Uncovering the potential for a weakly supervised end-to-end model in recognising speech from patient with post-stroke aphasia

Post-stroke speech and language deficits (aphasia) significantly impact patients' quality of life. Many with mild symptoms remain undiagnosed, and the majority do not receive the intensive doses of therapy recommended, due to healthcare costs and/or inadequate services. Automatic Speech Recognition (ASR) may help overcome these difficulties by improving diagnostic rates and providing feedback during tailored therapy. However, its performance is often unsatisfactory due to the high variability in speech errors and scarcity of training datasets. This study assessed the performance of Whisper, a recently released end-to-end model, in patients with post-stroke aphasia (PWA). We tuned its hyperparameters to achieve the lowest word error rate (WER) on aphasic speech. WER was significantly higher in PWA compared to age-matched controls (10.3% vs 38.5%, p < 0.001). We demonstrated that worse WER was related to the more severe aphasia as measured by expressive (overt naming, and spontaneous speech production) and receptive (written and spoken comprehension) language assessments. Stroke lesion size did not affect the performance of Whisper. Linear mixed models accounting for demographic factors, therapy duration, and time since stroke, confirmed worse Whisper performance with left hemispheric frontal lesions. We discuss the implications of these findings for how future ASR can be improved in PWA

Mitochondrial caseinolytic protease p: A possible novel prognostic marker and therapeutic target in cancer

Caseinolytic protease P (ClpP) is a mitochondrial serine protease. In mammalian cells, the heterodimerization of ClpP and its AAA+ ClpX chaperone results in a complex called ClpXP, which has a relevant role in protein homeostasis and in maintaining mitochondrial functionality through the degradation of mitochondrial misfolded or damaged proteins. Recent studies demonstrate that ClpP is upregulated in primary and metastatic human tumors, supports tumor cell proliferation, and its overexpression desensitizes cells to cisplatin. Interestingly, small modulators of ClpP activity, both activators and inhibitors, are able to impair oxidative phosphorylation in cancer cells and to induce apoptosis. This review provides an overview of the role of ClpP in regulating mitochondrial functionality, in supporting tumor cell proliferation and cisplatin resistance; finally, we discuss whether this protease could represent a new prognostic marker and therapeutic target for the treatment of cancer

Metaplasia ossea diagnosticata su leiomioma uterino

Riportiamo un caso di metaplasia ossea in un leiomioma uterino scoperto casualmente in una donna di 53 anni operata di isterectomia totale per una neoformazione annessial

Lymph node metastases displaying lower Ki-67 immunostaining activity than the primary breast cancer

The aim of the study was to verify by Ki-67 immunostaining if any difference exists in the cell proliferating fraction between primary breast tumors (PTs) and matching positive axillary lymph nodes (ALNs). PATIENTS AND METHODS: Immunohistochemistry with the monoclonal antibody against Ki-67 was performed in 160 node-positive breast carcinomas and in their respective lymph node metastases. RESULTS: An increase of Ki-67 immunoreactive cells in ALN compared with that of PTs was observed in 84% of cases (ALN: mean 17%, PTs: mean 8%; p < 0.001), whereas 16% of the cases showed Ki-67 value two to six times lower in the ALNs than in the corresponding PTs (ALN: mean 3.2%, PTs mean 12.5%; p < 0.005). The decrease of Ki-67 positive cells in the ALN was independent from the histotype and the histological grade of the tumor. CONCLUSION: A different cell proliferation fraction between PTs and matching positive ALNs was demonstrated and underlined that the existence of a group of patients with decreased number of Ki-67 immunoreactive cells in lymph node metastases compared with that of the primary tumors could be taken into account in the choice of therapeutic strategy

Effects of Ti6Al4V mechanical and thermal surface modification on the adhesion of a chitosan-bioactive glass coating

Biomedical implants interact with human tissues introducing significant perturbation into the body. Implant surfaces can be then functionalized enabling better biocompatibility. At the same time, the additional use of a coating provides further functions such as corrosion protection, osteointegration, and drug delivery. In this context, a composite made of chitosan and bioactive glass nanoparticles has been used for coating Ti6Al4V alloy samples processed beforehand using different processes, i.e., polishing, milling, grit blasting, and electrical discharge machining. Experiments have been carried out to correlate substrate surface conditions and coating effectiveness in terms of scratch resistance with the final aim to obtain suitable guidelines to improve substrate-coating performances

Clinical relevance of thymidylate syntetase expression in the signet ring cell histotype component of colorectal carcinoma

Thymidylate Synthase (TS) is the key enzyme for DNA synthesis pathways and is inhibited by 5-fluorouracil (5FU). The aim of this work was to study TS expression and the proliferation rate in the different histological types of colorectal carcinoma (CRC). 50 patients with CRC were included in this study and evaluated immunohistochemically using the monoclonal antibodies, TS106 and Ki67. 20 tumours were of the intestinal type, 15 cases were signet ring cell carcinoma (SRCCs) and 15 cases were "mixed-type", with at least two different histological components. Intestinal and mucinous histotypes were positive for TS and Ki67, while "signet ring cell" samples were negative or showed only weak and focal positivity for both the TS and Ki67 antibodies. Our results show that signet ring cells (that are also often present in intestinal and mucinous carcinomas), are in the post-mitotic phase of the cell cycle and show a low proliferation index and TS expression. As TS is the key enzyme for DNA synthesis pathways and is inhibited by 5-fluorouracil (5FU), we can hypothesise that TS expression levels in the different histotypes of CRC could affect the potential responsiveness of these tumours to fluoropyrimidine chemotherapy, with a low efficacy being expected in signet ring cell areas

A Troubling Diagnosis of Verrucous Squamous Cell Carcinoma (“the Bad Kind” of Keratosis) and the Need of Clinical and Pathological Correlations: A Review of the Literature with a Case Report

Verrucous carcinoma (also known as Ackerman tumor) is an uncommon exophytic low-grade well-differentiated variant of squamous cell carcinoma. This neoplasm typically involves the oral cavity, larynx, genitalia, skin, and esophagus. It is well known for its locally aggressiveness and for its clinically slow-growing behaviour with minimal metastatic potential. Verrucous carcinoma of oral cavity is so closely aligned with the use of snuff and chewing tobacco that it has been called the “snuff dipper's cancer”. Recent studies have proved the role of HPV. The typical clinical presentation of oral verrucous carcinoma has long been known, as its remarkably innocuous appearance and biological behaviour. In this work, we report a review of the scientific literature and describe a troublesome case of oral verrucous cancer

The effect of CYP3A5 and ABCB1 single nucleotide polymorphisms on tacrolimus dose requirements in Caucasian liver transplant patients

Background: Tacrolimus is a substrate of cytochrome P-450 (CYP) 3A enzyme and of the drug transporter ABCBl. We have investigated the effects of possible relevant CYP3A5 and ABCBl single nucleotide polymorphisms (SNPs) present in both donors and recipients on tacrolimus blood levels achieved in a population of 32 Caucasian liver transplant patients. Material/Methods: At 1, 3 and 6 months after transplantation, tacrolimus doses (mg/kg/day) and trough blood levels (C0) were determined. Polymerase chain reaction followed by restriction fragment length polymorphism analysis was used for gen-otyping CYP3A5*3 [6986A&gt;G] as well as ABCBl at exons 21 [2677G&gt;T] and 26 [3435C&gt;T]. Results:87.5% of the population showed a CYP3A5*3/*3 genotype. For the ABCBl SNPs, in the case of 3435C&gt;T the total frequency observed for the allelic variant was 50%. For the 2677G&gt;T, the total frequency of the allelic variant was 12.5%, lower than in other Caucasian populations and without any significant linkage with 3435C&gt;T. At 3 and 6 months after transplantation, tacrolimus dose requirements were significantly higher in patients receiving a liver with one copy of the *1 al-lele compared to those homozygous for the *3 allele (0.111±0.057 vs. 0.057±0.030 [P&lt;0.05] at 3 month and 0.086±0.051 vs. 0.044±0.025 [P&lt;0.05] at 6 month). For the recipients' genotypes, the presence of at least one *1 copy tended, though not statistically significantly, to increase tacrolimus doses. With regard to the ABCBl SNPs, they did not show any influence on tacrolimus dosing requirements. Conclusions: Pharmacogenetic analysis of CYP3A5 in the donor could contribute to determine the appropriate initial dosage of tacrolimus in liver transplant patient

Prostate cancer biomarkers: a practical review based on different clinical scenarios

Traditionally, diagnosis and staging of prostate cancer (PCa) have been based on prostate-specific antigen (PSA) level, digital rectal examination (DRE), and transrectal ultrasound (TRUS) guided prostate biopsy. Biomarkers have been introduced into clinical practice to reduce the overdiagnosis and overtreatment of low-grade PCa and increase the success of personalized therapies for high-grade and high-stage PCa. The purpose of this review was to describe available PCa biomarkers and examine their use in clinical practice. A nonsystematic literature review was performed using PubMed and Scopus to retrieve papers related to PCa biomarkers. In addition, we manually searched websites of major urological associations for PCa guidelines to evaluate available evidence and recommendations on the role of biomarkers and their potential contribution to PCa decision-making. In addition to PSA and its derivates, thirteen blood, urine, and tissue biomarkers are mentioned in various PCa guidelines. Retrospective studies have shown their utility in three main clinical scenarios: (1) deciding whether to perform a biopsy, (2) distinguishing patients who require active treatment from those who can benefit from active surveillance, and (3) defining a subset of high-risk PCa patients who can benefit from additional therapies after RP. Several validated PCa biomarkers have become commercially available in recent years. Guidelines now recommend offering these tests in situations in which the assay result, when considered in combination with routine clinical factors, is likely to affect management. However, the lack of direct comparisons and the unproven benefits, in terms of long-term survival and cost-effectiveness, prevent these biomarkers from being integrated into routine clinical use