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Aneurysmal bone cysts (ABCs) are benign bone tumors typically affecting children. Mandibular ABCs can be difficult to treat surgically, given their sensitive anatomic location and functional and cosmetic impacts. This report presents 3 pediatric patients with mandibular ABCs successfully treated with image-guided percutaneous doxycycline sclerotherapy. The first 2 patients presented with pain and swelling, whereas the third was diagnosed incidentally. Sclerotherapy was the sole treatment for cases 1 and 2, whereas case 3 had sclerotherapy after recurrence following prior surgeries. In all 3 patients, clinical symptoms resolved, and stable bone healing was documented on long-term follow-up. There were no functional or cosmetic complications. Doxycycline sclerotherapy is a safe and viable treatment for primary and recurrent mandibular ABCs., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of Mutaz B. Habal, MD.)

Purpose: To evaluate the safety, effectiveness, and patient satisfaction of doxycycline sclerotherapy for aneurysmal bone cysts (ABCs) and unicameral bone cysts (UBCs)., Materials and Methods: This was an institutional review board (IRB)-approved single-center retrospective review of all ABCs and UBCs of the appendicular skeleton and pelvis completing doxycycline sclerotherapy and having at least 2 years of follow-up from 2007 to 2021. Radiographic outcomes in a patient cohort were assessed with a modified Neer score. Patient-reported outcome (PRO) surveys were completed by a subgroup of the cohort assessing pain after treatment (Likert scale), functional outcomes (Patient-Reported Outcomes Measurement Information System), and overall patient satisfaction (adapted from the Musculoskeletal Tumor Society)., Results: Seventy-seven lesions met the inclusion criteria, with 55 (71%) receiving bone void filler in addition to doxycycline. Of the 77 lesions, 76 (99%) were successfully treated. Twelve lesions (16%) recurred but resolved with additional doxycycline treatment. One lesion failed sclerotherapy, requiring surgical excision. Of the 383 total treatments performed, 17 resulted in Society of Interventional Radiology (SIR)-classified adverse events (9 with Grade 1, 7 with Grade 2, and 1 with Grade 3). Twenty-five (32%) of the 77 cases completed PRO surveys, with 20 (80%) having little to no pain and 15 (60%) having no functional impairment after completing treatment. The PRO surveys documented high levels of satisfaction, with all patients agreeing that they would undergo doxycycline sclerotherapy again if given the option., Conclusions: Doxycycline sclerotherapy (with or without bone void filler) is a safe, effective, and well-tolerated stand-alone treatment for ABCs and UBCs., (Copyright © 2024 SIR. Published by Elsevier Inc. All rights reserved.)

Purpose: The assessment and diagnosis of apraxia of speech (AOS) have been well studied in the English context, yet there is limited understanding of the clinical practice in speakers of other languages, like Cantonese. This study aimed to obtain information about the clinical practice of assessment methods and diagnostic criteria used, and confidence in diagnosing, AOS in Cantonese speakers., Method: An online survey constructed with Google Forms was completed by 27 speech-language pathologists (SLPs) in Hong Kong. The questionnaire comprised 12 questions covering (a) demographic information, (b) experience working with speakers with AOS, (c) confidence in making AOS diagnosis in Cantonese speakers, (d) assessment tasks or methods used for assessing AOS in Cantonese speakers, (e) clinical features used for diagnostic purposes, and (f) assessment tasks used to determine the presence of clinical features for diagnostic purposes., Result: All respondents (100%) made AOS diagnoses based on the observed clinical features, while no respondents made diagnoses using only standardised tests or quantitative measures. Six clinical features were commonly used by most of the respondents: articulatory groping (100%), inconsistent articulatory errors (100%), length effects (85.2%), difficulty initiating speech (81.5%), automaticity effects (81.5%), and sound distortions (77.8%). More than half of the respondents collected connected speech samples (64%), and conducted diadochokinesis (64%) and repetition tasks (64%). The average confidence level of the respondents for making AOS diagnoses was fair (3.63/5)., Conclusion: The SLPs in Hong Kong make AOS diagnoses based on the observed clinical features that have been reported in the English literature. Although some of the clinical features have been updated as non-discriminatory for AOS, they are still being used for AOS diagnosis in Cantonese speakers. Tendencies were observed with respect to the assessment tasks selected. The fair diagnostic confidence level suggests a need for future investigations of AOS in Cantonese speakers and the development of assessment tools.

Summary: Transcript quantification tools efficiently map bulk RNA sequencing (RNA-seq) reads to reference transcriptomes. However, their output consists of transcript count estimates that are subject to multiple biases and cannot be readily used with existing differential gene expression analysis tools in Python.Here we present pytximport, a Python implementation of the tximport R package that supports a variety of input formats, different modes of bias correction, inferential replicates, gene-level summarization of transcript counts, transcript-level exports, transcript-to-gene mapping generation, and optional filtering of transcripts by biotype. pytximport is part of the scverse ecosystem of open-source Python software packages for omics analyses and includes both a Python as well as a command-line interface.With pytximport, we propose a bulk RNA-seq analysis workflow based on Bioconda and scverse ecosystem packages, ensuring reproducible analyses through Snakemake rules. We apply this pipeline to a publicly available RNA-seq dataset, demonstrating how pytximport enables the creation of Python-centric workflows capable of providing insights into transcriptomic alterations., Availability and Implementation: pytximport is licensed under the GNU General Public License version 3. The source code is available at https://github.com/complextissue/pytximport and via Zenodo with DOI: 10.5281/zenodo.13907917. A related Snakemake workflow is available through GitHub at https://github.com/complextissue/snakemake-bulk-rna-seq-workflow and Zenodo with DOI: 10.5281/zenodo.12713811. Documentation and a vignette for new users are available at: https://pytximport.readthedocs.io., (© The Author(s) 2024. Published by Oxford University Press.)

Purpose: Pitch variations (tone productions) have been reported as a measure to differentiate Cantonese-speaking children with and without childhood apraxia of speech (CAS). This study aims to examine fundamental frequency ( F 0) changes within syllables and the effects of syllable structure, lexical status, and syllable positions on F 0 in Cantonese-speaking preschool children with and without CAS., Method: Six children with CAS, six children with non-CAS speech sound disorder plus language disorder (S&LD), 22 children with speech sound disorder only (SSD), and 63 children with typical speech-language development (TD) performed the tone sequencing task (TST). Growth curve analysis was employed to analyze and compare the F 0 values within syllables with three Cantonese tones (high level, high rising, and low falling). The analysis considered the effects of syllable structure (vowel and consonant-vowel), lexical status (word and nonword), and syllable position (initial, medial, and final) on F 0, as well as comparisons within and between groups., Results: Within each group, the effects of syllable structure and position on F 0 values were found with different patterns. Between-group comparisons showed that the CAS group had reduced F 0 contrasts. The CAS group could be differentiated from the control groups based on interactions of F 0 with syllable structure and position, but not lexical status. The dissimilarity of F 0 values detected between the CAS and SSD/TD groups was more prominent than that observed between the CAS and S&LD groups., Conclusions: This study demonstrated that Cantonese-speaking children with CAS had difficulty in varying F 0 within syllables as compared to those without CAS, suggesting pitch variation difficulty and language-specific impairment profiles in CAS. Future investigations of objective measures for identifying Cantonese speakers with CAS and cross-linguistic investigations using growth curve analysis and the TST are suggested.

Macrophages are functionally heterogeneous cells essential for apoptotic cell clearance. Apoptotic cells are defined by homogeneous characteristics, ignoring their original cell lineage identity. We found that in an interleukin-4 (IL-4)-enriched environment, the sensing of apoptotic neutrophils by macrophages triggered their tissue remodeling signature. Engulfment of apoptotic hepatocytes promoted a tolerogenic phenotype, whereas phagocytosis of T cells had little effect on IL-4-induced gene expression. In a mouse model of parasite-induced pathology, the transfer of macrophages conditioned with IL-4 and apoptotic neutrophils promoted parasitic egg clearance. Knockout of phagocytic receptors required for the uptake of apoptotic neutrophils and partially T cells, but not hepatocytes, exacerbated helminth infection. These findings suggest that the identity of apoptotic cells may contribute to the development of distinct IL-4-driven immune programs in macrophages.

Purpose: Literature on apraxia of speech (AOS) in Chinese speakers is sparse compared to the English literature. This study aims to examine the pitch variation skills of Cantonese adults with AOS poststroke in terms of perceptual tone accuracy, acoustic fundamental frequency ( f o ) changes, and repetition durations on items with different syllable structures, lexical status, and tone syllables in various positions in a sequencing context., Method: Six Cantonese adults with AOS poststroke (AOS group), six adults without AOS poststroke (nAOS group), and six healthy controls (HC group) performed the tone sequencing task (TST), which was adapted from oral diadochokinetic tasks, with three different tone syllables. Tone accuracy, f o values across 10 time points, and acoustic repetition durations were compared within and between the groups., Results: The AOS group produced significantly lower tone accuracy and different f o changes on the three Cantonese tone syllables compared with the control groups and significantly longer repetition durations than the HC group. The AOS group showed more difficulty with the tone syllables with the consonant-vowel structure, while a priming effect was observed on the T2 (high-rising) syllables with lexical meanings. A unique lowering of f o in the final syllable of the trisyllabic items was observed only in the AOS group., Conclusions: The AOS group showed degraded pitch variation skills. The effects of the three linguistic elements were discussed. Future investigations are called for to adapt the TST in other tonal languages to determine if degraded pitch variation skills are present in other tonal language speakers with AOS.

Background: The International Classification of Functioning, Disability, and Health (ICF) model has been applied in post-stroke rehabilitation, yet limited studies explored its clinical application on enhancing patients' Activity and Participation (ICF-A&P) level., Purpose: This study gathered evidence of the effects of an ICF-based post-stroke rehabilitation program (ICF-PSRP) in enhancing community reintegration in terms of ICF-A&P of post-stroke patients., Methods: Fifty-two post-stroke patients completed an 8 to 12 weeks multidisciplinary ICF-PSRP after setting personal treatment goals in an outpatient community rehabilitation center. Intake and pre-discharge assessments were administered for primary outcomes of Body function (ICF-BF; e.g., muscle strength) and ICF-A&P (e.g., mobility), and secondary outcomes of perceived improvements in ability (e.g., goal attainment and quality of life)., Results: There were significantly higher levels in the ICF-BF and ICF-A&P domains, except cognitive function under the ICF-BF. Improvements in the primary outcomes predicted corresponding secondary outcomes. Firstly, expressive and receptive functions (ICP-BF) were mediated by the everyday language (ICF-A&P) which predicted patients' satisfaction with the language-related quality of life. Secondly, upper extremity function (ICP-BF) was mediated by the lower extremity mobility (ICF-A&P) predicting work and productivity-related quality of life. Content analyses showed that combined ICF-BF and ICF-A&P contents throughout the ICF-PSRP contributed to the positive treatment effects., Conclusion: The ICF-PSRP was effective in promoting body function, and activity and participation levels of post-stroke patients. Positive treatment effects are characterized by goal-setting process, cross-domain content design, and community-setting delivery. Clinical trial registration : https://clinicaltrials.gov/study/NCT05941078?id=NCT05941078&rank=1, identifier NCT05941078., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wong, Cheung, Ng, Yuan, Lam, Fu and Chan.)

Background: Body functions and structures, activities, and participation are the core components in the International Classification of Functioning, Disability, and Health (ICF) to identify post-stroke patients' health conditions. The specification of health conditions enhances the outcomes of post-stroke rehabilitation., Purpose: This study aimed to explore the extent and the processes in an ICF-based post-stroke rehabilitation program (ICF-PSRP) that could enhance patients' community reintegration level., Methods: Post-stroke patients who completed the ICF-PSRP participated in intake and pre-discharge individual face-to-face semi-structured interviews. In addition, case therapists were invited to a face-to-face semi-structured group interview. Clinician experts were invited to complete an interview with the same interview contents as case therapists but in an online format. All interview recordings were analyzed with the Framework analysis. Patients' treatment goals were mapped with the ICF Core Set for Stroke., Results: Out of 37 invited post-stroke patients, thirty-three of them completed the interview. Three case therapists and five clinicians completed the interviews. The goals set by the patients and their caregivers showed a broadening of their scope over the course of the program. The changes in scope ranged from the activities to the participation and environmental components. Increases in patient-therapist interactions played an essential role in the goal-setting process, which were integral to personalizing the treatment content. These characteristics were perceived by all parties who contributed to the program outcomes., Conclusion: The application of ICF's principles and core components offers a useful framework for enhancing post-stroke patients' community reintegration level. Future studies should explore the way in which patient-therapist interaction, exposure to environmental factors, and personalized interventions maximize the benefits of applying this framework to the community integration of post-stroke patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Wong, Tong, Cheung, Ng, Yuan, Lam, Fu and Chan.)

The 3 rd -7 th edition of the American Joint Committee on Cancer had 3 categories for positive lymph nodes (pN1-3) in upper urinary tract carcinomas. The 8th edition removed pN3, defining pN1 as one lymph node with a tumor deposit ≤2 cm and pN2 as a node with a tumor deposit >2 cm or metastases in multiple nodes. The aim of this study was to assess if the current pN categories impact survival in renal pelvic and ureteral carcinomas. Nephroureterectomies performed at our institution for primary upper urinary tract carcinomas between 2010 and 2019 were reviewed. Lymphadenectomy was performed in 73.3% of cases (151/206, median = 9 nodes). Eighty-one (53.6%) patients were deceased at the last review (pN0, 53 [44.5%]; pN1-2, 28 [87.5%]). There was no difference in overall or recurrence-free survival between pN1 and pN2 with 5-year overall survival (95% confidence interval) of pN0, 60.7% (52.0-70.8%); pN1, 15.4% (4.3-35.2%); and pN2, 21.1% (8.8-40.3%). The metastatic deposit size threshold of 2 cm, the number of positive lymph nodes, as well as extranodal extension did not correlate with overall or recurrence-free survival. As such, pN1 and pN2 were grouped together with a 5-year overall survival of 18.8% (9.12-28.6%). The current stratification of upper urinary tract carcinomas into pN1 and pN2 does not provide prognostic information, and both yield a stage IV classification, regardless of pT or pM category. Therefore, we recommend further simplification of pN classification into one category for regional lymph node metastasis, irrespective of the lymph node deposit size or number of positive lymph nodes., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Previous studies have identified a unique Treg population, which expresses the Th17 characteristic transcription factor RORγt. These RORγt + Tregs possess enhanced immunosuppressive capacity, which endows them with great therapeutic potential. However, as a caveat, they are also capable of secreting pro-inflammatory IL-17A. Since the sum function of RORγt + Tregs in glomerulonephritis (GN) remains unknown, we studied the effects of their absence. Purified CD4 + T cell populations, containing or lacking RORγt + Tregs, were transferred into immunocompromised RAG1 knockout mice and the nephrotoxic nephritis model of GN was induced. Absence of RORγt + Tregs significantly aggravated kidney injury, demonstrating overall kidney-protective properties. Analyses of immune responses showed that RORγt + Tregs were broadly immunosuppressive with no preference for a particular type of T cell response. Further characterization revealed a distinct functional and transcriptional profile, including enhanced production of IL-10. Expression of the chemokine receptor CCR6 marked a particularly potent subset, whose absence significantly worsened GN. As an underlying mechanism, we found that chemokine CCL20 acting through receptor CCR6 signaling mediated expansion and activation of RORγt + Tregs. Finally, we also detected an increase of CCR6 + Tregs in kidney biopsies, as well as enhanced secretion of chemokine CCL20 in 21 patients with anti-neutrophil cytoplasmic antibody associated GN compared to that of 31 healthy living donors, indicating clinical relevance. Thus, our data characterize RORγt + Tregs as anti-inflammatory mediators of GN and identify them as promising target for Treg directed therapies., (Copyright © 2023 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Childhood apraxia of speech (CAS) is a paediatric motor speech disorder. We investigated the lexical tone perception and production abilities of children with CAS and the relationships between the two. Three children with CAS, aged between 3;7 and 5;8, were given the Cantonese Tone Identification Test (CANTIT) and the Hong Kong Cantonese Articulation Test (HKCAT) for assessment of tone perception and production, respectively. Accuracy and error patterns were investigated based on their performance on the two tests. Correlation analysis was performed on children's perception and production scores. Two children scored at the lowest rank on the CANTIT, while one child obtained a Z score of 0. All children scored three standard deviations below the mean on the HKCAT. No statistical differences were found among the six tones with respect to perception accuracy, H (5) = 3.731, p = 0.589. Error analysis showed that children with CAS demonstrated more confusion on perceiving tones compared with TD peers. There were no main effects for task ( F (1,2) = 0.040, p = 0.859) or tone (F(5,10 = 0.997, p = 0.467); nor were there task or tone interaction effects on perception versus production accuracy ( F (5,10) = 1.772, p = 0.206). Tone perception and production accuracy were not significantly correlated ( r 2  = 0.181, p = 0.078). Tone perception deficits were evident in two out of three children with CAS, while all children had lexical tone production difficulties. In this small sample, tone production was more universally affected than tone perception.

The problem in language comprehension in people with right hemisphere damage (RHD) is more equivocal than people with left hemisphere damage. This study explores the reading and listening comprehension of Cantonese-speaking individuals with RHD, left hemisphere damage, and neurotypical healthy controls using the Cantonese Computerized Revised Token Test (CRTT-Cantonese) adapted from the English CRTT. Eighteen native Cantonese-speaking individuals with RHD, 32 individuals with left hemisphere damage and aphasia (PWA), and 42 healthy controls participated in this study. All the participants completed the Cantonese Aphasia Battery, Hong Kong Oxford Cognitive Screen, the listening comprehension version of CRTT-Cantonese (CRTT-L-Cantonese), and the reading comprehension version of CRTT-Cantonese (CRTT-R- WF -Cantonese) across different sessions. Linear mixed-effect analysis revealed significant differences among the groups in CRTT-Cantonese tests. However, there were no significant difference between CRTT-L-Cantonese and CRTT-R- WF -Cantonese within the PWA, RHD and healthy control groups. Tukey post-hoc pairwise comparisons showed that PWA scored significantly lower than RHD and healthy control groups ( p  < 0.0001) in both CRTT-L-Cantonese and CRTT-R- WF -Cantonese, and the RHD group scored significantly lower than healthy control group only on the CRTT-R- WF -Cantonese. The results demonstrate that the CRTT-L-Cantonese and CRTT-R- WF -Cantonese differentiate language comprehension abilities among PWA, RHD and healthy control groups. Although the current findings did not show any diversion between reading and listening comprehension in RHD group, this group showed poorer performance in reading comprehension when compared to healthy controls. The latter findings may support the view that the right hemisphere contributes to reading comprehension in Chinese.

Current therapies for Fabry disease are based on reversing intracellular accumulation of globotriaosylceramide (Gb3) by enzyme replacement therapy (ERT) or chaperone-mediated stabilization of the defective enzyme, thereby alleviating lysosomal dysfunction. However, their effect in the reversal of end-organ damage, like kidney injury and chronic kidney disease, remains unclear. In this study, ultrastructural analysis of serial human kidney biopsies showed that long-term use of ERT reduced Gb3 accumulation in podocytes but did not reverse podocyte injury. Then, a CRISPR/Cas9-mediated α-galactosidase knockout podocyte cell line confirmed ERT-mediated reversal of Gb3 accumulation without resolution of lysosomal dysfunction. Transcriptome-based connectivity mapping and SILAC-based quantitative proteomics identified α-synuclein (SNCA) accumulation as a key event mediating podocyte injury. Genetic and pharmacological inhibition of SNCA improved lysosomal structure and function in Fabry podocytes, exceeding the benefits of ERT. Together, this work reconceptualizes Fabry-associated cell injury beyond Gb3 accumulation, and introduces SNCA modulation as a potential intervention, especially for patients with Fabry nephropathy.

According to the American Joint Cancer Committee, pT3 renal pelvic carcinoma is defined as tumor invading the renal parenchyma and/or peripelvic fat and is the largest pT category, with notable survival heterogeneity. Anatomical landmarks within the renal pelvis can be difficult to discern. Using glomeruli as a boundary to differentiate renal medulla invasion from renal cortex invasion, this study aimed to compare patient survival of pT3 renal pelvic urothelial carcinoma on the basis of the extent of renal parenchyma invasion and, thereafter, determine whether redefining pT2 and pT3 improves pT correlation with survival. Cases with primary renal pelvic urothelial carcinoma were identified through a review of pathology reports from nephroureterectomies completed at our institution from 2010 to 2019 (n = 145). Tumors were stratified by pT, pN, lymphovascular invasion, and invasion of the renal medulla versus invasion of the renal cortex and/or peripelvic fat. Overall survival between groups was compared using Kaplan-Meier survival models and Cox regression multivariate analysis. pT2 and pT3 tumors had similar 5-year overall survival, with multivariate analysis demonstrating an overlap between hazard ratios (HRs) for pT2 (HR, 2.20; 95% CI, 0.70-6.95) and pT3 (HR, 3.15; 95% CI, 1.63-6.09). pT3 tumors with peripelvic fat and/or renal cortex invasion had a 3.25-fold worse prognosis than pT3 tumors with renal medulla invasion alone. Furthermore, pT2 and pT3 tumors with only renal medulla invasion had similar overall survival, whereas pT3 tumors with peripelvic fat and/or renal cortex invasion had a worse prognosis (P = .00036). Reclassifying pT3 tumors with only renal medulla invasion as pT2 yielded greater separation between survival curves and HR. Thus, we recommend redefining pT2 renal pelvic carcinoma to include renal medulla invasion and restricting pT3 to peripelvic fat and/or renal cortex invasion to improve the prognostic accuracy of pT classification., (Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Background: A survey study on clinical practice not only provides insight into the implementation of knowledge, but also informs future investigations. There is a limited understanding of childhood apraxia of speech (CAS) in Cantonese speakers. This study examined the clinical practice of CAS in Hong Kong and discussed future directions of research for better evidence-based practice., Methods: Qualified Hong Kong pediatric speech-language pathologists (SLPs) completed the online questionnaire, which had a total of 48 questions regarding their knowledge of and experience with CAS in Cantonese speakers, including assessment, diagnosis, and treatment., Results: Seventy-seven responses were received from Hong Kong SLPs. Most of the SLPs (83.2%) rated their understanding of CAS as either "a little" or "fair". About half (53.2%) of the respondents had worked with children with CAS. No standardized assessment or objective/quantitative measures were used clinically. Instead, seven assessment tasks, including imitation of polysyllabic words and speech and language samples were used commonly. Perceptual judgment of clinical features is still the most popular approach for diagnosis, with a variety of lists in use. Of concern was that, in addition to using some evidence-based approaches, local SLPs treated CAS using approaches that have limited evidence, in the context of less treatment frequency, targeting both speech and language skills within the same session, and with only partial implementation of the approaches., Conclusions: The results suggest that the understanding of CAS among local SLPs requires attention. One reason for this is that evidence regarding the assessment, diagnosis, and treatment of Cantonese speakers with CAS is still limited. Future investigations are needed., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Wong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Expansion microscopy physically enlarges biological specimens to achieve nanoscale resolution using diffraction-limited microscopy systems 1 . However, optimal performance is usually reached using laser-based systems (for example, confocal microscopy), restricting its broad applicability in clinical pathology, as most centres have access only to light-emitting diode (LED)-based widefield systems. As a possible alternative, a computational method for image resolution enhancement, namely, super-resolution radial fluctuations (SRRF) 2,3 , has recently been developed. However, this method has not been explored in pathology specimens to date, because on its own, it does not achieve sufficient resolution for routine clinical use. Here, we report expansion-enhanced super-resolution radial fluctuations (ExSRRF), a simple, robust, scalable and accessible workflow that provides a resolution of up to 25 nm using LED-based widefield microscopy. ExSRRF enables molecular profiling of subcellular structures from archival formalin-fixed paraffin-embedded tissues in complex clinical and experimental specimens, including ischaemic, degenerative, neoplastic, genetic and immune-mediated disorders. Furthermore, as examples of its potential application to experimental and clinical pathology, we show that ExSRRF can be used to identify and quantify classical features of endoplasmic reticulum stress in the murine ischaemic kidney and diagnostic ultrastructural features in human kidney biopsies., (© 2023. The Author(s).)

Drawing on demands-resources theory, we develop and test a dual-path model to unpack the energizing and draining mechanisms, captured by leader need satisfaction and role conflict, through which servant leadership affects leader psychological strain and job performance. We further identify leader-leader exchange (LLX) as a critical resource moderator that can strengthen the energizing benefit and buffer against the draining cost of servant leadership behaviors. Using five-wave, multisource field data from 474 team leaders, 3,712 followers, and 97 superior leaders, we find support for the energizing benefit, in that servant leadership satisfied leader psychological needs, which subsequently reduced leader psychological strain. This energizing benefit was stronger when LLX was higher. In parallel, servant leaders experienced role conflict, which subsequently increased their psychological strain and deteriorated their job performance when LLX was lower. Overall, our research contributes to a fine-grained understanding of the double-edged effects of servant leadership on leaders and sheds light on how and when leaders can benefit from practicing servant leadership. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Purpose: Apraxia of speech (AOS) and childhood apraxia of speech (CAS) are motor-based speech disorders that have been well studied in Indo-European languages. There is limited understanding of these disorders in speakers of Sino-Tibetan languages, such as Chinese. The purpose of this study is to review methods used in research studies for the assessment and diagnosis of AOS and CAS in Chinese speakers., Method: This scoping review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines. Articles with a focus on AOS or CAS in Chinese speakers were systematically searched in seven English and six Chinese databases. Three reviewers performed independent screening, data extraction, and quality assessment after obtaining 100% agreement on the prescreening exercise. A qualitative analysis was conducted to rate the quality of diagnoses, ranging from high (Level I) to low (Level III), with Level IV assigned to studies for which the appropriate rating was unclear due to insufficient evidence., Results: Twenty-eight AOS articles and five CAS articles were identified. A variety of assessment and diagnostic methods were reported. No study of Chinese speakers with AOS or CAS received a rating of Level I. The highest level achieved was Level IIIa for both AOS and CAS studies., Conclusions: There is no reliable and valid test or method for the diagnosis of AOS or CAS in Chinese speakers. The current gold standard of diagnosis is based upon expert perceptual judgment. Further single-language and cross-linguistic investigations of AOS and CAS and the future development of assessment and diagnostic methods are recommended.

A role of CD4+ T cells during the progression from nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis (NASH) has been suggested, but which polarization state of these cells characterizes this progression and the development of fibrosis remain unclear. In addition, a gut-liver axis has been suggested to play a role in NASH, but the role of CD4+ T cells in this axis has just begun to be investigated. Combining single-cell RNA sequencing and multiple-parameter flow cytometry, we provide the first cell atlas to our knowledge focused on liver-infiltrating CD4+ T cells in patients with NAFLD and NASH, showing that NASH is characterized by a population of multicytokine-producing CD4+ T cells. Among these cells, only those with a Th17 polarization state were enriched in patients with advanced fibrosis. In parallel, we observed that Bacteroides appeared to be enriched in the intestine of NASH patients and to correlate with the frequency of multicytokine-producing CD4+ T cells. In short, we deliver a CD4+ T cell atlas of NAFLD and NASH, providing the rationale to target CD4+ T cells with a Th17 polarization state to block fibrosis development. Finally, our data offer an early indication to test whether multicytokine-producing CD4+ T cells are part of the gut-liver axis characterizing NASH.

Purpose: The current study investigated the therapeutic potential of transcranial direct current stimulation (tDCS) on speech intelligibility, speech-related physiological and vocal functions among post-stroke dysarthric patients., Method: Nine chronic post-stroke dysarthric patients were randomly assigned to the stimulation or sham group. The stimulation group received 2mA of anodal tDCS over the left inferior primary motor cortex for 15 minutes, while the sham group received 30s of stimulation under the same settings. All the participants received 10 daily 15 minutes of individualized speech therapy targeting their dominant phonological process or phonemes with the greatest difficulty. The outcome measures included (1) perceptual analysis of single words, passage reading and diadochokinetic rate, (2) acoustic analysis of a sustained vowel, and (3) kinematic analysis of rapid syllable repetitions and syllable production in sentence, conducted before and after the treatment., Results: The results revealed that both the stimulation and sham groups had improved perceptual speech intelligibility at the word level, reduced short rushes of speech during passage reading, improved rate during alternating motion rate, AMR-kha1, and improved articulatory kinematics in AMR-tha1 and syllables /tha1/ and /kha1/ production in sentence. Compared to the sham group, the stimulation group showed significant improvement in articulatory kinematics in AMR-kha1 and syllable /kha1/ production in sentence. The findings also showed that anodal stimulation led to reduced shimmer value in sustained vowel /a/ phonation, positive changes in articulatory kinematics in AMR-tha1 and syllables /pha1/ and /kha1/ production in sentence at the post treatment measure. In addition to positive effects on articulatory control, reduced perturbation of voice amplitude documented in the stimulation group post treatment suggests possible tDCS effects on the vocal function., Conclusions: The current study documented the beneficial effects of anodal tDCS over the primary motor cortex on speech production and suggested that combined tDCS and speech therapy may promote recovery from post-stroke dysarthria., Competing Interests: The authors have declared that no competing interests exist.

Background: Childhood apraxia of speech (CAS) is a motor-based speech sound disorder (SSD) with a core impairment in the planning and programming of spatiotemporal parameters of speech movement sequences. CAS may cause deficits in both segmental and suprasegmental components of speech, and it can severely affect children's ability to speak intelligibly and communicate effectively and impact their quality of life. Assessment tasks, such as the maximum performance tasks (MPT) and Syllable Repetition Task (SRT), examine children's segmental sequencing skills to assist with the diagnosis of CAS. In Hong Kong, although the MPT and SRT have been used clinically to diagnose CAS in Cantonese-speaking children, their validity has not been reported. There is an urgent need for such investigations. Suprasegmentally, lexical stress errors have been reported as a consensual feature and to aid in the diagnosis of CAS. However, there are challenges in diagnosing CAS in children who speak tonal languages like Cantonese. A recent study has reported lexical tone errors in Cantonese-speaking children with CAS. Furthermore, deficits in pitch-variation skills were found in Cantonese-speaking children with CAS using a tone sequencing task (TST). It is hypothesized that there is a universal deficit in pitch-variation skills among tonal and nontonal language speakers with CAS. Further investigations of pitch-variation skills using the TST in Cantonese-speaking children with CAS may shed light on suprasegmental deficits in tonal languages and contribute to the development of a valid diagnostic tool for CAS in children who speak other tonal languages, such as Vietnamese, Thai, and Mandarin., Objective: This study aims to examine the diagnostic potential of the MPT, SRT, and TST in diagnosing Cantonese-speaking children with CAS and to investigate pitch-variation skills in Cantonese-speaking children with and without CAS., Methods: A total of 25 children with CAS and 3 groups of age- and gender-matched controls (non-CAS SSD only group, non-CAS SSD co-occurring with language impairment group, and typical development group) will be recruited. All participants will perform the MPT, SRT, and TST measures. Their performances on these tools will be perceptually judged and acoustically measured., Results: Data collection will last from January 1, 2022, to October 30, 2023. As of August 2022, the project has recruited 4 children in the CAS group, 21 children in the non-CAS SSD group, 4 children in the speech and language impairment group, and 53 children in the typical development group., Conclusions: It is anticipated that Cantonese-speaking children with CAS will have poorer pitch-variation skills than the control groups and that the MPT, SRT, and TST will be appropriate diagnostic tools for identifying CAS in Cantonese-speaking children. The project will benefit the field of speech-language pathology locally and internationally, with short- and long-term impacts., International Registered Report Identifier (irrid): DERR1-10.2196/40465., (©Min Ney Wong, Eddy C H Wong, Shelley L Velleman. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 04.10.2022.)

Background: Aneurysmal bone cysts (ABCs) are benign, locally aggressive neoplasms that typically affect patients during their first two decades of life. Curettage with or without bone grafting or adjuvants is the current standard treatment; however, other surgical and medical treatments, such as sclerotherapy, have been reported. Treatment options for cervical spine ABCs are more limited because the proximity of ABCs to critical structures leads to greater risk of spontaneous or treatment-related adverse events, including death., Objective: To retrospectively review all children and young adults with cervical spine ABCs treated with doxycycline sclerotherapy at one referral center to assess its viability as a standalone treatment., Materials and Methods: We retrospectively reviewed the clinical notes and imaging of 16 patients treated with doxycycline sclerotherapy for pathologically proven cervical spine ABCs at our institution between May 2008 and March 2021. All patients underwent image-guided percutaneous doxycycline sclerotherapy to ablate the ABC and stimulate bone formation. We assessed clinical outcomes through chart review and described post-treatment imaging outcomes using modified Neer scoring., Results: Of the 16 total children and young adults treated, 2 were lost to follow-up, leaving 14 patients with a median age of 14.5 years. Twelve of these 14 patients were successfully treated with doxycycline sclerotherapy for a success rate of 86%. One patient experienced one treatment-related complication (Society of Interventional Radiology [SIR] adverse event classification D), before ultimately being successfully treated. Doxycycline treatment failed in two patients, who then underwent surgical management. Post-treatment imaging of successfully treated cases had a mean modified Neer score of 1.3, whereas post-treatment imaging in failed cases had a mean score of 3.5., Conclusion: Doxycycline sclerotherapy is a viable standalone treatment for cervical spine ABCs because it is safe and effective while avoiding the morbidity associated with open surgical treatments., (© 2022. The Author(s).)

Staphylococcus aureus is frequently detected in patients with sepsis and thus represents a major health burden worldwide. CD4+ T helper cells are involved in the immune response to S. aureus by supporting antibody production and phagocytosis. In particular, Th1 and Th17 cells secreting IFN-γ and IL-17A, are involved in the control of systemic S. aureus infections in humans and mice. To investigate the role of T cells in severe S. aureus infections, we established a mouse sepsis model in which the kidney was identified to be the organ with the highest bacterial load and abundance of Th17 cells. In this model, IL-17A but not IFN-γ was required for bacterial control. Using Il17aCre × R26YFP mice we could show that Th17 fate cells produce Th17 and Th1 cytokines, indicating a high degree of Th17 cell plasticity. Single cell RNA-sequencing of renal Th17 fate cells uncovered their heterogeneity and identified a cluster with a Th1 expression profile within the Th17 cell population, which was absent in mice with T-bet/Tbx21-deficiency in Th17 cells (Il17aCre x R26eYFP x Tbx21-flox). Blocking Th17 to Th1 transdifferentiation in Th17 fate cells in these mice resulted in increased S. aureus tissue loads. In summary, we highlight the impact of Th17 cells in controlling systemic S. aureus infections and show that T-bet expression by Th17 cells is required for bacterial clearance. While targeting the Th17 cell immune response is an important therapeutic option in autoimmunity, silencing Th17 cells might have detrimental effects in bacterial infections., Competing Interests: The authors have declared that no competing interests exist.

Extrapulmonary manifestations of COVID-19 have gained attention due to their links to clinical outcomes and their potential long-term sequelae 1 . Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) displays tropism towards several organs, including the heart and kidney. Whether it also directly affects the liver has been debated 2,3 . Here we provide clinical, histopathological, molecular and bioinformatic evidence for the hepatic tropism of SARS-CoV-2. We find that liver injury, indicated by a high frequency of abnormal liver function tests, is a common clinical feature of COVID-19 in two independent cohorts of patients with COVID-19 requiring hospitalization. Using autopsy samples obtained from a third patient cohort, we provide multiple levels of evidence for SARS-CoV-2 liver tropism, including viral RNA detection in 69% of autopsy liver specimens, and successful isolation of infectious SARS-CoV-2 from liver tissue postmortem. Furthermore, we identify transcription-, proteomic- and transcription factor-based activity profiles in hepatic autopsy samples, revealing similarities to the signatures associated with multiple other viral infections of the human liver. Together, we provide a comprehensive multimodal analysis of SARS-CoV-2 liver tropism, which increases our understanding of the molecular consequences of severe COVID-19 and could be useful for the identification of organ-specific pharmacological targets., (© 2022. The Author(s).)