in salivary gland cancer. A clinicopathological study of 288 cases.

AIMS: To study abnormalities of proteins of the major histocompatibility complex class I in a series of 288 salivary gland carcinomas, and to correlate findings with patients' overall survival (OS). METHODS AND RESULTS: Protein expression of human leukocyte antigen (HLA)-A, heavy chain (HC)-10, ß2 -microglobulin, low molecular weight polypeptides (LMP) 2 and 7, transporters associated with antigen processing (TAP) 1 and 2, calnexin, calreticulin, endoplasmic reticulum (ER) p57 and tapasin was evaluated by immunohistochemistry and semiquantitatively analyzed. As compared with normal salivary gland tissue, HLA-A, LMP7, TAP2 and HLA class I were significantly down-regulated in salivary gland carcinomas, whereas ß2 -microglobulin, calnexin, LMP2, and TAP1 were upregulated. Expression of calreticulin, ERp57 and tapasin was unaltered. In univariate Kaplan-Meier analyses, low expression of LMP7 (P = 0.005) and high expression of ß2 -microglobulin (P = 0.028), HLA-A (P < 0.001), TAP1 (P = 0.01), and tapasin (P < 0.001) were significantly associated with shorter OS. In multivariate analysis incorporating tumour stage, nodal/distant metastasis, and grade, HLA-A (P = 0.014), LMP7 (P = 0.033), and tapasin (P = 0.024), as well as distant metastasis (P = 0.012) and high tumour grade (P < 0.001), remained statistically significant. CONCLUSION: The prognostic influence of up-regulated HLA-A and tapasin and down-regulated LMP7 may provide a rationale for targeting these specific components of the antigen processing and presentation pathway in salivary gland carcinomas.

Cardiac sarcoidosis presenting with complex conduction abnormalities as the first manifestation of widespread systemic sarcoidosis: a case report.

Background: Sarcoidosis is a granulomatous multi-organ disease of unknown aetiology. Despite being relatively rare, cardiac sarcoidosis constitutes a very important manifestation of sarcoidosis, as its symptoms regularly precede or occur in isolation of more prevalent ones, and as it is the main driver of mortality in systemic sarcoidosis. Case summary: We present the case of a 37-year-old woman, in which clinically isolated cardiac sarcoidosis revealed widespread systemic sarcoidosis. Apart from constitutional symptoms and strong recurrent dizziness (i.e. near-syncopes), which persisted for multiple years already, our patient initially presented with complex conduction abnormalities, including a right bundle branch block, left anterior hemi-block, and atrioventricular block °1. Following inconclusive endomyocardial biopsies, performed due to detection of focal septal scarring on cardiac magnetic resonance imaging, an 18F-FDG-PET-CT, performed upon admission to our clinic, showed distinct hypermetabolic lesions indicative of active inflammation in various organs and raised suspicion of systemic sarcoidosis. Eventually, histopathological evidence of non-caseating granulomas in affected lymph nodes, extracted by bronchoscopy, confirmed the diagnosis of systemic sarcoidosis after reasonable exclusion of other granulomatous diseases. Immediate initiation of long-term immunosuppressive therapy led to almost complete remission, as monitored by consequential 18F-FDG-PET-CT scans. Discussion: Unexplained complex conduction abnormalities in young patients may be a sign of sarcoidosis, even in isolation of more prevalent symptoms. Correct interpretation and prompt initiation of a structured interdisciplinary diagnostic workup, including 18F-FDG-PET-CT as the imaging modality of choice, are essential to initiate specific treatment and obviate the major risk of mortality resulting from cardiac sarcoidosis.

Roadmap for phase change materials in photonics and beyond.

Phase Change Materials (PCMs) have demonstrated tremendous potential as a platform for achieving diverse functionalities in active and reconfigurable micro-nanophotonic devices across the electromagnetic spectrum, ranging from terahertz to visible frequencies. This comprehensive roadmap reviews the material and device aspects of PCMs, and their diverse applications in active and reconfigurable micro-nanophotonic devices across the electromagnetic spectrum. It discusses various device configurations and optimization techniques, including deep learning-based metasurface design. The integration of PCMs with Photonic Integrated Circuits and advanced electric-driven PCMs are explored. PCMs hold great promise for multifunctional device development, including applications in non-volatile memory, optical data storage, photonics, energy harvesting, biomedical technology, neuromorphic computing, thermal management, and flexible electronics.

Erratum: Roadmap for phase change materials in photonics and beyond.

[This corrects the article DOI: 10.1016/j.isci.2023.107946.].

The many faces of acinic cell carcinomas of the salivary glands: a study of 40 cases relating histological and immunohistological subtypes to clinical parameters and prognosis.

AIMS: To study the morphological heterogeneity of acinic cell carcinoma (ACC) in correlation with clinicopathological parameters. METHODS AND RESULTS: Forty well-characterized ACCs were classified as solid (n = 20), microcystic (n = 15), papillary-cystic (n = 4) or follicular (n = 1), based on the dominant architectural growth pattern. Fourteen tumours exhibited eosinophilic/clear cell morphology and 18 tumours were rich in zymogen granules (so-called blue dot tumours). High-grade morphology occurred in five tumours. Based on cytokeratin (CK) 7 staining and in analogy to CK7 expression in normal salivary gland epithelia, three distinct histogenetic subtypes were recognized: acinar (CK7-negative; n = 13), ductular (diffuse CK7-positive; n = 11) and mixed ductulo-acinar (10-66% CK7-positive cells; n = 16). Most papillary-cystic tumours displayed ductular differentiation (P = 0.015), whereas blue dot tumours never did (P < 0.001). Analysis of relapse-free survival (RFS) revealed that Stage I tumours had the best prognosis without any relapse in 18 years follow-up (P = 0.06). High-grade tumours were associated with shorter RFS (P = 0.028). Concerning the histogenetic types, monophasic (pure acinar or ductular) tumours were associated with a significantly better RFS than mixed ductulo-acinar tumours (P = 0.008). CONCLUSION: The results underscore the great histological diversity of ACC, and the value of histogenetic subtyping as an additional prognostic factor regarding RFS.

Highly tunable ß-relaxation enables the tailoring of crystallization in phase-change materials.

In glasses, secondary (ß-) relaxations are the predominant source of atomic dynamics. Recently, they have been discovered in covalently bonded glasses, i.e., amorphous phase-change materials (PCMs). However, it is unclear what the mechanism of ß-relaxations is in covalent systems and how they are related to crystallization behaviors of PCMs that are crucial properties for non-volatile memories and neuromorphic applications. Here we show direct evidence that crystallization is strongly linked to ß-relaxations. We find that the ß-relaxation in Ge15Sb85 possesses a high tunability, which enables a manipulation of crystallization kinetics by an order of magnitude. In-situ synchrotron X-ray scattering, dielectric functions, and ab-initio calculations indicate that the weakened ß-relaxation intensity stems from a local reinforcement of Peierls-like distortions, which increases the rigidity of the bonding network and decreases the dynamic heterogeneity. Our findings offer a conceptually new approach to tuning the crystallization of PCMs based on manipulating the ß-relaxations.

Salivary gland mucoepidermoid carcinoma is a clinically, morphologically and genetically heterogeneous entity: a clinicopathological study of 40 cases with emphasis on grading, histological variants and presence of the t(11;19) translocation.

AIMS: To correlate World Health Organization (WHO) grade, patient's outcome and presence of t(11;19) to histological tumour variants in 40 well-characterized mucoepidermoid carcinomas (MECs). METHODS AND RESULTS: MECs were classified as 'classical' based on the presence of equal proportions of the three cell types or the dominance (≥50%) of mucous cells together with at least one other cell type, and as 'variant' if composed of ≥80% of a single non-mucous cell type. Classical MECs were more common (n=23). Variant MECs had predominant squamoid (n=9), eosinophilic (n=5) or clear cell (n=3) morphology. Twenty-seven tumours were WHO grade 1, three grade 2 and ten grade 3. The t(11;19) was detected in 82%, 35% and 0% of classical MEC, variant MEC and non-MEC, respectively. Classical MECs were associated significantly with age ≤60 years (P<0.001), grade 1 (P<0.001) and t(11;19) (P=0.003). Short overall survival was associated significantly with age >60 years (P=0.001) and Union for International Cancer Control (UICC) stage >I (P=0.031), residual tumour (P<0.001), tumour grade >1 (P=0.001) and squamoid variant (P=0.002) in Kaplan-Meier analysis. CONCLUSIONS: The results underscore the great histological diversity of MEC, the reproducibility of the WHO grading criteria and the value of histological subtypes as an additional prognostic factor.