The use of pembrolizumab monotherapy for the management of head and neck squamous cell carcinoma (HNSCC) in the UK.

Pembrolizumab has received approval in the UK as first-line monotherapy for recurrent and/or metastatic HNSCC (R/M HNSCC) following the results of the KEYNOTE-048 trial, which demonstrated a longer overall survival (OS) in comparison to the EXTREME chemotherapy regimen in patients with a combined positive score (CPS) ≥1. In this article, we provide retrospective real-world data on the role of pembrolizumab monotherapy as first-line systemic therapy for HNSCC across 18 centers in the UK from March 20, 2020 to May 31, 2021. 211 patients were included, and in the efficacy analysis, the objective response rate (ORR) was 24.7%, the median progression-free survival (PFS) was 4.8 months (95% confidence interval [CI]: 3.6-6.1), and the median OS was 10.8 months (95% CI 9.0-12.5). Pembrolizumab monotherapy was well tolerated, with 18 patients having to stop treatment owing to immune-related adverse events (irAEs). 53 patients proceeded to second-line treatment with a median PFS2 of 10.2 months (95% CI: 8.8-11.5). Moreover, patients with documented irAEs had a statistically significant longer median PFS (11.3 vs. 3.3 months; log-rank p value = <.001) and median OS (18.8 vs. 8.9 months; log-rank p value <.001). The efficacy and safety of pembrolizumab first-line monotherapy for HNSCC has been validated using real-world data.

Neratinib could be effective as monotherapy or in combination with trastuzumab in HER2-low breast cancer cells and organoid models.

BACKGROUND: Previous studies have suggested that patients with HER2-low breast cancers do not benefit from trastuzumab treatment although the reasons remain unclear. METHODS: We investigated the effect of trastuzumab monotherapy and its combination with different HER2 targeting treatments in a panel of breast cancer cell lines and patient-derived organoids (PDOs) using biochemical methods and cell viability assays. RESULTS: Compared to sensitive HER2 over-expressing (IHC3 + ) breast cancer cells, increasing doses of trastuzumab could not achieve IC50 in MDA-MB-361 (IHC 2 + FISH + ) and MDA-MB-453 (IHC 2 + FISH-) cells which showed an intermediate response to trastuzumab. Trastuzumab treatment induced upregulation of HER ligand release, resulting in the activation of HER receptors in these cells, which could account for their trastuzumab insensitivity. Adding a dual ADAM10/17 inhibitor to inhibit the shedding of HER ligands in combination with trastuzumab only showed a modest decrease in the cell viability of HER2-low breast cancer cells and PDOs. However, the panHER inhibitor neratinib was an effective monotherapy in HER2-low breast cancer cells and PDOs, and showed additive effects when combined with trastuzumab. CONCLUSION: This study demonstrates that neratinib in combination with trastuzumab may be effective in a subset of HER2-low breast cancers although further validation is required in a larger panel of PDOs and in future clinical studies.

Concordance between ER, PR, Ki67, and HER2-low expression in breast cancer by MammaTyper RT-qPCR and immunohistochemistry: implications for the practising pathologist.

BACKGROUND: There are limited data on the role of multigene tests and their correlation with immunohistochemistry (IHC), especially on core biopsy. MammaTyper is a quantitative conformite Europeeanne (CE) marked, National Institute for Health and Care excellence (NICE) approved, in in vitro diagnostic quantitative real-time polymerase chain reaction (RT-qPCR) test for assessment of mRNA expression of four biomarkers (ESR1, PGR, ERBB2, MKI67). METHODS: We evaluated the concordance of MammaTyper with oestrogen receptor (ER), progesterone receptor (PR), HER2, and Ki67 by IHC on 133 core needle biopsies of breast cancer. HER2 was positive if IHC 3+ or 2+ and fluorescence in situ hybridization (FISH)-amplified. Global and hotspot Ki67 expression was analysed using a cutoff of ≥20% assessed manually and by digital image analysis. Agreements were expressed as overall percent agreement (OPA), positive percent agreement (PPA), negative percent agreement (NPA), and Cohen's kappa. RESULTS: RT-qPCR results of ESR1 were highly concordant with IHC with OPA of 94.7% using 1% cutoff and 91.7% when the low ER-positive category was included. The PPA and NPA between RT-qPCR and IHC for PR was 91.5% and 88.0%, respectively, when using the 1% cutoff. For ERBB2/HER2, the OPA was 95% and the PPA was 84.6%. 40 of 72 HER2 IHC score 0 tumours were classified as ERBB2 low. Best concordance between MKI67 by MammaTyper and Ki67 IHC was achieved using hotspot digital image analysis (OPA: 87.2%, PPA: 90.6%, NPA: 80%). CONCLUSION: RT-qPCR-based assessment of the mRNA expression of ESR1, PGR, ERBB2, and MKI67 showed high concordance with IHC, suggesting that the MammaTyper test on core needle biopsies represents a reliable, efficient, and reproducible alternative for breast cancer classification and refining HER2 low categorisation.

Implementing the time-to-event continual reassessment method in the presence of partial orders in a phase I head and neck cancer trial.

BACKGROUND: In this article we describe the methodology of the time-to-event continual reassessment method in the presence of partial orders (PO-TITE-CRM) and the process of implementing this trial design into a phase I trial in head and neck cancer called ADePT-DDR. The ADePT-DDR trial aims to find the maximum tolerated dose of an ATR inhibitor given in conjunction with radiotherapy in patients with head and neck squamous cell carcinoma. METHODS: The PO-TITE-CRM is a phase I trial design that builds upon the time-to-event continual reassessment method (TITE-CRM) to allow for the presence of partial ordering of doses. Partial orders occur in the case where the monotonicity assumption does not hold and the ordering of doses in terms of toxicity is not fully known. RESULTS: We arrived at a parameterisation of the design which performed well over a range of scenarios. Results from simulations were used iteratively to determine the best parameterisation of the design and we present the final set of simulations. We provide details on the methodology as well as insight into how it is applied to the trial. CONCLUSIONS: Whilst being a very efficient design we highlight some of the difficulties and challenges that come with implementing such a design. As the issue of partial ordering may become more frequent due to the increasing investigations of combination therapies we believe this account will be beneficial to those wishing to implement a design with partial orders. TRIAL REGISTRATION: ADePT-DDR was added to the European Clinical Trials Database (EudraCT number: 2020-001034-35) on 2020-08-07.

Clinical outcomes in relapsed oropharyngeal cancer after definitive (chemo) radiotherapy.

OBJECTIVES: To report clinical outcomes of relapsed oropharyngeal squamous cell carcinoma (OPSCC) after definitive intensity-modulated (chemo)radiotherapy [(C)RT]. MATERIALS AND METHODS: Data for all relapsed patients treated for OPSCC with definitive (C)RT between 2010 and 2016 were collected. Primary end-point was post-failure survival (PFS). RESULTS: Overall, 273 OPSCC patients completed definitive (C)RT. Of these, 42 cases (n = 26 human papilloma virus (HPV)-negative; n = 16 HPV-positive) had relapsed (n = 23 persistent disease; n = 19 recurrent disease) and were included in the final analysis. Two-year PFS for the entire population was 30.6%; 20.5% for HPV-negative and 43.8% for HPV-positive patients. Salvage curative surgery was associated with a significantly higher 2 years PFS rate (56.2%) compared with palliative treatment (22.9%) and best supportive care (0%) (p < 0.001). A positive trend in 2 years PFS was recorded in the early complete response cases (49.5%) versus patients who did not achieve a complete response within 3 months of the end of (C)RT (23.0%) (p = 0.11). CONCLUSION: A higher PFS rate is achieved when relapsed OPSCC cases are treated with salvage curative intent. HPV-positive disease and early complete response within 3 months from the end of (C)RT may be related to better PFS.

Local radiotherapy and E7 RNA-LPX vaccination show enhanced therapeutic efficacy in preclinical models of HPV16+ cancer.

Human papilloma virus (HPV) infection is a causative agent for several cancers types (genital, anal and head and neck region). The HPV E6 and E7 proteins are oncogenic drivers and thus are ideal candidates for therapeutic vaccination. We recently reported that a novel ribonucleic acid lipoplex (RNA-LPX)-based HPV16 vaccine, E7 RNA-LPX, mediates regression of mouse HPV16+ tumors and establishes protective T cell memory. An HPV16 E6/E7 RNA-LPX vaccine is currently being investigated in two phase I and II clinical trials in various HPV-driven cancer types; however, it remains a high unmet medical need for treatments for patients with radiosensitive HPV16+ tumors. Therefore, we set out to investigate the therapeutic efficacy of E7 RNA-LPX vaccine combined with standard-of-care local radiotherapy (LRT). We demonstrate that E7 RNA-LPX synergizes with LRT in HPV16+ mouse tumors, with potent therapeutic effects exceeding those of either monotherapy. Mode of action studies revealed that the E7 RNA-LPX vaccine induced high numbers of intratumoral-E7-specific CD8+ T cells, rendering cold tumors immunologically hot, whereas LRT primarily acted as a cytotoxic therapy, reducing tumor mass and intratumor hypoxia by predisposing tumor cells to antigen-specific T cell-mediated killing. Overall, LRT enhanced the effector function of E7 RNA-LPX-primed T cell responses. The therapeutic synergy was dependent on total radiation dose, rather than radiation dose-fractionation. Together, these results show that LRT synergizes with E7 RNA-LPX and enhances its anti-tumor activity against HPV16+ cancer models. This work paves into a new translational therapy for HPV16+ cancer patients.

Adaptation and validation of the main concept analysis of spoken discourse by native Japanese adults.

Many people with aphasia demonstrate problems of oral production at the discourse level. The Main Concept Analysis (MCA) for oral discourse production is a published evidence-based battery for quantifying the degree of presence, accuracy, completeness, and efficiency of targeted main concepts in oral discourse. In Japan, such a standardized tool specialized for assessing spoken discourse is currently lacking. The purpose of this study was to adapt the Japanese version of MCA for oral discourse production (the Japanese-MCA) and examine its validity and reliability. Stage 1 of the study involved the establishment of linguistically-specific main concepts (MCs) of the Japanese-MCA. Ten speech-language-hearing therapists and 60 healthy participants who were native monolingual Japanese speakers were recruited to determine MCs. Stage 2 examined the criterion validity and reliability of the Japanese-MCA. Language samples of 20 participants with aphasia, as verified by Standard Language Test of Aphasia (SLTA), and 20 healthy older participants were used. Results of Stage 1 of the study yielded normative data with a set of target MCs that were geographically and linguistically specific for use in Japan. The results also revealed the comparability of the Japanese-MCA and previously reported versions of other languages. Stage 2 findings indicated not only a high correlation of criterion validity, but also good reliability of the test. With established norms and specific scoring criteria of the Japanese-MCA, it is believed that this new tool will become a useful addition to clinical management and research of aphasia in Japan.

Sentence types and complexity of spontaneous discourse productions by Cantonese-speakers with traumatic brain injury- a preliminary report.

Previous investigations on sentence production in English-speaking individuals with traumatic brain injury (TBI) have yielded mixed conclusions based on their findings. While some studies found comparable sentence complexity between speakers with TBI and control speakers, others reported more syntactic and lexical errors, reduced sentence complexity, and erroneous word order transpositions in the sentence production of speakers with TBI. These contradictory findings could possibly be due to the use of language measures that were less sensitive to subtle syntactic impairments among speakers with TBI. In this preliminary report, the language samples obtained from 11 Cantonese-speaking participants with mild-moderate TBI in Guangzhou, with a mean age of 37.6 and mean years of education of 10 years, and nine control speakers with a similar age range and education background were analyzed using in-depth linguistic-oriented frameworks adopted from pervious works in Cantonese. The results indicated that the TBI group produced more errors, different varieties of sentence types, and lower syntactic complexity in their sentence production compared with the control group. The findings suggested that the more refined and linguistic-oriented measures used in the present study were more sensitive in identifying the subtle syntactic impairments produced by the participants with TBI.

WEE1 Inhibitor: Clinical Development.

PURPOSE OF REVIEW: WEE1 inhibitor has been shown to potential chemotherapy or radiotherapy sensitivity in preclinical models, particularly in p53-mutated or deficient cancer cells although not exclusively. Here, we review the clinical development of WEE1 inhibitor in combination with chemotherapy or radiotherapy with concurrent chemotherapy as well as its combination with different novel agents. RECENT FINDINGS: Although several clinical trials have shown that WEE1 inhibitor can be safely combined with different chemotherapy agents as well as radiotherapy with concurrent chemotherapy, its clinical development has been hampered by the higher rate of grade 3 toxicities when added to standard treatments. A few clinical trials had also been conducted to test WEE1 inhibitor using TP53 mutation as a predictive biomarker. However, TP53 mutation has not been shown to be the most reliable predictive biomarker and the benefit of adding WEE1 inhibitor to chemotherapy has been modest, even in TP53 biomarker-driven studies. There are ongoing clinical trials testing WEE1 inhibitor with novel agents such as ATR and PAPR inhibitors as well as anti-PDL1 immunotherapy, which may better define the role of WEE1 inhibitor in the future if any of the novel treatment combination will show superior anti-tumor efficacy with a good safety profile compared to monotherapy and/or standard treatment.

COVID-19 and Aphasia.

PURPOSE OF REVIEW: Aphasia is an acquired neurological language disorder after brain damages. Persons with aphasia (PWA) are more susceptible to behavioral and emotional implications due to inherent communication and/or cognitive difficulties. Currently, little is known regarding the impact of COVID-19 on PWA. RECENT FINDINGS: There are now growing reports with evidence of neurological and dysexecutive syndromes subsequent to interference of brain functions in acute patients with COVID-19, leading to variable aphasia-like symptoms. COVID-19 affected chronic PWA more in terms of disrupted communication and daily routines, worsened psychosocial well-being, and difficulties getting aphasia services that adequately addressed their needs. Acute versus chronic PWA were disproportionately affected by COVID-19. Recognizing, examining, and managing COVID-19-related neurological and behavioral problems in PWA is not straightforward. As we passed the 1-year mark and approaching the 2-year mark of the onset of COVID-19, more research is necessary to prioritize strategies for improving current evidence-based care and rehabilitation of aphasia.

Comprehensive Genomic and Transcriptomic Analysis of Three Synchronous Primary Tumours and a Recurrence from a Head and Neck Cancer Patient.

Synchronous primary malignancies occur in a small proportion of head and neck squamous cell carcinoma (HNSCC) patients. Here, we analysed three synchronous primaries and a recurrence from one patient by comparing the genomic and transcriptomic profiles among the tumour samples and determining the recurrence origin. We found remarkable levels of heterogeneity among the primary tumours, and through the patterns of shared mutations, we traced the origin of the recurrence. Interestingly, the patient carried germline variants that might have predisposed him to carcinogenesis, together with a history of alcohol and tobacco consumption. The mutational signature analysis confirmed the impact of alcohol exposure, with Signature 16 present in all tumour samples. Characterisation of immune cell infiltration highlighted an immunosuppressive environment in all samples, which exceeded the potential activity of T cells. Studies such as the one described here have important clinical value and contribute to personalised treatment decisions for patients with synchronous primaries and matched recurrences.

Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV): an open-label randomised controlled phase 3 trial.

BACKGROUND: The incidence of human papillomavirus (HPV)-positive oropharyngeal cancer, a disease affecting younger patients, is rapidly increasing. Cetuximab, an epidermal growth factor receptor inhibitor, has been proposed for treatment de-escalation in this setting to reduce the toxicity of standard cisplatin treatment, but no randomised evidence exists for the efficacy of this strategy. METHODS: We did an open-label randomised controlled phase 3 trial at 32 head and neck treatment centres in Ireland, the Netherlands, and the UK, in patients aged 18 years or older with HPV-positive low-risk oropharyngeal cancer (non-smokers or lifetime smokers with a smoking history of <10 pack-years). Eligible patients were randomly assigned (1:1) to receive, in addition to radiotherapy (70 Gy in 35 fractions), either intravenous cisplatin (100 mg/m2 on days 1, 22, and 43 of radiotherapy) or intravenous cetuximab (400 mg/m2 loading dose followed by seven weekly infusions of 250 mg/m2). The primary outcome was overall severe (grade 3-5) toxicity events at 24 months from the end of treatment. The primary outcome was assessed by intention-to-treat and per-protocol analyses. This trial is registered with the ISRCTN registry, number ISRCTN33522080. FINDINGS: Between Nov 12, 2012, and Oct 1, 2016, 334 patients were recruited (166 in the cisplatin group and 168 in the cetuximab group). Overall (acute and late) severe (grade 3-5) toxicity did not differ significantly between treatment groups at 24 months (mean number of events per patient 4·8 [95% CI 4·2-5·4] with cisplatin vs 4·8 [4·2-5·4] with cetuximab; p=0·98). At 24 months, overall all-grade toxicity did not differ significantly either (mean number of events per patient 29·2 [95% CI 27·3-31·0] with cisplatin vs 30·1 [28·3-31·9] with cetuximab; p=0·49). However, there was a significant difference between cisplatin and cetuximab in 2-year overall survival (97·5% vs 89·4%, hazard ratio 5·0 [95% CI 1·7-14·7]; p=0·001) and 2-year recurrence (6·0% vs 16·1%, 3·4 [1·6-7·2]; p=0·0007). INTERPRETATION: Compared with the standard cisplatin regimen, cetuximab showed no benefit in terms of reduced toxicity, but instead showed significant detriment in terms of tumour control. Cisplatin and radiotherapy should be used as the standard of care for HPV-positive low-risk patients who are able to tolerate cisplatin. FUNDING: Cancer Research UK.

Overcoming acquired resistance to HSP90 inhibition by targeting JAK-STAT signalling in triple-negative breast cancer.

BACKGROUND: Due to the lack of effective therapies and poor prognosis in TNBC (triple-negative breast cancer) patients, there is a strong need to develop effective novel targeted therapies for this subtype of breast cancer. Inhibition of heat shock protein 90 (HSP90), a conserved molecular chaperone that is involved in the regulation of oncogenic client proteins, has shown to be a promising therapeutic approach for TNBC. However, both intrinsic and acquired resistance to HSP90 inhibitors (HSP90i) limits their effectiveness in cancer patients. METHODS: We developed models of acquired resistance to HSP90i by prolonged exposure of TNBC cells to HSP90i (ganetespib) in vitro. Whole transcriptome profiling and a 328-compound bioactive small molecule screen were performed on these cells to identify the molecular basis of acquired resistance to HSP90i and potential therapeutic approaches to overcome resistance. RESULTS: Among a panel of seven TNBC cell lines, the most sensitive cell line (Hs578T) to HSP90i was selected as an in vitro model to investigate acquired resistance to HSP90i. Two independent HSP90i-resistant clones were successfully isolated which both showed absence of client proteins degradation, apoptosis induction and G2/M cell cycle arrest after treatment with HSP90i. Gene expression profiling and pathway enrichment analysis demonstrate significant activation of the survival JAK-STAT signalling pathway in both HSP90i-resistant clones, possibly through IL6 autocrine signalling. A bioactive small molecule screen also demonstrated that the HSP90i-resistant clones showed selective sensitivity to JAK2 inhibition. Inhibition of JAK and HSP90 caused higher induction of apoptosis, despite prior acquired resistance to HSP90i. CONCLUSIONS: Acquired resistance to HSP90i in TNBC cells is associated with an upregulated JAK-STAT signalling pathway. A combined inhibition of the JAK-STAT signalling pathway and HSP90 could overcome this resistance. The benefits of the combined therapy could be explored further for the development of effective targeted therapy in TNBC patients.

Cantonese AphasiaBank: An annotated database of spoken discourse and co-verbal gestures by healthy and language-impaired native Cantonese speakers.

This article reports the construction of a multimodal annotated database of spoken discourse and co-verbal gestures by native healthy speakers of Cantonese and individuals with language impairment: the Cantonese AphasiaBank. This corpus was established as a foundation for aphasiologists and clinicians to use in designing and conducting research investigations into theoretical and clinical issues related to acquired language disorders in Chinese. Details in terms of the purpose, structure, and levels of annotation of the database (containing part-of-speech-annotated orthographic transcripts with Romanization and the corresponding videos) are described. The discussion presents the challenges of building a spoken database of a language that is not linguistically well-researched and that does not have a standardized written form for many of its lexical items, as well as presenting how these issues were addressed. Most importantly, the article highlights the potential of Cantonese AphasiaBank as a powerful research tool for linguists and psycholinguists.

An analysis of topics and vocabulary in Chinese oral narratives by normal speakers and speakers with fluent aphasia.

This study analysed the topic and vocabulary of Chinese speakers based on language samples of personal recounts in a large spoken Chinese database recently made available in the public domain, i.e. Cantonese AphasiaBank ( http://www.speech.hku.hk/caphbank/search/ ). The goal of the analysis is to offer clinicians a rich source for selecting ecologically valid training materials for rehabilitating Chinese-speaking people with aphasia (PWA) in the design and planning of culturally and linguistically appropriate treatments. Discourse production of 65 Chinese-speaking PWA of fluent types (henceforth, PWFA) and their non-aphasic controls narrating an important event in their life were extracted from Cantonese AphasiaBank. Analyses of topics and vocabularies in terms of part-of-speech, word frequency, lexical semantics, and diversity were conducted. There was significant overlap in topics between the two groups. While the vocabulary was larger for controls than that of PWFA as expected, they were similar in distribution across parts-of-speech, frequency of occurrence, and the ratio of concrete to abstract items in major open word classes. Moreover, proportionately more different verbs than nouns were employed at the individual level for both speaker groups. The findings provide important implications for guiding directions of aphasia rehabilitation not only of fluent but also non-fluent Chinese aphasic speakers.

A Quantitative Study of Right Dislocation in Cantonese Spoken Discourse.

Right Dislocation (RD) has been suggested to be a focus marking device carrying an affective function motivated by limited planning time in conversation. The current study investigated the effects of genre type, planning load and affective function on the use of RD in Cantonese monologues. Discourse data were extracted from a recently developed corpus of oral narratives in Cantonese Chinese containing language samples from 144 native Cantonese speakers evenly distributed in age, education levels and gender. Three genre types representing different structures, styles and degrees of topic familiarity were chosen for an RD analysis: procedural description, story-telling and recount of personal event. The results revealed that genre types and planning load influenced the rate of RD occurrence. (1) Specifically, the lowest proportion of RD occurred in procedural description, assumed to be the most structured genre; whereas the highest rate was found in personal event recount, considered to be the most stylized and less structured genre. (2) The highest proportion of RD appeared near the end of a narrative, where heavier cognitive load is demanded compared with the beginning of a narrative; moreover, RD also tended to co-occur with disfluency. (3) There was a high percentage of RD tokens in the personal event recount for expressing explicit emotions; and (4) a lower rate of occurrence of RD was found in monologues than previous studies based on conversations. The overall findings suggest that the use of RD is sensitive to genre structure and style, as well as planning load effects.

A Taiwanese Mandarin Main Concept Analysis (TM-MCA) for quantification of aphasic oral discourse.

BACKGROUND: Various quantitative systems have been proposed to examine aphasic oral narratives in English. A clinical tool for assessing discourse produced by Cantonese-speaking persons with aphasia (PWA), namely Main Concept Analysis (MCA), was developed recently for quantifying the presence, accuracy and completeness of a narrative. Similar tools for Mandarin speakers are currently absent. AIMS: The first aim is to develop and establish the validity of the Taiwanese Mandarin Main Concept Analysis (TM-MCA) for the Mandarin-speaking population in Taiwan, given the paucity of related investigations. Another aim is to establish the influence of age and education level on Taiwanese Mandarin speakers' oral narrative abilities. The third purpose is to examine how well the TM-MCA could distinguish between native speakers with and without aphasia in Taiwan. The final aim is to examine the reliability and validity of the TM-MCA. METHODS & PROCEDURES: Eight speech-language pathologists (SLPs) and eight neurologically intact participants were involved to establish the TM-MCA main concepts. Another 36 neurologically intact participants and 10 PWA participated to validate the TM-MCA by contrasting their performance. OUTCOMES & RESULTS: Both age and educational level affected the oral discourse performance among the neurologically intact adults. Significant differences on the TM-MCA measures were noted between the control group and the group with aphasia. Moreover, the degree of aphasia significantly affected the oral discourse of PWA. CONCLUSIONS & IMPLICATIONS: The TM-MCA is a culturally appropriate quantitative system for the Taiwanese Mandarin population. It can be used to supplement standardized aphasia tests to help SLPs make more informative decisions not only on clinical diagnosis but also on treatment planning.

Students' perceptions of using Problem-Based Learning (PBL) in teaching cognitive communicative disorders.

Problem-Based Learning (PBL) is an educational model that is characterized by student-centered learning and classroom discussion using clinically based problems. This study examines students' perceptions of PBL as an alternative approach of learning in speech-language pathology and investigates if these perceptions change over time as a function of students' learning experience with PBL. Written reflections by 96 graduate-students in a graduate elective course on cognitive-communicative disorders were analyzed using content analysis. Common words or phrases in each reflection paper were identified, grouped and coded into consistent themes. Percentage changes of these themes across a semester were also followed. A total number of 883 positive and 165 negative comments were identified. Thirteen positive and seven negative themes relative to students' perception of the inclusion of PBL were yielded. The advantages of PBL were found to outweigh its disadvantages. Moreover, accumulated experience with this approach was found to eliminate some initial perceived drawbacks about PBL. The extra efforts to engage students in interactive discussion as well as higher order critical thinking and knowledge application were acknowledged through student feedback. Future studies should investigate how PBL can be of greater use in other areas in communication sciences and disorders.

AI and Aphasia in the Digital Age: A Critical Review.

Aphasiology has a long and rich tradition of contributing to understanding how culture, language, and social environment contribute to brain development and function. Recent breakthroughs in AI can transform the role of aphasiology in the digital age by leveraging speech data in all languages to model how damage to specific brain regions impacts linguistic universals such as grammar. These tools, including generative AI (ChatGPT) and natural language processing (NLP) models, could also inform practitioners working with clinical populations in the assessment and treatment of aphasia using AI-based interventions such as personalized therapy and adaptive platforms. Although these possibilities have generated enthusiasm in aphasiology, a rigorous interrogation of their limitations is necessary before AI is integrated into practice. We explain the history and first principles of reciprocity between AI and aphasiology, highlighting how lesioning neural networks opened the black box of cognitive neurolinguistic processing. We then argue that when more data from aphasia across languages become digitized and available online, deep learning will reveal hitherto unreported patterns of language processing of theoretical interest for aphasiologists. We also anticipate some problems using AI, including language biases, cultural, ethical, and scientific limitations, a misrepresentation of marginalized languages, and a lack of rigorous validation of tools. However, as these challenges are met with better governance, AI could have an equitable impact.